FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Szulkin, R Whitington, T Eklund, M Aly, M Eeles, RA Easton, D Kote-Jarai, Z Al Olama, AA Benlloch, S Muir, K Giles, GG Southey, MC Fitzgerald, LM Henderson, BE Schumacher, F Haiman, CA Schleutker, J Wahlfors, T Tammela, TLJ Nordestgaard, BG Key, TJ Travis, RC Neal, DE Donovan, JL Hamdy, FC Pharoah, P Pashayan, N Khaw, KT Stanford, JL Thibodeau, SN McDonnell, SK Schaid, DJ Maier, C Vogel, W Luedeke, M Herkommer, K Kibel, AS Cybulski, C Lubinski, J Kluzniak, W Cannon-Albright, L Brenner, H Butterbach, K Stegmaier, C Park, JY Sellers, T Lim, HY Slavov, C Kaneva, R Mitev, V Batra, J Clements, JA Spurdle, A Teixeira, MR Paulo, P Maia, S Pandha, H Michael, A Kierzek, A Gronberg, H Wiklund, F AF Szulkin, Robert Whitington, Thomas Eklund, Martin Aly, Markus Eeles, Rosalind A. Easton, Douglas Kote-Jarai, ZSofia Al Olama, Ali Amin Benlloch, Sara Muir, Kenneth Giles, Graham G. Southey, Melissa C. Fitzgerald, Liesel M. Henderson, Brian E. Schumacher, Fredrick Haiman, Christopher A. Schleutker, Johanna Wahlfors, Tiina Tammela, Teuvo L. J. Nordestgaard, Borge G. Key, Tim J. Travis, Ruth C. Neal, David E. Donovan, Jenny L. Hamdy, Freddie C. Pharoah, Paul Pashayan, Nora Khaw, Kay-Tee Stanford, Janet L. Thibodeau, Stephen N. McDonnell, Shannon K. Schaid, Daniel J. Maier, Christiane Vogel, Walther Luedeke, Manuel Herkommer, Kathleen Kibel, Adam S. Cybulski, Cezary Lubinski, Jan Kluzniak, Wojciech Cannon-Albright, Lisa Brenner, Hermann Butterbach, Katja Stegmaier, Christa Park, Jong Y. Sellers, Thomas Lim, Hui-Yi Slavov, Chavdar Kaneva, Radka Mitev, Vanio Batra, Jyotsna Clements, Judith A. Spurdle, Amanda Teixeira, Manuel R. Paulo, Paula Maia, Sofia Pandha, Hardev Michael, Agnieszka Kierzek, Andrzej Gronberg, Henrik Wiklund, Fredrik CA Australian Prostate Canc BioResour PRACTICAL Consortium TI Prediction of Individual Genetic Risk to Prostate Cancer Using a Polygenic Score SO PROSTATE LA English DT Article DE prostate cancer; polygenic risk score; risk prediction ID SUSCEPTIBILITY LOCI; MUTATION CARRIERS; BREAST; BRCA2; RECLASSIFICATION; VARIANTS; DISEASES; COHORT; IMPACT AB BACKGROUND. Polygenic risk scores comprising established susceptibility variants have shown to be informative classifiers for several complex diseases including prostate cancer. For prostate cancer it is unknown if inclusion of genetic markers that have so far not been associated with prostate cancer risk at a genome-wide significant level will improve disease prediction. METHODS. We built polygenic risk scores in a large training set comprising over 25,000 individuals. Initially 65 established prostate cancer susceptibility variants were selected. After LD pruning additional variants were prioritized based on their association with prostate cancer. Six-fold cross validation was performed to assess genetic risk scores and optimize the number of additional variants to be included. The final model was evaluated in an independent study population including 1,370 cases and 1,239 controls. RESULTS. The polygenic risk score with 65 established susceptibility variants provided an area under the curve (AUC) of 0.67. Adding an additional 68 novel variants significantly increased the AUC to 0.68 (P-0012) and the net reclassification index with 0.21 (P-8.5 E-08). All novel variants were located in genomic regions established as associated with prostate cancer risk. CONCLUSIONS. Inclusion of additional genetic variants from established prostate cancer susceptibility regions improves disease prediction. (C) 2015 Wiley Periodicals, Inc. C1 [Szulkin, Robert; Whitington, Thomas; Eklund, Martin; Aly, Markus; Gronberg, Henrik; Wiklund, Fredrik] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. [Aly, Markus] Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden. [Eeles, Rosalind A.; Kote-Jarai, ZSofia] Inst Canc Res, London SW3 6JB, England. [Eeles, Rosalind A.] Royal Marsden Natl Hlth Serv NHS Fdn Trust, London, England. [Eeles, Rosalind A.] Royal Marsden Natl Hlth Serv NHS Fdn Trust, Sutton, Surrey, England. [Easton, Douglas; Al Olama, Ali Amin; Benlloch, Sara] Univ Cambridge, Strangeways Lab, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. [Muir, Kenneth] Univ Manchester, Inst Populat Hlth, Manchester, Lancs, England. [Muir, Kenneth] Univ Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England. [Giles, Graham G.; Fitzgerald, Liesel M.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Giles, Graham G.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic 3010, Australia. [Southey, Melissa C.] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic 3010, Australia. [Henderson, Brian E.; Schumacher, Fredrick; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Schleutker, Johanna] Univ Turku, Inst Biomed Kiinamyllynkatu 10, Dept Med Biochem & Genet, SF-20500 Turku, Finland. [Schleutker, Johanna; Wahlfors, Tiina] Univ Tampere, BioMediTech, FIN-33101 Tampere, Finland. [Schleutker, Johanna; Wahlfors, Tiina] FimLab Labs, Tampere, Finland. [Tammela, Teuvo L. J.] Univ Tampere, Dept Urol, Tampere Univ Hosp, FIN-33101 Tampere, Finland. [Tammela, Teuvo L. J.] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. [Nordestgaard, Borge G.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Herlev, Denmark. [Nordestgaard, Borge G.] Univ Copenhagen, Fac Hlth & Med Sci, DK-1168 Copenhagen, Denmark. [Key, Tim J.; Travis, Ruth C.] Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol, Oxford, England. [Neal, David E.] Univ Cambridge, Dept Oncol, Addenbrookes Hosp, Cambridge CB2 1TN, England. [Neal, David E.] Li Ka Shing Ctr, Canc Res UK Cambridge Res Inst, Cambridge, England. [Donovan, Jenny L.] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England. [Hamdy, Freddie C.] Univ Oxford, John Radcliffe Hosp, Fac Med Sci, Nuffield Dept Surg Sci, Oxford OX3 9DU, England. [Pharoah, Paul; Pashayan, Nora] Univ Cambridge, Dept Oncol, Strangeways Res Lab, Ctr Canc Genet Epidemiol, Cambridge, England. [Pashayan, Nora] UCL, London, England. [Khaw, Kay-Tee] Univ Cambridge, Clin Gerontol Unit, Cambridge, England. [Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Thibodeau, Stephen N.; McDonnell, Shannon K.; Schaid, Daniel J.] Mayo Clin, Rochester, MN USA. [Maier, Christiane; Luedeke, Manuel] Univ Hosp Ulm, Dept Urol, Ulm, Germany. [Vogel, Walther] Univ Hosp Ulm, Inst Human Genet, Ulm, Germany. [Herkommer, Kathleen] Techn Univ Muenchen, Klinikum Rechts Isar, Dept Urol, Munich, Germany. [Kibel, Adam S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Urol Surg, Boston, MA 02115 USA. [Cybulski, Cezary; Lubinski, Jan; Kluzniak, Wojciech] Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland. [Cannon-Albright, Lisa] Univ Utah, Sch Med, Dept Med, Div Genet Epidemiol, Salt Lake City, UT USA. [Cannon-Albright, Lisa] George E Wahlen Dept Vet Affairs Med Ctr, Salt Lake City, UT USA. [Brenner, Hermann; Butterbach, Katja] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Brenner, Hermann] German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany. [Brenner, Hermann] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany. [Stegmaier, Christa] Saarland Canc Registry, Saarbrucken, Germany. [Park, Jong Y.; Sellers, Thomas] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA. [Lim, Hui-Yi] H Lee Moffitt Canc Ctr & Res Inst, Biostat Program, Tampa, FL USA. [Slavov, Chavdar] Med Univ Sofia, Dept Urol, Sofia, Bulgaria. [Slavov, Chavdar] Med Univ Sofia, Alexandrovska Univ Hosp, Sofia, Bulgaria. [Kaneva, Radka; Mitev, Vanio] Med Univ Sofia, Mol Med Ctr, Dept Med Chem & Biochem, Sofia, Bulgaria. [Batra, Jyotsna; Clements, Judith A.] Queensland Univ Technol, Australian Prostate Canc Res Centre Qld, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia. [Batra, Jyotsna; Clements, Judith A.] Queensland Univ Technol, Sch Biomed Sci, Brisbane, Qld 4001, Australia. [Australian Prostate Canc BioResour] Australian Prostate Canc BioResource, Brisbane, Qld, Australia. [Spurdle, Amanda] Queensland Inst Med Res, Mol Canc Epidemiol Lab, Brisbane, Qld 4006, Australia. [Teixeira, Manuel R.; Paulo, Paula; Maia, Sofia] Portuguese Oncol Inst, Dept Genet, Oporto, Portugal. [Teixeira, Manuel R.] Univ Porto, Biomed Sci Inst ICBAS, P-41000 Oporto, Portugal. Univ Surrey, Guildford GU2 5XH, Surrey, England. RP Szulkin, R (reprint author), Karolinska Inst, Dept Med Epidemiol & Biostat, Box 281, SE-17177 Stockholm, Sweden. EM robert.szulkin@ki.se RI Teixeira, Manuel/E-4885-2011; Paulo, Paula/F-1441-2016; Batra, Jyotsna/B-4130-2011; Brenner, Hermann/B-4627-2017; OI Teixeira, Manuel/0000-0002-4896-5982; Paulo, Paula/0000-0001-8387-2127; Brenner, Hermann/0000-0002-6129-1572; Kierzek, Andrzej/0000-0002-2605-9057; Eeles, Rosalind/0000-0002-3698-6241; albright, lisa/0000-0003-2602-3668; Giles, Graham/0000-0003-4946-9099; Clements, Judith/0000-0001-6026-1964 FU Cancer Research UK [10124, 14136]; Medical Research Council [G0401527, G1000143] NR 25 TC 7 Z9 7 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-4137 EI 1097-0045 J9 PROSTATE JI Prostate PD SEP 15 PY 2015 VL 75 IS 13 BP 1467 EP 1474 DI 10.1002/pros.23037 PG 8 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA CP2MN UT WOS:000359711300012 PM 26177737 ER PT J AU Fletcher, K Parker, G Paterson, A Fava, M Iosifescu, D Pizzagalli, DA AF Fletcher, Kathryn Parker, Gordon Paterson, Amelia Fava, Maurizio Iosifescu, Dan Pizzagalli, Diego A. TI Anhedonia in melancholic and non-melancholic depressive disorders SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Melancholic; Non-melancholic; Depression; Anhedonia; Reward responsiveness; Motivation ID HAMILTON PLEASURE SCALE; REWARD RESPONSIVENESS; HEDONIC CAPACITY; ENDOGENOMORPHIC DEPRESSION; PSYCHOMETRIC EVALUATION; MAJOR DEPRESSION; SIGNAL-DETECTION; DOPAMINE; STRESS; MODEL AB Background: Anhedonia represents a core symptom of major depression and may be a potential marker for melancholia. However, current understanding of this construct in depressive sub types is limited. Method: Participants were recruited from the Black Dog Institute (Sydney) arid Massachusetts General Hospital (Boston). Diagnostic groups were derived on the basis of agreement between clinician and DSM-IV diagnosis from structured interviews. Currently depressed unipolar melancholic, non melancholic and healthy control participants were administered a probabilistic reward task (PRT) to assess a behavioural correlate of anhedonia-blunted reward based learning. Self reported measures of anhedonia, approach and avoidance motivation were completed by the Sydney sample. Results: Relative to healthy controls and non-melancholic participants, melancholic depressed participants had reduced response bias, highlighting blunted reward teaming. Moreover, although non-melancholic participants were characterized by a delayed response bias, melancholic depressed participants Failed to develop a bias throughout blocks. Response bias showed 110 associations with self-report measures of hedonic tone in depressed participants. Positive associations were observed between response bias, approach and avoidance motivation in non-melancholic participants only. Limitations: Possible medication, fatigue and anxiety effects were not controlled; small sample sizes; inclusion criteria may have excluded those with severe melancholia and led to underestimation of group differences. Conclusions: Melancholia is characterised by a reduced ability to modulate behaviour as a function of reward, and the motivational salience of rewarding stimuli may differ across depressive sub-types. Results support the view that melancholia is a distinct sub-type. Further exploration of reward system functioning in depressive sub-types is warranted. (C) 2015 Elsevier B.V. All rights reserved. C1 [Fletcher, Kathryn; Parker, Gordon; Paterson, Amelia] Univ New S Wales, Sch Psychiat, Sydney, NSW 2052, Australia. [Fletcher, Kathryn; Parker, Gordon; Paterson, Amelia] Black Dog Inst, Sydney, NSW, Australia. [Fletcher, Kathryn] Ctr Psychol & Relationship Counselling, Melbourne, Vic, Australia. [Fava, Maurizio; Pizzagalli, Diego A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fava, Maurizio] Harvard Univ, Sch Med, Boston, MA USA. [Iosifescu, Dan] Mt Sinai Hosp, New York, NY 10029 USA. [Pizzagalli, Diego A.] McLean Hosp, Belmont, MA 02178 USA. RP Fletcher, K (reprint author), Ctr Psychol & Relationship Counselling, Bell City Suite East 02,205 Bell St, Preston, Vic 3072, Australia. EM kat303@hotmail.com OI Parker, Gordon/0000-0003-3424-5519 FU NHMRC [1037196]; NIMH [R01 MH068376, MH101521] FX Funding for the Sydney site component of this study was provided by NHMRC Program Grant (1037196). The NHMRC had no further role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the manuscript for publication.; Dr. Pizzagalli was partially supported by NIMH Grants R01 MH068376 and MH101521. NR 58 TC 5 Z9 5 U1 5 U2 18 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 SEP 15 PY 2015 VL 184 BP 81 EP 88 DI 10.1016/j.jad.2015.05.028 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CN6OR UT WOS:000358554600010 PM 26074016 ER PT J AU Rachmin, I Amsalem, E Golomb, E Beeri, R Gilon, D Fang, PF Nechushtan, H Kay, G Guo, M Yiqing, PL Foo, RSY Fisher, DE Razin, E Tshori, S AF Rachmin, Inbal Amsalem, Eden Golomb, Eliahu Beeri, Ronen Gilon, Dan Fang, Pengfei Nechushtan, Hovav Kay, Gillian Guo, Min Yiqing, Peter Li Foo, Roger S. -Y. Fisher, David E. Razin, Ehud Tshori, Sagi TI FHL2 switches MITF from activator to repressor of Erbin expression during cardiac hypertrophy SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE MITF; FHL2; Erbin; Activator; Repressor; Gene regulation ID GENE-EXPRESSION; MICROPHTHALMIA MI; HEART-FAILURE; CO-REPRESSOR; MAST-CELLS; LIM DOMAIN; PROTEIN; MUTATIONS; LOCUS; INTERACTS AB Background: Congestive heart failure (CHF) is a significant health care burden in developed countries. However, the molecular events leading from cardiac hypertrophy to CHF are unclear and preventive therapeutic approaches are limited. We have previously described that microphthalmia-associated transcription factor (MITF) is a key regulator of cardiac hypertrophy, but its cardiac targets are still uncharacterized. Methods and results: Gene array analysis of hearts from MITF-mutated mice indicated that ErbB2 interacting protein (Erbin) is a candidate target gene for MITF. We have recently demonstrated that Erbin is decreased in human heart failure and plays a role as a negative modulator of pathological cardiac hypertrophy. Here we show that Erbin expression is regulated by MITF. Under basal conditions MITF activates Erbin expression by direct binding to its promoter. However, under beta-adrenergic stimulation Erbin expression is decreased only in wild type mice, but not in MITF-mutated mice. Yeast two-hybrid screening, using MITF as bait, identified an interaction with the cardiac-predominant four-and-a-half LIM domain protein 2 (FHL2), which was confirmed by co-immunoprecipitation in both mouse and human hearts. Upon mu-adrenergic stimulation, FHL2 and MITF bind Erbin promoter as a complex and repress MITF-directed Erbin expression. Overexpression of FHL2 alone had no effect on Erbin expression, but in the presence of MITF, Erbin expression was decreased. FHL2-MITF association was also increased in biopsies of heart failure patients. Conclusion: MITF unexpectedly regulates both the activation and the repression of Erbin expression. This ligand mediated fine tuning of its gene expression could be an important mechanism in the process of cardiac hypertrophy and heart failure. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Rachmin, Inbal; Amsalem, Eden; Kay, Gillian; Razin, Ehud] Hebrew Univ Jerusalem, Sch Med, Inst Med Res Israel Canada, Dept Biochem & Mol Biol, IL-91120 Jerusalem, Israel. [Golomb, Eliahu] Shaare Zedek Med Ctr, Dept Pathol, IL-91031 Jerusalem, Israel. [Beeri, Ronen; Gilon, Dan] Hadassah Hebrew Univ, Med Ctr, Inst Heart, IL-91120 Jerusalem, Israel. [Fang, Pengfei; Guo, Min] Scripps Res Inst, Dept Canc Biol, Jupiter, FL 33458 USA. [Nechushtan, Hovav] Hadassah Hebrew Univ, Med Ctr, Sharett Inst Oncol, IL-91120 Jerusalem, Israel. [Yiqing, Peter Li; Foo, Roger S. -Y.] Natl Univ Singapore, Ctr Translat Med, Cardiovasc Res Inst, Singapore 117599, Singapore. [Fisher, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr,Dept Dermatol, Boston, MA 02129 USA. [Tshori, Sagi] Hadassah Hebrew Univ, Med Ctr, Dept Nucl Med, IL-91120 Jerusalem, Israel. RP Foo, RSY (reprint author), Natl Univ Singapore, Ctr Translat Med, Cardiovasc Res Inst, Singapore 117599, Singapore. EM mdcrfsy@nus.edu.sg; ehudr@ekmd.huji.ac.il RI Fang, Pengfei/O-3696-2015; Kay, Gillian/F-3474-2014 OI Fang, Pengfei/0000-0002-3448-5494; Kay, Gillian/0000-0003-0966-2388 FU Israel Science Foundation [1925/12, 115/2013]; United States Binational Science Foundation [2007220]; National Research Foundation of Singapore; NIH [R01 AR043369-18, P01 CA163222]; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation FX This research was supported by the Israel Science Foundation [1925/12 to S.T and 115/2013 to E.R.], the United States Binational Science Foundation [2007220 to E.R. and D.E.F.]; the National Research Foundation of Singapore [HUJ-CREATE to E.R.], by the NIH [R01 AR043369-18 and P01 CA163222 to D.E.F], and by a grant from the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation [to D.E.F.]. NR 32 TC 2 Z9 2 U1 0 U2 14 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD SEP 15 PY 2015 VL 195 BP 85 EP 94 DI 10.1016/j.ijcard.2015.05.108 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CL0DK UT WOS:000356609100023 PM 26025865 ER PT J AU DuBois, CM Lopez, OV Beale, EE Healy, BC Boehm, JK Huffman, JC AF DuBois, Christina M. Lopez, Oriana Vesga Beale, Eleanor E. Healy, Brian C. Boehm, Julia K. Huffman, Jeff C. TI Relationships between positive psychological constructs and health outcomes in patients with cardiovascular disease: A systematic review SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Review DE Optimism; Positive affect; Well-being; Cardiovascular disease; Coronary artery disease; Systematic review ID CORONARY-HEART-DISEASE; QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; BYPASS GRAFT-SURGERY; MYOCARDIAL-INFARCTION; DISPOSITIONAL OPTIMISM; CLINICAL-TRIALS; PROGNOSTIC ASSOCIATION; DEPRESSIVE SYMPTOMS; ARTERY-DISEASE AB Depression and anxiety are well-known to be associated with adverse health outcomes in cardiac patients. However, there has been less work synthesizing the effects of positive psychological constructs (e.g., optimism) on health-related outcomes in cardiac patients. We completed a systematic review of prospective observational studies using established guidelines. A search of PubMed and PsycINFO databases from inception to January 2014 was used to identify articles. To be eligible, studies were required to assess effects of a positive psychological construct on subsequent health-related outcomes (including mortality, rehospitalizations, self-reported health status) in patients with established heart disease. Exploratory random effects' meta-analyses were performed on the subset of studies examining mortality or rehospitalizations. Seventy-seven analyses from 30 eligible studies (N = 14,624) were identified. Among studies with 100 or more participants, 65.0% of all analyses and 64.7% of analyses adjusting for one or more covariates reported a significant (p < .05) association between positive psychological constructs and subsequent health outcomes. An exploratory meta-analysis of 11 studies showed that positive constructs were associated with reduced rates of rehospitalization or mortality in unadjusted (odds ratio = .87; 95% confidence interval [.83, .92]; p < .001) and adjusted analyses (odds ratio = .89; 95% confidence interval [.84, .91]; p < .001); there was little suggestion of publication bias. Among cardiac patients, positive psychological constructs appear to be prospectively associated with health outcomes in most but not all studies. Additional work is needed to identify which constructs are most important to cardiac health, and whether interventions can cultivate positive attributes and improve clinical outcomes. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [DuBois, Christina M.; Lopez, Oriana Vesga; Beale, Eleanor E.; Huffman, Jeff C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Lopez, Oriana Vesga; Healy, Brian C.] Harvard Univ, Sch Med, Boston, MA USA. [Healy, Brian C.; Huffman, Jeff C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Boehm, Julia K.] Chapman Univ, Dept Psychol, Orange, CA USA. RP Huffman, JC (reprint author), Massachusetts Gen Hosp, 55 Fruit St Warren 1220D, Boston, MA 02114 USA. EM jhuffman@partners.org FU National Heart, Lung, and Blood Institute of the National Institutes of Health [R01HL113272] FX This work was supported in part by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number R01HL113272 to JH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 77 TC 13 Z9 13 U1 3 U2 29 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD SEP 15 PY 2015 VL 195 BP 265 EP 280 DI 10.1016/j.ijcard.2015.05.121 PG 16 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CL0DK UT WOS:000356609100058 PM 26048390 ER PT J AU Hammerstad, SS Grock, SF Lee, HJ Hasham, A Sundaram, N Tomer, Y AF Hammerstad, Sara Salehi Grock, Shira Frankel Lee, Hanna J. Hasham, Alia Sundaram, Nina Tomer, Yaron TI Diabetes and hepatitis C: a two-way association SO FRONTIERS IN ENDOCRINOLOGY LA English DT Review DE type 1 diabetes; type 2 diabetes; hepatitis C virus; hepatitis C; insulin resistance; interferon alpha; hepatocellular carcinoma; outcomes; treatment ID NECROSIS-FACTOR-ALPHA; BETA-CELL FUNCTION; SUSTAINED VIROLOGICAL RESPONSE; INSULIN-RECEPTOR SUBSTRATE-1; CHRONIC LIVER-DISEASE; VIRUS CORE PROTEIN; ENDOPLASMIC-RETICULUM STRESS; GENOTYPE-SPECIFIC MECHANISMS; CHRONIC VIRAL-HEPATITIS; REGULATORY T-CELLS AB Diabetes and hepatitis C infection are both prevalent diseases worldwide, and are associated with increased morbidity and mortality. Most studies, but not all, have shown that patients with chronic hepatitis C are more prone to develop type 2 diabetes (T2D) compared to healthy controls, as well as when compared to patients with other liver diseases, including hepatitis B. Furthermore, epidemiological studies have revealed that patients with T2D may also be at higher risk for worse outcomes of their hepatitis C infection, including reduced rate of sustained virological response, progression to fibrosis and cirrhosis, and higher risk for development of hepatocellular carcinoma. Moreover, hepatitis C infection and mainly its treatment, interferon a, can trigger the development of type 1 diabetes. In this review, we discuss the existing data on this two-way association between diabetes and hepatitis C infection with emphasis on possible mechanisms. It remains to be determined whether the new curative therapies for chronic hepatitis C will improve outcomes in diabetic hepatitis C patients, and conversely whether treatment with Metformin will reduce complications from hepatitis C virus infection. We propose an algorithm for diabetes screening and follow-up in hepatitis C patients. C1 [Hammerstad, Sara Salehi; Grock, Shira Frankel; Lee, Hanna J.; Hasham, Alia; Sundaram, Nina; Tomer, Yaron] Icahn Sch Med Mt Sinai, Dept Med, Div Endocrinol, Box 1055,One Gustave L Levy Pl, New York, NY 10029 USA. [Hammerstad, Sara Salehi] Oslo Univ Hosp Ulleval, Dept Pediat, Oslo, Norway. [Tomer, Yaron] James J Peters VA Med Ctr, Bronx, NY USA. RP Tomer, Y (reprint author), Icahn Sch Med Mt Sinai, Div Endocrinol, Box 1055,One Gustave L Levy Pl, New York, NY 10029 USA. EM yaron.tomer@mssm.edu FU NIDDK [DK061659, DK067555, DK073681]; Helse Sor-Ost FX Supported by DK061659, DK067555, and DK073681 from NIDDK and Helse Sor-Ost. We wish to thank Dr. Emily Gallagher for helpful discussions. NR 217 TC 3 Z9 3 U1 0 U2 0 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-2392 J9 FRONT ENDOCRINOL JI Front. Endocrinol. PD SEP 14 PY 2015 VL 6 AR 134 DI 10.3389/fendo.2015.00134 PG 19 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DP4SF UT WOS:000378485800001 PM 26441826 ER PT J AU Gomez, H Kautza, B Escobar, D Nassour, I Luciano, J Botero, AM Gordon, L Martinez, S Holder, A Ogundele, O Loughran, P Rosengart, MR Pinsky, M Shiva, S Zuckerbraun, BS AF Gomez, Hernando Kautza, Benjamin Escobar, Daniel Nassour, Ibrahim Luciano, Jason Botero, Ana Maria Gordon, Lisa Martinez, Silvia Holder, Andre Ogundele, Olufunmilayo Loughran, Patricia Rosengart, Matthew R. Pinsky, Michael Shiva, Sruti Zuckerbraun, Brian S. TI Inhaled Carbon Monoxide Protects against the Development of Shock and Mitochondrial Injury following Hemorrhage and Resuscitation SO PLOS ONE LA English DT Article ID HEME OXYGENASE-1; TRANSCRIPTIONAL CONTROL; CELLULAR RESPIRATION; LUNG INJURY; BIOGENESIS; LIVER; INHALATION; MODEL; INHIBITION; MECHANISM AB Aims Currently, there is no effective resuscitative adjunct to fluid and blood products to limit tissue injury for traumatic hemorrhagic shock. The objective of this study was to investigate the role of inhaled carbon monoxide (CO) to limit inflammation and tissue injury, and specifically mitochondrial damage, in experimental models of hemorrhage and resuscitation. Results Inhaled CO (250 ppm for 30 minutes) protected against mortality in severe murine hemorrhagic shock and resuscitation (HS/R) (20% vs. 80%; P < 0.01). Additionally, CO limited the development of shock as determined by arterial blood pH (7.25 +/- 0.06 vs. 7.05 +/- 0.05; P < 0.05), lactate levels (7.2 +/- 5.1 vs 13.3 +/- 6.0; P < 0.05), and base deficit (13 +/- 3.0 vs 24 +/- 3.1; P < 0.05). A dose response of CO (25-500 ppm) demonstrated protection against HS/R lung and liver injury as determined by MPO activity and serum ALT, respectively. CO limited HS/R-induced increases in serum tumor necrosis factor-alpha and interleukin-6 levels as determined by ELISA (P < 0.05 for doses of 100-500ppm). Furthermore, inhaled CO limited HS/R induced oxidative stress as determined by hepatic oxidized glutathione: reduced glutathione levels and lipid peroxidation. In porcine HS/R, CO did not influence hemodynamics. However, CO limited HS/R-induced skeletal muscle and platelet mitochondrial injury as determined by respiratory control ratio (muscle) and ATP-linked respiration and mitochondrial reserve capacity (platelets). Conclusion These preclinical studies suggest that inhaled CO can be a protective therapy in HS/R; however, further clinical studies are warranted. C1 [Gomez, Hernando; Gordon, Lisa; Holder, Andre; Ogundele, Olufunmilayo; Rosengart, Matthew R.; Pinsky, Michael] Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA USA. [Gomez, Hernando; Rosengart, Matthew R.; Zuckerbraun, Brian S.] Univ Pittsburgh, Ctr Crit Care Nephrol, Pittsburgh, PA 15260 USA. [Kautza, Benjamin; Escobar, Daniel; Nassour, Ibrahim; Luciano, Jason; Botero, Ana Maria; Martinez, Silvia; Loughran, Patricia; Zuckerbraun, Brian S.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Shiva, Sruti] Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15261 USA. [Shiva, Sruti; Zuckerbraun, Brian S.] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA USA. [Zuckerbraun, Brian S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Zuckerbraun, BS (reprint author), Univ Pittsburgh, Ctr Crit Care Nephrol, Pittsburgh, PA 15260 USA. EM zuckerbraunbs@upmc.edu OI Nassour, Ibrahim/0000-0002-9845-1074 FU National Institutes of Health [R01GM082830, UM1 HL120877-01, 1K12HL109068-02]; Veterans Affairs Merit Award [1I01BX000566]; Department of Defense [DM102439]; Hemophilia Center of Western Pennsylvania; UPMC Military Medicine Center FX This work is supported by National Institutes of Health grants R01GM082830 (BSZ), UM1 HL120877-01 (BSZ), 1K12HL109068-02 (HG), Veterans Affairs Merit Award 1I01BX000566 (BSZ), Department of Defense DM102439 (BSZ), Hemophilia Center of Western Pennsylvania (SS) and UPMC Military Medicine Center (SS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 33 TC 0 Z9 0 U1 5 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 14 PY 2015 VL 10 IS 9 AR e0135032 DI 10.1371/journal.pone.0135032 PG 20 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CR8KS UT WOS:000361601100008 PM 26366865 ER PT J AU Lee, SH Hayano, K Zhu, AX Sahani, DV Yoshida, H AF Lee, Sang Ho Hayano, Koichi Zhu, Andrew X. Sahani, Dushyant V. Yoshida, Hiroyuki TI Water-Exchange-Modified Kinetic Parameters from Dynamic Contrast-Enhanced MRI as Prognostic Biomarkers of Survival in Advanced Hepatocellular Carcinoma Treated with Antiangiogenic Monotherapy SO PLOS ONE LA English DT Article ID TRACER KINETICS; BLOOD-VOLUME; IN-VIVO; CAPILLARY-PERMEABILITY; HEPATIC METASTASES; T-1-WEIGHTED MRI; SHUTTER-SPEED; DCE-MRI; PERFUSION; CANCER AB Background To find prognostic biomarkers in pretreatment dynamic contrast-enhanced MRI (DCE-MRI) water-exchange-modified (WX) kinetic parameters for advanced hepatocellular carcinoma (HCC) treated with antiangiogenic monotherapy. Methods Twenty patients with advanced HCC underwent DCE-MRI and were subsequently treated with sunitinib. Pretreatment DCE-MRI data on advanced HCC were analyzed using five different WX kinetic models: the Tofts-Kety (WX-TK), extended TK (WX-ETK), two compartment exchange, adiabatic approximation to tissue homogeneity (WX-AATH), and distributed parameter (WX-DP) models. The total hepatic blood flow, arterial flow fraction (gamma), arterial blood flow (BFA), portal blood flow, blood volume, mean transit time, permeability-surface area product, fractional interstitial volume (v(I)), extraction fraction, mean intracellular water molecule lifetime (tau(C)), and fractional intracellular volume (v(C)) were calculated. After receiver operating characteristic analysis with leave-one-out cross-validation, individual parameters for each model were assessed in terms of 1-year-survival (1YS) discrimination using Kaplan-Meier analysis, and association with overall survival (OS) using univariate Cox regression analysis with permutation testing. Results The WX-TK-model-derived. (P = 0.022) and v(I) (P = 0.010), and WX-ETK-model-derived tC (P = 0.023) and v(C) (P = 0.042) were statistically significant prognostic biomarkers for 1YS. Increase in the WX-DP-model-derived BFA (P = 0.025) and decrease in the WX-TK, WX-ETK, WX-AATH, and WX-DP-model-derived v(C) (P = 0.034, P = 0.038, P = 0.028, P = 0.041, respectively) were significantly associated with an increase in OS. Conclusions The WX-ETK-model-derived v(C) was an effective prognostic biomarker for advanced HCC treated with sunitinib. C1 [Lee, Sang Ho; Yoshida, Hiroyuki] Massachusetts Gen Hosp, Dept Radiol, Imaging Res 3D, Boston, MA 02114 USA. [Lee, Sang Ho; Yoshida, Hiroyuki] Harvard Univ, Sch Med, Boston, MA USA. [Hayano, Koichi; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA USA. [Zhu, Andrew X.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Yoshida, H (reprint author), Massachusetts Gen Hosp, Dept Radiol, Imaging Res 3D, Boston, MA 02114 USA. EM yoshida.hiro@mgh.harvard.edu RI Lee, Sang Ho/B-9149-2017 OI Lee, Sang Ho/0000-0002-4634-4904 FU National Institutes of Health [R21CA187877] FX Part of this work was supported by the National Institutes of Health grant (http://grants.nih.gov/grants/oer.htm) of R21CA187877 (PI: Yoshida). National Institutes of Health had a role in supporting, through the above grant, the development of the software that implemented kinetic models used for the analysis of the DCE-MRI data in this study. The majority of the study presented in manuscript was done under the "work made for hire" by the affiliated institution (MGH), which is, by nature, not an explicit funding dedicated to the study. Thus, there is no explicit funding other than what was stated. NR 55 TC 0 Z9 0 U1 1 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 14 PY 2015 VL 10 IS 9 AR e0136725 DI 10.1371/journal.pone.0136725 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CR8KS UT WOS:000361601100023 ER PT J AU Wang, H Shun, MC Dickson, AK Engelman, AN AF Wang, Hao Shun, Ming-Chieh Dickson, Amy K. Engelman, Alan N. TI Embryonic Lethality Due to Arrested Cardiac Development in Psip1/Hdgfrp2 Double-Deficient Mice SO PLOS ONE LA English DT Article ID GROWTH-FACTOR-BETA; GROWTH-FACTOR-BETA-1 KNOCKOUT MICE; INTEGRATION SITE SELECTION; FOCAL ADHESION KINASE; HIV-1 INTEGRASE; TRANSCRIPTIONAL COACTIVATOR; GENE-EXPRESSION; CHROMATIN BINDING; CELL-ADHESION; LEDGF/P75 AB Hepatoma-derived growth factor (HDGF) related protein 2 (HRP2) and lens epitheliumderived growth factor (LEDGF)/p75 are closely related members of the HRP2 protein family. LEDGF/p75 has been implicated in numerous human pathologies including cancer, autoimmunity, and infectious disease. Knockout of the Psip1 gene, which encodes for LEDGF/p75 and the shorter LEDGF/p52 isoform, was previously shown to cause perinatal lethality in mice. The function of HRP2 was by contrast largely unknown. To learn about the role of HRP2 in development, we knocked out the Hdgfrp2 gene, which encodes for HRP2, in both normal and Psip1 knockout mice. Hdgfrp2 knockout mice developed normally and were fertile. By contrast, the double deficient mice died at approximate embryonic day (E) 13.5. Histological examination revealed ventricular septal defect (VSD) associated with E14.5 double knockout embryos. To investigate the underlying molecular mechanism(s), RNA recovered from ventricular tissue was subjected to RNA-sequencing on the Illumina platform. Bioinformatic analysis revealed several genes and biological pathways that were significantly deregulated by the Psip1 knockout and/or Psip1/Hdgfrp2 double knockout. Among the dozen genes known to encode for LEDGF/p75 binding factors, only the expression of Nova1, which encodes an RNA splicing factor, was significantly deregulated by the knockouts. However the expression of other RNA splicing factors, including the LEDGF/p52-interacting protein ASF/SF2, was not significantly altered, indicating that deregulation of global RNA splicing was not a driving factor in the pathology of the VSD. Tumor growth factor (Tgf) beta-signaling, which plays a key role in cardiac morphogenesis during development, was the only pathway significantly deregulated by the double knockout as compared to control and Psip1 knockout samples. We accordingly speculate that deregulated Tgf-beta signaling was a contributing factor to the VSD and prenatal lethality of Psip1/Hdgfrp2 double-deficient mice. C1 [Engelman, Alan N.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Engelman, AN (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. EM alan_engelman@dfic.harvard.edu FU US National Institutes of Health [R37 AI039394] FX This work was supported by US National Institutes of Health grant R37 AI039394 to ANE. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 62 TC 6 Z9 6 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 14 PY 2015 VL 10 IS 9 AR e0137797 DI 10.1371/journal.pone.0137797 PG 20 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CR8KS UT WOS:000361601100140 PM 26367869 ER PT J AU Wang, XF Zhao, X Feng, C Weinstein, A Xia, R Wen, W Lv, QS Zuo, ST Tang, PJ Yang, X Chen, XJ Wang, HR Zang, SY Stollings, L Denning, TL Jiang, JJ Fan, J Zhang, GB Zhang, XG Zhu, YB Storkus, W Lu, BF AF Wang, Xuefeng Zhao, Xin Feng, Chao Weinstein, Aliyah Xia, Rui Wen, Wen Lv, Quansheng Zuo, Shuting Tang, Peijun Yang, Xi Chen, Xiaojuan Wang, Hongrui Zang, Shayang Stollings, Lindsay Denning, Timothy L. Jiang, Jingting Fan, Jie Zhang, Guangbo Zhang, Xueguang Zhu, Yibei Storkus, Walter Lu, Binfeng TI IL-36 gamma Transforms the Tumor Microenvironment and Promotes Type 1 Lymphocyte-Mediated Antitumor Immune Responses SO CANCER CELL LA English DT Article ID NF-KAPPA-B; T-CELLS; CANCER; EXPRESSION; MELANOMA; ANTIBODY; SKIN; TH1; IMMUNOGENICITY; ACTIVATION AB Cytokines play a pivotal role in regulating tumor immunogenicity and antitumor immunity. IL-36 gamma is important for the IL-23/IL-17-dominated inflammation and anti-BCG Th1 immune responses. However, the impact of IL-36 gamma on tumor immunity is unknown. Here we found that IL-36 gamma stimulated CD8(+) T cells, NK cells, and gamma delta T cells synergistically with TCR signaling and/or IL-12. Importantly, IL-36 gamma exerted profound antitumor effects in vivo and transformed the tumor microenvironment in favor of tumor eradication. Furthermore, IL-36 gamma strongly increased the efficacy of tumor vaccination. Moreover, IL-36 gamma expression inversely correlated with the progression of human melanoma and lung cancer. Our study establishes a role of IL-36 gamma in promoting antitumor immune responses and suggests its potential clinical translation into cancer immunotherapy. C1 [Wang, Xuefeng; Zhao, Xin; Weinstein, Aliyah; Xia, Rui; Zuo, Shuting; Yang, Xi; Chen, Xiaojuan; Zang, Shayang; Storkus, Walter; Lu, Binfeng] Univ Pittsburgh, Sch Med, Dept Immunol, Pittsburgh, PA 15261 USA. [Wang, Xuefeng] Soochow Univ, Sch Biol & Basic Med Sci, Dept Biochem & Mol Biol, Suzhou 215123, Peoples R China. [Wang, Xuefeng; Feng, Chao; Xia, Rui; Wen, Wen; Lv, Quansheng; Zang, Shayang; Zhang, Xueguang; Zhu, Yibei] Soochow Univ, Sch Biol & Basic Med Sci, Inst Med Biotechnol, Dept Immunol, Suzhou 215123, Peoples R China. [Lu, Binfeng] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15261 USA. [Jiang, Jingting] Soochow Univ, Affiliated Hosp 3, Dept Tumor Biotherapy, Changzhou 213003, Peoples R China. [Wang, Hongrui] Xiamen Univ, Sch Life Sci, Innovat Ctr Cell Biol, State Key Lab Cellular Stress Biol, Xiamen 361102, Fujian, Peoples R China. [Stollings, Lindsay] Univ Pittsburgh, Med Ctr, Dept Anesthesiol, Pittsburgh, PA 15213 USA. [Weinstein, Aliyah; Storkus, Walter] Univ Pittsburgh, Sch Med, Dept Dermatol, Pittsburgh, PA 15213 USA. [Zhao, Xin] Soochow Univ, Affiliated Hosp 1, Dept Gen Surg, Suzhou 215006, Peoples R China. [Yang, Xi] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China. [Tang, Peijun] Soochow Univ, Affiliated Hosp Infect Dis, Dept Pulm TB, Suzhou 215007, Peoples R China. [Zhang, Guangbo] Soochow Univ, Affiliated Hosp 1, Jiangsu Inst Clin Immunol, Suzhou 215006, Peoples R China. [Denning, Timothy L.] Georgia State Univ, Inst Biomed Sci, Ctr Inflammat Immun & Infect, Atlanta, GA 30303 USA. [Zuo, Shuting] Jilin Univ, Hosp 2, Dept Surg, Changchun 130041, Peoples R China. [Fan, Jie] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA 15213 USA. [Fan, Jie] Vet Affairs Pittsburgh Healthcare Syst, Res & Dev, Pittsburgh, PA 15240 USA. [Chen, Xiaojuan] Soochow Univ, Affiliated Hosp 1, Dept Gastroenterol, Suzhou 215006, Peoples R China. RP Lu, BF (reprint author), Univ Pittsburgh, Sch Med, Dept Immunol, 200 Lothrop St, Pittsburgh, PA 15261 USA. EM binfeng@pitt.edu FU NIH [R21CA167229, UL1 RR024153, UL1TR000005, 1P50 CA097190, T32 GM075770]; Roswell Park Cancer Institute/University of Pittsburgh Cancer Institute Ovarian Cancer Specialized Programs of Research Excellence [P50CA159981]; National Natural Science Foundation of China (NSFC) [31428005, 31320103918, 81273208]; 973 grant [2013CB530501] FX The project was mainly supported by the NIH through grants R21CA167229, UL1 RR024153, UL1TR000005, and 1P50 CA097190 (to B.L.); Roswell Park Cancer Institute/University of Pittsburgh Cancer Institute Ovarian Cancer Specialized Programs of Research Excellence grant P50CA159981 (to B.L.); National Natural Science Foundation of China (NSFC) grants 31428005 (to B.L. and J.J.), 31320103918 (to X.Z. and B.L.), and 81273208 (to Y.Z.); and 973 grant 2013CB530501 (to X.Z.). L.S. is supported by NIH grant T32 GM075770. R.X., S.Z., X.Y., and X.C. are supported by a scholarship from the NSFC. NR 38 TC 4 Z9 4 U1 1 U2 15 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 SEP 14 PY 2015 VL 28 IS 3 BP 296 EP 306 DI 10.1016/j.ccell.2015.07.014 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CR5YS UT WOS:000361420900008 PM 26321222 ER PT J AU White, JM Dunham, E Rowley, B Reisner, SL Mimiaga, MJ AF White, Jaclyn M. Dunham, Emilia Rowley, Blake Reisner, Sari L. Mimiaga, Matthew J. TI Sexually explicit racialised media targeting men who have sex with men online: a content analysis of high-risk behaviour depicted in online advertisements SO CULTURE HEALTH & SEXUALITY LA English DT Article DE advertisements; men who have sex with men; Black men; Internet; sexually explicit media ID ISLANDER GAY MEN; HIV RISK; BODY-IMAGE; CONDOM USE; PACIFIC ISLANDER; PORNOGRAPHY CONSUMPTION; PARTNER SELECTION; AFRICAN-AMERICAN; INTERNET; RACE AB Sexually explicit media may perpetuate racial and sexual norms among men who have sex with men. While men may be exposed to sexually explicit media in the online settings where they seek sex with other men, no studies to our knowledge have explored the relationship between the racial and sexual content of advertisements appearing in these spaces. In 2011, using a detailed codebook, 217 sexually explicit advertisements on a male sex-seeking website were coded for themes, actor characteristics and sexual acts depicted. Multivariable logistic regression models examined the association between skin colour, theme, sexual acts and condomless sex acts. Nearly half (45%) featured a 'thug' theme (a style emphasising Black masculinity/hip-hop culture), 21% featured a college theme and 44% featured condomless sex. Advertisements featuring only Black men, advertisements featuring Black men with men of other skin tones and advertisements depicting a thug theme were positively associated with depictions of condomless sex. Online sexually explicit advertisements featuring Black themes and actors more frequently depicted condomless sex than advertisements with White men alone. Future research should examine whether depictions of Black men engaging in condomless sex in online advertisements influence the sexual norms and cognitions of Black men who have sex with men and their partners. C1 [White, Jaclyn M.; Dunham, Emilia; Reisner, Sari L.; Mimiaga, Matthew J.] Fenway Hlth, Fenway Inst, Boston, MA 02215 USA. [White, Jaclyn M.] Yale Univ, Sch Publ Hlth, Dept Epidemiol, New Haven, CT USA. [Rowley, Blake] Natl Alliance State & Terr AIDS Directors, Washington, DC USA. [Reisner, Sari L.; Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP White, JM (reprint author), Fenway Hlth, Fenway Inst, Boston, MA 02215 USA. EM jwhite@fenwayhealth.org FU Fenway Institute, Fenway Health Boston; National Institute of Mental Health [T32MH020031, P30MH062294] FX This research was supported by The Fenway Institute, Fenway Health Boston. Jaclyn White is supported by Award Numbers T32MH020031 and P30MH062294 from the National Institute of Mental Health. NR 71 TC 1 Z9 1 U1 2 U2 11 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1369-1058 EI 1464-5351 J9 CULT HEALTH SEX JI Cult. Health Sex PD SEP 14 PY 2015 VL 17 IS 8 BP 1021 EP 1034 DI 10.1080/13691058.2015.1027738 PG 14 WC Family Studies; Social Sciences, Biomedical SC Family Studies; Biomedical Social Sciences GA CN4QV UT WOS:000358416200007 PM 25891135 ER PT J AU Akindana, A Ogunedo, C AF Akindana, Adeola Ogunedo, Chioma TI Managing type 2 diabetes in Black patients SO NURSE PRACTITIONER LA English DT Article AB Despite many novel treatments available for managing type 2 diabetes mellitus, Black patients continue to disproportionately suffer complications associated with poor glycemic control. This article describes a comprehensive approach to managing diabetes mellitus in these patients while addressing cultural nuances that may be barriers to positive outcomes. C1 [Akindana, Adeola] Doctors Community Hosp, Joslin Diabet Ctr, Lanham, MD USA. [Ogunedo, Chioma] Peace & Harmony Homecare LLC, Foxboro, MA USA. RP Akindana, A (reprint author), Doctors Community Hosp, Joslin Diabet Ctr, Lanham, MD 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 0361-1817 EI 1538-8662 J9 NURSE PRACT JI Nurse Pract. PD SEP 13 PY 2015 VL 40 IS 9 BP 20 EP 27 DI 10.1097/01.NPR.0000470354.00838.eb PG 8 WC Nursing SC Nursing GA DD0ZL UT WOS:000369650300004 PM 26259037 ER PT J AU Vaughn, LS Bragg, DC Sharma, N Camargos, S Cardoso, F Patel, RC AF Vaughn, Lauren S. Bragg, D. Cristopher Sharma, Nutan Camargos, Sarah Cardoso, Francisco Patel, Rekha C. TI Altered Activation of Protein Kinase PKR and Enhanced Apoptosis in Dystonia Cells Carrying a Mutation in PKR Activator Protein PACT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA-BINDING DOMAIN; 16 ACUTE ONSET; CELLULAR ACTIVATOR; MRI ABNORMALITIES; IN-VIVO; STRESS; INTERFERON; DYT16; PRKRA; IDENTIFICATION AB PACT is a stress-modulated activator of the interferon-induced double-stranded RNA-activated protein kinase (PKR). Stress-induced phosphorylation of PACT is essential for PACT's association with PKR leading to PKR activation. PKR activation leads to phosphorylation of translation initiation factor eIF2 alpha inhibition of protein synthesis and apoptosis. A recessively inherited form of early-onset dystonia DYT16 has been recently identified to arise due to a homozygous missense mutation P222L in PACT. To examine if the mutant P222L protein alters the stress-response pathway, we examined the ability of mutant P222L to interact with and activate PKR. Our results indicate that the substitution mutant P222L activates PKR more robustly and for longer duration albeit with slower kinetics in response to the endoplasmic reticulum stress. In addition, the affinity of PACT-PACT and PACT-PKR interactions is enhanced in dystonia patient lymphoblasts, thereby leading to intensified PKR activation and enhanced cellular death. P222L mutation also changes the affinity of PACT-TRBP interaction after cellular stress, thereby offering a mechanism for the delayed PKR activation in response to stress. Our results demonstrate the impact of a dystonia-causing substitution mutation on stress-induced cellular apoptosis. C1 [Vaughn, Lauren S.; Patel, Rekha C.] Univ S Carolina, Dept Biol Sci, Columbia, SC 29208 USA. [Bragg, D. Cristopher; Sharma, Nutan] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Camargos, Sarah; Cardoso, Francisco] Univ Fed Minas Gerais, Dept Internal Med, BR-31270901 Belo Horizonte, MG, Brazil. RP Patel, RC (reprint author), Univ S Carolina, Dept Biol Sci, 700 Sumter St, Columbia, SC 29208 USA. EM patelr@biol.sc.edu RI Patel, Rekha/M-7123-2015 OI Patel, Rekha/0000-0001-9434-4880 FU Dystonia Medical Research Foundation; National Institutes of Health (NINDS) [P50NS037409] FX This work was supported in part by a Dystonia Medical Research Foundation grant (to R. P.). The work was also supported by National Institutes of Health Grant P50NS037409 (NINDS; to N. S.). The authors declare that they have no conflicts of interest with the contents of this article. NR 50 TC 4 Z9 4 U1 0 U2 2 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 SEP 11 PY 2015 VL 290 IS 37 BP 22543 EP 22557 DI 10.1074/jbc.M115.669408 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CR2PB UT WOS:000361171500021 PM 26231208 ER PT J AU Levy, DE Adamkiewicz, G Rigotti, NA Fang, SC Winickoff, JP AF Levy, Douglas E. Adamkiewicz, Gary Rigotti, Nancy A. Fang, Shona C. Winickoff, Jonathan P. TI Changes in Tobacco Smoke Exposure following the Institution of a Smoke-Free Policy in the Boston Housing Authority SO PLOS ONE LA English DT Article ID SECONDHAND SMOKE; NICOTINE; COTININE; US AB Introduction To protect residents from tobacco smoke exposure (TSE), the Boston Housing Authority (BHA) prohibited smoking in BHA-owned apartments beginning in 2012. Our goal was to determine if the smoke-free policy reduced TSE for non-smoking BHA residents. Methods We compared TSE before the smoke-free policy (2012) and one year later among BHA residents as well as residents of the neighboring Cambridge Housing Authority (CHA) where no such policy was in place. Participants were a convenience sample of adult non-smoking BHA and CHA residents cohabitating with only non-smokers. Main outcomes were 7-day airborne nicotine in participants' apartments; residents' saliva cotinine; and residents' self-reported TSE. Results We enrolled 287 confirmed non-smokers (192 BHA, 95 CHA). Seventy-nine percent (229) were assessed at follow-up. At baseline, apartment and resident TSE were high in both housing authorities (detectable airborne nicotine: 46% BHA, 48% CHA; detectable saliva cotinine: 49% BHA, 70% CHA). At follow-up there were significant but similar declines in nicotine in both sites (detectable: -33% BHA, -39% CHA, p = 0.40). Detectable cotinine rose among BHA residents while declining among CHA participants (+17% BHA vs. -13% CHA, p = 0.002). Resident self-reported TSE within and outside of the housing environment decreased similarly for both BHA and CHA residents. Conclusions Apartment air nicotine decreased after the introduction of the smoke-free policy, though the decline may not have resulted from the policy. The BHA policy did not result in reduced individual-level TSE. Unmeasured sources of non-residential TSE may have contributed to BHA residents' cotinine levels. C1 [Levy, Douglas E.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Levy, Douglas E.; Rigotti, Nancy A.; Winickoff, Jonathan P.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Levy, Douglas E.; Rigotti, Nancy A.; Winickoff, Jonathan P.] Harvard Univ, Sch Med, Boston, MA USA. [Adamkiewicz, Gary; Fang, Shona C.] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Fang, Shona C.] New England Res Inst, Watertown, MA 02172 USA. [Winickoff, Jonathan P.] Massachusetts Gen Hosp Children, Div Gen Pediat, Boston, MA USA. RP Levy, DE (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. EM dlevy3@mgh.harvard.edu FU National Institutes of Health/National Heart, Lung, and Blood Institute [R01-HL112212]; Flight Attendants Medical Research Institute FX Funding: Support was provided by the National Institutes of Health/National Heart, Lung, and Blood Institute R01-HL112212 (www.nhlbi.nih.gov) to DEL, GA, NAR, SCF, and JPW; and by the Flight Attendants Medical Research Institute (www.famri.org) to DEL. Neither funder had any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 TC 1 Z9 1 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 11 PY 2015 VL 10 IS 9 AR e0137740 DI 10.1371/journal.pone.0137740 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CR0WB UT WOS:000361043100078 PM 26360258 ER PT J AU Biddinger, PD Hooper, DC Shenoy, ES Bajwa, EK Robbins, GK Branda, JA AF Biddinger, Paul D. Hooper, David C. Shenoy, Erica S. Bajwa, Ednan K. Robbins, Gregory K. Branda, John A. TI Case 28-2015: A 32-Year-Old Man with Fever, Headache, and Myalgias after Traveling from Liberia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID EBOLA-VIRUS DISEASE; MALARIA; ILLNESS C1 [Biddinger, Paul D.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Hooper, David C.; Shenoy, Erica S.; Robbins, Gregory K.] Massachusetts Gen Hosp, Dept Infect Dis, Boston, MA 02114 USA. [Bajwa, Ednan K.] Massachusetts Gen Hosp, Dept Pulm & Crit Care, Boston, MA 02114 USA. [Branda, John A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hooper, David C.; Shenoy, Erica S.] Massachusetts Gen Hosp, Infect Control Unit, Boston, MA 02114 USA. [Biddinger, Paul D.] Harvard Univ, Dept Emergency Med, Sch Med, Boston, MA USA. [Hooper, David C.; Shenoy, Erica S.; Bajwa, Ednan K.; Robbins, Gregory K.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Branda, John A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Biddinger, PD (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. NR 13 TC 1 Z9 1 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 10 PY 2015 VL 373 IS 11 BP 1060 EP 1067 DI 10.1056/NEJMcpc1503828 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA CQ9TV UT WOS:000360959000013 PM 26352818 ER PT J AU Wright, AA Cronin, A Milne, DE Bookman, MA Burger, RA Cohn, DE Cristea, MC Griggs, JJ Keating, NL Levenback, CF Mantia-Smaldone, G Matulonis, UA Meyer, LA Niland, JC Weeks, JC O'Malley, DM AF Wright, Alexi A. Cronin, Angel Milne, Dana E. Bookman, Michael A. Burger, Robert A. Cohn, David E. Cristea, Mihaela C. Griggs, Jennifer J. Keating, Nancy L. Levenback, Charles F. Mantia-Smaldone, Gina Matulonis, Ursula A. Meyer, Larissa A. Niland, Joyce C. Weeks, Jane C. O'Malley, David M. TI Use and Effectiveness of Intraperitoneal Chemotherapy for Treatment of Ovarian Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ADVANCED EPITHELIAL OVARIAN; GYNECOLOGIC-ONCOLOGY-GROUP; PRIMARY PERITONEAL CANCER; FALLOPIAN-TUBE; INTRAVENOUS PACLITAXEL; CISPLATIN; SURVIVAL; WOMEN; RECURRENCE; PATTERNS AB Purpose A 2006 randomized trial demonstrated a 16-month survival benefit with intraperitoneal and intravenous (IP/IV) chemotherapy administered to patients who had ovarian cancer, compared with IV chemotherapy alone, but more treatment-related toxicities. The objective of this study was to examine the use and effectiveness of IP/IV chemotherapy in clinical practice. Patients and Methods Prospective cohort study of 823 women with stage III, optimally cytoreduced ovarian cancer diagnosed at six National Comprehensive Cancer Network institutions. We examined IP/IV chemotherapy use in all patients diagnosed between 2003 and 2012 (N = 823), and overall survival and treatment-related toxicities with Cox regression and logistic regression, respectively, in a propensity score-matched sample (n = 402) of patients diagnosed from 2006 to 2012, excluding trial participants, to minimize selection bias. Results Use of IP/IV chemotherapy increased from 0% to 33% between 2003 and 2006, increased to 50% from 2007 to 2008, and plateaued thereafter. Between 2006 and 2012, adoption of IP/IV chemotherapy varied by institution from 4% to 67% (P < .001) and 43% of patients received modified IP/IV regimens at treatment initiation. In the propensity score-matched sample, IP/IV chemotherapy was associated with significantly improved overall survival (3-year overall survival, 81% v 71%; hazard ratio, 0.68; 95% CI, 0.47 to 0.99), compared with IV chemotherapy, but also more frequent alterations in chemotherapy delivery route (adjusted rates discontinuation or change, 20.4% v 10.0%; adjusted odds ratio, 2.83; 95% CI, 1.47 to 5.47). Conclusion Although the use of IP/IV chemotherapy increased significantly at National Comprehensive Cancer Network centers between 2003 and 2012, fewer than 50% of eligible patients received it. Increasing IP/IV chemotherapy use in clinical practice may be an important and underused strategy to improve ovarian cancer outcomes. (C) 2015 by American Society of Clinical Oncology C1 [Wright, Alexi A.; Cronin, Angel; Milne, Dana E.; Keating, Nancy L.; Matulonis, Ursula A.; Weeks, Jane C.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Bookman, Michael A.] Univ Arizona, Ctr Canc, Tucson, AZ USA. [Burger, Robert A.] Univ Penn, Philadelphia, PA 19104 USA. [Mantia-Smaldone, Gina] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Cohn, David E.; O'Malley, David M.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Cristea, Mihaela C.; Niland, Joyce C.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Griggs, Jennifer J.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Levenback, Charles F.; Meyer, Larissa A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Wright, AA (reprint author), Dana Farber Canc Inst, Dana 1133,450 Brookline Ave, Boston, MA 02215 USA. EM alexi_wright@dfci.harvard.edu RI OMalley, David/E-3789-2011 FU National Cancer Institute [K07 CA166210] FX Supported by the National Cancer Institute Grant No. K07 CA166210 (to A.A.W.). NR 35 TC 21 Z9 22 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 SEP 10 PY 2015 VL 33 IS 26 BP 2841 EP + DI 10.1200/JCO.2015.61.4776 PG 11 WC Oncology SC Oncology GA CX9ID UT WOS:000366017800005 PM 26240233 ER PT J AU Palumbo, A Avet-Loiseau, H Oliva, S Lokhorst, HM Goldschmidt, H Rosinol, L Richardson, P Caltagirone, S Lahuerta, JJ Facon, T Bringhen, S Gay, F Attal, M Passera, R Spencer, A Offidani, M Kumar, S Musto, P Lonial, S Petrucci, MT Orlowski, RZ Zamagni, E Morgan, G Dimopoulos, MA Durie, BGM Anderson, KC Sonneveld, P Miguel, JS Cavo, M Rajkumar, SV Moreau, P AF Palumbo, Antonio Avet-Loiseau, Herve Oliva, Stefania Lokhorst, Henk M. Goldschmidt, Hartmut Rosinol, Laura Richardson, Paul Caltagirone, Simona Jose Lahuerta, Juan Facon, Thierry Bringhen, Sara Gay, Francesca Attal, Michel Passera, Roberto Spencer, Andrew Offidani, Massimo Kumar, Shaji Musto, Pellegrino Lonial, Sagar Petrucci, Maria T. Orlowski, Robert Z. Zamagni, Elena Morgan, Gareth Dimopoulos, Meletios A. Durie, Brian G. M. Anderson, Kenneth C. Sonneveld, Pieter San Miguel, Jesus Cavo, Michele Rajkumar, S. Vincent Moreau, Philippe TI Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID STEM-CELL TRANSPLANTATION; LACTATE-DEHYDROGENASE; BORTEZOMIB INDUCTION; PLUS DEXAMETHASONE; RANDOMIZED PHASE-3; HIGH-RISK; MAINTENANCE; THALIDOMIDE; THERAPY; TRIAL AB Purpose The clinical outcome of multiple myeloma (MM) is heterogeneous. A simple and reliable tool is needed to stratify patients with MM. We combined the International Staging System (ISS) with chromosomal abnormalities (CA) detected by interphase fluorescent in situ hybridization after CD138 plasma cell purification and serum lactate dehydrogenase (LDH) to evaluate their prognostic value in newly diagnosed MM (NDMM). Patients and Methods Clinical and laboratory data from 4,445 patients with NDMM enrolled onto 11 international trials were pooled together. The K-adaptive partitioning algorithm was used to define the most appropriate subgroups with homogeneous survival. Results ISS, CA, and LDH data were simultaneously available in 3,060 of 4,445 patients. We defined the following three groups: revised ISS (R-ISS) I (n = 871), including ISS stage I (serum beta(2)-microglobulin level < 3.5 mg/L and serum albumin level >= 3.5 g/dL), no high-risk CA [del(17p) and/or t(4; 14) and/or t(14; 16)], and normal LDH level (less than the upper limit of normal range); R-ISS III (n = 295), including ISS stage III (serum beta(2)-microglobulin level > 5.5 mg/L) and high-risk CA or high LDH level; and R-ISS II (n = 1,894), including all the other possible combinations. At a median follow-up of 46 months, the 5-year OS rate was 82% in the R-ISS I, 62% in the R-ISS II, and 40% in the R-ISS III groups; the 5-year PFS rates were 55%, 36%, and 24%, respectively. Conclusion The R-ISS is a simple and powerful prognostic staging system, and we recommend its use in future clinical studies to stratify patients with NDMM effectively with respect to the relative risk to their survival. (C) 2015 by American Society of Clinical Oncology C1 [Palumbo, Antonio; Oliva, Stefania; Caltagirone, Simona; Bringhen, Sara; Gay, Francesca] Univ Turin, Azienda Osped Univ Citta Salute Salute & Sci Tori, Turin, Italy. [Passera, Roberto] Univ Turin, Turin, Italy. [Offidani, Massimo] AUO Osped Riuniti Ancona, Clin Ematol, Ancona, Italy. [Musto, Pellegrino] IRCCS, Referral Canc Ctr Basilicata, Rionero In Vulture, Italy. [Petrucci, Maria T.] Univ Roma La Sapienza, I-00185 Rome, Italy. [Zamagni, Elena; Cavo, Michele] Univ Bologna, Ist Ematol Seragnoli, Bologna, Italy. [Avet-Loiseau, Herve; Attal, Michel] Inst Univ Canc Toulouse Oncopole, Inst Claudius Regaud, Toulouse, France. [Facon, Thierry] Ctr Hosp Reg & Univ Lille, Hop Claude Huriez, Serv Malad Sang, F-59037 Lille, France. [Moreau, Philippe] Univ Hosp Hotel Dieu, Nantes, France. [Lokhorst, Henk M.] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. [Sonneveld, Pieter] Erasmus MC, Rotterdam, Netherlands. [Goldschmidt, Hartmut] Univ Hosp, Heidelberg, Germany. [Goldschmidt, Hartmut] Natl Ctr Tumor Dis Heidelberg, Heidelberg, Germany. [Rosinol, Laura] Hosp Clin Barcelona, Inst Clin Invest Biomed Ausgust Pi & Sunyer, Barcelona, Spain. [Jose Lahuerta, Juan] Hosp Univ 12 Octubre, Madrid, Spain. [San Miguel, Jesus] Univ Navarra Clin, Ctr Invest Med Aplicadas, IDISNA, Pamplona, Spain. [Richardson, Paul; Anderson, Kenneth C.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Kumar, Shaji; Rajkumar, S. Vincent] Mayo Clin, Rochester, MN USA. [Lonial, Sagar] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Orlowski, Robert Z.] Univ Texas MD Anderson Comprehens Canc Ctr, Houston, TX USA. [Morgan, Gareth] Univ Arkansas Med Sci, Myeloma Inst Res Therapy, Little Rock, AR 72205 USA. [Durie, Brian G. M.] Cedars Sinai Comprehens Canc Ctr, Los Angeles, CA USA. [Spencer, Andrew] Alfred Hlth Hosp, Melbourne, Vic, Australia. [Dimopoulos, Meletios A.] Univ Athens, Sch Med, Athens 11528, Greece. RP Palumbo, A (reprint author), Azienda Osped Univ Citta Salute & Sci Torino, Dipartimento Oncol & Ematol, Via Genova 3, I-10126 Turin, Italy. EM appalumbo@yahoo.com RI FACON, THIERRY/M-9736-2014; richard, chrystelle/K-8595-2015; OI FACON, THIERRY/0000-0001-7705-8460; CAVO, MICHELE/0000-0003-4514-3227; Musto, Pellegrino/0000-0003-3277-6594 FU NCI NIH HHS [P30 CA016672, P50 CA142509, U10 CA032102, U10 CA180888] NR 29 TC 73 Z9 82 U1 1 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 10 PY 2015 VL 33 IS 26 BP 2863 EP + DI 10.1200/JCO.2015.61.2267 PG 16 WC Oncology SC Oncology GA CX9ID UT WOS:000366017800008 PM 26240224 ER PT J AU Madenci, AL Fisher, S Diller, LR Goldsby, RE Leisenring, WM Oeffinger, KC Robison, LL Sklar, CA Stovall, M Weathers, RE Armstrong, GT Yasui, Y Weldon, CB AF Madenci, Arin L. Fisher, Stacey Diller, Lisa R. Goldsby, Robert E. Leisenring, Wendy M. Oeffinger, Kevin C. Robison, Leslie L. Sklar, Charles A. Stovall, Marilyn Weathers, Rita E. Armstrong, Gregory T. Yasui, Yutaka Weldon, Christopher B. TI Intestinal Obstruction in Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SMALL-BOWEL OBSTRUCTION; PREOPERATIVE CONSENT; RADIATION-THERAPY; WILMS-TUMOR; CHILDREN; COMPLICATIONS; APPENDECTOMY; EXPERIENCE; ADHESIONS; MODELS AB Purpose For adult survivors of childhood cancer, knowledge about the long-term risk of intestinal obstruction from surgery, chemotherapy, and radiotherapy is limited. Methods Intestinal obstruction requiring surgery (IOS) occurring 5 or more years after cancer diagnosis was evaluated in 12,316 5-year survivors in the Childhood Cancer Survivor Study (2,002 with and 10,314 without abdominopelvic tumors) and 4,023 sibling participants. Cumulative incidence of IOS was calculated with second malignant neoplasm, late recurrence, and death as competing risks. Using piecewise exponential models, we assessed the associations of clinical and demographic factors with rate of IOS. Results Late IOS was reported by 165 survivors (median age at IOS, 19 years; range, 5 to 50 years; median time from diagnosis to IOS, 13 years) and 14 siblings. The cumulative incidence of late IOS at 35 years was 5.8% (95% CI, 4.4% to 7.3%) among survivors with abdominopelvic tumors, 1.0% (95% CI, 0.7% to 1.4%) among those without abdominopelvic tumors, and 0.3% (95% CI, 0.1% to 0.5%) among siblings. Among survivors, abdominopelvic tumor (adjusted rate ratio [ARR], 3.6; 95% CI, 1.9 to 6.8; P < .001) and abdominal/pelvic radiotherapy within 5 years of cancer diagnosis (ARR, 2.4; 95% CI, 1.6 to 3.7; P < .001) increased the rate of late IOS, adjusting for diagnosis year; sex; race/ethnicity; age at diagnosis; age during follow-up (as natural cubic spline); cancer type; and chemotherapy, radiotherapy, and surgery within 5 years of cancer diagnosis. Developing late IOS increased subsequent mortality among survivors (ARR, 1.8; 95% CI, 1.1 to 2.9; P = .016), adjusting for the same factors. Conclusion The long-term risk of IOS and its association with subsequent mortality underscore the need to promote awareness of this complication among patients and providers. (C) 2015 by American Society of Clinical Oncology C1 [Madenci, Arin L.; Weldon, Christopher B.] Boston Childrens Hosp, Boston, MA USA. [Madenci, Arin L.; Diller, Lisa R.; Weldon, Christopher B.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Madenci, Arin L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Diller, Lisa R.; Weldon, Christopher B.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fisher, Stacey; Yasui, Yutaka] Univ Alberta, Edmonton, AB, Canada. [Goldsby, Robert E.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Leisenring, Wendy M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Oeffinger, Kevin C.; Sklar, Charles A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Robison, Leslie L.; Armstrong, Gregory T.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Stovall, Marilyn; Weathers, Rita E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Weldon, CB (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Surg, 300 Longwood Ave,Fegan 3, Boston, MA 02114 USA. EM christopher.weldon@childrens.harvard.edu FU National Cancer Institute [CA55727]; Cancer Center Support (Centers of Research Excellence) [CA21765]; American Lebanese Syrian Associated Charities FX Supported by National Cancer Institute Grant No. CA55727 and Cancer Center Support (Centers of Research Excellence) Grant No. CA21765 to St Jude Children's Research Hospital, as well as the American Lebanese Syrian Associated Charities. NR 35 TC 3 Z9 3 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 SEP 10 PY 2015 VL 33 IS 26 BP 2893 EP + DI 10.1200/JCO.2015.61.5070 PG 10 WC Oncology SC Oncology GA CX9ID UT WOS:000366017800012 PM 26261256 ER PT J AU Meyer, LA Bohlke, K Powell, MA Fader, AN Franklin, GE Lee, LJ Matei, D Coallier, L Wright, AA AF Meyer, Larissa A. Bohlke, Kari Powell, Matthew A. Fader, Amanda N. Franklin, Gregg E. Lee, Larissa J. Matei, Daniela Coallier, Lourie Wright, Alexi A. TI Postoperative Radiation Therapy for Endometrial Cancer: American Society of Clinical Oncology Clinical Practice Guideline Endorsement of the American Society for Radiation Oncology Evidence-Based Guideline SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PHASE-III TRIAL; INTERMEDIATE-RISK; RANDOMIZED-TRIAL; ADJUVANT CHEMOTHERAPY; PELVIC RADIOTHERAPY; PORTEC-1 TRIAL; CARCINOMA; BRACHYTHERAPY; STATISTICS; OUTCOMES AB Purpose To provide guidance on the role of adjuvant radiation therapy in the treatment of endometrial cancer. Methods "The Role of Postoperative Radiation Therapy for Endometrial Cancer: An ASTRO Evidence-Based Guideline" by Klopp et al, published in 2014 in Practical Radiation Oncology, was reviewed for developmental rigor by methodologists. The American Society for Radiation Oncology (ASTRO) guideline content and recommendations were further reviewed by the American Society of Clinical Oncology (ASCO) Endorsement Panel. Results The ASCO Endorsement Panel determined that the recommendations from the ASTRO guideline are clear, thorough, and based on the most relevant scientific evidence. ASCO endorsed the ASTRO guideline with several qualifying statements. Recommendations Surveillance without adjuvant radiation therapy is a reasonable option for women without residual disease in the hysterectomy specimen and for women with grade 1 or 2 cancer and < 50% myometrial invasion, especially when no other high-risk features are present. For women with grade 1 or 2 cancer and >= 50% myometrial invasion or grade 3 cancer and < 50% myometrial invasion, vaginal brachytherapy is as effective as pelvic radiation therapy at preventing vaginal recurrence and is preferred. Patients with grade 3 cancer and >= 50% myometrial invasion or cervical stroma invasion may benefit from pelvic radiation to prevent pelvic recurrence. For women with high-risk early-stage disease and advanced disease, the ASCO Endorsement Panel added qualifying statements to the ASTRO recommendations to provide stronger statements in favor of chemotherapy (with or without radiation therapy). (C) 2015 by American Society of Clinical Oncology C1 [Meyer, Larissa A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Bohlke, Kari] Amer Soc Clin Oncol, Alexandria, VA 22314 USA. [Powell, Matthew A.] Washington Univ, Sch Med, St Louis, MO USA. [Fader, Amanda N.] Johns Hopkins Univ Hosp, Kelly Gynecol Oncol Serv, Baltimore, MD 21287 USA. [Franklin, Gregg E.] New Mexico Canc Ctr, Albuquerque, NM USA. [Lee, Larissa J.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Wright, Alexi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Matei, Daniela] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. RP Meyer, LA (reprint author), Amer Soc Clin Oncol, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA. EM guidelines@asco.org FU NCI NIH HHS [P30 CA016672] NR 19 TC 12 Z9 12 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 SEP 10 PY 2015 VL 33 IS 26 BP 2908 EP + DI 10.1200/JCO.2015.62.5459 PG 8 WC Oncology SC Oncology GA CX9ID UT WOS:000366017800014 PM 26150442 ER PT J AU Stewart, AK Jacobus, S Fonseca, R Weiss, M Callander, NS Chanan-Khan, AA Rajkumar, SV AF Stewart, A. Keith Jacobus, Susanna Fonseca, Rafael Weiss, Matthias Callander, Natalie S. Chanan-Khan, Asher A. Rajkumar, S. Vincent TI Melphalan, prednisone, and thalidomide vs melphalan, prednisone, and lenalidomide (ECOG E1A06) in untreated multiple myeloma SO BLOOD LA English DT Review ID TRANSPLANT-INELIGIBLE PATIENTS; BORTEZOMIB PLUS MELPHALAN; CLINICAL-TRIALS; INITIAL TREATMENT; ORAL MELPHALAN; DEXAMETHASONE; METAANALYSIS; MULTICENTER; MAINTENANCE; SURVIVAL AB This phase 3 trial (Eastern Cooperative Oncology Group [ECOG] E1A06) compared melphalan, prednisone, and thalidomide (MPT-T) with melphalan, prednisone, and lenalidomide (mPR-R) in patients with untreated multiple myeloma (MM). A noninferiority design was used, and inferiority was defined as a progression-free survival (PFS) hazard ratio (HR) of MPT-T/mPR-R <= 0.82. A total of 306 patients enrolled, with a median age of 75.7 years. Median follow-up was 40.7 months. Median time on therapy was 12.1 months and 23.1 months for the 46.6% of treated patients who received maintenance, with no differences by arm. Median PFS was 21 months on MPT-T and 18.7 months on mPR-R (HR, 0.84; 95% confidence interval, 0.64-1.09). Overall survival was 52.6 months (MPT-T) vs 47.7 months (mPR-R) (P =.476). Per-protocol response rates were 63.6% (MPT-T) and 59.9% (mPR-R) (P =.557). Grade >= 3 nonhematologic toxicity was 59.5% for MPT-T vs 40.0% for mPR-R (P =.001). Second malignancies were observed in 18 MPT-T patients vs 14 mPR-R patients. Quality-of-life analysis favored mPR-R by induction end (P =.007). Use of MPT-T or mPR-R in elderly patients with untreated MM demonstrates no statistical or clinically relevant differences in response rates, PFS, and OS; however, quality of life at end of induction was improved and lower toxicity reported with mPR-R. C1 [Stewart, A. Keith; Fonseca, Rafael] Mayo Clin Arizona, Div Hematol, Scottsdale, AZ 85259 USA. [Jacobus, Susanna] Dana Farber Canc Inst, Boston, MA 02115 USA. [Weiss, Matthias] Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA. [Callander, Natalie S.] Univ Wisconsin, Madison, WI USA. [Chanan-Khan, Asher A.] Mayo Clin, Div Hematol, Jacksonville, FL 32224 USA. [Rajkumar, S. Vincent] Mayo Clin, Div Hematol, Rochester, MN USA. RP Stewart, AK (reprint author), Mayo Clin Arizona, Div Hematol Oncol, Room 1-006,Collaborat Res Bldg,13400 E Shea Blvd, Scottsdale, AZ 85259 USA. EM stewart.keith@mayo.edu FU Public Health Service Grants [CA180820, CA180794, CA180790, CA189956, CA180799, CA31946]; National Cancer Institute, National Institutes of Health and the Department of Health and Human Services FX This study was supported in part by Public Health Service Grants CA180820, CA180794, CA180790, CA189956, CA180799, and CA31946 and by the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. NR 29 TC 10 Z9 10 U1 2 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD SEP 10 PY 2015 VL 126 IS 11 BP 1294 EP 1301 DI 10.1182/blood-2014-12-613927 PG 8 WC Hematology SC Hematology GA CU4EK UT WOS:000363479500011 PM 26157076 ER PT J AU Gerrits, AJ Leven, EA Frelinger, AL Brigstocke, SL Berny-Lang, MA Mitchell, WB Revel-Vilk, S Tamary, H Carmichael, SL Barnard, MR Michelson, AD Bussel, JB AF Gerrits, Anja J. Leven, Emily A. Frelinger, Andrew L., III Brigstocke, Sophie L. Berny-Lang, Michelle A. Mitchell, W. Beau Revel-Vilk, Shoshana Tamary, Hannah Carmichael, Sabrina L. Barnard, Marc R. Michelson, Alan D. Bussel, James B. TI Effects of eltrombopag on platelet count and platelet activation in Wiskott-Aldrich syndrome/X-linked thrombocytopenia SO BLOOD LA English DT Article ID CHRONIC IMMUNE THROMBOCYTOPENIA; SYNDROME PROTEIN; WASP GENE; LONG-TERM; MUTATIONS; CHILDREN; CLOPIDOGREL; INHIBITION; PERSISTENT; PRASUGREL AB Because Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT) patients have microthrombocytopenia, hemorrhage is a major problem. We asked whether eltrombopag, a thrombopoietic agent, would increase platelet counts, improve platelet activation, and/or reduce bleeding in WAS/XLT patients. In 9 WAS/XLT patients and 8 age-matched healthy controls, platelet activation was assessed by whole blood flow cytometry. Agonist-induced platelet surface activated glycoprotein (GP) IIb-IIIa and P-selectin in WAS/XLT patients were proportional to platelet size and therefore decreased compared with controls. In contrast, annexin V binding showed no differences between WAS/XLT and controls. Eltrombopag treatment resulted in an increased platelet count in 5 out of 8 patients. Among responders to eltrombopag, immature platelet fraction in 3WAS/XLT patients was significantly less increased compared with 7 pediatric chronic immune thrombocytopenia (ITP) patients. Platelet activation did not improve in 3 WAS/XLT patients whose platelet count improved on eltrombopag. In conclusion: (1) the reduced platelet activation observed in WAS/XLT is primarily due to the microthrombocytopenia; and (2) although the eltrombopag-induced increase in platelet production in WAS/XLT is less than in ITP, eltrombopag has beneficial effects on platelet count but not platelet activation in the majority of WAS/XLT patients. C1 [Gerrits, Anja J.; Frelinger, Andrew L., III; Berny-Lang, Michelle A.; Carmichael, Sabrina L.; Barnard, Marc R.; Michelson, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Boston Childrens Hosp, Ctr Platelet Res Studies,Div Hematol Oncol, Boston, MA 02115 USA. [Leven, Emily A.; Brigstocke, Sophie L.; Mitchell, W. Beau; Bussel, James B.] New York Presbyterian Hosp, Weill Cornell Med Coll, Div Pediat Hematol Oncol, New York, NY USA. [Mitchell, W. Beau] New York Blood Ctr, Platelet Biol Lab, New York, NY 10021 USA. [Revel-Vilk, Shoshana] Hadassah Hebrew Univ Hosp, Dept Pediat Hematol Oncol, Jerusalem, Israel. [Tamary, Hannah] Schneider Childrens Med Ctr Israel, Pediat Hematol Oncol, Petah Tiqwa, Israel. RP Michelson, AD (reprint author), Boston Childrens Hosp, Div Hematol Oncol, Ctr Platelet Res Studies, 300 Longwood Ave, Boston, MA 08213 USA. EM alan.michelson@childrens.harvard.edu; jbussel@med.cornell.edu FU Clinical and Translational Science Center at Weill Cornell Medical College [UL1TR00457]; GlaxoSmithKline; Children's Cancer and Blood Foundation FX This study was partly supported by a grant from the Clinical and Translational Science Center at Weill Cornell Medical College (#UL1TR00457); an unrestricted grant from GlaxoSmithKline; Sysmex for providing the XE-2100 instrument; and by the Children's Cancer and Blood Foundation. NR 47 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD SEP 10 PY 2015 VL 126 IS 11 BP 1367 EP 1378 DI 10.1182/blood-2014-09-602573 PG 12 WC Hematology SC Hematology GA CU4EK UT WOS:000363479500018 PM 26224646 ER PT J AU Sanchez-Guerrero, S Castillo, JJ AF Sanchez-Guerrero, Sergio Castillo, Jorge J. TI Bing-Neel syndrome: a rare complication of Waldenstrom macroglobulinemia SO BLOOD LA English DT Editorial Material C1 [Castillo, Jorge J.] Dana Farber Canc Inst, Boston, MA 02215 USA. OI Castillo, Jorge/0000-0001-9490-7532 NR 0 TC 2 Z9 2 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 SEP 10 PY 2015 VL 126 IS 11 BP 1390 EP 1390 DI 10.1182/blood-2015-05-640219 PG 1 WC Hematology SC Hematology GA CU4EK UT WOS:000363479500020 PM 26605390 ER PT J AU Kleffel, S Posch, C Barthel, SR Mueller, H Schlapbach, C Guenova, E Elco, CP Lee, N Juneja, VR Zhan, Q Lian, CG Thomi, R Hoetzenecker, W Cozzio, A Dummer, R Mihm, MC Flaherty, KT Frank, MH Murphy, GF Sharpe, AH Kupper, TS Schatton, T AF Kleffel, Sonja Posch, Christian Barthel, Steven R. Mueller, Hansgeorg Schlapbach, Christoph Guenova, Emmanuella Elco, Christopher P. Lee, Nayoung Juneja, Vikram R. Zhan, Qian Lian, Christine G. Thomi, Rahel Hoetzenecker, Wolfram Cozzio, Antonio Dummer, Reinhard Mihm, Martin C., Jr. Flaherty, Keith T. Frank, Markus H. Murphy, George F. Sharpe, Arlene H. Kupper, Thomas S. Schatton, Tobias TI Melanoma Cell-Intrinsic PD-1 Receptor Functions Promote Tumor Growth SO CELL LA English DT Article ID CANCER-IMMUNOTHERAPY; INITIATING CELLS; BLOCKADE; ACTIVATION; EXPRESSION; NIVOLUMAB; RESPONSES; ANTI-PD-1; PATHWAYS; ANTIBODY AB Therapeutic antibodies targeting programmed cell death 1 (PD-1) activate tumor-specific immunity and have shown remarkable efficacy in the treatment of melanoma. Yet, little is known about tumor cell-intrinsic PD-1 pathway effects. Here, we show that murine and human melanomas contain PD-1-expressing cancer subpopulations and demonstrate that melanoma cell-intrinsic PD-1 promotes tumorigenesis, even in mice lacking adaptive immunity. PD-1 inhibition on melanoma cells by RNAi, blocking antibodies, or mutagenesis of melanoma-PD-1 signaling motifs suppresses tumor growth in immunocompetent, immunocompromised, and PD-1-deficient tumor graft recipient mice. Conversely, melanoma-specific PD-1 overexpression enhances tumorigenicity, as does engagement of melanoma-PD-1 by its ligand, PD-L1, whereas melanoma-PD-L1 inhibition or knockout of host-PD-L1 attenuate growth of PD-1-positive melanomas. Mechanistically, themelanoma-PD-1 receptor modulates downstream effectors of mTOR signaling. Our results identify melanoma cell-intrinsic functions of the PD-1:PD-L1 axis in tumor growth and suggest that blocking melanoma-PD-1 might contribute to the striking clinical efficacy of anti-PD-1 therapy. C1 [Kleffel, Sonja; Posch, Christian; Barthel, Steven R.; Mueller, Hansgeorg; Elco, Christopher P.; Lee, Nayoung; Mihm, Martin C., Jr.; Frank, Markus H.; Kupper, Thomas S.; Schatton, Tobias] Harvard Univ, Sch Med, Dept Dermatol, Harvard Skin Dis Res Ctr,Brigham & Womens Hosp, Boston, MA 02115 USA. [Posch, Christian] Rudolfstiftung Hosp, Dept Dermatol, A-1030 Vienna, Austria. [Mueller, Hansgeorg] Med Univ Innsbruck, Dept Dermatol, A-6020 Innsbruck, Austria. [Schlapbach, Christoph; Thomi, Rahel] Univ Bern, Dept Dermatol, CH-3010 Bern, Switzerland. [Guenova, Emmanuella; Hoetzenecker, Wolfram; Cozzio, Antonio; Dummer, Reinhard] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. [Elco, Christopher P.; Zhan, Qian; Lian, Christine G.; Murphy, George F.; Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Juneja, Vikram R.; Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Flaherty, Keith T.] Harvard Univ, Sch Med, Div Med Oncol, Massachusetts Gen Hosp,Canc Ctr, Boston, MA 02114 USA. [Frank, Markus H.; Schatton, Tobias] Harvard Univ, Sch Med, Dept Med, Childrens Hosp Boston, Boston, MA 02115 USA. [Frank, Markus H.] Edith Cowan Univ, Sch Med Sci, Joondalup, WA 6027, Australia. [Sharpe, Arlene H.] Harvard Univ, Sch Med, Evergrande Ctr Immunol Dis, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Schatton, T (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Harvard Skin Dis Res Ctr,Brigham & Womens Hosp, Boston, MA 02115 USA. EM tschatton@bwh.harvard.edu OI Posch, Christian/0000-0003-0296-3567 FU Melanoma International Foundation; Brigham Research Institute; Brigham and Women's Hospital, Department of Dermatology; Swiss National Science Foundation [PMDPP3_151326]; NIH/NCI [1R01CA158467, U54 CA163125]; Dermatology Foundation; Austrian Society of Dermatology and Venereology; Fondation Rene Touraine; Outrun the Sun Melanoma Foundation; American Skin Association; Department of Defense through the National Defense Science and Engineering Graduate Fellowship (NDSEG) Program FX We thank M. Joubert, I. Portugal, C. Correia, and C. Lee for technical assistance. This work was supported by an Innovative Research Grant from the Melanoma International Foundation, a Fund to Sustain Research Excellence from the Brigham Research Institute, Brigham and Women's Hospital, Department of Dermatology funding for new investigators (to T.S.), a Swiss National Science Foundation grant PMDPP3_151326 (to E.G.), and NIH/NCI grants 1R01CA158467 (to M.H.F. and G.F.M.), and U54 CA163125 (to A.H.S.). T.S. is the recipient of a Research Career Development award from the Dermatology Foundation. C.P. and H.M. are recipients of a Klaus Wolff Fellowship by the Austrian Society of Dermatology and Venereology and received salary support from the Fondation Rene Touraine. C.P. was awarded a Melanoma Research Scholar Award from the Outrun the Sun Melanoma Foundation. N.L. is the recipient of a Medical Student Grant from the American Skin Association. V.R.J. is supported by the Department of Defense through the National Defense Science and Engineering Graduate Fellowship (NDSEG) Program. The authors declare that there are no conflicts of interest. NR 29 TC 40 Z9 46 U1 8 U2 43 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 SEP 10 PY 2015 VL 162 IS 6 BP 1242 EP 1256 DI 10.1016/j.cell.2015.08.052 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CR3QL UT WOS:000361247900015 PM 26359984 ER PT J AU Avraham, R Haseley, N Brown, D Penaranda, C Jijon, HB Trombetta, JJ Satija, R Shalek, AK Xavier, RJ Regev, A Hung, DT AF Avraham, Roi Haseley, Nathan Brown, Douglas Penaranda, Cristina Jijon, Humberto B. Trombetta, John J. Satija, Rahul Shalek, Alex K. Xavier, Ramnik J. Regev, Aviv Hung, Deborah T. TI Pathogen Cell-to-Cell Variability Drives Heterogeneity in Host Immune Responses SO CELL LA English DT Article ID 2-COMPONENT REGULATORY SYSTEM; ENTERICA SEROVAR TYPHIMURIUM; SALMONELLA-ENTERICA; SINGLE-CELL; GENE-EXPRESSION; INFLAMMASOME ACTIVATION; III SECRETION; PHOP-PHOQ; RNA-SEQ; MACROPHAGES AB Encounters between immune cells and invading bacteria ultimately determine the course of infection. These interactions are usually measured in populations of cells, masking cell-to-cell variation that may be important for infection outcome. To characterize the gene expression variation that underlies distinct infection outcomes and monitor infection phenotypes, we developed an experimental system that combines single-cell RNA-seq with fluorescent markers. Probing the responses of individual macrophages to invading Salmonella, we find that variation between individual infected host cells is determined by the heterogeneous activity of bacterial factors in individual infecting bacteria. We illustrate how variable PhoPQ activity in the population of invading bacteria drives variable host type I IFN responses by modifying LPS in a subset of bacteria. This work demonstrates a causative link between host and bacterial variability, with cell-to-cell variation between different bacteria being sufficient to drive radically different host immune responses. This co-variation has implications for host-pathogen dynamics in vivo. C1 [Avraham, Roi; Haseley, Nathan; Brown, Douglas; Trombetta, John J.; Satija, Rahul; Shalek, Alex K.; Xavier, Ramnik J.; Regev, Aviv; Hung, Deborah T.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Haseley, Nathan] MIT, Dept Hlth Sci & Technol, Cambridge, MA 02139 USA. [Penaranda, Cristina; Hung, Deborah T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Jijon, Humberto B.; Xavier, Ramnik J.; Hung, Deborah T.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Jijon, Humberto B.] Univ Calgary, Div Gastroenterol, Dept Med, Calgary, AB T2N 1N4, Canada. [Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Ctr Study Inflammatory Bowe, Boston, MA 02114 USA. [Regev, Aviv] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA. [Hung, Deborah T.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. RP Hung, DT (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. EM hung@molbio.mgh.harvard.edu OI Avraham, Roi/0000-0002-9098-3885 FU NIH [HG002295, DK043351, U19AI109725, F32 HD075541-02]; NHGRI Center of Excellence in Genome Science (CEGS) Center of Cell Circuits [P50 HG006193]; Klarman Cell Observatory FX We thank Alan Grossman, Dan Kahne, Jon Kagan, Nir Hacohen, Itai Yanai, and Amy Barczak for discussions and comments. We thank Eduardo Villablanca for advice with in vivo experiments. We thank Ken Livak for help with Biomark experiments. We thank Leslie Gafney for help with graphical illustrations and figures. This work was supported by NIH grants (HG002295 to N.H.; DK043351 and U19AI109725 to R.J.X.; and F32 HD075541-02 to R.S.) and the NHGRI Center of Excellence in Genome Science (CEGS) Center of Cell Circuits (P50 HG006193) (to A.R.). A.R. was supported by the Klarman Cell Observatory. A.R. is a member of the Scientific Advisory Board of Thermo Fisher Scientific and Syros Pharmaceutical and is a consultant for Driver Group. NR 34 TC 32 Z9 34 U1 3 U2 34 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 SEP 10 PY 2015 VL 162 IS 6 BP 1309 EP 1321 DI 10.1016/j.cell.2015.08.027 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CR3QL UT WOS:000361247900020 PM 26343579 ER PT J AU Jamieson, C Hasserjian, R Gotlib, J Cortes, J Stone, R Talpaz, M Thiele, J Rodig, S Pozdnyakova, O AF Jamieson, Catriona Hasserjian, Robert Gotlib, Jason Cortes, Jorge Stone, Richard Talpaz, Moshe Thiele, Juergen Rodig, Scott Pozdnyakova, Olga TI Effect of treatment with a JAK2-selective inhibitor, fedratinib, on bone marrow fibrosis in patients with myelofibrosis SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article DE Fibrosis; Janus kinase inhibitor; Myelofibrosis; Myeloproliferative neoplasms; Philadelphia chromosome-negative ID CHRONIC IDIOPATHIC MYELOFIBROSIS; INTERNATIONAL-WORKING-GROUP; STEM-CELL TRANSPLANTATION; POLYCYTHEMIA-VERA; MYELOPROLIFERATIVE NEOPLASMS; EUROPEAN CONSENSUS; ERYTHROID-DIFFERENTIATION; ESSENTIAL THROMBOCYTHEMIA; RETICULIN FIBROSIS; MYELOID METAPLASIA AB Background: Progressive bone marrow fibrosis (BMF) is a cardinal feature of many myeloproliferative neoplasms (MPNs) and there is a documented association between the severity of BMF and overall prognosis. We conducted an exploratory analysis of sequential BMF data from two phase I studies of long-term treatment with the Janus kinase 2 (JAK2) inhibitor fedratinib in patients with myelofibrosis. Methods: Bone marrow samples were obtained at baseline and after every six cycles (24 weeks) of daily fedratinib treatment. Fibrosis was centrally assessed by three independent haematopathologists, who were blinded to the patients' data, and graded according to European Consensus Myelofibrosis Grading Criteria. The analysis population comprised patients with a baseline BMF grade >= 1, and at least one post-baseline BMF grade assessment. Changes in BMF grade compared with baseline were classified as improvement (>= 1 grade reduction), stabilisation (no change in any baseline BMF grade <3) or worsening (>= 1 grade increase). Results: Twenty-one patients were included in the analysis. A total of 153 bone marrow samples were analysed. Improvement or stabilisation of BMF from baseline was recorded in 15 of 18 (83 %) evaluable patients at cycle 6 and in four of nine (44 %) evaluable patients at cycle 30. Two patients achieved resolution of their BMF (grade = 0) by cycle 12. Conclusions: This exploratory analysis indicates that improvement or even resolution of BMF may be achievable with JAK2 inhibitor therapy in some patients with MPNs and myelofibrosis. C1 [Jamieson, Catriona] Moores UC San Diego Canc Ctr, La Jolla, CA 92093 USA. [Hasserjian, Robert] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Gotlib, Jason] Stanford Univ, Sch Med, Stanford Canc Inst, Div Hematol, Stanford, CA 94305 USA. [Cortes, Jorge] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Div Canc Med, Houston, TX 77030 USA. [Stone, Richard] Dana Farber Canc Inst, Boston, MA 02215 USA. [Talpaz, Moshe] Univ Michigan Hosp & Hlth Syst, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Thiele, Juergen] Univ Cologne, Inst Pathol, D-50924 Cologne, Germany. [Rodig, Scott; Pozdnyakova, Olga] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Jamieson, C (reprint author), Moores UC San Diego Canc Ctr, 3855 Hlth Sci Dr, La Jolla, CA 92093 USA. EM cjamieson@ucsd.edu FU Sanofi FX Writing assistance was provided by Neil Anderson, PhD from Adelphi Communications Ltd, and funded by Sanofi. NR 33 TC 1 Z9 2 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD SEP 10 PY 2015 VL 13 AR 294 DI 10.1186/s12967-015-0644-4 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CR0QZ UT WOS:000361029500001 PM 26357842 ER PT J AU Kim, T Ramesh, V Dworak, M Choi, DS Mccarley, RW Kalinchuk, AV Basheer, R AF Kim, T. Ramesh, V. Dworak, M. Choi, D. -S. Mccarley, R. W. Kalinchuk, A. V. Basheer, R. TI DISRUPTED SLEEP-WAKE REGULATION IN TYPE 1 EQUILIBRATIVE NUCLEOSIDE TRANSPORTER KNOCKOUT MICE SO NEUROSCIENCE LA English DT Article DE adenosine; basal forebrain; sleep deprivation; sleep homeostasis; NREM delta; wake-theta ID BASAL FOREBRAIN NEURONS; NITRIC-OXIDE PRODUCTION; PROLONGED WAKEFULNESS; RECOVERY SLEEP; CHOLINERGIC NEURONS; THETA ACTIVITY; WAKING EEG; ADENOSINE; BRAIN; HOMEOSTASIS AB The type 1 equilibrative nucleoside transporter (ENT1) is implicated in regulating levels of extracellular adenosine ([AD](ex)). In the basal forebrain (BF) levels of [AD](ex) increase during wakefulness and closely correspond to the increases in the electroencephalogram (EEG) delta (0.75-4.5 Hz) activity (NR delta) during subsequent non-rapid eye movement sleep (NREMS). Thus in the BF, [AD](ex) serves as a biochemical marker of sleep homeostasis. Waking EEG activity in theta range (5-9 Hz, W theta) is also described as a marker of sleep homeostasis. An hour-by-hour temporal relationship between the W theta and NR delta is unclear. In this study we examined the relationship between these EEG markers of sleep homeostasis during spontaneous sleepwakefulness and during sleep deprivation (SD) and recovery sleep in the ENT1 gene knockout (ENT1KO) mouse. We observed that baseline NREMS amount was decreased during the light period in ENT1KO mice, accompanied by a weak correlation between W theta of each hour and NR delta of its subsequent hour when compared to their wild-type (WT) littermates. Perfusion of low dose of adenosine into BF not only strengthened the Wh-NRd relationship, but also increased NREMS to match with the WT littermates suggesting decreased [AD](ex) in ENT1KO mice. However, the SDinduced [AD](ex) increase in the BF and the linear correlation between the EEG markers of sleep homeostasis were unaffected in ENT1KO mice suggesting that during SD, sources other than ENT1 contribute to increase in [AD](ex). Our data provide evidence for a differential regulation of wakefulness-associated [AD](ex) during spontaneous vs prolonged waking. Published by Elsevier Ltd. on behalf of IBRO. C1 [Kim, T.; Ramesh, V.; Dworak, M.; Mccarley, R. W.; Kalinchuk, A. V.; Basheer, R.] VA Boston Healthcare Syst, West Roxbury, MA 02132 USA. [Kim, T.; Ramesh, V.; Dworak, M.; Mccarley, R. W.; Kalinchuk, A. V.; Basheer, R.] Harvard Univ, Sch Med, West Roxbury, MA 02132 USA. [Choi, D. -S.] Mayo Clin, Coll Med, Dept Mol Pharmacol & Expt Therapeut, Mol Neurosci Program, Rochester, MN 55905 USA. RP Basheer, R (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM Radhika_Basheer@hms.harvard.edu RI Choi, Doo-Sup/G-9474-2012 FU Department of Veterans Affairs Medical Research Service Merit Award; NINDS [079866]; NIMH [39683, 099180]; NIAAA [018779] FX The work was supported by the Department of Veterans Affairs Medical Research Service Merit Award to RB and RWM, NINDS 079866 (RB), NIMH 39683 (RWM), NIAAA 018779 (DSC), NIMH 099180 (AVK). We thank Mrs. Farzana Pervin for excellent technical assistance and Diane Ghera and Dewayne Williams for help with animal care. The authors declare no competing financial interests. NR 35 TC 2 Z9 2 U1 0 U2 5 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 SEP 10 PY 2015 VL 303 BP 211 EP 219 DI 10.1016/j.neuroscience.2015.06.037 PG 9 WC Neurosciences SC Neurosciences & Neurology GA CO5NZ UT WOS:000359207100019 PM 26143012 ER PT J AU Moody, MA Gao, F Gurley, TC Amos, JD Kumar, A Hora, B Marshall, DJ Whitesides, JF Xia, SM Parks, R Lloyd, KE Hwang, KK Lu, XZ Bonsignori, M Finzi, A Vandergrift, NA Alam, SM Ferrari, G Shen, XY Tomaras, GD Kamanga, G Cohen, MS Sam, NE Kapiga, S Gray, ES Tumba, NL Morris, L Zolla-Pazner, S Gorny, MK Mascola, JR Hahn, BH Shaw, GM Sodroski, JG Liao, HX Montefiori, DC Hraber, PT Korber, BT Haynes, BF AF Moody, M. Anthony Gao, Feng Gurley, Thaddeus C. Amos, Joshua D. Kumar, Amit Hora, Bhavna Marshall, Dawn J. Whitesides, John F. Xia, Shi-Mao Parks, Robert Lloyd, Krissey E. Hwang, Kwan-Ki Lu, Xiaozhi Bonsignori, Mattia Finzi, Andres Vandergrift, Nathan A. Alam, S. Munir Ferrari, Guido Shen, Xiaoying Tomaras, Georgia D. Kamanga, Gift Cohen, Myron S. Sam, Noel E. Kapiga, Saidi Gray, Elin S. Tumba, Nancy L. Morris, Lynn Zolla-Pazner, Susan Gorny, Miroslaw K. Mascola, John R. Hahn, Beatrice H. Shaw, George M. Sodroski, Joseph G. Liao, Hua-Xin Montefiori, David C. Hraber, Peter T. Korber, Bette T. Haynes, Barton F. TI Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses SO CELL HOST & MICROBE LA English DT Article ID MONOCLONAL-ANTIBODIES; GLYCOPROTEIN GP120; NAIVE INDIVIDUALS; INFECTION; RESPONSES; ENVELOPE; EVOLUTION; VACCINE; ESCAPE; PATHWAYS AB The third variable (V3) loop and the CD4 binding site (CD4bs) of the HIV-1 envelope are frequently targeted by neutralizing antibodies (nAbs) in infected individuals. In chronic infection, HIV-1 escape mutants repopulate the plasma, and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to-neutralize but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3 and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tier 2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs anti-bodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses. C1 [Moody, M. Anthony; Gao, Feng; Gurley, Thaddeus C.; Amos, Joshua D.; Kumar, Amit; Hora, Bhavna; Marshall, Dawn J.; Whitesides, John F.; Xia, Shi-Mao; Parks, Robert; Lloyd, Krissey E.; Hwang, Kwan-Ki; Lu, Xiaozhi; Bonsignori, Mattia; Vandergrift, Nathan A.; Alam, S. Munir; Ferrari, Guido; Shen, Xiaoying; Tomaras, Georgia D.; Morris, Lynn; Liao, Hua-Xin; Haynes, Barton F.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27710 USA. [Moody, M. Anthony] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. [Moody, M. Anthony; Tomaras, Georgia D.; Haynes, Barton F.] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA. [Gao, Feng; Vandergrift, Nathan A.; Alam, S. Munir; Liao, Hua-Xin; Haynes, Barton F.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Alam, S. Munir; Montefiori, David C.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [Ferrari, Guido; Tomaras, Georgia D.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Finzi, Andres] Univ Montreal, CHUM, Ctr Rech, Montreal, PQ H2X 0A9, Canada. [Finzi, Andres] Univ Montreal, Dept Microbiol Infectol & Immunol, Montreal, PQ H2X 0A9, Canada. [Finzi, Andres] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H2X 1P1, Canada. [Kamanga, Gift] Univ North Carolina Project, Kamuzu Cent Hosp, Lilongwe, Malawi. [Cohen, Myron S.] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA. [Cohen, Myron S.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Cohen, Myron S.] Univ N Carolina, Dept Microbiol, Chapel Hill, NC 27599 USA. [Cohen, Myron S.] Univ N Carolina, Dept Immunol, Chapel Hill, NC 27599 USA. [Sam, Noel E.] Kilimanjaro Christian Med Ctr, Moshi 25102, Tanzania. [Kapiga, Saidi] Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England. [Gray, Elin S.; Tumba, Nancy L.; Morris, Lynn] Natl Inst Communicable Dis, ZA-2131 Johannesburg, South Africa. [Zolla-Pazner, Susan; Gorny, Miroslaw K.] NYU, Sch Med, Dept Pathol, New York, NY 10010 USA. [Zolla-Pazner, Susan] Vet Affairs New York Harbor Healthcare Syst, New York, NY 10010 USA. [Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Hahn, Beatrice H.; Shaw, George M.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Sodroski, Joseph G.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Hraber, Peter T.; Korber, Bette T.] Los Alamos Natl Lab, Los Alamos, NM 87545 USA. RP Moody, MA (reprint author), Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27710 USA. EM moody007@mc.duke.edu; feng.gao@dm.duke.edu; hayne002@mc.duke.edu RI Tomaras, Georgia/J-5041-2016; OI Korber, Bette/0000-0002-2026-5757; , Lynn/0000-0003-3961-7828; Gorny, Miroslaw/0000-0002-2714-8780; Hraber, Peter/0000-0002-2920-4897; Gray, Elin/0000-0002-8613-3570 FU Bill and Melinda Gates Foundation; Center for HIV/AIDS Vaccine Immunology (CHAVI) [U19 AI067854]; Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery grant (CHAVI-ID) [UM1 AI100645]; CAVD [OPP1032325]; Duke Center for AIDS Research Flow Cytometry and Virology cores (CFAR) [P30-AI-64518]; NIH [P01 AI 100151]; Department of Veterans Affairs FX We regret that due to space limitations we were unable to cite many excellent papers of our colleagues. HJ16 was generously donated by Davide Corti (Institute for Research in Biomedicine, Bellinzona, Switzerland). Support was provided by a Collaboration for AIDS Vaccine Discovery grant to B.F.H. from the Bill and Melinda Gates Foundation, the Center for HIV/AIDS Vaccine Immunology (CHAVI; grant U19 AI067854), and the Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery grant (CHAVI-ID; grant UM1 AI100645). Further support was provided by CAVD funding for the CTVIMC, grant number OPP1032325; the Duke Center for AIDS Research Flow Cytometry and Virology cores (CFAR; P30-AI-64518); NIH grant P01 AI 100151 (S.Z.-P.); and funds from the Department of Veterans Affairs. We thank Daniel M. Kozink, Florence Perrin, and Abby J. Cooper for expert technical support. NR 33 TC 15 Z9 15 U1 2 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 EI 1934-6069 J9 CELL HOST MICROBE JI Cell Host Microbe PD SEP 9 PY 2015 VL 18 IS 3 BP 354 EP 362 DI 10.1016/j.chom.2015.08.006 PG 9 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA CR3RA UT WOS:000361249400013 PM 26355218 ER PT J AU Balbale, SN Hill, JN Guihan, M Hogan, TP Cameron, KA Goldstein, B Evans, CT AF Balbale, Salva N. Hill, Jennifer N. Guihan, Marylou Hogan, Timothy P. Cameron, Kenzie A. Goldstein, Barry Evans, Charlesnika T. TI Evaluating implementation of methicillin-resistant Staphylococcus aureus (MRSA) prevention guidelines in spinal cord injury centers using the PARIHS framework: a mixed methods study SO IMPLEMENTATION SCIENCE LA English DT Article ID CONCEPTUAL-FRAMEWORK; QUALITATIVE RESEARCH; UNITED-STATES; VETERANS; INFECTIONS; HOSPITALIZATIONS; EPIDEMIOLOGY; DISORDER; CONTEXT; BUNDLE AB Background: To prevent methicillin-resistant Staphylococcus aureus (MRSA) in Spinal Cord Injury and Disorder (SCI/D) Centers, the "Guidelines for Implementation of MRSA Prevention Initiative in the Spinal Cord Injury Centers" were released in July 2008 in the Veterans Affairs (VA) Health Care System. The purpose of this study was to use the Promoting Action on Research Implementation in Health Systems (PARiHS) framework to evaluate the experiences of implementation of SCI/D MRSA prevention guidelines in VA SCI/D Centers approximately 2-3 years after the guidelines were released. Methods: Mixed methods were used across two phases in this study. The first phase included an anonymous, web-based cross-sectional survey administered to providers at all 24 VA SCI/D Centers. The second phase included semi-structured telephone interviews with providers at 9 SCI/D Centers. The PARiHS framework was used as the foundation of both the survey questions and semi-structured interview guide. Results: The survey was completed by 295 SCI/D providers (43.8 % response rate) from 22 of the 24 SCI/D Centers (91.7 % participation rate). Respondents included nurses (57.3 %), therapists (24.4 %), physicians (11.1 %), physician assistants (3.4 %), and other health care professionals (3.8 %). Approximately 36 % of the SCI/D providers surveyed had not seen, did not remember seeing, or had never heard of the MRSA SCI/D guidelines, whereas 42.3 % of providers reported that the MRSA SCI/D guidelines were fully implemented in their SCI/D Center. Data revealed numerous barriers and facilitators to guideline implementation. Facilitators included enhanced leadership support and provider education, focused guideline dissemination to reach SCI/D providers, and strong perceived evidence supporting the guidelines. Barriers included lack of awareness of the guidelines among physical therapists and physician assistants and challenges in cohorting/isolating MRSA-positive patients and following contact precautions. Conclusions: Successful implementation of MRSA infection prevention guidelines in SCI/D settings requires (1) guideline dissemination that reaches the full range of SCI/D providers working in inpatient, outpatient, and other care settings, (2) provider education that is frequent and systematic, (3) strong leadership support, and (4) that barriers unique to the recommendations are addressed. These findings may be used to inform selection of implementation strategies and optimize infection prevention beyond MRSA as well as in other specialty care populations. C1 [Balbale, Salva N.; Hill, Jennifer N.; Guihan, Marylou; Evans, Charlesnika T.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Spinal Cord Injury Qual Enhancement Res Initiat, Hines, IL 60141 USA. [Balbale, Salva N.; Hill, Jennifer N.; Guihan, Marylou; Evans, Charlesnika T.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Innovat Complex Chron Healthcare, Hines, IL 60141 USA. [Balbale, Salva N.; Evans, Charlesnika T.] Northwestern Univ, Ctr Healthcare Studies, Inst Publ Hlth & Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Guihan, Marylou] Northwestern Univ, Dept Phys Med & Rehabil, Feinberg Sch Med, Chicago, IL 60611 USA. [Hogan, Timothy P.] US Dept Vet Affairs, Ctr Healthcare Org & Implementat Res, Edith Nourse Rogers Mem Vet Hosp, Bedford, MA USA. [Hogan, Timothy P.] US Dept Vet Affairs, 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, Div Hlth Informat & Implementat Sci, Dept Quantitat Hlth Sci, Worcester, MA USA. [Cameron, Kenzie A.] Northwestern Univ, Dept Med, Div Gen Internal Med & Geriatr, Feinberg Sch Med, Chicago, IL 60611 USA. [Cameron, Kenzie A.; Evans, Charlesnika T.] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Goldstein, Barry] US Dept Vet Affairs, Patient Care Serv, Spinal Cord Injury Disorders Serv, Seattle, WA USA. [Goldstein, Barry] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP Evans, CT (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Spinal Cord Injury Qual Enhancement Res Initiat, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. EM Charlesnika.Evans@va.gov FU Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development Service, Quality Enhancement Research Initiative [RRP-09-163] FX The views expressed in this article are those of the authors and do not necessarily represent the views of the US Department of Veterans Affairs. This study was supported by the Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development Service, Quality Enhancement Research Initiative (RRP-09-163). NR 42 TC 3 Z9 3 U1 1 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD SEP 9 PY 2015 VL 10 AR 130 DI 10.1186/s13012-015-0318-x PG 15 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CQ9SX UT WOS:000360956500001 PM 26353798 ER PT J AU Moreno-Ramos, OA Olivares, AM Haider, NB de Autismo, LC Lattig, MC AF Moreno-Ramos, Oscar A. Maria Olivares, Ana Haider, Neena B. Colombiana de Autismo, Liga Claudia Lattig, Maria TI Whole-Exome Sequencing in a South American Cohort Links ALDH1A3, FOXN1 and Retinoic Acid Regulation Pathways to Autism Spectrum Disorders SO PLOS ONE LA English DT Article ID DE-NOVO MUTATIONS; EXONIC SPLICING ENHANCERS; SYNONYMOUS VARIANTS; MISSENSE MUTATIONS; GENE-EXPRESSION; GENOME; GENERATION; DNA; ANOPHTHALMIA/MICROPHTHALMIA; IDENTIFICATION AB Autism spectrum disorders (ASDs) are a range of complex neurodevelopmental conditions principally characterized by dysfunctions linked to mental development. Previous studies have shown that there are more than 1000 genes likely involved in ASD, expressed mainly in brain and highly interconnected among them. We applied whole exome sequencing in Colombian-South American trios. Two missense novel SNVs were found in the same child: ALDH1A3 (RefSeq NM_000693: c.1514T>C (p.I505T)) and FOXN1 (RefSeq NM_003593: c. 146C>T (p.S49L)). Gene expression studies reveal that Aldh1a3 and Foxn1 are expressed in similar to E13.5 mouse embryonic brain, as well as in adult piriform cortex (PC; similar to P30). Conserved Retinoic Acid Response Elements (RAREs) upstream of human ALDH1A3 and FOXN1 and in mouse Aldh1a3 and Foxn1 genes were revealed using bioinformatic approximation. Chromatin immunoprecipitation (ChIP) assay using Retinoid Acid Receptor B (Rarb) as the immunoprecipitation target suggests RA regulation of Aldh1a3 and Foxn1 in mice. Our results frame a possible link of RA regulation in brain to ASD etiology, and a feasible non-additive effect of two apparently unrelated variants in ALDH1A3 and FOXN1 recognizing that every result given by next generation sequencing should be cautiously analyzed, as it might be an incidental finding. C1 [Moreno-Ramos, Oscar A.; Claudia Lattig, Maria] Univ Los Andes, Fac Ciencias, Dept Ciencias Biol, Bogota, Colombia. [Maria Olivares, Ana; Haider, Neena B.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA USA. [Colombiana de Autismo, Liga] Liga Colombiana Autismo LICA, Bogota, Colombia. RP Lattig, MC (reprint author), Univ Los Andes, Fac Ciencias, Dept Ciencias Biol, Bogota, Colombia. EM mlattig@uniandes.edu.co NR 65 TC 2 Z9 2 U1 1 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 9 PY 2015 VL 10 IS 9 AR e0135927 DI 10.1371/journal.pone.0135927 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ9KG UT WOS:000360932800019 PM 26352270 ER PT J AU Nwachukwu, BU Gurary, EB Lerner, V Collins, JE Thornhill, TS Losina, E Katz, JN AF Nwachukwu, Benedict U. Gurary, Ellen B. Lerner, Vladislav Collins, Jamie E. Thornhill, Thomas S. Losina, Elena Katz, Jeffrey N. TI Effect of smoking and soft tissue release on risk of revision after total knee arthroplasty: a case-control study SO BMC MUSCULOSKELETAL DISORDERS LA English DT Article ID UNITED-STATES; REPLACEMENT; RATES; COMPLICATIONS; POPULATION; SURGERY; EVENTS; HIP AB Background: Increasing utilization of primary total knee arthroplasty (TKA) is projected to expand demand for revision TKA. Revision TKAs are procedurally complex and incur high costs on our financially constrained healthcare system. The purpose of this study was to use a case-control design to identify factors predisposing to revision TKA, particularly demographic, clinical and perioperative technical factors. Methods: We conducted a case control study to investigate patient, surgical and perioperative factors associated with greater risk of revision TKA. We included patients who received TKA at a tertiary center between 1996 and 2009. Cases (patients that had primary and revision TKA) were matched to controls (patients with primary TKA that was not revised) in a 1:2 ratio and risk of revision examined using conditional logistic regression. Results: We identified 146 cases and 290 controls. Patient factors independently associated with revision included male sex (OR 1.73; 95 % CI 1.06-2.81) and smoking (OR 2.87; 1.33-6.19). Older age was associated with decreased risk (OR 0.83 per 5-year increment; 95 % CI 0.75-0.92). Lateral release was the only technical factor associated with revision (OR 1.92; 1.07-3.43). Conclusions: In this case control study younger patient age, male gender, soft tissue release and active smoking status were associated with increased revision risk. Although we do not know whether the risk of smoking arises from short- or long-term exposure, smoking cessation prior to TKA should be considered as an intervention for decreasing revision risk. C1 [Losina, Elena; Katz, Jeffrey N.] Div Rheumatol Immunol & Allergy, Boston, MA USA. [Nwachukwu, Benedict U.] Hosp Special Surg, Dept Orthoped Surg, New York, NY 10021 USA. [Lerner, Vladislav] Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. [Gurary, Ellen B.; Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Katz, Jeffrey N.] Brigham & Womens Hosp, Orthoped & Arthrit Ctr Outcomes Res, Boston, MA 02115 USA. EM jnkatz@partners.org FU Pilot Research Incubation and Development Program (PRIDE) through the Department of Orthopaedic Surgery at Brigham & Women's Hospital; NIAMS [T32AR055885] FX This work was supported by the Pilot Research Incubation and Development Program (PRIDE) through the Department of Orthopaedic Surgery at Brigham & Women's Hospital as well as NIAMS T32AR055885. NR 28 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2474 J9 BMC MUSCULOSKEL DIS JI BMC Musculoskelet. Disord. PD SEP 9 PY 2015 VL 16 AR 245 DI 10.1186/s12891-015-0694-z PG 6 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA CQ8RY UT WOS:000360877300002 PM 26353801 ER PT J AU Peeters, M van Rijn, S Vergroesen, PPA Paul, CPL Noske, DP Vandertop, WP Wurdinger, T Helder, MN AF Peeters, Mirte van Rijn, Sjoerd Vergroesen, Pieter-Paul A. Paul, Cornelis P. L. Noske, David P. Vandertop, W. Peter Wurdinger, Thomas Helder, Marco N. TI Bioluminescence-mediated longitudinal monitoring of adipose-derived stem cells in a large mammal ex vivo organ culture SO SCIENTIFIC REPORTS LA English DT Article ID IN-VIVO; INTERVERTEBRAL DISC; TISSUE; LUCIFERASE; DIFFERENTIATION; TRANSPLANTATION; DEGENERATION; REGENERATION; MECHANISM; CARTILAGE AB Recently, ex vivo three-dimensional organ culture systems have emerged to study the physiology and pathophysiology of human organs. These systems also have potential as a translational tool in tissue engineering; however, this potential is limited by our ability to longitudinally monitor the fate and action of cells used in regenerative therapies. Therefore, we investigated luciferase-mediated bioluminescence imaging (BLI) as a non-invasive technique to continuously monitor cellular behavior in ex vivo whole organ culture. Goat adipose-derived stem cells (gADSCs) were transduced with either Firefly luciferase (Fluc) or Gaussia luciferase (Gluc) reporter genes and injected in isolated goat intervertebral discs (IVD). Luciferase activity was monitored by BLI for at least seven days of culture. Additionally, possible confounders specific to avascular organ culture were investigated. Gluc imaging proved to be more suitable compared to Fluc in monitoring gADSCs in goat IVDs. We conclude that BLI is a promising tool to monitor spatial and temporal cellular behavior in ex vivo organ culture. Hence, ex vivo organ culture systems allow pre-screening and pre-validation of novel therapeutic concepts prior to in vivo large animal experimentation. Thereby, organ culture systems can reduce animal use, and improve the speed of innovation by overcoming technological, ethical and financial challenges. C1 [Peeters, Mirte; Vergroesen, Pieter-Paul A.; Paul, Cornelis P. L.; Helder, Marco N.] Vrije Univ Amsterdam Med Ctr, Dept Orthoped Surg, MOVE Res Inst Amsterdam, Amsterdam, Netherlands. [van Rijn, Sjoerd; Noske, David P.; Vandertop, W. Peter; Wurdinger, Thomas] Vrije Univ Amsterdam Med Ctr, Dept Neurosurg, Amsterdam, Netherlands. [Wurdinger, Thomas] Massachusetts Gen Hosp, Dept Neurol, Ctr Neurosci, Boston, MA 02114 USA. [Wurdinger, Thomas] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. RP Helder, MN (reprint author), Vrije Univ Amsterdam Med Ctr, Dept Orthoped Surg, MOVE Res Inst Amsterdam, Amsterdam, Netherlands. EM m.helder@vumc.nl RI Peeters, Mirte/M-8607-2015 OI Peeters, Mirte/0000-0002-5197-1312 FU European Commission (FP7 project "NPmimetic") [246351]; CCA/VICI Fellowships; NWO-VIDI grants FX We like to thank Willem de Jong for preparation and processing of tissue sections, Klaas Walter Meyer and Paul Sinnige for assistance in the preparation of the experiments and Alan Brind for proofreading the manuscript. Funding for this study was provided by the European Commission (FP7 project "NPmimetic"; Grant number #246351) (MP), CCA/VICI Fellowships (SvR) and NWO-VIDI grants (TW). NR 43 TC 0 Z9 0 U1 4 U2 13 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 SEP 9 PY 2015 VL 5 AR 13960 DI 10.1038/srep13960 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ9AR UT WOS:000360903400001 PM 26350622 ER PT J AU Narayanaswami, P Dubinsky, R Wang, D Gjorvad, G David, W Finder, J Smith, B Cheng, JG Shapiro, F Mellion, M Spurney, C Wolff, J England, J AF Narayanaswami, Pushpa Dubinsky, Richard Wang, David Gjorvad, Gina David, William Finder, Jonathan Smith, Benn Cheng, Jianguo Shapiro, Frederic Mellion, Michelle Spurney, Christopher Wolff, Jodi England, John TI Quality improvement in neurology Muscular dystrophy quality measures SO NEUROLOGY LA English DT Article ID GUIDELINE DEVELOPMENT SUBCOMMITTEE; AMERICAN ACADEMY; OF-LIFE; ELECTRODIAGNOSTIC MEDICINE; STANDARDS SUBCOMMITTEE; NEUROMUSCULAR DISEASE; PRACTICE PARAMETER; DUCHENNE; CARE; MANAGEMENT C1 [Narayanaswami, Pushpa] Harvard Univ, Sch Med, Beth Israel Deaconess, Boston, MA USA. [Dubinsky, Richard] Univ Kansas, Kansas City, KS USA. [Wang, David] Order St Francis Hlth Care, Peoria, IL USA. [Gjorvad, Gina] Amer Acad Neurol, Minneapolis, MN USA. [David, William] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Finder, Jonathan] Childrens Home Pittsburgh, Pittsburgh, PA USA. [Smith, Benn] Mayo Clin Scottsdale, Scottsdale, AZ USA. [Cheng, Jianguo] Cleveland Clin, Cleveland, OH USA. [Shapiro, Frederic] Harvard Univ, Sch Med, Boston Childrens Hosp, Cambridge, MA 02138 USA. [Mellion, Michelle] Neurol Fdn, Cambridge, MA USA. [Spurney, Christopher] George Washington Univ, Childrens Natl Med Ctr, Washington, DC USA. [Wolff, Jodi] Muscular Dystrophy Assoc, Tempe, AZ USA. [England, John] Louisiana State Univ, New Orleans Sch Med, Baton Rouge, LA 70803 USA. RP Gjorvad, G (reprint author), Amer Acad Neurol, Minneapolis, MN USA. EM quality@aan.com FU MERZ Pharmaceuticals; NIH; AHRQ for clinical research studies; National Institute of Neurological Disorders and Stroke, NIH, and HHS; Muscular Dystrophy Association of New Zealand; Parent Project Muscular Dystrophy; Muscular Dystrophy Association of Western Australia FX P. Narayanaswami serves on the Blue Cross Blue Shield of Massachusetts Pharmacy and Therapeutics Committee; serves as a consultant for both Advanced Medical and Boston Clinical Research Institute; and has received funding from MERZ Pharmaceuticals, NIH, and AHRQ for clinical research studies. R. Dubinsky serves on an advisory board for Allergan Pharmaceuticals on the treatment of cervical dystonia and chronic daily headache and has received honoraria and travel from them for speaking engagements; and has received funding from the National Institute of Neurological Disorders and Stroke, NIH, and HHS for 3 clinical research studies. D. Wang serves on the speaker's bureau of BMS and Boehringer-Ingelheim. G. Gjorvad reports no disclosures relevant to the manuscript. W. David has been involved in the production of a video CME course on EMG and neuromuscular medicine. J. Finder has delivered lectures and received travel paid by the Muscular Dystrophy Association of New Zealand, Parent Project Muscular Dystrophy, and Muscular Dystrophy Association of Western Australia; served as a peer reviewer for several medical journals and as an unpaid board member of RT magazine; and has served as a defense consultant on a non-neuromuscular disease case (no affidavit or testimony was provided). B. Smith has received compensation and travel for Grand Rounds at the University of Vermont for lectures on Autonomic Physiology and Clinical Neurophysiology. J. Cheng has served in an editorial capacity at the following publications: Pain Practice, World Journal of Anesthesiology, and Journal of Perioperative Science; is the inventor of 3 devices for pain management, 2 of which have been submitted for patent; is an editor of the textbook Fundamentals of Pain Medicine; has received compensation from the Taiwan Pain Society for lectures he delivered; and has received funding from the NIH on 3 clinical trials involving pain management. F. Shapiro receives royalties from Elsevier Publishers for a book published in 2002. M. Mellion received funding for 3 studies on peripheral neuropathy. C. Spurney serves on a scientific advisory board for Nicox. J. Wolff reports no disclosures relevant to the manuscript. J. England serves as the Editor-in-Chief of the Journal of the Neurological Sciences. Go to Neurology.org for full disclosures. NR 34 TC 1 Z9 1 U1 2 U2 2 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 SEP 8 PY 2015 VL 85 IS 10 BP 905 EP 909 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA DE3EF UT WOS:000370509100014 PM 26333798 ER PT J AU Mitsuhashi, K Yamamoto, I Kurihara, H Kanno, S Ito, M Igarashi, H Ishigami, K Sukawa, Y Tachibana, M Takahashi, H Tokino, T Maruyama, R Suzuki, H Imai, K Shinomura, Y Yamamoto, H Nosho, K AF Mitsuhashi, Kei Yamamoto, Itaru Kurihara, Hiroyoshi Kanno, Shinichi Ito, Miki Igarashi, Hisayoshi Ishigami, Keisuke Sukawa, Yasutaka Tachibana, Mami Takahashi, Hiroaki Tokino, Takashi Maruyama, Reo Suzuki, Hiromu Imai, Kohzoh Shinomura, Yasuhisa Yamamoto, Hiroyuki Nosho, Katsuhiko TI Analysis of the molecular features of rectal carcinoid tumors to identify new biomarkers that predict biological malignancy SO ONCOTARGET LA English DT Article DE carcinoid; non-coding RNA; epigenetics; neuroendocrine tumor; rectum ID ISLAND METHYLATOR PHENOTYPE; COLORECTAL-CANCER SURVIVAL; BRAF MUTATION; CLINICOPATHOLOGICAL FEATURES; POOR-PROGNOSIS; COLON-CANCER; MICROSATELLITE INSTABILITY; OVARIAN CARCINOMAS; SERRATED LESIONS; DNA METHYLATION AB Although gastrointestinal carcinoid tumors are relatively rare in the digestive tract, a quarter of them are present in the rectum. In the absence of specific tumor biomarkers, lymphatic or vascular invasion is generally used to predict the risk of lymph node metastasis. We, therefore, examined the genetic and epigenetic alterations potentially associated with lymphovascular invasion among 56 patients with rectal carcinoid tumors. We also conducted a microRNA (miRNA) array analysis. Our analysis failed to detect mutations in BRAF, KRAS, NRAS, or PIK3CA or any microsatellite instability (MSI); however, we did observe CpG island methylator phenotype (CIMP) positivity in 13% (7/56) of the carcinoid tumors. The CIMP-positive status was significantly correlated with lymphovascular invasion (P = 0.036). The array analysis revealed that microRNA-885 (miR-885)-5p was the most up-regulated miRNA in the carcinoid tumors with lymphovascular invasion compared with that in those without invasion. In addition, high miR-885-5p expression was independently associated with lymphovascular invasion (P = 0.0002). In conclusion, our findings suggest that miR-885-5p and CIMP status may be useful biomarkers for predicting biological malignancy in patients with rectal carcinoid tumors. C1 [Mitsuhashi, Kei; Yamamoto, Itaru; Kurihara, Hiroyoshi; Kanno, Shinichi; Ito, Miki; Igarashi, Hisayoshi; Ishigami, Keisuke; Sukawa, Yasutaka; Tachibana, Mami; Shinomura, Yasuhisa; Nosho, Katsuhiko] Sapporo Med Univ, Sch Med, Dept Gastroenterol Rheumatol & Clin Immunol, Sapporo, Hokkaido, Japan. [Sukawa, Yasutaka] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sukawa, Yasutaka] Harvard Univ, Sch Med, Boston, MA USA. [Takahashi, Hiroaki] Keiyukai Daini Hosp, Dept Gastroenterol, Sapporo, Hokkaido, Japan. [Tokino, Takashi] Sapporo Med Univ, Sch Med, Dept Med Genome Sci, Res Inst Frontier Med, Sapporo, Hokkaido, Japan. [Maruyama, Reo; Suzuki, Hiromu] Sapporo Med Univ, Sch Med, Dept Mol Biol, Sapporo, Hokkaido, Japan. [Imai, Kohzoh] Univ Tokyo, Inst Med Sci, Tokyo, Japan. [Yamamoto, Hiroyuki] St Marianna Univ, Sch Med, Dept Gastroenterol & Hepatol, Kawasaki, Kanagawa, Japan. RP Nosho, K (reprint author), Sapporo Med Univ, Sch Med, Dept Gastroenterol Rheumatol & Clin Immunol, Sapporo, Hokkaido, Japan. EM nosho@sapmed.ac.jp FU Ono Cancer Research Foundation; Takeda Science Foundation; Sapporo Jikeikai Tomoiki Foundation; Suhara Memorial Foundation; Japanese Society of Gastroenterology Research Foundation FX This work was supported by Ono Cancer Research Foundation (to K.N.), Takeda Science Foundation (to K.N.), Sapporo Jikeikai Tomoiki Foundation (to K.N.), The Suhara Memorial Foundation (to K.N.), and The Japanese Society of Gastroenterology Research Foundation (to K.N.). NR 53 TC 2 Z9 2 U1 2 U2 4 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD SEP 8 PY 2015 VL 6 IS 26 BP 22114 EP 22125 DI 10.18632/oncotarget.4294 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CT6WW UT WOS:000362954800044 PM 26090613 ER PT J AU Ren, Q Peng, M Dong, YL Zhang, YY Chen, M Yin, N Marcantonio, ER Xie, ZC AF Ren, Quan Peng, Mian Dong, Yuanlin Zhang, Yiying Chen, Ming Yin, Ning Marcantonio, Edward R. Xie, Zhongcong TI Surgery plus anesthesia induces loss of attention in mice SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Article DE anesthesia; surgery; attention; synuclein; S100 beta ID NITROUS OXIDE ANESTHESIA; POSTOPERATIVE DELIRIUM; COGNITIVE IMPAIRMENT; ELDERLY-PATIENTS; MEMORY; ISOFLURANE; RATS; INFLAMMATION; ACQUISITION; PATHOLOGY AB There is a need to develop animal models to study postoperative delirium. Inattention is one of the symptoms of delirium. Increases in the levels of alpha-synuclein and S100 beta have been reported to be associated with delirium. Therefore, we set out to determine the effects of surgery plus general anesthesia on the behavioral changes (including loss of attention) in mice and on the levels of alpha-synuclein and S100 beta in the brain tissues of these mice. C57BL/6J mice (2- to 8-months-old) had a simple laparotomy plus isoflurane anesthesia. The behavioral changes, including attention level and the speed of movements, were determined 12, 24, and 48 h after the surgery plus anesthesia in the mice. The levels of alpha-synuclein and S100 beta in the cortex of these mice following the surgery plus anesthesia were determined by Western blot analysis. We found that there was a loss of attention at 24, but not 12 or 48h following the surgery plus anesthesia (49% +/- 5 vs. 33% +/- 2.9, P = 0.011, N = 12) in the mice without significantly affecting the speed of their movements. There were increases in the levels of total alpha-synuclein (139% +/- 33.5 vs. 100% +/- 13.7, P = 0.037, N = 6) and S100(3 (142% +/- 7.7 vs. 100% +/- 6, P = 0.002, N = 6) in the cortex of the mice 12 h following the surgery plus anesthesia. These findings suggested that the surgery plus isoflurane anesthesia might induce behavioral and biochemical/cellular changes associated with delirium. We could use the surgery plus anesthesia in mice to develop an animal model to study postoperative delirium. C1 [Ren, Quan; Yin, Ning] Southeast Univ, Zhonada Hosp, Dept Anesthesia, Nanjing, Jiangsu, Peoples R China. [Ren, Quan; Peng, Mian; Dong, Yuanlin; Zhang, Yiying; Xie, Zhongcong] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, Charlestown, MA 02129 USA. [Ren, Quan; Peng, Mian; Dong, Yuanlin; Zhang, Yiying; Xie, Zhongcong] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Peng, Mian] Wuhan Univ, Zhonanan Hosp, Dept Anesthesia, Wuhan 430072, Peoples R China. [Chen, Ming] Southeast Univ, Zhongda Hosp, Urol Dept, Nanjing, Jiangsu, Peoples R China. [Marcantonio, Edward R.] Beth Israel Deaconess Med Ctr, Dept Med, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Marcantonio, Edward R.] Beth Israel Deaconess Med Ctr, Dept Med, Div Gerontol, Boston, MA 02215 USA. [Marcantonio, Edward R.] Harvard Univ, Sch Med, Boston, MA USA. RP Xie, ZC (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, 149 13th St,Room 4310, Charlestown, MA 02129 USA. EM zxie@mgh.harvard.edu FU National Institutes of Health, Bethesda, Maryland [R21AG038994, R01 GM088801, R01 AG041274]; Investigator-initiated Research grant from Alzheimer's Association, Chicago, Illinois; Cure Alzheimer's Fund, Wellesley, Massachusetts; National Institute on Aging [R01AG030618, P01AG031720]; Mid-Career Investigator Award from the National Institute on Aging [K24AG035075] FX This research was supported by R21AG038994, R01 GM088801, and R01 AG041274 from National Institutes of Health, Bethesda, Maryland, Investigator-initiated Research grant from Alzheimer's Association, Chicago, Illinois, and Cure Alzheimer's Fund, Wellesley, Massachusetts (to ZX). Dr. EM was funded in part by grants R01AG030618, P01AG031720, and a Mid-Career Investigator Award (K24AG035075) from the National Institute on Aging. The costs of isoflurane were generously provided by the Department of Anesthesia, Critical Care and Pain Medicine at Massachusetts General Hospital. The studies were performed in the Geriatric Anesthesia Research Unit in the Department of Anesthesia, Critical Care and Pain Medicine at Massachusetts General Hospital. This manuscript was attributed to the Department of Anesthesia, Critical Care and Pain Medicine at Massachusetts General Hospital and Harvard Medical School, NR 37 TC 2 Z9 2 U1 4 U2 5 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1662-5102 J9 FRONT CELL NEUROSCI JI Front. Cell. Neurosci. PD SEP 8 PY 2015 VL 9 AR 346 DI 10.3389/fncel.2015.00346 PG 8 WC Neurosciences SC Neurosciences & Neurology GA CR4IL UT WOS:000361295300001 PM 26441522 ER PT J AU Schatton, T Yang, J Kleffel, S Uehara, M Barthel, SR Schlapbach, C Zhan, Q Dudeney, S Mueller, H Lee, N de Vries, JC Meier, B Beken, SV Kluth, MA Ganss, C Sharpe, AH Waaga-Gasser, AM Sayegh, MH Abdi, R Scharffetter-Kochanek, K Murphy, GF Kupper, TS Frank, NY Frank, MH AF Schatton, Tobias Yang, Jun Kleffel, Sonja Uehara, Mayuko Barthel, Steven R. Schlapbach, Christoph Zhan, Qian Dudeney, Stephen Mueller, Hansgeorg Lee, Nayoung de Vries, Juliane C. Meier, Barbara Beken, Seppe Vander Kluth, Mark A. Ganss, Christoph Sharpe, Arlene H. Waaga-Gasser, Ana Maria Sayegh, Mohamed H. Abdi, Reza Scharffetter-Kochanek, Karin Murphy, George F. Kupper, Thomas S. Frank, Natasha Y. Frank, Markus H. TI ABCB5 Identifies Immunoregulatory Dermal Cells SO CELL REPORTS LA English DT Article ID MESENCHYMAL STEM-CELLS; REGULATORY T-CELLS; MAINTAIN IMMUNE HOMEOSTASIS; MALIGNANT-MELANOMA; P-GLYCOPROTEIN; IN-VIVO; SKIN; GENERATION; TRANSPLANT; TOLERANCE AB Cell-based strategies represent a new frontier in the treatment of immune-mediated disorders. However, the paucity of markers for isolation of molecularly defined immunomodulatory cell populations poses a barrier to this field. Here, we show that ATP-binding cassette member B5 (ABCB5) identifies dermal immunoregulatory cells (DIRCs) capable of exerting therapeutic immunoregulatory functions through engagement of programmed cell death 1 (PD-1). Purified Abcb5(+) DIRCs suppressed T cell proliferation, evaded immune rejection, homed to recipient immune tissues, and induced Tregs in vivo. In fully major-histocompatibility-complex-mismatched cardiac allotransplantation models, allogeneic DIRCs significantly prolonged allograft survival. Blockade of DIRC-expressed PD-1 reversed the inhibitory effects of DIRCs on T cell activation, inhibited DIRC-dependent Treg induction, and attenuated DIRC-induced prolongation of cardiac allograft survival, indicating that DIRC immunoregulatory function is mediated, at least in part, through PD-1. Our results identify ABCB5(+) DIRCs as a distinct immunoregulatory cell population and suggest promising roles of this expandable cell subset in cellular immunotherapy. C1 [Schatton, Tobias; Kleffel, Sonja; Barthel, Steven R.; Schlapbach, Christoph; Dudeney, Stephen; Mueller, Hansgeorg; Lee, Nayoung; Kupper, Thomas S.; Frank, Markus H.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Schatton, Tobias; Yang, Jun; Uehara, Mayuko; Sayegh, Mohamed H.; Abdi, Reza; Frank, Natasha Y.; Frank, Markus H.] Boston Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA. [Schatton, Tobias; Yang, Jun; Uehara, Mayuko; Sayegh, Mohamed H.; Abdi, Reza; Frank, Natasha Y.; Frank, Markus H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Yang, Jun] Huazhong Univ Sci & Technol, Inst Organ Transplantat, Wuhan 430074, Peoples R China. [Schlapbach, Christoph] Univ Bern, Dept Dermatol, CH-3012 Bern, Switzerland. [Zhan, Qian; Sharpe, Arlene H.; Murphy, George F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [de Vries, Juliane C.; Meier, Barbara; Beken, Seppe Vander; Scharffetter-Kochanek, Karin] Univ Ulm, Dept Dermatol & Allerg Dis, D-89077 Ulm, Germany. [Kluth, Mark A.; Ganss, Christoph] Rheacell GmbH & Co KG, D-69120 Heidelberg, Germany. [Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Sharpe, Arlene H.] Brigham & Womens Hosp, Evergrande Ctr Immunol Dis, Boston, MA 02115 USA. [Waaga-Gasser, Ana Maria] Univ Wurzburg, Sch Med, Dept Surg, D-97080 Wurzburg, Germany. [Frank, Natasha Y.] Boston VA Healthcare Syst, Dept Med, West Roxbury, MA 02132 USA. [Frank, Natasha Y.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Frank, Markus H.] Edith Cowan Univ, Sch Med Sci, Joondalup, WA 6027, Australia. RP Frank, MH (reprint author), Brigham & Womens Hosp, Dept Dermatol, 75 Francis St, Boston, MA 02115 USA. EM markus.frank@childrens.harvard.edu FU NIH/NCI [R01CA113796, R01CA158467, R01CA138231]; Department of Veterans Affairs VA Merit Review Awards [VA BLRD 1I01BX000516, VA RRD 1I01RX000989]; RTG/CEMMA from German Research Foundation (DFG); American Heart Association; Research Career Development Award Dermatology Foundation; Brigham Research Institute; Melanoma International Foundation; NCI SPORE in Skin Cancer Developmental Project Grant; Swiss National Science Foundation; Fondation Rene Touraine; Medical Student Grant from American Skin Association; Rheacell GmbH Co. KG FX This work was supported by NIH/NCI grants R01CA113796, R01CA158467, and R01CA138231 (to M.H.F.), the Department of Veterans Affairs VA Merit Review Awards VA BLR&D 1I01BX000516 and VA RR&D 1I01RX000989 (to N.Y.F.), by a grant RTG/CEMMA from the German Research Foundation (DFG) (to K.S.-K.), a Postdoctoral Fellowship Award from the American Heart Association, a Research Career Development Award from the Dermatology Foundation, and a Fund to Sustain Research Excellence from the Brigham Research Institute (to T.S.). T.S. is the recipient of an Innovative Research Grant from the Melanoma International Foundation and an NCI SPORE in Skin Cancer Developmental Project Grant. C.S. received salary support from the Swiss National Science Foundation, and C.S. and H.M. received salary support from the Fondation Rene Touraine. N.L. is the recipient of a Medical Student Grant from the American Skin Association.; M.H.F. is a co-inventor of the ABCB5-related US patent 6,846,883 (Gene encoding a multidrug resistance human P-glycoprotein homologue on chromosome 7p15-21 and uses thereof) assigned to Brigham and Women's Hospital, Boston, MA, and licensed to Ticeba GmbH (Heidelberg, Germany) and Rheacell GmbH & Co. KG (Heidelberg, Germany). M.H.F. serves as a scientific advisor to Ticeba GmbH and Rheacell GmbH & Co. KG. C.G. is CEO, and M.A.K. is CSO, of Rheacell GmbH & Co. KG. This work was supported in part by a grant from Rheacell GmbH & Co. KG. NR 25 TC 5 Z9 5 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD SEP 8 PY 2015 VL 12 IS 10 BP 1564 EP 1574 DI 10.1016/j.celrep.2015.08.010 PG 11 WC Cell Biology SC Cell Biology GA CQ9WI UT WOS:000360965500006 PM 26321644 ER PT J AU Reddy, VY Dukkipati, SR Neuzil, P Natale, A Albenque, JP Kautzner, J Shah, D Michaud, G Wharton, M Harari, D Mahapatra, S Lambert, H Mansour, M AF Reddy, Vivek Y. Dukkipati, Srinivas R. Neuzil, Petr Natale, Andrea Albenque, Jean-Paul Kautzner, Josef Shah, Dipen Michaud, Gregory Wharton, Marcus Harari, David Mahapatra, Srijoy Lambert, Hendrik Mansour, Moussa TI Randomized, Controlled Trial of the Safety and Effectiveness of a Contact Force-Sensing Irrigated Catheter for Ablation of Paroxysmal Atrial Fibrillation Results of the TactiCath Contact Force Ablation Catheter Study for Atrial Fibrillation (TOCCASTAR) Study SO CIRCULATION LA English DT Article DE ablation techniques; atrial fibrillation; catheter ablation ID ELECTRODE-TISSUE CONTACT; RADIOFREQUENCY LESION SIZE; PULMONARY VEIN ISOLATION; ANTIARRHYTHMIC-DRUGS; 1ST-LINE TREATMENT; WORLDWIDE SURVEY; STEAM POP; FOLLOW-UP; IMPEDANCE; EFFICACY AB Background Contact force (CF) is a major determinant of lesion size and transmurality and has the potential to improve efficacy of atrial fibrillation ablation. This study sought to evaluate the safety and effectiveness of a novel irrigated radiofrequency ablation catheter that measures real-time CF in the treatment of patients with paroxysmal atrial fibrillation. Methods and Results A total of 300 patients with symptomatic, drug-refractory, paroxysmal atrial fibrillation were enrolled in a prospective, multicenter, randomized, controlled trial and randomized to radiofrequency ablation with either a novel CF-sensing catheter or a non-CF catheter (control). The primary effectiveness end point consisted of acute electrical isolation of all pulmonary veins and freedom from recurrent symptomatic atrial arrhythmia off all antiarrhythmic drugs at 12 months. The primary safety end point included device-related serious adverse events. End points were powered to show noninferiority. All pulmonary veins were isolated in both groups. Effectiveness was achieved in 67.8% and 69.4% of subjects in the CF and control arms, respectively (absolute difference, -1.6%; lower limit of 1-sided 95% confidence interval, -10.7%; P=0.0073 for noninferiority). When the CF arm was stratified into optimal CF (90% ablations with 10 g) and nonoptimal CF groups, effectiveness was achieved in 75.9% versus 58.1%, respectively (P=0.018). The primary safety end point occurred in 1.97% and 1.40% of CF patients and control subjects, respectively (absolute difference, 0.57%; upper limit of 1-sided 95% confidence interval, 3.61%; P=0.0004 for noninferiority). Conclusions The CF ablation catheter met the primary safety and effectiveness end points. Additionally, optimal CF was associated with improved effectiveness. Clinical Trial Registration http://www.clinicaltrials.gov. Unique identifier: NCT01278953. C1 [Reddy, Vivek Y.; Dukkipati, Srinivas R.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Neuzil, Petr] Homolka Hosp, Prague, Czech Republic. [Natale, Andrea] Texas Cardiac Arrhythmia Inst, Austin, TX USA. [Albenque, Jean-Paul] Clin Pasteur, Toulouse, France. [Kautzner, Josef] Inst Clin & Expt Med IKEM, Prague, Czech Republic. [Shah, Dipen] Univ Hosp Geneva, Geneva, Switzerland. [Michaud, Gregory] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wharton, Marcus] Med Univ S Carolina, Charleston, SC USA. [Harari, David; Mahapatra, Srijoy; Lambert, Hendrik] St Jude Med Inc, St Paul, MN USA. [Mansour, Moussa] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Reddy, VY (reprint author), Icahn Sch Med Mt Sinai, One Gustave L Levy Pl,Box 1030, New York, NY 10029 USA. EM Vivek.Reddy@mountsinai.org FU St. Jude Medical GVA-Endosense FX This study was supported by a grant from St. Jude Medical GVA-Endosense. NR 21 TC 27 Z9 27 U1 1 U2 4 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 SEP 8 PY 2015 VL 132 IS 10 BP 907 EP 915 DI 10.1161/CIRCULATIONAHA.114.014092 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CR1UJ UT WOS:000361110300003 PM 26260733 ER PT J AU Cavender, MA Steg, PG Smith, SC Eagle, K Ohman, EM Goto, S Kuder, J Im, K Wilson, PWF Bhatt, DL AF Cavender, Matthew A. Steg, Ph Gabriel Smith, Sidney C., Jr. Eagle, Kim Ohman, E. Magnus Goto, Shinya Kuder, Julia Im, Kyungah Wilson, Peter W. F. Bhatt, Deepak L. CA REACH Registry Investigators TI Impact of Diabetes Mellitus on Hospitalization for Heart Failure, Cardiovascular Events, and Death Outcomes at 4 Years From the Reduction of Atherothrombosis for Continued Health (REACH) Registry SO CIRCULATION LA English DT Article DE coronary artery disease; diabetes mellitus; heart failure; registries ID PRIOR MYOCARDIAL-INFARCTION; ACUTE CORONARY SYNDROMES; NONDIABETIC INDIVIDUALS; ARTERY-DISEASE; UNITED-STATES; RISK-FACTORS; RATES; OUTPATIENTS; PREVALENCE; MORTALITY AB Background Despite the known association of diabetes mellitus with cardiovascular events, there are few contemporary data on the long-term outcomes from international cohorts of patients with diabetes mellitus. We sought to describe cardiovascular outcomes at 4 years and to identify predictors of these events in patients with diabetes mellitus. Methods and Results The Reduction of Atherothrombosis for Continued Health (REACH) registry is an international registry of patients at high risk of atherothrombosis or established atherothrombosis. Four-year event rates in patients with diabetes mellitus were determined with the corrected group prognosis method. Of the 45 227 patients in the REACH registry who had follow-up at 4 years, 43.6% (n=19 699) had diabetes mellitus at baseline. The overall risk and hazard ratio (HR) of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke were greater in patients with diabetes compared with patients without diabetes (16.5% versus 13.1%; adjusted HR, 1.27; 95% confidence interval [CI] 1.19-1.35). There was also an increase in both cardiovascular death (8.9% versus 6.0%; adjusted HR, 1.38; 95% CI, 1.26-1.52) and overall death (14.3% versus 9.9%; adjusted HR, 1.40; 95% CI, 1.30-1.51). Diabetes mellitus was associated with a 33% greater risk of hospitalization for heart failure (9.4% versus 5.9%; adjusted odds ratio, 1.33; 95% CI, 1.18-1.50). In patients with diabetes mellitus, heart failure at baseline was independently associated with cardiovascular death (adjusted HR, 2.45; 95% CI, 2.17-2.77; P<0.001) and hospitalization for heart failure (adjusted odds ratio, 4.72; 95% CI, 4.22-5.29; P<0.001). Conclusions Diabetes mellitus substantially increases the risk of death, ischemic events, and heart failure. Patients with both diabetes mellitus and heart failure are at particularly elevated risk of cardiovascular death, highlighting the need for additional therapies in this high-risk population. C1 [Cavender, Matthew A.; Kuder, Julia; Im, Kyungah; Bhatt, Deepak L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Heart & Vasc Ctr, Boston, MA 02115 USA. [Steg, Ph Gabriel] Univ Paris Diderot, Hop Bichat,Alliance Cardiovasc Clin Trials,Dept H, AP HP,Hop Univ Paris Nord Val de Seine,U1148,Fibr, Sorbonne Paris Cite,Lab Vasc Translat Sci,INSERM, Paris, France. [Steg, Ph Gabriel] Univ London Imperial Coll Sci Technol & Med, Natl Heart Lung Inst, Royal Brompton Hosp, London, England. [Smith, Sidney C., Jr.] Univ N Carolina, Chapel Hill, NC USA. [Eagle, Kim] Univ Michigan, Ann Arbor, MI 48109 USA. [Ohman, E. Magnus] Duke Clin Res Inst, Durham, NC USA. [Goto, Shinya] Tokai Univ, Hiratsuka, Kanagawa 25912, Japan. [Wilson, Peter W. F.] Emory Univ, Atlanta, GA 30322 USA. [Wilson, Peter W. F.] Atlanta VA Med Ctr, Atlanta, GA USA. RP Bhatt, DL (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM DLBHATTMD@post.harvard.edu FU Sanofi Aventis; Bristol-Myers Squibb; Waksman Foundation (Tokyo, Japan) FX The REACH registry was sponsored by Sanofi Aventis, Bristol-Myers Squibb, and the Waksman Foundation (Tokyo, Japan) and endorsed by the World Heart Federation. NR 34 TC 17 Z9 17 U1 0 U2 4 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 SEP 8 PY 2015 VL 132 IS 10 BP 923 EP 931 DI 10.1161/CIRCULATIONAHA.114.014796 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CR1UJ UT WOS:000361110300005 PM 26152709 ER PT J AU Rosen, BR Huang, SY Stufflebeam, SM AF Rosen, Bruce R. Huang, Susie Y. Stufflebeam, Steven M. TI Pushing the Limits of Human Neuroimaging SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID CORTEX C1 [Rosen, Bruce R.; Huang, Susie Y.; Stufflebeam, Steven M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rosen, Bruce R.; Huang, Susie Y.; Stufflebeam, Steven M.] Massachusetts Gen Hosp East, Charlestown, MA 02129 USA. RP Rosen, BR (reprint author), Massachusetts Gen Hosp East, NMR Ctr 23011, 149 13th St, Charlestown, MA 02129 USA. EM bruce@nmr.mgh.harvard.edu NR 5 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 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 8 PY 2015 VL 314 IS 10 BP 993 EP 994 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CQ8FA UT WOS:000360840700005 PM 26348745 ER PT J AU Nathan, DM AF Nathan, David M. TI Diabetes Advances in Diagnosis and Treatment SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID BETA-CELL FUNCTION; RANDOMIZED CONTROLLED-TRIAL; IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE INTERVENTION; 10-YEAR FOLLOW-UP; GLYCEMIC CONTROL; INSULIN ANALOGS; INTENSIVE TREATMENT; BLADDER-CANCER; CARDIOVASCULAR OUTCOMES AB IMPORTANCE Chronic diseases have overtaken acute diseases, such as infections, as the major cause of premature mortality worldwide. Diabetes mellitus, a chronic degenerative metabolic disease, has reached epidemic proportions in the past 30 years, with worldwide prevalence approaching 400 million people. OBSERVATIONS AND ADVANCES The epidemic is largely secondary to an increasing sedentary lifestyle and highly prevalent overweight and obesity contributing to the development of type 2 diabetes. Clinical research efforts have developed and demonstrated effective strategies for prevention, and the annual incidence of diabetes in the United States may be decreasing for the first time in 3 decades. The long-term complications of diabetes cause severe morbidity and mortality. Here too the means of reducing the burden of microvascular and cardiovascular disease have been proved. CONCLUSIONS AND RELEVANCE Improved glycemic control and better management of other identified risk factors for the complications of diabetes and more effective treatment of cardiovascular disease and microvascular complications have resulted in a more optimistic outlook for people with diabetes. This review focuses on recent advances in diagnosis and management and the remaining challenges in the prevention and treatment of diabetes mellitus. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Diabet, Boston, MA 02114 USA. RP Nathan, DM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Diabet, 50 Staniford St,Ste 340, Boston, MA 02114 USA. EM dnathan@MGH.Harvard.edu NR 102 TC 53 Z9 55 U1 8 U2 55 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 SEP 8 PY 2015 VL 314 IS 10 BP 1052 EP 1062 DI 10.1001/jama.2015.9536 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA CQ8FA UT WOS:000360840700017 PM 26348754 ER PT J AU Alex, A Li, AR Zeng, XX Tate, RE McKee, ML Capen, DE Zhang, Z Tanzi, RE Zhou, C AF Alex, Aneesh Li, Airong Zeng, Xianxu Tate, Rebecca E. McKee, Mary L. Capen, Diane E. Zhang, Zhan Tanzi, Rudolph E. Zhou, Chao TI A Circadian Clock Gene, Cry, Affects Heart Morphogenesis and Function in Drosophila as Revealed by Optical Coherence Microscopy SO PLOS ONE LA English DT Article ID CARDIAC DYSFUNCTION; TOMOGRAPHY; EXPRESSION; CRYPTOCHROME; DISEASE; RHYTHM; MELANOGASTER; MICE; PHOTORECEPTOR; ENTRAINMENT AB Circadian rhythms are endogenous, entrainable oscillations of physical, mental and behavioural processes in response to local environmental cues such as daylight, which are present in the living beings, including humans. Circadian rhythms have been related to cardiovascular function and pathology. However, the role that circadian clock genes play in heart development and function in a whole animal in vivo are poorly understood. The Drosophila cryptochrome (dCry) is a circadian clock gene that encodes a major component of the circadian clock negative feedback loop. Compared to the embryonic stage, the relative expression levels of dCry showed a significant increase (>100-fold) in Drosophila during the pupa and adult stages. In this study, we utilized an ultrahigh resolution optical coherence microscopy (OCM) system to perform non-invasive and longitudinal analysis of functional and morphological changes in the Drosophila heart throughout its post-embryonic lifecycle for the first time. The Drosophila heart exhibited major morphological and functional alterations during its development. Notably, heart rate (HR) and cardiac activity period (CAP) of Drosophila showed significant variations during the pupa stage, when heart remodeling took place. From the M-mode (2D + time) OCM images, cardiac structural and functional parameters of Drosophila at different developmental stages were quantitatively determined. In order to study the functional role of dCry on Drosophila heart development, we silenced dCry by RNAi in the Drosophila heart and mesoderm, and quantitatively measured heart morphology and function in those flies throughout its development. Silencing of dCry resulted in slower HR, reduced CAP, smaller heart chamber size, pupal lethality and disrupted posterior segmentation that was related to increased expression of a posterior compartment protein, wingless. Collectively, our studies provided novel evidence that the circadian clock gene, dCry, plays an essential role in heart morphogenesis and function. C1 [Alex, Aneesh; Zeng, Xianxu; Zhou, Chao] Lehigh Univ, Dept Elect & Comp Engn, Bethlehem, PA 18015 USA. [Alex, Aneesh; Zeng, Xianxu; Zhou, Chao] Lehigh Univ, Ctr Photon & Nanoelect, Bethlehem, PA 18015 USA. [Li, Airong; Tate, Rebecca E.; Tanzi, Rudolph E.] Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, Boston, MA 02129 USA. [Li, Airong; Tate, Rebecca E.; Tanzi, Rudolph E.] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Zeng, Xianxu; Zhang, Zhan] Zhengzhou Univ, Affiliated Hosp 3, Dept Pathol, Zhengzhou 450000, Henan, Peoples R China. [McKee, Mary L.; Capen, Diane E.] Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02115 USA. [McKee, Mary L.; Capen, Diane E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Zhou, Chao] Lehigh Univ, Bioengn Program, Bethlehem, PA 18015 USA. RP Tanzi, RE (reprint author), Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, Boston, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu; chaozhou@lehigh.edu FU National Institutes of Health [R00EB010071, R15EB019704, R03AR063271, R01AG014713, R01MH060009]; National Science Foundation [1455613]; Cure Alzheimer's Fund; Massachusetts General Hospital ECOR Award; Boston Area Diabetes and Endocrinology Research Centre [DK 57521]; Centre for the Study of Inflammatory Bowel Disease [DK 43351]; Lehigh University Start-up Fund FX This work was supported by the Lehigh University Start-up Fund, National Institutes of Health [R00EB010071 to C.Z., R15EB019704 to C.Z. and A.L., R03AR063271 to A.L., and R01AG014713 and R01MH060009 to R.E. Tanzi], National Science Foundation [1455613 to C.Z. and A. L.], the Cure Alzheimer's Fund [to R.E. Tanzi], and a Massachusetts General Hospital ECOR Award [to A.L.]. The Microscopy Core Facility at the MGH Program in Membrane Biology receives support from the Boston Area Diabetes and Endocrinology Research Centre [DK 57521] and the Centre for the Study of Inflammatory Bowel Disease [DK 43351]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 4 Z9 4 U1 1 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 8 PY 2015 VL 10 IS 9 AR e0137236 DI 10.1371/journal.pone.0137236 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ8YQ UT WOS:000360897600027 PM 26348211 ER PT J AU Dragset, MS Barczak, AK Kannan, N Maerk, M Flo, TH Valla, S Rubin, EJ Steigedal, M AF Dragset, Marte S. Barczak, Amy K. Kannan, Nisha Maerk, Mali Flo, Trude H. Valla, Svein Rubin, Eric J. Steigedal, Magnus TI Benzoic Acid-Inducible Gene Expression in Mycobacteria SO PLOS ONE LA English DT Article ID GRAM-NEGATIVE BACTERIA; META-CLEAVAGE PATHWAY; ESCHERICHIA-COLI; PM PROMOTER; TOL PLASMID; TETRACYCLINE REPRESSORS; TUBERCULOSIS; SMEGMATIS; XYLS; PROTEIN AB Conditional expression is a powerful tool to investigate the role of bacterial genes. Here, we adapt the Pseudomonas putida-derived positively regulated XylS/Pm expression system to control inducible gene expression in Mycobacterium smegmatis and Mycobacterium tuberculosis, the causative agent of human tuberculosis. By making simple changes to a Gram-negative broad-host-range XylS/Pm-regulated gene expression vector, we prove that it is possible to adapt this well-studied expression system to non-Gram-negative species. With the benzoic acid-derived inducer m-toluate, we achieve a robust, time- and dose-dependent reversible induction of Pm-mediated expression in mycobacteria, with low background expression levels. XylS/Pm is thus an important addition to existing mycobacterial expression tools, especially when low basal expression is of particular importance. C1 [Dragset, Marte S.; Rubin, Eric J.; Steigedal, Magnus] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Dragset, Marte S.; Kannan, Nisha; Maerk, Mali; Flo, Trude H.; Steigedal, Magnus] Norwegian Univ Sci & Technol, Ctr Mol Inflammat Res, Dept Canc Res & Mol Med, N-7034 Trondheim, Norway. [Dragset, Marte S.; Valla, Svein] Norwegian Univ Sci & Technol, Dept Biotechnol, N-7034 Trondheim, Norway. [Barczak, Amy K.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Steigedal, Magnus] Cent Norway Reg Hlth Author, Stjordal, Norway. RP Steigedal, M (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 665 Huntington Ave, Boston, MA 02115 USA. EM magnus.steigedal@ntnu.no RI Flo, Trude/E-1311-2013; OI Maerk, Mali/0000-0001-7447-0687; Steigedal, Magnus/0000-0002-3695-3132 FU Research Council of Norway through its Centres of Excellence funding scheme [223255/F50]; Research Council of Norway [220836/F10, 246944/F10]; NTNU; Liaison Committee; Central Norway Regional Health Authority (RHA); Norwegian University of Science and Technology (NTNU) FX This work was partly supported by the Research Council of Norway through its Centres of Excellence funding scheme, project number 223255/F50. In addition the Research Council of Norway supported the work through project numbers 220836/F10 and 246944/F10. In addition NTNU and the Liaison Committee between the Central Norway Regional Health Authority (RHA) and the Norwegian University of Science and Technology (NTNU) contributed with funding to the study. NR 54 TC 0 Z9 0 U1 1 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 8 PY 2015 VL 10 IS 9 AR e0134544 DI 10.1371/journal.pone.0134544 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ8YQ UT WOS:000360897600001 PM 26348349 ER PT J AU Chan, ES Chen, C Cole, GM Wong, BS AF Chan, Elizabeth S. Chen, Christopher Cole, Gregory M. Wong, Boon-Seng TI Differential interaction of Apolipoprotein-E isoforms with insulin receptors modulates brain insulin signaling in mutant human amyloid precursor protein transgenic mice SO SCIENTIFIC REPORTS LA English DT Article ID BETA A-BETA; ALZHEIMERS-DISEASE; TARGETED REPLACEMENT; INTRANASAL INSULIN; COGNITIVE DECLINE; APOE GENOTYPE; MOUSE MODELS; NEURONS; BINDING; CLEARANCE AB It is unclear how human apolipoprotein E4 (ApoE4) increases the risk for Alzheimer's disease (AD). Although A beta levels can lead to insulin signaling impairment, these experiments were done in the absence of human ApoE. To examine ApoE role, we crossed the human ApoE-targeted replacement mice with mutant human amyloid precursor protein (APP) mice. In 26 week old mice with lower A beta levels, the expression and phosphorylation of insulin signaling proteins remained comparable among APP, ApoE3xAPP and ApoE4xAPP mouse brains. When the mice aged to 78 weeks, these proteins were markedly reduced in APP and ApoE4xAPP mouse brains. While A beta can bind to insulin receptor, how ApoE isoforms modulate this interaction remains unknown. Here, we showed that ApoE3 had greater association with insulin receptor as compared to ApoE4, regardless of A beta 42 concentration. In contrast, ApoE4 bound more A beta 42 with increasing peptide levels. Using primary hippocampal neurons, we showed that ApoE3 and ApoE4 neurons are equally sensitive to physiological levels of insulin. However, in the presence of A beta 42, insulin failed to elicit a downstream response only in ApoE4 hippocampal neurons. Taken together, our data show that ApoE genotypes can modulate this A beta-mediated insulin signaling impairment. C1 [Chan, Elizabeth S.; Chen, Christopher; Wong, Boon-Seng] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, Singapore 117595, Singapore. [Chen, Christopher] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Pharmacol, Singapore 117595, Singapore. [Chen, Christopher] NUHS, MACC, Singapore, Singapore. [Cole, Gregory M.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Cole, Gregory M.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Cole, Gregory M.] Vet Affairs Med Ctr, Greater Los Angeles Vet Affairs Healthcare Syst, Geriatr Res & Clin Ctr, Los Angeles, CA USA. RP Wong, BS (reprint author), Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, Singapore 117595, Singapore. EM bswong@nus.edu.sg RI Chen, Christopher/E-7023-2013 FU National University Health System [NUHSRO/2011/005/STB/B2B-01]; Singapore Ministry of Education FX We thank Ms Mei Li Lim, Shiau Chen H'ng and Ket Yin Goh for help in maintaining and genotyping the transgenic mice. This work was supported by a seed grant to BSW from the National University Health System (NUHSRO/2011/005/STB/B2B-01). ESC was supported by a graduate scholarship from Singapore Ministry of Education. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 4 Z9 4 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD SEP 8 PY 2015 VL 5 AR 13842 DI 10.1038/srep13842 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ7PD UT WOS:000360795200002 PM 26346625 ER PT J AU Thukkani, AK Agrawal, K Prince, L Smoot, KJ Dufour, AB Cho, K Gagnon, DR Sokolovskaya, G Ly, S Temiyasathit, S Faxon, DP Gaziano, JM Kinlay, S AF Thukkani, Arun K. Agrawal, Kush Prince, Lillian Smoot, Kyle J. Dufour, Alyssa B. Cho, Kelly Gagnon, David R. Sokolovskaya, Galina Ly, Samantha Temiyasathit, Sara Faxon, David P. Gaziano, J. Michael Kinlay, Scott TI Long-Term Outcomes in Patients With Diabetes Mellitus Related to Prolonging Clopidogrel More Than 12 Months After Coronary Stenting SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE clopidogrel; diabetes mellitus; long-term outcomes; percutaneous coronary interventions ID DUAL-ANTIPLATELET THERAPY; DRUG-ELUTING STENTS; RANDOMIZED CONTROLLED-TRIALS; MYOCARDIAL-INFARCTION; NETWORK METAANALYSIS; IMPLANTATION; DURATION; PLACEMENT; INTERVENTION; MULTICENTER AB BACKGROUND Recent large clinical trials show lower rates of late cardiovascular events by extending clopidogrel >12 months after percutaneous coronary revascularization (PCI). However, concerns of increased bleeding have elicited support for limiting prolonged treatment to high-risk patients. OBJECTIVES The aim of this analysis was to determine the effect of prolonging clopidogrel therapy >12 months versus <= 12 months after PCI on very late outcomes in patients with diabetes mellitus (DM). METHODS Using the Veterans Health Administration, 28,849 patients undergoing PCI between 2002 and 2006 were categorized into 3 groups: 1) 16,332 without DM; 2) 9,905 with DM treated with oral medications or diet; and 3) 2,612 with DM treated with insulin. Clinical outcomes, stratified by stent type, <= 4 years after PCI were determined from the Veterans Health Administration and Medicare databases and risk was assessed by multivariable and propensity score analyses using a landmark analysis starting 1 year after the index PCI. The primary endpoint of the study was the risk of all-cause death or myocardial infarction (MI). RESULTS In patients with DM treated with insulin who received drug-eluting stents (DES), prolonged clopidogrel treatment was associated with a decreased risk of death (hazard ratio [HR]: 0.59; 95% confidence interval [CI]: 0.42 to 0.82) and death or MI (HR: 0.67; 95% CI: 0.49 to 0.92). Similarly, in patients with noninsulin-treated DM receiving DES, prolonged clopidogrel treatment was associated with less death (HR: 0.61; 95% CI: 0.48 to 0.77) and death or MI (HR: 0.61; 95% CI: 0.5 to 0.75). Prolonged clopidogrel treatment was not associated with a lower risk in patients without DM or in any group receiving bare-metal stents. CONCLUSIONS Extending the duration of clopidogrel treatment >12 months may decrease very late death or MI only in patients with DM receiving first-generation DES. Future studies should address this question in patients receiving second-generation DES. (C) 2015 by the American College of Cardiology Foundation. C1 [Thukkani, Arun K.; Agrawal, Kush; Ly, Samantha; Temiyasathit, Sara; Faxon, David P.; Gaziano, J. Michael; Kinlay, Scott] Vet Affairs Boston Healthcare Syst, Div Cardiovasc, Boston, MA USA. [Thukkani, Arun K.; Faxon, David P.; Gaziano, J. Michael; Kinlay, Scott] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Agrawal, Kush] Boston Med Ctr, Div Cardiovasc, Boston, MA USA. [Prince, Lillian; Smoot, Kyle J.; Dufour, Alyssa B.; Cho, Kelly; Gagnon, David R.; Sokolovskaya, Galina; Gaziano, J. Michael] Vet Affairs Boston Healthcare Syst, MAVERIC, Boston, MA USA. [Dufour, Alyssa B.] Hebrew SeniorLife, Inst Aging Res, Boston, MA USA. [Faxon, David P.; Gaziano, J. Michael; Kinlay, Scott] Harvard Univ, Sch Med, Boston, MA USA. RP Kinlay, S (reprint author), VA Boston Healthcare Syst, Div Cardiovasc, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM scott.kinlay@va.gov OI Dufour, Alyssa/0000-0001-8061-9599 FU CSRD VA [I01 CX000440]; Intramural VA [VA999999] NR 25 TC 14 Z9 15 U1 0 U2 5 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 SEP 8 PY 2015 VL 66 IS 10 BP 1091 EP 1101 DI 10.1016/j.jacc.2015.06.1339 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CQ1OR UT WOS:000360367600001 PM 26337986 ER PT J AU Sachdeva, R Allen, J Benavidez, OJ Campbell, RM Douglas, PS Eidem, BW Gold, L Kelleman, MS Lopez, L McCracken, CE Stern, KWD Weiner, RB Welch, E Lai, WW AF Sachdeva, Ritu Allen, Joseph Benavidez, Oscar J. Campbell, Robert M. Douglas, Pamela S. Eidem, Benjamin W. Gold, Lara Kelleman, Michael S. Lopez, Leo McCracken, Courtney E. Stern, Kenan W. D. Weiner, Rory B. Welch, Elizabeth Lai, Wyman W. TI Pediatric Appropriate Use Criteria Implementation Project A Multicenter Outpatient Echocardiography Quality Initiative SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE echocardiography; outpatient; pediatric cardiology ID TRANSTHORACIC ECHOCARDIOGRAPHY; EDUCATIONAL INTERVENTION; CARDIOLOGY; TRANSESOPHAGEAL AB BACKGROUND Recently published appropriate use criteria (AUC) for initial pediatric outpatient transthoracic echocardiography (TTE) have not yet been evaluated for clinical applicability. OBJECTIVES This study sought to determine the appropriateness of TTE as currently performed in pediatric cardiology clinics, diagnostic yield of TTE for various AUC indications, and any gaps in the AUC document. METHODS Data were prospectively collected from patients undergoing initial outpatient TTE in 6 centers. TTE indications (appropriate [A], may be appropriate [M], or rarely appropriate [R]) and findings (normal, incidental, or abnormal) were recorded. RESULTS Of the 2,655 studies ordered by 102 physicians, indications rated A, M, and R were found in 1,876 (71%), 316 (12%), and 319 studies (12%), respectively, and 144 studies (5%) were unclassifiable. Twenty-four of 113 indications (21%) were not used. Innocent murmur and syncope or palpitations with no other indications of cardiovascular disease, a benign family history, and normal electrocardiogram accounted for 75% of indications rated R. Pathologic murmur had the highest yield of abnormal findings (40%). Odds of an abnormal finding in an A or M TTE were 6 times that of R (95% confidence interval [CI]: [2.8 to 12.8]). Abnormal findings were more common in patients <1 year of age than in those >10 years of age (odds ratio: 6.4; 95% CI: 4.7 to 8.7). Age was a significant predictor of an abnormal finding after adjusting for indication and site (p < 0.001). CONCLUSIONS Most TTEs ordered in pediatric cardiology clinics were for indications rated A. AUC ratings successfully stratified indications based on the yield of abnormal findings. This study identified differences in the yield of TTE based on patient age and most common indications rated R. These findings should inform quality improvement efforts and future revisions of the AUC document. (C) 2015 by the American College of Cardiology Foundation. C1 [Sachdeva, Ritu; Campbell, Robert M.; Kelleman, Michael S.; McCracken, Courtney E.] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Sachdeva, Ritu; Campbell, Robert M.; Kelleman, Michael S.; McCracken, Courtney E.] Childrens Healthcare Atlanta, Sibley Heart Ctr Cardiol, Atlanta, GA 30322 USA. [Allen, Joseph; Gold, Lara] Amer Coll Cardiol, Washington, DC USA. [Benavidez, Oscar J.; Weiner, Rory B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Douglas, Pamela S.] Duke Univ, Durham, NC USA. [Eidem, Benjamin W.] Mayo Clin, Rochester, MN USA. [Lopez, Leo; Welch, Elizabeth] Miami Childrens Hosp, Miami, FL USA. [Stern, Kenan W. D.] Childrens Hosp Montefiore, New York, NY USA. [Lai, Wyman W.] Morgan Stanley Childrens Hosp New York Presbyteri, New York, NY USA. RP Sachdeva, R (reprint author), Emory Univ, Sch Med, Childrens Healthcare Atlanta, 1405 Clifton Rd, Atlanta, GA 30322 USA. EM sachdevar@kidsheart.com NR 17 TC 6 Z9 6 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 SEP 8 PY 2015 VL 66 IS 10 BP 1132 EP 1140 DI 10.1016/j.jacc.2015.06.1327 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CQ1OR UT WOS:000360367600007 PM 26337992 ER PT J AU Li, WJ Croce, K Steensma, DP McDermott, DF Ben-Yehuda, O Moslehi, J AF Li, Weijuan Croce, Kevin Steensma, David P. McDermott, David F. Ben-Yehuda, Ori Moslehi, Javid TI Vascular and Metabolic Implications of Novel Targeted Cancer Therapies Focus on Kinase Inhibitors SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review DE cardio-oncology; metabolic toxicity; vascular toxicity ID ENDOTHELIAL GROWTH-FACTOR; CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; RENAL-CELL CARCINOMA; ARTERIAL THROMBOEMBOLIC EVENTS; METASTATIC BREAST-CANCER; CHROMOSOME-POSITIVE LEUKEMIAS; NILOTINIB FORMERLY AMN107; MULTICENTER PHASE-II; OCCLUSIVE DISEASE AB Novel targeted cancer therapies, especially kinase inhibitors, have revolutionized the treatment of many cancers and have dramatically improved the survival of several types of malignancies. Because kinases not only are important in cancer development and progression, but also play a critical role in the cardiovascular (CV) system and metabolic homeostasis, important CV and metabolic sequelae have been associated with several types of kinase inhibitors. This paper reviews the incidences and highlights potential mechanisms of vascular and metabolic perturbations associated with 3 classes of commonly used kinase inhibitors that target the vascular endothelial growth factor signaling pathway, the ABL kinase, and the phosphoinositide 3-kinase/AKT/mammalian target of rapamycin signaling pathway. We propose preventive, screening, monitoring, and management strategies for CV care of patients treated with these novel agents. (C) 2015 by the American College of Cardiology Foundation. C1 [Li, Weijuan] Albert Einstein Coll Med, Jacobi Med Ctr, Dept Med, New York, NY USA. [Croce, Kevin] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Steensma, David P.] Harvard Univ, Harvard Med, Boston, MA USA. [McDermott, David F.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol, Boston, MA 02215 USA. [Ben-Yehuda, Ori] Cardiovasc Res Fdn, New York, NY 10022 USA. [Ben-Yehuda, Ori] Columbia Univ, New York, NY USA. [Moslehi, Javid] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Cardiovasc, Nashville, TN 37232 USA. [Moslehi, Javid] Vanderbilt Univ, Sch Med, Cardiooncol Program, Nashville, TN 37232 USA. RP Ben-Yehuda, O (reprint author), Cardiovasc Res Fdn, Clin Trials Ctr, 111 East 59th St, New York, NY 10022 USA. EM obenyehuda@crf.org; javid.moslehi@vanderbilt.edu RI Li, Weijuan/A-7558-2017 OI Li, Weijuan/0000-0002-3732-1145 NR 126 TC 10 Z9 10 U1 3 U2 13 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 SEP 8 PY 2015 VL 66 IS 10 BP 1160 EP 1178 DI 10.1016/j.jacc.2015.07.025 PG 19 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CQ1OR UT WOS:000360367600011 PM 26337996 ER PT J AU Li, YQ Beckman, KB Caberto, C Kazma, R Lum-Jones, A Haiman, CA Le Marchand, L Stram, DO Saxena, R Cheng, I AF Li, Yuqing Beckman, Kenneth B. Caberto, Christian Kazma, Remi Lum-Jones, Annette Haiman, Christopher A. Le Marchand, Loic Stram, Daniel O. Saxena, Richa Cheng, Iona TI Association of Genes, Pathways, and Haplogroups of the Mitochondrial Genome with the Risk of Colorectal Cancer: The Multiethnic Cohort SO PLOS ONE LA English DT Article ID WIDE ASSOCIATION; DNA; MTDNA; VARIANT; RARE; INSTABILITY; TESTS; CELLS; SCAN; LOOP AB The mitochondrial genome encodes for the synthesis of 13 proteins that are essential for the oxidative phosphorylation (OXPHOS) system. Inherited variation in mitochondrial genes may influence cancer development through changes in mitochondrial proteins, altering the OXPHOS process, and promoting the production of reactive oxidative species. To investigate the role of the OXPHOS pathway and mitochondrial genes in colorectal cancer (CRC) risk, we tested 185 mitochondrial SNPs (mtSNPs), located in 13 genes that comprise four complexes of the OXPHOS pathway and mtSNP groupings for rRNA and tRNA, in 2,453 colorectal cancer cases and 11,930 controls from the Multiethnic Cohort Study. Using the sequence kernel association test, we examined the collective set of 185 mtSNPs, as well as subsets of mtSNPs grouped by mitochondrial pathways, complexes, and genes, adjusting for age, sex, principal components of global ancestry, and self-reported maternal race/ethnicity. We also tested for haplogroup associations using unconditional logistic regression, adjusting for the same covariates. Stratified analyses were conducted by self-reported maternal race/ethnicity. In European Americans, a global test of all genetic variants of the mitochondrial genome identified an association with CRC risk (P = 0.04). In mtSNP-subset analysis, the NADH dehydrogenase 2 (MT-ND2) gene in Complex I was associated with CRC risk at a P-value of 0.001 (q = 0.015). In addition, haplogroup T was associated with CRC risk (OR = 1.66, 95% CI: 1.19-2.33, P = 0.003). No significant mitochondrial pathway and gene associations were observed in the remaining four racial/ethnic groups-African Americans, Asian Americans, Latinos, and Native Hawaiians. In summary, our findings suggest that variations in the mitochondrial genome and particularly in the MT-ND2 gene may play a role in CRC risk among European Americans, but not in other maternal racial/ethnic groups. Further replication is warranted and future studies should evaluate the contribution of mitochondrial proteins encoded by both the nuclear and mitochondrial genomes to CRC risk. C1 [Li, Yuqing; Cheng, Iona] Canc Prevent Inst Calif, Fremont, CA 94538 USA. [Li, Yuqing; Cheng, Iona] Stanford Canc Inst, Palo Alto, CA USA. [Beckman, Kenneth B.] Univ Minnesota, Genom Ctr, Minneapolis, MN USA. [Caberto, Christian; Lum-Jones, Annette; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA. [Kazma, Remi] CEA, Ctr Natl Genotypage, Evry, France. [Kazma, Remi] Novartis Inst BioMed Res, Biomarker Dev, Basel, Switzerland. [Haiman, Christopher A.; Stram, Daniel O.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Saxena, Richa] Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Saxena, Richa] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, England. RP Li, YQ (reprint author), Canc Prevent Inst Calif, Fremont, CA 94538 USA. EM sarahyuqing.li@cpic.org FU NCI [CA140636, CA173782, CA63464, CA54281, CA33619, CA164973, CA98758] FX This work was funded through NCI (CA140636, CA173782, CA63464, CA54281, CA33619, CA164973 and CA98758). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 3 Z9 3 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 4 PY 2015 VL 10 IS 9 AR e0136796 DI 10.1371/journal.pone.0136796 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ6BA UT WOS:000360688200017 PM 26340450 ER PT J AU Korem, T Zeevi, D Suez, J Weinberger, A Avnit-Sagi, T Pompan-Lotan, M Matot, E Jona, G Harmelin, A Cohen, N Sirota-Madi, A Thaiss, CA Pevsner-Fischer, M Sorek, R Xavier, RJ Elinav, E Segal, E AF Korem, Tal Zeevi, David Suez, Jotham Weinberger, Adina Avnit-Sagi, Tali Pompan-Lotan, Maya Matot, Elad Jona, Ghil Harmelin, Alon Cohen, Nadav Sirota-Madi, Alexandra Thaiss, Christoph A. Pevsner-Fischer, Meirav Sorek, Rotem Xavier, Ramnik J. Elinav, Eran Segal, Eran TI MICROBIOME Growth dynamics of gut microbiota in health and disease inferred from single metagenomic samples SO SCIENCE LA English DT Article ID REPLICATION; IDENTIFICATION; CHROMOSOMES; DIVERSITY; BACTERIAL; GENOMES; CANCER; CYCLE AB Metagenomic sequencing increased our understanding of the role of the microbiome in health and disease, yet it only provides a snapshot of a highly dynamic ecosystem. Here, we show that the pattern of metagenomic sequencing read coverage for different microbial genomes contains a single trough and a single peak, the latter coinciding with the bacterial origin of replication. Furthermore, the ratio of sequencing coverage between the peak and trough provides a quantitative measure of a species' growth rate. We demonstrate this in vitro and in vivo, under different growth conditions, and in complex bacterial communities. For several bacterial species, peak-to-trough coverage ratios, but not relative abundances, correlated with the manifestation of inflammatory bowel disease and type II diabetes. C1 [Korem, Tal; Zeevi, David; Weinberger, Adina; Avnit-Sagi, Tali; Pompan-Lotan, Maya; Matot, Elad; Cohen, Nadav; Segal, Eran] Weizmann Inst Sci, Dept Appl Math & Comp Sci, IL-76100 Rehovot, Israel. [Korem, Tal; Zeevi, David; Weinberger, Adina; Avnit-Sagi, Tali; Pompan-Lotan, Maya; Matot, Elad; Cohen, Nadav; Segal, Eran] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. [Suez, Jotham; Thaiss, Christoph A.; Pevsner-Fischer, Meirav; Elinav, Eran] Weizmann Inst Sci, Immunol Dept, IL-76100 Rehovot, Israel. [Jona, Ghil] Weizmann Inst Sci, Dept Biol Serv, IL-76100 Rehovot, Israel. [Harmelin, Alon] Weizmann Inst Sci, Dept Vet Resources, IL-76100 Rehovot, Israel. [Sirota-Madi, Alexandra; Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Cambridge, MA 02138 USA. [Sirota-Madi, Alexandra; Xavier, Ramnik J.] Broad Inst, Cambridge, MA USA. [Sorek, Rotem] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel. RP Elinav, E (reprint author), Weizmann Inst Sci, Immunol Dept, IL-76100 Rehovot, Israel. EM eran.elinav@weizmann.ac.il; eran.segal@weizmann.ac.il FU Ministry of Science, Technology, and Space, Israel; Strauss Institute fellowship for nutritional research; Boehringer Ingelheim Fonds Ph.D. Fellowship; Leona M. and Harry B. Helmsley Charitable Trust; Gurwin Family Fund for Scientific Research; Crown Endowment Fund for Immunological Research; Benoziyo Endowment Fund for the Advancement of Science; Adelis Foundation; CNRS (Centre National de la Recherche Scientifique); European Research Council; German-Israel Binational foundation; Israel Science Foundation (ISF); Minerva Foundation; Rising Tide foundation; European Research Council (ERC); ISF; estate of Jack Gitlitz; estate of Lydia Hershkovich; estate of Samuel and Alwyn J. Weber FX We thank the members of the Segal and Elinav laboratories for fruitful discussions. T.K. and D.Z. are supported by the Ministry of Science, Technology, and Space, Israel. T.K. is the recipient of the Strauss Institute fellowship for nutritional research. C.A.T. is the recipient of a Boehringer Ingelheim Fonds Ph.D. Fellowship. E.E. is supported by Yael and Rami Ungar, Israel; Leona M. and Harry B. Helmsley Charitable Trust; the Gurwin Family Fund for Scientific Research; Crown Endowment Fund for Immunological Research; estate of Jack Gitlitz; estate of Lydia Hershkovich; the Benoziyo Endowment Fund for the Advancement of Science; Adelis Foundation; John L. and Vera Schwartz, Pacific Palisades; Alan Markovitz, Canada; Cynthia Adelson, Canada; CNRS (Centre National de la Recherche Scientifique); estate of Samuel and Alwyn J. Weber; Mr. and Mrs. Donald L. Schwarz, Sherman Oaks; grants funded by the European Research Council; the German-Israel Binational foundation; the Israel Science Foundation (ISF); the Minerva Foundation; and the Rising Tide foundation. E.E. is the incumbent of the Rina Gudinski Career Development Chair. This work was supported by grants from the European Research Council (ERC) and the ISF to E.S. The European Nucleotide Archive (ENA) accession number for the microbial shotgun sequences is PRJEB9718. The pipeline tool will be made publicly available at http://genie.weizmann.ac.il/software/bac_growth.html. All human studies were approved by the Tel Aviv Sourasky Medical Center Institutional Review Board, approval numbers TLV-0658-12, TLV-0050-13, and TLV-0522-10, and the Weizmann Institute of Science Bioethics and Embryonic Stem Cell Research oversight (ESCRO) committee. The trial was reported to https://clinicaltrials.gov, identifier NCT01892956. The study did not necessitate or involve randomization. Author contributions: T.K. and D.Z. conceived the project, designed and conducted the analyses, interpreted the results, and wrote the manuscript. J.S. devised and performed all experiments in mice, anaerobic, and pathogenic bacteria. A.W. directed some of the experiments and the production of libraries and sequencing from samples collected in this study and provided critical insights to the manuscript. T.K., D.Z., J.S., and A.W. equally contributed to this work. T.A.-S., M. P.-L., and E.M. performed experiments and extraction and sequencing of samples. M.P.-F. performed experiments. G.J. performed chemostat experiments. A.H. supervised germ-free mouse experiments. N.C. aided in the design of the computational pipeline and in conducting the analyses. A. S.-M. and R.J.X. directed the PRISM cohort. C.A.T. and E.E. directed the circadian experiments. R.S. and E.S. directed the dietary intervention study. E.E. and E.S. conceived and directed the project and analyses, designed experiments, interpreted the results, and wrote the manuscript. NR 26 TC 29 Z9 32 U1 12 U2 85 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 SEP 4 PY 2015 VL 349 IS 6252 BP 1101 EP 1106 DI 10.1126/science.aac4812 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ5FO UT WOS:000360628900042 PM 26229116 ER PT J AU Herrera, BS Kantarci, A Zarrough, A Hasturk, H Leung, KP Van Dyke, TE AF Herrera, Bruno S. Kantarci, Alpdogan Zarrough, Ahmed Hasturk, Hatice Leung, Kai P. Van Dyke, Thomas E. TI LXA(4) actions direct fibroblast function and wound closure SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Docosahexaenoic acids; Lipoxins; Resolvin D2; Inflammation; Wound healing; Collagen ID PRORESOLVING LIPID MEDIATORS; RESOLVIN E1; AIRWAY INFLAMMATION; IN-VIVO; RESOLUTION; MODEL; MECHANISMS; PERIODONTITIS; REGENERATION; PROTECTS AB Timely resolution of inflammation is crucial for normal wound healing. Resolution of inflammation is an active biological process regulated by specialized lipid mediators including the lipoxins and resolvins. Failure of resolution activity has a major negative impact on wound healing in chronic inflammatory diseases that is manifest as excess fibrosis and scarring. Lipoxins, including Lipoxin A(4) (LXA(4)), have known anti-fibrotic and anti-scarring properties. The goal of this study was to elucidate the impact of LXA(4) on fibroblast function. Mouse fibroblasts (3T3 Mus musculus Swiss) were cultured for 72 h in the presence of TGF-beta 1, to induce fibroblast activation. The impact of exogenous TGF-beta 1 (1 ng/mL) on LXA(4) receptor expression (ALX/FPR2) was determined by flow cytometry. Fibroblast proliferation was measured by bromodeoxyuridine (BrdU) labeling and migration in a "scratch" assay wound model. Expression of alpha-smooth muscle actin (alpha-SMA), and collagen types I and III were measured by Western blot. We observed that TGF-beta 1 up-regulates LXA(4) receptor expression, enhances fibroblast proliferation, migration and scratch wound closure. alpha-SMA levels and Collagen type I and III deposition were also enhanced. LXA(4) slowed fibroblast migration and scratch wound closure at early time points (24 h), but wound closure was equal to TGF-beta 1 alone at 48 and 72 h. LXA(4) tended to slow fibroblast proliferation at both concentrations, but had no impact on alpha-SMA or collagen production by TGF-beta 1 stimulated fibroblasts. The generalizability of the actions of resolution molecules was examined in experiments repeated with resolvin D2 (RvD2) as the agonist The activity of RvD2 mimicked the actions of LXA(4) in all assays, through an as yet unidentified receptor. The results suggest that mediators of resolution of inflammation enhance wound healing and limit fibrosis in part by modulating fibroblast function. (C) 2015 Elsevier Inc. All rights reserved. C1 [Herrera, Bruno S.; Kantarci, Alpdogan; Zarrough, Ahmed; Hasturk, Hatice; Van Dyke, Thomas E.] Forsyth Inst, Dept Appl Oral Sci, Ctr Periodontol, Cambridge, MA 02142 USA. [Herrera, Bruno S.; Leung, Kai P.] US Army Dent & Trauma Res Detachment, Inst Surg Res, Microbiol Branch, Jbsa Ft Sam Houston, TX USA. RP Van Dyke, TE (reprint author), Forsyth Inst, Dept Appl Oral Sci, Ctr Periodontol, Cambridge, MA 02142 USA. EM kai.p.leung.civ@mail.mil; tvandyke@forsyth.org FU US Army Medical Research and Material Command Combat Casualty Care (RAD II) Directorate; Clinical Rehabilitative Medicine (RAD V) Research Directorate; National Institute of Dental and Craniofacial Research [DE15566, DE19938]; National Research Council Research Associateship Award at U.S. Army Institute of Surgical Research FX This work was supported in part by the US Army Medical Research and Material Command Combat Casualty Care (RAD II), Clinical Rehabilitative Medicine (RAD V) Research Directorates and the National Institute of Dental and Craniofacial Research grants DE15566 and DE19938. This research was performed while the first author held a National Research Council Research Associateship Award at U.S. Army Institute of Surgical Research. NR 37 TC 2 Z9 3 U1 2 U2 8 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 SEP 4 PY 2015 VL 464 IS 4 BP 1072 EP 1077 DI 10.1016/j.bbrc.2015.07.076 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA CP4UJ UT WOS:000359877800017 PM 26188508 ER PT J AU Horn, KP Yap, JT Agarwal, N Morton, KA Kadrmas, DJ Beardmore, B Butterfield, RI Boucher, K Hoffman, JM AF Horn, Kevin P. Yap, Jeffrey T. Agarwal, Neeraj Morton, Kathryn A. Kadrmas, Dan J. Beardmore, Britney Butterfield, Regan I. Boucher, Kenneth Hoffman, John M. TI FDG and FLT-PET for Early measurement of response to 37.5 mg daily sunitinib therapy in metastatic renal cell carcinoma SO CANCER IMAGING LA English DT Article DE F-18-fluorodeoxyglucose (FDG); F-18-fluorothymidine (FLT); Positron emission tomography (PET); Renal cell carcinoma; Response assessment; Sunitinib; Tumor metabolism; Tumor proliferation ID POSITRON-EMISSION-TOMOGRAPHY; TYROSINE KINASE INHIBITOR; ENDOTHELIAL GROWTH-FACTOR; IN-VIVO; DISTANT METASTASES; ANTITUMOR-ACTIVITY; SOLID TUMORS; CANCER; SU11248; PROLIFERATION AB Background: Metastatic renal cell carcinoma has a poor prognosis and an intrinsic resistance to standard treatment. Sunitinib is an oral receptor tyrosine kinase inhibitor that has been used as a first-line targeted therapy in metastatic renal cell carcinoma. While computed tomography (CT) is currently the gold standard for response assessment in oncological trials, numerous studies have shown that positron emission tomography (PET) imaging can provide information predictive of tumor response to treatment earlier than the typical interval for standard of care follow-up CT imaging. In this exploratory study we sought to characterize early tumor response in patients with metastatic renal cell carcinoma treated with continuous daily 37.5 mg sunitinib therapy. Methods: Twenty patients underwent dynamic acquisition positron emission tomography (PET) imaging using F-18-fluorodeoxyglucose (FDG) and F-18-fluorothymidine (FLT) at baseline and early in treatment (after 1, 2, 3 or 4 weeks) with 37.5 mg continuous daily dosing of sunitinib. Semi-quantitative analyses were performed to characterize the tumor metabolic (FDG) and proliferative (FLT) responses to treatment. Results: Proliferative responses were observed in 9/19 patients and occurred in 2 patients at one week (the earliest interval evaluated) after the initiation of therapy. A metabolic response was observed in 5/19 patients, however this was not observed until after two weeks of therapy were completed. Metabolic progression was observed in 2/19 patients and proliferative progression was observed in 1/19 patients. Baseline FDG-PET tumor maximum standardized uptake values correlated inversely with overall survival (p = 0.0036). Conversely, baseline F-18-fluorothymidine PET imaging did not have prognostic value (p = 0.56) but showed a greater early response rate at 1-2 weeks after initiating therapy. Conclusions: While preliminary in nature, these results show an immediate and sustained proliferative response followed by a delayed metabolic response beginning after two weeks in metastatic renal cell carcinoma treated with a continuous daily dose of 37.5 mg sunitinib. The results provide evidence of tumor response to lower-dose sunitinib while also supporting the inclusion of PET imaging as a tool for early assessment in oncological clinical trials. C1 [Horn, Kevin P.; Yap, Jeffrey T.; Morton, Kathryn A.; Kadrmas, Dan J.; Beardmore, Britney; Hoffman, John M.] Univ Utah, Huntsman Canc Inst, Ctr Quantitat Canc Imaging, Salt Lake City, UT 84112 USA. [Horn, Kevin P.; Yap, Jeffrey T.; Morton, Kathryn A.; Kadrmas, Dan J.; Hoffman, John M.] Univ Utah, Dept Radiol, Salt Lake City, UT 84132 USA. [Agarwal, Neeraj] Univ Utah, Huntsman Canc Inst, Dept Med, Salt Lake City, UT 84112 USA. [Butterfield, Regan I.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Boucher, Kenneth] Univ Utah, Huntsman Canc Inst, Dept Internal Med, Salt Lake City, UT 84112 USA. RP Yap, JT (reprint author), Univ Utah, Huntsman Canc Inst, Ctr Quantitat Canc Imaging, 1950 Circle Hope Dr,Suite 6810, Salt Lake City, UT 84112 USA. EM jeffrey.yap@hci.utah.edu FU National Comprehensive Cancer Network Oncology Research Program (Pfizer, Inc.); Center for Quantitative Cancer Imaging at the Huntsman Cancer Institute; Cancer Center Support Grant from the NCI/NIH [3P30CA042014]; Huntsman Cancer Foundation FX This project was funded by a grant from the National Comprehensive Cancer Network Oncology Research Program (with general research support provided by Pfizer, Inc.) and the Center for Quantitative Cancer Imaging at the Huntsman Cancer Institute. The project was also facilitated by a Cancer Center Support Grant from the NCI/NIH (3P30CA042014) and by the Huntsman Cancer Foundation. NR 39 TC 6 Z9 6 U1 0 U2 2 PU E-MED PI LONDON PA PO BOX 29761, LONDON, NW3 7ZS, ENGLAND SN 1470-7330 EI 1740-5025 J9 CANCER IMAGING JI Cancer Imaging PD SEP 3 PY 2015 VL 15 AR 15 DI 10.1186/s40644-015-0049-x PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DA0ZJ UT WOS:000367525800002 PM 26335224 ER PT J AU Hosios, AM Fiske, BP Gui, DY Vander Heiden, MG AF Hosios, Aaron M. Fiske, Brian P. Gui, Dan Y. Vander Heiden, Matthew G. TI Lack of Evidence for PKM2 Protein Kinase Activity SO MOLECULAR CELL LA English DT Article ID PYRUVATE-KINASE; GENE-TRANSCRIPTION; CELL-PROLIFERATION; CANCER-CELLS; TUMOR-CELLS; M2; PHOSPHORYLATION; ISOFORM; PROMOTES; SERINE AB The role of pyruvate kinase M2 (PKM2) in cell proliferation is controversial. A unique function of PKM2 proposed to be important for the proliferation of some cancer cells involves the direct activity of this enzyme as a protein kinase; however, a detailed biochemical characterization of this activity is lacking. Using [P-32]-phosphoenolpyruvate (PEP) we examine the direct substrates of PKM2 using recombinant enzyme and in vitro systems where PKM2 is genetically deleted. Labeling of some protein species from [P-32]-PEP can be observed; however, most were dependent on the presence of ADP, and none were dependent on the presence of PKM2. In addition, we also failed to observe PKM2-dependent transfer of phosphate from ATP directly to protein. These findings argue against a role for PKM2 as a protein kinase. C1 [Hosios, Aaron M.; Fiske, Brian P.; Gui, Dan Y.; Vander Heiden, Matthew G.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Vander Heiden, Matthew G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Vander Heiden, MG (reprint author), MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. EM mvh@mit.edu FU HHMI; Vertex Scholars Program; Koch Institute; NCI [R01CA168653, P30CA14051]; Burroughs Wellcome Fund; [T32GM007287] FX U87 and U87 EGFR-VIII cells were generously provided by the White Lab at MIT. We acknowledge support from the HHMI International Student Research Fellowship, the Vertex Scholars Program, T32GM007287, and Koch Institute Graduate Student Fellowships, as well as funding from the NCI (R01CA168653, P30CA14051) and the Burroughs Wellcome Fund. NR 28 TC 18 Z9 18 U1 1 U2 8 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 SEP 3 PY 2015 VL 59 IS 5 BP 850 EP 857 DI 10.1016/j.molcel.2015.07.013 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CW7GM UT WOS:000365166100014 PM 26300261 ER PT J AU Elia, AEH Boardman, AP Wang, DC Huttlin, EL Everley, RA Dephoure, N Zhou, CS Koren, I Gygi, SP Elledge, SJ AF Elia, Andrew E. H. Boardman, Alexander P. Wang, David C. Huttlin, Edward L. Everley, Robert A. Dephoure, Noah Zhou, Chunshui Koren, Itay Gygi, Steven P. Elledge, Stephen J. TI Quantitative Proteomic Atlas of Ubiquitination and Acetylation in the DNA Damage Response SO MOLECULAR CELL LA English DT Article ID DOUBLE-STRAND BREAKS; REPLICATION FORKS; GENOME STABILITY; CYCLIN-F; PROTEIN; CHROMATIN; DYNAMICS; PATHWAY; LIGASE; ATM AB Execution of the DNA damage response (DDR) relies upon a dynamic array of protein modifications. Using quantitative proteomics, we have globally profiled ubiquitination, acetylation, and phosphorylation in response to UV and ionizing radiation. To improve acetylation site profiling, we developed the strategy FACET-IP. Our datasets of 33,500 ubiquitination and 16,740 acetylation sites provide valuable insight into DDR remodeling of the proteome. We find that K6-and K33-linked polyubiquitination undergo bulk increases in response to DNA damage, raising the possibility that these linkages are largely dedicated to DDR function. We also show that Cullin-RING ligases mediate 10% of DNA damage-induced ubiquitination events and that EXO1 is an SCF-Cyclin F substrate in the response to UV radiation. Our extensive datasets uncover additional regulated sites on known DDR players such as PCNA and identify previously unknown DDR targets such as CENPs, underscoring the broad impact of the DDR on cellular physiology. C1 [Elia, Andrew E. H.; Boardman, Alexander P.; Wang, David C.; Zhou, Chunshui; Koren, Itay; Elledge, Stephen J.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Elia, Andrew E. H.; Boardman, Alexander P.; Wang, David C.; Zhou, Chunshui; Koren, Itay; Elledge, Stephen J.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Elia, Andrew E. H.; Boardman, Alexander P.; Wang, David C.; Zhou, Chunshui; Koren, Itay; Elledge, Stephen J.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Elia, Andrew E. H.; Boardman, Alexander P.; Wang, David C.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Huttlin, Edward L.; Everley, Robert A.; Dephoure, Noah; Gygi, Steven P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Elledge, SJ (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. EM selledge@genetics.med.harvard.edu RI Dephoure, Noah/N-7818-2014 OI Dephoure, Noah/0000-0001-5802-2657 FU Burroughs Wellcome Fund CAMS Award; K12 Paul Calabresi Award for Oncology; NIH [GM44664, GM67945] FX We thank members of the Elledge and Gygi labs for helpful discussions. We also thank W. Harper for the Cul3 and Cul4 dominant-negative clones. A.E.H.E is supported by a Burroughs Wellcome Fund CAMS Award and K12 Paul Calabresi Award for Oncology. This work was supported by NIH grants to S.J.E. (GM44664) and S.P.G. (GM67945). S.J.E. is an Investigator with the Howard Hughes Medical Institute. NR 54 TC 28 Z9 29 U1 2 U2 19 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 SEP 3 PY 2015 VL 59 IS 5 BP 867 EP 881 DI 10.1016/j.molcel.2015.05.006 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CW7GM UT WOS:000365166100016 PM 26051181 ER PT J AU Brazin, KN Mallis, RJ Das, DK Feng, YN Hwang, W Wang, JH Wagner, G Lang, MJ Reinherz, EL AF Brazin, Kristine N. Mallis, Robert J. Das, Dibyendu Kumar Feng, Yinnian Hwang, Wonmuk Wang, Jia-huai Wagner, Gerhard Lang, Matthew J. Reinherz, Ellis L. TI Structural features of the alpha beta TCR mechanotransduction apparatus that promote pMHC discrimination SO FRONTIERS IN IMMUNOLOGY LA English DT Review DE T cell receptor; antigen recognition; mechanosensor; catch bond; kinetic proofreading; pre-TCR; thymic development; CD3 ID CELL RECEPTOR-CD3 COMPLEX; ANTIGEN RECEPTOR; T-CELLS; CRYSTAL-STRUCTURE; FG LOOP; CD3-EPSILON-GAMMA HETERODIMER; THYMOCYTE DEVELOPMENT; STEPWISE EVOLUTION; ANTIBODY FRAGMENT; CYTOPLASMIC TAIL AB The alpha beta TCR was recently revealed to function as a mechanoreceptor. That is, it leverages mechanical energy generated during immune surveillance and at the immunological synapse to drive biochemical signaling following ligation by a specific foreign peptide MHC complex (pMHC). Here, we review the structural features that optimize this transmembrane (TM) receptor for mechanotransduction. Specialized adaptations include (1) the CpFG loop region positioned between V beta and C beta domains that allosterically gates both dynamic T cell receptor (TCR) pMHC bond formation and lifetime; (2) the rigid super p-sheet amalgams of heterodimeric CD3 epsilon gamma and CD3 epsilon delta ectodomain components of the alpha beta TCR complex; (3) the alpha beta TCR subunit connecting peptides linking the extracellular and TM segments, particularly the oxidized CxxC motif in each CD3 heterodimeric subunit that facilitates force transfer through the TM segments and surrounding lipid, impacting cytoplasmic tail conformation; and (4) quaternary changes in the alpha beta TCR complex that accompany pMHC ligation under load. How bioforces foster specific alpha beta TCR-based pMHC discrimination and why dynamic bond formation is a primary basis for kinetic proofreading are discussed. We suggest that the details of the molecular rearrangements of individual alpha beta TCR subunit components can be analyzed utilizing a combination of structural biology, single-molecule FRET, optical tweezers, and nanobiology, guided by insightful atomistic molecular dynamic studies. Finally, we review very recent data showing that the pre-TCR complex employs a similar mechanobiology to that of the alpha beta TCR to interact with self-pMHC ligands, impacting early thymic repertoire selection prior to the CD4(+)CD8(+) double positive thymocyte stage of development. C1 [Brazin, Kristine N.; Wang, Jia-huai; Reinherz, Ellis L.] Dana Farber Canc Inst, Immunobiol Lab, Dept Med Oncol, Boston, MA 02115 USA. [Brazin, Kristine N.; Wang, Jia-huai; Reinherz, Ellis L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Mallis, Robert J.; Wagner, Gerhard] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Das, Dibyendu Kumar; Feng, Yinnian; Lang, Matthew J.] Vanderbilt Univ, Dept Chem & Biomol Engn, Nashville, TN 37235 USA. [Hwang, Wonmuk] Texas A&M Univ, Dept Biomed Engn, College Stn, TX USA. [Hwang, Wonmuk] Texas A&M Univ, Dept Mat Sci & Engn, College Stn, TX USA. [Hwang, Wonmuk] Korea Inst Adv Study, Sch Computat Sci, Seoul, South Korea. [Wang, Jia-huai] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Lang, Matthew J.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. RP Reinherz, EL (reprint author), Dana Farber Canc Inst, Immunobiol Lab, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM ellis_reinherz@dfci.harvard.edu FU NIH [RO1 AI 100643, AI037581, PO1 GM047467] FX This work is supported by NIH grants RO1 AI 100643, AI037581 and PO1 GM047467 and a Farrah Fawcett Foundation/Stand Up to Cancer Award. DKD is a George Russell Chambers postdoctoral fellow. Note that Figures 2A, 5, and 6A were adapted from Das et al. (PNAS 2015; 112:1517), NR 78 TC 6 Z9 6 U1 2 U2 11 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PD SEP 3 PY 2015 VL 6 BP 1 EP 13 AR 441 DI 10.3389/fimmu.2015.00441 PG 13 WC Immunology SC Immunology GA CR4RB UT WOS:000361323500001 PM 26388869 ER PT J AU Lee, JM Kim, KH Shin, A Chao, MJ Abu Elneel, K Gillis, T Mysore, JS Kaye, JA Zahed, H Kratter, IH Daub, AC Finkbeiner, S Li, H Roach, JC Goodman, N Hood, L Myers, RH MacDonald, ME Gusella, JF AF Lee, Jong-Min Kim, Kyung-Hee Shin, Aram Chao, Michael J. Abu Elneel, Kawther Gillis, Tammy Mysore, Jayalakshmi Srinidhi Kaye, Julia A. Zahed, Hengameh Kratter, Ian H. Daub, Aaron C. Finkbeiner, Steven Li, Hong Roach, Jared C. Goodman, Nathan Hood, Leroy Myers, Richard H. MacDonald, Marcy E. Gusella, James F. TI Sequence-Level Analysis of the Major European Huntington Disease Haplotype SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID ANTISENSE OLIGONUCLEOTIDES; REPEAT INSTABILITY; PREDICT-HD; LENGTH; EXPANSION; ASSOCIATION; MOUSE; ONSET; AGE AB Huntington disease (HD) reflects the dominant consequences of a CAG-repeat expansion in HIT. Analysis of common SNP-based haplotypes has revealed that most European HD subjects have distinguishable HTT haplotypes on their normal and disease chromosomes and that -50% of the latter share the same major HD haplotype. We reasoned that sequence-level investigation of this founder haplotype could provide significant insights into the history of HD and valuable information for gene-targeting approaches. Consequently, we performed whole-genome sequencing of HD and control subjects from four independent families in whom the major European HD haplotype segregates with the disease. Analysis of the full-sequence-based HTT haplotype indicated that these four families share a common ancestor sufficiently distant to have permitted the accumulation of family-specific variants. Confirmation of new CAG-expansion mutations on this haplotype suggests that unlike most founders of human disease, the common ancestor of HD-affected families with the major haplotype most likely did not have HD. Further, availability of the full sequence data validated the use of SNP imputation to predict the optimal variants for capturing heterozygosity in personalized allele-specific gene-silencing approaches. As few as ten SNPs are capable of revealing heterozygosity in more than 97% of European HD subjects. Extension of allele-specific silencing strategies to the few remaining homozygous individuals is likely to be achievable through additional known SNPs and discovery of private variants by complete sequencing of HIT. These data suggest that the current development of gene-based targeting for HD could be extended to personalized allele-specific approaches in essentially all HD individuals of European ancestry. C1 [Lee, Jong-Min; Kim, Kyung-Hee; Shin, Aram; Chao, Michael J.; Abu Elneel, Kawther; Gillis, Tammy; Mysore, Jayalakshmi Srinidhi; MacDonald, Marcy E.; Gusella, James F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Lee, Jong-Min; MacDonald, Marcy E.; Gusella, James F.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Lee, Jong-Min; Kim, Kyung-Hee; Chao, Michael J.; MacDonald, Marcy E.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Kaye, Julia A.; Zahed, Hengameh; Kratter, Ian H.; Daub, Aaron C.; Finkbeiner, Steven] Univ Calif San Francisco, Gladstone Inst Neurol Dis, San Francisco, CA 94158 USA. [Li, Hong; Roach, Jared C.; Goodman, Nathan; Hood, Leroy] Inst Syst Biol, Seattle, WA 98109 USA. [Myers, Richard H.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Gusella, James F.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Lee, JM (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM jlee51@mgh.harvard.edu FU National Institute of Neurological Disorders and Stroke ("Huntington's Disease Center Without Walls") [P50NS016367, U01NS082079, R01NS091161]; Center for Systems Biology P50 (NIH) [GM076547]; University of Luxembourg Institute for Systems Biology Program; Huntington's Disease Society of America's Coalition for the Cure; Taube/Koret Center for Neurodegenerative Diseases; Gladstone Institutes; NIH [X01 HG007750] FX We thank the Huntington-disease-affected families who contributed their time and blood samples to make this work possible. Support was provided by grants from the National Institute of Neurological Disorders and Stroke ("Huntington's Disease Center Without Walls," P50NS016367, U01NS082079, R01NS091161), the Center for Systems Biology P50 (GM076547, NIH), the University of Luxembourg Institute for Systems Biology Program, and the Huntington's Disease Society of America's Coalition for the Cure. Additional support came from the Taube/Koret Center for Neurodegenerative Diseases (S.F.), the Gladstone Institutes (S.F.), and a grant from the NIH (X01 HG007750 to S.F.). NR 26 TC 2 Z9 2 U1 1 U2 8 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 SEP 3 PY 2015 VL 97 IS 3 BP 435 EP 444 DI 10.1016/j.ajhg.2015.07.017 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA CR1KW UT WOS:000361084700006 PM 26320893 ER PT J AU Labbe, DP Zadra, G Ebot, EM Mucci, LA Kantoff, PW Loda, M Brown, M AF Labbe, D. P. Zadra, G. Ebot, E. M. Mucci, L. A. Kantoff, P. W. Loda, M. Brown, M. TI Role of diet in prostate cancer: the epigenetic link SO ONCOGENE LA English DT Review ID GROWTH-FACTOR-I; PROTEIN LYSINE ACETYLATION; TUMOR-SUPPRESSOR GENES; HISTONE ACETYLATION; DNA HYPOMETHYLATION; CELLULAR-METABOLISM; METHYLATION STATUS; TRANSGENIC MOUSE; ENERGY-BALANCE; TRAMP MICE AB Diet is hypothesized to be a critical environmentally related risk factor for prostate cancer (PCa) development, and specific diets and dietary components can also affect PCa progression; however, the mechanisms underlying these associations remain elusive. As for a maturing organism, PCa's epigenome is plastic and evolves from the pre-neoplastic to the metastatic stage. In particular, epigenetic remodeling relies on substrates or cofactors obtained from the diet. Here we review the evidence that bridges dietary modulation to alterations in the prostate epigenome. We propose that such diet-related effects offer a mechanistic link between the impact of different diets and the course of PCa development and progression. C1 [Labbe, D. P.; Zadra, G.; Kantoff, P. W.; Loda, M.; Brown, M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Labbe, D. P.; Brown, M.] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02115 USA. [Zadra, G.; Loda, M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. [Ebot, E. M.; Mucci, L. A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Mucci, L. A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, Boston, MA 02215 USA. RP Brown, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,D730, Boston, MA 02215 USA. EM myles_brown@dfci.harvard.edu OI Brown, Myles/0000-0002-8213-1658 FU Canadian Institute of Health Research (CIHR) Fellowship; National Cancer Institute [1P01CA163227, P50CA090381] FX We thank Edward L Giovannucci, Thomas Westerling, Luz E Tavera-Mendoza and Sonal Jhaveri for the critical review of this manuscript. DPL is a recipient of a Canadian Institute of Health Research (CIHR) Fellowship. LAM was a Young Investigator of the Prostate Cancer Foundation. This work was supported by grants from the National Cancer Institute (1P01CA163227 to MB and P50CA090381 to MB and PWK). NR 131 TC 7 Z9 7 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD SEP 3 PY 2015 VL 34 IS 36 BP 4683 EP 4691 DI 10.1038/onc.2014.422 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA CQ9JU UT WOS:000360931500002 PM 25531313 ER PT J AU Gilbert, GE Novakovic, VA Shi, JL Rasmussen, J Pipe, SW AF Gilbert, Gary E. Novakovic, Valerie A. Shi, Jialan Rasmussen, Jan Pipe, Steven W. TI Platelet binding sites for factor VIII in relation to fibrin and phosphatidylserine SO BLOOD LA English DT Article ID VON-WILLEBRAND-FACTOR; ACTIVATED HUMAN-PLATELETS; HUMAN-FACTOR-V; MEMBRANE-BINDING; PHOSPHOLIPID-MEMBRANES; MONOCLONAL-ANTIBODIES; BLOOD-COAGULATION; CRYSTAL-STRUCTURE; ENZYME COMPLEXES; FACTOR-X AB Thrombin-stimulated platelets expose very little phosphatidylserine (PS) but express binding sites for factor VIII (fVIII), casting doubt on the role of exposed PS as the determinant of binding sites. We previously reported that fVIII binding sites are increased three- to sixfold when soluble fibrin (SF) binds the alpha(IIb)beta(3) integrin. This study focuses on the hypothesis that platelet-bound SF is the major source of fVIII binding sites. Less than 10% of fVIII was displaced from thrombin-stimulated platelets by lactadherin, a PS-binding protein, and an fVIII mutant defective in PS-dependent binding retained platelet affinity. Therefore, PS is not the determinant of most binding sites. FVIII bound immobilized SF and paralleled platelet binding in affinity, dependence on separation from von Willebrand factor, and mediation by the C2 domain. SF also enhanced activity of fVIII in the factor Xase complex by two-to fourfold. Monoclonal antibody (mAb) ESH8, against the fVIII C2 domain, inhibited binding of fVIII to SF and platelets but not to PS-containing vesicles. Similarly, mAb ESH4 against the C2 domain, inhibited >90% of platelet-dependent fVIII activity vs 35% of vesicle-supported activity. These results imply that platelet-bound SF is a component of functional fVIII binding sites. C1 [Gilbert, Gary E.; Novakovic, Valerie A.; Shi, Jialan] VA Boston Healthcare Syst, Dept Med, Boston, MA USA. [Gilbert, Gary E.; Novakovic, Valerie A.; Shi, Jialan] VA Boston Healthcare Syst, Dept Res, Boston, MA USA. [Gilbert, Gary E.; Shi, Jialan] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Gilbert, Gary E.; Shi, Jialan] Harvard Univ, Sch Med, Boston, MA USA. [Rasmussen, Jan] Univ Aarhus, Dept Mol Biol, Prot Chem Lab, Aarhus, Denmark. [Pipe, Steven W.] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. [Pipe, Steven W.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. RP Gilbert, GE (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM gary_gilbert@hms.harvard.edu FU Department of Veterans Affairs; Baxter Healthcare FX This study was supported by a Department of Veterans Affairs grant to G.E.G. and a research grant from Baxter Healthcare. The authors are indebted to James Morrissey, Stephanie Smith, John (Pete) Lollar, and Shannon Meeks for helpful discussions and sharing reagents early in the course of these studies. NR 44 TC 4 Z9 4 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD SEP 3 PY 2015 VL 126 IS 10 BP 1237 EP 1244 DI 10.1182/blood-2015-01-620245 PG 8 WC Hematology SC Hematology GA CQ3YH UT WOS:000360540100016 PM 26162408 ER PT J AU Richly, H Kim, TM Schuler, M Kim, DW Harrison, SJ Shaw, AT Boral, AL Yovine, A Solomon, B AF Richly, Heike Kim, Tae Min Schuler, Martin Kim, Dong-Wan Harrison, Simon J. Shaw, Alice T. Boral, Anthony L. Yovine, Alejandro Solomon, Benjamin TI Ceritinib in patients with advanced anaplastic lymphoma kinase-rearranged anaplastic large-cell lymphoma SO BLOOD LA English DT Letter C1 [Richly, Heike; Schuler, Martin] Univ Hosp Essen, West German Canc Ctr, Essen, Germany. [Kim, Tae Min; Kim, Dong-Wan] Seoul Natl Univ Hosp, Seoul 110744, South Korea. [Harrison, Simon J.; Solomon, Benjamin] Peter MacCallum Canc Ctr, East Melbourne, Vic, Australia. [Shaw, Alice T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Boral, Anthony L.] Novartis Inst BioMed Res, Cambridge, MA USA. [Yovine, Alejandro] Novartis Pharma AG, Basel, Switzerland. RP Richly, H (reprint author), Univ Duisburg Essen, Univ Hosp Essen, West German Canc Ctr, Dept Med Oncol, Hufelandstr 55, D-45122 Essen, Germany. EM heike.richly@uk-essen.de NR 10 TC 2 Z9 2 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 SEP 3 PY 2015 VL 126 IS 10 BP 1257 EP 1258 DI 10.1182/blood-2014-12-617779 PG 2 WC Hematology SC Hematology GA CQ3YH UT WOS:000360540100020 PM 26337354 ER PT J AU Durst, R Sauls, K Peal, DS deVlaming, A Toomer, K Leyne, M Salani, M Talkowski, ME Brand, H Perrocheau, M Simpson, C Jett, C Stone, MR Charles, F Chiang, C Lynch, SN Bouatia-Naji, N Delling, FN Freed, LA Tribouilloy, C Le Tourneau, T LeMarec, H Fernandez-Friera, L Solis, J Trujillano, D Ossowski, S Estivill, X Dina, C Bruneval, P Chester, A Schott, JJ Irvine, KD Mao, YP Wessels, A Motiwala, T Puceat, M Tsukasaki, Y Menick, DR Kasiganesan, H Nie, XJ Broome, AM Williams, K Johnson, A Markwald, RR Jeunemaitre, X Hagege, A Levine, RA Milan, DJ Norris, RA Slaugenhaupt, SA AF Durst, Ronen Sauls, Kimberly Peal, David S. deVlaming, Annemarieke Toomer, Katelynn Leyne, Maire Salani, Monica Talkowski, Michael E. Brand, Harrison Perrocheau, Maelle Simpson, Charles Jett, Christopher Stone, Matthew R. Charles, Florie Chiang, Colby Lynch, Stacey N. Bouatia-Naji, Nabila Delling, Francesca N. Freed, Lisa A. Tribouilloy, Christophe Le Tourneau, Thierry LeMarec, Herve Fernandez-Friera, Leticia Solis, Jorge Trujillano, Daniel Ossowski, Stephan Estivill, Xavier Dina, Christian Bruneval, Patrick Chester, Adrian Schott, Jean-Jacques Irvine, Kenneth D. Mao, Yaopan Wessels, Andy Motiwala, Tahirali Puceat, Michel Tsukasaki, Yoshikazu Menick, Donald R. Kasiganesan, Harinath Nie, Xingju Broome, Ann-Marie Williams, Katherine Johnson, Amanda Markwald, Roger R. Jeunemaitre, Xavier Hagege, Albert Levine, Robert A. Milan, David J. Norris, Russell A. Slaugenhaupt, Susan A. TI Mutations in DCHS1 cause mitral valve prolapse SO NATURE LA English DT Article ID ECHOCARDIOGRAPHIC EVIDENCE; HUMAN GENOMES; FILAMIN-A; HEART; REGURGITATION; EXPRESSION; DISEASE; GENE; QUANTIFICATION; IDENTIFICATION AB Mitral valve prolapse (MVP) is a common cardiac valve disease that affects nearly 1 in 40 individuals(1-3). It can manifest as mitral regurgitation and is the leading indication for mitral valve surgery(4,5). Despite a clear heritable component, the genetic aetiology leading to non-syndromic MVP has remained elusive. Four affected individuals from a large multigenerational family segregating non-syndromic MVP underwent capture sequencing of the linked interval on chromosome 11. We report a missense mutation in the DCHS1 gene, the human homologue of the Drosophila cell polarity gene dachsous (ds), that segregates with MVP in the family. Morpholino knockdown of the zebrafish homologue dachsous1b resulted in a cardiac atrioventricular canal defect that could be rescued by wild-type human DCHS1, but not by DCHS1 messenger RNA with the familial mutation. Further genetic studies identified two additional families in which a second deleterious DCHS1 mutation segregates with MVP. Both DCHS1 mutations reduce protein stability as demonstrated in zebrafish, cultured cells and, notably, in mitral valve interstitial cells (MVICs) obtained during mitral valve repair surgery of a proband. Dchs1(+/-) mice had prolapse of thickened mitral leaflets, which could be traced back to developmental errors in valve morphogenesis. DCHS1 deficiency in MVP patient MVICs, as well as in Dchs1(+/-) mouse MVICs, result in altered migration and cellular patterning, supporting these processes as aetiological underpinnings for the disease. Understanding the role of DCHS1 in mitral valve development and MVP pathogenesis holds potential for therapeutic insights for this very common disease. C1 [Durst, Ronen; Leyne, Maire; Salani, Monica; Talkowski, Michael E.; Brand, Harrison; Simpson, Charles; Jett, Christopher; Stone, Matthew R.; Charles, Florie; Chiang, Colby; Milan, David J.; Slaugenhaupt, Susan A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Res Inst, Boston, MA 02114 USA. [Durst, Ronen; Leyne, Maire; Salani, Monica; Talkowski, Michael E.; Brand, Harrison; Simpson, Charles; Jett, Christopher; Stone, Matthew R.; Charles, Florie; Chiang, Colby; Milan, David J.; Slaugenhaupt, Susan A.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Durst, Ronen] Hadassah Hebrew Univ, Med Ctr, Div Cardiol, Jerusalem, Israel. [Sauls, Kimberly; deVlaming, Annemarieke; Toomer, Katelynn; Wessels, Andy; Motiwala, Tahirali; Williams, Katherine; Johnson, Amanda; Markwald, Roger R.; Norris, Russell A.] Med Univ S Carolina, Childrens Res Inst, Cardiovasc Dev Biol Ctr, Dept Regenerat Med & Cell Biol,Dept Med, Charleston, SC 29425 USA. [Peal, David S.; Lynch, Stacey N.; Milan, David J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr,Cardiol Div, Boston, MA 02114 USA. [Talkowski, Michael E.; Brand, Harrison] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Perrocheau, Maelle; Bouatia-Naji, Nabila; Jeunemaitre, Xavier; Hagege, Albert] Paris Cardiovasc Res Ctr, INSERM, UMR 970, F-75015 Paris, France. [Bouatia-Naji, Nabila; Jeunemaitre, Xavier; Hagege, Albert; Levine, Robert A.] Univ Paris 05, Sorbonne Paris Cite, Fac Med, F-75006 Paris, France. [Delling, Francesca N.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Cardiovasc Div, Boston, MA 02215 USA. [Freed, Lisa A.] Yale Univ, Sch Med, Heart & Vasc Ctr, Yale New Haven Hosp, New Haven, CT 06510 USA. [Tribouilloy, Christophe] Univ Hosp Amiens, Dept Cardiol, F-80000 Amiens, France. [Tribouilloy, Christophe] Jules Verne Univ Picardie, U 1088, INSERM, F-80000 Amiens, France. [Le Tourneau, Thierry; LeMarec, Herve; Dina, Christian; Schott, Jean-Jacques] INSERM, U1087, F-44007 Nantes, France. [Le Tourneau, Thierry; LeMarec, Herve; Dina, Christian; Schott, Jean-Jacques] Univ Hosp, Inst Thorax, F-44007 Nantes, France. [Fernandez-Friera, Leticia; Solis, Jorge] Ctr Nacl Invest Cardiovasc Carlos III CNIC, Madrid 28029, Spain. [Fernandez-Friera, Leticia; Solis, Jorge] Hosp Univ Monteprincipe, Madrid 28660, Spain. [Trujillano, Daniel; Estivill, Xavier] Ctr Genom Regulat, Genet Causes Dis Grp, Barcelona 08003, Catalonia, Spain. [Trujillano, Daniel; Ossowski, Stephan; Estivill, Xavier] UPF, Barcelona 08002, Catalonia, Spain. [Trujillano, Daniel; Estivill, Xavier] Hosp del Mar, Med Res Inst, IMIM, Barcelona 08003, Catalonia, Spain. [Trujillano, Daniel; Estivill, Xavier] CIBER Epidemiol & Publ Hlth CIBERESP, Barcelona 08036, Catalonia, Spain. [Ossowski, Stephan] CRG, Genom & Epigen Variat Dis Grp, Barcelona 08003, Catalonia, Spain. [Dina, Christian; Schott, Jean-Jacques] CNRS, UMR 6291, F-44007 Nantes, France. [Dina, Christian; Schott, Jean-Jacques] Univ Nantes, F-44322 Nantes, France. [Dina, Christian; Schott, Jean-Jacques] CHU Nantes, Serv Cardiol, Inst Thorax, F-44093 Nantes, France. [Bruneval, Patrick] Hop Europe Georges Pompidou, Serv Anat Pathol, F-75015 Paris, France. [Chester, Adrian] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Heart Sci Ctr, London SW7 2AZ, England. [Irvine, Kenneth D.; Mao, Yaopan] Rutgers State Univ, Waksman Inst, Howard Hughes Med Inst, Piscataway, NJ 08854 USA. [Irvine, Kenneth D.; Mao, Yaopan] Rutgers State Univ, Dept Mol Biol & Biochem, Piscataway, NJ 08854 USA. [Puceat, Michel] Aix Marseille Univ, Med Sch La Timone, Team Physiopathol Cardiac Dev, INSERM,UMR S910, F-13885 Marseille, France. [Tsukasaki, Yoshikazu] Univ Texas Hlth Ctr Tyler Northeast Tyler, Dept Cellular & Mol Biol, Tyler, TX 75708 USA. [Menick, Donald R.; Kasiganesan, Harinath] Med Univ S Carolina, Div Cardiol, Dept Med, Gazes Cardiac Res Inst, Charleston, SC 29425 USA. [Nie, Xingju; Broome, Ann-Marie] Med Univ S Carolina, Dept Radiol & Radiol Sci, Charleston, SC 29425 USA. [Jeunemaitre, Xavier] Hop Europeen Georges Pompidou, AP HP, AP HP, F-75015 Paris, France. [Hagege, Albert] Hop Europeen Georges Pompidou, AP HP, Dept Cardiol, F-75015 Paris, France. [Levine, Robert A.] Harvard Univ, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, Boston, MA 02114 USA. RP Slaugenhaupt, SA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Res Inst, Boston, MA 02114 USA. EM norrisra@musc.edu; slaugenhaupt@chgr.mgh.harvard.edu RI Schott, jean-Jacques/F-8842-2013; Le Marec, Herve/D-2718-2015; Dina, Christian/D-3535-2015; Estivill, Xavier/A-3125-2013; BOUATIA-NAJI, NABILA/D-5863-2013; OI Le Marec, Herve/0000-0002-8288-8693; Dina, Christian/0000-0002-7722-7348; Estivill, Xavier/0000-0002-0723-2256; Bouatia-Naji, Nabila/0000-0001-5424-2134; PUCEAT, michel/0000-0001-9055-7563; Chiang, Colby/0000-0002-4113-6065 FU Fondation Leducq (Paris, France) Mitral Transatlantic Network of Excellence grant [07CVD04]; Innovation in Clinical Research award of the Doris Duke Charitable Foundation; Aetna Quality Care Research Fund; National Heart Lung and Blood Institute Resequencing and Genotyping (RSG) Service; National Institutes of Health from the Extramural Research Facilities Program of the National Center for Research Resources [C06 RR018823]; French Society of Cardiology; National Heart Lung and Blood Institute [R01HL122906-01, R01-HL33756, COBRE 1P30 GM103342, 8P20 GM103444-07, R01-HL109004, R01-HL127692, RO1-HL095696]; VA Merit Review [BX002327]; National Institute of Mental Health [R00-MH095867]; Hassenfeld Scholar Program; March of Dimes; M.G.H. Scholars Program; American Heart Association [09GRNT2060075, 11SDG5270006, 2261354, 15GRNT25080052]; National Science Foundation [EPS-0903795]; NHLBI [K24 HL67434, R01HL72265, R01HL109506]; Ellison Foundation, Boston, MA; Howard Hughes Medical Institute FX This work was supported by the Fondation Leducq (Paris, France) Mitral Transatlantic Network of Excellence grant 07CVD04. MVP patient studies were supported by an Innovation in Clinical Research award of the Doris Duke Charitable Foundation, by an award of the Aetna Quality Care Research Fund, and by a gift from Rena M. Shulsky, New York, New York (S.A.S. and R.A.L.). Sequencing of the candidate region was performed at the Venter Institute through a grant from the National Heart Lung and Blood Institute Resequencing and Genotyping (RS&G) Service (S.A.S.). The work at MUSC was performed in a facility constructed with support from the National Institutes of Health, Grant Number C06 RR018823 from the Extramural Research Facilities Program of the National Center for Research Resources. Collection of the MVP France cohort was supported by the French Society of Cardiology. Other funding sources: National Heart Lung and Blood Institute: R01HL122906-01 (A.W.), R01-HL33756 (R.R.M.), COBRE 1P30 GM103342 (R.R.M., R.A.N., A.W.), 8P20 GM103444-07 (R.R.M. and R.A.N.), R01-HL109004 (D.J.M.), R01-HL127692 (D.J.M., S.A.S., R.A.N., R.A.L.); RO1-HL095696 (D.R.M.), VA Merit Review BX002327 (D.R.M.); National Institute of Mental Health R00-MH095867 (M.E.T.) The Hassenfeld Scholar Program (D.J.M.); The March of Dimes (M.E.T.); M.G.H. Scholars Program (S.A.S., M.E.T.); American Heart Association: 09GRNT2060075 (A.W.), 11SDG5270006 (R.A.N.), 2261354 (D.J.M.), 15GRNT25080052 (R.A.N.); National Science Foundation: EPS-0903795 (R.R.M.); NHLBI K24 HL67434, R01HL72265 and R01HL109506 and the Ellison Foundation, Boston, MA (R.A.L.), Howard Hughes Medical Institute (K.D.I.), and a gift from Michael Zak (D.J.M.). Thanks to T. Brown (MUSC) for his guidance on MRI studies, C. Hanscom (M.G.H.) for assistance with genomic libraries, and E. Lim (H.M.S.) for contributions in interpreting the exome mutation data. The authors would like to thank the Exome Aggregation Consortium and the groups that provided exome variant data for comparison. A full list of contributing groups can be found at http://exac.broadinstitute.org/about. NR 40 TC 11 Z9 13 U1 0 U2 19 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 SEP 3 PY 2015 VL 525 IS 7567 BP 109 EP + DI 10.1038/nature14670 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ4SE UT WOS:000360594100035 PM 26258302 ER PT J AU Dong, JC Panchakshari, RA Zhang, TT Zhang, Y Hu, JZ Volpi, SA Meyers, RM Ho, YJ Du, Z Robbiani, DF Meng, FL Gostissa, M Nussenzweig, MC Manis, JP Alt, FW AF Dong, Junchao Panchakshari, Rohit A. Zhang, Tingting Zhang, Yu Hu, Jiazhi Volpi, Sabrina A. Meyers, Robin M. Ho, Yu-Jui Du, Zhou Robbiani, Davide F. Meng, Feilong Gostissa, Monica Nussenzweig, Michel C. Manis, John P. Alt, Frederick W. TI Orientation-specific joining of AID-initiated DNA breaks promotes antibody class switching SO NATURE LA English DT Article ID B-CELLS; REGION RECOMBINATION; V(D)J RECOMBINATION; CHROMOSOME BREAKS; TRANSLOCATIONS; MECHANISMS; RESECTION; LYMPHOMA; 53BP1; REARRANGEMENTS AB During B-cell development, RAG endonuclease cleaves immunoglobulin heavy chain (IgH) V, D, and J gene segments and orchestrates their fusion as deletional events that assemble a V(D) J exon in the same transcriptional orientation as adjacent C mu constant region exons(1,2). In mice, six additional sets of constant region exons (C(H)s) lie 100-200 kilobases downstream in the same transcriptional orientation as V(D) J and C mu exons(2). Long repetitive switch (S) regions precede C mu and downstream C(H)s. In mature B cells, class switch recombination (CSR) generates different antibody classes by replacing C mu with a downstream C-H (ref. 2). Activation-induced cytidine deaminase (AID) initiates CSR by promoting deamination lesions within S mu and a downstream acceptor S region(2,3); these lesions are converted into DNA double-strand breaks (DSBs) by general DNA repair factors(3). Productive CSR must occur in a deletional orientation by joining the upstream end of an S mu DSB to the downstream end of an acceptor S-region DSB. However, the relative frequency of deletional to inversional CSR junctions has not been measured. Thus, whether orientation-specific joining is a programmed mechanistic feature of CSR as it is for V(D) J recombination and, if so, how this is achieved is unknown. To address this question, we adapt high-throughput genome-wide translocation sequencing(4) into a highly sensitive DSB end-joining assay and apply it to endogenous AID-initiated S-region DSBs in mouse B cells. We show that CSR is programmed to occur in a productive deletional orientation and does so via an unprecedented mechanism that involves in cis Igh organizational features in combination with frequent S-region DSBs initiated by AID. We further implicate ATM-dependent DSB-response factors in enforcing this mechanism and provide an explanation of why CSR is so reliant on the 53BP1 DSB-response factor. C1 [Dong, Junchao; Panchakshari, Rohit A.; Zhang, Tingting; Zhang, Yu; Hu, Jiazhi; Meyers, Robin M.; Ho, Yu-Jui; Du, Zhou; Meng, Feilong; Gostissa, Monica; Alt, Frederick W.] Harvard Univ, Sch Med, Boston Childrens Hosp, Howard Hughes Med Inst,Program Cellular & Mol Med, Boston, MA 02115 USA. [Dong, Junchao; Panchakshari, Rohit A.; Zhang, Tingting; Zhang, Yu; Hu, Jiazhi; Meyers, Robin M.; Ho, Yu-Jui; Du, Zhou; Meng, Feilong; Gostissa, Monica; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Volpi, Sabrina A.; Manis, John P.] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA 02115 USA. [Volpi, Sabrina A.; Manis, John P.] Harvard Univ, Sch Med, Joint Program Transfus Med, Boston, MA 02115 USA. [Robbiani, Davide F.; Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst, Lab Mol Immunol, New York, NY 10065 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Howard Hughes Med Inst,Program Cellular & Mol Med, Boston, MA 02115 USA. EM manis@enders.tch.harvard.edu; alt@enders.tch.harvard.edu RI Dong, Junchao/G-5719-2016 OI Dong, Junchao/0000-0001-7404-3562 FU National Institute of Health [AI077595, CA133781, AI112602, AI037526, AI072529]; NIH [T32HL066987]; Robertson Foundation/Cancer Research Institute Irvington Fellowship FX We thank K. Yu for providing the CH12F3-RMCE (1F7) cell line and exchange cassette plasmid. This work was supported by National Institute of Health grants AI077595 to F.W.A., CA133781 to J.M., AI112602 to D.F.R., and AI037526 and AI072529 to M.C.N. S.V. was supported by NIH training grant T32HL066987. F.W.A. and M.C.N. are investigators of the Howard Hughes Medical Institute. J.H. is supported by a Robertson Foundation/Cancer Research Institute Irvington Fellowship. F.M. is a Lymphoma Research Foundation postdoctoral fellow and was a Cancer Research Institute postdoctoral fellow. NR 40 TC 18 Z9 19 U1 2 U2 19 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 SEP 3 PY 2015 VL 525 IS 7567 BP 134 EP + DI 10.1038/nature14970 PG 22 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ4SE UT WOS:000360594100040 PM 26308889 ER PT J AU Peacock, G Iezzoni, LI Harkin, TR AF Peacock, Georgina Iezzoni, Lisa I. Harkin, Thomas R. TI Health Care for Americans with Disabilities-25 Years after the ADA SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Peacock, Georgina] CDC, Natl Ctr Birth Defects & Dev Disabil, Div Human Dev & Disabil, Atlanta, GA 30333 USA. [Iezzoni, Lisa I.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Iezzoni, Lisa I.] Harvard Univ, Sch Med, Med, Boston, MA USA. [Harkin, Thomas R.] US Senator, Ames, IA USA. RP Peacock, G (reprint author), CDC, Natl Ctr Birth Defects & Dev Disabil, Div Human Dev & Disabil, Atlanta, GA 30333 USA. FU Intramural CDC HHS [CC999999] NR 5 TC 2 Z9 2 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 3 PY 2015 VL 373 IS 10 BP 892 EP 893 DI 10.1056/NEJMp1508854 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CQ2OB UT WOS:000360439500004 PM 26225616 ER PT J AU Topulos, GP Greene, MF Drazen, JM AF Topulos, George P. Greene, Michael F. Drazen, Jeffrey M. TI Planned Parenthood at Risk SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Topulos, George P.] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. [Topulos, George P.] Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Greene, Michael F.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA USA. RP Topulos, GP (reprint author), Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. NR 3 TC 5 Z9 5 U1 0 U2 7 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 SEP 3 PY 2015 VL 373 IS 10 BP 963 EP 963 DI 10.1056/NEJMe1510281 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CQ2OB UT WOS:000360439500013 PM 26267451 ER PT J AU Boasso, A Overstreet, S Ruscher, JB AF Boasso, Alyssa Overstreet, Stacy Ruscher, Janet B. TI Community Disasters and Shared Trauma: Implications of Listening to Co-Survivor Narratives SO JOURNAL OF LOSS & TRAUMA LA English DT Article DE posttraumatic stress; community disasters; trauma narratives; shared trauma; social support ID POSTTRAUMATIC-STRESS-DISORDER; VICARIOUS TRAUMATIZATION; PTSD; DISCLOSURE; SYMPTOMS; RISK AB Shared trauma produces a unique dynamic in survivor-social supporter interactions because survivors may simultaneously act as support providers. We investigated people's reactions to simulated co-survivors' trauma narratives and hypothesized that the narrator's vocal distress would result in agitation and that posttraumatic stress (PTS) symptoms would moderate this relationship. Eighty-four Hurricane Katrina survivors reported their mental health, listened to an ostensible co-survivor's trauma narrative, and reported their distress. When the narrator sounded distraught rather than recovered, people with higher PTS symptoms were increasingly reactive. Results provide preliminary evidence that interactions centered on disaster experiences may create distress rather than foster recovery. C1 [Boasso, Alyssa; Overstreet, Stacy; Ruscher, Janet B.] Tulane Univ, Dept Psychol, New Orleans, LA 70118 USA. RP Boasso, A (reprint author), VA Boston Healthcare Syst, Boston, MA 02130 USA. EM aboasso@tulane.edu FU Tulane University's Center for Public Service; Robert E. Flowerree Tulane Psychology Fund FX This research was supported by a grant from Tulane University's Center for Public Service and the Robert E. Flowerree Tulane Psychology Fund. NR 29 TC 1 Z9 1 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1532-5024 EI 1532-5032 J9 J LOSS TRAUMA JI J. Loss Trauma PD SEP 3 PY 2015 VL 20 IS 5 BP 397 EP 409 DI 10.1080/15325024.2014.912055 PG 13 WC Psychology, Social SC Psychology GA CP1HQ UT WOS:000359627300001 ER PT J AU Warner, JJP AF Warner, Jon J. P. TI The Bankart Procedure: An Unrealized Expectation for Long-Term Shoulder Stability Commentary on an article by Philipp Moroder, MD, et al.: "Open Bankart Repair for the Treatment of Anterior Shoulder Instability without Substantial Osseous Glenoid Defects: Results After a Minimum Follow-up of Twenty Years" SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Editorial Material ID STABILIZATION; LATARJET C1 [Warner, Jon J. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Warner, JJP (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 EI 1535-1386 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD SEP 2 PY 2015 VL 97A IS 17 AR UNSP e61 DI 10.2106/JBJS.O.00733 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CY4SH UT WOS:000366398000003 PM 26333746 ER PT J AU Hook, G Jacobsen, JS Grabstein, K Kindy, M Hook, V AF Hook, Gregory Jacobsen, J. Steven Grabstein, Kenneth Kindy, Mark Hook, Vivian TI Cathepsin B is a New Drug Target for Traumatic Brain injury Therapeutics: evidence for E64d as a Promising Lead Drug Candidate SO FRONTIERS IN NEUROLOGY LA English DT Review DE traumatic brain injury; cathepsin B; protease; E64d; drug; therapeutics ID CYSTEINE PROTEASE INHIBITOR; AMYOTROPHIC-LATERAL-SCLEROSIS; MIDDLE CEREBRAL-ARTERY; TUMOR-NECROSIS-FACTOR; SPINAL-CORD-INJURY; LYSOSOMAL MEMBRANE PERMEABILIZATION; HIPPOCAMPAL NEURONAL DEATH; PYROGLUTAMATE AMYLOID-BETA; IMPROVES MEMORY DEFICITS; PH-INDUCED INACTIVATION AB There is currently no therapeutic drug treatment for traumatic brain injury (TBI) despite decades of experimental clinical trials. This may be because the mechanistic pathways for improving TBI outcomes have yet to be identified and exploited. As such, there remains a need to seek out new molecular targets and their drug candidates to find new treatments for TBI. This review presents supporting evidence for cathepsin B, a cysteine protease, as a potentially important drug target for TBI. Cathepsin B expression is greatly up-regulated in TBI animal models, as well as in trauma patients. Importantly, knockout of the cathepsin B gene in TBI mice results in substantial improvements of TBI-caused deficits in behavior, pathology, and biomarkers, as well as improvements in related injury models. During the process of TBI-induced injury, cathepsin B likely escapes the lysosome, its normal subcellular location, into the cytoplasm or extracellular matrix (ECM) where the unleashed proteolytic power causes destruction via necrotic, apoptotic, autophagic, and activated glia-induced cell death, together with ECM breakdown and inflammation. Significantly, chemical inhibitors of cathepsin B are effective for improving deficits in TBI and related injuries including ischemia, cerebral bleeding, cerebral aneurysm, edema, pain, infection, rheumatoid arthritis, epilepsy, Huntington's disease, multiple sclerosis, and Alzheimer's disease. The inhibitor E64d is unique among cathepsin B inhibitors in being the only compound to have demonstrated oral efficacy in a TBI model and prior safe use in man and as such it is an excellent tool compound for preclinical testing and clinical compound development. These data support the conclusion that drug development of cathepsin B inhibitors for TBI treatment should be accelerated. C1 [Hook, Gregory] Amer Life Sci Pharmaceut Inc, San Diego, CA USA. [Jacobsen, J. Steven] AstraZeneca Neurosci iMed, Cambridge, MA USA. [Grabstein, Kenneth] Univ Washington, Dept Chem Engn, Seattle, WA 98195 USA. [Kindy, Mark] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Kindy, Mark] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. [Hook, Vivian] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA. [Hook, Vivian] Univ Calif San Diego, Dept Pharmacol, Dept Neurosci, La Jolla, CA 92093 USA. RP Hook, V (reprint author), Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, 9500 Gilman Dr MC 0719, San Diego, CA 92093 USA. EM vhook@ucsd.edu FU United States National Institutes of Health (NIH) [R44AG032784]; NIH [R21AG042828, ES016774-01, R21AG043718, 1P20GM109091, 2P20GM103444, 5P30GM103342]; United States Veterans Administration (VA) [1I01RX001450, 1I01RX000331]; NSF [IIP-0903795] FX The authors wish to thank Professor Tetsumori Yamashima at the Kanazawa University Graduate School of Medical Science, Kanazawa, Japan, for his insightful discussions. This work was supported in part by the United States National Institutes of Health (NIH) grants R44AG032784 (to American Life Science Pharmaceuticals, ALSP), NIH R21AG042828 (to VH), and the United States Veterans Administration (VA) Merit Reviews 1I01RX001450 and 1I01RX000331, NIH grants ES016774-01, R21AG043718, 1P20GM109091, 2P20GM103444, and 5P30GM103342, and NSF grants IIP-0903795 (to MK). MK is a Senior Research Career Scientist in the VA. NR 309 TC 7 Z9 8 U1 1 U2 15 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 SEP 2 PY 2015 VL 6 AR 178 DI 10.3389/fneur.2015.00178 PG 27 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CV0GG UT WOS:000363927400001 PM 26388830 ER PT J AU Blumenthal, DM Orav, EJ Jena, AB Dudzinski, DM Le, ST Jha, AK AF Blumenthal, Daniel M. Orav, E. John Jena, Anupam B. Dudzinski, David M. Le, Sidney T. Jha, Ashish K. TI y Access, quality, and costs of care at physician owned hospitals in the United States: observational study SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Article ID SPECIALTY HOSPITALS; CORONARY REVASCULARIZATION; MEDICARE BENEFICIARIES; CARDIAC HOSPITALS; MORTALITY-RATES; ASSOCIATION; OWNERSHIP; SURGERY; TOO AB OBJECTIVE To compare physician owned hospitals (POHs) with non-POHs on metrics around patient populations, quality of care, costs, and payments. DESIGN Observational study. SETTING Acute care hospitals in 95 hospital referral regions in the United States, 2010. PARTICIPANTS 2186 US acute care hospitals (219 POHs and 1967 non-POHs). MAIN OUTCOME MEASURES Proportions of patients using Medicaid and those from ethnic and racial minority groups; hospital performance on patient experience metrics, care processes, risk adjusted 30 day mortality, and readmission rates; costs of care; care payments; and Medicare market share. RESULTS The 219 POHs were more often small (<100 beds), for profit, and in urban areas. 120 of these POHs were general (non-specialty) hospitals. Compared with patients from non-POHs, those from POHs were younger (77.4 v 78.4 years, P<0.001), less likely to be admitted through an emergency department (23.2% v. 29.0%, P<0.001), equally likely to be black (5.1% v 5.5%, P=0.85) or to use Medicaid (14.9% v 15.4%, P=0.75), and had similar numbers of chronic diseases and predicted mortality scores. POHs and non-POHs performed similarly on patient experience scores, processes of care, risk adjusted 30 day mortality, 30 day readmission rates, costs, and payments for acute myocardial infarction, congestive heart failure, and pneumonia. CONCLUSION Although POHs may treat slightly healthier patients, they do not seem to systematically select more profitable or less disadvantaged patients or to provide lower value care. C1 [Blumenthal, Daniel M.; Dudzinski, David M.] Massachusetts Gen Hosp, Dept Internal Med, Div Cardiol, Boston, MA 02114 USA. [Orav, E. John] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Jena, Anupam B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Le, Sidney T.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Jha, Ashish K.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Blumenthal, DM (reprint author), Massachusetts Gen Hosp, Dept Internal Med, Div Cardiol, Boston, MA 02114 USA. EM dblumenthal1@mgh.harvard.edu FU Department of Health Policy and Management at the T H Chan School of Public Health at Harvard University; Office of the Director, National Institutes of Health early independence award [1DP5OD017897-01] FX This study was funded using internal resources from the Department of Health Policy and Management at the T H Chan School of Public Health at Harvard University. ABJ reports funding from the Office of the Director, National Institutes of Health early independence award (grant 1DP5OD017897-01). NR 35 TC 2 Z9 2 U1 1 U2 3 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 SEP 2 PY 2015 VL 351 AR h4466 DI 10.1136/bmj.h4466 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CQ9JT UT WOS:000360931400002 PM 26333819 ER PT J AU Hu, K Harris, DL Yamaguchi, T von Andrian, UH Hamrah, P AF Hu, Kai Harris, Deshea L. Yamaguchi, Takefumi von Andrian, Ulrich H. Hamrah, Pedram TI A Dual Role for Corneal Dendritic Cells in Herpes Simplex Keratitis: Local Suppression of Corneal Damage and Promotion of Systemic Viral Dissemination SO PLOS ONE LA English DT Article ID VIRUS TYPE-1 LATENCY; LANGERHANS CELLS; MACROPHAGE-DEPLETION; STROMAL KERATITIS; OCULAR INFECTION; MOUSE MACROPHAGE; HSV-1 INFECTION; IMMUNE EVASION; NERVOUS-SYSTEM; LYMPH-NODES AB The cornea is the shield to the foreign world and thus, a primary site for peripheral infections. However, transparency and vision are incompatible with inflammation and scarring that may result from infections. Thus, the cornea is required to perform a delicate balance between fighting infections and preserving vision. To date, little is known about the specific role of antigen-presenting cells in viral keratitis. In this study, utilizing an established murine model of primary acute herpes simplex virus (HSV)-1 keratitis, we demonstrate that primary HSV keratitis results in increased conventional dendritic cells (cDCs) and macrophages within 24 hours after infection. Local depletion of cDCs in CD11c-DTR mice by subconjuntival diphtheria toxin injections, led to increased viral proliferation, and influx of inflammatory cells, resulting in increased scarring and clinical keratitis. In addition, while HSV infection resulted in significant corneal nerve destruction, local depletion of cDCs resulted in a much more severe loss of corneal nerves. Further, local cDC depletion resulted in decreased corneal nerve infection, and subsequently decreased and delayed systemic viral transmission in the trigeminal ganglion and draining lymph node, resulting in decreased mortality of mice. In contrast, sham depletion or depletion of macrophages through local injection of clodronate liposomes had neither a significant impact on the cornea, nor an effect on systemic viral transmission. In conclusion, we demonstrate that corneal cDCs may play a primary role in local corneal defense during viral keratitis and preserve vision, at the cost of inducing systemic viral dissemination, leading to increased mortality. C1 [Hu, Kai; Harris, Deshea L.; Yamaguchi, Takefumi; Hamrah, Pedram] Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst,Massachusetts Eye & Ear, Boston, MA 02114 USA. [Hu, Kai; Yamaguchi, Takefumi; Hamrah, Pedram] Harvard Univ, Sch Med, Dept Ophthalmol, Cornea Serv,Massachusetts Eye & Ear Infirm, Boston, MA USA. [Hu, Kai; Harris, Deshea L.; Yamaguchi, Takefumi; von Andrian, Ulrich H.; Hamrah, Pedram] Harvard Univ, Sch Med, Childrens Hosp Boston, Immune Dis Inst,Program Cellular & Mol Med, Boston, MA USA. [Harris, Deshea L.; Hamrah, Pedram] Tufts Univ, Sch Med, Dept Ophthalmol, Tufts Med Ctr, Boston, MA 02111 USA. [von Andrian, Ulrich H.] Harvard Univ, Sch Med, Div Immunol, Dept Microbiol & Immunobiol, Boston, MA USA. RP Hamrah, P (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst,Massachusetts Eye & Ear, Boston, MA 02114 USA. EM phamrah@tuftsmedicalcenter.org OI Harris, Deshea/0000-0002-8194-1827 FU NIH [K08-EY020575, R01-EY022695]; Research to Prevent Blindness Career Development Award; Falk Medical Research Trust; MEEI Foundation FX This work was supported by grants from the NIH: K08-EY020575 (PH), R01-EY022695 (PH), Research to Prevent Blindness Career Development Award (PH), Falk Medical Research Trust (PH), and MEEI Foundation (PH). NR 70 TC 4 Z9 4 U1 4 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 SEP 2 PY 2015 VL 10 IS 9 AR e0137123 DI 10.1371/journal.pone.0137123 PG 23 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ4ZT UT WOS:000360613800099 PM 26332302 ER PT J AU Luo, MY Duan, CJ Qiu, JP Li, WR Zhu, DY Cai, WL AF Luo, Mingyue Duan, Chaijie Qiu, Jianping Li, Wenru Zhu, Dongyun Cai, Wenli TI Diagnostic Value of Multidetector CT and Its Multiplanar Reformation, Volume Rendering and Virtual Bronchoscopy Postprocessing Techniques for Primary Trachea and Main Bronchus Tumors SO PLOS ONE LA English DT Article ID PICTORIAL ESSAY; ROW CT; AIRWAYS; ANGIOGRAPHY; MDCT AB Purpose To evaluate the diagnostic value of multidetector CT (MDCT) and its multiplanar reformation (MPR), volume rendering (VR) and virtual bronchoscopy (VB) postprocessing techniques for primary trachea and main bronchus tumors. Methods Detection results of 31 primary trachea and main bronchus tumors with MDCT and its MPR, VR and VB postprocessing techniques, were analyzed retrospectively with regard to tumor locations, tumor morphologies, extramural invasions of tumors, longitudinal involvements of tumors, morphologies and extents of luminal stenoses, distances between main bronchus tumors and trachea carinae, and internal features of tumors. The detection results were compared with that of surgery and pathology. Results Detection results with MDCT and its MPR, VR and VB were consistent with that of surgery and pathology, included tumor locations (tracheae, n = 19; right main bronchi, n = 6; left main bronchi, n = 6), tumor morphologies (endoluminal nodes with narrow bases, n = 2; endoluminal nodes with wide bases, n = 13; both intraluminal and extraluminal masses, n = 16), extramural invasions of tumors (brokethrough only serous membrane, n = 1; 4.0 mm-56.0 mm, n = 14; no clear border with right atelectasis, n = 1), longitudinal involvements of tumors (3.0 mm, n = 1; 5.0 mm-68.0 mm, n = 29; whole right main bronchus wall and trachea carina, n = 1), morphologies of luminal stenoses (irregular, n = 26; circular, n = 3; eccentric, n = 1; conical, n = 1) and extents (mild, n = 5; moderate, n = 7; severe, n = 19),distances between main bronchus tumors and trachea carinae (16.0 mm, n = 1; invaded trachea carina, n = 1; >20.0 mm, n = 10), and internal features of tumors (fairly homogeneous densities with rather obvious enhancements, n = 26; homogeneous density with obvious enhancement, n = 1; homogeneous density without obvious enhancement, n = 1; not enough homogeneous density with obvious enhancement, n = 1; punctate calcification with obvious enhancement, n = 1; low density without obvious enhancement, n = 1). Conclusion MDCT and its MPR, VR and VB images have respective advantages and disadvantages. Their combination could complement to each other to accurately detect locations, natures (benignancy, malignancy or low malignancy), and quantities (extramural invasions, longitudinal involvements, extents of luminal stenoses, distances between main bronchus tumors and trachea carinae) of primary trachea and main bronchus tumors with crucial information for surgical treatment, are highly useful diagnostic methods for primary trachea and main bronchus tumors. C1 [Luo, Mingyue; Qiu, Jianping; Li, Wenru; Zhu, Dongyun] Sun Yat Sen Univ, Affiliated Hosp 6, Dept Radiol, Guangzhou 510275, Guangdong, Peoples R China. [Duan, Chaijie] Tsinghua Univ, Grad Sch Shenzhen, Biomed Engn Res Ctr, Shenzhen 518057, Guangdong, Peoples R China. [Cai, Wenli] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Cai, Wenli] Harvard Univ, Sch Med, Boston, MA USA. RP Luo, MY (reprint author), Sun Yat Sen Univ, Affiliated Hosp 6, Dept Radiol, Guangzhou 510275, Guangdong, Peoples R China. EM myluo720@163.com FU National Natural Science Foundation of China [81230035]; Guangdong Provincial Science and Technology Programs [2013B051000016] FX This study was supported by National Natural Science Foundation of China (81230035) [http://www.nsfc.gov.cn/]; and Guangdong Provincial Science and Technology Programs (2013B051000016) [http://pro.gdstc.gov.cn/]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 25 TC 3 Z9 4 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 2 PY 2015 VL 10 IS 9 AR e0137329 DI 10.1371/journal.pone.0137329 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ4ZT UT WOS:000360613800121 PM 26332466 ER PT J AU Singh, JA Akhras, KS Shiozawa, A AF Singh, Jasvinder A. Akhras, Kasem S. Shiozawa, Aki TI Comparative effectiveness of urate lowering with febuxostat versus allopurinol in gout: analyses from large U.S. managed care cohort (vol 17, 120, 2015) SO ARTHRITIS RESEARCH & THERAPY LA English DT Correction C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35233 USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL 35233 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL 35233 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35233 USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN 55905 USA. [Akhras, Kasem S.; Shiozawa, Aki] Takeda Pharmaceut Int Inc, Deerfield, IL 60015 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Med Serv, 700 South 19th St, Birmingham, AL 35233 USA. EM jassingh@uab.edu FU NIAMS NIH HHS [P50 AR060772] NR 1 TC 0 Z9 0 U1 2 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PD SEP 2 PY 2015 VL 17 AR 236 DI 10.1186/s13075-015-0752-9 PG 2 WC Rheumatology SC Rheumatology GA CQ2KM UT WOS:000360428900002 PM 26330228 ER PT J AU Clardy, SM Mohan, JF Vinegoni, C Keliher, EJ Iwamoto, Y Benoist, C Mathis, D Weissleder, R AF Clardy, Susan M. Mohan, James F. Vinegoni, Claudio Keliher, Edmund J. Iwamoto, Yoshiko Benoist, Christophe Mathis, Diane Weissleder, Ralph TI Rapid, high efficiency isolation of pancreatic beta-cells SO SCIENTIFIC REPORTS LA English DT Article ID NOD MICE; PURIFICATION; REPLICATION; SIGNATURE; RECEPTOR; MASS AB The ability to isolate pure pancreatic beta-cells would greatly aid multiple areas of diabetes research. We developed a fluorescent exendin-4-like neopeptide conjugate for the rapid purification and isolation of functional mouse pancreatic beta-cells. By targeting the glucagon-like peptide-1 receptor with the fluorescent conjugate, beta-cells could be quickly isolated by flow cytometry and were >99% insulin positive. These studies were confirmed by immunostaining, microscopy and gene expression profiling on isolated cells. Gene expression profiling studies of cytofluorometrically sorted beta-cells from 4 and 12 week old NOD mice provided new insights into the genetic programs at play of different stages of type-1 diabetes development. The described isolation method should have broad applicability to the beta-cell field. C1 [Clardy, Susan M.; Vinegoni, Claudio; Keliher, Edmund J.; Iwamoto, Yoshiko; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Mohan, James F.; Benoist, Christophe; Mathis, Diane] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Benoist, Christophe; Mathis, Diane] Harvard Univ, Sch Med, Evergrande Ctr Immunol Dis, Boston, MA USA. [Benoist, Christophe; Mathis, Diane] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu FU NIH [PO1 AI54904, T32CA79443]; Juvenile Diabetes Research Foundation postdoctoral fellowship [3-2014-216] FX This research was supported by NIH grant PO1 AI54904. S.M.C. was supported by an NIH interdisciplinary training grant (T32CA79443), and J.F.M. by a Juvenile Diabetes Research Foundation postdoctoral fellowship (3-2014-216). NR 22 TC 0 Z9 0 U1 1 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 SEP 2 PY 2015 VL 5 AR 13681 DI 10.1038/srep13681 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ3YJ UT WOS:000360540400001 PM 26330153 ER PT J AU Jennings, LA Reuben, DB Kim, SB Keeler, E Roth, CP Zingmond, DS Wenger, NS Ganz, DA AF Jennings, Lee A. Reuben, David B. Kim, Sung-Bou Keeler, Emmett Roth, Carol P. Zingmond, David S. Wenger, Neil S. Ganz, David A. TI Targeting a High-Risk Group for Fall Prevention: Strategies for Health Plans SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID OLDER AMERICANS; COMMUNITY; INJURIES; CARE; ADULTS AB Objectives: Although Medicare has implemented incentives for health plans to reduce fall risk, the best way to identify older people at high risk of falling and to use screening results to target fall prevention services remains unknown. We evaluated 4 different strategies using a combination of administrative data and patient-reported information that health plans could easily obtain. Study Design: Observational study. Methods: We used data from 1776 patients 75 years or older in 4 community-based primary care practices who screened positive for a fear of falling and/or a history of falls. For these patients, we predicted fall-related injuries in the 24 months after the date of screening using claims/encounter data. After controlling for age and gender, we predicted the number of fall-related injuries by adding Elixhauser comorbidity count, any claim for a fall-related injury during the 12 months prior to screening, and falls screening question responses in a sequential fashion using negative binomial regression models. Results: Basic patient characteristics, including age and Elixhauser comorbidity count, were strong predictors of fall-related injury. Among falls screening questions, a positive response to, "Have you fallen 2 or more times in the past year?" was the most predictive of a fall-related injury (incidence rate ratio [IRR], 1.56; 95% CI, 1.25-1.94). Prior claim for a fall-related injury also independently predicted this type of injury (IRR, 1.41; 95% CI, 1.051.89). The best model for predicting fall-related injuries combined all of these approaches. Conclusions: The combination of administrative data and a simple screening item can be used by health plans to target patients at high risk for future fall-related injuries. C1 [Jennings, Lee A.; Reuben, David B.; Ganz, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Multicampus Program Geriatr Med & Gerontol, Los Angeles, CA 90095 USA. [Zingmond, David S.; Wenger, Neil S.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Kim, Sung-Bou] Pardee RAND Grad Sch, Santa Monica, CA USA. [Keeler, Emmett; Roth, Carol P.; Wenger, Neil S.; Ganz, David A.] RAND Hlth, Santa Monica, CA USA. [Ganz, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. RP Jennings, LA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, 10945 Le Conte Ave,Ste 2339, Los Angeles, CA 90095 USA. EM lajennings@mednet.ucla.edu FU National Institute on Aging [R01AG036776]; UCLA Claude Pepper Older Americans Independence Center - National Institute on Aging [(5P30AG028748)33]; NIH/National Center for Advancing Translational Science (NCATS) UCLA CTSI Grant [UL1TR000124] FX This project was supported by a grant from the National Institute on Aging (R01AG036776). Dr Jennings was supported by the UCLA Claude Pepper Older Americans Independence Center funded by the National Institute on Aging (5P30AG028748)33 and the NIH/National Center for Advancing Translational Science (NCATS) UCLA CTSI Grant Number UL1TR000124. NR 26 TC 0 Z9 0 U1 1 U2 1 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 SEP PY 2015 VL 21 IS 9 BP E519 EP + PG 14 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA DR4YF UT WOS:000379908800003 PM 26618439 ER PT J AU Rajagopal, R Shah, GK Blinder, KJ Altaweel, M Eliott, D Wee, R Cooper, B Walia, H Smith, B Joseph, DP AF Rajagopal, Rithwick Shah, Gaurav K. Blinder, Kevin J. Altaweel, Michael Eliott, Dean Wee, Raymond Cooper, Blake Walia, Harpreet Smith, Bradley Joseph, Daniel P. TI Bevacizumab Versus Ranibizumab in the Treatment of Macular Edema Due to Retinal Vein Occlusion: 6-Month Results of the CRAVE Study SO OPHTHALMIC SURGERY LASERS & IMAGING RETINA LA English DT Article; Proceedings Paper CT Annual Meeting of the Retina-Society CY SEP 11-14, 2014 CL Philadelphia, PA SP Retina Soc ID ENDOTHELIAL GROWTH-FACTOR; INTRAVITREAL AFLIBERCEPT; DEGENERATION; SECONDARY; TRIAL AB BACKGROUND AND OBJECTIVE: To compare efficacy of monthly treatment with bevacizumab or ranibizumab for macular edema due to retinal vein occlusion. PATIENTS AND METHODS: Randomized, multicenter, comparative trial (ClinicalTrials.gov identifier: NCT01428388). Participants were randomized 1: 1 to receive monthly treatment with bevacizumab or ranibizumab. The primary outcome was change in central foveal thickness at 6 months compared to baseline. RESULTS: The trial randomized 98 patients to treatment with bevacizumab or ranibizumab. At 6 months, there were no differences in change in central foveal thickness between groups (bevacizumab: mean reduction of 212.6 mu m, 95% confidence interval [CI], -288.3 to -137.0; ranibizumab: mean reduction of 243.8 mu m, 95% CI, -309.6 to -178.0; P = .72, analysis of variance [ANOVA]). Both groups showed similar functional outcomes (bevacizumab: 0.33 logMAR gain, 95% CI, -0.47 to -0.18; ranibizumab: 0.34 logMAR gain, 95% CI, -0.45 to -0.23; P =.38, ANOVA). CONCLUSION: In the treatment of retinal vein occlusion, bevacizumab and ranibizumab have similar effects on reducing macular thickness and improving visual acuity. C1 [Rajagopal, Rithwick] Washington Univ, Dept Ophthalmol & Visual Sci, St Louis, MO 63130 USA. [Shah, Gaurav K.; Blinder, Kevin J.; Walia, Harpreet; Smith, Bradley; Joseph, Daniel P.] Retina Inst, 1600 S Brentwood Blvd,Suite 800, St Louis, MO 63144 USA. [Altaweel, Michael] Univ Wisconsin, Dept Ophthalmol, Madison, WI USA. [Eliott, Dean] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Eliott, Dean] Harvard Univ, Sch Med, Boston, MA USA. [Wee, Raymond] Retina Consultants Hawaii, Honolulu, HI USA. [Cooper, Blake] Retina Associates PA, Kansas City, MO USA. RP Shah, GK (reprint author), Retina Inst, 1600 S Brentwood Blvd,Suite 800, St Louis, MO 63144 USA. EM gkshah1@gmail.com NR 15 TC 2 Z9 2 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 2325-8160 EI 2325-8179 J9 OSLI RETINA JI Ophthalmic Surg. Lasers Imag. Retin. PD SEP PY 2015 VL 46 IS 8 BP 844 EP 850 DI 10.3928/23258160-20150909-09 PG 7 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA DP9UD UT WOS:000378842000010 PM 26431300 ER PT J AU Villa, NM Li, N Yeh, MW Hurvitz, SA Dawson, NA Leung, AM AF Villa, Natalie M. Li, Ning Yeh, Michael W. Hurvitz, Sara A. Dawson, Nicole A. Leung, Angela M. TI SERUM THYROTROPIN CONCENTRATIONS ARE NOT PREDICTIVE OF AGGRESSIVE BREAST CANCER BIOLOGY IN EUTHYROID INDIVIDUALS SO ENDOCRINE PRACTICE LA English DT Article ID THYROID AUTOIMMUNITY; COLORECTAL-CANCER; DISEASES; HYPOTHYROIDISM; DISORDERS; PREVALENCE; IODINE; WOMEN; ASSOCIATION; CARCINOMA AB Objective: The potential influence of hypothyroidism on breast cancer remains incompletely understood. The objective of this study was to investigate the relationship between serum thyrotropin (thyroid-stimulating hormone, TSH) concentration and markers of aggressive breast cancer biology as defined by receptor expression profile, tumor grade, and American Joint Committee on Cancer (AJCC) stage characteristics. Methods: This was a retrospective cohort study of patients from 2002 to 2014. All breast cancer patients who had complete receptor (estrogen receptor, ER; progesterone receptor, PR; and human epidermal growth factor receptor 2, Her2/neu) and prediagnosis serum TSH data (n = 437) were included. All patients had 1 of 6 receptor profiles: ER+ PR+ Her2/neu-, ER+ PR- Her2/neu-, ER+ PR+ Her2/neu+, ER+ PR- Her2/neu+, ER- PR- Her2/neu+, or ER- PR- Her2/neu-. Log-transformed serum TSH concentrations were analyzed using multinomial and logistic regressions to identify potential relationships with markers of breast cancer aggressiveness. Results: Increasing serum TSH concentration was associated with a lower probability of having the receptor expression profile ER+ PR+ Her2/neu+ compared to patients with the ER+ PR+ Her2/neu- profile (odds ratio [OR] = 0.52, P = .0045). No significant associations between other receptor expression profiles and serum TSH concentration were found. All time-weighted and unweighted median serum TSH concentrations were within normal limits. No significant associations between serum TSH concentration and tumor grade, overall AJCC stage, tumor size (T), lymph node positivity (N), or presence of metastasis (M) were observed. Conclusions: Serum TSH was not associated with markers of breast cancer aggressiveness in our cohort. C1 [Villa, Natalie M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90073 USA. [Li, Ning] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90073 USA. [Yeh, Michael W.] Univ Calif Los Angeles, David Geffen Sch Med, Sect Endocrine Surg, Los Angeles, CA 90073 USA. [Hurvitz, Sara A.] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol Oncol, Los Angeles, CA 90073 USA. [Dawson, Nicole A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90073 USA. [Leung, Angela M.] VA Greater Los Angeles Hlth Syst, Div Endocrinol, Los Angeles, CA USA. [Leung, Angela M.] Univ Calif Los Angeles, David Geffen Sch Med, Div Endocrinol Diabet & Hypertens, 11301 Wilshire Blvd 111D, Los Angeles, CA 90073 USA. RP Leung, AM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Endocrinol Diabet & Hypertens, 11301 Wilshire Blvd 111D, Los Angeles, CA 90073 USA. EM amleung@mednet.ucla.edu FU NIH [K23HD068552]; NIH/National Center for Advancing Translational Science (NCATS) [UL1TR000124] FX This work was supported by NIH K23HD068552 (to A.M.L.) and NIH/National Center for Advancing Translational Science (NCATS) UCLA CTSI Grant Number UL1TR000124. NR 30 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X EI 1934-2403 J9 ENDOCR PRACT JI Endocr. Pract. PD SEP PY 2015 VL 21 IS 9 BP 1040 EP 1045 DI 10.4158/EP15733.OR PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DO7LX UT WOS:000377965200009 PM 26121443 ER PT J AU Yu, VWC Scadden, DT AF Yu, Vionnie W. C. Scadden, David T. TI Global transcriptome analysis of T-competent progenitors in the bone marrow SO GENOMICS DATA LA English DT Article DE Osteolineaege cells; T cells; Ly6D-common lymphoid progenitor; Osteocalcin+ cells; Bone marrow AB T cells are known to develop in the thymus. However, molecular events that control the transition from hematopoietic progenitor cells in the bone marrow to T precursor cells seeded in the thymus remained poorly defined. Our recent report showed that osteocalcin (Ocn)-expressing bone cells in the bone marrow have major impact on T cell immunity by regulating T progenitor development in the bone marrow (Yu et al., 2015) [1]. Selective endogenous depletion of Ocn(+) cells by inducible diphtheria toxin receptor expression (OcnCre;iDTR) led to reduction of T-competent common lymphoid progenitors (Ly6D(-) CLPs) in the bone marrow and loss of T cells in the thymus. Expression of the Notch ligand DLL4 by Ocn(+) cells in the bone marrow ensures the production of Ly6D(-) CLPs, and expression of chemotactic molecules CCR7 and PSGL1 to enable subsequent thymic seeding. These data indicate that specific mesenchymal cells in bone marrow provide key molecular drivers enforcing thymus-seeding progenitor generation and thereby directly link skeletal biology to the production of T cell based adaptive immunity. Here we present the transcriptome profiles of Ly6D(-) CLPs derived from Ocn(+) cells deleted mice (OcnCre(+); iDTR) compared to those derived from control littermates (OcnCre(-); iDTR). These data are publically available from NCBI Gene Expression Omnibus (GEO) with the accession number GSE66102. (C) 2015 The Authors. Published by Elsevier Inc. C1 Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. Harvard Stem Cell Inst, Cambridge, MA USA. Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. OI Yu, Vionnie W. C./0000-0002-6658-0285 FU NCI NIH HHS [C06 CA059267]; NHLBI NIH HHS [U01 HL100402, R01 HL044851, R01 HL097794] NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-5960 J9 GENOM DATA JI Genom. Data PD SEP PY 2015 VL 5 BP 100 EP 102 DI 10.1016/j.gdata.2015.05.024 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA DO4MS UT WOS:000377757800030 PM 26484235 ER PT J AU Yu, VWC Lymperi, S Ferraro, F Scadden, DT AF Yu, Vionnie W. C. Lymperi, Stefania Ferraro, Francesca Scadden, David T. TI Transcriptome comparison of distinct osteolineage subsets in the hematopoietic stem cell niche using a triple fluorescent transgenic mouse model SO GENOMICS DATA LA English DT Article DE Osteolineage cells; Osterix; Osteocalcin; Bone marrow; Niche ID BONE-MARROW; OSTEOPONTIN; PROGENITORS; COMPONENT; SIZE AB The bone marrow niche is recognized as a central player in maintaining and regulating the behavior of hematopoietic stem and progenitor cells. Specific gain-of and loss-of function experiments perturbing a range of osteolineage cells or their secreted proteins had been shown to affect stem cell maintenance (Calvi et al, 2003 [1]; Stier et al., 2005 [2]; Zhang et al., 2003 [3]; Nilsson et al., 2005 [4]; Greenbaum et al., 2013 [5]) and engraftment (Adam et al., 2006, 2009 [6,7]). We used specific in vivo cell deletion approaches to dissect the niche cell-parenchymal cell dependency in a complex bone marrow microenvironment. Endogenous deletion of osteocalcin-expressing (Ocn(+)) cells led to a loss of T immune cells (Yu et al., 2015 [8]. Ocn(+) cells express the Notch ligand DLL4 to communicate with T-competent progenitors, and thereby ensuring T precursor production and expression of chemotactic molecules on their cell surface for subsequent thymic seeding. In contrast, depletion of osterix-expressing (Osx(+)) osteoprogenitors led to reduced B immune cells. These distinct hematopoietic phenotypes suggest specific pairing of mesenchymal niche cells and parenchymal hematopoietic cells in the bone marrow to create unique functional units to support hematopoiesis. Here, we present the global gene expression profiles of these osteolineage subtypes utilizing a triple fluorescent transgenicmouse model (OsxCre(+); Rosa-mCh(+); Ocn:Topaz(+)) that labels Osx(+) cells red, Ocn(+) cells green, and Osx(+) Ocn(+) cells yellow. This system allows isolation of distinct osteolineage subsets within the same animal by flow cytometry. Array data that have been described in our study [8] are also publically available from NCBI Gene Expression Omnibus (GEO) with the accession number GSE66042. Differences in gene expression may correlate with functional difference in supporting hematopoiesis. (C) 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). C1 [Yu, Vionnie W. C.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. Harvard Stem Cell Inst, Cambridge, MA USA. Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP Yu, VWC (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. OI Yu, Vionnie W. C./0000-0002-6658-0285 FU NCI NIH HHS [C06 CA059267]; NHLBI NIH HHS [R01 HL044851, R01 HL097794, U01 HL100402] NR 9 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-5960 J9 GENOM DATA JI Genom. Data PD SEP PY 2015 VL 5 BP 318 EP 319 DI 10.1016/j.gdata.2015.06.001 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA DO4MS UT WOS:000377757800085 PM 26484277 ER PT J AU Post, RM Altshuler, L Kupka, R McElroy, SL Frye, MA Rowe, M Grunze, H Suppes, T Keck, PE Leverich, GS Nolen, WA AF Post, Robert M. Altshuler, Lori Kupka, Ralph McElroy, Susan L. Frye, Mark A. Rowe, Michael Grunze, Heinz Suppes, Trisha Keck, Paul E., Jr. Leverich, Gabriele S. Nolen, Willem A. TI Multigenerational Positive Family History of Psychiatric Disorders Is Associated With a Poor Prognosis in Bipolar Disorder SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID UNITED-STATES; CHILDHOOD ADVERSITY; MENTAL-DISORDERS; EARLY-ONSET; EARLY AGE; STEP-BD; RISK; DEPRESSION; ILLNESS; TRIAL AB The authors assessed how family history loading affected the course of illness in patients from the United States. A total of 676 outpatients with bipolar disorder from the United States rated their illness and provided a parental and grandparental history of mood disorder, substance abuse, and other clinical conditions. A positive family history for each illness was associated with almost all of the seven poor prognosis factors established in the study (abuse in childhood, early onset, anxiety and substance abuse comorbidity, rapid cycling, multiple episodes, and worsening of severity or frequency of episodes). Family history for psychiatric difficulties in parents and grandparents was associated with a more complex and difficult course of bipolar illness. C1 [Post, Robert M.; Rowe, Michael; Leverich, Gabriele S.] Bipolar Collaborat Network, Bethesda, MD USA. [Post, Robert M.] George Washington Univ, Dept Psychiat & Behav Sci, Washington, DC USA. [Altshuler, Lori] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Altshuler, Lori] West Los Angeles Healthcare Ctr, Dept Psychiat, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Kupka, Ralph] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands. [McElroy, Susan L.; Keck, Paul E., Jr.] Lindner Ctr HOPE, Mason, OH USA. [McElroy, Susan L.] Univ Cincinnati, Coll Med, Biol Psychiat Program, Cincinnati, OH USA. [Frye, Mark A.] Mayo Clin, Dept Psychiat, Rochester, MN USA. [Grunze, Heinz] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Suppes, Trisha] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. [Suppes, Trisha] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Keck, Paul E., Jr.] Univ Cincinnati, Coll Med, Dept Psychiat & Behav Neurosci, Cincinnati, OH USA. [Nolen, Willem A.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. RP Post, RM (reprint author), Bipolar Collaborat Network, Bethesda, MD USA. EM robert.post@speakeasy.net OI Grunze, Heinz/0000-0003-4712-8979 FU Stanley Medical Research Institute FX The acquisition of the initial clinical data was funded by the Stanley Medical Research Institute. NR 40 TC 6 Z9 6 U1 4 U2 5 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 FAL PY 2015 VL 27 IS 4 BP 304 EP 310 DI 10.1176/appi.neuropsych.14080204 PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA DM0ON UT WOS:000376045400008 PM 26258489 ER PT J AU Ducharme, S Murray, ED Seiner, SJ Tayeb, H Legesse, B Price, BH AF Ducharme, Simon Murray, Evan D. Seiner, Stephen J. Tayeb, Haythum Legesse, Benafew Price, Bruce H. TI Retrospective Analysis of the Short-Term Safety of ECT in Patients With Neurological Comorbidities: A Guide for Pre-ECT Neurological Evaluations SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID ELECTROCONVULSIVE-THERAPY; PARKINSONS-DISEASE; DEPRESSED-PATIENTS; MULTIPLE-SCLEROSIS; CLINICAL-EXPERIENCE; EEG ABNORMALITIES; MAJOR DEPRESSION; CASE-SERIES; HEADACHE; EFFICACY AB Pre-ECT neurology consultations are often requested to determine the relative risk of the procedure in patients with neurological comorbidities, but there is limited data to guide clinicians. The authors performed a retrospective chart review of all consecutive inpatients at McLean Hospital who underwent a pre-ECT neurological evaluation between January 2012 and June 2014 (N=68). ECT was safe and effective in patients with a wide variety of neurological diseases. Only one minor event was related to a neurological comorbidity, and there were no serious neurological complications. Based on the latest evidence, the authors provide guidance on the pre-ECT evaluation with respect to neurologic status. C1 [Ducharme, Simon] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Ducharme, Simon] McGill Univ, Montreal Neurol Inst, Dept Psychiat, Montreal, PQ, Canada. [Ducharme, Simon; Murray, Evan D.; Price, Bruce H.] McLean Hosp, Dept Neurol, Belmont, MA 02178 USA. [Ducharme, Simon; Price, Bruce H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Seiner, Stephen J.; Legesse, Benafew] McLean Hosp, Dept Psychiat, Belmont, MA 02178 USA. [Tayeb, Haythum] King Abdulaziz Univ, Dept Neurol, Jeddah 21413, Saudi Arabia. RP Ducharme, S (reprint author), McGill Univ, Ctr Hlth, Montreal, PQ, Canada. EM ulsimon.ducharme@mcgill.ca FU Sidney R. Baer Jr. Foundation; Fonds de Recherche du Quebec-Sante; McGill University Health Centre Research Institute FX This work was supported by the Sidney R. Baer Jr. Foundation. Dr. Ducharme's fellowship was supported by the Sidney R. Baer Jr. Foundation, the Fonds de Recherche du Quebec-Sante, and the McGill University Health Centre Research Institute ( Frank McGill Travel Fellowship). Dr. Ducharme, Dr. Murray, Dr. Seiner, Dr. Tayeb, Dr. Legesse, and Dr. Price report no financial relationships with commercial interests. NR 45 TC 0 Z9 0 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 FAL PY 2015 VL 27 IS 4 BP 311 EP 321 DI 10.1176/appi.neuropsych.14080195 PG 11 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA DM0ON UT WOS:000376045400009 PM 25658682 ER PT J AU DuBrock, HM Kradin, RL Rodriguez-Lopez, JM Channick, RN AF DuBrock, Hilary M. Kradin, Richard L. Rodriguez-Lopez, Josanna M. Channick, Richard N. TI Pulmonary capillary hemangiomatosis: the role of invasive cardiopulmonary exercise testing SO PULMONARY CIRCULATION LA English DT Article DE pulmonary capillary hemangiomatosis; pulmonary arterial hypertension; cardiopulmonary exercise test; intrapulmonary shunt; pulmonary arteriovenous malformation ID HEREDITARY HEMORRHAGIC TELANGIECTASIA; VENOOCCLUSIVE DISEASE; HYPERTENSION; DISORDER; AUTOPSY AB Pulmonary capillary hemangiomatosis (PCH) is a rare form of pulmonary arterial hypertension (PAH) characterized by pulmonary capillary proliferation and pseudoinvasion of collagenous septal structures. PCH is often accompanied by veno-occlusive changes and pulmonary hypertensive arterial remodeling. The clinical and pathological diagnosis of PCH can be subtle and easily missed. Most reported cases of PCH have been associated with resting PAH. We report the cases of 3 patients who initially presented with exertional dyspnea with normal to mildly elevated resting pulmonary arterial pressures and marked intrapulmonary shunting. In all 3 patients, invasive cardiopulmonary exercise testing was suggestive of pulmonary vascular disease. Owing to abnormalities on invasive exercise testing, lung biopsies were performed; these were diagnostic of PCH, and the patients were referred for lung transplantation. We describe unique features of these 3 cases-including novel pathological findings and the presence of intrapulmonary shunting in all 3 patients-and we discuss the role of cardiopulmonary exercise testing in the evaluation of PCH. C1 [DuBrock, Hilary M.; Kradin, Richard L.; Rodriguez-Lopez, Josanna M.; Channick, Richard N.] Massachusetts Gen Hosp, Div Pulm & Crit Care, Boston, MA 02114 USA. RP DuBrock, HM (reprint author), 55 Fruit St, Boston, MA 02114 USA. EM hdubrock@mgh.harvard.edu FU NHLBI NIH HHS [T32 HL007893] NR 27 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 2045-8932 EI 2045-8940 J9 PULM CIRC JI Pulm. Circ. PD SEP PY 2015 VL 5 IS 3 BP 580 EP 586 DI 10.1086/682227 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA DK9BI UT WOS:000375224400018 PM 26401260 ER PT J AU Byrd, D Mullen, L Renfro, D Harris, TA AF Byrd, Debra Mullen, Linda Renfro, David Harris, Theodore A. TI Implementing a Perioperative RN Training Program for Recent Graduates SO AORN JOURNAL LA English DT Article DE RN graduate nurse; OR; Periop 101; orientation; perioperative workforce AB In 2010, nurse educators at one health care facility implemented a new program that emphasized placing new graduates in specialty areas, including the hemodialysis unit, the gastroenterology unit, and the OR. Managers in the OR faced staffing challenges because of the difficulty in recruiting and retaining experienced perioperative nurses and the expected retirement of a significant number of staff members. Surgical services managers agreed to participate in the new graduate program and decided to use AORN's Periop 101 (TM) course and a series of monthly simulation training sessions to supplement the program and provide recently graduated nurses with a strong perioperative nursing foundation. In three years, a total of nine newly graduated RNs successfully completed the program. The three-year retention rate was 78%. (C) AORN, Inc, 2015. C1 [Byrd, Debra] VA Palo Alto Hlth Care Syst, OR Postanesthesia Care Unit, Palo Alto, CA USA. [Mullen, Linda] Ralph H Johnson VA Med Ctr, Outpatient Clin, Charleston, SC USA. [Mullen, Linda] Ralph H Johnson VA Med Ctr, Specialty Clin, Charleston, SC USA. [Renfro, David] VA Palo Alto Hlth Care Syst, Specialty Serv, Palo Alto, CA USA. [Renfro, David] VA Palo Alto Hlth Care Syst, Hosp Based Serv, Palo Alto, CA USA. [Harris, Theodore A.] VA Palo Alto Hlth Care Syst, OR, Palo Alto, CA USA. RP Byrd, D (reprint author), VA Palo Alto Hlth Care Syst, OR Postanesthesia Care Unit, Palo Alto, CA USA. OI Renfro, David/0000-0001-6405-3257; Mullen, Linda/0000-0001-9266-0134 NR 4 TC 3 Z9 3 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0001-2092 J9 ASSOC OPER ROOM NURS JI AORN J. PD SEP PY 2015 VL 102 IS 3 BP 236 EP 240 DI 10.1016/j.aorn.2015.06.015 PG 5 WC Nursing SC Nursing GA DI4FM UT WOS:000373455800008 PM 26323221 ER PT J AU Grelotti, DJ Lee, AC Fils-Aime, JR Jean, JS Therosme, T Petit-Homme, H Oswald, CM Raviola, G Eustache, E AF Grelotti, David J. Lee, Amy C. Fils-Aime, Joseph Reginald Jean, Jacques Solon Therosme, Tatiana Petit-Homme, Handy Oswald, Catherine M. Raviola, Giuseppe Eustache, Eddy TI A Pilot Initiative to Deliver Community-based Psychiatric Services in Rural Haiti After the 2010 Earthquake SO ANNALS OF GLOBAL HEALTH LA English DT Article DE Caribbean region; community-based psychiatric and neurologic care delivery; global mental health; implementation; World Health Organization Mental Health Gap Action Programme (WHO mhGAP) ID RESOURCE-LIMITED SETTINGS; MENTAL-HEALTH SURVEYS; CHALLENGES; DEPRESSION; BURDEN AB BACKGROUND Worldwide, there is a gap between the burden of mental distress and disorder and access to mental health care. This gap is particularly large in low- and middle-income countries (LMICs). After the 2010 earthquake in Haiti, the international health care organizations Partners in Health and Zanmi Lasante worked to expand local mental health services in rural Haiti. OBJECTIVE The aims of this study are to describe clinical characteristics of the patients served during a pilot project to deliver community-based psychiatric services in rural Haiti and to show how this experience complements the Mental Health Gap Action Programme ("mhGAP"), a tool developed by the World Health Organization to support mental health care delivery by nonspecialists in LMICs. METHODS The pilot was conducted in March 2011. A visiting psychiatrist traveled to rural Haiti and paired with local clinicians to evaluate patients and to support quality improvement practices in psychiatric care. Patients received a standard neuropsychiatric evaluation. mhGAP was an important clinical reference. To assess the experience, we conducted a retrospective chart review of outpatient encounters. FINDINGS Sixty-five patients presented with a wide range of common psychiatric, neurologic, and general medical conditions. Forty-nine of these patients (75%) reported primary problems subsumed by an mhGAP module. Fifteen patients (23%) reported headache as their chief complain, a condition that is not currently covered by mhGAP. Surprisingly, only 3 patients (5%), reported earthquake-related distress. CONCLUSIONS Our clinical data reinforce the need for provision of standard psychiatric and neurologic services in LMICs. Such services ought to accompany interventions targeted specifically at disaster-related problems. Clinical situations falling outside existing mhGAP modules inspired the development of supplemental treatment protocols. These observations informed coordinated efforts at Zanmi Lasante to build a sustainable, integrated mental health system in Haiti that may be relevant to other resource-limited settings. C1 [Grelotti, David J.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Grelotti, David J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Lee, Amy C.] Palo Alto Med Fdn, Mountain View, CA USA. [Fils-Aime, Joseph Reginald; Jean, Jacques Solon; Therosme, Tatiana; Petit-Homme, Handy; Eustache, Eddy] Zanmi Lasante, Port Au Prince, Haiti. [Fils-Aime, Joseph Reginald; Raviola, Giuseppe] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Oswald, Catherine M.; Raviola, Giuseppe] Partners Hlth, Boston, MA USA. [Raviola, Giuseppe] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Raviola, Giuseppe] Boston Childrens Hosp, Dept Psychiat, Boston, MA USA. RP Grelotti, DJ (reprint author), Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. EM dgrelotti@ucsd.edu OI FILS-AIME, Joseph/0000-0002-1840-8755 FU Novo Nordisk Saglik Urunleri Tic. Ltd. Sti; NIMH [T32MH017119] FX Each author has worked and/or volunteered for Partners In Health/Zanmi Lasante, the sponsor of this initiative, in support of health equity and social justice. DIG received one-time travel support for airfare in May 2014 to teach at Kocaeli University School of Medicine, Izmit, Turkey from an educational grant to Kocaeli University sponsored by Novo Nordisk Saglik Urunleri Tic. Ltd. Sti. The authors report no other potential conflicts of interest. Each author contributed substantially to this work, had a role in writing the manuscript, and had access to the data. DJG's contribution to this publication was supported by an NIMH training grant to the Harvard School of Public Health under award number T32MH017119. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIMH. The authors have no conflicts of interest to report. From the Department of Psychiatry, University of California San Diego, La Jolla, CA (DJG); Department of Psychiatry, Massachusetts General Hospital, Boston, MA (DJG); Palo Alto Medical Foundation, Mountain View, CA (ACL); Zanmi Lasante, Haiti (JRF-A, JSJ, TT, HP-H, EE); Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA (JRF-A, GR); Partners In Health, Boston, MA (CMO, GR); and the Department of Psychiatry, Harvard Medical School and Department of Psychiatry, Boston Children's Hospital, Boston, MA (GR). Address correspondence to DJG. (IDelmiGH GBH). NR 24 TC 1 Z9 1 U1 3 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2214-9996 J9 ANN GLOB HEALTH JI Ann. Glob. Health PD SEP-OCT PY 2015 VL 81 IS 5 BP 718 EP 724 DI 10.1016/j.aogh.2015.08.028 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DI0NQ UT WOS:000373193900019 PM 27036731 ER PT J AU Hess, JJ Wallenstein, J Ackerman, JD Akhter, M Ander, D Keadey, MT Capes, JP AF Hess, Jeremy J. Wallenstein, Joshua Ackerman, Jeremy D. Akhter, Murtaza Ander, Douglas Keadey, Matthew T. Capes, James P. TI Scribe Impacts on Provider Experience, Operations, and Teaching in an Academic Emergency Medicine Practice SO WESTERN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID DOCUMENTATION REQUIREMENTS; PHYSICIAN PRODUCTIVITY; PATIENT SATISFACTION AB Introduction: Physicians dedicate substantial time to documentation. Scribes are sometimes used to improve efficiency by performing documentation tasks, although their impacts have not been prospectively evaluated. Our objective was to assess a scribe program's impact on emergency department (ED) throughput, physician time utilization, and job satisfaction in a large academic emergency medicine practice. Methods: We evaluated the intervention using pre- and post-intervention surveys and administrative data. All site physicians were included. Pre- and post-intervention data were collected in four-month periods one year apart. Primary outcomes included changes in monthly average ED length of stay (LOS), provider-specific average relative value units (RVUs) per hour (raw and normalized to volume), self-reported estimates of time spent teaching, self-reported estimates of time spent documenting, and job satisfaction. We analyzed data using descriptive statistics and appropriate tests for paired pre-post differences in continuous, categorical, and ranked variables. Results: Pre- and post-survey response rates were 76.1% and 69.0%, respectively. Most responded positively to the intervention, although 9.5% reported negative impressions. There was a 36% reduction (25%-50%; p<0.01) in time spent documenting and a 30% increase (11%-46%, p<0.01) in time spent in direct patient contact. No statistically significant changes were seen in job satisfaction or perception of time spent teaching. ED volume increased by 88 patients per day (32-146, p=0.04) pre- to post-and LOS was unchanged; rates of patients leaving against medical advice dropped, and rates of patients leaving without being seen increased. RVUs per hour increased 5.5% and per patient 5.3%; both were statistically significant. No statistically significant changes were seen in patients seen per hour. There was moderate correlation between changes in ED volume and changes in productivity metrics. Conclusion: Scribes were well received in our practice. Documentation time was substantially reduced and redirected primarily to patient care. Despite an ED volume increase, LOS was maintained, with fewer patients leaving against medical advice but more leaving without being seen. RVUs per hour and per patient both increased. C1 [Hess, Jeremy J.; Wallenstein, Joshua; Ackerman, Jeremy D.; Ander, Douglas; Keadey, Matthew T.; Capes, James P.] Emory Univ, Sch Med, Dept Emergency Med, Atlanta, GA USA. [Akhter, Murtaza] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Hess, JJ (reprint author), Univ Washington, Sch Med, Emory Univ, Sch Med,Div Emergency Med,Dept Internal Med,Harbo, Box 359702,325 Ninth Ave, Seattle, WA 98104 USA. EM jjhess@uw.edu OI Ackerman, Jeremy/0000-0003-0365-0386 NR 28 TC 4 Z9 4 U1 1 U2 2 PU WESTJEM PI ORANGE PA C/O SHAHRAM LOTFIPOUR, MD, MPH, 333 CITY BLVD W STE 640, RT 128-01, ORANGE, CA 92868 USA SN 1936-900X EI 1936-9018 J9 WEST J EMERG MED JI West. J. Emerg. Med. PD SEP PY 2015 VL 16 IS 5 BP 602 EP 610 DI 10.5811/westjem.2015.6.25432 PG 9 WC Emergency Medicine SC Emergency Medicine GA DH9LP UT WOS:000373117900001 PM 26587079 ER PT J AU Sanders, JL Noble, VE Raja, AS Sullivan, AF Camargo, CA AF Sanders, Jason L. Noble, Vicki E. Raja, Ali S. Sullivan, Ashley F. Camargo, Carlos A., Jr. TI Access to and Use of Point-of-Care Ultrasound in the Emergency Department SO WESTERN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID COMPLICATIONS; MEDICINE AB Introduction: Growing evidence supports emergency physician (EP)-performed point-of-care ultrasound (PoC US). However, there is a utilization gap between academic emergency departments (ED) and other emergency settings. We elucidated barriers to PoC US use in a multistate sample of predominantly non-academic EDs to inform future strategies to increase PoC US utilization, particularly in non-academic centers. Methods: In 2010, we surveyed ED directors in five states (Arkansas, Hawaii, Minnesota, Vermont, and Wyoming; n=242 EDs) about general ED characteristics. In four states we determined barriers to PoC US use, proportion of EPs using PoC US, use privileges, and whether EPs can bill for PoC US. Results: Response rates were >80% in each state. Overall, 47% of EDs reported PoC US availability. Availability varied by state, from 34% of EDs in Arkansas to 85% in Vermont. Availability was associated with higher ED visit volume, and percent of EPs who were board certified/board eligible in emergency medicine. The greatest barriers to use were limited training (70%), expense (39%), and limited need (perceived or real) (32%). When PoC US was used by EPs, 50% used it daily, 44% had privileges not requiring radiology confirmation, and 34% could bill separately for PoC US. Only 12% of EPs used it >= 80% of the time when placing central venous lines. Conclusion: Only 47% of EDs in our five-state sample of predominantly non-academic EDs had PoC US immediately available. When available, the greatest barriers to use were limited training, expense, and limited need. Recent educational and technical advancements may help overcome these barriers. C1 [Sanders, Jason L.; Noble, Vicki E.; Raja, Ali S.; Sullivan, Ashley F.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Sanders, JL (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. EM jsanders2@partners.org NR 12 TC 4 Z9 4 U1 0 U2 0 PU WESTJEM PI ORANGE PA C/O SHAHRAM LOTFIPOUR, MD, MPH, 333 CITY BLVD W STE 640, RT 128-01, ORANGE, CA 92868 USA SN 1936-900X EI 1936-9018 J9 WEST J EMERG MED JI West. J. Emerg. Med. PD SEP PY 2015 VL 16 IS 5 BP 747 EP 752 DI 10.5811/westjem.2015.7.27216 PG 6 WC Emergency Medicine SC Emergency Medicine GA DH9LP UT WOS:000373117900023 PM 26587101 ER PT J AU Araujo, LH Amann, JM Imielinski, M Greulich, H Meyerson, M Carbone, DP AF Araujo, Luiz H. Amann, Joseph M. Imielinski, Marcin Greulich, Heidi Meyerson, Matthew Carbone, David P. TI Mutant ARAF Drives Lung Carcinogenesis Through a Distinct Oncogenic Mechanism SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE Targeted therapy; Lung neoplasms; oncogene; ARAF C1 [Araujo, Luiz H.; Amann, Joseph M.; Carbone, David P.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Imielinski, Marcin; Greulich, Heidi; Meyerson, Matthew] Broad Inst Harvard & MIT, Dana Farber Canc Inst, Boston, MA USA. [Imielinski, Marcin; Greulich, Heidi; Meyerson, Matthew] 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA MINI35.11 BP S393 EP S394 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365101397 ER PT J AU Bauer, TM Solomon, BJ Besse, B Navarro, A James, L Clancy, J Mugundu, G Martini, JF Abbattista, A Shaw, A AF Bauer, T. M. Solomon, Benjamin J. Besse, Benjamin Navarro, A. James, L. Clancy, J. Mugundu, G. Martini, J. F. Abbattista, A. Shaw, A. TI Clinical Activity and Safety of the ALK/ROS1 TK Inhibitor PF-06463922 in Advanced NSCLC SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE ALK; lung cancer; ros1; PF-06463922 C1 [Bauer, T. M.] Tennessee Oncol PLLC, Sarah Cannon Res Inst, Nashville, TN USA. [Solomon, Benjamin J.] Peter MacCallum Canc Ctr, Victoria, ACT, Australia. [Besse, Benjamin] Inst Gustave Roussy, Villejuif, France. [Navarro, A.] Vall DHebron Univ Hosp, Barcelona, Spain. [James, L.] Pfizer Oncol, New York, NY USA. [Clancy, J.] Inventiv Hlth Clin, Princeton, NJ USA. [Mugundu, G.; Martini, J. F.] Pfizer Oncol, La Jolla, CA USA. [Abbattista, A.] Pfizer Oncol, Milan, Italy. [Shaw, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 5 Z9 5 U1 3 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA ORAL33.07 BP S239 EP S239 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365100402 ER PT J AU Boyle, TA Lu, X Berry, L Ellison, KE Kowalewski, AA Rivard, CJ Khalil, F Mino-Kenudson, M Moreira, A Sholl, L Sica, G Kugler, K Kwiatkowski, DJ Varella-Garcia, M Bunn, PA Hirsch, FR AF Boyle, Theresa A. Lu, Xian Berry, Lynne Ellison, Kim E. Kowalewski, Ashley A. Rivard, Christopher J. Khalil, Farah Mino-Kenudson, Mari Moreira, Andre Sholl, Lynette Sica, Gabriel Kugler, Kelly Kwiatkowski, David J. Varella-Garcia, Marileila Bunn, Paul A., Jr. Hirsch, Fred R. TI Characterization of MET Gene and MET Protein Expression in Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE MET; Immunohistochemistry (IHC); Fluorescence in-situ hybridization (FISH); lung cancer C1 [Boyle, Theresa A.; Ellison, Kim E.; Kowalewski, Ashley A.; Rivard, Christopher J.; Varella-Garcia, Marileila; Bunn, Paul A., Jr.; Hirsch, Fred R.] Univ Colorado Denver, Div Med Oncol, Aurora, CO USA. [Lu, Xian] Univ Colorado, Sch Publ Hlth, Biostat & Informat, Denver, CO 80202 USA. [Berry, Lynne] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Khalil, Farah] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Pathol, Boston, MA 02114 USA. [Moreira, Andre] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Sholl, Lynette; Kwiatkowski, David J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Sica, Gabriel] Emory Healthcare, Atlanta, GA USA. [Kugler, Kelly] Univ Colorado Denver, Ctr Canc, Aurora, CO USA. NR 0 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA MINI13.03 BP S308 EP S308 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365101138 ER PT J AU Boyle, TA Khalil, F Mino-Kenudson, M Moreira, A Sholl, L Sica, G Knight, MZ Kowalewski, AA Ellison, K Rivard, CJ Berry, L Chen, HD Kugler, K Johnson, BE Kwiatkowski, DJ Bunn, PA Hirsch, FR AF Boyle, Theresa A. Khalil, Farah Mino-Kenudson, Mari Moreira, Andre Sholl, Lynette Sica, Gabriel Knight, Mirna Z. Kowalewski, Ashley A. Ellison, Kim Rivard, Christopher J. Berry, Lynne Chen, Heidi Kugler, Kelly Johnson, Bruce E. Kwiatkowski, David J. Bunn, Paul A., Jr. Hirsch, Fred R. TI Lung Cancer Mutation Consortium Pathologist Panel Evaluation of MET Protein SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE MET; Immunohistochemistry; standardization; lung cancer C1 [Boyle, Theresa A.; Kowalewski, Ashley A.; Ellison, Kim; Rivard, Christopher J.; Bunn, Paul A., Jr.; Hirsch, Fred R.] Univ Colorado, Div Med Oncol, Aurora, CO USA. [Khalil, Farah] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Pathol, Boston, MA 02114 USA. [Moreira, Andre] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Sholl, Lynette; Kwiatkowski, David J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Sica, Gabriel] Emory Healthcare, Atlanta, GA USA. [Knight, Mirna Z.] Metropolitan Pathologists, Lakewood, CO USA. [Berry, Lynne; Chen, Heidi] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Kugler, Kelly] Univ Colorado Denver, Ctr Canc, Aurora, CO USA. [Johnson, Bruce E.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA ORAL37.07 BP S248 EP S248 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365100426 ER PT J AU Burfeind, WR Hoo, GS Batra, R Schwarz, Y Peled, N Kaplan, T Fink, G AF Burfeind, William R., Jr. Hoo, Guy Soo Batra, Raj Schwarz, Yehuda Peled, Nir Kaplan, Tal Fink, Gershon TI Early Detection of Lung Cancer by a FISH-Based Sputum Test SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE lung cancer; Screening; Early Detection C1 [Burfeind, William R., Jr.] St Lukes Univ Hlth Network, Thorac Surg, Bethlehem, PA USA. [Hoo, Guy Soo] Los Angeles VA Med Ctr, Los Angeles, CA USA. [Batra, Raj] Los Angeles VA Med Ctr, Pulm & Crit Care, Los Angeles, CA USA. [Schwarz, Yehuda] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Pulm & Crit Care, IL-69978 Tel Aviv, Israel. [Peled, Nir] Rabin Med Ctr, Tel Aviv, Israel. [Kaplan, Tal] Bioview Ltd, Rehovot, Israel. [Fink, Gershon] Kaplan Med Ctr, Rehovot, Israel. 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA ORAL39.02 BP S251 EP S251 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365100434 ER PT J AU Camidge, DR Sequist, LV Soria, JC Wakelee, HA Ou, SH Goldman, JW Papadimitrakopoulou, V Gadgeel, S Mekhail, T Oxnard, GR Socisnki, MA Solomon, BJ Varga, A Matheny, S Despain, D Yu, H AF Camidge, D. R. Sequist, Lecia V. Soria, Jean-Charles Wakelee, Heather A. Ou, Sai-Hong Goldman, Jonathan W. Papadimitrakopoulou, Vassiliki Gadgeel, Shirish Mekhail, Tarek Oxnard, Geoffrey R. Socisnki, Mark A. Solomon, Benjamin J. Varga, Andrea Matheny, Shannon Despain, Darrin Yu, H. TI Activity of Rociletinib in EGFR Mutant NSCLC Patients with a History of CNS Involvement SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE rociletinib; EGFR; NSCLC; T790M C1 [Camidge, D. R.] Univ Colorado, Med Oncol, Denver, CO 80202 USA. [Sequist, Lecia V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Soria, Jean-Charles; Varga, Andrea] Gustave Roussy Canc Ctr, Villejuif, France. [Wakelee, Heather A.] Stanford Univ, Dept Med, Div Oncol, Stanford, CA 94305 USA. [Ou, Sai-Hong] Univ Calif Irvine, Irvine, CA USA. [Goldman, Jonathan W.] Univ Calif Los Angeles, Santa Monica, CA USA. [Papadimitrakopoulou, Vassiliki] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Gadgeel, Shirish] Karmanos Canc Inst, Detroit, MI USA. [Mekhail, Tarek] Florida Hosp Canc Insititute, Orlando, FL USA. [Oxnard, Geoffrey R.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Socisnki, Mark A.] Univ Pittsburgh, Div Hematol Oncol, Pittsburgh, PA USA. [Solomon, Benjamin J.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Matheny, Shannon] Clovis Oncol, San Francisco, CA USA. [Despain, Darrin] Clovis Oncol, Boulder, CO USA. [Yu, H.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA MINI16.04 BP S319 EP S319 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365101175 ER PT J AU Camidge, DR Starodub, AN Ocean, A Messersmith, WA Bardia, A Thomas, SS Masters, G Heist, R Maliakal, P Govindan, S Sharkey, RM Wilhelm, FE Goldenberg, DM Guarino, MJ AF Camidge, D. R. Starodub, Aleander N. Ocean, Allyson Messersmith, Wells A. Bardia, Aditya Thomas, Sajeve S. Masters, Gregory Heist, Rebecca Maliakal, Pius Govindan, Serengulam Sharkey, Robert M. Wilhelm, Francois E. Goldenberg, David M. Guarino, Michael J. TI Therapy of Advanced Metastatic Lung Cancers with an Anti-Trop-2-SN-38 Antibody-Drug Conjugate, IMMU-132: Interim Phase II Clinical Results SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE non small cell lung cancer; small cell lung cancer; antibody drug conjugate; IMMU-132 C1 [Camidge, D. R.; Messersmith, Wells A.] Univ Colorado, Ctr Canc, Denver, CO 80262 USA. [Starodub, Aleander N.] Indiana Univ, Hlth Ctr Canc Care, Goshen, IN USA. [Ocean, Allyson] Weill Cornell Med Coll, New York, NY USA. [Bardia, Aditya; Heist, Rebecca] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. [Thomas, Sajeve S.] Uf Hlth Canc Ctr Orlando Hlth, Orlando, FL USA. [Masters, Gregory; Guarino, Michael J.] Helen F Graham Canc Ctr & Res Inst, Newark, DE USA. [Maliakal, Pius; Govindan, Serengulam; Sharkey, Robert M.; Wilhelm, Francois E.; Goldenberg, David M.] Immunomedics, Clin Res, Morris Plains, NJ USA. NR 0 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA ORAL01.02 BP S173 EP S173 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365100210 ER PT J AU Camidge, R Liu, SV Powderly, J Ready, N Hodi, S Gettinger, SN Giaccone, G Liu, B Wallin, J Funke, R Waterkamp, D Heist, R AF Camidge, Ross Liu, Stephen V. Powderly, John Ready, Neal Hodi, Stephen Gettinger, Scott N. Giaccone, Giuseppe Liu, Bo Wallin, Jeffrey Funke, Roel Waterkamp, Daniel Heist, Rebecca TI Atezolizumab (MPDL3280A) Combined with Platinum-Based Chemotherapy in Non-Small Cell Lung Cancer (NSCLC): A Phase Ib Safety and Efficacy Update SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Camidge, Ross] Univ Colorado, Med Oncol, Denver, CO 80202 USA. [Liu, Stephen V.; Giaccone, Giuseppe] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. Carolina Biooncol Inst, Huntersville, NC USA. [Ready, Neal] Duke Univ, Med Ctr, Durham, NC USA. [Hodi, Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gettinger, Scott N.] Yale Canc Ctr, Med Med Oncol, New Haven, CT USA. [Liu, Bo; Wallin, Jeffrey; Funke, Roel; Waterkamp, Daniel] Genentech Inc, San Francisco, CA 94080 USA. [Heist, Rebecca] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. NR 0 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA ORAL02.07 BP S176 EP S177 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365100219 ER PT J AU Choi, PS Brooks, AN Meyerson, M AF Choi, Peter S. Brooks, Angela N. Meyerson, Matthew TI Characterization of RNA Splicing Factor Mutations in Lung Adenocarcinoma SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE RNA splicing; splice factor mutations; RBM10 C1 [Choi, Peter S.; Brooks, Angela N.; Meyerson, Matthew] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. NR 0 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA P3.04-039 BP S702 EP S702 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365103355 ER PT J AU Chong, C Ercan, D Capelletti, M Bahcall, M Sim, T Sholl, L Nishino-Habatu, M Johnson, BE Gray, N Janne, PA AF Chong, Curtis Ercan, Dalia Capelletti, Marzia Bahcall, Magda Sim, Taebo Sholl, Lynette Nishino-Habatu, Mizuki Johnson, Bruce E. Gray, Nathanael Janne, Pasi A. TI Identification of Existing Targeted Drugs That Inhibit NTRK and ROS1 in Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE Drug repurposing; cabozantinib; ros1 C1 [Chong, Curtis; Ercan, Dalia; Capelletti, Marzia; Bahcall, Magda; Sim, Taebo; Johnson, Bruce E.; Gray, Nathanael; Janne, Pasi A.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Sholl, Lynette] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Nishino-Habatu, Mizuki] Brigham & Womens Hosp, Radiol, Bosston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA PUB013 BP S765 EP S765 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365103571 ER PT J AU Chow, LQ Barlesi, F Bertino, EM Kim, DW Van Den Bent, MJ Wakelee, HA Wen, PY Arratia, PC Shen, JW Branle, F AF Chow, Laura Q. Barlesi, Fabrice Bertino, Erin M. Kim, Dong-Wan Van Den Bent, Martin J. Wakelee, Heather A. Wen, Patrick Y. Arratia, Pilar Cazorla Shen, Junwu Branle, Fabrice TI Ceritinib in ALK plus NSCLC Metastatic to Brain and/or Leptomeninges: The ASCEND-7 Study SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE Ceritinib; ALK; NSCLC; brain metastases C1 [Chow, Laura Q.] Univ Washington, Dept Med, Div Med Oncol, Seattle, WA USA. [Barlesi, Fabrice] Aix Marseille Univ, Assistance Publ Hop Marseille, Multidisciplinary Oncol & Therapeut Innovat, Marseille, France. [Bertino, Erin M.] Ohio State Univ, Columbus, OH 43210 USA. [Kim, Dong-Wan] Seoul Natl Univ Hosp, Seoul 110744, South Korea. [Van Den Bent, Martin J.] Erasmus Mc, Rotterdam, Netherlands. [Wakelee, Heather A.] Stanford Univ, Dept Med, Div Oncol, Stanford, CA 94305 USA. [Wen, Patrick Y.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Neurooncol, Boston, MA 02115 USA. [Arratia, Pilar Cazorla; Shen, Junwu] Novartis Pharmaceut, E Hanover, NJ USA. [Branle, Fabrice] Novartis Pharma Ag, Basel, Switzerland. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA P2.01-086 BP S550 EP S551 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365102484 ER PT J AU Crino, L Ahn, MJ De Marinis, F Groen, HJM Wakelee, HA Hida, T Mok, T Shaw, A Felip, E Nishio, M Scagliotti, GVV Branle, F Emeremni, C Sutradhar, S Quadrigli, M Zhang, J Spigel, D AF Crino, Lucio Ahn, Myung-Ju De Marinis, Filippo Groen, H. J. M. Wakelee, Heather A. Hida, Toyoaki Mok, Tony Shaw, Alice Felip, Enriqueta Nishio, Makoto Scagliotti, Giorgio V. V. Branle, Fabrice Emeremni, Chetachi Sutradhar, Santosh Quadrigli, Massimiliano Zhang, Jie Spigel, David TI Symptoms and QOL with Ceritinib in ALK plus NSCLC Patients with/without Brain Metastases SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE ALK Inhibitor; brain metastases; Patient-reported outcomes; Ceritinib C1 [Crino, Lucio] Perugia Hosp, Perugia, Italy. [Ahn, Myung-Ju] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. [De Marinis, Filippo] European Inst Oncol, Thorac Oncol Div, Milan, Italy. [Groen, H. J. M.] Univ Groningen, Groningen, Netherlands. [Groen, H. J. M.] Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Wakelee, Heather A.] Stanford Univ, Dept Med, Div Oncol, Stanford, CA 94305 USA. [Hida, Toyoaki] Aichi Canc Ctr, Dept Thorac Oncol, Nagoya, Aichi 464, Japan. [Mok, Tony] Chinese Univ Hong Kong, Shatin, Hong Kong, Peoples R China. [Shaw, Alice] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Felip, Enriqueta] Vall DHebron Univ Hosp, Barcelona, Spain. [Nishio, Makoto] Japanese Fdn Canc Res, Tokyo, Japan. [Scagliotti, Giorgio V. V.] Univ Turin, Turin, Italy. [Branle, Fabrice; Quadrigli, Massimiliano] Novartis Pharma AG, Basel, Switzerland. [Emeremni, Chetachi] Novartis Pharma AG, E Hanover, NJ USA. [Sutradhar, Santosh; Zhang, Jie] Novartis Pharmaceut, E Hanover, NJ USA. [Spigel, David] Tennessee Oncol, Sarah Cannon Res Inst, Nashville, TN 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA MINI31.13 BP S379 EP S379 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365101353 ER PT J AU De Rienzo, A Archer, MA Yeap, BY Dao, N Sciaranghella, D Sideris, AC Holman, AG Wang, YE Croft, L Richards, WG Bueno, R AF De Rienzo, Assunta Archer, Michael A. Yeap, Beow Y. Dao, Nhien Sciaranghella, Daniele Sideris, Antonios C. Holman, Alexander G. Wang, Yaoyu E. Croft, Larry Richards, William G. Bueno, Raphael TI Integrin Linked Kinase Pathway: A Potential Driver of Tumorigenesis of Malignant Pleural Mesothelioma SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE Mesothelioma; next-generation sequencing; Integrin Linked Kinase (ILK) Pathway; MYH9 RHOA C1 [De Rienzo, Assunta; Archer, Michael A.; Dao, Nhien; Sciaranghella, Daniele; Sideris, Antonios C.; Richards, William G.; Bueno, Raphael] Brigham & Womens Hosp, Surg, Boston, MA 02115 USA. [Yeap, Beow Y.] Massachusetts Gen Hosp, Med, Boston, MA 02114 USA. [Holman, Alexander G.; Wang, Yaoyu E.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Ctr Canc Computat Biol, Boston, MA 02115 USA. [Croft, Larry] Malaysian Genom Resource Ctr, Kuala Lumpur, Malaysia. NR 0 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA ORAL14.03 BP S200 EP S201 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365100288 ER PT J AU Do, KT Macconaill, L Dubuc, A Chen, I Chao, R Tassell, V Christensen, J Shapiro, GI Sholl, LM AF Do, Khanh T. Macconaill, Laura Dubuc, Adrian Chen, Isan Chao, Richard Tassell, Vanessa Christensen, James Shapiro, Geoffrey I. Sholl, Lynette M. TI Evaluation of the MET/AXL Receptor Tyrosine Kinase (RTK) Inhibitor MGCD265 in a Patient with Metastatic Non-Small Cell Lung Cancer (NSCLC) Harboring AXL Amplification SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Do, Khanh T.; Shapiro, Geoffrey I.] Dana Farber Canc Inst, Dept Med Oncol, Drug Dev Ctr 1Early, Boston, MA 02115 USA. [Macconaill, Laura; Dubuc, Adrian; Sholl, Lynette M.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Chen, Isan; Chao, Richard; Tassell, Vanessa; Christensen, James] Mirati Therapeut Inc, San Diego, 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA MINI30.14 BP S797 EP S797 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365103681 ER PT J AU Dwyer-Nield, LD Tennis, M Choo, KS Keith, RL Redente, EF AF Dwyer-Nield, Lori D. Tennis, Meredith Choo, Kevin S. Keith, Robert L. Redente, Elizabeth F. TI Temporal Programming of Murine Pulmonary Macrophages in N-Nitroso-Tris-(2-Chloroethyl) Urea (NTCU)-Induced Squamous Dysplasia SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE squamous dysplasia; mouse models; macrophage programming C1 [Dwyer-Nield, Lori D.] Univ Colorado Denver, Pharmaceut Sci, Aurora, CO USA. [Tennis, Meredith] Univ Colorado Denver Anschutz, Pulm, Aurora, CO USA. [Choo, Kevin S.; Keith, Robert L.] Denver Vet Affairs Med Ctr, Pulm Med, Denver, CO USA. [Redente, Elizabeth F.] Natl Jewish Hlth, Denver, CO 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA P2.04-062 BP S598 EP S598 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365102641 ER PT J AU Farago, AF Patel, M Bauer, T Liu, SV Drilon, A Wheler, J Ou, SH Jackman, DM Costa, DB Multani, P Hornby, Z Luo, D Lim, JE Iafrate, AJ Shaw, A AF Farago, Anna F. Patel, Manish Bauer, Todd Liu, Stephen V. Drilon, Alexander Wheler, Jennifer Ou, Sai-Hong Jackman, David M. Costa, Daniel B. Multani, Pratik Hornby, Zachary Luo, David Lim, Jonathan E. Iafrate, Anthony J. Shaw, Alice TI Clinical Response to Entrectinib in a Patient with NTRK1-Rearranged Non-Small Cell Lung Cancer (NSCLC) SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE Neurotrophic tyrosine kinase 1 (NTRK1); Targeted therapy; entrectinib (RXDX-101); non-small cell lung cancer C1 [Farago, Anna F.; Iafrate, Anthony J.; Shaw, Alice] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Patel, Manish] Florida Canc Specialists, Sarah Cannon Res Inst, Sarasota, FL USA. [Bauer, Todd] Tennessee Oncol PLLC, Sarah Cannon Res Inst, Nashville, TN USA. [Liu, Stephen V.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Drilon, Alexander] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Wheler, Jennifer] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Ou, Sai-Hong] Univ Calif Irvine, Irvine, CA USA. [Jackman, David M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Costa, Daniel B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol, Boston, MA 02215 USA. [Multani, Pratik; Hornby, Zachary; Luo, David; Lim, Jonathan E.] Ignyta Inc, San Diego, 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA MINI30.09 BP S374 EP S375 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365101338 ER PT J AU Flotten, O Garon, EB Arkenau, HT Hui, RN Gandhi, L Felip, E Lena, H Cappuzzo, F Horn, L Gubens, M Zhang, J Lubiniecki, G Im, E Hellmann, M AF Flotten, Oystein Garon, Edward B. Arkenau, Hendrik-Tobias Hui, Rina Gandhi, Leena Felip, Enriqueta Lena, Herve Cappuzzo, Federico Horn, Leora Gubens, Matthew Zhang, Jin Lubiniecki, Gregory Im, Ellie Hellmann, Matthew TI Pembrolizumab 2 mg/kg Q3W for Previously Treated, PD-L1-Positive Advanced NSCLC SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE pembrolizumab C1 [Flotten, Oystein] Haukeland Hosp, N-5021 Bergen, Norway. [Garon, Edward B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Arkenau, Hendrik-Tobias] Sarah Cannon Res Inst UK, London, England. [Hui, Rina] Univ Sydney, Westmead Hosp, Westmead, NSW 2145, Australia. [Gandhi, Leena] Dana Farber Canc Inst, Boston, MA 02115 USA. [Felip, Enriqueta] Vall DHebron Univ Hosp, Barcelona, Spain. [Lena, Herve] Hop Pontchaillou, Ctr Hosp Univ, Rennes, France. [Cappuzzo, Federico] Ist Toscano Tumori, Livorno, Italy. [Horn, Leora] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Gubens, Matthew] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Zhang, Jin; Lubiniecki, Gregory; Im, Ellie] Merck & Co Inc, Kenilworth, NJ USA. [Hellmann, Matthew] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RI Zhang, Jin/E-8298-2017 NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA MINI03.03 BP S270 EP S270 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365101025 ER PT J AU Gadgeel, S Gandhi, L Borghaei, H Socinski, MA Gubens, MA Stevenson, J Sequist, LV Yang, JCH Papadimitrakopoulou, V Bourque, J Bachman, RD Ge, JY Im, E Patnaik, A AF Gadgeel, Shirish Gandhi, Leena Borghaei, Hossein Socinski, Mark A. Gubens, Matthew A. Stevenson, James Sequist, Lecia V. Yang, James Chih-Hsin Papadimitrakopoulou, Vassiliki Bourque, Jennifer Bachman, Robert D. Ge, Joy Yang Im, Ellie Patnaik, Amita TI Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone as First-Line Therapy for NSCLC SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE pembrolizumab C1 [Gadgeel, Shirish] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Gandhi, Leena] Dana Farber Canc Inst, Boston, MA 02115 USA. [Borghaei, Hossein] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Socinski, Mark A.] Univ Pittsburgh, Canc Insitute, Pittsburgh, PA USA. [Gubens, Matthew A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Stevenson, James] Cleveland Clin, Cleveland, OH 44106 USA. [Sequist, Lecia V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yang, James Chih-Hsin] Natl Taiwan Univ, Taipei 10764, Taiwan. [Papadimitrakopoulou, Vassiliki] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Bourque, Jennifer; Bachman, Robert D.; Ge, Joy Yang; Im, Ellie] Merck & Co Inc, Kenilworth, NJ USA. [Patnaik, Amita] South Texas Accelerated Res Therapeut, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA P1.01-079 BP S428 EP S428 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365102079 ER PT J AU Gadgeel, S Shaw, A Govindan, R Socinski, MA Camidge, R De Petris, L Kim, DW Chiappori, A Moro-Sibilot, D Duruisseaux, M Crino, L De Pas, T Dansin, E Tessmer, A Yang, JCH Ji-Youn, H Bordogna, W Golding, S Zeaiter, A Ou, I AF Gadgeel, Shirish Shaw, A. Govindan, Ramaswamy Socinski, Mark A. Camidge, Ross De Petris, Luigi Kim, Dong-Wan Chiappori, Alberto Moro-Sibilot, Denis Duruisseaux, Michael Crino, Lucio De Pas, Tommaso Dansin, Eric Tessmer, Antje Yang, James Chih-Hsin Ji-Youn, Han Bordogna, Walter Golding, Sophie Zeaiter, Ali Ou, Ignatius TI Pooled Analysis of CNS Response to Alectinib in Two Studies of Pre-Treated ALK plus NSCLC SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE CNS metastases; Alectinib; ALK; NSCLC C1 [Gadgeel, Shirish] Karmanos Canc Ctr, Detroit, MI USA. [Shaw, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Govindan, Ramaswamy] Washington Univ, Sch Med, St Louis, MO USA. [Socinski, Mark A.] Univ Pittsburgh, Pittsburgh, PA USA. [Camidge, Ross] Univ Colorado, Ctr Canc, Denver, CO 80262 USA. [De Petris, Luigi] Karolinska Inst, Stockholm, Sweden. [Kim, Dong-Wan] Seoul Natl Univ Hosp, Seoul 110744, South Korea. [Chiappori, Alberto] H Lee Moffitt Canc Ctr & Res Inst Inc, Thorac Oncol, Tampa, FL USA. [Moro-Sibilot, Denis] Serv Pneumol, Unite Oncol Thorac, Grenoble, France. [Duruisseaux, Michael] CHU Grenoble, F-38043 Grenoble, France. [Crino, Lucio] Santa Maria Della Misericordia Hosp, Perugia, Italy. [De Pas, Tommaso] European Inst Oncol, Thorac Oncol Div, Milan, Italy. [Dansin, Eric] Ctr Oscar Lambret, F-59020 Lille, France. [Tessmer, Antje] Univ Zurich Hosp, Klin Pneumol, CH-8091 Zurich, Switzerland. [Yang, James Chih-Hsin] Natl Taiwan Univ, Grad Inst Oncol, Taipei 10764, Taiwan. [Yang, James Chih-Hsin] Natl Taiwan Univ, Canc Res Ctr, Taipei 10764, Taiwan. [Ji-Youn, Han] Natl Canc Ctr, Lung Canc Ctr, Goyang, South Korea. [Bordogna, Walter; Golding, Sophie; Zeaiter, Ali] F Hoffmann La Roche Ltd, Basel, Switzerland. [Ou, Ignatius] Univ Calif Irvine, Orange, CA 92668 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA ORAL33.05 BP S238 EP S238 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365100400 ER PT J AU Gainor, JF Marcoux, JP Rabin, M Gandhi, L Costa, DB Logan, J Jackman, DM Shaw, A AF Gainor, Justin F. Marcoux, J. P. Rabin, Michael Gandhi, Leena Costa, Daniel B. Logan, Jennifer Jackman, David M. Shaw, Alice TI A Phase II Trial of AUY922, a Heat Shock Protein 90 (HSP90) Inhibitor, in ALK-Positive Lung Cancer Patients Previously Treated with ALK Inhibitors SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE ALK; Heat shock protein 90; HSP90 C1 [Gainor, Justin F.; Logan, Jennifer; Shaw, Alice] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Marcoux, J. P.; Rabin, Michael; Gandhi, Leena; Jackman, David M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Costa, Daniel B.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA P3.01-023 BP S649 EP S649 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365103169 ER PT J AU Gettinger, SN Bazhenova, L Salgia, R Langer, CJ Gold, KA Rosell, R Shaw, A Weiss, GJ Dorer, DJ Rivera, VM Conlan, MG Kerstein, D Camidge, R AF Gettinger, Scott N. Bazhenova, Lyudmila Salgia, Ravi Langer, Corey J. Gold, Kathryn A. Rosell, Rafael Shaw, Alice Weiss, Glen J. Dorer, David J. Rivera, Victor M. Conlan, Maureen G. Kerstein, David Camidge, Ross TI Brigatinib (AP26113) Efficacy and Safety in ALK plus NSCLC: Phase 1/2 Trial Results SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE NSCLC; TKI; brigatinib C1 [Gettinger, Scott N.] Yale Canc Ctr, New Haven, CT USA. [Bazhenova, Lyudmila] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Salgia, Ravi] Univ Chicago Med, Chicago, IL USA. [Langer, Corey J.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Gold, Kathryn A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Rosell, Rafael] Dexeus Univ Inst, Barcelona, Spain. [Rosell, Rafael] Catalan Inst Oncol, Barcelona, Spain. [Shaw, Alice] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Weiss, Glen J.] Canc Treatment Ctr Amer, Goodyear, AZ USA. [Dorer, David J.; Rivera, Victor M.; Conlan, Maureen G.; Kerstein, David] Ariad Pharmaceut Inc, Cambridge, MA USA. [Camidge, Ross] Univ Colorado, Ctr Canc, Aurora, CO USA. NR 0 TC 1 Z9 1 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA ORAL33.06 BP S238 EP S239 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365100401 ER PT J AU Gitlitz, BJ Morosini, D Sable-Hunt, A Addario, BJ Jennings, MB Novello, S Vavala, T Mach, S Jones, C Oxnard, GR AF Gitlitz, Barbara J. Morosini, Deborah Sable-Hunt, Alicia Addario, Bonnie J. Jennings, Mark B. Novello, Silvia Vavala, Tiziana Mach, Stacy Jones, Carol Oxnard, Geoffrey R. TI The Genomics of Young Lung Cancer Study SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE Young Lung Cancer; Virtual Consenting; enriched population; Genomics C1 [Gitlitz, Barbara J.; Jennings, Mark B.; Jones, Carol] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Morosini, Deborah] Fdn Med, Boston, MA USA. [Sable-Hunt, Alicia; Addario, Bonnie J.] Addario Lung Canc Med Inst, San Carlos, CA USA. [Novello, Silvia; Vavala, Tiziana] Univ Turin, Turin, Italy. [Mach, Stacy; Oxnard, Geoffrey R.] Dana Farber Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA ORAL22.05 BP S793 EP S793 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365103672 ER PT J AU Gitlitz, BJ Morosini, D Sable-Hunt, A Addario, BJ Jennings, MB Novello, S Vavala, T Mach, S Jones, C Oxnard, GR AF Gitlitz, Barbara J. Morosini, Deborah Sable-Hunt, Alicia Addario, Bonnie J. Jennings, Mark B. Novello, Silvia Vavala, Tiziana Mach, Stacy Jones, Carol Oxnard, Geoffrey R. TI The Genomics of Young Lung Cancer Study SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Gitlitz, Barbara J.; Jennings, Mark B.; Jones, Carol] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Morosini, Deborah] Fdn Med, Boston, MA USA. [Sable-Hunt, Alicia; Addario, Bonnie J.] Addario Lung Canc Med Inst, San Carlos, CA USA. [Novello, Silvia; Vavala, Tiziana] Univ Turin, Turin, Italy. [Mach, Stacy; Oxnard, Geoffrey R.] Dana Farber Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA ORAL22.05 BP S217 EP S217 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365100336 ER PT J AU Goldman, JW Wakelee, HA Gadgeel, S Camidge, DR Solomon, BJ Yu, H Oxnard, GR Ou, SH Papadimitrakopoulou, V Perol, M Reckamp, K Soria, JC Varga, A Dziadziuszko, R Despain, D Matheny, S Sequist, LV AF Goldman, Jonathan W. Wakelee, Heather A. Gadgeel, Shirish Camidge, D. R. Solomon, Benjamin J. Yu, H. Oxnard, Geoffrey R. Ou, Sai-Hong Papadimitrakopoulou, Vassiliki Perol, Maurice Reckamp, Karen Soria, Jean-Charles Varga, Andrea Dziadziuszko, Rafal Despain, Darrin Matheny, Shannon Sequist, Lecia V. TI Dose Optimization of Rociletinib for EGFR Mutated NSCLC SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE EGFR; T790M; NSCLC; rociletinib C1 [Goldman, Jonathan W.] Univ Calif Los Angeles, Santa Monica, CA USA. [Wakelee, Heather A.] Stanford Univ, Stanford Canc Intitute, Med Oncol, Stanford, CA 94305 USA. [Gadgeel, Shirish] Karmanos Canc Inst, Detroit, MI USA. [Camidge, D. R.] Univ Colorado, Med Oncol, Denver, CO 80202 USA. [Solomon, Benjamin J.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Yu, H.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Oxnard, Geoffrey R.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Ou, Sai-Hong] Univ Calif Irvine, Irvine, CA USA. [Papadimitrakopoulou, Vassiliki] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Perol, Maurice] Leon Berard Canc Ctr, Dept Med Oncol, Lyon, France. [Reckamp, Karen] City Hope Natl Med Ctr, Med Oncol & Therapeut Res, Duarte, CA USA. [Soria, Jean-Charles] South Paris Univ, Villejuif, France. [Varga, Andrea] Gustave Roussy Canc Ctr, Villejuif, France. [Dziadziuszko, Rafal] Med Univ Gdansk, Gdansk, Poland. [Despain, Darrin] Clovis Oncol, Boulder, CO USA. [Matheny, Shannon] Clovis Oncol, San Francisco, CA USA. [Sequist, Lecia V.] 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA MINI16.03 BP S318 EP S319 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365101174 ER PT J AU Hammerman, P AF Hammerman, Peter TI Overview of the Histology and Potential Driver Mutations SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE Genomics; Squamous cancers; Targeted Therapies C1 [Hammerman, Peter] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA ED07.01 BP S79 EP S79 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365100030 ER PT J AU Hellmann, MD Garon, EB Gandhi, L Hui, R Zhang, J Rangwala, R Lubiniecki, G Rizvi, NA AF Hellmann, Matthew D. Garon, Edward B. Gandhi, Leena Hui, Rina Zhang, Jin Rangwala, Reshma Lubiniecki, Gregory Rizvi, Naiyer A. TI Efficacy of Pembrolizumab in Key Subgroups of Patients with Advanced NSCLC SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE pembrolizumab C1 [Hellmann, Matthew D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Garon, Edward B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Gandhi, Leena] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hui, Rina] Univ Sydney, Westmead Hosp, Westmead, NSW 2145, Australia. [Zhang, Jin; Rangwala, Reshma; Lubiniecki, Gregory] Merck & Co Inc, Kenilworth, NJ USA. [Rizvi, Naiyer A.] Columbia Univ, New York, NY USA. RI Zhang, Jin/E-8298-2017 NR 0 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA MINI03.05 BP S270 EP S270 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365101026 ER PT J AU Huynh, T Morales-Oyarvide, V Uruga, H Bozkurtlar, E Gainor, JF Hata, A Mark, E Lanuti, M Engelman, JA Mino-Kenudson, M AF Huynh, Tiffany Morales-Oyarvide, Vicente Uruga, Hironori Bozkurtlar, Emine Gainor, Justin F. Hata, Aaron Mark, Eugene Lanuti, Michael Engelman, Jeffrey A. Mino-Kenudson, Mari TI PD-L1 Expression in Lung Adenocarcinomas Correlates with KRAS Mutations and Th1/Cytotoxic T Lymphocyte Microenvironment SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE Immunotherapy; Tumor biology; lung cancer C1 [Huynh, Tiffany; Uruga, Hironori; Bozkurtlar, Emine; Mark, Eugene; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Pathol, Boston, MA 02114 USA. [Morales-Oyarvide, Vicente] Harvard Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02115 USA. [Gainor, Justin F.; Hata, Aaron] Massachusetts Gen Hosp, Canc Ctr, Boston, MA 02114 USA. [Lanuti, Michael] Massachusetts Gen Hosp, Thorac Surg, Boston, MA 02114 USA. [Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA ORAL13.01 BP S198 EP S198 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365100280 ER PT J AU Johnson, BE Kris, MG Wistuba, II Berry, L Socinski, MA Ramalingam, SS Glisson, B Otterson, G Schiller, J Cetnar, J Brahmer, JR Sequist, LV Lovly, C Minna, J Bunn, PA Kwiatkowski, DJ Kugler, K Waqar, S Politi, K Garon, EB Haura, E AF Johnson, Bruce E. Kris, Mark G. Wistuba, Ignacio I. Berry, Lynne Socinski, Mark A. Ramalingam, Suresh S. Glisson, Bonnie Otterson, Gregory Schiller, Joan Cetnar, Jeremy Brahmer, Julie R. Sequist, Lecia V. Lovly, Christine Minna, John Bunn, Paul A., Jr. Kwiatkowski, David J. Kugler, Kelly Waqar, Saiama Politi, Katerina Garon, Edward B. Haura, Eric TI Oncogenic Drivers including RET and ROS1 plus PTEN Loss and MET by IHC in Patients with Lung Adenocarcinomas: Lung Cancer Mutation Consortium 2.0 SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE next generation sequencing; Oncogenic driver; Adenocarcinoma C1 [Johnson, Bruce E.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Kris, Mark G.] Mem Sloan Kettering Canc Ctr, Thorac Oncol, New York, NY 10021 USA. [Wistuba, Ignacio I.] MD Anderson, Translat Mol Pathol, Houston, TX USA. [Berry, Lynne] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Socinski, Mark A.] Univ Pittsburgh, Pittsburgh, PA USA. [Ramalingam, Suresh S.] Emory Univ, Med Oncol, Winship Canc Inst, Atlanta, GA 30322 USA. [Glisson, Bonnie] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Otterson, Gregory] Ohio State Univ, Dept Med, Wexner Med Ctr, Columbus, OH 43210 USA. [Schiller, Joan; Minna, John] UT Southwestern, Hematol Oncol, Dallas, TX USA. [Cetnar, Jeremy] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Brahmer, Julie R.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Sequist, Lecia V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bunn, Paul A., Jr.] Univ Colorado Denver, Dept Med Oncol, Aurora, CO USA. [Kwiatkowski, David J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kugler, Kelly] Univ Colorado Denver, Ctr Canc, Aurora, CO USA. [Waqar, Saiama] Washington Univ, Internal Med Oncol, St Louis, MO USA. [Politi, Katerina] Yale Univ, Med Oncol, New Haven, CT USA. [Garon, Edward B.] UCLA, Sch Med, Santa Monica, CA USA. [Haura, Eric] Univ S Florida, H Lee Moffitt Canc Ctr, Thorac Oncol, Tampa, FL 33682 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA MINI09.06 BP S295 EP S295 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365101093 ER PT J AU Keith, RL Blatchford, PJ Jackson, MK Franklin, WA Bunn, PA Bagwell, B Merrick, DT Miller, YE AF Keith, Robert L. Blatchford, Patrick J. Jackson, Mary K. Franklin, Wilbur A. Bunn, Paul A., Jr. Bagwell, Brandi Merrick, Daniel T. Miller, York E. TI Pioglitazone for the Chemoprevention of Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE pioglitazone; chemoprevention; endobronchial dysplasia C1 [Keith, Robert L.; Miller, York E.] Denver Vet Affairs Med Ctr, Pulm Med, Denver, CO USA. [Blatchford, Patrick J.] Univ Colorado, Sch Publ Hlth, Aurora, CO USA. [Jackson, Mary K.; Bagwell, Brandi] Univ Colorado, Ctr Comprehens Canc, Aurora, CO USA. [Franklin, Wilbur A.; Merrick, Daniel T.] Univ Colorado, Pathol, Aurora, CO USA. [Bunn, Paul A., Jr.] Univ Colorado Denver, Dept Med Oncol, Aurora, CO 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA ORAL23.02 BP S218 EP S218 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365100340 ER PT J AU Keith, RL AF Keith, Robert L. TI Preclinical Models: How Good Are They? SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE murine models; lung cancer; chemoprevention C1 [Keith, Robert L.] Denver VAMC, UC Denver, Med, Denver, CO 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA MS14.01 BP S111 EP S111 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365100093 ER PT J AU Kosaka, T Endoh, H Repellin, C Tanizaki, J Ercan, D Capelletti, M Janne, PA AF Kosaka, Takayuki Endoh, Hideki Repellin, Claire Tanizaki, Junko Ercan, Dalia Capelletti, Marzia Jaenne, Pasi A. TI Secondary C805S Mutation in HER2 Gene Confers Acquired Resistance to HER2 Kinase Inhibitors in HER2 Mutant Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE HER2; NSCLC; Acquired resistance; Target therapy C1 [Kosaka, Takayuki; Endoh, Hideki; Repellin, Claire; Tanizaki, Junko; Ercan, Dalia; Capelletti, Marzia; Jaenne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA MINI09.08 BP S296 EP S296 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365101095 ER PT J AU Lacouture, ME Keefe, D Sonis, ST Giri, N Wang, T Reisman, A Sbar, E Gernhardt, D Jatoi, A AF Lacouture, Mario E. Keefe, Dorothy Sonis, Stephen T. Giri, Nagdeep Wang, Tao Reisman, Arlene Sbar, Eric Gernhardt, Diana Jatoi, Aminah TI Impact of Prophylactic Doxycycline (Doxy) on Maintaining Planned Dosing of Dacomitinib (D) an Irreversible panHER Inhibitor SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE Dacomitinib; dermatologic toxicity; doxycycline prophylaxis C1 [Lacouture, Mario E.] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA. [Keefe, Dorothy] Royal Adelaide Hosp, Adelaide, ACT, Australia. [Sonis, Stephen T.] Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. [Giri, Nagdeep] Pfizer Oncol, La Jolla, CA USA. [Wang, Tao; Gernhardt, Diana] Pfizer Oncol, Groton, CT USA. [Reisman, Arlene] Pfizer Oncol, New York, NY USA. [Sbar, Eric] Pfizer Oncol, Collegeville, PA USA. [Jatoi, Aminah] Mayo Clin, Rochester, MN USA. NR 0 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA P2.01-073 BP S546 EP S547 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365102471 ER PT J AU Leighl, N Gandhi, L Hellmann, MD Horn, L Ahn, MJ Garon, EB Hui, RN Ramalingam, SS Zhang, J Lubiniecki, G Raftopoulos, H Hamid, O AF Leighl, Natasha Gandhi, Leena Hellmann, Matthew D. Horn, Leora Ahn, Myung-Ju Garon, Edward B. Hui, Rina Ramalingam, Suresh S. Zhang, Jin Lubiniecki, Gregory Raftopoulos, Harry Hamid, Omid TI Pembrolizumab for NSCLC: Immune-Mediated Adverse Events and Corticosteroid Use SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE pembrolizumab C1 [Leighl, Natasha] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Gandhi, Leena] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hellmann, Matthew D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Horn, Leora] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Ahn, Myung-Ju] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. [Garon, Edward B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Hui, Rina] Univ Sydney, Westmead Hosp, Westmead, NSW 2145, Australia. [Ramalingam, Suresh S.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Zhang, Jin; Lubiniecki, Gregory; Raftopoulos, Harry] Merck & Co Inc, Kenilworth, NJ USA. [Hamid, Omid] Angeles Clin & Res Inst, Los Angeles, CA USA. RI Zhang, Jin/E-8298-2017 NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA ORAL31.02 BP S233 EP S233 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365100387 ER PT J AU Merrick, DT Donald, EJ Olson, D Okeefe, MC Edwards, MG Franklin, WA Dwyer-Nield, L Orlicky, D Keith, RL Miller, YE Tennis, M Baron, AE Lu, X Van Bokhoven, A Malinowski, H Bunn, PA Geraci, MW Nemenoff, R AF Merrick, Daniel T. Donald, Elizabeth J. Olson, Damon Okeefe, Mary C. Edwards, Michael G. Franklin, Wilbur A. Dwyer-Nield, Lori Orlicky, David Keith, Robert L. Miller, York E. Tennis, Meredith Baron, Anna E. Lu, Xian Van Bokhoven, Adrie Malinowski, Heather Bunn, Paul A., Jr. Geraci, Mark W. Nemenoff, Raphael TI Role of Inflammatory Infiltrates in Promoting Persistence or Regression of Bronchial Dysplasia SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE inflammation; prevention; bronchial dysplasia C1 [Merrick, Daniel T.; Donald, Elizabeth J.; Olson, Damon; Franklin, Wilbur A.; Van Bokhoven, Adrie; Malinowski, Heather] Univ Colorado, Pathol, Aurora, CO USA. [Okeefe, Mary C.] Stanford Univ, Pathol, Palo Alto, CA 94304 USA. [Edwards, Michael G.; Tennis, Meredith; Nemenoff, Raphael] Univ Colorado, Med, Aurora, CO USA. [Dwyer-Nield, Lori; Orlicky, David] Univ Colorado, Aurora, CO USA. [Keith, Robert L.; Miller, York E.] Denver Vet Affairs Med Ctr, Med, Denver, CO USA. [Baron, Anna E.; Lu, Xian] Univ Colorado, Colorado Sch Publ Hlth, Biostat & Informat, Aurora, CO USA. [Bunn, Paul A., Jr.] Univ Colorado Denver, Dept Med Oncol, Aurora, CO USA. [Geraci, Mark W.] Univ Colorado Denver, Dept Med, Aurora, CO 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA ORAL23.03 BP S218 EP S218 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365100341 ER PT J AU Meyer, M Presley, C Wilbur, D Katdare, R Hayenga, J Bell, T Liang, JM Nelson, A AF Meyer, Michael Presley, Chris Wilbur, David Katdare, Rahul Hayenga, Jon Bell, Timothy Liang, Jianming Nelson, Alan TI Blinded Evaluation of the LuCED test to Detect Early Stage Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE Early Detection; high sensitivity; high specificity; lung cancer C1 [Meyer, Michael; Presley, Chris; Katdare, Rahul; Hayenga, Jon; Bell, Timothy; Nelson, Alan] Visiongate, Phoenix, AZ 02114 USA. [Wilbur, David] Massachusetts Gen Hosp, Boston, MA USA. [Liang, Jianming] Arizona State Univ, Dept Biomed Informat, Tempe, AZ 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA MINI12.04 BP S305 EP S305 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365101127 ER PT J AU Nakachi, I Stearman, RS Edwards, M Franklin, WA Rice, JL Tan, AC Kim, J Yoo, M Fujisawa, A Betsuyaku, T Soejima, K Miller, YE Geraci, MW AF Nakachi, Ichiro Stearman, Robert S. Edwards, Michael Franklin, Wilbur A. Rice, Jessica L. Tan, Aik-Choon Kim, Jihye Yoo, Minjae Fujisawa, Akihiro Betsuyaku, Tomoko Soejima, Kenzo Miller, York E. Geraci, Mark W. TI Subtraction of Allelic Fractions (Delta-theta): A Sensitive Metric to Detect Chromosomal Alterations in Heterogeneous Premalignant Specimens SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE SNP array; bronchial dysplasia; chromosomal alteration; chemoprevention C1 [Nakachi, Ichiro] Saiseikai Utsunomiya Hosp, Dept Pulm Med, Utsunomiya, Tochigi, Japan. [Stearman, Robert S.; Edwards, Michael; Franklin, Wilbur A.; Rice, Jessica L.; Geraci, Mark W.] Univ Colorado Denver, Dept Med, Aurora, CO USA. [Tan, Aik-Choon; Kim, Jihye; Yoo, Minjae] Univ Colorado Denver AMC, Med, Aurora, CO USA. [Fujisawa, Akihiro] Kyoto Univ, Dermatol, Kyoto, Japan. [Betsuyaku, Tomoko; Soejima, Kenzo] Keio Univ, Sch Med, Pulm Med, Tokyo, Japan. [Miller, York E.] Univ Colorado, Pulm & Crit Care Med, Aurora, CO USA. [Miller, York E.] Denver Vet Affairs Med Ctr, Aurora, CO 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA MINI23.10 BP S347 EP S347 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365101258 ER PT J AU Neal, JW Dahlberg, SE Wakelee, HA Aisner, SC Bowden, M Carbone, DP Ramalingam, SS AF Neal, Joel W. Dahlberg, Suzanne E. Wakelee, Heather A. Aisner, Seena C. Bowden, Michaela Carbone, David P. Ramalingam, Suresh S. TI A Randomized Phase 2 Trial of Cabozantinib, Erlotinib or the Combination as 2nd or 3rd Line Therapy in EGFR Wild-Type NSCLC: ECOG-ACRIN E1512 SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE MET; cabozantinib; Erlotinib; wild type NSCLC C1 [Neal, Joel W.; Wakelee, Heather A.] Stanford Univ, Stanford Canc Intitute, Med Oncol, Stanford, CA 94305 USA. [Dahlberg, Suzanne E.; Bowden, Michaela] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Aisner, Seena C.] Rutgers New Jersey Med Sch, Newark, NJ USA. [Carbone, David P.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Ramalingam, Suresh S.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. NR 0 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA MINI30.04 BP S373 EP S373 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365101334 ER PT J AU Ostroff, R Delisle, K Franklin, WA Gold, L Merrick, DT Williams, S Miller, YE AF Ostroff, Rachel Delisle, Kirk Franklin, Wilbur A. Gold, Larry Merrick, Daniel T. Williams, Stephen Miller, York E. TI A New Approach to Large Scale Proteomic Profiling to Uncover Tumor Phenotypes SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE Tumor phenotype; Proteomic analysis; SOMAmer C1 [Ostroff, Rachel; Delisle, Kirk; Gold, Larry; Williams, Stephen] Somalogic Inc, Boulder, CO USA. [Franklin, Wilbur A.; Merrick, Daniel T.] Univ Colorado, Pathol, Aurora, CO USA. [Miller, York E.] Univ Colorado, Pulm & Crit Care Med, Aurora, CO USA. [Miller, York E.] Denver Vet Affairs Med Ctr, Aurora, CO 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA MINI22.10 BP S343 EP S344 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365101247 ER PT J AU Oxnard, GR AF Oxnard, Geoffrey R. TI How to Make the Best Use Of "Old" Drugs SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE EGFR; Acquired resistance C1 [Oxnard, Geoffrey R.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA ED13.03 BP S89 EP S89 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365100052 ER PT J AU Oxnard, GR Thress, K Paweletz, C Stetson, D Dougherty, B Lai, ZW Markovets, A Felip, E Vivancos, A Kuang, Y Sholl, L Redig, AJ Cantarini, M Barrett, JC Pillai, RN Cho, BC Lacroix, L Planchard, D Soria, JC Janne, PA AF Oxnard, Geoffrey R. Thress, Kenneth Paweletz, Cloud Stetson, Daniel Dougherty, Brian Lai, Zhongwu Markovets, Aleksandra Felip, Enriqueta Vivancos, Ana Kuang, Yanan Sholl, Lynette Redig, Amanda J. Cantarini, Mireille Barrett, J. Carl Pillai, Rathi N. Cho, Byoung Chul Lacroix, Ludovic Planchard, David Soria, Jean Charles Jaenne, Pasi A. TI Mechanisms of Acquired Resistance to AZD9291 in EGFR T790M Positive Lung SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE AZD9291; EGFR-TKI; T790M C1 [Oxnard, Geoffrey R.; Paweletz, Cloud; Kuang, Yanan; Redig, Amanda J.; Jaenne, Pasi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Thress, Kenneth; Stetson, Daniel; Dougherty, Brian; Lai, Zhongwu; Markovets, Aleksandra; Barrett, J. Carl] Astrazeneca, Waltham, MA USA. [Felip, Enriqueta] Vall DHebron Univ Hosp, Barcelona, Spain. [Vivancos, Ana] Vall DHebron Inst Oncol, Barcelona, Spain. [Sholl, Lynette] Brigham & Womens Hosp, Boston, MA 02115 USA. [Cantarini, Mireille] Astrazeneca, Macclesfield, Cheshire, England. [Pillai, Rathi N.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Cho, Byoung Chul] Yonsei Canc Ctr, Seoul, South Korea. [Lacroix, Ludovic; Planchard, David; Soria, Jean Charles] Gustave Roussy, Villejuif, France. NR 0 TC 3 Z9 4 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA ORAL17.07 BP S207 EP S207 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365100309 ER PT J AU Padda, SK Lara, P Gettinger, SN Engelman, JA Janne, PA West, H Zhou, LY Subramaniam, DS Leach, JW Wax, MB Neal, JW Clary, DO Goodman, LJ Wakelee, HA AF Padda, Sukhmani K. Lara, Primo, Jr. Gettinger, Scott N. Engelman, Jeffrey A. Jaenne, Pasi A. West, Howard Zhou, Lisa Y. Subramaniam, Deepa S. Leach, Joseph W. Wax, Michael B. Neal, Joel W. Clary, Douglas O. Goodman, Laurie J. Wakelee, Heather A. TI VeriStrat (R) and Epidermal Growth Factor Receptor Mutation Status in a Phase 1b/2 Study of Cabozantinib plus /- Erlotinib in Non-Small Cell Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE FISH; RT-PCR; ALK-positive lung adenocarcinoma; Ventana IHC C1 [Padda, Sukhmani K.; Zhou, Lisa Y.; Neal, Joel W.; Wakelee, Heather A.] Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA 94305 USA. [Lara, Primo, Jr.] Univ Calif Davis, Med Ctr, Sacramento, CA USA. [Gettinger, Scott N.] Yale Univ, Sch Med, New Haven, CT USA. [Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Jaenne, Pasi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [West, Howard] Swedish Canc Inst, Seattle, WA USA. [Subramaniam, Deepa S.] Georgetown Univ, Lombardi Canc Ctr, Washington, DC USA. [Leach, Joseph W.] Minnesota Onc, Minneapolis, MN USA. [Wax, Michael B.] Summit Med Grp, Berkeley Hts, NJ USA. [Clary, Douglas O.] Exelixis Inc, San Francisco, CA USA. [Goodman, Laurie J.] Biodesix, Boulder, CO 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA MINI08.04 BP S291 EP S291 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365101080 ER PT J AU Papadimitrakopoulou, V Gandara, DR Redman, M Hirsch, FR Mack, PC Borghaei, H Langer, CJ Engelman, JA Edelman, M Albain, K Lara, P Aggarwal, C Socinski, MA Sigal, EV Herbst, R AF Papadimitrakopoulou, Vassiliki Gandara, David R. Redman, Mary Hirsch, Fred R. Mack, Philip C. Borghaei, Hossein Langer, Corey J. Engelman, Jeffrey A. Edelman, Martin Albain, Kathy Lara, Primo, Jr. Aggarwal, Charu Socinski, Mark A. Sigal, Ellen V. Herbst, Roy TI Patients, Investigators and Pharmaceuticals Working Together to Accelerate Research and Access: The Lung Cancer Master Protocol (Lung-MAP) Clinical Trial SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE squamous cell cancer; Lung Cancer Master Protocol C1 [Papadimitrakopoulou, Vassiliki] UT MD Anderson Canc Ctr, Thorac Head & Neck Med Oncol, Houston, TX 95817 USA. [Gandara, David R.] Univ Calif Davis, Med Ctr, Sacramento, CA 98104 USA. [Redman, Mary] Fred Hutchinson Canc Res Ctr, Clin Res, 1124 Columbia St, Seattle, WA USA. [Hirsch, Fred R.] Univ Colorado Anschutz Med Campus, Div Med Oncol, Aurora, CO USA. [Mack, Philip C.] UC Davis Comprehens Canc Ctr, Sacramento, CA 19111 USA. [Borghaei, Hossein] Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA USA. [Langer, Corey J.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA USA. [Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 21201 USA. [Edelman, Martin] Univ Maryland, Med Ctr, Baltimore, MD 60153 USA. [Albain, Kathy] Loyola Univ, Chicago Stritch Sch Med, Dept Med, Div Hematol Oncol, Maywood, IL USA. [Lara, Primo, Jr.] UC Davis Med Ctr, Sacramento, CA 19104 USA. [Aggarwal, Charu] Univ Penn, Philadelphia, PA USA. [Socinski, Mark A.] Univ Pittsburgh, Pittsburgh, PA USA. [Sigal, Ellen V.] Friends Canc Res, Washington, DC USA. [Herbst, Roy] Yale Canc Ctr, Med Oncol, New Haven, CT 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA MTE02.01 BP S141 EP S141 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365100149 ER PT J AU Park, K Felip, E Orlov, S Yu, CJ Tsai, CM Nishio, M Dols, MC Mckeage, M Su, WC Mok, T Scagliotti, GVV Spigel, DR Zhang, J Branle, F Emeremni, C Sutradhar, S Quadrigli, M Shaw, A AF Park, Keunchil Felip, Enriqueta Orlov, Sergey Yu, Chong-Jen Tsai, Chun-Ming Nishio, Makoto Dols, Manuel Cobo Mckeage, Mark Su, Wu-Chou Mok, Tony Scagliotti, Giorgio V. V. Spigel, David R. Zhang, Jie Branle, Fabrice Emeremni, Chetachi Sutradhar, Santosh Quadrigli, Massimiliano Shaw, Alice TI PROs with Ceritinib in ALKi-Naive ALK plus NSCLC Patients with and without Brain Metastases SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE ALK Inhibitor; brain metastases; Ceritinib; Patient-reported outcomes C1 [Park, Keunchil] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. [Felip, Enriqueta] Vall DHebron Univ Hosp, Barcelona, Spain. [Orlov, Sergey] St Petersburg State Med Univ, Dept Thorac Oncol, St Petersburg, Russia. [Yu, Chong-Jen] Natl Taiwan Univ, Taipei 10764, Taiwan. [Tsai, Chun-Ming] Taipei Vet Gen Hosp, Taipei, Taiwan. [Nishio, Makoto] Japanese Fdn Canc Res, Canc Inst Hosp, Tokyo, Japan. [Dols, Manuel Cobo] Hosp Reg Univ Carlos Haya, Med Oncol Sect, Malaga, Spain. [Mckeage, Mark] Auckland City Hosp, Auckland, New Zealand. [Mckeage, Mark] Univ Auckland, Auckland 1, New Zealand. [Su, Wu-Chou] Natl Cheng Kung Univ Hosp, Tainan 70428, Taiwan. [Mok, Tony] Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. [Scagliotti, Giorgio V. V.] Univ Turin, Turin, Italy. [Spigel, David R.] Tennessee Oncol PLLC, Sarah Cannon Res Inst, Nashville, TN USA. [Zhang, Jie; Sutradhar, Santosh] Novartis Pharmaceut, E Hanover, NJ USA. [Branle, Fabrice; Emeremni, Chetachi; Quadrigli, Massimiliano] Novartis Pharma AG, Basel, Switzerland. [Shaw, Alice] 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA MINI31.14 BP S379 EP S380 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365101354 ER PT J AU Piotrowska, ZA Smit, E Costa, DB Huberman, MS Oxnard, GR Gainor, JF Heist, R Muzikansky, A Azzoli, CG Shaw, A Lin, CC Liao, WY Ho, CC Niederst, MJ Fulton, L Engelman, JA Sequist, LV Yang, JCH AF Piotrowska, Zofi A. Smit, Egbert Costa, Daniel B. Huberman, Mark S. Oxnard, Geoffrey R. Gainor, Justin F. Heist, Rebecca Muzikansky, Alona Azzoli, Christopher G. Shaw, Alice Lin, Chia-Chi Liao, Wei-Yu Ho, Chao-Chi Niederst, Matthew J. Fulton, Linnea Engelman, Jeffrey A. Sequist, Lecia V. Yang, James Chih-Hsin TI Activity of AUY922 in NSCLC Patients with EGFR Exon 20 Insertions SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE NSCLC; AUY922; EGFR; metastatic C1 [Piotrowska, Zofi A.; Gainor, Justin F.; Heist, Rebecca; Azzoli, Christopher G.; Fulton, Linnea; Engelman, Jeffrey A.; Sequist, Lecia V.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02215 USA. [Smit, Egbert] Netherlands Canc Inst, Dept Thorac Oncol, Amsterdam, Netherlands. [Costa, Daniel B.; Huberman, Mark S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol, Boston, MA 02114 USA. [Oxnard, Geoffrey R.] Dana Farber Canc, Boston, MA USA. [Muzikansky, Alona; Shaw, Alice; Niederst, Matthew J.] Massachusetts Gen Hosp, Boston, MA USA. [Lin, Chia-Chi] Natl Taiwan Univ Hosp, Dept Oncol, Taipei 100, Taiwan. [Liao, Wei-Yu; Yang, James Chih-Hsin] Natl Taiwan Univ Hosp, Taipei, Taiwan. [Ho, Chao-Chi] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei, Taiwan. 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA MINI30.06 BP S373 EP S374 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365101335 ER PT J AU Ramalingam, SS O'Byrne, KJ Mok, T Boyer, M Janne, PA Goldberg, Z Mather, CB Taylor, I Zhang, H Paz-Ares, L AF Ramalingam, Suresh S. O'Byrne, Kenneth J. Mok, Tony Boyer, Michael Jaenne, Pasi A. Goldberg, Zelanna Mather, Cecile B. Taylor, Ian Zhang, Hui Paz-Ares, Luis TI Comparison of the Efficacy of Dacomitinib v Erlotinib for NSCLC Pts with Del 19/L858R SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE EGFR activating mutations; Dacomitinib; Erlotinib C1 [Ramalingam, Suresh S.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [O'Byrne, Kenneth J.] Princess Alexandra Hosp, Brisbane, Qld 4102, Australia. [Mok, Tony] Chinese Univ Hong Kong, Prince Wales Hosp, Hong Kong, Hong Kong, Peoples R China. [Boyer, Michael] Chris OBrien Lifehouse, Camperdown, NSW, Australia. [Jaenne, Pasi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Goldberg, Zelanna; Mather, Cecile B.; Taylor, Ian; Zhang, Hui] Pfizer Oncol, New York, NY USA. [Paz-Ares, Luis] Hosp Univ Virgen Del Rocio, Seville, Spain. RI IBIS, NUEVAS TERAPIA/P-3415-2015 NR 0 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA MINI05.08 BP S278 EP S278 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365101049 ER PT J AU Ramalingam, SS Yang, JCH Lee, C Kurata, T Kim, DW John, T Nogami, N Ohe, Y Rukazenkov, Y Frewer, P Cantarini, M Ghiorghiu, S Janne, PA AF Ramalingam, Suresh S. Yang, James Chih-Hsin Lee, Chee Kurata, Takayasu Kim, Dong-Wan John, Thomas Nogami, Naoyuki Ohe, Yuichiro Rukazenkov, Yuri Frewer, Paul Cantarini, Mireille Ghiorghiu, Serban Jaenne, Pasi A. TI AZD9291 in Treatment-Naive EGFRm Advanced NSCLC: AURA First-Line Cohort SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE AZD9291; EGFR-TKI; T790M C1 [Ramalingam, Suresh S.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Yang, James Chih-Hsin] Natl Taiwan Univ Hosp, Taipei, Taiwan. [Lee, Chee] St George Hosp, Sydney, NSW, Australia. [Kurata, Takayasu] Kansai Med Univ, Hirakata Hosp, Osaka, Japan. [Kim, Dong-Wan] Seoul Natl Univ Hosp, Seoul 110744, South Korea. [John, Thomas] Austin Hlth, Olivia Newton John Canc Ctr, Melbourne, Vic, Australia. [Nogami, Naoyuki] Natl Hosp Org, Shikoku Canc Ctr, Matsuyama, Ehime, Japan. [Ohe, Yuichiro] Natl Canc Ctr, Tokyo, Japan. [Rukazenkov, Yuri; Frewer, Paul; Cantarini, Mireille] Astrazeneca, Macclesfield, Cheshire, England. [Ghiorghiu, Serban] Astrazeneca, Cambridge, England. [Jaenne, Pasi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA MINI16.07 BP S319 EP S320 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365101177 ER PT J AU Reckamp, K Brahmer, JR Spigel, DR Rizvi, NA Poddubskaya, E West, H Eberhardt, WEE Baas, P Antonia, SJ Pluzanski, A Vokes, E Holgado, E Waterhouse, D Ready, N Gainor, JF Frontera, OA Horn, L Paz-Ares, L Li, A Lynch, M AF Reckamp, Karen Brahmer, Julie R. Spigel, David R. Rizvi, Naiyer A. Poddubskaya, Elena West, Howard Eberhardt, Wilfried E. E. Baas, Paul Antonia, Scott J. Pluzanski, Adam Vokes, Everett Holgado, Esther Waterhouse, David Ready, Neal Gainor, Justin F. Aren Frontera, Osvaldo Horn, Leora Paz-Ares, Luis Li, Ang Lynch, Mark TI Phase 3, Randomized Trial (CheckMate 017) of Nivolumab (NIVO) vs Docetaxel in Advanced Squamous (SQ) Cell Non-Small Cell Lung Cancer (NSCLC) SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE Nivolumab; PD-L1; Squamous cell NSCLC; Immunotherapy C1 [Reckamp, Karen] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Brahmer, Julie R.] Sidney Kimmel Comprehens Canc Ctr John Hopkins, Baltimore, MD USA. [Spigel, David R.] Tennessee Oncol PLLC, Sarah Cannon Res Inst, Nashville, TN USA. [Rizvi, Naiyer A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Poddubskaya, Elena] NN Blokhin Russian Canc Res Ctr, Moscow, Russia. [West, Howard] Swedish Canc Inst, Seattle, WA USA. [Eberhardt, Wilfried E. E.] Univ Duisburg Essen, Ruhrlandklin, West German Canc Ctr, Univ Hosp Essen, Essen, Germany. [Baas, Paul] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands. [Antonia, Scott J.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Pluzanski, Adam] Inst Marii Sklodowskiej Curie, Ctr Onkol, Warsaw, Poland. [Vokes, Everett] Univ Chicago Med & Biol Sci, Chicago, IL USA. [Holgado, Esther] Hosp Madrid, Norte Sanchinarro, Spain. [Waterhouse, David] Oncol Hematol Care, Cincinnati, OH USA. [Ready, Neal] Duke Univ, Med Ctr, Durham, NC USA. [Gainor, Justin F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Aren Frontera, Osvaldo] Ctr Int Estudios Clin, Santiago, Chile. [Horn, Leora] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Paz-Ares, Luis] Hosp Univ Virgen del Rocio, Seville, Spain. [Li, Ang] Bristol Myers Squibb Co, Global Biometr Sci Stat Programming & Technol, Princeton, NJ USA. [Lynch, Mark] Bristol Myers Squibb Co, Princeton, NJ USA. RI IBIS, NUEVAS TERAPIA/P-3415-2015 NR 0 TC 2 Z9 2 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA ORAL02.01 BP S174 EP S175 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365100214 ER PT J AU Sacher, AG Paweletz, C Alden, R O'Connell, A Lim, L Raymond, C Janne, PA Oxnard, GR AF Sacher, Adrian G. Paweletz, Cloud Alden, Ryan O'Connell, Allison Lim, Lee Raymond, Chris Janne, Pasi A. Oxnard, Geoffrey R. TI A Prospective Study of Rapid Plasma Genotyping Utilizing Sequential ddPCR and NGS in Newly Diagnosed Advanced NSCLC Patients SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE Genomics; Targeted therapy; NSCLC; Biomarkers C1 [Sacher, Adrian G.; Alden, Ryan; Janne, Pasi A.; Oxnard, Geoffrey R.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Paweletz, Cloud; O'Connell, Allison] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA USA. [Lim, Lee; Raymond, Chris] Resolut Bio, Cambridge, MA USA. RI Sacher, Adrian/I-8080-2016 OI Sacher, Adrian/0000-0001-7865-2701 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA ORAL38.01 BP S248 EP S248 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365100427 ER PT J AU Shaw, A Loong, H Tan, DSW Griscti, K Gao, HT Finckenstein, F Scott, J Vansteenkiste, J AF Shaw, Alice Loong, Herbert Tan, Daniel S. -W. Griscti, Kerry Gao, Haitao Finckenstein, Friedrich Scott, Jeffrey Vansteenkiste, Johan TI A Multicenter Phase 1B Study of Ceritinib plus Nivolumab in Patients with ALK plus NSCLC SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE Ceritinib; Nivolumab; ALK; NSCLC C1 [Shaw, Alice] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Loong, Herbert] Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. [Tan, Daniel S. -W.] Natl Canc Ctr, Singapore, Singapore. [Griscti, Kerry; Gao, Haitao; Scott, Jeffrey] Novartis Pharrna, E Hanover, NJ USA. [Finckenstein, Friedrich] Bristol Myers Squibb Co, Princeton, NJ USA. [Vansteenkiste, Johan] Univ Hosp Ku Leuven, Leuven, Belgium. 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA P1.01-085 BP S430 EP S430 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365102085 ER PT J AU Shaw, A West, H Socinski, MA Ou, I Gandhi, L Gadgeel, S Belani, CP Shirai, K Bazhenova, L Santos, E Riely, GJ Chiappori, A Cetnar, J Mekhail, T Chao, B Borghaei, H Gold, KA Johannsdottir, H Ruf, T Boisserie, F Henschel, V Zeaiter, A Camidge, R AF Shaw, Alice West, Howard Socinski, Mark A. Ou, Ignatius Gandhi, Leena Gadgeel, Shirish Belani, Chandra P. Shirai, Keisuke Bazhenova, Lyudmila Santos, Edgardo Riely, Gregory J. Chiappori, Alberto Cetnar, Jeremy Mekhail, Tarek Chao, Bo Borghaei, Hossein Gold, Kathryn A. Johannsdottir, Hrefna Ruf, Thorsten Boisserie, Frederic Henschel, Volkmar Zeaiter, Ali Camidge, Ross TI Updated Efficacy/Safety Data From the Phase 2 NP28761 Study of Alectinib in ALK plus NSCLC SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE Alectinib; ALK; NSCLC C1 [Shaw, Alice] Massachusetts Gen Hosp, Boston, MA 02114 USA. [West, Howard] Swedish Canc Inst, Seattle, WA USA. [Socinski, Mark A.] Univ Pittsburgh, Pittsburgh, PA USA. [Ou, Ignatius] Univ Calif Irvine, Orange, CA 92668 USA. [Gandhi, Leena] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gadgeel, Shirish] Wayne State Univ, Detroit, MI USA. [Belani, Chandra P.] Penn State Hershey Canc Inst, Hershey, PA USA. [Shirai, Keisuke] Med Univ S Carolina, Charleston, SC 29425 USA. [Bazhenova, Lyudmila] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Santos, Edgardo] Florida Atlantic Univ, Lynn Canc Inst, Oncol, Boca Raton, FL 33431 USA. [Riely, Gregory J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Chiappori, Alberto] H Lee Moffitt Canc Ctr & Res Inst Inc, Thorac Oncol, Tampa, FL USA. [Cetnar, Jeremy] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Mekhail, Tarek] Florida Hosp Canc Insititute, Orlando, FL USA. [Chao, Bo] Ohio State Univ, Internal Med, Columbus, OH 43210 USA. [Borghaei, Hossein] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Gold, Kathryn A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Johannsdottir, Hrefna; Ruf, Thorsten; Boisserie, Frederic; Henschel, Volkmar; Zeaiter, Ali] F Hoffmann La Roche Ltd, Basel, Switzerland. [Camidge, Ross] Univ Colorado, Med, Denver, CO 80202 USA. NR 0 TC 1 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA ORAL33.03 BP S237 EP S238 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365100399 ER PT J AU Spigel, DR Shan, J Chiappori, A Keilholz, U Reck, M Edelman, M Domine, M Park, K Jang, TW Su, WC Sanborn, RE Horn, L Heist, R Mainwaring, P Gerber, DE AF Spigel, David R. Shan, Joseph Chiappori, Alberto Keilholz, Ulrich Reck, Martin Edelman, Martin Domine, Manuel Park, Keunchil Jang, Tae Won Su, Wu-Chou Sanborn, Rachel E. Horn, Leora Heist, Rebecca Mainwaring, Paul Gerber, David E. TI Phase III, Randomized, Double-Blind Trial of Bavituximab Plus Docetaxel in Previously Treated Stage IIIb/IV Non-Squamous NSCLC (SUNRISE) SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE Non-small-cell lung cancer; Bavituximab; Immunotherapy; phosphatidylserine C1 [Spigel, David R.] Tennessee Oncol Pllc, Sarah Cannon Res Inst, Nashville, TN USA. [Shan, Joseph] Peregrine Pharmaceut Inc, Tustin, CA USA. [Chiappori, Alberto] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Thorac Oncol, Tampa, FL 33612 USA. [Keilholz, Ulrich] Charite, D-13353 Berlin, Germany. [Reck, Martin] Lungclin Grosshansdorf, Grosshansdorf, Germany. [Edelman, Martin] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. [Domine, Manuel] Hosp Univ Fdn Jimenez Diaz, Oncol, Madrid, Spain. [Park, Keunchil] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. [Jang, Tae Won] Kosin Univ, Coll Med, Pusan, South Korea. [Su, Wu-Chou] Natl Cheng Kung Univ Hosp, Taipei, Taiwan. [Sanborn, Rachel E.] Providence Portland Med Ctr, Med Oncol, Portland, OR USA. [Horn, Leora] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Heist, Rebecca] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Mainwaring, Paul] Icon Canc Fdn, Milton, Australia. [Gerber, David E.] UT Southwestern, Dallas, TX USA. NR 0 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA P1.01-075 BP S427 EP S427 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365102075 ER PT J AU Sundaresan, T AF Sundaresan, Tilak TI Circulating Tumor Cells SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE Circulating tumor cells; Circulating Tumor DNA; EGFR; T790M C1 [Sundaresan, Tilak] Massachusetts Gen Hosp, MGH Canc Ctr, Div Hematol Oncol, 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA MS02.02 BP S93 EP S93 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365100057 ER PT J AU Thress, K Leeson, J Geradts, J Schuler, M Ahn, MJ Wolf, J Gold, KA Yang, JCH Blackhall, F Su, WC Jacobs, V Smith, NR Angell, H Brown, K Vishwanathan, K Barrett, JC Cantarini, M Janne, PA AF Thress, Kenneth Leeson, James Geradts, Joseph Schuler, Martin Ahn, Myung-Ju Wolf, Juergen Gold, Kathryn A. Yang, James Chih-Hsin Blackhall, Fiona Su, Wu-Chou Jacobs, Vivien Smith, Neil R. Angell, Helen Brown, Kathryn Vishwanathan, Karthick Barrett, J. Carl Cantarini, Mireille Jaenne, Pasi A. TI Design, Execution, and Preliminary Biomarker Results from Paired Tumor Biopsy Cohorts of the AZD9291 AURA Trial SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE AZD9291; EGFR-TKI C1 [Thress, Kenneth; Vishwanathan, Karthick; Barrett, J. Carl] Astrazeneca, Waltham, MA USA. [Leeson, James; Jacobs, Vivien; Smith, Neil R.; Brown, Kathryn; Cantarini, Mireille] Astrazeneca, Macclesfield, Cheshire, England. [Geradts, Joseph; Angell, Helen] Astrazeneca, Cambridge, England. [Schuler, Martin] Univ Hosp Essen, West German Canc Ctr, Essen, Germany. [Ahn, Myung-Ju] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. [Wolf, Juergen] Univ Cologne, Ctr Integrated Oncol, D-50931 Cologne, Germany. [Gold, Kathryn A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Yang, James Chih-Hsin] Natl Taiwan Univ Hosp, Taipei, Taiwan. [Blackhall, Fiona] Univ Manchester, Manchester, Lancs, England. [Blackhall, Fiona] Christie NHS Fdn Trust, Manchester, Lancs, England. [Su, Wu-Chou] Natl Cheng Kung Univ Hosp, Tainan 70428, Taiwan. [Jaenne, Pasi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA MINI16.09 BP S320 EP S320 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365101179 ER PT J AU Uruga, H Bozkurtlar, E Huynh, T Muzikansky, A Hata, A Gainor, JF Mark, E Engelman, JA Lanuti, M Mino-Kenudson, M AF Uruga, Hironori Bozkurtlar, Emine Huynh, Tiffany Muzikansky, Alona Hata, Aaron Gainor, Justin F. Mark, Eugene Engelman, Jeffrey A. Lanuti, Michael Mino-Kenudson, Mari TI Programmed Cell Death Ligand (PD-L1) Expression in Stage II and III Lung Adenocarcinomas and Nodal Metastases SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE PD-L1; lung adenocarcinoma; Adjuvant therapy; lymph node C1 [Uruga, Hironori; Bozkurtlar, Emine; Huynh, Tiffany; Mark, Eugene; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Pathol, Boston, MA 02114 USA. [Muzikansky, Alona; Hata, Aaron; Gainor, Justin F.; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Lanuti, Michael] Massachusetts Gen Hosp, Thorac Surg, 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA MINI02.02 BP S266 EP S266 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365101013 ER PT J AU Wakelee, HA Dahlberg, SE Keller, SM Tester, WJ Gandara, DR Graziano, SL Adjei, A Leighl, N Aisner, SC Rothman, JM Patel, J Sborov, MD Mcdermott, SR Perez-Soler, R Traynor, AM Butts, C Evans, T Horn, L Ramalingam, SS Schiller, J AF Wakelee, Heather A. Dahlberg, Suzanne E. Keller, Steven M. Tester, William J. Gandara, David R. Graziano, Stephen L. Adjei, Alex Leighl, Natasha Aisner, Seena C. Rothman, Jan M. Patel, Jyoti Sborov, Mark D. Mcdermott, Sean R. Perez-Soler, Roman Traynor, Anne M. Butts, Charles Evans, Tracey Horn, Leora Ramalingam, Suresh S. Schiller, Joan TI Randomized Phase III Trial of Adjuvant Chemotherapy with or without Bevacizumab in Resected Non-Small Cell Lung Cancer (NSCLC): Results of E1505 SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE adjuvant chemotherapy; bevacizumab; early stage NSCLC C1 [Wakelee, Heather A.] Stanford Univ, Med Oncol, Stanford Canc Intitute, Stanford, CA 94305 USA. [Dahlberg, Suzanne E.] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Keller, Steven M.] Montefiore Med Ctr, Cardiovasc & Thorac Surg, Bronx, NY 10467 USA. [Tester, William J.] Albert Einstein Med Ctr, Philadelphia, PA 19141 USA. [Gandara, David R.] Univ Calif Davis, Ctr Comprehens Canc, Sacramento, CA 95817 USA. [Graziano, Stephen L.] SUNY Upstate Med Univ, Med Oncol, Syracuse, NY 13210 USA. [Adjei, Alex] Roswell Pk Canc Inst, Med, Buffalo, NY 14263 USA. [Leighl, Natasha] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Aisner, Seena C.] Rutgers New Jersey Med Sch, Newark, NJ USA. [Rothman, Jan M.] Reg Canc Ctr, Erie, PA USA. [Patel, Jyoti] Northwestern Univ, Chicago, IL 60611 USA. [Sborov, Mark D.] Edina Clin, Edina, PA USA. [Mcdermott, Sean R.] Adelaide & Meath Hosp, Med Oncol, Dublin, Ireland. [Perez-Soler, Roman] Montefiore Med Ctr, Oncol, Bronx, NY 10467 USA. [Traynor, Anne M.] Univ Wisconsin, Madison, WI USA. [Butts, Charles] Univ Alberta, Div Oncol, Edmonton, AB, Canada. [Evans, Tracey] Univ Penn, Philadelphia, PA 19104 USA. [Horn, Leora] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Ramalingam, Suresh S.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Schiller, Joan] UT Southwestern, Hematol Oncol, Dallas, TX USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA PLEN04.03 BP S796 EP S796 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365103677 ER PT J AU Wakelee, HA Sequist, LV Gadgeel, S Soria, JC Goldman, JW Yu, H Camidge, DR Solomon, BJ Matheny, S Despain, D Papadimitrakopoulou, V AF Wakelee, Heather A. Sequist, Lecia V. Gadgeel, Shirish Soria, Jean-Charles Goldman, Jonathan W. Yu, H. Camidge, D. R. Solomon, Benjamin J. Matheny, Shannon Despain, Darrin Papadimitrakopoulou, Vassiliki TI Rociletinib in NSCLC Patients with Negative Central Testing for T790M in TIGER-X SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE rociletinib; NSCLC; EGFR; T790M C1 [Wakelee, Heather A.] Stanford Univ, Dept Med, Div Oncol, Stanford, CA 94305 USA. [Sequist, Lecia V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gadgeel, Shirish] Karmanos Canc Inst, Detroit, MI USA. [Soria, Jean-Charles] Gustave Roussy Canc Ctr, Villejuif, France. [Goldman, Jonathan W.] Univ Calif Los Angeles, Santa Monica, CA USA. [Yu, H.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Camidge, D. R.] Univ Colorado, Med Oncol, Denver, CO 80202 USA. [Solomon, Benjamin J.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Matheny, Shannon] Clovis Oncol, San Francisco, CA USA. [Despain, Darrin] Clovis Oncol, Boulder, CO USA. [Papadimitrakopoulou, Vassiliki] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA MINI03.10 BP S271 EP S272 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365101030 ER PT J AU Wakelee, HA Dahlberg, SE Keller, SM Tester, WJ Gandara, DR Graziano, SL Adjei, A Leighl, N Aisner, SC Rothman, JM Patel, J Sborov, MD Mcdermott, SR Perez-Soler, R Traynor, AM Butts, C Evans, T Horn, L Ramalingam, SS Schiller, J AF Wakelee, Heather A. Dahlberg, Suzanne E. Keller, Steven M. Tester, William J. Gandara, David R. Graziano, Stephen L. Adjei, Alex Leighl, Natasha Aisner, Seena C. Rothman, Jan M. Patel, Jyoti Sborov, Mark D. Mcdermott, Sean R. Perez-Soler, Roman Traynor, Anne M. Butts, Charles Evans, Tracey Horn, Leora Ramalingam, Suresh S. Schiller, Joan TI Randomized Phase III Trial of Adjuvant Chemotherapy with or without Bevacizumab in Resected Non-Small Cell Lung Cancer (NSCLC): Results of E1505 SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Wakelee, Heather A.] Stanford Univ, Stanford Canc Inst, Med Oncol, Stanford, CA 94305 USA. [Dahlberg, Suzanne E.] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Keller, Steven M.] Montefiore Med Ctr, Cardiovasc & Thorac Surg, Bronx, NY 10467 USA. [Tester, William J.] Albert Einstein Med Ctr, Philadelphia, PA 19141 USA. [Gandara, David R.] Univ Calif Davis, Ctr Comprehens Canc, Sacramento, CA USA. [Graziano, Stephen L.] SUNY Upstate Med Univ, Med Oncol, Syracuse, NY 13210 USA. [Adjei, Alex] Roswell Pk Canc Inst, Med, Buffalo, NY 14263 USA. [Leighl, Natasha] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Aisner, Seena C.] Rutgers New Jersey Med Sch, Newark, NJ USA. [Rothman, Jan M.] Reg Canc Ctr, Erie, PA USA. [Patel, Jyoti] Northwestern Univ, Chicago, IL 60611 USA. [Sborov, Mark D.] Edina Clin, Edina, MN USA. [Mcdermott, Sean R.] Adelaide & Meath Hosp, Med Oncol, Dublin, Ireland. [Perez-Soler, Roman] Montefiore Med Ctr, Oncol, Bronx, NY 10467 USA. [Traynor, Anne M.] Univ Wisconsin, Madison, WI USA. [Butts, Charles] Univ Alberta, Div Oncol, Edmonton, AB, Canada. [Evans, Tracey] Univ Penn, Philadelphia, PA 19104 USA. [Horn, Leora] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Ramalingam, Suresh S.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Schiller, Joan] UT Southwestern, Hematol Oncol, Dallas, TX USA. NR 0 TC 1 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA PLEN04.03 BP S66 EP S66 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365100003 ER PT J AU Wiesner, G Ashworth, R Heng, JC Rainville, I Mcreynolds, K Sable-Hunt, A Garber, J Carbone, DP Oxnard, GR AF Wiesner, Georgia Ashworth, Renee Heng, Jennifer C. Rainville, Irene Mcreynolds, Katharine Sable-Hunt, Alicia Garber, Judy Carbone, David P. Oxnard, Geoffrey R. TI Spectrum of Cancer Types in Kindreds with NSCLC and EGFR T790M Mutations: Results from INHERIT EGFR SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE EGFR; familial lung cancer; NSCLC; T790M C1 [Wiesner, Georgia; Ashworth, Renee; Mcreynolds, Katharine] Vanderbilt Ingram Canc Ctr, Genet Med, Nashville, TN USA. [Heng, Jennifer C.; Rainville, Irene; Garber, Judy; Oxnard, Geoffrey R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sable-Hunt, Alicia] Addario Lung Canc Med Inst, San Carlos, CA USA. [Carbone, David P.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA ORAL22.02 BP S216 EP S216 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365100334 ER PT J AU Yang, JCH Ahn, MJ Ramalingam, SS Sequist, LV Novello, S Su, WC Hirashima, T Kim, DW Lawrance, R Cantarini, M Ghiorghiu, S Janne, PA AF Yang, James Chih-Hsin Ahn, Myung-Ju Ramalingam, Suresh S. Sequist, Lecia V. Novello, Silvia Su, Wu-Chou Hirashima, Tomonori Kim, Dong-Wan Lawrance, Rachael Cantarini, Mireille Ghiorghiu, Serban Jaenne, Pasi A. TI AZD9291 in Pre-Treated T790M Positive Advanced NSCLC: AURA Study Phase II Extension Cohort SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE AZD9291; EGFR-TKI; T790M C1 [Yang, James Chih-Hsin] Natl Taiwan Univ Hosp, Taipei, Taiwan. [Ahn, Myung-Ju] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. [Ramalingam, Suresh S.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Sequist, Lecia V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Novello, Silvia] Univ Turin, Dept Oncol, Turin, Italy. [Su, Wu-Chou] Natl Cheng Kung Univ Hosp, Tainan 70428, Taiwan. [Hirashima, Tomonori] Osaka Prefectural Med Ctr Resp & Allerg Dis, Osaka, Japan. [Kim, Dong-Wan] Seoul Natl Univ Hosp, Seoul 110744, South Korea. [Lawrance, Rachael; Cantarini, Mireille] Astrazeneca, Macclesfield, Cheshire, England. [Ghiorghiu, Serban] Astrazeneca, Cambridge, England. [Jaenne, Pasi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 5 Z9 5 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA MINI16.06 BP S319 EP S319 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365101176 ER PT J AU Zhou, HYY Wu, CC Mino-Kenudson, M Tapias, LF Lanuti, M AF Zhou, Haiyu Y. Wu, Carol C. Mino-Kenudson, Mari Tapias, Luis F. Lanuti, Michael TI Driver Mutation Status in Resected Stage I Lung Adenocarcinoma: Correlation with Radiographic CT Findings SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE KRAS; Ground glass opacity; non small cell lung cancer; EGFR C1 [Zhou, Haiyu Y.] Guangdong Gen Hosp, Thorac Surg, Guangzhou, Guangdong, Peoples R China. [Wu, Carol C.] Univ Texas MD Anderson Canc Ctr, Radiol, Houston, TX 77030 USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Pathol, Boston, MA 02114 USA. [Tapias, Luis F.; Lanuti, Michael] Massachusetts Gen Hosp, Thorac Surg, 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2015 VL 10 IS 9 SU 2 MA MINI08.13 BP S293 EP S294 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DE1CX UT WOS:000370365101088 ER PT J AU Magerl, M Bernstein, JA Banerji, A Li, HH Lumry, WR Maurer, M Riedl, M Chen, H Schranz, J AF Magerl, M. Bernstein, J. A. Banerji, A. Li, H. H. Lumry, W. R. Maurer, M. Riedl, M. Chen, H. Schranz, J. TI Response to subcutaneous human C1-Inhibitor for the prevention of angioedema attacks in patients with hereditary angioedema: subgroups based on prior intravenous C1-inhibitor use SO ALLERGY LA English DT Meeting Abstract CT Congress of the European-Academy-of-Allergy-and-Clinical-Immunology CY JUN 06-10, 2015 CL Barcelona, SPAIN SP European Acad Allergy & Clin Immunol C1 [Magerl, M.; Maurer, M.] Charite, D-13353 Berlin, Germany. [Bernstein, J. A.] Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. [Banerji, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Li, H. H.] Inst Asthma & Allergy, Chevy Chase, MD USA. [Lumry, W. R.] AARA Res Ctr, Dallas, TX USA. [Riedl, M.] Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. [Chen, H.; Schranz, J.] Shire, Wayne, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD SEP PY 2015 VL 70 SU 101 SI SI MA 120 BP 60 EP 60 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DD5GM UT WOS:000369950700121 ER PT J AU Ruiter, B Patil, SU Shreffler, WG AF Ruiter, B. Patil, S. U. Shreffler, W. G. TI Vitamins A and D have antagonistic effects on expression of effector cytokines and gut-homing integrin in human innate lymphoid cells SO ALLERGY LA English DT Meeting Abstract CT Congress of the European-Academy-of-Allergy-and-Clinical-Immunology CY JUN 06-10, 2015 CL Barcelona, SPAIN SP European Acad Allergy & Clin Immunol C1 [Ruiter, B.; Patil, S. U.; Shreffler, W. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ruiter, B.; Patil, S. U.; Shreffler, W. G.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD SEP PY 2015 VL 70 SU 101 SI SI MA 149 BP 73 EP 73 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DD5GM UT WOS:000369950700148 ER PT J AU Patil, S Steinbrecher, J Ogunniyi, A Calatroni, A Moon, J Love, JC Shreffler, W AF Patil, S. Steinbrecher, J. Ogunniyi, A. Calatroni, A. Moon, J. Love, J. C. Shreffler, W. TI Clonal homology in immunoglobulin heavy chains in unrelated patients undergoing peanut oral immunotherapy SO ALLERGY LA English DT Meeting Abstract CT Congress of the European-Academy-of-Allergy-and-Clinical-Immunology CY JUN 06-10, 2015 CL Barcelona, SPAIN SP European Acad Allergy & Clin Immunol C1 [Patil, S.; Steinbrecher, J.; Moon, J.; Shreffler, W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ogunniyi, A.; Love, J. C.] MIT, Cambridge, MA 02139 USA. [Calatroni, A.] Rho Inc, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD SEP PY 2015 VL 70 SU 101 SI SI MA 169 BP 83 EP 83 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DD5GM UT WOS:000369950700166 ER PT J AU Harrow, B Sedaghat, AR Munzel, U Tarr, A Gever, L Hofmeister, J Dufour, R AF Harrow, B. Sedaghat, A. R. Munzel, U. Tarr, A. Gever, L. Hofmeister, J. Dufour, R. TI Health-care costs of asthma are lower using MP29-02*vs sequential sprays for allergic rhinitis SO ALLERGY LA English DT Meeting Abstract CT Congress of the European-Academy-of-Allergy-and-Clinical-Immunology CY JUN 06-10, 2015 CL Barcelona, SPAIN SP European Acad Allergy & Clin Immunol C1 [Harrow, B.] Meda, Hlth Econ & Outcomes Res, Somerset, NJ USA. [Sedaghat, A. R.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Sedaghat, A. R.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Munzel, U.] Meda, Corp Clinical Affairs, Bad Homburg, Germany. [Tarr, A.; Dufour, R.] Comprehens Hlth Insights Inc, Louisville, KY USA. [Gever, L.; Hofmeister, J.] Meda, Somerset, NJ 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 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD SEP PY 2015 VL 70 SU 101 SI SI MA 1231 BP 501 EP 501 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DD5GM UT WOS:000369950702560 ER PT J AU Hoffmire, CA Kemp, JE Bossarte, RM AF Hoffmire, Claire A. Kemp, Janet E. Bossarte, Robert M. TI Changes in Suicide Mortality for Veterans and Nonveterans by Gender and History of VHA Service Use, 2000-2010 SO PSYCHIATRIC SERVICES LA English DT Article ID ADVERSE CHILDHOOD EXPERIENCES; DEATH REPORTING SYSTEM; TRAUMATIC BRAIN-INJURY; 16 STATES; RISK; AFGHANISTAN; IRAQ; INDIVIDUALS; INCREASE; RATES AB Objective: Veterans are believed to be at high risk of suicide. However, research comparing suicide rates between veterans and nonveterans is limited, and even less is known regarding differences by history of Veterans Health Administration (VHA) service use. This study directly compared veteran and nonveteran suicide risk while for the first time differentiating veterans by VHA service use. Methods: The cross-sectional study analyzed data from 173,969 adult suicide decedents from 23 states (2000-2010) included in the U.S. Department of Veterans Affairs suicide data archive. Annual standardized mortality ratios (SMRs) were computed for veterans compared with nonveterans and for veterans who used VHA services compared with veterans who did not, overall and separately for males and females. Results: After the analysis controlled for age and gender differences, the number of observed veteran suicides was approximately 20% higher than expected in 2000 (SMR=1.19, 95% confidence interval [CI]=1.10-1.28), and this increased to 60% higher by 2010 (SMR=1.63, CI=1.58-1.68). The elevated risk for female veterans (2010 SMR=5.89) was higher than that observed for male veterans (2010 SMR=1.54). Trends for non-VHA-utilizing veterans mirrored those of the veteran population as a whole, and the SMR for VHA-utilizing veterans declined. Since 2003, the number of suicides among VHA-utilizing veterans was less than expected when compared directly with the suicide rate among non-VHA-utilizing veterans. Conclusions: Veterans are members of the community and, as such, are an important part of observed increases in U.S. suicide rates. Not all veterans are at equal or increasing risk of suicide, however. VHA-utilizing veterans appear to have declining absolute and relative suicide rates. C1 [Hoffmire, Claire A.; Kemp, Janet E.] US Dept Vet Affairs, Ctr Excellence Suicide Prevent VISN2, Canandaigua, NY USA. [Bossarte, Robert M.] US Dept Vet Affairs, Off Publ Hlth, Washington, DC USA. [Hoffmire, Claire A.; Bossarte, Robert M.] Univ Rochester, Dept Psychiat, Rochester, NY USA. RP Hoffmire, CA (reprint author), US Dept Vet Affairs, Ctr Excellence Suicide Prevent VISN2, Canandaigua, NY USA. EM claire.hoffmire@va.gov NR 33 TC 13 Z9 13 U1 0 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD SEP PY 2015 VL 66 IS 9 BP 959 EP 965 DI 10.1176/appi.ps.201400031 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA DE6EB UT WOS:000370725400016 PM 25930036 ER PT J AU Sripada, RK Richards, SKH Rauch, SAM Walters, HM Ganoczy, D Bohnert, KM Gorman, LA Kees, M Blow, AJ Valenstein, M AF Sripada, Rebecca K. Richards, Sarah K. H. Rauch, Sheila A. M. Walters, Heather M. Ganoczy, Dara Bohnert, Kipling M. Gorman, Lisa A. Kees, Michelle Blow, Adrian J. Valenstein, Marcia TI Socioeconomic Status and Mental Health Service Use Among National Guard Soldiers SO PSYCHIATRIC SERVICES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; TREATMENT-SEEKING; UNITED-STATES; CARE; PSYCHOTHERAPY; VETERANS; BARRIERS; IRAQ AB Objective: Convergent evidence suggests that low socioeconomic status (SES) may be related to reduced mental health service use. However, this relationship has not been tested in the National Guard (NG) population, in which the prevalence of mental health symptoms is high. Methods: Surveys were completed by 1,262 NG soldiers. SES was measured by education and income. Adjusted multivariable regression models assessed associations between SES, overall service use, and use of specific types of services. Results: SES was not associated with overall use but was associated with use of certain types of services. Higher SES was associated with lower likelihood of psychotropic medication use (odds ratio=.83, 95% confidence interval=.72-.96), and higher SES strengthened the positive relationship between PTSD and use of individual therapy. Conclusions: Higher SES may increase the use of individual therapy among soldiers with PTSD. Barriers to care among individuals with low SES merit continued attention and outreach efforts. C1 [Sripada, Rebecca K.; Walters, Heather M.; Ganoczy, Dara; Bohnert, Kipling M.; Valenstein, Marcia] Ann Arbor Hlth Care Syst, US Dept Vet Affairs, Serious Mental Illness Treatment Resource & Evalu, Ctr Clin Management Res, Ann Arbor, MI USA. [Richards, Sarah K. H.; Rauch, Sheila A. M.] Ann Arbor Hlth Care Syst, US Dept Vet Affairs, Mental Hlth Serv, Ann Arbor, MI USA. [Sripada, Rebecca K.; Walters, Heather M.; Bohnert, Kipling M.; Kees, Michelle; Valenstein, Marcia] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA. [Gorman, Lisa A.] Michigan Publ Hlth Inst, Okemos, MI 48864 USA. [Blow, Adrian J.] Michigan State Univ, Dept Family & Child Ecol, E Lansing, MI 48824 USA. RP Sripada, RK (reprint author), Ann Arbor Hlth Care Syst, US Dept Vet Affairs, Serious Mental Illness Treatment Resource & Evalu, Ctr Clin Management Res, Ann Arbor, MI USA. EM rekaufma@umich.edu OI Sripada, Rebecca/0000-0002-2844-3458 FU VA Health Services Research and Development (HSRD) [RRP 09-420, SDP 10-047]; Welcome Back Veterans Initiative; McCormick Foundation, Families and Communities Together Coalition of Michigan State University; VA Advanced Fellowship Program in Mental Illness Research and Treatment; VA Serious Mental Illness Treatment Resource and Evaluation Center; Mental Health Service of the VA Ann Arbor Healthcare System; VA HSRD [CDA 11-245] FX This work was supported by VA Health Services Research and Development (HSR&D) grants RRP 09-420 and SDP 10-047, the Welcome Back Veterans Initiative, the McCormick Foundation, Families and Communities Together Coalition of Michigan State University, the VA Advanced Fellowship Program in Mental Illness Research and Treatment, the VA Serious Mental Illness Treatment Resource and Evaluation Center, and the Mental Health Service of the VA Ann Arbor Healthcare System. Dr. Bohnert is supported by VA HSR&D grant CDA 11-245. NR 15 TC 0 Z9 0 U1 1 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD SEP PY 2015 VL 66 IS 9 BP 992 EP 995 DI 10.1176/appi.ps.201400346 PG 4 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA DE6EB UT WOS:000370725400022 PM 25930042 ER PT J AU Sakadzic, S AF Sakadzic, Sava TI Measuring microscopic flow patterns and brain oxygenation SO ACTA PHYSIOLOGICA LA English DT Meeting Abstract C1 [Sakadzic, Sava] Massachusetts Gen Hosp, Opt Div, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Sakadzic, Sava] Harvard Univ, Sch Med, Charlestown, 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 1748-1708 EI 1748-1716 J9 ACTA PHYSIOL JI Acta Physiol. PD SEP PY 2015 VL 215 SU 706 SI SI MA 14:3 BP 63 EP 63 PG 1 WC Physiology SC Physiology GA DE3KB UT WOS:000370526500074 ER PT J AU Orechia, J Pathak, A Shi, YL Nawani, A Belozerov, A Fontes, C Lakhiani, C Jawale, C Patel, C Quinn, D Botvinnik, D Mei, E Cotter, E Byleckie, J Ullman-Cullere, M Chhetri, P Chalasani, P Karnam, P Beaudoin, R Sahu, S Belozerova, Y Mathew, JP AF Orechia, John Pathak, Ameet Shi, Yunling Nawani, Aniket Belozerov, Andrey Fontes, Caitlin Lakhiani, Camille Jawale, Chetan Patel, Chetansharan Quinn, Daniel Botvinnik, Dmitry Mei, Eddie Cotter, Elizabeth Byleckie, James Ullman-Cullere, Mollie Chhetri, Padam Chalasani, Poornima Karnam, Purushotham Beaudoin, Ronald Sahu, Sandeep Belozerova, Yelena Mathew, Jomol P. TI OncDRS: An integrative clinical and genomic data platform for enabling translational research and precision medicine SO APPLIED AND TRANSLATIONAL GENOMICS LA English DT Article DE Genomic profile; Clinical & genomic data integration; Next generation sequencing data; Precision medicine; Clinical and translational informatics ID CANCER MEDICINE; TUMOR SAMPLES AB We live in the genomic era of medicine, where a patient's genomic/molecular data is becoming increasingly important for disease diagnosis, identification of targeted therapy, and risk assessment for adverse reactions. However, decoding the genomic test results and integrating it with clinical data for retrospective studies and cohort identification for prospective clinical trials is still a challenging task. In order to overcome these barriers, we developed an overarching enterprise informatics framework for translational research and personalized medicine called Synergistic Patient and Research Knowledge Systems (SPARKS) and a suite of tools called Oncology Data Retrieval Systems (OncDRS). OncDRS enables seamless data integration, secure and self-navigated query and extraction of clinical and genomic data from heterogeneous sources. Within a year of release, the system has facilitated more than 1500 research queries and has delivered data for more than 50 research studies. (C) 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). C1 [Orechia, John; Pathak, Ameet; Shi, Yunling; Nawani, Aniket; Belozerov, Andrey; Fontes, Caitlin; Lakhiani, Camille; Jawale, Chetan; Patel, Chetansharan; Quinn, Daniel; Botvinnik, Dmitry; Mei, Eddie; Cotter, Elizabeth; Byleckie, James; Ullman-Cullere, Mollie; Chhetri, Padam; Chalasani, Poornima; Karnam, Purushotham; Beaudoin, Ronald; Sahu, Sandeep; Belozerova, Yelena; Mathew, Jomol P.] Dana Faber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. RP Mathew, JP (reprint author), Univ Massachusetts, Sch Med, 55 Lake Ave North, Worcester, MA 01655 USA. EM jomol.mathew@umassmed.edu NR 22 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2212-0661 J9 APPL TRANSL GENOM JI Appl. Transl. Genomics PD SEP PY 2015 VL 6 BP 18 EP 25 DI 10.1016/j.atg.2015.08.005 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA DD9SW UT WOS:000370266900006 PM 27054074 ER PT J AU Zerillo, JA Stuver, SO Fraile, B Dodek, AD Jacobson, JO AF Zerillo, Jessica A. Stuver, Sherri O. Fraile, Belen Dodek, Anton D. Jacobson, Joseph O. TI Understanding Oral Chemotherapy Prescribing Patterns at the End of Life at a Comprehensive Cancer Center: Analysis of a Massachusetts Payer Claims Database SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Article ID CELL LUNG-CANCER; OF-LIFE; ACQUIRED-RESISTANCE; PALLIATIVE CARE; QUALITY; PATIENT; DISCONTINUATION; CAPECITABINE; INDICATORS; DESIGN AB Purpose: Receipt of chemotherapy in the last 14 days of life is a measure of potential overuse of care. Specific measures defining appropriate end-of-life use of oral agents have not yet been described, and little is known about prescribing patterns. Methods: We conducted an exploratory analysis of 371 patients at Dana-Farber Cancer Institute who were covered by the Blue Cross Blue Shield of Massachusetts pharmacy benefit and died during 2012 to 2013. We analyzed processed claims as a surrogate for chemotherapy administration. We compared oral with parenteral chemotherapy claims in the last 6 months of life. Results: In the last 6 months of life, 294 patients (79%) had chemotherapy claims, including 81 (22%) prescribed an oral agent; 20 patients had claims for oral chemotherapy in the last 30 days of life. For eight patients (40%), this was the initial start of that oral agent. In the last 14 days of life, only 23 patients had chemotherapy claims, including six patients prescribed an oral agent. Conclusion: The collection of oral chemotherapy use data through insurance claims was feasible. Processed claims for chemotherapy, including oral, sharply declined during the last 30 days of life, consistent with a shift to palliative management. These results highlight the need for a more comprehensive analysis of oral chemotherapy prescribing patterns and development of specific measures to define the appropriate use of oral chemotherapy at the end of life. C1 Dana Farber Canc Inst, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. Blue Cross & Blue Shield Massachusetts, Boston, MA USA. RP Zerillo, JA (reprint author), Dana Farber Canc Inst, Dept Qual & Patient Safety, 450 Brookline Ave,LW225, Boston, MA 02215 USA. EM jzerillo@partners.org NR 26 TC 1 Z9 1 U1 3 U2 3 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 SEP PY 2015 VL 11 IS 5 BP 372 EP + DI 10.1200/JOP.2015.003921 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DE4ZG UT WOS:000370638800006 PM 26243650 ER PT J AU Grande, D Asch, DA Wan, F Bradbury, AR Jagsi, R Mitra, N AF Grande, David Asch, David A. Wan, Fei Bradbury, Angela R. Jagsi, Reshma Mitra, Nandita TI Are Patients With Cancer Less Willing to Share Their Health Information? Privacy, Sensitivity, and Social Purpose SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Article ID CONJOINT-ANALYSIS; CARE-SYSTEM; ATTITUDES; DISCRIMINATION; PERCEPTIONS; CONSENT AB Purpose: Growing use of electronic health information increases opportunities to build population cancer databases for research and care delivery. Understanding patient views on reuse of health information is essential to shape privacy policies and build trust in these initiatives. Methods: We randomly assigned nationally representative participants (N = 3,336) with and without prior cancer to six of 18 scenarios describing different uses of electronic health information. The scenarios varied the user, use, and sensitivity of the information. Participants rated each scenario on a scale of 1 to 10 assessing their willingness to share their electronic health information. We used conjoint analysis to measure the relative importance of each attribute (ie, use, user, and sensitivity). Results: Participants with and without a prior diagnosis of cancer had a similar willingness to share health information (0.27; P = .42). Both cancer and noncancer participants rated the purpose of information use as the most important factor (importance weights, 67.1% and 45.6%, respectively). For cancer participants, the sensitivity of the information was more important (importance weights, 29.8% v 1.2%). However, cancer participants were more willing to share their health information when the information included more sensitive genetic information (0.48; P = .015). Cancer and noncancer respondents rated uses and users similarly. Conclusion: The information sharing preferences of participants with and without a prior diagnosis of cancer were driven mainly by the purpose of information reuse. Although conventional thinking suggests patients with cancer might be less willing to share their health information, we found participants with cancer were more willing to share their inherited genetic information. C1 Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Michigan, Sch Med, Ann Arbor, MI USA. RP Grande, D (reprint author), 3641 Locust Walk,Colonial Penn Ctr 407, Philadelphia, PA 19014 USA. EM dgrande@wharton.upenn.edu FU NCI NIH HHS [P30 CA016520]; NHGRI NIH HHS [5R21HG006047-02, R21 HG006047] NR 28 TC 1 Z9 1 U1 0 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 SEP PY 2015 VL 11 IS 5 BP 378 EP + DI 10.1200/JOP.2015.004820 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DE4ZG UT WOS:000370638800007 PM 26265174 ER PT J AU Wang, F Gordon, BA Ryman, DC Ma, SM Xiong, CJ Hassenstab, J Goate, A Fagan, AM Cairns, NJ Marcus, DS McDade, E Ringman, JM Graff-Radford, NR Ghetti, B Farlow, MR Sperling, R Salloway, S Schofield, PR Masters, CL Martins, RN Rossor, MN Jucker, M Danek, A Forster, S Lane, CAS Morris, JC Benzinger, TLS Bateman, RJ AF Wang, Fen Gordon, Brian A. Ryman, Davis C. Ma, Shengmei Xiong, Chengjie Hassenstab, Jason Goate, Alison Fagan, Anne M. Cairns, Nigel J. Marcus, Daniel S. McDade, Eric Ringman, John M. Graff-Radford, Neill R. Ghetti, Bernardino Farlow, Martin R. Sperling, Reisa Salloway, Steve Schofield, Peter R. Masters, Colin L. Martins, Ralph N. Rossor, Martin N. Jucker, Mathias Danek, Adrian Foerster, Stefan Lane, Christopher A. S. Morris, John C. Benzinger, Tammie L. S. Bateman, Randall J. CA Dominantly Inherited Alzheimer Net TI Cerebral amyloidosis associated with cognitive decline in autosomal dominant Alzheimer disease SO NEUROLOGY LA English DT Article ID HEALTHY OLDER-ADULTS; A-BETA; EPISODIC MEMORY; DEPOSITION; IMPAIRMENT; BRAIN; METAANALYSIS; INDIVIDUALS; BIOMARKERS; DEMENTIA AB Objective: To investigate the associations of cerebral amyloidosis with concurrent cognitive performance and with longitudinal cognitive decline in asymptomatic and symptomatic stages of autosomal dominant Alzheimer disease (ADAD). Methods: Two hundred sixty-three participants enrolled in the Dominantly Inherited Alzheimer Network observational study underwent neuropsychological evaluation as well as PET scans with Pittsburgh compound B. One hundred twenty-one participants completed at least 1 follow-up neuropsychological evaluation. Four composite cognitive measures representing global cognition, episodic memory, language, and working memory were generated using z scores from a battery of 13 standard neuropsychological tests. General linear mixed-effects models were used to investigate the relationship between baseline cerebral amyloidosis and baseline cognitive performance and whether baseline cerebral amyloidosis predicts cognitive change over time (mean follow-up 2.32 years +/- 0.92, range 0.89-4.19) after controlling for estimated years from expected symptom onset, APOE epsilon 4 allelic status, and education. Results: In asymptomatic mutation carriers, amyloid burden was not associated with baseline cognitive functioning but was significantly predictive of longitudinal decline in episodic memory. In symptomatic mutation carriers, cerebral amyloidosis was correlated with worse baseline performance in multiple cognitive composites and predicted greater decline over time in global cognition, working memory, and Mini-Mental State Examination. Conclusions: Cerebral amyloidosis predicts longitudinal episodic memory decline in presymptomatic ADAD and multidomain cognitive decline in symptomatic ADAD. These findings imply that amyloidosis in the brain is an indicator of early cognitive decline and provides a useful outcome measure for early assessment and prevention treatment trials. C1 [Wang, Fen; Ryman, Davis C.; Ma, Shengmei; Fagan, Anne M.; Cairns, Nigel J.; Morris, John C.; Bateman, Randall J.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Gordon, Brian A.; Marcus, Daniel S.; Benzinger, Tammie L. S.] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. [Xiong, Chengjie] Washington Univ, Sch Med, Dept Biostat, St Louis, MO USA. [Hassenstab, Jason] Washington Univ, Sch Med, Dept Psychol, St Louis, MO USA. [Benzinger, Tammie L. S.] Washington Univ, Sch Med, Dept Neurol Surg, St Louis, MO USA. [Goate, Alison] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [McDade, Eric] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Ringman, John M.] Univ Calif Los Angeles, Mary S Easton Ctr Alzheimers Dis Res, Los Angeles, CA USA. [Graff-Radford, Neill R.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Ghetti, Bernardino] Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA. [Farlow, Martin R.] Indiana Univ Sch Med, Dept Neurol, Indianapolis, IN 46202 USA. [Sperling, Reisa] Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. [Sperling, Reisa] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Salloway, Steve] Brown Univ, Butler Hosp, Dept Neurol, Providence, RI 02912 USA. [Salloway, Steve] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Schofield, Peter R.] Neurosci Res Australia, Sydney, NSW, Australia. [Schofield, Peter R.] Univ New S Wales, Sydney, NSW, Australia. [Masters, Colin L.] Univ Melbourne, Mental Hlth Res Inst, Parkville, Vic 3052, Australia. [Martins, Ralph N.] Edith Cowan Univ, Sch Exercise Biomed & Hlth Sci, Ctr Excellence Alzheimers Dis Res & Care, Perth, WA, Australia. [Rossor, Martin N.; Lane, Christopher A. S.] UCL Inst Neurol, Dementia Res Ctr, London, England. [Jucker, Mathias] German Ctr Neurodegenerat Dis, Tubingen, Germany. [Jucker, Mathias] Hertie Inst Clin Brain Res, Tubingen, Germany. [Danek, Adrian] Univ Munich, Neurol Klin, Munich, Germany. [Foerster, Stefan] Tech Univ Munich, Klinikum Rechts Isar, Nukl Med Klin & Poliklin, German Ctr Neurodegenerat Dis, D-80290 Munich, Germany. [Foerster, Stefan] Tech Univ Munich, Klinikum Rechts Isar, TUM Neuroimaging Ctr, D-80290 Munich, Germany. [Wang, Fen] Capital Med Univ, Xuan Wu Hosp, Dept Neurol, Beijing, Peoples R China. RP Benzinger, TLS (reprint author), Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. EM benzingert@mir.wustl.edu; batemanr@wustl.edu RI Danek, Adrian/G-7339-2011; OI Danek, Adrian/0000-0001-8857-5383; Gordon, Brian/0000-0003-2109-2955 FU NIA [U19 AG032438]; JO & JR Wicking Trust [13026, 20821]; NIH [U-01-AG042791]; Alzheimer's Association; DIAN Pharma Consortium (Biogen); DIAN Pharma Consortium (Eisai); DIAN Pharma Consortium (Elan); DIAN Pharma Consortium (Eli Lilly); DIAN Pharma Consortium (Forum); DIAN Pharma Consortium (Genentech); DIAN Pharma Consortium (Hoffman La-Roche); DIAN Pharma Consortium (Janssen); DIAN Pharma Consortium (Mithridion); DIAN Pharma Consortium (Novartis); DIAN Pharma Consortium (Pfizer); DIAN Pharma Consortium (Sanofi-Aventis); Chinese Health and Family Planning Committee; National Natural Science Foundation of China [81100797] FX The DIAN is supported by NIA grant U19 AG032438 to J.C. Morris and by the generous support of F. Simmons and O. Mohan and an anonymous foundation, in addition to DIAN site support from the German Center for Neurodegenerative Diseases (DZNE), the NIHR Queen Square Dementia Biomedical Research Unit, and JO & JR Wicking Trust grants 13026 & 20821. The DIAN-TU (R.J. Bateman, PI) is supported by funding from the NIH U-01-AG042791, Alzheimer's Association, and the DIAN Pharma Consortium (Biogen, Eisai, Elan, Eli Lilly, Forum, Genentech, Hoffman La-Roche, Janssen, Mithridion, Novartis, Pfizer, and Sanofi-Aventis). The authors acknowledge Chinese Society of Neurology, the National Key Department of Neurology funded by Chinese Health and Family Planning Committee, and the National Natural Science Foundation of China (81100797) for their support for this study. NR 40 TC 5 Z9 5 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD SEP 1 PY 2015 VL 85 IS 9 BP 790 EP 798 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA DE3CL UT WOS:000370504300012 PM 26245925 ER PT J AU Kraemer, JD Siedner, MJ Stoto, MA AF Kraemer, John D. Siedner, Mark J. Stoto, Michael A. TI ANALYZING VARIABILITY IN EBOLA-RELATED CONTROLS APPLIED TO RETURNED TRAVELERS IN THE UNITED STATES SO HEALTH SECURITY LA English DT Article ID HEALTH EMERGENCY PREPAREDNESS; PUBLIC-HEALTH; QUALITY IMPROVEMENT; PANDEMIC INFLUENZA; FEDERAL PREEMPTION; AIR-TRAVEL; 2009 H1N1; LAW; LESSONS; ENTRY AB Public health authorities have adopted entry screening and subsequent restrictions on travelers from Ebola-affected West African countries as a strategy to prevent importation of Ebola virus disease (EVD) cases. We analyzed international, federal, and state policies-principally based on the policy documents themselves and media reports-to evaluate policy variability. We employed means-ends fit analysis to elucidate policy objectives. We found substantial variation in the specific approaches favored by WHO, CDC, and various American states. Several US states impose compulsory quarantine on a broader range of travelers or require more extensive monitoring than recommended by CDC or WHO. Observed differences likely partially resulted from different actors having different policy goals-particularly the federal government having to balance foreign policy objectives less salient to states. Further, some state-level variation appears to be motivated by short-term political goals. We propose recommendations to improve future policies, which include the following: (1) actors should explicitly clarify their objectives, (2) legal authority should be modernized and clarified, and (3) the federal government should consider preempting state approaches that imperil its goals. C1 [Kraemer, John D.; Stoto, Michael A.] Georgetown Univ, Dept Hlth Syst Adm, 231 St Marys Hall,3700 Reservoir Rd, Washington, DC USA. [Kraemer, John D.; Stoto, Michael A.] Georgetown Univ, ONeill Inst Natl & Global Hlth Law, 231 St Marys Hall,3700 Reservoir Rd, Washington, DC USA. [Siedner, Mark J.] Harvard Univ, Sch Med, Ctr Global Hlth, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Kraemer, JD (reprint author), Georgetown Univ, Dept Hlth Syst Adm, 231 St Marys Hall,3700 Reservoir Rd, Washington, DC USA.; Kraemer, JD (reprint author), Georgetown Univ, ONeill Inst Natl & Global Hlth Law, 231 St Marys Hall,3700 Reservoir Rd, Washington, DC USA. EM jdk32@georgetown.edu FU US Centers for Disease Control and Prevention grant (Preparedness and Emergency Response Research Center) [5P01TP000307-01]; National Institutes of Health [K23 MH09916] FX This manuscript was developed with funding support awarded to Harvard School of Public Health under cooperative agreements with the US Centers for Disease Control and Prevention grant 5P01TP000307-01 (Preparedness and Emergency Response Research Center). MJS receives research support from the National Institutes of Health (K23 MH09916). NR 107 TC 3 Z9 3 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2326-5094 EI 2326-5108 J9 HEALTH SECUR JI Health Secur. PD SEP-OCT PY 2015 VL 13 IS 5 BP 295 EP 306 DI 10.1089/hs.2015.0016 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DD1OQ UT WOS:000369691400001 PM 26348222 ER PT J AU Papavasileiou, E Zygoura, V Richardson, T Cortis, D Eleftheriadis, H Jackson, TL AF Papavasileiou, Evangelia Zygoura, Vasiliki Richardson, Theresa Cortis, Dominic Eleftheriadis, Haralabos Jackson, Timothy L. TI Intravitreal aflibercept (A-IVI) for the treatment of neovascular age related macular degeneration (nv-AMD): one year experience SO HELLENIC JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE Aflibercept; Intravitreal; Neovascular age; Related macular degeneration ID TRAP-EYE; RANIBIZUMAB; PREVALENCE AB Objective: To report the anatomical and functional results of intravitreal injections of aflibercept (Eylea) (A-IVI) for the treatment of naive eyes with neovascular age-related macular degeneration (nv-AMD). Subjects and Methods: This retrospective, one center, non-comparative chart review included 26 treatment naive eyes with nv-AMD of 26 patients (14 male) with a mean age of 80.5 (range 63-91) who had a complete follow-up of 14 months. The morphological analysis included spectral domain optical coherence tomography and fundus fluorescein angiography, while the functional assessment included logarithm of the minimum angle of resolution (LogMAR) best correct visual acuity (BCVA). The timing of the follow-up was: baseline, 3, 6, and 14 months. All patients received 8 A-IVI according to the protocol (first 3 consecutive monthly A-IVI, followed by bi-monthly retreatment for the first year, regardless of disease activity as per local guidelines). Statistical analysis was performed using ANOVA. Improvement of visual acuity more than 15 letters was considered as 'improvement', less than 5 letters as 'stable' and any letter loss as 'worsening'. Results: Mean standard deviation LogMAR visual acuity improved from 0.26 +/- 0.15 at presentation to 0.14 +/- 0.20 at the final follow-up of 14 months (P=0.02). BCVA was stable in 23.1%, improved in 61.5% (16 eyes) worsened in 15.4%. A mean pretreatment central macular thickness of 409 mu m reduced significantly to 229 mu m at month 14 (P<0.02). The OCT of eyes with worsened BCVA showed resolution of retinal fluid but presence of subretinal fibrosis. No adverse events were attributed to aflibercept. Conclusions: Patients who had a worsening in visual acuity were found to have longer duration of symptoms prior to treatment and presence of geographic atrophy, and/or subretinal haemorrhage and/or subretinal fibrosis at baseline. From our experience, with 14 months follow-up, A-IVI is an effective treatment for treatment naive patients with nv-AMD. Our real world results were similar to pivotal trials. C1 [Papavasileiou, Evangelia] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Papavasileiou, Evangelia; Eleftheriadis, Haralabos; Jackson, Timothy L.] Kings Coll Hosp London, London, England. [Zygoura, Vasiliki] Moorfields Eye Hosp, London, England. [Richardson, Theresa] Imperial Coll Healthcare NHS Trust, Western Eye Hosp, London, England. [Cortis, Dominic] Univ Leicester, Dept Math, Leicester LE1 7RH, Leics, England. [Jackson, Timothy L.] Kings Coll London, London WC2R 2LS, England. RP Papavasileiou, E (reprint author), Kings Coll Hosp London, Dept Ophthalmol, Denmark Hill, London SE5 9RS, England. EM liapapava@hotmail.com NR 16 TC 0 Z9 0 U1 0 U2 0 PU HELLENIC SOC NUCLEAR MEDICINE PI THESSALONIKI PA 51 HERMU ST, THESSALONIKI, 546 23, GREECE SN 1790-5427 J9 HELL J NUCL MED JI Hell. J. Nucl. Med. PD SEP-DEC PY 2015 VL 18 IS 3 BP 29 EP 32 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DD1RT UT WOS:000369699900005 PM 26665209 ER PT J AU Zygoura, V Papavasileiou, E Vavvas, DG Cortis, D Eleftheriadis, H Jackson, TL AF Zygoura, Vasiliki Papavasileiou, Evangelia Vavvas, Demetrios G. Cortis, Dominic Eleftheriadis, Haralabos Jackson, Timothy L. TI Real-world treatment of diabetic macular oedema: a comparison of combined ranibizumab plus macular LASER with macular LASER monotherapy SO HELLENIC JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE Anti-VEGF factors; Diabetic macular oedema; LASER photocoagulation; Optical coherence tomography ID ENDOTHELIAL GROWTH-FACTOR; SERUM-LIPID LEVELS; DEFERRED LASER; INTRAVITREAL RANIBIZUMAB; CONTROLLED-TRIAL; PROMPT LASER; HARD EXUDATE; RISK-FACTORS; RETINOPATHY; TRIAMCINOLONE AB Objective: To study real world outcomes of ranibizumab (Lucentis) intravitreal injection in diabetic macular oedema (DMO). Subjects and Methods: We included 100 patients with DMO. Those who had optical coherence tomography central retinal thickness (CRT) of 400 mu m or more (Group 1) underwent combination treatment with ranibizumab and macular LASER, while those with CRT less than 400 mu m (Group 2) had LASER monotherapy. The primary outcome measure was change in best corrected visual acuity (BCVA) from baseline. Secondary outcomes were change of CRT from baseline, the number of intravitreal injections in group one during the first and second year of follow-up and the proportion of LASER sessions in both groups at 2 years follow-up. Patients' lipid profile was compared to the presence and extent of macular hard exudates, quantified using masked readers and image analysis software. Results: Group 1 showed better outcomes in terms of BCVA and CRT compared to Group 2 during the two-year follow-up period. The mean number of ranibizumab intravitreal injections in Group 1 was reduced from 3.86 (standard deviation +/- 1.37) in the first year to 2.02 in the second year. At 2 years, Group 1 had a higher proportion of individuals that had undergone 3 macular LASER treatments (4% Group 1, 28% Group 2). The presence of hard exudates was associated with higher total cholesterol (P=0.004 and P=0.041 group 1 and 2 respectively) and with higher low density lipoprotein (LDL) cholesterol (P=0.01 and P=0.045 respectively). The size of hard exudates was associated with higher total cholesterol (P=0.02 and P=0.03 respectively) and with higher LDL cholesterol (P=0.003 and P=0.01 respectively). Neither high density lipoprotein (HDL) cholesterol, nor triglycerides were related to the presence or size of hard exudates. No serious adverse events were attributed to either LASER or ranibizumab. Conclusions: Combination treatment of intravitreal ranibizumab injections and macular LASER appears safe and effective over two years. The need for injection declines over time. There is an association between higher levels of serum total and LDL cholesterol and the presence and the extent of hard exudates. C1 [Zygoura, Vasiliki] Moorfields Eye Hosp, City Rd, London EC1V 2PD, England. [Papavasileiou, Evangelia; Vavvas, Demetrios G.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Papavasileiou, Evangelia; Eleftheriadis, Haralabos; Jackson, Timothy L.] Kings Coll Hosp London, London, England. [Cortis, Dominic] Univ Leicester, Dept Math, Leicester LE1 7RH, Leics, England. [Cortis, Dominic] Univ Malta, Dept Insurance, Msida, Malta. [Jackson, Timothy L.] Kings Coll London, London WC2R 2LS, England. RP Zygoura, V (reprint author), Moorfields Eye Hosp, City Rd, London EC1V 2PD, England. EM vasilikizygoura@yahoo.gr NR 49 TC 2 Z9 2 U1 3 U2 3 PU HELLENIC SOC NUCLEAR MEDICINE PI THESSALONIKI PA 51 HERMU ST, THESSALONIKI, 546 23, GREECE SN 1790-5427 J9 HELL J NUCL MED JI Hell. J. Nucl. Med. PD SEP-DEC PY 2015 VL 18 IS 3 BP 33 EP 41 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DD1RT UT WOS:000369699900006 PM 26665210 ER PT J AU Xu, JJ Hong, JX Sun, XH Liu, ZG Mashaghi, A Inomata, T Lu, Y Li, YM Wu, D Yang, YJ Wei, AJ Zhao, YJ Lu, C AF Xu, Jianjiang Hong, Jiaxu Sun, Xinghuai Liu, Zuguo Mashaghi, Alireza Inomata, Takenori Lu, Yi Li, Yimin Wu, Dan Yang, Yujing Wei, Anji Zhao, Yujin Lu, Chun TI Combined Lacrimal Passage Probing and Tobramycin/Dexamethasone Ophthalmic Ointment Infiltration A Minimally Invasive Surgical Procedure for Incomplete Nasolacrimal Duct Obstruction SO MEDICINE LA English DT Article ID SILICONE TUBE INTUBATION; BALLOON DACRYOCYSTOPLASTY; ADULTS; MANAGEMENT; DILATION; EPIPHORA; SYSTEM AB The optimal treatment strategy for an incomplete nasolacrimal duct obstruction (INDO) is still being debated. The aim of this study is to evaluate the treatment results of combined lacrimal passage probing and tobramycin/dexamethasone ophthalmic ointment infiltration (PIO, Probing and Injection) for INDO.In this retrospective, noncomparative case series, 397 consecutive adult patients with INDO treated at Shanghai Eye, Ear, Nose and Throat Hospital were enrolled. Records of the patients were reviewed. With the help of a modified 23-gauge lacrimal cannula, the PIO surgery was performed for the INDO-identified patients. The main outcome measures were resolution of tearing and complications. The relationship between successful outcome and clinical characteristics was analyzed.The surgery was performed successfully in all of the enrolled cases. No intraoperative complications were found in the procedure. The average follow-up time was 7.9 months. Three hundred patients (75.6%) experienced complete resolution of their symptoms after the surgery. Ninety-seven patients (24.4%) showed a partial improvement (1.8%), no improvement (18.4%), or a worsening of symptoms (4.3%). Of the 97 surgical-failure patients, 90 required silicone intubation or external dacryocystorhinostomy, and 94% were finally resolved. The most common postoperative complications were mild nasal bleeding in 41 patients, drug residues in 12 patients (6 developed the complete obstruction), and a slit punctum in 8 patients. Multivariate logistic regression analysis revealed that unilateral eye onset, not having a discharge at baseline, and not having postoperative drug residues were significant factors determining successful outcome.The PIO surgery is an effective, safe, timesaving, easy-to-perform, and minimally invasive technique for treating INDO. C1 [Xu, Jianjiang; Hong, Jiaxu; Sun, Xinghuai; Lu, Yi; Li, Yimin; Wu, Dan; Yang, Yujing; Wei, Anji; Zhao, Yujin; Lu, Chun] Fudan Univ, Shanghai Med Coll, Eye Ear Nose & Throat Hosp, Dept Ophthalmol & Visual Sci, Shanghai 200031, Peoples R China. [Hong, Jiaxu; Liu, Zuguo] Xiamen Univ, Sch Life Sci, Fujian Prov Key Lab Ophthalmol & Visual Sci, Xiamen, Fujian, Peoples R China. [Hong, Jiaxu; Mashaghi, Alireza] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Sun, Xinghuai] Inst Brain Sci, China State Key Lab Med Neurobiol, Shanghai, Peoples R China. [Sun, Xinghuai] Natl Hlth & Family Planning Commiss, Key Lab Myopia, Shanghai, Peoples R China. [Inomata, Takenori] Juntendo Univ, Sch Med, Dept Ophthalmol, Tokyo 113, Japan. RP Hong, JX (reprint author), Fudan Univ, Dept Ophthalmol & Visual Sci, Eye Ear Nose & Throat Hosp, Sch Shanghai Med, 83 Fenyang Rd, Shanghai 200031, Peoples R China. EM jiaxu_hong@163.com FU Key Clinic Medicine Research Program, the Ministry of Health, China [201302015]; Ministry of Science and Technology, China [2012BAI08B01]; National Natural Science Foundation of China [81170817, 81200658, 81300735, 81270978, U1205025, 81330022]; Scientific Research Program, Science and Technology Commission of Shanghai Municipality, Shanghai [13441900900, 13430720400]; Chinese Postdoctoral Fund [XMU135890]; New Technology Joint Research Project in Shanghai Hospitals [SHDC12014114] FX The authors were supported by grants from the Key Clinic Medicine Research Program, the Ministry of Health, China (201302015); the National Science and Technology Research Program, the Ministry of Science and Technology, China (2012BAI08B01); the National Natural Science Foundation of China (81170817, 81200658, 81300735, 81270978, U1205025, and 81330022); the Scientific Research Program, Science and Technology Commission of Shanghai Municipality, Shanghai (13441900900, 13430720400); the Chinese Postdoctoral Fund (XMU135890); and the New Technology Joint Research Project in Shanghai Hospitals (SHDC12014114). The sponsor or funding organization had no role in the design or conduct of this research. NR 19 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 0025-7974 EI 1536-5964 J9 MEDICINE JI Medicine (Baltimore) PD SEP PY 2015 VL 94 IS 36 AR e1483 DI 10.1097/MD.0000000000001483 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA DC9HL UT WOS:000369531900026 PM 26356711 ER PT J AU Patorno, E Glynn, R Schneeweiss, S Liu, J Bateman, B AF Patorno, Elisabetta Glynn, Robert Schneeweiss, Sebastian Liu, Jun Bateman, Brian TI Perioperative Beta-Blocker (BB) Therapy in Non-cardiac Surgery and the Risk of In-hospital Myocardial Infarction (MI), Stroke, and Mortality SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Patorno, Elisabetta; Glynn, Robert; Schneeweiss, Sebastian; Liu, Jun; Bateman, Brian] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Patorno, Elisabetta; Glynn, Robert; Schneeweiss, Sebastian; Liu, Jun; Bateman, Brian] Harvard Univ, Sch Med, Boston, MA USA. [Bateman, Brian] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. RI Schneeweiss, Sebastian/C-2125-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP PY 2015 VL 24 SU 1 SI SI MA 7 BP 4 EP 5 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DD5QW UT WOS:000369980200008 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 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 Aronow, Herbert D. Johnston, Joseph A. Brott, Thomas G. Setoguchi, Soko TI Outcomes of Carotid Artery Stenting (CAS) in Older Patients with Carotid Stenosis SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Jalbert, Jessica J.; Rothman, Andrew T.; Seeger, John D.; Kumamaru, Hiraku; Williams, Lauren A.; Chen, Chih-Ying; Liu, Jun] Harvard Univ, Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Sch Med, Boston, MA 02115 USA. [Jalbert, Jessica J.] LA SER Analyt, New York, NY USA. [Nguyen, Louis L.] Brigham & Womens Hosp, Div Vasc & Endovasc Surg, Boston, MA 02115 USA. [Gerhard-Herman, Marie D.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Div Cardiovasc Med, Boston, MA 02114 USA. [White, Christopher J.] Ochsner Clin Fdn, New Orleans, LA USA. [Aronow, Herbert D.] St Joseph Mercy Hosp, Cardiac Catheterizat Lab, Ypsilanti, MI USA. [Johnston, Joseph A.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Brott, Thomas G.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Setoguchi, Soko] Duke Clin Res Inst, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP PY 2015 VL 24 SU 1 SI SI MA 9 BP 5 EP 6 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DD5QW UT WOS:000369980200010 ER PT J AU Patorno, E Everett, B Goldfine, A Glynn, R Liu, J Kim, S AF Patorno, Elisabetta Everett, Brendan Goldfine, Allison Glynn, Robert Liu, Jun Kim, Seoyoung TI Cardiovascular Safety and Effectiveness of Glucagon-like Peptide-1 Receptor Agonists (GLP-1-RAs) in Routine Care SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Patorno, Elisabetta; Glynn, Robert; Liu, Jun; Kim, Seoyoung] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Patorno, Elisabetta; Glynn, Robert; Liu, Jun; Kim, Seoyoung] Harvard Univ, Sch Med, Boston, MA USA. [Everett, Brendan] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Goldfine, Allison] Joslin Diabet Ctr, Clin Res, Boston, MA 02215 USA. [Kim, Seoyoung] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP PY 2015 VL 24 SU 1 SI SI MA 11 BP 6 EP 7 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DD5QW UT WOS:000369980200012 ER PT J AU Rough, K Huybrechts, KF Hernandez-Diaz, S Desai, RJ Patorno, E Bateman, BT AF Rough, Kathryn Huybrechts, Krista F. Hernandez-Diaz, Sonia Desai, Rishi J. Patorno, Elisabetta Bateman, Brian T. TI Validation of the Overutilization Monitoring System to Detect Opioid Misuse Using Claims Data SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Rough, Kathryn; Hernandez-Diaz, Sonia] Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Rough, Kathryn; Huybrechts, Krista F.; Desai, Rishi J.; Patorno, Elisabetta; Bateman, Brian T.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Rough, Kathryn; Huybrechts, Krista F.; Desai, Rishi J.; Patorno, Elisabetta; Bateman, Brian T.] Harvard Univ, Sch Med, Boston, MA USA. [Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP PY 2015 VL 24 SU 1 SI SI MA 44 BP 26 EP 26 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DD5QW UT WOS:000369980200045 ER PT J AU Lo-Ciganic, WH Gellad, WF Gordon, AJ Cochrane, G Donohue, JM AF Lo-Ciganic, Wei-Hsuan Gellad, Walid F. Gordon, Adam J. Cochrane, Gerald Donohue, Julie M. TI Trajectories of Buprenorphine Treatment and Associated Emergency Department and Inpatient Use in a Large Medicaid Program SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Lo-Ciganic, Wei-Hsuan] Univ Arizona, Coll Pharm, Dept Pharm Practice & Sci, Tucson, AZ 85721 USA. [Gellad, Walid F.; Gordon, Adam J.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Gellad, Walid F.; Gordon, Adam J.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Cochrane, Gerald] Univ Pittsburgh, Sch Social Work, Pittsburgh, PA 15260 USA. [Donohue, Julie M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP PY 2015 VL 24 SU 1 SI SI MA 47 BP 27 EP 28 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DD5QW UT WOS:000369980200048 ER PT J AU Song, ZR Donneyong, MM Choudhry, NK AF Song, Zirui Donneyong, Macarius M. Choudhry, Niteesh K. TI Natural Behavioral Triggers of Adherence: Evidence from Time Shocks SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Song, Zirui] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Donneyong, Macarius M.; Choudhry, Niteesh K.] Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP PY 2015 VL 24 SU 1 SI SI MA 114 BP 66 EP 67 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DD5QW UT WOS:000369980200114 ER PT J AU Linsky, A Simon, SR Stolzmann, K Meterko, M AF Linsky, Amy Simon, Steven R. Stolzmann, Kelly Meterko, Mark TI Clinical provider experiences with medication discontinuation SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Linsky, Amy; Simon, Steven R.; Stolzmann, Kelly; Meterko, Mark] VA Boston Healthcare Syst, Boston, MA USA. [Linsky, Amy] Boston Univ, Sch Med, Boston, MA 02118 USA. [Simon, Steven R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Meterko, Mark] Boston Univ, Sch Publ Hlth, 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 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP PY 2015 VL 24 SU 1 SI SI MA 160 BP 92 EP 92 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DD5QW UT WOS:000369980200159 ER PT J AU Gross, R Bellamy, SL Ratshaa, B Han, XY Steenhoff, AP Mosepele, M Bisson, GP AF Gross, Robert Bellamy, Scarlett L. Ratshaa, Bakgaki Han, Xiaoyan Steenhoff, Andrew P. Mosepele, Mosepele Bisson, Gregory P. TI Effects of sex and alcohol use on antiretroviral therapy outcomes in Botswana SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Gross, Robert; Bisson, Gregory P.] Univ Penn, Perelman Sch Med, Med & Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Bellamy, Scarlett L.; Han, Xiaoyan] Univ Penn, Perelman Sch Med, Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Ratshaa, Bakgaki; Steenhoff, Andrew P.] Botswana UPenn Partnership, Gaborone, Botswana. [Mosepele, Mosepele] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP PY 2015 VL 24 SU 1 SI SI MA 271 BP 151 EP 151 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DD5QW UT WOS:000369980200262 ER PT J AU Park, Y Hernandez-Diaz, S Bateman, BT Patorno, E Desai, RJ Mogun, H Huybrechts, KF AF Park, Yoonyoung Hernandez-Diaz, Sonia Bateman, Brian T. Patorno, Elisabetta Desai, Rishi J. Mogun, Helen Huybrechts, Krista F. TI Utilization of Antipsychotics and Stimulants during Pregnancy among Publicly Insured Women in the United States SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Park, Yoonyoung; Bateman, Brian T.; Patorno, Elisabetta; Desai, Rishi J.; Mogun, Helen; Huybrechts, Krista F.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Park, Yoonyoung; Bateman, Brian T.; Patorno, Elisabetta; Desai, Rishi J.; Mogun, Helen; Huybrechts, Krista F.] Harvard Univ, Sch Med, Boston, MA USA. [Park, Yoonyoung; Hernandez-Diaz, Sonia] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP PY 2015 VL 24 SU 1 SI SI MA 366 BP 205 EP 206 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DD5QW UT WOS:000369980200357 ER PT J AU Bateman, BT Huybrechts, KF Patorno, E Desai, R Hernandez-Diaz, S AF Bateman, Brian T. Huybrechts, Krista F. Patorno, Elisabetta Desai, Rishi Hernandez-Diaz, Sonia TI Attention Deficit Hyperactivity Medications during Pregnancy and the Risk of Congenital Cardiac Malformations: A Cohort Study SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Bateman, Brian T.; Huybrechts, Krista F.; Patorno, Elisabetta; Desai, Rishi] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Bateman, Brian T.; Huybrechts, Krista F.; Patorno, Elisabetta; Desai, Rishi] Harvard Univ, Sch Med, Boston, MA USA. [Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. [Hernandez-Diaz, Sonia] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP PY 2015 VL 24 SU 1 SI SI MA 368 BP 206 EP 207 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DD5QW UT WOS:000369980200359 ER PT J AU Huybrechts, KF Bateman, BT Patorno, E Desai, R Mogun, H Hernandez-Diaz, S AF Huybrechts, Krista F. Bateman, Brian T. Patorno, Elisabetta Desai, Rishi Mogun, Helen Hernandez-Diaz, Sonia TI Antipsychotic Medication Use during Pregnancy and Risk of Congenital Cardiac Malformations SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Huybrechts, Krista F.; Bateman, Brian T.; Patorno, Elisabetta; Desai, Rishi; Mogun, Helen] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Huybrechts, Krista F.; Bateman, Brian T.; Patorno, Elisabetta; Desai, Rishi; Mogun, Helen] Harvard Univ, Sch Med, Boston, MA USA. [Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. [Hernandez-Diaz, Sonia] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP PY 2015 VL 24 SU 1 SI SI MA 367 BP 206 EP 206 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DD5QW UT WOS:000369980200358 ER PT J AU Patorno, E Huybrechts, K Bateman, B Desai, R Mogun, H Hernandez-Diaz, S AF Patorno, Elisabetta Huybrechts, Krista Bateman, Brian Desai, Rishi Mogun, Helen Hernandez-Diaz, Sonia TI The Safety of Mood Stabilizers in Pregnant Women with Regard to the Risk of Congenital Cardiac Malformations SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Patorno, Elisabetta; Huybrechts, Krista; Bateman, Brian; Desai, Rishi; Mogun, Helen] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Patorno, Elisabetta; Huybrechts, Krista; Bateman, Brian; Desai, Rishi; Mogun, Helen] Harvard Univ, Sch Med, Boston, MA USA. [Bateman, Brian] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. [Hernandez-Diaz, Sonia] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP PY 2015 VL 24 SU 1 SI SI MA 369 BP 207 EP 208 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DD5QW UT WOS:000369980200360 ER PT J AU Lo-Ciganic, WH Donohue, JM Thorpe, JM Perera, S Thorpe, CT Marcum, ZA Gellad, WF AF Lo-Ciganic, Wei-Hsuan Donohue, Julie M. Thorpe, Joshua M. Perera, Subashan Thorpe, Carolyn T. Marcum, Zachary A. Gellad, Walid F. TI Using Machine Learning to Examine Medication Adherence Thresholds and Risk of Hospitalization SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Lo-Ciganic, Wei-Hsuan] Univ Arizona, Coll Pharm, Tucson, AZ 85721 USA. [Donohue, Julie M.] Univ Pittsburgh, Dept Hlth Policy & Management, Pittsburgh, PA USA. [Thorpe, Joshua M.; Thorpe, Carolyn T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. [Thorpe, Joshua M.; Thorpe, Carolyn T.; Gellad, Walid F.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res, Pittsburgh, PA USA. [Thorpe, Joshua M.; Thorpe, Carolyn T.; Gellad, Walid F.] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Perera, Subashan] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Perera, Subashan; Gellad, Walid F.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Marcum, Zachary A.] Univ Washington, Sch Pharm, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP PY 2015 VL 24 SU 1 SI SI MA 374 BP 210 EP 211 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DD5QW UT WOS:000369980200365 ER PT J AU Velentgas, P Bosco, JL Franke, K Coleman, AL Lum, FC Gliklich, R Park, J Su, ZH AF Velentgas, Priscilla Bosco, Jaclyn Lf Franke, Kristina Coleman, Anne L. Lum, Flora C. Gliklich, Richard Park, Julie Su, Zhaohui TI Comparing Three-way and Pairwise Propensity Score Matching Approaches for Analyses of a Real-world Comparative Effectiveness Study of Glaucoma Therapies (RiGOR) SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Velentgas, Priscilla; Bosco, Jaclyn Lf; Franke, Kristina; Park, Julie; Su, Zhaohui] Quintiles, Real World & Late Phase Res, Cambridge, MA USA. [Coleman, Anne L.] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. [Coleman, Anne L.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Lum, Flora C.] Fdn Acad Ophthalmol, H Dunbar Hoskins Jr Ctr Qual Eye Care, San Francisco, CA USA. [Gliklich, Richard] Harvard Univ, Massachusetts Eye & Ear Infirm, 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 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP PY 2015 VL 24 SU 1 SI SI MA 386 BP 217 EP 218 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DD5QW UT WOS:000369980200377 ER PT J AU Oberg, AS D'Onofrio, BM Rickert, ME Hernandez-Diaz, S Bateman, BT AF Oberg, Anna S. D'Onofrio, Brian M. Rickert, Martin E. Hernandez-Diaz, Sonia Bateman, Brian T. TI Labor Induction and Offspring Risk of Autism Spectrum Disorder SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Oberg, Anna S.; Hernandez-Diaz, Sonia] Harvard Univ, T Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Oberg, Anna S.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [D'Onofrio, Brian M.; Rickert, Martin E.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN USA. [Bateman, Brian T.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Bateman, Brian T.] Harvard Univ, Sch Med, Boston, MA USA. [Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP PY 2015 VL 24 SU 1 SI SI MA 419 BP 237 EP 237 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DD5QW UT WOS:000369980200410 ER PT J AU Andrade, S Perez-Gutthann, S Hua, W Kawai, A Martin, D Reichman, M Toh, D AF Andrade, Susan Perez-Gutthann, Susana Hua, Wei Kawai, Alison Martin, David Reichman, Marsha Toh, Darren TI Building a Sustainable Surveillance System to Monitor the Use and Safety of Medical Products in Pregnancy SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Andrade, Susan] Meyers Primary Care Inst, Worcester, MA USA. [Perez-Gutthann, Susana] RTI Hlth Solut, Barcelona, Spain. [Hua, Wei; Reichman, Marsha] US FDA, Silver Spring, MD USA. [Kawai, Alison; Toh, Darren] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Kawai, Alison; Toh, Darren] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Martin, David] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP PY 2015 VL 24 SU 1 SI SI MA 423 BP 239 EP 240 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DD5QW UT WOS:000369980200414 ER PT J AU Kohler, O Gasse, C Mors, O Nierenberg, A Petersen, L Ostergaard, SD AF Kohler, Ole Gasse, Christiane Mors, Ole Nierenberg, Andrew Petersen, Liselotte Ostergaard, Soren Dinesen TI Comparative Effectiveness and Safety of SSRI Treatment with or without Concomitant Use of Statins: A Population-based Study SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Kohler, Ole; Mors, Ole; Ostergaard, Soren Dinesen] Aarhus Univ Hosp, Res Unit P, Risskov, Denmark. [Gasse, Christiane; Petersen, Liselotte] Aarhus Univ, Natl Ctr Register Based Res, Aarhus, Denmark. [Nierenberg, Andrew] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, 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 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP PY 2015 VL 24 SU 1 SI SI MA 599 BP 342 EP 343 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DD5QW UT WOS:000369980200590 ER PT J AU Jalbert, JJ Nguyen, LL Gerhard-Herman, MD Kumamaru, H Williams, LA Chen, CY Liu, J Rothman, AT Jaff, MR Seeger, JD Aronow, HD Johnston, JA Brott, TG White, CJ Setoguchi, S AF Jalbert, Jessica J. Nguyen, Louis L. Gerhard-Herman, Marie D. Kumamaru, Hiraku Williams, Lauren A. Chen, Chih-Ying Liu, Jun Rothman, Andrew T. Jaff, Michael R. Seeger, John D. Aronow, Herbert D. Johnston, Joseph A. Brott, Thomas G. White, Christopher J. Setoguchi, Soko TI Comparative Effectiveness of Carotid Artery Stenting (CAS) and Carotid Endarterectomy (CEA) among Medicare Beneficiaries Treated in Routine Clinical Practice SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Jalbert, Jessica J.; Kumamaru, Hiraku; Williams, Lauren A.; Chen, Chih-Ying; Liu, Jun; Rothman, Andrew T.; Seeger, John D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Jalbert, Jessica J.] LA SER Analyt, New York, NY USA. [Nguyen, Louis L.] Brigham & Womens Hosp, Div Vasc & Endovasc Surg, Boston, MA 02115 USA. [Gerhard-Herman, Marie D.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Div Cardiovasc Med, Boston, MA 02114 USA. [Aronow, Herbert D.] St Joseph Mercy Hosp, Cardiac Catheterizat Lab, Ypsilanti, MI USA. [Johnston, Joseph A.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Brott, Thomas G.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [White, Christopher J.] Ochsner Clin Fdn, New Orleans, LA USA. [Setoguchi, Soko] Duke Clin Res Inst, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP PY 2015 VL 24 SU 1 SI SI MA 612 BP 350 EP 350 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DD5QW UT WOS:000369980200603 ER PT J AU Lai, ECC Wong, MB Iwata, I Zhang, YH Hsieh, CY Yang, YHK Setoguchi, S AF Lai, Edward Chia-Cheng Wong, Monera B. Iwata, Isao Zhang, Yinghong Hsieh, Cheng-Yang Yang, Yea-Huei Kao Setoguchi, Soko TI Use of Different Formulations Rivastigmine and Risk of Cardiovascular Adverse Events SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Lai, Edward Chia-Cheng; Zhang, Yinghong; Setoguchi, Soko] Duke Clin Res Inst, Durham, NC USA. [Lai, Edward Chia-Cheng; Hsieh, Cheng-Yang; Yang, Yea-Huei Kao] Inst Clin Pharm & Pharmaceut Sci, Tainan, Taiwan. [Wong, Monera B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Iwata, Isao] Univ N Carolina, Div Geriatr Med, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP PY 2015 VL 24 SU 1 SI SI MA 619 BP 354 EP 354 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DD5QW UT WOS:000369980200610 ER PT J AU Bateman, BT Hernandez-Diaz, S Patorno, E Desai, R Huybrechts, KF AF Bateman, Brian T. Hernandez-Diaz, Sonia Patorno, Elisabetta Desai, Rishi Huybrechts, Krista F. TI ACE Inhibitors During the First Trimester of Pregnancy and the Risk of Congenital Malformations: A Cohort Study SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Bateman, Brian T.; Patorno, Elisabetta; Desai, Rishi; Huybrechts, Krista F.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Bateman, Brian T.; Patorno, Elisabetta; Desai, Rishi; Huybrechts, Krista F.] Harvard Univ, Sch Med, Boston, MA USA. [Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. [Hernandez-Diaz, Sonia] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP PY 2015 VL 24 SU 1 SI SI MA 703 BP 400 EP 401 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DD5QW UT WOS:000369980200692 ER PT J AU Bateman, BT Huybrechts, KF Desai, R Patorno, E Hernandez-Diaz, S AF Bateman, Brian T. Huybrechts, Krista F. Desai, Rishi Patorno, Elisabetta Hernandez-Diaz, Sonia TI Late Pregnancy Exposure to Beta Blockers and the Risks of Neonatal Hypoglycemia and Bradycardia SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Bateman, Brian T.; Huybrechts, Krista F.; Desai, Rishi; Patorno, Elisabetta] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Bateman, Brian T.; Huybrechts, Krista F.; Desai, Rishi; Patorno, Elisabetta] Harvard Univ, Sch Med, Boston, MA USA. [Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. [Hernandez-Diaz, Sonia] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP PY 2015 VL 24 SU 1 SI SI MA 704 BP 401 EP 401 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DD5QW UT WOS:000369980200693 ER PT J AU Mehta, HB Mehta, V Tsai, CL Chen, H Aparasu, R Johnson, ML AF Mehta, Hemalkumar B. Mehta, Vinay Tsai, Chu-Lin Chen, Hua Aparasu, Rajender Johnson, Michael L. TI Comparative Effectiveness of Angiotensin Converting Enzyme (ACE) Inhibitors and Angiotensin Receptor Blockers (ARB) for the Risk of Dementia in Patients With Type 2 Diabetes Mellitus and Hypertension SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Mehta, Hemalkumar B.] Univ Texas Med Branch, Dept Surg, Galveston, TX 77555 USA. [Mehta, Vinay] Merck, Epidemiol, N Wales, PA USA. [Tsai, Chu-Lin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Chen, Hua; Aparasu, Rajender; Johnson, Michael L.] Univ Houston, Dept Pharmaceut Hlth Outcomes & Policy, Houston, TX USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP PY 2015 VL 24 SU 1 SI SI MA 747 BP 427 EP 427 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DD5QW UT WOS:000369980201039 ER PT J AU Jackson, JW Fulchino, L Rogers, J Polinski, J Henderson, DC Schneeweiss, S Fischer, MA AF Jackson, John W. Fulchino, Lisa Rogers, James Polinski, Jennifer Henderson, David C. Schneeweiss, Sebastian Fischer, Michael A. TI Patient and Policy-Level Determinants of Long-Acting Injectable Antipsychotic Use after Relapse: A Nationwide Study of Schizophrenia Patients in the United States SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Jackson, John W.; Fulchino, Lisa; Rogers, James; Polinski, Jennifer; Schneeweiss, Sebastian; Fischer, Michael A.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Jackson, John W.; Schneeweiss, Sebastian] Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Jackson, John W.; Henderson, David C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RI Schneeweiss, Sebastian/C-2125-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP PY 2015 VL 24 SU 1 SI SI MA 877 BP 501 EP 501 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DD5QW UT WOS:000369980201168 ER PT J AU Mehta, HB Mehta, V Tsai, CL Chen, H Aparasu, RR Johnson, ML AF Mehta, Hemalkumar B. Mehta, Vinay Tsai, Chu-Lin Chen, Hua Aparasu, Rajender R. Johnson, Michael L. TI Development and Validation of the RxDx-Dementia Risk Index TO Predict Dementia in Patients with Type 2 Diabetes and Hypertension SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Mehta, Hemalkumar B.] Univ Texas Med Branch, Dept Surg, Galveston, TX 77555 USA. [Mehta, Vinay] Merck, Epidemiol, N Wales, PA USA. [Tsai, Chu-Lin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Chen, Hua; Aparasu, Rajender R.; Johnson, Michael L.] Univ Houston, Dept Pharmaceut Hlth Outcomes & Policy, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP PY 2015 VL 24 SU 1 SI SI MA 980 BP 558 EP 559 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DD5QW UT WOS:000369980201269 ER PT J AU Ho, AYL Vassy, JL Gagnon, DR Gaziano, JM Honerlaw, J Raju, S Wilson, PWF Cho, K AF Ho, Anne Yuk-Lam Vassy, Jason L. Gagnon, David R. Gaziano, J. Michael Honerlaw, Jacqueline Raju, Sanjay Wilson, Peter W. F. Cho, Kelly TI Differential Racial and Regional Effects of Baseline Timeframe on Potential Bias in Risk Factor Assessment Using EHR Data SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Ho, Anne Yuk-Lam; Vassy, Jason L.; Gagnon, David R.; Gaziano, J. Michael; Honerlaw, Jacqueline; Raju, Sanjay; Wilson, Peter W. F.; Cho, Kelly] Boston VA Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Vassy, Jason L.; Gaziano, J. Michael; Cho, Kelly] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA USA. [Gagnon, David R.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Wilson, Peter W. F.] Emory Univ, Cln Cardiovasc Res Inst, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP PY 2015 VL 24 SU 1 SI SI MA 1013 BP 577 EP 577 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DD5QW UT WOS:000369980201301 ER PT J AU Kamdar, MM Edwards, DA Thabet, AM Volney, SJ Rathmell, JP AF Kamdar, Mihir M. Edwards, David A. Thabet, Ashraf M. Volney, Shane J. Rathmell, James P. TI A Novel Modified Retrocrural Approach for Celiac Plexus Block The Single-Needle Retroaortic Technique SO REGIONAL ANESTHESIA AND PAIN MEDICINE LA English DT Article ID PANCREATIC-CANCER; PAIN; NEUROLYSIS; EFFICACY AB For patients with pain from upper abdominal malignancies, celiac plexus neurolysis can provide an effective means of pain control. However, there are instances when traditionally described percutaneous approaches may not be technically feasible. We describe here the successful use of a novel single-needle retroaortic approach as an alternative approach to celiac plexus neurolysis. We present 4 cases of patients with pain from upper abdominal malignancies in whom we performed celiac plexus neurolysis using a novel single-needle retroaortic approach. All 4 patients had significant pain relief and no significant adverse effects from the retroaortic approach. C1 [Kamdar, Mihir M.; Edwards, David A.; Volney, Shane J.; Rathmell, James P.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Thabet, Ashraf M.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. RP Kamdar, MM (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 15 Parkman St,WACC 340, Boston, MA 02114 USA. EM MMKAMDAR@mgh.harvard.edu OI Edwards, David/0000-0003-0123-4805 NR 14 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 1098-7339 EI 1532-8651 J9 REGION ANESTH PAIN M JI Region. Anesth. Pain Med. PD SEP-OCT PY 2015 VL 40 IS 5 BP 610 EP 615 DI 10.1097/AAP.0000000000000290 PG 6 WC Anesthesiology SC Anesthesiology GA DD0OB UT WOS:000369618200023 PM 26222348 ER PT J AU Noiret, L Slater, A Rudolf, J Higgins, J AF Noiret, L. Slater, A. Rudolf, J. Higgins, J. TI Short-Lived and Long-Lived Alloimmunization after Red Blood Cell Transfusion SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting CY OCT 24-27, 2015 CL Anaheim, CA SP AABB C1 [Noiret, L.; Higgins, J.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Slater, A.] Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. [Rudolf, J.] Massachusetts Gen Hosp, Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD SEP PY 2015 VL 55 SU 3 SI SI MA S4-010A BP 7A EP 7A PG 1 WC Hematology SC Hematology GA DD5GS UT WOS:000369951500011 ER PT J AU Dzik, W Ziman, A Cohn, CS Pai, M Lozano, M Kaufman, RM Delaney, M Selleng, K Murphy, M Hervig, T Yazer, MH AF Dzik, W. Ziman, A. Cohn, C. S. Pai, M. Lozano, M. Kaufman, R. M. Delaney, M. Selleng, K. Murphy, M. Hervig, T. Yazer, M. H. TI Survival Following Ultra-massive Transfusion (UMT): A Review Of 1360 Cases SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting CY OCT 24-27, 2015 CL Anaheim, CA SP AABB C1 [Dzik, W.] Massachusetts Gen Hosp, Transfus Med, Boston, MA 02114 USA. [Ziman, A.] Univ Calif Los Angeles, Transfus Med, Los Angeles, CA USA. [Cohn, C. S.] Univ Minnesota, Transfus Med, Minneapolis, MN USA. [Pai, M.] McMaster Univ, Transfus Med, Hamilton, ON, Canada. [Lozano, M.] Univ Clin Hosp, Hemotherapy Hemostasis, Barcelona, Spain. [Kaufman, R. M.] Brigham & Womens Hosp, Transfus Med, Boston, MA 02115 USA. [Delaney, M.] Univ Washington, Transfus Med, Seattle, WA 98195 USA. [Selleng, K.] Ernst Moritz Arndt Univ Greifswald, Transfus Med, Greifswald, Germany. [Murphy, M.] John Radcliffe, Transfus Med, Headington, England. [Hervig, T.] Haukeland Hosp, Transfus Med, N-5021 Bergen, Norway. [Yazer, M. H.] Inst Transfus Med, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD SEP PY 2015 VL 55 SU 3 SI SI MA SP286 BP 171A EP 172A PG 2 WC Hematology SC Hematology GA DD5GS UT WOS:000369951500376 ER PT J AU Weinstein, DF AF Weinstein, Debra F. TI The Elusive Goal of Accountability in Graduate Medical Education SO ACADEMIC MEDICINE LA English DT Editorial Material ID DUTY HOUR REFORM AB Repeated calls for greater accountability of graduate medical education (GME) have been issued in recent years. In this context, Kenneth Ludmerer's Let Me Heal examines the issue of duty hours limits and paints a picture of failed accountability. The ways in which duty hours regulations have failed are discussed, pointing toward a need to focus on goals and outcomes (such as patient safety) rather than process (such as schedules and shift length). This Commentary considers key issues-who should be accountable, for what, and to whom?-and proposes a potential path for achieving accountability in GME. The author draws from consensus reports published by the Josiah Macy Jr. Foundation and the Institute of Medicine to outline the case for why the U.S. system of GME should be accountable to the public, to individual patients, and to the residents and fellows being educated. Domains of accountability include graduating competent physicians, producing the right workforce, and ensuring an efficient and cost-effective training process that is designed to protect patients. In addition, the author argues that GME should be accountable for providing trainees with reasonable working conditions and compensation. Key requirements for achieving meaningful GME accountability are proposed, including (1) a more effective partnership with the public; (2) explicit goals and assigned responsibilities, reflecting reasonable expectations of what GME can accomplish; (3) reliable metrics for GME outcomes; and (4) a governance system that provides coordination and has the authority to effect changes. C1 [Weinstein, Debra F.] Partners HealthCare Syst, Med Educ, Boston, MA USA. [Weinstein, Debra F.] Massachusetts Gen Hosp, Dept Med, Med, Boston, MA 02114 USA. [Weinstein, Debra F.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Weinstein, DF (reprint author), Massachusetts Gen Hosp, Bulfinch 230,55 Fruit St, Boston, MA 02114 USA. EM dweinstein@partners.org NR 8 TC 3 Z9 3 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD SEP PY 2015 VL 90 IS 9 BP 1188 EP 1190 DI 10.1097/ACM.0000000000000834 PG 3 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA DD0FD UT WOS:000369594900011 PM 26177525 ER PT J AU Liao, JM Co, JP Kachalia, A AF Liao, Joshua M. Co, John P. Kachalia, Allen TI Providing Educational Content and Context for Training the Next Generation of Physicians in Quality Improvement SO ACADEMIC MEDICINE LA English DT Article ID PATIENT SAFETY; RESIDENTS; CURRICULUM; ENGAGEMENT; PROGRAM; FELLOWS; SYSTEM; CARE AB Amid calls for graduate medical education (GME) to better prepare a workforce that can address growing challenges in health care quality and cost, institutions must find ways to more effectively educate and engage housestaff in quality improvement (QI) initiatives. Although the benefits for trainees and institutions alike can be significant, creating and maintaining successful strategies has proven challenging. Multiple barriers (e.g., variable backgrounds and needs of trainees) have clouded the educational and clinical effectiveness of many efforts. Recent findings suggest that trainee engagement in QI is lacking and that contextual support for practice-based learning and systems-based practice is often suboptimal. Meaningful GME reform must include changes in how institutions approach QI education, particularly in how they create appropriate learning environments for trainees. Institutions can achieve these goals and foster a positive QI culture by aligning housestaff QI teaching with institutional priorities in several ways. First, they can create common, institutional-level QI curricula to standardize expectations for learners across training levels and specialties. Second, they can engage housestaff in ongoing institutional QI efforts by encouraging these trainees to develop and execute QI projects or assemble QI-focused groups that include faculty and institutional leaders. Third, institutions can appoint housestaff to institutional QI committees and have housestaff groups review and endorse proposed QI initiatives to enhance operational decision making. Institutions can leverage the new Accreditation Council for Graduate Medical Education Clinical Learning Environment Review program to implement these strategies, measure progress, and realize important gains in housestaff QI education. C1 [Liao, Joshua M.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Liao, Joshua M.; Kachalia, Allen] Harvard Univ, Sch Med, Med, 75 Francis St, Boston, MA 02115 USA. [Liao, Joshua M.] Brigham & Womens Hosp, Housestaff Safety & Qual Council, 75 Francis St, Boston, MA 02115 USA. [Co, John P.] Partners HealthCare, Grad Med Educ, Boston, MA USA. [Co, John P.; Kachalia, Allen] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Co, John P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Co, John P.] Massachusetts Gen Hosp Children, Outpatient Qual & Safety, Boston, MA USA. [Co, John P.] Harvard Univ, Sch Med, Pediat, Boston, MA USA. RP Liao, JM (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.; Liao, JM (reprint author), Harvard Univ, Sch Med, Med, 75 Francis St, Boston, MA 02115 USA. EM jmliao@partners.org NR 29 TC 4 Z9 4 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD SEP PY 2015 VL 90 IS 9 BP 1241 EP 1245 DI 10.1097/ACM.0000000000000799 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA DD0FD UT WOS:000369594900023 PM 26312604 ER PT J AU Shtasel, D Hobbs-Knutson, K Tolpin, H Weinstein, D Gottlieb, GL AF Shtasel, Derri Hobbs-Knutson, Katherine Tolpin, Harriet Weinstein, Debra Gottlieb, Gary L. TI Developing a Pipeline for the Community-Based Primary Care Workforce and Its Leadership: The Kraft Center for Community Health Leadership's Fellowship and Practitioner Programs SO ACADEMIC MEDICINE LA English DT Editorial Material ID PHYSICIANS AB Problem Community health centers (CHCs) face challenges recruiting and retaining primary care clinicians. Providing advanced training that enhances clinical skills within a public health framework, teaches leadership, protects time for scholarly activities, and focuses on the social mission may be a successful career development strategy. Approach In July 2012, the Kraft Center for Community Health Leadership developed and implemented two 2-year programs to develop physician and nursing leaders with blended academic-community career paths and identities. The fellowship program for physicians and the practitioner program for early-career physicians and advanced practice nurses include mentored practice in a CHC; monthly learning days; completion of a community-based research project; and, for fellows, matriculation in an MPH program and engagement in a bimonthly leadership seminar. Outcomes The first classes of 5 fellows and 14 practitioners graduated in June 2014. All 5 fellowship graduates were offered full-time positions at the CHCs where they practiced, and 2 have accepted leadership positions at their CHCs. All 14 practitioner graduates remain in community health, 5 have accepted leadership positions, and 2 have obtained grants to support ongoing projects. Next Steps The authors are tracking graduates' career paths and the programs' impact on CHCs while modifying the programs on the basis of feedback; identifying elements of the programs that may be amenable to more cost-effective delivery; and exploring the potential for federal funding to support expansion of the practitioner program, and for the practitioner program to increase the return on investment provided by the National Health Service Corps. C1 [Shtasel, Derri] Partners HealthCare, Kraft Ctr Community Hlth Leadership, Boston, MA USA. [Shtasel, Derri] Massachusetts Gen Hosp, Div Publ & Community Psychiat, Boston, MA 02114 USA. [Shtasel, Derri; Gottlieb, Gary L.] Harvard Univ, Sch Med, Psychiat, Boston, MA USA. [Hobbs-Knutson, Katherine] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Hobbs-Knutson, Katherine] George Washington Univ, Sch Med & Hlth, Psychiat & Behav Sci & Pediat, Washington, DC USA. [Tolpin, Harriet] Partners HealthCare, Kraft Ctr Community Hlth Leadership, Curriculum, Boston, MA USA. [Weinstein, Debra] Partners HealthCare, Grad Med Educ, Boston, MA USA. [Weinstein, Debra] Harvard Univ, Sch Med, Med, Boston, MA USA. [Gottlieb, Gary L.] Partners Hlth, Boston, MA USA. [Gottlieb, Gary L.] Partners HealthCare, Boston, MA USA. RP Shtasel, D (reprint author), 25 New Chardon St, Boston, MA 02114 USA. EM dshtasel@partners.org NR 6 TC 1 Z9 1 U1 4 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD SEP PY 2015 VL 90 IS 9 BP 1272 EP 1277 DI 10.1097/ACM.0000000000000806 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA DD0FD UT WOS:000369594900030 PM 26312606 ER PT J AU Golshan, M Cirrincione, CT Sikov, WM Berry, DA Jasinski, S Weisberg, TF Somlo, G Hudis, C Winer, E Ollila, DW AF Golshan, Mehra Cirrincione, Constance T. Sikov, William M. Berry, Donald A. Jasinski, Sara Weisberg, Tracey F. Somlo, George Hudis, Clifford Winer, Eric Ollila, David W. CA Alliance Clinical Trials Oncology TI Impact of Neoadjuvant Chemotherapy in Stage II-III Triple Negative Breast Cancer on Eligibility for Breast-conserving Surgery and Breast Conservation Rates Surgical Results From CALGB 40603 (Alliance) SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 135th Annual Meeting of the American-Surgical-Association (ASA) CY APR 23-25, 2015 CL San Diego, CA SP Amer Surg Assoc DE breast-conserving therapy; mastectomy; neoadjuvant therapy; surgery; triple negative breast cancer ID SURGICAL-MANAGEMENT; RANDOMIZED-TRIAL; MASTECTOMY; THERAPY; METAANALYSIS; CARBOPLATIN; REDUCTION; MUTATION AB Objective: To assess the efficacy of neoadjuvant systemic therapy (NST) at increasing the rate of successful breast-conserving therapy (BCT) in triple negative breast cancer. Background: Inducing tumor regression to permit BCT is often cited to support administration of NST. To quantify this benefit, we conducted a surgical companion study to CALGB40603, a randomized phase II, 2x2 factorial trial of neoadjuvant paclitaxel +/- carboplatin +/- bevacizumab (B) followed by doxorubicin plus cyclophosphamide +/- B in stage II-III triple negative breast cancer. Methods: Before and after NST, treating surgeons evaluated BCT candidacy by clinico-radiographic criteria; surgery performed was at surgeon and patient discretion. We measured (1) conversion rates from BCT-ineligible to BCTeligible, (2) surgical choices in BCT candidates, and (3) rates of successful BCT with tumor-free margins. Results: Four hundred four patients were assessable for surgical outcomes. Two hundred nineteen (54%) were BCT candidates before NST. One hundred ninety-seven (90%) remained BCT candidates after NST, of whom 138 (70%) chose BCT, which was successful in 130 (94%). Of 185 (46%) who were not BCT candidates before NST, 78 (42%) converted to candidates with NST. Of these, 53 (68%) chose BCT with a 91% (48/53) success rate. The overall BCT-eligibility rate rose from 54% to 68% (275/404) with NST. Addition of carboplatin, B, or both increased conversion rates. Conclusions: This is the first study to document prospectively a 42% conversion rate from BCT-ineligible to BCT-eligible, resulting in a 14% absolute increase in BCT eligibility. BCT was successful in 93% of patients who opted for it, but 31% of BCT-eligible patients still chose mastectomy. C1 [Golshan, Mehra] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Cirrincione, Constance T.; Jasinski, Sara] Duke Univ, Med Ctr, Alliance Stat & Data Ctr, Durham, NC USA. [Sikov, William M.] Brown Univ, Dept Med Oncol, Women & Infants Hosp, Providence, RI 02912 USA. [Sikov, William M.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Berry, Donald A.] Univ Texas MD Anderson Canc Ctr, Alliance Stat & Data Ctr, Houston, TX 77030 USA. [Weisberg, Tracey F.] Maine Ctr Canc Med, Dept Med Oncol, Scarborough, ME USA. [Somlo, George] City Hope Natl Med Ctr, Med Ctr, Dept Med Oncol, Los Angeles, CA USA. [Hudis, Clifford] Mem Sloan Kettering Canc Ctr, Dept Med Oncol, New York, NY 10021 USA. [Winer, Eric] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ollila, David W.] Univ N Carolina, Dept Surg, Chapel Hill, NC USA. RP Golshan, M (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM mgolshan@partners.org FU NCI NIH HHS [U10 CA180888, CA180888, P30 CA008748, P30 CA016672, U10 CA180791, U10 CA180821, U10 CA180867, U10 CA180882, U10CA180791, U10CA180821, U10CA180867, U10CA180882] NR 18 TC 17 Z9 19 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD SEP PY 2015 VL 262 IS 3 BP 434 EP 439 DI 10.1097/SLA.0000000000001417 PG 6 WC Surgery SC Surgery GA DD0LZ UT WOS:000369612800004 PM 26222764 ER PT J AU Shahian, DM Grover, FL Prager, RL Edwards, FH Filardo, G O'Brien, SM He, X Furnary, AP Rankin, JS Badhwar, V Cleveland, JC Fazzalari, FL Magee, MJ Han, J Jacobs, JP AF Shahian, David M. Grover, Frederick L. Prager, Richard L. Edwards, Fred H. Filardo, Giovanni O'Brien, Sean M. He, Xia Furnary, Anthony P. Rankin, J. Scott Badhwar, Vinay Cleveland, Joseph C., Jr. Fazzalari, Frank L. Magee, Mitchell J. Han, Jane Jacobs, Jeffrey P. TI The Society of Thoracic Surgeons Voluntary Public Reporting Initiative The First 4 Years SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 135th Annual Meeting of the American-Surgical-Association (ASA) CY APR 23-25, 2015 CL San Diego, CA SP Amer Surg Assoc DE outcomes; public reporting; quality measurement; ratings; report card ID PERCUTANEOUS CORONARY INTERVENTION; NEW-YORK-STATE; ACUTE MYOCARDIAL-INFARCTION; ADULT CARDIAC-SURGERY; BYPASS-GRAFTING SURGERY; MEASUREMENT TASK-FORCE; QUALITY MEASUREMENT; HEALTH-CARE; SURGICAL MORTALITY; CLINICAL-OUTCOMES AB Objectives: To evaluate participant characteristics and outcomes during the first 4 years of the Society of Thoracic Surgeons (STS) public reporting program. Background: This is the first detailed analysis of a national, voluntary, cardiac surgery public reporting program using STS clinical registry data andNational Quality Forum-endorsed performance measures. Methods: The distributions of risk-adjusted mortality rates, multidimensional composite performance scores, star ratings, and volumes for public reporting versus nonreporting sites were studied during 9 consecutive semiannual reporting periods (2010-2014). Results: Among 8929 unique observations (similar to 1000 STS participant centers, 9 reporting periods), 916 sites (10.3%) were classified low performing, 6801 (76.2%) were average, and 1212 (13.6%) were high performing. STS public reporting participation varied from 22.2% to 46.3% over the 9 reporting periods. Risk-adjusted, patient-level mortality rates for isolated coronary artery bypass grafting were consistently lower in public reporting versus nonreporting sites (P value range: <0.001-0.0077). Reporting centers had higher composite performance scores and star ratings (23.2% high performing and 4.5% low performing vs 7.6% high performing and 13.8% low performing for nonreporting sites). STS public reporting sites had higher mean annualized coronary artery bypass grafting volumes than nonreporting sites (169 vs 145, P < 0.0001); high-performing programs had higher mean coronary artery bypass grafting volumes (n = 241) than average (n = 139) or low-performing (n = 153) sites. Risk factor prevalence (except reoperation) and expected mortality rates were generally stable during the study period. Conclusions: STS programs that voluntarily participate in public reporting have significantly higher volumes and performance. No evidence of risk aversion was found. C1 [Shahian, David M.] Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,Bulfinch 284, Boston, MA 02114 USA. [Shahian, David M.] Massachusetts Gen Hosp, Ctr Qual & Safety, 55 Fruit St,Bulfinch 284, Boston, MA 02114 USA. [Grover, Frederick L.; Cleveland, Joseph C., Jr.] Univ Colorado, Div Cardiothorac Surg, Aurora, CO USA. [Prager, Richard L.; Fazzalari, Frank L.] Univ Michigan Hlth Syst, Dept Cardiac Surg, Ann Arbor, MI USA. [Edwards, Fred H.] Univ Florida, Div Cardiothorac Surg, Gainesville, FL USA. [Filardo, Giovanni] Baylor Hlth Care Syst, Inst Hlth Care Res & Improvement, Dallas, TX USA. [O'Brien, Sean M.; He, Xia] Duke Clin Res Inst, Durham, NC USA. [Furnary, Anthony P.] Starr Wood Cardiac Grp, Portland, OR USA. [Rankin, J. Scott] Vanderbilt Univ, Nashville, TN 37235 USA. [Badhwar, Vinay] Univ Pittsburgh, Med Ctr, Dept Cardiothorac Surg, Pittsburgh, PA USA. [Magee, Mitchell J.] HCA North Texas Div, Dallas, TX USA. [Han, Jane] Soc Thorac Surg, Chicago, IL USA. [Jacobs, Jeffrey P.] Univ S Florida, All Childrens Hosp, Johns Hopkins All Childrens Heart Inst, St Petersburg, FL 33701 USA. RP Shahian, DM (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,Bulfinch 284, Boston, MA 02114 USA. EM dshahian@partners.org NR 42 TC 10 Z9 10 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD SEP PY 2015 VL 262 IS 3 BP 526 EP 535 DI 10.1097/SLA.0000000000001422 PG 10 WC Surgery SC Surgery GA DD0LZ UT WOS:000369612800015 PM 26258322 ER PT J AU Quraishi, SA De Pascale, G Needleman, JS Nakazawa, H Kaneki, M Bajwa, EK Camargo, CA Bhan, I AF Quraishi, Sadeq A. De Pascale, Gennaro Needleman, Joseph S. Nakazawa, Harumasa Kaneki, Masao Bajwa, Ednan K. Camargo, Carlos A., Jr. Bhan, Ishir TI Effect of Cholecalciferol Supplementation on Vitamin D Status and Cathelicidin Levels in Sepsis: A Randomized, Placebo-Controlled Trial SO CRITICAL CARE MEDICINE LA English DT Article DE 25-hydroxyvitamin; cathelicidin; cholecalciferol; intensive care unit; LL-37; vitamin D ID CRITICALLY-ILL PATIENTS; INTENSIVE-CARE-UNIT; HUMAN ANTIBACTERIAL CATHELICIDIN; SEPTIC SHOCK; D DEFICIENCY; ANTIMICROBIAL PEPTIDES; INTERFERON-GAMMA; CYTOKINE PRODUCTION; MINERAL METABOLISM; ORGAN DYSFUNCTION AB Objectives: To compare changes in vitamin D status and cathelicidin (LL-37) levels in septic ICU patients treated with placebo versus cholecalciferol. Design: Randomized, placebo-controlled, trial. Setting: Medical and surgical ICUs of a single teaching hospital in Boston, MA. Patients: Thirty adult ICU patients. Interventions: Placebo (n = 10) versus 200,000 IU cholecalciferol (n = 10) versus 400,000 IU cholecalciferol (n = 10), within 24 hours of new-onset severe sepsis or septic shock. Measurements and Main Results: Blood samples were obtained at baseline (day 1) and on days 3, 5, and 7, to assess total 25-hydroxyvitamin D, as well as vitamin D-binding protein and albumin to calculate bioavailable 25-hydroxyvitamin D. Plasma LL-37 and high-sensitivity C-reactive protein levels were also measured. At baseline, median (interquartile range) plasma 25-hydroxyvitamin D was 17 ng/mL (13-22 ng/mL) and peaked by day 5 in both intervention groups. Groups were compared using Kruskal-Wallis tests. Relative to baseline, on day 5, median change in biomarkers for placebo, 200,000 IU cholecalciferol, and 400,000 IU cholecalciferol groups, respectively, were as follows: 1) total 25-hydroxyvitamin D, 3% (-3% to 8%), 49% (30-82%), and 69% (55-106%) (p < 0.001); 2) bioavailable 25-hydroxyvitamin D, 4% (-8% to 7%), 45% (40-70%), and 96% (58-136%) (p < 0.01); and 3) LL-37: -17% (-9% to -23%), 4% (-10% to 14%), and 30% (23-48%) (p = 0.04). Change in high-sensitivity C-reactive protein levels did not differ between groups. A positive correlation was observed between bioavailable 25-hydroxyvitamin D and LL-37 (Spearman. = 0.44; p = 0.03) but not for total 25-hydroxyvitamin D and LL-37. Conclusions: High-dose cholecalciferol supplementation rapidly and safely improves 25-hydroxyvitamin D and bioavailable 25-hydroxyvitamin D levels in patients with severe sepsis or septic shock. Changes in bioavailable 25-hydroxyvitamin D are associated with concomitant increases in circulating LL-37 levels. Larger trials are needed to verify these findings and to assess whether optimizing vitamin D status improves sepsis-related clinical outcomes. C1 [Quraishi, Sadeq A.; De Pascale, Gennaro; Kaneki, Masao; Bajwa, Ednan K.; Camargo, Carlos A., Jr.; Bhan, Ishir] Harvard Univ, Sch Med, Boston, MA USA. [Quraishi, Sadeq A.; De Pascale, Gennaro; Needleman, Joseph S.; Nakazawa, Harumasa; Kaneki, Masao] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Kaneki, Masao] Shriners Hosp Children, Boston, MA USA. [Bajwa, Ednan K.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.; Bhan, Ishir] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Quraishi, SA (reprint author), Harvard Univ, Sch Med, Boston, MA USA. EM squraishi@mgh.harvard.edu FU National Institutes of Health (NIH) [T32 GM007592, L30 TR001257]; NIH [P50GM02700, 1, 4, R01 HL119344, R01 AI093723, U01 AI087881, K23 DK081677]; American Thoracic Society Foundation; American Thoracic Society FX Dr. Quraishi received support for article research from the National Institutes of Health (NIH) (grants T32 GM007592 and L30 TR001257) and departmental funding. His institution received grant support from the NIH. Dr. Kaneki received support for article research from the NIH (grant P50GM02700). His institution received grant support from the NIH (projects 1 and 4). Dr. Bajwa received support for article research from the American Thoracic Society Foundation and the NIH (grant R01 HL119344). His institution received grant support from the NIH and the American Thoracic Society. Dr. Camargo received support for article research from the NIH (grants R01 AI093723 and U01 AI087881). His institution received grant support from the NIH. Dr. Bhan received support for article research from the NIH (grant K23 DK081677). The remaining authors have disclosed that they do not have any potential conflicts of interest. NR 74 TC 7 Z9 8 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 2015 VL 43 IS 9 BP 1928 EP 1937 DI 10.1097/CCM.0000000000001148 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA DC5JH UT WOS:000369256800039 PM 26086941 ER PT J AU Teo, EP Teoh, JG Hung, J AF Teo, Eliza P. Teoh, Jonathan G. Hung, Judy TI Mitral valve and papillary muscle abnormalities in hypertrophic obstructive cardiomyopathy SO CURRENT OPINION IN CARDIOLOGY LA English DT Review DE hypertrophic obstructive cardiomyopathy; mitral valve; papillary muscles; systolic anterior motion ID OUTFLOW TRACT OBSTRUCTION; CARDIOVASCULAR MAGNETIC-RESONANCE; SYSTOLIC ANTERIOR MOTION; SURGICAL OUTCOMES; SEPTAL MYECTOMY; MECHANISM; LEAFLET; ECHOCARDIOGRAPHY; REGURGITATION; ASSOCIATION AB Purpose of review This section reviews abnormalities of the mitral valve apparatus that are associated with hypertrophic obstructive cardiomyopathy. Recent findings Mitral valve abnormalities in hypertrophic obstructive cardiomyopathy include leaflet elongation and thickening and hypertrophy with anterior displacement of the papillary muscles. This combination contributes to the development of systolic anterior motion. The resultant flow forces during systolic anterior motion pulling the leaflets into the left ventricular outflow tract also result in reduced leaflet coaptation and a posteriorly directed mitral regurgitant jet. Additional mitral valve abnormalities include degenerative leaflet changes, aberrant chordal attachments and papillary muscle anomalies. Summary Mitral valve abnormalities are common in hypertrophic obstructive cardiomyopathy and play an important role in the pathophysiology of dynamic left ventricular outflow tract obstruction. C1 [Teo, Eliza P.; Teoh, Jonathan G.; Hung, Judy] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02115 USA. RP Hung, J (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. EM jhung@mgh.harvard.edu NR 25 TC 2 Z9 3 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0268-4705 EI 1531-7080 J9 CURR OPIN CARDIOL JI Curr. Opin. Cardiol. PD SEP PY 2015 VL 30 IS 5 BP 475 EP 482 DI 10.1097/HCO.0000000000000200 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DD0FA UT WOS:000369594600003 PM 26192489 ER PT J AU Wasfy, MM Weiner, RB AF Wasfy, Meagan M. Weiner, Rory B. TI Differentiating the athlete's heart from hypertrophic cardiomyopathy SO CURRENT OPINION IN CARDIOLOGY LA English DT Review DE athlete's heart; exercise; left ventricular remodeling; myocardial function ID LEFT-VENTRICULAR HYPERTROPHY; CARDIOVASCULAR-DISEASE; MYOCARDIAL FIBROSIS; MAGNETIC-RESONANCE; CARDIAC STRUCTURE; WALL THICKNESS; GRAY ZONE; EXERCISE; ECHOCARDIOGRAPHY; PARTICIPATION AB Purpose of review Exercise-induced cardiac remodeling (EICR), or athlete's heart, refers to the cardiac structural and functional adaptations to exercise training. Although the degree of physiological left ventricular hypertrophy (LVH) is typically mild in trained athletes, in some LVH is substantial enough to prompt concern for hypertrophic cardiomyopathy (HCM). This review summarizes the available imaging tools to help make this important clinical distinction. Recent findings Advanced echocardiographic techniques (tissue and Doppler and speckle tracking) and cardiac magnetic resonance imaging are being investigated to aid in the differentiation of EICR and HCM in 'gray-zone' hypertrophy cases. Higher early diastolic (E') velocity by tissue Doppler imaging has been documented in athletes. HCM patients have been found to have lower global longitudinal strain (GLS) when compared with athletes with LVH. Analysis of twisting and untwisting of the LV with speckle tracking may also help distinguish athlete's heart from HCM. Studies of the expected degree and time course of LVH regression after exercise cessation (in the setting of prescribed detraining) are needed as this may be a useful adjunct to determine the cause of LVH in particularly challenging cases. Summary Ongoing research with novel imaging techniques continues to improve the ability to distinguish athlete's heart from HCM in situations of 'gray-zone' hypertrophy. C1 [Wasfy, Meagan M.; Weiner, Rory B.] Massachusetts Gen Hosp, Div Cardiol, Cardiovasc Performance Program, Yawkey Suite 5B,55 Fruit St, Boston, MA 02114 USA. RP Weiner, RB (reprint author), Massachusetts Gen Hosp, Div Cardiol, Cardiovasc Performance Program, Yawkey Suite 5B,55 Fruit St, Boston, MA 02114 USA. EM rweiner@partners.org NR 39 TC 3 Z9 3 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0268-4705 EI 1531-7080 J9 CURR OPIN CARDIOL JI Curr. Opin. Cardiol. PD SEP PY 2015 VL 30 IS 5 BP 500 EP 505 DI 10.1097/HCO.0000000000000203 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DD0FA UT WOS:000369594600006 PM 26196658 ER PT J AU Sahora, K Castillo, CFD AF Sahora, Klaus Castillo, Carlos Fernandez-del TI Intraductal papillary mucinous neoplasms SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Review DE cancer; cystic; IPMN; mucinous; observation; pancreas; surgery ID INTERNATIONAL-CONSENSUS-GUIDELINES; PANCREATIC DUCTAL ADENOCARCINOMA; FINE-NEEDLE-ASPIRATION; ENDOSCOPIC ULTRASOUND; EXTRAPANCREATIC NEOPLASMS; EPITHELIAL SUBTYPES; CYSTIC NEOPLASMS; RISK-ASSESSMENT; GNAS MUTATIONS; FOLLOW-UP AB Purpose of review Our understanding of intraductal papillary mucinous neoplasm (IPMN) of the pancreas has remarkably grown within the last decade; nonetheless there is still an ongoing controversy if the majority of these potentially malignant neoplasms need to be resected or if observation in a subset is well tolerated. Recent findings Novel cyst fluid biomarkers, like Gnas mutations or mab DAS-1, could play a pivotal role in the distinction of IPMN vs. other cystic lesions, in the sub-classification of IPMN and in the detection of IPMN with high-grade dysplasia or invasive cancer. Other recent studies focused on natural history of minimal-and extensive-mixed IPMN and the safety of the 2012 AIP guidelines. Small series also described that observation can be an option in selected frail patients with MD-IPMN. Further, data from a large European multicenter study analysis indicated that patients with IPMN do not have an increased frequency of extrapancreatic malignancies. Summary Increasing knowledge about the nature of IPMN and their subtypes has resulted in an individualized approach in diagnosis and treatment. Owing to the availability of accurate diagnostic instruments, timing and indication for pancreatic resection have become more selective, sparing patients with harmless IPMN from major surgery. C1 [Sahora, Klaus] Med Univ Vienna, Dept Surg, Vienna, Austria. [Castillo, Carlos Fernandez-del] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Castillo, Carlos Fernandez-del] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Castillo, CFD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Wang Ambulatory Care Ctr 460, 15 Parkman St, Boston, MA 02114 USA. EM CFERNANDEZ@mgh.harvard.edu NR 62 TC 5 Z9 5 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0267-1379 EI 1531-7056 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD SEP PY 2015 VL 31 IS 5 BP 424 EP 429 DI 10.1097/MOG.0000000000000198 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DD0EP UT WOS:000369593500012 PM 26125316 ER PT J AU Zhou, ES Falk, SJ Bober, SL AF Zhou, Eric S. Falk, Sandy J. Bober, Sharon L. TI Managing premature menopause and sexual dysfunction SO CURRENT OPINION IN SUPPORTIVE AND PALLIATIVE CARE LA English DT Review DE breast cancer; quality of life; sexual function; sexual health; young women ID QUALITY-OF-LIFE; BREAST-CANCER SURVIVORS; BODY-IMAGE; OVARIAN SUPPRESSION; VAGINAL ATROPHY; FOLLOW-UP; WOMEN; THERAPY; RECONSTRUCTION; MASTECTOMY AB Purpose of review Young women (<45 years of age) diagnosed with breast cancer face increased risk of sexual dysfunction as a result of their cancer-directed treatment. We will review the recent literature examining this critical challenge and discuss current efforts to address sexual dysfunction. Recent findings In the period since 2013, the literature has focused on sexual issues that result from the premature onset of menopausal symptoms and changes in sexual health following breast surgery. The impact of premature menopause in young women with breast cancer is profound and can affect all aspects of the sexual experience, from desire to function, and quality of life. Furthermore, the surgical treatment of breast cancer also has significant implications with respect to sexual desire and body image. There is a paucity of sexual health intervention for this population, though recent efforts suggest that sexual health outcomes may be improved if women are offered the appropriate intervention opportunities. However, the sexual function of young breast cancer patients is an under-discussed and under-treated health issue that warrants greater research and clinical focus. Summary Further intervention trials must be completed in this population of young women for whom sexual function plays such a critical role in their personal and relationship well being. C1 [Zhou, Eric S.; Falk, Sandy J.; Bober, Sharon L.] Dana Farber Canc Inst, Shields Warren 320,450 Brookline Ave, Boston, MA 02215 USA. [Zhou, Eric S.; Falk, Sandy J.; Bober, Sharon L.] Harvard Univ, Sch Med, Boston, MA USA. RP Bober, SL (reprint author), Dana Farber Canc Inst, Shields Warren 320,450 Brookline Ave, Boston, MA 02215 USA. EM sharon_bober@dfci.harvard.edu NR 62 TC 1 Z9 1 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1751-4258 EI 1751-4266 J9 CURR OPIN SUPPORT PA JI Curr. Opin Support Palliat. Car. PD SEP PY 2015 VL 9 IS 3 BP 294 EP 300 DI 10.1097/SPC.0000000000000156 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DD1YT UT WOS:000369720100017 PM 26155020 ER PT J AU Iyer, SP Jones, A Talamantes, E Barnert, ES Kanzaria, HK Detz, A Daskivich, TJ Jones, L Ryan, GW Mahajan, AP AF Iyer, Sharat P. Jones, Andrea Talamantes, Efrain Barnert, Elizabeth S. Kanzaria, Hemal K. Detz, Alissa Daskivich, Timothy J. Jones, Loretta Ryan, Gery W. Mahajan, Anish P. TI IMPROVING HEALTH CARE FOR THE FUTURE UNINSURED IN LOS ANGELES COUNTY: A COMMUNITY-PARTNERED DIALOGUE SO ETHNICITY & DISEASE LA English DT Article DE Medically Uninsured; Patient Protection and Affordable Care Act; Health Services Accessibility; Community Health Services ID PARTICIPATORY RESEARCH; ENGAGEMENT; SERVICES; ACT AB Objectives: To understand the health care access issues faced by Los Angeles (LA) County's uninsured and residually uninsured after implementation of the Affordable Care Act (ACA) and to identify potential solutions using a community-partnered dialogue. Design: Qualitative study using a community-partnered participatory research framework. Setting: Community forum breakout discussion. Discussants: Representatives from LA County health care agencies, community health care provider organizations, local community advocacy and service organizations including uninsured individuals, and the county school district. Main Outcome Measures: Key structural and overarching value themes identified through community-partnered pile sort, c-coefficients measuring overlap between themes. Results: Five overarching value themes were identified - knowledge, trust, quality, partnership, and solutions. Lack of knowledge and misinformation were identified as barriers to successful enrollment of the eligible uninsured and providing health care to undocumented individuals. Discussants noted dissatisfaction with the quality of traditional sources of health care and a broken cycle of trust and disengagement. They also described inherent trust by the uninsured in "outsider" community-based providers not related to quality. Conclusions: Improving health care for the residually uninsured after ACA implementation will require addressing dissatisfaction in safety-net providers, disseminating knowledge and providing health care through trusted nontraditional sources, and using effective and trusted partnerships between community and health care agencies with mutual respect. Community-academic partnerships can be a trusted conduit to discuss issues related to the health care of vulnerable populations. C1 [Iyer, Sharat P.; Talamantes, Efrain; Barnert, Elizabeth S.; Kanzaria, Hemal K.; Daskivich, Timothy J.] Univ Calif Los Angeles, Robert Wood Johnson Fdn Clin Scholars, Los Angeles, CA 90024 USA. [Iyer, Sharat P.] James J Peters VA Med Ctr, VISN3 Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. [Iyer, Sharat P.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Jones, Andrea; Jones, Loretta] Charles R Drew Univ Med & Sci, 1621 E 120th St, Los Angeles, CA 90059 USA. [Jones, Andrea; Jones, Loretta] Hlth African Amer Families, Los Angeles, CA USA. [Talamantes, Efrain; Detz, Alissa] Univ Calif Los Angeles, Natl Res Serv Award GIM Fellowship Primary Care &, Los Angeles, CA 90024 USA. [Kanzaria, Hemal K.] Univ Calif Los Angeles, Dept Pediat, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Kanzaria, Hemal K.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RAND Corp, Los Angeles, CA USA. [Ryan, Gery W.; Mahajan, Anish P.] Los Angeles Cty Dept Hlth Serv, Los Angeles, CA USA. [Mahajan, Anish P.] Univ Calif Los Angeles, Div Gen Internal Med, Los Angeles, CA 90024 USA. [Mahajan, Anish P.] Univ Calif Los Angeles, Hlth Serv Res, Los Angeles, CA 90024 USA. RP Iyer, SP (reprint author), James J Peters VA Med Ctr MIRECC OOMH, 130 W Kingsbridge Rd,Room 6A-44, Bronx, NY 10468 USA. EM Sharat.Iyer@mssm.edu FU Robert Wood Johnson Foundation Clinical Scholars program; Ruth L. Kirschstein National Research Service Award Institutional Training Grant [T32HP19001]; US Department of Veterans Affairs FX The authors would like to acknowledge the contributions of the many community partners who participated in the community forum and in the production of this manuscript. We also thank the faculty and program staff of the Robert Wood Johnson Foundation Clinical Scholars and the National Research Service Award General Internal Medicine Fellowship at UCLA, especially Dr. Kenneth Wells. Funding for this study was provided by the Robert Wood Johnson Foundation Clinical Scholars program, the Ruth L. Kirschstein National Research Service Award Institutional Training Grant #T32HP19001, and the US Department of Veterans Affairs. This material is the result of work supported with resources and the use of facilities at the James J. Peters VA Medical Center, Bronx, NY, and the West Los Angeles VA Medical Center, Los Angeles, CA. 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 13 TC 0 Z9 0 U1 2 U2 5 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X EI 1945-0826 J9 ETHNIC DIS JI Ethn. Dis. PD FAL PY 2015 VL 25 IS 4 BP 487 EP 494 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DC9CA UT WOS:000369517100016 PM 26675541 ER PT J AU Manuel, JK Satre, DD Tsoh, J Moreno-John, G Ramos, JS McCance-Katz, EF Satterfield, JM AF Manuel, Jennifer K. Satre, Derek D. Tsoh, Janice Moreno-John, Gina Ramos, Jacqueline S. McCance-Katz, Elinore F. Satterfield, Jason M. TI Adapting Screening, Brief Intervention, and Referral to Treatment for Alcohol and Drugs to Culturally Diverse Clinical Populations SO JOURNAL OF ADDICTION MEDICINE LA English DT Review DE Alcohol; cultural competence; motivational interviewing; SBIRT; substance use disorders ID SUBSTANCE-ABUSE TREATMENT; DISORDERS IDENTIFICATION TEST; CITY EMERGENCY-DEPARTMENT; OF-VETERANS-AFFAIRS; PRIMARY-CARE; MEXICAN-AMERICANS; MOTIVATIONAL INTERVENTIONS; SERVICE UTILIZATION; METHADONE TREATMENT; ETHNIC-DIFFERENCES AB Objectives: To review the literature on the screening, brief intervention, and referral to treatment (SBIRT) approach to alcohol and drug use with racial and ethnic subgroups in the United States and to develop recommendations for culturally competent SBIRT practice. Methods: Articles reporting on the use of SBIRT components (screening, brief intervention, referral to treatment) for alcohol and drug use were identified through a comprehensive literature search of PubMed from 1995 to 2015. Results: A synthesis of the published literature on racial and ethnic considerations regarding SBIRT components (including motivational interviewing techniques) was created using evidence-based findings. Recommendations on culturally competent use of SBIRT with specific ethnic groups are also described. Conclusions: On the basis of the literature reviewed, SBIRToffers a useful set of tools to help reduce risky or problematic substance use. Special attention to validated screeners, appropriate use of language/ literacy, trust building, and incorporation of patient and community health care preferences may enhance SBIRT acceptability and effectiveness. Practice Implications: Providers should consider the implications of previous research when adapting SBIRT for diverse populations, and use validated screening and brief intervention methods. The accompanying case illustration provides additional information relevant to clinical practice. C1 [Manuel, Jennifer K.] San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. [Satre, Derek D.; Tsoh, Janice; Ramos, Jacqueline S.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Satre, Derek D.] Kaiser Permanente Northern Calif Reg, Div Res, Oakland, CA USA. [Moreno-John, Gina; Satterfield, Jason M.] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94143 USA. [McCance-Katz, Elinore F.] Subst Abuse & Mental Hlth Serv Adm, Rockville, MD USA. RP Manuel, JK (reprint author), San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. EM Jennifer.manuel@va.gov FU SAMHSA/CSAT [U79T1020295]; NIHNIDA [P50DA09253, U10DA015815] FX This study was supported by grant U79T1020295 from SAMHSA/CSAT awarded to Dr Satterfield, and was also supported by NIHNIDA Grants P50DA09253 (PI = Joseph Guydish; joseph.guydish@ucsf.edu), U10DA015815 (PI = James Sorensen; james.Sorensen@ucsf.edu). NR 64 TC 3 Z9 3 U1 7 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1932-0620 EI 1935-3227 J9 J ADDICT MED JI J. Addict. Med. PD SEP-OCT PY 2015 VL 9 IS 5 BP 343 EP 351 DI 10.1097/ADM.0000000000000150 PG 9 WC Substance Abuse SC Substance Abuse GA DC9CK UT WOS:000369518300001 PM 26428359 ER PT J AU Satre, DD Manuel, JK Larios, S Steiger, S Satterfield, J AF Satre, Derek D. Manuel, Jennifer K. Larios, Sandra Steiger, Scott Satterfield, Jason TI Cultural Adaptation of Screening, Brief Intervention and Referral to Treatment Using Motivational Interviewing SO JOURNAL OF ADDICTION MEDICINE LA English DT Editorial Material DE alcohol; cultural competence; hazardous drinking; motivational interviewing; SBIRT; substance use disorder ID PRIMARY-CARE; DRUG-USE; TREATMENT SBIRT; CLINICAL-TRIAL; ILLICIT DRUG; ALCOHOL-USE; ACCULTURATION; CALIFORNIA; CESSATION; DRINKING AB This clinical case presentation and discussion illustrates a culturally adapted alcohol and drug use intervention using the Screening, Brief Intervention, and Referral to Treatment (SBIRT) approach, incorporating motivational interviewing skills. This case conference serves to complement the accompanying review article on SBIRT with diverse cultural groups, placing information from the reviewin the context of a typical clinical setting. In this example, SBIRTis provided in a primary care clinic to a Latino patient who reports hazardous drinking, depression, chronic pain and use of prescription opioids. C1 [Satre, Derek D.] Univ Calif San Francisco, Dept Psychiat, 401 Parnassus Ave,Box 0984, San Francisco, CA 94143 USA. [Satre, Derek D.] Kaiser Permanente Northern Calif Reg, Div Res, Oakland, CA USA. [Manuel, Jennifer K.] San Francisco VA Med Ctr, San Francisco, CA USA. [Larios, Sandra] San Francisco Gen Hosp, Dept Psychiat, San Francisco, CA USA. [Steiger, Scott; Satterfield, Jason] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94143 USA. RP Satre, DD (reprint author), Univ Calif San Francisco, Dept Psychiat, 401 Parnassus Ave,Box 0984, San Francisco, CA 94143 USA. EM dereks@lppi.ucsf.edu FU NIDA NIH HHS [T32 DA007250, P50DA09253, P50 DA009253, U10 DA015815, U10DA015815] NR 35 TC 1 Z9 1 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1932-0620 EI 1935-3227 J9 J ADDICT MED JI J. Addict. Med. PD SEP-OCT PY 2015 VL 9 IS 5 BP 352 EP 357 DI 10.1097/ADM.0000000000000149 PG 6 WC Substance Abuse SC Substance Abuse GA DC9CK UT WOS:000369518300002 PM 26428360 ER PT J AU Jones, AL Hanusa, BH Appelt, CJ Haas, GL Gordon, AJ Hausmann, LRM AF Jones, Audrey L. Hanusa, Barbara H. Appelt, Cathleen J. Haas, Gretchen L. Gordon, Adam J. Hausmann, Leslie R. M. TI Racial Differences in Veterans' Satisfaction With Addiction Treatment Services SO JOURNAL OF ADDICTION MEDICINE LA English DT Article DE healthcare disparities; patient satisfaction; substance abuse treatment services ID SUBSTANCE-ABUSE TREATMENT; HEALTH-CARE; PATIENT-SATISFACTION; UNITED-STATES; TREATMENT COMPLETION; OUTPATIENT TREATMENT; ETHNIC DISPARITIES; OUTCOMES; RACE/ETHNICITY; PERCEPTIONS AB Objectives: Racial minorities experience lower rates of alcohol treatment completion than whites. Treatment satisfaction is an important factor in alcohol treatment retention, yet few studies have explored the satisfaction of racial minorities while in treatment. This study examined racial differences in addiction treatment satisfaction and explored factors that might mediate or moderate racial differences in satisfaction. Methods: We surveyed non-Hispanic black and non-Hispanic white veterans with an alcohol-related diagnosis about addiction treatment services at a large Veterans Affairs medical center. Treatment satisfaction was measured using the 8-item Client Satisfaction Questionnaire, dichotomized as low versus non-low satisfaction in analyses. The chi(2) and logistic regression methods were used to test for associations of race and sociodemographic characteristics with treatment satisfaction. Results: Among 271 black and 304 white veterans with an alcohol-related diagnosis, race was not statistically associated with treatment satisfaction in bivariate analyses (P > 0.05). However, we identified significant interactions of race with mental health diagnoses in predicting treatment satisfaction in multivariable analyses (adj odds ratio = 0.55; 95% confidence interval [CI] = 0.39-0.78). In post hoc comparisons among veterans with zero mental health diagnoses, black veterans had a greater probability of reporting low satisfaction than whites (marginal difference = 0.13; 95% CI = 0.04-0.22). In veterans with 4 or more diagnoses, whites had a greater probability than blacks of reporting low satisfaction (marginal difference = 0.28, 95% CI = 0.10-0.46). Regardless of race, past homelessness was associated with low satisfaction (adj odds ratio = 2.09; 95% CI = 1.19-3.67). Conclusions: Racial minorities, veterans with unstable housing, and white veterans with co-occurring mental health disorders may be at risk of experiencing low treatment satisfaction. C1 [Jones, Audrey L.; Gordon, Adam J.; Hausmann, Leslie R. M.] Vet Affairs Pittsburgh Healthcare Syst, VA Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Hanusa, Barbara H.; Appelt, Cathleen J.; Haas, Gretchen L.] Vet Affairs Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA. [Appelt, Cathleen J.] Duquesne Univ, Dept Sociol, Pittsburgh, PA 15219 USA. [Haas, Gretchen L.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Gordon, Adam J.; Hausmann, Leslie R. M.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. RP Jones, AL (reprint author), VAPHS, VA Ctr Hlth Equ Res & Promot CHERP, Univ Dr,151C,Bldg 30, Pittsburgh, PA 15240 USA. EM Audrey.Jones3@va.gov FU Department of Veterans Affairs Substance Use Disorder Quality Enhancement Research Initiative [SUDQ-LIP1411]; VISN4 Mental Illness Research, Education and Clinical Center at the Veterans Affairs Pittsburgh Healthcare System FX Supported by the Department of Veterans Affairs Substance Use Disorder Quality Enhancement Research Initiative (SUDQ-LIP1411) and the VISN4 Mental Illness Research, Education and Clinical Center at the Veterans Affairs Pittsburgh Healthcare System. NR 41 TC 1 Z9 1 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1932-0620 EI 1935-3227 J9 J ADDICT MED JI J. Addict. Med. PD SEP-OCT PY 2015 VL 9 IS 5 BP 383 EP 390 DI 10.1097/ADM.0000000000000144 PG 8 WC Substance Abuse SC Substance Abuse GA DC9CK UT WOS:000369518300006 PM 26335005 ER PT J AU McLellan, DL Caban-Martinez, AJ Nelson, CC Pronk, NP Katz, JN Allen, JD Davis, KL Wagner, GR Sorensen, G AF McLellan, Deborah L. Caban-Martinez, Alberto J. Nelson, Candace C. Pronk, Nicolaas P. Katz, Jeffrey N. Allen, Jennifer D. Davis, Kia L. Wagner, Gregory R. Sorensen, Glorian TI Organizational Characteristics Influence Implementation of Worksite Health Protection and Promotion Programs Evidence From Smaller Businesses SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID OCCUPATIONAL-SAFETY; UNITED-STATES; WORKPLACE; READINESS; EMPLOYERS; SECTOR; SITE AB Objective: We explored associations between organizational factors (size, sector, leadership support, and organizational capacity) and implementation of occupational safety and health (OSH) and worksite health promotion (WHP) programs in smaller businesses. Methods: We conducted a webbased survey of human resource managers of 117 smaller businesses (<750 employees) and analyzed factors associated with implementation of OSH and WHP among these sites using multivariate analyses. Results: Imple-Implementation of OSH, but not WHP activities, was related to industry sector (P = 0.003). Leadership support was positively associated with OSH activities (P < 0.001), but negatively associated with WHP implementation. Organizational capacity (budgets, staffing, and committee involvement) was associated with implementation of both OSH and WHP. Size was related to neither. Conclusions: Leadership support and specifically allocated resources reflecting that support are important factors for implementing OSH and WHP in smaller organizations. C1 [McLellan, Deborah L.; Nelson, Candace C.; Allen, Jennifer D.; Davis, Kia L.; Sorensen, Glorian] Dana Farber Canc Inst, Boston, MA 02215 USA. [McLellan, Deborah L.; Caban-Martinez, Alberto J.; Nelson, Candace C.; Pronk, Nicolaas P.; Katz, Jeffrey N.; Allen, Jennifer D.; Davis, Kia L.; Wagner, Gregory R.; Sorensen, Glorian] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Caban-Martinez, Alberto J.] Univ Miami, Sch Med, Miami, FL USA. [Pronk, Nicolaas P.] HealthPartners Inc, Minneapolis, MN USA. [Katz, Jeffrey N.] Brigham & Womens Hosp, Boston, MA USA. [Allen, Jennifer D.] Tufts Univ, Medford, MA 02155 USA. [Wagner, Gregory R.] NIOSH, CDC, Washington, DC USA. RP McLellan, DL (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 450 Brookline Ave,LW715, Boston, MA 02215 USA. EM deborah_mclellan@dfci.harvard.edu RI Allen, Jennifer/M-2113-2015; OI Davis, Kia/0000-0002-1338-3018 FU National Institute for Occupational Safety and Health [U19 OH008861]; National Institutes of Health [K05 CA108663, R25 CA057711, 5R25 GM055353] FX This work was supported by a grant from the National Institute for Occupational Safety and Health (U19 OH008861) for the Harvard School of Public Health Center for Work, Health and Well-being, and grants from the National Institutes of Health (K05 CA108663 to GS; R25 CA057711 and 5R25 GM055353 to KD). NR 42 TC 6 Z9 6 U1 2 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 SEP PY 2015 VL 57 IS 9 BP 1009 EP 1016 DI 10.1097/JOM.0000000000000517 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DC8AH UT WOS:000369441800013 PM 26340290 ER PT J AU Williams, JAR Nelson, CC Caban-Martinez, AJ Katz, JN Wagner, GR Pronk, NP Sorensen, G McLellan, DL AF Williams, Jessica A. R. Nelson, Candace C. Caban-Martinez, Alberto J. Katz, Jeffrey N. Wagner, Gregory R. Pronk, Nicolaas P. Sorensen, Glorian McLellan, Deborah L. TI Validation of a New Metric for Assessing the Integration of Health Protection and Health Promotion in a Sample of Small- and Medium-Sized Employer Groups SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID OCCUPATIONAL-SAFETY; WELLWORKS PROJECT; BEHAVIOR-CHANGE; PROGRAM; WORK AB Objective: To conduct validation analyses for a new measure of the integration of worksite health protection and health promotion approaches developed in earlier research. Methods: A survey of small-to medium-sized employers located in the United States was conducted between October 2013 and March 2014 (n = 111). Cronbach a coefficient was used to assess reliability, and Pearson correlation coefficients were used to assess convergent validity. Results: The integration score was positively associated with the measures of occupational safety and health and health promotion activities/ policies-supporting its convergent validity (Pearson correlation coefficients of 0.32 to 0.47). Cronbach a coefficient was 0.94, indicating excellent reliability. Conclusions: The integration score seems to be a promising tool for assessing integration of health promotion and health protection. Further work is needed to test its dimensionality and validate its use in other samples. C1 [Williams, Jessica A. R.; Nelson, Candace C.; Sorensen, Glorian; McLellan, Deborah L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Williams, Jessica A. R.; Nelson, Candace C.; Caban-Martinez, Alberto J.; Katz, Jeffrey N.; Wagner, Gregory R.; Pronk, Nicolaas P.; Sorensen, Glorian; McLellan, Deborah L.] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Caban-Martinez, Alberto J.] Univ Miami, Sch Med, Coral Gables, FL 33124 USA. [Pronk, Nicolaas P.] HealthPartners Inc, Minneapolis, MN USA. [Katz, Jeffrey N.] Brigham & Womens Hosp, Boston, MA USA. [Wagner, Gregory R.] NIOSH, Washington, DC USA. RP Williams, JAR (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Ctr Populat & Dev Studies, 9 Bow St, Cambridge, MA 02138 USA. EM jwilliams@hsph.harvard.edu FU National Institute for Occupational Safety and Health [U19 OH008861]; Robert Wood Johnson Foundation FX This work was supported by a grant from the National Institute for Occupational Safety and Health (U19 OH008861) for the Harvard T. H. Chan School of Public Health Center for Work, Health and Well-being. Dr Williams is also supported by the Robert Wood Johnson Foundation. NR 21 TC 6 Z9 6 U1 1 U2 2 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 SEP PY 2015 VL 57 IS 9 BP 1017 EP 1021 DI 10.1097/JOM.0000000000000521 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DC8AH UT WOS:000369441800014 PM 26340291 ER PT J AU Xu, JJ Liu, ZG Mashaghi, A Sun, XH Lu, Y Li, YM Wu, D Yang, YJ Wei, AJ Zhao, YJ Lu, C Hong, JX AF Xu, Jianjiang Liu, Zuguo Mashaghi, Alireza Sun, Xinghuai Lu, Yi Li, Yimin Wu, Dan Yang, Yujing Wei, Anji Zhao, Yujin Lu, Chun Hong, Jiaxu TI Novel Therapy for Primary Canaliculitis A Pilot Study of Intracanalicular Ophthalmic Corticosteroid/Antibiotic Combination Ointment Infiltration SO MEDICINE LA English DT Article ID MANAGEMENT; SUSCEPTIBILITY; ANTIBIOTICS; ACTINOMYCES; DIAGNOSIS AB In patients with primary canaliculitis, conservative medical therapy is associated with a high recurrence rate. Surgical treatments carry a great resolution rate but sometimes can result in the lacrimal pump dysfunction and canalicular scarring. The aim of this study is to introduce a minimally invasive approach, intracanalicular ophthalmic corticosteroid/antibiotic combination ointment infiltration (IOI, intracanalicular ointment infiltration), and to report our preliminary results for treating primary canaliculitis.In this retrospective, interventional case series, 68 consecutive patients with newly developed primary canaliculitis at a major tertiary eye center between January 2012 and January 2015. Thirty-six patients received conservative medical treatment alone (group 1; 36 eyes). Twenty-two patients and 10 medically uncontrolled patients from group 1 underwent IOI therapy (group 2; 32 eyes). Ten patients and 26 recurrent patients from group 1 and group 2 underwent surgery (group 3; 36 eyes). Patients were followed-up for at least 8 weeks. Clinical characteristics and outcomes were analyzed and compared.In this study, patients' age, sex, onset location, and durations of disease among 3 groups showed no significant difference. The resolution rate in group 2 was 72.7% (16/22) for new patients and 68.8% (22/32) for gross patients, respectively, both of which are higher than that of group 1 (22.2%, 10/36) but lower than that of group 3 (100%, 36/36). Of group 3, 2 patients received 2 surgical interventions and resolved finally. Microbiological workup was available in 51 patients. The most common isolates were staphylococcus species (27.9%) and streptococcus species (20%). Canalicular laceration developed in 1 patient during the IOI procedure and 1 patient undergoing surgery. Only 2 had postoperative lacrimal pump dysfunction and 1 had canalicular scarring in group 3.The IOI may be an effective and minimally invasive technique for treating primary canaliculitis and obviate the need for further intensive surgery. C1 [Xu, Jianjiang; Sun, Xinghuai; Lu, Yi; Li, Yimin; Wu, Dan; Yang, Yujing; Wei, Anji; Zhao, Yujin; Lu, Chun; Hong, Jiaxu] Fudan Univ, Shanghai Med Coll, Dept Ophthalmol & Visual Sci, Eye & ENT Hosp, Shanghai 200433, Peoples R China. [Liu, Zuguo; Hong, Jiaxu] Xiamen Univ, Sch Life Sci, Fujian Prov Key Lab Ophthalmol & Visual Sci, Xiamen, Fujian, Peoples R China. [Mashaghi, Alireza; Hong, Jiaxu] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Sun, Xinghuai] Natl Hlth & Family Planning Commiss, Key Lab Myopia, Shanghai, Peoples R China. RP Hong, JX (reprint author), Fudan Univ, Shanghai 200433, Peoples R China. EM jiaxu_hong@163.com FU Ministry of Health, China [201302015]; National Science and Technology Research Program; Ministry of Science and Technology, China [2012BAI08B01]; National Natural Science Foundation of China [81170817, 81200658, 81300735, 81270978, U1205025, 81330022]; Scientific Research Program, Science and Technology Commission of Shanghai Municipality, Shanghai [13441900900, 13430720400]; Chinese Postdoctoral Fund [XMU135890]; New Technology Joint Research Project in Shanghai Hospitals [SHDC12014114]; Key Clinic Medicine Research Program FX the authors were supported by grants from the Key Clinic Medicine Research Program, the Ministry of Health, China (201302015); the National Science and Technology Research Program, the Ministry of Science and Technology, China (2012BAI08B01); the National Natural Science Foundation of China (81170817, 81200658, 81300735, 81270978, U1205025, and 81330022); the Scientific Research Program, Science and Technology Commission of Shanghai Municipality, Shanghai (13441900900, 13430720400); the Chinese Postdoctoral Fund (XMU135890); and the New Technology Joint Research Project in Shanghai Hospitals (SHDC12014114). The sponsor or funding organization had no role in the design or conduct of this research. NR 19 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 0025-7974 EI 1536-5964 J9 MEDICINE JI Medicine (Baltimore) PD SEP PY 2015 VL 94 IS 39 AR e1611 DI 10.1097/MD.0000000000001611 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA DC9IK UT WOS:000369534600044 PM 26426646 ER PT J AU Kaunitz, AM Kaunitz, JD AF Kaunitz, Andrew M. Kaunitz, Jonathan D. TI Compounded bioidentical hormone therapy: time for a reality check? SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID UNITED-STATES C1 [Kaunitz, Andrew M.] Univ Florida, Coll Med, Dept Obstet & Gynecol, Jacksonville, FL USA. [Kaunitz, Jonathan D.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Kaunitz, Jonathan D.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Kaunitz, Jonathan D.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. RP Kaunitz, AM (reprint author), Univ Florida, Coll Med, Dept Obstet & Gynecol, Jacksonville, FL USA. FU NIDDK NIH HHS [R01 DK054221] NR 6 TC 0 Z9 0 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD SEP PY 2015 VL 22 IS 9 BP 919 EP 920 DI 10.1097/GME.0000000000000484 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DD0IL UT WOS:000369603500001 PM 26035149 ER PT J AU Papayannidis, C DeAngelo, DJ Stock, W Huang, B Shaik, MN Cesari, R Zheng, X Reynolds, JM English, PA Ozeck, M Aster, JC Kuo, F Huang, D Lira, PD McLachlan, KR Kern, KA Garcia-Manero, G Martinelli, G AF Papayannidis, C. DeAngelo, D. J. Stock, W. Huang, B. Shaik, M. N. Cesari, R. Zheng, X. Reynolds, J. M. English, P. A. Ozeck, M. Aster, J. C. Kuo, F. Huang, D. Lira, P. D. McLachlan, K. R. Kern, K. A. Garcia-Manero, G. Martinelli, G. TI A Phase 1 study of the novel gamma-secretase inhibitor PF-03084014 in patients with T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma SO BLOOD CANCER JOURNAL LA English DT Letter ID PATHWAYS; NOTCH C1 [Papayannidis, C.; Martinelli, G.] Univ Bologna, Dept Expt Diagnost & Specialty Med, Bologna, Italy. [DeAngelo, D. J.] Dana Farber Canc Inst, Adult Leukemia Inst, Boston, MA 02115 USA. [Stock, W.] Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. [Huang, B.] Pfizer Oncol, Groton, CT USA. [Shaik, M. N.; Zheng, X.; Reynolds, J. M.; English, P. A.; Ozeck, M.; Huang, D.; Lira, P. D.; McLachlan, K. R.; Kern, K. A.] Pfizer Oncol, San Diego, CA USA. [Cesari, R.] Pfizer Oncol, Milan, Italy. [Aster, J. C.; Kuo, F.] Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. [Garcia-Manero, G.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. RP Papayannidis, C (reprint author), Univ Bologna, Dept Expt Diagnost & Specialty Med, Bologna, Italy. EM martg@tin.it NR 15 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2044-5385 J9 BLOOD CANCER J JI Blood Cancer J. PD SEP PY 2015 VL 5 AR e350 DI 10.1038/bcj.2015.80 PG 3 WC Oncology SC Oncology GA DC0PE UT WOS:000368919100004 PM 26407235 ER PT J AU Camargo, CA Roosevelt, T AF Camargo, Carlos A., Jr. Roosevelt, Tweed TI The Misunderstood Asthma of Theodore Roosevelt SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE LA English DT Article DE Asthma; Biography; History; Psychology; Theodore Roosevelt AB In this special article, we examine the asthma of President Theodore "TR" Roosevelt (1858-1919). Through a comprehensive review of thousands of source documents, and a modern understanding of asthma, we examine several misunderstandings, including the longstanding assertion that TR's illness was "psychosomatic." TR's respiratory problems began in early childhood, and the historical record provides strong evidence for poorly controlled, persistent asthma. Like many patients, his asthma entered a relatively quiescent stage during adolescence, coincident with initiation of a vigorous exercise program when TR was 12 years old. Nevertheless, TR continued to suffer serious asthma exacerbations, both in adolescence and adulthood. Although psychosocial issues affect most chronic diseases, there is little (if any) support for assertions that TR's asthma was psychosomatic. We believe that TR's childhood struggles with asthma, and the misconception that he vanquished his illness through exercise, were experiences that profoundly affected his worldview. TR is known for his appreciation of life's struggles and for a bedrock belief that people can create major change with sufficient motivation and hard work. In different ways, misunderstandings about asthma contributed to the early development of these personal characteristics. Together with later experiences, they contributed to a lifetime of action that changed modern history. (C) 2015 American Academy of Allergy, Asthma & Immunology C1 [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. [Roosevelt, Tweed] Theodore Roosevelt Assoc, New York, NY USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, 125 Nashua St,Suite 920, Boston, MA 02114 USA. EM ccamargo@partners.org NR 26 TC 0 Z9 0 U1 1 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 SEP-OCT PY 2015 VL 3 IS 5 BP 696 EP + DI 10.1016/j.jaip.2015.06.010 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA DB6ZX UT WOS:000368665300009 PM 26271837 ER PT J AU Hasegawa, K Bittner, JC Nonas, SA Stoll, SJ Watase, T Gabriel, S Herrera, V Camargo, CA AF Hasegawa, Kohei Bittner, Jane C. Nonas, Stephanie A. Stoll, Samantha J. Watase, Taketo Gabriel, Susan Herrera, Vivian Camargo, Carlos A., Jr. TI Children and Adults With Frequent Hospitalizations for Asthma Exacerbation, 2012-2013: A Multicenter Observational Study SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE LA English DT Article DE Asthma; Hospitalization; Inhaled corticosteroids; Asthma specialist; Multicenter study ID CHILDHOOD ASTHMA; EMERGENCY-DEPARTMENT; UNITED-STATES; POPULATION; READMISSION; MANAGEMENT; MEDICATION; RATES; RISK; CARE AB BACKGROUND: Earlier studies reported that many patients were frequently hospitalized for asthma exacerbation. However, there have been no recent multicenter studies to characterize this patient population with high morbidity and health care utilization. OBJECTIVE: To examine the proportion and characteristics of children and adults with frequent hospitalizations for asthma exacerbation. METHODS: A multicenter chart review study of patients aged 2 to 54 years who were hospitalized for asthma exacerbation at 1 of 25 hospitals across 18 US states during the period 2012 to 2013 was carried out. The primary outcome was frequency of hospitalizations for asthma exacerbation in the past year (including the index hospitalization). RESULTS: The cohort included 369 children (aged 2-17 years) and 555 adults (aged 18-54 years) hospitalized for asthma exacerbation. Over the 12-month period, 36% of the children and 42% of the adults had 2 or more (frequent) hospitalizations for asthma exacerbation. Among patients with frequent hospitalizations, guideline-recommended outpatient management was suboptimal. For example, among adults, 32% were not on inhaled corticosteroids at the time of index hospitalization and 75% had no evidence of a previous evaluation by an asthma specialist. At hospital discharge, among adults with frequent hospitalizations who had used no controller medications previously, 37% were not prescribed inhaled corticosteroids. Likewise, during a 3-month post-discharge period, 64% of the adults with frequent hospitalizations were not referred to an asthma specialist. Although the proportion of patients who did not receive these guideline-recommended outpatient care appeared higher in adults, these preventive measures were still underutilized in children; for example, 38% of the children with frequent hospitalizations were not referred to asthma specialist after the index hospitalization. CONCLUSIONS: This multicenter study of US patients hospitalized with asthma exacerbation demonstrated a disturbingly high proportion of patients with frequent hospitalizations and ongoing evidence of suboptimal longitudinal asthma care. (C) 2015 American Academy of Allergy, Asthma & Immunology C1 [Hasegawa, Kohei; Bittner, Jane C.; Stoll, Samantha J.; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Nonas, Stephanie A.] Oregon Hlth & Sci Univ Hosp, Div Pulm & Crit Care Med, Portland, OR USA. [Watase, Taketo] Univ Washington, Harborview Med Ctr, Div Emergency Med, Seattle, WA 98104 USA. [Gabriel, Susan; Herrera, Vivian] Novartis Pharmaceut, E Hanover, NJ USA. RP Hasegawa, K (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 326 Cambridge St,Ste 410, Boston, MA 02114 USA. EM khasegawa1@partners.org FU Novartis Pharmaceuticals Corporation FX This study was supported by Novartis Pharmaceuticals Corporation (principal investigator C.A.C. Jr). The sponsor had no role in the conduct of the study, nor collection, management, or analysis of the data. NR 27 TC 3 Z9 3 U1 3 U2 6 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 SEP-OCT PY 2015 VL 3 IS 5 BP 751 EP + DI 10.1016/j.jaip.2015.05.003 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA DB6ZX UT WOS:000368665300017 PM 26028297 ER PT J AU Iammatteo, M Blumenthal, KG Saff, R Long, AA Banerji, A AF Iammatteo, Melissa Blumenthal, Kimberly G. Saff, Rebecca Long, Aidan A. Banerji, Aleena TI Safety of graded challenge in allergic patients SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE LA English DT Letter C1 [Iammatteo, Melissa] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. [Blumenthal, Kimberly G.; Saff, Rebecca; Long, Aidan A.; Banerji, Aleena] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. RP Iammatteo, M (reprint author), Massachusetts Gen Hosp, Dept Med, Gray Bigelow 740,55 Fruit St, Boston, MA 02114 USA. EM miammatteo@partners.org FU NHLBI NIH HHS [T32HL116275] NR 3 TC 0 Z9 0 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 SEP-OCT PY 2015 VL 3 IS 5 BP 826 EP 827 DI 10.1016/j.jaip.2015.05.014 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA DB6ZX UT WOS:000368665300041 PM 26099817 ER PT J AU Davids, M Kim, HT Gilbert, E Cowen, L Francoeur, K Hellman, JM Arnason, JE Fisher, DC Brown, JR AF Davids, Matthew Kim, Haesook T. Gilbert, Elizabeth Cowen, Leslie Francoeur, Karen Hellman, Jeffrey M. Arnason, Jon E. Fisher, David C. Brown, Jennifer R. TI Preliminary results of a phase Ib study of duvelisib in combination with FCR (dFCR) in previously untreated, younger patients with CLL SO LEUKEMIA & LYMPHOMA LA English DT Meeting Abstract C1 [Davids, Matthew; Kim, Haesook T.; Gilbert, Elizabeth; Cowen, Leslie; Francoeur, Karen; Hellman, Jeffrey M.; Fisher, David C.; Brown, Jennifer R.] Harvard Univ, Dana Farber Canc Inst, Boston, MA USA. [Arnason, Jon E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD SEP 1 PY 2015 VL 56 SU 1 SI SI MA 25 BP 19 EP 19 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA DB7QH UT WOS:000368710200026 ER PT J AU Ma, S Roberts, AW Brander, D Kipps, TJ Barrientos, JC Davids, MS Anderson, MA Choi, M Tam, C Magee, L Kreutzer, J Kim, J Dimovski, B Mason-Bright, T Prine, B Zhu, M Humerickhouse, RA Seymour, JF AF Ma, Shuo Roberts, Andrew W. Brander, Danielle Kipps, Thomas J. Barrientos, Jacqueline C. Davids, Matthew S. Anderson, Mary Ann Choi, Michael Tam, Constantine Magee, Lisa Kreutzer, Jennifer Kim, Jennifer Dimovski, Belinda Mason-Bright, Tanita Prine, Betty Zhu, Ming Humerickhouse, Rod A. Seymour, John F. TI Venetoclax (ABT-199/GDC-0199) combined with rituximab induces deep responses in patients with relapsed/refractory chronic lymphocytic leukemia SO LEUKEMIA & LYMPHOMA LA English DT Meeting Abstract C1 [Ma, Shuo; Kreutzer, Jennifer] Northwestern Univ, Chicago, IL 60611 USA. [Roberts, Andrew W.; Anderson, Mary Ann; Magee, Lisa] Royal Melbourne Hosp, Melbourne, Vic, Australia. [Roberts, Andrew W.; Anderson, Mary Ann; Magee, Lisa] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia. [Brander, Danielle] Duke Univ, Med Ctr, Durham, NC USA. [Kipps, Thomas J.; Choi, Michael; Kim, Jennifer] Univ Calif San Diego, San Diego, CA 92103 USA. [Barrientos, Jacqueline C.] Hofstra North Shore LIJ Sch Med, Hempstead, NY USA. [Davids, Matthew S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tam, Constantine; Dimovski, Belinda; Seymour, John F.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Mason-Bright, Tanita; Prine, Betty; Zhu, Ming; Humerickhouse, Rod A.] AbbVie, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD SEP 1 PY 2015 VL 56 SU 1 SI SI MA 28 BP 21 EP 21 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA DB7QH UT WOS:000368710200029 ER PT J AU Kasar, S Kim, J Improgo, R Tiao, G Polak, P Lawrence, MS Fernandes, SM Hoang, K Kim, HT Getz, G Brown, JR AF Kasar, Siddha Kim, Jaegil Improgo, Reina Tiao, Grace Polak, Paz Lawrence, Michael S. Fernandes, Stacey M. Hoang, Kevin Kim, Haesook T. Getz, Gad Brown, Jennifer R. TI Two distinct activation-induced cytidine deaminase (AID) signatures identified in the evolution of indolent chronic lymphocytic leukemia using whole genome sequencing SO LEUKEMIA & LYMPHOMA LA English DT Meeting Abstract C1 [Kasar, Siddha; Improgo, Reina; Fernandes, Stacey M.; Hoang, Kevin; Kim, Haesook T.; Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tiao, Grace; Polak, Paz; Lawrence, Michael S.; Getz, Gad] Broad Inst MIT & Harvard, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD SEP 1 PY 2015 VL 56 SU 1 SI SI MA 83 BP 64 EP 65 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA DB7QH UT WOS:000368710200084 ER PT J AU Pavlasova, G Borsky, M Seda, V Cerna, K Osickova, J Mayer, J Pospisilova, S Davids, M Brown, J Mraz, M AF Pavlasova, Gabriela Borsky, Marek Seda, Vaclav Cerna, Katerina Osickova, Jitka Mayer, Jiri Pospisilova, Sarka Davids, Matthew Brown, Jennifer Mraz, Marek TI Microenvironmental interactions up-regulate CD20 expression in CLL B cells, but confer resistance to rituximab SO LEUKEMIA & LYMPHOMA LA English DT Meeting Abstract C1 [Pavlasova, Gabriela; Seda, Vaclav; Cerna, Katerina; Pospisilova, Sarka; Mraz, Marek] CEITEC MU, Mol Med, Brno, Czech Republic. [Borsky, Marek; Osickova, Jitka; Mayer, Jiri] Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic. [Davids, Matthew; Brown, Jennifer] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RI Mraz, Marek/E-1774-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD SEP 1 PY 2015 VL 56 SU 1 SI SI MA 94 BP 76 EP 77 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA DB7QH UT WOS:000368710200095 ER PT J AU Deng, J Isik, E Fernandes, S Brown, JR Letai, A Davids, M AF Deng, Jing Isik, Elif Fernandes, Stacey Brown, Jennifer R. Letai, Anthony Davids, Matthew TI Ibrutinib therapy increases BCL2 dependence and enhances sensitivity to venetoclax in CLL patients SO LEUKEMIA & LYMPHOMA LA English DT Meeting Abstract C1 [Deng, Jing; Isik, Elif; Fernandes, Stacey; Brown, Jennifer R.; Letai, Anthony; Davids, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD SEP 1 PY 2015 VL 56 SU 1 SI SI MA 116 BP 96 EP 97 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA DB7QH UT WOS:000368710200117 ER PT J AU Paiva, C Brown, J Danilov, A AF Paiva, Cody Brown, Jennifer Danilov, Alexey TI Cdk inhibitor P1446a induces apoptosis in a C-jun N-terminal kinase (Jnk)-dependent manner in chronic lymphocytic leukemia (CLL) B-cells SO LEUKEMIA & LYMPHOMA LA English DT Meeting Abstract C1 [Paiva, Cody; Danilov, Alexey] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Brown, Jennifer] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD SEP 1 PY 2015 VL 56 SU 1 SI SI MA 115 BP 96 EP 96 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA DB7QH UT WOS:000368710200116 ER PT J AU Yu, LJ Kim, H Kasar, S Benien, P Du, W Hoang, K Improgo, R Fernandes, S Klitgaard, JL Lee, C Getz, G Setlur, SR Brown, J AF Yu, Lijian Kim, Haesook Kasar, Siddha Benien, Parul Du, Wei Hoang, Kevin Improgo, Reina Fernandes, Stacey Klitgaard, Josephine L. Lee, Charles Getz, Gad Setlur, Sunita R. Brown, Jennifer TI Increasing copy number abnormalities and somatic mutations including TP53 worsen overall survival in 17p deleted CLL SO LEUKEMIA & LYMPHOMA LA English DT Meeting Abstract C1 [Yu, Lijian; Kim, Haesook; Kasar, Siddha; Hoang, Kevin; Improgo, Reina; Fernandes, Stacey; Klitgaard, Josephine L.; Brown, Jennifer] Dana Farber Canc Inst, Boston, MA 02115 USA. [Benien, Parul; Du, Wei; Lee, Charles] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD SEP 1 PY 2015 VL 56 SU 1 SI SI MA 146 BP 122 EP 122 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA DB7QH UT WOS:000368710200147 ER PT J AU Kutsch, N Bahlo, J Bergmann, M Byrd, J Doehner, H Eichhorst, B Else, M Geisler, C Grever, M Lepretre, S Neuberg, D Oscier, D Rosenquist, R Robak, T Shanafelt, T Stilgenbauer, S Hallek, M AF Kutsch, Nadine Bahlo, Jasmin Bergmann, Manuela Byrd, John Doehner, Hartmut Eichhorst, Barbara Else, Monica Geisler, Christian Grever, Michael Lepretre, Stephane Neuberg, Donna Oscier, David Rosenquist, Richard Robak, Tadeusz Shanafelt, Tait Stilgenbauer, Stephan Hallek, Michael CA CLL-IPI Working Grp TI The international prognostic index for patients with CLL(CLL-IPI) - an international meta-analysis SO LEUKEMIA & LYMPHOMA LA English DT Meeting Abstract C1 [Kutsch, Nadine; Bahlo, Jasmin; Eichhorst, Barbara] Univ Hosp Cologne, Dept Internal Med 1, Cologne, Germany. [Kutsch, Nadine; Bahlo, Jasmin; Eichhorst, Barbara] Univ Hosp Cologne, Ctr Integrated Oncol Cologne Bonn, Cologne, Germany. [Bergmann, Manuela] Klinikum Schwabing, Dept Hematol Oncol Immunol Palliat Care & Infect, Munich, Germany. [Byrd, John; Grever, Michael] Ohio State Univ, Dept Hematol, Columbus, OH 43210 USA. [Doehner, Hartmut] Univ Hosp Ulm, Dept Internal Med 3, Ulm, Germany. [Else, Monica] Inst Canc Res, Div Mol Pathol, London SW3 6JB, England. [Geisler, Christian] Rigshosp, Dept Hematol, DK-2100 Copenhagen, Denmark. [Lepretre, Stephane] Ctr Henri Becquerel, Dept Hematol, F-76038 Rouen, France. [Neuberg, Donna] Dana Farber Canc Inst, Biostat & Computat Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD SEP 1 PY 2015 VL 56 SU 1 SI SI MA 151 BP 127 EP 127 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA DB7QH UT WOS:000368710200152 ER PT J AU Montillo, M O'Brien, S Tedeschi, A Byrd, J Dearden, C Gill, D Brown, J Barrientos, J Mulligan, S Furman, R Cymbalista, F Plascencia, C Chang, S Hsu, E James, D Hillmen, P AF Montillo, Marco O'Brien, Susan Tedeschi, Alessandra Byrd, John Dearden, Claire Gill, Devinder Brown, Jennifer Barrientos, Jacqueline Mulligan, Stephen Furman, Richard Cymbalista, Florence Plascencia, Clara Chang, Stephen Hsu, Emily James, Danelle Hillmen, Peter TI Ibrutinib in patients with autoimmune cytopenias and previously treated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) from the phase 3 RESONATETM study SO LEUKEMIA & LYMPHOMA LA English DT Meeting Abstract C1 Osped Niguarda Ca Granda, Milan, Italy. Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX USA. Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. Royal Marsden Hosp, London SW3 6JJ, England. Princess Alexandra Hosp, Dept Haematol, Woolloongabba, Qld 4102, Australia. Dana Farber Canc Inst, Boston, MA 02115 USA. Shore LIJ Canc Inst, New York, NY USA. Royal N Shore Hosp, Sydney Med Sch, Sydney, NSW, Australia. New York Presbyterian Hosp, Cornell Med College, New York, NY USA. Avicenne, Paris, France. LLC, Dallas, TX USA. Leeds Teaching Hosp, St James Inst Oncol, Leeds, W Yorkshire, England. NR 0 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD SEP 1 PY 2015 VL 56 SU 1 SI SI MA 179 BP 150 EP 151 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA DB7QH UT WOS:000368710200180 ER PT J AU Pagel, J Brown, J Hillmen, P O'Brien, S Barrientos, J Reddy, N Coutre, S Tam, C Mulligan, S Jaeger, U Barr, P Furman, R Kipps, T Cymbalista, F Thornton, P Caligaris-Cappio, F Delgado, J Montillo, M Devos, S Moreno, C Munir, T Burger, J Chung, D Lin, J Gau, L Chang, B Cole, G Hsu, E James, D Byrd, J AF Pagel, John Brown, Jennifer Hillmen, Peter O'Brien, Susan Barrientos, Jacqueline Reddy, Nishitha Coutre, Steven Tam, Constantine Mulligan, Stephen Jaeger, Ulrich Barr, Paul Furman, Richard Kipps, Thomas Cymbalista, Florence Thornton, Patrick Caligaris-Cappio, Federico Delgado, Julio Montillo, Marco DeVos, Sven Moreno, Carol Munir, Talha Burger, Jan Chung, Devon Lin, Jennifer Gau, Linda Chang, Betty Cole, George Hsu, Emily James, Danelle Byrd, John TI Updated efficacy including genetic subgroup analysis and overall safety in the phase 3 RESONATE trial of ibrutinib versus ofatumumab in previously-treated CLL/SLL SO LEUKEMIA & LYMPHOMA LA English DT Meeting Abstract C1 Swedish Canc Inst, Seattle, WA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Leeds Teaching Hosp, St James Inst Oncol, Leeds, W Yorkshire, England. Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX USA. North Shore Long Isl Jewish Hlth Syst, Manhasset, NY USA. Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN 37235 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. St Vincents Hosp, Melbourne, Vic, Australia. Royal N Shore Hosp, Sydney Med Sch, Sydney, NSW, Australia. Med Univ Vienna, Vienna, Austria. Univ Rochester, Ctr Canc, Rochester, NY USA. Weill Cornell Med Coll, New York, NY USA. Univ Calif San Diego, Moores UCSD Canc Ctr, San Diego, CA 92103 USA. Hop Avicenne, Paris, France. Beaumont Hosp, Dublin 9, Ireland. Univ Vita Salute San Raffaele, Milan, Italy. Hosp Clin Barcelona, Barcelona, Spain. Osped Niguarda Ca Granda, Milan, Italy. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. Hosp La Santa Creu St Pau, Barcelona, Spain. Pharmacyclics LLC, Sunnyvale, CA USA. Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. NR 0 TC 1 Z9 1 U1 1 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD SEP 1 PY 2015 VL 56 SU 1 SI SI MA 181 BP 153 EP 154 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA DB7QH UT WOS:000368710200182 ER PT J AU Ott, HC AF Ott, Harald C. TI Perfusion Decellularization of Discarded Human Kidneys: A Valuable Platform for Organ Regeneration SO TRANSPLANTATION LA English DT Editorial Material ID CELLS C1 [Ott, Harald C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Thorac Surg, Boston, MA 02114 USA. RP Ott, HC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Organ Engn & Regenerat, 185 Cambridge St,CPZN 4812, Boston, MA 02114 USA. EM hott@partners.org FU NIH HHS [DP2 OD008749] NR 11 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD SEP PY 2015 VL 99 IS 9 BP 1753 EP 1753 DI 10.1097/TP.0000000000000810 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DC2YV UT WOS:000369086000019 PM 26203856 ER PT J AU Reese, SR Wilson, NA Huang, GW Redfield, RR Zhong, WX Djamali, A AF Reese, Shannon R. Wilson, Nancy A. Huang, Gengwen Redfield, Robert R., III Zhong, Weixiong Djamali, Arjang TI Calcineurin Inhibitor Minimization With Ixazomib, an Investigational Proteasome Inhibitor, for the Prevention of Antibody Mediated Rejection in a Preclinical Model SO TRANSPLANTATION LA English DT Article ID RELAPSED/REFRACTORY MULTIPLE-MYELOMA; CHRONIC ALLOGRAFT NEPHROPATHY; DONOR-SPECIFIC ANTIBODIES; KIDNEY-TRANSPLANTATION; PLASMA-CELLS; RENAL-TRANSPLANTATION; BORTEZOMIB; BAFF; DIAGNOSIS; RAT AB Background. There is a need for new immunosuppression strategies to minimize calcineurin inhibitor (CNI) toxicity while effectively preventing antibody-mediated rejection (AMR). Methods. We tested the efficacy of an investigational proteasome inhibitor, ixazomib, alone and in a CNI minimization strategy in a rat kidney transplant model of transfusion-elicited acute AMR. Nonsensitized (naive) and sensitized allograft recipients were randomized into 4 treatment groups (8 groups total, n = 3 to 6 in each group) and treated for 1 week. Groups included: no treatment, full dose cyclosporine (CsA, 10 mg/kg per day), ixazomib (0.25 mg/kg on days -5, -2 and +2) alone, and half dose CsA (5 mg/kg per day) + ixazomib. Results. Compared to untreated animals, ixazomib alone or in combination with 1/2 dose CsA reduced donor-specific antibody, intragraft transcripts for chemokines CCL-21 and CXCL-13, and CD19 expression in both sensitized and naive transplants. Compared to full dose CsA, the CNI minimization strategy with ixazomib inhibited AMR and allograft injury as evidenced by reduced C4d staining in peritubular capillaries, microcirculation inflammation, splenic plasma cells, circulating B cell activating factor, and intragraft transcripts for major histocompatibility complex class II, Toll-like receptors (TLR-1, TLR-10, and TLR-12) and CCL-21 and CXCL-13 in sensitized animals, indicating downregulation of B cell activation, antigen presentation and T-cell and B-cell signaling. Conclusions. These studies suggest that CNI minimization strategies including ixazomib are effective to prevent AMR including in sensitized kidney allograft recipients. Clinical studies are needed to determine the role of novel proteasome inhibitors for the prevention and treatment of AMR. C1 [Reese, Shannon R.; Wilson, Nancy A.; Djamali, Arjang] Univ Wisconsin, Dept Med, Div Nephrol, Sch Med & Publ Hlth, Madison, WI USA. [Huang, Gengwen; Redfield, Robert R., III; Djamali, Arjang] Univ Wisconsin, Dept Surg, Div Transplantat, Sch Med & Publ Hlth, Madison, WI USA. [Zhong, Weixiong] Univ Wisconsin, Dept Pathol & Lab Med, Sch Med & Publ Hlth, Madison, WI USA. [Zhong, Weixiong] William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Serv, Madison, WI USA. RP Djamali, A (reprint author), UWSMPH, 5142 MFCB,1685 Highland Ave, Madison, WI 53705 USA. EM axd@medicine.wisc.edu NR 37 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD SEP PY 2015 VL 99 IS 9 BP 1785 EP 1795 DI 10.1097/TP.0000000000000736 PG 11 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DC2YV UT WOS:000369086000024 PM 25919767 ER PT J AU Kheirkhah, A Muller, R Mikolajczak, J Ren, A Kadas, EM Zimmermann, H Pruess, H Paul, F Brandt, AU Hamrah, P AF Kheirkhah, Ahmad Muller, Rodrigo Mikolajczak, Janine Ren, Ai Kadas, Ella Maria Zimmermann, Hanna Pruess, Harald Paul, Friedemann Brandt, Alexander U. Hamrah, Pedram TI Comparison of Standard Versus Wide-Field Composite Images of the Corneal Subbasal Layer by In Vivo Confocal Microscopy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE in vivo confocal microscopy; corneal nerves; wide-field composite images ID HERPES-ZOSTER OPHTHALMICUS; LASER-SCANNING MICROSCOPY; NERVE PLEXUS; DIABETIC-NEUROPATHY; CELL-DENSITY; EPITHELIUM; MORPHOLOGY; KERATITIS; SENSITIVITY; MARKERS AB PURPOSE. To evaluate whether the densities of corneal subbasal nerves and epithelial immune dendritiform cells (DCs) are comparable between a set of three representative standard images of in vivo confocal microscopy (IVCM) and the wide-field mapped composite IVCM images. METHODS. This prospective, cross-sectional, and masked study included 110 eyes of 58 patients seen in a neurology clinic who underwent laser-scanning IVCM (Heidelberg Retina Tomograph 3) of the central cornea. Densities of subbasal corneal nerves and DCs were compared between the average of three representative standard images and the wide-field mapped composite images, which were reconstructed by automated mapping. RESULTS. There were no statistically significant differences between the average of three representative standard images (0.16 mm(2) each) and the wide-field composite images (1.29 +/- 0.64 mm(2)) in terms of mean subbasal nerve density (17.10 +/- 6.10 vs. 17.17 +/- 5.60 mm/mm(2), respectively, P = 0.87) and mean subbasal DC density (53.2 +/- 67.8 vs. 49.0 +/- 54.3 cells/mm(2), respectively, P = 0.43). However, there were notable differences in subbasal nerve and DC densities between these two methods in eyes with very low nerve density or very high DC density. CONCLUSIONS. There are no significant differences in the mean subbasal nerve and DC densities between the average values of three representative standard IVCM images and wide-field mapped composite images. Therefore, these standard images can be used in clinical studies to accurately measure cellular structures in the subbasal layer. C1 [Kheirkhah, Ahmad; Muller, Rodrigo; Ren, Ai; Hamrah, Pedram] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med,Dept Ophthalmol, Ocular Surface Imaging Ctr,Cornea & Refract Surg, Boston, MA 02114 USA. [Muller, Rodrigo; Hamrah, Pedram] Univ Fed Sao Paulo, Paulista Sch Med, Dept Ophthalmol & Visual Sci, Sao Paulo, Brazil. [Mikolajczak, Janine; Kadas, Ella Maria; Zimmermann, Hanna; Paul, Friedemann; Brandt, Alexander U.] Charite, NeuroCure Clin Res Ctr, D-13353 Berlin, Germany. [Pruess, Harald] German Ctr Neurodegenerat Dis DZNE, Berlin, Germany. [Pruess, Harald; Paul, Friedemann] Charite, Dept Neurol, D-13353 Berlin, Germany. RP Hamrah, P (reprint author), Tufts Univ, Tufts Med Ctr, Boston Image Reading Ctr, Cornea Serv,New England Eye Ctr,Sch Med, 800 Washington St, Boston, MA 02111 USA. EM phamrah@tuftsmedicalcenter.org FU German Research Foundation [DFG Exc. 257]; NIH [R01-EY022695]; Falk Medical Research Foundation; Massachusetts Eye and Ear Infirmary Foundation; Career Development Award from Research to Prevent Blindness FX Supported by German Research Foundation (DFG Exc. 257) (AUB), NIH R01-EY022695 (PH), Falk Medical Research Foundation (PH), Massachusetts Eye and Ear Infirmary Foundation (PH), and a Career Development Award from Research to Prevent Blindness (PH). The authors alone are responsible for the content and writing of the paper. NR 43 TC 5 Z9 5 U1 0 U2 3 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 SEP PY 2015 VL 56 IS 10 BP 5801 EP 5807 DI 10.1167/iovs.15-17434 PG 7 WC Ophthalmology SC Ophthalmology GA DB3QL UT WOS:000368426300013 PM 26325419 ER PT J AU Schlereth, SL Iden, S Mescher, M Ksander, BR Bosch, JJ Cursiefen, C Heindl, LM AF Schlereth, Simona L. Iden, Sandra Mescher, Melina Ksander, Bruce R. Bosch, Jacobus J. Cursiefen, Claus Heindl, Ludwig M. TI A Novel Model of Metastatic Conjunctival Melanoma in Immune-Competent Mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE conjunctival melanoma; mouse model; (lymph)-angiogenesis; ocular melanoma; B16F10; hepatocyte growth factor; metastasis ID TUMOR-ASSOCIATED LYMPHANGIOGENESIS; CILIARY-BODY-MELANOMAS; UVEAL MELANOMA; EXTRAOCULAR-EXTENSION; ORTHOTOPIC TRANSPLANTATION; PROGNOSTIC-SIGNIFICANCE; MALIGNANT MELANOMAS; UNITED-STATES; MOUSE MODEL; NUDE-MOUSE AB PURPOSE. Conjunctival melanoma (CM) is an ocular surface tumor that can lead to fatal metastases. Patients developing, tumor-associated lymphangiogenesis have a significantly increased risk of metastatic disease, because tumor spread primarily occurs via lymphatic vessels to the draining lymph node. Here, we describe a novel immune-competent mouse model of CM that displays tumor-associated lymphangiogenesis with development of metastatic tumors. METHODS. C57BL/6N mice received C57BL/6N-derived dermalmelanoma cells (hepatocyte growth factor [HGF] cyclin dependent kinase-4 [Cdk4]+) or B16F10 via subconjunctival injection. A clinical score quantified primary tumor growth and metastases were identified by macroscopic examination of the draining lymph nodes, lung, and spleen. Confirmation of tumors and metastases was achieved by immunohistochemical staining for markers of pigmented cells (tyrosinase related protein-2 [TRP2]) and S-100, and of cell proliferation (Ki67). The intra- and peritumoral CD31+ blood and lymphatic vessel endothelium hyaluronan receptor-1 (LYVE-1)+ lymphatic vessels were quantified immunohistochemically. RESULTS. All mice rapidly developed aggressive TRP2+, S100+, and Ki67+ CM. Metastatic tumors were found in the lymph node (9%) and lung (6%) of HGF-Cdk4(R24C)-treatedmice and in the spleen (8%) and lung (17%) of B16F10-treated mice. The amount of peri- and intratumoral blood vessels was significantly increased compared with lymphatic vessels. CONCLUSIONS. This CM model in immune-competent animals offers new possibilities to study the pathobiology of tumor growth, invasion, and mechanisms of metastatic tumor spread, and provides a robust model to explore new immune-based and antilymphangiogenic treatment modalities of this malignancy. C1 [Schlereth, Simona L.; Cursiefen, Claus; Heindl, Ludwig M.] Univ Cologne, Dept Ophthalmol, D-50924 Cologne, Germany. [Iden, Sandra; Mescher, Melina] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50924 Cologne, Germany. [Iden, Sandra; Mescher, Melina] Univ Cologne, Ctr Mol Med Cologne, D-50924 Cologne, Germany. [Ksander, Bruce R.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA 02114 USA. [Ksander, Bruce R.] Harvard Univ, Sch Med, Boston, MA USA. [Bosch, Jacobus J.] Univ Erlangen Nurnberg, Dept Internal Med Hematol & Oncol 5, D-91054 Erlangen, Germany. RP Schlereth, SL (reprint author), Univ Cologne, Dept Ophthalmol, Kerpenerstr 62, D-50924 Cologne, Germany. EM Simona.schlereth@uk-koeln.de FU German Research Foundation [FOR 2240, HE 6743/2-1, HE 6743/3-1, BO 4000/2-1, BO 4000/3-1, CU 47/6-1]; Excellence Initiative by the German federal and state governments (CECAD Cologne); DFG [ID79/1-1, ID79/1-2, CRC829/A10]; Stiftung Kolner Krebsforschung (Exzellenz Initiieren); CMMC project [A3]; German Cancer Aid [SFB 829, 79/1-1]; GEROK Program University of Cologne; EU COST BM1302 "Joining Forces in Corneal Regeneration'' FX Supported by German Research Foundation (FOR 2240 "[Lymph] Angiogenesis and Cellular Immunity in Inflammatory Diseases of the Eye'' [JJB, CC, LMH]; HE 6743/2-1 and HE 6743/3-1 [LMH]; BO 4000/2-1 and BO 4000/3-1 [JJB]; CU 47/6-1 [CC]); the Excellence Initiative by the German federal and state governments (CECAD Cologne) (SI); DFG Grants ID79/1-1, ID79/1-2, and CRC829/A10 (SI); the Stiftung Kolner Krebsforschung (Exzellenz Initiieren) (SI); CMMC project grant A3 (SI); SFB 829 ID 79/1-1 (SI), German Cancer Aid (LMH, CC), GEROK Program University of Cologne (SLS, LMH), and EU COST BM1302 "Joining Forces in Corneal Regeneration'' (CC). The authors alone are responsible for the content and writing of the paper. NR 45 TC 1 Z9 1 U1 2 U2 3 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 SEP PY 2015 VL 56 IS 10 BP 5965 EP 5973 DI 10.1167/iovs.15-17290 PG 9 WC Ophthalmology SC Ophthalmology GA DB3QL UT WOS:000368426300035 PM 26377082 ER PT J AU Verhulst, S Bharadwaj, HM Mehraei, G Shera, CA Shinn-Cunningham, BG AF Verhulst, Sarah Bharadwaj, Hari M. Mehraei, Golbarg Shera, Christopher A. Shinn-Cunningham, Barbara G. TI Functional modeling of the human auditory brainstem response to broadband stimulation SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID INNER-HAIR CELL; AMPLITUDE-MODULATED TONES; INDUCED COCHLEAR NEUROPATHY; BASILAR-MEMBRANE RESPONSES; GUINEA-PIG COCHLEA; OTOACOUSTIC EMISSIONS; NERVE FIBERS; HEARING-LOSS; PHENOMENOLOGICAL MODEL; LOW-FREQUENCY AB Population responses such as the auditory brainstem response (ABR) are commonly used for hearing screening, but the relationship between single-unit physiology and scalp-recorded population responses are not well understood. Computational models that integrate physiologically realistic models of single-unit auditory-nerve (AN), cochlear nucleus (CN) and inferior colliculus (IC) cells with models of broadband peripheral excitation can be used to simulate ABRs and thereby link detailed knowledge of animal physiology to human applications. Existing functional ABR models fail to capture the empirically observed 1.2-2 ms ABR wave-V latency-vs-intensity decrease that is thought to arise from level-dependent changes in cochlear excitation and firing synchrony across different tonotopic sections. This paper proposes an approach where level-dependent cochlear excitation patterns, which reflect human cochlear filter tuning parameters, drive AN fibers to yield realistic level-dependent properties of the ABR wave-V. The number of free model parameters is minimal, producing a model in which various sources of hearing-impairment can easily be simulated on an individualized and frequency-dependent basis. The model fits latency-vs-intensity functions observed in human ABRs and otoacoustic emissions while maintaining rate-level and threshold characteristics of single-unit AN fibers. The simulations help to reveal which tonotopic regions dominate ABR waveform peaks at different stimulus intensities. (C) 2015 Acoustical Society of America. C1 [Verhulst, Sarah] Carl von Ossietzky Univ Oldenburg, Dept Med Phys & Acoust, Cluster Excellence Hearing4all & Med Phys, Carl Von Ossietzky Str 9-11, D-26129 Oldenburg, Germany. [Bharadwaj, Hari M.] Boston Univ, Ctr Computat Neurosci & Neural Technol, Boston, MA 02215 USA. [Bharadwaj, Hari M.; Mehraei, Golbarg; Shinn-Cunningham, Barbara G.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Shera, Christopher A.] Eaton Peabody Lab, Boston, MA 02114 USA. [Shinn-Cunningham, Barbara G.] Boston Univ, Ctr Computat Neurosci & Neural Technol, Boston, MA 02215 USA. [Bharadwaj, Hari M.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Mehraei, Golbarg] Harvard Univ, Program Speech & Hearing Biosci & Technol, Cambridge, MA 02139 USA. [Mehraei, Golbarg] MIT, Cambridge, MA 02139 USA. [Shera, Christopher A.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Verhulst, S (reprint author), Carl von Ossietzky Univ Oldenburg, Dept Med Phys & Acoust, Cluster Excellence Hearing4all & Med Phys, Carl Von Ossietzky Str 9-11, D-26129 Oldenburg, Germany. EM sarah.verhulst@uni-oldenburg.de FU Office of Assistant Secretary of Defense for Research and Engineering; DFG Cluster of Excellence [EXC 1077/1]; National Institute on Deafness and Other Communication Disorders [T32 DC00038]; [R01 DC003687] FX The authors thank Philip Joris, Mike Heinz, Laurel Carney, Ian Bruce, Muhammad Zilany, Filip Ronne, James Harte, Andrew Oxenham, Stephen Neely, Alessandro Altoe, Enrique Lopez-Poveda, and two anonymous reviewers for discussions related to the development and presentation of the model. This work was supported by R01 DC003687 (C.A.S.), a fellowship from the Office of Assistant Secretary of Defense for Research and Engineering (B.G.S.C.), DFG Cluster of Excellence EXC 1077/1 "Hearing4all" (S.V.), and Grant Number T32 DC00038 from the National Institute on Deafness and Other Communication Disorders (G.M.). NR 97 TC 6 Z9 6 U1 1 U2 5 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD SEP PY 2015 VL 138 IS 3 BP 1637 EP 1659 DI 10.1121/1.4928305 PG 23 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA DB6RX UT WOS:000368643800068 PM 26428802 ER PT J AU Bowen, ME Rowe, MA Hart-Hughes, S Barnett, S Ji, M AF Bowen, Mary Elizabeth Rowe, Meredeth A. Hart-Hughes, Stephanie Barnett, Scott Ji, Ming TI Characteristics of and Barriers to Functional Status Assessment in Assisted Living SO RESEARCH IN GERONTOLOGICAL NURSING LA English DT Article ID CLINICALLY IMPORTANT DIFFERENCE; PHYSICAL PERFORMANCE; BARTHEL INDEX; NURSING-HOMES; FACILITIES; STROKE; IMPAIRMENT; INSTRUMENT; RESIDENTS; ADMISSION AB The most commonly used functional status (FS) instruments were examined to determine the validity, reliability, sensitivity, and specifi city to change and feasibility in residents in an assisted living facility (ALF). Twenty-six ALF residents were assessed weekly for up to 8 months using six instruments. Group and single-subject analyses were used to examine associations between instruments and acute events. Two were problematic initially (Katz Index of Independence in Activities of Daily Living and hand grip) and were excluded early in the study. Of the remaining instruments, only the Barthel Index and Resident Assessment Instrument had acceptable psychometric profi les. However, these instruments were either not feasible in this environment or did not capture the full range of FS in this population. The current study's fi ndings suggest that instruments commonly used to measure FS may be inadequate for this population and environment. These fi ndings may be used to develop assessment methods for ALF residents that capture both the full range of FS in ALF settings as well as acute and long-term changes in functioning. C1 [Bowen, Mary Elizabeth] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Bowen, Mary Elizabeth] West Chester Univ Penn, Dept Hlth, W Chester, PA 19383 USA. [Bowen, Mary Elizabeth] West Chester Univ Penn, Gerontol Certificate Hlth Aging, W Chester, PA USA. [Rowe, Meredeth A.; Ji, Ming] Univ S Florida, Coll Nursing, Tampa, FL USA. [Hart-Hughes, Stephanie] James A Haley Vet Hosp, Patient Safety Ctr Inquiry, Tampa, FL 33612 USA. [Barnett, Scott] Amer Nurses Credentialing Ctr, Res, Silver Spring, MD USA. RP Bowen, ME (reprint author), West Chester Univ Penn, Sturzebecker Hlth Sci Ctr 315, Dept Hlth, W Chester, PA 19383 USA.; Bowen, ME (reprint author), West Chester Univ Penn, Sturzebecker Hlth Sci Ctr 315, Gerontol Certificate Hlth Aging, W Chester, PA 19383 USA. EM mbowen@wcupa.edu FU Rehabilitation Research and Development Career Award at the Department of Veterans Affairs (VA) [E7503W] FX The authors have disclosed no potential conflicts of interest, financial or otherwise. This work was supported by a Rehabilitation Research and Development Career Award at the Department of Veterans Affairs (VA; E7503W). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the VA or the United States government. The authors acknowledge Dr. Susan C. McMillan for her helpful comments and suggestions in the early stages of this study, Mr. Robert Byrd for his help with data management, Ms. Lisa Goff and Ms. Raquel Elliot for data collection, and Dr. Mary Ersek for her editorial comments. The authors also acknowledge the University of Pennsylvania, School of Nursing and the anonymous reviewers of Research in Gerontological Nursing for their valuable comments and suggestions that helped improve the manuscript. NR 33 TC 1 Z9 1 U1 2 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1940-4921 EI 1938-2464 J9 RES GERONTOL NURS JI Res. Gerontol. Nurs. PD SEP-OCT PY 2015 VL 8 IS 5 BP 220 EP 230 DI 10.3928/19404921-20150406-01 PG 11 WC Nursing SC Nursing GA DB7AK UT WOS:000368666600003 PM 25893725 ER PT J AU Perkins, SH Stensland, KD Galsky, MD Sivendran, S AF Perkins, Sara Harcharik Stensland, Kristian D. Galsky, Matthew D. Sivendran, Shanthi TI An Analysis of the Clinical Trial Landscape for Cutaneous Melanoma SO CUTIS LA English DT Article ID UNTREATED MELANOMA; FOLLOW-UP; VEMURAFENIB; IPILIMUMAB; MANAGEMENT; CANCER; DABRAFENIB; TRAMETINIB; NIVOLUMAB; MUTATION AB Recognizing current trends and obstacles in melanoma clinical trial development is critical to future progress in this field. This article examines the melanoma research enterprise to identify changing trends and potential barriers to success. All trials registered at ClinicalTrials. gov after September 2005 were evaluated for possible inclusion. A total of 777 interventional trials designed specifically for cutaneous melanoma patients were included. Geographic trial distribution as well as disease state and type of intervention were analyzed and compared among each group. ClinicalTrials. gov is an invaluable tool to study the research enterprise. Further studies are needed on prevention and early detection of melanoma in the curative setting, a critical role for dermatologists. C1 [Perkins, Sara Harcharik] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Stensland, Kristian D.] Lahey Hosp & Med Ctr, Dept Surg, Burlington, MA USA. [Stensland, Kristian D.] Lahey Hosp & Med Ctr, Dept Urol, Burlington, MA USA. [Galsky, Matthew D.] Icahn Sch Med Mt Sinai, Tisch Canc Inst, Div Hematol & Med Oncol, Dept Urol, New York, NY 10029 USA. [Galsky, Matthew D.] Icahn Sch Med Mt Sinai, Tisch Canc Inst, Div Hematol & Med Oncol, Dept Med, New York, NY 10029 USA. [Sivendran, Shanthi] Lancaster Gen Hlth, LG Hlth Phys Hematol & Med Oncol, Ann B Barshinger Canc Inst, Lancaster, PA USA. RP Sivendran, S (reprint author), Ann B Barshinger Canc Inst, 2102 Harrisburg Pike, Lancaster, PA 17601 USA. EM shanthisivendran@gmail.com FU Bristol-Myers Squibb Company; Novartis Pharmaceutical Corporation; Merck Co. FX Dr. Galsky has received research grants from Bristol-Myers Squibb Company and Novartis Pharmaceutical Corporation and is on the advisory board for and has received research grants from Merck & Co. NR 25 TC 0 Z9 0 U1 1 U2 1 PU QUADRANT HEALTHCOM INC PI PARSIPPANY PA 7 CENTURY DRIVE, STE 302, PARSIPPANY, NJ 07054-4603 USA SN 0011-4162 EI 2326-6929 J9 CUTIS JI Cutis PD SEP PY 2015 VL 96 IS 3 BP 186 EP 190 PG 5 WC Dermatology SC Dermatology GA DB0IL UT WOS:000368191700019 PM 26562269 ER PT J AU Haggerty, G Siefert, CJ Bornstein, RF Sinclair, SJ Blais, MA Zodan, J Rao, N AF Haggerty, Greg Siefert, Caleb J. Bornstein, Robert F. Sinclair, Samuel Justin Blais, Mark A. Zodan, Jennifer Rao, Nyapati TI Correlates of interpersonal dependency and detachment in an adolescent inpatient sample SO BULLETIN OF THE MENNINGER CLINIC LA English DT Article ID RELATIONSHIP PROFILE TEST; CHILD-BEHAVIOR CHECKLIST; HEALTH OUTCOME MEASURE; CONSTRUCT-VALIDITY; PERSONALITY-DISORDER; PSYCHOLOGICAL HEALTH; INITIAL-VALIDATION; GENDER-DIFFERENCES; URBAN WOMEN; ATTACHMENT AB Interpersonal dependency has been linked to psychological distress, depression, help seeking, treatment compliance, and sensitivity to interpersonal cues in adult samples. However, there is a dearth of research focusing on dependency in child and adolescent samples. The current study examined the construct validity of a measure of interpersonal dependency. The authors investigated how interpersonal dependency and detachment relate to behavioral problems, subjective well-being, interpersonal problems, and global symptom severity in adolescent inpatients. Destructive overdependence (DO) and dysfunctional detachment (DD) were positively related to interpersonal distress, behavioral problems, and symptom severity and negatively related to psychological health and well-being. Healthy dependency (HD) was associated with fewer behavioral problems and less symptom severity and positively related to subjective well-being. The clinical implications of these findings are discussed. C1 [Haggerty, Greg; Zodan, Jennifer; Rao, Nyapati] Nassau Univ, Med Ctr, Van Tauber Inst Global Psychiat, E Meadow, NY USA. [Siefert, Caleb J.] Univ Michigan, Dearborn, MI 48128 USA. [Bornstein, Robert F.] Adelphi Univ, Derner Inst Adv Psychol Studies, Garden City, NY USA. [Sinclair, Samuel Justin; Blais, Mark A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sinclair, Samuel Justin; Blais, Mark A.] Harvard Univ, Sch Med, Boston, MA USA. RP Haggerty, G (reprint author), 320 1st Ave, Massapequa Pk, NY 11762 USA. EM ghag541@aol.com FU American Psychoanalytic Association; National Institute of Mental Health (NIMH) [1R21MH097781-01A1] FX This study was supported by a grant awarded to the first author from the American Psychoanalytic Association and supported in part by National Institute of Mental Health (NIMH) Grant No. 1R21MH097781-01A1 received by the first and third authors. NR 65 TC 0 Z9 0 U1 1 U2 4 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 FAL PY 2015 VL 79 IS 4 BP 281 EP 304 PG 24 WC Psychiatry; Psychology, Psychoanalysis SC Psychiatry; Psychology GA DA2PQ UT WOS:000367638700001 PM 26682828 ER PT J AU Sinclair, SJ Walsh-Messinger, J Siefert, CJ Antonius, D Baity, MR Haggerty, G Stein, MB Blais, MA AF Sinclair, Samuel Justin Walsh-Messinger, Julie Siefert, Caleb J. Antonius, Daniel Baity, Matthew R. Haggerty, Greg Stein, Michelle B. Blais, Mark A. TI Neuropsychological functioning and profile validity on the Personality Assessment Inventory (PAI): An investigation in multiple psychiatric settings SO BULLETIN OF THE MENNINGER CLINIC LA English DT Article ID PSYCHOMETRIC PROPERTIES; NORMATIVE DATA; INJURY; TRAIL; LEVEL AB Psychologists in medical settings are frequently tasked with providing comprehensive evaluations of patients with complex medical and psychiatric conditions. In order to achieve these aims, standardized measures of neurocognitive and psychological functioning are often employed to empirically assess a patient's level of functioning across an array of relevant clinical domains. However, less is known about the degree to which cognitive impairment affects a patient's ability to complete these more cornprehensive assessments, raising questions about test validity. The current study sought to contribute to this growing body of literature by examining whether neurocognitive functioning is associated with profile validity on the Personality Assessment Inventory (PAI) in both outpatient (N = 321) and inpatient (N = 131) psychiatric settings. In Study 1, results indicate that while multiple cognitive domains are associated with overall profile validity in psychiatric outpatients, attentional impairment specifically was found to be a significant predictor of profile invalidity after accounting for the effects of overall intellectual functioning (accounting for 13% of the variance overall). The magnitude of attentional impairment specifically, and number of impaired cognitive domains more generally, were also found to be meaningfully associated with overall profile validity. Likewise, in Study 2, PAI profile validity was found to be meaningfully associated with gross cognitive impairment on the WMS-IV Brief Cognitive Status Examination (BCSE) in an inpatient psychiatric setting, with almost half of the patients in the most impaired group yielding invalid PAI profiles. The clinical implications of these findings are discussed. C1 [Sinclair, Samuel Justin; Walsh-Messinger, Julie; Stein, Michelle B.; Blais, Mark A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Sinclair, Samuel Justin; Walsh-Messinger, Julie; Stein, Michelle B.; Blais, Mark A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Siefert, Caleb J.] Univ Michigan, Dept Behav Sci, Dearborn, MI 48128 USA. [Antonius, Daniel] SUNY Buffalo, Sch Med & Biomed Sci, Buffalo, NY USA. [Antonius, Daniel] NYU, Sch Med, Dept Psychiat, New York, NY USA. [Baity, Matthew R.] Alliant Int Univ, Sacramento, CA USA. [Haggerty, Greg] Nassau Univ, Med Ctr, Von Tauber Inst Global Psychiat, E Meadow, NY USA. RP Sinclair, SJ (reprint author), Massachusetts Gen Hosp, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM SJSinclair@MGH.Harvard.Edu NR 44 TC 1 Z9 1 U1 0 U2 6 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 FAL PY 2015 VL 79 IS 4 BP 305 EP 334 PG 30 WC Psychiatry; Psychology, Psychoanalysis SC Psychiatry; Psychology GA DA2PQ UT WOS:000367638700002 PM 26682829 ER PT J AU Sacks, GD Lawson, EH Dawes, AJ Russell, MM Maggard-Gibbons, M Zingmond, DS Ko, CY AF Sacks, Greg D. Lawson, Elise H. Dawes, Aaron J. Russell, Marcia M. Maggard-Gibbons, Melinda Zingmond, David S. Ko, Clifford Y. TI Relationship Between Hospital Performance on a Patient Satisfaction Survey and Surgical Quality SO JAMA SURGERY LA English DT Article ID CLINICAL-QUALITY; MORTALITY-RATES; HEALTH OUTCOMES; CLAIMS DATA; ACS NSQIP; CARE; COMPLICATIONS; PERSPECTIVES; PERCEPTION; EXPERIENCE AB IMPORTANCE The Centers for Medicare and Medicaid Services include patient experience as a core component of its Value-Based Purchasing program, which ties financial incentives to hospital performance on a range of quality measures. However, it remains unclear whether patient satisfaction is an accurate marker of high-quality surgical care. OBJECTIVE To determine whether hospital performance on a patient satisfaction survey is associated with objective measures of surgical quality. DESIGN, SETTING, AND PARTICIPANTS Retrospective observational study of participating American College of Surgeons National Surgical Quality Improvement Project (ACS NSQIP) hospitals. We used data from a linked database of Medicare inpatient claims, ACS NSQIP, the American Hospital Association annual survey, and Hospital Compare from December 2, 2004, through December 31, 2008. A total of 103 866 patients older than 65 years undergoing inpatient surgery were included. Hospitals were grouped by quartile based on their performance on the Hospital Consumer Assessment of Healthcare Providers and Systems survey. Controlling for preoperative risk factors, we created hierarchical logistic regression models to predict the occurrence of adverse postoperative outcomes based on a hospital's patient satisfaction scores. MAIN OUTCOMES AND MEASURES Thirty-day postoperative mortality, major and minor complications, failure to rescue, and hospital readmission. RESULTS Of the 180 hospitals, the overall mean patient satisfaction score was 68.0% (first quartile mean, 58.7%; fourth quartile mean, 76.7%). Compared with patients treated at hospitals in the lowest quartile, those at the highest quartile had significantly lower risk-adjusted odds of death (odds ratio = 0.85; 95% CI, 0.73-0.99), failure to rescue (odds ratio = 0.82; 95% CI, 0.70-0.96), and minor complication (odds ratio = 0.87; 95% CI, 0.75-0.99). This translated to relative risk reductions of 11.1%(P = .04), 12.6%(P = .02), and 11.5%(P = .04), respectively. No significant relationship was noted between patient satisfaction and either major complication or hospital readmission. CONCLUSIONS AND RELEVANCE Using a national sample of hospitals, we demonstrated a significant association between patient satisfaction scores and several objective measures of surgical quality. Our findings suggest that payment policies that incentivize better patient experience do not require hospitals to sacrifice performance on other quality measures. C1 [Sacks, Greg D.; Lawson, Elise H.; Dawes, Aaron J.; Russell, Marcia M.; Maggard-Gibbons, Melinda; Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Sacks, Greg D.; Lawson, Elise H.; Dawes, Aaron J.; Russell, Marcia M.; Maggard-Gibbons, Melinda; Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Zingmond, David S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Sacks, GD (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 10833 Le Conte Ave,72-215 CHS, Los Angeles, CA 90095 USA. EM gsacks@mednet.ucla.edu OI Dawes, Aaron/0000-0003-4574-6765 FU Robert Wood Johnson Foundation Clinical Scholars Program at the University of California, Los Angeles FX Drs Sacks and Dawes were supported by the Robert Wood Johnson Foundation Clinical Scholars Program at the University of California, Los Angeles. NR 38 TC 12 Z9 12 U1 2 U2 7 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 SEP PY 2015 VL 150 IS 9 BP 858 EP 864 DI 10.1001/jamasurg.2015.1108 PG 7 WC Surgery SC Surgery GA DA1VR UT WOS:000367584100008 PM 26108091 ER PT J AU Velmahos, GC AF Velmahos, George C. TI Brain Injury Guidelines for Small Head Injuries SO JAMA SURGERY LA English DT Editorial Material C1 [Velmahos, George C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. RP Velmahos, GC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Ste 810, Boston, MA 02114 USA. EM gvelmahos@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 SEP PY 2015 VL 150 IS 9 BP 872 EP 873 DI 10.1001/jamasurg.2015.1148 PG 3 WC Surgery SC Surgery GA DA1VR UT WOS:000367584100011 PM 26107377 ER PT J AU Amri, R Bordeianou, LG Sylla, P Berger, DL AF Amri, Ramzi Bordeianou, Liliana G. Sylla, Patricia Berger, David L. TI Association of Radial Margin Positivity With Colon Cancer SO JAMA SURGERY LA English DT Article ID TOTAL MESORECTAL EXCISION; RECTAL-CANCER; CIRCUMFERENTIAL MARGIN; OUTCOMES; SURGERY; INVOLVEMENT AB IMPORTANCE In colon cancer, radial margin positivity (RMP) is defined as primary disease involvement at the cut edge of the mesentery or nonserosalized portions of the colon. Although extensively studied for rectal malignancies, RMP has unclear prognostic implications for tumors of the colon. OBJECTIVE To determine the effect of RMP on perioperative outcomes as well as survival and disease-free survival in colon cancer. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study including all patients with surgically treated colon cancer at a tertiary care center from January 1, 2004, through December 31, 2011. The cohort was retrospectively extracted from an institutional patient data repository and included in a data repository maintained prospectively starting June 1, 2011, to April 1, 2014. Participants included 984 patients with surgical colon cancer in the given period, excluding patients with intramucosal tumors (n = 47), palliative resections (n = 24), and patients where radial margin status was not assessable (n = 16). MAIN OUTCOMES AND MEASURES Surgical characteristics, postoperative staging, and long-term outcomes, including recurrence and disease-free survival. RESULTS Of the 984 included cases, 52 (5.3%) had an involved radial margin. Patients with RMP had much higher rates of multivisceral resection (40.4% vs 12.8%; relative risk, 3.16 [95% CI, 2.18-4.58]; P < .001) and conversion (50.0% vs 13.7%; relative risk, 3.78 [95% CI, 1.56-9.18]; P = .01). All patients with RMP had American Joint Committee on Cancer stage II cancer or higher, with higher rates of node positivity (86.5% vs 38.8%; relative risk, 2.23 [95% CI, 1.95-2.55]; P < .001), metastasis (34.6% vs 6.7%; relative risk, 5.20 [95% CI, 3.34-8.11]; P < .001), extramural vascular invasion (76.9% vs 28.4%; relative risk, 2.71 [95% CI, 2.26-3.24]; P < .001), and high-grade tumor (45.1% vs 18.2%; relative risk, 3.01 [95% CI, 2.44-3.88]; P < .001). In patients without baseline metastasis, metastatic disease in follow-up was considerably higher in patients with RMP (37.5% vs 12.5%; relative risk, 3.32 [95% CI, 2.79-3.95]; P < .001), especially peritoneal (18.8% vs 2.6%; relative risk, 7.24 [95% CI, 2.40-21.8]; P < .001) and liver (18.8% vs 6%; relative risk, 3.10 [95% CI, 1.08-8.92]; P = .04) metastasis. In multivariable Cox regression, the hazard ratio for survival adjusted for baseline staging, age, comorbidity, smoking, and neoadjuvant chemotherapy was higher (hazard ratio, 3.39; 95% CI, 2.41-4.77; P < .001) compared with metastasis adjusted for baseline staging, smoking, and neoadjuvant chemotherapy (hazard ratio, 2.03; 95% CI, 1.43-2.89; P < .001). The median follow-up duration for patients alive on April 1, 2014, was 51 months (interquartile range, 33-76 months). CONCLUSIONS AND RELEVANCE An involved radial margin leads to high rates of conversion and multivisceral resection. Although occurring infrequently, RMP is an important stage-independent outcome predictor strongly associated with recurrence, risk of death, and shorter survival. Preoperative assessment, especially imaging, could play a key role in the timely identification of potential patients with RMP to take adequate preparatory surgical and therapeutic measures. C1 [Amri, Ramzi; Bordeianou, Liliana G.; Sylla, Patricia; Berger, David L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Surg & Gastrointestinal Surg, Boston, MA USA. RP Berger, DL (reprint author), Massachusetts Gen Hosp, Div Gen Surg & Gastrointestinal Surg, 15 Parkman St, Boston, MA 02114 USA. EM dberger@mgh.harvard.edu OI Amri, Ramzi/0000-0001-7416-6650 FU National Institutes of Health [8UL1TR000170-05]; National Center for Research Resources; National Center for Advancing Translational Sciences; Dutch Cancer Society; Dutch Digestive Foundation; Amsterdam University Funds; Fulbright Foundation; Harvard University and its affiliated academic health care centers; Harvard Catalyst FX This work was conducted with support from grant 8UL1TR000170-05 from the National Institutes of Health, Harvard Catalyst, the National Center for Research Resources, National Center for Advancing Translational Sciences, Dutch Cancer Society, Dutch Digestive Foundation, Amsterdam University Funds, Fulbright Foundation, and financial contributions from Harvard University and its affiliated academic health care centers. NR 14 TC 4 Z9 4 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 SEP PY 2015 VL 150 IS 9 BP 890 EP 898 DI 10.1001/jamasurg.2015.1525 PG 9 WC Surgery SC Surgery GA DA1VR UT WOS:000367584100015 PM 26132363 ER PT J AU Baladi, MG Neto, RRCMT Cortes, ARG Aoki, EM Arita, ES Freitas, CF AF Baladi, Marina G. Tucunduva Neto, Raul R. C. M. Cortes, Arthur R. G. Aoki, Eduardo M. Arita, Emiko S. Freitas, Claudio F. TI Ultrasound analysis of mental artery flow in elderly patients: a case-control study SO DENTOMAXILLOFACIAL RADIOLOGY LA English DT Article DE Doppler ultrasonography; mental artery; edentulism ID CERVICAL LYMPH-NODES; DOPPLER SONOGRAPHY; ULTRASONOGRAPHY; OSTEOPOROSIS AB Objectives: Mental artery flow decreases with age and may have an aetiological role in alveolar ridge atrophy. The aim of this study was to identify factors associated with alterations of mental artery flow, assessed by ultrasonography. Methods: This case control study was conducted on elderly patients (aged above 60 years) at the beginning of dental treatment. Intraoral B-mode Doppler ultrasonography was used to assess mental artery flow. The cases were defined as patients with a weak/absent ultrasound signal, whereas the controls presented a strong ultrasound signal. Demographics and radiographic findings (low bone mineral density on dual-energy X-ray absorptiometry and mandibular cortical index on panoramic radiographs) were analysed as risk factors for weak/absent ultrasound signal and were calculated as adjusted odds ratios (AORs) with 95% confidence intervals (CIs) using conditional logistic regression. In addition, the Student's t-test was used to compare the mean alveolar bone height of the analysed groups. A p-value <0.05 was considered statistically significant. Results: A total of 30 ultrasound examinations (12 cases and 18 controls) were analysed. A weak/absent mental artery pulse strength was significantly associated with edentulism (AOR = 3.67; 95% CI = 0.86-15.63; p = 0.046). In addition, there was a significant difference in alveolar bone height between edentulous cases and controls (p = 0.036). Conclusions: Within the limitations of this study, the present results indicate that edentulism is associated with diminished mental artery flow, which, in turn, affects alveolar bone height. C1 [Baladi, Marina G.; Tucunduva Neto, Raul R. C. M.; Aoki, Eduardo M.; Arita, Emiko S.; Freitas, Claudio F.] Univ Sao Paulo, Sch Dent, Oral Radiol Div, Sao Paulo, Brazil. [Cortes, Arthur R. G.] Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Cortes, Arthur R. G.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Cortes, ARG (reprint author), Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM acortes@nmr.mgh.harvard.edu RI Cortes, Arthur/C-8738-2013; OI Cortes, Arthur/0000-0001-6591-7256; de Freitas, Claudio Froes/0000-0002-0320-8232 FU National Council for Scientific and Technological Development (CNPq)-Science without Borders, Brazil [232643/2013-0] FX A post-doctoral scholarship was granted to ARGC by the National Council for Scientific and Technological Development (CNPq)-Science without Borders, Brazil, no. 232643/2013-0. NR 22 TC 0 Z9 0 U1 0 U2 0 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0250-832X EI 1476-542X J9 DENTOMAXILLOFAC RAD JI Dentomaxillofac. Radiol. PD SEP PY 2015 VL 44 IS 9 AR 20150097 DI 10.1259/dmfr.20150097 PG 5 WC Dentistry, Oral Surgery & Medicine; Radiology, Nuclear Medicine & Medical Imaging SC Dentistry, Oral Surgery & Medicine; Radiology, Nuclear Medicine & Medical Imaging GA CZ9KO UT WOS:000367416700006 PM 26205777 ER PT J AU King, G Neilan, TG Cohn, K Gannon, S Bennet, K Clarke, J AF King, G. Neilan, T. G. Cohn, K. Gannon, S. Bennet, K. Clarke, J. TI INTRINSIC VORTEX FORMATION TIME: A UNIQUE ECHOCARDIOGRAPHIC PERFORMANCE INDICATOR SO HEART LA English DT Meeting Abstract CT Annual Conference and AGM of the Irish-Cardiac-Society CY OCT 08-10, 2015 CL Killarney, IRELAND SP Irish Cardiac Soc C1 [King, G.; Gannon, S.; Bennet, K.; Clarke, J.] Eagle Lodge Med Ctr, Limerick, Ireland. [Neilan, T. G.] Aut Even Hosp Kilkenny, Dublin, Ireland. [Cohn, K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2015 VL 101 SU 5 MA 1 BP A1 EP A1 DI 10.1136/heartjnl-2015-308621.1 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CZ9YC UT WOS:000367452800002 ER PT J AU Teo, AKK Gupta, MK Doria, A Kulkarni, RN AF Teo, Adrian Kee Keong Gupta, Manoj K. Doria, Alessandro Kulkarni, Rohit N. TI Dissecting diabetes/metabolic disease mechanisms using pluripotent stem cells and genome editing tools SO MOLECULAR METABOLISM LA English DT Review DE Diabetes; Metabolic disease; Pluripotent stem cells; Genome editing; CRISPR/Cas; Disease modeling ID ZINC-FINGER NUCLEASES; INSULIN-PRODUCING CELLS; BODY-MASS INDEX; HUMAN IPS CELLS; GENE CORRECTION; WIDE ASSOCIATION; IN-VITRO; OBESITY; MUTATIONS; DIFFERENTIATION AB Background: Diabetes and metabolic syndromes are chronic, devastating diseases with increasing prevalence. Human pluripotent stem cells are gaining popularity in their usage for human in vitro disease modeling. With recent rapid advances in genome editing tools, these cells can now be genetically manipulated with relative ease to study how genes and gene variants contribute to diabetes and metabolic syndromes. Scope of review: We highlight the diabetes and metabolic genes and gene variants, which could potentially be studied, using two powerful technologies - human pluripotent stem cells (hPSCs) and genome editing tools - to aid the elucidation of yet elusive mechanisms underlying these complex diseases. Major conclusions: hPSCs and the advancing genome editing tools appear to be a timely and potent combination for probing molecular mechanism(s) underlying diseases such as diabetes and metabolic syndromes. The knowledge gained from these hiPSC-based disease modeling studies can potentially be translated into the clinics by guiding clinicians on the appropriate type of medication to use for each condition based on the mechanism of action of the disease. (C) 2015 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 [Teo, Adrian Kee Keong; Gupta, Manoj K.; Kulkarni, Rohit N.] Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02215 USA. [Teo, Adrian Kee Keong; Gupta, Manoj K.; Kulkarni, Rohit N.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Teo, Adrian Kee Keong] Proteos, Div Discovery Res, Inst Mol & Cell Biol, Singapore 138673, Singapore. [Doria, Alessandro] Harvard Univ, Sch Publ Hlth, Joslin Diabet Ctr, Dept Epidemiol,Sect Epidemiol & Genet, Boston, MA 02215 USA. [Teo, Adrian Kee Keong] Nanyang Technol Univ, Sch Biol Sci, Singapore 637551, Singapore. [Teo, Adrian Kee Keong] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore 117596, Singapore. RP Kulkarni, RN (reprint author), 1 Joslin Pl, Boston, MA 02215 USA. EM drainteo@gmail.com; Manoj.Gupta@joslin.harvard.edu; Alessandro.Doria@joslin.harvard.edu; rohit.kulkarni@joslin.harvard.edu RI Teo, Adrian/A-4009-2013 OI Teo, Adrian/0000-0001-5901-7075 FU NIDDK NIH HHS [R01 DK067536, R01 DK103215, R01 DK055523] NR 105 TC 3 Z9 3 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 SEP PY 2015 VL 4 IS 9 BP 593 EP 604 DI 10.1016/j.molmet.2015.06.006 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CZ9VW UT WOS:000367446200001 PM 26413465 ER PT J AU Manchikanti, L Hammer, MJ Boswell, MV Kaye, AD Hirsch, JA AF Manchikanti, Laxmaiah Hammer, Marvel J. Boswell, Mark V. Kaye, Alan D. Hirsch, Joshua A. TI Survival Strategies for Tsunami of ICD-10-CM for Interventionalists: Pursue or Perish! SO PAIN PHYSICIAN LA English DT Review DE ICD-9-CM (International Classification of Diseases, Ninth revision, Clinical Modification); ICD-10; ICD-10-CM (International Classification of Diseases, 10th Revision); Health Insurance Portability and Accountability Act (HIPAA); Health Information Technology (HIT) ID SUSTAINABLE GROWTH-RATE; PAIN MANAGEMENT; UNITED-STATES; STICK POLICY; METAMORPHOSIS; MEDICINE; CARROT AB The unfunded mandate for the implementation of International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) is scheduled October 1, 2015. The development of ICD-10-CM has been a complicated process. We have endeavored to keep Interventional Pain Management doctors apprised via a variety of related topical manuscripts. The major issues relate to the lack of formal physician participation in its preparation. While the American Health Information Management Association (AHIMA) and American Hospital Association (AHA) as active partners in its preparation. Centers for Medicare and Medicaid Services (CMS) and Centers for Disease Control and Prevention (CDC) are major players; 3M and Blue Cross Blue Shield Association are also involved. The cost of ICD-10-CM implementation is high, similar to the implementation of electronic health records (EHRs), likely consuming substantial resources. While ICD-10, utilized worldwide, includes 14,400 different codes, ICD-10-CM, specific for the United States, has expanded to 144,000 codes, which also includes procedural coding system. It is imperative for physicians to prepare for the mandatory implementation. Conversion from ICD-9-CM to ICD-10-CM coding in interventional pain management is not a conversion of one to one that can be easily obtained from software packages. It is a both a difficult and time-consuming task with each physician, early on, expected to spend on estimation at least 10 minutes per visit on extra coding for established and new patients. For interventional pain physicians, there have been a multitude of changes, including creation of new codes and confusing conversion of existing codes. This manuscript describes a variety of codes that are relevant to interventional pain physicians and often utilized in daily practices. It is our objective that this manuscript will provide coding assistance to interventional pain physicians. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Hammer, Marvel J.] MJH Consulting, Denver, CO USA. [Boswell, Mark V.] Univ Louisville, Dept Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Kaye, Alan D.] LSU Hlth Sci Ctr, New Orleans, LA 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 42 TC 5 Z9 5 U1 1 U2 1 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 SEP-OCT PY 2015 VL 18 IS 5 BP E685 EP E712 PG 28 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA DA0YV UT WOS:000367524400001 PM 26431128 ER PT J AU Simopoulos, TT Manchikanti, L Gupta, S Aydin, SM Kim, CH Solanki, D Nampiaparampil, DE Singh, V Staats, PS Hirsch, JA AF Simopoulos, Thomas T. Manchikanti, Laxmaiah Gupta, Sanjeeva Aydin, Steve M. Kim, Chong Hwan Solanki, Daneshvari Nampiaparampil, Devi E. Singh, Vijay Staats, Peter S. Hirsch, Joshua A. TI Systematic Review of the Diagnostic Accuracy and Therapeutic Effectiveness of Sacroiliac Joint Interventions SO PAIN PHYSICIAN LA English DT Review DE Chronic low back pain; sacroiliac joint pain; sacroiliitis; sacroiliac joint injection; sacroiliac joint dysfunction; thermal radiofrequency; pulsed radiofrequency ID LOW-BACK-PAIN; 2-YEAR FOLLOW-UP; CLINICALLY IMPORTANT DIFFERENCE; INTERLAMINAR EPIDURAL INJECTIONS; RANDOMIZED-CONTROLLED-TRIAL; LUMBAR DISC HERNIATION; LATERAL BRANCH BLOCKS; ACTIVE-CONTROL TRIAL; PERIARTICULAR CORTICOSTEROID TREATMENT; MANAGEMENT SPECIFIC INSTRUMENT AB Background: The sacroiliac joint is well known as a cause of low back and lower extremity pain. Prevalence estimates are 10% to 25% in patients with persistent axial low back pain without disc herniation, discogenic pain, or radiculitis based on multiple diagnostic studies and systematic reviews. However, at present there are no definitive management options for treating sacroiliac joint pain. Objective: To evaluate the diagnostic accuracy and therapeutic effectiveness of sacroiliac joint interventions. Study Design: A systematic review of the diagnostic accuracy and therapeutic effectiveness of sacroiliac joint interventions. Methods: The available literature on diagnostic and therapeutic sacroiliac joint interventions was reviewed. The quality assessment criteria utilized were the Quality Appraisal of Reliability Studies (QAREL) checklist for diagnostic accuracy studies, Cochrane review criteria to assess sources of risk of bias, and Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment (IPM - QRB) criteria for randomized therapeutic trials and Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment for Nonrandomized Studies (IPM - QRBNR) for observational therapeutic assessments. The level of evidence was based on a best evidence synthesis with modified grading of qualitative evidence from Level I to Level V. Data sources included relevant literature published from 1966 through March 2015 that were identified through searches of PubMed and EMBASE, manual searches of the bibliographies of known primary and review articles, and all other sources. Outcome Measures: For the diagnostic accuracy assessment, and for the therapeutic modalities, the primary outcome measure of pain relief and improvement in functional status were utilized. Results: A total of 11 diagnostic accuracy studies and 14 therapeutic studies were included. The evidence for diagnostic accuracy is Level II for dual diagnostic blocks with at least 70% pain relief as the criterion standard and Level III evidence for single diagnostic blocks with at least 75% pain relief as the criterion standard. The evidence for cooled radiofrequency neurotomy in managing sacroiliac joint pain is Level II to III. The evidence for conventional radiofrequency neurotomy, intraarticular steroid injections, and periarticular injections with steroids or botulinum toxin is limited: Level III or IV. Limitations: The limitations of this systematic review include inconsistencies in diagnostic accuracy studies with a paucity of high quality, replicative, and consistent literature. The limitations for therapeutic interventions include variations in technique, variable diagnostic standards for inclusion criteria, and variable results. Conclusion: The evidence for the accuracy of diagnostic and therapeutic effectiveness of sacroiliac joint interventions varied from Level II to Level IV. C1 [Simopoulos, Thomas T.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02445 USA. [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Gupta, Sanjeeva] Bradford Teaching Hosp NHS Fdn Trust, Bradford, W Yorkshire, England. [Aydin, Steve M.] Manhattan Spine & Pain Med, New York, NY USA. [Aydin, Steve M.] Hofstra North Shore LIJ Sch Med, New York, NY USA. [Kim, Chong Hwan] W Virginia Univ, Sch Med, Dept Neurosurg, Div Pain Management, Morgantown, WV 26506 USA. [Solanki, Daneshvari] Univ Texas Med Branch, Galveston, TX 77555 USA. [Nampiaparampil, Devi E.] NYU, Sch Med, New York, NY USA. [Singh, Vijay] Spine Pain Diagnost Associates, Niagara, WI USA. [Staats, Peter S.] Premier Pain Ctr, Shrewsbury, NJ USA. [Staats, Peter S.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA 02445 USA. RP Simopoulos, TT (reprint author), Harvard Univ, Sch Med, Dept Anesthesiol, Beth Israel Deaconess, One Brookline Pl,Ste 105, Boston, MA 02445 USA. EM tsimopou@bidmc.harvard.edu FU Boston Scientific; St Jude; Spinal Modulation; Vertos FX Dr Staats Is a Consultant for Medtronic, Boston Scientific, St Jude, Electrocore Medical, Currently is involved in research funded by Boston Scientific, St Jude, Spinal Modulation, Vertos, NR 207 TC 5 Z9 5 U1 8 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 SEP-OCT PY 2015 VL 18 IS 5 BP E713 EP E756 PG 44 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA DA0YV UT WOS:000367524400002 PM 26431129 ER PT J AU Scott, VCS Haake, DA Churchill, BM Justice, SS Kim, JH AF Scott, Victoria C. S. Haake, David A. Churchill, Bernard M. Justice, Sheryl S. Kim, Ja-Hong TI Intracellular Bacterial Communities: A Potential Etiology for Chronic Lower Urinary Tract Symptoms SO UROLOGY LA English DT Review ID UROPATHOGENIC ESCHERICHIA-COLI; ADULT FEMALE BLADDER; INTERSTITIAL CYSTITIS; OVERACTIVE BLADDER; YOUNG-WOMEN; FOLLOW-UP; INFECTIONS; PATHOGENESIS; DIAGNOSIS; CULTURE AB Patients with persistent lower urinary tract symptoms and negative urine cultures are often difficult to treat. Infection may go undetected in these patients because the concentrations of bacteria in their urine are beneath the threshold of standard urine culture techniques. Empiric treatment may result in temporary relief, followed by recurrent symptoms. Occult and recurrent urinary tract infection may be due to both invasion of the bladder wall by uropathogenic Escherichia coli and the formation of biofilm-like intracellular bacterial communities. This review examines emerging evidence for a role of intracellular bacterial communities in human infection. (C) 2015 Elsevier Inc. C1 [Scott, Victoria C. S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. Hosp Columbus, Res Inst Nationwide Childrens, Ctr Microbial Pathogenesis, Columbus, OH USA. Ohio State Univ, Sch Med, Columbus, OH 43210 USA. RP Scott, VCS (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, 10833 Le Conte Ave,Box 951738, Los Angeles, CA 90095 USA. EM vscott@mednet.ucla.edu RI Justice, Sheryl/E-3329-2011 OI Justice, Sheryl/0000-0002-7059-3759 FU NIAID NIH HHS [U01 AI075565, R21 AI109889] NR 47 TC 7 Z9 7 U1 0 U2 5 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 SEP PY 2015 VL 86 IS 3 BP 425 EP 431 DI 10.1016/j.urology.2015.04.002 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA CY5RA UT WOS:000366463700004 PM 26189137 ER PT J AU Latini, JM AF Latini, Jerilyn M. TI Outcomes of the Endoscopic Treatment of Bladder Neck Contractures in the Orthotopic Neobladder SO UROLOGY LA English DT Editorial Material C1 [Latini, Jerilyn M.] VA Boston Healthcare Syst, Urol, Boston, MA 02130 USA. RP Latini, JM (reprint author), VA Boston Healthcare Syst, Urol, Boston, MA 02130 USA. NR 3 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 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD SEP PY 2015 VL 86 IS 3 BP 616 EP 617 DI 10.1016/j.urology.2015.06.026 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA CY5RA UT WOS:000366463700048 PM 26260742 ER PT J AU Otto, IA Melchels, FPW Zhao, X Randolph, MA Kon, M Breugem, CC Malda, J AF Otto, I. A. Melchels, F. P. W. zhao, X. Randolph, M. A. Kon, M. Breugem, C. C. Malda, J. TI Auricular reconstruction using biofabrication-based tissue engineering strategies SO BIOFABRICATION LA English DT Review DE bioprinting; hydrogel; cartilage ID EAR-SHAPED CARTILAGE; ARTICULAR-CARTILAGE; HYDROGELS; SCAFFOLDS; IMPLANTS; MODEL; CHONDROCYTES; AURICLE; CELLS; REGENERATION AB Auricular malformations, which impose a significant social and psychological burden, are currently treated using ear prostheses, synthetic implants or autologous implants derived from rib cartilage. Advances in the field of regenerative medicine and biofabrication provide the possibility to engineer functional cartilage with intricate architectures and complex shapes using patient-derived or donor cells. However, the development of a successful auricular cartilage implant still faces a number of challenges. These challenges include the generation of a functional biochemical matrix, the fabrication of a customized anatomical shape, and maintenance of that shape. Biofabrication technologies may have the potential to overcome these challenges due to their ability to reproducibly deposit multiple materials in complex geometries in a highly controllable manner. This topical review summarizes this potential of biofabrication technologies for the generation of implants for auricular reconstruction. In particular, it aims to discuss how biofabrication technologies, although still in pre-clinical phase, could overcome the challenges of generating and maintaining the desired auricular shapes. Finally, remaining bottlenecks and future directions are discussed. C1 [Otto, I. A.; Melchels, F. P. W.; zhao, X.; Malda, J.] Univ Med Ctr Utrecht, Dept Orthopaed, NL-3508 GA Utrecht, Netherlands. [Otto, I. A.; Kon, M.; Breugem, C. C.] Univ Med Ctr Utrecht, Dept Plast Reconstruct & Hand Surg, NL-3508 GA Utrecht, Netherlands. [zhao, X.; Randolph, M. A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Plast Surg Res Lab,Div Plast Surg, Cambridge, MA 02138 USA. [Malda, J.] Univ Utrecht, Fac Vet Sci, Dept Equine Sci, NL-3584 CM Utrecht, Netherlands. RP Malda, J (reprint author), Univ Med Ctr Utrecht, Dept Orthopaed, Heidelberglaan 100, NL-3508 GA Utrecht, Netherlands. EM j.malda@umcutrecht.nl RI Randolph, Mark/A-4406-2009; OI Malda, Jos/0000-0002-9241-7676 NR 83 TC 4 Z9 4 U1 4 U2 22 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1758-5082 EI 1758-5090 J9 BIOFABRICATION JI Biofabrication PD SEP PY 2015 VL 7 IS 3 AR 032001 DI 10.1088/1758-5090/7/3/032001 PG 12 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA CY5PY UT WOS:000366460800003 PM 26200941 ER PT J AU Hatch, KM Schultz, T Talamo, JH Dick, HB AF Hatch, Kathryn M. Schultz, Tim Talamo, Jonathan H. Dick, H. Burkhard TI Femtosecond laser-assisted compared with standard cataract surgery for removal of advanced cataracts SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article ID EFFECTIVE PHACOEMULSIFICATION TIME; CLASSIFICATION-SYSTEM-III; RISK-FACTORS; FRAGMENTATION; NUCLEUS AB PURPOSE: To compare effective phacoemulsification time (EPT) for the removal of brunescent cataracts treated with femtosecond laser assisted cataract surgery with standard cataract phacoemulsification techniques. SETTING: Ruhr University Eye Hospital, Bochum, Germany. DESIGN: Comparative prospective case study. METHODS: The Lens Opacities Classification System III (LOCS III) grading system was used to measure eyes divided into 4 groups having cataract surgery. Groups 1 and 2 contained eyes with LOCS III grade nuclear opalescence (NO) 3 cataracts treated with standard cataract surgery and femtosecond laser assisted cataract surgery, respectively. Groups 3 and 4 contained brunescent cataracts, LOCS III grades NO5, treated with standard cataract surgery and femtosecond laser assisted cataract surgery, respectively. RESULTS: There were 240 eyes, with 60 eyes in each group. The EPT in Group 1 ranged from 0.46 to 3.10 (mean 1.38); the EPT in all eyes in Group 2 was 0 (P<.001). The EPT in Groups 3 and 4 was 2.12 to 19.29 (mean 6.85) and 0 to 6.75 (mean 1.35), respectively (P<.001). A comparison between EPT in Groups 1 and 4 showed that EPT in Group 4 was also lower than in Group 1 (P =.013). Groups 4 and 1 were the most statistically similar of all groups compared, suggesting that EPT for a femtosecond laser treated grade 5 cataract was most similar to that of a standard-treated grade 3 cataract. CONCLUSION: Femtosecond laser pretreatment for brunescent cataracts allowed for a significant reduction in EPT compared with manual standard phacoemulsification techniques. C1 [Hatch, Kathryn M.; Talamo, Jonathan H.] Harvard Univ, Sch Med, Dept Ophthalmol, Waltham, MA USA. Massachusetts Eye & Ear Infirm, Waltham, MA USA. [Schultz, Tim; Dick, H. Burkhard] Ruhr Univ Bochum, Hosp Eye, Inst Vis Sci, Bochum, Germany. RP Hatch, KM (reprint author), 1601 Trapelo Rd,Suite 184, Waltham, MA 02451 USA. EM kathryn_hatch@meei.harvard.edu NR 19 TC 9 Z9 9 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0886-3350 EI 1873-4502 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD SEP PY 2015 VL 41 IS 9 BP 1833 EP 1838 DI 10.1016/j.jcrs.2015.10.040 PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA CY2KN UT WOS:000366237600007 PM 26603391 ER PT J AU Deipolyi, A Oklu, R AF Deipolyi, Amy Oklu, Rahmi TI Circulating tumor cells and cholangiocarcinoma SO TRANSLATIONAL GASTROINTESTINAL CANCER LA English DT Editorial Material ID ADHESION MOLECULE; COLORECTAL-CANCER; BREAST-CANCER; SURVIVAL; PROGRESSION; CARCINOMA; BLOOD C1 [Deipolyi, Amy] NYU, Dept Radiol, Med Ctr, Div Vasc & Intervent Radiol, New York, NY 10016 USA. [Oklu, Rahmi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Intervent Radiol, Boston, MA USA. [Oklu, Rahmi] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Biomat Innovat Res Ctr, Cambridge, MA 02138 USA. RP Oklu, R (reprint author), Massachusetts Gen Hosp, Div Vasc & Intervent Radiol, 55 Fruit St,290 Gray Bigelow, Boston, MA 02114 USA. EM rahmioklu@gmail.com NR 15 TC 0 Z9 0 U1 1 U2 1 PU AME PUBL CO PI SHEUNG WAN PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG 00000, PEOPLES R CHINA SN 2224-476X EI 2224-4778 J9 TRANSL GASTROIN CANC JI Transl. Gastrointestin. Cancer PD SEP PY 2015 VL 4 IS 5 BP 399 EP 400 DI 10.3978/j.issn.2224-4778.2015.09.02 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CY9RS UT WOS:000366744600014 ER PT J AU Feeney, ER Chung, RT Yazdanpanah, Y AF Feeney, Eoin R. Chung, Raymond T. Yazdanpanah, Yazdan TI Current guidelines and prioritizing treatment of hepatitis C virus in HIV-infected patients SO CURRENT OPINION IN HIV AND AIDS LA English DT Review DE cirrhosis; direct acting antivirals; hepatitis C virus; HIV ID HCV GENOTYPE 1; HUMAN-IMMUNODEFICIENCY-VIRUS; DACLATASVIR PLUS SOFOSBUVIR; COST-EFFECTIVENESS; COINFECTED PATIENTS; PEGYLATED INTERFERON; VIROLOGICAL RESPONSE; FREE REGIMENS; RIBAVIRIN; TELAPREVIR AB Purpose of reviewCoinfection with hepatitis C virus (HCV) and HIV is a significant public health problem worldwide. The broad spectrum antivirals interferon-alpha (IFN) and ribavirin (RBV) have lower sustained virologic response rates in HIV-HCV coinfection compared with HCV monoinfection, with significant associated toxicities and prolonged treatment courses. The recent availability of direct acting antivirals (DAA) has transformed the treatment of HCV, with the opportunity of cure available for most patients with much more tolerable regimens. These regimens are now being studied in HIV-HCV coinfection.Recent findingsDAA-based regimens for HIV-HCV coinfection have shown excellent efficacy, with cure rates similar to HCV monoinfection. Either in combination with IFN and RBV, or in IFN-free' regimens, cure rates of over 90% are the goal for all HIV-HCV-infected individuals. Data are excellent in genotype 1 infection, but further data on genotype 2-6 are required. These regimens have been shown to be cost-effective in HCV monoinfection, and are likely to be cost-effective in HIV-HCV coinfection. Nonetheless they remain expensive. Recent guidelines have identified coinfected patients as a group for prioritization for treatment, regardless of fibrosis stage. Earlier treatment of those likely to transmit HCV is also recommended.SummaryWith the use of DAA, HCV infection in HIV should be curable for most patients, and HIV-infected patients should be prioritized for treatment. The optimal treatment regimens for some genotypes have yet to be determined. The significant cost of DAA-containing regimens is likely to significantly impair their widespread use for the short to medium term, even in well resourced settings, and those with more advanced liver disease are likely to access them first. C1 [Feeney, Eoin R.] Univ Coll Dublin, HIV Mol Res Grp, Dublin 4, Ireland. [Chung, Raymond T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Yazdanpanah, Yazdan] Hop Bichat Claude Bernard, Serv Malad Infect & Trop, F-75877 Paris 18, France. [Yazdanpanah, Yazdan] INSERM, IAME, UMR 1137, Paris, France. [Yazdanpanah, Yazdan] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France. RP Feeney, ER (reprint author), Univ Coll Dublin, Sch Med & Med Sci, HIV Mol Res Grp, Dublin 4, Ireland. EM eoin.feeney@ucd.ie FU Harvard University Center for AIDS Research (HU CFAR NIH/NIAID) [5P30AI060354-09]; French Agence Nationale de Recherche sur le Sida et les Hepatites virales (ANRS); Gilead; Merck; BMS; Abbvie; Mass Biologics FX E.F. is supported by Harvard University Center for AIDS Research (HU CFAR NIH/NIAID fund 5P30AI060354-09). Y.Y. is supported by French Agence Nationale de Recherche sur le Sida et les Hepatites virales (ANRS). R.T.C. has received grant support from Gilead, Merck, BMS, Abbvie and Mass Biologics. NR 42 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1746-630X EI 1746-6318 J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD SEP PY 2015 VL 10 IS 5 BP 323 EP 329 DI 10.1097/COH.0000000000000178 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CX3TZ UT WOS:000365623600005 PM 26248119 ER PT J AU Reinshagen, C Redjal, N Molcanyi, M Rieger, B AF Reinshagen, Clemens Redjal, Navid Molcanyi, Marek Rieger, Bernhard TI Surgical Approaches to the Lumbar Hidden Zone: Current Strategies and Future Directions SO EBIOMEDICINE LA English DT Editorial Material ID DISC HERNIATION; MIGRATION C1 [Reinshagen, Clemens] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Redjal, Navid] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. [Molcanyi, Marek] Univ Cologne, Fac Med, Inst Neurophysiol, D-50931 Cologne, Germany. [Rieger, Bernhard] Univ Dresden, Dept Neurosurg, Dresden, Germany. RP Reinshagen, C (reprint author), Massachusetts Gen Hosp, Dept Radiol, Bldg 149,Room 5404, Charlestown, MA 02129 USA. EM clemens.reinshagen@gmx.de OI Reinshagen, Clemens/0000-0002-8524-4578 NR 11 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2352-3964 J9 EBIOMEDICINE JI EBioMedicine PD SEP PY 2015 VL 2 IS 9 BP 1005 EP 1007 DI 10.1016/j.ebiom.2015.09.010 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA CX8MK UT WOS:000365957600002 PM 26501088 ER PT J AU Leu, C Balestrini, S Maher, B Hernandez-Hernandez, L Gormley, P Hamalainen, E Heggeli, K Schoeler, N Novy, J Willis, J Plagnol, V Ellis, R Reavey, E O'Regan, M Pickrell, WO Thomas, RH Chung, SK Delanty, N McMahon, JM Malone, S Sadleir, LG Berkovic, SF Nashef, L Zuberi, SM Rees, MI Cavalleri, GL Sander, JW Hughes, E Cross, JH Scheffer, IE Palotie, A Sisodiya, SM AF Leu, Costin Balestrini, Simona Maher, Bridget Hernandez-Hernandez, Laura Gormley, Padhraig Hamalainen, Eija Heggeli, Kristin Schoeler, Natasha Novy, Jan Willis, Joseph Plagnol, Vincent Ellis, Rachael Reavey, Eleanor O'Regan, Mary Pickrell, William O. Thomas, Rhys H. Chung, Seo-Kyung Delanty, Norman McMahon, Jacinta M. Malone, Stephen Sadleir, Lynette G. Berkovic, Samuel F. Nashef, Lina Zuberi, Sameer M. Rees, Mark I. Cavalleri, Gianpiero L. Sander, Josemir W. Hughes, Elaine Cross, J. Helen Scheffer, Ingrid E. Palotie, Aarno Sisodiya, Sanjay M. TI Genome-wide Polygenic Burden of Rare Deleterious Variants in Sudden Unexpected Death in Epilepsy SO EBIOMEDICINE LA English DT Article DE Epilepsy; Death; Mortality; Severity; Association; Burden ID TERTIARY REFERRAL CENTER; MOUSE MODEL; SEIZURES; SUDEP; RISK; ASSOCIATION; PREVENTION; MUTATIONS; COHORT AB Sudden unexpected death in epilepsy (SUDEP) represents the most severe degree of the spectrum of epilepsy severity and is the commonest cause of epilepsy-related premature mortality. The precise pathophysiology and the genetic architecture of SUDEP remain elusive. Aiming to elucidate the genetic basis of SUDEP, we analysed rare, protein-changing variants from whole-exome sequences of 18 people who died of SUDEP, 87 living people with epilepsy and 1479 non-epilepsy disease controls. Association analysis revealed a significantly increased genome-wide polygenic burden per individual in the SUDEP cohort when compared to epilepsy (P = 5.7 x 10(-3)) and non-epilepsy disease controls (P = 1.2 x 10(-3)). The polygenic burden was driven both by the number of variants per individual, and over-representation of variants likely to be deleterious in the SUDEP cohort. As determined by this study, more than a thousand genes contribute to the observed polygenic burden within the framework of this study. Subsequent gene-based association analysis revealed five possible candidate genes significantly associated with SUDEP or epilepsy, but no one single gene emerges as common to the SUDEP cases. Our findings provide further evidence for a genetic susceptibility to SUDEP, and suggest an extensive polygenic contribution to SUDEP causation. Thus, an overall increased burden of deleterious variants in a highly polygenic background might be important in rendering a given individual more susceptible to SUDEP. Our findings suggest that exome sequencing in people with epilepsy might eventually contribute to generating SUDEP risk estimates, promoting stratified medicine in epilepsy, with the eventual aim of reducing an individual patient's risk of SUDEP. (C) 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). C1 [Leu, Costin; Balestrini, Simona; Maher, Bridget; Hernandez-Hernandez, Laura; Heggeli, Kristin; Schoeler, Natasha; Willis, Joseph; Sander, Josemir W.; Sisodiya, Sanjay M.] NIHR Univ Coll London Hosp Biomed Res Ctr, UCL Inst Neurol, Dept Clin & Expt Epilepsy, London WC1N 3BG, England. [Balestrini, Simona; Maher, Bridget; Hernandez-Hernandez, Laura; Sander, Josemir W.; Sisodiya, Sanjay M.] Epilepsy Soc, Gerrards Cross, Bucks, England. [Balestrini, Simona] Polytech Univ Marche, Dept Neurosci, Ancona, Italy. [Gormley, Padhraig; Palotie, Aarno] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA USA. [Gormley, Padhraig; Palotie, Aarno] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Gormley, Padhraig; Palotie, Aarno] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Gormley, Padhraig; Palotie, Aarno] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Hamalainen, Eija; Palotie, Aarno] Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland. [Novy, Jan] CHU Vaudois, Dept Clin Neurosci, CH-1011 Lausanne, Switzerland. [Novy, Jan] Univ Lausanne, Lausanne, Switzerland. [Plagnol, Vincent] UCL, Genet Inst, London, England. [Ellis, Rachael; Reavey, Eleanor; O'Regan, Mary; Zuberi, Sameer M.] Royal Hosp Sick Children, Paediat Neurosci Res Grp, Glasgow G3 8SJ, Lanark, Scotland. [Ellis, Rachael; Reavey, Eleanor] So Gen Hosp, West Scotland Genet Serv, Glasgow G51 4TF, Lanark, Scotland. [Pickrell, William O.; Thomas, Rhys H.; Chung, Seo-Kyung; Rees, Mark I.] Swansea Univ, Coll Med, Inst Life Sci, Wales Epilepsy Res Network, Swansea, W Glam, Wales. [Delanty, Norman] Beaumont Hosp, Dept Neurol, Dublin 9, Ireland. [McMahon, Jacinta M.; Berkovic, Samuel F.] Univ Melbourne, Austin Hlth, Dept Med, Melbourne, Vic, Australia. [McMahon, Jacinta M.; Berkovic, Samuel F.; Scheffer, Ingrid E.] Univ Melbourne, Austin Hlth, Dept Neurol, Melbourne, Vic, Australia. [Malone, Stephen] Lady Cilento Childrens Hosp, Dept Neurosci, Brisbane, Qld, Australia. [Sadleir, Lynette G.] Univ Otago, Dept Paediat, Sch Med & Hlth Sci, Wellington, New Zealand. [Nashef, Lina] Kings Coll Hosp London, Dept Neurol, London, England. [Zuberi, Sameer M.] Univ Glasgow, Sch Med, Glasgow, Lanark, Scotland. [Cavalleri, Gianpiero L.] Royal Coll Surgeons Ireland, Mol & Cellular Therapeut Dept, Dublin 2, Ireland. [Hughes, Elaine] Guys & St Thomas NHS Fdn Trust, Evelina Childrens Hosp, Childrens Neurosci, Kings Hlth Partners Acad Hlth Sci Ctr, London, England. [Cross, J. Helen] Great Ormond St Hosp Children NHS Fdn Trust, UCL Inst Child Hlth, London, England. [Cross, J. Helen] Young Epilepsy, Lingfield, England. [Scheffer, Ingrid E.] Univ Melbourne, Dept Paediat, Royal Childrens Hosp, Parkville, Vic 3052, Australia. [Scheffer, Ingrid E.] Florey Inst Neurosci & Mental Hlth, Melbourne, Vic, Australia. [Palotie, Aarno] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Sisodiya, SM (reprint author), NIHR Univ Coll London Hosp Biomed Res Ctr, UCL Inst Neurol, Dept Clin & Expt Epilepsy, 33 Queen Sq, London WC1N 3BG, England. EM s.sisodiya@ucl.ac.uk RI Sander, Josemir/C-1576-2008; Rees, Mark/J-3129-2012; OI Cavalleri, Gianpiero/0000-0002-9802-0506; Sander, Josemir/0000-0001-6041-9661; Leu, Costin/0000-0003-0598-3301; Novy, Jan/0000-0002-6862-7083; Thomas, Rhys/0000-0003-2062-8623; Delaney, Norman/0000-0002-3953-9842; Plagnol, Vincent/0000-0002-5597-9215; Gormley, Padhraig/0000-0002-8908-6968 FU Wellcome Trust [104033] NR 39 TC 11 Z9 11 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2352-3964 J9 EBIOMEDICINE JI EBioMedicine PD SEP PY 2015 VL 2 IS 9 BP 1063 EP 1070 DI 10.1016/j.ebiom.2015.07.005 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA CX8MK UT WOS:000365957600019 PM 26501104 ER PT J AU Kishi, S Campanholle, G Gohil, VM Perocchi, F Brooks, CR Morizane, R Sabbisetti, V Ichimura, T Mootha, VK Bonventre, JV AF Kishi, Seiji Campanholle, Gabriela Gohil, Vishal M. Perocchi, Fabiana Brooks, Craig R. Morizane, Ryuji Sabbisetti, Venkata Ichimura, Takaharu Mootha, Vamsi K. Bonventre, Joseph V. TI Meclizine Preconditioning Protects the Kidney Against Ischemia-Reperfusion Injury SO EBIOMEDICINE LA English DT Article DE Acute kidney injury; Mitochondria; Phosphoethanolamine; Kennedy pathway; Glycolysis; Oxidative phosphorylation ID ACUTE-RENAL-FAILURE; HEMORRHAGIC-SHOCK; OXIDATIVE STRESS; RAT; MITOCHONDRIA; METABOLISM; ACTIVATION; HYPOXIA; MICE; ISCHEMIA/REPERFUSION AB Global or local ischemia contributes to the pathogenesis of acute kidney injury (AKI). Currently there are no specific therapies to prevent AKI. Potentiation of glycolytic metabolism and attenuation of mitochondrial respiration may decrease cell injury and reduce reactive oxygen species generation from the mitochondria. Meclizine, an over-the-counter anti-nausea and -dizziness drug, was identified in a 'nutrient-sensitized' chemical screen. Pretreatment with 100 mg/kg of meclizine, 17 h prior to ischemia protected mice from IRI. Serum creatinine levels at 24 h after IRI were 0.13 +/- 0.06 mg/dl (sham, n = 3), 1.59 +/- 0.10 mg/dl (vehicle, n = 8) and 0.89 +/- 0.11 mg/dl (meclizine, n = 8). Kidney injury was significantly decreased in meclizine treated mice compared with vehicle group (p < 0.001). Protection was also seen when meclizine was administered 24 h prior to ischemia. Meclizine reduced inflammation, mitochondrial oxygen consumption, oxidative stress, mitochondrial fragmentation, and tubular injury. Meclizine preconditioned kidney tubular epithelial cells, exposed to blockade of glycolytic and oxidative metabolism with 2-deoxyglucose and NaCN, had reduced LDH and cytochrome c release. Meclizine upregulated glycolysis in glucose-containing media and reduced cellular ATP levels in galactose-containing media. Meclizine inhibited the Kennedy pathway and caused rapid accumulation of phosphoethanolamine. Phosphoethanolamine recapitulated meclizine-induced protection both in vitro and in vivo. (C) 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). C1 [Kishi, Seiji; Campanholle, Gabriela; Brooks, Craig R.; Morizane, Ryuji; Sabbisetti, Venkata; Ichimura, Takaharu; Bonventre, Joseph V.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Renal,Dept Med, Boston, MA 02115 USA. [Bonventre, Joseph V.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Gohil, Vishal M.; Perocchi, Fabiana; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Bonventre, JV (reprint author), Harvard Inst Med, Room 576,4 Blackfan Circle, Boston, MA 02115 USA. EM joseph_bonventre@hms.harvard.edu FU NIDDK NIH HHS [R37 DK039773, R01 DK039773, R01 DK072381, R37 DK39773] NR 51 TC 3 Z9 3 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2352-3964 J9 EBIOMEDICINE JI EBioMedicine PD SEP PY 2015 VL 2 IS 9 BP 1090 EP 1101 DI 10.1016/j.ebiom.2015.07.035 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA CX8MK UT WOS:000365957600022 PM 26501107 ER PT J AU Matejcic, A Vidovic, D Nebergall, A Greene, M Bresina, S Tepic, S Malchau, H Hodge, WA AF Matejcic, Aljosa Vidovic, Dinko Nebergall, Audrey Greene, Meridith Bresina, Stephen Tepic, Slobodan Malchau, Henrik Hodge, William A. TI New cementless fixation in hip arthroplasty: a radiostereometric analysis SO HIP INTERNATIONAL LA English DT Article DE Total hip replacement; Aseptic loosening; Radiostereometric analysis; Fixation; Locking screw stem fixation ID FOLLOW-UP; CONTACT PRESSURES; BONE-RESORPTION; REPLACEMENT; STEMS; PROSTHESIS; STABILITY; IMPLANTS; INVIVO; DEBRIS AB Introduction: Scyon Orthopaedics AG developed a new mode of cementless fixation of the femoral component that provides immediate and permanent anchorage by monocortical locking screws. The aim of this study was to evaluate the stability of the Scyon total hip replacement (THR) stem in-vivo. Methods: A total of 15 patients, with an average age of 50 years had surgery between 2008 and 2011. Each patient received a Scyon THR. Standard questionnaires were completed at each follow-up visit for evaluation of functional outcomes. RSA, patient reported outcomes, and plain radiographic follow-up were obtained at 6 months, 1 year, 2 years, and 5 years postoperatively. Results: The median +/- standard error (SE) stem subsidence (negative y-translation) was 0.07 +/- 0.07 mm at 1 year, 0.05 +/- 0.04 mm at 2 years and 0.04 +/- 0.13 mm at 5 years. The median +/- SE stem rotation (y-rotation) was 0.1 +/- 0.21 degrees at 1 year, 0.51 +/- 0.31 degrees at 2 years and 0.60 +/- 0.37 degrees at 5 years. Plain radiographs showed bone on-growth onto medial aspect of the stem. Median HHS improved from 55 preoperatively to 93 at 1 year and 97 at 5 years. The median UCLA Activity Score improved from 4 preoperatively to 6 at 1 year and 5 years. Conclusions: RSA results indicate that the Scyon stem with its 5 monocortical locking screws is stable at 5 years. Immediate surgical fixation of the stem and bony on-growth onto the femoral component may ultimately decrease the rate of aseptic stem loosening in these THR patients. C1 [Matejcic, Aljosa; Vidovic, Dinko] Univ Hosp Sisters Mercy, Zagreb 10000, Croatia. [Nebergall, Audrey; Greene, Meridith; Malchau, Henrik] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bresina, Stephen; Tepic, Slobodan] Scyon Orthopaed AG, Au, Switzerland. [Hodge, William A.] Eastern Maine Med Ctr, Bangor, ME USA. RP Vidovic, D (reprint author), Univ Hosp Sisters Mercy, Vinogradska Cesta 29, Zagreb 10000, Croatia. EM dinko.vidovic@gmail.com FU Scyon Orthopaedics AG, Au, Switzerland FX Financial support: This study was supported by Scyon Orthopaedics AG, Au, Switzerland. NR 31 TC 0 Z9 0 U1 0 U2 0 PU WICHTIG PUBL PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 1120-7000 EI 1724-6067 J9 HIP INT JI Hip Int. PD SEP-OCT PY 2015 VL 25 IS 5 BP 477 EP 483 DI 10.5301/hipint.5000254 PG 7 WC Orthopedics SC Orthopedics GA CY5VX UT WOS:000366476800017 PM 26044537 ER PT J AU Chen, XQ Wang, LX Loh, DH Colwell, CS Tache, Y Reue, K Arnold, AP AF Chen, Xuqi Wang, Lixin Loh, Dawn H. Colwell, Christopher S. Tache, Yvette Reue, Karen Arnold, Arthur P. TI Sex differences in diurnal rhythms of food intake in mice caused by gonadal hormones and complement of sex chromosomes SO HORMONES AND BEHAVIOR LA English DT Article DE Food intake; Sex differences; Testosterone; Estradiol; Sex chromosomes; Four Core Genotypes; Body composition; Circadian rhythm; Night eating; Obesity; Adiposity ID NIGHT-EATING SYNDROME; OVARIECTOMIZED MICE; METABOLIC SYNDROME; OBESITY; ASSOCIATION; ESTRADIOL; WEIGHT; MOUSE AB We measured diurnal rhythms of food intake, as well as body weight and composition, while varying three major classes of sex-biasing factors: activational and organizational effects of gonadal hormones, and sex chromosome complement (SCC). Four Core Genotypes (FCG) mice, comprising XX and XY gonadal males and XX and XY gonadal females, were either gonad-intact or gonadectomized (GDX) as adults (2.5 months); food intake was measured second-by-second for 7 days starting 5 weeks later, and body weight and composition were measured for 22 weeks thereafter. Gonadal males weighed more than females. GDX increased body weight/fat of gonadal females, but increased body fat and reduced body weight of males. After GDX, XX mice had greater body weight and more fat than XY mice. In gonad-intact mice, males had greater total food intake and more meals than females during the dark phase, but females had more food intake and meals and larger meals than males during the light phase. GDX reduced overall food intake irrespective of gonad type or SCC, and eliminated differences in feeding between groups with different gonads. Diurnal phase of feeding was influenced by all three sex-biasing variables. Gonad-intact females had earlier onset and acrophase (peak) of feeding relative to males. GDX caused a phase-advance of feeding, especially in XX mice, leading to an earlier onset of feeding in GDX XX vs. XY mice, but earlier acrophase in GDX males relative to females. Gonadal hormones and SCC interact in the control of diurnal rhythms of food intake. (C) 2015 Elsevier Inc. All rights reserved. C1 [Chen, Xuqi; Arnold, Arthur P.] Univ Calif Los Angeles, Dept Integrat Biol & Physiol, Los Angeles, CA 90095 USA. [Chen, Xuqi; Loh, Dawn H.; Colwell, Christopher S.; Arnold, Arthur P.] Univ Calif Los Angeles, Brain Res Inst, Neuroendocrinol Lab, Los Angeles, CA 90095 USA. [Wang, Lixin; Tache, Yvette] Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA. [Wang, Lixin; Tache, Yvette] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurobiol Stress, Dept Med,Div Digest Dis, Los Angeles, CA 90095 USA. [Wang, Lixin; Tache, Yvette] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Loh, Dawn H.; Colwell, Christopher S.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Reue, Karen] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA. [Reue, Karen] Univ Calif Los Angeles, David Geffen Sch Med, Inst Mol Biol, Los Angeles, CA 90095 USA. RP Arnold, AP (reprint author), Univ Calif Los Angeles, Dept Integrat Biol & Physiol, 610 Charles Dr South, Los Angeles, CA 90095 USA. EM xuqichen@physci.ucla.edu; LixinWang@mednet.ucla.edu; hloh@mednet.ucla.edu; ccolwell@mednet.ucla.edu; ytache@mednet.ucla.edu; reuek@ucla.edu; arnold@ucla.edu OI Loh, Dawn/0000-0001-7876-5757 FU NIH [DK083561, NS043196, DK041301]; VA Career Scientist Award; O'Keefe Foundation FX Supported by NIH grants DK083561 (APA, XC, KR), NS043196 (APA), DK041301 (YT, Animal Models Core), VA Career Scientist Award (YT), and the O'Keefe Foundation (CSC). Thanks to Rebecca McClusky, Maureen Ruiz-Sundstrom, and Shawn Aarde for assistance. NR 32 TC 4 Z9 4 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0018-506X EI 1095-6867 J9 HORM BEHAV JI Horm. Behav. PD SEP PY 2015 VL 75 BP 55 EP 63 DI 10.1016/j.yhbeh.2015.07.020 PG 9 WC Behavioral Sciences; Endocrinology & Metabolism SC Behavioral Sciences; Endocrinology & Metabolism GA CY1EQ UT WOS:000366149900008 PM 26226656 ER PT J AU Naunheim, MR Sedaghat, AR Lin, DT Bleier, BS Holbrook, EH Curry, WT Gray, ST AF Naunheim, Matthew R. Sedaghat, Ahmad R. Lin, Derrick T. Bleier, Benjamin S. Holbrook, Eric H. Curry, William T. Gray, Stacey T. TI Immediate and Delayed Complications Following Endoscopic Skull Base Surgery SO JOURNAL OF NEUROLOGICAL SURGERY PART B-SKULL BASE LA English DT Article DE complications; skull base surgery; cerebrospinal fluid leak; hypopituitarism; diabetes insipidus ID CEREBROSPINAL-FLUID LEAKS; CRANIOFACIAL RESECTION; MALIGNANT-TUMORS; ENDONASAL; OUTCOMES; REPAIR; EXPERIENCE; PARANASAL; FUTURE AB Objectives To characterize the temporal distribution and resolution rate of postoperative complications from endoscopic skull base surgery. Design Retrospective review of patients undergoing endoscopic resection of paranasal sinus or skull base neoplasm from 2007 to 2013. Setting Massachusetts General Hospital/Massachusetts Eye and Ear Infirmary Cranial Base Center. Participants Fifty-eight consecutive patients. Main Outcome Measures Postoperative complications were categorized as cerebrospinal fluid (CSF) leak, pituitary, orbital, intracranial, or sinonasal. Complications were temporally categorized as "perioperative" (within 1 week), "early" (after 1 week and within 6 months), or "delayed" (after 6 months). Results The most common perioperative complications were diabetes insipidus (19.0%), CSF leak (5.2%), and meningitis (5.2%), with resolution rates of 75%, 100%, and 100%, respectively. Overall, CSF leak occurred in 13.8% of patients and resolved in all cases. A total of 53.8% of all complications were evident within 1 week of surgery. Chronic rhinosinusitis was the most common delayed complication (3.4%). Hypopituitarism and delayed complications were less likely to resolve (p = 0.014 and p = 0.080, respectively). Conclusions Monitoring of complications after endoscopic skull base surgery should focus on neurologic complications and CSF leak in the early postoperative period and development of chronic rhinosinusitis in the long term. Late-onset complications and hypopituitarism are less likely to resolve. C1 [Naunheim, Matthew R.; Sedaghat, Ahmad R.; Lin, Derrick T.; Bleier, Benjamin S.; Holbrook, Eric H.; Gray, Stacey T.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Naunheim, Matthew R.; Sedaghat, Ahmad R.; Lin, Derrick T.; Bleier, Benjamin S.; Holbrook, Eric H.; Gray, Stacey T.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Curry, William T.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Gray, ST (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM stacey_gray@meei.harvard.edu NR 28 TC 3 Z9 3 U1 0 U2 3 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 SEP PY 2015 VL 76 IS 5 BP 390 EP 396 DI 10.1055/s-0035-1549308 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA CY2BR UT WOS:000366214300010 PM 26401482 ER PT J AU Herranz, E Gianni, C Louapre, C Mangeat, G Loggia, M Treaba, CA Govindarajan, ST Ward, N Sloane, JA Klawiter, EC Ouellette, R Catana, C Hooker, JM Kinkel, RP Mainero, C AF Herranz, E. Gianni, C. Louapre, C. Mangeat, G. Loggia, M. Treaba, C. A. Govindarajan, S. T. Ward, N. Sloane, J. A. Klawiter, E. C. Ouellette, R. Catana, C. Hooker, J. M. Kinkel, R. P. Mainero, C. TI C-11-PBR28 MR-PET imaging detects in vivo diffuse inflammation in cortex, deep gray and normal appearing white matter associated with neurodegeneration and clinical disability SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 31st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY OCT 07-10, 2015 CL Barcelona, SPAIN SP European Comm Treatment & Res Multiple Sclerosis C1 [Herranz, E.; Gianni, C.; Louapre, C.; Mangeat, G.; Loggia, M.; Treaba, C. A.; Govindarajan, S. T.; Ward, N.; Klawiter, E. C.; Ouellette, R.; Catana, C.; Hooker, J. M.; Mainero, C.] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Herranz, E.; Gianni, C.; Louapre, C.; Loggia, M.; Treaba, C. A.; Sloane, J. A.; Klawiter, E. C.; Catana, C.; Hooker, J. M.; Mainero, C.] Harvard Univ, Sch Med, Boston, MA USA. [Mangeat, G.] Polytech Montreal, Inst Biomed Engn, Montreal, PQ, Canada. [Sloane, J. A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Klawiter, E. C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Kinkel, R. P.] Univ Calif San Diego, San Diego, CA 92103 USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2015 VL 21 SU 11 MA 109 BP 29 EP 30 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CX5GF UT WOS:000365729400044 ER PT J AU Kappos, L De Stefano, N Chitnis, T Haring, D Tomic, D Meier, DP Sormani, MP AF Kappos, L. De Stefano, N. Chitnis, T. Haering, D. Tomic, D. Meier, D. Piani Sormani, M. P. TI Predictive value of NEDA for disease outcomes over 6 years in patients with RRMS SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 31st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY OCT 07-10, 2015 CL Barcelona, SPAIN SP European Comm Treatment & Res Multiple Sclerosis C1 [Kappos, L.] Univ Basel Hosp, Basel Neurol, Neurol, Dept Med, CH-4031 Basel, Switzerland. [Kappos, L.] Univ Basel Hosp, Basel Neurol, Neurol, Dept Clin Res, CH-4031 Basel, Switzerland. [Kappos, L.] Univ Basel Hosp, Basel Neurol, Neurol, Dept Biomed, CH-4031 Basel, Switzerland. [Kappos, L.] Univ Basel Hosp, Basel Neurol, Neurol, Dept Biomed Engn, CH-4031 Basel, Switzerland. [De Stefano, N.] Univ Siena, I-53100 Siena, Italy. [Chitnis, T.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Chitnis, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Haering, D.; Tomic, D.; Meier, D. Piani] Novartis Pharma AG, Basel, Switzerland. [Sormani, M. P.] Univ Genoa, Genoa, Italy. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2015 VL 21 SU 11 MA 116 BP 33 EP 34 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CX5GF UT WOS:000365729400050 ER PT J AU Chitnis, T Graves, J Weinstock-Guttman, B Belman, A Misra, M Olsen, CS Aaen, G Benson, L Candee, M Gorman, M Greenberg, B Lotze, T Ness, J Rodriguez, M Rose, J Rubin, J Schreiner, T Mendelt-Tillema, J Casper, TC Waubant, E AF Chitnis, T. Graves, J. Weinstock-Guttman, B. Belman, A. Misra, M. Olsen, C. S. Aaen, G. Benson, L. Candee, M. Gorman, M. Greenberg, B. Lotze, T. Ness, J. Rodriguez, M. Rose, J. Rubin, J. Schreiner, T. Mendelt-Tillema, J. Casper, T. C. Waubant, E. CA US Network Pediat MS Ctr TI Effect of obesity and puberty on risk and age at onset of pediatric MS SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 31st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY OCT 07-10, 2015 CL Barcelona, SPAIN SP European Comm Treatment & Res Multiple Sclerosis C1 [Chitnis, T.; Benson, L.; Gorman, M.] Massachusetts Gen Hosp, Partners Pediat MS Ctr, Boston, MA 02114 USA. [Chitnis, T.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Chitnis, T.] Harvard Univ, Sch Med, Boston, MA USA. [Graves, J.; Waubant, E.] Univ Calif San Francisco, UCSF Reg Pediat MS Ctr, San Francisco, CA 94143 USA. [Weinstock-Guttman, B.] SUNY Buffalo, Jacobs Neurol Inst, Pediat MS Ctr, Buffalo, NY 14260 USA. [Belman, A.] SUNY Stony Brook, Dept Neurol, Stony Brook, NY 11794 USA. [Misra, M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Olsen, C. S.; Candee, M.; Casper, T. C.] Univ Utah, Dept Pediat, Salt Lake City, UT USA. [Aaen, G.] Loma Linda Univ, Childrens Hosp, Pediat MS Ctr, Loma Linda, CA 92350 USA. [Greenberg, B.] UT Southwestern, Dept Neurol, Dallas, TX USA. [Lotze, T.] Baylor Coll Med, Blue Bird Circle MS Ctr, Houston, TX 77030 USA. [Ness, J.] Univ Alabama Birmingham, Alabama Pediat MS Ctr, Birmingham, AL USA. [Rodriguez, M.; Mendelt-Tillema, J.] Mayo Clin, Dept Neurol, Rochester, NY USA. [Rose, J.] Univ Utah, Dept Neurol, Salt Lake City, UT USA. [Rubin, J.] Northwestern Univ, Sch Med, Dept Pediat Neurol, Chicago, IL USA. [Schreiner, T.] Univ Colorado, Sch Med, Dept Neurol, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2015 VL 21 SU 11 MA P261 BP 89 EP 89 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CX5GF UT WOS:000365729400152 ER PT J AU Nourbakhsh, B Graves, J Lulu, S Waldman, A Belman, A Greenberg, B Weinstock-Guttman, B Aaen, G Tillema, JM Hart, J Lee, M Ness, J Rubin, J Krupp, L Gorman, M Benson, L Rodriguez, M Chitnis, T Simmons, T Casper, C Rose, J Barcellos, L Waubant, E AF Nourbakhsh, B. Graves, J. Lulu, S. Waldman, A. Belman, A. Greenberg, B. Weinstock-Guttman, B. Aaen, G. Tillema, J. -M. Hart, J. Lee, M. Ness, J. Rubin, J. Krupp, L. Gorman, M. Benson, L. Rodriguez, M. Chitnis, T. Simmons, T. Casper, C. Rose, J. Barcellos, L. Waubant, E. TI Association of dietary salt intake and relapse rate in pediatric multiple sclerosis SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 31st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY OCT 07-10, 2015 CL Barcelona, SPAIN SP European Comm Treatment & Res Multiple Sclerosis C1 [Nourbakhsh, B.; Graves, J.; Lulu, S.; Hart, J.; Lee, M.; Waubant, E.] Univ Calif San Francisco, Neurol, San Francisco, CA 94143 USA. [Waldman, A.] Univ Penn, Neurol, Philadelphia, PA 19104 USA. [Belman, A.; Krupp, L.] SUNY Stony Brook, Neurol, Stony Brook, NY 11794 USA. [Greenberg, B.] UT Southwestern, Dallas, TX USA. [Weinstock-Guttman, B.] SUNY Buffalo, Buffalo, NY 14260 USA. [Aaen, G.] Loma Linda Univ, Loma Linda, CA 92350 USA. [Tillema, J. -M.; Rodriguez, M.] Mayo Clin, Neurol, Rochester, MN USA. [Ness, J.] Alabama Pediat MS Ctr, Birmingham, AL USA. [Rubin, J.] Northwestern Feinberg Sch Med, Chicago, IL USA. [Gorman, M.; Benson, L.; Chitnis, T.] Massachusetts Gen Hosp, Partners Pediat MS Ctr, Boston, MA 02114 USA. [Simmons, T.; Casper, C.] Univ Utah, Pediat, Salt Lake City, UT USA. [Rose, J.] Univ Utah, Neurol, Salt Lake City, UT USA. [Barcellos, L.] Univ Calif Berkeley, Epidemiol, Berkeley, CA USA. NR 0 TC 0 Z9 0 U1 2 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2015 VL 21 SU 11 MA P264 BP 91 EP 91 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CX5GF UT WOS:000365729400155 ER PT J AU Langer-Gould, AM Lucas, R Chen, LH Xiang, A Barcellos, L AF Langer-Gould, A. M. Lucas, R. Chen, L. H. Xiang, A. Barcellos, L. TI Vitamin D, race/ethnicity and the risk of multiple sclerosis SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 31st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY OCT 07-10, 2015 CL Barcelona, SPAIN SP European Comm Treatment & Res Multiple Sclerosis C1 [Langer-Gould, A. M.; Chen, L. H.; Xiang, A.] Kaiser Permanente So Calif, Res & Evaluat, Pasadena, CA 91101 USA. [Langer-Gould, A. M.] W Los Angeles Vet Affairs Med Ctr, Neurol, So Calif Permanente Med Grp, Los Angeles, CA USA. [Lucas, R.] Australian Natl Univ, Natl Ctr Epidemiol & Populat Hlth, Canberra, ACT, Australia. [Barcellos, L.] Univ Calif Berkeley, Sch Publ Hlth, Genet Eopidemiol & Genom Lab QB3, Berkeley, CA 94720 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2015 VL 21 SU 11 MA P280 BP 100 EP 100 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CX5GF UT WOS:000365729400171 ER PT J AU Wenten, M Bhan, I Payas, N Meka, V Novas, M AF Wenten, M. Bhan, I. Payas, N. Meka, V. Novas, M. TI Evidence of an association between multiple sclerosis and renal disease SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 31st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY OCT 07-10, 2015 CL Barcelona, SPAIN SP European Comm Treatment & Res Multiple Sclerosis C1 [Wenten, M.; Payas, N.; Meka, V.; Novas, M.] Biogen, Cambridge, MA USA. [Bhan, I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2015 VL 21 SU 11 MA P289 BP 106 EP 106 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CX5GF UT WOS:000365729400180 ER PT J AU Hughes, AJ Turner, AP Alschuler, KN Beier, M Atkins, D Amtmann, D Ehde, DM AF Hughes, A. J. Turner, A. P. Alschuler, K. N. Beier, M. Atkins, D. Amtmann, D. Ehde, D. M. TI Association between sleep disturbance and perceived cognitive dysfunction over 12 months in individuals living with multiple sclerosis SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 31st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY OCT 07-10, 2015 CL Barcelona, SPAIN SP European Comm Treatment & Res Multiple Sclerosis C1 [Hughes, A. J.; Turner, A. P.; Alschuler, K. N.; Beier, M.; Amtmann, D.; Ehde, D. M.] Univ Washington, Rehabil Med, Seattle, WA 98195 USA. [Hughes, A. J.; Turner, A. P.] VA Puget Sound Hlth Care Syst, MS Ctr Excellence West, Seattle Div, Seattle, WA USA. [Beier, M.] Johns Hopkins, Rehabil Med, Baltimore, MD USA. [Atkins, D.] Univ Washington, Psychiat & Behav Sci, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2015 VL 21 SU 11 MA P302 BP 113 EP 114 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CX5GF UT WOS:000365729400193 ER PT J AU Bermel, RA Yankey, J Novalis, C Schneebaum, J Kaiser, P Coffey, C Cudkowicz, ME Gleason, T Goodman, A Klawiter, EC Matsuda, K McGovern, MM McNeil, E Naismith, R Fox, RJ AF Bermel, R. A. Yankey, J. Novalis, C. Schneebaum, J. Kaiser, P. Coffey, C. Cudkowicz, M. E. Gleason, T. Goodman, A. Klawiter, E. C. Matsuda, K. McGovern, M. M. McNeil, E. Naismith, R. Fox, R. J. TI OCT characteristics at baseline in the SPRINT-MS/NN 102 phase II trial of ibudilast in progressive MS SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 31st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY OCT 07-10, 2015 CL Barcelona, SPAIN SP European Comm Treatment & Res Multiple Sclerosis C1 [Bermel, R. A.; Kaiser, P.; Fox, R. J.] Cleveland Clin, Cleveland, OH 44106 USA. [Yankey, J.; Coffey, C.] Univ Iowa, Iowa City, IA USA. [Novalis, C.; Schneebaum, J.] Digital Angiog Reading Ctr, Great Neck, NY USA. [Cudkowicz, M. E.; Klawiter, E. C.; McGovern, M. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Goodman, A.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Matsuda, K.] Medicinova Inc, San Diego, CA USA. [McNeil, E.] NINDS, Bethesda, MD 20892 USA. [Naismith, R.] Washington Univ, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2015 VL 21 SU 11 MA P498 BP 219 EP 220 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CX5GF UT WOS:000365729400389 ER PT J AU Huang, S Souza, A Choi, JK Tomkinson, B Mandeville, J Dellovade, T AF Huang, S. Souza, A. Choi, J. -K. Tomkinson, B. Mandeville, J. Dellovade, T. TI Therapeutic treatment with ATX-MS-1467 reduces T1-weighted gadolinium leakage volume in a preclinical model of multiple sclerosis SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 31st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY OCT 07-10, 2015 CL Barcelona, SPAIN SP European Comm Treatment & Res Multiple Sclerosis C1 [Huang, S.; Souza, A.; Tomkinson, B.; Dellovade, T.] EMD Serono Res & Dev Inst, Immunol & Neurol, Billerica, MA USA. [Choi, J. -K.; Mandeville, J.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2015 VL 21 SU 11 MA P547 BP 249 EP 249 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CX5GF UT WOS:000365729400438 ER PT J AU Koudriavtseva, T Plantone, D Renna, R Mandoj, C Mainero, C AF Koudriavtseva, T. Plantone, D. Renna, R. Mandoj, C. Mainero, C. TI Interferon-beta therapy and risk of thrombocytopenia in multiple sclerosis patients SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 31st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY OCT 07-10, 2015 CL Barcelona, SPAIN SP European Comm Treatment & Res Multiple Sclerosis C1 [Koudriavtseva, T.; Plantone, D.; Renna, R.] Regina Elena Inst Canc Res, Neurol Unit, Rome, Italy. [Mandoj, C.] Regina Elena Inst Canc Res, Clin Pathol, Rome, Italy. [Mainero, C.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Mainero, C.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2015 VL 21 SU 11 MA P604 BP 288 EP 289 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CX5GF UT WOS:000365729400495 ER PT J AU Koelman, DLH Chahin, S Mar, SS Venkatesan, A Hoganson, GM Yeshokumar, AK Barreras, P Majmudar, B Chitnis, T Mateen, FJ AF Koelman, D. L. H. Chahin, S. Mar, S. S. Venkatesan, A. Hoganson, G. M. Yeshokumar, A. K. Barreras, P. Majmudar, B. Chitnis, T. Mateen, F. J. TI Adult- versus pediatric-onset acute disseminated encephalomyelitis: is there a difference? A retrospective, multi-center cohort study SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 31st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY OCT 07-10, 2015 CL Barcelona, SPAIN SP European Comm Treatment & Res Multiple Sclerosis C1 [Koelman, D. L. H.; Chitnis, T.; Mateen, F. J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Koelman, D. L. H.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. [Chahin, S.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Mar, S. S.; Hoganson, G. M.; Majmudar, B.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Venkatesan, A.; Yeshokumar, A. K.; Barreras, P.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Mateen, F. J.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2015 VL 21 SU 11 MA P753 BP 374 EP 375 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CX5GF UT WOS:000365729401131 ER PT J AU Mazzola, MA Raheja, R Rajabi, H Griffin, R Aly, L Patel, B Weiner, H Gandhi, R AF Mazzola, M. A. Raheja, R. Rajabi, H. Griffin, R. Aly, L. Patel, B. Weiner, H. Gandhi, R. TI TCF-1 regulates T-cell response in multiple sclerosis SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 31st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY OCT 07-10, 2015 CL Barcelona, SPAIN SP European Comm Treatment & Res Multiple Sclerosis C1 [Mazzola, M. A.; Raheja, R.; Griffin, R.; Aly, L.; Patel, B.; Weiner, H.; Gandhi, R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Rajabi, H.] Dana Faber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2015 VL 21 SU 11 MA P891 BP 449 EP 449 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CX5GF UT WOS:000365729401269 ER PT J AU Bireley, JD Huang, SY Tobyne, S Smith, V Boratyn, D Nummenmaa, A Witzel, T Wald, LL Klawiter, EC AF Bireley, J. D. Huang, S. Y. Tobyne, S. Smith, V. Boratyn, D. Nummenmaa, A. Witzel, T. Wald, L. L. Klawiter, E. C. TI Neurite orientation dispersion and density imaging (NODDI) at ultra high gradient strength reveals axon pathology in multiple sclerosis SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 31st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY OCT 07-10, 2015 CL Barcelona, SPAIN SP European Comm Treatment & Res Multiple Sclerosis C1 [Bireley, J. D.; Huang, S. Y.; Tobyne, S.; Smith, V.; Boratyn, D.; Klawiter, E. C.] Massachusetts Gen Hosp, Neurol, Charlestown, MA USA. [Nummenmaa, A.; Witzel, T.; Wald, L. L.] Massachusetts Gen Hosp, Charlestown, MA USA. RI Wald, Lawrence/D-4151-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2015 VL 21 SU 11 MA P965 BP 489 EP 490 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CX5GF UT WOS:000365729401343 ER PT J AU Gartner, J Pohl, D Ghezzi, A Bruck, W Haring, D Karlsson, G Putzki, N Chitnis, T AF Gaertner, J. Pohl, D. Ghezzi, A. Brueck, W. Haering, D. Karlsson, G. Putzki, N. Chitnis, T. TI Disease activity on individual components of "no evidence of disease activity" (NEDA-4) in young adult patients with relapsing-remitting multiple sclerosis SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 31st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY OCT 07-10, 2015 CL Barcelona, SPAIN SP European Comm Treatment & Res Multiple Sclerosis C1 [Gaertner, J.] Univ Med, Dept Pediat & Adolescent Med, Gottingen, Germany. [Pohl, D.] Childrens Hosp Eastern Ontario, Ottawa, ON K1H 8L1, Canada. [Ghezzi, A.] Ctr Studi Sclerosi Multipla, Gallarate, Italy. [Brueck, W.] Univ Med, Dept Neuropathol, Gottingen, Germany. [Haering, D.; Karlsson, G.; Putzki, N.] Novartis Pharma AG, Basel, Switzerland. [Chitnis, T.] Massachusetts Gen Hosp, Partners Pediat Multiple Sclerosis Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2015 VL 21 SU 11 MA P1136 BP 591 EP 591 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CX5GF UT WOS:000365729402001 ER PT J AU Graves, JS Chitnis, T Guttman, BW Rubin, J Nourbakhsh, B Zeilkovitch, A Simmons, T Krupp, L Belman, A Ness, J Mendelt-Tillema, J Rodriguez, M Gorman, M Benson, L Waldman, A Aaen, G Greenberg, B Schreiner, T Rose, J Casper, TC Waubant, E AF Graves, J. S. Chitnis, T. Guttman, B. Weinstock Rubin, J. Nourbakhsh, B. Zeilkovitch, A. Simmons, T. Krupp, L. Belman, A. Ness, J. Mendelt-Tillema, J. Rodriguez, M. Gorman, M. Benson, L. Waldman, A. Aaen, G. Greenberg, B. Schreiner, T. Rose, J. Casper, T. C. Waubant, E. TI Pregnancy exposures and risk for paediatric onset MS SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 31st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY OCT 07-10, 2015 CL Barcelona, SPAIN SP European Comm Treatment & Res Multiple Sclerosis C1 [Graves, J. S.; Nourbakhsh, B.; Waubant, E.] UCSF, San Francisco, CA USA. [Chitnis, T.] Massachusetts Gen Hosp, Partners Pediat MS Ctr, Boston, MA 02114 USA. [Guttman, B. Weinstock] SUNY Buffalo, Buffalo, NY 14260 USA. [Rubin, J.; Zeilkovitch, A.] Northwestern Feinberg Sch Med, Chicago, IL USA. [Simmons, T.] Univ Utah, San Francisco, CA USA. [Krupp, L.; Belman, A.] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Ness, J.] Alabama Pediat MS Ctr, Birmingham, AL USA. [Mendelt-Tillema, J.; Rodriguez, M.] Mayo Clin, Rochester, MN USA. [Gorman, M.; Benson, L.] Boston Childrens Pediat MS Ctr, Boston, MA USA. [Waldman, A.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Aaen, G.] Loma Linda Univ, Loma Linda, CA 92350 USA. [Greenberg, B.] UT Southwestern Med Ctr, Dallas, TX USA. [Schreiner, T.] Univ Colorado, Denver, CO 80202 USA. [Rose, J.; Casper, T. C.] Univ Utah, Salt Lake City, UT USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2015 VL 21 SU 11 MA EP1419 BP 741 EP 742 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CX5GF UT WOS:000365729402283 ER PT J AU Lavery, AM Waldman, AT Roalstad, S Ness, J Gorman, M Benson, L Weinstock-Guttman, B Rubin, J Schreiner, T Aaen, G Tillema, JM Rodriguez, M Chitnis, T Candee, M Krupp, L Belman, A Lotze, T Graves, J Graves, B Mar, S Casper, C Rose, J Simmons, T Waubant, E AF Lavery, A. M. Waldman, A. T. Roalstad, S. Ness, J. Gorman, M. Benson, L. Weinstock-Guttman, B. Rubin, J. Schreiner, T. Aaen, G. Tillema, J. Mendelt Rodriguez, M. Chitnis, T. Candee, M. Krupp, L. Belman, A. Lotze, T. Graves, J. Graves, B. Mar, S. Casper, C. Rose, J. Simmons, T. Waubant, E. TI The geographic distribution of pediatric MS in the US SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 31st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY OCT 07-10, 2015 CL Barcelona, SPAIN SP European Comm Treatment & Res Multiple Sclerosis C1 [Lavery, A. M.; Waldman, A. T.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Roalstad, S.; Casper, C.; Rose, J.; Simmons, T.] Univ Utah, Salt Lake City, UT USA. [Ness, J.] Univ Alabama, Tuscaloosa, AL USA. [Gorman, M.; Benson, L.] Boston Childrens Pediat MS Ctr, Boston, MA USA. [Weinstock-Guttman, B.] SUNY Buffalo, Buffalo Gen Hosp, Buffalo, NY 14260 USA. [Rubin, J.] Lurie Childrens Hosp, Chicago, IL USA. [Schreiner, T.] Denver Childrens Hosp, Denver, CO USA. [Aaen, G.] Loma Linda Univ, Childrens Hosp, Loma Linda, CA 92350 USA. [Tillema, J. Mendelt; Rodriguez, M.] Mayo Clin, Rochester, MN USA. [Chitnis, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Candee, M.] Primary Childrens Med Ctr, Salt Lake City, UT USA. [Krupp, L.; Belman, A.] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Lotze, T.] Texas Childrens Hosp, Houston, TX 77030 USA. [Graves, J.; Waubant, E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Graves, B.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Mar, S.] Washington Univ, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2015 VL 21 SU 11 MA EP1420 BP 742 EP 742 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CX5GF UT WOS:000365729402284 ER PT J AU Fox, RJ Coffey, C Cudkowicz, ME Gleason, T Goodman, A Klawiter, EC Matsuda, K McGovern, MM McNeil, E Naismith, R Yankey, J AF Fox, R. J. Coffey, C. Cudkowicz, M. E. Gleason, T. Goodman, A. Klawiter, E. C. Matsuda, K. McGovern, M. M. McNeil, E. Naismith, R. Yankey, J. TI SPRINT-MS/NN 102 phase II trial of ibudilast in progressive MS: baseline characteristics SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 31st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY OCT 07-10, 2015 CL Barcelona, SPAIN SP European Comm Treatment & Res Multiple Sclerosis C1 [Fox, R. J.] Cleveland Clin, Cleveland, OH 44106 USA. [Coffey, C.; Yankey, J.] Univ Iowa, Iowa City, IA USA. [Cudkowicz, M. E.; Klawiter, E. C.; McGovern, M. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Goodman, A.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Matsuda, K.] Medicinova Inc, San Diego, CA USA. [McNeil, E.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Naismith, R.] Washington Univ, Sch Med, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2015 VL 21 SU 11 MA EP1475 BP 769 EP 770 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CX5GF UT WOS:000365729402339 ER PT J AU Kantar, RS Haddad, AG Tamim, H Jamali, F Taher, AT AF Kantar, Rami S. Haddad, Anthony G. Tamim, Hani Jamali, Faek Taher, Ali T. TI Venous thromboembolism and preoperative steroid use: Analysis of the NSQIP database to evaluate risk in surgical patients SO EUROPEAN JOURNAL OF INTERNAL MEDICINE LA English DT Article DE NSQIP; Venous thromboembolism; Surgery; Glucocorticoids ID PULMONARY-EMBOLISM; GLUCOCORTICOIDS; SURGERY; DEXAMETHASONE; PROGRAM AB Background: Despite several prophylactic strategies, postoperative venous thromboembolism (VTE) remains a major cause of morbidity and mortality. Therefore, the search for modifiable preoperative risk factors is crucial. Few reports have explored this issue but the direct relationship between preoperative steroid use and postoperative VTE in surgical patients remains unexplored. Methods: We used The American College of Surgeons' National Surgical Quality Improvement Program (NSQIP) database in our study. After analyzing patient characteristics, we used multivariate logistic regression to assess the crude and adjusted effect of steroids on VTE, our primary outcome. Results: Data was obtained for 1,921,901 patients, 58,667 of whom were on glucocorticoids for at least 30 days preoperatively. VTE was higher in patients on steroids with an adjusted odds ratio of 1.54, 95% confidence interval (CI) 1.45-1.64. The adjusted odds ratio for the secondary outcomes: mortality, urinary tract occurrences, wound occurrences, sepsis, cardiac and respiratory adverse events were 1.42 (CI 1.35-1.49), 1.40 (CI 1.301.50), 1.58 (CI 1.51-1.66), 1.51 (CI 1.42-1.60), 1.19 (CI 1.11-1.29) and 1.302 (CI 1.301-1.303) respectively. Conclusions: Our results suggest that surgical patients with prolonged preoperative glucocorticoid intake are at a higher risk of developing postoperative VTE as well as other secondary outcomes including: all-cause mortality, urinary tract occurrences, sepsis, wound occurrences, cardiac and respiratory adverse events. These are important findings since preoperative glucocorticoid use is a modifiable factor. (C) 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. C1 [Kantar, Rami S.; Taher, Ali T.] Massachusetts Gen Hosp, Expt Therapeut & Mol Imaging Lab, Boston, MA 02114 USA. [Haddad, Anthony G.; Tamim, Hani] Amer Univ Beirut, Med Ctr, Dept Internal Med, Beirut 11072020, Lebanon. [Jamali, Faek] Amer Univ Beirut, Med Ctr, Dept Surg, Beirut 11072020, Lebanon. [Haddad, Anthony G.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Taher, AT (reprint author), Amer Univ Beirut, Med Ctr, Dept Internal Med, Div Hematol & Oncol, POB 11-0236, Beirut 11072020, Lebanon. EM ataher@aub.edu.lb NR 20 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0953-6205 EI 1879-0828 J9 EUR J INTERN MED JI Eur. J. Intern. Med. PD SEP PY 2015 VL 26 IS 7 BP 528 EP 533 DI 10.1016/j.ejim.2015.06.005 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA CX5UJ UT WOS:000365767700020 PM 26148433 ER PT J AU Cutler, A Harper, L Young, J Adeyi, B Dirks, B Wilens, T AF Cutler, A. Harper, L. Young, J. Adeyi, B. Dirks, B. Wilens, T. TI Guanfacine extended release: daytime sleepiness outcomes from a phase 3 clinical study in adolescents with attention-deficit/hyperactivity disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 28th Congress of the European-College-of-Neuropsychopharmacology (ECNP) CY AUG 29-SEP 01, 2015 CL Amsterdam, NETHERLANDS SP European Coll Neuropsychopharmacol C1 [Cutler, A.] Florida Clin Res Ctr, Bradenton, FL USA. [Harper, L.] CNS Healthcare, Orlando, FL USA. [Young, J.] Rochester Ctr Behav Med, Rochester Hills, MI USA. [Adeyi, B.] Shire, Global Biostat, Wayne, NJ USA. [Dirks, B.] Shire, Clin Dev & Med Affairs, Wayne, NJ USA. [Wilens, T.] Massachusetts Gen Hosp, Div Child & Adolescent Psychiat, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X EI 1873-7862 J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2015 VL 25 SU 2 MA P.7.d.014 BP S648 EP S649 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CX2HS UT WOS:000365518300400 ER PT J AU Jenkins, B AF Jenkins, B. TI Basic concepts of phMRI: interpretation and pitfalls SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 28th Congress of the European-College-of-Neuropsychopharmacology (ECNP) CY AUG 29-SEP 01, 2015 CL Amsterdam, NETHERLANDS SP European Coll Neuropsychopharmacol C1 [Jenkins, B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging Radiol, Charlestown, MA USA. NR 2 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X EI 1873-7862 J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2015 VL 25 SU 2 MA S.10.01 BP S124 EP S124 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CX2HR UT WOS:000365518200041 ER PT J AU Joshi, G Gabrieli, J Biederman, J Whitfield-Gabrieli, S AF Joshi, G. Gabrieli, J. Biederman, J. Whitfield-Gabrieli, S. TI Integration and segregation of default mode network resting-state functional connectivity in high-functioning autism spectrum disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 28th Congress of the European-College-of-Neuropsychopharmacology (ECNP) CY AUG 29-SEP 01, 2015 CL Amsterdam, NETHERLANDS SP European Coll Neuropsychopharmacol C1 [Joshi, G.; Biederman, J.] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Gabrieli, J.; Whitfield-Gabrieli, S.] MIT, Brain & Cognit Sci, Cambridge, MA 02139 USA. NR 4 TC 0 Z9 0 U1 4 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X EI 1873-7862 J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2015 VL 25 SU 2 MA P.1.b.022 BP S190 EP S191 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CX2HR UT WOS:000365518200174 ER PT J AU Petryshen, T Blokland, G AF Petryshen, T. Blokland, G. TI Investigating schizophrenia genome-wide association studies risk variants in cognitive and neuroimaging defects in the GENUS Consortium collection SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 28th Congress of the European-College-of-Neuropsychopharmacology (ECNP) CY AUG 29-SEP 01, 2015 CL Amsterdam, NETHERLANDS SP European Coll Neuropsychopharmacol C1 [Petryshen, T.; Blokland, G.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Petryshen, T.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X EI 1873-7862 J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2015 VL 25 SU 2 MA P.1.a.016 BP S167 EP S168 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CX2HR UT WOS:000365518200138 ER PT J AU Petryshen, TL Gjeluci, K Garza, J Leussis, M AF Petryshen, T. L. Gjeluci, K. Garza, J. Leussis, M. TI Genetic and pharmacological investigation of compulsive and impulsive behaviours SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 28th Congress of the European-College-of-Neuropsychopharmacology (ECNP) CY AUG 29-SEP 01, 2015 CL Amsterdam, NETHERLANDS SP European Coll Neuropsychopharmacol C1 [Petryshen, T. L.; Gjeluci, K.; Garza, J.; Leussis, M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X EI 1873-7862 J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2015 VL 25 SU 2 MA S.07.03 BP S120 EP S120 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CX2HR UT WOS:000365518200031 ER PT J AU Bortfeld, T Ramakrishnan, J Tsitsiklis, JN Unkelbach, J AF Bortfeld, Thomas Ramakrishnan, Jagdish Tsitsiklis, John N. Unkelbach, Jan TI Optimization of Radiation Therapy Fractionation Schedules in the Presence of Tumor Repopulation SO INFORMS JOURNAL ON COMPUTING LA English DT Article DE dynamic programming: applications; healthcare: treatment ID LINEAR-QUADRATIC MODEL; ADAPTIVE FRACTIONATION; DOSE DISTRIBUTION; CLINICAL-DATA; RADIOTHERAPY; CANCER; GROWTH; PROBABILITY; IRRADIATION; CELLS AB We analyze the effect of tumor repopulation on optimal dose delivery in radiation therapy. We are primarily motivated by accelerated tumor repopulation toward the end of radiation treatment, which is believed to play a role in treatment failure for some tumor sites. A dynamic programming framework is developed to determine an optimal fractionation scheme based on a model of cell kill from radiation and tumor growth in between treatment days. We find that faster tumor growth suggests shorter overall treatment duration. In addition, the presence of accelerated repopulation suggests larger dose fractions later in the treatment to compensate for the increased tumor proliferation. We prove that the optimal dose fractions are increasing over time. Numerical simulations indicate a potential for improvement in treatment effectiveness. C1 [Bortfeld, Thomas; Unkelbach, Jan] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Bortfeld, Thomas; Unkelbach, Jan] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Ramakrishnan, Jagdish] Univ Wisconsin, Wisconsin Inst Discovery, Madison, WI 53715 USA. [Tsitsiklis, John N.] MIT, Lab Informat & Decis Syst, Cambridge, MA 02139 USA. RP Bortfeld, T (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM tbortfeld@partners.org; jramakrishn2@wisc.edu; jnt@mit.edu; junkelbach@partners.org FU Siemens FX The authors thank David Craft and Ehsan Salari for helpful discussions and feedback. Thanks to anonymous reviewers for pointing out a generalization of Corollary 1 and also for very helpful feedback that has improved this paper. This research was partially funded by Siemens and was performed while the second author was with the Laboratory for Information and Decision Systems, Massachusetts Institute of Technology. NR 64 TC 1 Z9 1 U1 2 U2 4 PU INFORMS PI CATONSVILLE PA 5521 RESEARCH PARK DR, SUITE 200, CATONSVILLE, MD 21228 USA SN 1091-9856 EI 1526-5528 J9 INFORMS J COMPUT JI INFORMS J. Comput. PD FAL PY 2015 VL 27 IS 4 BP 788 EP 803 DI 10.1287/ijoc.2015.0659 PG 16 WC Computer Science, Interdisciplinary Applications; Operations Research & Management Science SC Computer Science; Operations Research & Management Science GA CX9WT UT WOS:000366057400013 ER PT J AU Oldenburg, O Teerlink, JR AF Oldenburg, Olaf Teerlink, John R. TI Screening for Sleep-Disordered Breathing in Patients Hospitalized for Heart Failure SO JACC-HEART FAILURE LA English DT Editorial Material DE acute decompensated heart failure; hospitalized patients; oxygen desaturation index; plethysmography; sleep-disordered breathing ID PROGNOSTIC IMPACT; APNEA; PREVALENCE C1 [Oldenburg, Olaf] Ruhr Univ Bochum, Dept Cardiol, Heart & Diabet Ctr North Rhine Westphalia, D-32545 Bad Oeynhausen, Germany. [Teerlink, John R.] San Francisco VA Med Ctr, Sect Cardiol, San Francisco, CA USA. [Teerlink, John R.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. RP Oldenburg, O (reprint author), Ruhr Univ Bochum, Dept Cardiol, Heart & Diabet Ctr North Rhine Westphalia, Univ Hosp, Georgstr 11, D-32545 Bad Oeynhausen, Germany. EM akleemeyer@hdz-nrw.de NR 14 TC 1 Z9 1 U1 0 U2 1 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 SEP PY 2015 VL 3 IS 9 BP 732 EP 733 DI 10.1016/j.jchf.2015.07.006 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CX4FU UT WOS:000365655300013 PM 26362450 ER PT J AU Wang, EH Corso, CD Rutter, CE Park, HS Chen, AB Kim, AW Wilson, LD Decker, RH Yu, JB AF Wang, Elyn H. Corso, Christopher D. Rutter, Charles E. Park, Henry S. Chen, Aileen B. Kim, Anthony W. Wilson, Lynn D. Decker, Roy H. Yu, James Byunghoon TI Postoperative Radiation Therapy Is Associated With Improved Overall Survival in Incompletely Resected Stage II and III Non-Small-Cell Lung Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MICROSCOPIC RESIDUAL DISEASE; DATA-BASE; RADIOTHERAPY; IMPACT; CARCINOMA; DATABASE; GROWTH AB Purpose To review trends in the use of postoperative radiotherapy (PORT) for stage II and III incompletely resected non-small-cell lung cancer (NSCLC) and evaluate the association between PORT and survival in such patients. Patients and Methods We identified patients with pathologic stage N0-2, overall American Joint Committee on Cancer stage II or III NSCLC within the National Cancer Data Base who had undergone a lobectomy or pneumonectomy with positive surgical margins. Only patients coded as receiving external-beam PORT at 50 to 74 Gy or observation were included. To account for perioperative mortality, we excluded patients who survived less than 4 months after diagnosis. Multivariable logistic regression was used to determine factors associated with PORT receipt. Cox proportional hazards regression was performed for multivariable analyses of overall survival. Results Among 3,395 included patients, 1,207 (35.6%) received PORT. Predictors for the use of PORT among this patient population included age less than 60 years, treatment in a nonacademic facility, earlier year of diagnosis, decreased travel distance, lower nodal stage, and chemotherapy receipt. On multivariable analysis adjusting for demographic and clinicopathologic covariates, PORT (hazard ratio, 0.80; 95% CI, 0.70 to 092) was associated with improved survival. Subset analysis by nodal stage showed that PORT improved survival across all nodal stages. Conclusion PORT is associated with improved overall survival in patients with incompletely resected stage II or III N0-2 NSCLC. The use of PORT for this population in more recent years has been declining. In the absence of randomized trials evaluating PORT utilization for this patient population, our findings strongly support the delivery of PORT in patients with incompletely resected NSCLC. (C) 2015 by American Society of Clinical Oncology C1 [Wang, Elyn H.; Corso, Christopher D.; Rutter, Charles E.; Park, Henry S.; Kim, Anthony W.; Wilson, Lynn D.; Decker, Roy H.; Yu, James Byunghoon] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Rutter, Charles E.; Park, Henry S.; Kim, Anthony W.; Decker, Roy H.; Yu, James Byunghoon] Canc Outcomes Publ Policy & Effectiveness Res Ctr, New Haven, CT USA. [Chen, Aileen B.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Chen, Aileen B.] Harvard Univ, Sch Med, Boston, MA USA. RP Yu, JB (reprint author), Yale Univ, Sch Med, Therapeut Radiol, HRT 138,333 Cedar St, New Haven, CT 06520 USA. EM james.b.yu@yale.edu OI Park, Henry/0000-0002-9366-8514 FU Merck; 21st Century Oncology; 21st Century Oncology (Inst) FX Merck; Merck, 21st Century Oncology; 21st Century Oncology (Inst) NR 24 TC 11 Z9 12 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 SEP 1 PY 2015 VL 33 IS 25 BP 2727 EP U25 DI 10.1200/JCO.2015.61.1517 PG 10 WC Oncology SC Oncology GA CX4ST UT WOS:000365691300006 PM 26101240 ER PT J AU May, P Garrido, MM Cassel, JB Kelley, AS Meier, DE Normand, C Smith, TJ Stefanis, L Morrison, RS AF May, Peter Garrido, Melissa M. Cassel, J. Brian Kelley, Amy S. Meier, Diane E. Normand, Charles Smith, Thomas J. Stefanis, Lee Morrison, R. Sean TI Prospective Cohort Study of Hospital Palliative Care Teams for Inpatients With Advanced Cancer: Earlier Consultation Is Associated With Larger Cost-Saving Effect SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LENGTH-OF-STAY; PROPENSITY SCORES; IMPACT; MEDICINE; ONCOLOGY; HEALTH AB Purpose Previous studies report that early palliative care is associated with clinical benefits, but there is limited evidence on economic impact. This article addresses the research question: Does timing of palliative care have an impact on its effect on cost? Patients and Methods Using a prospective, observational design, clinical and cost data were collected for adult patients with an advanced cancer diagnosis admitted to five US hospitals from 2007 to 2011. The sample for economic evaluation was 969 patients; 256 were seen by a palliative care consultation team, and 713 received usual care only. Subsamples were created according to time to consult after admission. Propensity score weights were calculated, matching the treatment and comparison arms specific to each subsample on observed confounders. Generalized linear models with a distribution and a log link were applied to estimate the mean treatment effect on cost within subsamples. Results Earlier consultation is associated with a larger effect on total direct cost. Intervention within 6 days is estimated to reduce costs by -$1,312 (95% CI, -$2,568 to -$56; P = .04) compared with no intervention and intervention within 2 days by -$2,280 (95% CI, -$3,438 to -$1,122; P < .001); these reductions are equivalent to a 14% and a 24% reduction, respectively, in cost of hospital stay. Conclusion Earlier palliative care consultation during hospital admission is associated with lower cost of hospital stay for patients admitted with an advanced cancer diagnosis. These findings are consistent with a growing body of research on quality and survival suggesting that early palliative care should be more widely implemented. (C) 2015 by American Society of Clinical Oncology C1 [May, Peter; Normand, Charles] Univ Dublin Trinity Coll, Ctr Hlth Policy & Management, Dublin 2, Ireland. [May, Peter; Garrido, Melissa M.; Kelley, Amy S.; Meier, Diane E.; Stefanis, Lee; Morrison, R. Sean] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Garrido, Melissa M.; Stefanis, Lee; Morrison, R. Sean] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Cassel, J. Brian] Virginia Commonwealth Univ, Richmond, VA USA. [Smith, Thomas J.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. RP May, P (reprint author), Univ Dublin Trinity Coll, Ctr Hlth Policy & Management, 3-4 Foster Pl, Dublin 2, Ireland. EM mayp2@tcd.ie RI May, Peter/B-2107-2017; OI May, Peter/0000-0001-8501-6500; Normand, Charles/0000-0002-0885-5754 FU National Cancer Institute (NCI); National Institute of Nursing Research in the United States; Health Research Board (Ireland); NCI [P30 CA 006973]; Veterans Affairs Health Services Research and Development career development award [CDA 11-201/CDP 12-255]; Midcareer Investigator Award in Patient-Oriented Research [5K24AG022345]; Claude D. Pepper Older Americans Independence Center at the Icahn School of Medicine at Mount Sinai [5P30AG028741]; National Palliative Care Research Center; National Institute on Aging [1K23AG040774-01A1] FX Supported by the National Cancer Institute (NCI) and the National Institute of Nursing Research in the United States. P.M. is sponsored by a health economics fellowship from the Health Research Board (Ireland) and NCI. M.M.G. is supported by a Veterans Affairs Health Services Research and Development career development award (CDA 11-201/CDP 12-255). T.J.S. is supported by NCI Grant No. P30 CA 006973 to Sidney Kimmel Comprehensive Cancer Center. R.S.M. was the recipient of a Midcareer Investigator Award in Patient-Oriented Research (5K24AG022345) during the course of this work. This work was supported by the National Institute on Aging, Claude D. Pepper Older Americans Independence Center at the Icahn School of Medicine at Mount Sinai (Grant No. 5P30AG028741), and the National Palliative Care Research Center. A.S.K. time was funded by the National Institute on Aging (Grant No. 1K23AG040774-01A1). NR 39 TC 26 Z9 26 U1 4 U2 5 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 SEP 1 PY 2015 VL 33 IS 25 BP 2745 EP U47 DI 10.1200/JCO.2014.60.2334 PG 10 WC Oncology SC Oncology GA CX4ST UT WOS:000365691300008 PM 26056178 ER PT J AU Metzger, O Giobbie-Hurder, A Mallon, E Gusterson, B Viale, G Winer, EP Thurlimann, B Gelber, RD Colleoni, M Ejlertsen, B Debled, M Price, KN Regan, MM Coates, AS Goldhirsch, A AF Metzger Filho, Otto Giobbie-Hurder, Anita Mallon, Elizabeth Gusterson, Barry Viale, Giuseppe Winer, Eric P. Thuerlimann, Beat Gelber, Richard D. Colleoni, Marco Ejlertsen, Bent Debled, Marc Price, Karen N. Regan, Meredith M. Coates, Alan S. Goldhirsch, Aron TI Relative Effectiveness of Letrozole Compared With Tamoxifen for Patients With Lobular Carcinoma in the BIG 1-98 Trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID EARLY BREAST-CANCER; ADJUVANT ENDOCRINE THERAPY; INTERNATIONAL EXPERT CONSENSUS; POSTMENOPAUSAL WOMEN; NEOADJUVANT CHEMOTHERAPY; PREOPERATIVE CHEMOTHERAPY; AROMATASE INHIBITORS; RANDOMIZED-TRIAL; PREDICTIVE-VALUE; DOUBLE-BLIND AB Purpose To evaluate the relative effectiveness of letrozole compared with tamoxifen for patients with invasive ductal or lobular carcinoma. Patients and Methods Patients diagnosed with early-stage invasive ductal carcinoma (IDC) or classic invasive lobular carcinoma (ILC) who were randomly assigned onto the Breast International Group (BIG) 1-98 trial and who had centrally reviewed pathology data were included (N = 2,923). HER2-negative IDC and ILC were additionally classified as hormone receptor-positive with high (luminal B [LB] -like) or low (luminal A [LA] -like) proliferative activity by Ki-67 labeling index. Survival analyses were performed with weighted Cox models that used inverse probability of censoring weighted modeling. Results The median follow-up time was 8.1 years. In multivariable models for disease-free survival (DFS), significant interactions between treatment and histology (ILC or IDC; P = .006) and treatment and subgroup (LB like or LA like; P = .01) were observed. In the ILC subset, there was a 66% reduction in the hazard of a DFS event with letrozole for LB (hazard ratio [HR], 0.34; 95% CI, 0.21 to 0.55) and a 50% reduction for LA subtypes (HR, 0.50; 95% CI, 0.32 to 0.78). In the IDC subset, there was a significant 35% reduction in the hazard of a DFS event with letrozole for the LB subtype (HR, 0.65; 95% CI, 0.53 to 0.79), but no difference between treatments was noted for IDC and the LA subtype (HR, 0.95; 95% CI, 0.76 to 1.20). Conclusion The magnitude of benefit of adjuvant letrozole is greater for patients diagnosed with lobular carcinoma versus ductal carcinoma. (C) 2015 by American Society of Clinical Oncology C1 [Metzger Filho, Otto; Giobbie-Hurder, Anita; Winer, Eric P.] Dana Farber Canc Inst, Boston, MA USA. [Gelber, Richard D.; Regan, Meredith M.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Price, Karen N.] Frontier Sci & Technol Res, Boston, MA USA. [Gusterson, Barry] Univ Glasgow, Inst Canc Sci, Glasgow, Lanark, Scotland. [Viale, Giuseppe] Univ Milan, I-20122 Milan, Italy. [Colleoni, Marco; Goldhirsch, Aron] European Inst Oncol, Milan, Italy. [Thuerlimann, Beat] Kantonsspital, St Gallen, Switzerland. [Thuerlimann, Beat] Swiss Grp Clin Canc Res, Bern, Switzerland. [Ejlertsen, Bent] Rigshosp, DK-2100 Copenhagen, Denmark. [Debled, Marc] Inst Bergoniie, Bordeaux, France. [Coates, Alan S.] Int Breast Canc Study Grp, Bern, Switzerland. [Coates, Alan S.] Univ Sydney, Sydney, NSW 2006, Australia. RP Metzger, O (reprint author), 450 Brookline Ave,Yawkey 1238, Boston, MA 02215 USA. EM otto_metzger@dfci.harvard.edu FU Novartis [BIG 1-98]; Swedish Cancer Society; Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group; Frontier Science and Technology Research Foundation; Swiss Group for Clinical Cancer Research; US National Institute of Health [CA-75362]; Cancer Research Switzerland/Oncosuisse; Foundation for Clinical Cancer Research of Eastern Switzerland FX Supported by Novartis (sponsorship of the BIG 1-98 trial) and coordinated by the International Breast Cancer Study Group (IBCSG). The IBCSG was supported by the Swedish Cancer Society, the Cancer Council Australia, Australian New Zealand Breast Cancer Trials Group, Frontier Science and Technology Research Foundation, Swiss Group for Clinical Cancer Research, US National Institute of Health Grant No. CA-75362, Cancer Research Switzerland/Oncosuisse, and the Foundation for Clinical Cancer Research of Eastern Switzerland. NR 46 TC 5 Z9 5 U1 3 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2015 VL 33 IS 25 BP 2772 EP U85 DI 10.1200/JCO.2015.60.8133 PG 14 WC Oncology SC Oncology GA CX4ST UT WOS:000365691300011 PM 26215945 ER PT J AU Stenzinger, A Weichert, W Lennerz, JK Klauschen, F AF Stenzinger, Albrecht Weichert, Wilko Lennerz, Jochen K. Klauschen, Frederick TI Basket Trials: Just the End of the First Quarter SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID TARGETED THERAPY; CANCER C1 [Stenzinger, Albrecht] Univ Heidelberg Hosp, Heidelberg, Germany. [Stenzinger, Albrecht] Natl Ctr Tumor Dis, Heidelberg, Germany. [Weichert, Wilko] Univ Heidelberg Hosp, Natl Ctr Tumor Dis, Heidelberg, Germany. [Weichert, Wilko] German Canc Consortium, Heidelberg, Germany. [Lennerz, Jochen K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Klauschen, Frederick] Charite, Einstein Fdn, Berlin, Germany. RP Stenzinger, A (reprint author), Univ Heidelberg Hosp, Heidelberg, Germany. NR 10 TC 7 Z9 7 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 SEP 1 PY 2015 VL 33 IS 25 BP 2823 EP U145 DI 10.1200/JCO.2015.62.1516 PG 3 WC Oncology SC Oncology GA CX4ST UT WOS:000365691300019 PM 26169614 ER PT J AU Bekelman, JE Mitra, N Handorf, EA Uzzo, RG Hahn, SM Polsky, D Armstrong, K AF Bekelman, Justin E. Mitra, Nandita Handorf, Elizabeth A. Uzzo, Robert G. Hahn, Stephen M. Polsky, Daniel Armstrong, Katrina TI Older Men With Locally Advanced Prostate Cancer: To Treat or Not to Treat? Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 [Bekelman, Justin E.; Mitra, Nandita; Polsky, Daniel] Univ Penn, Philadelphia, PA 19104 USA. [Handorf, Elizabeth A.; Uzzo, Robert G.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Hahn, Stephen M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Armstrong, Katrina] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bekelman, JE (reprint author), Univ Penn, Philadelphia, PA 19104 USA. NR 4 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 SEP 1 PY 2015 VL 33 IS 25 BP 2833 EP U165 DI 10.1200/JCO.2015.62.4643 PG 2 WC Oncology SC Oncology GA CX4ST UT WOS:000365691300029 PM 26215947 ER PT J AU Ellison, RT Barysauskas, CM Rundensteiner, EA Wang, D Barton, B AF Ellison, Richard T., III Barysauskas, Constance M. Rundensteiner, Elke A. Wang, Di Barton, Bruce TI A Prospective Controlled Trial of an Electronic Hand Hygiene Reminder System SO OPEN FORUM INFECTIOUS DISEASES LA English DT Article DE electronic monitoring; hand hygiene; intensive care unit; prospective controlled trial ID HEALTH-CARE WORKERS; AUTOMATED MONITORING-SYSTEM; REAL-TIME FEEDBACK; UNIT; TECHNOLOGY; GUIDELINES; TRANSMISSION AB Background. The use of electronic hand hygiene reminder systems has been proposed as an approach to improve hand hygiene compliance among healthcare workers, although information on efficacy is limited. We prospectively assessed whether hand hygiene activities among healthcare workers could be increased using an electronic hand hygiene monitoring and reminder system. Methods. A prospective controlled clinical trial was conducted in 2 medical intensive care units (ICUs) at an academic medical center with comparable patient populations, healthcare staff, and physical layout. Hand hygiene activity was monitored concurrently in both ICUs, and the reminder system was installed in the test ICU. The reminder system was tested during 3 administered phases including: room entry/exit chimes, display of real-time hand hygiene activity, and a combination of the 2. Results. In the test ICU, the mean number of hand hygiene events increased from 1538 per day at baseline to 1911 per day (24% increase) with the use of a combination of room entry/exit chimes, real-time displays of hand hygiene activity, and manager reports (P < .001); in addition, the ratio of hand hygiene to room entry/exit events also increased from 26.1% to 36.6% (40% increase, P < .001). The performance returned to baseline (1473 hand hygiene events per day) during the follow-up phase. There was no significant change in hand hygiene activity in the control ICU during the course of the trial. Conclusions. In an ICU setting, an electronic hand hygiene reminder system that provided real-time feedback on overall unit-wide hand hygiene performance significantly increased hand hygiene activity. C1 [Ellison, Richard T., III] Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, Dept Med, Worcester, MA 01655 USA. [Barysauskas, Constance M.; Barton, Bruce] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA 01655 USA. [Barysauskas, Constance M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Rundensteiner, Elke A.; Wang, Di] Worcester Polytech Inst, Dept Comp Sci, Worcester, MA USA. [Wang, Di] Microsoft Corp, Redmond, WA 98052 USA. RP Ellison, RT (reprint author), Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, 55 Lake Ave North, Worcester, MA 01655 USA. EM richard.ellison@umassmemorial.org NR 36 TC 1 Z9 1 U1 1 U2 2 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 FAL PY 2015 VL 2 IS 4 DI 10.1093/ofid/ofv121 PG 8 WC Infectious Diseases SC Infectious Diseases GA CX6BY UT WOS:000365787400009 ER PT J AU Fields, EC Kuperberg, GR AF Fields, Eric C. Kuperberg, Gina R. TI Loving yourself more than your neighbor: ERPs reveal online effects of a self-positivity bias SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE event-related potentials (ERP); N400; self; emotion; positive illusions ID EVENT-RELATED POTENTIALS; SPONTANEOUS TRAIT INFERENCE; SEMANTIC INTEGRATION; DISCOURSE; IMPLICIT; BRAIN; EMOTION; ESTEEM; COMPREHENSION; CONCRETENESS AB A large body of social psychological research suggests that we think quite positively of ourselves, often unrealistically so. Research on this 'self-positivity bias' has relied mainly on self-report and behavioral measures, but these can suffer from a number of problems including confounds that arise from the desire to present oneself well. What has not been clearly assessed is whether the self-positivity bias influences the processing of incoming information as it unfolds in real time. In this study, we used event-related potentials to address this question. Participants read two-sentence social vignettes that were either self-or other-relevant. Pleasant words in self-relevant contexts evoked a smaller negativity between 300 and 500 ms (the N400 time window) than the same words in other-relevant contexts, suggesting that comprehenders were more likely to expect positive information when a scenario referred to themselves. This finding indicates that the self-positivity bias is available online, acting as a general schema that directly influences real-time comprehension. C1 [Fields, Eric C.; Kuperberg, Gina R.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Fields, Eric C.; Kuperberg, Gina R.] MGH HST Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Kuperberg, Gina R.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. RP Fields, EC (reprint author), Tufts Univ, Dept Psychol, 490 Boston Ave, Medford, MA 02155 USA. EM eric.fields@tufts.edu FU NIMH [R01 MH071635]; NARSAD; Tufts University; Sidney Baer Trust FX This work was supported by NIMH (R01 MH071635) and NARSAD (with the Sidney Baer Trust) grants, as well as a Senior Faculty Research Award from Tufts University to Gina Kuperberg. We thank Camila Carneiro de Lima, Rohan Natraj and Erich Tusch for help with data collection and other aspects of the study. We also thank Heather Urry, Phil Holcomb, Allison Fogel and three anonymous reviewers for comments on the manuscript. NR 64 TC 5 Z9 5 U1 4 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1749-5016 EI 1749-5024 J9 SOC COGN AFFECT NEUR JI Soc. Cogn. Affect. Neurosci. PD SEP PY 2015 VL 10 IS 9 BP 1202 EP 1209 DI 10.1093/scan/nsv004 PG 8 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA CX2QJ UT WOS:000365541400006 PM 25605967 ER PT J AU Touroutoglou, A Lindquist, KA Dickerson, BC Barrett, LF AF Touroutoglou, Alexandra Lindquist, Kristen A. Dickerson, Bradford C. Barrett, Lisa Feldman TI Intrinsic connectivity in the human brain does not reveal networks for 'basic' emotions SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE emotions; intrinsic functional connectivity networks; basic emotion theory; conceptual act theory of emotion ID LARGE-SCALE BRAIN; BILATERAL AMYGDALA DAMAGE; FUNCTIONAL CONNECTIVITY; RESTING-STATE; ANTERIOR INSULA; ARCHITECTURE; SYSTEM; METAANALYSIS; FEAR; MIND AB We tested two competing models for the brain basis of emotion, the basic emotion theory and the conceptual act theory of emotion, using resting-state functional connectivity magnetic resonance imaging (rs-fcMRI). The basic emotion view hypothesizes that anger, sadness, fear, disgust and happiness each arise from a brain network that is innate, anatomically constrained and homologous in other animals. The conceptual act theory of emotion hypothesizes that an instance of emotion is a brain state constructed from the interaction of domain-general, core systems within the brain such as the salience, default mode and frontoparietal control networks. Using peak coordinates derived from a meta-analysis of task-evoked emotion fMRI studies, we generated a set of whole-brain rs-fcMRI 'discovery' maps for each emotion category and examined the spatial overlap in their conjunctions. Instead of discovering a specific network for each emotion category, variance in the discovery maps was accounted for by the known domain-general network. Furthermore, the salience network is observed as part of every emotion category. These results indicate that specific networks for each emotion do not exist within the intrinsic architecture of the human brain and instead support the conceptual act theory of emotion. C1 [Touroutoglou, Alexandra] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Touroutoglou, Alexandra; Dickerson, Bradford C.; Barrett, Lisa Feldman] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Touroutoglou, Alexandra; Barrett, Lisa Feldman] Massachusetts Gen Hosp, Dept Psychiat, Div Psychiat Neuroimaging, Charlestown, MA USA. [Touroutoglou, Alexandra; Dickerson, Bradford C.; Barrett, Lisa Feldman] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Lindquist, Kristen A.] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA. [Lindquist, Kristen A.] Univ N Carolina, Biomed Res Imaging Ctr, Chapel Hill, NC USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Frontotemporal Disorders Unit, Charlestown, MA USA. [Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. RP Touroutoglou, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Sch Med, Bldg 149,13th St,Suite 2691, Charlestown, MA 02129 USA. EM atourout@nmr.mgh.harvard.edu FU National Institutes of Health [DP1OD003312]; National Institute on Aging [R01 AG030311-06A1]; National Center For Research Resources [1S10RR023401, 1S10RR019307, 1S10RR023043]; Harvard University Mind/Brain/Behavior Initiative FX We thank Mark Hollenbeck for his help with data analysis and construction of the figures and Randy L. Buckner for providing the data used in the analysis of Samples 1 and 2 and the preprocessing/rs-fcMRI tools. This work was supported by the National Institutes of Health Director's Pioneer Award (DP1OD003312) to L.F.B., a National Institute on Aging grant (R01 AG030311-06A1) to L.F.B., and B.C.D., the Shared Instrumentation Grants (1S10RR023401, 1S10RR019307 and 1S10RR023043) from the National Center For Research Resources, and a Harvard University Mind/Brain/Behavior Initiative Postdoctoral Fellowship to K.A.L. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources, the National Institutes of Health or the National Institute on Aging. NR 83 TC 12 Z9 13 U1 6 U2 19 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1749-5016 EI 1749-5024 J9 SOC COGN AFFECT NEUR JI Soc. Cogn. Affect. Neurosci. PD SEP PY 2015 VL 10 IS 9 BP 1257 EP 1265 DI 10.1093/scan/nsv013 PG 9 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA CX2QJ UT WOS:000365541400013 PM 25680990 ER PT J AU Finch, SA Wasserman, R Nabi-Burza, E Hipple, B Oldendick, R Winickoff, JP AF Finch, Stacia A. Wasserman, Richard Nabi-Burza, Emara Hipple, Bethany Oldendick, Robert Winickoff, Jonathan P. TI Overcoming Challenges in the Changing Environment of Practice-Based Research SO ANNALS OF FAMILY MEDICINE LA English DT Article DE methodology; secondhand smoke; practice-based research; trial design; follow-up; response rate; pediatrics; primary care; communication ID SMOKING; PARENTS; SETTINGS; NETWORK; HEALTH; TRIAL AB PURPOSE Conducting studies in national practice-based research networks presents logistic and methodologic challenges. Pediatric Research in Office Settings (PROS) has learned valuable lessons in implementing new strategies and adapting to challenges. We describe practical challenges and results of novel applied strategies in implementing and testing the Clinical Effort Against Secondhand Smoke Exposure (CEASE) intervention as part of a national-level cluster-randomized controlled trial. METHODS In the trial, 20 PROS practices were randomized to either a CEASE intervention arm or a control arm. Parents of children seen in the office who indicated smoking in the past 7 days were asked to complete a postvisit enrollment interview and telephone interviews 3 and 12 months later. Identified challenges included (1) recruiting 20 practices serving a high percentage of parent smokers; (2) screening all parents bringing children for visits and enrolling eligible parents who smoked; and (3) achieving an acceptable 12-month telephone response rate. RESULTS A total of 47 interested practices completed the Practice Population Survey, of which 20 practices in 16 states completed parent enrollment. Thirty-two research assistants screened 18,607 parents and enrolled 1,980 of them. The initial telephone interview response rate was 56% at 12 months, with incorrect and disconnected numbers accounting for nearly 60% of nonresponses. The response rate rose to 67% after practices supplied 532 new contact numbers and 754 text messages were sent, with 389 parents completing interviews. CONCLUSION The strategies we used to overcome methodologic barriers in conducting a national intervention trial allowed data collection to be completed in the office setting and increased the telephone interview response rate. C1 [Finch, Stacia A.; Wasserman, Richard] Amer Acad Pediat, Pediat Res Off Settings, Elk Grove Village, IL USA. [Wasserman, Richard] Univ Vermont, Dept Pediat, Burlington, VT USA. [Nabi-Burza, Emara; Hipple, Bethany; Winickoff, Jonathan P.] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth & Res Policy, Boston, MA 02114 USA. [Nabi-Burza, Emara; Hipple, Bethany; Winickoff, Jonathan P.] Amer Acad Pediat, Julius B Richmond Ctr Excellence, Elk Grove Village, IL USA. [Oldendick, Robert] Univ S Carolina, Inst Publ Serv & Policy Res, Columbia, SC 29208 USA. RP Winickoff, JP (reprint author), Div Gen Pediat, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM Jwinickoff@mgh.harvard.edu FU National Institutes of Health NCI grant [R01-CA127127]; National Institute on Drug Abuse; Agency for Healthcare Research and Quality; Flight Attendant Medical Research Institute; HRSA MCHB [HRSA 5-UA6-10-001]; AAP FX This study was supported by the National Institutes of Health NCI grant R01-CA127127 (to Dr. Winickoff), the National Institute on Drug Abuse, and the Agency for Healthcare Research and Quality. This study was also partially supported by a grant from the Flight Attendant Medical Research Institute to the AAP Julius B. Richmond Center, and the Pediatric Research in Office Settings (PROS) Network receives core funding from the HRSA MCHB (HRSA 5-UA6-10-001) and the AAP. NR 19 TC 1 Z9 1 U1 1 U2 3 PU ANNALS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, LEAWOOD, KS 66211-2672 USA SN 1544-1709 EI 1544-1717 J9 ANN FAM MED JI Ann. Fam. Med. PD SEP-OCT PY 2015 VL 13 IS 5 BP 475 EP 479 DI 10.1370/afm.1809 PG 5 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA CW2RI UT WOS:000364839700014 PM 26371270 ER PT J AU Kekre, N Kim, HT Thanarajasingam, G Armand, P Antin, JH Cutler, C Nikiforow, S Ho, VT Koreth, J Alyea, EP Soiffer, RJ AF Kekre, Natasha Kim, Haesook T. Thanarajasingam, Gita Armand, Philippe Antin, Joseph H. Cutler, Corey Nikiforow, Sarah Ho, Vincent T. Koreth, John Alyea, Edwin P. Soiffer, Robert J. TI Efficacy of immune suppression tapering in treating relapse after reduced intensity allogeneic stem cell transplantation SO HAEMATOLOGICA LA English DT Article ID DONOR LYMPHOCYTE INFUSIONS; HEMATOLOGIC MALIGNANCIES AB For patients who relapse after allogeneic hematopoietic stem cell transplantation while still on immune suppression, there is anecdotal evidence that tapering the immune suppression may result in graft-versus-tumor activity. We reviewed the medical records of all patients with documented histological or radiographic disease recurrence within 1 year of stem cell transplantation while on immune suppression at our institution. The median time to relapse was 110 days (range, 18-311) after transplant. Among 123 patients with relapse treated with immune suppression tapering without chemotherapy, radiation, or donor lymphocyte infusion, 34 responded (33/101 reduced intensity conditioning transplant and 1/22 myeloablative conditioning transplant, 32.7% and 4.5% respectively; P=0.007). The median time to response after initiation of immune suppression tapering was 82 days (range, 16-189). Thirty-three patients (97.1%) had development or progression of acute or chronic graft-versus-host disease as a consequence of immune suppression tapering, at a median time of 39 days (range, 1698). Six patients subsequently relapsed late after initial response to immune suppression tapering at a median time of 2 years (range, 0.9-3.8). The median overall survival from immune suppression tapering for responders was 5.1 years (range, 1.9-not estimable). When clinically feasible, immune suppression tapering alone in patients who relapse early after reduced intensity conditioning allogeneic stem cell transplantation can produce durable remissions, but is almost always associated with graft-versus-host disease. C1 [Kekre, Natasha] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Kim, Haesook T.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Thanarajasingam, Gita] Mayo Clin, Div Hematol, Rochester, MN USA. [Armand, Philippe; Antin, Joseph H.; Cutler, Corey; Nikiforow, Sarah; Ho, Vincent T.; Koreth, John; Alyea, Edwin P.; Soiffer, Robert J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Soiffer, RJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA. EM rsoiffer@partners.org FU Jock and Bunny Adams Research and Education Endowment; Ted and Eileen Pasquarello Research Fund FX This work was supported by the Jock and Bunny Adams Research and Education Endowment and the Ted and Eileen Pasquarello Research Fund. NR 12 TC 0 Z9 0 U1 0 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD SEP PY 2015 VL 100 IS 9 BP 1222 EP 1227 DI 10.3324/haematol.2015.129650 PG 6 WC Hematology SC Hematology GA CW6BH UT WOS:000365081500033 PM 26088931 ER PT J AU Chambers, KJ Horstkotte, KA Shanley, K Lindsay, RW AF Chambers, Kyle J. Horstkotte, Kate A. Shanley, Kerry Lindsay, Robin W. TI Evaluation of Improvement in Nasal Obstruction Following Nasal Valve Correction in Patients With a History of Failed Septoplasty SO JAMA FACIAL PLASTIC SURGERY LA English DT Article ID QUALITY-OF-LIFE; FUNCTIONAL RHINOPLASTY; REVISION SEPTOPLASTY; OUTCOMES; SURGERY AB IMPORTANCE Patients with a septal deviation and concerns about nasal obstruction often undergo septoplasty to improve nasal airflow. Following primary septoplasty, however, some patients have persistent symptoms due to nasal valve dysfunction and may require nasal valve surgery. OBJECTIVES To evaluate the change in disease-specific quality of life for patients who undergo nasal valve correction after failed septoplasty using the Nasal Obstruction Symptom Evaluation (NOSE) survey and to determine whether identifiable anatomical risk factors are more common in patients with a history of failed septoplasty. DESIGN, SETTING, AND PARTICIPANTS Prospective observational outcomes study conducted at a tertiary care medical center. Forty patients who underwent nasal valve correction through an open approach from January 1, 2012, through December 31, 2014, with a history of septoplasty for nasal obstruction were included. Data analysis was conducted from January 1, 2013, through May 1, 2015. INTERVENTIONS Demographic information, a standardized nasal examination, and preoperative and postoperative NOSE scores were collected and reviewed. MAIN OUTCOMES AND MEASURES Comparison between preoperative and postoperative NOSE scores at 2, 4, and more than 6 months after surgery. RESULTS Forty patients were included in the study; 23 (57%) were male and 17 (43%) were female. The mean age was 39.3 years. Findings from preoperative nasal examination demonstrated moderate or severe internal nasal valve narrowing in 38 (95%) patients, internal nasal valve collapse in 19 (48%), external nasal valve narrowing in 18 (45%), or external nasal valve collapse in 16 (40%). The most common anatomical cause of obstruction was internal nasal valve narrowing in 38 (95%) patients, dorsal septum deflection in 26 (65%), and narrowed middle vault in 16 (40%). The mean (SD) preoperative NOSE score was 75.7 (20.1). Mean (SD) postoperative NOSE scores at 2, 4, and greater than 6 months were 31.4 (27.2), 34.0 (19.8), and 22.1 (18.8), respectively, with significantly improved NOSE scores at each time point compared with before surgery (P < .001). CONCLUSIONS AND RELEVANCE Nasal valve dysfunction remains an underdiagnosed entity and should be considered in all patients with septal deviation before septoplasty, especially in patients with a severe dorsal deflection and a narrow middle vault. In this study, surgical nasal valve correction demonstrated a significant reduction in nasal obstruction, as measured by a validated outcome measure, in patients for whom a previous septoplasty had failed. C1 [Chambers, Kyle J.; Horstkotte, Kate A.; Shanley, Kerry; Lindsay, Robin W.] Massachusetts Eye & Ear Infirm, Dept Otorhinolaryngol Head & Neck Surg, Boston, MA 62501 USA. [Chambers, Kyle J.; Horstkotte, Kate A.; Shanley, Kerry; Lindsay, Robin W.] Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02115 USA. RP Chambers, KJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otorhinolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 62501 USA. EM kyle_chambers@meei.harvard.edu NR 16 TC 6 Z9 6 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6076 EI 2168-6092 J9 JAMA FACIAL PLAST SU JI JAMA Facial Plast. Surg. PD SEP-OCT PY 2015 VL 17 IS 5 BP 347 EP 350 DI 10.1001/jamafacial.2015.0978 PG 4 WC Surgery SC Surgery GA CW6QX UT WOS:000365123600006 PM 26291169 ER PT J AU Shnayder, Y Lin, D Desai, SC Nussenbaum, B Sand, JP Wax, MK AF Shnayder, Yelizaveta Lin, Derrick Desai, Shaun C. Nussenbaum, Brian Sand, Jordan P. Wax, Mark K. TI Reconstruction of the Lateral Mandibular Defect A Review and Treatment Algorithm SO JAMA FACIAL PLASTIC SURGERY LA English DT Review ID FREE-FLAP RECONSTRUCTION; MAGNETIC-RESONANCE ANGIOGRAPHY; OSSEOUS FREE FLAPS; SOFT-TISSUE; OROMANDIBULAR RECONSTRUCTION; RADIAL FOREARM; THORACODORSAL ARTERY; OSTEOCUTANEOUS FLAP; ANGULAR BRANCH; ILIAC CREST AB Reconstruction of the lateral mandibular defect presents a complex challenge to the reconstructive surgeon, often involving interconnected soft-tissue and bone requirements. This review examines the current literature on functional outcomes of lateral mandibular reconstruction and presents an algorithm on selecting an optimal reconstructive choice for patients with lateral mandibular defects resulting from oncologic ablative surgery or trauma. PubMed and Medline searches on reconstructing lateral mandibular defect were performed of the English literature. Search terms included lateral mandibular defect, outcomes of mandibular reconstruction, and free flap reconstruction of mandible. Although most of the articles presented are retrospective reviews, priority was given to the articles with high-quality level of evidence. Restoration of function, including speech and swallow, and acceptable cosmetic result are the primary objectives of lateral mandibular reconstruction. When reconstructing the mandible in a patient following tumor extirpation, the patient's overall prognosis, medical comorbidities, and need for adjuvant therapy should be considered. In the patient with aggressive malignant disease and a poor prognosis, a less complex reconstruction, such as soft-tissue flap with or without a reconstruction plate, may be adequate. In a dentate patient with favorable prognosis, a durable reconstruction, such as osseocutaneous microvascular free flap, is often preferred. Various reconstructive options are available for patients with lateral mandibular defects. Depending on the predominance of the soft-tissue or bony components of the defect, with consideration of the patient's characteristics and functional and aesthetic goals, the surgeon can wisely select from these reconstructive possibilities. C1 [Shnayder, Yelizaveta] Univ Kansas, Sch Med, Dept Otolaryngol Head & Neck Surg, Kansas City, KS 66160 USA. [Lin, Derrick] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Head & Neck Oncol, Boston, MA 02114 USA. [Desai, Shaun C.; Nussenbaum, Brian; Sand, Jordan P.] Washington Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, St Louis, MO 63110 USA. [Wax, Mark K.] Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Portland, OR USA. RP Shnayder, Y (reprint author), Univ Kansas, Sch Med, Dept Otolaryngol Head & Neck Surg, 3901 Rainbow Blvd, Kansas City, KS 66160 USA. EM yshnayder@kumc.edu NR 33 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6076 EI 2168-6092 J9 JAMA FACIAL PLAST SU JI JAMA Facial Plast. Surg. PD SEP-OCT PY 2015 VL 17 IS 5 BP 367 EP 373 DI 10.1001/jamafacial.2015.0825 PG 7 WC Surgery SC Surgery GA CW6QX UT WOS:000365123600011 PM 26204563 ER PT J AU Williams, GD AF Williams, Glynne D. TI Two Cases of Urinary Tract Infection Caused by Propionimicrobium lymphophilum SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID ANAEROBIC-BACTERIA AB The first case reports involving Propionimicrobium lymphophilum, a rarely encountered anaerobic Gram-positive non-sporeforming rod, are presented here as urinary tract infections. Initial detection of these bacteria required urine Gram stains. Comparison of the type strain to the two isolates by various methods is depicted and includes antimicrobial susceptibility data. C1 [Williams, Glynne D.] VA Cent Western Massachusetts Healthcare Syst, US Dept Vet Affairs, Pathol & Lab Med Serv, Leeds, MA 01053 USA. RP Williams, GD (reprint author), VA Cent Western Massachusetts Healthcare Syst, US Dept Vet Affairs, Pathol & Lab Med Serv, Leeds, MA 01053 USA. EM glynne.williams@va.gov NR 14 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 EI 1098-660X J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 2015 VL 53 IS 9 BP 3077 EP 3080 DI 10.1128/JCM.00438-15 PG 4 WC Microbiology SC Microbiology GA CW6TE UT WOS:000365129900046 PM 26135862 ER PT J AU Friedman, MJ AF Friedman, Matthew J. TI Improving Our Understanding of Posttraumatic Trajectories SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material ID VIETNAM C1 [Friedman, Matthew J.] US Dept Vet Affairs, White River Jct, VT USA. [Friedman, Matthew J.] Geisel Sch Med Dartmouth, Dept Psychiat & Pharmacol Toxicol, Hanover, NH USA. RP Friedman, MJ (reprint author), VA Med Ctr, Natl Ctr PTSD, 215 North Main St, White River Jct, VT 05009 USA. EM Matthew.Friedman@Dartmouth.edu NR 9 TC 0 Z9 0 U1 1 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 2015 VL 76 IS 9 BP E1153 EP E1154 DI 10.4088/JCP.14com09488 PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CX0UM UT WOS:000365412500019 PM 26455689 ER PT J AU Nierenberg, AA Sylvia, LG Ellard, KK Ghaznavi, S Deckersbach, T AF Nierenberg, Andrew A. Sylvia, Louisa G. Ellard, Kristen K. Ghaznavi, Sharmin Deckersbach, Thilo TI What Happens Now? The Importance of Naturalistic Course After First Mania SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material DE Bipolar Disorder ID TREATMENT ENHANCEMENT PROGRAM; SOCIAL RHYTHM THERAPY; BIPOLAR-I DISORDER; COMORBID ANXIETY; STEP-BD; TRIAL; OUTCOMES; PSYCHOEDUCATION; PSYCHOTHERAPY; INTERVENTION C1 [Nierenberg, Andrew A.; Sylvia, Louisa G.; Ellard, Kristen K.; Ghaznavi, Sharmin; Deckersbach, Thilo] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Nierenberg, Andrew A.; Sylvia, Louisa G.; Ghaznavi, Sharmin; Deckersbach, Thilo] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 50 Staniford St,5th Floor, Boston, MA 02114 USA. EM anierenberg@mgh.harvard.edu FU US Army DARPA SUBNETS [W911NF-14-2-0045]; US National Institute of Mental Health [5U01MH092221-02] FX Dr Ellard is supported by grant W911NF-14-2-0045 from US Army DARPA SUBNETS and grant 5U01MH092221-02 from the US National Institute of Mental Health. NR 26 TC 0 Z9 0 U1 1 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 2015 VL 76 IS 9 BP E1161 EP E1163 DI 10.4088/JCP.14com09596 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CX0UM UT WOS:000365412500023 PM 26455693 ER PT J AU de Andrade, LF AF de Andrade, Lucas Ferrari TI Methods to microscopically analyze melanoma tumors in mice SO JOURNAL OF HISTOTECHNOLOGY LA English DT Article DE Angiogenesis; Histology; Melanoma; Microscopy; Necrosis ID METASTATIC MELANOMA; MURINE MELANOMA; CELL-LINES; ANGIOGENESIS; MODEL AB Melanoma is a metastatic type of skin cancer that is difficult to treat and the majority of efforts are directed to the design of new drugs. Many experimental drugs have been designed, and basic research has been done in melanoma-bearing mice, but the studies in general were only based on macroscopic approaches, such as those to determine number and size of tumors. A microscopic view can reveal new details. In this study, B16F10 melanoma tumors were used in C57BL6 mice to develop subcutaneous and lungs metastases. The histology of subcutaneous tumors revealed areas of necrosis and angiogenesis. The sections from the lungs showed the metastatic tumors. Furthermore, by ImageJ's macro languages, an electronic and automated analysis was designed of tumor cell death, angiogenesis density, the metastatic tumor burden in the lungs, and the staining of different proteins by immunofluorescence was designed. Given these facts, the analysis significantly improved the evaluation of tumor burden in mice melanoma models. C1 [de Andrade, Lucas Ferrari] Univ Fed Parana, Dept Biol Celular, BR-81530900 Curitiba, PR, Brazil. [de Andrade, Lucas Ferrari] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA USA. RP de Andrade, LF (reprint author), Univ Fed Parana, Dept Biol Celular, Setor Ciencias Biol, Campus Ctr Politecn, BR-81530900 Curitiba, PR, Brazil. EM lferrarideandrade@gmail.com FU Fundacao Araucaria; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior FX Funding Fundacao Araucaria and Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior. NR 17 TC 0 Z9 0 U1 2 U2 5 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 0147-8885 EI 2046-0236 J9 J HISTOTECHNOL JI J. Histotechnol. PD SEP PY 2015 VL 38 IS 3 BP 75 EP 82 DI 10.1179/2046023615Y.0000000007 PG 8 WC Cell Biology SC Cell Biology GA CX0KO UT WOS:000365385500003 ER PT J AU Routhier, CA AF Routhier, Caitlin Ann TI Study in ER/PR and HER2 receptor IHC SO JOURNAL OF HISTOTECHNOLOGY LA English DT Article DE Histotechnology; Immunohistochemistry; Microscopy; Pathology AB Recently, the development of Estrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal Growth Factor Receptor 2 (HER2) receptors in immunohistochemistry has amassed significant prognostic value in the treatment of breast carcinomas. Its introduction provides an inexpensive and widely available testing protocol yielding vital pathological information regarding patient outcome and therapeutic response. However, in conjunction with its continued advancement, these markers withstand increased hindrance in reaching their full diagnostic potential due to the lack of a standardized protocol. The primary focus of this study was to develop standardized protocols for each breast marker. Through manipulation of antigen retrieval methods and dilutions, highly accurate and reproducible staining results were achieved. Validations of ER and PR were run with alternating Heat Induced Epitope Retrieval (HIER) methods using solutions buffered with EDTA and citrate. Simultaneous comparisons were run using the laboratory's Ventana platform, establishing parallels between previously validations and new optimizations to ease antibody transition. HER2 optimization initial workups included Dako, Thermo Fisher, and Ventana antibodies monitored over extended time periods. The finalized protocol utilizes Ventana's HER2 antibody validated to run on a Leica platform. The addition of an alternative hematoxylin counterstain and citric acid clarifier was applied in order to enhance staining clarity and ease of quantitation. The use of Ventana diluents in working antibody solution, restrictions on quantity made, and refrigeration, may create staining consistency. The laboratory used was able to offer a diagnostically significant receptor panel with minimal variations between cases, having an enormously positive impact on patient care. C1 [Routhier, Caitlin Ann] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Routhier, CA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM crouthier@partners.org NR 3 TC 0 Z9 0 U1 3 U2 3 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 0147-8885 EI 2046-0236 J9 J HISTOTECHNOL JI J. Histotechnol. PD SEP PY 2015 VL 38 IS 3 BP 91 EP 95 DI 10.1179/2046023615Y.0000000005 PG 5 WC Cell Biology SC Cell Biology GA CX0KO UT WOS:000365385500005 ER PT J AU Han, C Zhou, YB An, Q Li, F Li, DL Zhang, XJ Yu, ZJ Zheng, LL Duan, ZF Kan, QC AF Han, Chao Zhou, Yubing An, Qi Li, Feng Li, Duolu Zhang, Xiaojian Yu, Zujing Zheng, Lili Duan, Zhenfeng Kan, Quancheng TI MicroRNA-1 (miR-1) inhibits gastric cancer cell proliferation and migration by targeting MET SO TUMOR BIOLOGY LA English DT Article DE Gastric cancer; miR-1; Non-coding RNA; Tumor suppressor gene; Target therapy ID HEPATOCYTE GROWTH-FACTOR; C-MET; PROSTATE-CANCER; COLON-CANCER; LUNG-CANCER; TUMORIGENIC PROPERTIES; TUMOR-SUPPRESSOR; DOWN-REGULATION; A549 CELLS; EXPRESSION AB MicroRNAs (miRs) are short endogenous non-coding RNAs that act as posttranscriptional regulatory factors of gene expression. Downregulation of miR-1 has been reported in gastric cancer; however, the mechanisms underlying its functions via target genes in gastric cancer remain largely unknown. The purpose of this study was to investigate the mechanism by which miR-1 inhibits gastric cancer cell proliferation and migration. The effects of miR-1 on gastric cancer cell proliferation and migration were determined by MTT and wound-healing assays. Cell protein expression of the miR-1 target gene MET was analyzed by Western blotting. Finally, MET expression was evaluated by immunohistochemistry in a stomach tumor tissue microarray (TMA). Ectopic expression of miR-1 inhibited proliferation and migration in both AGS and SGC-7901 gastric cancer cell lines. miR-1 directly targets the MET gene and downregulates its expression. MET siRNA also inhibited proliferation and migration in both cell lines. Immunohistochemistry revealed significantly higher MET expression levels in gastric cancer tissues compared with matched adjacent non-cancer tissues. These findings indicate that the miR-1/MET pathway is a potential therapeutic target due to its crucial role in gastric cancer cell proliferation and migration. C1 [Han, Chao; Zhou, Yubing; An, Qi; Li, Feng; Li, Duolu; Zhang, Xiaojian; Kan, Quancheng] Zhengzhou Univ, Affiliated Hosp 1, Dept Clin Pharmacol, Zhengzhou 450052, Peoples R China. [Yu, Zujing] Zhengzhou Univ, Affiliated Hosp 1, Dept Infect Dis, Zhengzhou 450052, Peoples R China. [Zheng, Lili] Zhengzhou Univ, Affiliated Hosp 1, Dept Endocrinol & Metab, Zhengzhou 450052, Peoples R China. [Duan, Zhenfeng] Massachusetts Gen Hosp, Sarcoma Biol Lab, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. RP Kan, QC (reprint author), Zhengzhou Univ, Affiliated Hosp 1, Dept Clin Pharmacol, Zhengzhou 450052, Peoples R China. EM quanchengkan@yeah.net NR 40 TC 11 Z9 12 U1 3 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1010-4283 EI 1423-0380 J9 TUMOR BIOL JI Tumor Biol. PD SEP PY 2015 VL 36 IS 9 BP 6715 EP 6723 DI 10.1007/s13277-015-3358-6 PG 9 WC Oncology SC Oncology GA CW5KA UT WOS:000365033100016 PM 25874496 ER PT J AU Das, A Miller, R Lee, P Holden, CA Lindhorst, SM Jaboin, J Vandergrift, WA Banik, NL Giglio, P Varma, AK Raizer, JJ Patel, SJ AF Das, Arabinda Miller, Rickey Lee, Philip Holden, Chrysanthe Alyssa Lindhorst, Scott M. Jaboin, Jerry Vandergrift, William A., III Banik, Naren L. Giglio, Pierre Varma, Abhay K. Raizer, Jeffery J. Patel, Sunil J. TI A novel component from citrus, ginger, and mushroom family exhibits antitumor activity on human meningioma cells through suppressing the Wnt/beta-catenin signaling pathway SO TUMOR BIOLOGY LA English DT Article DE Meningioma; Apoptosis; Wnt; Catenin; Lemon; Ginger; Mushroom ID BREAST-CANCER CELLS; HUMAN GLIOBLASTOMA T98G; MALIGNANT MENINGIOMA; INDUCED APOPTOSIS; OXIDATIVE STRESS; GANODERIC ACID; U87MG CELLS; IOMM-LEE; KAPPA-B; INHIBITION AB Recurrent meningiomas constitute an uncommon but significant problem after standard (surgery and radiation) therapy failure. Current chemotherapies (hydroxyurea, RU-486, and interferon-alpha) are only of marginal benefit. There is an urgent need for more effective treatments for meningioma patients who have failed surgery and radiation therapy. Limonin, Tangeritin, Zerumbone, 6-Gingerol, Ganoderic Acid A, and Ganoderic Acid DM are some of the plant derivatives that have anti-tumorgenic properties and cause cell death in meningioma cells in vitro. Due to its ease of administration, long-term tolerability, and low incidence of long-term side effects, we explored its potential as a therapeutic agent against meningiomas by examining their efficacy in vitro against meningioma cells. Treatment effects were assessed using MTT assay, Western blot analysis, caspases assay, and DNA fragmentation assay. Results indicated that treatments of IOMM-Lee and CH157MN meningioma cells with Limonin, Tangeritin, Zerumbone, 6-Gingerol, Ganoderic Acid A, and Ganoderic Acid DM induced apoptosis with enhanced phosphorylation of glycogen synthase kinase 3 beta (GSK3 beta) via inhibition of the Wnt5/beta-catenin pathway. These drugs did not induce apoptosis in normal human neurons. Other events in apoptosis included downregulation of tetraspanin protein (TSPAN12), survival proteins (Bcl-XL and Mcl-1), and overexpression apoptotic factors (Bax and caspase-3). These results provide preliminary strong evidence that medicinal plants containing Limonin, Tangeritin, 6-Gingerol, Zerumbone, Ganoderic Acid A, and Ganoderic Acid DM can be applied to high-grade meningiomas as a therapeutic agent, and suggests that further in vivo studies are necessary to explore its potential as a therapeutic agent against malignant meningiomas. C1 [Das, Arabinda; Miller, Rickey; Lee, Philip; Holden, Chrysanthe Alyssa; Lindhorst, Scott M.; Vandergrift, William A., III; Banik, Naren L.; Giglio, Pierre; Varma, Abhay K.; Patel, Sunil J.] Med Univ S Carolina, Dept Neurosurg, Charleston, SC 29425 USA. [Jaboin, Jerry] Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO 63110 USA. [Banik, Naren L.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Giglio, Pierre] Ohio State Univ, Dept Neurol Surg, Wexner Med Coll, Columbus, OH 43210 USA. [Raizer, Jeffery J.] Northwestern Univ, Dept Neurol, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Raizer, Jeffery J.] Northwestern Univ, Northwestern Brain Tumor Inst, Robert H Lurie Comprehens Canc Ctr, Feinberg Sch Med, Chicago, IL 60611 USA. [Das, Arabinda] Med Univ S Carolina, Dept Neurosurg, MUSC Brain & Spine Tumor Program CSB 310, Neurooncol Div, Charleston, SC 29425 USA. RP Das, A (reprint author), Med Univ S Carolina, Dept Neurosurg, Charleston, SC 29425 USA. EM dasa@musc.edu FU Jerry Zucker Fund for Brain Tumor Research at the MUSC Foundation; Department of Neurosurgery (MUSC); American Brain Tumor Association; NIH [NS-38146, NS-41088]; Office of Research and Development, Department of Veterans Affairs [101BX001262] FX This investigation was supported by the Jerry Zucker Fund for Brain Tumor Research at the MUSC Foundation, Department of Neurosurgery (MUSC), American Brain Tumor Association (Medical Student Summer Fellowship in Honor of Paul Fabri), NIH grants (NS-38146, NS-41088), and also, this work in part was supported by a merit award from the Office of Research and Development, Department of Veterans Affairs (101BX001262). NR 36 TC 4 Z9 4 U1 2 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1010-4283 EI 1423-0380 J9 TUMOR BIOL JI Tumor Biol. PD SEP PY 2015 VL 36 IS 9 BP 7027 EP 7034 DI 10.1007/s13277-015-3388-0 PG 8 WC Oncology SC Oncology GA CW5KA UT WOS:000365033100051 PM 25864108 ER PT J AU Mousavi, N Tan, TC Ali, M Halpern, EF Wang, L Scherrer-Crosbie, M AF Mousavi, Negareh Tan, Timothy C. Ali, Mohammed Halpern, Elkan F. Wang, Lin Scherrer-Crosbie, Marielle TI Echocardiographic parameters of left ventricular size and function as predictors of symptomatic heart failure in patients with a left ventricular ejection fraction of 50-59% treated with anthracyclines SO EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING LA English DT Article DE chemotherapy; echocardiography; heart failure; left ventricular function; strain; anthracycline ID BREAST-CANCER; INDUCED CARDIOTOXICITY; MYOCARDIAL STRAIN; CHEMOTHERAPY; DOXORUBICIN; THERAPY; CARDIOMYOPATHY; TRASTUZUMAB; REPRODUCIBILITY; LYMPHOMA AB Aims The aim of this study was to assess whether baseline echocardiographic measures of left ventricular (LV) size and function predict the development of symptomatic heart failure or cardiac death (major adverse cardiac events, MACE) in patients treated with anthracyclines who have a pre-chemotherapy left ventricular ejection fraction (LVEF) between 50 and 59%. Methods and results Patients with an LVEF between 50 and 59% before anthracyclineswere selected. In these patients, LV volumes, LVEF, and peak longitudinal strain (GLS) were measured. Individualswere followed forMACE and all-cause mortality over a median of 659 days (range: 3-3704 days). Of 2234 patients undergoing echocardiography for pre-anthracycline assessment, 158 (7%) had a resting ejection fraction of 50-59%. Their average LV end-diastolic volume (LVEDV) was 101 +/- 22 mL, LVEF was 54 +/- 3%, and global longitudinal strain (GLS) was 117.7 +/- 2.6%. Twelve patients experienced aMACE (congestive heart failure) at a median of 173 days (range: 15-530). Age, diabetes, previous coronary artery disease, LVEDV, indexed LVEDV, LVESV, indexed LVESV, and GLS were all predictive of MACE (P 0.012, 0.039, 0.0029, 0.012, and 0.0065 for LVEDV, LVEDVI, LVESV, LVESVI, and GLS, respectively). Indexed LVEDV and GLS remained predictive of MACE when adjusted for age. Age and GLS were also predictive of overall mortality (P < 0.0001 and 0.0105, respectively). Conclusion In patients treated with anthracyclines with an LVEF of 50-59%, both baseline EDV and GLS predict the occurrence of MACE. These parameters may help target patients who could benefit from closer cardiac surveillance and earlier initiation of cardioprotective medical therapy. C1 [Mousavi, Negareh; Tan, Timothy C.; Ali, Mohammed; Wang, Lin; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Mousavi, Negareh; Tan, Timothy C.; Ali, Mohammed; Halpern, Elkan F.; Wang, Lin; Scherrer-Crosbie, Marielle] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Halpern, Elkan F.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Scherrer-Crosbie, M (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 55 Fruit St, Boston, MA 02114 USA. EM marielle@crosbie.com NR 34 TC 9 Z9 9 U1 1 U2 3 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 SEP PY 2015 VL 16 IS 9 BP 977 EP 984 DI 10.1093/ehjci/jev113 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CV8LS UT WOS:000364539700008 PM 25925220 ER PT J AU Lee, DC Long, JA Wall, SP Carr, BG Satchell, SN Braithwaite, S Elbel, B AF Lee, David C. Long, Judith A. Wall, Stephen P. Carr, Brendan G. Satchell, Samantha N. Braithwaite, Scott Elbel, Brian TI Determining Chronic Disease Prevalence in Local Populations Using Emergency Department Surveillance SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID PUBLIC-HEALTH; DIABETES CARE; IMPROVE; OBESITY; SYSTEM; IMPACT; STATES AB Objectives. We sought to improve public health surveillance by using a geographic analysis of emergency department (ED) visits to determine local chronic disease prevalence. Methods. Using an all-payer administrative database, we determined the proportion of unique ED patients with diabetes, hypertension, or asthma. We compared these rates to those determined by the New York City Community Health Survey. For diabetes prevalence, we also analyzed the fidelity of longitudinal estimates using logistic regression and determined disease burden within census tracts using geocoded addresses. Results. We identified 4.4 million unique New York City adults visiting an ED between 2009 and 2012. When we compared our emergency sample to survey data, rates of neighborhood diabetes, hypertension, and asthma prevalence were similar (correlation coefficient = 0.86, 0.88, and 0.77, respectively). In addition, our method demonstrated less year-to-year scatter and identified significant variation of disease burden within neighborhoods among census tracts. Conclusions. Our method for determining chronic disease prevalence correlates with a validated health survey and may have higher reliability over time and greater granularity at a local level. Our findings can improve public health surveillance by identifying local variation of disease prevalence. C1 [Lee, David C.; Wall, Stephen P.] NYU, Sch Med, Ronald O Perelman Dept Emergency Med, New York, NY USA. [Braithwaite, Scott; Elbel, Brian] NYU, Sch Med, Dept Populat Hlth, New York, NY USA. [Long, Judith A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. [Carr, Brendan G.] Thomas Jefferson Univ, Sidney Kimmel Med Coll, Dept Emergency Med, Philadelphia, PA 19107 USA. [Satchell, Samantha N.] George Washington Univ, Milken Inst, Sch Publ Hlth, Washington, DC USA. RP Lee, DC (reprint author), Dept Emergency Med, 462 First Ave,Room A345, New York, NY 10016 USA. EM david.lee@nyumc.org OI Wall, Stephen/0000-0003-3965-5074; Elbel, Brian/0000-0003-1615-9430 FU University of Pennsylvania; Leonard Davis Institute of Health Economics; Robert Wood Johnson Foundation Health and Society Scholars Program; Robert Wood Johnson Foundation Clinical Scholars Program FX This study was funded by 2 intramural grants from the University of Pennsylvania: a health services research grant from the Leonard Davis Institute of Health Economics and a population health research grant from the Robert Wood Johnson Foundation Health and Society Scholars Program. D. C. Lee was also supported by the fellowship and faculty mentorship at the Robert Wood Johnson Foundation Clinical Scholars Program. NR 46 TC 3 Z9 3 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2015 VL 105 IS 9 BP E67 EP E74 DI 10.2105/AJPH.2015.302679 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CV5PG UT WOS:000364322600017 PM 26180983 ER PT J AU Dalli, J Kraft, BD Colas, RA Shinohara, M Fredenburgh, LE Hess, DR Chiang, N Welty-Wolf, K Choi, AM Piantadosi, CA Serhan, CN AF Dalli, Jesmond Kraft, Bryan D. Colas, Romain A. Shinohara, Masakazu Fredenburgh, Laura E. Hess, Dean R. Chiang, Nan Welty-Wolf, Karen Choi, Augustine M. Piantadosi, Claude A. Serhan, Charles N. TI The Regulation of Proresolving Lipid Mediator Profiles in Baboon Pneumonia by Inhaled Carbon Monoxide SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE inflammation resolution; therapeutic carbon monoxide; pneumonia; bacterial ID PRO-RESOLVING MEDIATORS; INDUCED LUNG INJURY; ANTIINFLAMMATORY THERAPY; MITOCHONDRIAL BIOGENESIS; INFLAMMATION-RESOLUTION; PLATELET-AGGREGATION; CHILDHOOD PNEUMONIA; SEPSIS; INHIBITION; MODEL AB Strategies for the treatment of bacterial pneumonia beyond traditional antimicrobial therapy have been limited. The recently discovered novel genus of lipid mediators, coined "specialized proresolving mediators" (SPMs), which orchestrate clearance of recruited leukocytes and restore epithelial barrier integrity, have offered new insight into the resolution of inflammation. We performed lipid mediator (LM) metabololipidomic profiling and identification of LMs on peripheral blood leukocytes and plasma from a baboon model of Streptococcus pneumoniae pneumonia. Leukocytes and plasma were isolated from whole blood of S. pneumoniae-infected (n = 5-6 per time point) and control, uninfected baboons (n = 4 per time point) at 0, 24, 48, and 168 hours. In a subset of baboons with pneumonia (n = 3), we administered inhaled carbon monoxide (CO) at 48 hours (200-300 ppm for 60-90 min). Unstimulated leukocytes from control animals produced a proresolving LM signature with elevated resolvins and lipoxins. In contrast, serum-treated, zymosan-stimulated leukocytes and leukocytes from baboons with S. pneumoniae pneumonia produced a proinflammatory LM signature profile with elevated leukotriene B-4 and prostaglandins. Plasma from baboons with S. pneumoniae pneumonia also displayed significantly reduced LM-SPM levels, including eicosapentaenoic acid-derived E-series resolvins (RvE) and lipoxins. CO inhalation increased levels of plasma RvE and lipoxins relative to preexposure levels. These results establish the leukocyte and plasma LM profiles biosynthesized during S. pneumoniae pneumonia in baboons and provide evidence for pneumonia-induced dysregulation of these proresolution programs. Moreover, these SPM profiles are partially restored with inhaled low-dose CO and SPM, which may shorten the time to pneumonia resolution. C1 [Dalli, Jesmond; Colas, Romain A.; Shinohara, Masakazu; Chiang, Nan; Serhan, Charles N.] Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Fredenburgh, Laura E.] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Kraft, Bryan D.; Welty-Wolf, Karen; Piantadosi, Claude A.] Duke Univ, Med Ctr, Dept Med, Div Pulm Allergy & Crit Care Med, Durham, NC 27710 USA. [Hess, Dean R.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Hess, Dean R.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Choi, Augustine M.] Weill Cornell Med Coll, Weill Dept Med, Div Pulm & Crit Care Med, New York, NY USA. RP Serhan, CN (reprint author), Harvard Inst Med, 77 Ave Louis Pasteur,HIM 829, Boston, MA 02115 USA. EM cnserhan@zeus.bwh.harvard.edu FU National Institutes of Health [P01-HL108801, P01-GM095467]; Gates Foundation Global Health Institute FX This work was supported by National Institutes of Health grants P01-HL108801 and P01-GM095467 and by the Gates Foundation Global Health Institute. NR 48 TC 8 Z9 8 U1 0 U2 0 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 SEP PY 2015 VL 53 IS 3 BP 314 EP 325 DI 10.1165/rcmb.2014-0299OC PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA CV5TR UT WOS:000364334600004 PM 25568926 ER PT J AU Sedaghat, AR Metson, R Gray, ST AF Sedaghat, Ahmad R. Metson, Ralph Gray, Stacey T. TI Impact of day of week on outcomes of endoscopic sinus surgery for chronic rhinosinusitis SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article ID ELECTIVE SURGERY; COMPLICATIONS; MORTALITY AB Background: Outcomes for some surgical procedures are discrepantly affected by the day of the week when surgery is performed. It remains unknown whether this finding is applicable to endoscopic sinus surgery (ESS). Methods: A retrospective analysis of a cohort from a prospective observational study of patients undergoing ESS for chronic rhinosinusitis. Primary outcome measures included major postoperative complications (epistaxis that required physician intervention, orbital injury, and cerebrospinal fluid leak) as well as Sinonasal Outcomes Test 22 (SNOT-22) and Chronic Sinusitis Survey (CSS) quality-of-life symptom scores at 3 months, 1 year, and 2 years. Associations between the day of the week when ESS was performed and outcome measures were performed when controlling for patients' clinical and demographic characteristics. Results: The study population consisted of 544 patients with a 30-day major postoperative complications rate of 1.2%. There was no predilection for ESS complications by the day of the week. In comparison with ESS on a Monday, improvement in the SNOT-22 score was no different than with ESS performed on Tuesday (p = 0.800 at 3 months, p = 0.149 at 12 months, p = 0.123 at 24 months), Wednesday (p = 0.533 at 3 months, p = 0.708 at 12 months, p = 0.107 at 24 months), and Thursday (p = 0.965 at 3 months, p = 0.959 at 12 months, p = 0.501 at 24 months). No surgeries were performed on Friday. Similar results were found for improvement in CSS scores. Conclusion: The day of the week on which ESS was performed did not impact surgical outcomes. These results provided novel insights, which may be useful for preoperative discussions with patients and scheduling of ESS. C1 [Gray, Stacey T.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Gray, ST (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM stacey_gray@meei.harvard.edu FU Board Committee on Quality, Massachusetts Eye and Ear Infirmary FX This work was supported by a funding grant from the Board Committee on Quality, Massachusetts Eye and Ear Infirmary NR 13 TC 1 Z9 1 U1 0 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 SEP-OCT PY 2015 VL 29 IS 5 BP 378 EP 382 DI 10.2500/ajra.2015.29.4228 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA CV5UR UT WOS:000364337200020 PM 26358351 ER PT J AU Gutu, AD Rodgers, NS Park, J Moskowitz, SM AF Gutu, Alina D. Rodgers, Nicole S. Park, Jihye Moskowitz, Samuel M. TI Pseudomonas aeruginosa High-Level Resistance to Polymyxins and Other Antimicrobial Peptides Requires cprA, a Gene That Is Disrupted in the PAO1 Strain SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID 2-COMPONENT REGULATORY SYSTEM; CYSTIC-FIBROSIS PATIENTS; GRAM-NEGATIVE BACTERIA; OUTER-MEMBRANE VESICLES; ESCHERICHIA-COLI; PMRA-PMRB; LIPID-A; PHOP-PHOQ; ACINETOBACTER-BAUMANNII; ADAPTIVE RESISTANCE AB The arn locus, found in many Gram-negative bacterial pathogens, mediates resistance to polymyxins and other cationic antimicrobial peptides through 4-amino-L-arabinose modification of the lipid A moiety of lipopolysaccharide. In Pseudomonas aeruginosa, several two-component regulatory systems (TCSs) control the arn locus, which is necessary but not sufficient for these resistance phenotypes. A previous transposon mutagenesis screen to identify additional polymyxin resistance genes that these systems regulate implicated an open reading frame designated PA1559 in the genome of the P. aeruginosa PAO1 strain. Resequencing of this chromosomal region and bioinformatics analysis for a variety of P. aeruginosa strains revealed that in the sequenced PAO1 strain, a guanine deletion at the end of PA1559 results in a frameshift and truncation of a full-length open reading frame that also encompasses PA1560 in non-PAO1 strains, such as P. aeruginosa PAK. Deletion analysis in the PAK strain showed that this full-length open reading frame, designated cprA, is necessary for polymyxin resistance conferred by activating mutations in the PhoPQ, PmrAB, and CprRS TCSs. The cprA gene was also required for PmrAB-mediated resistance to other cationic antimicrobial peptides in the PAK strain. Repair of the mutated cprA allele in the PAO1 strain restored polymyxin resistance conferred by an activating TCS mutation. The deletion of cprA did not affect the arn-mediated lipid A modification, indicating that the CprA protein is necessary for a different aspect of polymyxin resistance. This protein has a domain structure with a strong similarity to the extended short-chain dehydrogenase/reductase family that comprises isomerases, lyases, and oxidoreductases. These results suggest a new avenue through which to pursue targeted inhibition of polymyxin resistance. C1 [Gutu, Alina D.; Rodgers, Nicole S.; Park, Jihye; Moskowitz, Samuel M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Park, Jihye; Moskowitz, Samuel M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Moskowitz, SM (reprint author), Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. EM smoskowitz@mgh.harvard.edu FU CF Foundation [MOSKOW13P0] FX This work was supported by grant MOSKOW13P0 to S.M.M. from the CF Foundation. NR 67 TC 3 Z9 4 U1 3 U2 14 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 SEP PY 2015 VL 59 IS 9 BP 5377 EP 5387 DI 10.1128/AAC.00904-15 PG 11 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA CV5XD UT WOS:000364343900036 PM 26100714 ER PT J AU Kim, ES Chen, CH Braun, M Kim, HY Okumura, R Wang, Y Jacoby, GA Hooper, DC AF Kim, Eu Suk Chen, Chunhui Braun, Molly Kim, Hyo Youl Okumura, Ryo Wang, Yin Jacoby, George A. Hooper, David C. TI Interactions between QnrB, QnrB Mutants, and DNA Gyrase SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID MEDIATED QUINOLONE RESISTANCE; PENTAPEPTIDE REPEAT PROTEINS; ESCHERICHIA-COLI; TRANSFERABLE PLASMID; MUTATIONAL ANALYSIS; GENE; MECHANISMS; COMPLEX; STRAND AB Plasmid-encoded protein QnrB1 protects DNA gyrase from ciprofloxacin inhibition. Using a bacterial two-hybrid system, we evaluated the physical interactions between wild-type and mutant QnrB1, the GyrA and GyrB gyrase subunits, and a GyrBA fusion protein. The interaction of QnrB1 with GyrB and GyrBA was approximately 10-fold higher than that with GyrA, suggesting that domains of GyrB are important for stabilizing QnrB1 interaction with the holoenzyme. Sub-MICs of ciprofloxacin or nalidixic acid reduced the interactions between QnrB1 and GyrA or GyrBA but produced no reduction in the interaction with GyrB or a quinolone-resistant GyrA: S83L (GyrA with S83L substitution) mutant, suggesting that quinolones and QnrB1 compete for binding to gyrase. Of QnrB1 mutants that reduced quinolone resistance, deletions in the C or N terminus of QnrB1 resulted in a marked decrease in interactions with GyrA but limited or no effect on interactions with GyrB and an intermediate effect on interactions with GyrBA. While deletion of loop B and both loops moderately reduced the interaction signal with GyrA, deletion of loop A resulted in only a small reduction in the interaction with GyrB. The loop A deletion also caused a substantial reduction in interaction with GyrBA, with little effect of loop B and dual-loop deletions. Single-amino-acid loop mutations had little effect on physical interactions except for a Delta 105I mutant. Therefore, loops A and B may play key roles in the proper positioning of QnrB1 rather than as determinants of the physical interaction of QnrB1 with gyrase. C1 [Kim, Eu Suk; Chen, Chunhui; Braun, Molly; Kim, Hyo Youl; Okumura, Ryo; Wang, Yin; Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Kim, Eu Suk] Seoul Natl Univ, Bundang Hosp, Dept Internal Med, Songnam, South Korea. [Chen, Chunhui] Fudan Univ, Huashan Hosp, Inst Antibiot, Shanghai 200433, Peoples R China. [Chen, Chunhui] Natl Hlth & Family Planning Commiss, Key Lab Clin Pharmacol Antibiot, Shanghai, Peoples R China. [Kim, Hyo Youl] Yonsei Univ, Wonju Coll Med, Dept Internal Med, Wonju, South Korea. [Okumura, Ryo] Daiichi Sankyo Co Ltd, Biol Res Labs, Tokyo, Japan. [Jacoby, George A.] Lahey Hosp & Med Ctr, Burlington, MA USA. RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM dhooper@mgh.harvard.edu FU U.S. Public Health Service, National Institutes of Health [R01 AI057576] FX This work was supported in part by a grant from the U.S. Public Health Service, National Institutes of Health, R01 AI057576 (to D.C.H. and G.A.J.). NR 32 TC 3 Z9 3 U1 0 U2 3 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 SEP PY 2015 VL 59 IS 9 BP 5413 EP 5419 DI 10.1128/AAC.00771-15 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA CV5XD UT WOS:000364343900040 PM 26100716 ER PT J AU Shields, RK Clancy, CJ Hao, BH Chen, L Press, EG Iovine, NM Kreiswirth, BN Nguyen, MH AF Shields, Ryan K. Clancy, Cornelius J. Hao, Binghua Chen, Liang Press, Ellen G. Iovine, Nicole M. Kreiswirth, Barry N. Nguyen, M. Hong TI Effects of Klebsiella pneumoniae Carbapenemase Subtypes, Extended-Spectrum beta-Lactamases, and Porin Mutations on the In Vitro Activity of Ceftazidime-Avibactam against Carbapenem-Resistant K. pneumoniae SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID US MEDICAL-CENTERS; SEQUENCE TYPE 258; DORIPENEM; COLISTIN; STRAINS; ENTEROBACTERIACEAE; COMBINATION; BACTEREMIA; RESPONSES; GENOTYPES AB Avibactam is a novel beta-lactamase inhibitor with affinity for Klebsiella pneumoniae carbapenemases (KPCs). In combination with ceftazidime, the agent demonstrates activity against KPC-producing K. pneumoniae (KPC-Kp). KPC-Kp strains are genetically diverse and harbor multiple resistance determinants, including defects in outer membrane proteins and extended-spectrum beta-lactamases (ESBLs). Mutations in porin gene ompK36 confer high-level carbapenem resistance to KPC-Kp strains. Whether specific mechanisms of antimicrobial resistance also influence the activity of ceftazidime-avibactam is unknown. We defined the effects of ceftazidime-avibactam against 72 KPC-Kp strains with diverse mechanisms of resistance, including various combinations of KPC subtypes and ESBL and ompK36 mutations. Ceftazidime MICs ranged from 64 to 4,096 mu g/ml and were lowered by a median of 512-fold with the addition of avibactam. All strains exhibited ceftazidime-avibactam MICs at or below the CLSI breakpoint for ceftazidime (<= 4 mu g/ml; range, 0.25 to 4). However, the MICs were within two 2-fold dilutions of the CLSI breakpoint against 24% of the strains, and those strains would be classified as nonsusceptible to ceftazidime by EUCAST criteria (MIC > 1 mu g/ml). Median ceftazidime-avibactam MICs were higher against KPC-3 than KPC-2 variants (P = 0.02). Among KPC-2-Kp strains, the presence of both ESBL and porin mutations was associated with higher drug MICs compared to those seen with either factor alone (P = 0.003 and P = 0.02, respectively). In conclusion, ceftazidime-avibactam displays activity against genetically diverse KPC-Kp strains. Strains with higher-level drug MICs provide a reason for caution. Judicious use of ceftazidime-avibactam alone or in combination with other agents will be important to prevent the emergence of resistance. C1 [Shields, Ryan K.; Clancy, Cornelius J.; Press, Ellen G.; Nguyen, M. Hong] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. [Shields, Ryan K.; Nguyen, M. Hong] Univ Pittsburgh, Med Ctr, Antibiot Management Program, Pittsburgh, PA USA. [Shields, Ryan K.; Clancy, Cornelius J.; Hao, Binghua; Nguyen, M. Hong] Univ Pittsburgh, Med Ctr, XDR Pathogen Lab, Pittsburgh, PA USA. [Clancy, Cornelius J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Chen, Liang; Kreiswirth, Barry N.] Rutgers State Univ, New Jersey Med Sch, Publ Hlth Res Inst, Newark, NJ 07102 USA. [Iovine, Nicole M.] Univ Florida, Dept Med, Gainesville, FL USA. RP Clancy, CJ (reprint author), Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. EM cjc76@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 number KL2 RR024154 (awarded to R.K.S.). NR 17 TC 14 Z9 15 U1 0 U2 5 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 SEP PY 2015 VL 59 IS 9 BP 5793 EP 5797 DI 10.1128/AAC.00548-15 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA CV5XD UT WOS:000364343900085 PM 26169413 ER PT J AU Robb, JA Bry, L Sluss, PM Wagar, EA Kennedy, MF AF Robb, James A. Bry, Lynn Sluss, Patrick M. Wagar, Elizabeth A. Kennedy, Mary F. CA Coll Amer Pathologists TI A Call to Standardize Preanalytic Data Elements for Biospecimens, Part II SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article AB Context.-Biospecimens must have appropriate clinical annotation (data) to ensure optimal quality for both patient care and research. Additional clinical preanalytic variables are the focus of this continuing study. Objective.-To complete the identification of the essential preanalytic variables (data fields) that can, and in some instances should, be attached to every collected biospecimen by adding the additional specific variables for clinical chemistry and microbiology to our original 170 variables. Design.-The College of American Pathologists Diagnostic Intelligence and Health Information Technology Committee sponsored a second Biorepository Working Group to complete the list of preanalytic variables for annotating biospecimens. Members of the second Biorepository Working Group are experts in clinical pathology and microbiology. Additional preanalytic area-specific variables were identified and ranked along with definitions and potential negative impacts if the variable is not attached to the biospecimen. The draft manuscript was reviewed by additional national and international stakeholders. Results.-Four additional required preanalytic variables were identified specifically for clinical chemistry and microbiology biospecimens that can be used as a guide for site-specific implementation into patient care and research biorepository processes. Conclusions.-In our collective experience, selecting which of the many preanalytic variables to attach to any specific set of biospecimens used for patient care and/or research is often difficult. The additional ranked list should be of practical benefit when selecting preanalytic variables for a given biospecimen collection. C1 [Bry, Lynn] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Sluss, Patrick M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Wagar, Elizabeth A.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Kennedy, Mary F.] Coll Amer Pathologists, Northfield, IL 60093 USA. RP Kennedy, MF (reprint author), Coll Amer Pathologists, 325 Waukegan Rd, Northfield, IL 60093 USA. EM mkenned@cap.org NR 2 TC 1 Z9 1 U1 0 U2 1 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 EI 1543-2165 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD SEP PY 2015 VL 139 IS 9 BP 1125 EP 1128 DI 10.5858/arpa.2014-0572-CP PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA CV8DX UT WOS:000364510300007 PM 25594725 ER PT J AU Ghert, M Bhandari, M Deheshi, B Guyatt, G Holt, G O'Shea, T Randall, RL Thabane, L Wunder, J Evaniew, N McKay, P Schneider, P Turcotte, R Madden, K Scott, T Sprague, S Simunovic, N Swinton, M Racano, A Heels-Ansdell, D Buckingham, L Rose, P Brigman, B Pullenayegum, E Ghert, M Evaniew, N Mckay, P Schneider, P Sobhi, G Chan, R Biljan, M Ferguson, P Wunder, J Griffin, A Mantas, I Wylie, A Han, A Grewal, G Turcotte, R Goulding, K Dandachli, F Matte, G Werier, J Abdelbary, H Paquin, K Cosgrove, H Dugal, AM Fetzer, S Aikens, W Clarkson, P Wang, B Kondo, L Yip, J Isler, M Mottard, S Barry, J St Yves, H Quach, M Assayag, H Daoust, K Goyette, K Projean, D Dion, N Arteau, A Turmel, S Bertrand, A Gagnon, N Labbe, V Holt, G Halpern, J Schwartz, H Atkinson, A Daniels, J Moore, MS Anderson, M Gebhardt, M Wagner, K Patel, H Jolin, H Anderson, M Gebhardt, M Allar, B Naqvi, M Bennett, J Albuquerque, S Randall, RL Jones, K Crabtree, S Davis, R Sorenson, S Healey, JH Galle, J O'Neill, G Del Corral, B Lopez, S Serra, MG Parizzia, W Podrzaj, A Torres, MF Clayer, M Chai, Y Slobodian, P Balach, T Coyle, K LaCasse, R Abraham, J Morrison, T Angelos, M Sailor, L Sadaka, R Miller, B Milhem, M McCurdy, N Kain, J Nohr, J Johnson, K Merriss, A Cheng, E Luke, DG Scharschmidt, TJ Crist, MK Dimeo, A Marmon, L Reimer, N Monson, D Oskouei, S Lomba, C Rogers, S Avedian, R Jordan, L Chinn, S Hamilton, M Ghert, M Evaniew, N McKay, P Schneider, P Sobhi, G Chan, R Bil-Jan, M Ferguson, P Wunder, J Griffin, A Mantas, I Wylie, A Han, A Grewal, G Turcotte, R Goulding, K Dandachli, F Matte, G Werier, J Abdelbary, H Paquin, K Cosgrove, H Dugal, AM Fetzer, S Aikens, W Clarkson, P Wang, B Kondo, L Yip, J Isler, M Mottard, S Barry, J Yves, HS Quach, M Assayag, H Daoust, K Goyette, K Projean, D Dion, N Arteau, A Turmel, S Bertrand, A Gagnon, N Labbe, V Holt, G Halpern, J Schwartz, H Atkinson, A Daniels, J Moore, MS Anderson, M Gebhardt, M Wagner, K Patel, H Jolin, H Anderson, M Gebhardt, M Allar, B Naqvi, M Bennett, J Albuquerque, S Randall, RL Jones, K Crabtree, S Davis, R Sorenson, S Healey, JH Galle, J O'Neill, G Del Corral, B Lopez, S Serra, MG Parizzia, W Podrzaj, A Torres, MF Clayer, M Tran, N Slobodian, P Balach, T Coyle, K LaCasse, R Abraham, J Morrison, T Angelos, M Sailor, L Sadaka, R Miller, B Milhem, M McCurdy, N Kain, J Nohr, J Johnson, K Merriss, A Cheng, E Luke, DG Scharschmidt, TJ Crist, MK Dimeo, A Marmon, L Reimer, N Monson, D Oskouei, S Lomba, C Rogers, S Geller, D Hoang, B Tingling, J Solorzano, C Avedian, R Jordan, L Chinn, S Hamilton, M Puloski, S Monument, M Carcary, K Cameron, C Aboulafia, A Loo-Mis, M Bosley, J Bonvegna, R Kassa, M Damron, T Craig, T Reale, M Goodman, HJ Culbertson, MD Caruso, P Garling, E Schwab, J Fiore, A Phukan, R Park, C Joshi, L Aboulafia, A Wallace, M Flack, J Vaughan, K Avergas, A Brady, M Brown, S Schadie, N Battersby, R Weiss, K Goodman, M Heyl, A Yeschke, CA Sumic, P Dudgeon, M Prosser, R Korenoski, C DiCaprio, M Palmer, B Cioppa, E Schaeffer, TM Paul, P Toreson, J Cummings, J Schwartz, L Zahner, B Morris, C Laljani, V Mesko, N Joyce, M Lietman, S Wustrack, R O'Donnell, R Stevenson, C Carmody, E Tyler, W McIntyre, A Spiguel, A Scarborough, M Gibbs, CP Steshyn, J Nunn, B Rosenthal, H Haynes, K Leddy, L Walton, Z Doung, YC Hayden, J Velez, R Aguirre, M Perez, M Barrera, S Lopez, AG Grimer, R Dunn, K Virdee, H Rankin, K Beckingsale, T Gerrand, C Campbell, I Allen, M Khan, SA Bakshi, S Rastogi, S Poudel, R Kumar, VS Rai, A Baptista, AM de Camargo, OP Marais, L Rodseth, R Ferreira, N Rajah, C Gumede, S Gortzak, Y Sternheim, A Bickels, J Kolander, Y Lev, S Hettwer, W Petersen, MM Grum-Schwensen, T Jutte, P Ploegmakers, JJW Stevens, M Mahendra, A Gupta, S Bergovec, M Leithner, A Funovics, P Dijkstra, PDS Van De Sande, M Hoogenstraaten, A Leijerzapf, N Steadman, P Steadman, P Boffano, M Piana, R Marone, S Albertini, U Boux, E Maiello, A Repsa, L Zile, S Aston, W Pollock, R Cool, P Gibbons, M Whit-Well, D Cosker, T Hemingway, J Porter, D Patton, S Navia, J Betancur, AF Laitenen, M Pakarinen, K Nieminen, J Yla-Mononen, S Rautiainen, S Fiorenza, F AF Ghert, M. Bhandari, M. Deheshi, B. Guyatt, G. Holt, G. O'Shea, T. Randall, R. L. Thabane, L. Wunder, J. Evaniew, N. McKay, P. Schneider, P. Turcotte, R. Madden, K. Scott, T. Sprague, S. Simunovic, N. Swinton, M. Racano, A. Heels-Ansdell, D. Buckingham, L. Rose, P. Brigman, B. Pullenayegum, E. Ghert, M. Evaniew, N. Mckay, P. Schneider, P. Sobhi, G. Chan, R. Biljan, M. Ferguson, P. Wunder, J. Griffin, A. Mantas, I. Wylie, A. Han, A. Grewal, G. Turcotte, R. Goulding, K. Dandachli, F. Matte, G. Werier, J. Abdelbary, H. Paquin, K. Cosgrove, H. Dugal, A-M. Fetzer, S. Aikens, W. Clarkson, P. Wang, B. Kondo, L. Yip, J. Isler, M. Mottard, S. Barry, J. St Yves, H. Quach, M. Assayag, H. Daoust, K. Goyette, K. Projean, D. Dion, N. Arteau, A. Turmel, S. Bertrand, A. Gagnon, N. Labbe, V. Holt, G. Halpern, J. Schwartz, H. Atkinson, A. Daniels, J. Moore, M. S. Anderson, M. Gebhardt, M. Wagner, K. Patel, H. Jolin, H. Anderson, M. Gebhardt, M. Allar, B. Naqvi, M. Bennett, J. Albuquerque, S. Randall, R. L. Jones, K. Crabtree, S. Davis, R. Sorenson, S. Healey, J. H. Galle, J. O'Neill, G. Del Corral, B. Lopez, S. Galli Serra, M. Parizzia, W. Podrzaj, A. Foa Torres, M. Clayer, M. Chai, Y. Slobodian, P. Balach, T. Coyle, K. LaCasse, R. Abraham, J. Morrison, T. Angelos, M. Sailor, L. Sadaka, R. Miller, B. Milhem, M. McCurdy, N. Kain, J. Nohr, J. Johnson, K. Merriss, A. Cheng, E. Luke, D. G. Scharschmidt, T. J. Crist, M. K. Dimeo, A. Marmon, L. Reimer, N. Monson, D. Oskouei, S. Lomba, C. Rogers, S. Avedian, R. Jordan, L. Chinn, S. Hamilton, M. Ghert, M. Evaniew, N. McKay, P. Schneider, P. Sobhi, G. Chan, R. Bil-Jan, M. Ferguson, P. Wunder, J. Griffin, A. Mantas, I. Wylie, A. Han, A. Grewal, G. Turcotte, R. Goulding, K. Dandachli, F. Matte, G. Werier, J. Abdelbary, H. Paquin, K. Cosgrove, H. Dugal, A-M. Fetzer, S. Aikens, W. Clarkson, P. Wang, B. Kondo, L. Yip, J. Isler, M. Mottard, S. Barry, J. Yves, H. St. Quach, M. Assayag, H. Daoust, K. Goyette, Kristine Projean, D. Dion, N. Arteau, A. Turmel, S. Bertrand, A. Gagnon, N. Labbe, V. Holt, G. Halpern, J. Schwartz, H. Atkinson, A. Daniels, J. Moore, M. S. Anderson, M. Gebhardt, M. Wagner, K. Patel, H. Jolin, H. Anderson, M. Gebhardt, M. Allar, B. Naqvi, M. Bennett, J. Albuquerque, S. Randall, R. L. Jones, K. Crabtree, S. Davis, R. Sorenson, S. Healey, J. H. Galle, J. O'Neill, G. Del Corral, B. Lopez, S. Galli Serra, M. Parizzia, W. Podrzaj, A. Foa Torres, M. Clayer, M. Tran, N. Slobodian, P. Balach, T. Coyle, K. LaCasse, R. Abraham, J. Morrison, T. Angelos, M. Sailor, L. Sadaka, R. Miller, B. Milhem, M. McCurdy, N. Kain, J. Nohr, J. Johnson, K. Merriss, A. Cheng, E. Luke, D. G. Scharschmidt, T. J. Crist, M. K. Dimeo, A. Marmon, L. Reimer, N. Monson, D. Oskouei, S. Lomba, C. Rogers, S. Geller, D. Hoang, B. Tingling, J. Solorzano, C. Avedian, R. Jordan, L. Chinn, S. Hamilton, M. Puloski, S. Monument, M. Carcary, K. Cameron, C. Aboulafia, A. Loo-Mis, M. Bosley, J. Bonvegna, R. Kassa, M. Damron, T. Craig, T. Reale, M. Goodman, H. J. Culbertson, M. Deza Caruso, P. Garling, E. Schwab, J. Fiore, A. Phukan, R. Park, C. Joshi, L. Aboulafia, A. Wallace, M. Flack, J. Vaughan, K. Avergas, A. Brady, M. Brown, S. Schadie, N. Battersby, R. Weiss, K. Goodman, M. Heyl, A. Yeschke, C. A. Sumic, P. Dudgeon, M. Prosser, R. Korenoski, C. DiCaprio, M. Palmer, B. Cioppa, E. Schaeffer, T. M. Paul, P. Toreson, J. Cummings, J. Schwartz, L. Zahner, B. Morris, C. Laljani, V. Mesko, N. Joyce, M. Lietman, S. Wustrack, R. O'Donnell, R. Stevenson, C. Carmody, E. Tyler, W. McIntyre, A. Spiguel, A. Scarborough, M. Gibbs, C. P. Steshyn, J. Nunn, B. Rosenthal, H. Haynes, K. Leddy, L. Walton, Z. Doung, Y-C. Hayden, J. Velez, R. Aguirre, M. Perez, M. Barrera, S. Garca Lopez, A. Grimer, R. Dunn, K. Virdee, H. Rankin, K. Beckingsale, T. Gerrand, C. Campbell, I. Allen, M. Khan, S. Alam Bakshi, S. Rastogi, S. Poudel, R. Kumar, V. Sampath Rai, A. Baptista, A. M. de Camargo, O. P. Marais, L. Rodseth, R. Ferreira, N. Rajah, C. Gumede, S. Gortzak, Y. Sternheim, A. Bickels, J. Kolander, Y. Lev, S. Hettwer, W. Petersen, M. M. Grum-Schwensen, T. Jutte, P. Ploegmakers, J. J. W. Stevens, M. Mahendra, A. Gupta, S. Bergovec, M. Leithner, A. Funovics, P. Dijkstra, P. D. S. Van De Sande, M. Hoogenstraaten, A. Leijerzapf, N. Steadman, P. Steadman, P. Boffano, M. Piana, R. Marone, S. Albertini, U. Boux, E. Maiello, A. Repsa, L. Zile, S. Aston, W. Pollock, R. Cool, P. Gibbons, M. Whit-Well, D. Cosker, T. Hemingway, J. Porter, D. Patton, S. Navia, J. Betancur, A. F. Laitenen, M. Pakarinen, K. Nieminen, J. Yla-Mononen, S. Rautiainen, S. Fiorenza, F. CA PARITY Investigators TI Prophylactic antibiotic regimens in tumour surgery (PARITY) A PILOT MULTICENTRE RANDOMISED CONTROLLED TRIAL SO BONE & JOINT RESEARCH LA English DT Article DE Orthopaedic oncology; bone sarcoma; randomised controlled trials; antibiotics; pilot study ID LIMB-SALVAGE SURGERY; QUALITY-OF-LIFE; INFECTION; OSTEOSARCOMA; AMPUTATION; REPLACEMENT; RISK AB Objective Clinical studies of patients with bone sarcomas have been challenged by insufficient numbers at individual centres to draw valid conclusions. Our objective was to assess the feasibility of conducting a definitive multi-centre randomised controlled trial (RCT) to determine whether a five-day regimen of post-operative antibiotics, in comparison to a 24-hour regimen, decreases surgical site infections in patients undergoing endoprosthetic reconstruction for lower extremity primary bone tumours. Methods We performed a pilot international multi-centre RCT. We used central randomisation to conceal treatment allocation and sham antibiotics to blind participants, surgeons, and data collectors. We determined feasibility by measuring patient enrolment, completeness of follow-up, and protocol deviations for the antibiotic regimens. Results We screened 96 patients and enrolled 60 participants (44 men and 16 women) across 21 sites from four countries over 24 months (mean 2.13 participants per site per year, standard deviation 2.14). One participant was lost to follow-up and one withdrew consent. Complete data were obtained for 98% of eligible patients at two weeks, 83% at six months, and 73% at one year (the remainder with partial data or pending queries). In total, 18 participants missed at least one dose of antibiotics or placebo post-operatively, but 93% of all postoperative doses were administered per protocol. Conclusions It is feasible to conduct a definitive multi-centre RCT of post-operative antibiotic regimens in patients with bone sarcomas, but further expansion of our collaborative network will be critical. We have demonstrated an ability to coordinate in multiple countries, enrol participants, maintain protocol adherence, and minimise losses to follow-up. C1 [Ghert, M.; Evaniew, N.; McKay, P.; Schneider, P.; Madden, K.; Scott, T.; Sprague, S.; Simunovic, N.; Swinton, M.; Racano, A.; Heels-Ansdell, D.; Buckingham, L.] McMaster Univ, Hamilton, ON L8L 8E7, Canada. [Ghert, M.; Evaniew, N.; Mckay, P.; Schneider, P.; Sobhi, G.; Chan, R.; Biljan, M.; Ghert, M.; Evaniew, N.; McKay, P.; Schneider, P.; Sobhi, G.; Chan, R.; Bil-Jan, M.] Juravinski Hosp & Canc Ctr, Hamilton, ON, Canada. [Ferguson, P.; Wunder, J.; Griffin, A.; Mantas, I.; Wylie, A.; Han, A.; Grewal, G.; Ferguson, P.; Wunder, J.; Griffin, A.; Mantas, I.; Wylie, A.; Han, A.; Grewal, G.] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Turcotte, R.; Goulding, K.; Dandachli, F.; Matte, G.; Turcotte, R.; Goulding, K.; Dandachli, F.; Matte, G.] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Werier, J.; Abdelbary, H.; Paquin, K.; Cosgrove, H.; Dugal, A-M.; Fetzer, S.; Aikens, W.; Werier, J.; Abdelbary, H.; Paquin, K.; Cosgrove, H.; Dugal, A-M.; Fetzer, S.; Aikens, W.] Ottawa Hosp, Ottawa, ON, Canada. [Clarkson, P.; Wang, B.; Kondo, L.; Yip, J.; Clarkson, P.; Wang, B.; Kondo, L.; Yip, J.] Vancouver Gen Hosp, Vancouver, BC, Canada. [Isler, M.; Mottard, S.; Barry, J.; St Yves, H.; Quach, M.; Assayag, H.; Daoust, K.; Goyette, K.; Projean, D.; Isler, M.; Mottard, S.; Barry, J.; Yves, H. St.; Quach, M.; Assayag, H.; Daoust, K.; Goyette, Kristine; Projean, D.] Hop Maison Neuve Rosemont, Montreal, PQ, Canada. [Dion, N.; Arteau, A.; Turmel, S.; Bertrand, A.; Gagnon, N.; Labbe, V.; Dion, N.; Arteau, A.; Turmel, S.; Bertrand, A.; Gagnon, N.; Labbe, V.] CHU Quebec, Quebec City, PQ, Canada. 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[Aston, W.; Pollock, R.] Royal Natl Orthopaed Hosp, Stanmore HA7 4LP, Middx, England. [Cool, P.] Robert Jones & Agnes Hunt Orthopaed Hosp, Oswestry SY10 7AG, Shrops, England. [Gibbons, M.; Whit-Well, D.; Cosker, T.; Hemingway, J.] Oxford Univ Hosp, Oxford, England. [Porter, D.; Patton, S.] Univ Edinburgh, Royal Infirm Edinburgh, Dept Surg, Edinburgh EH3 9YW, Midlothian, Scotland. [Navia, J.; Betancur, A. F.] Inst Osteoarticular Dis, Cali, Colombia. [Laitenen, M.; Pakarinen, K.; Nieminen, J.; Yla-Mononen, S.; Rautiainen, S.] Tampere Univ Hosp, Tampere, Finland. [Fiorenza, F.] Hop Dupuytren, Limoges, France. RP Ghert, M (reprint author), McMaster Univ, 293 Wellington St North,Suite 110, Hamilton, ON L8L 8E7, Canada. EM mghert@hhsc.ca RI Madden, Kim/N-5761-2015; CAMARGO, OLAVO /P-8336-2015 OI Madden, Kim/0000-0002-2861-9636; CAMARGO, OLAVO /0000-0002-1128-7292 FU Physicians' Services Incorporated; Orthopaedic Research and Education Fund/Musculoskeletal Tumor Society; Canadian Cancer Society Research Institute FX This work was supported by grants from Physicians' Services Incorporated, Orthopaedic Research and Education Fund/Musculoskeletal Tumor Society, and Canadian Cancer Society Research Institute. NR 25 TC 2 Z9 2 U1 2 U2 6 PU BRITISH EDITORIAL SOC BONE JOINT SURGERY PI LONDON PA 22 BUCKINGHAM STREET, LONDON WC2N 6ET, ENGLAND SN 2046-3758 J9 BONE JOINT RES JI Bone Jt. Res. PD SEP PY 2015 VL 4 IS 9 BP 154 EP 162 DI 10.1302/2046-3758.49.2000482 PG 9 WC Cell & Tissue Engineering; Orthopedics SC Cell Biology; Orthopedics GA CV9GU UT WOS:000364596500002 PM 26423584 ER PT J AU Farkas, MH Au, ED Sousa, ME Pierce, EA AF Farkas, Michael H. Au, Elizabeth D. Sousa, Maria E. Pierce, Eric A. TI RNA-Seq: Improving Our Understanding of Retinal Biology and Disease SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article ID DIFFERENTIAL EXPRESSION ANALYSIS; PLURIPOTENT STEM-CELLS; SPLICE JUNCTION DETECTION; GENE-EXPRESSION; RETINITIS-PIGMENTOSA; DIABETIC-RETINOPATHY; TRANSCRIPTOME ANALYSIS; MACULAR DEGENERATION; SEQUENCING DATA; SERIAL ANALYSIS AB Over the past several years, rapid technological advances have allowed for a dramatic increase in our knowledge and understanding of the transcriptional landscape, because of the ability to study gene expression in greater depth and with more detail than previously possible. To this end, RNA-Seq has quickly become one of the most widely used methods for studying transcriptomes of tissues and individual cells. Unlike previously favored analysis methods, RNA-Seq is extremely high-throughput, and is not dependent on an annotated transcriptome, laying the foundation for novel genetic discovery. Additionally, RNA-Seq derived transcriptomes provide a basis for widening the scope of research to identify potential targets in the treatment of retinal disease. C1 [Farkas, Michael H.; Au, Elizabeth D.; Sousa, Maria E.; Pierce, Eric A.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Gen Inst,Dept Ophthalmol, Boston, MA 02114 USA. RP Pierce, EA (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Gen Inst,Dept Ophthalmol, Boston, MA 02114 USA. EM eric_pierce@meei.harvard.edu OI Pierce, Eric/0000-0002-2354-4102 FU NEI NIH HHS [R01 EY020902] NR 113 TC 1 Z9 1 U1 1 U2 4 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 2157-1422 J9 CSH PERSPECT MED JI Cold Spring Harb. Perspect. Med. PD SEP PY 2015 VL 5 IS 9 AR a017152 DI 10.1101/cshperspect.a017152 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CV8KF UT WOS:000364532900001 PM 25722474 ER PT J AU Pierce, EA Bennett, J AF Pierce, Eric A. Bennett, Jean TI The Status of RPE65 Gene Therapy Trials: Safety and Efficacy SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article ID LEBER CONGENITAL AMAUROSIS; OCULAR SUBRETINAL INJECTION; RETINAL-PIGMENT EPITHELIUM; MOUSE MODEL; RETINITIS-PIGMENTOSA; ADENOASSOCIATED VIRUS; VISUAL CYCLE; CHILDHOOD BLINDNESS; RESTORES VISION; CANINE MODEL AB Several groups have reported the results of clinical trials of gene augmentation therapy for Leber congenital amaurosis (LCA) because of mutations in the RPE65 gene. These studies have used subretinal injection of adeno-associated virus (AAV) vectors to deliver the human RPE65 cDNA to the retinal pigment epithelial (RPE) cells of the treated eyes. In all of the studies reported to date, this approach has been shown to be both safe and effective. The successful clinical trials of gene augmentation therapy for retinal degeneration caused by mutations in the RPE65 gene sets the stage for broad application of gene therapy to treat retinal degenerative disorders. C1 [Pierce, Eric A.] Massachusetts Eye & Ear Infirm, Ocular Genom Inst, Dept Ophthalmol, Boston, MA 02114 USA. [Pierce, Eric A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Bennett, Jean] Univ Penn, Sch Med, FM Kirby Ctr Mol Ophthalmol, Dept Ophthalmol,Ctr Adv Retinal & Ophthalm Therap, Philadelphia, PA 19104 USA. RP Pierce, EA (reprint author), Massachusetts Eye & Ear Infirm, Ocular Genom Inst, Dept Ophthalmol, Boston, MA 02114 USA. EM eric_pierce@meei.harvard.edu; jebennet@mail.med.penn.edu OI Pierce, Eric/0000-0002-2354-4102 NR 88 TC 15 Z9 15 U1 1 U2 7 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 2157-1422 J9 CSH PERSPECT MED JI Cold Spring Harb. Perspect. Med. PD SEP PY 2015 VL 5 IS 9 AR a017285 DI 10.1101/cshperspect.a017285 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CV8KF UT WOS:000364532900002 PM 25635059 ER PT J AU LeVarge, BL Channick, RN AF LeVarge, Barbara L. Channick, Richard N. TI The changing paradigm in pulmonary hypertension trials: longer duration, new endpoints SO CURRENT OPINION IN PULMONARY MEDICINE LA English DT Review DE clinical trial design; clinical worsening; endpoints; pulmonary arterial hypertension ID ENDOTHELIN-RECEPTOR ANTAGONIST; RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; CONTINUOUS INTRAVENOUS EPOPROSTENOL; PLACEBO-CONTROLLED TRIAL; 6-MINUTE WALK DISTANCE; 5 INHIBITOR THERAPY; ARTERIAL-HYPERTENSION; DOUBLE-BLIND; ORAL TREPROSTINIL AB Purpose of reviewApproved therapies for pulmonary arterial hypertension (PAH) currently consist of 12 agents, the majority of which were approved following short-term randomized clinical trials using change in 6 minute walk distance (6MWD) as the primary outcome. However, there is growing concern that significant improvements in this measure do not translate into morbidity and mortality benefits.Recent findingsAs a result of data questioning the association between improvements in 6 minute walk distance and improvements in outcome, PAH clinical trial design is increasingly utilizing morbidity and mortality events as a composite primary outcome. This concept was recently illustrated in the published phase 3 trial of macitentan versus placebo, during which the clinical worsening event rate was decreased by 45%. Several additional unpublished trials have been similarly designed, all of which will require extended blinded treatment time in order to accrue sufficient event rates. The definition of morbidity events has varied across clinical studies; further standardization of this parameter is necessary.SummaryAlthough multiple direct and surrogate outcomes have been studied in PAH clinical research, rate of clinical worsening events, using prolonged, event-driven trial design, has emerged as the new standard. C1 [LeVarge, Barbara L.] Beth Israel Deaconess Med Ctr, Dept Pulm & Crit Care Med, Boston, MA 02215 USA. [Channick, Richard N.] Massachusetts Gen Hosp, Dept Pulm & Crit Care Med, Boston, MA 02114 USA. RP LeVarge, BL (reprint author), Beth Israel Deaconess Med Ctr, Dept Pulm & Crit Care Med, 330 Brookline Ave, Boston, MA 02215 USA. EM blevarge@bidmc.harvard.edu FU Actelion; Bayer; United Therapeutics FX R.N.C. has consulted for and received research grants from Actelion, Bayer, and United Therapeutics. NR 58 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 1070-5287 EI 1531-6971 J9 CURR OPIN PULM MED JI Curr. Opin. Pulm. Med. PD SEP PY 2015 VL 21 IS 5 BP 438 EP 445 DI 10.1097/MCP.0000000000000197 PG 8 WC Respiratory System SC Respiratory System GA CV6XM UT WOS:000364415300004 PM 26176969 ER PT J AU Commandeur, AE Styer, AK Teixeira, JM AF Commandeur, Arno E. Styer, Aaron K. Teixeira, Jose M. TI Epidemiological and genetic clues for molecular mechanisms involved in uterine leiomyoma development and growth SO HUMAN REPRODUCTION UPDATE LA English DT Article DE leiomyoma; mouse models; genetics; chromosomal rearrangements; mTOR pathway ID CATECHOL-O-METHYLTRANSFERASE; SMOOTH-MUSCLE TUMORS; LOW-DOSE MIFEPRISTONE; COMPARATIVE GENOMIC HYBRIDIZATION; RANDOMIZED CONTROLLED-TRIAL; X-CHROMOSOME INACTIVATION; HEMATOPOIETIC STEM-CELLS; MED12 EXON-2 MUTATIONS; EKER RAT MODEL; SCF-BETA-TRCP AB BACKGROUND: Uterine leiomyomas (fibroids) are highly prevalent benign smooth muscle tumors of the uterus. In the USA, the lifetime risk for women developing uterine leiomyomas is estimated as up to 75%. Except for hysterectomy, most therapies or treatments often provide only partial or temporary relief and are not successful in every patient. There is a clear racial disparity in the disease; African-American women are estimated to be three times more likely to develop uterine leiomyomas and generally develop more severe symptoms. There is also familial clustering between first-degree relatives and twins, and multiple inherited syndromes in which fibroid development occurs. Leiomyomas have been described as clonal and hormonally regulated, but despite the healthcare burden imposed by the disease, the etiology of uterine leiomyomas remains largely unknown. The mechanisms involved in their growth are also essentially unknown, which has contributed to the slow progress in development of effective treatment options. METHODS: A comprehensive PubMed search for and critical assessment of articles related to the epidemiological, biological and genetic clues for uterine leiomyoma development was performed. The individual functions of some of the best candidate genes are explained to provide more insight into their biological function and to interconnect and organize genes and pathways in one overarching figure that represents the current state of knowledge about uterine leiomyoma development and growth. RESULTS: In this review, the widely recognized roles of estrogen and progesterone in uterine leiomyoma pathobiology on the basis of clinical and experimental data are presented. This is followed by fundamental aspects and concepts including the possible cellular origin of uterine fibroids. The central themes in the subsequent parts are cytogenetic aberrations in leiomyomas and the racial/ethnic disparities in uterine fibroid biology. Then, the attributes of various in vitro and in vivo, human syndrome, rodent xenograft, naturally mutant, and genetically modified models used to study possible molecular mechanisms of leiomyoma development and growth are described. Particular emphasis is placed on known links to fibrosis, hypertrophy, and hyperplasia and genes that are potentially important in these processes. CONCLUSIONS: Menstrual cycle-related injury and repair and coinciding hormonal cycling appears to affect myometrial stem cells that, at a certain stage of fibroid development, often obtain cytogenetic aberrations and mutations of Mediator complex subunit 12 (MED12). Mammalian target of rapamycin (mTOR), a master regulator of proliferation, is activated in many of these tumors, possibly by mechanisms that are similar to some human fibrosis syndromes and/or by mutation of upstream tumor suppressor genes. Animal models of the disease support some of these dysregulated pathways in fibroid etiology or pathogenesis, but none are definitive. All of this suggests that there are likely several key mechanisms involved in the disease that, in addition to increasing the complexity of uterine fibroid pathobiology, offer possible approaches for patient-specific therapies. A final model that incorporates many of these reported mechanisms is presented with a discussion of their implications for leiomyoma clinical practice. C1 [Commandeur, Arno E.] Univ Amsterdam, Acad Med Ctr, Womens & Childrens Hosp, Ctr Reprod Med, NL-1105 AZ Amsterdam, Netherlands. [Styer, Aaron K.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Massachusetts Gen Hosp,Vincent Ctr Reprod Biol, Boston, MA 02115 USA. [Teixeira, Jose M.] Michigan State Univ, Coll Human Med, Dept Obstet Gynecol & Reprod Biol, Grand Rapids, MI 49503 USA. [Teixeira, Jose M.] Spectrum Hlth Syst, Dept Womens Hlth, Grand Rapids, MI USA. RP Teixeira, JM (reprint author), Michigan State Univ, Coll Human Med, Dept Obstet Gynecol & Reprod Biol, 333 Bostwick Ave NE,4018A, Grand Rapids, MI 49503 USA. EM jose.teixeira@hc.msu.edu OI Teixeira, Jose/0000-0002-6438-5064 FU National Institutes of Health [R01OD012206, R01HD072489]; Office of Diversity Inclusion and Community Partnership/Harvard Catalyst Faculty Fellowship, Harvard Medical School; Academic Medical Center (AMC) PhD Scholarship FX This worked was funded by: National Institutes of Health Grants R01OD012206 and R01HD072489 (J.M.T.); and Office of Diversity Inclusion and Community Partnership/Harvard Catalyst Faculty Fellowship, Harvard Medical School (A.K.S.). A.E.C. is the recipient of an Academic Medical Center (AMC) PhD Scholarship. NR 287 TC 9 Z9 10 U1 4 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1355-4786 EI 1460-2369 J9 HUM REPROD UPDATE JI Hum. Reprod. Update PD SEP-OCT PY 2015 VL 21 IS 5 BP 593 EP 615 DI 10.1093/humupd/dmv030 PG 23 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CV5SK UT WOS:000364331200004 PM 26141720 ER PT J AU Radulovic, M Bauman, WA Wecht, JM LaFountaine, M Kahn, N Hobson, J Singh, K Renzi, C Yen, C Schilero, GJ AF Radulovic, Miroslav Bauman, William A. Wecht, Jill M. LaFountaine, Michael Kahn, Nighat Hobson, Joshua Singh, Kamaldeep Renzi, Christopher Yen, Christina Schilero, Gregory J. TI Biomarkers of inflammation in persons with chronic tetraplegia SO JOURNAL OF BREATH RESEARCH LA English DT Article DE spinal cord injury; tetraplegia; oxidative stress; asthma ID EXHALED BREATH CONDENSATE; SPINAL-CORD-INJURY; OBSTRUCTIVE PULMONARY-DISEASE; NITRIC-OXIDE MEASUREMENTS; AIR-FLOW OBSTRUCTION; OXIDATIVE STRESS; ASTHMA CONTROL; BRONCHIAL HYPERRESPONSIVENESS; INDUCED BRONCHOCONSTRICTION; INCREASED 8-ISOPROSTANE AB In addition to lung volume restriction, individuals with chronic tetraplegia exhibit reduced airway caliber and bronchodilator responsiveness similar to persons with asthma. In asthma, airflow obstruction is closely linked to airway inflammation. Conversely, little is known regarding the airway inflammatory response in tetraplegia. To compare levels of biomarkers of inflammation in exhaled breath condensate (EBC) and serum in subjects with chronic tetraplegia, mild asthma, and able-bodied controls. Prospective, observational pilot study. Thirty-four subjects participated: tetraplegia (n = 12), asthma (n = 12), controls (n = 10). Biomarkers in EBC [8-isoprostane (8-IP), leukotriene B4 (LT-B4), prostaglandin E2 (PG-E2), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6)] and serum (8-IP, LT-B4, TNF-a, IL-6) were determined using commercially available EIA kits (Cayman Chemical Company, Ann Arbor, MI). Separate, one-way ANOVA with Bonferroni's post-hoc analyses were performed to determine group differences in demographic and dependent variables [EBC and serum biomarkers, fractional exhaled nitric oxide (FeNO), pulmonary function parameters, and specific airway conductance (sGaw)]. The tetraplegia group had significantly elevated 8-IP levels in EBC compared to the asthma (68 +/- 38 versus 21 +/- 13 pg ml(-1); p < 0.001) and control groups (22 +/- 13 pg ml(-1); p < 0.01), respectively. FeNO levels were significantly elevated in the asthma compared to the control group (26 +/- 18 versus 11 +/- 4 ppb; p < 0.05), and trended higher than levels in the tetraplegia group (15 +/- 6; p = 0.08). Levels of serum biomarkers did not differ significantly among groups. Through analysis of EBC, levels of 8-IP were significantly elevated compared to levels found in individuals with mild asthma and healthy controls. Further studies are needed to extend upon these preliminary findings that suggest the presence of airway inflammation in subjects with chronic tetraplegia, and how this relates to pulmonary dysfunction in this population. C1 [Radulovic, Miroslav; Bauman, William A.; Wecht, Jill M.; LaFountaine, Michael; Kahn, Nighat; Hobson, Joshua; Singh, Kamaldeep; Renzi, Christopher; Yen, Christina; Schilero, Gregory J.] James J Peters VA Med Ctr, Rehabil Res & Dev Ctr Excellence Med Consequences, Bronx, NY 10468 USA. [Radulovic, Miroslav; Bauman, William A.; Wecht, Jill M.; Schilero, Gregory J.] James J Peters VA Med Ctr, Med Serv, Bronx, NY 10468 USA. [Radulovic, Miroslav; Bauman, William A.; Wecht, Jill M.; Schilero, Gregory J.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Bauman, William A.; Wecht, Jill M.] Icahn Sch Med Mt Sinai, Dept Rehabil Med, New York, NY 10029 USA. RP Radulovic, M (reprint author), James J Peters VA Med Ctr, Rehabil Res & Dev Ctr Excellence Med Consequences, Bronx, NY 10468 USA. EM Miroslav.Radulovic@va.gov FU Veteran Affairs Rehabilitation Research and Development Service [B6623R, B4335V, B4162C]; James J Peters VA Medical Center FX This research was supported by the Veteran Affairs Rehabilitation Research and Development Service (#B6623R, #B4335V, #B4162C) and the James J Peters VA Medical Center. NR 69 TC 0 Z9 0 U1 2 U2 3 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1752-7155 EI 1752-7163 J9 J BREATH RES JI J. Breath Res. PD SEP PY 2015 VL 9 IS 3 AR 036001 DI 10.1088/1752-7155/9/3/036001 PG 9 WC Biochemical Research Methods; Respiratory System SC Biochemistry & Molecular Biology; Respiratory System GA CW1YY UT WOS:000364789300004 PM 25971935 ER PT J AU Jao, J Kirmse, B Yu, CL Qiu, YP Powis, K Nshom, E Epie, F Tih, PM Sperling, RS Abrams, EJ Geffner, ME LeRoith, D Kurland, IJ AF Jao, Jennifer Kirmse, Brian Yu, Chunli Qiu, Yunping Powis, Kathleen Nshom, Emmanuel Epie, Fanny Tih, Pius Muffih Sperling, Rhoda S. Abrams, Elaine J. Geffner, Mitchell E. LeRoith, Derek Kurland, Irwin J. TI Lower Preprandial Insulin and Altered Fuel Use in HIV/Antiretroviral-Exposed Infants in Cameroon SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FOR-GESTATIONAL-AGE; DNA POLYMERASE-GAMMA; MITOCHONDRIAL DYSFUNCTION; BIRTH-WEIGHT; AMINO-ACIDS; RESISTANCE; CHILDREN; GLUCOSE; TERM; ACYLCARNITINES AB Context: Intrauterine HIV/antiretroviral (ARV) and postnatal ARVs are known to perturb energy metabolism and could have permanent effects on future metabolic health. Such maladaptive effects could be mediated by changes in mitochondrial function and intermediary metabolism due to fetal and early-life ARV exposure in HIV/ARV-exposed uninfected (NEU) infants. Objective:The objective of the study vvasto understand the relationship(s) between mitochondrial fuel use (assessed via acylcarnitines and branched chain amino acids) and preprandial insulin in infants exposed to in utero HIV/ARV plus postnatal zidovudine or nevirapine compared with HIV/ ARV-unexposed uninfected (HUU) infants. Design: This was a prospective cohort study with the following three groups: 1) intrauterine HIV/ ARV/postnatal zidovudine-exposed (HEU-A), 2) intrauterine HIV/ARV/postnatal nevirapine-exposed (HEU-N), and 3) HUU infants. Principal component analysis and linear regression modeling were performed to assess the association between in utero HIV/ARV exposure and infant insulin. Setting: The study was conducted at Cameroonian urban antenatal centers. Participants: HIV-infected and -uninfected pregnant woman/infant dyads participated in the study. Main Outcome: Preprandial insulin was the main outcome measured. Results: Of 366 infants, 38 were HEU-A, 118 HEU-N. Forty intermediary metabolites were consolidated into seven principal components. In a multivariate analysis, both HEU-A (p =.116, P=.012) and HEU-N (p =.070, P=.022) demonstrated lower insulin compared with HUU infants. However, at high levels of plasma metabolites, HEU-A (13 =.027, P=.050) exhibited higher insulin levels than HEU-N or HUU infants. A unique array of short-chain acylcarnitines ([3 =.044, P=.001) and branched-chain amino acids (p =.033, P=.012) was associated with insulin. Conclusion: HEU-A and HEU-N infants have lower preprandial insulin levels at 6 weeks of age and appear to use metabolic fuel substrates differently than HUU infants. Futurestudies are warranted to determine whether observed differences have lasting metabolic implications, such as later insulin resistance. C1 [Jao, Jennifer] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Jao, Jennifer; Sperling, Rhoda S.] Icahn Sch Med Mt Sinai, Dept Obstet Gynecol & Reprod Sci, New York, NY 10029 USA. [Yu, Chunli] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [LeRoith, Derek] Icahn Sch Med Mt Sinai, Dept Med, Div Endocrinol, New York, NY 10029 USA. [Kirmse, Brian] George Washington Univ, Sch Med, Childrens Natl Med Ctr, Dept Pediat,Div Genet & Metab, Washington, DC 20037 USA. [Qiu, Yunping; Kurland, Irwin J.] Albert Einstein Coll Med, Dept Med, Div Endocrinol, Bronx, NY 10461 USA. [Powis, Kathleen] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Powis, Kathleen] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Nshom, Emmanuel; Epie, Fanny; Tih, Pius Muffih] Cameroon Baptist Convent Hlth Serv, Bamenda, Cameroon. [Abrams, Elaine J.] Columbia Univ, Mailman Sch Publ Hlth, ICAP, New York, NY 10032 USA. [Abrams, Elaine J.] Columbia Univ, Coll Phys & Surg, New York, NY 10032 USA. [Geffner, Mitchell E.] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Saban Res Inst, Los Angeles, CA 90033 USA. RP Jao, J (reprint author), Icahn Sch Med Mt Sinai, Dept Med, One Gustave L Levy Pl,Box 1087, New York, NY 10029 USA. EM jennifer.jao@mssm.edu OI Qiu, Yunping/0000-0003-1039-5264 FU Icahn School of Medicine at Mount Sinai Global Health Innovation Fund; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [K23HD070760]; National Institutes of Health National Center for Advancing Translational Sciences [KL2TR000076]; NICHD [K23HD070774]; National Institute of Diabetes and Digestive and Kidney Diseases [P60DK020541]; NICHD; National Institute of Allergy and Infectious Diseases [1U19AI091175]; National Institute on Drug Abuse; National Institute of Mental Health; National Institute on Deafness and Other Communication Disorders; National Heart, Lung, and Blood Institute; National Institute of Neurological Disorders and Stroke; National Institute on Alcohol Abuse and Alcoholism [U01 HD052102-04]; Tulane University School of Medicine [U01 HD052104-01] FX This work was supported by the Icahn School of Medicine at Mount Sinai Global Health Innovation Fund. J.J. is supported by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Grant K23HD070760. B.K. was supported by Grant KL2TR000076 from the National Institutes of Health National Center for Advancing Translational Sciences during the preparation of this manuscript. K.P. is supported by NICHD Grant K23HD070774. Y.Q. is supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant P60DK020541. M.G. is partially supported by the Pediatric HIV/AIDS Cohort Study, which is supported by the NICHD with cofunding from the National Institute of Allergy and Infectious Diseases, the National Institute on Drug Abuse, the National Institute of Mental Health, the National Institute on Deafness and Other Communication Disorders, the National Heart, Lung, and Blood Institute, the National Institute of Neurological Disorders and Stroke, and the National institute on Alcohol Abuse and Alcoholism, through cooperative agreements with the I laniard University School of Public Health (Grant U01 HD052102-04) and the Tulane University School of Medicine (Grant U01 HD052104-01). I.J.K. is supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant P60DK020541 (Einstein Diabetes Research and Training Center) and National Institute of Allergy and Infectious Diseases Grant 1U19AI091175 (Einstein Center for Medical Countermeasures against Radiation). NR 40 TC 4 Z9 4 U1 1 U2 2 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 SEP PY 2015 VL 100 IS 9 BP 3260 EP 3269 DI 10.1210/jc.2015-2198 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CW3BV UT WOS:000364867800030 PM 26133363 ER PT J AU Carhill, AA Litofsky, DR Ross, DS Jonklaas, J Cooper, DS Brierley, JD Ladenson, PW Ain, KB Fein, HG Haugen, BR Magner, J Skarulis, MC Steward, DL Xing, MX Maxon, HR Sherman, SI AF Carhill, Aubrey A. Litofsky, Danielle R. Ross, Douglas S. Jonklaas, Jacqueline Cooper, David S. Brierley, James D. Ladenson, Paul W. Ain, Kenneth B. Fein, Henry G. Haugen, Bryan R. Magner, James Skarulis, Monica C. Steward, David L. Xing, Mingxhao Maxon, Harry R. Sherman, Steven I. TI Long-Term Outcomes Following Therapy in Differentiated Thyroid Carcinoma: NTCTCS Registry Analysis 1987-2012 SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID THYROTROPIN-SUPPRESSIVE THERAPY; QUALITY-OF-LIFE; SERUM THYROTROPIN; STIMULATING HORMONE; EXERCISE CAPACITY; INITIAL THERAPY; RISK PAPILLARY; CANCER; DISEASE; LEVOTHYROXINE AB Context: Initial treatments for patients with differentiated thyroid cancer are supported primarily by single-institution, retrospective studies, with limited follow-up and low event rates. We report updated analyses of long-term outcomes after treatment in patients with differentiated thyroid cancer. Objective: The objective was to examine effects of initial therapies on outcomes. Design/Setting: This was a prospective multi-institutional registry. Patients: A total of 4941 patients, median follow-up, 6 years, participated. Intervention: Interventions included total/near-total thyroidectomy (T/NTT), postoperative radioiodine (RAI), and thyroid hormone suppression therapy (THST). Main Outcome Measure: Main outcome measures were overall survival (OS) and disease-free survival using product limit and proportional hazards analyses. Results: Improved OS was noted in NTCTCS stage III patients who received RAI (risk ratio [RR], 0.66; P =.04) and stage IV patients who received both T/NTT and RAI (RR, 0.66 and 0.70; combined P =.049). In all stages, moderate THST (TSH maintained subnormal-normal) was associated with significantly improved OS (RR stages I-IV: 0.13, 0.09, 0.13, 0.33) and disease-free survival (RR stages I-III: 0.52, 0.40, 0.18); no additional survival benefit was achieved with more aggressive THST (TSH maintained undetectable-subnormal). This remained true, even when distant metastatic disease was diagnosed during follow-up. Lower initial stage and moderate THST were independent predictors of improved OS during follow-up years 1-3. Conclusions: We confirm previous findings that T/NTT followed by RAI is associated with benefit in high-risk patients, but not in low-risk patients. In contrast with earlier reports, moderate THST is associated with better outcomes across all stages, and aggressive THST may not be warranted even in patients diagnosed with distant metastatic disease during follow-up. Moderate THST continued at least 3 years after diagnosis may be indicated in high-risk patients. C1 [Carhill, Aubrey A.; Litofsky, Danielle R.; Sherman, Steven I.] Univ Texas MD Anderson Canc Ctr, Dept Endocrine Neoplasia & Hormonal Disorders, Houston, TX 77030 USA. [Litofsky, Danielle R.] Massachusetts Gen Hosp, Thyroid Unit, Boston, MA 02114 USA. [Jonklaas, Jacqueline] Georgetown Univ, Med Ctr, Dept Med, Div Endocrinol, Washington, DC 20057 USA. [Cooper, David S.; Ladenson, Paul W.; Xing, Mingxhao] Johns Hopkins Univ, Sch Med, Div Endocrinol & Metab, Baltimore, MD 21205 USA. [Brierley, James D.] Princess Margaret Hosp, Dept Radiat Oncol, Toronto, ON M5G 2M9, Canada. [Ain, Kenneth B.] Vet Affairs Med Ctr, Dept Internal Med, Lexington, KY 40502 USA. [Ain, Kenneth B.] Univ Kentucky, Lexington, KY 40502 USA. [Fein, Henry G.] Sinai Hosp, Div Endocrinol & Metab, Baltimore, MD 21215 USA. [Haugen, Bryan R.] Univ Colorado, Sch Med, Div Endocrinol Metab & Diabet, Aurora, CO 80045 USA. [Magner, James] Genzyme, Cambridge, MA 02142 USA. [Skarulis, Monica C.] NIH, Diabet, Endocrinol, Obes Branch, Bethesda, MD 20892 USA. [Steward, David L.] Univ Cincinnati, Med Ctr, Dept Head & Neck Surg, Cincinnati, OH 45219 USA. [Maxon, Harry R.] Univ Cincinnati, Med Ctr, Dept Nucl Med, Cincinnati, OH 45219 USA. RP Sherman, SI (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Endocrine Neoplasia & Hormonal Disorders, 1400 Pressler,Unit 1461, Houston, TX 77030 USA. EM sisherma@mdanderson.org OI Sherman, Steven/0000-0002-3079-5153 FU Genzyme, a Sanofi company; Pfizer; University of Texas MD Anderson Cancer Center Support Grant (NCI) [P30 CA016672] FX The NTCTCS has been supported in part by research grants from Genzyme, a Sanofi company, and Pfizer, and by the University of Texas MD Anderson Cancer Center Support Grant (NCI Grant P30 CA016672). NR 40 TC 5 Z9 7 U1 0 U2 4 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 SEP PY 2015 VL 100 IS 9 BP 3270 EP 3279 DI 10.1210/JC.2015-1346 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CW3BV UT WOS:000364867800031 PM 26171797 ER PT J AU Swerdloff, RS Pak, Y Wang, C Liu, PY Bhasin, S Gill, TM Matsumoto, AM Pahor, M Surampudi, P Snyder, PJ AF Swerdloff, Ronald S. Pak, Youngju Wang, Christina Liu, Peter Y. Bhasin, Shalender Gill, Thomas M. Matsumoto, Alvin M. Pahor, Marco Surampudi, Prasanth Snyder, Peter J. TI Serum Testosterone (T) Level Variability in T Gel-Treated Older Hypogonadal Men: Treatment Monitoring Implications SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID METABOLIC-CLEARANCE; MASS-SPECTROMETRY; BODY-COMPOSITION; ELDERLY-MEN; METAANALYSIS; THERAPY; EVENTS; TRIALS; PHARMACOKINETICS; MORTALITY AB Context: The optimal frequency for on-treatment serum T measurement used for dose adjustment aftertransdermal T gel application is unknown, especially in older men withthinner skin and slower metabolic clearance. Objectives: The objectives of the study was to determine the variability of postgel application serum T concentrations and assess whether single levels are reflective of average serum T concentrations over 24 hours (Cavg(0-24)). Design: This was a double-blinded, placebo-controlled randomized trial. Setting: The study was conducted at five academic centers. Participants: Forty-seven symptomatic men 65 years old or older with an average of two morning T concentration less than 275 ng/dL participated in the study. Intervention(s): Transdermal T or placebo gel was applied for 120 +/- 14 days. Monthly dose adjustments were made if necessary to target serum T between 400 and 500 to 800 ng/dL. Main Outcome Measures: Variability of serum 12 hours afterthe gel application on two outpatient visits and at multiple time points over 24 hours during the inpatient day was measured. Results: On-treatment T levels varied substantially on the 2 ambulatory days and over 24 hours during the inpatient day. Ambulatory 2-hour postapplication T levels did not correlate significantly with either 2-hour postapplication serum T or Cavg(0-24) measured during the inpatient day. Only 22.2% of men receiving T had a Cavg(0-24) within the target range of 500-800 ng/dL; 81.5% had a Cavg0_24 within the broader 300-1000 ng/dL range. Conclusion: Large within-individual variations in serum T after T gel application render ambulatory 2-hour postapplication T level a poor indicator of average serum Ton another day. Our data point out the limitations of dose adjustments based on a single postapplication serum T measurement. C1 [Swerdloff, Ronald S.; Pak, Youngju; Wang, Christina; Liu, Peter Y.; Surampudi, Prasanth] Harbor UCLA Med Ctr, Dept Med, Div Endocrinol, Torrance, CA 90509 USA. [Pak, Youngju; Wang, Christina] Harbor UCLA Med Ctr, Clin & Translat Sci Inst, Torrance, CA 90509 USA. Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Bhasin, Shalender] Harvard Univ, Sch Med, Brigham & Womens Hosp, Res Program Mens Hlth Aging & Metab, Boston, MA 02115 USA. [Gill, Thomas M.] Yale Univ, New Haven, CT 06510 USA. [Matsumoto, Alvin M.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98108 USA. [Matsumoto, Alvin M.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Clin, Seattle, WA 98108 USA. [Pahor, Marco] Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL 32611 USA. [Snyder, Peter J.] Univ Penn, Dept Med, Div Endocrinol, Philadelphia, PA 19104 USA. RP Swerdloff, RS (reprint author), Harbor UCLA Med Ctr, Dept Med, Div Endocrinol, Walter Martin Res Bldg,1000 Carson St, Torrance, CA 90509 USA. EM swerdloff@labiomed.org FU National Institute on Aging, National Institutes of Health [U01 AG030644]; National Heart, Lung, and Blood Institute, National Institute of Neurological Diseases and Stroke, and Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Center for Advancing Translational Sciences through University of California, Los Angeles, Clinical and Translational Science Institute [UL1TR000124]; Diabetes and Endocrinology Training Grant [T32 DK007571]; Department of Veterans Affairs Puget Sound Health Care System; National Institute on Aging [K07AG3587]; Claude D. Pepper Older Americans Independence Center [P30-AG021342]; Clinical and Translational Science Institute [UL1TR000142]; Boston Claude D. Pepper Older Americans Independence Center Grant [5P30AG031679]; Clinical and Translational Science Institute from Boston University [1 UL1RR025771] FX The testosterone trials were supported by a grant the National Institute on Aging, National Institutes of Health (Grant U01 AG030644), supplemented by support from the National Heart, Lung, and Blood Institute, National Institute of Neurological Diseases and Stroke, and Eunice Kennedy Shriver National Institute of Child Health and Human Development. AbbVie (formerly Solvay and Abbott Laboratories) generously provided support and donated the AndroGel and placebo gel.; This work was supported by the National Center for Advancing Translational Sciences through the University of California, Los Angeles, Clinical and Translational Science Institute (Grant UL1TR000124) and Diabetes and Endocrinology Training Grant T32 DK007571 to the Los Angeles site). A.M.M. is supported by the Department of Veterans Affairs Puget Sound Health Care System. T.M.G. was the recipient of Academic Leadership Award K07AG3587 from the National Institute on Aging. the Yale Field Center was partially supported by the Claude D. Pepper Older Americans Independence Center (Grant P30-AG021342) and Clinical and Translational Science Institute Grant UL1TR000142. Additional support was provided by resources of the Boston Claude D. Pepper Older Americans Independence Center Grant 5P30AG031679 (to S.B.) and Clinical and Translational Science Institute Grant 1 UL1RR025771 from Boston University. NR 21 TC 6 Z9 6 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 SEP PY 2015 VL 100 IS 9 BP 3280 EP 3287 DI 10.1210/JC.2015-1542 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CW3BV UT WOS:000364867800032 PM 26120790 ER PT J AU Schorr, M Lawson, EA Dichtel, LE Klibanski, A Miller, KK AF Schorr, Melanie Lawson, Elizabeth A. Dichtel, Laura E. Klibanski, Anne Miller, Karen K. TI Cortisol Measures Across the Weight Spectrum SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BODY-MASS INDEX; X-RAY ABSORPTIOMETRY; PITUITARY-ADRENAL-FUNCTION; BONE-MINERAL DENSITY; ANOREXIA-NERVOSA; CUSHINGS-SYNDROME; PLASMA-CORTISOL; OBESE WOMEN; POSTMENOPAUSAL WOMEN; METABOLIC SYNDROME AB Context: There are conflicting reports of increased vs decreased hypothalamic-pituitary-adrenal (HPA) activation in obesity; the most consistent finding is an inverse relationship between body mass index (BMI) and morning cortisol. In anorexia nervosa (AN), a low-BMI state, cortisol measures are elevated. Objective: This study aimed to investigate cortisol measures across the weight spectrum. Design and Setting: This was a cross-sectional study at a clinical research center. Participants: This study included 60 women, 18-45 years of age: overweight/obese (OB; N = 21); AN (N = 18); and normal-weight controls (HC; N = 21). Measures: HPA dynamics were assessed by urinary free cortisol, mean overnight serum cortisol obtained by pooled frequent sampling every 20 minutes from 2000-0800 h, 0800 h serum cortisol and cortisol-binding globulin, morning and late-night salivary cortisol, and dexamethasone-CRH testing. Body composition and bone mineral density (BMD) were assessed by dual-energy x-ray absorptiometry. Results: Cortisol measures demonstrated a U-shaped relationship with BMI, nadiring in the overweight-class I obese range, and were similarly associated with visceral adipose tissue and total fat mass. Mean cortisol levels were higher in AN than OB. There were weak negative linear relationships between lean mass and some cortisol measures. Most cortisol measures were negatively associated with postero-anterior spine and total hip BMD. Conclusions: Cortisol measures are lowest in overweight-class I obese women lower than in lean women. With more significant obesity, cortisol levels increase, although not to as high as in AN. Therefore, extreme underweight and overweight states may activate the HPA axis, and hypercortisolemia may contribute to increased adiposity in the setting of caloric excess. Hypercortisolemia may also contribute to decreased BMD and muscle wasting in the setting of both caloric restriction and excess. C1 [Miller, Karen K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Miller, KK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St,Bulfinch 457B, Boston, MA 02114 USA. EM KKMiller@mgh.harvard.edu FU National Institutes of Health [K24 HL092902, T32 DK007028, R01 DK052625, UL1 RR025758] FX This work was supported by National Institutes of Health Grants K24 HL092902, T32 DK007028, R01 DK052625, and UL1 RR025758. NR 42 TC 9 Z9 9 U1 1 U2 4 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 SEP PY 2015 VL 100 IS 9 BP 3313 EP 3321 DI 10.1210/JC.2015-2078 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CW3BV UT WOS:000364867800036 PM 26171799 ER PT J AU Shaw, ND Srouji, SS Welt, CK Cox, KH Fox, JH Adams, JA Sluss, PM Hall, JE AF Shaw, N. D. Srouji, S. S. Welt, C. K. Cox, K. H. Fox, J. H. Adams, J. A. Sluss, P. M. Hall, J. E. TI Compensatory Increase in Ovarian Aromatase in Older Regularly Cycling Women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; ANTI-MULLERIAN HORMONE; AGE-RELATED-CHANGES; ADVANCED REPRODUCTIVE AGE; EPIDERMAL-GROWTH-FACTOR; HUMAN GRANULOSA-CELLS; MESSENGER-RNA; LUTEINIZING-HORMONE; INHIBIN-B; GENE-EXPRESSION AB Context: Serum estradiol (E2) levels are preserved in older reproductive-aged women with regular menstrual cycles despite declining ovarian function. Objective:The objective of the study was to determine whether increased granulosa cell aromatase expression and activity account for preservation of E2 levels in older, regularly cycling women. Design: The protocol included daily blood sampling and dominant follicle aspirations at an academic medical center during a natural menstrual cycle. Subjects: Healthy, regularly cycling older (36-45 y; n=13) and younger (22-34 y; n = 14) women participated in the study. Main Outcome Measures: Hormone levels were measured in peripheral blood and follicular fluid aspirates and granulosa cell CYP19A1 (aromatase) and FSH-R mRNA expression were determined. Results: Older women had higher FSH levels than younger women during the early follicular phase with similar E2 but lower inhibin B and antimullerian hormone levels. Late follicular phase serum E2 did not differ between the two groups. Follicular fluid E2 [older (O) = 960.0 [interguartile range (IQR) 765.0-1419.0]; younger (Y) = 994.5 [647.3-1426.5] ng/mL, P = 1.0], estrone (O = 39.6 [29.5 - 54.1]; Y = 28.8 [22.5-42.1] ng/mL, P = 0.3), and the E2 to testosterone (T) ratio (O = 109.0 +/- 41.9; Y = 83.0 +/- 18.6, P = .50) were preserved in older women. Granulosa cell CYP19A1 expression was increased 3-fold in older compared with younger women (P <.001), with no difference in FSH-R expression. Conclusions: Ovarian aromatase expression increases with age in regularly cycling women. Thus, up-regulation of aromatase activity appears to compensate for the known age-related decrease in granulosa cell number in the dominant follicle to maintain ovarian estrogen production in older premenopausal women. C1 [Shaw, N. D.; Srouji, S. S.; Welt, C. K.; Cox, K. H.; Adams, J. A.; Sluss, P. M.; Hall, J. E.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. [Shaw, N. D.] Brigham & Womens Hosp, Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Srouji, S. S.; Fox, J. H.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Ctr Infertil & Reprod Surg, Boston, MA 02115 USA. RP Hall, JE (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX-5,55 Fruit St, Boston, MA 02114 USA. EM jehall@partners.org RI Cox, Kimberly/P-1931-2016; OI Cox, Kimberly/0000-0002-7097-9563; Welt, Corrine/0000-0002-8219-5504; Shaw, Natalie/0000-0002-0847-9170; Hall, Janet/0000-0003-4644-3061 FU National Institutes of Health [R01HD 42708, M01 RR01066, 5T32 HD007396, 1K23 HD073304-01]; Clinical Science program of Harvard Catalyst [The Harvard Clinical and Translational Science Center] [UL1 RR 025758]; Clinical Science program of Harvard Catalyst [Harvard University]; Clinical Science program of Harvard Catalyst [academic health care centers] FX This work was supported by National Institutes of Health Grants R01HD 42708 and M01 RR01066. N.D.S. received fellowship support from the National Institutes of Health (Grants 5T32 HD007396 and 1K23 HD073304-01) and from the Scholars in Clinical Science program of Harvard Catalyst [The Harvard Clinical and Translational Science Center (Award UL1 RR 025758) and financial contributions from Harvard University and its affiliated academic health care centers]. NR 62 TC 0 Z9 0 U1 1 U2 2 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 SEP PY 2015 VL 100 IS 9 BP 3539 EP 3547 DI 10.1210/JC.2015-2191 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CW3BV UT WOS:000364867800063 PM 26126208 ER PT J AU Shelton, E Allegretti, J Stevens, B Lucci, M Ananthakrishnan, A Yajnik, V AF Shelton, E. Allegretti, J. Stevens, B. Lucci, M. Ananthakrishnan, A. Yajnik, V. TI Efficacy of vedolizumab as induction therapy in refractory IBD patients: a multicentre cohort SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Meeting Abstract C1 [Shelton, E.; Stevens, B.; Ananthakrishnan, A.; Yajnik, V.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Shelton, E.; Allegretti, J.; Ananthakrishnan, A.; Yajnik, V.] Harvard Univ, Sch Med, Boston, MA USA. [Allegretti, J.; Lucci, M.] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0815-9319 EI 1440-1746 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD SEP PY 2015 VL 30 SU 3 SI SI BP 138 EP 139 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CV8CZ UT WOS:000364505900269 ER PT J AU Selleck, EM Orchard, RC Lassen, KG Beatty, WL Xavier, RJ Levine, B Virgin, HW Sibley, LD AF Selleck, Elizabeth M. Orchard, Robert C. Lassen, Kara G. Beatty, Wandy L. Xavier, Ramnik J. Levine, Beth Virgin, Herbert W. Sibley, L. David TI A Noncanonical Autophagy Pathway Restricts Toxoplasma gondii Growth in a Strain-Specific Manner in IFN-gamma-Activated Human Cells SO MBIO LA English DT Article ID PARASITOPHOROUS VACUOLE MEMBRANE; HUMAN-FIBROBLASTS; PLASMA-MEMBRANE; ACUTE VIRULENCE; IMMUNITY; PROTEINS; INFECTION; INVASION; BACTERIA; GTPASES AB A core set of autophagy proteins is required for gamma interferon (IFN-gamma)-mediated clearance of Toxoplasma gondii in the mouse because of their control of several downstream effectors, including immunity-related GTPases (IRGs) and guanylate-binding proteins (GBPs). However, these effectors are absent (i.e., IRGs) from or nonessential (i.e., GBPs) in IFN-gamma-activated human cells, raising the question of how these cells control parasite replication. Here, we define a novel role for ubiquitination and recruitment of autophagy adaptors in the strain-specific control of T. gondii replication in IFN-gamma-activated human cells. Vacuoles containing susceptible strains of T. gondii became ubiquitinated, recruited the adaptors p62 and NDP52, and were decorated with LC3. Parasites within LC3-positive vacuoles became enclosed in multiple layers of host membranes, resulting in stunting of parasite replication. However, LC3-positive T. gondii-containing vacuoles did not fuse with endosomes and lysosomes, indicating that this process is fundamentally different from xenophagy, a form of autophagy involved in the control of intracellular bacterial pathogens. Genetic knockout of ATG16L or ATG7 reverted the membrane encapsulation and restored parasite replication, indicating that core autophagy proteins involved in LC3 conjugation are important in the control of parasite growth. Despite a role for the core autophagy machinery in this process, upstream activation through Beclin 1 was not sufficient to enhance the ubiquitination of T. gondii-containing vacuoles, suggesting a lack of reliance on canonical autophagy. These findings demonstrate a new mechanism for IFN-gamma-dependent control of T. gondii in human cells that depends on ubiquitination and core autophagy proteins that mediate membrane engulfment and restricted growth. IMPORTANCE Autophagy is a process of cellular remodeling that allows the cell to recycle senescent organelles and recapture nutrients. During innate immune responses in the mouse, autophagy is recruited to help target intracellular pathogens and thus eliminate them. However, the antimicrobial mediators that depend on autophagy in the mouse are not conserved in humans, raising the issue of how human cells control intracellular pathogens. Our study defines a new pathway for the control of the ubiquitous intracellular parasite T. gondii in human cells activated by IFN-gamma. Recruitment of autophagy adaptors resulted in engulfment of the parasite in multiple membranes and growth impairment. Although susceptible type 2 and 3 stains of T. gondii were captured by this autophagy-dependent pathway, type 1 strains were able to avoid entrapment. C1 [Selleck, Elizabeth M.; Beatty, Wandy L.; Sibley, L. David] Washington Univ, Sch Med, Dept Mol Immunol, St Louis, MO 63130 USA. [Orchard, Robert C.; Virgin, Herbert W.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Lassen, Kara G.; Xavier, Ramnik J.] Bread Inst MIT & Harvard, Cambridge, MA USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Levine, Beth] Univ Texas SW Med Ctr Dallas, Ctr Autophagy Res, Dept Microbiol, Dept Internal Med, Dallas, TX 75390 USA. [Levine, Beth] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA. RP Sibley, LD (reprint author), Washington Univ, Sch Med, Dept Mol Immunol, St Louis, MO 63130 USA. EM sibley@wusm.wustl.edu OI Selleck, Elizabeth/0000-0003-0213-1250 FU NIH [AI118426, AI036629, U19 AI109725] FX This study was supported by grants from the NIH (AI118426, AI036629, U19 AI109725). NR 55 TC 12 Z9 12 U1 3 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD SEP-OCT PY 2015 VL 6 IS 5 AR e01157-15 DI 10.1128/mBio.01157-15 PG 14 WC Microbiology SC Microbiology GA CV8HK UT WOS:000364523100020 PM 26350966 ER PT J AU Hubbard, CS Hong, J Jiang, Z Ebrat, B Suyenobu, B Smith, S Heendeniya, N Naliboff, BD Tillisch, K Mayer, EA Labus, JS AF Hubbard, C. S. Hong, J. Jiang, Z. Ebrat, B. Suyenobu, B. Smith, S. Heendeniya, N. Naliboff, B. D. Tillisch, K. Mayer, E. A. Labus, J. S. TI Increased attentional network functioning related to symptom severity measures in females with irritable bowel syndrome SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE attention network test; chronic pain; fMRI; irritable bowel syndrome ID COGNITIVE CONTROL; CINGULATE CORTEX; EXECUTIVE CONTROL; VISUAL-ATTENTION; BRAIN RESPONSES; PAIN PERCEPTION; SCALE; INHIBITION; DEFICITS; SYSTEM AB Background Increased attention to gastrointestinal (GI) symptoms and disease-specific contexts may play an important role in the enhanced perception of visceral stimuli frequently reported in patients with irritable bowel syndrome (IBS). In this study, we test the hypothesis that altered attentional mechanisms underlie central pain amplification in IBS. Methods To evaluate brain networks that support alerting, orienting, and executive attention, we employed the attention network test (ANT), a modified flanker task which measures the efficiency of functioning of core attentional networks, during functional magnetic resonance imaging in 15 IBS patients (mean age = 31 [11.96]) and 14 healthy controls (HCs; mean age = 31 [10.91]). Key Results Patients with IBS, compared to HCs, showed shorter reaction times during the alerting and orienting conditions which were associated with greater activation of anterior midcingulate and insular cortices, and decreased activity in the right inferior frontal junction and supplementary motor cortex. Patients also showed activation in the dorsal medial prefrontal cortex and concurrent thalamic deactivation during the executive control portion of the ANT relative to HCs, but no group difference in reaction times were found. The activity in brain regions showing group differences during the ANT were associated with measures of GI-specific anxiety, pain catastrophizing, and fear of uncertainty. In IBS, activity in the anterior midcingulate during alerting correlated with duration of GI-symptoms and overall symptom severity. Conclusions (sic) Inferences Together, these results suggest that IBS patients have specific abnormalities in attentional network functioning and these deficits may underlie symptom-related anxiety, hypervigilance, and visceral hypersensitivity. C1 [Hubbard, C. S.; Hong, J.; Jiang, Z.; Ebrat, B.; Suyenobu, B.; Smith, S.; Heendeniya, N.; Naliboff, B. D.; Tillisch, K.; Mayer, E. A.; Labus, J. S.] Univ Calif Los Angeles, Gail & Gerald Oppenheimer Family Ctr Neurobiol St, Los Angeles, CA USA. [Hubbard, C. S.; Hong, J.; Ebrat, B.; Suyenobu, B.; Smith, S.; Heendeniya, N.; Naliboff, B. D.; Tillisch, K.; Mayer, E. A.; Labus, J. S.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Hubbard, C. S.] Univ Maryland, Sch Dent, Dept Neural & Pain Sci, Baltimore, MD 21201 USA. [Hubbard, C. S.] Boston Childrens Hosp, Ctr Pain & Brain, Boston, MA 02115 USA. [Hong, J.] Univ Calif Los Angeles, Biomed Engn, Los Angeles, CA USA. [Hong, J.; Naliboff, B. D.; Tillisch, K.; Mayer, E. A.; Labus, J. S.] PAIN, Los Angeles, CA USA. [Naliboff, B. D.; Mayer, E. A.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Mayer, E. A.] Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90024 USA. [Naliboff, B. D.; Mayer, E. A.; Labus, J. S.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Hubbard, CS (reprint author), Boston Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Ctr Pain & Brain, 300 Longwood Ave, Boston, MA 02115 USA. EM catherine.hubbard@childrens.harvard.edu OI Hubbard, Catherine/0000-0002-9139-2198 FU National Institutes of Health [K08 DK071626, R03 DK 084169, R01 DK48351]; CORE-Neuroimaging & Psychophysiology [P50 DK064539]; CORE-Administrative [R24 AT002681]; CORE-Administrative Core Enrichment [P30 DK041301, R01 AT007137, K23 DK073451, T32 DK007180] FX This research was supported by grants from the National Institutes of Health including K08 DK071626 (JSL), R03 DK 084169, R01 DK48351 (EAM), P50 DK064539 CORE-Neuroimaging & Psychophysiology (EAM), CORE-Administrative (EAM), R24 AT002681 (EAM), P30 DK041301 CORE-Administrative Core & Enrichment, R01 AT007137 (KT), K23 DK073451 (KT), and T32 DK007180 (DJ). NR 81 TC 4 Z9 4 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1350-1925 EI 1365-2982 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD SEP PY 2015 VL 27 IS 9 BP 1282 EP 1294 DI 10.1111/nmo.12622 PG 13 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA CW1KF UT WOS:000364747900011 PM 26087779 ER PT J AU Juliano, AF Ginat, DT Moonis, G AF Juliano, Amy F. Ginat, Daniel T. Moonis, Gul TI Imaging Review of the Temporal Bone: Part II. Traumatic, Postoperative, and Noninflammatory Nonneoplastic Conditions SO RADIOLOGY LA English DT Review ID SEMICIRCULAR CANAL DEHISCENCE; ENLARGED VESTIBULAR AQUEDUCT; SENSORINEURAL HEARING-LOSS; HIGH-RESOLUTION CT; BLUNT CEREBROVASCULAR INJURY; COCHLEAR OTOSCLEROSIS; OSSICULAR RECONSTRUCTION; DIAGNOSTIC-ACCURACY; TYMPANOSTOMY TUBES; MULTIDETECTOR CT AB The first part of this review of the temporal bone discussed anatomy of the temporal bone as well as inflammatory and neoplastic processes in the temporal bone region (1). This second part will first discuss trauma to the temporal bone and posttraumatic complications. The indications for common surgical procedures performed in the temporal bone and their postoperative imaging appearance are then presented. Finally, a few noninflammatory nonneoplastic entities involving the temporal bone are reviewed. They are relatively uncommon diagnoses compared with infectious or inflammatory diseases. However, because patients present with symptoms that are either common (hearing loss) or distinctive (sensorineural hearing loss in a child), they are important for the radiologist to be aware of and recognize. (C) RSNA, 2015 C1 [Juliano, Amy F.] Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. [Ginat, Daniel T.] Univ Chicago Med, Dept Radiol, Chicago, IL USA. [Moonis, Gul] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. RP Juliano, AF (reprint author), Massachusetts Eye & Ear Infirm, Dept Radiol, 243 Charles St, Boston, MA 02114 USA. EM amy_juliano@meei.harvard.edu NR 82 TC 3 Z9 3 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 2015 VL 276 IS 3 BP 654 EP 671 DI 10.1148/radiol.2015140800 PG 18 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CV6EM UT WOS:000364363500005 PM 26302389 ER PT J AU Kamath, AF Ong, KL Lau, E Chan, V Vail, TP Rubash, HE Berry, DJ Bozic, KJ AF Kamath, Atul F. Ong, Kevin L. Lau, Edmund Chan, Vanessa Vail, Thomas P. Rubash, Harry E. Berry, Daniel J. Bozic, Kevin J. TI Quantifying the Burden of Revision Total Joint Arthroplasty for Periprosthetic Infection SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total hip arthroplasty (replacement); total knee arthroplasty; revision arthroplasty; infection; epidemiology ID TOTAL KNEE ARTHROPLASTY; TOTAL HIP-ARTHROPLASTY; STATES MEDICARE POPULATION; UNITED-STATES; RISK-FACTORS; ECONOMIC BURDEN; POSTOPERATIVE MORTALITY; 2-STAGE REIMPLANTATION; HOSPITAL READMISSION; REPLACEMENT AB Periprosthetic joint infection (PJI) represents substantial clinical and economic burdens. This study evaluated patient and procedure characteristics and resource utilization associated with revision arthroplasty for PJI. The Nationwide Inpatient Sample (Q4 2005-2010) was analyzed for 235,857 revision THA (RTHA) and 301,718 revision TKA (RTKA) procedures. PJI was the most common indication for RTKA, and the third most common reason for RTHA. PJI was most commonly associated with major severity of illness (SOI) in RTHA, and with moderate SOI in RTKA. RTHA and RTKA for PJI had the longest length of stay. Costs were higher for RTHA/RTKA for PJI than for any other diagnosis except periprosthetic fracture. Epidemiologic differences exist in the rank, severity and populations for RTHA and RTKA for PJI. (C) 2015 Elsevier Inc. All rights reserved. C1 [Kamath, Atul F.] Penn Hosp, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. [Ong, Kevin L.] Exponent Inc, Philadelphia, PA USA. [Lau, Edmund] Exponent Inc, Menlo Pk, CA USA. [Chan, Vanessa; Vail, Thomas P.; Bozic, Kevin J.] Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94143 USA. [Chan, Vanessa; Bozic, Kevin J.] Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94143 USA. [Rubash, Harry E.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Berry, Daniel J.] Mayo Clin, Dept Orthopaed Surg, Rochester, MN USA. RP Bozic, KJ (reprint author), Univ Calif San Francisco, Dept Orthopaed Surg, 500 Parnassus Ave,MU 320W, San Francisco, CA 94143 USA. NR 52 TC 9 Z9 9 U1 0 U2 6 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 EI 1532-8406 J9 J ARTHROPLASTY JI J. Arthroplast. PD SEP PY 2015 VL 30 IS 9 BP 1492 EP 1497 DI 10.1016/j.arth.2015.03.035 PG 6 WC Orthopedics SC Orthopedics GA CV0OA UT WOS:000363948900003 PM 25865815 ER PT J AU Foster, SA Hambright, DS Antoci, V Greene, ME Malchau, H Kwon, YM AF Foster, Scott A. Hambright, Dustin S. Antoci, Valentin Greene, Meridith E. Malchau, Henrik Kwon, Young-Min TI Effects of Obesity on Health Related Quality of Life Following Total Hip Arthroplasty SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total hip arthroplasty; obesity; EQ-5D; health related quality of life; cost-effectiveness ID BODY-MASS INDEX; KNEE ARTHROPLASTY; PHYSICAL-ACTIVITY; MORBID-OBESITY; REPLACEMENT; RISK; OSTEOARTHRITIS; COMPLICATIONS; EQ-5D; CARE AB Obesity is known to negatively impact health related quality of life (HRQoL). Although non-disease specific tools have been used to study HRQoL after THA in obese patients, these do not directly measure health utility improvements. All 435 THA patients in the current study, regardless of BMI, reported improvement in HRQoL as measured by EQ-5D, a universal, standardized, non-disease specific preference-based instrument. These data suggest obese patients value their quality of life improvement following THA as much as non-obese patients. Furthermore, the increased activity level observed following THA in obese patients suggests obese patients may also obtain non-disease specific benefits of a more active lifestyle. This information is important for future assessments of value and cost-effectiveness of THA in the obese population. (C) 2015 Elsevier Inc. All rights reserved. C1 [Foster, Scott A.; Hambright, Dustin S.; Antoci, Valentin; Greene, Meridith E.; Malchau, Henrik; Kwon, Young-Min] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02114 USA. RP Kwon, YM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped Surg, 55 Fruit St,Yawkey 3B, Boston, MA 02114 USA. NR 33 TC 4 Z9 4 U1 0 U2 4 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 EI 1532-8406 J9 J ARTHROPLASTY JI J. Arthroplast. PD SEP PY 2015 VL 30 IS 9 BP 1551 EP 1554 DI 10.1016/j.arth.2015.03.023 PG 4 WC Orthopedics SC Orthopedics GA CV0OA UT WOS:000363948900015 PM 25887700 ER PT J AU Tiberi, JV Antoci, V Malchau, H Rubash, HE Freiberg, AA Kwon, YM AF Tiberi, John V., III Antoci, Valentin Malchau, Henrik Rubash, Harry E. Freiberg, Andrew A. Kwon, Young-Min TI What is the Fate of Total Hip Arthroplasty (THA) Acetabular Component Orientation When Evaluated in the Standing Position? SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total hip arthroplasty; acetabular cup position; standing; safe zone; EOS X-ray imaging Acquisition System ID CUP NAVIGATION; PELVIC TILT; IN-VITRO; REPLACEMENT; DISLOCATIONS; KINEMATICS; ANGLE; VIVO; WEAR AB This retrospective study measured the change of the acetabular component orientation between supine and standing radiographs in 113 THA patients and identified the associated anatomical parameters that may help direct pre-operative planning. The mean change of the acetabular component inclination and version from supine to standing was 4.6 degrees and 5.9 degrees respectively (P < 0.0001), with 49 (43%) hips showing inclination change >5 degrees and 69 (53%) hips showing version change >5 degrees. Twelve (43%) of 28 'malpositioned' cups became 'well-positioned' and 26 (31%) of 85 'well-positioned' cups became 'malpositioned' upon standing. Changes in inclination were associated with leg length discrepancy and pelvic obliquity; and changes in version were associated with pelvic tilt and pelvic incidence. Standing position and patient factors should be considered when defining "optimal" acetabular orientation. (C) 2015 Elsevier Inc. All rights reserved. C1 [Tiberi, John V., III; Antoci, Valentin; Malchau, Henrik; Rubash, Harry E.; Freiberg, Andrew A.; Kwon, Young-Min] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02114 USA. RP Kwon, YM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped Surg, 55 Fruit St,Yawkey 3B, Boston, MA 02114 USA. NR 27 TC 5 Z9 5 U1 3 U2 5 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 EI 1532-8406 J9 J ARTHROPLASTY JI J. Arthroplast. PD SEP PY 2015 VL 30 IS 9 BP 1555 EP 1560 DI 10.1016/j.arth.2015.03.025 PG 6 WC Orthopedics SC Orthopedics GA CV0OA UT WOS:000363948900016 PM 25863890 ER PT J AU Colman, MW Karim, SM Hirsch, JA Yoo, AJ Schwab, JH Hornicek, FJ Raskin, KA AF Colman, Matthew W. Karim, Syed M. Hirsch, Joshua A. Yoo, Albert J. Schwab, Joseph H. Hornicek, Francis J. Raskin, Kevin A. TI Percutaneous Acetabuloplasty Compared With Open Reconstruction for Extensive Periacetabular Carcinoma Metastases SO JOURNAL OF ARTHROPLASTY LA English DT Article DE periacetabular; metastasis; carcinoma; acetabuloplasty; cement; Harrington reconstruction ID ACETABULAR RECONSTRUCTION; BREAST-CANCER; CEMENT; VERTEBROPLASTY; INSUFFICIENCY; INJECTION; DISEASE; LESIONS; HIP AB For destructive metastatic periacetabular disease, options include open acetabular reconstruction or percutaneous cement acetabuloplasty (PA). We reviewed 28 consecutive patients with Harrington grade II or III lesions, 17 who underwent Harrington-type or anti-protrusio reconstruction and 11 who underwent PA. Primary outcome measures were performance status (PS), ambulatory status (0 = unassisted ambulation, 1 = assisted ambulation, 2 = nonambulatory), and 10-point VAS score. The surgery group had better pain reduction than the PA group at 3 months (3.6 vs. 1.5 points, P = 0.04), and a trend at final follow-up (3.8 vs. 1.4 points, P = 0.06). Improvement in ambulatory status was better in the surgery group at 3 months only (0.53 vs. -0.14, P = 0.03). Thus compared with PA, open reconstruction may provide improved pain relief and ambulation. (C) 2015 Elsevier Inc. All rights reserved. C1 [Colman, Matthew W.] Rush Univ, Midwest Orthoped, Chicago, IL 60612 USA. [Karim, Syed M.; Schwab, Joseph H.; Hornicek, Francis J.; Raskin, Kevin A.] Massachusetts Gen Hosp, Harvard Combined Dept Orthoped, Boston, MA 02114 USA. [Hirsch, Joshua A.; Yoo, Albert J.] Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. RP Colman, MW (reprint author), Rush Univ, Midwest Orthoped, 1611 West Harrison St,Suite 300, Chicago, IL 60612 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 EI 1532-8406 J9 J ARTHROPLASTY JI J. Arthroplast. PD SEP PY 2015 VL 30 IS 9 BP 1586 EP 1591 DI 10.1016/j.arth.2015.02.022 PG 6 WC Orthopedics SC Orthopedics GA CV0OA UT WOS:000363948900022 PM 26115981 ER PT J AU Kawasaki, M Tanaka, R Ono, K Minatoguchi, S Watanabe, T Iwama, M Hirose, T Arai, M Noda, T Watanabe, S Zile, MR Minatoguchi, S AF Kawasaki, Masanori Tanaka, Ryuhei Ono, Koji Minatoguchi, Shingo Watanabe, Takatomo Iwama, Makoto Hirose, Takeshi Arai, Masazumi Noda, Toshiyuki Watanabe, Sachiro Zile, Michael R. Minatoguchi, Shinya TI A novel ultrasound predictor of pulmonary capillary wedge pressure assessed by the combination of left atrial volume and function: A speckle tracking echocardiography study SO JOURNAL OF CARDIOLOGY LA English DT Article DE Atrial volume; Atrial function; Diastolic dysfunction; Speckle tracking echocardiography; Pulmonary capillary wedge pressure ID VENTRICULAR FILLING PRESSURES; PRESERVED EJECTION FRACTION; DOPPLER-ECHOCARDIOGRAPHY; DIASTOLIC DYSFUNCTION; HEART-FAILURE; MITRAL REGURGITATION; MECHANICAL FUNCTION; FIBRILLATION; CATHETERIZATION; DISTENSIBILITY AB Background: We hypothesized that a development of a novel index based on the combination of left atrial volume (LAV) and left atrial (LA) function evaluated by the time-LA volume curve using speckle tracking echocardiography (STE) would be accurate and useful to estimate pulmonary capillary wedge pressure (PCWP). Our goal was to develop a novel index of PCWP based on a combination of LAV and LA function using STE. Methods: A cross-validation study was performed with the patients divided into a training study to define the novel index (n = 50) and a testing study to validate the index (n = 196). PCWP was measured by right heart catheterization, and phasic LAV and emptying function (EF) were measured by STE. Results: Simple linear regression analysis in the training study revealed that the novel index that best estimated PCWP was the kinetics-tracking index [KT index = log(10) (active LAEF/minimum LAV index)]. Multiple regression analysis revealed that the KT index was the most reliable predictor of PCWP. It had the strongest correlation with PCWP (r = -0.86, p < 0.001) among all echocardiographic parameters. In the testing study, PCWP estimated by the KT index was also strongly correlated with measured PCWP (r = 0.92, p < 0.001). These correlations were also strong in the patients with reduced left ventricular ejection fraction (<50%), chronic heart failure, and chronic atrial fibrillation (r = 0.92, r = 0.91, r = 0.79, p < 0.001, respectively). Conclusions: A novel index (KT index) using a combination of LAV and LA function was a powerful and useful predictor of PCWP and may be valuable in routine clinical practice. (C) 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved. C1 [Kawasaki, Masanori; Minatoguchi, Shingo; Watanabe, Takatomo; Minatoguchi, Shinya] Gifu Univ, Grad Sch Med, Dept Cardiol, Gifu 5011194, Japan. [Tanaka, Ryuhei; Ono, Koji; Iwama, Makoto; Hirose, Takeshi; Arai, Masazumi; Noda, Toshiyuki; Watanabe, Sachiro] Gifu Prefectural Gen Med Ctr, Dept Cardiol, Gifu, Japan. [Zile, Michael R.] Med Univ S Carolina, Med Cardiol, Charleston, SC 29425 USA. [Zile, Michael R.] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. RP Kawasaki, M (reprint author), Gifu Univ, Grad Sch Med, Dept Cardiol, 1-1 Yanagido, Gifu 5011194, Japan. EM masanori@ya2.so-net.ne.jp NR 31 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0914-5087 EI 1876-4738 J9 J CARDIOL JI J. Cardiol. PD SEP-OCT PY 2015 VL 66 IS 3-4 BP 253 EP 262 DI 10.1016/j.jjcc.2014.11.008 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CV1BS UT WOS:000363988800013 PM 25547741 ER PT J AU Fry, JL Shiraishi, Y Turcotte, R Yu, XJ Gao, YZ Akiki, R Bachschmid, M Zhang, YH Morgan, KG Cohen, RA Seta, F AF Fry, Jessica L. Shiraishi, Yasunaga Turcotte, Raphael Yu, Xunjie Gao, Yuan Z. Akiki, Rachid Bachschmid, Markus Zhang, Yanhang Morgan, Kathleen G. Cohen, Richard A. Seta, Francesca TI Vascular Smooth Muscle Sirtuin-1 Protects Against Aortic Dissection During Angiotensin II-Induced Hypertension SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE angiotensin II; aortic dissection; sirtuin-1; vascular smooth muscle ID NEGATIVE REGULATOR; SIRT1 DEACETYLASE; CELL-SURVIVAL; MICE; MATRIX; DIET; WALL; MATRIX-METALLOPROTEINASE-9; INFLAMMATION; DYSFUNCTION AB Background-Sirtuin-1 (SirT1), a nicotinamide adenine dinucleotide(+)-dependent deacetylase, is a key enzyme in the cellular response to metabolic, inflammatory, and oxidative stresses; however, the role of endogenous SirT1 in the vasculature has not been fully elucidated. Our goal was to evaluate the role of vascular smooth muscle SirT1 in the physiological response of the aortic wall to angiotensin II, a potent hypertrophic, oxidant, and inflammatory stimulus. Methods and Results-Mice lacking SirT1 in vascular smooth muscle (ie, smooth muscle SirT1 knockout) had drastically high mortality (70%) caused by aortic dissection after angiotensin II infusion (1 mg/kg per day) but not after an equipotent dose of norepinephrine, despite comparable blood pressure increases. Smooth muscle SirT1 knockout mice did not show any abnormal aortic morphology or blood pressure compared with wild-type littermates. Nonetheless, in response to angiotensin II, aortas from smooth muscle SirT1 knockout mice had severely disorganized elastic lamellae with frequent elastin breaks, increased oxidant production, and aortic stiffness compared with angiotensin II-treated wild-type mice. Matrix metalloproteinase expression and activity were increased in the aortas of angiotensin II-treated smooth muscle SirT1 knockout mice and were prevented in mice overexpressing SirT1 in vascular smooth muscle or with use of the oxidant scavenger tempol. Conclusions-Endogenous SirT1 in aortic smooth muscle is required to maintain the structural integrity of the aortic wall in response to oxidant and inflammatory stimuli, at least in part, by suppressing oxidant-induced matrix metalloproteinase activity. SirT1 activators could potentially be a novel therapeutic approach to prevent aortic dissection and rupture in patients at risk, such as those with hypertension or genetic disorders, such as Marfan's syndrome. C1 [Fry, Jessica L.; Shiraishi, Yasunaga; Akiki, Rachid; Bachschmid, Markus; Cohen, Richard A.; Seta, Francesca] Boston Univ, Vasc Biol Sect, Boston, MA 02118 USA. [Turcotte, Raphael; Gao, Yuan Z.; Zhang, Yanhang] Boston Univ, Dept Biomed Engn, Boston, MA 02118 USA. [Yu, Xunjie; Zhang, Yanhang] Boston Univ, Dept Mech Engn, Boston, MA 02118 USA. [Gao, Yuan Z.; Morgan, Kathleen G.] Boston Univ, Dept Hlth Sci, Boston, MA 02118 USA. [Turcotte, Raphael] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Adv Microscopy Program,Ctr Syst Biol, Boston, MA USA. [Turcotte, Raphael] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Seta, F (reprint author), Boston Univ, Sch Med, Vasc Biol Sect, 650 Albany St,X726, Boston, MA 02118 USA. EM setaf@bu.edu OI Fry, Jessica/0000-0003-2748-0334; Bachschmid, Markus Michael/0000-0002-0748-5528 FU NHLBI [HL105287, HL098028]; Servier Research Institute (Suresnes, France); Evans Center for Interdisciplinary Biomedical Research ARC at Boston University; Ruth Kirschstein Postdoctoral Fellowship at the Whitaker Cardiovascular Institute Multidisciplinary Training Program [T32 HL07224]; Marfan's Foundation Early Investigator grant FX This work was supported by NHLBI R01 grant HL105287 to Cohen and was partially supported by a grant from Servier Research Institute (Suresnes, France), the Evans Center for Interdisciplinary Biomedical Research ARC at Boston University (http://www.bumc.bu.edu/evanscenteribr/), NHLBI R01 grant HL098028 to Zhang, Ruth Kirschstein Postdoctoral Fellowship T32 HL07224 at the Whitaker Cardiovascular Institute Multidisciplinary Training Program to Fry and The Marfan's Foundation Early Investigator grant to Seta. NR 37 TC 8 Z9 8 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD SEP PY 2015 VL 4 IS 9 AR e002384 DI 10.1161/JAHA.115.002384 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CV3IH UT WOS:000364152100027 PM 26376991 ER PT J AU Rodriguez, F Foody, JM Wang, Y Lopez, L AF Rodriguez, Fatima Foody, JoAnne M. Wang, Yun Lopez, Lenny TI Young Hispanic Women Experience Higher In-Hospital Mortality Following an Acute Myocardial Infarction SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE acute myocardial infarction; disparities; outcomes; race/ethnicity; sex-based differences ID CORONARY-REVASCULARIZATION PROCEDURES; CARDIOVASCULAR DATA REGISTRY; RAPID RISK STRATIFICATION; SUPPRESS ADVERSE OUTCOMES; ISCHEMIC-HEART-DISEASE; QUALITY-OF-CARE; SEX-DIFFERENCES; RACIAL-DIFFERENCES; CARDIAC REVASCULARIZATION; EARLY IMPLEMENTATION AB Background-Although mortality rates for acute myocardial infarction (AMI) have declined for men and women, prior studies have reported a sex gap in mortality such that younger women were most likely to die after an AMI. Methods and Results-We sought to explore the impact of race and ethnicity on the sex gap in AMI patterns of care and mortality for younger women in a contemporary patient cohort. We constructed multivariable hierarchical logistic regression models to examine trends in AMI hospitalizations, procedures, and in-hospital mortality by sex, age (<65 and >= 65 years), and race/ethnicity (white, black, and Hispanic). Analyses were derived from 194 071 patients who were hospitalized for an AMI with available race and ethnicity data from the 2009-2010 National Inpatient Sample. Hospitalization rates, procedures (coronary angiography, percutaneous coronary interventions, and cardiac bypass surgery), and inpatient mortality were analyzed across age, sex, and race/ethnic groups. There was significant variation in hospitalization rates by age and race/ethnicity. All racial/ethnic groups were less likely to undergo invasive procedures compared with white men (P<0.001). After adjustment for comorbidities, younger Hispanic women experienced higher in-hospital mortality compared with younger white men, with an odds ratio of 1.5 (95% CI 1.2 to 1.9), adjusted for age and comorbidities. Conclusion-We found significant racial and sex disparities in AMI hospitalizations, care patterns, and mortality, with higher in-hospital mortality experienced by younger Hispanic women. Future studies are necessary to explore determinants of these significant racial and sex disparities in outcomes for AMI. C1 [Rodriguez, Fatima] Stanford Univ, Div Cardiovasc Med, Stanford, CA 94305 USA. [Foody, JoAnne M.; Lopez, Lenny] Harvard Univ, Sch Med, Boston, MA USA. [Lopez, Lenny] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Lopez, Lenny] Massachusetts Gen Hosp, Dispar Solut Ctr, Boston, MA 02114 USA. [Lopez, Lenny] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Foody, JoAnne M.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Wang, Yun] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Lopez, L (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM llopez1@partners.org FU Linda Joy Pollin Cardiovascular Wellness Center at Brigham; Women's Hospital; Robert Wood Johnson Foundation Harold Amos Faculty Development Program; NIDDK [1K23DK098280-01] FX Dr Foody has received funding for this work through the Linda Joy Pollin Cardiovascular Wellness Center at Brigham and Women's Hospital. Drs Rodriguez, Lopez, and Wang have no conflicts to declare. Dr Lopez thanks the Robert Wood Johnson Foundation Harold Amos Faculty Development Program and NIDDK 1K23DK098280-01. NR 39 TC 2 Z9 2 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD SEP PY 2015 VL 4 IS 9 AR e002089 DI 10.1161/JAHA.115.002089 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CV3IH UT WOS:000364152100010 PM 26353998 ER PT J AU McCarty, WJ Prodanov, L Bale, SS Bhushan, A Jindal, R Yarmush, ML Usta, OB AF McCarty, William J. Prodanov, Ljupcho Bale, Shyam Sundhar Bhushan, Abhinav Jindal, Rohit Yarmush, Martin L. Usta, O. Berk TI Layer-by-layer Collagen Deposition in Microfluidic Devices for Microtissue Stabilization SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Bioengineering; Issue 103; Collagen; layer-by-layer deposition; microfluidics; hepatocyte; methylation; succinylation; liver microtissue ID POLYELECTROLYTE MULTILAYERS; IN-VITRO; HEPATOCYTES; PROTEINS; CULTURE; CELLS AB Although microfluidics provides exquisite control of the cellular microenvironment, culturing cells within microfluidic devices can be challenging. 3D culture of cells in collagen type I gels helps to stabilize cell morphology and function, which is necessary for creating microfluidic tissue models in microdevices. Translating traditional 3D culture techniques for tissue culture plates to microfluidic devices is often difficult because of the limited channel dimensions. In this method, we describe a technique for modifying native type I collagen to generate polycationic and polyanionic collagen solutions that can be used with layer-by-layer deposition to create ultrathin collagen assemblies on top of cells cultured in microfluidic devices. These thin collagen layers stabilize cell morphology and function, as shown using primary hepatocytes as an example cell, allowing for the long term culture of microtissues in microfluidic devices. C1 [McCarty, William J.; Prodanov, Ljupcho; Bale, Shyam Sundhar; Bhushan, Abhinav; Jindal, Rohit; Yarmush, Martin L.; Usta, O. Berk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Cambridge, MA 02138 USA. [McCarty, William J.; Prodanov, Ljupcho; Bale, Shyam Sundhar; Bhushan, Abhinav; Jindal, Rohit; Yarmush, Martin L.; Usta, O. Berk] Shriners Hosp Children Boston, Boston, MA USA. RP Yarmush, ML (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Cambridge, MA 02138 USA. EM ireis@sbi.org; berkusta@gmail.com OI McCarty, William/0000-0002-3671-0616 FU National Institutes of Health; National Center for Advancing Translational Sciences [UH2TR000503]; Ruth L. Kirschstein National Research Service Award [F32DK098905]; National Institute of Diabetes and Digestive and Kidney Diseases [DK095984] FX This work was supported by grants from the National Institutes of Health, including a microphysiological systems consortium grant from the National Center for Advancing Translational Sciences (UH2TR000503), a Ruth L. Kirschstein National Research Service Award Postdoctoral Fellowship (F32DK098905 for WJM) and pathway to independence award (DK095984 for AB) from the National Institute of Diabetes and Digestive and Kidney Diseases. NR 19 TC 0 Z9 0 U1 3 U2 9 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD SEP PY 2015 IS 103 AR e53078 DI 10.3791/53078 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CV4FL UT WOS:000364222300030 ER PT J AU Kopans, DB AF Kopans, Daniel B. TI The UK Age Trial: screening women in their forties SO LANCET ONCOLOGY LA English DT Editorial Material ID BREAST-CANCER; MORTALITY REDUCTION C1 [Kopans, Daniel B.] Harvard Univ, Sch Med, Boston, MA 02163 USA. [Kopans, Daniel B.] Massachusetts Gen Hosp, Wang Ambulatory Care Ctr, Boston, MA 02114 USA. RP Kopans, DB (reprint author), Harvard Univ, Sch Med, Boston, MA 02163 USA. EM dkopans@partners.org NR 11 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD SEP PY 2015 VL 16 IS 9 BP 1012 EP 1013 DI 10.1016/S1470-2045(15)00057-1 PG 3 WC Oncology SC Oncology GA CV0TL UT WOS:000363966100038 PM 26206145 ER PT J AU Pastore, A Jurinovic, V Kridel, R Hoster, E Staiger, AM Szczepanowski, M Pott, C Kopp, N Murakami, M Horn, H Leich, E Moccia, AA Mottok, A Sunkavalli, A Van Hummelen, P Ducar, M Ennishi, D Shulha, HP Hother, C Connors, JM Sehn, LH Dreyling, M Neuberg, D Moller, P Feller, AC Hansmann, ML Stein, H Rosenwald, A Ott, G Klapper, W Unterhalt, M Hiddemann, W Gascoyne, RD Weinstock, DM Weigert, O AF Pastore, Alessandro Jurinovic, Vindi Kridel, Robert Hoster, Eva Staiger, Annette M. Szczepanowski, Monika Pott, Christiane Kopp, Nadja Murakami, Mark Horn, Heike Leich, Ellen Moccia, Alden A. Mottok, Anja Sunkavalli, Ashwini Van Hummelen, Paul Ducar, Matthew Ennishi, Daisuke Shulha, Hennady P. Hother, Christoffer Connors, Joseph M. Sehn, Laurie H. Dreyling, Martin Neuberg, Donna Moeller, Peter Feller, Alfred C. Hansmann, Martin L. Stein, Harald Rosenwald, Andreas Ott, German Klapper, Wolfram Unterhalt, Michael Hiddemann, Wolfgang Gascoyne, Randy D. Weinstock, David M. Weigert, Oliver TI Integration of gene mutations in risk prognostication for patients receiving first-line immunochemotherapy for follicular lymphoma: a retrospective analysis of a prospective clinical trial and validation in a population-based registry SO LANCET ONCOLOGY LA English DT Article ID B-CELL LYMPHOMA; LOW-GRADE LYMPHOMA; EZH2 MUTATIONS; RITUXIMAB; INDEX; CYCLOPHOSPHAMIDE; TRANSFORMATION; VINCRISTINE; COMBINATION; DOXORUBICIN AB Background Follicular lymphoma is a clinically and genetically heterogeneous disease, but the prognostic value of somatic mutations has not been systematically assessed. We aimed to improve risk stratification of patients receiving first-line immunochemotherapy by integrating gene mutations into a prognostic model. Methods We did DNA deep sequencing to retrospectively analyse the mutation status of 74 genes in 151 follicular lymphoma biopsy specimens that were obtained from patients within 1 year before beginning immunochemotherapy consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). These patients were recruited between May 4, 2000, and Oct 20, 2010, as part of a phase 3 trial (GLSG2000). Eligible patients had symptomatic, advanced stage follicular lymphoma and were previously untreated. The primary endpoints were failure-free survival (defined as less than a partial remission at the end of induction, relapse, progression, or death) and overall survival calculated from date of treatment initiation. Median follow-up was 7.7 years (IQR 5.5-9.3). Mutations and clinical factors were incorporated into a risk model for failure-free survival using multivariable L1-penalised Cox regression. We validated the risk model in an independent population-based cohort of 107 patients with symptomatic follicular lymphoma considered ineligible for curative irradiation. Pretreatment biopsies were taken between Feb 24, 2004, and Nov 24, 2009, within 1 year before beginning first-line immunochemotherapy consisting of rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP). Median follow-up was 6.7 years (IQR 5.7-7.6). Findings We established a clinicogenetic risk model (termed m7-FLIPI) that included the mutation status of seven genes (EZH2, ARID1A, MEF2B, EP300, FOXO1, CREBBP, and CARD11), the Follicular Lymphoma International Prognostic Index (FLIPI), and Eastern Cooperative Oncology Group (ECOG) performance status. In the training cohort, m7-FLIPI defined a high-risk group (28%, 43/151) with 5-year failure-free survival of 38.29% (95% CI 25.31-57.95) versus 77.21% (95% CI 69.21-86.14) for the low-risk group (hazard ratio [HR] 4.14, 95% CI 2.47-6.93; p<0.0001; bootstrap-corrected HR 2.02), and outperformed a prognostic model of only gene mutations (HR 3.76, 95% CI 2.10-6.74; p<0.0001; bootstrap-corrected HR 1.57). The positive predictive value and negative predictive value for 5-year failure-free survival were 64% and 78%, respectively, with a C-index of 0.80 (95% CI 0.71-0.89). In the validation cohort, m7-FLIPI again defined a high-risk group (22%, 24/107) with 5-year failure-free survival of 25.00% (95% CI 12.50-49.99) versus 68.24% (58.84-79.15) in the low-risk group (HR 3.58, 95% CI 2.00-6.42; p<0.0001). The positive predictive value for 5-year failure-free survival was 72% and 68% for negative predictive value, with a C-index of 0.79 (95% CI 0.69-0.89). In the validation cohort, risk stratification by m7-FLIPI outperformed FLIPI alone (HR 2.18, 95% CI 1.21-3.92), and FLIPI combined with ECOG performance status (HR 2.03, 95% CI 1.12-3.67). Interpretation Integration of the mutational status of seven genes with clinical risk factors improves prognostication for patients with follicular lymphoma receiving first-line immunochemotherapy and is a promising approach to identify the subset at highest risk of treatment failure. C1 [Pastore, Alessandro; Jurinovic, Vindi; Hoster, Eva; Dreyling, Martin; Weigert, Oliver] Univ Munich, Univ Hosp, Dept Internal Med 3, D-81377 Munich, Germany. [Jurinovic, Vindi; Hoster, Eva] Univ Munich, Inst Med Informat Biometry & Epidemiol, D-81377 Munich, Germany. [Kridel, Robert; Moccia, Alden A.; Mottok, Anja; Ennishi, Daisuke; Shulha, Hennady P.; Hother, Christoffer; Connors, Joseph M.; Sehn, Laurie H.; Gascoyne, Randy D.] British Columbia Canc Agcy, Dept Lymphoid Canc Res, Vancouver, BC V5Z 4E6, Canada. [Kridel, Robert; Moccia, Alden A.; Ennishi, Daisuke; Shulha, Hennady P.; Hother, Christoffer; Connors, Joseph M.; Sehn, Laurie H.; Gascoyne, Randy D.] British Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 4E6, Canada. [Staiger, Annette M.; Horn, Heike; Ott, German] Robert Bosch Krankenhaus, Dept Clin, Stuttgart, Germany. [Staiger, Annette M.; Horn, Heike] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany. [Staiger, Annette M.; Horn, Heike] Univ Tubingen, Tubingen, Germany. [Szczepanowski, Monika; Klapper, Wolfram] Univ Hosp Schleswig Holstein, Haematopathol Sect, Kiel, Germany. [Pott, Christiane] Univ Hosp Schleswig Holstein, Dept Med 2, Kiel, Germany. [Sunkavalli, Ashwini; Van Hummelen, Paul; Ducar, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Leich, Ellen; Rosenwald, Andreas] Univ Wurzburg, Inst Pathol, D-97070 Wurzburg, Germany. [Leich, Ellen; Rosenwald, Andreas] Comprehens Canc Ctr Mainfranken, Wurzburg, Germany. [Moeller, Peter] Univ Ulm, Inst Pathol, D-89069 Ulm, Germany. [Feller, Alfred C.] Univ Hosp Schleswig Holstein, Dept Pathol, Lubeck, Germany. [Hansmann, Martin L.] Goethe Univ Frankfurt, Senckenberg Inst Pathol, D-60054 Frankfurt, Germany. [Stein, Harald] Reference Ctr Lymphoma & Haematopathol, Berlin, Germany. [Hiddemann, Wolfgang; Weigert, Oliver] Helmholtz Ctr Munich, Clin Cooperat Grp Leukemia, Munich, Germany. [Hiddemann, Wolfgang; Weigert, Oliver] German Canc Consortium DKTK, Heidelberg, Germany. [Hiddemann, Wolfgang; Weigert, Oliver] German Canc Res Ctr, Heidelberg, Germany. RP Weigert, O (reprint author), Univ Munich, Univ Hosp, Dept Internal Med 3, Marchioninistr 15, D-81377 Munich, Germany. EM oliver.weigert@med.uni-muenchen.de RI Klapper, Wolfram/S-6314-2016 FU Max-Eder Program of the Deutsche Krebshilfe e.V. [110659]; Terry Fox Research Institute [1023]; Ligue Genevoise Contre le Cancer et Fondation Dr Henri Dubois-Ferriere Dinu Lipatti; Canadian Institutes for Health Research; Michael Smith Foundation for Health Research; University of British Columbia; Mildred Scheel Cancer Foundation of the Deutsche Krebshilfe e.V.; Alfred Benzon Foundation; Genome British Columbia; Genome Canada; British Columbia Cancer Foundation; Roche Pharma AG FX This research was supported by the Max-Eder Program of the Deutsche Krebshilfe e.V. (number 110659 to OW) and in part by a Program Project Grant from the Terry Fox Research Institute to JMC and RDG (number 1023). AP is a Mildred-Scheel Postdoctoral Research Fellow of the Deutsche Krebshilfe e.V. (number 111354). RK is supported by fellowships from the Ligue Genevoise Contre le Cancer et Fondation Dr Henri Dubois-Ferriere Dinu Lipatti, the Canadian Institutes for Health Research, the Michael Smith Foundation for Health Research, and the University of British Columbia. AM holds a fellowship awarded by the Mildred Scheel Cancer Foundation of the Deutsche Krebshilfe e.V. CH is funded by a postdoctoral fellowship from The Alfred Benzon Foundation. JMC is partially supported by Genome British Columbia, Genome Canada, the Canadian Institutes for Health Research, and the British Columbia Cancer Foundation. DMW is a Leukemia and Lymphoma Society Scholar. The GLSG2000 trial was partially supported by Roche Pharma AG. NR 35 TC 43 Z9 43 U1 4 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD SEP PY 2015 VL 16 IS 9 BP 1111 EP 1122 DI 10.1016/S1470-2045(15)00169-2 PG 12 WC Oncology SC Oncology GA CV0TL UT WOS:000363966100053 PM 26256760 ER PT J AU Lucas, MS Brawner, BM Hardie, TL Beacham, B Paidipati, C Diaz, M Lauer, A Hobbie, WL Deatrick, JA AF Lucas, Matthew S. Brawner, Bridgette M. Hardie, Thomas L. Beacham, Barbara Paidipati, Cynthia Diaz, Magdaline Lauer, Amy Hobbie, Wendy L. Deatrick, Janet A. TI Assessing Suicidal Ideation and Behaviors Among Survivors of Childhood Brain Tumors and Their Mothers During Sociobehavioral Research SO ONCOLOGY NURSING FORUM LA English DT Article DE suicidal ideation; suicide; brain neoplasms; survivors ID POSTTRAUMATIC STRESS SYMPTOMS; ANTIDEPRESSANT EFFICACY TRIALS; QUALITY-OF-LIFE; ADULT SURVIVORS; CANCER-PATIENTS; UNITED-STATES; RISK; ADOLESCENT; DISORDER; EVENTS AB Purpose/Objectives: To describe the development and feasibility of a protocol for nonpsychiatric subspecialty research staff members to screen research participants who endorse suicidal ideations or behaviors during data collection. Design: Descriptive protocol development. Setting: The Children's Hospital of Philadelphia and the University of Pennsylvania. Sample: 186 mother caregivers and 134 adolescent or young adult survivors of childhood brain tumors, with the protocol implemented for 5 caregivers and 11 survivors. Methods: During telephone-and home-based interviews, the interviewer assessed the participant using the Columbia-Suicide Severity Rating Scale (C-SSRS). Main Research Variables: Expressed suicidal ideation or behavior. Findings: Implementation of the C-SSRS by nonpsychiatric subspecialty staff members was feasible and valid. Interviewers' conclusions based on this instrument matched those of the mental health professional who followed up with participants. Process notes contained themes about the participants, including anger and sadness in survivors and the physical and emotional demands of the survivor in caregivers. Progress notes for the interviewer included a reiteration of events, whether the assessment was successful, and whether the recommendation of the interviewer was in agreement with that of the mental health professional. Conclusions: The protocol based on the C-SSRS was useful and feasible for nonpsychiatric subspecialty staff members to use in the collection of data from survivors of childhood brain tumors and their caregivers. Implications for Nursing: Survivors of childhood brain tumors and their caregivers may experience psychosocial distress. Nurses, as research assistants or in other roles, can use tools such as the C-SSRS to assist in front-line assessments. C1 [Lucas, Matthew S.] Temple Univ, Sch Med, Ctr Bioeth Urban Hlth & Policy, Philadelphia, PA 19122 USA. [Lucas, Matthew S.] Temple Univ, Dept Philosophy, Philadelphia, PA 19122 USA. [Brawner, Bridgette M.; Deatrick, Janet A.] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA. [Brawner, Bridgette M.] Univ Penn, Sch Nursing, Ctr Global Womens Hlth, Philadelphia, PA 19104 USA. [Hardie, Thomas L.; Paidipati, Cynthia; Diaz, Magdaline] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Beacham, Barbara] Indiana Univ, Sch Nursing, Indianapolis, IN 46204 USA. [Paidipati, Cynthia; Lauer, Amy] Childrens Hosp Philadelphia, Philadelphia, PA USA. [Hobbie, Wendy L.] Childrens Hosp Philadelphia, Canc Survivorship Program, Philadelphia, PA USA. [Deatrick, Janet A.] Univ Penn, Sch Nursing, Hlth Community Practices, Philadelphia, PA 19104 USA. RP Lucas, MS (reprint author), Temple Univ, Sch Med, Ctr Bioeth Urban Hlth & Policy, Philadelphia, PA 19122 USA. EM matthew.lucas@temple.edu OI Hardie, Thomas/0000-0002-4547-7991 FU U.S. National Institutes of Health via the National Institute of Nursing Research [T32NR007100, F31NR013091, R01NR009651]; American Cancer Society [122552-DSCN-10-089]; ONS Foundation FX Matthew S. Lucas, PhD, MBE, RN, is a graduate programs coordinator in the Center for Bioethics, Urban Health, and Policy in the School of Medicine and an adjunct assistant professor in the Department of Philosophy, both at Temple University in Philadelphia, PA; Bridgette M. Brawner, PhD, APRN, is an assistant professor of nursing in the Center for Health Equity Research and Center for Global Women's Health in the School of Nursing and Thomas L. Hardie, EdD, PMHCNS-BC, is an adjunct professor, both in the School of Nursing at the University of Pennsylvania in Philadelphia; Barbara Beacham, PhD, RN, is a postdoctoral fellow/assistant research scientist in the School of Nursing at Indiana University in Indianapolis; Cynthia Paidipati, MSN, CRNP, is a doctoral student in the School of Nursing at the University of Pennsylvania and a psychiatric nurse practitioner at Children's Hospital of Philadelphia; Magdaline Diaz, RN, is a student in the School of Nursing at the University of Pennsylvania; Amy Lauer, MSN, CRNP, is a pediatric oncology nurse and Wendy L. Hobbie, MSN, CRNP, FAAN, is an associate director in the Cancer Survivorship Program, both at the Children's Hospital of Philadelphia; and Janet A. Deatrick, PhD, RN, FAAN, is a professor and director in the Center for Health Equity Research and the Shearer Endowed Term Chair in Healthy Community Practices in the School of Nursing at the University of Pennsylvania. This research was funded by grants from the U.S. National Institutes of Health via the National Institute of Nursing Research (T32NR007100, F31NR013091 [MSL]; R01NR009651 [JAD]), the American Cancer Society (122552-DSCN-10-089 [MSL]), and the ONS Foundation (Neuro-Oncology Nursing Grant [JAD]). Lucas can be reached at matthew.lucas@temple.edu, with copy to editor at ONFEditor@ons.org. (Submitted February 2015. Accepted for publication April 13, 2015.) NR 46 TC 0 Z9 0 U1 4 U2 10 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 SEP PY 2015 VL 42 IS 5 BP E319 EP E329 DI 10.1188/15.ONF.42-05AP PG 11 WC Oncology; Nursing SC Oncology; Nursing GA CU9VA UT WOS:000363892900001 PM 26302289 ER PT J AU Falconi, M Crippa, S Chari, S Conlon, K Kim, SW Levy, P Tanaka, M Werner, J Wolfgang, CL Pezzilli, R Castillo, CFD AF Falconi, Massimo Crippa, Stefano Chari, Suresh Conlon, Kevin Kim, Sun-Whe Levy, Philippe Tanaka, Masao Werner, Jens Wolfgang, Christopher L. Pezzilli, Raffaele Castillo, Carlos Fernandez-del TI Quality assessment of the guidelines on cystic neoplasms of the pancreas SO PANCREATOLOGY LA English DT Review DE ADAPTE method; AGREE instrument; Diagnosis; Follow-up; Pancreatic cystic lesions; Mucinous cystic neoplasm ID PAPILLARY MUCINOUS NEOPLASMS; INTERNATIONAL-CONSENSUS-GUIDELINES; MANAGEMENT; DIAGNOSIS; OPERATE; LESIONS AB Background: Though cystic pancreatic neoplasms (CPNs) are being increasingly detected, their evaluation and management are still debated and have lead to publication of multiple guidelines for diagnostic work-up, indications for resection, and non-operative management with follow-up strategies of CPNs. Aims: To analyze available guidelines in order to evaluate their overall quality and clinical applicability, indications for surgical resection and its extent, modalities and timing of follow-up when non-operative management is indicated. Methods: After a systematic search of the English literature, we selected eight guidelines for assessment according to the Appraisal of Guidelines, Research and Evaluation in Europe (AGREE) II instrument. Results: One guideline received the lower AGREE score regarding the "scope and purpose", "rigor of development" and "clarity and presentation" domains, whereas one received the best score for "stake-holder involvement" domain. No differences were found among different guidelines regarding the "applicability". The overall quality assessment score showed that only two guidelines were significantly lower than the others. According to the practical utilization recommendation score, four guidelines were considered as having full applicability in clinical practice. Conclusion: Existing guidelines provide adequate guidance, at least with the present knowledge, for the management of cystic pancreatic lesions; however, not any one was satisfactory to all aspects related to the management of CPN. An update of the existing guidelines should be considered if and when more evidence-based data are available. Copyright (C) 2015, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved. C1 [Falconi, Massimo; Crippa, Stefano] Univ Politecn Marche, Osped Riuniti, Div Pancreat Surg, Ancona, Italy. [Chari, Suresh] Mayo Clin, Div Gastroenterol & Hepatol, Pancreas Interest Grp, Rochester, MN USA. [Conlon, Kevin] Univ Ireland Trinity Coll, Dept Surg, Dublin, Ireland. [Kim, Sun-Whe] Seoul Natl Univ, Coll Med, Dept Surg, Seoul, South Korea. [Levy, Philippe] Hosp Beaujon, AP HP, Serv Gastroenterol Pancreatol, Fac Denis Diderot,DHU Unity,Pole Malad Appareil D, Paris, France. [Tanaka, Masao] Kyushu Univ, Grad Sch Med Sci, Dept Surg & Oncol, Fukuoka 8128582, Japan. [Werner, Jens] Univ Munich, Dept Surg, Munich, Germany. [Wolfgang, Christopher L.] Johns Hopkins Univ, Dept Surg, Baltimore, MD USA. [Wolfgang, Christopher L.] Johns Hopkins Univ, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD USA. [Pezzilli, Raffaele] St Orsola Malpighi Hosp, Dept Digest Syst, Pancreas Unit, I-40138 Bologna, Italy. [Castillo, Carlos Fernandez-del] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pancreas & Biliary Program,Dept Surg, Boston, MA 02115 USA. RP Pezzilli, R (reprint author), St Orsola Malpighi Hosp, Dept Digest Syst, Pancreas Unit, Via Massarenti 9, I-40138 Bologna, Italy. EM raffaele.pezzilli@aosp.bo.it RI U-ID, Kyushu/C-5291-2016; OI Pezzilli, Raffaele/0000-0001-9827-7451; Falconi, Massimo/0000-0001-9654-7243 NR 22 TC 4 Z9 4 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-3903 EI 1424-3911 J9 PANCREATOLOGY JI Pancreatology PD SEP-OCT PY 2015 VL 15 IS 5 BP 463 EP 469 DI 10.1016/j.pan.2015.05.478 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CV1DA UT WOS:000363992300003 PM 26100659 ER PT J AU Reddy, LF Horan, WP Barch, DM Buchanan, RW Dunayevich, E Gold, JM Lyons, N Marder, SR Treadway, MT Wynn, JK Young, JW Green, MF AF Reddy, L. Felice Horan, William P. Barch, Deanna M. Buchanan, Robert W. Dunayevich, Eduardo Gold, James M. Lyons, Naomi Marder, Stephen R. Treadway, Michael T. Wynn, Jonathan K. Young, Jared W. Green, Michael F. TI Effort-Based Decision-Making Paradigms for Clinical Trials in Schizophrenia: Part 1-Psychometric Characteristics of 5 Paradigms SO SCHIZOPHRENIA BULLETIN LA English DT Article DE schizophrenia; effort; motivation; psychometric ID NEGATIVE SYMPTOMS; PHYSICAL EFFORT; VALIDATION; ANHEDONIA; TASK AB Impairments in willingness to exert effort contribute to the motivational deficits characteristic of the negative symptoms of schizophrenia. The current study evaluated the psychometric properties of 5 new or adapted paradigms to determine their suitability for use in clinical trials of schizophrenia. This study included 94 clinically stable participants with schizophrenia and 40 healthy controls. The effort-based decision-making battery was administered twice to the schizophrenia group (baseline, 4-week retest) and once to the control group. The 5 paradigms included 1 that assesses cognitive effort, 1 perceptual effort, and 3 that assess physical effort. Each paradigm was evaluated on (1) patient vs healthy control group differences, (2) test-retest reliability, (3) utility as a repeated measure (ie, practice effects), and (4) tolerability. The 5 paradigms showed varying psychometric strengths and weaknesses. The Effort Expenditure for Rewards Task showed the best reliability and utility as a repeated measure, while the Grip Effort Task had significant patient-control group differences, and superior tolerability and administration duration. The other paradigms showed weaker psychometric characteristics in their current forms. These findings highlight challenges in adapting effort and motivation paradigms for use in clinical trials. C1 [Reddy, L. Felice; Horan, William P.; Lyons, Naomi; Marder, Stephen R.; Wynn, Jonathan K.; Green, Michael F.] VISN 22 Mental Illness Res Educ & Clin Ctr, Dept Vet Affairs, Los Angeles, CA USA. [Reddy, L. Felice; Horan, William P.; Marder, Stephen R.; Wynn, Jonathan K.; Green, Michael F.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Barch, Deanna M.] Washington Univ, Dept Psychol, Dept Psychiat, St Louis, MO 63130 USA. [Barch, Deanna M.] Washington Univ, Dept Radiol, St Louis, MO 63130 USA. [Buchanan, Robert W.; Gold, James M.] Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. [Dunayevich, Eduardo] Amgen Inc, Thousand Oaks, CA 91320 USA. [Treadway, Michael T.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Young, Jared W.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Young, Jared W.] VA San Diego Healthcare Syst, Res Serv, San Diego, CA USA. RP Reddy, LF (reprint author), VA Greater Los Angeles Healthcare Syst, MIRECC 210A,Bldg 210,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM lenafelice@ucla.edu RI Wynn, Jonathan/H-3749-2014 OI Wynn, Jonathan/0000-0002-1763-8540 FU Amgen, Inc. FX This project was an investigator-initiated research collaboration funded by Amgen, Inc. NR 32 TC 12 Z9 12 U1 7 U2 11 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 SEP PY 2015 VL 41 IS 5 BP 1045 EP 1054 DI 10.1093/schbul/sbv089 PG 10 WC Psychiatry SC Psychiatry GA CV0YM UT WOS:000363979800009 PM 26142081 ER PT J AU Horan, WP Reddy, LF Barch, DM Buchanan, RW Dunayevich, E Gold, JM Marder, SR Wynn, JK Young, JW Green, MF AF Horan, William P. Reddy, L. Felice Barch, Deanna M. Buchanan, Robert W. Dunayevich, Eduardo Gold, James M. Marder, Steven R. Wynn, Jonathan K. Young, Jared W. Green, Michael F. TI Effort-Based Decision-Making Paradigms for Clinical Trials in Schizophrenia: Part 2-External Validity and Correlates SO SCHIZOPHRENIA BULLETIN LA English DT Article DE schizophrenia; effort; decision making; functional outcome ID NEGATIVE SYMPTOMS; INCENTIVE MOTIVATION; EFFORT ALLOCATION; REWARD; IMPAIRMENT; ACTIVATION; NEUROCOGNITION; VALIDATION; ANHEDONIA; MEDIATOR AB Effort-based decision making has strong conceptual links to the motivational disturbances that define a key subdomain of negative symptoms. However, the extent to which effort-based decision-making performance relates to negative symptoms, and other clinical and functionally important variables has yet to be systematically investigated. In 94 clinically stable outpatients with schizophrenia, we examined the external validity of 5 effort-based paradigms, including the Effort Expenditure for Rewards, Balloon Effort, Grip Strength Effort, Deck Choice Effort, and Perceptual Effort tasks. These tasks covered 3 types of effort: physical, cognitive, and perceptual. Correlations between effort related performance and 6 classes of variables were examined, including: (1) negative symptoms, (2) clinically rated motivation and community role functioning, (3) self-reported motivational traits, (4) neurocognition, (5) other psychiatric symptoms and clinical/demographic characteristics, and (6) subjective valuation of monetary rewards. Effort paradigms showed small to medium relationships to clinical ratings of negative symptoms, motivation, and functioning, with the pattern more consistent for some measures than others. They also showed small to medium relations with neurocognitive functioning, but were generally unrelated to other psychiatric symptoms, self-reported traits, antipsychotic medications, side effects, and subjective valuation of money. There were relatively strong interrelationships among the effort measures. In conjunction with findings from a companion psychometric article, all the paradigms warrant further consideration and development, and 2 show the strongest potential for clinical trial use at this juncture. C1 [Horan, William P.; Reddy, L. Felice; Marder, Steven R.; Wynn, Jonathan K.; Green, Michael F.] VISN 22 Mental Illness Res Educ & Clin Ctr, Dept Vet Affairs, Los Angeles, CA USA. [Horan, William P.; Reddy, L. Felice; Marder, Steven R.; Wynn, Jonathan K.; Green, Michael F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Horan, William P.; Reddy, L. Felice; Marder, Steven R.; Wynn, Jonathan K.; Green, Michael F.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Barch, Deanna M.] Washington Univ, Dept Psychol, Dept Psychiat, St Louis, MO 63130 USA. [Barch, Deanna M.] Washington Univ, Dept Radiol, St Louis, MO 63130 USA. [Buchanan, Robert W.; Gold, James M.] Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. [Dunayevich, Eduardo] Amgen Inc, Thousand Oaks, CA 91320 USA. [Young, Jared W.] Univ Calif San Diego, Dept Psychiat, San Deigo, CA USA. [Young, Jared W.] VA San Diego Healthcare Syst, Res Serv, San Diego, CA USA. RP Horan, WP (reprint author), VA Greater Los Angeles Healthcare Syst, MIRECC 210A,Bldg 210,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM horan@ucla.edu RI Wynn, Jonathan/H-3749-2014 OI Wynn, Jonathan/0000-0002-1763-8540 FU Amgen, Inc. FX This project was an investigator-initiated research collaboration funded by Amgen, Inc. NR 40 TC 10 Z9 10 U1 9 U2 13 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 SEP PY 2015 VL 41 IS 5 BP 1055 EP 1065 DI 10.1093/schbul/sbv090 PG 11 WC Psychiatry SC Psychiatry GA CV0YM UT WOS:000363979800010 PM 26209546 ER PT J AU Gupta, CN Calhoun, VD Rachakonda, S Chen, JY Patel, V Liu, JY Segall, J Franke, B Zwiers, MP Arias-Vasquez, A Buitelaar, J Fisher, SE Fernandez, G van Erp, TGM Potkin, S Ford, J Mathalon, D McEwen, S Lee, HJ Mueller, BA Greve, DN Andreassen, O Agartz, I Gollub, RL Sponheim, SR Ehrlich, S Wang, L Pearlson, G Glahn, DC Sprooten, E Mayer, AR Stephen, J Jung, RE Canive, J Bustillo, J Turner, JA AF Gupta, Cota Navin Calhoun, Vince D. Rachakonda, Srinivas Chen, Jiayu Patel, Veena Liu, Jingyu Segall, Judith Franke, Barbara Zwiers, Marcel P. Arias-Vasquez, Alejandro Buitelaar, Jan Fisher, Simon E. Fernandez, Guillen van Erp, Theo G. M. Potkin, Steven Ford, Judith Mathalon, Daniel McEwen, Sarah Lee, Hyo Jong Mueller, Bryon A. Greve, Douglas N. Andreassen, Ole Agartz, Ingrid Gollub, Randy L. Sponheim, Scott R. Ehrlich, Stefan Wang, Lei Pearlson, Godfrey Glahn, David C. Sprooten, Emma Mayer, Andrew R. Stephen, Julia Jung, Rex E. Canive, Jose Bustillo, Juan Turner, Jessica A. TI Patterns of Gray Matter Abnormalities in Schizophrenia Based on an International Mega-analysis SO SCHIZOPHRENIA BULLETIN LA English DT Article DE independent component analysis; schizophrenia; source-based morphometry; symptoms; voxel-based morphometry ID VOXEL-BASED MORPHOMETRY; MULTISITE STRUCTURAL MRI; ALZHEIMERS-DISEASE; BRAIN VOLUMES; METAANALYSIS; DISORDER; ANATOMY; ILLNESS; SCORES AB Analyses of gray matter concentration (GMC) deficits in patients with schizophrenia (Sz) have identified robust changes throughout the cortex. We assessed the relationships between diagnosis, overall symptom severity, and patterns of gray matter in the largest aggregated structural imaging dataset to date. We performed both source-based morphometry (SBM) and voxel-based morphometry (VBM) analyses on GMC images from 784 Sz and 936 controls (Ct) across 23 scanning sites in Europe and the United States. After correcting for age, gender, site, and diagnosis by site interactions, SBM analyses showed 9 patterns of diagnostic differences. They comprised separate cortical, subcortical, and cerebellar regions. Seven patterns showed greater GMC in Ct than Sz, while 2 (brainstem and cerebellum) showed greater GMC for Sz. The greatest GMC deficit was in a single pattern comprising regions in the superior temporal gyrus, inferior frontal gyrus, and medial frontal cortex, which replicated over analyses of data subsets. VBM analyses identified overall cortical GMC loss and one small cluster of increased GMC in Sz, which overlapped with the SBM brainstem component. We found no significant association between the component loadings and symptom severity in either analysis. This mega-analysis confirms that the commonly found GMC loss in Sz in the anterior temporal lobe, insula, and medial frontal lobe form a single, consistent spatial pattern even in such a diverse dataset. The separation of GMC loss into robust, repeatable spatial patterns across multiple datasets paves the way for the application of these methods to identify subtle genetic and clinical cohort effects. C1 [Gupta, Cota Navin; Calhoun, Vince D.; Rachakonda, Srinivas; Chen, Jiayu; Patel, Veena; Liu, Jingyu; Segall, Judith; Stephen, Julia; Turner, Jessica A.] Mind Res Network, Albuquerque, NM USA. [Calhoun, Vince D.; Canive, Jose; Bustillo, Juan] Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA. [Calhoun, Vince D.; Liu, Jingyu] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. [Calhoun, Vince D.; Canive, Jose; Bustillo, Juan] Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. [Calhoun, Vince D.; Glahn, David C.; Sprooten, Emma] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Franke, Barbara; Arias-Vasquez, Alejandro] Radboud Univ Nijmegen, Med Ctr, Dept Psychiat & Human Genet, NL-6525 ED Nijmegen, Netherlands. [Franke, Barbara; Zwiers, Marcel P.; Buitelaar, Jan; Fisher, Simon E.; Fernandez, Guillen] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, NL-6525 ED Nijmegen, Netherlands. [Fisher, Simon E.] Max Planck Inst Psycholinguist, Dept Language & Genet, Nijmegen, Netherlands. [van Erp, Theo G. M.; Potkin, Steven] Univ Calif Irvine, Sch Med, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. [Ford, Judith; Mathalon, Daniel] Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94143 USA. [McEwen, Sarah] Univ Calif San Francisco, Dept Psychiat & Biobehav Sci, San Francisco, CA 94143 USA. [Lee, Hyo Jong] Chonbuk Natl Univ, Div Elect & Informat Engn, Jeonju, South Korea. [Mueller, Bryon A.; Sponheim, Scott R.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Greve, Douglas N.; Gollub, Randy L.; Ehrlich, Stefan] MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA. [Andreassen, Ole; Agartz, Ingrid] Univ Oslo, Inst Clin Med, KG Jebsen Ctr Psychosis Res, NORMENT, Oslo, Norway. [Andreassen, Ole] Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway. [Agartz, Ingrid] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. [Agartz, Ingrid] Diakonhjemmet Hosp, Dept Res, Oslo, Norway. [Gollub, Randy L.] HMS, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. [Sponheim, Scott R.] Minneapolis VA Healthcare Syst, Minneapolis, MN USA. [Ehrlich, Stefan] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Child & Adolescent Psychiat, Dresden, Germany. [Wang, Lei] Northwestern Univ, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. [Wang, Lei] Northwestern Univ, Dept Radiol, Chicago, IL 60611 USA. [Pearlson, Godfrey; Glahn, David C.; Sprooten, Emma] Hartford Healthcare Corp, Inst Living, Hartford, CT USA. [Pearlson, Godfrey] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT USA. [Jung, Rex E.] Univ New Mexico, Hlth Sci Ctr, Dept Neurosurg, Albuquerque, NM 87131 USA. [Canive, Jose] Raymond G Murphy VA Med Ctr, Albuquerque, NM USA. [Turner, Jessica A.] Georgia State Univ, Dept Psychol, Atlanta, GA 30302 USA. [Turner, Jessica A.] Georgia State Univ, Inst Neurosci, Atlanta, GA 30302 USA. RP Turner, JA (reprint author), Georgia State Univ, Dept Psychol, POB 5010, Atlanta, GA 30302 USA. EM jturner@mrn.org RI Fernandez, Guillen/B-3771-2009; Franke, Barbara/D-4836-2009; Zwiers, Marcel/D-2968-2009; Fisher, Simon/E-9130-2012; Arias Vasquez, Alejandro/E-4762-2012; OI Fernandez, Guillen/0000-0002-5522-0604; Franke, Barbara/0000-0003-4375-6572; Zwiers, Marcel/0000-0001-5483-2935; Fisher, Simon/0000-0002-3132-1996; Arias Vasquez, Alejandro/0000-0002-4786-0169; Stephen, Julia/0000-0003-2486-747X; Liu, Jingyu/0000-0002-1724-7523 FU National Institute of Mental Health [1R01MH094524-01A1] FX Primary funding for this project was provided by National Institute of Mental Health (1R01MH094524-01A1 to V.D.C. and J.A.T.). NR 43 TC 17 Z9 19 U1 2 U2 5 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 SEP PY 2015 VL 41 IS 5 BP 1133 EP 1142 DI 10.1093/schbul/sbu177 PG 10 WC Psychiatry SC Psychiatry GA CV0YM UT WOS:000363979800018 PM 25548384 ER PT J AU Alvarez, NN Zhu, A Arellano, RS Randolph, MA Duggan, M Arn, JS Huang, CA Sachs, DH Vagefi, PA AF Alvarez, Nalu Navarro Zhu, Alexander Arellano, Ronald S. Randolph, Mark A. Duggan, Michael Arn, John Scott Huang, Christene A. Sachs, David H. Vagefi, Parsia A. TI Postnatal xenogeneic B-cell tolerance in swine following in utero intraportal antigen exposure SO XENOTRANSPLANTATION LA English DT Article DE B-cell tolerance; in utero tolerance; xenotransplant ID BONE-MARROW-TRANSPLANTATION; CIRCULATING ANTIBODY; ALLOGRAFT TOLERANCE; CHIMERISM; REPERTOIRE; INJECTION; ROUTE; FETAL; PIGS; ADJUVANTS AB Background: The objective of this study was to investigate the humoral immune response to xenogeneic antigens administered during the fetal state utilizing a baboon-to-pig model. Methods: Nine fetuses from an alpha-1,3-galactosyltransferase gene knockout (GalT-KO) 1MGH-miniature swine sow underwent transuterine ultrasound-guided intraportal injection of T-cell depleted baboon bone marrow (B-BM) at mid-gestation. Two juvenile GalT-KO swine undergoing direct B-BM intraportal injection were used as controls. Results: Postnatal humoral tolerance was induced in the long-term surviving piglets as demonstrated by the absence of any antibody response to baboon donor cells. In addition, a second intraportal B-BM administration at 2.5 months post-birth led to no antibody formation despite re-exposure to xenogeneic antigens. This B-cell unresponsiveness was abrogated only when the animal was exposed subcutaneously to third-party xenogeneic and allogeneic antigens, suggesting that the previously achieved humoral non-responsiveness was donor specific. In comparison, the two juvenile GalT-KO control swine demonstrated increasing anti-baboon IgM and IgG levels following intraportal injection. Conclusions: In summary, xenogeneic B-cell tolerance was induced through in utero intraportal exposure to donor cells and this tolerance persisted following postnatal rechallenge with donor B-BM, but was lost on exposure to third-party antigen, possibly as a result of cross-reactive antibody formation. C1 [Alvarez, Nalu Navarro; Zhu, Alexander; Arellano, Ronald S.; Randolph, Mark A.; Duggan, Michael; Arn, John Scott; Huang, Christene A.; Sachs, David H.; Vagefi, Parsia A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Vagefi, PA (reprint author), Massachusetts Gen Hosp, 55 Fruit St,White 521c, Boston, MA 02114 USA. EM pvagefi@mgh.harvard.edu FU American College of Surgeons Faculty Research Fellowship; Massachusetts General Hospital Faculty Development Fellowship FX PAV is a recipient of an American College of Surgeons Faculty Research Fellowship and a Massachusetts General Hospital Faculty Development Fellowship. NR 32 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0908-665X EI 1399-3089 J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2015 VL 22 IS 5 BP 368 EP 378 DI 10.1111/xen.12186 PG 11 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA CU9LR UT WOS:000363866500005 ER PT J AU Purdon, PL Zhou, DW Akeju, O Brown, EN AF Purdon, Patrick L. Zhou, David W. Akeju, Oluwaseun Brown, Emery N. TI Propofol-induced Electroencephalogram Dynamics: A Missing Piece Reply SO ANESTHESIOLOGY LA English DT Letter ID INDUCED ALPHA-RHYTHM; GENERAL-ANESTHESIA; INDUCED UNCONSCIOUSNESS; COHERENCE ANALYSIS; CONSCIOUSNESS; STATES; SLEEP C1 [Purdon, Patrick L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Purdon, PL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM patrickp@nmr.mgh.harvard.edu FU NIGMS NIH HHS [TR01-GM104948, T32 GM007592, R01 GM104948, T32GM007592]; NIH HHS [DP2 OD006454, DP1 OD003646, DP2-OD006454, DP1-OD003646] NR 31 TC 0 Z9 0 U1 0 U2 2 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 SEP PY 2015 VL 123 IS 3 BP 725 EP 728 DI 10.1097/ALN.0000000000000794 PG 4 WC Anesthesiology SC Anesthesiology GA CU4YG UT WOS:000363536900034 PM 26284863 ER PT J AU Cantor, AB AF Cantor, Alan B. TI Myeloid proliferations associated with Down syndrome SO JOURNAL OF HEMATOPATHOLOGY LA English DT Review DE Down syndrome; Myeloid proliferation; Myeloproliferative disorder; GATA1 ID TRANSIENT MYELOPROLIFERATIVE DISORDER; ACUTE MEGAKARYOBLASTIC LEUKEMIA; ACUTE MEGAKARYOCYTIC LEUKEMIA; TRANSCRIPTION FACTOR GATA-1; HIGH CURE RATE; NATURAL-HISTORY; MOUSE MODEL; MUTATIONS; TRISOMY-21; CHILDREN AB A subset of Down syndrome (DS) (trisomy 21) neonates is born with a unique erythromegakaryocytic myeloproliferative disorder that spontaneously resolves over the first few months of life (DS-transient abnormal myelopoiesis (DS-TAM); previously called DS-transient myeloproliferative disorder (DS-TMD) and DS-transient leukemia (DS-TL)). These infants are at high risk for developing subsequent acute megakaryoblastic leukemia (myeloid leukemia associated with Down syndrome (ML-DS); previously called DS-acute megakaryoblastic leukemia (DS-AMKL)). The molecular basis for DS-TAM/ML-DS remained mysterious for a long period of time. However, new genetic insights have been gained over the past 12 years that have begun to decipher the pathophysiology of this unusual disorder. C1 [Cantor, Alan B.] Harvard Univ, Div Pediat Hematol Oncol, Boston Childrens Hosp, Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA. [Cantor, Alan B.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Cantor, AB (reprint author), Harvard Univ, Div Pediat Hematol Oncol, Boston Childrens Hosp, Dana Farber Canc Inst,Med Sch, 300 Longwood Ave Karp 7,Mailstop BCH3142, Boston, MA 02115 USA. EM alan.cantor@childrens.harvard.edu FU National Institutes of Health [P01 HL32262] FX This work was supported by the National Institutes of Health grant P01 HL32262. NR 62 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1868-9256 EI 1865-5785 J9 J HEMATOP JI J. Hematop. PD SEP PY 2015 VL 8 IS 3 BP 169 EP 176 DI 10.1007/s12308-014-0225-0 PG 8 WC Hematology; Pathology SC Hematology; Pathology GA CU8AJ UT WOS:000363762800007 PM 26753010 ER PT J AU Cheng, ER Palta, M Poehlmann-Tynan, J Witt, WP AF Cheng, Erika R. Palta, Mari Poehlmann-Tynan, Julie Witt, Whitney P. TI The Influence of Children's Cognitive Delay and Behavior Problems on Maternal Depression SO JOURNAL OF PEDIATRICS LA English DT Article ID PRESCHOOL-AGED CHILDREN; INTELLECTUAL DISABILITY; DEVELOPMENTAL-DISABILITIES; YOUNG-CHILDREN; EARLY-CHILDHOOD; MENTAL-HEALTH; PRIMARY-CARE; PARENTING STRESS; CAREGIVER STRESS; FAMILIES AB Objective To determine the impact of children's cognitive delay and behavior on maternal depressive symptoms using a large national cohort of US families. Study design Data were drawn from 2 waves of the nationally representative Early Childhood Longitudinal Study, Birth Cohort (n = 7550). Cognitive delay was defined at age 24 months by the lowest 10th percentile of the Bayley Short Form-Research Edition. At age 4 years, the children's behavior was assessed using the Preschool and Kindergarten Behavior Scales, administered to mothers and primary nonparental child care providers, and maternal depressive symptoms with the Center for Epidemiological Studies Depression Scale. Weighted generalized estimating equation models examined whether the children's behavior mediated the relationship between their cognitive delay status at 24 months and 4-year maternal depressive outcomes. Results At age 4 years, 26.9% of mothers of children with cognitive delay reported high depressive symptoms, compared with 17.4% of mothers of typically developing children (P < .0001). When the children's behavior was accounted for, the effect of cognitive delay on maternal depressive symptoms decreased by 36% (P < .0001). These findings remained significant when the children's behaviors were assessed by their primary nonparental care providers. Conclusion Caring for a child with a cognitive delay influences maternal depressive symptoms in part through the child's behavior problems. Preventive interventions to ameliorate adverse outcomes for children with cognitive delay and their families should consider the impact of the children's behavior. C1 [Cheng, Erika R.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Cheng, Erika R.] MassGen Hosp Children, Div Gen Acad Pediat, Boston, MA 02114 USA. [Palta, Mari] Univ Wisconsin, Dept Populat Hlth Sci, Sch Med & Publ Hlth, Madison, WI USA. [Palta, Mari] Univ Wisconsin, Waisman Ctr, Dept Biostat & Med Informat, Madison, WI 53705 USA. [Poehlmann-Tynan, Julie] Univ Wisconsin, Waisman Ctr, Dept Human Dev & Family Studies, Madison, WI 53705 USA. [Witt, Whitney P.] Truven Hlth Analyt, Div Maternal & Child Hlth Res, Durham, NC USA. RP Cheng, ER (reprint author), MassGen Hosp Children, Div Gen Acad Pediat, 100 Cambridge St,1570-C5, Boston, MA 02114 USA. EM erikarcheng@gmail.com FU National Research Service Award [T32HD075727-02] FX Supported in part by a National Research Service Award (T32HD075727-02 [to E.C.; PI: J.A. Finkelstein]). The authors declare no conflicts of interest. NR 53 TC 2 Z9 2 U1 3 U2 13 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD SEP PY 2015 VL 167 IS 3 BP 679 EP 686 DI 10.1016/j.jpeds.2015.06.003 PG 8 WC Pediatrics SC Pediatrics GA CU4ZI UT WOS:000363540200037 PM 26163083 ER PT J AU He, S Craig, BA Xu, HP Covinsky, KE Stallard, E Thomas, J Hass, Z Sands, LP AF He, Shuang Craig, Bruce A. Xu, Huiping Covinsky, Kenneth E. Stallard, Eric Thomas, Joseph, III Hass, Zach Sands, Laura P. TI Unmet Need for ADL Assistance Is Associated With Mortality Among Older Adults With Mild Disability SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Activities of daily living; Mortality; Unmet need ID PERSONAL ASSISTANCE; FUNCTIONAL STATUS; ELDERLY-PEOPLE; CARE NEEDS; HOSPITALIZATION; CONSEQUENCES; RISK; HELP AB Background. Unmet need for assistance with activities of daily living (ADLs) disability is associated with increased risk for future hospitalization. To further explore the association between unmet ADL need and future health outcomes, we examined the association between unmet need for ADL assistance and 1-year mortality. Methods. A prospective study of 6,730 community-living Medicare recipients was conducted among respondents to the 1994, 1999, and/or 2004 National Long Term Care Survey. Only those who reported having one or more ADL disabilities were included. Time to death within 1 year after the community survey was determined from Centers for Medicare and Medicaid Services vital statistics records. The community interviews provided demographic, health, and ADL information. Results. Unadjusted 1-year death rates were 8.7%, 10.6%, 11.4%, 19.2%, and 27.3%, respectively, for respondents with disabilities in 1, 2, 3, 4, and 5 ADLs. Overall, 21.3% reported unmet need for assistance for one or more ADL disabilities. After controlling for demographic and health characteristics, we found a significant interaction between unmet ADL need and level of ADL disability (p =.018). Post hoc analyses revealed that unmet ADL need was associated with increased risk for mortality only for those with one (hazard ratio = 1.96; 95% CI = 1.29-2.87) or two ADL disabilities (hazard ratio = 1.37; 95% CI = 1.07-1.75), but not for those with three or more ADL disabilities. Conclusion. Future studies are needed to determine whether these findings are replicable and, if so, whether physiologic or process of care variables explain why ADL is associated with mortality only for those with mild disability. C1 [He, Shuang; Craig, Bruce A.; Hass, Zach] Purdue Univ, Dept Stat, W Lafayette, IN 47907 USA. [Xu, Huiping] Indiana Univ, Sch Med, Indianapolis, IN USA. [Covinsky, Kenneth E.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Div Geriatr, San Francisco, CA 94143 USA. [Stallard, Eric] Duke Univ, Ctr Populat Hlth & Aging, Durham, NC USA. [Thomas, Joseph, III] Purdue Univ, Coll Pharm, Ctr Aging & Life Course, Regenstrief Ctr Healthcare Engn,Ctr Hlth Outcomes, W Lafayette, IN 47907 USA. [Sands, Laura P.] Purdue Univ, Sch Nursing, W Lafayette, IN 47907 USA. [Sands, Laura P.] Purdue Univ, Ctr Aging & Life Course, W Lafayette, IN 47907 USA. RP Sands, LP (reprint author), Virginia Tech, Ctr Gerontol, 237 Wallace Hall 0426, Blacksburg, VA 24061 USA. EM lsands@vt.edu RI Craig, Bruce/D-5797-2017; Sands, Laura/E-8919-2015 OI Craig, Bruce/0000-0001-9346-467X; Sands, Laura/0000-0003-2446-4486 FU National Institute on Aging at the National Institutes of Health [R01AG034160] FX This research was funded by a grant from the National Institute on Aging at the National Institutes of Health (R01AG034160 to L.P.S.). NR 16 TC 1 Z9 1 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD SEP PY 2015 VL 70 IS 9 BP 1128 EP 1132 DI 10.1093/gerona/glv028 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CU4FK UT WOS:000363482300011 PM 25834196 ER PT J AU Katz, IT Siedner, MJ AF Katz, Ingrid T. Siedner, Mark J. TI Does early ART in sub-Saharan Africa decrease mortality? SO LANCET HIV LA English DT Editorial Material ID ANTIRETROVIRAL THERAPY; HIV CARE; INFECTION; ADULTS C1 [Katz, Ingrid T.] Brigham & Womens Hosp, Div Womens Hlth, Boston, MA 02115 USA. [Katz, Ingrid T.; Siedner, Mark J.] Harvard Univ, Sch Med, Boston, MA USA. [Katz, Ingrid T.; Siedner, Mark J.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. RP Katz, IT (reprint author), Brigham & Womens Hosp, Div Womens Hlth, 75 Francis St, Boston, MA 02115 USA. EM ikatz2@partners.org FU NIMH NIH HHS [K23 MH099916, K23 MH097667] NR 12 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 2352-3018 J9 LANCET HIV JI Lancet HIV PD SEP PY 2015 VL 2 IS 9 BP E354 EP E355 DI 10.1016/S2352-3018(15)00130-7 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CU8LI UT WOS:000363793700003 PM 26423540 ER PT J AU Gros, DF Szafranski, DD Brady, KT Back, SE AF Gros, Daniel F. Szafranski, Derek D. Brady, Kathleen T. Back, Sudie E. TI Relations Between Pain, PTSD Symptoms, and Substance Use in Veterans SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; ADDICTION SEVERITY INDEX; COMORBID CHRONIC PAIN; MUTUAL MAINTENANCE; PSYCHOMETRIC PROPERTIES; SOMATIC SYMPTOMS; PRIMARY-CARE; PREVALENCE; DEPRESSION; RISK AB Objective: The frequent co-occurrence of posttraumatic stress disorder (PTSD) and chronic pain has received much attention in the literature. However, the extant literature is limited in that these investigations generally exclude patients with co-occurring substance use disorders (SUD). Thus, the present study investigated symptoms of PTSD and SUD in veterans with high and low pain symptoms. Method: Veterans (N = 136) seeking treatment for comorbid symptoms of PTSD and SUD were recruited as part of a larger study. All participants completed a baseline assessment, which included a series of diagnostic interviews and self-report questionnaires measuring symptoms of pain, PTSD and SUD. Results: Higher levels of self-reported pain were found to be associated with both self-reported and clinician-rated PTSD symptoms above and beyond the influence of the demographic variables. However, no reliable relations were demonstrated between substance use and pain. Conclusions: Although preliminary, the findings highlight the common occurrence of chronic pain among veterans with comorbid PTSD/SUD, and the potential impact of pain on clinical presentation. The findings may help inform special considerations for assessment and treatment practices for this high-risk population. C1 [Gros, Daniel F.; Szafranski, Derek D.; Brady, Kathleen T.; Back, Sudie E.] Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Gros, Daniel F.; Szafranski, Derek D.; Brady, Kathleen T.; Back, Sudie E.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA. RP Gros, DF (reprint author), Mental Hlth Serv, 116,Ralph H Johnson VAMC,109 Bee St, Charleston, SC 29401 USA. EM grosd@musc.edu FU NIDA [DA021228]; Department of Veteran Affairs CSR&D Career Development Award [CX000845] FX This research was supported by NIDA grant DA021228 (PI: Back) and Department of Veteran Affairs CSR&D Career Development Award CX000845 (PI: Gros). NR 41 TC 1 Z9 1 U1 2 U2 5 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 FAL PY 2015 VL 78 IS 3 BP 277 EP 287 DI 10.1080/00332747.2015.1069659 PG 11 WC Psychiatry SC Psychiatry GA CU5UG UT WOS:000363596900012 PM 26391835 ER PT J AU Ramanadhan, S Galarce, E Xuan, ZM Alexander-Molloy, J Viswanath, K AF Ramanadhan, Shoba Galarce, Ezequiel Xuan, Ziming Alexander-Molloy, Jaclyn Viswanath, Kasisomayajula TI Addressing the Vaccine Hesitancy Continuum: An Audience Segmentation Analysis of American Adults Who Did Not Receive the 2009 H1N1 Vaccine SO VACCINES LA English DT Article DE Vaccine hesitancy; audience segmentation; communication; public engagement; H1N1 ID UNITED-STATES; ATTITUDES; PARENTS; COVERAGE; BELIEFS; REFUSAL AB Understanding the heterogeneity of groups along the vaccine hesitancy continuum presents an opportunity to tailor and increase the impact of public engagement efforts with these groups. Audience segmentation can support these goals, as demonstrated here in the context of the 2009 H1N1 vaccine. In March 2010, we surveyed 1569 respondents, drawn from a nationally representative sample of American adults, with oversampling of racial/ethnic minorities and persons living below the United States Federal Poverty Level. Guided by the Structural Influence Model, we assessed knowledge, attitudes, and behaviors related to H1N1; communication outcomes; and social determinants. Among those who did not receive the vaccine (n = 1166), cluster analysis identified three vaccine-hesitant subgroups. Disengaged Skeptics (67%) were furthest from vaccine acceptance, with low levels of concern and engagement. The Informed Unconvinced (19%) were sophisticated consumers of media and health information who may not have been reached with information to motivate vaccination. The Open to Persuasion cluster (14%) had the highest levels of concern and motivation and may have required engagement about vaccination broadly. There were significant sociodemographic differences between groups. This analysis highlights the potential to use segmentation techniques to identify subgroups on the vaccine hesitancy continuum and tailor public engagement efforts accordingly. C1 [Ramanadhan, Shoba; Alexander-Molloy, Jaclyn; Viswanath, Kasisomayajula] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02215 USA. [Ramanadhan, Shoba; Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Galarce, Ezequiel] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94704 USA. [Xuan, Ziming] Boston Univ, Sch Publ Hlth, Crosstown Ctr, Boston, MA 02118 USA. RP Ramanadhan, S (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 450 Brookline Ave,LW 601, Boston, MA 02215 USA. EM shoba_ramanadhan@dfci.harvard.edu; galarcee@berkeley.edu; zxuan@bu.edu; jaclyn_alexander-molloy@dfci.harvard.edu; vish_viswanath@dfci.harvard.edu FU OPHPR CDC HHS [P01 TP000307] NR 44 TC 0 Z9 0 U1 1 U2 2 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2076-393X J9 VACCINES JI Vaccines PD SEP PY 2015 VL 3 IS 3 BP 556 EP 578 DI 10.3390/vaccines3030556 PG 23 WC Immunology SC Immunology GA CU2SM UT WOS:000363373600005 PM 26350595 ER PT J AU Petrick, JL Freedman, ND Graubard, BI Sahasrabuddhe, VV Lai, GY Alavanja, MC Beane-Freeman, LE Boggs, DA Buring, JE Chan, AT Chong, DQ Fuchs, CS Gapstur, SM Gaziano, JM Giovannucci, EL Hollenbeck, AR King, LY Koshiol, J Lee, IM Linet, MS Palmer, JR Poynter, JN Purdue, MP Robien, K Schairer, C Sesso, HD Sigurdson, AJ Zeleniuch-Jacquotte, A Wactawski-Wende, J Campbell, PT McGlynn, KA AF Petrick, Jessica L. Freedman, Neal D. Graubard, Barry I. Sahasrabuddhe, Vikrant V. Lai, Gabriel Y. Alavanja, Michael C. Beane-Freeman, Laura E. Boggs, Deborah A. Buring, Julie E. Chan, Andrew T. Chong, Dawn Q. Fuchs, Charles S. Gapstur, Susan M. Gaziano, John Michael Giovannucci, Edward L. Hollenbeck, Albert R. King, Lindsay Y. Koshiol, Jill Lee, I-Min Linet, Martha S. Palmer, Julie R. Poynter, Jenny N. Purdue, Mark P. Robien, Kim Schairer, Catherine Sesso, Howard D. Sigurdson, Alice J. Zeleniuch-Jacquotte, Anne Wactawski-Wende, Jean Campbell, Peter T. McGlynn, Katherine A. TI Coffee Consumption and Risk of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma by Sex: The Liver Cancer Pooling Project SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BASE-LINE CHARACTERISTICS; UNITED-STATES; WOMENS HEALTH; LARGE COHORT; ASSOCIATION; EPIDEMIOLOGY; METAANALYSIS; DISEASE; DESIGN; JAPAN AB Background: Coffee consumption has been reported to be inversely associated with hepatocellular carcinoma (HCC), the most common type of liver cancer. Caffeine has chemopreventive properties, but whether caffeine is responsible for the coffee-HCC association is not well studied. In addition, few studies have examined the relationship by sex, and no studies have examined whether there is an association between coffee and intrahepatic cholangiocarcinoma (ICC), the second most common type of liver cancer. Methods: In the Liver Cancer Pooling Project, a consortium of U. S.-based cohort studies, data from 1,212,893 individuals (HCC, n = 860; ICC, n = 260) in nine cohorts were pooled. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated using proportional hazards regression. Results: Higher coffee consumption was associated with lower risk of HCC (HR>3 cups/day vs. non-drinker, 0.73; 95% CI, 0.53-0.99; P-trend cups/day = <0.0001). More notable reduced risk was seen among women than men (P-interaction = 0.07). Women who consumed more than three cups of coffee per day were at a 54% lower risk of HCC (HR, 0.46; 95% CI, 0.26-0.81), whereas men had more modest reduced risk of HCC (HR, 0.93; 95% CI, 0.63-1.37). The associations were stronger for caffeinated coffee (HR>3 cups/day vs. non-drinker, 0.71; 95% CI, 0.50-1.01) than decaffeinated coffee (HR, 0.92; 95% CI, 0.55-1.54). There was no association between coffee consumption and ICC. Conclusions: These findings suggest that, in a U.S. population, coffee consumption is associated with reduced risk of HCC. Impact: Further research into specific coffee compounds and mechanisms that may account for these associations is needed. (C) 2015 AACR. C1 [Petrick, Jessica L.; Freedman, Neal D.; Graubard, Barry I.; Sahasrabuddhe, Vikrant V.; Alavanja, Michael C.; Beane-Freeman, Laura E.; Koshiol, Jill; Linet, Martha S.; Schairer, Catherine; Sigurdson, Alice J.; McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Lai, Gabriel Y.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Boggs, Deborah A.; Palmer, Julie R.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. [Buring, Julie E.; Chan, Andrew T.; Gaziano, John Michael; King, Lindsay Y.; Lee, I-Min; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Buring, Julie E.; Giovannucci, Edward L.; Lee, I-Min; Sesso, Howard D.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Chan, Andrew T.; King, Lindsay Y.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Chan, Andrew T.; Chong, Dawn Q.; King, Lindsay Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol, Boston, MA USA. [Fuchs, Charles S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Gapstur, Susan M.; Campbell, Peter T.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Hollenbeck, Albert R.] AARP, Washington, DC USA. [Poynter, Jenny N.] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. [Purdue, Mark P.] Ontario Inst Canc Res, Toronto, ON, Canada. [Robien, Kim] George Washington Univ, Milken Inst Sch Publ Hlth, Exercise & Nutr Sci, Washington, DC USA. [Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Dept Populat Hlth, New York, NY USA. [Wactawski-Wende, Jean] SUNY Buffalo, Dept Epidemiol & Environm Hlth, Buffalo, NY 14260 USA. RP Petrick, JL (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 7E-232, Bethesda, MD 20892 USA. EM jessica.petrick@nih.gov RI Purdue, Mark/C-9228-2016; Beane Freeman, Laura/C-4468-2015; OI Purdue, Mark/0000-0003-1177-3108; Beane Freeman, Laura/0000-0003-1294-4124; Robien, Kim/0000-0002-2120-2280; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303 FU NIH Intramural Research Program, NCI; NCI [CA39742, CA047988, HL043851, HL080467, HL099355, DK098311, CA186107, CA87969, CA167552] FX NIH Intramural Research Program, NCI (to J.L. Petrick, N.D. Freedman, B.I. Graubard, M.C. Alavanja, L.E. Beane-Freeman, J. Koshiol, M.S. Linet, M. Purdue, C. Schairer, A.J. Sigurdson, V.V. Sahasrabuddhe, and K.A. McGlynn). NCI Grants CA39742 (to J.N. Poynter and K. Robien), CA047988(to I.-M. Lee and J.E. Buring), HL043851 (to I.-M. Lee and J.E. Buring), HL080467 (to I.-M. Lee and J.E. Buring), HL099355(to I.-M. Lee and J.E. Buring), DK098311(to A.T. Chan), CA186107(to A.T. Chan), CA87969 (to A.T. Chan), and CA167552 (to A.T. Chan). NR 50 TC 4 Z9 4 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2015 VL 24 IS 9 BP 1398 EP 1406 DI 10.1158/1055-9965.EPI-15-0137 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CU3CK UT WOS:000363401000015 PM 26126626 ER PT J AU Luke, JJ Donahue, H Nishino, M Giobbie-Hurder, A Davis, M Bailey, N Ott, PA Hodi, FS AF Luke, Jason J. Donahue, Hilary Nishino, Mizuki Giobbie-Hurder, Anita Davis, Meredith Bailey, Nancy Ott, Patrick A. Hodi, F. Stephen TI Single Institution Experience of Ipilimumab 3 mg/kg with Sargramostim (GM-CSF) in Metastatic Melanoma SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID COLONY-STIMULATING FACTOR; GUIDELINE VERSION 1.1; BONE-MARROW CULTURES; RESPONSE CRITERIA; PROSTATE-CANCER; THERAPY; RECIST; IMMUNE; CELLS; TRIAL AB Ipilimumab, 10 mg/kg with sargramostim (GM-CSF; GM), improved overall survival (OS) and safety of patients with advanced melanoma over ipilimumab in a randomized phase II trial. The FDA-approved dose of ipilimumab of 3 mg/kg has not been assessed with GM (IPI-GM). Consecutive patients treated with IPI-GM at a single institution were reviewed. Treatment included ipilimumab every 3 weeks x 4 and GM, 250-mu g s.c. injection days 1 to 14 of each ipilimumab cycle. Efficacy, clinical characteristics, toxicities, and blinded radiology review of tumor burden were evaluated. Thirty-two patients were identified with 25 (78%) having immune-related response criteria (irRC) measurable disease and 41% with central nervous system metastases. A total of 88.6% of GM doses were administered. Response rate by irRC and disease control rate at 12 weeks were 20% and 44%, respectively (median follow-up 37 weeks). Immune-related adverse events (irAE) were observed in 10 (31.3%) patients, with 3 (9.4%) grade 3 events. Patients with grade 3 irAEs had prior autoimmunity, advanced age, and poor performance status. The median OS from first dose of ipilimumab was 41 weeks. Ipi-GM treatment is feasible and in this poor-risk advanced melanoma population, efficacy appeared similar but safety appeared improved relative to historical ipilimumab alone. (C) 2015 AACR. C1 [Luke, Jason J.] Univ Chicago, Sect Hematol Oncol, Dept Med, Chicago, IL 60637 USA. [Donahue, Hilary; Davis, Meredith; Bailey, Nancy; Ott, Patrick A.; Hodi, F. Stephen] Dana Farber Canc Inst, Melanoma Dis Ctr, Dept Med Oncol, Boston, MA 02115 USA. [Nishino, Mizuki] Dana Farber Brigham & Womens Canc Ctr, Dept Radiol, Boston, MA USA. [Nishino, Mizuki; Ott, Patrick A.; Hodi, F. Stephen] Harvard Univ, Sch Med, Boston, MA USA. [Giobbie-Hurder, Anita] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Luke, JJ (reprint author), Univ Chicago, 5841 South Maryland Ave,MC2115, Chicago, IL 60637 USA. EM jluke@medicine.bsd.uchicago.edu FU Paul Calabresi Career Development in Clinical Oncology Award [5K12CA139160]; NCI [1K23CA157631] FX J.J. Luke acknowledges funding from the Paul Calabresi Career Development in Clinical Oncology Award (5K12CA139160). M. Nishino was supported by 1K23CA157631 (NCI). NR 18 TC 5 Z9 5 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 SEP PY 2015 VL 3 IS 9 BP 986 EP 991 DI 10.1158/2326-6066.CIR-15-0066 PG 6 WC Oncology; Immunology SC Oncology; Immunology GA CU3EL UT WOS:000363406800003 PM 25943535 ER PT J AU Wang, L Amoozgar, Z Huang, J Saleh, MH Xing, DY Orsulic, S Goldberg, MS AF Wang, Lei Amoozgar, Zohreh Huang, Jing Saleh, Mohammad H. Xing, Deyin Orsulic, Sandra Goldberg, Michael S. TI Decitabine Enhances Lymphocyte Migration and Function and Synergizes with CTLA-4 Blockade in a Murine Ovarian Cancer Model SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID NK CELL REACTIVITY; REGULATORY T-CELLS; INTERFERON-GAMMA; IMMUNE-RESPONSE; EXPRESSION; MELANOMA; IMMUNOTHERAPY; LINES; CARCINOMA; THERAPY AB The lack of second-line treatment for relapsed ovarian cancer necessitates the development of improved combination therapies. Targeted therapy and immunotherapy each confer clinical benefit, albeit limited as monotherapies. Ovarian cancer is not particularly responsive to immune checkpoint blockade, so combination with a complementary therapy may be beneficial. Recent studies have revealed that a DNA methyl transferase inhibitor, azacytidine, alters expression of immunoregulatory genes in ovarian cancer. In this study, the antitumor effects of a related DNA methyl transferase inhibitor, decitabine (DAC), were demonstrated in a syngeneic murine ovarian cancer model. Low-dose DAC treatment increases the expression of chemokines that recruit NK cells and CD8(+) T cells, promotes their production of IFN gamma and TNF alpha, and extends the survival of mice bearing subcutaneous or orthotopic tumors. While neither DAC nor immune checkpoint blockade confers durable responses as a monotherapy in this model, the efficacy of anti-CTLA-4 was potentiated by combination with DAC. This combination promotes differentiation of naive T cells into effector T cells and prolongs cytotoxic lymphocyte responses as well as mouse survival. These results suggest that this combination therapy may be worthy of further consideration for improved treatment of drug-resistant ovarian cancer. (C) 2015 AACR. C1 [Wang, Lei; Amoozgar, Zohreh; Huang, Jing; Saleh, Mohammad H.; Goldberg, Michael S.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Xing, Deyin] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. [Orsulic, Sandra] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA. RP Goldberg, MS (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Michael_Goldberg1@dfci.harvard.edu OI Saleh, Mohammad H./0000-0001-8828-4367 FU Ovarian Cancer Research Fund (Liz Tilberis Scholar); Aid for Cancer Research; Kaleidoscope of Hope; Susan F. Smith Center for Women's Cancer FX This work was supported by the Ovarian Cancer Research Fund (Liz Tilberis Scholar), Aid for Cancer Research, Kaleidoscope of Hope, and the Susan F. Smith Center for Women's Cancer. NR 50 TC 12 Z9 12 U1 0 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 SEP PY 2015 VL 3 IS 9 BP 1030 EP 1041 DI 10.1158/2326-6066.CIR-15-0073 PG 12 WC Oncology; Immunology SC Oncology; Immunology GA CU3EL UT WOS:000363406800008 PM 26056145 ER PT J AU Morgan, TR Osann, K Bottiglieri, T Pimstone, N Hoefs, JC Hu, KQ Hassanein, T Boyer, TD Kong, L Chen, WP Richmond, E Gonzalez, R Rodriguez, LM Meyskens, FL AF Morgan, Timothy R. Osann, Kathryn Bottiglieri, Teodoro Pimstone, Neville Hoefs, John C. Hu, Ke-Qin Hassanein, Tarek Boyer, Thomas D. Kong, Lorene Chen, Wen-Pin Richmond, Ellen Gonzalez, Rachel Rodriguez, Luz M. Meyskens, Frank L. TI A Phase II Randomized, Controlled Trial of S-Adenosylmethionine in Reducing Serum alpha-Fetoprotein in Patients with Hepatitis C Cirrhosis and Elevated AFP SO CANCER PREVENTION RESEARCH LA English DT Article ID ADENOSYL-L-METHIONINE; RAT-LIVER CARCINOGENESIS; QUALITY-OF-LIFE; HEPATOCELLULAR-CARCINOMA; PRENEOPLASTIC LESIONS; PLASMA HOMOCYSTEINE; DNA METHYLATION; CLINICAL-TRIAL; RISK-FACTORS; DOUBLE-BLIND AB In animal models of hepatocellular carcinoma (HCC), deficiency of S-adenosylmethionine (SAMe) increased the risk of HCC whereas administration of SAMe reduced HCC. The aim of this trial was to determine whether oral SAMe administration to patients with hepatitis C cirrhosis would decrease serum alpha-fetoprotein (AFP) level, a biomarker of HCC risk in hepatitis C. This was a prospective, randomized, placebo-controlled, double-blind trial of SAMe, up to 2.4 g/d, for 24 weeks as compared with placebo among subjects with hepatitis C cirrhosis and a mildly elevated serum AFP. Primary outcome was change in AFP between baseline and week 24. Secondary outcomes included changes in routine tests of liver function and injury, other biomarkers of HCC risk, SAMe metabolites, markers of oxidative stress, and quality of life. One hundred ten subjects were randomized and 87 (44 SAMe and 43 placebo) completed treatment. There was no difference in the change in AFP during 24 weeks among subjects receiving SAMe as compared with placebo. Changes in markers of liver function, liver injury, and hepatitis C viral level were not significantly different between groups. Similarly, SAMe did not change markers of oxidative stress or serum glutathione level. SAMe blood level increased significantly among subjects receiving SAMe. Changes in quality of life did not differ between groups. Overall, this trial did not find that SAMe treatment improved serum AFP in subjects with advanced hepatitis C cirrhosis and a mildly elevated AFP. SAMe did not improve tests of liver function or injury or markers of oxidative stress or antioxidant potential. (C) 2015 AACR. C1 [Morgan, Timothy R.] VA Long Beach Healthcare Syst, Med Healthcare Grp, Long Beach, CA USA. [Morgan, Timothy R.; Hu, Ke-Qin] Univ Calif Irvine, Dept Med, Div Gastroenterol, Irvine, CA 92717 USA. [Osann, Kathryn] Univ Calif Irvine, Dept Med, Div Hematol Oncol, Irvine, CA 92717 USA. [Bottiglieri, Teodoro] Baylor Res Inst, Inst Metab Dis, Dallas, TX USA. [Pimstone, Neville] VA Greater Los Angeles Healthcare Syst, Med Healthcare Grp, Los Angeles, CA USA. [Hoefs, John C.; Meyskens, Frank L.] Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA. [Hassanein, Tarek] Univ Calif San Diego, Dept Med, Div Hepatol, San Diego, CA 92103 USA. [Boyer, Thomas D.] Univ Arizona, Liver Res Inst, Tucson, AZ USA. [Boyer, Thomas D.] Univ Arizona, Dept Med, Tucson, AZ USA. [Kong, Lorene] Univ Calif Irvine, Res Pharm, Irvine, CA USA. [Chen, Wen-Pin; Meyskens, Frank L.] Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Irvine, CA USA. [Richmond, Ellen; Rodriguez, Luz M.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Gonzalez, Rachel] VA Long Beach Healthcare Syst, Res Healthcare Grp, Long Beach, CA USA. [Rodriguez, Luz M.] Walter Reed Natl Mil Med Ctr, Dept Surg, Bethesda, MD USA. [Meyskens, Frank L.] Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92717 USA. [Meyskens, Frank L.] Univ Calif Irvine, Dept Publ Hlth, Irvine, CA USA. [Meyskens, Frank L.] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA. RP Morgan, TR (reprint author), VA Long Beach Healthcare Syst GI 11, 5901 East Seventh St, Long Beach, CA 90822 USA. EM timothy.morgan@va.gov FU NCI [N01-CN-35160]; National Center for Research Resources, NIH; National Center for Advancing Translational Sciences, NIH [UL1 TR000153] FX The study was supported by contract N01-CN-35160 from the NCI to F.L. Meyskens. The project described was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH, through Grant UL1 TR000153 to D.M. Cooper. NR 41 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 EI 1940-6215 J9 CANCER PREV RES JI Cancer Prev. Res. PD SEP PY 2015 VL 8 IS 9 BP 864 EP 872 DI 10.1158/1940-6207.CAPR-15-0029 PG 9 WC Oncology SC Oncology GA CU3BL UT WOS:000363398400013 PM 26130251 ER PT J AU Schnell, O Barnard, K Bergenstal, R Bosi, E Garg, S Guerci, B Haak, T Hirsch, IB Ji, LN Joshi, SR Kamp, M Laffel, L Mathieu, C Polonsky, WH Snoek, F Home, P AF Schnell, Oliver Barnard, Katharine Bergenstal, Richard Bosi, Emanuele Garg, Satish Guerci, Bruno Haak, Thomas Hirsch, Irl B. Ji, Linong Joshi, Sashank R. Kamp, Maarten Laffel, Lori Mathieu, Chantal Polonsky, William H. Snoek, Frank Home, Philip TI Clinical Utility of SMBG: Recommendations on the Use and Reporting of SMBG in Clinical Research SO DIABETES CARE LA English DT Article ID BLOOD-GLUCOSE; DIABETES-MELLITUS; CHRONIC HYPERGLYCEMIA; GLYCEMIC CONTROL; INSULIN; ADULTS; TRIAL; COMPLICATIONS; INTERVENTION; DYSGLYCEMIA C1 [Schnell, Oliver] Helmholtz Ctr Munich, Forscher Grp Diabet, Munich, Germany. [Barnard, Katharine] Univ Southampton, Southampton Gen Hosp, Southampton, Hants, England. [Bergenstal, Richard] Internat Diabet Ctr Pk Nicollet, Minneapolis, MN USA. [Bosi, Emanuele] Univ Vita Salute San Raffaele, Milan, Italy. [Garg, Satish] Univ Colorado, Dept Internal Med, Denver, CO 80202 USA. [Garg, Satish] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Guerci, Bruno] Ctr Hosp Univ Nancy, Vandoeuvre Les Nancy, France. [Haak, Thomas] Diabet Ctr Mergentheim, Bad Mergentheim, Germany. [Hirsch, Irl B.] Univ Washington, Sch Med, Seattle, WA USA. [Ji, Linong] Peking Univ, Dept Endocrinol & Metab, Peoples Hosp, Beijing, Peoples R China. [Joshi, Sashank R.] Indian Acad Diabet, Ahmadabad, Gujarat, India. [Kamp, Maarten] Queensland Univ Technol, Brisbane, Qld 4001, Australia. [Laffel, Lori] Joslin Diabet Ctr, Boston, MA 02215 USA. [Mathieu, Chantal] Univ Hosp Gasthuisberg Leuven, Leuven, Belgium. [Polonsky, William H.] Univ Calif San Diego, Behav Diabet Inst, San Diego, CA 92103 USA. [Snoek, Frank] Vrije Univ Amsterdam, Dept Med Psychol, Med Ctr, Amsterdam, Netherlands. [Snoek, Frank] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. [Home, Philip] Newcastle Univ, Inst Cellular Med Diabet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. RP Schnell, O (reprint author), Helmholtz Ctr Munich, Forscher Grp Diabet, Munich, Germany. EM oliver.schnell@lrz.uni-muenchen.de FU Roche Diagnostics Germany GmbH; Roche Diagnostics FX The medical writing of the manuscript was supported by an unrestricted research grant from Roche Diagnostics Germany GmbH. The idea to write the manuscript originates solely from the authors. None of the authors was compensated for writing the manuscript. O.S., K.B., R.B., E.B., S.G., B.G., T.H., I.B.H., L.J, S.R.J., M.K., L.L., CM., W.H.P., F.S., and P.H., or institutions with which they are associated, all receive funding from manufacturers of blood glucose monitoring systems, including Roche Diagnostics, for their advisory, lecturing, and/or research activities. No other potential conflicts of interest relevant to this article were reported. NR 44 TC 0 Z9 0 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2015 VL 38 IS 9 BP 1627 EP 1633 DI 10.2337/dc14-2919 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CU3HZ UT WOS:000363416500014 PM 26294772 ER PT J AU Silva, PS Cavallerano, JD Tolson, AM Rodriguez, J Rodriguez, S Ajlan, R Tolls, D Patel, B Sehizadeh, M Thakore, K Sun, JK Aiello, LP AF Silva, Paolo S. Cavallerano, Jerry D. Tolson, Ann M. Rodriguez, Jessica Rodriguez, Sashida Ajlan, Radwan Tolls, Dorothy Patel, Bina Sehizadeh, Mina Thakore, Komal Sun, Jennifer K. Aiello, Lloyd Paul TI Real-Time Ultrawide Field Image Evaluation of Retinopathy in a Diabetes Telemedicine Program SO DIABETES CARE LA English DT Article ID PHOTOGRAPHY AB OBJECTIVE To evaluate the ability of trained nonphysician retinal imagers to perform diabetic retinopathy (DR) evaluation at the time of ultrawide field retinal (UWF) imaging in a teleophthalmology program. RESEARCH DESIGN AND METHODS Clinic patients with diabetes received Joslin Vision Network protocol retinal imaging as part of their standard medical care. Retinal imagers evaluated UWF images for referable DR at the time of image capture. Training of the imagers included 4 h of standardized didactic lectures and 12 h of guided image review. Real-time evaluations were compared with standard masked gradings performed at a centralized reading center. RESULTS A total of 3,978 eyes of 1,989 consecutive patients were imaged and evaluated. By reading center evaluation, 3,769 eyes (94.7%) were gradable for DR, 1,376 (36.5%) had DR, and 580 (15.3%) had referable DR. Compared with the reading center, real-time image evaluation had a sensitivity and specificity for identifying more than minimal DR of 0.95 (95% CI 0.94-0.97) and 0.84 (0.82-0.85), respectively, and 0.99 (0.97-1.00) and 0.76 (0.75-0.78), respectively, for detecting referable DR. Only three patients with referable DR were not identified by imager evaluation. CONCLUSIONS Point-of-care evaluation of UWF images by nonphysician imagers following standardized acquisition and evaluation protocols within an established teleophthalmology program had good sensitivity and specificity for detection of DR and for identification of referable retinal disease. With immediate image evaluation, <0.1% of patients with referable DR would be missed, reading center image grading burden would be reduced by 60%, and patient feedback would be expedited. C1 [Silva, Paolo S.; Cavallerano, Jerry D.; Tolson, Ann M.; Rodriguez, Jessica; Rodriguez, Sashida; Ajlan, Radwan; Tolls, Dorothy; Patel, Bina; Sehizadeh, Mina; Thakore, Komal; Sun, Jennifer K.; Aiello, Lloyd Paul] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. [Silva, Paolo S.; Cavallerano, Jerry D.; Sun, Jennifer K.; Aiello, Lloyd Paul] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Silva, Paolo S.] Univ Philippines, Teleophthalmol & Image Reading Ctr, Philippine Eye Res Inst, Natl Inst Hlth, Manila, Philippines. [Patel, Bina] New England Coll Optometry, Boston, MA USA. RP Silva, PS (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. EM paoloantonio.silva@joslin.harvard.edu FU Center of Integration of Medicine and Innovative Technology FX The study was supported by grant funding from the Center of Integration of Medicine and Innovative Technology to P.S.S. JVN technology was developed at the Joslin Diabetes Center. All the authors were employees of the Joslin Diabetes Center at the time the study was conducted. NR 17 TC 6 Z9 7 U1 0 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2015 VL 38 IS 9 BP 1643 EP 1649 DI 10.2337/dc15-0161 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CU3HZ UT WOS:000363416500017 PM 26033507 ER PT J AU Mellati, M Eaton, KD Brooks-Worrell, BM Hagopian, WA Martins, R Palmer, JP Hirsch, IB AF Mellati, Mahnaz Eaton, Keith D. Brooks-Worrell, Barbara M. Hagopian, William A. Martins, Renato Palmer, Jerry P. Hirsch, Irl B. TI Anti-PD-1 and Anti-PDL-1 Monoclonal Antibodies Causing Type 1 Diabetes SO DIABETES CARE LA English DT Letter C1 [Mellati, Mahnaz; Brooks-Worrell, Barbara M.; Hagopian, William A.; Palmer, Jerry P.; Hirsch, Irl B.] Univ Washington, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Eaton, Keith D.; Martins, Renato] Univ Washington, Dept Med Oncol, Seattle, WA 98195 USA. [Brooks-Worrell, Barbara M.; Palmer, Jerry P.] VA Puget Sound Hlth Care Syst, Div Endocrinol, Seattle, WA USA. [Hagopian, William A.] Pacific Northwest Diabet Res Inst, Seattle, WA USA. RP Hirsch, IB (reprint author), Univ Washington, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. EM ihirsch@uw.edu NR 5 TC 10 Z9 10 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2015 VL 38 IS 9 BP E137 EP E138 DI 10.2337/dc15-0889 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CU3HZ UT WOS:000363416500004 PM 26116720 ER PT J AU Silver, FL Salinas, J Sprinkhuizen, SM Schwamm, LH AF Silver, F. L. Salinas, J. Sprinkhuizen, S. M. Schwamm, L. H. TI Defining an international standard set of patient-centered outcome measures after stroke SO INTERNATIONAL JOURNAL OF STROKE LA English DT Meeting Abstract C1 [Silver, F. L.] Univ Toronto, Ontario Stroke Registry, Toronto, ON, Canada. [Salinas, J.; Sprinkhuizen, S. M.] Int Consortium Hlth Outcomes Measurement, Cambridge, MA USA. [Salinas, J.; Schwamm, L. H.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD SEP PY 2015 VL 10 SU 4 SI SI MA O5.4 BP 15 EP 15 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CU2DZ UT WOS:000363334400036 ER PT J AU Jeong, HS Jones, D Liao, S Wattson, DA Cui, CH Duda, DG Willett, CG Jain, RK Padera, TP AF Jeong, Han-Sin Jones, Dennis Liao, Shan Wattson, Daniel A. Cui, Cheryl H. Duda, Dan G. Willett, Christopher G. Jain, Rakesh K. Padera, Timothy P. TI Investigation of the Lack of Angiogenesis in the Formation of Lymph Node Metastases SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PRIMARY TUMOR; INDUCED LYMPHANGIOGENESIS; RANDOMIZED-TRIAL; DENDRITIC CELLS; RECTAL-CANCER; BREAST-CANCER; COLON-CANCER; VEGF; BEVACIZUMAB; CARCINOMA AB Background: To date, antiangiogenic therapy has failed to improve overall survival in cancer patients when used in the adjuvant setting (local-regional disease with no detectable systemic metastasis). The presence of lymph node metastases worsens prognosis, however their reliance on angiogenesis for growth has not been reported. Methods: Here, we introduce a novel chronic lymph node window (CLNW) model to facilitate new discoveries in the growth and spread of lymph node metastases. We use the CLNW in multiple models of spontaneous lymphatic metastases in mice to study the vasculature of metastatic lymph nodes (n = 9-12). We further test our results in patient samples (n = 20 colon cancer patients; n = 20 head and neck cancer patients). Finally, we test the ability of antiangiogenic therapy to inhibit metastatic growth in the CLNW. All statistical tests were two-sided. Results: Using the CLNW, we reveal the surprising lack of sprouting angiogenesis during metastatic growth, despite the presence of hypoxia in some lesions. Treatment with two different antiangiogenic therapies showed no effect on the growth or vascular density of lymph node metastases (day 10: untreated mean = 1.2%, 95% confidence interval [CI] = 0.7% to 1.7%; control mean = 0.7%, 95% CI = 0.1% to 1.3%; DC101 mean = 0.4%, 95% CI = 0.0% to 3.3%; sunitinib mean = 0.5%, 95% CI = 0.0% to 1.0%, analysis of variance P = .34). We confirmed these findings in clinical specimens, including the lack of reduction in blood vessel density in lymph node metastases in patients treated with bevacizumab (no bevacizumab group mean = 257 vessels/mm(2), 95% CI = 149 to 365 vessels/mm(2); bevacizumab group mean = 327 vessels/mm(2), 95% CI = 140 to 514 vessels/mm(2), P = .78). Conclusion: We provide preclinical and clinical evidence that sprouting angiogenesis does not occur during the growth of lymph node metastases, and thus reveals a new mechanism of treatment resistance to antiangiogenic therapy in adjuvant settings. The targets of clinically approved angiogenesis inhibitors are not active during early cancer progression in the lymph node, suggesting that inhibitors of sprouting angiogenesis as a class will not be effective in treating lymph node metastases. C1 [Jeong, Han-Sin; Jones, Dennis; Liao, Shan; Wattson, Daniel A.; Cui, Cheryl H.; Duda, Dan G.; Jain, Rakesh K.; Padera, Timothy P.] Massachusetts Gen Hosp, MGH Canc Ctr, Dept Radiat Oncol, Edwin L Steele Labs, Boston, MA 02114 USA. [Jeong, Han-Sin; Jones, Dennis; Liao, Shan; Wattson, Daniel A.; Cui, Cheryl H.; Duda, Dan G.; Jain, Rakesh K.; Padera, Timothy P.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Jeong, Han-Sin] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, Seoul, South Korea. [Willett, Christopher G.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC USA. RP Padera, TP (reprint author), Massachusetts Gen Hosp, MGH Canc Ctr, Dept Radiat Oncol, Edwin L Steele Labs, 100 Blossom St, Boston, MA 02114 USA. EM tpadera@steele.mgh.harvard.edu RI Jeong, Han Sin/F-4597-2014 FU National Institute of Health [DP2OD008780, R00CA137167]; National Cancer Institute (NCI) [C06 CA059267, P01 CA080124, R01-CA159258]; US Department of Defense CDMRP [W81XWH-10-1-0016]; National Foundation for Cancer Research; American Cancer Society [120733-RSG-11-073-01-TBG]; Korean MEST [NRF-2012R1A1A2040866]; Samsung Biomedical Research Institute [GL1B22912]; United Negro College Fund-Merck Science Initiative Postdoctoral Fellowship; Burroughs Wellcome Postdoctoral Enrichment Program Award; National Institutes of Health (NIH) [NCI F32CA183465]; Charles A. King Trust Fellowship; NIH [K99HL111343-01A1] FX This work was supported by the National Institute of Health DP2OD008780 (TPP), R00CA137167 (TPP), National Cancer Institute (NCI) Federal Share/MGH Proton Beam Income on C06 CA059267 (TPP, RKJ), P01 CA080124 (RKJ), and R01-CA159258 (DGD). This work was also supported in part by the US Department of Defense CDMRP W81XWH-10-1-0016 (RKJ), the National Foundation for Cancer Research (RKJ), American Cancer Society grant 120733-RSG-11-073-01-TBG (DGD), Korean MEST NRF-2012R1A1A2040866 (HJ), Samsung Biomedical Research Institute Grant #GL1B22912 (HJ), United Negro College Fund-Merck Science Initiative Postdoctoral Fellowship (DJ), Burroughs Wellcome Postdoctoral Enrichment Program Award (DJ), National Institutes of Health (NIH) NCI F32CA183465 (DJ), Charles A. King Trust Fellowship (SL) and NIH K99HL111343-01A1 (SL). NR 53 TC 12 Z9 12 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD SEP PY 2015 VL 107 IS 9 AR djv155 DI 10.1093/jnci/djv155 PG 11 WC Oncology SC Oncology GA CU0KA UT WOS:000363203800018 ER PT J AU Ligibel, JA Cirrincione, CT Liu, M Citron, M Ingle, JN Gradishar, W Martino, S Sikov, W Michaelson, R Mardis, E Perou, CM Ellis, M Winer, E Hudis, CA Berry, D Barry, WT AF Ligibel, Jennifer A. Cirrincione, Constance T. Liu, Minetta Citron, Marc Ingle, James N. Gradishar, William Martino, Silvana Sikov, William Michaelson, Richard Mardis, Elaine Perou, Charles M. Ellis, Matthew Winer, Eric Hudis, Clifford A. Berry, Donald Barry, William T. TI Body Mass Index, PAM50 Subtype, and Outcomes in Node-Positive Breast Cancer: CALGB 9741 (Alliance) SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CHEMOTHERAPY; SURVIVAL; INSULIN; WOMEN; RISK AB Background: Obesity at diagnosis is associated with poor prognosis in women with breast cancer, but few reports have been adjusted for treatment factors. Methods: CALGB 9741 was a randomized trial of dose density and sequence of chemotherapy for node-positive breast cancer. All patients received doxorubicin, cyclophosphamide, and paclitaxel, dosed by actual body weight. Height and weight at diagnosis were abstracted from patient records, and the PAM50 assay was performed from archived specimens using the NanoString platform. Relationships between body mass index (BMI), PAM50, and recurrence-free and overall survival (RFS and OS) were evaluated using proportional hazards regression, adjusting for number of involved nodes, estrogen receptor (ER) status, tumor size, menopausal status, drug sequence, and dose density. All statistical tests were two-sided. Results: Baseline height and weight were available for 1909 of 2005 enrolled patients; 1272 additionally had subtype determination by PAM50. Median baseline BMI was 27.4 kg/m(2). After 11 years of median follow-up, there were 619 RFS events and 543 deaths. Baseline BMI was a statistically significant predictor of RFS (adjusted hazard ratio [HR] for each five-unit increase in BMI = 1.08, 95% confidence interval [CI] = 1.02 to 1.14, P = .01) and OS (adjusted HR = 1.08, 95% CI = 1.01 to 1.14, P = .02) BMI and molecular phenotypes were independent prognostic factors for RFS, with no statistically significant interactions detected. Conclusions: BMI at diagnosis was a statistically significant prognostic factor in a group of patients receiving optimally dosed chemotherapy. Additional research is needed to determine the impact of weight loss on breast cancer outcomes and to evaluate whether this impact is maintained across tumor subtypes. C1 [Ligibel, Jennifer A.; Winer, Eric] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cirrincione, Constance T.] Alliance Stat & Data Ctr, Durham, NC USA. [Liu, Minetta; Ingle, James N.] Mayo Clin, Rochester, MN USA. [Citron, Marc] ProHEALTH Care Associates, Lake Success, NY USA. [Gradishar, William] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Martino, Silvana] Angeles Clin & Res Inst, Santa Monica, CA USA. [Sikov, William] Rhode Isl Hosp, Providence, RI USA. [Michaelson, Richard] St Barnabas Hosp, Livingston, NJ USA. [Mardis, Elaine] Washington Univ, Genome Inst, St Louis, MO USA. [Perou, Charles M.] Univ N Carolina, Lineberger Canc Ctr, Dept Genet, Chapel Hill, NC USA. [Ellis, Matthew] Siteman Canc Ctr, Breast Canc Program, St Louis, MO USA. [Ellis, Matthew] Washington Univ, Sch Med, St Louis, MO USA. [Hudis, Clifford A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Berry, Donald] Univ Texas Houston, MD Anderson Canc Ctr, Alliance Stat & Data Ctr, Houston, TX 77030 USA. [Barry, William T.] Dana Farber Canc Inst, Alliance Stat & Data Ctr, Boston, MA 02115 USA. RP Ligibel, JA (reprint author), 450 Brookline Ave,Yawkey 1234, Boston, MA 02215 USA. EM jligibel@partners.org OI Perou, Charles/0000-0001-9827-2247 FU Breast Cancer Research Foundation; National Cancer Institute Strategic Partnering To Evaluate Cancer Signatures (SPECS) Program [U01-CA114722]; National Cancer Institute [CA31946]; Alliance Statistics and Data Center [CA33601]; North Central Cancer Treatment Group (NCCTG) [CA025224]; Eastern Cooperative Oncology Group (ECOG) [CA21115, CA17145]; Southwestern Oncology Group (SWOG) [CA32102] FX This work was supported by funding from the Breast Cancer Research Foundation, the National Cancer Institute Strategic Partnering To Evaluate Cancer Signatures (SPECS) Program (U01-CA114722 to ME, CP, and EM), and by grants from the National Cancer Institute to the Alliance for Clinical Trials in Oncology (Monica M. Bertagnolli, MD, Chair; CA31946), the Alliance Statistics and Data Center (Daniel J. Sargent, PhD; CA33601), North Central Cancer Treatment Group (NCCTG) (CA025224), Eastern Cooperative Oncology Group (ECOG) (CA21115 and CA17145), and Southwestern Oncology Group (SWOG) (CA32102). NR 20 TC 1 Z9 1 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD SEP PY 2015 VL 107 IS 9 AR djv179 DI 10.1093/jnci/djv179 PG 7 WC Oncology SC Oncology GA CU0KA UT WOS:000363203800019 ER PT J AU Lin, CC Gray, PJ Jemal, A Efstathiou, JA AF Lin, Chun Chieh Gray, Phillip J. Jemal, Ahmedin Efstathiou, Jason A. TI Untitled RESPONSE SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID POSITIVE PROSTATE-CANCER; LYMPH-NODE DISSECTION; RADICAL PROSTATECTOMY; SURVIVAL; THERAPY; IMPACT C1 [Lin, Chun Chieh; Jemal, Ahmedin] Amer Canc Soc, Intramural Res, Surveillance & Hlth Serv Res Program, Atlanta, GA 30329 USA. [Gray, Phillip J.; Efstathiou, Jason A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. RP Efstathiou, JA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM jefstathiou@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 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD SEP PY 2015 VL 107 IS 9 AR djv201 DI 10.1093/jnci/djv201 PG 1 WC Oncology SC Oncology GA CU0KA UT WOS:000363203800020 ER PT J AU Shen, ZL Feng, Y Sheh, A Everitt, J Bertram, F Paster, BJ Fox, JG AF Shen, Zeli Feng, Yan Sheh, Alexander Everitt, Jeffrey Bertram, Frederick Paster, Bruce J. Fox, James G. TI Isolation and characterization of a novel Helicobacter species, Helicobacter jaachi sp nov., from common marmosets (Callithrix jaachus) SO JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article ID CHRONIC IDIOPATHIC COLITIS; TAMARINS SAGUINUS-OEDIPUS; HEPATICUS INFECTION; RHESUS-MONKEYS; INTESTINAL ADENOCARCINOMA; CAMPYLOBACTER-FENNELLIAE; HOMOSEXUAL MEN; A/JCR MICE; JACCHUS; CINAEDI AB Purpose-bred common marmosets from domestic sources housed in a US research facility, and used in multiple drug discovery programmes, were noted to have a high incidence of spontaneous inflammatory bowel disease and sporadic cholecystitis. and cholangiohepatitis. Inflammatory infiltrates increased in incidence and severity with age. Because Helicobacter spp. have been linked to gastrointestinal diseases, samples from the gastrointestinal tracts of 39 marmosets were screened for Helicobacter spp. by culture and PCR. Helicobacter spp. were frequently detected in marmosets; 28.2 % of the marmosets were positive for a proposed novel species, Helicobacter jaachi sp. nov., by culture, and 48.7 % were positive by Helicobacter genus-specific PCR. Seventeen strains of Helicobacter sp. from 11 marmosets were cultured from various gastrointestinal sites. Older animals (age 6-11 years) had a higher helicobacter prevalence rate (57.1 %) compared with younger animals (age 3-5 years), which had a 27.2 % prevalence rate. Cells of H. jaachi sp. nov. were catalase, urease and oxidase positive and had fusiform morphology, with periplasnnic fibres and multiple bipolar, sheathed flagella. All isolates had similar 16S and 23S rRNA sequences, which clustered as representatives of a novel Helicobacter species closely related to 'Helicobacter sanguini' (97 %), a species isolated from cotton-top tamarins and 'Helicobacter callitrichis' (96 %) isolated previously from the faeces of common marmosets. The whole genome sequence of one of the liver isolates, H. jaachi sp. nov. MIT 09-6949(T), had a 1.9 Mb genome length with a 41 mol% DNA G+C content. The type strain of Helicobacter jaachi sp. nov., MIT 09-6949(T), has been deposited in the BCCM/LMG Bacteria Collection as LMG 28613(T). These findings add to the increasing number of animal species with gastrointestinal disease in which novel enterohepatic Helicobacter spp. have been isolated. C1 [Shen, Zeli; Feng, Yan; Sheh, Alexander; Fox, James G.] MIT, Div Comparat Med, Cambridge, MA 02139 USA. [Everitt, Jeffrey; Bertram, Frederick] GlaxoSmithKline, Res Triangle Pk, NC USA. [Paster, Bruce J.] Forsyth Inst, Cambridge, MA USA. RP Fox, JG (reprint author), MIT, Div Comparat Med, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM jgfox@mit.edu OI Everitt, Jeffrey/0000-0003-0273-6284 FU NIH [P30-ES002109, RO1-OD011141, T32-OD0010978] FX We thank Hans Truper for providing taxonomic expertise in naming of this novel Helicobacter species and Alyssa Terestre for her assistance in preparing this manuscript. Supported by NIH P30-ES002109 (J. G. F.), RO1-OD011141 (J. G. F.) and T32-OD0010978 (J. G. F.) NR 42 TC 2 Z9 2 U1 1 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-2615 EI 1473-5644 J9 J MED MICROBIOL JI J. Med. Microbiol. PD SEP PY 2015 VL 64 BP 1063 EP 1073 DI 10.1099/jmm.0.000113 PN 9 PG 11 WC Microbiology SC Microbiology GA CU2ME UT WOS:000363356800017 PM 26297446 ER PT J AU Koelman, DLH Mateen, FJ AF Koelman, Diederik L. H. Mateen, Farrah J. TI Acute disseminated encephalomyelitis: current controversies in diagnosis and outcome SO JOURNAL OF NEUROLOGY LA English DT Review DE Acute disseminated encephalomyelitis; Autoimmune diseases; Encephalopathy; Postinfectious ID PEDIATRIC MULTIPLE-SCLEROSIS; TERM-FOLLOW-UP; MULTIPHASIC DISSEMINATED ENCEPHALOMYELITIS; MYELIN OLIGODENDROCYTE GLYCOPROTEIN; CNS INFLAMMATORY DEMYELINATION; NEUROMYELITIS-OPTICA; PROGNOSTIC-FACTORS; CLINICAL-FEATURES; EARLY RELAPSE; CHILDREN AB Acute disseminated encephalomyelitis (ADEM) is a rare inflammatory, demyelinating disorder of the CNS. Only in the past 15 years have larger groups of patients from several geographical areas been reported for comparisons across studies. In spite of the increased recognition of ADEM, the diagnosis of ADEM remains clinical, aided by neuroimaging confirmation, because of the lack of a biological marker. The diagnosis may be difficult, given that several diseases may present similar to ADEM. The controversial existence of multiphasic forms necessitates a continuous evaluation of the diagnosis by tracking subsequent events. Despite proposed consensus criteria, the diagnostic criteria employed to characterize ADEM range widely among the largest reported cohorts to date. This review comprehensively evaluates the current knowledge and controversies that surround ADEM, with special consideration of the distinction between ADEM and other demyelinating diseases such as multiple sclerosis. In addition, we present implications of the current knowledge of ADEM for both research and clinical practice. C1 [Koelman, Diederik L. H.; Mateen, Farrah J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Koelman, Diederik L. H.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. [Mateen, Farrah J.] Harvard Univ, Sch Med, Boston, MA USA. RP Mateen, FJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, 165 Cambridge St 627, Boston, MA 02114 USA. EM dlhkoelman@gmail.com; fmateen@partners.org NR 82 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5354 EI 1432-1459 J9 J NEUROL JI J. Neurol. PD SEP PY 2015 VL 262 IS 9 BP 2013 EP 2024 DI 10.1007/s00415-015-7694-7 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA CT7ZV UT WOS:000363035400002 PM 25761377 ER PT J AU Jick, SS Li, L Falcone, GJ Vassilev, ZP Wallander, MA AF Jick, Susan S. Li, L. Falcone, G. J. Vassilev, Z. P. Wallander, M. -A. TI Epidemiology of multiple sclerosis: results from a large observational study in the UK SO JOURNAL OF NEUROLOGY LA English DT Article DE Multiple sclerosis; Epidemiology; Cohort Analysis; Mortality ID PRACTICE RESEARCH DATABASE; UNITED-KINGDOM; VITAMIN-D; RISK; MORTALITY; TRIAL; MULTICENTER; VALIDATION; VALIDITY; DISEASE AB Multiple sclerosis (MS) progression to mortality may not be solely determined by the underlying autoimmune process. We conducted a study in a large cohort of MS patients with the aim of describing characteristics of MS patients and identification of predictors for all-cause mortality in this patient group. We performed a retrospective analysis of primary care data from the UK Clinical Practice Research Datalink. Incident MS cases diagnosed between 1993 and 2006 were identified and validated using electronic and original medical records. Patients were followed to identify deaths; hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated using Cox proportional regression with age as time-scale. In total, 1713 incident MS cases were identified. Following MS diagnosis, frequent comorbidities were infections (80 %), and depression (46 %). Adjusted HRs (95 % CIs) for all-cause mortality were: 2.0 (1.2-3.4) for current smoking; 7.6 (3.2-17.7) for alcohol abuse; 2.7 (1.6-4.5) for pneumonia and influenza; 4.1 (2.7-6.3) for urinary tract infections; 2.2 (1.2-4.2) for heart disease and 4.9 (2.9-8.0) for cancer. Our results suggest that MS survival is influenced not only by the underlying autoimmune process, but also by patient comorbidities and lifestyle factors. C1 [Jick, Susan S.; Li, L.] Boston Univ, BCDSP, Sch Publ Hlth, Lexington, MA 02421 USA. [Falcone, G. J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Vassilev, Z. P.] Bayer Healthcare Pharmaceut, Whippany, NJ USA. [Wallander, M. -A.] Uppsala Univ, Dept Publ Hlth & Caring Sci, Uppsala, SE, Sweden. RP Jick, SS (reprint author), Boston Univ, BCDSP, Sch Publ Hlth, 11 Muzzey St, Lexington, MA 02421 USA. EM sjick@bu.edu RI Falcone, Guido/L-2287-2016; CPRD, CPRD/B-9594-2017 OI Falcone, Guido/0000-0002-6407-0302; FU Bayer Healthcare AG FX This study was funded by Bayer Healthcare AG. We thank Susan Bromley, Independent Medical Writer (Oxford, UK) for assistance in the drafting and editing the manuscript. This study is based on data from the Full Feature GPRD GOLD database obtained under licence from the UK Medicines and Healthcare Products Regulatory Agency. NR 28 TC 6 Z9 6 U1 1 U2 8 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5354 EI 1432-1459 J9 J NEUROL JI J. Neurol. PD SEP PY 2015 VL 262 IS 9 BP 2033 EP 2041 DI 10.1007/s00415-015-7796-2 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA CT7ZV UT WOS:000363035400004 PM 26067217 ER PT J AU Friedman, D Masek, B Barreto, E Baer, L Lapey, A Budge, E McQuaid, EL AF Friedman, Deborah Masek, Bruce Barreto, Esteban Baer, Lee Lapey, Allen Budge, Eduardo McQuaid, Elizabeth L. TI Fathers and Asthma Care: Paternal Involvement, Beliefs, and Management Skills SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Article DE adherence; asthma; co-parenting; fathers; paternal; pediatric; quality of life ID PEDIATRIC CHRONIC DISEASES; QUALITY-OF-LIFE; MEDICATION ADHERENCE; CHILDREN; ASSOCIATIONS; BARRIERS; OUTCOMES; INHALER; PARENTS; ILLNESS AB Objective To compare asthma care roles of maternal and paternal caregivers, and examine associations between caregiver involvement and the outcomes of adherence, morbidity, and parental quality of life (QoL). Methods Mothers and fathers in 63 families of children, ages 5-9 years, with persistent asthma completed semistructured interviews and questionnaires. Adherence was measured via electronic monitoring. Paired t tests compared parental asthma care roles, and analysis of covariance, controlling for socioeconomic status, evaluated associations of asthma outcomes with caregiver involvement scores. Results Mothers had higher scores on measures of involvement, beliefs in medication necessity, and on four subscales of the Family Asthma Management System Scale interview (Asthma Knowledge, Relationship with Provider, Symptom Assessment, and Response to Symptoms). Maternal QoL was lowest when both maternal and paternal involvement was high. Paternal involvement was associated with increased morbidity. Conclusions There is room for enhancement of fathers' asthma care roles. Higher levels of paternal involvement may be driven by family need. C1 [Friedman, Deborah; Masek, Bruce; Baer, Lee; Lapey, Allen; Budge, Eduardo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Barreto, Esteban] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McQuaid, Elizabeth L.] Brown Med Sch, Bradley Hasbro Childrens Res Ctr, Providence, RI USA. RP Friedman, D (reprint author), Massachusetts Gen Hosp, Dept Child & Adolescent Psychiat, 55 Fruit St,Yaw 6a, Boston, MA 02132 USA. EM dfriedman@partners.org FU Eunice Kennedy Shriver National Institute for Child Health and Development [R03 HD055322-01A2] FX Funds for this study were provided by grant (R03 HD055322-01A2 to D.F.) from the Eunice Kennedy Shriver National Institute for Child Health and Development. NR 34 TC 0 Z9 0 U1 2 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-8693 EI 1465-735X J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD SEP PY 2015 VL 40 IS 8 BP 768 EP 780 DI 10.1093/jpepsy/jsv035 PG 13 WC Psychology, Developmental SC Psychology GA CU0NX UT WOS:000363215200006 PM 25922295 ER PT J AU Muram, D Zhang, X Cui, ZL Matsumoto, AM AF Muram, David Zhang, Xiang Cui, Zhanglin Matsumoto, Alvin M. TI Use of Hormone Testing for the Diagnosis and Evaluation of Male Hypogonadism and Monitoring of Testosterone Therapy: Application of Hormone Testing Guideline Recommendations in Clinical Practice SO JOURNAL OF SEXUAL MEDICINE LA English DT Article DE Hypogonadism; Testosterone; Hormone Testing; Retrospective Study ID SERUM TESTOSTERONE; MEN; DEFICIENCY AB Introduction. Clinical practice guidelines recommend that testosterone (T) levels be measured on >= 2 occasions to confirm a diagnosis of hypogonadism, gonadotropins be measured to determine whether hypogonadism is primary or secondary, and T levels be measured to monitor the adequacy of T therapy. However, it is not known whether hormone testing as recommended by guidelines is routinely performed in real-world clinical practice. Aim. The aim of this study was to assess the use of hormone testing for the diagnosis and evaluation of hypogonadism and monitoring of T therapy in clinical practice. Methods. In this retrospective cohort study of the Truven Health Marketscan (R) Commercial and Medicare Supplemental Insurance Databases during 2010-2012, 63,534 men over 18 years old who received T therapy and had continuous medical benefit enrollment for 1 year prior to and 6 months after T therapy initiation were included in this analysis. Main Outcome Measures. Proportion of patients who received >= 2, 1, or no T-level determinations prior to or following T therapy initiation. Results. Seventy-one percent of hypogonadal men had T measured at least once and 40% had >= 2 tests, but only 12% of men had luteinizing hormone and/or follicle-stimulating hormone levels measured prior to T therapy initiation. Following T therapy initiation, 46% had >= 1 follow-up T measurements. Conclusions. Appropriate use of T and gonadotropin levels in clinical practice as recommended by guidelines is suboptimal, increasing the possibility of overdiagnosis of male hypogonadism, underdiagnosis of secondary hypogonadism, and inappropriate T therapy use and management. Further investigation is needed into reasons for nonadherence to guidelines for appropriate hormone testing to inform future quality improvement efforts. C1 [Muram, David; Zhang, Xiang; Cui, Zhanglin] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. [Matsumoto, Alvin M.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Matsumoto, Alvin M.] Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Muram, D (reprint author), Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. EM muram_david@lilly.com FU Eli Lilly and Company FX This work was sponsored by Eli Lilly and Company. DM, XZ, and ZC are employees and minor shareholders of Eli Lilly and Company. Dr. Matsumoto has served as a consultant for Eli Lilly and Company. NR 17 TC 6 Z9 6 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-6095 EI 1743-6109 J9 J SEX MED JI J. Sex. Med. PD SEP PY 2015 VL 12 IS 9 BP 1886 EP 1894 DI 10.1111/jsm.12968 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA CU3WJ UT WOS:000363456400005 PM 26272690 ER PT J AU Lawrenson, K Li, Q Kar, S Seo, JH Tyrer, J Spindler, TJ Lee, J Chen, Y Karst, A Drapkin, R Aben, KKH Anton-Culver, H Antonenkova, N Baker, H Bandera, EV Bean, Y Beckmann, MW Berchuck, A Bisogna, M Bjorge, L Bogdanova, N Brinton, LA Brooks-Wilson, A Bruinsma, F Butzow, R Campbell, IG Carty, K Chang-Claude, J Chenevix-Trench, G Chen, A Chen, Z Cook, LS Cramer, DW Cunningham, JM Cybulski, C Dansonka-Mieszkowska, A Dennis, J Dicks, E Doherty, JA Doerk, T Du Bois, A Duerst, M Eccles, D Easton, DT Edwards, RP Eilber, U Ekici, AB Fasching, PA Fridley, BL Gao, YT Gentry-Maharaj, A Giles, GG Glasspool, R Goode, EL Goodman, MT Grownwald, J Harrington, P Harter, P Hasmad, HN Hein, A Heitz, F Hildebrandt, MAT Hillemanns, P Hogdall, E Hogdall, C Hosono, S Iversen, ES Jakubowska, A James, P Jensen, A Ji, BT Karlan, BY Kjaer, SK Kelemen, LE Kellar, M Kelley, JL Kiemeney, LA Krakstad, C Kupryjanczyk, J Lambrechts, D Lambrechts, S Le, ND Lee, AW Lele, S Leminen, A Lester, J Levine, DA Liang, D Lissowska, J Lu, K Lubinski, J Lundvall, L Massuger, LFAG Matsuo, K McGuire, V McLaughlin, JR Nevanlinna, H McNeish, I Menon, U Modugno, F Moysich, KB Narod, SA Nedergaard, L Ness, RB Azmi, MAN Odunsi, K Olson, SH Orlow, I Orsulic, S Weber, RP Pearce, CL Pejovic, T Pelttari, LM Permuth-Wey, J Phelan, CM Pike, MC Poole, EM Ramus, SJ Risch, HA Rosen, B Rossing, MA Rothstein, JH Rudolph, A Runnebaum, IB Rzepecka, IK Salvesen, HB Schildkraut, JM Schwaab, I Sellers, TA Shu, XO Shvetsov, YB Siddiqui, N Sieh, W Song, H Southey, MC Sucheston, L Tangen, IL Teo, SH Terry, KL Thompson, PJ Timorek, A Tsai, YY Tworoger, SS Van Altena, AM Van Nieuwenhuysen, E Vergote, I Vierkant, RA Wang-Gohrke, S Walsh, C Wentzensen, N Whittemore, AS Wicklund, KG Wilkens, LR Woo, YL Wu, X Wu, AH Yang, H Zheng, W Ziogas, A Monteiro, A Pharoah, PD Gayther, SA Freedman, ML Grp, AOCS Bowtell, D Webb, PM Defazio, A AF Lawrenson, Kate Li, Qiyan Kar, Siddhartha Seo, Ji-Heui Tyrer, Jonathan Spindler, Tassja J. Lee, Janet Chen, Yibu Karst, Alison Drapkin, Ronny Aben, Katja K. H. Anton-Culver, Hoda Antonenkova, Natalia Baker, Helen Bandera, Elisa V. Bean, Yukie Beckmann, Matthias W. Berchuck, Andrew Bisogna, Maria Bjorge, Line Bogdanova, Natalia Brinton, Louise A. Brooks-Wilson, Angela Bruinsma, Fiona Butzow, Ralf Campbell, Ian G. Carty, Karen Chang-Claude, Jenny Chenevix-Trench, Georgia Chen, Anne Chen, Zhihua Cook, Linda S. Cramer, Daniel W. Cunningham, Julie M. Cybulski, Cezary Dansonka-Mieszkowska, Agnieszka Dennis, Joe Dicks, Ed Doherty, Jennifer A. Doerk, Thilo Du Bois, Andreas Duerst, Matthias Eccles, Diana Easton, Douglas T. Edwards, Robert P. Eilber, Ursula Ekici, Arif B. Fasching, Peter A. Fridley, Brooke L. Gao, Yu-Tang Gentry-Maharaj, Aleksandra Giles, Graham G. Glasspool, Rosalind Goode, Ellen L. Goodman, Marc T. Grownwald, Jacek Harrington, Patricia Harter, Philipp Hasmad, Hanis Nazihah Hein, Alexander Heitz, Florian Hildebrandt, Michelle A. T. Hillemanns, Peter Hogdall, Estrid Hogdall, Claus Hosono, Satoyo Iversen, Edwin S. Jakubowska, Anna James, Paul Jensen, Allan Ji, Bu-Tian Karlan, Beth Y. Kjaer, Susanne Kruger Kelemen, Linda E. Kellar, Melissa Kelley, Joseph L. Kiemeney, Lambertus A. Krakstad, Camilla Kupryjanczyk, Jolanta Lambrechts, Diether Lambrechts, Sandrina Le, Nhu D. Lee, Alice W. Lele, Shashi Leminen, Arto Lester, Jenny Levine, Douglas A. Liang, Dong Lissowska, Jolanta Lu, Karen Lubinski, Jan Lundvall, Lene Massuger, Leon F. A. G. Matsuo, Keitaro McGuire, Valerie McLaughlin, John R. Nevanlinna, Heli McNeish, Ian Menon, Usha Modugno, Francesmary Moysich, Kirsten B. Narod, Steven A. Nedergaard, Lotte Ness, Roberta B. Azmi, Mat Adenan Noor Odunsi, Kunle Olson, Sara H. Orlow, Irene Orsulic, Sandra Weber, Rachel Palmieri Pearce, Celeste L. Pejovic, Tanja Pelttari, Liisa M. Permuth-Wey, Jennifer Phelan, Catherine M. Pike, Malcolm C. Poole, Elizabeth M. Ramus, Susan J. Risch, Harvey A. Rosen, Barry Rossing, Mary Anne Rothstein, Joseph H. Rudolph, Anja Runnebaum, Ingo B. Rzepecka, Iwona K. Salvesen, Helga B. Schildkraut, Joellen M. Schwaab, Ira Sellers, Thomas A. Shu, Xiao-Ou Shvetsov, Yurii B. Siddiqui, Nadeem Sieh, Weiva Song, Honglin Southey, Melissa C. Sucheston, Lara Tangen, Ingvild L. Teo, Soo-Hwang Terry, Kathryn L. Thompson, Pamela J. Timorek, Agnieszka Tsai, Ya-Yu Tworoger, Shelley S. Van Altena, Anne M. Van Nieuwenhuysen, Els Vergote, Ignace Vierkant, Robert A. Wang-Gohrke, Shan Walsh, Christine Wentzensen, Nicolas Whittemore, Alice S. Wicklund, Kristine G. Wilkens, Lynne R. Woo, Yin-Ling Wu, Xifeng Wu, Anna H. Yang, Hannah Zheng, Wei Ziogas, Argyrios Monteiro, Alvaro Pharoah, Paul D. Gayther, Simon A. Freedman, Matthew L. Grp, Australian Ovarian Canc Study Bowtell, David Webb, Penelope M. Defazio, Anna CA Australian Ovarian Canc Study Grp TI Cis-eQTL analysis and functional validation of candidate susceptibility genes for high-grade serous ovarian cancer SO NATURE COMMUNICATIONS LA English DT Article ID GENOME-WIDE ASSOCIATION; LONG-RANGE INTERACTION; ANALYSES REVEAL; FALLOPIAN-TUBE; RISK LOCI; HOX GENES; IDENTIFICATION; EXPRESSION; BREAST; VARIANTS AB Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associated with HGSOC risk (P <= 10(-5)). For three cis-eQTL associations (P<1.4 x 10(-3), FDR<0.05) at 1p36 (CDC42), 1p34 (CDCA8) and 2q31 (HOXD9), we evaluate the functional role of each candidate by perturbing expression of each gene in HGSOC precursor cells. Overexpression of HOXD9 increases anchorage-independent growth, shortens population-doubling time and reduces contact inhibition. Chromosome conformation capture identifies an interaction between rs2857532 and the HOXD9 promoter, suggesting this SNP is a leading causal variant. Transcriptomic profiling after HOXD9 overexpression reveals enrichment of HGSOC risk variants within HOXD9 target genes (P = 6 x 10(-10) for risk variants (P<10(-4)) within 10 kb of a HOXD9 target gene in ovarian cells), suggesting a broader role for this network in genetic susceptibility to HGSOC. C1 [Lawrenson, Kate; Spindler, Tassja J.; Lee, Janet; Lee, Alice W.; Pearce, Celeste L.; Pike, Malcolm C.; Ramus, Susan J.; Wu, Anna H.; Gayther, Simon A.] Univ So Calif, Norris Comprehens Canc Ctr, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90033 USA. [Li, Qiyan] Xiamen Univ, Coll Med, Xiamen 361102, Peoples R China. [Seo, Ji-Heui; Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. [Kar, Siddhartha; Tyrer, Jonathan; Baker, Helen; Dicks, Ed; Song, Honglin; Pharoah, Paul D.] Univ Cambridge, Dept Publ Hlth & Primary Care, Dept Oncol, Strangeways Res Lab, Cambridge CB1 8RN, England. [Chen, Yibu] Univ So Calif, Bioinformat Serv, Norris Med Lib, Los Angeles, CA 90033 USA. [Karst, Alison; Drapkin, Ronny] Dana Farber Canc Inst, Dept Pathol, Boston, MA 02215 USA. [Karst, Alison; Drapkin, Ronny] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Aben, Katja K. H.] Radboud Univ Nijmegen, Med Ctr, Dept Hlth Evidence, NL-6500 HB Nijmegen, Netherlands. [Aben, Katja K. H.] Ctr Comprehens Canc, NL-3501 DB Utrecht, Netherlands. [Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Sch Med, Genet Epidemiol Res Inst, Dept Epidemiol, Irvine, CA 92697 USA. [Antonenkova, Natalia] Byelorussian Inst Oncol & Med Radiol Aleksandrov, Minsk 223040, Byelarus. [Bandera, Elisa V.] Rutgers Canc Inst New Jersey, Canc Prevent & Control, New Brunswick, NJ USA. [Bean, Yukie; Kellar, Melissa; Pejovic, Tanja] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97239 USA. [Beckmann, Matthias W.; Kellar, Melissa; Pejovic, Tanja] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA. [Fasching, Peter A.; Hein, Alexander] Univ Erlangen Nurnberg, Comprehens Canc Ctr Erlangen EMN, Univ Hosp Erlangen, Dept Gynecol & Obstet, D-91054 Erlangen, Germany. [Berchuck, Andrew] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. [Bisogna, Maria; Bjorge, Line; Levine, Douglas A.] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10065 USA. [Bogdanova, Natalia; Krakstad, Camilla; Salvesen, Helga B.; Tangen, Ingvild L.] Haukeland Hosp, Dept Gynecol & Obstet, N-5058 Bergen, Norway. [Bogdanova, Natalia; Krakstad, Camilla; Salvesen, Helga B.; Tangen, Ingvild L.] Univ Bergen, Dept Clin Sci, Ctr Canc Biomarkers, N-5020 Bergen, Norway. [Brinton, Louise A.; Doerk, Thilo] Hannover Med Sch, Gynaecol Res Unit, D-30625 Hannover, Germany. [Brooks-Wilson, Angela; Ji, Bu-Tian; Wentzensen, Nicolas; Yang, Hannah] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Bruinsma, Fiona] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada. [Bruinsma, Fiona] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada. [Butzow, Ralf; Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3004, Australia. [Campbell, Ian G.; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M.] Univ Helsinki, Cent Hosp, SF-00100 Helsinki, Finland. [Campbell, Ian G.] Univ Helsinki, Cent Hosp, Dept Pathol, FI-00014 Helsinki, Finland. [Carty, Karen] Peter MacCallum Canc Ctr, Canc Genet Lab, Div Res, Melbourne, Vic 3002, Australia. [Carty, Karen; Southey, Melissa C.] Univ Melbourne, Dept Pathol, Parkville, Vic 3010, Australia. [Carty, Karen] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic 3010, Australia. [Chang-Claude, Jenny; Glasspool, Rosalind; James, Paul] Beatson West Scotland Canc Ctr, Canc Res UK Clin Trials Unit, Glasgow G12 0YN, Lanark, Scotland. [Chenevix-Trench, Georgia; Eilber, Ursula; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany. [Chen, Anne] QIMR Berghofer Med Res Inst, Canc Div, Brisbane, Qld 4006, Australia. [Chen, Zhihua; Cook, Linda S.] H Lee Moffitt Canc Ctr & Res Inst, Dept Biostat, Tampa, FL 33612 USA. [Cramer, Daniel W.] Univ New Mexico, Div Epidemiol & Biostat, Dept Internal Med, Albuquerque, NM 87131 USA. [Cunningham, Julie M.; Terry, Kathryn L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Cunningham, Julie M.; Terry, Kathryn L.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02215 USA. [Cunningham, Julie M.; Terry, Kathryn L.] Harvard Univ, Sch Med, Boston, MA 02215 USA. Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Grownwald, Jacek; Jakubowska, Anna; Kupryjanczyk, Jolanta; Lubinski, Jan; Rzepecka, Iwona K.] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland. [Dennis, Joe; Easton, Douglas T.; Harrington, Patricia] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England. [Doherty, Jennifer A.] Geisel Sch Med Dartmouth, Dept Epidemiol, Lebanon, NH 03756 USA. [Du Bois, Andreas; Harter, Philipp; Heitz, Florian] Kliniken Essen Mitte, Dept Gynecol & Gynecol Oncol, D-45136 Essen, Germany. [Du Bois, Andreas; Harter, Philipp; Heitz, Florian] Dr Horst Schmidt Kliniken Wiesbaden, Dept Gynecol & Gynecol Oncol, D-65199 Wiesbaden, Germany. [Duerst, Matthias; Runnebaum, Ingo B.] Univ Jena, Jena Univ Hosp, Dept Gynecol, D-07737 Jena, Germany. [Eccles, Diana] Univ Southampton, Fac Med, Southampton SO16 5YA, Hants, England. [Edwards, Robert P.; Kelley, Joseph L.; Modugno, Francesmary] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA. [Edwards, Robert P.; Modugno, Francesmary] Univ Pittsburgh, Ovarian Canc Ctr Excellence, Pittsburgh, PA 15213 USA. [Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, Univ Hosp Erlangen, D-91054 Erlangen, Germany. [Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol & Oncol, Dept Med, Los Angeles, CA 90095 USA. [Fridley, Brooke L.] Univ Kansas, Med Ctr, Biostat & Informat Shared Resource, Kansas City, KS 66160 USA. [Gao, Yu-Tang] Shanghai Canc Inst, Shanghai 200030, Peoples R China. [Gentry-Maharaj, Aleksandra; Menon, Usha] UCL, Inst Womens Hlth, Dept Womens Canc, London W1T 7DN, England. [Giles, Graham G.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic 3010, Australia. [Goode, Ellen L.; Vierkant, Robert A.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Goodman, Marc T.; Thompson, Pamela J.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Canc Prevent & Control, Los Angeles, CA 90048 USA. [Goodman, Marc T.; Thompson, Pamela J.] Cedars Sinai Med Ctr, Dept Biomed Sci, Community & Populat Hlth Res Inst, Los Angeles, CA 90048 USA. [Hasmad, Hanis Nazihah; Teo, Soo-Hwang] Canc Res Initiat Fdn, Sime Darby Med Ctr, Subang Jaya 47500, Malaysia. [Hildebrandt, Michelle A. T.; Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Hillemanns, Peter] Hannover Med Sch, Dept Obstet, D-30625 Hannover, Germany. [Hillemanns, Peter] Hannover Med Sch, Dept Gynaecol, D-30625 Hannover, Germany. [Hogdall, Estrid] Danish Canc Soc, Inst Canc Epidemiol, DK-2100 Copenhagen, Denmark. [Hogdall, Estrid; Lundvall, Lene] Univ Copenhagen, Herlev Hosp, Dept Pathol, Mol Unit, DK-1165 Copenhagen, Denmark. [Hogdall, Claus] Univ Copenhagen, Gyn Clin, Rigshosp, Copenhagen, Denmark. [Hosono, Satoyo] Aichi Canc Ctr Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi 4640021, Japan. [Iversen, Edwin S.] Duke Univ, Dept Stat Sci, Durham, NC 27708 USA. [Jensen, Allan] Univ Copenhagen, Dept Gynecol, Rigshosp, DK-2100 Copenhagen, Denmark. [Karlan, Beth Y.; Lester, Jenny; Orsulic, Sandra; Walsh, Christine] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA. [Kjaer, Susanne Kruger] Danish Canc Soc Res Ctr, Dept Virus Lifestyle & Genes, DK-2100 Copenhagen, Denmark. [Kjaer, Susanne Kruger] Univ Copenhagen, Dept Gynaecol, Juliane Marie Ctr, Rigshosp, DK-2100 Copenhagen, Denmark. [Kelemen, Linda E.] Med Univ S Carolina, Dept Publ Hlth Sci, Coll Med, Charleston, SC 29435 USA. [Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Mentre, Radboud Inst Hlth Sci, NL-6500 HB Nijmegen, Netherlands. [Lambrechts, Diether] VIB, Vesalius Res Ctr, B-3000 Leuven, Belgium. [Lambrechts, Diether] Univ Leuven, Dept Oncol, Lab Translat Genet, B-3000 Leuven, Belgium. [Lambrechts, Sandrina; Van Nieuwenhuysen, Els; Vergote, Ignace] Univ Hosp Leuven, Div Gynecol Oncol, Dept Oncol, B-3000 Leuven, Belgium. [Le, Nhu D.] BC Canc Agcy, Canc Control Res, Vancouver, BC V5Z 1L3, Canada. [Lele, Shashi; Moysich, Kirsten B.; Sucheston, Lara] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [Liang, Dong] Texas So Univ, Coll Pharm & Hlth Sci, Houston, TX 77004 USA. [Lissowska, Jolanta] Maria Sklodowska Curie Mem Canc Ctr & Inst Oncol, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Lu, Karen] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. [Massuger, Leon F. A. G.; Van Altena, Anne M.] Radboud Univ Nijmegen Med Ctr, Dept Gynaecol, NL-6500 HB Nijmegen, Netherlands. [Matsuo, Keitaro] Kyushu Univ, Fac Med Sci, Dept Prevent Med, Fukuoka 8190395, Japan. [McGuire, Valerie; Rothstein, Joseph H.; Sieh, Weiva; Whittemore, Alice S.] Stanford Univ, Sch Med, Dept Hlth Res & Policy Epidemiol, Stanford, CA 94305 USA. [McLaughlin, John R.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada. [McNeish, Ian] Univ Glasgow, Inst Canc Sci, Wolfson Wohl Canc Res Ctr, Beatson Inst Canc Res, Glasgow G61 1QH, Lanark, Scotland. [Modugno, Francesmary] Magee Womens Res Inst, Womens Canc Res Program, Pittsburgh, PA 15213 USA. [Modugno, Francesmary] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA. [Modugno, Francesmary] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Narod, Steven A.; Olson, Sara H.; Orlow, Irene] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA. [Nedergaard, Lotte] Univ Copenhagen, Dept Pathol, Rigshosp, DK-2100 Copenhagen, Denmark. [Ness, Roberta B.] Univ Texas Sch Publ Hlth, Houston, TX 77030 USA. [Azmi, Mat Adenan Noor; Woo, Yin-Ling] Univ Malaya, Univ Malaya Med Ctr, Dept Obstet & Gynaecol, Kuala Lumpur 50603, Malaysia. [Odunsi, Kunle] Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA. [Weber, Rachel Palmieri] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. [Permuth-Wey, Jennifer; Phelan, Catherine M.; Sellers, Thomas A.; Tsai, Ya-Yu] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL 33612 USA. [Pike, Malcolm C.; Poole, Elizabeth M.; Tworoger, Shelley S.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02215 USA. [Pike, Malcolm C.; Poole, Elizabeth M.; Tworoger, Shelley S.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Poole, Elizabeth M.; Tworoger, Shelley S.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Risch, Harvey A.] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT 06510 USA. [Rosen, Barry] Univ Toronto, Fac Med, Dept Gynecol Oncol, Princess Margaret Hosp, Toronto, ON M5S 2J7, Canada. [Rosen, Barry] Univ Toronto, Fac Med, Dept Obstet & Gynecol, Toronto, ON M5S 2J7, Canada. [Rossing, Mary Anne; Wicklund, Kristine G.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Rossing, Mary Anne] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Schildkraut, Joellen M.] Duke Canc Inst, Canc Control & Populat Sci, Durham, NC 27710 USA. [Schildkraut, Joellen M.; Schwaab, Ira] Inst Humangenet Wiesbaden, D-65187 Wiesbaden, Germany. [Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Sch Med, Div Epidemiol,Dept Med, Nashville, TN 37232 USA. [Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA. [Shvetsov, Yurii B.; Wilkens, Lynne R.] Univ Hawaii, Canc Epidemiol Program, Ctr Canc, Honolulu, HI 96813 USA. [Siddiqui, Nadeem] Glasgow Royal Infirm, Dept Gynaecol Oncol, Glasgow G4 0SF, Lanark, Scotland. [Teo, Soo-Hwang; Woo, Yin-Ling] Univ Malaya, Canc Res Inst, Fac Med, Med Ctr, Kuala Lumpur 50603, Malaysia. [Timorek, Agnieszka] Med Univ Warsaw, Fac Med 2, Dept Obstet Gynecol & Oncol, Warsaw, Poland. [Timorek, Agnieszka] Brodnowski Hosp, Warsaw, Poland. [Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynecol, D-89075 Ulm, Germany. [Monteiro, Alvaro] H Lee Moffitt Canc Ctr & Res Inst, Div Populat Sci, Canc Epidemiol Program, Tampa, FL 33612 USA. [Bowtell, David] Peter MacCallum Canc Ctr, Melbourne, Vic 3002, Australia. [Webb, Penelope M.] QIMR Berghofer, Brisbane, Qld 4006, Australia. [Defazio, Anna] Univ Sydney, Westmead Millennium Inst, Westmead Hosp, Westmead, NSW 2145, Australia. [Defazio, Anna] Univ Sydney, Westmead Millennium Inst, Ctr Canc Res, Westmead, NSW 2145, Australia. RP Gayther, SA (reprint author), Univ So Calif, Norris Comprehens Canc Ctr, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90033 USA. EM simon.gayther@med.usc.edu RI Bowtell, David/H-1007-2016; Dork, Thilo/J-8620-2012; Massuger, Leon/H-8072-2014; Hein, Alexander/F-6999-2010; Bjorge, Line/C-1307-2017; salvesen, Helga/C-1187-2017; Brooks-Wilson, Angela/E-9399-2012; van Altena, Anne/B-9824-2016; U-ID, Kyushu/C-5291-2016; Drapkin, Ronny/E-9944-2016; Teo, Soo-hwang/H-2353-2014; Aben, Katja/G-9686-2016 OI Ramus, Susan/0000-0003-0005-7798; Orlow, Irene/0000-0001-6234-6961; Krakstad, Camilla/0000-0002-0174-8139; Giles, Graham/0000-0003-4946-9099; Matsuo, Keitaro/0000-0003-1761-6314; Bowtell, David/0000-0001-9089-7525; Hein, Alexander/0000-0003-2601-3398; Bjorge, Line/0000-0002-0240-2770; salvesen, Helga/0000-0002-4438-8831; Glasspool, Rosalind/0000-0002-5000-1680; Brooks-Wilson, Angela/0000-0003-1009-6408; Drapkin, Ronny/0000-0002-6912-6977; Aben, Katja/0000-0002-0214-2147 FU European Commission [223175-HEALTH-F2-2009-223175]; Ovarian Cancer Research Fund [PPD/RPCI.07]; US National Cancer Institute (NCI) GAME-ON Post-GWAS Initiative [U19-CA148112]; Wellcome Trust [076113] FX Grant Support-higher level funding: the COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175-HEALTH-F2-2009-223175). The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific development and funding for this project were in part supported by the US National Cancer Institute (NCI) GAME-ON Post-GWAS Initiative (U19-CA148112). This study made use of data generated by the Wellcome Trust Case Control consortium. Funding for the project was provided by the Wellcome Trust under award 076113. The results published here are in part based on data generated by The Cancer Genome Atlas Project established by the NCI and National Human Genome Research Institute. NR 62 TC 4 Z9 4 U1 3 U2 12 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 SEP PY 2015 VL 6 AR 8234 DI 10.1038/ncomms9234 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT7TN UT WOS:000363017500005 PM 26391404 ER PT J AU Tajima, K Yae, T Javaid, S Tam, O Comaills, V Morris, R Wittner, BS Liu, MZ Engstrom, A Takahashi, F Black, JC Ramaswamy, S Shioda, T Hammell, M Haber, DA Whetstine, JR Maheswaran, S AF Tajima, Ken Yae, Toshifumi Javaid, Sarah Tam, Oliver Comaills, Valentine Morris, Robert Wittner, Ben S. Liu, Mingzhu Engstrom, Amanda Takahashi, Fumiyuki Black, Joshua C. Ramaswamy, Sridhar Shioda, Toshihiro Hammell, Molly Haber, Daniel A. Whetstine, Johnathan R. Maheswaran, Shyamala TI SETD1A modulates cell cycle progression through a miRNA network that regulates p53 target genes SO NATURE COMMUNICATIONS LA English DT Article ID PROSTATE-CANCER; CLIP-SEQ; EXPRESSION; MICRORNAS; LUNG; TUMORIGENESIS; METHYLATION; STARBASE; BTG2; SITE AB Expression of the p53-inducible antiproliferative gene BTG2 is suppressed in many cancers in the absence of inactivating gene mutations, suggesting alternative mechanisms of silencing. Using a shRNA screen targeting 43 histone lysine methyltransferases (KMTs), we show that SETD1A suppresses BTG2 expression through its induction of several BTG2-targeting miRNAs. This indirect but highly specific mechanism, by which a chromatin regulator that mediates transcriptional activating marks can lead to the downregulation of a critical effector gene, is shared with multiple genes in the p53 pathway. Through such miRNA-dependent effects, SETD1A regulates cell cycle progression in vitro and modulates tumorigenesis in mouse xenograft models. Together, these observations help explain the remarkably specific genetic consequences associated with alterations in generic chromatin modulators in cancer. C1 [Tajima, Ken; Yae, Toshifumi; Javaid, Sarah; Comaills, Valentine; Morris, Robert; Wittner, Ben S.; Liu, Mingzhu; Engstrom, Amanda; Takahashi, Fumiyuki; Black, Joshua C.; Ramaswamy, Sridhar; Shioda, Toshihiro; Haber, Daniel A.; Whetstine, Johnathan R.; Maheswaran, Shyamala] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Tam, Oliver; Hammell, Molly] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Maheswaran, Shyamala] Harvard Univ, Sch Med, Dept Surg, Charlestown, MA 02129 USA. RP Whetstine, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM johnathan_whetstine@hms.harvard.edu; Maheswaran@helix.mgh.harvard.edu RI Black, Joshua/Q-2484-2015; OI Wittner, Ben/0000-0001-5657-9849 FU Susan G. Komen for the Cure Grant [KG09042]; NCI Federal Share Program; Lilly Oncology Fellowship from The Japanese Respiratory Society; Kanzawa Medical Research Foundation; Mochida Memorial Foundation for Medical and Pharmaceutical Research; ACS [RSG-13-115-01-CCG]; NIH [R01GM097360]; Jane Coffin Childs Memorial Fund for Medical Research; MGH ECOR Tosteson FX We thank Drs Motamedi and Dyson for helpful discussions and critical reading of this manuscript. This work was supported by Susan G. Komen for the Cure Grant KG09042 and the NCI Federal Share Program and Income to MGH Martin Research Prize (to S.M.); The Lilly Oncology Fellowship from The Japanese Respiratory Society, Overseas Study Grant from Kanzawa Medical Research Foundation and Mochida Memorial Foundation for Medical and Pharmaceutical Research (to T.Y.); and ACS (RSG-13-115-01-CCG to J.R.W.) and NIH (R01GM097360 to J.R.W.); J.W. is a Leukemia and Lymphoma Scholar and Tepper Family MGH Research Scholar. The Jane Coffin Childs Memorial Fund for Medical Research (to J.B.) and MGH ECOR Tosteson postdoctoral fellowship (to J.B.). NR 29 TC 2 Z9 2 U1 2 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD SEP PY 2015 VL 6 AR 8257 DI 10.1038/ncomms9257 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT7TN UT WOS:000363017500028 PM 26394836 ER PT J AU Shahunja, KM Leung, DT Ahmed, T Bardhan, PK Ahmed, D Qadri, F Ryan, ET Chisti, MJ AF Shahunja, K. M. Leung, Daniel T. Ahmed, Tahmeed Bardhan, Pradip Kumar Ahmed, Dilruba Qadri, Firdausi Ryan, Edward T. Chisti, Mohammod Jobayer TI Factors Associated with Non-typhoidal Salmonella Bacteremia versus Typhoidal Salmonella Bacteremia in Patients Presenting for Care in an Urban Diarrheal Disease Hospital in Bangladesh SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID BLOOD-STREAM INFECTIONS; CHILDREN; RESISTANCE; DHAKA; GASTROENTERITIS; MORTALITY; COUNTRIES; THAILAND; ADULTS; FEVER AB Background Non-typhoidal Salmonella (NTS) and Salmonella enterica serovar Typhi bacteremia are the causes of significant morbidity and mortality worldwide. There is a paucity of data regarding NTS bacteremia in South Asia, a region with a high incidence of typhoidal bacteremia. We sought to determine clinical predictors and outcomes associated with NTS bacteremia compared with typhoidal bacteremia. Methodology We performed a retrospective age-matched case-control study of patients admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh, between February 2009 and March 2013. We compared demographic, clinical, microbiological, and outcome variables of NTS bacteremic patients with age-matched S. Typhi bacteremic patients, and a separate comparison of patients with NTS bacteremia and patients with NTS gastroenteritis. Principal Findings Of 20 patients with NTS bacteremia, 5 died (25% case fatality), compared to none of 60 age-matched cases of S. Typhi bacteremia. In univariate analysis, we found that compared with S. Typhi bacteremia, cases of NTS bacteremia had more severe acute malnutrition (SAM) in children under five years of age, less often presented with a duration of fever >= 5 days, and were more likely to have co-morbidities on admission such as pneumonia and clinical signs of sepsis (p< 0.05 in all cases). In multivariable logistic regression, SAM, clinical sepsis, and pneumonia were independent risk factors for NTS bacteremia compared with S. Typhi bacteremia (p< 0.05 in all cases). Notably, we found marked differences in antibiotic susceptibilities, including NTS strains resistant to antibiotics commonly used for empiric therapy of patients suspected to have typhoid fever. Conclusions/Significance Diarrheal patients with NTS bacteremia more often presented with co-morbidities and had a higher case fatality rate compared to those with typhoidal bacteremia. Clinicians in regions where both typhoid and NTS bacteremia are prevalent need to be vigilant about the possibility of both entities, especially given notable differences in antibiotic susceptibility patterns. C1 [Shahunja, K. M.; Ahmed, Tahmeed; Chisti, Mohammod Jobayer] ICDDR B, CNFS, Dhaka, Bangladesh. [Leung, Daniel T.; Ahmed, Dilruba; Qadri, Firdausi] ICDDR B, Ctr Vaccine Sci, Dhaka, Bangladesh. [Leung, Daniel T.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Leung, Daniel T.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Bardhan, Pradip Kumar; Chisti, Mohammod Jobayer] ICDDR B, Dhaka Hosp, Dhaka, Bangladesh. RP Shahunja, KM (reprint author), ICDDR B, CNFS, Dhaka, Bangladesh. EM chisti@icddrb.org OI leung, daniel/0000-0001-8401-0801 FU American Society of Tropical Medicine and Hygiene/Burroughs Wellcome Fund; [AI100023]; [AI100923] FX This research was supported by core grants to the icddr,b and additionally supported by the following grants: AI100923 (to DTL), AI100023 (to ETR), and a Postdoctoral Fellowship in Tropical Infectious Diseases from the American Society of Tropical Medicine and Hygiene/Burroughs Wellcome Fund (to DTL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 2 Z9 2 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD SEP PY 2015 VL 9 IS 9 AR e0004066 DI 10.1371/journal.pntd.0004066 PG 12 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA CT7YI UT WOS:000363031200046 PM 26361076 ER PT J AU Karavan, M Olerud, J Bouldin, E Taylor, L Reiber, GE AF Karavan, Mahsa Olerud, John Bouldin, Erin Taylor, Leslie Reiber, Gayle E. TI Evidence-based chronic ulcer care and lower limb outcomes among Pacific Northwest veterans SO WOUND REPAIR AND REGENERATION LA English DT Article DE evidence-based care; ulcer; lower limb; veterans ID DIABETIC FOOT ULCERS; PERIPHERAL ARTERIAL-DISEASE; VENOUS ULCERS; WOUND CARE; GUIDELINES; DEBRIDEMENT AB Evidence-based ulcer care guidelines detail optimal components of care for treatment of ulcers of different etiologies. We investigated the impact of providing specific evidence-based ulcer treatment components on healing outcomes for lower limb ulcers (LLU) among veterans in the Pacific Northwest. Components of evidence-based ulcer care for venous, arterial, diabetic foot ulcers/neuropathic ulcers were abstracted from medical records. The outcome was ulcer healing. Our analysis assessed the relationship between evidence-based ulcer care by etiology, components of care provided, and healing, while accounting for veteran characteristics. A minority of veterans in all three ulcer-etiology groups received the recommended components of evidence-based care in at least 80% of visits. The likelihood of healing improved when assessment for edema and infection were performed on at least 80% of visits (hazard ratio [HR]=3.20, p=0.009 and HR=3.54, p=0.006, respectively) in patients with venous ulcers. There was no significant association between frequency of care components provided and healing among patients with arterial ulcers. Among patients with diabetic/neuropathic ulcers, the chance of healing increased 2.5-fold when debridement was performed at 80% of visits (p=0.03), and doubled when ischemia was assessed at the first visit (p=0.045). Veterans in the Pacific Northwest did not uniformly receive evidence-based ulcer care. Not all evidence-based ulcer care components were significantly associated with healing. At a minimum, clinicians need to address components of ulcer care associated with improved ulcer healing. C1 [Karavan, Mahsa; Bouldin, Erin; Taylor, Leslie; Reiber, Gayle E.] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Hlth Serv Res & Dev, Seattle, WA 98101 USA. [Karavan, Mahsa; Olerud, John] Univ Washington, Sch Med, Seattle, WA USA. [Olerud, John] Univ Washington, Div Dermatol, Seattle, WA 98195 USA. [Bouldin, Erin; Reiber, Gayle E.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Bouldin, Erin; Reiber, Gayle E.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Reiber, GE (reprint author), VA Puget Sound Hlth Care Syst, 152,Met Pk West 1400,1100 Olive Way, Seattle, WA 98101 USA. EM gayle.reiber@va.gov OI Bouldin, Erin/0000-0001-7550-309X NR 38 TC 3 Z9 3 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1067-1927 EI 1524-475X J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD SEP-OCT PY 2015 VL 23 IS 5 BP 745 EP 752 DI 10.1111/wrr.12341 PG 8 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA CU2YW UT WOS:000363390900013 PM 26171654 ER PT J AU Zafar, SY Chino, F Ubel, PA Rushing, C Samsa, G Altomare, I Nicolla, J Schrag, D Tulsky, JA Abernethy, AP Peppercorn, JM AF Zafar, S. Yousuf Chino, Fumiko Ubel, Peter A. Rushing, Christel Samsa, Gregory Altomare, Ivy Nicolla, Jonathan Schrag, Deborah Tulsky, James A. Abernethy, Amy P. Peppercorn, Jeffery M. TI The Utility of Cost Discussions Between Patients With Cancer and Oncologists SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID OF-POCKET COSTS; PHYSICIAN COMMUNICATION; RACIAL-DIFFERENCES; ECONOMIC BURDEN; UNITED-STATES; CARE; CHEMOTHERAPY; PROJECTIONS; THERAPY; ADULTS AB Objectives: Patients with cancer can experience substantial financial burden. Little is known about patients' preferences for incorporating cost discussions into treatment decision making or about the ramifications of those discussions. The objective of this study was to determine patient preferences for and benefits of discussing costs with doctors. Study Design: Cross-sectional, survey study. Methods: We enrolled insured adults with solid tumors on anticancer therapy who were treated at a referral cancer center or an affiliated rural cancer clinic. Patients were surveyed at enrollment and again 3 months later about cost discussions with doctors, decision making, and financial burden. Medical records were abstracted for disease and treatment data. Logistic regression investigated characteristics associated with greater desire to discuss costs. Results: Of 300 patients (86% response rate), 52% expressed some desire to discuss treatment-related out-of-pocket costs with doctors and 51% wanted their doctor to take costs into account to some degree when making treatment decisions. However, only 19% had talked to their doctor about costs. Of those, 57% reported lower out-of-pocket costs as a result of cost discussions. In multivariable logistic regression, higher subjective financial distress was associated with greater likelihood to desire cost discussions (odds ratio [OR], 1.22; 95% CI, 1.10-1.36). Nonwhite race was associated with lower likelihood to desire cost discussions (OR, 0.53; 95% CI, 0.30-0.95). Conclusions: Patients with cancer varied in their desire to discuss costs with doctors, but most who discussed costs believed the conversations helped reduce their expenses. Patient-physician cost communication might reduce out-of-pocket costs even in oncology where treatment options are limited. C1 [Zafar, S. Yousuf; Altomare, Ivy; Abernethy, Amy P.] Duke Canc Inst, Durham, NC 27705 USA. [Chino, Fumiko; Rushing, Christel; Samsa, Gregory; Nicolla, Jonathan] Duke Univ, Med Ctr, Durham, NC USA. [Ubel, Peter A.] Duke Univ, Fuqua Sch Business, Durham, NC 27706 USA. [Schrag, Deborah; Tulsky, James A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Peppercorn, Jeffery M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Zafar, SY (reprint author), Duke Canc Inst, DUMC 3505, Durham, NC 27705 USA. EM yousuf.zafar@duke.edu FU Duke Cancer Institute Cancer Control Pilot Studies Program; Duke Clinical Research Institute Comparative Effectiveness KM1 Award [1KM-1CA156687-01]; American Cancer Society Mentored Research Scholar Grant [121276-MRSG-11-171-01-PCSM] FX This work was supported by a Duke Cancer Institute Cancer Control Pilot Studies Program and the Duke Clinical Research Institute Comparative Effectiveness KM1 Award (1KM-1CA156687-01). Dr Zafar is supported by an American Cancer Society Mentored Research Scholar Grant (121276-MRSG-11-171-01-PCSM). NR 33 TC 4 Z9 4 U1 1 U2 4 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD SEP PY 2015 VL 21 IS 9 BP 607 EP + PG 10 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CT6UI UT WOS:000362947500006 PM 26618364 ER PT J AU Ouyang, CM Dwyer, JT Jacques, PF Chuang, LM Haas, CF Weinger, K AF Ouyang, Chung-Mei Dwyer, Johanna T. Jacques, Paul F. Chuang, Lee-Ming Haas, Catherine F. Weinger, Katie TI Determinants of dietary self-care behaviours among Taiwanese patients with type 2 diabetes SO ASIA PACIFIC JOURNAL OF CLINICAL NUTRITION LA English DT Article DE type 2 diabetes mellitus; Taiwan; self-care behaviours; patient education; dietary adherence ID MANAGEMENT AB The effects of patient characteristics on reported adherence to dietary self-care behaviours in 184 Taiwanese outpatients 40 years or older with type 2 diabetes was assessed. Patient characteristics included the presence of predisposing factors affecting diabetes adherence (knowledge and attitudes about the disease, self-efficacy, and the absence of psychological problems), enabling factors (understanding of diabetes and environmental factors affecting it), and reinforcing factors (presence of medical and social support) which were evaluated using a 72 item self-administered questionnaire with 8 subscales. Adherence was assessed by patients' reports of carrying out 7 self-care behaviours (following a diabetic meal plan, following the diabetes exchange system, eating meals providing the same amount of carbohydrate every day, counting carbohydrates, reducing dietary fat, consuming high fiber foods, and keeping a daily food record). Reported adherence ranged from 17% to 74%. No single predisposing, enabling, or reinforcing factor predicted adherence to all of the dietary self-care behaviours. However, more self-efficacy, better understanding, and a better attitude toward diabetes were associated with performing five or more of the dietary self-care behaviours examined. With respect to specific self-care behaviours, women were more likely than men to count carbohydrates (OR=5.75) and reduce fat in their diets (OR=2.57). Patients who attended more nutrition education sessions were more likely to follow diabetes meal plans (OR=2.11) and the diabetes exchange system (OR=3.07). Efforts are needed to encourage providers to teach diabetes self-care behaviours to patients and to capitalize upon demographic and psychosocial characteristics that can enhance patient adherence. C1 [Ouyang, Chung-Mei] Natl Taiwan Univ Hosp, Dept Dietet, Taipei, Taiwan. [Ouyang, Chung-Mei; Dwyer, Johanna T.; Jacques, Paul F.; Haas, Catherine F.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [Chuang, Lee-Ming] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan. [Weinger, Katie] Harvard Univ, Sch Med, Sect Behav & Mental Hlth Res, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Dwyer, JT (reprint author), Tufts Med Ctr, Frances Stern Nutr Ctr, 800 Washington St,Box 783, Boston, MA 02111 USA. EM dwyerj1@od.nih.gov OI Dwyer, Johanna/0000-0002-0783-1769 FU National Taiwan University Hospital, Taipei, Taiwan; Fund for Research and Teaching, Frances Stern Nutrition Center at Tufts Medical Center, Boston MA; U.S. Department of Agriculture, Agricultural Research Service [58-1950-0-014] FX This study was supported with grants and resources from the National Taiwan University Hospital, Taipei, Taiwan. Support was received from the Fund for Research and Teaching, Frances Stern Nutrition Center at Tufts Medical Center, Boston MA and by the U.S. Department of Agriculture, Agricultural Research Service, under agreement No. 58-1950-0-014. NR 17 TC 2 Z9 3 U1 3 U2 13 PU H E C PRESS, HEALTHY EATING CLUB PTY LTD PI MCKINNON PA PO BOX 4121, MCKINNON, VIC 3204, AUSTRALIA SN 0964-7058 J9 ASIA PAC J CLIN NUTR JI Asia Pac. J. Clin. Nutr. PD SEP PY 2015 VL 24 IS 3 BP 430 EP 437 DI 10.6133/apjcn.2015.24.3.02 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CT6JP UT WOS:000362919600009 PM 26420183 ER PT J AU Ouyang, CM Dwyer, JT Jacques, PF Chuang, LM Haas, CF Weinger, K AF Ouyang, Chung-Mei Dwyer, Johanna T. Jacques, Paul F. Chuang, Lee-Ming Haas, Catherine F. Weinger, Katie TI Diabetes self-care behaviours and clinical outcomes among Taiwanese patients with type 2 diabetes SO ASIA PACIFIC JOURNAL OF CLINICAL NUTRITION LA English DT Article DE type 2 diabetes mellitus; Taiwan; self-care behaviours; patient education; clinical outcomes ID MANAGEMENT; INTERVENTION; INDIVIDUALS; PREVALENCE; KNOWLEDGE; DISEASE; ADULTS; DIET; LIFE AB We examined the influences of patients' background characteristics on the frequency of performing five diabetes self-care behaviours that 185 Taiwanese outpatients reported. All patients had type 2 diabetes diagnosed for more than a year and attended an outpatient clinic at a large university hospital where they had received at least one dietitian-led individual nutrition education session and one nurse-led diabetes education session during the course of their care. Seventy nine percent of the patients regularly (defined as responses often or always on the questionnaire) took their medications and over half followed recommended meal plans and exercised, but fewer performed foot care (38%) or checked their blood glucose levels (20%) regularly. The associations between patients' demographics and disease-related characteristics and their performance of self-care behaviours were assessed with logistic regression. Although checking blood glucose levels and performing diabetes foot care were unrelated to any clinical outcome examined, patients who took their diabetes medications had lower hemoglobin AI levels and fewer chronic complications than those who did not. Furthermore, patients who followed a diabetes meal plan also had lower hemoglobin A(1c) levels, and those who exercised regularly had healthier body mass indices (BMI) than those who did not C1 [Ouyang, Chung-Mei] Natl Taiwan Univ Hosp, Dept Dietet, Taipei, Taiwan. [Ouyang, Chung-Mei; Dwyer, Johanna T.; Jacques, Paul F.; Haas, Catherine F.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [Chuang, Lee-Ming] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan. [Weinger, Katie] Harvard Univ, Sch Med, Sect Behav & Mental Hlth Res, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Dwyer, JT (reprint author), Tufts Med Ctr, Frances Stern Nutr Ctr, 800 Washington St,Box 783, Boston, MA 02111 USA. EM dwyerj1@od.nih.gov OI Dwyer, Johanna/0000-0002-0783-1769 FU National Taiwan University Hospital, Taipei, Taiwan; Fund for Research and Teaching, Frances Stern Nutrition Center at Tufts Medical Center, Boston MA; U.S. Department of Agriculture, Agricultural Research Service [58-1950-0-014] FX This study was supported with grants and resources from the National Taiwan University Hospital, Taipei, Taiwan. Support was received from the Fund for Research and Teaching, Frances Stern Nutrition Center at Tufts Medical Center, Boston MA and by the U.S. Department of Agriculture, Agricultural Research Service, under agreement No. 58-1950-0-014. NR 27 TC 1 Z9 1 U1 1 U2 1 PU H E C PRESS, HEALTHY EATING CLUB PTY LTD PI MCKINNON PA PO BOX 4121, MCKINNON, VIC 3204, AUSTRALIA SN 0964-7058 J9 ASIA PAC J CLIN NUTR JI Asia Pac. J. Clin. Nutr. PD SEP PY 2015 VL 24 IS 3 BP 438 EP 443 DI 10.6133/apjcn.2015.24.3.03 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CT6JP UT WOS:000362919600010 PM 26420184 ER PT J AU Wang, MY Han, LJ Liu, SS Zhao, XB Yang, JH Loh, SK Sun, XM Zhang, CX Fang, X AF Wang, Mingyu Han, Lijuan Liu, Shasha Zhao, Xuebing Yang, Jinghua Loh, Soh Kheang Sun, Xiaomin Zhang, Chenxi Fang, Xu TI A Weibull statistics-based lignocellulose saccharification model and a built-in parameter accurately predict lignocellulose hydrolysis performance SO BIOTECHNOLOGY JOURNAL LA English DT Article DE Cellulase; Delignined corncob residue; Empty fruit bunch; Lignocelluloses saccharification model; Weibull statistics ID ENZYMATIC-HYDROLYSIS; BIOETHANOL PRODUCTION; SUGARCANE BAGASSE; PRODUCT INHIBITION; CELLULOSIC BIOMASS; ETHANOL-PRODUCTION; KINETIC-MODEL; FED-BATCH; PRETREATMENT; ACID AB Renewable energy from lignocellulosic biomass has been deemed an alternative to depleting fossil fuels. In order to improve this technology, we aim to develop robust mathematical models for the enzymatic lignocellulose degradation process. By analyzing 96 groups of previously published and newly obtained lignocellulose saccharification results and fitting them to Weibull distribution, we discovered Weibull statistics can accurately predict lignocellulose saccharification data, regardless of the type of substrates, enzymes and saccharification conditions. A mathematical model for enzymatic lignocellulose degradation was subsequently constructed based on Weibull statistics. Further analysis of the mathematical structure of the model and experimental saccharification data showed the significance of the two parameters in this model. In particular, the. value, defined the characteristic time, represents the overall performance of the saccharification system. This suggestion was further supported by statistical analysis of experimental saccharification data and analysis of the glucose production levels when lambda and n values change. In conclusion, the constructed Weibull statistics-based model can accurately predict lignocellulose hydrolysis behavior and we can use the lambda parameter to assess the overall performance of enzymatic lignocellulose degradation. Advantages and potential applications of the model and the lambda value in saccharification performance assessment were discussed. C1 [Wang, Mingyu; Han, Lijuan; Liu, Shasha; Fang, Xu] Shandong Univ, Sch Life Sci, State Key Lab Microbial Technol, Jinan 250100, Peoples R China. [Zhao, Xuebing] Tsinghua Univ, Dept Chem Engn, Inst Appl Chem, Beijing 100084, Peoples R China. [Yang, Jinghua] Boston Univ, VA Boston Healthcare Syst, Dept Surg, Boston, MA 02215 USA. [Yang, Jinghua] Shandong Univ, Sch Med, Canc Res Ctr, Jinan 250100, Peoples R China. [Loh, Soh Kheang] Malaysian Palm Oil Board, Kuala Lumpur, Malaysia. [Sun, Xiaomin] Shandong Univ, Environm Res Inst, Jinan 250100, Peoples R China. [Zhang, Chenxi] Binzhou Univ, Dept Resource & Environm, Binzhou, Peoples R China. RP Fang, X (reprint author), Shandong Univ, Sch Life Sci, State Key Lab Microbial Technol, Jinan 250100, Peoples R China. EM fangxu@sdu.edu.cn RI sdu, eri/O-2991-2015; SDU, Environ Res/P-4462-2015; Fang, Xu/B-8313-2015; Zhao, Xuebing/E-6301-2011 OI Fang, Xu/0000-0002-9196-5697; Zhao, Xuebing/0000-0002-4094-268X FU National Key Technology R&D Program of China [2014BAD02B07]; National Energy Applied Technology Research and Demonstration Project [NY20130402]; National Natural Science Foundation of China [31200051]; Shandong Province Natural Science Foundation [ZR2012CQ022, ZR2013CM041]; Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry; Malaysian Palm Oil Board Special Board-Approved Projects [R008709000] FX This work was supported by the National Key Technology R&D Program of China (No. 2014BAD02B07), National Energy Applied Technology Research and Demonstration Project (No. NY20130402), National Natural Science Foundation of China (No. 31200051), Shandong Province Natural Science Foundation (No. ZR2012CQ022 and ZR2013CM041), Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry and the Malaysian Palm Oil Board Special Board-Approved Projects (No. R008709000). NR 30 TC 2 Z9 2 U1 2 U2 12 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 101161, 69451 WEINHEIM, GERMANY SN 1860-6768 EI 1860-7314 J9 BIOTECHNOL J JI Biotechnol. J. PD SEP PY 2015 VL 10 IS 9 BP 1424 EP 1433 DI 10.1002/biot.201400723 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA CT3RK UT WOS:000362724300008 PM 26121186 ER PT J AU Lin, EY Cohen, HW Bhatt, AB Stefanescu, A Dudzinski, D Yeh, DD Johnson, J Lui, GK AF Lin, Elaine Y. Cohen, Hillel W. Bhatt, Ami B. Stefanescu, Ada Dudzinski, David Yeh, Doreen DeFaria Johnson, Jacob Lui, George K. TI Predicting Outcomes Using the Heart Failure Survival Score in Adults with Moderate or Complex Congenital Heart Disease SO CONGENITAL HEART DISEASE LA English DT Article DE Prognosis; ACHD; Mortality; Morbidity; Risk; Model ID HIGH-RISK; MORTALITY; EXERCISE; ARRHYTHMIAS; PREVALENCE; SUDDEN; DEATH; MODEL; TERM AB BackgroundAdults with congenital heart disease (CHD) face increased risk for morbidity and mortality with age, but few prognostic models exist. ObjectiveThis study aims to assess whether the Heart Failure Survival Score (HFSS), which risk stratifies patients for heart transplantation, predicts outcomes in adults with moderate or complex CHD. MethodsThis was a multicenter, retrospective study which identified 441 patients with moderate or complex CHD between 2005 and 2013, of whom 169 had all the HFSS parameters required to calculate the risk score. Because all study patients were deemed low risk by the HFSS, the score was dichotomized at the median (10.4). Outcomes included death, transplant or ventricular assist device (VAD), arrhythmia requiring treatment, nonelective cardiovascular (CV) hospitalizations, and the composite. Associations of mean HFSS and HFSS <10.4 with each outcome were assessed. ResultsThe cohort had mean standard deviation age of 33.6 +/- 12.6 years, peak VO2 21.8 +/- 7.5mL/kg/min, HFSS of 10.45 +/- 0.88, and median years follow-up of 2.7 (1.1, 5.2). There were five deaths (2.8%), no transplants or VADs, 25 arrhythmias (14.8%), 22 CV hospitalizations (13%), and 39 composites (23.1%). Lower mean HFSS was observed for patients who died (9.6 +/- 0.83 vs. 10.5 +/- 0.87, P = .02), arrhythmia requiring treatment (10.0 +/- 0.70 vs. 10.5 +/- 0.89, P = .005), CV hospitalizations (9.9 +/- 0.73 vs. 10.5 +/- 0.88, P = .002), and the composite (10.0 +/- 0.70 vs. 10.6 +/- 0.89, P < .001). The positive and negative predictive values of HFSS <10.4 for the composite were 34% and 88% respectively, with sensitivity and specificity 74% and 56%. ConclusionsAlthough a low HFSS was significantly associated with outcomes, it did not adequately risk stratify adults with CHD, whose heterogeneous pathophysiology differs from that of the acquired heart failure population. Further studies are warranted to provide a more accurate prognosis. C1 [Lin, Elaine Y.; Lui, George K.] Montefiore Med Ctr, Dept Med, Div Cardiol, Bronx, NY 10467 USA. [Cohen, Hillel W.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Bhatt, Ami B.; Stefanescu, Ada; Dudzinski, David; Yeh, Doreen DeFaria; Johnson, Jacob] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Inst Heart Vasc & Stroke Care, Boston, MA USA. [Lui, George K.] Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA. RP Lin, EY (reprint author), New York Hosp Queens, 56-45 Main St,WA 200, Flushing, NY 11355 USA. EM tingtinglin@gmail.com OI Stefanescu Schmidt, Ada/0000-0002-5692-2616 FU National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH), Bethesda, MD [1 UL1 TR001073-01, 1 TL1 TR001072-01, 1 KL2 TR001071-01] FX This publication was supported in part by the CTSA Grant 1 UL1 TR001073-01, 1 TL1 TR001072-01, and 1 KL2 TR001071-01 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH), Bethesda, MD. NR 22 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-079X EI 1747-0803 J9 CONGENIT HEART DIS JI Congenit. Heart Dis. PD SEP-OCT PY 2015 VL 10 IS 5 BP 387 EP 395 DI 10.1111/chd.12229 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CT6HF UT WOS:000362913400011 PM 25358483 ER PT J AU Kilbaugh, TJ Karlsson, M Byro, M Bebee, A Ralston, J Sullivan, S Duhaime, AC Hansson, MJ Elmer, E Margulies, SS AF Kilbaugh, Todd J. Karlsson, Michael Byro, Melissa Bebee, Ashley Ralston, Jill Sullivan, Sarah Duhaime, Ann-Christine Hansson, Magnus J. Elmer, Eskil Margulies, Susan S. TI Mitochondrial bioenergetic alterations after focal traumatic brain injury in the immature brain SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Pediatric traumatic brain injury; Mitochondria; Axonal injury; Bioenergetics; Contusion; Swine ID MATURATION-DEPENDENT RESPONSE; ELECTRON-TRANSPORT CHAIN; COMMON DATA ELEMENTS; METABOLIC CRISIS; RAT-BRAIN; POSTNATAL-DEVELOPMENT; CEREBRAL-ISCHEMIA; CORTICAL IMPACT; UNITED-STATES; AXONAL INJURY AB Traumatic brain injury (TBI) is one of the leading causes of death in children worldwide. Emerging evidence suggests that alterations in mitochondrial function are critical components of secondary injury cascade initiated by TBI that propogates neurodegeneration and limits neuroregeneration. Unfortunately, there is very little known about the cerebral mitochondrial bioenergetic response from the immature brain triggered by traumatic biomechanical forces. Therefore, the objective of this study was to perform a detailed evaluation of mitochondrial bioenergetics using high-resolution respirometry in a high-fidelity large animal model of focal controlled cortical impact injury (CCI) 24 h post-injury. This novel approach is directed at analyzing dysfunction in electron transport, ADP phosphorylation and leak respiration to provide insight into potential mechanisms and possible interventions for mitochondrial dysfunction in the immature brain in focal TBI by delineating targets within the electron transport system (ETS). Development and application of these methodologies have several advantages, and adds to the interpretation of previously reported techniques, by having the added benefit that any toxins or neurometabolites present in the ex-vivo samples are not removed during the mitochondrial isolation process, and simulates the in situ tricarboxylic acid (TCA) cycle by maximizing key substrates for convergent flow of electrons through both complexes I and II To investigate alterations in mitochondrial function after CCI, ipsilateral tissue near the focal impact site and tissue from the corresponding contralateral side were examined. Respiration per mg of tissue was also related to citrate synthase activity (CS) and calculated flux control ratios (FCR), as an attempt to control for variability in mitochondrial content. Our biochemical analysis of complex interdependent pathways of electron flow through the electron transport system, by most measures, reveals a bilateral decrease in complex I-driven respiration and an increase in complex II-driven respiration 24 h after focal TBI. These alterations in convergent electron flow though both complex I and II-driven respiration resulted in significantly lower maximal coupled and uncoupled respiration in the ipsilateral tissue compared to the contralateral side, for all measures. Surprisingly, increases in complex II and complex IV activities were most pronounced in the contralateral side of the brain from the focal injury, and where oxidative phosphoryladon was increased significantly compared to sham values. We conclude that 24 h after focal TBI in the immature brain, there are significant alterations in cerebral mitochondrial bioenergetics, with pronounced increases in complex II and complex IV respiration in the contralateral hemisphere. These alterations in mitochondrial bioenergetics present multiple targets for therapeutic intervention to limit secondary brain injury and support recovery. (C) 2015 Elsevier Inc. All rights reserved. C1 [Kilbaugh, Todd J.] Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, Anesthesiol & Crit Care Med, Philadelphia, PA 19104 USA. [Karlsson, Michael; Hansson, Magnus J.; Elmer, Eskil] Lund Univ, Dept Clin Sci, Mitochondrial Med, SE-22184 Lund, Sweden. [Byro, Melissa; Bebee, Ashley; Ralston, Jill; Sullivan, Sarah; Margulies, Susan S.] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. [Duhaime, Ann-Christine] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Kilbaugh, TJ (reprint author), 34th & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM kilbaugh@chop.edu; michael.karlsson@med.lu.se; melissa.byro@gmail.com; ashley.n.durban@gmail.com; ralstonjm@gmail.com; sarahsul@seas.upenn.edu; aduhaime@partners.org; magnus.hansson@med.lu.se; eskil.elmer@med.lu.se; margulie@seas.upenn.edu RI Elmer, Eskil/F-9341-2014; OI Elmer, Eskil/0000-0001-7901-1826; Hansson, Magnus/0000-0002-0201-0638; Kilbaugh, Todd/0000-0002-4959-3092 FU NIH [UO1 NS069545]; Endowed Chair of Critical Care Medicine at the Children's Hospital of Philadelphia; Stephenson Fund Department of Bioengineering the University of Pennsylvania FX The authors would like to thank Albana Shahini and Saori Morota for their invaluable technical support. The Oroboros Oxygraph used in the study was a loan from NeuroVive Pharmaceutical AB, Lund Sweden. Studies were supported by the NIH UO1 NS069545, Endowed Chair of Critical Care Medicine at the Children's Hospital of Philadelphia, and Stephenson Fund Department of Bioengineering the University of Pennsylvania. NR 57 TC 5 Z9 6 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 EI 1090-2430 J9 EXP NEUROL JI Exp. Neurol. PD SEP PY 2015 VL 271 BP 136 EP 144 DI 10.1016/j.expneurol.2015.05.009 PG 9 WC Neurosciences SC Neurosciences & Neurology GA CT2JG UT WOS:000362627200015 PM 26028309 ER PT J AU Akthar, S Patel, DF Beale, RC Peiro, T Xu, X Gaggar, A Jackson, PL Blalock, JE Lloyd, CM Snelgrove, RJ AF Akthar, Samia Patel, Dhiren F. Beale, Rebecca C. Peiro, Teresa Xu, Xin Gaggar, Amit Jackson, Patricia L. Blalock, J. Edwin Lloyd, Clare M. Snelgrove, Robert J. TI Matrikines are key regulators in modulating the amplitude of lung inflammation in acute pulmonary infection SO NATURE COMMUNICATIONS LA English DT Article ID LEUKOTRIENE A(4) HYDROLASE; EXTRACELLULAR-MATRIX DEGRADATION; ALVEOLAR MACROPHAGE PHAGOCYTOSIS; SMOKE-INDUCED EMPHYSEMA; KLEBSIELLA-PNEUMONIAE; DEFICIENT MICE; NEUTROPHIL CHEMOATTRACTANT; TRYPANOSOMA-CRUZI; HOST-DEFENSE; B-4 AB Bioactive matrix fragments (matrikines) have been identified in a myriad of disorders, but their impact on the evolution of airway inflammation has not been demonstrated. We recently described a pathway where the matrikine and neutrophil chemoattractant proline-glycine-proline (PGP) could be degraded by the enzyme leukotriene A(4) hydrolase (LTA(4)H). LTA(4)H classically functions in the generation of pro-inflammatory leukotriene B-4, thus LTA(4)H exhibits opposing pro- and anti-inflammatory activities. The physiological significance of this secondary anti-inflammatory activity remains unknown. Here we show, using readily resolving pulmonary inflammation models, that loss of this secondary activity leads to more pronounced and sustained inflammation and illness owing to PGP accumulation. PGP elicits an exacerbated neutrophilic inflammation and protease imbalance that further degrades the extracellular matrix, generating fragments that perpetuate inflammation. This highlights a critical role for the secondary anti-inflammatory activity of LTA(4)H and thus has consequences for the generation of global LTA(4)H inhibitors currently being developed. C1 [Akthar, Samia; Patel, Dhiren F.; Beale, Rebecca C.; Peiro, Teresa; Lloyd, Clare M.; Snelgrove, Robert J.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Leukocyte Biol Sect, London SW7 2AZ, England. [Xu, Xin; Gaggar, Amit; Jackson, Patricia L.; Blalock, J. Edwin] Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL USA. [Xu, Xin; Gaggar, Amit; Jackson, Patricia L.; Blalock, J. Edwin] Univ Alabama Birmingham, Lung Hlth Ctr, Dept Med, Birmingham, AL USA. [Gaggar, Amit] Univ Alabama Birmingham, Gregory Fleming James Cyst Fibrosis Ctr, Birmingham, AL 35294 USA. [Gaggar, Amit] Univ Alabama Birmingham, Program Protease & Matrix Biol, Birmingham, AL 35294 USA. [Gaggar, Amit; Blalock, J. Edwin] Birmingham VA Med Ctr, Birmingham, AL 35294 USA. RP Snelgrove, RJ (reprint author), Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Leukocyte Biol Sect, London SW7 2AZ, England. EM robert.snelgrove@imperial.ac.uk OI Blalock, J. Edwin/0000-0001-5303-8123 FU National Heart, Lung and Blood Institute [HL07783, HL110950, HL114439, HL102371-A1]; NIH [RR19231, P30CA13148, P50AT00277, U54CA100949, P30AR050948, P30DK740380]; Marie Curie Intra European Fellowship within the 7th European Community Framework Programme (FP7-PEOPLE-IEF) [627374] FX R.J.S. is a Wellcome Trust Career Development Fellow (095707/Z/11/Z). C.M.L. is a Wellcome Trust Senior Fellow in Basic Biomedical Sciences (087618/Z/08/Z). T.P. is supported by a Marie Curie Intra European Fellowship within the 7th European Community Framework Programme (FP7-PEOPLE-2013-IEF No. 627374). The National Heart, Lung and Blood Institute funds J.E.B. (HL07783, HL110950 and HL114439) and A.G. (HL102371-A1). The UAB Lung Health Center Pulmonary Proteomics Laboratory is funded through the NIH (RR19231, P30CA13148, P50AT00277, U54CA100949, P30AR050948 and P30DK740380). We would like to thank Dr Anna Caldwell and the Centre of Excellence for Mass Spectrometry at King's College London for the use of equipment and technical assistance. NR 70 TC 5 Z9 5 U1 2 U2 3 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 SEP PY 2015 VL 6 AR 8423 DI 10.1038/ncomms9423 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT9MC UT WOS:000363140200001 PM 26400771 ER PT J AU Day, FR Hinds, DA Tung, JY Stolk, L Styrkarsdottir, U Saxena, R Bjonnes, A Broer, L Dunger, DB Halldorsson, BV Lawlor, DA Laval, G Mathieson, I McCardle, WL Louwers, Y Meun, C Ring, S Scott, RA Sulem, P Uitterlinden, AG Wareham, NJ Thorsteinsdottir, U Welt, C Stefansson, K Laven, JSE Ong, KK Perry, JRB AF Day, Felix R. Hinds, David A. Tung, Joyce Y. Stolk, Lisette Styrkarsdottir, Unnur Saxena, Richa Bjonnes, Andrew Broer, Linda Dunger, David B. Halldorsson, Bjarni V. Lawlor, Debbie A. Laval, Guillaume Mathieson, Iain McCardle, Wendy L. Louwers, Yvonne Meun, Cindy Ring, Susan Scott, Robert A. Sulem, Patrick Uitterlinden, Andre G. Wareham, Nicholas J. Thorsteinsdottir, Unnur Welt, Corrine Stefansson, Kari Laven, Joop S. E. Ong, Ken K. Perry, John R. B. TI Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome SO NATURE COMMUNICATIONS LA English DT Article ID GENOME-WIDE ASSOCIATION; EUROPEAN ANCESTRY; INSULIN-RESISTANCE; CHROMOSOME 2P16.3; SYNDROME RISK; VARIANTS; WOMEN; METAANALYSIS; CANCER; LOCI AB Polycystic ovary syndrome (PCOS) is the most common reproductive disorder in women, yet there is little consensus regarding its aetiology. Here we perform a genome-wide association study of PCOS in up to 5,184 self-reported cases of White European ancestry and 82,759 controls, with follow-up in a further similar to 2,000 clinically validated cases and similar to 100,000 controls. We identify six signals for PCOS at genome-wide statistical significance (P<5 x 10(-8)), in/near genes ERBB4/HER4, YAP1, THADA, FSHB, RAD50 and KRR1. Variants in/near three of the four epidermal growth factor receptor genes (ERBB2/HER2, ERBB3/HER3 and ERBB4/HER4) are associated with PCOS at or near genome-wide significance. Mendelian randomization analyses indicate causal roles in PCOS aetiology for higher BMI (P = 2.5 x 10(-9)), higher insulin resistance (P = 6 x 10(-4)) and lower serum sex hormone binding globulin concentrations (P = 5 x 10(-4)). Furthermore, genetic susceptibility to later menopause is associated with higher PCOS risk (P = 1.6 x 10(-8)) and PCOS-susceptibility alleles are associated with higher serum anti-Mullerian hormone concentrations in girls (P = 8.9 x 10(-5)). This large-scale study implicates an aetiological role of the epidermal growth factor receptors, infers causal mechanisms relevant to clinical management and prevention, and suggests balancing selection mechanisms involved in PCOS risk. C1 [Day, Felix R.; Scott, Robert A.; Wareham, Nicholas J.; Ong, Ken K.; Perry, John R. B.] Univ Cambridge, Sch Clin Med, Addenbrookes Hosp, MRC Epidemiol Unit, Cambridge CB2 0QQ, England. [Hinds, David A.; Tung, Joyce Y.] 23andMe Inc, Mountain View, CA 94043 USA. [Stolk, Lisette; Broer, Linda; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands. [Styrkarsdottir, Unnur; Halldorsson, Bjarni V.; Sulem, Patrick; Thorsteinsdottir, Unnur; Stefansson, Kari] DeCODE Genet Amgen, IS-101 Reykjavik, Iceland. [Saxena, Richa; Bjonnes, Andrew] Massachusetts Gen Hosp, Dept Anaesthesia, Boston, MA 02114 USA. [Saxena, Richa; Bjonnes, Andrew] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Dunger, David B.; Ong, Ken K.] Univ Cambridge, Sch Clin Med, Dept Paediat, Cambridge CB2 0QQ, England. [Halldorsson, Bjarni V.] Reykjavik Univ, Sch Sci & Engn, Inst Biomed & Neural Engn, IS-101 Reykjavik, Iceland. [Lawlor, Debbie A.; Ring, Susan] Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England. [Lawlor, Debbie A.; McCardle, Wendy L.; Ring, Susan] Univ Bristol, Sch Social & Community Med, Bristol BS8 2BN, Avon, England. [Laval, Guillaume] Inst Pasteur, CNRS, Human Evolutionary Genet, URA3012, F-75724 Paris 15, France. [Mathieson, Iain] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Louwers, Yvonne; Meun, Cindy; Laven, Joop S. E.] Erasmus MC, Dept Obstet & Gynaecol, Div Reprod Med, NL-3015 GE Rotterdam, Netherlands. [Thorsteinsdottir, Unnur; Stefansson, Kari] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland. [Welt, Corrine] Univ Utah, Div Endocrinol Metab & Diabet, Sch Med, Salt Lake City, UT 84112 USA. RP Ong, KK (reprint author), Univ Cambridge, Sch Clin Med, Addenbrookes Hosp, MRC Epidemiol Unit, Box 285 Inst Metab Sci,Cambridge Biomed Campus, Cambridge CB2 0QQ, England. EM Ken.ong@mrc-epid.cam.ac.uk; john.perry@mrc-epid.cam.ac.uk OI Day, Felix/0000-0003-3789-7651; Dunger, Professor David/0000-0002-2566-9304; Halldorsson, Bjarni/0000-0003-0756-0767; Welt, Corrine/0000-0002-8219-5504; Lawlor, Debbie A/0000-0002-6793-2262 FU Medical Research Council [U106179472, MC_U106179472, U106179471, MC_U106179471]; National Human Genome Research Institute of the National Institutes of Health [R44HG006981]; US National Institute of Health [R01 DK077659]; University of Bristol; UK Medical Research Council [MC_UU_12013/5] FX This work was supported by the Medical Research Council (U106179472, MC_U106179472, U106179471 and MC_U106179471) and the National Human Genome Research Institute of the National Institutes of Health (grant number R44HG006981 to 23andMe). The UK Medical Research Council and Wellcome Trust (092731), together with the University of Bristol, provide core support for the ALSPAC study. AMH assays in ALSPAC were funded with a grant from the US National Institute of Health (R01 DK077659). DAL works in a unit that receives funding from the University of Bristol and the UK Medical Research Council (MC_UU_12013/5). We thank the customers and employees of 23andMe for making this work possible. We are extremely grateful to all of the families who took part in the participating studies. We thank the ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses, and also midwives for supporting recruitment. NR 46 TC 26 Z9 26 U1 5 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 SEP PY 2015 VL 6 AR 8464 DI 10.1038/ncomms9464 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT9NY UT WOS:000363145100001 PM 26416764 ER PT J AU Maekawa, T Hosur, K Abe, T Kantarci, A Ziogas, A Wang, BM Van Dyke, TE Chavakis, T Hajishengallis, G AF Maekawa, Tomoki Hosur, Kavita Abe, Toshiharu Kantarci, Alpdogan Ziogas, Athanasios Wang, Baomei Van Dyke, Thomas E. Chavakis, Triantafyllos Hajishengallis, George TI Antagonistic effects of IL-17 and D-resolvins on endothelial Del-1 expression through a GSK-3 beta-C/EBP beta pathway SO NATURE COMMUNICATIONS LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3; BINDING PROTEIN-BETA; PERIODONTAL-DISEASES; LIPID MEDIATORS; T(H)17 CELLS; IFN-GAMMA; INFLAMMATION; RESOLUTION; PHOSPHORYLATION; MICE AB Del-1 is an endothelial cell-secreted anti-inflammatory protein. In humans and mice, Del-1 expression is inversely related to that of IL-17, which inhibits Del-1 through hitherto unidentified mechanism(s). Here we show that IL-17 downregulates human endothelial cell expression of Del-1 by targeting a critical transcription factor, C/EBP beta. Specifically, IL-17 causes GSK-3 beta-dependent phosphorylation of C/EBP beta, which is associated with diminished C/EBP beta binding to the Del-1 promoter and suppressed Del-1 expression. This inhibitory action of IL-17 can be reversed at the GSK-3 beta level by PI3K/Akt signalling induced by D-resolvins. The biological relevance of this regulatory network is confirmed in a mouse model of inflammatory periodontitis. Intriguingly, resolvin-D1 (RvD1) confers protection against IL-17-driven periodontal bone loss in a Del-1-dependent manner, indicating an RvD1-Del-1 axis against IL-17-induced pathological inflammation. The dissection of signalling pathways regulating Del-1 expression provides potential targets to treat inflammatory diseases associated with diminished Del-1 expression, such as periodontitis and multiple sclerosis. C1 [Maekawa, Tomoki; Hosur, Kavita; Abe, Toshiharu; Wang, Baomei; Hajishengallis, George] Univ Penn, Dept Microbiol, Penn Dent Med, Philadelphia, PA 19104 USA. [Maekawa, Tomoki] Niigata Univ, Grad Sch Med & Dent Sci, Res Ctr Adv Oral Sci, Chuo Ku, Niigata 9518514, Japan. [Kantarci, Alpdogan; Van Dyke, Thomas E.] Forsyth Inst, Ctr Periodontol, Dept Appl Oral Sci, Cambridge, MA 02142 USA. [Ziogas, Athanasios; Chavakis, Triantafyllos] Tech Univ Dresden, Dept Clin Pathobiochem, D-01307 Dresden, Germany. [Ziogas, Athanasios; Chavakis, Triantafyllos] Tech Univ Dresden, Inst Clin Chem, D-01307 Dresden, Germany. [Ziogas, Athanasios; Chavakis, Triantafyllos] Tech Univ Dresden, Lab Med, D-01307 Dresden, Germany. RP Hajishengallis, G (reprint author), Univ Penn, Dept Microbiol, Penn Dent Med, 240 S 40th St, Philadelphia, PA 19104 USA. EM geoh@upenn.edu FU NIH [DE015254, DE021685, DE024716, AI068730, DE020906, DE015566, DE019938]; Deutsche Forschungsgemeinschaft [CH279/5-1, CH279/6-2, SFB-TR 127]; German Federal Government; European Research Council (ENDHOMRET); German State Government FX This study was supported by grants from the NIH (DE015254, DE021685, DE024716 and AI068730 to G.H.; DE020906 to A.K.; DE015566 and DE019938 to T.V.D.), the Deutsche Forschungsgemeinschaft (CH279/5-1, CH279/6-2 and SFB-TR 127 Project A3 to T.C.), by funding of the Excellence Initiative by the German Federal and State Governments' (Institutional Strategy, measure 'support the best' of the Technische Universitat Dresden to T.C.) and the European Research Council (ENDHOMRET to T.C.). NR 49 TC 11 Z9 11 U1 5 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD SEP PY 2015 VL 6 AR 8272 DI 10.1038/ncomms9272 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CT7UC UT WOS:000363019000002 PM 26374165 ER PT J AU Fatemi, G Fang, MA Breuer, P Cherniak, PE Gentili, A Hanlon, JT Karp, JF Morone, NE Rodriguez, E Rossi, MI Schmader, K Weiner, DK AF Fatemi, Gita Fang, Meika A. Breuer, Paula Cherniak, Paul E. Gentili, Angela Hanlon, Joseph T. Karp, Jordan F. Morone, Natalia E. Rodriguez, Eric Rossi, Michelle I. Schmader, Kenneth Weiner, Debra K. TI Deconstructing Chronic Low Back Pain in the Older Adult-Step by Step Evidence and Expert-Based Recommendations for Evaluation and Treatment Part III: Fibromyalgia Syndrome SO PAIN MEDICINE LA English DT Review DE Fibromyalgia; Low Back Pain; Elderly; Chronic Pain; Back Pain ID OF-RHEUMATOLOGY 1990; AEROBIC EXERCISE; DOUBLE-BLIND; MULTICENTER TRIAL; RANDOMIZED-TRIAL; SELF-MANAGEMENT; TAI CHI; PREVALENCE; SLEEP; PLACEBO AB Objective. To present the third in a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults. The series presents CLBP as a syndrome, a final common pathway for the expression of multiple contributors rather than a disease localized exclusively to the lumbosacral spine. Each article addresses one of 12 important contributors to pain and disability in older adults with CLBP. This article focuses on fibromyalgia syndrome (FMS). Methods. A modified Delphi approach was used to create the evaluation and treatment algorithm, the table discussing the rationale behind each of the algorithm components, and the stepped-care drug recommendations. The team involved in the creation of these materials consisted of a principal investigator, a 5-member content expert panel, and a 9-member primary care panel. The evaluation and treatment recommendations were based on availability of medications and other resources within the Veterans Health Administration (VHA) facilities. However, non-VHA panelists were also involved in the development of these materials, which can be applied to both VA and civilian settings. The illustrative clinical case was taken from the clinical practice of the principal investigator. Results. Following expert consultations and a review of the literature, we developed an evaluation and treatment algorithm with supporting materials to aid in the care of older adults with CLBP who have concomitant FMS. A case is presented that demonstrates the complexity of pain evaluation and management in older patients with CLBP and concomitant FMS. Conclusions. Recognition of FMS as a common contributor to CLBP in older adults and initiating treatment targeting both FMS and CLBP may lead to improved outcomes in pain and disability. C1 [Fatemi, Gita; Fang, Meika A.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Fatemi, Gita; Fang, Meika A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Breuer, Paula] Univ Pittsburgh, Med Ctr, Ctr Rehab Serv, Pittsburgh, PA USA. [Cherniak, Paul E.] Univ Miami, Miller Sch Med, Div Geriatr & Palliat Med, Miami, FL 33136 USA. [Cherniak, Paul E.] Bruce W Carter Miami VA Med Ctr, Miami, FL USA. [Gentili, Angela] Virginia Commonwealth Univ Hlth Syst, Richmond, VA USA. [Gentili, Angela] Hunter Holmes McGuire VA Med Ctr, Richmond, VA USA. [Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Dept Geriatr Med, Sch Med, Pittsburgh, PA USA. [Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Sch Med, Pittsburgh, PA 15261 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Sch Med, Pittsburgh, PA 15260 USA. [Hanlon, Joseph T.; Morone, Natalia E.; Rossi, Michelle I.; Weiner, Debra K.] Vet Affairs Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA USA. [Hanlon, Joseph T.] VA Pittsburgh Hlth Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Karp, Jordan F.; Weiner, Debra K.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Karp, Jordan F.; Weiner, Debra K.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA USA. [Karp, Jordan F.; Weiner, Debra K.] Univ Pittsburgh, Clin & Translat Sci Inst, Pittsburgh, PA USA. [Morone, Natalia E.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Ctr Res Hlth Care, Pittsburgh, PA USA. [Morone, Natalia E.] Univ Pittsburgh, Sch Med, Clin & Translat Sci Inst, Pittsburgh, PA USA. [Rodriguez, Eric] Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA USA. [Rossi, Michelle I.; Weiner, Debra K.] Univ Pittsburgh, Sch Med, Dept Med, Div Geriatr Med, Pittsburgh, PA 15213 USA. [Schmader, Kenneth] Durham VA Med Ctr, GRECC, Durham, NC USA. [Schmader, Kenneth] Duke Univ, Med Ctr, Dept Med, Div Geriatr, Durham, NC 27710 USA. RP Weiner, DK (reprint author), VA Pittsburgh Healthcare Syst, Univ Dr,Bldg 30,00GR, Pittsburgh, PA 15240 USA. EM debra.weiner@va.gov FU NIA NIH HHS [K07 AG033174, P30 AG024827, T32 AG021885] NR 53 TC 0 Z9 0 U1 3 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD SEP PY 2015 VL 16 IS 9 BP 1709 EP 1719 DI 10.1111/pme.12863 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA CT5YR UT WOS:000362887700007 PM 26272644 ER PT J AU Solow, EB Yu, F Thiele, GM Sokolove, J Robinson, WH Pruhs, ZM Michaud, KD Erickson, AR Sayles, H Kerr, GS Gaffo, AL Caplan, L Davis, LA Cannon, GW Reimold, AM Baker, J Schwab, P Anderson, DR Mikuls, TR AF Solow, E. Blair Yu, Fang Thiele, Geoffrey M. Sokolove, Jeremy Robinson, William H. Pruhs, Zachary M. Michaud, Kaleb D. Erickson, Alan R. Sayles, Harlan Kerr, Gail S. Gaffo, Angelo L. Caplan, Liron Davis, Lisa A. Cannon, Grant W. Reimold, Andreas M. Baker, Joshua Schwab, Pascale Anderson, Daniel R. Mikuls, Ted R. TI Vascular calcifications on hand radiographs in rheumatoid arthritis and associations with autoantibodies, cardiovascular risk factors and mortality SO RHEUMATOLOGY LA English DT Article DE rheumatoid arthritis; vascular calcifications; hand radiographs; anti-citrullinated protein autoantibodies; mortality ID SMOOTH-MUSCLE-CELLS; DISEASE-ACTIVITY; CORONARY ATHEROSCLEROSIS; ARTERIAL CALCIFICATION; MYOCARDIAL-INFARCTION; ALPHA THERAPY; BONE LOSS; OSTEOPOROSIS; MICE; INTERLEUKIN-4 AB Objective. To examine whether vascular calcifications on hand films in RA might aid in determining mortality risk. Methods. Hand radiographs from 906 RA patients were scored as positive or negative for vascular calcifications. Patient characteristics associated with vascular calcifications were assessed using multivariable logistic regression, and associations with mortality were examined using Cox proportional hazards regression. Cytokines and multiplex ACPA were measured in both groups. Results. A total of 99 patients (11%) demonstrated radiographic vascular calcifications. Factors independently associated with vascular calcifications included diabetes [odds ratio (OR) 2.85; 95% CI 1.43, 5.66], cardiovascular disease at enrolment (OR 2.48; 95% CI 1.01, 6.09), prednisone use (OR 1.90; 95% CI 1.25, 2.91), current smoking (OR 0.06; 95% CI 0.01, 0.23) and former smoking (OR 0.36; 95% CI 0.27, 0.48) vs never smoking. In cytokine and ACPA subtype analysis, IL-4 and anti-citrullinated apolipoprotein E were significantly increased in patients with vascular calcifications in fully adjusted multivariable models. After multivariable adjustment, vascular calcifications were associated with an increase in all-cause mortality (hazard ratio 1.41; 95% CI 1.12, 1.78; P = 0.004). Conclusion. Vascular calcifications on hand radiographs were independently associated with increased all-cause mortality in RA. Mechanisms underpinning the associations of IL-4 and select ACPA with vascular calcifications and their utility as biomarkers predictive of cardiovascular disease risk in RA merit further study. C1 [Solow, E. Blair; Reimold, Andreas M.] UT Southwestern, Div Rheumat Dis, Dallas, TX USA. [Yu, Fang] Univ Nebraska Med Ctr, Coll Publ Hlth, Dept Biostat, Omaha, NE USA. [Thiele, Geoffrey M.; Pruhs, Zachary M.; Michaud, Kaleb D.; Erickson, Alan R.; Sayles, Harlan; Mikuls, Ted R.] Omaha Vet Affairs Med Ctr, Div Rheumatol & Immunol, Omaha, NE 68198 USA. [Sokolove, Jeremy; Robinson, William H.] VA Palo Alto Hlth Care Syst, Div Rheumatol, Palo Alto, CA USA. [Michaud, Kaleb D.] Natl Data Bank Rheumat Dis, Wichita, KS USA. [Kerr, Gail S.] Vet Affairs Med Ctr, Dept Med, Washington, DC 20422 USA. [Gaffo, Angelo L.] Birmingham Vet Affairs Med Ctr, Dept Med, Birmingham, AL USA. [Caplan, Liron; Davis, Lisa A.] Denver Vet Affairs Med Ctr, Div Rheumatol, Denver, CO USA. [Cannon, Grant W.] George Wahlen Vet Affairs Med Ctr, Div Rheumatol, Salt Lake City, UT USA. [Reimold, Andreas M.] Dallas Vet Affairs Med Ctr, Div Rheumatol, Dallas, TX USA. [Baker, Joshua] Philadelphia Vet Affairs Med Ctr, Div Rheumatol, Philadelphia, PA USA. [Schwab, Pascale] Portland VA Med Ctr, Div Rheumatol, Portland, OR USA. [Anderson, Daniel R.] Univ Nebraska Med Ctr, Div Cardiol, Omaha, NE USA. RP Mikuls, TR (reprint author), Omaha Vet Affairs Med Ctr, Div Rheumatol & Immunol, 986270 Nebraska Med Ctr, Omaha, NE 68198 USA. EM tmikuls@unmc.edu FU Nebraska Arthritis Outcomes Research Centre at the University of Nebraska Medical Centre FX This work was supported by the Nebraska Arthritis Outcomes Research Centre at the University of Nebraska Medical Centre. NR 45 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 EI 1462-0332 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD SEP PY 2015 VL 54 IS 9 BP 1587 EP 1595 DI 10.1093/rheumatology/kev027 PG 9 WC Rheumatology SC Rheumatology GA CT5KL UT WOS:000362848500009 PM 25854268 ER PT J AU Belizaire, R Sykes, DB Chen, YBA Spitzer, TR Makar, RS AF Belizaire, Roger Sykes, David B. Chen, Yi-Bin A. Spitzer, Thomas R. Makar, Robert S. TI Difficulties in hematopoietic progenitor cell collection from a patient with TEMPI syndrome and severe iatrogenic iron deficiency SO TRANSFUSION LA English DT Article ID BLOOD STEM-CELLS; MULTIPLE-MYELOMA; TRANSPLANTATION; LEUKAPHERESIS; MOBILIZATION; INFUSION; DISEASE; BORTEZOMIB; EFFICACY; REMOVAL AB BACKGROUND: Collection of hematopoietic progenitor cells by apheresis (HPC-A) requires separation of cells by density. Previous studies highlighted the challenges of HPC-A collection from patients with abnormal red blood cells (RBCs). TEMPI syndrome is a recently described condition defined by teleangiectasias, elevated erythropoietin and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting. Patients with TEMPI syndrome have responded to therapies used to treat plasma cell dyscrasias and may benefit from autologous HPC transplantation. We report HPC-A collection from a patient with TEMPI syndrome that was complicated by severe iron deficiency. STUDY DESIGN AND METHODS: The patient received granulocyte-colony-stimulating factor (G-CSF) and plerixafor for HPC mobilization and underwent 3 days of HPC-A collection. RESULTS: The patient presented for collection with a microcytic erythrocytosis. Over 3 days, approximately 50 L of whole blood was processed, and 2 x 10(8) CD34+ cells were collected (2.8 x 10(6) CD34+ cells/kg). The mean collection efficiency (CE), percentage of mononuclear cells, hematocrit (Hct), and RBC count were 18%, 90%, 14%, and 9 x 10(11), respectively. Altering collection variables to avoid RBC contamination reduced CE. Ficoll preparations of the products after freeze-thaw showed RBC contamination and hemolysis. Postthaw viability exceeded 95%. The products were not RBC reduced or washed. There were no adverse reactions during or after infusion. CONCLUSIONS: HPC-A collection from a patient with TEMPI syndrome was complicated by microcytic erythrocytosis, leading to RBC contamination and hemolysis in the product. Adequate HPCs were collected and the patient tolerated infusion without RBC depletion or washing. Our report highlights difficulties of HPC-A collection from iron-deficient patients. C1 [Belizaire, Roger] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Sykes, David B.; Chen, Yi-Bin A.; Spitzer, Thomas R.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Makar, Robert S.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Makar, RS (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, 55 Fruit St,GRJ 2-206C, Boston, MA 02114 USA. EM rmakar@partners.org NR 21 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD SEP PY 2015 VL 55 IS 9 BP 2142 EP 2148 DI 10.1111/trf.13125 PG 7 WC Hematology SC Hematology GA CT6HO UT WOS:000362914300014 PM 25911963 ER PT J AU Spitalnik, SL Triulzi, D Devine, DV Dzik, WH Eder, AF Gernsheimer, T Josephson, CD Kor, DJ Luban, NLC Roubinian, NH Mondoro, T Welniak, LA Zou, SM Glynn, S AF Spitalnik, Steven L. Triulzi, Darrell Devine, Dana V. Dzik, Walter H. Eder, Anne F. Gernsheimer, Terry Josephson, Cassandra D. Kor, Daryl J. Luban, Naomi L. C. Roubinian, Nareg H. Mondoro, Traci Welniak, Lisbeth A. Zou, Shimian Glynn, Simone CA State Sci Transfusion Med Working TI 2015 proceedings of the National Heart, Lung, and Blood Institute's State of the Science in Transfusion Medicine symposium SO TRANSFUSION LA English DT Article; Proceedings Paper CT Meeting on the State of the Science in Transfusion Medicine CY MAR 25-26, 2015 CL Natl Inst Hlth, Bethesda, MD SP Natl Heart Lung & Blood Inst HO Natl Inst Hlth ID SICKLE-CELL-DISEASE; TRAUMA-ASSOCIATED COAGULOPATHY; RANDOMIZED-CLINICAL-TRIAL; CARDIAC-SURGERY; PLATELET TRANSFUSIONS; NONIDENTICAL PLASMA; DRIED PLASMA; STEM-CELLS; MORTALITY; ALLOIMMUNIZATION AB On March 25 and 26, 2015, the National Heart, Lung, and Blood Institute sponsored a meeting on the State of the Science in Transfusion Medicine on the National Institutes of Health (NIH) campus in Bethesda, Maryland, which was attended by a diverse group of 330 registrants. The meeting's goal was to identify important research questions that could be answered in the next 5 to 10 years and which would have the potential to transform the clinical practice of transfusion medicine. These questions could be addressed by basic, translational, and/or clinical research studies and were focused on four areas: the three "classical" transfusion products (i.e., red blood cells, platelets, and plasma) and blood donor issues. Before the meeting, four working groups, one for each area, prepared five major questions for discussion along with a list of five to 10 additional questions for consideration. At the meeting itself, all of these questions, and others, were discussed in keynote lectures, small-group breakout sessions, and large-group sessions with open discourse involving all meeting attendees. In addition to the final lists of questions, provided herein, the meeting attendees identified multiple overarching, cross-cutting themes that addressed issues common to all four areas; the latter are also provided. It is anticipated that addressing these scientific priorities, with careful attention to the overarching themes, will inform funding priorities developed by the NIH and provide a solid research platform for transforming the future practice of transfusion medicine. C1 [Spitalnik, Steven L.] Columbia Univ, Dept Pathol & Cell Biol, Med Ctr, New York Presbyterian Hosp, New York, NY 10032 USA. [Triulzi, Darrell] Univ Pittsburgh, Inst Transfus Med, Pittsburgh, PA USA. [Triulzi, Darrell] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. [Devine, Dana V.] Univ British Columbia, Canadian Blood Serv, Vancouver, BC V5Z 1M9, Canada. [Devine, Dana V.] Univ British Columbia, Ctr Blood Res, Vancouver, BC V5Z 1M9, Canada. [Dzik, Walter H.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Dzik, Walter H.] Harvard Univ, Sch Med, Boston, MA USA. [Eder, Anne F.] Amer Red Cross, Natl Headquarters, Rockville, MD USA. [Gernsheimer, Terry] Univ Washington, Dept Med, Seattle, WA USA. [Josephson, Cassandra D.] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Kor, Daryl J.] Mayo Clin, Coll Med, Dept Anesthesiol, Rochester, MN USA. [Luban, Naomi L. C.] George Washington Univ, Sch Med, Div Lab Med, Ctr Canc & Blood Dis,Childrens Natl Hlth Syst, Washington, DC USA. [Luban, Naomi L. C.] George Washington Univ, Sch Med, Dept Pediat, Washington, DC 20052 USA. [Roubinian, Nareg H.] Univ Calif San Francisco, Blood Syst Res Inst, San Francisco, CA 94143 USA. [Roubinian, Nareg H.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. [Mondoro, Traci; Welniak, Lisbeth A.; Zou, Shimian; Glynn, Simone] NHLBI, Div Blood Dis & Resources, NIH, Bethesda, MD 20892 USA. RP Spitalnik, SL (reprint author), Columbia Univ, Dept Pathol & Cell Biol, Med Ctr, New York Presbyterian Hosp, 630 West 168th St,Room P&S 14-434, New York, NY 10032 USA. EM ss2479@cumc.columbia.edu RI Karam, Oliver/N-6216-2014; Dumont, Larry/B-3994-2011; Li, Renhao/B-1257-2012; OI Karam, Oliver/0000-0001-6606-1736; Dumont, Larry/0000-0002-1715-0748; Li, Renhao/0000-0002-5806-5080; Spitalnik, Steven/0000-0002-8528-4561 FU NHLBI NIH HHS [P01 HL107146, R01 HL089224, R01 HL115557, R01 HL121232] NR 56 TC 20 Z9 20 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD SEP PY 2015 VL 55 IS 9 BP 2282 EP 2290 DI 10.1111/trf.13250 PG 9 WC Hematology SC Hematology GA CT6HO UT WOS:000362914300028 PM 26260861 ER PT J AU Connor, DM Dhaliwal, G AF Connor, Denise M. Dhaliwal, Gurpreet TI When less is more for the struggling clinical reasoner SO DIAGNOSIS LA English DT Article DE clinical reasoning; deliberate practice; feedback; medical students; remediation ID MEDICAL-EDUCATION; DIFFICULTIES; REMEDIATION; OUTCOMES AB Busy clinician-educators are often tasked with remediating medical students who have deficits in clinical reasoning. In this essay, we share our early experience with providing less feedback and more practice to these trainees. We suggest that front line teachers can streamline their feedback to struggling reasoners by focusing solely on the problem representation and prioritized differential diagnosis of the main problem in their oral presentations and then engaging in repeated loops of feedback until the student achieves competency in real time. By receiving feedback targeted to the assessment alone and employing deliberate practice, struggling students have the opportunity to make concrete improvement during short-term clinical assignments. This remediation approach is feasible for busy clinician-educators and warrants formal study. C1 [Connor, Denise M.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Connor, Denise M.; Dhaliwal, Gurpreet] San Francisco VA Med Ctr, Med Serv, San Francisco, CA 94121 USA. [Connor, Denise M.; Dhaliwal, Gurpreet] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. RP Connor, DM (reprint author), San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. EM denise.connor@ucsf.edu NR 11 TC 0 Z9 0 U1 0 U2 1 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 2194-8011 EI 2194-802X J9 DIAGNOSIS JI Diagnosis PD SEP PY 2015 VL 2 IS 3 BP 159 EP 162 DI 10.1515/dx-2015-0014 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA CT8HV UT WOS:000363056900002 ER PT J AU Nizamoglu, S Lee, KB Gather, MC Kim, KS Jeon, M Kim, S Humar, M Yun, SH AF Nizamoglu, Sedat Lee, Kyung-Bok Gather, Malte C. Kim, Ki Su Jeon, Mijeong Kim, Seonghoon Humar, Matjaz Yun, Seok-Hyun TI A Simple Approach to Biological Single-Cell Lasers Via Intracellular Dyes SO ADVANCED OPTICAL MATERIALS LA English DT Article ID FLUORESCENT-PROBES C1 [Nizamoglu, Sedat; Lee, Kyung-Bok; Gather, Malte C.; Kim, Ki Su; Jeon, Mijeong; Kim, Seonghoon; Humar, Matjaz; Yun, Seok-Hyun] Harvard Univ, Sch Med, Cambridge, MA 02139 USA. [Nizamoglu, Sedat; Lee, Kyung-Bok; Gather, Malte C.; Kim, Ki Su; Jeon, Mijeong; Kim, Seonghoon; Humar, Matjaz; Yun, Seok-Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Cambridge, MA 02139 USA. [Nizamoglu, Sedat] Koc Univ, Dept Elect & Elect Engn, TR-34450 Istanbul, Turkey. [Lee, Kyung-Bok] Korea Basic Sci Inst, Biol Disaster Anal Grp, Daejeon 305806, South Korea. [Gather, Malte C.] Univ St Andrews, SUPA, Sch Phys & Astron, St Andrews KY16 9SS, Fife, Scotland. [Jeon, Mijeong; Kim, Seonghoon] Korea Adv Inst Sci & Technol, Grad Sch Nanosci & Technol WCU, Daejeon 305701, South Korea. [Humar, Matjaz] Jozef Stefan Inst, Condensed Matter Dept, SI-1000 Ljubljana, Slovenia. [Yun, Seok-Hyun] Harvard MIT Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Yun, SH (reprint author), Harvard Univ, Sch Med, 65 Landsdowne St,UP-5, Cambridge, MA 02139 USA. EM syun@hms.harvard.edu RI Humar, Matjaz/I-8862-2012; OI Humar, Matjaz/0000-0003-3338-6723; Gather, Malte/0000-0002-4857-5562 FU National Science Foundation [ECS-1101947]; Military Photomedicine grant from Air Force Office of Scientific Research grant [FA9550-11-1-0331]; Department of Defense; Wellman-Bullock Fellowship; Marie Curie Career Integration Grant within the 7th European Community Framework Programme [631679]; Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme [627274] FX The authors thank Allen Ehrlicher (McGill University) for discussions and providing initial CMFDA samples. This work was supported by a research grant (ECS-1101947) from the National Science Foundation and a Military Photomedicine grant (FA9550-11-1-0331) from Air Force Office of Scientific Research grant and Department of Defense. S.N. also acknowledges the Wellman-Bullock Fellowship and Marie Curie Career Integration Grant within the 7th European Community Framework Programme (631679). M.H. is supported in part by the Marie Curie International Outgoing Fellowship No. 627274 within the 7th European Community Framework Programme. NR 11 TC 4 Z9 4 U1 8 U2 19 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 101161, 69451 WEINHEIM, GERMANY SN 2195-1071 J9 ADV OPT MATER JI Adv. Opt. Mater. PD SEP PY 2015 VL 3 IS 9 BP 1197 EP 1200 DI 10.1002/adom.201500144 PG 4 WC Materials Science, Multidisciplinary; Optics SC Materials Science; Optics GA CT0YO UT WOS:000362524300007 ER PT J AU Sheffrin, M AF Sheffrin, Meera TI Cholinesterase inhibitors cause significant weight loss in patients with dementia SO BRITISH JOURNAL OF HOSPITAL MEDICINE LA English DT News Item C1 Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Med, Div Geriatr, San Francisco, CA 94143 USA. RP Sheffrin, M (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Med, Div Geriatr, San Francisco, CA 94143 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MA HEALTHCARE LTD PI LONDON PA ST JUDES CHURCH, DULWICH ROAD, LONDON SE24 0PB, ENGLAND SN 1750-8460 EI 1759-7390 J9 BRIT J HOSP MED JI Br. J. Hosp. Med. PD SEP PY 2015 VL 76 IS 9 BP 501 EP 501 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CS9AL UT WOS:000362381400005 ER PT J AU Vaickus, LJ Tambouret, RH AF Vaickus, Louis J. Tambouret, Rosemary H. TI Young Investigator Challenge: The Accuracy of the Nuclear-to-Cytoplasmic Ratio Estimation Among Trained Morphologists SO CANCER CYTOPATHOLOGY LA English DT Article DE accuracy; estimate; morphology; morphometry; NC ratio, N; C ratio; nuclear-to-cytoplasmic ratio; nuclear cytoplasmic ratio; visual ID CELLS AB BACKGROUND: The estimation of the nuclear-to-cytoplasmic ratio (N:C ratio) is an important factor in diagnosing atypia and malignancy in pathological specimens, particularly in cytology. Many algorithms for determining malignant potential make reference to specific, decimal N: C ratios without specifying how the ratio should be measured, with the implication that the observer is intended to estimate this ratio by eye. The authors wanted to determine how accurate trained morphologists (including attending pathologists, pathology residents, and cytotechnologists) are at estimating the N: C ratio without a measuring device. METHODS: Two surveys were prepared containing ideal and real cell images of various N: C ratios. Participants were instructed to select their best estimate from a list of decimal ratios. The data were tabulated and analyzed to determine how accurate the estimates were and whether there was any performance difference between ideal and real images. RESULTS: The absolute and percentage deviation from the actual N: C ratio decreased steadily with increasing N: C ratio. Aggregate performance was found to be closely correlated between real and ideal images, although interobserver variation was not significantly different among participants in the real images quiz, but was significantly different on the ideal images quiz. CONCLUSIONS: Trained morphologists make relatively accurate estimations of the N: C ratio and become increasingly more accurate as the depicted N: C ratio increases. This suggests that including N: C ratio decimals as a criteria for the diagnosis of atypia is valid for high N: C ratios. 2015 American Cancer Society. C1 [Vaickus, Louis J.; Tambouret, Rosemary H.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Vaickus, LJ (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren Bldg 2, Boston, MA 02114 USA. EM lvaickus@partners.org NR 7 TC 2 Z9 2 U1 0 U2 2 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 SEP PY 2015 VL 123 IS 9 BP 524 EP 530 DI 10.1002/cncy.21585 PG 7 WC Oncology; Pathology SC Oncology; Pathology GA CT4NS UT WOS:000362784200005 PM 26375883 ER PT J AU Huffman, JC Beale, EE Beach, SR Celano, CM Belcher, AM Moore, SV Suarez, L Gandhi, PU Motiwala, SR Gaggin, H Januzzi, JL AF Huffman, Jeff C. Beale, Eleanor E. Beach, Scott R. Celano, Christopher M. Belcher, Arianna M. Moore, Shannon V. Suarez, Laura Gandhi, Parul U. Motiwala, Shweta R. Gaggin, Hanna Januzzi, James L. TI Design and baseline data from the Gratitude Research in Acute Coronary Events (GRACE) study SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Optimism; Gratitude; Physical activity; Acute coronary syndrome; Coronary artery disease ID RANDOMIZED CONTROLLED-TRIAL; C-REACTIVE PROTEIN; AMERICAN-HEART-ASSOCIATION; BRAIN NATRIURETIC PEPTIDE; INTERCELLULAR-ADHESION MOLECULE-1; PATIENT HEALTH QUESTIONNAIRE-9; HOSPITALIZED CARDIAC PATIENTS; POSITIVE-AFFECT INTERVENTION; PROMOTE PHYSICAL-ACTIVITY; LIFE ORIENTATION TEST AB Background: Positive psychological constructs, especially optimism, have been linked with superior cardiovascular health. However, there has been minimal study of positive constructs in patients with acute coronary syndrome (ACS), despite the prevalence and importance of this condition. Furthermore, few studies have examined multiple positive psychological constructs and multiple cardiac-related outcomes within the same cohort to determine specifically which positive construct may affect a particular cardiac outcome. Materials and methods: The Gratitude Research in Acute Coronary Events (GRACE) study examines the association between optimism/gratitude 2 weeks post-ACS and subsequent clinical outcomes. The primary outcome measure is physical activity at 6 months, measured via accelerometer, and key secondary outcome measures include levels of prognostic biomarkers and rates of nonelective cardiac rehospitalization at 6 months. These relationships will be analyzed using multivariable linear regression, controlling for sociodemographic, medical, and negative psychological factors; associations between baseline positive constructs and subsequent rehospitalizafions will be assessed via Cox regression. Results: Overall, 164 participants enrolled and completed the baseline 2-week assessment; the cohort had a mean age of 61.5 +/- 10.5 years and was 84% men; this was the first ACS for 58% of participants. Conclusion: The GRACE study will determine whether optimism and gratitude are prospectively and independently associated with physical activity and other critical outcomes in the 6 months following an ACS. If these constructs are associated with superior outcomes, this may highlight the importance of these constructs as independent prognostic factors post-ACS. (C) 2015 Elsevier Inc. All rights reserved. C1 [Huffman, Jeff C.; Beach, Scott R.; Celano, Christopher M.; Suarez, Laura; Gandhi, Parul U.; Motiwala, Shweta R.; Gaggin, Hanna; Januzzi, James L.] Harvard Univ, Sch Med, Boston, MA USA. [Huffman, Jeff C.; Beale, Eleanor E.; Beach, Scott R.; Celano, Christopher M.; Moore, Shannon V.; Suarez, Laura] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Belcher, Arianna M.; Gandhi, Parul U.; Gaggin, Hanna; Januzzi, James L.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Motiwala, Shweta R.] Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiol, Boston, MA 02215 USA. RP Huffman, JC (reprint author), Massachusetts Gen Hosp, Blake 11,55 Fruit St, Boston, MA 02114 USA. EM jhuffman@partners.org FU National Heart, Lung, and Blood Institute of the National Institutes of Health [R01HL113272]; Expanding the Science and Practice of Gratitude Project; UC Davis; John Templeton Foundation [15627] FX This work was supported by the Expanding the Science and Practice of Gratitude Project run by UC Berkeley's Greater Good Science Center in partnership with UC Davis with funding from the John Templeton Foundation (grant ID: 15627, awarded to JH). Analysis and manuscript preparation time was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number R01HL113272 to JH. The content is solely the responsibility of the authors and does not represent the official views of the funders. NR 107 TC 4 Z9 4 U1 1 U2 3 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 SEP PY 2015 VL 44 BP 11 EP 19 DI 10.1016/j.cct.2015.07.002 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA CT2FB UT WOS:000362616300002 PM 26166171 ER PT J AU Hofmann, SG Curtiss, J Khalsa, SBS Hoge, E Rosenfield, D Bui, E Keshaviah, A Simon, N AF Hofmann, Stefan G. Curtiss, Joshua Khalsa, Sat Bir S. Hoge, Elizabeth Rosenfield, David Bui, Eric Keshaviah, Aparna Simon, Naomi TI Yoga for generalized anxiety disorder: design of a randomized controlled clinical trial SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Clinical trial; Generalized anxiety disorder; Kundalini yoga; Altemadve medicine; Cognitive behavioral therapy; Mindfulness ID PSYCHOMETRIC PROPERTIES; PSYCHOTHERAPY-RESEARCH; PERCEIVED STRESS; MENTAL-DISORDERS; MINDFULNESS; QUESTIONNAIRE; INTERVENTION; METAANALYSIS; VALIDITY; SAMPLE AB Generalized anxiety disorder (GAD) is a common disorder associated with significant distress and interference. Although cognitive behavioral therapy (CBT) has been shown to be the most effective form of psychotherapy, few patients receive or have access to this intervention. Yoga therapy offers another promising, yet under-researched, intervention that is gaining increasing popularity in the general public, as an anxiety reduction intervention. The purpose of this innovative clinical trial protocol is to investigate the efficacy of a Kundalini Yoga intervention, relative to CBT and a control condition. Kundalini yoga and CBT are compared with each other in a noninferiority test and both treatments are compared to stress education training, an attention control intervention, in superiority tests. The sample will consist of 230 individuals with a primary DSM-5 diagnosis of GAD. This randomized controlled trial will compare yoga (N = 95) to both CBT for GAD (N = 95) and stress education (N = 40), a commonly used control condition. All three treatments will be administered by two instructors in a group format over 12 weekly sessions with four to six patients per group. Groups will be randomized using permuted block randomization, which will be stratified by site. Treatment outcome will be evaluated bi-weekly and at 6 month follow-up. Furthermore, potential mediators of treatment outcome will be investigated. Given the individual and economic burden associated with GAD, identifying accessible alternative behavioral treatments will have substantive public health implications. (C) 2015 Elsevier Inc. All rights reserved. C1 [Hofmann, Stefan G.; Curtiss, Joshua] Boston Univ, Boston, MA 02215 USA. [Khalsa, Sat Bir S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Cambridge, MA 02138 USA. [Hoge, Elizabeth; Bui, Eric; Keshaviah, Aparna; Simon, Naomi] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rosenfield, David] So Methodist Univ, Dallas, TX 75275 USA. RP Hofmann, SG (reprint author), Boston Univ, Boston, MA 02215 USA. RI Bui, Eric/J-8347-2015; Hofmann, Stefan/B-8769-2014 OI Bui, Eric/0000-0002-1413-6473; Hofmann, Stefan/0000-0002-3548-9681 FU NCCIH NIH HHS [R01 AT007257, R01 AT007258] NR 66 TC 0 Z9 0 U1 13 U2 31 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 SEP PY 2015 VL 44 BP 70 EP 76 DI 10.1016/j.cct.2015.08.003 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA CT2FB UT WOS:000362616300011 PM 26255236 ER PT J AU Ahn, MJ Tsai, CM Yang, JCH Shepherd, FA Satouchi, M Kim, DW Bazhenova, L Hirashima, T Rukazenkov, Y Cantarini, M Mann, H Ramalingam, SS Mitsudomi, T Janne, PA Goss, GD AF Ahn, M. J. Tsai, C. M. Yang, J. C. H. Shepherd, F. A. Satouchi, M. Kim, D. W. Bazhenova, L. Hirashima, T. Rukazenkov, Y. Cantarini, M. Mann, H. Ramalingam, S. S. Mitsudomi, T. Jaenne, P. A. Goss, G. D. TI AZD9291 activity in patients with EGFR-mutant advanced non-small cell lung cancer (NSCLC) and brain metastases: Data from Phase II studies SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Ahn, M. J.] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Med, Seoul, South Korea. [Tsai, C. M.] Taipei Vet Gen Hosp, Dept Chest Med, Taipei, Taiwan. [Yang, J. C. H.] Natl Taiwan Univ Hosp, Dept Oncol, Taipei, Taiwan. [Shepherd, F. A.] Princess Margaret Canc Ctr, Med Oncol & Hematol, Toronto, ON, Canada. [Satouchi, M.] Hyogo Canc Ctr, Dept Thorac Oncol, Akashi, Hyogo, Japan. [Kim, D. W.] Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. [Bazhenova, L.] UCSD Moores Canc Ctr, Dept Med, San Diego, CA USA. [Hirashima, T.] Osaka Prefectural Ctr Resp & Allerg Dis, Dept Thorac Malignancy, Osaka, Japan. [Rukazenkov, Y.; Cantarini, M.] AstraZeneca, Global Med Dev, Macclesfield, Cheshire, England. [Mann, H.] AstraZeneca, Biometr & Informat Sci, Macclesfield, Cheshire, England. [Ramalingam, S. S.] Emory Univ, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA. [Mitsudomi, T.] Kinki Univ, Fac Med, Dept Thorac Surg, Osaka, Japan. [Jaenne, P. A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Goss, G. D.] Ottawa Hosp, Ctr Canc, Div Med Oncol, Ottawa, ON, Canada. NR 0 TC 14 Z9 14 U1 1 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 3083 BP S625 EP S626 PG 2 WC Oncology SC Oncology GA CS2GP UT WOS:000361887403041 ER PT J AU Ali, S Choueiri, T Wang, K Khaira, D Johnson, A Squillace, R Elvin, J Chmielecki, J Yelensky, R Lipson, D Miller, V Ross, J Stein, M Pal, S Stephens, P AF Ali, S. Choueiri, T. Wang, K. Khaira, D. Johnson, A. Squillace, R. Elvin, J. Chmielecki, J. Yelensky, R. Lipson, D. Miller, V. Ross, J. Stein, M. Pal, S. Stephens, P. TI Comprehensive genomic profiling (CGP) identifies unique and abundant clinically relevant genomic alterations in rare histologies of renal cell carcinoma SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Ali, S.; Wang, K.; Khaira, D.; Johnson, A.; Squillace, R.; Elvin, J.; Chmielecki, J.; Yelensky, R.; Lipson, D.; Miller, V.; Ross, J.; Stephens, P.] Fdn Med Inc, Res & Dev, Cambridge, MA USA. [Choueiri, T.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Ross, J.] Albany Med Ctr, Pathol & Lab Med, Albany, NY USA. [Stein, M.] Rutgers Canc Inst New Jersey, Med Oncol, New Brunswick, NJ USA. [Pal, S.] City Hope Comprehens Canc Ctr, Med Oncol & Expt Therapeut, Duarte, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 2651 BP S530 EP S530 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887402353 ER PT J AU Angelergues, A Bellmunt, J Efstathiou, E Gonzalez, I Gyftaki, R Delanoy, N Ozguroglu, M Flechon, A Guillot, A Le Moulec, S Castellano, D Esteban, E Munarriz, J Balea, BC Ardavanis, A Stefanou, D Oudard, S AF Angelergues, A. Bellmunt, J. Efstathiou, E. Gonzalez, I. Gyftaki, R. Delanoy, N. Ozguroglu, M. Flechon, A. Guillot, A. Le Moulec, S. Castellano, D. Esteban, E. Munarriz, J. Campos Balea, B. Ardavanis, A. Stefanou, D. Oudard, S. TI Response to cabazitaxel in patients with metastatic castration-resistant prostate cancer (mCRPC) poorly responding to docetaxel SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Angelergues, A.; Delanoy, N.; Oudard, S.] Georges Pompidou European Hosp, Clin Oncol, Paris, France. [Bellmunt, J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Clin Oncol, Boston, MA 02115 USA. [Efstathiou, E.; Gyftaki, R.] Alexandra Gen Hosp Athens, Dept Oncol, Athens, Greece. [Gonzalez, I.] Univ Hosp Mar IMIM, Clin Oncol, Barcelona, Spain. [Ozguroglu, M.] Istanbul Univ Cerrahpasa, Clin Oncol, Istanbul, Turkey. [Flechon, A.] Ctr Leon Berard, Cliin Oncol, F-69373 Lyon, France. [Guillot, A.] Inst Cancerol Loire, Clin Oncol, St Etienne, France. [Le Moulec, S.] Val de Grace Hosp, Clin Oncol, Paris, France. [Castellano, D.] Hosp Univ 12 Octubre, Clin Oncol, Madrid, Spain. [Esteban, E.] Hosp Univ Cent Asturias, Clin Oncol, Oviedo, Spain. [Munarriz, J.] Hosp Prov Castellon, Clin Oncol, Castellon de La Plana, Spain. [Campos Balea, B.] Hosp Univ Lucus Augusti, Clin Oncol, Lugo, Spain. [Ardavanis, A.; Stefanou, D.] St Savvas Anticancer Hosp, Clin Oncol, Athens, Greece. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 2538 BP S488 EP S488 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887402241 ER PT J AU Attard, G Gurney, H Loriot, Y Borre, M Andresen, C Wu, K Taylor, C Amelsberg, A Taplin, ME AF Attard, G. Gurney, H. Loriot, Y. Borre, M. Andresen, C. Wu, K. Taylor, C. Amelsberg, A. Taplin, M. E. TI Preliminary findings from PLATO: A two-period, phase 4, randomized, double-blind, placebo-controlled study of continued enzalutamide treatment beyond progression in men with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Attard, G.] Inst Canc Res, Drug Dev Unit, London SW3 6JB, England. [Gurney, H.] Westmead Hosp, Med Oncol, Westmead, NSW 2145, Australia. [Loriot, Y.] Inst Gustave Roussy, Dept Canc Med, Villejuif, France. [Borre, M.] Aarhus Univ Hosp, Dept Clin Epidemiol, Skejby, Denmark. [Andresen, C.] Medivation Inc, Clin Dev, San Francisco, CA USA. [Wu, K.] Medivation Inc, Biostat, San Francisco, CA USA. [Taylor, C.] Astellas Pharma Global, Med Affairs, Kingston Upon Thames, Surrey, England. [Amelsberg, A.] Astellas Pharma, Med Affairs Oncol, Northbrook, IL USA. [Taplin, M. E.] Dana Farber Canc Inst, Clin Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 2537 BP S487 EP S487 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887402240 ER PT J AU Banerjee, S Ledermann, J Matulonis, U Molife, LR Friedlander, M Fielding, A Robertson, JD Spencer, S McMurtry, E Kaye, S AF Banerjee, S. Ledermann, J. Matulonis, U. Molife, L. R. Friedlander, M. Fielding, A. Robertson, J. D. Spencer, S. McMurtry, E. Kaye, S. TI Management of nausea and vomiting during treatment with the capsule (CAP) and tablet (TAB) formulations of the PARP inhibitor olaparib SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Banerjee, S.; Molife, L. R.; Kaye, S.] Royal Marsden Hosp, Drug Dev Unit, Sutton, Surrey, England. [Ledermann, J.] UCL, Inst Canc, London, England. [Matulonis, U.] Dana Farber Canc Inst, Gynecol Canc Ctr, Boston, MA 02115 USA. [Friedlander, M.] Prince Wales Hosp, Dept Clin Oncol, Sydney, NSW, Australia. [Fielding, A.; Robertson, J. D.; McMurtry, E.] AstraZeneca, Global Med Dev, Macclesfield, Cheshire, England. [Spencer, S.] AstraZeneca, Dept Stat, Macclesfield, Cheshire, England. NR 0 TC 1 Z9 1 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 2759 BP S550 EP S550 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887402412 ER PT J AU Bang, YJ Doi, T De Braud, F Piha-Paul, S Hollebecque, A Razak, ARA Lin, CC Ott, PA He, AR Yuan, SS Koshiji, M Lam, B Aggarwal, R AF Bang, Y. J. Doi, T. De Braud, F. Piha-Paul, S. Hollebecque, A. Razak, A. R. Abdul Lin, C. C. Ott, P. A. He, A. R. Yuan, S. S. Koshiji, M. Lam, B. Aggarwal, R. TI Safety and efficacy of pembrolizumab (MK-3475) in patients (pts) with advanced biliary tract cancer: Interim results of KEYNOTE-028 SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Bang, Y. J.] Seoul Natl Univ Hosp, Internal Med, Seoul 110744, South Korea. [Doi, T.] Natl Canc Ctr Hosp East, Expt Therapeut, Chiba, Japan. [De Braud, F.] Fdn IRCCS Ist Nazl Tumori, Oncol, Milan, Italy. [Piha-Paul, S.] Univ Texas MD Anderson Canc Ctr, Invest Canc Therapeut, Houston, TX 77030 USA. [Hollebecque, A.] Gustave Roussy, Therapeut Innovat, Villejuif, France. [Razak, A. R. Abdul] Princess Margaret Canc Ctr, Med Oncol, Toronto, ON, Canada. [Lin, C. C.] Natl Taiwan Univ Hosp, Oncol, Taipei, Taiwan. [Ott, P. A.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [He, A. R.] Georgetown Univ, Med Oncol, Washington, DC USA. [Yuan, S. S.] Merck & Co Inc, BARDS, Kenilworth, NJ USA. [Koshiji, M.; Lam, B.] Merck & Co Inc, Clin Oncol, Kenilworth, NJ USA. [Aggarwal, R.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. NR 0 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 525 BP S112 EP S112 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887400335 ER PT J AU Bardia, A Cameron, JS Venkatesan, K Robinson, D Porter, D Kim, SB Parton, M Kummel, S Estevez, LG Huang, CS Castan, JC Ruiz-Borrego, M Telli, M Martorell, PM Lopez, R Beck, JT Ismail-Khan, R Chen, SC Hurvitz, S Mayer, I AF Bardia, A. Cameron, J. S. Venkatesan, K. Robinson, D. Porter, D. Kim, S. B. Parton, M. Kuemmel, S. Estevez, L. G. Huang, C. S. Cortes Castan, J. Ruiz-Borrego, M. Telli, M. Martin Martorell, P. Lopez, R. Beck, J. T. Ismail-Khan, R. Chen, S. C. Hurvitz, S. Mayer, I. TI Synergy of LCL161, an antagonist of inhibitor of apoptosis proteins (IAPs), with paclitaxel in a gene expression signature-enriched cohort of triple-negative breast cancer (TNBC) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Bardia, A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Cameron, J. S.; Venkatesan, K.; Robinson, D.; Porter, D.] Novartis Inst BioMed Res, Oncol Translat Med, Cambridge, MA USA. [Kim, S. B.] Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea. [Parton, M.] Royal Marsden Hosp, Breast Unit, London SW3 6JJ, England. [Kuemmel, S.] KEM, Breast Unit, Essen, Germany. [Estevez, L. G.] Ctr Integral Oncol Clara Campal, Breast Unit, Madrid, Spain. [Huang, C. S.] Natl Taiwan Univ Hosp, Breast Ctr, Taipei, Taiwan. [Cortes Castan, J.] Vall dHebron Univ Hosp, Dept Oncol, Barcelona, Spain. [Ruiz-Borrego, M.] Hosp Univ Vigen Del Rocio, Dept Med Oncol, Seville, Spain. [Telli, M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Martin Martorell, P.] Hosp Clin Univ, Med Oncol, Valencia, Spain. [Lopez, R.] Hosp Clin Univ Santiago de Compostela, Med Oncol, Santiago De Compostela, Spain. [Beck, J. T.] Highlands Oncol Grp, Med Oncol, Fayetteville, AR USA. [Ismail-Khan, R.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Med, Tampa, FL 33682 USA. [Chen, S. C.] Chang Gung Univ, Coll Med, Chang Gung Mem Hosp, Taoyuan, Taiwan. [Hurvitz, S.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Dept Med Hematol Oncol, Los Angeles, CA 90024 USA. [Mayer, I.] Vanderbilt Ingram Canc Ctr, Dept Hematol Oncol, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 1977 BP S326 EP S326 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887401346 ER PT J AU Besse, B Johnson, M Janne, PA Garassino, M Eberhardt, WEE Peters, S Toh, CK Kurata, T Li, Z Kowanetz, M Mocci, S Sandler, A Rizvi, NA AF Besse, B. Johnson, M. Jaenne, P. A. Garassino, M. Eberhardt, W. E. E. Peters, S. Toh, C. K. Kurata, T. Li, Z. Kowanetz, M. Mocci, S. Sandler, A. Rizvi, N. A. TI Phase II, single-arm trial (BIRCH) of atezolizumab as first-line or subsequent therapy for locally advanced or metastatic PD-L1-selected non-small cell lung cancer (NSCLC) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Besse, B.] Gustave Roussy, Villejuif, France. [Besse, B.] Univ Paris 11, Orsay, France. [Johnson, M.] Sarah Cannon Res Inst, Nashville, TN USA. [Jaenne, P. A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Garassino, M.] Fdn IRCCS Ist Nazl Tumori, Thorac Oncol Unit, Milan, Italy. [Eberhardt, W. E. E.] Univ Klinikum Essen, West German Canc Ctr, Essen, Germany. [Eberhardt, W. E. E.] Ruhrlandklin, Essen, Germany. [Peters, S.] CHU Vaudois, Dept Oncol, Lausanne, Switzerland. [Toh, C. K.] Natl Canc Ctr, Singapore, Singapore. [Kurata, T.] Kansai Med Univ, Hirakata Hosp, Osaka, Japan. [Li, Z.; Kowanetz, M.; Mocci, S.; Sandler, A.] Genentech Inc, San Francisco, CA 94080 USA. [Rizvi, N. A.] Columbia Univ, New York, NY USA. NR 0 TC 8 Z9 8 U1 4 U2 15 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 16LBA BP S717 EP S718 PG 2 WC Oncology SC Oncology GA CS2GP UT WOS:000361887403267 ER PT J AU Brastianos, P Carter, S Santagata, S Cahill, D Taylor-Weiner, A Jones, R Ligon, K Tabernero, J Seoane, J Saez, EM Johnson, B Choueiri, T Stemmer-Rachamimov, A Lin, N Beroukhim, R Batchelor, T Baselga, J Louis, D Hahn, W Getz, G AF Brastianos, P. Carter, S. Santagata, S. Cahill, D. Taylor-Weiner, A. Jones, R. Ligon, K. Tabernero, J. Seoane, J. Martinez Saez, E. Johnson, B. Choueiri, T. Stemmer-Rachamimov, A. Lin, N. Beroukhim, R. Batchelor, T. Baselga, J. Louis, D. Hahn, W. Getz, G. TI Genomic characterization of brain metastases and paired primary tumors reveals branched evolution and potential therapeutic targets SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Brastianos, P.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Carter, S.; Taylor-Weiner, A.] Broad Inst Harvard & MIT, Canc Program, Cambridge, MA USA. [Santagata, S.] Brigham & Womens Hosp, Pathol, Boston, MA 02115 USA. [Cahill, D.] Massachusetts Gen Hosp, Ctr Canc, Neurosurg, Boston, MA USA. [Jones, R.; Johnson, B.; Choueiri, T.; Lin, N.; Beroukhim, R.; Hahn, W.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Ligon, K.] Dana Farber Canc Inst, Pathol, Boston, MA 02115 USA. [Tabernero, J.; Seoane, J.] Vall Hebron Univ Hosp, Med Oncol, Barcelona, Spain. [Martinez Saez, E.] Vall Hebron Univ Hosp, Pathol, Barcelona, Spain. [Stemmer-Rachamimov, A.; Louis, D.; Getz, G.] Massachusetts Gen Hosp, Pathol, Boston, MA 02114 USA. [Batchelor, T.] Massachusetts Gen Hosp, Neurol, Boston, MA 02114 USA. [Baselga, J.] Mem Sloan Kettering Canc Ctr, Oncol, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 2905 BP S586 EP S586 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887402511 ER PT J AU Brenner, A Cohen, Y Vredenburgh, J Peters, K Nayak, L Blumenthal, D Bokstein, F Breitbart, E Bangio, L Sher, N Harats, D Wen, P AF Brenner, A. Cohen, Y. Vredenburgh, J. Peters, K. Nayak, L. Blumenthal, D. Bokstein, F. Breitbart, E. Bangio, L. Sher, N. Harats, D. Wen, P. TI Phase 2 study of VB-111, an anti-cancer gene therapy, as monotherapy followed by combination of VB-111 with bevacizumab, in patients with recurrent glioblastoma SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Brenner, A.] Univ Texas Hlth Sci Ctr San Antonio, Inst Drug Dev, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. [Cohen, Y.; Breitbart, E.; Bangio, L.; Sher, N.; Harats, D.] VBL Therapeut, Or Yehuda, Israel. [Vredenburgh, J.] St Francis Hosp & Med Ctr, Hartford, CT USA. [Peters, K.] Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr, Durham, NC USA. [Nayak, L.; Wen, P.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. [Blumenthal, D.; Bokstein, F.] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Div Neurooncol, IL-69978 Tel Aviv, Israel. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 2901 BP S584 EP S584 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887402507 ER PT J AU Calvo, E Lopez-Martin, JA Bendell, J Eder, JP Taylor, M Ott, PA Pietanza, MC Horn, L Jager, D De Braud, F Morse, MA Ascierto, PA Le, DT Amin, A Evans, J Simon, J Lin, CS Christensen, O Antonia, SJ AF Calvo, E. Lopez-Martin, J. A. Bendell, J. Eder, J. P. Taylor, M. Ott, P. A. Pietanza, M. C. Horn, L. Jaeger, D. De Braud, F. Morse, M. A. Ascierto, P. A. Le, D. T. Amin, A. Evans, J. Simon, J. Lin, C. S. Christensen, O. Antonia, S. J. TI Nivolumab (NIVO) monotherapy or in combination with ipilimumab (IPI) for treatment of recurrent small cell lung cancer (SCLC) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Calvo, E.] START Madrid, Ctr Integral Oncol Clara Campa, Madrid, Spain. [Lopez-Martin, J. A.] Hosp Univ 12 Octubre, Serv Oncol Med, Madrid, Spain. [Bendell, J.] Tennessee Oncol PLLC, Sarah Cannon Res Inst, Drug Dev Unit, Nashville, TN USA. [Eder, J. P.] Yale Canc Ctr, Dev Therapeut, New Haven, CT USA. [Taylor, M.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Ott, P. A.] Dana Farber Canc Inst, Ctr Immunooncol, Boston, MA 02115 USA. [Pietanza, M. C.] Mem Sloan Kettering Canc Ctr, Dept Med, Div Solid Tumor Oncol, Thorac Oncol Serv, New York, NY 10021 USA. [Horn, L.] Vanderbilt Ingram Canc Ctr, Dept Med, Nashville, TN USA. [Jaeger, D.] Univ Heidelberg Hosp, Natl Ctr Tumor Dis, Heidelberg, Germany. [De Braud, F.] Ist Nazl Tumori, Med Oncol, I-20133 Milan, Italy. [Morse, M. A.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Ascierto, P. A.] Ist Nazl Tumori, Unit Med Oncol & Innovat Therapy, Fdn Pascale, Naples, Italy. [Le, D. T.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Oncol Gastrointestinal Canc, Baltimore, MD USA. [Amin, A.] Carolinas HealthCare Syst, Levine Canc Inst, Charlotte, NC USA. [Evans, J.] Beatson West Scotland Canc Ctr, Translat Canc Therapeut, Glasgow, Lanark, Scotland. [Simon, J.] Bristol Myers Squibb Co, Immunooncol Biomarkers, Princeton, NJ USA. [Lin, C. S.] Bristol Myers Squibb Co, Biostat, Princeton, NJ USA. [Christensen, O.] Bristol Myers Squibb Co, Clin Res Oncol, Princeton, NJ USA. [Antonia, S. J.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Thorac Oncol, Tampa, FL 33612 USA. NR 0 TC 3 Z9 3 U1 2 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 3098 BP S633 EP S633 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887403056 ER PT J AU Camidge, DR Bazhenova, LA Salgia, R Langer, CJ Gold, K Rosell, R Shaw, AT Weiss, GJ Dorer, DJ Rivera, VM Conlan, MG Kerstein, D Gettinger, SN AF Camidge, D. R. Bazhenova, L. A. Salgia, R. Langer, C. J. Gold, K. Rosell, R. Shaw, A. T. Weiss, G. J. Dorer, D. J. Rivera, V. M. Conlan, M. G. Kerstein, D. Gettinger, S. N. TI Assessment of Brigatinib (AP26113) CNS Activity in Patients (Pts) With ALK plus NSCLC and intracranial metastases in a Phase 1/2 Study SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Camidge, D. R.] Univ Colorado, Ctr Canc, Sch Med, Div Med Oncol, Aurora, CO USA. [Bazhenova, L. A.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Salgia, R.] Univ Chicago Med, Chest Oncol & Thorac Oncol Res Program, Chicago, IL USA. [Langer, C. J.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Gold, K.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Rosell, R.] Dexeus Univ Inst, Catalan Inst Oncol Badalona, Barcelona, Spain. [Shaw, A. T.] Massachusetts Gen Hosp, Dept Med, Hematol Oncol, Boston, MA 02114 USA. [Weiss, G. J.] Canc Treatment Ctr Amer, Western Reg Med Ctr, Goodyear, AZ USA. [Dorer, D. J.; Rivera, V. M.; Conlan, M. G.; Kerstein, D.] ARIAD Pharmaceut Inc, Oncol, Cambridge, MA USA. [Gettinger, S. N.] Yale Canc Ctr, Thorac Oncol, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 3 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 3061 BP S616 EP S616 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887403020 ER PT J AU Chen, YW Chang, AY Chen, CH Chiu, HY Chiu, YH Feng, YC Lin, SH Sheu, YH Jhang, AH Wu, CP Lin, YF AF Chen, Y. W. Chang, A. Y. Chen, C. H. Chiu, H. Y. Chiu, Y. H. Feng, Y. C. Lin, S. H. Sheu, Y. H. Jhang, A. H. Wu, C. P. Lin, Y. F. TI Impact of race and ethnicity on stage at diagnosis of non-small cell lung cancer (NSCLC) and receipt of treatment in contemporary United States population: A SEER-based analysis SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Chen, Y. W.; Feng, Y. C.; Lin, S. H.; Sheu, Y. H.; Lin, Y. F.] Harvard Univ, THC Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Chang, A. Y.] Harvard Univ, THC Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. [Chen, C. H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Chiu, H. Y.] Taipei Med Univ Hosp, Dept Surg, Taipei, Taiwan. [Chiu, Y. H.] Harvard Univ, THC Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Jhang, A. H.] Landseed Hosp, Dept Community Med, Taoyuan, Taiwan. [Wu, C. P.] Albert Einstein Coll Med, Jacobi Med Ctr, Dept Med, Bronx, NY 10467 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 1036 BP S157 EP S157 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887400478 ER PT J AU Chen, YW Chang, AY Chen, CH Chiu, HYC Chiu, YH Feng, YC Lin, SH Sheu, YH Jhang, AH Wu, CP Lin, YF AF Chen, Y. W. Chang, A. Y. Chen, C. H. Chiu, H. Y. C. Chiu, Y. H. Feng, Y. C. Lin, S. H. Sheu, Y. H. Jhang, A. H. Wu, C. P. Lin, Y. F. TI Heterogeneous presentation of patients diagnosed with T1 non-small cell lung cancer (NSCLC) across race and ethnicity in contemporary United States population SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Chen, Y. W.; Feng, Y. C.; Lin, S. H.; Sheu, Y. H.; Lin, Y. F.] Harvard Univ, Dept Epidemiol, THC Sch Publ Hlth, Boston, MA 02115 USA. [Chang, A. Y.] Harvard Univ, Dept Global Hlth & Populat, THC Sch Publ Hlth, Boston, MA 02115 USA. [Chen, C. H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Chiu, H. Y. C.] Taipei Med Univ Hosp, Dept Surg, Taipei, Taiwan. [Chiu, Y. H.] Harvard Univ, THC Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Jhang, A. H.] Landseed Hosp, Dept Community Med, Taoyuan, Taiwan. [Wu, C. P.] Albert Einstein Coll Med, Jacobi Med Ctr, Dept Med, Bronx, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 1035 BP S156 EP S157 PG 2 WC Oncology SC Oncology GA CS2GP UT WOS:000361887400477 ER PT J AU Choueiri, T Escudier, B Powles, T Mainwaring, P Rini, B Donskov, F Hammers, H Hutson, T Roth, B Peltola, K Lee, JL Heng, D Schmidinger, M Borgman-Hagey, A Hessel, C Scheffold, C Schwab, G Tannir, N Motzer, R AF Choueiri, T. Escudier, B. Powles, T. Mainwaring, P. Rini, B. Donskov, F. Hammers, H. Hutson, T. Roth, B. Peltola, K. Lee, J. L. Heng, D. Schmidinger, M. Borgman-Hagey, A. Hessel, C. Scheffold, C. Schwab, G. Tannir, N. Motzer, R. TI Cabozantinib versus everolimus in patients with advanced renal cell carcinoma: Results of the randomized phase 3 METEOR trial SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Choueiri, T.] Dana Farber Canc Inst, Lank Ctr Genitourinary Onc, Boston, MA 02115 USA. [Escudier, B.] Inst Gustave Roussy, Dept Med Oncol, Villejuif, France. [Powles, T.] Barts Canc Inst, Genitourinary Oncol, London, England. [Mainwaring, P.] ICON Canc Care, Mater Med Ctr, South Brisbane, Qld, Australia. [Rini, B.] Cleveland Clin, Taussig Canc Inst, Hematol & Oncol, Cleveland, OH 44106 USA. [Donskov, F.] Aarhus Univ Hosp, Dept Oncol, DK-8000 Aarhus, Denmark. [Hammers, H.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Hutson, T.] Baylor Charles A Sammons Canc Ctr, Texas Oncol, Dallas, TX USA. [Roth, B.] Washington Univ, Sch Med, Med Oncol, St Louis, MO USA. [Peltola, K.] Helsinki Univ Cent Hosp, Dept Oncol, Helsinki, Finland. [Lee, J. L.] Univ Ulsan, Asan Med Ctr, Coll Med, Seoul, South Korea. [Heng, D.] Tom Baker Canc Clin, Dept Med Oncol, Calgary, AB, Canada. [Schmidinger, M.] Med Univ Vienna, Div Clin Oncol, Vienna, Austria. [Borgman-Hagey, A.; Scheffold, C.; Schwab, G.] Exelixis, Clin Dev, San Francisco, CA USA. [Hessel, C.] Exelixis, Biostat, San Francisco, CA USA. [Tannir, N.] Univ Texas MD Anderson Canc Ctr, Dept Gu Med Oncol, Houston, TX 77030 USA. [Motzer, R.] Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 4LBA BP S708 EP S709 PG 2 WC Oncology SC Oncology GA CS2GP UT WOS:000361887403250 ER PT J AU Chow, L Mehra, R Haddad, R Gupta, S Weiss, J Berger, R Burtness, B Tahara, M Keam, B Le, D Cheng, J Heath, K Pathiraja, K Seiwert, T AF Chow, L. Mehra, R. Haddad, R. Gupta, S. Weiss, J. Berger, R. Burtness, B. Tahara, M. Keam, B. Le, D. Cheng, J. Heath, K. Pathiraja, K. Seiwert, T. TI Antitumor activity of the Anti-PD-1 antibody pembrolizumab in subgroups of patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC): Exploratory analyses from KEYNOTE-012 SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Chow, L.] Univ Washington, Med Oncol, Seattle, WA 98195 USA. [Mehra, R.] Fox Chase Canc Ctr, Med Oncol, Philadelphia, PA 19111 USA. [Haddad, R.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Gupta, S.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Expt Therapeut, Tampa, FL 33612 USA. [Weiss, J.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Div Hematol & Oncol, Chapel Hill, NC 27599 USA. [Berger, R.] Chaim Sheba Med Ctr, Oncol, IL-52621 Tel Hashomer, Israel. [Burtness, B.] Yale Univ, Sch Med, Internal Med, New Haven, CT USA. [Tahara, M.] Natl Canc Ctr Hosp East, Head & Neck Med Oncol, Kashiwa, Chiba, Japan. [Keam, B.] Seoul Natl Univ Hosp, Internal Med, Seoul 110744, South Korea. [Le, D.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Oncol, Baltimore, MD USA. [Cheng, J.] Merck & Co Inc, Clin Oncol, Kenilworth, NJ USA. [Heath, K.] Merck & Co Inc, Oncol, Kenilworth, NJ USA. [Pathiraja, K.] Merck & Co Inc, BARDS, Kenilworth, NJ USA. [Seiwert, T.] Univ Chicago, Med, Sect Hematol Oncol, Chicago, IL 60637 USA. NR 0 TC 1 Z9 1 U1 4 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 2866 BP S579 EP S579 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887402492 ER PT J AU Currow, D Temel, J Fearon, K Friend, J Yan, Y Abernethy, A AF Currow, D. Temel, J. Fearon, K. Friend, J. Yan, Y. Abernethy, A. TI ROMANA 3: A safety extension study of anamorelin in advanced non-small cell lung cancer (NSCLC) patients with cachexia SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Currow, D.] Flinders Univ S Australia, Palliat Serv, Adelaide, SA 5001, Australia. [Currow, D.] Flinders Univ S Australia, Support Serv, Adelaide, SA 5001, Australia. [Temel, J.] Massachusetts Gen Hosp, Dept Oncol, Boston, MA 02114 USA. [Fearon, K.] Western Gen Hosp, Colorectal Unit, Edinburgh EH4 2XU, Midlothian, Scotland. [Friend, J.; Yan, Y.] Helsinn Therapeut US Inc, Res & Dev, Iselin, NJ USA. [Abernethy, A.] Duke Univ, Dept Med, Durham, NC 27706 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 1603 BP S239 EP S239 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887401097 ER PT J AU Demetri, G Patel, SR Thomas, S Livingston, M Undevia, SD Richardson, G Singh, AS Seth, R Forscher, C Hinshaw, I Hussein, A D'Amato, G Chawla, S Khokhar, NZ Park, YC Knoblauch, RE Parekh, TV Maki, RG Von Mehren, M AF Demetri, G. Patel, S. R. Thomas, S. Livingston, M. Undevia, S. D. Richardson, G. Singh, A. S. Seth, R. Forscher, C. Hinshaw, I. Hussein, A. D'Amato, G. Chawla, S. Khokhar, N. Z. Park, Y. C. Knoblauch, R. E. Parekh, T. V. Maki, R. G. Von Mehren, M. TI Efficacy and safety of trabectedin (T) or dacarbazine (D) for treatment of patients (pts) with advanced leiomyosarcoma (LMS) or liposarcoma (LPS) after prior chemotherapy SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Demetri, G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Expt Therapeut, Boston, MA 02115 USA. [Patel, S. R.] Univ Texas MD Anderson Canc Ctr, Dept Sarcoma Med Oncol, Houston, TX 77030 USA. [Thomas, S.] Univ Texas MD Anderson Canc Ctr, Oncol, Orlando, FL USA. [Livingston, M.] Blumenthal Canc Ctr, Med Oncol, Charlotte, NC USA. [Undevia, S. D.] Edwards Canc Ctr, Oncol, Naperville, IL USA. [Richardson, G.] Cabrini Hosp, Oncol, Malvern, Vic, Australia. [Singh, A. S.] UCLA Med Ctr, Oncol, Santa Monica, CA USA. [Seth, R.] SUNY Upstate Med Univ, Med Oncol, Syracuse, NY 13210 USA. [Forscher, C.] Cedars Sinai Med Ctr, Oncol, Los Angeles, CA 90048 USA. [Hinshaw, I.] Rocky Mt Canc Ctr, Oncol, Denver, CO USA. [Hussein, A.] Mem Canc Inst, Oncol, Hollywood, FL USA. [D'Amato, G.] Georgia Canc Associates, Hematol Oncol, Atlanta, GA USA. [Chawla, S.] Sarcoma Oncol Ctr, Oncol, Santa Monica, CA USA. [Khokhar, N. Z.; Knoblauch, R. E.; Parekh, T. V.] Janssen Res & Dev LLC, Clin Oncol, Raritan, NJ USA. [Park, Y. C.] Janssen Res & Dev LLC, Clin Biostat, Raritan, NJ USA. [Maki, R. G.] Mt Sinai Sch Med, Hematol Oncol, New York, NY USA. [Von Mehren, M.] Fox Chase Canc Ctr, Med Oncol, Philadelphia, PA 19111 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 3436 BP S700 EP S700 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887403231 ER PT J AU Falcone, A Garcia-Carbonero, R Tabernero, J Sobrero, A Peeters, M Zaniboni, A Hochster, H Lenz, HJ Tran, B Yamaguchi, K Muro, K Denda, T Tsuji, Y Wahba, M Benedetti, F Ohtsu, A Mayer, RJ Van Cutsem, E AF Falcone, A. Garcia-Carbonero, R. Tabernero, J. Sobrero, A. Peeters, M. Zaniboni, A. Hochster, H. Lenz, H. J. Tran, B. Yamaguchi, K. Muro, K. Denda, T. Tsuji, Y. Wahba, M. Benedetti, F. Ohtsu, A. Mayer, R. J. Van Cutsem, E. TI Low rates of hospitalizations with TAS-102 in the European (EU) subregion of the Phase 3 RECOURSE trial in patients (pts) with metastatic colorectal cancer (mCRC) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Falcone, A.] Univ Pisa, AO Pisana Osped S Chiara, Dept Translat Res & New Technol Med, Pisa, Italy. [Garcia-Carbonero, R.] Hosp Univ Virgen del Rocio, Inst Biomed Sevilla, Seville, Spain. [Tabernero, J.] Vall dHebron Univ Hosp, Med Oncol Serv, Barcelona, Spain. [Sobrero, A.] IRCCS AOU San Martino IST, Dipartmentio Oncol Med, Genoa, Italy. [Peeters, M.] Univ Antwerp Hosp, Dept Oncol, Edegem, Belgium. [Zaniboni, A.] Fdn Poliambulanza, Oncol Med, Brescia, Italy. [Hochster, H.] Yale Canc Ctr, Gastrointestinal Canc Program, New Haven, CT USA. [Lenz, H. J.] USC Norris Comprehens Canc Ctr, Gastrointestinal Canc Program, Los Angeles, CA USA. [Tran, B.] Royal Melbourne Hosp, Med Oncol, Melbourne, Vic, Australia. [Yamaguchi, K.] Saitama Canc Ctr, Dept Gastroenterol, Saitama, Japan. [Muro, K.] Aichi Canc Ctr Hosp, Dept Clin Oncol, Nagoya, Aichi, Japan. [Denda, T.] Chiba Canc Ctr, Div Gastroenterol, Chiba 2608717, Japan. [Tsuji, Y.] Tonan Hosp, KKR Sapporo Med Ctr, Sapporo, Hokkaido, Japan. [Wahba, M.] Taiho Oncol Inc, Med Affairs & Med Pharmacovigilance, Princeton, NJ USA. [Benedetti, F.] Taiho Oncol Inc, Oncol, Princeton, NJ USA. [Ohtsu, A.] Natl Canc Ctr Hosp East, Dept GI Oncol, Kashiwa, Chiba, Japan. [Mayer, R. J.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Van Cutsem, E.] Univ Hosp Gasthuisberg, Gastroenterol Digest Oncol, Leuven, Belgium. NR 0 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 2150 BP S383 EP S383 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887401496 ER PT J AU Ferreira, A Palha, A Correia, L Filipe, P Rodrigues, V Costa, L Miranda, A Andre, R Fernandes, J Gouveia, J Coelho, JLP Moreira, A Brito, M Ribeiro, J Metzger, O Lin, NU Vaz-Luiz, I AF Ferreira, A. Palha, A. Correia, L. Filipe, P. Rodrigues, V. Costa, L. Miranda, A. Andre, R. Fernandes, J. Gouveia, J. Passos Coelho, J. L. Moreira, A. Brito, M. Ribeiro, J. Metzger-Filho, O. Lin, N. U. Vaz-Luiz, I. TI Patterns of care and relative effectiveness of aromatase inhibitors compared to tamoxifen in patients with early breast cancer: A multi-institutional study SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Ferreira, A.] Hosp Santa Maria, Inst Med Mol, Dana Farber Canc Inst, Med Oncol, Lisbon, Portugal. [Palha, A.; Correia, L.] Hosp Santa Maria, Dept Pathol, Lisbon, Portugal. [Filipe, P.] Hosp Santa Maria, Med Oncol, Lisbon, Portugal. [Rodrigues, V.] Hosp Santa Maria, Dept Pharm, Lisbon, Portugal. [Costa, L.] Hosp Santa Maria, Inst Med Mol, Med Oncol, Lisbon, Portugal. [Miranda, A.; Andre, R.] Registo Oncol Reg Sul, Lisbon, Portugal. [Fernandes, J.; Gouveia, J.] Hosp CUF Lisboa Descobertas & Infante Santo, Med Oncol, Lisbon, Portugal. [Passos Coelho, J. L.] Hosp Luz, Med Oncol, Lisbon, Portugal. [Moreira, A.; Brito, M.] Inst Portugues Oncol Lisboa FG, Med Oncol, Lisbon, Portugal. [Ribeiro, J.] Fundacao Champalimaud, Med Oncol, Lisbon, Portugal. [Metzger-Filho, O.; Lin, N. U.; Vaz-Luiz, I.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 1965 BP S322 EP S322 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887401334 ER PT J AU Gadgeel, S Soria, JC Goldman, JW Wakelee, H Camidge, DR Yu, H Varga, A Solomon, B Oxnard, GR Ou, SH Papadimitrakopoulou, V Liu, SV Reckamp, K Spira, A Piotrowska, Z Despain, D Karlovich, C Yurasov, S Sequist, LV AF Gadgeel, S. Soria, J. C. Goldman, J. W. Wakelee, H. Camidge, D. R. Yu, H. Varga, A. Solomon, B. Oxnard, G. R. Ou, S. H. Papadimitrakopoulou, V. Liu, S. V. Reckamp, K. Spira, A. Piotrowska, Z. Despain, D. Karlovich, C. Yurasov, S. Sequist, L. V. TI Efficacy of rociletinib (co-1686) in EGFR-mutant non-small cell lung cancer (NSCLC) patients (pts) assessed with a plasma EGFR test SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Gadgeel, S.] Karmanos Canc Ctr, Clin Arrangements, Detroit, MI USA. [Soria, J. C.] Gustave Roussy Canc Ctr, Drug Dev, Villejuif, France. [Goldman, J. W.] UCLA Med Ctr, Med Hematol & Oncol, Santa Monica, CA USA. [Wakelee, H.] Stanford Univ, Med Ctr, Thorac Oncol, Stanford, CA 94305 USA. [Camidge, D. R.] Univ Colorado, Thorac Oncol, Denver, CO 80202 USA. [Yu, H.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Varga, A.] Gustave Roussy Canc Ctr, Dept Med, Villejuif, France. [Solomon, B.] Peter MacCallum Canc Ctr, Mol Therapeut & Biomarkers, Melbourne, Vic, Australia. [Oxnard, G. R.] Dana Farber Canc Inst, Thorac Oncol, Boston, MA 02115 USA. [Ou, S. H.] Univ Calif Irvine, Hematol Oncol, Orange, CA USA. [Papadimitrakopoulou, V.] Univ Texas MD Anderson Canc Ctr, Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. [Liu, S. V.] Georgetown Univ, Med Ctr, Lombardi Comprehens Care Ctr, Washington, DC 20007 USA. [Reckamp, K.] City Hope Comprehens Canc Ctr, Lung Canc & Thorac Oncol, Duarte, CA USA. [Spira, A.] Virginia Canc Specialists, Med Oncol, Fairfax, VA USA. [Piotrowska, Z.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Despain, D.] Clovis Oncol, Biostat, Boulder, CO USA. [Karlovich, C.] Clovis Oncol, Mol Diagnost, San Francisco, CA USA. [Yurasov, S.] Clovis Oncol, Clin Dev, San Francisco, CA USA. [Sequist, L. V.] Massachusetts Gen Hosp, Med Oncol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 5 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 3088 BP S628 EP S628 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887403046 ER PT J AU Giaccone, G Camidge, DR Liu, SV Powderly, J Hodi, FS Gettinger, SN Heist, RS Liu, B Wallin, J Funke, R Waterkamp, D Ready, NE AF Giaccone, G. Camidge, D. R. Liu, S. V. Powderly, J. Hodi, F. S. Gettinger, S. N. Heist, R. S. Liu, B. Wallin, J. Funke, R. Waterkamp, D. Ready, N. E. TI Safety, activity and biomarkers of atezolizumab (MPDL3280A) with platinum-based chemotherapy (chemo) in non-small cell lung cancer (NSCLC): A Phase Ib study SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Giaccone, G.; Liu, S. V.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Camidge, D. R.] Univ Colorado, Denver, CO 80202 USA. [Powderly, J.] Carolina BioOncol Inst, Huntersville, NC USA. [Hodi, F. S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gettinger, S. N.] Yale Canc Ctr, New Haven, CT USA. [Heist, R. S.; Ready, N. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Liu, B.; Wallin, J.; Funke, R.; Waterkamp, D.] Genentech Inc, San Francisco, CA 94080 USA. NR 0 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 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 513 BP S107 EP S108 PG 2 WC Oncology SC Oncology GA CS2GP UT WOS:000361887400323 ER PT J AU Glen, H Hsieh, J Michaelson, MD Kim, HJ Sachdev, P Kadowaki, T Funahashi, Y Larkin, J Motzer, R AF Glen, H. Hsieh, J. Michaelson, M. D. Kim, H. J. Sachdev, P. Kadowaki, T. Funahashi, Y. Larkin, J. Motzer, R. TI Correlative analyses of serum biomarkers and clinical outcomes in the phase 2 study of lenvatinib, everolimus, and the combination, in patients with metastatic renal cell carcinoma following 1 VEGF-targeted therapy SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Glen, H.] Beatson West Scotland Canc Ctr, Glasgow, Lanark, Scotland. [Hsieh, J.; Motzer, R.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Michaelson, M. D.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Kim, H. J.; Sachdev, P.] Eisai Inc, Woodcliff Lake, NJ USA. [Kadowaki, T.] Eisai & Co Ltd, Tsukuba, Ibaraki, Japan. [Funahashi, Y.] Eisai Inc, Andover, MA USA. [Larkin, J.] Royal Marsden NHS Hosp, London, England. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 432 BP S89 EP S89 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887400273 ER PT J AU Goss, GD Yang, JCH Ahn, MJ Tsai, CM Bazhenova, L Sequist, LV Ramalingam, SS Shepherd, FA Ghiorghiu, S Cantarini, M Mann, H Mitsudomi, T Janne, PA AF Goss, G. D. Yang, J. C. H. Ahn, M. J. Tsai, C. M. Bazhenova, L. Sequist, L. V. Ramalingam, S. S. Shepherd, F. A. Ghiorghiu, S. Cantarini, M. Mann, H. Mitsudomi, T. Jaenne, P. A. TI AZD9291 in pre-treated patients with T790M positive advanced non-small cell lung cancer (NSCLC): Pooled analysis from two Phase II studies SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Goss, G. D.] Ottawa Hosp, Ctr Canc, Div Med Oncol, Ottawa, ON, Canada. [Yang, J. C. H.] Natl Taiwan Univ Hosp, Dept Oncol, Taipei, Taiwan. [Ahn, M. J.] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Med, Seoul, South Korea. [Tsai, C. M.] Taipei Vet Gen Hosp, Dept Chest Med, Taipei, Taiwan. [Bazhenova, L.] UCSD Moores Canc Ctr, Dept Med, San Diego, CA USA. [Sequist, L. V.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Ramalingam, S. S.] Emory Univ, Dept Hematol & Med Oncol, Winship Canc Inst, Atlanta, GA 30322 USA. [Shepherd, F. A.] Princess Margaret Canc Ctr, Med Oncol & Hematol, Toronto, ON, Canada. [Ghiorghiu, S.] AstraZeneca, Global Med Dev, Cambridge, England. [Cantarini, M.] AstraZeneca, Global Med Dev, Macclesfield, Cheshire, England. [Mann, H.] AstraZeneca, Biometr & Informat Sci, Macclesfield, Cheshire, England. [Mitsudomi, T.] Kinki Univ, Fac Med, Dept Thorac Surg, Osaka, Japan. [Jaenne, P. A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 3113 BP S640 EP S640 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887403071 ER PT J AU Guo, M Sherman, S Wirth, L Schlumberger, M Dutcus, C Robinson, B Tahara, M Latimer, N AF Guo, M. Sherman, S. Wirth, L. Schlumberger, M. Dutcus, C. Robinson, B. Tahara, M. Latimer, N. TI Overall survival gain with lenvatinib vs. placebo in radioactive iodine refractory differentiated thyroid cancer (RR-DTC): An updated analysis SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Guo, M.; Dutcus, C.] Eisai Inc, Woodcliff Lake, NJ USA. [Sherman, S.] Univ Texas MD Anderson Canc Ctr, Dept Endocrine Neoplasia & Hormonal Disorders, Houston, TX 77030 USA. [Wirth, L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Schlumberger, M.] Gustave Roussy, Dept Nucl Med & Endocrine Oncol, Villejuif, France. [Schlumberger, M.] Univ Paris 11, Villejuif, France. [Robinson, B.] Univ Sydney, Kolling Inst Med Res, Sydney, NSW 2006, Australia. [Tahara, M.] Natl Canc Ctr Hosp East, Dept Head & Neck, Kashiwa, Chiba, Japan. [Latimer, N.] Univ Sheffield, ScHARR, Sheffield, S Yorkshire, England. NR 0 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 2805 BP S559 EP S559 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887402437 ER PT J AU Happold, C Gorlia, T Chinot, O Gilbert, M Nabors, LB Wick, W Pugh, SL Hegi, M Cloughesy, T Roth, P Reardon, DA Perry, JR Mehta, MP Stupp, R Weller, M AF Happold, C. Gorlia, T. Chinot, O. Gilbert, M. Nabors, L. B. Wick, W. Pugh, S. L. Hegi, M. Cloughesy, T. Roth, P. Reardon, D. A. Perry, J. R. Mehta, M. P. Stupp, R. Weller, M. TI Does valproic acid improve survival in glioblastoma? A meta-analysis of randomized trials in newly diagnosed glioblastoma SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Happold, C.; Roth, P.; Weller, M.] Univ Zurich Hosp, Neurol, CH-8091 Zurich, Switzerland. [Gorlia, T.] EORTC, Ctr Data, Brussels, Belgium. [Chinot, O.] Aix Marseille Univ, Univ Hosp Timone, Assistance Publ Hop Marseille, Div Neurooncol, Marseille, France. [Gilbert, M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Nabors, L. B.] Univ Alabama Birmingham, Neurooncol, Birmingham, AL USA. [Wick, W.] Heidelberg Univ, Heidelberg, Germany. [Wick, W.] German Canc Res Ctr, Neurol Clin, Heidelberg, Germany. [Pugh, S. L.] Stat & Data Management Ctr, NRG Oncol, Philadelphia, PA USA. [Hegi, M.] Univ Lausanne Hosp, Dept Clin Neurosci, Lausanne, Switzerland. [Cloughesy, T.] Univ Calif Los Angeles, Neurooncol Program, Los Angeles, CA USA. [Reardon, D. A.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. [Perry, J. R.] Univ Toronto, Div Neurol, Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada. [Mehta, M. P.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Stupp, R.] Univ Zurich Hosp, Oncol, CH-8091 Zurich, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 26LBA BP S723 EP S723 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887403277 ER PT J AU Harshman, L Werner, L Wong, YN Yu, E Alva, A Crabb, S Powles, T Rosenberg, J Baniel, J Vaishampayan, U Berthold, D Ladoire, S Hussain, S Milowsky, M Agarwal, N Necchi, A Pal, S Recine, F Bellmunt, J Galsky, M AF Harshman, L. Werner, L. Wong, Y. N. Yu, E. Alva, A. Crabb, S. Powles, T. Rosenberg, J. Baniel, J. Vaishampayan, U. Berthold, D. Ladoire, S. Hussain, S. Milowsky, M. Agarwal, N. Necchi, A. Pal, S. Recine, F. Bellmunt, J. Galsky, M. TI Patterns and potential benefit of adjuvant chemotherapy for residual muscle invasive disease after neoadjuvant chemotherapy for muscle invasive urothelial cancer (MIUC) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Harshman, L.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Werner, L.] Dana Farber Canc Inst, Biostat, Boston, MA 02115 USA. [Wong, Y. N.] Fox Chase Canc Ctr, Med Oncol, Philadelphia, PA 19111 USA. [Yu, E.] Univ Washington, Med Oncol, Seattle, WA 98195 USA. [Alva, A.] Univ Michigan, Med Oncol, Ann Arbor, MI 48109 USA. [Crabb, S.] Univ Southampton, Med Oncol, Southampton, Hants, England. [Powles, T.] Barts & London NHS Trust, Med Oncol, London, England. [Rosenberg, J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Baniel, J.] Rabin Med Ctr, Med Oncol, Petah Tivka, Israel. [Vaishampayan, U.] Karmanos Canc Inst, Med Oncol, Detroit, MI USA. [Berthold, D.] CHU Vaudois, Med Oncol, Lausanne, Switzerland. [Ladoire, S.] Georges Francois Leclerc Canc Ctr, Med Oncol, Dijon, France. [Hussain, S.] Univ Liverpool, Clatterbridge Canc Ctr, Med Oncol, Liverpool L69 3BX, Merseyside, England. [Milowsky, M.] Univ N Carolina, Med Oncol, Chapel Hill, NC USA. [Agarwal, N.] Univ Utah, Huntsman Canc Inst, Med Oncol, Salt Lake City, UT USA. [Necchi, A.] Fdn IRCCS Ist Nazl Tumori, Med Oncol, Milan, Italy. [Pal, S.] City Hope Comprehens Canc Ctr, Med Oncol, Los Angeles, CA USA. [Recine, F.] San Camillo Forlanini Hosp, Med Oncol, Rome, Italy. [Bellmunt, J.] Hosp Mar, Boston, MA USA. [Bellmunt, J.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Galsky, M.] Mt Sinai Med Ctr, Med Oncol, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 2619 BP S518 EP S518 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887402322 ER PT J AU Hodi, FS Gibney, G Sullivan, R Sosman, JA Slingluff, CL Lawrence, DP Logan, TF Schuchter, LM Nair, S Fecher, L Buchbinder, E Ruisi, M Kong, G Horak, C Weber, JS AF Hodi, F. S. Gibney, G. Sullivan, R. Sosman, J. A. Slingluff, C. L., Jr. Lawrence, D. P. Logan, T. F. Schuchter, L. M. Nair, S. Fecher, L. Buchbinder, E. Ruisi, M. Kong, G. Horak, C. Weber, J. S. TI An open-label, randomized, phase 2 study of nivolumab (NIVO) given sequentially with ipilimumab (IPI) in patients with advanced melanoma (CheckMate 064) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Hodi, F. S.; Buchbinder, E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gibney, G.] Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. [Sullivan, R.; Lawrence, D. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sosman, J. A.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Slingluff, C. L., Jr.] Univ Virginia, Sch Med, Charlottesville, VA USA. [Logan, T. F.] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. [Schuchter, L. M.] Univ Penn, Philadelphia, PA 19104 USA. [Nair, S.] Lehigh Valley Hlth Network, Allentown, PA USA. [Fecher, L.] Univ Michigan, Ann Arbor, MI 48109 USA. [Ruisi, M.; Horak, C.] Bristol Myers Squibb Co, Princeton, NJ USA. [Kong, G.] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. [Weber, J. S.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. NR 0 TC 5 Z9 6 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 23LBA BP S721 EP S721 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887403274 ER PT J AU Hurley, J Hu, L Brock, G Sinclair, I Sullivan, R O'Neill, V Skog, J Flaherty, K AF Hurley, J. Hu, L. Brock, G. Sinclair, I. Sullivan, R. O'Neill, V. Skog, J. Flaherty, K. TI Profiling exosomal mRNAs in patients undergoing immunotherapy for malignant melanoma SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Hurley, J.; Hu, L.; Brock, G.; O'Neill, V.; Skog, J.] Exosome Diagnost, R&D, Cambridge, MA USA. [Sinclair, I.] Exosome Diagnost, Clin Lab, St Paul, MN USA. [Sullivan, R.; Flaherty, K.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 452 BP S96 EP S96 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887400293 ER PT J AU Jeffers, M Beckmann, G Reischl, J Rutstein, M Wagner, A Demetri, GD Teufel, M AF Jeffers, M. Beckmann, G. Reischl, J. Rutstein, M. Wagner, A. Demetri, G. D. Teufel, M. TI Tumor genotyping and clonal evolution in KIT during regorafenib treatment in the phase III GRID study of regorafenib vs placebo in tyrosine kinase inhibitor (TKI)-refractory GIST SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Jeffers, M.] Bayer HealthCare Pharmaceut, Clin Sci Expt Med Oncol, Whippany, NJ USA. [Beckmann, G.] Bayer Pharma AG, Global Drug Discovery Bioinformat, Berlin, Germany. [Reischl, J.] Bayer Pharma AG, Global Drug Discovery Biomarker Strategy Dev, Berlin, Germany. [Rutstein, M.] Bayer HealthCare Pharmaceut, Global Clin Dev Oncol, Whippany, NJ USA. [Wagner, A.] Bayer Pharma AG, Global Clin Dev, Berlin, Germany. [Demetri, G. D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Demetri, G. D.] Harvard Univ, Sch Med, Ludwig Ctr, Boston, MA USA. [Teufel, M.] Bayer HealthCare Pharmaceut, Global Drug Discovery Biomarker Strategy Dev, Whippany, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 2341 BP S448 EP S448 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887402138 ER PT J AU Juric, D Rodon, J Bauer, TM Wainberg, Z Tolaney, S Modi, S Martin, AG Hengelage, T Melendez, M Choudhury, S Nauwelaerts, H Bedard, PL AF Juric, D. Rodon, J. Bauer, T. M. Wainberg, Z. Tolaney, S. Modi, S. Gonzalez Martin, A. Hengelage, T. Melendez, M. Choudhury, S. Nauwelaerts, H. Bedard, P. L. TI A Phase Ib/II study of alpelisib (BYL719) and ganitumab (AMG 479) in adult patients with selected advanced solid tumors SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Juric, D.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Rodon, J.] Hosp Valle De Hebron, Med Oncol, Barcelona, Spain. [Bauer, T. M.] Sarah Cannon Res Inst, Nashville, TN USA. [Bauer, T. M.] Tennessee Oncol PLLC, Hematol Oncol, Nashville, TN USA. [Wainberg, Z.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Tolaney, S.] Dana Farber Canc Inst, Med, Boston, MA 02115 USA. [Modi, S.] Mem Sloan Kettering Canc Ctr, Breast Canc Med, New York, NY 10021 USA. [Gonzalez Martin, A.] MD Anderson Canc Ctr Madrid, Med Oncol, Madrid, Spain. [Hengelage, T.; Nauwelaerts, H.] Novartis Pharma AG, Oncol Global Dev, Basel, Switzerland. [Melendez, M.] Novartis Pharma AG, Biostat, Basel, Switzerland. [Choudhury, S.] Novartis Pharmaceut, Oncol Clin Pharmacol, E Hanover, NJ USA. [Bedard, P. L.] Princess Margaret Canc Ctr, Med Oncol, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 342 BP S68 EP S68 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887400211 ER PT J AU Kulke, MH Horsch, D Caplin, M Anthony, L Bergsland, E Oberg, K Welin, S Warner, R Lombard-Bohas, C Kunz, P Grande, E Valle, J Fleming, D Lapuerta, P Banks, P Jackson, S Wheeler, D Zambrowicz, B Sands, A Pavel, M AF Kulke, M. H. Hoersch, D. Caplin, M. Anthony, L. Bergsland, E. Oberg, K. Welin, S. Warner, R. Lombard-Bohas, C. Kunz, P. Grande, E. Valle, J. Fleming, D. Lapuerta, P. Banks, P. Jackson, S. Wheeler, D. Zambrowicz, B. Sands, A. Pavel, M. TI Telotristat etiprate is effective in treating patients with carcinoid syndrome that is inadequately controlled by somatostatin analog therapy (the phase 3 TELESTAR clinical trial) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Kulke, M. H.] Dana Farber Canc Inst, Gastrointestinal Canc Ctr, Boston, MA 02115 USA. [Hoersch, D.] Zent Klin Bad Berka, Ctr Neuroendocrine Tumors, Bad Berka, Germany. [Caplin, M.] Royal Free Hosp, Ctr Gastroenterol, London NW3 2QG, England. [Anthony, L.] Univ Kentucky, Med Ctr, Dept Med, Div Med Oncol, Lexington, KY 40536 USA. [Bergsland, E.] Univ Calif San Francisco, Med Ctr, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Oberg, K.; Welin, S.] Uppsala Univ, Dept Med Sci Endocrine Oncol, Uppsala, Sweden. [Warner, R.] Mt Sinai Hosp, Dept Med Gastroenterol, New York, NY 10029 USA. [Lombard-Bohas, C.] Hosp Civils Lyon, Hop Edouard Herriot, Med Oncol, Lyon, France. [Kunz, P.] Stanford Univ, Sch Med Med Oncol, Palo Alto, CA 94304 USA. [Grande, E.] Hosp Univ Ramon y Cajal, Dept Med Oncol, Madrid, Spain. [Valle, J.] Christie NHS Fdn Trust, Med Oncol, London, England. [Fleming, D.] Ipsen BioSci, Clin Dev, Cambridge, MA USA. [Lapuerta, P.; Banks, P.; Jackson, S.] Lexicon Pharmaceut Inc, Clin Dev, The Woodlands, TX USA. [Wheeler, D.] Lexicon Pharmaceut Inc, Med Affairs, The Woodlands, TX USA. [Zambrowicz, B.; Sands, A.] Lexicon Pharmaceut Inc, Res & Dev, The Woodlands, TX USA. [Pavel, M.] Charite, Dept Gastroenterol & Hepatol, D-13353 Berlin, Germany. NR 0 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 37LBA BP S728 EP S728 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887403288 ER PT J AU Lambertini, M Ceppi, M Poggio, F Peccatori, FA Azim, HA Ugolini, D Pronzato, P Loibl, S Moore, HCF Partridge, AH Del Mastro, L AF Lambertini, M. Ceppi, M. Poggio, F. Peccatori, F. A. Azim, H. A. Ugolini, D. Pronzato, P. Loibl, S. Moore, H. C. F. Partridge, A. H. Del Mastro, L. TI Ovarian suppression with luteinizing hormone-releasing hormone agonists during chemotherapy as a strategy to preserve ovarian function and fertility in breast cancer patients: A systematic review and meta-analysis of randomized studies SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Lambertini, M.; Poggio, F.; Pronzato, P.] IRCCS AOU San Martino IST, Dept Med Oncol, UO Oncol Med 2, Genoa, Italy. [Ceppi, M.] IRCCS AOU San Martino IST, Dept Epidemiol, Genoa, Italy. [Peccatori, F. A.] European Inst Oncol, Dept Gynecol Oncol, Fertil & Procreat Unit, Milan, Italy. [Azim, H. A.] Univ Libre Bruxelles, Inst Jules Bordet, BrEAST Data Ctr, Dept Med, Brussels, Belgium. [Ugolini, D.] Univ Genoa, IRCCS AOU San Martino IST, Dept Internal Med, Clin Epidemiol Unit, Genoa, Italy. [Loibl, S.] Goethe Univ Frankfurt, German Breast Grp, Neu Isenburg, Germany. [Moore, H. C. F.] Cleveland Clin Fdn, Taussig Canc Inst, Dept Hematol & Oncol, Cleveland, OH 44195 USA. [Partridge, A. H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Breast Oncol Program,Susan F Smith Ctr, Boston, MA 02115 USA. [Del Mastro, L.] IRCCS AOU San Martino IST, Dept Med Oncol, UO Sviluppo Terapie Innovat, Genoa, Italy. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 1957 BP S318 EP S319 PG 2 WC Oncology SC Oncology GA CS2GP UT WOS:000361887401326 ER PT J AU Larkin, J Chiarion-Sileni, V Gonzalez, R Grob, JJ Cowey, CL Lao, CD Wagstaff, J Hogg, D Hill, A Carlino, MS Wolter, P Lebbe, C Schachter, J Thomas, L Hassel, JC Lorigan, P Walker, D Jiang, J Hodi, FS Wolchok, JD AF Larkin, J. Chiarion-Sileni, V. Gonzalez, R. Grob, J. J. Cowey, C. L. Lao, C. D. Wagstaff, J. Hogg, D. Hill, A. Carlino, M. S. Wolter, P. Lebbe, C. Schachter, J. Thomas, L. Hassel, J. C. Lorigan, P. Walker, D. Jiang, J. Hodi, F. S. Wolchok, J. D. TI Efficacy and safety in key patient subgroups of nivolumab (NIVO) alone or combined with ipilimumab (IPI) versus IPI alone in treatment-naive patients with advanced melanoma (MEL) (CheckMate 067) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Larkin, J.] Royal Marsden Hosp, London SW3 6JJ, England. [Chiarion-Sileni, V.] IOV IRCCS Melanoma Oncol Unit, Melanoma Canc Unit, Padua, Italy. [Gonzalez, R.] Univ Colorado, Ctr Canc, Div Med Oncol, Aurora, CO USA. [Grob, J. J.] Aix Marseille Univ, Hop La Timone, APHM, Dept Dermatol & Skin Canc, Marseille, France. [Cowey, C. L.] Baylor Charles Sammons Canc Ctr, Hematol Med Oncol, Dallas, TX USA. [Lao, C. D.] Univ Michigan, Med Oncol, Ann Arbor, MI 48109 USA. [Wagstaff, J.] South Wales Wales Canc Inst Singleton Hosp, Oncol Clin Trials Unit, Swansea, W Glam, Wales. [Hogg, D.] Univ Toronto, Princess Margaret Hosp, Clin Studies Resource Ctr, Toronto, ON, Canada. [Hill, A.] Tasman Oncol Res, Dept Hlth, South Gold Coast, Qld, Australia. [Carlino, M. S.] Melanoma Inst Australia, Sydney, NSW, Australia. [Carlino, M. S.] Univ Sydney, Med Oncol, Sydney, NSW 2006, Australia. [Wolter, P.] UZ Leuven, Med Oncol, Leuven, Belgium. [Lebbe, C.] Univ Paris Diderot, Hop St Luis, Dept Dermatol, Paris, France. [Schachter, J.] Chaim Sheba Med Ctr, Ella Inst Treatment & Res Melanoma & Skin Canc, Inst Oncol, IL-52621 Tel Hashomer, Israel. [Thomas, L.] Ctr Hosp Lyon Sud, Dept Dermatol, F-69310 Pierre Benite, France. [Hassel, J. C.] Univ Hosp, German Canc Res Ctr, Dept Dermatol, Heidelberg, Germany. [Hassel, J. C.] Natl Ctr Tumor Dis, Heidelberg, Germany. [Lorigan, P.] Christie NHS Fdn Trust, Med Oncol, Manchester, Lancs, England. [Walker, D.] Bristol Myers Squibb Co, Global Clin Res, Princeton, NJ USA. [Jiang, J.] Bristol Myers Squibb Co, Global Biometr Sci, Hopewell, NJ USA. [Hodi, F. S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Wolchok, J. D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Wolchok, J. D.] Weill Cornell Med Coll, Melanoma Serv, New York, NY USA. [Wolchok, J. D.] Weill Cornell Med Coll, Immunotherapeut Serv, New York, NY USA. NR 0 TC 3 Z9 3 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 3303 BP S664 EP S665 PG 2 WC Oncology SC Oncology GA CS2GP UT WOS:000361887403141 ER PT J AU Long, GV Dummer, R Ribas, A Puzanov, I Michielin, O Vanderwalde, A Andtbacka, RHI Cebon, J Fernandez, E Malvehy, J Olszanski, AJ Gajewski, TF Kirkwood, JM Gause, C Chen, L Kaufman, DR Chou, J Hodi, FS AF Long, G. V. Dummer, R. Ribas, A. Puzanov, I. Michielin, O. Vanderwalde, A. Andtbacka, R. H. I. Cebon, J. Fernandez, E. Malvehy, J. Olszanski, A. J. Gajewski, T. F. Kirkwood, J. M. Gause, C. Chen, L. Kaufman, D. R. Chou, J. Hodi, F. S. TI Safety data from the phase 1b part of the MASTERKEY-265 study combining talimogene laherparepvec (T-VEC) and pembrolizumab for unresectable stage IIIB-IV melanoma SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Long, G. V.] Univ Sydney, Melanoma Inst Australia, Sydney, NSW 2006, Australia. [Long, G. V.] Mater Hosp, Melanoma, Sydney, NSW, Australia. [Dummer, R.] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. [Ribas, A.] Univ Calif Los Angeles, Med Ctr, Dept Hematol & Oncol, Los Angeles, CA 90024 USA. [Puzanov, I.] Vanderbilt Univ, Med Ctr, Div Hematol & Oncol, Nashville, TN USA. [Michielin, O.] CHU Vaudois, Dept Oncol, Lausanne, Switzerland. [Vanderwalde, A.] West Clin, Dept Hematol & Oncol, Memphis, TN USA. [Andtbacka, R. H. I.] Univ Utah, Huntsman Canc Inst, Div Surg Oncol, Salt Lake City, UT USA. [Cebon, J.] Olivia Newton John Canc Ctr, Med Oncol, Heidelberg, Vic, Australia. [Fernandez, E.] Hop Cantonal Univ Geneva, Ctr Oncol, Geneva, Switzerland. [Malvehy, J.] Hosp Clin Barcelona, Dept Dermatol, Barcelona, Spain. [Olszanski, A. J.] Fox Chase Canc Ctr, Dept Hematol Oncol, Philadelphia, PA 19111 USA. [Gajewski, T. F.] Univ Chicago Med, Dept Hematol Oncol, Chicago, IL USA. [Kirkwood, J. M.] Univ Pittsburgh, Dept Med, Inst Canc, Pittsburgh, PA USA. [Gause, C.] Merck & Co Inc, Biostat, Kenilworth, NJ USA. [Chen, L.] Amgen Inc, Biostat, Thousand Oaks, CA 91320 USA. [Kaufman, D. R.] Merck & Co Inc, Med, Kenilworth, NJ USA. [Chou, J.] Amgen Inc, Med, Thousand Oaks, CA 91320 USA. [Hodi, F. S.] Dana Farber Canc Inst, Melanoma Ctr, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 3 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 24LBA BP S722 EP S722 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887403275 ER PT J AU Montgomery, B Joshua, A Gleave, M Fleshner, N Bubley, G True, L Tretiakova, M Wu, K Novotny, W Peterson, A Amelsberg, A Taplin, ME AF Montgomery, B. Joshua, A. Gleave, M. Fleshner, N. Bubley, G. True, L. Tretiakova, M. Wu, K. Novotny, W. Peterson, A. Amelsberg, A. Taplin, M. E. TI A randomized, open-label, phase 2 study of enzalutamide as neoadjuvant therapy for patients undergoing prostatectomy for localized prostate cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress 2015 / 18th Meeting of the European-Cancer-Organization (ECCO) / 40th Meeting of the European-Society-for-Medical-Oncology (ESMO) CY SEP 25-29, 2015 CL Vienna, AUSTRIA SP European Canc Org, European Soc Med Oncol C1 [Montgomery, B.] Univ Washington, Genitourinary Med oncol, Seattle, WA 98195 USA. [Joshua, A.] Princess Margaret Canc Ctr, Dept Med Oncol, Toronto, ON, Canada. [Gleave, M.] Vancouver Prostate Ctr, Dept Urol Sci, Vancouver, BC, Canada. [Fleshner, N.] Princess Margaret Canc Ctr, Urol, Toronto, ON, Canada. [Bubley, G.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [True, L.; Tretiakova, M.] Univ Washington, Med Ctr, Pathol, Seattle, WA 98195 USA. [Wu, K.] Medivation Inc, Biostat, San Francisco, CA USA. [Novotny, W.; Peterson, A.] Medivation Inc, Clin Dev, San Francisco, CA USA. [Amelsberg, A.] Astellas Pharma Global Dev, Global Med Affairs, Northbrook, IL USA. [Taplin, M. E.] Dana Farber Canc Inst, Genitourinary Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 2501 BP S473 EP S473 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887402205 ER PT J AU Newbold, K Sherman, S Wirth, LJ Habra, MA Rietschel, P Song, J Schlumberger, M Gianoukakis, A AF Newbold, K. Sherman, S. Wirth, L. J. Habra, M. A. Rietschel, P. Song, J. Schlumberger, M. Gianoukakis, A. TI The influence of time to objective response on lenvatinib clinical outcomes in the phase 3 SELECT trial SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Newbold, K.] Royal Marsden Natl Hlth Serv Trust, Oncol, London, England. [Sherman, S.; Habra, M. A.] Univ Texas MD Anderson Canc Ctr, Dept Endocrine Neoplasia & Hormonal Disorders, Div Internal Med, Houston, TX 77030 USA. [Wirth, L. J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Rietschel, P.; Song, J.] Eisai Inc, Woodcliff Lake, NJ USA. [Schlumberger, M.] Gustave Roussy, Dept Nucl Med & Endocrine Oncol, Villejuif, France. [Schlumberger, M.] Univ Paris 11, Villejuif, France. [Gianoukakis, A.] Harbor UCLA Med Ctr, Div Endocrinol & Metab, Torrance, CA 90509 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 2862 BP S577 EP S577 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887402488 ER PT J AU Ott, PA Piha-Paul, SA Munster, P Pishvaian, MJ Van Brummelen, E Cohen, R Gomez-Roca, C Ejadi, S Stein, M Chan, E Simonelli, M Morosky, A Yuan, SS Koshiji, M Bennouna, J AF Ott, P. A. Piha-Paul, S. A. Munster, P. Pishvaian, M. J. Van Brummelen, E. Cohen, R. Gomez-Roca, C. Ejadi, S. Stein, M. Chan, E. Simonelli, M. Morosky, A. Yuan, S. S. Koshiji, M. Bennouna, J. TI Pembrolizumab (MK-3475) for PD-L1-positive squamous cell carcinoma (SCC) of the anal canal: Preliminary safety and efficacy results from KEYNOTE-028 SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Ott, P. A.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Piha-Paul, S. A.] Univ Texas MD Anderson Canc Ctr, Invest Canc Therapeut, Houston, TX 77030 USA. [Munster, P.] UCSF Helen Diller Family Comprehens Canc Ctr, Med Hematol Oncol, San Francisco, CA USA. [Pishvaian, M. J.] Georgetown Univ, Hematol Oncol, Washington, DC USA. [Van Brummelen, E.] Netherlands Canc Inst, Clin Pharmacol, Amsterdam, Netherlands. [Cohen, R.] Univ Penn, Perelman Sch Med, Hematol Oncol, Philadelphia, PA 19104 USA. [Gomez-Roca, C.] Inst Claudius Regaud, Clin Res Unit, Toulouse, France. [Ejadi, S.] Virgina G Piper Canc Ctr, Clin Trials, Scottsdale, AZ USA. [Stein, M.] Rutgers Canc Inst New Jersey, Med Oncol, New Brunswick, NJ USA. [Chan, E.] Vanderbilt Ingram Canc Ctr, Hematol Oncol, Nashville, TN USA. [Simonelli, M.] Humanitas Canc Ctr, Oncol & Hematol, Rozzano, Italy. [Morosky, A.] Merck & Co Inc, CDEO Clin Dev Execut Org, Kenilworth, NJ USA. [Yuan, S. S.] Merck & Co Inc, BARDS, Kenilworth, NJ USA. [Koshiji, M.] Merck & Co Inc, Clin Oncol, Kenilworth, NJ USA. [Bennouna, J.] Inst Cancerol Ouest, Med Oncol, Nantes, France. NR 0 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 500 BP S102 EP S102 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887400310 ER PT J AU Oudard, S Angelergues, A Efstathiou, E Gonzalez, I Gyftaki, R Delanoy, N Ozguroglu, M Flechon, A Guillot, A Le Moulec, S Castellano, D Esteban, E Munarriz, J Balea, BC Ardavanis, A Stefanou, D Bellmunt, J AF Oudard, S. Angelergues, A. Efstathiou, E. Gonzalez, I. Gyftaki, R. Delanoy, N. Ozguroglu, M. Flechon, A. Guillot, A. Le Moulec, S. Castellano, D. Esteban, E. Munarriz, J. Campos Balea, B. Ardavanis, A. Stefanou, D. Bellmunt, J. TI Updated results of the FLAC European database of metastatic castration resistant prostate cancer (mCRPC) patients (pts) treated with life extending therapies in post-docetaxel (D) setting SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Oudard, S.; Angelergues, A.; Delanoy, N.] Hop Europeen Georges Pompidou, Med Oncol, Paris, France. [Efstathiou, E.; Gyftaki, R.] Alexandra Gen Hosp Athens, Dept Oncol, Athens, Greece. [Gonzalez, I.] Univ Hosp del Mar IMIM, Clin Oncol, Barcelona, Spain. [Ozguroglu, M.] Istanbul Univ Cerrahpasa, Clin Oncol, Istanbul, Turkey. [Flechon, A.] Ctr Leon Berard, Clin Oncol, F-69373 Lyon, France. [Guillot, A.] Inst Cancerol Loire, Clin Oncol, St Etienne, France. [Le Moulec, S.] Val de Grace Hosp, Clin Oncol, Paris, France. [Castellano, D.] Hosp Univ 12 Octubre, Clin Oncol, Madrid, Spain. [Esteban, E.] Hosp Univ Cent Asturias, Clin Oncol, Oviedo, Spain. [Munarriz, J.] Hosp Prov Castellon, Clin Oncol, Castellon de La Plana, Spain. [Campos Balea, B.] Hosp Univ Lucus Augusti, Clin Oncol, Lugo, Spain. [Ardavanis, A.; Stefanou, D.] St Savvas Anticancer Hosp, Clin Oncol, Athens, Greece. [Bellmunt, J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Clin Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 2541 BP S489 EP S489 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887402244 ER PT J AU Patel, S Von Mehren, M Reed, D Agulnik, M Kaiser, P Charlson, J Kraft, A Hamm, J Karnad, A Ryan, C Rushing, D Meyer, C Khokhar, NZ McCarthy, S Park, YC Knoblauch, RE Parekh, TV Maki, RG Demetri, GD AF Patel, S. Von Mehren, M. Reed, D. Agulnik, M. Kaiser, P. Charlson, J. Kraft, A. Hamm, J. Karnad, A. Ryan, C. Rushing, D. Meyer, C. Khokhar, N. Z. McCarthy, S. Park, Y. C. Knoblauch, R. E. Parekh, T. V. Maki, R. G. Demetri, G. D. TI Final overall survival (OS) analysis of the randomized phase 3 study of trabectedin (T) or dacarbazine (D) for the treatment of patients (pts) with advanced leiomyosarcoma (LMS) or liposarcoma (LPS) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Patel, S.] Univ Texas MD Anderson Canc Ctr, Dept Sarcoma Med Oncol, Houston, TX 77030 USA. [Von Mehren, M.] Fox Chase Canc Ctr, Med Oncol, Philadelphia, PA 19111 USA. [Reed, D.] Univ S Florida, H Lee Moffitt Canc Ctr, Sarcoma Dept, Tampa, FL 33682 USA. [Agulnik, M.] Northwestern Univ, Med Hematol Oncol, Chicago, IL 60611 USA. [Kaiser, P.] Lutheran Gen Adv Care Ctr, Hematol Oncol, Park Ridge, IL USA. [Charlson, J.] Med Coll Wisconsin, Hematol & Oncol, Milwaukee, WI 53226 USA. [Kraft, A.] Med Univ S Carolina, Hematol & Oncol, Charleston, SC 29425 USA. [Hamm, J.] Norton Canc Inst, Med Oncol, Louisville, KY USA. [Karnad, A.] Univ Texas San Antonio, CTRC, Med Oncol & Hematol, San Antonio, TX USA. [Ryan, C.] Oregon Hlth & Sci Univ, Knight Canc Inst, Med Oncol, Portland, OR 97201 USA. [Rushing, D.] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. [Meyer, C.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Med Oncol, Baltimore, MD USA. [Khokhar, N. Z.; McCarthy, S.; Knoblauch, R. E.; Parekh, T. V.] Janssen Res & Dev LLC, Clin Oncol, Raritan, NJ USA. [Park, Y. C.] Janssen Res & Dev LLC, Clin Biostat, Raritan, NJ USA. [Maki, R. G.] Mt Sinai Sch Med, Hematol Oncol, New York, NY USA. [Demetri, G. D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Demetri, G. D.] Ludwig Ctr Harvard, Ctr Sarcoma & Bone Oncol, Boston, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 3403 BP S689 EP S689 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887403199 ER PT J AU Petrylak, D Eigl, B Senkus, E Loriot, Y Twardowski, P Castellano, D Blais, N Sridhar, S Sternberg, C Retz, M Blumenstein, B Jacobs, C Stewart, P Bellmunt, J AF Petrylak, D. Eigl, B. Senkus, E. Loriot, Y. Twardowski, P. Castellano, D. Blais, N. Sridhar, S. Sternberg, C. Retz, M. Blumenstein, B. Jacobs, C. Stewart, P. Bellmunt, J. TI Baseline circulating tumor cells (CTC) and serum heat shock protein 27 (Hsp27) levels are increased in advanced bladder cancer (BC) patients with poor prognostic factors: Results from the randomized phase 2 Borealis-1 (TM) trial of first-line gemcitabine/cisplatin plus apatorsen or placebo SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Petrylak, D.] Yale Canc Ctr, Prostate & Urol Canc Program, New Haven, CT USA. [Eigl, B.] British Columbia Canc Agcy, Vancouver Canc Ctr, Vancouver, BC V5Z 4E6, Canada. [Senkus, E.] Uniwersyteckie Ctr Klin, Klin Onkol & Radioterapii, Gdansk, Poland. [Loriot, Y.] Gustave Roussy Canc Ctr, Dept Canc Med, Villejuif, France. [Twardowski, P.] City Hope Natl Med Ctr, Med Oncol, Duarte, CA 91010 USA. [Castellano, D.; Sridhar, S.] Hosp Univ 12 Octubre, Serv Oncol Med, Madrid, Spain. [Blais, N.] Univ Montreal, Dept Med, CHUM Hop Notre Dame, Montreal, PQ H3C 3J7, Canada. [Sridhar, S.] Princess Margaret Canc Ctr, Med Oncol, Toronto, ON, Canada. [Sternberg, C.] San Camillo & Forlanini Hosp, Dept Med Oncol, Rome, Italy. [Retz, M.] Tech Univ Munich, Urol Klin & Poliklin, D-80290 Munich, Germany. [Blumenstein, B.] Tri Arc Consulting, Washington, DC USA. [Jacobs, C.] OncoGenex Pharmaceut Inc, Clin Res, Bothell, WA USA. [Stewart, P.] OncoGenex Pharmaceut Inc, Clin Dev, Bothell, WA USA. [Bellmunt, J.] Dana Farber Canc Inst, Bladder Canc Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 2637 BP S525 EP S525 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887402339 ER PT J AU Ramos, J Casey, M Bamias, A De Giorgi, U Bellmunt, J Harshman, L Ladoire, S Wong, YN Alva, A Necchi, A Recine, F Vaishampayan, U Niegisch, G Pal, S Crabb, S Golshayan, A Srinivas, S Rosenberg, J Galsky, M Yu, E AF Ramos, J. Casey, M. Bamias, A. De Giorgi, U. Bellmunt, J. Harshman, L. Ladoire, S. Wong, Y. N. Alva, A. Necchi, A. Recine, F. Vaishampayan, U. Niegisch, G. Pal, S. Crabb, S. Golshayan, A. Srinivas, S. Rosenberg, J. Galsky, M. Yu, E. TI Predicting venous thromboembolism (VTE) in metastatic urothelial tract tumors (UTT) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Ramos, J.; Yu, E.] Univ Washington, Med, Seattle, WA 98195 USA. [Casey, M.; Galsky, M.] Mt Sinai Sch Med, Med, New York, NY USA. [Bamias, A.] Univ Athens, Med, Athens, Greece. [De Giorgi, U.] Ist Sci Romagnolo Studio & Cura Tumori, Med, Meldola, Italy. [Bellmunt, J.] Hosp del Mar, Med, Barcelona, Spain. [Harshman, L.] Dana Farber Canc Inst, Med, Boston, MA 02115 USA. [Ladoire, S.] Ctr Georges Francois Leclerc, Med, Dijon, France. [Wong, Y. N.] Fox Chase Canc Ctr, Med, Philadelphia, PA 19111 USA. [Alva, A.] Univ Michigan, Med, Ann Arbor, MI 48109 USA. [Necchi, A.] Ist Nazl Tumori Fdn IRCCS, Med, Milan, Italy. [Recine, F.] San Camillo Forlanini Hosp, Med, Rome, Italy. [Vaishampayan, U.] Karmanos Canc Inst, Med, Detroit, MI USA. [Niegisch, G.] Univ Dusseldorf, Med, Dusseldorf, Germany. [Pal, S.] City Hope Natl Med Ctr, Med, Duarte, CA USA. [Crabb, S.] Univ Southampton, Med, Southampton, Hants, England. [Golshayan, A.] Med Univ S Carolina, Med, Charleston, SC USA. [Srinivas, S.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Rosenberg, J.] Mem Sloan Kettering Canc Ctr, Med, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 2607 BP S514 EP S514 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887402310 ER PT J AU Raut, C Miceli, R Strauss, D Swallow, C Hohenberger, P Van Coevorden, F Rutkowski, P Fiore, M Callegaro, D Casali, P Haas, R Hayes, A Honore, C Cannell, A Jakob, J Szacht, M Fairweather, M Pollock, R Bonvalot, S Gronchi, A AF Raut, C. Miceli, R. Strauss, D. Swallow, C. Hohenberger, P. Van Coevorden, F. Rutkowski, P. Fiore, M. Callegaro, D. Casali, P. Haas, R. Hayes, A. Honore, C. Cannell, A. Jakob, J. Szacht, M. Fairweather, M. Pollock, R. Bonvalot, S. Gronchi, A. TI External validation of a nomogram predicting disease-free (DFS) and overall survival (OS) in patients (pts) with primary retroperitoneal sarcoma (pRPS) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Raut, C.; Fairweather, M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Raut, C.; Fairweather, M.] Dana Farber Canc Inst, Surg, Boston, MA 02115 USA. [Miceli, R.] Fdn IRCCS Ist Nazl Tumori, Biostat, Milan, Italy. [Strauss, D.; Hayes, A.] Royal Marsden Hosp NHS Fdn Trust, Surg, London, England. [Swallow, C.; Cannell, A.] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Swallow, C.; Cannell, A.] Princess Margaret Canc Ctr, Surg Oncol, Toronto, ON, Canada. [Hohenberger, P.; Jakob, J.] Mannheim Univ Hosp, Surg Oncol & Thorac Surg, Mannheim, Germany. [Van Coevorden, F.] Netherlands Canc Inst, Surg Oncol, Amsterdam, Netherlands. [Rutkowski, P.; Szacht, M.] Maria Sklodowska Curie Mem Canc Ctr, Warsaw, Poland. [Rutkowski, P.; Szacht, M.] Inst Oncol, Soft Tissue Bone Sarcoma & Melanoma, Warsaw, Poland. [Fiore, M.; Callegaro, D.; Gronchi, A.] Fdn IRCCS Ist Nazl Tumori, Surg, Milan, Italy. [Casali, P.] Fdn IRCCS Ist Nazl Tumori, Canc Med, Milan, Italy. [Haas, R.] Netherlands Canc Inst, Radiat Oncol, Amsterdam, Netherlands. [Honore, C.] Inst Gustave Roussy, Surg, Villejuif, France. [Pollock, R.] Ohio State Univ, Med Ctr, Surg, Columbus, OH 43210 USA. [Bonvalot, S.] Hop Inst Curie, Surg, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 3404 BP S689 EP S690 PG 2 WC Oncology SC Oncology GA CS2GP UT WOS:000361887403200 ER PT J AU Ferreira, AR Palha, A Correia, L Filipe, P Rodrigues, V Costa, L Miranda, A Andre, R Fernandes, J Gouveia, J Coelho, JLP Moreira, A Brito, M Ribeiro, J Freedman, R Metzger, O Lin, NU Vaz-Luis, I AF Rebelo Ferreira, A. Palha, A. Correia, L. Filipe, P. Rodrigues, V. Costa, L. Miranda, A. Andre, R. Fernandes, J. Gouveia, J. Passos Coelho, J. L. Moreira, A. Brito, M. Ribeiro, J. Freedman, R. Metzger-Filho, O. Lin, N. U. Vaz-Luis, I. TI The use of trastuzumab in patients with early breast cancer: A multi-institutional study SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Rebelo Ferreira, A.] Hosp Santa Maria, Inst Med Mol, Dana Farber Canc Inst, Med Oncol, Lisbon, Portugal. [Palha, A.; Correia, L.] Hosp Santa Maria, Dept Pathol, Lisbon, Portugal. [Filipe, P.] Hosp Santa Maria, Med Oncol, Lisbon, Portugal. [Rodrigues, V.] Hosp Santa Maria, Dept Pharm, Lisbon, Portugal. [Costa, L.] Hosp Santa Maria, Inst Med Mol, Med Oncol, Lisbon, Portugal. [Miranda, A.; Andre, R.] Registo Oncol Reg Sul, Lisbon, Portugal. [Fernandes, J.; Gouveia, J.] Hosp CUF Lisboa Descobertas & Infante Santo, Med Occol, Lisbon, Portugal. [Passos Coelho, J. L.] Hosp Luz, Med Oncol, Lisbon, Portugal. [Moreira, A.; Brito, M.] Inst Portugues Oncol Lisboa FG, Med Oncol, Lisbon, Portugal. [Ribeiro, J.] Fundacao Champalimaud, Med Oncol, Lisbon, Portugal. [Freedman, R.; Metzger-Filho, O.; Lin, N. U.; Vaz-Luis, I.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 1962 BP S320 EP S320 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887401331 ER PT J AU Ferreira, AR Palha, A Correia, L Filipe, P Rodrigues, V Costa, L Miranda, A Andre, R Fernandes, J Gouveia, J Coelho, JLP Moreira, A Brito, M Ribeiro, J Metzger, O Lin, NU Vaz-Luis, I AF Rebelo Ferreira, A. Palha, A. Correia, L. Filipe, P. Rodrigues, V. Costa, L. Miranda, A. Andre, R. Fernandes, J. Gouveia, J. Passos Coelho, J. L. Moreira, A. Brito, M. Ribeiro, J. Metzger-Filho, O. Lin, N. U. Vaz-Luis, I. TI Variation in the chemotherapy use patterns for patients with stage I breast cancer: A multi-institutional study SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Rebelo Ferreira, A.] Hosp Santa Maria, Inst Med Mol, Dana Farber Canc Inst, Med Oncol, Lisbon, Portugal. [Palha, A.; Correia, L.] Hosp Santa Maria, Dept Pathol, Lisbon, Portugal. [Filipe, P.] Hosp Santa Maria, Med Oncol, Lisbon, Portugal. [Rodrigues, V.] Hosp Santa Maria, Dept Pharm, Lisbon, Portugal. [Costa, L.] Hosp Santa Maria, Inst Med Mol, Med Oncol, Lisbon, Portugal. [Miranda, A.; Andre, R.] Registo Oncol Reg Sul, Lisbon, Portugal. [Fernandes, J.; Gouveia, J.] Hosp CUF Lisboa Descobertas & Infante Santo, Med Oncol, Lisbon, Portugal. [Passos Coelho, J. L.] Hosp Luz, Med Oncol, Lisbon, Portugal. [Moreira, A.; Brito, M.] Inst Portugues Oncol Lisboa FG, Med Oncol, Lisbon, Portugal. [Ribeiro, J.] Fundacao Champalimaud, Med Oncol, Lisbon, Portugal. [Metzger-Filho, O.; Lin, N. U.; Vaz-Luis, I.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 1961 BP S320 EP S320 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887401330 ER PT J AU Sartor, O Coleman, RE Morris, MJ Nilsson, S Shore, N Sweeney, C Vogelzang, NJ Petrenciuc, O Gratt, J Parker, C AF Sartor, O. Coleman, R. E. Morris, M. J. Nilsson, S. Shore, N. Sweeney, C. Vogelzang, N. J. Petrenciuc, O. Gratt, J. Parker, C. TI Baseline characteristics, number of radium-223 (Ra-223) injections, and overall survival (OS) in US Expanded Access Program (EAP) and ALSYMPCA SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Sartor, O.] Tulane Canc Ctr, Dept Med, New Orleans, LA USA. [Sartor, O.] Tulane Canc Ctr, Dept Urol, New Orleans, LA USA. [Coleman, R. E.] Univ Sheffield, Acad Unit Clin Oncol, Weston Pk Hosp, Sheffield, S Yorkshire, England. [Morris, M. J.] Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, New York, NY 10021 USA. [Nilsson, S.] Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden. [Shore, N.] Carolina Urol Res Ctr, Dept Med Oncol, Myrtle Beach, SC USA. [Sweeney, C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Vogelzang, N. J.] Comprehens Canc Ctr Nevada, Dept Med Oncol, Las Vegas, NV USA. [Petrenciuc, O.] Bayer HealthCare, Dept Global Clin Dev, Whippany, NJ USA. [Gratt, J.] Bayer HealthCare, Dept Global Data Sci & Analyt, Whippany, NJ USA. [Parker, C.] Royal Marsden NHS Fdn Trust, Sutton, Surrey, England. [Parker, C.] Inst Canc Res, Acad Urol Unit, Sutton, Surrey, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 2530 BP S484 EP S485 PG 2 WC Oncology SC Oncology GA CS2GP UT WOS:000361887402233 ER PT J AU Schwartz, G Adkins, D Heist, R Werner, T Abbott, M Barber, S Slusarz, K Agarwal, N Neuteboom, S Faltaos, D Chen, I Christensen, J Chao, R Bauer, T AF Schwartz, G. Adkins, D. Heist, R. Werner, T. Abbott, M. Barber, S. Slusarz, K. Agarwal, N. Neuteboom, S. Faltaos, D. Chen, I. Christensen, J. Chao, R. Bauer, T. TI A first-in-human phase 1/1b study of receptor tyrosine kinase (RTK) inhibitor, MGCD516, in patients with advanced solid tumors SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Schwartz, G.; Abbott, M.] Columbia Univ, Div Hematol & Oncol, Med Ctr, New York, NY USA. [Adkins, D.; Barber, S.] Washington Univ, Sch Med, Div Oncol, St Louis, MO USA. [Heist, R.; Slusarz, K.] Massachusetts Gen Hosp, Ctr Canc, Hematol Oncol, Boston, MA USA. [Werner, T.; Agarwal, N.] Huntsman Canc Inst, Div Oncol, Salt Lake City, UT USA. [Neuteboom, S.; Faltaos, D.; Chen, I.; Chao, R.] Mirati Therapeut, Clin Sci, San Diego, CA USA. [Christensen, J.] Mirati Therapeut, Discovery & Translat Sci, San Diego, CA USA. [Bauer, T.] Tennessee Oncol PLLC, Oncol, Sarah Cannon Res Inst, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 370 BP S78 EP S78 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887400239 ER PT J AU Sharma, P Escudier, B McDermott, DF George, S Hammers, HJ Srinivas, S Tykodi, SS Sosman, JA Procopio, G Plimack, ER Castellano, D Gurney, H Donskov, F Bono, P Wagstaff, J Gauler, TC Ueda, T Xu, LA Waxman, IM Motzer, RJ AF Sharma, P. Escudier, B. McDermott, D. F. George, S. Hammers, H. J. Srinivas, S. Tykodi, S. S. Sosman, J. A. Procopio, G. Plimack, E. R. Castellano, D. Gurney, H. Donskov, F. Bono, P. Wagstaff, J. Gauler, T. C. Ueda, T. Xu, L. A. Waxman, I. M. Motzer, R. J. TI CheckMate 025: a randomized, open-label, phase III study of nivolumab (NIVO) versus everolimus (EVE) in advanced renal cell carcinoma (RCC) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Sharma, P.] Univ Texas MD Anderson Canc Ctr, Genitourinary Med Oncol, Houston, TX 77030 USA. [Escudier, B.] Inst Gustave Roussy, Oncol, Villejuif, France. [McDermott, D. F.] Beth Israel Deaconess Med Ctr, Dana Farber Harvard Canc Ctr, Hematol Internal Med Oncol, Boston, MA 02215 USA. [George, S.] Roswell Pk Canc Inst, Oncol, Buffalo, NY 14263 USA. [Hammers, H. J.] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Oncol, Baltimore, MD USA. [Srinivas, S.] Stanford Canc Inst, Hematol Internal Med Oncol, Stanford, CA USA. [Tykodi, S. S.] Univ Washington, Seattle, WA 98195 USA. [Tykodi, S. S.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Sosman, J. A.] Vanderbilt Univ, Med Ctr, Oncol, Nashville, TN USA. [Procopio, G.] Fdn Ist Nazl Tumori, Oncol, Milan, Italy. [Plimack, E. R.] Fox Chase Canc Ctr, Internal Med Oncol, Philadelphia, PA 19111 USA. [Castellano, D.] Hosp Univ 12 Octubre, Oncol, Madrid, Spain. [Gurney, H.] Westmead Hosp, Oncol, Westmead, NSW, Australia. [Donskov, F.] Aarhus Univ Hosp, Oncol, DK-8000 Aarhus, Denmark. [Bono, P.] Helsinki Univ Hosp, Ctr Comprehens Canc, Helsinki, Finland. [Bono, P.] Univ Helsinki, Oncol Radiat Oncol, Helsinki, Finland. [Wagstaff, J.] South West Wales Canc Inst, Swansea, W Glam, Wales. [Wagstaff, J.] Swansea Univ, Coll Med, Oncol, Swansea, W Glam, Wales. [Gauler, T. C.] Univ Duisburg Essen, Univ Hosp Essen, Oncol, Essen, Germany. [Ueda, T.] Chiba Canc Ctr, Oncol, Chiba 2608717, Japan. [Xu, L. A.] Bristol Myers Squibb, Global Biometr Sci Oncol, Hopewell, NJ USA. [Waxman, I. M.] Bristol Myers Squibb Co, Lawrenceville, NJ USA. [Motzer, R. J.] Mem Sloan Kettering Canc Ctr, Internal Med Oncol, New York, NY 10021 USA. NR 0 TC 0 Z9 1 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 3LBA BP S708 EP S708 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887403249 ER PT J AU Shinozaki, E Laurent, S Gravalos, C Benavides, M Munoz, FL Mizuguchi, H Wahba, M Ychou, M Ciardiello, F Siena, S Yamaguchi, K Muro, K Denda, T Tsuji, Y Loehrer, P Lenz, HJ Tebbutt, N Mayer, RJ Van Cutsem, E Ohtsu, A AF Shinozaki, E. Laurent, S. Gravalos, C. Benavides, M. Longo Munoz, F. Mizuguchi, H. Wahba, M. Ychou, M. Ciardiello, F. Siena, S. Yamaguchi, K. Muro, K. Denda, T. Tsuji, Y. Loehrer, P. Lenz, H. J. Tebbutt, N. Mayer, R. J. Van Cutsem, E. Ohtsu, A. TI Timing of adverse events (AEs) in the Phase 3 RECOURSE trial of TAS-102 versus placebo in patients (pts) with metastatic colorectal cancer (mCRC) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Shinozaki, E.] Japanese Fdn Canc Res, Canc Inst Hosp, GI Oncol Dept, Tokyo, Japan. [Laurent, S.] Univ Hosp Ghent, Dept Gastroenterol, Ghent, Belgium. [Gravalos, C.] Hosp Univ 12 Octubre, Dept Med Oncol, Madrid, Spain. [Benavides, M.] Hosp Reg Univ Malaga, Med Oncol Unit, Malaga, Spain. [Longo Munoz, F.] Hosp Univ Ramon & Cajal, Serv Oncol & Medica, Serv Oncol Med, Madrid, Spain. [Mizuguchi, H.] Taiho Oncol Inc, Oncol, Princeton, NJ USA. [Wahba, M.] Taiho Oncol Inc, Med Affairs & Med Pharmacovigilance, Princeton, NJ USA. [Ychou, M.] Inst Reg Canc Med A2, Montpellier, France. [Ciardiello, F.] Univ Naples 2, Dipartimento Internist Clin & Sperimentale, Naples, Italy. [Siena, S.] Osped Niguarda Ca Granda, Niguarda Canc Ctr, Milan, Italy. [Yamaguchi, K.] Saitama Canc Ctr, Dept Gastroenterol, Saitama, Japan. [Muro, K.] Aichi Canc Ctr Hosp, Dept Clin Oncol, Aichi, Japan. [Denda, T.] Chiba Canc Ctr, Div Gastroenterol, Chiba, Japan. [Tsuji, Y.] Tonan Hosp, KKR Sapporo Med Ctr, Hokkaido, Japan. [Loehrer, P.] Indiana Univ Hlth, Melvin & Bren Simon Canc Ctr, Indianapolis, IN USA. [Lenz, H. J.] Yale Canc Ctr, Gastrointestinal Canc Program, New Haven, CT USA. [Tebbutt, N.] Austin Hosp, Med Oncol, Heidelberg, Vic, Australia. [Mayer, R. J.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Van Cutsem, E.] Univ Hosp Gasthuisberg, Gastroenterol Digest Oncol, Leuven, Belgium. [Ohtsu, A.] Natl Canc Ctr Hosp East, Dept GI Oncol, Kashiwa, Chiba, Japan. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 2151 BP S383 EP S384 PG 2 WC Oncology SC Oncology GA CS2GP UT WOS:000361887401497 ER PT J AU Siena, S Drilon, AE Ou, ISH Farago, AF Patel, M Bauer, TM Hong, D Liu, SV Lee, J Patel, R Schechet, L Luo, D Maneval, EC Multani, PS De Braud, FG AF Siena, S. Drilon, A. E. Ou, I. Sai-Hong Farago, A. F. Patel, M. Bauer, T. M. Hong, D. Liu, S. V. Lee, J. Patel, R. Schechet, L. Luo, D. Maneval, E. Chow Multani, P. S. De Braud, F. G. TI Entrectinib (RXDX-101), an oral pan-Trk, ROS1, and ALK inhibitor in patients with advanced solid tumors harboring gene rearrangements SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Siena, S.] Osped Niguarda Ca Granda, Niguarda Canc Ctr, Milan, Italy. [Siena, S.] Univ Milan, Oncol, Milan, Italy. [Drilon, A. E.] Mem Sloan Kettering Canc Ctr, Dev Therapeut, New York, NY 10021 USA. [Ou, I. Sai-Hong] Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Med Oncol, Orange, CA USA. [Farago, A. F.] Massachusetts Gen Hosp, Ctr Canc, Ctr Thorac Canc, Boston, MA USA. [Patel, M.] Florida Canc Specialists, Oncol, Sarasota, FL USA. [Bauer, T. M.] Tenessee Oncol, Med Oncol, Nashville, TN USA. [Hong, D.] Univ Texas MD Anderson Canc Ctr, Invest Canc Therapeut, Houston, TX 77030 USA. [Liu, S. V.] Georgetown Lombardi Comprehens Canc Ctr, Oncol, Washington, DC USA. [Lee, J.] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Hematol Oncol, Seoul, South Korea. [Patel, R.; Schechet, L.; Luo, D.; Maneval, E. Chow; Multani, P. S.] Ignyta Inc, Clin Dev, San Diego, CA USA. [De Braud, F. G.] Fdn IRCCS Ist Nazl Tumori Milano, Med Oncol, Milan, Italy. NR 0 TC 5 Z9 5 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 29LBA BP S724 EP S725 PG 2 WC Oncology SC Oncology GA CS2GP UT WOS:000361887403280 ER PT J AU Solomon, B Wakelee, H Sequist, LV Gadgeel, S Soria, JC Goldman, JW Yu, H Camidge, DR Papadimitrakopoulou, V Matheny, S Despain, D Besse, B AF Solomon, B. Wakelee, H. Sequist, L. V. Gadgeel, S. Soria, J. C. Goldman, J. W. Yu, H. Camidge, D. R. Papadimitrakopoulou, V. Matheny, S. Despain, D. Besse, B. TI Rociletinib treatment and outcomes in non-small cell lung cancer (NSCLC) patients with negative central testing for T790M SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Solomon, B.] Peter MacCallum Canc Ctr, Mol Therapeut & Biomarkers, Melbourne, Vic, Australia. [Wakelee, H.] Stanford Univ, Med Ctr, Thorac Oncol, Stanford, CA 94305 USA. [Sequist, L. V.] Massachusetts Gen Hosp, Med Oncol, Boston, MA 02114 USA. [Gadgeel, S.] Karmanos Canc Ctr, Clin Arrangements, Detroit, MI USA. [Soria, J. C.] Gustave Roussy Canc Ctr, Drug Dev, Villejuif, France. [Goldman, J. W.] UCLA Med Ctr, Med, Hematol & Oncol, Santa Monica, CA USA. [Yu, H.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Camidge, D. R.] Univ Colorado, Thorac Oncol, Denver, CO 80202 USA. [Papadimitrakopoulou, V.] Univ Texas MD Anderson Canc Ctr, Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. [Matheny, S.] Clovis Oncol, Clin Sci, San Francisco, CA USA. [Despain, D.] Clovis Oncol, Biostat, San Francisco, CA USA. [Besse, B.] Gustave Roussy Canc Ctr, Med Oncol, Villejuif, France. NR 0 TC 1 Z9 1 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 3104 BP S636 EP S636 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887403062 ER PT J AU Soria, JC Flotten, O Horn, L Felip, E Gandhi, L Hui, R Hellmann, M Leighl, N Zhang, J Kondic, A Rangwala, R Lubiniecki, GM Garon, EB AF Soria, J. C. Flotten, O. Horn, L. Felip, E. Gandhi, L. Hui, R. Hellmann, M. Leighl, N. Zhang, J. Kondic, A. Rangwala, R. Lubiniecki, G. M. Garon, E. B. TI Efficacy and Safety of Pembrolizumab (Pembro; MK-3475) for Patients (Pts) With Previously Treated Advanced Non-Small Cell Lung Cancer (NSCLC) Enrolled in KEYNOTE-001 SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Soria, J. C.] Inst Gustave Roussy, Med Oncol Lung Unit, Villejuif, France. [Flotten, O.] Haukeland Hosp, Dept Thorac Med, N-5021 Bergen, Norway. [Horn, L.] Vanderbilt Ingram Canc Ctr, Hematol Oncol, Nashville, TN USA. [Felip, E.] Vall dHebron Univ Hosp, Oncol Serv, Barcelona, Spain. [Gandhi, L.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Hui, R.] Westmead Hosp, Dept Med Oncol, Sydney, NSW, Australia. [Hellmann, M.] Mem Sloan Kettering Canc Ctr, Dept Med, Thorac Oncol Serv, New York, NY 10021 USA. [Leighl, N.] Princess Margaret Hosp, Canc Clin Res Unit, Toronto, ON M4X 1K9, Canada. [Zhang, J.] Merck & Co Inc, BARDS, Kenilworth, NJ USA. [Kondic, A.] Merck & Co Inc, Quantitat Pharmacol & Pharmacometr, Kenilworth, NJ USA. [Rangwala, R.; Lubiniecki, G. M.] Merck & Co Inc, Clin Res Oncol, Kenilworth, NJ USA. [Garon, E. B.] Univ Calif Los Angeles, David Geffen Sch Med, Med Div Heme Onc, Los Angeles, CA 90095 USA. RI Zhang, Jin/E-8298-2017 NR 0 TC 1 Z9 1 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 33LBA BP S726 EP S727 PG 4 WC Oncology SC Oncology GA CS2GP UT WOS:000361887403284 ER PT J AU Soria, JC Goldman, JW Wakelee, H Gadgeel, S Camidge, DR Solomon, B Yu, H Oxnard, GR Ou, SH Papadimitrakopoulou, V Perol, M Reckamp, K Varga, A Dziadziuszko, R Chouaid, C Cortot, A Do, P Moro-Sibilot, D Poudenx, M Sequist, LV AF Soria, J. C. Goldman, J. W. Wakelee, H. Gadgeel, S. Camidge, D. R. Solomon, B. Yu, H. Oxnard, G. R. Ou, S. H. Papadimitrakopoulou, V. Perol, M. Reckamp, K. Varga, A. Dziadziuszko, R. Chouaid, C. Cortot, A. Do, P. Moro-Sibilot, D. Poudenx, M. Sequist, L. V. TI Dose optimization of rociletinib for EGFR mutated NSCLC: Benefit/risk analysis from the TIGER-X trial SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Soria, J. C.] Gustave Roussy Canc Ctr, Drug Dev, Villejuif, France. [Goldman, J. W.] UCLA Med Ctr, Med Hematol & Oncol, Santa Monica, CA USA. [Wakelee, H.] Stanford Univ, Med Ctr, Thorac Oncol, Stanford, CA 94305 USA. [Gadgeel, S.] Karmanos Canc Ctr, Clin Arrangements, Detroit, MI USA. [Camidge, D. R.] Univ Colorado, Thorac Oncol, Denver, CO 80202 USA. [Solomon, B.] Peter MacCallum Canc Ctr, Mol Therapeut & Biomarkers, Meblourne, Vic, Australia. [Yu, H.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Oxnard, G. R.] Dana Farber Canc Inst, Thorac Oncol, Boston, MA 02115 USA. [Ou, S. H.] Univ Calif Irvine, Hematol Oncol, Orange, CA USA. [Papadimitrakopoulou, V.] Univ Texas MD Anderson Canc Ctr, Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. [Perol, M.] Canc Res Ctr, Oncol, Lyon, France. [Reckamp, K.] City Hope Comprehens Canc Ctr, Lung Canc & Thorac Oncol, Duarte, CA USA. [Varga, A.] Gustave Roussy Canc Ctr, Dept Med, Villejuif, France. [Dziadziuszko, R.] Med Univ Gdansk, Dept Radiotherapy & Oncol, Gdansk, Poland. [Chouaid, C.] Ctr Hosp Intercommunal Creteil, Pulmonol, Creteil, France. [Cortot, A.] Ctr Hosp Reg Univ Lille, Pulmonol, Lille, France. [Do, P.] Ctr Francois Baclesse, Pulmonol, F-14021 Caen, France. [Moro-Sibilot, D.] Ctr Hosp Univ Grenoble, Pulmonol, Grenoble, France. [Poudenx, M.] Ctr Antoine Lacassagne, Med Oncol, F-06054 Nice, France. [Sequist, L. V.] Massachusetts Gen Hosp, Med Oncol, Boston, MA 02114 USA. RI CORTOT, ANTOINE/I-7739-2016 OI CORTOT, ANTOINE/0000-0002-1067-8996 NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 3105 BP S637 EP S637 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887403063 ER PT J AU Sparano, J Gray, R Zujewski, JA Makower, D Pritchard, K Albain, K Hayes, D Geyer, C Dees, C Perez, E Keane, M Vallejos, C Goggins, T Mayer, I Brufsky, A Toppmeyer, D Kaklamani, V Atkins, J Olson, J Sledge, G AF Sparano, J. Gray, R. Zujewski, J. A. Makower, D. Pritchard, K. Albain, K. Hayes, D. Geyer, C. Dees, C. Perez, E. Keane, M. Vallejos, C. Goggins, T. Mayer, I. Brufsky, A. Toppmeyer, D. Kaklamani, V. Atkins, J. Olson, J. Sledge, G. TI Prospective trial of endocrine therapy alone in patients with estrogen-receptor positive, HER2-negative, node-negative breast cancer: Results of the TAILORx low risk registry SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Sparano, J.; Makower, D.] Albert Einstein Coll Med, Montefiore Med Ctr, Dept Oncol, New York, NY USA. [Gray, R.] Dana Farber Canc Inst, Biostat, Boston, MA 02115 USA. [Zujewski, J. A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Pritchard, K.] Sunnybrook Odette Canc Ctr, Oncol, Toronto, ON, Canada. [Albain, K.] Loyola Univ, Chicago Stritch Sch Med, Oncol, Maywood, IL USA. [Hayes, D.] Univ Michigan, Oncol, Ann Arbor, MI 48109 USA. [Geyer, C.] Virginia Commonwealth Univ, Massey Canc Ctr, Oncol, Richmond, VA USA. [Dees, C.] Univ N Carolina, Oncol, Chapel Hill, NC USA. [Perez, E.] Mayo Clin, Oncol, Jacksonville, FL 32224 USA. [Keane, M.] West Ireland Canc Ctr, Oncol, Galway, Ireland. [Vallejos, C.] Inst Nacl Enfermedades Neoplas, Oncol, Lim, Peru. [Goggins, T.] Fox Valley Hematol Oncol, Oncol, Appleton, WI USA. [Mayer, I.] Vanderbilt Ingram Canc Ctr, Oncol, Nashville, TN USA. [Brufsky, A.] Magee Womens Hosp, Oncol, Pittsburgh, PA USA. [Toppmeyer, D.] Canc Inst New Jersey, New Brunswick, NJ USA. [Kaklamani, V.] Northwestern Univ, Oncol, Chicago, IL 60611 USA. [Atkins, J.] Southeastern Med Ctr, Oncol, Goldsboro, NC USA. [Olson, J.] Univ Maryland, Baltimore, MD 21201 USA. [Sledge, G.] Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 5BA BP S714 EP S714 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887403260 ER PT J AU Strosberg, J Wolin, E Chasen, B Kulke, M Bushnell, D Caplin, M Baum, RP Mittra, E Hobday, T Hendifar, A Oberg, K Sierra, ML Ruszniewski, P Kwekkeboom, D AF Strosberg, J. Wolin, E. Chasen, B. Kulke, M. Bushnell, D. Caplin, M. Baum, R. P. Mittra, E. Hobday, T. Hendifar, A. Oberg, K. Sierra, M. Lopera Ruszniewski, P. Kwekkeboom, D. TI 177-Lu-Dotatate significantly improves progression-free survival in patients with midgut neuroendocrine tumours: Results of the phase III NETTER-1 trial SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Strosberg, J.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Med Oncol & Hematol, Tampa, FL 33612 USA. [Wolin, E.] Univ Kentucky, Markey Canc Ctr, GI Carcinoid & Neuroendocrine Canc, Lexington, KY 40506 USA. [Chasen, B.] Univ Texas MD Anderson Canc Ctr, Dept Nucl Med, Houston, TX 77030 USA. [Kulke, M.] Dana Farber Canc Inst, Neuroendocrine & Carcinoid Tumors, Boston, MA 02115 USA. [Bushnell, D.] Univ Iowa, Carver Coll Med, Div Nucl Med, Iowa City, IA USA. [Caplin, M.] Royal Free Hosp, Gastroenterol & Gastrointestinal Neuroendocrinol, London NW3 2QG, England. [Baum, R. P.] Ctr Neuroendocrine Tumors, Zent Klin, Bad Berka, Germany. [Mittra, E.] Stanford Univ, Med Ctr, Radiol & Nucl Med, Stanford, CA 94305 USA. [Hobday, T.] Mayo Clin, Coll Med, Hematol & Oncol, Rochester, MN USA. [Hendifar, A.] Cedars Sinai Med Ctr, Gastrointestinal Oncol, Los Angeles, CA 90048 USA. [Oberg, K.] Univ Uppsala Hosp, Endocrine Oncol, Uppsala, Sweden. [Sierra, M. Lopera] Adv Accelerator Applicat, Clin Dev, New York, NY USA. [Ruszniewski, P.] Hop Beaujon, Gastroenterol & Pancreatol, Clichy, France. [Kwekkeboom, D.] Erasmus MC, Nucl Med, Rotterdam, Netherlands. NR 0 TC 8 Z9 8 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 6LBA BP S710 EP S710 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887403253 ER PT J AU Vale, C Rydzewska, LH Tierney, JF Albiges, L Clarke, NW Fisher, DJ Fizazi, K James, ND Mason, MD Parmar, MK Sweeney, CJ Sydes, MR Tombal, B Burdett, S AF Vale, C. Rydzewska, L. H. Tierney, J. F. Albiges, L. Clarke, N. W. Fisher, D. J. Fizazi, K. James, N. D. Mason, M. D. Parmar, M. K. Sweeney, C. J. Sydes, M. R. Tombal, B. Burdett, S. TI What is the current evidence for adding docetaxel or bisphosphonates to androgen deprivation therapy (ADT) in men with hormone sensitive prostate cancer? A systematic review and meta-analyses SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Vale, C.; Rydzewska, L. H.; Tierney, J. F.; Fisher, D. J.; Burdett, S.] UCL, MRC Clin Trials Unit, Meta Anal Grp, London, England. [Albiges, L.; Fizazi, K.] Inst Gustave Roussy, Dept Med Oncol, Paris, France. [Clarke, N. W.] Christie NHS Fdn Trust, Dept Urol, Manchester, Lancs, England. [James, N. D.] Univ Warwick, Warwick Canc Res Unit, Coventry CV4 7AL, W Midlands, England. [Mason, M. D.] Cardiff Univ, Sch Med, Velindre Hosp, Cardiff CF10 3AX, S Glam, Wales. [Parmar, M. K.] UCL, Inst Clin Trials & Methodol, MRC Clin Trials Unit, London, England. [Sweeney, C. J.] Dana Farber Canc Inst, Lank Ctr Genitourinary Canc, Boston, MA 02115 USA. [Sydes, M. R.] UCL, MRC Clin Trials Unit, Canc & Noninfect Dis Grp, London, England. [Tombal, B.] Catholic Univ Louvain, Clin Univ St Luc, B-1200 Brussels, Belgium. NR 0 TC 0 Z9 0 U1 3 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 20LBA BP S719 EP S720 PG 2 WC Oncology SC Oncology GA CS2GP UT WOS:000361887403271 ER PT J AU Van den Bent, MJ Roberts-Rapp, L Ansell, P Kular, R Song, M Sokolova, I Gan, H Papadopoulos, KP Lassman, AB Merrell, R Kumthekar, P Scott, A Gomez, E Fischer, J Bhathena, A Holen, K Lai, R Reardon, D AF Van den Bent, M. J. Roberts-Rapp, L. Ansell, P. Kular, R. Song, M. Sokolova, I. Gan, H. Papadopoulos, K. P. Lassman, A. B. Merrell, R. Kumthekar, P. Scott, A. Gomez, E. Fischer, J. Bhathena, A. Holen, K. Lai, R. Reardon, D. TI Identifying the correct patient (pt) population for ABT-414: Biomarker assays for epidermal growth factor receptor (EGFR) in pts with glioblastoma (GBM) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Van den Bent, M. J.] Erasmus MC Canc Ctr, Neurooncol, Rotterdam, Netherlands. [Roberts-Rapp, L.; Ansell, P.; Gomez, E.; Fischer, J.; Bhathena, A.; Holen, K.; Lai, R.] AbbVie Inc, N Chicago, IL USA. [Kular, R.; Song, M.; Sokolova, I.] Abbott Mol Inc, Des Plaines, IL USA. [Gan, H.; Scott, A.] Austin Hlth, Melbourne, Vic, Australia. [Gan, H.; Scott, A.] Olivia Newton John Canc Res Inst, Melbourne, Vic, Australia. [Papadopoulos, K. P.] South Texas Accelerated Res Therapeut, San Antonio, TX USA. [Lassman, A. B.] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA. [Lassman, A. B.] Herbert Irving Comprehens Canc Ctr, New York, NY USA. [Merrell, R.] NorthShore Univ Hlth Syst, Evanston, IL USA. [Kumthekar, P.] Northwestern Univ, Chicago, IL 60611 USA. [Reardon, D.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 2903 BP S585 EP S585 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887402509 ER PT J AU Varga, A Camidge, DR Sequist, LV Wakelee, H Ou, SH Goldman, JW Papadimitrakopoulou, V Gadgeel, S Mekhail, T Oxnard, GR Socinski, M Solomon, B Yu, H Matheny, S Despain, D Soria, JC AF Varga, A. Camidge, D. R. Sequist, L. V. Wakelee, H. Ou, S. H. Goldman, J. W. Papadimitrakopoulou, V. Gadgeel, S. Mekhail, T. Oxnard, G. R. Socinski, M. Solomon, B. Yu, H. Matheny, S. Despain, D. Soria, J. C. TI Activity of rociletinib in EGFR mutant NSCLC patients with a history of CNS involvement SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Varga, A.] Gustave Roussy Canc Ctr, Dept Med, Villejuif, France. [Camidge, D. R.] Univ Colorado Denver, Thorac Oncol, Denver, CO USA. [Sequist, L. V.] Massachusetts Gen Hosp, Med Oncol, Boston, MA 02114 USA. [Wakelee, H.] Stanford Univ, Med Ctr, Thorac Oncol, Stanford, CA 94305 USA. [Ou, S. H.] Univ Calif Irvine, Hematol Oncol, Irvine, CA USA. [Goldman, J. W.] Univ Calif Los Angeles, Med Ctr, Med Hematol & Oncol, Santa Monica, CA USA. [Papadimitrakopoulou, V.] Univ Texas MD Anderson Canc Ctr, Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. [Gadgeel, S.] Karmanos Canc Ctr, Clin Arrangements, Detroit, MI USA. [Mekhail, T.] Florida Hosp, Hematol & Oncol, Inst Canc, Orlando, FL USA. [Oxnard, G. R.] Dana Farber Canc Inst, Thorac Oncol, Boston, MA 02115 USA. [Socinski, M.] Univ Pittsburgh, Hematol Oncol, Pittsburgh, PA USA. [Solomon, B.] Peter MacCallum Canc Ctr, Mol Therapeut & Biomarkers, Melbourne, Australia. [Yu, H.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Matheny, S.] Clovis Oncol, Clin Sci, San Francisco, CA USA. [Despain, D.] Clovis Oncol, Biostat, Boulder, CO USA. [Soria, J. C.] Gustave Roussy Canc Ctr, Drug Dev, Villejuif, France. NR 0 TC 3 Z9 3 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 3009 BP S598 EP S598 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887402546 ER PT J AU Von Mehren, M Demetri, GD Schuetze, SM Jones, RL Milhem, M Elias, A Van Tine, BA Hamm, J Khokhar, NZ McCarthy, S Park, YC Knoblauch, RE Parekh, TV Maki, RG Patel, SR AF Von Mehren, M. Demetri, G. D. Schuetze, S. M. Jones, R. L. Milhem, M. Elias, A. Van Tine, B. A. Hamm, J. Khokhar, N. Z. McCarthy, S. Park, Y. C. Knoblauch, R. E. Parekh, T. V. Maki, R. G. Patel, S. R. TI Efficacy and safety of trabectedin (T) or dacarbazine (D) in an elderly patient subgroup (>= 65 years) with advanced leiomyosarcoma (LMS) or liposarcoma (LPS) after prior chemotherapy SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Von Mehren, M.] Fox Chase Canc Ctr, Med Oncol, Philadelphia, PA 19111 USA. [Demetri, G. D.] Harvard, Ctr Sarcoma & Bone Oncol, Dana Farber Canc Inst, Boston, MA USA. [Demetri, G. D.] Harvard, Ctr Sarcoma & Bone Oncol, Ludwig Ctr, Boston, MA USA. [Schuetze, S. M.] Univ Michigan, Med Oncol, Ann Arbor, MI 48109 USA. [Jones, R. L.] Seattle Canc Care Alliance, Oncol, Seattle, WA USA. [Milhem, M.] Univ Iowa Hosp & Clin, Holden Comprehens Canc Ctr, Clin Serv, Iowa City, IA 52242 USA. [Elias, A.] Univ Colorado, Ctr Canc, Med Oncol, Aurora, CO USA. [Van Tine, B. A.] Washington Univ, Div Med Oncol, Sect Med Oncol, St Louis, MO USA. [Hamm, J.] Norton Canc Inst, Med Oncol, Louisville, KY USA. [Khokhar, N. Z.; McCarthy, S.; Knoblauch, R. E.; Parekh, T. V.] Janssen Res & Dev LLC, Clin Oncol, Raritan, NJ USA. [Park, Y. C.] Janssen Res & Dev LLC, Clin Biostat, Raritan, NJ USA. [Maki, R. G.] Mt Sinai Sch Med, Hematol Oncol, New York, NY USA. [Patel, S. R.] Univ Texas MD Anderson Canc Ctr, Dept Sarcoma Med Oncol, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 1321 BP S194 EP S194 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887400583 ER PT J AU Voss, M Gordon, MS Mita, M Rini, B Makker, V Macarulla, T Smith, D Kwak, EL Cervantes, A Puzanov, I Pili, R Wang, D Jalal, S Pant, S Patel, M Neuwirth, R Zohren, F Infante, J AF Voss, M. Gordon, M. S. Mita, M. Rini, B. Makker, V. Macarulla, T. Smith, D. Kwak, E. L. Cervantes, A. Puzanov, I. Pili, R. Wang, D. Jalal, S. Pant, S. Patel, M. Neuwirth, R. Zohren, F. Infante, J. TI Phase I study of investigational oral mTORC1/2 inhibitor MLN0128: Expansion phase in patients with renal, endometrial, or bladder cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Voss, M.] Mem Sloan Kettering Canc Ctr, Dept Med, Div Solid Tumor Oncol Genitourinary Oncol, New York, NY 10021 USA. [Gordon, M. S.] Pinnacle Oncol Hematol, Med Oncol, Scottsdale, AZ USA. [Mita, M.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. [Rini, B.] Cleveland Clin Fdn, Dept Solid Tumor Oncol, Cleveland, OH 44195 USA. [Makker, V.] Mem Sloan Kettering Canc Ctr, Dept Med, Div Solid Tumor Oncol, New York, NY 10021 USA. [Macarulla, T.] Vall dHebron Inst Oncol, Oncol, Barcelona, Spain. [Smith, D.] Univ Michigan, Internal Med, Ann Arbor, MI 48109 USA. [Kwak, E. L.] Massachusetts Gen Hosp, Ctr Canc, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. [Cervantes, A.] Hosp Clin Univ Valencia, Hematol & Med Oncol, Valencia, Spain. [Puzanov, I.] Vanderbilt Univ, Med Ctr, Med, Div Hematol Oncol, Nashville, TN USA. [Pili, R.] Indiana Univ, Simon Canc Ctr, Dept Med, Div Hematol Oncol, Indianapolis, IN 46204 USA. [Wang, D.] Henry Ford Hlth Syst, Hematol Oncol, Detroit, MI USA. [Jalal, S.] Indiana Univ, Melvin & Bren Simon Canc Ctr, Hematol Oncol, Indianapolis, IN 46204 USA. [Pant, S.] Oklahoma Hlth Sci Ctr, Hematol Oncol, Stephenson Canc Ctr, Oklahoma City, OK USA. [Patel, M.] Florida Canc Specialists SCRI, Drug Dev Unit, Sarasota, FL USA. [Neuwirth, R.] Millennium Pharmaceut Inc, Global Stat, Cambridge, MA USA. [Zohren, F.] Millennium Pharmaceut Inc, Oncol Clin Res, Cambridge, MA USA. [Infante, J.] Tennessee Oncol, Drug Dev Unit, Sarah Cannon Res Inst, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 354 BP S72 EP S72 PG 1 WC Oncology SC Oncology GA CS2GP UT WOS:000361887400223 ER PT J AU Yao, J Fazio, N Singh, S Buzzoni, R Carnaghi, C Wolin, E Tomasek, J Raderer, M Lahner, H Voi, M Pacaud, L Lincy, J Sachs, C Valle, J Delle Fave, G Van Cutsem, E Tesselaar, MET Shimada, Y Oh, DY Strosberg, J Kulke, MH Pavel, ME AF Yao, J. Fazio, N. Singh, S. Buzzoni, R. Carnaghi, C. Wolin, E. Tomasek, J. Raderer, M. Lahner, H. Voi, M. Pacaud, L. Lincy, J. Sachs, C. Valle, J. Delle Fave, G. Van Cutsem, E. Tesselaar, M. E. T. Shimada, Y. Oh, D. Y. Strosberg, J. Kulke, M. H. Pavel, M. E. CA RADIANT-4 Study Grp TI Everolimus in advanced nonfunctional neuroendocrine tumors (NET) of lung or gastrointestinal (GI) origin: Efficacy and safety results from the placebo-controlled, double-blind, multicenter, Phase 3 RADIANT-4 study SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT European Cancer Congress CY 2015 CL Vienna, AUSTRIA C1 [Yao, J.] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. [Fazio, N.] Ist Europeo Oncol IRCCS, Unit Med Oncol Gastrointestinal & Neuroendocrine, Milan, Italy. [Singh, S.] Sunnybrook Hlth Sci Ctr, Dept Med, Toronto, ON M4N 3M5, Canada. [Buzzoni, R.] Fdn IRCCS Ist Nazl Tumori, Dept Med Oncol, Milan, Italy. [Carnaghi, C.] IRCCS Ist Clin Humanitas, Med Oncol & Hematol Unit, Rozzano, Italy. [Wolin, E.] Univ Kentucky, Markey Canc Ctr, Neuroendocrine & Gastrointestinal Oncol, Lexington, KY 40506 USA. [Tomasek, J.] Masaryk Univ, Masaryk Mem Canc Inst, Fac Med, Dept Complex Oncol Care, Brno, Czech Republic. [Raderer, M.] Univ Klin Innere Med 1 AKH, Dept Internal Med, Vienna, Austria. [Lahner, H.] Univ Klinikum Essen, Zentrum Innere Med, Div Endocrinol & Metab Dis, Essen, Germany. [Voi, M.] Novartis Pharmaceut, Oncol Business Unit, E Hanover, NJ USA. [Pacaud, L.] Novartis Pharma AG, Oncol Business Unit, Basel, Switzerland. [Valle, J.] Univ Manchester, Inst Canc Studies, Christie Hosp, Dept Med Oncol, Manchester, Lancs, England. [Delle Fave, G.] Univ Roma La Sapienza, Azienda Osped St Andrea, Digest & Liver Dis Unit, Rome, Italy. [Van Cutsem, E.] Univ Hosp Gasthuisberg Leuven, Leuven, Belgium. [Van Cutsem, E.] KULeuven, Dept Gastroenterol Digest Oncol, Leuven, Belgium. [Tesselaar, M. E. T.] Nederlands Kanker Inst Antoni van Leeuwenhoek, Dept Internal Oncol & Gastroenterol Hepatol, Amsterdam, Netherlands. [Shimada, Y.] Natl Canc Ctr, Dept Gastrointestinal Med Oncol, Tokyo, Japan. [Oh, D. Y.] Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. [Strosberg, J.] H Lee Moffitt Canc Ctr & Res Inst, Dept Med, Tampa, FL USA. [Kulke, M. H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Pavel, M. E.] Charite Univ Med Berlin, Dept Internal Med Hepatol & Gastroenterol, Berlin, Germany. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2015 VL 51 SU 3 MA 5LBA BP S709 EP S710 PG 3 WC Oncology SC Oncology GA CS2GP UT WOS:000361887403252 ER PT J AU Goverman, J Bittner, EA Friedstat, JS Moore, M Nozari, A Ibrahim, AE Sarhane, KA Chang, PH Sheridan, RL Fagan, SP AF Goverman, Jeremy Bittner, Edward A. Friedstat, Jonathan S. Moore, Molly Nozari, Ala Ibrahim, Amir E. Sarhane, Karim A. Chang, Philip H. Sheridan, Robert L. Fagan, Shawn P. TI Discrepancy in Initial Pediatric Burn Estimates and Its Impact on Fluid Resuscitation SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID SURFACE-AREA; INJURY; EMERGENCY; SIZE; UNIT; MANAGEMENT; PRESSURE; ROOM AB One of the fundamental aspects of initial burn care is the ability to accurately measure the TBSA of injured tissue. Discrepancies between initial estimates of burn size and actual TBSA (determined at the burn unit) have long been reported. These inconsistencies have the potential for unnecessary patient transfer and inappropriate fluid administration which may result in morbidity. In an effort to study these inconsistencies and their impact on initial care, we evaluated the differences between initial TBSA estimates and its impact on fluid resuscitation at an American Burn Association-verified pediatric burn center. A prospective observational study of 50 consecutive burn patients admitted to Shriner's Hospital for Children in Boston, Massachusetts, between October 2011 and April 2012 was performed. Data collected included age, mechanism of burn injury, type of referral center, referring hospital TBSA, and volume of fluid administration as well as admission TBSA and volume of fluid administration. Determination of over or under resuscitation was based on comparing the amount of fluids received at the referral center to that received at the pediatric burn center. A total of 50 patients were admitted during the 7-month study period. The average age was 4.1 years old (25 days-16 years) and the average TBSA was 2.5% (0.25-55%). There were significant differences in the TBSA calculations between referring centers and the pediatric burn center. Overestimation of scald and contact burn size (P < .05) was noted with no difference in flame burn size estimation. Community referrals were more likely than tertiary centers to overestimate TBSA (P < .05 vs P = .29). Overall, 59% of study patients were administered more fluid at the referring hospital than would have been expected by the burn size calculated at our facility. Inconsistencies with the estimation of TBSA burn between referring hospitals and tertiary referral centers remains a problem in pediatric patients and may lead to inappropriate resuscitation. This study highlights the continued need for educational outreach programs and for the provision of novel resources to initial burn providers. Additional support through online resources (eg, Lund-Browder diagram) and remotely assisting providers during their TBSA measurements are potential options which may help to improve the initial care of burn patients. C1 [Goverman, Jeremy; Moore, Molly; Ibrahim, Amir E.; Chang, Philip H.; Sheridan, Robert L.; Fagan, Shawn P.] Massachusetts Gen Hosp, Div Burn Surg, Sumner Redstone Burn Ctr, Boston, MA 02114 USA. [Goverman, Jeremy; Moore, Molly; Ibrahim, Amir E.; Chang, Philip H.; Sheridan, Robert L.; Fagan, Shawn P.] Shriners Hosp Children, Boston, MA USA. [Bittner, Edward A.; Nozari, Ala] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Friedstat, Jonathan S.] Univ N Carolina, Div Plast & Reconstruct Surg, Chapel Hill, NC USA. [Sarhane, Karim A.] Johns Hopkins Univ, Dept Plast & Reconstruct Surg, Sch Med, Baltimore, MD USA. RP Goverman, J (reprint author), Massachusetts Gen Hosp, Div Burns, 55 Fruit St, Boston, MA 02114 USA. EM Jgoverman@partners.org NR 31 TC 5 Z9 5 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1559-047X EI 1559-0488 J9 J BURN CARE RES JI J. Burn Care Res. PD SEP-OCT PY 2015 VL 36 IS 5 BP 574 EP 579 DI 10.1097/BCR.0000000000000185 PG 6 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA CT0PP UT WOS:000362498900007 PM 25407387 ER PT J AU Kiwanuka, JK Ttendo, SS Eromo, E Joseph, SE Duan, ME Haastrup, AA Baker, K Firth, PG AF Kiwanuka, J. K. Ttendo, S. S. Eromo, E. Joseph, S. E. Duan, M. E. Haastrup, A. A. Baker, K. Firth, P. G. TI Synchronous distance anesthesia education by Internet videoconference between Uganda and the United States SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE Anesthesia; Distance education; Global health; Internet ID SUB-SAHARAN AFRICA; HEALTH-PROFESSIONALS; METAANALYSIS; MORTALITY; RESIDENCY; MEDICINE; SYSTEMS; REDUCE; CARE AB Study objective: We evaluated the effectiveness of anesthesia education delivered via Internet videoconferencing between the Massachusetts General Hospital, Boston, MA, and Mbarara Regional Referral Hospital, Uganda. Design: This is a prospective educational study. Setting: The setting is the education in 2 hospitals in Uganda and the United States. Subjects: The subjects are anesthesia residents. Interventions: The interventions are anesthesia education lectures delivered in person and via Internet videoconferencing. Measurements: The average pre-lecture and post-lecture scores of the local, remote, and combined audiences were compared. Main results: Post-lecture test scores improved over pre-lecture scores: local audience, 59%+/- 22% to 81%+/- 16%, P=.0002, g=1.144; remote audience, 51%+/- 19% to 81%+/- 8%, P<.0001, g=2.058; and combined scores, 56%+/- 14% to 82%+/- 8%, P<.0001, g=2.069). Conclusions: Transfer of anesthetic knowledge occurs via small group lectures delivered both in person and remotely via synchronous Internet videoconferencing. This technique may be useful to expand educational capacity and international cooperation between academic institutions, a particular priority in the growing field of global health. (C) 2015 Elsevier Inc. All rights reserved. C1 [Kiwanuka, J. K.; Ttendo, S. S.] Mbarara Univ Sci & Technol, Mbarara Reg Referral Hosp, Dept Anaesthesia & Crit Care, Mbarara, Uganda. [Eromo, E.; Joseph, S. E.; Duan, M. E.; Haastrup, A. A.; Baker, K.; Firth, P. G.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Firth, PG (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM pfirth@partners.org FU Massachusetts General Hospital Center for Global Health (Boston, MA) FX Funding was received from the Massachusetts General Hospital Center for Global Health (Boston, MA). The authors have no competing interests. NR 24 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 EI 1873-4529 J9 J CLIN ANESTH JI J. Clin. Anesth. PD SEP PY 2015 VL 27 IS 6 BP 499 EP 503 DI 10.1016/j.jclinane.2015.04.004 PG 5 WC Anesthesiology SC Anesthesiology GA CS9CM UT WOS:000362386700010 PM 26001319 ER PT J AU Leung, Y Vacanti, FX AF Leung, Yiuka Vacanti, Francis X. TI Awake without complaints: maximizing comfort during awake fiberoptic intubation SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE Awake fiberoptic intubation; Local; Topical anesthesia; Upper airway; Anesthestics ID PATIENT AB In obese patients with unfavorable airways, awake fiberoptic intubations are sometimes performed to maintain spontaneous respiration and airway reflexes, until a secure airway is attained. Obese patients may be sensitive to the effects of sedation. Rapid oxygen desaturation may occur as a result of brief moments of apnea from even minimal amounts of sedating medications, due to poor baseline functional reserve as well as common comorbid conditions such as obstructive sleep apnea and obesity hypoventilation syndrome. To maximize the chance of success when performing an awake fiberoptic intubation in a minimally sedated patient, the upper airway should be sufficiently anesthetized. Adequate topical anesthesia minimizes airway stimulation, optimizes patient comfort and facilitates patient compliance. We report two cases of awake fiberoptic intubation in two morbidly obese patients, where a simple apparatus, made of an atomizer embedded in an oral airway, was used to effectively topicalize the airway and achieve excellent intubating condition with minimal sedation. (C) 2015 Elsevier Inc. All rights reserved. C1 [Leung, Yiuka; Vacanti, Francis X.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02144 USA. RP Leung, Y (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02144 USA. EM yleung1@partners.org; fvacanti@mgh.harvard.edu NR 6 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 EI 1873-4529 J9 J CLIN ANESTH JI J. Clin. Anesth. PD SEP PY 2015 VL 27 IS 6 BP 517 EP 519 DI 10.1016/j.jclinane.2015.05.004 PG 3 WC Anesthesiology SC Anesthesiology GA CS9CM UT WOS:000362386700014 PM 26093943 ER PT J AU Buchbinder, E Hodi, FS AF Buchbinder, Elizabeth Hodi, F. Stephen TI Cytotoxic T lymphocyte antigen-4 and immune checkpoint blockade SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Review ID PRETREATED ADVANCED MELANOMA; RANDOMIZED CLINICAL-TRIAL; METASTATIC MELANOMA; CTLA-4 BLOCKADE; PHASE-II; ANTI-CTLA-4 ANTIBODIES; PROSTATE-CANCER; DOUBLE-BLIND; TUMOR MICROENVIRONMENT; ANTITUMOR-ACTIVITY AB The relationship between cancer and the immune system is complex and provides unique therapeutic opportunities. Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a regulatory molecule that suppresses T cell effector function following initial activation by costimulatory signals. Fully human monoclonal antibodies targeting CTLA-4 have been shown to increase T cell function and antitumor responses in patients with advanced metastatic melanoma. Responses observed with such immune checkpoint therapy can follow a different pattern from that seen with cytotoxic chemotherapy or targeted therapy and may continue after therapy is discontinued. In addition, the toxicities that are associated with anti-CTLA-4 therapy may differ from those of conventional therapies and consist of inflammatory events in parts of the body that do not contain cancerous cells. Early recognition of these inflammatory events and intervention is important, and the identification of predictive biomarlcers continues to be an unfulfilled need in the field of immunotherapy. Combinatorial approaches with targeted therapies, radiation therapy, chemotherapy, or other immune checkpoint agonists/antagonists have the potential to increase the efficacy of CTLA-4 blockade. C1 [Buchbinder, Elizabeth; Hodi, F. Stephen] Dana Farber Canc Inst, Melanoma Dis Ctr, Dept Med Oncol, Boston, MA 02215 USA. RP Buchbinder, E (reprint author), Dana Farber Canc Inst, Melanoma Dis Ctr, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM Elizabeth_buchbinder@dfci.harvard.edu FU Bristol-Myers Squibb; Merck; Pfizer; Genentech FX The authors received research support from Bristol-Myers Squibb, Merck, Pfizer, and Genentech. NR 87 TC 17 Z9 17 U1 1 U2 8 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2015 VL 125 IS 9 BP 3377 EP 3383 DI 10.1172/JCI80012 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CS7YT UT WOS:000362303600012 PM 26325034 ER PT J AU Roy, A Al-Qusairi, L Donnelly, BF Ronzaud, C Marciszyn, AL Gong, F Chang, YPC Butterworth, MB Pastor-Soler, NM Hallows, KR Staub, O Subramanya, AR AF Roy, Ankita Al-Qusairi, Lama Donnelly, Bridget F. Ronzaud, Caroline Marciszyn, Allison L. Gong, Fan Chang, Y. P. Christy Butterworth, Michael B. Pastor-Soler, Nuria M. Hallows, Kenneth R. Staub, Olivier Subramanya, Arohan R. TI Alternatively spliced praline-rich cassettes link WNK1 to aldosterone action SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NA+-CL-COTRANSPORTER; SODIUM-CHLORIDE COTRANSPORTER; DISTAL CONVOLUTED TUBULE; KINASE-DEFECTIVE ISOFORM; PROTEIN-KINASE; BLOOD-PRESSURE; PHOSPHORYLATION SITES; SIGNALING PATHWAY; LIDDLES-SYNDROME; SALT TRANSPORT AB The thiazide-sensitive NaCl cotransporter (NCC) is important for renal salt handling and blood-pressure homeostasis. The canonical NCC-activating pathway consists of With-No-Lysine (WNK) kinases and their downstream effector kinases SPAK and OSR1, which phosphorylate NCC directly. The upstream mechanisms that connect physiological stimuli to this system remain obscure. Here, we have shown that aldosterone activates SPAK/OSR1 via WNk1. We identified 2 alternatively spliced exons embedded within a proline-rich region of WNK1 that contain PV motifs, which bind the E3 ubiquitin ligase NEDD4-2. PV motif-containing WNK1 isoforms were expressed in human kidney, and these isoforms were efficiently degraded by the ubiquitin proteasome system, an effect reversed by the aldosterone-induced kinase SGK1. In gene-edited cells, WNK1 deficiency negated regulatory effects of NEDD4-2 and SGK1 on NCC, suggesting that WNK1 mediates aldosterone-dependent activity of the WNK/SPAK/OSR1 pathway. Aldosterone infusion increased proline-rich WNK1 isoforrn abundance in WT mice but did not alter WNK1 abundance in hypertensive Nedd4-2 KO mice, which exhibit high baseline WNK1 and SPAK/OSR1 activity toward NCC. Conversely, hypotensive Sgk1 KO mice exhibited low WNK1 expression and activity. Together, our findings indicate that the proline-rich exons are modular cassettes that convert WNK1 into a NEDD4-2 substrate, thereby linking aldosterone and other NEDD4-2-suppressing antinatriuretic hormones to NCC phosphorylation status. C1 [Roy, Ankita; Donnelly, Bridget F.; Marciszyn, Allison L.; Gong, Fan; Pastor-Soler, Nuria M.; Hallows, Kenneth R.; Subramanya, Arohan R.] Univ Pittsburgh, Dept Med, Sch Med, Pittsburgh, PA 15261 USA. [Al-Qusairi, Lama; Ronzaud, Caroline; Staub, Olivier] Univ Lausanne, Dept Pharmacol & Toxicol, Lausanne, Switzerland. [Chang, Y. P. Christy] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Butterworth, Michael B.; Pastor-Soler, Nuria M.; Hallows, Kenneth R.; Subramanya, Arohan R.] Univ Pittsburgh, Sch Med, Dept Cell Biol, Pittsburgh, PA 15261 USA. [Subramanya, Arohan R.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Subramanya, AR (reprint author), Univ Pittsburgh, Dept Med, Sch Med, Renal Electrolyte Div, S828A Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM ars129@pitt.edu FU NIH [R01DK098145, R01DK84184, R01DK75048, R00DK78917, R01HL88120, P30DK79307]; American Society of Nephrology Gottschalk Scholar grant; Swiss National Science Foundation [310030_0141013]; Swiss National Centre of Competence in Research Kidney Control of Homeostasis (NCCR Kidney.CH); U.S. Department of Veterans Affairs; VA VISN4 Competitive Pilot Project Funds; James A. Shaver Fund of the American Heart Association [10BGIA3890010] FX This work was supported, in whole or in part, by NIH grants R01DK098145 (to A.R. Subramanya), R01DK84184 (to N.M. Pastor-Soler), R01DK75048 (to K.R. Hallows), R00DK78917 (to M.B. Butterworth), R01HL88120 (to Y.P.C. Chang), and P30DK79307 (to the Pittsburgh Center for Kidney Research), as well as an American Society of Nephrology Gottschalk Scholar grant (to M.B. Butterworth), Swiss National Science Foundation grant 310030_0141013 (to O. Staub), the Swiss National Centre of Competence in Research Kidney Control of Homeostasis (NCCR Kidney.CH) grant (to O. Staub), a Mid-Level Career Development Award from the U.S. Department of Veterans Affairs (to A.R. Subramanya), VA VISN4 Competitive Pilot Project Funds (to A.R. Subramanya), and grant 10BGIA3890010 from the James A. Shaver Fund of the American Heart Association (to A.R. Subramanya). We thank David Ellison and Jim Wade for NCC antibodies; Alan Pao for constructs; Alexandra Socovich, Sean Khadem, Avin C. Snyder, and Xiaoning Liu for technical assistance; and Vivek Bhalla and Rodrigo Alzamora for helpful discussions. NR 67 TC 11 Z9 11 U1 2 U2 5 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2015 VL 125 IS 9 BP 3433 EP 3448 DI 10.1172/JCI75245 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CS7YT UT WOS:000362303600021 PM 26241057 ER PT J AU Mihatov, N Dudzinski, DM AF Mihatov, Nino Dudzinski, David M. TI Intraaortic Balloon Pump Rupture SO JOURNAL OF INVASIVE CARDIOLOGY LA English DT Editorial Material DE intraaortic balloon pump; complications; percutaneous coronary intervention AB Intraaortic balloon pump ( IABP) rupture is a rare complication, with overall reported incidence of 1%. It is thought to be related to abrasion of balloon material against atherosclerotic plaques during or after placement. The presented case demonstrates the presence of blood within the IABP driveline, which is a key indicator of rupture. C1 [Mihatov, Nino] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. [Dudzinski, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Cardiol, Boston, MA 02114 USA. [Dudzinski, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, DepEchocardiog, Boston, MA 02114 USA. [Dudzinski, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Crit Care, Boston, MA 02114 USA. RP Mihatov, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,GRB 740, Boston, MA 02114 USA. EM nmihatov@partners.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1042-3931 EI 1557-2501 J9 J INVASIVE CARDIOL JI J. Invasive Cardiol. PD SEP PY 2015 VL 27 IS 9 BP E203 EP E203 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CT2SG UT WOS:000362653400006 PM 26332886 ER PT J AU Piel, J AF Piel, Jennifer TI The Defense of Involuntary Intoxication by Prescribed Medications: An Appellate Case Review SO JOURNAL OF THE AMERICAN ACADEMY OF PSYCHIATRY AND THE LAW LA English DT Review AB The defense of involuntary intoxication has long been an exception to the general notion that intoxication is not a defense to criminal liability. The consumption of medications prescribed by a physician can form the basis of an involuntary-intoxication defense. In this article, I review cases where defendants relied on the use of prescribed medications for an involuntary-intoxication defense. The medications most frequently implicated by defendants are listed by name and by class. From the case law, I provide a summary of the defense and a review of the pitfalls of the defense to serve as practice pointers for forensic evaluators. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Piel, J (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM jennifer.piel@va.gov NR 10 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD PSYCHIATRY & LAW PI BLOOMFIELD PA ONE REGENCY DR, PO BOX 30, BLOOMFIELD, CT 06002 USA SN 1093-6793 EI 1943-3662 J9 J AM ACAD PSYCHIATRY JI J. Am. Acad. Psychiatry Law PD SEP 1 PY 2015 VL 43 IS 3 BP 321 EP 328 PG 8 WC Law; Psychiatry SC Government & Law; Psychiatry GA CS9VX UT WOS:000362442100010 PM 26438810 ER PT J AU Piel, J AF Piel, Jennifer TI Expanding Slayer Statutes to Elder Abuse SO JOURNAL OF THE AMERICAN ACADEMY OF PSYCHIATRY AND THE LAW LA English DT Editorial Material AB Common law has a dictum that people must not benefit from their crimes. In years past, states have enacted slayer rules to prevent killers from inheriting from their victims. The specific criteria and applicability of slayer rules vary by jurisdiction. Recently, several states, including Washington, have expanded their slayer rules to disqualify persons from inheriting if they have been involved in abuse or financial exploitation of the deceased. Reviewed herein are the abuse disinheritance laws, the relationship of the laws to concepts of testamentary capacity and undue influence, and the relevance to forensic psychiatric evaluations. C1 [Piel, Jennifer] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Piel, Jennifer] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Piel, J (reprint author), VA Puget Sound Hlth Care Syst, 1660 South Columbian Way,MS 116 MHC, Seattle, WA 98108 USA. EM jennifer.piel@va.gov NR 5 TC 0 Z9 0 U1 0 U2 1 PU AMER ACAD PSYCHIATRY & LAW PI BLOOMFIELD PA ONE REGENCY DR, PO BOX 30, BLOOMFIELD, CT 06002 USA SN 1093-6793 EI 1943-3662 J9 J AM ACAD PSYCHIATRY JI J. Am. Acad. Psychiatry Law PD SEP 1 PY 2015 VL 43 IS 3 BP 369 EP 376 PG 8 WC Law; Psychiatry SC Government & Law; Psychiatry GA CS9VX UT WOS:000362442100015 PM 26438815 ER PT J AU Ramanathan, DS Gulati, T Ganguly, K AF Ramanathan, Dhakshin S. Gulati, Tanuj Ganguly, Karunesh TI Sleep-Dependent Reactivation of Ensembles in Motor Cortex Promotes Skill Consolidation SO PLOS BIOLOGY LA English DT Article ID SLOW-WAVE SLEEP; FOREBRAIN CHOLINERGIC SYSTEM; MEMORY CONSOLIDATION; PREFRONTAL CORTEX; CORTICOSTRIATAL PLASTICITY; CORTICAL PLASTICITY; DENDRITIC SPINES; BRAIN PLASTICITY; TIME-COURSE; IN-VIVO AB Despite many prior studies demonstrating offline behavioral gains in motor skills after sleep, the underlying neural mechanisms remain poorly understood. To investigate the neurophysiological basis for offline gains, we performed single-unit recordings in motor cortex as rats learned a skilled upper-limb task. We found that sleep improved movement speed with preservation of accuracy. These offline improvements were linked to both replay of task-related ensembles during non-rapid eye movement (NREM) sleep and temporal shifts that more tightly bound motor cortical ensembles to movements; such offline gains and temporal shifts were not evident with sleep restriction. Interestingly, replay was linked to the coincidence of slow-wave events and bursts of spindle activity. Neurons that experienced the most consistent replay also underwent the most significant temporal shift and binding to the motor task. Significantly, replay and the associated performance gains after sleep only occurred when animals first learned the skill; continued practice during later stages of learning (i.e., after motor kinematics had stabilized) did not show evidence of replay. Our results highlight how replay of synchronous neural activity during sleep mediates large-scale neural plasticity and stabilizes kinematics during early motor learning. C1 [Ramanathan, Dhakshin S.; Gulati, Tanuj; Ganguly, Karunesh] San Francisco VA Med Ctr, Neurol & Rehabil Serv, San Francisco, CA 94121 USA. [Ramanathan, Dhakshin S.] San Francisco VA Med Ctr, Psychiat Serv, San Francisco, CA USA. [Ramanathan, Dhakshin S.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Gulati, Tanuj; Ganguly, Karunesh] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. RP Ganguly, K (reprint author), San Francisco VA Med Ctr, Neurol & Rehabil Serv, San Francisco, CA 94121 USA. EM karunesh.ganguly@ucsf.edu FU Department of Veterans Affairs, Veterans Health Administration [CDA B6674W]; American Heart Association; Northern California Institute for Research and Education (NCIRE); start-up funds from UCSF Department of Neurology; Burroughs Wellcome Fund FX This work was supported by fellowship awards from the Department of Veterans Affairs, Veterans Health Administration (http://www.va.gov/) to DSR and from the American Heart Association (http://www.heart.org/HEARTORG/) to TG. This work was also supported by awards to KG from the Department of Veterans Affairs, Veterans Health Administration (http://www.va.gov/, CDA B6674W); from the Northern California Institute for Research and Education (NCIRE, www.ncire.org) and start-up funds from the UCSF Department of Neurology (http://neurology.ucsf.edu). KG also holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund (http://www.bwfund.org/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 79 TC 10 Z9 10 U1 2 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1545-7885 J9 PLOS BIOL JI PLoS. Biol. PD SEP PY 2015 VL 13 IS 9 AR e1002263 DI 10.1371/journal.pbio.1002263 PG 25 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA CS7LW UT WOS:000362266100025 PM 26382320 ER PT J AU Foo, J Liu, LL Leder, K Riester, M Iwasa, Y Lengauer, C Michor, F AF Foo, Jasmine Liu, Lin L. Leder, Kevin Riester, Markus Iwasa, Yoh Lengauer, Christoph Michor, Franziska TI An Evolutionary Approach for Identifying Driver Mutations in Colorectal Cancer SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID PASSENGER MUTATIONS; BREAST-CANCER; GENES; TUMOR; IDENTIFICATION; PROGRESSION; METASTASIS; LANDSCAPES; DISCOVERY; PATHWAYS AB The traditional view of cancer as a genetic disease that can successfully be treated with drugs targeting mutant onco-proteins has motivated whole-genome sequencing efforts in many human cancer types. However, only a subset of mutations found within the genomic landscape of cancer is likely to provide a fitness advantage to the cell. Distinguishing such "driver" mutations from innocuous "passenger" events is critical for prioritizing the validation of candidate mutations in disease-relevant models. We design a novel statistical index, called the Hitchhiking Index, which reflects the probability that any observed candidate gene is a passenger alteration, given the frequency of alterations in a cross-sectional cancer sample set, and apply it to a mutational data set in colorectal cancer. Our methodology is based upon a population dynamics model of mutation accumulation and selection in colorectal tissue prior to cancer initiation as well as during tumorigenesis. This methodology can be used to aid in the prioritization of candidate mutations for functional validation and contributes to the process of drug discovery. C1 [Foo, Jasmine] Univ Minnesota Twin Cities, Dept Math, St Paul, MN 55455 USA. [Liu, Lin L.; Riester, Markus; Michor, Franziska] Harvard Univ, TH Chan Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Liu, Lin L.; Riester, Markus; Michor, Franziska] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Leder, Kevin] Univ Minnesota Twin Cities, Ind & Syst Engn, St Paul, MN USA. [Iwasa, Yoh] Kyushu Univ, Dept Biol, Fukuoka 812, Japan. [Lengauer, Christoph] Blueprint Med, Cambridge, MA USA. RP Foo, J (reprint author), Univ Minnesota Twin Cities, Dept Math, St Paul, MN 55455 USA. EM michor@jimmy.harvard.edu RI Iwasa, Yoh/G-5368-2010 OI Iwasa, Yoh/0000-0003-0691-1852 FU Dana-Farber Cancer Institute Physical Sciences Oncology Center FX The authors gratefully acknowledge support from the Dana-Farber Cancer Institute Physical Sciences Oncology Center. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 8 Z9 8 U1 1 U2 14 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 SEP PY 2015 VL 11 IS 9 AR e1004350 DI 10.1371/journal.pcbi.1004350 PG 19 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA CS7LZ UT WOS:000362266400006 PM 26379039 ER PT J AU Zhang, NQ Wang, HY Fang, Y Wang, J Zheng, XQ Liu, XS AF Zhang, Naiqian Wang, Haiyun Fang, Yun Wang, Jun Zheng, Xiaoqi Liu, X. Shirley TI Predicting Anticancer Drug Responses Using a Dual-Layer Integrated Cell Line-Drug Network Model SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID PRECISION MEDICINE; SENSITIVITY; CANCER; IDENTIFICATION; SIGNATURE; PANEL AB The ability to predict the response of a cancer patient to a therapeutic agent is a major goal in modern oncology that should ultimately lead to personalized treatment. Existing approaches to predicting drug sensitivity rely primarily on profiling of cancer cell line panels that have been treated with different drugs and selecting genomic or functional genomic features to regress or classify the drug response. Here, we propose a dual-layer integrated cell line-drug network model, which uses both cell line similarity network (CSN) data and drug similarity network (DSN) data to predict the drug response of a given cell line using a weighted model. Using the Cancer Cell Line Encyclopedia (CCLE) and Cancer Genome Project (CGP) studies as benchmark datasets, our single-layer model with CSN or DSN and only a single parameter achieved a prediction performance comparable to the previously generated elastic net model. When using the dual-layer model integrating both CSN and DSN, our predicted response reached a 0.6 Pearson correlation coefficient with observed responses for most drugs, which is significantly better than the previous results using the elastic net model. We have also applied the dual-layer cell line-drug integrated network model to fill in the missing drug response values in the CGP dataset. Even though the dual-layer integrated cell line-drug network model does not specifically model mutation information, it correctly predicted that BRAF mutant cell lines would be more sensitive than BRAF wild-type cell lines to three MEK1/2 inhibitors tested. C1 [Zhang, Naiqian; Fang, Yun; Wang, Jun; Zheng, Xiaoqi] Shanghai Normal Univ, Dept Math, Shanghai, Peoples R China. [Wang, Haiyun] Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China. [Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Liu, X. Shirley] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02115 USA. RP Zhang, NQ (reprint author), Shanghai Normal Univ, Dept Math, Shanghai, Peoples R China. EM jwang@shnu.edu.cn; xqzheng@shnu.edu.cn; xsliu@jimmy.harvard.edu FU National Natural Science Foundations of China [31100912, 11201306, 61572327, 31329003]; Innovation Program of Shanghai Municipal Education Commission [13YZ065]; United States National Institutes of Health [GM099409] FX This work was funded by the National Natural Science Foundations of China (No. 31100912 to HW; 11201306 to YF; 61572327 to XZ; 31329003 to XSL), the Innovation Program of Shanghai Municipal Education Commission (13YZ065 to YF), and the United States National Institutes of Health (GM099409 to XSL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 6 Z9 6 U1 2 U2 8 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 SEP PY 2015 VL 11 IS 9 AR e1004498 DI 10.1371/journal.pcbi.1004498 PG 18 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA CS7LZ UT WOS:000362266400040 PM 26418249 ER PT J AU Bajpai, S Kambadakone, A Guimaraes, AR Arellano, RS Gervais, DA Sahani, D AF Bajpai, Surabhi Kambadakone, Avinash Guimaraes, Alexander R. Arellano, Ronald S. Gervais, Debra A. Sahani, Dushyant TI Image-guided Treatment in the Hepatobiliary System: Role of Imaging in Treatment Planning and Posttreatment Evaluation SO RADIOGRAPHICS LA English DT Article ID PERCUTANEOUS RADIOFREQUENCY ABLATION; HEPATOCELLULAR-CARCINOMA RESPONSE; RADIOLOGY POSITION STATEMENT; SECONDARY LIVER MALIGNANCIES; ENERGY COMPUTED-TOMOGRAPHY; DIFFUSION-WEIGHTED MRI; OF-THE-LITERATURE; TRANSARTERIAL CHEMOEMBOLIZATION; INTERVENTIONAL RADIOLOGY; Y-90 RADIOEMBOLIZATION AB In the past decade, image-guided targeted treatments such as percutaneous ablation, intra-arterial embolic therapies, and targeted radiation therapy have shown substantial promise in management of hepatobiliary malignancies. Imaging is integral to patient selection, treatment delivery, and assessment of treatment effectiveness. Preprocedural imaging is crucial and allows local tumor staging, evaluation of surrounding structures, and selection of suitable therapeutic options and strategies for treatment delivery. Postprocedural imaging is required to monitor therapeutic success, detect residual or recurrent disease, and identify procedure-related complications to guide appropriate future therapy. Technical innovations in cross-sectional imaging techniques such as computed tomography (CT) and magnetic resonance (MR) imaging, combined with advances in image postprocessing and new types of contrast agents, allow precise morphologic assessment and functional evaluation of hepatobiliary tumors. Advanced postprocessing techniques such as image fusion and volumetric assessment not only facilitate procedural planning and treatment delivery but also enhance post-treatment imaging surveillance. In addition, molecular imaging techniques such as fluorodeoxyglucose positron emission tomography (PET), PET/CT, and PET/MR imaging offer opportunities to evaluate various physiologic properties of tumors. (C) RSNA, 2015 C1 [Bajpai, Surabhi; Kambadakone, Avinash; Guimaraes, Alexander R.; Arellano, Ronald S.; Gervais, Debra A.; Sahani, Dushyant] Massachusetts Gen Hosp, Div Abdominal Imaging, Boston, MA 02114 USA. RP Sahani, D (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@mgh.harvard.edu NR 77 TC 1 Z9 1 U1 2 U2 2 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 SEP-OCT PY 2015 VL 35 IS 5 BP 1393 EP 1418 DI 10.1148/rg.2015140281 PG 26 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CT0SZ UT WOS:000362508400007 PM 26252365 ER PT J AU Huang, SY Seethamraju, RT Patel, P Hahn, PF Kirsch, JE Guimaraes, AR AF Huang, Susie Y. Seethamraju, Ravi T. Patel, Pritesh Hahn, Peter F. Kirsch, John E. Guimaraes, Alexander R. TI Body MR Imaging: Artifacts, k-Space, and Solutions SO RADIOGRAPHICS LA English DT Article ID SPIN-ECHO; PRINCIPLES; REDUCTION; SENSE; COILS AB Body magnetic resonance (MR) imaging is challenging because of the complex interaction of multiple factors, including motion arising from respiration and bowel peristalsis, susceptibility effects secondary to bowel gas, and the need to cover a large field of view. The combination of these factors makes body MR imaging more prone to artifacts, compared with imaging of other anatomic regions. Understanding the basic MR physics underlying artifacts is crucial to recognizing the trade-offs involved in mitigating artifacts and improving image quality. Artifacts can be classified into three main groups: (a) artifacts related to magnetic field imperfections, including the static magnetic field, the radiofrequency (RF) field, and gradient fields; (b) artifacts related to motion; and (c) artifacts arising from methods used to sample the MR signal. Static magnetic field homogeneity is essential for many MR techniques, such as fat saturation and balanced steady-state free precession. Susceptibility effects become more pronounced at higher field strengths and can be ameliorated by using spin-echo sequences when possible, increasing the receiver bandwidth, and aligning the phase-encoding gradient with the strongest susceptibility gradients, among other strategies. Nonuniformities in the RF transmit field, including dielectric effects, can be minimized by applying dielectric pads or imaging at lower field strength. Motion artifacts can be overcome through respiratory synchronization, alternative k-space sampling schemes, and parallel imaging. Aliasing and truncation artifacts derive from limitations in digital sampling of the MR signal and can be rectified by adjusting the sampling parameters. Understanding the causes of artifacts and their possible solutions will enable practitioners of body MR imaging to meet the challenges of novel pulse sequence design, parallel imaging, and increasing field strength. (C) RSNA, 2015 C1 [Huang, Susie Y.; Hahn, Peter F.; Guimaraes, Alexander R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Huang, Susie Y.; Guimaraes, Alexander R.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Boston, MA 02114 USA. [Patel, Pritesh] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [Seethamraju, Ravi T.; Kirsch, John E.] Siemens Healthcare USA, Malvern, PA USA. RP Huang, SY (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM syhuang@nmr.mgh.harvard.edu FU National Institutes of Health [K08EB012859] FX The work was supported by the National Institutes of Health [grant number K08EB012859]. NR 26 TC 3 Z9 3 U1 2 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 SEP-OCT PY 2015 VL 35 IS 5 BP 1439 EP 1460 DI 10.1148/rg.2015140289 PG 22 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CT0SZ UT WOS:000362508400011 PM 26207581 ER PT J AU Pugmire, BS Lim, R Avery, LL AF Pugmire, Brian S. Lim, Ruth Avery, Laura L. TI Review of Ingested and Aspirated Foreign Bodies in Children and Their Clinical Significance for Radiologists SO RADIOGRAPHICS LA English DT Article ID UPPER GASTROINTESTINAL-TRACT; MANAGEMENT; GLASS; WILL AB Ingested and aspirated foreign bodies are a common occurrence in children and are important causes of morbidity and mortality in the pediatric population. Imaging plays an important role in the diagnosis of ingested and aspirated foreign bodies in children and can be crucial to guiding the clinical management of these patients. Prompt identification and localization of ingested foreign bodies is essential to determining the appropriate treatment, as several types of commonly ingested foreign bodies require urgent removal and others can be managed conservatively. In particular, disk batteries impacted in the esophagus carry a high risk of esophageal injury or perforation; multiple ingested magnets can become attracted to each other across bowel walls and cause bowel perforation and fistula formation; and sharp objects commonly cause complications as they pass through the gastrointestinal tract. Accordingly, these ingested foreign bodies warrant aggressive clinical management and therefore radiologists must be familiar with their imaging appearances and clinical implications. Prompt recognition of secondary radiographic signs of foreign-body aspiration is also crucial, as clinical symptoms can sometimes be nonspecific and most aspirated foreign bodies are radiolucent. Overall, radiography is the most important modality in the evaluation of ingested or aspirated foreign bodies; however, fluoroscopy and computed tomography play an ancillary role in complicated cases. It is essential that every radiologist who interprets imaging examinations of children be aware of the imaging appearances of commonly ingested and aspirated foreign bodies and their clinical significance. (C) RSNA, 2015 C1 [Pugmire, Brian S.] Cincinnati Childrens Hosp Med Ctr, Dept Radiol, Cincinnati, OH 45229 USA. [Lim, Ruth; Avery, Laura L.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Pugmire, BS (reprint author), Cincinnati Childrens Hosp Med Ctr, Dept Radiol, 3333 Burnet Ave, Cincinnati, OH 45229 USA. EM Brian.Pugmire@cchmc.org NR 27 TC 0 Z9 0 U1 1 U2 1 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 SEP-OCT PY 2015 VL 35 IS 5 BP 1528 EP 1538 DI 10.1148/rg.2015140287 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CT0SZ UT WOS:000362508400016 PM 26295734 ER PT J AU Eisele, SC Dietrich, J AF Eisele, Sylvia C. Dietrich, Joerg TI Cerebral radiation necrosis: diagnostic challenge and clinical management SO REVISTA DE NEUROLOGIA LA Spanish DT Review DE Bevacizumab; Complications; Glioma; Management; Radiation necrosis; Review; Steroids ID CENTRAL-NERVOUS-SYSTEM; MAGNETIC-RESONANCE-SPECTROSCOPY; INTERSTITIAL THERMAL THERAPY; STEREOTACTIC RADIOSURGERY; BRAIN METASTASES; TUMOR RECURRENCE; NASOPHARYNGEAL CARCINOMA; DIFFERENTIATING RECURRENT; C-11-METHIONINE PET; PSEUDO-PROGRESSION AB Cerebral radiation is an indispensable cornerstone in the treatment of many primary and metastatic brain tumors. However, besides its desired therapeutic effect on tumor cells, a significant proportion of patients will experience neurotoxic side effects as the consequence of radiotherapy. Radiation necrosis can result in progressive neurological symptoms and radiographic changes. To differentiate radiation necrosis from progressive tumor based on imaging can pose a diagnostic challenge because the MRI characteristics may be similar in both situations. Therefore, surgical biopsy and pathological confirmation is sometimes necessary to guide further management. Effective treatment options for cerebral radiation necrosis exist and should be offered to symptomatic patients. A better understanding of the cellular and molecular processes underlying the development of radiation necrosis is necessary to prevent and minimize radiation-associated morbidity and to improve treatment strategies. C1 [Eisele, Sylvia C.; Dietrich, Joerg] Massachusetts Gen Hosp, Serv Neurol, Unidad Neurooncol, Boston, MA 02114 USA. RP Dietrich, J (reprint author), Massachusetts Gen Hosp, Dept Neurol, Div Neurooncol, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM dietrich.jorg@mgh.harvard.edu NR 66 TC 3 Z9 3 U1 3 U2 4 PU REVISTA DE NEUROLOGIA PI BARCELONA PA C/O CESAR VIGUERA, EDITOR, APDO 94121, 08080 BARCELONA, SPAIN SN 0210-0010 EI 1576-6578 J9 REV NEUROLOGIA JI Rev. Neurologia PD SEP 1 PY 2015 VL 61 IS 5 BP 225 EP 232 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA CS7OP UT WOS:000362273400005 PM 26308844 ER PT J AU Edwards, AL Wachter, F Lammert, M Huhn, AJ Luccarelli, J Bird, GH Walensky, LD AF Edwards, Amanda L. Wachter, Franziska Lammert, Margaret Huhn, Annissa J. Luccarelli, James Bird, Gregory H. Walensky, Loren D. TI Cellular Uptake and Ultrastructural Localization Underlie the Proapoptotic Activity of a Hydrocarbon-stapled BIM BH3 Peptide SO ACS CHEMICAL BIOLOGY LA English DT Article ID PROTEIN-PROTEIN INTERACTIONS; STABILIZED ALPHA-HELICES; BCL-2 DOMAINS; REAL-TIME; BAX; ACTIVATION; APOPTOSIS; INHIBITION; AFFINITY; BIMSAHB AB Hydrocarbon stapling has been applied to restore and stabilize the alpha-helical structure of bioactive peptides for biochemical, structural, cellular, and in vivo studies. The peptide sequence, in addition to the composition and location of the installed staple, can dramatically influence the properties of stapled peptides. As a result, constructs that appear similar can have distinct functions and utilities. Here, we perform a side-by-side comparison of stapled peptides modeled after the pro-apoptotic BIM BH3 helix to highlight these principles. We confirm that replacing a salt-bridge with an i, i + 4 hydrocarbon staple does not impair target binding affinity and instead can yield a biologically and pharmacologically enhanced alpha-helical peptide ligand. Importantly, we demonstrate by electron microscopy that the pro-apoptotic activity of a stapled BIM BH3 helix correlates uptake without membrane disruption and accumulate at the organellar site of mechanistic with its activity. capacity to achieve cellular C1 [Edwards, Amanda L.; Wachter, Franziska; Lammert, Margaret; Huhn, Annissa J.; Luccarelli, James; Bird, Gregory H.; Walensky, Loren D.] Dana Farber Canc Inst, Dept Pediat Oncol, Linde Program Canc Chem Biol, Boston, MA 02215 USA. [Walensky, Loren D.] Harvard Univ, Boston Childrens Hosp, Div Hematol Oncol, Sch Med, Boston, MA 02215 USA. RP Walensky, LD (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Linde Program Canc Chem Biol, Boston, MA 02215 USA. EM loren_walensky@dfci.harvard.edu FU NIH [2R01CA050239]; Leukemia and Lymphoma Society (LLS) Marshall A. Lichtman Specialized Center of Research project grant; LLS Scholar Award; National Science Foundation Predoctoral Fellowship; Alexander von Humboldt Foundation Feodor Lynen Fellowship; NIH training grant [T32GM007753] FX We thank E. Smith for graphics and editorial assistance, M. Ericsson for electron microscopy technical support, and M. Godes for assistance with tissue culture. This research was support by NIH grant 2R01CA050239, a Leukemia and Lymphoma Society (LLS) Marshall A. Lichtman Specialized Center of Research project grant, and an LLS Scholar Award to L.D.W., a National Science Foundation Predoctoral Fellowship to A.L.E., and an Alexander von Humboldt Foundation Feodor Lynen Fellowship to F.W. J.L. is supported by NIH training grant T32GM007753. NR 35 TC 6 Z9 6 U1 3 U2 18 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 SEP PY 2015 VL 10 IS 9 BP 2149 EP 2157 DI 10.1021/acschembio.5b00214 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CS1ZI UT WOS:000361867200022 PM 26151238 ER PT J AU Zhao, QC Yetisen, AK Sabouri, A Yun, SH Butt, H AF Zhao, Qiancheng Yetisen, Ali K. Sabouri, Aydin Yun, Seok Hyun Butt, Haider TI Printable Nanophotonic Devices via Holographic Laser Ablation SO ACS NANO LA English DT Article DE holography; laser interference zone plates; diffraction gratings; lenses ID FRESNEL ZONE PLATES; PHOTONIC NANOSENSOR; SENSORS AB Holography plays a significant role in applications such as data storage, light trapping, security, and biosensors. However, conventional fabrication methods remain time-consuming, costly, and complex, limiting the fabrication of holograms and their extensive use. Here, we demonstrate a single-pulse laser ablation technique to write parallel surface gratings and Fresnel zone plates. We utilized a 6 ns high-energy green laser pulse to form interference patterns to record a surface grating with 820 nm periodicity and asymmetric zone plate holograms on 4.5 nm gold-coated substrates. The holographic recording process was completed within seconds. The optical characteristics of the interference patterns have been computationally modeled, and well-ordered polychromatic diffraction was observed from the fabricated holograms. The zone plate showed a significant diffraction angle of 32 degrees from the normal incident for the focal point. The nanosecond laser interference ablation for rapid hologram fabrication holds great potential in a vast range of optical devices. C1 [Zhao, Qiancheng; Sabouri, Aydin; Butt, Haider] Univ Birmingham, Sch Mech Engn, Microengn & Nanotechnol Lab, Birmingham B15 2TT, W Midlands, England. [Yetisen, Ali K.; Yun, Seok Hyun] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Yetisen, Ali K.; Yun, Seok Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Butt, H (reprint author), Univ Birmingham, Sch Mech Engn, Microengn & Nanotechnol Lab, Birmingham B15 2TT, W Midlands, England. EM h.butt@bham.ac.uk OI Butt, Haider/0000-0003-2434-9525 FU Leverhulme Trust FX We thank Piran R. Kidambi for substrates. A.K.Y. and H.B. conceived the idea. A.K.Y. fabricated the gratings. H.B. and A.S. developed all the optical experimental setups, and Q.Z. and A.S. performed optical experiments. A.S. carried out the spectroscopy measurements and optical microscopy. A.K.Y. and Q.Z. analyzed data and wrote the manuscript. S.H.Y. and H.B. made intellectual contributions and edited the article. H.B. thanks the Leverhulme Trust for research funding. NR 25 TC 7 Z9 7 U1 4 U2 20 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 SEP PY 2015 VL 9 IS 9 BP 9062 EP 9069 DI 10.1021/acsnano.5b03165 PG 8 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA CS2XR UT WOS:000361935800044 PM 26301907 ER PT J AU Kraft, S Tsao, H AF Kraft, S. Tsao, H. TI Melanoma-associated naevi: precursors or coincidence? SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Editorial Material C1 [Kraft, S.] Harvard Univ, Sch Med, Dermatopathol Serv, Boston, MA 02115 USA. [Tsao, H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. RP Kraft, S (reprint author), Harvard Univ, Sch Med, Dermatopathol Serv, Boston, MA 02115 USA. EM skraft@mgh.harvard.edu; htsao@mgh.harvard.edu NR 14 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD SEP PY 2015 VL 173 IS 3 BP 633 EP 634 DI 10.1111/bjd.14059 PG 2 WC Dermatology SC Dermatology GA CS6GQ UT WOS:000362176800002 PM 26404570 ER PT J AU Ona, K Oh, DH AF Ona, K. Oh, D. H. TI Voriconazole N-oxide and its ultraviolet B photoproduct sensitize keratinocytes to ultraviolet A SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; LUNG-TRANSPLANT RECIPIENTS; NUCLEOTIDE EXCISION-REPAIR; LONG-TERM VORICONAZOLE; CYTOCHROME-P450 ENZYMES; SKIN-CANCER; DNA; PHOTOSENSITIVITY; PHOTOTOXICITY; THERAPY AB Background The antifungal agent, voriconazole, is associated with phototoxicity and photocarcinogenicity. Prior work has indicated that voriconazole and its hepatic N-oxide metabolite do not sensitize keratinocytes to ultraviolet B (UVB). Clinical observations have suggested that ultraviolet A (UVA) may be involved. Objectives To determine the photochemistry and photobiology of voriconazole and its major hepatic metabolite, voriconazole N-oxide. Materials and methods Voriconazole and voriconazole N-oxide were spectrophotometrically monitored following various doses of UVB. Cultured human keratinocytes were treated with parental drugs or with their UVB photoproducts, and survival following UVA irradiation was measured by thiazolyl blue metabolism. Reactive oxygen species (ROS) and 8-oxoguanine were monitored by fluorescence microscopy. Results Voriconazole and voriconazole N-oxide have varying UVB absorption but do not acutely sensitize cultured human keratinocytes following UVB exposure. However, sustained UVB exposures produced notable dose- and solvent-dependent changes in the absorption spectra of voriconazole N-oxide, which in aqueous solution acquires a prominent UVA absorption band, suggesting formation of a discrete photoproduct. Neither the parental drugs nor their photoproducts sensitized cells to UVB although all but voriconazole N-oxide were moderately toxic to cells in the dark. Notably, both voriconazole N-oxide and its UVB photoproduct, but not voriconazole or its photoproduct, additionally sensitized cells to UVA by greater than three-fold relative to controls in association with UVA-induced ROS and 8-oxoguanine levels. Conclusions Voriconazole N-oxide and its UVB-photoproduct act as UVA-sensitizers that generate ROS and that produce oxidative DNA damage. These results suggest a mechanism for the phototoxicity and photocarcinogenicity observed with voriconazole treatment. C1 [Ona, K.; Oh, D. H.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Ona, K.; Oh, D. H.] San Francisco VA Med Ctr, Dermatol Res Unit, San Francisco, CA 94121 USA. RP Oh, DH (reprint author), San Francisco VA Med Ctr, Dermatol Res Unit, 4150 Clement St, San Francisco, CA 94121 USA. EM ohd@derm.ucsf.edu FU VA Merit Award; NIH Grant [AR064958] FX VA Merit Award and NIH Grant AR064958. NR 35 TC 3 Z9 3 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD SEP PY 2015 VL 173 IS 3 BP 751 EP 759 DI 10.1111/bjd.13862 PG 9 WC Dermatology SC Dermatology GA CS6GQ UT WOS:000362176800019 PM 25919127 ER PT J AU Yardley, DA Krop, IE LoRusso, PM Mayer, M Barnett, B Yoo, B Perez, EA AF Yardley, Denise A. Krop, Ian E. LoRusso, Patricia M. Mayer, Musa Barnett, Brian Yoo, Bongin Perez, Edith A. TI Trastuzumab Emtansine (T-DM1) in Patients With HER2-Positive Metastatic Breast Cancer Previously Treated With Chemotherapy and 2 or More HER2-Targeted Agents Results From the T-PAS Expanded Access Study SO CANCER JOURNAL LA English DT Article DE Ado-trastuzumab emtansine; breast cancer; expanded access trials; human epidermal growth factor receptor 2; metastases; T-DM1 ID PERTUZUMAB PLUS TRASTUZUMAB; PHASE-II; ADJUVANT CHEMOTHERAPY; MONOCLONAL-ANTIBODY; OPEN-LABEL; RECEPTOR; SAFETY; ANTHRACYCLINE; AMPLIFICATION; CAPECITABINE AB Purpose The antibody-drug conjugate trastuzumab emtansine (T-DM1) has improved outcomes in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC), as demonstrated in phase III studies. Few data approximating its use in routine clinical practice are available. Methods The T-DM1 Patient Access Study was an expanded-access, multicenter study of T-DM1 in US patients with pretreated HER2-positive locally advanced breast cancer or MBC. The primary endpoint was safety. The secondary endpoint was investigator-assessed objective response rate among patients with measurable disease at baseline. Data are presented for the first 215 enrolled patients. Results The median number of prior systemic MBC agents was 8 (range, 3-23). At baseline, median left ventricular ejection fraction was 60%, and 52.6% of patients had nonclinically significant cardiovascular disease. Median T-DM1 treatment duration was 5.0 months (range, 0-29 months; median follow-up, 5.9 months), with 18.6% having received more than 18 cycles. The most common any-grade adverse events were fatigue (50.7%) and nausea (38.1%). Adverse events of grade 3 or greater were reported in 46.5%, most commonly thrombocytopenia and platelet count decrease (10.2%). Bleeding of grade 3 or greater was reported in 4 patients (1.9%). Cardiac dysfunction (primarily asymptomatic left ventricular ejection fraction decreases) was reported in 14 patients (6.5%). Among those with measurable disease at baseline (n = 172), objective response rate was 25.6% (95% confidence interval, 19.2%-32.8%). Discussion The safety profile of T-DM1 in this real-world setting of heterogeneous, HER2-positive, pretreated, locally advanced breast cancer or MBC was comparable with that reported in phases II and III studies of similar patient populations. T-DM1 was efficacious with no new safety signals. C1 [Yardley, Denise A.] Tennessee Oncol PLLC, Sarah Cannon Res Inst, Breast Canc Res, Nashville, TN USA. [Yardley, Denise A.] Tennessee Oncol PLLC, Med Oncol, Nashville, TN USA. [Krop, Ian E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [LoRusso, Patricia M.] Yale Univ, Smilow Canc Ctr, New Haven, CT USA. [Mayer, Musa] AdvancedBC Org, New York, NY USA. [Barnett, Brian; Yoo, Bongin] Genentech Inc, San Francisco, CA 94080 USA. [Perez, Edith A.] Mayo Clin, Jacksonville, FL 32224 USA. RP Yardley, DA (reprint author), Tennessee Oncol, Sarah Cannon Res Inst, 250 25th Ave N,Suite 100, Nashville, TN 37203 USA. EM dyardley@tnonc.com FU Genentech, Inc. FX D.A.Y. has served as a consultant for Genentech, Inc. I.E.K. has received research funding from Genentech, Inc. P.M.L. has served on a speakers' bureau and as a consultant for Genentech, Inc. B.B. and B.Y. are salaried employees of Genentech, Inc, and own stock in F. Hoffmann-La Roche. M.M. and E.A.P. have nothing to disclose. The T-PAS expanded access study was funded by Genentech, Inc. NR 26 TC 1 Z9 1 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1528-9117 EI 1540-336X J9 CANCER J JI Cancer J. PD SEP-OCT PY 2015 VL 21 IS 5 BP 357 EP 364 DI 10.1097/PPO.0000000000000144 PG 8 WC Oncology SC Oncology GA CS6HD UT WOS:000362178300001 PM 26389758 ER PT J AU Piotrowska, Z Sequist, LV AF Piotrowska, Zofia Sequist, Lecia V. TI Epidermal Growth Factor Receptor-Mutant Lung Cancer New Drugs, New Resistance Mechanisms, and Future Treatment Options SO CANCER JOURNAL LA English DT Review DE Acquired resistance; circulating tumor DNA; EGFR; lung cancer; targeted therapies ID EGFR MUTATIONS; OPEN-LABEL; ACQUIRED-RESISTANCE; 1ST-LINE TREATMENT; KINASE INHIBITORS; PHASE-III; GEFITINIB; CHEMOTHERAPY; ERLOTINIB; AFATINIB AB Epidermal growth factor receptor (EGFR) mutations define a subset of non-small cell lung cancers that are sensitive to EGFR-targeted tyrosine kinase inhibitors (TKIs). Treatment with EGFR TKIs improves outcomes for patients whose tumors harbor these mutations, but their efficacy is limited by the development of acquired resistance. The secondary gatekeeper mutation, T790M, is the most common resistance mechanism observed in patients who progress on erlotinib and gefitinib, and a new class of drugs has recently been developed to target mutant EGFR and T790M. Here, we review the latest data with each generation of EGFR inhibitors and discuss emerging resistance mechanisms that have been observed in patients who have progressed on the latest class of EGFR TKIs. Looking ahead, combination treatment strategies in the frontline and resistant setting may be required to promote more durable responses and delay the development of resistance, and longitudinal analyses of plasma circulating tumor DNA may allow for earlier detection of emerging resistance mutations. C1 [Piotrowska, Zofia] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Piotrowska, Z (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,POB221, Boston, MA 02114 USA. EM zpiotrowska@partners.org NR 39 TC 10 Z9 12 U1 0 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1528-9117 EI 1540-336X J9 CANCER J JI Cancer J. PD SEP-OCT PY 2015 VL 21 IS 5 BP 371 EP 377 DI 10.1097/PPO.0000000000000147 PG 7 WC Oncology SC Oncology GA CS6HD UT WOS:000362178300004 PM 26389761 ER PT J AU Ercan, D Choi, HG Yun, CH Capelletti, M Xie, T Eck, MJ Gray, NS Janne, PA AF Ercan, Dalia Choi, Hwan Geun Yun, Cai-Hong Capelletti, Marzia Xie, Ting Eck, Michael J. Gray, Nathanael S. Jaenne, Pasi A. TI EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR Inhibitors SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; GROWTH-FACTOR RECEPTOR; RANDOMIZED PHASE-3 TRIAL; KINASE INHIBITORS; ACQUIRED-RESISTANCE; 1ST-LINE TREATMENT; OPEN-LABEL; ACTIVATING MUTATIONS; DRUG-RESISTANCE; KRAS MUTATIONS AB Purpose: Mutant selective irreversible pyrimidine-based EGFR kinase inhibitors, includingWZ4002, CO-1686, and AZD9291, are effective in preclinical models and in lung cancer patients harboring the EGFR T790M gefitinib/erlotinib resistance mutation. However, little is known about how cancers develop acquired resistance to this class of EGFR inhibitors. We sought to identify and study EGFR mutations that confer resistance to this class of agents. Experimental Design: We performed an N-ethyl-N-nitrosourea (ENU) mutagenesis screen in EGFR-mutant (sensitizing alone or with concurrent EGFR T790M) Ba/F3 cells and selected drug-resistant clones. We evaluated the sensitivity of EGFR inhibitors in models harboring drug-resistant EGFR mutations. Results: We identified 3 major drug resistance mutations. EGFR L718Q, L844V, and C797S cause resistance to both WZ4002 and CO-1686 while, in contrast, only EGFR C797S leads to AZD9291 resistance. Cells containing an EGFR-sensitizing mutation, Del 19 or L858R, in conjunction with L718Q, L844V, or C797S retain sensitivity to quinazoline-based EGFR inhibitors, gefitinib and afatinib. The C797S mutation, in the presence of Del 19 or L858R and T790M, causes resistance to all current EGFR inhibitors, but L858R/T790M/C797S remains partially sensitive to cetuximab which leads to disruption of EGFR dimerization. Conclusions: Our findings provide insights into resistance mechanisms to irreversible pyrimidine-based EGFR inhibitors and identify specific genomic contexts in which sensitivity is retained to existing clinical EGFR inhibitors. These findings will guide the development of new strategies to inhibit EGFR. (C)2015 AACR. C1 [Ercan, Dalia; Capelletti, Marzia; Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02215 USA. [Choi, Hwan Geun; Yun, Cai-Hong; Xie, Ting; Eck, Michael J.; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Choi, Hwan Geun; Yun, Cai-Hong; Xie, Ting; Eck, Michael J.; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Yun, Cai-Hong] Peking Univ, Hlth Sci Ctr, Inst Syst Biomed, Dept Biophys,Sch Basic Med Sci, Beijing 100871, Peoples R China. [Jaenne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Jaenne, Pasi A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 450 Brookline Ave,HIM 223, Boston, MA 02215 USA. EM Nathanael_Gray@dfci.harvard.edu; pasi_janne@dfci.harvard.edu FU NIH [RO1CA114465, R01CA135257, PO1CA154303]; Cammarata Family Foundation Research Fund; Nirenberg Fellowship at Dana Farber Cancer Institute FX This study is supported by grants from the NIH RO1CA114465 (to P.A. Janne), R01CA135257 (to P.A. Janne), PO1CA154303 (to P.A. Janne, M.J. Eck, and N.S. Gray), the Cammarata Family Foundation Research Fund (to M. Capelletti and P.A. Janne), and the Nirenberg Fellowship at Dana Farber Cancer Institute (to M. Capelletti and P.A. Janne). NR 38 TC 47 Z9 49 U1 3 U2 18 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 SEP 1 PY 2015 VL 21 IS 17 BP 3913 EP 3923 DI 10.1158/1078-0432.CCR-14-2789 PG 11 WC Oncology SC Oncology GA CS2OF UT WOS:000361910000015 PM 25948633 ER PT J AU Niederst, MJ Hu, HC Mulvey, HE Lockerman, EL Garcia, AR Piotrowska, Z Sequist, LV Engelman, JA AF Niederst, Matthew J. Hu, Haichuan Mulvey, Hillary E. Lockerman, Elizabeth L. Garcia, Angel R. Piotrowska, Zofia Sequist, Lecia V. Engelman, Jeffrey A. TI The Allelic Context of the C797S Mutation Acquired upon Treatment with Third-Generation EGFR Inhibitors Impacts Sensitivity to Subsequent Treatment Strategies SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; TYROSINE KINASE INHIBITORS; DRUG-COMBINATIONS; RESISTANCE; GEFITINIB; CHEMOTHERAPY; T790M; AMPLIFICATION; ERLOTINIB; AFATINIB AB Purpose: A secondary EGFR mutation, T790M, is the most common resistance mechanism in EGFR-mutant adenocarcinomas that have progressed on erlotinib. Third-generation EGFR inhibitors capable of inhibiting mutant EGFR with T790M produce responses in nearly two thirds of patients. However, acquired resistance mechanisms in patients treated with these drugs are yet to be described. Experimental Design: To study acquired resistance to third-generation EGFR inhibitors, T790M-positive cells derived from an erlotinib-resistant cancer were made resistant to a third-generation TKI and then characterized using cell and molecular analyses. Results: Cells resistant to a third-generation TKI acquired an additional EGFR mutation, C797S, which prevented suppression of EGFR. Our results demonstrate that the allelic context in which C797S was acquired may predict responsiveness to alternative treatments. If the C797S and T790M mutations are in trans, cells will be resistant to third-generation EGFR TKIs, but will be sensitive to a combination of first-and third-generation TKIs. If the mutations are in cis, no EGFR TKIs alone or in combination can suppress activity. If C797S develops in cells wild-type for T790 (when third-generation TKIs are administered in the first-line setting), the cells are resistant to third-generation TKIs, but retain sensitivity to first-generation TKIs. Conclusions: Mutation of C797S in EGFR is a novel mechanism of acquired resistance to third-generation TKIs. The context in which the C797S develops with respect to the other EGFR alleles affects the efficacy of subsequent treatments. (C)2015 AACR. C1 [Niederst, Matthew J.; Hu, Haichuan; Mulvey, Hillary E.; Lockerman, Elizabeth L.; Garcia, Angel R.; Piotrowska, Zofia; Sequist, Lecia V.; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Niederst, Matthew J.; Hu, Haichuan; Mulvey, Hillary E.; Lockerman, Elizabeth L.; Garcia, Angel R.; Piotrowska, Zofia; Sequist, Lecia V.; Engelman, Jeffrey A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Engelman, JA (reprint author), 149 13th St 7th Floor, Charlestown, MA 02129 USA. EM jengelman@mgh.harvard.edu FU NIH [R01CA137008]; Department of Defense; LunGevity; Uniting Against Lung Cancer; Lung Cancer Research Foundation; Targeting a Cure for Lung Cancer; Be a Piece of the Solution FX This study was funded by support from the NIH R01CA137008 (J.A. Engelman), the Department of Defense (L.V. Sequist and J.A. Engelman), LunGevity (L.V. Sequist and J.A. Engelman), Uniting Against Lung Cancer (Z. Piotrowska and M.J. Niederst), Lung Cancer Research Foundation (M.J. Niederst), Targeting a Cure for Lung Cancer, and Be a Piece of the Solution. NR 42 TC 52 Z9 53 U1 0 U2 11 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 SEP 1 PY 2015 VL 21 IS 17 BP 3924 EP 3933 DI 10.1158/1078-0432.CCR-15-0560 PG 10 WC Oncology SC Oncology GA CS2OF UT WOS:000361910000016 PM 25964297 ER PT J AU Cagnetta, A Caffa, I Acharya, C Soncini, D Acharya, P Adamia, S Pierri, I Bergamaschi, M Garuti, A Fraternali, G Mastracci, L Provenzani, A Zucal, C Damonte, G Salis, A Montecucco, F Patrone, F Ballestrero, A Bruzzone, S Gobbi, M Nencioni, A Cea, M AF Cagnetta, Antonia Caffa, Irene Acharya, Chirag Soncini, Debora Acharya, Prakrati Adamia, Sophia Pierri, Ivana Bergamaschi, Micaela Garuti, Anna Fraternali, Giulio Mastracci, Luca Provenzani, Alessandro Zucal, Chiara Damonte, Gianluca Salis, Annalisa Montecucco, Fabrizio Patrone, Franco Ballestrero, Alberto Bruzzone, Santina Gobbi, Marco Nencioni, Alessio Cea, Michele TI APO866 Increases Antitumor Activity of Cyclosporin-A by Inducing Mitochondrial and Endoplasmic Reticulum Stress in Leukemia Cells SO CLINICAL CANCER RESEARCH LA English DT Article ID ACUTE MYELOID-LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; UBIQUITIN-PROTEASOME SYSTEM; NAD BIOSYNTHESIS INHIBITOR; P-GLYCOPROTEIN INHIBITION; MULTIDRUG-RESISTANCE; NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE; HEMATOLOGIC MALIGNANCIES; EXPRESSION SIGNATURE; DRUG-RESISTANCE AB Purpose: The nicotinamide phosphoribosyltransferase (NAMPT) inhibitor, APO866, has been previously shown to have antileukemic activity in preclinical models, but its cytotoxicity in primary leukemia cells is frequently limited. The success of current antileukemic treatments is reduced by the occurrence of multidrug resistance, which, in turn, is mediated by membrane transport proteins, such as P-glycoprotein-1 (Pgp). Here, we evaluated the antileukemic effects of APO866 in combination with Pgp inhibitors and studied the mechanisms underlying the interaction between these two types of agents. Experimental Design: The effects of APO866 with or without Pgp inhibitors were tested on the viability of leukemia cell lines, primary leukemia cells (AML, n = 6; B-CLL, n = 19), and healthy leukocytes. Intracellular nicotinamide adenine dinucleotide (NAD(+)) and ATP levels, mitochondrial transmembrane potential (Delta psi(m)), markers of apoptosis and of endoplasmic reticulum (ER) stress were evaluated. Results: The combination of APO866 with Pgp inhibitors resulted in a synergistic cytotoxic effect in leukemia cells, while sparing normal CD34(+) progenitor cells and peripheral blood mononuclear cells. Combining Pgp inhibitors with APO866 led to increased intracellular APO866 levels, compounded NAD(+) and ATP shortage, and induced Delta psi(m) dissipation. Notably, APO866, Pgp inhibitors and, to a much higher extent, their combination induced ER stress and ER stress inhibition strongly reduced the activity of these treatments. Conclusions: APO866 and Pgp inhibitors show a strong synergistic cooperation in leukemia cells, including acute myelogenous leukemia (AML) and B-cell chronic lymphocytic leukemia (B-CLL) samples. Further evaluations of the combination of these agents in clinical setting should be considered. (C) 2015 AACR. C1 [Cagnetta, Antonia; Caffa, Irene; Soncini, Debora; Pierri, Ivana; Bergamaschi, Micaela; Garuti, Anna; Patrone, Franco; Ballestrero, Alberto; Gobbi, Marco; Nencioni, Alessio; Cea, Michele] IRCCS AOU S Martino IST, Dept Hematology & Oncol, Genoa, Italy. [Cagnetta, Antonia; Acharya, Chirag; Adamia, Sophia; Cea, Michele] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Acharya, Prakrati] Harvard Univ, Sch Med, Mt Auburn Hosp, Cambridge, MA 02138 USA. [Fraternali, Giulio] IRCCS AUO S Martino IST, Labs Dept, Pathol Unit, Genoa, Italy. [Mastracci, Luca] IRCCS AUO S Martino IST, Dept Surg & Diagnost Sci DISC, Pathol Unit, Genoa, Italy. [Provenzani, Alessandro] Univ Trento, Ctr Integrat Biol, Trento, Italy. [Zucal, Chiara; Damonte, Gianluca; Salis, Annalisa; Bruzzone, Santina] Univ Genoa, Dept Expt Med, Biochem Sect, I-16126 Genoa, Italy. [Zucal, Chiara; Damonte, Gianluca; Salis, Annalisa; Bruzzone, Santina] Univ Genoa, CEBR, I-16126 Genoa, Italy. [Montecucco, Fabrizio] Univ Geneva, Div Cardiol, Dept Internal Med, Fdn Med Res, Geneva, Switzerland. [Montecucco, Fabrizio] Univ Geneva, Dept Med Specialties, Geneva, Switzerland. RP Cea, M (reprint author), Univ Genoa, I-16132 Genoa, Italy. EM alessio.nencioni@unige.it; michele.cea@unige.it RI Caffa, Irene/J-9835-2016; Provenzani, Alessandro/I-9211-2012; Montecucco, Fabrizio/K-8543-2016 OI Caffa, Irene/0000-0003-1111-9915; Provenzani, Alessandro/0000-0003-1652-3415; Montecucco, Fabrizio/0000-0003-0823-8729 FU Associazione Italiana per la Ricerca sul Cancro [6108]; Italian Ministry of Health grant [GR-2008-1135635]; Compagnia di San Paolo [R.O.L. 689]; Fondazione Umberto Veronesi; Associazione Cristina Bassi; American Italian Cancer Foundation; European Community [HEALTH-F2-2013-256986] FX This work was supported in part by the Associazione Italiana per la Ricerca sul Cancro (#6108; to A. Nencioni); by the Italian Ministry of Health grant GR-2008-1135635 (to A. Nencioni); by the Compagnia di San Paolo (R.O.L. 689; to A. Nencioni); by the Fondazione Umberto Veronesi (to A. Nencioni); by the Associazione Cristina Bassi (to A. Cagnetta) and by the American Italian Cancer Foundation (to M. Cea). In addition, the research leading to these results has received funding from the European Community's Seventh Framework Program [FP7-2007-2013] under grant agreement no HEALTH-F2-2013-256986 (Panacreas). NR 58 TC 8 Z9 8 U1 1 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 SEP 1 PY 2015 VL 21 IS 17 BP 3934 EP 3945 DI 10.1158/1078-0432.CCR-14-3023 PG 12 WC Oncology SC Oncology GA CS2OF UT WOS:000361910000017 PM 25964294 ER PT J AU Ota, K Azuma, K Kawahara, A Hattori, S Iwama, E Tanizaki, J Harada, T Matsumoto, K Takayama, K Takamori, S Kage, M Hoshino, T Nakanishi, Y Okamoto, I AF Ota, Keiichi Azuma, Koichi Kawahara, Akihiko Hattori, Satoshi Iwama, Eiji Tanizaki, Junko Harada, Taishi Matsumoto, Koichiro Takayama, Koichi Takamori, Shinzo Kage, Masayoshi Hoshino, Tomoaki Nakanishi, Yoichi Okamoto, Isamu TI Induction of PD-L1 Expression by the EML4-ALK Oncoprotein and Downstream Signaling Pathways in Non-Small Cell Lung Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID ALK KINASE INHIBITOR; EGFR MUTATIONS; FUSION GENE; B7-H1 PD-L1; GEFITINIB; CHEMOTHERAPY; ACTIVATION; RESISTANCE; CARCINOMA; IMMUNORESISTANCE AB Purpose: Therapies targeted to the immune checkpoint mediated by PD-1 and PD-L1 show antitumor activity in a subset of patients with non-small cell lung cancer (NSCLC). We have now examined PD-L1 expression and its regulation in NSCLC positive for the EML4-ALK fusion gene. Experimental Design: The expression of PD-L1 at the protein and mRNA levels in NSCLC cell lines was examined by flow cytometry and by reverse transcription and real-time PCR analysis, respectively. The expression of PD-L1 in 134 surgically resected NSCLC specimens was evaluated by immunohistochemical analysis. Results: The PD-L1 expression level was higher in NSCLC cell lines positive for EML4-ALK than in those negative for the fusion gene. Forced expression of EML4-ALK in Ba/F3 cells markedly increased PD-L1 expression, whereas endogenous PD-L1 expression in EML4-ALK-positive NSCLC cells was attenuated by treatment with the specific ALK inhibitor alectinib or by RNAi with ALK siRNAs. Furthermore, expression of PD-L1 was downregulated by inhibitors of the MEK-ERK and PI3K-AKT signaling pathways in NSCLC cells positive for either EML4-ALK or activating mutations of the EGFR. Finally, the expression level of PD-L1 was positively associated with the presence of EML4-ALK in NSCLC specimens. Conclusions: Our findings that both EML4-ALK and mutant EGFR upregulate PD-L1 by activating PI3K-AKT and MEK-ERK signaling pathways in NSCLC reveal a direct link between oncogenic drivers and PD-L1 expression. (C)2015 AACR. C1 [Ota, Keiichi; Iwama, Eiji; Harada, Taishi; Matsumoto, Koichiro; Takayama, Koichi; Nakanishi, Yoichi; Okamoto, Isamu] Kyushu Univ, Res Inst Dis Chest, Grad Sch Med Sci, Fukuoka 812, Japan. [Azuma, Koichi; Hoshino, Tomoaki] Kurume Univ, Sch Med, Div Respirol Neurol & Rheumatol, Dept Internal Med, Fukuoka, Japan. [Kawahara, Akihiko; Kage, Masayoshi] Kurume Univ Hosp, Dept Diagnost Pathol, Fukuoka, Japan. [Hattori, Satoshi] Kurume Univ, Biostat Ctr, Fukuoka, Japan. [Iwama, Eiji] Kyushu Univ, Fac Med Sci, Dept Comprehens Clin Oncol, Fukuoka 812, Japan. [Tanizaki, Junko] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Takamori, Shinzo] Kurume Univ, Sch Med, Dept Surg, Fukuoka, Japan. [Nakanishi, Yoichi; Okamoto, Isamu] Kyushu Univ Hosp, Ctr Clin & Translat Res, Fukuoka 812, Japan. RP Okamoto, I (reprint author), Kyushu Univ Hosp, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan. EM okamotoi@kokyu.med.kyushu-u.ac.jp RI U-ID, Kyushu/C-5291-2016 NR 39 TC 56 Z9 58 U1 9 U2 23 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 SEP 1 PY 2015 VL 21 IS 17 BP 4014 EP 4021 DI 10.1158/1078-0432.CCR-15-0016 PG 8 WC Oncology SC Oncology GA CS2OF UT WOS:000361910000025 PM 26019170 ER PT J AU Simon, DK Wu, C Tilley, BC Wills, AM Aminoff, MJ Bainbridge, J Hauser, RA Schneider, JS Sharma, S Singer, C Tanner, CM Truong, D Wong, PS AF Simon, David K. Wu, Cai Tilley, Barbara C. Wills, Anne-Marie Aminoff, Michael J. Bainbridge, Jacquelyn Hauser, Robert A. Schneider, Jay S. Sharma, Saloni Singer, Carlos Tanner, Caroline M. Daniel Truong Wong, Pei Shieen TI Caffeine and Progression of Parkinson Disease: A Deleterious Interaction With Creatine SO CLINICAL NEUROPHARMACOLOGY LA English DT Review DE Parkinson disease; caffeine; coffee; creatine; supplement; movement disorders; clinical study; neuroprotection; progression; interaction; association; adenosine A2a receptor antagonist: LS1; NET-PD ID CLINICAL-TRIAL; ADENOSINE; RISK; CONSUMPTION; COFFEE AB Objective Increased caffeine intake is associated with a lower risk of Parkinson disease (PD) and is neuroprotective in mouse models of PD. However, in a previous study, an exploratory analysis suggested that, in patients taking creatine, caffeine intake was associated with a faster rate of progression. In the current study, we investigated the association of caffeine with the rate of progression of PD and the interaction of this association with creatine intake. Methods Data were analyzed from a large phase 3 placebo-controlled clinical study of creatine as a potentially disease-modifying agent in PD. Subjects were recruited for this study from 45 movement disorders centers across the United States and Canada. A total of 1741 subjects with PD participated in the primary clinical study, and caffeine intake data were available for 1549 of these subjects. The association of caffeine intake with rate of progression of PD as measured by the change in the total Unified Parkinson Disease Rating Scale score and the interaction of this association with creatine intake were assessed. Results Caffeine intake was not associated with the rate of progression of PD in the main analysis, but higher caffeine intake was associated with significantly faster progression among subjects taking creatine. Conclusions This is the largest and longest study conducted to date that addresses the association of caffeine with the rate of progression of PD. These data indicate a potentially deleterious interaction between caffeine and creatine with respect to the rate of progression of PD. C1 [Simon, David K.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Simon, David K.; Wills, Anne-Marie] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Wu, Cai; Tilley, Barbara C.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Dept Biostat, Houston, TX 77030 USA. [Wills, Anne-Marie] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Aminoff, Michael J.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Bainbridge, Jacquelyn; Wong, Pei Shieen] Univ Colorado, Dept Clin Pharm & Neurol, Skaggs Sch Pharm & Pharmaceut Sci, Aurora, CO USA. [Hauser, Robert A.] Univ S Florida, Dept Neurol, Tampa, FL 33620 USA. [Schneider, Jay S.] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Parkinsons Dis Res Unit, Philadelphia, PA 19107 USA. [Sharma, Saloni] Univ Rochester, Med Ctr, Clin Trials Coordinat Ctr, Rochester, NY 14642 USA. [Singer, Carlos] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. [Tanner, Caroline M.] San Francisco VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, San Francisco, CA USA. [Daniel Truong] Parkinsons & Movement Disorder Inst, Fountain Valley, CA USA. [Wong, Pei Shieen] Singapore Gen Hosp, Singapore, Singapore. RP Simon, DK (reprint author), Beth Israel Deaconess Med Ctr, Dept Neurol, 330 Brookline Ave, Boston, MA 02215 USA. EM dsimon1@bidmc.harvard.edu FU National Institute of Neurological Disorders and Stroke; Merck FX The study was funded by the National Institute of Neurological Disorders and Stroke. Dr Wills participated as a site investigator in the Preladenant clinical trials funded by Merck. Other authors have no relevant conflicts of interest. NR 21 TC 2 Z9 2 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0362-5664 EI 1537-162X J9 CLIN NEUROPHARMACOL JI Clin. Neuropharmacol. PD SEP-OCT PY 2015 VL 38 IS 5 BP 163 EP 169 DI 10.1097/WNF.0000000000000102 PG 7 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA CS5HF UT WOS:000362107900001 PM 26366971 ER PT J AU Vinegoni, C Dubach, JM Thurber, GM Miller, MA Mazitschek, R Weissleder, R AF Vinegoni, Claudio Dubach, J. Matthew Thurber, Greg M. Miller, Miles A. Mazitschek, Ralph Weissleder, Ralph TI Advances in measuring single-cell pharmacology in vivo SO DRUG DISCOVERY TODAY LA English DT Review ID TARGET ENGAGEMENT; DRUG DISCOVERY; HETEROGENEITY; RESOLUTION; MODELS AB Measuring key pharmacokinetic and pharmacodynamic parameters in vivo at the single cell level is likely to enhance drug discovery and development. In this review, we summarize recent advances in this field and highlight current and future capabilities. C1 [Vinegoni, Claudio; Dubach, J. Matthew; Miller, Miles A.; Mazitschek, Ralph; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Vinegoni, Claudio; Dubach, J. Matthew; Miller, Miles A.; Mazitschek, Ralph; Weissleder, Ralph] Harvard Univ, Sch Med, Richard B Simches Res Ctr, Boston, MA 02114 USA. [Thurber, Greg M.] Univ Michigan, Dept Biomed Engn, Dept Chem Engn, Ann Arbor, MI 48109 USA. RP Vinegoni, C (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM cvinegoni@mgh.harvard.edu OI Thurber, Greg/0000-0001-7570-2080 FU National Heart, Lung and Blood Institute, National Institutes of Health, Department of Health and Human Services [HHSN268201000044C]; National Cancer Institute [T32CA079443, P50 CA086355]; Institute of Biomedical Engineering [R01EB006432] FX The authors acknowledge funding from the National Heart, Lung and Blood Institute, National Institutes of Health, Department of Health and Human Services (contract no. HHSN268201000044C), the National Cancer Institute (T32CA079443, P50 CA086355) and from the Institute of Biomedical Engineering (R01EB006432). NR 31 TC 1 Z9 1 U1 5 U2 20 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 EI 1878-5832 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD SEP PY 2015 VL 20 IS 9 BP 1087 EP 1092 DI 10.1016/j.drudis.2015.05.011 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CS2UR UT WOS:000361928000007 PM 26024776 ER PT J AU Cox, KH AF Cox, Kimberly H. TI A Kiss and a PRomise SO ENDOCRINOLOGY LA English DT Editorial Material ID LUTEINIZING-HORMONE SURGE; ROSTRAL PERIVENTRICULAR AREA; MESSENGER-RIBONUCLEIC-ACID; KISSPEPTIN NEURONS; PROGESTERONE-RECEPTOR; FEMALE MOUSE; GONADOTROPIN-SECRETION; POSITIVE FEEDBACK; ESTROGEN; GPR54 C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Cox, KH (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, 55 Fruit St,Bartlett Hall Extens,Fifth Floor, Boston, MA 02114 USA. EM khcox@mgh.harvard.edu RI Cox, Kimberly/P-1931-2016 OI Cox, Kimberly/0000-0002-7097-9563 FU NICHD NIH HHS [U54 HD028138, P50 HD028138, T32 HD007396] NR 47 TC 0 Z9 0 U1 0 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2015 VL 156 IS 9 BP 3063 EP 3065 DI 10.1210/EN.2015-1602 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CS6ZV UT WOS:000362234100002 PM 26295491 ER PT J AU Banks, WA AF Banks, William A. TI A Vagina Monologue: Mom's Stress, Bugs, and Baby's Brain SO ENDOCRINOLOGY LA English DT Editorial Material C1 [Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Banks, William A.] Univ Washington, Sch Med, Div Gerontol & Geriatr Med, Dept Med, Seattle, WA 98108 USA. RP Banks, WA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. FU NIA NIH HHS [R01 AG046619] NR 14 TC 3 Z9 3 U1 2 U2 6 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2015 VL 156 IS 9 BP 3066 EP 3068 DI 10.1210/EN.2015-1590 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CS6ZV UT WOS:000362234100003 PM 26295492 ER PT J AU Carmody, JS Ahmad, NN Machineni, S Lajoie, S Kaplan, LM AF Carmody, Jill S. Ahmad, Nadia N. Machineni, Sriram Lajoie, Scott Kaplan, Lee M. TI Weight Loss After RYGB Is Independent of and Complementary to Serotonin 2C Receptor Signaling in Male Mice SO ENDOCRINOLOGY LA English DT Article ID Y GASTRIC BYPASS; NEURONS REGULATE ENERGY; MELANOCORTIN-4 RECEPTOR; BARIATRIC SURGERY; GLUCOSE-HOMEOSTASIS; MEDICAL THERAPY; IN-VIVO; FENFLURAMINE; OBESITY; RATS AB Roux-en-Y gastric bypass (RYGB) typically leads to substantial, long-term weight loss (WL) and diabetes remission, although there is a wide variation in response to RYGB among individual patients. Defining the pathways through which RYGB works should aid in the development of less invasive anti-obesity treatments, whereas identifying weight-regulatory pathways unengaged by RYGB could facilitate the development of therapies that complement the beneficial effects of surgery. Activation of serotonin 2C receptors (5-HT2CR) by serotonergic drugs causes WL in humans and animal models. 5-HT2CR are located on neurons that activate the melanocortin-4 receptors, which are essential for WL after RYGB. We therefore sought to determine whether 5-HT2CR signaling is also essential for metabolic effects of RYGB or whether it is a potentially complementary pathway, the activation of which could extend the benefits of RYGB. Diet-induced obese male mice deficient for the 5-HT2CR and their wild-type littermates underwent RYGB or sham operation. Both groups lost similar amounts of weight after RYGB, demonstrating that the improved metabolic phenotype after RYGB is 5-HT2CR independent. Consistent with this hypothesis, wild-type RYGB-treated mice lost additional weight after the administration of the serotonergic drugs fenfluramine and meta-chlorophenylpiperazine but not the nonserotonergic agent topiramate. The fact that RYGB does not depend on 5-HT2CR signaling suggests that there are important WL mechanisms not fully engaged by surgery that could potentially be harnessed for medical treatment. These results suggest a rational basis for designing medical-surgical combination therapies to optimize clinical outcomes by exploiting complementary physiological mechanisms of action. C1 [Carmody, Jill S.; Ahmad, Nadia N.; Machineni, Sriram; Lajoie, Scott; Kaplan, Lee M.] Massachusetts Gen Hosp, Obes Metab & Nutr Inst, Boston, MA 02114 USA. [Carmody, Jill S.; Ahmad, Nadia N.; Machineni, Sriram; Lajoie, Scott; Kaplan, Lee M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Carmody, Jill S.; Ahmad, Nadia N.; Machineni, Sriram; Kaplan, Lee M.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Kaplan, LM (reprint author), Massachusetts Gen Hosp, 149 13th St,Room 8219, Boston, MA 02129 USA. EM lmkaplan@mgh.harvard.edu FU National Institutes of Health [DK088661]; Ethicon, Inc. FX This work was supported by National Institutes of Health Grant DK088661 (to L.M.K.) and a research grant from Ethicon, Inc. NR 37 TC 3 Z9 3 U1 0 U2 4 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2015 VL 156 IS 9 BP 3183 EP 3191 DI 10.1210/en.2015-1226 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CS6ZV UT WOS:000362234100015 PM 26066076 ER PT J AU Haner, RL Krishnan, S AF Haner, Ronald L. Krishnan, Shoba TI Spiral Inductors With Floating Low-Loss RF Shields for LC Resonator Applications SO IEEE TRANSACTIONS ON COMPONENTS PACKAGING AND MANUFACTURING TECHNOLOGY LA English DT Article DE Floating shield; LC resonator; projected shield; Q measurement; RLC circuits; shielding ID QUALITY FACTOR; FREQUENCY; MICROWAVE; COILS; ICS AB A method for designing LC tank circuits to improve energy efficiency and reduce layout area is described. The approach uses a projected shield that is floating, overlaps the trace of the overlying inductor, and adds capacitance to the tank's inductor. Capacitance is distributed along the spiral traces, and the layout area is thus decreased. In this paper, we investigate the properties of spiral inductors with and without projected shielding, and compare the method with similar circuits including those with floating shields shaped as patterned ground shields. In addition, a measurement methodology for LC tank resonators is developed and presented. Test structures are implemented as microstrip spiral inductors and evaluated as LC tank circuits that resonate between 100 and 500 MHz. The Q values of shielded structures are up to 7% greater than those without shields, and area savings for LC resonators-compared with side-by-side layouts of L and C-are up to 35%. C1 [Haner, Ronald L.; Krishnan, Shoba] Santa Clara Univ, Dept Elect Engn, Santa Clara, CA 95053 USA. RP Haner, RL (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM ronhaner@gmail.com; skrishnan@scu.edu NR 36 TC 1 Z9 1 U1 4 U2 8 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 2156-3950 EI 2156-3985 J9 IEEE T COMP PACK MAN JI IEEE Trans. Compon. Pack. Manuf. Technol. PD SEP PY 2015 VL 5 IS 9 BP 1300 EP 1312 DI 10.1109/TCPMT.2015.2457237 PG 13 WC Engineering, Manufacturing; Engineering, Electrical & Electronic; Materials Science, Multidisciplinary SC Engineering; Materials Science GA CS2PK UT WOS:000361913200012 ER PT J AU Liu, YF Alexander, BM Chen, YH Horvath, MC Aizer, AA Claus, EB Dunn, IF Golby, AJ Johnson, MD Friesen, S Mannarino, EG Wagar, M Hacker, FL Arvold, ND AF Liu, Yufei Alexander, Brian M. Chen, Yu-Hui Horvath, Margaret C. Aizer, Ayal A. Claus, Elizabeth B. Dunn, Ian F. Golby, Alexandra J. Johnson, Mark D. Friesen, Scott Mannarino, Edward G. Wagar, Matthew Hacker, Fred L. Arvold, Nils D. TI Salvage whole brain radiotherapy or stereotactic radiosurgery after initial stereotactic radiosurgery for 1-4 brain metastases SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Brain metastases; Stereotactic radiosurgery; Whole brain radiotherapy; Salvage; Cause of death ID PROPHYLACTIC CRANIAL IRRADIATION; CELL LUNG-CANCER; RADIATION-THERAPY; SURGICAL RESECTION; SECONDARY ANALYSIS; RANDOMIZED-TRIAL; TUMORS; MANAGEMENT; SURVIVAL; OUTCOMES AB Patients with limited brain metastases are often candidates for stereotactic radiosurgery (SRS) or whole brain radiotherapy (WBRT). Among patients who receive SRS, the likelihood and timing of salvage WBRT or SRS remains unclear. We examined rates of salvage WBRT or SRS among 180 patients with 1-4 newly diagnosed brain metastases who received index SRS from 2008-2013. Competing risks multivariable analysis was used to examine factors associated with time to WBRT. Patients had non-small cell lung (53 %), melanoma (23 %), breast (10 %), renal (6 %), or other (8 %) cancers. Median age was 62 years. Patients received index SRS to 1 (60 %), 2 (21 %), 3 (13 %), or 4 (7 %) brain metastases. Median survival after SRS was 9.7 months (range, 0.3-67.6 months). No further brain-directed radiotherapy was delivered after index SRS in 55 % of patients. Twenty-seven percent of patients ever received salvage WBRT, and 30 % ever received salvage SRS; 12 % of patients received both salvage WBRT and salvage SRS. Median time to salvage WBRT or salvage SRS were 5.6 and 6.1 months, respectively. Age a parts per thousand currency sign60 years (adjusted hazard ratio [AHR] = 2.80; 95 % CI 1.05-7.51; P = 0.04) and controlled/absent extracranial disease (AHR = 6.76; 95 % CI 1.60-28.7; P = 0.01) were associated with shorter time to salvage WBRT. Isolated brain progression caused death in only 11 % of decedents. In summary, most patients with 1-4 brain metastases receiving SRS never require salvage WBRT or SRS, and the remainder do not require salvage treatment for a median of 6 months. C1 [Liu, Yufei; Alexander, Brian M.; Horvath, Margaret C.; Aizer, Ayal A.; Friesen, Scott; Mannarino, Edward G.; Wagar, Matthew; Hacker, Fred L.; Arvold, Nils D.] Harvard Univ, Dept Radiat Oncol, Dana Farber Brigham & Womens Canc Ctr, Sch Med, Boston, MA 02115 USA. [Chen, Yu-Hui] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Claus, Elizabeth B.; Dunn, Ian F.; Golby, Alexandra J.; Johnson, Mark D.] Harvard Univ, Dept Neurosurg, Dana Farber Brigham & Womens Canc Ctr, Sch Med, Boston, MA 02115 USA. [Claus, Elizabeth B.] Yale Univ, Sch Publ Hlth, New Haven, CT USA. RP Arvold, ND (reprint author), Harvard Univ, Dept Radiat Oncol, Dana Farber Brigham & Womens Canc Ctr, Sch Med, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM narvold@partners.org NR 31 TC 1 Z9 1 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD SEP PY 2015 VL 124 IS 3 BP 429 EP 437 DI 10.1007/s11060-015-1855-5 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CS2LJ UT WOS:000361902000011 PM 26108659 ER PT J AU Abou Al-Shaar, H Almefty, KK Abolfotoh, M Arvold, ND Devlin, PM Reardon, DA Loeffler, JS Al-Mefty, O AF Abou Al-Shaar, Hussam Almefty, Kaith K. Abolfotoh, Mohammad Arvold, Nils D. Devlin, Phillip M. Reardon, David A. Loeffler, Jay S. Al-Mefty, Ossama TI Brachytherapy in the treatment of recurrent aggressive falcine meningiomas SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Brachytherapy; I-125; Falcine; Meningioma; Atypical meningioma; Falcine meningioma ID HIGH-ACTIVITY I-125; BRAIN-TUMORS; SKULL BASE; PERMANENT BRACHYTHERAPY; GLIOBLASTOMA-MULTIFORME; CLINICAL ARTICLE; MANAGEMENT; RADIATION; RADIOSURGERY; RADIOTHERAPY AB Recurrent aggressive falcine meningiomas are uncommon tumors that recur despite receiving extensive surgery and radiation therapy (RT). We have utilized brachytherapy as a salvage treatment in two such patients with a unique implantation technique. Both patients had recurrence of WHO Grade II falcine meningiomas despite multiple prior surgical and RT treatments. Radioactive I-125 seeds were made into strands and sutured into a mesh implant, with 1 cm spacing, in a size appropriate to cover the cavity and region of susceptible falcine dura. Following resection the vicryl mesh was implanted and fixed to the margins of the falx. Implantation in this interhemispheric space provides good dose conformality with targeting of at-risk tissue and minimal radiation exposure to normal neural tissues. The patients are recurrence free 31 and 10 months after brachytherapy treatment. Brachytherapy was an effective salvage treatment for the recurrent aggressive falcine meningiomas in our two patients. C1 [Abou Al-Shaar, Hussam] Alfaisal Univ, Coll Med, Riyadh, Saudi Arabia. [Almefty, Kaith K.; Abolfotoh, Mohammad; Al-Mefty, Ossama] Harvard Univ, Sch Med, Dept Neurosurg, Brigham & Womens Hosp, Boston, MA 02115 USA. [Almefty, Kaith K.; Abolfotoh, Mohammad; Al-Mefty, Ossama] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. [Almefty, Kaith K.] St Josephs Hosp, Div Neurol Surg, Barrow Neurol Inst, Phoenix, AZ USA. [Arvold, Nils D.; Devlin, Phillip M.] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. [Reardon, David A.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. [Loeffler, Jay S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Loeffler, Jay S.] Harvard Univ, Sch Med, Boston, MA USA. RP Al-Mefty, O (reprint author), Harvard Univ, Sch Med, Dept Neurosurg, Brigham & Womens Hosp, 15 Francis St, Boston, MA 02115 USA. EM oalmefty@partners.org NR 40 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD SEP PY 2015 VL 124 IS 3 BP 515 EP 522 DI 10.1007/s11060-015-1873-3 PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CS2LJ UT WOS:000361902000021 PM 26253325 ER PT J AU Kitago, T Goldsmith, J Harran, M Kane, L Berard, J Huang, S Ryan, SL Mazzoni, P Krakauer, JW Huang, VS AF Kitago, Tomoko Goldsmith, Jeff Harran, Michelle Kane, Leslie Berard, Jessica Huang, Sylvia Ryan, Sophia L. Mazzoni, Pietro Krakauer, John W. Huang, Vincent S. TI Robotic therapy for chronic stroke: general recovery of impairment or improved task-specific skill? SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE stroke; neurorehabilitation; robotic therapy; kinematics; motor control ID UPPER-EXTREMITY FUNCTION; RESEARCH ARM TEST; RANDOMIZED CONTROLLED-TRIAL; INDUCED MOVEMENT THERAPY; FUGL-MEYER ASSESSMENT; STANDARDIZED APPROACH; ASSISTED THERAPY; MOTOR FUNCTION; REHABILITATION; HEMIPARESIS AB There is a great need to develop new approaches for rehabilitation of the upper limb after stroke. Robotic therapy is a promising form of neurorehabilitation that can be delivered in higher doses than conventional therapy. Here we sought to determine whether the reported effects of robotic therapy, which have been based on clinical measures of impairment and function, are accompanied by improved motor control. Patients with chronic hemiparesis were trained for 3 wk, 3 days a week, with titrated assistive robotic therapy in two and three dimensions. Motor control improvements (i.e., skill) in both arms were assessed with a separate untrained visually guided reaching task. We devised a novel PCA-based analysis of arm trajectories that is sensitive to changes in the quality of entire movement trajectories without needing to prespecify particular kinematic features. Robotic therapy led to skill improvements in the contralesional arm. These changes were not accompanied by changes in clinical measures of impairment or function. There are two possible interpretations of these results. One is that robotic therapy only leads to small task-specific improvements in motor control via normal skill-learning mechanisms. The other is that kinematic assays are more sensitive than clinical measures to a small general improvement in motor control. C1 [Kitago, Tomoko; Harran, Michelle; Kane, Leslie; Berard, Jessica; Huang, Sylvia; Ryan, Sophia L.; Mazzoni, Pietro; Krakauer, John W.; Huang, Vincent S.] Columbia Univ, Coll Phys & Surg, Dept Neurol, New York, NY USA. [Goldsmith, Jeff] Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA. [Ryan, Sophia L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Krakauer, John W.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Krakauer, John W.] Johns Hopkins Univ, Dept Neurosci, Baltimore, MD USA. RP Kitago, T (reprint author), 710 168th St, New York, NY 10032 USA. EM tk2229@columbia.edu FU National Institutes of Health [K02 NS048099]; Orentreich Family Foundation FX This work was supported by National Institutes of Health K02 NS048099 (J. W. Krakauer) and the Orentreich Family Foundation (J. W. Krakauer). NR 51 TC 11 Z9 11 U1 4 U2 10 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP 1 PY 2015 VL 114 IS 3 BP 1885 EP 1894 DI 10.1152/jn.00336.2015 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA CS4KQ UT WOS:000362045100048 PM 26180120 ER PT J AU Upah, R Jacob, T Price, RK AF Upah, Roxanne Jacob, Theodore Price, Rumi Kato TI Trajectories of Lifetime Comorbid Alcohol and Other Drug Use Disorders Through Midlife SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; DSM-IV ALCOHOL; DEVELOPMENTAL TRAJECTORIES; DRINKING TRAJECTORIES; EPIDEMIOLOGIC SURVEY; VIETNAM VETERANS; MIXTURE MODEL; DEPENDENT MEN; SUBSTANCE USE; ABUSE AB Objective: Very few studies have examined the developmental nature of comorbid alcohol use disorders and drug use disorders (AUD-DUD). The current study sought to extend our understanding of the nature of AUD-DUD comorbidity by characterizing the developmental course of AUD-DUD comorbidity, determining the degree to which the two disorders occur during the same period, and eliciting differences in AUD-DUD trajectories over the life course. Method: Vietnam-era male veterans and matched civilians provided retrospective accounts of alcohol- and other drug related experiences spanning 25 years. Concurrent growth mixture modeling was used to describe the course of AUD-DUD lifetime comorbidity. Results: Five trajectories were identified based on the probabilities of diagnosing with AUD-DUD: substance switching (increasing AUD, decreasing DUD); young adult (both AUD and DUD decreasing rapidly after young adulthood); severe nonchronic (both ADD and DUD decreasing slowly in the third decade of life); severe chronic alcohol severe nonchronic drug (AUD remains high and DUD decreases in the fourth decade); and young adult alcohol severe chronic drug (decreasing ADD in the second decade and DUD remains high). Conclusions: For the majority of this sample, substance use disorders continued or worsened through adulthood, indicating a problem that extends far beyond young adulthood. Demographic characteristics differed among the trajectories; however, psychiatric diagnoses did not differ except for the number of years with diagnoses of antisocial personality disorder. Subthreshold symptoms in adulthood may be present for a significant period before diagnosis, making this period important for intervention and prevention. Integration of efforts into healthcare, employment, and public policy will help target those at highest risk. C1 [Upah, Roxanne; Jacob, Theodore] Vet Affairs Palo Alto Healthcare Syst, Family Res Ctr, Menlo Pk, CA USA. [Price, Rumi Kato] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. RP Upah, R (reprint author), Oxnard Community Based Outpatient Clin, Vet Affairs Greater Los Angeles Healthcare Syst, 1690 Universe Circle, Oxnard, CA 93033 USA. EM roxanne.upah@va.gov FU Veterans Affairs Merit Award FX This research was supported by a Veterans Affairs Merit Award to Theodore Jacob. The opinions expressed here are the authors' and do not necessarily represent the views of the Department of Veterans Affairs. NR 49 TC 1 Z9 1 U1 2 U2 2 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 1937-1888 EI 1938-4114 J9 J STUD ALCOHOL DRUGS JI J. Stud. Alcohol Drugs PD SEP PY 2015 VL 76 IS 5 BP 721 EP 732 PG 12 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA CS4OQ UT WOS:000362055800007 PM 26402352 ER PT J AU Anderlini, P Wu, J Gersten, I Ewell, M Tolar, J Antin, JH Adams, R Arai, S Eames, G Horwitz, ME McCarty, J Nakamura, R Pulsipher, MA Rowley, S Leifer, E Carter, SL DiFronzo, NL Horowitz, MM Confer, D Deeg, HJ Eapen, M AF Anderlini, Paolo Wu, Juan Gersten, Iris Ewell, Marian Tolar, Jakob Antin, Joseph H. Adams, Roberta Arai, Sally Eames, Gretchen Horwitz, Mitchell E. McCarty, John Nakamura, Ryotaro Pulsipher, Michael A. Rowley, Scott Leifer, Eric Carter, Shelly L. DiFronzo, Nancy L. Horowitz, Mary M. Confer, Dennis Deeg, H. Joachim Eapen, Mary TI Cyclophosphamide conditioning in patients with severe aplastic anaemia given unrelated marrow transplantation: a phase 1-2 dose de-escalation study SO LANCET HAEMATOLOGY LA English DT Article ID STEM-CELL TRANSPLANTATION; ALTERNATIVE DONOR TRANSPLANTS; TOTAL-BODY IRRADIATION; SAA WORKING PARTY; BONE-MARROW; ANTITHYMOCYTE GLOBULIN; FLUDARABINE; TOXICITY; FAILURE; REGIMEN AB Background The optimum preparative regimen for unrelated donor marrow transplantation in patients with severe aplastic anaemia remains to be established. We investigated whether the combination of fludarabine, anti-thymocyte globulin, and total body irradiation (TBI) would enable reduction of the cyclophosphamide dose to less than 200 mg/kg while maintaining engraftment and having a survival similar to or better than that with standard regimens using a cyclophosphamide dose of 200 mg/kg (known to be associated with significant organ toxicity) for unrelated donor transplantation for severe aplastic anaemia. We have previously shown that cyclophosphamide at 150 mg/kg resulted in excess toxicity and its omission (0 mg/kg) resulted in unacceptable graft failure (three of three patients had secondary graft failure). Here we report results for the 50 mg/kg and 100 mg/kg cohorts. Methods In a multicentre phase 1-2 study, patients (aged <= 65 years) with severe aplastic anaemia, adequate organ function, and an unrelated adult marrow donor HLA matched at the allele level for HLA A, B, C, and DRB1 or mismatched at a single HLA locus received bone marrow grafts from unrelated donors. All patients received anti-thymocyte globulin (rabbit derived 3 mg/kg per day, intravenously, on days -4 to -2, or equine derived 30 mg/kg per day, intravenously, on days -4 to -2), fludarabine (30 mg/m.per day, intravenously, on days -5 to -2), and TBI (2 Gy). Cyclophosphamide dosing started at 150 mg/kg and was de-escalated in steps of 50 mg/kg (to 100 mg/kg, 50 mg/kg, and 0 mg/kg). The primary endpoint was the selection of the optimum cyclophosphamide dose based on assessments of graft failure (primary or secondary), toxicity, and early death during 100 days of follow-up after the transplant; this is the planned final analysis for the primary endpoint. This trial is registered with ClinicalTrials.gov, number NCT00326417. Findings 96 patients had bone marrow transplant. At day 100, 35 (92%) of 38 patients were engrafted and alive in the cyclophosphamide 50 mg/kg cohort and 35 (85%) of 41 in the 100 mg/kg cohort. Cyclophosphamide 50 mg/kg and 100 mg/kg resulted in posterior means for fatality without graft failure of 0.7% (credible interval 0-3.3) and 1.4% (0-4.9), respectively. Three patients (8%) had graft failure with cyclophosphamide 50 mg/kg and six (15%) with cyclophosphamide 100 mg/kg. Four (11%) patients had major regimen-related toxicity with cyclophosphamide 50 mg/kg and nine (22%) with cyclophosphamide 100 mg/kg. The most common organ toxicity was pulmonary (grade 3 or 4 dyspnoea or hypoxia including mechanical ventilation), and occurred in three (8%) and four (10%) patients given cyclophosphamide 50 mg/kg and 100 mg/kg, respectively. Interpretation Cyclophosphamide at 50 mg/kg and 100 mg/kg with TBI 2 Gy, fludarabine, and anti-thymocyte globulin results in effective conditioning and few early deaths after unrelated donor transplantation for severe aplastic anaemia. These doses of cyclophosphamide provide a framework for further regimen optimisation strategies. C1 [Anderlini, Paolo] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Wu, Juan; Gersten, Iris; Ewell, Marian; Carter, Shelly L.] Emmes Corp, Rockville, MD USA. [Tolar, Jakob] Univ Minnesota, Minneapolis, MN USA. [Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Adams, Roberta] Phoenix Childrens Hosp, Phoenix, AZ USA. [Arai, Sally] Stanford Hosp & Clin, Stanford, CA USA. [Eames, Gretchen] Cooks Childrens Hosp, Ft Worth, TX USA. [Horwitz, Mitchell E.] Duke Univ, Durham, NC USA. [McCarty, John] Virginia Commonwealth Univ, Richmond, VA USA. [Nakamura, Ryotaro] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Pulsipher, Michael A.] Univ Utah, Salt Lake City, UT USA. [Rowley, Scott] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Leifer, Eric; DiFronzo, Nancy L.] NHLBI, Bethesda, MD 20892 USA. [Horowitz, Mary M.; Eapen, Mary] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Confer, Dennis] Natl Marrow Donor Program, Minneapolis, MN USA. [Deeg, H. Joachim] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Anderlini, P (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Room FC5-3062,1515 Holcombe Blvd,Unit 0423, Houston, TX 77030 USA. EM panderli@mdanderson.org FU US National, Heart, Lung and Blood Institute [U10HL069294]; National Cancer Institute FX This trial was fully supported by grant number U10HL069294 from the US National, Heart, Lung and Blood Institute and the National Cancer Institute. EL and NLD are US Government employees (National Heart, Lung, and Blood Institute). We thank the clinical investigators who entered this study and managed patients; and Ellen Parker (Emmes Corporation, Rockville, MD, USA) for her assistance in the preparation of the manuscript. The findings reported in this paper are those of the authors. NR 31 TC 11 Z9 11 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2352-3026 J9 LANCET HAEMATOL JI Lancet Haematol. PD SEP PY 2015 VL 2 IS 9 BP E367 EP E375 PG 9 WC Hematology SC Hematology GA CS4VV UT WOS:000362075100007 PM 26685770 ER PT J AU Halgren, E Kaestner, E Marinkovic, K Cash, SS Wang, C Schomer, DL Madsen, JR Ulbert, I AF Halgren, Eric Kaestner, Erik Marinkovic, Ksenija Cash, Sydney S. Wang, Chunmao Schomer, Donald L. Madsen, Joseph R. Ulbert, Istvan TI Laminar profile of spontaneous and evoked theta: Rhythmic modulation of cortical processing during word integration SO NEUROPSYCHOLOGIA LA English DT Article DE Entorhinal; Inferotemporal; Prefrontal; Perirhinal; Cingulate; Feedforward; Feedback; Current-source density; Gamma; Delta ID HUMAN NEOCORTICAL OSCILLATIONS; ANTEROVENTRAL TEMPORAL-LOBE; DEPTH-RECORDED POTENTIALS; WORKING-MEMORY TASK; RAT VISUAL-CORTEX; HIPPOCAMPAL THETA; PERIRHINAL CORTEX; NEURONAL-ACTIVITY; CEREBRAL-CORTEX; CORTICOCORTICAL CONNECTIONS AB Theta may play a central role during language understanding and other extended cognitive processing, providing an envelope for widespread integration of participating cortical areas. We used linear microelectrode arrays in epileptics to define the circuits generating theta in inferotemporal, perirhinal, entorhinal, prefrontal and anterior cingulate cortices. In all locations, theta was generated by excitatory current sinks in middle layers which receive predominantly feedforward inputs, alternating with sinks in superficial layers which receive mainly feedback/associative inputs. Baseline and event-related theta were generated by indistinguishable laminar profiles of transmembrane currents and unit-firing. Word presentation could reset theta phase, permitting theta to contribute to late event-related potentials, even when theta power decreases relative to baseline. Limited recordings during sentence reading are consistent with rhythmic theta activity entrained by a given word modulating the neural background for the following word. These findings show that theta occurs spontaneously, and can be momentarily suppressed, reset and synchronized by words. Theta represents an alternation between feedforward/divergent and associative/convergent processing modes that may temporally organize sustained processing and optimize the timing of memory formation. We suggest that words are initially encoded via a ventral feedforward stream which is lexicosemantic in the anteroventral temporal lobe; its arrival may trigger a widespread theta rhythm which integrates the word within a larger context. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Halgren, Eric; Wang, Chunmao] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92069 USA. [Halgren, Eric; Wang, Chunmao] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92069 USA. [Kaestner, Erik; Wang, Chunmao] Univ Calif San Diego, Interdepartmental Neurosci Program, La Jolla, CA 92069 USA. [Marinkovic, Ksenija; Wang, Chunmao] San Diego State Univ, Dept Psychol, San Diego, CA 92182 USA. [Cash, Sydney S.; Wang, Chunmao] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02129 USA. [Wang, Chunmao; Schomer, Donald L.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA. [Wang, Chunmao; Madsen, Joseph R.] Harvard Univ, Sch Med, Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Wang, Chunmao; Ulbert, Istvan] Hungarian Acad Sci, Res Ctr Nat Sci, Inst Cognit Neurosci & Psychol, H-1117 Budapest, Hungary. RP Halgren, E (reprint author), Univ Calif San Diego, Dept Radiol, La Jolla, CA 92069 USA. EM ehalgren@ucsd.edu RI Ulbert, Istvan/F-2213-2010 FU ONR MURI [N00014-13-1-0672]; NIH [NS18741] FX We thank George Karmos, Howard Blume, Gary Heit, Qianqian Deng, Tristan Davenport, Lucia Melloni, Suresh Narayanan, Julian Wu, and Katherine Reid for their contributions to this research. Supported by ONR MURI N00014-13-1-0672 and NIH NS18741. NR 101 TC 2 Z9 2 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 EI 1873-3514 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD SEP PY 2015 VL 76 SI SI BP 108 EP 124 DI 10.1016/j.neuropsychologia.2015.03.021 PG 17 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA CS5QX UT WOS:000362134200010 PM 25801916 ER PT J AU Serena, G Camhi, S Sturgeon, C Yan, S Fasano, A AF Serena, Gloria Camhi, Stephanie Sturgeon, Craig Yan, Shu Fasano, Alessio TI The Role of Gluten in Celiac Disease and Type 1 Diabetes SO NUTRIENTS LA English DT Review DE celiac disease; type 1 diabetes; gluten ID INTESTINAL PERMEABILITY; ENTEROVIRUS INFECTIONS; ISLET AUTOIMMUNITY; TISSUE TRANSGLUTAMINASE; MICROBIOTA COMPOSITION; TYROSINE PHOSPHATASE; DIETARY INTERVENTION; SWEDISH CHILDREN; IMMUNE-RESPONSE; WHEAT GLUTEN AB Celiac disease (CD) and type 1 diabetes (T1D) are autoimmune conditions in which dietary gluten has been proven or suggested to play a pathogenic role. In CD; gluten is established as the instigator of autoimmunity; the autoimmune process is halted by removing gluten from the diet; which allows for resolution of celiac autoimmune enteropathy and subsequent normalization of serological markers of the disease. However; an analogous causative agent has not yet been identified for T1D. Nevertheless; the role of dietary gluten in development of T1D and the potentially beneficial effect of removing gluten from the diet of patients with T1D are still debated. In this review; we discuss the comorbid occurrence of CD and T1D and explore current evidences for the specific role of gluten in both conditions; specifically focusing on current evidence on the effect of gluten on the immune system and the gut microbiota. C1 [Serena, Gloria; Camhi, Stephanie; Sturgeon, Craig; Yan, Shu; Fasano, Alessio] Massachusetts Gen Hosp, Ctr Celiac Res, Mucosal Immunol & Biol Res Ctr, Boston, MA 02114 USA. [Serena, Gloria; Camhi, Stephanie; Sturgeon, Craig; Yan, Shu; Fasano, Alessio] Massachusetts Gen Hosp Children, Div Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. [Serena, Gloria; Sturgeon, Craig] Univ Maryland, Sch Med, Grad Program Life Sci, Baltimore, MD 21201 USA. RP Fasano, A (reprint author), Massachusetts Gen Hosp, Ctr Celiac Res, Mucosal Immunol & Biol Res Ctr, Boston, MA 02114 USA. EM gserena@mgh.harvard.edu; sscamhi@partners.org; csturgeon@mgh.harvard.edu; syan4@mgh.harvard.edu; afasano@mgh.harvard.edu NR 111 TC 5 Z9 5 U1 5 U2 19 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2072-6643 J9 NUTRIENTS JI Nutrients PD SEP PY 2015 VL 7 IS 9 BP 7143 EP 7162 DI 10.3390/nu7095329 PG 20 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CS2HI UT WOS:000361889400002 PM 26343710 ER PT J AU Moura, F Salles, J Hamdy, O Coutinho, W Baptista, DR Benchimol, A Marchetti, A Hegazi, RA Mechanick, JI AF Moura, Fabio Salles, Joao Hamdy, Osama Coutinho, Walmir Baptista, Deise Regina Benchimol, Alexander Marchetti, Albert Hegazi, Refaat A. Mechanick, Jeffrey I. TI Transcultural Diabetes Nutrition Algorithm: Brazilian Application SO NUTRIENTS LA English DT Article DE diabetes; prediabetes; obesity; nutrition therapy; physical exercise; algorithm; transcultural; Brazil; chronic non-communicable disease ID IMPAIRED GLUCOSE-TOLERANCE; PHYSICAL-ACTIVITY; GLYCEMIC CONTROL; POSITION STATEMENT; MEAL REPLACEMENTS; DIETARY SURVEY; UNITED-STATES; ENERGY-INTAKE; OLDER-ADULTS; MELLITUS AB The prevalence of obesity, pre-diabetes, and type 2 diabetes (T2D) is increasing worldwide, especially in the developing nations of South America. Brazil has experienced an exponential increase in the prevalence of these chronic non-communicable diseases. The rising prevalence is probably due to changing eating patterns, sedentary living, and a progressive aging of the population. These trends and their underlying causes carry untoward consequences for all Brazilians and the future of Brazilian public health and the healthcare system. Lifestyle changes that include healthy eating (nutrition therapy) and regular physical activity (structured exercise) represent efficient inexpensive measures to prevent and/or treat the aforementioned disorders and are recommended for all afflicted patients. Regrettably, the implementation of lifestyle changes is fraught with clinical and personal challenges in real life. The transcultural Diabetes Nutrition Algorithm (tDNA) is a therapeutic tool intended to foster implementation of lifestyle recommendations and to improve disease-related outcomes in common clinical settings. It is evidence-based and amenable to cultural adaptation. The Brazilian Diabetes Association, Society of Cardiology and Ministry of Health guidelines for nutrition therapy and physical exercise were considered for the Brazilian adaptation. The resultant tDNA-Brazil and its underlying recommendations are presented and explained. C1 [Moura, Fabio] Univ Pernambuco, Dept Endocrinol & Metab, BR-50100130 Recife, PE, Brazil. [Salles, Joao] Santa Sao Paulo Med Sch, Dept Internal Med, Endocrine Unit, BR-04119010 Sao Paulo, Brazil. [Hamdy, Osama] Harvard Univ, Joslin Diabet Ctr, Boston, MA 02215 USA. [Coutinho, Walmir] Catholic Univ, Dept Endocrinol, BR-22211340 Rio De Janeiro, Brazil. [Baptista, Deise Regina] Univ Fed Parana, Dept Nutr, BR-04566905 Curitiba, Parana, Brazil. [Benchimol, Alexander] State Inst Diabet & Endocrinol, BR-20211340 Rio De Janeiro, Brazil. [Marchetti, Albert] Rutgers New Jersey Med Sch, Dept Prevent Med & Community Hlth, Newark, NJ 07101 USA. [Hegazi, Refaat A.] Abbott Nutr, Res & Dev, Columbus, OH 43219 USA. [Mechanick, Jeffrey I.] Icahn Sch Med Mt Sinai, Div Endocrinol Diabet & Bone Dis, New York, NY 10029 USA. RP Moura, F (reprint author), Univ Pernambuco, Dept Endocrinol & Metab, BR-50100130 Recife, PE, Brazil. EM fmoura.pe@gmail.com; jensalles@yahoo.com.br; osama.hamdy@joslin.harvard.edu; wcoutinho@globo.com; deiseregina@ufpr.br; alexanderbenchimol@rjnet.com.br; albertmarchetti@yahoo.com; refaat.hegazi@abbott.com; jeffreymechanick@gmail.com FU Abbott Nutrition Research and Development FX The authors wish to thank Abbott Nutrition Research and Development for funding the development of this manuscript. NR 70 TC 3 Z9 3 U1 2 U2 5 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2072-6643 J9 NUTRIENTS JI Nutrients PD SEP PY 2015 VL 7 IS 9 BP 7358 EP 7380 DI 10.3390/nu7095342 PG 23 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CS2HI UT WOS:000361889400016 PM 26340638 ER PT J AU Nagayama, K Morino, K Sekine, O Nakagawa, F Ishikado, A Iwasaki, H Okada, T Tawa, M Sato, D Imamura, T Nishio, Y Ugi, S Kashiwagi, A Okamura, T Maegawa, H AF Nagayama, Kohji Morino, Katsutaro Sekine, Osamu Nakagawa, Fumiyuki Ishikado, Atsushi Iwasaki, Hirotaka Okada, Takashi Tawa, Masashi Sato, Daisuke Imamura, Takeshi Nishio, Yoshihiko Ugi, Satoshi Kashiwagi, Atsunori Okamura, Tomio Maegawa, Hiroshi TI Duality of n-3 Polyunsaturated Fatty Acids on Mcp-1 Expression in Vascular Smooth Muscle: A Potential Role of 4-Hydroxy Hexenal SO NUTRIENTS LA English DT Article DE monocyte chemotactic protein 1; 4-hydroxy hexenal; docosahexaenoic acid; eicosapentaenoic acid ID CORONARY-HEART-DISEASE; DOCOSAHEXAENOIC ACID; EICOSAPENTAENOIC ACID; ENDOTHELIAL FUNCTION; HEME OXYGENASE-1; CELLS; PATHWAY; FISH; ATHEROSCLEROSIS; INFLAMMATION AB N-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have protective effects against atherosclerosis. Monocyte chemotactic protein (MCP)-1 is a major inflammatory mediator in the progression of atherosclerosis. However, little is known about the regulation of Mcp-1 by DHA and EPA in vessels and vascular smooth muscle cells (VSMCs). In this study, we compared the effect of DHA and EPA on the expression of Mcp-1 in rat arterial strips and rat VSMCs. DHA, but not EPA, suppressed Mcp-1 expression in arterial strips. Furthermore, DHA generated 4-hydroxy hexenal (4-HHE), an end product of n-3 polyunsaturated fatty acids (PUFAs), in arterial strips as measured by liquid chromatography-tandem mass spectrometry. In addition, 4-HHE treatment suppressed Mcp-1 expression in arterial strips, suggesting 4-HHE derived from DHA may be involved in the mechanism of this phenomenon. In contrast, Mcp-1 expression was stimulated by DHA, EPA and 4-HHE through p38 kinase and the Keap1-Nuclear factor erythroid-derived 2-like 2 (Nrf2) pathway in VSMCs. In conclusion, there is a dual effect of n-3 PUFAs on the regulation of Mcp-1 expression. Further study is necessary to elucidate the pathological role of this phenomenon. C1 [Nagayama, Kohji; Morino, Katsutaro; Sekine, Osamu; Nakagawa, Fumiyuki; Ishikado, Atsushi; Iwasaki, Hirotaka; Okada, Takashi; Sato, Daisuke; Ugi, Satoshi; Maegawa, Hiroshi] Shiga Univ Med Sci, Dept Med, Otsu, Shiga 5202192, Japan. [Nakagawa, Fumiyuki] JCL Bioassay Corp, Osaka Lab, Suita, Osaka 5640043, Japan. [Ishikado, Atsushi] Sunstar Inc, Takatsuki, Osaka 5691195, Japan. [Ishikado, Atsushi] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Iwasaki, Hirotaka; Tawa, Masashi; Imamura, Takeshi; Okamura, Tomio] Shiga Univ Med Sci, Dept Pharmacol, Otsu, Shiga 5202192, Japan. [Nishio, Yoshihiko] Kagoshima Univ, Dept Diabet & Endocrine Med, Kagoshima 8908580, Japan. [Kashiwagi, Atsunori] Kusatsu Gen Hosp, Kusatsu, Shiga 5258585, Japan. RP Morino, K (reprint author), Shiga Univ Med Sci, Dept Med, Otsu, Shiga 5202192, Japan. EM nagayama@belle.shiga-med.ac.jp; morino@belle.shiga-med.ac.jp; sekine@belle.shiga-med.ac.jp; f.nakagawa@jclbio.com; atsushi.ishikado@jp.sunstar.com; hiwasaki@belle.shiga-med.ac.jp; tokada@belle.shiga-med.ac.jp; tawa@belle.shiga-med.ac.jp; dkst0310@belle.shiga-med.ac.jp; timamura@belle.shiga-med.ac.jp; ynishio@m3.kufm.kagoshima-u.ac.jp; sugi@belle.shiga-med.ac.jp; kashiwagi@kusatsu-gh.or.jp; okamura@belle.shiga-med.ac.jp; maegawa@belle.shiga-med.ac.jp FU Shiga University of Medical Science; Astellas Pharma; AstraZeneca; Boehringer-Mannheim; Daiichi-Sankyo; Dainippon-Sumitomo Pharma; MSD; Kowa; Sunstar; Takeda Pharmaceutical Company; Mitsubishi-Tanabe Pharma Corporation; Novartis; Novo Nordisk; Kyowa-Hakko-Kirin; Taisho-Toyama; Teijin Pharma; Ministry of Education, Culture, Sports, Science and Technology of Japan [23591336] FX We thank Chisato Kusunoki, Megumi Matsuo, Keiko Kosaka and Keiko Kondo for their technical help. Sources of founding: this study was funded by Shiga University of Medical Science. The Department of Medicine, Shiga University of Medical Science receives research promotion grants (Shogaku Kifukin) from Astellas Pharma, AstraZeneca, Boehringer-Mannheim, Daiichi-Sankyo, Dainippon-Sumitomo Pharma, MSD, Kowa, Sunstar, Takeda Pharmaceutical Company, Mitsubishi-Tanabe Pharma Corporation, Novartis, Novo Nordisk, Kyowa-Hakko-Kirin, Taisho-Toyama, Teijin Pharma. However, the research topics of these grants are not restricted. This work was supported in part by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan to Y. Nishio (#23591336). This study was performed in collaboration between Shiga University of Medical Science and JCL Bioassay Corporation. F. Nakagawa is an employee of JCL Bioassay Corporation and a graduate student at Shiga University of Medical Science; however, this does not alter the authors' adherence to all of the policies of Nutrients regarding the sharing of data and materials. NR 35 TC 1 Z9 1 U1 0 U2 0 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2072-6643 J9 NUTRIENTS JI Nutrients PD SEP PY 2015 VL 7 IS 9 BP 8112 EP 8126 DI 10.3390/nu7095381 PG 15 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CS2HI UT WOS:000361889400057 PM 26402697 ER PT J AU Wright, J Bellon, JR AF Wright, Jean Bellon, Jennifer R. TI Should Response to Preoperative Therapy Guide Local Management in Node-Positive Breast Cancer? SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID SURGICAL ADJUVANT BREAST; NEOADJUVANT CHEMOTHERAPY; RECURRENCE; WOMEN; EFFICACY; IMPACT; B-18; B-27 C1 [Wright, Jean] Johns Hopkins Univ, Dept Radiat Oncol & Mol Radiat Sci, Baltimore, MD 21218 USA. [Bellon, Jennifer R.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Bellon, Jennifer R.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Wright, J (reprint author), Johns Hopkins Univ, Dept Radiat Oncol & Mol Radiat Sci, Baltimore, MD 21218 USA. NR 13 TC 0 Z9 0 U1 1 U2 1 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD SEP PY 2015 VL 29 IS 9 BP 667 EP 668 PG 2 WC Oncology SC Oncology GA CS4PE UT WOS:000362057200010 PM 26384803 ER PT J AU Metcalfe, JZ O'Donnell, MR Bangsberg, DR AF Metcalfe, John Z. O'Donnell, Max R. Bangsberg, David R. TI Moving Beyond Directly Observed Therapy for Tuberculosis SO PLOS MEDICINE LA English DT Editorial Material ID DRUG-RESISTANCE; PULMONARY TUBERCULOSIS; TREATMENT ADHERENCE; EMERGENCE; RIFAMPIN; TB C1 [Metcalfe, John Z.] Univ Calif San Francisco, San Francisco Gen Hosp, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA. [O'Donnell, Max R.] Columbia Univ Med Ctr, Div Pulm Allergy & Crit Care Med, New York, NY USA. [Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Sch Publ Hlth, Boston, MA 02115 USA. [Bangsberg, David R.] Mbarara Univ Sci & Technol, Mbarara, Uganda. RP Metcalfe, JZ (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA. EM john.metcalfe@ucsf.edu NR 24 TC 4 Z9 4 U1 0 U2 2 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 SEP PY 2015 VL 12 IS 9 AR e1001877 DI 10.1371/journal.pmed.1001877 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA CS6TU UT WOS:000362216200005 PM 26372602 ER PT J AU Morris, E Feig, SA Drexler, M Lehman, C AF Morris, Elizabeth Feig, Stephen A. Drexler, Madeline Lehman, Constance TI Implications of Overdiagnosis: Impact on Screening Mammography Practices SO POPULATION HEALTH MANAGEMENT LA English DT Review ID BREAST-CANCER INCIDENCE; ENGLAND-JOURNAL-OF; CARCINOMA IN-SITU; DIGITAL MAMMOGRAPHY; FOLLOW-UP; TOMOSYNTHESIS; TRIAL; MORTALITY; RECOMMENDATIONS; OVERTREATMENT AB This review article explores the issue of overdiagnosis in screening mammography. Overdiagnosis is the screen detection of a breast cancer, histologically confirmed, that might not otherwise become clinically apparent during the lifetime of the patient. While screening mammography is an imperfect tool, it remains the best tool we have to diagnose breast cancer early, before a patient is symptomatic and at a time when chances of survival and options for treatment are most favorable. In 2015, an estimated 231,840 new cases of breast cancer (excluding ductal carcinoma in situ) will be diagnosed in the United States, and some 40,290 women will die. Despite these data, screening mammography for women ages 40-69 has contributed to a substantial reduction in breast cancer mortality, and organized screening programs have led to a shift from late-stage diagnosis to early-stage detection. Current estimates of overdiagnosis in screening mammography vary widely, from 0% to upwards of 30% of diagnosed cancers. This range reflects the fact that measuring overdiagnosis is not a straightforward calculation, but usually one based on different sets of assumptions and often biased by methodological flaws. The recent development of tomosynthesis, which creates high-resolution, three-dimensional images, has increased breast cancer detection while reducing false recalls. Because the greatest harm of overdiagnosis is overtreatment, the key goal should not be less diagnosis but better treatment decision tools. (Population Health Management 2015;18:S3-S11) C1 [Morris, Elizabeth] Mem Sloan Kettering Canc Ctr, Breast Imaging Serv, New York, NY 10021 USA. [Morris, Elizabeth] Weill Cornell Med Coll, Dept Radiol, New York, NY USA. [Feig, Stephen A.] Univ Calif Irvine, Med Ctr, Dept Radiol, Irvine, CA USA. [Feig, Stephen A.] Univ Calif Irvine, Sch Med, Dept Womens Imaging, Irvine, CA 92717 USA. [Drexler, Madeline] Harvard Univ, TH Chan Sch Publ Hlth, Harvard Publ Hlth, Boston, MA 02115 USA. [Lehman, Constance] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Lehman, C (reprint author), Massachusetts Gen Hosp, Dept Radiol, Breast Imaging, 55 Fruit St, Boston, MA 02114 USA. EM clehman@partners.org FU Mary Ann Liebert, Inc.; GE; Hologic FX Ms. Drexler is employed by the Harvard T.H. Chan School of Public Health and received financial support from Mary Ann Liebert, Inc., publishers, to review the literature, consult with designated experts, and develop and coauthor this article. Drs. Morris, Feig, and Lehman received an honorarium from Mary Ann Liebert, Inc., publishers for their participation in this article. Dr. Morris has nothing to disclose. Dr. Feig was a consultant to Hologic, Inc., from 2007 to 2014. Dr. Lehman serves on the medical advisory board for GE Healthcare and has received research funding from GE. The article was made possible by an educational grant to the Publisher from Hologic. NR 55 TC 5 Z9 5 U1 0 U2 10 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1942-7891 EI 1942-7905 J9 POPUL HEALTH MANAG JI Popul. Health Manag. PD SEP 1 PY 2015 VL 18 SU 1 SI SI BP S3 EP S11 DI 10.1089/pop.2015.29023.mor PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CS2HA UT WOS:000361888600001 PM 26414384 ER PT J AU Ortiz, AE Avram, MM AF Ortiz, Arisa E. Avram, Mathew M. TI Noninvasive body contouring: cryolipolysis and ultrasound SO SEMINARS IN CUTANEOUS MEDICINE AND SURGERY LA English DT Article ID INTENSITY FOCUSED ULTRASOUND; SUBCUTANEOUS ADIPOSE-TISSUE; SAFETY; EFFICACY; REDUCTION; DEVICE; LASER AB Over the past 5 years, there has been a paradigm shift in the treatment of fat, The clear trend is toward noninvasive fat removal technologies over more traditional forms of fat removal such as liposuction. While these devices do not yet approach the results seen with liposuction, noninvasive treatments are gaining popularity due to their ability to safely and effectively reduce fat with little downtime and typically no need for anesthesia. The optimal candidate is relatively fit with localized areas of adiposity, rather than an obese patient. It is important to note that there are numerous noninvasive fat devices including low-level light, radiofrequency, laser, cryolipolysis, and ultrasound. Some of these technologies have more robust data to support their efficacy than others. This review will focus on only 2 noninvasive fat technologies: cryolipolysis and ultrasound. (C) 2015 Frontline Medical Communications C1 [Ortiz, Arisa E.] Univ Calif San Diego, Dept Dermatol, Laser & Cosmet Dermatol, San Diego, CA 92122 USA. [Avram, Mathew M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dermatol Laser & Cosmet Ctr, Boston, MA USA. [Avram, Mathew M.] Wellman Ctr Photomed, Boston, MA USA. RP Ortiz, AE (reprint author), Univ Calif San Diego, Cosmet & Laser Dermatol, 8899 Univ Ctr Ln,350, San Diego, CA 92122 USA. EM arisaortiz@gmail.com NR 29 TC 0 Z9 0 U1 4 U2 6 PU FRONTLINE MEDICAL COMMUNICATIONS PI THE WOODLANDS PA WRIGHTS MEDIA, 2407 TIMBERLOCH PLACE, SUITE B, THE WOODLANDS, TX 77386 USA SN 1085-5629 EI 1558-0768 J9 SEMIN CUTAN MED SURG JI Semin. Cutan. Med. Surg. PD SEP PY 2015 VL 34 IS 3 BP 129 EP 133 PG 5 WC Dermatology; Surgery SC Dermatology; Surgery GA CS2WS UT WOS:000361933300003 PM 26566568 ER PT J AU Wang, R Szabo, C Ichinose, F Ahmed, A Whiteman, M Papapetropoulos, A AF Wang, Rui Szabo, Csaba Ichinose, Fumito Ahmed, Asif Whiteman, Matthew Papapetropoulos, Andreas TI The role of H2S bioavailability in endothelial dysfunction SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review DE cystathionine gamma-lyase; endothelium-derived hyperpolarizing factor; gasotransmitters; heme oxygenase-1; hydrogen sulfide; nitric oxide ID CYSTATHIONINE GAMMA-LYASE; NITRIC-OXIDE SYNTHASE; HYDROGEN-SULFIDE DONOR; OXIDATIVE STRESS; HYPERPOLARIZING FACTOR; ENDOGENOUS PRODUCTION; VASCULAR DYSFUNCTION; CEREBRAL-ISCHEMIA; S-SULFHYDRATION; UP-REGULATION AB Endothelial dysfunction (EDF) reflects pathophysiological changes in the phenotype and functions of endothelial cells that result from and/or contribute to a plethora of cardiovascular diseases. We review the role of hydrogen sulfide (H2S) in the pathogenesis of EDF, one of the fastest advancing research topics. Conventionally treated as an environment pollutant, H2S is also produced in endothelial cells and participates in the fine regulation of endothelial integrity and functions. Disturbed H2S bioavailability has been suggested to be a novel indicator of EDF progress and prognosis. EDF manifests in different forms in multiple pathologies, but therapeutics aimed at remedying altered H2S bioavailability may benefit all. C1 [Wang, Rui] Laurentian Univ, Dept Biol, Sudbury, ON P3E 2C6, Canada. [Szabo, Csaba] Univ Texas Med Branch, Dept Anesthesiol, Galveston, TX 77555 USA. [Ichinose, Fumito] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Ahmed, Asif] Aston Univ, Aston Med Sch, Aston Med Res Inst, Birmingham B4 7ET, W Midlands, England. [Whiteman, Matthew] Univ Exeter, Sch Med, Exeter EX1 2LU, Devon, England. [Papapetropoulos, Andreas] Univ Athens, Fac Pharm, Athens 15771, Greece. [Papapetropoulos, Andreas] Univ Athens, Evangelismos Hosp, Dept Pulm & Crit Care Med 1, George P Livanos & Marianthi Simou Labs,Fac Med, Athens 10675, Greece. RP Wang, R (reprint author), Laurentian Univ, Dept Biol, 935 Ramsey Lake Rd, Sudbury, ON P3E 2C6, Canada. EM rui.wang@laurentian.ca RI Whiteman, Matthew/C-6079-2009 OI Whiteman, Matthew/0000-0002-6583-6779 FU Discovery Grant from the Natural Sciences and Engineering Research Council of Canada (NSERC); American Diabetes Association; US National Institutes of Health (NIH); Shriners Hospitals for Children; NIH; UK Medical Research Council (MEC); British Heart Foundation [RG/09/001/25940]; MRC [G0700288]; Royal Society; European Commission; Aristeia grant [1436]; European Commission (ESF); Greek national funds through the Operational Program 'Education and Lifelong Learning'; COST (Cooperation in Science and Technology) Action [BM1005] FX This work has been supported by a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada (NSERC) to R.W. C.S. has been supported by the American Diabetes Association, the US National Institutes of Health (NIH), and the Shriners Hospitals for Children. F.I. has been supported by the NIH. MW has been supported by the UK Medical Research Council (MEC). A.A. has been supported by program grants from the British Heart Foundation (RG/09/001/25940), MRC (G0700288), Royal Society, and the European Commission. A.P. has been supported through an Aristeia grant (1436) that is co-financed by the European Commission (ESF) and Greek national funds through the Operational Program 'Education and Lifelong Learning'. M.W. and A.P. are supported by the COST (Cooperation in Science and Technology) Action BM1005 (ENOG: European Network on Gasotransmitters). NR 103 TC 19 Z9 19 U1 7 U2 27 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD SEP PY 2015 VL 36 IS 9 BP 568 EP 578 DI 10.1016/j.tips.2015.05.007 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CS2ST UT WOS:000361922700003 PM 26071118 ER PT J AU Desai, JV Cheng, SJ Ying, T Nguyen, MH Clancy, CJ Lanni, F Mitchell, AP AF Desai, Jigar V. Cheng, Shaoji Ying, Tammy Nguyen, M. Hong Clancy, Cornelius J. Lanni, Frederick Mitchell, Aaron P. TI Coordination of Candida albicans Invasion and Infection Functions by Phosphoglycerol Phosphatase Rhr2 SO PATHOGENS LA English DT Article DE Candida albicans; adherence; invasion; biofilm; intra-abdominal candidiasis; glycerol; turgor; infection; adhesin ID BIOFILM FORMATION; EPITHELIAL-CELLS; HOST; PENETRATION; ATTACHMENT; RESPONSES; CONTACT; PATHWAY; STRESS; GROWTH AB The Candida albicans RHR2 gene, which specifies a glycerol biosynthetic enzyme, is required for biofilm formation in vitro and in vivo. Prior studies indicate that RHR2 is ultimately required for expression of adhesin genes, such as ALS1. In fact, RHR2 is unnecessary for biofilm formation when ALS1 is overexpressed from an RHR2-independent promoter. Here, we describe two additional biological processes that depend upon RHR2: invasion into an abiotic substrate and pathogenicity in an abdominal infection model. We report here that abiotic substrate invasion occurs concomitantly with biofilm formation, and a screen of transcription factor mutants indicates that biofilm and hyphal formation ability correlates with invasion ability. However, analysis presented here of the rhr2/ mutant separates biofilm formation and invasion. We found that an rhr2/ mutant forms a biofilm upon overexpression of the adhesin gene ALS1 or the transcription factor genes BRG1 or UME6. However, the biofilm-forming strains do not invade the substrate. These results indicate that RHR2 has an adhesin-independent role in substrate invasion, and mathematical modeling argues that RHR2 is required to generate turgor. Previous studies have shown that abdominal infection by C. albicans has two aspects: infection of abdominal organs and persistence in abscesses. We report here that an rhr2/ mutant is defective in both of these infection phenotypes. We find here that overexpression of ALS1 in the mutant restores infection of organs, but does not improve persistence in abscesses. Therefore, RHR2 has an adhesin-independent role in abdominal infection, just as it does in substrate invasion. This report suggests that RHR2, through glycerol synthesis, coordinates adherence with host- or substrate-interaction activities that enable proliferation of the C. albicans population. C1 [Desai, Jigar V.; Lanni, Frederick; Mitchell, Aaron P.] Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA. [Cheng, Shaoji; Ying, Tammy] Univ Pittsburgh, Div Infect Dis, Dept Med, Pittsburgh, PA 15261 USA. [Nguyen, M. Hong] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA. [Clancy, Cornelius J.] VA Pittsburgh Healthcare Syst, Infect Dis Sect, Pittsburgh, PA 15261 USA. RP Mitchell, AP (reprint author), Carnegie Mellon Univ, Dept Biol Sci, 4400 Fifth Ave MI-200B, Pittsburgh, PA 15213 USA. EM jigarkumar.desai@nih.gov; sjc43@pitt.edu; tammythinks@gmail.com; mhn5@pitt.edu; cjc76@pitt.edu; lanni@andrew.cmu.edu; apm1@cmu.edu FU NIH [R01 AI067703]; Stupakoff Graduate Fellowship FX We thank Carol Woolford, Wenjie Xu, Katie Lagree and Saranna Fanning for helpful advice and comments on the manuscript, and Tatyana Aleynikova for technical support. This study was supported by NIH research grant R01 AI067703 (A.P.M.) and a Stupakoff Graduate Fellowship (J.V.D.). NR 45 TC 2 Z9 2 U1 0 U2 1 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2076-0817 J9 PATHOGENS JI Pathogens PD SEP PY 2015 VL 4 IS 3 BP 573 EP 589 DI 10.3390/pathogens4030573 PG 17 WC Microbiology SC Microbiology GA CS7MB UT WOS:000362266600009 PM 26213976 ER PT J AU Scott, JP DiLillo, D Maldonado, RC Watkins, LE AF Scott, Jillian Panuzio DiLillo, David Maldonado, Rosalita C. Watkins, Laura E. TI Negative Urgency and Emotion Regulation Strategy Use: Associations With Displaced Aggression SO AGGRESSIVE BEHAVIOR LA English DT Article ID INTIMATE PARTNER VIOLENCE; INDIVIDUAL-DIFFERENCES; EXTERNALIZING BEHAVIOR; COGNITIVE REAPPRAISAL; SOCIAL-CONSEQUENCES; DISTRESS TOLERANCE; 5-FACTOR MODEL; ALCOHOL-USE; HOT SAUCE; SUPPRESSION AB The numerous public health consequences of interpersonal aggression highlight the necessity of a comprehensive understanding of factors influencing its perpetration. This study examined direct and interactive associations between negative urgency and emotion regulation strategy use in predicting displaced aggression under conditions of negative mood. Participants were 197 male and female undergraduate students who were randomly assigned to employ either cognitive reappraisal or expressive suppression in response to a negative mood induction. Immediately afterwards, participants engaged in an analog displaced aggression task. Results revealed direct, positive associations between negative urgency and aggression. In addition, the use of suppression was associated with greater aggression than was the use of reappraisal alone. Counter to the hypothesis, there were no interactive effects between negative urgency and emotion regulation strategy use in predicting aggression. Findings suggest reducing negative urgency and use of suppression as potential intervention targets for individuals who engage in aggressive behavior. Aggr. Behav. 41:502-512, 2015. (C) 2015 Wiley Periodicals, Inc. C1 [Scott, Jillian Panuzio; DiLillo, David; Maldonado, Rosalita C.; Watkins, Laura E.] Univ Nebraska, Dept Psychol, Lincoln, NE 68588 USA. RP Scott, JP (reprint author), VA Boston Healthcare Syst, Psychol Serv 116B, 150 S Huntington Ave, Boston, MA 02130 USA. EM jillian.scott@va.gov NR 81 TC 5 Z9 5 U1 7 U2 24 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0096-140X EI 1098-2337 J9 AGGRESSIVE BEHAV JI Aggressive Behav. PD SEP-OCT PY 2015 VL 41 IS 5 BP 502 EP 512 DI 10.1002/ab.21588 PG 11 WC Behavioral Sciences; Psychology, Multidisciplinary SC Behavioral Sciences; Psychology GA CS1FP UT WOS:000361808600010 PM 25753818 ER PT J AU Wilde, EA Bouix, S Tate, DF Lin, AP Newsome, MR Taylor, BA Stone, JR Montier, J Gandy, SE Biekman, B Shenton, ME York, G AF Wilde, Elisabeth A. Bouix, Sylvain Tate, David F. Lin, Alexander P. Newsome, Mary R. Taylor, Brian A. Stone, James R. Montier, James Gandy, Samuel E. Biekman, Brian Shenton, Martha E. York, Gerald TI Advanced neuroimaging applied to veterans and service personnel with traumatic brain injury: state of the art and potential benefits SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Traumatic brain injury; Magnetic resonance imaging; Diffusion tensor imaging; fMRI; Positron emission tomography; Magnetic resonance spectroscopy; Veteran ID MAGNETIC-RESONANCE-SPECTROSCOPY; PROTON MR SPECTROSCOPY; POSTTRAUMATIC-STRESS-DISORDER; CEREBRAL-BLOOD-FLOW; DIFFUSE AXONAL INJURY; SPORTS-RELATED CONCUSSION; WHITE-MATTER ABNORMALITIES; AFGHANISTAN WAR VETERANS; MEDIAL TEMPORAL-LOBES; PITTSBURGH COMPOUND-B AB Traumatic brain injury (TBI) remains one of the most prevalent forms of morbidity among Veterans and Service Members, particularly for those engaged in the conflicts in Iraq and Afghanistan. Neuroimaging has been considered a potentially useful diagnostic and prognostic tool across the spectrum of TBI generally, but may have particular importance in military populations where the diagnosis of mild TBI is particularly challenging, given the frequent lack of documentation on the nature of the injuries and mixed etiologies, and highly comorbid with other disorders such as post-traumatic stress disorder, depression, and substance misuse. Imaging has also been employed in attempts to understand better the potential late effects of trauma and to evaluate the effects of promising therapeutic interventions. This review surveys the use of structural and functional neuroimaging techniques utilized in military studies published to date, including the utilization of quantitative fluid attenuated inversion recovery (FLAIR), susceptibility weighted imaging (SWI), volumetric analysis, diffusion tensor imaging (DTI), magnetization transfer imaging (MTI), positron emission tomography (PET), magnetoencephalography (MEG), task-based and resting state functional MRI (fMRI), arterial spin labeling (ASL), and magnetic resonance spectroscopy (MRS). The importance of quality assurance testing in current and future research is also highlighted. Current challenges and limitations of each technique are outlined, and future directions are discussed. C1 [Wilde, Elisabeth A.; Newsome, Mary R.; Taylor, Brian A.] Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. [Wilde, Elisabeth A.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Wilde, Elisabeth A.] Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA. [Wilde, Elisabeth A.; Newsome, Mary R.; Biekman, Brian] Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. [Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Dept Psychiat, Sch Med, Boston, MA 02115 USA. [Tate, David F.] Univ Missouri St Louis, Missouri Inst Mental Hlth, Berkeley, MO USA. [Lin, Alexander P.] Harvard Univ, Brigham & Womens Hosp, Ctr Clin Spect, Sch Med, Boston, MA 02115 USA. [Lin, Alexander P.; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Dept Radiol, Sch Med, Boston, MA 02115 USA. [Montier, James] Univ Virginia Hlth Syst, Dept Radiol & Med Imaging, Dept Neurol Surg, Charlottesville, VA USA. [Gandy, Samuel E.] Icahn Sch Med, Ctr Cognit Hlth, New York, NY USA. [Gandy, Samuel E.] Icahn Sch Med, NFL Neurol Ctr, New York, NY USA. [Gandy, Samuel E.] James J Peters VA Med Ctr, Div Neurol, New York, NY USA. [Shenton, Martha E.] Vet Affairs Boston Healthcare Syst, Dept Psychiat, Brockton Div, Brockton, MA USA. [York, Gerald] San Antonio Mil Med Ctr, Def Vet Brain Injury Ctr, Ft Sam Houston, TX USA. RP Wilde, EA (reprint author), Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. EM ewilde@bcm.edu RI Tate, David/I-3963-2013; OI Tate, David/0000-0003-0213-1920 FU US Department of Veterans Affairs; VA MERIT review grant program [1I01RX000684-01A2, 1I01RX001062-01A1, 1 I01 RX000928:]; VA SPIRE program [VA 1 I21RX001565, VA 1 I21RX001608]; Department of Defense Office of the Congressionally Directed Medical Research Programs (CDMRP) [W81XWH-10-1-0835, X81XWH-07-CC-CSDoD]; National Institutes of Health [R01-NS078337]; Telemedicine and Advanced Technology Research Center (TATRC) at the U.S. Army Medical Research and Material Command (USAMRMC) [W81XWH-13-2-0025]; United States Army Medical Research Acquisition Activity (USAMRAA) [W81XWH-09-2-0160]; Chronic Effects Neurotrauma Consortium (CENC) [PT108802-SC106187, 1W81XWH-13-2-0095]; Alzheimer's Drug Discovery Foundation FX The authors recognize the support of the US Department of Veterans Affairs (EAW, BAT, SG, MRN, MES, SG), the VA MERIT review grant program (1I01RX000684-01A2: SG, 1I01RX001062-01A1: EAW, MRN, and 1 I01 RX000928: MES, SB), and VA SPIRE program (VA 1 I21RX001565 BAT, and VA 1 I21RX001608 MRN); the Department of Defense Office of the Congressionally Directed Medical Research Programs (CDMRP) (W81XWH-10-1-0835: APL; X81XWH-07-CC-CSDoD: MES, SB), the National Institutes of Health (R01-NS078337: APL, MES, SB), Telemedicine and Advanced Technology Research Center (TATRC) at the U.S. Army Medical Research and Material Command (USAMRMC; W81XWH-13-2-0025: DFT), United States Army Medical Research Acquisition Activity (USAMRAA; W81XWH-09-2-0160: JRS, SG), the Chronic Effects Neurotrauma Consortium (CENC; PT108802-SC106187 and 1W81XWH-13-2-0095), and the Alzheimer's Drug Discovery Foundation (SG). We also wish to thank Rhonda O'Donovan for her assistance in manuscript preparation. NR 192 TC 7 Z9 7 U1 5 U2 20 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 EI 1931-7565 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD SEP PY 2015 VL 9 IS 3 BP 367 EP 402 DI 10.1007/s11682-015-9444-y PG 36 WC Neuroimaging SC Neurosciences & Neurology GA CR8LQ UT WOS:000361604300003 PM 26350144 ER PT J AU Cooper, DB Bunner, AE Kennedy, JE Balldin, V Tate, DF Eapen, BC Jaramillo, CA AF Cooper, Douglas B. Bunner, Anne E. Kennedy, Jan E. Balldin, Valerie Tate, David F. Eapen, Blessen C. Jaramillo, Carlos A. TI Treatment of persistent post-concussive symptoms after mild traumatic brain injury: a systematic review of cognitive rehabilitation and behavioral health interventions in military service members and veterans SO BRAIN IMAGING AND BEHAVIOR LA English DT Review DE Mild traumatic brain injury; Post-concussive syndrome; Cognitive rehabilitation; Posttraumatic stress disorder; Blast Injuries; Post-deployment; OEF/OIF; Psychoeducation; Psychotherapy ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; MULTIFAMILY GROUP TREATMENT; POSTCONCUSSIVE SYMPTOMS; RESIDENTIAL-TREATMENT; TREATMENT ADHERENCE; PROLONGED EXPOSURE; GOAL MANAGEMENT; HEAD-INJURY; PILOT AB Increased prevalence of traumatic brain injury (TBI) has been associated with service members and veterans who completed combat deployments in support of Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF). Management of persistent post-concussive symptoms (PCS) has been a challenge to healthcare providers throughout the Military and Veterans Healthcare Systems, as well as civilian healthcare providers, due in part to the chronic nature of symptoms, co-occurrence of behavioral health disorders such as depression, Posttraumatic Stress Disorder (PTSD), and substance use disorders, and fear of a potential stigma associated with psychiatric diagnoses and behavioral health treatment(s). This systematic review examined non-pharmacologic behavioral health interventions and cognitive rehabilitation interventions for PCS in military service members and veterans with a history of mild TBI (mTBI). Six electronic databases were searched with specific term limitations, identifying 121 citations. Ultimately, 19 articles met criteria for inclusion in this systematic review. Studies were broadly categorized into four subtypes: psychoeducational interventions, cognitive rehabilitation, psychotherapeutic approaches, and integrated behavioral health interventions for PCS and PTSD. The review provides an update of the empirical evidence for these four types of interventions for PCS in active duty service members and veterans. Recommendations for future research are discussed, including the need to expand and improve the limited evidence basis on how to manage persistent post-concussive symptoms in this population. C1 [Cooper, Douglas B.; Kennedy, Jan E.] San Antonio Mil Med Ctr MCHE MDU DVBIC, Def & Vet Brain Injury Ctr, Ft Sam Houston, TX 78234 USA. [Cooper, Douglas B.; Kennedy, Jan E.] San Antonio Mil Med Ctr, Dept Neurol, Ft Sam Houston, TX USA. [Bunner, Anne E.] Def & Vet Brain Injury Ctr, Bethesda, MD USA. [Balldin, Valerie] Univ Texas Hlth Sci Ctr San Antonio, Dept Neurol, San Antonio, TX 78229 USA. [Tate, David F.] Univ Missouri, Missouri Inst Mental Hlth, St Louis, MO 63121 USA. [Eapen, Blessen C.; Jaramillo, Carlos A.] South Texas Vet Hlth Care Syst, Polytrauma Rehabil Ctr, San Antonio, TX USA. RP Cooper, DB (reprint author), San Antonio Mil Med Ctr MCHE MDU DVBIC, Def & Vet Brain Injury Ctr, 3551 Roger Brooke Dr, Ft Sam Houston, TX 78234 USA. EM douglas.b.cooper.ctr@mail.mil RI Tate, David/I-3963-2013; OI Tate, David/0000-0003-0213-1920 NR 71 TC 4 Z9 4 U1 8 U2 24 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 EI 1931-7565 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD SEP PY 2015 VL 9 IS 3 BP 403 EP 420 DI 10.1007/s11682-015-9440-2 PG 18 WC Neuroimaging SC Neurosciences & Neurology GA CR8LQ UT WOS:000361604300004 PM 26330376 ER PT J AU Jaramillo, CA Cooper, DB Wang, CP Tate, DF Eapen, BC York, GE Pugh, MJ AF Jaramillo, Carlos A. Cooper, Douglas B. Wang, Chen-Pin Tate, David F. Eapen, Blessen C. York, Gerald E. Pugh, Mary Jo TI Subgroups of US IRAQ and Afghanistan veterans: associations with traumatic brain injury and mental health conditions SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Veterans; Iraq; Afghanistan; TBI; PTSD; Latent class analysis ID POSTTRAUMATIC-STRESS-DISORDER; PERSISTENT POSTCONCUSSIVE SYMPTOMS; ENDURING FREEDOM VETERANS; POLYTRAUMA-CLINICAL-TRIAD; SUBSTANCE USE DISORDERS; PTSD SYMPTOMS; WAR VETERANS; CHRONIC PAIN; OEF/OIF VETERANS; MILITARY SERVICE AB U. S. veterans of Iraq and Afghanistan are known to have a high prevalence of traumatic brain injury (TBI), posttraumatic stress disorder (PTSD), and depression, which are often comorbid and share many symptoms. Attempts to describe this cohort by single diagnoses have limited our understanding of the complex nature of this population. The objective of this study was to identify subgroups of Iraq and Afghanistan veterans (IAVs) with distinct compositions of symptoms associated with TBI, PTSD, and depression. Our cross-sectional, observational study included 303,716 IAVs who received care in the Veterans Health Administration in 2010-2011. Symptoms and conditions were defined using International Classification of Diseases, Ninth Revision codes and symptom-clusters were identified using latent class analysis. We identified seven classes with distinct symptom compositions. One class had low probability of any condition and low health care utilization (HCU) (48 %). Other classes were characterized by high probabilities of mental health comorbidities (14 %); chronic pain and sleep disturbance (20 %); headaches and memory problems (6 %); and auditory problems (2.5 %). Another class had mental health comorbidities and chronic pain (7 %), and the last had high probabilities of most symptoms examined (3 %). These last two classes had the highest likelihood of TBI, PTSD, and depression and were identified as high healthcare utilizers. There are subgroups of IAVs with distinct clusters of symptom that are meaningfully associated with TBI, PTSD, depression, and HCU. Additional studies examining these veteran subgroups could improve our understanding of this complex comorbid patient population. C1 [Jaramillo, Carlos A.; Eapen, Blessen C.] South Texas Vet Healthcare Syst ALMD, Polytrauma Rehabil Ctr, San Antonio, TX 78229 USA. [Cooper, Douglas B.; Tate, David F.; York, Gerald E.] San Antonio Mil Med Ctr, Def & Vet Brain Injury Ctr, San Antonio, TX USA. [Wang, Chen-Pin; Pugh, Mary Jo] South Texas Vet Hlth Care Syst, Res & Dev, San Antonio, TX 78229 USA. [Wang, Chen-Pin; Pugh, Mary Jo] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. RP Jaramillo, CA (reprint author), South Texas Vet Healthcare Syst ALMD, Polytrauma Rehabil Ctr, 7400 Merton Minter Blvd 11C6, San Antonio, TX 78229 USA. EM jaramilloc3@uthscsa.edu; douglas.b.cooper.ctr@mail.mil; wangc3@uthscsa.edu; dftatephd@mac.com; Blessen.Eapen2@va.gov; gerald.e.york4.mil@mail.mil; maryjo.pugh2@va.gov RI Tate, David/I-3963-2013; OI Tate, David/0000-0003-0213-1920; Pugh, Mary Jo/0000-0003-4196-7763 FU VA Health Services Research and Development [DHI 09-237] FX The study was funded by VA Health Services Research and Development (DHI 09-237). NR 53 TC 2 Z9 2 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 EI 1931-7565 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD SEP PY 2015 VL 9 IS 3 BP 445 EP 455 DI 10.1007/s11682-015-9402-8 PG 11 WC Neuroimaging SC Neurosciences & Neurology GA CR8LQ UT WOS:000361604300006 PM 25963862 ER PT J AU Boots, EA Schultz, SA Oh, JM Larson, J Edwards, D Cook, D Koscik, RL Dowling, MN Gallagher, CL Carlsson, CM Rowley, HA Bendlin, BB LaRue, A Asthana, S Hermann, BP Sager, MA Johnson, SC Okonkwo, OC AF Boots, Elizabeth A. Schultz, Stephanie A. Oh, Jennifer M. Larson, Jordan Edwards, Dorothy Cook, Dane Koscik, Rebecca L. Dowling, Maritza N. Gallagher, Catherine L. Carlsson, Cynthia M. Rowley, Howard A. Bendlin, Barbara B. LaRue, Asenath Asthana, Sanjay Hermann, Bruce P. Sager, Mark A. Johnson, Sterling C. Okonkwo, Ozioma C. TI Cardiorespiratory fitness is associated with brain structure, cognition, and mood in a middle-aged cohort at risk for Alzheimer's disease SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Cardiorespiratory fitness; Preclinical Alzheimer's disease; MRI; White matter hyperintensities; Cognition; Mood ID WHITE-MATTER HYPERINTENSITIES; SURFACE-BASED ANALYSIS; OLDER-ADULTS; PHYSICAL-ACTIVITY; WISCONSIN-REGISTRY; IMPAIRMENT; PREVENTION; PREDICTION; INTEGRITY; DEMENTIA AB Cardiorespiratory fitness (CRF) is an objective measure of habitual physical activity (PA), and has been linked to increased brain structure and cognition. The gold standard method for measuring CRF is graded exercise testing (GXT), but GXT is not feasible in many settings. The objective of this study was to examine whether a non-exercise estimate of CRF is related to gray matter (GM) volumes, white matter hyperintensities (WMH), cognition, objective and subjective memory function, and mood in a middle-aged cohort at risk for Alzheimer's disease (AD). Three hundred and fifteen cognitively healthy adults (mean age =58.58 years) enrolled in the Wisconsin Registry for Alzheimer's Prevention underwent structural MRI scanning, cognitive testing, anthropometric assessment, venipuncture for laboratory tests, and completed a self-reported PA questionnaire. A subset (n = 85) underwent maximal GXT. CRF was estimated using a previously validated equation incorporating sex, age, body-mass index, resting heart rate, and self-reported PA. Results indicated that the CRF estimate was significantly associated with GXT-derived peak oxygen consumption, validating its use as a non-exercise CRF measure in our sample. Support for this finding was seen in significant associations between the CRF estimate and several cardiovascular risk factors. Higher CRF was associated with greater GM volumes in several AD-relevant brain regions including the hippocampus, amygdala, precuneus, supramarginal gyrus, and rostral middle frontal gyrus. Increased CRF was also associated with lower WMH and better cognitive performance in Verbal Learning & Memory, Speed & Flexibility, and Visuospatial Ability. Lastly, CRF was negatively correlated with self- and informant-reported memory complaints, and depressive symptoms. Together, these findings suggest that habitual participation in physical activity may provide protection for brain structure and cognitive function, thereby decreasing future risk for AD. C1 [Boots, Elizabeth A.; Schultz, Stephanie A.; Oh, Jennifer M.; Larson, Jordan; Gallagher, Catherine L.; Carlsson, Cynthia M.; Bendlin, Barbara B.; Asthana, Sanjay; Johnson, Sterling C.; Okonkwo, Ozioma C.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI 53705 USA. [Boots, Elizabeth A.; Schultz, Stephanie A.; Oh, Jennifer M.; Larson, Jordan; Edwards, Dorothy; Dowling, Maritza N.; Gallagher, Catherine L.; Carlsson, Cynthia M.; Rowley, Howard A.; Bendlin, Barbara B.; Asthana, Sanjay; Hermann, Bruce P.; Sager, Mark A.; Johnson, Sterling C.; Okonkwo, Ozioma C.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53792 USA. [Boots, Elizabeth A.; Schultz, Stephanie A.; Oh, Jennifer M.; Larson, Jordan; Edwards, Dorothy; Dowling, Maritza N.; Gallagher, Catherine L.; Carlsson, Cynthia M.; Rowley, Howard A.; Bendlin, Barbara B.; Asthana, Sanjay; Hermann, Bruce P.; Sager, Mark A.; Johnson, Sterling C.; Okonkwo, Ozioma C.] Univ Wisconsin, Alzheimers Dis Res Ctr, Sch Med & Publ Hlth, Madison, WI 53792 USA. [Edwards, Dorothy; Cook, Dane] Univ Wisconsin, Dept Kinesiol, Madison, WI 53706 USA. [Edwards, Dorothy; Koscik, Rebecca L.; Bendlin, Barbara B.; LaRue, Asenath; Asthana, Sanjay; Hermann, Bruce P.; Sager, Mark A.; Johnson, Sterling C.; Okonkwo, Ozioma C.] Univ Wisconsin, Wisconsin Alzheimers Inst, Sch Med & Publ Hlth, Madison, WI 53705 USA. [Dowling, Maritza N.] Univ Wisconsin, Dept Biostat & Med Informat, Sch Med & Publ Hlth, Madison, WI 53792 USA. [Gallagher, Catherine L.; Hermann, Bruce P.] Univ Wisconsin, Dept Neurol, Sch Med & Publ Hlth, Madison, WI 53705 USA. [Rowley, Howard A.] Univ Wisconsin, Dept Radiol, Sch Med & Publ Hlth, Madison, WI 53792 USA. RP Okonkwo, OC (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53792 USA. EM ozioma@medicine.wisc.edu OI Bendlin, Barbara/0000-0002-0580-9875; Schultz, Stephanie/0000-0001-8460-4415 FU National Institute on Aging [K23 AG045957, R01 AG027161, R01 AG021155, P50 AG033514, P50 AG033514-S1]; Veterans Administration Merit Review Grant [I01CX000165]; Clinical and Translational Science Award [UL1RR025011]; Wisconsin Alumni Research Foundation; Helen Bader Foundation; Northwestern Mutual Foundation; Extendicare Foundation; Veterans Administration FX This work was supported by National Institute on Aging grants K23 AG045957 (OCO), R01 AG027161 (MAS), R01 AG021155 (SCJ), P50 AG033514 (SA), and P50 AG033514-S1 (OCO); by a Veterans Administration Merit Review Grant I01CX000165 (SCJ); and by a Clinical and Translational Science Award (UL1RR025011) to the University of Wisconsin, Madison. Portions of this research were supported by the Wisconsin Alumni Research Foundation, the Helen Bader Foundation, Northwestern Mutual Foundation, Extendicare Foundation, and from the Veterans Administration including facilities and resources at the Geriatric Research Education and Clinical Center of the William S. Middleton Memorial Veterans Hospital, Madison, WI. NR 53 TC 9 Z9 9 U1 0 U2 24 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 EI 1931-7565 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD SEP PY 2015 VL 9 IS 3 BP 639 EP 649 DI 10.1007/s11682-014-9325-9 PG 11 WC Neuroimaging SC Neurosciences & Neurology GA CR8LQ UT WOS:000361604300022 PM 25319359 ER PT J AU Zhao, XS Ponomaryov, T Ornell, KJ Zhou, PC Dabral, SK Pak, E Li, W Atwood, SX Whitson, RJ Chang, ALS Li, J Oro, AE Chan, JA Kelleher, JF Segal, RA AF Zhao, Xuesong Ponomaryov, Tatyana Ornell, Kimberly J. Zhou, Pengcheng Dabral, Sukriti K. Pak, Ekaterina Li, Wei Atwood, Scott X. Whitson, Ramon J. Chang, Anne Lynn S. Li, Jiang Oro, Anthony E. Chan, Jennifer A. Kelleher, Joseph F. Segal, Rosalind A. TI RAS/MAPK Activation Drives Resistance to Smo Inhibition, Metastasis, and Tumor Evolution in Shh Pathway-Dependent Tumors SO CANCER RESEARCH LA English DT Article ID BASAL-CELL CARCINOMA; CANCER STEM-CELLS; HEDGEHOG PATHWAY; ACQUIRED-RESISTANCE; SONIC HEDGEHOG; MEDULLOBLASTOMA DEVELOPMENT; SMOOTHENED ANTAGONISTS; MOUSE MEDULLOBLASTOMA; VISMODEGIB; GROWTH AB Aberrant Shh signaling promotes tumor growth in diverse cancers. The importance of Shh signaling is particularly evident in medulloblastoma and basal cell carcinoma (BCC), where inhibitors targeting the Shh pathway component Smoothened (Smo) show great therapeutic promise. However, the emergence of drug resistance limits long-term efficacy, and the mechanisms of resistance remain poorly understood. Using new medulloblastoma models, we identify two distinct paradigms of resistance to Smo inhibition. Sufu mutations lead to maintenance of the Shh pathway in the presence of Smo inhibitors. Alternatively activation of the RAS-MAPK pathway circumvents Shh pathway dependency, drives tumor growth, and enhances metastatic behavior. Strikingly, in BCC patients treated with Smo inhibitor, squamous cell cancers with RAS/MAPK activation emerged from the antecedent BCC tumors. Together, these findings reveal a critical role of the RAS-MAPK pathway in drug resistance and tumor evolution of Shh pathway-dependent tumors. (C) 2015 AACR. C1 [Zhao, Xuesong; Ponomaryov, Tatyana; Ornell, Kimberly J.; Zhou, Pengcheng; Dabral, Sukriti K.; Pak, Ekaterina; Segal, Rosalind A.] Dana Farber Canc Inst, Canc Biol & Pediat Oncol, Boston, MA 02115 USA. [Zhao, Xuesong; Ponomaryov, Tatyana; Ornell, Kimberly J.; Zhou, Pengcheng; Dabral, Sukriti K.; Pak, Ekaterina; Segal, Rosalind A.] Harvard Univ, Sch Med, Neurobiol, Boston, MA USA. [Ponomaryov, Tatyana] Univ Birmingham, Ctr Cardiovasc Sci, Coll Med & Dent Sci, Birmingham, W Midlands, England. [Li, Wei] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Biostat & Computat Biol, Boston, MA 02115 USA. [Atwood, Scott X.; Whitson, Ramon J.; Chang, Anne Lynn S.; Li, Jiang; Oro, Anthony E.] Stanford Univ, Sch Med, Program Epithelial Biol, Stanford, CA 94305 USA. [Chan, Jennifer A.] Univ Calgary, Pathol & Lab Med, Calgary, AB, Canada. [Kelleher, Joseph F.] Novartis Inst Biomed Res, Cambridge, MA USA. RP Segal, RA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM rosalind_segal@dfci.harvard.edu OI Atwood, Scott/0000-0001-7407-9792 FU NIH [CA142536, ARO4786, 5ARO54780, HG4069]; Novartis Pharmaceuticals; Emerald Foundation; Alex's Lemonade Stand Foundation; Autism Speaks Foundation; American Brain Tumor Association FX This study was supported by grants from the NIH (CA142536 to RAS, ARO4786, and 5ARO54780 to A.E. Oro; HG4069 supports W. Li), Novartis Pharmaceuticals, the Emerald Foundation, Alex's Lemonade Stand Foundation, Autism Speaks Foundation, and the American Brain Tumor Association. NR 56 TC 14 Z9 15 U1 0 U2 5 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 SEP 1 PY 2015 VL 75 IS 17 BP 3623 EP 3635 DI 10.1158/0008-5472.CAN-14-2999-T PG 13 WC Oncology SC Oncology GA CS2QV UT WOS:000361917100018 PM 26130651 ER PT J AU Wasfy, JH Singal, G O'Brien, C Blumenthal, DM Kennedy, KF Strom, JB Spertus, JA Mauri, L Normand, SLT Yeh, RW AF Wasfy, Jason H. Singal, Gaurav O'Brien, Cashel Blumenthal, Daniel M. Kennedy, Kevin F. Strom, Jordan B. Spertus, John A. Mauri, Laura Normand, Sharon-Lise T. Yeh, Robert W. TI Enhancing the Prediction of 30-Day Readmission After Percutaneous Coronary Intervention Using Data Extracted by Querying of the Electronic Health Record SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE bioinformatics; health policy and outcomes research; percutaneous coronary intervention; performance measures; readmission ID POSTOPERATIVE COMPLICATIONS; ADVERSE EVENTS; LEFT MAIN; RISK; LANGUAGE; SURGERY; FRAILTY; IMPACT; BIASES; MODEL AB Background Early readmission after percutaneous coronary intervention is an important quality metric, but prediction models from registry data have only moderate discrimination. We aimed to improve ability to predict 30-day readmission after percutaneous coronary intervention from a previously validated registry-based model. Methods and Results We matched readmitted to non-readmitted patients in a 1:2 ratio by risk of readmission, and extracted unstructured and unconventional structured data from the electronic medical record, including need for medical interpretation, albumin level, medical nonadherence, previous number of emergency department visits, atrial fibrillation/flutter, syncope/presyncope, end-stage liver disease, malignancy, and anxiety. We assessed differences in rates of these conditions between cases/controls, and estimated their independent association with 30-day readmission using logistic regression conditional on matched groups. Among 9288 percutaneous coronary interventions, we matched 888 readmitted with 1776 non-readmitted patients. In univariate analysis, cases and controls were significantly different with respect to interpreter (7.9% for cases and 5.3% for controls; P=0.009), emergency department visits (1.12 for cases and 0.77 for controls; P<0.001), homelessness (3.2% for cases and 1.6% for controls; P=0.007), anticoagulation (33.9% for cases and 22.1% for controls; P<0.001), atrial fibrillation/flutter (32.7% for cases and 28.9% for controls; P=0.045), presyncope/syncope (27.8% for cases and 21.3% for controls; P<0.001), and anxiety (69.4% for cases and 62.4% for controls; P<0.001). Anticoagulation, emergency department visits, and anxiety were independently associated with readmission. Conclusions Patient characteristics derived from review of the electronic health record can be used to refine risk prediction for hospital readmission after percutaneous coronary intervention. C1 [Wasfy, Jason H.; O'Brien, Cashel; Blumenthal, Daniel M.; Yeh, Robert W.] Harvard Univ, Sch Med, Dept Med, Cardiol Div,Massachusetts Gen Hosp, Boston, MA USA. [Mauri, Laura] Harvard Univ, Brigham & Womens Hosp, Sch Med, Cardiovasc Div,Dept Med, Boston, MA 02115 USA. [Singal, Gaurav] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. [Strom, Jordan B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Cardiovasc Div,Dept Med, Boston, MA 02215 USA. [Kennedy, Kevin F.; Spertus, John A.] St Lukes Mid Amer Heart Inst UMKC, Kansas City, MO USA. [Normand, Sharon-Lise T.] Harvard Univ, Dept Biostat, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. RP Yeh, RW (reprint author), Massachusetts Gen Hosp, Div Cardiol, GRB 8-843,55 Fruit St, Boston, MA 02114 USA. EM ryeh@partners.org FU Hassenfeld Scholars Program (Boston, Massachusetts); American Heart Association (Dallas, TX) [12CRP9010016] FX This work was supported, in part, by the Hassenfeld Scholars Program (Boston, Massachusetts) and a grant (12CRP9010016) from the American Heart Association (Dallas, TX). NR 37 TC 5 Z9 5 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD SEP PY 2015 VL 8 IS 5 BP 477 EP 485 DI 10.1161/CIRCOUTCOMES.115.001855 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR3AX UT WOS:000361203600006 PM 26286871 ER PT J AU Lee, GC Sylla, P AF Lee, Grace Clara Sylla, Patricia TI Shifting Paradigms in Minimally Invasive Surgery: Applications of Transanal Natural Orifice Transluminal Endoscopic Surgery in Colorectal Surgery SO CLINICS IN COLON AND RECTAL SURGERY LA English DT Article DE transanal; NOTES; TME; mesorectal excision; proctectomy ID TOTAL MESORECTAL EXCISION; LOW ANTERIOR RESECTION; LOW RECTAL-CANCER; SHORT-TERM OUTCOMES; PROSPECTIVE RANDOMIZED-TRIAL; QUALITY-OF-LIFE; LOCAL EXCISION; PORCINE MODEL; SINGLE-PORT; INTERSPHINCTERIC RESECTION AB Since the advent of laparoscopy, minimally invasive techniques such as single port laparoscopy, robotics, endoscopically assisted laparoscopy, and transanal endoscopic surgery continue to revolutionize the field of colorectal surgery. Transanal natural orifice transluminal endoscopic surgery (NOTES) represents a further paradigm shift by combining the advantages of these earlier techniques to reduce the size and number of abdominal incisions and potentially optimize rectal dissection, especially with respect to performance of an oncologically adequate total mesorectal excision (TME) for rectal cancer. Since the first experimental report of transanal rectosigmoid resection in 2007, the potential impact of transanal NOTES in colorectal surgery has been extensively investigated in experimental models and recently transitioned to clinical application. There have been 14 clinical trials of transanal TME (taTME) for rectal cancer that have demonstrated the feasibility and preliminary oncologic safety of this approach in carefully selected patients, with results comparable to outcomes after laparoscopic and open TME, including cumulative intraoperative and postoperative complication rates of 5.5 and 35.5%, respectively, 97.3% rate of complete or near-complete specimens, and 93.6% rate of negative margins. Transanal NOTES has also been safely applied to proctectomy and colectomy for benign indications. The consensus among published series suggests that taTME is most safely performed with transabdominal assistance by surgeons experienced with laparoscopic TME, transanal endoscopic surgery, and sphincter-preserving techniques including intersphincteric resection. Future applications of transanal NOTES may include evolution to a pure endoscopic transanal approach for TME, colectomy, and sentinel lymph node biopsy for rectal cancer, with a potential role for robotic assistance. C1 [Lee, Grace Clara; Sylla, Patricia] Massachusetts Gen Hosp, Dept Surg, Div Gastrointestinal Surg, Boston, MA 02114 USA. RP Sylla, P (reprint author), Mt Sinai Hosp, Div Colon & Rectal Surg, Dept Surg, 5 East 98th St,Box 1259, New York, NY 10029 USA. EM patricia.sylla@mountsinai.org NR 143 TC 2 Z9 2 U1 0 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1531-0043 EI 1530-9681 J9 CLIN COLON RECT SURG JI Clin. Colon Rectal Surg. PD SEP PY 2015 VL 28 IS 3 BP 181 EP 193 DI 10.1055/s-0035-1555009 PG 13 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA CR8ZR UT WOS:000361643500011 PM 26491411 ER PT J AU Hall, JE AF Hall, Janet E. TI Endocrinology of the Menopause SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article DE Ovary; Hypothalamus; Pituitary; Menopause; Estradiol; Follicle-stimulating hormone ID GONADOTROPIN-RELEASING-HORMONE; ANTI-MULLERIAN HORMONE; FOLLICLE-STIMULATING-HORMONE; STRENGTH-DURATION CHARACTERISTICS; REPRODUCTIVE-AGE WOMEN; POSTMENOPAUSAL WOMEN; INHIBIN-B; NATURAL MENOPAUSE; OVARIAN-FUNCTION; LUTEINIZING-HORMONE AB In women, age-related changes in ovarian function begin in the mid-30s with decreased fertility and compensatory hormonal changes in the hypothalamus-pituitary-gonadal axis that maintain follicle development and estrogen secretion in the face of a waning pool of ovarian follicles. The menopause transition is characterized by marked variability in follicle development, ovulation, bleeding patterns, and symptoms of hyper- and hypoestrogenism. The menopause, which is clinically defined by the final menstrual period, is followed by the consistent absence of ovarian secretion of estradiol. C1 [Hall, Janet E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Reprod Endocrine Unit, Boston, MA 02460 USA. [Hall, Janet E.] NIEHS, Res Triangle Pk, NC 27709 USA. RP Hall, JE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Reprod Endocrine Unit, 55 Fruit St, Boston, MA 02460 USA. EM hall.janet@mgh.harvard.edu OI Hall, Janet/0000-0003-4644-3061 NR 78 TC 2 Z9 2 U1 4 U2 12 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8529 EI 1558-4410 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD SEP PY 2015 VL 44 IS 3 BP 485 EP + DI 10.1016/j.ecl.2015.05.010 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CS0UF UT WOS:000361777000004 PM 26316238 ER PT J AU Rajaiya, J Zhou, XH Barequet, I Gilmore, MS Chodosh, J AF Rajaiya, Jaya Zhou, Xiaohong Barequet, Irina Gilmore, Michael S. Chodosh, James TI Novel model of innate immunity in corneal infection SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE Keratitis; Adenovirus; In vitro model ID ADENOVIRUS TYPE-19 INFECTION; INTERLEUKIN-8 IL-8; IN-VIVO; KERATITIS; MOUSE; CELL; ACTIVATION; KERATOCYTE; CANCER; TISSUE AB The cornea functions as the major refractive interface for vision and protects the internal eye from insult. Current understanding of innate immune responses to corneal infection derives from a synthesis of in vitro and in vivo analyses. However, monolayer cell cultures and mouse models do not accurately duplicate all aspects of innate immunity in human patients. Here, we describe a three-dimensional culture system that incorporates human cells and extracellular matrix to more completely simulate the human cornea for studies of infection. Human corneal stromal fibroblasts were mixed with type I collagen in 3-mu m pore size transwell inserts, and overlayed with Matrigel to simulate a human corneal stroma and epithelial basement membrane. These were then infected with a cornea-tropic adenovirus, and exposed on their inferior side to leukocytes derived from human peripheral blood. Subsequent analyses were performed with histology, confocal microscopy, ELISA, and fluorescence-activated cell sorting (FACS). CXCL8, a neutrophil chemokine shown previously as the first cytokine induced in infection of human corneal cells, increased upon adenovirus infection of facsimiles in a dose-responsive fashion. Myeloperoxidase-positive cells infiltrated infected corneal facsimiles in a sub-Matrigel location, possibly due to CXCL8 colocalization with heparan sulfate, a Matrigel constituent. Cellular infiltration was significantly inhibited by treatment with chemical inhibitors of p38 MAPK and Src kinase, both constituents of a signaling cascade previously suggested to regulate inflammation after adenovirus infection. FACS analysis determined that both virus and corneal fibroblasts were necessary for the induction of leukocyte migration into the facsimiles. The corneal facsimile, literally a cornea in a test tube, permits mechanistic studies on human tissue in a highly tractable system. C1 [Rajaiya, Jaya; Zhou, Xiaohong; Barequet, Irina; Gilmore, Michael S.; Chodosh, James] Harvard Univ, Dept Ophthalmol, Howe Lab, Massachusetts Eye & Ear Infirm,Med Sch, Boston, MA 02114 USA. [Chodosh, James] Massachusetts Eye & Ear Infirm, Howe Lab, Boston, MA 02114 USA. RP Chodosh, J (reprint author), Massachusetts Eye & Ear Infirm, Howe Lab, 243 Charles St, Boston, MA 02114 USA. EM james_chodosh@meei.harvard.edu FU NEI NIH HHS [R01 EY013124, R01 EY021558, EY01324, P30 EY014104] NR 46 TC 1 Z9 1 U1 2 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-2690 EI 1543-706X J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD SEP PY 2015 VL 51 IS 8 BP 827 EP 834 DI 10.1007/s11626-015-9910-2 PG 8 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA CR7VL UT WOS:000361559800008 PM 25977076 ER PT J AU MacDonald, SC Bateman, BT McElrath, TF Hernandez-Diaz, S AF MacDonald, Sarah C. Bateman, Brian T. McElrath, Thomas F. Hernandez-Diaz, Sonia TI Mortality and Morbidity During Delivery Hospitalization Among Pregnant Women With Epilepsy in the United States SO JAMA NEUROLOGY LA English DT Article ID TECHNOLOGY-ASSESSMENT SUBCOMMITTEE; QUALITY STANDARDS SUBCOMMITTEE; UPDATE MANAGEMENT ISSUES; ANTIEPILEPTIC DRUGS; MATERNAL MORBIDITY; AMERICAN ACADEMY; BIRTH-WEIGHT; OUTCOMES; COMPLICATIONS; THERAPEUTICS AB IMPORTANCE Between 0.3% and 0.5% of all pregnancies occur among women with epilepsy. Evidence suggests an increase in perinatal morbidity and mortality among women with epilepsy. However, these risks have not been quantified in large population-based samples. OBJECTIVE To report on the risk for death and adverse outcomes at the time of delivery for women with epilepsy in the United States. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of pregnant women identified through delivery hospitalization records from the 2007-2011 Nationwide Inpatient Sample. From this representative sample of 20% of all US hospitals, we obtained a weighted sample of delivery hospitalizations from 69 385 women with epilepsy and 20 449 532 women without epilepsy. MAIN OUTCOMES AND MEASURES Obstetrical outcomes including maternal death, cesarean delivery, length of stay, preeclampsia, preterm labor, and stillbirth. RESULTS Women with epilepsy had a risk of death during delivery hospitalization of 80 deaths per 100 000 pregnancies, significantly higher than the 6 deaths per 100 000 pregnancies found among women without epilepsy (adjusted odds ratio [OR], 11.46 [95% CI, 8.64-15.19]). Women with epilepsy were also at a heightened risk for other adverse outcomes, including preeclampsia (adjusted OR, 1.59 [95% CI, 1.54-1.63]), preterm labor (adjusted OR, 1.54 [95% CI, 1.50-1.57]), and stillbirth (adjusted OR, 1.27 [95% CI, 1.17-1.38]), and had increased health care utilization, including an increased risk of cesarean delivery (adjusted OR, 1.40 [95% CI, 1.38-1.42]) and prolonged length of hospital stay (>6 days) among both women with cesarean deliveries (adjusted OR, 2.13 [95% CI, 2.03-2.23]) and women with vaginal deliveries (adjusted OR, 2.60 [95% CI, 2.41-2.80]). CONCLUSIONS AND RELEVANCE Findings suggest that women with epilepsy are at considerably heightened risk for many adverse outcomes during their delivery hospitalization, including a more than 10-fold increased risk of death, and that increased clinical attention is imperative for these pregnancies. C1 [MacDonald, Sarah C.; Hernandez-Diaz, Sonia] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Bateman, Brian T.] Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Dept Med, Boston, MA 02115 USA. [Bateman, Brian T.; McElrath, Thomas F.] Harvard Univ, Sch Med, Boston, MA USA. [Bateman, Brian T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. [McElrath, Thomas F.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02115 USA. RP MacDonald, SC (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave,Kresge Bldg,Room 816, Boston, MA 02115 USA. EM smacdonald@mail.harvard.edu FU National Institute for Mental Health [R01MH100216]; Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health [K08HD075831] FX This work was supported by the National Institute for Mental Health (grant R01MH100216 to Dr Hernandez-Diaz) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (award K08HD075831 to Dr Bateman). NR 38 TC 14 Z9 14 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD SEP PY 2015 VL 72 IS 9 BP 981 EP 988 DI 10.1001/jamaneurol.2015.1017 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA CS0MU UT WOS:000361755400006 PM 26147878 ER PT J AU Willette, AA Bendlin, BB Starks, EJ Birdsill, AC Johnson, SC Christian, BT Okonkwo, OC La Rue, A Hermann, BP Koscik, RL Jonaitis, EM Sager, MA Asthana, S AF Willette, Auriel A. Bendlin, Barbara B. Starks, Erika J. Birdsill, Alex C. Johnson, Sterling C. Christian, Bradley T. Okonkwo, Ozioma C. La Rue, Asenath Hermann, Bruce P. Koscik, Rebecca L. Jonaitis, Erin M. Sager, Mark A. Asthana, Sanjay TI Association of Insulin Resistance With Cerebral Glucose Uptake in Late Middle-Aged Adults at Risk for Alzheimer Disease SO JAMA NEUROLOGY LA English DT Article ID MILD COGNITIVE IMPAIRMENT; FDG-PET; METABOLIC SYNDROME; DIFFERENTIAL-DIAGNOSIS; IMPROVES COGNITION; WISCONSIN-REGISTRY; NORMAL INDIVIDUALS; APOLIPOPROTEIN-E; RAT-BRAIN; LATE-LIFE AB IMPORTANCE Converging evidence suggests that Alzheimer disease (AD) involves insulin signaling impairment. Patients with AD and individuals at risk for AD show reduced glucose metabolism, as indexed by fludeoxyglucose F 18-labeled positron emission tomography (FDG-PET). OBJECTIVES To determine whether insulin resistance predicts AD-like global and regional glucose metabolism deficits in late middle-aged participants at risk for AD and to examine whether insulin resistance-predicted variation in regional glucose metabolism is associated with worse cognitive performance. DESIGN, SETTING, AND PARTICIPANTS This population-based, cross-sectional study included 150 cognitively normal, late middle-aged (mean [SD] age, 60.7 [5.8] years) adults from the Wisconsin Registry for Alzheimer's Prevention (WRAP) study, a general community sample enriched for AD parental history. Participants underwent cognitive testing, fasting blood draw, and FDG-PET at baseline. We used the homeostatic model assessment of peripheral insulin resistance (HOMA-IR). Regression analysis tested the statistical effect of HOMA-IR on global glucose metabolism. We used a voxelwise analysis to determine whether HOMA-IR predicted regional glucose metabolism. Finally, predicted variation in regional glucose metabolism was regressed against cognitive factors. Covariates included age, sex, body mass index, apolipoprotein E epsilon 4 genotype, AD parental history status, and a reference region used to normalize regional uptake. MAIN OUTCOMES AND MEASURES Regional glucose uptake determined using FDG-PET and neuropsychological factors. RESULTS Higher HOMA-IR was associated with lower global glucose metabolism (beta = -0.29; P < .01) and lower regional glucose metabolism across large portions of the frontal, lateral parietal, lateral temporal, and medial temporal lobes (P < .05, familywise error corrected). The association was especially robust in the left medial temporal lobe (R-2 = 0.178). Lower glucose metabolism in the left medial temporal lobe predicted by HOMA-IR was significantly related to worse performance on the immediate memory (beta = 0.317; t(148) = 4.08; P < .001) and delayed memory (beta = 0.305; t(148) = 3.895; P < .001) factor scores. CONCLUSIONS AND RELEVANCE Our results show that insulin resistance, a prevalent and increasingly common condition in developed countries, is associated with significantly lower regional cerebral glucose metabolism, which in turn may predict worse memory performance. Midlife may be a critical period for initiating treatments to lower peripheral insulin resistance to maintain neural metabolism and cognitive function. C1 [Willette, Auriel A.] Iowa State Univ, Dept Food Sci & Human Nutr, Ames, IA USA. [Willette, Auriel A.] Iowa State Univ, Neurosci Interdept Program, Ames, IA USA. [Bendlin, Barbara B.; Starks, Erika J.; Birdsill, Alex C.; Johnson, Sterling C.; Okonkwo, Ozioma C.; Asthana, Sanjay] Univ Wisconsin, Sch Med & Publ Hlth, Ctr Clin Sci, Wisconsin Alzheimers Dis Res Ctr, Madison, WI 53792 USA. [Bendlin, Barbara B.; Johnson, Sterling C.; Okonkwo, Ozioma C.; La Rue, Asenath; Hermann, Bruce P.; Koscik, Rebecca L.; Jonaitis, Erin M.; Sager, Mark A.] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Inst, Madison, WI 53792 USA. [Johnson, Sterling C.; Asthana, Sanjay] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Christian, Bradley T.] Univ Wisconsin, Dept Med Phys, Sch Med & Publ Hlth, Madison, WI 53706 USA. RP Bendlin, BB (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Ctr Clin Sci, Wisconsin Alzheimers Dis Res Ctr, Sect J5-1M,600 Highland Ave, Madison, WI 53792 USA. EM bbb@medicine.wisc.edu FU National Institute on Aging [R01 AG037639, R01 AG027161, P50 AG033514, R01 AG021155]; Alzheimer's Disease Research Center from University of Wisconsin Institute for Clinical and Translational Research [5977]; National Center for Research Resources/National Institutes of Health [1UL1RR025011]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [P30 HD03352]; Department of Food Science and Human Nutrition, Iowa State University FX This study was supported by grants R01 AG037639 (Dr Bendlin), R01 AG027161 (Dr Johnson), P50 AG033514 (Dr Asthana), and R01 AG021155 (Dr Johnson), National Institute on Aging; by Alzheimer's Disease Research Center subproject 5977 (Dr Bendlin) from the University of Wisconsin Institute for Clinical and Translational Research, funded through Clinical and Translational Science Award 1UL1RR025011 from the National Center for Research Resources/National Institutes of Health; by grant P30 HD03352 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development; by funding from the Department of Food Science and Human Nutrition, Iowa State University; and by the facilities and resources at the Geriatric Research, Education, and Clinical Center of the William S. Middleton Memorial Veterans Hospital. NR 70 TC 31 Z9 31 U1 8 U2 18 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 SEP PY 2015 VL 72 IS 9 BP 1013 EP 1020 DI 10.1001/jamaneurol.2015.0613 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA CS0MU UT WOS:000361755400010 PM 26214150 ER PT J AU Gregg, NM Kim, AE Gurol, ME Lopez, OL Aizenstein, HJ Price, JC Mathis, CA James, JA Snitz, BE Cohen, AD Kamboh, MI Minhas, D Weissfeld, LA Tamburo, EL Klunk, WE AF Gregg, Nicholas M. Kim, Albert E. Gurol, M. Edip Lopez, Oscar L. Aizenstein, Howard J. Price, Julie C. Mathis, Chester A. James, Jeffrey A. Snitz, Beth E. Cohen, Ann D. Kamboh, M. Ilyas Minhas, Davneet Weissfeld, Lisa A. Tamburo, Erica L. Klunk, William E. TI Incidental Cerebral Microbleeds and Cerebral Blood Flow in Elderly Individuals SO JAMA NEUROLOGY LA English DT Article ID MILD COGNITIVE IMPAIRMENT; BETA-AMYLOID DEPOSITION; ALZHEIMER-DISEASE; RISK-FACTORS; MR-IMAGES; ANGIOPATHY; DEMENTIA; BRAIN; PREVALENCE; HEMORRHAGE AB IMPORTANCE Cerebral microbleeds (CMBs) are collections of blood breakdown products that are a common incidental finding in magnetic resonance imaging of elderly individuals. Cerebral microbleeds are associated with cognitive deficits, but the mechanism is unclear. Studies show that individuals with CMBs related to symptomatic cerebral amyloid angiopathy have abnormal vascular reactivity and cerebral blood flow (CBF), but, to our knowledge, abnormalities in cerebral blood flow have not been reported for healthy individuals with incidental CMBs. OBJECTIVE To evaluate the association of incidental CMBs with resting-state CBF, cerebral metabolism, cerebrovascular disease, beta-amyloid (A beta), and cognition. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional study of 55 cognitively normal individuals with a mean (SD) age of 86.8 (2.7) years was conducted from May 1, 2010, to May 1, 2013, in an academic medical center in Pittsburgh; data analysis was performed between June 10, 2013, and April 9, 2015. INTERVENTIONS 3-Tesla magnetic resonance imaging was performed with susceptibility-weighted imaging or gradient-recalled echo to assess CMBs, arterial spin labeling for CBF, and T1- and T2-weighted imaging for atrophy, white matter hyperintensities, and infarcts. Positron emission tomography was conducted with fluorodeoxyglucose to measure cerebral metabolism and Pittsburgh compound B for fibrillar A beta. Neuropsychological evaluation, including the Clinical Dementia Rating scale, was performed. MAIN OUTCOMES AND MEASURES Magnetic resonance images were rated for the presence and location of CMBs. Lobar CMBs were subclassified as cortical or subcortical. Measurements of CBF, metabolism, and A beta were compared with the presence and number of CMBs with voxelwise and region-of-interest analyses. RESULTS The presence of cortical CMBs was associated with significantly reduced CBF in multiple regions on voxelwise and region-of-interest analyses (percentage difference in global CBF, -25.3%; P = .0003), with the largest reductions in the parietal cortex (-37.6%; P < .0001) and precuneus (-31.8%; P = .0006). Participants with any CMBs showed a nonsignificant trend toward reduced CBF. Participants with cortical CMBs had a significant association with greater prevalence of infarcts (24% vs 6%; P = .047) and demonstrated a trend to greater prevalence of deficits demonstrated on the Clinical Dementia Rating scale (45% vs 19%; P = .12). There was no difference in cortical amyloid (measured by Pittsburgh compound B positron emission tomography) between participants with and without CMBs (P = .60). CONCLUSIONS AND RELEVANCE In cognitively normal elderly individuals, incidental CMBs in cortical locations are associated with widespread reductions in resting-state CBF. Chronic hypoperfusion may put these people at risk for neuronal injury and neurodegeneration. Our results suggest that resting-state CBF is a marker of CMB-related small-vessel disease. C1 [Gregg, Nicholas M.; Kim, Albert E.; Aizenstein, Howard J.; Cohen, Ann D.; Tamburo, Erica L.; Klunk, William E.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. [Gurol, M. Edip] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Gurol, M. Edip] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Lopez, Oscar L.; Snitz, Beth E.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Price, Julie C.; Mathis, Chester A.; James, Jeffrey A.; Minhas, Davneet] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15260 USA. [Kamboh, M. Ilyas] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. [Weissfeld, Lisa A.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. RP Klunk, WE (reprint author), Univ Pittsburgh, Dept Psychiat, 3811 OHara St,Room 1422, Pittsburgh, PA 15213 USA. EM klunkwe@upmc.edu RI Gurol, Edip/J-2279-2014; OI Gurol, Edip/0000-0002-2169-4457; Kamboh, M. Ilyas/0000-0002-3453-1438 FU National Institutes of Health [P50 AG005133, R37 AG025516, P01 AG025204, AG041718, AG030653, T32NS048005] FX This study was supported in part by National Institutes of Health grants P50 AG005133 (Drs Lopez and Klunk), R37 AG025516 (Dr Klunk), P01 AG025204 (Dr Klunk), AG041718 (Dr Kamboh), AG030653 (Dr Kamboh), and T32NS048005 (Dr Gurol). NR 30 TC 14 Z9 14 U1 0 U2 2 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 SEP PY 2015 VL 72 IS 9 BP 1021 EP 1028 DI 10.1001/jamaneurol.2015.1359 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA CS0MU UT WOS:000361755400011 PM 26167811 ER PT J AU McKee, KE Etherton, MR Lovitch, SB Gupta, AS Micalizzi, DS Tierney, T Wadleigh, M Vaitkevicus, H AF McKee, Kathleen E. Etherton, Mark R. Lovitch, Scott B. Gupta, Anoopum S. Micalizzi, Douglas S. Tierney, Travis Wadleigh, Martha Vaitkevicus, Henrikas TI A Man in His 40s With Headache, Lethargy, and Altered Mental Status SO JAMA NEUROLOGY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CENTRAL-NERVOUS-SYSTEM; OF-THE-LITERATURE; GRANULOCYTIC SARCOMA; TUMORS; MIMICKING; CHLOROMA; CANCER; MASS AB A man in his 40s presented with 1 month of worsening confusion, fatigue, and headache. Results from laboratory analyses were notable for a complete white blood cell count of 17 000/mu L (31% blast cells), a platelet count of 76 000/mu L, and a hemoglobin level of 16.6 g/dL. Imaging studies revealed a large mixed-attenuation subdural collection in the right frontal region with prominent mass effect. The patient underwent an emergency neurosurgical procedure. The differential diagnosis, pathologic findings, and diagnosis are discussed. C1 [McKee, Kathleen E.; Etherton, Mark R.; Gupta, Anoopum S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [McKee, Kathleen E.; Etherton, Mark R.; Gupta, Anoopum S.; Vaitkevicus, Henrikas] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [McKee, Kathleen E.; Etherton, Mark R.; Gupta, Anoopum S.; Vaitkevicus, Henrikas] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Lovitch, Scott B.; Wadleigh, Martha] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Micalizzi, Douglas S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Tierney, Travis] Harvard Univ, Sch Med, Dept Neurosurg, Boston, MA USA. [Tierney, Travis] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. RP McKee, KE (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,Wang Ambulatory Care Ctr Room 720, Boston, MA 02114 USA. EM kmckee1@partners.org OI Lovitch, Scott/0000-0001-9013-0105 NR 19 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 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD SEP PY 2015 VL 72 IS 9 BP 1061 EP 1065 DI 10.1001/jamaneurol.2015.1375 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA CS0MU UT WOS:000361755400015 PM 26213984 ER PT J AU Offodile, AC Pathak, A Wenger, J Orgill, DP Guo, LF AF Offodile, Anaeze C., II Pathak, Abraham Wenger, Julia Orgill, Dennis P. Guo, Lifei TI Prevalence and Patient-Level Risk Factors for 30-Day Readmissions Following Free Tissue Transfer for Head and Neck Cancer SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID QUALITY-OF-LIFE; MICROVASCULAR RECONSTRUCTION; UNPLANNED READMISSION; HOSPITAL READMISSION; OROPHARYNGEAL CANCER; ONCOLOGIC SURGERY; IMPROVEMENT; COMPLICATIONS; POPULATION; DISCHARGE AB IMPORTANCE Hospital readmissions are a marker of surgical care delivery and quality that are progressively more scrutinized. OBJECTIVE To provide a comprehensive analysis of 30-day readmissions for patients with head and neck cancer who underwent free flap reconstruction to highlight the rate, causes, and associated patient risk factors. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study at a single tertiary care academic institution. The study consisted of 249 patients who underwent microvascular reconstruction of a presumed head and neck oncologic defect from January 1, 2000, through June 30, 2014. Follow-up continued through July 30, 2014. INTERVENTIONS Microvascular reconstruction of an oncologic head and neck defect. MAIN OUTCOMES AND MEASURES Incidence of 30-day all-cause readmissions, patient risk factors, and readmission indications. Regression analyses were conducted to discern patient-level risk factors related to 30-day readmissions. RESULTS Among the 249 patients, the 30-day all-cause readmission rate was 14.5%, while the unplanned readmission rate was 11.6%. The most common reason for readmission was neck wound complications. Predictors of readmission following multivariable analysis were T4 pathologic stage (odds ratio [OR], 11.68; 95% CI, 1.37-99.81; P =.02) and having a tumor located in the oropharynx (OR, 4.64; 95% CI, 1.89-11.38; P =.001), hypopharynx (OR, 8.30; 95% CI, 1.52-45.24; P =.01), or larynx (OR, 10.97; 95% CI, 2.27-52.98; P =.003). Patients who were readmitted were more likely to experience neck wound complications (OR, 5.07; 95% CI, 1.31-19.57; P =.02) and undergo reoperation (OR, 47.20; 95% CI, 8.33-267.33; P <.001). CONCLUSIONS AND RELEVANCE In this study, advanced pathologic tumor staging and tumor location were associated with 30-day readmissions in patients with head and neck cancer who receive free flaps. Our results provide a benchmark for risk stratification that can be used in system-based practice improvements, health care cost savings, and postoperative patient counseling. C1 [Offodile, Anaeze C., II; Guo, Lifei] Lahey Hosp & Med Ctr, Dept Plast Surg, Burlington, MA 01805 USA. [Pathak, Abraham; Orgill, Dennis P.] Brigham & Womens Hosp, Dept Surg, Div Plast Surg, Boston, MA 02115 USA. [Wenger, Julia] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. RP Guo, LF (reprint author), Lahey Hosp & Med Ctr, Dept Plast Surg, 41 Mall Rd, Burlington, MA 01805 USA. EM lifei.guo@lahey.org NR 24 TC 2 Z9 2 U1 3 U2 5 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 SEP PY 2015 VL 141 IS 9 BP 783 EP 789 DI 10.1001/jamaoto.2015.1323 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CS0NQ UT WOS:000361758200001 PM 26204558 ER PT J AU Shay, SG Chang, E Lewis, MS Wang, MB AF Shay, Sophie Grace Chang, Elena Lewis, Michael S. Wang, Marilene B. TI Characteristics of Human Papillomavirus-Associated Head and Neck Cancers in a Veteran Population SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; QUALITY-OF-LIFE; PHASE-III TRIAL; OROPHARYNGEAL CANCER; UNITED-STATES; ORAL-CANCER; AFRICAN-AMERICANS; TOBACCO SMOKING; INCREASED RISK; HEALTH-STATUS AB IMPORTANCE The US veteran population represents a unique cohort of patients in whom human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) has yet to be investigated. OBJECTIVE To investigate the incidence and characteristics of HPV-positive HNSCC within the veteran population. DESIGN, SETTING, AND PARTICIPANTS Retrospective medical record review including patients with HNSCC diagnosed between January 1, 2010, and November 15, 2013, from the VA Greater Los Angeles Healthcare System. Data were collected between November 16, 2013, and June 19, 2014, and analyzed between June 20, 2014, and March 26, 2015. EXPOSURES Chemoradiation therapy, radiation therapy, surgery, or no treatment. MAIN OUTCOMES AND MEASURES We determined HPV positivity by p16 testing. Demographic and clinicopathologic information and overall survival were extracted from medical records. RESULTS We identified 150 patients with the diagnosis of HNSCC. Sixty-nine patients had HPV-positive tumors (46%), and 65 (43%) had HPV-negative tumors (16 did not have HPV testing). Age at diagnosis ranged from 44 to 94 years (mean, 64.6 [SD, 8.0] years), and median (interquartile range) follow-up was 16.7 (8.7-27.3) years. Tumor location differed significantly between the 2 groups, with an HPV-positive predominance in the oropharynx (43 of 57 [75%]; P <.001). The HPV-positive patients were more likely to be treated primarily with combined chemoradiation therapy than radiation therapy or surgery (P <.001). T4 tumors had a nearly 9 times greater rate of mortality compared with T1 tumors (HR, 8.52 [95% CI, 2.60-18.40; P <.001); N3 disease was associated with 7.18 times greater mortality (HR, 7.18 [95% CI, 1.99-12.26]; P <.001) compared with N1 disease; and M1 disease was associated with 6.0 times greater mortality (HR, 5.99 [95% CI, 2.59-13.81]; P <.001). There were 42 total deaths during follow-up, 25 in the HPV-negative group and 17 in the HPV-positive group, with a nonsignificantly higher overall survival among HPV-positive patients independent of alcohol or tobacco use history (P =.09). CONCLUSIONS AND RELEVANCE Previous studies have found that the proportion of HPV-positive HNSCC in the general population ranges between 20% and 75%. Although the incidence of HPV-positive HNSCC in the Veterans Affairs population is comparable, these patients have unique risk factors and demographic characteristics that may suggest different prognostic factors for HPV-positive HNSCC in this population. Nonetheless, HPV-positive tumors still seem to portend a better overall prognosis regardless of alcohol or tobacco history among the Veterans Affairs population. C1 [Shay, Sophie Grace; Wang, Marilene B.] VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. [Shay, Sophie Grace; Wang, Marilene B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Head & Neck Surg, Los Angeles, CA 90095 USA. [Chang, Elena; Lewis, Michael S.] VA Greater Los Angeles Healthcare Syst, Dept Pathol, Los Angeles, CA USA. RP Wang, MB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Head & Neck Surg, 200 UCLA Med Plaza Ste 550, Los Angeles, CA 90095 USA. EM mbwang@ucla.edu NR 46 TC 2 Z9 2 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6181 EI 2168-619X J9 JAMA OTOLARYNGOL JI JAMA Otolaryngol-Head Neck Surg. PD SEP PY 2015 VL 141 IS 9 BP 790 EP 796 DI 10.1001/jamaoto.2015.1447 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CS0NQ UT WOS:000361758200002 PM 26270931 ER PT J AU Lin, DT Yarlagadda, BB Sethi, RKV Feng, AL Shnayder, Y Ledgerwood, LG Diaz, JA Sinha, P Hanasono, MM Yu, PR Skoracki, RJ Lian, TS Patel, UA Leibowitz, J Purdy, N Starmer, H Richmon, JD AF Lin, Derrick T. Yarlagadda, Bharat B. Sethi, Rosh K. V. Feng, Allen L. Shnayder, Yelizaveta Ledgerwood, Levi G. Diaz, Jason A. Sinha, Parul Hanasono, Matthew M. Yu, Peirong Skoracki, Roman J. Lian, Timothy S. Patel, Urjeet A. Leibowitz, Jason Purdy, Nicholas Starmer, Heather Richmon, Jeremy D. TI Long-term Functional Outcomes of Total Glossectomy With or Without Total Laryngectomy SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; FREE-FLAP RECONSTRUCTION; TONGUE RECONSTRUCTION; HUMAN-PAPILLOMAVIRUS; PRESERVATION; SURVIVAL; CANCER; HEAD AB IMPORTANCE The optimal reconstruction of total glossectomy defects with or without total laryngectomy is controversial. Various pedicled and free tissue flaps have been advocated, but long-term data on functional outcomes are not available to date. OBJECTIVES To compare various total glossectomy defect reconstructive techniques used by multiple institutions and to identify factors that may lead to improved long-term speech and swallowing function. DESIGN, SETTING, AND PARTICIPANTS A multi-institutional, retrospective review of electronic medical records of patients undergoing total glossectomy at 8 participating institutions between June 1, 2001, and June 30, 2011, who had a minimal survival of 2 years. INTERVENTION Total glossectomy with or without total laryngectomy. MAIN OUTCOMES AND MEASURES Demographic and surgical factors were compiled and correlated with speech and swallowing outcomes. RESULTS At the time of the last follow-up, 45%(25 of 55) of patients did not have a gastrostomy tube, and 76%(42 of 55) retained the ability to verbally communicate. Overall, 75%(41 of 55) of patients were tolerating at least minimal nutritional oral intake. Feeding tube dependence was not associated with laryngeal preservation or the reconstructive techniques used, including flap suspension, flap innervation, or type of flap used. Laryngeal preservation was associated with favorable speech outcomes, such as the retained ability to verbally communicate in 97% of those not undergoing total laryngectomy (35 of 36 patients) vs 44%(7 of 16) in those undergoing total laryngectomy (P <.001), as well as those not undergoing total laryngectomy achieving some or all intelligible speech in 85%(29 of 34 patients) compared with 31% (4 of 13) undergoing total laryngectomy achieving the same intelligibility (P <.001). CONCLUSIONS AND RELEVANCE In patients with total glossectomy, feeding tube dependence was not associated with laryngeal preservation or the reconstructive technique, including flap innervation and type of flap used. Laryngeal preservation was associated with favorable speech outcomes such as the retained ability to verbally communicate and higher levels of speech intelligibility. C1 [Lin, Derrick T.; Yarlagadda, Bharat B.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Sethi, Rosh K. V.] Harvard Univ, Sch Med, Boston, MA USA. [Feng, Allen L.; Starmer, Heather; Richmon, Jeremy D.] Johns Hopkins Univ, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21287 USA. [Shnayder, Yelizaveta; Ledgerwood, Levi G.] Univ Kansas, Med Ctr, Dept Otolaryngol Head & Neck Surg, Kansas City, KS USA. [Diaz, Jason A.; Sinha, Parul] Washington Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, St Louis, MO 63110 USA. [Hanasono, Matthew M.; Yu, Peirong; Skoracki, Roman J.] Univ Texas MD Anderson Canc Ctr, Dept Plast Surg, Houston, TX 77030 USA. [Lian, Timothy S.] Louisiana State Univ, Hlth Sci Ctr, Dept Otolaryngol Head & Neck Surg, New Orleans, LA USA. [Patel, Urjeet A.] Northwestern Univ, Dept Otolaryngol Head & Neck Surg, Chicago, IL 60611 USA. [Leibowitz, Jason; Purdy, Nicholas] Univ Miami, Miller Sch Med, Dept Otolaryngol Head & Neck Surg, Miami, FL 33136 USA. RP Richmon, JD (reprint author), Johns Hopkins Univ, Dept Otolaryngol Head & Neck Surg, 601 N Caroline St,Sixth Floor, Baltimore, MD 21287 USA. EM jrichmo7@jhmi.edu NR 22 TC 1 Z9 1 U1 1 U2 2 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 SEP PY 2015 VL 141 IS 9 BP 797 EP 803 DI 10.1001/jamaoto.2015.1463 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CS0NQ UT WOS:000361758200003 PM 26291031 ER PT J AU Pozhidaeva, AK Mohni, KN Dhe-Paganon, S Arrowsmith, CH Weller, SK Korzhnev, DM Bezsonova, I AF Pozhidaeva, Alexandra K. Mohni, Kareem N. Dhe-Paganon, Sirano Arrowsmith, Cheryl H. Weller, Sandra K. Korzhnev, Dmitry M. Bezsonova, Irina TI Structural Characterization of Interaction between Human Ubiquitin-specific Protease 7 and Immediate-Early Protein ICP0 of Herpes Simplex Virus-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SECONDARY STRUCTURE; REGULATORY PROTEIN; P53 STABILIZATION; P53-MDM2 PATHWAY; CHEMICAL-SHIFTS; E3 LIGASE; USP7; HAUSP; USP7/HAUSP; DOMAIN AB Human ubiquitin-specific protease 7 (USP7) is a deubiquitinating enzyme that prevents protein degradation by removing polyubiquitin chains from its substrates. It regulates the stability of a number of human transcription factors and tumor suppressors and plays a critical role in the development of several types of cancer, including prostate and small cell lung cancer. In addition, human USP7 is targeted by several viruses of the Herpesviridae family and is required for effective herpesvirus infection. The USP7 C-terminal region (C-USP7) contains five ubiquitin-like domains (UBL1-5) that interact with several USP7 substrates. Although structures of the USP7 C terminus bound to its substrates could provide vital information for understanding USP7 substrate specificity, no such data has been available to date. In this work we have demonstrated that the USP7 ubiquitin-like domains can be studied in isolation by solution NMR spectroscopy, and we have determined the structure of the UBL1 domain. Furthermore, we have employed NMR and viral plaque assays to probe the interaction between the C-USP7 and HSV-1 immediate-early protein ICP0 (infected cell protein 0), which is essential for efficient lytic infection and virus reactivation from latency. We have shown that depletion of the USP7 in HFF-1 cells negatively affects the efficiency of HSV-1 lytic infection. We have also found that USP7 directly binds ICP0 via its C-terminal UBL1-2 domains and mapped the USP7-binding site for ICP0. Therefore, this study represents a first step toward understanding the molecular mechanism of C-USP7 specificity toward its substrates and may provide the basis for future development of novel antiviral and anticancer therapies. C1 [Pozhidaeva, Alexandra K.; Weller, Sandra K.; Korzhnev, Dmitry M.; Bezsonova, Irina] Univ Connecticut Hlth, Dept Mol Biol & Biophys, Farmington, CT 06030 USA. [Mohni, Kareem N.] Vanderbilt Univ, Med Ctr, Dept Biochem, Nashville, TN 37232 USA. [Dhe-Paganon, Sirano] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Arrowsmith, Cheryl H.] Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L7, Canada. RP Bezsonova, I (reprint author), Univ Connecticut Hlth, Dept Mol Biol & Biophys, 263 Farmington Ave, Farmington, CT 06030 USA. EM bezsonova@uchc.edu FU Charles H. Hood Foundation; State of Connecticut Department of Public Health Biomedical Research Grant FX This work was supported by a Charles H. Hood Foundation child health research award and a State of Connecticut Department of Public Health Biomedical Research Grant (to I. B.). The authors declare that they have no conflicts of interest with the contents of this article. NR 58 TC 2 Z9 2 U1 1 U2 15 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 SEP PY 2015 VL 290 IS 38 BP 22907 EP 22918 DI 10.1074/jbc.M115.664805 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CR9OE UT WOS:000361685500004 PM 26224631 ER PT J AU Jayakar, SS Zhou, XJ Savechenkov, PY Chiara, DC Desai, R Bruzik, KS Miller, KW Cohen, JB AF Jayakar, Selwyn S. Zhou, Xiaojuan Savechenkov, Pavel Y. Chiara, David C. Desai, Rooma Bruzik, Karol S. Miller, Keith W. Cohen, Jonathan B. TI Positive and Negative Allosteric Modulation of an alpha 1 beta 3 gamma 2 gamma-Aminobutyric Acid Type A (GABA(A))Receptor by Binding to a Site in the Transmembrane Domain at the gamma(+)-beta(-) Interface SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTOR; CYS-LOOP RECEPTORS; GATED ION CHANNELS; GABA(A) RECEPTOR; AMINO-ACID; PHOTOREACTIVE BARBITURATE; HEXAFLUORODIETHYL ETHER; SUBUNIT INTERFACES; ETOMIDATE SITES; CONVULSANT AB In the process of developing safer general anesthetics, isomers of anesthetic ethers and barbiturates have been discovered that act as convulsants and inhibitors of gamma-aminobutyric acid type A receptors (GABA(A)Rs) rather than potentiators. It is unknown whether these convulsants act as negative allosteric modulators by binding to the intersubunit anesthetic-binding sites in the GABA(A)R transmembrane domain (Chiara, D. C., Jayakar, S. S., Zhou, X., Zhang, X., Savechenkov, P. Y., Bruzik, K. S., Miller, K. W., and Cohen, J. B. (2013) J. Biol. Chem. 288, 19343-19357) or to known convulsant sites in the ion channel or extracellular domains. Here, we show that S-1-methyl-5-propyl-5-(m-trifluoromethyl-diazirynylphenyl) barbituric acid (S-mTFD-MPPB), a photoreactive analog of the convulsant barbiturate S-MPPB, inhibits alpha 1 beta 3 gamma 2 but potentiates alpha 1 beta 3 GABA(A)R responses. In the alpha 1 beta 3 gamma 2 GABA(A)R, S-mTFD-MPPB binds in the transmembrane domain with high affinity to the gamma(+)-beta(-) subunit interface site with negative energetic coupling to GABA binding in the extracellular domain at the beta(+)-alpha(-) subunit interfaces. GABA inhibits S-[H-3] mTFD-MPPB photolabeling of gamma 2Ser-280 (gamma M2-15') in this site. In contrast, within the same site GABA enhances photolabeling of beta 3Met-227 in beta M1 by an anesthetic barbiturate, R-[H-3] methyl-5-allyl-5-(m-trifluoromethyl-diazirynylphenyl) barbituric acid (mTFD-MPAB), which differs from S-mTFD-MPPB in structure only by chirality and two hydrogens (propyl versus allyl). S-mTFD-MPPB and R-mTFD-MPAB are predicted to bind in different orientations at the gamma(+)-beta(-) site, based upon the distance in GABA(A)R homology models between gamma 2Ser-280 and beta 3Met-227. These results provide an explanation for S-mTFD-MPPB inhibition of alpha 1 beta 3 gamma 2 GABA(A)R function and provide a first demonstration that an intersubunit-binding site in the GABA(A)R transmembrane domain binds negative and positive allosteric modulators. C1 [Jayakar, Selwyn S.; Chiara, David C.; Cohen, Jonathan B.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Miller, Keith W.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Zhou, Xiaojuan; Desai, Rooma; Miller, Keith W.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Savechenkov, Pavel Y.; Bruzik, Karol S.] Univ Illinois, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA. RP Cohen, JB (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. EM jonathan_cohen@hms.harvard.edu FU National Institutes of Health from USPHS [GM-58448] FX This work was supported, in whole or in part, by National Institutes of Health Grant GM-58448 from USPHS. The authors declare that they have no conflicts of interest with the contents of the article. NR 48 TC 4 Z9 4 U1 0 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 SEP PY 2015 VL 290 IS 38 BP 23432 EP 23446 DI 10.1074/jbc.M115.672006 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CR9OE UT WOS:000361685500047 PM 26229099 ER PT J AU Lee, SH Hayano, K Zhu, AX Sahani, DV Yoshida, H AF Lee, Sang Ho Hayano, Koichi Zhu, Andrew X. Sahani, Dushyant V. Yoshida, Hiroyuki TI Advanced Hepatocellular Carcinoma: Perfusion Computed Tomography-Based Kinetic Parameter as a Prognostic Biomarker for Prediction of Patient Survival SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE antiangiogenic chemotherapy; hepatocellular carcinoma; imaging biomarker; perfusion CT; TK - Tofts-Kety; 2CX-2-compartment exchange; AATH - adiabatic approximation to the tissue homogeneity; DP - distributed parameter; AIF - arterial input function; BF - blood flow; BV - blood volume; MTT - mean transit time; PS - permeability-surface area product; v(I) - fractional interstitial volume; E- extraction fraction ID SQUAMOUS-CELL CARCINOMA; CONTRAST-ENHANCED CT; ANTIANGIOGENIC THERAPIES; CAPILLARY-PERMEABILITY; INITIAL-EXPERIENCE; TUMOR PERFUSION; TISSUE; MODEL; TRACER; ANGIOGENESIS AB Objective The aim of this study was to find prognostic biomarkers in perfusion computed tomography (PCT)-based kinetic parameters for advanced hepatocellular carcinoma (HCC) treated with antiangiogenic chemotherapy. Methods Twenty-two patients with advanced HCC underwent PCT imaging and subsequently received bevacizumab in combination with gemcitabine and oxaliplatin. Pretreatment PCT data within advanced HCC were analyzed using the Tofts-Kety, 2-compartment exchange, adiabatic approximation to the tissue homogeneity (AATH), and distributed parameter models. Blood flow, blood volume, extraction fraction (E), and other 3 parameters were calculated. Kinetic parameters in each model were evaluated with 1-year survival discrimination using Kaplan-Meier analysis and with overall survival using univariate Cox regression analysis. Results Only the AATH model-derived E was statistically significantly prognostic for 1-year survival. The increased AATH model-derived E was significantly associated with longer overall survival (P = 0.005). Conclusions The AATH model-derived E was an effective prognostic biomarker for advanced HCC. C1 [Lee, Sang Ho; Yoshida, Hiroyuki] Massachusetts Gen Hosp, Dept Radiol, Imaging Res 3D, Boston, MA 02114 USA. [Lee, Sang Ho; Yoshida, Hiroyuki] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hayano, Koichi; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Zhu, Andrew X.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Yoshida, H (reprint author), Massachusetts Gen Hosp, Dept Radiol, Imaging Res 3D, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. EM yoshida.hiro@mgh.harvard.edu RI Lee, Sang Ho/B-9149-2017 OI Lee, Sang Ho/0000-0002-4634-4904 FU National Institutes of Health [R21CA187877] FX Part of this work was supported by the National Institutes of Health grant of R21CA187877 (principal investigator: H.Y.). NR 61 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 0363-8715 EI 1532-3145 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 2015 VL 39 IS 5 BP 687 EP 696 DI 10.1097/RCT.0000000000000288 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CS0LK UT WOS:000361750700008 PM 26222909 ER PT J AU Aizer, AA Du, R Wen, PY Arvold, ND AF Aizer, Ayal A. Du, Rose Wen, Patrick Y. Arvold, Nils D. TI Radiotherapy and death from cerebrovascular disease in patients with primary brain tumors SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Cancer; Stroke; Death; Location; Radiation ID CHILDHOOD-CANCER SURVIVOR; STAGE BREAST-CANCER; VESSEL OCCLUSIVE VASCULOPATHY; BASILAR ARTERY-OCCLUSION; RADIATION-THERAPY; PITUITARY-ADENOMA; RISK-FACTORS; STROKE; MORTALITY; IRRADIATION AB Radiotherapy is often used in the management of primary brain tumors, but late cerebrovascular risks remain incompletely characterized. We examined the relationship between radiotherapy and the risk of death from cerebrovascular disease (CVD) in this population. We used the Surveillance, Epidemiology, and End Results Program to identify 19,565 patients of any age diagnosed with a primary brain tumor between 1983-2002. Multivariable competing risks analysis and an interaction model were used to determine whether receipt of radiotherapy was associated with an increased risk of CVD-specific death, adjusting for tumor proximity to central arterial circulations of the brain. The median follow up in surviving patients was 12.75 years. Baseline characteristics were similar in patients who did and did not receive radiotherapy. Ten-year CVD-specific mortality in patients with tumors near central arterial circulations who did and did not receive radiotherapy were 0.64 % (95 % CI 0.42-0.93 %) versus 0.16 % (95 % CI 0.055-0.40 %), p = 0.01. After adjustment for demographic, tumor-related, and treatment-related covariates, patients with tumors near central arterial circulations were significantly more likely to experience CVD-specific mortality after radiotherapy (HR 2.81; 95 % CI 1.25-6.31; p = 0.01); no association was observed among patients with more distant tumors (HR 0.77; 95 % CI 0.50-1.16; p = 0.21). The interaction model showed that tumor location was a key predictor of the risk of radiotherapy-associated, CVD-specific mortality (p-interaction = 0.004). Patients receiving radiotherapy for tumors near but not distant from the central vasculature of the brain are at increased risk for death secondary to CVD, which should be considered when counseling patients. C1 [Aizer, Ayal A.; Arvold, Nils D.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. [Du, Rose] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02115 USA. RP Arvold, ND (reprint author), Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM narvold@partners.org OI Du, Rose/0000-0003-2641-6496 NR 32 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD SEP PY 2015 VL 124 IS 2 BP 291 EP 297 DI 10.1007/s11060-015-1839-5 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CS2FJ UT WOS:000361883000017 PM 26080799 ER EF