FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Bellad, RM Bang, A Carlo, WA McClure, EM Meleth, S Goco, N Goudar, SS Derman, RJ Hibberd, PL Patel, A Esamai, F Bucher, S Gisore, P Wright, LL AF Bellad, Roopa M. Bang, Akash Carlo, Waldemar A. McClure, Elizabeth M. Meleth, Sreelatha Goco, Norman Goudar, Shivaprasad S. Derman, Richard J. Hibberd, Patricia L. Patel, Archana Esamai, Fabian Bucher, Sherri Gisore, Peter Wright, Linda L. CA HBB Study Grp TI A pre-post study of a multi-country scale up of resuscitation training of facility birth attendants: does Helping Babies Breathe training save lives? SO BMC PREGNANCY AND CHILDBIRTH LA English DT Article ID MIDDLE-INCOME COUNTRIES; MORTALITY; ETHIOPIA; WOMEN AB Background: Whether facility-based implementation of Helping Babies Breathe (HBB) reduces neonatal mortality at a population level in low and middle income countries (LMIC) has not been studied. Therefore, we evaluated HBB implementation in this context where our study team has ongoing prospective outcome data on all pregnancies regardless of place of delivery. Methods: We compared outcomes of birth cohorts in three sites in India and Kenya pre-post implementation of a facility-based intervention, using a prospective, population-based registry in 52 geographic clusters. Our hypothesis was that HBB implementation would result in a 20 % decrease in the perinatal mortality rate (PMR) among births >= 1500 g. Results: We enrolled 70,704 births during two 12-month study periods. Births within each site did not differ pre-post intervention, except for an increased proportion of <2500 g newborns and deliveries by caesarean section in the post period. There were no significant differences in PMR among all registry births; however, a post-hoc analysis stratified by birthweight documented improvement in <2500 g mortality in Belgaum in both registry and in HBB-trained facility births. No improvement in <2500 g mortality measures was noted in Nagpur or Kenya and there was no improvement in normal birth weight survival. Conclusions: Rapid scale up of HBB training of facility birth attendants in three diverse sites in India and Kenya was not associated with consistent improvements in mortality among all neonates >= 1500 g; however, differential improvements in <2500 g survival in Belgaum suggest the need for careful implementation of HBB training with attention to the target population, data collection, and ongoing quality monitoring activities. C1 [Bellad, Roopa M.; Goudar, Shivaprasad S.] KLE Univ Jawaharlal Nehru Med Coll, Belgaum, Karnataka, India. [Bang, Akash] Mahatma Gandhi Inst Med Sci, Sevagram, Maharashtra, India. [Carlo, Waldemar A.] Univ Alabama Birmingham, Birmingham, AL USA. [McClure, Elizabeth M.; Meleth, Sreelatha; Goco, Norman] RTI Int, Durham, NC USA. [Derman, Richard J.] Christiana Care Hlth Syst, Dept Obstet & Gynecol, Newark, DE USA. [Hibberd, Patricia L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Patel, Archana] Lata Med Res Fdn, Nagpur, Maharashtra, India. [Patel, Archana] Indira Gandhi Govt Med Coll, Nagpur, Maharashtra, India. [Esamai, Fabian; Gisore, Peter] Moi Univ Sch Med, Dept Child Hlth & Paediat, Eldoret, Kenya. [Bucher, Sherri] Indiana Univ, Sch Med, Indianapolis, IN USA. [Wright, Linda L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. [Wright, Linda L.] 5800 Nicholson Lane,1206, Rockville, MD 20852 USA. RP Wright, LL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.; Wright, LL (reprint author), 5800 Nicholson Lane,1206, Rockville, MD 20852 USA. EM lindawright.md@gmail.com OI Somannavar, Manjunath/0000-0002-8871-5072 FU Norad; Laerdal Foundation; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) FX The study was funded by grants from Norad, Laerdal Foundation and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). NICHD staff had input into the study design, data interpretation and writing of the report. RTI staff had access to all the study data. The corresponding author wrote the first draft of the manuscript and had final responsibility for the decision to submit for publication. NR 17 TC 1 Z9 1 U1 6 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2393 J9 BMC PREGNANCY CHILDB JI BMC Pregnancy Childbirth PD AUG 15 PY 2016 VL 16 AR 222 DI 10.1186/s12884-016-0997-6 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DT4UL UT WOS:000381476500001 PM 27527831 ER PT J AU Figlewicz, DP AF Figlewicz, Dianne P. TI Expression of receptors for insulin and leptin in the ventral tegmental area/substantia nigra (VTA/SN) of the rat: Historical perspective SO BRAIN RESEARCH LA English DT Review DE Dopamine; Fluorescence immunocytochemistry; Reward; Ingestive behavior ID HIGH-FAT DIET; INTRAVENTRICULAR INSULIN; FOOD-DEPRIVATION; MESSENGER-RNA; DOPAMINE TRANSPORTER; PLACE PREFERENCE; ENERGY-BALANCE; BRAIN; INCREASES; REWARD AB Since the publication of the observation that dopaminergic neurons in the ventral tegmental area/substantia nigra of the rat express receptors for insulin and leptin, numerous studies have extended and validated these findings. Thus, these major metabolic hormones have effects on synaptic and cell signaling function of the midbrain dopamine neurons, across a range of concentrations that reflect physiologic (fasting vs. fed) and pathophysiologic (diabetes) circumstances. The capacity of metabolic hormones to alter reward behaviors, including palatability-related food intake; motivation for food; and the conditioning of place preference by food, is now appreciated as an integral part of the larger actions of these hormones to regulate caloric homeostasis. Finally, the delineation of metabolic hormone effects on the CNS reward circuitry of normal animals provides the rationale and experimental basis for evaluating dysfunction of reward circuitry in obesity and diabetes. This article is part-of a Special Issue entitled SI:50th Anniversary Issue. Published by Elsevier B.V. C1 [Figlewicz, Dianne P.] VA Puget Sound Hlth Care Syst, BSLRD, Seattle, WA 98108 USA. [Figlewicz, Dianne P.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Figlewicz, DP (reprint author), VAPSHCS 151, 1660 So Columbian Way, Seattle, WA 98108 USA. EM latte@uw.edu FU VA Puget Sound Health Care System, Seattle, Washington; NIH [DK40963]; American Recovery and Reinvestment Act (ARRA) [NIH DK 40963] FX I particularly thank my colleagues of many years, Dr. Patti Szot and Dr. Al Sipols. Their assistance and advice made the completion of all the studies described here possible. I thank again the coauthors of the original study, Dr. Scott Ng-Evans, a postdoctoral fellow in the lab; Dr. Denis Baskin, a long-time colleague and collaborator; and Marcy Hoen and Joyce Murphy, who provided expert technical assistance. Dianne Figlewicz Lattemann is a Senior Research Career Scientist, Biomedical Laboratory Research Program, Department of Veterans Affairs Puget Sound Health Care System, Seattle, Washington. The author's research described in this article is the result of work supported by resources from the VA Puget Sound Health Care System, Seattle, Washington, and was supported by NIH grant DK40963 and by the American Recovery and Reinvestment Act (ARRA) (Grant No. NIH DK 40963). NR 29 TC 1 Z9 1 U1 4 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD AUG 15 PY 2016 VL 1645 SI SI BP 68 EP 70 DI 10.1016/j.brainres.2015.12.041 PG 3 WC Neurosciences SC Neurosciences & Neurology GA DT5QJ UT WOS:000381537400021 PM 26731335 ER PT J AU Stopsack, KH Gerke, TA Sinnott, JA Penney, KL Tyekucheva, S Sesso, HD Andersson, SO Andren, O Cerhan, JR Giovannucci, EL Mucci, LA Rider, JR AF Stopsack, Konrad H. Gerke, Travis A. Sinnott, Jennifer A. Penney, Kathryn L. Tyekucheva, Svitlana Sesso, Howard D. Andersson, Swen-Olof Andren, Ove Cerhan, James R. Giovannucci, Edward L. Mucci, Lorelei A. Rider, Jennifer R. TI Cholesterol Metabolism and Prostate Cancer Lethality SO CANCER RESEARCH LA English DT Article ID INTRATUMORAL ANDROGENS; CARDIOVASCULAR-DISEASE; SQUALENE EPOXIDASE; GENE-EXPRESSION; BETA-CAROTENE; RISK; PROGRESSION; HYPERCHOLESTEROLEMIA; ANGIOGENESIS; ASSOCIATION AB Cholesterol metabolism has been implicated in prostate cancer pathogenesis. Here, we assessed the association of intratumoral mRNA expression of cholesterol synthesis enzymes, transporters, and regulators in tumor specimen at diagnosis and lethal prostate cancer, defined as mortality or metastases from prostate cancer in contrast to nonlethal disease without evidence of metastases after at least 8 years of follow-up. We analyzed the prospective prostate cancer cohorts within the Health Professionals Follow-up Study (n = 249) and the Physicians' Health Study (n = 153) as well as expectantly managed patients in the Swedish Watchful Waiting Study (n = 338). The expression of squalene monooxygenase (SQLE) was associated with lethal cancer in all three cohorts. Men with high SQLE expression (>1 standard deviation above the mean) were 8.3 times (95% confidence interval, 3.5 to 19.7) more likely to have lethal cancer despite therapy compared with men with the mean level of SQLE expression. Absolute SQLE expression was associated with lethal cancer independently from Gleason grade and stage, as was a SQLE expression ratio in tumor versus surrounding benign prostate tissue. Higher SQLE expression was tightly associated with increased histologic markers of angiogenesis. Collectively, this study establishes the prognostic value of intratumoral cholesterol synthesis as measured via SQLE, its second rate-limiting enzyme. SQLE expression at cancer diagnosis is prognostic for lethal prostate cancer both after curative-intent prostatectomy and in a watchful waiting setting, possibly by facilitating micrometastatic disease. (C) 2016 AACR. C1 [Stopsack, Konrad H.; Gerke, Travis A.; Sinnott, Jennifer A.; Penney, Kathryn L.; Sesso, Howard D.; Giovannucci, Edward L.; Mucci, Lorelei A.; Rider, Jennifer R.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Stopsack, Konrad H.] Mayo Clin, Dept Internal Med, 200 1st St SW, Rochester, MN 55905 USA. [Gerke, Travis A.] Univ Florida, Coll Med, Dept Epidemiol, Gainesville, FL USA. [Gerke, Travis A.] Univ Florida, Coll Publ Hlth & Hlth Profess, Gainesville, FL USA. [Sinnott, Jennifer A.] Ohio State Univ, Dept Stat, Columbus, OH 43210 USA. [Penney, Kathryn L.; Giovannucci, Edward L.; Mucci, Lorelei A.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Penney, Kathryn L.; Giovannucci, Edward L.; Mucci, Lorelei A.] Harvard Med Sch, Boston, MA USA. [Tyekucheva, Svitlana] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Tyekucheva, Svitlana] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA. [Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Aging, 75 Francis St, Boston, MA 02115 USA. [Andersson, Swen-Olof; Andren, Ove] Univ Orebro, Sch Hlth & Med Sci, Dept Urol, Orebro, Sweden. [Cerhan, James R.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Giovannucci, Edward L.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Rider, Jennifer R.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Stopsack, KH (reprint author), Mayo Clin, Dept Internal Med, 200 1st St SW, Rochester, MN 55905 USA. EM stopsack@post.harvard.edu FU NCI NIH HHS [R01 CA097193, P01 CA055075, P50 CA090381, R01 CA034944, R01 CA034944-03, R01 CA040360, R01 CA133891, R01 CA141298, T32 CA009001, UM1 CA167552]; NHLBI NIH HHS [R01 HL026490, R01 HL026490-03, R01 HL034595, R01 HL034595-07] NR 32 TC 1 Z9 1 U1 3 U2 3 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 AUG 15 PY 2016 VL 76 IS 16 BP 4785 EP 4790 DI 10.1158/0008-5472.CAN-16-0903 PG 6 WC Oncology SC Oncology GA DU6BI UT WOS:000382297700020 PM 27325648 ER PT J AU Li, J Shin, S Sun, Y Yoon, SO Li, CG Zhang, E Yu, J Zhang, JM Blenis, J AF Li, Jing Shin, Sejeong Sun, Yang Yoon, Sang-Oh Li, Chenggang Zhang, Erik Yu, Jane Zhang, Jianming Blenis, John TI mTORC1-Driven Tumor Cells Are Highly Sensitive to Therapeutic Targeting by Antagonists of Oxidative Stress SO CANCER RESEARCH LA English DT Article ID TUBEROUS SCLEROSIS COMPLEX; BUTHIONINE SULFOXIMINE; GLUTATHIONE SYNTHESIS; CANCER-CELLS; NULL-CELLS; METABOLISM; AUTOPHAGY; ACTIVATION; MECHANISMS; SURVIVAL AB mTORC1 is a central signaling node in controlling cell growth, proliferation, and metabolism that is aberrantly activated in cancers and certain cancer-associated genetic disorders, such as tuberous sclerosis complex (TSC) and sporadic lymphangioleiomyomatosis. However, while mTORC1-inhibitory compounds (rapamycin and rapalogs) attracted interest as candidate therapeutics, clinical trials have not replicated the promising findings in preclinical models, perhaps because these compounds tend to limit cell proliferation without inducing cell death. In seeking to address this issue, we performed a high-throughput screen for small molecules that could heighten the cytotoxicity of mTORC1 inhibitors. Here we report the discovery that combining inhibitors of mTORC1 and glutamate cysteine ligase (GCLC) can selectively and efficiently trigger apoptosis in Tsc2-deficient cells but not wild-type cells. Mechanistic investigations revealed that coinhibition of mTORC1 and GCLC decreased the level of the intracellular thiol antioxidant glutathione (GSH), thereby increasing levels of reactive oxygen species, which we determined to mediate cell death in Tsc2-deficient cells. Our findings offer preclinical proof of concept for a strategy to selectively increase the cytotoxicity of mTORC1 inhibitors as a therapy to eradicate tumor cells marked by high mTORC1 signaling, based on cotargeting a GSH-controlled oxidative stress pathway. (C) 2016 AACR. C1 [Li, Jing; Blenis, John] Harvard Med Sch, Dept Cell Biol, Boston, MA USA. [Shin, Sejeong; Yoon, Sang-Oh; Blenis, John] Weill Cornell Med, Dept Pharmacol, Meyer Canc Ctr, New York, NY USA. [Li, Chenggang; Zhang, Erik; Yu, Jane] Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA. [Sun, Yang; Li, Chenggang; Zhang, Erik; Yu, Jane] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Zhang, Jianming] Massachusetts Gen Hosp, Dept Dermatol, Charlestown, MA USA. RP Blenis, J (reprint author), Weill Cornell Med, Meyer Canc Ctr, 413 East 69th St, New York, NY 10021 USA. EM job2064@med.cornell.edu FU NHLBI NIH HHS [R01 HL121266, R01 HL098216]; NIDDK NIH HHS [R01 DK098331]; NIGMS NIH HHS [R01 GM051405] NR 39 TC 3 Z9 3 U1 6 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 2016 VL 76 IS 16 BP 4816 EP 4827 DI 10.1158/0008-5472.CAN-15-2629 PG 12 WC Oncology SC Oncology GA DU6BI UT WOS:000382297700023 PM 27197195 ER PT J AU Menard, JA Christianson, HC Kucharzewska, P Bourseau-Guilmain, E Svensson, KJ Lindqvist, E Chandran, VI Kjellen, L Welinder, C Bengzon, J Johansson, MC Belting, M AF Menard, Julien A. Christianson, Helena C. Kucharzewska, Paulina Bourseau-Guilmain, Erika Svensson, Katrin J. Lindqvist, Eva Chandran, Vineesh Indira Kjellen, Lena Welinder, Charlotte Bengzon, Johan Johansson, Maria C. Belting, Mattias TI Metastasis Stimulation by Hypoxia and Acidosis-Induced Extracellular Lipid Uptake Is Mediated by Proteoglycan-Dependent Endocytosis SO CANCER RESEARCH LA English DT Article ID HEPARAN-SULFATE PROTEOGLYCANS; TUMOR MICROENVIRONMENT; CANCER METABOLISM; CELLS; LIPOPROTEINS; MACROPHAGES; RECEPTOR; SITES; LDL; PHENOTYPE AB Hypoxia and acidosis are inherent stress factors of the tumor microenvironment and have been linked to increased tumor aggressiveness and treatment resistance. Molecules involved in the adaptive mechanisms that drive stress-induced disease progression constitute interesting candidates of therapeutic intervention. Here, we provide evidence of a novel role of heparan sulfate proteoglycans (HSPG) in the adaptive response of tumor cells to hypoxia and acidosis through increased internalization of lipoproteins, resulting in a lipid-storing phenotype and enhanced tumor-forming capacity. Patient glioblastoma tumors and cells under hypoxic and acidic stress acquired a lipid droplet (LD)-loaded phenotype, and showed an increased recruitment of all major lipoproteins, HDL, LDL, and VLDL. Stress-induced LD accumulation was associated with increased spheroid-forming capacity during reoxygenation in vitro and lung metastatic potential in vivo. On a mechanistic level, we found no apparent effect of hypoxia on HSPGs, whereas lipoprotein receptors (VLDLR and SR-B1) were transiently upregulated by hypoxia. Importantly, however, using pharmacologic and genetic approaches, we show that stress-mediated lipoprotein uptake is highly dependent on intact HSPG expression. The functional relevance of HSPG in the context of tumor cell stress was evidenced by HSPG-dependent lipoprotein cell signaling activation through the ERK/MAPK pathway and by reversal of the LD-loaded phenotype by targeting of HSPGs. We conclude that HSPGs may have an important role in the adaptive response to major stress factors of the tumor microenvironment, with functional consequences on tumor cell signaling and metastatic potential. (C) 2016 AACR. C1 [Menard, Julien A.; Christianson, Helena C.; Kucharzewska, Paulina; Bourseau-Guilmain, Erika; Lindqvist, Eva; Chandran, Vineesh Indira; Welinder, Charlotte; Johansson, Maria C.; Belting, Mattias] Lund Univ, Sect Oncol & Pathol, Dept Clin Sci, Barngatan 2B, SE-22185 Lund, Sweden. [Svensson, Katrin J.] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. [Svensson, Katrin J.] Harvard Med Sch, Dept Cell Biol, Boston, MA USA. [Kjellen, Lena] Uppsala Univ, Dept Med Biochem & Microbiol, Sci Life Lab, Uppsala, Sweden. [Welinder, Charlotte] Lund Univ, Ctr Excellence Biol & Med Mass Spectrometry CEBMM, Biomed Ctr D13, Lund, Sweden. [Bengzon, Johan] Lund Univ, Lund Stem Cell Ctr, Lund, Sweden. [Bengzon, Johan] Lund Univ, Sect Neurosurg, Dept Clin Sci, Lund, Sweden. [Belting, Mattias] Skane Univ Hosp, Lund, Sweden. RP Belting, M (reprint author), Lund Univ, Sect Oncol & Pathol, Dept Clin Sci, Barngatan 2B, SE-22185 Lund, Sweden. EM Mattias.Belting@med.lu.se OI Welinder, Charlotte/0000-0001-9626-0576 NR 50 TC 0 Z9 0 U1 7 U2 7 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 AUG 15 PY 2016 VL 76 IS 16 BP 4828 EP 4840 DI 10.1158/0008-5472.CAN-15-2831 PG 13 WC Oncology SC Oncology GA DU6BI UT WOS:000382297700024 PM 27199348 ER PT J AU Choi, JW Yoon, KH Yun, SH AF Choi, Jin Woo Yoon, Kwon-Ha Yun, Seok Hyun TI Antimetastatic Effect by Targeting CTC Cluster-Response SO CANCER RESEARCH LA English DT Letter ID PLASMINOGEN-ACTIVATOR SYSTEM; CIRCULATING TUMOR-CELLS; INVASION C1 [Choi, Jin Woo] Wonkwang Univ, Sch Dent, Wonkwang Inst Integrat Biomed Sci, Iksan, Jeonbuk, South Korea. [Choi, Jin Woo] Wonkwang Univ, Sch Dent, Dent Res Inst, Iksan, Jeonbuk, South Korea. [Yoon, Kwon-Ha] Wonkwang Univ, Sch Med, Dept Radiol, Iksan, Jeonbuk, South Korea. [Yun, Seok Hyun] Harvard Med Sch, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA. RP Yoon, KH (reprint author), Wonkwang Univ, Sch Med, Dept Radiol, Iksan, Jeonbuk, South Korea.; Yun, SH (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA.; Choi, JW (reprint author), Wonkwang Univ, Iksan 54538, Chonbuk, South Korea. EM jinwoochoi@wku.ac.kr; khy1646@wonkwang.ac.kr; syun@hms.harvard.edu FU NCI NIH HHS [R01 CA192878]; NIBIB NIH HHS [P41 EB015903] NR 4 TC 0 Z9 0 U1 8 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 2016 VL 76 IS 16 BP 4910 EP 4910 DI 10.1158/0008-5472.CAN-16-0974 PG 1 WC Oncology SC Oncology GA DU6BI UT WOS:000382297700033 PM 27528582 ER PT J AU John, MD Greene, M Hessol, NA Zepf, R Parrott, AH Foreman, C Bourgeois, J Gandhi, M Hare, CB AF John, Malcolm D. Greene, Meredith Hessol, Nancy A. Zepf, Roland Parrott, Amanda Hutton Foreman, Cameron Bourgeois, James Gandhi, Monica Hare, C. Bradley TI Geriatric Assessments and Association With VACS Index Among HIV-Infected Older Adults in San Francisco SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE functional status; geriatrics; HIV; mental health; and social support ID VETERANS AGING COHORT; HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL THERAPY; AIDS; FRAILTY; AGE; DISEASE; RISK; PERFORMANCE; IMPAIRMENT AB Objectives:To perform geriatric assessments in older HIV-infected adults in San Francisco and examine the association with age and the Veterans Aging Cohort Study (VACS) index scores.Methods:A cross-sectional study was conducted from 2012 to 2014 among HIV-infected patients 50 years at 2 San Francisco-based HIV clinics. We evaluated 4 health domains: (1) physical health and function (activities of daily living), instrumental activities of daily living (IADL), falls, gait speed, (2) social support (physical and perceived support, loneliness), (3) mental health (depression, anxiety, posttraumatic stress disorder) and cognition, and (4) behavioral and general health (antiretroviral adherence and quality of life). Contingency table and rank-sum analyses examined associations between these domains with age and VACS index scores.Results:Three hundred fifty-nine patients completed assessments (median age 57; 85% male; 57% white; 72% >high school education). On functional assessment, 39% reported dependence with 1 IADL, and 40% reported falls in the previous year. Fifty-eight percent experienced loneliness, 60% the lowest levels of perceived social support, 55% depression, and 12% posttraumatic stress disorder. Forty percent had possible mild cognitive impairment. Thirty percent reported poor or fair quality of life. Older age was associated with lower CD4 counts, balance problems, slower gait, lower anxiety, poorer general health, and higher antiretroviral adherence. VACS Index score was associated with dependence in 1 IADL and antiretroviral adherence.Conclusion:In a large sample of older HIV-infected adults, multiple significant aging-related conditions were identified. Integrating geriatric assessment tools into HIV/AIDS clinical care may help target interventions to optimize clinical care and quality of life for older HIV-infected individuals. C1 [John, Malcolm D.; Hessol, Nancy A.; Zepf, Roland; Parrott, Amanda Hutton; Foreman, Cameron; Gandhi, Monica; Hare, C. Bradley] Univ Calif San Francisco, Dept Med, Div Infect Dis, San Francisco, CA USA. [Greene, Meredith] Univ Calif San Francisco, Div Geriatr, Dept Med, San Francisco, CA USA. [Greene, Meredith] San Francisco VA Med Ctr, Sect Geriatr & Palliat Med, San Francisco, CA USA. [Hessol, Nancy A.] Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94143 USA. [Bourgeois, James] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Hare, C. Bradley] Kaiser Permanente Med Grp San Francisco Med Ctr, Div Infect Dis, San Francisco, CA USA. RP John, MD (reprint author), 350 Parnassus Ave,Suite 908 Box 0378, San Francisco, CA 94143 USA. EM Malcolm.John@ucsf.edu FU University of California HIV/AIDS Research Program (CHRP) [A116894]; National Institutes of Health [5-T32-AG000212]; NIA at the NIH [P30AG044281] FX This research was funded by grant number A116894 from the University of California HIV/AIDS Research Program (CHRP). M.G. received salary support from the National Institutes of Health (5-T32-AG000212) during this project and receives support from the P30AG044281 from the NIA at the NIH. NR 37 TC 1 Z9 1 U1 4 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD AUG 15 PY 2016 VL 72 IS 5 BP 534 EP 541 DI 10.1097/QAI.0000000000001009 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA DT3KC UT WOS:000381378700011 PM 27028497 ER PT J AU Chan, BT Tsai, AC AF Chan, Brian T. Tsai, Alexander C. TI HIV stigma trends in the general population during antiretroviral treatment expansion: analysis of 31 countries in sub-Saharan Africa, 2003-2013 SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT IDWeek CY OCT 08, 2015 CL San Diego, CA DE stigma; Africa; trends ID CLUSTER-RANDOMIZED TRIAL; AIDS-RELATED STIGMA; RURAL UGANDA; INTERNALIZED STIGMA; SOUTH-AFRICA; CAPE-TOWN; SCALE-UP; HIV/AIDS; PEOPLE; ATTITUDES AB Background:HIV-related stigma is associated with increased risk-taking behavior, reduced uptake of HIV testing, and decreased adherence to antiretroviral therapy (ART). Although ART scale-up may reduce HIV-related stigma, the extent to which levels of stigma in the general population have changed during the era of ART scale-up in sub-Saharan Africa is unknown.Methods:Social distance and anticipated stigma were operationalized using standard HIV-related stigma questions contained in the Demographic and Health Surveys and AIDS Indicator Surveys of 31 African countries between 2003 and 2013. We fitted multivariable linear regression models with cluster-correlated robust standard errors and country fixed effects, specifying social distance or anticipated stigma as the dependent variable and year as the primary explanatory variable of interest.Results:We estimated a statistically significant negative association between year and desires for social distance (b = -0.020; P < 0.001; 95% confidence interval: -0.026 to -0.015) but a statistically significant positive association between year and anticipated stigma (b = 0.023; P < 0.001; 95% confidence interval: 0.018 to 0.027). In analyses stratified by HIV prevalence above or below the sample median, declines in social distancing over time were more pronounced among countries with a higher HIV prevalence.Conclusions:Concomitant with ART scale-up in sub-Saharan Africa, anticipated stigma in the general population increased despite a decrease in social distancing toward people living with HIV. Although ART scale-up may help reduce social distancing toward people living with HIV, particularly in high-prevalence countries, other interventions targeting symbolic or instrumental concerns about HIV may be needed. C1 [Chan, Brian T.] Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA. [Chan, Brian T.; Tsai, Alexander C.] Harvard Med Sch, Boston, MA USA. [Tsai, Alexander C.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Tsai, Alexander C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Tsai, Alexander C.] Mbarara Univ Sci & Technol, Mbarara, Uganda. RP Chan, BT (reprint author), Brigham & Womens Hosp, 15 Francis St,PBBA 4, Boston, MA 02115 USA. EM bchan@partners.org FU NCATS NIH HHS [KL2 TR001100]; NIMH NIH HHS [K23 MH096620] NR 63 TC 2 Z9 2 U1 4 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD AUG 15 PY 2016 VL 72 IS 5 BP 558 EP 564 DI 10.1097/QAI.0000000000001011 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA DT3KC UT WOS:000381378700015 PM 27035888 ER PT J AU Hensley, K Poteshkina, A Johnson, MF Eslami, P Gabbita, SP Hristov, AM Venkova-Hristova, KM Harris-White, ME AF Hensley, Kenneth Poteshkina, Aleksandra Johnson, Ming F. Eslami, Pirooz Gabbita, S. Prasad Hristov, Alexandar M. Venkova-Hristova, Kalina M. Harris-White, Marni E. TI Autophagy Modulation by Lanthionine Ketimine Ethyl Ester Improves Long-Term Outcome after Central Fluid Percussion Injury in the Mouse SO JOURNAL OF NEUROTRAUMA LA English DT Article DE autophagy; behavior; diffuse axon injury; pathology ID TRAUMATIC BRAIN-INJURY; DIFFUSE AXONAL INJURY; NEURONAL CELL-DEATH; CLOSED-HEAD INJURY; CAENORHABDITIS-ELEGANS; ALZHEIMERS-DISEASE; NEUROFILAMENT COMPACTION; MAMMALIAN TARGET; RAPAMYCIN MTOR; NERVE-FIBERS AB Diffuse axonal injury is recognized as a progressive and long-term consequence of traumatic brain injury. Axonal injury can have sustained negative consequences on neuronal functions such as anterograde and retrograde transport and cellular processes such as autophagy that depend on cytoarchitecture and axon integrity. These changes can lead to somatic atrophy and an inability to repair and promote plasticity. Obstruction of the autophagic process has been noted after brain injury, and rapamycin, a drug used to stimulate autophagy, has demonstrated positive effects in brain injury models. The optimization of drugs to promote beneficial autophagy without negative side effects could be used to attenuate traumatic brain injury and promote improved outcome. Lanthionine ketimine ethyl ester, a bioavailable derivative of a natural sulfur amino acid metabolite, has demonstrated effects on autophagy both in vitro and in vivo. Thirty minutes after a moderate central fluid percussion injury and throughout the survival period, lanthionine ketimine ethyl ester was administered, and mice were subsequently evaluated for learning and memory impairments and biochemical and histological changes over a 5-week period. Lanthionine ketimine ethyl ester, which we have shown previously to modulate autophagy markers and alleviate pathology and slow cognitive decline in the 3 x TgAD mouse model, spared cognition and pathology after central fluid percussion injury through a mechanism involving autophagy modulation. C1 [Hensley, Kenneth; Hristov, Alexandar M.; Venkova-Hristova, Kalina M.] Univ Toledo, Dept Pathol, Hlth Sci Campus, Toledo, OH USA. [Hensley, Kenneth] Univ Toledo, Dept Neurosci, Hlth Sci Campus, Toledo, OH USA. [Gabbita, S. Prasad] P2D Biosci Inc, Cincinnati, OH USA. [Poteshkina, Aleksandra; Johnson, Ming F.; Eslami, Pirooz; Harris-White, Marni E.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Harris-White, Marni E.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, 11301 Wilshire Blvd 151, Los Angeles, CA 90073 USA. RP Harris-White, ME (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, 11301 Wilshire Blvd 151, Los Angeles, CA 90073 USA. EM marni@ucla.edu NR 90 TC 2 Z9 2 U1 3 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD AUG 15 PY 2016 VL 33 IS 16 BP 1501 EP + DI 10.1089/neu.2015.4196 PG 14 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA DU6ED UT WOS:000382305900004 PM 26530250 ER PT J AU Cohen, P Spiegelman, BM AF Cohen, Paul Spiegelman, Bruce M. TI Cell biology of fat storage SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID BROWN ADIPOSE-TISSUE; ENDOTHELIAL GROWTH-FACTOR; NECROSIS-FACTOR-ALPHA; BEIGE FAT; ENERGY-EXPENDITURE; INSULIN-RESISTANCE; ADAPTIVE THERMOGENESIS; GENE-EXPRESSION; OBESITY; ADIPOCYTES AB The worldwide epidemic of obesity and type 2 diabetes has greatly increased interest in the biology and physiology of adipose tissues. Adipose (fat) cells are specialized for the storage of energy in the form of triglycerides, but research in the last few decades has shown that fat cells also play a critical role in sensing and responding to changes in systemic energy balance. White fat cells secrete important hormone-like molecules such as leptin, adiponectin, and adipsin to influence processes such as food intake, insulin sensitivity, and insulin secretion. Brown fat, on the other hand, dissipates chemical energy in the form of heat, thereby defending against hypothermia, obesity, and diabetes. It is now appreciated that there are two distinct types of thermogenic fat cells, termed brown and beige adipocytes. In addition to these distinct properties of fat cells, adipocytes exist within adipose tissue, where they are in dynamic communication with immune cells and closely influenced by innervation and blood supply. This review is intended to serve as an introduction to adipose cell biology and to familiarize the reader with how these cell types play a role in metabolic disease and, perhaps, as targets for therapeutic development. C1 [Cohen, Paul] Rockefeller Univ, Lab Mol Metab, New York, NY 10065 USA. [Spiegelman, Bruce M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Spiegelman, Bruce M.] Harvard Med Sch, Dept Cell Biol, Boston, MA 02115 USA. RP Cohen, P (reprint author), Rockefeller Univ, Lab Mol Metab, New York, NY 10065 USA.; Spiegelman, BM (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.; Spiegelman, BM (reprint author), Harvard Med Sch, Dept Cell Biol, Boston, MA 02115 USA. EM pcohen@rockefeller.edu; bruce_spiegelman@dfci.harvard.edu FU NIDDK NIH HHS [P30 DK020541] NR 57 TC 2 Z9 2 U1 11 U2 13 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD AUG 15 PY 2016 VL 27 IS 16 BP 2523 EP 2527 DI 10.1091/mbc.E15-10-0749 PG 5 WC Cell Biology SC Cell Biology GA DU6OZ UT WOS:000382335800002 PM 27528697 ER PT J AU Liu, YJ Lee, IJ Sun, MZ Lower, CA Runge, KW Ma, JJ Wu, JQ AF Liu, Yajun Lee, I-Ju Sun, Mingzhai Lower, Casey A. Runge, Kurt W. Ma, Jianjie Wu, Jian-Qiu TI Roles of the novel coiled-coil protein Rng10 in septum formation during fission yeast cytokinesis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID GTPASE-ACTIVATING PROTEIN; PHOTOACTIVATABLE FLUORESCENT PROTEINS; ALPHA-GLUCAN BIOSYNTHESIS; SCHIZOSACCHAROMYCES-POMBE; CELL-INTEGRITY; SACCHAROMYCES-CEREVISIAE; CONTRACTILE-RING; SYNTHASE SUBUNIT; POLARIZED GROWTH; TURGOR PRESSURE AB Rho GAPs are important regulators of Rho GTPases, which are involved in various steps of cytokinesis and other processes. However, regulation of Rho-GAP cellular localization and function is not fully understood. Here we report the characterization of a novel coiled-coil protein Rng10 and its relationship with the Rho-GAP Rga7 in fission yeast. Both rng10 Delta and rga7 Delta result in defective septum and cell lysis during cytokinesis. Rng10 and Rga7 colocalize on the plasma membrane at the cell tips during interphase and at the division site during cell division. Rng10 physically interacts with Rga7 in affinity purification and coimmunoprecipitation. Of interest, Rga7 localization is nearly abolished without Rng10. Moreover, Rng10 and Rga7 work together to regulate the accumulation and dynamics of glucan synthases for successful septum formation in cytokinesis. Our results show that cellular localization and function of the Rho-GAP Rga7 are regulated by a novel protein, Rng10, during cytokinesis in fission yeast. C1 [Liu, Yajun; Lee, I-Ju; Lower, Casey A.; Wu, Jian-Qiu] Ohio State Univ, Davis Heart & Lung Res Inst, Dept Mol Genet, Columbus, OH 43210 USA. [Sun, Mingzhai; Ma, Jianjie] Ohio State Univ, Davis Heart & Lung Res Inst, Dept Surg, Columbus, OH 43210 USA. [Wu, Jian-Qiu] Ohio State Univ, Dept Biol Chem & Pharmacol, Columbus, OH 43210 USA. [Runge, Kurt W.] Cleveland Clin Lerner Coll Med, Dept Mol Genet, Cleveland, OH 44195 USA. [Lee, I-Ju] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. RP Wu, JQ (reprint author), Ohio State Univ, Davis Heart & Lung Res Inst, Dept Mol Genet, Columbus, OH 43210 USA.; Wu, JQ (reprint author), Ohio State Univ, Dept Biol Chem & Pharmacol, Columbus, OH 43210 USA. EM wu.620@osu.edu OI Runge, Kurt/0000-0001-8492-0530 FU National Institute of General Medical Sciences of the National Institutes of Health Grant [GM118746]; American Cancer Society Grant [RSG-13-005-01-CCG] FX We thank Mohan Balasubramanian, Takayoshi Kuno, Dannel McCollum, Stephen Osmani, Pilar Perez, Thomas Pollard, Juan Carlos Ribas, Shelley Sazer, and Ning Wang for strains and plasmids; the Anita Hopper, James Hopper, and Stephen Osmani laboratories, the Mass Spectrometry and Proteomics Facility at The Ohio State University, and Mary Morphew and Thomas Giddings, Jr., at the University of Colorado at Boulder for technical support; and members of the Wu laboratory for helpful discussions and suggestions. This work was supported by National Institute of General Medical Sciences of the National Institutes of Health Grant GM118746 and American Cancer Society Grant RSG-13-005-01-CCG to J.-Q.W. NR 86 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD AUG 15 PY 2016 VL 27 IS 16 BP 2528 EP 2541 DI 10.1091/mbc.E16-03-0156 PG 14 WC Cell Biology SC Cell Biology GA DU6OZ UT WOS:000382335800003 PM 27385337 ER PT J AU Otto, MW Kredlow, MA Smits, JAJ Hofmann, SG Tolin, DF de Kleine, RA van Minnen, A Evins, AE Pollack, MH AF Otto, Michael W. Kredlow, M. Alexandra Smits, Jasper A. J. Hofmann, Stefan G. Tolin, David F. de Kleine, Rianne A. van Minnen, Agnes Evins, A. Eden Pollack, Mark H. TI Enhancement of Psychosocial Treatment With D-Cycloserine: Models, Moderators, and Future Directions SO BIOLOGICAL PSYCHIATRY LA English DT Review DE Addiction; Anxiety; DCS; d-cycloserine; Depression; Extinction ID OBSESSIVE-COMPULSIVE DISORDER; COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; SOCIAL ANXIETY DISORDER; PLACEBO-CONTROLLED TRIAL; POSTTRAUMATIC-STRESS-DISORDER; FEAR-POTENTIATED STARTLE; D-ASPARTATE RECEPTOR; EXPOSURE THERAPY; RESPONSE PREVENTION AB Advances in the understanding of the neurobiology of fear extinction have resulted in the development of d-cycloserine (DCS), a partial glutamatergic N-methyl-D-aspartate agonist, as an augmentation strategy for exposure treatment. We review a decade of research that has focused on the efficacy of DCS for augmenting the mechanisms (e.g., fear extinction) and outcome of exposure treatment across the anxiety disorders. Following a series of small-scale studies offering strong support for this clinical application, more recent larger-scale studies have yielded mixed results, with some showing weak or no effects. We discuss possible explanations for the mixed findings, pointing to both patient and session (i.e., learning experiences) characteristics as possible moderators of efficacy, and offer directions for future research in this area. We also review recent studies that have aimed to extend the work on DCS augmentation of exposure therapy for the anxiety disorders to DCS enhancement of learning-based interventions for addiction, anorexia nervosa, schizophrenia, and depression. Here, we attend to both DCS effects on facilitating therapeutic outcomes and additional therapeutic mechanisms beyond fear extinction (e.g., appetitive extinction, hippocampal-dependent learning). C1 [Otto, Michael W.; Kredlow, M. Alexandra; Hofmann, Stefan G.] Boston Univ, Dept Psychol & Brain Sci, 648 Beacon St,Floor 6, Boston, MA 02215 USA. [Smits, Jasper A. J.] Univ Texas Austin, Mental Hlth Res Inst, Austin, TX 78712 USA. [Smits, Jasper A. J.] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA. [Tolin, David F.] Inst Living, Anxiety Disorders Ctr, Hartford, CT USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [de Kleine, Rianne A.; van Minnen, Agnes] Radboud Univ Nijmegen, Overwaal Ctr Anxiety Disorders, Pro Persona, Inst Behav Sci, Nijmegen, Netherlands. [Evins, A. Eden] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. [Pollack, Mark H.] Rush Univ, Med Ctr, Dept Psychiat, Chicago, IL 60612 USA. RP Otto, MW (reprint author), Boston Univ, Dept Psychol & Brain Sci, 648 Beacon St,Floor 6, Boston, MA 02215 USA. EM mwotto@bu.edu RI Hofmann, Stefan/B-8769-2014 OI Hofmann, Stefan/0000-0002-3548-9681 FU National Institutes of Health (NIH)/National Institute of Mental Health (NIMH) [R21MH102646]; NIH/NIMH [1F31MH103969, R34MH099318, R34MH086668, 5R34MH099309-02]; NIDA [K24 DA030443]; MicroTransponder Inc.; Concert Pharmaceuticals; ProPhase; Palo Alto Health Sciences, Inc.; Forum Pharmaceuticals; GlaxoSmithKline; Pfizer FX Dr. Otto's effort on this manuscript was supported by National Institutes of Health (NIH)/National Institute of Mental Health (NIMH) Grant No. R21MH102646. Ms. Kredlow's effort on this manuscript was supported by NIH/NIMH Grant No. 1F31MH103969. Dr. Smits' effort on this grant was supported by NIH/NIMH Grant No. R34MH099318. Dr. Hofmann's effort on this manuscript was supported by NIH/NIMH Grant No. R34MH086668. Dr. Evins' work on this manuscript was supported by NIDA Grant No. K24 DA030443. Dr. Pollack's effort on this manuscript was supported by NIH/NIMH Grant No. 5R34MH099309-02. The National Institutes of Health had no role in the writing of the report or in the decision to submit the manuscript for publication. The National Institutes of Health had no role other than financial support.; Dr. Otto reports serving, in the last 3 years, as a paid consultant for MicroTransponder Inc., Concert Pharmaceuticals, and ProPhase; providing expert consensus opinion for Otsuka Pharmaceuticals; receiving royalty support for use of the SIGH-A from ProPhase; and receiving book royalties from Oxford University Press, Routledge, and Springer. Dr. Hofmann reports serving on the Advisory Board of Palo Alto Health Sciences and Otsuka America Pharmaceutical, Inc. and receiving financial compensation for his participation as an advisor and receiving royalties from various book publishers and financial compensation for his editorial work from Springer Publications and the American Psychological Association. Dr. Tolin reports receiving research funding from Palo Alto Health Sciences, Inc. Dr. Evins has received grant support to her institution from Forum Pharmaceuticals (formerly Envivo pharmaceuticals), GlaxoSmithKline, and Pfizer. She has provided consultation on behalf of her institution to Reckitt Benckiser and Pfizer. Dr. Pollack reports serving on the advisory board or consulting for Clintara, Concert Pharmaceuticals, Corcept Therapeutics, Edgemont Pharmaceuticals, Eli Lilly, Ironwood Pharmaceuticals, Medavante, Merck, Palo Alto Health Sciences, and Project Plus; receiving equity from Doyen Medical, Medavante, Mensante Corporation, Mindsite, and Targia Pharmaceuticals; and receiving royalties/patents for SIGH-A and SAFER interviews. All other authors report no biomedical financial interests or potential conflicts of interest. NR 89 TC 2 Z9 2 U1 16 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD AUG 15 PY 2016 VL 80 IS 4 BP 274 EP 283 DI 10.1016/j.biopsych.2015.09.007 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA DS5QT UT WOS:000380838100009 PM 26520240 ER PT J AU Cooper, TM Cassar, J Eckroth, E Malvar, J Sposto, R Gaynon, P Chang, BH Gore, L August, K Pollard, JA DuBois, SG Silverman, LB Oesterheld, J Gammon, G Magoon, D Annesley, C Brown, PA AF Cooper, Todd M. Cassar, Jeannette Eckroth, Elena Malvar, Jemily Sposto, Richard Gaynon, Paul Chang, Bill H. Gore, Lia August, Keith Pollard, Jessica A. DuBois, Steven G. Silverman, Lewis B. Oesterheld, Javier Gammon, Guy Magoon, Daniel Annesley, Colleen Brown, Patrick A. TI A Phase I Study of Quizartinib Combined with Chemotherapy in Relapsed Childhood Leukemia: A Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) Study SO CLINICAL CANCER RESEARCH LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; INTERNAL TANDEM DUPLICATION; TYROSINE KINASE INHIBITOR; PROGNOSTIC-SIGNIFICANCE; FLT3 INHIBITORS; EXPRESSION; GENE; MLL; MUTATIONS AB Purpose: To determine a safe and biologically active dose of quizartinib (AC220), a potent and selective class III receptor tyrosine kinase (RTK) FLT3 inhibitor, in combination with salvage chemotherapy in children with relapsed acute leukemia. Experimental Design: Quizartinib was administered orally to children with relapsed AML or MLL-rearranged ALL following 5 days of high-dose cytarabine and etoposide (AE). A 3+3 dose escalation design was used to identify a safe and biologically active dose. Plasma inhibitory assay (PIA) testing was performed weekly to determine biologic activity. Results: Toxicities were consistent with intensive relapsed leukemia regimens. One of 6 patients experienced a dose-limiting toxicity (DLT) at 40 mg/m(2)/day (elevated lipase) and 1 of 9 had a DLT (hyperbilirubinemia) at the highest tested dose of 60 mg/m(2)/day. Of 17 response evaluable patients, 2 had complete response (CR), 1 complete response without platelet recovery (CRp), 1 complete response with incomplete neutrophil and platelet recovery (CRi), 10 stable disease (SD), and 3 progressive disease (PD). Of 7 FLT3-ITD patients, 1 achieved CR, 1 CRp, 1 Cri, and 4 SD. FLT3-ITD patients, but not FLT3 wild-type (WT) patients, had significantly lower blast counts post-quizartinib. FLT3 phosphorylation was completely inhibited in all patients. Conclusions: Quizartinib plus intensive chemotherapy is well tolerated at 60 mg/m(2)/day with near complete inhibition of FLT3 phosphorylation in all patients. The favorable toxicity profile, pharmacodynamic activity, and encouraging response rates warrant further testing of quizartinib in children with FLT3-ITD AML. (C) 2016 AACR. C1 [Cooper, Todd M.] Seattle Childrens Hosp, Canc & Blood Disorders Ctr, 4800 Sand Point Way NE,M-S MB8-501, Seattle, WA 98105 USA. [Cassar, Jeannette; Eckroth, Elena; Malvar, Jemily; Sposto, Richard; Gaynon, Paul] Childrens Hosp Los Angeles, Childrens Ctr Canc & Blood Dis, Los Angeles, CA 90027 USA. [Sposto, Richard; Gaynon, Paul] Univ Southern Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Chang, Bill H.] Oregon Hlth & Sci Univ, Doernbecher Childrens Hosp, Portland, OR 97201 USA. [Gore, Lia] Childrens Hosp Colorado, Aurora, CO USA. [August, Keith] Childrens Mercy Hosp & Clin, Kansas City, MO USA. [Pollard, Jessica A.] Maine Childrens Canc Program, Scarborough, ME USA. [DuBois, Steven G.; Silverman, Lewis B.] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA. [Oesterheld, Javier] Levine Childrens Hosp, Charlotte, NC USA. [Gammon, Guy] Ambit Biosci Corp, Clin Res & Dev, San Diego, CA USA. [Magoon, Daniel; Annesley, Colleen; Brown, Patrick A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Cooper, TM (reprint author), Seattle Childrens Hosp, Canc & Blood Disorders Ctr, 4800 Sand Point Way NE,M-S MB8-501, Seattle, WA 98105 USA. EM todd.cooper@seattlechildrens.org FU Phase One Foundation; TACL Consortium; Leukemia and Lymphoma Society (LLS Scholar in Clinical Research Grant) [2365-12]; American Cancer Society [120237] FX This work was financially supported by grants from the Phase One Foundation to Children's Hospital of Los Angeles, TACL Consortium. Quizartinib was provided by Ambit Biosciences Corporation. The correlative laboratory assays were funded by grants (to P. Brown) from the Leukemia and Lymphoma Society (LLS Scholar in Clinical Research Grant #2365-12) and the American Cancer Society (ACS Research Scholar Grant #120237). NR 26 TC 4 Z9 4 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 AUG 15 PY 2016 VL 22 IS 16 BP 4014 EP 4022 DI 10.1158/1078-0432.CCR-15-1998 PG 9 WC Oncology SC Oncology GA DU5QH UT WOS:000382265900006 PM 26920889 ER PT J AU Wu, SP Pfeiffer, RM Ahn, IE Mailankody, S Sonneveld, P van Duin, M Munshi, NC Walker, BA Morgan, G Landgren, O AF Wu, S. Peter Pfeiffer, Ruth M. Ahn, Inhye E. Mailankody, Sham Sonneveld, Pieter van Duin, Mark Munshi, Nikhil C. Walker, Brian A. Morgan, Gareth Landgren, Ola TI Impact of Genes Highly Correlated with MMSET Myeloma on the Survival of Non-MMSET Myeloma Patients SO CLINICAL CANCER RESEARCH LA English DT Article ID RISK MULTIPLE-MYELOMA; BREAST-CANCER RISK; T(4/14) MYELOMA; CELL-CYCLE; C-MYC; PLASMA-CELLS; EXPRESSION; PREDICTION; TRANSLOCATION; TRANSCRIPTS AB Purpose: The poor prognosis of multiple myeloma with t(4;14) is driven by the fusion of genes encoding multiple myeloma SET domain (MMSET) and immunoglobulin heavy chain. Specific genes affected by MMSET and their clinical implications in non-MMSET myeloma remain undetermined. Experimental Design: We obtained gene expression profiles of 1,032 newly diagnosed myeloma patients enrolled in Total Therapy 2, Total Therapy 3, Myeloma IX, and HOVON65-GMMGHD4 trials and 156 patients from Multiple Myeloma Resource Collection. Probes that correlated most with MMSET myeloma were selected on the basis of a multivariable linear regression and Bonferroni correction and refined on the basis of the strength of association with survival in non-MMSET patients. Results: Ten MMSET-like probes were associated with poor survival in non-MMSET myeloma. Non-MMSET myeloma patients in the highest quartile of the 10-gene signature (MMSET-like myeloma) had 5-year overall survival similar to that of MMSET myeloma [highest quartile vs. lowest quartile HR = 2.0; 95% confidence interval (CI), 1.5-2.8 in MMSET-like myeloma; HR = 2.3; 95% CI, 1.6-3.3 in MMSET myeloma]. Analyses of MMSET-like gene signature suggested the involvement of p53 and MYC pathways. Conclusions: MMSET-like gene signature captures a subset of high-risk myeloma patients underrepresented by conventional risk stratification platforms and defines a distinct biologic subtype. (C) 2016 AACR. C1 [Wu, S. Peter; Ahn, Inhye E.] NCI, Multiple Myeloma Sect, NIH, Bethesda, MD 20892 USA. [Pfeiffer, Ruth M.] NCI, Dept Canc Epidemiol & Genet, Biostat Branch, NIH, Rockville, MD USA. [Mailankody, Sham; Landgren, Ola] Mem Sloan Kettering Canc Ctr, Myeloma Serv, New York, NY 10021 USA. [Sonneveld, Pieter; van Duin, Mark] Erasmus Univ, Med Ctr, Dept Hematol, Rotterdam, Netherlands. [Munshi, Nikhil C.] Harvard Med Sch, Lebow Inst Myeloma Therapeut, Boston, MA USA. [Munshi, Nikhil C.] Harvard Med Sch, Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, Boston, MA USA. [Walker, Brian A.] Inst Canc Res, Sect Haematooncol, London, England. [Morgan, Gareth] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. RP Landgren, O (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA. EM landgrec@mskcc.org OI Walker, Brian/0000-0002-8615-6254 FU NIH; NIH Medical Research Scholars Program FX This work was supported by the intramural research program of the NIH. Research support for S.P. Wu was made possible through the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from Pfizer Inc., The Leona M. and Harry B. Helmsley Charitable Trust, and the Howard Hughes Medical Institute, as well as other private donors. For a complete list, please visit the Foundation website at http://www.fnih.org/work/programs-development/medical-research-scholars- program. NR 35 TC 1 Z9 1 U1 0 U2 0 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 AUG 15 PY 2016 VL 22 IS 16 BP 4039 EP 4044 DI 10.1158/1078-0432.CCR-15-2366 PG 6 WC Oncology SC Oncology GA DU5QH UT WOS:000382265900009 PM 26847058 ER PT J AU Tang, M Zhao, R de Velde, HV Tross, JG Mitsiades, C Viselli, S Neuwirth, R Esseltine, DL Anderson, K Ghobrial, IM San Miguel, JF Richardson, PG Tomasson, MH Michor, F AF Tang, Min Zhao, Rui de Velde, Helgi van Tross, Jennifer G. Mitsiades, Constantine Viselli, Suzanne Neuwirth, Rachel Esseltine, Dixie-Lee Anderson, Kenneth Ghobrial, Irene M. San Miguel, Jesus F. Richardson, Paul G. Tomasson, Michael H. Michor, Franziska TI Myeloma Cell Dynamics in Response to Treatment Supports a Model of Hierarchical Differentiation and Clonal Evolution SO CLINICAL CANCER RESEARCH LA English DT Article ID RELAPSED MULTIPLE-MYELOMA; BORTEZOMIB-MELPHALAN-PREDNISONE; DRUG-RESISTANCE; STAGING SYSTEM; TUMOR-GROWTH; FOLLOW-UP; DEXAMETHASONE; CHEMOTHERAPY; MALIGNANCIES; PROGENITORS AB Purpose: Since the pioneering work of Salmon and Durie, quantitative measures of tumor burden in multiple myeloma have been used to make clinical predictions and model tumor growth. However, such quantitative analyses have not yet been performed on large datasets from trials using modern chemotherapy regimens. Experimental Design: We analyzed a large set of tumor response data from three randomized controlled trials of bortezomib-based chemotherapy regimens (total sample size n = 1,469 patients) to establish and validate a novel mathematical model of multiple myeloma cell dynamics. Results: Treatment dynamics in newly diagnosed patients were most consistent with a model postulating two tumor cell subpopulations, "progenitor cells" and "differentiated cells." Differential treatment responses were observed with significant tumoricidal effects on differentiated cells and less clear effects on progenitor cells. We validated this model using a second trial of newly diagnosed patients and a third trial of refractory patients. When applying our model to data of relapsed patients, we found that a hybrid model incorporating both a differentiation hierarchy and clonal evolution best explains the response patterns. Conclusions: The clinical data, together with mathematical modeling, suggest that bortezomib-based therapy exerts a selection pressure on myeloma cells that can shape the disease phenotype, thereby generating further inter-patient variability. This model may be a useful tool for improving our understanding of disease biology and the response to chemotherapy regimens. 14. (C) 2016 AACR. C1 [Tang, Min; Zhao, Rui; Tross, Jennifer G.; Michor, Franziska] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Tang, Min; Zhao, Rui; Michor, Franziska] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [de Velde, Helgi van; Neuwirth, Rachel; Esseltine, Dixie-Lee] Takeda Pharmaceut Inc, Cambridge, MA USA. [Tross, Jennifer G.] Harvard Med Sch, Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. [Mitsiades, Constantine; Anderson, Kenneth; Ghobrial, Irene M.; Richardson, Paul G.] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. [Viselli, Suzanne] Janssen Res & Dev LLC, Oncol R&D, Raritan, NJ USA. [San Miguel, Jesus F.] USAL, CSIC, IBMCC, Hosp Univ Salamanca,CIC, Salamanca, Spain. [Tomasson, Michael H.] Washington Univ, Sch Med, Div Oncol, St Louis, MO USA. RP Michor, F (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM michor@jimmy.harvard.edu FU Dana-Farber Cancer Institute Physical Sciences-Oncology Center [U54CA193461] FX The authors thank the Michor lab, Mithat Gonen, Katherine Weilbaecher, Rameen Beroukhim, Victor DeGruttola, and Paul Catalano for helpful discussions, especially thank all the participating patients, their families, the research teams and the clinical investigators in the VISTA, MMY-2001, and APEX studies, and acknowledge the support from the Dana-Farber Cancer Institute Physical Sciences-Oncology Center (U54CA193461). NR 33 TC 1 Z9 1 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 AUG 15 PY 2016 VL 22 IS 16 BP 4206 EP 4214 DI 10.1158/1078-0432.CCR-15-2793 PG 9 WC Oncology SC Oncology GA DU5QH UT WOS:000382265900024 PM 27006493 ER PT J AU Huang, YS Nahar, S Nakagawa, A Fernandez-Barrena, MG Mertz, JA Bryant, BM Adams, CE Mino-Kenudson, M Von Alt, KN Chang, K Conery, AR Hatton, C Sims, RJ Fernandez-Zapico, ME Wang, XP Lillemoe, KD Fernandez-del Castillo, C Warshaw, AL Thayer, SP Liss, AS AF Huang, Yinshi Nahar, Sabikun Nakagawa, Akifumi Fernandez-Barrena, Maite G. Mertz, Jennifer A. Bryant, Barbara M. Adams, Curtis E. Mino-Kenudson, Mari Von Alt, Kate N. Chang, Kevin Conery, Andrew R. Hatton, Charlie Sims, Robert J., III Fernandez-Zapico, Martin E. Wang, Xingpeng Lillemoe, Keith D. Fernandez-del Castillo, Carlos Warshaw, Andrew L. Thayer, Sarah P. Liss, Andrew S. TI Regulation of GLI Underlies a Role for BET Bromodomains in Pancreatic Cancer Growth and the Tumor Microenvironment SO CLINICAL CANCER RESEARCH LA English DT Article ID PROSTATE-CANCER; ONCOGENIC KRAS; MOUSE MODEL; INHIBITION; HEDGEHOG; PROGRESSION; PATHWAY; TARGET; BRD4; MYC AB Purpose: The initiation, progression, and maintenance of pancreatic ductal adenocarcinoma (PDAC) results from the interplay of genetic and epigenetic events. While the genetic alterations of PDAC have been well characterized, epigenetic pathways regulating PDAC remain, for the most part, elusive. The goal of this study was to identify novel epigenetic regulators contributing to the biology of PDAC. Experimental Design: In vivo pooled shRNA screens targeting 118 epigenetic proteins were performed in two orthotopic PDAC xenograft models. Candidate genes were characterized in 19 human PDAC cell lines, heterotopic xenograft tumor models, and a genetically engineered mouse (GEM) model of PDAC. Gene expression, IHC, and immunoprecipitation experiments were performed to analyze the pathways by which candidate genes contribute to PDAC. Results: In vivo shRNA screens identified BRD2 and BRD3, members of the BET family of chromatin adaptors, as key regulators of PDAC tumor growth. Pharmacologic inhibition of BET bromodomains enhanced survival in a PDAC GEM model and inhibited growth of hum an-derived xenograft tumors. BET proteins contribute to PDAC cell growth through direct interaction with members of the GLI family of transcription factors and modulating their activity. Within cancer cells, BET bromodomain inhibition results in down regulation of SHH, a key mediator of the tumor microenvironrnent and canonical activator of GLI. Consistent with this, inhibition of BET bromodomains decreases cancer-associated fibroblast content of tumors in both GEM and xenograft tumor models. Conclusions: Therapeutic inhibition of BET proteins offers a novel mechanism to target both the neoplastic and stromal components of PDAC. (C) 2016 AACR. C1 [Huang, Yinshi; Wang, Xingpeng] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Gastroenterol, Shanghai, Peoples R China. [Huang, Yinshi; Nahar, Sabikun; Nakagawa, Akifumi; Adams, Curtis E.; Von Alt, Kate N.; Chang, Kevin; Lillemoe, Keith D.; Fernandez-del Castillo, Carlos; Warshaw, Andrew L.; Thayer, Sarah P.; Liss, Andrew S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Huang, Yinshi; Nahar, Sabikun; Nakagawa, Akifumi; Adams, Curtis E.; Von Alt, Kate N.; Chang, Kevin; Lillemoe, Keith D.; Fernandez-del Castillo, Carlos; Warshaw, Andrew L.; Thayer, Sarah P.; Liss, Andrew S.] Massachusetts Gen Hosp, Andrew L Warshaw MD Inst Pancreat Canc Res, Boston, MA 02114 USA. [Huang, Yinshi; Nahar, Sabikun; Nakagawa, Akifumi; Adams, Curtis E.; Mino-Kenudson, Mari; Von Alt, Kate N.; Chang, Kevin; Lillemoe, Keith D.; Fernandez-del Castillo, Carlos; Warshaw, Andrew L.; Thayer, Sarah P.; Liss, Andrew S.] Harvard Med Sch, Boston, MA USA. [Fernandez-Barrena, Maite G.; Fernandez-Zapico, Martin E.] Mayo Clin, Schulze Ctr Novel Therapeut, Div Oncol Res, Rochester, MN USA. [Mertz, Jennifer A.; Bryant, Barbara M.; Conery, Andrew R.; Hatton, Charlie; Sims, Robert J., III] Constellat Pharmaceut, Cambridge, MA USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Wang, Xingpeng] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 1, Dept Gastroenterol, Shanghai, Peoples R China. RP Liss, AS (reprint author), Massachusetts Gen Hosp, 55 Blossom St,Thier 623, Boston, MA 02114 USA.; Thayer, SP (reprint author), Univ Nebraska Med Ctr, 986345 Nebraska Med Ctr, Omaha, NE 68198 USA. EM sarah.thayer@unmc.edu; aliss@mgh.harvard.edu FU Institute for Pancreatic Cancer Research; NIH [P01CA117969] FX This work was supported by a grant from The Andrew L. Warshaw, MD Institute for Pancreatic Cancer Research (awarded to A.S. Liss) and a grant from the NIH(P01CA117969; awarded to S.P. Thayer). NR 43 TC 1 Z9 1 U1 4 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 15 PY 2016 VL 22 IS 16 BP 4259 EP 4270 DI 10.1158/1078-0432.CCR-15-2068 PG 12 WC Oncology SC Oncology GA DU5QH UT WOS:000382265900029 PM 27169995 ER PT J AU Uribe-Patarroyo, N Bouma, BE AF Uribe-Patarroyo, Nestor Bouma, Brett E. TI Velocity gradients in spatially resolved laser Doppler flowmetry and dynamic light scattering with confocal and coherence gating SO PHYSICAL REVIEW E LA English DT Article ID SPECKLE DECORRELATION; FLOW-VELOCITY; TOMOGRAPHY; RESOLUTION; SPECTRUM; SPEED AB Dynamic light scattering (DLS) is widely used to characterize diffusive motion to obtain precise information on colloidal suspensions by calculating the autocorrelation function of the signal from a heterodyne optical system. DLS can also be used to determine the flow velocity field in systems that exhibit mass transport by incorporating the effects of the deterministic motion of scatterers on the autocorrelation function, a technique commonly known as laser Doppler flowmetry. DLS measurements can be localized with confocal and coherence gating techniques such as confocal microscopy and optical coherence tomography, thereby enabling the determination of the spatially resolved velocity field in three dimensions. It has been thought that spatially resolved DLS can determine the axial velocity as well as the lateral speed in a single measurement. We demonstrate, however, that gradients in the axial velocity of scatterers exert a fundamental influence on the autocorrelation function even in well-behaved, nonturbulent flow. By obtaining the explicit functional relation between axial-velocity gradients and the autocorrelation function, we show that the velocity field and its derivatives are intimately related and their contributions cannot be separated. Therefore, a single DLS measurement cannot univocally determine the velocity field. Our extended theoretical model was found to be in good agreement with experimental measurements. C1 [Uribe-Patarroyo, Nestor; Bouma, Brett E.] Harvard Med Sch, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. [Uribe-Patarroyo, Nestor; Bouma, Brett E.] Massachusetts Gen Hosp, 40 Blossom St, Boston, MA 02114 USA. RP Uribe-Patarroyo, N (reprint author), Harvard Med Sch, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA.; Uribe-Patarroyo, N (reprint author), Massachusetts Gen Hosp, 40 Blossom St, Boston, MA 02114 USA. EM uribepatarroyo.nestor@mgh.harvard.edu FU National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health [P41 EB015903]; Terumo Corporation FX Research in this publication was supported in part by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health, Grant No. P41 EB015903, and by Terumo Corporation. NR 31 TC 0 Z9 0 U1 9 U2 9 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 2470-0045 EI 2470-0053 J9 PHYS REV E JI Phys. Rev. E PD AUG 15 PY 2016 VL 94 IS 2 AR 022604 DI 10.1103/PhysRevE.94.022604 PG 11 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA DT5AF UT WOS:000381492200011 PM 27627357 ER PT J AU Mowafy, S Galanis, A Doctor, ZM Paranal, RM Lasheen, DS Farag, NA Janne, PA Abouzid, KAM AF Mowafy, Samar Galanis, A. Doctor, Zainab M. Paranal, Raymond M. Lasheen, Deena S. Farag, Nahla A. Janne, Pasi A. Abouzid, Khaled A. M. TI Toward discovery of mutant EGFR inhibitors; Design, synthesis and in vitro biological evaluation of potent 4-arylamino-6-ureido and thioureido-quinazoline derivatives SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE EGFR inhibitors; Quinazolines; Urea derivatives; Synthesis; EGFR-Her2 dual inhibitors; EGFR L858R/T790 mutant; EGFR Del19/T790M mutant ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITORS; LUNG-CANCER; CELL-LINES; RESISTANCE; MUTATION; 4-ANILINOQUINAZOLINES; AMPLIFICATION; MECHANISM AB A new series of w4-anilinoquinazolines with C-6 ureido and thioureido side chains and various sub-stituents at the C-4 anilino moiety was designed, synthesized and evaluated as wild type (WT) and mutant EGFR inhibitors. Most of the compounds inhibited EGFR kinase wild type (EGFR WT) with IC50 values in the low nanomolar range (<0.495-9.05 nM) and displayed more potent cytotoxic effect in BaF/3 expressing EGFR WT than reference compound gefitinib. The anti-proliferative effect of all synthesized compounds against gefitinib insensitive double mutant cell lines Ba/F3 expressing Del19/T790M and Ba/F3 expressing L858R/T790M were assayed. Compounds 4d, 6f, 7e showed significant inhibition (IC50 = 1.76-2.38 mu M) in these mutant lines and significant Her2 enzyme inhibition (IC50 = 19.2-40.6 nM) compared to lapatinib (60.1 nM). The Binding mode of compounds 6d, 6f, 7a, 7b and 8b were demonstrated. Furthermore, growth inhibition against gefitinib insensitive cell lines PC9-GR4 (Del19/T790M) were tested, compounds 6f and 7e showed about eight and three folds respectively greater potency than gefitinib. Our structure-activity relationships (SAR) studies suggested that presence of ethyl piperidino urea/thiourea at 6-position and bulky group of (3-chloro-4-(3-fluorobenzyloxy) phenyl) amino at 4-position of quinazoline may serve as promising scaffold for developing inhibitors against wild type and mutant EGFR. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Mowafy, Samar; Doctor, Zainab M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Mowafy, Samar; Doctor, Zainab M.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, 250 Longwood Ave,SGM 628, Boston, MA 02115 USA. [Mowafy, Samar; Farag, Nahla A.] Misr Int Univ, Fac Pharm, Dept Pharmaceut Chem, Km 28 Cairo Ismailia Rd, Cairo, Egypt. [Galanis, A.; Paranal, Raymond M.; Janne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Lasheen, Deena S.; Abouzid, Khaled A. M.] Ain Shams Univ, Fac Pharm, Dept Pharmaceut Chem, Cairo 11566, Egypt. RP Mowafy, S (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.; Mowafy, S (reprint author), Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, 250 Longwood Ave,SGM 628, Boston, MA 02115 USA.; Mowafy, S (reprint author), Misr Int Univ, Fac Pharm, Dept Pharmaceut Chem, Km 28 Cairo Ismailia Rd, Cairo, Egypt.; Abouzid, KAM (reprint author), Ain Shams Univ, Fac Pharm, Dept Pharmaceut Chem, Cairo 11566, Egypt. EM samarmowafy@gmail.com; khaled.abouzid@pharma.asu.edu.eg FU Fulbright commission FX I am grateful to the Fulbright commission for the scholarship opportunity, Professor Nathanael Gray for his continuous support and Dr Jaebong Jang in Gray lab for providing guidance and help during this research. I would like to thank Dr Ciric in Pasi lab for sharing thoughts on running double mutant cell line experiments. NR 22 TC 0 Z9 0 U1 8 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 EI 1464-3391 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD AUG 15 PY 2016 VL 24 IS 16 BP 3501 EP 3512 DI 10.1016/j.bmc.2016.05.063 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA DS2AF UT WOS:000380515700019 PM 27288180 ER PT J AU Rynearson, KD Buckle, RN Barnes, KD Herr, RJ Mayhew, NJ Paquette, WD Sakwa, SA Nguyen, PD Johnson, G Tanzi, RE Wagner, SL AF Rynearson, Kevin D. Buckle, Ronald N. Barnes, Keith D. Herr, R. Jason Mayhew, Nicholas J. Paquette, William D. Sakwa, Samuel A. Nguyen, Phuong D. Johnson, Graham Tanzi, Rudolph E. Wagner, Steven L. TI Design and synthesis of aminothiazole modulators of the gamma-secretase enzyme SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Alzheimer's disease; gamma-Secretase modulators; Aminothiazoles ID ALZHEIMERS-DISEASE; AMYLOID HYPOTHESIS; THERAPEUTIC TARGET; SENILE PLAQUES; MOUSE MODEL; DISCOVERY; PROGRESS; PROTEIN; PERSPECTIVE; INHIBITORS AB The design and construction of a series of novel aminothiazole-derived gamma-secretase modulators is described. The incorporation of heterocyclic replacements of the terminal phenyl D-ring of lead compound 1 was conducted in order to align potency with favorable drug-like properties. gamma-Secretase modulator 28 displayed good activity for in vitro inhibition of A beta 42, as well as substantial improvement in ADME and physicochemical properties, including aqueous solubility. Pharmacokinetic evaluation of compound 28 in mice revealed good brain penetration, as well as good clearance, half-life, and volume of distribution which collectively support the continued development of this class of compounds. (C) 2016 Published by Elsevier Ltd. C1 [Rynearson, Kevin D.; Nguyen, Phuong D.; Wagner, Steven L.] Univ Calif San Diego, Dept Neurosci, 9500 Gilman Dr MC 0624, La Jolla, CA 92093 USA. [Buckle, Ronald N.; Barnes, Keith D.; Herr, R. Jason; Mayhew, Nicholas J.; Paquette, William D.; Sakwa, Samuel A.] AMRI, Dept Med Chem, East Campus,3 Univ Pl, Rensselaer, NY 12144 USA. [Johnson, Graham] NuPharmAdvise, 3 Lakeside Dr, Sanbornton, NH 03269 USA. [Tanzi, Rudolph E.] Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, Charlestown, MA 02129 USA. RP Wagner, SL (reprint author), Univ Calif San Diego, Dept Neurosci, 9500 Gilman Dr MC 0624, La Jolla, CA 92093 USA. EM slwagner@ucsd.edu NR 44 TC 0 Z9 0 U1 5 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X EI 1464-3405 J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD AUG 15 PY 2016 VL 26 IS 16 BP 3928 EP 3937 DI 10.1016/j.bmcl.2016.07.011 PG 10 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA DS2FB UT WOS:000380574400018 PM 27426299 ER PT J AU Wang, X Beste, LA Maier, MM Zhou, XH AF Wang, Xuan Beste, Lauren A. Maier, Marissa M. Zhou, Xiao-Hua TI Double robust estimator of average causal treatment effect for censored medical cost data SO STATISTICS IN MEDICINE LA English DT Article DE average causal treatment effect; censored data; double robust estimator; inverse probability weighted; lifetime medical cost data ID DEPENDENT TERMINAL EVENT; PROPENSITY SCORE; LONGITUDINAL DATA; REGRESSION; TIMES; MODEL AB In observational studies, estimation of average causal treatment effect on a patient's response should adjust for confounders that are associated with both treatment exposure and response. In addition, the response, such as medical cost, may have incomplete follow-up. In this article, a double robust estimator is proposed for average causal treatment effect for right censored medical cost data. The estimator is double robust in the sense that it remains consistent when either the model for the treatment assignment or the regression model for the response is correctly specified. Double robust estimators increase the likelihood the results will represent a valid inference. Asymptotic normality is obtained for the proposed estimator, and an estimator for the asymptotic variance is also derived. Simulation studies show good finite sample performance of the proposed estimator and a real data analysis using the proposed method is provided as illustration. Copyright (c) 2016 John Wiley & Sons, Ltd. C1 [Wang, Xuan; Zhou, Xiao-Hua] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Beste, Lauren A.] Univ Washington, VA Puget Sound Hlth Care Syst, Div Gen Internal Med, VA Natl Liver Dis Database,Sch Med, Seattle, WA USA. [Maier, Marissa M.] Oregon Hlth & Sci Univ, HIV Hepatitis & Publ Hlth Pathogens Program, VA Portland Hlth Care Syst,Div Infect Dis, Infect Dis Sect,Off Patient Care Serv,VHA, Portland, OR 97201 USA. [Zhou, Xiao-Hua] Seattle HSR Ctr Innovat Veteran Cr & Value Driven, Dept Vet Affairs Med Ctr, Seattle, WA USA. RP Zhou, XH (reprint author), Univ Washington, Dept Biostat, Seattle, WA 98195 USA. EM azhou@u.washington.edu FU US Department of Veterans Affairs, Veterans Affairs Health Administration Research Career Scientist Award [RCS 05-196] FX Xiao-Hua (Andrew) Zhou, PhD, is presently the Core Investigator and Biostatistics Unit Director at the Seattle HSR&D Center of Innovation for Veteran-Centered and Value-Driven Care, Department of Veterans Affairs Medical Center, Seattle, WA. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. Dr. Zhou's work was supported in part by US Department of Veterans Affairs, Veterans Affairs Health Administration Research Career Scientist Award (RCS 05-196), NR 23 TC 0 Z9 0 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD AUG 15 PY 2016 VL 35 IS 18 BP 3101 EP 3116 DI 10.1002/sim.6876 PG 16 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA DR6PZ UT WOS:000380025100005 PM 26818601 ER PT J AU Lee, D Ganna, A Pawitan, Y Lee, W AF Lee, Donghwan Ganna, Andrea Pawitan, Yudi Lee, Woojoo TI Nonparametric estimation of the rediscovery rate SO STATISTICS IN MEDICINE LA English DT Article DE rediscovery rate; multiple testing; false discovery rate; validation study ID GENOME-WIDE ASSOCIATION AB Validation studies have been used to increase the reliability of the statistical conclusions for scientific discoveries; such studies improve the reproducibility of the findings and reduce the possibility of false positives. Here, one of the important roles of statistics is to quantify reproducibility rigorously. Two concepts were recently defined for this purpose: (i) rediscovery rate (RDR), which is the expected proportion of statistically significant findings in a study that can be replicated in the validation study and (ii) false discovery rate in the validation study (vFDR). In this paper, we aim to develop a nonparametric approach to estimate the RDR and vFDR and show an explicit link between the RDR and the FDR. Among other things, the link explains why reproducing statistically significant results even with low FDR level may be difficult. Two metabolomics datasets are considered to illustrate the application of the RDR and vFDR concepts in high-throughput data analysis. Copyright (c) 2016 John Wiley & Sons, Ltd. C1 [Lee, Donghwan] Ewha Womans Univ, Dept Stat, Seoul, South Korea. [Ganna, Andrea; Pawitan, Yudi] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Ganna, Andrea] Broad Inst & MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Ganna, Andrea] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Ganna, Andrea] Harvard Med Sch, Boston, MA USA. [Lee, Woojoo] Inha Univ, Dept Stat, Inchon, South Korea. RP Lee, W (reprint author), Inha Univ, Dept Stat, Inchon, South Korea. EM lwj221@gmail.com OI Ganna, Andrea/0000-0002-8147-240X FU Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICTFuture Planning [NRF-2013R1A1A1061332]; Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning [NRF-2015R1C1A1A01055524]; Ewha Womans University Research Grant FX Woojoo Lee was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT&Future Planning (NRF-2013R1A1A1061332). Donghwan Leewas supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2015R1C1A1A01055524) and also supported by the 2014 Ewha Womans University Research Grant. 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 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD AUG 15 PY 2016 VL 35 IS 18 BP 3203 EP 3212 DI 10.1002/sim.6915 PG 10 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA DR6PZ UT WOS:000380025100012 PM 26910365 ER PT J AU Hanyuda, A Ogino, S Qian, ZR Nishihara, R Song, MY Mima, K Inamura, K Masugi, Y Wu, KN Meyerhardt, JA Chan, AT Fuchs, CS Giovannucci, EL Cao, Y AF Hanyuda, Akiko Ogino, Shuji Qian, Zhi Rong Nishihara, Reiko Song, Mingyang Mima, Kosuke Inamura, Kentaro Masugi, Yohei Wu, Kana Meyerhardt, Jeffrey A. Chan, Andrew T. Fuchs, Charles S. Giovannucci, Edward L. Cao, Yin TI Body mass index and risk of colorectal cancer according to tumor lymphocytic infiltrate SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE body mass index; colorectal carcinoma; lymphocytic reaction; molecular pathological epidemiology ID MOLECULAR PATHOLOGICAL EPIDEMIOLOGY; ISLAND METHYLATOR PHENOTYPE; C-REACTIVE PROTEIN; MICROSATELLITE INSTABILITY; LIFE-STYLE; COLON-CANCER; DISEASE; OBESITY; FEATURES; ASSOCIATIONS AB Higher body mass index (BMI), higher body adiposity and obesity have been associated with increased risk of colorectal cancer. Evidence suggests that excess energy balance may influence systemic immune and inflammatory status. Thus, we hypothesized that the positive association between BMI and colorectal cancer risk might differ according to colorectal carcinoma subtypes according to levels of histopathological lymphocytic reaction to tumor. We collected biennial questionnaire data on weight and baseline height information in two prospective cohort studies, the Nurses' Health Study (1980-2010) and the Health Professionals Follow-up Study (1986-2010). Utilizing duplication-method Cox proportional hazards regression models, we prospectively assessed the association between BMI and risk of colorectal cancer subtypes according to the degree of Crohn's-like lymphoid reaction, peritumoral lymphocytic reaction, intratumoral periglandular reaction, tumor-infiltrating lymphocytes, the overall lymphocytic reaction score, or T-cell [CD3(+), CD8(+), CD45RO (PTPRC)(+) or FOXP3(+)] density in tumor tissue. Statistical significance level was adjusted for multiple hypotheses testing by Bonferroni correction. During follow up of 1,708,029 men and women (over 3,346,752 person-years), we documented 1,436 incident rectal and colon cancer cases with available formalin-fixed paraffin-embedded tumor tissue materials and pathological immunity data. BMI was significantly associated with higher risk of overall colorectal cancer (P-trend < 0.001); however, the association of BMI with colorectal carcinoma risk did not significantly differ by the level of lymphocytic reaction or T-cell infiltration in tumor tissue status (P-heterogeneity > 0.10). BMI may be associated with risk of colorectal cancer regardless of levels of lymphocytic response to tumor. C1 [Hanyuda, Akiko; Nishihara, Reiko; Song, Mingyang; Wu, Kana; Giovannucci, Edward L.; Cao, Yin] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Div MPE Mol Pathol Epidemiol, 75 Francis St, Boston, MA 02115 USA. [Ogino, Shuji; Qian, Zhi Rong; Nishihara, Reiko; Song, Mingyang; Mima, Kosuke; Inamura, Kentaro; Masugi, Yohei; Meyerhardt, Jeffrey A.; Chan, Andrew T.; Fuchs, Charles S.; Giovannucci, Edward L.; Cao, Yin] Harvard Univ, Sch Med, Boston, MA USA. [Ogino, Shuji; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Ogino, Shuji; Qian, Zhi Rong; Nishihara, Reiko; Song, Mingyang; Mima, Kosuke; Inamura, Kentaro; Masugi, Yohei; Meyerhardt, Jeffrey A.; Chan, Andrew T.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ogino, Shuji; Nishihara, Reiko; Giovannucci, Edward L.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Nishihara, Reiko] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Song, Mingyang; Chan, Andrew T.; Cao, Yin] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Song, Mingyang; Chan, Andrew T.; Cao, Yin] Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, 55 Fruit St, Boston, MA 02115 USA. [Inamura, Kentaro] JFCR, Inst Canc, Div Pathol, Tokyo, Japan. [Chan, Andrew T.; Fuchs, Charles S.; Giovannucci, Edward L.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. RP Cao, Y (reprint author), Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, 55 Fruit St, Boston, MA 02115 USA.; Giovannucci, EL (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Nutr & Epidemiol, 655 Huntington Ave, Boston, MA 02215 USA. EM egiovann@hsph.harvard.edu; yic576@mail.harvard.edu FU U.S. National Institutes of Health (NIH) [K07 CA190673, R01 CA137178, K24 DK098311, P50 CA127003, R01 CA151993, R35 CA197735, UM1 CA186107, P01 CA87969, P01 CA55075, UM1 CA167552]; Project P Fund, the Friends of the Dana-Farber Cancer Institute; Bennett Family Fund; Entertainment Industry Foundation through National Colorectal Cancer Research Alliance; Japan-United States Educational Exchange Promotion Foundation (Fulbright Foundation), Japan; Japan Society for the Promotion of Science Postdoctoral Fellowship for Research Abroad; Takashi Tsuruo Memorial Fund, Japan; Program for Advancing Strategic International Networks to Accelerate the Circulation of Talented Researchers from Japanese Society for the Promotion of Science; Keio Gijuku Fukuzawa Memorial Fund for the Advancement of Education and Research FX Grant sponsor: U.S. National Institutes of Health (NIH); Grant number: K07 CA190673, R01 CA137178, K24 DK098311, P50 CA127003, R01 CA151993, R35 CA197735, UM1 CA186107, P01 CA87969, P01 CA55075, UM1 CA167552; Grant sponsors: Project P Fund, the Friends of the Dana-Farber Cancer Institute, the Bennett Family Fund and the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance. Japan-United States Educational Exchange Promotion Foundation (Fulbright Foundation), Japan; Japan Society for the Promotion of Science Postdoctoral Fellowship for Research Abroad, Takashi Tsuruo Memorial Fund, Japan, Program for Advancing Strategic International Networks to Accelerate the Circulation of Talented Researchers from Japanese Society for the Promotion of Science, Keio Gijuku Fukuzawa Memorial Fund for the Advancement of Education and Research NR 50 TC 4 Z9 4 U1 3 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD AUG 15 PY 2016 VL 139 IS 4 BP 854 EP 868 DI 10.1002/ijc.30122 PG 15 WC Oncology SC Oncology GA DP3TM UT WOS:000378418300021 PM 27037951 ER PT J AU Yu, YJ Wu, TB Johnson-Buck, A Li, LD Su, X AF Yu, Yingjie Wu, Tongbo Johnson-Buck, Alexander Li, Lidan Su, Xin TI A two-layer assay for single-nucleotide variants utilizing strand displacement and selective digestion SO BIOSENSORS & BIOELECTRONICS LA English DT Article DE Single nucleotide variant; Toehold strand displacement; Lambda exonuclease; Fluorescent probe ID DNA; HYBRIDIZATION; MUTATIONS; MEDICINE; PLASMA AB Point mutations have emerged as prominent biomarkers for disease diagnosis, particularly in the case of cancer. Discovering single-nucleotide variants (SNVs) is also of great importance for the identification of single-nucleotide polymorphisms within the population. The competing requirements of thermodynamic stability and specificity in conventional nucleic acid hybridization probes make it challenging to achieve highly precise detection of point mutants. Here, we present a fluorescence-based assay for low abundance mutation detection based on toehold-mediated strand displacement and nuclease-mediated strand digestion that enables highly precise detection of point mutations. We demonstrate that this combined assay provides 50-1000-fold discrimination (mean value: 255) between all possible single nucleotide mutations and their corresponding wild-type sequence for a model DNA target. Using experiments and kinetic modeling, we investigate probe properties that obtain additive benefits from both strand displacement and nucleolytic digestion, thus providing guidance for the design of enzyme mediated nucleic acid assays in the future. (C) 2016 Elsevier B.V. All rights reserved. C1 [Yu, Yingjie; Li, Lidan; Su, Xin] Beijing Univ Chem Technol, Coll Life Sci & Technol, Beijing 100029, Peoples R China. [Yu, Yingjie] SUNY Stony Brook, Mat Sci & Engn, Stony Brook, NY 11790 USA. [Wu, Tongbo] Peking Univ, Beijing Natl Lab Mol Sci, Coll Chem & Mol Engn, MOE Key Lab Bioorgan Chem & Mol Engn, Beijing 100871, Peoples R China. [Johnson-Buck, Alexander] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. RP Su, X (reprint author), 15 North Third Ring Rd, Beijing 100029, Peoples R China. EM xinsu@mail.buct.edu.cn FU National Natural Science Foundation of China [81273631]; subject promotion plan of Beijing University of Chemical Technology [ys12060026025] FX We thank Prof. Meiping Zhao at Peking University for her kindly providing instruments. This work was supported by the National Natural Science Foundation of China (81273631) and subject promotion plan of Beijing University of Chemical Technology (ys12060026025). NR 18 TC 0 Z9 0 U1 10 U2 39 PU ELSEVIER ADVANCED TECHNOLOGY PI OXFORD PA OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-5663 EI 1873-4235 J9 BIOSENS BIOELECTRON JI Biosens. Bioelectron. PD AUG 15 PY 2016 VL 82 BP 248 EP 254 DI 10.1016/j.bios.2016.03.070 PG 7 WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical; Electrochemistry; Nanoscience & Nanotechnology SC Biophysics; Biotechnology & Applied Microbiology; Chemistry; Electrochemistry; Science & Technology - Other Topics GA DM7MT UT WOS:000376545400036 ER PT J AU Murias, G Montanya, J Chacon, E Estruga, A Subira, C Fernandez, R Sales, B de Haro, C Lopez-Aguilar, J Lucangelo, U Villar, J Kacmarek, RM Blanch, L AF Murias, Gaston Montanya, Jaume Chacon, Encarna Estruga, Anna Subira, Carles Fernandez, Rafael Sales, Bernat de Haro, Candelaria Lopez-Aguilar, Josefina Lucangelo, Umberto Villar, Jesus Kacmarek, Robert M. Blanch, Lluis TI Automatic detection of ventilatory modes during invasive mechanical ventilation SO CRITICAL CARE LA English DT Article DE Mechanical ventilation; Automatic detection; Ventilatory mode; Information systems in critical care ID PULSE PRESSURE VARIATION; STROKE VOLUME; FLUID RESPONSIVENESS; INTENSIVE-CARE; TIME; MORTALITY; TAXONOMY; SURGERY; ICU AB Background: Expert systems can help alleviate problems related to the shortage of human resources in critical care, offering expert advice in complex situations. Expert systems use contextual information to provide advice to staff. In mechanical ventilation, it is crucial for an expert system to be able to determine the ventilatory mode in use. Different manufacturers have assigned different names to similar or even identical ventilatory modes so an expert system should be able to detect the ventilatory mode. The aim of this study is to evaluate the accuracy of an algorithm to detect the ventilatory mode in use. Methods: We compared the results of a two-step algorithm designed to identify seven ventilatory modes. The algorithm was built into a software platform (BetterCare (R) system, Better Care SL; Barcelona, Spain) that acquires ventilatory signals through the data port of mechanical ventilators. The sample analyzed compared data from consecutive adult patients who underwent > 24 h of mechanical ventilation in intensive care units (ICUs) at two hospitals. We used Cohen's kappa statistics to analyze the agreement between the results obtained with the algorithm and those recorded by ICU staff. Results: We analyzed 486 records from 73 patients. The algorithm correctly labeled the ventilatory mode in 433 (89 %). We found an unweighted Cohen's kappa index of 84.5 % [CI (95 %) = (80.5 %: 88.4 %)]. Conclusions: The computerized algorithm can reliably identify ventilatory mode. C1 [Murias, Gaston] Univ Favaloro, Fac Med, Dept Ciencias Fisiol Farmacol & Bioquim, Clin Bazterr & Clin Santa Isabel, Buenos Aires, DF, Argentina. [Montanya, Jaume; Fernandez, Rafael; Lopez-Aguilar, Josefina; Villar, Jesus; Blanch, Lluis] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. [Montanya, Jaume; Chacon, Encarna; Estruga, Anna; de Haro, Candelaria; Lopez-Aguilar, Josefina; Blanch, Lluis] Univ Autonoma Barcelona, I3PT, Parc Tauli Hosp Univ, C ParcTauli 1, Sabadell 08208, Spain. [Subira, Carles; Fernandez, Rafael] Univ Int Catalunya, Hosp St Joan de Deu, Fundacio Althaia, Serv Med Intens, Manresa, Spain. [Sales, Bernat] Better Care, Barcelona, Spain. [Lucangelo, Umberto] Univ Trieste, Cattinara Hosp, Dept Perioperat Med Intens Care & Emergency, Trieste, Italy. [Villar, Jesus] Hosp Univ Dr Negrin, Res Unit, Las Palmas Gran Canaria, Spain. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Kacmarek, Robert M.] Harvard Med Sch, Dept Anesthesiol, Boston, MA USA. RP Blanch, L (reprint author), Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain.; Blanch, L (reprint author), Univ Autonoma Barcelona, I3PT, Parc Tauli Hosp Univ, C ParcTauli 1, Sabadell 08208, Spain. EM lblanch@tauli.cat RI Fernandez, Rafael/A-9586-2010 OI Fernandez, Rafael/0000-0001-5711-5317 FU Plan Nacional de R+D+I [PI09/91074, PI13/02204]; ISCIII- Subdireccion General de Evaluacion y el Fondo Europeo de Desarrollo Regional (FEDER); CIBER Enfermedades Respiratorias; Fundacion Mapfre; Fundacio Parc Tauli; Plan Avanza [TSI-020302-2008-38]; MCYIN; MITYC (Spain) FX This work was funded by projects PI09/91074 and PI13/02204, integrated in the Plan Nacional de R+D+I and co-funded by the ISCIII- Subdireccion General de Evaluacion y el Fondo Europeo de Desarrollo Regional (FEDER). CIBER Enfermedades Respiratorias, Fundacion Mapfre, Fundacio Parc Tauli, Plan Avanza TSI-020302-2008-38, MCYIN and MITYC (Spain). NR 18 TC 0 Z9 0 U1 2 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X EI 1364-8535 J9 CRIT CARE JI Crit. Care PD AUG 14 PY 2016 VL 20 AR 258 DI 10.1186/s13054-016-1436-9 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA DT6TJ UT WOS:000381616700001 PM 27522580 ER PT J AU Bennett, J Wellman, J Marshall, KA McCague, S Ashtari, M DiStefano-Pappas, J Elci, OU Chung, DC Sun, JW Wright, JF Cross, DR Aravand, P Cyckowski, LL Bennicelli, JL Mingozzi, F Auricchio, A Pierce, EA Ruggiero, J Leroy, BP Simonelli, F High, KA Maguire, AM AF Bennett, Jean Wellman, Jennifer Marshall, Kathleen A. McCague, Sarah Ashtari, Manzar DiStefano-Pappas, Julie Elci, Okan U. Chung, Daniel C. Sun, Junwei Wright, J. Fraser Cross, Dominique R. Aravand, Puya Cyckowski, Laura L. Bennicelli, Jeannette L. Mingozzi, Federico Auricchio, Alberto Pierce, Eric A. Ruggiero, Jason Leroy, Bart P. Simonelli, Francesca High, Katherine A. Maguire, Albert M. TI Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutations: a follow-on phase 1 trial SO LANCET LA English DT Article ID LEBER CONGENITAL AMAUROSIS; ADENOASSOCIATED VIRUS; RETINAL DEGENERATION; CANINE MODEL; VISUAL CYCLE; VISION; IMPROVEMENT; ROD AB Background Safety and efficacy have been shown in a phase 1 dose-escalation study involving a unilateral subretinal injection of a recombinant adeno-associated virus (AAV) vector containing the RPE65 gene (AAV2-hRPE65v2) in individuals with inherited retinal dystrophy caused by RPE65 mutations. This finding, along with the bilateral nature of the disease and intended use in treatment, prompted us to determine the safety of administration of AAV2-hRPE65v2 to the contralateral eye in patients enrolled in the phase 1 study. Methods In this follow-on phase 1 trial, one dose of AAV2-hRPE65v2 (1.5 x 10(11) vector genomes) in a total volume of 300 mu L was subretinally injected into the contralateral, previously uninjected, eyes of 11 children and adults (aged 11-46 years at second administration) with inherited retinal dystrophy caused by RPE65 mutations, 1.71-4.58 years after the initial subretinal injection. We assessed safety, immune response, retinal and visual function, functional vision, and activation of the visual cortex from baseline until 3 year follow-up, with observations ongoing. This study is registered with ClinicalTrials.gov, number NCT01208389. Findings No adverse events related to the AAV were reported, and those related to the procedure were mostly mild (dellen formation in three patients and cataracts in two). One patient developed bacterial endophthalmitis and was excluded from analyses. We noted improvements in efficacy outcomes in most patients without significant immunogenicity. Compared with baseline, pooled analysis of ten participants showed improvements in mean mobility and full-field light sensitivity in the injected eye by day 30 that persisted to year 3 (mobility p=0.0003, white light full-field sensitivity p<0.0001), but no significant change was seen in the previously injected eyes over the same time period (mobility p=0.7398, white light full-field sensitivity p=0.6709). Changes in visual acuity from baseline to year 3 were not significant in pooled analysis in the second eyes or the previously injected eyes (p>0.49 for all time-points compared with baseline). Interpretation To our knowledge, AAV2-hRPE65v2 is the first successful gene therapy administered to the contralateral eye. The results highlight the use of several outcome measures and help to delineate the variables that contribute to maximal benefit from gene augmentation therapy in this disease. C1 [Bennett, Jean; Ashtari, Manzar; Chung, Daniel C.; Sun, Junwei; Aravand, Puya; Bennicelli, Jeannette L.; Maguire, Albert M.] Univ Penn, Ctr Adv Retinal & Ocular Therapeut, Philadelphia, PA 19104 USA. [Bennett, Jean; Ashtari, Manzar; Chung, Daniel C.; Bennicelli, Jeannette L.; Pierce, Eric A.; Maguire, Albert M.] Univ Penn, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19104 USA. [Pierce, Eric A.; Ruggiero, Jason; Maguire, Albert M.] Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA. Univ Penn, Scheie Eye Inst, Philadelphia, PA 19104 USA. [Bennett, Jean; Wellman, Jennifer; Marshall, Kathleen A.; McCague, Sarah; Sun, Junwei; Wright, J. Fraser; Cross, Dominique R.; Mingozzi, Federico; Leroy, Bart P.; High, Katherine A.; Maguire, Albert M.] Childrens Hosp Philadelphia, Ctr Cellular & Mol Therapeut, Philadelphia, PA 19104 USA. [Ashtari, Manzar; Cyckowski, Laura L.] Childrens Hosp Philadelphia, Dept Radiol, Philadelphia, PA 19104 USA. [DiStefano-Pappas, Julie; Elci, Okan U.] Childrens Hosp Philadelphia, Westat Biostat & Data Management Core, Philadelphia, PA 19104 USA. [Pierce, Eric A.; Leroy, Bart P.; Maguire, Albert M.] Childrens Hosp Philadelphia, Dept Ophthalmol, Philadelphia, PA 19104 USA. [Wellman, Jennifer; Chung, Daniel C.; Wright, J. Fraser; High, Katherine A.] Spark Therapeut, Philadelphia, PA USA. [Mingozzi, Federico] Genethon, Immunol & Liver Gene Therapy, Evry, France. [Auricchio, Alberto] Telethon Inst Genet & Med, Naples, Italy. [Auricchio, Alberto] Univ Naples Federico II, Med Genet, Dept Pediat, Naples, Italy. [Pierce, Eric A.] Harvard Med Sch, Ocular Genom Inst, Massachusetts Eye & Ear Infirm, Boston, MA USA. [Leroy, Bart P.] Ghent Univ Hosp, Dept Ophthalmol, Ghent, Belgium. [Leroy, Bart P.] Ghent Univ Hosp, Ctr Med Genet, Ghent, Belgium. [Leroy, Bart P.] Univ Ghent, Ghent, Belgium. [Simonelli, Francesca] Univ Naples 2, Eye Clin, Multidisciplinary Dept Med Surg & Dent Sci, Naples, Italy. [High, Katherine A.] Howard Hughes Med Inst, Philadelphia, PA USA. RP Bennett, J (reprint author), Univ Penn, Ctr Adv Retinal & Ocular Therapeut, Stellar Chance Labs 309c, 422 Curie Blvd, Philadelphia, PA 19104 USA. EM jebennet@mail.med.upenn.edu OI Pierce, Eric/0000-0002-2354-4102 FU Center for Cellular and Molecular Therapeutics at The Children's Hospital of Philadelphia; Spark Therapeutics; US National Institutes of Health; Foundation Fighting Blindness; Institute for Translational Medicine and Therapeutics; Research to Prevent Blindness; Center for Advanced Retinal and Ocular Therapeutics; Mackall Foundation Trust; F M Kirby Foundation; Research Foundation-Flanders FX Center for Cellular and Molecular Therapeutics at The Children's Hospital of Philadelphia, Spark Therapeutics, US National Institutes of Health, Foundation Fighting Blindness, Institute for Translational Medicine and Therapeutics, Research to Prevent Blindness, Center for Advanced Retinal and Ocular Therapeutics, Mackall Foundation Trust, F M Kirby Foundation, and The Research Foundation-Flanders. NR 30 TC 8 Z9 9 U1 9 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD AUG 13 PY 2016 VL 388 IS 10045 BP 661 EP 672 DI 10.1016/S0140-6736(16)30371-3 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA DT1UX UT WOS:000381268700026 PM 27375040 ER PT J AU Levey, EJ Oppenheim, CE Lange, BCL Plasky, NS Harris, BL Lekpeh, GG Kekulah, I Henderson, DC Borba, CPC AF Levey, Elizabeth J. Oppenheim, Claire E. Lange, Brittany C. L. Plasky, Naomi S. Harris, Benjamin L. Lekpeh, G. Gondah Kekulah, Isaac Henderson, David C. Borba, Christina P. C. TI A qualitative analysis of factors impacting resilience among youth in post-conflict Liberia SO CHILD AND ADOLESCENT PSYCHIATRY AND MENTAL HEALTH LA English DT Article DE Liberia; Post-conflict; Qualitative analysis; Youth; Adolescent; Resilience ID PROTECTIVE PROCESSES; CHILDREN; STRESS; PATHWAYS; DISASTER; HEALTH; RISK AB Background: In 2008, 5 years after the Liberian civil war ended, there were an estimated 340,000 orphans in Liberia, 18 % of the total child population of the country. Given that children make up half the population and that these children experienced significant trauma and loss both through direct exposure to the war and then to the Ebola epidemic, and indirectly as a result of the trauma experienced by their parents, the recovery of these children is essential to the recovery of the nation as a whole. The goal of this research was to identify factors contributing to resilience among youth in post-conflict Liberia. Resilience was defined as evidence of adaptive functioning and psychological health. Methods: Seventy-five young people (age 13-18) in the capital city of Monrovia, Liberia were recruited in 2012. Semi-structured interviews were conducted, and demographic data were collected. Interviews were then transcribed and coded thematically. Results: Forty-six of the participants were attending school, and 29 were not enrolled in school. Youth enrolled in school demonstrated greater adaptive functioning. This was particularly true for boys in any school setting and girls attending private school. Youth not attending school were more likely to have lost family members or become estranged from them, and many were also engaging in substance use. Emotion regulation, cognitive flexibility, agency, social intelligence and, in some cases, meaning-making were found in participants who showed resilient outcomes. Conclusions: Caregiver relationships mediate the development of psychological capacities that impact resilience. These findings suggest that youth who have lost a caregiver, many of whom are not attending school, are experiencing a significant ongoing burden in terms of their daily functioning and psychological health in the post-war period and should be the focus of further study and intervention targeting substance use and community reintegration. C1 [Levey, Elizabeth J.] Massachusetts Gen Hosp, Chester M Pierce MD Div Global Psychiat, 5 Longfellow Pl, Boston, MA 02114 USA. [Levey, Elizabeth J.] Harvard Med Sch, 25 Shattuck St, Boston, MA 02115 USA. [Levey, Elizabeth J.] Univ Illinois, Coll Med, 1853 West Polk St, Chicago, IL 60612 USA. [Oppenheim, Claire E.; Henderson, David C.; Borba, Christina P. C.] Boston Med Ctr, Dept Psychiat, 840 Harrison Ave, Boston, MA 02118 USA. [Lange, Brittany C. L.] Univ Oxford, Dept Social Policy & Intervent, Barnett House,32-37 Wellington Sq, Oxford, England. [Plasky, Naomi S.] Johns Hopkins Bloomberg Sch Publ Hlth, 615 North Wolfe St, Baltimore, MD 21205 USA. [Harris, Benjamin L.; Lekpeh, G. Gondah; Kekulah, Isaac] Univ Liberia, AM Dogliotti Coll Med, Monrovia, Liberia. [Henderson, David C.; Borba, Christina P. C.] Boston Univ, Sch Med, 72 East Concord St, Boston, MA 02118 USA. RP Levey, EJ (reprint author), Massachusetts Gen Hosp, Chester M Pierce MD Div Global Psychiat, 5 Longfellow Pl, Boston, MA 02114 USA.; Levey, EJ (reprint author), Harvard Med Sch, 25 Shattuck St, Boston, MA 02115 USA.; Levey, EJ (reprint author), Univ Illinois, Coll Med, 1853 West Polk St, Chicago, IL 60612 USA. EM elevey@partners.org FU National Institutes of Health [T32-MH-093310]; Massachusetts General Hospital Chester M. Pierce, MD Division of Global Psychiatry and Partners Healthcare Center of Expertise in Global Health Travel Award FX This research was supported by an award from the National Institutes of Health (T32-MH-093310). Funding for travel expenses to conduct this project was provided by the Massachusetts General Hospital Chester M. Pierce, MD Division of Global Psychiatry and Partners Healthcare Center of Expertise in Global Health Travel Award. Funding bodies had no role in the design of the study, collection, analysis, interpretation of data or in writing the manuscript. NR 27 TC 1 Z9 1 U1 9 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1753-2000 J9 CHILD ADOL PSYCH MEN JI Child Adolesc. Psychiatry Ment. Health PD AUG 12 PY 2016 VL 10 AR 26 DI 10.1186/s13034-016-0114-7 PG 11 WC Pediatrics; Psychiatry SC Pediatrics; Psychiatry GA EF2PH UT WOS:000390166300001 PM 27525038 ER PT J AU Yaghjyan, L Ghita, GL Rosner, B Farvid, M Bertrand, KA Tamimi, RM AF Yaghjyan, Lusine Ghita, Gabriela L. Rosner, Bernard Farvid, Maryam Bertrand, Kimberly A. Tamimi, Rulla M. TI Adolescent fiber intake and mammographic breast density in premenopausal women SO BREAST CANCER RESEARCH LA English DT Article DE Adolescent diet; Breast density; Fiber intake ID CANCER RISK; POSTMENOPAUSAL WOMEN; DIETARY INTERVENTION; MULTIETHNIC COHORT; SUBSEQUENT RISK; NURSES HEALTH; LIFE-STYLE; LOW-FAT; ASSOCIATION; MENOPAUSE AB Background: To date, there is limited and inconsistent epidemiologic evidence for associations of adolescent diet with mammographic breast density, a strong and consistent predictor of breast cancer. We investigated the association of adolescent fiber intake with mammographic density in premenopausal women. Methods: This study included 743 cancer-free premenopausal women (mean age, 44.9 years) within the Nurses' Health Study II cohort. Percent breast density, absolute dense and non-dense areas were measured from digitized film mammograms using a computer-assisted thresholding technique. Adolescent and adult diet were assessed with a food frequency questionnaire; energy-adjusted nutrient intakes were estimated for each food item. Information regarding breast cancer risk factors was obtained from baseline or biennial questionnaires closest to the mammogram date. We used generalized linear regression to quantify associations between quartiles of adolescent fiber intake and each of the breast density measures, adjusted for potential confounders. Associations were examined separately for total fiber intake; fiber from fruits, vegetables, legumes, and cereal; and food sources of fiber (fruits, vegetables, and nuts). Results: In multivariable analyses, total fiber intake during adolescence was not associated with percent breast density (p for trend = 0.64), absolute dense area (p for trend = 0.80), or non-dense area (p for trend = 0.75). Similarly, neither consumption of fiber from fruits, vegetables, legumes, or cereal nor specific sources of fiber intake (fruits, vegetables, or nuts) during adolescence were associated with any of the mammographic density phenotypes. Conclusions: Our findings do not support the hypothesis that adolescent fiber intake is associated with premenopausal mammographic breast density. C1 [Yaghjyan, Lusine] Univ Florida, Dept Epidemiol, Coll Publ Hlth & Hlth Profess, 2004 Mowry Rd, Gainesville, FL 32610 USA. [Yaghjyan, Lusine; Ghita, Gabriela L.] Univ Florida, Coll Med, 2004 Mowry Rd, Gainesville, FL 32610 USA. [Ghita, Gabriela L.] Univ Florida, Dept Biostat, Coll Publ Hlth & Hlth Profess, Gainesville, FL USA. [Rosner, Bernard] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Rosner, Bernard] Harvard Med Sch, Boston, MA USA. [Farvid, Maryam] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Farvid, Maryam] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Harvard Massachusetts Gen Hosp, Ctr Genom Vulnerable Populat & Hlth Dispar, Boston, MA 02114 USA. [Bertrand, Kimberly A.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. RP Yaghjyan, L (reprint author), Univ Florida, Dept Epidemiol, Coll Publ Hlth & Hlth Profess, 2004 Mowry Rd, Gainesville, FL 32610 USA.; Yaghjyan, L (reprint author), Univ Florida, Coll Med, 2004 Mowry Rd, Gainesville, FL 32610 USA. EM lyaghjyan@ufl.edu FU National Cancer Institute at the National Institutes of Health [CA131332, CA087969, CA175080, UM1 CA186107, UM1 CA176726]; Avon Foundation for Women; Susan G. Komen for the Cure(R); Breast Cancer Research Foundation; Simeon J. Fortin Charitable Foundation, Bank of America, NA, Co-Trustee FX This work was supported by the National Cancer Institute at the National Institutes of Health [CA131332, CA087969, CA175080 to RMT, UM1 CA186107 to MS, UM1 CA176726 to WW], Avon Foundation for Women, Susan G. Komen for the Cure (R), and Breast Cancer Research Foundation. KAB is supported in part by the Simeon J. Fortin Charitable Foundation, Bank of America, NA, Co-Trustee. NR 56 TC 0 Z9 0 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PD AUG 12 PY 2016 VL 18 AR 85 DI 10.1186/s13058-016-0747-8 PG 8 WC Oncology SC Oncology GA DW1VI UT WOS:000383430600001 PM 27520794 ER PT J AU Lee, CJ Ahn, H Lee, SB Shin, JY Park, WY Kim, JI Lee, J Ryu, H Kim, S AF Lee, Chai-Jin Ahn, Hongryul Lee, Sean Bong Shin, Jong-Yeon Park, Woong-Yang Kim, Jong-Il Lee, Junghee Ryu, Hoon Kim, Sun TI Integrated analysis of omics data using microRNA-target mRNA network and PPI network reveals regulation of Gnai1 function in the spinal cord of Ews/Ewsr1 KO mice SO BMC MEDICAL GENOMICS LA English DT Article; Proceedings Paper CT 5th Translational Bioinformatics Conference (TBC) CY NOV 07-09, 2015 CL Tokyo, JAPAN DE EWS; Ewsr1; Gnai1; MMIA; PPI; Network analysis ID SARCOMA GENE EWS; EWINGS-SARCOMA; TUMORS; PROTEIN AB Background: Multifunctional transcription factor (TF) gene EWS/EWSR1 is involved in various cellular processes such as transcription regulation, noncoding RNA regulation, splicing regulation, genotoxic stress response, and cancer generation. Role of a TF gene can be effectively studied by measuring genome-wide gene expression, i.e., transcriptome, in an animal model of Ews/Ewsr1 knockout (KO). However, when a TF gene has complex multi-functions, conventional approaches such as differentially expressed genes (DEGs) analysis are not successful to characterize the role of the EWS gene. In this regard, network-based analyses that consider associations among genes are the most promising approach. Methods: Networks are constructed and used to show associations among biological entities at various levels, thus different networks represent association at different levels. Taken together, in this paper, we report contributions on both computational and biological sides. Results: Contribution on the computational side is to develop a novel computational framework that combines miRNA-gene network and protein-protein interaction network information to characterize the multifunctional role of EWS gene. On the biological side, we report that EWS regulates G-protein, Gnai1, in the spinal cord of Ews/Ewsr1 KO mice using the two biological network integrated analysis method. Neighbor proteins of Gnai1, G-protein complex subunits Gnb1, Gnb2 and Gnb4 were also down-regulated at their gene expression level. Interestingly, up-regulated genes, such as Rgs1 and Rgs19, are linked to the inhibition of Gnai1 activities. We further verified the altered expression of Gnai1 by qRT-PCR in Ews/Ewsr1 KO mice. Conclusions: Our integrated analysis of miRNA-transcriptome network and PPI network combined with qRT-PCR verifies that Gnai1 function is impaired in the spinal cord of Ews/Ewsr1 KO mice. C1 [Lee, Chai-Jin; Kim, Sun] Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul 151747, South Korea. [Ahn, Hongryul; Kim, Sun] Seoul Natl Univ, Dept Comp Sci & Engn, Seoul 151744, South Korea. [Kim, Sun] Seoul Natl Univ, Bioinformat Inst, Seoul 151747, South Korea. [Lee, Sean Bong] Tulane Univ, Sch Med, Dept Pathol & Lab Med, 1430 Tulane Ave, New Orleans, LA 70112 USA. [Shin, Jong-Yeon; Kim, Jong-Il] Seoul Natl Univ, Coll Med, Genome Med Inst, Seoul 110799, South Korea. [Shin, Jong-Yeon; Kim, Jong-Il] Seoul Natl Univ, Coll Med, Dept Biochem, Seoul 110799, South Korea. [Park, Woong-Yang] Sungkyunkwan Univ, Samsung Med Ctr, Samsung Genome Inst, Seoul 135710, South Korea. [Park, Woong-Yang] Sungkyunkwan Univ, Samsung Adv Inst Hlth Sci & Technol, Dept Hlth Sci & Technol, Seoul 135710, South Korea. [Lee, Junghee; Ryu, Hoon] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Lee, Junghee; Ryu, Hoon] Boston Univ, Alzheimers Dis Ctr, Boston, MA 02118 USA. [Lee, Junghee; Ryu, Hoon] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Ryu, Hoon] Korea Inst Sci & Technol, Brain Sci Inst, Ctr Neuromed, Seoul 136791, South Korea. RP Kim, S (reprint author), Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul 151747, South Korea.; Ryu, H (reprint author), VA Boston Healthcare Syst, Boston, MA 02130 USA. EM hoonryu@bu.edu; sunkim.bioinfo@snu.ac.kr RI KIM, JONG-IL/D-1019-2011 OI KIM, JONG-IL/0000-0002-7240-3744 FU NINDS NIH HHS [R01 NS067283] NR 29 TC 0 Z9 0 U1 2 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1755-8794 J9 BMC MED GENOMICS JI BMC Med. Genomics PD AUG 12 PY 2016 VL 9 SU 1 AR 33 DI 10.1186/s12920-016-0195-4 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA DT2OH UT WOS:000381319300006 PM 27534535 ER PT J AU Sanders-Jackson, A Tan, ASL Bigman, CA Mello, S Niederdeppe, J AF Sanders-Jackson, Ashley Tan, Andy S. L. Bigman, Cabral A. Mello, Susan Niederdeppe, Jeff TI To Regulate or Not to Regulate? Views on Electronic Cigarette Regulations and Beliefs about the Reasons for and against Regulation SO PLOS ONE LA English DT Article ID ADOLESCENTS; EXPOSURE; RISK AB Background Policies designed to restrict marketing, access to, and public use of electronic cigarettes (e-cigarettes) are increasingly under debate in various jurisdictions in the US. Little is known about public perceptions of these policies and factors that predict their support or opposition. Methods Using a sample of US adults from Amazon Mechanical Turk in May 2015, this paper identifies beliefs about the benefits and costs of regulating e-cigarettes and identifies which of these beliefs predict support for e-cigarette restricting policies. Results A higher proportion of respondents agreed with 8 different reasons to regulate e-cigarettes (48.5% to 83.3% agreement) versus 7 reasons not to regulate e-cigarettes (11.5% to 18.9%). The majority of participants agreed with 7 out of 8 reasons for regulation. When all reasons to regulate or not were included in a final multivariable model, beliefs about protecting people from secondhand vapor and protecting youth from trying e-cigarettes significantly predicted stronger support for e-cigarette restricting policies, whereas concern about government intrusion into individual choices was associated with reduced support. Discussion This research identifies key beliefs that may underlie public support or opposition to policies designed to regulate the marketing and use of e-cigarettes. Advocates on both sides of the issue may find this research valuable in developing strategic campaigns related to the issue. Implications Specific beliefs of potential benefits and costs of e-cigarette regulation (protecting youth, preventing exposure to secondhand vapor, and government intrusion into individual choices) may be effectively deployed by policy makers or health advocates in communicating with the public. C1 [Sanders-Jackson, Ashley] Michigan State Univ, Dept Advertising & Publ Relat, Coll Commun Arts & Sci, 404 Wilson Rd, Lansing, MI 48824 USA. [Tan, Andy S. L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Kresge Bldg,677 Huntington Ave, Boston, MA 02115 USA. [Bigman, Cabral A.] Univ Illinois, Coll Liberal Arts & Sci, Dept Commun, 3001 Lincoln Hall,702 S Wright St, Urbana, IL USA. [Mello, Susan] Northeastern Univ, Dept Commun Studies, Coll Arts Media & Design, 360 Huntington Ave, Boston, MA 02115 USA. [Niederdeppe, Jeff] Cornell Univ, Coll Agr & Life Sci, Dept Commun, 476 Mann Lib Bldg, Ithaca, NY 14853 USA. [Tan, Andy S. L.] Dana Farber Canc Inst, Div Populat Sci, Ctr Community Based Res, 450 Brookline Ave LW662, Boston, MA 02115 USA. RP Sanders-Jackson, A (reprint author), Michigan State Univ, Dept Advertising & Publ Relat, Coll Commun Arts & Sci, 404 Wilson Rd, Lansing, MI 48824 USA. EM sande411@msu.edu FU NHLBI of the National Institutes of Health [T32HL00703440] FX Research reported in this paper was supported by NHLBI of the National Institutes of Health under award number T32HL00703440. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 31 TC 0 Z9 0 U1 2 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 12 PY 2016 VL 11 IS 8 AR e0161124 DI 10.1371/journal.pone.0161124 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DT3LI UT WOS:000381382100052 ER PT J AU Tan-Shalaby, JL Carrick, J Edinger, K Genovese, D Liman, AD Passero, VA Shah, RB AF Tan-Shalaby, Jocelyn L. Carrick, Jennifer Edinger, Krystal Genovese, Dana Liman, Andrew D. Passero, Vida A. Shah, Rashmikant B. TI Modified Atkins diet in advanced malignancies - final results of a safety and feasibility trial within the Veterans Affairs Pittsburgh Healthcare System SO NUTRITION & METABOLISM LA English DT Article ID KETOGENIC DIET; METABOLIC MANAGEMENT; ADVANCED CANCER; KETONE-BODIES; EXPRESSION; THERAPY; LEPTIN; CELLS; GLIOBLASTOMA; EPILEPSY AB Background: Dysfunctional mitochondrial processes limit malignant cells ability to use energy from fatty acids and ketones. Animal studies using ketogenic diets for cancer show encouraging results. We tested the diet's safety and feasibility in cancer patients across a broad variety of solid tumors. Methods: We recruited 17 advanced cancer patients who were not on chemotherapy. They consumed 20 to 40 g of carbohydrates daily with evaluations performed weekly until week 4, then every 4 weeks until 16 weeks. Quality of life questionnaires monitored for tolerability and compliance. Positron emission/computerized tomography was ordered at baseline, 4,8 and 16 weeks. Student t-testing evaluated differences between baseline and last visit scores for quality of life, weight, body mass index, and serum parameters. Correlations between weight loss and serum ketones, glucose, lipids and creatinine were done. Two-tailed unpaired t-testing of the mean weight loss compared responders against non-responders. Results: Eleven out of seventeen enrolled patients were evaluable. Mean age was 65+/- 11.7 years, weight 203 +/- 4.98 lbs. (92 +/- 2.3 kgs.) and previous treatment failures was 1.7, +/- 0.97. All lost significant weight with hematologic, biochemical and lipid tests remaining stable. Quality of life scores slightly improved. At 4,8 and 16 weeks, six (54.5 %), five (45.4 %) and four (36 %) patients were stable or improved. We observed no correlations between serum glucose, ketones or lipids. Clinical response did not correlate with ketosis or glycemia. Responders (stable disease or partial responders) lost statistically more weight than non-responders. Dietary compliance was difficult. Only three patients continued dieting past 16 weeks. Out of these, two patients developed brain metastases and were on steroids. They survived 80 and 116 weeks respectively. The third patient underwent residual tumor resection and has no disease at 131 weeks. Conclusions: Modified Atkins diets are safe and feasible in advanced cancer. Quality of life was preserved. Patients who lost at least 10 % of their body weight responded the best. Steroid intake affected optimal ketone and glucose levels. Despite this, survival improved in some melanoma and lung cancer patients. Further studies are recommended. C1 [Tan-Shalaby, Jocelyn L.; Carrick, Jennifer; Edinger, Krystal; Genovese, Dana; Liman, Andrew D.; Passero, Vida A.; Shah, Rashmikant B.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA. [Tan-Shalaby, Jocelyn L.; Edinger, Krystal; Genovese, Dana; Liman, Andrew D.; Passero, Vida A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. RP Tan-Shalaby, JL (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA.; Tan-Shalaby, JL (reprint author), Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. EM jocelyn.tan@va.gov FU Veterans Research Foundation of Pittsburgh FX Tammy Cobaugh for her help in drafting the initial trial protocol; Samantha Bonant, Alanna Caffas and and Sharlene Wylie for research assistance Becky Englert RN, Lynn Marmarelli RN and Pamela Malicki RN for patient recruitment and followup; Mary Kay Winkelman for her secretarial contribution; Joseph Mikolic for statistical analysis; Mariam Shalaby for proofreading and technical support. I am grateful to the Veterans Research Foundation of Pittsburgh for their overall support and confidence in this project. I would like to thank Dr. Thomas Seyfried, Professor of Biology at Boston College, for his critical comments and valuable feedback during the editing and revision of the final manuscript. NR 28 TC 2 Z9 2 U1 7 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-7075 J9 NUTR METAB JI Nutr. Metab. PD AUG 12 PY 2016 VL 13 AR 52 DI 10.1186/s12986-016-0113-y PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DT9CY UT WOS:000381794300001 PM 27525031 ER PT J AU Bazari, H Palmer, WE Baron, JM Armstrong, K AF Bazari, Hasan Palmer, William E. Baron, Jason M. Armstrong, Katrina TI Case 24-2016: A 66-Year-Old Man with Malaise, Weakness, and Hypercalcemia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ALKALI SYNDROME; MANAGEMENT C1 [Bazari, Hasan; Armstrong, Katrina] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Palmer, William E.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. [Baron, Jason M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Bazari, Hasan; Armstrong, Katrina] Harvard Med Sch, Dept Med, Boston, MA USA. [Palmer, William E.] Harvard Med Sch, Dept Radiol, Boston, MA USA. [Baron, Jason M.] Harvard Med Sch, Dept Pathol, Boston, MA USA. RP Bazari, H (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. FU International Business Machines; GlaxoSmithKline FX Dr. Bazari reports holding stock in Pfizer; Dr. Baron, receiving grant support to his institution from International Business Machines; and Dr. Armstrong, receiving consulting fees from GlaxoSmithKline. No other potential conflict of interest relevant to this article was reported. NR 14 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 11 PY 2016 VL 375 IS 6 BP 567 EP 577 DI 10.1056/NEJMcpc1503829 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA DU4OT UT WOS:000382193100011 PM 27509105 ER PT J AU Ghogawala, Z Barker, FG Benzel, EC AF Ghogawala, Zoher Barker, Fred G., II Benzel, Edward C. TI Fusion Surgery for Lumbar Spinal Stenosis REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID SPONDYLOLISTHESIS C1 [Ghogawala, Zoher] Lahey Hosp & Med Ctr, Burlington, MA USA. [Barker, Fred G., II] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Benzel, Edward C.] Cleveland Clin Fdn, 9500 Euclid Ave, Cleveland, OH 44195 USA. RP Ghogawala, Z (reprint author), Lahey Hosp & Med Ctr, Burlington, MA USA. EM zoher.ghogawala@lahey.org NR 2 TC 1 Z9 1 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 11 PY 2016 VL 375 IS 6 BP 600 EP 601 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA DU4OT UT WOS:000382193100021 PM 27517105 ER PT J AU Matsumura, J Monteleone, P Rosenfield, K AF Matsumura, Jon Monteleone, Peter Rosenfield, Kenneth TI Stenting versus Surgery for Carotid Stenosis REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Matsumura, Jon] Univ Wisconsin, Madison, WI 53706 USA. [Monteleone, Peter; Rosenfield, Kenneth] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Matsumura, J (reprint author), Univ Wisconsin, Madison, WI 53706 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 11 PY 2016 VL 375 IS 6 BP 603 EP 604 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA DU4OT UT WOS:000382193100027 PM 27509114 ER PT J AU Hunter, ZR Xu, L Yang, G Tsakmaklis, N Vos, JM Liu, X Chen, J Manning, RJ Chen, JJG Brodsky, P Patterson, CJ Gustine, J Dubeau, T Castillo, JJ Anderson, KC Munshi, NM Treon, SP AF Hunter, Zachary R. Xu, Lian Yang, Guang Tsakmaklis, Nicholas Vos, Josephine M. Liu, Xia Chen, Jie Manning, Robert J. Chen, Jiaji G. Brodsky, Philip Patterson, Christopher J. Gustine, Joshua Dubeau, Toni Castillo, Jorge J. Anderson, Kenneth C. Munshi, Nikhil M. Treon, Steven P. TI Transcriptome sequencing reveals a profile that corresponds to genomic variants in Waldenstrom macroglobulinemia SO BLOOD LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; B-CELL; MYD88 L265P; SOMATIC MUTATION; TUMOR-SUPPRESSOR; MONOCLONAL GAMMOPATHY; NEGATIVE REGULATOR; MULTIPLE-MYELOMA; DNA METHYLATION; CXCR4 MUTATIONS AB Whole-genome sequencing has identified highly prevalent somatic mutations including MYD88, CXCR4, and ARID1A in Waldenstrom macroglobulinemia (WM). The impact of these and other somatic mutations on transcriptional regulation in WM remains to be clarified. We performed next-generation transcriptional profiling in 57 WM patients and compared findings to healthy donor B cells. Compared with healthy donors, WM patient samples showed greatly enhanced expression of the VDJ recombination genes DNTT, RAG1, and RAG2, but not AICDA. Genes related to CXCR4 signaling were also upregulated and included CXCR4, CXCL12, and VCAM1 regardless of CXCR4 mutation status, indicating a potential role for CXCR4 signaling in all WM patients. The WM transcriptional profile was equally dissimilar to healthy memory B cells and circulating B cells likely due increased differentiation rather than cellular origin. The profile for CXCR4 mutations corresponded to diminished B-cell differentiation and suppression of tumor suppressors upregulated by MYD88 mutations in a manner associated with the suppression of TLR4 signaling relative to those mutated for MYD88 alone. Promoter methylation studies of top findings failed to explain this suppressive effect but identified aberrant methylation patterns in MYD88 wild-type patients. CXCR4 and MYD88 transcription were negatively correlated, demonstrated allele-specific transcription bias, and, along with CXCL13, were associated with bone marrow disease involvement. Distinct gene expression profiles for patients with wild-type MYD88, mutated ARID1A, familial predisposition to WM, chr6q deletions, chr3q amplifications, and trisomy 4 are also described. The findings provide novel insights into the molecular pathogenesis and opportunities for targeted therapeutic strategies for WM. (Blood. 2016;128(6):827-838) C1 [Hunter, Zachary R.; Xu, Lian; Yang, Guang; Tsakmaklis, Nicholas; Vos, Josephine M.; Liu, Xia; Chen, Jie; Manning, Robert J.; Chen, Jiaji G.; Brodsky, Philip; Patterson, Christopher J.; Gustine, Joshua; Dubeau, Toni; Castillo, Jorge J.; Treon, Steven P.] Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, M547,450 Brookline Ave, Boston, MA 02215 USA. [Hunter, Zachary R.; Yang, Guang; Castillo, Jorge J.; Anderson, Kenneth C.; Munshi, Nikhil M.; Treon, Steven P.] Harvard Med Sch, Dept Med, Boston, MA 02215 USA. [Anderson, Kenneth C.; Munshi, Nikhil M.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02215 USA. [Munshi, Nikhil M.] Boston VA Healthcare Syst, Dept Med, West Roxbury, MA USA. RP Treon, SP (reprint author), Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, M547,450 Brookline Ave, Boston, MA 02215 USA. EM steven_treon@dfci.harvard.edu OI Hunter, Zachary/0000-0002-1689-1691; Castillo, Jorge/0000-0001-9490-7532 FU Leukemia & Lymphoma Society; International Waldenstrom's Macroglobulinemia Foundation; National Institutes of Health; National Cancer Institute [5P50CA100707-12]; Orzag Family Fund for WM Research FX This work was supported by Peter S. Bing, a Translational Research grant from the Leukemia & Lymphoma Society, a grant from the International Waldenstrom's Macroglobulinemia Foundation, a National Institutes of Health, National Cancer Institute Spore 5P50CA100707-12 Research Development Award, and the Orzag Family Fund for WM Research. NR 71 TC 5 Z9 5 U1 4 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 AUG 11 PY 2016 VL 128 IS 6 BP 827 EP 838 DI 10.1182/blood-2016-03-708263 PG 12 WC Hematology SC Hematology GA DW7KV UT WOS:000383830500014 PM 27301862 ER PT J AU Horvath, S Gurven, M Levine, ME Trumble, BC Kaplan, H Allayee, H Ritz, BR Chen, B Lu, AT Rickabaugh, TM Jamieson, BD Sun, D Li, SX Chen, W Quintana-Murci, L Fagny, M Kobor, MS Tsao, PS Reiner, AP Edlefsen, KL Absher, D Assimes, TL AF Horvath, Steve Gurven, Michael Levine, Morgan E. Trumble, Benjamin C. Kaplan, Hillard Allayee, Hooman Ritz, Beate R. Chen, Brian Lu, Ake T. Rickabaugh, Tammy M. Jamieson, Beth D. Sun, Dianjianyi Li, Shengxu Chen, Wei Quintana-Murci, Lluis Fagny, Maud Kobor, Michael S. Tsao, Philip S. Reiner, Alexander P. Edlefsen, Kerstin L. Absher, Devin Assimes, Themistocles L. TI An epigenetic clock analysis of race/ethnicity, sex, and coronary heart disease SO GENOME BIOLOGY LA English DT Article DE DNA methylation; Epigenetic clock; Race; Gender; Aging; Coronary heart disease; Hispanic paradox; Black/white mortality cross-over ID DNA METHYLATION AGE; HUMAN BRAIN; ALZHEIMERS-DISEASE; TELOMERE LENGTH; PARKINSONS-DISEASE; AFRICAN-AMERICANS; UNITED-STATES; HUMAN TISSUES; ALL-CAUSE; T-CELLS AB Background: Epigenetic biomarkers of aging (the "epigenetic clock") have the potential to address puzzling findings surrounding mortality rates and incidence of cardio-metabolic disease such as: (1) women consistently exhibiting lower mortality than men despite having higher levels of morbidity; (2) racial/ethnic groups having different mortality rates even after adjusting for socioeconomic differences; (3) the black/white mortality cross-over effect in late adulthood; and (4) Hispanics in the United States having a longer life expectancy than Caucasians despite having a higher burden of traditional cardio-metabolic risk factors. Results: We analyzed blood, saliva, and brain samples from seven different racial/ethnic groups. We assessed the intrinsic epigenetic age acceleration of blood (independent of blood cell counts) and the extrinsic epigenetic aging rates of blood (dependent on blood cell counts and tracks the age of the immune system). In blood, Hispanics and Tsimane Amerindians have lower intrinsic but higher extrinsic epigenetic aging rates than Caucasians. African-Americans have lower extrinsic epigenetic aging rates than Caucasians and Hispanics but no differences were found for the intrinsic measure. Men have higher epigenetic aging rates than women in blood, saliva, and brain tissue. Conclusions: Epigenetic aging rates are significantly associated with sex, race/ethnicity, and to a lesser extent with CHD risk factors, but not with incident CHD outcomes. These results may help elucidate lower than expected mortality rates observed in Hispanics, older African-Americans, and women. C1 [Horvath, Steve; Levine, Morgan E.; Lu, Ake T.] Univ Calif Los Angeles, David Geffen Sch Med, Human Genet, Los Angeles, CA 90095 USA. [Horvath, Steve] Univ Calif Los Angeles, Sch Publ Hlth, Biostat, Los Angeles, CA 90095 USA. [Gurven, Michael; Trumble, Benjamin C.] Univ Calif Santa Barbara, Dept Anthropol, Santa Barbara, CA 93106 USA. [Kaplan, Hillard] Univ New Mexico, Dept Anthropol, Albuquerque, NM 87131 USA. [Allayee, Hooman] Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA. [Allayee, Hooman] Univ Southern Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90089 USA. [Ritz, Beate R.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90095 USA. [Chen, Brian] NIA, Longitudinal Studies Sect, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA. [Rickabaugh, Tammy M.; Jamieson, Beth D.] Univ Calif Los Angeles, AIDS Inst, Dept Med, Div Hematol Oncol, Los Angeles, CA USA. [Sun, Dianjianyi; Li, Shengxu; Chen, Wei] Tulane Univ, Dept Epidemiol, New Orleans, LA 70112 USA. [Quintana-Murci, Lluis] CNRS, Inst Pasteur, URA3012, URA3012,Unit Human Evolutionary Genet, F-75015 Paris, France. [Fagny, Maud] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Fagny, Maud] Dana Farber Canc Inst, Dept Computat Biol & Biostat, Boston, MA 02115 USA. [Kobor, Michael S.] Univ British Columbia, Ctr Mol Med & Therapeut, Child & Family Res Inst, Vancouver, BC V5Z 4H4, Canada. [Kobor, Michael S.] Univ British Columbia, Dept Med Genet, Vancouver, BC V5Z 4H4, Canada. [Tsao, Philip S.; Assimes, Themistocles L.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Tsao, Philip S.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Reiner, Alexander P.] Univ Washington, Fred Hutchinson Canc Res Ctr, Dept Epidemiol, Seattle, WA 98109 USA. [Edlefsen, Kerstin L.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Absher, Devin] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA. RP Horvath, S (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Human Genet, Los Angeles, CA 90095 USA.; Horvath, S (reprint author), Univ Calif Los Angeles, Sch Publ Hlth, Biostat, Los Angeles, CA 90095 USA. EM shorvath@mednet.ucla.edu RI Assimes, Themistocles/D-9696-2015; OI Assimes, Themistocles/0000-0003-2349-0009; Horvath, Steve/0000-0002-4110-3589; Fagny, Maud/0000-0002-7740-2521 FU NIH/NHLBI [60442456 BAA23]; National Institutes of Health NIH/NIA [1U34AG051425-01]; National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; NIEHS [RO1ES10544, R21 ES024356]; NIH/NIA [R01AG024119, R56AG02411]; [P30AG10161]; [R01AG17917]; [RF1AG15819]; [R01AG36042] FX This study was supported by NIH/NHLBI 60442456 BAA23 (Assimes, Absher, Horvath), National Institutes of Health NIH/NIA 1U34AG051425-01 (Horvath). The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. The PEG data were supported by NIEHS RO1ES10544 (Ritz) and NIEHS R21 ES024356 (Horvath, Ritz). Gurven and Trumble were funded by NIH/NIA R01AG024119 and R56AG02411. The Religious Order study and Rush Memory and Aging Project (brain dataset 6) were funded by P30AG10161, R01AG17917, RF1AG15819, and R01AG36042. NR 89 TC 4 Z9 4 U1 18 U2 27 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PD AUG 11 PY 2016 VL 17 AR 171 DI 10.1186/s13059-016-1030-0 PG 22 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA DT8EH UT WOS:000381721400001 PM 27511193 ER PT J AU Garcia-Caceres, C Quarta, C Varela, L Gao, YQ Gruber, T Legutko, B Jastroch, M Johansson, P Ninkovic, J Yi, CX Thuc, OL Szigeti-Buck, K Cai, WK Meyer, CW Pfluger, PT Fernandez, AM Luquet, S Woods, SC Torres-Aleman, I Kahn, CR Gotz, M Horvath, TL Tschop, MH AF Garcia-Caceres, Cristina Quarta, Carmelo Varela, Luis Gao, Yuanqing Gruber, Tim Legutko, Beata Jastroch, Martin Johansson, Pia Ninkovic, Jovica Yi, Chun-Xia Thuc, Ophelia Le Szigeti-Buck, Klara Cai, Weikang Meyer, Carola W. Pfluger, Paul T. Fernandez, Ana M. Luquet, Serge Woods, Stephen C. Torres-Aleman, Ignacio Kahn, C. Ronald Goetz, Magdalena Horvath, Tamas L. Tschoep, Matthias H. TI Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability SO CELL LA English DT Article ID BODY-WEIGHT; NEURONAL DYSFUNCTION; ALZHEIMERS-DISEASE; ENERGY-METABOLISM; BARRIER; LEPTIN; CELLS; TRANSPORTER; CIRCUITS; MICE AB We report that astrocytic insulin signaling co-regulates hypothalamic glucose sensing and systemic glucose metabolism. Postnatal ablation of insulin receptors (IRs) in glial fibrillary acidic protein (GFAP)-expressing cells affects hypothalamic astrocyte morphology, mitochondrial function, and circuit connectivity. Accordingly, astrocytic IR ablation reduces glucose-induced activation of hypothalamic proopio-melanocortin (POMC) neurons and impairs physiological responses to changes in glucose availability. Hypothalamus-specific knockout of astrocytic IRs, as well as postnatal ablation by targeting glutamate aspartate transporter (GLAST)-expressing cells, replicates such alterations. A normal response to altering directly CNS glucose levels in mice lacking astrocytic IRs indicates a role in glucose transport across the blood-brain barrier (BBB). This was confirmed in vivo in GFAP-IR KO mice by using positron emission tomography and glucose monitoring in cerebral spinal fluid. We conclude that insulin signaling in hypothalamic astrocytes co-controls CNS glucose sensing and systemic glucose metabolism via regulation of glucose uptake across the BBB. C1 [Garcia-Caceres, Cristina; Quarta, Carmelo; Gao, Yuanqing; Gruber, Tim; Legutko, Beata; Jastroch, Martin; Yi, Chun-Xia; Thuc, Ophelia Le; Meyer, Carola W.; Pfluger, Paul T.; Tschoep, Matthias H.] Helmholtz Zentrum Munchen, Helmholtz Diabet Ctr HDC, D-85764 Neuherberg, Germany. [Garcia-Caceres, Cristina; Quarta, Carmelo; Gao, Yuanqing; Gruber, Tim; Legutko, Beata; Jastroch, Martin; Yi, Chun-Xia; Thuc, Ophelia Le; Meyer, Carola W.; Pfluger, Paul T.; Tschoep, Matthias H.] Helmholtz Zentrum Munchen, German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany. [Garcia-Caceres, Cristina; Quarta, Carmelo; Gao, Yuanqing; Gruber, Tim; Legutko, Beata; Jastroch, Martin; Yi, Chun-Xia; Thuc, Ophelia Le; Meyer, Carola W.; Pfluger, Paul T.; Tschoep, Matthias H.] Tech Univ Munich, Div Metab Dis, D-80333 Munich, Germany. [Varela, Luis; Szigeti-Buck, Klara; Horvath, Tamas L.] Yale Univ, Sch Med, Comparat Med Sect, Program Integrat Cell Signaling & Neurobiol Metab, New Haven, CT 06520 USA. [Johansson, Pia; Ninkovic, Jovica; Goetz, Magdalena] Helmholtz Zentrum Munchen, Inst Stem Cell Res Ctr, D-85764 Neuherberg, Germany. [Johansson, Pia; Ninkovic, Jovica; Goetz, Magdalena] Ludwigs Maximilians Univ, Biomed Ctr, Physiol Genom, D-80336 Munich, Germany. [Johansson, Pia; Ninkovic, Jovica; Goetz, Magdalena] Ludwigs Maximilians Univ, Biomed Ctr, 7SYNERGY, Excellence Cluster Syst Neurol, D-80336 Munich, Germany. [Cai, Weikang; Kahn, C. Ronald] Brigham & Womens Hosp, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA. [Cai, Weikang; Kahn, C. Ronald] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Cai, Weikang; Kahn, C. Ronald] Harvard Med Sch, Boston, MA 02115 USA. [Fernandez, Ana M.; Torres-Aleman, Ignacio] CSIC, Inst Cajal, E-28002 Madrid, Spain. [Luquet, Serge] Univ Paris Diderot, Sorbonne Paris Cite, Unite Biol Fonct & Adaptat, CNRS UMR 8251, F-75205 Paris, France. [Woods, Stephen C.] Univ Cincinnati, Dept Psychiat & Behav Neurosci, 2170 Galbraith Ave, Cincinnati, OH 45237 USA. RP Tschop, MH (reprint author), Helmholtz Zentrum Munchen, Helmholtz Diabet Ctr HDC, D-85764 Neuherberg, Germany.; Tschop, MH (reprint author), Helmholtz Zentrum Munchen, German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany.; Tschop, MH (reprint author), Tech Univ Munich, Div Metab Dis, D-80333 Munich, Germany. EM tschoep@helmholtz-muenchen.de RI Garcia-Caceres, Cristina/O-6601-2016; Yi, Chun-Xia/J-4068-2016; OI Garcia-Caceres, Cristina/0000-0001-6376-9448; Yi, Chun-Xia/0000-0003-1184-4615; Torres Aleman, Ignacio/0000-0001-8107-7947; luquet, serge/0000-0001-8668-6645 FU Helmholtz Alliance ICEMED - Imaging and Curing Environmental Metabolic Diseases; Humboldt Foundation; Initiative and Networking Fund of the Helmholtz Association; Deutsches Zentrum fur DiabetesForschung (DZD); Institute of Advanced Studies of Technische Universitat Munchen (IAS-TUM Hans-Fischer); DFG [SFB 1123, SFB 870, SFB 1757] FX The authors thank Heicko Lickert and Silke Morin for helpful discussion and support and Lewis Norris, Clarita Mergen, Veronica Casquero Garcia, Olavi Jarvinen, and Nicole Wiegert for excellent technical assistance. This work was funded, in part, by the Helmholtz Alliance ICEMED - Imaging and Curing Environmental Metabolic Diseases, the Humboldt Foundation (to M.H.T.), through the Initiative and Networking Fund of the Helmholtz Association and Deutsches Zentrum fur DiabetesForschung (DZD). This work also received funding from the Institute of Advanced Studies of Technische Universitat Munchen (IAS-TUM Hans-Fischer Senior Fellowship to T.L.H.) and from DFG funding (SFB 1123 to M.H.T; SFB 870 and SPP 1757 to M.G.). NR 40 TC 12 Z9 12 U1 22 U2 25 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD AUG 11 PY 2016 VL 166 IS 4 BP 867 EP 880 DI 10.1016/j.cell.2016.07.028 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DU5NO UT WOS:000382258700011 PM 27518562 ER PT J AU Goncalves, KA Silberstein, L Li, SP Severe, N Hu, MFG Yang, HL Scadden, DT Hu, GF AF Goncalves, Kevin A. Silberstein, Lev Li, Shuping Severe, Nicolas Hu, Miaofen G. Yang, Hailing Scadden, David T. Hu, Guo-fu TI Angiogenin Promotes Hematopoietic Regeneration by Dichotomously Regulating Quiescence of Stem and Progenitor Cells SO CELL LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; TRANSFER-RNA HALVES; SELF-RENEWAL; GENE-EXPRESSION; CORD BLOOD; PROLIFERATION; MAINTENANCE; STRESS; IDENTIFICATION; EXPANSION AB Regulation of stem and progenitor cell populations is critical in the development, maintenance, and regeneration of tissues. Here, we define a novelmechanism by which a niche-secreted RNase, angiogenin (ANG), distinctively alters the functional characteristics of primitive hematopoietic stem/progenitor cells (HSPCs) compared with lineage-committed myeloid-restricted progenitor (MyePro) cells. Specifically, ANG reduces the proliferative capacity of HSPC while simultaneously increasing proliferation of MyePro cells. Mechanistically, ANG induces cell-type-specific RNA-processing events: tRNAderived stress-induced small RNA (tiRNA) generation in HSPCs and rRNA induction in MyePro cells, leading to respective reduction andincrease inprotein synthesis. Recombinant ANG protein improves survival of irradiated animals and enhances hematopoietic regeneration of mouse and human HSPCs in transplantation. Thus, ANG plays a non-cell-autonomous role in regulation of hematopoiesis by simultaneously preserving HSPC stemness and promoting MyePro proliferation. These cell-type-specific functions of ANG suggest considerable therapeutic potential. C1 [Goncalves, Kevin A.; Li, Shuping; Hu, Miaofen G.; Yang, Hailing; Hu, Guo-fu] Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. [Goncalves, Kevin A.; Yang, Hailing; Hu, Guo-fu] Tufts Univ, Sackler Sch Grad Biomed Sci, Grad Program Cellular & Mol Physiol, Boston, MA 02111 USA. [Silberstein, Lev; Severe, Nicolas; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02445 USA. [Silberstein, Lev; Severe, Nicolas; Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Silberstein, Lev; Severe, Nicolas; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP Hu, GF (reprint author), Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA.; Hu, GF (reprint author), Tufts Univ, Sackler Sch Grad Biomed Sci, Grad Program Cellular & Mol Physiol, Boston, MA 02111 USA.; Scadden, DT (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02445 USA.; Scadden, DT (reprint author), Harvard Stem Cell Inst, Cambridge, MA 02138 USA.; Scadden, DT (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. EM david_scadden@harvard.edu; guo-fu.hu@tufts.edu FU NIH [F31HL128127, R01DK107784, R01HL096372, R01CA105241, R01NS065237]; Sackler Dean's Fellow award; Sackler Families Collaborative Cancer Biology award; Leukemia & Lymphoma Research UK/Leukemia & Lymphoma Society fellowships; NSFC [81272674]; DoD [W81XWH-15-1-0207] FX We thank Kathryn Folz-Donahue, Steven Kwok, Allen Parmalee, Laura Prickett-Rice, and Meredith Weglarz for assistance with cell sorting and Dr. Alenka Lovy for assistance with microscopy. Aged WT mice were kindly provided by NIH/NIA, and Osx and Ocn cDNA were gifts kindly provided by Dr. Deepak Balani and Dr. Henry Kronenberg. This work was supported by NIH fellowship F31HL128127 (to K.A.G.), a Sackler Dean's Fellow award (to K.A.G.), a Sackler Families Collaborative Cancer Biology award (to K.A.G. and G.H.), Leukemia & Lymphoma Research UK/Leukemia & Lymphoma Society fellowships (to L.S.), NSFC grant #81272674 (to S.L.), NIH grants R01DK107784 and R01HL096372 (to D.T.S.), DoD Award W81XWH-15-1-0207 (to G.H.), and NIH grants R01CA105241 and R01NS065237 (to G.H.). D.T.S. is a consultant and stockholder for Magenta Therapeutics and Fate Therapeutics and a consultant for Bone Therapeutics, Teva Pharmaceutical Industries, Dr. Reddy's Laboratories, and Apotex. G.H. is a consultant and stockholder of Fuyuan Biopharmaceuticals and Karma Pharmaceuticals. NR 45 TC 4 Z9 4 U1 9 U2 11 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 AUG 11 PY 2016 VL 166 IS 4 BP 894 EP 906 DI 10.1016/j.cell.2016.06.042 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DU5NO UT WOS:000382258700013 PM 27518564 ER PT J AU Yagyu, S Iehara, T Tanaka, S Gotoh, T Misawa-Furihata, A Sugimoto, T London, WB Hogarty, MD Teramukai, S Nakagawara, A Hiyama, E Maris, JM Hosoi, H AF Yagyu, Shigeki Iehara, Tomoko Tanaka, Shiro Gotoh, Takahiro Misawa-Furihata, Akiko Sugimoto, Tohru London, Wendy B. Hogarty, Michael D. Teramukai, Satoshi Nakagawara, Akira Hiyama, Eiso Maris, John M. Hosoi, Hajime TI Serum-Based Quantification of MYCN Gene Amplification in Young Patients with Neuroblastoma: Potential Utility as a Surrogate Biomarker for Neuroblastoma SO PLOS ONE LA English DT Article ID CHILDRENS-ONCOLOGY-GROUP; LOCALIZED NEUROBLASTOMA; SPONTANEOUS REGRESSION; CANCER PATIENTS; RISK GROUP; PROGNOSIS; INFANTS; DNA; STRATIFICATION; CLASSIFICATION AB We previously developed a method for determining MYCN gene amplification status using cell-free DNA fragments released from cancer cells into the blood of patients with neuroblastoma (NB). Here, we analyzed the relationship between MYCN amplification (MNA) status and neuroblastoma prognosis. We screened serum samples from 151 patients with NB for MNA, using real-time quantitative PCR, and compared the results with MYCN status determined using paired tumor samples. We additionally investigated whether MNA status correlates with patient survival. When a cut-off value of 5 was used, serum-based MNA analysis was found to show good sensitivity (86%) and very high specificity (95%). The sensitivities for stage 1 and 2 might be acceptable, even though it is not as good as for stage 3 and 4 (67% for stage 1 and 2, 92% for stage 3, and 87% for stage 4). MNA status correlated with overall survival in our cohort of 82 patients, with survival data available (p < 0.01). The hazard ratio of MNA status was 4.98 in patients diagnosed at less than 18 months of age (95% confidence interval, 1.00-24.78), and 1.41 (95% confidence interval, 0.63-3.14) for those diagnosed at 18 months of age or older. Serum-based MNA analysis is rapid and non-invasive compared with tumor-based MNA analysis, and has potential to predict tumor MNA status. There is still a room to improve the sensitivity of the test for tumors of stages 1 and 2, nonetheless this assay might help to determine therapeutic strategies prior to tumor biopsy, especially for patients with a life-threatening condition, as well as for patients of less than 18 months of age whose risk-grouping and treatment allocation depends on their MNA status. C1 [Yagyu, Shigeki; Iehara, Tomoko; Gotoh, Takahiro; Misawa-Furihata, Akiko; Sugimoto, Tohru; Hosoi, Hajime] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Dept Pediat, Kyoto, Japan. [Tanaka, Shiro] Kyoto Univ, Grad Sch Med & Publ Hlth, Dept Pharmacoepidemiol, Kyoto, Japan. [London, Wendy B.] Harvard Med Sch, Dana Farber Canc Inst, Childrens Hosp Boston, Div Hematol Oncol, Boston, MA USA. [Hogarty, Michael D.; Maris, John M.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. [Hogarty, Michael D.; Maris, John M.] Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA. [Hogarty, Michael D.; Maris, John M.] Univ Penn, Philadelphia, PA 19104 USA. [Teramukai, Satoshi] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Dept Biostat, Kyoto, Japan. [Nakagawara, Akira] Chiba Canc Ctr, Div Biochem & Innovat Canc Therapeut, Chiba, Japan. [Nakagawara, Akira] Saga Med Canc KOSEIKAN, Saga, Japan. [Hiyama, Eiso] Hiroshima Univ, Hiroshima Univ Hosp, Nat Sci Ctr Basic Res & Dev, Dept Pediat Surg, Hiroshima, Japan. RP Hosoi, H (reprint author), Kyoto Prefectural Univ Med, Grad Sch Med Sci, Dept Pediat, Kyoto, Japan. EM hhosoi@koto.kpu-m.ac.jp FU Japan Society for the Promotion of Science (JSPS) KAKENHI [25253095]; Practical Research for Innovative Cancer Control from Japan Agency for Medical Research and development (AMED); Kyoto-Funding for Innovation in Health-related RD Fields Grant [88]; Adaptable and Seamless Technology Transfer Program through Target-driven RD [AS221Z03404F] FX This work was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI, Grant Number 25253095, (https://www.jsps.go.jp/english/e-grants/); the Practical Research for Innovative Cancer Control from Japan Agency for Medical Research and development (AMED), (http://www.amed.go.jp/en/); Kyoto-Funding for Innovation in Health-related R&D Fields Grant Number 88, (http://www.astem.or.jp/english/); Adaptable and Seamless Technology Transfer Program through Target-driven R&D, Grant Number AS221Z03404F, (http://www.jst.go.jp/tt/EN/univ-ip/a-step.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 0 Z9 0 U1 0 U2 0 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 AUG 11 PY 2016 VL 11 IS 8 AR e0161039 DI 10.1371/journal.pone.0161039 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DT3KY UT WOS:000381381100114 PM 27513929 ER PT J AU Batalha, VL Ferreira, DG Coelho, JE Valadas, JS Gomes, R Temido-Ferreira, M Shmidt, T Baqi, Y Buee, L Muller, CE Hamdane, M Outeiro, TF Bader, M Meijsing, SH Sadri-Vakili, G Blum, D Lopes, LV AF Batalha, Vania L. Ferreira, Diana G. Coelho, Joana E. Valadas, Jorge S. Gomes, Rui Temido-Ferreira, Mariana Shmidt, Tatiana Baqi, Younis Buee, Luc Mueller, Christa E. Hamdane, Malika Outeiro, Tiago F. Bader, Michael Meijsing, Sebastiaan H. Sadri-Vakili, Ghazaleh Blum, David Lopes, Luisa V. TI The caffeine-binding adenosine A(2A) receptor induces age-like HPA-axis dysfunction by targeting glucocorticoid receptor function SO SCIENTIFIC REPORTS LA English DT Article ID LONG-TERM-POTENTIATION; PROTEIN-KINASE-A; ALZHEIMERS-DISEASE; GENE-EXPRESSION; SYNAPTIC-TRANSMISSION; SALIVARY CORTISOL; RESPONSE ELEMENTS; MEMORY DEFICITS; TAU PATHOLOGY; UP-REGULATION AB Caffeine is associated with procognitive effects in humans by counteracting overactivation of the adenosine A(2A) receptor (A(2A)R), which is upregulated in the human forebrain of aged and Alzheimer's disease (AD) patients. We have previously shown that an anti-A(2A)R therapy reverts age-like memory deficits, by reestablishment of the hypothalamic-pituitary-adrenal (HPA) axis feedback and corticosterone circadian levels. These observations suggest that A(2A)R over-activation and glucocorticoid dysfunction are key events in age-related hippocampal deficits; but their direct connection has never been explored. We now show that inducing A(2A)R overexpression in an aging-like profile is sufficient to trigger HPA-axis dysfunction, namely loss of plasmatic corticosterone circadian oscillation, and promotes reduction of GR hippocampal levels. The synaptic plasticity and memory deficits triggered by finally, we demonstrate that A(2A)R act on GR nuclear translocation and GR-dependent transcriptional regulation. We provide the first demonstration that A(2A)R is a major regulator of GR function and that this functional interconnection may be a trigger to age-related memory deficits. This supports the idea that the procognitive effects of A(2A)R antagonists, namely caffeine, on Alzheimer's and age-related cognitive impairments may rely on its ability to modulate GR actions. C1 [Batalha, Vania L.; Ferreira, Diana G.; Coelho, Joana E.; Valadas, Jorge S.; Gomes, Rui; Temido-Ferreira, Mariana; Lopes, Luisa V.] Univ Lisbon, Fac Med Lisboa, Inst Mol Med, Lisbon, Portugal. [Batalha, Vania L.; Meijsing, Sebastiaan H.] Max Planck Inst Mol Genet, Berlin, Germany. [Ferreira, Diana G.; Outeiro, Tiago F.] Univ Med Ctr Goettingen, Dept NeuroDegenerat & Restorat Res, Waldweg 33, D-37073 Gottingen, Germany. [Ferreira, Diana G.] Univ Porto, Fac Med Porto, Inst Farmacol & Terapeut, Oporto, Portugal. [Gomes, Rui] Univ Lisbon, Fac Ciencias Lisboa, Lisbon, Portugal. [Shmidt, Tatiana] Max Delbrck Ctr Mol Med MDC, Berlin, Germany. [Baqi, Younis; Mueller, Christa E.] Univ Bonn, PharmaCtr Bonn, Inst Pharmazeut, Pharmazeut Chem 1, Bonn, Germany. [Baqi, Younis] Sultan Qaboos Univ, Fac Sci, Dept Chem, Muscat, Oman. [Buee, Luc; Hamdane, Malika; Blum, David] Univ Lille, CHU Lille, INSERM, Alzheimer & Tauopathies,UMR S 1172, Lille, France. [Outeiro, Tiago F.] Max Planck Inst Expt Med, Gottingen, Germany. [Outeiro, Tiago F.] CEDOC, Ctr Estudos Doencas Cronicas, Lisbon, Portugal. [Bader, Michael] Charite, Berlin, Germany. [Bader, Michael] Univ Lubeck, Inst Biol, Lubeck, Germany. [Sadri-Vakili, Ghazaleh] Massachusetts Gen Hosp, MassGeneral Inst Neurodegenerat Dis, Boston, MA USA. [Valadas, Jorge S.] VIB, Ctr Biol Dis, Leuven, Belgium. [Valadas, Jorge S.] Katholieke Univ Leuven, Ctr Human Genet, Leuven, Belgium. [Valadas, Jorge S.] Leuven Res Inst Neurosci & Dis LIND, Leuven, Belgium. RP Lopes, LV (reprint author), Univ Lisbon, Fac Med Lisboa, Inst Mol Med, Lisbon, Portugal.; Blum, D (reprint author), Univ Lille, CHU Lille, INSERM, Alzheimer & Tauopathies,UMR S 1172, Lille, France. EM david.blum@inserm.fr; lvlopes@medicina.ulisboa.pt RI Gomes, Rui /M-1803-2015; Blum, David/E-9901-2016; Muller, Christa/C-7748-2014; OI Gomes, Rui /0000-0002-7242-6540; Blum, David/0000-0001-5691-431X; Muller, Christa/0000-0002-0013-6624; Baqi, Younis/0000-0002-9659-8419 FU Fundacao para a Ciencia e Tecnologia [PTDC-099853/2009]; EMBO fellowship (Harvard Medical School-GSV lab-exchange period); DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain; LabEx (excellence laboratory) DISTALZ (Development of Innovative Strategies for a Transdisciplinary approach to Alzheimer's disease); Inserm; CNRS; Universite Lille 2; Region Nord/Pas-de-Calais; DN2M; ANR (ADORATAU); FUI MEDIALZ; LECMA/Alzheimer Forschung Initiative (AFI); PHC FCT/Pessoa program; international exchange program (AAP Internationalisation / LIA) - University of Lille FX The authors acknowledge J. Baiao for technical assistance in the animal house and C. Batalha for the figures layout. VLB and DGF were supported by a grant from Fundacao para a Ciencia e Tecnologia and an EMBO fellowship (Harvard Medical School-GSV lab-exchange period); LVL is an Investigator FCT, funded by Fundacao para a Ciencia e Tecnologia (PTDC-099853/2009). TFO is supported by the DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain. MH, LB and DB thank the following supports: LabEx (excellence laboratory) DISTALZ (Development of Innovative Strategies for a Transdisciplinary approach to Alzheimer's disease), Inserm, CNRS, Universite Lille 2, Region Nord/Pas-de-Calais, DN2M, ANR (ADORATAU) and FUI MEDIALZ. DB, CEM and YB are grateful for support by the LECMA/Alzheimer Forschung Initiative (AFI). DB and LVL were recipients of PHC FCT/Pessoa program and are currently recipients of an international exchange program (AAP Internationalisation / LIA) funded by the University of Lille. NR 68 TC 0 Z9 0 U1 6 U2 12 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 AUG 11 PY 2016 VL 6 AR 31493 DI 10.1038/srep31493 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DT0QW UT WOS:000381189100001 PM 27510168 ER PT J AU Kiesewetter, I Schulz, C Bausewein, C Fountain, R Schmitz, A AF Kiesewetter, Isabel Schulz, Christian Bausewein, Claudia Fountain, Rita Schmitz, Andrea TI Patients' perception of types of errors in palliative care - results from a qualitative interview study SO BMC PALLIATIVE CARE LA English DT Article DE Error; Medical error; Palliative care; Patient's perspective ID MEDICAL ERRORS; ADVERSE EVENTS; HEALTH-CARE; HOSPITALIZED-PATIENTS; SAFETY; PHYSICIANS; ATTITUDES; CRITERIA AB Background: Medical errors have been recognized as a relevant public health concern and research efforts to improve patient safety have increased. In palliative care, however, studies on errors are rare and mainly focus on quantitative measures. We aimed to explore how palliative care patients perceive and think about errors in palliative care and to generate an understanding of patients' perception of errors in that specialty. Methods: A semistructured qualitative interview study was conducted with patients who had received at least 1 week of palliative care in an inpatient or outpatient setting. All interviews were transcribed verbatim and analysed according to qualitative content analysis. Results: Twelve patients from two centers were interviewed (7 women, median age 63.5 years, range 22-90 years). Eleven patients suffered from a malignancy. Days in palliative care ranged from 10 to 180 days (median 28 days). 96 categories emerged which were summed up under 11 umbrella terms definition, difference, type, cause, consequence, meaning, recognition, handling, prevention, person causing and affected person. A deductive model was developed assigning umbrella terms to error-theory-based factor levels (definition, type and process-related factors). 23 categories for type of error were identified, including 12 categories that can be considered as palliative care specific. On the level of process-related factors 3 palliative care specific categories emerged (recognition, meaning and consequence of errors). Conclusion: From the patients' perspective, there are some aspects of errors that could be considered as specific to palliative care. As the results of our study suggest, these palliative care-specific aspects seem to be very important from the patients' point of view and should receive further investigation. Moreover, the findings of this study can serve as a guide to further assess single aspects or categories of errors in palliative care in future research. C1 [Kiesewetter, Isabel] Univ Munich, Dept Anaesthesiol, Munich Univ Hosp, Munich, Germany. [Kiesewetter, Isabel; Bausewein, Claudia] Univ Munich, Dept Palliat Med, Munich Univ Hosp, Munich, Germany. [Schulz, Christian] Kings Coll London, Inst Psychiat Psychol & Neurosci, Maudsley Training Programme, London, England. [Fountain, Rita] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Schmitz, Andrea] Heinrich Heine Univ Hosp Dsseldorf, Interdisciplinary Ctr Palliat Med, Dusseldorf, Germany. [Schmitz, Andrea] LVR Clin Psychiat Psychosomat & Psychotherapy Chi, Viersen, Germany. RP Kiesewetter, I (reprint author), Univ Munich, Dept Anaesthesiol, Munich Univ Hosp, Munich, Germany.; Kiesewetter, I (reprint author), Univ Munich, Dept Palliat Med, Munich Univ Hosp, Munich, Germany. EM Isabel.Kiesewetter@med.uni-muenchen.de FU Dr. Werner Jackstadt Foundation FX Many thanks to the Dr. Werner Jackstadt Foundation, that supported the first author in her master studies of which the present project was part of. NR 34 TC 0 Z9 0 U1 5 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-684X J9 BMC PALLIAT CARE JI BMC Palliat. Care PD AUG 11 PY 2016 VL 15 AR 75 DI 10.1186/s12904-016-0141-4 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA DT6DB UT WOS:000381572100001 PM 27515997 ER PT J AU Nierhaus, T Pach, D Huang, WJ Long, XY Napadow, V Roll, S Liang, FR Pleger, B Villringer, A Witt, CM AF Nierhaus, Till Pach, Daniel Huang, Wenjing Long, Xiangyu Napadow, Vitaly Roll, Stephanie Liang, Fanrong Pleger, Burkhard Villringer, Arno Witt, Claudia M. TI Difficulties Choosing Control Points in Acupuncture Research. Response: Commentary: Differential Cerebral Response, Measured with Both an EEG and fMRI, to Somatosensory Stimulation of a Single Acupuncture Point vs. Two Non-Acupuncture Points SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Editorial Material DE somatosensory stimulation; functional magnetic resonance imaging (fMRI); electroencephalography (EEG); acupuncture; background rhythm; functional connectivity C1 [Nierhaus, Till; Villringer, Arno] Charite Univ Med Berlin, Mind Brain Inst, Berlin Sch Mind & Brain, Berlin, Germany. [Nierhaus, Till; Villringer, Arno] Humboldt Univ, Berlin, Germany. [Nierhaus, Till; Long, Xiangyu; Pleger, Burkhard; Villringer, Arno] Max Planck Inst Human Cognit & Brain Sci, Dept Neurol, Leipzig, Germany. [Pach, Daniel; Huang, Wenjing; Roll, Stephanie; Witt, Claudia M.] Charite Univ Med Berlin, Inst Social Med Epidemiol & Hlth Econ, Berlin, Germany. [Huang, Wenjing; Liang, Fanrong] Chengdu Univ Tradit Chinese Med, Acupuncture Moxibust & Tuina Sch, Chengdu, Peoples R China. [Napadow, Vitaly] Harvard Med Sch, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [Napadow, Vitaly] Logan Univ, Dept Radiol, Chesterfield, MO USA. [Witt, Claudia M.] Univ Zurich Hosp, Inst Complementary & Integrat Med, Zurich, Switzerland. RP Nierhaus, T (reprint author), Charite Univ Med Berlin, Mind Brain Inst, Berlin Sch Mind & Brain, Berlin, Germany.; Nierhaus, T (reprint author), Humboldt Univ, Berlin, Germany.; Nierhaus, T (reprint author), Max Planck Inst Human Cognit & Brain Sci, Dept Neurol, Leipzig, Germany. EM till.nierhaus@fu-berlin.de NR 14 TC 1 Z9 1 U1 7 U2 7 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1662-5161 J9 FRONT HUM NEUROSCI JI Front. Hum. Neurosci. PD AUG 11 PY 2016 VL 10 AR 404 DI 10.3389/fnhum.2016.00404 PG 3 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA DT2ZZ UT WOS:000381351600001 PM 27562659 ER PT J AU Roemer, MGM Advani, RH Ligon, AH Natkunam, Y Redd, RA Homer, H Connelly, CF Sun, HH Daadi, SE Freeman, GJ Armand, P Chapuy, B de Jong, D Hoppe, RT Neuberg, DS Rodig, SJ Shipp, MA AF Roemer, Margaretha G. M. Advani, Ranjana H. Ligon, Azra H. Natkunam, Yasodha Redd, Robert A. Homer, Heather Connelly, Courtney F. Sun, Heather H. Daadi, Sarah E. Freeman, Gordon J. Armand, Philippe Chapuy, Bjoern de Jong, Daphne Hoppe, Richard T. Neuberg, Donna S. Rodig, Scott J. Shipp, Margaret A. TI PD-L1 and PD-L2 Genetic Alterations Define Classical Hodgkin Lymphoma and Predict Outcome SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID B-CELL LYMPHOMA; REED-STERNBERG CELLS; PHASE-III TRIAL; STANFORD-V; EXPRESSION; RADIOTHERAPY; IMBALANCES; INTERGROUP; RECURRENT; BLOCKADE AB Purpose Classical Hodgkin lymphomas (cHLs) include small numbers of malignant Reed-Sternberg cells within an extensive but ineffective inflammatory/immune cell infiltrate. In cHL, chromosome 9p24.1/PD-L1/PD-L2 alterations increase the abundance of the PD-1 ligands, PD-L1 and PD-L2, and their further induction through Janus kinase 2-signal transducers and activators of transcription signaling. The unique composition of cHL limits its analysis with high-throughput genomic assays. Therefore, the precise incidence, nature, and prognostic significance of PD-L1/PD-L2 alterations in cHL remain undefined. Methods We used a fluorescent in situ hybridization assay to evaluate CD274/PD-L1 and PDCD1LG2/PD-L2 alterations in 108 biopsy specimens from patients with newly diagnosed cHL who were treated with the Stanford V regimen and had long-term follow-up. In each case, the frequency and magnitude of 9p24.1 alterations-polysomy, copy gain, and amplification-were determined, and the expression of PD-L1 and PD-L2 was evaluated by immunohistochemistry. We also assessed the association of 9p24.1 alterations with clinical parameters, which included stage (early stage I/II favorable risk, early stage unfavorable risk, advanced stage [AS] III/IV) and progression-free survival (PFS). Results Ninety-seven percent of all evaluated cHLs had concordant alterations of the PD-L1 and PD-L2 loci (polysomy, 5% [five of 108]; copy gain, 56% [61 of 108]; amplification, 36% [39 of 108]). There was an association between PD-L1 protein expression and relative genetic alterations in this series. PFS was significantly shorter for patients with 9p24.1 amplification, and the incidence of 9p24.1 amplification was increased in patients with AS cHL. Conclusion PD-L1/PD-L2 alterations are a defining feature of cHL. Amplification of 9p24.1 is more common in patients with AS disease and associated with shorter PFS in this series. Further analyses of 9p24.1 alterations in patients treated with standard cHL induction regimens or checkpoint blockade are warranted. (C) 2016 by American Society of Clinical Oncology C1 [Roemer, Margaretha G. M.; Redd, Robert A.; Homer, Heather; Connelly, Courtney F.; Freeman, Gordon J.; Armand, Philippe; Chapuy, Bjoern; Neuberg, Donna S.; Shipp, Margaret A.] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. [Ligon, Azra H.; Homer, Heather; Rodig, Scott J.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Roemer, Margaretha G. M.; de Jong, Daphne] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands. [Advani, Ranjana H.; Natkunam, Yasodha; Daadi, Sarah E.; Hoppe, Richard T.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. RP Shipp, MA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM margaret_shipp@dfci.harvard.edu FU National Institutes of Health [R01 CA161026]; Miller Family Fund FX Supported by National Institutes of Health Grant No. R01 CA161026 and the Miller Family Fund (M.A.S.). NR 26 TC 23 Z9 23 U1 4 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 10 PY 2016 VL 34 IS 23 BP 2690 EP + DI 10.1200/JCO.2016.66.4482 PG 15 WC Oncology SC Oncology GA DU8MF UT WOS:000382467000004 PM 27069084 ER PT J AU Lesokhin, AM Ansell, SM Armand, P Scott, EC Halwani, A Gutierrez, M Millenson, MM Cohen, AD Schuster, SJ Lebovic, D Dhodapkar, M Avigan, D Chapuy, B Ligon, AH Freeman, GJ Rodig, SJ Cattry, D Zhu, LL Grosso, JF Garelik, MBB Shipp, MA Borrello, I Timmerman, J AF Lesokhin, Alexander M. Ansell, Stephen M. Armand, Philippe Scott, Emma C. Halwani, Ahmad Gutierrez, Martin Millenson, Michael M. Cohen, Adam D. Schuster, Stephen J. Lebovic, Daniel Dhodapkar, Madhav Avigan, David Chapuy, Bjoern Ligon, Azra H. Freeman, Gordon J. Rodig, Scott J. Cattry, Deepika Zhu, Lili Grosso, Joseph F. Garelik, M. Brigid Bradley Shipp, Margaret A. Borrello, Ivan Timmerman, John TI Nivolumab in Patients With Relapsed or Refractory Hematologic Malignancy: Preliminary Results of a Phase Ib Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID B-CELL LYMPHOMA; RESPONSE CRITERIA; ADVANCED MELANOMA; MULTIPLE-MYELOMA; B7-H1 PD-L1; EXPRESSION; CANCER; BLOCKADE; IPILIMUMAB; ANTIBODY AB Purpose Cancer cells can exploit the programmed death-1 (PD-1) immune checkpoint pathway to avoid immune surveillance by modulating T-lymphocyte activity. In part, this may occur through overexpression of PD-1 and PD-1 pathway ligands (PD-L1 and PD-L2) in the tumor microenvironment. PD-1 blockade has produced significant antitumor activity in solid tumors, and similar evidence has emerged in hematologic malignancies. Methods In this phase I, open-label, dose-escalation, cohort-expansion study, patients with relapsed or refractory B-cell lymphoma, T-cell lymphoma, and multiple myeloma received the anti-PD-1 monoclonal antibody nivolumab at doses of 1 or 3 mg/kg every 2 weeks. This study aimed to evaluate the safety and efficacy of nivolumab and to assess PD-L1/PD-L2 locus integrity and protein expression. Results Eighty-one patients were treated (follicular lymphoma, n = 10; diffuse large B-cell lymphoma, n = 11; other B-cell lymphomas, n = 10; mycosis fungoides, n = 13; peripheral T-cell lymphoma, n = 5; other T-cell lymphomas, n = 5; multiple myeloma, n = 27). Patients had received a median of three (range, one to 12) prior systemic treatments. Drug-related adverse events occurred in 51 (63%) patients, and most were grade 1 or 2. Objective response rates were 40%, 36%, 15%, and 40% among patients with follicular lymphoma, diffuse large B-cell lymphoma, mycosis fungoides, and peripheral T-cell lymphoma, respectively. Median time of follow-up observation was 66.6 weeks (range, 1.6 to 132.0+ weeks). Durations of response in individual patients ranged from 6.0 to 81.6+ weeks. Conclusion Nivolumab was well tolerated and exhibited antitumor activity in extensively pretreated patients with relapsed or refractory B-and T-cell lymphomas. Additional studies of nivolumab in these diseases are ongoing. (C) 2016 by American Society of Clinical Oncology C1 [Lesokhin, Alexander M.; Cattry, Deepika] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA. [Lesokhin, Alexander M.] Weill Cornell Med Coll, New York, NY USA. [Ansell, Stephen M.] Mayo Clin, Rochester, MN USA. [Armand, Philippe; Chapuy, Bjoern; Freeman, Gordon J.; Rodig, Scott J.; Shipp, Margaret A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Avigan, David] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Ligon, Azra H.; Rodig, Scott J.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Scott, Emma C.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Halwani, Ahmad] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Gutierrez, Martin] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Zhu, Lili; Grosso, Joseph F.; Garelik, M. Brigid Bradley] Bristol Myers Squibb, Princeton, NJ USA. [Millenson, Michael M.] Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. [Cohen, Adam D.; Schuster, Stephen J.] Univ Penn, Philadelphia, PA 19104 USA. [Lebovic, Daniel] Univ Michigan, Ann Arbor, MI 48109 USA. [Dhodapkar, Madhav] Yale Canc Ctr, New Haven, CT USA. [Borrello, Ivan] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Timmerman, John] Univ Calif Los Angeles, Los Angeles, CA USA. RP Lesokhin, AM (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA. EM lesokhia@mskcc.org FU National Institutes of Health [U54CA163125, P01AI056299, R01CA161026]; Miller Fund FX Supported by Bristol-Myers Squibb, grants from the National Institutes of Health (U54CA163125 and P01AI056299 to G.J.F. and R01CA161026 to M.A.S.), and a grant from the Miller Fund (to M.A.S.). NR 25 TC 35 Z9 36 U1 12 U2 13 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 AUG 10 PY 2016 VL 34 IS 23 BP 2698 EP + DI 10.1200/JCO.2015.65.9789 PG 10 WC Oncology SC Oncology GA DU8MF UT WOS:000382467000005 PM 27269947 ER PT J AU Preston, MA Batista, JL Wilson, KM Carlsson, SV Gerke, T Sjoberg, DD Dahl, DM Sesso, HD Feldman, AS Gann, PH Kibel, AS Vickers, AJ Mucci, LA AF Preston, Mark A. Batista, Julie L. Wilson, Kathryn M. Carlsson, Sigrid V. Gerke, Travis Sjoberg, Daniel D. Dahl, Douglas M. Sesso, Howard D. Feldman, Adam S. Gann, Peter H. Kibel, Adam S. Vickers, Andrew J. Mucci, Lorelei A. TI Baseline Prostate-Specific Antigen Levels in Midlife Predict Lethal Prostate Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LONG-TERM RISK; UNITED-STATES; BLACK-MEN; FOLLOW-UP; AGE; MORTALITY; OVERDIAGNOSIS; WHITE; OLD; PSA AB Purpose Prostate-specific antigen (PSA) level in midlife predicted future prostate cancer (PCa) mortality in an unscreened Swedish population. Our purpose was to determine if a baseline PSA level during midlife predicts lethal PCa in a US population with opportunistic screening. Materials and Methods We conducted a nested case-control study among men age 40 to 59 years who gave blood before random assignment in the Physicians' Health Study, a randomized, placebo-controlled trial of aspirin and beta-carotene among 22,071 US male physicians initiated in 1982 and then transitioned into a prospective cohort with 30 years of follow-up. Baseline PSA levels were available for 234 patients with PCa and 711 age-matched controls. Seventy-one participants who developed lethal PCa were rematched to 213 controls. Conditional logistic regression was used to estimate odds ratios and the area under the receiver operating characteristic curve, with 95% CIs, of the association between baseline PSA and risk of lethal PCa. Results Median PSA among controls was 0.68, 0.88, and 0.96 ng/mL for men age 40 to 49, 50 to 54, and 55 to 59 years, respectively. Risk of lethal PCa was strongly associated with baseline PSA in midlife: odds ratios (95% CIs) comparing PSA in the >90th percentile versus less than or equal to median were 8.7 (1.0 to 78.2) at 40 to 49 years, 12.6 (1.4 to 110.4) at 50 to 54 years, and 6.9 (2.5 to 19.1) at 55 to 59 years. A total of 82%, 71%, and 86% of lethal cases occurred in men with PSA above the median at ages 40 to 49, 50 to 54, and 55 to 59 years, respectively. Conclusion PSA levels in midlife strongly predict future lethal PCa in a US cohort subject to opportunistic screening. Risk-stratified screening on the basis of midlife PSA should be considered in men age 45 to 59 years. (C) 2016 by American Society of Clinical Oncology C1 [Preston, Mark A.; Batista, Julie L.; Sesso, Howard D.; Kibel, Adam S.] Brigham & Womens Hosp, 45 Francis St, Boston, MA 02115 USA. [Batista, Julie L.; Wilson, Kathryn M.; Gerke, Travis; Sesso, Howard D.; Mucci, Lorelei A.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA. [Batista, Julie L.] Harvard Med Sch, Boston, MA USA. [Dahl, Douglas M.; Feldman, Adam S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Carlsson, Sigrid V.; Sjoberg, Daniel D.; Vickers, Andrew J.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Carlsson, Sigrid V.] Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden. [Gann, Peter H.] Univ Illinois, Chicago, IL USA. RP Preston, MA (reprint author), Brigham & Womens Hosp, 45 Francis St, Boston, MA 02115 USA. EM mpreston@bwh.harvard.edu FU National Institutes of Health [CA-097193, CA-34944, CA-40360, HL-26490, HL-34595]; Department of Defense Prostate Cancer Research Program [W81XWH-12-1-0072]; Dana-Farber Cancer Institute Mazzone Awards Program; Prostate Cancer Foundation Young Investigator Award; American Urological Association Urology Care Foundation Scholar; National Cancer Institute [R33 CA127768-02, P50-CA92629, P50-CA090381]; Swedish Cancer Society [3455]; Fundacion Federico; Sidney Kimmel Center for Prostate and Urologic Cancers; Prostate Cancer Foundation; National Cancer Institute made to Memorial Sloan Kettering Cancer Center [P30-CA008748] FX The Physicians' Health Study was supported by the National Institutes of Health Grants No. CA-097193, CA-34944, CA-40360, HL-26490, and HL-34595. This work was also supported by the Department of Defense Prostate Cancer Research Program Grant No. W81XWH-12-1-0072 (J.L.B.), Dana-Farber Cancer Institute Mazzone Awards Program (J.L.B. and M.A.P.), and the Prostate Cancer Foundation Young Investigator Award (L.A.M.); M.A.P. is an American Urological Association Urology Care Foundation Scholar. Additional funding support provided from the National Cancer Institute Grants No. R33 CA127768-02, P50-CA92629, and P50-CA090381; Swedish Cancer Society Grant No. 3455; Fundacion Federico; the Sidney Kimmel Center for Prostate and Urologic Cancers; David H. Koch through the Prostate Cancer Foundation; and a Cancer Center Support Grant from the National Cancer Institute made to Memorial Sloan Kettering Cancer Center Grant No. P30-CA008748 (S.C., D.S., and A.V.; PI: Craig B. Thompson). NR 28 TC 3 Z9 3 U1 5 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 AUG 10 PY 2016 VL 34 IS 23 BP 2705 EP + DI 10.1200/JCO.2016.66.7527 PG 9 WC Oncology SC Oncology GA DU8MF UT WOS:000382467000006 PM 27298404 ER PT J AU Frisina, RD Wheeler, HE Fossa, SD Kerns, SL Fung, C Sesso, HD Monahan, PO Feldman, DR Hamilton, R Vaughn, DJ Beard, CJ Budnick, A Johnson, EM Ardeshir-Rouhani-Fard, S Einhorn, LH Lipshultz, SE Dolan, ME Travis, LB AF Frisina, Robert D. Wheeler, Heather E. Fossa, Sophie D. Kerns, Sarah L. Fung, Chunkit Sesso, Howard D. Monahan, Patrick O. Feldman, Darren R. Hamilton, Robert Vaughn, David J. Beard, Clair J. Budnick, Amy Johnson, Eileen M. Ardeshir-Rouhani-Fard, Shirin Einhorn, Lawrence H. Lipshultz, Steven E. Dolan, M. Eileen Travis, Lois B. TI Comprehensive Audiometric Analysis of Hearing Impairment and Tinnitus After Cisplatin-Based Chemotherapy in Survivors of Adult-Onset Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HIGH-FREQUENCY AUDIOMETRY; TERM-FOLLOW-UP; TESTICULAR CANCER; INDUCED OTOTOXICITY; PLATINUM CHEMOTHERAPY; RISK-FACTORS; CHILDREN; EPIDEMIOLOGY; POPULATION; PRESBYCUSIS AB Purpose Cisplatin is widely used but highly ototoxic. Effects of cumulative cisplatin dose on hearing loss have not been comprehensively evaluated in survivors of adult-onset cancer. Patients and Methods Comprehensive audiological measures were conducted on 488 North American male germ cell tumor (GCT) survivors in relation to cumulative cisplatin dose, including audiograms (0.25 to 12 kHz), tests of middle ear function, and tinnitus. American Speech-Language-Hearing Association criteria defined hearing loss severity. The geometric mean of hearing thresholds (0.25 to 12 kHz) summarized overall hearing status consistent with audiometric guidelines. Patients were sorted into quartiles of hearing thresholds of age-and sex-matched controls. Results Increasing cumulative cisplatin dose (median, 400 mg/m(2); range, 200 to 800 mg/m(2)) was significantly related to hearing loss at 4, 6, 8, 10, and 12 kHz (P trends, .021 to < .001): every 100 mg/m(2) increase resulted in a 3.2-dB impairment in age-adjusted overall hearing threshold (4 to 12 kHz; P < .001). Cumulative cisplatin doses > 300 mg/m(2) were associated with greater American Speech-Language-Hearing Association-defined hearing loss severity (odds ratio, 1.59; P = .0066) and worse normative-matched quartiles (odds ratio, 1.33; P = .093) compared with smaller doses. Almost one in five (18%) patients had severe to profound hearing loss. Tinnitus (40% patients) was significantly correlated with reduced hearing at each frequency (P < .001). Noise-induced damage (10% patients) was unaffected by cisplatin dose (P = .59). Hypertension was significantly related (P = .0066) to overall hearing threshold (4 to 12 kHz) in age- and cisplatin dose-adjusted analyses. Middle ear deficits occurred in 22.3% of patients but, as expected, were not related to cytotoxic drug dosage. Conclusion Follow-up of adult-onset cancer survivors given cisplatin should include routine inquiry for hearing status and tinnitus, referral to audiologists as clinically indicated, and hypertension control. Patients should be urged to avoid noise exposure, ototoxic drugs, and other factors that further damage hearing. (C) 2016 by American Society of Clinical Oncology C1 [Frisina, Robert D.] Univ S Florida, Tampa, FL USA. [Wheeler, Heather E.] Loyola Univ, Chicago, IL 60611 USA. [Dolan, M. Eileen] Univ Chicago, Chicago, IL 60637 USA. [Fossa, Sophie D.] Oslo Univ Hosp, Radiumhosp, Oslo, Norway. [Kerns, Sarah L.; Fung, Chunkit; Johnson, Eileen M.] Univ Rochester, Med Ctr, JP Wilmot Canc Inst, Rochester, NY 14627 USA. [Feldman, Darren R.; Budnick, Amy] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Sesso, Howard D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Beard, Clair J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Monahan, Patrick O.; Ardeshir-Rouhani-Fard, Shirin; Einhorn, Lawrence H.; Travis, Lois B.] Indiana Univ, Melvin & Bren Simon Canc Ctr, 535 Barnhill Dr,RT432, Indianapolis, IN 46204 USA. [Hamilton, Robert] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Vaughn, David J.] Univ Penn, Philadelphia, PA 19104 USA. [Lipshultz, Steven E.] Wayne State Univ, Sch Med, Childrens Hosp Michigan, Detroit, MI USA. RP Einhorn, LH (reprint author), Indiana Univ, Melvin & Bren Simon Canc Ctr, 535 Barnhill Dr,RT432, Indianapolis, IN 46204 USA. EM leinhorn@iupui.edu FU NCATS NIH HHS [UL1 TR001108]; NCI NIH HHS [K07 CA187546, R01 CA157823] NR 59 TC 3 Z9 3 U1 7 U2 7 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 AUG 10 PY 2016 VL 34 IS 23 BP 2712 EP + DI 10.1200/JCO.2016.66.8822 PG 12 WC Oncology SC Oncology GA DU8MF UT WOS:000382467000007 PM 27354478 ER PT J AU Enzinger, PC Burtness, BA Niedzwiecki, D Ye, X Douglas, K Ilson, DH Villaflor, VM Cohen, SJ Mayer, RJ Venook, A Benson, A Goldberg, RM AF Enzinger, Peter C. Burtness, Barbara Ann Niedzwiecki, Donna Ye, Xing Douglas, Kathe Ilson, David H. Villaflor, Victoria Meucci Cohen, Steven J. Mayer, Robert J. Venook, Alan Benson, Al Bowen, III Goldberg, Richard M. TI CALGB 80403 (Alliance)/E1206: A Randomized Phase II Study of Three Chemotherapy Regimens Plus Cetuximab in Metastatic Esophageal and Gastroesophageal Junction Cancers SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ADVANCED GASTRIC-CANCER; GROWTH-FACTOR RECEPTOR; ADVANCED ESOPHAGOGASTRIC CANCER; FOLINIC ACID; 1ST-LINE TREATMENT; INFUSIONAL FLUOROURACIL; WEEKLY OXALIPLATIN; COLORECTAL-CANCER; CLINICAL-TRIALS; CISPLATIN AB Purpose To determine the optimal chemotherapy backbone for testing in future US cooperative group studies for metastatic esophageal and gastroesophageal junction cancers. Cetuximab was added to each treatment arm based on promising preclinical data. Patients and Methods Patients with previously untreated metastatic esophageal or gastroesophageal junction cancer were randomly assigned at a one-to-one-to-one ratio to epirubicin, cisplatin, and continuous-infusion fluorouracil (ECF), irinotecan plus cisplatin (IC), or FOLFOX (oxaliplatin, leucovorin, and bolus and infusional fluorouracil). All treatment programs included cetuximab once per week. The primary end point was response rate. Secondary outcomes included overall survival, progression-free survival, time to treatment failure, and safety. As prespecified, primary and secondary analyses were conducted only among patients with adenocarcinoma. Results This study randomly assigned 245 patients, including 222 with adenocarcinoma. Among patients with adenocarcinoma, response rate was 60.9% (95% CI, 47.9 to 72.8) for ECF plus cetuximab, 45.0% (95% CI, 33.0 to 57.0) for IC plus cetuximab, and 54.3% (95% CI, 42.0 to 66.2) for FOLFOX plus cetuximab. Median overall survival was 11.6, 8.6, and 11.8 months; median progression-free survival was 7.1, 4.9, and 6.8 months; and median time to treatment failure was 5.6, 4.3, and 6.7 months for each of these arms, respectively. FOLFOX plus cetuximab required fewer treatment modifications compared with ECF plus cetuximab and IC plus cetuximab (P = .013), and fewer patients were removed from treatment because of an adverse event or experienced treatment-related death. Conclusion In combination with cetuximab, ECF and FOLFOX had similar efficacy, but FOLFOX was better tolerated. Although differences were nonsignificant, IC plus cetuximab seemed to be the least effective and most toxic of the three regimens tested. (C) 2016 by American Society of Clinical Oncology C1 [Enzinger, Peter C.; Mayer, Robert J.] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. [Enzinger, Peter C.; Mayer, Robert J.] Alliance Clin Trials Oncol, Boston, MA USA. [Burtness, Barbara Ann; Cohen, Steven J.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Burtness, Barbara Ann; Cohen, Steven J.; Benson, Al Bowen, III] Eastern Cooperat Oncol Grp, Amer Coll Radiol, Imaging Network Canc Res Grp, Philadelphia, PA USA. [Niedzwiecki, Donna; Ye, Xing; Douglas, Kathe] Duke Univ, Alliance Stat & Data Ctr, Durham, NC USA. [Ilson, David H.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Ilson, David H.] Alliance Clin Trials Oncol, New York, NY USA. [Villaflor, Victoria Meucci] Univ Chicago, Med & Alliance Clin Trials Oncol, Chicago, IL 60637 USA. [Benson, Al Bowen, III] Northwestern Univ, Sch Med, Chicago, IL 60611 USA. [Venook, Alan] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Venook, Alan] Alliance Clin Trials Oncol, San Francisco, CA USA. [Goldberg, Richard M.] Ohio State Univ, James Comprehens Canc Ctr, Columbus, OH 43210 USA. [Goldberg, Richard M.] Alliance Clin Trials Oncol, Columbus, OH USA. RP Enzinger, PC (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM peter_enzinger@dfci.harvard.edu FU National Cancer Institute of the National Institutes of Health (NIH) [U10CA180821, U10CA180882]; NIH [5U10CA031946-31, 5U10CA021115-38]; ImClone Systems/Bristol-Myers Squibb, Pfizer Oncology, and Sanofi FX Supported by the National Cancer Institute of the National Institutes of Health (NIH) under Awards No. U10CA180821 and U10CA180882; in part by NIH Grants No. 5U10CA031946-31 and 5U10CA021115-38; and in part by ImClone Systems/Bristol-Myers Squibb, Pfizer Oncology, and Sanofi. NR 37 TC 5 Z9 5 U1 4 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 10 PY 2016 VL 34 IS 23 BP 2736 EP + DI 10.1200/JCO.2015.65.5092 PG 11 WC Oncology SC Oncology GA DU8MF UT WOS:000382467000010 PM 27382098 ER PT J AU Wey, HY Gilbert, TM Zurcher, NR She, A Bhanot, A Taillon, BD Schroeder, FA Wang, CG Haggarty, SJ Hooker, JM AF Wey, Hsiao-Ying Gilbert, Tonya M. Zurcher, Nicole R. She, Angela Bhanot, Anisha Taillon, Brendan D. Schroeder, Fredrick A. Wang, Changing Haggarty, Stephen J. Hooker, Jacob M. TI Insights into neuroepigenetics through human histone deacetylase PET imaging SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID ALZHEIMERS-DISEASE; MOTION CORRECTION; MESSENGER-RNA; MEMORY; BRAIN; HIPPOCAMPUS; INHIBITORS; BDNF; SEGMENTATION; EXPRESSION AB Epigenetic dysfunction is implicated in many neurological and psychiatric diseases, including Alzheimer's disease and schizophrenia. Consequently, histone deacetylases (HDACs) are being aggressively pursued as therapeutic targets. However, a fundamental knowledge gap exists regarding the expression and distribution of HDACs in healthy individuals for comparison to disease states. Here, we report the first-in-human evaluation of neuroepigenetic regulation in vivo. Using positron emission tomography with [C-11] Martinostat, an imaging probe selective for class I HDACs (isoforms 1, 2, and 3), we found that HDAC expression is higher in cortical gray matter than in white matter, with conserved regional distribution patterns within and between healthy individuals. Among gray matter regions, HDAC expression was lowest in the hippocampus and amygdala. Through biochemical profiling of postmortem human brain tissue, we confirmed that [C-11] Martinostat selectively binds HDAC isoforms 1, 2, and 3, the HDAC subtypes most implicated in regulating neuroplasticity and cognitive function. In human stem cellderived neural progenitor cells, pharmacologic-level doses of Martinostat induced changes in genes closely associated with synaptic plasticity, including BDNF (brain-derived neurotrophic factor) and SYP (synaptophysin), as well as genes implicated in neurodegeneration, including GRN (progranulin), at the transcript level, in concert with increased acetylation at both histone H3 lysine 9 and histone H4 lysine 12. This study quantifies HDAC expression in the living human brain and provides the foundation for gaining unprecedented in vivo epigenetic information in health and disease. C1 [Wey, Hsiao-Ying; Gilbert, Tonya M.; Zurcher, Nicole R.; Bhanot, Anisha; Taillon, Brendan D.; Schroeder, Fredrick A.; Wang, Changing; Hooker, Jacob M.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [She, Angela; Haggarty, Stephen J.] Harvard Med Sch, Massachusetts Gen Hosp, Chem Neurobiol Lab, Dept Neurol, Boston, MA 02114 USA. [She, Angela; Haggarty, Stephen J.] Harvard Med Sch, Massachusetts Gen Hosp, Chem Neurobiol Lab, Dept Psychiat, Boston, MA 02114 USA. RP Hooker, JM (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM hooker@nmr.mgh.harvard.edu FU National Institute on Drug Abuse of the NIH [R01DA030321, K99DA037928]; Harvard/MGH Nuclear Medicine Training Program from the Department of Energy [DE-SC0008430, HHSN-271-2013-00030C]; National Institute of Biomedical Imaging and Bioengineering, NIH [P41EB015896]; Harvard Catalyst; Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH) [UL1 TR001102]; Harvard University; Bluefield Project to Cure Frontotemporal Dementia; NIH Shared Instrumentation Grant Program [S10RR017208, S10RR026666, S10RR022976, S10RR019933, S10RR023401] FX This research received funding from the National Institute on Drug Abuse of the NIH under grant numbers R01DA030321 (to J.M.H.) and K99DA037928 (to H-Y.W.). This research was also supported by the Harvard/MGH Nuclear Medicine Training Program from the Department of Energy under grants DE-SC0008430 (to H-Y.W., T.M.G., and C.W.) and HHSN-271-2013-00030C (to the Harvard Brain Tissue Resource Center). This research was carried out at the Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41EB015896, a P41 Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bioengineering, NIH. This work was conducted with support from Harvard Catalyst and the Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH Award UL1 TR001102) and financial contributions from Harvard University and its affiliated academic healthcare centers. Additional support was provided by the Bluefield Project to Cure Frontotemporal Dementia. This work also involved the use of instrumentation supported by the NIH Shared Instrumentation Grant Program, specifically grants S10RR017208, S10RR026666, S10RR022976, S10RR019933, and S10RR023401. NR 40 TC 5 Z9 5 U1 16 U2 16 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD AUG 10 PY 2016 VL 8 IS 351 AR 351ra106 DI 10.1126/scitranslmed.aaf7551 PG 10 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA DT3MB UT WOS:000381384200003 ER PT J AU Abed, J Emgard, JEM Zamir, G Faroja, M Almogy, G Grenov, A Sol, A Naor, R Pikarsky, E Atlan, KA Mellul, A Chaushu, S Manson, AL Earl, AM Ou, N Brennan, CA Garrett, WS Bachrach, G AF Abed, Jawad Emgard, Johanna E. M. Zamir, Gideon Faroja, Mouhammad Almogy, Gideon Grenov, Amalie Sol, Asaf Naor, Ronit Pikarsky, Eli Atlan, Karine A. Mellul, Anna Chaushu, Stella Manson, Abigail L. Earl, Ashlee M. Ou, Nora Brennan, Caitlin A. Garrett, Wendy S. Bachrach, Gilad TI Fap2 Mediates Fusobacterium nucleatum Colorectal Adenocarcinoma Enrichment by Binding to Tumor-Expressed Gal-GalNAc SO CELL HOST & MICROBE LA English DT Article ID PORPHYROMONAS-GINGIVALIS; MOLECULAR-FEATURES; HUMAN-LYMPHOCYTES; CELL-ADHESION; E-CADHERIN; CANCER; MICROBIOTA; CARCINOMA; DISEASE; CARCINOGENESIS AB Fusobacterium nucleatum is associated with colorectal cancer and promotes colonic tumor formation in preclinical models. However, fusobacteria are core members of the human oral microbiome and less prevalent in the healthy gut, raising questions about how fusobacteria localize to CRC. We identify a host polysaccharide and fusobacterial lectin that explicates fusobacteria abundance in CRC. Gal-GalNAc, which is overexpressed in CRC, is recognized by fusobacterial Fap2, which functions as a Gal-GalNAc lectin. F. nucleatum binding to clinical adenocarcinomas correlates with Gal-GalNAc expression and is reduced upon O-glycanase treatment. Clinical fusobacteria strains naturally lacking Fap2 or inactivated Fap2 mutants show reduced binding to Gal-GalNAc-expressing CRC cells and established CRCs in mice. Additionally, intravenously injected F. nucleatum localizes to mouse tumor tissues in a Fap2-dependent manner, suggesting that fusobacteria use a hematogenous route to reach colon adenocarcinomas. Thus, targeting F. nucleatum Fap2 or host epithelial Gal-GalNAc may reduce fusobacteria potentiation of CRC. C1 [Abed, Jawad; Emgard, Johanna E. M.; Grenov, Amalie; Sol, Asaf; Naor, Ronit; Bachrach, Gilad] Hebrew Univ Jerusalem, Hadassah Sch Dent Med, Inst Dent Sci, IL-91120 Jerusalem, Israel. [Zamir, Gideon; Faroja, Mouhammad; Almogy, Gideon] Hadassah Hebrew Univ, Med Ctr, Dept Gen Surg, IL-91120 Jerusalem, Israel. [Pikarsky, Eli] Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Immunol & Canc Res, Inst Med Res Israel Canada, IL-91120 Jerusalem, Israel. [Pikarsky, Eli; Atlan, Karine A.; Mellul, Anna] Hadassah Hebrew Univ, Med Ctr, Dept Pathol, IL-91120 Jerusalem, Israel. [Chaushu, Stella] Hebrew Univ Jerusalem, Hadassah Sch Dent Med, Dept Orthodont, IL-91120 Jerusalem, Israel. [Manson, Abigail L.; Earl, Ashlee M.; Garrett, Wendy S.] Broad Inst MIT & Harvard Univ, Cambridge, MA 02141 USA. [Ou, Nora; Brennan, Caitlin A.; Garrett, Wendy S.] Harvard TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Ou, Nora; Brennan, Caitlin A.; Garrett, Wendy S.] Harvard TH Chan Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. [Garrett, Wendy S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Bachrach, G (reprint author), Hebrew Univ Jerusalem, Hadassah Sch Dent Med, Inst Dent Sci, IL-91120 Jerusalem, Israel.; Garrett, WS (reprint author), Broad Inst MIT & Harvard Univ, Cambridge, MA 02141 USA.; Garrett, WS (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.; Garrett, WS (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA.; Garrett, WS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM wgarrett@hsph.harvard.edu; giladba@ekmd.huji.ac.il FU Israel Cancer Research Fund Project grant; Israel Science Foundation [201/15]; Hoffman-LaRoche; [RO1 CA154426] FX We thank Professor Lawrence A. Tabak for useful discussions, Professor Norman Grover for valuable assistance in statistics, and Carey Ann Gallini for proofreading. This work was supported by the Israel Cancer Research Fund Project grant and Israel Science Foundation grant 201/15 to G.B. and grant RO1 CA154426 and a Hoffman-LaRoche research grant to W.S.G. W.S.G. is a SAB member of Evelo Therapeutics and Synlogic, has received research funds from Hoffman-LaRoche, and consults for Janssen Pharmaceuticals. NR 49 TC 4 Z9 4 U1 6 U2 7 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 AUG 10 PY 2016 VL 20 IS 2 BP 215 EP 225 DI 10.1016/j.chom.2016.07.006 PG 11 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA DT6II UT WOS:000381587500013 PM 27512904 ER PT J AU Kumar, MNK Zhou, C Wu, MX AF Kumar, Mudnakudu Nagaraju Kiran Zhou, Chang Wu, Mei X. TI Laser-facilitated epicutaneous immunotherapy to IgE-mediated allergy SO JOURNAL OF CONTROLLED RELEASE LA English DT Article DE Allergic asthma; Adjuvant; Epicutaneous immunotherapy (EPIT); Immunoglobulin E (IgE); Laser and micro-fractional epicutaneous (mu EP) delivery ID CELLS; ASTHMA; VACCINATION; SAFETY; MODEL AB Allergen specific immunotherapy has been shown to be the only effective treatment for long-lasting clinical benefit to IgE-mediated allergic diseases, but a fewer than 5% of patients choose the treatment because of inconvenience and a high risk of anaphylaxis. Recently, epicutaneous allergen-specific immunotherapy (EPIT) has proven effective, yet with limitations owing to strong skin reactions. We demonstrate here safer and faster EPIT, named mu EPIT, by delivering powdered allergen and adjuvants into many micropores in the epidermis. We fabricated a microarray patch fractionally coated with a powder mixture of ovalbumin (OVA) model allergen, CpG, and 1,25-dihydroxyvitamin D-3 (VD3). Topical application of the patch onto laser-microperforated skin resulted in a high level of epidermal delivery while greatly minimizing allergen leakage into circulation system as compared to current subcutaneous immunotherapy (SCIT). Moreover, only three times of mu EPIT over two weeks could sufficiently inhibit allergen-specific IgE responses in mice suffering OVA-induced airway hyperresponsivness (AHR), which was unattainable by eight times of SCIT over three weeks. Mechanistically, mu EPIT preferably enhanced IgG2a production suggesting T(H)1-biased immune responses and induced a high level of T-regulatory (Treg) cells against repeated allergen sensitization. The immune tolerance was confirmed by marked reduction in airway wall thickness as well as eosinophil and neutrophil infiltration into the respiratory airway. The mu EPIT represents a novel and painless technology to treat IgE-mediated allergic diseases with little local skin reaction and a minimal risk of anaphylaxis. (C) 2016 Elsevier B.V. All rights reserved. C1 [Kumar, Mudnakudu Nagaraju Kiran; Zhou, Chang; Wu, Mei X.] Harvard Med Sch, Dept Dermatol, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA. RP Wu, MX (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Edwards 222,50 Blossom St, Boston, MA 02114 USA. EM mwu5@mgh.harvard.edu FU National Institute of Health [AI113458-01, AI089779] FX We thank the Pantec Biosolutions AG, Liechtenstein for the gift of P.L.E.A.S.E. Laser device and the Photopathology Core, Wellman center for their excellent technical support in obtaining tissue sections and flow cytometry analyses. This work is supported by the National Institute of Health grants AI113458-01 and AI089779 and department fund to M.X.W. NR 30 TC 0 Z9 0 U1 12 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 EI 1873-4995 J9 J CONTROL RELEASE JI J. Control. Release PD AUG 10 PY 2016 VL 235 BP 82 EP 90 DI 10.1016/j.jconrel.2016.05.057 PG 9 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA DR1ZF UT WOS:000379702700008 PM 27235977 ER PT J AU Melchardt, T Hufnagl, C Weinstock, DM Kopp, N Neureiter, D Trankenschuh, W Hackl, H Weiss, L Rinnerthaler, G Hartmann, TN Greil, R Weigert, O Egle, A AF Melchardt, Thomas Hufnagl, Clemens Weinstock, David M. Kopp, Nadja Neureiter, Daniel Traenkenschuh, Wolfgang Hackl, Hubert Weiss, Lukas Rinnerthaler, Gabriel Hartmann, Tanja N. Greil, Richard Weigert, Oliver Egle, Alexander TI Clonal evolution in relapsed and refractory diffuse large B-cell lymphoma is characterized by high dynamics of subclones SO ONCOTARGET LA English DT Article DE DLBCL; clonal evolution; TP53; tumor heterogeneity; subclonal selection ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CANCER GENES; MUTATIONS; PATTERNS; GENOME; EXPRESSION; LANDSCAPE; PROGNOSIS; DISCOVERY; IMPACT AB Little information is available about the role of certain mutations for clonal evolution and the clinical outcome during relapse in diffuse large B-cell lymphoma (DLBCL). Therefore, we analyzed formalin-fixed-paraffin-embedded tumor samples from first diagnosis, relapsed or refractory disease from 28 patients using next-generation sequencing of the exons of 104 coding genes. Non-synonymous mutations were present in 74 of the 104 genes tested. Primary tumor samples showed a median of 8 non-synonymous mutations (range: 0-24) with the used gene set. Lower numbers of non-synonymous mutations in the primary tumor were associated with a better median OS compared with higher numbers (28 versus 15 months, p=0.031). We observed three patterns of clonal evolution during relapse of disease: large global change, subclonal selection and no or minimal change possibly suggesting preprogrammed resistance. We conclude that targeted re-sequencing is a feasible and informative approach to characterize the molecular pattern of relapse and it creates novel insights into the role of dynamics of individual genes. C1 [Melchardt, Thomas; Hufnagl, Clemens; Weiss, Lukas; Rinnerthaler, Gabriel; Hartmann, Tanja N.; Greil, Richard; Egle, Alexander] Paracelsus Med Univ Salzburg, Med Dept 3, Salzburg, Austria. [Melchardt, Thomas; Hufnagl, Clemens; Weiss, Lukas; Rinnerthaler, Gabriel; Hartmann, Tanja N.; Greil, Richard; Egle, Alexander] Salzburg Canc Res Inst SCRI, Salzburg, Austria. [Melchardt, Thomas; Hufnagl, Clemens; Weiss, Lukas; Rinnerthaler, Gabriel; Hartmann, Tanja N.; Greil, Richard; Egle, Alexander] Cancer Cluster Salzburg CCS, Salzburg, Austria. [Weinstock, David M.; Kopp, Nadja] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Neureiter, Daniel; Traenkenschuh, Wolfgang] Paracelsus Med Univ Salzburg, Inst Pathol, Salzburg, Austria. [Hackl, Hubert] Med Univ Innsbruck, Bioctr, Div Bioinformat, Innsbruck, Austria. [Weigert, Oliver] Univ Munich, Univ Hosp, Med Dept 3, Lab Expt Leukemia & Lymphoma Res ELLF, Munich, Germany. [Weigert, Oliver] German Canc Consortium DKTK, Heidelberg, Germany. [Weigert, Oliver] German Canc Res Ctr, Heidelberg, Germany. RP Egle, A (reprint author), Paracelsus Med Univ Salzburg, Med Dept 3, Salzburg, Austria.; Egle, A (reprint author), Salzburg Canc Res Inst SCRI, Salzburg, Austria.; Egle, A (reprint author), Cancer Cluster Salzburg CCS, Salzburg, Austria. EM a.egle@salk.at RI Hartmann, Tanja Nicole/C-9345-2017; Greil, Richard/C-7673-2017; OI Hartmann, Tanja Nicole/0000-0002-2633-7301; Greil, Richard/0000-0002-4462-3694; Egle, Alexander/0000-0003-0648-4416; Hackl, Hubert/0000-0003-4055-3841 FU Paracelsus Medical University (PMU Grant) [E-13/17/089-MEG, R-15/03/069-MEL, E-13/18/091-EGF] FX The authors thank Paul van Hummelen and his team for assistance with sequencing. This work was supported by the Paracelsus Medical University (PMU Grant: E-13/17/089-MEG, R-15/03/069-MEL and E-13/18/091-EGF). NR 29 TC 0 Z9 0 U1 0 U2 0 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD AUG 9 PY 2016 VL 7 IS 32 BP 51494 EP 51502 DI 10.18632/oncotarget.9860 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DY9CC UT WOS:000385429100058 PM 27285986 ER PT J AU Laidlaw, KME Berhan, S Liu, SH Silvestri, G Holyoake, TL Frank, DA Aggarwal, B Bonner, MY Perrotti, D Jorgensen, HG Arbiser, JL AF Laidlaw, Kamilla M. E. Berhan, Samuel Liu, Suhu Silvestri, Giovannino Holyoake, Tessa L. Frank, David A. Aggarwal, Bharat Bonner, Michael Y. Perrotti, Danilo Jorgensen, Heather G. Arbiser, Jack L. TI Cooperation of imipramine blue and tyrosine kinase blockade demonstrates activity against chronic myeloid leukemia SO ONCOTARGET LA English DT Article DE chronic myeloid leukemia; tyrosine kinase inhibitor; imipramine blue; nilotinib; NADPH oxidase ID CHRONIC MYELOGENOUS LEUKEMIA; HEMATOPOIETIC STEM-CELLS; PROTEIN PHOSPHATASE 2A; IN-VITRO; PHILADELPHIA-CHROMOSOME; LYMPHOCYTIC-LEUKEMIA; GENOMIC INSTABILITY; IMATINIB; METASTASIS; CML AB The use of tyrosine kinase inhibitors (TKI), including nilotinib, has revolutionized the treatment of chronic myeloid leukemia (CML). However current unmet clinical needs include combating activation of additional survival signaling pathways in persistent leukemia stem cells after long-term TKI therapy. A ubiquitous signaling alteration in cancer, including CML, is activation of reactive oxygen species (ROS) signaling, which may potentiate stem cell activity and mediate resistance to both conventional chemotherapy and targeted inhibitors. We have developed a novel nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, imipramine blue (IB) that targets ROS generation. ROS levels are known to be elevated in CML with respect to normal hematopoietic stem/progenitor cells and not corrected by TKI. We demonstrate that IB has additive benefit with nilotinib in inhibiting proliferation, viability, and clonogenic function of TKI-insensitive quiescent CD34(+) CML chronic phase (CP) cells while normal CD34(+) cells retained their clonogenic capacity in response to this combination therapy in vitro. Mechanistically, the pro-apoptotic activity of IB likely resides in part through its dual ability to block NF-kappa B and re-activate the tumor suppressor protein phosphatase 2A (PP2A). Combining BCR-ABL1 kinase inhibition with NADPH oxidase blockade may be beneficial in eradication of CML and worthy of further investigation. C1 [Laidlaw, Kamilla M. E.; Berhan, Samuel; Holyoake, Tessa L.; Jorgensen, Heather G.] Univ Glasgow, Gartnavel Gen Hosp, Coll Med Vet & Life Sci, Paul OGorman Leukemia Res Ctr,Inst Canc Sci, Glasgow G12 0ZD, Lanark, Scotland. [Liu, Suhu; Frank, David A.] Harvard Med Sch, Dept Med Oncol, Dana Farber Canc Inst, Mayer 522B, Boston, MA 02215 USA. [Aggarwal, Bharat] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. [Bonner, Michael Y.; Arbiser, Jack L.] Emory Univ, Sch Med, Dept Dermatol, Atlanta, GA 30322 USA. [Bonner, Michael Y.; Arbiser, Jack L.] Atlanta Vet Adm Hosp, Atlanta, GA 30322 USA. [Silvestri, Giovannino; Perrotti, Danilo] Univ Maryland, Sch Med, Dept Med, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. RP Jorgensen, HG (reprint author), Univ Glasgow, Gartnavel Gen Hosp, Coll Med Vet & Life Sci, Paul OGorman Leukemia Res Ctr,Inst Canc Sci, Glasgow G12 0ZD, Lanark, Scotland.; Arbiser, JL (reprint author), Emory Univ, Sch Med, Dept Dermatol, Atlanta, GA 30322 USA.; Arbiser, JL (reprint author), Atlanta Vet Adm Hosp, Atlanta, GA 30322 USA. EM heather.jorgensen@glasgow.ac.uk; jarbise@emory.edu FU NIH-NCI [CA163800]; National Institutes of Health; Veterans Administration Hospital Merit Award; Margolis Foundation; Rabinowitch-Davis Foundation for Melanoma Research; Betty Minsk Foundation for Melanoma Research; Friends of Paul O'Gorman in Glasgow; Glasgow Experimental Cancer Medicine Centre (ECMC) - Cancer Research UK; Chief Scientist's Office, Scotland; Kay Kendall Leukaemia Fund [KKL501]; Howat Foundation; [RO1 AR47901]; [P30 AR42687] FX J.L.A. was supported by the grant RO1 AR47901and P30 AR42687, and NIH-NCI grant CA163800 (D.P.). Emory Skin Disease Research Core Center Grant from the National Institutes of Health, a Veterans Administration Hospital Merit Award, as well as funds from the Margolis Foundation, Rabinowitch-Davis Foundation for Melanoma Research and the Betty Minsk Foundation for Melanoma Research. H.G.J. was supported by Friends of Paul O'Gorman in Glasgow; the study was further supported by Glasgow Experimental Cancer Medicine Centre (ECMC) funded by Cancer Research UK and by the Chief Scientist's Office, Scotland; cell sorting facilities were funded by the Kay Kendall Leukaemia Fund (KKL501) and the Howat Foundation. NR 48 TC 0 Z9 0 U1 2 U2 2 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD AUG 9 PY 2016 VL 7 IS 32 BP 51651 EP 51664 DI 10.18632/oncotarget.10541 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DY9CC UT WOS:000385429100071 PM 27438151 ER PT J AU Berkovic, SF Staropoli, JF Carpenter, S Oliver, KL Kmoch, S Anderson, GW Damiano, JA Hildebrand, MS Sims, KB Cotman, SL Bahlo, M Smith, KR Cadieux-Dion, M Cossette, P Jedlickova, I Pristoupilova, A Mole, SE AF Berkovic, Samuel F. Staropoli, John F. Carpenter, Stirling Oliver, Karen L. Kmoch, Stanislav Anderson, Glenn W. Damiano, John A. Hildebrand, Michael S. Sims, Katherine B. Cotman, Susan L. Bahlo, Melanie Smith, Katherine R. Cadieux-Dion, Maxime Cossette, Patrick Jedlickova, Ivana Pristoupilova, Anna Mole, Sara E. CA ANCL Gene Discovery Consortium TI Diagnosis and misdiagnosis of adult neuronal ceroid lipofuscinosis (Kufs disease) SO NEUROLOGY LA English DT Article ID DOMINANT INHERITANCE; MUTATIONS; CLN6; NCL; DEFICIENCY; PHENOTYPES; EPILEPSY; JUVENILE; SPECTRUM; DNAJC5 AB Objective: To critically re-evaluate cases diagnosed as adult neuronal ceroid lipofuscinosis (ANCL) in order to aid clinicopathologic diagnosis as a route to further gene discovery. Methods: Through establishment of an international consortium we pooled 47 unsolved cases regarded by referring centers as ANCL. Clinical and neuropathologic experts within the Consortium established diagnostic criteria for ANCL based on the literature to assess each case. A panel of 3 neuropathologists independently reviewed source pathologic data. Cases were given a final clinicopathologic classification of definite ANCL, probable ANCL, possible ANCL, or not ANCL. Results: Of the 47 cases, only 16 fulfilled the Consortium's criteria of ANCL (5 definite, 2 probable, 9 possible). Definitive alternate diagnoses were made in 10, including Huntington disease, early-onset Alzheimer disease, Niemann-Pick disease, neuroserpinopathy, prion disease, and neurodegeneration with brain iron accumulation. Six cases had features suggesting an alternate diagnosis, but no specific condition was identified; in 15, the data were inadequate for classification. Misinterpretation of normal lipofuscin as abnormal storage material was the commonest cause of misdiagnosis. Conclusions: Diagnosis of ANCL remains challenging; expert pathologic analysis and recent molecular genetic advances revealed misdiagnoses in >1/3 of cases. We now have a refined group of cases that will facilitate identification of new causative genes. C1 [Berkovic, Samuel F.; Oliver, Karen L.; Damiano, John A.; Hildebrand, Michael S.] Univ Melbourne, Austin Hlth, Dept Med, Epilepsy Res Ctr, Heidelberg, Vic, Australia. [Staropoli, John F.] Biogen Inc, 14 Cambridge Ctr, Cambridge, MA 02142 USA. [Carpenter, Stirling] Ctr Hosp Sao Joao, Dept Pathol, Oporto, Portugal. [Kmoch, Stanislav; Jedlickova, Ivana; Pristoupilova, Anna] Charles Univ Prague, Fac Med 1, Inst Inherited Metab Disorders, Prague, Czech Republic. [Kmoch, Stanislav] Gen Univ Hosp, Prague, Czech Republic. [Anderson, Glenn W.] Great Ormond St Hosp Children NHS Fdn Trust, London, England. [Sims, Katherine B.; Cotman, Susan L.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA USA. [Sims, Katherine B.; Cotman, Susan L.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. [Bahlo, Melanie; Smith, Katherine R.] Walter & Eliza Hall Inst Med Res, Populat Hlth & Immun Div, Parkville, Vic, Australia. [Bahlo, Melanie] Univ Melbourne, Dept Math & Stat, Melbourne, Vic 3010, Australia. [Bahlo, Melanie] Univ Melbourne, Dept Med Biol, Melbourne, Vic 3010, Australia. [Cadieux-Dion, Maxime; Cossette, Patrick] Univ Montreal, Ctr Hosp Univ Montreal, Ctr Rech, Montreal, PQ H3C 3J7, Canada. [Mole, Sara E.] UCL, MRC Lab Cell Biol, Dept Genet Evolut & Environm, London WC1E 6BT, England. UCL, UCL Inst Child Hlth, London WC1E 6BT, England. RP Berkovic, SF (reprint author), Univ Melbourne, Austin Hlth, Dept Med, Epilepsy Res Ctr, Heidelberg, Vic, Australia. EM s.berkovic@unimelb.edu.au RI Pristoupilova, Anna/F-4990-2017; OI Pristoupilova, Anna/0000-0003-0047-9405; Mole, Sara/0000-0003-4385-4957 FU National Health and Medical Research Council Program [628952]; Charles University institutional programs [PRVOUK-P24/LF1/3, UNCE 204011, SVV2016/260148]; NPU II from the Ministry of Education of the Czech Republic [LQ1604]; Ministry of Health of the Czech Republic [15-28208A]; GA UK [269615, 1402213]; Genomic facility in Motol University Hospital in Prague [OPPK.CZ.2.16/3.100/24022]; Rare NCL Gene Consortium; USA Batten Disease Support and Research Association; National Institutes of Health: National Institute of Neurologic Disorders Stroke [R01NS073813]; Fonds de Recherche du Quebec-Sante (FRQS) FX S.F.B. was supported by a National Health and Medical Research Council Program Grant (ID: 628952). S.K., I.J., and A.P. are funded by Charles University institutional programs PRVOUK-P24/LF1/3, UNCE 204011, and SVV2016/260148 and by the project LQ1604 NPU II from the Ministry of Education of the Czech Republic. This work was specifically supported by grant 15-28208A from the Ministry of Health of the Czech Republic and GA UK No. 269615 (I.J.) and No. 1402213 (A.P.). Instrumental support for exome and gene panel sequencing was provided by the Genomic facility in Motol University Hospital in Prague (OPPK.CZ.2.16/3.100/24022). S.E.M. received specific funding towards the work of the Rare NCL Gene Consortium and Kufs disease from the USA Batten Disease Support and Research Association. S.L.C. is funded by the National Institutes of Health: National Institute of Neurologic Disorders & Stroke (R01NS073813). M.C.-D. is supported by the Fonds de Recherche du Quebec-Sante (FRQS). NR 37 TC 0 Z9 0 U1 4 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD AUG 9 PY 2016 VL 87 IS 6 BP 579 EP 584 DI 10.1212/WNL.0000000000002943 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA DU6LT UT WOS:000382327000011 PM 27412140 ER PT J AU Shefner, JM Liu, DW Leitner, ML Schoenfeld, D Johns, DR Ferguson, T Cudkowicz, M AF Shefner, Jeremy M. Liu, Dawei Leitner, Melanie L. Schoenfeld, David Johns, Donald R. Ferguson, Toby Cudkowicz, Merit TI Quantitative strength testing in ALS clinical trials SO NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; PLACEBO-CONTROLLED TRIAL; DISEASE PROGRESSION; DOUBLE-BLIND; EFFICACY; SAFETY AB Objective: To study the attributes of quantitative strength testing using hand-held dynamometry (HHD) as an efficacy measure in 2 large phase 3 amyotrophic lateral sclerosis (ALS) trials. Methods: In the phase 3 trials of ceftriaxone and dexpramipexole, 513 and 943 patients, respectively, were enrolled in double-blind, randomized, placebo-controlled trials with planned follow-up of at least 1 year. Patients were studied every 3 months in the ceftriaxone study and every 2 months in the dexpramipexole study. Evaluators of HHD were trained and had to show evidence of adequate performance of strength testing; the testing paradigm involved testing 9 muscle groups in the upper and lower extremity bilaterally. Neither drug significantly affected any outcome measure. Strength measurements were evaluated by individual muscle and by megascores, which averaged scaled strength measures to produce an overall measure of muscle strength. Results: A measure combining rate of decline with both within-and between-patient variabilities of measurement, the coefficient of variation for rate of change, was calculated, and showed that HHD overall performed slightly less well than Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R) but better than vital capacity. Individual muscles were highly correlated to the identical muscles on the contralateral side, as well as to other muscles in the same body region. Strength decline was correlated both with ALSFRS-R and vital capacity. Conclusion: Quantitative strength testing using HHD is a reliable and reproducible measure of decline in ALS. C1 [Shefner, Jeremy M.] Barrow Neurol Inst, Dept Neurol, Phoenix, AZ 85013 USA. [Liu, Dawei; Leitner, Melanie L.; Johns, Donald R.; Ferguson, Toby] Biogen, Cambridge, MA USA. [Schoenfeld, David; Cudkowicz, Merit] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Shefner, JM (reprint author), Barrow Neurol Inst, Dept Neurol, Phoenix, AZ 85013 USA. EM Jeremy.Shefner@DignityHealth.org FU NIH/National Institute of Neurological Disorders and Stroke [U01NS077179]; Biogen-Idec FX The dexpramipexole clinical trial was funded entirely by Biogen-Idec. The ceftriaxone clinical trial was funded by NIH/National Institute of Neurological Disorders and Stroke (U01NS077179, PI Dr. Merit Cudkowicz). NR 16 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD AUG 9 PY 2016 VL 87 IS 6 BP 617 EP 624 DI 10.1212/WNL.0000000000002941 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA DU6LT UT WOS:000382327000016 PM 27385750 ER PT J AU Chen, KJ Shanmugam, NKN Pazos, MA Hurley, BP Cherayil, BJ AF Chen, Kejie Shanmugam, Nanda Kumar N. Pazos, Michael A. Hurley, Bryan P. Cherayil, Bobby J. TI Commensal Bacteria-Induced Inflammasome Activation in Mouse and Human Macrophages Is Dependent on Potassium Efflux but Does Not Require Phagocytosis or Bacterial Viability SO PLOS ONE LA English DT Article ID NLRP3 INFLAMMASOME; INTESTINAL INFLAMMATION; IL-1-BETA PRODUCTION; CROHNS-DISEASE; RECEPTOR; AUTOPHAGY; PROTEIN; INFECTION; DECTIN-1; CELLS AB Gut commensal bacteria contribute to the pathogenesis of inflammatory bowel disease, in part by activating the inflammasome and inducing secretion of interleukin-1 beta (IL-1 beta). Although much has been learned about inflammasome activation by bacterial pathogens, little is known about how commensals carry out this process. Accordingly, we investigated the mechanism of inflammasome activation by representative commensal bacteria, the Gram-positive Bifidobacterium longum subspecies infantis and the Gram-negative Bacteroides fragilis. B. infantis and B. fragilis induced IL-1 beta secretion by primary mouse bone marrow-derived macrophages after overnight incubation. IL-1 beta secretion also occurred in response to heat-killed bacteria and was only partly reduced when phagocytosis was inhibited with cytochalasin D. Similar results were obtained with a wild-type immortalized mouse macrophage cell line but neither B. infantis nor B. fragilis induced IL-1 beta secretion in a mouse macrophage line lacking the nucleotide-binding/leucine-rich repeat pyrin domain containing 3 (NLRP3) inflammasome. IL-1 beta secretion in response to B. infantis and B. fragilis was significantly reduced when the wild-type macrophage line was treated with inhibitors of potassium efflux, either increased extracellular potassium concentrations or the channel blocker ruthenium red. Both live and heat-killed B. infantis and B. fragilis also induced IL-1 beta secretion by human macrophages (differentiated THP-1 cells or primary monocyte-derived macrophages) after 4 hours of infection, and the secretion was inhibited by raised extracellular potassium and ruthenium red but not by cytochalasin D. Taken together, our findings indicate that the commensal bacteria B. infantis and B. fragilis activate the NLRP3 inflammasome in both mouse and human macrophages by a mechanism that involves potassium efflux and that does not require bacterial viability or phagocytosis. C1 [Chen, Kejie; Shanmugam, Nanda Kumar N.; Pazos, Michael A.; Hurley, Bryan P.; Cherayil, Bobby J.] Massachusetts Gen Hosp, Dept Pediat, Mucosal Immunol & Biol Res Ctr, Boston, MA 02114 USA. [Chen, Kejie; Shanmugam, Nanda Kumar N.; Pazos, Michael A.; Hurley, Bryan P.; Cherayil, Bobby J.] Harvard Med Sch, Boston, MA 02115 USA. [Chen, Kejie] Sichuan Agr Univ, Coll Vet Med, Yaan, Sichuan, Peoples R China. RP Cherayil, BJ (reprint author), Massachusetts Gen Hosp, Dept Pediat, Mucosal Immunol & Biol Res Ctr, Boston, MA 02114 USA.; Cherayil, BJ (reprint author), Harvard Med Sch, Boston, MA 02115 USA. EM cherayil@helix.mgh.harvard.edu FU National Institute of Allergy and Infectious Diseases [R01AI089700, R01AI095338]; China Scholarship Council; Cystic Fibrosis Foundation [PAZOS13F0] FX This work was supported by grant numbers R01AI089700 and R01AI095338 from the National Institute of Allergy and Infectious Diseases to BJC and BPH, respectively. KC was supported by funding from the China Scholarship Council and MAP by fellowship number PAZOS13F0 from the Cystic Fibrosis Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 0 Z9 0 U1 8 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 AUG 9 PY 2016 VL 11 IS 8 AR e0160937 DI 10.1371/journal.pone.0160937 PG 20 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DT3IK UT WOS:000381374200082 PM 27505062 ER PT J AU O'Donnell, PE Ye, XZ DeChellis, MA Davis, VM Duan, SZ Mortensen, RM Milstone, DS AF O'Donnell, Peter E. Ye, Xiu Zhen DeChellis, Melissa A. Davis, Vannessa M. Duan, Sheng Zhong Mortensen, Richard M. Milstone, David S. TI Lipodystrophy, Diabetes and Normal Serum Insulin in PPAR gamma-Deficient Neonatal Mice SO PLOS ONE LA English DT Article ID ACTIVATED-RECEPTOR-GAMMA; ADIPOSE-TISSUE; ADIPOCYTE DIFFERENTIATION; BETA-CELLS; RESISTANCE; FAT; DISRUPTION; EXPRESSION; KNOCKOUT; MUSCLE AB Peroxisome proliferator activated receptor gamma (PPAR gamma) is a pleiotropic ligand activated transcription factor that acts in several tissues to regulate adipocyte differentiation, lipid metabolism, insulin sensitivity and glucose homeostasis. PPAR gamma also regulates cardiomyocyte homeostasis and by virtue of its obligate role in placental development is required for embryonic survival. To determine the postnatal functions of PPAR gamma in vivo we studied globally deficient neonatal mice produced by epiblast-restricted elimination of PPAR gamma. PPAR gamma-rescued placentas support development of PPAR gamma-deficient embryos that are viable and born in near normal numbers. However, PPAR gamma-deficient neonatal mice show severe lipodystrophy, lipemia, hepatic steatosis with focal hepatitis, relative insulin deficiency and diabetes beginning soon after birth and culminating in failure to thrive and neonatal lethality between 4 and 10 days of age. These abnormalities are not observed with selective PPAR gamma 2 deficiency or with deficiency restricted to hepatocytes, skeletal muscle, adipocytes, cardiomyocytes, endothelium or pancreatic beta cells. These observations suggest important but previously unappreciated functions for PPAR gamma 1 in the neonatal period either alone or in combination with PPAR gamma 2 in lipid metabolism, glucose homeostasis and insulin sensitivity. C1 [O'Donnell, Peter E.; Ye, Xiu Zhen; DeChellis, Melissa A.; Davis, Vannessa M.; Milstone, David S.] Brigham & Womens Hosp, Dept Pathol, Div Vasc Res, Boston, MA 02115 USA. [O'Donnell, Peter E.; Ye, Xiu Zhen; DeChellis, Melissa A.; Davis, Vannessa M.; Milstone, David S.] Harvard Med Sch, Boston, MA 02115 USA. [Duan, Sheng Zhong; Mortensen, Richard M.] Univ Michigan, Sch Med, Dept Physiol, Ann Arbor, MI USA. [O'Donnell, Peter E.] Novartis Inst Biomed Res, Cambridge, MA USA. [DeChellis, Melissa A.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Duan, Sheng Zhong] Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai, Peoples R China. RP Milstone, DS (reprint author), Brigham & Womens Hosp, Dept Pathol, Div Vasc Res, Boston, MA 02115 USA.; Milstone, DS (reprint author), Harvard Med Sch, Boston, MA 02115 USA. EM milstone@rics.bwh.harvard.edu FU National Institute of Child Health and Human Development [R01HD40895]; National Heart, Lung and Blood Institute [P01HL36028]; pilot project and cores of the Michigan Diabetes Research and Training Center from the National Institute of Diabetes & Digestive & Kidney Diseases (RMM) [NIH5P60 DK20572]; Tissue Microarray and Imaging Core Facility of the Dana-Farber/Harvard Cancer Center [P30 CA06516]; Department of Pathology, Brigham and Women's Hospital FX This work was supported by grants from the National Institute of Child Health and Human Development R01HD40895 (DSM), the National Heart, Lung and Blood Institute P01HL36028 (DSM), a pilot project and cores of the Michigan Diabetes Research and Training Center (NIH5P60 DK20572) from the National Institute of Diabetes & Digestive & Kidney Diseases (RMM), the Tissue Microarray and Imaging Core Facility of the Dana-Farber/Harvard Cancer Center (P30 CA06516) and by the Department of Pathology, Brigham and Women's Hospital (DSM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 0 Z9 0 U1 2 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 9 PY 2016 VL 11 IS 8 AR e0160636 DI 10.1371/journal.pone.0160636 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DT3IK UT WOS:000381374200049 PM 27505464 ER PT J AU Tian, B Maidana, DE Dib, B Miller, JB Bouzika, P Miller, JW Vavvas, DG Lin, HJ AF Tian, Bo Maidana, Daniel E. Dib, Bernard Miller, John B. Bouzika, Peggy Miller, Joan W. Vavvas, Demetrios G. Lin, Haijiang TI miR-17-3p Exacerbates Oxidative Damage in Human Retinal Pigment Epithelial Cells SO PLOS ONE LA English DT Article ID MITOCHONDRIAL SUPEROXIDE-DISMUTASE; MACULAR DEGENERATION; ARPE-19 CELLS; ENDOTHELIAL-CELLS; GENE-EXPRESSION; DOWN-REGULATION; MOUSE MODEL; RPE CELLS; STRESS; THIOREDOXIN AB Oxidative stress has been shown to contribute to the development of age-related macular degeneration (AMD). MicroRNAs (miRNA) are small non-coding RNA molecules that function in RNA silencing and post-transcriptional regulation of gene expression. We showed miR-17-3p to be elevated in macular RPE cells from AMD patients and in ARPE-19 cells under oxidative stress. Transfection of miR-17-3p mimic in ARPE-19 induced cell death and exacerbated oxidative lethality that was alleviated by miR-17-3p inhibitor. The expression of antioxidant enzymes manganese superoxide dismutase (MnSOD) and thioredoxin reductase-2 (TrxR(2)) were suppressed by miR-17-3p mimic and reversed by miR-17-3p inhibitor. These results suggest miR-17-3p aggravates oxidative damage-induced cell death in human RPE cells, while miR-17-3p inhibitor acts as a potential protector against oxidative stress by regulating the expression of antioxidant enzymes. C1 [Tian, Bo; Maidana, Daniel E.; Dib, Bernard; Miller, John B.; Bouzika, Peggy; Miller, Joan W.; Vavvas, Demetrios G.; Lin, Haijiang] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Retina Serv, Angiogenesis Lab,Dept Ophthalmol, Boston, MA 02115 USA. [Tian, Bo] Zhengzhou Univ, Affiliated Hosp 1, Dept Ophthalmol, Zhengzhou, Henan, Peoples R China. RP Vavvas, DG; Lin, HJ (reprint author), Harvard Med Sch, Massachusetts Eye & Ear Infirm, Retina Serv, Angiogenesis Lab,Dept Ophthalmol, Boston, MA 02115 USA. EM Demetrios_Vavvas@meei.harvard.edu; Haijiang_Lin@meei.harvard.edu FU NEI [R21EY023079-01A1, EY014104]; Yeatts Family Foundation; Loefflers Family Fund; Macula Society Research Grant award; Physician Scientist Award; research to prevent blindness foundation; Bayer Healthcare Global Ophthalmology Award FX This work was supported by: NEI R21EY023079-01A1 (DGV); the Yeatts Family Foundation (DGV, JWM); the Loefflers Family Fund (DGV, JWM); the 2013 Macula Society Research Grant award (DGV); a Physician Scientist Award (DGV), an unrestricted grant (JWM) from the research to prevent blindness foundation; NEI grant EY014104 (Meei Core Grant); and Bayer Healthcare Global Ophthalmology Award (DEM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; This work was supported by: NEI R21EY023079-01A1 (DGV); the Yeatts Family Foundation (DGV, JWM); the Loefflers Family Fund (DGV, JWM); the 2013 Macula Society Research Grant award (DGV); a Physician Scientist Award (DGV), an unrestricted grant (JWM) from the research to prevent blindness foundation; NEI grant EY014104 (Meei Core Grant); and Bayer Healthcare Global Ophthalmology Award (DEM). The authors would like to thank Kassandra Kosmidou for proofreading this manuscript. NR 75 TC 0 Z9 0 U1 2 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 9 PY 2016 VL 11 IS 8 AR e0160887 DI 10.1371/journal.pone.0160887 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DT3IK UT WOS:000381374200073 PM 27505139 ER PT J AU Chen, KY Cypess, AM Laughlin, MR Haft, CR Hu, HH Bredella, MA Enerback, S Kinahan, PE Lichtenbelt, WV Lin, FI Sunderland, JJ Virtanen, KA Wahl, RL AF Chen, Kong Y. Cypess, Aaron M. Laughlin, Maren R. Haft, Carol R. Hu, Houchun Harry Bredella, Miriam A. Enerback, Sven Kinahan, Paul E. Lichtenbelt, Wouter van Marken Lin, Frank I. Sunderland, John J. Virtanen, Kirsi A. Wahl, Richard L. TI Brown Adipose Reporting Criteria in Imaging STudies (BARCIST 1.0): Recommendations for Standardized FDG-PET/CT Experiments in Humans SO CELL METABOLISM LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; TYPE-2 DIABETES-MELLITUS; ADULT HUMANS; F-18-FDG PET/CT; ENERGY-EXPENDITURE; OXIDATIVE-METABOLISM; INSULIN SENSITIVITY; COMPUTED-TOMOGRAPHY; TISSUE ACTIVITY; COLD-EXPOSURE AB Human brown adipose tissue (BAT) presence, metabolic activity, and estimated mass are typically measured by imaging [18F]fluorodeoxyglucose (FDG) uptake in response to cold exposure in regions of the body expected to contain BAT, using positron emission tomography combined with X-ray computed tomography (FDG-PET/CT). Efforts to describe the epidemiology and biology of human BAT are hampered by diverse experimental practices, making it difficult to directly compare results among laboratories. An expert panel was assembled by the National Institute of Diabetes and Digestive and Kidney Diseases on November 4, 2014 to discuss minimal requirements for conducting FDG-PET/CT experiments of human BAT, data analysis, and publication of results. This resulted in Brown Adipose Reporting Criteria in Imaging STudies (BARCIST 1.0). Since there are no fully validated best practices at this time, panel recommendations are meant to enhance comparability across experiments, but not to constrain experimental design or the questions that can be asked. C1 [Chen, Kong Y.; Cypess, Aaron M.; Laughlin, Maren R.; Haft, Carol R.] NIDDK, NIH, Bethesda, MD 20892 USA. [Hu, Houchun Harry] Phoenix Childrens Hosp, Phoenix, AZ 85016 USA. [Bredella, Miriam A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bredella, Miriam A.] Harvard Med Sch, Boston, MA 02114 USA. [Enerback, Sven] Univ Gothenburg, S-40530 Gothenburg, Sweden. [Kinahan, Paul E.] Univ Washington, Seattle, WA 98105 USA. [Lichtenbelt, Wouter van Marken] Maastricht Univ, NL-6211 LK Maastricht, Netherlands. [Lin, Frank I.] NCI, NIH, Bethesda, MD 20892 USA. [Sunderland, John J.] Univ Iowa, Iowa City, IA 52242 USA. [Virtanen, Kirsi A.] Turku Univ Hosp, Turku 20500, Finland. [Virtanen, Kirsi A.] Univ Turku, SF-20500 Turku, Finland. [Wahl, Richard L.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. RP Chen, KY; Cypess, AM; Laughlin, MR (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA. EM kong.chen@nih.gov; aaron.cypess@nih.gov; maren.laughlin@nih.gov OI Chen, Kong/0000-0002-0306-1904 FU Intramural Research Program of the NIH; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Cancer Institute (NCI) FX This research was supported in part by the Intramural Research Program of the NIH, The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and the National Cancer Institute (NCI). NR 74 TC 4 Z9 4 U1 3 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD AUG 9 PY 2016 VL 24 IS 2 BP 210 EP 222 DI 10.1016/j.cmet.2016.07.014 PG 13 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA DT3PH UT WOS:000381392800010 PM 27508870 ER PT J AU Khetarpal, SA Schjoldager, KT Christoffersen, C Raghavan, A Edmondson, AC Reutter, HM Ahmed, B Ouazzani, R Peloso, GM Vitali, C Zhao, W Somasundara, AVH Millar, JS Park, Y Fernando, G Livanov, V Choi, S Noe, E Patel, P Ho, SP Kirchgessner, TG Wandall, HH Hansen, L Bennett, EP Vakhrushev, SY Saleheen, D Kathiresan, S Brown, CD Abou Jamra, R LeGuern, E Clausen, H Rader, DJ AF Khetarpal, Sumeet A. Schjoldager, Katrine T. Christoffersen, Christina Raghavan, Avanthi Edmondson, Andrew C. Reutter, Heiko M. Ahmed, Bouhouche Ouazzani, Reda Peloso, Gina M. Vitali, Cecilia Zhao, Wei Somasundara, Amritha Varshini Hanasoge Millar, John S. Park, YoSon Fernando, Gayani Livanov, Valentin Choi, Seungbum Noe, Eric Patel, Pritesh Ho, Siew Peng Kirchgessner, Todd G. Wandall, Hans H. Hansen, Lars Bennett, Eric P. Vakhrushev, Sergey Y. Saleheen, Danish Kathiresan, Sekar Brown, Christopher D. Abou Jamra, Rami LeGuern, Eric Clausen, Henrik Rader, Daniel J. CA Myocardial Infarction Exome TI Loss of Function of GALNT2 Lowers High-Density Lipoproteins in Humans, Nonhuman Primates, and Rodents SO CELL METABOLISM LA English DT Article ID PHOSPHOLIPID-TRANSFER PROTEIN; O-GLYCOSYLATION; CHOLESTEROL HOMEOSTASIS; PLASMA; LOCI; SECRETION; VARIANTS; MUTATION; GLYCOPROTEOME; ASSOCIATION AB Human genetics studies have implicated GALNT2, encoding GalNAc-T2, as a regulator of high-density lipoprotein cholesterol (HDL-C) metabolism, but the mechanisms relating GALNT2 to HDL-C remain unclear. We investigated the impact of homozygous GALNT2 deficiency on HDL-C in humans and mammalian models. We identified two humans homozygous for loss-of-function mutations in GALNT2 who demonstrated low HDL-C. We also found that GALNT2 loss of function in mice, rats, and nonhuman primates decreased HDL-C. O-glycoproteomics studies of a human GALNT2-deficient subject validated ANGPTL3 and ApoC-III as GalNAc-T2 targets. Additional glycoproteomics in rodents identified targets influencing HDL-C, including phospholipid transfer protein (PLTP). GALNT2 deficiency reduced plasma PLTP activity in humans and rodents, and in mice this was rescued by reconstitution of hepatic Galnt2. We also found that GALNT2 GWAS SNPs associated with reduced HDL-C also correlate with lower hepatic GALNT2 expression. These results posit GALNT2 as a direct modulator of HDL metabolism across mammals. C1 [Khetarpal, Sumeet A.; Raghavan, Avanthi; Edmondson, Andrew C.; Vitali, Cecilia; Zhao, Wei; Somasundara, Amritha Varshini Hanasoge; Millar, John S.; Park, YoSon; Brown, Christopher D.; Rader, Daniel J.] Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA. [Khetarpal, Sumeet A.; Raghavan, Avanthi; Edmondson, Andrew C.; Vitali, Cecilia; Zhao, Wei; Somasundara, Amritha Varshini Hanasoge; Millar, John S.; Rader, Daniel J.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Schjoldager, Katrine T.; Wandall, Hans H.; Hansen, Lars; Bennett, Eric P.; Vakhrushev, Sergey Y.; Clausen, Henrik] Univ Copenhagen, Inst Hlth Sci, Copenhagen Ctr Glyc, Dept Cellular & Mol Med, Blegdamsvej 3, DK-2200 Copenhagen, Denmark. [Schjoldager, Katrine T.; Wandall, Hans H.; Hansen, Lars; Bennett, Eric P.; Vakhrushev, Sergey Y.; Clausen, Henrik] Univ Copenhagen, Inst Hlth Sci, Copenhagen Ctr Glyc, Dept Odontol, Blegdamsvej 3, DK-2200 Copenhagen, Denmark. [Christoffersen, Christina] Univ Copenhagen, Rigshosp, Dept Clin Biochem, Blegdamsvej 3, DK-2200 Copenhagen, Denmark. [Christoffersen, Christina] Univ Copenhagen, Dept Biomed Sci, Blegdamsvej 3, DK-2200 Copenhagen, Denmark. [Reutter, Heiko M.] Univ Bonn, Inst Human Genet, D-53012 Bonn, Germany. [Reutter, Heiko M.] Univ Bonn, Dept Neonatol & Pediat Intens Care, D-53012 Bonn, Germany. [Ahmed, Bouhouche] Mohammed V Univ, Sch Med, Res Team Neurodegenerat Dis, Rabat 10100, Morocco. [Ahmed, Bouhouche] Mohammed V Univ, Pharm, Rabat 10100, Morocco. [Ouazzani, Reda] CHIS Ibn Sina, Hosp Special, Neurophysiol Div, Rabat 6402, Morocco. [Peloso, Gina M.; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Peloso, Gina M.; Kathiresan, Sekar; Myocardial Infarction Exome] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Peloso, Gina M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Fernando, Gayani; Kirchgessner, Todd G.] Bristol Myers Squibb, Dept Cardiovasc Drug Discovery, Pennington, NJ 08534 USA. [Livanov, Valentin; Patel, Pritesh; Ho, Siew Peng] Bristol Myers Squibb, Dept Appl Genom, Pennington, NJ 08534 USA. [Choi, Seungbum] Gachon Univ, Gacheon Cardiovasc Res Inst, Inchon 21565, South Korea. [Noe, Eric; LeGuern, Eric] Univ Paris 06, INSERM, Sorbonne Univ, UMR S 1127,U1127,CNRS,UMR 7225,ICM, F-75013 Paris, France. [Noe, Eric; LeGuern, Eric] Pitie La Salpetriere Hosp, AP HP, Dept Genet, F-75013 Paris, France. [Saleheen, Danish] Univ Cambridge, Dept Publ Hlth & Primary Care, Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England. [Saleheen, Danish] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Saleheen, Danish] Ctr Noncommunicable Dis, Karachi 75300, Pakistan. [Kathiresan, Sekar] Harvard Med Sch, Dept Med, Boston, MA 02114 USA. [Abou Jamra, Rami] Univ Leipzig, Hosp & Clin, Inst Human Genet, D-04103 Leipzig, Germany. [Abou Jamra, Rami] Univ Erlangen Nurnberg, Inst Human Genet, D-91054 Erlangen, Germany. RP Rader, DJ (reprint author), Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA.; Rader, DJ (reprint author), Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.; Schjoldager, KT (reprint author), Univ Copenhagen, Inst Hlth Sci, Copenhagen Ctr Glyc, Dept Cellular & Mol Med, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.; Schjoldager, KT (reprint author), Univ Copenhagen, Inst Hlth Sci, Copenhagen Ctr Glyc, Dept Odontol, Blegdamsvej 3, DK-2200 Copenhagen, Denmark. EM schjoldager@sund.ku.dk; rader@mail.med.upenn.edu OI Wandall, Hans H./0000-0003-0240-9232; Brown, Christopher/0000-0002-3785-5008 FU Danish Research Councils; Kirsten og Freddy Johansen Fonden; A.P. Moller og Hustru Chastine Mc-Kinney Mollers Fond til Almene Formaal; Novo Nordisk Foundation; University of Copenhagen [CDO2016]; Danish National Research Foundation [DNRF107]; NIH [R01 HL111398, R01 HL089309]; Foundation Leducq [10CVD03]; German Research Foundation (DFG) [AB393/2-2]; Mizutani Foundation FX We acknowledge Thomas F. Vogt, John S. Mudgett, and Merck Research Laboratories for providing Galnt2 KO mice. We thank the UPenn Functional Genomics Core at DRC (P30-DK19525) for RNA sequencing and the University of Pennsylvania Preclinical Vector Core supported by the NHLBI Gene Therapy Resource Program (GTRP) for providing gene vectors used in this study. This work was supported by The Danish Research Councils (Sapere Aude Research Talent Grant to K.T.S.), Kirsten og Freddy Johansen Fonden, A.P. Moller og Hustru Chastine Mc-Kinney Mollers Fond til Almene Formaal, The Novo Nordisk Foundation, a program of excellence from the University of Copenhagen (CDO2016), the Danish National Research Foundation (DNRF107), NIH grants R01 HL111398 and R01 HL089309, and grant 10CVD03 from the Foundation Leducq to D.J.R; the German Research Foundation (DFG) with funding AB393/2-2 to R.A.J.; and the Mizutani Foundation to S.Y.V. We also thank Pr. El Fahime El Mostafa for hosting K.T.S. in his laboratory. NR 35 TC 3 Z9 3 U1 3 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD AUG 9 PY 2016 VL 24 IS 2 BP 234 EP 245 DI 10.1016/j.cmet.2016.07.012 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA DT3PH UT WOS:000381392800012 PM 27508872 ER PT J AU Yu, VWC Lymperi, S Oki, T Jones, A Swiatek, P Vasic, R Ferraro, F Scadden, DT AF Yu, Vionnie W. C. Lymperi, Stefania Oki, Toshihiko Jones, Alexandra Swiatek, Peter Vasic, Radovan Ferraro, Francesca Scadden, David T. TI Distinctive Mesenchymal-Parenchymal Cell Pairings Govern B Cell Differentiation in the Bone Marrow SO STEM CELL REPORTS LA English DT Article ID HEMATOPOIETIC STEM-CELL; GROWTH-FACTOR-I; OSTEOBLAST DIFFERENTIATION; NICHE; PROGENITORS; MAINTENANCE; LINEAGE; OSTERIX; MICE; IDENTIFICATION AB Bone marrow niches for hematopoietic progenitor cells are not well defined despite their critical role in blood homeostasis. We previously found that cells expressing osteocalcin, a marker of mature osteolineage cells, regulate the production of thymic-seeding T lymphoid progenitors. Here, using a selective cell deletion strategy, we demonstrate that a subset of mesenchymal cells expressing osterix, a marker of bone precursors in the adult, serve to regulate the maturation of early B lymphoid precursors by promoting pro-B to pre-B cell transition through insulin-like growth factor 1 (IGF-1) production. Loss of Osx(+) cells or Osx-specific deletion of IGF-1 led to a failure of B cell maturation and the impaired adaptive immune response. These data highlight the notion that bone marrow is a composite of specialized niches formed by pairings of specific mesenchymal cells with parenchymal stem or lineage committed progenitor cells, thereby providing distinctive functional units to regulate hematopoiesis. C1 [Yu, Vionnie W. C.; Lymperi, Stefania; Oki, Toshihiko; Jones, Alexandra; Swiatek, Peter; Vasic, Radovan; Ferraro, Francesca; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Yu, Vionnie W. C.; Lymperi, Stefania; Oki, Toshihiko; Jones, Alexandra; Swiatek, Peter; Vasic, Radovan; Ferraro, Francesca; Scadden, David T.] Harvard Stem Cell Inst, Boston, MA 02114 USA. [Yu, Vionnie W. C.; Lymperi, Stefania; Oki, Toshihiko; Jones, Alexandra; Swiatek, Peter; Vasic, Radovan; Ferraro, Francesca; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02139 USA. [Ferraro, Francesca] Univ Penn Hlth Syst, Penn Hosp, Dept Med, 800 Spruce St, Philadelphia, PA 19107 USA. [Scadden, David T.] Massachusetts Gen Hosp, Harvard Stem Cell Inst, Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02115 USA. RP Ferraro, F; Scadden, DT (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.; Ferraro, F; Scadden, DT (reprint author), Harvard Stem Cell Inst, Boston, MA 02114 USA.; Ferraro, F; Scadden, DT (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02139 USA.; Ferraro, F (reprint author), Univ Penn Hlth Syst, Penn Hosp, Dept Med, 800 Spruce St, Philadelphia, PA 19107 USA.; Scadden, DT (reprint author), Massachusetts Gen Hosp, Harvard Stem Cell Inst, Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02115 USA. EM f.ferraro.mgh@gmail.com; david_scadden@harvard.edu FU NIH - Gerald and Darlene Jordan Chair of Medicine [HL044851, HL096372, EB014703] FX We thank Dr. Andrew P. McMahon at Harvard University for his generosity in providing the Osx1-GFP::Cre mouse strain. We are thankful to Dr. Rene Maher who provided the Rosa 26-loxP-STOP-loxP-membrane Cherry (Rosa-mCh) mouse. We thank the Harvard Stem Cell Institute Flow Cytometry Core for assistance in flow cytometry. This work was supported by NIH HL044851, HL096372, EB014703 to D.T.S. who was also supported by the Gerald and Darlene Jordan Chair of Medicine. NR 38 TC 1 Z9 1 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2213-6711 J9 STEM CELL REP JI Stem Cell Rep. PD AUG 9 PY 2016 VL 7 IS 2 BP 220 EP 235 DI 10.1016/j.stemcr.2016.06.009 PG 16 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA DT3KW UT WOS:000381380900008 PM 27453006 ER PT J AU Jourdain, G Ngo-Giang-Huong, N Cressey, TR Hua, L Harrison, L Tierney, C Salvadori, N Decker, L Traisathit, P Sirirungsi, W Khamduang, W Bowonwatanuwong, C Puthanakit, T Siberry, GK Watts, DH Murphy, TV Achalapong, J Hongsiriwon, S Klinbuayaem, V Thongsawat, S Chung, RT Pol, S Chotivanich, N AF Jourdain, Gonzague Ngo-Giang-Huong, Nicole Cressey, Tim R. Hua, Lei Harrison, Linda Tierney, Camlin Salvadori, Nicolas Decker, Luc Traisathit, Patrinee Sirirungsi, Wasna Khamduang, Woottichai Bowonwatanuwong, Chureeratana Puthanakit, Thanyawee Siberry, George K. Watts, Diane Heather Murphy, Trudy V. Achalapong, Jullapong Hongsiriwon, Suchat Klinbuayaem, Virat Thongsawat, Satawat Chung, Raymond T. Pol, Stanislas Chotivanich, Nantasak TI Prevention of mother-to-child transmission of hepatitis B virus: a phase III, placebo-controlled, double-blind, randomized clinical trial to assess the efficacy and safety of a short course of tenofovir disoproxil fumarate in women with hepatitis B virus e-antigen SO BMC INFECTIOUS DISEASES LA English DT Article ID PERINATAL TRANSMISSION; INFANT TRANSMISSION; SURFACE-ANTIGEN; INFECTION; PREGNANCY; METAANALYSIS AB Background: Chronic hepatitis B virus (HBV) infection is complicated by cirrhosis and liver cancer. In Thailand, 6-7 % of adults are chronically infected with HBV. The risk of mother-to-child transmission (MTCT) of HBV has been estimated to be about 12 % when mothers have a high hepatitis B viral load, even if infants receive passive-active prophylaxis with HBV immunoglobulin (HBIg) and initiate the hepatitis B vaccine series at birth. We designed a study to assess the efficacy and safety of a short course of maternal tenofovir disoproxil fumarate (TDF) among women with a marker of high viral load for the prevention of MTCT of HBV. Methods: The study is a phase III, multicenter (17 sites in Thailand), placebo-controlled, double-blind, randomized 1: 1, two-arm clinical trial of TDF 300 mg once daily versus placebo among pregnant women from 28 weeks' gestation through 2-month post-partum. All infants receive HBIg at birth, and a hepatitis B (HB) vaccination series according to Thai guidelines: birth, and age 1, 2, 4 and 6 months. Participant women at study entry must be age >= 18 years, hepatitis B surface antigen (HBsAg) and e-antigen (HBeAg) positive, have alanine aminotransferase (ALT) level < 30 IU/L at screening (confirmed < 60 IU/L pre-entry), negative hepatitis C serology, creatinine clearance > 50 mL/min, and no history of anti-HBV antiviral treatment. The target sample size of 328 mother/infant pairs assumed 156 evaluable cases per arm to detect a >= 9 % difference in MTCT transmission (3 % experimental arm versus 12 % placebo arm) with 90 % power. Mothers and infants are followed until 12 months after delivery. The primary infant endpoint is detection of HBsAg, confirmed by detection of HBV DNA at six months of age. Secondary endpoints are maternal and infant adverse events, acute exacerbations of maternal hepatitis B disease (ALT > 300 IU/ L, defined as a "flare") following discontinuation of study treatment, infant HBV infection status and growth up to 12 months of age. Discussion: The results of this randomized trial will clarify the efficacy and safety of a short course of antiviral treatment to prevent mother-to-child transmission of HBV and inform international guidelines. C1 [Jourdain, Gonzague; Ngo-Giang-Huong, Nicole; Cressey, Tim R.; Salvadori, Nicolas; Decker, Luc] Inst Rech Dev IRD France, PHPT, UMI 174, 187-10 Changklan Rd, Chiang Mai 50100, Thailand. [Jourdain, Gonzague; Ngo-Giang-Huong, Nicole; Cressey, Tim R.; Salvadori, Nicolas; Decker, Luc; Sirirungsi, Wasna; Khamduang, Woottichai] Chiang Mai Univ, Fac Associated Med Sci, 110 Intawaroroj Rd, Chiang Mai 50200, Thailand. [Jourdain, Gonzague; Ngo-Giang-Huong, Nicole; Cressey, Tim R.] Harvard TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, 677 Huntington Ave, Boston, MA 02115 USA. [Cressey, Tim R.] Univ Liverpool, Inst Translat Med, Dept Mol & Clin Pharmacol, Liverpool, Merseyside, England. [Hua, Lei; Harrison, Linda; Tierney, Camlin] Harvard TH Chan Sch Publ Hlth, Ctr Biostat AIDS Res CBAR, 677 Huntington Ave, Boston, MA 02115 USA. [Bowonwatanuwong, Chureeratana; Chotivanich, Nantasak] Chonburi Hosp, 69 M-2,Sukhumvit Rd, Muang 20000, Chonburi, Thailand. [Puthanakit, Thanyawee] Chulalongkorn Univ, Fac Med, 1873 Rama 4 Rd, Bangkok 10330, Thailand. [Siberry, George K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, 6100 Execut Blvd, Bethesda, MD 20892 USA. [Watts, Diane Heather] US Dept State, Off Global AIDS Coordinator, SA-22,2201 C St NW, Washington, DC 20522 USA. [Murphy, Trudy V.] Ctr Dis Control & Prevent, DHHS CDC NCHHSTP DVH Vaccine Unit, Bldg Corp SQ 12,Room 3111, Atlanta, GA 30329 USA. [Achalapong, Jullapong] Chiangrai Prachanukroh Hosp, Dept Obstet & Gynecol, 1039 Sathan Phayaban Rd, Muang 57000, Chiang Rai, Thailand. [Hongsiriwon, Suchat] Chonburi Hosp, Dept Pediat, 69 M-2,Sukhumvit Rd, Muang 20000, Chonburi, Thailand. [Klinbuayaem, Virat] Sanpatong Hosp, Dept Med, 149 M-15 Yuhwa, Chiang Mai 50120, Thailand. [Traisathit, Patrinee] Chiang Mai Univ, Dept Stat, Fac Sci, 239 Huaykaew Rd, Chiang Mai 50200, Thailand. [Thongsawat, Satawat] Chiang Mai Univ, Dept Internal Med, Fac Med, Chiang Mai 50200, Thailand. [Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, GI Unit, WRN 1007C,55 Fruit St, Boston, MA 02114 USA. [Pol, Stanislas] Cochin Univ Hosp, Dept Hepatogastroenterol, 27 Rue Faubourg St Jacques, F-75679 Paris 14, France. RP Jourdain, G (reprint author), Inst Rech Dev IRD France, PHPT, UMI 174, 187-10 Changklan Rd, Chiang Mai 50100, Thailand.; Jourdain, G (reprint author), Chiang Mai Univ, Fac Associated Med Sci, 110 Intawaroroj Rd, Chiang Mai 50200, Thailand. EM gonzague.jourdain@ird.fr FU Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) [U01HD071889] FX The study activities are supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) (U01HD071889) under a cooperative agreement between NICHD, the Centers for Disease Control and Prevention, United States of America, and Institut de recherche pour le developpement, France. NR 12 TC 1 Z9 1 U1 8 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2334 J9 BMC INFECT DIS JI BMC Infect. Dis. PD AUG 9 PY 2016 VL 16 AR 393 DI 10.1186/s12879-016-1734-5 PG 6 WC Infectious Diseases SC Infectious Diseases GA DT2YM UT WOS:000381347700010 PM 27506549 ER PT J AU Joyce, BT Gao, T Zheng, YA Liu, L Zhang, W Dai, Q Shrubsole, MJ Hibler, EA Cristofanilli, M Zhang, H Yang, HS Vokonas, P Cantone, L Schwartz, J Baccarelli, A Hou, LF AF Joyce, Brian T. Gao, Tao Zheng, Yinan Liu, Lei Zhang, Wei Dai, Qi Shrubsole, Martha J. Hibler, Elizabeth A. Cristofanilli, Massimo Zhang, Hu Yang, Hushan Vokonas, Pantel Cantone, Laura Schwartz, Joel Baccarelli, Andrea Hou, Lifang TI Prospective changes in global DNA methylation and cancer incidence and mortality SO BRITISH JOURNAL OF CANCER LA English DT Article DE Global DNA methylation; cancer incidence; cancer mortality ID BLOOD LEUKOCYTE DNA; HEPATOCELLULAR-CARCINOMA; BLADDER-CANCER; GASTRIC-CANCER; BREAST-CANCER; REPETITIVE ELEMENTS; LINE-1 METHYLATION; COLORECTAL ADENOMA; PERIPHERAL-BLOOD; CELL DNA AB Background: Methylation of repetitive elements Alu and LINE-1 in humans is considered a surrogate for global DNA methylation. Previous studies of blood-measured Alu/LINE-1 and cancer risk are inconsistent. Methods: We studied 1259 prospective methylation measurements from blood drawn 1-4 times from 583 participants from 1999 to 2012. We used Cox regression to evaluate time-dependent methylation as a biomarker for cancer risk and mortality, and linear regression to compare mean differences in methylation over time by cancer status and analyse associations between rate of methylation change and cancer. Results: Time-dependent LINE-1 methylation was associated with prostate cancer incidence (HR: 1.38, 95% CI: 1.01-1.88) and all-cancer mortality (HR: 1.41, 95% CI: 1.03-1.92). The first measurement of Alu methylation (HR: 1.39, 95% CI: 1.08-1.79) was associated with all-cancer mortality. Participants who ultimately developed cancer had lower mean LINE-1 methylation than cancer-free participants 10+ years pre-diagnosis (P<0.01). Rate of Alu methylation change was associated with all-cancer incidence (HR: 3.62, 95% CI: 1.09-12.10). Conclusions: Our results add longitudinal data on blood Alu and LINE-1 methylation and cancer, and potentially contribute to their use as early-detection biomarkers. Future larger studies are needed and should account for the interval between blood sample collection and cancer diagnosis. C1 [Joyce, Brian T.; Gao, Tao; Zheng, Yinan; Liu, Lei; Zhang, Wei; Hibler, Elizabeth A.; Zhang, Hu; Hou, Lifang] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, 680 N Lake Shore Dr,Suite 1400, Chicago, IL 60611 USA. [Joyce, Brian T.] Univ Illinois, Sch Publ Hlth, Div Epidemiol Biostat, 1603 W Taylor St, Chicago, IL 60612 USA. [Zheng, Yinan] Northwestern Univ, Inst Publ Hlth & Med, Feinberg Sch Med, 680 N Lake Shore Dr,Suite 1400, Chicago, IL 60611 USA. [Dai, Qi; Shrubsole, Martha J.] Vanderbilt Univ, Med Ctr, 2525 West End Ave,Suite 319, Nashville, TN 37203 USA. [Cristofanilli, Massimo] Northwestern Univ, Feinberg Sch Med, Div Hematol Oncol, 676 N St Clair St,8th Floor, Chicago, IL 60611 USA. [Yang, Hushan] Thomas Jefferson Univ, Div Populat Sci, Dept Med Oncol, Sidney Kimmel Canc Ctr, 834 Chestnut St,Suite 314, Philadelphia, PA 19107 USA. [Vokonas, Pantel] VA Boston Healthcare Syst, VA Normat Aging Study, 150 South Huntington Ave, Boston, MA 02130 USA. [Vokonas, Pantel] Boston Univ, Dept Med, Sch Med, Boston, MA 02118 USA. [Cantone, Laura] Univ Milan, Dept Clin Sci & Community Hlth, Mol Epidemiol & Environm Epigenet Lab, San Barnaba 8, I-20122 Milan, Italy. [Schwartz, Joel; Baccarelli, Andrea] Harvard Sch Publ Hlth, Dept Environm Hlth, 655 Huntington Ave, Boston, MA 02115 USA. [Hou, Lifang] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, 303 E Chicago Ave,Olson Pavil 8350, Chicago, IL 60611 USA. RP Hou, LF (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, 680 N Lake Shore Dr,Suite 1400, Chicago, IL 60611 USA.; Hou, LF (reprint author), Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, 303 E Chicago Ave,Olson Pavil 8350, Chicago, IL 60611 USA. EM l-hou@northwestern.edu RI Liu, Lei/B-4968-2009; Zheng, Yinan/E-5775-2017; OI Liu, Lei/0000-0003-1844-338X; Cantone, Laura/0000-0003-3660-129X FU Ziff Fund at the Harvard University Center for the Environment, NIEHS grants [RO1-ES015172, 2RO1-ES015172, ES014663]; Cooperative Studies Program/Epidemiology Research and Information Center of the U.S. Department of Veterans Affairs; USEPA grant [RD-832416, RD-83479801]; Northwestern University Robert H. Lurie Comprehensive Cancer Center Rosenberg Research Fund; National Institute of Environmental Health Sciences [NIEHS R01-ES021733, NIEHS R01-ES015172, NIEHS P30-ES00002] FX This work was supported by the Ziff Fund at the Harvard University Center for the Environment, NIEHS grants RO1-ES015172, 2RO1-ES015172, and ES014663. The Normative Aging Study is supported by the Cooperative Studies Program/Epidemiology Research and Information Center of the U.S. Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center, Boston, MA, USA. In addition, this publication was made possible by USEPA grant RD-832416 and RD-83479801. LH received additional support from the Northwestern University Robert H. Lurie Comprehensive Cancer Center Rosenberg Research Fund. AB and JS received additional support from the National Institute of Environmental Health Sciences (NIEHS R01-ES021733, NIEHS R01-ES015172, and NIEHS P30-ES00002). NR 48 TC 0 Z9 0 U1 3 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD AUG 9 PY 2016 VL 115 IS 4 BP 465 EP 472 DI 10.1038/bjc.2016.205 PG 8 WC Oncology SC Oncology GA DT2HZ UT WOS:000381302700009 PM 27351216 ER PT J AU Killian, NJ Watkins, PV Davidson, LS Barbour, DL AF Killian, Nathan J. Watkins, Paul V. Davidson, Lisa S. Barbour, Dennis L. TI The Effects of Auditory Contrast Tuning upon Speech Intelligibility SO FRONTIERS IN PSYCHOLOGY LA English DT Article DE auditory cortex; noise reduction; human; cochlear implant; primate ID HEARING-IMPAIRED LISTENERS; COCHLEAR IMPLANT LISTENERS; MINIMUM SPECTRAL CONTRAST; FREQUENCY-SELECTIVITY; VOWEL IDENTIFICATION; ACOUSTIC HEARING; NOISE; ENHANCEMENT; RECOGNITION; RESOLUTION AB We have previously identified neurons tuned to spectral contrast of wideband sounds in auditory cortex of awake marmoset monkeys. Because additive noise alters the spectral contrast of speech, contrast-tuned neurons, if present in human auditory cortex, may aid in extracting speech from noise. Given that this cortical function may be underdeveloped in individuals with sensorineural hearing loss, incorporating biologically-inspired algorithms into external signal processing devices could provide speech enhancement benefits to cochlear implantees. In this study we first constructed a computational signal processing algorithm to mimic auditory cortex contrast tuning. We then manipulated the shape of contrast channels and evaluated the intelligibility of reconstructed noisy speech using a metric to predict cochlear implant user perception. Candidate speech enhancement strategies were then tested in cochlear implantees with a hearing-in-noise test. Accentuation of intermediate contrast values or all contrast values improved computed intelligibility. Cochlear implant subjects showed significant improvement in noisy speech intelligibility with a contrast shaping procedure. C1 [Killian, Nathan J.; Watkins, Paul V.; Barbour, Dennis L.] Washington Univ, Dept Biomed Engn, Lab Sensory Neurosci & Neuroengn, St Louis, MO 63130 USA. [Davidson, Lisa S.] Washington Univ, Sch Med, Cent Inst Deaf, St Louis, MO USA. [Killian, Nathan J.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Watkins, Paul V.] Global Solut Network Inc, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. RP Barbour, DL (reprint author), Washington Univ, Dept Biomed Engn, Lab Sensory Neurosci & Neuroengn, St Louis, MO 63130 USA. EM dbarbour@wustl.edu FU Wallace H. Coulter Foundation; National Institutes of health [R01-DC009215]; Center for Integration of Medicine and Innovative Technology FX Supported by The Wallace H. Coulter Foundation and National Institutes of health grant R01-DC009215 and The Center for Integration of Medicine and Innovative Technology. NR 39 TC 0 Z9 0 U1 0 U2 0 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-1078 J9 FRONT PSYCHOL JI Front. Psychol. PD AUG 9 PY 2016 VL 7 AR 1145 DI 10.3389/fpsyg.2076.07745 PG 16 WC Psychology, Multidisciplinary SC Psychology GA DS7WB UT WOS:000380992500002 PM 27555826 ER PT J AU Bibbins-Domingo, K Grossman, DC Curry, SJ Davidson, KW Epling, JW Garcia, FAR Gillman, MW Kemper, AR Krist, AH Kurth, AE Landefeld, CS LeFevre, M Mangione, CM Phillips, WR Phipps, MG Pignone, MP Siu, AL AF Bibbins-Domingo, Kirsten Grossman, David C. Curry, Susan J. Davidson, Karina W. Epling, John W., Jr. Garcia, Francisco A. R. Gillman, Matthew W. Kemper, Alex R. Krist, Alex H. Kurth, Ann E. Landefeld, C. Seth LeFevre, Michael Mangione, Carol M. Phillips, William R. Phipps, Maureen G. Pignone, Michael P. Siu, Albert L. CA US Preventive Serv Task Force TI Screening for Lipid Disorders in Children and Adolescents US Preventive Services Task Force Recommendation Statement SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID FAMILIAL HYPERCHOLESTEROLEMIA; BLOOD; DYSLIPIDEMIA; PREVALENCE; CHILDHOOD; THERAPY; DISEASE; TRENDS; RISK AB IMPORTANCE Elevations in levels of total, low-density lipoprotein, and non-high-density lipoprotein cholesterol; lower levels of high-density lipoprotein cholesterol; and, to a lesser extent, elevated triglyceride levels are associated with risk of cardiovascular disease in adults. OBJECTIVE To update the 2007 US Preventive Services Task Force (USPSTF) recommendation on screening for lipid disorders in children, adolescents, and young adults. EVIDENCE REVIEW The USPSTF reviewed the evidence on screening for lipid disorders in children and adolescents 20 years or younger-1 review focused on screening for heterozygous familial hypercholesterolemia, and 1 review focused on screening for multifactorial dyslipidemia. FINDINGS Evidence on the quantitative difference in diagnostic yield between universal and selective screening approaches, the effectiveness and harms of long-term treatment and the harms of screening, and the association between changes in intermediate outcomes and improvements in adult cardiovascular health outcomes are limited. Therefore, the USPSTF concludes that the balance of benefits and harms cannot be determined. CONCLUSIONS AND RECOMMENDATION The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for lipid disorders in children and adolescents 20 years or younger. (I statement) C1 [Bibbins-Domingo, Kirsten] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Grossman, David C.] Grp Hlth Res Inst, Seattle, WA USA. [Curry, Susan J.] Univ Iowa, Iowa City, IA USA. [Davidson, Karina W.] Columbia Univ, New York, NY USA. [Epling, John W., Jr.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. [Garcia, Francisco A. R.] Pima Cty Dept Hlth, Tucson, AZ USA. [Gillman, Matthew W.] Harvard Med Sch, Boston, MA USA. [Gillman, Matthew W.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Kemper, Alex R.] Duke Univ, Durham, NC USA. [Krist, Alex H.] Fairfax Family Practice Residency, Fairfax, VA USA. [Krist, Alex H.] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Kurth, Ann E.] Yale Univ, New Haven, CT USA. [Landefeld, C. Seth] Univ Alabama Birmingham, Birmingham, AL USA. [LeFevre, Michael] Univ Missouri, Columbia, MO 65211 USA. [Mangione, Carol M.] Univ Calif Los Angeles, Los Angeles, CA USA. [Phillips, William R.] Univ Washington, Seattle, WA 98195 USA. [Phipps, Maureen G.] Brown Univ, Providence, RI 02912 USA. [Pignone, Michael P.] Univ Texas Austin, Austin, TX 78712 USA. [Siu, Albert L.] Mt Sinai Sch Med, New York, NY USA. [Siu, Albert L.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Bibbins-Domingo, K (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. OI Epling, John W/0000-0001-9445-8669 FU Agency for Healthcare Research and Quality (AHRQ) FX The USPSTF is an independent, voluntary body. The US Congress mandates that the Agency for Healthcare Research and Quality (AHRQ) support the operations of the USPSTF. NR 32 TC 3 Z9 3 U1 3 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 AUG 9 PY 2016 VL 316 IS 6 BP 625 EP 633 DI 10.1001/jama.2016.9852 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA DS7TK UT WOS:000380985600015 ER PT J AU Liang, SH Chen, JM Normandin, MD Chang, JS Chang, GC Taylor, CK Trapa, P Plummer, MS Para, KS Conn, EL Lopresti-Morrow, L Lanyon, LF Cook, JM Richter, KEG Nolan, CE Schachter, JB Janat, F Che, Y Shanmugasundaram, V Lefker, BA Enerson, BE Livni, E Wang, L Guehl, NJ Patnaik, D Wagner, FF Perlis, R Holson, EB Haggarty, SJ El Fakhri, G Kurumbail, RG Vasdev, N AF Liang, Steven H. Chen, Jinshan Michael Normandin, Marc D. Chang, Jeanne S. Chang, George C. Taylor, Christine K. Trapa, Patrick Plummer, Mark S. Para, Kimberly S. Conn, Edward L. Lopresti-Morrow, Lori Lanyon, Lorraine F. Cook, James M. Richter, Karl E. G. Nolan, Charlie E. Schachter, Joel B. Janat, Fouad Che, Ye Shanmugasundaram, Veerabahu Lefker, Bruce A. Enerson, Bradley E. Livni, Elijahu Wang, Lu Guehl, Nicolas J. Patnaik, Debasis Wagner, Florence F. Perlis, Roy Holson, Edward B. Haggarty, Stephen J. El Fakhri, Georges Kurumbail, Ravi G. Vasdev, Neil TI Discovery of a Highly Selective Glycogen Synthase Kinase-3 Inhibitor (PF-04802367) That Modulates Tau Phosphorylation in the Brain: Translation for PET Neuroimaging SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE Alzheimer's disease; glycogen synthase kinase-3; phosphorylation; positron emission tomography; tau proteins ID ALZHEIMERS-DISEASE; TRANSGENIC MICE; GSK-3-BETA; RADIOSYNTHESIS; RADIOTRACER; VIVO AB Glycogen synthase kinase-3 (GSK-3) regulates multiple cellular processes in diabetes, oncology, and neurology. N-(3-(1H-1,2,4-triazol-1-yl)propyl)-5-(3-chloro-4-methoxyphenyl)oxazole-4-carboxamide (PF-04802367 or PF367) has been identified as a highly potent inhibitor, which is among the most selective antagonists of GSK-3 to date. Its efficacy was demonstrated in modulation of tau phosphorylation in vitro and in vivo. Whereas the kinetics of PF-367 binding in brain tissues are too fast for an effective therapeutic agent, the pharmacokinetic profile of PF-367 is ideal for discovery of radiopharmaceuticals for GSK-3 in the central nervous system. A C-11-isotopologue of PF-367 was synthesized and preliminary PET imaging studies in non-human primates confirmed that we have overcome the two major obstacles for imaging GSK-3, namely, reasonable brain permeability and displaceable binding. C1 [Liang, Steven H.; Normandin, Marc D.; Livni, Elijahu; Wang, Lu; Guehl, Nicolas J.; El Fakhri, Georges; Vasdev, Neil] Massachusetts Gen Hosp, Gordon Ctr Med Imaging & Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Liang, Steven H.; Normandin, Marc D.; Livni, Elijahu; Wang, Lu; Guehl, Nicolas J.; El Fakhri, Georges; Vasdev, Neil] Harvard Med Sch, Dept Radiol, Boston, MA 02114 USA. [Chen, Jinshan Michael; Chang, Jeanne S.; Chang, George C.; Taylor, Christine K.; Plummer, Mark S.; Para, Kimberly S.; Conn, Edward L.; Lopresti-Morrow, Lori; Lanyon, Lorraine F.; Cook, James M.; Richter, Karl E. G.; Nolan, Charlie E.; Schachter, Joel B.; Janat, Fouad; Che, Ye; Shanmugasundaram, Veerabahu; Enerson, Bradley E.; Kurumbail, Ravi G.] Pfizer Worldwide Res & Dev, Groton Labs, Eastern Point Rd, Groton, CT 06340 USA. [Trapa, Patrick; Lefker, Bruce A.] Pfizer Worldwide Res & Dev, 610 Main St, Cambridge, MA 02139 USA. [Wagner, Florence F.; Perlis, Roy; Holson, Edward B.] Broad Inst, Stanley Ctr Psychiat Res, 415 Main St, Cambridge, MA 02142 USA. [Patnaik, Debasis; Perlis, Roy; Haggarty, Stephen J.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, 185 Cambridge St, Boston, MA 02114 USA. [Patnaik, Debasis; Perlis, Roy; Haggarty, Stephen J.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, 185 Cambridge St, Boston, MA 02114 USA. RP Vasdev, N (reprint author), Massachusetts Gen Hosp, Gordon Ctr Med Imaging & Nucl Med & Mol Imaging, Boston, MA 02114 USA.; Vasdev, N (reprint author), Harvard Med Sch, Dept Radiol, Boston, MA 02114 USA.; Kurumbail, RG (reprint author), Pfizer Worldwide Res & Dev, Groton Labs, Eastern Point Rd, Groton, CT 06340 USA. EM ravi.g.kurumbail@pfizer.com; vasdev.neil@mgh.harvard.edu OI Patnaik, Debasis/0000-0002-9829-3352 FU Hauptman-Woodward Medical Research Institute; IMCA-CAT at Advanced Photon Source, U.S. Department of Energy [DE-AC02-06CH11357]; NIH [NIDA 1K01DA038000]; Tau Consortium FX We thank Rebecca Lewis, Justin Pine, Patricia Cosgrove, Jeffrey Asbill, Dr. Dustin Wooten, Dr. T. Lee Collier, and Dr. Lee Josephson for technical support and helpful discussions. We thank Seungil Han, Mark Ammirati, Mathew Calabrese, Jayvardhan Pandit, and Mathew Griffor for crystallographic studies, supported by Hauptman-Woodward Medical Research Institute and IMCA-CAT at Advanced Photon Source, U.S. Department of Energy (DE-AC02-06CH11357). S.H.L. is a recipient of an NIH career development award (NIDA 1K01DA038000). S.J.H. was supported in part by the Tau Consortium. NR 32 TC 2 Z9 2 U1 6 U2 6 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 101161, 69451 WEINHEIM, GERMANY SN 1433-7851 EI 1521-3773 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PD AUG 8 PY 2016 VL 55 IS 33 BP 9600 EP 9604 DI 10.1002/anie.201603797 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA DW0ZQ UT WOS:000383372700023 PM 27355874 ER PT J AU Yetisen, AK Montelongo, Y Butt, H AF Yetisen, Ali K. Montelongo, Yunuen Butt, Haider TI Rewritable three-dimensional holographic data storage via optical forces SO APPLIED PHYSICS LETTERS LA English DT Article ID PHOTONIC CRYSTAL SENSORS; LASER-ABLATION; NANOSTRUCTURES; NANOSENSOR AB The development of nanostructures that can be reversibly arranged and assembled into 3D patterns may enable optical tunability. However, current dynamic recording materials such as photorefractive polymers cannot be used to store information permanently while also retaining configurability. Here, we describe the synthesis and optimization of a silver nanoparticle doped poly(2-hydroxyethyl methacrylate-co-methacrylic acid) recording medium for reversibly recording 3D holograms. We theoretically and experimentally demonstrate organizing nanoparticles into 3D assemblies in the recording medium using optical forces produced by the gradients of standing waves. The nanoparticles in the recording medium are organized by multiple nanosecond laser pulses to produce reconfigurable slanted multilayer structures. We demonstrate the capability of producing rewritable optical elements such as multilayer Bragg diffraction gratings, 1D photonic crystals, and 3D multiplexed optical gratings. We also show that 3D virtual holograms can be reversibly recorded. This recording strategy may have applications in reconfigurable optical elements, data storage devices, and dynamic holographic displays. Published by AIP Publishing. C1 [Yetisen, Ali K.] Harvard Med Sch, 65 Landsdowne St, Cambridge, MA 02139 USA. [Yetisen, Ali K.] Massachusetts Gen Hosp, Wellman Ctr Photomed, 65 Landsdowne St, Cambridge, MA 02139 USA. [Yetisen, Ali K.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Montelongo, Yunuen] Imperial Coll London, Dept Chem, South Kensington Campus, London SW7 2AZ, England. [Butt, Haider] Univ Birmingham, Sch Engn Sci, Nanotechnol Lab, Birmingham B15 2TT, W Midlands, England. RP Yetisen, AK (reprint author), Harvard Med Sch, 65 Landsdowne St, Cambridge, MA 02139 USA.; Yetisen, AK (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 65 Landsdowne St, Cambridge, MA 02139 USA.; Yetisen, AK (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM ayetisen@mgh.harvard.edu OI Butt, Haider/0000-0003-2434-9525 FU Leverhulme Trust FX The authors thank the Leverhulme Trust for research funding. NR 23 TC 1 Z9 1 U1 24 U2 24 PU AMER INST PHYSICS PI MELVILLE PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA SN 0003-6951 EI 1077-3118 J9 APPL PHYS LETT JI Appl. Phys. Lett. PD AUG 8 PY 2016 VL 109 IS 6 AR 061106 DI 10.1063/1.4960710 PG 5 WC Physics, Applied SC Physics GA DV8JP UT WOS:000383183600006 ER PT J AU Berger, AH Brooks, AN Wu, XY Shrestha, Y Chouinard, C Piccioni, F Bagul, M Kamburov, A Imielinski, M Hogstrom, L Zhu, C Yang, XP Pantel, S Sakai, R Watson, J Kaplan, N Campbell, JD Singh, S Root, DE Narayan, R Natoli, T Lahr, DL Tirosh, I Tamayo, P Getz, G Wong, B Doench, J Subramanian, A Golub, TR Meyerson, M Boehm, JS AF Berger, Alice H. Brooks, Angela N. Wu, Xiaoyun Shrestha, Yashaswi Chouinard, Candace Piccioni, Federica Bagul, Mukta Kamburov, Atanas Imielinski, Marcin Hogstrom, Larson Zhu, Cong Yang, Xiaoping Pantel, Sasha Sakai, Ryo Watson, Jacqueline Kaplan, Nathan Campbell, Joshua D. Singh, Shantanu Root, David E. Narayan, Rajiv Natoli, Ted Lahr, David L. Tirosh, Itay Tamayo, Pablo Getz, Gad Wong, Bang Doench, John Subramanian, Aravind Golub, Todd R. Meyerson, Matthew Boehm, Jesse S. TI High-throughput Phenotyping of Lung Cancer Somatic Mutations SO CANCER CELL LA English DT Article ID RNA INTERFERENCE SCREEN; TUMOR SAMPLES; LIVER-CANCER; HUMAN-CELLS; GENOME; GENES; IDENTIFICATION; ADENOCARCINOMA; INHIBITION; GEFITINIB AB Recent genome sequencing efforts have identified millions of somatic mutations in cancer. However, the functional impact of most variants is poorly understood. Here we characterize 194 somatic mutations identified in primary lung adenocarcinomas. We present an expression-based variant-impact phenotyping (eVIP) method that uses gene expression changes to distinguish impactful from neutral somatic mutations. eVIP identified 69% of mutations analyzed as impactful and 31% as functionally neutral. A subset of the impactful mutations induces xenograft tumor formation in mice and/or confers resistance to cellular EGFR inhibition. Among these impactful variants are rare somatic, clinically actionable variants including EGFR S645C, ARAF S214C and S214F, ERBB2 S418T, and multiple BRAF variants, demonstrating that rare mutations can be functionally important in cancer. C1 [Berger, Alice H.; Brooks, Angela N.; Imielinski, Marcin; Watson, Jacqueline; Kaplan, Nathan; Campbell, Joshua D.; Golub, Todd R.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Berger, Alice H.; Brooks, Angela N.; Wu, Xiaoyun; Shrestha, Yashaswi; Chouinard, Candace; Kamburov, Atanas; Imielinski, Marcin; Hogstrom, Larson; Watson, Jacqueline; Campbell, Joshua D.; Narayan, Rajiv; Natoli, Ted; Lahr, David L.; Tamayo, Pablo; Getz, Gad; Wong, Bang; Subramanian, Aravind; Golub, Todd R.; Meyerson, Matthew; Boehm, Jesse S.] Broad Inst MIT & Harvard, Canc Program, Cambridge, MA 02142 USA. [Berger, Alice H.; Brooks, Angela N.; Kamburov, Atanas; Imielinski, Marcin; Campbell, Joshua D.; Getz, Gad; Meyerson, Matthew] Harvard Med Sch, Dept Pathol, Boston, MA 02115 USA. [Piccioni, Federica; Bagul, Mukta; Zhu, Cong; Yang, Xiaoping; Pantel, Sasha; Root, David E.; Doench, John] Broad Inst MIT & Harvard, Genet Perturbat Platform, Cambridge, MA 02142 USA. [Kamburov, Atanas; Getz, Gad] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kamburov, Atanas; Getz, Gad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Sakai, Ryo] Katholieke Univ Leuven, Dept Elect Engn ESAT STADIUS, B-3000 Leuven, Belgium. [Singh, Shantanu] Broad Inst MIT & Harvard, Imaging Platform, Cambridge, MA 02142 USA. [Tirosh, Itay] Broad Inst MIT & Harvard, Cell Circuits & Epigen Program, Cambridge, MA 02142 USA. [Golub, Todd R.] Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA. [Brooks, Angela N.] Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA. RP Meyerson, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.; Meyerson, M; Boehm, JS (reprint author), Broad Inst MIT & Harvard, Canc Program, Cambridge, MA 02142 USA.; Meyerson, M (reprint author), Harvard Med Sch, Dept Pathol, Boston, MA 02115 USA. EM matthew_meyerson@dfci.harvard.edu; boehm@broadinstitute.org OI Doench, John/0000-0002-3707-9889 FU Carlos Slim Foundation in Mexico; National Cancer Institute [1R35CA197568]; American Cancer Society [122398-PF-12-080-01-TBG]; National Cancer Institute Pathway to Independence award [K99CA197762] FX We thank members of the Meyerson and Golub labs for critical advice and discussion. We thank Iris Fung for graphic design of the graphical abstract. We thank Heidi Greulich and Tanaz Sharifnia for reagents and advice. We are grateful for the feedback and advice from Anne Carpenter, Eejung Kim, Nina Ilic, Lihua Zou, William Kim, Cory Johannessen, Steven Corsello, and William Hahn. The work was conducted as part of the Slim Initiative for Genomic Medicine, a project funded by the Carlos Slim Foundation in Mexico, with additional support of National Cancer Institute grant 1R35CA197568 and an American Cancer Society Research Professorship to M.M., an American Cancer Society Postdoctoral Research Fellowship (122398-PF-12-080-01-TBG) and a National Cancer Institute Pathway to Independence award (K99CA197762) to A.H.B. A.N.B was a Merck Fellow of the Damon Runyon Cancer Research Foundation (DRG-2138-12). T.R.G. and M.M. are founders and equity holders of Foundation Medicine, a for-profit company that provides next-generation sequencing diagnostic services. NR 47 TC 5 Z9 5 U1 4 U2 6 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 AUG 8 PY 2016 VL 30 IS 2 BP 214 EP 228 DI 10.1016/j.ccell.2016.06.022 PG 15 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DT2AC UT WOS:000381282200007 PM 27478040 ER PT J AU Miranda, F Mannion, D Liu, SJ Zheng, YY Mangala, LS Redondo, C Herrero-Gonzalez, S Xu, RY Taylor, C Chedom, DF Karaminejadranjbar, M Albukhari, A Jiang, DH Pradeep, S Rodriguez-Aguayo, C Lopez-Berestein, G Salah, E Azeez, KRA Elkins, JM Campo, L Myers, KA Klotz, D Bivona, S Dhar, S Bast, RC Saya, H Choi, HG Gray, NS Fischer, R Kessler, BM Yau, C Sood, AK Motohara, T Knapp, S Ahmed, AA AF Miranda, Fabrizio Mannion, David Liu, Shujuan Zheng, Yiyan Mangala, Lingegowda S. Redondo, Clara Herrero-Gonzalez, Sandra Xu, Ruoyan Taylor, Charlotte Chedom, Donatien Fotso Karaminejadranjbar, Mohammad Albukhari, Ashwag Jiang, Dahai Pradeep, Sunila Rodriguez-Aguayo, Cristian Lopez-Berestein, Gabriel Salah, Eidarus Azeez, Kamal R. Abdul Elkins, Jonathan M. Campo, Leticia Myers, Kevin A. Klotz, Daniel Bivona, Serena Dhar, Sunanda Bast, Robert C., Jr. Saya, Hideyuki Choi, Hwan Geun Gray, Nathanael S. Fischer, Roman Kessler, Benedikt M. Yau, Christopher Sood, Anil K. Motohara, Takeshi Knapp, Stefan Ahmed, Ahmed Ashour TI Salt-Inducible Kinase 2 Couples Ovarian Cancer Cell Metabolism with Survival at the Adipocyte-Rich Metastatic Niche SO CANCER CELL LA English DT Article ID ACTIVATED PROTEIN-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; TUMOR MICROENVIRONMENT; SIGNALING CASCADE; PHOSPHORYLATION; SIK2; P85; EXPRESSION; GLUCONEOGENESIS; IDENTIFICATION AB The adipocyte-rich microenvironment forms a niche for ovarian cancer metastasis, but the mechanisms driving this process are incompletely understood. Here we show that salt-inducible kinase 2 (SIK2) is over-expressed in adipocyte-rich metastatic deposits compared with ovarian primary lesions. Overexpression of SIK2 in ovarian cancer cells promotes abdominal metastasis while SIK2 depletion prevents metastasis in vivo. Importantly, adipocytes induce calcium-dependent activation and autophosphorylation of SIK2. Activated SIK2 plays a dual role in augmenting AMPK-induced phosphorylation of acetyl-CoA carboxylase and in activating the PI3K/AKT pathway through p85 alpha-S154 phosphorylation. These findings identify SIK2 at the apex of the adipocyte-induced signaling cascades in cancer cells and make a compelling case for targeting SIK2 for therapy in ovarian cancer. C1 [Miranda, Fabrizio; Mannion, David; Liu, Shujuan; Zheng, Yiyan; Redondo, Clara; Herrero-Gonzalez, Sandra; Xu, Ruoyan; Taylor, Charlotte; Chedom, Donatien Fotso; Karaminejadranjbar, Mohammad; Albukhari, Ashwag; Klotz, Daniel; Bivona, Serena; Ahmed, Ahmed Ashour] Univ Oxford, Weatherall Inst Mol Med, Ovarian Canc Cell Lab, Oxford OX3 9DS, England. [Miranda, Fabrizio; Mannion, David; Liu, Shujuan; Zheng, Yiyan; Redondo, Clara; Herrero-Gonzalez, Sandra; Xu, Ruoyan; Taylor, Charlotte; Chedom, Donatien Fotso; Karaminejadranjbar, Mohammad; Albukhari, Ashwag; Klotz, Daniel; Bivona, Serena; Ahmed, Ahmed Ashour] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Obstet & Gynaecol, Womens Ctr, Oxford OX3 9DU, England. [Mangala, Lingegowda S.; Jiang, Dahai; Pradeep, Sunila; Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Gynecol Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA. [Mangala, Lingegowda S.; Jiang, Dahai; Rodriguez-Aguayo, Cristian; Lopez-Berestein, Gabriel; Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Ctr RNAi & Noncoding RNA, 1515 Holcombe Blvd, Houston, TX 77030 USA. [Redondo, Clara; Salah, Eidarus; Azeez, Kamal R. Abdul; Elkins, Jonathan M.; Knapp, Stefan] Univ Oxford, Nuffield Dept Med, Struct Genom Consortium, Old Rd Campus Res Bldg, Oxford OX3 7DQ, England. [Albukhari, Ashwag] King Abdulaziz Univ, Dept Biochem, Fac Sci, Jeddah 21551, Saudi Arabia. [Rodriguez-Aguayo, Cristian; Lopez-Berestein, Gabriel; Bast, Robert C., Jr.] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. [Campo, Leticia; Myers, Kevin A.] Univ Oxford, Dept Oncol, Old Rd Campus Res Bldg,Roosevelt Dr, Oxford OX3 7DQ, England. [Dhar, Sunanda] Oxford Univ Hosp, Dept Histopathol, Oxford OX3 9DU, England. [Saya, Hideyuki] Keio Univ, Inst Adv Med Res, Sch Med, Div Gene Regulat, Tokyo 1608582, Japan. [Choi, Hwan Geun; Gray, Nathanael S.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Choi, Hwan Geun; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Fischer, Roman; Kessler, Benedikt M.; Knapp, Stefan] Univ Oxford, Target Discovery Inst, Nuffield Dept Med, Oxford OX3 7FZ, England. [Yau, Christopher] NIHR Biomed Res Ctr, Wellcome Trust Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England. [Yau, Christopher] Univ Oxford, Dept Stat, 1 South Pk Rd, Oxford OX1 3TG, England. [Motohara, Takeshi] Kumamoto Univ, Fac Life Sci, Dept Obstet & Gynecol, Kumamoto 8608556, Japan. [Knapp, Stefan] Goethe Univ Frankfurt, Inst Pharmaceut Chem, Riedberg Campus, D-60438 Frankfurt, Germany. [Knapp, Stefan] Buchmann Inst Life Sci, D-60438 Frankfurt, Germany. RP Ahmed, AA (reprint author), Univ Oxford, Weatherall Inst Mol Med, Ovarian Canc Cell Lab, Oxford OX3 9DS, England.; Ahmed, AA (reprint author), Univ Oxford, John Radcliffe Hosp, Nuffield Dept Obstet & Gynaecol, Womens Ctr, Oxford OX3 9DU, England. EM ahmed.ahmed@obs-gyn.ox.ac.uk RI Fachbereich14, Dekanat/C-8553-2015; Bast, Robert/E-6585-2011; OI Bast, Robert/0000-0003-4621-8462; Fischer, Roman/0000-0002-9715-5951; Knapp, Stefan/0000-0001-5995-6494; Kessler, Benedikt/0000-0002-8160-2446; Yau, Christopher/0000-0001-7615-8523 FU Medical Research Council; Ovarian Cancer Action; Oxford Biomedical Research Center; National Institute for Health Research; Cancer Research UK; Experimental Cancer Medicine Center; Helen Clarke Fund; Target Ovarian Cancer; NIH [UH3TR000943, P50 CA083639]; RGK Foundation; MRC New Investigator Research Grant [MR/L001411/1]; Wellcome Trust [090532/Z/09/Z, 092809/Z/10/Z]; SGC [1097737]; AbbVie; Bayer Pharma AG; Boehringer Ingelheim; Canada Foundation for Innovation; Genome Canada; GlaxoSmithKline; Janssen; Lilly Canada; Novartis Research Foundation; Ontario Ministry of Economic Development and Innovation; Pfizer; Takeda FX We thank the Gynecological Oncology Multidisciplinary Team at Oxford for help in recruiting patients, the Oxford Center for Histopathology Research for their technical work, and Fulvio Miranda, Karl Morten, and Matteo Morotti for helpful discussions. This work was funded by the Medical Research Council, Ovarian Cancer Action, Oxford Biomedical Research Center, the National Institute for Health Research, Cancer Research UK, Experimental Cancer Medicine Center, Helen Clarke Fund, Target Ovarian Cancer, NIH (UH3TR000943, P50 CA083639), and RGK Foundation. C.Y. acknowledges the support of an MRC New Investigator Research Grant (Ref. No. MR/L001411/1) and the Wellcome Trust Core Award Grant Number 090532/Z/09/Z. S.K. and C.R. are supported by the SGC, a registered charity (number 1097737) that receives funds from AbbVie, Bayer Pharma AG, Boehringer Ingelheim, the Canada Foundation for Innovation, Genome Canada, GlaxoSmithKline, Janssen, Lilly Canada, the Novartis Research Foundation, the Ontario Ministry of Economic Development and Innovation, Pfizer, Takeda, and the Wellcome Trust [092809/Z/10/Z]. NR 44 TC 2 Z9 2 U1 7 U2 10 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 AUG 8 PY 2016 VL 30 IS 2 BP 273 EP 289 DI 10.1016/j.ccell.2016.06.020 PG 17 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DT2AC UT WOS:000381282200011 PM 27478041 ER PT J AU Inoue, S Li, WDY Tseng, A Beerman, I Elia, AJ Bendall, SC Lemonnier, F Kron, KJ Cescon, DW Hao, ZY Lind, EF Takayama, N Planello, AC Shen, SY Shih, AH Larsen, DM Li, QX Snow, BE Wakeham, A Haight, J Gorrini, C Bassi, C Thu, KL Murakami, K Elford, AR Ueda, T Straley, K Yen, KE Melino, G Cimmino, L Aifantis, I Levine, RL De Carvalho, DD Lupien, M Rossi, DJ Nolan, GP Cairns, RA Mak, TW AF Inoue, Satoshi Li, Wanda Y. Tseng, Alan Beerman, Isabel Elia, Andrew J. Bendall, Sean C. Lemonnier, Francois Kron, Ken J. Cescon, David W. Hao, Zhenyue Lind, Evan F. Takayama, Naoya Planello, Aline C. Shen, Shu Yi Shih, Alan H. Larsen, Dana M. Li, Qinxi Snow, Bryan E. Wakeham, Andrew Haight, Jillian Gorrini, Chiara Bassi, Christian Thu, Kelsie L. Murakami, Kiichi Elford, Alisha R. Ueda, Takeshi Straley, Kimberly Yen, Katharine E. Melino, Gerry Cimmino, Luisa Aifantis, Iannis Levine, Ross L. De Carvalho, Daniel D. Lupien, Mathieu Rossi, Derrick J. Nolan, Garry P. Cairns, Rob A. Mak, Tak W. TI Mutant IDH1 Downregulates ATM and Alters DNA Repair and Sensitivity to DNA Damage Independent of TET2 SO CANCER CELL LA English DT Article ID HEMATOPOIETIC STEM-CELLS; ACUTE MYELOID-LEUKEMIA; SELF-RENEWAL; ATAXIA-TELANGIECTASIA; EPIGENETIC REGULATORS; OXIDATIVE STRESS; MUTATIONS; MICE; DIFFERENTIATION; CANCER AB Mutations in the isocitrate dehydrogenase-1 gene (IDH1) are common drivers of acute myeloid leukemia (AML) but their mechanism is not fully understood. It is thought that IDH1 mutants act by inhibiting TET2 to alter DNA methylation, but there are significant unexplained clinical differences between IDH1- and TET2-mutant diseases. We have discovered that mice expressing endogenous mutant IDH1 have reduced numbers of hematopoietic stem cells (HSCs), in contrast to Tet2 knockout (TET2-KO) mice. Mutant IDH1 downregulates the DNA damage (DD) sensor ATM by altering histone methylation, leading to impaired DNA repair, increased sensitivity to DD, and reduced HSC self-renewal, independent of TET2. ATM expression is also decreased in human IDH1-mutated AML. These findings may have implications for treatment of IDH-mutant leukemia. C1 [Inoue, Satoshi; Li, Wanda Y.; Tseng, Alan; Elia, Andrew J.; Lemonnier, Francois; Cescon, David W.; Hao, Zhenyue; Lind, Evan F.; Li, Qinxi; Snow, Bryan E.; Wakeham, Andrew; Haight, Jillian; Gorrini, Chiara; Bassi, Christian; Thu, Kelsie L.; Murakami, Kiichi; Elford, Alisha R.; Ueda, Takeshi; Cairns, Rob A.; Mak, Tak W.] Univ Hlth Network, Campbell Family Inst Breast Canc Res, Toronto, ON M5G 2C1, Canada. [Inoue, Satoshi; Li, Wanda Y.; Tseng, Alan; Elia, Andrew J.; Lemonnier, Francois; Kron, Ken J.; Cescon, David W.; Hao, Zhenyue; Lind, Evan F.; Takayama, Naoya; Planello, Aline C.; Shen, Shu Yi; Li, Qinxi; Snow, Bryan E.; Wakeham, Andrew; Haight, Jillian; Gorrini, Chiara; Bassi, Christian; Thu, Kelsie L.; Murakami, Kiichi; Elford, Alisha R.; De Carvalho, Daniel D.; Lupien, Mathieu; Cairns, Rob A.; Mak, Tak W.] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 1L7, Canada. [Inoue, Satoshi; Li, Wanda Y.; Tseng, Alan; Elia, Andrew J.; Lemonnier, Francois; Kron, Ken J.; Cescon, David W.; Hao, Zhenyue; Lind, Evan F.; Takayama, Naoya; Planello, Aline C.; Shen, Shu Yi; Li, Qinxi; Snow, Bryan E.; Wakeham, Andrew; Haight, Jillian; Gorrini, Chiara; Bassi, Christian; Thu, Kelsie L.; Murakami, Kiichi; Elford, Alisha R.; De Carvalho, Daniel D.; Lupien, Mathieu; Cairns, Rob A.; Mak, Tak W.] Univ Hlth Network, Ontario Canc Inst, Toronto, ON M5G 1L7, Canada. [Tseng, Alan; Kron, Ken J.; Planello, Aline C.; Shen, Shu Yi; De Carvalho, Daniel D.; Lupien, Mathieu; Mak, Tak W.] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada. [Beerman, Isabel; Rossi, Derrick J.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02133 USA. [Beerman, Isabel] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Bendall, Sean C.] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA. [Planello, Aline C.] Univ Estadual Campinas, Piracicaba Dent Sch, Dept Morphol, BR-13414903 Piracicaba, SP, Brazil. [Shih, Alan H.; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, Human Oncol & Pathogenesis Program, New York, NY 10065 USA. [Larsen, Dana M.] Mbed Pathol, Toronto, ON M5J 2H2, Canada. [Ueda, Takeshi] Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Dis Model, Hiroshima 7348553, Japan. [Straley, Kimberly; Yen, Katharine E.] Agios Pharmaceut, Cambridge, MA 02139 USA. [Melino, Gerry] MRC, Toxicol Unit, Leicester LE1 9HN, Leics, England. [Melino, Gerry] Univ Roma Tor Vergata, Dept Expt Med & Surg, I-00133 Rome, Italy. [Cimmino, Luisa; Aifantis, Iannis] NYU, Sch Med, Dept Pathol, Howard Hughes Med Inst, New York, NY 10016 USA. [Nolan, Garry P.] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Baxter Lab Stem Cell Biol, Stanford, CA 94305 USA. RP Mak, TW (reprint author), Univ Hlth Network, Campbell Family Inst Breast Canc Res, Toronto, ON M5G 2C1, Canada.; Mak, TW (reprint author), Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 1L7, Canada.; Mak, TW (reprint author), Univ Hlth Network, Ontario Canc Inst, Toronto, ON M5G 1L7, Canada.; Mak, TW (reprint author), Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada. EM tmak@uhnres.utoronto.ca FU Canadian Institutes of Health Research; Leukemia and Lymphoma Society FX We are grateful to Drs. John E. Dick (Princess Margaret Cancer Centre), Atsushi Hirao (University of Kanazawa), and all members of the Mak laboratory for their advice. We also appreciate the assistance of Ms. Irene Ng and the staff members of the flow cytometer facility, genotyping facility, and animal resource centre of the Princess Margaret Cancer Centre. Finally, we are grateful to Dr. Mary Saunders for scientific editing of the manuscript. This work was supported by grants to Drs. T.W.M. and R.A.C. from the Canadian Institutes of Health Research and the Leukemia and Lymphoma Society. K.E.Y. is an employee of and has an ownership interest in Agios Pharmaceuticals. NR 49 TC 5 Z9 5 U1 9 U2 14 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 AUG 8 PY 2016 VL 30 IS 2 BP 337 EP 348 DI 10.1016/j.ccell.2016.05.018 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DT2AC UT WOS:000381282200015 PM 27424808 ER PT J AU Sandulache, VC Hobbs, BP Mohamed, ASR Frank, SJ Song, J Ding, Y Ger, R Court, LE Kalpathy-Cramer, J Hazle, JD Wang, JH Awan, MJ Rosenthal, DI Garden, AS Gunn, GB Colen, RR Elshafeey, N Elbanan, M Hutcheson, KA Lewin, JS Chambers, MS Hofstede, TM Weber, RS Lai, SY Fuller, CD AF Sandulache, Vlad C. Hobbs, Brian P. Mohamed, Abdallah S. R. Frank, Steven J. Song, Juhee Ding, Yao Ger, Rachel Court, Laurence E. Kalpathy-Cramer, Jayashree Hazle, John D. Wang, Jihong Awan, Musaddiq J. Rosenthal, David I. Garden, Adam S. Gunn, G. Brandon Colen, Rivka R. Elshafeey, Nabil Elbanan, Mohamed Hutcheson, Katherine A. Lewin, Jan S. Chambers, Mark S. Hofstede, Theresa M. Weber, Randal S. Lai, Stephen Y. Fuller, Clifton D. CA Joint Head Neck Radiotherapy-MRI D TI Dynamic contrast-enhanced MRI detects acute radiotherapy-induced alterations in mandibular microvasculature: prospective assessment of imaging biomarkers of normal tissue injury SO SCIENTIFIC REPORTS LA English DT Article ID OROPHARYNGEAL CANCER; RADIATION-THERAPY; NECK-CANCER; OSTEORADIONECROSIS; PERFUSION; HEAD; MANAGEMENT; CARCINOMA; DIAGNOSIS; OUTCOMES AB Normal tissue toxicity is an important consideration in the continued development of more effective external beam radiotherapy (EBRT) regimens for head and neck tumors. The ability to detect EBRT-induced changes in mandibular bone vascularity represents a crucial step in decreasing potential toxicity. To date, no imaging modality has been shown to detect changes in bone vascularity in real time during treatment. Based on our institutional experience with multi-parametric MRI, we hypothesized that DCE-MRI can provide in-treatment information regarding EBRT-induced changes in mandibular vascularity. Thirty-two patients undergoing EBRT treatment for head and neck cancer were prospectively imaged prior to, mid-course, and following treatment. DCE-MRI scans were co-registered to dosimetric maps to correlate EBRT dose and change in mandibular bone vascularity as measured by K-trans and V-e. DCE-MRI was able to detect dose-dependent changes in both K-trans and V-e in a subset of patients. One patient who developed ORN during the study period demonstrated decreases in K-trans and V-e following treatment completion. We demonstrate, in a prospective imaging trial, that DCE-MRI can detect dose-dependent alterations in mandibular bone vascularity during chemoradiotherapy, providing biomarkers that are physiological correlates of acute of acute mandibular vascular injury and recovery temporal kinetics. C1 [Sandulache, Vlad C.; Hutcheson, Katherine A.; Lewin, Jan S.; Chambers, Mark S.; Hofstede, Theresa M.; Weber, Randal S.; Lai, Stephen Y.] UT MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX USA. [Hobbs, Brian P.; Song, Juhee] UT MD Anderson Canc Ctr, Dept Biostat, Houston, TX USA. [Mohamed, Abdallah S. R.; Frank, Steven J.; Rosenthal, David I.; Garden, Adam S.; Gunn, G. Brandon; Fuller, Clifton D.] UT MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX USA. [Ding, Yao; Hazle, John D.; Wang, Jihong] UT MD Anderson Canc Ctr, Dept Imaging Phys, Houston, TX USA. [Court, Laurence E.] UT MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX USA. [Kalpathy-Cramer, Jayashree] MIT, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Div Hlth Sci & Technol, Charlestown, MA USA. [Awan, Musaddiq J.] Case Western Reserve Univ, Dept Radiat Oncol, Cleveland, OH 44106 USA. [Colen, Rivka R.; Elshafeey, Nabil; Elbanan, Mohamed] UT MD Anderson Canc Ctr, Dept Diagnost Radiol, Houston, TX USA. [Lai, Stephen Y.] UT MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX USA. [Mohamed, Abdallah S. R.] Univ Alexandria, Fac Med, Dept Clin Oncol & Nucl Med, Alexandria, Egypt. RP Lai, SY (reprint author), UT MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX USA.; Fuller, CD (reprint author), UT MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX USA.; Lai, SY (reprint author), UT MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX USA. EM sylai@mdanderson.org; CDFuller@mdanderson.org OI Fuller, Clifton/0000-0002-5264-3994; Mohamed, Abdallah/0000-0003-2064-7613 FU SWOG Hope Foundation; National Institutes of Health Paul Calabresi Clinical Oncology Award Program [K12 CA088084]; Clinician Scientist Loan Repayment Program [L30 CA136381-02]; Elekta AB/MD Anderson Consortium; GE Medical Systems/MD Anderson Center for Advanced Biomedical Imaging In-Kind Award; MD Anderson Center for Radiation Oncology Research; MD Anderson Institutional Research Grant Program Award; National Cancer Institute [R21 CA178450, R03 CA188162]; MD Anderson Institutional Research Grant Program; NIH/NCI Cancer Center Support Grant [P30 CA016672]; National Institute for Dental and Craniofacial Research [R56 DE025248, R01 DE025248] FX The authors would like to thank Petra van Houdt and Uulke van de Heide, Department of Radiation Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands for assistance and conceptual development of image post-processing workflow; direct quality assurance, calculation, and image-post-processing of pharmacokinetic parameters. Dr. Fuller received/receives grant support from: the SWOG Hope Foundation Dr. Charles A. Coltman, Jr. Fellowship in Clinical Trials; the National Institutes of Health Paul Calabresi Clinical Oncology Award Program (K12 CA088084) and Clinician Scientist Loan Repayment Program (L30 CA136381-02); Elekta AB/MD Anderson Consortium; GE Medical Systems/MD Anderson Center for Advanced Biomedical Imaging In-Kind Award; the MD Anderson Center for Radiation Oncology Research, and an MD Anderson Institutional Research Grant Program Award. Dr. Lai receives grant support from Institutional Start-up Funds and the National Cancer Institute (R21 CA178450). Dr. Hutcheson receives grant support from the MD Anderson Institutional Research Grant Program and the National Cancer Institute (R03 CA188162). Dr. Hobbs was partially supported by NIH/NCI Cancer Center Support Grant (P30 CA016672). National Institute for Dental and Craniofacial Research (R56 DE025248 and R01 DE025248) provided support for the cooperative group to perform the included work. The listed funders/supporters played no role in the study design, collection, analysis, interpretation of data, manuscript writing, or decision to submit the report for publication. NR 34 TC 0 Z9 0 U1 0 U2 2 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 AUG 8 PY 2016 VL 6 AR 29864 DI 10.1038/srep29864 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DT0YZ UT WOS:000381210200001 ER PT J AU Toghyani, M Gillam, JE McNamara, AL Kuncic, Z AF Toghyani, M. Gillam, J. E. McNamara, A. L. Kuncic, Z. TI Polarisation-based coincidence event discrimination: an in silico study towards a feasible scheme for Compton-PET SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE Monte Carlo simulations; positron emission tomography; polarisation; Compton imaging ID ANGULAR-CORRELATION; PROTON-BEAMS; GAMMA-RAYS; ANNIHILATION; CAMERA; SCATTERING; SIMULATION; DESIGN AB Current positron emission tomography (PET) systems use temporally localised coincidence events discriminated by energy and time-of-flight information. The two annihilation photons are in an entangled polarisation state and, in principle, additional information from the polarisation correlation of photon pairs could be used to improve the accuracy of coincidence classification. In a previous study, we demonstrated that in principle, the polarisation correlation information could be transferred to an angular correlation in the distribution of scattered photon pairs in a planar Compton camera system. In the present study, we model a source-phantom-detector system using Geant4 and we develop a coincidence classification scheme that exploits the angular correlation of scattered annihilation quanta to improve the accuracy of coincidence detection. We find a 22% image quality improvement in terms of the peak signal-to-noise ratio when scattered coincidence events are discriminated solely by their angular correlation, thus demonstrating the feasibility of this novel classification scheme. By integrating scatter events (both single-single and single-only) with unscattered coincidence events discriminated using conventional methods, our results suggest that Compton-PET may be a promising candidate for optimal emission tomographic imaging. C1 [Toghyani, M.; Kuncic, Z.] Univ Sydney, Sch Phys, Sydney, NSW 2006, Australia. [Gillam, J. E.] Univ Sydney, Fac Hlth Sci, Brain & Mind Ctr, Camperdown, NSW 2050, Australia. [McNamara, A. L.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Kuncic, Z (reprint author), Univ Sydney, Sch Phys, Sydney, NSW 2006, Australia. EM zdenka.kuncic@sydney.edu.au RI McNamara, Aimee/C-9432-2009 OI McNamara, Aimee/0000-0001-8792-0464 NR 33 TC 0 Z9 0 U1 2 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD AUG 7 PY 2016 VL 61 IS 15 BP 5803 EP 5817 DI 10.1088/0031-9155/61/15/5803 PG 15 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA DX2NP UT WOS:000384207500020 PM 27405797 ER PT J AU Ferencik, M Hoffmann, U Bamberg, F Januzzi, JL AF Ferencik, Maros Hoffmann, Udo Bamberg, Fabian Januzzi, James L. TI Highly sensitive troponin and coronary computed tomography angiography in the evaluation of suspected acute coronary syndrome in the emergency department SO EUROPEAN HEART JOURNAL LA English DT Review DE Acute coronary syndrome; Acute chest pain; Highly sensitive troponin; Coronary computed tomography angiography ID ACUTE CHEST-PAIN; FRACTIONAL FLOW RESERVE; LEFT-VENTRICULAR FUNCTION; ACUTE MYOCARDIAL-INFARCTION; ACCELERATED DIAGNOSTIC PROTOCOL; 3RD UNIVERSAL DEFINITION; ROMICAT-II TRIAL; DUAL-SOURCE CT; CARDIAC TROPONIN; INTRAVASCULAR ULTRASOUND AB The evaluation of patients presenting to the emergency department with suspected acute coronary syndrome (ACS) remains a clinical challenge. The traditional assessment includes clinical risk assessment based on cardiovascular risk factors with serial electrocardiograms and cardiac troponin measurements, often followed by advanced cardiac testing as inpatient or outpatient (i. e. stress testing, imaging). Despite this costly and lengthy work-up, there is a non-negligible rate of missed ACS with an increased risk of death. There is a clinical need for diagnostic strategies that will lead to rapid and reliable triage of patients with suspected ACS. We provide an overview of the evidence for the role of highly sensitive troponin (hsTn) in the rapid and efficient evaluation of suspected ACS. Results of recent research studies have led to the introduction of hsTn with rapid rule-in and rule-out protocols into the guidelines. Highly sensitive troponin increases the sensitivity for the detection of myocardial infarction and decreases time to diagnosis; however, it may decrease the specificity, especially when used as a dichotomous variable, rather than continuous variable as recommended by guidelines; this may increase clinician uncertainty. We summarize the evidence for the use of coronary computed tomography angiography (CTA) as the rapid diagnostic tool in this population when used with conventional troponin assays. Coronary CTA significantly decreases time to diagnosis and discharge in patients with suspected ACS, while being safe. However, it may lead to increase in invasive procedures and includes radiation exposure. Finally, we outline the opportunities for the combined use of hsTn and coronary CTA that may result in increased efficiency, decreased need for imaging, lower cost, and decreased radiation dose. C1 [Ferencik, Maros] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, 3180 SW Sam Jackson Pk Rd,Mail Code UHN62, Portland, OR 97239 USA. [Ferencik, Maros; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Ferencik, Maros; Hoffmann, Udo; Januzzi, James L.] Harvard Med Sch, Boston, MA 02115 USA. [Ferencik, Maros; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Hoffmann, Udo; Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Bamberg, Fabian] Univ Tubingen, Dept Radiol, Tubingen, Germany. RP Ferencik, M (reprint author), Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, 3180 SW Sam Jackson Pk Rd,Mail Code UHN62, Portland, OR 97239 USA.; Ferencik, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.; Ferencik, M (reprint author), Harvard Med Sch, Boston, MA 02115 USA.; Ferencik, M (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. EM ferencik@ohsu.edu FU American Heart Association [13FTF16450001]; NIH [U01HL092040, U01HL092022]; Siemens Medical Solutions; Heart Flow Inc.; Bayer Healthcare (Berlin, Germany); Siemens Healthcare (Forchheim, Germany); Siemens; Thermo Fisher; Singulex FX M.F.: research grant/significant: American Heart Association Fellow to Faculty Award 13FTF16450001. U.H.: research grant/significant: NIH U01HL092040, U01HL092022, Siemens Medical Solutions, and Heart Flow Inc.; consultant/advisory board/significant: Heart Flow. F.B.: unrestricted research grant: Bayer Healthcare (Berlin, Germany) and Siemens Healthcare (Forchheim, Germany); speakers bureau: Bayer Healthcare (Berlin, Germany) and Siemens Healthcare (Forchheim, Germany). J.L.J.: research grant/significant: Siemens, Thermo Fisher, and Singulex; consultant/advisory board/significant: Critical Diagnostics, Sphingotec, and Roche. NR 92 TC 3 Z9 3 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 7 PY 2016 VL 37 IS 30 BP 2397 EP + DI 10.1093/eurheartj/ehw005 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW4FW UT WOS:000383599100008 PM 26843275 ER PT J AU Chan, PYL Tang, SM Au, SCL Rong, SS Lau, HHW Ko, STC Ng, DSC Chen, LJ Yam, JCS AF Chan, Priscilla Y. L. Tang, Shu-Min Au, Sunny C. L. Rong, Shi-Song Lau, Henry H. W. Ko, Simon T. C. Ng, Danny S. C. Chen, Li Jia Yam, Jason C. S. TI Association of Gestational Hypertensive Disorders with Retinopathy of prematurity: A Systematic Review and Meta-analysis SO SCIENTIFIC REPORTS LA English DT Review ID LOW-BIRTH-WEIGHT; RISK-FACTORS; INTERNATIONAL CLASSIFICATION; PREECLAMPTIC MOTHERS; ANGIOGENIC FACTORS; NEONATAL OUTCOMES; INFANTS; EXPERIENCE; NORTH AB The role of gestational hypertensive disorders, which includes both pre-eclampsia and gestational hypertension, in the development of retinopathy of prematurity (ROP) has been controversial. Therefore, this systematic review and meta-analysis is to evaluate the association between gestational hypertensive disoders and ROP. Eligible studies published up to June 5, 2016 were identified from MEDLINE and EMBASE that evaluated the association between the two conditions. Totally 1142 published records were retrieved for screening, 925 of them eligible for detailed evaluation. Finally 19 studies involving 45281 infants with 5388 cases of ROP met our criteria for meta-analysis. Gestational hypertensive disorders were not associated with ROP (unadjusted OR: 0.89; P = 0.38; adjusted OR: 1.35; P = 0.18). Subgroup analyses also revealed no significant association between ROP with pre-eclampsia (unadjusted OR: 0.85; P = 0.29; adjusted OR: 1.29; P = 0.28) or with gestational hypertension (unadjusted OR: 1.10; P = 0.39; adjusted OR: 1.25; P = 0.60) separately. Sensitivity analysis indicated our results were robust. We concluded no significant association between gestational hypertensive disorders and ROP. More large scale well-conducted prospective cohorts on the topic are needed. C1 [Chan, Priscilla Y. L.; Tang, Shu-Min; Au, Sunny C. L.; Rong, Shi-Song; Lau, Henry H. W.; Ng, Danny S. C.; Chen, Li Jia; Yam, Jason C. S.] Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Hong Kong, Hong Kong, Peoples R China. [Ko, Simon T. C.] Tung Wah Eastern Hosp, Dept Ophthalmol, Hong Kong, Hong Kong, Peoples R China. [Rong, Shi-Song] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Yam, JCS (reprint author), Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Hong Kong, Hong Kong, Peoples R China. EM yamcheuksing@cuhk.edu.hk RI Yam, Jason/I-5682-2014; Chen, Li Jia/I-5078-2014 OI Yam, Jason/0000-0002-2156-1486; Chen, Li Jia/0000-0003-3500-5840 NR 40 TC 0 Z9 0 U1 1 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 AUG 5 PY 2016 VL 6 AR 30732 DI 10.1038/srep30732 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DS6HE UT WOS:000380882100001 PM 27491726 ER PT J AU Friesen, M Hudak, CS Warren, CR Xia, F Cowan, CA AF Friesen, Max Hudak, Carolyn S. Warren, Curtis R. Xia, Fang Cowan, Chad A. TI Adipocyte insulin receptor activity maintains adipose tissue mass and lifespan SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Insulin receptor; Adipocyte-specific knockout mouse; Glucose metabolism; Insulin resistance; Metabolic disease; Type 2 diabetes ID RESISTANCE; GLUCOSE; MICE AB Type 2 diabetes follows a well-defined progressive pathogenesis, beginning with insulin resistance in metabolic tissues such as the adipose. Intracellular signaling downstream of insulin receptor activation regulates critical metabolic functions of adipose tissue, including glucose uptake, lipogenesis, lipolysis and adipokine secretion. Previous studies have used the aP2 promoter to drive Cre recombinase expression in adipose tissue. Insulin receptor (IR) knockout mice created using this aP2-Cre strategy (FIRKO mice) were protected from obesity and glucose intolerance. Later studies demonstrated the promiscuity of the aP2 promoter, casting doubts upon the tissue specificity of aP2-Cre models. It is our goal to use the increased precision of the Adipoq promoter to investigate adipocyte-specific IR function. Towards this end we generated an adipocyte-specific IR knockout (AIRKO) mouse using an Adipoq-driven Cre recombinase. Here we report AIRKO mice are less insulin sensitive throughout life, and less glucose tolerant than wild-type (WT) littermates at the age of 16 weeks. In contrast to WT littermates, the insulin sensitivity of AIRKO mice is unaffected by age or dietary regimen. At any age, AIRKO mice are comparably insulin resistant to old or obese WT mice and have a significantly reduced lifespan. Similar results were obtained when these phenotypes were re-examined in FIRKO mice. We also found that the AIRKO mouse is protected from high-fat diet-induced weight gain, corresponding with a 90% reduction in tissue weight of major adipose depots compared to WT littermates. Adipose tissue mass reduction is accompanied by hepatomegaly and increased hepatic steatosis. These data indicate that adipocyte IR function is crucial to systemic energy metabolism and has profound effects on adiposity, hepatic homeostasis and lifespan. (C) 2016 Published by Elsevier Inc. C1 [Friesen, Max; Hudak, Carolyn S.; Warren, Curtis R.; Xia, Fang; Cowan, Chad A.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Friesen, Max] Leiden Univ, Med Ctr, Dept Anat & Embryol, NL-2300 RC Leiden, Netherlands. [Cowan, Chad A.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Cowan, Chad A.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Cowan, CA (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cowan Lab, Sherman Fairchild Bldg,Rm 101-23,7 Divin Ave, Cambridge, MA 02138 USA. EM maxfriesen@gmail.com; chadacowan@gmail.com FU NIH/NIDDDK [R01DK095384-01]; Harvard University; Harvard Stem Cell Institute FX This work was supported by NIH/NIDDDK R01DK095384-01, startup funds to CAC from Harvard University and funding from the Harvard Stem Cell Institute. NR 17 TC 0 Z9 0 U1 11 U2 12 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 AUG 5 PY 2016 VL 476 IS 4 BP 487 EP 492 DI 10.1016/j.bbrc.2016.05.151 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA DR4QE UT WOS:000379886500048 PM 27246738 ER PT J AU Urso, K Alvarez, D Cremasco, V Tsang, K Grauel, A Lafyatis, R von Andrian, UH Ermann, J Aliprantis, AO AF Urso, Katia Alvarez, David Cremasco, Viviana Tsang, Kelly Grauel, Angelo Lafyatis, Robert von Andrian, Ulrich H. Ermann, Joerg Aliprantis, Antonios O. TI IL4RA on lymphatic endothelial cells promotes T cell egress during sclerodermatous graft versus host disease SO JCI INSIGHT LA English DT Article ID SYSTEMIC-SCLEROSIS; LYMPHOCYTE EGRESS; SPHINGOSINE 1-PHOSPHATE; SPHINGOSINE-1-PHOSPHATE; FIBROSIS; CANCER; BLOOD; MECHANISMS; EXPRESSION; SKIN AB Systemic sclerosis (SSc) is a potentially fatal autoimmune disorder with limited therapeutic options. Sclerodermatous graft versus host disease (sclGvHD), induced by transfer of B10. D2 splenocytes into BALB/c Rag2(-/-) mice, models an inflammatory subset of SSc characterized by a prominent IL13-induced gene expression signature in the skin. Host mice deficient in IL4RA, a subunit of the type II IL4/IL13 receptor, are protected from sclGvHD. While IL4RA has a well-established role in Th2 differentiation and alternative macrophage activation, we report here a previously unappreciated function for IL4RA in lymphatic endothelial cells (LECs): regulation of activated T cell egress. Seven days after splenocyte transfer, Il4ra(-/-) hosts had increased numbers of activated graft CD4(+) T cells in skin draining lymph nodes (dLNs) but fewer T cells in efferent lymph, blood, and skin. Sphingosine-1 phosphate (S1P), master regulator of lymphocyte egress from LNs, was lower in dLNs of Il4ra(-/-) hosts with a corresponding decrease of S1P kinase 1 (Sphk1) expression in LECs. Bypassing the efferent lymphatics via i. v. injection of CD4(+) T cells from dLNs of Il4ra(-/-) sclGvHD mice restored clinical GvHD in secondary Il4ra(-/-) recipients. These results identify a role for IL4RA and suggest that modulation of lymphocyte egress from LNs may be effective in SSc and GvHD. C1 [Urso, Katia; Tsang, Kelly; Ermann, Joerg; Aliprantis, Antonios O.] Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, 75 Francis St, Boston, MA 02115 USA. [Urso, Katia; Tsang, Kelly; Ermann, Joerg; Aliprantis, Antonios O.] Harvard Med Sch, Boston, MA USA. [Alvarez, David; von Andrian, Ulrich H.] Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA USA. [Cremasco, Viviana; Grauel, Angelo] Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA. [Lafyatis, Robert] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [von Andrian, Ulrich H.] Ragon Inst Massachusetts Gen Hosp MGH MIT & Harva, Cambridge, MA USA. RP Aliprantis, AO (reprint author), Merck Res Labs, 33 Ave Louis Pasteur, Boston, MA 02115 USA. EM antonios.aliprantis@gmail.com NR 46 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 2379-3708 J9 JCI INSIGHT JI JCI Insight PD AUG 4 PY 2016 VL 1 IS 12 AR e88057 DI 10.1172/jci.insight.88057 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA EB1NH UT WOS:000387118800007 ER PT J AU Fuchsberger, C Flannick, J Teslovich, TM Mahajan, A Agarwala, V Gaulton, KJ Ma, C Fontanillas, P Moutsianas, L McCarthy, DJ Rivas, MA Perry, JRB Sim, X Blackwell, TW Robertson, NR Rayner, NW Cingolani, P Locke, AE Tajes, JF Highland, HM Dupuis, J Chines, PS Lindgren, CM Hartl, C Jackson, AU Chen, H Huyghe, JR van de Bunt, M Pearson, RD Kumar, A Muller-Nurasyid, M Grarup, N Stringham, HM Gamazon, ER Lee, J Chen, YH Scott, RA Below, JE Chen, P Huang, J Go, MJ Stitzel, ML Pasko, D Parker, SCJ Varga, TV Green, T Beer, NL Day-Williams, AG Ferreira, T Fingerlin, T Horikoshi, M Hu, C Huh, I Ikram, MK Kim, BJ Kim, Y Kim, YJ Kwon, MS Lee, J Lee, S Lin, KH Maxwell, TJ Nagai, Y Wang, X Welch, RP Yoon, J Zhang, W Barzilai, N Voight, BF Han, BG Jenkinson, CP Kuulasmaa, T Kuusisto, J Manning, A Ng, MCY Palmer, ND Balkau, B Stancakova, A Abboud, HE Boeing, H Giedraitis, V Prabhakaran, D Gottesman, O Scott, J Carey, J Kwan, P Grant, G Smith, JD Neale, BM Purcell, S Butterworth, AS Howson, JMM Lee, HM Lu, YC Kwak, SH Zhao, W Danesh, J Lam, VKL Park, KS Saleheen, D So, WY Tam, CHT Afzal, U Aguilar, D Arya, R Aung, T Chan, E Navarro, C Cheng, CY Palli, D Correa, A Curran, JE Rybin, D Farook, VS Fowler, SP Freedman, BI Griswold, M Hale, DE Hicks, PJ Khor, CC Kumar, S Lehne, B Thuillier, D Lim, WY Liu, J van der Schouw, YT Loh, M Musani, SK Puppala, S Scott, WR Yengo, L Tan, ST Taylor, HA Thameem, F Wilson, G Wong, TY Njolstad, PR Levy, JC Mangino, M Bonnycastle, LL Schwarzmayr, T Fadista, J Surdulescu, GL Herder, C Groves, CJ Wieland, T Bork-Jensen, J Brandslund, I Christensen, C Koistinen, HA Doney, ASF Kinnunen, L Esko, T Farmer, AJ Hakaste, L Hodgkiss, D Kravic, J Lyssenko, V Hollensted, M Jorgensen, ME Jorgensen, T Ladenvall, C Justesen, JM Karajamaki, A Kriebel, J Rathmann, W Lannfelt, L Lauritzen, T Narisu, N Linneberg, A Melander, O Milani, L Neville, M Orho-Melander, M Qi, L Qi, QB Roden, M Rolandsson, O Swift, A Rosengren, AH Stirrups, K Wood, AR Mihailov, E Blancher, C Carneiro, MO Maguire, J Poplin, R Shakir, K Fennell, T DePristo, M de Angelis, MH Deloukas, P Gjesing, AP Jun, G Nilsson, P Murphy, J Onofrio, R Thorand, B Hansen, T Meisinger, C Hu, FB Isomaa, B Karpe, F Liang, LM Peters, A Huth, C O'Rahilly, SP Palmer, CNA Pedersen, O Rauramaa, R Tuomilehto, J Salomaa, V Watanabe, RM Syvanen, AC Bergman, RN Bharadwaj, D Bottinger, EP Cho, YS Chandak, GR Chan, JCN Chia, KS Daly, MJ Ebrahim, SB Langenberg, C Elliott, P Jablonski, KA Lehman, DM Jia, WP Ma, RCW Pollin, TI Sandhu, M Tandon, N Froguel, P Barroso, I Teo, YY Zeggini, E Loos, RJF Small, KS Ried, JS DeFronzo, RA Grallert, H Glaser, B Metspalu, A Wareham, NJ Walker, M Banks, E Gieger, C Ingelsson, E Im, HK Illig, T Franks, PW Buck, G Trakalo, J Buck, D Prokopenko, I Magi, R Lind, L Farjoun, Y Owen, KR Gloyn, AL Strauch, K Tuomi, T Kooner, JS Lee, JY Park, T Donnelly, P Morris, AD Hattersley, AT Bowden, DW Collins, FS Atzmon, G Chambers, JC Spector, TD Laakso, M Strom, TM Bell, GI Blangero, J Duggirala, R Tai, ES McVean, G Hanis, CL Wilson, JG Seielstad, M Frayling, TM Meigs, JB Cox, NJ Sladek, R Lander, ES Gabriel, S Burtt, NP Mohlke, KL Meitinger, T Groop, L Abecasis, G Florez, JC Scott, LJ Morris, AP Kang, HM Boehnke, M Altshuler, D McCarthy, MI AF Fuchsberger, Christian Flannick, Jason Teslovich, Tanya M. Mahajan, Anubha Agarwala, Vineeta Gaulton, Kyle J. Ma, Clement Fontanillas, Pierre Moutsianas, Loukas McCarthy, Davis J. Rivas, Manuel A. Perry, John R. B. Sim, Xueling Blackwell, Thomas W. Robertson, Neil R. Rayner, N. William Cingolani, Pablo Locke, Adam E. Tajes, Juan Fernandez Highland, Heather M. Dupuis, Josee Chines, Peter S. Lindgren, Cecilia M. Hartl, Christopher Jackson, Anne U. Chen, Han Huyghe, Jeroen R. van de Bunt, Martijn Pearson, Richard D. Kumar, Ashish Mueller-Nurasyid, Martina Grarup, Niels Stringham, Heather M. Gamazon, Eric R. Lee, Jaehoon Chen, Yuhui Scott, Robert A. Below, Jennifer E. Chen, Peng Huang, Jinyan Go, Min Jin Stitzel, Michael L. Pasko, Dorota Parker, Stephen C. J. Varga, Tibor V. Green, Todd Beer, Nicola L. Day-Williams, Aaron G. Ferreira, Teresa Fingerlin, Tasha Horikoshi, Momoko Hu, Cheng Huh, Iksoo Ikram, Mohammad Kamran Kim, Bong-Jo Kim, Yongkang Kim, Young Jin Kwon, Min-Seok Lee, Juyoung Lee, Selyeong Lin, Keng-Han Maxwell, Taylor J. Nagai, Yoshihiko Wang, Xu Welch, Ryan P. Yoon, Joon Zhang, Weihua Barzilai, Nir Voight, Benjamin F. Han, Bok-Ghee Jenkinson, Christopher P. Kuulasmaa, Teemu Kuusisto, Johanna Manning, Alisa Ng, Maggie C. Y. Palmer, Nicholette D. Balkau, Beverley Stancakova, Alena Abboud, Hanna E. Boeing, Heiner Giedraitis, Vilmantas Prabhakaran, Dorairaj Gottesman, Omri Scott, James Carey, Jason Kwan, Phoenix Grant, George Smith, Joshua D. Neale, Benjamin M. Purcell, Shaun Butterworth, Adam S. Howson, Joanna M. M. Lee, Heung Man Lu, Yingchang Kwak, Soo-Heon Zhao, Wei Danesh, John Lam, Vincent K. L. Park, Kyong Soo Saleheen, Danish So, Wing Yee Tam, Claudia H. T. Afzal, Uzma Aguilar, David Arya, Rector Aung, Tin Chan, Edmund Navarro, Carmen Cheng, Ching-Yu Palli, Domenico Correa, Adolfo Curran, Joanne E. Rybin, Denis Farook, Vidya S. Fowler, Sharon P. Freedman, Barry I. Griswold, Michael Hale, Daniel Esten Hicks, Pamela J. Khor, Chiea-Chuen Kumar, Satish Lehne, Benjamin Thuillier, Dorothee Lim, Wei Yen Liu, Jianjun van der Schouw, Yvonne T. Loh, Marie Musani, Solomon K. Puppala, Sobha Scott, William R. Yengo, Loic Tan, Sian-Tsung Taylor, Herman A., Jr. Thameem, Farook Wilson, Gregory, Sr. Wong, Tien Yin Njolstad, Pal Rasmus Levy, Jonathan C. Mangino, Massimo Bonnycastle, Lori L. Schwarzmayr, Thomas Fadista, Joao Surdulescu, Gabriela L. Herder, Christian Groves, Christopher J. Wieland, Thomas Bork-Jensen, Jette Brandslund, Ivan Christensen, Cramer Koistinen, Heikki A. Doney, Alex S. F. Kinnunen, Leena Esko, Tonu Farmer, Andrew J. Hakaste, Liisa Hodgkiss, Dylan Kravic, Jasmina Lyssenko, Valeriya Hollensted, Mette Jorgensen, Marit E. Jorgensen, Torben Ladenvall, Claes Justesen, Johanne Marie Karajamaki, Annemari Kriebel, Jennifer Rathmann, Wolfgang Lannfelt, Lars Lauritzen, Torsten Narisu, Narisu Linneberg, Allan Melander, Olle Milani, Lili Neville, Matt Orho-Melander, Marju Qi, Lu Qi, Qibin Roden, Michael Rolandsson, Olov Swift, Amy Rosengren, Anders H. Stirrups, Kathleen Wood, Andrew R. Mihailov, Evelin Blancher, Christine Carneiro, Mauricio O. Maguire, Jared Poplin, Ryan Shakir, Khalid Fennell, Timothy DePristo, Mark de Angelis, Martin Hrabe Deloukas, Panos Gjesing, Anette P. Jun, Goo Nilsson, Peter Murphy, Jacquelyn Onofrio, Robert Thorand, Barbara Hansen, Torben Meisinger, Christa Hu, Frank B. Isomaa, Bo Karpe, Fredrik Liang, Liming Peters, Annette Huth, Cornelia O'Rahilly, Stephen P. Palmer, Colin N. A. Pedersen, Oluf Rauramaa, Rainer Tuomilehto, Jaakko Salomaa, Veikko Watanabe, Richard M. Syvanen, Ann-Christine Bergman, Richard N. Bharadwaj, Dwaipayan Bottinger, Erwin P. Cho, Yoon Shin Chandak, Giriraj R. Chan, Juliana C. N. Chia, Kee Seng Daly, Mark J. Ebrahim, Shah B. Langenberg, Claudia Elliott, Paul Jablonski, Kathleen A. Lehman, Donna M. Jia, Weiping Ma, Ronald C. W. Pollin, Toni I. Sandhu, Manjinder Tandon, Nikhil Froguel, Philippe Barroso, Ines Teo, Yik Ying Zeggini, Eleftheria Loos, Ruth J. F. Small, Kerrin S. Ried, Janina S. DeFronzo, Ralph A. Grallert, Harald Glaser, Benjamin Metspalu, Andres Wareham, Nicholas J. Walker, Mark Banks, Eric Gieger, Christian Ingelsson, Erik Im, Hae Kyung Illig, Thomas Franks, Paul W. Buck, Gemma Trakalo, Joseph Buck, David Prokopenko, Inga Magi, Reedik Lind, Lars Farjoun, Yossi Owen, Katharine R. Gloyn, Anna L. Strauch, Konstantin Tuomi, Tiinamaija Kooner, Jaspal Singh Lee, Jong-Young Park, Taesung Donnelly, Peter Morris, Andrew D. Hattersley, Andrew T. Bowden, Donald W. Collins, Francis S. Atzmon, Gil Chambers, John C. Spector, Timothy D. Laakso, Markku Strom, Tim M. Bell, Graeme I. Blangero, John Duggirala, Ravindranath Tai, E. Shyong McVean, Gilean Hanis, Craig L. Wilson, James G. Seielstad, Mark Frayling, Timothy M. Meigs, James B. Cox, Nancy J. Sladek, Rob Lander, Eric S. Gabriel, Stacey Burtt, Noel P. Mohlke, Karen L. Meitinger, Thomas Groop, Leif Abecasis, Goncalo Florez, Jose C. Scott, Laura J. Morris, Andrew P. Kang, Hyun Min Boehnke, Michael Altshuler, David McCarthy, Mark I. TI The genetic architecture of type 2 diabetes SO NATURE LA English DT Article ID GENOME-WIDE ASSOCIATION; PROTEIN INTERACTION NETWORKS; SUSCEPTIBILITY LOCI; LOW-FREQUENCY; SEQUENCING ASSOCIATION; COMPLEX TRAITS; RARE VARIANTS; HUMAN-DISEASE; RISK; HERITABILITY AB The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes. C1 [Fuchsberger, Christian; Teslovich, Tanya M.; Ma, Clement; Sim, Xueling; Blackwell, Thomas W.; Locke, Adam E.; Jackson, Anne U.; Huyghe, Jeroen R.; Stringham, Heather M.; Lin, Keng-Han; Welch, Ryan P.; Kwan, Phoenix; Jun, Goo; Abecasis, Goncalo; Scott, Laura J.; Kang, Hyun Min; Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Fuchsberger, Christian] Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria. [Fuchsberger, Christian] Univ Lubeck, European Acad Bolzano Bozen EURAC, Ctr Biomed, Bolzano, Italy. [Flannick, Jason; Agarwala, Vineeta; Fontanillas, Pierre; Lindgren, Cecilia M.; Hartl, Christopher; Green, Todd; Manning, Alisa; Carey, Jason; Grant, George; Neale, Benjamin M.; Purcell, Shaun; Esko, Tonu; Carneiro, Mauricio O.; Maguire, Jared; Poplin, Ryan; Shakir, Khalid; Fennell, Timothy; DePristo, Mark; Murphy, Jacquelyn; Onofrio, Robert; Banks, Eric; Gabriel, Stacey; Burtt, Noel P.; Florez, Jose C.; Altshuler, David] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Flannick, Jason; Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Mahajan, Anubha; Gaulton, Kyle J.; Moutsianas, Loukas; McCarthy, Davis J.; Rivas, Manuel A.; Perry, John R. B.; Robertson, Neil R.; Rayner, N. William; Tajes, Juan Fernandez; Lindgren, Cecilia M.; van de Bunt, Martijn; Pearson, Richard D.; Kumar, Ashish; Chen, Yuhui; Ferreira, Teresa; Horikoshi, Momoko; Ingelsson, Erik; Prokopenko, Inga; Gloyn, Anna L.; Donnelly, Peter; McVean, Gilean; Morris, Andrew P.; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England. [Agarwala, Vineeta] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [McCarthy, Davis J.; Donnelly, Peter] Univ Oxford, Dept Stat, Oxford, England. [Perry, John R. B.; Pasko, Dorota; Wood, Andrew R.; Frayling, Timothy M.] Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England. [Perry, John R. B.; Scott, Robert A.; Langenberg, Claudia; Wareham, Nicholas J.] Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England. [Perry, John R. 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Shyong] Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore. [Navarro, Carmen] IMIB Arrixaca, Murcia Reg Hlth Council, Dept Epidemiol, Murcia, Spain. [Navarro, Carmen] Univ Murcia, CIBERESP, Murcia, Spain. [Navarro, Carmen] Univ Murcia, Sch Med, Unit Prevent Med & Publ Hlth, E-30001 Murcia, Spain. [Palli, Domenico] Canc Res & Prevent Inst ISPO, Florence, Italy. [Correa, Adolfo; Taylor, Herman A., Jr.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. [Curran, Joanne E.; Kumar, Satish; Blangero, John] Univ Texas Rio Grande Valley, Reg Acad Hlth Ctr, South Texas Diabet & Obes Inst, Brownsville, TX USA. [Farook, Vidya S.; Puppala, Sobha; Duggirala, Ravindranath] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Freedman, Barry I.] Wake Forest Sch Med, Nephrol Sect, Dept Internal Med, Winston Salem, NC USA. [Griswold, Michael] Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, Jackson, MS 39216 USA. [Khor, Chiea-Chuen] Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Paediat, Singapore, Singapore. [Khor, Chiea-Chuen; Liu, Jianjun] ASTAR, Genome Inst Singapore, Div Human Genet, Singapore, Singapore. [Thuillier, Dorothee; Yengo, Loic; Froguel, Philippe] Univ Lille, Lille Pasteur Inst, CNRS UMR8199, Lille, France. [van der Schouw, Yvonne T.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Loh, Marie] Univ Oulu, Inst Hlth Sci, Oulu, Finland. [Loh, Marie] ASTAR, TLGM, Singapore, Singapore. [Musani, Solomon K.] Univ Mississippi, Med Ctr, Jackson Heart Study, Jackson, MS 39216 USA. [Wilson, Gregory, Sr.] Jackson State Univ, Coll Publ Serv, Jackson, MS USA. [Njolstad, Pal Rasmus] Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, Bergen, Norway. [Njolstad, Pal Rasmus] Haukeland Hosp, Dept Pediat, Bergen, Norway. [Schwarzmayr, Thomas; Wieland, Thomas; Strom, Tim M.; Meitinger, Thomas] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, Neuherberg, Germany. [Fadista, Joao; Kravic, Jasmina; Lyssenko, Valeriya; Ladenvall, Claes; Rosengren, Anders H.; Groop, Leif] Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden. [Herder, Christian; Roden, Michael] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany. [Herder, Christian; Kriebel, Jennifer; Roden, Michael; de Angelis, Martin Hrabe; Thorand, Barbara; Meisinger, Christa; Peters, Annette; Huth, Cornelia; Grallert, Harald] German Ctr Diabet Res DZD, Neuherberg, Germany. [Brandslund, Ivan] Univ Southern Denmark, Inst Reg Hlth Res, Odense, Denmark. [Brandslund, Ivan] Vejle Hosp, Dept Clin Biochem, Vejle, Denmark. [Christensen, Cramer] Vejle Hosp, Dept Internal Med & Endocrinol, Vejle, Denmark. [Koistinen, Heikki A.; Kinnunen, Leena; Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland. [Koistinen, Heikki A.; Hakaste, Liisa; Tuomi, Tiinamaija] Univ Helsinki, Abdominal Ctr Endocrinol, Helsinki, Finland. [Koistinen, Heikki A.; Hakaste, Liisa; Tuomi, Tiinamaija] Univ Helsinki, Cent Hosp, Helsinki, Finland. [Koistinen, Heikki A.] Minerva Fdn, Helsinki, Finland. [Koistinen, Heikki A.] Univ Helsinki, Dept Med, Helsinki, Finland. [Doney, Alex S. F.] Ninewells Hosp & Med Sch, Med Res Inst, Div Cardiovasc & Diabet Med, Dundee, Scotland. [Esko, Tonu; Milani, Lili; Mihailov, Evelin; Metspalu, Andres; Magi, Reedik; Morris, Andrew P.] Univ Tartu, Estonian Genome Ctr, Tartu, Estonia. [Esko, Tonu; Altshuler, David] Harvard Med Sch, Dept Genet, Boston, MA USA. [Esko, Tonu] Boston Childrens Hosp, Div Endocrinol, Boston, MA USA. [Farmer, Andrew J.] Univ Oxford, Nuffield Dept Primary Care Hlth Sci, Oxford, England. [Hakaste, Liisa; Isomaa, Bo; Tuomi, Tiinamaija] Folkhalsan Res Ctr, Helsinki, Finland. [Hakaste, Liisa; Tuomi, Tiinamaija] Univ Helsinki, Res Programs Unit, Diabet & Obes, Helsinki, Finland. [Jorgensen, Marit E.] Steno Diabet Ctr, Gentofte, Denmark. [Jorgensen, Torben; Linneberg, Allan] Capital Reg Denmark, Res Ctr Prevent & Hlth, Glostrup, Denmark. [Jorgensen, Torben] Univ Copenhagen, Inst Hlth Sci, Dept Publ Hlth, Copenhagen, Denmark. [Jorgensen, Torben] Aalborg Univ, Med, Aalborg, Denmark. [Karajamaki, Annemari] Vaasa Cent Hosp, Dept Primary Hlth Care, Vaasa, Finland. [Karajamaki, Annemari] Vaasa Hlth Care Ctr, Ctr Diabet, Vaasa, Finland. [Kriebel, Jennifer; Thorand, Barbara; Meisinger, Christa; Peters, Annette; Huth, Cornelia; Grallert, Harald; Gieger, Christian] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany. [Kriebel, Jennifer; Grallert, Harald; Gieger, Christian; Illig, Thomas] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany. [Rathmann, Wolfgang] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Biometr & Epidemiol, Dusseldorf, Germany. [Lauritzen, Torsten] Aarhus Univ, Sect Gen Practice, Dept Publ Hlth, Aarhus, Denmark. [Linneberg, Allan] Rigshosp, Dept Clin Expt Res, Glostrup, Denmark. [Linneberg, Allan] Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark. [Melander, Olle] Lund Univ, Dept Clin Sci Hypertens & Cardiovasc, Malmo, Sweden. [Neville, Matt; Karpe, Fredrik; Owen, Katharine R.; Gloyn, Anna L.; McCarthy, Mark I.] Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England. [Orho-Melander, Marju] Lund Univ, Dept Clin Sci Diabet & Cardiovasc Dis, Genet Epidemiol, Malmo, Sweden. [Qi, Lu; Qi, Qibin; Hu, Frank B.; Franks, Paul W.] Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Qi, Lu] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Qi, Lu] Harvard Med Sch, Boston, MA USA. [Qi, Qibin] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA. [Roden, Michael] Univ Dusseldorf, Fac Med, Dept Endocrinol & Diabetol, Dusseldorf, Germany. [Rolandsson, Olov; Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Blancher, Christine; Buck, Gemma; Trakalo, Joseph; Buck, David] Univ Oxford, Nuffield Dept Med, Oxford Genom Ctr, High Throughput Genom,Wellcome Trust Ctr Human Ge, Oxford, England. [de Angelis, Martin Hrabe] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Expt Genet, Neuherberg, Germany. [de Angelis, Martin Hrabe] Tech Univ Munich, Ctr Life & Food Sci Weihenstephan, Freising Weihenstephan, Germany. [Deloukas, Panos] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England. [Deloukas, Panos] King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah, Saudi Arabia. [Nilsson, Peter] Lund Univ, Dept Clin Sci, Med, Malmo, Sweden. [Hansen, Torben] Univ Southern Denmark, Fac Hlth Sci, Odense, Denmark. [Isomaa, Bo] Dept Social Serv & Hlth Care, Pietarsaari, Finland. [O'Rahilly, Stephen P.; Barroso, Ines] Univ Cambridge, Inst Metab Sci, Metab Res Labs, Cambridge, England. [Palmer, Colin N. A.] Univ Dundee, Ninewells Hosp & Med Sch, Pat Macpherson Ctr Pharmacogenet & Pharmacogen, Dundee, Scotland. [Rauramaa, Rainer] Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio, Finland. [Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria. [Tuomilehto, Jaakko] King Abdulaziz Univ, Diabet Res Grp, Jeddah, Saudi Arabia. [Tuomilehto, Jaakko] Autonomous Univ Madrid, Univ Hosp LaPaz, Inst Invest Sanitaria Hosp Univ LaPaz IdiPAZ, Madrid, Spain. [Tuomilehto, Jaakko; Salomaa, Veikko] Natl Inst Hlth & Welf, Helsinki, Finland. [Watanabe, Richard M.] Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. [Watanabe, Richard M.] Univ Southern Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA USA. [Watanabe, Richard M.] Univ Southern Calif, Keck Sch Med, Dabet & Obes Res Inst, Los Angeles, CA USA. [Syvanen, Ann-Christine] Uppsala Univ, Mol Med & Sci Life Lab, Dept Med Sci, Uppsala, Sweden. [Bergman, Richard N.] Cedars Sinai Diabet & Obes Res Inst, Los Angeles, CA USA. [Bharadwaj, Dwaipayan] CSIR IGIB, Funct Genom Unit, New Delhi, India. [Cho, Yoon Shin] Hallym Univ, Dept Biomed Sci, Chunchon, South Korea. [Chandak, Giriraj R.] CSIR Ctr Cellular & Mol Biol, Hyderabad, Telangana, India. [Chan, Juliana C. N.; Ma, Ronald C. W.] Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China. [Chan, Juliana C. N.; Ma, Ronald C. W.] Chinese Univ Hong Kong, Hong Kong Inst Diabet & Obes, Hong Kong, Hong Kong, Peoples R China. [Elliott, Paul] Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England. [Jablonski, Kathleen A.] George Washington Univ, Biostat Ctr, Rockville, MD USA. [Pollin, Toni I.] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Pollin, Toni I.] Univ Maryland, Sch Med, Program Personalized & Genom Med, Baltimore, MD 21201 USA. [Tandon, Nikhil] All India Inst Med Sci, Dept Endocrinol & Metab, New Delhi, India. [Froguel, Philippe; Prokopenko, Inga] Imperial Coll London, Sch Publ Hlth, Dept Genom Common Dis, London, England. [Teo, Yik Ying] Natl Univ Singapore, Inst Life Sci, Singapore, Singapore. [Teo, Yik Ying] Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore, Singapore. [Glaser, Benjamin] Hadassah Hebrew Univ Med Ctr, Endocrinol & Metab Serv, Jerusalem, Israel. [Walker, Mark] Newcastle Univ, Inst Cellular Med, Sch Med, Newcastle Upon Tyne, Tyne & Wear, England. [Ingelsson, Erik] Uppsala Univ, Mol Epidemiol & Sci Life Lab, Dept Med Sci, Uppsala, Sweden. [Illig, Thomas] Hannover Med Sch, Hannover Unified Biobank, Hannover, NH, Germany. [Illig, Thomas] Hannover Med Sch, Inst Human Genet, Hannover, NH, Germany. [Lind, Lars] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Farjoun, Yossi] Broad Inst, Data Sci & Data Engn, Cambridge, MA USA. [Tuomi, Tiinamaija; Groop, Leif] Univ Helsinki, FIMM, Helsinki, Finland. [Kooner, Jaspal Singh; Chambers, John C.] Imperial Coll London, Imperial Coll Healthcare NHS Trust, London, England. [Morris, Andrew D.] Ninewells Hosp & Med Sch, Ctr Mol Med, Clin Res Ctr, Dundee, Scotland. [Morris, Andrew D.] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland. [Hattersley, Andrew T.] Univ Exeter, Sch Med, Exeter, Devon, England. [Atzmon, Gil] Univ Haifa, Dept Nat Sci, Haifa, Israel. [Strom, Tim M.; Meitinger, Thomas] Tech Univ Munich, Inst Human Genet, Munich, Germany. [Bell, Graeme I.] Univ Chicago, Dept Med Genet, Chicago, IL 60637 USA. [Bell, Graeme I.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Tai, E. Shyong] Duke NUS Med Sch Singapore, Cardiovasc & Metab Disorders Program, Singapore, Singapore. [McVean, Gilean] Univ Oxford, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford, England. [Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA. [Seielstad, Mark] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. [Seielstad, Mark] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Seielstad, Mark] Blood Syst Res Inst, San Francisco, CA USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.] Harvard Med Sch, Dept Med, Boston, MA USA. [Sladek, Rob] McGill Univ, Dept Med, Div Endocrinol & Metab, Montreal, PQ, Canada. [Lander, Eric S.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Florez, Jose C.; Altshuler, David] Harvard Med Sch, Dept Med, Boston, MA USA. [Florez, Jose C.; Altshuler, David] Massachusetts Gen Hosp, Dept Med, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA. [Morris, Andrew P.] Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England. [Altshuler, David] MIT, Dept Biol, Cambridge, MA USA. RP Boehnke, M (reprint author), Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.; McCarthy, MI (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.; McCarthy, MI (reprint author), Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England. EM boehnke@umich.edu; mark.mccarthy@drl.ox.ac.uk RI Hrabe de Angelis, Martin/F-5531-2012; Jun, Goo/F-1941-2017; Kinnunen, Leena/B-7059-2012; van der Schouw, Yvonne/F-8327-2014; Ma, Ronald/C-2788-2009; Yengo, Loic/D-2692-2017; Palmer, Colin/C-7053-2008; Chan, Juliana /B-7918-2016; Peters, Annette/A-6117-2011; Park, Kyong Soo/C-2265-2008; Justesen, Johanne Marie/L-6023-2015; Deloukas, Panos/B-2922-2013; Hu, Cheng/C-3346-2008; Grallert, Harald/B-3424-2013; Grarup, Niels/K-2807-2015 OI Varga, Tibor/0000-0002-2383-699X; Tai, E Shyong/0000-0003-2929-8966; Hattersley, Andrew/0000-0001-5620-473X; Linneberg, Allan/0000-0002-0994-0184; Hrabe de Angelis, Martin/0000-0002-7898-2353; Jun, Goo/0000-0003-0891-0204; Gieger, Christian/0000-0001-6986-9554; Kinnunen, Leena/0000-0001-8739-4812; mangino, massimo/0000-0002-2167-7470; Koistinen, Heikki/0000-0001-7870-070X; Meisinger, Christa/0000-0002-9026-6544; Chen, Han/0000-0002-9510-4923; Tuomi, Tiinamaija/0000-0002-8306-6202; Small, Kerrin/0000-0003-4566-0005; Khor, Chiea Chuen/0000-0002-1128-4729; van der Schouw, Yvonne/0000-0002-4605-435X; Ma, Ronald/0000-0002-1227-803X; Yengo, Loic/0000-0002-4272-9305; Palmer, Colin/0000-0002-6415-6560; Chan, Juliana /0000-0003-1325-1194; Park, Kyong Soo/0000-0003-3597-342X; Justesen, Johanne Marie/0000-0002-0484-8522; Deloukas, Panos/0000-0001-9251-070X; Grarup, Niels/0000-0001-5526-1070 FU British Heart Foundation [RG/14/5/30893, SP/04/002, SP/09/002]; CIHR; Medical Research Council [G0601261, G0601966, G0700931, G0800270, G0900747-‐91070, MC_UU_12012/5, MC_UU_12015/1, MR/K002414/1, MR/L01341X/1]; NCI NIH HHS [K12CA139160]; NHGRI NIH HHS [U01 HG005773, U01HG005773, U54 HG003067, U54HG003067]; NHLBI NIH HHS [HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C, R01 HL102830, R01HL102830]; NIA NIH HHS [1R01AG042188, P01 AG027734, P01AG027734, P30 AG038072, P30AG038072, R01 AG042188, R01 AG046949, R01AG046949]; NIDDK NIH HHS [R01DK066358, 1RC2DK088389, DK072193, DK085501, DK085524, DK085526, DK085545, DK085584, DK088389, DK093757, DK098032, K24 DK080140, K24DK080140, P30 DK020595, P30DK020595, P60 DK020595, P60DK20595, R00 DK092251, R00 DK099240, R00DK092251, R01 DK066358, R01 DK072193, R01 DK073541, R01 DK093757, R01 DK098032, R01 DK101478, R01 DK106236, R01DK062370, R01DK073541, R01DK098032, RC2 DK088389, RC2-‐DK088389, RC2DK088389, U01 DK062370, U01 DK078616, U01 DK085501, U01 DK085524, U01 DK085526, U01 DK085545, U01 DK085584, U01DK085501, U01DK085526]; NIGMS NIH HHS [T32 GM007753, T32GM007753]; NIMH NIH HHS [R01 MH090937, R01 MH101820, R01MH090937, R01MH101820]; NIMHD NIH HHS [U54 MD007588]; PHS HHS [HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C]; Wellcome Trust [064890, 083948, 084723, 085475, 086596, 090367, 090532, 092447, 095101, 095552, 098017, 098051, 098381, 100956] NR 68 TC 34 Z9 34 U1 38 U2 39 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 AUG 4 PY 2016 VL 536 IS 7614 BP 41 EP + DI 10.1038/nature18642 PG 29 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DS7YM UT WOS:000380999200026 PM 27398621 ER PT J AU Lee, ASY Kranzusch, PJ Doudna, JA Cate, JHD AF Lee, Amy S. Y. Kranzusch, Philip J. Doudna, Jennifer A. Cate, Jamie H. D. TI eIF3d is an mRNA cap-binding protein that is required for specialized translation initiation SO NATURE LA English DT Article ID DEPENDENT TRANSLATION; C-JUN; MECHANISM; MODEL; MTOR; PHOSPHORYLATION; ACTIVATION; COMPLEXES; LINKING; QUALITY AB Eukaryotic mRNAs contain a 5' cap structure that is crucial for recruitment of the translation machinery and initiation of protein synthesis. mRNA recognition is thought to require direct interactions between eukaryotic initiation factor 4E (eIF4E) and the mRNA cap. However, translation of numerous capped mRNAs remains robust during cellular stress, early development, and cell cycle progression(1) despite inactivation of eIF4E. Here we describe a cap-dependent pathway of translation initiation in human cells that relies on a previously unknown cap-binding activity of eIF3d, a subunit of the 800-kilodalton eIF3 complex. A 1.4 angstrom crystal structure of the eIF3d cap-binding domain reveals unexpected homology to endonucleases involved in RNA turnover, and allows modelling of cap recognition by eIF3d. eIF3d makes specific contacts with the cap, as exemplified by cap analogue competition, and these interactions are essential for assembly of translation initiation complexes on eIF3-specialized mRNAs(2) such as the cell proliferation regulator c-Jun (also known as JUN). The c-Jun mRNA further encodes an inhibitory RNA element that blocks eIF4E recruitment, thus enforcing alternative cap recognition by eIF3d. Our results reveal a mechanism of cap-dependent translation that is independent of eIF4E, and illustrate how modular RNA elements work together to direct specialized forms of translation initiation. C1 [Lee, Amy S. Y.; Kranzusch, Philip J.; Doudna, Jennifer A.; Cate, Jamie H. D.] Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA. [Lee, Amy S. Y.; Kranzusch, Philip J.; Doudna, Jennifer A.; Cate, Jamie H. D.] Univ Calif Berkeley, Ctr RNA Syst Biol, Berkeley, CA 94720 USA. [Kranzusch, Philip J.; Doudna, Jennifer A.] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA. [Doudna, Jennifer A.; Cate, Jamie H. D.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA. [Doudna, Jennifer A.; Cate, Jamie H. D.] Lawrence Berkeley Natl Lab, Phys Biosci Div, Berkeley, CA 94720 USA. [Doudna, Jennifer A.] Univ Calif Berkeley, Innovat Genom Initiat, Berkeley, CA 94720 USA. [Lee, Amy S. Y.] Brandeis Univ, Dept Biol, Waltham, MA 02454 USA. [Kranzusch, Philip J.] Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA. [Kranzusch, Philip J.] Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. RP Cate, JHD (reprint author), Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA.; Cate, JHD (reprint author), Univ Calif Berkeley, Ctr RNA Syst Biol, Berkeley, CA 94720 USA.; Cate, JHD (reprint author), Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.; Cate, JHD (reprint author), Lawrence Berkeley Natl Lab, Phys Biosci Div, Berkeley, CA 94720 USA. EM jcate@lbl.gov FU UC Office of the President, Multicampus Research Programs and Initiatives grant [MR-15-328599]; Program for Breakthrough Biomedical Research; Sandler Foundation; NIH [S10RR025622]; NIGMS Center for RNA Systems Biology [P50-GM201706] FX The authors thank J. Berger and K. Chat for discussions. X-ray data were collected at Beamline 8.3.1 of the Lawrence Berkeley National Laboratory Advanced Light Source (ALS), supported in part by the UC Office of the President, Multicampus Research Programs and Initiatives grant MR-15-328599 and the Program for Breakthrough Biomedical Research, which is partially funded by the Sandler Foundation. The authors are grateful to J. Holton, G. Meigs (ALS), and T. Doukov (SSRL) for help with S-SAD data collection. This work used the Vincent J. Proteomics/Mass Spectrometry Laboratory at UC Berkeley, supported in part by NIH S10 Instrumentation Grant S10RR025622. This work was funded by the NIGMS Center for RNA Systems Biology (P50-GM201706). J.A.D. is an HHMI Investigator. A.S.Y.L. is supported as an American Cancer Society Postdoctoral Fellow (PF-14-108-01-RMC) and P.J.K. is supported as an HHMI Fellow of the Life Sciences Research Foundation. NR 34 TC 6 Z9 6 U1 6 U2 6 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 AUG 4 PY 2016 VL 536 IS 7614 BP 96 EP + DI 10.1038/nature18954 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DS7YM UT WOS:000380999200037 PM 27462815 ER PT J AU Shaw, MA Kombrinck, KW McElhinney, KE Sweet, DR Flick, MJ Palumbo, JS Cheng, M Esmon, NL Esmon, CT Brill, A Wagner, DD Degen, JL Mullins, ES AF Shaw, Maureen A. Kombrinck, Keith W. McElhinney, Kathryn E. Sweet, David R. Flick, Matthew J. Palumbo, Joseph S. Cheng, Mei Esmon, Naomi L. Esmon, Charles T. Brill, Alexander Wagner, Denisa D. Degen, Jay L. Mullins, Eric S. TI Limiting prothrombin activation to meizothrombin is compatible with survival but significantly alters hemostasis in mice SO BLOOD LA English DT Article ID THROMBIN MUTANT W215A/E217A; FUNCTIONAL-CHARACTERIZATION; TISSUE FACTOR; TUMOR-CELLS; MOUSE MODEL; FACTOR-XIII; FACTOR-V; INTERMEDIATE; DEFICIENCY; ANTICOAGULANT AB Thrombin-mediated proteolysis is central to hemostatic function but also plays a prominent role in multiple disease processes. The proteolytic conversion of fII to alpha-thrombin (fIIa) by the prothrombinase complex occurs through 2 parallel pathways: (1) the inactive intermediate, prethrombin; or (2) the proteolytically active intermediate, meizothrombin (fIIa(MZ)). FIIa(MZ) has distinct catalytic properties relative to fIIa, including diminished fibrinogen cleavage and increased protein C activation. Thus, fII activation may differentially influence hemostasis and disease depending on the pathway of activation. To determine the in vivo physiologic and pathologic consequences of restricting thrombin generation to fIIa(MZ), mutations were introduced into the endogenous fII gene, resulting in expression of prothrombin carrying 3 amino acid substitutions (R157A, R268A, and K281A) to limit activation events to yield only fIIa(MZ). Homozygous fII(MZ) mice are viable, express fII levels comparable with fII(WT) mice, and have reproductive success. Although in vitro studies revealed delayed generation of fIIa(MZ) enzyme activity, platelet aggregation by fII(MZ) is similar to fII(WT). Consistent with prior analyses of human fIIa(MZ), significant prolongation of clotting times was observed for fII(MZ) plasma. Adult fII(MZ) animals displayed significantly compromised hemostasis in tail bleeding assays, but did not demonstrate overt bleeding. More notably, fII(MZ) mice had 2 significant phenotypic advantages over fII(WT) animals: protection from occlusive thrombosis after arterial injury and markedly diminished metastatic potential in a setting of experimental tumor metastasis to the lung. Thus, these novel animals will provide a valuable tool to assess the role of both fIIa and fIIa(MZ) in vivo. C1 [Shaw, Maureen A.; McElhinney, Kathryn E.; Sweet, David R.; Palumbo, Joseph S.; Mullins, Eric S.] Cincinnati Childrens Res Fdn, Div Hematol, Canc & Blood Dis Inst, MLC 7015,3333 Burnet Ave, Cincinnati, OH 45229 USA. [Kombrinck, Keith W.; Flick, Matthew J.; Degen, Jay L.] Cincinnati Childrens Res Fdn, Div Expt Hematol & Canc Biol, Cincinnati, OH USA. [Cheng, Mei; Esmon, Naomi L.; Esmon, Charles T.] Oklahoma Med Res Fdn, Coagulat Biol Lab, 825 NE 13th St, Oklahoma City, OK 73104 USA. [Brill, Alexander] Univ Birmingham, Coll Med & Dent Sci, Inst Cardiovasc Sci, Birmingham, W Midlands, England. [Brill, Alexander; Wagner, Denisa D.] Harvard Med Sch, Program Cellular & Mol Med, Boston Childrens Hosp, Boston, MA USA. [Brill, Alexander; Wagner, Denisa D.] Harvard Med Sch, Div Hematol Oncol, Boston Childrens Hosp, Boston, MA USA. RP Mullins, ES (reprint author), Cincinnati Childrens Res Fdn, Div Hematol, Canc & Blood Dis Inst, MLC 7015,3333 Burnet Ave, Cincinnati, OH 45229 USA. EM eric.mullins@cchmc.org FU National Institutes of Health, National Heart, Lung and Blood Institute [K08HL105672, R01HL102101] FX This study was supported by National Institutes of Health, National Heart, Lung and Blood Institute grants K08HL105672 (E.S.M.) and R01HL102101 (D.D.W.). NR 47 TC 1 Z9 1 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 AUG 4 PY 2016 VL 128 IS 5 BP 721 EP 731 DI 10.1182/blood-2015-11-680280 PG 11 WC Hematology SC Hematology GA DW7PI UT WOS:000383843000016 PM 27252233 ER PT J AU Henssen, AG Jiang, E Zhuang, JL Pinello, L Socci, ND Koche, R Gonen, M Villasante, CM Armstrong, SA Bauer, DE Weng, ZP Kentsis, A AF Henssen, Anton G. Jiang, Eileen Zhuang, Jiali Pinello, Luca Socci, Nicholas D. Koche, Richard Gonen, Mithat Villasante, Camila M. Armstrong, Scott A. Bauer, Daniel E. Weng, Zhiping Kentsis, Alex TI Forward genetic screen of human transposase genomic rearrangements SO BMC GENOMICS LA English DT Article ID HAMSTER OVARY CELLS; T-LYMPHOCYTES; HPRT GENE; DESIGN; ART; LOCUS; TELOMERASE; MUTATIONS; DELETION AB Background: Numerous human genes encode potentially active DNA transposases or recombinases, but our understanding of their functions remains limited due to shortage of methods to profile their activities on endogenous genomic substrates. Results: To enable functional analysis of human transposase-derived genes, we combined forward chemical genetic hypoxanthine-guanine phosphoribosyltransferase 1 (HPRT1) screening with massively parallel paired-end DNA sequencing and structural variant genome assembly and analysis. Here, we report the HPRT1 mutational spectrum induced by the human transposase PGBD5, including PGBD5-specific signal sequences (PSS) that serve as potential genomic rearrangement substrates. Conclusions: The discovered PSS motifs and high-throughput forward chemical genomic screening approach should prove useful for the elucidation of endogenous genome remodeling activities of PGBD5 and other domesticated human DNA transposases and recombinases. C1 [Henssen, Anton G.; Jiang, Eileen; Villasante, Camila M.; Kentsis, Alex] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Mol Pharmacol Program, 1275 York Ave, New York, NY 10021 USA. [Zhuang, Jiali; Weng, Zhiping] Univ Massachusetts, Sch Med, Program Bioinformat & Integrat Biol, Dept Biochem & Mol Pharmacol, Worcester, MA USA. [Pinello, Luca; Bauer, Daniel E.] Dana Farber Canc Inst, Boston, MA USA. [Pinello, Luca; Bauer, Daniel E.] Boston Childrens Hosp, Boston, MA USA. [Socci, Nicholas D.] Mem Sloan Kettering Canc Ctr, Bioinformat Core, New York, NY USA. [Koche, Richard; Armstrong, Scott A.] Sloan Kettering Inst, Canc Biol & Genet Program, New York, NY USA. [Gonen, Mithat] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY USA. [Armstrong, Scott A.; Kentsis, Alex] Mem Sloan Kettering Canc Ctr, Dept Pediat, 1275 York Ave, New York, NY 10021 USA. [Kentsis, Alex] Cornell Univ, Weill Cornell Med Coll, New York, NY 10021 USA. RP Kentsis, A (reprint author), Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Mol Pharmacol Program, 1275 York Ave, New York, NY 10021 USA.; Kentsis, A (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pediat, 1275 York Ave, New York, NY 10021 USA.; Kentsis, A (reprint author), Cornell Univ, Weill Cornell Med Coll, New York, NY 10021 USA. EM kentsisresearchgroup@gmail.com FU University of Essen Pediatric Oncology Research Program; NIH [K08 DK093705, K08 CA160660]; Burroughs Wellcome Fund; Josie Robertson Investigator Program; Sarcoma Foundation of America; NHGRI Career Development Award [K99 HG008399] FX This work was supported by the University of Essen Pediatric Oncology Research Program (A.H.), NIH K08 DK093705 (D.E.B.), NIH K08 CA160660, Burroughs Wellcome Fund, Josie Robertson Investigator Program, and the Sarcoma Foundation of America (A.K.). L.P. is supported by NHGRI Career Development Award K99 HG008399. We thank the MSKCC Integrated Genomics Core Facility and Bioinformatics Core Facility for assistance with DNA sequencing and analysis (NIH P30 CA008748). NR 28 TC 1 Z9 1 U1 2 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD AUG 4 PY 2016 VL 17 AR 548 DI 10.1186/s12864-016-2877-x PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA DT1EW UT WOS:000381225500002 PM 27491780 ER PT J AU Polfus, LM Khajuria, RK Schick, UM Pankratz, N Pazoki, R Brody, JA Chen, MH Auer, PL Floyd, JS Huang, J Lange, L van Rooij, FJA Gibbs, RA Metcalf, G Muzny, D Veeraraghavan, N Walter, K Chen, L Yanek, L Becker, LC Peloso, GM Wakabayashi, A Kals, M Metspalu, A Esko, T Fox, K Wallace, R Franceschini, N Matijevic, N Rice, KM Bartz, TM Lyytikainen, LP Kahonen, M Lehtimaki, T Raitakari, OT Li-Gao, R Mook-Kanamori, DO Lettre, G van Duijn, CM Franco, OH Rich, SS Rivadeneira, F Hofman, A Uitterlinden, AG Wilson, JG Psaty, BM Soranzo, N Dehghan, A Boerwinkle, E Zhang, XL Johnson, AD O'Donnell, CJ Johnsen, JM Reiner, AP Ganesh, SK Sankaran, VG AF Polfus, Linda M. Khajuria, Rajiv K. Schick, Ursula M. Pankratz, Nathan Pazoki, Raha Brody, Jennifer A. Chen, Ming-Huei Auer, Paul L. Floyd, James S. Huang, Jie Lange, Leslie van Rooij, Frank J. A. Gibbs, Richard A. Metcalf, Ginger Muzny, Donna Veeraraghavan, Narayanan Walter, Klaudia Chen, Lu Yanek, Lisa Becker, Lewis C. Peloso, Gina M. Wakabayashi, Aoi Kals, Mart Metspalu, Andres Esko, Tonu Fox, Keolu Wallace, Robert Franceschini, Nora Matijevic, Nena Rice, Kenneth M. Bartz, Traci M. Lyytikainen, Leo-Pekka Kahonen, Mika Lehtimaki, Terho Raitakari, Olli T. Li-Gao, Ruifang Mook-Kanamori, Dennis O. Lettre, Guillaume van Duijn, Cornelia M. Franco, Oscar H. Rich, Stephen S. Rivadeneira, Fernando Hofman, Albert Uitterlinden, Andre G. Wilson, James G. Psaty, Bruce M. Soranzo, Nicole Dehghan, Abbas Boerwinkle, Eric Zhang, Xiaoling Johnson, Andrew D. O'Donnell, Christopher J. Johnsen, Jill M. Reiner, Alexander P. Ganesh, Santhi K. Sankaran, Vijay G. TI Whole-Exome Sequencing Identifies Loci Associated with Blood Cell Traits and Reveals a Role for Alternative GFI1B Splice Variants in Human Hematopoiesis SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DIAMOND-BLACKFAN ANEMIA; GRAY PLATELET SYNDROME; HEMATOLOGICAL TRAITS; GENETIC-VARIATION; GFI-1B; DIFFERENTIATION; METAANALYSIS; CONSORTIUM; MUTATIONS; DISORDER AB Circulating blood cell counts and indices are important indicators of hematopoietic function and a number of clinical parameters, such as blood oxygen-carrying capacity, inflammation, and hemostasis. By performing whole-exome sequence association analyses of hematologic quantitative traits in 15,459 community-dwelling individuals, followed by in silico replication in up to 52,024 independent samples, we identified two previously undescribed coding variants associated with lower platelet count: a common missense variant in CPS1 (rs1047891, MAF=0.33, discovery + replication p=6.38 x 10(-10)) and a rare synonymous variant in GFI1B (rs150813342, MAF=0.009, discovery + replication p=1.79 x 10(-27)). By performing CRISPR/Cas9 genome editing in hematopoietic cell lines and follow-up targeted knockdown experiments in primary human hematopoietic stem and progenitor cells, we demonstrate an alternative splicing mechanism by which the GFI1B rs150813342 variant suppresses formation of a GFI1B isoform that preferentially promotes megakaryocyte differentiation and platelet production. These results demonstrate how unbiased studies of natural variation in blood cell traits can provide insight into the regulation of human hematopoiesis. C1 [Polfus, Linda M.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA. [Khajuria, Rajiv K.; Wakabayashi, Aoi; Sankaran, Vijay G.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Khajuria, Rajiv K.; Wakabayashi, Aoi; Sankaran, Vijay G.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Khajuria, Rajiv K.; Wakabayashi, Aoi; Sankaran, Vijay G.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Khajuria, Rajiv K.] Charite, Berlin Brandenburg Sch Regenerat Therapies, D-13353 Berlin, Germany. [Schick, Ursula M.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA. [Pankratz, Nathan] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55454 USA. [Pazoki, Raha; van Rooij, Frank J. A.; Franco, Oscar H.; Dehghan, Abbas] Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands. [Brody, Jennifer A.; Floyd, James S.; Rice, Kenneth M.; Bartz, Traci M.; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Brody, Jennifer A.; Floyd, James S.; Rice, Kenneth M.; Bartz, Traci M.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Chen, Ming-Huei] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Auer, Paul L.] Univ Wisconsin Milwaukee, Sch Publ Hlth, Milwaukee, WI 53205 USA. [Huang, Jie; Walter, Klaudia; Chen, Lu; Soranzo, Nicole] Wellcome Trust Sanger Inst, Human Genet, Hinxton CB10 1HH, England. [Lange, Leslie] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Gibbs, Richard A.; Metcalf, Ginger; Muzny, Donna; Veeraraghavan, Narayanan] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Chen, Lu; Soranzo, Nicole] Univ Cambridge, Dept Haematol, Cambridge CB2 0AH, England. [Yanek, Lisa; Becker, Lewis C.] Johns Hopkins Univ, Sch Med, Dept Med, GeneSTAR Res Program,Div Gen Internal Med, Baltimore, MD 21205 USA. [Peloso, Gina M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kals, Mart; Metspalu, Andres; Esko, Tonu] Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia. [Fox, Keolu] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Wallace, Robert] Univ Iowa, Coll Publ Hlth, Iowa City, IA 52242 USA. [Franceschini, Nora] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC 27599 USA. [Matijevic, Nena] Univ Texas Hlth Sci Ctr Houston, Dept Surg, Houston, TX 77030 USA. [Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland. [Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Univ Tampere, Sch Med, Tampere 33520, Finland. [Kahonen, Mika] Tampere Univ Hosp, Dept Clin Physiol, Tampere 33521, Finland. [Kahonen, Mika] Univ Tampere, Sch Med, Tampere 33521, Finland. [Raitakari, Olli T.] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku 20520, Finland. [Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku 20520, Finland. [Li-Gao, Ruifang; Mook-Kanamori, Dennis O.] Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2300 RA Leiden, Netherlands. [Mook-Kanamori, Dennis O.] King Faisal Specialist Hosp & Res Ctr, Dept Biostat, Epidemiol, Epidemiol Sect, Riyadh 11211, Saudi Arabia. [Mook-Kanamori, Dennis O.] King Faisal Specialist Hosp & Res Ctr, Dept Comp Sci, Riyadh 11211, Saudi Arabia. [Lettre, Guillaume] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Lettre, Guillaume] Univ Montreal, Montreal, PQ H1T 1C8, Canada. [van Duijn, Cornelia M.; Rivadeneira, Fernando; Hofman, Albert; Uitterlinden, Andre G.] Erasmus Univ, Med Ctr, Dept Internal Med, NL-3000 DR Rotterdam, Netherlands. [Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA. [Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98101 USA. [Zhang, Xiaoling] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Zhang, Xiaoling] Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA. [Zhang, Xiaoling] Boston Univ, Sch Publ Hlth, Dept Med, Boston, MA 02118 USA. [Zhang, Xiaoling] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Johnson, Andrew D.] NHLBI, Cardiovasc Epidemiol & Human Genom Branch, Framingham Heart Study, Framingham, MA 01702 USA. [O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Johnsen, Jill M.] Bloodworks Northwest, Seattle, WA 98102 USA. [Reiner, Alexander P.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Womens Hlth Initiat Clin Coordinating Ctr, Seattle, WA 98109 USA. [Ganesh, Santhi K.] Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. [Ganesh, Santhi K.] Univ Michigan, Dept Human Genet, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. RP Sankaran, VG (reprint author), Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.; Sankaran, VG (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.; Sankaran, VG (reprint author), Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. EM sankaran@broadinstitute.org RI Floyd, James/G-7563-2015; Johnson, Andrew/G-6520-2013 FU NIH [HL122684, DK103794, HL120791]; Wellcome Trust [WT098051, WT091310]; EU [257082, HEALTH-F5-2011-282510]; NIH Research (NIHR) Blood and Transplant Research Unit (BTRU) in Donor Health and Genomics at the University of Cambridge; NHS Blood and Transplant (NHSBT) FX The work described in this manuscript was supported in part by NIH grants HL122684 to S.K.G. and DK103794 and HL120791 to V.G.S. N.S. is supported by the Wellcome Trust (grant codes WT098051 and WT091310), the EU 7th Framework Programme (EPIGENESYS grant code 257082 and BLUEPRINT grant code HEALTH-F5-2011-282510) and the NIH Research (NIHR) Blood and Transplant Research Unit (BTRU) in Donor Health and Genomics at the University of Cambridge in partnership with NHS Blood and Transplant (NHSBT). NR 33 TC 5 Z9 5 U1 2 U2 3 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 AUG 4 PY 2016 VL 99 IS 2 BP 481 EP 488 DI 10.1016/j.ajhg.2016.06.016 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA DT6TO UT WOS:000381617200020 PM 27486782 ER PT J AU Kimball, AB Okun, MM Williams, DA Gottlieb, AB Papp, KA Zouboulis, CC Armstrong, AW Kerdel, F Gold, MH Forman, SB Korman, NJ Giamarellos-Bourboulis, EJ Crowley, JJ Lynde, C Reguiai, Z Prens, EP Alwawi, E Mostafa, NM Pinsky, B Sundaram, M Gu, YH Carlson, DM Jemec, GBE AF Kimball, Alexa B. Okun, Martin M. Williams, David A. Gottlieb, Alice B. Papp, Kim A. Zouboulis, Christos C. Armstrong, April W. Kerdel, Francisco Gold, Michael H. Forman, Seth B. Korman, Neil J. Giamarellos-Bourboulis, Evangelos J. Crowley, Jeffrey J. Lynde, Charles Reguiai, Ziad Prens, Errol-Prospero Alwawi, Eihab Mostafa, Nael M. Pinsky, Brett Sundaram, Murali Gu, Yihua Carlson, Dawn M. Jemec, Gregor B. E. TI Two Phase 3 Trials of Adalimumab for Hidradenitis Suppurativa SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MODERATE; PREVALENCE; PSORIASIS; THERAPY; INVERSA; DISEASE; ALPHA AB BACKGROUND Hidradenitis suppurativa is a painful, chronic inflammatory skin disease with few options for effective treatment. In a phase 2 trial, adalimumab, an antibody against tumor necrosis factor a, showed efficacy against hidradenitis suppurativa. METHODS PIONEER I and II were similarly designed, phase 3 multicenter trials of adalimumab for hidradenitis suppurativa, with two double-blind, placebo-controlled periods. In period 1, patients were randomly assigned in a 1: 1 ratio to 40 mg of adalimumab weekly or matching placebo for 12 weeks. In period 2, patients were reassigned to adalimumab at a weekly or every-other-week dose or to placebo for 24 weeks. The primary end point was a clinical response, defined as at least a 50% reduction from baseline in the abscess and inflammatory-nodule count, with no increase in abscess or draining-fistula counts, at week 12. RESULTS We enrolled 307 patients in PIONEER I and 326 in PIONEER II. Clinical response rates at week 12 were significantly higher for the groups receiving adalimumab weekly than for the placebo groups: 41.8% versus 26.0% in PIONEER I (P=0.003) and 58.9% versus 27.6% in PIONEER II (P<0.001). Patients receiving adalimumab had significantly greater improvement than the placebo groups in rank-ordered secondary outcomes (lesions, pain, and the modified Sartorius score for disease severity) at week 12 in PIONEER II only. Serious adverse events in period 1 (excluding worsening of underlying disease) occurred in 1.3% of patients receiving adalimumab and 1.3% of those receiving placebo in PIONEER I and in 1.8% and 3.7% of patients, respectively, in PIONEER II. In period 2, the rates of serious adverse events were 4.6% or less in all the groups in both studies, with no significant between-group differences. CONCLUSIONS Treatment with adalimumab (40 mg weekly), as compared with placebo, resulted in significantly higher clinical response rates in both trials at 12 weeks; rates of serious adverse events were similar in the study groups. C1 [Kimball, Alexa B.] Harvard Med Sch, Boston, MA USA. [Kimball, Alexa B.] Massachusetts Gen Hosp, Boston, MA USA. [Gottlieb, Alice B.] Tufts Med Ctr, Boston, MA USA. [Okun, Martin M.; Williams, David A.; Alwawi, Eihab; Mostafa, Nael M.; Pinsky, Brett; Sundaram, Murali; Gu, Yihua; Carlson, Dawn M.] AbbVie, N Chicago, IL USA. [Papp, Kim A.] Prob Med Res, Waterloo, ON, Canada. [Papp, Kim A.] K Papp Clin Res, Waterloo, ON, Canada. [Lynde, Charles] Lynde Ctr Dermatol, Markham, ON, Canada. [Lynde, Charles] Prob Med Res, Markham, ON, Canada. [Zouboulis, Christos C.] Dessau Med Ctr, Dept Dermatol, Dessau, Germany. [Zouboulis, Christos C.] Dessau Med Ctr, Dept Venereol, Dessau, Germany. [Zouboulis, Christos C.] Dessau Med Ctr, Dept Allergol, Dessau, Germany. [Zouboulis, Christos C.] Dessau Med Ctr, Dept Immunol, Dessau, Germany. [Armstrong, April W.] Univ So Calif, Los Angeles, CA USA. [Crowley, Jeffrey J.] Bakersfield Dermatol, Bakersfield, CA USA. [Kerdel, Francisco] Florida Acad Dermatol Ctr, Miami, FL USA. [Forman, Seth B.] Forward Clin Trials, Tampa, FL USA. [Gold, Michael H.] Tennessee Clin Res Ctr, Nashville, TN USA. [Korman, Neil J.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Giamarellos-Bourboulis, Evangelos J.] Univ Athens, Sch Med, Dept Internal Med 4, Athens, Greece. [Reguiai, Ziad] CHU Reims, Hop Robert Debre, Serv Dermatol, Reims, France. [Prens, Errol-Prospero] Erasmus Univ, Med Ctr, Rotterdam, Netherlands. [Jemec, Gregor B. E.] Univ Copenhagen, Roskilde Hosp, Dept Dermatol, Copenhagen, Denmark. [Jemec, Gregor B. E.] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark. RP Kimball, AB (reprint author), 375 Longwood Ave,3rd Fl, Boston, MA 02215 USA. EM harvardskinstudies@gmail.com OI Jemec, Gregor/0000-0002-0712-2540 FU AbbVie FX Funded by AbbVie; ClinicalTrials.gov numbers, NCT01468207 and NCT01468233 for PIONEER I and PIONEER II, respectively. NR 25 TC 8 Z9 8 U1 4 U2 5 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 AUG 4 PY 2016 VL 375 IS 5 BP 422 EP 434 DI 10.1056/NEJMoa1504370 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA DS7AN UT WOS:000380934900006 PM 27518661 ER PT J AU Pritchard, CC Mateo, J Walsh, MF De Sarkar, N Abida, W Beltran, H Garofalo, A Gulati, R Carreira, S Eeles, R Elemento, O Rubin, MA Robinson, D Lonigro, R Hussain, M Chinnaiyan, A Vinson, J Filipenko, J Garraway, L Taplin, ME AlDubayan, S Han, GC Beightol, M Morrissey, C Nghiem, B Cheng, HH Montgomery, B Walsh, T Casadei, S Berger, M Zhang, L Zehir, A Vijai, J Scher, HI Sawyers, C Schultz, N Kantoff, PW Solit, D Robson, M Van Allen, EM Offit, K de Bono, J Nelson, PS AF Pritchard, C. C. Mateo, J. Walsh, M. F. De Sarkar, N. Abida, W. Beltran, H. Garofalo, A. Gulati, R. Carreira, S. Eeles, R. Elemento, O. Rubin, M. A. Robinson, D. Lonigro, R. Hussain, M. Chinnaiyan, A. Vinson, J. Filipenko, J. Garraway, L. Taplin, M. -E. AlDubayan, S. Han, G. C. Beightol, M. Morrissey, C. Nghiem, B. Cheng, H. H. Montgomery, B. Walsh, T. Casadei, S. Berger, M. Zhang, L. Zehir, A. Vijai, J. Scher, H. I. Sawyers, C. Schultz, N. Kantoff, P. W. Solit, D. Robson, M. Van Allen, E. M. Offit, K. de Bono, J. Nelson, P. S. TI Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID OVARIAN-CANCER; BREAST-CANCER; RISK; DISEASE; BRCA1; AGGRESSIVENESS; ASSOCIATION; GUIDELINES; VARIANTS; GENOMICS AB BACKGROUND Inherited mutations in DNA-repair genes such as BRCA2 are associated with increased risks of lethal prostate cancer. Although the prevalence of germline mutations in DNA-repair genes among men with localized prostate cancer who are unselected for family predisposition is insufficient to warrant routine testing, the frequency of such mutations in patients with metastatic prostate cancer has not been established. METHODS We recruited 692 men with documented metastatic prostate cancer who were unselected for family history of cancer or age at diagnosis. We isolated germline DNA and used multiplex sequencing assays to assess mutations in 20 DNA-repair genes associated with autosomal dominant cancer-predisposition syndromes. RESULTS A total of 84 germline DNA-repair gene mutations that were presumed to be deleterious were identified in 82 men (11.8%); mutations were found in 16 genes, including BRCA2 (37 men [5.3%]), ATM (11 [1.6%]), CHEK2 (10 [1.9% of 534 men with data]), BRCA1 (6 [0.9%]), RAD51D (3 [0.4%]), and PALB2 (3 [0.4%]). Mutation frequencies did not differ according to whether a family history of prostate cancer was present or according to age at diagnosis. Overall, the frequency of germline mutations in DNA-repair genes among men with metastatic prostate cancer significantly exceeded the prevalence of 4.6% among 499 men with localized prostate cancer (P<0.001), including men with high-risk disease, and the prevalence of 2.7% in the Exome Aggregation Consortium, which includes 53,105 persons without a known cancer diagnosis (P<0.001). CONCLUSIONS In our multicenter study, the incidence of germline mutations in genes mediating DNA-repair processes among men with metastatic prostate cancer was 11.8%, which was significantly higher than the incidence among men with localized prostate cancer. The frequencies of germline mutations in DNA-repair genes among men with metastatic disease did not differ significantly according to age at diagnosis or family history of prostate cancer. C1 [Pritchard, C. C.; Beightol, M.; Morrissey, C.; Nghiem, B.; Cheng, H. H.; Montgomery, B.; Walsh, T.; Casadei, S.; Nelson, P. S.] Univ Washington, Seattle, WA 98195 USA. [De Sarkar, N.; Gulati, R.; Nelson, P. S.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Mateo, J.; Carreira, S.; Eeles, R.; de Bono, J.] Inst Canc Res, London, England. [Mateo, J.; Carreira, S.; Eeles, R.; de Bono, J.] Royal Marsden Hosp, London, England. [Walsh, M. F.; Abida, W.; Berger, M.; Zhang, L.; Zehir, A.; Vijai, J.; Scher, H. I.; Sawyers, C.; Schultz, N.; Kantoff, P. W.; Solit, D.; Robson, M.; Offit, K.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Beltran, H.; Elemento, O.; Rubin, M. A.] Weill Cornell Med Coll, New York, NY USA. [Vinson, J.; Filipenko, J.] Prostate Canc Clin Trials Consortium, New York, NY USA. [Robinson, D.; Lonigro, R.; Hussain, M.; Chinnaiyan, A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Chinnaiyan, A.; Sawyers, C.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Garofalo, A.; Garraway, L.; Taplin, M. -E.; AlDubayan, S.; Han, G. C.; Van Allen, E. M.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nelson, PS (reprint author), Fred Hutchinson Canc Res Ctr, Div Human Biol, 1100 Fairview Ave,Mailstop D4-100, Seattle, WA 98109 USA. EM pnelson@fhcrc.org OI Rubin, Mark/0000-0002-8321-9950 FU Stand Up To Cancer FX Funded by Stand Up To Cancer and others. NR 40 TC 28 Z9 30 U1 12 U2 20 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 AUG 4 PY 2016 VL 375 IS 5 BP 443 EP 453 DI 10.1056/NEJMoa1603144 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA DS7AN UT WOS:000380934900008 PM 27433846 ER PT J AU Sheridan, RL AF Sheridan, Robert L. TI Fire-Related Inhalation Injury SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID LOW-TIDAL-VOLUME; SMOKE-INHALATION; BURN PATIENTS; LUNG INJURY; SEVERITY; BRONCHOSCOPY; PNEUMONIA C1 [Sheridan, Robert L.] Shriners Hosp Children, Burn Serv, 51 Blossom St, Boston, MA 02114 USA. [Sheridan, Robert L.] Massachusetts Gen Hosp, Div Burns, Boston, MA 02114 USA. [Sheridan, Robert L.] Harvard Med Sch, Dept Surg, Boston, MA USA. RP Sheridan, RL (reprint author), Shriners Hosp Children, Burn Serv, 51 Blossom St, Boston, MA 02114 USA. EM rsheridan@mgh.harvard.edu NR 29 TC 2 Z9 2 U1 4 U2 8 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 AUG 4 PY 2016 VL 375 IS 5 BP 464 EP 469 DI 10.1056/NEJMra1601128 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA DS7AN UT WOS:000380934900010 PM 27518664 ER PT J AU Mou, HM Vinarsky, V Tata, PR Brazauskas, K Choi, SH Crooke, AK Zhang, B Solomon, GM Turner, B Bihler, H Harrington, J Lapey, A Channick, C Keyes, C Freund, A Artandi, S Mense, M Rowe, S Engelhardt, JF Hsu, YC Rajagopal, J AF Mou, Hongmei Vinarsky, Vladimir Tata, Purushothama Rao Brazauskas, Karissa Choi, Soon H. Crooke, Adrianne K. Zhang, Bing Solomon, George M. Turner, Brett Bihler, Hermann Harrington, Jan Lapey, Allen Channick, Colleen Keyes, Colleen Freund, Adam Artandi, Steven Mense, Martin Rowe, Steven Engelhardt, John F. Hsu, Ya-Chieh Rajagopal, Jayaraj TI Dual SMAD Signaling Inhibition Enables Long-Term Expansion of Diverse Epithelial Basal Cells SO CELL STEM CELL LA English DT Article ID HUMAN EPIDERMAL-KERATINOCYTES; HUMAN AIRWAY EPITHELIUM; STEM-CELLS; CYSTIC-FIBROSIS; TGF-BETA; GROWTH-FACTOR; SELF-RENEWAL; MAINTENANCE; NICHE; DIFFERENTIATION AB Functional modeling of many adult epithelia is limited by the difficulty in maintaining relevant stem cell populations in culture. Here, we show that dual inhibition of SMAD signaling pathways enables robust expansion of primary epithelial basal cell populations. We find that TGF beta/BMP/SMAD pathway signaling is strongly activated in luminal and suprabasal cells of several epithelia, but suppressed in p63+ basal cells. In airway epithelium, SMAD signaling promotes differentiation, and its inhibition leads to stem cell hyperplasia. Using dual SMAD signaling inhibition in a feeder-free culture system, we have been able to expand airway basal stemcells from multiple species. Expanded cells can produce functional airway epithelium physiologically responsive to clinically relevant drugs, such as CFTR modulators. This approach is effective for the clonal expansion of single human cells and for basal cell populations from epithelial tissues from all three germ layers and therefore may be broadly applicable for modeling of epithelia. C1 [Mou, Hongmei; Vinarsky, Vladimir; Tata, Purushothama Rao; Brazauskas, Karissa; Rajagopal, Jayaraj] Massachusetts Gen Hosp, Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02114 USA. [Mou, Hongmei; Vinarsky, Vladimir; Tata, Purushothama Rao; Rajagopal, Jayaraj] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Mou, Hongmei; Brazauskas, Karissa; Lapey, Allen; Rajagopal, Jayaraj] Massachusetts Gen Hosp Children, Div Pediat Pulm Med, Boston, MA 02114 USA. [Vinarsky, Vladimir; Channick, Colleen; Keyes, Colleen; Rajagopal, Jayaraj] Massachusetts Gen Hosp, Dept Internal Med, Div Pulm & Crit Care Med, Boston, MA 02114 USA. [Choi, Soon H.; Crooke, Adrianne K.; Engelhardt, John F.] Univ Iowa, Coll Med, Dept Anat & Cell Biol, Iowa City, IA 52242 USA. [Zhang, Bing; Hsu, Ya-Chieh] Harvard Univ, Dept Stem Cell & Regenerat Biol, 7 Divin Ave, Cambridge, MA 02138 USA. [Zhang, Bing; Hsu, Ya-Chieh] Harvard Stem Cell Inst, 7 Divin Ave, Cambridge, MA 02138 USA. [Solomon, George M.; Rowe, Steven] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35233 USA. [Turner, Brett; Rowe, Steven] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL 35233 USA. [Rowe, Steven] Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol, Birmingham, AL 35294 USA. [Solomon, George M.; Rowe, Steven] Univ Alabama Birmingham, Gregory Fleming James Cyst Fibrosis Res Ctr, Birmingham, AL 35233 USA. [Bihler, Hermann; Harrington, Jan; Mense, Martin] Cyst Fibrosis Fdn Therapeut, CFFT Lab, Lexington, MA 01730 USA. [Freund, Adam; Artandi, Steven] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Freund, Adam; Artandi, Steven] Stanford Univ, Dept Biochem, Stanford, CA 94305 USA. [Rajagopal, Jayaraj] Massachusetts Eye & Ear, Div Otol & Laryngol, Boston, MA 02114 USA. RP Rajagopal, J (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02114 USA.; Rajagopal, J (reprint author), Harvard Stem Cell Inst, Cambridge, MA 02138 USA.; Rajagopal, J (reprint author), Massachusetts Gen Hosp Children, Div Pediat Pulm Med, Boston, MA 02114 USA.; Rajagopal, J (reprint author), Massachusetts Gen Hosp, Dept Internal Med, Div Pulm & Crit Care Med, Boston, MA 02114 USA.; Rajagopal, J (reprint author), Massachusetts Eye & Ear, Div Otol & Laryngol, Boston, MA 02114 USA. EM jrajagopal@partners.org FU NIH [R01HL116756, R01HL118185, DK047967, HL051670, K08HL124298, T32HL087735, K99HL127181, R00 AR063127]; Cystic Fibrosis Foundation [RAJAGO12G0, RAJAGO12I0]; Smith Family Awards; March of Dimes Basil O'Connor Starter Scholar Awards FX J.R. is a New York Stem Cell Foundation Robertson Investigator and a Maroni Research Scholar at MGH. We thank Marina Mazur (the University of Alabama at Birmingham) for assistance with cell culture and the entire J.R. laboratory for constructive comments. This research was supported by grants from the NIH (R01HL116756 and R01HL118185 to J.R.; DK047967 and HL051670 to J.F.E; K08HL124298 to V.V.; T32HL087735 to H.M.; K99HL127181 to P.R.T.; R00 AR063127 to Y.-C.H.), the Cystic Fibrosis Foundation (RAJAGO12G0 and RAJAGO12I0 to J.R.), and the Smith Family Awards and March of Dimes Basil O'Connor Starter Scholar Awards (to Y.-C.H.). NR 38 TC 3 Z9 3 U1 3 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD AUG 4 PY 2016 VL 19 IS 2 BP 217 EP 231 DI 10.1016/j.stem.2016.05.012 PG 15 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA DT6VG UT WOS:000381622000015 PM 27320041 ER PT J AU Carreras-Torres, R Haycock, PC Relton, CL Martin, RM Smith, GD Kraft, P Gao, C Tworoger, S Le Marchand, L Wilkens, LR Park, SL Haiman, C Field, JK Davies, M Marcus, M Liu, G Caporaso, NE Christiani, DC Wei, YY Chen, C Doherty, JA Severi, G Goodman, GE Hung, RJ Amos, CI McKay, J Johansson, M Brennan, P AF Carreras-Torres, Robert Haycock, Philip C. Relton, Caroline L. Martin, Richard M. Smith, George Davey Kraft, Peter Gao, Chi Tworoger, Shelley Le Marchand, Loic Wilkens, Lynne R. Park, Sungshim L. Haiman, Christopher Field, John K. Davies, Michael Marcus, Michael Liu, Geoffrey Caporaso, Neil E. Christiani, David C. Wei, Yongyue Chen, Chu Doherty, Jennifer A. Severi, Gianluca Goodman, Gary E. Hung, Rayjean J. Amos, Christopher I. McKay, James Johansson, Mattias Brennan, Paul TI The causal relevance of body mass index in different histological types of lung cancer: A Mendelian randomization study SO SCIENTIFIC REPORTS LA English DT Article ID RISK; METAANALYSIS; ASSOCIATION; POPULATION; VARIANTS; INSIGHTS; OBESITY AB Body mass index (BMI) is inversely associated with lung cancer risk in observational studies, even though it increases the risk of several other cancers, which could indicate confounding by tobacco smoking or reverse causality. We used the two-sample Mendelian randomization (MR) approach to circumvent these limitations of observational epidemiology by constructing a genetic instrument for BMI, based on results from the GIANT consortium, which was evaluated in relation to lung cancer risk using GWAS results on 16,572 lung cancer cases and 21,480 controls. Results were stratified by histological subtype, smoking status and sex. An increase of one standard deviation (SD) in BMI (4.65 Kg/m(2)) raised the risk for lung cancer overall (OR = 1.13; P = 0.10). This was driven by associations with squamous cell (SQ) carcinoma (OR = 1.45; P = 1.2 x 10(-3)) and small cell (SC) carcinoma (OR = 1.81; P = 0.01). An inverse trend was seen for adenocarcinoma (AD) (OR = 0.82; P = 0.06). In stratified analyses, a 1 SD increase in BMI was inversely associated with overall lung cancer in never smokers (OR = 0.50; P = 0.02). These results indicate that higher BMI may increase the risk of certain types of lung cancer, in particular SQ and SC carcinoma. C1 [Carreras-Torres, Robert; McKay, James; Johansson, Mattias; Brennan, Paul] IARC, Genet Sect, Lyon, France. [Haycock, Philip C.; Relton, Caroline L.; Martin, Richard M.; Smith, George Davey] Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol, Avon, England. [Martin, Richard M.] Univ Hosp Bristol NHS Fdn Trust, Natl Inst Hlth Res, Biomed Res Unit Nutr Diet & Lifestyle, Bristol BS2 8AE, Avon, England. [Martin, Richard M.] Univ Bristol, Bristol BS2 8AE, Avon, England. [Kraft, Peter; Gao, Chi; Tworoger, Shelley; Christiani, David C.; Wei, Yongyue] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Tworoger, Shelley] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Tworoger, Shelley] Harvard Med Sch, Boston, MA USA. [Le Marchand, Loic; Wilkens, Lynne R.] Univ Hawaii, Ctr Canc, Epidemiol Program, Honolulu, HI 96822 USA. [Park, Sungshim L.; Haiman, Christopher] Univ Southern Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Field, John K.; Davies, Michael; Marcus, Michael] Univ Liverpool, Inst Translat Med, Dept Mol & Clin Canc Med, Roy Castle Lung Canc Res Programme,Canc Res Ctr, Liverpool, Merseyside, England. [Liu, Geoffrey] Princess Margaret Canc Ctr, Ontario Canc Inst, Toronto, ON, Canada. [Caporaso, Neil E.] NCI, Genet Epidemiol Branch, DCEG, NIH, Rockville, MD USA. [Christiani, David C.; Wei, Yongyue] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Christiani, David C.; Wei, Yongyue] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. [Chen, Chu] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, 1124 Columbia St, Seattle, WA 98104 USA. [Doherty, Jennifer A.] Dartmouth Coll, Geisel Sch Med, Dept Epidemiol, 1 Med Ctr Dr, Lebanon, NH 03756 USA. [Severi, Gianluca] Human Genet Fdn HuGeF, Turin, Italy. [Goodman, Gary E.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Hung, Rayjean J.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada. [Amos, Christopher I.] Dartmouth Coll, Geisel Sch Med, Dept Biomed Data Sci, 1 Med Ctr Dr, Lebanon, NH 03756 USA. RP Brennan, P (reprint author), IARC, Genet Sect, Lyon, France. EM gep@iarc.fr RI Liu, Geoffrey/N-4421-2016; Hung, Rayjean/A-7439-2013; Davey Smith, George/A-7407-2013 OI Davey Smith, George/0000-0002-1407-8314 FU Cancer Research UK [C18281/A19169, C52724/A20138]; National Institute for Health Research (NIHR) Bristol Nutritional Biomedical Research Unit at University Hospitals Bristol NHS Foundation Trust; University of Bristol; MRC Integrative Epidemiology Unit at the University of Bristol [MC_UU_12013/1, MC_UU_12013/2]; NCI [UM1 CA186107, P01 CA87969, R01 CA49449, UM1 CA167552] FX RCT, PCH, CLR, RMM, GDS, MJ, and PB are investigators or researchers on a Cancer Research UK (C18281/A19169) Programme Grant (the Integrative Cancer Epidemiology Programme). RMM is supported by the National Institute for Health Research (NIHR) Bristol Nutritional Biomedical Research Unit based at University Hospitals Bristol NHS Foundation Trust and the University of Bristol. CLR and GDS are supported by funding from the MRC Integrative Epidemiology Unit at the University of Bristol (MC_UU_12013/1, MC_UU_12013/2). PCH is supported by a Cancer Research UK Population Research Postdoctoral Fellowship (C52724/A20138). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. NCI grants: UM1 CA186107, P01 CA87969, R01 CA49449, UM1 CA167552. We would like to thank the participants and staff of the NHS and HPFS for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data. NR 24 TC 1 Z9 1 U1 4 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD AUG 4 PY 2016 VL 6 AR 31121 DI 10.1038/srep31121 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DS7MB UT WOS:000380966500001 PM 27487993 ER PT J AU DiGiovanni, CW Lin, SS Daniels, TR Glazebrook, M Evangelista, P Donahue, R Beasley, W Baumhauer, JF AF DiGiovanni, Christopher W. Lin, Sheldon S. Daniels, Timothy R. Glazebrook, Mark Evangelista, Peter Donahue, Rafe Beasley, William Baumhauer, Judith F. TI The Importance of Sufficient Graft Material in Achieving Foot or Ankle Fusion SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID AUTOGENOUS BONE-GRAFT; RETROGRADE INTRAMEDULLARY NAIL; TIBIOTALOCALCANEAL ARTHRODESIS; SUBTALAR ARTHRODESIS; COMPUTED-TOMOGRAPHY; FLATFOOT DEFORMITY; HINDFOOT FUSIONS; PROXIMAL TIBIA; RHPDGF-BB; FIXATION AB Background: Nonunion, an important complication following foot and ankle arthrodesis, causes substantial morbidity and disability. In patients undergoing hindfoot and ankle arthrodesis, autogenous bone graft (autograft) or a suitable alternative is often used to promote osseous fusion across the joint. This study assessed the importance of adequate graft material in the fusion space to achieve joint fusion during ankle and hindfoot arthrodesis. Methods: This study used data from a previously published clinical trial of grafting material (recombinant human platelet-derived growth factor-BB with beta-tricalcium phosphate [rhPDGF-BB/beta-TCP] or autograft) for healing in hindfoot and ankle arthrodesis to correlate the amount of graft fill at 9 weeks with ultimate healing. Patients who received supplemental graft material for ankle or hindfoot arthrodesis for end-stage ankle or hindfoot arthritis were stratified according to nonunion risk factors and surgical fusion site. Patients underwent arthrodesis using standard rigid internal fixation. Graft fill was defined as "adequate" if the material occupied >= 50% of the cross-sectional area of the fusion space on a computed tomography (CT) scan made at 9 weeks. Fusion was defined as osseous bridging of >= 50% of each articulation on a CT scan made at 24 weeks. Three hundred and seventy-nine patients with 573 joints (383 managed with rhPDGF-BB/b-TCP and 190 managed with autograft) that underwent arthrodesis had complete follow-up with 9-week and 24-week CT scans available. Results: Overall, 472 (82%) of 573 joints had adequate graft fill; of those, 383 (81%) were successfully fused at 24 weeks compared with 21 (21%) of 101 joints without adequate graft fill (p < 0.0001). Absolute fusion rate differences (joints with adequate fill minus those without adequate fill) were consistent across joints (61% to 63%) and for graft materials. The overall odds ratio (OR) of successful fusion in joints with adequate graft fill compared with those without adequate graft fill was 16.4 (95% confidence interval, 9.6 to 27.9). Conclusions: This study demonstrates an association between the amount of graft material and successful hindfoot and ankle arthrodesis. Graft material filling of >= 50% of the fusion space at 9 weeks, regardless of type or origin, was associated with significantly higher fusion rates at 24 weeks. C1 [DiGiovanni, Christopher W.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Lin, Sheldon S.] Rutgers New Jersey Med Sch, North Jersey Orthopaed Inst, Newark, NJ USA. [Daniels, Timothy R.] St Michaels Hosp, Div Orthopaed Surg, Toronto, ON, Canada. [Daniels, Timothy R.] Univ Toronto, Dept Surg, Toronto, ON, Canada. [Glazebrook, Mark] Dalhousie Univ, Halifax, NS, Canada. [Glazebrook, Mark] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. [Evangelista, Peter] Brown Univ, Rhode Isl Hosp, Warren Alpert Sch Med, Dept Diagnost Imaging, Providence, RI 02903 USA. [Donahue, Rafe; Beasley, William] Wright Med Technol Inc, Franklin, TN USA. [Baumhauer, Judith F.] Univ Rochester, Sch Med, Dept Orthopaed, Rochester, NY USA. RP DiGiovanni, CW (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. EM CWDiGiovanni@MGH.Harvard.edu FU BioMimetic Therapeutics, Inc. FX Two authors, the statistician (R.D.) and the certified clinical research professional responsible for organizational management of the study (W.B.), are employees of BioMimetic Therapeutics, Inc. (Wright Medical, Inc.); both were blinded to treatment assignments in the parent clinical trial until after the database had been locked and the analysis plan finalized. The remaining authors received funding from BioMimetic Therapeutics, Inc. to cover research costs and/or were working as consultants for BioMimetic Therapeutics, Inc. The sponsor did not control the drafting and writing of the manuscript. On the Disclosure of Potential Conflicts of Interest forms, which are provided with the online version of the article, one or more of the authors checked "yes" to indicate that the author had a relevant financial relationship in the biomedical arena outside the submitted work and "yes" to indicate that the author had other relationships or activities that could be perceived to influence, or have the potential to influence, what was written in this work. NR 31 TC 1 Z9 1 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02492 USA SN 0021-9355 EI 1535-1386 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD AUG 3 PY 2016 VL 98 IS 15 BP 1260 EP 1267 DI 10.2106/JBJS.15.00879 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA EN4AP UT WOS:000395949900008 PM 27489316 ER PT J AU Parkkinen, M Madanat, R Lindahl, J Makinen, TJ AF Parkkinen, Markus Madanat, Rami Lindahl, Jan Makinen, Tatu J. TI Risk Factors for Deep Infection Following Plate Fixation of Proximal Tibial Fractures SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID SURGICAL SITE INFECTION; COMPARTMENT SYNDROME; OPERATIVE TREATMENT; INCISION FASCIOTOMY; EXTERNAL FIXATION; COMPLICATIONS; MANAGEMENT; SURGERY AB Background: The risk factors are unclear for deep surgical site infection after plate fixation of proximal tibial fractures. The objective of this study was to identify the patient and surgical procedure-related risk factors for infection using established criteria for deep surgical site infection. Methods: A total of 655 proximal tibial fractures were treated with open reduction and plate fixation at our center between 2004 and 2013. We identified 34 patients with deep surgical site infection. A control group of 136 patients was randomly selected from the non-infected cohort. Potential risk factors for deep surgical site infection were identified by reviewing surgical, medical, and radiographic records. Independent risk factors for infection were identified from multivariable logistic regression analysis using a stepwise procedure. Results: The prevalence of deep surgical site infection was 5.2%, the mean age of affected patients was 55 years (range, 16 to 84 years), and 35% of patients were female. Twenty-eight of 34 deep infections were diagnosed within 2 months (acute onset), and only 6 infections were diagnosed >6 months after the index surgical procedure. Nine of the 28 acuteonset infections were treated with antibiotic therapy and debridement. Seventeen patients (50%) required muscle flap coverage, and 5 patients (15%) eventually required above-the-knee amputation. In the multivariable logistic regression analysis with odds ratios (ORs) and 95% confidence intervals (95% CIs), independent predictors of infection were patient age of >= 50 years (OR, 3.6 [95% CI, 1.3 to 10.1]); obesity, defined as a body mass index of >= 30 kg/m(2) (OR, 6.5 [95% CI, 2.2 to 18.9]); alcohol abuse (OR, 6.7 [95% CI, 2.4 to 19.2]); OTA/AO-type-C fracture (OR, 2.8 [95% CI, 1.1 to 7.5]); use of a temporary spanning external fixator (OR, 3.9 [95% CI, 1.4 to 11.1]); and a 4-compartment fasciotomy (OR, 4.5 [95% CI, 1.3 to 15.7]). Conclusions: There is high morbidity associated with deep surgical site infection in plated proximal tibial fractures. Patients who are >= 50 years of age, obese patients, those with a history of alcohol abuse, or those with an OTA/AO-type-C fracture are at high risk for infection. Performing a fasciotomy also increases the risk of deep infection and should be implemented with meticulous technique when deemed necessary. C1 [Parkkinen, Markus; Lindahl, Jan] Univ Helsinki, Dept Orthopaed & Traumatol, Helsinki, Finland. [Parkkinen, Markus; Lindahl, Jan] Helsinki Univ Hosp, Helsinki, Finland. [Madanat, Rami] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. [Madanat, Rami] Harvard Med Sch, Boston, MA USA. [Makinen, Tatu J.] Mt Sinai Hosp, Div Orthopaed Surg, Toronto, ON, Canada. [Makinen, Tatu J.] Univ Toronto, Toronto, ON, Canada. RP Parkkinen, M (reprint author), Univ Helsinki, Dept Orthopaed & Traumatol, Helsinki, Finland.; Parkkinen, M (reprint author), Helsinki Univ Hosp, Helsinki, Finland. EM markus.parkkinen@hus.fi NR 30 TC 0 Z9 0 U1 1 U2 1 PU JOURNAL BONE JOINT SURGERY PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02492 USA SN 0021-9355 EI 1535-1386 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD AUG 3 PY 2016 VL 98 IS 15 BP 1292 EP 1297 DI 10.2106/JBJS.15.00894 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA EN4AP UT WOS:000395949900012 PM 27489320 ER PT J AU Georgitsi, M Willsey, AJ Mathews, CA State, M Scharf, JM Paschou, P AF Georgitsi, Marianthi Willsey, A. Jeremy Mathews, Carol A. State, Matthew Scharf, Jeremiah M. Paschou, Peristera TI The Genetic Etiology of Tourette Syndrome: Large-Scale Collaborative Efforts on the Precipice of Discovery SO FRONTIERS IN NEUROSCIENCE LA English DT Article DE Gilles de la Tourette syndrome; genetics of complex disorders; neurodevelopmental disorders; GWAS (genomewide association study); gene-environment interactions; next generation sequencing; collaborative studies ID OBSESSIVE-COMPULSIVE DISORDER; AUTISM SPECTRUM DISORDER; COPY NUMBER VARIANTS; FAMILY-BASED SAMPLE; NEUROPSYCHIATRIC DISORDERS; BASAL GANGLIA; TRANSLOCATION BREAKPOINT; HISTIDINE-DECARBOXYLASE; DOPAMINERGIC GENES; RECEPTOR LOCUS AB Gilles de la Tourette Syndrome (TS) is a childhood-onset neurodevelopmental disorder that is characterized by multiple motor and phonic tics. It has a complex etiology with multiple genes likely interacting with environmental factors to lead to the onset of symptoms. The genetic basis of the disorder remains elusive. However, multiple resources and large-scale projects are coming together, launching a new era in the field and bringing us on the verge of discovery. The large-scale efforts outlined in this report are complementary and represent a range of different approaches to the study of disorders with complex inheritance. The Tourette Syndrome Association International Consortium for Genetics (TSAICG) has focused on large families, parent-proband trios and cases for large case-control designs such as genomewide association studies (GWAS), copy number variation (CNV) scans, and exome/genome sequencing. TIC Genetics targets rare, large effect size mutations in simplex trios, and multigenerational families. The European Multicentre Tics in Children Study (EMTICS) seeks to elucidate gene environment interactions including the involvement of infection and immune mechanisms in TS etiology. Finally, TS-EUROTRAIN, a Marie Curie Initial Training Network, aims to act as a platform to unify large-scale projects in the field and to educate the next generation of experts. Importantly, these complementary large-scale efforts are joining forces to uncover the full range of genetic variation and environmental risk factors for TS, holding great promise for identifying definitive TS susceptibility genes and shedding light into the complex pathophysiology of this disorder. C1 [Georgitsi, Marianthi; Paschou, Peristera] Democritus Univ Thrace, Dept Mol Biol & Genet, Alexandroupolis, Greece. [Georgitsi, Marianthi] Aristotle Univ Thessaloniki, Dept Med, Thessaloniki, Greece. [Willsey, A. Jeremy; State, Matthew] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Mathews, Carol A.] Univ Florida, Dept Psychiat, Sch Med, Gainesville, FL 32611 USA. [Scharf, Jeremiah M.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. [Scharf, Jeremiah M.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. RP Paschou, P (reprint author), Democritus Univ Thrace, Dept Mol Biol & Genet, Alexandroupolis, Greece.; State, M (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.; Scharf, JM (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA.; Scharf, JM (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. EM matthew.state@ucsf.edu; jscharf@partners.org; ppaschou@mbg.duth.gr FU European Union under the Seventh Framework People Programme (TS-EUROTRAIN (FP7-PEOPLE-ITN)) [316978-EMTICS (FP7/2007-2013), 278367]; NIH [U01NS40024, U01NS40024-09S1, K23MH085057, R01MH096767, K02NS085048, R01MH092290, R01 MH092291, R01MH092292, R01MH092293, R01MH092513, R01MH092516, R01 MH092520, R01MH092289, U24MH068457]; Tourette Association of America; New Jersey Center for Tourette Syndrome and Associated Disorders (NJCTS) FX EMTICS and TS-EUROTRAIN are funded by the European Union under the Seventh Framework People Programme (TS-EUROTRAIN (FP7-PEOPLE-2012-ITN), Grant Agr.No.316978-EMTICS (FP7/2007-2013), Grant Agr.No. 278367). TSAICG is funded by NIH U01NS40024, U01NS40024-09S1, K23MH085057, R01MH096767, K02NS085048, and research funding from the Tourette Association of America. TIC Genetics is funded by NIH (R01MH092290; R01 MH092291; R01MH092292; R01MH092293; R01MH092513; R01MH092516; R01 MH092520; R01MH092289; U24MH068457) and the New Jersey Center for Tourette Syndrome and Associated Disorders (NJCTS). NR 79 TC 3 Z9 3 U1 9 U2 13 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1662-453X J9 FRONT NEUROSCI-SWITZ JI Front. Neurosci. PD AUG 3 PY 2016 VL 10 AR 351 DI 10.3389/fnins.2016.00357 PG 9 WC Neurosciences SC Neurosciences & Neurology GA DS9EQ UT WOS:000381086000001 PM 27536211 ER PT J AU Yong, KJ Basseres, DS Welner, RS Zhang, WC Yang, H Yan, B Alberich-Jorda, M Zhang, JY de Figueiredo-Pontes, LL Battelli, C Hetherington, CJ Ye, M Zhang, H Maroni, G O'Brien, K Magli, MC Borczuk, AC Varticovski, L Kocher, O Zhang, P Moon, YC Sydorenko, N Cao, LX Davis, TW Thakkar, BM Soo, RA Iwama, A Lim, B Halmos, B Neuberg, D Tenen, DG Levantini, E AF Yong, Kol Jia Basseres, Daniela S. Welner, Robert S. Zhang, Wen Cai Yang, Henry Yan, Benedict Alberich-Jorda, Meritxell Zhang, Junyan de Figueiredo-Pontes, Lorena Lobo Battelli, Chiara Hetherington, Christopher J. Ye, Min Zhang, Hong Maroni, Giorgia O'Brien, Karen Magli, Maria Cristina Borczuk, Alain C. Varticovski, Lyuba Kocher, Olivier Zhang, Pu Moon, Young-Choon Sydorenko, Nadiya Cao, Liangxian Davis, Thomas W. Thakkar, Bhavin M. Soo, Ross A. Iwama, Atsushi Lim, Bing Halmos, Balazs Neuberg, Donna Tenen, Daniel G. Levantini, Elena TI Targeted BMI1 inhibition impairs tumor growth in lung adenocarcinomas with low CEBP alpha expression SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID CCAAT/ENHANCER-BINDING-PROTEIN; ACUTE MYELOID-LEUKEMIA; FACTOR-C/EBP-ALPHA; POSTTRANSCRIPTIONAL CONTROL; ADJUVANT CHEMOTHERAPY; CELL-PROLIFERATION; DOWN-REGULATION; DRUG DISCOVERY; GENE SIGNATURE; SELF-RENEWAL AB Lung cancer is the most common cause of cancer deaths. The expression of the transcription factor C/EBP alpha (CCAAT/enhancer binding protein a) is frequently lost in non-small cell lung cancer, but the mechanisms by which C/EBP alpha suppresses tumor formation are not fully understood. In addition, no pharmacological therapy is available to specifically target C/EBP alpha expression. We discovered a subset of pulmonary adenocarcinoma patients in whom negative/low C/EBP alpha expression and positive expression of the oncogenic protein BMI1 (B lymphoma Mo-MLV insertion region 1 homolog) have prognostic value. We also generated a lung-specific mouse model of C/EBP alpha deletion that develops lung adenocarcinomas, which are prevented by Bmi1 haploinsufficiency. BMI1 activity is required for both tumor initiation and maintenance in the C/EBP alpha-null background, and pharmacological inhibition of BMI1 exhibits antitumor effects in both murine and human adenocarcinoma lines. Overall, we show that C/EBP alpha is a tumor suppressor in lung cancer and that BMI1 is required for the oncogenic process downstream of C/EBP alpha loss. Therefore, anti-BMI1 pharmacological inhibition may offer a therapeutic benefit for lung cancer patients with low expression of C/EBP alpha and high BMI1. C1 [Yong, Kol Jia; Yang, Henry; Thakkar, Bhavin M.; Soo, Ross A.; Tenen, Daniel G.] Natl Univ Singapore, Canc Sci Inst, Singapore 117599, Singapore. [Basseres, Daniela S.] Univ Sao Paulo, Inst Chem, Biochem Dept, BR-05508 Sao Paulo, Brazil. [Basseres, Daniela S.; Welner, Robert S.; Zhang, Wen Cai; Alberich-Jorda, Meritxell; Zhang, Junyan; de Figueiredo-Pontes, Lorena Lobo; Battelli, Chiara; Hetherington, Christopher J.; Ye, Min; Zhang, Hong; O'Brien, Karen; Kocher, Olivier; Zhang, Pu; Lim, Bing; Levantini, Elena] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Basseres, Daniela S.; Welner, Robert S.; Zhang, Wen Cai; Alberich-Jorda, Meritxell; Zhang, Junyan; de Figueiredo-Pontes, Lorena Lobo; Battelli, Chiara; Hetherington, Christopher J.; Ye, Min; Zhang, Hong; O'Brien, Karen; Kocher, Olivier; Zhang, Pu; Lim, Bing; Tenen, Daniel G.; Levantini, Elena] Harvard Med Sch, Boston, MA 02215 USA. [Basseres, Daniela S.; Welner, Robert S.; Alberich-Jorda, Meritxell; Zhang, Junyan; de Figueiredo-Pontes, Lorena Lobo; Hetherington, Christopher J.; Ye, Min; Zhang, Hong; O'Brien, Karen; Zhang, Pu; Tenen, Daniel G.; Levantini, Elena] Harvard Stem Cell Inst, Boston, MA 02215 USA. [Welner, Robert S.] Univ Alabama Birmingham, Div Hematol & Oncol, Dept Med, Birmingham, AL 35233 USA. [Zhang, Wen Cai; Lim, Bing] Genome Inst Singapore, Stem Cell & Dev Biol, Singapore 138672, Singapore. [Yan, Benedict] KK Womens & Childrens Hosp, Dept Pathol & Lab Med, Singapore 119074, Singapore. [Alberich-Jorda, Meritxell] ASCR, Inst Mol Genet, Prague 14200, Czech Republic. [de Figueiredo-Pontes, Lorena Lobo] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, Hematol Div, BR-14020 Sao Paulo, Brazil. [Maroni, Giorgia; Magli, Maria Cristina; Levantini, Elena] Natl Res Council CNR, Inst Biomed Technol, I-56124 Pisa, Italy. [Borczuk, Alain C.] Weill Cornell Univ, Med Ctr, Dept Pathol, New York, NY 10065 USA. [Varticovski, Lyuba] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20817 USA. [Moon, Young-Choon; Sydorenko, Nadiya; Cao, Liangxian; Davis, Thomas W.] PTC Therapeut, 100 Corp Court, South Plainfield, NJ 07080 USA. [Soo, Ross A.] Univ Western Australia, Dept Hematol Oncol, Crawley, WA 6009, Australia. [Iwama, Atsushi] Chiba Univ, Grad Sch Med, Dept Cellular & Mol Med, Chiba 2608670, Japan. [Halmos, Balazs] Montefiore Hosp, Div Hematol Oncol, Bronx, NY 10461 USA. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Battelli, Chiara] New England Canc Specialists, Scarborough, ME 04074 USA. [O'Brien, Karen] Novartis Inst BioMed Res Inc, Cambridge, MA 02176 USA. [Lim, Bing] Merck Res Labs, Translat Med Res Ctr, Singapore 138665, Singapore. RP Tenen, DG (reprint author), Natl Univ Singapore, Canc Sci Inst, Singapore 117599, Singapore.; Levantini, E (reprint author), Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.; Tenen, DG; Levantini, E (reprint author), Harvard Med Sch, Boston, MA 02215 USA.; Tenen, DG; Levantini, E (reprint author), Harvard Stem Cell Inst, Boston, MA 02215 USA.; Levantini, E (reprint author), Natl Res Council CNR, Inst Biomed Technol, I-56124 Pisa, Italy. EM csidgt@nus.edu.sg; elevanti@bidmc.harvard.edu RI Basseres, Daniela/C-6623-2013 OI Basseres, Daniela/0000-0001-7745-3567 FU NIH/NCI (National Cancer Institute) Project 2 grant [P50 CA90578]; NCIS (National University Cancer Institute of Singapore) Yong Siew Yoon Research grant; Singapore Ministry of Health's National Medical Research Council under its Singapore Translational Research (STaR) Investigator Award; National Research Foundation of Singapore; Singapore Ministry of Education under its Research Centres of Excellence initiative Project 3 [PO1 CA66996, 1R35CA197697]; FAMRI (Flight Attendant Medical Research Institute) YCSA (Young Clinical Scientist Award) [052409]; FAMRI CIA (Clinical Innovator Awards) [103063]; FAMRI YCSA [072165]; Doctors Cancer Foundation Award; IASLC (International Association for the Study of Lung Cancer) Award; MIUR (Ministry of Education, University and Research) Flagship InterOmics Project; MSMT Navrat grant [LK21307]; Jose Carreras fellowship [FIJC-10]; NCI [T32/K12/R25]; Agency for Science, Technology and Research (A*STAR), Singapore; National Medical Research Council of Singapore [NMRC/CG/NCIS/2010]; Dana-Farber/Harvard Cancer Center support grant [5P30 CA006516] FX This work was funded by NIH/NCI (National Cancer Institute) P50 CA90578 Project 2 grant (to D.G.T. and B.H.); the NCIS (National University Cancer Institute of Singapore) Yong Siew Yoon Research grant through donations from the Yong Loo Lin Trust, the Singapore Ministry of Health's National Medical Research Council under its Singapore Translational Research (STaR) Investigator Award, and the National Research Foundation of Singapore and the Singapore Ministry of Education under its Research Centres of Excellence initiative and PO1 CA66996 Project 3 and 1R35CA197697 grants (to D.G.T.); FAMRI (Flight Attendant Medical Research Institute) YCSA (Young Clinical Scientist Award) 052409 and FAMRI CIA (Clinical Innovator Awards) 103063 (to E.L.); FAMRI YCSA 072165 (to D.S.B.); Doctors Cancer Foundation Award (to E.L.); IASLC (International Association for the Study of Lung Cancer) Award (to E.L.); MIUR (Ministry of Education, University and Research) Flagship InterOmics Project (to E.L. and M.C.M.); and MSMT Navrat grant LK21307 (to M.-A.J.). R.S.W. was supported by a Jose Carreras fellowship, FIJC-10. C.B. was supported by an NCI T32/K12/R25 award. W.C.Z. and B.L.'s work was supported by Agency for Science, Technology and Research (A*STAR), Singapore. R.A.S. was supported by the National Medical Research Council of Singapore (NMRC/CG/NCIS/2010). D.N. was supported by Dana-Farber/Harvard Cancer Center support grant 5P30 CA006516. NR 50 TC 1 Z9 1 U1 4 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD AUG 3 PY 2016 VL 8 IS 350 AR 350ra104 DI 10.1126/scitranslmed.aad6066 PG 10 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA DS4VP UT WOS:000380780000006 PM 27488898 ER PT J AU Goel, S Zhao, JJ AF Goel, Shom Zhao, Jean J. TI CDK4/6 inhibition: the late harvest cycle begins SO ONCOTARGET LA English DT Editorial Material DE CDK4/6; cyclin; cell cycle; cancer; abemaciclib ID CANCER C1 [Goel, Shom] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Zhao, Jean J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Zhao, Jean J.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Zhao, Jean J.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. RP Goel, S (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.; Zhao, JJ (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.; Zhao, JJ (reprint author), Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.; Zhao, JJ (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. EM shom_goel@dfci.har-vard.edu; Jean_Zhao@dfci.harvard.edu NR 7 TC 0 Z9 0 U1 1 U2 1 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD AUG 2 PY 2016 VL 7 IS 31 BP 48854 EP 48856 DI 10.18632/oncotarget.9576 PG 3 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DY8ZS UT WOS:000385422000002 PM 27391058 ER PT J AU Jiang, XN Niu, MM Chen, DS Chen, J Cao, Y Li, XR Ying, HQ Bergholz, J Zhang, YJ Xiao, ZX AF Jiang, Xinni Niu, MengMeng Chen, Deshi Chen, Jing Cao, Yang Li, Xiaorong Ying, Haoqiang Bergholz, Johann Zhang, Yujun Xiao, Zhi-Xiong TI Inhibition of Cdc42 is essential for Mig-6 suppression of cell migration induced by EGF SO ONCOTARGET LA English DT Article DE Mig-6; Cdc42; EGF; migration ID GROUP-II PAKS; BREAST-CANCER; LUNG-CANCER; RHO GTPASES; ENDOGENOUS INHIBITOR; NEGATIVE REGULATOR; KINASE DOMAIN; E-CADHERIN; IN-VIVO; EXPRESSION AB The adaptor protein Mig-6 is a negative regulator of EGF signaling. It is shown that Mig-6 inhibits cell migration via direct interaction with the ErbB receptors, thereby inhibiting cross-phosphorylation or targeting the receptors for degradation. Mig-6 has also been shown to bind to and inhibit the Rho GTPase Cdc42 to suppress cytoskeletal rearrangement. However, the molecular mechanism(s) by which Mig-6 inhibits cell migration via Cdc42 is still not entirely clear. Here, we show that Mig-6 binding to Cdc42 is necessary and sufficient to inhibit EGF-induced filopodia formation and migration. This binding, mediated by four specific residues (I11, R12, M26, R30) in the Mig-6 CRIB domain, is essential for Mig-6 function. In addition, ectopic expression of Cdc42 reverses Mig-6 inhibition of cell migration. Mig-6 CRIB domain, alone, is sufficient to inhibit cell migration. Conversely, Mig-6 binding to EGFR is dispensable for Mig-6-mediated inhibition of cell migration. Moreover, we found that decreased Mig-6 expression correlates with cancer progression in breast and prostate cancers. Together, our results demonstrate that Mig-6 inhibition of Cdc42 signaling is critical in Mig-6 function to suppress cell migration and that dysregulation of this pathway may play a critical role in cancer development. C1 [Jiang, Xinni; Niu, MengMeng; Chen, Deshi; Chen, Jing; Cao, Yang; Li, Xiaorong; Bergholz, Johann; Zhang, Yujun; Xiao, Zhi-Xiong] Sichuan Univ, Coll Life Sci, Ctr Growth Metab & Aging, Key Lab Bioresource & Ecoenvironm,Minist Educ, Chengdu 610014, Peoples R China. [Ying, Haoqiang] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Bergholz, Johann] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Xiao, ZX (reprint author), Sichuan Univ, Coll Life Sci, Ctr Growth Metab & Aging, Key Lab Bioresource & Ecoenvironm,Minist Educ, Chengdu 610014, Peoples R China. EM jimzx@scu.edu.cn FU National Key Basic Research Program (973 Program) of China [2012CB910700]; National Natural Science Foundation of China (NSFC) [81330054, 31171362]; NSFC [31350110216] FX This work was supported by the National Key Basic Research Program (973 Program) of China (2012CB910700), National Natural Science Foundation of China (NSFC) grant (81330054 and 31171362) to Z-X. X., and NSFC grant (31350110216) to J.B. NR 49 TC 0 Z9 0 U1 2 U2 2 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD AUG 2 PY 2016 VL 7 IS 31 BP 49180 EP 49193 DI 10.18632/oncotarget.10205 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DY8ZS UT WOS:000385422000029 PM 27341132 ER PT J AU Brundin, L Sellgren, CM Lim, CK Grit, J Palsson, E Landen, M Samuelsson, M Lundgren, K Brundin, P Fuchs, D Postolache, TT Traskman-Bendz, L Guillemin, GJ Erhardt, S AF Brundin, L. Sellgren, C. M. Lim, C. K. Grit, J. Palsson, E. Landen, M. Samuelsson, M. Lundgren, K. Brundin, P. Fuchs, D. Postolache, T. T. Traskman-Bendz, L. Guillemin, G. J. Erhardt, S. TI An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation SO TRANSLATIONAL PSYCHIATRY LA English DT Article ID MAJOR DEPRESSIVE DISORDER; EPSILON-SEMIALDEHYDE DECARBOXYLASE; HIGH-PROTEIN DIET; QUINOLINIC ACID; PICOLINIC-ACID; CHROMIUM PICOLINATE; ASSESSMENT SCALE; CONTROLLED-TRIAL; TRYPTOPHAN; RAT AB Emerging evidence suggests that inflammation has a key role in depression and suicidal behavior. The kynurenine pathway is involved in neuroinflammation and regulates glutamate neurotransmission. In the cerebrospinal fluid (CSF) of suicidal patients, levels of inflammatory cytokines and the kynurenine metabolite quinolinic acid (QUIN), an N-methyl-D-aspartate receptor agonist, are increased. The enzyme amino-beta-carboxymuconate-semialdehyde-decarboxylase (ACMSD) limits QUIN formation by competitive production of the neuroprotective metabolite picolinic acid (PIC). Therefore, decreased ACMSD activity can lead to excess QUIN. We tested the hypothesis that deficient ACMSD activity underlies suicidal behavior. We measured PIC and QUIN in CSF and plasma samples from 137 patients exhibiting suicidal behavior and 71 healthy controls. We used DSM-IV and the Montgomery-Asberg Depression Rating Scale and Suicide Assessment Scale to assess behavioral changes. Finally, we genotyped ACMSD tag single nucleotide polymorphisms (SNPs) in 77 of the patients and 150 population-based controls. Suicide attempters had reduced PIC and a decreased PIC/QUIN ratio in both CSF (P<0.001) and blood (P=0.001 and P<0.01, respectively). The reductions of PIC in CSF were sustained over 2 years after the suicide attempt based on repeated measures. The minor C allele of the ACMSD SNP rs2121337 was more prevalent in suicide attempters and associated with increased CSF QUIN. Taken together, our data suggest that increased QUIN levels may result from reduced activity of ACMSD in suicidal subjects. We conclude that measures of kynurenine metabolites can be explored as biomarkers of suicide risk, and that ACMSD is a potential therapeutic target in suicidal behavior. C1 [Brundin, L.; Grit, J.; Brundin, P.] Van Andel Res Inst, Ctr Neurodegenerat Sci, 3rd Floor,333 Bostwick Ave NE, Grand Rapids, MI 49503 USA. [Sellgren, C. M.; Samuelsson, M.; Erhardt, S.] Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden. [Sellgren, C. M.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Sellgren, C. M.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA USA. [Lim, C. K.; Guillemin, G. J.] Macquarie Univ, Fac Med & Hlth Sci, Sydney, NSW, Australia. [Palsson, E.; Landen, M.] Gothenburg Univ, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden. [Samuelsson, M.; Lundgren, K.] Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden. [Fuchs, D.] Med Univ Innsbruck, Div Biol Chem, Ctr Chem & Biomed, Innsbruck, Austria. [Postolache, T. T.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. [Postolache, T. T.] Rocky Mt MIRECC, Denver, CO USA. [Traskman-Bendz, L.] Lund Univ, Dept Clin Sci, Sect Psychiat, Lund, Sweden. [Guillemin, G. J.] NHMRC Ctr Res Excellence Suicide Prevent CRESP, Randwick, NSW, Australia. RP Grit, J (reprint author), Van Andel Res Inst, Ctr Neurodegenerat Sci, 3rd Floor,333 Bostwick Ave NE, Grand Rapids, MI 49503 USA. EM jamie.grit@vai.org FU Swedish Research Council (VR) [2009-4284, 2011-4787, 2002-5297, 2008-2922, 2009-7052, 2013-2838]; Province of Scania clinical state grants; Swedish Research Council [K2014-62X-14647-12-51]; Swedish Federal Government [ALF 20130032]; NIH [1R01MH104622-01]; American Foundation for Suicide Prevention [DIG 1-162-12]; Michigan State University; Van Andel Research Institute; Australian Research Council; National Health and Medical Research Council, Australia; Rocky Mountain MIRECC; Merit Review CSRD grant [1 I01 CX001310- 01A1]; Joint Institute for Food Safety and Applied Nutrition/ UMD [FDU.001418] FX We acknowledge Zachary Madaj at the VARI core of bioinformatics and statistics for the conduct of the longitudinal data analysis in this study. The design of this study, collection of patient samples and data analysis was funded by the Swedish Research Council (VR), no. 2009-4284 and 2011-4787 (LB), 2002-5297 and 2008-2922 (LT-B), 2009-7052 and 2013-2838 (SE), as well as the Province of Scania clinical state grants (LB and LT-B). The collection of population-based controls was funded by the Swedish Research Council (K2014-62X-14647-12-51) and the Swedish Federal Government under the LUA/ALF agreement (ALF 20130032). Laboratory analyses of the samples and data interpretation were also supported by NIH 1R01MH104622-01 and a Distinguished Investigator Award from the American Foundation for Suicide Prevention (DIG 1-162-12; TTP and LB), Michigan State University and Van Andel Research Institute (LB); the Australian Research Council and the National Health and Medical Research Council, Australia (GJG), as well as and in part by the Rocky Mountain MIRECC (TTP), the Merit Review CSR&D grant 1 I01 CX001310- 01A1 (TTP and LB) and the Joint Institute for Food Safety and Applied Nutrition/ UMD through the cooperative agreement FDU.001418 (TTP). NR 54 TC 3 Z9 3 U1 4 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2158-3188 J9 TRANSL PSYCHIAT JI Transl. Psychiatr. PD AUG 2 PY 2016 VL 6 AR e865 DI 10.1038/tp.2016.133 PG 9 WC Psychiatry SC Psychiatry GA DW1RV UT WOS:000383421200004 PM 27483383 ER PT J AU Mormino, EC Sperling, RA Holmes, AJ Buckner, RL De Jager, PL Smoller, JW Sabuncu, MR AF Mormino, Elizabeth C. Sperling, Reisa A. Holmes, Avram J. Buckner, Randy L. De Jager, Philip L. Smoller, Jordan W. Sabuncu, Mert R. CA Alzheimer's Dis Neuroimaging Initi TI Polygenic risk of Alzheimer disease is associated with early- and late-life processes SO NEUROLOGY LA English DT Article ID PROGRESS; PLANS AB Objective: To examine associations between aggregate genetic risk and Alzheimer disease (AD) markers in stages preceding the clinical symptoms of dementia using data from 2 large observational cohort studies. Methods: We computed polygenic risk scores (PGRS) using summary statistics from the International Genomics of Alzheimer's Project genome-wide association study of AD. Associations between PGRS and AD markers (cognitive decline, clinical progression, hippocampus volume, and beta-amyloid) were assessed within older participants with dementia. Associations between PGRS and hippocampus volume were additionally examined within healthy younger participants (age 18-35 years). Results: Within participants without dementia, elevated PGRS was associated with worse memory (p = 0.002) and smaller hippocampus (p = 0.002) at baseline, as well as greater longitudinal cognitive decline (memory: p = 0.0005, executive function: p = 0.01) and clinical progression (p < 0.00001). HighPGRS was associated with AD-like levels of beta-amyloid burden as measured with florbetapir PET (p = 0.03) but did not reach statistical significance for CSF beta-amyloid (p = 0.11). Within the younger group, higher PGRS was associated with smaller hippocampus volume (p = 0.05). This pattern was evident when examining a PGRS that included many loci below the genome-wide association study (GWAS)-level significance threshold (16,123 single nucleotide polymorphisms), but not when PGRS was restricted to GWAS-level significant loci (18 single nucleotide polymorphisms). Conclusions: Effects related to common genetic risk loci distributed throughout the genome are detectable among individuals without dementia. The influence of this genetic risk may begin in early life and make an individual more susceptible to cognitive impairment in late life. Future refinement of polygenic risk scores may help identify individuals at risk for AD dementia. C1 [Mormino, Elizabeth C.; Sperling, Reisa A.] Harvard Med Sch, Dept Neurol, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Sperling, Reisa A.] Harvard Med Sch, Dept Radiol, Massachusetts Gen Hosp, Charlestown, MA USA. [Sperling, Reisa A.] Harvard Med Sch, Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Dept Neurol, Boston, MA USA. [De Jager, Philip L.] Harvard Med Sch, Brigham & Womens Hosp, Program Translat NeuroPsychiat Genom, Inst Neurosci,Dept Neurol, Boston, MA USA. [De Jager, Philip L.] Harvard Med Sch, Brigham & Womens Hosp, Program Translat NeuroPsychiat Genom, Inst Neurosci,Dept Psychiat, Boston, MA USA. [De Jager, Philip L.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA. [Holmes, Avram J.] Yale Univ, Dept Psychol, New Haven, CT USA. [Holmes, Avram J.] Harvard Med Sch, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA USA. [Holmes, Avram J.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Buckner, Randy L.] Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. [Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Buckner, Randy L.; Sabuncu, Mert R.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [De Jager, Philip L.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Smoller, Jordan W.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. RP Mormino, EC (reprint author), Harvard Med Sch, Dept Neurol, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. EM bmormino@nmr.mgh.harvard.edu FU NIH [F32AG044054, P01AG036694, K01MH099232, R01AG036836, K24MH094614, K25EB013649]; Alzheimer's Disease Neuroimaging Initiative (ADNI) (NIH) [U01 AG024904]; DOD ADNI (Department of Defense) [W81XWH-12-2-0012]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; AbbVie; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC; Johnson & Johnson Pharmaceutical Research & Development LLC; Lumosity; Lundbeck; Merck Co., Inc.; Meso Scale Diagnostics, LLC; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; Transition Therapeutics; Canadian Institutes of Health Research FX This work was funded by NIH grants F32AG044054 (E.C.M.), P01AG036694 (R.A.S.), K01MH099232 (A.J.H.), R01AG036836 (P.L.D.), K24MH094614 (J.W.S.), and K25EB013649 (M.R.S.). Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (NIH grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through contributions from the following: AbbVie; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC; Johnson & Johnson Pharmaceutical Research & Development LLC; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for NeuroImaging at the University of Southern California. The data from younger participants were collected as part of the Brain Genomics Superstruct Project (http://neuroinformatics.harvard.edu/gsp/). NR 23 TC 2 Z9 2 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD AUG 2 PY 2016 VL 87 IS 5 BP 481 EP 488 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA DU6LO UT WOS:000382326500012 PM 27385740 ER PT J AU Hirschtritt, ME Darrow, SM Illmann, C Osiecki, L Grados, M Sandor, P Dion, Y King, RA Pauls, DL Budman, CL Cath, DC Greenberg, E Lyon, GJ Yu, DM McGrath, LM McMahon, WM Lee, PC Delucchi, KL Scharf, JM Mathews, CA AF Hirschtritt, Matthew E. Darrow, Sabrina M. Illmann, Cornelia Osiecki, Lisa Grados, Marco Sandor, Paul Dion, Yves King, Robert A. Pauls, David L. Budman, Cathy L. Cath, Danielle C. Greenberg, Erica Lyon, Gholson J. Yu, Dongmei McGrath, Lauren M. McMahon, William M. Lee, Paul C. Delucchi, Kevin L. Scharf, Jeremiah M. Mathews, Carol A. CA TSAICG TI Social disinhibition is a heritable subphenotype of tics in Tourette syndrome SO NEUROLOGY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; SYMPTOM DIMENSIONS; COMPONENTS; NUMBER; MODEL; PAIR AB Objective: To identify heritable symptom-based subtypes of Tourette syndrome (TS). Methods: Forty-nine motor and phonic tics were examined in 3,494 individuals (1,191 TS probands and 2,303 first-degree relatives). Item-level exploratory factor and latent class analyses (LCA) were used to identify tic-based subtypes. Heritabilities of the subtypes were estimated, and associations with clinical characteristics were examined. Results: A 6-factor exploratory factor analysis model provided the best fit, which paralleled the somatotopic representation of the basal ganglia, distinguished simple from complex tics, and separated out socially disinhibited and compulsive tics. The 5-class LCA model best distinguished among the following groups: unaffected, simple tics, intermediate tics without social disinhibition, intermediate with social disinhibition, and high rates of all tic types. Across models, a phenotype characterized by high rates of social disinhibition emerged. This phenotype was associated with increased odds of comorbid psychiatric disorders, in particular, obsessive-compulsive disorder and attention-deficit/hyperactivity disorder, earlier age at TS onset, and increased tic severity. The heritability estimate for this phenotype based on the LCA was 0.53 (SE 0.08, p 1.7 X 10(-18)). Conclusions: Expanding on previous modeling approaches, a series of TS-related phenotypes, including one characterized by high rates of social disinhibition, were identified. These phenotypes were highly heritable and may reflect underlying biological networks more accurately than traditional diagnoses, thus potentially aiding future genetic, imaging, and treatment studies. C1 [Hirschtritt, Matthew E.; Darrow, Sabrina M.; Delucchi, Kevin L.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Illmann, Cornelia; Osiecki, Lisa; Pauls, David L.; Greenberg, Erica; Yu, Dongmei; Scharf, Jeremiah M.] Harvard Med Sch, Massachusetts Gen Hosp, Psychiat & Neurodevel Genet Unit, Ctr Human Genet Res,Dept Psychiat, Boston, MA USA. [Grados, Marco] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Sandor, Paul] Univ Toronto, Dept Psychiat, Toronto, ON M5S 1A1, Canada. Univ Hlth Network, Youthdale Treatment Ctr, Toronto, ON, Canada. [Dion, Yves] Univ Montreal, Dept Psychiat, Montreal, PQ H3C 3J7, Canada. [King, Robert A.] Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT USA. [Budman, Cathy L.] North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA. [Cath, Danielle C.] Univ Utrecht, Fac Social & Behav Sci, Utrecht, Netherlands. Altrecht Acad Anxiety Ctr, Utrecht, Netherlands. [Lyon, Gholson J.] Cold Spring Harbor Lab, Stanley Inst Cognit Genom, POB 100, Cold Spring Harbor, NY 11724 USA. [McGrath, Lauren M.] Amer Univ, Sch Educ, Washington, DC 20016 USA. [McMahon, William M.] Univ Utah, Dept Psychiat, Salt Lake City, UT USA. [Lee, Paul C.] Tripler Army Med Ctr, Dept Behav Hlth, Honolulu, HI 96859 USA. [Scharf, Jeremiah M.] Harvard Med Sch, Brigham & Womens Hosp, Div Cognit & Behav Neurol, Boston, MA USA. [Scharf, Jeremiah M.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. [Mathews, Carol A.] Univ Florida, Dept Psychiat, Gainesville, FL 32611 USA. RP Mathews, CA (reprint author), Univ Florida, Dept Psychiat, Gainesville, FL 32611 USA. EM carolmathews@ufl.edu FU NIH [R01MH096767, U01NS040024, K23MH085057, K02MH00508, R01NS016648]; Tourette Syndrome Association FX This work was supported by the NIH, grants R01MH096767 ("Refining the Tourette syndrome phenotype across diagnoses to aid gene discovery," principal investigator [PI]: Carol Mathews), U01NS040024 ("A genetic linkage study of GTS," PI: David Pauls/Jeremiah Scharf), K23MH085057 ("Translational phenomics and genomics of Gilles de la Tourette syndrome," PI: Jeremiah Scharf), K02MH00508 ("Genetics of a behavioral disorder: Tourette syndrome," PI: David Pauls), and R01NS016648 ("A genetic study of GTS, OCD, and ADHD," PI: David Pauls), and from the Tourette Syndrome Association. These funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. None of the funding agencies for this project (NINDS, NIMH, the Tourette Syndrome Association) had any influence or played any role in (1) the design or conduct of the study; (2) management, analysis, or interpretation of the data; (3) preparation, review, or approval of the manuscript. The views expressed in this publication are those of the authors and do not reflect the official policy or position of the Department of the Army, Department of Defense, or the US Government. NR 28 TC 4 Z9 4 U1 1 U2 1 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 AUG 2 PY 2016 VL 87 IS 5 BP 497 EP 504 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA DU6LO UT WOS:000382326500014 PM 27371487 ER PT J AU Jack, CR Bennett, DA Blennow, K Carrillo, MC Feldman, HH Frisoni, GB Hampel, H Jagust, WJ Johnson, KA Knopman, DS Petersen, RC Scheltens, P Sperling, RA Dubois, B AF Jack, Clifford R., Jr. Bennett, David A. Blennow, Kaj Carrillo, Maria C. Feldman, Howard H. Frisoni, Giovanni B. Hampel, Harald Jagust, William J. Johnson, Keith A. Knopman, David S. Petersen, Ronald C. Scheltens, Philip Sperling, Reisa A. Dubois, Bruno TI A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers SO NEUROLOGY LA English DT Review ID MILD COGNITIVE IMPAIRMENT; POSITRON-EMISSION-TOMOGRAPHY; PRIMARY PROGRESSIVE APHASIA; CREUTZFELDT-JAKOB-DISEASE; TRAUMATIC BRAIN-INJURY; PITTSBURGH COMPOUND-B; CSF TOTAL TAU; CEREBROSPINAL-FLUID; A-BETA; ASSOCIATION WORKGROUPS AB Biomarkers have become an essential component of Alzheimer disease (AD) research and because of the pervasiveness of AD pathology in the elderly, the same biomarkers are used in cognitive aging research. A number of current issues suggest that an unbiased descriptive classification scheme for these biomarkers would be useful. We propose the "A/T/N" system in which 7 major AD biomarkers are divided into 3 binary categories based on the nature of the pathophysiology that each measures. "A" refers to the value of a beta-amyloid biomarker (amyloid PET or CSF A beta(42)); "T," the value of a tau biomarker (CSF phospho tau, or tau PET); and "N," biomarkers of neurodegeneration or neuronal injury ([F-18]-fluorodeoxyglucose-PET, structural MRI, or CSF total tau). Each biomarker category is rated as positive or negative. An individual score might appear as A+/T+/N-, or A+/T+/N-, etc. The A/T/N system includes the new modality tau PET. It is agnostic to the temporal ordering of mechanisms underlying AD pathogenesis. It includes all individuals in any population regardless of the mix of biomarker findings and therefore is suited to population studies of cognitive aging. It does not specify disease labels and thus is not a diagnostic classification system. It is a descriptive system for categorizing multidomain biomarker findings at the individual person level in a format that is easy to understand and use. Given the present lack of consensus among AD specialists on terminology across the clinically normal to dementia spectrum, a biomarker classification scheme will have broadest acceptance if it is independent from any one clinically defined diagnostic scheme. C1 [Jack, Clifford R., Jr.] Mayo Clin, Dept Radiol, Rochester, MN USA. [Knopman, David S.; Petersen, Ronald C.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Blennow, Kaj] Univ Gothenburg, Molndal Hosp, Sahlgrenska Univ Hosp, Neurochem Lab,Dept Neurosci & Physiol, Molndal, Sweden. [Carrillo, Maria C.] Alzheimers Assoc, Chicago, IL USA. [Feldman, Howard H.] Univ British Columbia, Div Neurol, UBC Hosp Clin Alzheimers Dis & Related Disorders, Vancouver, BC, Canada. [Frisoni, Giovanni B.] Univ Hosp, Memory Clin, Geneva, Switzerland. Univ Geneva, Geneva, Switzerland. [Frisoni, Giovanni B.] Natl Ctr Alzheimers Dis, IRCCS Fatebenefratelli, Brescia, Italy. [Hampel, Harald] Univ Paris 06, Sorbonne Univ, Paris, France. Hop La Pitie Salpetriere, Inst Memoire & Malad Alzheimer IM2A, Paris, France. [Hampel, Harald] Hop La Pitie Salpetriere, Inst Cerveau & Moelleepiniere ICM, Dept Neurol, Paris, France. [Jagust, William J.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. [Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Scheltens, Philip] Vrije Univ Amsterdam, Alzheimer Ctr, Amsterdam, Netherlands. [Scheltens, Philip] Vrije Univ Amsterdam, Dept Neurol, Amsterdam, Netherlands. [Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. [Dubois, Bruno] Inst Cerveau & Moelle Epiniere, Ctr Malad Cognit & Comportementales, Paris, France. [Dubois, Bruno] Univ Paris 06, Hop Salpetriere, AP HP, Paris, France. RP Jack, CR (reprint author), Mayo Clin, Dept Radiol, Rochester, MN USA. EM jack.clifford@mayo.edu OI Feldman, Howard/0000-0002-9258-4538 FU NIA NIH HHS [P01 AG036694, K24 AG035007] NR 60 TC 9 Z9 9 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD AUG 2 PY 2016 VL 87 IS 5 BP 539 EP 547 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA DU6LO UT WOS:000382326500021 PM 27371494 ER PT J AU Gillis, WQ Kirmizitas, A Iwasaki, Y Ki, DH Wyrick, JM Thomsen, GH AF Gillis, William Q. Kirmizitas, Arif Iwasaki, Yasuno Ki, Dong-Hyuk Wyrick, Jonathan M. Thomsen, Gerald H. TI Gtpbp2 is a positive regulator of Wnt signaling and maintains low levels of the Wnt negative regulator Axin SO CELL COMMUNICATION AND SIGNALING LA English DT Article DE Axin; GTPase; Gtpbp2; Wnt signaling; Xenopus embryo ID BETA-CATENIN; XENOPUS EMBRYOS; PROTEIN STABILITY; PATHWAY; PHOSPHORYLATION; GASTRULATION; UBIQUITINATION; TRANSCRIPTION; DEGRADATION; INHIBITION AB Background: Canonical Wnt signals, transduced by stabilized beta-catenin, play similar roles across animals in maintaining stem cell pluripotency, regulating cell differentiation, and instructing normal embryonic development. Dysregulated Wnt/beta-catenin signaling causes diseases and birth defects, and a variety of regulatory processes control this pathway to ensure its proper function and integration with other signaling systems. We previously identified GTP-binding protein 2 (Gtpbp2) as a novel regulator of BMP signaling, however further exploration revealed that Gtpbp2 can also affect Wnt signaling, which is a novel finding reported here. Results: Knockdown of Gtpbp2 in Xenopus embryos causes severe axial defects and reduces expression of Spemann-Mangold organizer genes. Gtpbp2 knockdown blocks responses to ectopic Wnt8 ligand, such as organizer gene induction in ectodermal tissue explants and induction of secondary axes in whole embryos. However, organizer gene induction by ectopic Nodal2 is unaffected by Gtpbp2 knockdown. Epistasis tests, conducted by activating Wnt signal transduction at sequential points in the canonical pathway, demonstrate that Gtpbp2 is required downstream of Dishevelled and Gsk3 beta but upstream of beta-catenin, which is similar to the previously reported effects of Axin1 overexpression in Xenopus embryos. Focusing on Axin in Xenopus embryos, we find that knockdown of Gtpbp2 elevates endogenous or exogenous Axin protein levels. Furthermore, Gtpbp2 fusion proteins co-localize with Dishevelled and co-immunoprecipitate with Axin and Gsk3b. Conclusions: We conclude that Gtpbp2 is required for canonical Wnt/beta-catenin signaling in Xenopus embryos. Our data suggest a model in which Gtpbp2 suppresses the accumulation of Axin protein, a rate-limiting component of the beta-catenin destruction complex, such that Axin protein levels negatively correlate with Gtpbp2 levels. This model is supported by the similarity of our Gtpbp2-Wnt epistasis results and previously reported effects of Axin overexpression, the physical interactions of Gtpbp2 with Axin, and the correlation between elevated Axin protein levels and lost Wnt responsiveness upon Gtpbp2 knockdown. A wide variety of cancer-causing Wnt pathway mutations require low Axin levels, so development of Gtpbp2 inhibitors may provide a new therapeutic strategy to elevate Axin and suppress aberrant beta-catenin signaling in cancer and other Wnt-related diseases. C1 [Gillis, William Q.; Kirmizitas, Arif; Iwasaki, Yasuno; Ki, Dong-Hyuk; Wyrick, Jonathan M.; Thomsen, Gerald H.] SUNY Stony Brook, Ctr Dev Genet, Dept Biochem & Cell Biol, Grad Program Mol & Cellular Biol, Stony Brook, NY 11794 USA. [Gillis, William Q.] SUNY Coll Old Westbury, Dept Biol Sci, Old Westbury, NY 11568 USA. [Kirmizitas, Arif] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DS, England. [Ki, Dong-Hyuk] Harvard Med Sch, Childrens Hosp Boston, Dana Farber Canc Inst, Dept Pediat Oncol,Div Hematol Oncol, Boston, MA USA. RP Thomsen, GH (reprint author), SUNY Stony Brook, Ctr Dev Genet, Dept Biochem & Cell Biol, Grad Program Mol & Cellular Biol, Stony Brook, NY 11794 USA. EM gerald.h.thomsen@stonybrook.edu OI KIRMIZITAS, ARIF/0000-0001-6503-5974 FU NIH [5R01GM080462]; Carol Baldwin Foundation Award (Stony Brook TRO); NIDDK [5T32DK007521]; NIGMS [1K12GM102778] FX This work was supported by NIH grant 5R01GM080462, and a Carol Baldwin Foundation Award (Stony Brook TRO 2014) to GHT. Support for WQG was from NIDDK 5T32DK007521 and NIGMS 1K12GM102778. NR 49 TC 0 Z9 0 U1 3 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-811X J9 CELL COMMUN SIGNAL JI Cell Commun. Signal. PD AUG 2 PY 2016 VL 14 AR 15 DI 10.1186/s12964-016-0138-x PG 12 WC Cell Biology SC Cell Biology GA DT3MU UT WOS:000381386200001 PM 27484226 ER PT J AU Duan-Porter, W Goldstein, KM McDuffie, JR Hughes, JM Clowse, MEB Klap, RS Masilamani, V LaPointe, NMA Nagi, A Gierisch, JM Williams, JW AF Duan-Porter, Wei Goldstein, Karen M. McDuffie, Jennifer R. Hughes, Jaime M. Clowse, Megan E. B. Klap, Ruth S. Masilamani, Varsha LaPointe, Nancy M. Allen Nagi, Avishek Gierisch, Jennifer M. Williams, John W., Jr. TI Reporting of Sex Effects by Systematic Reviews on Interventions for Depression, Diabetes, and Chronic Pain SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID RANDOMIZED-CONTROLLED-TRIAL; LOW-BACK-PAIN; ACUTE MYOCARDIAL-INFARCTION; CARDIOVASCULAR RISK-FACTORS; SELF-MANAGEMENT EDUCATION; INDIVIDUAL PATIENT DATA; LOW-GLYCEMIC-INDEX; QUALITY-OF-LIFE; CLINICAL-TRIALS; KNEE OSTEOARTHRITIS AB Systematic reviews (SRs) have the potential to contribute uniquely to the evaluation of sex and gender differences (termed "sex effects"). This article describes the reporting of sex effects by SRs on interventions for depression, type 2 diabetes mellitus, and chronic pain conditions (chronic low back pain, knee osteoarthritis, and fibromyalgia). It includes SRs published since 1 October 2009 that evaluate medications, behavioral interventions, exercise, quality improvement, and some condition-specific treatments. The reporting of sex effects by primary randomized, controlled trials is also examined. Of 313 eligible SRs (86 for depression, 159 for type 2 diabetes mellitus, and 68 for chronic pain), few (n = 29) reported sex effects. Most SRs reporting sex effects used metaregression, whereas 9 SRs used subgroup analysis or individual-patient data meta-analysis. The proportion of SRs reporting the sex distribution of primary studies varied from a low of 31% (n = 8) for low back pain to a high of 68% (n = 23) for fibromyalgia. Primary randomized, controlled trials also infrequently reported sex effects, and most lacked an adequate sample size to examine them. Therefore, all SRs should report the proportion of women enrolled in primary studies and evaluate sex effects using appropriate methods whenever power is adequate. C1 Durham Vet Affairs Med Ctr, Durham, NC USA. [Clowse, Megan E. B.] Duke Univ, Sch Med, 200 Trent Dr,7 Baker House, Durham, NC 27710 USA. [Hughes, Jaime M.] Univ N Carolina, Campus Box 7200, Chapel Hill, NC 27599 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Durham Vet Affairs Med Ctr, Hlth Adm Hlth Serv Res & Dev, 411 West Chapel Hill St,Suite 600, Durham, NC 27701 USA. [Duan-Porter, Wei; McDuffie, Jennifer R.; Masilamani, Varsha; Nagi, Avishek] Durham Vet Affairs Med Ctr, Hlth Serv Res & Dev, 411 West Chapel Hill St,Suite 600, Durham, NC 27701 USA. [Goldstein, Karen M.; Gierisch, Jennifer M.] Durham Vet Affairs Med Ctr, Hlth Serv Res & Dev, 508 Fulton St, Durham, NC 27705 USA. [Klap, Ruth S.] Vet Affairs West Los Angeles Med Ctr, 11301 Wilshire Blvd,Bldg 206,Room 231, Los Angeles, CA 90073 USA. [LaPointe, Nancy M. Allen] Duke Univ, Med Ctr, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. [Williams, John W., Jr.] Durham Vet Affairs Med Ctr, Hlth Serv Res & Dev, 411 West Chapel Hill St,Suite 500, Durham, NC 27701 USA. RP Duan-Porter, W (reprint author), Durham Vet Affairs Med Ctr, Hlth Adm Hlth Serv Res & Dev, 411 West Chapel Hill St,Suite 600, Durham, NC 27701 USA. EM wei.duan-porter@duke.edu FU Veterans Affairs Office of Academic Affiliations [TPM 21-022]; Veterans Health Administration Health Services Research Development [13-263] FX By the Veterans Affairs Office of Academic Affiliations (fellowship support TPM 21-022; Dr. Duan-Porter) and the Veterans Health Administration Health Services Research & Development (Career Development Award 13-263; Dr. Goldstein). NR 122 TC 0 Z9 0 U1 6 U2 8 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 2 PY 2016 VL 165 IS 3 BP 184 EP + DI 10.7326/M15-2877 PG 21 WC Medicine, General & Internal SC General & Internal Medicine GA DS2HA UT WOS:000380583300007 PM 27111355 ER PT J AU Barkoudah, E Weinrauch, LA AF Barkoudah, Ebrahim Weinrauch, Larry A. TI Screening for Abnormal Blood Glucose and Type 2 Diabetes Mellitus SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 [Barkoudah, Ebrahim; Weinrauch, Larry A.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Barkoudah, Ebrahim] Harvard Med Sch, Boston, MA USA. [Weinrauch, Larry A.] EP Joslin Res Lab, Boston, MA USA. RP Barkoudah, E (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 2 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 2 PY 2016 VL 165 IS 3 BP 225 EP 225 DI 10.7326/L16-0100 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA DS2HA UT WOS:000380583300013 PM 27479224 ER PT J AU Cain, KD Sehgal, BR Covinsky, KE Kaelber, DC Sehgal, AR AF Cain, Katrice D. Sehgal, Bindu R. Covinsky, Kenneth E. Kaelber, David C. Sehgal, Ashwini R. TI The Clinical Impact of Medical Journals SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 [Cain, Katrice D.; Sehgal, Ashwini R.] Case Western Reserve Univ, Metrohlth Med Ctr, Ctr Reducing Hlth Dispar, Cleveland, OH 44106 USA. [Sehgal, Bindu R.] Premier Phys Ctr, Westlake, OH USA. [Covinsky, Kenneth E.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Kaelber, David C.] Case Western Reserve Univ, Metrohlth Med Ctr, Ctr Clin Informat Res & Educ, Cleveland, OH USA. RP Cain, KD (reprint author), Case Western Reserve Univ, Metrohlth Med Ctr, Ctr Reducing Hlth Dispar, Cleveland, OH 44106 USA. NR 4 TC 1 Z9 1 U1 1 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 2 PY 2016 VL 165 IS 3 BP 227 EP 228 DI 10.7326/M16-1096 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA DS2HA UT WOS:000380583300016 PM 27294687 ER PT J AU McMillan, BJ Tibbe, C Jeon, H Drabek, AA Klein, T Blacklow, SC AF McMillan, Brian J. Tibbe, Christine Jeon, Hyesung Drabek, Andrew A. Klein, Thomas Blacklow, Stephen C. TI Electrostatic Interactions between Elongated Monomers Drive Filamentation of Drosophila Shrub, a Metazoan ESCRT-III Protein SO Cell Reports LA English DT Article ID STRUCTURAL BASIS; MEMBRANE DEFORMATION; COMPLEX; CYTOKINESIS; PATHWAY; HELICES; SYSTEM AB The endosomal sorting complex required for transport (ESCRT) is a conserved protein complex that facilitates budding and fission of membranes. It executes a key step in many cellular events, including cytokinesis and multi-vesicular body formation. The ESCRT-III protein Shrub in flies, or its homologs in yeast (Snf7) or humans (CHMP4B), is a critical polymerizing component of ESCRT-III needed to effect membrane fission. We report the structural basis for polymerization of Shrub and define a minimal region required for filament formation. The X-ray structure of the Shrub core shows that individual monomers in the lattice interact in a staggered arrangement using complementary electrostatic surfaces. Mutations that disrupt interface salt bridges interfere with Shrub polymerization and function. Despite substantial sequence divergence and differences in packing interactions, the arrangement of Shrub subunits in the polymer resembles that of Snf7 and other family homologs, suggesting that this intermolecular packing mechanism is shared among ESCRT-III proteins. C1 [McMillan, Brian J.; Drabek, Andrew A.; Blacklow, Stephen C.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Tibbe, Christine; Klein, Thomas] Univ Dusseldorf, D-40225 Dusseldorf, Germany. [Jeon, Hyesung; Blacklow, Stephen C.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. RP Blacklow, SC (reprint author), Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.; Blacklow, SC (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. EM stephen_blacklow@hms.harvard.edu FU NIH [CA092433, CA119070]; Deutsche Forschungsgemeinschaft (DFG) [SFB 1208] FX This work was supported in part by NIH awards CA092433 and CA119070, project 3 (to S.C.B.), and by the Deutsche Forschungsgemeinschaft (DFG) through SFB 1208, project B01 (to T.K.). NR 26 TC 1 Z9 1 U1 0 U2 1 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 AUG 2 PY 2016 VL 16 IS 5 BP 1211 EP 1217 DI 10.1016/j.celrep.2016.06.093 PG 7 WC Cell Biology SC Cell Biology GA DS4KE UT WOS:000380749200003 PM 27452459 ER PT J AU Stratton, MS Lin, CY Anand, P Tatman, PD Ferguson, BS Wickers, ST Ambardekar, AV Sucharov, CC Bradner, JE Haldar, SM McKinsey, TA AF Stratton, Matthew S. Lin, Charles Y. Anand, Priti Tatman, Philip D. Ferguson, Bradley S. Wickers, Sean T. Ambardekar, Amrut V. Sucharov, Carmen C. Bradner, James E. Haldar, Saptarsi M. McKinsey, Timothy A. TI Signal-Dependent Recruitment of BRD4 to Cardiomyocyte Super-Enhancers Is Suppressed by a MicroRNA SO Cell Reports LA English DT Article ID BROMODOMAIN PROTEIN BRD4; PULMONARY ARTERIAL-HYPERTENSION; RIGHT-VENTRICULAR HYPERTROPHY; HEART-FAILURE; CELL IDENTITY; P-TEFB; TRANSCRIPTIONAL ELONGATION; DILATED CARDIOMYOPATHY; SELECTIVE-INHIBITION; CARDIAC-HYPERTROPHY AB BRD4 governs pathological cardiac gene expression by binding acetylated chromatin, resulting in enhanced RNA polymerase II (Pol II) phosphorylation and transcription elongation. Here, we describe a signal-dependent mechanism for the regulation of BRD4 in cardiomyocytes. BRD4 expression is suppressed by microRNA-9 (miR-9), which targets the 3' UTR of the Brd4 transcript. In response to stress stimuli, miR-9 is downregulated, leading to derepression of BRD4 and enrichment of BRD4 at long-range super-enhancers (SEs) associated with pathological cardiac genes. A miR-9 mimic represses stimulus-dependent targeting of BRD4 to SEs and blunts Pol II phosphorylation at proximal transcription start sites, without affecting BRD4 binding to SEs that control constitutively expressed cardiac genes. These findings suggest that dynamic enrichment of BRD4 at SEs genome-wide serves a crucial role in the control of stress-induced cardiac gene expression and define a miR-dependent signaling mechanism for the regulation of chromatin state and Pol II phosphorylation. C1 [Stratton, Matthew S.; Tatman, Philip D.; Ferguson, Bradley S.; Wickers, Sean T.; Ambardekar, Amrut V.; Sucharov, Carmen C.; McKinsey, Timothy A.] Univ Colorado Denver, Div Cardiol, Dept Med, Aurora, CO 80045 USA. [Lin, Charles Y.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Anand, Priti; Haldar, Saptarsi M.] Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA. [Tatman, Philip D.; McKinsey, Timothy A.] Univ Colorado Denver, Med Scientist Training Program, Aurora, CO 80045 USA. [Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Haldar, Saptarsi M.] UCSF Sch Med, Div Cardiol, Dept Med, San Francisco, CA 94143 USA. [Haldar, Saptarsi M.] UCSF Sch Med, Cardiovasc Res Inst, San Francisco, CA 94143 USA. RP McKinsey, TA (reprint author), Univ Colorado Denver, Div Cardiol, Dept Med, Aurora, CO 80045 USA.; McKinsey, TA (reprint author), Univ Colorado Denver, Med Scientist Training Program, Aurora, CO 80045 USA. EM timothy.mckinsey@ucdenver.edu FU NIH [R01HL127240, R01HL116848, R21AG043822, DK093821]; American Heart Association [14510001]; T32 training grant; F32 fellowship from NIH [5T32HL007822, F32HL126354]; US Department of Defense CDMRP [CA120184]; Scientist Development Grant (from American Heart Association); Boettcher Foundation's Webb-Waring Biomedical Research Program; NIH/NCATS Colorado CTSA grant [UL1 TR001082] FX We thank miRagen Therapeutics for the control mimic, members of the K. Song lab for assistance with microscopy, and C. Vinson (NCI) for Ad-dnAP-1/AFos. This work was supported by NIH R01HL127240 (to J.E.B., S.M.H., and T.A.M.). T.A.M. was also supported by the NIH (R01HL116848 and R21AG043822) and the American Heart Association (Grant-in-Aid 14510001). S.M.H. was also supported by NIH DK093821. M.S.S. was funded by a T32 training grant and an F32 fellowship from the NIH (5T32HL007822 and F32HL126354). C.Y.L. is supported by a US Department of Defense CDMRP CA120184 postdoctoral fellowship. A.V.A. is supported by a Scientist Development Grant (from the American Heart Association) and the Boettcher Foundation's Webb-Waring Biomedical Research Program. The REDCap database used in the maintenance of the human cardiac tissue bank was supported by NIH/NCATS Colorado CTSA grant UL1 TR001082. NR 46 TC 0 Z9 0 U1 7 U2 7 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 AUG 2 PY 2016 VL 16 IS 5 BP 1366 EP 1378 DI 10.1016/j.celrep.2016.06.074 PG 13 WC Cell Biology SC Cell Biology GA DS4KE UT WOS:000380749200017 PM 27425608 ER PT J AU Heydari, B Abdullah, S Pottala, JV Shah, R Abbasi, S Mandry, D Francis, SA Lumish, H Ghoshhajra, BB Hoffmann, U Appelbaum, E Feng, JZH Blankstein, R Steigner, M McConnell, JP Harris, W Antman, EM Jerosch-Herold, M Kwong, RY AF Heydari, Bobak Abdullah, Shuaib Pottala, James V. Shah, Ravi Abbasi, Siddique Mandry, Damien Francis, Sanjeev A. Lumish, Heidi Ghoshhajra, Brian B. Hoffmann, Udo Appelbaum, Evan Feng, Jiazhuo H. Blankstein, Ron Steigner, Michael McConnell, Joseph P. Harris, William Antman, Elliott M. Jerosch-Herold, Michael Kwong, Raymond Y. TI Effect of Omega-3 Acid Ethyl Esters on Left Ventricular Remodeling After Acute Myocardial Infarction The OMEGA-REMODEL Randomized Clinical Trial SO CIRCULATION LA English DT Article DE endomyocardial fibrosis; fatty acids, omega-3; infarction; magnetic resonance imaging; ventricular remodeling ID EXTRACELLULAR-MATRIX EXPANSION; AMERICAN-HEART-ASSOCIATION; HEALTH-CARE PROFESSIONALS; ADIPONECTIN SECRETION; FATTY-ACIDS; DISEASE; DYSFUNCTION; OMEGA-3-FATTY-ACIDS; QUANTIFICATION; CARVEDILOL AB BACKGROUND: Omega-3 fatty acids from fish oil have been associated with beneficial cardiovascular effects, but their role in modifying cardiac structures and tissue characteristics in patients who have had an acute myocardial infarction while receiving current guideline-based therapy remains unknown. METHODS: In a multicenter, double-blind, placebo-controlled trial, participants presenting with an acute myocardial infarction were randomly assigned 1: 1 to 6 months of high-dose omega-3 fatty acids (n= 180) or placebo (n= 178). Cardiac magnetic resonance imaging was used to assess cardiac structure and tissue characteristics at baseline and after study therapy. The primary study endpoint was change in left ventricular systolic volume index. Secondary endpoints included change in noninfarct myocardial fibrosis, left ventricular ejection fraction, and infarct size. RESULTS: By intention-to-treat analysis, patients randomly assigned to omega-3 fatty acids experienced a significant reduction of left ventricular systolic volume index (-5.8%, P= 0.017), and noninfarct myocardial fibrosis (-5.6%, P= 0.026) in comparison with placebo. Per-protocol analysis revealed that those patients who achieved the highest quartile increase in red blood cell omega-3 index experienced a 13% reduction in left ventricular systolic volume index in comparison with the lowest quartile. In addition, patients in the omega-3 fatty acid arm underwent significant reductions in serum biomarkers of systemic and vascular inflammation and myocardial fibrosis. There were no adverse events associated with highdose omega-3 fatty acid therapy. CONCLUSIONS: Treatment of patients with acute myocardial infarction with high-dose omega-3 fatty acids was associated with reduction of adverse left ventricular remodeling, noninfarct myocardial fibrosis, and serum biomarkers of systemic inflammation beyond current guidelinebased standard of care. C1 [Heydari, Bobak; Abdullah, Shuaib; Shah, Ravi; Abbasi, Siddique; Mandry, Damien; Feng, Jiazhuo H.; Blankstein, Ron; Steigner, Michael; Jerosch-Herold, Michael; Kwong, Raymond Y.] Brigham & Womens Hosp, Dept Med, Cardiovasc Div, Noninvas Cardiovasc Imaging Sect, 75 Francis St, Boston, MA 02115 USA. [Heydari, Bobak; Abdullah, Shuaib; Shah, Ravi; Abbasi, Siddique; Mandry, Damien; Feng, Jiazhuo H.; Blankstein, Ron; Steigner, Michael; Jerosch-Herold, Michael; Kwong, Raymond Y.] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. [Heydari, Bobak; Abdullah, Shuaib; Shah, Ravi; Abbasi, Siddique; Mandry, Damien; Feng, Jiazhuo H.; Antman, Elliott M.; Kwong, Raymond Y.] Brigham & Womens Hosp, Dept Med, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA. [Pottala, James V.; Harris, William] Univ South Dakota, Sanford Sch Med, Dept Internal Med, Sioux Falls, SD USA. [Shah, Ravi; Francis, Sanjeev A.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Lumish, Heidi; Ghoshhajra, Brian B.; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Appelbaum, Evan] Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Boston, MA 02215 USA. [McConnell, Joseph P.] Hlth Diagnost Lab Inc, Richmond, VA USA. [Harris, William] OmegaQuant Analyt LLC, Sioux Falls, SD USA. RP Kwong, RY (reprint author), Brigham & Womens Hosp, Dept Med, Cardiovasc Div, Cardiac Magnet Resonance Imaging, 75 Francis St, Boston, MA 02115 USA.; Kwong, RY (reprint author), Harvard Med Sch, Med, 75 Francis St, Boston, MA 02115 USA. EM rykwong@partners.org FU National Heart, Lung, and Blood Institute of the National Institutes of Health FX The National Heart, Lung, and Blood Institute of the National Institutes of Health funded this study. NR 37 TC 7 Z9 7 U1 5 U2 7 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 AUG 2 PY 2016 VL 134 IS 5 BP 378 EP + DI 10.1161/CIRCULATIONAHA.115.019949 PG 17 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DS2NB UT WOS:000380612600007 PM 27482002 ER PT J AU Kirtane, AJ Doshi, D Leon, MB Lasala, JM Ohman, EM O'Neill, WW Shroff, A Cohen, MG Palacios, IF Beohar, N Uriel, N Kapur, NK Karmpaliotis, D Lombardi, W Dangas, GD Parikh, MA Stone, GW Moses, JW AF Kirtane, Ajay J. Doshi, Darshan Leon, Martin B. Lasala, John M. Ohman, E. Magnus O'Neill, William W. Shroff, Adhir Cohen, Mauricio G. Palacios, Igor F. Beohar, Nirat Uriel, Nir Kapur, Navin K. Karmpaliotis, Dimitri Lombardi, William Dangas, George D. Parikh, Manish A. Stone, Gregg W. Moses, Jeffrey W. TI Treatment of Higher-Risk Patients With an Indication for Revascularization Evolution Within the Field of Contemporary Percutaneous Coronary Intervention SO CIRCULATION LA English DT Article DE angioplasty; coronary artery disease; coronary occlusion; heart failure; percutaneous coronary intervention ID QUALITY-OF-LIFE; ELEVATION MYOCARDIAL-INFARCTION; ASSOCIATION TASK-FORCE; ARTERY-BYPASS SURGERY; CARDIOVASCULAR DATA REGISTRY; AMERICAN-HEART-ASSOCIATION; APPROPRIATE USE CRITERIA; CHRONIC TOTAL OCCLUSIONS; THORACIC-SURGEONS; UNITED-STATES AB Patients with severe coronary artery disease with a clinical indication for revascularization but who are at high procedural risk because of patient comorbidities, complexity of coronary anatomy, and/or poor hemodynamics represent an understudied and potentially underserved patient population. Through advances in percutaneous interventional techniques and technologies and improvements in patient selection, current percutaneous coronary intervention may allow appropriate patients to benefit safely from revascularization procedures that might not have been offered in the past. The burgeoning interest in these procedures in some respects reflects an evolutionary step within the field of percutaneous coronary intervention. However, because of the clinical complexity of many of these patients and procedures, it is critical to develop dedicated specialists within interventional cardiology who are trained with the cognitive and technical skills to select these patients appropriately and to perform these procedures safely. Preprocedural issues such as multidisciplinary risk and treatment assessments are highly relevant to the successful treatment of these patients, and knowledge gaps and future directions to improve outcomes in this emerging area are discussed. Ultimately, an evolution of contemporary interventional cardiology is necessary to treat the increasingly higher-risk patients with whom we are confronted. C1 [Kirtane, Ajay J.; Doshi, Darshan; Leon, Martin B.; Karmpaliotis, Dimitri; Parikh, Manish A.; Stone, Gregg W.; Moses, Jeffrey W.] Columbia Univ, Med Ctr, New York Presbyterian Hosp, Herbert & Sandi Feinberg Intervent Cardiol & Hear, New York, NY USA. [Kirtane, Ajay J.; Doshi, Darshan; Leon, Martin B.; Karmpaliotis, Dimitri; Parikh, Manish A.; Stone, Gregg W.; Moses, Jeffrey W.] Cardiovasc Res Fdn, New York, NY USA. [Lasala, John M.] Washington Univ, St Louis, MO USA. [Ohman, E. Magnus] Duke Univ, Med Ctr, Program Adv Coronary Dis, Durham, NC USA. [O'Neill, William W.] Henry Ford Hosp, Detroit, MI USA. [Shroff, Adhir] Univ Illinois, Chicago, IL USA. [Cohen, Mauricio G.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Palacios, Igor F.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Beohar, Nirat] Mt Sinai Med Ctr, Miami, FL USA. [Uriel, Nir] Univ Chicago, Chicago, IL 60637 USA. [Kapur, Navin K.] Tufts Med Ctr, Boston, MA USA. [Lombardi, William] Univ Washington, Med Ctr, Seattle, WA 98195 USA. [Dangas, George D.] Mt Sinai Med Ctr, New York, NY 10029 USA. RP Kirtane, AJ (reprint author), 161 Ft Washington Ave,6th Floor, New York, NY 10032 USA. EM akirtane@columbia.edu FU Boston Scientific; Medtronic; Abbott Vascular; Abiomed; St. Jude Medical; Eli Lilly; Abiomed Inc.; Daiichi Sankyo; Gilead Sciences; Daiichi-Sankyo/Eli Lilly and Co; AstraZeneca; Boehringer Ingelheim; Bristol-Myers Squibb; Janssen Pharmaceuticals; Liposcience; Medicines Company; Merck/Schering Plow; Pozen; Roche; Sanofi-Aventis; WebMD; Thoratec; Heartware; Cardiac Assist; Maquet; Bristol-Myers Squibb/Sanofi; Eli Lilly and Co/Daiichi-Sankyo; Covidien; Regado Biosciences; Maya Medical; Merck Co FX Dr Kirtane reports institutional research grants to Columbia University from Boston Scientific, Medtronic, Abbott Vascular, Abiomed, St. Jude Medical, and Eli Lilly. Dr Doshi reports an educational grant from Abiomed Inc. Dr Karmpaliotis reports serving on the speakers' bureau for Abbott Vascular, Boston Scientific, Medtronic, and Asahi. Dr Leon reports serving on the advisory board for Boston Scientific and Medtronic. Dr. Lasala reports speaker fees from Abiomed, St. Jude Medical, Eli Lilly, Boston Scientific, and Daiichi Sankyo; serving on the advisory board for Abiomed and Boston Scientific; and being a stockholder in Abiomed. Dr Ohman has received grant support from Gilead Sciences and Daiichi-Sankyo/Eli Lilly and Co, as well as consultant fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Liposcience, The Medicines Company, Merck/Schering Plow, Pozen, Roche, Sanofi-Aventis, and WebMD. Dr Shroff has been a consultant for Medtronic, Abiomed, Terumo Medical, and The Medicines Company. Dr Cohen has been on the speakers' bureau for Medtronic; has been a consultant for AstraZeneca, Abiomed, Daiichi Sankyo, and Terumo Medical; and has received research support from Boston Scientific and Abbott Vascular. Dr Uriel has been a consultant for Thoratec, Heartware, Abiomed, and Medtronic and has received grant support from Thoratec and Heartware. Dr Kapur reports serving on the speakers' bureau for Abiomed, Maquet, and Heartware; being a consultant for Abiomed, Cardiac Assist, Maquet, and Thoratec; and receiving research support from Abiomed, Cardiac Assist, and Maquet. Dr Dangas reports institutional research grant support from The Medicines Company, Bristol-Myers Squibb/Sanofi, and Eli Lilly and Co/Daiichi-Sankyo, as well as consulting fees from Abbott Vascular, AstraZeneca, Boston Scientific, Covidien, Janssen Pharmaceuticals, Regado Biosciences, Maya Medical, Merck & Co, and The Medicines Company. Dr Lombardi has served as a consultant to Abbott Vascular, Boston Scientific, and Abiomed; has been on the advisory board for Abbott Vascular and Boston Scientific; is an employee (spouse) of Spectranetics; and holds equity in Bridgepoint Medical Systems. Dr Parikh reports serving on the speakers' bureau for Abbott Vascular, Medtronic, CSI, and Boston Scientific and on the advisory board for Abbott Vascular, Medtronic, and Philips. Dr Moses reports consultant fees from Boston Scientific and Abiomed. The remaining authors report no conflicts. NR 47 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD AUG 2 PY 2016 VL 134 IS 5 BP 422 EP + DI 10.1161/CIRCULATIONAHA.116.022061 PG 17 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DS2NB UT WOS:000380612600010 PM 27482004 ER PT J AU Kousoulis, AA Ioakeim-Ioannidou, M Economopoulos, KP AF Kousoulis, Antonis A. Ioakeim-Ioannidou, Myrsini Economopoulos, Konstantinos P. TI Access to health for refugees in Greece: lessons in inequalities SO International Journal for Equity in Health LA English DT Article DE Access; Conflict; Greece; Inequality; Migrants; Refugee; Syria ID INTERVENTIONS AB Eastern Greek islands have been direct passageways of (mainly Syrian) refugees to the European continent over the past year. However, basic medical care has been insufficient. Despite calls for reform, the Greek healthcare system has for many years been costly and dysfunctional, lacking universal equity of access. Thus, mainly volunteers look after the refugee camps in the Greek islands under adverse conditions. Communicable diseases, trauma related injuries and mental health problems are the most common issues facing the refugees. The rapid changes in the epidemiology of multiple conditions that are seen in countries with high immigration rates, like Greece, demand pragmatic solutions. Best available knowledge should be used in delivering health interventions. So far, Greece is failed by international aid, and cross-border policies have not effectively tackled underlying reasons for ill-health in this context, like poverty, conflict and equity of access. C1 [Kousoulis, Antonis A.; Ioakeim-Ioannidou, Myrsini; Economopoulos, Konstantinos P.] Soc Jr Doctors, Athens, Greece. [Kousoulis, Antonis A.] London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, 10 Norwood Ave, London HA0 1LY, England. [Ioakeim-Ioannidou, Myrsini] Univ Athens, Sch Med, Athens, Greece. [Economopoulos, Konstantinos P.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. RP Kousoulis, AA (reprint author), Soc Jr Doctors, Athens, Greece.; Kousoulis, AA (reprint author), London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, 10 Norwood Ave, London HA0 1LY, England. EM antonis.kousoulis@lshtm.ac.uk FU Society of Junior Doctors FX The Society of Junior Doctors funded expenses for deployment of members to Lesbos. None other source for the study. NR 7 TC 1 Z9 1 U1 19 U2 30 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-9276 J9 INT J EQUITY HEALTH JI Int. J. Equity Health PD AUG 2 PY 2016 VL 15 AR 122 DI 10.1186/s12939-016-0409-6 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DS3DM UT WOS:000380663200001 PM 27485633 ER PT J AU Lee, VS Halabi, CM Hoffman, EP Carmichael, N Leshchiner, I Lian, CG Bierhals, AJ Vuzman, D Mecham, RP Frank, NY Stitziel, NO AF Lee, Vivian S. Halabi, Carmen M. Hoffman, Erin P. Carmichael, Nikkola Leshchiner, Ignaty Lian, Christine G. Bierhals, Andrew J. Vuzman, Dana Mecham, Robert P. Frank, Natasha Y. Stitziel, Nathan O. CA Brigham Genomic Med TI Loss of function mutation in LOX causes thoracic aortic aneurysm and dissection in humans SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE whole-genome sequencing; CRISPR/Cas9; aortic dissection; genetics; lysyl oxidase ID LYSYL-OXIDASE; MARFAN-SYNDROME; CROSS-LINKING; MOUSE; MICE; EXPRESSION; ELASTIN; BETA; HAPLOINSUFFICIENCY; ELASTOGENESIS AB Thoracic aortic aneurysms and dissections (TAAD) represent a substantial cause of morbidity and mortality worldwide. Many individuals presenting with an inherited form of TAAD do not have causal mutations in the set of genes known to underlie disease. Using whole-genome sequencing in two first cousins with TAAD, we identified a missense mutation in the lysyl oxidase (LOX) gene (c.893T > G encoding p.Met298Arg) that cosegregated with disease in the family. Using clustered regularly interspaced short palindromic repeats (CRISPR)/clustered regularly interspaced short palindromic repeats-associated protein-9 nuclease (Cas9) genome engineering tools, we introduced the human mutation into the homologous position in the mouse genome, creating mice that were heterozygous and homozygous for the human allele. Mutant mice that were heterozygous for the human allele displayed disorganized ultrastructural properties of the aortic wall characterized by fragmented elastic lamellae, whereas mice homozygous for the human allele died shortly after parturition from ascending aortic aneurysm and spontaneous hemorrhage. These data suggest that a missense mutation in LOX is associated with aortic disease in humans, likely through insufficient cross-linking of elastin and collagen in the aortic wall. Mutation carriers may be predisposed to vascular diseases because of weakened vessel walls under stress conditions. LOX sequencing for clinical TAAD may identify additional mutation carriers in the future. Additional studies using our mouse model of LOX-associated TAAD have the potential to clarify the mechanism of disease and identify novel therapeutics specific to this genetic cause. C1 [Lee, Vivian S.; Halabi, Carmen M.; Mecham, Robert P.] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. [Halabi, Carmen M.] Washington Univ, Sch Med, Dept Pediat, Div Nephrol, St Louis, MO 63110 USA. [Hoffman, Erin P.; Carmichael, Nikkola; Leshchiner, Ignaty; Vuzman, Dana; Frank, Natasha Y.] Brigham & Womens Hosp, Div Genet, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Carmichael, Nikkola; Leshchiner, Ignaty; Lian, Christine G.; Vuzman, Dana; Frank, Natasha Y.] Harvard Med Sch, Boston, MA 02115 USA. [Lian, Christine G.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Bierhals, Andrew J.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. [Frank, Natasha Y.] VA Boston Healthcare Syst, Boston, MA 02132 USA. [Stitziel, Nathan O.] Washington Univ, Sch Med, Dept Med, Div Cardiovasc, St Louis, MO 63110 USA. [Stitziel, Nathan O.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [Stitziel, Nathan O.] Washington Univ, Sch Med, McDonnell Genome Inst, St Louis, MO 63110 USA. [Hoffman, Erin P.] Littleton Adventist Hosp, Dept Oncol, Littleton, CO 80122 USA. RP Frank, NY (reprint author), Brigham & Womens Hosp, Div Genet, Dept Med, 75 Francis St, Boston, MA 02115 USA.; Frank, NY (reprint author), Harvard Med Sch, Boston, MA 02115 USA.; Frank, NY (reprint author), VA Boston Healthcare Syst, Boston, MA 02132 USA.; Stitziel, NO (reprint author), Washington Univ, Sch Med, Dept Med, Div Cardiovasc, St Louis, MO 63110 USA.; Stitziel, NO (reprint author), Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.; Stitziel, NO (reprint author), Washington Univ, Sch Med, McDonnell Genome Inst, St Louis, MO 63110 USA. EM nfrank@partners.org; nstitziel@wustl.edu FU Hope Center Transgenic Vectors Core and Mouse Genetics Core at the Washington University School of Medicine; National Heart, Lung, and Blood Institute [R01HL105314, R01HL53325, K08HL114642, R01HL131961, T32HL125241]; National Institute of Biomedical Imaging and Bioengineering Training Grant [T32EB18266]; Foundation for Barnes-Jewish Hospital FX We thank the family presented here for participating in this study. We also thank Russell Knutsen and Marilyn Levy for the mouse physiology and EM studies, respectively; and Phillip Trackman (Boston University) for assistance with the LOX activity assay. This work was supported, in part, by the Hope Center Transgenic Vectors Core and Mouse Genetics Core at the Washington University School of Medicine. Funds supporting this work were provided by National Heart, Lung, and Blood Institute Grants R01HL105314 (to R.P.M.), R01HL53325 (to R.P.M.), K08HL114642 (to N.O.S.), and R01HL131961 (to N.O.S.). V.S.L. was supported by National Institute of Biomedical Imaging and Bioengineering Training Grant T32EB18266 and National Heart, Lung, and Blood Institute Training Grant T32HL125241. C.M.H. is a Scholar of the Child Health Research Center at Washington University School of Medicine (K12-HD076224). R.P.M. and N.O.S. are also supported, in part, by The Foundation for Barnes-Jewish Hospital. NR 47 TC 2 Z9 2 U1 3 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 2 PY 2016 VL 113 IS 31 BP 8759 EP 8764 DI 10.1073/pnas.1601442113 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DS2HH UT WOS:000380586600061 PM 27432961 ER PT J AU Kahle, KT Flores, B Bharucha-Goebel, D Zhang, JW Donkervoort, S Hegde, M Hussain, G Duran, D Liang, B Sun, DD Bonnemann, CG Delpire, E AF Kahle, Kristopher T. Flores, Bianca Bharucha-Goebel, Diana Zhang, Jinwei Donkervoort, Sandra Hegde, Madhuri Hussain, Gulnaz Duran, Daniel Liang, Bo Sun, Dandan Bonnemann, Carsten G. Delpire, Eric TI Peripheral motor neuropathy is associated with defective kinase regulation of the KCC3 cotransporter SO Science Signaling LA English DT Article ID CATION-CHLORIDE COTRANSPORTERS; CONDITIONAL MOUSE MODEL; CELL-VOLUME HOMEOSTASIS; K+-CL-COTRANSPORTER; CORPUS-CALLOSUM; MISSENSE MUTATIONS; ANDERMANN-SYNDROME; HEREDITARY MOTOR; DISEASE; MICE AB Using exome sequencing, we identified a de novo mutation (c.2971A>G; T991A) in SLC12A6, the gene encoding the K+-Cl(-)cotransporter KCC3, in a patient with an early-onset, progressive, and severe peripheral neuropathy primarily affecting motor neurons. Normally, the WNK kinase-dependent phosphorylation of T-991 tonically inhibits KCC3; however, cell swelling triggers Thr(991) dephosphorylation to activate the transporter and restore cell volume. KCC3 (T991A) mutation in patient cells abolished Thr(991) phosphorylation, resulted in constitutive KCC3 activity, and compromised cell volume homeostasis. KCC3(T991A/T991A) mutant mice exhibited constitutive KCC3 activity and recapitulated aspects of the clinical, electrophysiological, and histopathological findings of the patient. These results suggest that the function of the peripheral nervous system depends on finely tuned, kinase-regulated KCC3 activity and implicate abnormal cell volume homeostasis as a previously unreported mechanism of axonal degeneration. C1 [Kahle, Kristopher T.; Zhang, Jinwei; Duran, Daniel] Yale Sch Med, Ctr Mendelian Genom, Dept Neurosurg, New Haven, CT 06510 USA. [Kahle, Kristopher T.; Zhang, Jinwei; Duran, Daniel] Yale Sch Med, Ctr Mendelian Genom, Dept Pediat & Cellular & Mol Physiol, New Haven, CT 06510 USA. [Flores, Bianca; Delpire, Eric] Vanderbilt Univ, Sch Med, Dept Anesthesiol, Nashville, TN 37232 USA. [Bharucha-Goebel, Diana; Donkervoort, Sandra; Bonnemann, Carsten G.] NINDS, Neuromuscular & Neurogenet Disorders Childhood Se, Neurogenet Branch, Bethesda, MD 20814 USA. [Bharucha-Goebel, Diana] Childrens Natl Hlth Syst, Dept Neurol, Washington, DC 20010 USA. [Zhang, Jinwei] Univ Dundee, Coll Life Sci, Prot Phosphorylat & Ubiquitylat Unit, MRC, Dundee DD15EH, Scotland. [Hegde, Madhuri] Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA. [Hussain, Gulnaz; Sun, Dandan] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. [Hussain, Gulnaz; Sun, Dandan] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res, Educ & Clin Ctr, Pittsburgh, PA 15240 USA. [Liang, Bo] Harvard Med Sch, Dept MicroBiol, Boston, MA 02114 USA. [Liang, Bo] Harvard Med Sch, Dept Immunobiol, Boston, MA 02114 USA. RP Delpire, E (reprint author), Vanderbilt Univ, Sch Med, Dept Anesthesiol, Nashville, TN 37232 USA.; Bonnemann, CG (reprint author), NINDS, Neuromuscular & Neurogenet Disorders Childhood Se, Neurogenet Branch, Bethesda, MD 20814 USA. EM carsten.bonnemann@nih.gov; eric.delpire@vanderbilt.edu OI Duran, Daniel/0000-0001-6888-252X; Zhang, Jinwei/0000-0001-8683-509X FU NIH [GM74771, 2T32MH064913-11A1, T32-AR056993]; Harvard-Massachusetts Institute of Technology Neuroscience Grant; Manton Center for Orphan Disease Research at Harvard Medical School; March of Dimes Basil O'Connor Award; NINDS FX This work was supported by NIH research grant GM74771 (E.D.). K.T.K. was supported by a Harvard-Massachusetts Institute of Technology Neuroscience Grant, the Manton Center for Orphan Disease Research at Harvard Medical School, and the March of Dimes Basil O'Connor Award. C.G.B. is supported by intramural funds of the NINDS. B.F. and D.B.G. received support from NIH grants 2T32MH064913-11A1 and T32-AR056993, respectively. NR 51 TC 2 Z9 2 U1 1 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1945-0877 EI 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD AUG 2 PY 2016 VL 9 IS 439 AR ra77 DI 10.1126/scisignal.aae0546 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DS4VJ UT WOS:000380779400001 PM 27485015 ER PT J AU Paganetti, H Yu, CX Orton, CG AF Paganetti, Harald Yu, Cedric X. Orton, Colin G. TI Photon radiotherapy has reached its limit in terms of catching up dosimetrically with proton therapy SO MEDICAL PHYSICS LA English DT Editorial Material ID BODY RADIATION-THERAPY; DELIVERY C1 [Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Paganetti, Harald] Harvard Med Sch, Boston, MA 02114 USA. [Yu, Cedric X.] Univ Maryland, Sch Med, Dept Radiat Oncol, Baltimore, MD 21201 USA. RP Paganetti, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.; Paganetti, H (reprint author), Harvard Med Sch, Boston, MA 02114 USA. EM hpaganetti@mgh.harvard.edu; yu002@umaryland.edu NR 12 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 EI 2473-4209 J9 MED PHYS JI Med. Phys. PD AUG PY 2016 VL 43 IS 8 BP 4470 EP 4472 DI 10.1118/1.4954790 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EN2UW UT WOS:000395866800002 PM 27487862 ER PT J AU Andreasen, D Van Leemput, K Edmund, JM AF Andreasen, Daniel Van Leemput, Koen Edmund, Jens M. TI A patch-based pseudo-CT approach for MRI-only radiotherapy in the pelvis SO MEDICAL PHYSICS LA English DT Article DE radiotherapy; MRI-only; pseudo-CT; patch; pelvis ID ULTRASHORT ECHO TIME; MAGNETIC-RESONANCE; ATTENUATION CORRECTION; COMPUTED-TOMOGRAPHY; RADIATION-THERAPY; ELECTRON-DENSITY; BRAIN; SEQUENCES; PROSTATE; PET/MRI AB Purpose: In radiotherapy based only on magnetic resonance imaging (MRI), knowledge about tissue electron densities must be derived from the MRI. This can be achieved by converting the MRI scan to the so-called pseudo-computed tomography (pCT). An obstacle is that the voxel intensities in conventional MRI scans are not uniquely related to electron density. The authors previously demonstrated that a patch-based method could produce accurate pCTs of the brain using conventional Ti-weighted MRI scans. The method was driven mainly by local patch similarities and relied on simple affine registrations between an atlas database of the co-registered MRI/CT scan pairs and the MRI scan to be converted. In this study, the authors investigate the applicability of the patch-based approach in the pelvis. This region is challenging for a method based on local similarities due to the greater inter-patient variation. The authors benchmark the method against a baseline pCT strategy where all voxels inside the body contour are assigned a water-equivalent bulk density. Furthermore, the authors implement a parallelized approximate patch search strategy to speed up the pCT generation time to a more clinically relevant level. Methods: The data consisted of CT and T-1-weighted MRI scans of 10 prostate patients. pCTs were generated using an approximate patch search algorithm in a leave-one-out fashion and compared with the CT using frequently described metrics such as the voxel-wise mean absolute error (MAE(VOX)) and the deviation in water-equivalent path lengths. Furthermore, the dosimetric accuracy was tested for a volumetric modulated arc therapy plan using dose volume histogram (DVH) point deviations and gamma-index analysis. Results: The patch-based approach had an average MAE,x of 54 HU; median deviations of less than 0.4% in relevant DVH points and a gamma-index pass rate of 0.97 using a 1%/1 mm criterion. The patch-based approach showed a significantly better performance than the baseline water pCT in almost all metrics. The approximate patch search strategy was 70x faster than a brute-force search, with an average prediction time of 20.8 min. Conclusions: The authors showed that a patch-based method based on affine registrations and T-1-weighted MRI could generate accurate pCTs of the pelvis. The main source of differences between pCT and CT was positional changes of air pockets and body outline. (C) 2016 American Association of Physicists in Medicine. C1 [Andreasen, Daniel; Van Leemput, Koen] Tech Univ Denmark, Dept Appl Math & Comp Sci, DK-2800 Lyngby, Denmark. [Andreasen, Daniel; Edmund, Jens M.] Univ Copenhagen, Gentofte & Herlev Hosp, Dept Oncol, Radiotherapy Res Unit, DK-2730 Herlev, Denmark. [Van Leemput, Koen] Harvard Med Sch, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Andreasen, D (reprint author), Tech Univ Denmark, Dept Appl Math & Comp Sci, DK-2800 Lyngby, Denmark.; Andreasen, D (reprint author), Univ Copenhagen, Gentofte & Herlev Hosp, Dept Oncol, Radiotherapy Res Unit, DK-2730 Herlev, Denmark. EM dana@dtu.dk FU Varian Medical Systems, Inc. FX This work was supported by a research grant from Varian Medical Systems, Inc. NR 44 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 EI 2473-4209 J9 MED PHYS JI Med. Phys. PD AUG PY 2016 VL 43 IS 8 BP 4742 EP 4752 DI 10.1118/1.4958676 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EN2UW UT WOS:000395866800032 PM 27487892 ER PT J AU Andreyev, A Celler, A Ozsahin, I Sitek, A AF Andreyev, A. Celler, A. Ozsahin, I. Sitek, A. TI Resolution recovery for Compton camera using origin ensemble algorithm SO MEDICAL PHYSICS LA English DT Article DE Compton camera; resolution recovery; origin ensemble; image reconstruction ID IMAGE-RECONSTRUCTION; GAMMA-CAMERA; SPATIAL-RESOLUTION; EMISSION; TOMOGRAPHY; SCATTERING; PET AB Purpose: Compton cameras (CCs) use electronic collimation to reconstruct the images of activity distribution. Although this approach can greatly improve imaging efficiency, due to complex geometry of the CC principle, image reconstruction with the standard iterative algorithms, such as ordered subset expectation maximization (OSEM), can be very time-consuming, even more so if resolution recovery (RR) is implemented. We have previously shown that the origin ensemble (OE) algorithm can be used for the reconstruction of the CC data. Here we propose a method of extending our OE algorithm to include RR. Methods: To validate the proposed algorithm we used Monte Carlo simulations of a CC composed of multiple layers of pixelated CZT detectors and designed for imaging small animals. A series of CC acquisitions of small hot spheres and the Derenzo phantom placed in air were simulated. Images obtained from (a) the exact data, (b) blurred data but reconstructed without resolution recovery, and (c) blurred and reconstructed with resolution recovery were compared. Furthermore, the reconstructed contrast-to-background ratios were investigated using the phantom with nine spheres placed in a hot background. Results: Our simulations demonstrate that the proposed method allows for the recovery of the resolution loss that is due to imperfect accuracy of event detection. Additionally, tests of camera sensitivity corresponding to different detector configurations demonstrate that the proposed CC design has sensitivity comparable to PET. When the same number of events were considered, the computation time per iteration increased only by a factor of 2 when OE reconstruction with the resolution recovery correction was performed relative to the original OE algorithm. We estimate that the addition of resolution recovery to the OSEM would increase reconstruction times by 2-3 orders of magnitude per iteration. Conclusions: The results of our tests demonstrate the improvement of image resolution provided by the OE reconstructions with resolution recovery. The quality of images and their contrast are similar to those obtained from the OE reconstructions from scans simulated with perfect energy and spatial resolutions. (C) 2016 American Association of Physicists in Medicine. C1 [Andreyev, A.] Philips Healthcare, Highland Hts, OH 44143 USA. [Andreyev, A.; Celler, A.] Univ British Columbia, Med Imaging Res Grp, Vancouver, BC V5Z 1M9, Canada. [Andreyev, A.; Celler, A.] Vancouver Coastal Hlth Res Inst, Vancouver, BC V5Z 1M9, Canada. [Ozsahin, I.; Sitek, A.] Massachusetts Gen Hosp, Gordon Ctr Med Imaging, Boston, MA 02114 USA. [Ozsahin, I.; Sitek, A.] Harvard Med Sch, Dept Radiol, Boston, MA 02115 USA. [Sitek, A.] Brigham & Womens Hosp, Boston, MA 02114 USA. [Sitek, A.] Harvard Med Sch, Boston, MA 02114 USA. [Sitek, A.] Philips Res, Cambridge, MA 02141 USA. RP Sitek, A (reprint author), Massachusetts Gen Hosp, Gordon Ctr Med Imaging, Boston, MA 02114 USA.; Sitek, A (reprint author), Harvard Med Sch, Dept Radiol, Boston, MA 02115 USA.; Sitek, A (reprint author), Philips Res, Cambridge, MA 02141 USA. EM sarkadiu@gmail.com FU NIH [R21HL-106474, R21EB016315]; Canadian Institute of Health Research (CIHR) Institute of Genetics [NHG-91363]; TUBITAK [2219] FX This work was supported in part by NIH Nos. R21HL-106474 and R21EB016315, by the Canadian Institute of Health Research (CIHR) Institute of Genetics (Catalyst Grant No. NHG-91363), and by TUBITAK 2219 award. NR 19 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 EI 2473-4209 J9 MED PHYS JI Med. Phys. PD AUG PY 2016 VL 43 IS 8 BP 4866 EP 4876 DI 10.1118/1.4959551 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EN2UW UT WOS:000395866800044 PM 27487904 ER PT J AU Toltz, A Hoesl, M Schuemann, J Seuntjens, J Lu, HM Paganetti, H AF Toltz, Allison Hoesl, Michaela Schuemann, Jan Seuntjens, Jan Lu, Hsiao-Ming Paganetti, Harald TI Time-resolved diode dosimetry for in vivo proton therapy range verification: calibration through numerical modeling SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Canadian-Organization-of-Medical-Physicists CY JUL 20-23, 2016 CL St Johns, CANADA SP Canadian Org Med Physicists C1 McGill Univ, Montreal, PQ H3A 2T5, Canada. Harvard Univ, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 EI 2473-4209 J9 MED PHYS JI Med. Phys. PD AUG PY 2016 VL 43 IS 8 MA 16 BP 4939 EP 4939 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EN2UW UT WOS:000395866800089 ER PT J AU Collins-Fekete, CA Beaulieu, L Seco, J AF Collins-Fekete, Charles-Antoine Beaulieu, Luc Seco, Joao TI On the use of proton radiography to reduce beam range uncertainties and improve patient positioning accuracy in proton therapy SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Canadian-Organization-of-Medical-Physicists CY JUL 20-23, 2016 CL St Johns, CANADA SP Canadian Org Med Physicists C1 Univ Laval, CHU Quebec, Quebec City, PQ, Canada. Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 EI 2473-4209 J9 MED PHYS JI Med. Phys. PD AUG PY 2016 VL 43 IS 8 MA 01 BP 4955 EP 4955 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EN2UW UT WOS:000395866800143 ER PT J AU Pyxaras, SA Hunziker, L Chieffo, A Meliga, E Latib, A Park, SJ Onuma, Y Capranzano, P Valgimigli, M Narbute, I Makkar, RR Palacios, IF Kim, YH Buszman, PP Chakravarty, T Sheiban, I Mehran, R Margey, R Agnihotri, A Marra, S Capodanno, D Leon, MB Moses, JW Fajadet, J Lefevre, T Morice, MC Erglis, A Tamburino, C Alfieri, O Serruys, PW Colombo, A Naber, CK AF Pyxaras, Stylianos A. Hunziker, Lukas Chieffo, Alaide Meliga, Emanuele Latib, Azeem Park, Seung-Jung Onuma, Yoshinobu Capranzano, Piera Valgimigli, Marco Narbute, Inga Makkar, Raj R. Palacios, Igor F. Kim, Young-Hak Buszman, Piotr P. Chakravarty, Tarun Sheiban, Imad Mehran, Roxana Margey, Ronan Agnihotri, Arvind Marra, Sebastiano Capodanno, Davide Leon, Martin B. Moses, Jeffrey W. Fajadet, Jean Lefevre, Thierry Morice, Marie-Claude Erglis, Andrejs Tamburino, Corrado Alfieri, Ottavio Serruys, Patrick W. Colombo, Antonio Naber, Christoph K. TI Long-term clinical outcomes after percutaneous coronary intervention versus coronary artery bypass grafting for acute coronary syndrome from the DELTA registry: a multicentre registry evaluating percutaneous coronary intervention versus coronary artery bypass grafting for left main treatment SO EUROINTERVENTION LA English DT Article DE acute coronary syndrome; coronary artery bypass grafting (CABG); outcome; percutaneous coronary intervention (PCI); unprotected left main ID DRUG-ELUTING STENTS; BARE-METAL STENTS; FOLLOW-UP; REVASCULARIZATION REGISTRY; SYNTAX SCORE; DISEASE; TRIAL; SURGERY; LESIONS; ANGIOPLASTY AB Aims: Our aim was to compare, in a large unprotected left main coronary artery (ULMCA) all-comer registry, the long-term clinical outcome after percutaneous coronary intervention (PCI) with first-generation drug-eluting stents (DES) versus coronary artery bypass grafting (CABG) in patients with acute coronary syndrome (ACS). Methods and results: Of a total of 2,775 patients enrolled in the Drug Eluting Stents for Left Main Coronary Artery Disease (DELTA) multicentre registry, 379 (13.7%) patients with ACS treated with PCI (n= 272) or CABG (n= 107) were analysed. Baseline demographics were considerably different in the two groups before propensity matching. No significant differences emerged for the composite endpoint of all-cause death, myocardial infarction (MI), and cerebrovascular accident (HR 1.11, 95% CI: 0.63-1.94; p= 0.727), all-cause death (HR 1.26, 95% CI: 0.68-2.32; p= 0.462), the composite endpoint of all-cause death and MI (HR 1.02, 95% CI: 0.56-1.84; p= 0.956), and major adverse cardiac and cerebrovascular events (HR 0.82, 95% CI: 0.50-1.36; p= 0.821). However, a higher incidence of target vessel revascularisation (HR 4.67, 95% CI: 1.33-16.47; p= 0.008) was observed in the PCI compared with the CABG group, which was confirmed in the propensity score-matched analysis. Conclusions: In the DELTA all-comer, multinational registry, PCI for ACS in ULMCA is associated with comparable clinical outcomes to those observed with CABG at long-term follow-up, despite the use of first-generation DES. C1 [Pyxaras, Stylianos A.; Hunziker, Lukas; Naber, Christoph K.] Elisabeth Krankenhaus Essen, Contilia Heart & Vasc Ctr, Klara Kopp Weg 1, D-45138 Essen, Germany. [Chieffo, Alaide; Latib, Azeem; Alfieri, Ottavio; Colombo, Antonio] Ist Sci San Raffaele, Dept Cardiothorac & Vasc Dis, Milan, Italy. [Meliga, Emanuele] AO Ordine Mauriziano Umberto I, Intervent Cardiol Unit, Turin, Italy. [Park, Seung-Jung; Kim, Young-Hak] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Cardiol,Ctr Med Res & Informat, Seoul, South Korea. [Onuma, Yoshinobu; Valgimigli, Marco; Serruys, Patrick W.] Erasmus MC, Thoraxctr, Rotterdam, Netherlands. [Capranzano, Piera; Capodanno, Davide; Tamburino, Corrado] Univ Catania, Ferrarotto Hosp, Cardiovasc Dept, Catania, Italy. [Narbute, Inga; Erglis, Andrejs] Pauls Stradins Clin Univ Hosp, Latvian Ctr Cardiol, Riga, Latvia. [Narbute, Inga; Erglis, Andrejs] Univ Latvia, Inst Cardiol, Riga, Latvia. [Makkar, Raj R.; Chakravarty, Tarun] Cedars Sinai Med Ctr, Cedars Sinai Heart Inst, Los Angeles, CA 90048 USA. [Palacios, Igor F.; Margey, Ronan; Agnihotri, Arvind] Massachusetts Gen Hosp, Cardiac Catheterizat Lab, Boston, MA 02114 USA. [Palacios, Igor F.; Margey, Ronan; Agnihotri, Arvind] Harvard Med Sch, Boston, MA USA. [Buszman, Piotr P.] Amer Heart Poland Inc, Katowice, Poland. [Sheiban, Imad; Marra, Sebastiano] Univ Turin, S Giovanni Battista Molinette Hosp, Div Cardiol, Intervent Cardiol, Turin, Italy. [Mehran, Roxana] Mt Sinai Med Ctr, New York, NY 10029 USA. [Leon, Martin B.; Moses, Jeffrey W.] Columbia Univ, Med Ctr, New York, NY USA. [Leon, Martin B.; Moses, Jeffrey W.] Cardiovasc Res Fdn, New York, NY USA. [Fajadet, Jean] Clin Pasteur, Toulouse, France. [Lefevre, Thierry; Morice, Marie-Claude] ICPS, Gen Sante, Massy, France. RP Pyxaras, SA (reprint author), Elisabeth Krankenhaus Essen, Contilia Heart & Vasc Ctr, Klara Kopp Weg 1, D-45138 Essen, Germany. EM steliospyxaras@gmail.com FU Lilly; Medtronic; Bristol-Myers Squibb/Sanofi, The Medicines Company; Lilly/Daiichi Sankyo; Abbott Vascular; Biotronik; Sadra Medical; Stentys; Icon FX D. Capodanno has received speaker's honoraria from Eli Lilly and AstraZeneca. R. Makkar is a consultant to Medtronic and Abiomed, has received speaker's fees from Lilly and Medtronic, and has received equity from Entourage Medical Technologies. R. Mehran is a consultant to Abbott Vascular, The Medicines Company, Janssen, and Regado, and has received research grant support from Bristol-Myers Squibb/Sanofi, The Medicines Company, and Lilly/Daiichi Sankyo. C. Naber is a speaker for Abbott Vascular, Cordis, Biotronik, Biosensors, Cirdus, Medtronic, Stentys, Daiichi Sankyo, and The Medicines Company, has received research support from Abbott Vascular, Biotronik, Sadra Medical, Stentys, and Icon, and is on the advisory board of Biotronik and Abbott Vascular. J. Moses is a consultant to Cordis and Boston Scientific. The other authors have no conflicts of interest to declare. The Guest Editor has no conflicts of interest to declare. NR 21 TC 3 Z9 3 U1 0 U2 0 PU EUROPA EDITION PI TOULOUSE CEDEX 6 PA 19 ALLEES JEAN JAURES B P 61508, TOULOUSE CEDEX 6, 31015, FRANCE SN 1774-024X EI 1969-6213 J9 EUROINTERVENTION JI EuroIntervention PD AUG PY 2016 VL 12 IS 5 BP E623 EP E631 DI 10.4244/EIJV12I5A102 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA EK6MX UT WOS:000394039800014 PM 27497362 ER PT J AU Young, JS Chen, J Miller, ML Vu, V Tian, C Moon, JJ Alegre, ML Sciammas, R Chong, AS AF Young, J. S. Chen, J. Miller, M. L. Vu, V. Tian, C. Moon, J. J. Alegre, M. -L. Sciammas, R. Chong, A. S. TI Delayed Cytotoxic T Lymphocyte-Associated Protein 4-Immunoglobulin Treatment Reverses Ongoing Alloantibody Responses and Rescues Allografts From Acute Rejection SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE basic (laboratory) research; science; immunosuppression; immune modulation; organ transplantation in general; immunobiology; alloantibody; animal models: murine; B cell biology; immunosuppressant; fusion proteins and monoclonal antibodies: belatacept; immunosuppressive regimens; rescue ID ANTIBODY-MEDIATED REJECTION; DONOR-SPECIFIC ANTIBODIES; FOLLICULAR HELPER-CELLS; INDOLEAMINE 2,3-DIOXYGENASE; KIDNEY-TRANSPLANTATION; DENDRITIC CELLS; GRAFT-SURVIVAL; COSTIMULATORY BLOCKADE; RENAL-TRANSPLANTATION; HEART-TRANSPLANTATION AB Antibody-mediated rejection has emerged as the leading cause of late graft loss in kidney transplant recipients, and inhibition of donor-specific antibody production should lead to improved transplant outcomes. The fusion protein cytotoxic T lymphocyte-associated protein 4-immunoglobulin (CTLA4-Ig) blocks T cell activation and consequently inhibits T-dependent B cell antibody production, and the current paradigm is that CTLA4-Ig is effective with naive T cells and less so with activated or memory T cells. In this study, we used a mouse model of allosensitization to investigate the efficacy of continuous CTLA4-Ig treatment, initiated 7 or 14 days after sensitization, for inhibiting ongoing allospecific B cell responses. Delayed treatment with CTLA4-Ig collapsed the allospecific germinal center B cell response and inhibited alloantibody production. Using adoptively transferred T cell receptor transgenic T cells and a novel approach to track endogenous graft-specific T cells, we demonstrate that delayed CTLA4-Ig minimally inhibited graft-specific CD4(+) and T follicular helper responses. Remarkably, delaying CTLA4-Ig until day 6 after transplantation in a fully mismatched heart transplant model inhibited alloantibody production and prevented acute rejection, whereas transferred hyperimmune sera reversed the effects of delayed CTLA4-Ig. Collectively, our studies revealed the unexpected efficacy of CTLA4-Ig for inhibiting ongoing B cell responses even when the graft-specific T cell response was robustly established. Young et al report on the unexpected efficacy of CTLA4-Ig at halting ongoing B cell responses even when treatment is initiated after the graft-specific T cell response is robustly established. C1 [Young, J. S.; Chen, J.; Vu, V.; Tian, C.; Sciammas, R.; Chong, A. S.] Univ Chicago, Dept Surg, Sect Transplantat, 5841 S Maryland Ave, Chicago, IL 60637 USA. [Miller, M. L.; Alegre, M. -L.] Univ Chicago, Dept Med, Rheumatol Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA. [Moon, J. J.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Moon, J. J.] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA. [Moon, J. J.] Harvard Med Sch, Boston, MA USA. [Sciammas, R.] Houston Methodist Hosp, Res Inst, Ctr Immunobiol & Transplant Res, Dept Surg, Houston, TX USA. RP Chong, AS (reprint author), Univ Chicago, Dept Surg, Sect Transplantat, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM achong@uchicago.edu FU National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) [1R01AI110513, P01AI097113]; American Heart Association (AHA) [15POST25700452]; Respiratory Biology Training Grant [T32 HL07605]; Cardiovascular Pathophysiology and Biochemistry Training Grant [T32 HL07237]; HHMI Med-into-Grad Program training grant [56006772]; AHA [13PRE14550022, 15PRE22180007]; NIH Tetramer Core Facility [HHSN272201300006C] FX We are grateful to Dr. Wink Baldwin, Cleveland Clinic, for his generous assistance in developing the C4d immunohistochemistry and to Ms. Rachel C Young for her artistic contributions. This work was supported in part by grants (1R01AI110513, P01AI097113) from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH). J.Y. received an American Heart Association (AHA) postdoctoral fellowship award and was funded by a Respiratory Biology Training Grant (T32 HL07605). J.S.Y. received an AHA postdoctoral fellowship award (15POST25700452) and was funded by a Respiratory Biology Training Grant (T32 HL07605). M.L.M. was funded by the Cardiovascular Pathophysiology and Biochemistry Training Grant (T32 HL07237), an HHMI Med-into-Grad Program training grant (56006772) and two AHA predoctoral fellowships (13PRE14550022 and 15PRE22180007). MHC class I tetramers were provided by the NIH Tetramer Core Facility (contract HHSN272201300006C). NR 59 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD AUG PY 2016 VL 16 IS 8 BP 2312 EP 2323 DI 10.1111/ajt.13761 PG 12 WC Surgery; Transplantation SC Surgery; Transplantation GA DR6QR UT WOS:000380026900012 ER PT J AU Sacher, AG Paweletz, C Dahlberg, SE Alden, RS O'Connell, A Feeney, N Mach, SL Janne, PA Oxnard, GR AF Sacher, Adrian G. Paweletz, Cloud Dahlberg, Suzanne E. Alden, Ryan S. O'Connell, Allison Feeney, Nora Mach, Stacy L. Jaenne, Pasi A. Oxnard, Geoffrey R. TI Prospective Validation of Rapid Plasma Genotyping for the Detection of EGFR and KRAS Mutations in Advanced Lung Cancer SO JAMA ONCOLOGY LA English DT Article ID SMALL-CELL-LUNG; FACTOR RECEPTOR MUTATION; CIRCULATING TUMOR DNA; DROPLET DIGITAL PCR; ACQUIRED-RESISTANCE; GEFITINIB; THERAPY; CHEMOTHERAPY; SURVIVAL; AZD9291 AB IMPORTANCE Plasma genotyping of cell-free DNA has the potential to allow for rapid noninvasive genotyping while avoiding the inherent shortcomings of tissue genotyping and repeat biopsies. OBJECTIVE To prospectively validate plasma droplet digital PCR (ddPCR) for the rapid detection of common epidermal growth factor receptor (EGFR) and KRAS mutations, as well as the EGFR T790M acquired resistance mutation. DESIGN, SETTING, AND PARTICIPANTS Patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) who either (1) had a new diagnosis and were planned for initial therapy or (2) had developed acquired resistance to an EGFR kinase inhibitor and were planned for rebiopsy underwent initial blood sampling and immediate plasma ddPCR for EGFR exon 19 del, L858R, T790M, and/or KRAS G12X between July 3, 2014, and June 30, 2015, at a National Cancer Institute-designated comprehensive cancer center. All patients underwent biopsy for tissue genotyping, which was used as the reference standard for comparison; rebiopsy was required for patients with acquired resistance to EGFR kinase inhibitors. Test turnaround time (TAT) was measured in business days from blood sampling until test reporting. MAIN OUTCOMES AND MEASURES Plasma ddPCR assay sensitivity, specificity, and TAT. RESULTS Of 180 patients with advanced NSCLC (62% female; median [range] age, 62 [37-93] years), 120 cases were newly diagnosed; 60 had acquired resistance. Tumor genotype included 80 EGFR exon 19/L858R mutants, 35 EGFR T790M, and 25 KRAS G12X mutants. Median (range) TAT for plasma ddPCR was 3 (1-7) days. Tissue genotyping median (range) TAT was 12 (1-54) days for patients with newly diagnosed NSCLC and 27 (1-146) days for patients with acquired resistance. Plasma ddPCR exhibited a positive predictive value of 100% (95% CI, 91%-100%) for EGFR 19 del, 100% (95% CI, 85%-100%) for L858R, and 100% (95% CI, 79%-100%) for KRAS, but lower for T790M at 79% (95% CI, 62%-91%). The sensitivity of plasma ddPCR was 82%(95% CI, 69%-91%) for EGFR 19 del, 74%(95% CI, 55%-88%) for L858R, and 77%(95% CI, 60%-90%) for T790M, but lower for KRAS at 64%(95% CI, 43%-82%). Sensitivity for EGFR or KRAS was higher in patients with multiple metastatic sites and those with hepatic or bone metastases, specifically. CONCLUSIONS AND RELEVANCE Plasma ddPCR detected EGFR and KRAS mutations rapidly with the high specificity needed to select therapy and avoid repeat biopsies. This assay may also detect EGFR T790M missed by tissue genotyping due to tumor heterogeneity in resistant disease. C1 [Sacher, Adrian G.; Alden, Ryan S.; Mach, Stacy L.; Jaenne, Pasi A.; Oxnard, Geoffrey R.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 450 Brookline Ave, Boston, MA 02215 USA. [Sacher, Adrian G.; Jaenne, Pasi A.; Oxnard, Geoffrey R.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Sacher, Adrian G.; Jaenne, Pasi A.; Oxnard, Geoffrey R.] Harvard Med Sch, Boston, MA USA. [Paweletz, Cloud; O'Connell, Allison; Feeney, Nora; Jaenne, Pasi A.] Dana Farber Canc Inst, Belfer Ctr Appl Canc Sci, Boston, MA 02115 USA. [Dahlberg, Suzanne E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dahlberg, Suzanne E.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA. RP Sacher, AG; Oxnard, GR (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM ags2185@cumc.columbia.edu; geoffrey_oxnard@dfci.harvard.edu FU US Department of Defense; National Cancer Institute of the National Institutes of Health [R01CA135257, R01CA114465, P50CA090578]; Phi Beta Psi Sorority; Stading-Younger Cancer Foundation; International Association for the Study of Lung Cancer; Canadian Institutes of Health Research; Canadian Association of Medical Oncologists; Kaplan Research Fund FX This research was supported in part by the US Department of Defense, the National Cancer Institute of the National Institutes of Health (grants R01CA135257, R01CA114465, and P50CA090578), the Phi Beta Psi Sorority, the Stading-Younger Cancer Foundation, the International Association for the Study of Lung Cancer, the Canadian Institutes of Health Research, the Canadian Association of Medical Oncologists, and the Kaplan Research Fund. NR 28 TC 27 Z9 29 U1 3 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD AUG PY 2016 VL 2 IS 8 BP 1014 EP 1022 DI 10.1001/jamaoncol.2016.0173 PG 9 WC Oncology SC Oncology GA DW5RN UT WOS:000383704700010 PM 27055085 ER PT J AU Singh, JA Yu, SH AF Singh, Jasvinder A. Yu, Shaohua TI Time Trends, Predictors, and Outcome of Emergency Department Use for Gout: A Nationwide US Study SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE GOUT; EMERGENCY ROOM; CHARGES; HOSPITALIZATION; INPATIENT USE; HEALTHCARE USE ID HEALTH-CARE UTILIZATION; HOSPITAL ADMISSIONS; GENERAL-POPULATION; TREATMENT PATTERNS; UNITED-STATES; ARTHRITIS; HYPERURICEMIA; COMORBIDITIES; COSTS AB Objective. To assess gout-related emergency department (ED) use/charges and discharge disposition. Methods. We used the US National ED Sample (NEDS) data to examine the time trends in total ED visits and charges and ED-related hospitalizations with gout as the primary diagnosis. We assessed multivariable-adjusted predictors of ED charges and hospitalization for gout-related visits using the 2012 NEDS data. Results. There were 180,789, 201,044, and 205,152 ED visits in 2009, 2010, and 2012 with gout as the primary diagnosis, with total ED charges of $195 million, $239 million, and $287 million, respectively; these accounted for 0.14%-0.16% of all ED visits. Mean/median 2012 ED charges/visit were $1398/$956. Of all gout-related ED visits, 7.7% were admitted to the hospital in 2012. Mean/median length of hospital stay was 3.9/2.6 days and mean/median inpatient charge/admission with gout as the primary diagnosis was $22,066/$15,912 in 2012. In multivariable-adjusted analyses, these factors were associated with higher ED charges: older age, female sex, highest income quartile, being uninsured, metropolitan residence, Western United States hospital location, heart disease, renal failure, heart failure, hypertension (HTN), diabetes, osteoarthritis (OA), and chronic obstructive pulmonary disease (COPD). These factors were associated with higher odds of hospitalization: older age, Northeast location, metropolitan teaching hospital, higher income quartile, heart disease, renal failure, heart failure, hyperlipidemia, HTN, diabetes, COPD, and OA, whereas self-pay insurance status was associated with lower odds of hospitalization, following an ED visit for gout. Conclusion. Absolute ED use and charges for gout increased over time, but relative use remained stable. Modifiable comorbidity factors associated with higher gout-related use should be targeted to reduce morbidity and healthcare use. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.; Yu, Shaohua] UAB, Sch Med, Dept Med, Birmingham, AL USA. [Singh, Jasvinder A.; Yu, Shaohua] UAB, Sch Publ Hlth, Div Epidemiol, Birmingham, AL USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com FU UAB Division of Rheumatology; US National Institute of Arthritis and Musculoskeletal and Skin Diseases [P50 AR060772] FX Supported by research funds from the UAB Division of Rheumatology and the resources and use of facilities at the Birmingham VA Medical Center. JAS is also supported by a grant from the US National Institute of Arthritis and Musculoskeletal and Skin Diseases (P50 AR060772). NR 20 TC 1 Z9 1 U1 1 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD AUG PY 2016 VL 43 IS 8 BP 1581 EP 1588 DI 10.3899/jrheum.151419 PG 8 WC Rheumatology SC Rheumatology GA DS6HG UT WOS:000380882300021 ER PT J AU Hou, LP Bergen, SE Akula, N Song, J Hultman, CM Landen, M Adli, M Alda, M Ardau, R Arias, B Aubry, JM Backlund, L Badner, JA Barrett, TB Bauer, M Baune, BT Bellivier, F Benabarre, A Bengesser, S Berrettini, WH Bhattacharjee, AK Biernacka, JM Birner, A Bloss, CS Brichant-Petitjean, C Bui, ET Byerley, W Cervantes, P Chillotti, C Cichon, S Colom, F Coryell, W Craig, DW Cruceanu, C Czerski, PM Davis, T Dayer, A Degenhardt, F Del Zompo, M DePaulo, JR Edenberg, HJ Etain, B Falkai, P Foroud, T Forstner, AJ Frisen, L Frye, MA Fullerton, JM Gard, S Garnham, JS Gershon, ES Goes, FS Greenwood, TA Grigoroiu-Serbanescu, M Hauser, J Heilbronner, U Heilmann-Heimbach, S Herms, S Hipolito, M Hitturlingappa, S Hoffmann, P Hofmann, A Jamain, S Jimenez, E Kahn, JP Kassem, L Kelsoe, JR Kittel-Schneider, S Kliwicki, S Koller, DL Konig, B Lackner, N Laje, G Lang, M Lavebratt, C Lawson, WB Leboyer, M Leckband, SG Liu, CY Maaser, A Mahon, PB Maier, W Maj, M Manchia, M Martinsson, L McCarthy, MJ McElroy, SL McInnis, MG McKinney, R Mitchell, PB Mitjans, M Mondimore, FM Monteleone, P Muhleisen, TW Nievergelt, CM Nothen, MM Novak, T Nurnberger, JI Nwulia, EA Osby, U Pfennig, A Potash, JB Propping, P Reif, A Reininghaus, E Rice, J Rietschel, M Rouleau, GA Rybakowski, JK Schalling, M Scheftner, WA Schofield, PR Schork, NJ Schulze, TG Schumacher, J Schweizer, BW Severino, G Shekhtman, T Shilling, PD Simhandl, C Slaney, CM Smith, EN Squassina, A Stamm, T Stopkova, P Streit, F Strohmaier, J Szelinger, S Tighe, SK Tortorella, A Turecki, G Vieta, E Volkert, J Witt, SH Wright, A Zandi, PP Zhang, P Zollner, S McMahon, FJ AF Hou, Liping Bergen, Sarah E. Akula, Nirmala Song, Jie Hultman, Christina M. Landen, Mikael Adli, Mazda Alda, Martin Ardau, Raffaella Arias, Barbara Aubry, Jean-Michel Backlund, Lena Badner, Judith A. Barrett, Thomas B. Bauer, Michael Baune, Bernhard T. Bellivier, Frank Benabarre, Antonio Bengesser, Susanne Berrettini, Wade H. Bhattacharjee, Abesh Kumar Biernacka, Joanna M. Birner, Armin Bloss, Cinnamon S. Brichant-Petitjean, Clara Bui, Elise T. Byerley, William Cervantes, Pablo Chillotti, Caterina Cichon, Sven Colom, Francesc Coryell, William Craig, David W. Cruceanu, Cristiana Czerski, Piotr M. Davis, Tony Dayer, Alexandre Degenhardt, Franziska Del Zompo, Maria DePaulo, J. Raymond Edenberg, Howard J. Etain, Bruno Falkai, Peter Foroud, Tatiana Forstner, Andreas J. Frisen, Louise Frye, Mark A. Fullerton, Janice M. Gard, Sebastien Garnham, Julie S. Gershon, Elliot S. Goes, Fernando S. Greenwood, Tiffany A. Grigoroiu-Serbanescu, Maria Hauser, Joanna Heilbronner, Urs Heilmann-Heimbach, Stefanie Herms, Stefan Hipolito, Maria Hitturlingappa, Shashi Hoffmann, Per Hofmann, Andrea Jamain, Stephane Jimenez, Esther Kahn, Jean-Pierre Kassem, Layla Kelsoe, John R. Kittel-Schneider, Sarah Kliwicki, Sebastian Koller, Daniel L. Koenig, Barbara Lackner, Nina Laje, Gonzalo Lang, Maren Lavebratt, Catharina Lawson, William B. Leboyer, Marion Leckband, Susan G. Liu, Chunyu Maaser, Anna Mahon, Pamela B. Maier, Wolfgang Maj, Mario Manchia, Mirko Martinsson, Lina McCarthy, Michael J. McElroy, Susan L. McInnis, Melvin G. McKinney, Rebecca Mitchell, Philip B. Mitjans, Marina Mondimore, Francis M. Monteleone, Palmiero Muehleisen, Thomas W. Nievergelt, Caroline M. Noethen, Markus M. Novak, Tomas Nurnberger, John I., Jr. Nwulia, Evaristus A. Osby, Urban Pfennig, Andrea Potash, James B. Propping, Peter Reif, Andreas Reininghaus, Eva Rice, John Rietschel, Marcella Rouleau, Guy A. Rybakowski, Janusz K. Schalling, Martin Scheftner, William A. Schofield, Peter R. Schork, Nicholas J. Schulze, Thomas G. Schumacher, Johannes Schweizer, Barbara W. Severino, Giovanni Shekhtman, Tatyana Shilling, Paul D. Simhandl, Christian Slaney, Claire M. Smith, Erin N. Squassina, Alessio Stamm, Thomas Stopkova, Pavla Streit, Fabian Strohmaier, Jana Szelinger, Szabolcs Tighe, Sarah K. Tortorella, Alfonso Turecki, Gustavo Vieta, Eduard Volkert, Julia Witt, Stephanie H. Wright, Adam Zandi, Peter P. Zhang, Peng Zollner, Sebastian McMahon, Francis J. TI Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder SO HUMAN MOLECULAR GENETICS LA English DT Article ID TO-CASE RATIO; X-CHROMOSOME; GENETIC ASSOCIATION; STATISTICAL POWER; SPECTRUM DISORDER; LITHIUM TREATMENT; COMPLEX TRAITS; RISK LOCI; SCHIZOPHRENIA; POPULATION AB Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behaviour. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used similar to 2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, P = 5.87 x 10(-9); odds ratio (OR) = 1.12) and markers within ERBB2 (rs2517959, P = 4.53 x 10(-9); OR = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS. C1 [Hou, Liping; Akula, Nirmala; Bui, Elise T.; Kassem, Layla; Laje, Gonzalo; Schulze, Thomas G.; McMahon, Francis J.] NIMH, Intramural Res Program, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Bergen, Sarah E.; Song, Jie; Hultman, Christina M.; Landen, Mikael] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Bergen, Sarah E.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Landen, Mikael] Gothenburg Univ, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden. [Adli, Mazda; Stamm, Thomas] Charite, Campus Charite Mitte, Dept Psychiat & Psychotherapy, Berlin, Germany. [Alda, Martin; Garnham, Julie S.; Slaney, Claire M.] Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada. [Ardau, Raffaella; Chillotti, Caterina] Hosp Univ Agcy Cagliari, Clin Pharmacol Unit, Cagliari, Italy. [Arias, Barbara; Mitjans, Marina] Univ Barcelona, CIBERSAM, Dept Biol Anim, Unitat Antropol Dp Biol Anim,Fac Biol, Barcelona, Spain. [Arias, Barbara; Mitjans, Marina] Univ Barcelona, CIBERSAM, Inst Biomed IBUB, Barcelona, Spain. [Aubry, Jean-Michel; Dayer, Alexandre] Univ Hosp Geneva, Mood Disorders Unit, Dept Mental Hlth & Psychiat, Geneva, Switzerland. [Backlund, Lena; Lavebratt, Catharina; Schalling, Martin] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden. [Backlund, Lena; Lavebratt, Catharina; Osby, Urban; Schalling, Martin] Karolinska Univ Hosp, Ctr Mol Med, Stockholm, Sweden. [Badner, Judith A.; Gershon, Elliot S.] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA. [Barrett, Thomas B.] Portland VA Med Ctr, Portland, OR USA. [Bauer, Michael; Pfennig, Andrea] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Psychiat & Psychotherapy, Dresden, Germany. [Baune, Bernhard T.; Davis, Tony; Hitturlingappa, Shashi] Univ Adelaide, Discipline Psychiat, Adelaide, SA, Australia. [Bellivier, Frank; Brichant-Petitjean, Clara] Univ Paris Diderot, INSERM UMR S 1144, Pole Psychiat, Grp Hosp Lariboisiere F Widal,AP HP, Paris, France. [Benabarre, Antonio; Colom, Francesc; Jimenez, Esther; Vieta, Eduard] Univ Barcelona, IDIBAPS, CIBERSAM, Bipolar Disorder Program,Inst Neurosci,Hosp Clin, Barcelona, Spain. [Bengesser, Susanne; Birner, Armin; Lackner, Nina; Reininghaus, Eva] Med Univ Graz, Special Outpatient Ctr Bipolar Affect Disorder, Graz, Austria. [Berrettini, Wade H.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Bhattacharjee, Abesh Kumar; Greenwood, Tiffany A.; Kelsoe, John R.; McKinney, Rebecca; Nievergelt, Caroline M.; Shekhtman, Tatyana; Shilling, Paul D.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Biernacka, Joanna M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Biernacka, Joanna M.; Frye, Mark A.] Mayo Clin, Dept Psychiat & Psychol, Rochester, MN USA. [Bloss, Cinnamon S.; Schork, Nicholas J.; Smith, Erin N.] Scripps Translat Sci Inst, La Jolla, CA USA. [Byerley, William] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Cervantes, Pablo] McGill Univ, Ctr Hlth, Disorders Program, Montreal, PQ, Canada. [Cichon, Sven; Degenhardt, Franziska; Forstner, Andreas J.; Heilmann-Heimbach, Stefanie; Herms, Stefan; Hoffmann, Per; Hofmann, Andrea; Maaser, Anna; Muehleisen, Thomas W.; Noethen, Markus M.; Propping, Peter; Schumacher, Johannes] Univ Bonn, Inst Human Genet, Bonn, Germany. [Cichon, Sven; Degenhardt, Franziska; Forstner, Andreas J.; Heilmann-Heimbach, Stefanie; Herms, Stefan; Hoffmann, Per; Hofmann, Andrea; Maaser, Anna; Muehleisen, Thomas W.; Noethen, Markus M.; Schumacher, Johannes] Univ Bonn, Life Brain Ctr, Dept Genom, Bonn, Germany. [Cichon, Sven; Hoffmann, Per; Muehleisen, Thomas W.] Res Ctr Julich, Inst Neurosci & Med INM 1, Julich, Germany. [Cichon, Sven; Herms, Stefan; Hoffmann, Per] Univ Basel, Div Med Genet, Basel, Switzerland. [Cichon, Sven; Herms, Stefan; Hoffmann, Per] Univ Basel, Dept Biomed, Basel, Switzerland. [Coryell, William] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. [Craig, David W.; Szelinger, Szabolcs] Translat Genom Res Inst, Phoenix, AZ USA. [Cruceanu, Cristiana; Turecki, Gustavo] McGill Univ, Douglas Mental Hlth Univ Inst, Montreal, PQ, Canada. [Czerski, Piotr M.; Hauser, Joanna] Poznan Univ Med Sci, Psychiat Genet Unit, Poznan, Poland. [Del Zompo, Maria; Manchia, Mirko; Severino, Giovanni; Squassina, Alessio] Univ Cagliari, Dept Biomed Sci, Cagliari, Italy. [DePaulo, J. Raymond; Goes, Fernando S.; Mahon, Pamela B.; Mondimore, Francis M.; Schulze, Thomas G.; Schweizer, Barbara W.] Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA. [Edenberg, Howard J.] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA. [Etain, Bruno; Jamain, Stephane; Leboyer, Marion] Univ Paris Est Creteil, INSERM U955, Psychiat Translat, Pole Psychiat & Addictol,Hop Univ Henri Mondor, Creteil, France. [Falkai, Peter] Ludwig Maximilians Univ Munchen, Dept Psychiat & Psychotherapy, Munich, Germany. [Foroud, Tatiana; Koller, Daniel L.] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. [Frisen, Louise; Martinsson, Lina] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. [Frisen, Louise] Child & Adolescent Psychiat Res Ctr, Stockholm, Sweden. [Fullerton, Janice M.] Neurosci Res Australia, Psychiat Genet, Sydney, NSW, Australia. [Fullerton, Janice M.; Schofield, Peter R.] Univ New South Wales, Sch Med Sci, Sydney, NSW 2052, Australia. [Gard, Sebastien] Hop Charles Perrens, Psychiat Serv, Bordeaux, France. [Grigoroiu-Serbanescu, Maria] Alexandru Obregia Clin Psychiat Hosp, Biometr Psychiat Genet Res Unit, Bucharest, Romania. [Heilbronner, Urs; Schulze, Thomas G.] Ludwig Maximilians Univ Munchen, Inst Psychiat Phen & Genom, Munich, Germany. [Heilbronner, Urs; Schulze, Thomas G.] Georg August Univ Gottingen, Univ Med Ctr, Dept Psychiat & Psychotherapy, Gottingen, Germany. [Hipolito, Maria; Lawson, William B.; Nwulia, Evaristus A.] Howard Univ Hosp, Dept Psychiat & Behav Sci, Washington, DC USA. [Kahn, Jean-Pierre] Univ Lorraine, Ctr Psychotherap Nancy, Serv Psychiat & Psychol Clin, Nancy, France. [Kittel-Schneider, Sarah; Reif, Andreas; Volkert, Julia] Univ Hosp Frankfurt, Dept Psychiat Psychosomat Med & Psychotherapy, Frankfurt, Germany. [Kliwicki, Sebastian; Rybakowski, Janusz K.] Poznan Univ Med Sci, Dept Adult Psychiat, Poznan, Poland. [Koenig, Barbara] Landesklinikum Neunkirchen, Dept Psychiat & Psychotherapeuth Med, Neunkirchen, Austria. [Lang, Maren; Rietschel, Marcella; Schulze, Thomas G.; Streit, Fabian; Strohmaier, Jana; Witt, Stephanie H.] Heidelberg Univ, Dept Genet Epidemiol Psychiat, Cent Inst Mental Hlth, Med Fac Mannheim, Mannheim, Germany. [Leckband, Susan G.] VA San Diego Healthcare Syst, Dept Pharm, San Diego, CA USA. [Liu, Chunyu] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. [Maier, Wolfgang] Univ Bonn, Dept Psychiat, Bonn, Germany. [Maj, Mario; Monteleone, Palmiero; Tortorella, Alfonso] Univ Naples SUN, Dept Psychiat, Naples, Italy. [Manchia, Mirko] Dalhousie Univ, Dept Pharmacol, Halifax, NS, Canada. [McCarthy, Michael J.] VA San Diego Healthcare Syst, Dept Psychiat, San Diego, CA USA. [McElroy, Susan L.] Univ Cincinnati, Coll Med, Lindner Ctr HOPE, Mason, OH USA. [McInnis, Melvin G.; Zhang, Peng; Zollner, Sebastian] Univ Michigan, Dept Psychiat, Ann Arbor, MI USA. [Mitchell, Philip B.; Wright, Adam] Univ New South Wales, Sch Psychiat, Sydney, NSW, Australia. [Mitchell, Philip B.; Wright, Adam] Black Dog Inst, Sydney, NSW, Australia. [Monteleone, Palmiero] Univ Salerno, Dept Med & Surg, Neurosci Sect, Salerno, Italy. [Novak, Tomas; Stopkova, Pavla] Natl Inst Mental Hlth, Klecany, Czech Republic. [Nurnberger, John I., Jr.] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. [Nurnberger, John I., Jr.] Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden. [Potash, James B.; Tighe, Sarah K.] Univ Iowa, Sch Med, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA. [Rice, John] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Rouleau, Guy A.] McGill Univ, Montreal Neurol Inst & Hosp, Montreal, PQ, Canada. [Scheftner, William A.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Schofield, Peter R.] Neurosci Res Australia, Mental Illness, Sydney, NSW, Australia. [Simhandl, Christian] Bipolar Ctr Wiener Neustadt, Wiener Neustadt, Austria. [Zandi, Peter P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. RP McMahon, FJ (reprint author), NIMH, Human Genet Branch, Intramural Res Program, 35 Convent Dr,Rm 1A201, Bethesda, MD 20892 USA. EM mcmahonf@mail.nih.gov OI Mitjans, Marina/0000-0001-5543-7320; Novak, Tomas/0000-0001-9156-9654; Squassina, Alessio/0000-0001-7415-7607; Maaser, Anna/0000-0002-9440-0712; Dayer, Alexandre/0000-0002-4490-9780 FU National Institute of Mental Health (NIMH) [ZIA-MH00284311]; NARSAD Young Investigator Award FX This work was supported by the National Institute of Mental Health (NIMH) Intramural Research Program (ZIA-MH00284311; NCT00001174) and a NARSAD Young Investigator Award to L.H. NR 62 TC 3 Z9 3 U1 4 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD AUG 1 PY 2016 VL 25 IS 15 BP 3383 EP 3394 DI 10.1093/hmg/ddw181 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA EJ2YK UT WOS:000393077300018 PM 27329760 ER PT J AU Newman, AB Sanders, JL Kizer, JR Boudreau, RM Odden, MC Al Hazzouri, AZ Arnold, AM AF Newman, Anne B. Sanders, Jason L. Kizer, Jorge R. Boudreau, Robert M. Odden, Michelle C. Al Hazzouri, Adina Zeki Arnold, Alice M. TI Trajectories of function and biomarkers with age: the CHS All Stars Study SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Ageing; disability; gait speed; grip strength; cognitive function; biomarkers ID CHRONIC KIDNEY-DISEASE; DISABLED OLDER WOMEN; DNA METHYLATION AGE; CARDIOVASCULAR HEALTH; CYSTATIN-C; DEHYDROEPIANDROSTERONE-SULFATE; PREDICT MORTALITY; BODY-COMPOSITION; GAIT SPEED; ALL-CAUSE AB Background: Multimorbidity is a major driver of physical and cognitive impairment, but rates of decline are also related to ageing. We sought to determine trajectories of decline in a large cohort by disease status, and examined their correspondence with biomarkers of ageing processes including growth hormone, sex steroid, inflammation, visceral adiposity and kidney function pathways. Methods: We have followed the 5888 participants in the Cardiovascular Health Study (CHS) for healthy ageing and longevity since 1989-90. Gait speed, grip strength, modified mini-mental status examination (3MSE) and the digit symbol substitution test (DSST) were assessed annually to 1998-99 and again in 2005-06. Insulin-like growth hormone (IGF-1), dehydroepiandrosterone sulphate (DHEAS), interleukin-6 (IL-6), adiponectin and cystatin-C were assessed 3-5 times from stored samples. Health status was updated annually and dichotomized as healthy vs not healthy. Trajectories for each function measure and biomarker were estimated using generalized estimating equations as a function of age and health status using standardized values. Results: Trajectories of functional decline showed strong age acceleration late in life in healthy older men and women as well as in chronically ill older adults. Adiponectin, IL-6 and cystatin-C tracked with functional decline in all domains; cystatin-C was consistently associated with functional declines independent of other biomarkers. DHEAS was independently associated with grip strength and IL-6 with grip strength and gait speed trajectories. Conclusion: Functional decline in late life appears to mark a fundamental ageing process in that it occurred and was accelerated in late life regardless of health status. Cystatin C was most consistently associated with these functional declines. C1 [Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Sanders, Jason L.] Massachusetts Gen Hosp, Harvard Affiliated Emergency Med Residency, Boston, MA 02114 USA. [Sanders, Jason L.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Kizer, Jorge R.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Boudreau, Robert M.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Odden, Michelle C.] Oregon State Univ, Dept Epidemiol, Corvallis, OR 97331 USA. [Al Hazzouri, Adina Zeki] Univ Miami, Dept Epidemiol, Miami, FL USA. [Arnold, Alice M.] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA. RP Newman, AB (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, A527 Crabtree Hall,130 DeSoto St, Pittsburgh, PA 15261 USA. EM newmana@edc.pitt.edu FU National Institute on Ageing (NIA) [AG023629, HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086]; National Heart, Lung, and Blood Institute (NHLBI) [HL080295]; University of Pittsburgh Claude D. Pepper Older Americans Independence Center [P30-AG-024827] FX This research was supported by AG023629 from the National Institute on Ageing (NIA) and contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083 and N01HC85086, and grant HL080295, from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by the University of Pittsburgh Claude D. Pepper Older Americans Independence Center: P30-AG-024827. NR 57 TC 1 Z9 1 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 EI 1464-3685 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD AUG PY 2016 VL 45 IS 4 BP 1135 EP 1145 DI 10.1093/ije/dyw092 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA EJ4JD UT WOS:000393182000028 PM 27272182 ER PT J AU Hsieh, DT Whiteway, SL Rohena, LO Thiele, EA AF Hsieh, David T. Whiteway, Susan L. Rohena, Luis O. Thiele, Elizabeth A. TI Tuberous sclerosis complex Five new things SO NEUROLOGY-CLINICAL PRACTICE LA English DT Review ID GIANT-CELL ASTROCYTOMA; NEUROPSYCHIATRIC DISORDERS TAND; INFANTILE SPASMS; EPILEPSY SURGERY; CORTICAL TUBERS; EVEROLIMUS; CHILDREN; VIGABATRIN; DIFFUSION; ABNORMALITIES AB Purpose of review: Tuberous sclerosis complex (TSC) is a variably expressed neurocutaneous genetic disorder characterized by hamartomatous growths inmultiple organ systems. Neurologic involvement often confers the most severe symptoms, and can include epilepsy, increased intracranial pressure from hydrocephalus, intellectual deficits, and autism. The purpose of this review is to provide a neurologically focused update in the diagnosis and treatment of these complications in patients with TSC. Recent findings: We highlight 5 new areas of understanding in TSC: the neurobiology of TSC and its translation into clinical practice, vigabatrin in the treatment of infantile spasms, the role of tubers and epilepsy surgery, the treatment of subependymal giant cell astrocytomas, and TSC-related neuropsychiatric disorders. Summary: These recent advances in diagnosis and treatment give our patients with TSC and their families hope for the future for improved care and possible preventive cures, to the end goal of improving quality of life. C1 [Hsieh, David T.] San Antonio Mil Med Ctr, Dept Pediat, Div Child Neurol, Jbsa Ft Sam Houston, TX USA. [Whiteway, Susan L.] San Antonio Mil Med Ctr, Dept Pediat, Div Hematol Oncol, Jbsa Ft Sam Houston, TX USA. [Rohena, Luis O.] San Antonio Mil Med Ctr, Dept Pediat, Div Med Genet, Jbsa Ft Sam Houston, TX USA. [Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Pediat Epilepsy Program, Boston, MA 02114 USA. RP Hsieh, DT (reprint author), San Antonio Mil Med Ctr, Dept Pediat, Div Child Neurol, Jbsa Ft Sam Houston, TX USA. EM david.t.hsieh.mil@mail.mil NR 46 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 2163-0402 EI 2163-0933 J9 NEUROL-CLIN PRACT JI Neurol.-Clin. Pract. PD AUG PY 2016 VL 6 IS 4 BP 339 EP 347 DI 10.1212/CPJ.0000000000000260 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA EJ3GW UT WOS:000393101600012 ER PT J AU Soni, NJ Franco-Sadud, R Schnobrich, D Dancel, R Tierney, DM Salame, G Restrepo, MI McHardy, P AF Soni, Nilam J. Franco-Sadud, Ricardo Schnobrich, Daniel Dancel, Ria Tierney, David M. Salame, Gerard Restrepo, Marcos I. McHardy, Paul TI Ultrasound guidance for lumbar puncture SO NEUROLOGY-CLINICAL PRACTICE LA English DT Review ID GUIDED SPINAL-ANESTHESIA; EPIDURAL-ANESTHESIA; EMERGENCY-DEPARTMENT; LANDMARKS; SPACE; ULTRASONOGRAPHY; LEVEL; IDENTIFICATION; VISUALIZATION; METAANALYSIS AB Purpose of review: To review the literature and describe techniques to use ultrasound to guide performance of lumbar puncture (LP). Recent findings: Ultrasound evaluation of the lumbar spine has been shown in randomized trials to improve LP success rates while reducing the number of attempts and the number of traumatic taps. Summary: Ultrasound mapping of the lumbar spine reveals anatomical information that is not obtainable by physical examination, including depth of the ligamentum flavum, width of the interspinous spaces, and spinal bone abnormalities, including scoliosis. Using static ultrasound, the lumbar spine anatomy is visualized in transverse and longitudinal planes and the needle insertion site is marked. Using real-time ultrasound guidance, the needle tip is tracked in a paramedian plane as it traverses toward the ligamentum flavum. Future research should focus on efficient methods to train providers, cost-effectiveness of ultrasound-guided LP, and the role of new needle-tracking technologies to facilitate the procedure. C1 [Soni, Nilam J.] South Texas Vet Hlth Care Syst, Sect Hosp Med, San Antonio, TX USA. [Soni, Nilam J.; Restrepo, Marcos I.] South Texas Vet Hlth Care Syst, Sect Pulm & Crit Care Med, San Antonio, TX USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Franco-Sadud, Ricardo] Med Coll Wisconsin, Div Gen Internal Med, Sect Hosp Med, Milwaukee, WI 53226 USA. [Schnobrich, Daniel] Univ Minnesota, Div Gen Internal Med, Minneapolis, MN USA. [Dancel, Ria] Univ N Carolina, Div Gen Med & Epidemiol, Chapel Hill, NC USA. [Tierney, David M.] Abbott NW Hosp, Dept Med Educ, Minneapolis, MN USA. [Salame, Gerard] Univ Colorado, Denver Hlth Hosp, Div Hosp Med, Boulder, CO 80309 USA. [McHardy, Paul] Sunnybrook Hlth Sci Ctr, Dept Anesthesia, Toronto, ON, Canada. RP Soni, NJ (reprint author), South Texas Vet Hlth Care Syst, Sect Hosp Med, San Antonio, TX USA.; Soni, NJ (reprint author), South Texas Vet Hlth Care Syst, Sect Pulm & Crit Care Med, San Antonio, TX USA. EM sonin@uthscsa.edu FU National Heart, Lung, and Blood Institute [K23HL096054] FX Partially supported by award K23HL096054 (MIR) from the National Heart, Lung, and Blood Institute. NR 42 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 2163-0402 EI 2163-0933 J9 NEUROL-CLIN PRACT JI Neurol.-Clin. Pract. PD AUG PY 2016 VL 6 IS 4 BP 358 EP 368 DI 10.1212/CPJ.0000000000000265 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA EJ3GW UT WOS:000393101600014 ER PT J AU Zapata, JA Widera, E AF Zapata, Josue A. Widera, Eric TI Partial Codes-A Symptom of a Larger Problem SO JAMA INTERNAL MEDICINE LA English DT Editorial Material C1 [Zapata, Josue A.] Univ Calif San Francisco, Dept Internal Med, San Francisco, CA 94143 USA. [Zapata, Josue A.] San Francisco VA Med Ctr, Div Hosp Med, San Francisco, CA USA. [Widera, Eric] San Francisco VA Med Ctr, Palliat Care & Hosp Serv, San Francisco, CA USA. [Widera, Eric] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. RP Zapata, JA (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Internal Med, 4150 Clement St,Bldg 203,1A-81, San Francisco, CA 94121 USA. EM josue.zapata@ucsf.edu NR 8 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 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD AUG PY 2016 VL 176 IS 8 BP 1058 EP 1059 DI 10.1001/jamainternmed.2016.2540 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA DT0AN UT WOS:000381145000005 PM 27295527 ER PT J AU Leventhal, JS Ross, MJ AF Leventhal, Jeremy S. Ross, Michael J. TI LAPping up dead cells to prevent lupus nephritis: a novel role for noncanonical autophagy in autoimmunity SO KIDNEY INTERNATIONAL LA English DT Editorial Material ID DEFICIENCY; CLEARANCE AB The mechanisms underlying the development of systemic lupus erythematosus and lupus nephritis remain poorly understood. A recent study demonstrates that deficiencies in the immune system's ability to degrade scavenged dead cells via noncanonical autophagy is sufficient to break immune tolerance and produce features commonly seen in lupus, including circulating autoantibodies, inflammatory cytokines, and nephritis. This work provides a possible mechanism for the association of polymorphisms in autophagy genes with the risk of lupus. C1 [Leventhal, Jeremy S.; Ross, Michael J.] Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, New York, NY 10029 USA. [Leventhal, Jeremy S.; Ross, Michael J.] James J Peters Bronx Vet Affairs Med Ctr, Div Renal, Bronx, NY USA. RP Leventhal, JS (reprint author), Icahn Sch Med Mt Sinai, Div Nephrol, 1 Gustave L Levy Pl,Box 1243, New York, NY 10029 USA. EM Jeremy.leventhal@mssm.edu FU NIDDK NIH HHS [K08 DK090217] NR 9 TC 0 Z9 0 U1 4 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD AUG PY 2016 VL 90 IS 2 BP 238 EP 239 DI 10.1016/j.kint.2016.06.001 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA EI6BZ UT WOS:000392581300001 PM 27418084 ER PT J AU Mino-Kenudson, M AF Mino-Kenudson, Mari TI Cons: Can liquid biopsy replace tissue biopsy?-the US experience SO TRANSLATIONAL LUNG CANCER RESEARCH LA English DT Editorial Material ID LUNG-CANCER PATIENTS; NUCLEIC-ACIDS; PLASMA DNA; ADENOCARCINOMA; CLASSIFICATION; BIOMARKERS; SOCIETY; NSCLC; CELLS C1 [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. RP Mino-Kenudson, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM mminokenudson@partners.org NR 20 TC 2 Z9 2 U1 2 U2 2 PU AME PUBL CO PI SHEUNG WAN PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG 00000, PEOPLES R CHINA SN 2218-6751 EI 2226-4477 J9 TRANSL LUNG CANCER R JI Transl. Lung Cancer Res. PD AUG PY 2016 VL 5 IS 4 BP 424 EP 427 DI 10.21037/tlcr.2016.08.01 PG 4 WC Oncology SC Oncology GA EI5QK UT WOS:000392549200010 PM 27655060 ER PT J AU Mino-Kenudson, M AF Mino-Kenudson, Mari TI Rebuttal from Dr. Mino-Kenudson SO TRANSLATIONAL LUNG CANCER RESEARCH LA English DT Editorial Material ID CIRCULATING TUMOR DNA; LUNG-CANCER PATIENTS; ADENOCARCINOMA; PLASMA; QUANTIFICATION; BIOMARKERS; EXPERIENCE; MUTATIONS; BIOPSIES; TISSUE C1 [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. RP Mino-Kenudson, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM mminokenudson@partners.org NR 17 TC 1 Z9 1 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 2218-6751 EI 2226-4477 J9 TRANSL LUNG CANCER R JI Transl. Lung Cancer Res. PD AUG PY 2016 VL 5 IS 4 BP 430 EP 432 DI 10.21037/tlcr.2016.08.02 PG 3 WC Oncology SC Oncology GA EI5QK UT WOS:000392549200012 PM 27657667 ER PT J AU Navar, AM Peterson, ED Li, S Goldberg, AC Virani, SS Roger, VL Robinson, JG Wilson, PWF Elassal, J Lee, LV Wang, TY AF Navar, A. M. Peterson, E. D. Li, S. Goldberg, A. C. Virani, S. S. Roger, V. L. Robinson, J. G. Wilson, P. W. F. Elassal, J. Lee, L. V. Wang, T. Y. TI Are clinicians following statin intensity recommendations? Insights in 135 U.S community practices in the PALM registry SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Navar, A. M.; Peterson, E. D.; Li, S.; Wang, T. Y.] Duke Clin Res Inst, Durham, NC USA. [Goldberg, A. C.] Washington Univ, Sch Med, St Louis, MO USA. [Virani, S. S.] VA Med Ctr, Houston, TX USA. [Roger, V. L.] Mayo Clin, Rochester, MN USA. [Robinson, J. G.] Univ Iowa, Iowa City, IA USA. [Wilson, P. W. F.] Emory Univ, Atlanta, GA 30322 USA. [Elassal, J.] Regeneron Pharmaceut Inc, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA. [Lee, L. V.] Sanofi Pharmaceut, Bridgewater, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA 273 BP 32 EP 32 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869500098 ER PT J AU Verjans, JW Ughi, GJ Osborn, EA Gerboud, EM Takx, RA Tawakol, A Tearney, GJ Jaffer, FA AF Verjans, J. W. Ughi, G. J. Osborn, E. A. Gerboud, E. M. Takx, R. A. Tawakol, A. Tearney, G. J. Jaffer, F. A. TI Multimodality intravascular molecular imaging of inflammation and endothelial permeability independently predicts plaque progression over time SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Verjans, J. W.] Univ Med Ctr Utrecht, Dept Cardiol, Utrecht, Netherlands. [Ughi, G. J.; Tearney, G. J.] Harvard Med Sch, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA. [Osborn, E. A.; Tawakol, A.; Jaffer, F. A.] Harvard Med Sch, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA USA. [Gerboud, E. M.] Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. [Takx, R. A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA P519 BP 51 EP 52 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869500157 ER PT J AU Stefanescu, A Armstrong, A Kennedy, KF Nykanen, D Aboulhosn, J Bhatt, AB AF Stefanescu, A. Armstrong, A. Kennedy, K. F. Nykanen, D. Aboulhosn, J. Bhatt, A. B. TI Risk factors for adverse events after catheter-based procedures in adolescents and adults with congenital heart disease - a report from the IMPACT registry SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Stefanescu, A.; Bhatt, A. B.] Massachusetts Gen Hosp, Cardiol, Boston, MA 02114 USA. [Armstrong, A.] Nationwide Childrens Hosp, Cardiol, St Louis, MO USA. [Kennedy, K. F.] St Lukes Hosp, Kansas City, MO USA. [Nykanen, D.] Arnold Palmer Hosp Children Cardiol & Cardiac Cat, Orlando, FL USA. [Aboulhosn, J.] Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA 1116 BP 201 EP 202 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869501030 ER PT J AU Wolsk, E Claggett, B Kober, L Diaz, R Dickstein, K Gerstein, HC Lawson, FC Bentley-Lewis, R Maggioni, AP McMurray, JJV Probstfield, JL Riddle, MC Solomon, SD Tardif, JC Pfeffer, MA AF Wolsk, E. Claggett, B. Kober, L. Diaz, R. Dickstein, K. Gerstein, H. C. Lawson, F. C. Bentley-Lewis, R. Maggioni, A. P. McMurray, J. J. V. Probstfield, J. L. Riddle, M. C. Solomon, S. D. Tardif, J. -C. Pfeffer, M. A. TI Changes in BNP prior to major cardiovascular events in patients with type 2 diabetes and a recent coronary event SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Wolsk, E.; Claggett, B.; Solomon, S. D.; Pfeffer, M. A.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Kober, L.] Copenhagen Univ Hosp, Rigshosp, Copenhagen, Denmark. [Diaz, R.] Estudios Cardiol Latinoamer ECLA, Rosario, Santa Fe, Argentina. [Dickstein, K.] Univ Bergen, Bergen, Norway. [Gerstein, H. C.] McMaster Univ, Hamilton, ON, Canada. [Lawson, F. C.] Sanofi US, Bridgewater, MA USA. [Bentley-Lewis, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Maggioni, A. P.] Assoc Nazl Med Cardiol Osped Res Ctr, Florence, Italy. [McMurray, J. J. V.] Cardiovasc Res Ctr Glasgow, Glasgow, Lanark, Scotland. [Probstfield, J. L.] Univ Washington, Seattle, WA 98195 USA. [Riddle, M. C.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Tardif, J. -C.] Montreal Heart Inst, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA P1173 BP 220 EP 220 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869501086 ER PT J AU Jiannan, J Xing, L Hou, J Jia, H Hu, S Tian, J Lin, L Li, L Zhu, Y Zheng, G Ren, X Yu, H Zhang, S Yu, B Jang, IK AF Jiannan, J. Xing, L. Hou, J. Jia, H. Hu, S. Tian, J. Lin, L. Li, L. Zhu, Y. Zheng, G. Ren, X. Yu, H. Zhang, S. Yu, B. Jang, I. K. TI Comparison of three chronic kidney disease epidemiology collaboration (CKD-EPI) equations for prediction of coronary plaque vulnerability: an optical coherence tomography study SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Jiannan, J.; Xing, L.; Hou, J.; Jia, H.; Hu, S.; Tian, J.; Lin, L.; Li, L.; Zhu, Y.; Zheng, G.; Ren, X.; Yu, H.; Zhang, S.; Yu, B.] Harbin Med Univ, Dept Cardiol, Affiliated Hosp 2, Harbin, Peoples R China. [Jang, I. K.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA 1309 BP 231 EP 231 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869501120 ER PT J AU Yin, O Miller, R Ruff, CT Morrow, D Antman, EM Mercuri, M Braunwald, E Giugliano, RP Truitt, K AF Yin, O. Miller, R. Ruff, C. T. Morrow, D. Antman, E. M. Mercuri, M. Braunwald, E. Giugliano, R. P. Truitt, K. TI Linking intrinsic factor X activity, a biologically relevant pharmacodynamic marker, to edoxaban plasma concentration and clinical outcomes in the ENGAGE AF-TIMI 48 trial SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Yin, O.; Miller, R.; Mercuri, M.; Truitt, K.] Daiichi Sankyo Pharma Dev, Edison, NJ USA. [Ruff, C. T.; Morrow, D.; Antman, E. M.; Braunwald, E.; Giugliano, R. P.] Brigham & Womens Hosp, TIMI Study Grp, Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA 1354 BP 234 EP 235 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869501130 ER PT J AU Zhu, YC Zheng, GH Hu, SN Jia, HB Dai, JN Li, LL Wang, C Afolabi, A Mustafina, I Hou, JB Zhang, SS Yu, B Jang, IK AF Zhu, Y. C. Zheng, G. H. Hu, S. N. Jia, H. B. Dai, J. N. Li, L. L. Wang, C. Afolabi, A. Mustafina, I. Hou, J. B. Zhang, S. S. Yu, B. Jang, I. K. TI Relation between lipid lowering therapy and plaque progression based on 10-year framingham risk score: an optical coherence tomography study SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Zhu, Y. C.; Zheng, G. H.; Hu, S. N.; Jia, H. B.; Dai, J. N.; Li, L. L.; Wang, C.; Afolabi, A.; Mustafina, I.; Hou, J. B.; Yu, B.] Harbin Med Univ, Dept Cardiol, Affiliated Hosp 2, Harbin, Peoples R China. [Zhang, S. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jang, I. K.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA P1382 BP 243 EP 243 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869501155 ER PT J AU Tanimoto, T Parsenghian, MH Petrov, AD Nakahara, T Kawai, H Nishimura, R Weisbart, RH Chan, G Richieri, RA Reynolds, GT Sengupta, PP Haider, N Blankenberg, FG Strauss, HW Narula, J AF Tanimoto, T. Parsenghian, M. H. Petrov, A. D. Nakahara, T. Kawai, H. Nishimura, R. Weisbart, R. H. Chan, G. Richieri, R. A. Reynolds, G. T. Sengupta, P. P. Haider, N. Blankenberg, F. G. Strauss, H. W. Narula, J. TI Cardioprotective effects of Fv-HSP70 injection on ischemic/reperfusion injury SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Tanimoto, T.; Petrov, A. D.; Nakahara, T.; Kawai, H.; Sengupta, P. P.; Haider, N.; Strauss, H. W.; Narula, J.] Mt Sinai Sch Med, Cardiol, New York, NY USA. [Parsenghian, M. H.; Richieri, R. A.; Reynolds, G. T.] Rubicon Biotechnol, Lake Forest, IL USA. [Nishimura, R.; Weisbart, R. H.] Univ Calif Los Angeles, Los Angeles, CA USA. [Chan, G.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Blankenberg, F. G.] Lucile Salter Packard Childrens Hosp, Stanford, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA P1801 BP 370 EP 370 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869501567 ER PT J AU Fanola, CL Giugliano, RP Trevisan, M Nordio, F Ruff, CT Antman, EM Braunwald, E AF Fanola, C. L. Giugliano, R. P. Trevisan, M. Nordio, F. Ruff, C. T. Antman, E. M. Braunwald, E. CA TIMI Study Grp TI A novel risk prediction score in atrial fibrillation for a net clinical outcome from the ENGAGE AF-TIMI 48 randomized clinical trial SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Fanola, C. L.; Giugliano, R. P.; Trevisan, M.; Nordio, F.; Ruff, C. T.; Antman, E. M.; Braunwald, E.; TIMI Study Grp] Brigham & Womens Hosp, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA 1876 BP 393 EP 394 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869501643 ER PT J AU Hilgendorf, I Lindau, A Haerdtner, C Hergeth, S Dufner, B Hoppe, N Stachon, P Willecke, F Wolf, D Robbins, CS Swirski, FK Libby, P Bode, C Zirlik, A AF Hilgendorf, I. Lindau, A. Haerdtner, C. Hergeth, S. Dufner, B. Hoppe, N. Stachon, P. Willecke, F. Wolf, D. Robbins, C. S. Swirski, F. K. Libby, P. Bode, C. Zirlik, A. TI SYK inhibitor fostamtinib protects from early but not established atherosclerosis when local macrophage proliferation dominates lesion turnover SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Hilgendorf, I.; Lindau, A.; Haerdtner, C.; Hergeth, S.; Dufner, B.; Hoppe, N.; Stachon, P.; Willecke, F.; Wolf, D.; Bode, C.; Zirlik, A.] Univ Freiburg, Heart Ctr Freiburg, Freiburg, Germany. [Robbins, C. S.] Toronto Gen Hosp, Toronto, ON, Canada. [Swirski, F. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Libby, P.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA P2408 BP 453 EP 454 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869502179 ER PT J AU Piccini, J Goodman, S Levitan, B Yuan, Z Hankey, GJ Singer, DE Becker, R Breithardt, G Berkowitz, S Halperin, J Nessel, C Hacke, W Mahaffey, KW Fox, KAA Patel, MR AF Piccini, J. Goodman, S. Levitan, B. Yuan, Z. Hankey, G. J. Singer, D. E. Becker, R. Breithardt, G. Berkowitz, S. Halperin, J. Nessel, C. Hacke, W. Mahaffey, K. W. Fox, K. A. A. Patel, M. R. CA ROCKET AF TI Net clinical benefit of rivaroxaban compared with warfarin in patients with atrial fibrillation SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Piccini, J.; Patel, M. R.] Duke Clin Res Inst, Durham, England. [Goodman, S.] Univ Toronto, Toronto, ON, Canada. [Levitan, B.; Yuan, Z.; Nessel, C.] Johnson & Johnson Pharmaceut, Raritan, NJ USA. [Hankey, G. J.] Univ Western Australia, Perth, WA, Australia. [Singer, D. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Becker, R.] Univ Cincinnati, Cincinnati, OH USA. [Breithardt, G.] Univ Med Ctr, Munster, Germany. [Berkowitz, S.] Bayer HealthCare Pharmaceut, Whippany, NJ USA. [Halperin, J.] Mt Sinai Sch Med, New York, NY USA. [Hacke, W.] Heidelberg Univ, Heidelberg, Germany. [Mahaffey, K. W.] Stanford Univ, Palo Alto, CA 94304 USA. [Fox, K. A. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. RI Hankey, Graeme /H-4968-2014 OI Hankey, Graeme /0000-0002-6044-7328 NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA P2566 BP 500 EP 500 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869502333 ER PT J AU Orgel, R Wojdyla, D Huberman, D Becker, RC Berkowitz, SD Breithardt, G Hacke, W Halperin, JL Hankey, GJ Mahaffey, KW Nessel, CC Singer, DE Fox, KAA Jones, WS Patel, MR AF Orgel, R. Wojdyla, D. Huberman, D. Becker, R. C. Berkowitz, S. D. Breithardt, G. Hacke, W. Halperin, J. L. Hankey, G. J. Mahaffey, K. W. Nessel, C. C. Singer, D. E. Fox, K. A. A. Jones, W. S. Patel, M. R. TI Systemic embolization in patients with atrial fibrillation: results from ROCKET AF SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Orgel, R.; Wojdyla, D.; Jones, W. S.; Patel, M. R.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Huberman, D.] North Carolina State Univ, Dept Stat, Raleigh, NC USA. [Becker, R. C.] Univ Cincinnati, Cincinnati, OH USA. [Berkowitz, S. D.] Bayer HealthCare, Whippany, NJ USA. [Breithardt, G.] Univ Hosp Munster, Munster, Germany. [Hacke, W.] Heidelberg Univ, Heidelberg, Germany. [Halperin, J. L.] Mt Sinai Sch Med, New York, NY USA. [Hankey, G. J.] Univ Western Australia, Sch Med & Pharmacol, Crawley, Australia. [Mahaffey, K. W.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Nessel, C. C.] Janssen Pharmaceut Res & Dev, Raritan, NJ USA. [Singer, D. E.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Fox, K. A. A.] Univ Edinburgh, Royal Infirm Edinburgh, Edinburgh, Midlothian, Scotland. RI Hankey, Graeme /H-4968-2014 OI Hankey, Graeme /0000-0002-6044-7328 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA P2602 BP 511 EP 511 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869502369 ER PT J AU Papafaklis, MI Vergallo, R Andreou, I Yonetsu, T Bourantas, CV Sakellarios, A Fotiadis, DI Feldman, CL Michalis, LK Jang, IK Stone, PH AF Papafaklis, M. I. Vergallo, R. Andreou, I. Yonetsu, T. Bourantas, C. V. Sakellarios, A. Fotiadis, D. I. Feldman, C. L. Michalis, L. K. Jang, I. K. Stone, P. H. TI Prediction of culprit lesions in patients with acute coronary syndrome by assessing the hemodynamic forces acting on plaques: a three-dimensional frequency-domain optical coherence tomography study SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Papafaklis, M. I.; Andreou, I.; Feldman, C. L.; Stone, P. H.] Harvard Med Sch, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA USA. [Vergallo, R.; Yonetsu, T.; Jang, I. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bourantas, C. V.] UCL, Dept Cardiovasc Sci, London, England. [Sakellarios, A.; Fotiadis, D. I.] Univ Ioannina, Dept Mat Sci, Ioannina, Greece. [Michalis, L. K.] Univ Ioannina, Sch Med, Dept Cardiol 2, Ioannina, Greece. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA 2988 BP 600 EP 600 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869503002 ER PT J AU Hu, S Jia, H Xing, L Hou, J Hang, L Zhang, S Yu, B Jang, IK AF Hu, S. Jia, H. Xing, L. Hou, J. Hang, L. Zhang, S. Yu, B. Jang, I. K. TI Vascular healing is delayed after drug-eluting stent implantation in patients with acute coronary syndromes caused by plaque erosion compared to plaque rupture: an optical coherence tomography study SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Hu, S.; Jia, H.; Hou, J.; Zhang, S.; Yu, B.] Harbin Med Univ, Dept Cardiol, Affiliated Hosp 2, Harbin, Peoples R China. [Xing, L.; Jang, I. K.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Hang, L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA 3079 BP 606 EP 607 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869503022 ER PT J AU Afolabi, A Hu, S Jia, H Li, L Dai, J Feng, L Zhu, Y Zheng, G Wang, C Dai, Z Mustafina, I Hou, J Zhang, S Yu, B Jang, I AF Afolabi, A. Hu, S. Jia, H. Li, L. Dai, J. Feng, L. Zhu, Y. Zheng, G. Wang, C. Dai, Z. Mustafina, I. Hou, J. Zhang, S. Yu, B. Jang, I. TI Does spotty calcification attenuate the plaque progression in non-culprit plaque underlying lipid-lowering therapy: an midterm optical coherence tomography study SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Afolabi, A.; Hu, S.; Jia, H.; Li, L.; Dai, J.; Feng, L.; Zhu, Y.; Zheng, G.; Wang, C.; Dai, Z.; Mustafina, I.; Hou, J.; Yu, B.] Harbin Med Univ, Affiliated Hosp 2, Harbin, Peoples R China. [Afolabi, A.; Hu, S.; Jia, H.; Li, L.; Dai, J.; Feng, L.; Zhu, Y.; Zheng, G.; Wang, C.; Dai, Z.; Mustafina, I.; Hou, J.; Yu, B.] Key Lab Myocardial Ischemia, Dept Cardiol, Harbin, Peoples R China. [Zhang, S.] Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Harbin, Peoples R China. [Jang, I.] Harvard Med Sch, Massachusetts Gen Hosp, Div Cardiol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA P3464 BP 680 EP 681 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869503262 ER PT J AU Piccini, J Washam, JB Simon, DN Thomas, LE Hylek, EM Fonarow, GC Mahaffey, KW Gersh, BJ Kowey, PR Ansell, JE Go, AS Reiffel, JA Singer, DE Pokorney, SD Peterson, ED AF Piccini, J. Washam, J. B. Simon, D. N. Thomas, L. E. Hylek, E. M. Fonarow, G. C. Mahaffey, K. W. Gersh, B. J. Kowey, P. R. Ansell, J. E. Go, A. S. Reiffel, J. A. Singer, D. E. Pokorney, S. D. Peterson, E. D. CA ORBIT AF Investigators TI Pharmacotherapy for atrial fibrillation in patients with chronic kidney disease: insights from the outcomes registry for better informed treatment of atrial fibrillation (ORBIT AF) SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Piccini, J.; Washam, J. B.; Simon, D. N.; Thomas, L. E.; Pokorney, S. D.; Peterson, E. D.] Duke Clin Res Inst, Durham, NC USA. [Hylek, E. M.] Boston Univ, Boston, MA 02215 USA. [Fonarow, G. C.] Univ Calif Los Angeles, Los Angeles, CA USA. [Mahaffey, K. W.] Stanford Univ, Palo Alto, CA 94304 USA. [Gersh, B. J.] Mayo Clin, Rochester, MN USA. [Kowey, P. R.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Ansell, J. E.] Lenox Hill Hosp, New York, NY 10021 USA. [Go, A. S.] Kaiser Permanente No Calif, Oakland, CA USA. [Reiffel, J. A.] Columbia Univ, New York, NY USA. [Singer, D. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA P3479 BP 685 EP 685 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869503277 ER PT J AU Halbach, M Abraham, WT Butter, C Ducharme, A Klug, D Little, WC Lovett, E Schafer, JE Senni, E Swarup, V Wachter, R Weaver, FA Zile, MR Muller-Ehmsen, J AF Halbach, M. Abraham, W. T. Butter, C. Ducharme, A. Klug, D. Little, W. C. Lovett, E. Schafer, J. E. Senni, E. Swarup, V. Wachter, R. Weaver, F. A. Zile, M. R. Muller-Ehmsen, J. TI Baroreflex activation therapy for the treatment of heart failure with reduced ejection fraction in patients with and without coronary artery disease SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Halbach, M.] Cologne Univ Hosp, Ctr Heart, Dept Internal Med 3, Cologne, Germany. [Abraham, W. T.] Ohio State Univ, Div Cardiovasc Med, Columbus, OH 43210 USA. [Butter, C.] Immanuel Heart Ctr Bernau, Med Sch Brandenburg, Dept Cardiol, Bernau, Germany. [Ducharme, A.] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada. [Klug, D.] Lille Univ Hosp, Dept Cardiol A, Lille, France. [Little, W. C.] Univ Mississippi, Med Ctr, Div Cardiol, Jackson, MS 39216 USA. [Lovett, E.] CVRx Inc, Minneapolis, MN USA. [Schafer, J. E.] NAMSA Inc, Dept Stat, Minneapolis, MN USA. [Senni, E.] Osped Papa Giovanni XXIII, Cardiovasc Dept, Bergamo, Italy. [Swarup, V.] Arizona Heart Hosp, Dept Electrophysiol, Phoenix, AZ USA. [Wachter, R.] Univ Med Gottingen, Gottingen, Germany. [Wachter, R.] German Cardiovasc Res Ctr, Clin Cardiol & Pneumol, Gottingen, Germany. [Weaver, F. A.] Univ Southern Calif, Div Vasc Surg & Endovasc Therapy, Keck Sch Med, Los Angeles, CA USA. [Zile, M. R.] Med Univ South Carolina, Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. [Muller-Ehmsen, J.] Asklepios Clin Altona, Dept Med, Hamburg, Germany. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA P3612 BP 724 EP 725 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869503409 ER PT J AU Wang, ZJ Zhang, LL Elmariah, S Zhou, YJ AF Wang, Z. J. Zhang, L. L. Elmariah, S. Zhou, Y. J. TI Prevalence and prognosis in patients with known or suspected myocardial ischemia but no obstructive coronary artery disease SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Wang, Z. J.; Zhang, L. L.; Zhou, Y. J.] Capital Med Univ, Anzhen Hosp, Beijing, Peoples R China. [Elmariah, S.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA 4067 BP 799 EP 799 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869504043 ER PT J AU Christophersen, IE Magnani, JW Yin, X Barnard, J Chung, M Lubitz, SA Benjamin, EJ Ellinor, PT AF Christophersen, I. E. Magnani, J. W. Yin, X. Barnard, J. Chung, M. Lubitz, S. A. Benjamin, E. J. Ellinor, P. T. CA CHARGE Investigators TI Meta-analyses in > 44,000 individuals identify fifteen genetic loci associated with the electrocardiographic P-wave SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Christophersen, I. E.; Lubitz, S. A.; Ellinor, P. T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Magnani, J. W.; Benjamin, E. J.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Yin, X.] NHLBI, Framingham, MA USA. [Yin, X.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Barnard, J.; Chung, M.] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA. [Barnard, J.; Chung, M.] Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH 44106 USA. [Barnard, J.; Chung, M.] Cleveland Clin, Dept Mol Cardiol, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA P4313 BP 841 EP 841 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869504173 ER PT J AU Soeda, T Uemura, S Vergallo, R Minami, Y Ong, DS Gao, L Lee, H Saito, Y Jang, IK AF Soeda, T. Uemura, S. Vergallo, R. Minami, Y. Ong, D. S. Gao, L. Lee, H. Saito, Y. Jang, I. K. TI Incidence and clinical impact of OCT findings after metallic stent implantation SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Soeda, T.; Saito, Y.] Nara Med Univ, Cardiol, Nara, Japan. [Uemura, S.] Kawasaki Med Univ, Cardiovasc Med, Kurashiki, Okayama, Japan. [Vergallo, R.] Univ Cattolica Sacro Cuore, Cardiovasc Sci, Rome, Italy. [Minami, Y.; Ong, D. S.; Gao, L.; Jang, I. K.] Massachusetts Gen Hosp, Cardiol, Boston, MA 02114 USA. [Lee, H.] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA P4406 BP 867 EP 867 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869504261 ER PT J AU Jia, HB Hu, S Rocco, V Liu, H Xu, M Soeda, T Minami, Y Hou, J Zhang, S Yu, B Jang, IK AF Jia, H. B. Hu, S. Rocco, V. Liu, H. Xu, M. Soeda, T. Minami, Y. Hou, J. Zhang, S. Yu, B. Jang, I. K. TI Progression of atherosclerotic plaques adjacent to the edges of drug-eluting stent: a 3-time optical coherence tomography and intravascular ultrasound study SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Jia, H. B.; Hu, S.; Liu, H.; Xu, M.; Hou, J.; Zhang, S.; Yu, B.] Harbin Med Univ, Affiliated Hosp 2, Key Lab Myocardial Ischemia, Dept Cardiol, Harbin, Peoples R China. [Rocco, V.; Soeda, T.; Minami, Y.; Jang, I. K.] Massachusetts Gen Hosp, Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA P4433 BP 874 EP 875 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869504288 ER PT J AU Beri, N Daniels, L Jaffe, AS Mueller, C Peacock, F Hollander, J Defilippi, C Anand, I Wu, A Apple, F Limkakeng, A Schreiber, D Nagurney, JT Clopton, P Maisel, A AF Beri, N. Daniels, L. Jaffe, A. S. Mueller, C. Peacock, F. Hollander, J. Defilippi, C. Anand, I. Wu, A. Apple, F. Limkakeng, A. Schreiber, D. Nagurney, J. T. Clopton, P. Maisel, A. TI Copeptin to rule out myocardial infarction in blacks versus Caucasians SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Beri, N.] Univ Calif San Diego, Internal Med, San Diego, CA 92103 USA. [Daniels, L.; Maisel, A.] Univ Calif San Diego, Internal Med, Cardiol, San Diego, CA 92103 USA. [Jaffe, A. S.] Mayo Clin, Cardiol, Internal Med, Rochester, MN USA. [Mueller, C.] Univ Hosp Basel, Cardiol, Internal Med, Basel, Switzerland. [Peacock, F.] Baylor Coll Med, Emergency Med, Houston, TX USA. [Hollander, J.] Thomas Jefferson Univ Hosp, Emergency Med, Philadelphia, PA USA. [Defilippi, C.] Univ Maryland, Cardiol, Internal Med, Baltimore, MD 21201 USA. [Anand, I.] Univ Minnesota, Internal Med, Cardiol, Minneapolis, MN USA. [Wu, A.] Univ Calif San Francisco, Lab Med, San Francisco, CA 94143 USA. [Apple, F.] Univ Minnesota, Lab Med & Pathol, Minneapolis, MN USA. [Limkakeng, A.] Duke Univ, Med Ctr, Emergency Med, Durham, NC 27706 USA. [Schreiber, D.] Stanford Univ, Emergency Med, Palo Alto, CA 94304 USA. [Nagurney, J. T.] Massachusetts Gen Hosp, Emergency Med, Boston, MA 02114 USA. [Clopton, P.] Vet Affairs San Diego Hlth Care Syst, Res, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA P4796 BP 981 EP 981 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869504650 ER PT J AU Sager, H Dutta, P Dahlman, J Hulsmans, M Courties, G Sun, Y Heidt, T Borodovsky, A Fitzgerald, K Libby, P Langer, R Weissleder, R Swirski, F Anderson, D Nahrendorf, M AF Sager, H. Dutta, P. Dahlman, J. Hulsmans, M. Courties, G. Sun, Y. Heidt, T. Borodovsky, A. Fitzgerald, K. Libby, P. Langer, R. Weissleder, R. Swirski, F. Anderson, D. Nahrendorf, M. TI Nanoparticle-enabled RNAi in endothelial cells attenuates inflammation in atherosclerosis and acute myocardial infarction SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Sager, H.] German Heart Ctr Munich, Dept Cardiol, Munich, Germany. [Dutta, P.] Univ Pittsburgh, Pittsburgh, PA USA. [Dahlman, J.; Langer, R.; Anderson, D.] MIT, Cambridge, MA 02139 USA. [Hulsmans, M.; Courties, G.; Sun, Y.; Weissleder, R.; Swirski, F.; Nahrendorf, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Heidt, T.] Univ Freiburg, Freiburg, Germany. [Borodovsky, A.; Fitzgerald, K.] Alnylam Pharmaceut, Cambridge, MA USA. [Libby, P.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA 4864 BP 989 EP 989 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869505011 ER PT J AU Arsiwala, T Van Tits, LJ Miranda, MX Nussbaum, K Weber, J Blyszczuk, P Stivala, S Beer, JH Greter, M Becher, B Hottiger, MO Mostoslavsky, R Eriksson, U Luescher, TF Matter, CM AF Arsiwala, T. Van Tits, L. J. Miranda, M. X. Nussbaum, K. Weber, J. Blyszczuk, P. Stivala, S. Beer, J. H. Greter, M. Becher, B. Hottiger, M. O. Mostoslavsky, R. Eriksson, U. Luescher, T. F. Matter, C. M. TI Bone marrow-specific Sirt6 deletion enhances atherosclerosis and foam cell formation via an increase in macrophage scavenger receptor 1 expression SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Arsiwala, T.; Van Tits, L. J.; Miranda, M. X.; Weber, J.; Blyszczuk, P.; Stivala, S.; Eriksson, U.] Univ Zurich, Ctr Mol Cardiol, Zurich, Switzerland. [Nussbaum, K.; Greter, M.; Becher, B.] Univ Zurich, Inst Expt Immunol, Zurich, Switzerland. [Beer, J. H.] Cantonal Hosp Baden, Internal Med, Baden, Switzerland. [Hottiger, M. O.] Univ Zurich, Dept Mol Mechanisms Dis, Zurich, Switzerland. [Mostoslavsky, R.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Luescher, T. F.; Matter, C. M.] Univ Zurich Hosp, Div Cardiol, Zurich, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA 4866 BP 990 EP 990 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869505013 ER PT J AU Bittner, D Mayrhofer, T Puchner, S Lu, M Maurovich-Horvat, P Ghemigian, K Kitslaar, P Broersen, A Bamberg, F Truong, Q Schlett, C Hoffmann, U Ferencik, M AF Bittner, D. Mayrhofer, T. Puchner, S. Lu, M. Maurovich-Horvat, P. Ghemigian, K. Kitslaar, P. Broersen, A. Bamberg, F. Truong, Q. Schlett, C. Hoffmann, U. Ferencik, M. TI Coronary CTA specific definitions of high-risk plaque features optimized for the detection of ACS: results from the ROMICAT II trial SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Bittner, D.; Mayrhofer, T.; Lu, M.; Ghemigian, K.; Hoffmann, U.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Puchner, S.] Med Univ Vienna, Vienna, Austria. [Maurovich-Horvat, P.] Semmelweis Univ, Budapest, Hungary. [Kitslaar, P.; Broersen, A.] Leiden Univ, Med Ctr, Leiden, Netherlands. [Bamberg, F.] Univ Tubingen, Tubingen, Germany. [Truong, Q.] Weill Cornell Med Coll, New York, NY USA. [Schlett, C.] Univ Heidelberg Hosp, Heidelberg, Germany. [Ferencik, M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 4 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA 5137 BP 1024 EP 1025 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869505117 ER PT J AU Jia, HB Hu, S Liu, H Xu, M Rocco, V Soeda, T Zhang, S Hou, J Yu, B Jang, IK AF Jia, H. B. Hu, S. Liu, H. Xu, M. Rocco, V. Soeda, T. Zhang, S. Hou, J. Yu, B. Jang, I. K. TI Degree of luminal narrowing and culprit plaque morphology in patients with acute coronary syndrome: an optical coherence tomography study SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Jia, H. B.; Hu, S.; Liu, H.; Xu, M.; Zhang, S.; Hou, J.; Yu, B.] Harbin Med Univ, Affiliated Hosp 2, Key Lab Myocardial Ischemia, Dept Cardiol, Harbin, Peoples R China. [Rocco, V.] Univ Cattolica Sacro Cuore, Cardiol, Rome, Italy. [Soeda, T.] Nara Med Univ, Nara, Japan. [Jang, I. K.] Massachusetts Gen Hosp, Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA P5288 BP 1068 EP 1068 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869505259 ER PT J AU Grapsa, J Tan, TC Howard, LSGE Dawson, D Gibbs, JSR Picard, MH Nihoyannopoulos, P AF Grapsa, J. Tan, T. C. Howard, L. S. G. E. Dawson, D. Gibbs, J. S. R. Picard, M. H. Nihoyannopoulos, P. TI Regression of RV mass and interventricular septal curvature duration predict mortality in patients with pre-capillary pulmonary hypertension: a follow up study SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Grapsa, J.; Howard, L. S. G. E.; Dawson, D.; Gibbs, J. S. R.; Nihoyannopoulos, P.] Hammersmith Hosp, London, England. [Tan, T. C.; Picard, M. H.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA 5752 BP 1187 EP 1187 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869505649 ER PT J AU Navar, AM Wang, TY Zakroysky, P Li, S Goldberg, AC Virani, SS Roger, VL Robinson, JG Wilson, PWF Lee, LV Elassal, J Peterson, ED AF Navar, A. M. Wang, T. Y. Zakroysky, P. Li, S. Goldberg, A. C. Virani, S. S. Roger, V. L. Robinson, J. G. Wilson, P. W. F. Lee, L. V. Elassal, J. Peterson, E. D. TI Patient receptiveness to statin therapy is higher when presented with lifetime risk rather than 10-year risk of cardiovascular disease: insights from the PALM registry SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Navar, A. M.; Wang, T. Y.; Zakroysky, P.; Li, S.; Peterson, E. D.] Duke Clin Res Inst, Durham, NC USA. [Goldberg, A. C.] Washington Univ, Sch Med, St Louis, MO USA. [Virani, S. S.] VA Med Ctr, Houston, TX USA. [Roger, V. L.] Mayo Clin, Rochester, MN USA. [Robinson, J. G.] Univ Iowa, Iowa City, IA USA. [Wilson, P. W. F.] Emory Univ, Atlanta, GA 30322 USA. [Lee, L. V.] Sanofi Pharmaceut, Bridgewater, NJ USA. [Elassal, J.] Regeneron Pharmaceut, Tarrytown, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA P5927 BP 1216 EP 1216 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869506080 ER PT J AU Beghetti, M Channick, R Chin, K Di Scala, L Gaine, S Ghofrani, HA Hoeper, M Lang, I McLaughlin, V Preiss, R Rubin, L Simonneau, G Sitbon, O Tapson, V Galie, N AF Beghetti, M. Channick, R. Chin, K. Di Scala, L. Gaine, S. Ghofrani, H. A. Hoeper, M. Lang, I. McLaughlin, V. Preiss, R. Rubin, L. Simonneau, G. Sitbon, O. Tapson, V. Galie, N. TI Selexipag for pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) after defect correction: insights from the randomized controlled GRIPHON study SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Beghetti, M.] Hop Enfants, Geneva, Switzerland. [Channick, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chin, K.] Univ Texas Southwestern Med Sch, Dallas, TX USA. [Di Scala, L.; Preiss, R.] Actel Pharmaceut Ltd, Allschwil, Switzerland. [Gaine, S.] Mater Misericordiae Univ Hosp, Natl Pulm Hypertens Unit, Dublin, Ireland. [Ghofrani, H. A.] Univ Giessen & Marburg Lung Ctr UGMLC, Giessen, Germany. [Hoeper, M.] Hannover Med Sch, Hannover, Germany. [Hoeper, M.] German Ctr Lung Res, Dept Resp Med, Hannover, Germany. [Lang, I.] Med Univ Vienna, Div Cardiol, Dept Internal Med 2, Allgemeines Krankenhaus, Vienna, Austria. [McLaughlin, V.] Univ Michigan Hlth Syst, Div Cardiovasc Med, Ann Arbor, MI USA. [Rubin, L.] Univ Calif San Diego, Div Pulm & Crit Care Med, San Diego, CA 92103 USA. [Simonneau, G.; Sitbon, O.] Univ Paris Sud, Hop Univ Bicetre, Le Kremlin Bicetre, France. [Tapson, V.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Galie, N.] Univ Bologna, Ist Malattie Apparato Cardiovasc, Bologna, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA 6092 BP 1243 EP 1243 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869506160 ER PT J AU Pawar, SP Kim, EJK Gupte, GG Afable, MA Strymish, JS Simon, SRS Orlander, JDO Vimalananda, VV AF Pawar, S. P. Kim, E. J. K. Gupte, G. G. Afable, M. A. Strymish, J. S. Simon, S. R. S. Orlander, J. D. O. Vimalananda, V. V. TI Variations in cardiology electronic consultation use in a large integrated healthcare system in the United States SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Pawar, S. P.] Boston Univ, Sch Med, Dept Internal Med, Boston, MA 02118 USA. [Kim, E. J. K.; Vimalananda, V. V.] Bedford Vet Affairs Med Ctr, Ctr Healthcare Org & Implementat Res, Bedford, MA USA. [Gupte, G. G.] Boston Univ, Sch Publ Hlth, Dept Hlth Law Policy & Management, Boston, MA USA. [Afable, M. A.; Simon, S. R. S.] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA USA. [Strymish, J. S.; Orlander, J. D. O.] VA Boston Healthcare Syst, West Roxbury, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA P6168 BP 1264 EP 1264 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869506226 ER PT J AU Celeng, C Maurovich-Horvat, P Ghoshhajra, BB Merkely, B Leiner, T Takx, RAP AF Celeng, C. Maurovich-Horvat, P. Ghoshhajra, B. B. Merkely, B. Leiner, T. Takx, R. A. P. TI Prognostic value of obstructive coronary artery disease on CTA in diabetic patients: a meta-analysis SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 27-31, 2016 CL Rome, ITALY SP European Soc Cardiol C1 [Celeng, C.; Maurovich-Horvat, P.; Merkely, B.] Semmelweis Univ, MTA SE Cardiovasc Imaging Res Grp, Heart & Vasc Ctr, Budapest, Hungary. [Ghoshhajra, B. B.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Cardiac MRI PET CT Prog, Boston, MA USA. [Leiner, T.; Takx, R. A. P.] Univ Med Ctr Utrecht, Radiol, Utrecht, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2016 VL 37 SU 1 MA 6604 BP 1397 EP 1397 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW7YL UT WOS:000383869506651 ER PT J AU Bateman, BT Huybrechts, KF Cohen, J Mogun, H Desai, RJ Patorno, E Hernandez-Diaz, S AF Bateman, Brian T. Huybrechts, Krista F. Cohen, Jacqueline Mogun, Helen Desai, Rishi J. Patorno, Elisabetta Hernandez-Diaz, Sonia TI Pregnancy Outcomes in Women with Chronic Hypertension Initiated on Labetalol versus Methyldopa SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Bateman, Brian T.; Huybrechts, Krista F.; Mogun, Helen; Desai, Rishi J.; Patorno, Elisabetta] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 75 Francis St, Boston, MA 02115 USA. [Bateman, Brian T.; Huybrechts, Krista F.; Mogun, Helen; Desai, Rishi J.; Patorno, Elisabetta] Harvard Med Sch, Boston, MA USA. [Cohen, Jacqueline; Hernandez-Diaz, Sonia] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2016 VL 25 SU S3 MA 21 BP 15 EP 16 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DY9VP UT WOS:000385483501021 ER PT J AU Esposito, DB Yin, R Russo, LJ del Carmen, MG Goldstein, SR Patsner, B Lanes, SF AF Esposito, Daina B. Yin, Ruihua Russo, Leo J. del Carmen, Marcela G. Goldstein, Steven R. Patsner, Bruce Lanes, Stephan F. TI Development and Validation of an Algorithm to Identify Endometrial Adenocarcinoma in US Administrative Claims Data SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Esposito, Daina B.; Yin, Ruihua; Lanes, Stephan F.] HealthCore Inc, Safety & Epidemiol, Andover, MA USA. [Russo, Leo J.] Pfizer Inc, Collegeville, PA USA. [del Carmen, Marcela G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Goldstein, Steven R.] NYU, Sch Med, New York, NY USA. [Patsner, Bruce] Inova Hlth Syst, Fairfax, VA 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 AUG PY 2016 VL 25 SU S3 MA 267 BP 159 EP 160 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DY9VP UT WOS:000385483501265 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, Bateman T. TI Detection of Aberrant Opioid Use in Prescription Claims Data: Comparison and Validation of Five Algorithms SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Rough, Kathryn; Hernandez-Diaz, Sonia] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Rough, Kathryn; Huybrechts, Krista F.; Desai, Rishi J.; Patorno, Elisabetta; Bateman, Bateman T.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 75 Francis St, Boston, MA 02115 USA. [Rough, Kathryn; Huybrechts, Krista F.; Desai, Rishi J.; Patorno, Elisabetta; Bateman, Bateman T.] Harvard Med Sch, Boston, MA USA. [Bateman, Bateman 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 AUG PY 2016 VL 25 SU S3 MA 369 BP 216 EP 216 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DY9VP UT WOS:000385483502005 ER PT J AU Park, Y Hernandez-Diaz, S Bateman, BT Cohen, J Patorno, E Mogun, H Huybrechts, KF AF Park, Yoonyoung Hernandez-Diaz, Sonia Bateman, Brian T. Cohen, Jacqueline Patorno, Elisabetta Mogun, Helen Huybrechts, Krista F. TI Continuation of Atypical Antipsychotic Medications During Pregnancy and the Risk of Gestational Diabetes SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Park, Yoonyoung; Bateman, Brian T.; Patorno, Elisabetta; Mogun, Helen; Huybrechts, Krista F.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 75 Francis St, Boston, MA 02115 USA. [Park, Yoonyoung; Bateman, Brian T.; Patorno, Elisabetta; Mogun, Helen; Huybrechts, Krista F.] Harvard Med Sch, Boston, MA USA. [Park, Yoonyoung; Hernandez-Diaz, Sonia; Cohen, Jacqueline] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesiol 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 AUG PY 2016 VL 25 SU S3 MA 404 BP 235 EP 236 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DY9VP UT WOS:000385483502037 ER PT J AU Huybrechts, KF Bateman, BT Hernandez-Diaz, S Desai, RJ Rough, K Mogun, H Patorno, E AF Huybrechts, Krista F. Bateman, Brian T. Hernandez-Diaz, Sonia Desai, Rishi J. Rough, Kathryn Mogun, Helen Patorno, Elisabetta TI Psychotropic Medications and the Risk of Neonatal Withdrawal SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Huybrechts, Krista F.; Bateman, Brian T.; Desai, Rishi J.; Rough, Kathryn; Mogun, Helen; Patorno, Elisabetta] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Huybrechts, Krista F.; Bateman, Brian T.; Desai, Rishi J.; Rough, Kathryn; Mogun, Helen; Patorno, Elisabetta] Harvard Med Sch, Boston, MA USA. [Bateman, Brian T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hernandez-Diaz, Sonia; Rough, Kathryn] Harvard TH Chan 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 AUG PY 2016 VL 25 SU S3 MA 444 BP 260 EP 260 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DY9VP UT WOS:000385483502077 ER PT J AU Park, Y Bateman, BT Kim, D Hernandez-Diaz, S Patorno, E Glynn, RJ Mogun, H Huybrechts, KF AF Park, Yoonyoung Bateman, Brian T. Kim, Dae Hernandez-Diaz, Sonia Patorno, Elisabetta Glynn, Robert J. Mogun, Helen Huybrechts, Krista F. TI Comparative Safety of Antipsychotic Medications in Hospitalized Myocardial Infarction Patients SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Park, Yoonyoung; Bateman, Brian T.; Kim, Dae; Patorno, Elisabetta; Glynn, Robert J.; Mogun, Helen; Huybrechts, Krista F.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 75 Francis St, Boston, MA 02115 USA. [Park, Yoonyoung; Bateman, Brian T.; Kim, Dae; Patorno, Elisabetta; Glynn, Robert J.; Mogun, Helen; Huybrechts, Krista F.] Harvard Med Sch, Boston, MA USA. [Park, Yoonyoung; Hernandez-Diaz, Sonia] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. [Kim, Dae] Beth Israel Deaconess Med Ctr, Dept Med, Div Gerontol, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2016 VL 25 SU S3 MA 447 BP 262 EP 262 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DY9VP UT WOS:000385483502080 ER PT J AU Cohen, JM Patorno, E Huybrechts, KF Park, Y Bateman, BT Hernandez-Diaz, S AF Cohen, Jacqueline M. Patorno, Elisabetta Huybrechts, Krista F. Park, Yoonyoung Bateman, Brian T. Hernandez-Diaz, Sonia TI Mood Stabilizer Use and Risk of Ischemic Placental Disease SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Cohen, Jacqueline M.; Park, Yoonyoung; Hernandez-Diaz, Sonia] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Patorno, Elisabetta; Huybrechts, Krista F.; Park, Yoonyoung; Bateman, Brian T.] Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Patorno, Elisabetta; Huybrechts, Krista F.; Park, Yoonyoung; Bateman, Brian T.] Harvard Med Sch, 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 AUG PY 2016 VL 25 SU S3 MA 507 BP 297 EP 297 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DY9VP UT WOS:000385483502140 ER PT J AU Bateman, BT Huybrechts, KF Booth, J Briggs, H Flood, P Bauer, M Landau, R AF Bateman, Brian T. Huybrechts, Krista F. Booth, Jessica Briggs, Holly Flood, Pamela Bauer, Melissa Landau, Ruth TI Opioid Use Following Discharge After Cesarean Delivery SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Bateman, Brian T.; Huybrechts, Krista F.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 75 Francis St, Boston, MA 02115 USA. [Bateman, Brian T.; Huybrechts, Krista F.; Briggs, Holly] Harvard Med Sch, Boston, MA USA. [Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. [Booth, Jessica] Wake Forest Univ, Dept Anesthesiol, Winston Salem, NC 27109 USA. [Briggs, Holly] Brigham & Womens Hosp, Dept Anesthesiol, 75 Francis St, Boston, MA 02115 USA. [Flood, Pamela] Stanford Univ, Dept Anesthesiol, Palo Alto, CA 94304 USA. [Bauer, Melissa] Univ Michigan, Dept Anesthesiol, Ann Arbor, MI 48109 USA. [Landau, Ruth] Columbia Univ, Dept Anesthesiol, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2016 VL 25 SU S3 MA 567 BP 330 EP 331 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DY9VP UT WOS:000385483502199 ER PT J AU Rough, K Hernandez-Diaz, S Huybrechts, KF Desai, RJ Patorno, E Bateman, BT AF Rough, Kathryn Hernandez-Diaz, Sonia Huybrechts, Krista F. Desai, Rishi J. Patorno, Elisabetta Bateman, Brian T. TI Increase in Aberrant Prescription Opioid Use by Pregnant Women in a Nationwide Cohort of Medicaid Beneficiaries SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Rough, Kathryn; Hernandez-Diaz, Sonia] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Rough, Kathryn; Huybrechts, Krista F.; Desai, Rishi J.; Patorno, Elisabetta; Bateman, Brian T.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 75 Francis St, 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 AUG PY 2016 VL 25 SU S3 MA 569 BP 331 EP 332 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DY9VP UT WOS:000385483502201 ER PT J AU Bachert, C Hellings, P Mullol, J Hamilos, D Naclerio, R Joish, VN Mannent, L Evans, R Abbe, A Amand, C Taniou, C Zhang, D Fan, C Pirozzi, G Graham, N Mastey, V Mahajan, S Staudinger, H Eckert, L Khan, A AF Bachert, C. Hellings, P. Mullol, J. Hamilos, D. Naclerio, R. Joish, V. N. Mannent, L. Evans, R. Abbe, A. Amand, C. Taniou, C. Zhang, D. Fan, C. Pirozzi, G. Graham, N. Mastey, V Mahajan, S. Staudinger, H. Eckert, L. Khan, A. TI Dupilumab improves health-related quality of life and absenteeism in nasal polyposis patients: results from a phase 2a trial SO ALLERGY LA English DT Meeting Abstract CT Meeting of the European-Academy-of-Allergy-and-Clinical-Immunology CY JUN 11-15, 2016 CL Vienna, AUSTRIA SP European Acad Allergy & Clin Immunol C1 [Bachert, C.] Ghent Univ Hosp, Ghent, Belgium. [Hellings, P.] Univ Hosp Leuven, Dept Otorhinolaryngol Head & Neck Surg, Leuven, Belgium. [Mullol, J.] Hosp Clin IDIBAPS, Clin & Expt Resp Immunoallergy, Barcelona, Spain. [Hamilos, D.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Naclerio, R.] Univ Chicago, Chicago, IL 60637 USA. [Joish, V. N.; Evans, R.; Graham, N.; Mastey, V] Regeneron Pharmaceut Inc, Tarrytown, NY USA. [Mannent, L.; Abbe, A.; Amand, C.; Eckert, L.; Khan, A.] Sanofi R&D, Chilly Mazarin, France. [Taniou, C.] Experis IT, Chilly Mazarin, France. [Zhang, D.; Fan, C.; Pirozzi, G.; Mahajan, S.; Staudinger, H.] Sanofi R&D, Bridgewater, 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 AUG PY 2016 VL 71 SU 102 SI SI MA 19 BP 12 EP 12 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DW5JI UT WOS:000383679800020 ER PT J AU Hourihane, J Allen, K Shreffler, W Dunngalvin, G Baumert, J Zurzolo, G Gurrin, L Dunngalvin, A Nordlee, J Taylor, S AF Hourihane, J. Allen, K. Shreffler, W. Dunngalvin, G. Baumert, J. Zurzolo, G. Gurrin, L. Dunngalvin, A. Nordlee, J. Taylor, S. TI Peanut allergen threshold study: validation of eliciting doses using a novel, single-dose challenge protocol SO ALLERGY LA English DT Meeting Abstract CT Meeting of the European-Academy-of-Allergy-and-Clinical-Immunology CY JUN 11-15, 2016 CL Vienna, AUSTRIA SP European Acad Allergy & Clin Immunol C1 [Hourihane, J.] Univ Coll Cork, Cork, Ireland. [Allen, K.; Zurzolo, G.] Murdoch Childrens Res Inst, Melbourne, Vic, Australia. [Shreffler, W.] Harvard Med Sch, Massachusetts Gen Hosp, Food Allergy Ctr, Boston, MA USA. [Shreffler, W.] Ctr Immunol & Inflammatory Dis, Boston, MA USA. [Dunngalvin, G.; Dunngalvin, A.] Univ Coll, Appl Psychol, Cork, Ireland. [Baumert, J.; Nordlee, J.; Taylor, S.] Univ Nebraska, Food Allergy Res & Resource Program, Lincoln, NE USA. [Gurrin, L.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Melbourne, Vic, Australia. 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 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD AUG PY 2016 VL 71 SU 102 SI SI MA 1364 BP 104 EP 104 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DW5JI UT WOS:000383679800208 ER PT J AU Burke, TF Ahn, R Nelson, BD Hines, R Kamara, J Oguttu, M Dulo, L Achieng, E Achieng, B Natarajan, A Maua, J Kargbo, SAS Altawil, Z Tester, K de Redon, E Niang, M Abdalla, K Eckardt, MJ AF Burke, T. F. Ahn, R. Nelson, B. D. Hines, R. Kamara, J. Oguttu, M. Dulo, L. Achieng, E. Achieng, B. Natarajan, A. Maua, J. Kargbo, S. A. S. Altawil, Z. Tester, K. de Redon, E. Niang, M. Abdalla, K. Eckardt, M. J. TI A postpartum haemorrhage package with condom uterine balloon tamponade: a prospective multi-centre case series in Kenya, Sierra Leone, Senegal, and Nepal SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Article DE Maternal mortality; postpartum haemorrhage; uterine balloon tamponade ID MATERNAL DEATH; BAKRI BALLOON; MANAGEMENT AB Objective To evaluate the effectiveness and safety of an ultra-low-cost uterine balloon tamponade package (ESM-UBT (TM)) for facility-based management of uncontrolled postpartum haemorrhage (PPH) in Kenya, Sierra Leone, Senegal, and Nepal. Design Prospective multi-centre case series. Setting Facilities in resource-scarce areas of Kenya, Sierra Leone, Nepal, and Senegal. Population Women with uncontrolled postpartum haemorrhage in 307 facilities across the four countries. Methods A standardised ESM-UBT package was implemented in 307 facilities over 29 months (1 September 2012 to 1 February 2015). Data were collected via a multi-pronged approach including data card completion, chart reviews, and provider interviews. Beginning in August 2014, women who had previously undergone UBT placement were sought and queried regarding potential complications associated with UBT use. Main outcome measures All-cause survival, survival from PPH, and post-UBT use complications (surgery, hospitalisation, antibiotics for pelvic infection) associated with UBT use. Results 201 UBTs were placed for uncontrolled vaginal haemorrhage refractory to all other interventions. In all, 38% (71/188) of women were either unconscious or confused at the time of UBT insertion. All-cause survival was 95% (190/201). However, 98% (160/163) of women survived uncontrolled PPH if delivery occurred at an ESM-UBT online facility. One (1/151) potential UBT-associated complication (postpartum endometritis) was identified and two improvised UBTs were placed in women with a ruptured uterus. Conclusions These pilot data suggest that the ESM-UBT package is a clinically promising and safe method to arrest uncontrolled postpartum haemorrhage and save women's lives. The UBT was successfully placed by all levels of facility-based providers. Future studies are needed to further evaluate the effectiveness of ESM-UBT in low-resource settings. C1 [Burke, T. F.; Ahn, R.; Nelson, B. D.; Hines, R.; Kamara, J.; Natarajan, A.; Altawil, Z.; Tester, K.; de Redon, E.; Eckardt, M. J.] Massachusetts Gen Hosp, Dept Emergency Med, Div Global Hlth & Human Rights, Zero Emerson Pl,Suite 104, Boston, MA 02114 USA. [Burke, T. F.; Ahn, R.; Nelson, B. D.; Natarajan, A.] Harvard Med Sch, Boston, MA USA. [Oguttu, M.; Dulo, L.; Achieng, E.; Achieng, B.] Kisumu Med & Educ Trust, Kisumu, Kenya. [Maua, J.] Minist Hlth, Div Reprod & Maternal Hlth, Nairobi, Kenya. [Kargbo, S. A. S.] Minist Hlth & Sanitat, Div Reprod Hlth, Freetown, Sierra Leone. [Niang, M.] Ctr Format & Rech Sante Reprod, Dakar, Senegal. [Abdalla, K.] UNICEF, Nairobi, Kenya. [Eckardt, M. J.] Boston Med Ctr, Dept Obstet & Gynecol, Boston, MA USA. RP Burke, TF (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Div Global Hlth & Human Rights, Zero Emerson Pl,Suite 104, Boston, MA 02114 USA. EM tfburke@partners.org OI Nelson, Brett/0000-0002-5049-1798 FU Izumi Foundation; Ujenzi Charitable Trust; Humanitarian Innovation Fund; United States Agency for International Development (USAID); Government of Norway; Bill & Melinda Gates Foundation; Grand Challenges Canada; UK Government FX The Every Second Matters for Mothers and Babies Uterine Balloon Tamponade research program (ESM-UBT TM) is made possible through the generous support of the Izumi Foundation, the Ujenzi Charitable Trust, the Humanitarian Innovation Fund and the Saving Lives at Birth partners: the United States Agency for International Development (USAID), the Government of Norway, the Bill & Melinda Gates Foundation, Grand Challenges Canada, and the UK Government. This manuscript was prepared by MGH and does not necessarily reflect the views of the funding partners. NR 14 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1470-0328 EI 1471-0528 J9 BJOG-INT J OBSTET GY JI BJOG PD AUG PY 2016 VL 123 IS 9 BP 1532 EP 1540 DI 10.1111/1471-0528.13550 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DW3SS UT WOS:000383563700026 PM 26223284 ER PT J AU Otto, MW Pollack, MH Dowd, SM Hofmann, SG Pearlson, G Szuhany, KL Gueorguieva, R Krystal, JH Simon, NM Tolin, DF AF Otto, Michael W. Pollack, Mark H. Dowd, Sheila M. Hofmann, Stefan G. Pearlson, Godfrey Szuhany, Kristin L. Gueorguieva, Ralitza Krystal, John H. Simon, Naomi M. Tolin, David F. TI RANDOMIZED TRIAL OF D-CYCLOSERINE ENHANCEMENT OF COGNITIVE-BEHAVIORAL THERAPY FOR PANIC DISORDER SO DEPRESSION AND ANXIETY LA English DT Article DE anxiety; panic attacks/agoraphobia; CBT; clinical trials; pharmacotherapy ID OBSESSIVE-COMPULSIVE DISORDER; SOCIAL ANXIETY DISORDER; EXPOSURE SESSIONS; FEAR EXTINCTION; PSYCHOTHERAPY; ANTIDEPRESSANT; AGORAPHOBIA; SCALE; PHARMACOTHERAPY; COMBINATION AB Background: Initial studies have provided a mixed perspective of the efficacy of d-cycloserine (DCS) for augmenting the efficacy of exposure-based cognitive behavioral therapy (CBT) for panic disorder. In this multicenter trial, we examine the magnitude of DCS augmentation effects for an ultra-brief program of CBT. Methods: We conducted a double-blind, controlled trial at three treatment sites, randomizing 180 adults with a primary diagnosis of panic disorder to five sessions of treatment, with study pill (50 mg DCS or matching placebo) administered 1 hr prior to the final three sessions. Two booster sessions were subsequently provided, and outcome was assessed at posttreatment and 1-month, 2-month, and 6-month follow-up assessments. The primary outcome was the degree of reduction in the Panic Disorder Severity Scale. Additional analyses examined the role of severity and current antidepressant or benzodiazepine use as moderators of DCS augmentation effects. Results: DCS augmentation resulted in significant benefit only early in the trial, with no beneficial effects of DCS augmentation evident at follow-up evaluations. We did not find that baseline severity or antidepressant or benzodiazepine use moderated DCS efficacy, but benzodiazepine use was associated with lower efficacy of CBT regardless of augmentation condition. Conclusions: Consistent with other recent multicenter trials, the benefit of DCS was less than indicated by pilot study and reflected an acceleration of treatment response evident at treatment endpoint, but no advantage in response over follow-up evaluation. Our results did not support severity or concomitant medication moderators observed in previous trials of DCS augmentation. (C) 2016 Wiley Periodicals, Inc. C1 [Otto, Michael W.; Hofmann, Stefan G.; Szuhany, Kristin L.] Boston Univ, Dept Psychol & Brain Sci, 648 Beacon St,5th Floor, Boston, MA 02215 USA. [Pollack, Mark H.; Dowd, Sheila M.] Rush Univ, Med Ctr, Dept Psychiat, Chicago, IL 60612 USA. [Pearlson, Godfrey; Tolin, David F.] Inst Living, Hartford, CT USA. [Pearlson, Godfrey; Tolin, David F.] Yale Univ, Sch Med, Hartford, CT USA. [Gueorguieva, Ralitza] Yale Univ, Sch Publ Hlth, Dept Biostat, New Haven, CT USA. [Krystal, John H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Krystal, John H.] Yale New Haven Med Ctr, 20 York St, New Haven, CT 06504 USA. [Simon, Naomi M.] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. [Simon, Naomi M.] Harvard Med Sch, Boston, MA USA. RP Otto, MW (reprint author), Boston Univ, Dept Psychol & Brain Sci, 648 Beacon St,5th Floor, Boston, MA 02215 USA. EM mwotto@bu.edu RI Hofmann, Stefan/B-8769-2014; OI Hofmann, Stefan/0000-0002-3548-9681; Gueorguieva, Ralitza/0000-0003-0944-5973 FU NIH; Pfizer; Janssen; Edgemont Pharmaceuticals; Clintara; Otsuka Pharmaceutical; NIH/NCCIH [R01AT007257]; NIH/NIMH [R01MH099021, R34MH099311, R34MH086668, R21MH102646, R21MH101567, K23MH100259]; Department of the Army; American Foundation for Suicide Prevention; Department of Defense; Highland Street Foundation; Palo Alto Health Sciences, Inc. FX Dr. Otto reports serving, in the last 3 years, as a paid consultant for MicroTransponder Inc., Concert Pharmaceuticals, and ProPhase, providing expert consensus opinion for Otsuka Pharmaceuticals, receiving royalty support for use of the SIGH-A from ProPhase, receiving book royalties from Oxford University Press, Routledge, and Springer, and receiving research support for other projects from NIH.; Dr. Dowd reports receiving research funding from Pfizer, Janssen and Edgemont Pharmaceuticals and serves as a paid consultant with Clintara and Otsuka Pharmaceutical.; Dr. Hofmann receives support from NIH/NCCIH (R01AT007257), NIH/NIMH (R01MH099021, R34MH099311, R34MH086668, R21MH102646, R21MH101567, K23MH100259), and the Department of the Army for work unrelated to the studies reported in this article. He receives compensation for his work as an advisor from the Palo Alto Health Sciences and Otsuka America Pharmaceutical, Inc., and for his work as a Subject Matter Expert from John Wiley & Sons, Inc. and SilverCloud Health, Inc. He also receives royalties and payments for his editorial work from various publishers.; Dr. Simon reports research grants from the American Foundation for Suicide Prevention, Department of Defense, Highland Street Foundation, and NIH; speaking/CME/consulting from the MGH Psychiatry Academy and Pfizer Pharmaceuticals, and spousal equity from G Zero and Gatekeeper.; Dr. Tolin reports receiving research funding from Palo Alto Health Sciences, Inc. NR 39 TC 1 Z9 1 U1 13 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD AUG PY 2016 VL 33 IS 8 BP 737 EP 745 DI 10.1002/da.22531 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA DW5TH UT WOS:000383709300008 PM 27315514 ER PT J AU Harris, JR AF Harris, Jay R. TI Treatment of Regional Lymph Nodes in Breast Cancer-Not Recommended for All Patients With 1 to 3 Positive Auxiliary Nodes SO JAMA ONCOLOGY LA English DT Editorial Material ID SENTINEL NODE; RADIOTHERAPY; IRRADIATION; SURGERY; TRIAL; WOMEN C1 [Harris, Jay R.] Harvard Med Sch, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 450 Brookline Ave,YC 1473, Boston, MA 02215 USA. RP Harris, JR (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 450 Brookline Ave,YC 1473, Boston, MA 02215 USA. EM jharris@lroc.harvard.edu NR 5 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD AUG PY 2016 VL 2 IS 8 BP 991 EP 992 DI 10.1001/jamaoncol.2016.0222 PG 2 WC Oncology SC Oncology GA DW5RN UT WOS:000383704700002 PM 27253737 ER PT J AU Bukowski, A Chavarri-Guerra, Y Goss, PE AF Bukowski, Alexandra Chavarri-Guerra, Yanin Goss, Paul E. TI The Potential Role of Patient Navigation in Low- and Middle-Income Countries for Patients With Cancer SO JAMA ONCOLOGY LA English DT Editorial Material ID DIAGNOSTIC RESOLUTION; IMPACT C1 [Bukowski, Alexandra; Chavarri-Guerra, Yanin; Goss, Paul E.] Global Canc Inst, Boston, MA USA. [Bukowski, Alexandra; Goss, Paul E.] Massachusetts Gen Hosp, Ctr Canc, Avon Int Breast Canc Program, 55 Fruit St,Lawrence House,Room 302, Boston, MA 02114 USA. [Goss, Paul E.] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Hematol & Oncol, Mexico City, DF, Mexico. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, Avon Int Breast Canc Program, 55 Fruit St,Lawrence House,Room 302, Boston, MA 02114 USA. EM pgoss@partners.org NR 7 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 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD AUG PY 2016 VL 2 IS 8 BP 994 EP 995 DI 10.1001/jamaoncol.2016.0766 PG 2 WC Oncology SC Oncology GA DW5RN UT WOS:000383704700004 PM 27228333 ER PT J AU Nikiforov, YE Seethala, RR Tallini, G Baloch, ZW Basolo, F Thompson, LDR Barletta, JA Wenig, BM Al Ghuzlan, A Kakudo, K Giordano, TJ Alves, VA Khanafshar, E Asa, SL El-Naggar, AK Gooding, WE Hodak, SP Lloyd, RV Maytal, G Mete, O Nikiforova, MN Nose, V Papotti, M Poller, DN Sadow, PM Tischler, AS Tuttle, M Wall, KB LiVolsi, VA Randolph, GW Ghossein, RA AF Nikiforov, Yuri E. Seethala, Raja R. Tallini, Giovanni Baloch, Zubair W. Basolo, Fulvio Thompson, Lester D. R. Barletta, Justine A. Wenig, Bruce M. Al Ghuzlan, Abir Kakudo, Kennichi Giordano, Thomas J. Alves, Venancio A. Khanafshar, Elham Asa, Sylvia L. El-Naggar, Adel K. Gooding, William E. Hodak, Steven P. Lloyd, Ricardo V. Maytal, Guy Mete, Ozgur Nikiforova, Marina N. Nose, Vania Papotti, Mauro Poller, David N. Sadow, Peter M. Tischler, Arthur S. Tuttle, Michael Wall, Kathryn B. LiVolsi, Virginia A. Randolph, Gregory W. Ghossein, Ronald A. TI Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma A Paradigm Shift to Reduce Overtreatment of Indolent Tumors SO JAMA ONCOLOGY LA English DT Article ID UNITED-STATES; OBSERVER VARIATION; NUCLEAR FEATURES; BRAF V600E; CANCER; DIAGNOSIS; OVERDIAGNOSIS; IMPACT; NEOPLASMS; PATTERNS AB IMPORTANCE Although growing evidence points to highly indolent behavior of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), most patients with EFVPTC are treated as having conventional thyroid cancer. OBJECTIVE To evaluate clinical outcomes, refine diagnostic criteria, and develop a nomenclature that appropriately reflects the biological and clinical characteristics of EFVPTC. DESIGN, SETTING, AND PARTICIPANTS International, multidisciplinary, retrospective study of patients with thyroid nodules diagnosed as EFVPTC, including 109 patients with noninvasive EFVPTC observed for 10 to 26 years and 101 patients with invasive EFVPTC observed for 1 to 18 years. Review of digitized histologic slides collected at 13 sites in 5 countries by 24 thyroid pathologists from 7 countries. A series of teleconferences and a face-to-face conference were used to establish consensus diagnostic criteria and develop new nomenclature. MAIN OUTCOMES AND MEASURES Frequency of adverse outcomes, including death from disease, distant or locoregional metastases, and structural or biochemical recurrence, in patients with noninvasive and invasive EFVPTC diagnosed on the basis of a set of reproducible histopathologic criteria. RESULTS Consensus diagnostic criteria for EFVPTC were developed by 24 thyroid pathologists. All of the 109 patients with noninvasive EFVPTC (67 treated with only lobectomy, none received radioactive iodine ablation) were alive with no evidence of disease at final follow-up (median [range], 13 [10-26] years). An adverse event was seen in 12 of 101 (12%) of the cases of invasive EFVPTC, including 5 patients developing distant metastases, 2 of whom died of disease. Based on the outcome information for noninvasive EFVPTC, the name "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) was adopted. A simplified diagnostic nuclear scoring scheme was developed and validated, yielding a sensitivity of 98.6%(95% CI, 96.3%-99.4%), specificity of 90.1% (95% CI, 86.0%-93.1%), and overall classification accuracy of 94.3%(95% CI, 92.1%-96.0%) for NIFTP. CONCLUSIONS AND RELEVANCE Thyroid tumors currently diagnosed as noninvasive EFVPTC have a very low risk of adverse outcome and should be termed NIFTP. This reclassification will affect a large population of patients worldwide and result in a significant reduction in psychological and clinical consequences associated with the diagnosis of cancer. C1 [Nikiforov, Yuri E.; Seethala, Raja R.; Nikiforova, Marina N.] Univ Pittsburgh, Dept Pathol, 3477 Euler Way,Room 8031, Pittsburgh, PA 15213 USA. [Tallini, Giovanni] Univ Bologna, Sch Med, Dept Med DIMES, Anat Pathol, Bologna, Italy. [Baloch, Zubair W.; LiVolsi, Virginia A.] Hosp Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA USA. [Basolo, Fulvio] Univ Pisa, Dept Surg Med & Mol Pathol, Pisa, Italy. [Thompson, Lester D. R.] Southern Calif Permanente Med Grp, Woodland Hills, CA USA. [Barletta, Justine A.] Brigham & Womens Hosp, Harvard Med Sch, Dept Pathol, Boston, MA 02115 USA. [Wenig, Bruce M.] Mt Sinai Hlth Syst, Dept Pathol, New York, NY USA. [Al Ghuzlan, Abir] Dept Med Biol & Pathol, Gustave Roussy Canc Campus Grand Paris, Villejuif, France. [Kakudo, Kennichi] Kindai Univ, Fac Med, Dept Pathol & Lab Med, Ikoma City, Japan. [Giordano, Thomas J.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Giordano, Thomas J.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Alves, Venancio A.] Univ Sao Paulo, Sch Med, Dept Pathol, Sao Paulo, Brazil. [Alves, Venancio A.] Hosp Alemao Oswaldo Cruz, Dept Pathol, Sao Paulo, Brazil. [Khanafshar, Elham] Univ Calif San Francisco, Dept Pathol, San Francisco, CA USA. [Asa, Sylvia L.; Mete, Ozgur] Univ Hlth Network, Dept Pathol, Toronto, ON, Canada. [El-Naggar, Adel K.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Gooding, William E.] Univ Pittsburgh, Inst Canc, Biostat Facil, Pittsburgh, PA USA. [Hodak, Steven P.] NYU, Sch Med, Div Endocrinol & Metab, New York, NY USA. [Lloyd, Ricardo V.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Maytal, Guy] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Nose, Vania; Sadow, Peter M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Nose, Vania; Sadow, Peter M.] Harvard Med Sch, Dept Pathol, Boston, MA USA. [Papotti, Mauro] Univ Turin, Dept Oncol, Turin, Italy. [Poller, David N.] Queen Alexandra Hosp, Dept Pathol, Portsmouth, Hants, England. [Tischler, Arthur S.] Tufts Univ, Sch Med, Tufts Med Ctr, Dept Pathol & Lab Med, Boston, MA 02111 USA. [Tuttle, Michael] Mem Sloan Kettering Canc Ctr, Dept Endocrinol, New York, NY 10021 USA. [Wall, Kathryn B.] Thyroid Canc Survivors Assoc Inc, Raleigh, NC USA. [Randolph, Gregory W.] Massachusetts Eye & Ear Infirm, Gen & Thyroid & Parathyroid Endocrine Surg Div, Boston, MA 02114 USA. [Ghossein, Ronald A.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY USA. RP Nikiforov, YE (reprint author), Univ Pittsburgh, Dept Pathol, 3477 Euler Way,Room 8031, Pittsburgh, PA 15213 USA. EM nikiforovye@upmc.edu OI BASOLO, FULVIO/0000-0003-1657-5020 FU National Cancer Institute [P30CA047904]; UPCI; University of Pittsburgh Medical Center (UPMC); CBLPath, Inc (Rye Brook, NY) FX This project used the University of Pittsburgh Cancer Institute (UPCI) Biostatistics Facility that is supported in part by award P30CA047904 from the National Cancer Institute. Molecular analysis was supported in part by funds from the UPCI and University of Pittsburgh Medical Center (UPMC). The Endocrine Pathology Society conference for reevaluation of the encapsulated follicular variant of papillary thyroid carcinoma held on March 20-21 in Boston, Massachusetts, was supported by an education grant from CBLPath, Inc (Rye Brook, NY). NR 35 TC 35 Z9 35 U1 556 U2 556 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD AUG PY 2016 VL 2 IS 8 BP 1023 EP 1029 DI 10.1001/jamaoncol.2016.0386 PG 7 WC Oncology SC Oncology GA DW5RN UT WOS:000383704700011 PM 27078145 ER PT J AU Chen, G McQuade, JL Panka, DJ Hudgens, CW Amin-Mansour, A Mu, XJ Bahl, S Jane-Valbuena, J Wani, KM Reuben, A Creasy, CA Jiang, H Cooper, ZA Roszik, J Bassett, RL Joon, AY Simpson, LM Mouton, RD Glitza, IC Patel, SP Hwu, WJ Amaria, RN Diab, A Hwu, P Lazar, AJ Wargo, JA Garraway, LA Tetzlaff, MT Sullivan, RJ Kim, KB Davies, MA AF Chen, Guo McQuade, Jennifer L. Panka, David J. Hudgens, Courtney W. Amin-Mansour, Ali Mu, Xinmeng Jasmine Bahl, Samira Jane-Valbuena, Judit Wani, Khalida M. Reuben, Alexandre Creasy, Caitlyn A. Jiang, Hong Cooper, Zachary A. Roszik, Jason Bassett, Roland L., Jr. Joon, Aron Y. Simpson, Lauren M. Mouton, Rosalind D. Glitza, Isabella C. Patel, Sapna P. Hwu, Wen-Jen Amaria, Rodabe N. Diab, Adi Hwu, Patrick Lazar, Alexander J. Wargo, Jennifer A. Garraway, Levi A. Tetzlaff, Michael T. Sullivan, Ryan J. Kim, Kevin B. Davies, Michael A. TI Clinical, Molecular, and Immune Analysis of Dabrafenib-Trametinib Combination Treatment for BRAF Inhibitor-Refractory Metastatic Melanoma A Phase 2 Clinical Trial SO JAMA ONCOLOGY LA English DT Article ID ACQUIRED-RESISTANCE; MEK INHIBITION; RAF INHIBITION; SOLID TUMORS; MUTATIONS; PATHWAY; BRAF(V600E); VEMURAFENIB; THERAPY; CANCER AB IMPORTANCE Combined treatment with dabrafenib and trametinib (CombiDT) achieves clinical responses in only about 15% of patients with BRAF inhibitor (BRAFi)-refractory metastatic melanoma in contrast to the higher response rate observed in BRAFi-naive patients. Identifying correlates of response and mechanisms of resistance in this population will facilitate clinical management and rational therapeutic development. OBJECTIVE To determine correlates of benefit from CombiDT therapy in patients with BRAFi-refractory metastatic melanoma. DESIGN, SETTING, AND PARTICIPANTS Single-center, single-arm, open-label phase 2 trial of CombiDT treatment in patients with BRAF V600 metastatic melanoma resistant to BRAFi monotherapy conducted between September 2012 and October 2014 at the University of Texas MD Anderson Cancer Center. Key eligibility criteria for participants included BRAF V600 metastatic melanoma, prior BRAFi monotherapy, measurable disease (RECIST 1.1), and tumor accessible for biopsy. INTERVENTIONS Patients were treated with dabrafenib (150mg, twice daily) and trametinib (2mg/d) continuously until disease progression or intolerance. All participants underwent a mandatory baseline biopsy, and optional biopsy specimens were obtained on treatment and at disease progression. Whole-exome sequencing, reverse transcription polymerase chain reaction analysis for BRAF splicing, RNA sequencing, and immunohistochemical analysis were performed on tumor samples, and blood was analyzed for levels of circulating BRAF V600. MAIN OUTCOMES AND MEASURES The primary end point was overall response rate (ORR). Progression-free survival (PFS) and overall survival (OS) were secondary clinical end points. RESULTS A total of 28 patients were screened, and 23 enrolled. Among evaluable patients, the confirmed ORR was 10%; disease control rate (DCR) was 45%, and median PFS was 13 weeks. Clinical benefit was associated with duration of prior BRAFi therapy greater than 6 months (DCR, 73% vs 11% for <= 6 months; P=.02) and decrease in circulating BRAF V600 at day 8 of cycle 1 (DCR, 75% vs 18% for no decrease; P=.02) but not with pretreatment mitogen-activated protein kinase (MAPK) pathway mutations or activation. Biopsy specimens obtained during treatment demonstrated that CombiDT therapy failed to achieve significant MAPK pathway inhibition or immune infiltration in most patients. CONCLUSIONS AND RELEVANCE The baseline presence of MAPK pathway alterations was not associated with benefit from CombiDT in patients with BRAFi-refractory metastatic melanoma. Failure to inhibit the MAPK pathway provides a likely explanation for the limited clinical benefit of CombiDT in this setting. Circulating BRAF V600 is a promising early biomarker of clinical response. C1 [Chen, Guo; Creasy, Caitlyn A.; Roszik, Jason; Simpson, Lauren M.; Mouton, Rosalind D.; Glitza, Isabella C.; Patel, Sapna P.; Hwu, Wen-Jen; Amaria, Rodabe N.; Diab, Adi; Hwu, Patrick; Davies, Michael A.] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA. [McQuade, Jennifer L.] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Houston, TX 77030 USA. [Panka, David J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Hudgens, Courtney W.; Wani, Khalida M.; Lazar, Alexander J.; Tetzlaff, Michael T.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Hudgens, Courtney W.; Wani, Khalida M.; Lazar, Alexander J.; Tetzlaff, Michael T.] Univ Texas MD Anderson Canc Ctr, Dept Translat & Mol Pathol, Houston, TX 77030 USA. [Amin-Mansour, Ali; Mu, Xinmeng Jasmine; Bahl, Samira; Jane-Valbuena, Judit; Garraway, Levi A.] Broad Inst, Cambridge, MA USA. [Reuben, Alexandre; Jiang, Hong; Cooper, Zachary A.; Wargo, Jennifer A.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Reuben, Alexandre; Jiang, Hong; Cooper, Zachary A.; Wargo, Jennifer A.] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA. [Bassett, Roland L., Jr.; Joon, Aron Y.] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. [Sullivan, Ryan J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kim, Kevin B.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Davies, Michael A.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA. RP Davies, MA (reprint author), Univ Texas MD Anderson Canc Ctr, 1515 Holcombe,Unit 0430, Houston, TX 77030 USA. EM mdavies@mdanderson.org FU Cancer Prevention and Research Institute of Texas [RP120505, 1R01CA187076-01, 5R01CA154710-03, P50 CA093459, P30 CA016672]; Dr Miriam and Sheldon G. Adelson Medical Research Foundation; University of Texas MD Anderson Cancer Center Melanoma Moon Shots Program; ASCO Young Investigator Award; T32 Institutional Training Grant [T32 CA009666]; NIH [1K08CA160692-01A1]; Melanoma Research Alliance Team Science Award; Kennedy Memorial Foundation [0727030] FX This work was supported by the Cancer Prevention and Research Institute of Texas (RP120505, 1R01CA187076-01, 5R01CA154710-03, P50 CA093459, and P30 CA016672), the Dr Miriam and Sheldon G. Adelson Medical Research Foundation, and the University of Texas MD Anderson Cancer Center Melanoma Moon Shots Program. Dr McQuade is supported by an ASCO Young Investigator Award and a T32 Institutional Training Grant (T32 CA009666). Dr Wargo acknowledges NIH grants 1K08CA160692-01A1, the Melanoma Research Alliance Team Science Award, and the Kennedy Memorial Foundation grant # 0727030. NR 33 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD AUG PY 2016 VL 2 IS 8 BP 1056 EP 1064 DI 10.1001/jamaoncol.2016.0509 PG 9 WC Oncology SC Oncology GA DW5RN UT WOS:000383704700017 PM 27124486 ER PT J AU Liu, D Plimack, ER Hoffman-Censits, J Garraway, LA Bellmunt, J Van Allen, E Rosenberg, JE AF Liu, David Plimack, Elizabeth R. Hoffman-Censits, Jean Garraway, Levi A. Bellmunt, Joaquim Van Allen, Eliezer Rosenberg, Jonathan E. TI Clinical Validation of Chemotherapy Response Biomarker ERCC2 in Muscle-Invasive Urothelial Bladder Carcinoma SO JAMA ONCOLOGY LA English DT Letter ID CISPLATIN SENSITIVITY; REPAIR C1 [Liu, David; Garraway, Levi A.; Bellmunt, Joaquim; Van Allen, Eliezer] Dana Farber Canc Inst, Boston, MA 02115 USA. [Garraway, Levi A.; Van Allen, Eliezer] Broad Inst Harvard & MIT, Cambridge, MA USA. [Hoffman-Censits, Jean] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. [Rosenberg, Jonathan E.] Mem Sloan Kettering Canc Ctr, New York, NY USA. RP Rosenberg, JE (reprint author), Mem Sloan Kettering Canc Ctr, Sidney Kimmel Ctr Prostate & Urol Canc, 353 E 68th St, New York, NY 10065 USA. EM rosenbj1@mskcc.org NR 5 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 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD AUG PY 2016 VL 2 IS 8 BP 1094 EP 1096 DI 10.1001/jamaoncol.2016.1056 PG 4 WC Oncology SC Oncology GA DW5RN UT WOS:000383704700025 PM 27310333 ER PT J AU Sacher, AG Alden, RS Oxnard, GR AF Sacher, Adrian G. Alden, Ryan S. Oxnard, Geoffrey R. TI Early Intervention in Lung Cancers With Rapid Plasma Genotyping for EGFR and KRAS Mutations Reply SO JAMA ONCOLOGY LA English DT Letter C1 [Sacher, Adrian G.; Alden, Ryan S.; Oxnard, Geoffrey R.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 450 Brookline Ave, Boston, MA 02115 USA. [Sacher, Adrian G.; Oxnard, Geoffrey R.] Brigham & Womens Hosp, Harvard Med Sch, 75 Francis St, Boston, MA 02115 USA. [Sacher, Adrian G.] Columbia Univ, New York Presbyterian Hosp, New York, NY USA. RP Oxnard, GR (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM geoffrey_oxnard@dfci.harvard.edu NR 3 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 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD AUG PY 2016 VL 2 IS 8 BP 1096 EP 1097 DI 10.1001/jamaoncol.2016.1963 PG 3 WC Oncology SC Oncology GA DW5RN UT WOS:000383704700027 PM 27388452 ER PT J AU Goldstone, RN McCormack, MC Khan, SI Salinas, HM Meppelink, A Randolph, MA Watkins, MT Redmond, RW Austen, WG AF Goldstone, Robert N. McCormack, Michael C. Khan, Saiqa I. Salinas, Harry M. Meppelink, Amanda Randolph, Mark A. Watkins, Michael T. Redmond, Robert W. Austen, William G., Jr. TI Photochemical Tissue Passivation Reduces Vein Graft Intimal Hyperplasia in a Swine Model of Arteriovenous Bypass Grafting SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE cardiovascular disease; collagen; hyperplasia; intima-media thickness; vein graft ID SMOOTH-MUSCLE-CELLS; SAPHENOUS-VEIN; GROWTH-FACTOR; PIG MODEL; DISEASE; REVASCULARIZATION; PATHOPHYSIOLOGY; ASSOCIATION; MECHANISMS; STRATEGIES AB Background-Bypass grafting remains the standard of care for coronary artery disease and severe lower extremity ischemia. Efficacy is limited by poor long-term venous graft patency secondary to intimal hyperplasia (IH) caused by venous injury upon exposure to arterial pressure. We investigate whether photochemical tissue passivation (PTP) treatment of vein grafts modulates smooth muscle cell (SMC) proliferation and migration, and inhibits development of IH. Methods and Results-PTP was performed at increasing fluences up to 120 J/cm(2) on porcine veins. Tensiometry performed to assess vessel elasticity/stiffness showed increased stiffness with increasing fluence until plateauing at 90 J/cm(2) (median, interquartile range [IQR]). At 90 J/cm(2), PTP-treated vessels had a 10-fold greater Young's modulus than untreated controls (954 [IQR, 2217] vs 99 kPa [IQR, 63]; P= 0.03). Each pig received a PTP-treated and untreated carotid artery venous interposition graft. At 4-weeks, intimal/medial areas were assessed. PTP reduced the degree of IH by 66% and medial hypertrophy by 49%. Intimal area was 3.91 (IQR, 1.2) and 1.3 mm(2) (IQR, 0.97; P <= 0.001) in untreated and PTP-treated grafts, respectively. Medial area was 9.2 (IQR, 3.2) and 4.7 mm(2) (IQR, 2.0; P <= 0.001) in untreated and PTP-treated grafts, respectively. Immunohistochemistry was performed to assess alpha-smooth muscle actin (SMA) and proliferating cell nuclear antigen (PCNA). Objectively, there were less SMA-positive cells within the intima/media of PTP-treated vessels than controls. There was an increase in PCNA-positive cells within control vein grafts (18% [IQR, 5.3]) versus PTP-treated vein grafts (5% [IQR, 0.9]; P= 0.02). Conclusions-By strengthening vein grafts, PTP decreases SMC proliferation and migration, thereby reducing IH. C1 [Goldstone, Robert N.; McCormack, Michael C.; Khan, Saiqa I.; Salinas, Harry M.; Meppelink, Amanda; Randolph, Mark A.; Austen, William G., Jr.] Harvard Med Sch, Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA USA. [Watkins, Michael T.] Harvard Med Sch, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA USA. [Redmond, Robert W.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA USA. [Redmond, Robert W.] Harvard Med Sch, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA. RP Austen, WG (reprint author), Massachusetts Gen Hosp, Div Plast & Reconstruct Surg & Burn Surg, 15 Parkman St,WAC 435, Boston, MA 02114 USA. EM wausten@partners.org FU American College of Surgeons Resident Research Scholarship; Partners HealthCare Innovation Development Grant FX This project was funded by the American College of Surgeons Resident Research Scholarship and a Partners HealthCare Innovation Development Grant. NR 29 TC 0 Z9 0 U1 0 U2 0 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 AUG PY 2016 VL 5 IS 8 AR e003856 DI 10.1161/JAHA.116.003856 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA EA6DE UT WOS:000386714900037 ER PT J AU Karacsonyi, J Alaswad, K Jaffer, FA Yeh, RW Patel, M Bahadorani, J Karatasakis, A Danek, BA Doing, A Grantham, JA Karmpaliotis, D Moses, JW Kirtane, A Parikh, M Ali, Z Lombardi, WL Kandzari, DE Lembo, N Garcia, S Wyman, MR Alame, A Nguyen-Trong, PKJ Resendes, E Kalsaria, P Rangan, BV Ungi, I Thompson, CA Banerjee, S Brilakis, ES AF Karacsonyi, Judit Alaswad, Khaldoon Jaffer, Farouc A. Yeh, Robert W. Patel, Mitul Bahadorani, John Karatasakis, Aris Danek, Barbara A. Doing, Anthony Grantham, J. Aaron Karmpaliotis, Dimitri Moses, Jeffrey W. Kirtane, Ajay Parikh, Manish Ali, Ziad Lombardi, William L. Kandzari, David E. Lembo, Nicholas Garcia, Santiago Wyman, Michael R. Alame, Aya Nguyen-Trong, Phuong-Khanh J. Resendes, Erica Kalsaria, Pratik Rangan, Bavana V. Ungi, Imre Thompson, Craig A. Banerjee, Subhash Brilakis, Emmanouil S. TI Use of Intravascular Imaging During Chronic Total Occlusion Percutaneous Coronary Intervention: Insights From a Contemporary Multicenter Registry SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE chronic total occlusion; intravascular ultrasound; optical coherence tomography; percutaneous coronary intervention ID OPTICAL COHERENCE TOMOGRAPHY; REVERSE CONTROLLED ANTEGRADE; ELUTING STENT IMPLANTATION; IN-HOSPITAL OUTCOMES; HYBRID APPROACH; RETROGRADE TRACKING; ULTRASOUND GUIDANCE; PROCEDURAL OUTCOMES; CTO REGISTRY; RECANALIZATION AB Background-Intravascular imaging can facilitate chronic total occlusion (CTO) percutaneous coronary intervention. Methods and Results-We examined the frequency of use and outcomes of intravascular imaging among 619 CTO percutaneous coronary interventions performed between 2012 and 2015 at 7 US centers. Mean age was 65.4 +/- 10 years and 85% of the patients were men. Intravascular imaging was used in 38%: intravascular ultrasound in 36%, optical coherence tomography in 3%, and both in 1.45%. Intravascular imaging was used for stent sizing (26.3%), stent optimization (38.0%), and CTO crossing (35.7%, antegrade in 27.9%, and retrograde in 7.8%). Intravascular imaging to facilitate crossing was used more frequently in lesions with proximal cap ambiguity (49% versus 26%, P<0.0001) and with retrograde as compared with antegrade-only cases (67% versus 31%, P<0.0001). Despite higher complexity (Japanese CTO score: 2.86 +/- 1.19 versus 2.43 +/- 1.19, P=0.001), cases in which imaging was used for crossing had similar technical and procedural success (92.8% versus 89.6%, P=0.302 and 90.1% versus 88.3%, P=0.588, respectively) and similar incidence of major cardiac adverse events (2.7% versus 3.2%, P=0.772). Use of intravascular imaging was associated with longer procedure (192 minutes [interquartile range 130, 255] versus 131 minutes [90, 192], P<0.0001) and fluoroscopy (71 minutes [44, 93] versus 39 minutes [25, 69], P<0.0001) time. Conclusions-Intravascular imaging is frequently performed during CTO percutaneous coronary intervention both for crossing and for stent selection/optimization. Despite its use in more complex lesion subsets, intravascular imaging was associated with similar rates of technical and procedural success for CTO percutaneous coronary intervention. C1 [Karacsonyi, Judit; Karatasakis, Aris; Danek, Barbara A.; Alame, Aya; Nguyen-Trong, Phuong-Khanh J.; Resendes, Erica; Kalsaria, Pratik; Rangan, Bavana V.; Banerjee, Subhash; Brilakis, Emmanouil S.] VA North Texas Healthcare Syst, Dallas, TX USA. [Karacsonyi, Judit; Karatasakis, Aris; Danek, Barbara A.; Alame, Aya; Nguyen-Trong, Phuong-Khanh J.; Resendes, Erica; Rangan, Bavana V.; Banerjee, Subhash; Brilakis, Emmanouil S.] UT Southwestern Med Ctr, Dallas, TX USA. [Karacsonyi, Judit; Ungi, Imre] Univ Szeged, Dept Internal Med 2, Div Invas Cardiol, Szeged, Hungary. [Karacsonyi, Judit; Ungi, Imre] Univ Szeged, Ctr Cardiol, Szeged, Hungary. [Alaswad, Khaldoon] Henry Ford Hosp, Detroit, MI 48202 USA. [Jaffer, Farouc A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jaffer, Farouc A.] Harvard Med Sch, Boston, MA USA. [Yeh, Robert W.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Patel, Mitul; Bahadorani, John] VA San Diego Healthcare Syst, San Diego, CA USA. [Patel, Mitul; Bahadorani, John] Univ Calif San Diego, San Diego, CA 92103 USA. [Doing, Anthony] Med Ctr Rockies, Loveland, CO USA. [Grantham, J. Aaron] Mid Amer Heart Inst, Kansas City, MO USA. [Karmpaliotis, Dimitri; Moses, Jeffrey W.; Kirtane, Ajay; Parikh, Manish; Ali, Ziad] Columbia Univ, New York, NY USA. [Lombardi, William L.] Univ Washington, Seattle, WA 98195 USA. [Kandzari, David E.; Lembo, Nicholas] Piedmont Heart Inst, Atlanta, GA USA. [Garcia, Santiago] Minneapolis VA Healthcare Syst, Minneapolis, MN USA. [Garcia, Santiago] Univ Minnesota, Minneapolis, MN USA. [Wyman, Michael R.] Torrance Mem Med Ctr, Torrance, CA USA. [Thompson, Craig A.] Boston Sci, Natick, MA USA. RP Brilakis, ES (reprint author), Dallas VA Med Ctr 111A, 4500 South Lancaster Rd, Dallas, TX 75216 USA. EM esbrilakis@gmail.com OI Parikh, Manish/0000-0002-8612-5407 FU Clinical and Translational Science Awards National Institutes of Health Grant [UL1-RR024982] FX This was work was supported by Clinical and Translational Science Awards National Institutes of Health Grant UL1-RR024982. NR 38 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD AUG PY 2016 VL 5 IS 8 AR e003890 DI 10.1161/JAHA.116.003890 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA EA6DE UT WOS:000386714900039 ER PT J AU Madenci, AL Stetson, A Weldon, CB Lehmann, LE AF Madenci, Arin L. Stetson, Alyssa Weldon, Christopher B. Lehmann, Leslie E. TI Safety of peritoneal and pleural drain placement in pediatric stem cell transplant recipients with severe veno-occlusive disease SO PEDIATRIC TRANSPLANTATION LA English DT Article DE hematopoietic stem cell transplantation; pediatric; veno-occlusive disease; sinusoidal obstruction syndrome; peritoneal drain; pleural drain ID BONE-MARROW-TRANSPLANTATION; INTENSIVE-CARE UNIT; OPERATING-ROOM; RISK-FACTORS; CHILDREN; LIVER; COMPLICATIONS; DEFIBROTIDE; MORTALITY; SURVIVAL AB Hepatic VOD (veno-occlusive disease) is a serious complication of HSCT (hematopoietic stem cell transplantation) and has historically been associated with high mortality. This obstruction to hepatic flow often results in fluid collections in the peritoneal and pleural cavities. Catheter placement to drain ascites or pleural fluid may reduce intra-abdominal hypertension and/or improve respiratory parameters. The safety of these interventions among critically ill, immunocompromised children is unknown. Among 32 HSCT recipients (2000-2012) with severe VOD, we assessed the primary outcome of procedural complication from peritoneal drain placement. Twenty-four (75%) patients underwent peritoneal drain placement. No patient sustained visceral perforation or hemorrhage with drain placement. Overall mortality was 47% (n = 15). The procedure was not associated with increased overall mortality (p > 0.99). Eight (25%) peritoneal drains required replacement for malfunction. Of 24 patients with peritoneal drains, one (4%) patient had a positive culture from ascitic fluid. Eight (25%) patients underwent pleural drain placement. No pleural drain-related procedural complication or infection occurred. Four (50%) of the eight patients with pleural drains had de-escalation in oxygen requirement at drain removal, compared to time of placement. In this study, peritoneal and pleural drains were safe interventions for children with severe VOD. C1 [Madenci, Arin L.; Weldon, Christopher B.] Boston Childrens Hosp, Dept Surg, Boston, MA USA. [Madenci, Arin L.; Weldon, Christopher B.; Lehmann, Leslie E.] Harvard Med Sch, Boston, MA USA. [Madenci, Arin L.] Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. [Stetson, Alyssa; Weldon, Christopher B.; Lehmann, Leslie E.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Lehmann, Leslie E.] Boston Childrens Hosp, Dept Med, Div Hematol Oncol, Boston, MA USA. RP Lehmann, LE (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM leslie_lehmann@dfci.harvard.edu OI Madenci, Arin/0000-0003-1258-7278 NR 24 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1397-3142 EI 1399-3046 J9 PEDIATR TRANSPLANT JI Pediatr. Transplant. PD AUG PY 2016 VL 20 IS 5 BP 687 EP 691 DI 10.1111/petr.12730 PG 5 WC Pediatrics; Transplantation SC Pediatrics; Transplantation GA DW4CS UT WOS:000383590300014 PM 27373552 ER PT J AU Castillo, JJ Palomba, ML Advani, R Treon, SP AF Castillo, Jorge J. Palomba, M. Lia Advani, Ranjana Treon, Steven P. TI Ibrutinib in Waldenstrom macroglobulinemia: latest evidence and clinical experience SO THERAPEUTIC ADVANCES IN HEMATOLOGY LA English DT Review DE Bruton's tyrosine kinase; ibrutinib; lymphoplasmacytic lymphoma; Waldenstrom macroglobulinemia ID CHRONIC LYMPHOCYTIC-LEUKEMIA; BRUTON TYROSINE KINASE; MANTLE-CELL LYMPHOMA; END RESULTS DATABASE; ATRIAL-FIBRILLATION; INNATE IMMUNITY; PRIMARY THERAPY; WHIM-SYNDROME; RITUXIMAB; DEXAMETHASONE AB Ibrutinib is an oral Bruton's tyrosine kinase (BTK) inhibitor, which has recently gained approval by the United States (US) Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of patients with symptomatic Waldenstrom macroglobulinemia (WM). Herein, we review the role of BTK in the pathophysiology of WM, and present the results of the preclinical and clinical studies that led to the initial investigation and later approval of ibrutinib in WM. We also discuss aspects associated with ibrutinib therapy in WM patients, especially focusing on genomic profiling and the impact on response to ibrutinib, and the management of adverse events. C1 [Castillo, Jorge J.] Harvard Med Sch, Dana Farber Canc Inst, Bing Ctr Waldenstrom Macroglobulinemia, 450 Brookline Ave, Boston, MA 02115 USA. [Palomba, M. Lia] Mem Sloan Kettering Canc Ctr, Div Hematol, 1275 York Ave, New York, NY 10021 USA. [Advani, Ranjana] Stanford Univ, Med Ctr, Div Oncol, Stanford, CA USA. [Treon, Steven P.] Harvard Med Sch, Dana Farber Canc Inst, Bing Ctr Waldenstrom Macroglobulinemia, Boston, MA USA. RP Castillo, JJ (reprint author), Harvard Med Sch, Dana Farber Canc Inst, Bing Ctr Waldenstrom Macroglobulinemia, 450 Brookline Ave, Boston, MA 02115 USA. EM Jorgej_castillo@dfci.harvard.edu NR 49 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 2040-6207 EI 2040-6215 J9 THER ADV HEMATOL JI Ther. Adv. Hematol. PD AUG PY 2016 VL 7 IS 4 BP 179 EP 186 DI 10.1177/2040620716654102 PG 8 WC Hematology SC Hematology GA DW5AF UT WOS:000383653400001 PM 27493708 ER PT J AU Arora, M Gowda, S Tuscano, J AF Arora, Mili Gowda, Sonia Tuscano, Joseph TI A comprehensive review of lenalidomide in B-cell non-Hodgkin lymphoma SO THERAPEUTIC ADVANCES IN HEMATOLOGY LA English DT Review DE lenalidomide; non-Hodgkin lymphoma; rituximab ID SINGLE-AGENT LENALIDOMIDE; PHASE-II; PLUS RITUXIMAB; PROGNOSTIC-FACTORS; OPEN-LABEL; TRIAL; MULTICENTER; INDOLENT; THERAPY; DEXAMETHASONE AB Lenalidomide, an immunomodulatory drug that the US Food and Drug Administration (FDA) approved for the treatment of multiple myeloma, 5q-myelodysplasia and mantle-cell lymphoma (MCL), has encouraging efficacy in other B-cell malignancies. Its unique mechanism of action is in part due to altering the tumor microenvironment and potentiating the activity of T and natural-killer (NK) cells. Impressive clinical activity and excellent tolerability allows broad applicability. Lenalidomide has been used in a wide range of B-cell malignancies for years, but in 2013, the FDA marked its approval as a single agent only in relapsed/refractory mantle-cell lymphoma. Perhaps most impressive is the efficacy of lenalidomide when combined with monoclonal antibodies. Impressive efficacy and toxicity profiles with the combination of lenalidomide and rituximab in B-cell lymphomas in both the upfront and relapsed/refractory setting may allow a shift in our current treatment paradigm in both indolent and aggressive non-Hodgkin lymphoma (NHL). This review will summarize the current data in the relapsed/refractory and front-line setting of NHL with single-agent lenalidomide as well as its use in combination with other agents. C1 [Tuscano, Joseph] UC Davis Med Ctr, Northern Carolina Healthcare Syst, Div Hematol & Oncol, Dept Internal Med,Dept Vet Affairs, 4501 X St, Sacramento, CA 95817 USA. [Arora, Mili; Gowda, Sonia] Dept Internal Med, Div Hematol & Oncol, Sacramento, CA USA. [Arora, Mili] US Dept Vet Affairs, Northern Carolina Healthcare Syst, Sacramento, CA USA. RP Tuscano, J (reprint author), UC Davis Med Ctr, Northern Carolina Healthcare Syst, Div Hematol & Oncol, Dept Internal Med,Dept Vet Affairs, 4501 X St, Sacramento, CA 95817 USA. EM joseph.tuscano@ucdmc.ucdavis.edu NR 51 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 2040-6207 EI 2040-6215 J9 THER ADV HEMATOL JI Ther. Adv. Hematol. PD AUG PY 2016 VL 7 IS 4 BP 209 EP 221 DI 10.1177/2040620716652861 PG 13 WC Hematology SC Hematology GA DW5AF UT WOS:000383653400004 PM 27493711 ER PT J AU Ohye, B Kelly, H Chen, Y Zakarian, RJ Simon, NM Bui, E AF Ohye, Bonnie Kelly, Hope Chen, Yang Zakarian, Rebecca J. Simon, Naomi M. Bui, Eric TI Staying Strong With Schools: A Civilian School-Based Intervention to Promote Resilience for Military-Connected Children SO MILITARY MEDICINE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; FACING WARTIME DEPLOYMENTS; FAMILY-CENTERED PREVENTION; COMMUNITIES; SUPPORT; IMPACT AB Since September 11, 2001, over 2 million U.S. service members have been deployed to Iraq or Afghanistan, resulting in hundreds of thousands of military-connected children (MCC) having experienced a parental deployment. Although parental deployments have significantly burdened these children, few evidence-based interventions designed to support their resilience to these stressors are available. To address this gap, we developed a civilian school-based intervention to promote resilience in MCC living in the community. Our intervention, Staying Strong With Schools (SSWS), aims to deliver: a training to all school professionals early in the school year to educate them about challenges for children and families experiencing parental deployment and signs of deployment-related distress; and a year-long training for the school guidance counselor who coordinates communication and provides psychosocial support to MCC within the school community. We piloted SSWS in two civilian elementary schools and found promising feasibility and acceptability. C1 [Ohye, Bonnie; Kelly, Hope; Chen, Yang; Zakarian, Rebecca J.; Simon, Naomi M.; Bui, Eric] Red Sox Fdn, One Bowdoin Sq,Suite 650, Boston, MA 02114 USA. [Ohye, Bonnie; Kelly, Hope; Chen, Yang; Zakarian, Rebecca J.; Simon, Naomi M.; Bui, Eric] Massachusetts Gen Hosp, Home Base Program, One Bowdoin Sq,Suite 650, Boston, MA 02114 USA. [Ohye, Bonnie; Simon, Naomi M.; Bui, Eric] Harvard Med Sch, 25 Shattuck St, Boston, MA 02115 USA. RP Ohye, B (reprint author), Red Sox Fdn, One Bowdoin Sq,Suite 650, Boston, MA 02114 USA.; Ohye, B (reprint author), Massachusetts Gen Hosp, Home Base Program, One Bowdoin Sq,Suite 650, Boston, MA 02114 USA.; Ohye, B (reprint author), Harvard Med Sch, 25 Shattuck St, Boston, MA 02115 USA. NR 28 TC 0 Z9 0 U1 0 U2 0 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 EI 1930-613X J9 MIL MED JI Milit. Med. PD AUG PY 2016 VL 181 IS 8 BP 872 EP 877 DI 10.7205/MILMED-D-15-00234 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA DW5MI UT WOS:000383688900033 PM 27483526 ER PT J AU Pasquina, PF Isaacson, BM Johnson, E Rhoades, DS Lindholm, MP Grindle, GG Cooper, RA AF Pasquina, Paul F. Isaacson, Brad M. Johnson, Elizabeth Rhoades, Daniel S. Lindholm, Mark P. Grindle, Garrett G. Cooper, Rory A. TI A Patient-Controlled Analgesia Adaptor to Mitigate Postsurgical Pain for Combat Casualties With Multiple Limb Amputation: A Case Series SO MILITARY MEDICINE LA English DT Article ID REHABILITATION AB The use of explosive armaments during Operation Iraqi Freedom, Operation Enduring Freedom, and Operation New Dawn has resulted in a significant number of injured U.S. service members. These weapons often generate substantial extremity trauma requiring multiple surgical procedures to preserve life, limb, and restore function. For those individuals who require multiple surgeries, the use of patient-controlled analgesia (PCA) devices can be an effective way to achieve adequate pain management and promote successful rehabilitation and recovery during inpatient treatment. A subpopulation of patients are unable to independently control a PCA device because of severe multiple limb dysfunction and/or loss. In response to the needs of these patients, our team designed and developed a custom adaptor to assist service members who would otherwise not be able to use a PCA. Patient feedback of the device indicated a positive response, improved independence, and overall satisfaction during inpatient hospitalization. C1 [Pasquina, Paul F.; Isaacson, Brad M.; Johnson, Elizabeth; Rhoades, Daniel S.; Lindholm, Mark P.] Uniformed Serv Univ Hlth Sci, Ctr Rehabil Sci Res, Dept Phys Med & Rehabil, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. [Pasquina, Paul F.; Isaacson, Brad M.; Rhoades, Daniel S.; Lindholm, Mark P.] Walter Reed Natl Mil Med Ctr, Dept Rehabil, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. [Isaacson, Brad M.; Johnson, Elizabeth] Henry M Jackson Fdn Adv Mil Med, 6720A Rockledge Dr,100, Bethesda, MD 20817 USA. [Grindle, Garrett G.; Cooper, Rory A.] Univ Pittsburgh, US Dept Vet Affairs, Human Engn Res Labs, 6425 Penn Ave,Suite 400, Pittsburgh, PA 15206 USA. [Grindle, Garrett G.; Cooper, Rory A.] Univ Pittsburgh, Dept Rehabil Sci & Technol, 6425 Penn Ave,Suite 400, Pittsburgh, PA 15206 USA. RP Pasquina, PF (reprint author), Uniformed Serv Univ Hlth Sci, Ctr Rehabil Sci Res, Dept Phys Med & Rehabil, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.; Pasquina, PF (reprint author), Walter Reed Natl Mil Med Ctr, Dept Rehabil, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. FU Department of Defense [HU0001-11-1-0004, HU0001-15-2-0003]; Henry M. Jackson Foundation for the Advancement of Military Medicine FX This article is based on a work supported by the Department of Defense to the Center for Rehabilitation Science Research, Department of Physical Medicine and Rehabilitation, Uniformed Services University of Health Sciences (HU0001-11-1-0004, HU0001-15-2-0003) and The Henry M. Jackson Foundation for the Advancement of Military Medicine. NR 13 TC 0 Z9 0 U1 0 U2 0 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 EI 1930-613X J9 MIL MED JI Milit. Med. PD AUG PY 2016 VL 181 IS 8 BP E948 EP E951 DI 10.7205/MILMED-D-15-00315 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA DW5MI UT WOS:000383688900002 PM 27483540 ER PT J AU Moy, ML Martinez, CH Kadri, R Roman, P Holleman, RG Kim, HM Nguyen, HQ Cohen, MD Goodrich, DE Giardino, ND Richardson, CR AF Moy, Marilyn L. Martinez, Carlos H. Kadri, Reema Roman, Pia Holleman, Robert G. Kim, Hyungjin Myra Nguyen, Huong Q. Cohen, Miriam D. Goodrich, David E. Giardino, Nicholas D. Richardson, Caroline R. TI Long-Term Effects of an Internet-Mediated Pedometer-Based Walking Program for Chronic Obstructive Pulmonary Disease: Randomized Controlled Trial SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE bronchitis, chronic; emphysema; pulmonary disease, chronic obstructive; quality of life; exercise; motor activity; Internet ID DAILY STEP COUNT; QUALITY-OF-LIFE; PHYSICAL-ACTIVITY; PROSPECTIVE COHORT; CLINICAL-PRACTICE; HEALTH-STATUS; US COHORT; COPD; REHABILITATION; COMORBIDITIES AB Background: Regular physical activity (PA) is recommended for persons with chronic obstructive pulmonary disease (COPD). Interventions that promote PA and sustain long-term adherence to PA are needed. Objective: We examined the effects of an Internet-mediated, pedometer-based walking intervention, called Taking Healthy Steps, at 12 months. Methods: Veterans with COPD (N=239) were randomized in a 2:1 ratio to the intervention or wait-list control. During the first 4 months, participants in the intervention group were instructed to wear the pedometer every day, upload daily step counts at least once a week, and were provided access to a website with four key components: individualized goal setting, iterative feedback, educational and motivational content, and an online community forum. The subsequent 8-month maintenance phase was the same except that participants no longer received new educational content. Participants randomized to the wait-list control group were instructed to wear the pedometer, but they did not receive step-count goals or instructions to increase PA. The primary outcome was health-related quality of life (HRQL) assessed by the St George's Respiratory Questionnaire Total Score (SGRQ-TS); the secondary outcome was daily step count. Linear mixed-effect models assessed the effect of intervention over time. One participant was excluded from the analysis because he was an outlier. Within the intervention group, we assessed pedometer adherence and website engagement by examining percent of days with valid step-count data, number of log-ins to the website each month, use of the online community forum, and responses to a structured survey. Results: Participants were 93.7% male (223/238) with a mean age of 67 (SD 9) years. At 12 months, there were no significant between-group differences in SGRQ-TS or daily step count. Between-group difference in daily step count was maximal and statistically significant at month 4 (P<.001), but approached zero in months 8-12. Within the intervention group, mean 76.7% (SD 29.5) of 366 days had valid step-count data, which decreased over the months of study (P<.001). Mean number of log-ins at least once during the study by 83.8% (129/154) of participants. Responses to questions assessing participants' goal commitment and intervention engagement were not significantly different at 12 months compared to 4 months. Conclusions: An Internet-mediated, pedometer-based PA intervention, although efficacious at 4 months, does not maintain improvements in HRQL and daily step counts at 12 months. Waning pedometer adherence and website engagement by the intervention group were observed. Future efforts should focus on improving features of PA interventions to promote long-term behavior change and sustain engagement in PA. C1 [Moy, Marilyn L.] VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, Boston, MA USA. [Moy, Marilyn L.] Harvard Med Sch, Boston, MA USA. [Martinez, Carlos H.] Univ Michigan Hlth Syst, Pulm & Crit Care Div, Ann Arbor, MI USA. [Kadri, Reema; Richardson, Caroline R.] Univ Michigan, Dept Family Med, 1018 Fuller St, Ann Arbor, MI 48104 USA. [Kadri, Reema; Roman, Pia; Holleman, Robert G.; Kim, Hyungjin Myra; Goodrich, David E.; Richardson, Caroline R.] VA Ann Arbor Healthcare Syst, Ctr Clin Management Res, Ann Arbor, MI USA. [Kim, Hyungjin Myra] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Nguyen, Huong Q.] Kaiser Permanente Southern Calif, Dept Res & Evaluat, Pasadena, CA 91101 USA. [Cohen, Miriam D.] VA New York Harbor, Pulm Med Sect, Brooklyn, NY USA. [Giardino, Nicholas D.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. RP Richardson, CR (reprint author), Univ Michigan, Dept Family Med, 1018 Fuller St, Ann Arbor, MI 48104 USA. EM caroli@umich.edu OI Nguyen, Huong/0000-0002-3650-3705 FU Department of Veterans Affairs, Health Services Research and Development Service [IIR 09-366]; Department of Veterans Affairs, Rehabilitation Research and Development Service [F6847W]; NIH National Heart, Lung and Blood Institute [T32 HL007749-20] FX We thank the Veterans for their participation in this research study. The study was funded by Department of Veterans Affairs, Health Services Research and Development Service (Grant IIR 09-366, Richardson); Department of Veterans Affairs, Rehabilitation Research and Development Service (Career Development Award, F6847W, Moy); and NIH National Heart, Lung and Blood Institute (Grant T32 HL007749-20, Martinez). None of the funding bodies had any role in the design, collection, analysis or interpretation of the data, in writing the manuscript, or in the decision to submit the manuscript for publication. NR 45 TC 0 Z9 0 U1 2 U2 2 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PD AUG PY 2016 VL 18 IS 8 AR e215 DI 10.2196/jmir.5622 PG 14 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA EC9WT UT WOS:000388495700003 PM 27502583 ER PT J AU Pfammatter, A Spring, B Saligram, N Dave, R Gowda, A Blais, L Arora, M Ranjani, H Ganda, O Hedeker, D Reddy, S Ramalingam, S AF Pfammatter, Angela Spring, Bonnie Saligram, Nalini Dave, Raj Gowda, Arun Blais, Linelle Arora, Monika Ranjani, Harish Ganda, Om Hedeker, Donald Reddy, Sethu Ramalingam, Sandhya TI mHealth Intervention to Improve Diabetes Risk Behaviors in India: A Prospective, Parallel Group Cohort Study SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE mHealth; diabetes; health promotion ID PREVENTION PROGRAM; HEALTH; PROJECTIONS; PREVALENCE AB Background: In low/middle income countries like India, diabetes is prevalent and health care access limited. Most adults have a mobile phone, creating potential for mHealth interventions to improve public health. To examine the feasibility and initial evidence of effectiveness of mDiabetes, a text messaging program to improve diabetes risk behaviors, a global nonprofit organization (Arogya World) implemented mDiabetes among one million Indian adults. Objective: A prospective, parallel cohort design was applied to examine whether mDiabetes improved fruit, vegetable, and fat intakes and exercise. Methods: Intervention participants were randomly selected from the one million Nokia subscribers who elected to opt in to mDiabetes. Control group participants were randomly selected from non-Nokia mobile phone subscribers. mDiabetes participants received 56 text messages in their choice of 12 languages over 6 months; control participants received no contact. Messages were designed to motivate improvement in diabetes risk behaviors and increase awareness about the causes and complications of diabetes. Participant health behaviors (exercise and fruit, vegetable, and fat intake) were assessed between 2012 and 2013 via telephone surveys by blinded assessors at baseline and 6 months later. Data were cleaned and analyzed in 2014 and 2015. Results: 982 participants in the intervention group and 943 in the control group consented to take the phone survey at baselne. At the end of the 6-month period, 611 (62.22%) in the intervention and 632 (67.02%) in the control group completed the follow-up telephone survey. Participants receiving texts demonstrated greater improvement in a health behavior composite score over 6 months, compared with those who received no messages F(1, 1238) = 30.181, P<.001, 95% CI, 0.251-0.531. Fewer intervention participants demonstrated health behavior decline compared with controls. Improved fruit, vegetable, and fat consumption (P<.01) but not exercise were observed in those receiving messages, as compared with controls. Conclusions: A text messaging intervention was feasible and showed initial evidence of effectiveness in improving diabetes-related health behaviors, demonstrating the potential to facilitate population-level behavior change in a low/middle income country. C1 [Pfammatter, Angela; Spring, Bonnie] Northwestern Univ, Feinberg Sch Med, 680 N Lake Shore Dr,Suite 1400, Chicago, IL 60611 USA. [Saligram, Nalini; Ramalingam, Sandhya] Arogya World, Naperville, IL USA. [Dave, Raj] Hlth ARC, Pennington, NJ USA. [Gowda, Arun] Focus Sci Res Ctr, Bengaluru, India. [Blais, Linelle] Emory Univ, Emory Ctr Training & Tech Assistance, Atlanta, GA 30322 USA. [Blais, Linelle] Emory Univ, Emory Ctr Behav Sci & Hlth Educ, Atlanta, GA 30322 USA. [Arora, Monika] Publ Hlth Fdn India, New Delhi, Haryana, India. [Ranjani, Harish] Madras Diabet Res Fdn, Madras, Tamil Nadu, India. [Ganda, Om; Reddy, Sethu] Joslin Diabet Ctr, Boston, MA 02215 USA. [Hedeker, Donald] Univ Chicago, Chicago, IL 60637 USA. RP Pfammatter, A (reprint author), Northwestern Univ, Feinberg Sch Med, 680 N Lake Shore Dr,Suite 1400, Chicago, IL 60611 USA. EM angela.pfammatter@northwestern.edu RI Emchi, Karma/Q-1952-2016 FU Aetna International; Lifescan Inc. (a Johnson & Johnson company); MSD India; Amgen; Sanofi; Amarin Pharma FX The authors acknowledge study partners Nokia and Emory University and Mallory Stasko and H. Gene McFadden for their expertise, hard work, and support. This study was directed by Arogya World, which received funding from Aetna International, Lifescan Inc. (a Johnson & Johnson company), and MSD India. The funding sources had no involvement in the conduct of the study, writing of the manuscript, or decision to submit for publication. The research protocol was approved by the Centre for Chronic Disease Control of India, New Delhi and registered in the Australian New Zealand Clinical Trials Registry #ACTRN12615000423516. Linelle Blais received compensation to write the text messages used in the current study. Om Ganda has a grant with Amarin Pharma for an ongoing multi-center RCT, receives consulting fees from Amgen and Sanofi, and receives speaker honoraria from Merck and Janssen. S. Sethu Reddy was vice-president of medical affairs at Merck, Sharp, and Dohme until December of 2013 and receives speaker honoraria from Merck, Sharp, and Dohme. No financial disclosures were reported by other authors. NR 24 TC 2 Z9 2 U1 4 U2 4 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PD AUG PY 2016 VL 18 IS 8 AR e207 DI 10.2196/jmir.5712 PG 9 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA EC9WT UT WOS:000388495700012 PM 27496271 ER PT J AU Gullbrand, SE Ashinsky, BG Martin, JT Pickup, S Smith, LJ Mauck, RL Smith, HE AF Gullbrand, Sarah E. Ashinsky, Beth G. Martin, John T. Pickup, Stephen Smith, Lachlan J. Mauck, Robert L. Smith, Harvey E. TI Correlations Between Quantitative T2 and T1 rho MRI, Mechanical Properties and Biochemical Composition in a Rabbit Lumbar Intervertebral Disc Degeneration Model SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE T2; T1 rho; magnetic resonance imaging; intervertebral disc degeneration; biomechanics ID RELAXATION-TIMES; NUCLEUS PULPOSUS; PROTEOGLYCAN CONTENT; CARTILAGE; CHYMOPAPAIN; T-2 AB Improved diagnostic measures for intervertebral disc degeneration are necessary to facilitate early detection and treatment. The aim of this study was to correlate changes in mechanical and biochemical properties with the quantitative MRI parameters T2 and T1 rho in rabbit lumbar discs using an ex vivo chymopapain digestion model. Rabbit lumbar spinal motion segments from animals less than 6 months of age were injected with 100 mu l of saline (control) or chymopapain at 3, 15, or 100U/ml (n = 5 per group). T2 and T1 rho MRI series were obtained at 4.7T. Specimens were mechanically tested in tension-compression and creep. Normalized nucleus pulposus (NP) water and GAG contents were quantified. Stepwise multiple linear regression was performed to determine which parameters contributed significantly to changes in NP T2 and T1 rho. When all groups were included, multiple regression yielded a model with GAG, compressive modulus, and the creep time constants as variables significantly impacting T2 (multiple r(2) = 0.64, p = 0.006). GAG and neutral zone (NZ) modulus were identified as variables contributing to T1 rho (multiple r(2) = 0.28, p = 0.08). When specimens with advanced degeneration were excluded from the multiple regression analysis, T2 was significantly predicted by compressive modulus, tau(1), and water content (multiple r(2) = 0.71, p = 0.009), while no variables were significant predictors in the model for T1 rho. These results indicate that quantitative MRI can detect changes in the mechanical and biochemical properties of the degenerated disc. T2 may be more sensitive to early stage degenerative changes than T1 rho, while both quantitative MRI parameters are sensitive to advanced degeneration. (C) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. C1 [Gullbrand, Sarah E.; Ashinsky, Beth G.; Martin, John T.; Smith, Lachlan J.; Mauck, Robert L.; Smith, Harvey E.] Univ Penn, McKay Orthopaed Res Lab, Dept Orthopaed Surg, Philadelphia, PA 19104 USA. [Gullbrand, Sarah E.; Martin, John T.; Smith, Lachlan J.; Mauck, Robert L.; Smith, Harvey E.] Philadelphia VA Med Ctr, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA. [Pickup, Stephen] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Smith, Lachlan J.] Univ Penn, Dept Neurosurg, Philadelphia, PA 19104 USA. RP Smith, HE (reprint author), Univ Penn, McKay Orthopaed Res Lab, Dept Orthopaed Surg, Philadelphia, PA 19104 USA.; Smith, HE (reprint author), Philadelphia VA Med Ctr, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA. EM harvey.smith@uphs.upenn.edu FU Department of Veterans' Affairs [IK2 RX00147]; Penn Center for Musculoskeletal Disorders [P30 AR050950] FX Grant sponsor: Department of Veterans' Affairs; Grant number: IK2 RX00147; Grant sponsor: Penn Center for Musculoskeletal Disorders; Grant number: P30 AR050950. NR 33 TC 2 Z9 2 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-0266 EI 1554-527X J9 J ORTHOP RES JI J. Orthop. Res. PD AUG PY 2016 VL 34 IS 8 SI SI BP 1382 EP 1388 DI 10.1002/jor.23269 PG 7 WC Orthopedics SC Orthopedics GA DW5VU UT WOS:000383716300010 PM 27105019 ER PT J AU Muriuki, MG Havey, RM Voronov, LI Carandang, G Zindrick, MR Lorenz, MA Lomasney, L Patwardhan, AG AF Muriuki, Muturi G. Havey, Robert M. Voronov, Leonard I. Carandang, Gerard Zindrick, Michael R. Lorenz, Mark A. Lomasney, Laurie Patwardhan, Avinash G. TI Effects of Motion Segment Level, Pfirrmann Intervertebral Disc Degeneration Grade and Gender on Lumbar Spine Kinematics SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE range of motion; high and low flexibility zone; rotational stiffness; hysteresis; MRI ID ANULUS FIBROSUS; FLEXIBILITY; STIFFNESS; MECHANICS; BEHAVIOR AB MRI allows non-invasive assessment of intervertebral disc degeneration with the added clinical benefit of using nonionizing radiation. What has remained unclear is the relationship between assessed disc degeneration and lumbar spine kinematics. Kinematic outcomes of 54 multi-segment (L1-Sacrum) lumbar spine specimens were calculated to discover if such an underlying relationship exists with degeneration assessed using the Pfirrmann grading system. Further analyses were also conducted to determine if kinematic outcomes were affected by motion segment level, gender or applied compressive preload. Range of motion, hysteresis, high flexibility zone size and rotational stiffness in flexion-extension, lateral bending and axial rotation were the kinematic outcomes. Caudal intervertebral discs in our study sample were more degenerative than cranial discs. L5-S1 discs had the largest flexion-extension range of motion (p < 0.005) and L1-L2 discs the lowest flexion high flexibility zone size (p < 0.013). No other strict cranial-caudal differences in kinematic outcomes were found. Low flexibility zone rotational stiffness increased with disc degeneration grade in extension, lateral bending and axial rotation (p < 0.001). Trends towards higher hysteresis and lower range of motion with increased degeneration were observed in flexion-extension and lateral bending. Applied compressive preload increased flexion-extension hysteresis and augmented the effect of degeneration on hysteresis (p < 0.0005). Female specimens had about one degree larger range of motion in all rotational modes, and higher flexion extension hysteresis (p = 0.016). These results suggest that gender differences exist in lumbar spine kinematics. Additionally high disc loads, applied compressive preload or applied moment, are needed to kinematically distinguish discs with different levels of degeneration. (C) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. C1 [Muriuki, Muturi G.; Havey, Robert M.; Voronov, Leonard I.; Carandang, Gerard; Zindrick, Michael R.; Lorenz, Mark A.; Patwardhan, Avinash G.] US Dept Vet Affairs, Musculoskeletal Biomech Lab, Edward Hines Jr VA Hosp, Hines, IL 60141 USA. [Havey, Robert M.; Voronov, Leonard I.; Zindrick, Michael R.; Lorenz, Mark A.; Patwardhan, Avinash G.] Loyola Univ Chicago, Dept Orthopaed Surg & Rehabil, Maywood, IL USA. [Lomasney, Laurie] Loyola Univ Chicago, Dept Radiol, Maywood, IL USA. [Zindrick, Michael R.; Lorenz, Mark A.] Hinsdale Orthopaed Associates, Hinsdale, IL USA. RP Muriuki, MG (reprint author), US Dept Vet Affairs, Musculoskeletal Biomech Lab, Edward Hines Jr VA Hosp, Hines, IL 60141 USA. EM muturi_muriuki@yahoo.com OI Muriuki, Muturi/0000-0002-0620-9169 FU US Department of Veterans Affairs FX This work was supported in part by the US Department of Veterans Affairs. NR 26 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-0266 EI 1554-527X J9 J ORTHOP RES JI J. Orthop. Res. PD AUG PY 2016 VL 34 IS 8 SI SI BP 1389 EP 1398 DI 10.1002/jor.23232 PG 10 WC Orthopedics SC Orthopedics GA DW5VU UT WOS:000383716300011 PM 26990567 ER PT J AU Hanske, J Meyer, CP Sammon, JD Choueiri, TK Menon, M Lipsitz, SR Noldus, J Nguyen, PL Sun, M Trinh, QD AF Hanske, Julian Meyer, Christian P. Sammon, Jesse D. Choueiri, Toni K. Menon, Mani Lipsitz, Stuart R. Noldus, Joachim Nguyen, Paul L. Sun, Maxine Quoc-Dien Trinh TI The influence of marital status on the use of breast, cervical, and colorectal cancer screening SO PREVENTIVE MEDICINE LA English DT Article DE Preventive services; Screening; Cancer; USPSTF; Marital status; BRFSS ID PREVENTIVE SERVICES; PARTICIPATION; SURVIVAL; RISK AB Purpose. To examine the impact of marital status on the use of screening for breast, cervical, and colorectal cancer. Methods. Werelied on 2012 Behavioral Risk Factor Surveillance System Survey age-appropriate screening cohorts. Appropriate screening for breast, cervical, and colorectal cancerwas determined according to United States Preventive Services Task Force recommendations in effect at the time of the 2012 survey. Complex samples logistic regression models were performed to examine the effect of marital status on cancer screening. Results. Overall, 81.6, 83.9, and 68.9% of married participants underwent breast, cervical, and colorectal cancer, respectively, relative to 74.2, 75.1, and 60.9% for divorced/widowed/separated, individuals, and 74.7, 78.7, and 53.4% for never married individuals. Marital status (married vs. never married) was an independent predictor of screening for all cancers examined: breast cancer, odds ratio (OR): 1.42 (95% confidence interval [CI]: 1.251.61); cervical cancer, OR: 1.29 (95% CI: 1.16-1.43); colorectal cancer, OR: 1.63 (95% CI: 1.51-1.77). Gender-specific subgroup analyses for colorectal cancer suggests that marital status may exert a greater effect in men, relative to women (married men: OR 1.75, 95% CI: 1.56-1.96; married women: OR: 1.52, 95% CI: 1.35-1.70). Conclusion. Being married is associated with increased utilization of breast, cervical, and colorectal cancer screening. The influence of marital status was greater in men relative to women eligible for colorectal cancer screening. Our results emphasize the importance of social determinants of health-seeking behaviors. (C) 2016 Elsevier Inc. All rights reserved. C1 [Hanske, Julian; Meyer, Christian P.; Lipsitz, Stuart R.; Sun, Maxine; Quoc-Dien Trinh] Harvard Med Sch, Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA USA. [Hanske, Julian; Meyer, Christian P.; Lipsitz, Stuart R.; Sun, Maxine; Quoc-Dien Trinh] Harvard Med Sch, Brigham & Womens Hosp, Div Urol Surg, Boston, MA USA. [Hanske, Julian; Noldus, Joachim] Ruhr Univ Bochum, Marien Hosp, Dept Urol, Herne, Germany. [Meyer, Christian P.] Univ Med Ctr Hamburg Eppendorf, Dept Urol, Hamburg, Germany. [Sammon, Jesse D.; Menon, Mani] Henry Ford Hlth Syst, Vattikuti Urol Inst, Ctr Outcomes Res Analyt & Evaluat, Detroit, MI USA. [Choueiri, Toni K.] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Nguyen, Paul L.] Harvard Med Sch, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA USA. RP Trinh, QD (reprint author), Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Div Urol Surg, 45 Francis St,ASB 2-3, Boston, MA 02115 USA. EM qtrinh@bwh.harvard.edu FU Heinrich Hertz-Stiftung; Vattikuti Urology Institute; Walter Morris-Hale Distinguished Chair in Urologic Oncology at Brigham and Women's Hospital FX Julian Hanske is supported by a grant from the Heinrich Hertz-Stiftung. Quoc-Dien Trinh is supported by an unrestricted educational grant from the Vattikuti Urology Institute and the Professor Walter Morris-Hale Distinguished Chair in Urologic Oncology at Brigham and Women's Hospital. NR 25 TC 1 Z9 1 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 EI 1096-0260 J9 PREV MED JI Prev. Med. PD AUG PY 2016 VL 89 BP 140 EP 145 DI 10.1016/j.ypmed.2016.05.017 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA EC7KJ UT WOS:000388316700020 PM 27215758 ER PT J AU Muralidhar, V Nguyen, PL Tucker-Seeley, RD AF Muralidhar, Vinayak Nguyen, Paul L. Tucker-Seeley, Reginald D. TI Recent relocation and decreased survival following a cancer diagnosis SO PREVENTIVE MEDICINE LA English DT Article DE Relocation; Psychosocial stress; Cancer-specific mortality; Healthcare disparities; Metastatic cancer ID PSYCHOLOGICAL DISTRESS; OLDER-ADULTS; RESIDENTIAL-MOBILITY; SOCIOECONOMIC-STATUS; FINANCIAL HARDSHIP; SOCIAL NETWORKS; RISK-FACTORS; HEALTH; ASSOCIATION; MORTALITY AB Objective. To determine the impact of recent relocation prior to a cancer diagnosis on cancer-specific outcomes. Methods. We identified 272,718 patients with two different entries in the Surveillance, Epidemiology, and End Results database within 3 years of each other. Those who had relocated to a different county between entries were identified and we determined the risk of stage IV disease or cancer-specific mortality among relocators and non-relocators after adjusting for other patient-specific demographic and clinical factors. Results. A total of 4639( 1.7%) patients relocated to a new county within 3 years prior to a second cancer diagnosis and 268,079( 98.3%) patients did not. Patients who had relocated to a new area were more likely to be diagnosed with stage IV cancer( 25.2% vs. 20.8%; adjusted odds ratio = 1.27; 95% confidence interval [CI], 1.18-1.37; P < 0.001), and had an increased risk of 10-year cancer-specific mortality( 20.9% vs. 17.9%; adjusted hazard ratio 1.26; 95% CI, 1.17-1.36; P < 0.001). Conclusion. These results suggest that recent relocation to a new county prior to a cancer diagnosis is associated with an increased risk of late-stage presentation and worse cancer-specific mortality. (C) 2016 Elsevier Inc. All rights reserved. C1 [Muralidhar, Vinayak] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Nguyen, Paul L.] Harvard Med Sch, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Nguyen, Paul L.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA 02115 USA. [Tucker-Seeley, Reginald D.] Harvard TH Chan Sch Publ Hlth, Dana Farber Canc Inst, Ctr Community Based Res, Dept Social & Behav Sci, Boston, MA USA. RP Tucker-Seeley, RD (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, LW743,450 Brookline Ave, Boston, MA 02115 USA. EM vmuralidhar@partners.org; pnguyen@LROC.harvard.edu; retucker@hsph.harvard.edu FU IDEA2 Program - Peter C. Farrell Fund; Prostate Cancer Foundation; Fitz's Cancer Warriors; David and Cynthia Chapin; Hugh Simons in Honor of Frank and Anne Simons; Scott Forbes and Gina Ventre Fund; National Cancer Institute [CA169041] FX This work was supported by grants from the IDEA2 Program supported by the Peter C. Farrell (1967) Fund, The Prostate Cancer Foundation, Fitz's Cancer Warriors, David and Cynthia Chapin, Hugh Simons in Honor of Frank and Anne Simons, The Scott Forbes and Gina Ventre Fund, and an anonymous grant. Dr. Tucker-Seeley is funded by a K01 career development award (Grant # CA169041) from the National Cancer Institute. The funding sources had no role in the study. NR 44 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 EI 1096-0260 J9 PREV MED JI Prev. Med. PD AUG PY 2016 VL 89 BP 245 EP 250 DI 10.1016/j.ypmed.2016.06.007 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA EC7KJ UT WOS:000388316700034 PM 27287662 ER PT J AU Winkelman, JW Mackie, SE Mei, LA Platt, S Schoerning, L AF Winkelman, John W. Mackie, Susan E. Mei, Leslie A. Platt, Samuel Schoerning, Laura TI A method to switch from oral dopamine agonists to rotigotine in patients with restless legs syndrome and mild augmentation SO SLEEP MEDICINE LA English DT Article DE Restless legs syndrome; Rotigotine; Augmentation; Pramipexole; Ropinirole ID EKBOM DISEASE; DIAGNOSTIC-CRITERIA; TRANSDERMAL PATCH; PARKINSON-DISEASE; OVERNIGHT SWITCH; DOUBLE-BLIND; OPEN-LABEL; DAYTIME; EPIDEMIOLOGY; MANAGEMENT AB Background: We examined the short- and long-term efficacy and tolerability of a cross-titration algorithm from oral dopamine agonists to the rotigotine transdermal patch in patients dissatisfied with their restless legs syndrome (RLS) treatment, predominantly with mild augmentation. Methods: Patients with RLS (n = 20) were recruited at a single site. The cross-titration consisted of decreasing oral dopaminergic agents (ropinirole by 1 mg or pramipexole by 0.25 mg) and increasing rotigotine by 1 mg every two days. Efficacy and adverse events (AEs) were assessed at one, three, six and 12 months after the switch. Results: Patients had moderate severe RLS symptoms at the baseline (mean international restless legs syndrome (IRLS) score 19.4 +/- 5.5); 85% had augmentation and 45% reported afternoon RLS symptoms. The baseline mean pramipexole equivalent dose was 0.6 +/- 0.3 mg. At Week 5, 85% (17/20) had successfully switched from their oral dopamine agonist to rotigotine (mean dose 2.5 +/- 0.6 mg; change in IRLS score: 6.7 +/- 8.4, p = 0.002); 14 patients were CGI-I responders (much or very much improved). Three patients withdrew due to lack of efficacy. Twelve months after cross-titration, 10 patients continued on rotigotine, of whom four required either higher doses of rotigotine or supplemental RLS medication compared with their optimal Week 5 dose; five patients withdrew due to AEs and two due to lack of efficacy. Conclusion: A cross-titration to rotigotine was efficacious after five weeks in 70% of patients dissatisfied with RLS treatment, most of whom had mild augmentation. At one year following the medication switch, 50% had discontinued rotigotine due to lack of continued efficacy or side effects. (C) 2016 Elsevier B.V. All rights reserved. C1 [Winkelman, John W.; Mackie, Susan E.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq, Boston, MA 02114 USA. [Winkelman, John W.; Mackie, Susan E.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, 1 Bowdoin Sq, Boston, MA 02114 USA. Harvard Med Sch, Brigham & Womens Hosp, Dept Med, 25 Shattuck St, Boston, MA 02115 USA. [Mei, Leslie A.; Platt, Samuel] Massachusetts Gen Hosp, 1 Bowdoin Sq, Boston, MA 02114 USA. [Schoerning, Laura] Marian Univ, 3200 Cold Spring Rd, Indianapolis, IN USA. RP Winkelman, JW (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq, Boston, MA 02114 USA.; Winkelman, JW (reprint author), Massachusetts Gen Hosp, Dept Neurol, 1 Bowdoin Sq, Boston, MA 02114 USA. EM JWWINKELMAN@partners.org FU UCB Biosciences, Inc. FX This work was funded as an investigator-initiated trial by UCB Biosciences, Inc. Statistical and data management assistance was provided by Samuel Platt BA. NR 23 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1389-9457 EI 1878-5506 J9 SLEEP MED JI Sleep Med. PD AUG PY 2016 VL 23 BP 18 EP 23 DI 10.1016/j.sleep.2016.05.004 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA ED0ON UT WOS:000388541900003 PM 27810181 ER PT J AU Ellimoottil, C Skolarus, T Gettman, M Boxer, R Kutikov, A Lee, BR Shelton, J Morgan, T AF Ellimoottil, Chandy Skolarus, Ted Gettman, Matthew Boxer, Richard Kutikov, Alexander Lee, Benjamin R. Shelton, Jeremy Morgan, Todd TI Telemedicine in Urology: State of the Art SO UROLOGY LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; REMOTE VIDEO VISITS; RADICAL PROSTATECTOMY; FOLLOW-UP; CARE; SURGERY; TELEHEALTH; SATISFACTION; SYSTEM; REIMBURSEMENT AB Whereas telemedicine is recognized as one of the fastest-growing components of the healthcare system, the status of telemedicine use in urology is largely unknown. In this narrative review, we detail studies that investigate the use of televisits and teleconsultations for urologic conditions. Moreover, we discuss current regulatory and reimbursement policies. Finally, we discuss the significant barriers to widespread dissemination and implementation of telemedicine and reasons why the field of urology may be positioned to become a leader in the provision of telemedicine services. Published by Elsevier Inc. C1 Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. [Ellimoottil, Chandy] Univ Michigan, Inst Healthcare Policy & Innovat, 2800 Plymouth Rd,NCRC Bldg 14,G100-13, Ann Arbor, MI 48109 USA. VA Ann Arbor Healthcare Syst, Ctr Clin Management Res, Ann Arbor, MI USA. Mayo Clin, Coll Med, Dept Urol, Rochester, MN USA. Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA. Temple Univ Hlth Syst, Fox Chase Canc Ctr, Div Urol Oncol, Philadelphia, PA USA. Univ Arizona, Dept Urol, Tucson, AZ USA. Vet Affairs Greater Los Angeles, Los Angeles, CA USA. RP Ellimoottil, C (reprint author), Univ Michigan, Inst Healthcare Policy & Innovat, 2800 Plymouth Rd,NCRC Bldg 14,G100-13, Ann Arbor, MI 48109 USA. EM cellimoo@med.umich.edu FU Agency for Healthcare Research and Quality [1F32HS024193-01] FX This research was supported by the Agency for Healthcare Research and Quality (1F32HS024193-01 to Dr. Ellimoottil). NR 51 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 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD AUG PY 2016 VL 94 BP 10 EP 15 DI 10.1016/j.urology.2016.02.061 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA DW5OU UT WOS:000383696400010 PM 27109596 ER PT J AU Bennett, CL Prasad, SM Kennedy, WA AF Bennett, Charles L. Prasad, Sandip M. Kennedy, William A., II TI Telemedicine in Urology: State of the Art SO UROLOGY LA English DT Editorial Material C1 [Bennett, Charles L.] Univ South Carolina, Coll Pharm, Hollins Natl Canc Inst, Designated Canc Ctr, Charleston, SC 29424 USA. [Prasad, Sandip M.] Med Univ South Carolina, Dept Urol, Charleston, SC USA. [Prasad, Sandip M.] Ralph H Johnson VAMC, Dept Surg, Urol Sect, Charleston, SC USA. [Kennedy, William A., II] Stanford Univ, Med Ctr, Dept Urol, Palo Alto, CA 94304 USA. RP Bennett, CL (reprint author), Univ South Carolina, Coll Pharm, Hollins Natl Canc Inst, Designated Canc Ctr, Charleston, SC 29424 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD AUG PY 2016 VL 94 BP 15 EP 16 DI 10.1016/j.urology.2016.02.062 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA DW5OU UT WOS:000383696400011 PM 27207146 ER PT J AU Midkiff, KD Andrews, EB Gilsenan, AW Deapen, DM Harris, DH Schymura, MJ Hornicek, FJ AF Midkiff, Kirk D. Andrews, Elizabeth B. Gilsenan, Alicia W. Deapen, Dennis M. Harris, David H. Schymura, Maria J. Hornicek, Francis J. TI The experience of accommodating privacy restrictions during implementation of a large-scale surveillance study of an osteoporosis medication SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE epidemiology; oncology; postmarketing product surveillance; privacy; public health; survey; retrospective studies; pharmacoepidemiology ID HEALTH RESEARCH; IMPACT; RULE; BIAS AB Purpose To explore whether privacy restrictions developed to protect patients have complicated research within a 15-year surveillance study conducted with US cancer registries. Methods Data from enrolling 27 cancer registries over a 10-year period were examined to describe the amount of time needed to obtain study approval. We also analyzed the proportion of patients that completed a research interview out of the total reported by the registries and examined factors thought to influence this measure. Results The average length of the research review process from submission to approval of the research was 7 months (range, <1 to 24 months), and it took 6 months or more to obtain approval of the research at 41% of the cancer registries. Most registries (78%) required additional permission steps to gain access to patients for research. After adjustment for covariates, the interview response proportion was 110% greater (ratio of response proportion = 2.1; 95% confidence interval: 1.3, 3.3) when the least restrictive versus the most restrictive permission steps were required. An interview was more often completed for patients (or proxies) if patients were alive, within a year of being diagnosed, or identified earlier in the study. Conclusions Lengthy research review processes increased the time between diagnosis and provision of patient information to the researcher. Requiring physician permission for access to patients was associated with lower subject participation. A single national point of entry for use of cancer registry data in health research is worthy of consideration to make the research approval process efficient. (C) 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd. C1 [Midkiff, Kirk D.; Andrews, Elizabeth B.; Gilsenan, Alicia W.; Harris, David H.] RTI Int, RTI Hlth Solut, Dept Pharmacoepidemiol & Risk Management, 3040 Cornwallis Rd,POB 12194, Res Triangle Pk, NC 27709 USA. [Deapen, Dennis M.] Univ Southern Calif, Keck Sch Med, Los Angeles Canc Surveillance Program, Los Angeles, CA USA. [Schymura, Maria J.] New York State Dept Hlth, New York State Canc Registry, Albany, NY USA. [Hornicek, Francis J.] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. RP Midkiff, KD (reprint author), RTI Int, RTI Hlth Solut, Dept Pharmacoepidemiol & Risk Management, 3040 Cornwallis Rd,POB 12194, Res Triangle Pk, NC 27709 USA. EM kmidkiff@rti.org FU Eli Lilly Company FX The surveillance study, which served as the basis for the analysis in this paper, is being conducted by RTI International with support from Eli Lilly & Company. Drs. Deapen, Schymura, and Hornicek did not receive funding to support this work. The analyses presented in this paper were initiated by the investigators and not the sponsoring agency. The authors would like to thank Dr. Kenneth Rothman for his guidance on analytical methods and careful and considerate review of the paper. The authors would like to thank Mr. Dave McSorley for his careful review of the programming code and for his assistance in preparation of additional adjusted estimates. The authors also thank Ms. Ginger Powell, Ms. Diana Goss, and Ms. Amy Ladner for their ongoing contributions to this study, especially with regard to data management. Finally, this analysis would not have been possible without the participation and support of the cancer registries that have agreed to identify cases for the ongoing postmarketing study. Data used in this report were provided by the following individual cancer registries and departments of health: Alabama Department of Public Health; Alabama Statewide Cancer Registry; Arizona Department of Health Services; Arizona Cancer Registry; California Department of Public Health; California Cancer Registry; Colorado Department of Public Health and Environment; Colorado Central Cancer Registry; Florida Department of Health; Florida Cancer Data System; Dana Farber/Harvard Cancer Center; Brigham and Women's Hospital; Massachusetts General Hospital; University of Hawaii Cancer Center, Hawaii Tumor Registry; the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Indiana State Department of Health; Indiana State Cancer Registry; University of Iowa; State Health Registry of Iowa; University of Kentucky, Markey Cancer Control Program; Kentucky Cancer Registry, University of Southern California Cancer Surveillance Program; Louisiana State University Health Sciences Center; Louisiana Tumor Registry; Michigan Department of Community Health; Michigan Cancer Surveillance Program; Minnesota Department of Health; Minnesota Cancer Surveillance System; University of Missouri; Missouri Cancer Registry; North Carolina Department of Health and Human Services, Division of Public Health; North Carolina Central Cancer Registry; The Rutgers Cancer Institute of New Jersey, Rutgers University; New Jersey State Cancer Registry; New York State Department of Health; New York State Cancer Registry; Ohio Department of Health; Ohio Cancer Incidence Surveillance System; Bureau of Health Statistics & Research, Pennsylvania Department of Health; Pennsylvania Cancer Registry; South Carolina Department of Health and Environmental Control; South Carolina Central Cancer Registry; Tennessee Department of Health; Tennessee Cancer Registry; Texas Department of State Health Services; Texas Cancer Registry; University of Texas M.D. Anderson Cancer Center; University of Utah; Utah Cancer Registry; State of Washington Department of Social and Health Services; Washington State Cancer Registry; the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI); and the National Program of Cancer Registries (NPCR) of the Centers for Disease Control and Prevention (CDC). Use of these data does not imply that these registries, their departments of health, the CDC, or NCI either agrees or disagrees with any representations, analyses, interpretations, or conclusions. NR 19 TC 2 Z9 2 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 AUG PY 2016 VL 25 IS 8 BP 960 EP 968 DI 10.1002/pds.4008 PG 9 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA DW4VW UT WOS:000383642100012 PM 27091234 ER PT J AU Cuaron, JJ MacDonald, SM Cahlon, O AF Cuaron, John J. MacDonald, Shannon M. Cahlon, Oren TI Novel applications of proton therapy in breast carcinoma SO CHINESE CLINICAL ONCOLOGY LA English DT Review DE Protons; breast cancer; indications; technique ID RELATIVE BIOLOGICAL EFFECTIVENESS; MODULATED RADIATION-THERAPY; EXTERNAL-BEAM RADIOTHERAPY; PROSPECTIVE CLINICAL-TRIAL; EFFECTIVENESS RBE VALUES; LINEAR-ENERGY-TRANSFER; PHASE-II TRIAL; EARLY-STAGE; RANDOMIZED-TRIAL; CANCER PATIENTS AB This review will focus on the indications, clinical experience, and technical considerations of proton beam radiation therapy in the treatment of patients with breast cancer. For patients with early stage disease, proton therapy delivers less dose to non-target breast tissue for patients receiving partial breast irradiation ( PBI) therapy, which may result in improved cosmesis but requires further investigation. For patients with locally advanced breast cancer requiring treatment to the regional lymph nodes, proton therapy allows for an improved dosimetric profile compared with conventional photon and electron techniques. Early clinical results demonstrate acceptable toxicity. The possible reduction in cardiopulmonary events as a result of reduced dose to organs at risk will be tested in a randomized control trial of protons vs. photons. C1 [Cuaron, John J.; Cahlon, Oren] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA. [MacDonald, Shannon M.] Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. RP Cuaron, JJ (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA. EM cuaronj@mskcc.org NR 88 TC 0 Z9 0 U1 2 U2 2 PU AME PUBL CO PI SHEUNG WAN PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG 00000, PEOPLES R CHINA SN 2304-3865 EI 2304-3873 J9 CHIN CLIN ONCOL JI Chin. Clin. Oncol. PD AUG PY 2016 VL 5 IS 4 AR UNSP 52 DI 10.21037/cco.2016.06.04 PG 15 WC Oncology SC Oncology GA EB7QR UT WOS:000387585100006 PM 27558253 ER PT J AU Kass, JI Mehta, V AF Kass, Jason I. Mehta, Vikas TI Positron emission tomography-CT surveillance versus neck dissection in advanced head and neck cancer: time for a paradigm shift in management SO TRANSLATIONAL CANCER RESEARCH LA English DT Editorial Material ID SQUAMOUS-CELL CARCINOMA; PET/CT C1 [Kass, Jason I.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Div Otolaryngol Head & Neck Surg, Boston, MA 02218 USA. [Mehta, Vikas] LSU Hlth Sci Ctr Shreveport, Dept Otolaryngol Head & Neck Surg, 1501 Kings Hwy Room 9-203, Shreveport, LA 71130 USA. RP Mehta, V (reprint author), LSU Hlth Sci Ctr Shreveport, Dept Otolaryngol Head & Neck Surg, 1501 Kings Hwy Room 9-203, Shreveport, LA 71130 USA. EM dr.vikasmehta@gmail.com NR 8 TC 0 Z9 0 U1 0 U2 0 PU AME PUBL CO PI SHEUNG WAN PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG 00000, PEOPLES R CHINA SN 2218-676X EI 2219-6803 J9 TRANSL CANCER RES JI Transl. Cancer Res. PD AUG PY 2016 VL 5 SU 2 BP S203 EP S204 DI 10.21037/tcr.2016.08.03 PG 2 WC Oncology SC Oncology GA EB4KI UT WOS:000387340000013 ER PT J AU Li, GZ Raut, CP AF Li, George Z. Raut, Chandrajit P. TI Pazopanib: a new therapeutic option for advanced gastrointestinal stromal tumors SO TRANSLATIONAL CANCER RESEARCH LA English DT Editorial Material C1 [Li, George Z.; Raut, Chandrajit P.] Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. [Raut, Chandrajit P.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. RP Raut, CP (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM craut@bwh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AME PUBL CO PI SHEUNG WAN PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG 00000, PEOPLES R CHINA SN 2218-676X EI 2219-6803 J9 TRANSL CANCER RES JI Transl. Cancer Res. PD AUG PY 2016 VL 5 SU 2 BP S240 EP S242 DI 10.21037/tcr.2016.08.14 PG 3 WC Oncology SC Oncology GA EB4KI UT WOS:000387340000022 ER PT J AU Goel, S Krop, IE AF Goel, S. Krop, I. E. TI PIK3CA mutations in HER2-positive breast cancer: an ongoing conundrum SO ANNALS OF ONCOLOGY LA English DT Editorial Material C1 [Goel, S.; Krop, I. E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Krop, IE (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM ian_krop@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD AUG PY 2016 VL 27 IS 8 BP 1368 EP 1372 DI 10.1093/annonc/mdw246 PG 5 WC Oncology SC Oncology GA DV8JH UT WOS:000383182800003 PM 27358378 ER PT J AU Scelo, G Hofmann, JN Banks, RE Bigot, P Bhatt, RS Cancel-Tassin, G Chew, SK Creighton, CJ Cussenot, O Davis, IJ Escudier, B Frayling, TM Haggstrom, C Hildebrandt, MAT Holcatova, I Johansson, M Linehan, WM McDermott, DF Nathanson, KL Ogawa, S Perlman, EJ Purdue, MP Stattin, P Swanton, C Vasudev, NS Wu, X Znaor, A Brennan, P Chanock, SJ AF Scelo, G. Hofmann, J. N. Banks, R. E. Bigot, P. Bhatt, R. S. Cancel-Tassin, G. Chew, S. K. Creighton, C. J. Cussenot, O. Davis, I. J. Escudier, B. Frayling, T. M. Haggstrom, C. Hildebrandt, M. A. T. Holcatova, I. Johansson, M. Linehan, W. M. McDermott, D. F. Nathanson, K. L. Ogawa, S. Perlman, E. J. Purdue, M. P. Stattin, P. Swanton, C. Vasudev, N. S. Wu, X. Znaor, A. Brennan, P. Chanock, S. J. TI International cancer seminars: a focus on kidney cancer SO ANNALS OF ONCOLOGY LA English DT Article DE kidney cancer; genomics; epidemiology; clinical research ID RENAL-CELL CARCINOMA; GENOME-WIDE ASSOCIATION; GENETIC-BASIS; HETEROGENEITY; LANDSCAPE; DISEASE; TUMOR; RISK AB Recent years have seen important advances in our understanding of the etiology, biology and genetics of kidney cancer. To summarize important achievements and identify prominent research questions that remain, a workshop was organized by IARC and the US NCI. A series of 'difficult questions' were formulated, which should be given future priority in the areas of population, genomic and clinical research.Recent years have seen important advances in our understanding of the etiology, biology and genetics of kidney cancer. To summarize important achievements and identify prominent research questions that remain, a workshop was organized by IARC and the US NCI. A series of 'difficult questions' were formulated, which should be given future priority in the areas of population, genomic and clinical research. C1 [Scelo, G.; Johansson, M.; Znaor, A.; Brennan, P.] Int Agcy Res Canc, Sect Genet, 150 Cours Albert Thomas, F-69372 Lyon 08, France. [Hofmann, J. N.; Purdue, M. P.; Chanock, S. J.] NCI, Div Canc Epidemiol & Genet, US Dept HHS, NIH, Bethesda, MD 20892 USA. [Banks, R. E.; Vasudev, N. S.] St James Univ Hosp, Leeds Inst Canc Studies & Pathol, Canc Res UK Ctr, Clin & Biomed Prote Grp, Leeds, W Yorkshire, England. [Bigot, P.] CHU Angers, Dept Urol, Angers, France. [Bhatt, R. S.; McDermott, D. F.] Dana Farber Harvard Canc Ctr, Kidney Canc Program, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA USA. [Cancel-Tassin, G.; Cussenot, O.] CeRePP, Grp Rech GRC UPMC 5, Paris, France. [Chew, S. K.] UCL, UCL Canc Inst, Translat Canc Therapeut Lab, London, England. [Creighton, C. J.] Baylor Coll Med, Duncan Canc Center Biostat, Houston, TX 77030 USA. [Davis, I. J.] UNC, Sch Med, Dept Genet, Chapel Hill, NC USA. [Escudier, B.] Inst Gustave Roussy, Dept Med Oncol, Villejuif, France. [Frayling, T. M.] Univ Exeter, Sch Med, Exeter, Devon, England. [Haggstrom, C.; Stattin, P.] Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden. [Haggstrom, C.] Umea Univ, Dept Biobank Res, Umea, Sweden. [Hildebrandt, M. A. T.] Univ Texas MD Anderson Canc Ctr, Canc Prevent & Populat Sci, Div OVP, Dept Epidemiol, Houston, TX 77030 USA. [Holcatova, I.] Charles Univ Prague, Fac Med 2, Inst Publ Hlth & Prevent Med, Prague, Czech Republic. [Linehan, W. M.] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Nathanson, K. L.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Ogawa, S.] Univ Tokyo, Grad Sch Med, Tokyo, Japan. [Perlman, E. J.] Northwestern Univ, Dept Pathol, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Swanton, C.] UCL, Hosp & Canc Inst, London, England. [Wu, X.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. RP Brennan, P (reprint author), Int Agcy Res Canc, Sect Genet, 150 Cours Albert Thomas, F-69372 Lyon 08, France. EM brennanp@iarc.fr OI Cancel-Tassin, Geraldine/0000-0002-9583-6382 FU International Agency for Research on Cancer (IARC); Division of Cancer Epidemiology and Genetics (DCEG) of the US National Cancer Institute FX Organization of production of this seminar was funded jointly by the International Agency for Research on Cancer (IARC) and the Division of Cancer Epidemiology and Genetics (DCEG) of the US National Cancer Institute (no grant number applicable). NR 31 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD AUG PY 2016 VL 27 IS 8 BP 1382 EP 1385 DI 10.1093/annonc/mdw186 PG 4 WC Oncology SC Oncology GA DV8JH UT WOS:000383182800008 PM 27130845 ER PT J AU Clement, PM Gauler, T Machiels, JP Haddad, RI Fayette, J Licitra, LF Tahara, M Cohen, EEW Cupissol, D Grau, JJ Guigay, J Caponigro, F de Castro, G de Souza Viana, L Keilholz, U del Campo, JM Cong, XJ Ehrnrooth, E Vermorken, JB AF Clement, P. M. Gauler, T. Machiels, J. P. Haddad, R. I. Fayette, J. Licitra, L. F. Tahara, M. Cohen, E. E. W. Cupissol, D. Grau, J. J. Guigay, J. Caponigro, F. de Castro, G., Jr. de Souza Viana, L. Keilholz, U. del Campo, J. M. Cong, X. J. Ehrnrooth, E. Vermorken, J. B. CA LUX-H&N 1 Investigators TI Afatinib versus methotrexate in older patients with second-line recurrent and/or metastatic head and neck squamous cell carcinoma: subgroup analysis of the LUX-Head & Neck 1 trial(aEuro) SO ANNALS OF ONCOLOGY LA English DT Article DE afatinib; methotrexate; HNSCC; second-line; phase III; older ID CHEMOTHERAPY PLUS CETUXIMAB; PLATINUM-BASED THERAPY; OPEN-LABEL; CANCER AB In the LUX-Head & Neck 1 study, older age (a parts per thousand yen65 years) did not adversely affect the benefit in patient-reported outcomes and antitumor activity observed with afatinib over methotrexate, which was consistent with findings from the overall population. Safety in older patients was also consistent with the overall population, favoring afatinib in terms of fewer dose reductions and discontinuations.In the phase III LUX-Head & Neck 1 (LHN1) trial, afatinib significantly improved progression-free survival (PFS) versus methotrexate in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients progressing on/after platinum-based therapy. This report evaluates afatinib efficacy and safety in prespecified subgroups of patients aged a parts per thousand yen65 and < 65 years. Patients were randomized (2:1) to 40 mg/day oral afatinib or 40 mg/m(2)/week intravenous methotrexate. PFS was the primary end point; overall survival (OS) was the key secondary end point. Other end points included: objective response rate (ORR), patient-reported outcomes, tumor shrinkage, and safety. Disease control rate (DCR) was also assessed. Of 483 randomized patients, 27% (83 afatinib; 45 methotrexate) were aged a parts per thousand yen65 years (older) and 73% (239 afatinib; 116 methotrexate) < 65 years (younger) at study entry. Similar PFS benefit with afatinib versus methotrexate was observed in older {median 2.8 versus 2.3 months, hazard ratio (HR) = 0.68 [95% confidence interval (CI) 0.45-1.03], P = 0.061} and younger patients [2.6 versus 1.6 months, HR = 0.79 (0.62-1.01), P = 0.052]. In older and younger patients, the median OS with afatinib versus methotrexate was 7.3 versus 6.4 months [HR = 0.84 (0.54-1.31)] and 6.7 versus 6.2 months [HR = 0.98 (0.76-1.28)]. ORRs with afatinib versus methotrexate were 10.8% versus 6.7% and 10.0% versus 5.2%; DCRs were 53.0% versus 37.8% and 47.7% versus 38.8% in older and younger patients, respectively. In both subgroups, the most frequent treatment-related adverse events were rash/acne (73%-77%) and diarrhea (70%-80%) with afatinib, and stomatitis (43%) and fatigue (31%-34%) with methotrexate. Fewer treatment-related discontinuations were observed with afatinib (each subgroup 7% versus 16%). A trend toward improved time to deterioration of global health status, pain, and swallowing with afatinib was observed in both subgroups. Advancing age (a parts per thousand yen65 years) did not adversely affect clinical outcomes or safety with afatinib versus methotrexate in second-line R/M HNSCC patients. NCT01345682 (ClinicalTrials.gov). C1 [Clement, P. M.] Katholieke Univ Leuven, Dept Oncol, Herestr 49, B-3000 Leuven, Belgium. [Clement, P. M.] UZ Leuven, Dept Gen Med Oncol, Leuven, Belgium. [Gauler, T.] Univ Hosp Essen, West German Canc Ctr, Dept Med Canc Res, Essen, Germany. [Machiels, J. P.] Catholic Univ Louvain, Clin Univ St Luc, Med Oncol Serv, Inst Roi Albert 2, Brussels, Belgium. [Machiels, J. P.] Catholic Univ Louvain, Inst Rech Clin & Expt Pole MIRO, Brussels, Belgium. [Haddad, R. I.] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Fayette, J.] Univ Lyon, Ctr Leon Berard, Dept Med Oncol, Lyon, France. [Licitra, L. F.] Fdn IRCCS Ist Nazl Tumori, Dept Med Oncol, Milan, Italy. [Tahara, M.] Natl Canc Ctr Hosp East, Head & Neck Med Oncol, Kashiwa, Chiba, Japan. [Cohen, E. E. W.] Univ Calif San Diego, Dept Med, Moores Canc Ctr, La Jolla, CA 92093 USA. [Cupissol, D.] Inst Canc Montpellier Val dAurelle, Med Oncol Serv, Montpellier, France. [Grau, J. J.] Hosp Clin Barcelona, Dept Med Oncol, Barcelona, Spain. [Grau, J. J.] Univ Barcelona, Barcelona, Spain. [Guigay, J.] Gustave Roussy, Dept Med Oncol, Villejuif, France. [Guigay, J.] Ctr Antoine Lacassagne, Nice, France. [Caponigro, F.] Natl Tumor Inst Naples, Head & Neck Med Oncol, Head & Neck, Dept Melanoma,Soft Tissues,Muscolo Scheletal, Naples, Italy. [de Castro, G., Jr.] Inst Canc Estado Sao Paulo, Oncol Clin, Sao Paulo, Brazil. [de Souza Viana, L.] Hosp Canc Barretos, Dept Med Oncol, Sao Paulo, Brazil. [Keilholz, U.] Charite Comprehens Canc Ctr, Berlin, Germany. [del Campo, J. M.] Hosp Univ Vall DHebron, Dept Med Oncol, Barcelona, Spain. [Cong, X. J.] Boehringer Ingelheim Pharmaceut Inc, Biometr & Data Management, Ridgefield, CT USA. [Ehrnrooth, E.] Boehringer Ingelheim Danmark AS, Div Oncol, Copenhagen, Denmark. [Vermorken, J. B.] Univ Antwerp Hosp, Dept Med Oncol, Edegem, Belgium. RP Clement, PM (reprint author), Katholieke Univ Leuven, Dept Oncol, Herestr 49, B-3000 Leuven, Belgium. EM paul.clement@uzleuven.be RI Licitra, Lisa/C-6271-2017 OI Licitra, Lisa/0000-0003-0623-4118 FU Boehringer Ingelheim FX This work was supported by Boehringer Ingelheim. There is no applicable grant number for this work. NR 15 TC 2 Z9 2 U1 3 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD AUG PY 2016 VL 27 IS 8 BP 1585 EP 1593 DI 10.1093/annonc/mdw151 PG 9 WC Oncology SC Oncology GA DV8JH UT WOS:000383182800029 PM 27084954 ER PT J AU Nipp, RD El-Jawahri, A Fishbein, JN Gallagher, ER Stagl, JM Park, ER Jackson, VA Pirl, WF Greer, JA Temel, JS AF Nipp, R. D. El-Jawahri, A. Fishbein, J. N. Gallagher, E. R. Stagl, J. M. Park, E. R. Jackson, V. A. Pirl, W. F. Greer, J. A. Temel, J. S. TI Factors associated with depression and anxiety symptoms in family caregivers of patients with incurable cancer(aEuro) SO ANNALS OF ONCOLOGY LA English DT Article DE palliative care; mood; advanced cancer; caregivers; depression; anxiety ID QUALITY-OF-LIFE; ILL CANCER-PATIENTS; BURDEN; PREPAREDNESS; PREVALENCE; PROGNOSIS; DISTRESS; HEALTH; NEEDS AB In this study, we found that patients with incurable cancer and their family caregivers experience high rates of depression and anxiety symptoms, with FC anxiety levels exceeding those of the patients. We identified patient and FC factors associated with FCs' psychological distress, including patients' coping strategies and prognostic understanding.Family caregivers (FCs) are critically important for patients with cancer, yet they may experience psychological distress related to caregiving demands. We sought to describe rates of depression and anxiety in FCs of patients with incurable cancer and identify factors associated with these symptoms to determine those at greatest risk for psychological distress. We performed a cross-sectional analysis of baseline data from a randomized trial of early palliative care. We assessed depression and anxiety using the Hospital Anxiety and Depression Scale in patients within 8 weeks of diagnosis of incurable lung or gastrointestinal cancer and their FCs. We also assessed patients' quality of life (Functional Assessment of Cancer Therapy-General), coping strategies (Brief COPE), and their report of the primary goal of their cancer treatment. We used linear regression with purposeful selection of covariates to identify factors associated with FC depression and anxiety symptoms. We enrolled 78.6% (n = 275) of potentially eligible FCs. The majority were female (69.1%) and married to the patient (66.2%). While the proportion of FCs and patients reporting depression did not differ (16.4% versus 21.5%, P = 0.13), FCs were more likely to report anxiety compared with patients (42.2% versus 28.4%, P < 0.001). Patients' use of acceptance coping was associated with lower FC depression (B = -0.42, P < 0.001), while emotional support coping was associated with higher FC depression (B = 0.69, P = 0.001) and lower FC anxiety (B = -0.70, P < 0.001). Patient report that their primary goal of their treatment was to 'cure my cancer' was associated with higher FC depression (B = 0.72, P = 0.03). Patients with incurable cancer and their FCs report high levels of depression and anxiety symptoms. We demonstrated that patients' coping strategies and prognostic understanding were associated with FC depression and anxiety symptoms, underscoring the importance of targeting these risk factors when seeking to address the psychological distress experienced by FCs. C1 [Nipp, R. D.; El-Jawahri, A.; Gallagher, E. R.; Temel, J. S.] Massachusetts Gen Hosp, Dept Med, Div Hematol & Oncol, Boston, MA 02114 USA. [Fishbein, J. N.; Stagl, J. M.; Park, E. R.; Pirl, W. F.; Greer, J. A.] Massachusetts Gen Hosp, Dept Psychiat, Div Palliat Care, Boston, MA 02114 USA. [Jackson, V. A.] Massachusetts Gen Hosp, Dept Med, Div Palliat Care, Boston, MA 02114 USA. [Nipp, R. D.] Harvard Med Sch, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA. RP Nipp, RD (reprint author), Harvard Med Sch, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA.; Nipp, RD (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol & Oncol, Dept Med, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA. EM rnipp@mgh.harvard.edu FU National Institute of Nursing Research [NR012735]; National Cancer Institute [CA181253] FX This work was supported by the National Institute of Nursing Research R01 (NR012735 to JST); and the National Cancer Institute K24 (CA181253 to JST). NR 26 TC 1 Z9 1 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD AUG PY 2016 VL 27 IS 8 BP 1607 EP 1612 DI 10.1093/annonc/mdw205 PG 6 WC Oncology SC Oncology GA DV8JH UT WOS:000383182800032 PM 27177859 ER PT J AU Hashim, D Sartori, S Brennan, P Curado, MP Wunsch, V Divaris, K Olshan, AF Zevallos, JP Winn, DM Franceschi, S Castellsague, X Lissowska, J Rudnai, P Matsuo, K Morgenstern, H Chen, C Vaughan, TL Hofmann, JN D'Souza, G Haddad, RI Wu, H Lee, YC Hashibe, M La Vecchia, C Boffetta, P AF Hashim, D. Sartori, S. Brennan, P. Curado, M. P. Wunsch-Filho, V. Divaris, K. Olshan, A. F. Zevallos, J. P. Winn, D. M. Franceschi, S. Castellsague, X. Lissowska, J. Rudnai, P. Matsuo, K. Morgenstern, H. Chen, C. Vaughan, T. L. Hofmann, J. N. D'Souza, G. Haddad, R. I. Wu, H. Lee, Y. -C. Hashibe, M. La Vecchia, C. Boffetta, P. TI The role of oral hygiene in head and neck cancer: results from International Head and Neck Cancer Epidemiology (INHANCE) consortium SO ANNALS OF ONCOLOGY LA English DT Article DE head and neck neoplasms; oral neoplasms; pharyngeal neoplasms; oral hygiene; pooled analyses ID SQUAMOUS-CELL CARCINOMA; ILL-FITTING DENTURES; RISK-FACTORS; PERIODONTAL-DISEASE; DIABETES-MELLITUS; POOLED ANALYSIS; TOOTH LOSS; HEALTH; COHORT; ALCOHOL AB This pooled analysis describes the largest and most comprehensive assessment of the association between oral hygiene indicators and HNCs to date, including oral cavity, laryngeal, hypopharyngeal, and oropharyngeal cancers. We found good oral hygiene is associated with lower risk of HNC. Improvements in oral hygiene by increasing oral hygiene literacy, particularly for annual dentist visits and daily tooth brushing, may be protective against HNC.Poor oral hygiene has been proposed to contribute to head and neck cancer (HNC) risk, although causality and independency of some indicators are uncertain. This study investigates the relationship of five oral hygiene indicators with incident HNCs. In a pooled analysis of 8925 HNC cases and 12 527 controls from 13 studies participating in the International Head and Neck Cancer Epidemiology Consortium, comparable data on good oral hygiene indicators were harmonized. These included: no denture wear, no gum disease (or bleeding), < 5 missing teeth, tooth brushing at least daily, and visiting a dentist a parts per thousand yenonce a year. Logistic regression was used to estimate the effects of each oral hygiene indicator and cumulative score on HNC risk, adjusting for tobacco smoking and alcohol consumption. Inverse associations with any HNC, in the hypothesized direction, were observed for < 5 missing teeth [odds ratio (OR) = 0.78; 95% confidence interval (CI) 0.74, 0.82], annual dentist visit (OR = 0.82; 95% CI 0.78, 0.87), daily tooth brushing (OR = 0.83, 95% CI 0.79, 0.88), and no gum disease (OR = 0.94; 95% CI 0.89, 0.99), and no association was observed for wearing dentures. These associations were relatively consistent across specific cancer sites, especially for tooth brushing and dentist visits. The population attributable fraction for a parts per thousand currency sign 2 out of 5 good oral hygiene indicators was 8.9% (95% CI 3.3%, 14%) for oral cavity cancer. Good oral hygiene, as characterized by few missing teeth, annual dentist visits, and daily tooth brushing, may modestly reduce the risk of HNC. C1 [Sartori, S.; Wu, H.; Boffetta, P.] Icahn Sch Med Mt Sinai, Inst Translat Epidemiol, New York, NY 10029 USA. [Brennan, P.; Franceschi, S.] Int Agcy Res Canc, Lyon, France. [Curado, M. P.] CIPE ACCAMARGO, Epidemiol, Sao Paulo, Brazil. [Wunsch-Filho, V.] Univ Sao Paulo, Sch Publ Hlth, Sao Paulo, Brazil. [Divaris, K.] Univ N Carolina, Sch Publ Hlth, Dept Pediat Dent, Chapel Hill, NC USA. [Olshan, A. F.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. [Zevallos, J. P.] Univ N Carolina, Dept Otolaryngol Head & Neck Surg, Chapel Hill, NC USA. [Winn, D. M.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Castellsague, X.] Catalan Inst Oncol ICO IDIBELL, Lhospitalet De Llobregat, Spain. [Castellsague, X.] CIBERESP, Madrid, Spain. [Lissowska, J.] M Sklasodowska Curie Mem Canc Ctr & Inst Oncol, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Rudnai, P.] Natl Publ Hlth Ctr, Budapest, Hungary. [Matsuo, K.] Aichi Canc Ctr Res Inst, Div Mol Med, Nagoya, Aichi, Japan. [Morgenstern, H.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Morgenstern, H.] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI USA. [Chen, C.; Vaughan, T. L.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Hofmann, J. N.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [D'Souza, G.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Haddad, R. I.] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. [Lee, Y. -C.; Hashibe, M.] Univ Utah, Sch Med, Dept Family & Prevent Med, Div Publ Hlth, Salt Lake City, UT 84112 USA. [Lee, Y. -C.; Hashibe, M.] Univ Utah, Sch Med, Huntsman Canc Inst, Salt Lake City, UT USA. [La Vecchia, C.] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy. [Boffetta, P.] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA. RP Hashim, D (reprint author), Icahn Sch Med Mt Sinai, Dept Prevent Med, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM dana.hashim@mssm.edu RI Castellsague Pique, Xavier/N-5795-2014; Kowalski, Luiz/D-1701-2012; Curado, Maria Paula/M-6200-2013; Divaris, Kimon/E-4706-2011; OI Castellsague Pique, Xavier/0000-0002-0802-3595; Kowalski, Luiz/0000-0001-5865-9308; Curado, Maria Paula/0000-0001-8172-2483; Divaris, Kimon/0000-0003-1290-7251; La Vecchia, Carlo/0000-0003-1441-897X FU NIH [NCI R03CA113157, R01CA061188, P50CA090388, R01DA011386, R03CA077954, T32CA009142, U01CA096134, R21ES011667, R01CA048996, R01DE012609, R01CA030022, DE016631, R01CA051845]; NIDCR [R03DE016611]; Latin America: Fondo para la Investigacion Cientifica y Tecnologica (FONCYT) Argentina; IMIM (Barcelona); Fundaco de Amparo a Pesquisa no Estado de Sao Paulo (FAPESP) [01/01768-2]; European Commission [IC18-CT97-0222]; National Institute of Environmental Health Sciences [P30ES010126]; NCI, NIH, United States; Fondo de Investigaciones Sanitarias (FIS) of the Spanish Government [FIS 97/0024, FIS 97/0662, BAE 01/5013]; International Union Against Cancer (UICC); Yamagiwa-Yoshida Memorial International Cancer Study Grant; European Commission INCO-COPERNICUS Program [IC15-CT98-0332]; Alper Research Program for Environmental Genomics of the UCLA Jonsson Comprehensive Cancer Center; Ministry of Education, Science, Sports, Culture and Technology of Japan [17015052]; Ministry of Health, Labour and Welfare of Japan [H20-002] FX The INHANCE Consortium was supported by NIH grants NCI R03CA113157 and NIDCR R03DE016611. Studies participating in the pooled analysis were supported by: Latin America: Fondo para la Investigacion Cientifica y Tecnologica (FONCYT) Argentina, IMIM (Barcelona), Fundaco de Amparo a Pesquisa no Estado de Sao Paulo (FAPESP) (No. 01/01768-2), and European Commission (IC18-CT97-0222). North Carolina (1994-1997): NIH (R01CA061188), and in part by a grant from the National Institute of Environmental Health Sciences (P30ES010126). US multicenter: The Intramural Program of the NCI, NIH, United States (No grant number applicable). International Multicenter study: Fondo de Investigaciones Sanitarias (FIS) of the Spanish Government (FIS 97/0024, FIS 97/0662, BAE 01/5013), International Union Against Cancer (UICC), and Yamagiwa-Yoshida Memorial International Cancer Study Grant. Central Europe study: World Cancer Research Fund and the European Commission INCO-COPERNICUS Program (Contract No. IC15-CT98-0332). Los Angeles study: NIH (P50CA090388, R01DA011386, R03CA077954, T32CA009142, U01CA096134, R21ES011667) and the Alper Research Program for Environmental Genomics of the UCLA Jonsson Comprehensive Cancer Center. Japan study: Scientific Research grant from the Ministry of Education, Science, Sports, Culture and Technology of Japan (17015052) and a grant for the ThirdTerm Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labour and Welfare of Japan (H20-002). Seattle study (1985-1995): NIH (R01CA048996, R01DE012609). Seattle-LEO study: NIH (R01CA030022). Puerto Rico study: jointly funded by National Institutes of Health NCI and NIDCR intramural programs (No grant number applicable). Baltimore: NIH (DE016631). Memorial Sloan Kettering Cancer Center, New York, USA: NIH (R01CA051845). HOTSPOT: Johns Hopkins Richard Gelb Cancer Prevention Award (no grant number applicable). NR 38 TC 1 Z9 1 U1 4 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD AUG PY 2016 VL 27 IS 8 BP 1619 EP 1625 DI 10.1093/annonc/mdw224 PG 7 WC Oncology SC Oncology GA DV8JH UT WOS:000383182800034 PM 27234641 ER PT J AU Kasugai, Y Yoshida, N Ohshima, K Matsuo, K Seto, M Tsuzuki, S AF Kasugai, Yumiko Yoshida, Noriaki Ohshima, Koichi Matsuo, Keitaro Seto, Masao Tsuzuki, Shinobu TI New mouse model of acute adult T-cell leukemia generated by transplantation of AKT, BCLxL, and HBZ-transduced T cells SO CANCER SCIENCE LA English DT Article DE AKT; ATL; BCLxL; HBZ; mouse model ID GENE; LEUKEMIA/LYMPHOMA; PROLIFERATION; LYMPHOMA; FEATURES; MICE AB Adult T-cell leukemia/lymphoma (ATL) develops in human T-cell leukemia virus type 1 (HTLV-1) carriers. Although the HTLV-1-encoded HBZ gene is critically involved, HBZ alone is insufficient and additional, cooperative "hits" are required for the development of ATL. Candidate cooperative hits are being defined, but methods to rapidly explore their roles in ATL development in collaboration with HBZ are lacking. Here, we present a new mouse model of acute type ATL that can be generated rapidly by transplanting in vitro-induced T cells that have been retrovirally transduced with HBZ and two cooperative genes, BCLxL and AKT, into mice. Co-transduction of HBZ and BCLxL/AKT allowed these T cells to grow in vitro in the absence of cytokines (Flt3-ligand and interleukin-7), which did not occur with any two-gene combination. Although transplanted T cells were a mixture of cells transduced with different combinations of the genes, tumors that developed in mice were composed of HBZ/BCLxL/AKT triply transduced T cells, showing the synergistic effect of the three genes. The genetic/epigenetic landscape of ATL has only recently been elucidated, and the roles of additional "hits" in ATL pathogenesis remain to be explored. Our model provides a versatile tool to examine the roles of these hits, in collaboration with HBZ, in the development of acute ATL. C1 [Kasugai, Yumiko; Matsuo, Keitaro; Tsuzuki, Shinobu] Aichi Canc Ctr, Res Inst, Div Mol Med, Nagoya, Aichi, Japan. [Yoshida, Noriaki; Ohshima, Koichi; Seto, Masao] Kurume Univ, Sch Med, Dept Pathol, Kurume, Fukuoka, Japan. [Yoshida, Noriaki] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. RP Tsuzuki, S (reprint author), Aichi Canc Ctr, Res Inst, Div Mol Med, Chikusa Ku, 1-1 Kanokoden, Nagoya, Aichi 4648681, Japan. EM stsuzuki@aichi-cc.jp OI Yoshida, Noriaki/0000-0001-7001-0106; Matsuo, Keitaro/0000-0003-1761-6314 FU Ministry of Health, Labor, and Welfare of Japan [H26-Kakushingann-Ippan-010]; Japan Agency for Medical Research and Development [15ck0106015h0102] FX Ministry of Health, Labor, and Welfare of Japan (H26-Kakushingann-Ippan-010); Japan Agency for Medical Research and Development (15ck0106015h0102). NR 19 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1347-9032 EI 1349-7006 J9 CANCER SCI JI Cancer Sci. PD AUG PY 2016 VL 107 IS 8 BP 1072 EP 1078 DI 10.1111/cas.12974 PG 7 WC Oncology SC Oncology GA EB0BU UT WOS:000387009200002 PM 27223899 ER PT J AU Habib, SL Abboud, HE AF Habib, Samy L. Abboud, Hanna E. TI Tuberin regulates reactive oxygen species in renal proximal cells, kidney from rodents, and kidney from patients with tuberous sclerosis complex SO CANCER SCIENCE LA English DT Article DE Kidney; renal cells; reactive oxygen species; tumor suppressor gene; tumorigenesis ID OXIDATIVE DNA-DAMAGE; NADPH-OXIDASE; DIABETIC-NEPHROPATHY; ENDOTHELIAL-CELLS; PROSTATE-CANCER; EXPRESSION; DISEASE; SUPEROXIDE; NOX4; ACTIVATION AB Reactive oxygen species (ROS) are an important endogenous source of DNA damage and oxidative stress in all cell types. Deficiency in tuberin resulted in increased oxidative DNA damage in renal cells. In this study, the role of tuberin in the regulating of ROS and NADPH oxidases was investigated. Formation of ROS and activity of NADPH oxidases were significantly higher in mouse embryonic fibroblasts and in primary culture of rat renal proximal tubular epithelial tuberin-deficient cells compared to wild-type cells. In addition, expression of NADPH oxidase (Nox)1, Nox2, and Nox4 (Nox isoforms) was higher in mouse embryonic fibroblasts and renal proximal tubular epithelial tuberin-deficient cells compared to wild-type cells. Furthermore, activity levels of NADPH oxidases and protein expression of all Nox isoforms were higher in the renal cortex of rat deficient in tuberin. However, treatment of tuberin-deficient cells with rapamycin showed significant decrease in protein expression of all Nox. Significant increase in protein kinase C beta II expression was detected in tuberin-deficient cells, whereas inhibition of protein kinase C beta II by bisindolylmaleimide I resulted in decreased protein expression of all Nox isoforms. In addition, treatment of mice deficient in tuberin with rapamycin resulted in significant decrease in all Nox protein expression. Moreover, protein and mRNA expression of all Nox were highly expressed in tumor kidney tissue of patients with tuberous sclerosis complex compared to control kidney tissue of normal subjects. These data provide the first evidence that tuberin plays a novel role in regulating ROS generation, NADPH oxidase activity, and Nox expression that may potentially be involved in development of kidney tumor in patients with tuberous sclerosis complex. C1 [Habib, Samy L.; Abboud, Hanna E.] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Dept, San Antonio, TX USA. [Habib, Samy L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Abboud, Hanna E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. RP Habib, SL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM habib@uthscsa.edu FU American Heart Association; South Texas Veterans Healthcare System FX American Heart Association; South Texas Veterans Healthcare System. NR 46 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1347-9032 EI 1349-7006 J9 CANCER SCI JI Cancer Sci. PD AUG PY 2016 VL 107 IS 8 BP 1092 EP 1100 DI 10.1111/cas.12984 PG 9 WC Oncology SC Oncology GA EB0BU UT WOS:000387009200004 PM 27278252 ER PT J AU Raciborska, A Bilska, K Weclawek-Tompol, J Ussowicz, M Pogorzala, M Janowska, J Rychlowska-Pruszynska, M Rodriguez-Galindo, C Helwich, E AF Raciborska, Anna Bilska, Katarzyna Weclawek-Tompol, Jadwiga Ussowicz, Marek Pogorzala, Monika Janowska, Joanna Rychlowska-Pruszynska, Magdalena Rodriguez-Galindo, Carlos Helwich, Ewa TI Solid Cancers in the Premature and the Newborn: Report of Three National Referral Centers SO PEDIATRICS AND NEONATOLOGY LA English DT Article DE neonate; perinatal cancer; premature; survival; treatment ID SACROCOCCYGEAL TERATOMA; MESOBLASTIC NEPHROMA; RENAL TUMORS; NEUROBLASTOMA; HEMANGIOPERICYTOMA; INFANTS AB Background: Advances in multidisciplinary care for pediatric cancer have resulted in significant improvement in cure rates over the last decades; however, these advances have not been uniform across all age groups. Cancer is an important cause of perinatal mortality, yet the full spectrum of malignant neoplasms in newborns is not well defined. Methods: The authors have reviewed the clinical features and outcomes of 37 newborns with congenital malignant tumors treated at three referral centers in North, Central, and South Poland between 1980 and 2014. Event-free survival (EFS) and overall survival (OS) rates were estimated by Kaplan-Meier methods and compared using long-rank test and Cox models. Results: Twenty-two patients were diagnosed prenatally. The most common diagnoses were neuroblastoma (48.7%), followed by malignant germ-cell tumor (16.2%), and Wilms' tumor (8.1%). Neuroblastoma was the most common malignancy among full-term infants, and malignant sacrococcygeal teratoma was the most common malignancy in premature infants. Thirty patients (81%) are alive with a median follow-up of 4.8 years from diagnosis. Patients with Wilms' tumor and malignant germ-cell tumors had the best outcomes (5-year OS 100% for both), whereas the worst prognosis was observed for sarcoma patients (5-year OS 72.92%). Premature infants had better outcome than full-term infants (5-year OS 92.8% vs. 72.58%, respectively). Conclusion: Although rare, neonatal cancers can present with an aggressive clinical behavior, but they have a generally good outcome. Early diagnosis and management by expert multidisciplinary teams that integrate perinatal medicine experts with pediatric and surgical oncologists are critical. Centralized care with clear referral pathways that facilitate early initiation of specialized treatment should be prioritized. Copyright (C) 2015, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. C1 [Raciborska, Anna; Bilska, Katarzyna; Rychlowska-Pruszynska, Magdalena] Inst Mother & Child Hlth, Dept Surg Oncol Children & Youth, Ul Kasprzaka 17a, PL-01211 Warsaw, Poland. [Weclawek-Tompol, Jadwiga; Ussowicz, Marek] Wroclaw Med Univ, Dept & Clin Pediat Oncol Hematol & Bone Marrow Tr, Wroclaw, Poland. [Pogorzala, Monika] Nicolaus Copernicus Univ, Dept Pediat Hematol & Oncol, Coll Med, Bydgoszcz, Poland. [Janowska, Joanna; Helwich, Ewa] Inst Mother & Child Hlth, Neonatal Intens Care Unit, Warsaw, Poland. [Rodriguez-Galindo, Carlos] Harvard Med Sch, Dana Farber Canc Inst, Pediat Oncol, Boston, MA USA. [Rodriguez-Galindo, Carlos] Harvard Med Sch, Childrens Hosp, Boston, MA USA. RP Raciborska, A (reprint author), Inst Mother & Child Hlth, Dept Surg Oncol Children & Youth, Ul Kasprzaka 17a, PL-01211 Warsaw, Poland. EM anna.raciborska@hoga.pl NR 22 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER TAIWAN PI TAIPEI PA RM N-412, 4F, CHIA HSIN BUILDING 11, NO 96, ZHONG SHAN N ROAD SEC 2, TAIPEI, 10449, TAIWAN SN 1875-9572 J9 PEDIATR NEONATOL JI Pediatr. Neonatol. PD AUG PY 2016 VL 57 IS 4 BP 295 EP 301 DI 10.1016/j.pedneo.2015.08.007 PG 7 WC Pediatrics SC Pediatrics GA EA9UP UT WOS:000386990500007 PM 26934827 ER PT J AU Liang, JS Lee, SP Pulli, B Chen, JW Kao, SC Tsang, YM Hsieh, KLC AF Liang, Jao-Shwann Lee, Shiou-Ping Pulli, Benjamin Chen, John W. Kao, Sheng-Chuan Tsang, Yuk-Ming Hsieh, Kevin Li-Chun TI Microstructural Changes in Absence Seizure Children: A Diffusion Tensor Magnetic Resonance Imaging Study SO PEDIATRICS AND NEONATOLOGY LA English DT Article DE absence seizures; diffusion tensor imaging; magnetic resonance imaging; mean diffusivity; tractography ID SPIKE-WAVE SEIZURES; GENERALIZED PENICILLIN EPILEPSY; CORPUS-CALLOSUM; FIBER TRACTOGRAPHY; WAG/RIJ RATS; OPTIC-NERVE; MRI; DISCHARGES; BRAIN; ABNORMALITIES AB Background: Absence seizures are a subtype of epileptic seizures clinically characterized by transient alterations in states of consciousness and by electroencephalography indicating diffuse spike-wave discharges (SWD). Conventional brain magnetic resonance imaging (MRI) is not routinely used to establish the diagnosis, but rather to rule out other diseases. The present study investigated tissue integrity in children with SWD epilepsy using diffusion tensor imaging (DTI). Methods: Magnetic resonance imaging (MRI)-DTI was conducted in 18 patients with absence seizures and 10 control participants. Brain areas were evaluated using diffusion maps, and fractional anisotropy (FA), mean diffusivity (MD), parallel diffusivity (lambda parallel to), and perpendicular diffusivity (lambda perpendicular to) values were extracted and analyzed. Tractography at the regions of abnormal diffusion indices was then reconstructed in each group, and tract symmetry was evaluated by an index of asymmetry (AI). Statistical analyses were performed using nonparametric Mann-Whitney U tests, with p values < 0.05 indicating statistical significance. Results: Compared to the control group, patients with SWD epilepsy had lower FA values and higher MD values at the genu of the corpus callosum. There was also a stronger negative correlation between MD and FA values at the genu of the corpus callosum in patients than in control participants. The AI for the fiber tracts through the genu of the corpus callosum in the SWD group was significantly higher than that of the control group, indicating that tract distribution was more asymmetric in patients with epilepsy. There were no significant differences between groups in diffusion indices for other brain areas. Conclusion: We observed microstructural changes in the genu of the corpus callosum, as well as reduced FA values, increased lambda perpendicular to values, increased MD values, and asymmetric distribution of fiber tracts, indicating that DTI is more sensitive than conventional MRI to detect brain abnormalities in children with absence seizures. Copyright (C) 2015, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. C1 [Liang, Jao-Shwann] Far Eastern Mem Hosp, Dept Pediat, New Taipei, Taiwan. [Lee, Shiou-Ping] Far Eastern Mem Hosp, Div Med Imaging, Dept Radiol, New Taipei, Taiwan. [Pulli, Benjamin; Chen, John W.; Kao, Sheng-Chuan; Tsang, Yuk-Ming] Harvard Med Sch, Ctr Syst Biol, Massachusetts Gen Hosp, Boston, MA USA. [Pulli, Benjamin; Chen, John W.; Kao, Sheng-Chuan; Tsang, Yuk-Ming] Harvard Med Sch, Dept Radiol, Massachusetts Gen Hosp, Boston, MA USA. [Hsieh, Kevin Li-Chun] Taipei Med Univ Hosp, Dept Med Imaging, 252,Wu Hsing St, Taipei 110, Taiwan. [Hsieh, Kevin Li-Chun] Taipei Med Univ, Coll Med, Translat Imaging Res Ctr, Taipei, Taiwan. RP Hsieh, KLC (reprint author), Taipei Med Univ Hosp, Dept Med Imaging, 252,Wu Hsing St, Taipei 110, Taiwan. EM Kevinh9396@gmail.com NR 40 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER TAIWAN PI TAIPEI PA RM N-412, 4F, CHIA HSIN BUILDING 11, NO 96, ZHONG SHAN N ROAD SEC 2, TAIPEI, 10449, TAIWAN SN 1875-9572 J9 PEDIATR NEONATOL JI Pediatr. Neonatol. PD AUG PY 2016 VL 57 IS 4 BP 318 EP 325 DI 10.1016/j.pedneo.2015.10.003 PG 8 WC Pediatrics SC Pediatrics GA EA9UP UT WOS:000386990500010 PM 26750405 ER PT J AU Funk, LM Jolles, SA Voils, CI AF Funk, Luke M. Jolles, Sally A. Voils, Corrine I. TI Obesity as a disease: has the AMA resolution had an impact on how physicians view obesity? SO SURGERY FOR OBESITY AND RELATED DISEASES LA English DT Editorial Material DE Health services; Obesity; Public health ID BARIATRIC SURGERY; WEIGHT BIAS; CARE AB Background: In 2013, the American Medical Association (AMA) passed a resolution characterizing obesity as a disease. It is unclear whether primary care physicians (PCPs) agree with this characterization and how their agreement or lack thereof affects their treatment of patients with obesity. Objectives: We sought to understand PCP opinions about the AMA obesity resolution and how it has affected management of patients with obesity. Setting: Small, medium, and large communities in Wisconsin Methods: Focus groups were conducted with PCPs in Wisconsin. PCPs were asked whether they considered obesity a disease and what they factored into this consideration, including the AMA decision. A directed approach to content analysis was used to analyze the data. A taxonomy of consensus codes was developed, coding summaries were generated, and representative quotes were identified. Results: Three focus groups comprising a total of 16 PCP participants were conducted. Not all PCPs were aware of the AMA resolution. PCPs held divergent opinions on whether obesity represented a disease, primarily focusing their considerations on obesity as a risk factor versus a disease. They also discussed how considering obesity as a disease affects the patient doctor relationship, insurance coverage, physician reimbursement, and research. Conclusion: The AMA resolution did not appear to have made a significant impact on PCP opinions or management practices in our focus groups in Wisconsin. Follow-up surveys that quantify the prevalance of these opinions and practices at the state and national levels would be highly informative. (Surg Obes Relat Dis 2016;12:1431-1435.) Published by Elsevier Inc. on behalf of American Society for Metabolic and Bariatric Surgery. C1 [Funk, Luke M.; Jolles, Sally A.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Funk, Luke M.; Jolles, Sally A.] Univ Wisconsin, Dept Surg, Wisconsin Surg Outcomes Res Program WiSOR, Sch Med & Publ Hlth, Madison, WI USA. [Voils, Corrine I.] Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Voils, Corrine I.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. RP Funk, LM (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, 600 Highland Ave,H4-728 Clin Sci Ctr, Madison, WI 53792 USA. EM funk@surgery.wisc.edu NR 14 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 1550-7289 EI 1878-7533 J9 SURG OBES RELAT DIS JI Surg. Obes. Relat. Dis. PD AUG PY 2016 VL 12 IS 7 BP 1431 EP 1435 DI 10.1016/j.soard.2016.05.009 PG 5 WC Surgery SC Surgery GA EA9TJ UT WOS:000386987300031 PM 27444860 ER PT J AU Decker, BK Harris, PL Muder, RR Hong, JH Singh, N Sonel, AF Clancy, CJ AF Decker, Brooke K. Harris, Patricia L. Muder, Robert R. Hong, Jae H. Singh, Nina Sonel, Ali F. Clancy, Cornelius J. TI Improving the Diagnosis of Legionella Pneumonia within a Healthcare System through a Systematic Consultation and Testing Program SO ANNALS OF THE AMERICAN THORACIC SOCIETY LA English DT Article AB Rationale: Legionella testing is not recommended for all patients with pneumonia, but rather for particular patient subgroups. As a result, the overall incidence of Legionella pneumonia may be underestimated. Objectives: To determine the incidence of Legionella pneumonia in a veteran population in an endemic area after introduction of a systematic infectious diseases consultation and testing program. Methods: In response to a 2011-2012 outbreak, the VA Pittsburgh Healthcare System mandated infectious diseases consultations and testing for Legionella by urine antigen and sputum culture in all patients with pneumonia. Measurements and Main Results: Between January 2013 and December 2015, 1,579 cases of pneumonia were identified. The incidence of pneumonia was 788/100,000 veterans per year, including 352/100,000 veterans per year and 436/100,000 veterans per year with community-associated pneumonia (CAP) and health care-associated pneumonia, respectively. Ninety-eight percent of patients with suspected pneumonia were tested for Legionella by at least one method. Legionella accounted for 1% of pneumonia cases (n = 16), including 1.7% (12/706) and 0.6% (4/873) of CAP and health care-associated pneumonia, respectively. The yearly incidences of Legionella pneumonia and Legionella CAP were 7.99 and 5.99/100,000 veterans, respectively. The sensitivities of urine antigen and sputum culture were 81% and 60%, respectively; the specificity of urine antigen was >99.97%. Urine antigen testing and Legionella cultures increased by 65% and 330%, respectively, after introduction of our program. Conclusions: Systematic testing of veterans in an endemic area revealed a higher incidence of Legionella pneumonia and CAP than previously reported. Widespread urine antigen testing was not limited by false positivity. C1 [Decker, Brooke K.; Hong, Jae H.; Singh, Nina; Clancy, Cornelius J.] Infect Dis Sect, Pittsburgh, PA USA. [Harris, Patricia L.; Sonel, Ali F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Decker, Brooke K.; Muder, Robert R.; Hong, Jae H.; Singh, Nina; Clancy, Cornelius J.] Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA USA. RP Decker, BK (reprint author), VA Pittsburgh Healthcare Syst, Infect Dis Sect, Univ Dr C ID Sect,111E-U, Pittsburgh, PA 15240 USA. EM brooke.decker@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1546-3222 EI 2325-6621 J9 ANN AM THORAC SOC JI Ann. Am. Thoracic Society PD AUG PY 2016 VL 13 IS 8 BP 1289 EP 1293 DI 10.1513/AnnalsATS.201510-715BC PG 5 WC Respiratory System SC Respiratory System GA DZ8JV UT WOS:000386117600019 PM 27243279 ER PT J AU Berning, JN Poor, AD Buckley, SM Patel, KR Lederer, DJ Goldstein, NE Brodie, D Baldwin, MR AF Berning, Joel N. Poor, Armeen D. Buckley, Sarah M. Patel, Komal R. Lederer, David J. Goldstein, Nathan E. Brodie, Daniel Baldwin, Matthew R. TI A Novel Picture Guide to Improve Spiritual Care and Reduce Anxiety in Mechanically Ventilated Adults in the Intensive Care Unit SO ANNALS OF THE AMERICAN THORACIC SOCIETY LA English DT Article AB Rationale: Hospital chaplains provide spiritual care that helps patients facing serious illness cope with their symptoms and prognosis, yet because mechanically ventilated patients cannot speak, spiritual care of these patients has been limited. Objectives: To determine the feasibility and measure the effects of chaplain-led picture-guided spiritual care for mechanically ventilated adults in the intensive care unit (ICU). Methods: We conducted a quasi-experimental study at a tertiary care hospital between March 2014 and July 2015. Fifty mechanically ventilated adults in medical or surgical ICUs without delirium or dementia received spiritual care by a hospital chaplain using an illustrated communication card to assess their spiritual affiliations, emotions, and needs and were followed until hospital discharge. Feasibility was assessed as the proportion of participants able to identify spiritual affiliations, emotions, and needs using the card. Among the first 25 participants, we performed semistructured interviews with 8 ICU survivors to identify how spiritual care helped them. For the subsequent 25 participants, we measured anxiety (on 100-mm visual analog scales [VAS]) immediately before and after the first chaplain visit, and we performed semistructured interviews with 18 ICU survivors with added measurements of pain and stress (on +/- 100-mm VAS). Measurements and Main Results: The mean (SD) age was 59 (+/- 16) years, median mechanical ventilation days was 19.5 (interquartile range, 7-29 d), and 15 (30%) died in-hospital. Using the card, 50 (100%) identified a spiritual affiliation, 47 (94%) identified one or more emotions, 45 (90%) rated their spiritual pain, and 36 (72%) selected a chaplain intervention. Anxiety after the first visit decreased 31% (mean score change, -20; 95% confidence interval, -33 to -7). Among 28 ICU survivors, 26 (93%) remembered the intervention and underwent semistructured interviews, of whom 81% felt more capable of dealing with their hospitalization and 0% felt worse. The 18 ICU survivors who underwent additional VAS testing during semistructured follow-up interviews reported a 49-point reduction in stress (95% confidence interval, -72 to -24) and no significant change in physical pain that they attributed to picture-guided spiritual care. Conclusions: Chaplain-led picture-guided spiritual care is feasible among mechanically ventilated adults and shows potential for reducing anxiety during and stress after an ICU admission. C1 [Berning, Joel N.] NewYork Presbyterian Hosp, Pastoral Care & Educ Dept, New York, NY USA. [Poor, Armeen D.; Buckley, Sarah M.; Patel, Komal R.; Lederer, David J.; Brodie, Daniel; Baldwin, Matthew R.] Columbia Univ, Coll Phys & Surg, Div Pulm Allergy & Crit Care, New York, NY USA. [Lederer, David J.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. [Goldstein, Nathan E.] Icahn Sch Med Mt Sinai, Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Goldstein, Nathan E.] James J Peters VA Med Ctr, Geriatr Res Educ & Clin Ctr, New York, NY USA. RP Baldwin, MR (reprint author), Div Pulm Allergy & Crit Care, 622 West 168th St,PH-8E Room 101, New York, NY 10032 USA. EM mrb45@cumc.columbia.edu FU National Institutes of Health [UL1 TR000040, KL2 TR000081, K23AG045560] FX Supported by National Institutes of Health grants UL1 TR000040, KL2 TR000081, and K23AG045560. The views expressed in this article do not communicate an official position of National Institutes of Health. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1546-3222 EI 2325-6621 J9 ANN AM THORAC SOC JI Ann. Am. Thoracic Society PD AUG PY 2016 VL 13 IS 8 BP 1333 EP 1342 DI 10.1513/AnnalsATS.201512-831OC PG 10 WC Respiratory System SC Respiratory System GA DZ8JV UT WOS:000386117600025 PM 27097049 ER PT J AU Kamdar, BB Knauert, MP Jones, SF Parsons, EC Parthasarathy, S Pisani, MA AF Kamdar, Biren B. Knauert, Melissa P. Jones, Shirley F. Parsons, Elizabeth C. Parthasarathy, Sairam Pisani, Margaret A. CA Sleep ICU SLEEPii Task Force TI Perceptions and Practices Regarding Sleep in the Intensive Care Unit A Survey of 1,223 Critical Care Providers SO ANNALS OF THE AMERICAN THORACIC SOCIETY LA English DT Article AB Rationale: Poor sleep affects a majority of critically ill patients and is believed to be associated with adverse intensive care unit (ICU) outcomes such as delirium. While recent guidelines recommend sleep promotion efforts to improve delirium and other ICU outcomes, little is known about critical care providers' beliefs regarding sleep in the ICU. Objectives: To evaluate providers' perceptions and practices regarding sleep in the ICU. Methods: From April to July 2014, the Sleep in the ICU Survey was disseminated to ICU providers via institutional e-mail lists and four international critical care society distribution lists. Measurements and Main Results: A total of 1,223 surveys were completed by providers from 24 countries. Respondents were primarily nurses (59%) or physicians (39%). Most respondents indicated that ICU patients experienced " poor" or " very poor" sleep 75%) and that poor sleep could affect the ICU recovery process (88%). Respondents also felt that poor sleep was associated with negative ICU outcomes such as the development of delirium (97%), longer length of stay (88%), poor participation in physical therapy (87%), and delayed liberation from mechanical ventilation (83%). The minority (32%) of providers had sleep-promoting protocols; these providers tended to believe their patients slept longer and experienced better sleep quality. Conclusions: Though most clinicians believe that sleep in the ICU is poor and adversely affects patient outcomes, a minority of the ICUs represented by our respondents have sleep promotion protocols. These findings highlight discordant provider perceptions and practices surrounding sleep in the ICU, as well as a possible lack of available evidence-based guidelines for promoting sleep in the ICU. C1 [Kamdar, Biren B.] Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med, 10833 Le Conte Ave,Room 37-131 CHS, Los Angeles, CA 90095 USA. [Knauert, Melissa P.; Pisani, Margaret A.] Yale Univ, Sch Med, Sect Pulm Crit Care & Sleep Med, New Haven, CT USA. [Jones, Shirley F.] Texas A&M Hlth Sci Ctr Coll Med, Baylor Scott & White Healthcare, Div Pulm Crit Care & Sleep Med, Temple, TX USA. [Parsons, Elizabeth C.] Univ Washington, Div Pulm & Crit Care Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Parthasarathy, Sairam] Univ Arizona, Div Pulm & Crit Care Med, Tucson, AZ USA. RP Kamdar, BB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med, 10833 Le Conte Ave,Room 37-131 CHS, Los Angeles, CA 90095 USA. EM bkamdar@mednet.ucla.edu OI Kamdar, Biren/0000-0002-9245-6229 FU UCLA Clinical and Translational Science Institute (CTSI) National Institutes of Health (NIH)/National Center for Advancing Translational Sciences (NCATS) [UCLA UL1TR000124]; Yale Claude D. Pepper Older Americans Independence Center [P30AG021342]; NIH/NCATS [KL2 TR000140] FX B.B.K. is currently supported by a Career Development Award from the UCLA Clinical and Translational Science Institute (CTSI) National Institutes of Health (NIH)/National Center for Advancing Translational Sciences (NCATS) (UCLA UL1TR000124). M.P.K. is currently supported by a Career Development Award from the Yale Claude D. Pepper Older Americans Independence Center (P30AG021342) and by a CTSA grant from the NIH/NCATS (KL2 TR000140). The views expressed here are those of the authors and do not reflect the position or policy of the Department of Veterans Affairs. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1546-3222 EI 2325-6621 J9 ANN AM THORAC SOC JI Ann. Am. Thoracic Society PD AUG PY 2016 VL 13 IS 8 BP 1370 EP 1377 DI 10.1513/AnnalsATS.201601-087OC PG 8 WC Respiratory System SC Respiratory System GA DZ8JV UT WOS:000386117600029 PM 27104770 ER PT J AU Cardet, JC Ash, S Kusa, T Camargo, CA Israel, E AF Cardet, Juan Carlos Ash, Samuel Kusa, Tope Camargo, Carlos A., Jr. Israel, Elliot TI Insulin resistance modifies the association between obesity and current asthma in adults SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article ID BODY-MASS INDEX; METABOLIC SYNDROME; UNITED-STATES; SELECTIVE INSULIN; PREVALENCE; COHORT; AIRWAY; LUNG; IDENTIFICATION; INFLAMMATION AB Insulin resistance potentiates the association between obesity and childhood asthma, but this relationship appears inconsistent in relatively small studies of adults. We investigated effect modification in adults using the National Health and Nutrition Examination Survey 2003-2012, a large, nationally representative database. Insulin resistance and a history of physician-diagnosed current asthma were obtained from 12 421 adults, ages 18-85 years. We used logistic regression to determine associations between obesity and current asthma, adjusting for age, sex, race/ethnicity, poverty income ratio and smoking status. An interaction term evaluated effect modification by insulin resistance of the obesity-asthma association. As expected, obesity was positively associated with current asthma. Insulin resistance modified this association, with obesity measured as body mass index, waist circumference or waist-to-height ratio. The relationship between obesity and current asthma was stronger with increasing insulin resistance tertiles (OR 2.05, 95% CI 2.76-3.00; p-value for interaction 0.03). This association was robust to adjustments for other components of the metabolic syndrome (hypertriglyceridaemia, hypertension, hyperglycaemia and systemic inflammation). None of these components were themselves effect modifiers of the obesity-asthma association. In this large, nationally representative sample, insulin resistance modified the association between obesity and current asthma in adults. Targeting insulin resistance may represent a novel therapeutic strategy for obese patients with asthma. C1 [Cardet, Juan Carlos; Israel, Elliot] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, 75 Francis St, Boston, MA 02115 USA. [Cardet, Juan Carlos; Ash, Samuel; Israel, Elliot] Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA. [Kusa, Tope] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Israel, E (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM eisrael@partners.org FU National Institute of Allergy and Infectious Diseases, a National Institutes of Health Diversity Supplement [3U19AI095219-04S1]; [U19AI095219-01] FX This work was supported by grants from the National Institute of Allergy and Infectious Diseases, a National Institutes of Health Diversity Supplement (3U19AI095219-04S1), and funds from centre grant U19AI095219-01 to J.C. Cardet. Funding information for this article has been deposited with FundRef. NR 37 TC 3 Z9 3 U1 1 U2 1 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 EI 1399-3003 J9 EUR RESPIR J JI Eur. Resp. J. PD AUG PY 2016 VL 48 IS 2 BP 403 EP 410 DI 10.1183/13993003.00246-2016 PG 8 WC Respiratory System SC Respiratory System GA DZ6FQ UT WOS:000385957400018 PM 27103388 ER PT J AU Tabung, FK Smith-Warner, SA Chavarro, JE Wu, K Fuchs, CS Hu, FB Chan, AT Willett, WC Giovannucci, EL AF Tabung, Fred K. Smith-Warner, Stephanie A. Chavarro, Jorge E. Wu, Kana Fuchs, Charles S. Hu, Frank B. Chan, Andrew T. Willett, Walter C. Giovannucci, Edward L. TI Development and Validation of an Empirical Dietary Inflammatory Index SO JOURNAL OF NUTRITION LA English DT Article DE hypothesis-driven; dietary patterns; dietary inflammatory potential; inflammatory markers; inflammation ID FOOD-FREQUENCY QUESTIONNAIRE; C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; TOTAL-ENERGY INTAKE; COLORECTAL-CANCER; NUTRITIONAL EPIDEMIOLOGY; POSTMENOPAUSAL WOMEN; ENDOTHELIAL DYSFUNCTION; SYSTEMIC INFLAMMATION; PLASMA-CONCENTRATIONS AB Background: Knowledge on specific biological pathways mediating disease occurrence (e.g., inflammation) may be utilized to construct hypotheses-driven dietary patterns that take advantage of current evidence on disease-related hypotheses and the statistical methods of a posteriori patterns. Objective: We developed and validated an empirical dietary inflammatory index (EDII) based on food groups. Methods: We entered 39 pre-defined food groups in reduced rank regression models followed by stepwise linear regression analyses in the Nurses' Health Study (NHS, n = 5230) to identify a dietary pattern most predictive of 3 plasma inflammatory markers: interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor a receptor 2 (TNF alpha R2). We evaluated the construct validity of the EDII in 2 independent samples from NHS-II (n = 1002) and Health Professionals Follow-up Study (HPFS, n = 2632) using multivariable-adjusted linear regression models to examine how well the EDII predicted concentrations of IL-6, CRP, TNFaR2, adiponectin, and an overall inflammatory marker score combining all biomarkers. Results: The EDII is the weighted sum of 18 food groups; 9 are anti-inflammatory and 9 proinflammatory. In NHS-II and HPFS, the EDII significantly predicted concentrations of all biomarkers. For example, the relative concentrations comparing extreme EDII quintiles in NHS-II were: adiponectin, 0.88 (95% CI, 0.80, 0.96), P-trend = 0.003; and CRP, 1.52 (95% CI, 1.18, 1.97), P-trend = 0.002. Corresponding associations in HPFS were: 0.87 (95% CI, 0.82, 0.92), P-trend < 0.0001; and 1.23 (95% CI, 1.09, 1.40), P-trend = 0.002. Conclusion: The EDII represents, to our knowledge, a novel, hypothesis-driven, empirically derived dietary pattern that assesses diet quality based on its inflammatory potential. Its strong construct validity in independent samples of women and men indicates its usefulness in assessing the inflammatory potential of whole diets. Additionally, the EDII may be calculated in a standardized and reproducible manner across different populations thus circumventing a major limitation of dietary patterns derived from the same study in which they are applied. C1 [Tabung, Fred K.; Smith-Warner, Stephanie A.; Chavarro, Jorge E.; Wu, Kana; Hu, Frank B.; Willett, Walter C.; Giovannucci, Edward L.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Tabung, Fred K.; Smith-Warner, Stephanie A.; Chavarro, Jorge E.; Hu, Frank B.; Willett, Walter C.; Giovannucci, Edward L.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Chavarro, Jorge E.; Fuchs, Charles S.; Hu, Frank B.; Chan, Andrew T.; Willett, Walter C.; Giovannucci, Edward L.] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Chavarro, Jorge E.; Fuchs, Charles S.; Hu, Frank B.; Willett, Walter C.; Giovannucci, Edward L.] Harvard Med Sch, Dept Med, Boston, MA USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA 02114 USA. RP Tabung, FK (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.; Tabung, FK (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. EM ftabung@hsph.harvard.edu FU NIH [P30DK046200, U54 CA155426, UM1 CA 167552, UM1 CA 186107, UM1 CA 176726] FX JEC and FBH were supported by NIH grants P30DK046200 and U54 CA155426. The Health Professionals Follow- Up Study, Nurses' Health Study, and Nurses Health Study II cohorts are supported by NIH grants UM1 CA 167552, UM1 CA 186107, and UM1 CA 176726, respectively. NR 64 TC 3 Z9 3 U1 11 U2 11 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 EI 1541-6100 J9 J NUTR JI J. Nutr. PD AUG PY 2016 VL 146 IS 8 BP 1560 EP 1570 DI 10.3945/jn.115.228718 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DZ8OT UT WOS:000386130900013 PM 27358416 ER PT J AU Goulet, JL Kerns, RD Bair, M Becker, WC Brennan, P Burgess, DJ Carroll, CM Dobscha, S Driscoll, MA Fenton, BT Fraenkel, L Haskell, SG Heapy, AA Higgins, DM Hoff, RA Hwang, U Justice, AC Piette, JD Sinnott, P Wandner, L Womack, JA Brandt, CA AF Goulet, Joseph L. Kerns, Robert D. Bair, Matthew Becker, William C. Brennan, Penny Burgess, Diana J. Carroll, Constance M. Dobscha, Steven Driscoll, Mary A. Fenton, Brenda T. Fraenkel, Liana Haskell, Sally G. Heapy, Alicia A. Higgins, Diana M. Hoff, Rani A. Hwang, Ula Justice, Amy C. Piette, John D. Sinnott, Patsi Wandner, Laura Womack, Julie A. Brandt, Cynthia A. TI The musculoskeletal diagnosis cohort: examining pain and pain care among veterans SO PAIN LA English DT Article DE Pain; Musculoskeletal disorders; Mental health comorbidity; Cohort studies; Veterans; Epidemiology ID LOW-BACK-PAIN; IRAQI FREEDOM; SYSTEM; COMORBIDITY; DEPRESSION; FREEDOM/OPERATION; TRANSFORMATION; PREVALENCE; DISORDERS; TRENDS AB Musculoskeletal disorders (MSDs) are highly prevalent, painful, and costly disorders. The MSD Cohort was created to characterize variation in pain, comorbidities, treatment, and outcomes among patients with MSD receiving Veterans Health Administration care across demographic groups, geographic regions, and facilities. We searched electronic health records to identify patients treated in Veterans Health Administration who had ICD-9-CM codes for diagnoses including, but not limited to, joint, back, and neck disorders, and osteoarthritis. Cohort inclusion criteria were 2 or more outpatient visits occurring within 18 months of one another or one inpatient visit with an MSD diagnosis between 2000 and 2011. The first diagnosis is the index date. Pain intensity numeric rating scale (NRS) scores, comorbid medical and mental health diagnoses, pain-related treatments, and other characteristics were collected retrospectively and prospectively. The cohort included 5,237,763 patients; their mean age was 59, 6% were women, 15% identified as black, and 18% reported severe pain (NRS >= 7) on the index date. Nontraumatic joint disorder (27%), back disorder (25%), and osteoarthritis (21%) were the most common MSD diagnoses. Patients entering the cohort in recent years had more concurrent MSD diagnoses and higher NRS scores. The MSD Cohort is a rich resource for collaborative pain-relevant health service research. C1 [Goulet, Joseph L.; Kerns, Robert D.; Becker, William C.; Carroll, Constance M.; Driscoll, Mary A.; Fenton, Brenda T.; Fraenkel, Liana; Haskell, Sally G.; Heapy, Alicia A.; Hoff, Rani A.; Justice, Amy C.; Wandner, Laura; Womack, Julie A.; Brandt, Cynthia A.] VA Connecticut Healthcare Syst, Pain Res Informat Multimorbid & Educ Ctr PRIME, 950 Campbell Ave,35a, West Haven, CT 06516 USA. [Bair, Matthew] Richard L Roudebush VAMC, VA Ctr Hlth Informat & Commun, Indianapolis, IN USA. [Brennan, Penny] VA Palo Alto Hlth Care Syst, HSR&D Ctr Innovat Implementat, Palo Alto, CA USA. [Burgess, Diana J.] Minneapolis Vet Affairs Healthcare Syst, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Dobscha, Steven] VA Portland Hlth care Syst, Ctr Improve Veteran Involvement Care CIVIC, Portland, OR USA. [Higgins, Diana M.] VA Boston Healthcare Syst, Anesthesiol Crit Care & Pain Med Service, Res Serv, Boston, MA USA. [Hwang, Ula] James J Peters VAMC, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Piette, John D.] VA Ann Arbor Healthcare Syst, VA Ctr Clin Management Res, Ann Arbor, MI USA. [Sinnott, Patsi] VA Palo Alto Hlth Care Syst, Hlth Econ Resource Ctr, Menlo Pk, CA USA. RP Goulet, JL (reprint author), VA Connecticut Healthcare Syst, 950 Campbell Ave,35a, West Haven, CT 06516 USA. EM joseph.goulet@va.gov OI Goulet, Joseph/0000-0002-0842-804X FU Veterans Health Administration Health Services Research Development [CREATE 12-012, CIN 13-407] FX This work was supported by the Veterans Health Administration Health Services Research & Development grants CREATE 12-012 (Kerns, Goulet, and Brandt Primary Investigators) and CIN 13-407 (Kerns Primary Investigator). NR 39 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD AUG PY 2016 VL 157 IS 8 BP 1696 EP 1703 DI 10.1097/j.pain.0000000000000567 PG 8 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA DZ7AB UT WOS:000386014000018 PM 27023420 ER PT J AU Beavers, WN Skaar, EP AF Beavers, William N. Skaar, Eric P. TI Neutrophil-generated oxidative stress and protein damage in Staphylococcus aureus SO PATHOGENS AND DISEASE LA English DT Review DE Staphylococcus aureus; oxidative stress; neutrophils; protein oxidation; antioxidant defenses; host-pathogen interface ID NITRIC-OXIDE SYNTHASE; SMALL-COLONY VARIANTS; HYDROPEROXIDE REDUCTASE AHPC; REPRESSES BIOFILM FORMATION; PEROXIDE-CHLORIDE SYSTEM; HYPOCHLOROUS ACID; HYDROGEN-PEROXIDE; SUPEROXIDE-DISMUTASE; TYROSINE NITRATION; BACILLUS-SUBTILIS AB Staphylococcus aureus is a ubiquitous, versatile and dangerous pathogen. It colonizes over 30% of the human population, and is one of the leading causes of death by an infectious agent. During S. aureus colonization and invasion, leukocytes are recruited to the site of infection. To combat S. aureus, leukocytes generate an arsenal of reactive species including superoxide, hydrogen peroxide, nitric oxide and hypohalous acids that modify and inactivate cellular macromolecules, resulting in growth defects or death. When S. aureus colonization cannot be cleared by the immune system, antibiotic treatment is necessary and can be effective. Yet, this organism quickly gains resistance to each new antibiotic it encounters. Therefore, it is in the interest of human health to acquire a deeper understanding of how S. aureus evades killing by the immune system. Advances in this field will have implications for the design of future S. aureus treatments that complement and assist the host immune response. In that regard, this review focuses on how S. aureus avoids host-generated oxidative stress, and discusses the mechanisms used by S. aureus to survive oxidative damage including antioxidants, direct repair of damaged proteins, sensing oxidant stress and transcriptional changes. This review will elucidate areas for studies to identify and validate future antimicrobial targets. C1 [Beavers, William N.; Skaar, Eric P.] Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, US Dept Vet Affairs,Vanderbilt Inst Chem Biol,Med, 1161 21st Ave South, Nashville, TN 37232 USA. [Skaar, Eric P.] Vanderbilt Univ, Sch Med, Tennessee Valley Healthcare Syst, US Dept Vet Affairs,Vanderbilt Inst Chem Biol, 1161 21st Ave S, Nashville, TN 37232 USA. RP Skaar, EP (reprint author), Vanderbilt Univ, Dept Microbiol & Immunol, 1161 21st Ave South, Nashville, TN 37232 USA. EM eric.skaar@vanderbilt.edu FU National Institutes of Health [T32 AI007474 21, R01 AI069233, R01 AI73843] FX The writing of this manuscript was supported by the National Institutes of Health through fellowships to WNB (T32 AI007474 21) and research grants to EPS (R01 AI069233 and R01 AI73843). NR 153 TC 1 Z9 1 U1 5 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 2049-632X J9 PATHOG DIS JI Pathog. Dis. PD AUG PY 2016 VL 74 IS 6 AR ftw060 DI 10.1093/femspd/ftw060 PG 15 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DY3UG UT WOS:000385019700008 ER PT J AU Falvey, JR Burke, RE Malone, D Ridgeway, KJ McManus, BM Stevens-Lapsley, JE AF Falvey, Jason R. Burke, Robert E. Malone, Daniel Ridgeway, Kyle J. McManus, Beth M. Stevens-Lapsley, Jennifer E. TI Role of Physical Therapists in Reducing Hospital Readmissions: Optimizing Outcomes for Older Adults During Care Transitions From Hospital to Community SO PHYSICAL THERAPY LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; LOW-INCOME SENIORS; LENGTH-OF-STAY; FUNCTIONAL STATUS; HEART-FAILURE; DISCHARGE SUMMARIES; 30-DAY READMISSION; GAIT SPEED; HOME; RISK AB Hospital readmissions in older adult populations are an emerging quality indicator for acute care hospitals. Recent evidence has linked functional decline during and after hospitalization with an elevated risk of hospital readmission. However, models of care that have been developed to reduce hospital readmission rates do not adequately address functional deficits. Physical therapists, as experts in optimizing physical function, have a strong opportunity to contribute meaningfully to care transition models and demonstrate the value of physical therapy interventions in reducing readmissions. Thus, the purposes of this perspective article are: (1) to describe the need for physical therapist input during care transitions for older adults and (2) to outline strategies for expanding physical therapy participation in care transitions for older adults, with an overall goal of reducing avoidable 30-day hospital readmissions. C1 [Falvey, Jason R.; Malone, Daniel; Ridgeway, Kyle J.; Stevens-Lapsley, Jennifer E.] Univ Colorado Anschutz Med Campus, Dept Phys Med & Rehabil, Phys Therapy Program, Mail Stop C244,13121 East 17th Ave,Room 3116, Aurora, CO 80045 USA. [Falvey, Jason R.] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. [Burke, Robert E.] Univ Colorado Anschutz Med Campus, Res & Hosp Med Sect, Denver VA Med Ctr, Aurora, CO USA. [Burke, Robert E.] Univ Colorado Anschutz Med Campus, Dept Med, Aurora, CO USA. [Ridgeway, Kyle J.] Univ Colorado Hosp, Aurora, CO USA. [McManus, Beth M.] Univ Colorado Anschutz Med Campus, Sch Publ Hlth, Dept Hlth Syst Management & Policy, Aurora, CO USA. [Stevens-Lapsley, Jennifer E.] Vet Affairs Geriatr Res Educ & Clin Ctr, Denver, CO USA. RP Falvey, JR (reprint author), Univ Colorado Anschutz Med Campus, Dept Phys Med & Rehabil, Phys Therapy Program, Mail Stop C244,13121 East 17th Ave,Room 3116, Aurora, CO 80045 USA.; Falvey, JR (reprint author), Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. EM Jason.Falvey@ucdenver.edu FU NICHD NIH HHS [K12 HD055931] NR 66 TC 1 Z9 1 U1 1 U2 1 PU AMER PHYSICAL THERAPY ASSOC PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 USA SN 0031-9023 EI 1538-6724 J9 PHYS THER JI Phys. Ther. PD AUG PY 2016 VL 96 IS 8 BP 1124 EP 1133 DI 10.2522/ptj.20150526 PG 10 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA DZ9AQ UT WOS:000386165800002 PM 26939601 ER PT J AU Ferrario, CM Ahmad, S Varagic, J Cheng, CP Groban, L Wang, H Collawn, JF Dell'Italia, LJ AF Ferrario, Carlos M. Ahmad, Sarfaraz Varagic, Jasmina Cheng, Che Ping Groban, Leanne Wang, Hao Collawn, James F. Dell'Italia, Louis J. TI Intracrine angiotensin II functions originate from noncanonical pathways in the human heart SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Review DE angiotensin-(1-12); angiotensin converting enzyme inhibitors; heart chymase; hypertension; heart failure ID MAST-CELL CHYMASE; MOLECULAR-WEIGHT ANGIOTENSINOGEN; CONVERTING ENZYME-INHIBITION; AMINO-ACID-SEQUENCE; BLOOD-PRESSURE; CARDIOVASCULAR EVENTS; INTRACELLULAR RENIN; RECEPTOR BLOCKERS; FORMING PATHWAYS; CARDIAC RENIN AB Although it is well-known that excess renin angiotensin system (RAS) activity contributes to the pathophysiology of cardiac and vascular disease, tissue-based expression of RAS genes has given rise to the possibility that intracellularly produced angiotensin II (Ang II) may be a critical contributor to disease processes. An extended form of angiotensin I (Ang I), the dodecapeptide angiotensin-(1-12) [Ang-(1-12)], that generates Ang II directly from chymase, particularly in the human heart, reinforces the possibility that an alternative noncanonical renin independent pathway for Ang II formation may be important in explaining the mechanisms by which the hormone contributes to adverse cardiac and vascular remodeling. This review summarizes the work that has been done in evaluating the functional significance of Ang-(1-12) and how this substrate generated from angiotensinogen by a yet to be identified enzyme enhances knowledge about Ang II pathological actions. C1 [Ferrario, Carlos M.; Ahmad, Sarfaraz; Varagic, Jasmina] Wake Forest Univ, Hlth Sci Ctr, Dept Surg, Winston Salem, NC 27109 USA. [Ferrario, Carlos M.; Ahmad, Sarfaraz; Varagic, Jasmina] Wake Forest Univ, Hlth Sci Ctr, Dept Internal Med Nephrol, Winston Salem, NC 27109 USA. [Ferrario, Carlos M.; Ahmad, Sarfaraz; Varagic, Jasmina] Wake Forest Univ, Hlth Sci Ctr, Dept Physiol Pharmacol, Winston Salem, NC 27109 USA. [Varagic, Jasmina; Groban, Leanne] Wake Forest Univ, Hypertens & Vasc Res Ctr, Winston Salem, NC 27109 USA. [Cheng, Che Ping] Wake Forest Univ, Hlth Sci Ctr, Dept Internal Med, Sect Cardiovasc Med, Winston Salem, NC 27109 USA. [Groban, Leanne; Wang, Hao] Wake Forest Univ, Hlth Sci Ctr, Dept Anesthesiol, Winston Salem, NC 27109 USA. [Collawn, James F.; Dell'Italia, Louis J.] Univ Alabama Birmingham, Dept Cell Biol, Birmingham, AL 35294 USA. [Collawn, James F.; Dell'Italia, Louis J.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA. [Collawn, James F.; Dell'Italia, Louis J.] Univ Alabama Birmingham, Dept Physiol, Birmingham, AL 35294 USA. [Dell'Italia, Louis J.] Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Dell'Italia, Louis J.] Birmingham Vet Affairs Med Ctr, Dept Vet Affairs, Birmingham, AL USA. RP Ferrario, CM (reprint author), Wake Forest Univ, Hlth Sci Ctr, Winston Salem, NC 27157 USA. EM cferrari@wakehealth.edu FU National Heart, Lung, and Blood Institute of the National Institutes of Health [2P01 HL-051952] FX The studies described here were funded, in part, by Program Project Grant 2P01 HL-051952 from the National Heart, Lung, and Blood Institute of the National Institutes of Health. NR 160 TC 2 Z9 3 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 EI 1522-1539 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD AUG PY 2016 VL 311 IS 2 BP H404 EP H414 DI 10.1152/ajpheart.00219.2016 PG 11 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA DY3DK UT WOS:000384970800010 PM 27233763 ER PT J AU Adler, JT Markmann, JF Yeh, H AF Adler, Joel T. Markmann, James F. Yeh, Heidi TI Renal allograft thrombosis after living donor transplantation: risk factors and obstacles to retransplantation SO CLINICAL TRANSPLANTATION LA English DT Article DE policy; renal transplantation; retransplantation; sensitization; thrombosis ID KIDNEY-TRANSPLANTATION; VASCULAR COMPLICATIONS; SINGLE-CENTER; RECIPIENTS; SURVIVAL AB Introduction: Early allograft thrombosis is a devastating complication that often leads to graft loss after living donor kidney transplantation. In addition to the psychological effects on donor and recipient, it could make future kidney matches challenging due to sensitization. Patients and Methods: The Scientific Registry of Transplant Recipients (SRTR) was queried for adult patients undergoing living donor renal transplantation from 2001 to 2010. Sensitization was defined as a panel reactive antibody of >= 50%. Early allograft thrombosis included events within 30 d of transplantation. Results: In multivariable logistic regression, recipient female gender (odds ratio [OR] 2.24, p < 0.001) and right kidneys (OR 1.46, p < 0.001) were associated with increased risk of thrombosis, while increasing recipient age per 10 yr (OR 0.62, p < 0.001) and recipient Asian race/ethnicity (OR 0.34, p = 0.02) were protective. In a time-varying Cox model examining factors affecting the likelihood of retransplantation, the chance of retransplantation was 37% lower (p = 0.01) once patients became sensitized. The median time to sensitization after transplantation was 288 d. Conclusions: Even with relatively brief exposure to foreign antigen, sensitization occurs and delays retransplantation for recipients of living donor kidneys with early allograft thrombosis. C1 [Adler, Joel T.; Markmann, James F.; Yeh, Heidi] Massachusetts Gen Hosp, Div Transplant Surg, Dept Surg, Boston, MA 02114 USA. [Adler, Joel T.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, 75 Francis St, Boston, MA 02115 USA. RP Yeh, H (reprint author), Massachusetts Gen Hosp, Div Transplant Surg, 55 Fruit St,White 516, Boston, MA 02114 USA. EM hyeh@partners.org OI Adler, Joel/0000-0001-8190-3444 FU Arthur Tracy Cabot fellowship from the Center for Surgery and Public Health at Brigham and Women's Hospital FX JTA is funded by the Arthur Tracy Cabot fellowship from the Center for Surgery and Public Health at Brigham and Women's Hospital. NR 19 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0902-0063 EI 1399-0012 J9 CLIN TRANSPLANT JI Clin. Transplant. PD AUG PY 2016 VL 30 IS 8 BP 864 EP 871 DI 10.1111/ctr.12750 PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA DZ3OI UT WOS:000385757400001 PM 27101358 ER PT J AU Myer, L Phillips, TK Zerbe, A Ronan, A Hsiao, NY Mellins, CA Remien, RH Le Roux, SM Brittain, K Ciaranello, A Petro, G McIntyre, JA Abrams, EJ AF Myer, Landon Phillips, Tamsin K. Zerbe, Allison Ronan, Agnes Hsiao, Nei-Yuan Mellins, Claude A. Remien, Robert H. Le Roux, Stanzi M. Brittain, Kirsty Ciaranello, Andrea Petro, Greg McIntyre, James A. Abrams, Elaine J. TI Optimizing Antiretroviral Therapy (ART) for Maternal and Child Health (MCH): Rationale and Design of the MCH-ART Study SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; antiretroviral therapy; PMTCT; integration; adherence; retention ID SUB-SAHARAN AFRICA; HIV TRANSMISSION; SOUTH-AFRICA; PREVENTION; WOMEN; PREGNANCY; ADHERENCE; IMPLEMENTATION; SERVICES; REGIMENS AB Background: Prevention of mother-to-child transmission of HIV implementation faces significant challenges globally, particularly in the context of universal lifelong antiretroviral therapy (ART) for all HIV-infected pregnant women. Methods: We describe the rationale and methods of the Maternal and Child Health-Antiretroviral Therapy (MCH-ART) study, an implementation science project examining strategies for providing HIV care and treatment to HIV-infected women who initiate ART during pregnancy and their HIV-exposed infants. Results: MCH-ART is composed of 3 interrelated study designs across the antenatal and postnatal periods. Phase 1 is a cross-sectional evaluation of consecutive HIV-infected pregnant women seeking antenatal care; phase 2 is an observational cohort of all women from phase 1 who are eligible for initiation of ART following local guidelines; and phase 3 is a randomized trial of strategies for delivering ART to breastfeeding women from phase 2 during the postpartum period. During each phase, a set of study measurement visits is carried out separately from antenatal care and ART services; a maximum of 9 visits takes place from the beginning of antenatal care through 12 months postpartum. In parallel, in-depth interviews are used to examine issues of ART adherence and retention qualitatively, and costs and cost-effectiveness of models of care are examined. Separate substudies examine health outcomes in HIV-uninfected women and their HIV-unexposed infants, and the role of the adherence club model for long-term adherence and retention. Discussion: Combining observational and experimental components, the MCH-ART study presents a novel approach to understand and optimize ART delivery for MCH. C1 [Myer, Landon; Phillips, Tamsin K.; Le Roux, Stanzi M.; Brittain, Kirsty; McIntyre, James A.] Univ Cape Town, Sch Publ Hlth & Family Med, Div Epidemiol & Biostat, Anzio Rd, ZA-7925 Cape Town, South Africa. [Myer, Landon; Phillips, Tamsin K.; Ronan, Agnes; Brittain, Kirsty] Univ Cape Town, Sch Publ Hlth & Family Med, Ctr Infect Dis Epidemiol & Res, Cape Town, South Africa. [Zerbe, Allison; Abrams, Elaine J.] Columbia Univ, Mailman Sch Publ Hlth, ICAP, New York, NY USA. [Hsiao, Nei-Yuan] Univ Cape Town, Groote Schuur Hosp, Natl Hlth Lab Serv, Cape Town, South Africa. [Hsiao, Nei-Yuan] Univ Cape Town, Div Med Virol, Cape Town, South Africa. [Mellins, Claude A.; Remien, Robert H.] New York State Psychiat Inst & Hosp, HIV Ctr Clin & Behav Studies, New York, NY 10032 USA. [Mellins, Claude A.; Remien, Robert H.] Columbia Univ, New York, NY USA. [Ciaranello, Andrea] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Petro, Greg] Univ Cape Town, New Somerset Hosp, Dept Obstet & Gynaecol, Cape Town, South Africa. [McIntyre, James A.] Anova Hlth Inst, Johannesburg, South Africa. [Abrams, Elaine J.] Columbia Univ, Coll Phys & Surg, New York, NY USA. RP Myer, L (reprint author), Univ Cape Town, Sch Publ Hlth & Family Med, Div Epidemiol & Biostat, Anzio Rd, ZA-7925 Cape Town, South Africa. EM landon.myer@uct.ac.za FU President's Emergency Plan for AIDS Relief through National Institute of Child Health and Human Development [1R01HD074558]; Elizabeth Glaser Pediatric AIDS Foundation; South African Medical Research Council; Fogarty Foundation (NIH Fogarty International Center) [5R25TW009340]; Office of AIDS Research FX Supported by the President's Emergency Plan for AIDS Relief through the National Institute of Child Health and Human Development, Grant 1R01HD074558. Additional funding comes from the Elizabeth Glaser Pediatric AIDS Foundation, the South African Medical Research Council, the Fogarty Foundation (NIH Fogarty International Center Grant #5R25TW009340), and the Office of AIDS Research. NR 26 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD AUG 1 PY 2016 VL 72 SU 2 BP S189 EP S196 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA DY6YG UT WOS:000385275100014 PM 27355508 ER PT J AU Takx, RAP Ishai, A Truong, QA MacNabb, MH Scherrer-Crosbie, M Tawakol, A AF Takx, Richard A. P. Ishai, Amorina Truong, Quynh A. MacNabb, Meghan H. Scherrer-Crosbie, Marielle Tawakol, Ahmed TI Supraclavicular Brown Adipose Tissue F-18-FDG Uptake and Cardiovascular Disease SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE brown adipose tissue; positron-emission tomography; arterial FDG uptake; cardiovascular disease ID INSULIN-RESISTANCE; ADULT HUMANS; INFLAMMATION; RISK; FLUORODEOXYGLUCOSE; EVENTS; FAT; ATHEROSCLEROSIS; TOMOGRAPHY; PET/CT AB Preclinical data suggest a negative correlation between brown adipose tissue (BAT) and the degree of coronary atherosclerosis. We sought to evaluate the relationship between F-18-FDG uptake in supraclavicular BAT in relation to arterial inflammation and subsequent cardiovascular disease (CVD) events in humans. Methods: Individuals who underwent F-18-FDG PET/CT for clinical indications but who did not have either cancer or known atherosclerotic disease at the time of imaging were included. A radiologist masked to clinical data measured F-18-FDG uptake within BAT (in the supraclavicular region) as well as in subcutaneous adipose tissues. Tissue density was evaluated using CT (Hounsfield units). Arterial inflammation was assessed by measuring arterial F-18-FDG uptake and calculating target-to-background ratio. CVD events were independently adjudicated by masked cardiologists. Thereafter, the relationship between BAT activity and CVD events was evaluated. Results: A total of 443 patients (age, 55 y [44-66 y]; 44% men; body mass index [BMI], 26 [range, 23-31]) were included, and 30 patients experienced a cardiovascular event during a median follow-up of 4 y. BAT activity negatively correlated with arterial inflammation (r = -0.178, P < 0.01), a relationship that persisted after correcting for age and BMI (r = -0.147, P < 0.01). When either high sensitivity or high accuracy thresholds (from receiver-operating curve analyses) were used to define elevated BAT, high BAT was associated with a reduced risk of CVD events (P = 0.048), even after correcting for age (P = 0.037). Conclusion: Our results suggest that increased supraclavicular BAT activity is inversely associated with arterial inflammation, independently of age and BMI. Additionally, increased BAT may be associated with fewer cardiovascular events. C1 [Takx, Richard A. P.; Ishai, Amorina; MacNabb, Meghan H.; Tawakol, Ahmed] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Takx, Richard A. P.; Ishai, Amorina; MacNabb, Meghan H.; Scherrer-Crosbie, Marielle; Tawakol, Ahmed] Harvard Med Sch, Boston, MA USA. [Takx, Richard A. P.] Univ Med Ctr Utrecht, Dept Radiol, Utrecht, Netherlands. [Truong, Quynh A.] Weill Cornell Coll Med, Dept Radiol, New York, NY USA. [Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Tawakol, A (reprint author), Massachusetts Gen Hosp, 165 Cambridge St,Ste 400, Boston, MA 02114 USA. EM atawakol@partners.org NR 29 TC 2 Z9 2 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD AUG 1 PY 2016 VL 57 IS 8 BP 1221 EP 1225 DI 10.2967/jnumed.115.166025 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DY6UJ UT WOS:000385263600017 PM 26795284 ER PT J AU Sonis, ST Mendes, RA AF Sonis, Stephen T. Mendes, Rui Amaral TI Could the PI3K canonical pathway be a common link between chronic inflammatory conditions and oral carcinogenesis? SO JOURNAL OF ORAL PATHOLOGY & MEDICINE LA English DT Review DE candidiasis; graft-vs.-host disease; inflammation; lichen planus; oral carcinogenesis; PI3K signaling pathways ID SQUAMOUS-CELL CARCINOMA; VERSUS-HOST-DISEASE; CANDIDA-ALBICANS; CANCER; HEAD; TRANSPLANTATION; INTERLEUKIN-6; ACTIVATION; SURVIVAL; TARGETS AB The association between chronic inflammatory disorders and oral carcinogenesis has been both a source of interest and contention. Based upon its central importance in oral carcinogenesis, the finding that the PI3k/Akt/mTOR pathway is activated in oral lichen planus, chronic graftversus-host disease, and chronic oral candidiasis suggests that it may provide a link between benign and malignant oral conditions. Here, we discuss a possible mechanistic rationale that addresses the activation of this important signaling pathway and its downstream events, while correlating it with the carcinogenic potential of chronic oral disorders. C1 [Sonis, Stephen T.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Sonis, Stephen T.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sonis, Stephen T.] Biomodels LLC, Boston, MA USA. [Mendes, Rui Amaral] Case Western Reserve Univ, Sch Dent Med, Dept Oral & Maxillofacial Med & Diagnost Sci, Oral & Maxillofacial Med, Cleveland, OH 44106 USA. RP Sonis, ST (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM ssonis@partners.org OI Amaral Mendes, Rui/0000-0001-7628-8598 NR 42 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0904-2512 EI 1600-0714 J9 J ORAL PATHOL MED JI J. Oral Pathol. Med. PD AUG PY 2016 VL 45 IS 7 BP 469 EP 474 DI 10.1111/jop.12436 PG 6 WC Dentistry, Oral Surgery & Medicine; Pathology SC Dentistry, Oral Surgery & Medicine; Pathology GA DZ2ZL UT WOS:000385711900001 PM 26991523 ER PT J AU Karp, JF DiNapoli, EA Wetherell, J Bolon, C Rodriguez, E Shega, J Weiner, DK AF Karp, Jordan F. DiNapoli, Elizabeth A. Wetherell, Julie Bolon, Chloe Rodriguez, Eric Shega, Joseph 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 IX: Anxiety SO PAIN MEDICINE LA English DT Article DE Anxiety; Low Back Pain; Chronic Pain; Avoidance Behavior; Cognitive Behavior Therapy; Fear ID COGNITIVE-BEHAVIORAL THERAPY; PRIMARY-CARE PATIENTS; CHRONIC MUSCULOSKELETAL PAIN; LATE-LIFE ANXIETY; PSYCHIATRIC-DISORDERS; MENTAL-DISORDERS; CONTROLLED-TRIAL; METAANALYSIS; PREVALENCE; DEPRESSION AB Objective. As a part of a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults, this article focuses on anxiety-a significant contributor of reduced health-related quality of life, increased use of medical services, and heightened disability in older adults with CLBP. Methods. A modified Delphi technique was used to develop an algorithm for the screening and clinical care of older adults with CLBP and anxiety. A 4-member content expert panel and a nine-member primary care panel were involved in this iterative development process. Evidence underlying the recommendations is not strictly based on VA populations; therefore, the algorithm can be applied in both VHA and civilian settings. The illustrative clinical case was taken from one of the contributor's clinical practice. Results. We present a treatment algorithm and supporting tables to be used by providers treating older adults who have anxiety and CLBP. A case of an older adult with anxiety and CLBP is provided to illustrate the approach to management. Conclusions. To promote early engagement in evidence-based treatments, providers should routinely evaluate anxiety in older adults with CLBP using a screening and treatment algorithm. C1 [Karp, Jordan F.; Weiner, Debra K.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Karp, Jordan F.; DiNapoli, Elizabeth A.; Bolon, Chloe; 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. [DiNapoli, Elizabeth A.] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA. [Wetherell, Julie] VA San Diego Healthcare Syst, San Diego, CA USA. [Wetherell, Julie] Univ Calif San Diego, San Diego, CA 92103 USA. [Rodriguez, Eric; Weiner, Debra K.] Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA USA. [Shega, Joseph] VITAS Healthcare, Miami, FL USA. RP Weiner, DK (reprint author), 3471 Fifth Ave,Suite 500, Pittsburgh, PA 15213 USA. EM Debra.Weiner@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development Service FX This material is based on work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development Service. NR 57 TC 1 Z9 1 U1 9 U2 9 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 AUG PY 2016 VL 17 IS 8 BP 1423 EP 1435 DI 10.1093/pm/pnw135 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA DZ1WQ UT WOS:000385632800006 PM 27346887 ER PT J AU Park, EM Deal, AM Check, DK Hanson, LC Reeder-Hayes, KE Mayer, DK Yopp, JM Song, MK Muriel, AC Rosenstein, DL AF Park, Eliza M. Deal, Allison M. Check, Devon K. Hanson, Laura C. Reeder-Hayes, Katherine E. Mayer, Deborah K. Yopp, Justin M. Song, Mi-Kyung Muriel, Anna C. Rosenstein, Donald L. TI Parenting concerns, quality of life, and psychological distress in patients with advanced cancer SO PSYCHO-ONCOLOGY LA English DT Article ID SOCIAL SUPPORT SURVEY; BREAST-CANCER; INCURABLE CANCER; CHILDREN; EXPERIENCES; DEPRESSION; PROGRAM; QUESTIONNAIRE; INTERVENTION; PREVALENCE AB Objective: Parents with life-limiting illness anticipate the loss of their parental role and the long-term consequences of their illness on their children. The purpose of this study was to examine relationships between parenting concerns, quality of life (QOL), and symptoms of depression and anxiety in parents with advanced cancer who have dependent children. Methods: Sixty-three parents diagnosed with a Stage IV solid malignancy completed the Hospital Anxiety Depression Scale (HADS), Parenting Concerns Questionnaire (PCQ), and Functional Assessment of Cancer Therapy General (FACT-C). The Medical Outcomes Study Social Support Survey (social support) and Eastern Cooperative Oncology Group (ECOG) performance status were assessed as potential covariates. We performed descriptive statistics and multivariable linear regression models for depression, anxiety, and QOL measures. Results: Mean PCQ score was 2.3 (SD 0.9), reflecting mild to moderate parenting concerns. Average depression and anxiety scores were 6.0 (SD 4.2) and 8.2 (SD 3.9), respectively. PCQ scores were associated with depressive symptoms (r = 0.46, p < 0.001), anxiety symptoms (r =0.52, p < 0.0001), and QOL scores (r= 0.60, p <0.001). The relationship of PCQ scores to anxiety symptoms (B=1.5 p = 0.016) and QOL (B= 5.7, p =0.02) remained significant after controlling for ECOG status, social support, and treatment status. Conclusions: Parenting concerns are associated with anxiety and depressive symptoms and worse QOL in parents diagnosed with advanced cancer. Further studies that evaluate how parental status affects coping and psychological distress in advanced cancer are needed. Copyright (C) 2015 John Wiley & Sons, Ltd. C1 [Park, Eliza M.; Yopp, Justin M.; Rosenstein, Donald L.] Univ N Carolina, Dept Psychiat, 170 Manning Dr,Campus Box 7305, Chapel Hill, NC 27599 USA. [Deal, Allison M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. [Check, Devon K.] Univ N Carolina, Dept Hlth Policy & Management, Chapel Hill, NC USA. [Hanson, Laura C.] Univ N Carolina, Dept Med, Div Geriatr Med, Chapel Hill, NC USA. [Hanson, Laura C.] Univ N Carolina, Dept Med, Palliat Care Program, Chapel Hill, NC USA. [Reeder-Hayes, Katherine E.; Rosenstein, Donald L.] Univ N Carolina, Dept Med, Div Hematol & Oncol, Chapel Hill, NC USA. [Mayer, Deborah K.; Song, Mi-Kyung] Univ N Carolina, Sch Nursing, Chapel Hill, NC USA. [Muriel, Anna C.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. RP Park, EM (reprint author), Univ N Carolina, Dept Psychiat, 170 Manning Dr,Campus Box 7305, Chapel Hill, NC 27599 USA. EM leeza_park@med.unc.edu FU North Carolina University Cancer Research Fund; National Center for Advancing Translational Sciences (NCATS), National Institutes of Health [1UL1TR001111] FX The project described was supported by the North Carolina University Cancer Research Fund and the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, through Grant Award Number 1UL1TR001111. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 26 TC 2 Z9 2 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD AUG PY 2016 VL 25 IS 8 BP 942 EP 948 DI 10.1002/pon.3935 PG 7 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA DZ3CO UT WOS:000385721800009 PM 26282575 ER PT J AU Ackman, JB Gaissert, HA Lanuti, M Digumarthy, SR Shepard, JAO Halpern, EF Wright, CD AF Ackman, Jeanne B. Gaissert, Henning A. Lanuti, Michael Digumarthy, Subba R. Shepard, Jo-Anne O. Halpern, Elkan F. Wright, Cameron D. TI Impact of Nonvascular Thoracic MR Imaging on the Clinical Decision Making of Thoracic Surgeons: A 2-year Prospective Study SO RADIOLOGY LA English DT Article ID SOLITARY PULMONARY NODULES; SIGNAL INTENSITY; CYSTIC-FIBROSIS; POTENTIAL ROLE; CT; DIAGNOSIS; DISEASE; MASSES; DIFFERENTIATION; MEDIASTINUM AB Purpose: To determine the impact of nonvascular thoracic magnetic resonance (MR) imaging on the clinical decision making and diagnostic certainty of thoracic surgeons. Materials and Methods: Seven thoracic surgeons at Massachusetts General Hospital, an academic quaternary referral hospital, participated in this 2-year, prospective, institution review board-approved, HIPAA-compliant pre-and post-MR imaging survey study after completing a one-time demographic survey. Between July 16, 2013, and July 13, 2015, each time a thoracic surgeon ordered a nonvascular thoracic MR imaging study via radiology order entry, he or she was sent a link to the pre-test survey that ascertained the clinical rationale for MR imaging, the clinical management plan if MR imaging was not an option, and pre-test diagnostic certainty. Upon completion of the MR imaging report, the surgeon was sent a link to the post-test survey assessing if/how MR imaging changed clinical management, the surgeon's comfort with the clinical management plan, and post-test diagnostic certainty. Data were analyzed with Student t, Wilcoxon, and McNemar tests. Results: A total of 99 pre-and post-test surveys were completed. Most MR imaging studies (64 of 99 [65%]) were requested because of indeterminate computed tomographic findings. The use of MR imaging significantly reduced the number of planned surgical interventions (P < .001), modified the surgical approach in 54% (14 of 26) of surgical cases, and increased surgeon comfort with the patient management plan in 95% (94 of 99) of cases. Increased diagnostic certainty as a result of MR imaging was highly significant (P < .0001). In 21% (21 of 99) of cases, definitive MR imaging results warranted no further follow-up or clinical care. Conclusion: In appropriate cases, assessment with nonvascular thoracic MR imaging substantially affects the clinical decision making and diagnostic certainty of thoracic surgeons. C1 [Ackman, Jeanne B.; Digumarthy, Subba R.; Shepard, Jo-Anne O.] Harvard Med Sch, Massachusetts Gen Hosp, Div Thorac Imaging & Intervent, Dept Radiol, 55 Fruit St,Founders House 202, Boston, MA 02114 USA. [Gaissert, Henning A.; Lanuti, Michael; Wright, Cameron D.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,Founders House 202, Boston, MA 02114 USA. [Halpern, Elkan F.] Harvard Med Sch, Massachusetts Gen Hosp, Inst Technol Assessment, 55 Fruit St,Founders House 202, Boston, MA 02114 USA. RP Ackman, JB (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Div Thorac Imaging & Intervent, Dept Radiol, 55 Fruit St,Founders House 202, Boston, MA 02114 USA. EM jackman@mgh.harvard.edu FU Cambridge Healthtech FX J.B.A. disclosed no relevant relationships. H.A.G. disclosed no relevant relationships. M.L. disclosed no relevant relationships. S.R.D. disclosed no relevant relationships. J.A.O.S. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: provided expert testimony for CRICO. Other relationships: disclosed no relevant relationships. E.F.H. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: consultant for Hologic, Gamma Medica, and Real Imaging; payment for lectures from Cambridge Healthtech; and travel/accommodation/meeting expenses from RSNA. Other relationships: disclosed no relevant relationships. C.D.W. disclosed no relevant relationships. NR 36 TC 2 Z9 2 U1 1 U2 1 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 AUG PY 2016 VL 280 IS 2 BP 464 EP 474 DI 10.1148/radiol.2016152004 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DY6UW UT WOS:000385265200014 PM 26909650 ER PT J AU Ahmadi, E Katnani, HA Besheli, LD Gu, Q Atefi, R Villeneuve, MY Eskandar, E Lev, MH Golby, AJ Gupta, R Bonmassar, G AF Ahmadi, Emad Katnani, Husam A. Besheli, Laleh Daftari Gu, Qiang Atefi, Reza Villeneuve, Martin Y. Eskandar, Emad Lev, Michael H. Golby, Alexandra J. Gupta, Rajiv Bonmassar, Giorgio TI An Electrocorticography Grid with Conductive Nanoparticles in a Polymer Thick Film on an Organic Substrate Improves CT and MR Imaging SO RADIOLOGY LA English DT Article ID EPILEPSY; ARRAYS; STATE AB Purpose: To develop an electrocorticography (ECoG) grid by using deposition of conductive nanoparticles in a polymer thick film on an organic substrate (PTFOS) that induces minimal, if any, artifacts on computed tomographic (CT) and magnetic resonance (MR) images and is safe in terms of tissue reactivity and MR heating. Materials and Methods: All procedures were approved by the Animal Care and Use Committee and complied with the Public Health Services Guide for the Care and Use of Animals. Electrical functioning of PTFOS for cortical recording and stimulation was tested in two mice. PTFOS disks were implanted in two mice; after 30 days, the tissues surrounding the implants were harvested, and tissue injury was studied by using immunostaining. Five neurosurgeons rated mechanical properties of PTFOS compared with conventional grids by using a three-level Likert scale. Temperature increases during 30 minutes of 3-T MR imaging were measured in a head phantom with no grid, a conventional grid, and a PTFOS grid. Two neuroradiologists rated artifacts on CT and MR images of a cadaveric head specimen with no grid, a conventional grid, and a PTFOS grid by using a four-level Likert scale, and the mean ratings were compared between grids. Results: Oscillatory local field potentials were captured with cortical recordings. Cortical stimulations in motor cortex elicited muscle contractions. PTFOS implants caused no adverse tissue reaction. Mechanical properties were rated superior to conventional grids (x(2) test, P<.05). The temperature increase during MR imaging for the three cases of no grid, PTFOS grid, and conventional grid was 3.84 degrees C, 4.05 degrees C, and 10.13 degrees C, respectively. PTFOS induced no appreciable artifacts on CT and MR images, and PTFOS image quality was rated significantly higher than that with conventional grids (two-tailed t test, P<.05). Conclusion: PTFOS grids may be an attractive alternative to conventional ECoG grids with regard to mechanical properties, 3-T MR heating profile, and CT and MR imaging artifacts. (C) RSNA, 2016 C1 [Ahmadi, Emad; Atefi, Reza; Villeneuve, Martin Y.; Bonmassar, Giorgio] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, 75 Third Ave,Room 1-402, Charlestown, MA 02129 USA. [Ahmadi, Emad; Besheli, Laleh Daftari; Lev, Michael H.; Gupta, Rajiv] Harvard Med Sch, Massachusetts Gen Hosp, Adv X Ray Imaging Sci Ctr, Dept Radiol, Boston, MA USA. [Katnani, Husam A.; Eskandar, Emad] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA USA. [Gu, Qiang] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Golby, Alexandra J.] Harvard Med Sch, Brigham & Womens Hosp, Dept Neurosurg, Boston, MA USA. RP Bonmassar, G (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, 75 Third Ave,Room 1-402, Charlestown, MA 02129 USA. EM giorgio@nmr.mgh.harvard.edu FU National Institutes of Health [5R43NS071988-02, U01-NS075026, 1R21EB016449-01A1]; National Center for Research Resources [P41-RR14075]; National Center for Image Guided Therapy [P41EB015898]; MIND Institute FX Supported by the National Center for Research Resources (grant P41-RR14075), National Center for Image Guided Therapy (grant P41EB015898), and the MIND Institute.; This research was supported by the National Institutes of Health (grants 5R43NS071988-02, U01-NS075026, and 1R21EB016449-01A1) NR 20 TC 0 Z9 0 U1 2 U2 2 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 AUG PY 2016 VL 280 IS 2 BP 595 EP 601 DI 10.1148/radiol.2016142529 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DY6UW UT WOS:000385265200028 PM 26844363 ER PT J AU Karras, E Lu, NJ Zuo, GX Tu, XM Stephens, B Draper, J Thompson, C Bossarte, RM AF Karras, Elizabeth Lu, Naiji Zuo, Guoxin Tu, Xin M. Stephens, Brady Draper, John Thompson, Caitlin Bossarte, Robert M. TI Measuring Associations of the Department of Veterans Affairs' Suicide Prevention Campaign on the Use of Crisis Support Services SO SUICIDE AND LIFE-THREATENING BEHAVIOR LA English DT Article ID MASS-MEDIA CAMPAIGNS; HEALTH BEHAVIOR; CALLS AB Campaigns have become popular in public health approaches to suicide prevention; however, limited empirical investigation of their impact on behavior has been conducted. To address this gap, utilization patterns of crisis support services associated with the Department of Veterans Affairs' Veterans Crisis Line (VCL) suicide prevention campaign were examined. Daily call data for the National Suicide Prevention Lifeline, VCL, and 1-800-SUICIDE were modeled using a novel semi-varying coefficient method. Analyses reveal significant increases in call volume to both targeted and broad resources during the campaign. Findings underscore the need for further research to refine measurement of the effects of these suicide prevention efforts. C1 [Karras, Elizabeth; Tu, Xin M.; Stephens, Brady] US Dept Vet Affairs, VISN Ctr Excellence Suicide Prevent 2, 400 Ft Hill Ave, Canandaigua, NY 14424 USA. [Karras, Elizabeth; Tu, Xin M.] Univ Rochester, Dept Psychiat, Rochester, NY USA. [Lu, Naiji; Tu, Xin M.] Univ Rochester, Dept Biostat & Computat Biol, Rochester, NY USA. [Zuo, Guoxin] Cent China Normal Univ, Sch Math & Stat, Wuhan, Peoples R China. [Draper, John] Link2Hlth Solut Inc, Natl Suicide Prevent Lifeline, New York, NY USA. [Thompson, Caitlin] US Dept Vet Affairs, Mental Hlth Serv, Suicide Prevent & Community Engagement Program, Washington, DC USA. [Bossarte, Robert M.] US Dept Vet Affairs, Program Epidemiol, Postdeployment Hlth Off Publ Hlth, Washington, DC USA. [Bossarte, Robert M.] Harvard Univ, Dept Epidemiol, Cambridge, MA 02138 USA. RP Karras, E (reprint author), US Dept Vet Affairs, VISN Ctr Excellence Suicide Prevent 2, 400 Ft Hill Ave, Canandaigua, NY 14424 USA. EM Elizabeth.Karras@va.gov NR 22 TC 1 Z9 1 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0363-0234 EI 1943-278X J9 SUICIDE LIFE-THREAT JI Suicide Life-Threat. Behav. PD AUG PY 2016 VL 46 IS 4 BP 447 EP 456 DI 10.1111/sltb.12231 PG 10 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DZ2XM UT WOS:000385706100005 PM 26880716 ER PT J AU Virani, SS AF Virani, Salim S. TI The 2013 ACC/AHA Cholesterol Management Guideline: Clearing the Confusion from Noncontroversial Components SO TEXAS HEART INSTITUTE JOURNAL LA English DT Editorial Material DE Cholesterol LDL/blood; coronary artery disease/prevention & control; guideline implementation; hypercholesterolemia/drug therapy; provider behavior; risk assessment; societies, medical; statins C1 [Virani, Salim S.] Hlth Serv Res & Dev Ctr Innovat, Michael E DeBakey Vet Affairs Med Ctr, Hlth Policy Qual & Informat Program, Houston, TX 77030 USA. [Virani, Salim S.] Baylor Coll Med, Dept Med, Sect Cardiovasc Res, Houston, TX 77030 USA. [Virani, Salim S.] Methodist DeBakey Heart & Vasc Ctr, Ctr Cardiovasc Dis Prevent, Houston, TX 77030 USA. RP Virani, SS (reprint author), Michael E DeBakey VA Med Ctr, Hlth Serv Res & Dev 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM virani@bcm.edu OI Virani, Salim/0000-0001-9541-6954 NR 6 TC 0 Z9 0 U1 0 U2 0 PU TEXAS HEART INST PI HOUSTON PA PO BOX 20345, HOUSTON, TX 77225-0345 USA SN 1526-6702 J9 TEX HEART I J JI Tex. Heart Inst. J. PD AUG PY 2016 VL 43 IS 4 BP 313 EP 314 DI 10.14503/THIJ-16-5798 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DZ5RH UT WOS:000385918700010 PM 27547139 ER PT J AU Kasinath, BS AF Kasinath, Balakuntalam S. TI The podocyte and the proteoglycan SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Editorial Material ID GLOMERULAR-BASEMENT-MEMBRANE; HEPARAN-SULFATE; PROTEINURIA C1 [Kasinath, Balakuntalam S.] Univ Texas San Antonio, Hlth Sci Ctr, South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Kasinath, BS (reprint author), Univ Texas San Antonio, Hlth Sci Ctr, Dept Med, MC7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM kasinath@uthscsa.edu NR 9 TC 0 Z9 0 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD AUG 1 PY 2016 VL 311 IS 2 BP F310 EP F311 DI 10.1152/ajprenal.00295.2016 PG 2 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA DY3FP UT WOS:000384976500008 PM 27226109 ER PT J AU Uchendu, US Omalu, BI Cifu, DX Egede, LE AF Uchendu, Uchenna S. Omalu, Bennet I. Cifu, David X. Egede, Leonard E. TI Repeated Concussions: Time to Spur Action Among Vulnerable Veterans SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID TRAUMATIC BRAIN-INJURY; ENCEPHALOPATHY C1 [Uchendu, Uchenna S.] US Dept Vet Affairs, Washington, DC USA. [Omalu, Bennet I.] Univ Calif Davis, Dept Pathol, Davis, CA 95616 USA. [Cifu, David X.] Virginia Commonwealth Univ, Sch Med, Richmond, VA 23284 USA. [Cifu, David X.] US Dept Vet Affairs, Richmond, VA USA. [Egede, Leonard E.] Med Univ South Carolina, Charleston, SC USA. [Egede, Leonard E.] US Dept Vet Affairs, Charleston, SC USA. RP Uchendu, US (reprint author), US Dept Vet Affairs, Off Hlth Equ, 810 Vermont Ave NW, Washington, DC 20420 USA. EM Uchenna.Uchendu2@va.gov NR 7 TC 0 Z9 0 U1 2 U2 2 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 AUG PY 2016 VL 106 IS 8 BP 1366 EP 1368 DI 10.2105/AJPH.2016.303293 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DY3HK UT WOS:000384981200024 PM 27310350 ER PT J AU Diaz-Gil, D Haerter, F Falcinelli, S Ganapati, S Hettiarachchi, GK Simons, JCP Zhang, B Grabitz, SD Duarte, IM Cotten, JF Eikermann-Haerter, K Deng, H Chamberlin, NL Isaacs, L Briken, V Eikermann, M AF Diaz-Gil, Daniel Haerter, Friederike Falcinelli, Shane Ganapati, Shweta Hettiarachchi, Gaya K. Simons, Jeroen C. P. Zhang, Ben Grabitz, Stephanie D. Duarte, Ingrid Moreno Cotten, Joseph F. Eikermann-Haerter, Katharina Deng, Hao Chamberlin, Nancy L. Isaacs, Lyle Briken, Volker Eikermann, Matthias TI A Novel Strategy to Reverse General Anesthesia by Scavenging with the Acyclic Cucurbit[n]uril-type Molecular Container Calabadion 2 SO ANESTHESIOLOGY LA English DT Article ID NEUROMUSCULAR-BLOCKING-AGENTS; BURST SUPPRESSION; BRAIN-INJURY; KETAMINE; ETOMIDATE; RATS; EMERGENCE; PROPOFOL; MODEL; SLEEP AB Background: Calabadion 2 is a new drug-encapsulating agent. In this study, the authors aim to assess its utility as an agent to reverse general anesthesia with etomidate and ketamine and facilitate recovery. Methods: To evaluate the effect of calabadion 2 on anesthesia recovery, the authors studied the response of rats to calabadion 2 after continuous and bolus intravenous etomidate or ketamine and bolus intramuscular ketamine administration. The authors measured electroencephalographic predictors of depth of anesthesia (burst suppression ratio and total electroencephalographic power), functional mobility impairment, blood pressure, and toxicity. Results: Calabadion 2 dose-dependently reverses the effects of ketamine and etomidate on electroencephalographic predictors of depth of anesthesia, as well as drug-induced hypotension, and shortens the time to recovery of righting reflex and functional mobility. Calabadion 2 displayed low cytotoxicity in MTS-3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium-based cell viability and adenylate kinase release cell necrosis assays, did not inhibit the human ether-a-go-go-related channel, and was not mutagenic (Ames test). On the basis of maximum tolerable dose and acceleration of righting reflex recovery, the authors calculated the therapeutic index of calabadion 2 in recovery as 16: 1 (95% CI, 10 to 26: 1) for the reversal of ketamine and 3: 1 (95% CI, 2 to 5: 1) for the reversal of etomidate. Conclusions: Calabadion 2 reverses etomidate and ketamine anesthesia in rats by chemical encapsulation at nontoxic concentrations. C1 [Diaz-Gil, Daniel; Haerter, Friederike; Simons, Jeroen C. P.; Grabitz, Stephanie D.; Duarte, Ingrid Moreno; Cotten, Joseph F.; Eikermann, Matthias] Harvard Med Sch, Massachusetts Gen Hosp, Anesthesia Crit Care & Pain Med, Boston, MA USA. [Eikermann-Haerter, Katharina] Harvard Med Sch, Massachusetts Gen Hosp, Radiol, Boston, MA USA. [Deng, Hao] Harvard Med Sch, Massachusetts Gen Hosp, Biostat, Boston, MA USA. [Falcinelli, Shane; Hettiarachchi, Gaya K.; Briken, Volker] Univ Maryland, Cell Biol & Mol Genet, College Pk, MD 20742 USA. [Zhang, Ben; Grabitz, Stephanie D.; Isaacs, Lyle] Univ Maryland, Chem & Biochem, College Pk, MD 20742 USA. [Chamberlin, Nancy L.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Neurol, Boston, MA USA. [Eikermann, Matthias] Univ Duisburg Essen, Univ Hosp Essen, Anesthesia & Crit Care Med, Essen, Germany. RP Eikermann, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM meikermann@partners.org RI Isaacs, Lyle/B-4472-2009; OI Isaacs, Lyle/0000-0002-4079-332X; Briken, Volker/0000-0001-5830-6107 FU Department of Anesthesia, Critical Care and Pain Medicine at Massachusetts General Hospital, Boston, Massachusetts; State of Maryland Technology Development Corporation (TEDCO), Columbia, Maryland; National Institutes of Health, Bethesda, Maryland [R01 HL117871, R01 CA168365]; Howard Hughes Medical Institute (Chevy Chase, Maryland) FX Supported by the Department of Anesthesia, Critical Care and Pain Medicine at Massachusetts General Hospital, Boston, Massachusetts; the State of Maryland Technology Development Corporation (TEDCO), Columbia, Maryland; the National Institutes of Health, Bethesda, Maryland (R01 HL117871 and R01 CA168365); and a grant to the University of Maryland from the Howard Hughes Medical Institute (Chevy Chase, Maryland) Undergraduate Science Education Program. NR 46 TC 1 Z9 1 U1 3 U2 3 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 AUG PY 2016 VL 125 IS 2 BP 333 EP 345 DI 10.1097/ALN.0000000000001199 PG 13 WC Anesthesiology SC Anesthesiology GA DY3VC UT WOS:000385022200013 PM 27341276 ER PT J AU Nanji, KC Bates, DW AF Nanji, Karen C. Bates, David W. TI Counting Errors: Medication or Medical? Reply SO ANESTHESIOLOGY LA English DT Letter ID ADVERSE DRUG EVENTS; HEALTH-CARE PERSONNEL; INTENSIVE-CARE; HOSPITALIZED-PATIENTS; ADMINISTRATION ERROR; AMBULATORY-CARE; ANESTHESIA; FACILITIES; DIVERSION; FREQUENCY C1 [Nanji, Karen C.; Bates, David W.] Massachusetts Gen Hosp, Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Nanji, KC (reprint author), Massachusetts Gen Hosp, Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM knanji@partners.org FU NIGMS NIH HHS [T32 GM007592] NR 44 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 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD AUG PY 2016 VL 125 IS 2 BP 432 EP 437 DI 10.1097/ALN.0000000000001188 PG 7 WC Anesthesiology SC Anesthesiology GA DY3VC UT WOS:000385022200041 PM 27433765 ER PT J AU Ladha, KS Bateman, BT AF Ladha, Karim S. Bateman, Brian T. TI Epidurals and Chronic Postsurgical Pain: Is It Lack of Evidence or Poor Design? Reply SO ANESTHESIOLOGY LA English DT Letter C1 [Ladha, Karim S.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Toronto Gen Hosp, Toronto, ON, Canada. Univ Toronto, Toronto, ON, Canada. RP Ladha, KS (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM karim.ladha@post.harvard.edu FU NICHD NIH HHS [K08 HD075831] NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD AUG PY 2016 VL 125 IS 2 BP 440 EP 441 DI 10.1097/ALN.0000000000001192 PG 3 WC Anesthesiology SC Anesthesiology GA DY3VC UT WOS:000385022200045 PM 27433769 ER PT J AU Kopterides, P Mayr, FB Yende, S AF Kopterides, Petros Mayr, Florian B. Yende, Sachin TI Understanding the sepsis mortality belt: time to buckle down! SO ANNALS OF TRANSLATIONAL MEDICINE LA English DT Editorial Material ID UNITED-STATES C1 [Kopterides, Petros; Mayr, Florian B.; Yende, Sachin] Univ Pittsburgh, Dept Crit Care Med, CRISMA Ctr, Pittsburgh, PA USA. [Mayr, Florian B.; Yende, Sachin] Vet Affairs Pittsburgh Healthcare Syst, Univ Dr Campus,Room 2A128, Pittsburgh, PA 15240 USA. RP Mayr, FB (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Univ Dr Campus,Room 2A128, Pittsburgh, PA 15240 USA. EM florian.mayr@va.gov NR 10 TC 0 Z9 0 U1 0 U2 0 PU AME PUBL CO PI SHEUNG WAN PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG 00000, PEOPLES R CHINA SN 2305-5839 EI 2305-5847 J9 ANN TRANSL MED JI ANN. TRANSL. MED. PD AUG PY 2016 VL 4 IS 16 AR 319 DI 10.21037/atm.2016.08.01 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DY0NM UT WOS:000384793500021 PM 27668239 ER PT J AU Mc Causland, FR Asafu-Adjei, J Betensky, RA Palevsky, PM Waikar, SS AF Mc Causland, Finnian R. Asafu-Adjei, Josephine Betensky, Rebecca A. Palevsky, Paul M. Waikar, Sushrut S. TI Comparison of Urine Output among Patients Treated with More Intensive Versus Less Intensive RRT: Results from the Acute Renal Failure Trial Network Study SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE KIDNEY INJURY; CRITICALLY-ILL PATIENTS; CONTINUOUS VENOVENOUS HEMOFILTRATION; REPLACEMENT THERAPY; HEMODIALYSIS; RECOVERY; SURVIVAL; MULTICENTER; PROGNOSIS; OUTCOMES AB Background and objectives Intensive RRT may have adverse effects that account for the absence of benefit observed in randomized trials of more intensive versus less intensive RRT. We wished to determine the association of more intensive RRT with changes in urine output as a marker of worsening residual renal function in critically ill patients with severe AKI. Design, setting, participants, & measurements The Acute Renal Failure Trial Network Study (n=1124) was a multicenter trial that randomized critically ill patients requiring initiation of RRT to more intensive (hemodialysis or sustained low-efficiency dialysis six times per week or continuous venovenous hemodiafiltration at 35 ml/kg per hour) versus less intensive (hemodialysis or sustained low-efficiency dialysis three times per week or continuous venovenous hemodiafiltration at 20 ml/kg per hour) RRT. Mixed linear regression models were fit to estimate the association of RRT intensity with change in daily urine output in survivors through day 7 (n=871); Cox regression models were fit to determine the association of RRT intensity with time to >= 50% decline in urine output in all patients through day 28. Results Mean age of participants was 60 +/- 15 years old, 72% were men, and 30% were diabetic. In unadjusted models, among patients who survived >= 7 days, mean urine output was, on average, 31.7 ml/d higher (95% confidence interval, 8.2 to 55.2 ml/d) for the less intensive group compared with the more intensive group (P=0.01). More intensive RRT was associated with 29% greater unadjusted risk of decline in urine output of >= 50% (hazard ratio, 1.29; 95% confidence interval, 1.10 to 1.51). Conclusions More intensive versus less intensive RRT is associated with a greater reduction in urine output during the first 7 days of therapy and a greater risk of developing a decline in urine output of >= 50% in critically ill patients with severe AKI. C1 [Mc Causland, Finnian R.; Waikar, Sushrut S.] Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA. [Mc Causland, Finnian R.; Waikar, Sushrut S.] Harvard Med Sch, Boston, MA USA. [Asafu-Adjei, Josephine] Univ North Carolina Chapel Hill, Sch Nursing, Dept Biostat, Chapel Hill, NC USA. [Betensky, Rebecca A.] Harvard Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Palevsky, Paul M.] Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA. RP Mc Causland, FR (reprint author), Brigham & Womens Hosp, MRB 4, Boston, MA 02446 USA. EM fmccausland@partners.org FU American Heart Association; NIDDK [DK102511, DK093574, DK075941, U01DK085660, R01DK103784]; Cooperative Studies Program of the Department of Veterans Affairs (VA) Office of Research and Development; NIDDK FX F.R.M. was supported by an American Heart Association award from 2014 to 2015 and is currently supported by NIDDK grant DK102511. S.S.W. is supported by NIDDK grants DK093574, DK075941, U01DK085660, and R01DK103784. The ATN Study was performed by the ATN Study investigators and supported by the Cooperative Studies Program of the Department of Veterans Affairs (VA) Office of Research and Development and the NIDDK. NR 36 TC 2 Z9 2 U1 1 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD AUG PY 2016 VL 11 IS 8 BP 1335 EP 1342 DI 10.2215/CJN.10991015 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA DY1BP UT WOS:000384830200006 PM 27449661 ER PT J AU Afkarian, M Katz, R Bansal, N Correa, A Kestenbaum, B Himmelfarb, J de Boer, IH Young, B AF Afkarian, Maryam Katz, Ronit Bansal, Nisha Correa, Adolfo Kestenbaum, Bryan Himmelfarb, Jonathan de Boer, Ian H. Young, Bessie TI Diabetes, Kidney Disease, and Cardiovascular Outcomes in the Jackson Heart Study SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; ALL-CAUSE MORTALITY; UNITED-STATES; COLLABORATIVE METAANALYSIS; ATHEROSCLEROSIS RISK; GENERAL-POPULATION; ETHNIC DISPARITIES; ALBUMINURIA; COMPLICATIONS; EPIDEMIOLOGY AB Background and objectives Blacks have high rates of cardiovascular disease and mortality. Diabetes and CKD, risk factors for cardiovascular mortality in the general population, are common among blacks. We sought to assess their contribution to cardiovascular disease and mortality in blacks. Design, setting, participants, & measurements This observational cohort study was of 3211 participants in the Jackson Heart Study (enrolled 2000-2004). Rates of incident stroke, incident coronary heart disease, and cardiovascular mortality were quantified in participants with diabetes, CKD (eGFR < 60 ml/min per 1.73 m(2), urine albumin-to-creatinine ratio >= 30 mg/g, or both), or both through 2012, with a median follow-up of 6.99 years. Results Four hundred fifty-six (14.2%) participants had only diabetes, 257 (8.0%) had only CKD, 201 (6.3%) had both, and 2297 (71.5%) had neither. Diabetes without CKD was associated with excess risks of incident stroke, incident coronary heart disease, and cardiovascular mortality after adjustment for demographic and clinical covariates, including prevalent cardiovascular disease (excess incidence rates, 2.6; 95% confidence interval, 0.5 to 4.7; 2.6; 95% confidence interval, 0.3 to 4.8; and 2.4; 95% confidence interval, 0.4 to 4.3 per 1000 person-years, respectively). CKD without diabetes was associated with comparable nonsignificant excess risks for incident stroke and coronary heart disease (2.5; 95% confidence interval, -0.1 to 5.2 and 2.4; 95% confidence interval, -0.8 to 5.5 per 1000 person-years, respectively) but a larger excess risk for cardiovascular mortality (7.3; 95% confidence interval, 3.0 to 11.5 per 1000 person-years). Diabetes and CKD together were associated with greater excess risks for incident stroke (13.8; 95% confidence interval, 5.3 to 22.3 per 1000 person-years), coronary heart disease (12.8; 95% confidence interval, 4.9 to 20.8 per 1000 person-years), and cardiovascular mortality (14.8; 95% confidence interval, 7.2 to 22.3 per 1000 person-years). The excess risks associated with the combination of diabetes and CKD were larger than those associated with established risk factors, including prevalent cardiovascular disease. Conclusions The combination of diabetes and kidney disease is associated with substantial excess risks of cardiovascular events and mortality among blacks. C1 [Afkarian, Maryam; Katz, Ronit; Bansal, Nisha; Kestenbaum, Bryan; Himmelfarb, Jonathan] Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA. [Afkarian, Maryam; Katz, Ronit; Bansal, Nisha; Kestenbaum, Bryan; Himmelfarb, Jonathan] Univ Washington, Div Nephrol, Seattle, WA 98195 USA. [Correa, Adolfo] Univ Mississippi, Med Ctr, Dept Med, Jackson Heart Study, Jackson, MS 39216 USA. [de Boer, Ian H.; Young, Bessie] Univ Washington, Kidney Res Inst, Div Nephrol, Vet Affairs Puget Sound, Seattle, WA 98195 USA. RP Afkarian, M (reprint author), Box 359606,325 9th Ave, Seattle, WA 98104 USA. EM afkarian@u.washington.edu FU National Institute of Diabetes, Digestive, and Kidney Disease (NIDDK) [K23DK089017, R01DK104706]; Satellite Healthcare; National Institutes of Health NIDDK [1R01DK102134-01]; NIDDK [R01DK087726, R01DK088762]; Veterans Affairs Puget Sound Health Care System (Seattle, WA); National Heart, Lung, and Blood Institute [HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C]; National Institute on Minority Health and Health Disparities FX M.A. was supported by grants K23DK089017 and R01DK104706 from the National Institute of Diabetes, Digestive, and Kidney Disease (NIDDK) and a Norman S. Coplon Extramural Grant from Satellite Healthcare. R.K., I.H.d.B., and B.Y. were supported by National Institutes of Health NIDDK grant 1R01DK102134-01. I.H.d.B. was supported by grants R01DK087726 and R01DK088762 from the NIDDK. I.H.d.B. and B.Y. are also supported, in part, by funding from the Veterans Affairs Puget Sound Health Care System (Seattle, WA). The Jackson Heart Study is supported by contracts HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, and HHSN268201300050C from the National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities. NR 40 TC 3 Z9 3 U1 1 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD AUG PY 2016 VL 11 IS 8 BP 1384 EP 1391 DI 10.2215/CJN.13111215 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA DY1BP UT WOS:000384830200012 PM 27340284 ER PT J AU Mair, CA Quinones, AR Pasha, MA AF Mair, Christine A. Quinones, Ana R. Pasha, Maha A. TI Care Preferences Among Middle-Aged and Older Adults With Chronic Disease in Europe: Individual Health Care Needs and National Health Care Infrastructure SO GERONTOLOGIST LA English DT Article DE Caregiving-informal; Caregiving-formal; Health care policy ID LONG-TERM-CARE; PUBLIC-ATTITUDES; FAMILY CAREGIVERS; WELFARE-STATE; NURSING-HOME; PERCEPTIONS; DEMENTIA; CONTEXTS; POLICIES; MODERATE AB Purpose of the Study: The purpose of this study is to expand knowledge of care options for aging populations cross-nationally by examining key individual-level and nation-level predictors of European middle-aged and older adults' preferences for care. Design and Methods: Drawing on data from the Survey of Health, Ageing and Retirement in Europe and the Organisation for Economic Co-operation and Development, we analyze old age care preferences of a sample of 6,469 adults aged 50 and older with chronic disease in 14 nations. Using multilevel modeling, we analyze associations between individual-level health care needs and nation-level health care infrastructure and preference for family-based (vs. state-based) personal care. Results: We find that middle-aged and older adults with chronic disease whose health limits their ability to perform paid work, who did not receive personal care from informal sources, and who live in nations with generous long-term care funding are less likely to prefer family-based care and more likely to prefer state-based care. Implications: We discuss these findings in light of financial risks in later life and the future role of specialized health support programs, such as long-term care. C1 [Mair, Christine A.] Univ Maryland Baltimore Cty, Dept Sociol & Anthropol, 1000 Hilltop Circle, Baltimore, MD 21250 USA. [Quinones, Ana R.; Pasha, Maha A.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland VA Med Ctr, Portland, OR 97201 USA. RP Mair, CA (reprint author), Univ Maryland Baltimore Cty, Dept Sociol & Anthropol, 1000 Hilltop Circle, Baltimore, MD 21250 USA. EM christine_mair@umbc.edu FU NHLBI NIH HHS [R25 HL105430] NR 38 TC 1 Z9 1 U1 3 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD AUG PY 2016 VL 56 IS 4 BP 687 EP 701 DI 10.1093/geront/gnu119 PG 15 WC Gerontology SC Geriatrics & Gerontology GA DY0AU UT WOS:000384760000012 PM 26035873 ER PT J AU Thompson, B Molina, Y Viswanath, K Warnecke, R Prelip, ML AF Thompson, Beti Molina, Yamile Viswanath, Kasisomayajula Warnecke, Richard Prelip, Michael L. TI Strategies To Empower Communities To Reduce Health Disparities SO HEALTH AFFAIRS LA English DT Article ID OF-THE-LITERATURE; PARTICIPATORY RESEARCH; PROMOTION AB Community-based participatory research is a promising approach to reducing health disparities. It empowers individuals and communities to become the major players in solving their own health problems. We discuss the use of community-based participatory research and other strategies to enhance empowerment. We also discuss projects from the Centers for Population Health and Health Disparities that have empowered communities to achieve positive health outcomes aimed at reducing disparities. We offer recommendations to policy makers for involving residents in efforts to achieve health equity. C1 [Thompson, Beti; Molina, Yamile] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, 1124 Columbia St, Seattle, WA 98104 USA. [Viswanath, Kasisomayajula] Dana Farber Canc Inst, Dept Med Oncol, Popular Sci, Boston, MA 02115 USA. [Viswanath, Kasisomayajula] Harvard TH Chan Sch Publ Hlth, Human Dev & Hlth, Boston, MA USA. [Warnecke, Richard] Univ Illinois, Ctr Hlth Policy, Chicago, IL USA. [Prelip, Michael L.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Community Hlth Sci, Los Angeles, CA USA. RP Thompson, B (reprint author), Fred Hutchinson Canc Res Ctr, Canc Prevent Program, 1124 Columbia St, Seattle, WA 98104 USA. EM bthompso@fhcrc.org FU NCI NIH HHS [U54 CA203000, P50 CA148143, U54 CA202995, R25 CA092408, U54 CA202997] NR 30 TC 2 Z9 2 U1 1 U2 1 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD AUG PY 2016 VL 35 IS 8 BP 1424 EP 1428 DI 10.1377/hlthaff.2015.1364 PG 5 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA DY0QO UT WOS:000384801500013 PM 27503967 ER PT J AU Kato, S Lippman, SM Flaherty, KT Kurzrock, R AF Kato, Shumei Lippman, Scott M. Flaherty, Keith T. Kurzrock, Razelle TI The Conundrum of Genetic "Drivers" in Benign Conditions SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID CELL LUNG-CANCER; TUMOR-SUPPRESSOR GENE; CONGENITAL MELANOCYTIC NEVI; GROWTH-FACTOR RECEPTOR-3; INFLAMMATORY MYOFIBROBLASTIC TUMORS; ONCOGENE-INDUCED SENESCENCE; INTEGRATED GENOMIC ANALYSIS; TYROSINE KINASE INHIBITOR; DOSE-ESCALATION TRIAL; CARCINOMA IN-SITU AB Advances in deep genomic sequencing have identified a spectrum of cancer-specific passenger and driver aberrations. Clones with driver anomalies are believed to be positively selected during carcinogenesis. Accumulating evidence, however, shows that genomic alterations, such as those in BRAF, RAS, EGFR, HER2, FGFR3, PIK3CA, TP53, CDKN2A, and NF1/2, all of which are considered hallmark drivers of specific cancers, can also be identified in benign and premalignant conditions, occasionally at frequencies higher than in their malignant counterparts. Targeting these genomic drivers can produce dramatic responses in advanced cancer, but the effects on their benign counterparts are less clear. This benign-malignant phenomenon is well illustrated in studies of BRAF V600E mutations, which are paradoxically more frequent in benign nevi (similar to 80%) than in dysplastic nevi (similar to 60%) or melanoma (similar to 40%-45%). Similarly, human epidermal growth factor receptor 2 is more commonly overexpressed in ductal carcinoma in situ (similar to 27%-56%) when compared with invasive breast cancer (similar to 11%-20%). FGFR3 mutations in bladder cancer also decrease with tumor grade (low-grade tumors, similar to 61%; high-grade, similar to 11%). "Driver" mutations also occur in nonmalignant settings: TP53 mutations in synovial tissue from rheumatoid arthritis and FGFR3 mutations in seborrheic keratosis. The latter observations suggest that the oncogenicity of these alterations may be tissue context-dependent. The conversion of benign conditions to premalignant disease may involve other genetic events and/or epigenetic reprogramming. Putative driver mutations can also be germline and associated with increased cancer risk (eg, germline RAS or TP53 alterations), but germline FGFR3 or NF2 abnormalities do not predispose to malignancy. We discuss the enigma of genetic "drivers" in benign and premalignant conditions and the implications for prevention strategies and theories of tumorigenesis. C1 [Kato, Shumei] Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, 1400 Holcombe Blvd, Houston, TX 77030 USA. [Lippman, Scott M.; Kurzrock, Razelle] Univ Calif San Diego, Moores Canc Ctr, Ctr Personalized Canc Therapy, La Jolla, CA USA. [Lippman, Scott M.; Kurzrock, Razelle] Univ Calif San Diego, Moores Canc Ctr, Div Hematol & Oncol, La Jolla, CA USA. [Flaherty, Keith T.] Massachusetts Gen Hosp, Ctr Canc, Henri & Belinda Termeer Ctr Targeted Therapies, Boston, MA USA. RP Kato, S (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, 1400 Holcombe Blvd, Houston, TX 77030 USA.; Lippman, SM (reprint author), Univ Calif San Diego, Moores Canc Ctr, 3855 Hlth Sci Dr 0658, La Jolla, CA 92093 USA. EM shumei.kato@gmail.com; slippman@ucsd.edu FU Joan and Irwin Jacobs philanthropic fund; National Cancer Institute [P30 CA016672-36] FX Funded in part by the Joan and Irwin Jacobs philanthropic fund (Razelle Kurzrock) and National Cancer Institute grant P30 CA016672-36 (Scott M. Lippman and Razelle Kurzrock). NR 192 TC 4 Z9 4 U1 3 U2 3 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 AUG PY 2016 VL 108 IS 8 AR djw036 DI 10.1093/jnci/djw036 PG 13 WC Oncology SC Oncology GA DY3UD UT WOS:000385019300011 ER PT J AU Post, RM Kupka, R Keck, PE McElroy, SL Altshuler, LL Frye, MA Rowe, M Grunze, H Suppes, T Leverich, GS Nolen, WA AF Post, Robert M. Kupka, Ralph Keck, Paul E., Jr. McElroy, Susan L. Altshuler, Lori L. Frye, Mark A. Rowe, Michael Grunze, Heinz Suppes, Trisha Leverich, Gabriele S. Nolen, Willem A. TI Further Evidence of a Cohort Effect in Bipolar Disorder: More Early Onsets and Family History of Psychiatric Illness in More Recent Epochs SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article DE Bipolar Disorder ID AGE-OF-ONSET; MENTAL-HEALTH-SURVEY; MOOD-DISORDERS; LIFETIME PREVALENCE; UNITED-STATES; BIRTH-COHORT; AT-ONSET; PARENTS; RISK; METAANALYSIS AB Objective: Given that a cohort effect is rarely mentioned as one of the possible contributors to the increased incidence of childhood-onset bipolar disorder in the United States, we reexamined evidence for the phenomenon within our outpatient Bipolar Collaborative Network. Methods: 968 outpatients (mean age, 41 years) with DSM bipolar disorder from 1995 to 2002 from 4 sites in the United States and 3 in the Netherlands and Germany (abbreviated as Europe) gave informed consent and provided detailed demographic, illness, and family history information on a patient questionnaire. Family history of bipolar disorder, depression, suicide attempt, alcohol abuse, substance abuse, and "other" illness was collected for each parent and the 4 grandparents. Age at onset and family history of illness burden were then assessed as a function of the age of the patient at network entry. Results: Data for patients aged 35 years or older (n = 613) were included in the first analysis. Compared to older patients, those who were younger when they entered the network had an earlier age at onset of their bipolar disorder (r = 0.33, P < .001). Similarly, the youngest patients at entry (representing the most recent cohorts) had parents and grandparents with more psychiatric illness than patients born in earlier cohorts (n = 968). Conclusions: These preliminary data, taken with the substantial literature, suggest a cohort effect for earlier age at onset of bipolar disorder and greater burden of psychiatric disorders in 2 generations of direct progenitors of our patients. The resulting likely increase in severity of bipolar illness in future generations based on this earlier age at onset and increased familial loading, particularly in the United States, deserves focused clinical and public health attention and attempts at amelioration. 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. [Kupka, Ralph] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands. [Keck, Paul E., Jr.] Univ Cincinnati, Dept Psychiat & Behav Neurosci, Coll Med, Cincinnati, OH 45221 USA. [Keck, Paul E., Jr.; McElroy, Susan L.] Lindner Ctr HOPE, Mason, OH USA. [McElroy, Susan L.] Univ Cincinnati, Biol Psychiat Program, Coll Med, Cincinnati, OH 45221 USA. [Altshuler, Lori L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Altshuler, Lori L.] VA Greater Los Angeles Healthcare Syst, Dept Psychiat, West Los Angeles Healthcare Ctr, Los Angeles, CA USA. [Frye, Mark A.] Mayo Clin, Dept Psychiat & Psychol, Rochester, MN USA. [Grunze, Heinz] Newcastle Univ, Inst Neurosci & Campus Aging & Vital, Wolfson Res Ctr, Newcastle Upon Tyne, 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. [Nolen, Willem A.] Univ Groningen, Univ Med Ctr Groningen, NL-9700 AB Groningen, Netherlands. RP Post, RM (reprint author), 5415 W Cedar Ln,Ste 201-B, Bethesda, MD 20814 USA. EM robert.post@speakeasy.net OI Grunze, Heinz/0000-0003-4712-8979 FU Stanley Medical Research Institute FX Support was provided by the Stanley Medical Research Institute from 1995-2002. NR 47 TC 3 Z9 3 U1 5 U2 5 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 AUG PY 2016 VL 77 IS 8 BP 1043 EP 1049 DI 10.4088/JCP.15m10121 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DY0OO UT WOS:000384796300017 PM 27379705 ER PT J AU Yeung, A Martinson, MA Baer, L Chen, J Clain, A Williams, A Chang, TE Trinh, NHT Alpert, JE Fava, M AF Yeung, Albert Martinson, Max A. Baer, Lee Chen, Justin Clain, Alisabet Williams, Aya Chang, Trina E. Trinh, Nhi-Ha T. Alpert, Jonathan E. Fava, Maurizio TI The Effectiveness of Telepsychiatry-Based Culturally Sensitive Collaborative Treatment for Depressed Chinese American Immigrants: A Randomized Controlled Trial SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article DE Cross-Cultural Psychiatry; Depression ID OF-LIFE ENJOYMENT; PRIMARY-CARE; ASIAN-AMERICANS; RATING-SCALE; SATISFACTION QUESTIONNAIRE; HEALTH; OUTCOMES; EPIDEMIOLOGY; RELIABILITY; DISPARITIES AB Objective: This study evaluates the effectiveness of a telepsychiatry-based culturally sensitive collaborative treatment (T-CSCT) intervention to improve treatment outcomes for depressed Chinese American immigrants. Methods: Participants were Chinese Americans recruited from primary care settings from February 1, 2009, to July 31, 2012, with DSM-IV major depressive disorder (MDD) identified by the Mini-International Neuropsychiatric Interview. Eligible patients were randomized to receive either T-CSCT or treatment as usual (TAU) for 6 months. T-CSCT involves (1) cultural consultation via videoconference and (2) care management. The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS17); positive response was defined as a >= 50% decrease in HDRS17 score, and remission was defined as HDRS17 score <= 7. Secondary outcome measures were the Clinical Global Impressions-Severity of Illness (CGI-S) and Improvement (CGI-I) scales and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Outcomes were compared using multivariate logistic regression and mixedmodel for repeated measures methods. Results: Among participants (N = 190), 63% were female, and the mean (SD) age was 50 (14.5) years. They were randomized to T-CSCT (n = 97; 51%) or TAU (n = 93; 49%). Using multivariate logistic regression analyses, the odds of achieving response and remission were significantly greater for the T-CSCT group compared to the control group (odds ratio [OR] = 3.9 [95% CI, 1.9 to 7.8] and 4.4 [95% CI, 1.9 to 9.9], respectively). Multivariate general linear model analyses showed that patients in the T-CSCT group had significantly greater improvement over time in HDRS17 (F-4,F-95 = 4.59, P = .002), CGI-S (F4,95 = 4.22, P = .003), and CGI-I (F-4,F-95 = 2.95, P = .02) scores. Conclusions: T-CSCT is effective in improving treatment outcomes of Chinese immigrants with MDD. C1 [Yeung, Albert; Martinson, Max A.; Baer, Lee; Chen, Justin; Clain, Alisabet; Williams, Aya; Chang, Trina E.; Trinh, Nhi-Ha T.; Alpert, Jonathan E.; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, 1 Bowdoin Sq, Boston, MA 02114 USA. [Yeung, Albert] South Cove Community Hlth Ctr, Boston, MA USA. RP Yeung, A (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 1 Bowdoin Sq, Boston, MA 02114 USA. EM ayeung@partners.org FU National Institutes of Health (NIH) [R01 MH079831]; National Institutes of Health (Bethesda, Maryland) [R01 MH079831] FX The study was supported by the National Institutes of Health (NIH; Bethesda, Maryland) grant R01 MH079831 and is registered on ClinicalTrials.gov (NCT00854542). NR 41 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 AUG PY 2016 VL 77 IS 8 BP E996 EP E1002 DI 10.4088/JCP.15m09952 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DY0OO UT WOS:000384796300006 PM 27561153 ER PT J AU Williams, WW Delmonico, FL AF Williams, Winfred W. Delmonico, Francis L. TI The End of Racial Disparities in Kidney Transplantation? Not So Fast! SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID DECEASED DONOR KIDNEYS; DISEASE; VARIANTS; ACCESS; APOL1 C1 [Williams, Winfred W.] Harvard Med Sch, Massachusetts Gen Hosp, Transplant Ctr, Div Nephrol, Boston, MA USA. [Delmonico, Francis L.] Harvard Med Sch, Massachusetts Gen Hosp, Transplant Ctr, Dept Surg, Boston, MA USA. RP Williams, WW (reprint author), Massachusetts Gen Hosp, Transplant Ctr, 165 Cambridge St,Suite 302, Boston, MA 02114 USA.; Williams, WW (reprint author), Massachusetts Gen Hosp, Div Nephrol, 165 Cambridge St,Suite 302, Boston, MA 02114 USA. EM wwwilliams@mgh.harvard.edu NR 13 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD AUG PY 2016 VL 27 IS 8 BP 2224 EP 2226 DI 10.1681/ASN.2016010005 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA DY3PM UT WOS:000385006100004 PM 26952001 ER PT J AU Lu, Y Wei, J Stec, DE Roman, RJ Ge, Y Cheng, L Liu, EY Zhang, J Hansen, PBL Fan, F Juncos, LA Wang, L Pollock, J Huang, PL Fu, YL Wang, SH Liu, RS AF Lu, Yan Wei, Jin Stec, David E. Roman, Richard J. Ge, Ying Cheng, Liang Liu, Eddie Y. Zhang, Jie Hansen, Pernille B. Laerkegaard Fan, Fan Juncos, Luis A. Wang, Lei Pollock, Jennifer Huang, Paul L. Fu, Yiling Wang, Shaohui Liu, Ruisheng TI Macula Densa Nitric Oxide Synthase 1 beta Protects against Salt-Sensitive Hypertension SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID II-INDUCED HYPERTENSION; TUBULOGLOMERULAR FEEDBACK; BLOOD-PRESSURE; RAT-KIDNEY; COLLECTING DUCT; DIETARY SALT; ANGIOTENSIN; ISOFORMS; CELLS; HEART AB Nitric oxide (NO) is an important negative modulator of tubuloglomerular feedback responsiveness. We recently found that macula densa expresses alpha-, beta-, and gamma-splice variants of neuronal nitric oxide synthase 1 (NOS1), and NOS1 beta expression in the macula densa increases on a high-salt diet. This study tested whether upregulation of NOS1 beta expression in the macula densa affects sodium excretion and salt-sensitive hypertension by decreasing tubuloglomerular feedback responsiveness. Expression levels of NOS1 beta mRNA and protein were 30- and five-fold higher, respectively, than those of NOS1 alpha in the renal cortex of C57BL/6 mice. Furthermore, macula densa NO production was similar in the isolated perfused juxtaglomerular apparatus of wild-type (WT) and nitric oxide synthase 1 alpha-knockout (NOS1 alpha KO) mice. Compared with control mice, mice with macula densa-specific knockout of all nitric oxide synthase 1 isoforms (MD-NOS1KO) had a significantly enhanced tubuloglomerular feedback response and after acute volume expansion, significantly reduced GFR, urine flow, and sodium excretion. Mean arterial pressure increased significantly in MD-NOS1KO mice (P < 0.01) but not NOS1flox/flox mice fed a high-salt diet. After infusion of angiotensin II, mean arterial pressure increased by 61.6 mmHg in MD-NOS1KO mice versus 32.0 mmHg in WT mice (P < 0.01) fed a high-salt diet. These results indicate that NOS1 beta is a primary NOS1 isoform expressed in the macula densa and regulates the tubuloglomerular feedback response, the natriuretic response to acute volume expansion, and the development of salt-sensitive hypertension. These findings show a novel mechanism for salt sensitivity of BP and the significance of tubuloglomerular feedback response in long-term control of sodium excretion and BP. C1 [Lu, Yan; Wei, Jin; Zhang, Jie; Wang, Lei; Wang, Shaohui; Liu, Ruisheng] Univ S Florida, Coll Med, Dept Mol Pharmacol & Physiol, 12901 Bruce B Downs Blvd,MDC 8, Tampa, FL 33612 USA. [Lu, Yan; Stec, David E.; Cheng, Liang; Liu, Eddie Y.; Juncos, Luis A.; Fu, Yiling; Liu, Ruisheng] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA. [Roman, Richard J.; Ge, Ying; Fan, Fan] Univ Mississippi, Med Ctr, Dept Pharmacol, Jackson, MS 39216 USA. [Hansen, Pernille B. Laerkegaard] Univ Southern Denmark, Dept Cardiovasc & Renal Res, Odense, Denmark. [Pollock, Jennifer] Univ Alabama Birmingham, Dept Med, Div Nephrol, Birmingham, AL 35294 USA. [Huang, Paul L.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. RP Liu, RS (reprint author), Univ S Florida, Coll Med, Dept Mol Pharmacol & Physiol, 12901 Bruce B Downs Blvd,MDC 8, Tampa, FL 33612 USA. EM ruisheng@health.usf.edu FU National Institutes of Health [DK104184, DK099276, DK098582, P01HL051971] FX This work was supported by National Institutes of Health Grants DK104184 (to R.J.R.), DK099276 (to R.L.), DK098582 (to R.L.), and P01HL051971 (to core facility). NR 53 TC 5 Z9 5 U1 3 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD AUG PY 2016 VL 27 IS 8 BP 2346 EP 2356 DI 10.1681/ASN.2015050515 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA DY3PM UT WOS:000385006100016 PM 26647426 ER PT J AU Naimark, DMJ Grams, ME Matsushita, K Black, C Drion, I Fox, CS Inker, LA Ishani, A Jee, SH Kitamura, A Lea, JP Nally, J Peralta, CA Rothenbacher, D Ryu, S Tonelli, M Yatsuya, H Coresh, J Gansevoort, RT Warnock, DG Woodward, M de Jong, PE AF Naimark, David M. J. Grams, Morgan E. Matsushita, Kunihiro Black, Corri Drion, Iefke Fox, Caroline S. Inker, Lesley A. Ishani, Areef Jee, Sun Ha Kitamura, Akihiko Lea, Janice P. Nally, Joseph Peralta, Carmen Alicia Rothenbacher, Dietrich Ryu, Seungho Tonelli, Marcello Yatsuya, Hiroshi Coresh, Josef Gansevoort, Ron T. Warnock, David G. Woodward, Mark de Jong, Paul E. CA CKD Prognosis Consortium TI Past Decline Versus Current eGFR and Subsequent Mortality Risk SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; STAGE RENAL-DISEASE; COLLABORATIVE METAANALYSIS; POPULATION COHORTS; HIGHER ALBUMINURIA; ALL-CAUSE; CARDIOVASCULAR-DISEASE; DEATH; EQUATION AB A single determination of eGFR associates with subsequent mortality risk. Prior decline in eGFR indicates loss of kidney function, but the relationship to mortality risk is uncertain. We conducted an individual-level meta-analysis of the risk of mortality associated with antecedent eGFR slope, adjusting for established risk factors, including last eGFR, among 1.2 million subjects from 12 CKD and 22 other cohorts within the CKD Prognosis Consortium. Over a 3-year antecedent period, 12% of participants in the CKD cohorts and 11% in the other cohorts had an eGFR slope, <-5 ml/min per 1.73 m(2) per year, whereas 7% and 4% had a slope >5 ml/min per 1.73 m(2) per year, respectively. Compared with a slope of 0 ml/min per 1.73 m(2) per year, a slope of -6 ml/min per 1.73 m(2) per year associated with adjusted hazard ratios for all-cause mortality of 1.25 (95% confidence interval [95% CI], 1.09 to 1.44) among CKD cohorts and 1.15 (95% CI, 1.01 to 1.31) among other cohorts during a follow-up of 3.2 years. A slope of +6 ml/min per 1.73 m(2) per year also associated with higher all-cause mortality risk, with adjusted hazard ratios of 1.58 (95% CI, 1.29 to 1.95) among CKD cohorts and 1.43 (95% CI, 1.11 to 1.84) among other cohorts. Results were similar for cardiovascular and noncardiovascular causes of death and stronger for longer antecedent periods (3 versus <3 years). We conclude that prior decline or rise in eGFR associates with an increased risk of mortality, independent of current eGFR. C1 [Naimark, David M. J.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Div Nephrol, Toronto, ON, Canada. [Naimark, David M. J.] Univ Toronto, Fac Med, Inst Hlth Policy Management & Evaluat, Toronto, ON, Canada. [Grams, Morgan E.; Matsushita, Kunihiro; Coresh, Josef; Woodward, Mark] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Grams, Morgan E.] Johns Hopkins Univ, Dept Med, Div Nephrol, Baltimore, MD USA. [Black, Corri] Univ Aberdeen, Inst Appl Hlth Sci, Aberdeen, Scotland. [Drion, Iefke] Isala Clin, Ctr Diabet, Zwolle, Netherlands. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Ctr Populat Studies, Framingham, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, 75 Francis St, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Med Sch, Boston, MA USA. [Inker, Lesley A.] Tufts Med Ctr, Div Nephrol, Boston, MA USA. [Ishani, Areef] Minneapolis Vet Affairs Hlth Care Syst, Nephrol Sect, Minneapolis, MN USA. [Jee, Sun Ha] Yonsei Univ, Inst Hlth Promot, Grad Sch Publ Hlth, Dept Epidemiol & Hlth Promot, Seoul, South Korea. [Kitamura, Akihiko] Osaka Ctr Canc & Cardiovasc Dis Prevent, Osaka, Japan. [Lea, Janice P.] Emory Univ, Sch Med, Div Renal, Atlanta, GA 30322 USA. [Nally, Joseph] Glickman Urol & Kidney Inst, Dept Hypertens & Nephrol, Cleveland, OH USA. [Peralta, Carmen Alicia] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Peralta, Carmen Alicia] San Francisco VA Med Ctr, San Francisco, CA USA. [Rothenbacher, Dietrich] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Rothenbacher, Dietrich] Univ Ulm, Inst Epidemiol & Med Biometry, Ulm, Germany. [Ryu, Seungho] Sunkgyunkwan Univ, Sch Med, Kangbuk Samsung Hosp, Seoul, South Korea. [Tonelli, Marcello] Univ Calgary, Dept Med, Calgary, AB, Canada. [Yatsuya, Hiroshi] Fujita Hlth Univ, Dept Publ Hlth, Toyoake, Aichi, Japan. [Gansevoort, Ron T.; de Jong, Paul E.] Univ Groningen, Univ Med Ctr Groningen, Dept Nephrol, Groningen, Netherlands. [Warnock, David G.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Woodward, Mark] Univ Oxford, Nuffield Dept Populat Hlth, George Inst Global Hlth, Oxford, England. [Woodward, Mark] Univ Sydney, George Inst Global Hlth, Sydney, NSW, Australia. RP Coresh, J (reprint author), Chron Kidney Dis Prognosis Consortium, Data Coordinating Ctr, 2024 East Monument St, Baltimore, MD 21287 USA. EM ckdpc@jhmi.edu RI Tonelli, Marcello/B-3028-2009; Brenner, Hermann/B-4627-2017 OI Brenner, Hermann/0000-0002-6129-1572 FU US National Kidney Foundation; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK100446-01]; National Institutes of Health FX The Chronic Kidney Disease Prognosis Consortium (CKD-PC) Data Coordinating Center is funded, in part, by a program grant from the US National Kidney Foundation (funding sources include AbbVie and Amgen, Inc.) and National Institute of Diabetes and Digestive and Kidney Diseases Grant R01DK100446-01. A variety of sources have supported enrollment and data collection, including laboratory measurements, as well as follow-up in the collaborating cohorts of the CKD-PC. These funding sources include government agencies, such as the National Institutes of Health, and medical research councils as well as foundations and industry sponsors, and they are listed in Supplemental Appendix 3. Individual cohort and collaborator support is listed in Supplemental Appendix 3. NR 29 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD AUG PY 2016 VL 27 IS 8 BP 2456 EP 2466 DI 10.1681/ASN.2015060688 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA DY3PM UT WOS:000385006100025 PM 26657865 ER PT J AU Schirda, CV Zhao, TJ Andronesi, OC Lee, Y Pan, JW Mountz, JM Hetherington, HP Boada, FE AF Schirda, Claudiu V. Zhao, Tiejun Andronesi, Ovidiu C. Lee, Yoojin Pan, Jullie W. Mountz, James M. Hetherington, Hoby P. Boada, Fernando E. TI In Vivo Brain Rosette Spectroscopic Imaging (RSI) with LASER Excitation, Constant Gradient Strength Readout, and Automated LCModel Quantification for all Voxels SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE fast spectroscopic imaging; normalized SNR efficiency; Rosette trajectories; RSI; sensitivity; LASER; brain ID K-SPACE TRAJECTORIES; PHASED-ARRAY COILS; REAL-TIME MOTION; CHEMICAL-SHIFT; MR SPECTROSCOPY; SINGLE-SHOT; ACQUISITION; NMR; REDUCTION; ARTIFACTS AB Purpose: To optimize the Rosette trajectories for high-sensitivity in vivo brain spectroscopic imaging and reduced gradient demands. Methods: Using LASER localization, a rosette based sampling scheme for in vivo brain spectroscopic imaging data on a 3 Tesla (T) system is described. The two-dimensional (2D) and 3D rosette spectroscopic imaging (RSI) data were acquired using 20 x 20 in-plane resolution (8 x 8 mm(2)), and 1 (2D) -18 mm (1.1 cc) or 12 (3D) -8 mm partitions (0.5 cc voxels). The performance of the RSI acquisition was compared with a conventional spectroscopic imaging (SI) sequence using LASER localization and 2D or 3D elliptical phase encoding (ePE). Quantification of the entire RSI data set was performed using an LCModel based pipeline. Results: The RSI acquisitions took 32 s for the 2D scan, and as short as 5 min for the 3D 20 x 20 x 12 scan, using a maximum gradient strength G(max) = 5.8 mT/m and slew-rate S-max = 45 mT/m/ms. The Bland-Altman agreement between RSI and ePE CSI, characterized by the 95% confidence interval for their difference (RSI-ePE), is within 13% of the mean (RSI+ePE)/2. Compared with the 3D ePE at the same nominal resolution, the effective RSI voxel size was three times smaller while the measured signal-to-noise ratio sensitivity, after normalization for differences in effective size, was 43% greater. Conclusio n: 3D LASER-RSI is a fast, high-sensitivity spectroscopic imaging sequence, which can acquire medium-to-high resolution SI data in clinically acceptable scan times (5-10 min), with reduced stress on the gradient system. (C) 2015 Wiley Periodicals, Inc. C1 [Schirda, Claudiu V.; Lee, Yoojin; Pan, Jullie W.; Mountz, James M.; Hetherington, Hoby P.] Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA USA. [Zhao, Tiejun] Siemens Med Solutions USA Inc, Siemens Healthcare, Pittsburgh, PA USA. [Andronesi, Ovidiu C.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Pan, Jullie W.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Boada, Fernando E.] NYU, Dept Radiol, 560 1St Ave, New York, NY 10016 USA. RP Schirda, CV (reprint author), Univ Pittsburgh, Sch Med, MRRC, UPMC, 200 Lothrop St,PUH B824, Pittsburgh, PA 15213 USA. EM claudiu.schirda@gmail.com OI Schirda, Claudiu/0000-0002-5036-0640 FU National Institutes of Health [1R01EB011639, 1R01NS081772, 1R01NS090417, R01-EB009871, U01 CA140230]; University of Pittsburgh Cancer Institute In Vivo Imaging Facility [P30CA047904] FX Grant sponsor: National Institutes of Health; Grant numbers: 1R01EB011639, 1R01NS081772, 1R01NS090417, R01-EB009871, U01 CA140230; Grant sponsor: University of Pittsburgh Cancer Institute In Vivo Imaging Facility; Grant number: P30CA047904. NR 45 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD AUG PY 2016 VL 76 IS 2 BP 380 EP 390 DI 10.1002/mrm.25896 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DY3MR UT WOS:000384997900002 PM 26308482 ER PT J AU Guerin, B Stockmann, JP Baboli, M Torrado-Carvajal, A Stenger, AV Wald, LL AF Guerin, Bastien Stockmann, Jason P. Baboli, Mehran Torrado-Carvajal, Angel Stenger, Andrew V. Wald, Lawrence L. TI Robust Time-Shifted Spoke Pulse Design in the Presence of Large B0 Variations with Simultaneous Reduction of Through-Plane Dephasing, B1+Effects, and the Specific Absorption Rate Using Parallel Transmission SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE spokes; parallel transmission; B0 artefact; B1+homogeneity; specific absorption rate ID Z-SHIM METHOD; REDUCING SUSCEPTIBILITY ARTIFACTS; TAILORED RF PULSES; FUNCTIONAL MRI; HUMAN BRAIN; GRADIENT COMPENSATION; IMAGE-RECONSTRUCTION; FIELD INHOMOGENEITY; SIGNAL LOSSES; GLOBAL SAR AB Purpose: To design parallel transmission spokes pulses with time-shifted profiles for joint mitigation of intensity variations due to B1+ effects, signal loss due to through-plane dephasing, and the specific absorption rate (SAR) at 7T. Methods: We derived a slice-averaged small tip angle (SA-STA) approximation of the magnetization signal at echo time that depends on the B1+ transmit profiles, the through-slice B0 gradient and the amplitude and time-shifts of the spoke waveforms. We minimize a magnitude least-squares objective based on this signal equation using a fast interior-point approach with analytical expressions of the Jacobian and Hessian. Results: Our algorithm runs in less than three minutes for the design of two-spoke pulses subject to hundreds of local SAR constraints. On a B0/B1+ head phantom, joint optimization of the channel-dependent time-shifts and spoke amplitudes allowed signal recovery in high-B0 regions at no increase of SAR. Although the method creates uniform magnetization profiles (ie, uniform intensity), the flip angle varies across the image, which makes it ill-suited to T1-weighted applications. Conclusions: The SA-STA approach presented in this study is best suited to T2*-weighted applications with long echo times that require signal recovery around high B0 regions. (C) 2015 Wiley Periodicals, Inc. C1 [Guerin, Bastien; Stockmann, Jason P.; Wald, Lawrence L.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [Stockmann, Jason P.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. [Baboli, Mehran; Stenger, Andrew V.] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. [Torrado-Carvajal, Angel] Univ Rey Juan Carlos, Med Image Anal & Biometry Lab, Mostoles, Spain. [Torrado-Carvajal, Angel] Madrid MIT M Vis Consortium, Madrid, Spain. [Wald, Lawrence L.] Harvard MIT Div Hlth Sci Technol, Cambridge, MA USA. RP Guerin, B (reprint author), 149 Thirteenth St,Suite 2301, Charlestown, MA 02129 USA. EM guerin@nmr.mgh.harvard.edu FU National Institutes of Health [R01-EB006847-08, P41-EB015896-17] FX Grant sponsor: National Institutes of Health; Grant numbers: R01-EB006847-08 and P41-EB015896-17. NR 39 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD AUG PY 2016 VL 76 IS 2 BP 540 EP 554 DI 10.1002/mrm.25902 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DY3MR UT WOS:000384997900017 PM 26444717 ER PT J AU Hauschild, A Chapman, PB Robert, C Larkin, J Haanen, JB Ribas, A Hogg, D Hamid, O Ascierto, PA Testori, A Lorigan, P Dummer, R Sosman, JA Flaherty, KT Wongchenko, MJ Yan, Y Chang, I Coleman, S Caro, I Mcarthur, GA AF Hauschild, A. Chapman, P. B. Robert, C. Larkin, J. Haanen, J. B. Ribas, A. Hogg, D. Hamid, O. Ascierto, P. A. Testori, A. Lorigan, P. Dummer, R. Sosman, J. A. Flaherty, K. T. Wongchenko, M. J. Yan, Y. Chang, I. Coleman, S. Caro, I. Mcarthur, G. A. TI Impact of key prognostic factors on long-term overall survival in BRAF(V600)-mutated metastatic melanoma patients treated with vemurafenib in the BRIM-3 study SO MELANOMA RESEARCH LA English DT Meeting Abstract C1 [Hauschild, A.] Univ Hosp Schleswig Holstein, Kiel, Germany. [Chapman, P. B.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Robert, C.] Inst Gustave Roussy, Paris, France. [Larkin, J.] Royal Marsden NHS Fdn Trust, London, England. [Haanen, J. B.] Netherlands Canc Inst, Amsterdam, Netherlands. [Ribas, A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Hogg, D.] Princess Margaret Hosp, Toronto, ON, Canada. [Hogg, D.] Univ Hlth Network, Toronto, ON, Canada. [Hamid, O.] Angeles Clin & Res Inst, Los Angeles, CA USA. [Ascierto, P. A.] Ist Nazl Tumori Fdn G Pascale, Naples, Italy. [Testori, A.] Ist Europeo Oncol, Milan, Italy. [Lorigan, P.] Univ Manchester, Manchester, Lancs, England. [Dummer, R.] Univ Zurich, Zurich, Switzerland. [Sosman, J. A.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Flaherty, K. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wongchenko, M. J.; Yan, Y.; Chang, I.; Coleman, S.; Caro, I.] Genentech Inc, San Francisco, CA 94080 USA. [Mcarthur, G. A.] Peter MacCallum Canc Ctr, East Melbourne, Australia. [Mcarthur, G. A.] Univ Melbourne, Parkville, Vic, Australia. 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 0960-8931 EI 1473-5636 J9 MELANOMA RES JI Melanoma Res. PD AUG PY 2016 VL 26 SU 1 MA P057 BP E39 EP E40 PG 2 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA DW3RR UT WOS:000383560800075 ER PT J AU Hauschild, A Larkin, J Ribas, A Dreno, B Flaherty, KT Ascierto, PA Lewis, KD Mckenna, E Zhu, Q Mun, Y Mcarthur, GA AF Hauschild, A. Larkin, J. Ribas, A. Dreno, B. Flaherty, K. T. Ascierto, P. A. Lewis, K. D. Mckenna, E. Zhu, Q. Mun, Y. Mcarthur, G. A. TI Identification of prognostic subgroups for overall survival in patients (pts) with BRAF(V600)-mutated metastatic melanoma treated with vemurafenib +/- cobimetinib: a pooled exploratory analysis of the BRIM-2, BRIM-3, BRIM-7, and coBRIM studies SO MELANOMA RESEARCH LA English DT Meeting Abstract C1 [Hauschild, A.] Univ Hosp Schleswig Holstein, Kiel, Germany. [Larkin, J.] Royal Marsden NHS Fdn Trust, London, England. [Ribas, A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Dreno, B.] Nantes Univ, Nantes, France. [Flaherty, K. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ascierto, P. A.] Fdn G Pascale, Ist Nazl Tumori, Naples, Italy. [Lewis, K. D.] Univ Colorado, Ctr Comprehens Canc, Aurora, CO USA. [Mckenna, E.; Zhu, Q.; Mun, Y.] Genentech Inc, San Francisco, CA 94080 USA. [Mcarthur, G. A.] Peter MacCallum Canc Ctr, East Melbourne, Australia. [Mcarthur, G. A.] Univ Melbourne, Parkville, Vic, Australia. 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 0960-8931 EI 1473-5636 J9 MELANOMA RES JI Melanoma Res. PD AUG PY 2016 VL 26 SU 1 MA SY8-5 BP E1 EP E2 PG 2 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA DW3RR UT WOS:000383560800003 ER PT J AU Schadendorf, D Larkin, J Chiarion-Sileni, V Gonzalez, R Rutkowski, P Grob, JJ Cowey, CL Lao, C Taylor, F Sabater, J Walker, D Bhore, R Wolchok, J Hodi, FS AF Schadendorf, D. Larkin, J. Chiarion-Sileni, V. Gonzalez, R. Rutkowski, P. Grob, J. -J. Cowey, C. L. Lao, C. Taylor, F. Sabater, J. Walker, D. Bhore, R. Wolchok, J. Hodi, F. S. TI Efficacy and quality of life outcomes in patients with advanced melanoma (MEL) who discontinued treatment with nivolumab (NIVO) plus ipilimumab (IPI) due to toxicity in a phase 3 trial (CheckMate 067) SO MELANOMA RESEARCH LA English DT Meeting Abstract C1 [Schadendorf, D.] Univ Hosp Essen, Dept Dermatol, Essen, Germany. [Larkin, J.] Royal Marsden Hosp, London, England. [Chiarion-Sileni, V.] Ist Oncol Veneto, Veneto, Italy. [Gonzalez, R.] Univ Colorado, Denver, CO USA. [Rutkowski, P.] Maria Sklodowska Curie Mem Canc Ctr, Warsaw, Poland. [Rutkowski, P.] Inst Oncol, Warsaw, Poland. [Grob, J. -J.] Hosp Timone, Marseille, France. [Cowey, C. L.] Texas Oncol Baylor Canc Ctr, Dallas, TX USA. [Lao, C.] Univ Michigan, Ann Arbor, MI 48109 USA. [Taylor, F.] Adelphi Values LTD, Boston, MA USA. [Sabater, J.; Walker, D.; Bhore, R.] Bristol Myers Squibb, Princeton, NJ USA. [Wolchok, J.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Hodi, F. S.] Dana Farber Canc Inst, Boston, MA 02115 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 0960-8931 EI 1473-5636 J9 MELANOMA RES JI Melanoma Res. PD AUG PY 2016 VL 26 SU 1 MA SY12-4 BP E4 EP E4 PG 1 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA DW3RR UT WOS:000383560800006 ER PT J AU Molinie, B Wang, JK Lim, KS Hillebrand, R Lu, ZX Van Wittenberghe, N Howard, BD Daneshvar, K Mullen, AC Dedon, P Xing, Y Giallourakis, CC AF Molinie, Benoit Wang, Jinkai Lim, Kok Seong Hillebrand, Roman Lu, Zhi-xiang Van Wittenberghe, Nicholas Howard, Benjamin D. Daneshvar, Kaveh Mullen, Alan C. Dedon, Peter Xing, Yi Giallourakis, Cosmas C. TI m(6)A-LAIC-seq reveals the census and complexity of the m(6)A epitranscriptome SO NATURE METHODS LA English DT Article ID MESSENGER-RNA METHYLATION; EMBRYONIC STEM-CELLS; SINGLE-NUCLEOTIDE-RESOLUTION; NUCLEIC-ACID MODIFICATIONS; LONG NONCODING RNA; ALTERNATIVE POLYADENYLATION; GENE-EXPRESSION; N-6-METHYLADENOSINE; SEQ; N6-METHYLADENOSINE AB N-6-Methyladenosine (m(6)A) is a widespread, reversible chemical modification of RNA molecules, implicated in many aspects of RNA metabolism. Little quantitative information exists as to either how many transcript copies of particular genes are m(6)A modified ('m(6)A levels') or the relationship of m(6)A modification(s) to alternative RNA isoforms. To deconvolute the m(6)A epitranscriptome, we developed m(6)A-level and isoform-characterization sequencing (m(6)A-LAIC-seq). We found that cells exhibit a broad range of nonstoichiometric m(6)A levels with cell-type specificity. At the level of isoform characterization, we discovered widespread differences in the use of tandem alternative polyadenylation (APA) sites by methylated and nonmethylated transcript isoforms of individual genes. Strikingly, there is a strong bias for methylated transcripts to be coupled with proximal APA sites, resulting in shortened 3' untranslated regions, while nonmethylated transcript isoforms tend to use distal APA sites. m(6)A-LAIC-seq yields a new perspective on transcriptome complexity and links APA usage to m(6)A modifications. C1 [Molinie, Benoit; Van Wittenberghe, Nicholas; Howard, Benjamin D.; Daneshvar, Kaveh; Mullen, Alan C.; Giallourakis, Cosmas C.] Harvard Med Sch, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02115 USA. [Wang, Jinkai; Lu, Zhi-xiang; Xing, Yi] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. [Lim, Kok Seong; Hillebrand, Roman; Dedon, Peter] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Giallourakis, Cosmas C.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Giallourakis, Cosmas C.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02115 USA. RP Giallourakis, CC (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02115 USA.; Xing, Y (reprint author), Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA.; Giallourakis, CC (reprint author), Harvard Stem Cell Inst, Cambridge, MA 02138 USA.; Giallourakis, CC (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02115 USA. EM yxing@ucla.edu; cgiallourakis@mgh.harvard.edu RI Lu, Zhixiang/G-4521-2014; OI Lu, Zhixiang/0000-0001-9230-2169; Daneshvar, Kaveh/0000-0002-7863-0489 FU MGH startup; ECOR grants; National Institutes of Health (NIH) [R01GM088342]; Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA; Rose Hills Foundation Research Award; Alfred Sloan Research Fellowship; National Research Foundation of Singapore through the Singapore-MIT Alliance for Research and Technology; National Institute of Environmental Health Science [ES002109, ES024615]; National Science Foundation [CHE-1308839]; NIH [DK090122] FX This study was supported by an MGH startup and ECOR grants to C.C.G. This study was also supported by National Institutes of Health (NIH) grant R01GM088342 and an Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA and Rose Hills Foundation Research Award to Y.X. Y.X. is supported by an Alfred Sloan Research Fellowship. P.D. was supported by the National Research Foundation of Singapore through the Singapore-MIT Alliance for Research and Technology, National Institute of Environmental Health Science grants ES002109 and ES024615, and National Science Foundation grant CHE-1308839. A.C.M. was supported by NIH grant DK090122. We thank D. Mirsky for copy editing the manuscript. We thank J. Wan for technical support on data analyses. We thank H. Chang, P. Batista, and K. Jeffrey for reading the manuscript and providing helpful comments. NR 55 TC 8 Z9 8 U1 9 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 EI 1548-7105 J9 NAT METHODS JI Nat. Methods PD AUG PY 2016 VL 13 IS 8 BP 692 EP + DI 10.1038/nmeth.3898 PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA DY6AT UT WOS:000385188700026 PM 27376769 ER PT J AU Zurnic, I Hutter, S Rzeha, U Stanke, N Reh, J Mullers, E Hamann, MV Kern, T Gerresheim, GK Lindel, F Serrao, E Lesbats, P Engelman, AN Cherepanov, P Lindemann, D AF Zurnic, Irena Huetter, Sylvia Rzeha, Ute Stanke, Nicole Reh, Juliane Muellers, Erik Hamann, Martin V. Kern, Tobias Gerresheim, Gesche K. Lindel, Fabian Serrao, Erik Lesbats, Paul Engelman, Alan N. Cherepanov, Peter Lindemann, Dirk TI Interactions of Prototype Foamy Virus Capsids with Host Cell Polo-Like Kinases Are Important for Efficient Viral DNA Integration SO PLOS PATHOGENS LA English DT Article ID CORE PROTEIN; HIV-1 INFECTION; RETROVIRAL INTEGRATION; REVERSE TRANSCRIPTION; NUCLEAR-LOCALIZATION; BOX DOMAIN; IN-VIVO; GAG; PLK1; PHOSPHORYLATION AB Unlike for other retroviruses, only a few host cell factors that aid the replication of foamy viruses (FVs) via interaction with viral structural components are known. Using a yeast-two-hybrid (Y2H) screen with prototype FV (PFV) Gag protein as bait we identified human polo-like kinase 2 (hPLK2), a member of cell cycle regulatory kinases, as a new interactor of PFV capsids. Further Y2H studies confirmed interaction of PFV Gag with several PLKs of both human and rat origin. A consensus Ser-Thr/Ser-Pro (S-T/S-P) motif in Gag, which is conserved among primate FVs and phosphorylated in PFV virions, was essential for recognition by PLKs. In the case of rat PLK2, functional kinase and polo-box domains were required for interaction with PFV Gag. Fluorescently-tagged PFV Gag, through its chromatin tethering function, selectively relocalized ectopically expressed eGFP-tagged PLK proteins to mitotic chromosomes in a Gag STP motif-dependent manner, confirming a specific and dominant nature of the Gag-PLK interaction in mammalian cells. The functional relevance of the Gag-PLK interaction was examined in the context of replication-competent FVs and single-round PFV vectors. Although STP motif mutated viruses displayed wild type (wt) particle release, RNA packaging and intra-particle reverse transcription, their replication capacity was decreased 3-fold in single-cycle infections, and up to 20-fold in spreading infections over an extended time period. Strikingly similar defects were observed when cells infected with single-round wt Gag PFV vectors were treated with a pan PLK inhibitor. Analysis of entry kinetics of the mutant viruses indicated a post-fusion defect resulting in delayed and reduced integration, which was accompanied with an enhanced preference to integrate into heterochromatin. We conclude that interaction between PFV Gag and cellular PLK proteins is important for early replication steps of PFV within host cells. C1 [Zurnic, Irena; Huetter, Sylvia; Rzeha, Ute; Stanke, Nicole; Reh, Juliane; Muellers, Erik; Hamann, Martin V.; Kern, Tobias; Gerresheim, Gesche K.; Lindel, Fabian; Lindemann, Dirk] Tech Univ Dresden, Inst Virol, Med Fac Carl Gustav Carus, Dresden, Germany. [Zurnic, Irena; Huetter, Sylvia; Rzeha, Ute; Stanke, Nicole; Reh, Juliane; Muellers, Erik; Hamann, Martin V.; Kern, Tobias; Gerresheim, Gesche K.; Lindel, Fabian; Lindemann, Dirk] Tech Univ Dresden, CRTD DFG Ctr Regenerat Therapies Dresden, Dresden, Germany. [Serrao, Erik; Engelman, Alan N.] Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA. [Lesbats, Paul; Cherepanov, Peter] Francis Crick Inst, Clare Hall Labs, S Mimms, Herts, England. [Rzeha, Ute] Univ Potsdam, Messeserv, Potsdam, Germany. [Rzeha, Ute] Univ Potsdam, Technol Transfer, NutriAct Innovat Off, Potsdam, Germany. [Muellers, Erik] AstraZeneca R&D Gothenburg, Discovery Sci, Molndal, Sweden. [Kern, Tobias] Tech Univ Dresden, Inst Microbiol, Dresden, Germany. [Gerresheim, Gesche K.] Univ Giessen, Inst Biochem, Fac Med, Giessen, Germany. RP Lindemann, D (reprint author), Tech Univ Dresden, Inst Virol, Med Fac Carl Gustav Carus, Dresden, Germany.; Lindemann, D (reprint author), Tech Univ Dresden, CRTD DFG Ctr Regenerat Therapies Dresden, Dresden, Germany. EM dirk.lindemann@tu-dresden.de RI Cherepanov, Peter/F-6859-2010; OI Cherepanov, Peter/0000-0002-0634-538X; Mullers, Erik/0000-0002-2176-3248 FU DIGS-BB fellowship; Deutsche Forschungsgemeinschaft [Li621/3-3, Li621/4-1, Li621/4-2, Li621/6-1]; US National Institutes of Health [R01 AI052014, P30 AI060354] FX IZ, EM and MVH were partially supported by a DIGS-BB fellowship (https://tu-dresden.de/exzellenz/graduiertenschule/digsbb). This work was partially supported by grants from the Deutsche Forschungsgemeinschaft (http://www.dfg.de/en/index.jsp) (Li621/3-3, Li621/4-1, Li621/4-2, Li621/6-1) to DL and from the US National Institutes of Health (R01 AI052014 to ANE; P30 AI060354 to Harvard University Center for AIDS Research). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 83 TC 1 Z9 1 U1 1 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD AUG PY 2016 VL 12 IS 8 AR e1005860 DI 10.1371/journal.ppat.1005860 PG 36 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA DW1AV UT WOS:000383376000062 PM 27579920 ER PT J AU Stern, TA AF Stern, Theodore A. TI Catastrophic Complications Related to Psychopharmacologic Practice SO PSYCHIATRIC ANNALS LA English DT Editorial Material C1 [Stern, Theodore A.] Harvard Med Sch, Psychiat Field Psychosomat Med Consultat, Boston, MA USA. [Stern, Theodore A.] Massachusetts Gen Hosp, Avery D Weisman Psychiat Consultat Serv, Boston, MA 02114 USA. [Stern, Theodore A.] Massachusetts Gen Hosp, Off Clin Careers, Boston, MA 02114 USA. RP Stern, TA (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Warren Bldg,Room 605, Boston, MA 02114 USA. EM TStern@Partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 EI 1938-2456 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD AUG PY 2016 VL 46 IS 8 BP 436 EP 437 DI 10.3928/00485713-20160721-03 PG 2 WC Psychiatry SC Psychiatry GA DY3VI UT WOS:000385023000003 ER PT J AU Carlo, AD Alpert, JE AF Carlo, Andrew D. Alpert, Jonathan E. TI Catastrophic Drug-Drug Interactions in Psychopharmacology SO PSYCHIATRIC ANNALS LA English DT Article DE m ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; MONOAMINE-OXIDASE INHIBITORS; TORSADE-DE-POINTES; TRICYCLIC ANTIDEPRESSANTS; PSYCHOTROPIC-DRUGS; SEROTONIN TOXICITY; QTC PROLONGATION; CLOMIPRAMINE; INTERVAL; CRITERIA AB Drug interactions may reflect pharmacokinetic processes, pharmacodynamic processes, or both. Some interactions are classified as idiosyncratic, as their mechanisms are not yet understood. Drug inter-actions involving psychotropic medications are ubiquitous; they typically result in changes in drug levels and/or drug effects. Fortunately, most drug interactions in psychiatry do not result in serious harm. Some drug interactions, however, are potentially catastrophic. The focus of this review is on the principal mechanisms of drug interactions and on potentially serious and life-threatening adverse consequences (eg, serotonin syndrome, hypertensive crises, arrhythmias, anticholinergic toxicity, seizures, dermatologic emergencies, bleeding, respiratory depression) of drug interactions in psychiatry. Patients with refractory psychiatric disorders, as well as medical comorbidity, often require treatment with complex drug regimens. The risk of catastrophic drug interactions involving psychotropic medications may be minimized by knowledge of the mechanisms of drug interactions and by familiarity with the rare, yet potentially life-threatening drug interactions that involve psychotropic medications. C1 [Carlo, Andrew D.] Massachusetts Gen Hosp, McLean Hosp, Adult Psychiat Residency Program, Boston, MA 02114 USA. [Carlo, Andrew D.] Harvard Med School, Psychiat, Boston, MA USA. [Alpert, Jonathan E.] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. [Alpert, Jonathan E.] Massachusetts Gen Hosp, Depress Clin & Res Program, Dept Psychiat, Boston, MA 02114 USA. RP Carlo, AD (reprint author), Massachusetts Gen Hosp, WACC 812, 15 Parkman St, Boston, MA 02114 USA. EM acarlo@partners.org FU Luye Pharmaceuticals FX Jonathan E. Alpert discloses consultant fees from Luye Pharmaceuticals and a royalty from Belvoir Publications Inc. The remaining author has no relevant financial relationships to disclose. NR 30 TC 0 Z9 0 U1 3 U2 3 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 EI 1938-2456 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD AUG PY 2016 VL 46 IS 8 BP 439 EP 447 DI 10.3928/00485713-20160623-01 PG 9 WC Psychiatry SC Psychiatry GA DY3VI UT WOS:000385023000004 ER PT J AU Carlo, AD Alpert, JE AF Carlo, Andrew D. Alpert, Jonathan E. TI Clinically Relevant Complications of Drug-Food Interactions in Psychopharmacology SO PSYCHIATRIC ANNALS LA English DT Article ID LEVOTHYROXINE; METABOLISM; ABSORPTION; LURASIDONE; THERAPY; DIET AB Although often overlooked, the interaction of psychotropic medications with food or dietary health supplements can be clinically relevant, and in some cases it may be catastrophic. In this review, we highlight clinically significant drug-food interactions in psychiatry, including those related to hypertensive crises with mono amine oxidase inhibitors, absorption of medications (such as levothyroxine, ziprasidone, and lurasidone), coadministration with food, the excretion of lithium and other medications in the setting of dietary changes, and the impact of grapefruit juice, St. John's wort, cruciferous vegetables, charbroiled meats, dietary supplements, and alcohol on drug metabolism, Routine inquiry about dietary habits and use of dietary supplements as well as enhanced anticipation and monitoring for potential drug-food interactions is an integral component of optimal psychopharmacologic practice. C1 [Carlo, Andrew D.] Massachusetts Gen Hosp, McLean Hosp, Adult Psychiat Residency Program, Boston, MA 02114 USA. [Carlo, Andrew D.] Harvard Med Sch, Psychiat, Boston, MA USA. [Alpert, Jonathan E.] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. [Alpert, Jonathan E.] Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. RP Carlo, AD (reprint author), Massachusetts Gen Hosp, WACC 812, 15 Parkman St, Boston, MA 02114 USA. EM acorlo@portners.org FU Luye Pharmaceuticals FX Jonathan E. Alpert discloses consultant fees from Luye Pharmaceuticals and a royalty from Belvoir Publications Inc. The remaining author has no relevant financial relationships to disclose. NR 25 TC 0 Z9 0 U1 2 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 EI 1938-2456 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD AUG PY 2016 VL 46 IS 8 BP 448 EP 455 DI 10.3928/00485713-20160613-01 PG 8 WC Psychiatry SC Psychiatry GA DY3VI UT WOS:000385023000005 ER PT J AU Stevens, JR Rodgers, JJ Stern, TA AF Stevens, Jonathan R. Rodgers, Joshua J. Stern, Theodore A. TI Idiosyncratic Adverse Reactions to Psychotropic Medications SO PSYCHIATRIC ANNALS LA English DT Article ID NEUROLEPTIC MALIGNANT SYNDROME; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; RANDOMIZED CONTROLLED-TRIAL; TOXIC EPIDERMAL NECROLYSIS; STEVENS-JOHNSON SYNDROME; INDUCED LIVER-INJURY; ANTIEPILEPTIC DRUGS; LITHIUM; CHILDREN; PRIAPISM AB Idiosyncratic adverse events related to psychotropic medications are prevalent and problematic, and they are the most frequent cause of postmarketing (or black-box) warnings and withdrawals of drugs from the market. This review examines the clinical nature of idiosyncratic adverse events, predictors of their onset, and the role of clinician awareness in avoiding irreversible and serious injury from medications prescribed for psychiatric conditions. Idiosyncratic reactions can be minimized or avoided by knowledge of risk factors, cautious use (or avoidance) of specific agents in subpopulations at risk, informed dose titration, and careful monitoring of clinical response. C1 [Stevens, Jonathan R.] Menninger Clin, Outpatient Serv, Houston, TX USA. [Stevens, Jonathan R.; Rodgers, Joshua J.] Baylor Coll Med, Psychiat & Behav Sci, Houston, TX 77030 USA. [Rodgers, Joshua J.] Menninger Clin, 12301 Main St, Houston, TX 77035 USA. [Stern, Theodore A.] Massachusetts Gen Hosp, Psychiat Consultat Serv, Boston, MA 02114 USA. RP Stevens, JR (reprint author), Menninger Clin, 12301 Main St, Houston, TX 77035 USA. EM jonstevens@menninger.edu FU Academy of Psychosomatic Medicine FX Theodore A. Stern receives a salary for his work as Editor-in-Chief of the journal Psychosomatics (Academy of Psychosomatic Medicine), has received royalties from Elsevier for his role as Editor of Massachusetts General Hospital Comprehensive Clinical Psychiatry, and for his role as Editor of Massachusetts General Hospital Psychiatry Update and Board Preparation. The remaining authors have no relevant financial relationships to disclose. NR 65 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 EI 1938-2456 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD AUG PY 2016 VL 46 IS 8 BP 456 EP 465 DI 10.3928/00485713-20160622-01 PG 10 WC Psychiatry SC Psychiatry GA DY3VI UT WOS:000385023000006 ER PT J AU Jenkins, J Glass, S AF Jenkins, James Glass, Sean TI Catastrophic Complications Related to Psychopharmacologic Drug Withdrawal SO PSYCHIATRIC ANNALS LA English DT Article ID ANTIDEPRESSANT DISCONTINUATION SYNDROME; SUPERSENSITIVITY PSYCHOSIS; ATYPICAL ANTIPSYCHOTICS; DIAGNOSTIC-CRITERIA; SYMPTOMS; BENZODIAZEPINES; RECOMMENDATIONS; DETOXIFICATION; MANAGEMENT; DISORDER AB Numerous physical and psychiatric effects can be attributed to the cessation of psychotropic medications, similar to those agents with abuse potential. In addition, drug withdrawal can exacerbate underlying psychiatric conditions and alter disease course and long-term outcomes. This article discusses specific withdrawal syndromes associated with several classes of psychotropic medications to increase prescriber awareness when tapering and discontinuing psychotropic medications, thereby facilitating discussions with patients about the risks of withdrawal. C1 [Jenkins, James] Massachusetts Gen Hosp, McLean Hosp, Adult Psychiat Residency Program, Boston, MA 02114 USA. [Jenkins, James; Glass, Sean] Harvard Med Sch, Psychiat, Boston, MA USA. [Glass, Sean] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jenkins, J (reprint author), Mailstop 109,115 Mill St, Belmont, MA 02478 USA. EM jajenkins@partners.org NR 32 TC 0 Z9 0 U1 1 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 EI 1938-2456 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD AUG PY 2016 VL 46 IS 8 BP 466 EP 472 DI 10.3928/00485713-20160621-01 PG 7 WC Psychiatry SC Psychiatry GA DY3VI UT WOS:000385023000007 ER PT J AU Pasqualucci, L Zhang, BC AF Pasqualucci, Laura Zhang, Baochun TI Genetic drivers of NF-kappa B deregulation in diffuse large B-cell lymphoma SO SEMINARS IN CANCER BIOLOGY LA English DT Review DE DLBCL; Germinal center; NF-kappa B; Genetic lesions ID GERMINAL-CENTER; ACTIVATION; SURVIVAL; IMMUNOGLOBULIN; LYMPHOCYTES; EXPRESSION; DYNAMICS; CENTERS; PROLIFERATION; INACTIVATION AB Diffuse large B cell lymphoma (DLBCL) is the most common form of B cell non-Hodgkin lymphoma worldwide and comprises a heterogeneous group of malignancies that originate from the malignant transformation of germinal center (GC) B cells. Over the past decade, significant improvement has been achieved in our understanding of the molecular pathogenesis underlying this disease, thanks in part to the implementation of powerful genomic technologies allowing genome-wide structural and functional analyses. These studies revealed the presence of multiple oncogenic alterations dysregulating signal transduction pathways that are normally required for the normal biology of the cells from which these tumors are derived. Among the pathways identified as recurrent targets of genetic lesions in DLBCL, NF-kappa B has emerged as a central player in the development and maintenance of this disease, particularly in the less curable, activated B cell (ABC)-like subtype. These lesions reveal vulnerabilities of the lymphoma cells that can be exploited for the design of more rationale therapeutic approaches. The purpose of this review is to summarize recent progresses in understanding the role of NF-kappa B deregulation in the pathogenesis of DLBCL, with emphasis on the genetic basis underlying its aberrant activation, in relationship to the normal biology of B lymphocytes, and the modelling of these lesions in the mouse. (C) 2016 Published by Elsevier Ltd. C1 [Pasqualucci, Laura] Columbia Univ, Inst Canc Genet, Dept Pathol & Cell Biol, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA. [Zhang, Baochun] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Pasqualucci, L (reprint author), Columbia Univ, Inst Canc Genet, Dept Pathol & Cell Biol, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA. EM lp171@columbia.edu FU American Society of Hematology Scholar Award; [R01CA172492-02] FX Supported in part by Grant R01CA172492-02 (to L.P.) and an American Society of Hematology Scholar Award (to B. Z.). NR 54 TC 1 Z9 1 U1 1 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD AUG PY 2016 VL 39 BP 26 EP 31 DI 10.1016/j.semcancer.2016.08.001 PG 6 WC Oncology SC Oncology GA DY1NY UT WOS:000384862900004 PM 27546290 ER PT J AU Matthews, GM Simoes, RD Dhimolea, E Sheffer, M Gandolfi, S Dashevsky, O Sorrell, JD Mitsiades, CS AF Matthews, Geoffrey M. Simoes, Ricardo de Matos Dhimolea, Eugen Sheffer, Michal Gandolfi, Sara Dashevsky, Olga Sorrell, Jeffrey D. Mitsiades, Constantine S. TI NF-kappa B dysregulation in multiple myeloma SO SEMINARS IN CANCER BIOLOGY LA English DT Review DE Myeloma; NF-kappaB; Microenvironment; Stromal cells; Proteasome inhibitors ID PROTEASOME INHIBITOR BORTEZOMIB; PANOBINOSTAT PLUS BORTEZOMIB; CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKINS-LYMPHOMA; MARROW STROMAL CELLS; SUPPRESSOR-CELLS; BREAST-CANCER; PHASE-II; HEMATOLOGIC MALIGNANCIES; COMBINATION THERAPY AB The nuclear factor-kappa B (NF-kappa B) transcription factor family plays critical roles in the pathophysiology of hematologic neoplasias, including multiple myeloma. The current review examines the roles that this transcription factor system plays in multiple myeloma cells and the nonmalignant accessory cells of the local microenvironment; as well as the evidence indicating that a large proportion of myeloma patients harbor genomic lesions which perturb diverse genes regulating the activity of NF-kappa B. This article also discusses the therapeutic targeting of the NF-kappa B pathway using proteasome inhibitors, a pharmacological class that has become a cornerstone in the therapeutic management of myeloma; and reviews some of the future challenges and opportunities for NF-kappa B-related research in myeloma. (C) 2016 Published by Elsevier Ltd. C1 [Matthews, Geoffrey M.; Simoes, Ricardo de Matos; Dhimolea, Eugen; Sheffer, Michal; Gandolfi, Sara; Dashevsky, Olga; Sorrell, Jeffrey D.; Mitsiades, Constantine S.] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. RP Mitsiades, CS (reprint author), Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Dept Med, 450 Brookline Ave,Harvard Inst Med Bldg, Boston, MA 02215 USA. EM Constantine_Mitsiades@dfci.harvard.edu FU National Institutes of Health [R01 CA127435, R01 CA179483, R01 CA196664]; Shawna Ashlee Corman Investigatorship in Multiple Myeloma Research; de Gunzburg Myeloma Research Fund; Cobb Family Myeloma Research Fund; Chambers Family Advanced Myeloma Research Fund; Leukemia and Lymphoma Society; Multiple Myeloma Research Foundation; RJ Corman Multiple Myeloma Research Fund; Claudia Adams Barr Program in Cancer Research; American Australian Association; International Myeloma Foundation; Human Frontier Science Program FX The research studies of CSM have been supported by Grants R01 CA127435, R01 CA179483 and R01 CA196664 from the National Institutes of Health, the Shawna Ashlee Corman Investigatorship in Multiple Myeloma Research, the de Gunzburg Myeloma Research Fund, the Cobb Family Myeloma Research Fund, the Chambers Family Advanced Myeloma Research Fund, the Leukemia and Lymphoma Society Translational Research Program and Quest for Cure Program, the Multiple Myeloma Research Foundation and the RJ Corman Multiple Myeloma Research Fund. CSM and ED are also supported by the Claudia Adams Barr Program in Cancer Research. GMM has been supported by the American Australian Association and the International Myeloma Foundation. MS is supported by the Human Frontier Science Program. NR 144 TC 1 Z9 1 U1 4 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD AUG PY 2016 VL 39 BP 68 EP 76 DI 10.1016/j.semcancer.2016.08.005 PG 9 WC Oncology SC Oncology GA DY1NY UT WOS:000384862900009 PM 27544796 ER PT J AU Yeboah, A Cohen, RI Rabolli, C Yarmush, ML Berthiaume, F AF Yeboah, Agnes Cohen, Rick I. Rabolli, Charles Yarmush, Martin L. Berthiaume, Francois TI Elastin-Like Polypeptides: A Strategic Fusion Partner for Biologics SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Review DE elastin-like peptides (ELP); ELPylation; biologics; biopharmaceutical; purification ID AFFINITY PRECIPITATION; RECOMBINANT PROTEINS; ELP-Z; ESCHERICHIA-COLI; MONOCLONAL-ANTIBODY; TRANSGENIC PLANTS; PURIFICATION; EXPRESSION; PEPTIDES; TOBACCO AB Elastin-like peptides (ELPs) are derivatives of tropoelastin with a unique property that allows them to stay soluble below a certain critical temperature but reversibly form aggregates above that temperature. Since they are derived from tropoelastin, ELPs are biocompatible, non-toxic, and non-immunogenic. The unique properties of ELPs have made them a desirable class of fusion tags used in several biomedical applications including targeted drug delivery and enhancing the half-life of protein drugs. The most significant property of an ELP is that when fused to other proteins, the phase transition property of the ELP is maintained, and the target protein can be purified using the thermally driven property of the ELP. The ELP tag purification process is simple and inexpensive, and involves cycling the protein above and below the transition temperature of the ELP fusion followed by centrifugation to obtain the desired protein, without any need for chromatography. Consequently, using ELPs as a purification tag should be potentially interesting to biopharmaceutical companies who spend a significant percentage of their manufacturing costs on expensive protein purification techniques such as chromatography and filtration. However, ELP tags have not yet been used for commercial protein purification due to some challenges of translating this technique, which has been demonstrated mostly in academic laboratories, to a biotechnology manufacturing environment. The article first reviews the state-of-the-art in protein "ELPylation," and discusses some applications which have benefitted from using ELP as a fusion tag. Then, the article discusses the main advantages of using ELP as a purification tag, and evaluates the remaining hurdles for its implementation in industrial protein production. (C) 2016 Wiley Periodicals, Inc. C1 [Yeboah, Agnes] Rutgers State Univ, Dept Chem & Biochem Engn, Piscataway, NJ USA. [Cohen, Rick I.; Rabolli, Charles; Yarmush, Martin L.; Berthiaume, Francois] Rutgers State Univ, Dept Biomed Engn, 599 Taylor Rd, Piscataway, NJ 08854 USA. [Yarmush, Martin L.] Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. [Yarmush, Martin L.] Shriners Burns Hosp, Boston, MA USA. RP Berthiaume, F (reprint author), Rutgers State Univ, Dept Biomed Engn, 599 Taylor Rd, Piscataway, NJ 08854 USA. EM fberthia@rci.rutgers.edu FU Shriners Hospitals for Children; New Jersey Commission for Spinal Cord Research FX Contract grant sponsor: Shriners Hospitals for Children; Contract grant sponsor: New Jersey Commission for Spinal Cord Research NR 68 TC 0 Z9 1 U1 13 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-3592 EI 1097-0290 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD AUG PY 2016 VL 113 IS 8 BP 1617 EP 1627 DI 10.1002/bit.25998 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA DX9XU UT WOS:000384751100001 PM 27111242 ER PT J AU Xicola, RM Bontu, S Doyle, BJ Rawson, J Garre, P Lee, E de la Hoya, M Bessa, X Clofent, J Bujanda, L Balaguer, F Castellvi-Bel, S Alenda, C Jover, R Ruiz-Ponte, C Syngal, S Andreu, M Carracedo, A Castells, A Newcomb, PA Lindor, N Potter, JD Baron, JA Ellis, NA Caldes, T LLor, X AF Xicola, Rosa M. Bontu, Sneha Doyle, Brian J. Rawson, Jamie Garre, Pilar Lee, Esther de la Hoya, Miguel Bessa, Xavier Clofent, Joan Bujanda, Luis Balaguer, Francesc Castellvi-Bel, Sergi Alenda, Cristina Jover, Rodrigo Ruiz-Ponte, Clara Syngal, Sapna Andreu, Montserrat Carracedo, Angel Castells, Antoni Newcomb, Polly A. Lindor, Noralane Potter, John D. Baron, John A. Ellis, Nathan A. Caldes, Trinidad LLor, Xavier TI Association of a let-7 miRNA binding region of TGFBR1 with hereditary mismatch repair proficient colorectal cancer (MSS HNPCC) SO CARCINOGENESIS LA English DT Article ID WIDE LINKAGE SCAN; COLON-CANCER; SUSCEPTIBILITY; RISK; VARIANTS; CRITERIA; TGFBR1-ASTERISK-6A; PREDISPOSITION; POLYMORPHISMS; PROGRESSION AB We describe an association between TGFBR1 polymorphism rs868 and mismatch repair proficient hereditary colorectal cancers. This polymorphism results in more binding of TGFBR1 to let-7b-5p miRNA, which would result in lower expression of TGFBR1 and thus higher colorectal cancer risk.The purpose of this study was to identify novel colorectal cancer (CRC)-causing alleles in unexplained familial CRC cases. In order to do so, coding regions in five candidate genes (MGMT, AXIN2, CTNNB1, TGFBR1 and TGFBR2) were sequenced in 11 unrelated microsatellite-stable hereditary non-polyposis CRC (MSS HNPCC) cases. Selected genetic variants were genotyped in a discovery set of 27 MSS HNPCC cases and 85 controls. One genetic variant, rs67687202, in TGFBR1 emerged as significant (P = 0.002), and it was genotyped in a replication set of 87 additional MSS HNPCC-like cases and 338 controls where it was also significantly associated with MSS HNPCC cases (P = 0.041). In the combined genotype data, rs67687202 was associated with a moderate increase in CRC risk (OR = 1.68; 95% CI = 1.13-2.50; P = 0.010). We tested a highly correlated SNP rs868 in 723 non-familial CRC cases compared with 629 controls, and it was not significantly associated with CRC risk (P = 0.370). rs868 is contained in a let-7 miRNA binding site in the 3'UTR of TGFBR1, which might provide a functional basis for the association in MSS HNPCC. In luciferase assays, the risk-associated allele for rs868 was associated with half the luciferase expression in the presence of miRNA let-7b-5p compared with protective allele, suggesting more binding of let-7b-5p and less TGFBR1 expression. Thus, rs868 potentially is a CRC risk-causing allele. Our results support the concept that rs868 is associated with lower TGFBR1 expression thereby increasing CRC risk. C1 [Xicola, Rosa M.; Bontu, Sneha; LLor, Xavier] Yale Univ, Dept Med, New Haven, CT 06520 USA. [Xicola, Rosa M.; Bontu, Sneha; LLor, Xavier] Yale Univ, Ctr Canc, New Haven, CT 06520 USA. [Doyle, Brian J.; Rawson, Jamie; Lee, Esther] Univ Illinois, Dept Med, Chicago, IL USA. [Doyle, Brian J.; Rawson, Jamie; Lee, Esther] Univ Illinois, Ctr Canc, Chicago, IL USA. [Garre, Pilar; de la Hoya, Miguel; Caldes, Trinidad] Hosp Clin San Carlos, IdISSC, Lab Oncol Mol, Madrid, Spain. [Bessa, Xavier; Andreu, Montserrat] Hosp del Mar, Dept Gastroenterol, Barcelona, Catalonia, Spain. [Clofent, Joan] Hosp Sagunto, Dept Gastroenterol, Valencia, Spain. [Bujanda, Luis] Univ Pais Vasco UPV EHU, Hosp Donostia, Inst Biodonostia, Dept Gastroenterol,CIBERehd, San Sebastian, Spain. [Balaguer, Francesc; Castellvi-Bel, Sergi; Castells, Antoni] Univ Barcelona, Hosp Clin, Dept Gastroenterol, IDIBAPS,CIBERehd, Barcelona, Spain. [Alenda, Cristina; Jover, Rodrigo] Hosp Gen Univ Alicante, Dept Gastroenterol, Alicante, Spain. [Alenda, Cristina; Jover, Rodrigo] Hosp Gen Univ Alicante, Dept Pathol, Alicante, Spain. [Ruiz-Ponte, Clara; Carracedo, Angel] FPGMX, SERGAS, Ctr Invest Biomed Red Enfermedades Raras CIBERer, Grp Med Xen,IDIS, Santiago De Compostela, Galiza, Spain. [Syngal, Sapna] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Lindor, Noralane] Mayo Clin, Dept Hlth Sci Res, Scottsdale, AZ USA. [Potter, John D.] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, 1124 Columbia St, Seattle, WA 98104 USA. [Potter, John D.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Potter, John D.] Ctr Publ Hlth Res, Wellington, New Zealand. [Baron, John A.] Dartmouth Coll, Dept Biostat & Epidemiol, 1 Med Ctr Dr, Lebanon, NH 03756 USA. [Ellis, Nathan A.] Univ Arizona, Dept Cellular & Mol Med, Tucson, AZ USA. RP LLor, X (reprint author), Yale Univ, Dept Med, New Haven, CT 06520 USA.; LLor, X (reprint author), Yale Univ, Ctr Canc, New Haven, CT 06520 USA.; Caldes, T (reprint author), Hosp Clin San Carlos, IdISSC, Lab Oncol Mol, Madrid, Spain. EM trinidad.caldes@salud.madrid.org; xavier.llor@yale.edu OI Bessa Caserras, Xavier/0000-0003-4680-1228 FU Sirazi Foundation; University of Illinois at Chicago, Office of the Vice Chancellor for Research; Department of Medicine and Cancer Center of the University of Illinois; ISCIII (Spain) [PI13/02588, RD12/0036/006]; European Regional Development FEDER funds; National Cancer Institute [UM1 CA167551] FX This work was supported in part by Sirazi Foundation; Area of Excellence Award from the University of Illinois at Chicago, Office of the Vice Chancellor for Research; the Department of Medicine and Cancer Center of the University of Illinois (X.L.). T.C., P.G. and M.d.H. were supported by PI13/02588 and RD12/0036/006 from ISCIII (Spain) and the European Regional Development FEDER funds. The Colon Cancer Family Registry (CCFR) was supported by grant UM1 CA167551 from the National Cancer Institute. The following CCFR centers provided samples and data for this study: Australasian Colorectal Cancer Family Registry (U01/U24 CA097735), USC Consortium Colorectal Cancer Family Registry (U01/U24 CA074799), Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01/U24 CA074800), Ontario Registry for Studies of Familial Colorectal Cancer (U01/U24 CA074783), Seattle Colorectal Cancer Family Registry (U01/U24 CA074794) and University of Hawaii Colorectal Cancer Family Registry (U01/U24 CA074806). NR 50 TC 0 Z9 0 U1 5 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 2016 VL 37 IS 8 BP 751 EP 758 DI 10.1093/carcin/bgw064 PG 8 WC Oncology SC Oncology GA DV8OF UT WOS:000383195600002 PM 27234654 ER PT J AU Lanham, HJ Palmer, RF Leykum, LK McDaniel, RR Nutting, PA Stange, KC Crabtree, BF Miller, WL Jaen, CR AF Lanham, Holly Jordan Palmer, Raymond F. Leykum, Luci K. McDaniel, Reuben R., Jr. Nutting, Paul A. Stange, Kurt C. Crabtree, Benjamin F. Miller, William L. Jaen, Carlos Roberto TI Trust and Reflection in Primary Care Practice Redesign SO HEALTH SERVICES RESEARCH LA English DT Article DE Practice redesign; relationships; reflection; sensemaking; learning ID CENTERED MEDICAL HOME; NATIONAL DEMONSTRATION PROJECT; COMPLEXITY SCIENCE; HEALTH-CARE; TRANSFORMATION; LESSONS; TEAMS; ORGANIZATIONS; SENSEMAKING; SAFETY AB Objective. To test a conceptual model of relationships, reflection, sensemaking, and learning in primary care practices transitioning to patient-centered medical homes (PCMH). Data Sources/Study Setting. Primary data were collected as part of the American Academy of Family Physicians' National Demonstration Project of the PCMH. Study Design. We conducted a cross-sectional survey of clinicians and staff from 36 family medicine practices across the United States. Surveys measured seven characteristics of practice relationships (trust, diversity, mindfulness, heedful interrelation, respectful interaction, social/task relatedness, and rich and lean communication) and three organizational attributes (reflection, sensemaking, and learning) of practices. Data Collection/Extraction Methods. We surveyed 396 clinicians and practice staff. We performed a multigroup path analysis of the data. Parameter estimates were calculated using a Bayesian estimation method. Principal Findings. Trust and reflection were important in explaining the characteristics of practice relationships and their associations with sensemaking and learning. The strongest associations between relationships, sensemaking, and learning were found under conditions of high trust and reflection. The weakest associations were found under conditions of low trust and reflection. Conclusions. Trust and reflection appear to play a key role in moderating relationships, sensemaking, and learning in practices undergoing practice redesign. C1 [Lanham, Holly Jordan; Leykum, Luci K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med Hosp Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. [Lanham, Holly Jordan; Palmer, Raymond F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. [Lanham, Holly Jordan; Leykum, Luci K.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Lanham, Holly Jordan; Leykum, Luci K.; McDaniel, Reuben R., Jr.] Univ Texas Austin, Dept Informat Risk & Operat Management, McCombs Sch Business, San Antonio, TX USA. [Nutting, Paul A.] Ctr Res Strategies, Denver, CO USA. [Stange, Kurt C.] Case Western Reserve Univ, Dept Family Med, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA. [Stange, Kurt C.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA. [Stange, Kurt C.] Case Western Reserve Univ, Dept Sociol, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA. [Crabtree, Benjamin F.] Rutgers Robert Wood Johnson Med Sch, Dept Family Med & Community Hlth, New Brunswick, NJ USA. [Miller, William L.] Lehigh Valley Hlth Network, Dept Family Med, Allentown, PA USA. [Jaen, Carlos Roberto] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, Res Adv Community Hlth Ctr, San Antonio, TX 78229 USA. [Jaen, Carlos Roberto] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, Res Adv Community Hlth Ctr, San Antonio, TX 78229 USA. RP Lanham, HJ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med Hosp Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.; Lanham, HJ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.; Lanham, HJ (reprint author), South Texas Vet Hlth Care Syst, San Antonio, TX USA.; Lanham, HJ (reprint author), Univ Texas Austin, Dept Informat Risk & Operat Management, McCombs Sch Business, San Antonio, TX USA. EM lanham@uthscsa.edu FU American Academy of Family Physicians; Commonwealth Fund, a national, private foundation based in New York City; Department of Veterans Affairs; Veterans Health Administration; Health Services Research and Development Service [CDA 07-022]; South Texas Veterans Health Care System; Charles and Elizabeth Prothro Chair in Health Care Management, the University of Texas at Austin; Harry and Elsa Jiler American Cancer Society; National Cancer Institute [K05 CA140237] FX The authors express their appreciation for the cooperation and dedication of the physicians and staff of the family practices that participated in the NDP. We also thank the anonymous reviewers for their comments and insights. The American Academy of Family Physicians provided funding support for this evaluation, including a Research Center grant. The evaluation was also partially supported by the Commonwealth Fund, a national, private foundation based in New York City that supports independent research on health care issues and makes grants to improve health care practice and policy. LKL was supported by the Department of Veterans Affairs, Veterans Health Administration, and Health Services Research and Development Service (CDA 07-022) and her investigator salary support is provided through this funding and through the South Texas Veterans Health Care System. RMD receives support from the Charles and Elizabeth Prothro Chair in Health Care Management, the University of Texas at Austin. KCS was supported in part by the Harry and Elsa Jiler American Cancer Society Clinical Research Professorship. BFC was supported in part by a National Cancer Institute K05 Senior Investigator Award (K05 CA140237). NR 72 TC 1 Z9 1 U1 6 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 EI 1475-6773 J9 HEALTH SERV RES JI Health Serv. Res. PD AUG PY 2016 VL 51 IS 4 BP 1489 EP 1514 DI 10.1111/1475-6773.12415 PG 26 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA DX9VO UT WOS:000384745300010 PM 26611650 ER PT J AU Keating, NL Kouri, EM He, YL Freedman, RA Volya, R Zaslavsky, AM AF Keating, Nancy L. Kouri, Elena M. He, Yulei Freedman, Rachel A. Volya, Rita Zaslavsky, Alan M. TI Location Isn't Everything: Proximity, Hospital Characteristics, Choice of Hospital, and Disparities for Breast Cancer Surgery Patients SO HEALTH SERVICES RESEARCH LA English DT Article DE Breast cancer; surgery; health care disparities; hospital racial composition; distance ID ACUTE MYOCARDIAL-INFARCTION; SEER-MEDICARE DATA; QUALITY-OF-CARE; HEALTH-CARE; BLACK PATIENTS; RACIAL DISPARITIES; UNDERGO-SURGERY; UNITED-STATES; SATISFACTION; CONCORDANCE AB Objective. Assess the relative importance of proximity and other hospital characteristics in the choice of hospital for breast cancer surgery by race/ethnicity. Data. SEER-Medicare data. Study Design. Observational study of women aged >65 years receiving surgery for stage I/II/III breast cancer diagnosed in 1992-2007 in Detroit (N = 10,746 white/black), Atlanta (N = 4,018 white/black), Los Angeles (N = 9,433 white/black/Asian/Hispanic), and San Francisco (N = 4,856 white/black/Asian). We calculated the distance from each patient's census tract of residence to each area hospital. We estimated discrete choice models for the probability of receiving surgery at each hospital based on distance and assessed whether deviations from these predictions entailed interactions of hospital characteristics with the patient's race/ethnicity. We identified high-quality hospitals by rates of adjuvant radiation therapy and by survey measures of patient experiences, and we assessed how observed surgery rates at high-quality hospitals deviated from those predicted based on distance alone. Principal Findings. Proximity was significantly associated with hospital choice in all areas. Minority more often than white breast cancer patients had surgery at hospitals with more minority patients, those treating more Medicaid patients, and in some areas, lower quality hospitals. Conclusions. Residential location alone does not explain concentration of racial/ethnic-minority breast cancer surgery patients in certain hospitals that are sometimes of lower quality. C1 [Keating, Nancy L.; Kouri, Elena M.; Volya, Rita; Zaslavsky, Alan M.] Harvard Med Sch, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, 75 Francis St, Boston, MA 02115 USA. [He, Yulei] Ctr Dis Control & Prevent, Off Res & Methodol, Natl Ctr Hlth Stat, Hyattsville, MD USA. [Freedman, Rachel A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Keating, NL (reprint author), Harvard Med Sch, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA.; Keating, NL (reprint author), Brigham & Womens Hosp, Div Gen Internal Med, 75 Francis St, Boston, MA 02115 USA. EM keating@hcp.med.harvard.edu FU California Department of Public Health as part of the statewide cancer reporting program; National Cancer Institute's Surveillance, Epidemiology and End Results Program [N01-PC-35136, N01-PC-35139, N02-PC-15105]; Centers for Disease Control and Prevention's National Program of Cancer Registries [U55/CCR921930-02]; Susan G. Komen for the Cure FX This study used the linked SEER-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors. The authors acknowledge the efforts of the Applied Research Program, NCI; the Office of Research, Development and Information, CMS; Information Management Services (IMS), Inc.; and the Surveillance, Epidemiology, and End Results (SEER) Program tumor registries in the creation of the SEER-Medicare database. The collection of the California cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute's Surveillance, Epidemiology and End Results Program under contract N01-PC-35136 awarded to the Northern California Cancer Center, contract N01-PC-35139 awarded to the University of Southern California, and contract N02-PC-15105 awarded to the Public Health Institute; and the Centers for Disease Control and Prevention's National Program of Cancer Registries, under agreement #U55/CCR921930-02 awarded to the Public Health Institute. The ideas and opinions expressed herein are those of the author(s) and endorsement by the State of California, Department of Public Health the National Cancer Institute, and the Centers for Disease Control and Prevention or their Contractors and Subcontractors is not intended nor should be inferred. This paper was developed while Yulei He was at Harvard Medical School. The findings and conclusions in this paper are those of the authors and do not necessarily represent the official position of the National Center for Health Statistics, Centers for Disease Control and Prevention. The study was supported by Susan G. Komen for the Cure. NR 28 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 EI 1475-6773 J9 HEALTH SERV RES JI Health Serv. Res. PD AUG PY 2016 VL 51 IS 4 BP 1561 EP 1583 DI 10.1111/1475-6773.12443 PG 23 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA DX9VO UT WOS:000384745300014 PM 26800094 ER PT J AU Keating, NL Landrum, MB Huskamp, HA Kouri, EM Prigerson, HG Schrag, D Maciejewski, PK Hornbrook, MC Haggstrom, DA AF Keating, Nancy L. Landrum, Mary Beth Huskamp, Haiden A. Kouri, Elena M. Prigerson, Holly G. Schrag, Deborah Maciejewski, Paul K. Hornbrook, Mark C. Haggstrom, David A. TI Dartmouth Atlas Area-Level Estimates of End-of-Life Expenditures: How Well Do They Reflect Expenditures for Prospectively Identified Advanced Lung Cancer Patients? SO HEALTH SERVICES RESEARCH LA English DT Article DE Variation; health care expenditures; lung cancer ID UNITED-STATES; REGIONAL-VARIATIONS; CARE; MEDICARE; OUTCOMES; HOSPITALS; SERVICES; COSTS AB Objective. Assess validity of the retrospective Dartmouth hospital referral region (HRR) end-of-life spending measures by comparing with health care expenditures from diagnosis to death for prospectively identified advanced lung cancer patients. Data/Setting/Design. We calculated health care spending from diagnosis (2003-2005) to death or through 2011 for 885 patients aged >= 65 years with advanced lung cancer using Medicare claims. We assessed the association between Dartmouth HRR-level spending in the last 2 years of life and patient-level spending using linear regression with random HRR effects, adjusting for patient characteristics. Findings. For each $1 increase in the Dartmouth metric, spending for our cohort increased by $0.74 (p < .001). The Dartmouth spending variable explained 93.4 percent of the HRR-level variance in observed spending. Conclusions. HRR-level spending estimates for deceased patient cohorts reflect area-level care intensity for prospectively identified advanced lung cancer patients. C1 [Keating, Nancy L.; Landrum, Mary Beth; Huskamp, Haiden A.; Kouri, Elena M.] Harvard Med Sch, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, 75 Francis St, Boston, MA 02115 USA. [Prigerson, Holly G.] New York Presbyterian Hosp, Ctr Res End Of Life Care, Weill Cornell Med Coll, New York, NY USA. [Schrag, Deborah] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Maciejewski, Paul K.] Weill Cornell Med Coll, Dept Radiol, New York, NY USA. [Hornbrook, Mark C.] Kaiser Permanente Northwest, Ctr Hlth Res, Portland, OR USA. [Haggstrom, David A.] Indiana Univ Sch Med, VA HSR & D Ctr Hlth Informat & Commun, Indianapolis, IN 46202 USA. RP Keating, NL (reprint author), Harvard Med Sch, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA.; Keating, NL (reprint author), Brigham & Womens Hosp, Div Gen Internal Med, 75 Francis St, Boston, MA 02115 USA. EM keating@hcp.med.harvard.edu FU National Cancer Institute [1R01CA164021, K24CA181510, 5U01CA093344-08]; National Cancer Institute (NCI) [U01 CA093344]; NCI [U01 CA093332]; Harvard Medical School/ Northern California Cancer Center [U01 CA093324]; RAND/UCLA [U01 CA093348]; University of Alabama at Birmingham [U01 CA093329]; University of Iowa [U01 CA093339]; University of North Carolina [U01 CA093326]; Department of Veteran's Affairs grant [CRS 02-164] FX This work was funded by 1R01CA164021 from the National Cancer Institute. Dr. Keating is also supported by K24CA181510 from the National Cancer Institute. This original Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium study was supported by grants from the National Cancer Institute (NCI) to the Statistical Coordinating Center (U01 CA093344) and the NCI-supported Primary Data Collection and Research Centers (Dana Farber Cancer Institute/Cancer Research Network U01 CA093332, Harvard Medical School/ Northern California Cancer Center U01 CA093324, RAND/UCLA U01 CA093348, University of Alabama at Birmingham U01 CA093329, University of Iowa U01 CA093339, University of North Carolina U01 CA093326) and by a Department of Veteran's Affairs grant to the Durham VA Medical Center CRS 02-164. The CanCORS II data collection was funded by 5U01CA093344-08 from the National Cancer Institute to the Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium Statistical Coordinating Center. The authors thank Rita Volya, MS, for expert programming assistance. NR 20 TC 1 Z9 1 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 EI 1475-6773 J9 HEALTH SERV RES JI Health Serv. Res. PD AUG PY 2016 VL 51 IS 4 BP 1584 EP 1594 DI 10.1111/1475-6773.12440 PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA DX9VO UT WOS:000384745300015 PM 26799913 ER PT J AU Dekel, S Stanger, V Georgakopoulos, ER Stuebe, CM Dishy, GA AF Dekel, Sharon Stanger, Varda Georgakopoulos, Emily R. Stuebe, Caren M. Dishy, Gabriella A. TI Peripartum Depression, Traditional Culture, and Israeli Society SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE peripartum depression; traditional culture; posttraumatic stress symptoms; ultra-Orthodox; Israel ID POSTTRAUMATIC-STRESS-DISORDER; POSTPARTUM DEPRESSION; RISK-FACTORS; POSTNATAL DEPRESSION; MENTAL-ILLNESS; SYMPTOMS; WOMEN; PREVALENCE; COHORT; ASSOCIATION AB Although it is known that culture affects psychopathology, the nature of the relationship between culture and peripartum depression (PPD) is not fully understood. Here we report on 2 cases of Israeli women who are affiliated with traditional cultural groups that emphasize reproduction but developed PPD after childbirth. The first woman is an ultra-Orthodox Israeli Jew and the second is an Israeli Arab. The 2 cases illustrate the effect of cultural beliefs and rituals on the conceptualization, treatment, and trajectory of PPD. The cases suggest a complex relationship between traditional cultures and PPD, including the possibility that cultural factors may have both adaptive and maladaptive consequences. Future qualitative and quantitative studies are needed to further clarify this relationship. C1 [Dekel, Sharon; Georgakopoulos, Emily R.; Stuebe, Caren M.; Dishy, Gabriella A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dekel, Sharon] Harvard Med Sch, Boston, MA USA. [Stanger, Varda] Sheba Med Ctr, Ramat Gan, Israel. [Stanger, Varda] Bar Ilan Univ, IL-52100 Ramat Gan, Israel. [Georgakopoulos, Emily R.; Stuebe, Caren M.] Boston Univ, Boston, MA 02215 USA. RP Dekel, S (reprint author), Massachusetts Gen Hosp East, PTSD Res Lab, 120 Second Ave, Charlestown, MA 02129 USA. EM sdekel@mgh.harvard.edu FU Claflin Distinguished Scholar Award; Brain and Behavior (NARSAD) grant FX This work was supported by the Claflin Distinguished Scholar Award and the Brain and Behavior (NARSAD) grant awarded to Dr. Dekel. NR 35 TC 0 Z9 0 U1 6 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9762 EI 1097-4679 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD AUG PY 2016 VL 72 IS 8 SI SI BP 784 EP 794 DI 10.1002/jclp.22360 PG 11 WC Psychology, Clinical SC Psychology GA DW4NO UT WOS:000383620200004 PM 27487164 ER PT J AU Karimnejad, K Czerny, MS Lookabaugh, S Lee, DJ Mikulec, AA AF Karimnejad, K. Czerny, M. S. Lookabaugh, S. Lee, D. J. Mikulec, A. A. TI Gender and laterality in semicircular canal dehiscence syndrome SO JOURNAL OF LARYNGOLOGY AND OTOLOGY LA English DT Article DE Semicircular Canals; Vertigo; Hearing Loss; Conductive; Temporal Lobe; Parietal Lobe; Health Status ID VIBRATION-INDUCED NYSTAGMUS; CONDUCTIVE HEARING-LOSS; TULLIO PHENOMENON; CLINICAL-EXPERIENCE; COMPUTED-TOMOGRAPHY; HUMAN BRAIN; CASE SERIES; SUPERIOR; SYMPTOMS; MANAGEMENT AB Objective: To determine if there is gender or laterality predilection in patients with semicircular canal dehiscence syndrome. Methods: A multi-institutional chart review was performed to identify patients diagnosed with semicircular canal dehiscence between 2000 and 2015. A systematic literature search was conducted using PubMed to further identify patients with semicircular canal dehiscence. Age, gender and laterality data were collected. Statistical analysis was performed to evaluate for gender or laterality preponderance. Results: A total of 682 patients with semicircular canal dehiscence were identified by literature and chart review. Mean age of diagnosis was 49.75 years (standard deviation = 15.33). Semicircular canal dehiscence was associated with a statistically significant female predominance (chi-square = 7.185, p = 0.007); the female-to-male ratio was 1.2 to 1. Left-sided semicircular canal dehiscence was most common, followed by right-sided then bilateral (chi-square = 23.457, p < 0.001). Conclusion: Semicircular canal dehiscence syndrome is most commonly left-sided and exhibits a female predominance. This may be secondary to morphological cerebral hemisphere asymmetries in both sexes and a predilection of women to seek more medical care than men. C1 [Karimnejad, K.; Mikulec, A. A.] St Louis Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, 3635 Vista Ave,6FDT, St Louis, MO 63110 USA. [Czerny, M. S.] Ear Nose & Throat Inst Southern Illinois, Swansea, W Glam, Wales. [Lookabaugh, S.] Univ Rochester, Med Ctr, Dept Otolaryngol, New York, NY USA. [Lee, D. J.] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Mikulec, AA (reprint author), St Louis Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, 3635 Vista Ave,6FDT, St Louis, MO 63110 USA. EM mikuleca@slu.edu NR 49 TC 0 Z9 0 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 0022-2151 EI 1748-5460 J9 J LARYNGOL OTOL JI J. Laryngol. Otol. PD AUG PY 2016 VL 130 IS 8 BP 712 EP 716 DI 10.1017/S0022215116008185 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA DX9KQ UT WOS:000384714600004 PM 27345153 ER PT J AU Altawalbeh, SM Thorpe, CT Zgibor, JC Kane-Gill, S Kang, YH Thorpe, JM AF Altawalbeh, Shoroq M. Thorpe, Carolyn T. Zgibor, Janice C. Kane-Gill, Sandra Kang, Yihuang Thorpe, Joshua M. TI Antileukotriene Agents Versus Long-Acting Beta-Agonists in Older Adults with Persistent Asthma: A Comparison of Add-On Therapies SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE asthma; older adults; cardiovascular; Medicare ID INHALED CORTICOSTEROIDS; UNITED-STATES; CONTROLLER MEDICATIONS; CARDIOVASCULAR-DISEASE; RESOURCE UTILIZATION; ELDERLY-PATIENTS; MONTELUKAST; SAFETY; EXACERBATIONS; SURVEILLANCE AB ObjectivesTo compare the effectiveness and cardiovascular safety of long-acting beta-agonists (LABAs) with those of leukotriene receptor antagonists (LTRAs) as add-on treatments in older adults with asthma already taking inhaled corticosteroids (ICSs). DesignRetrospective cohort study. SettingMedicare fee-for-service (FFS) claims (2009-10) for a 10% random sample of beneficiaries continuously enrolled in Parts A, B, and D in 2009. ParticipantsMedicare beneficiaries aged 66 and older continuously enrolled in FFS Medicare with Part D coverage with a diagnosis of asthma before 2009 treated exclusively with ICSs plus LABAs or ICSs plus LTRAs (N = 14,702). MeasurementsThe augmented inverse propensity-weighted estimator was used to compare the effect of LABA add-on therapy with that of LTRA add-on therapy on asthma exacerbations requiring inpatient, emergency, or outpatient care and on cardiovascular (CV) events, adjusting for demographic characteristics, comorbidities, and county-level healthcare-access variables. ResultsThe primary analysis showed that LTRA add-on treatment was associated with greater odds of asthma-related hospitalizations or emergency department visits (odds ratio (OR) = 1.4, P < .001), as well as outpatient exacerbations requiring oral corticosteroids or antibiotics (OR = 1.41, P < .001) than LABA treatment. LTRA add-on therapy was also less effective in controlling acute symptoms, as indicated by greater use of short-acting beta agonists (rate ratio = 1.58, P < .001). LTRA add-on treatment was associated with lower odds of experiencing a CV event than LABA treatment (OR = 0.86, P = .006). ConclusionThis study provides new evidence specific to older adults to help healthcare providers weigh the risks and benefits of these add-on treatments. Further subgroup analysis is needed to personalize asthma treatments in this high-risk population. C1 [Altawalbeh, Shoroq M.] Univ Pittsburgh, Dept Pharmaceut Sci, Ctr Clin Pharmaceut Sci, Pittsburgh, PA USA. [Thorpe, Carolyn T.; Kane-Gill, Sandra; Thorpe, Joshua M.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. [Thorpe, Carolyn T.; Thorpe, Joshua M.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Zgibor, Janice C.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Natl Sun Yat Sen Univ, Dept Informat Management, Kaohsiung, Taiwan. RP Altawalbeh, SM (reprint author), Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, 3501 Terrace St,916 Salk, Pittsburgh, PA 15261 USA. EM sha55@pitt.edu FU University of Pittsburgh School of Pharmacy; Pittsburgh Claude D. Pepper Older Americans Independence Center [NIA P30 AGAG024827] FX The University of Pittsburgh School of Pharmacy and the Pittsburgh Claude D. Pepper Older Americans Independence Center (NIA P30 AGAG024827) provided support for this study. NR 50 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 2016 VL 64 IS 8 BP 1592 EP 1600 DI 10.1111/jgs.14235 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA DW3KW UT WOS:000383541500009 PM 27351988 ER PT J AU Linos, E Chren, MM Cenzer, IS Covinsky, KE AF Linos, Eleni Chren, Mary-Margaret Cenzer, Irena Stijacic Covinsky, Kenneth E. TI Skin Cancer in US Elderly Adults: Does Life Expectancy Play a Role in Treatment Decisions? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE skin cancer; basal cell carcinoma; squamous cell carcinoma; end of life ID BASAL-CELL CARCINOMA; OLDER-ADULTS; VALIDATION; INDEX; CARE; END AB ObjectivesTo examine whether life expectancy influences treatment pattern of nonmelanoma skin cancer, or keratinocyte carcinoma (KC), the most common malignancy and the fifth most costly cancer to Medicare. DesignNationally representative cross-sectional study. SettingNationally representative Health and Retirement Study linked to Medicare claims. ParticipantsTreatments (N = 9,653) from individuals aged 65 and older treated for basal or squamous cell carcinoma between 1992 and 2012 (N = 2,702) were included. MeasurementsLimited life expectancy defined according to aged 85 and older, medical comorbidities, Charlson Comorbidity Index score of 3 or greater, difficulty in at least one activity of daily living (ADL), and a Lee index of 13 or greater. Treatment type (Mohs micrographic surgery (MMS) (most intensive, highest cost), excision, or electrodesiccation and curettage (ED&C) (least intensive, lowest cost)), according to procedure code. ResultsMost KCs (61%) were treated surgically. Rates of MMS (19%), excision (42%), and ED&C (39%) were no different in participants with limited life expectancy and those with normal life expectancy. For example, 19% of participants with difficulty or dependence in ADLs, 20% of those with a Charlson comorbidity score greater than 3, and 15% of those in their last year of life underwent MMS; participants who died within 1 year of diagnosis were treated in the same way as those who lived longer. ConclusionA one-size-fits-all approach in which advanced age, health status, functional status, and prognosis are not associated with intensiveness of treatment appears to guide treatment for KC, a generally nonfatal condition. Although intensive treatment of skin cancer when it causes symptoms may be indicated regardless of life expectancy, persons with limited life expectancy should be given choices to ensure that the treatment matches their goals and preferences. C1 [Linos, Eleni; Chren, Mary-Margaret] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Cenzer, Irena Stijacic; Covinsky, Kenneth E.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA. [Cenzer, Irena Stijacic; Covinsky, Kenneth E.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Linos, E (reprint author), Dept Dermatol, 2340 Sutter St,Room N421 Mail Code Box 0808, San Francisco, CA 94143 USA. EM linose@derm.ucsf.edu FU National Institutes of Health through the National Center for Research Resources [KL2RR024130]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [K24 AR052667, R01 AR 054983]; National Institute of Nursing Research [R01 NR013347]; Claude D. Pepper Older Americans Independence Center at the National Institute on Aging, National Institutes of Health [P30 AG044281] FX This work was supported by the National Institutes of Health through the National Center for Research Resources (Grant KL2RR024130 to EL), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (Grants K24 AR052667 and R01 AR 054983 to MMC), the National Institute of Nursing Research (Grant R01 NR013347 to KC), and the Claude D. Pepper Older Americans Independence Center at the National Institute on Aging, National Institutes of Health (Grant P30 AG044281 to KC). NR 23 TC 0 Z9 0 U1 4 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 2016 VL 64 IS 8 BP 1610 EP 1615 DI 10.1111/jgs.14202 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA DW3KW UT WOS:000383541500011 PM 27303932 ER PT J AU Wallin, JJ Bendell, JC Funke, R Sznol, M Korski, K Jones, S Hernandez, G Mier, J He, X Hodi, FS Denker, M Leveque, V Canamero, M Babitski, G Koeppen, H Ziai, J Sharma, N Gaire, F Chen, DS Waterkamp, D Hegde, PS McDermott, DF AF Wallin, Jeffrey J. Bendell, Johanna C. Funke, Roel Sznol, Mario Korski, Konstanty Jones, Suzanne Hernandez, Genevive Mier, James He, Xian Hodi, F. Stephen Denker, Mitchell Leveque, Vincent Canamero, Marta Babitski, Galina Koeppen, Hartmut Ziai, James Sharma, Neeraj Gaire, Fabien Chen, Daniel S. Waterkamp, Daniel Hegde, Priti S. McDermott, David F. TI Atezolizumab in combination with bevacizumab enhances antigen-specific T-cell migration in metastatic renal cell carcinoma SO NATURE COMMUNICATIONS LA English DT Article ID TUMOR; CANCER; GROWTH; PHASE; ANTIBODY; IDENTIFICATION; VACCINE; TRIAL; MICE AB Anti-tumour immune activation by checkpoint inhibitors leads to durable responses in a variety of cancers, but combination approaches are required to extend this benefit beyond a subset of patients. In preclinical models tumour-derived VEGF limits immune cell activity while anti-VEGF augments intra-tumoral T-cell infiltration, potentially through vascular normalization and endothelial cell activation. This study investigates how VEGF blockade with bevacizumab could potentiate PD-L1 checkpoint inhibition with atezolizumab in mRCC. Tissue collections are before treatment, after bevacizumab and after the addition of atezolizumab. We discover that intra-tumoral CD8(+) T cells increase following combination treatment. A related increase is found in intra-tumoral MHC-I, Th1 and T-effector markers, and chemokines, most notably CX3CL1 (fractalkine). We also discover that the fractalkine receptor increases on peripheral CD8(+) T cells with treatment. Furthermore, trafficking lymphocyte increases are observed in tumors following bevacizumab and combination treatment. These data suggest that the anti-VEGF and anti-PD-L1 combination improves antigen-specific T-cell migration. C1 [Wallin, Jeffrey J.; Funke, Roel; Hernandez, Genevive; He, Xian; Denker, Mitchell; Leveque, Vincent; Koeppen, Hartmut; Ziai, James; Sharma, Neeraj; Chen, Daniel S.; Waterkamp, Daniel; Hegde, Priti S.] Genentech Inc, 1 DNA Way, San Francisco, CA 94080 USA. [Bendell, Johanna C.; Jones, Suzanne] Sarah Cannon Res Inst, GI Oncol Res, Drug Dev Unit, 250 25th Ave North,Suite 100, Nashville, TN 37203 USA. [Sznol, Mario] Yale Canc Ctr, Dept Internal Med, New Haven, CT 06511 USA. [Sznol, Mario] Yale Canc Ctr, Melanoma Unit, New Haven, CT 06511 USA. [Korski, Konstanty; Canamero, Marta; Babitski, Galina; Gaire, Fabien] Roche Diagnost GmbH, Nonnenwald 2, D-82377 Penzberg, Germany. [Mier, James; McDermott, David F.] Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215 USA. [Hodi, F. Stephen] Dana Farber Brigham & Womens Canc Ctr, 450 Brookline Ave, Boston, MA 02215 USA. RP Wallin, JJ (reprint author), Genentech Inc, 1 DNA Way, San Francisco, CA 94080 USA. EM jwallin@gene.com FU Genentech, Inc., a member of the Roche Group FX This study was sponsored by Genentech, Inc., a member of the Roche Group, which provided the study drug. Some of the authors of this manuscript are employees of Genentech/Roche. The remaining authors declare no competing financial interests. NR 28 TC 6 Z9 6 U1 7 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 AUG PY 2016 VL 7 AR 12624 DI 10.1038/ncomms12624 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DX9AU UT WOS:000384686000001 PM 27571927 ER PT J AU Chau, NG Hammerman, PS AF Chau, Nicole G. Hammerman, Peter S. TI Heads Up! Predictive Gene Signatures in Head and Neck Cancer May Be Coming Soon SO CLINICAL CANCER RESEARCH LA English DT Article ID CHEMOTHERAPY PLUS CETUXIMAB; SQUAMOUS-CELL CARCINOMA; LUNG-CANCER; EXPRESSION; SUBTYPES; EXTREME AB Cetuximab-platinum chemotherapy is used for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC); however, a minority of patients benefit. Gene expression profiling (GEP) of HNSCCs with prolonged responses to cetuximab-chemotherapy demonstrate basal subtype traits including signatures of EGFR signaling and hypoxic differentiation. GEP of short-response patients show RAS activation. (C) 2016 AACR. C1 [Chau, Nicole G.; Hammerman, Peter S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chau, Nicole G.; Hammerman, Peter S.] Harvard Med Sch, 450 Brookline Ave, Boston, MA 02215 USA. RP Hammerman, PS (reprint author), Harvard Med Sch, 450 Brookline Ave, Boston, MA 02215 USA.; Hammerman, PS (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM peter_hammerman@dfci.harvard.edu NR 12 TC 0 Z9 0 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 AUG 1 PY 2016 VL 22 IS 15 BP 3710 EP 3712 DI 10.1158/1078-0432.CCR-16-0582 PG 3 WC Oncology SC Oncology GA DU5QE UT WOS:000382265600002 PM 27129579 ER PT J AU Padron, E Dezern, A Andrade-Campos, M Vaddi, K Scherle, P Zhang, Q Ma, Y Balasis, ME Tinsley, S Ramadan, H Zimmerman, C Steensma, DP Roboz, GJ Lancet, JE List, AF Sekeres, MA Komrokji, RS AF Padron, Eric Dezern, Amy Andrade-Campos, Marcio Vaddi, Kris Scherle, Peggy Zhang, Qing Ma, Yan Balasis, Maria E. Tinsley, Sara Ramadan, Hanadi Zimmerman, Cassandra Steensma, David P. Roboz, Gail J. Lancet, Jeffrey E. List, Alan F. Sekeres, Mikkael A. Komrokji, Rami S. CA Myelodysplastic Syndrome Clinical TI A Multi-Institution Phase I Trial of Ruxolitinib in Patients with Chronic Myelomonocytic Leukemia (CMML) SO CLINICAL CANCER RESEARCH LA English DT Article ID MYELODYSPLASTIC/MYELOPROLIFERATIVE NEOPLASMS MDS/MPN; QUALITY-OF-LIFE; MYELODYSPLASTIC SYNDROMES; RESPONSE CRITERIA; MYELOID-LEUKEMIA; GENE-MUTATIONS; MYELOFIBROSIS; AZACITIDINE; INHIBITOR; PROPOSAL AB Purpose: To conduct a phase I clinical trial exploring the safety and efficacy of ruxolitinib, a JAK1/2 inhibitor, for chronic myelomonocytic leukemia (CMML). Experimental Design: Patients with CMML-1 were included without regard to previous therapy. Key exclusion criteria included an absolute neutrophil count (ANC) < 0.25 x 10(3) cells/dL and a platelet count < 35 x 10(3) cells/dL. Four cohorts were enrolled using a "rolling six" study design, with doses ranging from 5 to 20 mg twice daily of ruxolitinib in 5-mg dose escalations. Results: Between March 2013 and January 2015, 20 patients were enrolled and treated with ruxolitinib. Seventy percent of patients had the proliferative subtype and 47% had higher risk disease by the Global MD Anderson Scoring System. Eight patients (42%) received a prior hypomethylating agent. No dose-limiting toxicities for ruxolitinib were identified. One subject had grade (G) 3 thrombocytopenia with no other drug-associated G3 or G4 adverse events. The mean duration of therapy was 122 days (range, 28-409 days). Four had hematologic improvement and one patient had a partial response per 2006 International Working Group (IWG) criteria. Five of 9 patients with splenomegaly had a reduction in spleen size. Ten of 11 patients with reported disease-related symptoms had clinically meaningful or complete resolution. When combining IWG and spleen responses, a total response rate of 35% (n = 7) was identified. Correlative analysis demonstrated a reduction in inflammatory cytokines and GM-CSF-dependent STAT5 phosphorylation. Conclusions: The recommended phase II dose of ruxolitinib is 20 mg twice daily. We demonstrate that ruxolitinib has promising activity in CMML with particular benefit in those with disease-related B symptoms that warrants further study. (C) 2016 AACR. C1 [Padron, Eric; Zhang, Qing; Ma, Yan; Balasis, Maria E.; Tinsley, Sara; Ramadan, Hanadi; Lancet, Jeffrey E.; List, Alan F.; Komrokji, Rami S.] H Lee Moffitt Canc Ctr & Res Inst, Malignant Hematol, Tampa, FL USA. [Dezern, Amy] Sidney Kimmel Canc Ctr, Dept Oncol, Baltimore, MD USA. [Andrade-Campos, Marcio] CIBERER, IIS A, CIBER Enfermedades Raras, Translat Res Unit, Zaragoza, Spain. [Vaddi, Kris; Scherle, Peggy] Incyte Corp, Wilmington, DE USA. [Zimmerman, Cassandra; Sekeres, Mikkael A.] Cleveland Clin, Taussig Canc Inst, Leukemia Program, Cleveland, OH 44106 USA. [Steensma, David P.] Dana Farber Canc Inst, Dept Med Oncol, Adult Leukemia Program, Boston, MA 02115 USA. [Roboz, Gail J.] Cornell Univ, Weill Med Coll, Leukemia Program, New York, NY 10021 USA. RP Padron, E (reprint author), H Lee Moffitt Canc Ctr & Res Inst, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM eric.padron@moffitt.org FU Evans Foundation; American Society of Hematology Junior Faculty Scholar Award; Incyte Corporation FX This study was supported (in part) by research funding from the Evans Foundation (E. Padron and R.S. Komrokji), the American Society of Hematology Junior Faculty Scholar Award (E. Padron), and Incyte Corporation (E. Padron). NR 35 TC 7 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 AUG 1 PY 2016 VL 22 IS 15 BP 3746 EP 3754 DI 10.1158/1078-0432.CCR-15-2781 PG 9 WC Oncology SC Oncology GA DU5QE UT WOS:000382265600007 PM 26858309 ER PT J AU Telli, ML Timms, KM Reid, J Hennessy, B Mills, GB Jensen, KC Szallasi, Z Barry, WT Winer, EP Tung, N Isakoff, SJ Ryan, PD Greene-Colozzi, A Gutin, A Sangale, Z Iliev, D Neff, C Abkevich, V Jones, JT Lanchbury, JS Hartman, AR Garber, JE Ford, JM Silver, DP Richardson, AL AF Telli, Melinda L. Timms, Kirsten M. Reid, Julia Hennessy, Bryan Mills, Gordon B. Jensen, Kristin C. Szallasi, Zoltan Barry, William T. Winer, Eric P. Tung, NadineM. Isakoff, Steven J. Ryan, Paula D. Greene-Colozzi, April Gutin, Alexander Sangale, Zaina Iliev, Diana Neff, Chris Abkevich, Victor Jones, Joshua T. Lanchbury, Jerry S. Hartman, Anne-Renee Garber, Judy E. Ford, James M. Silver, Daniel P. Richardson, Andrea L. TI Homologous Recombination Deficiency (HRD) Score Predicts Response to Platinum-Containing Neoadjuvant Chemotherapy in Patients with Triple-Negative Breast Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID POLY(ADP-RIBOSE) POLYMERASE; OVARIAN-CANCER; DNA-DAMAGE; REPAIR; CARBOPLATIN; BRCA1; HETEROZYGOSITY; GEMCITABINE; SENSITIVITY; INHIBITION AB Purpose: BRCA1/2-mutated and some sporadic triple-negative breast cancers (TNBC) have DNA repair defects and are sensitive to DNA-damaging therapeutics. Recently, three independent DNA-based measures of genomic instability were developed on the basis of loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale state transitions (LST). Experimental Design: We assessed a combined homologous recombination deficiency (HRD) score, an unweighted sum of LOH, TAI, and LST scores, in three neoadjuvant TNBC trials of platinum-containing therapy. We then tested the association of HR deficiency, defined as HRD score >= 42 or BRCA1/2 mutation, with response to platinum-based therapy. Results: In a trial of neoadjuvant platinum, gemcitabine, and iniparib, HR deficiency predicted residual cancer burden score of 0 or I (RCB 0/I) and pathologic complete response (pCR; OR = 4.96, P = 0.0036; OR = 6.52, P = 0.0058). HR deficiency remained a significant predictor of RCB 0/I when adjusted for clinical variables (OR = 5.86, P = 0.012). In two other trials of neoadjuvant cisplatin therapy, HR deficiency predicted RCB 0/I and pCR (OR = 10.18, P = 0.0011; OR = 17.00, P = 0.0066). In a multivariable model of RCB 0/I, HR deficiency retained significance when clinical variables were included (OR = 12.08, P = 0.0017). When restricted to BRCA1/2 nonmutated tumors, response was higher in patients with high HRD scores: RCB 0/I P = 0.062, pCR P = 0.063 in the neoadjuvant platinum, gemcitabine, and iniparib trial; RCB0/I P = 0.0039, pCRP = 0.018 in the neoadjuvant cisplatin trials. Conclusions: HR deficiency identifies TNBC tumors, including BRCA1/2 nonmutated tumors more likely to respond to platinum-containing therapy. (C) 2016 AACR. C1 [Telli, Melinda L.; Jensen, Kristin C.; Ford, James M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Timms, Kirsten M.; Reid, Julia; Gutin, Alexander; Sangale, Zaina; Iliev, Diana; Neff, Chris; Abkevich, Victor; Jones, Joshua T.; Lanchbury, Jerry S.; Hartman, Anne-Renee] Myriad Genet Inc, Salt Lake City, UT USA. [Hennessy, Bryan; Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Szallasi, Zoltan] Tech Univ Denmark, Lyngby, Denmark. [Szallasi, Zoltan] Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. [Szallasi, Zoltan; Barry, William T.; Winer, Eric P.; Tung, NadineM.; Isakoff, Steven J.; Garber, Judy E.; Silver, Daniel P.; Richardson, Andrea L.] Harvard Med Sch, Boston, MA USA. [Barry, William T.; Winer, Eric P.; Greene-Colozzi, April; Garber, Judy E.; Silver, Daniel P.; Richardson, Andrea L.] Dana Farber Canc Inst, 450 Brookline Ave,SM 868B, Boston, MA 02215 USA. [Tung, NadineM.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Isakoff, Steven J.; Ryan, Paula D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Richardson, Andrea L.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Richardson, Andrea L.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Silver, DP (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,SM 868B, Boston, MA 02215 USA. EM Daniel_Silver@DFCI.Harvard.Edu FU Adelson Medical Research Foundation; AstraZeneca; Critical Outcome Technologies; Komen Research Foundation; Nanostrong; Ambry Genetics; Myriad Genetics; Natera FX G.B. Mills has ownership interest (including patents) in Catena Pharmaceuticals, PTV Ventures, Spindletop Ventures, and Myriad Genetics, reports receiving speakers bureau honoraria from AstraZeneca, Eli Lilly, ISIS Pharmaceuticals, Nuevolution, and Symphogen, is a consultant/advisory board member for Adventist Health, AstraZeneca, Blend, Catena Pharmaceuticals, Critical Outcome Technologies, HaIaI Bio Korea, ImmunoMET, Millennium Pharmaceuticals, Nuevolution, Precision Medicine, Provista Diagnostics, Signalchem Lifesciences, and Symphogen, and reports receiving commercial research grants from Adelson Medical Research Foundation, AstraZeneca, Critical Outcome Technologies, Komen Research Foundation, and Nanostrong. S.J. Isakoff is a consultant/advisory board member for Myriad Genetics. K.M. Timms, A. Gutin, and V. Abkevich have ownership interest (including patents) in Myriad Genetics Inc. J.E. Garber reports receiving commercial research grants from Ambry Genetics and Myriad Genetics. J.M. Ford reports receiving commercial research grants from Myriad Genetics and Natera. D.P. Silver and A.L. Richardson are listed as co-inventors on a patent on telomeric allelic imbalance, which is owned by the Dana-Farber Cancer Institute and licensed to Myriad Genetics. No potential conflicts of interest were disclosed by the other authors. NR 31 TC 12 Z9 12 U1 8 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 1 PY 2016 VL 22 IS 15 BP 3764 EP 3773 DI 10.1158/1078-0432.CCR-15-2477 PG 10 WC Oncology SC Oncology GA DU5QE UT WOS:000382265600009 PM 26957554 ER PT J AU Mima, K Nishihara, R Yang, JH Dou, RX Masugi, Y Shi, Y da Silva, A Cao, Y Song, MY Nowak, J Gu, MC Li, WW Morikawa, T Zhang, XH Wu, KN Baba, H Giovannucci, EL Meyerhardt, JA Chan, AT Fuchs, CS Qian, ZR Ogino, S AF Mima, Kosuke Nishihara, Reiko Yang, Juhong Dou, Ruoxu Masugi, Yohei Shi, Yan da Silva, Annacarolina Cao, Yin Song, Mingyang Nowak, Jonathan Gu, Mancang Li, Wanwan Morikawa, Teppei Zhang, Xuehong Wu, Kana Baba, Hideo Giovannucci, Edward L. Meyerhardt, Jeffrey A. Chan, Andrew T. Fuchs, Charles S. Qian, Zhi Rong Ogino, Shuji TI MicroRNA MIR21 (miR-21) and PTGS2 Expression in Colorectal Cancer and Patient Survival SO CLINICAL CANCER RESEARCH LA English DT Article ID ISLAND METHYLATOR PHENOTYPE; MOLECULAR PATHOLOGICAL EPIDEMIOLOGY; BRAF MUTATION STATUS; III COLON-CANCER; MICROSATELLITE INSTABILITY; ASPIRIN USE; LINKING INFLAMMATION; PIK3CA MUTATION; STAGE; ASSOCIATION AB Purpose: Prostaglandin-endoperoxide synthase 2 (PTGS2, cyclooxygenase-2; a target of aspirin) produces inflammatory mediator prostaglandin E-2 (PGE(2)), and contributes to colorectal neoplasia development. PTGS2-driven inflammatory responses can induce tumor expression of microRNA MIR21 (miR-21) that can increase local PGE(2) level by downregulating PGE(2)-metabolizing enzymes. We hypothesized that the prognostic association of tumor MIR21 expression level in colorectal carcinoma might depend on inflammatory tumor microenvironment and be stronger in tumors expressing high-level PTGS2. Experimental Design: Utilizing 765 rectal and colon cancer specimens in the Nurses' Health Study and the Health Professionals Follow-up Study, we measured MIR21 expression by quantitative reverse transcription PCR, and PTGS2 expression by immunohistochemistry. Cox proportional hazards regression model was used to assess statistical interaction between MIR21 and PTGS2 in colorectal cancer-specific survival analysis, con-trolling for potential confounders including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation level, and KRAS, BRAF, and PIK3CA mutations. Results: Tumor MIR21 expression level was associated with higher colorectal cancer-specific mortality (Ptrend = 0.029), and there was a statistically significant interaction between MIR21 and PTGS2 (Pinteraction = 0.0004). The association between MIR21 expression and colorectal cancer-specific mortality was statistically significant in PTGS2-high cancers (multivariable hazard ratio of the highest vs. lowest quartile of MIR21, 2.28; 95% confidence interval, 1.42-3.67; P-trend = 0.0004) but not in PTGS2-absent/low cancers (P-trend = 0.22). Conclusions: MIR21 expression level in colorectal carcinoma is associated with worse clinical outcome, and this association is stronger in carcinomas expressing high-level PTGS2, suggesting complex roles of immunity and inflammation in tumor progression. (C) 2016 AACR. C1 [Mima, Kosuke; Nishihara, Reiko; Yang, Juhong; Dou, Ruoxu; Masugi, Yohei; Shi, Yan; da Silva, Annacarolina; Gu, Mancang; Li, Wanwan; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Qian, Zhi Rong; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Mima, Kosuke; Nishihara, Reiko; Yang, Juhong; Dou, Ruoxu; Masugi, Yohei; Shi, Yan; da Silva, Annacarolina; Nowak, Jonathan; Gu, Mancang; Li, Wanwan; Zhang, Xuehong; Giovannucci, Edward L.; Meyerhardt, Jeffrey A.; Chan, Andrew T.; Fuchs, Charles S.; Qian, Zhi Rong; Ogino, Shuji] Harvard Med Sch, Boston, MA USA. [Nishihara, Reiko; Cao, Yin; Song, Mingyang; Wu, Kana; Giovannucci, Edward L.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Nishihara, Reiko; Cao, Yin; Song, Mingyang; Giovannucci, Edward L.; Ogino, Shuji] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Nishihara, Reiko] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Nowak, Jonathan; Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Div MPE Mol Pathol Epidemiol, 450 Brookline Ave,Room M422, Boston, MA 02115 USA. [Morikawa, Teppei] Univ Tokyo, Grad Sch Med, Dept Pathol, Tokyo, Japan. [Zhang, Xuehong; Giovannucci, Edward L.; Chan, Andrew T.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Baba, Hideo] Kumamoto Univ, Grad Sch Med Sci, Dept Surg Gastroenterol, Kumamoto, Japan. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. RP Ogino, S (reprint author), Brigham & Womens Hosp, Dept Pathol, Div MPE Mol Pathol Epidemiol, 450 Brookline Ave,Room M422, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu OI Masugi, Yohei/0000-0002-6952-4043 FU U.S. NIH [P01 CA87969, UM1 CA186107, P01 CA55075, UM1 CA167552, P50 CA127003, R01 CA137178, R01 CA151993, R35 CA197735, K07 CA190673]; Project P Fund; Friends of the Dana-Father Cancer Institute; Bennett Family Fund; Entertainment Industry Foundation through National Colorectal Cancer Research Alliance; Program for Advancing Strategic International Networks to Accelerate the Circulation of Talented Researchers from Japan Society for the Promotion of Science; Nurses' Health Study; Health Professionals Follow-up Study FX This work was supported by U.S. NIH grants (P01 CA87969 to M.J. Stampfer*; UM1 CA186107 to M.J. Stampfer*; P01 CA55075 to W.C. Willett*; UM1 CA167552 to W.C. Willett*; P50 CA127003 to C.S. Fuchs; R01 CA137178 to A.T. Chan.; R01 CA151993 to S. Ogino; R35 CA197735 to S. Ogino; and K07 CA190673 to R. Nishihara); and by grants from the Project P Fund, The Friends of the Dana-Father Cancer Institute, Bennett Family Fund, and the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance. K. Mima is supported by a grant from Program for Advancing Strategic International Networks to Accelerate the Circulation of Talented Researchers from Japan Society for the Promotion of Science.; These grants support tissue collection in the Nurses' Health Study and the Health Professionals Follow-up Study. Because the authors used colorectal carcinoma tissue specimens from the Nurses' Health Study and the Health Professionals Follow-up Study, the information for these grants is included even though M.J. Stampfer and W.C. Willet are not listed authors. NR 52 TC 2 Z9 2 U1 6 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 1 PY 2016 VL 22 IS 15 BP 3841 EP 3848 DI 10.1158/1078-0432.CCR-15-2173 PG 8 WC Oncology SC Oncology GA DU5QE UT WOS:000382265600017 PM 26957558 ER PT J AU Hanaford, AR Archer, TC Price, A Kahlert, UD Maciac-Zyk, J Nikkhah, G Kim, JW Ehrenberger, T Clemons, PA Dancik, V Seashore-Ludlow, B Viswanathan, V Stewart, ML Rees, MG Shamji, A Schreiber, S Fraenkel, E Pomeroy, SL Mesirov, JP Tamayo, P Eberhart, CG Raabe, EH AF Hanaford, Allison R. Archer, Tenley C. Price, Antoinette Kahlert, Ulf D. Maciac-Zyk, Jarek Nikkhah, Guido Kim, Jong Wook Ehrenberger, Tobias Clemons, Paul A. Dancik, Vlado Seashore-Ludlow, Brinton Viswanathan, Vasanthi Stewart, Michelle L. Rees, Matthew G. Shamji, Alykhan Schreiber, Stuart Fraenkel, Ernest Pomeroy, Scott L. Mesirov, Jill P. Tamayo, Pablo Eberhart, Charles G. Raabe, Eric H. TI DiSCoVERing Innovative Therapies for Rare Tumors: Combining Genetically Accurate Disease Models with In Silico Analysis to Identify Novel Therapeutic Targets SO CLINICAL CANCER RESEARCH LA English DT Article ID SET ENRICHMENT ANALYSIS; NEURAL STEM-CELLS; C-MYC; ANAPLASTIC MEDULLOBLASTOMA; DRUG-SENSITIVITY; BREAST-CANCER; MOUSE MODELS; KINASE 4/6; PD 0332991; INHIBITION AB Purpose: We used human stem and progenitor cells to develop a genetically accurate novel model of MYC-driven Group 3 medulloblastoma. We also developed a new informatics method, Disease-model Signature versus Compound-Variety Enriched Response ("DiSCoVER"), to identify novel therapeutics that target this specific disease subtype. Experimental Design: Human neural stem and progenitor cells derived from the cerebellar anlage were transduced with oncogenic elements associated with aggressive medulloblastoma. An in silico analysis method for screening drug sensitivity databases (DiSCoVER) was used in multiple drug sensitivity datasets. We validated the top hits from this analysis in vitro and in vivo. Results: Human neural stem and progenitor cells transformed with c-MYC, dominant-negative p53, constitutively active AKT and hTERT formed tumors in mice that recapitulated Group 3 medulloblastoma in terms of pathology and expression profile. DiSCoVER analysis predicted that aggressive MYC-driven Group 3 medulloblastoma would be sensitive to cyclin-dependent kinase (CDK) inhibitors. The CDK 4/6 inhibitor palbociclib decreased proliferation, increased apoptosis, and significantly extended the survival of mice with orthotopic medulloblastoma xenografts. Conclusions: We present a new method to generate genetically accurate models of rare tumors, and a companion computational methodology to find therapeutic interventions that target them. We validated our human neural stem cell model of MYC-driven Group 3 medulloblastoma and showed that CDK 4/6 inhibitors are active against this subgroup. Our results suggest that palbociclib is a potential effective treatment for poor prognosis MYC-driven Group 3 medulloblastoma tumors in carefully selected patients. (C) 2016 AACR. C1 [Hanaford, Allison R.; Price, Antoinette; Eberhart, Charles G.; Raabe, Eric H.] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD USA. [Archer, Tenley C.; Kim, Jong Wook; Ehrenberger, Tobias; Clemons, Paul A.; Schreiber, Stuart; Fraenkel, Ernest; Pomeroy, Scott L.; Mesirov, Jill P.; Tamayo, Pablo] Eli & Edythe L Broad Inst MIT & Harvard, Cambridge, MA USA. [Archer, Tenley C.; Pomeroy, Scott L.] Harvard Med Sch, Boston Childrens Hosp, Dept Neurol, Cambridge, MA USA. [Kahlert, Ulf D.; Maciac-Zyk, Jarek] Heinrich Heine Univ Hosp, Dept Neurosurg, Dusseldorf, Germany. [Nikkhah, Guido] Univ Hosp, Dept Neurosurg, Stuttgart, Germany. [Kim, Jong Wook] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ehrenberger, Tobias; Fraenkel, Ernest] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Clemons, Paul A.; Dancik, Vlado; Seashore-Ludlow, Brinton; Viswanathan, Vasanthi; Stewart, Michelle L.; Rees, Matthew G.; Shamji, Alykhan; Schreiber, Stuart] Broad Inst, Ctr Sci Therapeut, Cambridge, MA USA. [Schreiber, Stuart] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Schreiber, Stuart] Howard Hughes Med Inst, Chevy Chase, MD USA. [Mesirov, Jill P.; Tamayo, Pablo] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Mesirov, Jill P.; Tamayo, Pablo] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Raabe, Eric H.] Johns Hopkins Sch Med, Div Pediat Oncol, Baltimore, MD USA. RP Eberhart, CG (reprint author), Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD USA.; Raabe, EH (reprint author), Johns Hopkins Univ Hosp, Bloomberg 11379,1800 Orleans St, Baltimore, MD 21287 USA. EM ceberha@jhmi.edu; eraabe2@jhmi.edu OI Fraenkel, Ernest/0000-0001-9249-8181; Seashore-Ludlow, Brinton/0000-0001-8658-5967 FU NCI [P30 CA006973, R01NS055089]; NIH [R01 CA154480, R01 109467, R01GM074024] FX St. Baldrick's Foundation, Hyundai Hope on Wheels, and Giant Food Pediatric Cancer Research Fund, The Spencer Grace Foundation, The Deming Family, and The Children's Brain Tumor Foundation (to E.H. Raabe); NCI Core Grant to the Johns Hopkins SKCCC P30 CA006973, and R01NS055089 (to C.G. Eberhart), NIH R01 CA154480 (to J.P. Mesirov and P. Tamayo), NIH R01 109467 (to J.P. Mesirov and S.L. Pomeroy), NIH R01GM074024 (to J.P. Mesirov and P. Tamayo). Comprehensive Cancer Center Freiburg (to U.D. Kahlert, J. Maciaczyk, and G. Nikkhah). NCI's Cancer Target Discovery and Development (CTD2) Network U01CA176152 (to S.L. Schreiber). NR 60 TC 2 Z9 2 U1 3 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 1 PY 2016 VL 22 IS 15 BP 3903 EP 3914 DI 10.1158/1078-0432.CCR-15-3011 PG 12 WC Oncology SC Oncology GA DU5QE UT WOS:000382265600023 PM 27012813 ER PT J AU Du, YT Ter-Minassian, M Brais, L Brooks, N Waldron, A Chan, JA Lin, XH Kraft, P Christiani, DC Kulke, MH AF Du, Yeting Ter-Minassian, Monica Brais, Lauren Brooks, Nichole Waldron, Amanda Chan, Jennifer A. Lin, Xihong Kraft, Peter Christiani, David C. Kulke, Matthew H. TI Genetic associations with neuroendocrine tumor risk: results from a genome-wide association study SO ENDOCRINE-RELATED CANCER LA English DT Article DE neuroendocrine tumours; genetic risk ID CARCINOID-TUMORS; MUTATIONS; PARAGANGLIOMA; PHEOCHROMOCYTOMA; CANCER; MEN1 AB The etiology of neuroendocrine tumors remains poorly defined. Although neuroendocrine tumors are in some cases associated with inherited genetic syndromes, such syndromes are rare. The majority of neuroendocrine tumors are thought to be sporadic. We performed a genome-wide association study (GWAS) to identify potential genetic risk factors for sporadic neuroendocrine tumors. Using germline DNA from blood specimens, we genotyped 909,622 SNPs using the Affymetrix 6.0 GeneChip, in a cohort comprising 832 neuroendocrine tumor cases from Dana-Farber Cancer Institute and Massachusetts General Hospital and 4542 controls from the Harvard School of Public Health. An additional 241 controls from Dana-Farber Cancer Institute were used for quality control. We assessed risk associations in the overall cohort, and in neuroendocrine tumor subgroups. We identified no potential risk associations in the cohort overall. In the small intestine neuroendocrine tumor subgroup, comprising 293 cases, we identified risk associations with three SNPs on chromosome 12, all in strong LD. The three SNPs are located upstream of ELK3, a transcription factor implicated in angiogenesis. We did not identify clear risk associations in the bronchial or pancreatic neuroendocrine subgroups. This large-scale study provides initial evidence that presumed sporadic small intestine neuroendocrine tumors may have a genetic etiology. Our results provide a basis for further exploring the role of genes implicated in this analysis, and for replication studies to confirm the observed associations. Additional studies to evaluate potential genetic risk factors for sporadic pancreatic and bronchial neuroendocrine tumors are warranted. C1 [Du, Yeting; Ter-Minassian, Monica; Lin, Xihong; Kraft, Peter; Christiani, David C.] Harvard Sch Publ Hlth, Boston, MA USA. [Christiani, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ter-Minassian, Monica; Brais, Lauren; Brooks, Nichole; Waldron, Amanda; Chan, Jennifer A.; Kulke, Matthew H.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kulke, MH (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM matthew_kulke@dfci.harvard.edu FU Dana-Farber/Harvard SPORE Grant in Gastrointestinal Center [P50CA127003]; Goldhirsh-Yellin Foundation Fund for Neuroendocrine Tumor Research; Gitta and Saul Kurlat Fund for Neuroendocrine Tumor Research; Jane Dybowski Fund for Neuroendocrine Cancer; McIntyre Family Fund for Neuroendocrine Tumor Research; Lipson Family Fund; Murphy Family Fund for Carcinoid Tumor Research; Caring for Carcinoid Foundation; [R01CA151532] FX This work was supported by Grant #R01CA151532 (to M H K), Dana-Farber/Harvard SPORE Grant in Gastrointestinal Center (Grant #P50CA127003) and Goldhirsh-Yellin Foundation Fund for Neuroendocrine Tumor Research. The authors gratefully acknowledge additional support from the Gitta and Saul Kurlat Fund for Neuroendocrine Tumor Research, Jane Dybowski Fund for Neuroendocrine Cancer, McIntyre Family Fund for Neuroendocrine Tumor Research, Lipson Family Fund, the Murphy Family Fund for Carcinoid Tumor Research, and the Caring for Carcinoid Foundation. NR 34 TC 0 Z9 0 U1 0 U2 0 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 EI 1479-6821 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD AUG PY 2016 VL 23 IS 8 BP 587 EP 594 DI 10.1530/ERC-16-0171 PG 8 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA DX2HM UT WOS:000384188900004 PM 27492634 ER PT J AU Watson, LR Binek, A Wang, Z Mackay, C Moon, J Kedzierska, K Good-Jacobson, K Belz, G Groom, J AF Watson, L-R Binek, A. Wang, Z. Mackay, C. Moon, J. Kedzierska, K. Good-Jacobson, K. Belz, G. Groom, J. TI Migration and transcriptional regulation of TFH cell differentiation SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT International Congress of Immunology (ICI) CY AUG 21-26, 2016 CL Melbourne, AUSTRALIA C1 [Watson, L-R; Binek, A.; Groom, J.] Walter & Eliza Hall Inst Med Res, Dept Immunol & Mol Immunol, Parkville, Vic, Australia. [Wang, Z.; Kedzierska, K.] Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic, Australia. [Mackay, C.] Pfizer Inc, Inflammat & Immunol, Cambridge, MA USA. [Moon, J.] Massachusetts Gen Hosp, Charlestown, MA USA. [Moon, J.] Harvard Med Sch, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. [Good-Jacobson, K.] Monash Univ, Dept Microbiol, Clayton, Vic, Australia. [Belz, G.] Walter & Eliza Hall Inst Med Res, Dept Mol Immunol, Parkville, Vic, Australia. 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 0014-2980 EI 1521-4141 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD AUG PY 2016 VL 46 SU 1 SI SI MA 1231 BP 57 EP 57 PG 1 WC Immunology SC Immunology GA DW4KA UT WOS:000383610400114 ER PT J AU Weber, GF Chousterman, BG He, S Fenn, AM Nairz, M Anzai, A Brenner, T Uhle, F Iwamoto, Y Robbins, CS Noiret, L Maier, SL Znnchen, T Rahbari, NN Schlch, S Klotasche-Von Ameln, A Chavakis, T Weitz, J Hofer, S Weigand, MA Nahrendorf, M Weissleder, R Swirski, FK AF Weber, G. F. Chousterman, B. G. He, S. Fenn, A. M. Nairz, M. Anzai, A. Brenner, T. Uhle, F. Iwamoto, Y. Robbins, C. S. Noiret, L. Maier, S. L. Znnchen, T. Rahbari, N. N. Schlch, S. Klotasche-Von Ameln, A. Chavakis, T. Weitz, J. Hofer, S. Weigand, M. A. Nahrendorf, M. Weissleder, R. Swirski, F. K. TI Interleukin-3 amplifies acute inflammation and is a potential therapeutic target in sepsis SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT International Congress of Immunology (ICI) CY AUG 21-26, 2016 CL Melbourne, AUSTRALIA C1 [Weber, G. F.] Univ Klinikum Erlangen, FAU Erlangen Nurnberg, Dept Surg, Erlangen, Germany. [Weber, G. F.; Chousterman, B. G.; He, S.; Fenn, A. M.; Nairz, M.; Anzai, A.; Iwamoto, Y.; Robbins, C. S.; Noiret, L.; Nahrendorf, M.; Weissleder, R.; Swirski, F. K.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA USA. [Brenner, T.; Uhle, F.; Hofer, S.; Weigand, M. A.] Heidelberg Univ, Univ Klinikum Heidelberg, Dept Anaesthesiol, Heidelberg, Germany. [Maier, S. L.; Znnchen, T.; Rahbari, N. N.; Schlch, S.; Weitz, J.] Tech Univ Dresden, Dept Surg, Univ Klinikum Dresden, Dresden, Germany. [Klotasche-Von Ameln, A.; Chavakis, T.] Tech Univ Dresden, Univ Klinikum Dresden, Dept Clin Pathochem, Dresden, Germany. 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 0014-2980 EI 1521-4141 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD AUG PY 2016 VL 46 SU 1 SI SI MA 116 BP 83 EP 83 PG 1 WC Immunology SC Immunology GA DW4KA UT WOS:000383610400167 ER PT J AU Lin, C Chang, HW Tsai, PS Reinecker, HC Chiang, HS AF Lin, C. Chang, H. W. Tsai, P. S. Reinecker, H. C. Chiang, H. S. TI Lfc attenuates tumorigenesis during colitis-associated cancer SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT International Congress of Immunology (ICI) CY AUG 21-26, 2016 CL Melbourne, AUSTRALIA C1 [Lin, C.; Chiang, H. S.] Natl Taiwan Univ, Life Sci, Taipei, Taiwan. [Chang, H. W.; Tsai, P. S.] Natl Taiwan Univ, Sch Vet Med, Taipei, Taiwan. [Reinecker, H. C.] Harvard Med Sch, Gastrointestinal Unit, Massachusetts Gen Hosp, Boston, MA USA. [Reinecker, H. C.] Harvard Med Sch, Ctr Study Inflammatory Bowel Dis, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 EI 1521-4141 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD AUG PY 2016 VL 46 SU 1 SI SI MA 280 BP 371 EP 371 PG 1 WC Immunology SC Immunology GA DW4KA UT WOS:000383610400746 ER PT J AU Abdalla, T Roda, MA Li, JD Blalock, JE Gaggar, A Xu, X AF Abdalla, T. Roda, Abdul M. Li, J. -D Blalock, J. E. Gaggar, A. Xu, X. TI Prolyl endopeptidase (PE) activity in the immune system of smoking mice SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT International Congress of Immunology (ICI) CY AUG 21-26, 2016 CL Melbourne, AUSTRALIA C1 [Abdalla, T.; Li, J. -D; Blalock, J. E.; Gaggar, A.; Xu, X.] Univ Alabama Birmingham, Med, Birmingham, AL USA. [Roda, Abdul M.] Univ Utrecht, Pharmaceut Sci, Utrecht, Netherlands. [Blalock, J. E.; Gaggar, A.; Xu, X.] UAB Program Protease & Matrix Biol, Birmingham, AL USA. [Gaggar, A.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 EI 1521-4141 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD AUG PY 2016 VL 46 SU 1 SI SI MA 353 BP 407 EP 407 PG 1 WC Immunology SC Immunology GA DW4KA UT WOS:000383610401009 ER PT J AU Nirschl, C Liu, Y Kim, TG Rezai, M Dannenfelser, R Zhu, Q Chau, D Fuentes, JD Gulati, N Song-Zhao, G Krueger, J Sarin, K Troyanskaya, O Suarez-Farinas, M Anandasabapathy, N AF Nirschl, C. Liu, Y. Kim, T. -G Rezai, M. Dannenfelser, R. Zhu, Q. Chau, D. Fuentes, Ducolan J. Gulati, N. Song-Zhao, G. Krueger, J. Sarin, K. Troyanskaya, O. Suarez-Farinas, M. Anandasabapathy, N. TI Homeostatic monophagocyte signatures regulate anti-tumor immunity SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT International Congress of Immunology (ICI) CY AUG 21-26, 2016 CL Melbourne, AUSTRALIA C1 [Nirschl, C.; Liu, Y.; Kim, T. -G; Chau, D.; Song-Zhao, G.] Harvard Med Sch, Brigham & Womens Hosp, Dermatol, Boston, MA USA. [Rezai, M.; Sarin, K.] Stanford Univ, Dermatol, Stanford, CA 94305 USA. [Dannenfelser, R.; Zhu, Q.; Troyanskaya, O.] Princeton Univ, Simmons Fdn, Princeton, NJ 08544 USA. [Fuentes, Ducolan J.; Gulati, N.; Krueger, J.] Rockefeller Univ, Lab Invest Dermatol, 1230 York Ave, New York, NY 10021 USA. [Suarez-Farinas, M.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Anandasabapathy, N.] Harvard Med Sch, Brigham & Womens Hosp, Dana Farber Canc Ctr, Dermatol,Harvard Stem Cell Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 EI 1521-4141 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD AUG PY 2016 VL 46 SU 1 SI SI MA 4708 BP 510 EP 510 PG 1 WC Immunology SC Immunology GA DW4KA UT WOS:000383610401219 ER PT J AU Knoblich, K Siew, SML Parekkadan, B Turley, S Fletcher, A AF Knoblich, K. Siew, S. M. -L Parekkadan, B. Turley, S. Fletcher, A. TI Human fibroblastic reticular cells of secondary lymphoid organs regulate T cell activation and proliferation through four overlapping mechanisms SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT International Congress of Immunology (ICI) CY AUG 21-26, 2016 CL Melbourne, AUSTRALIA C1 [Knoblich, K.; Siew, S. M. -L; Fletcher, A.] Univ Birmingham, Inst Immunol & Immunotherapy, Birmingham, W Midlands, England. [Parekkadan, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Parekkadan, B.] Harvard Med Sch, Ctr Engn Med & Surg Serv, Boston, MA USA. [Turley, S.] Genentech Inc, Dept Canc Immunol, San Francisco, CA 94080 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 0014-2980 EI 1521-4141 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD AUG PY 2016 VL 46 SU 1 SI SI MA 724 BP 706 EP 707 PG 2 WC Immunology SC Immunology GA DW4KA UT WOS:000383610401613 ER PT J AU Kamphorst, AO Wieland, A Yang, S Nasti, T Zhang, R Barber, DL Konieczny, BT Koenig, L Yu, K Sica, G Owonikoko, TK Sharpe, AH Freeman, GJ Blazar, BR Turka, LA Pillai, R Ramalingam, SS Araki, K Ahmed, R AF Kamphorst, A. O. Wieland, A. Yang, S. Nasti, T. Zhang, R. Barber, D. L. Konieczny, B. T. Koenig, L. Yu, K. Sica, G. Owonikoko, T. K. Sharpe, A. H. Freeman, G. J. Blazar, B. R. Turka, L. A. Pillai, R. Ramalingam, S. S. Araki, K. Ahmed, R. TI Rescue of exhausted CD8 T cells by PD-1 targeted therapies is CD28-dependent SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT International Congress of Immunology (ICI) CY AUG 21-26, 2016 CL Melbourne, AUSTRALIA C1 [Kamphorst, A. O.; Wieland, A.; Yang, S.; Nasti, T.; Konieczny, B. T.; Araki, K.; Ahmed, R.] Emory Univ, Sch Med, Microbiol & Immunol, Emory Vaccine Ctr, Atlanta, GA USA. [Yang, S.] Cent S Univ, Xiangya Sch Med, Changsha, Hunan, Peoples R China. [Zhang, R.; Turka, L. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zhang, R.; Turka, L. A.] Harvard Med Sch, Dept Surg, Boston, MA USA. [Barber, D. L.] NIAID, Parasit Dis Lab, Bethesda, MD USA. [Koenig, L.; Yu, K.; Owonikoko, T. K.; Pillai, R.; Ramalingam, S. S.] Emory Univ, Sch Med, Dept Hematol & Med Oncol, Winship Canc Inst, Atlanta, GA USA. [Sica, G.] Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA. [Sharpe, A. H.] Harvard Med Sch, Boston, MA USA. [Freeman, G. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Blazar, B. R.] Univ Minnesota, Dept Pediat, Div Blood & Marrow Transplantat, Minneapolis, MN 55455 USA. NR 0 TC 0 Z9 0 U1 5 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 EI 1521-4141 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD AUG PY 2016 VL 46 SU 1 SI SI MA 963 BP 793 EP 793 PG 1 WC Immunology SC Immunology GA DW4KA UT WOS:000383610401788 ER PT J AU Guillerey, C de Andrade, LF Miles, K Vuckovic, S Chesi, M Bergsagel, LP Geoffrey, RH Martinet, L Smyth, MJ AF Guillerey, C. de Andrade, L. F. Miles, K. Vuckovic, S. Chesi, M. Bergsagel, L. P. Geoffrey, R. H. Martinet, L. Smyth, M. J. TI Therapeutic potential anti-CD137 mAbs in multiple myeloma SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT International Congress of Immunology (ICI) CY AUG 21-26, 2016 CL Melbourne, AUSTRALIA C1 [Guillerey, C.; de Andrade, L. F.; Miles, K.; Martinet, L.; Smyth, M. J.] QIMR Berghofer, Immunol Canc & Infect Lab, Herston, Qld, Australia. [Guillerey, C.; Smyth, M. J.] Univ Queensland, Sch Med, Herston, Qld, Australia. [de Andrade, L. F.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Vuckovic, S.] QIMR Berghofer, Bone Marrow Transplantat Lab, Herston, Qld, Australia. [Bergsagel, L. P.] Mayo Clin, Ctr Comprehens Canc, Scottsdale, AZ USA. [Martinet, L.] INSERM, UMR 1037, Canc Res Ctr Toulouse, Toulouse, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 EI 1521-4141 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD AUG PY 2016 VL 46 SU 1 SI SI MA 764 BP 1005 EP 1006 PG 2 WC Immunology SC Immunology GA DW4KA UT WOS:000383610402418 ER PT J AU Vajjhala, P Lu, A Brown, D Sagulenko, V Schroder, K Stow, J Wu, H Stacey, K AF Vajjhala, P. Lu, A. Brown, D. Sagulenko, V Schroder, K. Stow, J. Wu, H. Stacey, K. TI Molecular arrangement and activation of procaspases-1 and-8 at inflammasomes SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT International Congress of Immunology (ICI) CY AUG 21-26, 2016 CL Melbourne, AUSTRALIA C1 [Vajjhala, P.; Sagulenko, V; Stacey, K.] Univ Queensland, Sch Chem & Mol Biosci, Brisbane, Qld, Australia. [Lu, A.; Wu, H.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA USA. [Lu, A.; Wu, H.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Brown, D.; Schroder, K.; Stow, J.; Stacey, K.] Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia. 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 0014-2980 EI 1521-4141 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD AUG PY 2016 VL 46 SU 1 SI SI MA 3551 BP 1031 EP 1031 PG 1 WC Immunology SC Immunology GA DW4KA UT WOS:000383610402470 ER PT J AU Stirling, L MacLean, J AF Stirling, Leia MacLean, Julie TI Roadmap for the Development of at-Home Telemonitoring Systems to Augment Occupational Therapy SO IEEE TRANSACTIONS ON HUMAN-MACHINE SYSTEMS LA English DT Article DE Cognitive task analysis (CTA); decision making; human-computer interaction; motion primitives; situation awareness (SA) ID UPPER EXTREMITY FUNCTION; HUMAN MOTION CAPTURE; PHYSICAL REHABILITATION; MOVEMENT SMOOTHNESS; MULTIPLE-SCLEROSIS; VIRTUAL-REALITY; CEREBRAL-PALSY; LIMB FUNCTION; BRAIN-INJURY; TELEREHABILITATION AB While the literature supports the potential to provide occupational therapy through telemedicine, there are several design challenges embedded in creating an at-home telemonitoring system that can visualize the complex biomechanical data required for clinical decision making. The challenge highlighted here is the development of measures that align with current decision making methods, which will support the integration and translation of the technology. A modified cognitive task analysis methodology is presented that is composed of three segments: characterizing the subject matter, defining relevant information, and formalizing requirements. This method was implemented through observations of eight therapists over 21 patient sessions. There were nine unique modes of interaction observed between the clinician and patient. Embedded within these interactions were 14 different features monitored. Relevant performance measures were defined from these interactions to provide perception and comprehension situation awareness (SA) to the clinician about the patients task performance. Using specific activities observed during therapy sessions, sample metrics and a visualization are presented that followed from the SA requirements. Finally, the technological challenges associated with making these measurements were identified. C1 [Stirling, Leia] MIT, Dept Aeronaut & Astronaut, Inst Med Engn & Sci, Cambridge, MA 02139 USA. [MacLean, Julie] Massachusetts Gen Hosp, Dept Occupat Therapy, Boston, MA 02114 USA. RP Stirling, L (reprint author), MIT, Dept Aeronaut & Astronaut, Inst Med Engn & Sci, Cambridge, MA 02139 USA.; MacLean, J (reprint author), Massachusetts Gen Hosp, Dept Occupat Therapy, Boston, MA 02114 USA. EM leia@mit.edu; jlmaclean@partners.org FU National Science Foundation [1453141] FX This work was supported by the National Science Foundation under Award 1453141. NR 82 TC 0 Z9 0 U1 11 U2 11 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 2168-2291 EI 2168-2305 J9 IEEE T HUM-MACH SYST JI IEEE T. Hum.-Mach. Syst. PD AUG PY 2016 VL 46 IS 4 BP 569 EP 580 DI 10.1109/THMS.2015.2506729 PG 12 WC Computer Science, Artificial Intelligence; Computer Science, Cybernetics SC Computer Science GA DX3NL UT WOS:000384279700008 ER PT J AU Rannikmae, K Woodfield, R Anderson, CS Charidimou, A Chiewvit, P Greenberg, SM Jeng, JS Meretoja, A Palm, F Putaala, J Rinkel, GJE Rosand, J Rost, NS Strbian, D Tatlisumak, T Tsai, CF Wermer, MJH Werring, D Yeh, SJ Salman, RA Sudlow, CLM AF Rannikmae, Kristiina Woodfield, Rebecca Anderson, Craig S. Charidimou, Andreas Chiewvit, Pipat Greenberg, Steven M. Jeng, Jiann-Shing Meretoja, Atte Palm, Frederic Putaala, Jukka Rinkel, Gabriel J. E. Rosand, Jonathan Rost, Natalia S. Strbian, Daniel Tatlisumak, Turgut Tsai, Chung-Fen Wermer, Marieke J. H. Werring, David Yeh, Shin-Joe Salman, Rustam Al-Shahi Sudlow, Cathie L. M. TI Reliability of intracerebral hemorrhage classification systems: A systematic review SO INTERNATIONAL JOURNAL OF STROKE LA English DT Review DE Cerebral hemorrhage; cerebrovascular disorders; reproducibility of results; reliability; systematic review; classification system ID INTEROBSERVER AGREEMENT; SMASH-U; STROKE; POPULATION; PREDICTION; MORTALITY; HYPERTENSION; ASSOCIATION; MICROBLEEDS; GUIDELINES AB Background Accurately distinguishing non-traumatic intracerebral hemorrhage (ICH) subtypes is important since they may have different risk factors, causal pathways, management, and prognosis. We systematically assessed the inter- and intra-rater reliability of ICH classification systems. Methods We sought all available reliability assessments of anatomical and mechanistic ICH classification systems from electronic databases and personal contacts until October 2014. We assessed included studies' characteristics, reporting quality and potential for bias; summarized reliability with kappa value forest plots; and performed meta-analyses of the proportion of cases classified into each subtype. Summary of review We included 8 of 2152 studies identified. Inter- and intra-rater reliabilities were substantial to perfect for anatomical and mechanistic systems (inter-rater kappa values: anatomical 0.78-0.97 [six studies, 518 cases], mechanistic 0.89-0.93 [three studies, 510 cases]; intra-rater kappas: anatomical 0.80-1 [three studies, 137 cases], mechanistic 0.92-0.93 [two studies, 368 cases]). Reporting quality varied but no study fulfilled all criteria and none was free from potential bias. All reliability studies were performed with experienced raters in specialist centers. Proportions of ICH subtypes were largely consistent with previous reports suggesting that included studies are appropriately representative. Conclusions Reliability of existing classification systems appears excellent but is unknown outside specialist centers with experienced raters. Future reliability comparisons should be facilitated by studies following recently published reporting guidelines. C1 [Rannikmae, Kristiina; Woodfield, Rebecca; Salman, Rustam Al-Shahi; Sudlow, Cathie L. M.] Univ Edinburgh, Ctr Clin Brain Sci, Chancellors Bldg,49 Little France Crescent, Edinburgh EH16 4SB, Midlothian, Scotland. [Anderson, Craig S.] Royal Prince Alfred Hosp, George Inst Global Hlth, Camperdown, NSW, Australia. [Anderson, Craig S.] Univ Sydney, Sydney, NSW 2006, Australia. [Charidimou, Andreas; Werring, David] UCL Inst Neurol, Stroke Res Grp, Dept Brain Repair & Rehabil, London, England. [Charidimou, Andreas; Werring, David] Natl Hosp Neurol & Neurosurg, London, England. [Chiewvit, Pipat] Mahidol Univ, Dept Radiol, Fac Med, Siriraj Hosp, Salaya, Thailand. [Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Jeng, Jiann-Shing; Yeh, Shin-Joe] Natl Taiwan Univ Hosp, Stroke Ctr, Taipei, Taiwan. [Jeng, Jiann-Shing; Yeh, Shin-Joe] Natl Taiwan Univ Hosp, Dept Neurol, Taipei, Taiwan. [Meretoja, Atte; Putaala, Jukka; Strbian, Daniel; Tatlisumak, Turgut] Univ Helsinki, Dept Neurol, Cent Hosp, FIN-00014 Helsinki, Finland. [Meretoja, Atte] Univ Melbourne, Dept Med, Royal Melbourne Hosp, Melbourne, Vic 3010, Australia. [Meretoja, Atte] Univ Melbourne, Dept Florey, Royal Melbourne Hosp, Melbourne, Vic 3010, Australia. [Palm, Frederic] Stadt Klinikum Ludwigshafen, Dept Neurol, Ludwigshafen, Germany. [Rinkel, Gabriel J. E.] Univ Med Ctr Utrecht, Dept Neurol & Neurosurg, Brain Ctr Rudolf Magnus, Utrecht, Netherlands. [Rosand, Jonathan; Rost, Natalia S.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Tatlisumak, Turgut] Gothenburg Univ, Inst Neurosci & Physiol, Sahlgrenska Acad, S-41124 Gothenburg, Sweden. [Tatlisumak, Turgut] Sahlgrens Univ Hosp, Dept Neurol, Gothenburg, Sweden. [Tsai, Chung-Fen] Fu Jen Catholic Univ, Dept Neurol, Cardinal Tien Hosp, Sch Med, New Taipei, Taiwan. [Wermer, Marieke J. H.] Leiden Univ, Dept Neurol, Med Ctr, NL-2300 RA Leiden, Netherlands. [Sudlow, Cathie L. M.] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh EH8 9YL, Midlothian, Scotland. [Sudlow, Cathie L. M.] UK Biobank, Stockport, Lancs, England. RP Sudlow, CLM (reprint author), Univ Edinburgh, Ctr Clin Brain Sci, Chancellors Bldg,49 Little France Crescent, Edinburgh EH16 4SB, Midlothian, Scotland. EM cathie.sudlow@ed.ac.uk OI Al-Shahi Salman, Rustam/0000-0002-2108-9222 FU Edinburgh Stroke Research and Amenities Endowments Fund; UK Biobank; Scottish Funding Council; Chest Heart and Stroke Scotland; Medical Research Council; Greek State Scholarship Foundation; Stroke Association; British Heart Foundation; Higher Education Funding Council for England; National Health and Medical Research Council of Australia FX We thank M Moragas (Consultant Neurologist, NHS Lothian) for help with translating a Spanish article.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: K Rannikmae: Edinburgh Stroke Research and Amenities Endowments Fund, UK Biobank; C Sudlow: Scottish Funding Council, UK Biobank; R Woodfield: UK Biobank, Chest Heart and Stroke Scotland; R Al-Shahi Salman: Medical Research Council; A Charidimou: Greek State Scholarship Foundation, Stroke Association, British Heart Foundation; D Werring: Higher Education Funding Council for England, Stroke Association, British Heart Foundation; CS Anderson: National Health and Medical Research Council of Australia. Details of funding for P Chiewvit, S Greenberg, J-S Jeng, A Meretoja, F Palm, J Putaala, G Rinkel, J Rosand, NS Rost, D Strbian, T Tatlisumak, MJH Wermer, and S-J Yeh : found in Meretoja et al.,7 Chiewvit et al.,8 Rost et al.,16 Yeh et al.,22 Wermer et al.,24 Palm et al.25 NR 31 TC 2 Z9 2 U1 3 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD AUG PY 2016 VL 11 IS 6 BP 626 EP 636 DI 10.1177/1747493016641962 PG 11 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DS7VJ UT WOS:000380990700008 PM 27091144 ER PT J AU Jordan, JT AF Jordan, Justin T. TI Neurologic Immune-Related Adverse Events in Oncology Care SO JAMA NEUROLOGY LA English DT Editorial Material ID IPILIMUMAB; MELANOMA; ANTIBODY; THERAPY; CANCER; TRIAL C1 [Jordan, Justin T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Jordan, Justin T.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Jordan, JT (reprint author), Massachusetts Gen Hosp, Pappas Ctr Neurooncol, 55 Fruit St,Yawkey Bldg,Ste 9E, Boston, MA 02114 USA. EM jtjordan@mgh.harvard.edu NR 10 TC 0 Z9 0 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD AUG PY 2016 VL 73 IS 8 BP 907 EP 908 DI 10.1001/jamaneurol.2016.1564 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA DX2MS UT WOS:000384204900002 PM 27271299 ER PT J AU Akoudad, S Wolters, FJ Viswanathan, A de Bruijn, RF van der Lugt, A Hofman, A Koudstaal, PJ Ikram, MA Vernooij, MW AF Akoudad, Saloua Wolters, Frank J. Viswanathan, Anand de Bruijn, Renee F. van der Lugt, Aad Hofman, Albert Koudstaal, Peter J. Ikram, M. Arfan Vernooij, Meike W. TI Association of Cerebral Microbleeds With Cognitive Decline and Dementia SO JAMA NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; ROTTERDAM-SCAN; LOBAR MICROBLEEDS; BRAIN MICROBLEEDS; ISCHEMIC-STROKE; RISK-FACTORS; IMPAIRMENT; MRI; PREVALENCE; DYSFUNCTION AB IMPORTANCE Cerebral microbleeds are hypothesized downstream markers of brain damage caused by vascular and amyloid pathologic mechanisms. To date, whether their presence is associated with cognitive deterioration in the general population remains unclear. OBJECTIVE To determine whether microbleeds, and more specifically microbleed count and location, are associated with an increased risk for cognitive impairment and dementia in the general population. DESIGN, SETTING, AND PARTICIPANTS The Rotterdam Study, a prospective population-based study set in the general community, assessed the presence, number, and location of microbleeds at baseline (August 2005 to December 2011) on magnetic resonance imaging studies of the brain in 4841 participants 45 years or older. Participants underwent neuropsychological testing at 2 points a mean (SD) of 5.9 (0.6) years apart and were followed up for incident dementia throughout the study period until January 1, 2013. The association of microbleeds with cognitive decline and dementia was studied using multiple linear regression, linear mixed-effects modeling, and Cox proportional hazards. EXPOSURES Cerebral microbleed presence, location, and number. MAIN OUTCOMES AND MEASURES Cognitive decline measured by a decrease in neuropsychological test battery scores (Mini-Mental State Examination, Letter Digit Substitution Task, Word Fluency Test, Stroop test, 15-word Verbal Learning Test, and Purdue Pegboard Test) and compound scores (eg, G factor, executive function, information processing speed, memory, motor speed) and dementia. RESULTS In total, 3257 participants (1758 women [54.7%]; mean [SD] age, 59.6 [7.8] years) underwent baseline and follow-up cognitive testing. Microbleed prevalence was 15.3% (median [interquartile range] count, 1 [1-88]). The presence of more than 4 microbleeds was associated with cognitive decline. Lobar (with or without cerebellar) microbleeds were associated with a decline in executive functions (mean difference in z score, -0.31; 95% CI, -0.51 to -0.11; P = .003), information processing (mean difference in z score, -0.44; 95% CI, -0.65 to -0.22; P < .001), and memory function (mean difference in z score, -0.34; 95% CI, -0.64 to -0.03; P = .03), whereas microbleeds in other brain regions were associated with a decline in information processing and motor speed (mean difference in z score, -0.61; 95% CI, -1.05 to -0.17; P = .007). After a mean (SD) follow-up of 4.8 (1.4) years, 72 participants developed dementia, of whom 53 had Alzheimer dementia. The presence of microbleeds was associated with an increased risk for dementia after adjustment for age, sex, and educational level (hazard ratio, 2.02; 95% CI, 1.25-3.24), including Alzheimer dementia (hazard ratio, 2.10; 95% CI, 1.21-3.64). CONCLUSIONS AND RELEVANCE In the general population, a high microbleed count was associated with an increased risk for cognitive deterioration and dementia. Microbleeds thus mark the presence of diffuse vascular and neurodegenerative brain damage. C1 [Akoudad, Saloua; Wolters, Frank J.; de Bruijn, Renee F.; Hofman, Albert; Ikram, M. Arfan; Vernooij, Meike W.] Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Na28-18,Postbus 2040, NL-3000 CA Rotterdam, Netherlands. [Akoudad, Saloua; van der Lugt, Aad; Ikram, M. Arfan; Vernooij, Meike W.] Univ Med Ctr Rotterdam, Erasmus MC, Dept Radiol, Rotterdam, Netherlands. [Akoudad, Saloua; Wolters, Frank J.; de Bruijn, Renee F.; Koudstaal, Peter J.; Ikram, M. Arfan] Univ Med Ctr Rotterdam, Erasmus MC, Dept Neurol, Rotterdam, Netherlands. [Viswanathan, Anand] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. RP Ikram, MA (reprint author), Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Na28-18,Postbus 2040, NL-3000 CA Rotterdam, Netherlands. EM m.a.ikram@erasmusmc.nl FU Erasmus Medical Center and Erasmus University; Netherlands Organization for Health Research and Development; Research Institute for Diseases in the Elderly; Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission; Municipality of Rotterdam FX This study is supported by Erasmus Medical Center and Erasmus University, the Netherlands Organization for Health Research and Development, the Research Institute for Diseases in the Elderly, the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission, and the Municipality of Rotterdam. NR 49 TC 5 Z9 5 U1 6 U2 6 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 AUG PY 2016 VL 73 IS 8 BP 934 EP 943 DI 10.1001/jamaneurol.2016.1017 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA DX2MS UT WOS:000384204900014 PM 27271785 ER PT J AU Boulouis, G Morotti, A Brouwers, B Charidimou, A Jessel, MJ Auriel, E Pontes-Neto, O Ayres, A Vashkevich, A Schwab, KM Rosand, J Viswanathan, A Gurol, ME Greenberg, SM Goldstein, JN AF Boulouis, Gregoire Morotti, Andrea Brouwers, Bart Charidimou, Andreas Jessel, Michael J. Auriel, Eitan Pontes-Neto, Octavio Ayres, Alison Vashkevich, Anastasia Schwab, Kristin M. Rosand, Jonathan Viswanathan, Anand Gurol, Mahmut E. Greenberg, Steven M. Goldstein, Joshua N. TI Association Between Hypodensities Detected by Computed Tomography and Hematoma Expansion in Patients With Intracerebral Hemorrhage SO JAMA NEUROLOGY LA English DT Article ID ANGIOGRAPHY SPOT SIGN; BLOOD-PRESSURE REDUCTION; HYPERTENSIVE CEREBRAL-HEMORRHAGE; HEALTH-CARE PROFESSIONALS; ACTIVATED FACTOR-VII; CONTRAST EXTRAVASATION; STROKE ASSOCIATION; SWIRL SIGN; PREDICTION; MORTALITY AB IMPORTANCE Hematoma expansion is a potentially modifiable predictor of poor outcome following an acute intracerebral hemorrhage (ICH). The ability to identify patients with ICH who are likeliest to experience hematoma expansion and therefore likeliest to benefit from expansion-targeted treatments remains an unmet need. Hypodensities within an ICH detected by noncontrast computed tomography (NCCT) have been suggested as a predictor of hematoma expansion. OBJECTIVE To determine whether hypodense regions, irrespective of their specific patterns, are associated with hematoma expansion in patients with ICH. DESIGN, SETTING, AND PARTICIPANTS We analyzed a large cohort of 784 patients with ICH (the development cohort; 55.6% female), examined NCCT findings for any hypodensity, and replicated our findings on a different cohort of patients (the replication cohort; 52.7% female). Baseline and follow-up NCCT data from consecutive patients with ICH presenting to a tertiary care hospital between 1994 and 2015 were retrospectively analyzed. Data analyses were performed between December 2015 and January 2016. MAIN OUTCOMES AND MEASURES Hypodensities were analyzed by 2 independent blinded raters. The association between hypodensities and hematoma expansion (>6 cm(3) or 33% of baseline volume) was determined by multivariable logistic regression after controlling for other variables associated with hematoma expansion in univariate analyses with P <= .10. RESULTS A total of 1029 patients were included in the analysis. In the development and replication cohorts, 222 of 784 patients (28.3%) and 99 of 245 patients (40.4%; 321 of 1029 patients [31.2%]), respectively, had NCCT scans that demonstrated hypodensities at baseline (kappa = 0.87 for interrater reliability). In univariate analyses, hypodensities were associated with hematoma expansion (86 of 163 patients with hematoma expansion had hypodensities [52.8%], whereas 136 of 621 patients without hematoma expansion had hypodensities [21.9%]; P < .001). The association between hypodensities and hematoma expansion remained significant (odds ratio, 3.42 [95% CI, 2.21-5.31]; P < .001) in a multivariable model; other independent predictors of hematoma expansion were a CT angiography spot sign, a shorter time to CT, warfarin use, and older age. The independent predictive value of hypodensities was again demonstrated in the replication cohort (odds ratio, 4.37 [95% CI, 2.05-9.62]; P < .001). CONCLUSION AND RELEVANCE Hypodensities within an acute ICH detected on an NCCT scan may predict hematoma expansion, independent of other clinical and imaging predictors. This novel marker may help clarify the mechanism of hematoma expansion and serve as a useful addition to clinical algorithms for determining the risk of and treatment stratification for hematoma expansion. C1 [Boulouis, Gregoire; Morotti, Andrea; Brouwers, Bart; Charidimou, Andreas; Jessel, Michael J.; Auriel, Eitan; Pontes-Neto, Octavio; Ayres, Alison; Vashkevich, Anastasia; Schwab, Kristin M.; Rosand, Jonathan; Viswanathan, Anand; Gurol, Mahmut E.; Greenberg, Steven M.; Goldstein, Joshua N.] Harvard Med Sch, Massachusetts Gen Hosp, Hemorrhag Stroke Res Program, Dept Neurol,Stroke Res Ctr, 175 Cambridge St,Ste 300, Boston, MA 02114 USA. [Brouwers, Bart] Univ Utrecht, Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Neurosurg, Utrecht, Netherlands. [Rosand, Jonathan; Goldstein, Joshua N.] Harvard Med Sch, Massachusetts Gen Hosp, Div Neurocrit Care & Emergency Neurol, Boston, MA USA. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Boulouis, G (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Hemorrhag Stroke Res Program, Dept Neurol,Stroke Res Ctr, 175 Cambridge St,Ste 300, Boston, MA 02114 USA. EM gregoireboulouis@gmail.com OI Boulouis, Gregoire/0000-0001-8422-9205 FU National Institutes of Health [R01-AG026484, R01-NS073344]; J. William Fulbright Scholarship; Monahan Foundation Biomedical Research Grant FX This work was supported by National Institutes of Health grants R01-AG026484 (Dr Greenberg) and R01-NS073344 (Dr Goldstein). Dr Boulouis was supported by a J. William Fulbright Scholarship and a Monahan Foundation Biomedical Research Grant. NR 49 TC 1 Z9 1 U1 2 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 AUG PY 2016 VL 73 IS 8 BP 961 EP 968 DI 10.1001/jamaneurol.2016.1218 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA DX2MS UT WOS:000384204900017 PM 27323314 ER PT J AU Biffi, A Bailey, D Anderson, CD Ayres, AM Gurol, EM Greenberg, SM Rosand, J Viswanathan, A AF Biffi, Alessandro Bailey, Destiny Anderson, Christopher D. Ayres, Alison M. Gurol, Edip M. Greenberg, Steven M. Rosand, Jonathan Viswanathan, Anand TI Risk Factors Associated With Early vs Delayed Dementia After Intracerebral Hemorrhage SO JAMA NEUROLOGY LA English DT Article ID CEREBRAL AMYLOID ANGIOPATHY; MILD COGNITIVE IMPAIRMENT; WHITE-MATTER LESIONS; TELEPHONE INTERVIEW; ALZHEIMERS-DISEASE; APOE GENOTYPE; STATUS TICS; MICROBLEEDS; MRI; METAANALYSIS AB IMPORTANCE Patients who have experienced intracerebral hemorrhage (ICH) appear to develop cognitive impairment at high rates, both early after ICH and over the long term. OBJECTIVE To identify and compare risk factors for early and delayed dementia after ICH. DESIGN, SETTING, AND PARTICIPANTS A longitudinal study enrolled patients who had experienced ICH from January 1, 2006, to December 31, 2013. A total of 738 participants 18 years or older, without pre-ICH dementia, who presented to a tertiary care academic institution with primary ICH were included in the analyses of early post-ICH dementia (EPID). After accounting for incident dementia and mortality at 6 months, 435 participants were included in the analyses of delayed post-ICH dementia (DPID). EXPOSURES Intracerebral hemorrhage. MAIN OUTCOMES AND MEASURES Cognitive performancewas captured using the modified Telephone Interview for Cognitive Status test. Outcomes included EPID, diagnosed within 6 months after ICH, and DPID, diagnosed beyond 6 months after ICH. RESULTS Among 738 patients who had experienced ICH (mean [SD] age, 74.3 [12.1] years; 384 men [52.0%]), 140 (19.0%) developed dementia within 6 months. A total of 435 patients without dementia at 6 months were followed up longitudinally (median follow-up, 47.4 months; interquartile range, 43.4-52.1 months), with an estimated yearly incidence of dementia of 5.8% (95% CI, 5.1%-7.0%). Larger hematoma size (hazard ratio [HR], 1.47 per 10-mL increase; 95% CI, 1.09-1.97; P < .001 for heterogeneity) and lobar location of ICH (HR, 2.04; 95% CI, 1.06-3.91; P = .02 for heterogeneity) were associated with EPID but not with DPID. Educational level (HR, 0.60; 95% CI, 0.40-0.89; P < .001 for heterogeneity), incident mood symptoms (HR, 1.29; 95% CI, 1.02-1.63; P = .01 for heterogeneity), and white matter disease as defined via computed tomography (HR, 1.70; 95% CI, 1.07-2.71; P = .04 for heterogeneity) were associated with DPID but not EPID. CONCLUSIONS AND RELEVANCE Incident dementia early after ICH is strongly associated with hematoma size and location. Delayed incident dementia is frequent among patients who have experienced ICH and is not prominently associated with acute characteristics of ICH. These findings suggest the existence of heterogeneous biological mechanisms accounting for early vs delayed cognitive decline among patients who have experienced ICH. C1 [Biffi, Alessandro; Bailey, Destiny; Anderson, Christopher D.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,Mailbox CPZN 6818, Boston, MA 02114 USA. [Biffi, Alessandro; Bailey, Destiny; Anderson, Christopher D.; Ayres, Alison M.; Gurol, Edip M.; Greenberg, Steven M.; Rosand, Jonathan; Viswanathan, Anand] Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. [Biffi, Alessandro; Anderson, Christopher D.; Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Biffi, Alessandro] Massachusetts Gen Hosp, Dept Neurol, Div Stroke, Boston, MA 02114 USA. [Biffi, Alessandro] Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. [Anderson, Christopher D.; Gurol, Edip M.; Greenberg, Steven M.; Rosand, Jonathan; Viswanathan, Anand] Massachusetts Gen Hosp, Dept Neurol, Div Behav Neurol, Boston, MA 02114 USA. [Anderson, Christopher D.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Psychiat, Div Neuropsychiat, Boston, MA 02114 USA. RP Biffi, A (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,Mailbox CPZN 6818, Boston, MA 02114 USA. EM abiffi@partners.org OI Anderson, Christopher/0000-0002-0053-2002 FU National Institutes of Health [R25NS065743, R01NS063925, R01NS059727, K23NS086873, P50NS051343, R01AG26484] FX The authors' work on this study was supported by grants R25NS065743, R01NS063925, R01NS059727, K23NS086873, P50NS051343, and R01AG26484 from the National Institutes of Health. NR 31 TC 0 Z9 0 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD AUG PY 2016 VL 73 IS 8 BP 969 EP 976 DI 10.1001/jamaneurol.2016.0955 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA DX2MS UT WOS:000384204900018 PM 27295605 ER PT J AU Charidimou, A Martinez-Ramirez, S Reijmer, YD Oliveira, J Lauer, A Roongpiboonsopit, D Frosch, M Vashkevich, A Ayres, A Rosand, J Gurol, ME Greenberg, SM Viswanathan, A AF Charidimou, Andreas Martinez-Ramirez, Sergi Reijmer, Yael D. Oliveira-Filho, Jamary Lauer, Arne Roongpiboonsopit, Duangnapa Frosch, Matthew Vashkevich, Anastasia Ayres, Alison Rosand, Jonathan Gurol, Mahmut Edip Greenberg, Steven M. Viswanathan, Anand TI Total Magnetic Resonance Imaging Burden of Small Vessel Disease in Cerebral Amyloid Angiopathy An Imaging- Pathologic Study of Concept Validation SO JAMA NEUROLOGY LA English DT Article ID CORTICAL SUPERFICIAL SIDEROSIS; RECURRENT INTRACEREBRAL HEMORRHAGE; ENLARGED PERIVASCULAR SPACES; LACUNAR STROKE; MRI; MICROBLEEDS; MARKER; COHORT; PREVALENCE; DIAGNOSIS AB IMPORTANCE Cerebral amyloid angiopathy (CAA) is characteristically associated with magnetic resonance imaging (MRI) biomarkers of small vessel brain injury, including strictly lobar cerebral microbleeds, cortical superficial siderosis, centrum semiovale perivascular spaces, and white matter hyperintensities. Although these neuroimaging markers reflect distinct pathophysiologic aspects in CAA, no studies to date have combined these structural imaging features to gauge total brain small vessel disease burden in CAA. OBJECTIVES To investigate whether a composite score can be developed to capture the total brain MRI burden of small vessel disease in CAA and to explore whether this score contributes independent and complementary information about CAA severity, defined as intracerebral hemorrhage during life or bleeding-related neuropathologic changes. DESIGN, SETTING, AND PARTICIPANTS This retrospective, cross-sectional study examined a single-center neuropathologic CAA cohort of eligible patients from the Massachusetts General Hospital from January 1, 1997, through December 31, 2012. Data analysis was performed from January 2, 2015, to January 9, 2016. Patients with pathologic evidence of CAA (ie, any presence of CAA from routinely collected brain biopsy specimen, biopsy specimen at hematoma evacuation, or autopsy) and available brain MRI sequences of adequate quality, including T2-weighted, T2*-weighted gradient-recalled echo, and/or susceptibility-weighted imaging and fluid-attenuated inversion recovery sequences, were considered for the study. MAIN OUTCOMES AND MEASURES Brain MRIswere rated for lobar cerebral microbleeds, cortical superficial siderosis, centrum semiovale perivascular spaces, and white matter hyperintensities. All 4 MRI lesions were incorporated into a prespecified ordinal total small vessel disease score, ranging from 0 to 6 points. Associations with severity of CAA-associated vasculopathic changes (fibrinoid necrosis and concentric splitting of the wall), clinical presentation, number of intracerebral hemorrhages, and other imaging markers not included in the score were explored using logistic and ordinal regression. RESULTS In total, 105 patients with pathologically defined CAA were included: 52 with autopsies, 22 with brain biopsy specimens, and 31 with pathologic samples from hematoma evacuations. The mean (range) age of the patients was 73 (71-74) years, and 55 (52.4%) were women. In multivariable ordinal regression analysis, severity of CAA-associated vasculopathic changes (odds ratio, 2.40; 95% CI, 1.06-5.45; P =.04) and CAA presentation with symptomatic intracerebral hemorrhage (odds ratio, 2.23; 95% CI, 1.07-4.64; P =.03) were independently associated with the total MRI small vessel disease score. The score was associated with small, acute, diffusion-weighted imaging lesions and posterior white matter hyperintensities in adjusted analyses. CONCLUSIONS AND RELEVANCE This study provides evidence of concept validity of a total MRI small vessel disease score in CAA. After further validation, this approach can be potentially used in prospective clinical studies. C1 [Charidimou, Andreas; Martinez-Ramirez, Sergi; Reijmer, Yael D.; Oliveira-Filho, Jamary; Lauer, Arne; Roongpiboonsopit, Duangnapa; Vashkevich, Anastasia; Ayres, Alison; Rosand, Jonathan; Gurol, Mahmut Edip; Greenberg, Steven M.; Viswanathan, Anand] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Stroke Res, Hemorrhag Stroke Res Program,Dept Neurol, 175 Cambridge St,Ste 300, Boston, MA 02114 USA. [Frosch, Matthew] Harvard Med Sch, Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA USA. [Rosand, Jonathan] Harvard Med Sch, Massachusetts Gen Hosp, Div Neurocrit Care & Emergency Neurol, Boston, MA USA. [Rosand, Jonathan] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA USA. RP Charidimou, A (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Ctr Stroke Res, Hemorrhag Stroke Res Program,Dept Neurol, 175 Cambridge St,Ste 300, Boston, MA 02114 USA. EM andreas.charidimou.09@ucl.ac.uk FU National Institutes of Health [5RO1AG047975, 5P5OAG005134, 5K23AGO28726, RO1AG26484] FX This study was supported by grants 5RO1AG047975, 5P5OAG005134, 5K23AGO28726 (Dr Viswanathan), and RO1AG26484 (Dr Greenberg) from the National Institutes of Health. NR 47 TC 3 Z9 3 U1 2 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 AUG PY 2016 VL 73 IS 8 BP 994 EP 1001 DI 10.1001/jamaneurol.2016.0832 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA DX2MS UT WOS:000384204900022 PM 27366898 ER PT J AU Walcott, BP Stapleton, CJ Choudhri, O Patel, AB AF Walcott, Brian P. Stapleton, Christopher J. Choudhri, Omar Patel, Aman B. TI Flow Diversion for the Treatment of Intracranial Aneurysms SO JAMA NEUROLOGY LA English DT Review ID PIPELINE EMBOLIZATION DEVICE; ANTERIOR CHOROIDAL ARTERY; ENDOVASCULAR TREATMENT; CEREBRAL ANEURYSMS; FOLLOW-UP; SACCULAR ANEURYSMS; SURGICAL-TREATMENT; DIVERTOR STENT; EXPERIENCE; MULTICENTER AB IMPORTANCE Brain aneurysms have traditionally been treated with surgical clipping or endovascular coiling techniques. With these modalities, many large or complex aneurysms remain difficult to treat. A new option, flow diversion, is now available to treat aneurysms. OBJECTIVE To summarize the clinical progression of flow diversion technology, from an experimental treatment to a commonly used method to treat large or complex aneurysms. EVIDENCE REVIEW References for this topical review were identified by searches of PubMed and GoogleScholar between January 2000 and January 2016. The search terms aneurysm, flow diverter, stent, pipeline, FRED, SURPASS, SILK, flow diversion, and endovascular were used. Ongoing clinical trials were identified using the same search terms in the clinicaltrial. gov registry. Attention was focused on current indications, rates of complications, and areas of ongoing study in randomized clinical trials. FINDINGS Flow diversion is a treatment approved by the US Food and Drug Administration for brain aneurysms that redirects blood flow away from the aneurysm, thereby promoting growth of a new endothelial lining across the aneurysm opening. Cure rates with this technology are high and complication rates are low. CONCLUSIONS AND RELEVANCE Flow diversion is a disruptive technology that has changed the way many brain aneurysms are treated. It is currently a preferred treatment option for large or giant wide-necked proximal internal carotid artery aneurysms. Ongoing randomized studies will help to more rigorously determine the efficacy of flow diversion. C1 [Walcott, Brian P.; Choudhri, Omar] Univ Calif San Francisco, Dept Neurol Surg, 505 Parnassus Ave,Room M779, San Francisco, CA 94143 USA. [Stapleton, Christopher J.; Patel, Aman B.] Massachusetts Gen Hosp, Dept Neurol Surg, Boston, MA 02114 USA. [Stapleton, Christopher J.; Patel, Aman B.] Harvard Med Sch, Boston, MA USA. RP Walcott, BP (reprint author), Univ Calif San Francisco, Dept Neurol Surg, 505 Parnassus Ave,Room M779, San Francisco, CA 94143 USA. EM brian.walcott@ucsf.edu FU Penumbra; Covidien FX Dr Patel reported serving as a paid consultant for Penumbra and Covidien. No other disclosures were reported. NR 52 TC 1 Z9 1 U1 2 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 AUG PY 2016 VL 73 IS 8 BP 1002 EP 1008 DI 10.1001/jamaneurol.2016.0609 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA DX2MS UT WOS:000384204900023 PM 27294446 ER PT J AU Nguyen, L Hur, C AF Nguyen, Long Hur, Chin TI Proton Pump Inhibitors and Dementia Incidence SO JAMA NEUROLOGY LA English DT Letter ID RISK C1 [Nguyen, Long; Hur, Chin] Massachusetts Gen Hosp, Gastroenterol, Boston, MA 02114 USA. RP Hur, C (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM chur@mgh.harvard.edu OI Hur, Chin/0000-0002-2819-7576 NR 5 TC 0 Z9 0 U1 3 U2 3 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 AUG PY 2016 VL 73 IS 8 BP 1027 EP 1028 DI 10.1001/jamaneurol.2016.1962 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA DX2MS UT WOS:000384204900034 PM 27322752 ER PT J AU Arsava, EM Ay, H AF Arsava, Ethem Murat Ay, Hakan TI Instrument for Predicting Early Stroke Recurrence: Ambiguity and Biases Reply SO JAMA NEUROLOGY LA English DT Letter ID ISCHEMIC-STROKE; RISK C1 [Arsava, Ethem Murat] Hacettepe Univ, Dept Neurol, Fac Med, Ankara, Turkey. [Ay, Hakan] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Boston, MA USA. [Ay, Hakan] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA USA. RP Ay, H (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, 149 13th St,Room 2301, Charlestown, MA 02129 USA. EM hay@mgh.harvard.edu NR 5 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 AUG PY 2016 VL 73 IS 8 BP 1031 EP 1032 DI 10.1001/jamaneurol.2016.1727 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA DX2MS UT WOS:000384204900039 PM 27368069 ER PT J AU Heist, RS Sequist, LV Borger, D Gainor, JF Arellano, RS Le, LP Dias-Santagata, D Clark, JW Engelman, JA Shaw, AT Lafrate, AJ AF Heist, Rebecca S. Sequist, Lecia V. Borger, Darrell Gainor, Justin F. Arellano, Ronald S. Le, Long P. Dias-Santagata, Dora Clark, Jeffrey W. Engelman, Jeffrey A. Shaw, Alice T. Lafrate, A. John TI Acquired Resistance to Crizotinib in NSCLC with MET Exon 14 Skipping SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE NSCLC; MET exon 14 skipping; Acquired resistance; Targeted therapy ID CELL LUNG-CANCER; MUTATIONS; INHIBITORS; REVEALS AB Introduction: MET proto-oncogene, receptor tyrosine kinase gene (MET) exon 14 skipping is a targetable alteration in lung cancer. Treatment with MET proto-oncogene, receptor tyrosine kinase inhibitor can cause dramatic responses in patients whose cancers have MET exon 14 skipping. Little is known, however, about acquired resistance in patients with MET exon 14 skipping. Methods: Biopsy specimens obtained at baseline and at the time of progression for a patient being treated with crizotinib were compared using targeted next-generation sequencing to assess for mechanisms of resistance. Results: An acquired mutation in the MET kinase domain, D1228N, was found at time of progression on crizotinib in a patient with MET exon 14 skipping. Conclusions: One potential mechanism of acquired resistance to crizotinib in patients with MET exon 14 skipping is through second-site mutations in the MET gene. Understanding mechanisms of resistance will be important in optimizing therapy in these patients. (C) 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved. C1 [Heist, Rebecca S.; Sequist, Lecia V.; Borger, Darrell; Gainor, Justin F.; Clark, Jeffrey W.; Engelman, Jeffrey A.; Shaw, Alice T.] Massachusetts Gen Hosp, Ctr Canc, 32 Fruit St, Boston, MA 02114 USA. [Borger, Darrell; Le, Long P.; Dias-Santagata, Dora; Lafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Arellano, Ronald S.] Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. RP Heist, RS (reprint author), Massachusetts Gen Hosp, Ctr Canc, 32 Fruit St, Boston, MA 02114 USA. EM rheist@partners.org FU Be a Piece of the Solution; LungStrong; Targeting a Cure for Lung Cancer; [5R01CA164273] FX Crizotinib was provided as part of a clinical trial by Pfizer. This study was supported by funding from 5R01CA164273 (to Drs. Shaw and Engelman) and funding from the following foundations: Be a Piece of the Solution; LungStrong; and Targeting a Cure for Lung Cancer. NR 15 TC 10 Z9 11 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 AUG PY 2016 VL 11 IS 8 BP 1242 EP 1245 DI 10.1016/j.jtho.2016.06.013 PG 4 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DS8XW UT WOS:000381067300007 PM 27343442 ER PT J AU Della-Torre, E Lanzillotta, M Campochiaro, C Bozzalla, E Bozzolo, E Bandiera, A Bazzigaluppi, E Canevari, C Modorati, G Stone, JH Manfredi, A Doglioni, C AF Della-Torre, Emanuel Lanzillotta, Marco Campochiaro, Corrado Bozzalla, Emanuele Bozzolo, Enrica Bandiera, Alessandro Bazzigaluppi, Elena Canevari, Carla Modorati, Giulio Stone, John H. Manfredi, Angelo Doglioni, Claudio TI Antineutrophil cytoplasmic antibody positivity in IgG4-related disease: A case report and review of the literature SO MEDICINE LA English DT Review DE antineutrophil cytoplasmic antibodies; case report; granulomatosis with polyangiitis; IgG4; IgG4-related disease; rituximab; vasculitis ID WEGENERS-GRANULOMATOSIS; HYPERTROPHIC PACHYMENINGITIS; RETROPERITONEAL FIBROSIS; AUTOANTIBODIES ANCA; SYSTEMIC VASCULITIS; IGG SUBCLASSES; POLYANGIITIS AB Background:IgG4-related disease (IgG4-RD) is a fibroinflammatory condition characterized by serum IgG4 elevation and tissue infiltration of IgG4-positive plasma cells. Substantial overlap between IgG4-RD and antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) exists in terms of organ involvement and histopathological features. A positive ANCA assay is regarded as a highly specific finding in favor of an AAV, and generally influences away from a diagnosis of IgG4-RD. Recent reports, however, have raised the possibility that some patients with IgG4-RD are ANCA positive, thus suggesting reconsideration of the role of ANCA in the diagnostic workup. In the present work, we describe the first case of concomitant biopsy-proven IgG4-RD and granulomatosis with polyangiitis (GPA), demonstrating antiproteinase 3 (PR3) ANCA of the IgG4 subclass in the patient's serum. We also review the literature in order to provide clinicians with tools for interpreting ANCA positivity in IgG4-RD patients.Case summary:A 51-year-old woman was referred for left exopthalmos due to lacrimal gland enlargement and increased serum IgG4 concentration. IgG4-RD was suspected and further imaging studies disclosed multiple pulmonary masses in the right lung. Histological analysis of the left lacrimal gland was diagnostic for IgG4-RD, but lung biopsy showed typical features of GPA. ANCA assay was positive for anti-PR3 antibodies. Further immunofluorescence studies demonstrated anti-PR3 antibodies of IgG1 and IgG4 subclass. Treatment with rituximab induced swift remission of both IgG4-RD and GPA manifestations. We identified 9 other reports of patients with IgG4-RD and positive ANCA in the English literature, 5 cases with biopsy-proven IgG4-RD and 4 cases in whom IgG4-RD was diagnosed presumptively. Four patients had also histological evidence of concomitant AAV.Conclusion:The present work demonstrates that ANCA positivity in patients with biopsy-proven IgG4-RD should prompt the exclusion of a concomitant vasculitic process; a positive ANCA does not exclude the diagnosis of IgG4-RD; confirmation through immunoenzymatic assays of the ANCA specificity, clinical-pathological correlation, and histopathological evaluation remain crucial steps for the differential diagnosis between AAV and IgG4-RD. C1 [Della-Torre, Emanuel; Lanzillotta, Marco; Campochiaro, Corrado; Bozzalla, Emanuele; Manfredi, Angelo; Doglioni, Claudio] Univ Vita Salute San Raffaele, IRCCS San Raffaele Sci Inst, Milan, Italy. [Della-Torre, Emanuel; Manfredi, Angelo] IRCCS San Raffaele Sci Inst, Div Immunol Transplantat & Infect Dis, Milan, Italy. [Della-Torre, Emanuel; Campochiaro, Corrado; Bozzolo, Enrica; Manfredi, Angelo] IRCCS San Raffaele Sci Inst, Unit Med & Clin Immunol, Via Olgettina 60, I-20132 Milan, Italy. [Bandiera, Alessandro] IRCCS San Raffaele Sci Inst, Dept Thorac Surg, Milan, Italy. [Bazzigaluppi, Elena] IRCCS San Raffaele Sci Inst, Lab Diagnost Res, Milan, Italy. [Canevari, Carla] IRCCS San Raffaele Sci Inst, Div Nucl Med, Milan, Italy. [Modorati, Giulio] IRCCS San Raffaele Sci Inst, Dept Ophthalmol, Milan, Italy. [Stone, John H.] Harvard Med Sch, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA USA. [Doglioni, Claudio] IRCCS San Raffaele Sci Inst, Pathol Unit, Milan, Italy. RP Della-Torre, E (reprint author), IRCCS San Raffaele Sci Inst, Unit Med & Clin Immunol, Via Olgettina 60, I-20132 Milan, Italy. EM dellatorre.emanuel@hsr.it FU "Fondazione Italiana per la Ricerca sull' Artrite" (FIRA Onlus) FX This work was supported in part by a grant from the "Fondazione Italiana per la Ricerca sull' Artrite" (FIRA Onlus 2014). NR 36 TC 0 Z9 0 U1 8 U2 8 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 AUG PY 2016 VL 95 IS 34 AR e4633 DI 10.1097/MD.0000000000004633 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA DX0DV UT WOS:000384032900039 PM 27559962 ER PT J AU Dams, J Balzer-Geldsetzer, M Siebert, U Deuschl, G Schuepbach, WMM Krack, P Timmermann, L Schnitzler, A Reese, JP Dodel, R AF Dams, Judith Balzer-Geldsetzer, Monika Siebert, Uwe Deuschl, Guenther Schuepbach, W. M. Michael Krack, Paul Timmermann, Lars Schnitzler, Alfons Reese, Jens-Peter Dodel, Richard CA EARLYSTIM-Investigators TI Cost-effectiveness of neurostimulation in Parkinson's disease with early motor complications SO MOVEMENT DISORDERS LA English DT Article DE early Parkinson's disease; dyskinesia; deep brain stimulation; Markov model; cost-utility analysis ID DEEP-BRAIN-STIMULATION; SUBTHALAMIC NUCLEUS; FOLLOW-UP; METAANALYSIS; PREDICTORS; OUTCOMES; GERMANY; TRIAL; LIFE AB BackgroundRecent research efforts have focused on the effects of deep brain stimulation of the subthalamic nucleus (STN DBS) for selected patients with mild-to-moderate PD experiencing motor complications. ObjectivesWe assessed the cost utility of subthalamic DBS compared with the best medical treatment for German patients below the age of 61 with early motor complications of PD. MethodsWe applied a previously published Markov model that integrated health utilities based on EuroQoL and direct costs over patients' lifetime adjusted to the German health care payer perspective (year of costing: 2013). Effectiveness was evaluated using the Parkinson's Disease Questionnaire 39 summary index. We performed sensitivity analyses to assess uncertainty. ResultsIn the base-case analysis, the incremental cost-utility ratio for STN DBS compared to best medical treatment was 22,700 Euros per quality-adjusted life year gained. The time to, and costs for, battery exchange had a major effect on the incremental cost-utility ratios, but never exceeded a threshold of 50,000 Euros per quality-adjusted life year. ConclusionsOur decision analysis supports the fact that STN DBS at earlier stages of the disease is cost-effective in patients below the age of 61 when compared with the best medical treatment in the German health care system. This finding was supported by detailed sensitivity analyses reporting robust results. Whereas the EARLYSTIM study has shown STN DBS to be superior to medical therapy with respect to quality of life for patients with early motor complications, this further analysis has shown its cost-effectiveness. (c) 2016 International Parkinson and Movement Disorder Society C1 [Dams, Judith; Balzer-Geldsetzer, Monika; Dodel, Richard] Univ Marburg, Dept Neurol, Baldingerstr, D-35043 Marburg, Germany. [Siebert, Uwe] UMIT Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth Hlth Serv Res & HealthTechnol Asse, Halle, Germany. [Siebert, Uwe] Harvard Med Sch, Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA USA. [Siebert, Uwe] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Siebert, Uwe] Harvard Chan Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Deuschl, Guenther] Univ Kiel, Dept Neurol, Kiel, Germany. [Schuepbach, W. M. Michael] Univ Paris 06, Inst Cerveau & Moelle Epiniere, Ctr Invest Clin 9503, AP HP,Dept Neurol, Paris, France. [Schuepbach, W. M. Michael] CHU Pitie Salpetriere, INSERM, Paris, France. [Schuepbach, W. M. Michael] Univ Hosp Bern, Dept Neurol, Movement Disorders Ctr, Bern, Switzerland. [Schuepbach, W. M. Michael] Univ Bern, Bern, Switzerland. [Krack, Paul] Grenoble Alpes Univ, Univ Hosp INSERM U836, Dept Neurol, St Martin Dheres, France. [Timmermann, Lars] Univ Hosp Cologne, Dept Neurol, Cologne, Germany. [Schnitzler, Alfons] Univ Dusseldorf, Inst Clin Neurosci & Med Psychol, Dusseldorf, Germany. [Reese, Jens-Peter] Univ Marburg, Dept Med Sociol & Social Med, Marburg, Germany. [Dodel, Richard] Univ Duisburg Essen, Dept Geriatr, Essen, Germany. RP Dodel, R (reprint author), Univ Marburg, Dept Neurol, Baldingerstr, D-35043 Marburg, Germany. EM dodel@med.uni-marburg.de OI Volkmann, Jens/0000-0002-9570-593X FU Teva; Medtronic; Boston Scientific; Orkyn; Novartis; UGH; LVL; St Jude FX G.D. has board membership for Teva Pharmaceuticals and Novartis received lecture fees from Teva M.S. has received research support from Medtronic and Boston Scientific, lecture fees from Medtronic, and travel reimbursements from Zambon, Merz Pharma, Boston Scientific, and Medtronic and has been serving as a consultant for Medtronic and Aleva. P.K. has received research support from Orkyn, Novartis, UGH, Medtronic, LVL, Boston Scientific, and St Jude and honoraria for lecturing or consultation from the International Parkinson and Movement Disorder Society, Lundbeck, Boehringer Ingelheim, Novartis, UGH, Medtronic, Orkyn, Abbott, Orion, TEVA, and Boston Scientific. L.I. has served as a consultant for Medtronic, Boston Scientific, and St. Jude and received speakers' honoraria in symposia sponsored by Medtronic, Boston Scientific, and St. Jude. The institution of L.T. received unrestricted research grants by Medtronic and Boston Scientific. A.S. has served as a consultant for Medtronic Inc, Boston Scientific, and St. Jude Medical and received lecture fees from Boston Scientific, St. Jude Medical, and Medtronic Inc. NR 35 TC 1 Z9 1 U1 5 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD AUG PY 2016 VL 31 IS 8 BP 1183 EP 1191 DI 10.1002/mds.26740 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA DU9ST UT WOS:000382558800019 PM 27506638 ER PT J AU DeLisi, LE AF DeLisi, Lynn E. TI Signing off as Editor-in-Chief SO SCHIZOPHRENIA RESEARCH LA English DT Editorial Material ID SCHIZOPHRENIA; PATHOLOGY C1 [DeLisi, Lynn E.] Harvard Med Sch, VA Boston Healthcare Syst, Psychiat, 940 Belmont Ave, Brockton, MA 02301 USA. RP DeLisi, LE (reprint author), Harvard Med Sch, VA Boston Healthcare Syst, Psychiat, 940 Belmont Ave, Brockton, MA 02301 USA. EM Lynn_DeLisi@hms.harvard.edu NR 6 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD AUG PY 2016 VL 175 IS 1-3 BP 2 EP 3 DI 10.1016/j.schres.2016.06.026 PG 2 WC Psychiatry SC Psychiatry GA DS5GA UT WOS:000380808200002 PM 27444218 ER PT J AU Raja, AS Mower, WR Nishijima, DK Hendey, GW Baumann, BM Medak, AJ Rodriguez, RM AF Raja, Ali S. Mower, William R. Nishijima, Daniel K. Hendey, Gregory W. Baumann, Brigitte M. Medak, Anthony J. Rodriguez, Robert M. TI Prevalence and Diagnostic Performance of Isolated and Combined NEXUS Chest CT Decision Criteria SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID MULTISYSTEM TRAUMA PATIENTS; BLUNT TRAUMA; COMPUTED-TOMOGRAPHY; OBVIOUS SIGNS; INJURY; RADIOGRAPHY; INSTRUMENT AB Objectives: The use of chest computed tomography (CT) to evaluate emergency department patients with adult blunt trauma is rising. The NEXUS Chest CT decision instruments are highly sensitive identifiers of adult blunt trauma patients with thoracic injuries. However, many patients without injury exhibit one of more of the criteria so cannot be classified "low risk." We sought to determine screening performance of both individual and combined NEXUS Chest CT criteria as predictors of thoracic injury to inform chest CT imaging decisions in "non-low-risk" patients. Methods: This was a secondary analysis of data on patients in the derivation and validation cohorts of the prospective, observational NEXUS Chest CT study, performed September 2011 to May 2014 in 11 Level I trauma centers. Institutional review board approval was obtained at all study sites. Adult blunt trauma patients receiving chest CT were included. The primary outcome was injury and major clinical injury prevalence and screening performance in patients with combinations of one, two, or three of seven individual NEXUS Chest CT criteria. Results: Across the 11 study sites, rates of chest CT performance ranged from 15.5% to 77.2% (median = 43.6%). We found injuries in 1,493/5,169 patients (28.9%) who had chest CT; 269 patients (5.2%) had major clinical injury (e.g., pneumothorax requiring chest tube). With sensitivity of 73.7 (95% confidence interval [CI] = 68.1 to 78.6) and specificity of 83.9 (95% CI = 83.6 to 84.2) for major clinical injury, abnormal chest-x-ray (CXR) was the single most important screening criterion. When patients had only abnormal CXR, injury and major clinical injury prevalences were 60.7% (95% CI = 52.2% to 68.6%) and 12.9% (95% CI = 8.3% to 19.4%), respectively. Injury and major clinical injury prevalences when any other single criterion alone (other than abnormal CXR) was present were 16.8% (95% CI = 15.2% to 18.6%) and 1.1% (95% CI = 0.1% to 1.8%), respectively. Injury and major clinical injury prevalences among patients when two and three criteria (not abnormal CXR) were present were 25.5% (95% CI = 23.1% to 28.0%) and 3.2% (95% CI = 2.3% to 4.4%) and 34.9% (95% CI = 31.0% to 39.0%) and 2.7% (95% CI = 1.6% to 4.5%), respectively. Conclusions: We recommend that clinicians check for the six clinical NEXUS Chest CT criteria and review the CXR (if obtained). If patients have one clinical criterion (other than abnormal CXR), they will have a very low risk of clinically major injury. We recommend that clinicians discuss the potential risks and benefit of chest CT in these cases. The risks of injury and major clinical injury rise incrementally with more criteria, rendering the risk/benefit ratio toward performing CT in most cases. If the patient has an abnormal CXR, the risks of major clinical injury and minor injury are considerably higher than with the other criteria-chest CT may be indicated in cases requiring greater anatomic detail and injury characterization. (C) 2016 by the Society for Academic Emergency Medicine C1 [Raja, Ali S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Raja, Ali S.] Harvard Med Sch, Boston, MA 02115 USA. [Mower, William R.] Univ Calif Los Angeles, Dept Emergency Med, Los Angeles, CA USA. [Nishijima, Daniel K.] Univ Calif Davis, Dept Emergency Med, Davis, CA 95616 USA. [Hendey, Gregory W.] San Francisco Fresno Med Educ Program, Dept Emergency Med, San Francisco, CA USA. [Baumann, Brigitte M.] Rowan Univ, Cooper Med Sch, Dept Emergency Med, Camden, NJ USA. [Medak, Anthony J.] Univ Calif San Diego, Sch Med, Dept Emergency Med, San Diego, CA 92103 USA. [Rodriguez, Robert M.] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA. RP Raja, AS (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.; Raja, AS (reprint author), Harvard Med Sch, Boston, MA 02115 USA. EM ASRaja@partners.org FU University of California Center for Health Quality and Innovation (CHQI) FX Funded by University of California Center for Health Quality and Innovation (CHQI). NR 22 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD AUG PY 2016 VL 23 IS 8 BP 863 EP 869 DI 10.1111/acem.13010 PG 7 WC Emergency Medicine SC Emergency Medicine GA DW1BQ UT WOS:000383378200003 PM 27163732 ER PT J AU Collins, SP Levy, PD Martindale, JL Dunlap, ME Storrow, AB Pang, PS Albert, NM Felker, GM Fermann, GJ Fonarow, GC Givertz, MM Hollander, JE Lanfear, DE Lenihan, DJ Lindenfeld, JM Peacock, WF Sawyer, DB Teerlink, JR Butler, J AF Collins, Sean P. Levy, Phillip D. Martindale, Jennifer L. Dunlap, Mark E. Storrow, Alan B. Pang, Peter S. Albert, Nancy M. Felker, G. Michael Fermann, Gregory J. Fonarow, Gregg C. Givertz, Michael M. Hollander, Judd E. Lanfear, David E. Lenihan, Daniel J. Lindenfeld, JoAnn M. Peacock, W. Frank Sawyer, Douglas B. Teerlink, John R. Butler, Javed TI Clinical and Research Considerations for Patients With Hypertensive Acute Heart Failure: A Consensus Statement from the Society for Academic Emergency Medicine and the Heart Failure Society of America Acute Heart Failure Working Group SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID CARDIOGENIC PULMONARY-EDEMA; WORSENING RENAL-FUNCTION; SCANDINAVIAN ENALAPRIL SURVIVAL; HAND-CARRIED ULTRASOUND; BLOOD-PRESSURE; ISOSORBIDE-DINITRATE; NONINVASIVE VENTILATION; FLUID ACCUMULATION; TRANSDERMAL NITROGLYCERIN; INTRAVENOUS ENALAPRILAT AB Management approaches for patients in the emergency department (ED) who present with acute heart failure (AHF) have largely focused on intravenous diuretics. Yet, the primary pathophysiologic derangement underlying AHF in many patients is not solely volume overload. Patients with hypertensive AHF (H-AHF) represent a clinical phenotype with distinct pathophysiologic mechanisms that result in elevated ventricular filling pressures. To optimize treatment response and minimize adverse events in this subgroup, we propose that clinical management be tailored to a conceptual model of disease that is based on these mechanisms. This consensus statement reviews the relevant pathophysiology, clinical characteristics, approach to therapy, and considerations for clinical trials in ED patients with H-AHF. (C) 2016 by the Society for Academic Emergency Medicine C1 [Collins, Sean P.; Storrow, Alan B.] Vanderbilt Univ, Dept Emergency Med, 221 Kirkland Hall, Nashville, TN 37235 USA. [Levy, Phillip D.] Wayne State Univ, Dept Emergency Med, Detroit, MI USA. [Martindale, Jennifer L.] SUNY Downstate, Dept Emergency Med, Brooklyn, NY USA. [Dunlap, Mark E.] Case Western Univ, Dept Med, Cleveland, OH USA. [Pang, Peter S.] Indiana Univ, Dept Emergency Med, Indianapolis, IN 46204 USA. [Albert, Nancy M.] Cleveland Clin, Dept Med, Cleveland, OH 44106 USA. [Felker, G. Michael] Duke Univ, Dept Med, Durham, NC USA. [Fermann, Gregory J.] Univ Cincinnati, Dept Emergency Med, Cincinnati, OH USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Givertz, Michael M.] Harvard Med Sch, Dept Med, Boston, MA USA. [Hollander, Judd E.] Thomas Jefferson Univ, Dept Emergency Med, Philadelphia, PA 19107 USA. [Lanfear, David E.] Henry Ford Hlth Syst, Dept Med, Detroit, MI USA. [Lenihan, Daniel J.; Lindenfeld, JoAnn M.] Vanderbilt Univ, Dept Med, Nashville, TN USA. [Peacock, W. Frank] Baylor Coll Med, Dept Emergency Med, Houston, TX 77030 USA. [Sawyer, Douglas B.] Maine Med Ctr, Dept Med, Portland, ME 04102 USA. [Teerlink, John R.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Butler, Javed] SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA. RP Collins, SP (reprint author), Vanderbilt Univ, Dept Emergency Med, 221 Kirkland Hall, Nashville, TN 37235 USA. EM sean.collins@vanderbilt.edu NR 91 TC 0 Z9 0 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD AUG PY 2016 VL 23 IS 8 BP 922 EP 931 DI 10.1111/acem.13025 PG 10 WC Emergency Medicine SC Emergency Medicine GA DW1BQ UT WOS:000383378200011 PM 27286136 ER PT J AU Neogi, T Choi, HK AF Neogi, Tuhina Choi, Hyon K. TI Pursuit of a Dual-Benefit Antigout Drug: A First Look at Arhalofenate SO ARTHRITIS & RHEUMATOLOGY LA English DT Editorial Material ID NUTRITION EXAMINATION SURVEY; OF-RHEUMATOLOGY GUIDELINES; NATIONAL-HEALTH; GOUT; MANAGEMENT; HYPERURICEMIA; PREVALENCE; AGENT C1 [Neogi, Tuhina] Boston Univ, Sch Med, Boston, MA 02118 USA. [Choi, Hyon K.] Boston Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02118 USA. [Choi, Hyon K.] Harvard Med Sch, Boston, MA USA. RP Neogi, T (reprint author), Boston Univ, Sch Med, Clin Epidemiol Res & Training Unit, 650 Albany St,X Bldg,Suite 200, Boston, MA 02118 USA. EM tneogi@bu.edu FU NIAMS NIH HHS [P60 AR047785] NR 16 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD AUG PY 2016 VL 68 IS 8 BP 1793 EP 1796 DI 10.1002/art.39687 PG 4 WC Rheumatology SC Rheumatology GA DW2UX UT WOS:000383498400001 PM 26990165 ER PT J AU Baker, JF Sauer, BC Cannon, GW Teng, CC Michaud, K Ibrahim, S Jorgenson, E Davis, L Caplan, L Cannella, A Mikuls, TR AF Baker, Joshua F. Sauer, Brian C. Cannon, Grant W. Teng, Chia-Chen Michaud, Kaleb Ibrahim, Said Jorgenson, Erik Davis, Lisa Caplan, Liron Cannella, Amy Mikuls, Ted R. TI Changes in Body Mass Related to the Initiation of Disease-Modifying Therapies in Rheumatoid Arthritis SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID WEIGHT CHANGE; RISK-FACTORS; US VETERANS; INDEX; LEFLUNOMIDE; METHOTREXATE; MORTALITY; ACCURACY; COMORBIDITY; INHIBITORS AB Objective. Unintentional weight loss is important and can be predictive of long-term outcomes in patients with rheumatoid arthritis (RA). This study was undertaken to assess how primary therapies for RA may influence changes in body mass index (BMI) in RA patients from a large administrative database. Methods. Unique dispensing episodes of methotrexate, prednisone, leflunomide, and tumor necrosis factor inhibitors (TNFi) administered to RA patients were identified from the US Department of Veterans Affairs pharmacy databases. Values for C-reactive protein (CRP) level and BMI closest to the time point within 30 days of the treatment course start date and at follow-up time points were linked. Missing laboratory values were imputed. Weight loss was defined as a decrease in BMI of >1 kg/m(2). Regression models were used to evaluate changes in BMI during each drug treatment as compared to treatment with methotrexate. To assess the impact of confounding by indication, propensity scores for use of each drug were incorporated in analyses using matched-weighting techniques. Results. In total, 52,662 treatment courses in 32,859 RA patients were identified. At 6 months from the date of prescription fill, weight gain was seen among patients taking methotrexate, those taking prednisone, and those taking TNFi. On average, compared to methotrexate-treated patients, prednisone-treated patients had significantly more weight gain, while leflunomide-treated patients demonstrated weight loss. In multivariable models, more weight loss (beta = 20.41 kg/m(2), 95% confidence interval [95% CI] -0.46, -0.36; P < 0.001) and a greater risk of weight loss (odds ratio 1.73, 95% CI 1.55, 1.79; P < 0.001) were evident among those receiving leflunomide compared to those receiving methotrexate. Treatment with prednisone was associated with greater weight gain (beta = 0.072 kg/m(2), 95% CI 0.042, 0.10; P < 0.001). These associations persisted in analyses adjusted for propensity scores and in sensitivity analyses. Conclusion. Leflunomide is associated with significantly more, but modest, weight loss, while prednisone is associated with greater weight gain compared to other therapies for RA. C1 [Baker, Joshua F.; Jorgenson, Erik] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Baker, Joshua F.; Ibrahim, Said; Jorgenson, Erik] Univ Penn, Philadelphia, PA 19104 USA. [Sauer, Brian C.; Cannon, Grant W.; Teng, Chia-Chen] Salt Lake City VA Med Ctr, Salt Lake City, UT USA. [Sauer, Brian C.; Cannon, Grant W.; Teng, Chia-Chen] Univ Utah, Salt Lake City, UT USA. [Michaud, Kaleb; Cannella, Amy; Mikuls, Ted R.] Univ Nebraska Med Ctr, Omaha, NE USA. [Michaud, Kaleb] Natl Data Bank Rheumat Dis, Wichita, KS USA. [Ibrahim, Said] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Davis, Lisa; Caplan, Liron] Denver VA Med Ctr, Denver, CO USA. [Cannella, Amy; Mikuls, Ted R.] VA Nebraska Western Iowa Hlth Care Syst, Omaha, NE USA. RP Baker, JF (reprint author), Hosp Univ Penn, Div Rheumatol, Dept Med, 5 White Bldg,3600 Spruce St, Philadelphia, PA 19104 USA. EM bakerjo@uphs.upenn.edu FU Veterans Affairs Clinical Science Research and Development Career Development Award [IK2-CX000955]; K24 Mid-Career Development Award from National Institutes of Musculoskeletal and Skin Disorders [1K24-AR-055259-01]; Veterans Affairs Merit Award FX Supported by a Veterans Affairs Clinical Science Research and Development Career Development Award (IK2-CX000955 to Dr. Baker), a K24 Mid-Career Development Award from the National Institutes of Musculoskeletal and Skin Disorders (1K24-AR-055259-01 to Dr. Ibrahim), and a Veterans Affairs Merit Award (to Dr. Mikuls). NR 35 TC 1 Z9 1 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD AUG PY 2016 VL 68 IS 8 BP 1818 EP 1827 DI 10.1002/art.39647 PG 10 WC Rheumatology SC Rheumatology GA DW2UX UT WOS:000383498400006 PM 26882094 ER PT J AU Wolf, BJ Spainhour, JC Arthur, JM Janech, MG Petri, M Oates, JC AF Wolf, Bethany J. Spainhour, John C. Arthur, John M. Janech, Michael G. Petri, Michelle Oates, Jim C. TI Development of Biomarker Models to Predict Outcomes in Lupus Nephritis SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID MONOCYTE CHEMOATTRACTANT; ERYTHEMATOSUS; CLASSIFICATION; URINE; CELLS; INFLAMMATION; CHEMOKINES; PROTEIN-1; EFFICACY; SAFETY AB Objective. The American College of Rheumatology guidelines for the treatment of lupus nephritis recommend change in induction therapy when response to therapy has not occurred within 6 months. Response is not defined, and renal fibrosis can occur while waiting for this end point. Therefore, a decision support tool to better define response is needed to guide clinicians when starting patients on therapy. This study was undertaken to identify biomarker models with sufficient predictive power to develop such a tool. Methods. Urine samples from 140 patients with biopsy-proven lupus nephritis who had not yet started induction therapy were analyzed for a panel of urinary biomarkers. Univariate receiver operating characteristic (ROC) curves were generated for each individual biomarker and compared to the ROC area under the curve values from machine learning models developed using random forest algorithms. Biomarker models of outcome developed with novel markers in addition to clinical markers were compared to those developed with traditional clinical markers alone. Results. Models developed with the combined traditional and novel biomarker panels demonstrated clinically meaningful predictive power. Markers most predictive of response were chemokines, cytokines, and markers of cellular damage. Conclusion. This is the first study to demonstrate the power of low-abundance biomarker panels and machine learning algorithms for predicting lupus nephritis outcomes. This is a critical first step in research to develop clinically meaningful decision support tools. C1 [Wolf, Bethany J.; Spainhour, John C.; Arthur, John M.; Janech, Michael G.; Oates, Jim C.] Med Univ South Carolina, Charleston, SC USA. [Spainhour, John C.] Georgia Inst Technol, Atlanta, GA 30332 USA. [Spainhour, John C.] Emory Univ, Atlanta, GA 30322 USA. [Arthur, John M.; Janech, Michael G.; Oates, Jim C.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Petri, Michelle] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Oates, JC (reprint author), Dept Med, Div Rheumatol & Immunol, Clin Sci Bldg,96 Jonathan Lucas St,Suite 816, Charleston, SC 29425 USA. EM oatesjc@musc.edu FU VA Merit Award [1I01CX000218-01]; NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases [R21-AR-051719]; Medical University of South Carolina General and Clinical Research Center [M01-RR-001070]; South Carolina Clinical and Translational Research Institute; academic home at the Medical University of South Carolina (through NIH/National Center for Research Resources) [UL1-RR-029882]; Multidisciplinary Clinical Research Center at the Medical University of South Carolina [P60-A-R062755]; VA Research Enhancement Award Program award; NephCure Kidney International Young Investigator Career Development Award; Hopkins Lupus Cohort [AR-43727]; NIH/National Center for Research Resources [UL1-RR-025005] FX Supported in part by a VA Merit Award (1I01CX000218-01), NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases grant R21-AR-051719, the Medical University of South Carolina General and Clinical Research Center (through NIH grant M01-RR-001070), the South Carolina Clinical and Translational Research Institute, with an academic home at the Medical University of South Carolina (through NIH/National Center for Research Resources grant number UL1-RR-029882), and the Multidisciplinary Clinical Research Center at the Medical University of South Carolina (through NIH grant P60-A-R062755). Support also came from a VA Research Enhancement Award Program award. Subject material (urine samples for biomarker analysis and clinical data) were provided by Genentech (from the Lupus Nephritis Assessment of Rituximab [LUNAR] study; ClinicalTrials.gov identifier: NCT00282347) and Bristol-Myers Squibb (from the Abatacept in Lupus Nephritis study; ClinicalTrials.gov identifier: NCT00430677) and their investigators. Dr. Janech's work was supported by a NephCure Kidney International Young Investigator Career Development Award. Dr. Petri's work was supported by the Hopkins Lupus Cohort (through NIH grant AR-43727) and NIH/National Center for Research Resources grant UL1-RR-025005. NR 38 TC 2 Z9 2 U1 4 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD AUG PY 2016 VL 68 IS 8 BP 1955 EP 1963 DI 10.1002/art.39623 PG 9 WC Rheumatology SC Rheumatology GA DW2UX UT WOS:000383498400020 PM 26867033 ER PT J AU Saag, KG Whelton, A Becker, MA MacDonald, P Hunt, B Gunawardhana, L AF Saag, Kenneth G. Whelton, Andrew Becker, Michael A. MacDonald, Patricia Hunt, Barbara Gunawardhana, Lhanoo TI Impact of Febuxostat on Renal Function in Gout Patients With Moderate-to-Severe Renal Impairment SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; URIC-ACID; HYPERURICEMIA; URATE; ALLOPURINOL; GUIDELINES; EFFICACY; SAFETY; CLASSIFICATION; COMORBIDITIES AB Objective. Renal impairment is a risk factor for gout and a barrier to optimal gout management. We undertook this exploratory study to obtain data that have been heretofore limited regarding the safety and efficacy of febuxostat in patients with moderate-to-severe renal impairment (estimated glomerular filtration rate [GFR] 15-50 ml/minute/1.73m(2)). Methods. Ninety-six gout patients with moderate-to-severe renal impairment were enrolled in a 12-month multicenter, randomized, double-blind, placebo-controlled study. Patients were randomly assigned at a 1: 1: 1 ratio to receive 30 mg febuxostat twice daily, 40/80 mg febuxostat once daily, or placebo. The primary efficacy end point was the change in serum creatinine (Cr) level from baseline to month 12. Secondary end points included the change in estimated GFR from baseline to month 12 and the proportion of patients with a serum uric acid (UA) level of <6.0 mg/dl at month 12. Results. At month 12, there were no significant differences in the change in serum Cr level from baseline, or in the change in estimated GFR from baseline, in either febuxostat group compared to the placebo group. The proportion of patients with a serum UA level of <6.0 mg/dl at month 12 was significantly greater in both febuxostat groups compared to the placebo group (both P < 0.001). At least 1 treatment-emergent adverse event (TEAE) occurred in 78.1% of patients receiving 30 mg febuxostat twice daily, 87.5% of patients receiving 40/80 mg febuxostat once daily, and 78.1% of patients receiving placebo. TEAEs most frequently involved the categories of renal failure and impairment and renal function analyses. Conclusion. Febuxostat proved to be efficacious in serum UA reduction and was well tolerated in gout patients with moderate-to-severe renal impairment. Patients randomly assigned to receive febuxostat demonstrated significantly lower serum UA levels and no significant deterioration in renal function. C1 [Saag, Kenneth G.] Birmingham VA Med Ctr, Birmingham, AL USA. [Saag, Kenneth G.] Univ Alabama Birmingham, Birmingham, AL USA. [Whelton, Andrew] Johns Hopkins Univ, Baltimore, MD USA. [Becker, Michael A.] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. [MacDonald, Patricia; Hunt, Barbara; Gunawardhana, Lhanoo] Takeda Pharmaceut, Deerfield, IL USA. RP Saag, KG (reprint author), Univ Alabama Birmingham, Div Clin Immunol, Dept Med, 1720 2nd Ave South, Birmingham, AL 35294 USA.; Saag, KG (reprint author), Univ Alabama Birmingham, Div Rheumatol, Dept Med, 1720 2nd Ave South, Birmingham, AL 35294 USA. EM Ksaag@uab.edu FU Takeda Pharmaceuticals FX Under the direction of the authors, Meryl Gersh of AlphaBioCom provided writing, editing, and formatting assistance; this work was funded by Takeda Pharmaceuticals. NR 24 TC 4 Z9 5 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD AUG PY 2016 VL 68 IS 8 BP 2035 EP 2043 DI 10.1002/art.39654 PG 9 WC Rheumatology SC Rheumatology GA DW2UX UT WOS:000383498400028 PM 26894653 ER PT J AU Castillo, JJ Kanan, S Meid, K Manning, R Hunter, ZR Treon, SP AF Castillo, Jorge J. Kanan, Sandra Meid, Kirsten Manning, Robert Hunter, Zachary R. Treon, Steven P. TI Rituximab intolerance in patients with Waldenstrom macroglobulinaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Letter DE Waldenstrom macroglobulinaemia; Lymphoplasmacytic lymphoma; rituximab; infusion ID FOLLICULAR LYMPHOMA; 1ST-LINE TREATMENT; PLUS RITUXIMAB; OPEN-LABEL; TRIAL; PHASE-3; FLUDARABINE; THERAPY C1 [Castillo, Jorge J.; Kanan, Sandra; Meid, Kirsten; Manning, Robert; Hunter, Zachary R.; Treon, Steven P.] Dana Farber Canc Inst, Bing Ctr Waldenstrom Macroglobulinemia, Boston, MA 02115 USA. [Castillo, Jorge J.; Treon, Steven P.] Harvard Med Sch, Boston, MA 02115 USA. RP Castillo, JJ (reprint author), Dana Farber Canc Inst, Bing Ctr Waldenstrom Macroglobulinemia, Boston, MA 02115 USA.; Castillo, JJ (reprint author), Harvard Med Sch, Boston, MA 02115 USA. EM jorgej_castillo@dfci.harvard.edu OI Castillo, Jorge/0000-0001-9490-7532; Hunter, Zachary/0000-0002-1689-1691 NR 10 TC 4 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD AUG PY 2016 VL 174 IS 4 BP 645 EP 648 DI 10.1111/bjh.13794 PG 5 WC Hematology SC Hematology GA DW6PX UT WOS:000383774500020 PM 26523929 ER PT J AU Finn, JP Nguyen, KL Han, F Zhou, Z Salusky, I Ayad, I Hu, P AF Finn, J. P. Nguyen, K. -L. Han, F. Zhou, Z. Salusky, I. Ayad, I. Hu, P. TI Cardiovascular MRI with ferumoxytol SO CLINICAL RADIOLOGY LA English DT Review ID SUPERPARAMAGNETIC IRON-OXIDE; MAGNETIC-RESONANCE ANGIOGRAPHY; ACUTE KIDNEY INJURY; AORTIC-VALVE IMPLANTATION; NEPHROGENIC SYSTEMIC FIBROSIS; ACUTE MYOCARDIAL-INFARCTION; CONGENITAL HEART-DISEASE; BLOOD-POOL AGENT; CONTRAST AGENT; SPATIAL-RESOLUTION AB The practice of contrast-enhanced magnetic resonance angiography (CEMRA) has changed significantly in the span of a decade. Concerns regarding gadolinium (Gd)-associated nephrogenic systemic fibrosis in those with severely impaired renal function spurred developments in low-dose CEMRA and non-contrast MRA as well as efforts to seek alternative MR contrast agents. Originally developed for MR imaging use, ferumoxytol (an ultra-small superparamagnetic iron oxide nanoparticle), is currently approved by the US Food and Drug Administration for the treatment of iron deficiency anaemia in adults with renal disease. Since its clinical availability in 2009, there has been rising interest in the scientific and clinical use of ferumoxytol as an MR contrast agent. The unique physicochemical and pharmacokinetic properties of ferumoxytol, including its long intravascular half-life and high r(1) relaxivity, support a spectrum of MRI applications beyond the scope of Gd-based contrast agents. Moreover, whereas Gd is not found in biological systems, iron is essential for normal metabolism, and nutritional iron deficiency poses major public health challenges worldwide. Once the carbohydrate shell of ferumoxytol is degraded, the elemental iron at its core is incorporated into the reticuloendothelial system. These considerations position ferumoxytol as a potential game changer in the field of CEMRA and MRI. In this paper, we aim to summarise our experience with the cardiovascular applications of ferumoxytol and provide a brief synopsis of ongoing investigations on ferumoxytol-enhanced MR applications. (C) 2016 Published by Elsevier Ltd on behalf of The Royal College of Radiologists. C1 [Finn, J. P.; Nguyen, K. -L.; Han, F.; Zhou, Z.; Salusky, I.; Ayad, I.; Hu, P.] Univ Calif Los Angeles, David Geffen Sch Med, Diagnost Cardiovasc Imaging Lab, Los Angeles, CA 90095 USA. [Finn, J. P.; Han, F.; Zhou, Z.; Hu, P.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol Sci, Los Angeles, CA 90095 USA. [Nguyen, K. -L.] Univ Calif Los Angeles, David Geffen Sch Med, Div Cardiol, Los Angeles, CA 90095 USA. [Nguyen, K. -L.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Salusky, I.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Anesthesiol, Los Angeles, CA 90095 USA. [Salusky, I.] Univ Calif Los Angeles, David Geffen Sch Med, Div Pediat Nephrol, Los Angeles, CA 90095 USA. RP Finn, JP (reprint author), Univ Calif Los Angeles, Dept Radiol Sci, Peter V Ueberroth Bldg Suite 3371, Los Angeles, CA 90095 USA. EM pfinn@mednet.ucla.edu OI Nguyen, Kim-Lien/0000-0002-8854-2976 FU National Heart, Lung, and Blood Institute [R01HL127153] FX This work is supported by grant R01HL127153 from the National Heart, Lung, and Blood Institute. NR 65 TC 2 Z9 2 U1 2 U2 3 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0009-9260 EI 1365-229X J9 CLIN RADIOL JI Clin. Radiol. PD AUG PY 2016 VL 71 IS 8 SI SI BP 796 EP 806 DI 10.1016/j.crad.2016.03.020 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DW0ST UT WOS:000383353400009 PM 27221526 ER PT J AU Tiffany, E Wilder, CM Miller, SC Winhusen, T AF Tiffany, Elizabeth Wilder, Christine M. Miller, Shannon C. Winhusen, Theresa TI Knowledge of and interest in opioid overdose education and naloxone distribution among US veterans on chronic opioids for addiction or pain SO DRUGS-EDUCATION PREVENTION AND POLICY LA English DT Article DE Education; harm reduction; methadone; naloxone; opiate; opiates; opiate use; risk ID TAKE-HOME NALOXONE; NONFATAL HEROIN OVERDOSE; INJECTION-DRUG USERS; FRANCISCO BAY AREA; UNITED-STATES; INTRAMUSCULAR NALOXONE; SCREENING-TEST; PREVENTION; INTRANASAL; MANAGEMENT AB Aims: The Veterans Health Administration (VHA) is implementing opioid overdose (OOD) education and naloxone distribution to reduce rising rates of OOD deaths. This study assessed knowledge and interest in OOD prevention with naloxone at a VHA hospital where naloxone kits were not yet available. Methods: Veterans receiving opioids for 3 months, including 52 from the Opioid Substitution Clinic (OSC) and 38 from the Pain Management Clinic (PMC), were interviewed about their attitudes and experience with OOD and naloxone. Findings: 52% of OSC and 21% of PMC veterans reported having ever experienced an OOD. Less than half had heard of naloxone and none owned a naloxone kit. After a brief explanation, 73% of OSC and 55% of PMC veterans reported wanting a kit. Veterans who reported wanting a kit were more likely to have witnessed (p<0.001) and/or experienced (p<0.001) an OOD and were more likely to have used intravenous drugs in their lifetimes (p<0.05). Conclusions: Participants were not well informed about naloxone but many OSC veterans had a history of OOD and were interested in having a naloxone kit. There was also a subgroup of veterans prescribed opioids for chronic pain who had a history of OOD and were interested in naloxone. C1 [Tiffany, Elizabeth; Wilder, Christine M.; Miller, Shannon C.; Winhusen, Theresa] Univ Cincinnati, Dept Psychiat & Behav Neurosci, Coll Med, 260 Stetson St 3200, Cincinnati, OH 45219 USA. [Wilder, Christine M.; Miller, Shannon C.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. RP Tiffany, E (reprint author), Univ Cincinnati, Dept Psychiat & Behav Neurosci, Coll Med, 260 Stetson St 3200, Cincinnati, OH 45219 USA. EM kraftem@ucmail.uc.edu FU Department of Veterans Affairs; Research in Addiction Medicine Scholars (RAMS) Program, National Institute on Drug Abuse [R25DA033211] FX This report is based upon work supported by the Department of Veterans Affairs and the Research in Addiction Medicine Scholars (RAMS) Program, National Institute on Drug Abuse Award Number R25DA033211. NR 42 TC 1 Z9 1 U1 4 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 0968-7637 EI 1465-3370 J9 DRUG-EDUC PREV POLIC JI Drug-Educ. Prev. Policy PD AUG PY 2016 VL 23 IS 4 BP 322 EP 327 DI 10.3109/09687637.2015.1106442 PG 6 WC Substance Abuse SC Substance Abuse GA DW8CU UT WOS:000383881700007 ER PT J AU Kataoka, A Scherrer-Crosbie, M Senior, R Garceau, P Valbuena, S Celutkiene, J Hastings, JL Cheema, AN Lara, A Srbinovska-Kostovska, E Hessian, R Poggio, D Goldweit, R Saric, M Dajani, KA Kohn, JA Shaw, LJ Reynolds, HR Picard, MH AF Kataoka, Akihisa Scherrer-Crosbie, Marielle Senior, Roxy Garceau, Patrick Valbuena, Silvia Celutkiene, Jelena Hastings, Jeffrey L. Cheema, Asim N. Lara, Alfonso Srbinovska-Kostovska, Elizabeta Hessian, Renee Poggio, Daniele Goldweit, Richard Saric, Muhamed Dajani, Khaled A. Kohn, Jeffrey A. Shaw, Leslee J. Reynolds, Harmony R. Picard, Michael H. TI Transient Ischemic Dilatation during Stress Echocardiography: An Additional Marker of Significant Myocardial Ischemia SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Article DE stress echocardiography; myocardial ischemia; coronary artery disease ID CORONARY-ARTERY-DISEASE; VENTRICULAR CAVITY DILATION; CARDIAC RESYNCHRONIZATION; PROGNOSTIC IMPORTANCE; TL-201 SCINTIGRAPHY; HEART; VOLUME; TRIAL AB AimLeft ventricular (LV) transient ischemic dilatation (TID) is not clear how it relates to inducible myocardial ischemia during stress echocardiography (SE). Methods and ResultsEighty-eight SEs were examined from the site certification phase of the ISCHEMIA Trial. LV end-diastolic volume (EDV) and end-systolic volume (ESV) were measured at rest and peak stages and the percent change calculated. Moderate or greater ischemia was defined as 3 segments with stress-induced severe hypokinesis or akinesis. Optimum cut points in stress-induced percent EDV and ESV change that identified moderate or greater myocardial ischemia were analyzed. Analysis from percentage distribution identified a > 13% LV volume increase in EDV or a > 9% LV volume increase in ESV as the optimum cutoff points for moderate or greater ischemia. Using these definitions for TID, there were 27 (31%) with TIDESV and 12 (14%) with TIDEDV. By logistic regression analysis and receiver operating characteristic curves, the percent change in ESV had a stronger association with moderate or greater myocardial ischemia than that of EDV change. Compared to those without TIDESV, cases with TIDESV had larger extent of inducible wall-motion abnormalities, lower peak stress LVEF, and higher likelihood of moderate or grater ischemia. For moderate or greater myocardial ischemia detection, TIDESV had a sensitivity of 46%, specificity of 83%, positive predictive value of 70%, and negative predictive value of 64%. ConclusionTransient ischemic dilatation by SE is a marker of extensive myocardial ischemia and can be used as an additional marker of higher risk. C1 [Kataoka, Akihisa; Scherrer-Crosbie, Marielle; Picard, Michael H.] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 55 Fruit St,Yawkey 5E, Boston, MA 02114 USA. [Kataoka, Akihisa; Scherrer-Crosbie, Marielle; Picard, Michael H.] Harvard Med Sch, 55 Fruit St,Yawkey 5E, Boston, MA 02114 USA. [Senior, Roxy] Natl Heart & Lung Inst, Div Cardiol, Dept Cardiovasc Med, London, England. [Senior, Roxy] Imperial Coll, London, England. [Garceau, Patrick] Montreal Heart Inst, Dept Med, Montreal, PQ, Canada. [Valbuena, Silvia] La Paz Univ Hosp, Dept Cardiol, Madrid, Spain. [Celutkiene, Jelena] Vilnius Univ Hosp, Santariskiu Clin, Ctr Cardiol & Angiol, Vilnius, Lithuania. [Hastings, Jeffrey L.] VN Texas Hlth Care Syst, Div Cardiol, Dallas, TX USA. [Cheema, Asim N.] St Michaels Hosp, Div Cardiol, Toronto, ON, Canada. [Lara, Alfonso] La Raza Natl Med Ctr, Specialty Hosp, Dept Med, Mexico City, DF, Mexico. [Srbinovska-Kostovska, Elizabeta] Univ Clin Cardiol, Dept Internal Med, Skopje, Macedonia. [Hessian, Renee] Univ Ottawa, Inst Heart, Div Cardiol, Dept Med, Ottawa, ON, Canada. [Poggio, Daniele] Monza Polyclin, Div Cardiol, Dept Med, Monza, Italy. [Goldweit, Richard] Englewood Hosp & Med Ctr, Div Cardiol, Dept Med, Englewood, NJ USA. [Saric, Muhamed] NYU, Dept Med, Div Cardiol, Med Ctr, 550 1St Ave, New York, NY 10016 USA. [Dajani, Khaled A.] Loyola Univ, Med Ctr, Dept Med, Div Cardiol, Maywood, IL 60153 USA. [Kohn, Jeffrey A.] New York Med Associates, Dept Med, New York, NY USA. [Shaw, Leslee J.] Emory Univ, Sch Med, Dept Med, Div Cardiol, Atlanta, GA USA. [Reynolds, Harmony R.] NYU, Dept Med, Div Cardiol, Langone Med Ctr, 550 1St Ave, New York, NY 10016 USA. RP Picard, MH (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 55 Fruit St,Yawkey 5E, Boston, MA 02114 USA.; Picard, MH (reprint author), Harvard Med Sch, 55 Fruit St,Yawkey 5E, Boston, MA 02114 USA. EM mhpicard@mgh.harvard.edu OI Picard, Michael/0000-0002-9264-3243; Saric, Muhamed/0000-0001-7682-3749 FU Japanese Society of Echocardiography Overseas Research Fellowship; Uehara Memorial Foundation Research Fellowship; National Heart, Lung, and Blood Institute [5U01HL105561-02, 1U01HL10556-01] FX We thank Dr. Zeng Xin, Dr. Yong Hyun Park, Ms. Dana Oliver for their assistance in this project. This work was supported by grants from the Japanese Society of Echocardiography Overseas Research Fellowship and Uehara Memorial Foundation Research Fellowship (Dr. Kataoka), and the National Heart, Lung, and Blood Institute (5U01HL105561-02, 1U01HL10556-01). NR 22 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0742-2822 EI 1540-8175 J9 ECHOCARDIOGR-J CARD JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech. PD AUG PY 2016 VL 33 IS 8 BP 1202 EP 1208 DI 10.1111/echo.13222 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW0TF UT WOS:000383354900010 PM 27040889 ER PT J AU Malhotra, R Bakken, K D'Elia, E Lewis, GD AF Malhotra, Rajeev Bakken, Kristian D'Elia, Emilia Lewis, Gregory D. TI Cardiopulmonary Exercise Testing in Heart Failure SO JACC-HEART FAILURE LA English DT Article DE cardiopulmonary exercise testing; exercise physiology; heart failure; oxygen uptake; ventilatory efficiency ID PRESERVED EJECTION FRACTION; PEAK OXYGEN-CONSUMPTION; GAS-EXCHANGE; OSCILLATORY VENTILATION; CARDIAC RESYNCHRONIZATION; PROGNOSTIC IMPORTANCE; SUBMAXIMAL EXERCISE; AMBULATORY PATIENTS; CONTROLLED-TRIAL; EFFICIENCY AB Exercise intolerance, indicated by dyspnea and fatigue during exertion, is a cardinal manifestation of heart failure (HF). Cardiopulmonary exercise testing (CPET) precisely defines maximum exercise capacity through measurement of peak oxygen uptake (VO2). Peak VO2 values have a critical role in informing patient selection for advanced HF interventions such as heart transplantation and ventricular assist devices. Oxygen uptake and ventilatory patterns obtained during the submaximal portion of CPET are also valuable to recognize because of their ease of ascertainment during low-level exercise, relevance to ability to perform activities of daily living, independence from volitional effort, and strong relationship to prognosis in HF. The ability of peak VO2 and other CPET variables to be measured reproducibly and to accurately reflect HF severity is increasingly recognized and endorsed by scientific statements. Integration of CPET with invasive hemodynamic monitoring and cardiac imaging during exercise provides comprehensive characterization of multisystem reserve capacity that can inform prognosis and the need for cardiac interventions. Here, we review both practical aspects of conducting CPETs in patients with HF for clinical and research purposes as well as interpretation of gas exchange patterns across the spectrum of preclinical HF to advanced HF. (C) 2016 by the American College of Cardiology Foundation. C1 [Malhotra, Rajeev; Lewis, Gregory D.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA USA. [Bakken, Kristian; Lewis, Gregory D.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA USA. [D'Elia, Emilia] Hosp Papa Giovanni XXIII, Cardiovasc Dept, Bergamo, Italy. [D'Elia, Emilia] Univ Pavia, Pavia, Italy. RP Lewis, GD (reprint author), Massachusetts Gen Hosp, Heart Failure & Cardiac Transplantat Unit, Bigelow 800,55 Fruit St, Boston, MA 02114 USA. EM glewis@partners.org OI Malhotra, Rajeev/0000-0003-0120-4630 FU NHLBI NIH HHS [K08 HL111210] NR 66 TC 4 Z9 4 U1 9 U2 9 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 AUG PY 2016 VL 4 IS 8 BP 607 EP 616 DI 10.1016/j.jchf.2016.03.022 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW1ME UT WOS:000383406500001 PM 27289406 ER PT J AU Schlosser, RJ Mulligan, JK Hyer, JM Karnezis, TT Gudis, DA Soler, ZM AF Schlosser, Rodney J. Mulligan, Jennifer K. Hyer, J. Madison Karnezis, Tom T. Gudis, David A. Soler, Zachary M. TI Mucous Cytokine Levels in Chronic Rhinosinusitis-Associated Olfactory Loss SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID ENDOSCOPIC SINUS SURGERY; NECROSIS-FACTOR-ALPHA; NASAL POLYPS; IDENTIFICATION; INTERLEUKIN-6; MODEL AB IMPORTANCE Olfactory loss is a frequent symptom of patients with chronic rhinosinusitis (CRS), but our understanding of how inflammatory cytokines affect olfaction is limited. OBJECTIVES To examine whether inflammatory cytokines are present in the olfactory cleft and whether they correlate with objective olfaction. DESIGN, SETTING, AND PARTICIPANTS In this cross-sectional study, patients with CRS underwent quantitative olfactory testing using the Sniffin Sticks test to calculate a composite threshold discrimination identification (TDI) score from October 21, 2013, to November 12, 2015. Nasal mucus was collected using a sponge placed in the olfactory cleft for 5 minutes, and Cytometric Bead Array was used to measure secreted immunomodulatory products. Correlations between TDI score and secreted mediators were then calculated. Data analysis was performed from October 15, 2015, to December 17, 2015. MAIN OUTCOMES AND MEASURES Composite TDI scores and mean secreted mediator levels in mucus from the olfactory cleft. RESULTS Thirty-four patients were enrolled (mean [SD] age, 57.3 [15.7] years; female, 21 [61.8%]; white, 26 [76.5]). The TDI scores were lower in patients with CRS with nasal polyps (CRSwNP) than in patients with CRS without nasal polyps (CRSsNP) (difference, 8.7; 95% CI, 2.5-15.0; P = .007). Interleukin (IL) 5 levels were inversely correlated with TDI scores in patients with CRSwNP and those with CRSsNP (mean [SE] beta estimate, -46.56 [15.11]; P = .005), whereas IL-6, IL-7, and vascular endothelial growth factor A were positively correlated with TDI scores only in the CRSwNP cohort. Subscale olfactory TDI scores followed similar correlations to composite TDI scores. CONCLUSIONS AND RELEVANCE In this study, inflammatory cytokines were found in mucus collected from the olfactory cleft. Levels of IL-5, in addition to other cytokines, were associated with objective olfactory function. Further inquiry is needed to establish the source of mucous cytokines and establish whether they play a causal role in olfactory loss. C1 [Schlosser, Rodney J.; Mulligan, Jennifer K.; Karnezis, Tom T.; Gudis, David A.; Soler, Zachary M.] Med Univ South Carolina, Dept Otolaryngol Head & Neck Surg, 135 Rutledge Ave,Mail Stop Code 550, Charleston, SC 29425 USA. [Schlosser, Rodney J.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Mulligan, Jennifer K.] Med Univ South Carolina, Dept Pediat, Charleston, SC 29425 USA. [Hyer, J. Madison] Med Univ South Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. RP Soler, ZM (reprint author), Med Univ South Carolina, Dept Otolaryngol Head & Neck Surg, 135 Rutledge Ave,Mail Stop Code 550, Charleston, SC 29425 USA. EM solerz@musc.edu FU National Institute on Deafness and Other Communication Disorders [R03 DC013651-01]; OptiNose; IntersectENT FX All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Schlosser reported receiving grant support from OptiNose and IntersectENT and working as a consultant for Olympus and Meda. Dr Soler reported receiving support from grant R03 DC013651-01 from the National Institute on Deafness and Other Communication Disorders and working as a consultant for Olympus. No other disclosures were reported. NR 23 TC 2 Z9 2 U1 2 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 AUG PY 2016 VL 142 IS 8 BP 731 EP 737 DI 10.1001/jamaoto.2016.0927 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA DW6PS UT WOS:000383774000003 PM 27228459 ER PT J AU Storch, EA Wilhelm, S Sprich, S Henin, A Micco, J Small, BJ McGuire, J Mutch, J Lewin, AB Murphy, TK Geller, DA AF Storch, Eric A. Wilhelm, Sabine Sprich, Susan Henin, Aude Micco, Jamie Small, Brent J. McGuire, Joseph Mutch, Jane Lewin, Adam B. Murphy, Tanya K. Geller, Daniel A. TI Efficacy of Augmentation of Cognitive Behavior Therapy With Weight-Adjusted D-Cycloserine vs Placebo in Pediatric Obsessive-Compulsive Disorder A Randomized Clinical Trial SO JAMA PSYCHIATRY LA English DT Article ID SOCIAL ANXIETY DISORDER; POSTTRAUMATIC-STRESS-DISORDER; EXPOSURE THERAPY; FEAR EXTINCTION; TREATMENT RESPONSE; OCD TREATMENT; CHILDREN; SCALE; ENHANCEMENT; RELIABILITY AB IMPORTANCE Cognitive behavior therapy (CBT) among youth with obsessive-compulsive disorder (OCD) is effective, but many patients remain symptomatic after intervention. D-cycloserine, a partial agonist at the N-methyl-D-aspartate receptor in the amygdala, has been associated with enhanced CBT outcome for OCD among adults but requires evaluation among youth. OBJECTIVES To examine the relative efficacy of weight-adjusted D-cycloserine (25 or 50mg) vs placebo augmentation of CBT for youth with OCD and to assess if concomitant antidepressant medication moderated effects. DESIGN, SETTING, AND PARTICIPANTS In a placebo-controlled randomized clinical trial, 142 youths (age range, 7-17 years) enrolled between June 1, 2011, and January 30, 2015, at 2 academic health science centers (University of South Florida and Massachusetts General Hospital) with a primary diagnosis of OCD were randomized in a double-blind fashion to D-cycloserine plus CBT or placebo plus CBT. Intent-to-treat analysis was performed. INTERVENTIONS Patients were randomly assigned in a 1: 1 ratio to either 10 sessions of D-cycloserine plus CBT or placebo plus CBT. D-cycloserine (25 or 50mg) or placebo was taken 1 hour before sessions 4 through 10. MAIN OUTCOMES AND MEASURES Children's Yale-Brown Obsessive Compulsive Scale at randomization, biweekly, midtreatment, and posttreatment. Secondary outcomes included the Clinical Global Impressions-Severity or Clinical Global Impressions-Improvement, remission status, Children's Depression Rating Scale, Multidimensional Anxiety Scale for Children, and Children's Obsessive-Compulsive Impact Scale-Parent Version. RESULTS The study cohort comprised 142 participants. Their mean (SD) age was 12.7 (2.9) years, and 53.5%(76 of 142) were female. A mixed-effects model using all available data indicated significant declines in the Children's Yale-Brown Obsessive Compulsive Scale total score and Clinical Global Impressions-Severity. No significant interaction between treatment group and changes in the Children's Yale-Brown Obsessive Compulsive Scale and Clinical Global Impressions-Severity indicated that the D-cycloserine plus CBT group and the placebo plus CBT group declined at similar rates per assessment point on the Children's Yale-Brown Obsessive Compulsive Scale total score (estimate, -2.31, 95% CI, -2.79 to -1.83 and estimate, -2.03, 95% CI, -2.47 to -1.58, respectively) and Clinical Global Impressions-Severity (estimate, -0.29, 95% CI, -0.35 to -0.22 and estimate, -0.23, 95% CI, -0.29 to -0.17, respectively). No group differences in secondary outcomes were present. Antidepressant medication use at baseline did not moderate changes for either group. CONCLUSIONS AND RELEVANCE D-cycloserine augmentation of CBT did not confer additional benefit relative to placebo among youth with OCD. Other augmentation approaches should be examined to enhance outcome. C1 [Storch, Eric A.; Mutch, Jane; Lewin, Adam B.; Murphy, Tanya K.] Univ S Florida, Dept Pediat, Tampa, FL USA. [Storch, Eric A.] Univ S Florida, Dept Hlth Policy & Management, Tampa, FL USA. [Storch, Eric A.; Lewin, Adam B.; Murphy, Tanya K.] Univ S Florida, Dept Psychiat & Behav Neurosci, Tampa, FL USA. [Storch, Eric A.] Rogers Behav Hlth Tampa Bay, Tampa, FL USA. [Storch, Eric A.; Murphy, Tanya K.] Johns Hopkins All Childrens Hosp, St Petersburg, FL USA. [Wilhelm, Sabine; Sprich, Susan; Henin, Aude; Micco, Jamie; Geller, Daniel A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Wilhelm, Sabine; Sprich, Susan; Henin, Aude; Micco, Jamie; Geller, Daniel A.] Harvard Med Sch, Dept Psychiat, Boston, MA USA. [Small, Brent J.] Univ S Florida, Sch Aging Studies, Tampa, FL USA. [McGuire, Joseph] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. RP Storch, EA (reprint author), Univ S Florida, Dept Pediat, 880 Sixth St S,POB 7523, St Petersburg, FL 33701 USA. EM estorch@health.usf.edu FU National Institute of Mental Health [1R01MH093381, 5R01MH093402] FX This work was supported by grants 1R01MH093381 (Dr Storch) and 5R01MH093402 (Dr Geller) from the National Institute of Mental Health. NR 47 TC 4 Z9 4 U1 7 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD AUG PY 2016 VL 73 IS 8 BP 779 EP 788 DI 10.1001/jamapsychiatry.2016.1128 PG 10 WC Psychiatry SC Psychiatry GA DW9OX UT WOS:000383991700007 PM 27367832 ER PT J AU VanderWeele, TJ Li, SS Tsai, AC Kawachi, I AF VanderWeele, Tyler J. Li, Shanshan Tsai, Alexander C. Kawachi, Ichiro TI Association Between Religious Service Attendance and Lower Suicide Rates Among US Women SO JAMA PSYCHIATRY LA English DT Article ID NATIONALLY REPRESENTATIVE SAMPLE; SOCIAL INTEGRATION; SENSITIVITY-ANALYSIS; AFRICAN-AMERICANS; UNITED-STATES; BEHAVIOR; DEPRESSION; MORTALITY; IDEATION; COHORT AB IMPORTANCE Previous studies have linked suicide risk with religious participation, but the majority have used ecologic, cross-sectional, or case-control data. OBJECTIVE To examine the longitudinal association between religious service attendance and suicide and the joint associations of suicide with service attendance and religious affiliation. DESIGN, SETTING, AND PARTICIPANTS We evaluated associations between religious service attendance and suicide from 1996 through June 2010 in a large, long-term prospective cohort, the Nurses' Health Study, in an analysis that included 89 708 women. Religious service attendance was self-reported in 1992 and 1996. Data analysis was conducted from 1996 through 2010. MAIN OUTCOMES AND MEASURES Cox proportional hazards regression models were used to examine the association between religious service attendance and suicide, adjusting for demographic covariates, lifestyle factors, medical history, depressive symptoms, and social integration measures. We performed sensitivity analyses to examine the influence of unmeasured confounding. RESULTS Among 89 708 women aged 30 to 55 years who participated in the Nurses' Health Study, attendance at religious services once per week or more was associated with an approximately 5-fold lower rate of suicide compared with never attending religious services (hazard ratio, 0.16; 95% CI, 0.06-0.46). Service attendance once or more per week vs less frequent attendance was associated with a hazard ratio of 0.05 (95% CI, 0.006-0.48) for Catholics but only 0.34 (95% CI, 0.10-1.10) for Protestants (P = .05 for heterogeneity). Results were robust in sensitivity analysis and to exclusions of persons who were previously depressed or had a history of cancer or cardiovascular disease. There was evidence that social integration, depressive symptoms, and alcohol consumption partially mediated the association among those occasionally attending services, but not for those attending frequently. CONCLUSIONS AND RELEVANCE In this cohort of US women, frequent religious service attendance was associated with a significantly lower rate of suicide. C1 [VanderWeele, Tyler J.; Li, Shanshan] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave,Kresge Bldg, Boston, MA 02115 USA. [VanderWeele, Tyler J.] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [VanderWeele, Tyler J.] Harvard Univ, Inst Quantitat Social Sci, Program Integrat Knowledge & Human Flourishing, Cambridge, MA 02138 USA. [Tsai, Alexander C.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Tsai, Alexander C.] Harvard Ctr Populat & Dev Studies, Cambridge, MA USA. [Tsai, Alexander C.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Kawachi, Ichiro] Harvard TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA USA. RP VanderWeele, TJ (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave,Kresge Bldg, Boston, MA 02115 USA. EM tvanderw@hsph.harvard.edu FU National Institutes of Health [UM1 CA186107]; Templeton Foundation FX The Nurses' Health Study was funded by grant UM1 CA186107 from the National Institutes of Health. The analysis and paper was supported by a research grant from the Templeton Foundation. NR 36 TC 7 Z9 7 U1 10 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD AUG PY 2016 VL 73 IS 8 BP 845 EP 851 DI 10.1001/jamapsychiatry.2016.1243 PG 7 WC Psychiatry SC Psychiatry GA DW9OX UT WOS:000383991700014 PM 27367927 ER PT J AU Lilley, EJ Cauley, CE Cooper, Z AF Lilley, Elizabeth J. Cauley, Christy E. Cooper, Zara TI Using a Palliative Care Framework for Seriously Ill Surgical Patients The Example of Malignant Bowel Obstruction SO JAMA SURGERY LA English DT Editorial Material ID CARCINOMATOSIS C1 [Lilley, Elizabeth J.] Rutgers Robert Wood Johnson Med Sch, Dept Surg, Brunswick, NJ USA. [Lilley, Elizabeth J.; Cooper, Zara] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, One Brigham Circle,1620 Tremont St,Ste 4-020, Boston, MA 02120 USA. [Cauley, Christy E.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Cauley, Christy E.] Ariadne Labs, Boston, MA USA. [Cooper, Zara] Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. RP Lilley, EJ (reprint author), Brigham & Womens Hosp, Ctr Surg & Publ Hlth, One Brigham Circle,1620 Tremont St,Ste 4-020, Boston, MA 02120 USA. EM elilley@bwh.harvard.edu OI Lilley, Elizabeth/0000-0002-3617-9829 FU NCI NIH HHS [R25 CA092203] NR 7 TC 0 Z9 0 U1 1 U2 1 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 AUG PY 2016 VL 151 IS 8 BP 695 EP 696 DI 10.1001/jamasurg.2016.0057 PG 2 WC Surgery SC Surgery GA DW6QD UT WOS:000383775100005 PM 27096440 ER PT J AU Rosengart, TK Kent, KC Bland, KI Britt, LD Eberlein, TJ Gewertz, BL Hunter, JG Lillemoe, KD Pellegrini, CA Schulick, RD Stain, SC Weigel, RJ AF Rosengart, Todd K. Kent, K. Craig Bland, Kirby I. Britt, L. D. Eberlein, Timothy J. Gewertz, Bruce Labe Hunter, John G. Lillemoe, Keith D. Pellegrini, Carlos A. Schulick, Richard D. Stain, Steven Charles Weigel, Ronald J. TI Key Tenets of Effective Surgery Leadership Perspectives From the Society of Surgical Chairs Mentorship Sessions SO JAMA SURGERY LA English DT Review AB This Special Communication summarizes the key points raised at the Society of Surgical Chairs mentorship panel sessions held at the 2014 and 2015 annual meetings of the society. Highlights of these expert panel discussions include senior chairs' insights into successfully dealing with increasingly complex academic medical organizations and horizontal department management expectations in the context of the arrival of the Millennial Generation into the work force. Three key tenets of effective surgery leadership that arose from these sessions deal with the importance of (1) collaboration and cooperativity, (2) humanized relationships and mentorship, and (3) operational efficiency. Overall, the panel consensus for the future of surgery leadership was optimistic while recognizing that the demands of chairmanship are considerable. C1 [Rosengart, Todd K.] Baylor Coll Med, Houston, TX 77030 USA. [Kent, K. Craig] Univ Wisconsin, Sch Med, Madison, WI USA. [Bland, Kirby I.] Univ Alabama Birmingham, Birmingham, AL USA. [Britt, L. D.] Eastern Virginia Med Sch, Norfolk, VA 23501 USA. [Eberlein, Timothy J.] Washington Univ, Sch Med, St Louis, MO USA. [Gewertz, Bruce Labe] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Hunter, John G.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Lillemoe, Keith D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pellegrini, Carlos A.] Univ Washington, Seattle, WA 98195 USA. [Schulick, Richard D.] Univ Colorado, Anschutz Med Campus, Aurora, CO USA. [Stain, Steven Charles] Albany Med Coll, Albany, NY 12208 USA. [Weigel, Ronald J.] Univ Iowa, Coll Med, Iowa City, IA USA. RP Rosengart, TK (reprint author), Baylor Coll Med, Michael E DeBakey Dept Surg, 1 Baylor Plz, Houston, TX 77030 USA. EM todd.rosengart@bcm.edu NR 7 TC 0 Z9 0 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD AUG PY 2016 VL 151 IS 8 BP 768 EP 770 DI 10.1001/jamasurg.2016.0405 PG 3 WC Surgery SC Surgery GA DW6QD UT WOS:000383775100020 PM 27096328 ER PT J AU Minami, CA Dahlke, AR Barnard, C Kinnier, CV Rajaram, RR Noskin, GA Bilimoria, KY AF Minami, Christina A. Dahlke, Allison R. Barnard, Cynthia Kinnier, Christine V. Rajaram, Ravi R. Noskin, Gary A. Bilimoria, Karl Y. TI Association Between Hospital Characteristics and Performance on the New Hospital-Acquired Condition Reduction Program's Surgical Site Infection Measures SO JAMA SURGERY LA English DT Letter C1 [Minami, Christina A.; Dahlke, Allison R.; Rajaram, Ravi R.; Bilimoria, Karl Y.] Northwestern Univ, Surg Outcomes & Qual Improvement Ctr, Dept Surg, Feinberg Sch Med, 633 N St Clair,20th Floor, Chicago, IL 60611 USA. [Minami, Christina A.; Dahlke, Allison R.; Rajaram, Ravi R.; Bilimoria, Karl Y.] Northwestern Univ, Ctr Healthcare Studies, Feinberg Sch Med, Chicago, IL 60611 USA. [Barnard, Cynthia] Northwestern Mem HealthCare, Div Qual, Chicago, IL USA. [Kinnier, Christine V.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Noskin, Gary A.] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Dept Med, Chicago, IL 60611 USA. RP Bilimoria, KY (reprint author), Northwestern Univ, Surg Outcomes & Qual Improvement Ctr, Dept Surg, Feinberg Sch Med, 633 N St Clair,20th Floor, Chicago, IL 60611 USA. EM k-bilimoria@northwestern.edu NR 5 TC 1 Z9 1 U1 1 U2 1 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 AUG PY 2016 VL 151 IS 8 BP 777 EP 779 DI 10.1001/jamasurg.2016.0408 PG 3 WC Surgery SC Surgery GA DW6QD UT WOS:000383775100024 PM 27050254 ER PT J AU Robinaugh, DJ Millner, AJ McNally, RJ AF Robinaugh, Donald J. Millner, Alexander J. McNally, Richard J. TI Identifying Highly Influential Nodes in the Complicated Grief Network SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE network analysis; centrality; complicated grief; expected influence; persistent complex bereavement disorder ID BEREAVEMENT; CENTRALITY; DISORDER; TRIAL; MODEL AB The network approach to psychopathology conceptualizes mental disorders as networks of mutually reinforcing nodes (i.e., symptoms). Researchers adopting this approach have suggested that network topology can be used to identify influential nodes, with nodes central to the network having the greatest influence on the development and maintenance of the disorder. However, because commonly used centrality indices do not distinguish between positive and negative edges, they may not adequately assess the nature and strength of a node's influence within the network. To address this limitation, we developed 2 indices of a node's expected influence (EI) that account for the presence of negative edges. To evaluate centrality and EI indices, we simulated single-node interventions on randomly generated networks. In networks with exclusively positive edges, centrality and EI were both strongly associated with observed node influence. In networks with negative edges, EI was more strongly associated with observed influence than was centrality. We then used data from a longitudinal study of bereavement to examine the association between (a) a node's centrality and EI in the complicated grief (CG) network and (b) the strength of association between change in that node and change in the remainder of the CG network from 6- to 18-months postloss. Centrality and EI were both correlated with the strength of the association between node change and network change. Together, these findings suggest high-EI nodes, such as emotional pain and feelings of emptiness, may be especially important to the etiology and treatment of CG. C1 [Robinaugh, Donald J.] Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,Room 644, Boston, MA 02114 USA. [Robinaugh, Donald J.] Harvard Med Sch, Boston, MA USA. [Millner, Alexander J.; McNally, Richard J.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Robinaugh, DJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,Room 644, Boston, MA 02114 USA. EM drobinaugh@partners.org FU Nancy Pritzker Research Network; National Institute of Aging [AG15948-01, AG610757-01, AG05561-01] FX The Changing Lives of Older Couples study was supported by grants from the Nancy Pritzker Research Network and the National Institute of Aging (Grants AG15948-01; AG610757-01; AG05561-01). We thank Sacha Epskamp, Eiko Fried, Susanne Hoeppner, Robin Mankel, and two anonymous reviewers for their helpful feedback on earlier drafts of this article. NR 28 TC 1 Z9 1 U1 1 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X EI 1939-1846 J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD AUG PY 2016 VL 125 IS 6 BP 747 EP 757 DI 10.1037/abn0000181 PG 11 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA DV6PN UT WOS:000383059200001 PM 27505622 ER PT J AU Aaron, SE Gregory, CM Simpson, AN AF Aaron, Stacey E. Gregory, Chris M. Simpson, Annie N. TI Lower Odds of Poststroke Symptoms of Depression When Physical Activity Guidelines Met: National Health and Nutrition Examination Survey 2011-2012 SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH LA English DT Article DE Patient Health Questionnaire-9; Global Physical Activity Questionnaire; MET-minute/week ID QUALITY-OF-LIFE; ANTIDEPRESSANT THERAPY; FUNCTIONAL RECOVERY; STROKE PATIENTS; POST STROKE; ADULTS; EXERCISE; METAANALYSIS; ASSOCIATION; DISORDERS AB Background: One-third of individuals with stroke report symptoms of depression, which has a negative impact on recovery. Physical activity (PA) is a potentially effective therapy. Our objective was to examine the associations of subjectively assessed PA levels and symptoms of depression in a nationally representative stroke sample. Methods: We conducted a cross-sectional study of 175 adults in the National Health and Nutrition Examination Survey 2011-2012 cycle. Moderate, vigorous, and combination equivalent PA metabolic equivalent (MET)-minutes per week averages were derived from the Global Physical Activity Questionnaire, and the 2008 Physical Activity Guidelines/American College of Sports Medicine recommendations of >= 500 MET -minutes per week of moderate, vigorous, or combination equivalent PA were used as cut points. Depression symptoms were measured using the Patient Health Questionnaire-9. Results: Meeting moderate PA guidelines resulted in 74% lower odds of having depression symptoms (P < .0001) and 89% lower odds of major symptoms of depression (P = .0003). Meeting vigorous guidelines showed a 91% lower odds of having mild symptoms of depression (P = .04). Participating in some moderate, vigorous, or combination equivalent PA revealed the odds of depression symptoms 13 times greater compared with meeting guidelines (P = .005); odds of mild symptoms of depression were 9 times greater (P = .01); and odds of major symptoms of depression were 15 times greater (P = .006). Conclusions: There is a lower risk of developing mild symptoms of depression when vigorous guidelines for PA are met and developing major symptoms of depression when moderate guidelines met. Participating in some PA is not enough to reduce the risk of depression symptoms. C1 [Aaron, Stacey E.; Gregory, Chris M.] Med Univ South Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Gregory, Chris M.] Med Univ South Carolina, Div Phys Therapy, Charleston, SC USA. [Gregory, Chris M.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Simpson, Annie N.] Med Univ South Carolina, Dept Healthcare Leadership & Management, Charleston, SC USA. RP Aaron, SE (reprint author), Med Univ South Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. EM aarons@musc.edu FU NIGMS NIH HHS [P20 GM109040] NR 41 TC 0 Z9 0 U1 1 U2 1 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1543-3080 EI 1543-5474 J9 J PHYS ACT HEALTH JI J. Phys. Act. Health PD AUG PY 2016 VL 13 IS 8 BP 903 EP 909 DI 10.1123/jpah.2015-0446 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DW1OV UT WOS:000383413400014 PM 27145542 ER PT J AU Caragacianu, DL Mayer, EL Chun, YS Caterson, S Bellon, JR Wong, JS Troyan, S Rhei, E Dominici, LS Economy, KE Tung, NM Schapira, L Partridge, A Calvillo, KZ AF Caragacianu, Diana L. Mayer, Erica L. Chun, Yoon S. Caterson, Stephanie Bellon, Jennifer R. Wong, Julia S. Troyan, Susan Rhei, Esther Dominici, Laura S. Economy, Katherine E. Tung, Nadine M. Schapira, Lidia Partridge, Ann Calvillo, Katherina Zabicki TI Immediate Breast Reconstruction Following Mastectomy in Pregnant Women With Breast Cancer SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE pregnancy; malignancy; reconstructive surgery; fetal outcomes; multidisciplinary care ID SKIN-SPARING MASTECTOMY; RADIATION-THERAPY; SURGICAL OUTCOMES; POSTMASTECTOMY RECONSTRUCTION; IRRADIATED BREAST; RISK; RADIOTHERAPY; RECURRENCE; ANESTHESIA; IMPACT AB Background: Surgical management of breast cancer in pregnancy (BCP) requires balancing benefits of therapy with potential risks to the developing fetus. Minimal data describe outcomes after mastectomy with immediate breast reconstruction (IR) in pregnant patients. Methods: Retrospective review was performed of patients who underwent IR after mastectomy within a BCP cohort. Parameters included intraand post-operative complications, short-term maternal/fetal outcomes, surgery duration, and delayed reconstruction in non-IR cohort. Results: Of 82 patients with BCP, 29 (35%) had mastectomy during pregnancy: 10 (34%) had IR, 19(66%) did not. All IR utilized tissue expander (TE) placement. Mean gestational age (GA) at IR was 16.2 weeks. Mean surgery duration was 198 min with IR versus 157 min without IR. Those with IR delivered at, or close to, term infants of normal birthweight. No fetal or major obstetrical complications were seen. Post-mastectomy radiation (PMRT) was provided after pregnancy in 2 (20%) patients in the IR cohort and 12 (63%) in the non-IR cohort. All patients in the IR cohort successfully transitioned to permanent implant. Conclusions: This report represents one of the largest series describing IR during BCP. IR after mastectomy increased surgery duration, but was not associated with adverse obstetrical or fetal outcomes. IR with TE may preserve reconstructive options when PMRT is indicated. (C) 2016 Wiley Periodicals, Inc. C1 [Caragacianu, Diana L.; Mayer, Erica L.; Bellon, Jennifer R.; Wong, Julia S.; Troyan, Susan; Rhei, Esther; Dominici, Laura S.; Partridge, Ann; Calvillo, Katherina Zabicki] Dana Farber Brigham & Womens Canc Ctr, 450 Brookline Ave,Yawkey 14,Suite 1440, Boston, MA 02115 USA. [Chun, Yoon S.; Caterson, Stephanie; Economy, Katherine E.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Tung, Nadine M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Schapira, Lidia] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Calvillo, KZ (reprint author), Dana Farber Brigham & Womens Canc Ctr, 450 Brookline Ave,Yawkey 14,Suite 1440, Boston, MA 02115 USA. EM kzcalvillo@partners.org NR 43 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-4790 EI 1096-9098 J9 J SURG ONCOL JI J. Surg. Oncol. PD AUG 1 PY 2016 VL 114 IS 2 BP 140 EP 143 DI 10.1002/jso.24308 PG 4 WC Oncology; Surgery SC Oncology; Surgery GA DW6RQ UT WOS:000383779000002 PM 27392534 ER PT J AU Langerhuizen, DWG Janssen, SJ van der Vliet, QMJ Raskin, KA Ferrone, ML Hornicek, FJ Schwab, JH Lozano-Calderon, SA AF Langerhuizen, David W. G. Janssen, Stein J. van der Vliet, Quirine M. J. Raskin, Kevin A. Ferrone, Marco L. Hornicek, Francis J. Schwab, Joseph H. Lozano-Calderon, Santiago A. TI Metastasectomy, Intralesional Resection, or Stabilization Only in the Treatment of Bone Metastases From Renal Cell Carcinoma SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE bone metastasis; renal cell carcinoma; metastasectomy; intralesional curettage; resection ID SKELETAL METASTASES; OSSEOUS METASTASES; PATIENT SURVIVAL; SURGERY; KIDNEY AB Background: The mainstay of treatment for bone metastases from renal cell carcinoma is surgery. We assessed if there was a difference in local recurrence, reoperation, and survival between patients who underwent metastasectomy, intralesional curettage, or stabilization only for renal cell carcinoma metastasis to the appendicular skeleton, and if there was a difference in these outcomes based on margin status. Methods: This retrospective study included 183 patients; 48% underwent metastasectomy (n = 88, margins: 64 negative; 20 positive; 4 unclear), 30% intralesional curettage (n = 54), and 22% stabilization only (n = 41). Results: The recurrence rate differed and was highest after stabilization only (39%), followed by intralesional curettage (22%), and metastasectomy (12%) (P = 0.003). However, we found no difference in reoperation rate (P = 0.847). Survival was better in patients who underwent metastasectomy (P = 0.020). The recurrence rate was lower in patients who had a negative margin (5%) as compared to those with a positive margin (26%) (P< 0.001). However, we found no difference in reoperation rate (P = 0.97). Negative margins showed better survival (P< 0.001). Conclusions: Our findings emphasize the importance of obtaining negative margins in patients with a good life expectancy, as lower recurrence rate can be attained at a not significant additional risk for reoperation, with a potential impact on survival. (C) 2016 Wiley Periodicals, Inc. C1 [Langerhuizen, David W. G.; Janssen, Stein J.; van der Vliet, Quirine M. J.; Raskin, Kevin A.; Hornicek, Francis J.; Schwab, Joseph H.; Lozano-Calderon, Santiago A.] Harvard Med Sch, Massachusetts Gen Hosp, Orthopaed Oncol Serv, Dept Orthopaed Surg, Boston, MA USA. [Ferrone, Marco L.] Harvard Med Sch, Brigham & Womens Hosp, Orthopaed Oncol Serv, Dept Orthopaed Surg, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Janssen, SJ (reprint author), Massachusetts Gen Hosp, Orthopaed Surg, Room 3-946,Yawkey Bldg,55 Fruit St, Boston, MA 02114 USA. EM steinjanssen@gmail.com NR 23 TC 1 Z9 1 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-4790 EI 1096-9098 J9 J SURG ONCOL JI J. Surg. Oncol. PD AUG 1 PY 2016 VL 114 IS 2 BP 237 EP 245 DI 10.1002/jso.24284 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA DW6RQ UT WOS:000383779000018 PM 27156495 ER PT J AU Shera, CA Abdala, C AF Shera, Christopher A. Abdala, Carolina TI Frequency shifts in distortion-product otoacoustic emissions evoked by swept tones SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID BASILAR-MEMBRANE RESPONSES; SWEEPING PRIMARIES; FINE-STRUCTURE; INNER-EAR; DPOAE; NEWBORNS; DELAYS; ADULTS; DISPERSION; BREAKING AB When distortion-product otoacoustic emissions (DPOAEs) are evoked using stimuli whose instantaneous frequencies change rapidly and continuously with time (swept tones), the oscillatory interference pattern known as distortion-product fine structure shifts slightly along the frequency axis in the same direction as the sweep. By analogy with the temporal mechanisms thought to underlie the differing efficacies of up-and down-swept stimuli as perceptual maskers (e.g., Schroeder-phase complexes), fine-structure shifts have been ascribed to the phase distortion associated with dispersive wave propagation in the cochlea. This paper tests an alternative hypothesis and finds that the observed shifts arise predominantly as a methodological side effect of the analysis procedures commonly used to extract delayed emissions from the measured time waveform. Approximate expressions for the frequency shifts of DPOAE distortion and reflection components are derived, validated with computer simulations, and applied to account for DPOAE fine-structure shifts measured in human subjects. Component magnitudes are shown to shift twice as much as component phases. Procedures for compensating swept-tone measurements to obtain estimates of the total DPOAE and its components measured at other sweep rates or in the sinusoidal steady state are presented. (C) 2016 Acoustical Society of America. C1 [Shera, Christopher A.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. [Shera, Christopher A.; Abdala, Carolina] Univ Southern Calif, Keck Sch Med, Caruso Dept Otolaryngol, 1540 Alcazar St, Los Angeles, CA 90033 USA. RP Shera, CA (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA.; Shera, CA (reprint author), Univ Southern Calif, Keck Sch Med, Caruso Dept Otolaryngol, 1540 Alcazar St, Los Angeles, CA 90033 USA. EM christopher.shera@gmail.com FU NIH/NIDCD [R01 DC003687, R01 DC003552] FX The authors thank Karolina Charaziak and John Guinan for helpful comments on the manuscript and Ping Luo and Amanda Ortmann for help with subject testing and data analysis. Supported by NIH/NIDCD Grant Nos. R01 DC003687 (CAS) and R01 DC003552 (CA). NR 33 TC 0 Z9 0 U1 0 U2 0 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 AUG PY 2016 VL 140 IS 2 BP 936 EP 944 DI 10.1121/1.4960592 PG 9 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA DW8OT UT WOS:000383916100030 PM 27586726 ER PT J AU Galovski, TE Peterson, ZD Beagley, MC Strasshofer, DR Held, P Fletcher, TD AF Galovski, Tara E. Peterson, Zoe D. Beagley, Marin C. Strasshofer, David R. Held, Philip Fletcher, Thomas D. TI Exposure to Violence During Ferguson Protests: Mental Health Effects for Law Enforcement and Community Members SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; POLICE OFFICERS; PTSD SYMPTOMS; TRAUMA; SYMPTOMATOLOGY; DEPRESSION; SEVERITY; ANGER AB There is little information available on the mental health effects of exposure to shared community violence such as the August 2014 violence that occurred in Ferguson, Missouri. This study sought to examine the relationship between proximity to community violence and mental health in both community members and police officers. We recruited 565 adults (community, n = 304, and police, n = 261) exposed to the violence in Ferguson to complete measures of proximity to violence, posttraumatic stress, depression, and anger. Using structural equation modeling, we assessed aspects of proximity to violenceconnectedness, direct exposure, fear from exposure, media exposure, reactions to media, and life interruptionas correlates of posttraumatic stress disorder (PTSD) symptoms, depression, and anger. The final model yielded (n = 432), (2)(d = 12) = 7.4, p = .830; comparative fit index = 1.0, root mean square error of approximation = 0 [0, .04]. All aspects of proximity except direct exposure were associated with mental health outcomes. There was no moderation as a function of community versus police. Race moderated the relationship between life interruptions and negative outcomes; interruption was related to distress for White, but not Black community members. Based on group comparisons, community members reported more symptoms of PTSD and depression than law enforcement ((2)(p) = .06 and .02, respectively). Black community members reported more PTSD and depression than White community members ((2)(p) = .05 and .02, respectively). Overall, distress was high, and mental health interventions are likely indicated for some individuals exposed to the Ferguson events. Resumen EFECTOS DE LA EXPOSICIN A LA VIOLENCIA EN FERGUSON Hay muy poca informacion disponible sobre los efectos en la salud mental de la exposicion a violencia comunitaria compartida tales como la violencia en Agosto del 2014 ocurrida en Ferguson, Missouri. Este estudio busco examinar la relacion entre la proximidad a la violencia comunitaria y la salud mental en los miembros de la comunidad y oficiales de policia. Reclutamos 565 adultos (comunidad [n = 304] y policia [n = 261]) expuestos a la violencia en Ferguson para completar medidas de proximidad a la violencia, estres postraumatico, depresion y rabia. Usando la ecuacion de modelamiento estructural, evaluamos los aspectos de proximidad a la violencia - conectividad, exposicion directa, miedo por exposicion, exposicion a los medios, reacciones a los medios e interrupcion de la vida - como correlatos de trastorno por estres postraumatico (TEPT), depresion y rabia. En el modelo final (n = 432),X (2) (d = 12); p = .830, CFI = 1.0, RMSEA = 0 [0,.04], todos los aspectos de la proximidad excepto la exposicion directa se asociaron con los resultados en la salud mental. No hubo moderacion en funcion de la membresia en la comunidad versus la muestra de la policia. La raza modero la relacion entre las interrupciones de vida y los resultados negativos, la interrupcion estuvo relacionada a la angustia para miembros de la comunidad Blancos pero no para los Negros. Basado en comparaciones por grupo, los miembros de la comunidad reportaron mas sintomas de TEPT y depresion que la policia (p(2) = .06 y .02, respectivamente), y los miembros de la comunidad Negra reportaron mas TEPT y depresion que los miembros de la comunidad Blanca (p2 = .05 y .02, respectivamente). En general, la angustia fue alta y las intervenciones de salud mental fueron probablemente indicadas para algunos individuos expuestos a los eventos de Ferguson. C1 [Galovski, Tara E.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Peterson, Zoe D.; Beagley, Marin C.; Strasshofer, David R.] Univ Missouri, Ctr Trauma Recovery, Dept Psychol Sci, St Louis, MO 63121 USA. [Held, Philip] Rush Univ, Med Ctr, Dept, Chicago, IL 60612 USA. RP Galovski, TE (reprint author), VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, 150 South Huntington Ave 116B-3, Boston, MA 02130 USA. EM Tara.Galovski@va.gov OI Peterson, Zoe/0000-0003-2975-1062 FU University of Missouri-St. Louis (UMSL), College of Arts and Sciences (CAS) internal research grant mechanism; College of Nursing, University of Missouri-St. Louis FX Participants' payments were funded by the University of Missouri-St. Louis (UMSL), College of Arts and Sciences (CAS) internal research grant mechanism. Participant recruitment was funded, in part, by the College of Nursing, University of Missouri-St. Louis. NR 33 TC 1 Z9 1 U1 15 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD AUG PY 2016 VL 29 IS 4 BP 283 EP 292 DI 10.1002/jts.22105 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DW2MW UT WOS:000383477500001 PM 27254474 ER PT J AU Shipherd, JC Salters-Pedneault, K Matza, A AF Shipherd, Jillian C. Salters-Pedneault, Kristalyn Matza, Alexis TI Intrusive Cognitive Content and Postdeployment Distress SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; MEMORIES; TRAUMA; SAMPLE; IRAQ; HYPOTHESIS; VALIDATION; DEPLOYMENT; VETERANS; THOUGHTS AB Although intrusive cognitions (ICs) are common posttrauma, little is known about trauma-related IC content, or associations between IC content and posttraumatic adjustment. A mixed-method cross-sectional approach was used in a secondary analysis of IC content and postdeployment distress. Participants were 1,521 U.S. Army soldiers 3-12 months postdeployment reporting their most distressing postdeployment ICs (mean number of ICs reported was 1.20). ICs were transcribed and content was categorized by 13 emergent themes. The most commonly reported ICs were of injury or death (48.2%) and combat (43.5%), and soldiers with probable posttraumatic stress disorder (PTSD; n = 187) were more likely to report the presence of these ICs, (2)s(1) = 35.27, ps < .001, s < .16 than those without probable PTSD (n = 1,331). Other domains also emerged frequently, including ICs about friends (31.0%), family (15.8%), and leadership concerns (13.8%). IC content was a small, but significant correlate of distress after adjusting for combat exposure (R-2 .02, ps .001). The presence of ICs of injury or death, combat, military sexual trauma, health, leadership, and family (s > .06, ps < .02) were unique correlates of distress. Results suggested that ICs about a wide range of topics should be addressed in postdeployment interventions. Resumen Cognicion Intrusiva Post Despliegue Aunque las cogniciones intrusivas (CI) son comunes post trauma, se sabe poco acerca de su contenido relacionado al trauma, o de las asociaciones entre su contenido y la adaptacion post-traumatica. Se uso una aproximacion transversal de metodo mixto en un analisis secundario de contenido de CI y sufrimiento post despliegue. Los participantes fueron 1.521 soldados del ejercito de USA, que reportaron sus mas angustiantes CI post despliegue, 3 a 12 meses posterior a este (el numero promedio de CI reportadas fue 1.20). Las CI fueron transcritas y su contenido fue categorizado en 13 temas emergentes. Las CI mas comunmente reportadas fueron de dano o muerte (48,2%) y combate (43,5%), y los soldados con probable TEPT (n = 187) reportaban con mayor probabilidad la presencia de estas CI, (2)s (1) = 35.27, ps < .001, s < .16 que aquellos sin probable TEPT (n = 1331). Otros dominios, que tambien emergieron frecuentemente, incluyen CI acerca de amigos (31,0%), familia (15,8%) y preocupaciones de liderazgo (13,8%). El contenido de las CI se correlaciono de forma pequena pero significativa con el sufrimiento luego de ajustar por exposicion a combate (R 2 > .02, ps < .001). La presencia de CIs de lesion o muerte, combate, trauma sexual militar salud, liderazgo y familia (s > .06, ps < .02) fueron correlatos unicos de sufrimiento. Los resultados sugieren que se deberia abordar las CI acerca de un amplio rango de temas en las intervenciones post despliegue. C1 [Shipherd, Jillian C.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02118 USA. [Shipherd, Jillian C.; Matza, Alexis] Vet Hlth Adm, Off Patient Care Serv, Lesbian Gay Bisexual & Transgender Program 10P4Y, Washington, DC USA. [Salters-Pedneault, Kristalyn] Eastern Connecticut State Univ, Dept Psychol, Willimantic, CT 06226 USA. [Matza, Alexis] Boston VA Res Inst, Boston, MA USA. RP Shipherd, JC (reprint author), VA Boston Healthcare Syst, Womens Hlth Sci Div 116B 3, Natl Ctr PTSD, 150 South Huntington Ave, Boston, MA 02130 USA. EM Jillian.Shipherd@va.gov FU U.S. Army Medical Research and Materiel Command [W81XWH-09-1-0535] FX This research was supported by the U.S. Army Medical Research and Materiel Command (award# W81XWH-09-1-0535). This trial is registered in the Defense Technical Information Database (DTIC), Accession #579178. NR 37 TC 0 Z9 0 U1 12 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD AUG PY 2016 VL 29 IS 4 BP 301 EP 308 DI 10.1002/jts.22113 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DW2MW UT WOS:000383477500003 PM 27405098 ER PT J AU Jackson, CE Green, JD Bovin, MJ Vasterling, JJ Holowka, DW Ranganathan, G Rosen, RC Keane, TM Marx, BP AF Jackson, Colleen E. Green, Jonathan D. Bovin, Michelle J. Vasterling, Jennifer J. Holowka, Darren W. Ranganathan, Gayatri Rosen, Raymond C. Keane, Terence M. Marx, Brian P. TI Mild Traumatic Brain Injury, PTSD, and Psychosocial Functioning Among Male and Female US OEF/OIF Veterans SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; ENDURING FREEDOM; NATIONAL-GUARD; IRAQ; HEALTH; AFGHANISTAN; SOLDIERS; METAANALYSIS; ASSOCIATION; IMPAIRMENT AB This study examined the unique and combined relationship between mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) with psychosocial functioning in a cohort of 1,312 U.S. male and female veterans of Operations Enduring Freedom (OEF) and Iraqi Freedom (OIF) enrolled in the Veterans After-Discharge Longitudinal Registry (Project VALOR). We assessed mTBI with structured screening questions reflective of current TBI classification standards and PTSD via the SCID-IV PTSD module; all other variables were assessed by self-report questionnaires. We identified significant diagnostic group differences in psychosocial functioning for both sexes. Individuals with PTSD, with or without a history of mTBI, reported significantly worse psychosocial functioning than individuals with mTBI alone or neither mTBI nor PTSD (males, (2)(p) = .11, p < .001; females, (2)(p) = .14, p < .001), even after adjusting for demographics and severity of chronic pain. The results suggested that veterans experiencing PTSD, regardless of whether they had a history of mTBI, were at increased risk for long-term psychosocial impairment. Further research examining possible benefits from improved access to resources and treatment to address these needs would be valuable. Resumen Este estudio examino la relacion unica y combinada entre la lesion cerebral traumatica leve (LCTL) y trastorno por estres postraumatico (TEPT) con el funcionamiento psicosocial en una cohorte de 1.312 hombres y mujeres veteranos de las operaciones Enduring Freedom (OEF) y Libertad Iraqui (OIF) inscritos en el Registro Longitudinal de Veteranos despues de descargos (Proyecto VALOR). Se evaluo LCTL con preguntas de screening estructuradas que reflejan los criterios de clasificacion de LCT actual y trastorno por estres postraumatico a traves del modulo de TEPT SCID-IV; todas las demas variables se evaluaron mediante cuestionarios de auto-reporte. Se identificaron diferencias significativas entre los grupos de diagnostico en el funcionamiento psicosocial para ambos sexos, de tal manera que las personas con trastorno de estres postraumatico, con o sin historial de LCTL, reportaron significativamente peor funcionamiento psicosocial en comparacion con los individuos con LCTL solo o los que no tenian LCTL ni trastorno por estres postraumatico (hombres, 2 p = 0,11, p <0,001; mujeres, 2 p = 0,14, p <0,001), incluso despues de ajustar las variables demograficas y la severidad del dolor cronico. Los resultados sugieren que los veteranos que experimentan trastorno por estres postraumatico, independientemente de si tenian un historial de LCTL, estaban en mayor riesgo de deterioro psicosocial a largo plazo. Futuras investigaciones que examinen los posibles beneficios de un acceso mejorado a los recursos y el tratamiento para dirigir estas necesidades serian valiosas. C1 [Jackson, Colleen E.] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr GRECC, Boston, MA USA. [Jackson, Colleen E.] VA Boston Healthcare Syst, Translat Res Ctr TBI & Stress Disorders TRACTS, Boston, MA USA. [Jackson, Colleen E.; Green, Jonathan D.; Bovin, Michelle J.; Vasterling, Jennifer J.; Holowka, Darren W.; Keane, Terence M.; Marx, Brian P.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Green, Jonathan D.] VA Boston Healthcare Syst, Res Serv, Boston, MA USA. [Bovin, Michelle J.; Vasterling, Jennifer J.; Holowka, Darren W.; Keane, Terence M.; Marx, Brian P.] VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, Boston, MA USA. [Ranganathan, Gayatri; Rosen, Raymond C.] New England Res Inst, 9 Galen St, Watertown, MA 02172 USA. RP Marx, BP (reprint author), VA Boston Healthcare Syst 116B 4, Natl Ctr PTSD, Behav Sci Div, 150 South Huntington Ave, Boston, MA 02130 USA. EM brian.marx@va.gov NR 39 TC 0 Z9 0 U1 10 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD AUG PY 2016 VL 29 IS 4 BP 309 EP 316 DI 10.1002/jts.22110 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DW2MW UT WOS:000383477500004 PM 27405050 ER PT J AU DiMauro, J Renshaw, KD Smith, BN Vogt, D AF DiMauro, Jennifer Renshaw, Keith D. Smith, Brian N. Vogt, Dawne TI Perceived Support From Multiple Sources: Associations With PTSD Symptoms SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; SOCIAL SUPPORT; GENDER-DIFFERENCES; MULTIDIMENSIONAL SCALE; OEF/OIF VETERANS; MENTAL-HEALTH; RISK-FACTORS; DEPLOYMENT; COMBAT; METAANALYSIS AB Perceived social support is negatively associated with severity of posttraumatic stress disorder (PTSD), but the literature lacks data about specific sources of support. Using 2 service member (SM) samples (n = 207 and 465), this study examined perceived support from family/friends and the broader public. SMs perceived high support from both sources. In multivariate regressions, perceived support from the broader public was not significantly associated with severity of PTSD symptoms, but it demonstrated a nearly identical effect size ( = -.21) as support from family/friends ( = -.23) in a sample of active duty and National Guard/Reserve SMs. We found that, SMs perceived high levels of support from the broader public, with modest evidence that such perceptions may relate to severity of PTSD. Resumen Apoyo Percibido desde Multiples Fuentes en TEPT El apoyo social percibido esta negativamente asociado con la severidad del trastorno por estres postraumatico (TEPT) pero la literatura carece de datos acerca de las fuentes de apoyo. Utilizando 2 muestras de miembros de servicio (MS) (n = 207; 465), este estudio examino el apoyo percibido desde la familia/amigos y del publico en general. Los MSs percibieron alto apoyo de ambas fuentes. En una regresion multivariada, el apoyo percibido desde el publico en general no estuvo significativamente asociado con la severidad de los sintomas de TEPT, pero demostro un casi identico tamano del efecto ( = -.21) como el apoyo desde la familia/amigos ( = -.23) en una muestra de servicio activo y Guardia Nacional/ Reserva MSs. En conclusion, MSs percibieron altos niveles de apoyo desde el publico en general, con una modesta evidencia que tales percepciones pueden estar relacionadas con la severidad de TEPT. C1 [DiMauro, Jennifer; Renshaw, Keith D.] George Mason Univ, Dept Psychol, 4400 Univ Dr,MSN 3F5, Fairfax, VA 22030 USA. [Smith, Brian N.; Vogt, Dawne] VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Smith, Brian N.; Vogt, Dawne] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP DiMauro, J (reprint author), George Mason Univ, Dept Psychol, 4400 Univ Dr,MSN 3F5, Fairfax, VA 22030 USA. EM jdimauro@gmu.edu FU Department of Veterans Affairs, Health Services Research and Development Service [DHI 05-130-3, DHI 09-086] FX This project was supported by two Department of Veterans Affairs, Health Services Research and Development Service grants: "Further Development and Validation of the DRRI" (DHI 05-130-3), Dawne Vogt, Principal Investigator; and "Validation of Modified DRRI Scales in a National Sample of OEF/OIF Veterans" (DHI 09-086), Dawne Vogt, Principal Investigator. NR 35 TC 0 Z9 0 U1 10 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD AUG PY 2016 VL 29 IS 4 BP 332 EP 339 DI 10.1002/jts.22114 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DW2MW UT WOS:000383477500007 PM 27459310 ER PT J AU Sawyer, AT Liverant, GI Jun, JJ Lee, DJ Cohen, AL Dutra, SJ Pizzagalli, DA Sloan, DM AF Sawyer, Alice T. Liverant, Gabrielle I. Jun, Janie J. Lee, Daniel J. Cohen, Andrew L. Dutra, Sunny J. Pizzagalli, Diego A. Sloan, Denise M. TI Punishment Learning in US Veterans With Posttraumatic Stress Disorder SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID DEPRESSION; SCALE AB Learning processes have been implicated in the development and course of posttraumatic stress disorder (PTSD); however, little is currently known about punishment-based learning in PTSD. The current study investigated impairments in punishment-based learning in U.S. veterans. We expected that veterans with PTSD would demonstrate greater punishment-based learning compared to a non-PTSD control group. We compared a PTSD group with and without co-occurring depression (n = 27) to a control group (with and without trauma exposure) without PTSD or depression (n = 29). Participants completed a computerized probabilistic punishment-based learning task. Compared to the non-PTSD control group, veterans with PTSD showed significantly greater punishment-based learning. Specifically, there was a significant Block x Group interaction, F(1, 54) = 4.12, p = .047, (2) = .07. Veterans with PTSD demonstrated greater change in response bias for responding toward a less frequently punished stimulus across blocks. The observed hypersensitivity to punishment in individuals with PTSD may contribute to avoidant responses that are not specific to trauma cues. Resumen Aprendizaje por castigo y TEPT El procesamiento del aprendizaje ha estado implicado en el desarrollo y curso del trastorno por estres postraumatico (TEPT); sin embargo, poco se sabe actualmente acerca del aprendizaje basado en el castigo en el TEPT. El presente estudio investigo los deterioros potenciales en el aprendizaje basado en el castigo entre participantes veteranos. Nosotros esperabamos que los veteranos con TEPT pudieran demostrar mayor aprendizaje basado en el castigo comparados con el grupo control sin TEPT. Comparamos un grupo con TEPT con y sin depresion comorbida (n = 27) a un grupo control (con y sin exposicion a trauma) sin TEPT o depresion (n = 29). Los veteranos completaron una tarea de aprendizaje basado en el castigo probabilistico computarizado. En relacion con el grupo control sin TEPT, los veteranos con TEPT demostraron significativamente mayor aprendizaje basado en el castigo. En concreto, habia un Bloque significativo x interaccion del grupo, F(1,54) = 4.12, p = .047, ?(2) = .07, tales que los veteranos con TEPT demostraron mayores cambios en el sesgo de respuesta para responder a un estimulo que es castigado con menos frecuencia a traves de bloques. En consecuencia, la hipersensibilidad al castigo en los individuos con TEPT puede contribuir a las respuestas de evitacion que no son especificos a las senales de trauma. Se discuten las implicaciones clinicas junto con la consideracion de la comorbilidad con depresion. C1 [Sawyer, Alice T.; Jun, Janie J.; Lee, Daniel J.; Sloan, Denise M.] VA Boston Healthcare Syst, 150 S Huntington Ave 116B-4, Boston, MA 02130 USA. [Liverant, Gabrielle I.] Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. [Jun, Janie J.; Lee, Daniel J.; Sloan, Denise M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Lee, Daniel J.] Auburn Univ, Dept Psychol, Auburn, AL 36849 USA. [Cohen, Andrew L.; Pizzagalli, Diego A.] McLean Hosp, 115 Mill St, Belmont, MA 02178 USA. [Cohen, Andrew L.; Pizzagalli, Diego A.] Harvard Med Sch, Belmont, MA USA. [Dutra, Sunny J.] Yale Univ, Dept Psychol, New Haven, CT USA. [Sloan, Denise M.] VA Natl Ctr PTSD, Behav Sci Div, Boston, MA USA. RP Sloan, DM (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave 116B-4, Boston, MA 02130 USA. EM denise.sloan@va.gov FU VA National Center for PTSD, Behavioral Science Division; NIMH [R01 MH068376, R01 MH101521] FX This work was supported by VA National Center for PTSD, Behavioral Science Division. Diego A. Pizzagalli was partially supported by NIMH grants R01 MH068376 and R01 MH101521. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH and the Department of Veteran Affairs. NR 23 TC 0 Z9 0 U1 4 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD AUG PY 2016 VL 29 IS 4 BP 374 EP 378 DI 10.1002/jts.22109 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DW2MW UT WOS:000383477500012 PM 27459209 ER PT J AU Sautter, FJ Glynn, SM Becker-Cretu, JJ Senturk, D Armelie, AP Wielt, DB AF Sautter, Frederic J. Glynn, Shirley M. Becker-Cretu, Julia J. Senturk, Damla Armelie, Aaron P. Wielt, Dustin B. TI Structured Approach Therapy for Combat-Related PTSD in Returning US Veterans: Complementary Mediation by Changes in Emotion Functioning SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; IRAQ; AFGHANISTAN; SYMPTOMS; TRIAL; SCALE; FEAR; WAR AB To address the impact of combat-related posttraumatic stress disorder (PTSD) on U.S. Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) veterans, the investigators developed a 12-session manualized PTSD treatment for couples called structured approach therapy (SAT). A randomized controlled trial had shown that 29 OEF/OIF veterans with combat-related PTSD who had participated in SAT showed significantly greater reductions in PTSD compared to 28 veterans receiving a 12-session PTSD family education intervention (Sautter, Glynn, Cretu, Senturk, & Vaught, 2015). We conducted supplemental follow-up and mediation analyses, which tested the hypothesis that changes in emotion functioning play a significant role in the decreases in PTSD symptoms primarily observed in veterans who had received SAT. Veterans assigned to the SAT condition showed significantly greater decreases than those assigned to PTSD family education in emotion regulation problems (p < .001, Cohen's f(2) = .18) and fear of intense emotions (p <.001, Cohen's f2 =.152). Decreases in both emotion regulation problems (mediated effect: ab =.36), and fear of intense emotions (mediated effect: ab =.24) were found to be complementary mediators of reductions in PTSD symptoms greater with SAT. These findings suggest that SAT may aid veterans in improving their ability to regulate trauma-related emotions. C1 [Sautter, Frederic J.] Southeast Louisiana Vet Hlth Care Syst, New Orleans, LA USA. [Sautter, Frederic J.; Becker-Cretu, Julia J.; Armelie, Aaron P.] Tulane Univ, Sch Med, Dept Psychiat, 1430 Tulane Ave, New Orleans, LA 70112 USA. [Glynn, Shirley M.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Glynn, Shirley M.] Univ Calif Los Angeles, Welcome Back Vet Family Resilience Ctr, Los Angeles, CA USA. [Senturk, Damla] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA USA. [Senturk, Damla] Univ Calif Los Angeles, Dept Stat, Los Angeles, CA USA. [Wielt, Dustin B.] Raymond G Murphy VA Med Ctr, Albuquerque, NM USA. RP Sautter, FJ (reprint author), Tulane Univ, Sch Med, Dept Psychiat & Behav Sci, 1440 Canal St TB 53, New Orleans, LA 70112 USA. EM fredericsautter@msn.com FU VA Research Rehabilitation and Development (RRD) Program [B6756R]; South Central Mental Illness Research Education and Clinical Center (MIRECC) FX This work was supported in part by a Merit Review grant (No. B6756R) from the VA Research Rehabilitation and Development (RR&D) Program and a Supplemental Funding Award from the South Central Mental Illness Research Education and Clinical Center (MIRECC) to Frederic J. Sautter. The authors thank Dr. Michelle Sherman for her consultation in developing both treatment manuals, and Dr. Amanda Vaught, Marin Casselli, and Allison Abel for their contributions. NR 15 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD AUG PY 2016 VL 29 IS 4 BP 384 EP 387 DI 10.1002/jts.22120 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DW2MW UT WOS:000383477500014 PM 27472747 ER PT J AU Campo, M Al-Halabi, H Khandekar, M Shaw, AT Sequist, LV Willers, H AF Campo, Meghan Al-Halabi, Hani Khandekar, Melin Shaw, Alice T. Sequist, Lecia V. Willers, Henning TI Integration of Stereotactic Body Radiation Therapy With Tyrosine Kinase Inhibitors in Stage IV Oncogene-Driven Lung Cancer SO ONCOLOGIST LA English DT Article ID GROWTH-FACTOR-RECEPTOR; PHASE I/II TRIAL; DOSE-ESCALATION TRIAL; ACQUIRED-RESISTANCE; BRAIN METASTASES; OLIGOMETASTATIC LESIONS; EGFR MUTATIONS; II-TRIAL; EXTRACRANIAL OLIGOMETASTASES; OLIGOPROGRESSIVE DISEASE AB Genotype-based selection of patients for targeted therapies has had a substantial impact on the treatment of non-small cell lung cancers (NSCLCs). Tyrosine kinase inhibitors (TKIs) directed at cancers driven by oncogenes, such as epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangements, often achieve dramatic responses and result in prolonged survival compared with chemotherapy. However, TKI resistance invariably develops. Disease progression can be limited to only one or a few sites and might not be symptomatic, raising the important question of whether this type of oligoprogression warrants a change in systemic therapy or consideration of local treatment. Recent clinical observations suggest a growing role for stereotactic body radiation therapy (SBRT) in the treatment of oligoprogressive and perhaps even oligopersistent disease (primary and/or metastases) in oncogene-driven NSCLC. SBRTmight allow patients to continue with existing TKI treatments longer and delay the need to switch to other systemic options. We review the current data with regard to the use of SBRT for metastatic NSCLC and particularly oncogene-driven disease. Although there is great promise in the marriage of targeted therapies with SBRT, prospective data are urgently needed. In the meantime, such strategies are being used in carefully selected patients, with risk-adapted SBRT dose-fractionation regimens used to optimize the therapeutic index. C1 [Campo, Meghan] Dana Farber Partners CancerCare, Hematol Oncol Fellowship Program, Boston, MA USA. [Al-Halabi, Hani; Khandekar, Melin; Willers, Henning] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Shaw, Alice T.; Sequist, Lecia V.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Shaw, Alice T.; Sequist, Lecia V.] Harvard Med Sch, Boston, MA USA. RP Willers, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. EM hwillers@mgh.harvard.edu NR 107 TC 1 Z9 1 U1 3 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD AUG PY 2016 VL 21 IS 8 BP 964 EP 973 DI 10.1634/theoncologist.2015-0508 PG 10 WC Oncology SC Oncology GA DW1HC UT WOS:000383392900009 PM 27354669 ER PT J AU Fathi, AT Chi, AS AF Fathi, Amir T. Chi, Andrew S. TI Urine 2-Hydroxyglutarate in Glioma Reply SO ONCOLOGIST LA English DT Letter C1 [Fathi, Amir T.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02115 USA. [Chi, Andrew S.] NYU, Langone Med Ctr, Laura & Isaac Perlmutter Canc Ctr, New York, NY USA. RP Fathi, AT (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02115 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD AUG PY 2016 VL 21 IS 8 DI 10.1634/theoncologist.2016-0138 PG 1 WC Oncology SC Oncology GA DW1HC UT WOS:000383392900018 ER PT J AU Baeten, JM Heffron, R Kidoguchi, L Mugo, NR Katabira, E Bukusi, EA Asiimwe, S Haberer, JE Morton, J Ngure, K Bulya, N Odoyo, J Tindimwebwa, E Hendrix, C Marzinke, MA Ware, NC Wyatt, MA Morrison, S Haugen, H Mujugira, A Donnell, D Celum, C AF Baeten, Jared M. Heffron, Renee Kidoguchi, Lara Mugo, Nelly R. Katabira, Elly Bukusi, Elizabeth A. Asiimwe, Stephen Haberer, Jessica E. Morton, Jennifer Ngure, Kenneth Bulya, Nulu Odoyo, Josephine Tindimwebwa, Edna Hendrix, Craig Marzinke, Mark A. Ware, Norma C. Wyatt, Monique A. Morrison, Susan Haugen, Harald Mujugira, Andrew Donnell, Deborah Celum, Connie CA Partners Demonstration Project Tea TI Integrated Delivery of Antiretroviral Treatment and Pre-exposure Prophylaxis to HIV-1-Serodiscordant Couples: A Prospective Implementation Study in Kenya and Uganda SO PLOS MEDICINE LA English DT Article ID AFRICAN WOMEN; HIV-INFECTION; COST-EFFECTIVENESS; PREVENTION; THERAPY; MEN AB Background Antiretroviral-based interventions for HIV-1 prevention, including antiretroviral therapy (ART) to reduce the infectiousness of HIV-1 infected persons and pre-exposure prophylaxis (PrEP) to reduce the susceptibility of HIV-1 uninfected persons, showed high efficacy for HIV-1 protection in randomized clinical trials. We conducted a prospective implementation study to understand the feasibility and effectiveness of these interventions in delivery settings. Methods and Findings Between November 5, 2012, and January 5, 2015, we enrolled and followed 1,013 heterosexual HIV-1-serodiscordant couples in Kenya and Uganda in a prospective implementation study. ART and PrEP were offered through a pragmatic strategy, with ART promoted for all couples and PrEP offered until 6 mo after ART initiation by the HIV-1 infected partner, permitting time to achieve virologic suppression. One thousand thirteen couples were enrolled, 78% of partnerships initiated ART, and 97% used PrEP, during a median follow-up of 0.9 years. Objective measures of adherence to both prevention strategies demonstrated high use (>= 85%). Given the low HIV-1 incidence observed in the study, an additional analysis was added to compare observed incidence to incidence estimated under a simulated counterfactual model constructed using data from a prior prospective study of HIV-1-serodiscordant couples. Counterfactual simulations predicted 39.7 HIV-1 infections would be expected in the population at an incidence of 5.2 per 100 person-years (95% CI 3.7-6.9). However, only two incident HIV-1 infections were observed, at an incidence of 0.2 per 100 person-years (95% CI 0.0-0.9, p < 0.0001 versus predicted). The use of a non-concurrent comparison of HIV-1 incidence is a potential limitation of this approach; however, it would not have been ethical to enroll a contemporaneous population not provided access to ART and PrEP. Conclusions Integrated delivery of time-limited PrEP until sustained ART use in African HIV-1-serodiscordant couples was feasible, demonstrated high uptake and adherence, and resulted in near elimination of HIV-1 transmission, with an observed HIV incidence of < 0.5% per year compared to an expected incidence of > 5% per year. C1 [Baeten, Jared M.; Heffron, Renee; Kidoguchi, Lara; Mugo, Nelly R.; Bukusi, Elizabeth A.; Morton, Jennifer; Morrison, Susan; Haugen, Harald; Mujugira, Andrew; Donnell, Deborah; Celum, Connie] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA. [Baeten, Jared M.; Celum, Connie] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Baeten, Jared M.; Heffron, Renee; Celum, Connie] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Mugo, Nelly R.] Kenya Govt Med Res Ctr, Clin Res Ctr, Nairobi, Kenya. [Katabira, Elly; Bulya, Nulu] Makerere Univ, Infect Dis Inst, Kampala, Uganda. [Bukusi, Elizabeth A.; Odoyo, Josephine] Kenya Govt Med Res Ctr, Ctr Microbiol Res, Nairobi, Kenya. [Asiimwe, Stephen; Tindimwebwa, Edna] Kabwohe Clin Res Ctr, Kabwohe, Uganda. [Haberer, Jessica E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ngure, Kenneth] Jomo Kenyatta Univ Agr & Technol, Coll Hlth Sci, Nairobi, Kenya. [Marzinke, Mark A.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Ware, Norma C.; Wyatt, Monique A.] Harvard Med Sch, Dept Global Hlth & Social Med, Boston, MA USA. [Wyatt, Monique A.] Harvard Global, Cambridge, MA USA. [Donnell, Deborah] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1124 Columbia St, Seattle, WA 98104 USA. RP Baeten, JM (reprint author), Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.; Baeten, JM (reprint author), Univ Washington, Dept Med, Seattle, WA 98195 USA.; Baeten, JM (reprint author), Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. EM jbaeten@uw.edu RI Hendrix, Craig/G-4182-2014 OI Hendrix, Craig/0000-0002-5696-8665 FU National Institute of Mental Health of the US National Institutes of Health [R01 MH095507]; Bill & Melinda Gates Foundation [OPP1056051]; US Agency for International Development [AID-OAA-A-12-00023] FX The Partners Demonstration Project was funded by the National Institute of Mental Health of the US National Institutes of Health (grant R01 MH095507), the Bill & Melinda Gates Foundation (grant OPP1056051), and through the US Agency for International Development (cooperative agreement AID-OAA-A-12-00023). Gilead Sciences donated the PrEP medication but had no role in data collection or analysis. The results and interpretation presented here do not necessarily reflect the views of the study funders. The study funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. NR 22 TC 5 Z9 5 U1 1 U2 1 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 AUG PY 2016 VL 13 IS 8 AR e1002099 DI 10.1371/journal.pmed.1002099 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA DW0UD UT WOS:000383357400017 PM 27552090 ER PT J AU Ly, J Sathananthan, V Griffiths, T Kanjee, Z Kenny, A Gordon, N Basu, G Battistoli, D Dorr, L Lorenzen, B Thomson, DR Waters, A Moore, UG Roberts, R Smith, WL Siedner, MJ Kraemer, JD AF Ly, John Sathananthan, Vidiya Griffiths, Thomas Kanjee, Zahir Kenny, Avi Gordon, Nicholas Basu, Gaurab Battistoli, Dale Dorr, Lorenzo Lorenzen, Breeanna Thomson, Dana R. Waters, Ami Moore, Uriah G. Roberts, Ruth Smith, Wilmot L. Siedner, Mark J. Kraemer, John D. TI Facility-Based Delivery during the Ebola Virus Disease Epidemic in Rural Liberia: Analysis from a Cross-Sectional, Population-Based Household Survey SO PLOS MEDICINE LA English DT Article ID SUB-SAHARAN AFRICA; NOVEMBER 2014; WEST-AFRICA; HEALTH; MORTALITY; OUTBREAK; DISTRICT; LESSONS; NEWBORN; SYSTEM AB Background The Ebola virus disease (EVD) epidemic has threatened access to basic health services through facility closures, resource diversion, and decreased demand due to community fear and distrust. While modeling studies have attempted to estimate the impact of these disruptions, no studies have yet utilized population-based survey data. Methods and Findings We conducted a two-stage, cluster-sample household survey in Rivercess County, Liberia, in March-April 2015, which included a maternal and reproductive health module. We constructed a retrospective cohort of births beginning 4 y before the first day of survey administration (beginning March 24, 2011). We then fit logistic regression models to estimate associations between our primary outcome, facility-based delivery (FBD), and time period, defined as the pre-EVD period (March 24, 2011-June 14, 2014) or EVD period (June 15, 2014-April 13, 2015). We fit both univariable and multivariable models, adjusted for known predictors of facility delivery, accounting for clustering using linearized standard errors. To strengthen causal inference, we also conducted stratified analyses to assess changes in FBD by whether respondents believed that health facility attendance was an EVD risk factor. A total of 1,298 women from 941 households completed the survey. Median age at the time of survey was 29 y, and over 80% had a primary education or less. There were 686 births reported in the pre-EVD period and 212 in the EVD period. The unadjusted odds ratio of facility-based delivery in the EVD period was 0.66 (95% confidence interval [CI] 0.48-0.90, p-value = 0.010). Adjustment for potential confounders did not change the observed association, either in the principal model (adjusted odds ratio [AOR] = 0.70, 95% CI 0.50-0.98, p = 0.037) or a fully adjusted model (AOR = 0.69, 95% CI 0.50-0.97, p = 0.033). The association was robust in sensitivity analyses. The reduction in FBD during the EVD period was observed among those reporting a belief that health facilities are or may be a source of Ebola transmission (AOR = 0.59, 95% CI 0.36-0.97, p = 0.038), but not those without such a belief (AOR = 0.90, 95% CI 0.59-1.37, p = 0.612). Limitations include the possibility of FBD secular trends coincident with the EVD period, recall errors, and social desirability bias. Conclusions We detected a 30% decreased odds of FBD after the start of EVD in a rural Liberian county with relatively few cases. Because health facilities never closed in Rivercess County, this estimate may under-approximate the effect seen in the most heavily affected areas. These are the first population-based survey data to show collateral disruptions to facility-based delivery caused by the West African EVD epidemic, and they reinforce the need to consider the full spectrum of implications caused by public health emergencies. C1 [Ly, John; Waters, Ami] Last Mile Hlth, Med Team, Zwedru, Liberia. [Sathananthan, Vidiya; Griffiths, Thomas; Kenny, Avi; Gordon, Nicholas; Basu, Gaurab] Last Mile Hlth, Monitoring & Evaluat Team, Zwedru, Liberia. [Kanjee, Zahir] Brigham & Womens Hosp, Div Global Hlth Equ, 75 Francis St, Boston, MA 02115 USA. [Basu, Gaurab] Cambridge Hlth Alliance, Cambridge, MA USA. [Basu, Gaurab; Siedner, Mark J.] Harvard Med Sch, Boston, MA 02115 USA. [Battistoli, Dale; Dorr, Lorenzo; Lorenzen, Breeanna] Last Mile Hlth, Implementat Team, Cestos City, Liberia. [Thomson, Dana R.] Harvard Med Sch, Dept Global Hlth & Social Med, Boston, MA USA. [Moore, Uriah G.; Roberts, Ruth; Smith, Wilmot L.] Liberian Minist Hlth & Social Welf, Rivercess Cty Hlth Team, Cestos City, Liberia. [Siedner, Mark J.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Kraemer, John D.] Georgetown Univ, Dept Hlth Syst Adm, Washington, DC 20057 USA. [Kraemer, John D.] Georgetown Univ, African Studies Program, Washington, DC 20057 USA. [Kanjee, Zahir] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Waters, Ami] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. RP Siedner, MJ (reprint author), Harvard Med Sch, Boston, MA 02115 USA.; Siedner, MJ (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA.; Kraemer, JD (reprint author), Georgetown Univ, Dept Hlth Syst Adm, Washington, DC 20057 USA.; Kraemer, JD (reprint author), Georgetown Univ, African Studies Program, Washington, DC 20057 USA. EM msiedner@mgh.harvard.edu; jdk32@georgetown.edu OI Kenny, Avi/0000-0002-9465-7307 FU Direct Relief; National Institutes of Health [K23 MH099916]; UBS Optimus Foundation FX Direct Relief and UBS Optimus Foundation provided programmatic evaluation funds to Last Mile Health for the survey on which this analysis was conducted (no grant identification numbers). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. MJS receives research support from the National Institutes of Health (K23 MH099916). NR 84 TC 3 Z9 3 U1 3 U2 3 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 AUG PY 2016 VL 13 IS 8 AR e1002096 DI 10.1371/journal.pmed.1002096 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA DW0UD UT WOS:000383357400016 PM 27482706 ER PT J AU Popp, I Grosu, AL Niedermann, G Duda, DG AF Popp, Ilinca Grosu, Anca Ligia Niedermann, Gabriele Duda, Dan G. TI Immune modulation by hypofractionated stereotactic radiation therapy: Therapeutic implications SO RADIOTHERAPY AND ONCOLOGY LA English DT Review DE SBRT; SRS; Checkpoint blockade; Abscopal effect ID CELL LUNG-CANCER; COLONY-STIMULATING FACTOR; MONOCLONAL-ANTIBODY THERAPY; RESISTANT PROSTATE-CANCER; PHASE I/II TRIAL; CD8(+) T-CELLS; BREAST-CANCER; TUMOR-CELLS; HEPATOCELLULAR-CARCINOMA; ANTITUMOR IMMUNITY AB Stereotactic body radiation therapy (SBRT) has become an attractive treatment modality and a safe, non-invasive alternative to surgery to control primary or secondary malignant tumors. While emphasis has been on the local tumor control as a treatment objective for SBRT, the rare but intriguing observations of abscopal (or out-of-field) effects have pointed to the exciting possibility of activating anti-tumor immunity by using high-dose radiation. This review summarizes the available evidence supporting immune modulation by SBRT alone, as well as its potential combination with immunotherapy. Promising preclinical research has revealed an array of immune changes following SBRT, which could affect the balance between anti-tumor immunity and tumor-promoting immunosuppression. However, shifting this balance in the clinical setting to obtain survival benefits has rarely been achieved so far, emphasizing the need for a better understanding of the interactions between high-dose radiotherapy and immunity or immunotherapy. Nevertheless, the combination of SBRT with immunotherapy, particularly with immune checkpoint blockers, has the clear potential to substantially increase the rate of abscopal effects. This warrants further research in this area, both in mechanistic preclinical studies and in clinical trials incorporating correlative studies. (C) 2016 Elsevier Ireland Ltd. All rights reserved. C1 [Popp, Ilinca; Grosu, Anca Ligia; Niedermann, Gabriele] Univ Med Ctr Freiburg, Dept Radiat Oncol, Freiburg, Germany. [Popp, Ilinca; Grosu, Anca Ligia; Niedermann, Gabriele] German Canc Consortium DKTK, Partner Site Freiburg, Freiburg, Germany. [Duda, Dan G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Labs, Boston, MA USA. [Duda, Dan G.] Harvard Med Sch, Boston, MA USA. RP Duda, DG (reprint author), Massachusetts Gen Hosp, 100 Blossom St, Boston, MA 02114 USA. EM gduda@partners.org NR 118 TC 3 Z9 3 U1 6 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD AUG PY 2016 VL 120 IS 2 BP 185 EP 194 DI 10.1016/j.radonc.2016.07.013 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DW0EQ UT WOS:000383314100001 PM 27495145 ER PT J AU Huynh, E Coroller, TP Narayan, V Agrawal, V Hou, Y Romano, J Franco, I Mak, RH Aerts, HJWL AF Huynh, Elizabeth Coroller, Thibaud P. Narayan, Vivek Agrawal, Vishesh Hou, Ying Romano, John Franco, Idalid Mak, Raymond H. Aerts, Hugo J. W. L. TI CT-based radiomic analysis of stereotactic body radiation therapy patients with lung cancer SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Radiomics; Imaging; Stereotactic body radiation therapy; Lung cancer ID FALSE DISCOVERY RATE; PROSPECTIVE PHASE-II; EARLY-STAGE; ADJUVANT CHEMOTHERAPY; SURVIVAL MODELS; RADIOTHERAPY; OUTCOMES; SCANS; VARIABILITY; PERFORMANCE AB Background: Radiomics uses a large number of quantitative imaging features that describe the tumor phenotype to develop imaging biomarkers for clinical outcomes. Radiomic analysis of pre-treatment computed-tomography (CT) scans was investigated to identify imaging predictors of clinical outcomes in early stage non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT). Materials and methods: CT images of 113 stage I-II NSCLC patients treated with SBRT were analyzed. Twelve radiomic features were selected based on stability and variance. The association of features with clinical outcomes and their prognostic value (using the concordance index (CI)) was evaluated. Radiomic features were compared with conventional imaging metrics (tumor volume and diameter) and clinical parameters. Results: Overall survival was associated with two conventional features (volume and diameter) and two radiomic features (LoG 3D run low gray level short run emphasis and stats median). One radiomic feature (Wavelet LLH stats range) was significantly prognostic for distant metastasis (CI = 0.67, q-value < 0.1), while none of the conventional and clinical parameters were. Three conventional and four radiomic features were prognostic for overall survival. Conclusion: This exploratory analysis demonstrates that radiomic features have potential to be prognostic for some outcomes that conventional imaging metrics cannot predict in SBRT patients. (C) 2016 Elsevier Ireland Ltd. All rights reserved. C1 [Huynh, Elizabeth; Coroller, Thibaud P.; Narayan, Vivek; Agrawal, Vishesh; Hou, Ying; Romano, John; Franco, Idalid; Mak, Raymond H.; Aerts, Hugo J. W. L.] Harvard Med Sch, Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Aerts, Hugo J. W. L.] Harvard Med Sch, Brigham & Womens Hosp, Dept Radiol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Huynh, E (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. EM ehuynh@lroc.harvard.edu RI Aerts, Hugo/P-6350-2015; OI Aerts, Hugo/0000-0002-2122-2003; Coroller, Thibaud/0000-0001-7662-8724 FU National Institute of Health [NIH-USA U24CA194354, NIH-USA U01CA190234]; Kaye Scholar Award; Brigham and Women's Hospital Department of Radiation Oncology Clinical Translational Grant FX Authors acknowledge financial support from the National Institute of Health (NIH-USA U24CA194354, and NIH-USA U01CA190234). This project was partially funded by the Kaye Scholar Award and the Brigham and Women's Hospital Department of Radiation Oncology Clinical Translational Grant. The study sponsors had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 49 TC 3 Z9 3 U1 9 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD AUG PY 2016 VL 120 IS 2 BP 258 EP 266 DI 10.1016/j.radonc.2016.05.024 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DW0EQ UT WOS:000383314100013 PM 27296412 ER PT J AU Linnoila, J Pittock, SJ AF Linnoila, Jenny Pittock, Sean J. TI Autoantibody-Associated Central Nervous System Neurologic Disorders SO SEMINARS IN NEUROLOGY LA English DT Article DE paraneoplastic; autoimmune; encephalitis; antibodies; immunotherapy ID METHYL-D-ASPARTATE; NMDA RECEPTOR ENCEPHALITIS; PARANEOPLASTIC CEREBELLAR DEGENERATION; HERPES-SIMPLEX ENCEPHALITIS; ANTIBODY-ASSOCIATED ENCEPHALOPATHY; CALCIUM-CHANNEL ANTIBODIES; SLEEP BEHAVIOR DISORDER; BRAIN-STEM ENCEPHALITIS; RAPID-EYE-MOVEMENT; CELL LUNG-CANCER AB Autoimmune neurology is a rapidly evolving new subspecialty driven by the discovery of novel neural- (neuronal- or glial-) specific autoantibodies and their target antigens. The neurologic manifestations affecting the central nervous system include encephalitis, dementia, epilepsy, and movement and sleep disorders. Laboratory testing is now available for most of these neural-specific autoantibodies, which serve as diagnostic markers, in some instances directing the physician toward specific cancer types (e.g., N-methyl-D-aspartic acid receptor antibodies for teratoma, collapsin response mediator protein 5 for small-cell lung cancer) and assisting in therapeutic decision making. Antibodies targeting intracellular proteins serve as markers of cytotoxic effector T-cell mediated injury, which is generally poorly responsive to immunotherapy. By contrast, antibodies targeting extracellular plasma membrane proteins may act as pathogenic effectors and often infer good responses to immunotherapy. Diagnosing these conditions and implementing treatment as early into the clinical course as possible ensures the best possible clinical outcomes. An adequate immunotherapy trial to assess maximum reversibility of symptoms, as assessed through objective functional measures, is crucial and can help to determine whether maintenance therapy is needed. C1 [Linnoila, Jenny] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Pittock, Sean J.] Mayo Clin, Coll Med, Dept Lab Med Pathol, Rochester, MN USA. [Pittock, Sean J.] Mayo Clin, Dept Neurol, Coll Med, Rochester, MN USA. RP Linnoila, J (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM Linnoila.Jenny@mgh.harvard.edu NR 104 TC 0 Z9 0 U1 4 U2 4 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0271-8235 EI 1098-9021 J9 SEMIN NEUROL JI Semin. Neurol. PD AUG PY 2016 VL 36 IS 4 BP 382 EP 396 DI 10.1055/s-0036-1585453 PG 15 WC Clinical Neurology SC Neurosciences & Neurology GA DW8RJ UT WOS:000383922900013 PM 27643908 ER PT J AU De Clercq, DJH Tavernier, J Lievens, S Van Calenbergh, S AF De Clercq, Dries J. H. Tavernier, Jan Lievens, Sam Van Calenbergh, Serge TI Chemical Dimerizers in Three-Hybrid Systems for Small Molecule-Target Protein Profiling SO ACS CHEMICAL BIOLOGY LA English DT Review ID FRAGMENT COMPLEMENTATION ASSAYS; REGULATED GENE-EXPRESSION; DIMERIZATION IN-VIVO; COVALENT TMP-TAG; DRUG DISCOVERY; DIHYDROFOLATE-REDUCTASE; SYNTHETIC LIGANDS; DEXAMETHASONE-METHOTREXATE; SACCHAROMYCES-CEREVISIAE; TRANSCRIPTIONAL CONTROL AB The identification of the molecular targets and mechanisms underpinning the beneficial or detrimental effects of small-molecule leads and drugs constitutes a crucial aspect of current drug discovery. Over the last two decades, three-hybrid (3H) systems have progressively taken an important position in the armamentarium of small molecule-target protein profiling technologies. Yet, a prerequisite for successful 3H analysis is the availability of appropriate chemical inducers of dimerization. Herein, we present a comprehensive and critical overview of the chemical dimerizers specifically applied in both yeast and mammalian three-hybrid systems for small molecule-target protein profiling within the broader scope of target deconvolution and drug discovery. Furthermore, examples and alternative suggestions for typical components of chemical dimerizers for 3H systems are discussed. As illustrated, more tools have become available that increase the sensitivity and efficiency of 3H-based screening platforms. Hence, it is anticipated that the great potential of 3H systems will further materialize in important contributions to drug discovery. C1 [De Clercq, Dries J. H.; Van Calenbergh, Serge] Univ Ghent, Fac Pharmaceut Sci, Med Chem Lab, B-9000 Ghent, Belgium. [Tavernier, Jan; Lievens, Sam] VIB, Dept Med Prot Res, B-9000 Ghent, Belgium. [Tavernier, Jan; Lievens, Sam] Univ Ghent, Dept Biochem, Fac Med & Hlth Sci, B-9000 Ghent, Belgium. [De Clercq, Dries J. H.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [De Clercq, Dries J. H.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Lievens, Sam] Orionis Biosci, B-9052 Ghent, Belgium. RP Van Calenbergh, S (reprint author), Univ Ghent, Fac Pharmaceut Sci, Med Chem Lab, B-9000 Ghent, Belgium.; Lievens, S (reprint author), VIB, Dept Med Prot Res, B-9000 Ghent, Belgium.; Lievens, S (reprint author), Univ Ghent, Dept Biochem, Fac Med & Hlth Sci, B-9000 Ghent, Belgium.; Lievens, S (reprint author), Orionis Biosci, B-9052 Ghent, Belgium. EM slievens@orionisbio.com; serge.vancalenbergh@ugent.be FU IUAP [P6/36]; ERC Advanced grant (CYRE) [340941]; Fund for Scientific Research-Flanders (FWO-V); Ghent University (BOF) FX J.T. was supported by a grant from IUAP P6/36, and is a recipient of an ERC Advanced grant (CYRE,340941). S.V.C. and J.T. received support from the Fund for Scientific Research-Flanders (FWO-V). D.D.C. obtained a Ph.D. grant from the special Research Fund of Ghent University (BOF). NR 131 TC 0 Z9 0 U1 13 U2 13 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 AUG PY 2016 VL 11 IS 8 BP 2075 EP 2090 DI 10.1021/acschembio.5b00811 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DT9UL UT WOS:000381847700001 PM 27267544 ER PT J AU Sundberg, TB Liang, YK Wu, HX Choi, HG Kim, ND Sim, T Johannessen, L Petrone, A Khor, B Graham, DB Latorre, IJ Phillips, AJ Schreiber, SL Perez, J Shamji, AF Gray, NS Xavier, RJ AF Sundberg, Thomas B. Liang, Yanke Wu, Huixian Choi, Hwan Geun Kim, Nam Doo Sim, Taebo Johannessen, Liv Petrone, Adam Khor, Bernard Graham, Daniel B. Latorre, Isabel J. Phillips, Andrew J. Schreiber, Stuart L. Perez, Jose Shamji, Alykhan F. Gray, Nathanael S. Xavier, Ramnik J. TI Development of Chemical Probes for Investigation of Salt-Inducible Kinase Function in Vivo SO ACS CHEMICAL BIOLOGY LA English DT Article ID SIK2; MICE; PHOSPHORYLATION; INFLAMMATION; MACROPHAGES; HOMEOSTASIS; ADIPOCYTES; CANCER; HDAC4; CELLS AB Salt-inducible kinases (SIKs) are promising therapeutic targets for modulating cytokine responses during innate immune activation. The study of SIK inhibition in animal models of disease has been limited by the lack of selective small-molecule probes suitable for modulating SIK function in vivo. We used the pan-SIK inhibitor HG-9-91-01 as a starting point to develop improved analogs, yielding a novel probe 5 (YKL-05-099) that displays increased selectivity for SIKs versus other kinases and enhanced pharmacokinetic properties. Well-tolerated doses of YKL-05-099 achieve free serum concentrations above its IC50 for SIK2 inhibition for >16 h and reduce phosphorylation of a known SIK substrate in vivo. While in vivo active doses of YKL-05-099 recapitulate the effects of SIK inhibition on inflammatory cytokine responses, they did not induce metabolic abnormalities observed in Sik2 knockout mice. These results identify YKL-05-099 as a useful probe to investigate SIK function in vivo and further support the development of SIK inhibitors for treatment of inflammatory disorders. C1 [Sundberg, Thomas B.; Petrone, Adam; Phillips, Andrew J.; Perez, Jose] Broad Inst, Ctr Dev Therapeut, Cambridge, MA 02142 USA. [Liang, Yanke; Choi, Hwan Geun; Johannessen, Liv; Gray, Nathanael S.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Liang, Yanke; Choi, Hwan Geun; Johannessen, Liv; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Wu, Huixian; Schreiber, Stuart L.; Shamji, Alykhan F.] Broad Inst, Ctr Sci Therapeut, Cambridge, MA 02142 USA. [Kim, Nam Doo] Daegu Gyeongbuk Med Innovat Fdn, Daegu 41061, South Korea. [Sim, Taebo] Korea Inst Sci & Technol, Chem Kinom Res Ctr, Seoul 136791, South Korea. [Khor, Bernard; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Graham, Daniel B.; Latorre, Isabel J.; Xavier, Ramnik J.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Graham, Daniel B.] Harvard Med Sch, Dept Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Schreiber, Stuart L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Schreiber, Stuart L.] Howard Hughes Med Inst, Cambridge, MA 02142 USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. RP Gray, NS (reprint author), Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.; Gray, NS (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.; Xavier, RJ (reprint author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.; Xavier, RJ (reprint author), Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.; Xavier, RJ (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.; Xavier, RJ (reprint author), Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. EM Nathanael_Gray@DFCI.HARVARD.EDU; xavier@molbio.mgh.harvard.edu FU National Institutes of Health [K08DK104021, U01DK062432, P30DK043351, R01AI095499]; Michael J. Fox Foundation for Parkinson's Research; Claudia Adams Barr Program for Innovative Cancer Research; Crohn's AMP; Colitis Foundation of America [500229]; Leona M. and Harry B. Helmsley Charitable Trust [500203] FX Research reported in this publication was supported by funding from the National Institutes of Health Grants K08DK104021 (B.K.), U01DK062432 and P30DK043351 (R.J.X.), and R01AI095499 (N.S.G.); Michael J. Fox Foundation for Parkinson's Research (N.S.G); Claudia Adams Barr Program for Innovative Cancer Research (N.S.G); Crohn's & Colitis Foundation of America Grant 500229 (to R.J.X.); and The Leona M. and Harry B. Helmsley Charitable Trust Grant 500203 (to S.L.S. and R.J.X.). S.L.S. is an Investigator of the Howard Hughes Medical Institute. NR 21 TC 1 Z9 1 U1 6 U2 6 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 AUG PY 2016 VL 11 IS 8 BP 2105 EP 2111 DI 10.1021/acschembio.6b00217 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DT9UL UT WOS:000381847700004 PM 27224444 ER PT J AU Surdel, MC Dutter, BF Sulikowski, GA Skaar, EP AF Surdel, Matthew C. Dutter, Brendan F. Sulikowski, Gary A. Skaar, Eric P. TI Bacterial Nitric Oxide Synthase Is Required for the Staphylococcus aureus Response to Heme Stress SO ACS INFECTIOUS DISEASES LA English DT Article DE Staphylococcus aureus; heme stress response; nitric oxide synthase; small-molecule optimization ID US HOSPITALS; INFECTIONS; TOXICITY; BIOSYNTHESIS; VIRULENCE; IRON; ACTIVATION; MOLECULE; SYSTEM; GENE AB Staphylococcus aureus is a pathogen that causes significant morbidity and mortality worldwide. Within the vertebrate host, S. aureus requires heme as a nutrient iron source and as a cofactor for multiple cellular processes. Although required for pathogenesis, excess heme is toxic. S. aureus employs a two-component system, the heme sensor system (HssRS), to sense and protect against heme toxicity. Upon activation, HssRS induces the expression of the heme-regulated transporter (HrtAB), an efflux pump that alleviates heme toxicity. The ability to sense and respond to heme is critical for the pathogenesis of numerous Gram-positive organisms, yet the mechanism of heme sensing remains unknown. Compound '3981 was identified in a high-throughput screen as an activator of staphylococcal HssRS that triggers HssRS independently of heme accumulation. '3981 is toxic to S. aureus; however, derivatives of '3981 were synthesized that lack toxicity while retaining HssRS activation, enabling the interrogation of the heme stress response without confounding toxic effects of the parent molecule. Using '3981 derivatives as probes of the heme stress response, numerous genes required for '3981-induced activation of HssRS were uncovered. Specifically, multiple genes involved in the production of nitric oxide were identified, including the gene encoding bacterial nitric oxide synthase (bNOS). bNOS protects S. aureus from oxidative stress imposed by heme. Taken together, this work identifies bNOS as crucial for the S. aureus heme stress response, providing evidence that nitric oxide synthesis and heme sensing are intertwined. C1 [Surdel, Matthew C.; Skaar, Eric P.] Vanderbilt Univ, Med Ctr, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA. [Dutter, Brendan F.; Sulikowski, Gary A.] Vanderbilt Univ, Dept Chem, Vanderbilt Inst Chem Biol, Nashville, TN 37232 USA. [Skaar, Eric P.] US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville, TN 37212 USA. RP Skaar, EP (reprint author), Vanderbilt Univ, Med Ctr, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA.; Skaar, EP (reprint author), US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville, TN 37212 USA. EM eric.skaar@vanderbilt.edu FU National Institute of General Medical Studies for the Vanderbilt Medical-Scientist Training Program [T32 GM07347, R01AI069233, R01AI073843, T32GM065086] FX We thank members of the E.P.S laboratory for their critical reading of the manuscript. The reagents were provided by the Network on Antimicrobial Resistance in Staphylococcus aureus for distribution by BEI Resources, Nebraska Transposon Mutant Library Screening Array, NR-48501. This work was supported by Public Health Service award T32 GM07347 from the National Institute of General Medical Studies for the Vanderbilt Medical-Scientist Training Program (M.C.S.), R01AI069233 (M.C.S. and E.P.S), R01AI073843 (M.C.S. and E.P.S.), and T32GM065086 (B.F.D.). NR 37 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 2373-8227 J9 ACS INFECT DIS JI ACS Infect. Dis. PD AUG PY 2016 VL 2 IS 8 BP 572 EP 578 DI 10.1021/acsinfecdis.6b00081 PG 7 WC Chemistry, Medicinal; Infectious Diseases SC Pharmacology & Pharmacy; Infectious Diseases GA DT6HI UT WOS:000381584900006 PM 27626297 ER PT J AU Abuelezam, NN McCormick, AW Fussell, T Afriyie, AN Wood, R DeGruttola, V Freedberg, KA Lipsitch, M Seage, GR AF Abuelezam, Nadia N. McCormick, Alethea W. Fussell, Thomas Afriyie, Abena N. Wood, Robin DeGruttola, Victor Freedberg, Kenneth A. Lipsitch, Marc Seage, George R., III TI Can the Heterosexual HIV Epidemic be Eliminated in South Africa Using Combination Prevention? A Modeling Analysis SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE acquired immunodeficiency syndrome; agent-based models; HIV; human immunodeficiency virus; mathematical modeling; South Africa ID RANDOMIZED CONTROLLED-TRIAL; SUB-SAHARAN AFRICA; ANTIRETROVIRAL THERAPY; COST-EFFECTIVENESS; MALE CIRCUMCISION; CAUSAL INFERENCE; PREEXPOSURE PROPHYLAXIS; CLINICAL IMPACT; COTE-DIVOIRE; INFECTION AB Little is known about how combining efficacious interventions for human immunodeficiency virus (HIV) prevention could lead to HIV elimination. We used an agent-based simulation model, the HIV calibrated dynamic model, to assess the potential for HIV elimination in South Africa. We examined several scenarios (from continuation of the current status quo to perfect achievement of targets) with differing combinations of male condom use, adult male circumcision, HIV testing, and early antiretroviral therapy (ART). We varied numerous parameters, including the proportion of adult males circumcised, the frequency of condom use during sex acts, acceptance of HIV testing, linkage to health care, criteria for ART initiation, ART viral suppression rates, and loss to follow-up. Maintaining current levels of combination prevention would lead to increasing HIV incidence and prevalence in South Africa, while the perfect combination scenario was projected to eliminate HIV on a 50-year time scale from 2013 to 2063. Perfecting testing and treatment, without changing condom use or circumcision rates, resulted in an 89% reduction in HIV incidence but not elimination. Universal adult male circumcision alone resulted in a 21% incidence reduction within 20 years. Substantial decreases in HIV incidence are possible from sufficient uptake of both primary prevention and ART, but with continuation of the status quo, HIV elimination in South Africa is unlikely within a 50-year time scale. C1 [Abuelezam, Nadia N.; McCormick, Alethea W.; Fussell, Thomas; Afriyie, Abena N.; Lipsitch, Marc; Seage, George R., III] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. [Wood, Robin] Univ Cape Town, Inst Infect Dis & Mol Med, Desmond Tutu HIV Ctr, Cape Town, South Africa. [DeGruttola, Victor] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Freedberg, Kenneth A.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Freedberg, Kenneth A.] Harvard Univ, Ctr AIDS Res, Cambridge, MA 02138 USA. [Freedberg, Kenneth A.] Harvard TH Chan Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Lipsitch, Marc] Harvard TH Chan Sch Publ Hlth, Ctr Communicable Dis Dynam, Boston, MA USA. [Lipsitch, Marc] Harvard TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA USA. RP Abuelezam, NN (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM nna465@mail.harvard.edu FU National Institutes of Health from the National Institute of Allergy and Infectious Diseases [R01-AI-058736, T32-AI-007535, T32-AI-007433]; National Institute of Mental Health [R01-MH-087328]; National Institute of General Medical Sciences [R01-GM-11652] FX This study was funded by the National Institutes of Health (grants R01-AI-058736, T32-AI-007535, and T32-AI-007433 from the National Institute of Allergy and Infectious Diseases; grant R01-MH-087328 from the National Institute of Mental Health; and grant R01-GM-11652 from the National Institute of General Medical Sciences). NR 61 TC 0 Z9 0 U1 4 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD AUG 1 PY 2016 VL 184 IS 3 BP 239 EP 248 DI 10.1093/aje/kwv344 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DV8HG UT WOS:000383177500010 PM 27416841 ER PT J AU Dinkler, JM Sugar, CA Escarce, JJ Ong, MK Mangione, CM AF Dinkler, John M. Sugar, Catherine A. Escarce, Jose J. Ong, Michael K. Mangione, Carol M. TI Does Age Matter? Association Between Usual Source of Care and Hypertension Control in the US Population: Data From NHANES 2007-2012 SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE age; blood pressure; hypertension; usual source of care ID BLOOD-PRESSURE; UNITED-STATES; ENDOTHELIAL DYSFUNCTION; NATIONAL-HEALTH; ADULTS; PREVENTION; IMPUTATION; PHYSICIAN; PATTERNS; SERVICES AB The positive role of having a usual source of care (USOC) on the receipt of preventative services is known. However, associations between USOC and hypertension control and the differential association across age groups is unknown in the US population. We used data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2012. Multivariable logistic regression was used to evaluate the association between having a USOC and hypertension control. The differential effect of USOC on hypertension control by age was assessed using predicted marginal effects across age groups in the multivariable logistic model. In adjusted analyses, those with a USOC had higher odds of hypertension control (odds ratio = 3.89, 95% confidence interval (CI): 2.15-6.98). The marginal effect of having a USOC is associated with a 30 percentage point higher probability of controlled blood pressure compared to those without a USOC (marginal probability = 0.30, 95% CI: 0.19-0.41). The marginal effect of USOC on hypertension control varied by age groups, with a statistically significantly lower marginal effect of USOC on hypertension seen among those older than 74 years of age (marginal probability = 0.27, 95% CI: 0.18-0.36) and younger than 35 years of age (marginal probability = 0.23, 95% CI: 0.14-0.33). Having a USOC is significantly associated with improved hypertension control in the US population. The variation in the association across age groups has important implications in targeting age-specific antihypertensive strategies to reduce the burden of hypertension in the US population. C1 [Dinkler, John M.] Univ Calif Los Angeles, Dept Med, Div Cardiol, Los Angeles, CA 90024 USA. [Dinkler, John M.; Escarce, Jose J.; Mangione, Carol M.] UCLA Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA 90024 USA. [Sugar, Catherine A.] UCLA Fielding Sch Publ Hlth, Dept Biostat, Los Angeles, CA USA. [Escarce, Jose J.; Ong, Michael K.; Mangione, Carol M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Ong, Michael K.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Dinkler, JM (reprint author), Univ Calif Los Angeles, Dept Med, Div Cardiol, Los Angeles, CA 90024 USA.; Dinkler, JM (reprint author), UCLA Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA 90024 USA. EM jdinkler@mednet.ucla.edu FU National Institutes of Health [T32HL007895-16] FX Dr Dinkler receives grant funding from the National Institutes of Health (T32HL007895-16). NR 37 TC 1 Z9 1 U1 4 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0895-7061 EI 1941-7225 J9 AM J HYPERTENS JI Am. J. Hypertens. PD AUG PY 2016 VL 29 IS 8 BP 934 EP 940 DI 10.1093/ajh/hpw010 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DV8HQ UT WOS:000383178500006 PM 26884134 ER PT J AU Ho, AK Bartels, CM Thorpe, CT Pandhi, N Smith, MA Johnson, HM AF Ho, Aaron K. Bartels, Christie M. Thorpe, Carolyn T. Pandhi, Nancy Smith, Maureen A. Johnson, Heather M. TI Achieving Weight Loss and Hypertension Control Among Obese Adults: A US Multidisciplinary Group Practice Observational Study SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE blood pressure; hypertension; obesity; primary care; weight management ID BODY-MASS INDEX; HIGH BLOOD-PRESSURE; SCIENTIFIC STATEMENT; ADMINISTRATIVE DATA; MORTALITY RISK; YOUNG-ADULTS; COMMITTEE; EDUCATION; OVERWEIGHT; MANAGEMENT AB Among adults with hypertension, obesity independently contributes to cardiovascular disease. Weight loss and hypertension control are critical to reduce cardiovascular events. The purpose of this study was to evaluate rates and predictors of achieving weight loss among adults who achieved hypertension control within 1 year of developing incident hypertension. Retrospective electronic health record analysis was performed of a parts per thousand yen18 year olds with a body mass index a parts per thousand yen30.0kg/m(2), who received regular primary care from 2008 to 2011 and achieved hypertension control. Exclusions were less than 60 days follow-up, prior hypertension diagnosis, prior antihypertensive prescription, or pregnancy. The primary outcome was clinically significant weight loss (a parts per thousand yen5kg); the secondary outcome was modest (2.0-4.9kg) weight loss. Multinomial logistic regression identified predictors of achieving weight loss (a parts per thousand yen5 or 2.0-4.9kg) compared to no significant weight loss (< 2kg). Of the 2,906 obese patients who achieved hypertension control, 72% (n = 2,089) did not achieve at least 2.0kg weight loss. Overall, 12% (n = 351) achieved a parts per thousand yen5kg weight loss. Young adults (18-39 year olds; odds ratio (OR): 2.47, 95% confidence interval (CI): 1.63-3.47), middle-aged adults (40-59 year olds; OR: 2.32, 95% CI: 1.59-3.37), and patients prescribed antihypertensive medication (OR: 1.37, 95% CI: 1.07-1.76) were more likely to achieve clinically significant weight loss and hypertension control. Age remained a significant predictor for 2.0-4.9kg weight loss. Despite achieving hypertension control, the majority of obese patients did not achieve clinically significant weight loss. Effective weight loss interventions with dedicated hypertension treatment are needed to decrease cardiovascular events in this high-risk population. C1 [Ho, Aaron K.; Bartels, Christie M.; Johnson, Heather M.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Bartels, Christie M.; Pandhi, Nancy; Smith, Maureen A.; Johnson, Heather M.] Univ Wisconsin, Hlth Innovat Program, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Thorpe, Carolyn T.] Vet Affairs Pittsburgh Healthcare Syst, Hlth Serv Res & Dev, Pittsburgh, PA USA. [Thorpe, Carolyn T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. [Pandhi, Nancy; Smith, Maureen A.] Univ Wisconsin, Dept Family Med, Sch Med & Publ Hlth, Madison, WI USA. [Smith, Maureen A.] Univ Wisconsin, Dept Populat Hlth Sci, Sch Med & Publ Hlth, Madison, WI USA. [Smith, Maureen A.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI USA. RP Johnson, HM (reprint author), Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI 53706 USA.; Johnson, HM (reprint author), Univ Wisconsin, Hlth Innovat Program, Sch Med & Publ Hlth, Madison, WI 53706 USA. EM hm2@medicine.wisc.edu FU Clinical and Translational Science Award program, previously through the National Center for Research Resources (NCRR) [UL1RR025011]; National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) [U54TR000021]; National Heart, Lung, and Blood Institute of the NIH [K23HL112907]; University of Wisconsin (UW) Centennial Scholars Program of the University of Wisconsin School of Medicine and Public Health; National Institute of Arthritis and Musculoskeletal and Skin Diseases of the NIH [K23AR062381]; National Institute on Aging of the NIH [K08AG029527] FX The authors gratefully acknowledge Katie Ronk, BS and Patrick Ferguson, MPH for data preparation and Jamie LaMantia, BS and Colleen Brown, BA for manuscript preparation. This original research was supported by the Clinical and Translational Science Award program, previously through the National Center for Research Resources (NCRR - UL1RR025011) and now by the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) under award number U54TR000021. H.M.J. is supported by the National Heart, Lung, and Blood Institute of the NIH (K23HL112907) and also by the University of Wisconsin (UW) Centennial Scholars Program of the University of Wisconsin School of Medicine and Public Health. C.M.B. is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the NIH (K23AR062381). N.P. is supported by the National Institute on Aging of the NIH (K08AG029527). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Additional funding for this project was provided by the UW Health Innovation Program and the UW School of Medicine and Public Health from The Wisconsin Partnership Program. Some preliminary findings reported in this manuscript were presented in poster form at the American Heart Association 2014 Annual Scientific Sessions in Chicago, IL on 15-19 November 2014. NR 39 TC 1 Z9 1 U1 3 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0895-7061 EI 1941-7225 J9 AM J HYPERTENS JI Am. J. Hypertens. PD AUG PY 2016 VL 29 IS 8 BP 984 EP 991 DI 10.1093/ajh/hpw020 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DV8HQ UT WOS:000383178500012 PM 26917445 ER PT J AU Ramey, LN McInnis, KC Palmer, WE AF Ramey, Lindsay N. McInnis, Kelly C. Palmer, William E. TI Femoral Neck Stress Fracture: Can MRI Grade Help Predict Return-to-Running Time? SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE femoral neck stress fracture; magnetic resonance imaging; rehabilitation; hip; stress fractures ID RISK-FACTORS; INJURIES; BONE; MANAGEMENT; TRACK; PLAY; CLASSIFICATION; AGE; HIP AB Background: Limited research is available regarding return-to-running (RTR) time after femoral neck stress fractures. While studies have shown the prognostic value of image-based grading scales for stress fractures at other sites, few have included femoral neck stress fractures. Purpose: To determine if the grade of femoral neck stress fractures based on magnetic resonance imaging (MRI) characteristics correlates with RTR time. Study Design: Cohort study; Level of evidence, 3. Methods: This study included 24 patients (mean age, 32.9 years; range, 18-51 years) who were diagnosed with 27 femoral neck stress fractures by MRI from 2009 to 2015 at a single sports medicine clinic. All fractures were compression sided and were treated nonoperatively. Charts were reviewed for patient demographics and RTR time. Images were graded from 1 to 4 using the Arendt stress fracture severity scale. Statistical analysis was performed using survival analysis and Cox proportional hazard model to compare the RTR time between grades. Cox regression was repeated, adjusted for age, bone mineral density (BMD), and body mass index (BMI). Results: The mean (standard error of the mean) RTR time in weeks for patients with fractures graded 1 to 4 was 7.4 +/- 2.7 (range, 4-11), 13.8 +/- 3.8 (range, 6-21), 14.7 +/- 3.5 (range, 8.5-24), and 17.5 +/- 3.4 (range, 10-32), respectively. Survival analysis indicated that there was a statistically significant effect of fracture grade on RTR time (P = .0065). The Cox model indicated a statistically significant difference in RTR time between grades 1 and 2 (P = .036), 1 and 3 (P = .014), and 1 and 4 (P = .002). The unadjusted hazard ratio was significant (P = .037). There were no statistically significant differences between the remaining grades (P = .82 for grades 2 and 3, P = .37 for grades 2 and 4, and P = .31 for grades 3 and 4). Age (P = .71) and BMD (P = .81) did not have an effect on RTR time. The hazard ratio remained significant (P = .05) after adjusting for age and BMD. BMI tended to have an effect on RTR time (P = .09). After adding BMI to the adjustment, the hazard ratio decreased in significance (P = .13), although sample size also decreased. Conclusion: Grade 2 to 4 femoral neck stress fractures require longer RTR time than do grade 1 injuries. Patients with lower BMI tend to require a longer RTR time. C1 [Ramey, Lindsay N.; McInnis, Kelly C.; Palmer, William E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ramey, Lindsay N.; McInnis, Kelly C.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Charlestown, MA USA. [Ramey, Lindsay N.; McInnis, Kelly C.; Palmer, William E.] Harvard Med Sch, Cambridge, MA USA. [McInnis, Kelly C.] Massachusetts Gen Hosp, Div Orthoped, Boston, MA 02114 USA. [Palmer, William E.] Massachusetts Gen Hosp, Div Radiol, Boston, MA 02114 USA. RP Ramey, LN (reprint author), Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, 300 First Ave, Boston, MA 02129 USA. EM lnr8t@virginia.edu NR 30 TC 1 Z9 1 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 EI 1552-3365 J9 AM J SPORT MED JI Am. J. Sports Med. PD AUG PY 2016 VL 44 IS 8 BP 2122 EP 2129 DI 10.1177/0363546516648319 PG 8 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA DU4UM UT WOS:000382208100029 PM 27261475 ER PT J AU Amri, R Klos, CL Bordeianou, L Berger, DL AF Amri, Ramzi Klos, Coen L. Bordeianou, Liliana Berger, David L. TI The prognostic value of lymph node ratio in colon cancer is independent of resection length SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Colon cancer; Lymph node ratio; Resection length; Outcomes; Survival; Disease-free survival ID COMPLETE MESOCOLIC EXCISION; COLORECTAL-CANCER; SURVIVAL; SURGERY; LIGATION; ADENOCARCINOMA; NUMBER AB BACKGROUND: Lymph node ratio (LNR), the ratio of tumor-positive lymph nodes (+LN) to the total number of resected lymph nodes (rLN), predicts recurrence and survival in colon cancer. Variations in colonic resection length (RL) may influence rLN, +LN, or both, thereby potentially impacting LNR and its prognostic value in colon cancer. METHODS: All colon cancer patients treated surgically at our center from 2004 to 2011 were included in an institutional review board-approved data repository (n = 1,039). RESULTS: Larger RL was associated with increased rLN (rho = .22; P < .001) but not with +LN (P = .21). In node-positive patients (n = 411), RL-adjusted LNR had weaker correlations with death (rho = .338 vs .373, both P < .001) or metastatic disease (rho = .303 vs .345; both P < .001) and a smaller area under the curve (death: .695 vs .715, metastasis: .675 vs .699). Findings were similar in segmental, extended segmental, and total colectomy subgroups. CONCLUSIONS: Provided that resections are performed following standard oncologic principles, our analysis shows that RL does not significantly impact the prognostic value of LNR in colon cancer. Correcting LNR for RL seems redundant and may even act as noise distorting LNR values. (C) 2016 Elsevier Inc. All rights reserved. C1 [Amri, Ramzi; Bordeianou, Liliana; Berger, David L.] Harvard Med Sch, Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, 15 Parkman St,WAC 460, Boston, MA 02114 USA. [Klos, Coen L.] Washington Univ, Sch Med, Dept Surg, Sect Colon & Rectal Surg, St Louis, MO 63110 USA. RP Berger, DL (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, 15 Parkman St,WAC 460, Boston, MA 02114 USA. EM dberger@mgh.harvard.edu OI Amri, Ramzi/0000-0001-7416-6650 FU Harvard Catalyst\The Harvard Clinical and Translational Science Center (National Center for Research Resources, National Institutes of Health) [8UL1TR000170-05]; Harvard Catalyst\The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [8UL1TR000170-05]; Harvard Catalyst\The Harvard Clinical and Translational Science Center (Harvard University and its affiliated academic health care centers); Dutch Cancer Society; Dutch Digestive Society; Amsterdam University Funds; Fulbright Foundation FX This work was conducted with support from Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 8UL1TR000170-05 and financial contributions from Harvard University and its affiliated academic health care centers). This work was also supported by the Dutch Cancer Society, the Dutch Digestive Society, the Amsterdam University Funds, and the Fulbright Foundation. R.A. has received funding from the Fulbright Foundation, the Dutch Cancer Society, the Dutch Digestive Society, and Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 8UL1TR000170-05 and financial contributions from Harvard University and its affiliated academic health care centers). NR 23 TC 2 Z9 2 U1 2 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 EI 1879-1883 J9 AM J SURG JI Am. J. Surg. PD AUG PY 2016 VL 212 IS 2 BP 251 EP 257 DI 10.1016/j.amjsurg.2015.10.037 PG 7 WC Surgery SC Surgery GA DU5EF UT WOS:000382234300010 PM 27156798 ER PT J AU Jones, CE Hollis, RH Wahl, TS Oriel, BS Itani, KMF Morris, MS Hawn, MT AF Jones, Caroline E. Hollis, Robert H. Wahl, Tyler S. Oriel, Brad S. Itani, Kamal M. F. Morris, Melanie S. Hawn, Mary T. TI Transitional care interventions and hospital readmissions in surgical populations: a systematic review SO AMERICAN JOURNAL OF SURGERY LA English DT Review DE Transitional care; Hospital readmission; Health services research; Population health; Patient-centered care; Patient discharge ID MEDICARE BENEFICIARIES; POSTOPERATIVE READMISSION; 30-DAY READMISSION; COLORECTAL-CANCER; RANDOMIZED-TRIAL; SURGERY PATIENTS; GENERAL-SURGERY; FOLLOW-UP; QUALITY; PROGRAM AB BACKGROUND: Despite hospital readmission being a targeted quality metric, few studies have focused on the surgical patient population. We performed a systematic review of transitional care interventions and their effect on hospital readmissions after surgery. DATA SOURCES: PubMed was searched for studies evaluating transitional care interventions in surgical populations within the years 1995 to 2015. Of 3,527 abstracts identified, 3 randomized controlled trials and 7 observational cohort studies met inclusion criteria. CONCLUSIONS: Discharge planning programs reduced readmissions by 11.5% (P = .001), 12.5% (P = .04), and 23% (P = .26). Patient education interventions reduced readmissions by 14% (P = .28) and 23.5%(P < .05). Primary care follow- up reduced readmissions by 8.3% for patients after high-risk surgeries (P < .001). Home visits reduced readmissions by 7.69% (P = .023) and 4% (P = .161), respectively. Therefore, improving discharge planning, patient education, and follow- up communication may reduce readmissions. Published by Elsevier Inc. C1 [Jones, Caroline E.; Hollis, Robert H.; Wahl, Tyler S.; Morris, Melanie S.] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA. [Jones, Caroline E.; Hollis, Robert H.; Wahl, Tyler S.; Morris, Melanie S.] Birmingham Vet Adm Hosp, Birmingham, AL USA. [Oriel, Brad S.; Itani, Kamal M. F.] VA Boston Hlth Care Syst, Boston, MA USA. [Oriel, Brad S.; Itani, Kamal M. F.] Tufts Univ, Sch Med, Dept Surg, Boston, MA 02111 USA. [Hawn, Mary T.] Stanford Univ, Dept Surg, Palo Alto, CA 94304 USA. [Hawn, Mary T.] VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA. RP Hawn, MT (reprint author), Stanford Univ, Dept Surg, Palo Alto, CA 94304 USA.; Hawn, MT (reprint author), VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA. EM mhawn@stanford.edu FU National Institutes of Health [T32 CA091078-13]; Agency for Healthcare Research and Quality grant [T32 4T32HS013852-13] FX The opinions expressed are those of the authors and do not necessarily reflect those of the Department of Veterans Affairs of the United States Government. R. H. is supported by grant T32 CA091078-13 from the National Institutes of Health. T. W. is supported by the Agency for Healthcare Research and Quality grant T32 4T32HS013852-13. NR 42 TC 0 Z9 0 U1 7 U2 7 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 EI 1879-1883 J9 AM J SURG JI Am. J. Surg. PD AUG PY 2016 VL 212 IS 2 BP 327 EP 335 DI 10.1016/j.amjsurg.2016.04.004 PG 9 WC Surgery SC Surgery GA DU5EF UT WOS:000382234300020 PM 27353404 ER PT J AU Di Giacomo, G Golijanin, P Sanchez, G Provencher, MT AF Di Giacomo, Giovanni Golijanin, Petar Sanchez, George Provencher, Matthew T. TI Radiographic Analysis of the Hill-Sachs Lesion in Anteroinferior Shoulder Instability After First-Time Dislocations SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article ID RECURRENT ANTERIOR DISLOCATION; HUMERAL HEAD; DEFECTS; FAILURE; REPAIRS; TRACK AB Purpose: To identify the relation between the Hill-Sachs (H-S) angle and arm position at the time of the initial dislocation, and to see if this correlates with the glenoid track. Methods: A total of 102 patients (89 male patients, 87.2%), with a mean age of 32 years (range, 17 to 38 years), were divided into 2 groups, abduction (ABD) and adduction (ADD), dependent on the position of the arm at the time of the instability event. All patients were evaluated with bilateral computed tomography scans (3-dimensional) to define the H-S position on the glenoid track and to measure the H-S angle. One-way analysis of variance was used to compare the H-S angle between the 2 groups. Results: Dislocation occurred in ABD in 45 patients (44.1%) and in ADD in 57 (55.9%). The H-S angle was 32.4 degrees +/- 4.7 degrees in the ABD group versus 16.1 degrees +/- 2.9 degrees in the ADD group. All patients' injuries were "on-track" glenoid injuries in both groups. Conclusions: This study identified a difference in the H-S angle relative to arm position at the time of initial dislocation. Patients whose injury occurred in the ABD position showed a higher H-S angle, leading to an increased risk of engagement, because the long axis of the H-S lesion is parallel to the glenoid in a position of function. Thus arm position at the time of the initial instability event may be a risk factor for engagement and higher risk of recurrence. C1 [Di Giacomo, Giovanni] Concordia Hosp Special Surg, Dept Orthopaed Surg, Rome, Italy. [Golijanin, Petar] Geisel Sch Med Dartmouth, Hanover, NH USA. [Sanchez, George; Provencher, Matthew T.] Massachusetts Gen Hosp, Sports Med Serv, Boston, MA 02114 USA. RP Provencher, MT (reprint author), MGH Sports Med Ctr, Sports Med Serv, 175 Cambridge St,Fourth Floor, Boston, MA 02114 USA. EM MattProvencher@gmail.com FU Arthrex; American Orthopaedic Society for Sports Medicine/Arthroscopy Association of North America FX The authors report the following potential conflict of interest or source of funding: G.D.G. receives support from Arthrex. M.T.P. receives support from American Orthopaedic Society for Sports Medicine/Arthroscopy Association of North America. No money. Arthrex/Joint Restoration Foundation. Peer Reviewed Orthopaedic Research Program. Shoulder instability database. Arthrex. Suture washer and pec button. Elsevier. Arthroscopy journal, shoulder instability textbook, and rehabilitation textbook. NR 21 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-8063 EI 1526-3231 J9 ARTHROSCOPY JI Arthroscopy PD AUG PY 2016 VL 32 IS 8 BP 1509 EP 1514 DI 10.1016/j.arthro.2016.01.022 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA DV8ZT UT WOS:000383229800009 PM 27039213 ER PT J AU Hansen, KJ Favreau, JT Guyette, JP Tao, ZW Coffin, ST Cunha-Gavidia, A D'Amore, B Perreault, LR Fitzpatrick, JP DeMartino, A Gaudette, GR AF Hansen, Katrina J. Favreau, John T. Guyette, Jacques P. Tao, Ze-Wei Coffin, Spencer T. Cunha-Gavidia, Anny D'Amore, Brian Perreault, Luke R. Fitzpatrick, John P. DeMartino, Angelica Gaudette, Glenn R. TI Functional Effects of Delivering Human Mesenchymal Stem Cell-Seeded Biological Sutures to an Infarcted Heart SO BIORESEARCH OPEN ACCESS LA English DT Article DE biomaterials; cardiology; stem cells; tissue engineering ID ACUTE MYOCARDIAL-INFARCTION; LEFT-VENTRICULAR FUNCTION; MARROW MONONUCLEAR-CELLS; PHASE CORRELATION; RANDOMIZED-TRIAL; CLINICAL-TRIAL; INTRACORONARY; FAILURE; TRANSPLANTATION; SURVIVAL AB Stem cell therapy has the potential to improve cardiac function after myocardial infarction (MI); however, existing methods to deliver cells to the myocardium, including intramyocardial injection, suffer from low engraftment rates. In this study, we used a rat model of acute MI to assess the effects of human mesenchymal stem cell (hMSC)-seeded fibrin biological sutures on cardiac function at 1 week after implant. Biological sutures were seeded with quantum dot (Qdot)-loaded hMSCs for 24 h before implantation. At 1 week postinfarct, the heart was imaged to assess mechanical function in the infarct region. Regional parameters assessed were regional stroke work (RSW) and systolic area of contraction (SAC) and global parameters derived from the pressure waveform. MI (n = 6) significantly decreased RSW (0.026+/-0.011) and SAC (0.022+/-0.015) when compared with sham operation (RSW: 0.141+/-0.009; SAC: 0.166+/-0.005, n = 6) (p < 0.05). The delivery of unseeded biological sutures to the infarcted hearts did not change regional mechanical function compared with the infarcted hearts (RSW: 0.032+/-0.004, SAC: 0.037+/-0.008, n = 6). The delivery of hMSC-seeded sutures exerted a trend toward increase of regional mechanical function compared with the infarcted heart (RSW: 0.057+/-0.011; SAC: 0.051+/-0.014, n = 6). Global function showed no significant differences between any group (p > 0.05); however, there was a trend toward improved function with the addition of either unseeded or seeded biological suture. Histology demonstrated that Qdot-loaded hMSCs remained present in the infarcted myocardium after 1 week. Analysis of serial sections of Masson's trichrome staining revealed that the greatest infarct size was in the infarct group (7.0%+/-2.2%), where unseeded (3.8%+/-0.6%) and hMSC-seeded (3.7%+/-0.8%) suture groups maintained similar infarct sizes. Furthermore, the remaining suture area was significantly decreased in the unseeded group compared with that in the hMSC-seeded group (p < 0.05). This study demonstrated that hMSC-seeded biological sutures are a method to deliver cells to the infarcted myocardium and have treatment potential. C1 [Hansen, Katrina J.; Favreau, John T.; Guyette, Jacques P.; Tao, Ze-Wei; Coffin, Spencer T.; Cunha-Gavidia, Anny; D'Amore, Brian; Perreault, Luke R.; Fitzpatrick, John P.; DeMartino, Angelica; Gaudette, Glenn R.] Worcester Polytech Inst, Dept Biomed Engn, 60 Prescott St, Worcester, MA 01605 USA. [Guyette, Jacques P.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Tao, Ze-Wei] Univ Arkansas Med Sci, Dept Pharmaceut Sci, Little Rock, AR 72205 USA. RP Gaudette, GR (reprint author), Worcester Polytech Inst, Dept Biomed Engn, 60 Prescott St, Worcester, MA 01605 USA. EM gaudette@wpi.edu FU NHLBI NIH HHS [R01 HL115282] NR 39 TC 0 Z9 0 U1 4 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2164-7844 EI 2164-7860 J9 BIORESEARCH OPEN ACC JI BioResearch Open Access PD AUG PY 2016 VL 5 IS 1 BP 249 EP 260 DI 10.1089/biores.2016.0026 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DV9SR UT WOS:000383282500001 PM 27610271 ER PT J AU Warner, ET Ballman, KV Strand, C Boughey, JC Buzdar, AU Carey, LA Sikov, WM Partridge, AH AF Warner, Erica T. Ballman, Karla V. Strand, Carrie Boughey, Judy C. Buzdar, Aman U. Carey, Lisa A. Sikov, William M. Partridge, Ann H. TI Impact of race, ethnicity, and BMI on achievement of pathologic complete response following neoadjuvant chemotherapy for breast cancer: a pooled analysis of four prospective Alliance clinical trials (A151426) SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Race; Ethnicity; Body mass index; Pathologic complete response ID BODY-MASS INDEX; ADJUVANT CHEMOTHERAPY; CONSERVING SURGERY; RACIAL-DIFFERENCES; TUMOR BIOLOGY; WHITE WOMEN; STAGE-II; SURVIVAL; OUTCOMES; SUBTYPES AB Previous studies demonstrated poor response to neoadjuvant systemic therapy (NST) for breast cancer among black women and women who are overweight or obese, but this may be due to chemotherapy underdosing. We assessed associations of race, ethnicity, and body mass index (BMI) with pathologic complete response (pCR) in clinical trial populations. 1797 women enrolled in four NST trials (CALGB 40601, 40603; ACOSOG Z1041, Z1071) were included. Tumor subtypes were defined by estrogen receptor (ER) and HER2 status. Logistic regression generated odds ratios (OR) and 95 % confidence intervals (CI) for the associations of race, ethnicity, and BMI with in-breast pCR adjusting for subtype, study arm, lymph node status, tumor size, and tumor grade. 253 (14.1 %) were black, 199 (11.1 %) Hispanic, 520 (28.9 %) overweight, and 743 (41.4 %) obese. Compared to whites, Blacks and Hispanics were more likely to be obese and Blacks were more likely to have triple-negative cancer. pCR rates differed significantly by tumor subtype. In multivariate analyses, neither race (black vs white: OR 1.18, 95 % CI 0.85-1.62) nor ethnicity (Hispanic vs non-Hispanic; OR 1.30, 95 % CI 0.67-2.53) were significant predictors of pCR overall or by subtype. Overweight and obese women had lower pCR rates in ER+/HER2+, but higher pCR rates in ER-/HER2+ cancers. There was no difference in pCR according to race or ethnicity. Overall, there was no major difference in pCR rates by BMI. These findings suggest that pCR with optimally dosed NST is a function of tumor, rather than patient, biology. C1 [Warner, Erica T.] Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. [Ballman, Karla V.] Weill Cornell Med Coll, 402 East 67th St, New York, NY 10065 USA. [Strand, Carrie] Alliance Stat & Data Ctr, 1216 Second St SW, Rochester, MN 55902 USA. [Boughey, Judy C.] Mayo Clin, 200 1st St SW, Rochester, MN 55905 USA. [Buzdar, Aman U.] Univ Texas MD Anderson Canc Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA. [Carey, Lisa A.] Univ North Carolina Chapel Hill, Lineberger Comprehens Canc Ctr, 101 Manning Dr, Chapel Hill, NC 27514 USA. [Sikov, William M.] Brown Univ, Women & Infants Hosp Rhode Isl, 101 Dudley St, Providence, RI 02905 USA. [Sikov, William M.] Brown Univ, Alpert Med Sch, 101 Dudley St, Providence, RI 02905 USA. [Partridge, Ann H.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Partridge, Ann H.] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. RP Warner, ET (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM ewarner@mgh.harvard.edu FU National Cancer Institute of the National Institutes of Health [UG1CA189823, U10CA180790, U10CA180838, U10CA180858, U10CA180867]; NCI [K01CA188075] FX The authors would like to acknowledge Dr. Olwen Hahn for her contributions to the included studies. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under the Award Number UG1CA189823 (to the Alliance for Clinical Trials in Oncology NCORP Grant), U10CA180790, U10CA180838, U10CA180858, and U10CA180867. Dr. Warner was supported by NCI Grant K01CA188075. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The study sponsors had no role in study design, collection, analysis, and interpretation of data, writing the report, or the decision to submit the report for publication. Dr. Warner had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. NR 51 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD AUG PY 2016 VL 159 IS 1 BP 109 EP 118 DI 10.1007/s10549-016-3918-5 PG 10 WC Oncology SC Oncology GA DV3UA UT WOS:000382847800010 PM 27449492 ER PT J AU Vaz-Luis, I Lin, NU Keating, NL Barry, WT Lii, J Burstein, HJ Winer, EP Freedman, RA AF Vaz-Luis, Ines Lin, Nancy U. Keating, Nancy L. Barry, William T. Lii, Joyce Burstein, Harold J. Winer, Eric P. Freedman, Rachel A. TI Treatment of early-stage human epidermal growth factor 2-positive cancers among medicare enrollees: age and race strongly associated with non-use of trastuzumab SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Trastuzumab; Breast cancer; HER2-positive; SEER-medicare ID HER2-POSITIVE BREAST-CANCER; ADJUVANT CHEMOTHERAPY; RACIAL-DIFFERENCES; COMORBIDITY INDEX; OLDER PATIENTS; HEART-FAILURE; UNITED-STATES; FOLLOW-UP; THERAPY; WOMEN AB Adjuvant trastuzumab for human epidermal growth factor receptor-2 (HER2)-positive breast cancer is highly efficacious regardless of age. Recent data suggested that many older patients with HER2-positive disease do not receive adjuvant trastuzumab. Nevertheless, some of this 'under-treatment' may be clinically appropriate. We used Surveillance, Epidemiology and End Results (SEER)-Medicare data to identify patients aged aeyen 66 with stage aeyen Ib-III, HER2-positive breast cancer diagnosed during 2010-2011 (HER2 status available) who did not have a history of congestive heart failure. We described all systemic treatments received and sociodemographic and clinical characteristics associated with treatment patterns. Among 770 women 44.4 % did not receive trastuzumab, including 21.8 % who received endocrine therapy only, 6.3 % who received chemotherapy (+/- endocrine therapy) and 16.2 % who did not receive any systemic therapy. In addition to age and grade, race was strongly associated with non-use of trastuzumab (64.4 % of Non-Hispanic blacks vs. 43.6 % of whites did not receive trastuzumab, adjusted ORNon-Hispanic black vs. white = 3.14, 95 %CI = 1.38-7.17), and many patients with stage III disease did not receive trastuzumab. Further, 16.2 % of patients did not receive any systemic treatment and this occurred more frequently for black patients. Over 40 % of older patients with indication to receive adjuvant trastuzumab did not receive it and nearly 20 % of these patients did not receive any other treatment. Although treatment omission may be appropriate in some cases, we observed concerning differences in trastuzumab receipt, particularly for black women. Strategies to optimize care for older patients and to eliminate treatment disparities are urgently needed. C1 [Vaz-Luis, Ines; Lin, Nancy U.; Burstein, Harold J.; Winer, Eric P.; Freedman, Rachel A.] Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. [Keating, Nancy L.] Harvard Med Sch, Dept Hlth Care Policy, Boston, MA USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, 75 Francis St, Boston, MA 02115 USA. [Barry, William T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Lii, Joyce] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 75 Francis St, Boston, MA 02115 USA. RP Freedman, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM inesv_luis@dfci.harvard.edu; rafreedman@partners.org FU Fundacao para a Ciencia e Tecnologia [HMSP-ICS/0004/2011]; Dana-Farber Cancer Institute Friends Grant FX The study was supported by Fundacao para a Ciencia e Tecnologia (HMSP-ICS/0004/2011, Career Development Award) (to I Vaz-Luis) and Dana-Farber Cancer Institute Friends Grant (to R Freedman and I Vaz Luis). NR 37 TC 1 Z9 1 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD AUG PY 2016 VL 159 IS 1 BP 151 EP 162 DI 10.1007/s10549-016-3927-4 PG 12 WC Oncology SC Oncology GA DV3UA UT WOS:000382847800014 PM 27484879 ER PT J AU D'Souza, N Hashimoto, D Gurusamy, K Aggarwal, R AF D'Souza, N. Hashimoto, D. Gurusamy, K. Aggarwal, R. TI Are Patients Safe During Trainee Performed Surgery? A Meta-Analysis of Trainee versus Consultant Outcomes in Surgery SO BRITISH JOURNAL OF SURGERY LA English DT Meeting Abstract CT International Surgical Congress of the Association-of-Surgeons-of-Great-Britain-and-Ireland CY 2016 CL Belfast, IRELAND SP Assoc Surg Great Britain & Ireland C1 [D'Souza, N.] Wessex Deanery, Wessex, England. [Hashimoto, D.] Massachussets Gen Hosp, Boston, MA USA. [Gurusamy, K.] UCL Med Sch, London, England. [Aggarwal, R.] McGill Univ, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1323 EI 1365-2168 J9 BRIT J SURG JI Br. J. Surg. PD AUG PY 2016 VL 103 SU 6 SI SI MA 0057 BP 47 EP 47 PG 1 WC Surgery SC Surgery GA DV9VF UT WOS:000383289600134 ER PT J AU Incio, J Liu, H Suboj, P Chin, SM Chen, IX Pinter, M Ng, MR Nia, HT Grahovac, J Kao, S Babykutty, S Huang, YH Jung, K Rahbari, NN Han, XX Chauhan, VP Martin, JD Kahn, J Huang, PG Desphande, V Michaelson, J Michelakos, TP Ferrone, CR Soares, R Boucher, Y Fukumura, D Jain, RK AF Incio, Joao Liu, Hao Suboj, Priya Chin, Shan M. Chen, Ivy X. Pinter, Matthias Ng, Mei R. Nia, Hadi T. Grahovac, Jelena Kao, Shannon Babykutty, Suboj Huang, Yuhui Jung, Keehoon Rahbari, Nuh N. Han, Xiaoxing Chauhan, Vikash P. Martin, John D. Kahn, Julia Huang, Peigen Desphande, Vikram Michaelson, James Michelakos, Theodoros P. Ferrone, Cristina R. Soares, Raquel Boucher, Yves Fukumura, Dai Jain, Rakesh K. TI Obesity-Induced Inflammation and Desmoplasia Promote Pancreatic Cancer Progression and Resistance to Chemotherapy SO CANCER DISCOVERY LA English DT Article ID HIGH-FAT DIET; SUBTYPE AT1 RECEPTORS; TUMOR BLOOD-VESSELS; BODY-MASS INDEX; DUCTAL ADENOCARCINOMA; ANGIOTENSIN-II; ADIPOSE-TISSUE; STELLATE CELLS; SELECTIVE INHIBITOR; SIGNALING PATHWAYS AB It remains unclear how obesity worsens treatment outcomes in patients with pancreatic ductal adenocarcinoma (PDAC). In normal pancreas, obesity promotes inflammation and fibrosis. We found in mouse models of PDAC that obesity also promotes desmoplasia associated with accelerated tumor growth and impaired delivery/efficacy of chemotherapeutics through reduced perfusion. Genetic and pharmacologic inhibition of angiotensin-II type-1 receptor reverses obesity-augmented desmoplasia and tumor growth and improves response to chemotherapy. Augmented activation of pancreatic stellate cells (PSC) in obesity is induced by tumor-associated neutrophils (TAN) recruited by adipocyte-secreted IL1 beta. PSCs further secrete IL1 beta, and inactivation of PSCs reduces IL1 beta expression and TAN recruitment. Furthermore, depletion of TANs, IL1 beta inhibition, or inactivation of PSCs prevents obesity-accelerated tumor growth. In patients with pancreatic cancer, we confirmed that obesity is associated with increased desmoplasia and reduced response to chemotherapy. We conclude that cross-talk between adipocytes, TANs, and PSCs exacerbates desmoplasia and promotes tumor progression in obesity. SIGNIFICANCE : Considering the current obesity pandemic, unraveling the mechanisms underlying obesity- induced cancer progression is an urgent need. We found that the aggravation of desmoplasia is a key mechanism of obesity- promoted PDAC progression. Importantly, we discovered that clinically available antifi brotic/infl ammatory agents can improve the treatment response of PDAC in obese hosts. Cancer Discov; 6(8); 852-69. (C) 2016 AACR. C1 [Incio, Joao; Liu, Hao; Suboj, Priya; Chin, Shan M.; Chen, Ivy X.; Pinter, Matthias; Ng, Mei R.; Nia, Hadi T.; Grahovac, Jelena; Kao, Shannon; Babykutty, Suboj; Huang, Yuhui; Jung, Keehoon; Rahbari, Nuh N.; Han, Xiaoxing; Chauhan, Vikash P.; Martin, John D.; Kahn, Julia; Huang, Peigen; Boucher, Yves; Fukumura, Dai; Jain, Rakesh K.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Labs, Boston, MA USA. [Incio, Joao] Hosp Sao Joao, Dept Internal Med, Oporto, Portugal. [Incio, Joao; Soares, Raquel] Univ Porto, Inst Innovat & Res Heath I3S, Metab Nutr & Endocrinol Grp, Dept Biochem,Fac Med, Oporto, Portugal. [Liu, Hao] Harvard Med Sch, Biol & Biomed Sci, Boston, MA USA. [Suboj, Priya] St Xaviers Coll, Dept Bot & Biotechnol, Trivandrum, Kerala, India. [Chen, Ivy X.] Harvard Univ, Harvard Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Babykutty, Suboj] Mar Ivanios Coll Nalanchira, Dept Zool, Trivandrum, Kerala, India. [Desphande, Vikram; Michaelson, James; Ferrone, Cristina R.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. [Michaelson, James] Massachusetts Gen Hosp, Lab Quantitat Med, Boston, MA 02114 USA. [Michaelson, James] Massachusetts Gen Hosp, Div Surg Oncol, Gillette Ctr Womens Canc, Boston, MA 02114 USA. [Michaelson, James] Harvard Med Sch, Boston, MA 02114 USA. [Michelakos, Theodoros P.; Ferrone, Cristina R.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA USA. [Michelakos, Theodoros P.; Ferrone, Cristina R.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, Boston, MA USA. RP Fukumura, D; Jain, RK (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Labs, Boston, MA USA. EM dai@steele.mgh.harvard.edu; jain@steele.mgh.harvard.edu OI Martin, John/0000-0002-9828-8203; Grahovac, Jelena/0000-0003-1430-8682 FU NIH [CA80124, CA85140, CA96915, CA115767, CA126642]; Lustgarten Foundation; Foundation for Science and Technology (Portugal, POPH/FSE funding program); Austrian Science Fund (FWF) [J3747-B28] FX This study was supported in part by the NIH (CA80124, CA85140, CA96915, CA115767, and CA126642 to R.K. Jain and D. Fukumura), the Lustgarten Foundation (research grant to R.K. Jain), the Foundation for Science and Technology (Portugal, POPH/FSE funding program, fellowship and research grant to J. Incio), and the Austrian Science Fund (FWF), project number J3747-B28 (to M. Pinter). NR 73 TC 10 Z9 10 U1 3 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD AUG PY 2016 VL 6 IS 8 BP 852 EP 869 DI 10.1158/2159-8290.CD-15-1177 PG 18 WC Oncology SC Oncology GA DW0TO UT WOS:000383355900023 PM 27246539 ER PT J AU Aguirre, AJ Meyers, RM Weir, BA Vazquez, F Zhang, CZ Ben-David, U Cook, A Ha, G Harrington, WF Doshi, MB Kost-Alimova, M Gill, S Xu, H Ali, LD Jiang, GZ Pantel, S Lee, Y Goodale, A Cherniack, AD Oh, C Kryukov, G Cowley, GS Garraway, LA Stegmaier, K Roberts, CW Golub, TR Meyerson, M Root, DE Tsherniak, A Hahn, WC AF Aguirre, Andrew J. Meyers, Robin M. Weir, Barbara A. Vazquez, Francisca Zhang, Cheng-Zhong Ben-David, Uri Cook, April Ha, Gavin Harrington, William F. Doshi, Mihir B. Kost-Alimova, Maria Gill, Stanley Xu, Han Ali, Levi D. Jiang, Guozhi Pantel, Sasha Lee, Yenarae Goodale, Amy Cherniack, Andrew D. Oh, Coyin Kryukov, Gregory Cowley, Glenn S. Garraway, Levi A. Stegmaier, Kimberly Roberts, Charles W. Golub, Todd R. Meyerson, Matthew Root, David E. Tsherniak, Aviad Hahn, William C. TI Genomic Copy Number Dictates a Gene-Independent Cell Response to CRISPR/Cas9 Targeting SO CANCER DISCOVERY LA English DT Article ID ONE-STEP GENERATION; CANCER; CRISPR-CAS9; ACTIVATION; TRANSCRIPTION; SCREENS; SYSTEM; MICE; QUANTIFICATION; REARRANGEMENTS AB The CRISPR/Cas9 system enables genome editing and somatic cell genetic screens in mammalian cells. We performed genome-scale loss-of-function screens in 33 cancer cell lines to identify genes essential for proliferation/survival and found a strong correlation between increased gene copy number and decreased cell viability after genome editing. Within regions of copy-number gain, CRISPR/Cas9 targeting of both expressed and unexpressed genes, as well as intergenic loci, led to significantly decreased cell proliferation through induction of a G(2) cell-cycle arrest. By examining single-guide RNAs that map to multiple genomic sites, we found that this cell response to CRISPR/Cas9 editing correlated strongly with the number of target loci. These observations indicate that genome targeting by CRISPR/Cas9 elicits a gene-independent antiproliferative cell response. This effect has important practical implications for the interpretation of CRISPR/Cas9 screening data and confounds the use of this technology for the identification of essential genes in amplified regions. SIGNIFICANCE: We found that the number of CRISPR/Cas9-induced DNA breaks dictates a geneindependent antiproliferative response in cells. These observations have practical implications for using CRISPR/Cas9 to interrogate cancer gene function and illustrate that cancer cells are highly sensitive to site-specific DNA damage, which may provide a path to novel therapeutic strategies. Cancer Discov; 6( 8); 914-29. (C) 2016 AACR. C1 [Aguirre, Andrew J.; Weir, Barbara A.; Vazquez, Francisca; Zhang, Cheng-Zhong; Cook, April; Ha, Gavin; Doshi, Mihir B.; Gill, Stanley; Kryukov, Gregory; Garraway, Levi A.; Stegmaier, Kimberly; Golub, Todd R.; Meyerson, Matthew; Hahn, William C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Aguirre, Andrew J.; Meyers, Robin M.; Weir, Barbara A.; Vazquez, Francisca; Zhang, Cheng-Zhong; Ben-David, Uri; Cook, April; Ha, Gavin; Harrington, William F.; Doshi, Mihir B.; Kost-Alimova, Maria; Gill, Stanley; Xu, Han; Ali, Levi D.; Jiang, Guozhi; Pantel, Sasha; Lee, Yenarae; Goodale, Amy; Cherniack, Andrew D.; Oh, Coyin; Kryukov, Gregory; Cowley, Glenn S.; Garraway, Levi A.; Stegmaier, Kimberly; Roberts, Charles W.; Golub, Todd R.; Meyerson, Matthew; Root, David E.; Tsherniak, Aviad; Hahn, William C.] Broad Inst Harvard & MIT, 415 Main St, Cambridge, MA 02142 USA. [Aguirre, Andrew J.; Garraway, Levi A.; Hahn, William C.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Aguirre, Andrew J.; Garraway, Levi A.; Stegmaier, Kimberly; Golub, Todd R.; Meyerson, Matthew; Hahn, William C.] Harvard Med Sch, Boston, MA USA. [Garraway, Levi A.; Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Stegmaier, Kimberly] Boston Childrens Hosp, Boston, MA USA. [Roberts, Charles W.] St Jude Childrens Res Hosp, Memphis, TN USA. [Meyerson, Matthew] Harvard Med Sch, Dept Pathol, Boston, MA USA. [Meyerson, Matthew; Hahn, William C.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Hahn, William C.] Dana Farber Canc Inst, Med Oncol, 450 Brookline Ave,Dana 1538, Boston, MA 02215 USA. RP Tsherniak, A (reprint author), Broad Inst Harvard & MIT, 415 Main St, Cambridge, MA 02142 USA.; Hahn, WC (reprint author), Dana Farber Canc Inst, Med Oncol, 450 Brookline Ave,Dana 1538, Boston, MA 02215 USA. EM aviad@broadinstitute.org; william_hahn@dfci.harvard.edu OI Oh, Coyin/0000-0002-5732-3471 FU Pancreatic Cancer Action Network Samuel Stroum Fellowship; Hope Funds for Cancer Postdoctoral Fellowship; American Society of Clinical Oncology Young Investigator Award; Dana-Farber Cancer Institute Hale Center for Pancreatic Cancer; Perry S. Levy Endowed Fellowship; Harvard Catalyst and Harvard Clinical and Translational Science Center [UL1 TR001102]; Slim Initiative for Genomic Medicine; Carlos Slim Foundation in Mexico; [R01 CA130988]; [U01 CA199253]; [U01 CA176058]; [P01 CA154303]; [P50 CA12700323] FX This project was supported by R01 CA130988 (W.C. Hahn), U01 CA199253 (W.C. Hahn), U01 CA176058 (W.C. Hahn), P01 CA154303 (W.C. Hahn), and P50 CA12700323 (W.C. Hahn and A.J. Aguirre). A.J. Aguirre was supported by the Pancreatic Cancer Action Network Samuel Stroum Fellowship, Hope Funds for Cancer Postdoctoral Fellowship, American Society of Clinical Oncology Young Investigator Award, Dana-Farber Cancer Institute Hale Center for Pancreatic Cancer, Perry S. Levy Endowed Fellowship, and the Harvard Catalyst and Harvard Clinical and Translational Science Center (UL1 TR001102). This work was conducted as part of the Slim Initiative for Genomic Medicine, a project funded by the Carlos Slim Foundation in Mexico. NR 48 TC 15 Z9 16 U1 3 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD AUG PY 2016 VL 6 IS 8 BP 914 EP 929 DI 10.1158/2159-8290.CD-16-0154 PG 16 WC Oncology SC Oncology GA DW0TO UT WOS:000383355900027 PM 27260156 ER PT J AU Pernar, CH Markt, SC McKay, RR Mucci, LA AF Pernar, Claire H. Markt, Sarah C. McKay, Rana R. Mucci, Lorelei A. TI CHALLENGE Trial 1 Year Feasibility Results-Letter SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Letter ID PHYSICAL-ACTIVITY; CANCER-DIAGNOSIS; SURVIVAL C1 [Pernar, Claire H.; Markt, Sarah C.; Mucci, Lorelei A.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [McKay, Rana R.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pernar, CH (reprint author), Harvard TH Chan Sch Publ Hlth, 677 Huntington Ave,Kresge 911, Boston, MA 02115 USA. EM cpernar@mail.harvard.edu FU NCI NIH HHS [T32 CA009001]; NIEHS NIH HHS [T32 ES007069] NR 5 TC 0 Z9 0 U1 0 U2 0 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 AUG PY 2016 VL 25 IS 8 BP 1277 EP 1277 DI 10.1158/1055-9965.EPI-16-0393 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA DV6JV UT WOS:000383042300012 PM 27418272 ER PT J AU Sridharan, V Gjini, E Liao, XY Chau, NG Haddad, RI Severgnini, M Hammerman, P El-Naggar, A Freeman, GJ Hodi, FS Rodig, SJ Dranoff, G Schoenfeld, JD AF Sridharan, Vishwajith Gjini, Evisa Liao, Xiaoyun Chau, Nicole G. Haddad, Robert I. Severgnini, Mariano Hammerman, Peter El-Naggar, Adel Freeman, Gordon J. Hodi, F. Stephen Rodig, Scott J. Dranoff, Glenn Schoenfeld, Jonathan D. TI Immune Profiling of Adenoid Cystic Carcinoma: PD-L2 Expression and Associations with Tumor-Infiltrating Lymphocytes SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID CELL LUNG-CANCER; METASTATIC MELANOMA; MUTATIONAL LANDSCAPE; ANTI-PD-L1 ANTIBODY; BREAST-CANCER; NECK-CANCER; BLOCKADE; IMMUNOTHERAPY; IPILIMUMAB; HEAD AB Adenoid cystic carcinoma (ACC) is among the most lethal salivary gland tumors, with no treatments for metastatic disease that prolong survival. We examined tissue from 28 primary and metastatic ACC deposits obtained from 21 patients for infiltrating immune cells and PD-L1/PD-L2 expression and determined mRNA profiles of over 1,400 oncogenic and immune-related genes. We also assessed the effect of chemoradiation on immune mediators in a patient who had serial biopsies available. Most tumors expressed PD-L2 but had few infiltrating immune cells. Lack of immune-cell infiltrate was associated with expression of genes in the beta-catenin/Wnt and PI3K pathways. Additionally, certain transcripts linked to growth and invasion were differentially expressed among primary and metastatic deposits. Chemoradiation appeared to increase CD8(+) effector T cells, decrease regulatory T cells, and promote a systemic humoral response. These data suggest a potential role for PD-L2 inhibition and immune modulation as treatment for patients with ACC. (C) 2016 AACR. C1 [Sridharan, Vishwajith; Schoenfeld, Jonathan D.] Brigham & Womens Hosp, Dana Farber Canc Ctr, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. [Sridharan, Vishwajith] Harvard Med Sch, Harvard MIT Div Hlth Sci & Technol, Boston, MA USA. [Gjini, Evisa; Liao, Xiaoyun] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Severgnini, Mariano; Hodi, F. Stephen] Brigham & Womens Hosp, Dana Farber Canc Ctr, Ctr Immunooncol, 75 Francis St, Boston, MA 02115 USA. [Chau, Nicole G.; Haddad, Robert I.; Hammerman, Peter; Freeman, Gordon J.; Hodi, F. Stephen] Brigham & Womens Hosp, Dana Farber Canc Ctr, Dept Med Oncol, 75 Francis St, Boston, MA 02115 USA. [El-Naggar, Adel] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Dana Farber Canc Ctr, 75 Francis St, Boston, MA 02115 USA. [Dranoff, Glenn] Novartis Inst Biomed Res, Cambridge, MA USA. RP Schoenfeld, JD (reprint author), Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, 450 Brookline Ave,DA L2-57, Boston, MA 02114 USA. EM jdschoenfeld@partners.org FU NCI NIH HHS [P30 CA016672] NR 56 TC 0 Z9 0 U1 0 U2 0 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 AUG PY 2016 VL 4 IS 8 BP 679 EP 687 DI 10.1158/2326-6066.CIR-16-0031 PG 9 WC Oncology; Immunology SC Oncology; Immunology GA DV6NE UT WOS:000383052800006 PM 27312343 ER PT J AU Song, MY Konijeti, GG Yuan, C Ananthakrishnan, AN Ogino, S Fuchs, CS Giovannucci, EL Ng, K Chan, AT AF Song, Mingyang Konijeti, Gauree Gupta Yuan, Chen Ananthakrishnan, Ashwin N. Ogino, Shuji Fuchs, Charles S. Giovannucci, Edward L. Ng, Kimmie Chan, Andrew T. TI Plasma 25-Hydroxyvitamin D, Vitamin D Binding Protein, and Risk of Colorectal Cancer in the Nurses' Health Study SO CANCER PREVENTION RESEARCH LA English DT Article ID GROUP-SPECIFIC COMPONENT; MACROPHAGE ACTIVATING FACTOR; C5A DES ARG; GC-GLOBULIN; INFLAMMATORY MARKERS; CONTROLLED-TRIAL; SCREENING TRIAL; SERUM; CALCIUM; MORTALITY AB Total circulating 25-hydroxyvitamin D [25(OH) D)] has been associated with lower risk of colorectal cancer. The physiologic mechanism, however, may be more directly related to the free or bioavailable fraction of 25(OH) D, which is influenced by levels of vitaminD binding protein (VDBP). We assessed the association of prediagnosis total, free, and bioavailable 25(OH) D and VDBP with colorectal cancer risk among predominantly white women in the Nurses' Health Study (NHS) who provided a blood specimen in 1989-1990. We documented 378 cases of colorectal cancer through 2011 and matched them to 689 controls according to age and time of blood draw. We genotyped two common polymorphisms in the gene coding VDBP and calculated free and bioavailable 25(OH) D levels based on total 25(OH) D, VDBP, albumin, and their estimated genotype-specific binding affinities. Total 25(OH) D was associated with lower colorectal cancer risk (P for trend = 0.01). Compared with women in the lowest quintile of total 25 (OH) D, those in the highest quintile had a multivariable-adjusted odds ratio (OR) for colorectal cancer of 0.54 [95% confidence interval (CI), 0.33-0.87]. Comparing extreme quintiles, we did not find any significant association with risk of colorectal cancer for VDBP (OR, 0.98; 95% CI, 0.65-1.47), free 25(OH) D (OR, 0.71; 95% CI, 0.46-1.10), or bioavailable 25(OH) D (OR, 0.92; 95% CI, 0.60-1.42). In conclusion, prediagnosis levels of total, but not free or bioavailable 25(OH) D, were associated with lower colorectal cancer risk. Although our findings support an inverse association of vitamin D with colorectal cancer, this association does not appear to be due to the unbound or bioavailable fraction of circulating vitamin D. (C) 2016 AACR. C1 [Song, Mingyang; Chan, Andrew T.] Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA 02114 USA. [Song, Mingyang; Ananthakrishnan, Ashwin N.; Ogino, Shuji; Fuchs, Charles S.; Giovannucci, Edward L.; Ng, Kimmie; Chan, Andrew T.] Harvard Med Sch, Boston, MA USA. [Song, Mingyang; Ananthakrishnan, Ashwin N.; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Song, Mingyang; Yuan, Chen; Giovannucci, Edward L.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Konijeti, Gauree Gupta] Scripps Clin, Div Gastroenterol, La Jolla, CA 92037 USA. [Konijeti, Gauree Gupta] Scripps Translat Sci Inst, La Jolla, CA USA. [Ogino, Shuji; Fuchs, Charles S.; Ng, Kimmie] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Div MPE Mol Pathol Epidemiol, 75 Francis St, Boston, MA 02115 USA. [Ogino, Shuji; Giovannucci, Edward L.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Fuchs, Charles S.; Giovannucci, Edward L.; Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Chan, Andrew T.] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA USA. RP Chan, AT (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, 55 Fruit St,GRJ 825C, Boston, MA 02114 USA. EM achan@mgh.harvard.edu FU NIH [UM1 CA186107, P01 CA87969, R01 CA49449, R01 CA137178, R01 CA151993, R35 CA197735, K07 CA148894, K24 DK098311, P50 CA127003]; NIH/NCATS [KL2 TR001112]; American Society of Clinical Oncology/Conquer Cancer Foundation FX This work was supported by the NIH (UM1 CA186107 to M.J. Stampfer, P01 CA87969 to M.J. Stampfer, R01 CA49449 to S.E. Hankinson, R01 CA137178 to A.T. Chan, R01 CA151993 to S. Ogino, R35 CA197735 to S. Ogino, K07 CA148894 to K. Ng, K24 DK098311 to A.T. Chan, and P50 CA127003 to C.S. Fuchs and NIH/NCATS Grant Number KL2 TR001112 to G.G. Konijeti) and the American Society of Clinical Oncology/Conquer Cancer Foundation (to C.S. Fuchs). NR 52 TC 2 Z9 2 U1 3 U2 3 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 AUG PY 2016 VL 9 IS 8 BP 664 EP 672 DI 10.1158/1940-6207.CAPR-16-0053 PG 9 WC Oncology SC Oncology GA DV7AZ UT WOS:000383089500006 PM 27246684 ER PT J AU Peloso, GM Lange, LA Varga, TV Nickerson, DA Smith, JD Griswold, ME Musani, S Polfus, LM Mei, H Gabriel, S Quarells, RC Altshuler, D Boerwinkle, E Daly, MJ Neale, B Correa, A Reiner, AP Wilson, JG Kathiresan, S AF Peloso, Gina M. Lange, Leslie A. Varga, Tibor V. Nickerson, Deborah A. Smith, Joshua D. Griswold, Michael E. Musani, Solomon Polfus, Linda M. Mei, Hao Gabriel, Stacey Quarells, Rakale Collins Altshuler, David Boerwinkle, Eric Daly, Mark J. Neale, Benjamin Correa, Adolfo Reiner, Alex P. Wilson, James G. Kathiresan, Sekar TI Association of Exome Sequences With Cardiovascular Traits Among Blacks in the Jackson Heart Study SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE alleles; exome; lipids; missense; mutation ID OF-FUNCTION MUTATIONS; GENOME-WIDE ASSOCIATION; BLOOD-LIPIDS; PCSK9; VARIANTS; DISEASE; CHOLESTEROL; POPULATION; APOC3; RISK AB Background-The correlation of null alleles with human phenotypes can provide insight into gene function in humans. In individuals of African ancestry, we set out to identify null and damaging missense variants, and test these variants for association with a range of cardiovascular phenotypes. Methods and Results-We performed whole-exome sequencing in 3223 black individuals from the Jackson Heart Study and found a total of 729 666 variant sites with minor allele frequency <5%, including 17 263 null variants and 49 929 missense variants predicted to be damaging by in silico algorithms. We tested null and damaging missense variants within each gene for association with 36 cardiovascular traits. We found 3 associations that met our prespecified level of significance (alpha=1.1x10(-7)). Null and damaging missense variants in PCSK9 were associated with 36 mg/dL lower low-density lipoprotein cholesterol (P=3x10-21). Three individuals in their 50s with complete PCSK9 deficiency (each compound heterozygote for PCSK9 p. Y142X and p. C679X) were identified, with one having a coronary artery calcification score in the 83rd percentile despite a low-density lipoprotein cholesterol of 32 mg/dL. A damaging missense variant in HBQ1 (p. G52A) was associated with a 2 pg/cell lower mean corpuscular hemoglobin (P=9x10(-13)) and rare damaging missense variants in VPS13A with higher red blood cell distribution width (P=9.9x10(-8)). Conclusions-A limited number of null/damaging alleles with a large effect on cardiovascular traits were detectable in approximate to 3000 black individuals. C1 [Peloso, Gina M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Peloso, Gina M.; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 5-248, Boston, MA 02114 USA. [Daly, Mark J.; Neale, Benjamin] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Peloso, Gina M.; Gabriel, Stacey; Altshuler, David; Daly, Mark J.; Neale, Benjamin; Kathiresan, Sekar] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Lange, Leslie A.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Varga, Tibor V.] Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden. [Nickerson, Deborah A.; Smith, Joshua D.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Griswold, Michael E.; Mei, Hao] Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, Jackson, MS 39216 USA. [Musani, Solomon] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. [Correa, Adolfo] Univ Mississippi, Med Ctr, Dept Pediat & Med, Jackson, MS 39216 USA. [Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA. [Polfus, Linda M.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Quarells, Rakale Collins] Morehouse Sch Med, Cardiovasc Res Inst, Atlanta, GA 30310 USA. [Altshuler, David; Kathiresan, Sekar] Harvard Med Sch, Dept Med, Boston, MA USA. [Reiner, Alex P.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 5-248, Boston, MA 02114 USA.; Peloso, GM (reprint author), Boston Univ, Dept Biostat, 801 Massachusetts Ave,3rd Floor, Boston, MA 02118 USA. EM gpeloso@bu.edu; skathiresan@partners.org FU National Heart, Lung, and Blood Institute of the National Institutes of Health [K01HL125751]; Research Scholar award from the Massachusetts General Hospital (MGH); Howard Goodman Fellowship from MGH; Donovan Family Foundation [R01HL107816]; Fondation Leducq; National Heart, Lung, and Blood Institute [HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN2682013 00049C, HHSN268201300050C]; National Institute on Minority Health and Health Disparities; National Institute on Minority Health and Health Disparities [1RC4MD005964] FX G.M.P. is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number K01HL125751. S.K. is supported by a Research Scholar award from the Massachusetts General Hospital (MGH), the Howard Goodman Fellowship from MGH, the Donovan Family Foundation, R01HL107816, and a grant from Fondation Leducq. The Jackson Heart Study is supported by contracts HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN2682013 00049C, and HHSN268201300050C from the National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities. The MH-GRID Network (Investigators: Rakale C. Quarells, Gary H. Gibbons, Donna K. Arnett, Robert L. Davis, Suzanne M. Leal, Deborah A. Nickerson, James Perkins, Charles N. Rotimi, Joel H. Saltz, Herman A. Taylor, and James G. Wilson) was supported, in part, by a grant from the National Institute on Minority Health and Health Disparities (grant # 1RC4MD005964). NR 36 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1942-325X EI 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD AUG PY 2016 VL 9 IS 4 BP 368 EP 374 DI 10.1161/CIRCGENETICS.116.001410 PG 7 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA DU5EC UT WOS:000382234000008 PM 27422940 ER PT J AU Baggish, AL AF Baggish, Aaron L. TI Exercise-Induced Cardiac Remodeling Competitive Athletes Are Just the Tip of the Iceberg SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE Editorials; athlete; blood pressure; cross-sectional studies; exercise; habit ID MAGNETIC-RESONANCE; ENDURANCE; HEART; MASS C1 [Baggish, Aaron L.] Massachusetts Gen Hosp, Cardiovasc Performance Program, Yawkey Suite 5B,55 Fruit St, Boston, MA 02114 USA. RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Cardiovasc Performance Program, Yawkey Suite 5B,55 Fruit St, Boston, MA 02114 USA. EM abaggish@partners.org NR 19 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD AUG PY 2016 VL 9 IS 8 AR e005321 DI 10.1161/CIRCIMAGING.116.005321 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA DU5FF UT WOS:000382236900016 ER PT J AU Ferencik, M AF Ferencik, Maros TI Insights Into Coronary Plaque Microstructure Differences Between Women and Men SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE Editorials; acute coronary syndrome; atherosclerosis; coronary artery disease; optical coherence tomography; women's health; smoking ID OPTICAL COHERENCE TOMOGRAPHY; ROMICAT-II TRIAL; ACUTE CHEST-PAIN; SEX-DIFFERENCES; RISK; ATHEROSCLEROSIS; ANGIOGRAPHY; OUTCOMES; EVENTS; BURDEN C1 [Ferencik, Maros] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, 3180 Sam Jackson Pk Rd,Mail Code UHN62, Portland, OR 97239 USA. [Ferencik, Maros] Harvard Med Sch, Dept Radiol, Boston, MA USA. [Ferencik, Maros] Harvard Med Sch, Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA USA. RP Ferencik, M (reprint author), Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, 3180 Sam Jackson Pk Rd,Mail Code UHN62, Portland, OR 97239 USA. EM ferencik@ohsu.edu NR 20 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD AUG PY 2016 VL 9 IS 8 AR e005343 DI 10.1161/CIRCIMAGING.116.005343 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA DU5FF UT WOS:000382236900021 ER PT J AU ter Maaten, JM Damman, K Hanberg, JS Givertz, MM Metra, M O'Connor, CM Teerlink, JR Ponikowski, P Cotter, G Davison, B Cleland, JG Bloomfield, DM Hillege, HL van Veldhuisen, DJ Voors, AA Testani, JM AF ter Maaten, Jozine M. Damman, Kevin Hanberg, Jennifer S. Givertz, Michael M. Metra, Marco O'Connor, Christopher M. Teerlink, John R. Ponikowski, Piotr Cotter, Gad Davison, Beth Cleland, John G. Bloomfield, Daniel M. Hillege, Hans L. van Veldhuisen, Dirk J. Voors, Adriaan A. Testani, Jeffrey M. TI Hypochloremia, Diuretic Resistance, and Outcome in Patients With Acute Heart Failure SO CIRCULATION-HEART FAILURE LA English DT Article DE blood urea nitrogen; chlorides; creatinine; diuretics; electrolytes ID SENSING MECHANISM; EUROPEAN-SOCIETY; TASK-FORCE; CHLORIDE; ASSOCIATION; ROLOFYLLINE; GUIDELINES; MANAGEMENT; ANTAGONIST; CARDIOLOGY AB Background-Chloride plays a role in renal salt sensing, neurohormonal activation, and regulation of diuretic targets, and hypochloremia predicts mortality in acute heart failure (AHF). AHF therapies, such as diuretics, alter chloride homeostasis. We studied the association between (changes in) chloride levels and diuretic responsiveness, decongestion, and mortality in patients with AHF. Methods and Results-Patients hospitalized for AHF in the PROTECT trial (n=2033) with serum chloride levels within 24 hours of admission and 14 days later were studied (n=1960). Hypochloremia was defined as serum chloride <96 mEq/L. Mean baseline chloride was 100.8+/-5.0 mEq/L. Low baseline chloride was associated with high bicarbonate, poor diuretic response, less hemoconcentration, and worsening heart failure (all P<0.01). Newly developed hypochloremia at day 14 was common and associated with a decline in renal function and an increase in blood urea nitrogen (P<0.01). In multivariable analyses, chloride measured at day 14, but not baseline chloride, was strongly and independently associated with mortality through 180 days (hazard ratio per unit decrease: 1.07 [1.03-1.10]; P<0.001). In comparison, sodium was not significantly associated with mortality after multivariable adjustment at any time point. Hypochloremia at baseline that resolved was not associated with mortality (P=0.55), but new or persistent hypochloremia at day 14 was associated with increased mortality (hazard ratio: 3.11 [2.17-4.46]; P<0.001). Conclusions-Low serum chloride at AHF hospital admission was strongly associated with impaired decongestion. New or persistent hypochloremia 14 days later was independently associated with reduced survival, whereas hypochloremia that resolved by day 14 was not. C1 [ter Maaten, Jozine M.; Damman, Kevin; Hillege, Hans L.; van Veldhuisen, Dirk J.; Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, NL-9700 AB Groningen, Netherlands. [ter Maaten, Jozine M.; Hanberg, Jennifer S.; Testani, Jeffrey M.] Yale Univ, Sch Med, Program Appl Translat Res, New Haven, CT USA. [Givertz, Michael M.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Metra, Marco] Univ Brescia, I-25121 Brescia, Italy. [O'Connor, Christopher M.] Inova Heart & Vasc Inst, Falls Church, VA USA. [Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. [Ponikowski, Piotr] Med Univ, Clin Mil Hosp, Wroclaw, Poland. [Cotter, Gad; Davison, Beth] Momentum Res, Durham, NC USA. [Cleland, John G.] Univ Hull, Kingston Upon Hull, Yorks, England. [Bloomfield, Daniel M.] Merck Res Labs, Rahway, NJ USA. [Testani, Jeffrey M.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. RP Voors, AA (reprint author), Univ Med Ctr Groningen, Hanzepl 1, NL-9713 GZ Groningen, Netherlands. EM a.a.voors@umcg.nl RI Ponikowski, Piotr/O-6454-2015 OI Ponikowski, Piotr/0000-0002-3391-7064 FU NovoCardia, a subsidiary of Merck FX The PROTECT trial was supported by NovoCardia, a subsidiary of Merck. NR 20 TC 2 Z9 2 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD AUG PY 2016 VL 9 IS 8 AR UNSP e003109 DI 10.1161/CIRCHEARTFAILURE.116.003109 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DU5EQ UT WOS:000382235400009 ER PT J AU Kanwal, F Kramer, JR El-Serag, HB Frayne, S Clark, J Cao, YM Taylor, T Smith, D White, D Asch, SM AF Kanwal, Fasiha Kramer, Jennifer R. El-Serag, Hashem B. Frayne, Susan Clark, Jack Cao, Yumei Taylor, Thomas Smith, Donna White, Donna Asch, Steven M. TI Race and Gender Differences in the Use of Direct Acting Antiviral Agents for Hepatitis C Virus SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE Veterans; healthcare disparities; access; quality; hepatitis ID GENOTYPE 1 INFECTION; RACIAL-DIFFERENCES; VETERANS-AFFAIRS; HCV; ABT-450/R-OMBITASVIR; LEDIPASVIR; SOFOSBUVIR; DASABUVIR; RIBAVIRIN; CIRRHOSIS AB Background. Direct acting antiviral agents (DAA) are highly effective yet expensive. Disparities by race and/or gender often exist in the use of costly medical advances as they become available. Methods. We examined a cohort of hepatitis C virus (HCV) patients who received care at the Veterans Administration facilities nationwide. We evaluated the effect of race and gender on DAA receipt after adjusting for socioeconomic status, liver disease severity, comorbidity, and propensity for healthcare use. To determine if disparities had changed over time, we conducted a similar analysis of HCV patients who were seen in the previous standard of care treatment era. Results. Of the 145 596 patients seen in the current DAA era, 17 791 (10.2%) received treatment during the first 16 months of DAA approval. Black patients had 21% lower odds of receiving DAA than whites (odds ratio [OR] = 0.79; 95% confidence interval [CI],.75,.84). Overall, women were as likely to receive treatment as men (OR = 0.99; 95% CI,.90-1.09). However, the odds of receiving DAAs were 29% lower for younger women compared with younger men (OR = 0.71, 95% CI, .54-.93). Similar to the DAA cohort, black patients had significantly lower odds of receiving treatment than whites (OR = 0.74, 95% CI, .69-.79) in the previous treatment era. The racial difference between the 2 eras did not reach statistical significance. Conclusions. There were unexplained differences among HCV population subgroups in the receipt of new DAA treatment. Targeted interventions are needed for black patients and younger women. C1 [Kanwal, Fasiha; Kramer, Jennifer R.; El-Serag, Hashem B.; Cao, Yumei; Smith, Donna; White, Donna] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Ctr Innovat Qual Effectiveness & Safety IQuESt, Houston, TX 77030 USA. [Kanwal, Fasiha; El-Serag, Hashem B.] Baylor Coll Med, Sect Gastroenterol & Hepatol, Houston, TX 77030 USA. [Kanwal, Fasiha; Kramer, Jennifer R.; El-Serag, Hashem B.; White, Donna] Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Kanwal, Fasiha; El-Serag, Hashem B.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Frayne, Susan; Taylor, Thomas; Asch, Steven M.] VA Palo Alto Healthcare Syst, Fostering High Value Care, Ctr Innovat Implementat Ci2i, Stanford, CA USA. [Clark, Jack] Edith Nourse Rogers Mem Vet Hosp, Ctr Healthcare Org & Implementat, Boston, MA USA. [Clark, Jack] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02215 USA. RP Kanwal, F (reprint author), Michael E DeBakey VA, Ctr Innovat Qual Effectiveness & Safety IQuESt, 2002 Holcombe Blvd,Ste 152, Houston, TX 77030 USA.; Kanwal, F (reprint author), Baylor Coll Med, 2002 Holcombe Blvd,Ste 152, Houston, TX 77030 USA. EM kanwal@bcm.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development Service [VA IIR 13-059] FX The research was supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development Service (VA IIR 13-059). F.K. is a physician research scientist at the Center for Innovations in Quality, Effectiveness, and Safety (#CIN 13-413), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas. NR 31 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 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG 1 PY 2016 VL 63 IS 3 BP 291 EP 299 DI 10.1093/cid/ciw249 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DV8QP UT WOS:000383201900001 PM 27131869 ER PT J AU Turbett, SE Mansour, MK AF Turbett, Sarah E. Mansour, Michael K. TI Fecal ESBL Screening: Are We Ready for This Information? SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material DE ESBL; infection control; fecal colonization; Enterobacteriaceae; screening ID RESISTANT STAPHYLOCOCCUS-AUREUS; ESCHERICHIA-COLI; INTENSIVE-CARE; INFECTION; COLONIZATION; RISK; ENTEROBACTERIACEAE; CARRIAGE; DECOLONIZATION C1 [Turbett, Sarah E.; Mansour, Michael K.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Turbett, Sarah E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Mansour, MK (reprint author), Massachusetts Gen Hosp, Jackson Bldg 1328A,55 Fruit St, Boston, MA 02114 USA. EM mkmansour@mgh.harvard.edu FU NIAID NIH HHS [K08 AI110655] NR 20 TC 0 Z9 0 U1 2 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG 1 PY 2016 VL 63 IS 3 BP 319 EP 321 DI 10.1093/cid/ciw288 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DV8QP UT WOS:000383201900004 PM 27143673 ER PT J AU Tasdemir-Yilmaz, OE Segal, RA AF Tasdemir-Yilmaz, Ozge E. Segal, Rosalind A. TI There and back again: coordinated transcription, translation and transport in axonal survival and regeneration SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID MESSENGER-RNA LOCALIZATION; BETA-ACTIN SYNTHESIS; BINDING-PROTEIN 1; NERVOUS-SYSTEM; NEURONAL SURVIVAL; PERIPHERAL-NERVE; GROWTH; INJURY; COMPLEX; SIGNAL AB Neurons are highly polarized cells with axonal and dendritic projections that extend over long distances. Target-derived neurotrophins provide local axonal cues that function in developing neurons, while physical or chemical injuries to long axons initiate local environmental cues in mature neurons. In both instances initial responses at the location of stimulation or injury must be coordinated with changes in the transcriptional program and subsequent changes in axonal protein content. To achieve this coordination, intracellular signals move 'there and back again' between axons and the nucleus. Here, we review new findings on neuronal responses to growth factors and injury and highlight the coordination of transcription, translation and transport required to mediate communication between axons and cell bodies. C1 [Tasdemir-Yilmaz, Ozge E.; Segal, Rosalind A.] Harvard Med Sch, Dept Neurobiol, Boston, MA 02115 USA. [Tasdemir-Yilmaz, Ozge E.; Segal, Rosalind A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. RP Segal, RA (reprint author), Harvard Med Sch, Dept Neurobiol, Boston, MA 02115 USA.; Segal, RA (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. EM Rosalind_segal@dfci.harvard.edu FU National Institutes of Health [RO1 NS050674, T32 AG000222] FX We would like to apologize to authors whose studies were not included in this review due to space constraints. We would like to thank Katherina Cosker, Sarah Pease, Xuesong Zhao, Maria Pazyra-Murphy and Emily Chadwick for helpful comments and editing. Our research is supported by the National Institutes of Health grant RO1 NS050674 (RAS) and T32 AG000222 (OETY). NR 47 TC 2 Z9 2 U1 3 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 EI 1873-6882 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD AUG PY 2016 VL 39 BP 62 EP 68 DI 10.1016/j.conb.2016.04.006 PG 7 WC Neurosciences SC Neurosciences & Neurology GA DU6VI UT WOS:000382352300010 PM 27131422 ER PT J AU O'Neill, AC Shinagare, AB Kurra, V Tirumani, SH Jagannathan, JP Baheti, AD Hornick, JL George, S Ramaiya, NH AF O'Neill, A. C. Shinagare, A. B. Kurra, V. Tirumani, S. H. Jagannathan, J. P. Baheti, A. D. Hornick, J. L. George, S. Ramaiya, N. H. TI Assessment of metastatic risk of gastric GIST based on treatment-naive CT features SO EJSO LA English DT Article DE Gastrointestinal stromal tumor; Stomach; CT; Risk stratification; Metastasis ID GASTROINTESTINAL STROMAL TUMORS; TERM-FOLLOW-UP; COMPUTED-TOMOGRAPHY; CONSENSUS APPROACH; DIAGNOSIS; PATHOLOGY; PROGNOSIS; SURVIVAL; STOMACH AB Objective: To study whether the CT features of treatment-naive gastric GIST may be used to assess metastatic risk. Methods: In this MB approved retrospective study, with informed consent waived, contrast enhanced CT images of 143 patients with pathologically confirmed treatment-naive gastric GIST (74 men, 69 women; mean age 61 years, SD +/- 14) were reviewed in consensus by two oncoradiologists blinded to clinicopathologic features and clinical outcome and morphologic features were recorded. The metastatic spread was recorded using available imaging studies and electronic medical records (median follow up 40 months, interquartile range, IQR, 21-61). The association of maximum size in any plane (<= 10 cm or >10 cm), outline (smooth or irregular/lobulated), cystic areas (<= 50% or >50%), exophytic component (<= 50% or >50%), and enhancing solid component (present or absent) with metastatic disease were analyzed using univariate (Fisher's exact test) and multivariate (logistic regression) analysis. Results: Metastatic disease developed in 42 (29%) patients (28 at presentation, 14 during follow-up); 23 (16%) patients died. On multivariate analysis, tumor size >10 cm (p = 0.0001, OR 9.9), irregular/lobulated outline (p = 0.001, OR 5.6) and presence of a enhancing solid component (p < 0.0001, OR 9.1) were independent predictors of metastatic disease. On subgroup analysis, an irregular/lobulated outline and an enhancing solid component were more frequently associated with metastases in tumors <= 5 cm and >5-<= 10 cm (p < 0.05). Conclusion: CT morphologic features can be used to assess the metastatic risk of treatment-naive gastric GIST. Risk assessment based on pretreatment CT is especially useful for patients receiving neoadjuvant tyrosine kinase inhibitors and those with tumors <5 cm in size. (C) 2016 Elsevier Ltd. All rights reserved. C1 [O'Neill, A. C.; Shinagare, A. B.; Kurra, V.; Tirumani, S. H.; Jagannathan, J. P.; Baheti, A. D.; Ramaiya, N. H.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Hornick, J. L.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [George, S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Shinagare, AB (reprint author), Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. EM ashinagare@partners.org FU Bayer; Novartis; Pfizer; ARIAD; RSNA Research Scholar Grant [RSCH1422] FX Suzanne George has consulting and research funding from Bayer, Novartis, Pfizer and ARIAD.; This research project was not funded; however, Atul Shinagare is now supported by RSNA Research Scholar Grant, #RSCH1422. The grant support began after this research project was completed, but before submission of the manuscript to EJSO. NR 23 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0748-7983 EI 1532-2157 J9 EJSO-EUR J SURG ONC JI EJSO PD AUG PY 2016 VL 42 IS 8 BP 1222 EP 1228 DI 10.1016/j.ejso.2016.03.032 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA DV5XW UT WOS:000383005000018 PM 27178777 ER PT J AU DeVore, AD Hellkamp, AS Becker, RC Berkowitz, SD Breithardt, G Hacke, W Halperin, JL Hankey, GJ Mahaffey, KW Nessel, CC Singer, DE Fox, KAA Patel, MR Piccini, JP AF DeVore, Adam D. Hellkamp, Anne S. Becker, Richard C. Berkowitz, Scott D. Breithardt, Guenter Hacke, Werner Halperin, Jonathan L. Hankey, Graeme J. Mahaffey, Kenneth W. Nessel, Christopher C. Singer, Daniel E. Fox, Keith A. A. Patel, Manesh R. Piccini, Jonathan P. CA ROCKET AF Steering Comm TI Hospitalizations in patients with atrial fibrillation: an analysis from ROCKET AF SO EUROPACE LA English DT Article DE Hospitalization; Atrial fibrillation; Outcomes; Stroke; Rivaroxaban ID HEART-FAILURE; UNITED-STATES; TRIAL; RATES; PREVALENCE; MANAGEMENT; STANDARD; OUTCOMES; SAFETY; TRENDS AB The high costs associated with treatment for atrial fibrillation (AF) are primarily due to hospital care, but there are limited data to understand the reasons for and predictors of hospitalization in patients with AF. The ROCKET AF trial compared rivaroxaban with warfarin for stroke prophylaxis in AF. We described the frequency of and reasons for hospitalization during study follow-up and utilized Cox proportional hazards models to assess for baseline characteristics associated with all-cause hospitalization. Of 14 171 patients, 14% were hospitalized at least once. Of 2614 total hospitalizations, 41% were cardiovascular including 4% for AF; of the remaining, 12% were for bleeding. Compared with patients not hospitalized, hospitalized patients were older (74 vs. 72 years), and more frequently had diabetes (46 vs. 39%), prior MI (23 vs. 16%), and paroxysmal AF (19 vs. 17%), but less frequently had prior transient ischaemic attack/stroke (49 vs. 56%). After multivariable adjustment, lung disease [hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.29-1.66], diabetes [1.22, (1.11-1.34)], prior MI [1.27, (1.13-1.42)], and renal dysfunction [HR 1.07 per 5 unit GFR < 65 mL/min, (1.04-1.10)] were associated with increased hospitalization risk. Treatment assignment was not associated with differential rates of hospitalization. Nearly 1 in 7 of the moderate-to-high-risk patients with AF enrolled in this trial was hospitalized within 2 years, and both AF and bleeding were rare causes of hospitalization. Further research is needed to determine whether care pathways directed at comorbid conditions among AF patients could reduce the need for and costs associated with hospitalization. C1 [DeVore, Adam D.; Hellkamp, Anne S.; Patel, Manesh R.; Piccini, Jonathan P.] Duke Clin Res Inst, Durham, NC 27705 USA. [DeVore, Adam D.; Patel, Manesh R.; Piccini, Jonathan P.] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA. [Becker, Richard C.] Univ Cincinnati, Cincinnati, OH USA. [Berkowitz, Scott D.] Bayer HealthCare Pharmaceut, Whippany, NJ USA. [Breithardt, Guenter] Hosp Univ Munster, Munster, Germany. [Hacke, Werner] Heidelberg Univ, Heidelberg, Germany. [Halperin, Jonathan L.] Mt Sinai Sch Med, New York, NY USA. [Hankey, Graeme J.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA, Australia. [Mahaffey, Kenneth W.] Stanford Univ, Stanford, CA 94305 USA. [Nessel, Christopher C.] Janssen Res & Dev, Raritan, NJ USA. [Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fox, Keith A. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Fox, Keith A. A.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland. RP DeVore, AD (reprint author), Duke Clin Res Inst, Durham, NC 27705 USA.; DeVore, AD (reprint author), Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA. EM adam.devore@duke.edu RI Hankey, Graeme /H-4968-2014; OI Hankey, Graeme /0000-0002-6044-7328; DeVore, Adam/0000-0002-4679-2221 FU Janssen Research & Development LLC, Raritan, NJ; Bayer HealthCare AG, Leverkusen, Germany; Janssen Research and Development FX This work was supported by the Janssen Research & Development LLC, Raritan, NJ and Bayer HealthCare AG, Leverkusen, Germany. Funding to pay the Open Access publication charges for this article was provided by Janssen Research and Development. NR 18 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1099-5129 EI 1532-2092 J9 EUROPACE JI Europace PD AUG PY 2016 VL 18 IS 8 BP 1135 EP 1142 DI 10.1093/europace/euv404 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DV8TD UT WOS:000383208700005 PM 27174904 ER PT J AU Wakili, R Siebermair, J Fichtner, S Sinner, MF Klocker, E Olesch, L Hilberath, JN Sarai, S Clauss, S Sattler, S Kaab, S Estner, HL AF Wakili, Reza Siebermair, Johannes Fichtner, Stephanie Sinner, Moritz F. Klocker, Eva Olesch, Lucia Hilberath, Jan N. Sarai, Samira Clauss, Sebastian Sattler, Stefan Kaeaeb, Stefan Estner, Heidi L. TI One-year clinical outcome after ablation with a novel multipolar irrigated ablation catheter for treatment of atrial fibrillation: potential implications for clinical use SO EUROPACE LA English DT Article DE Arrhythmia; Atrial fibrillation; Ablation; Pulmonary vein isolation; nMARQ catheter ID PULMONARY VEIN ISOLATION; CIRCULAR MAPPING CATHETER; RADIOFREQUENCY ABLATION; NMARQ ABLATION; MANAGEMENT; EFFICACY AB Pulmonary vein isolation (PVI) is an established therapy for atrial fibrillation (AF). However, PVI remains a time-consuming procedure. A novel multipolar irrigated radiofrequency (RF) ablation catheter (nMARQ (TM)) is aiming to improve PVI. We investigated the influence on procedural parameters and assessed clinical outcomes after PVI using this novel catheter. Fifty-eight consecutive patients with paroxysmal AF were equally allocated (n = 29/group) to PVI treatment with (i) the novel multipolar ablation catheter (nMARQ (TM)) and (ii) a standard single-tip ablation catheter (SAC). Study endpoints included procedure time, fluoroscopy time, radiation dose, RF time, number of energy applications, and clinical outcome defined as freedom from AF after a single procedure. Successful PVI was confirmed by a separate circular, multipolar mapping catheter in all patients treated with the nMARQ (TM). Pulmonary vein isolation was achieved in 100% in the SAC group. In the nMARQ (TM) group, PVI was suggested in all patients. However, confirmatory mapping revealed persistent pulmonary vein (PV) conduction in 19 out of 29 nMARQ (TM) patients. These patients underwent further ablation, which still failed to achieve PVI in 5 of the 29 nMARQ (TM) patients, mainly due to significant temperature rise in the oesophagus and device-related limitations reaching the right inferior PV. Mean fluoroscopy time (31 +/- 12 vs. 23 +/- 10 min, P < 0.05) and (132 +/- 37 vs. 109 +/- 30 min, P < 0.05) were longer in nMARQ (TM) vs. SAC patients. Radiofrequency time was shorter in nMARQ (TM) vs. SAC group (21 +/- 9 vs. 35 +/- 12 min, P < 0.001). Radiation dose and the number of energy applications did not differ between both groups. Clinical outcome analysis revealed no significant differences (nMARQ (TM): 72 vs. SAC: 72%) after a mean follow-up of 373 +/- 278 days. The use of the nMARQ (TM) catheter is associated with important device-related limitations to achieve successful PVI. However, clinical outcomes were equivalent in nMARQ (TM)- and SAC-treated patients. C1 [Wakili, Reza; Siebermair, Johannes; Fichtner, Stephanie; Sinner, Moritz F.; Klocker, Eva; Olesch, Lucia; Sarai, Samira; Clauss, Sebastian; Sattler, Stefan; Kaeaeb, Stefan; Estner, Heidi L.] Univ Munich, Univ Hosp Munich, Dept Med 1, Munich, Germany. [Wakili, Reza; Kaeaeb, Stefan] Partner Site Munich Heart Alliance, German Cardiovasc Res Ctr DZHK, Munich, Germany. [Hilberath, Jan N.] Univ Tubingen, Dept Anesthesiol & Crit Care Med, Tubingen, Germany. [Clauss, Sebastian] Harvard Med Sch, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Wakili, R (reprint author), Univ Munich, Univ Hosp Munich, Dept Med 1, Munich, Germany.; Wakili, R (reprint author), Partner Site Munich Heart Alliance, German Cardiovasc Res Ctr DZHK, Munich, Germany. EM reza.wakili@med.uni-muenchen.de FU German Center for Cardiovascular Research (DZHK) FX The study was funded by the German Center for Cardiovascular Research (DZHK). NR 14 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1099-5129 EI 1532-2092 J9 EUROPACE JI Europace PD AUG PY 2016 VL 18 IS 8 BP 1170 EP 1178 DI 10.1093/europace/euv349 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DV8TD UT WOS:000383208700010 PM 26759125 ER PT J AU Hofmarcher, MM Festl, E Bishop-Tarver, L AF Hofmarcher, Maria M. Festl, Eva Bishop-Tarver, Leslie TI Health sector employment growth calls for improvements in labor productivity SO HEALTH POLICY LA English DT Article DE Health workforce; Productivity; Delivery models ID UNITED-KINGDOM; CARE; EXPENDITURE; INSURANCE; EDUCATION; SERVICES; LESSONS; DISEASE; REFORM; STATES AB While rising costs of healthcare have put increased fiscal pressure on public finance, job growth in the health sector has had a stabilizing force on overall employment levels not least in times of economic crises. In 2014 EU-15 countries employed 21 million people in the health and social care sector. Between 2000 and 2014 the share of employed persons in this sector rose from 9.5% to 12.5% of the total labor force in EU-15 countries. Over time labor input growth has shifted towards residential care activities and social work while labor in human health activities including hospitals and ambulatory care still comprises the major share. About half of the human health labor force works in hospital. Variation of health and social care employment is large even in countries with generally comparable institutional structures. While standard measures of productivity in health and social care are not yet comparable across countries, we argue that labor productivity of a growing health work force needs more attention. The long-term stability of the health system will require care delivery models that better utilize a growing health work force in concert with smart investments in digital infrastructure to support this transition. In light of this, more research is needed to explain variations in health and social care labor endowments, to identify effective policy measures of labor productivity enhancement including enhanced efforts to develop comparable productivity indicators in these areas. (C) 2016 Elsevier Ireland Ltd. All rights reserved. C1 [Hofmarcher, Maria M.] HealthSystemIntelligence, Josefstadterstr 14, A-1080 Vienna, Austria. [Hofmarcher, Maria M.] Med Univ Vienna, Dept Hlth Econ, Kinderspitalgasse 15-1, A-1090 Vienna, Austria. [Festl, Eva] Kenyongasse 18, A-1070 Vienna, Austria. [Bishop-Tarver, Leslie] Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St, Boston, MA 02114 USA. RP Hofmarcher, MM (reprint author), HealthSystemIntelligence, Josefstadterstr 14, A-1080 Vienna, Austria.; Hofmarcher, MM (reprint author), Med Univ Vienna, Dept Hlth Econ, Kinderspitalgasse 15-1, A-1090 Vienna, Austria. EM maria.hofmarcher@healthsystemintelligence.eu; evafestl@hotmail.com; lbishop@post.harvard.edu NR 81 TC 0 Z9 0 U1 8 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8510 EI 1872-6054 J9 HEALTH POLICY JI Health Policy PD AUG PY 2016 VL 120 IS 8 BP 894 EP 902 DI 10.1016/j.healthpol.2016.06.001 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA DW0DC UT WOS:000383310100006 PM 27370916 ER PT J AU Salahuddin, S Wenger, JB Zhang, DS Thadhani, R Karumanchi, SA Rana, S AF Salahuddin, Saira Wenger, Julia B. Zhang, Dongsheng Thadhani, Ravi Karumanchi, S. Ananth Rana, Sarosh TI KRYPTOR-automated angiogenic factor assays and risk of preeclampsia-related adverse outcomes SO HYPERTENSION IN PREGNANCY LA English DT Article DE Adverse maternal and perinatal outcomes; angiogenic factors; hypertension; KRYPTOR assay; proteinuria; suspected preeclampsia; triage ID PLACENTAL GROWTH-FACTOR; SUSPECTED PREECLAMPSIA; ANTIANGIOGENIC FACTORS; WOMEN; HYPERTENSION; BIOMARKERS; DIAGNOSIS; PREGNANCY; DISEASE AB Objective: To evaluate KRYPTOR assays for circulating soluble fms-like tyrosine kinase-1 (sFlt1) and placental growth factor (PlGF) in risk assessment of adverse outcomes in women with suspected preeclampsia. Methods: We studied 412 women carrying a singleton pregnancy from a previous study cohort who were evaluated for suspected preeclampsia. Another 434 nonpreeclamptic patients with plasma samples drawn throughout pregnancy were used to derive normative data. Plasma sFlt1 and PlGF levels were measured on the automated KRYPTOR platform and evaluated for prediction of adverse maternal and perinatal outcomes within 2 weeks. Normative values were used to create a ratio of markers and these values were reported as multiples of median (MoM) for women with and without adverse outcomes. The KRYPTOR assay results were also compared with previously reported measurements obtained using the automated Elecsys platform. Results: Among participants presenting at <34 weeks (N = 110), patients with subsequent adverse outcome had higher sFlt1, lower PlGF, and higher sFlt1/PlGF ratio compared with women without adverse outcomes: the median (25th, 75th centile) sFlt1 (pg/ml), 9030 (3197, 12,140) versus 1976 (1248, 2937); PlGF (pg/ml), 36 (16, 111) versus 318 (108, 629); and ratio, 285.6 (32.2, 758.5) versus 6.1 (2.3, 20.3) (all p < 0.0001). Higher sFlt1/PlGF ratio correlated negatively with timing of delivery (r = -0.60, p < 0.001) and the risk of adverse outcomes was markedly elevated among women in highest tertile compared with lower tertile (odds ratio, 14.77; 95% confidence interval (CI), 4.28-51.00). The addition of sFlt1/PlGF ratio (85) to hypertension and proteinuria significantly improved the prediction for subsequent adverse outcomes (AUC 0.89 (95% CI): 0.82, 0.95) for hypertension, proteinuria, and sFlt1/PlGF (AUC = 0.75 (0.65, 0.85)) for hypertension alone (p = 0.002). Compared with normative controls, women who were evaluated for preeclampsia without adverse outcomes had higher MoM for sFlt1/PlGF ratio; these values were further elevated in women with adverse outcomes. sFlt1/PlGF ratios measured on the KRYPTOR platform were highly correlated with measurements obtained using Elecys platform (r = 0.97, p < 0.001). Conclusions: In women with suspected preeclampsia presenting prior to 34 weeks of gestation, KRYPTOR assays for circulating sFlt1 and PlGF when used in conjunction with standard clinical evaluation performs well in the prediction of adverse maternal and perinatal outcomes occurring within 2 weeks of presentation. C1 [Salahuddin, Saira; Karumanchi, S. Ananth; Rana, Sarosh] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02215 USA. [Salahuddin, Saira; Wenger, Julia B.; Zhang, Dongsheng; Thadhani, Ravi; Karumanchi, S. Ananth; Rana, Sarosh] Harvard Med Sch, Boston, MA USA. [Wenger, Julia B.; Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Zhang, Dongsheng; Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Ctr Vasc Biol, Boston, MA 02215 USA. [Zhang, Dongsheng; Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Div Nephrol, Boston, MA 02215 USA. [Rana, Sarosh] Univ Chicago, Dept Obstet & Gynecol, Div Maternal Fetal Med, Chicago, IL 60637 USA. RP Karumanchi, SA (reprint author), Beth Israel Deaconess Med Ctr, 99 Brookline Ave,RN 363, Boston, MA 02215 USA. EM sananth@bidmc.harvard.edu FU NIH [K24]; Howard Hughes Medical Institute; ThermoFisher Scientific FX Ravi Thadhani received funding from K24 award from NIH and S. Ananth Karumanchi was supported by Howard Hughes Medical Institute and has received grant support from ThermoFisher Scientific. NR 27 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1064-1955 EI 1525-6065 J9 HYPERTENS PREGNANCY JI Hypertens. Pregnancy PD AUG PY 2016 VL 35 IS 3 BP 330 EP 345 DI 10.3109/10641955.2016.1148162 PG 16 WC Obstetrics & Gynecology; Physiology; Peripheral Vascular Disease SC Obstetrics & Gynecology; Physiology; Cardiovascular System & Cardiology GA DV5KN UT WOS:000382966100007 PM 27028795 ER PT J AU James-Todd, T Cohen, A Wenger, J Brown, F AF James-Todd, Tamarra Cohen, Allison Wenger, Julia Brown, Florence TI Time-specific placental growth factor (PlGF) across pregnancy and infant birth weight in women with preexisting diabetes SO HYPERTENSION IN PREGNANCY LA English DT Article DE Angiogenic factors; macrosomia; placenta; pregnancy ID CIRCULATING ANGIOGENIC FACTORS; GLUCOSE-LEVELS; FETAL-GROWTH; TYPE-1; SERUM; MACROSOMIA; PREECLAMPSIA; MELLITUS; OUTCOMES; RISK AB Objective: Determine the independent association between time-specific placental growth factor (PIGF)a marker of placental vasculatureand infant birth weight in offspring of mothers with preexisting type 1 and 2 diabetes. Methods: A total of 150 women were recruited from Joslin Diabetes Center's/Beth Israel Deaconess Medical Center's Diabetes in Pregnancy Program. PlGF was measured up to four times during pregnancy. Infant birth weight and covariate data were collected from medical records. Hemoglobin A1c was assessed from drawn blood samples. We used generalized linear and log-binomial models to calculate the change in continuous birth weight, as well as macrosomia for every unit change in time-specific ln-transformed PlGF, respectively. Models were adjusted for potential confounders. Results: Approximately 75% of women had type 1 diabetes. Third trimester PlGF levels were significantly associated with infant birth weight (r = 0.24, p = 0.02 at 27-34 weeks; r = 0.26, p < 0.009 for 36-40 weeks). After full adjustment, there was a 6.1% and 6.6% increase in birth weight for gestational age percentile for each unit increase in ln-transformed PlGF level at 27-34 weeks and 35-40 weeks, respectively (95% CI for 27-34 weeks gestation: 1.1, 11.0, and 95% CI for 35-40 weeks gestation: 0.7%, 12.5%). We found a statistically significant increased risk of macrosomia among women with higher ln-transformed PlGF levels (RR: 1.72; 95% CI: 1.09, 2.70). Associations were not mediated by hemoglobin A1c. Conclusions: Third trimester PlGF levels were associated with higher birth weight in women with preexisting diabetes. These findings may provide insight to the pathophysiology of fetal overgrowth in women with diabetes. C1 [James-Todd, Tamarra] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Dept Epidemiol, Boston, MA USA. [Cohen, Allison; Brown, Florence] Joslin Diabet Ctr, Adult Diabet Sect, One Joslin Pl, Boston, MA 02215 USA. [Cohen, Allison; Wenger, Julia; Brown, Florence] Harvard Med Sch, One Joslin Pl, Boston, MA 02215 USA. [Wenger, Julia] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. RP Brown, F (reprint author), Joslin Diabet Ctr, Adult Diabet Sect, One Joslin Pl, Boston, MA 02215 USA.; Brown, F (reprint author), Harvard Med Sch, One Joslin Pl, Boston, MA 02215 USA. EM Florence.Brown@joslin.harvard.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [K12HD051959]; Department of Medicine Seed funds from the Clinical Investigator Training Program: Beth Israel Deaconess Medical Center - Harvard/MIT 290 Health Sciences and Technology FX This study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12HD051959) and the Department of Medicine Seed funds from the Clinical Investigator Training Program: Beth Israel Deaconess Medical Center - Harvard/MIT 290 Health Sciences and Technology. NR 26 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1064-1955 EI 1525-6065 J9 HYPERTENS PREGNANCY JI Hypertens. Pregnancy PD AUG PY 2016 VL 35 IS 3 BP 436 EP 446 DI 10.3109/10641955.2016.1172085 PG 11 WC Obstetrics & Gynecology; Physiology; Peripheral Vascular Disease SC Obstetrics & Gynecology; Physiology; Cardiovascular System & Cardiology GA DV5KN UT WOS:000382966100017 PM 27336414 ER PT J AU Hope, WW Walsh, TJ Goodwin, J Peloquin, CA Howard, A Kurtzberg, J Mendizabal, A Confer, DL Bulitta, J Baden, LR Neely, MN Wingard, JR AF Hope, William W. Walsh, Thomas J. Goodwin, Joanne Peloquin, Charles A. Howard, Alan Kurtzberg, Joanne Mendizabal, Alan Confer, Dennis L. Bulitta, Jurgen Baden, Lindsey R. Neely, Michael N. Wingard, John R. CA Blood Marrow Transplant Clinical TI Voriconazole pharmacokinetics following HSCT: results from the BMT CTN 0101 trial SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article ID STEM-CELL TRANSPLANTATION; FUNGAL-INFECTIONS; AMPHOTERICIN-B; ASPERGILLOSIS; PROPHYLAXIS; FLUCONAZOLE; POSACONAZOLE; PHARMACODYNAMICS; ITRACONAZOLE; GUIDELINES AB Voriconazole is a first-line agent for the prevention and treatment of a number of invasive fungal diseases. Relatively little is known about the relationship between drug exposure and the prevention of invasive fungal infections. A pharmacokinetic-pharmacodynamic substudy was performed as part of the BMT CTN 0101 trial, which was a randomized clinical trial comparing voriconazole with fluconazole for the prevention of invasive fungal infections in HSCT recipients. A previously described population pharmacokinetic model was used to calculate the maximum a posteriori Bayesian estimates for 187 patients. Drug exposure in each patient was quantified in terms of the average AUC and average trough concentrations. The relationship between drug exposure and the probability of breakthrough infection was investigated using logistic regression. AUC and trough concentrations in patients with and without breakthrough infection were compared. Pharmacokinetic data from each patient were readily described using the maximum a posteriori Bayesian estimates. There were only five patients that had a breakthrough infection while receiving voriconazole in the first 100 days post-HSCT. For these patients, there was no statistically significant relationship between the average AUC or average trough concentration and the probability of breakthrough infection [OR (95% CI) 1.026 (0.956-1.102) and 1.108 (0.475-2.581), respectively]. P value for these estimates was 0.474 and 0.813, respectively. Given the very small number of proven/probable infections, it was difficult to identify any differences in drug exposure in HSCT recipients with and without breakthrough fungal infections. C1 [Hope, William W.; Goodwin, Joanne] Univ Liverpool, Dept Mol & Clin Pharmacol, Liverpool, Merseyside, England. [Walsh, Thomas J.] Cornell Univ, Transplantat Oncol Infect Dis Program, Weill Cornell Med, Dept Med, New York, NY 10021 USA. [Walsh, Thomas J.] Cornell Univ, Transplantat Oncol Infect Dis Program, Weill Cornell Med, Dept Pediat, New York, NY 10021 USA. [Walsh, Thomas J.] Cornell Univ, Transplantat Oncol Infect Dis Program, Weill Cornell Med, Dept Microbiol & Immunol, New York, NY 10021 USA. [Peloquin, Charles A.; Wingard, John R.] Univ Florida, Gainesville, FL USA. [Howard, Alan] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA. [Kurtzberg, Joanne] Duke Univ, Durham, NC USA. [Mendizabal, Alan] Emmes Corp, Rockville, MD USA. [Confer, Dennis L.] Natl Marrow Donor Program, Minneapolis, MN USA. [Bulitta, Jurgen] Univ Florida, Coll Pharm, Dept Pharmaceut, Ctr Pharmacometr & Syst Pharmacol, Orlando, FL USA. [Baden, Lindsey R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Neely, Michael N.] Univ Southern Calif, Los Angeles, CA USA. RP Hope, WW (reprint author), Univ Liverpool, Dept Mol & Clin Pharmacol, Liverpool, Merseyside, England. EM william.hope@liverpool.ac.uk OI Hope, William/0000-0001-6187-878X FU University of Liverpool; National Institutes of Health Research (NIHR) in the UK; National Institutes of Health [R01 HD070886, R01 GM068968] FX This study was supported by internal funding from the University of Liverpool. W. W. H. is supported by a Clinician Scientist Award from the National Institutes of Health Research (NIHR) in the UK. T. J. W. is a Scholar of the Henry Schueler Foundation, an Investigator of Pediatric Infectious Diseases of the Sharp Family Foundation and a Scholar of the Save our Sick Kids Foundation. M. N. N. is supported by National Institutes of Health R01 HD070886 and R01 GM068968. NR 25 TC 1 Z9 1 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 EI 1460-2091 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD AUG PY 2016 VL 71 IS 8 BP 2234 EP 2240 DI 10.1093/jac/dkw127 PG 7 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA DV9GU UT WOS:000383249500027 PM 27121401 ER PT J AU Josephs, K Hu, W Hillis, A Dickerson, B Graff-Radford, N Davis, C Akinyemi, R Ogunniyi, A Taner, N Graff-Radford, J Ali, A Tang-Wai, D Wicklund, M Pasquier, F Lebert, F Snowden, J Fox, N Grossman, M Onyike, C AF Josephs, K. Hu, W. Hillis, A. Dickerson, B. Graff-Radford, N. Davis, C. Akinyemi, R. Ogunniyi, A. Taner, N. Graff-Radford, J. Ali, A. Tang-Wai, D. Wicklund, M. Pasquier, F. Lebert, F. Snowden, J. Fox, N. Grossman, M. Onyike, C. TI Frontotemporal dementia in patients of African descent SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Josephs, K.; Graff-Radford, J.] Mayo Clin, Neurol, Rochester, MN USA. [Hu, W.] Emory Univ, Sch Med, Neurol, Atlanta, GA USA. [Hillis, A.; Davis, C.] Johns Hopkins Med, Neurol, Baltimore, MD USA. [Dickerson, B.] Massachusets Gen Hosp, Neurol, Boston, MA USA. [Graff-Radford, N.; Taner, N.] Mayo Clin, Neurol, Jacksonville, FL 32224 USA. [Akinyemi, R.; Ogunniyi, A.] Univ Ibadan, Neurol, Ibadan, Nigeria. [Ali, A.] Univ Hosp West Indies, Neurol, Mona, Jamaica. [Tang-Wai, D.] Univ Toronto, Neurol, Toronto, ON, Canada. [Wicklund, M.] Univ Florida, Neurol, Gainesville, FL USA. [Pasquier, F.; Lebert, F.] Ctr Hosp Reg & Univ Lille, Neurol, Lille, France. [Snowden, J.] Univ Manchester, Neurol, Manchester, Lancs, England. [Fox, N.] UCL, Inst Neurol, London, England. [Grossman, M.] Univ Penn, Neurol, Philadelphia, PA 19104 USA. [Onyike, C.] Johns Hopkins Med, Neuropsychiat, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA DB6 BP 229 EP 229 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400028 ER PT J AU Dick, KM Boeve, BF Borroni, B Boxer, A Brice, A Butler, CR Couratier, P Dickerson, BC Ducharme, S Finger, E Galimberti, D Gerhard, A Ghoshal, N Graff, C Grossman, M Hodges, JR Huey, ED Laforce, R Le Ber, I Levin, J Mackenzie, R Masellis, M Martinaud, O Mendonca, A Moreno, F Nicholas, M Onyike, CU Otto, M Roberson, ED Rogalski, E Rosen, HJ Rowe, JB Sanchez-Valle, R Santana, I Sorbi, S van Swieten, J Synofzik, M Tagliavini, F Vandenberghe, R Roher, JD AF Dick, K. M. Boeve, B. F. Borroni, B. Boxer, A. Brice, A. Butler, C. R. Couratier, P. Dickerson, B. C. Ducharme, S. Finger, E. Galimberti, D. Gerhard, A. Ghoshal, N. Graff, C. Grossman, M. Hodges, J. R. Huey, E. D. Laforce, R., Jr. Le Ber, I. Levin, J. Mackenzie, R. Masellis, M. Martinaud, O. Mendonca, A. Moreno, F. Nicholas, M. Onyike, C. U. Otto, M. Roberson, E. D. Rogalski, E. Rosen, H. J. Rowe, J. B. Sanchez-Valle, R. Santana, I. Sorbi, S. van Swieten, J. Synofzik, M. Tagliavini, F. Vandenberghe, R. Roher, J. D. TI Symptom onset in genetic frontotemporal dementia SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Dick, K. M.; Nicholas, M.; Roher, J. D.] UCL, Inst Neurol, Dementia Res Ctr, London, England. [Boeve, B. F.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Boeve, B. F.] Mayo Clin, Ctr Sleep Med, Rochester, MN USA. [Borroni, B.] Univ Brescia, Dept Med & Expt Sci, Neurol Unit, Brescia, Italy. [Boxer, A.; Rosen, H. J.] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA. [Brice, A.] Univ Paris 06, Ctr Rech, Inst Cerveau & Moelle Epiniere, Paris, France. [Butler, C. R.] Univ Oxford, Nuffield Dept Clin Neurosci, Oxford, England. [Couratier, P.] CHU Dupuytren, Serv Neurol, Limoges, France. [Dickerson, B. C.] Massachusetts Gen Hosp, Dept Neurol, Frontotemporal Disorders Unit, Charlestown, MA USA. [Dickerson, B. C.] Harvard Med Sch, Charlestown, MA USA. [Ducharme, S.] McGill Univ, McConnell Brain Imaging Ctr, Montreal Neurol Inst, 3801 Univ St, Montreal, PQ, Canada. [Finger, E.] Univ Western Ontario, Dept Clin Neurol Sci, London, ON, Canada. [Galimberti, D.] Univ Milan, Dept Physiopathol & Transplantat, Ist Ricovero & Cura Carattere Sci Osped Policlin, Neurol Unit,Fdn Ca Granda, Milan, Italy. [Gerhard, A.] Univ Manchester, Wolfson Mol Imaging Ctr, Manchester, Lancs, England. [Ghoshal, N.] Washington Univ, Sch Med, St Louis, MO USA. [Graff, C.] Karolinska Inst, Div Neurogeriatr, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden. [Graff, C.] Karolinska Univ Hosp, Dept Geriatr Med, Genet Unit, Stockholm, Sweden. [Grossman, M.] Univ Penn, Penn Frontotemporal Degenerat Ctr, Dept Neurol, Philadelphia, PA 19104 USA. [Hodges, J. R.] Neurosci Res Australia, Sydney, NSW, Australia. [Hodges, J. R.] Australian Res Council Ctr Excellence Cognit & It, Sydney, NSW, Australia. [Hodges, J. R.] Univ New South Wales, Sch Med Sci, Sydney, NSW, Australia. [Huey, E. D.] Columbia Univ, Dept Psychiat, New York, NY USA. [Huey, E. D.] Columbia Univ, Dept Neurol, New York, NY USA. [Laforce, R., Jr.] Univ Laval, Clin Interdisciplinaire Memoire, Dept Sci Neurol, Hop Enfant Jesus, Quebec City, PQ G1K 7P4, Canada. [Laforce, R., Jr.] Univ Laval, Fac Med, Quebec City, PQ G1K 7P4, Canada. [Le Ber, I.] Univ Paris 06, Sorbonne Univ, Inst Cerveau & Moelle Epiniere ICM, CNRS,INSERM,U1127,UMR 7225,UMR S 1127,Hop Pitie S, Paris, France. [Le Ber, I.] Hop La Pitie Salpetriere, AP HP, Ctr Reference Demences Rares, Paris, France. [Levin, J.] Univ Munich, Neurol Dept, Marchioninistr, Munich, Germany. [Mackenzie, R.] Univ British Columbia, Dept Pathol & Lab Med, Div Neuropathol, Vancouver, BC V5Z 1M9, Canada. [Masellis, M.] Univ Toronto, Sunnybrook Res Inst, Div Neurol, LC Campbell Cognit Neurol Res Unit,Dept Med,Sunny, Toronto, ON, Canada. [Martinaud, O.] Rouen Univ Hosp, Dept Neurol, Rouen, France. [Mendonca, A.] Inst Mol Med, Lab Neurosci, Lisbon, Portugal. [Moreno, F.] Univ Basque Country, Inst Biodonostia, Neurosci Area, San Sebastian, Spain. [Moreno, F.] Univ Basque Country, Dept Neurosci, San Sebastian, Spain. [Nicholas, M.] London Sch Hyg & Trop Med, Dept Med Stat, London, England. [Onyike, C. U.] Johns Hopkins Univ, Baltimore, MD USA. [Otto, M.] Univ Ulm, Dept Neurol, Ulm, Germany. [Roberson, E. D.] Center Neurodegenerat & Expt Therapeut, Dept Neurol, Birmingham, AL USA. [Roberson, E. D.] Center Neurodegenerat & Expt Therapeut, Dept Neurobiol, Birmingham, AL USA. [Rogalski, E.] Northwestern Univ, Cognit Neurol, Evanston, IL 60208 USA. [Rogalski, E.] Northwestern Univ, Alzheimers Dis Ctr, Evanston, IL 60208 USA. [Rowe, J. B.] Univ Cambridge, Dept Clin Neurosci, Cambridge, England. [Sanchez-Valle, R.] Hosp Clin Barcelona, Alzheimers Dis & Other Cognit Disorders Unit, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain. [Santana, I.] Univ Coimbra, Ctr Neurosci & Cell Biol, Coimbra, Portugal. [Sorbi, S.] Univ Florence, Dept Neurosci Psychol Drug Res & Child Hlth, Florence, Italy. [van Swieten, J.] Erasmus MC, Dept Neurol, Rotterdam, Netherlands. [Synofzik, M.] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, Tubingen, Germany. [Synofzik, M.] German Res Ctr Neurodegenerat Dis DZNE, Tubingen, Germany. [Tagliavini, F.] Fdn Ist Ricovero & Cura Carattere Sci, Ist Neurol Carlo Besta, Milan, Italy. [Vandenberghe, R.] Univ Leuven, Dept Neurol, Lab Cognit Neurol, Leuven, Belgium. [Vandenberghe, R.] Univ Hosp Leuven Gasthuisberg, Leuven, Belgium. RI Levin, Johannes/E-4052-2010 OI Levin, Johannes/0000-0001-5092-4306 NR 0 TC 0 Z9 0 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA DB8 BP 232 EP 233 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400033 ER PT J AU Taylor, L McMillan, P Liachko, N Saxton, A Strovas, T Kraemer, B AF Taylor, L. McMillan, P. Liachko, N. Saxton, A. Strovas, T. Kraemer, B. TI TTBK1/2 hyper-activation drives pTau and pTDP accumulation SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Taylor, L.; Kraemer, B.] Univ Washington, Med Gerontol & Geriatr Med, Seattle, WA 98195 USA. [McMillan, P.; Liachko, N.; Saxton, A.; Strovas, T.; Kraemer, B.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Saxton, A.; Kraemer, B.] Seattle Inst Biomed & Clin Res, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA DB11 BP 236 EP 236 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400041 ER PT J AU Fong, SS Navarrete, CD Perfecto, SE Carr, AR Jimenez, EE Mendez, MF AF Fong, S. S. Navarrete, C. D. Perfecto, S. E. Carr, A. R. Jimenez, E. E. Mendez, M. F. TI Emotion and moral dilemmas in behavioral variant frontotemporal dementia SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Fong, S. S.; Perfecto, S. E.; Jimenez, E. E.; Mendez, M. F.] Univ Calif Los Angeles, Los Angeles, CA USA. [Fong, S. S.; Carr, A. R.; Jimenez, E. E.; Mendez, M. F.] VA Greater Los Angeles Healthcare Ctr, Neurol, Los Angeles, CA USA. [Navarrete, C. D.] Michigan State Univ, Psychol, E Lansing, MI 48824 USA. [Mendez, M. F.] Univ Calif Los Angeles, Psychiat & Biobehav Sci, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P55 BP 264 EP 265 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400111 ER PT J AU Paholpak, P Li-Jung, L Carr, DR Jimenez, E Barrows, RJ Sabodash, V Mendez, MF AF Paholpak, P. Li-Jung, L. Carr, D. R. Jimenez, E. Barrows, R. J. Sabodash, V. Mendez, M. F. TI Prolonged visual facial gaze in frontotemporal dementia SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Paholpak, P.] Khon Kaen Univ, Psychiat, Khon Kaen, Thailand. [Paholpak, P.; Carr, D. R.; Jimenez, E.; Barrows, R. J.; Sabodash, V.; Mendez, M. F.] Univ Calif Los Angeles, Neurol, Los Angeles, CA USA. [Paholpak, P.; Jimenez, E.; Barrows, R. J.; Sabodash, V.; Mendez, M. F.] Greater Los Angeles VA Healthcare Syst, Neurol, Los Angeles, CA USA. [Li-Jung, L.] Univ Calif Los Angeles, Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P53 BP 264 EP 264 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400109 ER PT J AU Paholpak, P Carr, DR Barsuglia, JP Barrows, RJ Jimenez, E Lee, GJ Mendez, MF AF Paholpak, P. Carr, D. R. Barsuglia, J. P. Barrows, R. J. Jimenez, E. Lee, G. J. Mendez, M. F. TI Person-based vs. generalized impulsivity disinhibition in frontotemporal dementia and Alzheimer's disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Paholpak, P.] Khon Kaen Univ, Psychiat, Khon Kaen, Thailand. [Paholpak, P.; Carr, D. R.; Barrows, R. J.; Jimenez, E.; Mendez, M. F.] Univ Calif Los Angeles, Neurol, Los Angeles, CA USA. [Paholpak, P.; Carr, D. R.; Barsuglia, J. P.; Barrows, R. J.; Jimenez, E.; Mendez, M. F.] Greater Los Angeles VA Healthcare Syst, Neurol, Los Angeles, CA USA. [Lee, G. J.] Loma Linda Univ, Psychol, Loma Linda, CA 92350 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 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P54 BP 264 EP 264 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400110 ER PT J AU Boeve, B Rosen, H Boxer, A Coppola, G Dheel, C Dickerson, B Faber, K Fields, J Foroud, T Gavrilova, R Ghoshal, N Goldman, J Graff-Radford, N Grossman, M Heuer, H Hsiao, J Hsiung, R Huey, E Irwin, D Kantarci, K Karydas, A Knopman, D Kornak, J Kramer, J Kukull, W Mackenzie, I Miller, B Phelps, C Rademakers, R Rankin, K Shaw, L Sutherland, M Toga, A Trojanowski, J Vetor, A Weintraub, S Wszolek, Z AF Boeve, B. Rosen, H. Boxer, A. Coppola, G. Dheel, C. Dickerson, B. Faber, K. Fields, J. Foroud, T. Gavrilova, R. Ghoshal, N. Goldman, J. Graff-Radford, N. Grossman, M. Heuer, H. Hsiao, J. Hsiung, R. Huey, E. Irwin, D. Kantarci, K. Karydas, A. Knopman, D. Kornak, J. Kramer, J. Kukull, W. Mackenzie, I. Miller, B. Phelps, C. Rademakers, R. Rankin, K. Shaw, L. Sutherland, M. Toga, A. Trojanowski, J. Vetor, A. Weintraub, S. Wszolek, Z. TI Similar findings on clinical and neuropsychological measures in asymptomatic mutation versus non-mutation carriers: preliminary data from LEFFTDS SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Boeve, B.; Dheel, C.; Fields, J.; Gavrilova, R.; Kantarci, K.; Knopman, D.] Mayo Clin, Rochester, MN USA. [Rosen, H.; Boxer, A.; Heuer, H.; Karydas, A.; Kornak, J.; Kramer, J.; Miller, B.; Rankin, K.] UCSF, San Francisco, CA USA. [Coppola, G.] UCLA, Los Angeles, CA USA. [Dickerson, B.] Massachusetts Gen Hosp, Boston, MA USA. [Faber, K.; Foroud, T.; Vetor, A.] Indiana Univ, Indianapolis, IN USA. [Ghoshal, N.; Graff-Radford, N.] Washington Univ, St Louis, MO USA. [Goldman, J.; Huey, E.] Columbia Univ, New York, NY USA. [Graff-Radford, N.; Rademakers, R.; Wszolek, Z.] Mayo Clin, Jacksonville, FL USA. [Grossman, M.; Irwin, D.; Shaw, L.; Trojanowski, J.] Univ Penn, Philadelphia, PA USA. [Hsiao, J.; Phelps, C.] NIA, Bethesda, MD USA. [Hsiung, R.; Mackenzie, I.] Univers British Columbia, Vancouver, BC, Canada. [Kukull, W.] Univ Washington, Seattle, WA USA. [Sutherland, M.] NINDS, Bethesda, MD USA. [Toga, A.] USC, LONI, Los Angeles, CA USA. [Weintraub, S.] Northwestern Univ, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P118 BP 287 EP 287 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400173 ER PT J AU Rosen, H Boeve, B Boxer, A Coppola, G Dheel, C Dickerson, B Faber, K Fields, J Faroud, T Gavrilova, R Ghoshal, N Goldman, J Graff-Radford, N Grossman, M Heuer, H Hsiao, J Hsiung, GYR Huey, ED Irwin, D Kantarci, K Karydas, A Knopman, D Kornak, J Kramer, J Kukull, W Mackenzie, I Miller, B Phelps, C Rademakers, R Rankin, K Shaw, L Sutherland, M Toga, A Trojanowski, J Vetor, A Weintraub, S Wszolek, Z AF Rosen, H. Boeve, B. Boxer, A. Coppola, G. Dheel, C. Dickerson, B. Faber, K. Fields, J. Faroud, T. Gavrilova, R. Ghoshal, N. Goldman, J. Graff-Radford, N. Grossman, M. Heuer, H. Hsiao, J. Hsiung, G. -Y. R. Huey, E. D. Irwin, D. Kantarci, K. Karydas, A. Knopman, D. Kornak, J. Kramer, J. Kukull, W. Mackenzie, I. Miller, B. Phelps, C. Rademakers, R. Rankin, K. Shaw, L. Sutherland, M. Toga, A. Trojanowski, J. Vetor, A. Weintraub, S. Wszolek, Z. TI Differences on neuropsychiatric measures in asymptomatic (CDR=0) versus mildly symptomatic (CDR=0.5) mutation carriers: preliminary data from LEFFTDS SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Rosen, H.; Heuer, H.; Karydas, A.; Kornak, J.; Kramer, J.; Miller, B.; Rankin, K.] Univ Calif San Francisco, Neurol, San Francisco, CA 94143 USA. [Boeve, B.; Dheel, C.; Fields, J.; Gavrilova, R.; Kantarci, K.; Knopman, D.] Mayo Clin, Rochester, MN USA. [Coppola, G.; Toga, A.] Univ Calif Los Angeles, Los Angeles, CA USA. [Dickerson, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Faber, K.; Faroud, T.] Indiana Univ, Indianapolis, IN 46204 USA. [Ghoshal, N.; Vetor, A.] Washington Univ, St Louis, MO USA. [Goldman, J.] Columbia Univ, New York, NY USA. [Graff-Radford, N.; Rademakers, R.; Wszolek, Z.] Mayo Clin, Jacksonville, FL 32224 USA. [Grossman, M.; Irwin, D.; Shaw, L.; Trojanowski, J.] Univ Penn, Philadelphia, PA 19104 USA. [Hsiao, J.; Phelps, C.] NIA, Bethesda, MD 20892 USA. [Hsiung, G. -Y. R.; Mackenzie, I.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Kukull, W.] Univ Washington, Seattle, WA 98195 USA. [Sutherland, M.] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Weintraub, S.] Norhtwestern Univ, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P119 BP 287 EP 287 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400174 ER PT J AU Kramer, J Weintraub, S Boeve, B Rosen, H Boxer, A Coppola, G Dheel, C Dickerson, B Faber, K Fields, J Faroud, T Gavrilova, R Ghoshal, N Goldman, J Graff-Radford, N Grossman, M Heuer, H Hsiao, J Hsiung, R Huey, E Irwin, D Kantarci, K Karydas, A Knopman, D Kornak, J Kukull, W Mackenzie, I Miller, B Phelps, C Rademakers, R Rankin, K Shaw, L Sutherland, M Toga, A Trojanowski, J Vetor, A Wszolek, Z AF Kramer, J. Weintraub, S. Boeve, B. Rosen, H. Boxer, A. Coppola, G. Dheel, C. Dickerson, B. Faber, K. Fields, J. Faroud, T. Gavrilova, R. Ghoshal, N. Goldman, J. Graff-Radford, N. Grossman, M. Heuer, H. Hsiao, J. Hsiung, R. Huey, E. Irwin, D. Kantarci, K. Karydas, A. Knopman, D. Kornak, J. Kukull, W. Mackenzie, I. Miller, B. Phelps, C. Rademakers, R. Rankin, K. Shaw, L. Sutherland, M. Toga, A. Trojanowski, J. Vetor, A. Wszolek, Z. TI Differences on neuropsychological measures in asymptomatic (CDR=0) versus mildly symptomatic (CDR=0.5) mutation carriers: preliminary data from LEFFTDS SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Kramer, J.; Rosen, H.; Boxer, A.; Heuer, H.; Kantarci, K.; Kornak, J.; Miller, B.; Rankin, K.] UCSF, San Francisco, CA USA. [Weintraub, S.] Northwestern, Chicago, IL USA. [Boeve, B.; Dheel, C.; Fields, J.; Gavrilova, R.; Kantarci, K.; Knopman, D.] Mayo Clin, Rochester, MN USA. [Coppola, G.] Univ Calif Los Angeles, Los Angeles, CA USA. [Dickerson, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Faber, K.; Faroud, T.; Vetor, A.] Indiana Univ, Indianapolis, IN 46204 USA. [Ghoshal, N.] Washington Univ, St Louis, MO USA. [Goldman, J.; Huey, E.] Columbia Univ, New York, NY USA. [Graff-Radford, N.; Rademakers, R.; Wszolek, Z.] Mayo Clin, Jacksonville, FL 32224 USA. [Grossman, M.; Irwin, D.; Shaw, L.; Trojanowski, J.] Univ Penn, Philadelphia, PA 19104 USA. [Hsiao, J.; Phelps, C.] NIA, Bethesda, MD 20892 USA. [Hsiung, R.; Mackenzie, I.] Univ British Columbia, Vancouver, BC, Canada. [Kukull, W.] Univ Washington, Seattle, WA 98195 USA. [Sutherland, M.] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Toga, A.] USC, LONI, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P127 BP 290 EP 291 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400182 ER PT J AU Fong, S Mendez, MF AF Fong, S. Mendez, M. F. TI Variables affecting emotional reactivity to socioemotional stimuli in frontotemporal dementia SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Fong, S.; Mendez, M. F.] Univ Calif Los Angeles, Neurol, Los Angeles, CA USA. [Fong, S.; Mendez, M. F.] VA Greater Los Angeles Healthcare Ctr, Neurol, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P148 BP 298 EP 298 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400202 ER PT J AU Rankin, K Kramer, J Rosen, H Boeve, B Boxer, A Coppola, G Dickerson, B Dheel, C Fields, J Gavrilova, R Ghoshal, N Goldman, J Graff-Radford, N Grossman, M Heuer, H Hsiao, J Hsiung, R Huey, E Irwin, D Kantarci, K Karydas, A Kornak, J Knopman, D Kukull, W Mackenzie, I Miller, B Phelps, C Rademakers, R Shaw, L Sutherland, M Toga, A Trojanowski, J Vetor, A Weintraub, S Wszolek, Z AF Rankin, K. Kramer, J. Rosen, H. Boeve, B. Boxer, A. Coppola, G. Dickerson, B. Dheel, C. Fields, J. Gavrilova, R. Ghoshal, N. Goldman, J. Graff-Radford, N. Grossman, M. Heuer, H. Hsiao, J. Hsiung, R. Huey, E. Irwin, D. Kantarci, K. Karydas, A. Kornak, J. Knopman, D. Kukull, W. Mackenzie, I. Miller, B. Phelps, C. Rademakers, R. Shaw, L. Sutherland, M. Toga, A. Trojanowski, J. Vetor, A. Weintraub, S. Wszolek, Z. TI Differences on novel measures of social comportment in asymptomatic (CDR=0) versus mildly symptomatic (CDR=0.5) mutation carriers: preliminary data from LEFFTDS SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Rankin, K.; Kramer, J.; Rosen, H.; Boxer, A.; Heuer, H.; Karydas, A.; Kornak, J.; Miller, B.] Univ Calif San Francisco, Neurol, San Francisco, CA 94143 USA. [Boeve, B.; Dheel, C.; Fields, J.; Gavrilova, R.; Kantarci, K.; Knopman, D.] Mayo Clin, Rochester, MN USA. [Coppola, G.] Univ Calif Los Angeles, Los Angeles, CA USA. [Dickerson, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ghoshal, N.] Washington Univ, St Louis, MO USA. [Goldman, J.; Huey, E.] Columbia Univ, New York, NY USA. [Graff-Radford, N.; Rademakers, R.; Wszolek, Z.] Mayo Clin, Jacksonville, FL 32224 USA. [Grossman, M.; Shaw, L.; Trojanowski, J.] Univ Penn, Philadelphia, PA 19104 USA. [Hsiao, J.; Phelps, C.] NIA, Bethesda, MD 20892 USA. [Hsiung, R.; Mackenzie, I.] Univ British Columbia, Vancouver, BC, Canada. [Kukull, W.] Univ Washington, Seattle, WA 98195 USA. [Sutherland, M.] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Toga, A.] USC LONI, Los Angeles, CA USA. [Vetor, A.] Indiana Univ, Indianapolis, IN 46204 USA. [Weintraub, S.] Northwestern Univ, Chicago, IL 60611 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 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P150 BP 299 EP 299 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400204 ER PT J AU Fong, SS Carr, AR Daianu, M Deutsch, MB Jimenez, EE Juarez, KO Mather, MM Paholpak, P Perfecto, SE Thompson, PM Mendez, MF AF Fong, S. S. Carr, A. R. Daianu, M. Deutsch, M. B. Jimenez, E. E. Juarez, K. O. Mather, M. M. Paholpak, P. Perfecto, S. E. Thompson, P. M. Mendez, M. F. TI The attribution of animacy and agency in frontotemporal dementia vs. Alzheimer's disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Fong, S. S.; Deutsch, M. B.; Jimenez, E. E.; Juarez, K. O.; Mather, M. M.; Paholpak, P.; Perfecto, S. E.; Mendez, M. F.] Univ Calif Los Angeles, Neurol, Los Angeles, CA USA. [Fong, S. S.; Carr, A. R.; Deutsch, M. B.; Jimenez, E. E.; Juarez, K. O.; Mather, M. M.; Paholpak, P.; Mendez, M. F.] VA Greater Los Angeles Healthcare Ctr, Neurol, Los Angeles, CA USA. [Daianu, M.; Thompson, P. M.] Univ Southern Calif, Imaging Genet Ctr, Mark & Mary Stevens Neuroimaging & Informat Inst, Los Angeles, CA USA. [Deutsch, M. B.] Icahn Sch Med Mt Sinai, Neurol, New York, NY 10029 USA. [Paholpak, P.] Khon Kaen Univ, Psychiat, Khon Kaen, Thailand. [Thompson, P. M.] Univ Southern Calif, Psychiat, Los Angeles, CA USA. [Thompson, P. M.] Univ Southern Calif, Radiol, Los Angeles, CA USA. [Thompson, P. M.] Univ Southern Calif, Engn, Los Angeles, CA USA. [Thompson, P. M.] Univ Southern Calif, Pediat, Los Angeles, CA USA. [Thompson, P. M.] Univ Southern Calif, Ophthalmol, Los Angeles, CA USA. [Thompson, P. M.] Univ Southern Calif, Neurol, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P153 BP 300 EP 300 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400207 ER PT J AU Boeve, B Rosen, H Boxer, A Coppola, G Dheel, C Dickerson, B Faber, K Fields, J Foroud, T Gavrilova, R Ghoshal, N Goldman, J Graff-Radford, N Grossman, M Heuer, H Hsiao, J Hsiung, R Huey, E Irwin, D Kantarci, K Karydas, A Knopman, D Kornak, J Kramer, J Kukull, W Mackenzie, I Miller, B Phelps, C Rademakers, R Rankin, K Shaw, L Sutherland, M Toga, A Trojanowski, J Vetor, A Weintraub, S Wszolek, Z AF Boeve, B. Rosen, H. Boxer, A. Coppola, G. Dheel, C. Dickerson, B. Faber, K. Fields, J. Foroud, T. Gavrilova, R. Ghoshal, N. Goldman, J. Graff-Radford, N. Grossman, M. Heuer, H. Hsiao, J. Hsiung, R. Huey, E. Irwin, D. Kantarci, K. Karydas, A. Knopman, D. Kornak, J. Kramer, J. Kukull, W. Mackenzie, I. Miller, B. Phelps, C. Rademakers, R. Rankin, K. Shaw, L. Sutherland, M. Toga, A. Trojanowski, J. Vetor, A. Weintraub, S. Wszolek, Z. TI Characteristics and Progress on the Initial 147 Subjects in the Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) Protocol SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Boeve, B.; Dheel, C.; Fields, J.; Gavrilova, R.; Kantarci, K.; Knopman, D.] Mayo Clin, Rochester, MN USA. [Rosen, H.; Boxer, A.; Heuer, H.; Karydas, A.; Kornak, J.; Kramer, J.; Miller, B.; Rankin, K.] UCSF, San Francisco, CA USA. [Coppola, G.] Univ Calif Los Angeles, Los Angeles, CA USA. [Dickerson, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Faber, K.; Foroud, T.; Vetor, A.] Indiana Univ, Indianapolis, IN 46204 USA. [Ghoshal, N.] Washington Univ, St Louis, MO 63130 USA. [Goldman, J.; Huey, E.] Columbia Univ, New York, NY USA. [Graff-Radford, N.; Rademakers, R.; Wszolek, Z.] Mayo Clin, Jacksonville, FL USA. [Grossman, M.; Irwin, D.; Shaw, L.; Trojanowski, J.] Univ Penn, Philadelphia, PA 19104 USA. [Hsiao, J.; Phelps, C.] NIA, Bethesda, MD 20892 USA. [Hsiung, R.; Mackenzie, I.] Univ British Columbia, Vancouver, BC, Canada. [Kukull, W.] Univ Washington, Seattle, WA 98195 USA. [Sutherland, M.] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Toga, A.] LONI, USC, Los Angeles, CA USA. [Weintraub, S.] Northwestern Univ, Chicago, IL 60611 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 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P172 BP 309 EP 309 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400226 ER PT J AU Knopman, D Boeve, B Rosen, H Boxer, A Coppola, G Dheel, C Dickerson, B Faber, K Fields, J Foroud, T Gavrilova, R Ghoshal, N Goldman, J Graff-Radford, N Grossman, M Heuer, H Hsiao, J Huey, E Hsiung, R Irwin, D Kantarci, K Karydas, A Kornak, J Kramer, J Kukull, W Mackenzie, I Miller, B Phelps, C Rademakers, R Rankin, K Shaw, L Sutherland, M Toga, A Trojanowski, J Weintraub, S Wszolek, Z Vetor, A AF Knopman, D. Boeve, B. Rosen, H. Boxer, A. Coppola, G. Dheel, C. Dickerson, B. Faber, K. Fields, J. Foroud, T. Gavrilova, R. Ghoshal, N. Goldman, J. Graff-Radford, N. Grossman, M. Heuer, H. Hsiao, J. Huey, E. Hsiung, R. Irwin, D. Kantarci, K. Karydas, A. Kornak, J. Kramer, J. Kukull, W. Mackenzie, I. Miller, B. Phelps, C. Rademakers, R. Rankin, K. Shaw, L. Sutherland, M. Toga, A. Trojanowski, J. Weintraub, S. Wszolek, Z. Vetor, A. TI Absence of differences on key measures in mildly (CDR=0.5) versus overtly (CDR >= 1) symptomatic mutation carriers: preliminary data from LEFFTDS SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Knopman, D.; Boeve, B.; Dheel, C.] Mayo Clin, Neurol, Rochester, MN USA. [Rosen, H.; Boxer, A.; Heuer, H.; Karydas, A.; Kornak, J.; Kramer, J.; Miller, B.; Rankin, K.] Univ Calif San Francisco, Neurol, San Francisco, CA 94143 USA. [Coppola, G.] Univ Calif Los Angeles, Los Angeles, CA USA. [Dickerson, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Faber, K.; Foroud, T.; Vetor, A.] Indiana Univ, Indianapolis, IN 46204 USA. [Fields, J.; Gavrilova, R.; Kantarci, K.] Mayo Clin, Rochester, MN USA. [Ghoshal, N.] Washington Univ, St Louis, MO 63130 USA. [Goldman, J.; Huey, E.] Columbia Univ, New York, NY USA. [Graff-Radford, N.; Rademakers, R.; Wszolek, Z.] Mayo Clin, Jacksonville, FL USA. [Grossman, M.; Irwin, D.; Shaw, L.; Trojanowski, J.] Univ Penn, Philadelphia, PA 19104 USA. [Hsiao, J.; Phelps, C.; Sutherland, M.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Hsiung, R.; Mackenzie, I.] Univ British Columbia, Vancouver, BC, Canada. [Kukull, W.] Univ Washington, Seattle, WA 98195 USA. [Toga, A.] LONI, USC, Los Angeles, CA USA. [Weintraub, S.] Northwestern Univ, Chicago, IL 60611 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 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P189 BP 316 EP 316 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400243 ER PT J AU Knopman, D Boeve, B Rosen, H Boxer, A Coppola, G Dheel, C Dickerson, B Faber, K Fields, J Foroud, T Gavrilova, R Ghoshal, N Goldman, J Graff-Radford, N Grossman, M Heuer, H Hsiao, J Hsiung, R Huey, E Irwin, D Kantarci, K Karydas, A Kramer, J Kukull, W Mackenzie, I Miller, B Phelps, C Rademakers, R Rankin, K Shaw, L Sutherland, M Toga, A Trojanowski, J Vetor, A Weintraub, S Wszolek, Z AF Knopman, D. Boeve, B. Rosen, H. Boxer, A. Coppola, G. Dheel, C. Dickerson, B. Faber, K. Fields, J. Foroud, T. Gavrilova, R. Ghoshal, N. Goldman, J. Graff-Radford, N. Grossman, M. Heuer, H. Hsiao, J. Hsiung, R. Huey, E. Irwin, D. Kantarci, K. Karydas, A. Kramer, J. Kukull, W. Mackenzie, I. Miller, B. Phelps, C. Rademakers, R. Rankin, K. Shaw, L. Sutherland, M. Toga, A. Trojanowski, J. Vetor, A. Weintraub, S. Wszolek, Z. TI Differences on clinical measures in asymptomatic (CDR=0) versus mildly symptomatic (CDR=0.5) mutation carriers: preliminary data from LEFFTDS SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Knopman, D.; Boeve, B.; Dheel, C.; Gavrilova, R.] Mayo Clin, Neurol, Rochester, MN USA. [Rosen, H.; Boxer, A.; Heuer, H.; Karydas, A.; Kramer, J.; Miller, B.; Rankin, K.] Univ Calif San Francisco, Neurol, San Francisco, CA 94143 USA. [Coppola, G.] Univ Calif Los Angeles, Los Angeles, CA USA. [Dickerson, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Faber, K.; Foroud, T.; Vetor, A.] Indiana Univ, Indianapolis, IN 46204 USA. [Fields, J.] Mayo Clin, Psychiat, Rochester, MN USA. [Ghoshal, N.] Washington Univ, St Louis, MO 63130 USA. [Goldman, J.; Huey, E.] Columbia Univ, New York, NY USA. [Graff-Radford, N.; Rademakers, R.; Wszolek, Z.] Mayo Clin, Jacksonville, FL USA. [Grossman, M.; Irwin, D.; Shaw, L.; Trojanowski, J.] Univ Penn, Philadelphia, PA 19104 USA. [Hsiao, J.; Phelps, C.; Sutherland, M.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Hsiung, R.; Mackenzie, I.] Univ British Columbia, Vancouver, BC, Canada. [Kantarci, K.] Mayo Clin, Radiol, Rochester, MN USA. [Kukull, W.] Univ Washington, Seattle, WA 98195 USA. [Toga, A.] LONI, USC, Los Angeles, CA USA. [Weintraub, S.] Northwestern Univ, Chicago, IL 60611 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 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P191 BP 317 EP 317 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400245 ER PT J AU Gendron, T van Blitterswijk, M Bieniek, K Daughrity, L Jiang, J Rush, B Pedraza, O Lucas, J Murray, M Desaro, P Robertson, A Overstreet, K Thomas, C Crook, J Castanedes-Casey, M Rousseau, L Josephs, K Parisi, J Knopman, D Petersen, R Boeve, B Graff-Radford, N Rademakers, R Lagier-Tourenne, C Edbauer, D Cleveland, D Dickson, D Petrucelli, L Boylan, K AF Gendron, T. van Blitterswijk, M. Bieniek, K. Daughrity, L. Jiang, J. Rush, B. Pedraza, O. Lucas, J. Murray, M. Desaro, P. Robertson, A. Overstreet, K. Thomas, C. Crook, J. Castanedes-Casey, M. Rousseau, L. Josephs, K. Parisi, J. Knopman, D. Petersen, R. Boeve, B. Graff-Radford, N. Rademakers, R. Lagier-Tourenne, C. Edbauer, D. Cleveland, D. Dickson, D. Petrucelli, L. Boylan, K. TI Cerebellar c9RAN proteins associate with clinical and neuropathological characteristics of C9ORF72 repeat expansion carriers SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Gendron, T.; van Blitterswijk, M.; Bieniek, K.; Daughrity, L.; Murray, M.; Castanedes-Casey, M.; Rousseau, L.; Rademakers, R.; Dickson, D.; Petrucelli, L.] Mayo Clin, Neurosci, Jacksonville, FL 32224 USA. [Jiang, J.; Cleveland, D.] Univ Calif San Diego, Ludwig Inst, La Jolla, CA USA. [Rush, B.; Pedraza, O.; Lucas, J.; Desaro, P.; Robertson, A.; Overstreet, K.; Graff-Radford, N.; Boylan, K.] Mayo Clin, Neurol, Jacksonville, FL 32224 USA. [Thomas, C.; Crook, J.] Mayo Clin, Sect Biostat, Jacksonville, FL 32224 USA. [Josephs, K.; Parisi, J.; Knopman, D.; Petersen, R.; Boeve, B.] Mayo Clin, Neurol, Rochester, MN USA. [Lagier-Tourenne, C.] Massachusetts Gen Hosp, Inst Neurodegenerat Dis, Charlestown, MA USA. [Edbauer, D.] Univ Munich, Inst Metab Biochem, Munich, Germany. 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 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P251 BP 339 EP 340 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400303 ER PT J AU Collins, J Montal, V Gorno-Tempini, ML Dickerson, B AF Collins, J. Montal, V. Gorno-Tempini, M. L. Dickerson, B. TI Focal temporal pole atrophy and network degeneration in semantic variant primary progressive aphasia SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Collins, J.; Dickerson, B.] Massachusetts Gen Hosp, Neurol, Charlestown, MA USA. [Collins, J.; Dickerson, B.] Harvard Med Sch, Charlestown, MA USA. [Montal, V.] Univ Autonoma Barcelona, Neurol, Barcelona, Spain. [Gorno-Tempini, M. L.] Univ Calif San Francisco, Neurol, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P264 BP 345 EP 345 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400316 ER PT J AU Veronelli, L Makaretz, SJ Quimby, M Corbo, M Dickerson, BC AF Veronelli, L. Makaretz, S. J. Quimby, M. Corbo, M. Dickerson, B. C. TI Predictors of conversion to dementia in primary progressive aphasia SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Veronelli, L.; Corbo, M.] Casa Cura Policlin, Dept Neurorehabil Sci, Milan, Italy. [Veronelli, L.; Makaretz, S. J.; Quimby, M.; Dickerson, B. C.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. [Veronelli, L.; Makaretz, S. J.; Quimby, M.; Dickerson, B. C.] Harvard Med Sch, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 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 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P300 BP 357 EP 357 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400352 ER PT J AU Dutt, S Binney, R Heuer, H Luong, P Attygalle, S Bhatt, P Marx, G Elofson, J Tartaglia, MC Litvan, I McGinnis, S Dickerson, B Kornak, J Waltzman, D Voltarelli, L Schuff, N Rabinovici, G Kramer, J Jack, C Miller, B Boxer, A AF Dutt, S. Binney, R. Heuer, H. Luong, P. Attygalle, S. Bhatt, P. Marx, G. Elofson, J. Tartaglia, M. C. Litvan, I. McGinnis, S. Dickerson, B. Kornak, J. Waltzman, D. Voltarelli, L. Schuff, N. Rabinovici, G. Kramer, J. Jack, C. Miller, B. Boxer, A. TI Rapid progression of brain atrophy in progressive supranuclear palsy and corticobasal degeneration SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Dutt, S.; Binney, R.; Heuer, H.; Luong, P.; Attygalle, S.; Bhatt, P.; Marx, G.; Elofson, J.; Waltzman, D.; Voltarelli, L.; Rabinovici, G.; Kramer, J.; Miller, B.; Boxer, A.] UCSF, Neurol, San Francisco, CA USA. [Binney, R.] Temple Univ, Commun Sci & Disorders, Philadelphia, PA 19122 USA. [Tartaglia, M. C.] Univ Toronto, Toronto, ON, Canada. [Litvan, I.] Univ Calif San Diego, Neurosci, San Diego, CA USA. [McGinnis, S.; Dickerson, B.] Massachusetts Gen Hosp, Gerontol, Charlestown, MA USA. [Kornak, J.] UCSF, Epidemiol & Biostat, San Francisco, CA USA. [Waltzman, D.] Stanford Univ, Psychiat & Behav Sci, Stanford, CA 94305 USA. [Schuff, N.] UCSF, Radiol, San Francisco, CA USA. [Jack, C.] Mayo Clin, Radiol, Rochester, MN 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 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P313 BP 363 EP 363 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400365 ER PT J AU Luong, D Voltarelli, L Heuer, H Kornak, J Domoto-Reilly, K Dickerson, B Litvan, I Tartaglia, MC Miller, B Boxer, A AF Luong, D. Voltarelli, L. Heuer, H. Kornak, J. Domoto-Reilly, K. Dickerson, B. Litvan, I. Tartaglia, M. C. Miller, B. Boxer, A. TI Measuring clinical and cognitive decline in CBD and PSP for multicenter clinical trials - the 4-repeat tauopathy neuroimaging initiative (4RTNI) SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Luong, D.; Voltarelli, L.; Heuer, H.; Kornak, J.; Miller, B.; Boxer, A.] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA. [Domoto-Reilly, K.; Dickerson, B.] Massachusetts Gen Hosp, Frontotemporal Disorders Unit, Boston, MA 02114 USA. [Litvan, I.] Univ Calif San Diego, Dept Neurosci, Movement Disorder Ctr, San Diego, CA 92103 USA. [Tartaglia, M. C.] Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P335 BP 371 EP 371 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400386 ER PT J AU Boxer, A Rosen, H Boeve, B Heuer, H Laxineta, S Grossman, M Coppola, G Dickerson, B Bordelon, Y Conwit, R Dheel, C Faber, K Feldman, H Ferguson, J Fields, J Fong, J Foroud, T Galpern, W Ghoshal, N Graff-Radford, N Hsiung, R Huey, E Irwin, D Kantarci, K Kaufer, D Karydas, A Klein, A Knopman, D Kornak, J Kramer, J Kukull, W Litvan, I Mackenzie, I Mendez, M Miller, B Miller, M Onyike, C Pantelyat, A Rademakers, R Roberson, E Sutherland, M Tartaglia, MC Tatton, N Toga, A Vetor, A Weintraub, S Wszolek, Z AF Boxer, A. Rosen, H. Boeve, B. Heuer, H. Laxineta, S. Grossman, M. Coppola, G. Dickerson, B. Bordelon, Y. Conwit, R. Dheel, C. Faber, K. Feldman, H. Ferguson, J. Fields, J. Fong, J. Foroud, T. Galpern, W. Ghoshal, N. Graff-Radford, N. Hsiung, R. Huey, E. Irwin, D. Kantarci, K. Kaufer, D. Karydas, A. Klein, A. Knopman, D. Kornak, J. Kramer, J. Kukull, W. Litvan, I. Mackenzie, I. Mendez, M. Miller, B. Miller, M. Onyike, C. Pantelyat, A. Rademakers, R. Roberson, E. Sutherland, M. Tartaglia, M. C. Tatton, N. Toga, A. Vetor, A. Weintraub, S. Wszolek, Z. TI Characteristics and progress on the Initial 256 participants in the advancing research and treatment in frontotemporal lobar degeneration (ARTFL) North American Rare disease clinical research consortium SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Boxer, A.; Rosen, H.; Heuer, H.; Laxineta, S.; Fong, J.; Karydas, A.; Kornak, J.; Kramer, J.; Miller, B.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Boeve, B.; Dheel, C.; Fields, J.; Kantarci, K.; Knopman, D.; Miller, M.] Mayo Clin, Rochester, MN USA. [Grossman, M.; Irwin, D.] Univ Penn, Philadelphia, PA 19104 USA. [Coppola, G.; Bordelon, Y.; Mendez, M.] Univ Calif Los Angeles, Los Angeles, CA USA. [Dickerson, B.] Massachusetts Gen Hosp, Cambridge, MA USA. [Conwit, R.; Ferguson, J.; Sutherland, M.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Faber, K.; Foroud, T.; Vetor, A.] NCRAD, Indianapolis, IN USA. [Feldman, H.; Hsiung, R.; Mackenzie, I.] Univ British Columbia, Vancouver, BC, Canada. [Galpern, W.] Janssen Pharmaceut, Washington, DC USA. [Ghoshal, N.] Washington Univ, St Louis, MO USA. [Graff-Radford, N.; Rademakers, R.; Roberson, E.; Wszolek, Z.] Mayo Clin, Jacksonville, FL 32224 USA. [Huey, E.] Columbia Univ, New York, NY USA. [Kaufer, D.] Univ N Carolina, Chapel Hill, NC USA. [Klein, A.] CurePSP, New York, NY USA. [Kukull, W.] Univ Washington, Seattle, WA 98195 USA. [Litvan, I.] Univ Calif San Diego, San Diego, CA 92103 USA. [Mendez, M.; Onyike, C.; Pantelyat, A.] Johns Hopkins Univ, Baltimore, MD USA. [Roberson, E.] Univ Alabama Birmingham, Birmingham, AL USA. [Tartaglia, M. C.] Univ Toronto, Toronto, ON, Canada. [Tatton, N.] AFTD, Radnor, PA USA. [Toga, A.] Univ Southern Calif, Los Angeles, CA USA. [Weintraub, S.] Northwestern Univ, Chicago, IL 60611 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 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P352 BP 379 EP 379 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400403 ER PT J AU Rosen, H Knopman, D Dickerson, B Boeve, B Urbano, M Caplan, A Laxineta, S Miller, B AF Rosen, H. Knopman, D. Dickerson, B. Boeve, B. Urbano, M. Caplan, A. Laxineta, S. Miller, B. TI Results from the frontotemporal lobar degeneration neuroimaging initiative (FTLDNI) SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Rosen, H.; Urbano, M.; Caplan, A.; Laxineta, S.; Miller, B.] Univ Calif San Francisco, Neurol, San Francisco, CA USA. [Knopman, D.; Boeve, B.] Mayo Clin, Rochester, MN USA. [Dickerson, B.] Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P393 BP 396 EP 396 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400444 ER PT J AU Castrillon, G Velilla, L Giraldo, M Zapata, A Bustamante, C Lopera, F Quiroz, Y AF Castrillon, G. Velilla, L. Giraldo, M. Zapata, A. Bustamante, C. Lopera, F. Quiroz, Y. TI Functional connectivity differences between behavioral-variant frontotemporal dementia and early-onset Alzheimer's disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 10th International Conference on Frontotemporal Dementias CY AUG 31-SEP 02, 2016 CL Munich, GERMANY C1 [Castrillon, G.; Bustamante, C.] Inst Alta Tecnol Med, Medellin, Colombia. [Castrillon, G.] TUM NIC, Techn Univ Munich, Munich, Colombia. [Velilla, L.; Giraldo, M.; Zapata, A.; Lopera, F.; Quiroz, Y.] Grp Neuroci Antioquia, Medellin, Colombia. [Quiroz, Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2016 VL 138 SU 1 SI SI MA P424 BP 407 EP 407 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DU9WI UT WOS:000382568400475 ER PT J AU Chandra, RV Chan, NC Leslie-Mazwi, TM Mehta, BP Hirsch, JA AF Chandra, Ronil V. Chan, Noel C. Leslie-Mazwi, Thabele M. Mehta, Brijesh P. Hirsch, Joshua A. TI Platelet function testing: does a randomized controlled trial settle the debate? SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Editorial Material DE Aneurysm; Platelets ID NEUROINTERVENTIONAL PROCEDURES; THERAPY; PRASUGREL; STANDARD C1 [Chandra, Ronil V.] Monash Hlth, Monash Imaging, Intervent Neuroradiol Unit, 246 Clayton Rd, Melbourne, Vic 3168, Australia. [Chandra, Ronil V.; Chan, Noel C.] Monash Univ, Dept Med, Melbourne, Vic, Australia. [Chan, Noel C.] Monash Hlth, Dept Haematol, Melbourne, Vic, Australia. [Leslie-Mazwi, Thabele M.; Hirsch, Joshua A.] Harvard Med Sch, Massachusetts Gen Hosp, NeuroEndovasc Program, Boston, MA USA. [Mehta, Brijesh P.] Mem Neurosci Inst, Hollywood, FL USA. RP Chandra, RV (reprint author), Monash Hlth, Monash Imaging, Intervent Neuroradiol Unit, 246 Clayton Rd, Melbourne, Vic 3168, Australia. EM ronil.chandra@monashhealth.org NR 11 TC 0 Z9 0 U1 1 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 EI 1759-8486 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD AUG PY 2016 VL 8 IS 8 BP 768 EP 769 DI 10.1136/neurintsurg-2015-011954 PG 2 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA DU3YO UT WOS:000382148800007 PM 26206806 ER PT J AU Hirsch, JA Leslie-Mazwi, TM Patel, AB Rabinov, JD Gonzalez, RG Barr, RM Nicola, GN Klucznik, RP Prestigiacomo, CJ Manchikanti, L AF Hirsch, Joshua A. Leslie-Mazwi, Thabele M. Patel, Aman B. Rabinov, James D. Gonzalez, Ramon G. Barr, Robert M. Nicola, Gregory N. Klucznik, Richard P. Prestigiacomo, Charles J. Manchikanti, Laxmaiah TI MACRA: background, opportunities and challenges for the neurointerventional specialist SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Review DE Political; Economics ID SUSTAINABLE GROWTH-RATE; INTERVENTIONAL PAIN MANAGEMENT; RELATIVE-VALUE; STICK POLICY; RATE FORMULA; CARE; REPEAL; CARROT; PRIMER AB The legislative branch of government took many by surprise when it announced the Medicare Access and CHIP Reauthorization Act of 2015. Once the Act was passed, President Obama quickly signed this bipartisan, bicameral effort into law. A foundational element of this legislation was the permanent repeal of the sustainable growth rate formula. Physicians and their patients were appropriately enthusiastic about this development. The Medicare Access and CHIP Reauthorization Act of 2015 included additional elements of considerable interest to neurointerventional specialists. C1 [Hirsch, Joshua A.; Leslie-Mazwi, Thabele M.; Patel, Aman B.; Rabinov, James D.] Harvard Med Sch, Massachusetts Gen Hosp, NeuroEndovasc Program, Boston, MA 02114 USA. [Gonzalez, Ramon G.] Harvard Med Sch, Massachusetts Gen Hosp, Neuroradiol Div, Boston, MA USA. [Barr, Robert M.] Mecklenburg Radiol Associates PA, Charlotte, NC USA. [Nicola, Gregory N.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Klucznik, Richard P.] Cornell Univ, Weill Med Coll, Houston Methodist Neurol Inst, Houston, TX USA. [Prestigiacomo, Charles J.] Rutgers New Jersey Med Sch, Dept Neurol Surg, Newark, NJ USA. [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Dept Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. RP Hirsch, JA (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, NeuroEndovasc Program, Boston, MA 02114 USA. EM Hirsch@snisonline.org NR 26 TC 9 Z9 9 U1 1 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 EI 1759-8486 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD AUG PY 2016 VL 8 IS 8 BP 868 EP 874 DI 10.1136/neurintsurg-2015-011952 PG 7 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA DU3YO UT WOS:000382148800027 PM 26220409 ER PT J AU Jinno, S Hasegawa, K Neogi, T Goto, T Dubreuil, M AF Jinno, Sadao Hasegawa, Kohei Neogi, Tuhina Goto, Tadahiro Dubreuil, Maureen TI Trends in Emergency Department Visits and Charges for Gout in the United States between 2006 and 2012 SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE GOUT; EPIDEMIOLOGY; OUTCOME ASSESSMENT ID HEALTH; CARE; FREQUENCY AB Objective. To examine temporal trends in the rate of gout emergency department (ED) visits and charges in the United States between 2006 and 2012. Methods. A serial cross-sectional analysis of the Nationwide Emergency Department Sample. Results. The rate of ED visits for gout in adults overall increased from 75.0 to 85.4 per 100,000 persons over the study period (14% increase, p < 0.001), and increased 29% for those aged 45-54 years. Nationwide ED charges increased from $156 million to $281 million (80% increase, p < 0.001). Conclusion. Between 2006 and 2012, the rate of gout ED visits increased among US adults, most notably in those aged 45-54 years. C1 [Jinno, Sadao; Neogi, Tuhina; Dubreuil, Maureen] Boston Univ, Sch Med, Dept Med, Rheumatol Sect, Boston, MA 02118 USA. [Hasegawa, Kohei] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Neogi, Tuhina] Boston Univ, Sch Med, Dept Med, Sect Clin Epidemiol Res & Training Unit, Boston, MA 02118 USA. [Goto, Tadahiro; Dubreuil, Maureen] VA Boston Healthcare Syst, Boston, MA USA. RP Jinno, S (reprint author), Boston Univ, Sch Med, Dept Med, Rheumatol Sect, Boston, MA 02118 USA. EM Sadao.jinno@bmc.org FU NIAMS NIH HHS [P60 AR047785] NR 15 TC 3 Z9 3 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD AUG PY 2016 VL 43 IS 8 BP 1589 EP 1592 DI 10.3899/jrheum.151432 PG 4 WC Rheumatology SC Rheumatology GA DS6HG UT WOS:000380882300022 PM 27252429 ER PT J AU Spence, RT Zargaran, E Hameed, SM Navsaria, P Nicol, A AF Spence, Richard Trafford Zargaran, Eiman Hameed, S. Morad Navsaria, Pradeep Nicol, Andrew TI Mobile health technology transforms injury severity scoring in South Africa SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Injury severity scoring; mHealth technology; Quality improvement ID KAMPALA TRAUMA SCORE; QUALITY IMPROVEMENT PROGRAM; IN-HOSPITAL MORTALITY; LOW-RESOURCE SETTINGS; DATA-BANK ITDB; TRISS METHOD; CARE; SURVEILLANCE; SCALE; EXPERIENCE AB Background: The burden of data collection associated with injury severity scoring has limited its application in areas of the world with the highest incidence of trauma. Material and Methods: Since January 2014, electronic records (electronic Trauma Health Records [eTHRs]) replaced all handwritten records at the Groote Schuur Hospital Trauma Unit in South Africa. Data fields required for Glasgow Coma Scale, Revised Trauma Score, Kampala Trauma Score, Injury Severity Score (ISS), and Trauma Score-Injury Severity Score calculations are now prospectively collected. Fifteen months after implementation of eTHR, the injury severity scores were compared as predictors of mortality on three accounts: (1) ability to discriminate (area under receiver operating curve, ROC); (2) ability to calibrate (observed versus expected ratio, O/E); and (3) feasibility of data collection (rate of missing data). Results: A total of 7460 admissions were recorded by eTHR from April 1, 2014 to July 7, 2015, including 770 severely injured patients (ISS > 15) and 950 operations. The mean age was 33.3 y (range 13-94), 77.6% were male, and the mechanism of injury was penetrating in 39.3% of cases. The cohort experienced a mortality rate of 2.5%. Patient reserve predictors required by the scores were 98.7% complete, physiological injury predictors were 95.1% complete, and anatomic injury predictors were 86.9% complete. The discrimination and calibration of Trauma Score-Injury Severity Score was superior for all admissions (ROC 0.9591 and O/E 1.01) and operatively managed patients (ROC 0.8427 and O/E 0.79). In the severely injured cohort, the discriminatory ability of Revised Trauma Score was superior (ROC 0.8315), but no score provided adequate calibration. Conclusions: Emerging mobile health technology enables reliable and sustainable injury severity scoring in a high-volume trauma center in South Africa. (C) 2016 Elsevier Inc. All rights reserved. C1 [Spence, Richard Trafford] Massachusetts Gen Hosp, Codman Ctr, Dept Surg, Boston, MA 02114 USA. [Spence, Richard Trafford; Hameed, S. Morad; Navsaria, Pradeep; Nicol, Andrew] Univ Cape Town, Groote Schuur Hosp, Ctr Trauma, Dept Gen Surg, Cape Town, South Africa. [Zargaran, Eiman] Univ British Columbia, Dept Surg, Vancouver, BC, Canada. [Spence, Richard Trafford] Groote Schuur Hosp, Dept Gen Surg, Main Rd, ZA-7935 Cape Town, South Africa. RP Spence, RT (reprint author), Codman Ctr Clin Effectiveness Surg, Charles River Plaza,Suite 403,165 Cambridge St, Boston, MA 02114 USA. EM Spnric004@myuct.ac.za NR 36 TC 1 Z9 1 U1 2 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 EI 1095-8673 J9 J SURG RES JI J. Surg. Res. PD AUG PY 2016 VL 204 IS 2 BP 384 EP 392 DI 10.1016/j.jss.2016.05.021 PG 9 WC Surgery SC Surgery GA DU5CP UT WOS:000382230100015 PM 27565074 ER PT J AU Varley, PR Feske, U Gao, S Stone, RA Zhang, SJ Monte, R Arnold, RM Hall, DE AF Varley, Patrick R. Feske, Ulrike Gao, Shasha Stone, Roslyn A. Zhang, Sijian Monte, Robert Arnold, Robert M. Hall, Daniel E. TI Time required to review research protocols at 10 Veterans Affairs Institutional Review Boards SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Quality improvement; Ethics committee; Efficiency ID CLINICAL-RESEARCH; QUALITY; MULTICENTER; OVERSIGHT; EVENTS; REFORM; COSTS AB Background: Despite perceptions that institutional review boards ( IRBs) delay research, little is known about how long it takes to secure IRB approval. We retrospectively quantified IRB review times at 10 large Veterans Affairs (VA) IRBs. Methods: We collected IRB records pertaining to a stratified random sample of research protocols drawn from 10 of the 26 largest VA IRBs. Two independent analysts abstracted dates from the IRB records, from which we calculated overall and incremental review times. We used multivariable linear regression to assess variation in total and incremental review times by IRB and review level (i.e., exempt, expedited, or full board) and to identify potential targets for efforts to improve the efficiency and uniformity of the IRB review process. Results: In a sample of 277 protocols, the mean review time was 112 d (95% confidence interval [CI]: 105-120). Compared with full-board reviews at IRB 1, average review times at IRBs 3, 8, 9, and 10 were 27 (95% CI: 6-48), 37 (95% CI: 11-63), 45 (95% CI: 20-69), and 24 (95% CI: 2-45) d shorter, and at IRB 6, times were 56 (95% CI: 28-84) d longer. Across all IRBs, expedited reviews were 44 (95% CI: 30-58) d shorter on average than were full-board reviews, with no significant difference between exempt and full-board reviews. However, after subtracting the time required for Research and Development Committee review, exempt reviews were 21 (95% CI: 1-41) d shorter on average than were full-board reviews. Conclusions: IRB review times differ significantly by IRB and review level. Few VA IRBs approach a consensus panel goal of 60 d for IRB review. The unexpectedly longer review times for exempt protocols in the VA can be attributed to time required for Research and Development Committee review. Prospective, routine collection of key time points in the IRB review process could inform IRB-specific initiatives for reducing VA IRB review times. Published by Elsevier Inc. C1 [Varley, Patrick R.; Hall, Daniel E.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Feske, Ulrike; Gao, Shasha; Stone, Roslyn A.; Zhang, Sijian; Hall, Daniel E.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Bldg 30,Univ Dr,151C, Pittsburgh, PA 15240 USA. [Monte, Robert] VA Pittsburgh Healthcare Syst, Vet Engn Resource Ctr, Pittsburgh, PA USA. [Arnold, Robert M.] Univ Pittsburgh, Dept Gen Internal Med, Pittsburgh, PA USA. RP Hall, DE (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Bldg 30,Univ Dr,151C, Pittsburgh, PA 15240 USA. EM hallde@upmc.edu FU U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development [CDA 08-281, SDR 11-399-1] FX This research was supported by supported by the U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development (CDA 08-281 and SDR 11-399-1). We are grateful to Laura Lupovitz for her careful coding of IRB review times, the staff of the VA Pittsburgh Veterans Engineering Resource Center for their assistance with process flow mapping, and for the participation and support of the IRB staff at each of the participating institutions. Weare also grateful to Michael Fine, Bruce Ling, Charles Lidz, Galen Switzer, Susan Zickmund, Barbara Hanusa and Aram Dobalian who were involved in other parts of this research and served throughout as advisors to our team. NR 25 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 EI 1095-8673 J9 J SURG RES JI J. Surg. Res. PD AUG PY 2016 VL 204 IS 2 BP 481 EP 489 DI 10.1016/j.jss.2016.06.004 PG 9 WC Surgery SC Surgery GA DU5CP UT WOS:000382230100027 PM 27565086 ER PT J AU Fearing, CM Melton, DW Lei, XF Hancock, H Wang, HZ Sarwar, ZU Porter, L McHale, M McManus, LM Shireman, PK AF Fearing, Caitlin M. Melton, David W. Lei, Xiufen Hancock, Heather Wang, Hanzhou Sarwar, Zaheer U. Porter, Laurel McHale, Matthew McManus, Linda M. Shireman, Paula K. TI Increased Adipocyte Area in Injured Muscle With Aging and Impaired Remodeling in Female Mice SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Sarcopenia; Muscle regeneration; Monocyte; macrophage ID CONTRACTION-INDUCED INJURY; MOUSE SKELETAL-MUSCLE; AGE-RELATED-CHANGES; SATELLITE CELLS; MALE RATS; FIBRO/ADIPOGENIC PROGENITORS; MACROPHAGE PHENOTYPE; STEM-CELLS; OLD RATS; REGENERATION AB We demonstrated that young male and female mice similarly regenerated injured skeletal muscle; however, female mice transiently increased adipocyte area within regenerated muscle in a sex hormone-dependent manner. We extended these observations to investigate the effect of aging and sex on sarcopenia and muscle regeneration. Cardiotoxin injury to the tibialis anterior muscle of young, middle, and old-aged C57Bl/6J male and female mice was used to measure regenerated myofiber cross-sectional area (CSA), adipocyte area, residual necrosis, and inflammatory cell recruitment. Baseline (uninjured) myofiber CSA was decreased in old mice of both sexes compared to young and middle-aged mice. Regenerated CSA was similar in male mice in all age groups until baseline CSA was attained but decreased in middle and old age female mice compared to young females. Furthermore, adipocyte area within regenerated muscle was transiently increased in young females compared to young males and these sex-dependent increases persisted in middle and old age female mice and were associated with increased Pparg. Young female mice had more pro-inflammatory monocytes/macrophages in regenerating muscle than young male mice and increased Sca-1(+)CD45(-)cells. In conclusion, sex and age influence pro-inflammatory cell recruitment, muscle regeneration, and adipocyte area following skeletal muscle injury. C1 [Fearing, Caitlin M.; Melton, David W.; Lei, Xiufen; Hancock, Heather; Wang, Hanzhou; Sarwar, Zaheer U.; Porter, Laurel; McHale, Matthew; Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, San Antonio, TX 78229 USA. [Melton, David W.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Melton, David W.; McManus, Linda M.; Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [McManus, Linda M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [McManus, Linda M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Periodont, San Antonio, TX 78229 USA. [Shireman, Paula K.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Shireman, PK (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, Div Vasc & Endovasc Surg, 7703 Floyd Curl Dr MSC 7741, San Antonio, TX 78229 USA. EM shireman@uthscsa.edu FU National Institutes of Health [HL074236, HL110743, CA054174]; Nathan Shock Centers of Excellence in Basic Biology of Aging [AG013319]; Veterans Administration Merit Review [1I01BX001186]; University of Texas Health Science Center, San Antonio; CTSA grant [UL1 TR001120] FX These studies were supported, in part, by grants from the National Institutes of Health (HL074236, HL110743), Nathan Shock Centers of Excellence in Basic Biology of Aging (AG013319), and the Veterans Administration Merit Review (1I01BX001186). Data were generated in the Flow Cytometry Facility, which was supported by the University of Texas Health Science Center, San Antonio and a grant from the National Institutes of Health (CA054174) to the Cancer Therapy & Research Center and UL1 TR001120 (CTSA grant). NR 71 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 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD AUG PY 2016 VL 71 IS 8 BP 992 EP 1004 DI 10.1093/gerona/glv104 PG 13 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA DV9BX UT WOS:000383235400002 PM 26273023 ER PT J AU Yaffe, K Peltz, CB Ewing, SK McCulloch, CE Cummings, SR Cauley, JA Hillier, TA Ensrud, KE AF Yaffe, Kristine Peltz, Carrie B. Ewing, Susan K. McCulloch, Charles E. Cummings, Steve R. Cauley, Jane A. Hillier, Teresa A. Ensrud, Kristine E. TI Long-term Cognitive Trajectories and Mortality in Older Women SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Cognitive trajectories; Global cognition; Executive function; All-cause mortality; Cardiovascular mortality; Oldest old ID ALZHEIMERS-DISEASE; EXECUTIVE FUNCTION; COMMUNITY SAMPLE; RISK-FACTORS; ASSOCIATION; DECLINE; SURVIVAL; DEMENTIA; HEALTH; LIFE AB Few studies have examined whether change in cognition is linked to mortality. This study examined the relationship between cognitive trajectories in older age and risk of death. We studied community-dwelling, nondemented women aged 65+ (mean age = 71) enrolled in a prospective study of aging and followed up to 25 years. A modified Mini-Mental State Examination (mMMSE) and Trail Making Task Part B (TMTB) were administered at multiple visits during follow-up. We examined the association between cognitive trajectories (analyzed by quintiles) from baseline to age 80 (n = 7,477 for mMMSE and n = 6,503 for TMTB) and all-cause mortality after age 80 using Cox regression models, both unadjusted and adjusted for education, physical activity, alcohol, depression score, current smoking and history of hypertension and diabetes. Cause of death was determined from death certificates, classified as cardiovascular, cancer and other. Women with greater rate of decline were older, less educated, less physically active, had higher depression score and were more likely to have a history of hypertension and diabetes (all p < .01). Participants with the greatest decline (quintile 1) had an increased risk of death (mMMSE hazard ratio [HR] = 1.28; TMTB HR = 1.43] and those with the least decline (quintile 5) had a decreased risk of death (mMMSE HR = 0.73; TMTB HR = 0.61) compared with intermediate decliners (quintiles 2-4). Cognitive trajectories were associated with cardiovascular mortality and other causes of death, but not cancer deaths. Our study suggests that greater decline in general cognition or executive function is associated with higher rates of mortality in oldest-old women. C1 [Yaffe, Kristine; Ewing, Susan K.; McCulloch, Charles E.; Cummings, Steve R.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine; Ewing, Susan K.; McCulloch, Charles E.; Cummings, Steve R.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Yaffe, Kristine; Ewing, Susan K.; McCulloch, Charles E.; Cummings, Steve R.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Yaffe, Kristine; Peltz, Carrie B.] San Francisco VA Med Ctr, Dept Mental Hlth, San Francisco, CA USA. [Peltz, Carrie B.] NCIRE Vet Hlth Res Inst, San Francisco, CA USA. [Cauley, Jane A.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Hillier, Teresa A.] Kaiser Permanente Ctr Hlth Res Northwest Hawaii, Portland, OR USA. [Ensrud, Kristine E.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. [Ensrud, Kristine E.] Minneapolis VA Hlth Care Syst, Dept Med, Minneapolis, MN USA. RP Peltz, CB (reprint author), 4150 Clement St 116H, San Francisco, CA 94121 USA. EM carrie.peltz2@va.gov OI Cauley, Jane A/0000-0003-0752-4408 FU National Institutes of Health; National Institute on Aging [R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, R01 AG027576] FX The Study of Osteoporotic Fractures is supported by National Institutes of Health funding. The National Institute on Aging provides support under the following grant numbers: R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, and R01 AG027576. NR 40 TC 0 Z9 0 U1 4 U2 5 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 AUG PY 2016 VL 71 IS 8 BP 1074 EP 1080 DI 10.1093/gerona/glw003 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA DV9BX UT WOS:000383235400012 PM 26843186 ER PT J AU Mischoulon, D Zajecka, J Freeman, MP Fava, M AF Mischoulon, David Zajecka, John Freeman, Marlene P. Fava, Maurizio TI Does folic acid interfere with lamotrigine? SO LANCET PSYCHIATRY LA English DT Letter ID DEPRESSION; METAANALYSIS; PLACEBO; TRIALS C1 [Mischoulon, David; Freeman, Marlene P.; Fava, Maurizio] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Zajecka, John] Rush Univ, Med Ctr, Womans Board Depress Treatment Res Ctr, Chicago, IL 60612 USA. RP Mischoulon, D (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM dmischoulon@partners.org FU AstraZeneca; Avanir Pharmaceuticals; Cerecor; Eli Lilly and Company; EnVivo Pharmaceuticals; Euthymics Bioscience; Forest Pharmaceuticals; FORUM Pharmaceuticals; Janssen RD; Johnson & Johnson Pharmaceutical Research Development; Lundbeck; Methylation Sciences; National Center for Complementary and Alternative Medicine (NCCAM); National Coordinating Center for Integrative Medicine (NiiCM); National Institute of Drug Abuse (NIDA); National Institute of Mental Health (NIMH); Neuralstem; Novartis AG; PamLab; Pfizer; PharmoRx Therapeutics; Photothera; Reckitt Benckiser; Roche Pharmaceuticals; RCT Logic; Stanley Medical Research Institute (SMRI), Takeda; Tal Medical FX DM reports non-financial support from PamLab; research support from PharmoRx, Fisher Wallace; and received eicosapentaenoic acid (EPA) for study from Nordic Naturals, outside the submitted work. JZ reports grants from Actavis, Alkermes, Allergan, AstraZeneca, Axsome, Cyberonics, EIMindA, Cheryl T Herman Foundation, Hoffman-La Roche, Janssen, Neuralstem, Otsuka, National Institutes of Health, Abbvie, Avanir, Eli Lilly, and Pamlab/Nestle; and grants and personal fees from Forest, Naurex, Shire, and Takeda; personal fees from Abbvie, Avanir, and Eli Lilly, outside the submitted work. MPF reports grants and is on the advisory board of Takeda, grants from JayMac Pharmaceuticals, is on the advisory board of JDS therapeutics, Sunovion, and Sage; does medical editing for DSM nutritionals and the GOED newsletter; and is on the independent data safety monitoring committee of Johnson & Johnson Janssen, outside the submitted work. MF reports receiving research medications from Pamlab; grants for research support from AstraZeneca, Avanir Pharmaceuticals, Cerecor, Eli Lilly and Company, EnVivo Pharmaceuticals, Euthymics Bioscience, Forest Pharmaceuticals, FORUM Pharmaceuticals, Janssen R&D, Johnson & Johnson Pharmaceutical Research & Development, Lundbeck, Methylation Sciences, National Center for Complementary and Alternative Medicine (NCCAM), National Coordinating Center for Integrative Medicine (NiiCM), National Institute of Drug Abuse (NIDA), National Institute of Mental Health (NIMH), Neuralstem, Novartis AG, PamLab, Pfizer, PharmoRx Therapeutics, Photothera, Reckitt Benckiser, Roche Pharmaceuticals, RCT Logic (formerly Clinical Trials Solutions), Stanley Medical Research Institute (SMRI), Takeda, Tal Medical; advisory board or consultant work from Acadia, Alkermes, AstraZeneca, Auspex, Avanir Pharmaceuticals, AXSOME Therapeutics, Biogen, Bristol-Myers Squibb, Cerecor, Dinippon Sumitomo Pharma Co, Eli Lilly and Company, Euthymics Bioscience, Forest Pharmaceuticals, FORUM Pharmaceuticals, GenOmind, GlaxoSmithKline, Intracellular, Janssen Pharmaceutica, Johnson & Johnson Pharmaceutical Research & Development, LLC, Lundbeck, Merck & Co, MSI Methylation Sciences, Naurex, Nestle Health Sciences, Neuralstem, Novartis AG, Nutrition 21, Osmotica, Otsuka Pharmaceuticals, Pamlab, Pfizer, PharmoRx Therapeutics, PPD, Puretech Ventures, PsychoGenics, RCT Logic (formerly Clinical Trials Solutions), Ridge Diagnostics, Roche, Sanofi-Aventis US, Servier Laboratories, Sunovion Pharmaceuticals, Taisho Pharmaceutical, Takeda Pharmaceutical, Tal Medical, VistaGenl; and personal fees from speaking and publishing from American Society of Clinical Psychopharmacology, Belvoir Media Group, CME Institute/Physicians Postgraduate Press, MGH Psychiatry Academy; and equity holdings from Compellis and PsyBrain outside the submitted work. DM wrote the first draft of the letter and discussed relevant clinical trials of folate augmentation. JZ and MF provided discussion about mechanisms of action, and relevant references. MPF provided discussion about the impact of folic acid in pregnancy and neural tube defects, and relevant references. All authors have approved this submitted version. NR 5 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 2215-0374 J9 LANCET PSYCHIAT JI Lancet Psychiatry PD AUG PY 2016 VL 3 IS 8 BP 704 EP 705 PG 2 WC Psychiatry SC Psychiatry GA DU5TU UT WOS:000382276500009 PM 27475760 ER PT J AU Netea, MG Joosten, LAB Li, Y Kumar, V Oosting, M Smeekens, S Jaeger, M ter Horst, R Schirmer, M Vlamakis, H Notebaart, R Pavelka, N Aguirre-Gamboa, RR Swertz, MA Tunjungputri, RN van de Heijden, W Franzosa, EA Ng, A Graham, D Lassen, K Schraa, K Netea-Maier, R Smit, J de Mast, Q van de Veerdonk, F Kullberg, BJ Tack, C van de Munckhof, I Rutten, J van der Graaf, J Franke, L Hofker, M Jonkers, I Platteel, M Maatman, A Fu, JY Zhernakova, A van der Meer, JWM Dinarello, CA van der Ven, A Huttenhouwer, C Koenen, H Joosten, I Xavier, RJ Wijmenga, C AF Netea, Mihai G. Joosten, Leo A. B. Li, Yang Kumar, Vinod Oosting, Marije Smeekens, Sanne Jaeger, Martin ter Horst, Rob Schirmer, Melanie Vlamakis, Hera Notebaart, Richard Pavelka, Norman Aguirre-Gamboa, Raul Raul Swertz, Morris A. Tunjungputri, Rahajeng N. van de Heijden, Wouter Franzosa, Eric A. Ng, Aylwin Graham, Daniel Lassen, Kara Schraa, Kiki Netea-Maier, Romana Smit, Jan de Mast, Quirijn van de Veerdonk, Frank Kullberg, Bart Jan Tack, Cees van de Munckhof, Inge Rutten, Joost van der Graaf, Jacqueline Franke, Lude Hofker, Marten Jonkers, Iris Platteel, Mathieu Maatman, Astrid Fu, Jingyuan Zhernakova, Alexandra van der Meer, Jos W. M. Dinarello, Charles A. van der Ven, Andre Huttenhouwer, Curtis Koenen, Hans Joosten, Irma Xavier, Ramnik J. Wijmenga, Cisca TI Understanding human immune function using the resources from the Human Functional Genomics Project SO NATURE MEDICINE LA English DT Letter C1 [Netea, Mihai G.; Joosten, Leo A. B.; Oosting, Marije; Smeekens, Sanne; Jaeger, Martin; ter Horst, Rob; Notebaart, Richard; Pavelka, Norman; Tunjungputri, Rahajeng N.; van de Heijden, Wouter; Schraa, Kiki; Netea-Maier, Romana; Smit, Jan; de Mast, Quirijn; van de Veerdonk, Frank; Kullberg, Bart Jan; Tack, Cees; van de Munckhof, Inge; Rutten, Joost; van der Graaf, Jacqueline; van der Meer, Jos W. M.; Dinarello, Charles A.; van der Ven, Andre] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Nijmegen, Netherlands. [Netea, Mihai G.; Joosten, Leo A. B.; Oosting, Marije; Smeekens, Sanne; Jaeger, Martin; ter Horst, Rob; Notebaart, Richard; Pavelka, Norman; Tunjungputri, Rahajeng N.; van de Heijden, Wouter; Schraa, Kiki; Netea-Maier, Romana; Smit, Jan; de Mast, Quirijn; van de Veerdonk, Frank; Kullberg, Bart Jan; Tack, Cees; van de Munckhof, Inge; Rutten, Joost; van der Graaf, Jacqueline; van der Meer, Jos W. M.; Dinarello, Charles A.; van der Ven, Andre] Radboud Univ Nijmegen, Med Ctr, Radboud Ctr Infect Dis, Nijmegen, Netherlands. [Li, Yang; Kumar, Vinod; Aguirre-Gamboa, Raul Raul; Swertz, Morris A.; Franke, Lude; Hofker, Marten; Jonkers, Iris; Platteel, Mathieu; Maatman, Astrid; Fu, Jingyuan; Zhernakova, Alexandra; Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. [Schirmer, Melanie; Vlamakis, Hera; Franzosa, Eric A.; Ng, Aylwin; Graham, Daniel; Lassen, Kara; Huttenhouwer, Curtis; Xavier, Ramnik J.] Harvard Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA USA. [Schirmer, Melanie; Vlamakis, Hera; Franzosa, Eric A.; Ng, Aylwin; Graham, Daniel; Lassen, Kara; Huttenhouwer, Curtis; Xavier, Ramnik J.] Harvard Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA USA. [Schirmer, Melanie; Vlamakis, Hera; Franzosa, Eric A.; Ng, Aylwin; Graham, Daniel; Lassen, Kara; Huttenhouwer, Curtis; Xavier, Ramnik J.] Broad Inst MIT & Harvard Univ, Cambridge, MA USA. [Pavelka, Norman] ASTAR, Singapore Immunol Network SIgN, Singapore, Singapore. [Dinarello, Charles A.] Univ Colorado, Dept Infect Dis, Denver, CO 80202 USA. [Koenen, Hans; Joosten, Irma] Radboud Univ Nijmegen, Med Ctr, Dept Lab Med, Lab Med Immunol, Nijmegen, Netherlands. RP Netea, MG (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Nijmegen, Netherlands.; Netea, MG (reprint author), Radboud Univ Nijmegen, Med Ctr, Radboud Ctr Infect Dis, Nijmegen, Netherlands. EM mihai.netea@radboudumc.nl RI Smeekens, Sanne/G-8307-2011; Oosting, Marije/H-7437-2015; Franke, Lude/P-7036-2016; Wijmenga, Cisca/D-2173-2009; OI Smeekens, Sanne/0000-0002-7835-914X; Franke, Lude/0000-0002-5159-8802; Pavelka, Norman/0000-0003-4542-9970 NR 10 TC 1 Z9 1 U1 3 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD AUG PY 2016 VL 22 IS 8 BP 831 EP 833 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA DS7YV UT WOS:000381000200005 PM 27490433 ER PT J AU Deeks, SG Lewin, SR Ross, AL Ananworanich, J Benkirane, M Cannon, P Chomont, N Douek, D Lifson, JD Lo, YR Kuritzkes, D Margolis, D Mellors, J Persaud, D Tucker, JD Barre-Sinoussi, F Alter, G Auerbach, J Autran, B Barouch, DH Behrens, G Cavazzana, M Chen, ZW Cohen, EA Corbelli, GM Eholie, S Eyal, N Fidler, S Garcia, L Grossman, C Henderson, G Henrich, TJ Jefferys, R Kiem, HP McCune, J Moodley, K Newman, PA Nijhuis, M Nsubuga, MS Ott, M Palmer, S Richman, D Saez-Cirion, A Sharp, M Siliciano, J Silvestri, G Singh, J Spire, B Taylor, J Tolstrup, M Valente, S van Lunzen, J Walensky, R Wilson, I Zack, J AF Deeks, Steven G. Lewin, Sharon R. Ross, Anna Laura Ananworanich, Jintanat Benkirane, Monsef Cannon, Paula Chomont, Nicolas Douek, Daniel Lifson, Jeffrey D. Lo, Ying-Ru Kuritzkes, Daniel Margolis, David Mellors, John Persaud, Deborah Tucker, Joseph D. Barre-Sinoussi, Francoise Alter, Galit Auerbach, Judith Autran, Brigitte Barouch, Dan H. Behrens, Georg Cavazzana, Marina Chen, Zhiwei Cohen, Eric A. Corbelli, Giulio Maria Eholie, Serge Eyal, Nir Fidler, Sarah Garcia, Laurindo Grossman, Cynthia Henderson, Gail Henrich, Timothy J. Jefferys, Richard Kiem, Hans-Peter McCune, Joseph Moodley, Keymanthri Newman, Peter A. Nijhuis, Monique Nsubuga, Moses Supercharger Ott, Melanie Palmer, Sarah Richman, Douglas Saez-Cirion, Asier Sharp, Matthew Siliciano, Janet Silvestri, Guido Singh, Jerome Spire, Bruno Taylor, Jeffrey Tolstrup, Martin Valente, Susana van Lunzen, Jan Walensky, Rochelle Wilson, Ira Zack, Jerome CA Int AIDS Soc Cure Working Grp TI International AIDS Society global scientific strategy: towards an HIV cure 2016 SO NATURE MEDICINE LA English DT Article ID CD4(+) T-CELLS; SUPPRESSIVE ANTIRETROVIRAL THERAPY; BROADLY NEUTRALIZING ANTIBODIES; HISTONE DEACETYLASE INHIBITOR; HIGHLY PATHOGENIC SIV; LATENT HIV-1; VIRAL RESERVOIR; IN-VIVO; TREATMENT INTERRUPTION; RALTEGRAVIR INTENSIFICATION AB Antiretroviral therapy is not curative. Given the challenges in providing lifelong therapy to a global population of more than 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the group's strategy. C1 [Deeks, Steven G.; Auerbach, Judith; Henrich, Timothy J.; McCune, Joseph] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Lewin, Sharon R.] Univ Melbourne, Peter Doherty Inst Infect & Immun, Melbourne, Vic, Australia. [Lewin, Sharon R.] Royal Melbourne Hosp, Melbourne, Vic, Australia. [Lewin, Sharon R.] Alfred Hosp, Dept Infect Dis, Melbourne, Vic, Australia. [Lewin, Sharon R.] Monash Univ, Melbourne, Vic, Australia. [Ross, Anna Laura] ANRS, Int & Sci Relat Off, Paris, France. [Ananworanich, Jintanat] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD 20910 USA. [Ananworanich, Jintanat] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD 20817 USA. [Benkirane, Monsef] Univ Montpellier, CNRS UPR 1142, Inst Human Genet, Mol Virol Lab, Montpellier, France. [Cannon, Paula] Univ Southern Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Chomont, Nicolas] Univ Montreal, Fac Med, CRCHUM, Montreal, PQ, Canada. [Chomont, Nicolas] Univ Montreal, Fac Med, Dept Microbiol Infectiol & Immunol, Montreal, PQ, Canada. [Douek, Daniel] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Lifson, Jeffrey D.] Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick Natl Lab, Frederick, MD 21702 USA. [Lo, Ying-Ru] World Hlth Org Reg Off Western Pacific, Manila, Philippines. [Kuritzkes, Daniel; Henrich, Timothy J.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Margolis, David; Henderson, Gail] Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA. [Mellors, John] Univ Pittsburgh, Dept Med, Div Infect Dis, 930 Scaife Hall, Pittsburgh, PA 15260 USA. [Persaud, Deborah] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. [Persaud, Deborah] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Tucker, Joseph D.] Univ North Carolina Project China, Guangzhou, Guangdong, Peoples R China. [Barre-Sinoussi, Francoise] Inst Pasteur, Paris, France. [Alter, Galit; Barouch, Dan H.] MIT & Harvard, Ragon Inst MGH, Boston, MA USA. [Autran, Brigitte] Univ Paris 06, Sorbonne Univ, CIMI, Paris, France. [Autran, Brigitte] CIMI Paris, INSERM, U1135, Paris, France. [Autran, Brigitte] Hop La Pitie Salpetriere, AP HP, Dept Immunol, Paris, France. [Barouch, Dan H.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Behrens, Georg] Hannover Med Sch, Clin Immunol & Rhematol, Hannover, Germany. [Cavazzana, Marina] Hop Necker Enfants Malad, Ctr Invest Clin Biotherapie, Paris, France. [Chen, Zhiwei] Univ Hong Kong, AIDS Inst, Pok Fu Lam, Hong Kong, Peoples R China. [Cohen, Eric A.] Univ Montreal, Inst Rech Clin Montreal, Montreal, PQ, Canada. [Corbelli, Giulio Maria] European AIDS Treatment Grp, Rome, Italy. [Eholie, Serge] Ctr Hosp Univ Treichville, Programme PAC CI, Abidjan, Cote Ivoire. [Eyal, Nir] Harvard TH Chan Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA USA. [Fidler, Sarah] Imperial Coll London, Dept Med, London, England. [Garcia, Laurindo] B Change Grp, Manila, Philippines. [Grossman, Cynthia] NIMH, NIH, Bethesda, MD 20892 USA. [Jefferys, Richard] Treatment Act Grp, New York, NY 10016 USA. [Kiem, Hans-Peter] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA. [Moodley, Keymanthri] Univ Stellenbosch, Dept Med, Ctr Med Eth & Law, Western Cape, South Africa. [Newman, Peter A.] Univ Toronto, Factor Inwentash Fac Social Work, Toronto, ON, Canada. [Nijhuis, Monique] Univ Med Ctr Utrecht, Dept Med Microbiol, Virol, Utrecht, Netherlands. [Nsubuga, Moses Supercharger] Joint Clin Res Ctr, Kampala, Uganda. [Ott, Melanie] Univ Calif San Francisco, Gladstone Inst, San Francisco, CA 94143 USA. [Palmer, Sarah] Univ Sydney, Westmead Millennium Inst Med Res, Sydney, NSW, Australia. [Richman, Douglas] Virginia San Diego Healthcare Syst, San Diego, CA 92161 USA. [Richman, Douglas] Univ Calif San Diego, San Diego, CA 92103 USA. [Saez-Cirion, Asier] Inst Pasteur, Paris, France. [Sharp, Matthew] Independent HIV Educ & Advocacy Consultant, San Francisco, CA USA. [Siliciano, Janet] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Silvestri, Guido] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Singh, Jerome] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Durban, South Africa. [Spire, Bruno] INSERM, UMR S912, Marseille, France. [Taylor, Jeffrey] CARE Collaboratory Community Advisory Board, Palm Springs, CA USA. [Tolstrup, Martin] Aarhus Univ, Inst Clin Med, Aarhus, Denmark. [Valente, Susana] Scripps Res Inst, Dept Immunol & Microbial Sci, Jupiter, FL 33458 USA. [van Lunzen, Jan] ViiV Healthcare, London, England. [Walensky, Rochelle] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wilson, Ira] Brown Univ, Sch Publ Hlth, Dept Hlth Serv Policy & Practice, Providence, RI 02912 USA. [Zack, Jerome] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Deeks, SG (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. EM steven.deeks@ucsf.edu RI Behrens, Georg/Q-4486-2016; Spire, Bruno/F-5546-2013; OI Spire, Bruno/0000-0002-3546-8020; Deeks, Steven/0000-0001-6371-747X; Saez-Cirion, Asier/0000-0003-2406-7536; Lewin, Sharon Ruth/0000-0002-0330-8241 FU federal funds from the NCI/NIH [HHSN261200800001E] FX J.L. is supported in part by federal funds from the NCI/NIH under contract no. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the DHHS, nor does mention of trade names, commercial products or organizations imply endorsement by the U.S. government. The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army, the Department of Defense or the US National Institutes of Health. Y.-R.L. is a World Health Organization (WHO) staff member. The opinions herein are those of the authors and should not be construed as official or representing the views of the WHO. The authors acknowledge T. Rasmussen, T. Mota and M. Crane for assistance with preparation of figures. NR 125 TC 12 Z9 12 U1 16 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD AUG PY 2016 VL 22 IS 8 BP 839 EP 850 DI 10.1038/nm.4108 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA DS7YV UT WOS:000381000200009 PM 27400264 ER PT J AU Wang, WZ Wang, LW Lu, JJ Siedlak, SL Fujioka, H Liang, JJ Jiang, SR Ma, XP Jiang, Z da Rocha, EL Sheng, M Choi, H Lerou, PH Li, H Wang, XL AF Wang, Wenzhang Wang, Luwen Lu, Junjie Siedlak, Sandra L. Fujioka, Hisashi Liang, Jingjing Jiang, Sirui Ma, Xiaopin Jiang, Zhen da Rocha, Edroaldo Lummertz Sheng, Max Choi, Heewon Lerou, Paul H. Li, Hu Wang, Xinglong TI The inhibition of TDP-43 mitochondrial localization blocks its neuronal toxicity SO NATURE MEDICINE LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; FRONTOTEMPORAL LOBAR DEGENERATION; ALZHEIMERS-DISEASE; SPLICING REGULATION; PROTEIN-PROTEIN; TRANSGENIC MICE; MOTOR-NEURONS; RNA TARGETS; MUTATIONS; DEMENTIA AB Genetic mutations in TAR DNA-binding protein 43 (TARDBP, also known as TDP-43) cause amyotrophic lateral sclerosis (ALS), and an increase in the presence of TDP-43 (encoded by TARDBP) in the cytoplasm is a prominent histopathological feature of degenerating neurons in various neurodegenerative diseases. However, the molecular mechanisms by which TDP-43 contributes to ALS pathophysiology remain elusive. Here we have found that TDP-43 accumulates in the mitochondria of neurons in subjects with ALS or frontotemporal dementia (FTD). Disease-associated mutations increase TDP-43 mitochondrial localization. In mitochondria, wild-type (WT) and mutant TDP-43 preferentially bind mitochondria-transcribed messenger RNAs (mRNAs) encoding respiratory complex I subunits ND3 and ND6, impair their expression and specifically cause complex I disassembly. The suppression of TDP-43 mitochondrial localization abolishes WT and mutant TDP-43-induced mitochondrial dysfunction and neuronal loss, and improves phenotypes of transgenic mutant TDP-43 mice. Thus, our studies link TDP-43 toxicity directly to mitochondrial bioenergetics and propose the targeting of TDP-43 mitochondrial localization as a promising therapeutic approach for neurodegeneration. C1 [Wang, Wenzhang; Wang, Luwen; Siedlak, Sandra L.; Jiang, Sirui; Ma, Xiaopin; Jiang, Zhen; Sheng, Max; Choi, Heewon; Wang, Xinglong] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. [Lu, Junjie] Brigham & Womens Hosp, Dept Pediat Newborn Med, 75 Francis St, Boston, MA 02115 USA. [Fujioka, Hisashi] Case Western Reserve Univ, Electron Microscopy Core Facil, Cleveland, OH 44106 USA. [Liang, Jingjing] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. [da Rocha, Edroaldo Lummertz; Li, Hu] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN USA. [Lerou, Paul H.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Wang, XL (reprint author), Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. EM xinglong.wang@case.edu OI Wang, Wenzhang/0000-0003-4426-019X FU US National Institutes of Health [R03AG044680, 1R01NS089604]; US Alzheimer's Association [2014-NIRG-301299]; University Hospitals of Cleveland, USA (SPITZ Innovation Pilot Grant); Eunice Kennedy Shriver National Institute of Child Health and Human Development Brain and Tissue Bank for Developmental Disorders at the University of Maryland, Baltimore, Maryland, USA [HHSN275200900011C, N01-HD-9-0011] FX This study is supported by grants from the US National Institutes of Health (R03AG044680 and 1R01NS089604 to X.W.), the US Alzheimer's Association (2014-NIRG-301299 to X.W.) and the University Hospitals of Cleveland, USA (2012 SPITZ Innovation Pilot Grant to X.W.). Human spinal cord frozen tissues were obtained from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Brain and Tissue Bank for Developmental Disorders at the University of Maryland, Baltimore, Maryland, USA, contract HHSN275200900011C, ref. no. N01-HD-9-0011. We also thank G. Perry and X. Zhu for providing paraffin-embedded human spinal cord tissues. NR 61 TC 5 Z9 5 U1 9 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD AUG PY 2016 VL 22 IS 8 BP 869 EP + DI 10.1038/nm.4130 PG 14 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA DS7YV UT WOS:000381000200012 PM 27348499 ER PT J AU Theurl, I Hilgendorf, I Nairz, M Tymoszuk, P Haschka, D Asshoff, M He, S Gerhardt, LMS Holderried, TAW Seifert, M Sopper, S Fenn, AM Anzai, A Rattik, S McAlpine, C Theurl, M Wieghofer, P Iwamoto, Y Weber, GF Harder, NK Chousterman, BG Arvedson, TL McKee, M Wang, FD Lutz, OMD Rezoagli, E Babitt, JL Berra, L Prinz, M Nahrendorf, M Weiss, G Weissleder, R Lin, HY Swirski, FK AF Theurl, Igor Hilgendorf, Ingo Nairz, Manfred Tymoszuk, Piotr Haschka, David Asshoff, Malte He, Shun Gerhardt, Louisa M. S. Holderried, Tobias A. W. Seifert, Markus Sopper, Sieghart Fenn, Ashley M. Anzai, Atsushi Rattik, Sara McAlpine, Cameron Theurl, Milan Wieghofer, Peter Iwamoto, Yoshiko Weber, Georg F. Harder, Nina K. Chousterman, Benjamin G. Arvedson, Tara L. McKee, Mary Wang, Fudi Lutz, Oliver M. D. Rezoagli, Emanuele Babitt, Jodie L. Berra, Lorenzo Prinz, Marco Nahrendorf, Matthias Weiss, Guenter Weissleder, Ralph Lin, Herbert Y. Swirski, Filip K. TI On-demand erythrocyte disposal and iron recycling requires transient macrophages in the liver SO NATURE MEDICINE LA English DT Article ID RED-BLOOD-CELLS; TISSUE MACROPHAGES; MICROARRAY DATA; CHRONIC DISEASE; MOUSE MODEL; SPI-C; HOMEOSTASIS; HEPCIDIN; ANEMIA; MICE AB Iron is an essential component of the erythrocyte protein hemoglobin and is crucial to oxygen transport in vertebrates. In the steady state, erythrocyte production is in equilibrium with erythrocyte removal(1). In various pathophysiological conditions, however, erythrocyte life span is compromised severely, which threatens the organism with anemia and iron toxicity(2,3). Here we identify an on-demand mechanism that clears erythrocytes and recycles iron. We show that monocytes that express high levels of lymphocyte antigen 6 complex, locus C1 (LY6C1, also known as Ly-6C) ingest stressed and senescent erythrocytes, accumulate in the liver via coordinated chemotactic cues, and differentiate into ferroportin 1 (FPN1, encoded by SLC40A1)-expressing macrophages that can deliver iron to hepatocytes. Monocyte-derived FPN(1+)Tim-4(neg) macrophages are transient, reside alongside embryonically derived T cell immunoglobulin and mucin domain containing 4 (Timd4, also known as Tim-4)(high) Kupffer cells (KCs), and depend on the growth factor Csf1 and the transcription factor Nrf2 (encoded by Nfe2/2). The spleen, likewise, recruits iron-loaded Ly-6C(high) monocytes, but these do not differentiate into iron-recycling macrophages, owing to the suppressive action of Csf2. The accumulation of a transient macrophage population in the liver also occurs in mouse models of hemolytic anemia, anemia of inflammation, and sickle cell disease. Inhibition of monocyte recruitment to the liver during stressed erythrocyte delivery leads to kidney and liver damage. These observations identify the liver as the primary organ that supports rapid erythrocyte removal and iron recycling, and uncover a mechanism by which the body adapts to fluctuations in erythrocyte integrity. C1 [Theurl, Igor; Hilgendorf, Ingo; Nairz, Manfred; He, Shun; Gerhardt, Louisa M. S.; Fenn, Ashley M.; Anzai, Atsushi; Rattik, Sara; McAlpine, Cameron; Iwamoto, Yoshiko; Weber, Georg F.; Harder, Nina K.; Chousterman, Benjamin G.; McKee, Mary; Babitt, Jodie L.; Nahrendorf, Matthias; Weissleder, Ralph; Lin, Herbert Y.; Swirski, Filip K.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Theurl, Igor; Hilgendorf, Ingo; Nairz, Manfred; He, Shun; Gerhardt, Louisa M. S.; Fenn, Ashley M.; Anzai, Atsushi; Rattik, Sara; McAlpine, Cameron; Iwamoto, Yoshiko; Weber, Georg F.; Harder, Nina K.; Chousterman, Benjamin G.; McKee, Mary; Rezoagli, Emanuele; Babitt, Jodie L.; Berra, Lorenzo; Nahrendorf, Matthias; Weissleder, Ralph; Lin, Herbert Y.; Swirski, Filip K.] Harvard Med Sch, Boston, MA 02115 USA. [Theurl, Igor; Hilgendorf, Ingo; Nairz, Manfred; He, Shun; Gerhardt, Louisa M. S.; Fenn, Ashley M.; Anzai, Atsushi; Rattik, Sara; McAlpine, Cameron; Iwamoto, Yoshiko; Weber, Georg F.; Harder, Nina K.; Chousterman, Benjamin G.; Nahrendorf, Matthias; Weissleder, Ralph; Swirski, Filip K.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Theurl, Igor; Tymoszuk, Piotr; Haschka, David; Asshoff, Malte; Seifert, Markus; Weiss, Guenter] Med Univ Innsbruck, Dept Internal Med 6, Infect Dis, Immunol,Rheumatol,Pneumol, Innsbruck, Austria. [Hilgendorf, Ingo] Univ Freiburg, Heart Ctr Freiburg, Freiburg, Germany. [Holderried, Tobias A. W.] Univ Hosp Bonn, Dept Internal Med Oncol Hematol & Rheumatol 3, Bonn, Germany. [Sopper, Sieghart] Med Univ Innsbruck, Dept Internal Med 5, Innsbruck, Austria. [Theurl, Milan] Med Univ Innsbruck, Dept Ophthalmol & Optometry, Innsbruck, Austria. [Wieghofer, Peter; Prinz, Marco] Univ Freiburg, Med Ctr, Inst Neuropathol, Freiburg, Germany. [Wieghofer, Peter] Univ Freiburg, Fac Biol, Freiburg, Germany. [Arvedson, Tara L.] Amgen Inc, Dept Oncol, Thousand Oaks, CA 91320 USA. [McKee, Mary; Babitt, Jodie L.; Lin, Herbert Y.] Massachusetts Gen Hosp, Div Nephrol, Program Membrane Biol, Boston, MA 02114 USA. [Wang, Fudi] Zhejiang Univ, Inst Nutr & Food Safety, Nutr Discovery Innovat Ctr, Dept Nutr,Sch Publ Hlth,Sch Med, Hangzhou, Zhejiang, Peoples R China. [Lutz, Oliver M. D.] Austrian Drug Screening Inst, Innsbruck, Austria. [Rezoagli, Emanuele; Berra, Lorenzo] Massachusetts Gen Hosp, Dept Anaesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Prinz, Marco] Univ Freiburg, BIOSS Ctr Biol Signalling Studies, Freiburg, Germany. [Weissleder, Ralph] Harvard Med Sch, Dept Syst Biol, Boston, MA USA. RP Lin, HY; Swirski, FK (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.; Lin, HY; Swirski, FK (reprint author), Harvard Med Sch, Boston, MA 02115 USA.; Swirski, FK (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.; Lin, HY (reprint author), Massachusetts Gen Hosp, Div Nephrol, Program Membrane Biol, Boston, MA 02114 USA. EM Lin.Herbert@mgh.harvard.edu; fswirski@mgh.harvard.edu FU US National Institutes of Health (NIH) [1R01HL095612, R01HL128264, R56AI104695]; Massachusetts General Hospital's Howard M. Goodman Fellowship [R01DK071837]; Max Kade Foundation; Austrian Science Fund (FWF) [P28302-B30, P24749-B13, HI 1573/1-1, HI 1573/2-1]; German Research Foundation; FWF Erwin Schroedinger Fellowship [J3486-B13]; Boehringer Ingelheim Fonds; National Natural Science Foundation of China [31530034, 31225013] FX This work was supported in part by US National Institutes of Health (NIH) grants 1R01HL095612, R01HL128264, R56AI104695 and the Massachusetts General Hospital's Howard M. Goodman Fellowship (to F.K.S.) and R01DK071837 (to H.Y.L.). I.T. was supported by the Max Kade Foundation and grants by the Austrian Science Fund (FWF) (P28302-B30 and P24749-B13)). I.H. (HI 1573/1-1, HI 1573/2-1) and G.F.W. were supported by the German Research Foundation. M. Nairz was supported by an FWF Erwin Schroedinger Fellowship (J3486-B13). L.M.S.G. and N.K.H. were supported by the Boehringer Ingelheim Fonds. F.W. was supported by the National Natural Science Foundation of China (31530034 and 31225013). We thank D. Capen for help in electron microscopy; N. Bonheur and M. Waring for help with cell sorting; A. Lindau for technical assistance; C. Haerdtner, J. Kornemann, and J. Zou for help with flow cytometry; D. Brown for interpretation of electron microscopy images; C. Robbins for the mouse drawing; and K. Joyes for editing the manuscript. NR 40 TC 8 Z9 8 U1 4 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD AUG PY 2016 VL 22 IS 8 BP 945 EP + DI 10.1038/nm.4146 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA DS7YV UT WOS:000381000200021 PM 27428900 ER PT J AU Li, Y Oosting, M Deelen, P Ricano-Ponce, I Smeekens, S Jaeger, M Matzaraki, V Swertz, MA Xavier, RJ Franke, L Wijmenga, C Joosten, LAB Kumar, V Netea, MG AF Li, Yang Oosting, Marije Deelen, Patrick Ricano-Ponce, Isis Smeekens, Sanne Jaeger, Martin Matzaraki, Vasiliki Swertz, Morris A. Xavier, Ramnik J. Franke, Lude Wijmenga, Cisca Joosten, Leo A. B. Kumar, Vinod Netea, Mihai G. TI Inter-individual variability and genetic influences on cytokine responses to bacteria and fungi SO NATURE MEDICINE LA English DT Article ID CHRONIC MUCOCUTANEOUS CANDIDIASIS; HUMAN IMMUNE-SYSTEM; DISEASE SUSCEPTIBILITY; INFECTIOUS-DISEASE; PROTEIN ABUNDANCE; STAT1 MUTATIONS; LIVER-DISEASE; LOW-FREQUENCY; WHOLE-BLOOD; VARIANTS AB Little is known about the inter-individual variation of cytokine responses to different pathogens in healthy individuals. To systematically describe cytokine responses elicited by distinct pathogens and to determine the effect of genetic variation on cytokine production, we profiled cytokines produced by peripheral blood mononuclear cells from 197 individuals of European origin from the 200 Functional Genomics (200FG) cohort in the Human Functional Genomics Project (http://www.humanfunctionalgenomics.org), obtained over three different years. We compared bacteria- and fungi-induced cytokine profiles and found that most cytokine responses were organized around a physiological response to specific pathogens, rather than around a particular immune pathway or cytokine. We then correlated genome-wide single-nucleotide polymorphism (SNP) genotypes with cytokine abundance and identified six cytokine quantitative trait loci (QTLs). Among them, a cytokine QTL at the NAA35-GOLM1 locus markedly modulated interleukin (IL)-6 production in response to multiple pathogens and was associated with susceptibility to candidemia. Furthermore, the cytokine QTLs that we identified were enriched among SNPs previously associated with infectious diseases and heart diseases. These data reveal and begin to explain the variability in cytokine production by human immune cells in response to pathogens. C1 [Li, Yang; Deelen, Patrick; Ricano-Ponce, Isis; Matzaraki, Vasiliki; Swertz, Morris A.; Franke, Lude; Wijmenga, Cisca; Kumar, Vinod] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. [Oosting, Marije; Smeekens, Sanne; Jaeger, Martin; Joosten, Leo A. B.; Netea, Mihai G.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Nijmegen, Netherlands. [Oosting, Marije; Smeekens, Sanne; Jaeger, Martin; Joosten, Leo A. B.; Netea, Mihai G.] Radboud Univ Nijmegen, Med Ctr, Radboud Ctr Infect Dis, Nijmegen, Netherlands. [Deelen, Patrick; Swertz, Morris A.] Univ Groningen, Univ Med Ctr Groningen, Genom Coordinat Ctr, Groningen, Netherlands. [Xavier, Ramnik J.] Harvard Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA USA. [Xavier, Ramnik J.] Harvard Med Sch, Boston, MA USA. [Xavier, Ramnik J.] Broad Inst MIT & Harvard Univ, Cambridge, MA USA. RP Kumar, V (reprint author), Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.; Netea, MG (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Nijmegen, Netherlands.; Netea, MG (reprint author), Radboud Univ Nijmegen, Med Ctr, Radboud Ctr Infect Dis, Nijmegen, Netherlands. EM v.kumar@umcg.nl; mihai.netea@radboudumc.nl RI Smeekens, Sanne/G-8307-2011; Oosting, Marije/H-7437-2015; Franke, Lude/P-7036-2016; Wijmenga, Cisca/D-2173-2009; OI Smeekens, Sanne/0000-0002-7835-914X; Franke, Lude/0000-0002-5159-8802; Deelen, Patrick/0000-0002-5654-3966 FU ERC Consolidator Grant [3310372]; ERC Advanced Grant (FP)/ERC [2012-322698]; Dutch Digestive Diseases Foundation [MLDS WO11-30]; European Union's Seventh Framework Programme (EU FP7) TANDEM project [HEALTH-F3-2012-305279]; Netherlands Organization for Scientific Research (NWO) VENI grant [863.13.011]; Netherlands Organization for Scientific Research [184021007] FX The authors thank all volunteers from the 200 Functional Genomics cohort of the Human Functional Genomics Project for participation in the study. The authors would like to thank K. McIntyre for editing the final text. This study was partially supported by a ERC Consolidator Grant (3310372) to M.G.N. and by the ERC Advanced Grant (FP/2007-2013/ERC grant 2012-322698 to C.W.), the Dutch Digestive Diseases Foundation (MLDS WO11-30 to C.W. and V.K.), the European Union's Seventh Framework Programme (EU FP7) TANDEM project (HEALTH-F3-2012-305279 to C.W. and V.K.), and a Netherlands Organization for Scientific Research (NWO) VENI grant (863.13.011 to Y.L.). This study made use of data generated by the 'Genome of the Netherlands' project, which is funded by the Netherlands Organization for Scientific Research (grant no. 184021007). The data were made available as a Rainbow Project of BBMRI-NL. NR 54 TC 7 Z9 7 U1 6 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD AUG PY 2016 VL 22 IS 8 BP 952 EP + DI 10.1038/nm.4139 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA DS7YV UT WOS:000381000200022 PM 27376574 ER PT J AU Schiff, D Schrag, D AF Schiff, David Schrag, Deborah TI Living in a material world: tumor-treating fields at the top of the charts SO NEURO-ONCOLOGY LA English DT Editorial Material ID ALTERNATING ELECTRIC-FIELDS; COST-EFFECTIVENESS; GLIOBLASTOMA C1 [Schiff, David] Univ Virginia, Neurooncol Ctr, Box 800432, Charlottesville, VA 22903 USA. [Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Schiff, D (reprint author), Univ Virginia, Neurooncol Ctr, Box 800432, Charlottesville, VA 22903 USA. EM davidschiff@virginia.edu NR 10 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD AUG PY 2016 VL 18 IS 8 BP 1033 EP 1034 DI 10.1093/neuonc/now138 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DV9TT UT WOS:000383285800001 PM 27382117 ER PT J AU Arvold, ND Lee, EQ Mehta, MP Margolin, K Alexander, BM Lin, NU Anders, CK Soffietti, R Camidge, DR Vogelbaum, MA Dunn, IF Wen, PY AF Arvold, Nils D. Lee, Eudocia Q. Mehta, Minesh P. Margolin, Kim Alexander, Brian M. Lin, Nancy U. Anders, Carey K. Soffietti, Riccardo Camidge, D. Ross Vogelbaum, Michael A. Dunn, Ian F. Wen, Patrick Y. TI Updates in the management of brain metastases SO NEURO-ONCOLOGY LA English DT Review DE brain metastases; chemotherapy; stereotactic radiosurgery; surgery; whole brain radiation ID CELL LUNG-CANCER; POSTOPERATIVE RESECTION CAVITY; THERAPY-ONCOLOGY-GROUP; HER2-POSITIVE BREAST-CANCER; NERVOUS-SYSTEM PROGRESSION; QUALITY-OF-LIFE; PHASE-II TRIAL; LAPATINIB PLUS CAPECITABINE; CLINICAL-PRACTICE GUIDELINE; TYROSINE KINASE INHIBITORS AB The clinical management/understanding of brain metastases (BM) has changed substantially in the last 5 years, with key advances and clinical trials highlighted in this review. Several of these changes stem from improvements in systemic therapy, which have led to better systemic control and longer overall patient survival, associated with increased time at risk for developing BM. Development of systemic therapies capable of preventing BM and controlling both intracranial and extracranial disease once BM are diagnosed is paramount. The increase in use of stereotactic radiosurgery alone for many patients with multiple BM is an outgrowth of the desire to employ treatments focused on local control while minimizing cognitive effects associated with whole brain radiotherapy. Complications from BM and their treatment must be considered in comprehensive patient management, especially with greater awareness that the majority of patients do not die from their BM. Being aware of significant heterogeneity in prognosis and therapeutic options for patients with BM is crucial for appropriate management, with greater attention to developing individual patient treatment plans based on predicted outcomes; in this context, recent prognostic models of survival have been extensively revised to incorporate molecular markers unique to different primary cancers. C1 [Arvold, Nils D.] St Lukes Radiat Oncol Associates, St Lukes Canc Ctr, Whiteside Inst Clin Res, Duluth, MN USA. [Arvold, Nils D.] Univ Minnesota, Duluth, MN 55812 USA. [Lee, Eudocia Q.; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. [Lee, Eudocia Q.; Alexander, Brian M.; Lin, Nancy U.; Dunn, Ian F.; Wen, Patrick Y.] Harvard Med Sch, Boston, MA USA. [Mehta, Minesh P.] Univ Maryland, Med Ctr, Dept Radiat Oncol, Baltimore, MD 21201 USA. [Margolin, Kim] City Hope Natl Med Ctr, Dept Med Oncol, Duarte, CA USA. [Alexander, Brian M.] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. [Lin, Nancy U.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Anders, Carey K.] Univ N Carolina, Dept Med, Div Hematol Oncol, Chapel Hill, NC USA. [Soffietti, Riccardo] Univ Turin, Dept Neurol Neurooncol, Turin, Italy. [Camidge, D. Ross] Univ Colorado, Div Med Oncol, Denver, CO 80202 USA. [Vogelbaum, Michael A.] Cleveland Clin, Dept Neurosurg, Cleveland, OH 44106 USA. [Dunn, Ian F.] Brigham & Womens Hosp, Dept Neurosurg, 75 Francis St, Boston, MA 02115 USA. RP Arvold, ND (reprint author), St Lukes Radiat Oncol Associates, St Lukes Canc Ctr, Lakeview Bldg,1001 East Super St,Suite L101, Duluth, MN 55802 USA. EM nils.arvold@slhduluth.com OI mehta, minesh/0000-0002-4812-5713 FU Novocure; Cellectar; Genentech; GlaxoSmithKline; Array Biopharma; Oncothyreon; Kadmon; Novartis; Puma FX There was no specific funding source for the information presented in this review article. M.P.M.: research funding from Novocure and Cellectar. N.U.L.: research funding from Genentech, GlaxoSmithKline, Array Biopharma, Oncothyreon, Kadmon, Novartis, and Puma. NR 149 TC 3 Z9 3 U1 7 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD AUG PY 2016 VL 18 IS 8 BP 1043 EP 1065 DI 10.1093/neuonc/now127 PG 23 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DV9TT UT WOS:000383285800004 PM 27382120 ER PT J AU Shah, K AF Shah, Khalid TI Stem cell-based therapies for tumors in the brain: are we there yet? SO NEURO-ONCOLOGY LA English DT Review DE brain tumors; glioblastoma (GBM); receptors; stem cells; therapeutics ID MESENCHYMAL STROMAL CELLS; NEURAL PROGENITOR CELLS; APOPTOSIS-INDUCING LIGAND; SUICIDE GENE-THERAPY; MALIGNANT GLIOMA; INTRACRANIAL GLIOMA; IN-VITRO; ONCOLYTIC VIROTHERAPY; INTRACEREBRAL GLIOMA; INTRANASAL DELIVERY AB Advances in understanding adult stem cell biology have facilitated the development of novel cell-based therapies for cancer. Recent developments in conventional therapies (eg, tumor resection techniques, chemotherapy strategies, and radiation therapy) for treating both metastatic and primary tumors in the brain, particularly glioblastoma have not resulted in a marked increase in patient survival. Preclinical studies have shown that multiple stem cell types exhibit inherent tropism and migrate to the sites of malignancy. Recent studies have validated the feasibility potential of using engineered stem cells as therapeutic agents to target and eliminate malignant tumor cells in the brain. This review will discuss the recent progress in the therapeutic potential of stem cells for tumors in the brain and also provide perspectives for future preclinical studies and clinical translation. C1 [Shah, Khalid] Harvard Med Sch, Massachusetts Gen Hosp, Stem Cell Therapeut & Imaging Program, Boston, MA USA. [Shah, Khalid] Harvard Med Sch, Massachusetts Gen Hosp, Mol Neurotherapy & Imaging Lab, Boston, MA USA. [Shah, Khalid] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Shah, Khalid] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. [Shah, Khalid] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Shah, K (reprint author), 5403,Bldg 149,13th St, Charlestown, MA 01810 USA. EM kshah@mgh.harvard.edu FU [R01CA138922]; [R01CA173077] FX This work was supported by R01CA138922 and R01CA173077. NR 145 TC 3 Z9 3 U1 9 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD AUG PY 2016 VL 18 IS 8 BP 1066 EP 1078 DI 10.1093/neuonc/now096 PG 13 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DV9TT UT WOS:000383285800005 PM 27282399 ER PT J AU Lee, A Lavoie, B Pan, J Kim, J Zenali, M Wilcox, R Callas, P Velez, M Moses, P Kuo, B Mawe, G AF Lee, A. Lavoie, B. Pan, J. Kim, J. Zenali, M. Wilcox, R. Callas, P. Velez, M. Moses, P. Kuo, B. Mawe, G. TI Gender differences in serotonergic signaling are present in the duodenum in functional dyspepsia SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Meeting Abstract C1 [Lee, A.; Lavoie, B.; Pan, J.; Kim, J.; Zenali, M.; Wilcox, R.; Callas, P.; Velez, M.; Moses, P.; Mawe, G.] Univ Vermont, Burlington, VT USA. [Lee, A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Kuo, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1350-1925 EI 1365-2982 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD AUG PY 2016 VL 28 SU 1 SI SI MA 25 BP 12 EP 13 PG 2 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA DV9VS UT WOS:000383290900026 ER PT J AU Palombo, DJ Keane, MM Verfaellie, M AF Palombo, D. J. Keane, M. M. Verfaellie, M. TI Using future thinking to reduce temporal discounting: Under what circumstances are the medial temporal lobes critical? SO NEUROPSYCHOLOGIA LA English DT Article DE Hippocampus; Amnesia; Temporal discounting; Delay discounting; Semantic future thinking ID MENTAL TIME-TRAVEL; DECISION-MAKING; INTERTEMPORAL CHOICE; EPISODIC PROSPECTION; MEMORY; HIPPOCAMPUS; AMNESIA; EVENTS; PERSPECTIVE; KNOWLEDGE AB The capacity to envision the future plays an important role in many aspects of cognition, including our ability to make optimal, adaptive choices. Past work has shown that the medial temporal lobe (MTL) is necessary for decisions that draw on episodic future thinking. By contrast, little is known about the role of the MTL in decisions that draw on semantic future thinking. Accordingly, the present study investigated whether the MTL contributes to one form of decision making, namely intertemporal choice, when such decisions depend on semantic consideration of the future. In an intertemporal choice task, participants must select either a smaller amount of money that is available in the present or a larger amount of money that would be available at a future date. Amnesic individuals with MTL damage and healthy control participants performed such a task in which, prior to making a choice, they engaged in a semantic generation exercise, wherein they generated items that they would purchase with the future reward. In experiment 1, we found that, relative to a baseline condition involving standard intertemporal choice, healthy individuals were more inclined to select a larger, later reward over a smaller, present reward after engaging in semantic future thinking. By contrast, amnesic participants were paradoxically less inclined to wait for a future reward following semantic future thinking. This finding suggests that amnesics may have had difficulty "tagging" the generated item(s) as belonging to the future. Critically, experiment 2 showed that when the generated items were presented alongside the intertemporal choices, both controls and amnesic participants shifted to more patient choices. These findings suggest that the MTL is not needed for making optimal decisions that draw on semantic future thinking as long as scaffolding is provided to support accurate time tagging. Together, these findings stand to better clarify the role of the MTL in decision making. Published by Elsevier Ltd. C1 [Palombo, D. J.; Keane, M. M.; Verfaellie, M.] VA Boston Healthcare Syst, 150 South Huntington Ave, Boston, MA 02130 USA. [Palombo, D. J.; Keane, M. M.; Verfaellie, M.] Boston Univ, Sch Med, Dept Psychiat, 72 East Concord St, Boston, MA 02118 USA. [Keane, M. M.] Wellesley Coll, Dept Psychol, 106 Cent St, Wellesley, MA 02481 USA. RP Palombo, DJ (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave, Boston, MA 02130 USA. EM palombo@bu.edu FU National Institutes of Mental Health [MH093431]; Clinical Science Research and Development Service of the Department of Veterans Affairs [IO1 CX000925]; Faculty Award from Wellesley College; Canadian Institutes of Health Research Postdoctoral Fellowship Award FX D. J. P., M. M. K. and M. V. designed the research. D. J. P. conducted the research and analyses and wrote the manuscript with input from M. M. K. and M. V. This research was supported by the National Institutes of Mental Health (Grant number: MH093431) and the Clinical Science Research and Development Service of the Department of Veterans Affairs (Grant number: IO1 CX000925). The research was also supported by a Faculty Award from Wellesley College to M. M. K. and a Canadian Institutes of Health Research Postdoctoral Fellowship Award to D. J. P. The authors thank Rose Hopkins and Keely Burke for research assistance. The authors additionally thank the two anonymous reviewers for their insightful comments on the manuscript. The authors declare no conflicts of interest. The contents of this manuscript do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. NR 31 TC 0 Z9 0 U1 7 U2 7 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 AUG PY 2016 VL 89 BP 437 EP 444 DI 10.1016/j.neuropsychologia.2016.07.002 PG 8 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA DV5XD UT WOS:000383003100041 PM 27384755 ER PT J AU Klug, TE Rusan, M Fuursted, K Ovesen, T AF Klug, Tejs Ehlers Rusan, Maria Fuursted, Kurt Ovesen, Therese TI Peritonsillar Abscess: Complication of Acute Tonsillitis or Weber's Glands Infection? SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Review DE pathogenesis; peritonsillar abscess; acute tonsillitis ID A STREPTOCOCCAL PHARYNGITIS; SORE THROAT; OUTPATIENT MANAGEMENT; QUINSY TONSILLECTOMY; NEEDLE ASPIRATION; GENERAL-PRACTICE; FUSOBACTERIUM-NECROPHORUM; ANTIBIOTIC-TREATMENT; PENICILLIN THERAPY; CLINICAL HISTORY AB Objective To review the literature concerning the 2 primary hypotheses put forth to explain the pathogenesis of peritonsillar abscess: the acute tonsillitis hypothesis (peritonsillar abscess is a complication of acute tonsillitis) and the Weber gland hypothesis (peritonsillar abscess is an infection of Weber's glands). Data Sources PubMed, EMBASE. Review Methods Data supporting or negating one hypothesis or the other were elicited from the literature. Conclusions Several findings support the acute tonsillitis hypothesis. First, the 2 main pathogens in peritonsillar abscess have been recovered from pus aspirates and bilateral tonsillar tissues with high concordance rates, suggesting that both tonsils are infected in patients with peritonsillar abscess. Second, studies report signs of acute tonsillitis in the days prior to and at the time of peritonsillar abscess. Third, antibiotic treatment reduces the risk of abscess development in patients with acute tonsillitis. However, some findings suggest involvement of the Weber's glands in peritonsillar abscess pathogenesis. First, high amylase levels have been found in peritonsillar pus. Second, the majority of peritonsillar abscesses are located at the superior tonsillar pole in proximity of the Weber's glands. We propose a unified hypothesis whereby bacteria initially infect the tonsillar mucosa and spread via the salivary duct system to the peritonsillar space, where an abscess is formed. Implications for Practice Our findings support the rationale for antibiotic treatment of patients with severe acute tonsillitis to reduce the risk of abscess development. Improved understanding of peritonsillar abscess pathogenesis is important for the development of efficient prevention strategies. C1 [Klug, Tejs Ehlers; Rusan, Maria; Ovesen, Therese] Aarhus Univ Hosp, Dept Otorhinolaryngol Head & Neck Surg, Aarhus, Denmark. [Rusan, Maria] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Fuursted, Kurt] Statens Serum Inst, Dept Microbiol & Infect Control, Copenhagen, Denmark. RP Klug, TE (reprint author), Aarhus Univ Hosp, Dept Otorhinolaryngol Head & Neck Surg, NBG, Bldg 10,Noerrebrogade 44, DK-8000 Aarhus C, Denmark. EM tejsehlersklug@hotmail.com NR 92 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD AUG PY 2016 VL 155 IS 2 BP 199 EP 207 DI 10.1177/0194599816639551 PG 9 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA DU4OZ UT WOS:000382193700002 PM 27026737 ER PT J AU Doyle, EJ Gratton, MA Varvares, MA AF Doyle, Edward J., III Gratton, Michael Anne Varvares, Mark A. TI Impact of Sensory and Motor Defects on Oral Function in an Animal Model SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT AAO-HNSF Annual Meeting and OTO EXPO CY SEP 27-30, 2015 CL Dallas, TX SP AAO, HNSF DE glossectomy; rat; oral function; surgery; consumption ID HYPOGLOSSAL NERVE; RECONSTRUCTION; FOOD; FLAPS AB Objective To evaluate the combined functional impact on swallowing of tongue sensory and motor loss using a rat model. Study Design Rats underwent selective neurectomies with transection of the motor (hypoglossal) nerve or motor and sensory (lingual) nerves. Postoperative functional parameters were followed for 2 weeks. Setting Translational research. Subjects and Methods Thirty-six adolescent male Wistar rats were divided into 4 groups: anesthetic (n = 6), sham surgery (n = 8), hypoglossal transection (n = 10), and hypoglossal and lingual transection (n = 12). Each morning on postoperative days 1 to 14, the water and food intake were quantified and the animal weighed. Two-way analyses of variance (SigmaPlot; SYSTAT, San Jose, California) were performed with factors of group and postoperative day (POD) to analyze whether a significant difference existed between water intake, pellet consumption, and weight change. Results The hypoglossal and lingual group consumed significantly less water during PODs 1 to 2 and significantly less food during PODs 1 to 3 than any other group. This established a significant difference in body weight between the hypoglossal and lingual group and all other groups for the duration of the study. Measured parameters in the hypoglossal group better approximated those of the control anesthetic and sham groups. Conclusions The addition of a sensory loss to a motor deficit involving the oral tongue results in a measurably significant difference in weight gain, a marker of function, compared with rats with only a motor deficit. Additional studies are needed to determine if there would be similar findings in a model of sensate vs asensate oral tongue reconstruction. C1 [Doyle, Edward J., III; Gratton, Michael Anne] St Louis Univ, Dept Otolaryngol, St Louis, MO 63103 USA. [Varvares, Mark A.] Harvard Med Sch, Dept Otol, Boston, MA USA. [Varvares, Mark A.] Harvard Med Sch, Dept Laryngol, Boston, MA USA. [Varvares, Mark A.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. RP Varvares, MA (reprint author), Massachusetts Eye & Ear, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Mark_varvares@meei.harvard.edu NR 14 TC 0 Z9 0 U1 2 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD AUG PY 2016 VL 155 IS 2 BP 246 EP 251 DI 10.1177/0194599816635629 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA DU4OZ UT WOS:000382193700006 PM 26980910 ER PT J AU Mouilso, ER Tuerk, PW Schnurr, PP Rauch, SAM AF Mouilso, Emily R. Tuerk, Peter W. Schnurr, Paula P. Rauch, Sheila A. M. TI Addressing the Gender Gap: Prolonged Exposure for PTSD in Veterans SO PSYCHOLOGICAL SERVICES LA English DT Article DE effectiveness; female veterans; posttraumatic stress disorder; prolonged exposure therapy ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE PROCESSING THERAPY; TRAUMATIC BRAIN-INJURY; HEALTH-STATUS; SEXUAL TRAUMA; WOMEN; MILITARY; OUTCOMES; FEMALE; CARE AB As the proportion of women serving in the United States military continues to increase, more female veterans are being treated for posttraumatic stress disorder (PTSD) in Department of Veterans Affairs (VA) health care settings. Prolonged Exposure (PE) therapy is an evidence-based treatment for PTSD and is often used in VA settings. However, only a few studies have investigated the effectiveness of PE specifically for female veterans with appropriate power. Results of these studies have varied, with similar effects between female and male veterans on par with civilian effects, and more recently, better outcomes for female veterans receiving PE compared with male veterans. The current study contextualizes the evidence from those studies and considers new data regarding clinical outcomes pre- and posttreatment for a large (N = 325) sample of male and female veterans treated with PE in a PTSD specialty clinic. Results indicate a large statistically significant decrease in PTSD as measured by PTSD Checklist (PCL) scores for both male and female veterans treated with PE (d = 1.33). No difference in effectiveness and no difference in treatment completion rates were found between male and female veterans. Our findings support the effectiveness of PE for the treatment of PTSD in female as well as male veterans. Results are compared and contrasted to previous findings in the literature taking into account heterogeneity in methodological and ecological factors among the studies. Emphasis is placed on context of care issues to further the empirical conversation regarding meeting the mental health needs of female veterans. C1 [Mouilso, Emily R.; Tuerk, Peter W.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Mouilso, Emily R.; Tuerk, Peter W.] Med Univ South Carolina, Charleston, SC USA. [Schnurr, Paula P.] Natl Ctr PTSD, White River Jct, VT USA. [Schnurr, Paula P.] Geisel Sch Med Dartmouth, Hanover, NH USA. [Rauch, Sheila A. M.] Dept Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Rauch, Sheila A. M.] Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. [Mouilso, Emily R.] Charlie Norwood VA Med Ctr, Augusta, GA 30901 USA. RP Mouilso, ER (reprint author), Charlie Norwood VA Med Ctr, Augusta, GA 30901 USA. EM emilymouilso@gmail.com FU Department of Veteran Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences Research and Development FX Dr. Peter W. Tuerk's contribution to this article was partially supported by a Career Development Award (CDA-2) from the Department of Veteran Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences Research and Development (PI: Peter W. Tuerk). NR 54 TC 1 Z9 1 U1 2 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 EI 1939-148X J9 PSYCHOL SERV JI Psychol. Serv. PD AUG PY 2016 VL 13 IS 3 BP 308 EP 316 DI 10.1037/ser0000040 PG 9 WC Psychology, Clinical SC Psychology GA DV7HC UT WOS:000383106000012 PM 26121077 ER PT J AU Marques, L Dixon, L Valentine, SE Borba, CPC Simon, NM Stirman, SW AF Marques, Luana Dixon, Louise Valentine, Sarah E. Borba, Christina P. C. Simon, Naomi M. Stirman, Shannon Wiltsey TI Providers' Perspectives of Factors Influencing Implementation of Evidence-Based Treatments in a Community Mental Health Setting: A Qualitative Investigation of the Training-Practice Gap SO PSYCHOLOGICAL SERVICES LA English DT Article DE implementation; communities; attitudes; evidence-based treatments ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE PROCESSING THERAPY; RANDOMIZED CONTROLLED-TRIAL; EVIDENCE-BASED PSYCHOTHERAPIES; CLINICIAN PERSPECTIVES; BEHAVIORAL TREATMENT; EXPOSURE THERAPY; ASSAULT VICTIMS; PTSD SYMPTOMS; ATTITUDES AB This study aims to elucidate relations between provider perceptions of aspects of the consolidated framework for implementation research (Damschroder et al., 2009) and provider attitudes toward the implementation of evidence-based treatments (EBTs) in an ethnically diverse community health setting. Guided by directed content analysis, we analyzed 28 semistructured interviews that were conducted with providers during the pre-implementation phase of a larger implementation study for cognitive processing therapy for posttraumatic stress disorder (Resick et al., 2008). Our findings extend the existing literature by also presenting provider-identified client-level factors that contribute to providers' positive and negative attitudes toward EBTs. Provider-identified client-level factors include the following: client motivation to engage in treatment, client openness to EBTs, support networks of family and friends, client use of community and government resources, the connection and relationship with their therapist, client treatment adherence, client immediate needs or crises, low literacy or illiteracy, low levels of education, client cognitive limitations, and misconceptions about therapy. These results highlight the relations between provider perceptions of their clients, provider engagement in EBT training, and subsequent adoption of EBTs. We present suggestions for future implementation research in this area. C1 [Marques, Luana] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. [Marques, Luana; Valentine, Sarah E.; Borba, Christina P. C.; Simon, Naomi M.] Harvard Med Sch, Dept Psychiat, Boston, MA USA. [Dixon, Louise] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA USA. [Valentine, Sarah E.; Borba, Christina P. C.; Simon, Naomi M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Stirman, Shannon Wiltsey] US Dept Vet Affairs, Palo Alto, CA USA. [Stirman, Shannon Wiltsey] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Stirman, Shannon Wiltsey] Natl Ctr PTSD, Disseminat & Training Div, Palo Alto, CA USA. RP Marques, L (reprint author), Massachusetts Gen Hosp, Community Psychiat PRIDE, 70 Everett Ave,Suite 516, Chelsea, MA 02150 USA. EM lmarques@mgh.harvard.edu OI Wiltsey Stirman, Shannon/0000-0001-9917-5078 FU National Institutes of Health Grant [K23 MH096029-01A1] FX This study was funded by the National Institutes of Health Grant K23 MH096029-01A1 awarded to Luana Marques. The authors express sincere gratitude to the providers who collaborated in this study and the project's research assistants. NR 63 TC 0 Z9 0 U1 7 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 EI 1939-148X J9 PSYCHOL SERV JI Psychol. Serv. PD AUG PY 2016 VL 13 IS 3 BP 322 EP 331 DI 10.1037/ser0000087 PG 10 WC Psychology, Clinical SC Psychology GA DV7HC UT WOS:000383106000014 PM 27281696 ER PT J AU Henderson, AW Turner, AP Williams, RM Norvell, DC Hakimi, KN Czerniecki, JM AF Henderson, Alison W. Turner, Aaron P. Williams, Rhonda M. Norvell, Daniel C. Hakimi, Kevin N. Czerniecki, Joseph M. TI Sexual Activity After Dysvascular Lower Extremity Amputation SO REHABILITATION PSYCHOLOGY LA English DT Article DE amputation; sexual activity; dysvascular disease; satisfaction with life ID QUALITY-OF-LIFE; LOWER-LIMB AMPUTATION; PAIN GRADE QUESTIONNAIRE; ERECTILE DYSFUNCTION; MAJOR DEPRESSION; SINGLE-ITEM; SELF-REPORT; NATIONAL-SURVEY; ADULT AMPUTEES; PHANTOM PAIN AB Objective: This study examined the prevalence and correlates of sexual activity among individuals experiencing their first dysvascular lower extremity amputation. Design: A prospective cohort was recruited from 4 Veterans Affairs Medical Centers. Of 198 potential participants who met inclusion criteria, 113 (57%) agreed to participate within 7 days of amputation (baseline) and 6 weeks, 4 months, and 12 months post-amputation; 105 completed the sexual activity items at baseline. Measures included self-reported frequency of sexual activity; desire for more or less sexual activity; importance of sexual activity to satisfaction with life; Patient Health Questionnaire-9; Locomotor Capability Index-5; pain intensity/frequency; quality of life. Results: Depending on the time period post-amputation, 11%-24% reported engaging in any sexual activity, although a majority indicated that sexual activity is very important to their satisfaction with life. Frequency of sexual activity increased between 6 weeks and 4 and 12 months post-amputation. In univariate analyses, older age was associated with decreased sexual activity at all time points; at 4 and 12 months, greater mobility was associated with increased sexual activity. In multivariable models, mobility was associated with sexual activity at 4 and 12 months; age and race remained associated with sexual activity at 4 and 12 months, respectively. At all time points, frequency and importance of sexual activity were significantly associated with one another. Conclusions: Although a minority of individuals engaged in any sexual activity during the study period, it remained an important factor in overall satisfaction with life. Younger age and improved mobility were associated with increased sexual activity. Rehabilitation specialists are encouraged to address sexuality and, if relevant, incorporate it into rehabilitation goals. Impact and Implications Although individuals with lower extremity amputation (LEA) endorse continued interest in sexual activity, this important aspect of life is often underemphasized by care providers and researchers alike. This study is the first to examine sexual activity among those with recent LEA longitudinally, evaluating the frequency as well as correlates of sexual activity at four time points in the year following amputation. Consistent with their healthy peers of comparable age, individuals with recent LEA secondary to dysvascular disease continue to identify sexual activity as important to their overall satisfaction with life, although only a minority (depending on the time period post-amputation, between 11 and 24%) report engaging in any sexual activity in the year following amputation. In practice, many rehabilitation care providers often fail to address sexuality and sexual activity explicitly among those with recent dysvascular LEA. Rehabilitation psychologists, physicians and other care providers can play a key role in ensuring sexuality is addressed, possibly framing it within the broader context of activities of daily living (ADLs), particularly as increased mobility is associated with increased frequency of sexual activity. C1 [Henderson, Alison W.] Vet Affairs VA Puget Sound Hlth Care Syst, Ctr Excellence Limb Loss Prevent & Prosthet Engn, Seattle, WA 98108 USA. [Turner, Aaron P.; Williams, Rhonda M.; Hakimi, Kevin N.; Czerniecki, Joseph M.] VA Puget Sound Hlth Care Syst, Rehabil Care Serv, Seattle, WA 98108 USA. [Turner, Aaron P.; Williams, Rhonda M.; Hakimi, Kevin N.; Czerniecki, Joseph M.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Norvell, Daniel C.] Spectrum Res Inc, Tacoma, WA USA. RP Turner, AP (reprint author), VA Puget Sound Hlth Care Syst, RCS-117,1660 South Columbian Way, Seattle, WA 98108 USA. EM Aaron.Turner@va.gov FU U.S. Department of Veterans Affairs, Office of Research and Development, Rehabilitation Research and Development Service [A41241, B4927W] FX This work was supported by Merit Review Award A41241 and Career Development Award B4927W from the U.S. Department of Veterans Affairs, Office of Research and Development, Rehabilitation Research and Development Service. The contents do not represent the views of the U.S. Department of Veterans Affairs or the U.S. government. NR 66 TC 0 Z9 0 U1 7 U2 7 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0090-5550 EI 1939-1544 J9 REHABIL PSYCHOL JI Rehabil. Psychol. PD AUG PY 2016 VL 61 IS 3 BP 260 EP 268 DI 10.1037/rep0000087 PG 9 WC Psychology, Clinical; Rehabilitation SC Psychology; Rehabilitation GA DV9HR UT WOS:000383251900005 PM 27253221 ER PT J AU Dhakal, LP Sen, A Stanko, CM Rawal, B Heckman, MG Hoyne, JB Dimberg, EL Freeman, ML Ng, LK Rabinstein, AA Freeman, WD AF Dhakal, Laxmi P. Sen, Ayan Stanko, Carlene M. Rawal, Bhupendra Heckman, Michael G. Hoyne, Jonathan B. Dimberg, Elliot L. Freeman, Michelle L. Ng, Lauren K. Rabinstein, Alejandro A. Freeman, William D. TI Early Absent Pupillary Light Reflexes After Cardiac Arrest in Patients Treated with Therapeutic Hypothermia SO THERAPEUTIC HYPOTHERMIA AND TEMPERATURE MANAGEMENT LA English DT Article ID INTERNATIONAL LIAISON COMMITTEE; EMERGENCY CARDIOVASCULAR CARE; AMERICAN-HEART-ASSOCIATION; COMATOSE SURVIVORS; CARDIOPULMONARY-RESUSCITATION; ISCHEMIC COMA; PROGNOSTICATION; PREDICTION; GUIDELINES; STATEMENT AB Loss of pupillary light reactivity is one recognized indicator of poor prognosis after cardiopulmonary resuscitation (CPR). However, drug overdose, low cardiac output, and/or resuscitation drugs can lead to impaired pupillary light reflex. To investigate pupillary light reflex status before therapeutic hypothermia (TH) in relation to neurological outcome, we retrospectively reviewed the data of a prospectively implemented TH protocol in patients with cardiac arrest (CA) at Mayo Clinic in Jacksonville, Florida (January 2006-January 2012), and Mayo Clinic in Scottsdale, Arizona (August 2010-March 2014). During this period, all CA patients who underwent hypothermia were included. These patients were selected from an institutional database and hypothermia data set. The Cerebral Performance Category (CPC) at time of discharge was our primary outcome measure. A CPC of 1 to 2 was defined as good outcome and a CPC from 3 to 5 was defined as poor outcome. We identified 99 patients who had CA treated with TH. Twenty-nine patients (29%) had pupils that were nonreactive to light on admission examination before TH, eight of whom later had return of pupil reactivity by day 3. Two of these 29 patients (6.9%) had good outcome, compared to 24 of 70 patients (34.3%) with pupils that were reactive to light (p=0.005). Both of these patients had CA after illicit drug overdose. Early nonreactive pupils occurred in almost a third of patients after CPR and before TH in our patient population. Recovery of pupillary light reactivity is possible, and in a small minority of those cases (particularly when CA is preceded by the use of illicit drugs), a good outcome can be achieved. C1 [Dhakal, Laxmi P.; Freeman, Michelle L.; Ng, Lauren K.; Freeman, William D.] Mayo Clin, Dept Crit Care, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. [Dhakal, Laxmi P.; Dimberg, Elliot L.; Ng, Lauren K.; Freeman, William D.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Sen, Ayan] Mayo Clin, Dept Pulm & Crit Care Med, Phoenix, AZ USA. [Stanko, Carlene M.] Mayo Clin, CRISP, Jacksonville, FL 32224 USA. [Rawal, Bhupendra; Heckman, Michael G.] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Jacksonville, FL 32224 USA. [Hoyne, Jonathan B.] Mayo Clin, Dept Lab Med & Pathol, Jacksonville, FL 32224 USA. [Ng, Lauren K.; Freeman, William D.] Mayo Clin, Dept Neurosurg, Jacksonville, FL 32224 USA. [Rabinstein, Alejandro A.] Mayo Clin, Dept Crit Care, Rochester, MN USA. [Rabinstein, Alejandro A.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Dhakal, Laxmi P.] Wesley Med Ctr, Neurocrit Care Unit, Wichita, KS USA. [Rawal, Bhupendra] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Freeman, WD (reprint author), Mayo Clin, Dept Crit Care, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. EM freeman.william1@mayo.edu NR 21 TC 1 Z9 1 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2153-7658 EI 2153-7933 J9 THER HYPOTHERMIA TEM JI Ther. Hypothermia Temp. Manag. PD AUG PY 2016 VL 6 IS 3 BP 116 EP 121 DI 10.1089/ther.2015.0035 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA DV9RC UT WOS:000383277700003 PM 27135180 ER PT J AU Bader, MK Guanci, MM Figueroa, SA Brophy, GM Laux, C AF Bader, Mary Kay Guanci, Mary McKenna Figueroa, Stephen A. Brophy, Gretchen M. Laux, Chris TI Clinical Q & A: Translating Therapeutic Temperature Management from Theory to Practice SO THERAPEUTIC HYPOTHERMIA AND TEMPERATURE MANAGEMENT LA English DT Article ID HOSPITAL CARDIAC-ARREST; HYPOTHERMIA; THROMBOSIS; RESUSCITATION; SEIZURES C1 [Bader, Mary Kay] Mission Hosp, Mission Viejo, CA 92691 USA. [Guanci, Mary McKenna] Massachusetts Gen Hosp, Neurosci Intens Care, Boston, MA 02114 USA. [Figueroa, Stephen A.] Univ Texas Southwestern Med Ctr Dallas, Div Neurocrit Care, Dallas, TX 75390 USA. [Brophy, Gretchen M.] Virginia Commonwealth Univ, Med Coll Virginia Campus, Richmond, VA USA. [Laux, Chris] Harborview Med Ctr, Seattle, WA USA. RP Bader, MK (reprint author), Mission Hosp, Mission Viejo, CA 92691 USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2153-7658 EI 2153-7933 J9 THER HYPOTHERMIA TEM JI Ther. Hypothermia Temp. Manag. PD AUG PY 2016 VL 6 IS 3 BP 146 EP 149 DI 10.1089/ther.2016.29016.mkb PG 4 WC Critical Care Medicine SC General & Internal Medicine GA DV9RC UT WOS:000383277700008 PM 27504625 ER PT J AU Lanuti, M AF Lanuti, Michael TI Managing Controversial Issues in Thoracic Surgery Preface SO THORACIC SURGERY CLINICS LA English DT Editorial Material C1 [Lanuti, Michael] Harvard Med Sch, Massachusetts Gen Hosp, Div Thorac Surg, Thorac Oncol,Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. RP Lanuti, M (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Div Thorac Surg, Thorac Oncol,Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM mlanuti@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 3 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1547-4127 J9 THORAC SURG CLIN JI Thorac. Surg. Clin. PD AUG PY 2016 VL 26 IS 3 BP IX EP IX DI 10.1016/j.thorsurg.2016.05.001 PG 1 WC Respiratory System; Surgery SC Respiratory System; Surgery GA DT2ST UT WOS:000381331400001 PM 27427531 ER PT J AU Lanuti, M AF Lanuti, Michael TI Surgical Management of Oligometastatic Non-Small Cell Lung Cancer SO THORACIC SURGERY CLINICS LA English DT Article DE Oligometastases; Metastases; Non-small lung cancer; Surgery; Metastectomy ID PHASE-II-TRIAL; SYNCHRONOUS BRAIN METASTASES; ISOLATED ADRENAL METASTASIS; TNM STAGE GROUPINGS; LAPAROSCOPIC ADRENALECTOMY; PROGNOSTIC-FACTORS; CEREBRAL METASTASIS; CARCINOMA; RESECTION; SURVIVAL AB Patients harboring stage IV non-small cell lung cancer represent a heterogeneous population with limited life expectancy. Targeted chemotherapy and immunotherapy have improved median survival for a minority of patients. A subset of patients with solitary foci of metastatic disease appears to have improved survival compared to others with stage IV NSCLC. The role of aggressive local control with curative intent for all disease sites in synchronous oligometastatic disease lacks randomized data; however, published retrospective series from single institutions suggest improved survival in highly selected patients (11-30%, 5-year survival) with low morbidity and mortality <2%. C1 [Lanuti, Michael] Harvard Med Sch, Massachusetts Gen Hosp, Div Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. RP Lanuti, M (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Div Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM MLanuti@mgh.harvard.edu NR 47 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1547-4127 J9 THORAC SURG CLIN JI Thorac. Surg. Clin. PD AUG PY 2016 VL 26 IS 3 BP 287 EP + DI 10.1016/j.thorsurg.2016.04.002 PG 9 WC Respiratory System; Surgery SC Respiratory System; Surgery GA DT2ST UT WOS:000381331400006 PM 27427523 ER PT J AU Sihag, S Muniappan, A AF Sihag, Smita Muniappan, Ashok TI Lymph Node Dissection and Pulmonary Metastasectomy SO THORACIC SURGERY CLINICS LA English DT Article DE Lymph node; Lung; Metastasectomy ID RENAL-CELL CARCINOMA; LUNG METASTASECTOMY; COLORECTAL ADENOCARCINOMA; SURGICAL RESECTION; PROGNOSTIC-FACTOR; BREAST-CANCER; SURVIVAL; INVOLVEMENT; EXPERIENCE; LYMPHADENECTOMY AB Unexpected lymph node involvement is observed in approximately 20% of all patients undergoing pulmonary metastasectomy. Lymph node metastasis is often associated with decreased survival in patients with pulmonary metastases. The incidence of lymph node involvement is related to a variety of patient and tumor variables. This article reviews the indications and role for lymph node assessment at pulmonary metastasectomy. C1 [Sihag, Smita; Muniappan, Ashok] Harvard Med Sch, Massachusetts Gen Hosp, Dept Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. RP Muniappan, A (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM amuniappan@partners.org NR 36 TC 0 Z9 0 U1 3 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1547-4127 J9 THORAC SURG CLIN JI Thorac. Surg. Clin. PD AUG PY 2016 VL 26 IS 3 BP 315 EP + DI 10.1016/j.thorsurg.2016.04.004 PG 10 WC Respiratory System; Surgery SC Respiratory System; Surgery GA DT2ST UT WOS:000381331400009 PM 27427526 ER PT J AU Edwards, KS Parish, SJ Rosen, RC Garvert, DW Spangler, SL Ruzek, JI AF Edwards, Katharine S. Parish, Sharon J. Rosen, Raymond C. Garvert, Donn W. Spangler, Shana L. Ruzek, Josef I. TI A Standardized Patient Methodology to Assess Cognitive-Behavioral Therapy (CBT) Skills Performance: Development and Testing in a Randomized Controlled Trial of Web-Based Training SO TRAINING AND EDUCATION IN PROFESSIONAL PSYCHOLOGY LA English DT Article DE dissemination; training; assessment; standardized patient; objective standardized clinical examination (OSCE) ID STRUCTURED CLINICAL EXAMINATION; SUBSTANCE-ABUSE; PROFESSIONAL PSYCHOLOGY; COMPETENCE BENCHMARKS; TREATMENT PROVIDERS; INTERVENTION; PSYCHIATRY; IMPLEMENTATION; DISSEMINATION; SCALE AB Competency-based training is increasingly important in mental health as practitioners are trained in the use of evidence-based treatments for posttraumatic stress disorder (PTSD) and other disorders. Clinical skills according to this model are assessed in various ways, including the use of standardized patient (SP) interviews. This study investigated the reliability and feasibility of using a telephone-based SP interview to evaluate cognitive-behavioral therapy (CBT) skills within a large, randomized trial of online training. This paper describes the development of a standardized SP methodology for the larger study, including case illustration, SP training, development of trainee skills assessment metrics, and rater training. A post hoc substudy evaluated SP performance across time. For the larger study, 2 out of 3 skills assessment metrics showed satisfactory performance and demonstrated consistently good interitem and interrater reliability. The substudy found that SPs were adherent and faithful to their intended character, with little evidence of performance drift. Based on these findings, telephone SP methodologies are a promising technology for large-scale clinical skills assessment in psychology. C1 [Edwards, Katharine S.] Stanford Univ, Stanford, CA 94305 USA. [Parish, Sharon J.] Weill Cornell Med Sch, New York, NY USA. [Parish, Sharon J.] NewYork Presbyterian Hosp, Med Serv, Westchester Div, New York, NY USA. [Rosen, Raymond C.] New England Res Inst Inc, Watertown, MA USA. [Garvert, Donn W.; Ruzek, Josef I.] VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Menlo Pk, CA USA. [Spangler, Shana L.] VA Greater Los Angeles Healthcare Syst, PTSD, North Hills, CA USA. RP Edwards, KS (reprint author), Stanford Univ, Dept Cardiovasc Med, 300 Pasteur Dr,Room H2103, Stanford, CA 94305 USA. EM ksedwards@stanford.edu NR 49 TC 0 Z9 0 U1 6 U2 6 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1931-3918 EI 1931-3926 J9 TRAIN EDUC PROF PSYC JI Train. Educ. Prof. Psychol. PD AUG PY 2016 VL 10 IS 3 BP 149 EP 156 DI 10.1037/tep0000119 PG 8 WC Psychology, Educational SC Psychology GA DV7HQ UT WOS:000383107400004 ER PT J AU Kauth, MR Shipherd, JC Barrera, TL Ortigo, K Jones, KR AF Kauth, Michael R. Shipherd, Jillian C. Barrera, Terri L. Ortigo, Kile Jones, Kenneth R. TI Trainees' Perceptions of the Veterans Health Administration Interprofessional Psychology Fellowships in Lesbian, Gay, Bisexual, and Transgender Health SO TRAINING AND EDUCATION IN PROFESSIONAL PSYCHOLOGY LA English DT Article DE LGBT; veterans; training; psychology; VHA ID CARE; COMPETENCE; PROGRAMS; STUDENTS; BIAS AB To improve the capacity to provide quality health care to lesbian, gay, bisexual and transgender (LGBT) veterans and promote LGBT cultural competence among clinical staff, the United States Veterans Health Administration (VHA) competitively awarded 9 1-year interprofessional postdoctoral psychology fellowships in LGBT health. The interprofessional training model, which involves working with and learning from other disciplines, mirrors the VHA's approach to integrate LGBT services across clinical programs. Fellows' experiences and satisfaction with their training were examined for the first 2 years of the fellowships. Despite variability in clinical and staff educational activities across sites, all fellows reported strong satisfaction with their training experience. The fellows described considerable exposure to other disciplines, working most often with primary care physicians, nurses, and social workers in addition to psychologists. Fellows most enjoyed creating new clinical services and programs for LGBT veterans that would remain after their fellowship year. Consistent with VHA's goal for training programs, the majority of fellows planned to remain in the federal health-care system, having accepted staff positions at a VHA facility or other federal agency. The VHA psychology fellowships in LGBT health appear to be feasible and successful and may serve as a model for fellowships in LGBT health in other agencies or for other disciplines such as primary care, social work, nursing, or endocrinology. C1 [Kauth, Michael R.; Shipherd, Jillian C.; Jones, Kenneth R.] Vet Hlth Adm, Washington, DC USA. [Kauth, Michael R.; Barrera, Terri L.] Vet Affairs South Cent Mental Illness Res Educ &, Houston, TX USA. [Kauth, Michael R.; Barrera, Terri L.] Vet Affairs Hlth Serv Res & Dev Ctr Innovat Qual, Houston, TX USA. [Kauth, Michael R.] Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. [Shipherd, Jillian C.] Vet Affairs Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Shipherd, Jillian C.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Barrera, Terri L.] Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Ortigo, Kile] Vet Affairs Palo Alto Healthcare Syst, Natl Ctr PTSD, Palo Alto, CA USA. [Ortigo, Kile] Vet Res Inst, Palo Alto, CA USA. RP Kauth, MR (reprint author), Michael E DeBakey VA Med Ctr, Vet Affairs152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM Michael.Kauth@va.gov FU United States Veterans Affairs South Central Mental Illness Research, Education and Clinical Center; Houston Veterans Affairs Health Services Research and Development Center for Innovations in Quality, Effectiveness and Safety [CIN13-413] FX THIS WORK WAS SUPPORTED in part by the United States Veterans Affairs South Central Mental Illness Research, Education and Clinical Center and the Houston Veterans Affairs Health Services Research and Development Center for Innovations in Quality, Effectiveness and Safety (CIN13-413). NR 19 TC 0 Z9 0 U1 4 U2 4 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1931-3918 EI 1931-3926 J9 TRAIN EDUC PROF PSYC JI Train. Educ. Prof. Psychol. PD AUG PY 2016 VL 10 IS 3 BP 165 EP 170 DI 10.1037/tep0000123 PG 6 WC Psychology, Educational SC Psychology GA DV7HQ UT WOS:000383107400006 ER PT J AU Liu, QQ Tomaszewicz, K Hutchinson, L Hornick, JL Woda, B Yu, HB AF Liu, Qingqing Tomaszewicz, Keith Hutchinson, Lloyd Hornick, Jason L. Woda, Bruce Yu, Hongbo TI Somatic mutations in histiocytic sarcoma identified by next generation sequencing SO VIRCHOWS ARCHIV LA English DT Article DE Histiocytic sarcoma; Next generation sequencing; Somatic mutations; BRAF proto-oncogene ID BRAF MUTATIONS; SIGNALING PATHWAY; LUNG-CANCER; CELL; POLYMORPHISMS; CHEMOTHERAPY; NEOPLASMS; CARCINOMA; MELANOMA; LEUKEMIA AB Histiocytic sarcoma is a rare malignant neoplasm of presumed hematopoietic origin showing morphologic and immunophenotypic evidence of histiocytic differentiation. Somatic mutation importance in the pathogenesis or disease progression of histiocytic sarcoma was largely unknown. To identify somatic mutations in histiocytic sarcoma, we studied 5 histiocytic sarcomas [3 female and 2 male patients; mean age 54.8 (20-72), anatomic sites include lymph node, uterus, and pleura] and matched normal tissues from each patient as germ line controls. Somatic mutations in 50 "Hotspot" oncogenes and tumor suppressor genes were examined using next generation sequencing. Three (out of five) histiocytic sarcoma cases carried somatic mutations in BRAF. Among them, G464V [variant frequency (VF) of 43.6 %] and G466R (VF of 29.6 %) located at the P loop potentially interfere with the hydrophobic interaction between P and activating loops and ultimately activation of BRAF. Also detected was BRAF somatic mutation N581S (VF of 7.4 %), which was located at the catalytic loop of BRAF kinase domain: its role in modifying kinase activity was unclear. A similar mutational analysis was also performed on nine acute monocytic/monoblastic leukemia cases, which did not identify any BRAF somatic mutations. Our study detected several BRAF mutations in histiocytic sarcomas, which may be important in understanding the tumorigenesis of this rare neoplasm and providing mechanisms for potential therapeutical opportunities. C1 [Liu, Qingqing; Tomaszewicz, Keith; Hutchinson, Lloyd; Woda, Bruce; Yu, Hongbo] UMass Mem Med Ctr, Worcester, MA 01605 USA. [Liu, Qingqing; Tomaszewicz, Keith; Hutchinson, Lloyd; Woda, Bruce; Yu, Hongbo] Univ Massachusetts, Sch Med, Worcester, MA 01655 USA. [Liu, Qingqing] Univ Texas MD Anderson Canc Ctr, Dept Pathol, 1515 Holcombe Blvd, Houston, TX 77030 USA. [Hornick, Jason L.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Yu, Hongbo] VA Boston Healthcare Syst, Pathol & Lab Med Serv, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. RP Yu, HB (reprint author), UMass Mem Med Ctr, Worcester, MA 01605 USA.; Yu, HB (reprint author), Univ Massachusetts, Sch Med, Worcester, MA 01655 USA.; Yu, HB (reprint author), VA Boston Healthcare Syst, Pathol & Lab Med Serv, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM Hongbo.Yu@va.gov NR 34 TC 1 Z9 1 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0945-6317 EI 1432-2307 J9 VIRCHOWS ARCH JI Virchows Arch. PD AUG PY 2016 VL 469 IS 2 BP 233 EP 241 DI 10.1007/s00428-016-1965-2 PG 9 WC Pathology SC Pathology GA DU4DL UT WOS:000382162100012 PM 27259537 ER PT J AU Weber, ML Liang, MC Flaherty, KT Heier, JS AF Weber, Marissa L. Liang, Michelle C. Flaherty, Keith T. Heier, Jeffrey S. TI Subretinal Fluid Associated With MEK Inhibitor Use in the Treatment of Systemic Cancer SO JAMA OPHTHALMOLOGY LA English DT Article ID MELANOMA; RETINOPATHY; TOXICITIES; MUTATIONS; PATHWAY; BRAF AB IMPORTANCE The use of mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitors has become more common in the treatment of systemic cancer. These agents have been associated with a central serous-like retinopathy in some patients. Recognition of such retinal findings and the relatively benign nature of these events is important to avoid unnecessary intervention, including the cessation of a potentially life-prolonging medication. OBJECTIVES To evaluate the presence and characteristics of subretinal fluid (SRF) associated with the use of MEK inhibitors in the treatment of systemic cancer and to correlate the presence of SRF with visual acuity and symptoms over time. DESIGN, SETTING, AND PARTICIPANTS Post hoc analysis was conducted of prospectively collected data from 51 patients with locally advanced or metastatic cancer undergoing treatment with the MEK inhibitor binimetinib in 1 of 4 clinical trials. All clinical trial participants underwent complete ophthalmic examination by retina specialists at a private practice in Boston, Massachusetts, and were monitored between February 29, 2012, and January 8, 2014. The examination included Snellen-measured visual acuity, dilated fundus examination, and spectral-domain optical coherence tomography at baseline, biweekly for 2 months, then monthly for the remainder of their trial participation. Post hoc design and data analysis were performed between December 1, 2013, and June 20, 2014. MAIN OUTCOMES AND MEASURES Visual symptoms, visual acuity, fundus appearance, and the presence and characteristics of SRF noted on optical coherence tomography. The characteristics of angiograms performed at the discretion of the treating physician were reviewed. RESULTS Of the 51 participants, 18 (35%) were men; the mean (SD) age was 60 (13) years (range, 32-87 years). Forty-six (90%) study participants developed SRF during the study period, with 9 (20%) experiencing symptoms at any point. The mean (SD) central retinal thickness of 39 study participants who developed SRF at the first visit increased from 280 (26) mu m at baseline to 316 (43) mu m at the first visit after starting binimetinib treatment (paired t test, P < .001). On examination, SRF appeared as elevated, yellow-orange pockets in the fovea and/or along the arcades. Corresponding optical coherence tomographic imaging revealed SRF beneath the interdigitation zone. The fovea was affected in 37 of 46 (80%) individuals; the location of SRF accumulation varied. Visual symptoms were mild and mainly transient, occurring in 9 participants with SRF (20%; 95% CI, 10%-33%). Only 2 participants (4%) were found to have SRF at the last study visit after discontinuation of treatment with binimetinib. Both had Snellen-measured visual acuity of 20/25 or better. CONCLUSIONS AND RELEVANCE The presence of SRF was common in study participants undergoing treatment with the MEK inhibitor binimetinib. Visual symptoms were mild and mainly transient. The presence of SRF did not lead to permanent ocular sequelae. Cessation of life-extending treatment with MEK inhibitors is not indicated when SRF is present. C1 [Weber, Marissa L.; Liang, Michelle C.; Heier, Jeffrey S.] Ophthalm Consultants Boston, 50 Staniford St,Ste 600, Boston, MA 02114 USA. [Weber, Marissa L.] Walter Reed Natl Mil Med Ctr, Ophthalmol Serv, Bethesda, MD USA. [Liang, Michelle C.] Tufts Med Ctr, New England Eye Ctr, Boston, MA USA. [Flaherty, Keith T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Heier, JS (reprint author), Ophthalm Consultants Boston, 50 Staniford St,Ste 600, Boston, MA 02114 USA. EM jsheier@eyeboston.com FU Aerpio; Alcon/LPath; Allergan; Avalanche; Bayer; EyeGate; Foresight Biotherapeutics; Forsight Vision4; Genentech; Icon Therapeutics; Janssen RD; Kala Pharmaceuticals; Kanghong; Kato Pharmaceuticals; Novartis Pharmaceuticals; Ohr Pharmaceuticals; QLT; Regeneron; RetroSense; Santen; Shire; Stealth Biotherapeutics; Thrombogenics; Vision Medicines; Xcovery; Acucela; Astellas; Corcept; Ophthotech; Sanofi/Genzyme FX Dr Heier is a paid consultant for Aerpio, Alcon/LPath, Allergan, Avalanche, Bayer, EyeGate, Foresight Biotherapeutics, Forsight Vision4, Genentech, Icon Therapeutics, Janssen R&D, Kala Pharmaceuticals, Kanghong, Kato Pharmaceuticals, Novartis Pharmaceuticals, Ohr Pharmaceuticals, QLT, Regeneron, RetroSense, Santen, Shire, Stealth Biotherapeutics, Thrombogenics, Vision Medicines, and Xcovery. He receives research grants from Acucela, Alcon/LPath, Allergan, Astellas, Corcept, Genentech, Kala Pharmaceuticals, Kato Pharmaceuticals, Novartis Pharmaceuticals, Ohr Pharmaceuticals, Ophthotech, QLT, Regeneron, Sanofi/Genzyme, Stealth Biotherapeutics, and Thrombogenics. He owns stock in and is on the Board of Directors for Ocular Therapeutix. Dr Flaherty has received an honorarium as a consultant for Novartis. No other disclosures were reported. NR 16 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD AUG PY 2016 VL 134 IS 8 BP 855 EP 862 DI 10.1001/jamaophthalmol.2016.0090 PG 8 WC Ophthalmology SC Ophthalmology GA DT1AD UT WOS:000381213200005 PM 27309887 ER PT J AU Christophersen, IE Yin, XY Larson, MG Lubitz, SA Magnani, JW McManus, DD Ellinor, PT Benjamin, EJ AF Christophersen, Ingrid E. Yin, Xiaoyan Larson, Martin G. Lubitz, Steven A. Magnani, Jared W. McManus, David D. Ellinor, Patrick T. Benjamin, Emelia J. TI A comparison of the CHARGE-AF and the CHA(2)DS(2)-VASc risk scores for prediction of atrial fibrillation in the Framingham Heart Study SO AMERICAN HEART JOURNAL LA English DT Article ID PROPORTIONAL HAZARDS MODEL; AFRICAN-AMERICANS; SURVIVAL ANALYSIS; COMPETING RISKS; ISCHEMIC-STROKE; CHADS(2); COHORT; VALIDATION; OUTCOMES; SUBDISTRIBUTION AB Background Atrial fibrillation (AF) affects more than 33 million individuals worldwide and increases risks of stroke, heart failure, and death. The CHARGE-AF risk score was developed to predict incident AF in three American cohorts and it was validated in two European cohorts. The CHA(2)DS(2)-VASc risk score was derived to predict risk of stroke, peripheral embolism, and pulmonary embolism in individuals with AF, but it has been increasingly used for AF risk prediction. We compared CHARGE-AF risk score versus CHA(2)DS(2)-VASc risk score for incident AF risk in a community-based cohort. Methods and Results We studied Framingham Heart Study participants aged 46 to 94 years without prevalent AF and with complete covariates. We predicted AF risk using Fine-Gray proportional sub-distribution hazards regression. We used the Wald chi(2) statistic for model fit, C-statistic for discrimination, and Hosmer-Lemeshow (HL) chi(2) statistic for calibration. We included 9722 observations (mean age 63.9 +/- 10.6 years, 56% women) from 4548 unique individuals: 752 (16.5%) developed incident AF and 793 (17.4%) died. The mean CHARGE-AF score was 12.0 +/- 1.2 and the sub-distribution hazard ratio (sHR) for AF per unit increment was 2.15 (95% CI, 99-131%; P <.0001). The mean CHA(2)DS(2)-VASc score was 2.0 +/- 1.5 and the sHR for AF per unit increment was 1.43 (95% CI, 37%-51%; P<.0001). The CHARGE-AF model had better fit than CHA(2)DS(2)-VASc (Wald chi(2) = 403 vs 209, both with 1 df), improved discrimination (C-statistic = 0.75, 95% CI, 0.73-0.76 vs C-statistic = 0.71, 95% CI, 0.69-0.73), and better calibration (HL chi(2) = 5.6, P =.69 vs HL chi(2) = 28.5, P <.0001). Conclusion The CHARGE-AF risk score performed better than the CHA(2)DS(2)-VASc risk score at predicting AF in a community-based cohort. C1 [Christophersen, Ingrid E.; Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Christophersen, Ingrid E.; Lubitz, Steven A.; Ellinor, Patrick T.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Christophersen, Ingrid E.] Vestre Viken Hosp Trust, Brum Hosp, Dept Med Res, Drammen, Norway. [Yin, Xiaoyan; Larson, Martin G.; Magnani, Jared W.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA. [Yin, Xiaoyan; Larson, Martin G.; Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Boston, MA 02215 USA. [Yin, Xiaoyan; Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [McManus, David D.] Univ Massachusetts, Sch Med, Dept Med, Cardiovasc Med Div, Worcester, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Boston, MA USA. RP Benjamin, EJ (reprint author), Boston Univ, Sch Med, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.; Benjamin, EJ (reprint author), Boston Univ, Sch Publ Hlth, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM emelia@bu.edu FU Bayer HealthCare FX Dr Ellinor is a principal investigator on a grant from Bayer HealthCare to the Broad Institute. NR 52 TC 1 Z9 1 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD AUG PY 2016 VL 178 BP 45 EP 54 DI 10.1016/j.ahj.2016.05.004 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DT6JK UT WOS:000381590300006 PM 27502851 ER PT J AU Vemulapalli, S Hellkamp, AS Jones, WS Piccini, JP Mahaffey, KW Becker, RC Hankey, GJ Berkowitz, SD Nessel, CC Breithardt, G Singer, DE Fox, KAA Patel, MR AF Vemulapalli, Sreekanth Hellkamp, Anne S. Jones, W. Schuyler Piccini, Jonathan P. Mahaffey, Kenneth W. Becker, Richard C. Hankey, Graeme J. Berkowitz, Scott D. Nessel, Christopher C. Breithardt, Guenter Singer, Daniel E. Fox, Keith A. A. Patel, Manesh R. TI Blood pressure control and stroke or bleeding risk in anticoagulated patients with atrial fibrillation: Results from the ROCKET AF Trial SO AMERICAN HEART JOURNAL LA English DT Article ID ASPIRIN THERAPY; ISCHEMIC-STROKE; UNITED-STATES; HYPERTENSION; PREVENTION; WARFARIN; RIVAROXABAN; PREDICTORS; EVENTS; ONSET AB Background We conducted a retrospective analysis examining the association between systolic blood pressure (SBP) or hypertension bracket and stroke risk in patients with atrial fibrillation (AF). Methods The study included 14,256 anticoagulated patients in the ROCKET AF trial. Cox proportional hazards models were used to compare the risk of adverse outcomes by European Society of Cardiology hypertension bracket and screening SBP. Results In total, 90.5% of patients had hypertension (55.8% controlled, 34.6% uncontrolled). The adjusted risk of stroke or systemic embolism (SE) increased significantly for every 10-mm Hg increase in screening SBP (hazard ratio [HR] 1.07, 95% CI 1.02-1.13). There was a trend toward an increased adjusted risk of stroke or SE in patients with controlled (HR 1.22, 95% CI 0.89-1.66) and uncontrolled hypertension (HR 1.42, 95% CI 1.03-1.95) (P =.06). In contrast, the adjusted risk of major bleeding was similar between hypertensive brackets and did not vary significantly by screening SBP. The benefit of rivaroxaban versus warfarin in preventing stroke or SE was consistent among patients regardless of SBP (P interaction = .69). Conclusions In a trial of anticoagulated patients with AF, increasing screening SBP was independently associated with stroke and SE, and one-third of patients had uncontrolled hypertension. The relative effectiveness and safety of rivaroxaban versus warfarin were consistent across all levels of screening SBP. A single SBP may be an important factor in reducing the overall risk of stroke and SE in anticoagulated patients with AF. C1 [Vemulapalli, Sreekanth; Hellkamp, Anne S.; Jones, W. Schuyler; Piccini, Jonathan P.; Patel, Manesh R.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Mahaffey, Kenneth W.] Stanford Univ, Stanford, CA 94305 USA. [Becker, Richard C.] Univ Cincinnati, Cincinnati, OH USA. [Hankey, Graeme J.] Univ Western Australia, Perth, WA, Australia. [Berkowitz, Scott D.] Bayer HealthCare Pharmaceut, Whippany, NJ USA. [Nessel, Christopher C.] Janssen Res & Dev, Raritan, NJ USA. [Breithardt, Guenter] Univ Hosp Munster, Dept Cardiovasc Med, Munster, Germany. [Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Singer, Daniel E.] Harvard Med Sch, Boston, MA USA. [Fox, Keith A. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Fox, Keith A. A.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland. RP Vemulapalli, S (reprint author), Duke Univ, Med Ctr, Box 3026, Durham, NC 27710 USA. EM sreekanth.vemulapalli@duke.edu RI Hankey, Graeme /H-4968-2014 OI Hankey, Graeme /0000-0002-6044-7328 FU Janssen Research Development; Bayer HealthCare FX This work and the ROCKET AF trial were supported by Janssen Research & Development and Bayer HealthCare. The Duke Clinical Research Institute coordinated the trial, managed the database, and undertook the primary analysis independent of the sponsors. The authors had complete access to the data and were responsible for writing and submitting the manuscript for publication. NR 25 TC 0 Z9 0 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD AUG PY 2016 VL 178 BP 74 EP 84 DI 10.1016/j.ahj.2016.05.001 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DT6JK UT WOS:000381590300009 PM 27502854 ER PT J AU Decker, C Garavalia, L Garavalia, B Gialde, E Yeh, RW Spertus, J Chhatriwalla, AK AF Decker, Carole Garavalia, Linda Garavalia, Brian Gialde, Elizabeth Yeh, Robert W. Spertus, John Chhatriwalla, Adnan K. TI Understanding physician-level barriers to the use of individualized risk estimates in percutaneous coronary intervention SO AMERICAN HEART JOURNAL LA English DT Article ID BLEEDING AVOIDANCE STRATEGIES; ELEVATION MYOCARDIAL-INFARCTION; DUAL ANTIPLATELET THERAPY; COLLEGE-OF-CARDIOLOGY; DECISION-MAKING; HEALTH-CARE; PREMATURE DISCONTINUATION; QUALITATIVE RESEARCH; ATRIAL-FIBRILLATION; HEART-ASSOCIATION AB Background The foundation of precision medicine is the ability to tailor therapy based upon the expected risks and benefits of treatment for each individual patient. In a prior study, we implemented a software platform, ePRISM, to execute validated risk-stratification models for patients undergoing percutaneous coronary intervention and found substantial variability in the use of the personalized estimates to tailor care. A better understanding of physicians' perspectives about the use of individualized risk-estimates is needed to overcome barriers to their adoption. Methods In a qualitative research study, we conducted interviews, in-person or by telephone, with 27 physicians at 8 centers that used ePRISM until thematic saturation occurred. Data were coded using descriptive content analyses. Results Three major themes emerged among physicians who did not use ePRISM to support decision making: (1) "Experience versus Evidence," physicians' preference to rely upon personal experience and subjective assessments rather than objective risk estimates; (2) "Omission of Therapy," the perception that the use of risk models leads to unacceptable omission of potentially beneficial therapy; and (3) "Unnecessary Information," the opinion that information derived from risk models is not needed because physicians' decision making is already sound and they already know the information. Conclusions Barriers to the use of risk models in clinical practice include physicians' perceptions that their experience is sufficient, that models may lead to omission of therapy in patients that may benefit from therapy, and that they already provide good care. Anticipating and overcoming these barriers may improve the adoption of precision medicine. C1 [Decker, Carole; Garavalia, Brian; Gialde, Elizabeth; Spertus, John; Chhatriwalla, Adnan K.] St Lukes Mid Amer Heart Inst, 4300 Wornall Rd,Suite 2000, Kansas City, MO 64111 USA. [Decker, Carole; Garavalia, Linda; Spertus, John; Chhatriwalla, Adnan K.] Univ Missouri, Kansas City, MO 64110 USA. [Yeh, Robert W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Chhatriwalla, AK (reprint author), St Lukes Mid Amer Heart Inst, 4300 Wornall Rd,Suite 2000, Kansas City, MO 64111 USA. EM achhatriwalla@saint-lukes.org OI Garavalia, Linda/0000-0002-8156-4435 FU Health Outcomes Sciences FX The following author disclosures are provided for the previous 3 years and the immediate future: Drs Decker, L. Garavalia, B. Garavalia, Yeh, and Chhatriwalla: none; Dr Spertus: equity interest in Health Outcomes Sciences, which distributes and supports ePRISM; Ms Gialde: consulting honoraria from Health Outcomes Sciences. NR 48 TC 1 Z9 1 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD AUG PY 2016 VL 178 BP 190 EP 197 DI 10.1016/j.ahj.2016.03.027 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DT6JK UT WOS:000381590300024 PM 27502869 ER PT J AU Manian, FA Kelly, E AF Manian, Farrin A. Kelly, Erik TI Lower Extremity Acute Bacterial Skin and Soft Tissue Infection Following Total Knee Arthroplasty SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Cellulitis; Knee; Arthroplasty; Infection ID CELLULITIS; REPLACEMENT AB Background: Although total knee arthroplasty (TKA) is one of the most common orthopedic procedures, its association with subsequent acute bacterial skin and soft tissue infections (ABSSTIs) in the ipsilateral limb has not been studied. Methods: This was a retrospective study of patients with prior unilateral TKA who were diagnosed with ABSSTI 4 weeks or more postoperatively in the absence of surgical site infection. The odds of ABSSTI in the TKA limb was compared to that of the contralateral "control" limb in the same patient in the presence or absence of local predisposing factors for ABSSTI in the lower extremities (e.g., chronic venous insufficiency). results: Of 94 patients studied, 58 (62%) were women; mean age was 74.5 years. The mean body mass index was 33.1 kg/m(2). One or more local predisposing factors were present in 53 (56.4%) patients. The mean interval between TKA and ABSSTI was 65.1 months (range: 1-239 months), with cellulitis alone diagnosed in 88 (94%) patients. ABSSTI involved the TKA limb of 68 (72.3%) patients and was significantly more likely to be diagnosed in the same limb in the absence of local predisposing factors (36 of 41 patients, odds ratio = 7.2, 95% CI: 2.8-23.5); the odds of TKA limb involvement was also higher in the presence of such factors but did not quite reach statistical significance (odds ratio = 1.5, 95% CI: 0.8-2.8). Conclusions: TKA appears to predispose to ABSSTIs in the ipsilateral lower extremity often years after the procedure, particularly in the absence of other local factors. C1 [Manian, Farrin A.; Kelly, Erik] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. RP Manian, FA (reprint author), Massachusetts Gen Hosp, Dept Med, 50 Stanlford,503 B, Boston, MA 02114 USA. EM Fmanian@MGH.Harvard.edu NR 16 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 0002-9629 EI 1538-2990 J9 AM J MED SCI JI Am. J. Med. Sci. PD AUG PY 2016 VL 352 IS 2 BP 154 EP 158 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA DV1GG UT WOS:000382668000006 PM 27524213 ER PT J AU Grant, JE Leppink, EW Tsai, J Chamberlain, SR Redden, SA Curley, EE Odlaug, BL Keuthen, NJ AF Grant, Jon E. Leppink, Eric W. Tsai, Jerry Chamberlain, Samuel R. Redden, Sarah A. Curley, Erin E. Odlaug, Brian L. Keuthen, Nancy J. TI Does comorbidity matter in body-focused repetitive behavior disorders? SO ANNALS OF CLINICAL PSYCHIATRY LA English DT Article ID SKIN-PICKING DISORDER; HAIR-PULLING DISORDER; OBSESSIVE-COMPULSIVE DISORDER; STEREOTYPIC MOVEMENT-DISORDER; DYSMORPHIC DISORDER; CORTICAL THICKNESS; TRICHOTILLOMANIA; EXCORIATION; PREVALENCE AB BACKGROUND: Trichotillomania (TTM) and skin-picking disorder (SPD) have been characterized as body-focused repetitive behavior disorders (BFRBs). Because BFRBs frequently co-occur, we sought to discover the similarities and differences for individuals having both TTM and SPD as opposed to 1 of these disorders. METHODS: Participants with primary TTM (N = 421) were evaluated regarding the comorbidity of SPD, and participants with primary SPD (N = 124) were evaluated regarding the comorbidity of TTM. The effects of comorbidity overlap on demographic and clinical measures were evaluated. RESULTS: Of the 421 participants with primary TTM, 61 (14.5%) had co-occurring SPD. Of 124 participants with primary SPD, 21 (16.9%) had comorbid TTM. Participants with primary TTM and comorbid SPD had significantly more severe tricho tillomania symptoms and were more likely to have major depressive disorder than those with TTM alone. Participants with primary SPD and comorbid TTM reported significantly more severe skin-picking symptoms than those who had only SPD. CONCLUSIONS: Individuals with co-occurring TTM and SPD may have more problematic symptoms with the primary repetitive behavior. Hair pullers with comorbid SPD were more likely to have comorbid depression. Evaluating patients for multiple BFRBs may be important to assess the severity of symptoms and may have treatment implications. C1 [Grant, Jon E.; Leppink, Eric W.; Tsai, Jerry; Redden, Sarah A.] Univ Chicago, Pritzker Sch Med, Dept Psychiat & Behav Neurosci, 5841 S Maryland Ave,MC-3077, Chicago, IL 60637 USA. [Chamberlain, Samuel R.] Univ Cambridge, Cambridge & Peterborough NHS Fdn Trust CPFT, Dept Psychiat, Cambridge, England. [Curley, Erin E.; Keuthen, Nancy J.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Odlaug, Brian L.] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark. [Odlaug, Brian L.] H Lundbeck & Co AS, Valby, Denmark. RP Grant, JE (reprint author), Univ Chicago, Pritzker Sch Med, Dept Psychiat & Behav Neurosci, 5841 S Maryland Ave,MC-3077, Chicago, IL 60637 USA. EM jongrant@uchicago.edu FU Trichotillomania Learning Center; BFRB Precision Medicine Initiative FX This study was funded by the Trichotillomania Learning Center and its BFRB Precision Medicine Initiative. NR 29 TC 0 Z9 0 U1 6 U2 6 PU QUADRANT HEALTHCOM INC PI PARSIPPANY PA 7 CENTURY DRIVE, STE 302, PARSIPPANY, NJ 07054-4603 USA SN 1040-1237 EI 1547-3325 J9 ANN CLIN PSYCHIATRY JI Ann. Clin. Psychiatry PD AUG PY 2016 VL 28 IS 3 BP 175 EP 181 PG 7 WC Psychiatry SC Psychiatry GA DV1VL UT WOS:000382710100004 PM 27490833 ER PT J AU Moschovis, PP Hibberd, PL AF Moschovis, Peter P. Hibberd, Patricia L. TI Pulse oximetry: an important first step in improving health outcomes, but is of little use if there is no oxygen SO ARCHIVES OF DISEASE IN CHILDHOOD LA English DT Editorial Material ID CHILDHOOD PNEUMONIA C1 [Moschovis, Peter P.] Massachusetts Gen Hosp, Div Global Hlth, 125 Nashua St,8th Floor, Boston, MA 02114 USA. [Moschovis, Peter P.] Massachusetts Gen Hosp, Div Pulm Crit Care Med, 125 Nashua St,8th Floor, Boston, MA 02114 USA. [Hibberd, Patricia L.] Massachusetts Gen Hosp Children, Div Global Hlth, Boston, MA USA. RP Moschovis, PP (reprint author), Massachusetts Gen Hosp, Div Global Hlth, 125 Nashua St,8th Floor, Boston, MA 02114 USA.; Moschovis, PP (reprint author), Massachusetts Gen Hosp, Div Pulm Crit Care Med, 125 Nashua St,8th Floor, Boston, MA 02114 USA. EM pmoschovis@mgh.harvard.edu FU NCCIH NIH HHS [K24 AT003683]; NHLBI NIH HHS [F32 HL124951] NR 6 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 0003-9888 EI 1468-2044 J9 ARCH DIS CHILD JI Arch. Dis. Child. PD AUG PY 2016 VL 101 IS 8 BP 685 EP 685 DI 10.1136/archdischild-2015-310055 PG 1 WC Pediatrics SC Pediatrics GA DU9ZX UT WOS:000382578000001 PM 27073158 ER PT J AU Dorans, KS Wilker, EH Li, WY Rice, MB Ljungman, PL Schwartz, J Coull, BA Kloog, I Koutrakis, P D'Agostino, RB Massaro, JM Hoffmann, U O'Donnell, CJ Mittleman, MA AF Dorans, Kirsten S. Wilker, Elissa H. Li, Wenyuan Rice, Mary B. Ljungman, Petter L. Schwartz, Joel Coull, Brent A. Kloog, Itai Koutrakis, Petros D'Agostino, Ralph B., Sr. Massaro, Joseph M. Hoffmann, Udo O'Donnell, Christopher J. Mittleman, Murray A. TI Residential Proximity to Major Roads, Exposure to Fine Particulate Matter, and Coronary Artery Calcium: The Framingham Heart Study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE air pollution; atherosclerosis; coronary artery calcium; epidemiology; multidetector computed tomography ID LONG-TERM EXPOSURE; INTIMA-MEDIA THICKNESS; ACUTE MYOCARDIAL-INFARCTION; AIR-POLLUTION; CARDIOVASCULAR-DISEASE; SCIENTIFIC STATEMENT; ATHEROSCLEROSIS; ASSOCIATION; METAANALYSIS; MORTALITY AB Objective Long-term exposure to traffic and particulate matter air pollution is associated with a higher risk of cardiovascular disease, potentially via atherosclerosis promotion. Prior research on associations of traffic and particulate matter with coronary artery calcium Agatston score (CAC), an atherosclerosis correlate, has yielded inconsistent findings. Given this background, we assessed whether residential proximity to major roadway or fine particulate matter were associated with CAC in a Northeastern US study. Approach and Results We measured CAC 2 times from 2002 to 2005 and 2008 to 2011 among Framingham Offspring or Third-Generation Cohort participants. We assessed associations of residential distance to major roadway and residential fine particulate matter (2003 average; spatiotemporal model) with detectable CAC, using generalized estimating equation regression. We used linear mixed effects models to assess associations with log(e)(CAC). We also assessed associations with CAC progression. Models were adjusted for demographic variables, socioeconomic position markers, and time. Among 3399 participants, 51% had CAC measured twice. CAC was detectable in 47% of observations. At first scan, mean age was 52.2 years (standard deviation 11.7); 51% male. There were no consistent associations with detectable CAC, continuous CAC, or CAC progression. We observed heterogeneous associations of distance to major roadway with odds of detectable CAC by hypertensive status; interpretation of these findings is questionable. Conclusions Our findings add to prior work and support evidence against strong associations of traffic or fine particulate matter with the presence, extent, or progression of CAC in a region with relatively low levels of and little variation in fine particulate matter. C1 [Dorans, Kirsten S.; Wilker, Elissa H.; Li, Wenyuan; Schwartz, Joel; Mittleman, Murray A.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Wilker, Elissa H.; Schwartz, Joel; Koutrakis, Petros] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Coull, Brent A.] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Dorans, Kirsten S.; Wilker, Elissa H.; Li, Wenyuan; Rice, Mary B.; Ljungman, Petter L.; Mittleman, Murray A.] Harvard Med Sch, Cardiovasc Epidemiol Res Unit, Dept Cardiol, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Rice, Mary B.] Harvard Med Sch, Div Pulm Crit Care & Sleep Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Hoffmann, Udo] Harvard Med Sch, Cardiac MR PET CT Program, Dept Radiol, Massachusetts Gen Hosp, Boston, MA USA. [O'Donnell, Christopher J.] Harvard Med Sch, Cardiovasc Med, Brigham & Womens Hosp, Boston, MA USA. [Ljungman, Petter L.] Karolinska Inst, Inst Environm Med, Environm Epidemiol Unit, Stockholm, Sweden. [Kloog, Itai] Ben Gurion Univ Negev, Dept Geog & Environm Dev, Beer Sheva, Israel. [D'Agostino, Ralph B., Sr.; Massaro, Joseph M.; O'Donnell, Christopher J.] NHLBI, Framingham, MA USA. [D'Agostino, Ralph B., Sr.; Massaro, Joseph M.; O'Donnell, Christopher J.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [O'Donnell, Christopher J.] Boston Vet Adm Hlth Syst, Cardiol Sect, Dept Med, Boston, MA USA. RP Mittleman, MA (reprint author), Harvard TH Chan Sch Publ Hlth, 677 Huntington Ave,Suite 505, Boston, MA 02215 USA. EM mmittlem@hsph.harvard.edu OI Dorans, Kirsten/0000-0002-3182-5633 FU National Institutes of Health (NIH) [NHLBI T32 HL007575, NIEHS R00 ES022243, K23ES026204]; US Environmental Protection Agency [RD-83479801, RD-83587201]; NHLBI's Framingham Heart Study [HHSN268201500001I] FX This work was supported by the National Institutes of Health (NIH; NHLBI T32 HL007575; NIEHS R00 ES022243, K23ES026204). This publication was made possible by US Environmental Protection Agency grants RD-83479801 and RD-83587201. Its contents are solely the responsibility of the grantee and do not necessarily represent the official views of the US Environmental Protection Agency. Further, US Environmental Protection Agency does not endorse the purchase of any commercial products or services mentioned in the publication. From the Framingham Heart Study of the NHLBI of the NIH and Boston University School of Medicine; this work was supported by the NHLBI's Framingham Heart Study (Contract No. HHSN268201500001I). The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the NHLBI, the NIH, or the US Department of Health and Human Services. NR 34 TC 3 Z9 3 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD AUG PY 2016 VL 36 IS 8 BP 1679 EP 1685 DI 10.1161/ATVBAHA.116.307141 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA DT4TM UT WOS:000381474000025 PM 27312220 ER PT J AU Januzzi, JL Lyass, A Liu, YY Gaggin, H Trebnick, A Maisel, AS D'Agostino, RB Wang, TJ Massaro, J Vasan, RS AF Januzzi, James L., Jr. Lyass, Asya Liu, Yuyin Gaggin, Hanna Trebnick, April Maisel, Alan S. D'Agostino, Ralph B., Sr. Wang, Thomas J. Massaro, Joseph Vasan, Ramachandran S. TI Circulating Proneurotensin Concentrations and Cardiovascular Disease Events in the Community: The Framingham Heart Study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE diabetes mellitus; myocardial infarction; nucleotides; risk factors; stroke ID NEUROTENSIN; BIOMARKERS; PEPTIDE; SORT1 AB Objective Neurotensin is a peptide whose receptor (sortilin receptor 1) is linked to cardiovascular disease (CVD) development. We hypothesized concentrations of proneurotensin (stable profragment of neurotensin) would predict incident cardiovascular events in community-based subjects. Approach and Results Blood samples from 3439 participants in the Framingham Heart Study (FHS) Offspring cohort (mean age 59.2 years, 47.1% male) were tested for proneurotensin. Primary outcome of interest was incident hard CVD (myocardial infarction, stroke, and cardiovascular death); interaction between proneurotensin concentration with sex, low-density lipoprotein concentrations, and sortilin receptor 1 single-nucleotide polymorphisms was sought. At baseline, those in the highest log-proneurotensin quartile were younger and heavier (P<0.001); across proneurotensin quartiles, more prevalent hard CVD (from 3% to 7%; P<0.001) and diabetes mellitus (from 6% to 14%; P<0.001) were present. In age- and sex-adjusted models, log-proneurotensin concentrations predicted incident hard CVD (hazard ratio [HR], 1.24 per SD change in log-proneurotensin; 95% confidence intervals [CIs], 1.11-1.39; P<0.001), a finding that remained on adjustment for standard CVD risk factors (HR, 1.13; 95% CI, 1.01-1.27; P=0.03). Elevated log-proneurotensin concentrations were associated with shorter time to first event (P=0.02). We found no effect modification by sex, low-density lipoprotein concentration, or sortilin receptor 1 single-nucleotide polymorphisms. Concentrations of proneurotensin were modestly associated with left ventricular mass and coronary artery calcium in these subjects. Conclusions Higher concentrations of proneurotensin are associated with a greater risk of incident cardiovascular events in the community. This association did not vary according to sex, baseline low-density lipoprotein, or sortilin receptor 1 genotype. C1 [Januzzi, James L., Jr.; Lyass, Asya; Gaggin, Hanna; D'Agostino, Ralph B., Sr.; Wang, Thomas J.; Massaro, Joseph; Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Januzzi, James L., Jr.; Gaggin, Hanna] Massachusetts Gen Hosp, Div Cardiol, Yawkey 5B,55 Fruit St, Boston, MA 02114 USA. [Januzzi, James L., Jr.; Gaggin, Hanna; Trebnick, April] Harvard Clin Res Inst, Dept Cardiometab Trials, Boston, MA USA. [Lyass, Asya; Liu, Yuyin; D'Agostino, Ralph B., Sr.; Massaro, Joseph] Harvard Clin Res Inst, Dept Biostat, Boston, MA USA. [Lyass, Asya; D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Liu, Yuyin; Massaro, Joseph] Boston Univ, Med Ctr, Dept Biostat, Boston, MA 02215 USA. [Vasan, Ramachandran S.] Boston Univ, Med Ctr, Dept Preventat Med, Boston, MA 02215 USA. [Maisel, Alan S.] Vet Affairs Med Ctr, Heart Failure Sect, San Diego, CA 92161 USA. [Wang, Thomas J.] Vanderbilt Univ Sch Med, Div Cardiol, Nashville, TN USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey 5B,55 Fruit St, Boston, MA 02114 USA. EM jjanuzzi@mgh.harvard.edu FU Hutter Family Professorship in the Field of Cardiology; DeSanctis Endowed Clinical Scholar in Medicine Fund; Clark Fund for Cardiac Research Innovation; National Heart Lung and Blood Institute [N01-HC-25195, HHSN268201500001I] FX Dr Januzzi is supported, in part, by the Hutter Family Professorship in the Field of Cardiology, as well as the DeSanctis Endowed Clinical Scholar in Medicine Fund. Dr Gaggin is supported. in part, by the Clark Fund for Cardiac Research Innovation. Dr Vasan is supported, in part, by National Heart Lung and Blood Institute contracts N01-HC-25195 and HHSN268201500001I. NR 14 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 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD AUG PY 2016 VL 36 IS 8 BP 1692 EP 1697 DI 10.1161/ATVBAHA.116.307847 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA DT4TM UT WOS:000381474000027 PM 27312221 ER PT J AU Perez, DL Torous, J Stern, AP Padmanabhan, JL Keshavan, MS AF Perez, David L. Torous, John Stern, Adam P. Padmanabhan, Jaya L. Keshavan, Matcheri S. TI Response to "Tandon et al. Psychiatry is a clinical neuroscience, but how do we move the field'' SO ASIAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID NETWORK; FUTURE C1 [Perez, David L.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. [Perez, David L.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. [Torous, John] Harvard Longwood Psychiat Residency Training Prog, Boston, MA USA. [Torous, John] Harvard Med Sch, Brigham & Womens Hosp, Dept Psychiat, Boston, MA USA. [Torous, John; Stern, Adam P.; Padmanabhan, Jaya L.; Keshavan, Matcheri S.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA USA. [Stern, Adam P.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Boston, MA USA. [Padmanabhan, Jaya L.] McLean Hosp, Dept Behav Neurol & Neuropsychiat, Belmont, MA USA. RP Perez, DL (reprint author), Massachusetts Gen Hosp, Dept Neurol, 149 13th St, Charlestown, MA 02129 USA.; Perez, DL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 149 13th St, Charlestown, MA 02129 USA. EM dlperez@partners.org OI Padmanabhan, Jaya/0000-0003-3958-5424 NR 10 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1876-2018 EI 1876-2026 J9 ASIAN J PSYCHIATR JI Asian J. Psychiatr. PD AUG PY 2016 VL 22 BP 15 EP 16 DI 10.1016/j.ajp.2016.03.005 PG 2 WC Psychiatry SC Psychiatry GA DU1WQ UT WOS:000382001400004 PM 27520888 ER PT J AU Chandra, RM Arora, L Mehta, UM Asnaani, A Radhakrishnan, R AF Chandra, Rohit M. Arora, Lily Mehta, Urvakhsh M. Asnaani, Anu Radhakrishnan, Rajiv TI Asian Indians in America: The influence of values and culture on mental health SO ASIAN JOURNAL OF PSYCHIATRY LA English DT Review DE Asian Indians; Culture; Values; Mental health; Cross-cultural ID UNITED-STATES; ALCOHOL-USE; 1ST-EPISODE PSYCHOSIS; PREVALENCE RATES; USE DISORDERS; SCHIZOPHRENIA; SUICIDE; WOMEN; DEPRESSION; SYMPTOMS AB Asian Indians represent a significant portion of the largest growing race of Asians in the past decade in the United States. This selective review examines major cultural themes related to first-and second-generation Asian Indians living in the United States as they impact psychological and psychiatric dysfunction in this population. Specifically, we review the impact of Asian Indian culture on mental health, discuss the impact of acculturation and ethnic identity development on the mental health of Indian-Americans, and focus on typical mental health problems of Asian Indian adolescents, women and elderly in America. Finally, we provide a brief overview of empirically-supported treatment approaches and cultural considerations for additional treatments relevant to this population. This review is intended to provide an important foundation for more systematic empirically-driven investigation into better understanding how Asian Indian cultural themes impact mental health for Indian-Americans, and how to develop effective treatments for these issues in this cultural group. (C) 2015 Elsevier B.V. All rights reserved. C1 [Chandra, Rohit M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Arora, Lily] Rutgers State Univ, New Jersey Med Sch, Newark, NJ USA. [Mehta, Urvakhsh M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Mehta, Urvakhsh M.] Natl Inst Mental Hlth & Neurosci NIMHANS, Bangalore, Karnataka, India. [Asnaani, Anu] Univ Penn, Dept Psychiat, Ctr Treatment & Study Anxiety, 3535 Market St,Suite 600 North, Philadelphia, PA 19104 USA. [Radhakrishnan, Rajiv] Yale Univ, Sch Med, New Haven, CT USA. RP Asnaani, A (reprint author), Univ Penn, Dept Psychiat, Ctr Treatment & Study Anxiety, 3535 Market St,Suite 600 North, Philadelphia, PA 19104 USA. EM aasnaani@mail.med.upenn.edu NR 81 TC 0 Z9 0 U1 13 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1876-2018 EI 1876-2026 J9 ASIAN J PSYCHIATR JI Asian J. Psychiatr. PD AUG PY 2016 VL 22 BP 202 EP 209 DI 10.1016/j.ajp.2015.09.011 PG 8 WC Psychiatry SC Psychiatry GA DU1WQ UT WOS:000382001400045 PM 26442987 ER PT J AU Anderson, L Razavi, M Skates, S Anderson, NG Pearson, TW AF Anderson, Leigh Razavi, Morteza Skates, Steven Anderson, Norman G. Pearson, Terry W. TI Squeezing more value from the analytes we have: personal baselines for multiple analytes in serial DBS SO BIOANALYSIS LA English DT Editorial Material DE DBS; MS; panels; personalized C1 [Anderson, Leigh; Razavi, Morteza; Pearson, Terry W.] SISCAPA Assay Technol, Washington, DC USA. [Anderson, Leigh; Razavi, Morteza; Pearson, Terry W.] SISCAPA Assay Technol, Victoria, BC, Canada. [Skates, Steven] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Skates, Steven] Harvard Med Sch, Boston, MA USA. [Anderson, Norman G.] Viral Def Fdn, Rockville, MD USA. RP Anderson, L (reprint author), SISCAPA Assay Technol, Washington, DC USA.; Anderson, L (reprint author), SISCAPA Assay Technol, Victoria, BC, Canada. EM leighanderson@siscapa.com NR 12 TC 1 Z9 1 U1 0 U2 0 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 EI 1757-6199 J9 BIOANALYSIS JI Bioanalysis PD AUG PY 2016 VL 8 IS 15 BP 1539 EP 1542 DI 10.4155/bio-2016-0088 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA DS8LR UT WOS:000381035400002 PM 27277878 ER PT J AU Thomas, EG Toufaily, MH Westgate, MN Hunt, AT Lin, AE Holmes, LB AF Thomas, Emma G. Toufaily, M. Hassan Westgate, Marie-Noel Hunt, Anne-Therese Lin, Angela E. Holmes, Lewis B. TI Impact of elective termination on the occurrence of severe birth defects identified in a hospital-based active malformations surveillance program (1999 to 2002) SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article DE malformations surveillance; elective termination; severity of malformations; occurrence of malformations ID PRENATAL-DIAGNOSIS; NEWBORN-INFANTS; CLASSIFICATION; PREVALENCE; TRENDS AB BackgroundThe number of affected infants and the types of malformations identified by a malformation surveillance programs can be impacted if elective terminations for malformations are not included. MethodsThe occurrence of malformations in all newborn infants was determined in a daily review of the findings in the pediatricians' examinations and those of all consultants. In addition, the findings in autopsies of all elective terminations were reviewed to identify all fetuses with structural abnormalities. A severity scale was used to subdivide the malformations. To establish the impact of elective termination, the malformed infants identified in the Active Malformations Surveillance Program at Brigham and Women's Hospital in Boston were analyzed for the 2 years before and after the hospital decreased significantly the number of elective terminations temporarily (1999-2000 vs. 2001-2002). The effect on the number of malformations identified at birth, as well as malformations of greater severity, was determined. ResultsThe number of terminated fetuses with malformations decreased dramatically after termination services were interrupted (p<0.0001). There were no differences in the prevalence rates of all malformations in the 2 years before and after the change in access to elective terminations. However, there were significant decreases in the number of infants identified with lethal/life-limiting and severe/handicapping malformations. ConclusionIn the surveillance for malformations among newborn infants, the inclusion of malformed fetuses from elective terminations had a significant effect on the number of infants with the more severe malformations identified. Birth Defects Research (Part A) 106:659-666, 2016. (c) 2016 Wiley Periodicals, Inc. C1 [Thomas, Emma G.; Toufaily, M. Hassan; Westgate, Marie-Noel; Lin, Angela E.; Holmes, Lewis B.] Harvard Med Sch, Brigham & Womens Hosp, Dept Pediat Newborn Med, Act Malformat Surveillance Program, Boston, MA USA. [Thomas, Emma G.; Toufaily, M. Hassan; Westgate, Marie-Noel; Lin, Angela E.; Holmes, Lewis B.] Harvard Med Sch, MassGen Hosp Children, Med Genet Unit, Boston, MA USA. [Hunt, Anne-Therese] Hunt Consulting Associates, Thetford Ctr, VT USA. RP Toufaily, MH (reprint author), MassGen Hosp Children, Med Genet Unit, 175 Cambridge St,5th Floor, Boston, MA 02114 USA. EM htoufaily@mgh.harvard.edu NR 15 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD AUG PY 2016 VL 106 IS 8 BP 659 EP 666 DI 10.1002/bdra.23510 PG 8 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA DV3RC UT WOS:000382839700003 PM 27116560 ER PT J AU Ramachandran, J Santo, L Siu, KT Panaroni, C Raje, N AF Ramachandran, J. Santo, L. Siu, K. T. Panaroni, C. Raje, N. TI Pim2 is important for regulating DNA damage response in multiple myeloma cells SO BLOOD CANCER JOURNAL LA English DT Article ID SERINE/THREONINE KINASE PIM-2; DOXORUBICIN; INHIBITION; RADIATION; SURVIVAL; THERAPY; CANCERS; GROWTH; TUMOR AB Pan proviral integrations of Moloney virus (PIM) inhibition in multiple myeloma (MM) results in reduced cell viability in tested human-derived MM cell lines and reduces tumor burden in xenograft mouse models, making PIMs important therapeutic targets for the disease. PIM kinase inhibitors are currently being tested clinically in MM. We sought to elucidate the role of the various PIMs in MM. Our data demonstrate that Pim2 has a significant role in MM cell cytotoxicity. Our data provide evidence for a novel role for Pim2 in the regulation of the DNA damage response (DDR). Knockdown of Pim2 upregulates several downstream DDR markers, mimicking the effects of doxorubicin (Dox) treatment of MM cells, and suggesting a role for the kinase as a negative regulator of this pathway. Dox-induced DNA damage results in a decrease in Pim2 levels, placing the kinase directly downstream of the site of Dox-DNA binding. Overexpression of Pim2 confers a slight survival advantage against Dox through antiapoptotic activity, further underscoring its relevance in the DDR pathway. These data provide insights into a novel mechanism of PIM kinase activity and provide the framework for designing therapeutic approaches in MM. C1 [Ramachandran, J.; Santo, L.; Siu, K. T.; Panaroni, C.; Raje, N.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, POB 216,55 Fruit St, Boston, MA 02114 USA. RP Raje, N (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, POB 216,55 Fruit St, Boston, MA 02114 USA. EM nraje@mgh.harvard.edu FU internal Multiple Myeloma Research Fund at MGH FX This work was supported by an internal Multiple Myeloma Research Fund at MGH. NR 20 TC 1 Z9 1 U1 1 U2 1 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 AUG PY 2016 VL 6 AR e462 DI 10.1038/bcj.2016.73 PG 7 WC Oncology SC Oncology GA DU3MG UT WOS:000382114300008 PM 27564460 ER PT J AU Wise, R Anzueto, A Dahl, R Dusser, D Calverley, P AF Wise, Robert Anzueto, Antonio Dahl, Ronald Dusser, Daniel Calverley, Peter TI Tiotropium safety in 'real-world' populations SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Letter ID OBSTRUCTIVE PULMONARY-DISEASE; TIOSPIR TRIAL; RESPIMAT; COPD C1 [Wise, Robert] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. [Anzueto, Antonio] Univ Texas San Antonio, San Antonio, TX USA. [Anzueto, Antonio] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Dahl, Ronald] Odense Univ Hosp, Odense C, Denmark. [Dusser, Daniel] Univ Paris 05, Sorbonne Paris Cite, Hop Cochin, AP HP,Serv Pneumol, Paris, France. [Calverley, Peter] Univ Liverpool, Inst Ageing & Chron Dis, Liverpool, Merseyside, England. RP Wise, R (reprint author), Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. EM rwise@jhmi.edu NR 10 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0306-5251 EI 1365-2125 J9 BRIT J CLIN PHARMACO JI Br. J. Clin. Pharmacol. PD AUG PY 2016 VL 82 IS 2 BP 562 EP 563 DI 10.1111/bcp.12972 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DU9AV UT WOS:000382509500025 PM 27197835 ER PT J AU Ardeljan, D Taylor, MS Burns, KH Boeke, JD Espey, MG Woodhouse, EC Howcroft, TK AF Ardeljan, Daniel Taylor, Martin S. Burns, Kathleen H. Boeke, Jef D. Espey, Michael Graham Woodhouse, Elisa C. Howcroft, Thomas Kevin TI Meeting Report: The Role of the Mobilome in Cancer SO CANCER RESEARCH LA English DT Editorial Material ID SOMATIC L1 RETROTRANSPOSITION; TRANSPOSABLE ELEMENTS; HUMAN BRAIN; EXPRESSION; MUTAGENESIS; DROSOPHILA; MOSAICISM; EVOLUTION; CARCINOMA; GENOMES AB Approximately half of the human genome consists of repetitive sequence attributed to the activities of mobile DNAs, including DNA transposons, RNA transposons, and endogenous retroviruses. Of these, only long interspersed elements (LINE-1 or L1) and sequences copied by LINE-1 remain mobile in our species today. Although cells restrict L1 activity by both transcriptional and posttranscriptional mechanisms, L1 derepression occurs in developmental and pathologic contexts, including many types of cancers. However, we have limited knowledge of the extent and consequences of L1 expression in premalignancies and cancer. Participants in this NIH strategic workshop considered key questions to enhance our understanding of mechanisms and roles the mobilome may play in cancer biology. (C) 2016 AACR. C1 [Ardeljan, Daniel; Burns, Kathleen H.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Ardeljan, Daniel] Johns Hopkins Univ, Sch Med, Med Scientist Training Program, Baltimore, MD USA. [Taylor, Martin S.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Burns, Kathleen H.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Boeke, Jef D.] NYU, Langone Med Ctr, Inst Syst Genet, New York, NY USA. [Espey, Michael Graham; Woodhouse, Elisa C.; Howcroft, Thomas Kevin] NCI, Div Canc Biol, NIH, Rockville, MD USA. RP Woodhouse, EC (reprint author), NCI, Tumor Biol & Metastasis Branch, 9609 Med Ctr Dr,Room 6W416, Bethesda, MD 20892 USA. EM woodhousee@mail.nih.gov OI Taylor, Martin/0000-0001-5824-142X FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [R01 CA163705]; NIGMS NIH HHS [T32 GM007309, P50 GM107632] NR 29 TC 0 Z9 0 U1 2 U2 2 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 AUG 1 PY 2016 VL 76 IS 15 BP 4316 EP 4319 DI 10.1158/0008-5472.CAN-15-3421 PG 4 WC Oncology SC Oncology GA DU6AO UT WOS:000382295300004 PM 27527733 ER PT J AU Jiang, X Bugno, J Hu, C Yang, Y Herold, T Qi, J Chen, P Gurbuxani, S Arnovitz, S Strong, J Ferchen, K Ulrich, B Weng, HY Wang, YG Huang, H Li, SL Neilly, MB Larson, RA Le Beau, MM Bohlander, SK Jin, J Li, ZJ Bradner, JE Hong, S Chen, JJ AF Jiang, Xi Bugno, Jason Hu, Chao Yang, Yang Herold, Tobias Qi, Jun Chen, Ping Gurbuxani, Sandeep Arnovitz, Stephen Strong, Jennifer Ferchen, Kyle Ulrich, Bryan Weng, Hengyou Wang, Yungui Huang, Hao Li, Shenglai Neilly, Mary Beth Larson, Richard A. Le Beau, Michelle M. Bohlander, Stefan K. Jin, Jie Li, Zejuan Bradner, James E. Hong, Seungpyo Chen, Jianjun TI Eradication of Acute Myeloid Leukemia with FLT3 Ligand-Targeted miR-150 Nanoparticles SO CANCER RESEARCH LA English DT Article ID SUPPORTED LIPID-BILAYERS; POLY(AMIDOAMINE) DENDRIMERS; THERAPEUTIC TARGET; NORMAL CYTOGENETICS; MLL TRANSLOCATIONS; PAMAM DENDRIMERS; SIRNA DELIVERY; HOLE FORMATION; CANCER CELLS; GROUP-B AB Acute myeloid leukemia (AML) is a common and fatal form of hematopoietic malignancy. Overexpression and/or mutations of FLT3 have been shown to occur in the majority of cases of AML. Our analysis of a large-scale AML patient cohort (N = 562) indicates that FLT3 is particularly highly expressed in some subtypes of AML, such as AML with t(11q23)/MLL-rearrangements or FLT3-ITD. Such AML subtypes are known to be associated with unfavorable prognosis. To treat FLT3-overexpressing AML, we developed a novel targeted nanoparticle system: FLT3 ligand (FLT3L)-conjugated G7 poly(amidoamine) (PAMAM) nanosized dendriplex encapsulating miR-150, a pivotal tumor suppressor and negative regulator of FLT3. We show that the FLT3L-guided miR-150 nanoparticles selectively and efficiently target FLT3-overexpressing AML cells and significantly inhibit viability/growth and promote apoptosis of the AML cells. Our proof-of-concept animal model studies demonstrate that the FLT3L-guided miR-150 nanoparticles tend to concentrate in bone marrow, and significantly inhibit progression of FLT3-overexpressing AML in vivo, while exhibiting no obvious side effects on normal hematopoiesis. Collectively, we have developed a novel targeted therapeutic strategy, using FLT3L-guided miR-150-based nanoparticles, to treat FLT3-overexpressing AML with high efficacy and minimal side effects. (C) 2016 AACR. C1 [Jiang, Xi; Hu, Chao; Strong, Jennifer; Ferchen, Kyle; Weng, Hengyou; Wang, Yungui; Chen, Jianjun] Univ Cincinnati, Dept Canc Biol, Cincinnati, OH USA. [Jiang, Xi; Hu, Chao; Chen, Ping; Arnovitz, Stephen; Ulrich, Bryan; Weng, Hengyou; Wang, Yungui; Huang, Hao; Li, Shenglai; Neilly, Mary Beth; Larson, Richard A.; Le Beau, Michelle M.; Li, Zejuan; Chen, Jianjun] Univ Chicago, Dept Med, Sect Hematol Oncol, 5841 S Maryland Ave, Chicago, IL 60637 USA. [Bugno, Jason; Yang, Yang; Hong, Seungpyo] Univ Illinois, Coll Pharm, Dept Biopharmaceut Sci, Chicago, IL USA. [Hu, Chao; Wang, Yungui; Jin, Jie] Zhejiang Univ, Affiliated Hosp 1, Dept Hematol, Hangzhou, Zhejiang, Peoples R China. [Hu, Chao; Wang, Yungui; Jin, Jie] Zhejiang Univ, Key Lab Hematopoiet Malignancy, Hangzhou, Zhejiang, Peoples R China. [Herold, Tobias] Univ Munich, Univ Hosp Grosshadern, Dept Internal Med 3, Munich, Germany. [Qi, Jun; Bradner, James E.] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Gurbuxani, Sandeep] Univ Chicago, Dept Pathol, 5841 S Maryland Ave, Chicago, IL 60637 USA. [Bohlander, Stefan K.] Univ Auckland, Dept Mol Med & Pathol, Auckland, New Zealand. [Hong, Seungpyo] Yonsei Univ, Underwood Int Coll, Div Integrated Sci & Engn, Inchon, South Korea. RP Jiang, X (reprint author), Univ Cincinnati, Dept Canc Biol, Cincinnati, OH USA.; Jiang, X (reprint author), Univ Chicago, Dept Med, Sect Hematol Oncol, 5841 S Maryland Ave, Chicago, IL 60637 USA.; Hong, S (reprint author), Univ Illinois, Coll Pharm, Dept Biopharmaceut Sci, Chicago, IL USA.; Hong, S (reprint author), Yonsei Univ, Underwood Int Coll, Div Integrated Sci & Engn, Inchon, South Korea.; Chen, JJ (reprint author), Univ Cincinnati, 3125 Eden Ave,Room 3316, Cincinnati, OH 45219 USA. EM jiangx4@uc.edu; sphong@uic.edu; chen3jj@uc.edu OI Larson, Richard/0000-0001-9168-3203 FU NCI NIH HHS [R01 CA182528, R01 CA127277, R01 CA178454] NR 46 TC 0 Z9 0 U1 7 U2 7 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 AUG 1 PY 2016 VL 76 IS 15 BP 4470 EP 4480 DI 10.1158/0008-5472.CAN-15-2949 PG 11 WC Oncology SC Oncology GA DU6AO UT WOS:000382295300017 PM 27280396 ER PT J AU Oddo, D Sennott, EM Barault, L Valtorta, E Arena, S Cassingena, A Filiciotto, G Marzolla, G Elez, E van Geel, RMJM Bartolini, A Crisafulli, G Boscaro, V Godfrey, JT Buscarino, M Cancelliere, C Linnebacher, M Corti, G Truini, M Siravegna, G Grasselli, J Gallicchio, M Bernards, R Schellens, JHM Tabernero, J Engelman, JA Sartore-Bianchi, A Bardelli, A Siena, S Corcoran, RB Di Nicolantonio, F AF Oddo, Daniele Sennott, Erin M. Barault, Ludovic Valtorta, Emanuele Arena, Sabrina Cassingena, Andrea Filiciotto, Genny Marzolla, Giulia Elez, Elena van Geel, Robin M. J. M. Bartolini, Alice Crisafulli, Giovanni Boscaro, Valentina Godfrey, Jason T. Buscarino, Michela Cancelliere, Carlotta Linnebacher, Michael Corti, Giorgio Truini, Mauro Siravegna, Giulia Grasselli, Julieta Gallicchio, Margherita Bernards, Rene Schellens, Jan H. M. Tabernero, Josep Engelman, Jeffrey A. Sartore-Bianchi, Andrea Bardelli, Alberto Siena, Salvatore Corcoran, Ryan B. Di Nicolantonio, Federica TI Molecular Landscape of Acquired Resistance to Targeted Therapy Combinations in BRAF-Mutant Colorectal Cancer SO CANCER RESEARCH LA English DT Article ID MUTATIONS CONFER RESISTANCE; RAF INHIBITOR RESISTANCE; MEK INHIBITORS; BRAF(V600E) INHIBITION; METASTATIC MELANOMA; COLON-CANCER; EGFR; AMPLIFICATION; VEMURAFENIB; CETUXIMAB AB Although recent clinical trials of BRAF inhibitor combinations have demonstrated improved efficacy in BRAF-mutant colorectal cancer, emergence of acquired resistance limits clinical benefit. Here, we undertook a comprehensive effort to define mechanisms underlying drug resistance with the goal of guiding development of therapeutic strategies to overcome this limitation. We generated a broad panel of BRAF-mutant resistant cell line models across seven different clinically relevant drug combinations. Combinatorial drug treatments were able to abrogate ERK1/2 phosphorylation in parental-sensitive cells, but not in their resistant counterparts, indicating that resistant cells escaped drug treatments through one or more mechanisms leading to biochemical reactivation of the MAPK signaling pathway. Genotyping of resistant cells identified gene amplification of EGFR, KRAS, and mutant BRAF, as well as acquired mutations in KRAS, EGFR, and MAP2K1. These mechanisms were clinically relevant, as we identified emergence of a KRAS G12C mutation and increase of mutant BRAF V600E allele frequency in the circulating tumor DNA of a patient at relapse from combined treatment with BRAF and MEK inhibitors. To identify therapeutic combinations capable of overcoming drug resistance, we performed a systematic assessment of candidate therapies across the panel of resistant cell lines. Independent of the molecular alteration acquired upon drug pressure, most resistant cells retained sensitivity to vertical MAPK pathway suppression when combinations of ERK, BRAF, and EGFR inhibitors were applied. These therapeutic combinations represent promising strategies for future clinical trials in BRAF-mutant colorectal cancer. (C) 2016 AACR. C1 [Oddo, Daniele; Barault, Ludovic; Arena, Sabrina; Filiciotto, Genny; Marzolla, Giulia; Siravegna, Giulia; Bardelli, Alberto; Di Nicolantonio, Federica] Univ Torino, Dept Oncol, Str Prov 142,Km 3-95, I-10060 Turin, Italy. [Oddo, Daniele; Barault, Ludovic; Arena, Sabrina; Filiciotto, Genny; Marzolla, Giulia; Bartolini, Alice; Crisafulli, Giovanni; Buscarino, Michela; Cancelliere, Carlotta; Corti, Giorgio; Siravegna, Giulia; Bardelli, Alberto; Di Nicolantonio, Federica] IRCCS, Candiolo Canc Inst FPO, Turin, Italy. [Sennott, Erin M.; Godfrey, Jason T.; Engelman, Jeffrey A.; Corcoran, Ryan B.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Valtorta, Emanuele; Cassingena, Andrea; Truini, Mauro; Sartore-Bianchi, Andrea; Siena, Salvatore] Grande Osped Metropolitano Niguarda, Niguarda Canc Ctr, Milan, Italy. [Elez, Elena; Grasselli, Julieta; Tabernero, Josep] Vall dHebron Univ Hosp, Barcelona, Spain. [Elez, Elena; Grasselli, Julieta; Tabernero, Josep] Univ Autonoma Barcelona, Inst Oncol VHIO, Barcelona, Spain. [van Geel, Robin M. J. M.; Bernards, Rene; Schellens, Jan H. M.] Netherlands Canc Inst, Amsterdam, Netherlands. [Boscaro, Valentina; Gallicchio, Margherita] Univ Turin, Dept Drug Sci & Technol, Turin, Italy. [Linnebacher, Michael] Univ Rostock, Div Mol Oncol & Immunotherapy, Dept Gen Surg, Rostock, Germany. [Siravegna, Giulia] FIRC Inst Mol Oncol IFOM, Milan, Italy. [Engelman, Jeffrey A.; Corcoran, Ryan B.] Harvard Med Sch, Dept Med, Boston, MA USA. [Siena, Salvatore] Univ Milan, Dept Oncol, Milan, Italy. RP Di Nicolantonio, F (reprint author), Univ Torino, Dept Oncol, Str Prov 142,Km 3-95, I-10060 Turin, Italy. EM federica.dinicolantonio@unito.it RI Di Nicolantonio, Federica/A-2503-2011; OI Di Nicolantonio, Federica/0000-0001-9618-2010; Bernards, Rene/0000-0001-8677-3423; ARENA, Sabrina/0000-0002-1318-2494 FU NCI NIH HHS [K08 CA166510, P50 CA127003] NR 49 TC 6 Z9 6 U1 11 U2 12 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 AUG 1 PY 2016 VL 76 IS 15 BP 4504 EP 4515 DI 10.1158/0008-5472.CAN-16-0396 PG 12 WC Oncology SC Oncology GA DU6AO UT WOS:000382295300020 PM 27312529 ER PT J AU Feldman, AZ Brown, FM AF Feldman, Anna Z. Brown, Florence M. TI Management of Type 1 Diabetes in Pregnancy SO CURRENT DIABETES REPORTS LA English DT Review DE Type 1 diabetes; Pregnancy; Preconception; Postpartum ID RANDOMIZED-CONTROLLED-TRIAL; SUBCUTANEOUS INSULIN INFUSION; AMERICAN THYROID ASSOCIATION; FETAL LUNG MATURATION; METABOLIC-CONTROL; CONGENITAL-MALFORMATIONS; SEVERE HYPOGLYCEMIA; PRECONCEPTION CARE; PERINATAL OUTCOMES; GLUCOSE-TOLERANCE AB Women with type 1 diabetes (T1DM) have unique needs during the preconception, pregnancy, and postpartum periods. Preconception counseling is essential for women with T1DM to minimize pregnancy risks. The goals of preconception care should be tight glycemic control with a hemoglobin A1c (A1C) < 7 % and as close to 6 % as possible, without significant hypoglycemia. This will lower risks of congenital malformations, preeclampsia, and perinatal mortality. The safety of medications should be assessed prior to conception. Optimal control of retinopathy, hypertension, and nephropathy should be achieved. During pregnancy, the goal A1C is near-normal at < 6 %, without excessive hypoglycemia. There is no clear evidence that continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI) is superior in achieving the desired tight glycemic control of T1DM during pregnancy. Data regarding continuous glucose monitoring (CGM) in pregnant women with T1DM is conflicting regarding improved glycemic control. However, a recent CGM study does provide some distinct patterns of glucose levels associated with large for gestational age infants. Frequent eye exams during pregnancy are essential due to risk of progression of retinopathy during pregnancy. Chronic hypertension treatment goals are systolic blood pressure 110129 mmHg and diastolic blood pressure 65-79 mmHg. Labor and delivery target plasma glucose levels are 80110 mg/dl, and an insulin drip is recommended to achieve these targets during active labor. Postpartum, insulin doses must be reduced and glucoses closely monitored in women with T1DM because of the enhanced insulin sensitivity after delivery. Breastfeeding is recommended and should be highly encouraged due to maternal benefits including increased insulin sensitivity and weight loss and infant and childhood benefits including reduced prevalence of overweight. In this article, we discuss the care of pregnant patients with T1DM. C1 [Feldman, Anna Z.; Brown, Florence M.] Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02115 USA. RP Brown, FM (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02115 USA. EM florence.brown@joslin.harvard.edu NR 141 TC 0 Z9 0 U1 4 U2 5 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 EI 1539-0829 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD AUG PY 2016 VL 16 IS 8 AR 76 DI 10.1007/s11892-016-0765-z PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DU1UR UT WOS:000381995900010 PM 27337958 ER PT J AU Gonzalez-Franquesa, A Burkart, AM Isganaitis, E Patti, ME AF Gonzalez-Franquesa, Alba Burkart, Alison M. Isganaitis, Elvira Patti, Mary-Elizabeth TI What Have Metabolomics Approaches Taught Us About Type 2 Diabetes? SO CURRENT DIABETES REPORTS LA English DT Review DE Metabolomics; Type 2 diabetes; Insulin resistance; Insulin secretion ID STIMULATED INSULIN-SECRETION; AMINO-ACID-CONCENTRATIONS; BETA-CELL DYSFUNCTION; FOR-GESTATIONAL-AGE; Y GASTRIC BYPASS; CHILDHOOD OBESITY; GUT MICROBIOME; BRANCHED-CHAIN; FATTY-ACID; SKELETAL-MUSCLE AB Type 2 diabetes (T2D) is increasing worldwide, making identification of biomarkers for detection, staging, and effective prevention strategies an especially critical scientific and medical goal. Fortunately, advances in metabolomics techniques, together with improvements in bioinformatics and mathematical modeling approaches, have provided the scientific community with new tools to describe the T2D metabolome. The metabolomics signatures associated with T2D and obesity include increased levels of lactate, glycolytic intermediates, branched-chain and aromatic amino acids, and longchain fatty acids. Conversely, tricarboxylic acid cycle intermediates, betaine, and other metabolites decrease. Future studies will be required to fully integrate these and other findings into our understanding of diabetes pathophysiology and to identify biomarkers of disease risk, stage, and responsiveness to specific treatments. C1 [Gonzalez-Franquesa, Alba; Burkart, Alison M.; Isganaitis, Elvira; Patti, Mary-Elizabeth] Div Res, 1 Joslin Pl, Boston, MA 02215 USA. RP Patti, ME (reprint author), Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM mary.elizabeth.patti@joslin.harvard.edu OI Gonzalez-Franquesa, Alba/0000-0001-9081-753X FU American Diabetes Association; NIH [T32 DK 007260]; Harold Whitworth Pierce Charitable Trust Postdoctoral Fellowship; Boston Nutrition and Obesity Research Center; NIH; Bristol-Myers Squibb; Janssen; Nuclea; Medimmune; Joslin DRC grant [P30 DK036836]; [K99R00 HD064793] FX AG-F gratefully acknowledges support from the American Diabetes Association (mentored research fellowship to MEP). AMB acknowledges research support from the NIH (T32 DK 007260) and the Harold Whitworth Pierce Charitable Trust Postdoctoral Fellowship. EI acknowledges grant support from K99R00 HD064793 and Boston Nutrition and Obesity Research Center. MEP acknowledges research support from the NIH, American Diabetes Association, Bristol-Myers Squibb, Janssen, Nuclea, Medimmune, and Joslin DRC grant P30 DK036836. NR 135 TC 1 Z9 1 U1 25 U2 27 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 EI 1539-0829 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD AUG PY 2016 VL 16 IS 8 AR 74 DI 10.1007/s11892-016-0763-1 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DU1UR UT WOS:000381995900008 PM 27319324 ER PT J AU Kahraman, S Okawa, ER Kulkarni, RN AF Kahraman, Sevim Okawa, Erin R. Kulkarni, Rohit N. TI Is Transforming Stem Cells to Pancreatic Beta Cells Still the Holy Grail for Type 2 Diabetes? SO CURRENT DIABETES REPORTS LA English DT Review DE Diabetes; Human pluripotent stem cells; Induced pluripotent stem cells; Differentiation; Pancreatic beta cells ID INSULIN-SECRETING CELLS; 10-YEAR FOLLOW-UP; IN-VITRO; PROGENITOR CELLS; GLUCOSE CONTROL; GENETIC ARCHITECTURE; TOLERANCE INDUCTION; SUSCEPTIBILITY LOCI; ANTIDIABETIC DRUGS; WIDE ASSOCIATION AB Diabetes is a progressive disease affecting millions of people worldwide. There are several medications and treatment options to improve the life quality of people with diabetes. One of the strategies for the treatment of diabetes could be the use of human pluripotent stem cells or induced pluripotent stem cells. The recent advances in differentiation of stem cells into insulin-secreting beta-like cells in vitro make the transplantation of the stem cell-derived beta-like cells an attractive approach for treatment of type 1 and type 2 diabetes. While stem cell-derived beta-like cells provide an unlimited cell source for beta cell replacement therapies, these cells can also be used as a platform for drug screening or modeling diseases. C1 [Kahraman, Sevim; Okawa, Erin R.; Kulkarni, Rohit N.] Joslin Diabet Ctr, Sect Islet Cell Biol & Regenerat Med, Boston, MA 02215 USA. [Kahraman, Sevim; Okawa, Erin R.; Kulkarni, Rohit N.] Harvard Med Sch, Boston, MA 02215 USA. [Okawa, Erin R.] Boston Childrens Hosp, Div Endocrinol, Dept Med, Boston, MA 02215 USA. [Kulkarni, Rohit N.] Harvard Stem Cell Inst, Boston, MA 02215 USA. RP Kulkarni, RN (reprint author), Joslin Diabet Ctr, Sect Islet Cell Biol & Regenerat Med, Boston, MA 02215 USA.; Kulkarni, RN (reprint author), Harvard Med Sch, Boston, MA 02215 USA.; Kulkarni, RN (reprint author), Harvard Stem Cell Inst, Boston, MA 02215 USA. EM Rohit.Kulkarni@joslin.harvard.edu NR 67 TC 0 Z9 0 U1 6 U2 7 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 EI 1539-0829 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD AUG PY 2016 VL 16 IS 8 AR 70 DI 10.1007/s11892-016-0764-0 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DU1UR UT WOS:000381995900004 PM 27313072 ER PT J AU Schumacher, TN Hacohen, N AF Schumacher, Ton N. Hacohen, Nir TI Editorial overview: Cancer immunology: genomics & biomarkers: Cancer immunity through the prism of genomics and proteomics SO CURRENT OPINION IN IMMUNOLOGY LA English DT Editorial Material C1 [Schumacher, Ton N.] Netherlands Canc Inst, Div Immunol, Amsterdam, Netherlands. [Hacohen, Nir] Broad Inst Harvard & MIT, 149 13th St, Charlestown, MA 02129 USA. [Hacohen, Nir] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02115 USA. RP Schumacher, TN (reprint author), Netherlands Canc Inst, Div Immunol, Amsterdam, Netherlands. EM t.schumacher@nki.nl; nhacohen@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 4 U2 4 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 EI 1879-0372 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD AUG PY 2016 VL 41 BP IX EP X DI 10.1016/j.coi.2016.07.006 PG 2 WC Immunology SC Immunology GA DU7TI UT WOS:000382417100002 PM 27506117 ER PT J AU Miao, D Van Allen, EM AF Miao, Diana Van Allen, Eliezer M. TI Genomic determinants of cancer immunotherapy SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID CELL LUNG-CANCER; CTLA-4 BLOCKADE; METASTATIC MELANOMA; UNTREATED MELANOMA; PATIENT SURVIVAL; PD-1 BLOCKADE; SIPULEUCEL-T; PHASE-II; IPILIMUMAB; NIVOLUMAB AB Cancer immunotherapies including therapeutic vaccines, adoptive cell transfer, oncolytic viruses, and immune checkpoint blockade yield durable responses in many cancer types, but understanding of predictors of response is incomplete. Genomic characterization of human cancers has already contributed to the success of targeted therapies; in cancer immunotherapy, identification of tumor-specific antigens through whole-exome sequencing may be key to designing individualized, highly immunogenic therapeutic vaccines. Additionally, pre-treatment tumor mutational and gene expression signatures can predict which patients are most likely to benefit from cancer immunotherapy. Continued work in harnessing genomic, transcriptomic, and immunological data from clinical cohorts of immunotherapy-treated patients will bring the promises of precision medicine to immuno-oncology. C1 [Miao, Diana; Van Allen, Eliezer M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Miao, Diana; Van Allen, Eliezer M.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Van Allen, Eliezer M.] Dana Farber Canc Inst, Ctr Canc Precis Med, Boston, MA 02215 USA. RP Van Allen, EM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.; Van Allen, EM (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.; Van Allen, EM (reprint author), Dana Farber Canc Inst, Ctr Canc Precis Med, Boston, MA 02215 USA. EM eliezerm_vanallen@dfci.harvard.edu NR 46 TC 3 Z9 3 U1 6 U2 6 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 EI 1879-0372 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD AUG PY 2016 VL 41 BP 32 EP 38 DI 10.1016/j.coi.2016.05.010 PG 7 WC Immunology SC Immunology GA DU7TI UT WOS:000382417100007 PM 27254251 ER PT J AU Wucherpfennig, KW Cartwright, ANR AF Wucherpfennig, Kai W. Cartwright, Adam N. R. TI Genetic screens to study the immune system in cancer SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID WIDE CRISPR SCREEN; FUNCTIONAL GENOMICS; TUMOR SUPPRESSORS; SHRNA LIBRARIES; HUMAN-CELLS; MOUSE; DIFFERENTIATION; REGULATORS; DISCOVERY; LYMPHOMA AB RNA interference and CRISPR/Cas9 technologies now enable systematic discovery of genes that regulate key pathways in the complex interaction between immune cells and tumor cells. Discovery screens are feasible in an in vivo setting, allowing identification of genes that limit the effectiveness of anti-tumor immunity. In vivo discovery screens can be informed by single cell RNA-seq experiments that define the differentially expressed genes between functionally distinct immune cell subpopulations, both in humans and relevant animal models. Novel targets for cancer immunotherapy are being defined by the in depth functional annotation of immunosuppressive pathways in the tumor microenvironment. C1 [Wucherpfennig, Kai W.; Cartwright, Adam N. R.] Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA. [Wucherpfennig, Kai W.; Cartwright, Adam N. R.] Harvard Med Sch, Dept Neurol, Boston, MA 02115 USA. [Wucherpfennig, Kai W.] Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA.; Wucherpfennig, KW (reprint author), Harvard Med Sch, Dept Neurol, Boston, MA 02115 USA.; Wucherpfennig, KW (reprint author), Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. EM kai_wucherpfennig@dfci.harvard.edu FU Melanoma Research Alliance; Bridge Project of MIT/Koch Institute; Dana-Farber/Harvard Cancer Center; NIH [1R01CA173750] FX This work was supported by grants from the Melanoma Research Alliance, the Bridge Project of MIT/Koch Institute and Dana-Farber/Harvard Cancer Center, and the NIH (1R01CA173750). NR 28 TC 0 Z9 0 U1 10 U2 10 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 EI 1879-0372 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD AUG PY 2016 VL 41 BP 55 EP 61 DI 10.1016/j.coi.2016.05:007 PG 7 WC Immunology SC Immunology GA DU7TI UT WOS:000382417100010 PM 27309352 ER PT J AU Schumacher, TN Hacohen, N AF Schumacher, Ton N. Hacohen, Nir TI Neoantigens encoded in the cancer genome SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID T-CELLS; METASTATIC MELANOMA; CHECKPOINT BLOCKADE; CTLA-4 BLOCKADE; PD-1 BLOCKADE; NEO-ANTIGENS; TUMOR; IMMUNOTHERAPY; LYMPHOCYTES; THERAPY AB Somatic mutations in the genome represent one of the major drivers of malignancy. However, non-synonymous mutations are also a source of mutated peptides that are presented by HLA molecules to induce protective CD4 and CD8 T cell responses. Consistent with this notion, the mutation burden of a tumor is correlated with local immunity as well as outcome of therapy and patient survival. Furthermore, neoantigen-specific T cells appear sufficient to control tumors prophylactically and therapeutically. While the role of neoantigens as a determinant of the foreignness of human cancers is now well established, major questions, including the relative importance of clonal vs subclonal neoantigens, and CD4 vs CD8 T cells, remain unanswered. We expect continued animal studies to address some of the open issues and ongoing clinical trials to establish the utility of therapeutic strategies to enhance neoantigen-specific T cell responses in human cancer. C1 [Schumacher, Ton N.] Netherlands Canc Inst, Div Immunol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands. [Hacohen, Nir] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Hacohen, Nir] Massachusetts Gen Hosp, Ctr Canc Immunol, Boston, MA 02114 USA. [Hacohen, Nir] Broad Inst Harvard & MIT, Cambridge, MA USA. RP Schumacher, TN (reprint author), Netherlands Canc Inst, Div Immunol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.; Hacohen, N (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.; Hacohen, N (reprint author), Massachusetts Gen Hosp, Ctr Canc Immunol, Boston, MA 02114 USA.; Hacohen, N (reprint author), Broad Inst Harvard & MIT, Cambridge, MA USA. EM t.schumacher@nki.nl; nhacohen@mgh.harvard.edu FU Dutch Cancer Society Queen Wilhelmina Award [NKI 2013-6122]; Blavatnik Family Foundation; Dutch Cancer Society [NKI 2012-5463] FX This work was supported by the Dutch Cancer Society Queen Wilhelmina Award NKI 2013-6122 and Dutch Cancer Society grant NKI 2012-5463 (to TNS), and the Blavatnik Family Foundation (to NH). We would like to thank E. Fritsch (Neon Therapeutics) for valuable discussions. TNS and NH are founders and stockholders of Neon Therapeutics. TNS is employee and stockholder of Kite Pharma. NR 44 TC 0 Z9 0 U1 14 U2 20 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 EI 1879-0372 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD AUG PY 2016 VL 41 BP 98 EP 103 DI 10.1016/j.coi.2016.07.005 PG 6 WC Immunology SC Immunology GA DU7TI UT WOS:000382417100016 PM 27518850 ER PT J AU Cahn, A Raz, I Mosenzon, O Leibowitz, G Yanuv, I Rozenberg, A Iqbal, N Hirshberg, B Sjostrand, M Stahre, C Im, K Kanevsky, E Scirica, BM Bhatt, DL Braunwald, E AF Cahn, Avivit Raz, Itamar Mosenzon, Ofri Leibowitz, Gil Yanuv, Ilan Rozenberg, Aliza Iqbal, Nayyar Hirshberg, Boaz Sjostrand, Mikaela Stahre, Christina Im, KyungAh Kanevsky, Estella Scirica, Benjamin M. Bhatt, Deepak L. Braunwald, Eugene TI Predisposing Factors for Any and Major Hypoglycemia With Saxagliptin Versus Placebo and Overall: Analysis From the SAVOR-TIMI 53 Trial SO DIABETES CARE LA English DT Article ID BASE-LINE CHARACTERISTICS; BLOOD-GLUCOSE CONTROL; DIABETES-MELLITUS; VASCULAR OUTCOMES; TYPE-2; RISK; METAANALYSIS; INSULIN; COMPLICATIONS; HYPERGLYCEMIA AB OBJECTIVETo analyze the impact of adding saxagliptin versus placebo on the risk for hypoglycemia and to identify predictors of any and major hypoglycemia in patients with type 2 diabetes included in the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) study.RESEARCH DESIGN AND METHODSPatients with type 2 diabetes (n = 16,492) were randomized to saxagliptin or placebo and followed for a median of 2.1 years. Associations between any hypoglycemia (symptomatic or glucose measurement <54 mg/dL) or major hypoglycemia (requiring extended assistance) and patient characteristics overall and by treatment allocation were studied.RESULTSAt least one hypoglycemic event was reported in 16.6% of patients, and 1.9% reported at least one major event. Patients allocated to saxagliptin versus placebo experienced higher rates of any (hazard ratio [HR] 1.16 [95% CI 1.08, 1.25]; P < 0.001) or major (HR 1.26 [1.01, 1.58]; P = 0.038) hypoglycemia. Hypoglycemia rates (any or major) were increased with saxagliptin in patients taking sulfonylureas (SURs) but not in those taking insulin. Rates were increased with saxagliptin in those with baseline HbA(1c) 7.0% and not in those with baseline HbA(1c) >7.0%. Multivariate analysis of the overall population revealed that independent predictors of any hypoglycemia were as follows: allocation to saxagliptin, long duration of diabetes, increased updated HbA(1c), macroalbuminuria, moderate renal failure, SUR use, and insulin use. Predictors of major hypoglycemia were allocation to saxagliptin, advanced age, black race, reduced BMI, long duration of diabetes, declining renal function, microalbuminuria, and use of short-acting insulin. Among SURs, glibenclamide was associated with increased risk of major but not any hypoglycemia.CONCLUSIONSThe identification of patients at risk for hypoglycemia can guide physicians to better tailor antidiabetic therapy. C1 [Cahn, Avivit; Raz, Itamar; Mosenzon, Ofri; Leibowitz, Gil; Yanuv, Ilan; Rozenberg, Aliza] Hadassah Hebrew Univ Hosp, Diabet Unit, Jerusalem, Israel. [Cahn, Avivit; Leibowitz, Gil] Hadassah Hebrew Univ Hosp, Endocrinol & Metab Unit, Jerusalem, Israel. [Iqbal, Nayyar] AstraZeneca Res & Dev, Gaithersburg, MD USA. [Hirshberg, Boaz] MedImmune, Gaithersburg, MD USA. [Sjostrand, Mikaela; Stahre, Christina] AstraZeneca, Gothenburg, Sweden. [Im, KyungAh; Kanevsky, Estella; Scirica, Benjamin M.; Bhatt, Deepak L.; Braunwald, Eugene] Harvard Med Sch, Brigham & Womens Hosp, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA USA. RP Raz, I (reprint author), Hadassah Hebrew Univ Hosp, Diabet Unit, Jerusalem, Israel. EM ntv502@netvision.net.il FU AstraZeneca; Bristol-Myers Squibb; Boehringer Ingelheim; Elli Lilly and Company; Merck Sharp Dohme; Novartis; Novo Nordisk; Sanofi; Hadassah Hebrew University Hospital-Novo Nordisk; TIMI Study; Daiichi Sankyo; GlaxoSmithKline; Gilead; Eisai; Biogen Idec; Boehringer; Ingelheim; Boston Clinical Research Institute; Covance; Dr. Reddy's Laboratory; Elsevier Practice Update Cardiology; Forest Laboratory; GE Healthcare; Lexicon; St. Jude Medical; University of Calgary; TIMI Study Group; Brigham; Women's Hospital FX The SAVOR-TIMI 53 trial was funded by AstraZeneca and Bristol-Myers Squibb. A.C. reports receipt of consulting fees and payment for lectures from AstraZeneca, Boehringer Ingelheim, Elli Lilly and Company, Merck Sharp & Dohme, Novartis, Novo Nordisk, and Sanofi. I.R. has served on the advisory board for AstraZeneca/Bristol-Meyers Squibb, Eli Lilly and Company, Medscape LLC, Merck Sharp & Dohme, Novo Nordisk, Sanofi, Orgenesis, SmartZyme Innovation Ltd., and LabStyle Innovations Corp.; has been a consultant for AstraZeneca/Bristol-Meyers Squibb, Insuline Medical, Gili Medical, KAMADA, and FutuRx; has served on the speaker's bureau for AstraZeneca/Bristol-Meyers Squibb, Eli Lilly and Company, Johnson & Johnson, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi, and Teva; and is a stock-/shareholder of Insuline Medical, LabStyle Innovations Corp., SmartZyme Innovation Ltd., Orgenesis, and GlucoMe. O.M. has served on the advisory board for Novo Nordisk, Eli Lilly and Company, Sanofi, Merck Sharp & Dohme, Boehringer Ingelheim, Janssen, Novartis, and AstraZeneca; had grants paid to their institution as a study physician by AstraZeneca and Bristol-Myers Squibb; has received research grant support through Hadassah Hebrew University Hospital-Novo Nordisk; and has served on the speaker's bureau for AstraZeneca, Bristol-Myers Squibb, Novo Nordisk, Eli Lilly and Company, Sanofi, Novartis, Merck Sharp & Dohme, and Boehringer Ingelheim. G.L. has received speaker's honoraria from Novartis, Novo Nordisk, Eli Lilly and Company, and Sanofi and has attended advisory board meetings for Sanofi and AstraZeneca. N.I., M.S., and C.S. are employees of AstraZeneca. B.H. is an employee of MedImmune, a subsidiary of AstraZeneca. B.M.S. has received research grants via the TIMI Study and Brigham and Women's Hospital from AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Gilead, Eisai, and Merck Sharp & Dohme and consulting fees from AstraZeneca, Biogen Idec, Boehringer Ingelheim, Boston Clinical Research Institute, Bristol-Myers Squibb, Covance, Dr. Reddy's Laboratory, Eisai, Elsevier Practice Update Cardiology, Forest Laboratory, GE Healthcare, Gilead, GlaxoSmithKline, Lexicon, Merck Sharp & Dohme, St. Jude Medical, and the University of Calgary. D.L.B. has served on the advisory board for Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; has served on the board of directors for Boston VA Research Institute and Society of Cardiovascular Patient Care; has been the chair of the American Heart Association Quality Oversight Committee; has served on the data monitoring committee for the Duke Clinical Research Institute, the Harvard Clinical Research Institute, the Mayo Clinic, and the Population Health Research Institute; has received honoraria from the American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.; org), Belvoir Publications (Editor in Chief, Harvard Heart Letter), the Duke Clinical Research Institute (clinical trial steering committees), the Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (editor in chief, Journal of Invasive Cardiology), the Journal of the American College of Cardiology (guest editor and associate editor), the Population Health Research Institute (clinical trial steering committee), Slack Publications (chief medical editor, Cardiology Today's Intervention), the Society of Cardiovascular Patient Care (secretary/treasurer), WebMD (continuing medical education steering committees), Clinical Cardiology (deputy editor), NCDR-ACTION Registry Steering Committee (vice chair), and VA CART Research and Publications Committee (chair); has received research funding from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Forest Laboratories, Ischemix, Medtronic, Pfizer, Roche, Sanofi, and The Medicines Company; has received royalties from Elsevier (editor, Cardiovascular Intervention: A Companion to Braunwald's Heart Disease); has served as site co-investigator for Biotronik, Boston Scientific, and St. Jude Medical; is a trustee of the American College of Cardiology; and has performed unfunded research for FlowCo, PLx Pharma, and Takeda. E.B. has received research grants via the TIMI Study Group and Brigham and Women's Hospital from Merck Sharp & Dohme, Daiichi Sankyo, GlaxoSmithKline, Bristol-Myers Squibb, Duke University, AstraZeneca, Johnson & Johnson, Sanofi, and Novartis; has received consulting fees from The Medicines Company, Sanofi, and Theravance Biopharma; and has received payment for lectures from Menarini Group, Bayer, and Medscape. No other potential conflicts of interest relevant to this article were reported. NR 35 TC 2 Z9 2 U1 2 U2 2 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 AUG PY 2016 VL 39 IS 8 BP 1329 EP 1337 DI 10.2337/dc15-2763 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DT4CN UT WOS:000381427800025 PM 27222508 ER PT J AU Lachin, JM Bebu, I Nathan, DM Zinman, B Brillon, D Backlund, JYC Cleary, P Orchard, TJ AF Lachin, John M. Bebu, Ionut Nathan, David M. Zinman, Bernard Brillon, David Backlund, Jye-Yu C. Cleary, Patricia Orchard, Trevor J. CA Diabet Control Complications Trial TI Mortality in Type 1 Diabetes in the DCCT/EDIC Versus the General Population SO DIABETES CARE LA English DT Article ID ALL-CAUSE MORTALITY; LONG-TERM MORTALITY; FOLLOW-UP; PITTSBURGH EPIDEMIOLOGY; COMPLICATIONS TRIAL; INTENSIVE TREATMENT; NATIONWIDE COHORTS; MELLITUS; INTERVENTIONS; ASSOCIATION AB OBJECTIVEHistorically, mortality in type 1 diabetes has exceeded that in the general population. We compared mortality in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study cohort to that of the current general U.S. population.RESEARCH DESIGN AND METHODSThe DCCT (1983-1993) compared intensive versus conventional therapy, with HbA(1c) levels of approximate to 7 vs. 9%, respectively, over an average of 6.5 years of treatment. EDIC is the observational follow-up study of the DCCT (1994 to the present). Vital status was ascertained for 97.5% of the original DCCT cohort (n = 1,441) after a mean of 27 years follow-up. Expected mortality during DCCT/EDIC was estimated using the current age-, sex-, and race-specific risks in the general U.S. population, and the observed versus expected mortality compared using standardized mortality ratios (SMRs) and Poisson regression models.RESULTSMortality in the DCCT intensive therapy group was nonsignificantly lower than that in the general U.S. population (SMR = 0.88 [95% CI 0.67, 1.16]), whereas mortality in the DCCT conventional therapy group was significantly greater than that in the general population (SMR = 1.31 [95% CI 1.05, 1.65]). The SMR increased with increasing mean HbA(1c), and above an HbA(1c) of 9%, the rate of increase in SMR among females was greater than that among males.CONCLUSIONSOverall mortality in the combined DCCT/EDIC cohort was similar to that of the general population but was higher in the DCCT conventional therapy group. Mortality increased significantly with increasing mean HbA(1c), more so among females than males, especially for HbA(1c) >9%. C1 [Lachin, John M.; Bebu, Ionut; Backlund, Jye-Yu C.; Cleary, Patricia] George Washington Univ, Biostat Ctr, Rockville, MD 20052 USA. [Nathan, David M.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Zinman, Bernard] Univ Toronto, Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada. [Brillon, David] Weill Cornell Med Coll, New York, NY USA. [Orchard, Trevor J.] Univ Pittsburgh, Pittsburgh, PA USA. RP Lachin, JM (reprint author), George Washington Univ, Biostat Ctr, Rockville, MD 20052 USA. EM jml@bsc.gwu.edu OI Lachin, John/0000-0001-9838-2841 FU Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases [U01 DK094176, U01 DK094157]; National Eye Institute; National Institute of Neurological Disorders and Stroke; General Clinical Research Centers Program; Clinical and Translational Science Center Program, Bethesda, MD FX The DCCT/EDIC has been supported by cooperative agreement grants (1982-1993 and 2012-2017) and contracts (1982-2012) with the Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases (current grant numbers U01 DK094176 and U01 DK094157) and by the National Eye Institute, the National Institute of Neurological Disorders and Stroke, the General Clinical Research Centers Program (1993-2007), and the Clinical and Translational Science Center Program (2006 to present), Bethesda, MD. NR 31 TC 0 Z9 0 U1 3 U2 3 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 AUG PY 2016 VL 39 IS 8 BP 1378 EP 1383 DI 10.2337/dc15-2399 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DT4CN UT WOS:000381427800031 ER PT J AU Mifflin, J AF Mifflin, Jeffrey TI When I Was a Photographer SO EARLY POPULAR VISUAL CULTURE LA English DT Book Review C1 [Mifflin, Jeffrey] Massachusetts Gen Hosp, Arch & Special Collect, Boston, MA 02114 USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp, Arch & Special Collect, Boston, MA 02114 USA. EM JMIFFLIN@mgh.harvard.edu NR 1 TC 0 Z9 0 U1 2 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1746-0654 EI 1746-0662 J9 EARLY POPUL VIS CULT JI Early Popul. Vis. Cult. PD AUG PY 2016 VL 14 IS 3 BP 289 EP 291 DI 10.1080/17460654.2016.1189382 PG 3 WC Humanities, Multidisciplinary SC Arts & Humanities - Other Topics GA DU8WK UT WOS:000382496200007 ER PT J AU Yang, L Kirby, JE Sunwoo, H Lee, JT AF Yang, Lin Kirby, James E. Sunwoo, Hongjae Lee, Jeannie T. TI Female mice lacking Xist RNA show partial dosage compensation and survive to term SO GENES & DEVELOPMENT LA English DT Article DE genome balance; inverse effect; X inactivation; Xist; dosage compensation; knockout mouse; transcriptomics ID X-CHROMOSOME INACTIVATION; EARLY MOUSE EMBRYOS; GENE-EXPRESSION; PREFERENTIAL INACTIVATION; DROSOPHILA-MELANOGASTER; CARDIOMYOCYTE NUMBER; UP-REGULATION; LINKED GENES; MAMMALS; MAINTENANCE AB X-chromosome inactivation (XCI) compensates for differences in X-chromosome number between male and female mammals. XCI is orchestrated by Xist RNA, whose expression in early development leads to transcriptional silencing of one X chromosome in the female. Knockout studies have established a requirement for Xist with inviability of female embryos that inherit an Xist deletion from the father. Here, we report that female mice lacking Xist RNA can, surprisingly, develop and survive to term. Xist-null females are born at lower frequency and are smaller at birth, but organogenesis is mostly normal. Transcriptomic analysis indicates significant overexpression of hundreds of X-linked genes across multiple tissues. Therefore, Xist-null mice can develop to term in spite of a deficiency of dosage compensation. However, the degree of X-autosomal dosage imbalance was less than anticipated (1.14-fold to 1.36-fold). Thus, partial dosage compensation can be achieved without Xist, supporting the idea of inherent genome balance. Nevertheless, to date, none of the mutant mice has survived beyond weaning stage. Sudden death is associated with failure of postnatal organ maturation. Our data suggest Xist-independent mechanisms of dosage compensation and demonstrate that small deviations from X-autosomal balance can have profound effects on overall fitness. C1 [Yang, Lin; Sunwoo, Hongjae; Lee, Jeannie T.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. [Yang, Lin; Sunwoo, Hongjae; Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Yang, Lin; Sunwoo, Hongjae; Lee, Jeannie T.] Harvard Med Sch, Dept Genet, Boston, MA 02114 USA. [Kirby, James E.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02114 USA. RP Lee, JT (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA.; Lee, JT (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.; Lee, JT (reprint author), Harvard Med Sch, Dept Genet, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu FU Agency for Science, Technology, and Research of Singapore; National Institutes of Health [DA-R01-36895]; Rett Syndrome Research Trust FX We thank R. Jaenisch for Xistfl/fl mice; R. Mostoslaysky, K. Hochedlinger, W. Bender, B. Payer, and the Lee laboratory for valuable advice and feedback; D. Lessing, T. Dial, and B. del Rosario for critical reading of the manuscript, and W. Press for mouse colony maintenance. This work was supported by grant funding from the Agency for Science, Technology, and Research of Singapore (to L.Y.), the National Institutes of Health (DA-R01-36895 to J.T.L.), and the Rett Syndrome Research Trust (to J.T.L.). J.T.L. is also an Investigator of the Howard Hughes Medical Institute. NR 62 TC 2 Z9 2 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 EI 1549-5477 J9 GENE DEV JI Genes Dev. PD AUG 1 PY 2016 VL 30 IS 15 BP 1747 EP 1760 DI 10.1101/gad.281162.116 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA DU7RR UT WOS:000382412800006 PM 27542829 ER PT J AU Grussendorf, KA Trezza, CJ Salem, AT Al-Hashimi, H Mattingly, BC Kampmeyer, DE Khan, LA Hall, DH Gobel, V Ackley, BD Buechner, M AF Grussendorf, Kelly A. Trezza, Christopher J. Salem, Alexander T. Al-Hashimi, Hikmat Mattingly, Brendan C. Kampmeyer, Drew E. Khan, Liakot A. Hall, David H. Goebel, Verena Ackley, Brian D. Buechner, Matthew TI Facilitation of Endosomal Recycling by an IRG Protein Homolog Maintains Apical Tubule Structure in Caenorhabditis elegans SO GENETICS LA English DT Article DE tubulogenesis; trafficking; endosomes; IRG; immunity-related GTPase ID RICH INTESTINAL PROTEIN; NUCLEOTIDE EXCHANGE FACTOR; EXCRETORY CELL; C-ELEGANS; PORPHOBILINOGEN DEAMINASE; FACIOGENITAL DYSPLASIA; RESISTANCE GTPASES; TOXOPLASMA-GONDII; INDUCIBLE GTPASES; IMMUNE-RESPONSE AB Determination of luminal diameter is critical to the function of small single-celled tubes. A series of EXC proteins, including EXC-1, prevent swelling of the tubular excretory canals in Caenorhabditis elegans. In this study, cloning of exc-1 reveals it to encode a homolog of mammalian IRG proteins, which play roles in immune response and autophagy and are associated with Crohn's disease. Mutants in exc-1 accumulate early endosomes, lack recycling endosomes, and exhibit abnormal apical cytoskeletal structure in regions of enlarged tubules. EXC-1 interacts genetically with two other EXC proteins that also affect endosomal trafficking. In yeast two-hybrid assays, wild-type and putative constitutively active EXC-1 binds to the LIM-domain protein EXC-9, whose homolog, cysteine-rich intestinal protein, is enriched in mammalian intestine. These results suggest a model for IRG function in forming and maintaining apical tubule structure via regulation of endosomal recycling. C1 [Grussendorf, Kelly A.; Trezza, Christopher J.; Salem, Alexander T.; Al-Hashimi, Hikmat; Mattingly, Brendan C.; Ackley, Brian D.; Buechner, Matthew] Univ Kansas, Dept Mol Biosci, 1200 Sunnyside Dr,8035 Haworth Hall, Lawrence, KS 66045 USA. [Grussendorf, Kelly A.; Kampmeyer, Drew E.] Minnesota State Univ, Dept Biol Sci, Mankato, MN 56001 USA. [Khan, Liakot A.; Goebel, Verena] Harvard Med Sch, Massachusetts Gen Hosp, Mucosal Immunol & Biol Res Ctr, Dev Biol & Genet Core, Boston, MA 02114 USA. [Hall, David H.] Albert Einstein Coll Med, Dept Neurosci, Ctr Caenorhabditis Elegans Anat, Bronx, NY 10461 USA. [Grussendorf, Kelly A.] Univ Dubuque, Dept Nat & Appl Sci, Goldthorp Sci Ctr 309A, 1150 N Algona St, Dubuque, IA 52001 USA. [Mattingly, Brendan C.] Univ Kansas, Regents Ctr, 12600 Quivira Rd, Overland Pk, KS 66213 USA. RP Buechner, M (reprint author), Univ Kansas, Dept Mol Biosci, 1200 Sunnyside Dr,8035 Haworth Hall, Lawrence, KS 66045 USA. EM buechner@ku.edu FU National Institute of General Medical Sciences [P41-GM-103311]; NIH Office of Research Infrastructure Programs [P40-OD-010440]; National Institutes of Health (NIH) [R03-NS-067323]; National Science Foundation; University of Kansas Graduate Research Fund [2301744]; NIH Initiative for Maximizing Student Development Program [R25-GM-62232]; NIH [OD-010943] FX We gratefully acknowledge helpful discussions with Stuart Macdonald, Barth Grant, Erik Lundquist, Yoshiaki Azuma, Jamie Alan-Olson, Meera Sundaram, Kathy Suprenant, Robert S. Cohen, and the elusive Edward M. Hedgecock. We thank Shai Shaham for the gift of the worm strain containing amphid sheath cell marker construct nsIs53. Plasmid L3691 was a gift from A. Fire. We thank Nancy R. Hall for help with statistical analyses. Molecular graphics and analyses were performed with the University of California, San Francisco (UCSF)'s Chimera package, developed by the UCSF Resource for Biocomputing, Visualization, and Informatics (supported by National Institute of General Medical Sciences grant P41-GM-103311). Some strains were provided by the Caenorhabditis Genetics Center, which is funded by the NIH Office of Research Infrastructure Programs (grant P40-OD-010440). Parts of this work were supported by National Institutes of Health (NIH; grant R03-NS-067323). M.B. was supported by the National Science Foundation. K.A.G. was supported by the University of Kansas Graduate Research Fund award no. 2301744. C.T. was supported by the NIH Initiative for Maximizing Student Development Program grant R25-GM-62232. D.H.H. was supported by NIH grant OD-010943. NR 75 TC 0 Z9 0 U1 3 U2 3 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD AUG PY 2016 VL 203 IS 4 BP 1789 EP + DI 10.1534/genetics.116.192559 PG 23 WC Genetics & Heredity SC Genetics & Heredity GA DV0PZ UT WOS:000382622700023 PM 27334269 ER PT J AU Rauh-Hain, JA Birrer, M del Carmen, MG AF Rauh-Hain, J. Alejandro Birrer, Michael del Carmen, Marcela G. TI Carcinosarcoma of the ovary, fallopian tube, and peritoneum: Prognostic factors and treatment modalities SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Ovarian cancer; Ovarian carcinosarcoma; Chemotherapy ID MIXED MESODERMAL TUMORS; PLATINUM-BASED CHEMOTHERAPY; GYNECOLOGIC-ONCOLOGY-GROUP; RECURRENT EPITHELIAL OVARIAN; MULLERIAN TUMORS; COMBINATION CHEMOTHERAPY; SURGICAL CYTOREDUCTION; UTERINE CARCINOSARCOMA; PHASE-II; CANCER AB Objective. Ovarian carcinosarcoma (OCS) is a rare malignancy accounting for only 1-4% of all ovarian cancers. The treatment of OCS is largely based on data from small case series and management of other histologic subtypes of epithelial ovarian cancer. We reviewed the literature pertinent to the pathology, pathogenesis, diagnosis, and management of women with OCS. Methods. MEDLINE was searched in English for literature on OCS, focusing on the past 30 years. Given the rarity of this tumor, studies were not limited by design or number of reported patients. Results. Molecular, epidemiologic, genetic, and histologic data indicate that most OCS are monoclonal. Patients with OCS generally present with advanced stage disease. Most of the available retrospective studies support the role of cytoreductive surgery in the management of OCS, with optimal debulking associated with improved survival. Platinum-based chemotherapy is the current accepted adjuvant treatment. Given the limited data regarding the management of recurrent OCS, patients are usually treated similarly to women diagnosed with other subtypes of epithelial ovarian cancer. Conclusion. OCS represent a rare and aggressive histologic subtype of epithelial ovarian cancer. The goal of surgery is comprehensive staging in patients with early-stage disease and optimal cytoreduction patients with advanced-stage tumors. Platinum-based chemotherapy is the mainstay of adjuvant systemic treatment. Future studies are needed in order to elucidate the molecular basis for OCS and to evaluate the role of targeted therapy in its management. (C) 2016 Elsevier Inc. All rights reserved. C1 [Rauh-Hain, J. Alejandro; del Carmen, Marcela G.] Harvard Med Sch, Massachusetts Gen Hosp, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA USA. [Birrer, Michael] Harvard Med Sch, Massachusetts Gen Hosp, Div Med Oncol, Boston, MA USA. RP Rauh-Hain, JA (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol Vincent Obstet & Gynecol, 55 Fruit St,Yawkey 9 E, Boston, MA 02114 USA. EM jrauh-hain@partners.org FU National Cancer Institute at the National Institutes of Health [R25CA092203]; Deborah Kelly Center for Outcomes Research, Massachusetts General Hospital FX This work was supported by R25CA092203 from the National Cancer Institute at the National Institutes of Health and The Deborah Kelly Center for Outcomes Research, Massachusetts General Hospital. NR 62 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD AUG PY 2016 VL 142 IS 2 BP 248 EP 254 DI 10.1016/j.ygyno.2016.06.003 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA DS4EH UT WOS:000380733700008 PM 27321238 ER PT J AU Esselen, KM Terry, KL Samuel, A Elias, KM Davis, M Welch, WR Muto, MG Ng, SW Berkowitz, RS AF Esselen, Katharine M. Terry, Kathryn L. Samuel, Anicka Elias, Kevin M. Davis, Michelle Welch, William R. Muto, Michael G. Ng, Shu-Wing Berkowitz, Ross S. TI Endosalpingiosis: More than just an incidental finding at the time of gynecologic surgery? SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Endosalpingiosis; Fallopian tube; Endometriosis; Uterine cancer; Ovarian cancer; Serous ovarian neoplasms ID CHRONIC PELVIC PAIN; SEROUS TUMORS; OVARIAN-CANCER; TUBAL ORIGIN; ENDOMETRIOSIS; LAPAROSCOPY; CARCINOMA; PRECURSOR AB Objective. To describe the clinical characteristics of patients with endosalpingiosis (ES) and examine its association with endometriosis and gynecologic malignancies. Methods. We queried the medical record for patients who underwent gynecologic surgery (Gynecologic Surgery Cohort (GSC), n = 58,161) from 1998 to 2013 at a single institution for the presence of "endosalpingiosis" (ES). Demographic and clinical characteristics were collected for patients with pathologically confirmed ES (n = 838). Within GSC, we compared the frequency of endometriosis and gynecologic malignancies with and without ES. We estimated the expected distribution of ovarian cancer subtypes using cases from the New England Case Control Study (NECC). We used chi-square tests to test for significant differences in frequency distributions and unconditional logistic regression to calculate multivariate odds ratios for the association between ES and ovarian cancer subtypes. Results. We observed concurrent endometriosis (p < 0.0001), uterine cancer (p < 0.0001), and ovarian cancer (p < 0.0001) more frequently in women with ES. Women from the GSC with ES and ovarian cancer were more likely to have serous borderline (OR = 10.2, 95% CI = 5.1-20.7), clear cell (OR = 3.0, 95% CI = 1.1-8.0), and invasive mucinous tumors (OR = 5.0, 95% CI = 1.5-16.6) as compared to ovarian cancer cases from the NECC without ES, after accounting for age, race, menopausal status, parity, tubal ligation, and endometriosis. Conclusion. Women with ES are more likely to also be diagnosed with endometriosis, uterine, and ovarian cancers. Further study is needed to understand these associations so we may appropriately counsel patients with ES diagnosed at time of gynecologic surgery. (C) 2016 Elsevier Inc. All rights reserved. C1 [Esselen, Katharine M.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA USA. [Terry, Kathryn L.] Harvard Med Sch, Brigham & Womens Hosp, Dept Obstet & Gynecol, Obstet & Gynecol Epidemiol Ctr, Boston, MA USA. [Samuel, Anicka; Elias, Kevin M.; Davis, Michelle; Muto, Michael G.; Berkowitz, Ross S.] Harvard Med Sch, Dana Farber Canc Inst, Brigham & Womens Hosp, Div Gynecol Oncol,Dept Obstet & Gynecol, Boston, MA USA. [Welch, William R.] Harvard Med Sch, Brigham & Womens Hosp, Div Womens & Perinatal Pathol, Dept Pathol, Boston, MA USA. [Ng, Shu-Wing] Harvard Med Sch, Brigham & Womens Hosp, Dept Obstet & Gynecol, Lab Gynecol Oncol,Div Gynecol Oncol, Boston, MA USA. RP Esselen, KM (reprint author), Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, 330 Brookline Ave, Boston, MA 02215 USA. EM kesselen14@gmail.com FU Expanding the Boundaries, Brigham and Women's Hospital, Internal Research Funding FX This project was funded by Expanding the Boundaries, Brigham and Women's Hospital, Internal Research Funding. NR 22 TC 2 Z9 2 U1 4 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD AUG PY 2016 VL 142 IS 2 BP 255 EP 260 DI 10.1016/j.ygyno.2016.05.036 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA DS4EH UT WOS:000380733700009 PM 27261327 ER PT J AU Uppal, S del Carmen, MG Rice, LW Reynolds, RK Jolly, S Bregar, A Abdelsattar, ZM Rauh-Hain, JA AF Uppal, Shitanshu del Carmen, Marcela G. Rice, Laurel W. Reynolds, R. Kevin Jolly, Shruti Bregar, Amy Abdelsattar, Zaid M. Rauh-Hain, J. Alejandro TI Variation in care in concurrent chemotherapy administration during radiation for locally advanced cervical cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Cervix cancer; Concurrent chemo radiation; Health disparities; Variation in care ID ADJUVANT CHEMOTHERAPY; IMPROVED SURVIVAL; NCCN GUIDELINES; BREAST-CANCER; NIH ROADMAP; OUTCOMES; STAGE; ADHERENCE; IMPACT; VOLUME AB Background. To evaluate the usage of concurrent chemo-radiotherapy (C-CRT) for the treatment of locally advanced cervical cancer. Methods. Patients with locally invasive cervical carcinoma diagnosed between January 1, 2004 and December 31, 2012 from the National Cancer Database (NCDB) were included. Outcomes for patients undergoing radiation therapy only, 'RT alone' group were compared to those receiving chemotherapy concurrent with radiation C-CRT group'. Trends in utilization of C-CRT and factors associated with the deviation from standard of care were explored. Lastly, the effect of hospital volume on utilization of C-CRT was investigated. Results. A total of 18,164 patients undergoing definitive radiation therapy were available for analysis. Utilization of C-CRT increased from 72.4% in 2004 to 84.3% in 2012 (p-trend < 0.001). After adjusting for patient, tumor, and treatment factors, a multivariable logistic regression model revealed increasing age, African-American race, Charlson-comorbidity index of >= 2, Medicaid insurance status, uninsured status, and Stage I disease were each independently associated with the lack of C-CRT. After adjusting for patient characteristics, low volume hospitals were noted to have overall significantly lower rates and greater variation in C-CRT administration. Patients in 'RT alone' group had an overall worse survival rate (adjusted-HR 1.47, 95%CI 1.4-1.56). Conclusion. Rates of C-CRT administration varied significantly across hospitals in the United States. Hospitals with a high case volume had higher rates and more consistent patterns of C-CRT administration. Furthermore, we identified independent factors, all of which represent noteworthy health disparities, associated with lower rates of C-CRT administration. (C) 2016 Elsevier Inc. All rights reserved. C1 [Uppal, Shitanshu; Reynolds, R. Kevin] Univ Michigan, Div Gynecol Oncol, Ann Arbor, MI 48109 USA. [del Carmen, Marcela G.; Bregar, Amy; Rauh-Hain, J. Alejandro] Harvard Med Sch, Massachusetts Gen Hosp, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA USA. [Rice, Laurel W.] Univ Wisconsin, Div Gynecol Oncol, Madison, WI USA. [Jolly, Shruti] Univ Michigan, Div Radiat Oncol, Ann Arbor, MI 48109 USA. [Uppal, Shitanshu; Abdelsattar, Zaid M.] Univ Michigan, Inst Healthcare Policy & Innovat, Ann Arbor, MI 48109 USA. RP Uppal, S (reprint author), Univ Michigan, 1500 E Med Dr, Ann Arbor, MI 48109 USA. EM uppal@med.umich.edu NR 29 TC 1 Z9 1 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD AUG PY 2016 VL 142 IS 2 BP 286 EP 292 DI 10.1016/j.ygyno.2016.05.026 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA DS4EH UT WOS:000380733700015 PM 27234144 ER PT J AU Lee, LJ Howitt, B Catalano, P Tanaka, C Murphy, R Cimbak, N DeMaria, R Bu, P Crum, C Horowitz, N Matulonis, U Viswanathan, AN AF Lee, Larissa J. Howitt, Brooke Catalano, Paul Tanaka, Cynthia Murphy, Rita Cimbak, Nicole DeMaria, Rebecca Bu, Paula Crum, Christopher Horowitz, Neil Matulonis, Ursula Viswanathan, Akila N. TI Prognostic importance of human papillomavirus (HPV) and p16 positivity in squamous cell carcinoma of the vulva treated with radiotherapy SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Vulvar cancer; Human papillomavirus; Radiotherapy; p16 ID INTRAEPITHELIAL NEOPLASIA; LICHEN-SCLEROSUS; P16(INK4A) EXPRESSION; OROPHARYNGEAL CANCER; IMPROVED SURVIVAL; CERVICAL-CANCER; HEAD; NECK; DNA; PREVALENCE AB Objective. HPV status is an important prognostic factor for patients with oropharyngeal, anal and cervical cancers treated with radiotherapy. This study evaluates the association between HPV and p16 status and outcome in a radiation-treated cohort with vulvar squamous cell carcinoma (SCC). Methods. Patients with vulvar SCC who received radiotherapy with or without surgical resection between 1985 and 2011 were identified retrospectively. Immunostaining for p16 and multiplex PCR for HPV genotyping were performed using archival tumor tissue from 57 patients. Actuarial estimates of PFS, OS and in-field recurrence were calculated using the Kaplan-Meier method. Cox proportional hazards models were used for multivariable analysis. Median follow-up was 58 months among the 57 patients with an available tumor specimen. Results. HPV prevalence was implied in 37% by (diffuse linear) p16 immunostaining and confirmed in 27% by HPV PCR with good agreement (K = 0.7). HPV-16 was identified in 80% of HPV-positive tumors. Women with p16-positive tumors had significantly higher 5-year PFS (65%,vs. 16%, p < 0.01) and OS (65% vs. 22%, p = 0.01) rates, as well as lower in-field relapse rates (19% vs. 75%, p < 0.01) compared to those with p16-negative disease. On multivariable analysis adjusted for age and stage, p16 positivity was significantly associated with better PFS (HR 0.4, 95% CI 0.2-0.9) and lower rates of in-field relapse (HR 0.2, 95% CI 0.06-0.6). Results were similar when analyzed by HPV DNA status. Conclusion. In this study, the presence of HPV or its surrogate of p16 immunostaining was an independent prognostic factor for in-field relapse and survival in women with vulvar SCC treated with radiotherapy. This finding warrants validation in larger cohorts or the prospective setting. (C) 2016 Elsevier Inc. All rights reserved. C1 [Lee, Larissa J.; Tanaka, Cynthia; Murphy, Rita; Cimbak, Nicole; DeMaria, Rebecca; Bu, Paula; Viswanathan, Akila N.] Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASBI-L2, Boston, MA 02115 USA. [Howitt, Brooke; Crum, Christopher] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Horowitz, Neil] Brigham & Womens Hosp, Dept Gynecol Oncol, 75 Francis St, Boston, MA 02115 USA. [Catalano, Paul] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Matulonis, Ursula] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Lee, Larissa J.; Howitt, Brooke; Catalano, Paul; Crum, Christopher; Horowitz, Neil; Matulonis, Ursula; Viswanathan, Akila N.] Harvard Med Sch, Boston, MA USA. RP Lee, LJ (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASBI-L2, Boston, MA 02115 USA. EM llee@lroc.harvard.edu FU Radiation Oncology Department at Brigham and Women's Hospital FX We would like to thank Barbara Silver for critical reading of this manuscript and the Radiation Oncology Department at Brigham and Women's Hospital for funding this work. NR 41 TC 2 Z9 2 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD AUG PY 2016 VL 142 IS 2 BP 293 EP 298 DI 10.1016/j.ygyno.2016.05.019 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA DS4EH UT WOS:000380733700016 PM 27210818 ER PT J AU Shah, R Foldyna, B Hoffmann, U AF Shah, R. Foldyna, B. Hoffmann, U. TI Outcomes of anatomical vs. functional testing for coronary artery disease Lessons from the PROMISE trial SO HERZ LA English DT Article DE Coronary artery disease; Coronary angiography; Computed tomography; Treatment outcome; Functional testing ID FRACTIONAL FLOW RESERVE; COMPUTED TOMOGRAPHIC ANGIOGRAPHY; ACUTE CHEST-PAIN; CT ANGIOGRAPHY; DIAGNOSTIC PERFORMANCE; MYOCARDIAL-ISCHEMIA; PROGNOSTIC VALUE; MEDICAL THERAPY; LEARNING-CURVE; CARDIAC EVENTS AB The development of coronary artery disease (CAD) is a major, final common pathway in heart disease worldwide. With a rise in stress testing and increased scrutiny on cost-effectiveness and radiation exposure in medical imaging, a focus on the relative merits of anatomic versus functional characterization of CAD has emerged. In this context, coronary computed tomography angiography (CCTA) is a noninvasive alternative to functional testing as a first-line test for CAD detection but is complimentary in its nature. Here, we discuss the design, results, and implications of the PROMISE trial, a randomized comparative effectiveness study of 10,003 patients across 193 sites in the United States and Canada comparing the prognostic and diagnostic power of CCTA and standard stress testing. Specifically, we discuss the safety (e. g., contrast, radiation exposure) of CCTA versus functional testing in CAD, the need for improved selection for noninvasive testing, the frequency of downstream testing after anatomic or functional imaging, the use of imaging results in clinical management, and novel modalities of CAD risk determination using CCTA. PROMISE demonstrated that in a real-world, low-to-intermediate risk patient population referred to noninvasive testing for CAD, both CCTA and functional testing approaches have similar clinical, economic, and safety-based outcomes. We conclude with open questions in CAD imaging, specifically as they pertain to the utilization of CCTA. C1 [Shah, R.; Foldyna, B.; Hoffmann, U.] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM uhoffmann@partners.org NR 35 TC 0 Z9 0 U1 0 U2 0 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0340-9937 EI 1615-6692 J9 HERZ JI Herz PD AUG PY 2016 VL 41 IS 5 BP 384 EP 390 DI 10.1007/s00059-016-4451-3 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DT3SA UT WOS:000381400000005 PM 27333988 ER PT J AU Tobyne, SM Boratyn, D Johnson, JA Greve, DN Mainero, C Klawiter, EC AF Tobyne, Sean M. Boratyn, Daria Johnson, Jessica A. Greve, Douglas N. Mainero, Caterina Klawiter, Eric C. TI A Surface-Based Technique for Mapping Homotopic Interhemispheric Connectivity: Development, Characterization, and Clinical Application SO HUMAN BRAIN MAPPING LA English DT Article DE functional connectivity; resting state; multiple sclerosis; corpus callosum; human ID INTRINSIC FUNCTIONAL CONNECTIVITY; CORPUS-CALLOSUM ATROPHY; HUMAN CEREBRAL-CORTEX; GRAY-MATTER ATROPHY; MULTIPLE-SCLEROSIS; HUMAN BRAIN; FIBER COMPOSITION; MAJOR DEPRESSION; MRI; FMRI AB The functional organization of the human brain consists of a high degree of connectivity between interhemispheric homologous regions. The degree of homotopic organization is known to vary across the cortex and homotopic connectivity is high in regions that share cross-hemisphere structural connections or are activated by common input streams (e.g., the visual system). Damage to one or both regions, as well as damage to the connections between homotopic regions, could disrupt this functional organization. Here were introduce and test a computationally efficient technique, surface-based homotopic interhermispheric connectivity (sHIC), that leverages surface-based registration and processing techniques in an attempt to improve the spatial specificity and accuracy of cortical interhemispheric connectivity estimated with resting state functional connectivity. This technique is shown to be reliable both within and across subjects. sHIC is also characterized in a dataset of nearly 1000 subjects. We confirm previous results showing increased interhemispheric connectivity in primary sensory regions, and reveal a novel rostro-caudal functionally defined network level pattern of sHIC across the brain. In addition, we demonstrate a structural-functional relationship between sHIC and atrophy of the corpus callosum in multiple sclerosis (r = 0.2979, p = 0.0461). sHIC presents as a sensitive and reliable measure of cortical homotopy that may prove useful as a biomarker in neurologic disease. (C) 2016 Wiley Periodicals, Inc. C1 [Tobyne, Sean M.; Boratyn, Daria; Klawiter, Eric C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Johnson, Jessica A.] Augustana Coll, Sioux Falls, SD USA. [Greve, Douglas N.; Mainero, Caterina] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. RP Tobyne, SM (reprint author), 149 13th St,Room 2503, Charlestown, MA 02129 USA. EM stobyne@nmr.mgh.har-vard.edu FU National Institutes of Health [K23NS078044-04, R01NS078322-01-A1]; National Multiple Sclerosis Society [PP1853] FX Contract grant sponsor: National Institutes of Health; Contract grant numbers: K23NS078044-04 and R01NS078322-01-A1; Contract grant sponsor: National Multiple Sclerosis Society; Contract grant number: PP1853 NR 77 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD AUG PY 2016 VL 37 IS 8 BP 2849 EP 2868 DI 10.1002/hbm.23214 PG 20 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA DU8UF UT WOS:000382490000009 PM 27219660 ER PT J AU Govani, SM Wiitala, WL Stidham, RW Saini, SD Hou, JK Feagins, LA Sussman, JB Higgins, PDR Waljee, AK AF Govani, Shail M. Wiitala, Wyndy L. Stidham, Ryan W. Saini, Sameer D. Hou, Jason K. Feagins, Linda A. Sussman, Jeremy B. Higgins, Peter D. R. Waljee, Akbar K. TI Age Disparities in the Use of Steroid-sparing Therapy for Inflammatory Bowel Disease SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE corticosteroids; elderly; escalation ID ULCERATIVE-COLITIS; RISK; EPIDEMIOLOGY; MANAGEMENT AB Background:Corticosteroids are effective rescue therapies for patients with inflammatory bowel disease (IBD), but have significant side effects, which may be amplified in the growing population of elderly patients with IBD. We aimed to compare the use of steroids and steroid-sparing therapies (immunomodulators and biologics) and rates of complications among elderly (65) and younger patients in a national cohort of veterans with IBD.Methods:We used national Veterans Health Administrative data to conduct a retrospective study of veterans with IBD between 2002 and 2010. Medications and the incidence of complications were obtained from the Veterans Health Administrative Decision Support Systems. Multivariate logistic regression accounting for facility-level clustering was used to identify predictors of use of steroid-sparing medications.Results:We identified 30,456 veterans with IBD. Of these, 94% were men and 40% were more than 65, and 32% were given steroids. Elderly veterans were less likely to receive steroids (23.8% versus 38.3%, P < 0.001) and were less likely to be prescribed steroid-sparing medications (25.5% versus 46.9%, respectively, P < 0.001). In multivariate analysis controlling for sex, age <65 (odds ratio, 2.19; 95% CI, 1.54-3.11) and gastroenterology care (odds ratio, 8.42; 95% CI, 6.18-11.47) were associated with initiation of steroid-sparing medications. After starting steroids, fracture rates increased in the elderly patients with IBD, whereas increases in venous thromboembolism and infections after starting steroids affected both age groups.Conclusions:Elderly veterans are less likely to receive steroids and steroid-sparing medications than younger veterans; elderly patients exposed to steroids were more likely to have fractures than the younger population. C1 [Govani, Shail M.; Stidham, Ryan W.; Saini, Sameer D.; Sussman, Jeremy B.; Higgins, Peter D. R.; Waljee, Akbar K.] Univ Michigan Hlth Syst, Dept Internal Med, Ann Arbor, MI USA. [Govani, Shail M.; Saini, Sameer D.] VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Wiitala, Wyndy L.; Sussman, Jeremy B.; Waljee, Akbar K.] VA Ctr Clin Management Res, Ann Arbor, MI USA. [Saini, Sameer D.; Sussman, Jeremy B.; Waljee, Akbar K.] Univ Michigan, Inst Healthcare Policy & Innovat, Ann Arbor, MI 48109 USA. [Hou, Jason K.] Houston VA HSR&D Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Hou, Jason K.] Baylor Coll Med, Dept Internal Med, Sect Gastroenterol & Hepatol, Houston, TX 77030 USA. [Feagins, Linda A.] Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, VA North Texas Hlth Care Syst, Div Gastroenterol & Hepatol, Dallas, TX USA. RP Govani, SM (reprint author), Dept Internal Med, 2215 Fuller Rd,Room 111D, Ann Arbor, MI 48105 USA. EM shailg@umich.edu FU VA HSR&D CDA-2 Career Development Award [1IK2HX000775]; VA HSR&D Center for Innovations in Quality, Effectiveness and Safety at the Michael E. DeBakey VA Medical Center, Houston, TX [CIN 13-413]; VA CDA [13-021] FX A. K. Waljee's research is funded by a VA HSR&D CDA-2 Career Development Award 1IK2HX000775. J. K. Hou's research is funded by the VA HSR&D Center for Innovations in Quality, Effectiveness and Safety (#CIN 13-413), at the Michael E. DeBakey VA Medical Center, Houston, TX. J. B. Sussman is supported by VA CDA 13-021. The sponsor had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. NR 21 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1078-0998 EI 1536-4844 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD AUG PY 2016 VL 22 IS 8 BP 1923 EP 1928 DI 10.1097/MIB.0000000000000817 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DT4TX UT WOS:000381475100019 PM 27416039 ER PT J AU DiNapoli, EA Bramoweth, AD Cinna, C Kasckow, J AF DiNapoli, Elizabeth A. Bramoweth, Adam D. Cinna, Christopher Kasckow, John TI Sedative hypnotic use among veterans with a newly reported mental health disorder SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Article DE sedatives and hypnotics; veterans; mental health; aged; inappropriate prescriptions ID INAPPROPRIATE MEDICATION USE; BENZODIAZEPINE USE; OLDER-ADULTS; ELDERLY VETERANS; PRIMARY-CARE; INSOMNIA; METAANALYSIS; COMMUNITY; PEOPLE; THERAPY AB Background: This study compared sedative hypnotic use by type of mental health diagnosis and determined factors associated with use among older veterans (65+ years) with a newly reported mental health disorder. Methods: This study used data from veterans who received primary care services at VA Pittsburgh Healthcare System (VAPHS) from January 1, 2007 to December 31, 2011 (n = 879). Results: Sedative hypnotics were commonly used in older veterans within 12-months following a newly reported mental health disorder (19.9%), particularly amongst those with insomnia (41.7%). The number of newly reported mental health disorders was a significant factor associated with sedative hypnotic use, with the odds of use increasing by more than 200% in older adults with two newly reported disorders compared to those with one newly reported mental health disorder. Conclusions: Continued efforts are needed to improve provider and patient awareness of the risks associated with sedative hypnotic use in older adults, as well as to increase access to and receipt of non-pharmacological mental health treatments for this vulnerable population. C1 [DiNapoli, Elizabeth A.; Bramoweth, Adam D.; Cinna, Christopher; Kasckow, John] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 4, Pittsburgh, PA USA. [DiNapoli, Elizabeth A.; Bramoweth, Adam D.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Cinna, Christopher] Duquesne Univ, Ctr Social & Publ Policy, Pittsburgh, PA 15219 USA. [Kasckow, John] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Kasckow, John] Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA USA. RP Bramoweth, AD (reprint author), VA Pittsburgh Healthcare Syst, Res Off Bldg 151R,Univ Dr, Pittsburgh, PA 15240 USA. EM Adam.Bramoweth@va.gov NR 33 TC 0 Z9 0 U1 2 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1041-6102 EI 1741-203X J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PD AUG PY 2016 VL 28 IS 8 BP 1391 EP 1398 DI 10.1017/S1041610216000521 PG 8 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA DU7IV UT WOS:000382388300017 PM 27073116 ER PT J AU Wachterman, MW Pilver, C Smith, D Ersek, M Lipsitz, SR Keating, NL AF Wachterman, Melissa W. Pilver, Corey Smith, Dawn Ersek, Mary Lipsitz, Stuart R. Keating, Nancy L. TI Quality of End-of-Life Care Provided to Patients With Different Serious Illnesses SO JAMA INTERNAL MEDICINE LA English DT Article ID NURSING-HOME RESIDENTS; PALLIATIVE CARE; VETERANS-AFFAIRS; FAMILY-MEMBERS; INTENSIVE-CARE; HOSPITALIZED-PATIENTS; POSTTRAUMATIC-STRESS; ADVANCED DEMENTIA; CANCER; DEATH AB IMPORTANCE Efforts to improve end-of-life care have focused primarily on patients with cancer. High-quality end-of-life care is also critical for patients with other illnesses. OBJECTIVE To compare patterns of end-of-life care and family-rated quality of care for patients dying with different serious illnesses. DESIGN, SETTING, AND PARTICIPANTS A retrospective cross-sectional study was conducted in all 146 inpatient facilities within the Veteran Affairs health system among patients who died in inpatient facilities between October 1, 2009, and September 30, 2012, with clinical diagnoses categorized as end-stage renal disease (ESRD), cancer, cardiopulmonary failure (congestive heart failure or chronic obstructive pulmonary disease), dementia, frailty, or other conditions. Data analysis was conducted from April 1, 2014, to February 10, 2016. MAIN OUTCOMES AND MEASURES Palliative care consultations, do-not- resuscitate orders, death in inpatient hospices, death in the intensive care unit, and family-reported quality of end-of-life care. RESULTS Among 57 753 decedents, approximately half of the patients with ESRD, cardiopulmonary failure, or frailty received palliative care consultations (adjusted proportions, 50.4%, 46.7%, and 43.7%, respectively) vs 73.5% of patients with cancer and 61.4% of patients with dementia (P < .001). Approximately one-third of patients with ESRD, cardiopulmonary failure, or frailty (adjusted proportions, 32.3%, 34.1%, and 35.2%, respectively) died in the intensive care unit, more than double the rates among patients with cancer and those with dementia (13.4% and 8.9%, respectively) (P < .001). Rates of excellent quality of end-of-life care reported by 34 005 decedents' families were similar for patients with cancer and those with dementia (adjusted proportions, 59.2% and 59.3%; P = .61), but lower for patients with ESRD, cardiopulmonary failure, or frailty (54.8%, 54.8%, and 53.7%, respectively; all P <= .02 vs patients with cancer). This quality advantage was mediated by palliative care consultation, setting of death, and a code status of do-not- resuscitate; adjustment for these variables rendered the association between diagnosis and overall end-of-life care quality nonsignificant. CONCLUSIONS AND RELEVANCE Family-reported quality of end-of-life care was significantly better for patients with cancer and those with dementia than for patients with ESRD, cardiopulmonary failure, or frailty, largely owing to higher rates of palliative care consultation and do-not- resuscitate orders and fewer deaths in the intensive care unit among patients with cancer and those with dementia. Increasing access to palliative care and goals of care discussions that address code status and preferred setting of death, particularly for patients with end-organ failure and frailty, may improve the overall quality of end-of-life care for Americans dying of these illnesses. C1 [Wachterman, Melissa W.] VA Boston Healthcare Syst, Gen Internal Med Sect, 150 S Huntington Ave,Bldg 9, Boston, MA 02130 USA. [Wachterman, Melissa W.; Lipsitz, Stuart R.; Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, 75 Francis St, Boston, MA 02115 USA. [Wachterman, Melissa W.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Pilver, Corey] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA USA. [Smith, Dawn; Ersek, Mary] Dept Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. [Ersek, Mary] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Keating, Nancy L.] Harvard Med Sch, Dept Hlth Care Policy, Boston, MA USA. RP Wachterman, MW (reprint author), VA Boston Healthcare Syst, Gen Internal Med Sect, 150 S Huntington Ave,Bldg 9, Boston, MA 02130 USA. EM mwachterman@partners.org FU National Palliative Care Research Center Junior Faculty Career Development Award; National Institute on Aging [1K23AG049088-01A1]; Department of Veterans Affairs, Veterans Health Administration FX Dr Wachterman received support from the National Palliative Care Research Center Junior Faculty Career Development Award, from grant 1K23AG049088-01A1 from the National Institute on Aging, and from the Department of Veterans Affairs, Veterans Health Administration. NR 47 TC 13 Z9 13 U1 17 U2 17 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD AUG PY 2016 VL 176 IS 8 BP 1095 EP 1102 DI 10.1001/jamainternmed.2016.1200 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA DT0AN UT WOS:000381145000017 PM 27367547 ER PT J AU Fischer, SM Bekelman, D Bailey, FA AF Fischer, Stacy M. Bekelman, David Bailey, F. Amos TI Family Assessment of Quality of Care in the Last Month of Life SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID PALLIATIVE CARE; END C1 [Fischer, Stacy M.; Bekelman, David; Bailey, F. Amos] Univ Colorado, Div Gen Internal Med, Dept Med, Sch Med, Anschutz Med Campus,Mail Stop B180, Aurora, CO 80045 USA. [Bekelman, David] Eastern Colorado Hlth Care Syst, Div Geriatr, Dept Internal Med, Dept Vet Affairs, Denver, CO USA. [Bailey, F. Amos] Birmingham VA Med Ctr, Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Birmingham, AL USA. RP Bailey, FA (reprint author), Univ Colorado, Div Gen Internal Med, Dept Med, Sch Med, Anschutz Med Campus,Mail Stop B180, Aurora, CO 80045 USA. EM amos.bailey@ucdenver.edu NR 5 TC 0 Z9 0 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD AUG PY 2016 VL 176 IS 8 BP 1102 EP 1104 DI 10.1001/jamainternmed.2016.1208 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA DT0AN UT WOS:000381145000018 PM 27367457 ER PT J AU Chen-Scarabelli, C Scarabelli, TM AF Chen-Scarabelli, Carol Scarabelli, Tiziano M. TI Syncope While Driving in Denmark SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Chen-Scarabelli, Carol; Scarabelli, Tiziano M.] Birmingham VA Med Ctr, 700 S 19th St, Birmingham, AL 35233 USA. [Scarabelli, Tiziano M.] Univ Alabama Birmingham, Med Ctr, Birmingham, AL USA. RP Chen-Scarabelli, C (reprint author), Birmingham VA Med Ctr, 700 S 19th St, Birmingham, AL 35233 USA. EM chenscarabelli@hotmail.com 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 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD AUG PY 2016 VL 176 IS 8 BP 1230 EP 1230 DI 10.1001/jamainternmed.2016.3723 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA DT0AN UT WOS:000381145000051 PM 27479671 ER PT J AU LeBovidge, JS Elverson, W Timmons, KG Hawryluk, EB Rea, C Lee, M Schneider, LC AF LeBovidge, Jennifer S. Elverson, Wendy Timmons, Karol G. Hawryluk, Elena B. Rea, Corinna Lee, Margaret Schneider, Lynda C. TI Multidisciplinary interventions in the management of atopic dermatitis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE Atopic dermatitis; eczema; multidisciplinary; education; treatment; quality of life; psychology; nutrition; nursing ID THERAPEUTIC PATIENT EDUCATION; RANDOMIZED CONTROLLED-TRIAL; VITAMIN-D DEFICIENCY; COWS MILK ALLERGY; QUALITY-OF-LIFE; YOUNG-CHILDREN; FOOD ALLERGY; CLINICAL MANAGEMENT; INITIAL VALIDATION; TRAINING-PROGRAM AB Atopic dermatitis (AD) is the most common pediatric skin disease. AD has a significant effect on patient and family quality of life caused by intense pruritus, sleep disruption, dietary and nutritional concerns, and psychological stress associated with the disease and its management. Multidisciplinary approaches to AD care have been developed in appreciation of the complex interplay among biological, psychological, behavioral, and dietary factors that affect disease control and the wide range of knowledge, skills, and support that patients and families require to effectively manage and cope with this condition. Common components of multidisciplinary treatment approaches include medical evaluation and management by an AD specialist, education and nursing care, psychological and behavioral support, and nutritional assessment and guidance. Models of care include both clinical programs and structured educational groups provided as adjuncts to standard clinical care. Available evidence suggests beneficial effects of multidisciplinary interventions in improving disease severity and quality of life, particularly for patients with moderate-to-severe disease. Additional research is needed to identify the best candidates for the various multidisciplinary approaches and evaluate the cost-effectiveness of these programs. C1 [LeBovidge, Jennifer S.; Timmons, Karol G.; Schneider, Lynda C.] Boston Childrens Hosp, Div Immunol, Allergy Program, Boston, MA USA. [Elverson, Wendy] Boston Childrens Hosp, Div Gastroenterol Hepatol & Nutr, Ctr Nutr, Boston, MA USA. [Hawryluk, Elena B.; Lee, Margaret] Boston Childrens Hosp, Div Immunol, Dermatol Program, Boston, MA USA. [Rea, Corinna] Boston Childrens Hosp, Dept Med, Div Gen Pediat, Boston, MA USA. [LeBovidge, Jennifer S.; Hawryluk, Elena B.; Rea, Corinna; Schneider, Lynda C.] Harvard Med Sch, Boston, MA USA. [Hawryluk, Elena B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Lee, Margaret] Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02215 USA. RP LeBovidge, JS (reprint author), Boston Childrens Hosp, Div Immunol, Fegan 6,300 Longwood Ave, Boston, MA 02115 USA. EM jennifer.lebovidge@childrens.harvard.edu FU APGNN FX J. S. LeBovidge is a member of National Eczema Association Workgroup. W. Elverson has received lecture fees from APGNN. L. C. Schneider is on the National Eczema Association Scientific Advisory Board. The rest of the authors declare that they have no relevant conflicts of interest. NR 97 TC 2 Z9 2 U1 9 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD AUG PY 2016 VL 138 IS 2 BP 325 EP 334 DI 10.1016/j.jaci.2016.04.003 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA DS5PY UT WOS:000380835800001 PM 27497275 ER PT J AU Zgierska, AE Burzinski, CA Cox, J Kloke, J Singles, J Mirgain, S Stegner, A Cook, DB Backonja, M AF Zgierska, Aleksandra E. Burzinski, Cindy A. Cox, Jennifer Kloke, John Singles, Janice Mirgain, Shilagh Stegner, Aaron Cook, Dane B. Backonja, Miroslav TI Mindfulness Meditation-Based Intervention Is Feasible, Acceptable, and Safe for Chronic Low Back Pain Requiring Long-Term Daily Opioid Therapy SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID CHRONIC NONCANCER PAIN; 3-YEAR FOLLOW-UP; PRIMARY-CARE; STRESS REDUCTION; GUIDELINES; TRIALS; MODEL AB Objective: Although mindfulness meditation (MM) is increasingly used for chronic pain treatment, limited evidence supports its clinical application for opioid-treated chronic low back pain (CLBP). The goal of this study was to determine feasibility, acceptability, and safety of an MM-based intervention in patients with CLBP requiring daily opioid therapy. Design: 26-week pilot randomized controlled trial comparing MM-based intervention, combined with usual care, to usual care alone. Setting: Outpatient. Patients: Adults with CLBP treated with >= 30 mg of morphine-equivalent dose (MED) per day for 3 months or longer. Interventions: Targeted MM-based intervention consisted of eight weekly 2-hour group sessions and home practice (30 minutes/d, 6 days/wk) during the study. "Usual care'' for opioid-treated CLBP was provided to participants by their regular clinicians. Outcome measures: Feasibility and acceptability of the MM intervention were assessed by adherence to intervention protocol and treatment satisfaction among experimental participants. Safety was evaluated by inquiry about side effects/adverse events and opioid dose among all study participants. Results: Thirty-five participants enrolled during the 10-week recruitment period. The mean age (+/- standard deviation) was 51.8 +/- 9.7 years; the patients were predominantly female, with substantial CLBP-related pain and disability, and treated with 148.3 +/- 129.2mg of MED per day. All participants completed baseline assessments; none missed both follow-up assessments or withdrew. Among experimental participants (n = 21), 19 attended 1 or more intervention sessions and 14 attended 4 or more. They reported, on average, 164.0 +/- 122.1 minutes of formal practice per week during the 26-week study and 103.5 +/- 111.5 minutes of brief, informal practice per week. Seventeen patients evaluated the intervention, indicating satisfaction; their qualitative responses described the course as useful for pain management (n = 10) and for improving pain coping skills (n = 8). No serious adverse events or safety concerns occurred among the study participants. Conclusions: MM-based intervention is feasible, acceptable, and safe in opioid-treated CLBP. C1 [Zgierska, Aleksandra E.; Burzinski, Cindy A.; Cox, Jennifer] Univ Wisconsin, Sch Med & Publ Hlth, Dept Family Med & Community Hlth, 1100 Delaplaine Court, Madison, WI 53715 USA. [Kloke, John] Univ Wisconsin, Sch Med & Publ Hlth, Dept Biostat & Med Informat, Madison, WI USA. [Singles, Janice; Mirgain, Shilagh] Univ Wisconsin, Sch Med & Publ Hlth, Dept Orthoped & Rehabil, Madison, WI USA. [Stegner, Aaron; Cook, Dane B.] William S Middleton Mem Vet Adm Med Ctr, Res Serv, Madison, WI USA. [Stegner, Aaron; Cook, Dane B.] Univ Wisconsin, Sch Educ, Dept Kinesiol, Madison, WI USA. [Backonja, Miroslav] Univ Wisconsin, Dept Neurol, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Backonja, Miroslav] PRAHS Clin Res Co Lifetree, Salt Lake City, UT USA. RP Zgierska, AE (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Family Med & Community Hlth, 1100 Delaplaine Court, Madison, WI 53715 USA. EM Aleksandra.Zgierska@fammed.wisc.edu FU National Institutes of Health (NIH) National Institute on Alcohol Abuse and Alcoholism [K23AA017508]; University of Wisconsin-Madison; NIH National Center for Advancing Translational Sciences [UL1TR000427] FX The study is registered on ClinicalTrials.gov (NCT01775995). Dr. Zgierska's work was supported by the K23AA017508 award from the National Institutes of Health (NIH) National Institute on Alcohol Abuse and Alcoholism and by funds from the University of Wisconsin-Madison. The project was also supported by the Clinical and Translational Science Award program through the NIH National Center for Advancing Translational Sciences, grant UL1TR000427. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 51 TC 1 Z9 1 U1 9 U2 9 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 EI 1557-7708 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD AUG PY 2016 VL 22 IS 8 BP 610 EP 620 DI 10.1089/acm.2015.0314 PG 11 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA DU6AA UT WOS:000382293700006 PM 27267151 ER PT J AU Mills, PJ Wilson, KL Pung, MA Weiss, L Patel, S Doraiswamy, PM Peterson, CT Porter, V Schadt, E Chopra, D Tanzi, RE AF Mills, Paul J. Wilson, Kathleen L. Pung, Meredith A. Weiss, Lizabeth Patel, Sheila Doraiswamy, P. Murali Peterson, Christine Tara Porter, Valencia Schadt, Eric Chopra, Deepak Tanzi, Rudolph E. TI The Self-Directed Biological Transformation Initiative and Well-Being SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; HEALTH-CARE PRACTITIONERS; HEART-FAILURE PATIENTS; POSITIVE PSYCHOLOGY; OLDER-ADULTS; CANCER-PATIENTS; MENTAL-HEALTH; DOUBLE-BLIND; INTERVENTIONS; GRATITUDE AB Objective: To examine the effects of a comprehensive residential mind-body program on well-being. Design: The Self-Directed Biological Transformation Initiative was a quasi-randomized trial comparing the effects of participation in a 6-day Ayurvedic system of medicine-based comprehensive residential program with a 6-day residential vacation at the same retreat location. Setting: Retreat setting. Participants: 69 healthy women (n = 58) and men (n = 11) (mean age +/- standard deviation, 53.6 +/- 12 years). Intervention: The Ayurvedic intervention addressed physical and emotional well-being through group meditation and yoga, massage, diet, adaptogenic herbs, lectures, and journaling. Outcome measures: A battery of standardized questionnaires. Results: Participants in the Ayurvedic program showed significant and sustained increases in ratings of spirituality (p < 0.01) and gratitude (p < 0.05) compared with the vacation group, which showed no change. The Ayurvedic participants also showed increased ratings for self-compassion (p < 0.01) as well as less anxiety at the 1-month follow-up (p < 0.05). Conclusions: Findings suggest that a short-term intensive program providing holistic instruction and experience in mind-body healing practices can lead to significant and sustained increases in perceived well-being and that relaxation alone is not enough to improve certain aspects of well-being. C1 [Mills, Paul J.; Wilson, Kathleen L.; Pung, Meredith A.; Patel, Sheila; Peterson, Christine Tara; Porter, Valencia; Chopra, Deepak] Univ Calif San Diego, Dept Family Med & Publ Hlth, 9500 Gilman Dr, La Jolla, CA 92093 USA. [Mills, Paul J.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Mills, Paul J.] Samueli Inst, Alexandria, VA USA. [Weiss, Lizabeth; Patel, Sheila; Peterson, Christine Tara; Porter, Valencia; Chopra, Deepak] Chopra Ctr Wellbeing, Carlsbad, CA USA. [Doraiswamy, P. Murali] Duke Univ, Duke Inst Brain Sci, Durham, NC USA. [Schadt, Eric] Mt Sinai Hosp, Genet & Genom Sci, New York, NY 10029 USA. [Tanzi, Rudolph E.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. RP Mills, PJ (reprint author), Univ Calif San Diego, Dept Family Med & Publ Hlth, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM pmills@ucsd.edu FU Fred Foundation; MCJ Amelior Foundation; National Philanthropic Trust; Walton Family Foundation; Chopra Foundation FX Supported by the Fred Foundation, the MCJ Amelior Foundation, the National Philanthropic Trust, the Walton Family Foundation, and the Chopra Foundation. NR 71 TC 1 Z9 1 U1 18 U2 18 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 EI 1557-7708 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD AUG PY 2016 VL 22 IS 8 BP 627 EP 634 DI 10.1089/acm.2016.0002 PG 8 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA DU6AA UT WOS:000382293700008 PM 27351443 ER PT J AU Kumari, M Wang, X Lantier, L Lyubetskaya, A Eguchi, J Kang, S Tenen, D Roh, HC Kong, XX Kazak, L Ahmad, R Rosen, ED AF Kumari, Manju Wang, Xun Lantier, Louise Lyubetskaya, Anna Eguchi, Jun Kang, Sona Tenen, Danielle Roh, Hyun Cheol Kong, Xingxing Kazak, Lawrence Ahmad, Rasheed Rosen, Evan D. TI IRF3 promotes adipose inflammation and insulin resistance and represses browning SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NF-KAPPA-B; ENDOPLASMIC-RETICULUM STRESS; GENE-EXPRESSION DATA; IMMUNE-SYSTEM; IKK-EPSILON; ADAPTIVE THERMOGENESIS; TRANSCRIPTION FACTORS; EPIGENOMIC ANALYSIS; MASTER REGULATORS; OBESE MICE AB The chronic inflammatory state that accompanies obesity is a major contributor to insulin resistance and other dysfunctional adaptations in adipose tissue. Cellular and secreted factors promote the inflammatory milieu of obesity, but the transcriptional pathways that drive these processes are not well described. Although the canonical inflammatory transcription factor NF-kappa B is considered to be the major driver of adipocyte inflammation, members of the interferon regulatory factor (IRF) family may also play a role in this process. Here, we determined that IRF3 expression is upregulated in the adipocytes of obese mice and humans. Signaling through TLR3 and TLR4, which lie upstream of IRF3, induced insulin resistance in murine adipocytes, while IRF3 knockdown prevented insulin resistance. Furthermore, improved insulin sensitivity in IRF3-deficient mice was associated with reductions in intra-adipose and systemic inflammation in the high fat-fed state, enhanced browning of subcutaneous fat, and increased adipose expression of GLUT4. Taken together, the data indicate that IRF3 is a major transcriptional regulator of adipose inflammation and is involved in maintaining systemic glucose and energy homeostasis. C1 [Kumari, Manju; Wang, Xun; Lyubetskaya, Anna; Kang, Sona; Tenen, Danielle; Roh, Hyun Cheol; Kong, Xingxing; Rosen, Evan D.] Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA. [Lantier, Louise] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. [Eguchi, Jun] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Nephrol Rheumatol Endocrinol & Metab, Okayama, Japan. [Kazak, Lawrence] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. [Kazak, Lawrence] Harvard Med Sch, Dept Cell Biol, Boston, MA USA. [Ahmad, Rasheed] Dasman Diabet Inst, Immunol & Innovat Cell Therapy Unit, Kuwait, Kuwait. RP Rosen, ED (reprint author), Harvard Med Sch, Beth Israel Deaconess Med Ctr, 330 Brookline Ave,E-CLS743, Boston, MA 02215 USA. EM erosen@bidmc.harvard.edu RI Lyubetskaya, Anna/A-6290-2017 FU NIH [R01 DK085171, DK102170]; Dasman Diabetes Institute; Kuwait Foundation FX This work was funded by NIH R01 DK085171 and DK102170 to E.D. Rosen, and by funds from the Dasman Diabetes Institute and the Kuwait Foundation for the Advancement of Sciences. We thank Ines Sousa Lima for assistance in insulin signaling studies. Eleanna DeFilippis, Linus Tsai, and Su Xu provided technical support and helpful discussions. Valerie Atizado and Puthiyaveetil Shihab helped with IHC and qRT-PCR of human samples, respectively. We also thank the Vanderbilt Mouse Metabolic Phenotyping Center (DK059637) for performing the hyperinsulinemic-euglycemic clamps. The Vanderbilt University Hormone Assay and Analytical Core performed the hormone analysis (DK059637 and DK020593). NR 61 TC 6 Z9 6 U1 4 U2 4 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 AUG 1 PY 2016 VL 126 IS 8 BP 2839 EP 2854 DI 10.1172/JCI86080 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DU1BZ UT WOS:000381943000010 PM 27400129 ER PT J AU Yu, J Storer, BE Kushekhar, K Abu Zaid, M Zhang, Q Gafken, PR Ogata, Y Martin, PJ Flowers, ME Hansen, JA Arora, M Cutler, C Jagasia, M Pidala, J Hamilton, BK Chen, GL Pusic, I Lee, SJ Paczesny, S AF Yu, Jeffrey Storer, Barry E. Kushekhar, Kushi Abu Zaid, Mohammad Zhang, Qing Gafken, Philip R. Ogata, Yuko Martin, Paul J. Flowers, Mary E. Hansen, John A. Arora, Mukta Cutler, Corey Jagasia, Madan Pidala, Joseph Hamilton, Betty K. Chen, George L. Pusic, Iskra Lee, Stephanie J. Paczesny, Sophie TI Biomarker Panel for Chronic Graft-Versus-Host Disease SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; BLOOD STEM-CELLS; CLINICAL-TRIALS; CHRONIC GVHD; BONE-MARROW; T-CELLS; RISK-FACTORS; TRANSPLANTATION; CRITERIA AB Purpose To identify diagnostic and prognostic markers of chronic graft-versus-host disease (cGVHD), the major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Patients and Methods Using a quantitative proteomics approach, we compared pooled plasma samples obtained at matched time points after HCT (median, 103 days) from 35 patients with cGVHD and 18 without cGVHD (data are available via ProteomeXchange with identifier PXD002762). Of 105 proteins showing at least a 1.25-fold difference in expression, 22 were selected on the basis of involvement in relevant pathways and enzyme-linked immunosorbent assay availability. Chemokine (C-X-C motif) ligand 9 (CXCL9) and suppression of tumorigenicity 2 (ST2) also were measured on the basis of previously determined associations with GVHD. Concentrations of the four lead biomarkers were measured at or after diagnosis in plasma from two independent verification cohorts (n = 391) to determine their association with cGVHD. Their prognostic ability when measured at approximately day + 100 after HCT was evaluated in plasma of a second verification cohort (n = 172). Results Of 24 proteins measured in the first verification cohort, nine proteins were associated with cGVHD, and only four (ST2, CXCL9, matrix metalloproteinase 3, and osteopontin) were necessary to compose a four-biomarker panel with an area under the receiver operating characteristic curve (AUC) of 0.89 and significant correlation with cGVHD diagnosis, cGVHD severity, and nonrelapse mortality. In a second verification cohort, this panel distinguished patients with cGVHD (AUC, 0.75), and finally, the panel measured at day + 100 could predict cGVHD occurring within the next 3 months with an AUC of 0.67 and 0.79 without and with known clinical risk factors, respectively. Conclusion We conclude that the biomarker panel measured at diagnosis or day + 100 after HCT may allow patient stratification according to risk of cGVHD. (C) 2016 by American Society of Clinical Oncology (C) 2016 by American Society of Clinical Oncology C1 [Yu, Jeffrey; Kushekhar, Kushi; Abu Zaid, Mohammad; Paczesny, Sophie] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Storer, Barry E.; Zhang, Qing; Gafken, Philip R.; Ogata, Yuko; Martin, Paul J.; Flowers, Mary E.; Hansen, John A.; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Storer, Barry E.] Univ Washington, Sch Med, Seattle, WA USA. [Arora, Mukta] Univ Minnesota, Minneapolis, MN USA. [Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jagasia, Madan] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA. [Pidala, Joseph] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Hamilton, Betty K.] Cleveland Clin Fdn, 9500 Euclid Ave, Cleveland, OH 44195 USA. [Chen, George L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Pusic, Iskra] Washington Univ, Sch Med, St Louis, MO USA. RP Paczesny, S (reprint author), Indiana Univ Sch Med, Dept Pediat, Wells Ctr Pediat Res, Melvin & Bren Simon Canc Ctr, 1044 W Walnut St,Room 425, Indianapolis, IN 46204 USA.; Paczesny, S (reprint author), Indiana Univ Sch Med, Dept Immunol, Wells Ctr Pediat Res, Melvin & Bren Simon Canc Ctr, 1044 W Walnut St,Room 425, Indianapolis, IN 46204 USA. EM sophpacz@iu.edu FU National Marrow Donor Program through the Amy Strelzer Manasevit Scholar Grant [200513]; National Institutes of Health (NIH) [R01CA174667, R01CA118953, U54CA163438]; National Center for Advancing Translational Science (NCATS) Rare Diseases Clinical Research Network (RDCRN) [U54 CA163438]; Cancer Center Support Grant from the NIH [P30 CA015704]; Office of Rare Disease Research, NCATS FX Supported by the National Marrow Donor Program through the Amy Strelzer Manasevit Scholar Grant No. 200513 (S.P.) and National Institutes of Health (NIH) Grants No. R01CA174667 (S.P.), R01CA118953 (S.J.L.), and U54CA163438 (S.J.L.). The Chronic Graft-Versus-Host Disease Consortium (Grant No. U54 CA163438) is part of the National Center for Advancing Translational Science (NCATS) Rare Diseases Clinical Research Network (RDCRN). RDCRN is an initiative of the Office of Rare Disease Research, NCATS, funded through a collaboration between NCATS and the National Cancer Institute. The Fred Hutchinson Cancer Research Center Proteomics Facility is partially funded by Cancer Center Support Grant No. P30 CA015704 from the NIH. NR 31 TC 7 Z9 7 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 AUG 1 PY 2016 VL 34 IS 22 BP 2583 EP U57 DI 10.1200/JCO.2015.65.9615 PG 10 WC Oncology SC Oncology GA DU8LQ UT WOS:000382465300006 PM 27217465 ER PT J AU Dickler, MN Barry, WT Cirrincione, CT Ellis, MJ Moynahan, ME Innocenti, F Hurria, A Rugo, HS Lake, DE Hahn, O Schneider, BP Tripathy, D Carey, LA Winer, EP Hudis, CA AF Dickler, Maura N. Barry, William T. Cirrincione, Constance T. Ellis, Matthew J. Moynahan, Mary Ellen Innocenti, Federico Hurria, Arti Rugo, Hope S. Lake, Diana E. Hahn, Olwen Schneider, Bryan P. Tripathy, Debasish Carey, Lisa A. Winer, Eric P. Hudis, Clifford A. TI Phase III Trial Evaluating Letrozole As First-Line Endocrine Therapy With or Without Bevacizumab for the Treatment of Postmenopausal Women With Hormone Receptor-Positive Advanced-Stage Breast Cancer: CALGB 40503 (Alliance) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; FIRST-LINE THERAPY; ADJUVANT BEVACIZUMAB; FACTOR EXPRESSION; PLUS BEVACIZUMAB; RANDOMIZED-TRIAL; DOUBLE-BLIND; ESTROGEN; TAMOXIFEN; COMBINATION AB Purpose To investigate whether anti-vascular endothelial growth factor therapy with bevacizumab prolongs progression-free survival (PFS) when added to first-line letrozole as treatment of hormone receptor-positive metastatic breast cancer (MBC). Patients and Methods Women with hormone receptor-positive MBC were randomly assigned 1:1 in a multicenter, openlabel, phase III trial of letrozole (2.5 mg orally per day) with or without bevacizumab (15 mg/kg intravenously once every 3 weeks) within strata defined by measurable disease and disease-free interval. This trial had 90% power to detect a 50% improvement in median PFS from 6 to 9 months. Using a one-sided alpha = .025, a target sample size of 352 patients was planned. Results From May 2008 to November 2011, 350 women were recruited; 343 received treatment and were observed for efficacy and safety. Median age was 58 years (range, 25 to 87 years). Sixty-two percent had measurable disease, and 45% had de novo MBC. At a median follow-up of 39 months, the addition of bevacizumab resulted in a significant reduction in the hazard of progression (hazard ratio, 0.75; 95% CI, 0.59 to 0.96; P = .016) and a prolongation in median PFS from 15.6 months with letrozole to 20.2 months with letrozole plus bevacizumab. There was no significant difference in overall survival (hazard ratio, 0.87; 95% CI, 0.65 to 1.18; P = .188), with median overall survival of 43.9 months with letrozole versus 47.2 months with letrozole plus bevacizumab. The largest increases in incidence of grade 3 to 4 treatment-related toxicities with the addition of bevacizumab were hypertension (24% v2%) and proteinuria (11% v 0%). Conclusion The addition of bevacizumab to letrozole improved PFS in hormone receptor-positive MBC, but this benefit was associated with a markedly increased risk of grade 3 to 4 toxicities. Research on predictive markers will be required to clarify the role of bevacizumab in this setting. (C) 2016 by American Society of Clinical Oncology (C) 2016 by American Society of Clinical Oncology C1 [Dickler, Maura N.; Moynahan, Mary Ellen; Lake, Diana E.; Hudis, Clifford A.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Barry, William T.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Winer, Eric P.] Dana Farber Partners Canc Care, Boston, MA USA. [Cirrincione, Constance T.] Duke Univ, Durham, NC USA. [Ellis, Matthew J.] Baylor Coll Med, Houston, TX 77030 USA. [Tripathy, Debasish] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Innocenti, Federico; Carey, Lisa A.] Univ N Carolina, Chapel Hill, NC USA. [Hurria, Arti] City Hope Natl Med Ctr, Duarte, CA USA. [Rugo, Hope S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hahn, Olwen] Alliance Clin Trials Oncol, Chicago, IL USA. [Schneider, Bryan P.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. RP Dickler, MN (reprint author), Mem Sloan Kettering Canc Ctr, Weill Cornell Med Ctr, Breast Med Serv, 300 East 66th St, New York, NY 10065 USA. EM dicklerm@mskcc.org FU National Cancer Institute [U10CA031946, U10CA033601, U10CA180821, U10CA180882]; Genentech; Novartis (letrozole); Memorial Sloan Kettering Cancer Center [P30 CA008748]; Genentech (bevacizumab); [U10CA138561]; [U10CA180791]; [U10CA180795]; [U10CA180820]; [U10CA180838]; [U10CA180858]; [U10CA180867]; [U10CA180888] FX Supported by National Cancer Institute Awards No. U10CA031946, U10CA033601, U10CA180821, and U10CA180882 (to the Alliance for Clinical Trials in Oncology); and in part by Grants No. U10CA138561, U10CA180791, U10CA180795, U10CA180820, U10CA180838, U10CA180858, U10CA180867, and U10CA180888; by Genentech (research funding and bevacizumab) and Novartis (letrozole); and by Core Grant No. P30 CA008748 from Memorial Sloan Kettering Cancer Center. NR 51 TC 4 Z9 4 U1 8 U2 8 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 AUG 1 PY 2016 VL 34 IS 22 BP 2602 EP U86 DI 10.1200/JCO.2015.66.1595 PG 11 WC Oncology SC Oncology GA DU8LQ UT WOS:000382465300008 PM 27138575 ER PT J AU McCarthy, AM Bristol, M Domchek, SM Groeneveld, PW Kim, Y Motanya, UN Shea, JA Armstrong, K AF McCarthy, Anne Marie Bristol, Mirar Domchek, Susan M. Groeneveld, Peter W. Kim, Younji Motanya, U. Nkiru Shea, Judy A. Armstrong, Katrina TI Health Care Segregation, Physician Recommendation, and Racial Disparities in BRCA1/2 Testing Among Women With Breast Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; AFRICAN-AMERICAN WOMEN; TASK-FORCE RECOMMENDATION; LOCALIZED PROSTATE-CANCER; US NURSING-HOMES; RESIDENTIAL SEGREGATION; RISK-ASSESSMENT; PRECISION MEDICINE; FAMILY-HISTORY; OVARIAN-CANCER AB Purpose Racial disparities in BRCA1/2 testing have been documented, but causes of these disparities are poorly understood. The study objective was to investigate whether the distribution of black and white patients across cancer providers contributes to disparities in BRCA1/2 testing. Patients and Methods We conducted a population-based study of women in Pennsylvania and Florida who were 18 to 64 years old and diagnosed with invasive breast cancer between 2007 and 2009, linking cancer registry data, the American Medical Association Physician Masterfile, and patient and physician surveys. The study included 3,016 women (69% white, 31% black), 808 medical oncologists, and 732 surgeons. Results Black women were less likely to undergo BRCA1/2 testing than white women (odds ratio [OR], 0.40; 95% CI, 0.34 to 0.48; P < .001). This difference was attenuated but not eliminated by adjustment for mutation risk, clinical factors, sociodemographic characteristics, and attitudes about testing (OR, 0.66; 95% CI, 0.53 to 0.81; P < .001). The care of black and white women was highly segregated across surgeons and oncologists (index of dissimilarity 64.1 and 61.9, respectively), but adjusting for clustering within physician or physician characteristics did not change the size of the testing disparity. Black women were less likely to report that they had received physician recommendation for BRCA1/2 testing even after adjusting for mutation risk (OR, 0.66; 95% CI, 0.54 to 0.82; P,.001). Adjusting for physician recommendation further attenuated the testing disparity (OR, 0.76; 95% CI, 0.57 to 1.02; P = .06). Conclusion Although black and white patients with breast cancer tend to see different surgeons and oncologists, this distribution does not contribute to disparities in BRCA1/2 testing. Instead, residual racial differences in testing after accounting for patient and physician characteristics are largely attributable to differences in physician recommendations. Efforts to address these disparities should focus on ensuring equity in testing recommendations. (C) 2016 by American Society of Clinical Oncology C1 [McCarthy, Anne Marie; Bristol, Mirar; Kim, Younji; Armstrong, Katrina] Massachusetts Gen Hosp, 50 Staniford St,9-940F, Boston, MA 02114 USA. [McCarthy, Anne Marie; Armstrong, Katrina] Harvard Med Sch, Boston, MA USA. [Domchek, Susan M.; Groeneveld, Peter W.; Motanya, U. Nkiru; Shea, Judy A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. RP McCarthy, AM (reprint author), Massachusetts Gen Hosp, 50 Staniford St,9-940F, Boston, MA 02114 USA. EM amccarthy8@partners.org FU National Cancer Institute, National Institutes of Health [5-R01-CA133004-3]; Florida Department of Health (FDOH) [BE0910]; Bureau of Health Statistics & Registries, Pennsylvania Department of Health [IF-0317] FX Supported by Grant No. 5-R01-CA133004-3 from the National Cancer Institute, National Institutes of Health.; The Florida cancer incidence data used in this report were collected by the Florida Cancer Data System (FCDS) under contract with the Florida Department of Health (FDOH) (Project N.: BE0910). The views expressed herein are solely those of the author(s) and do not necessarily reflect those of the FCDS or FDOH. The Bureau of Health Statistics & Registries, Pennsylvania Department of Health, has also provided data for this study (Project N.: IF-0317). The Pennsylvania Department of Health specifically disclaims responsibility for any analyses, interpretations, or conclusions. NR 66 TC 3 Z9 3 U1 7 U2 7 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 AUG 1 PY 2016 VL 34 IS 22 BP 2610 EP U96 DI 10.1200/JCO.2015.66.0019 PG 10 WC Oncology SC Oncology GA DU8LQ UT WOS:000382465300009 PM 27161971 ER PT J AU Eneanya, ND Winter, M Cabral, H Waite, K Henault, L Bickmore, T Hanchate, A Wolf, M Paasche-Orlow, MK AF Eneanya, Nwamaka D. Winter, Michael Cabral, Howard Waite, Katherine Henault, Lori Bickmore, Timothy Hanchate, Amresh Wolf, Michael Paasche-Orlow, Michael K. TI Health Literacy and Education as Mediators of Racial Disparities in Patient Activation Within an Elderly Patient Cohort SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Health literacy; education; patient activation; racial disparities ID RANDOMIZED CONTROLLED-TRIAL; OLDER-ADULTS; SELF-MANAGEMENT; SMOKING-CESSATION; MEASURE PAM; OUTCOMES; CARE; DEPRESSION; DISEASE; VALIDATION AB The Patient Activation Measure (PAM) assesses facets of patient engagement to identify proactive health behaviors and is an important predictor of health outcomes. Health literacy and education are also important for patient participation and successful navigation of the health care system. Because health literacy, education, and patient activation are associated with racial disparities, we sought to investigate whether health literacy and education would mediate racial differences in patient activation. Participants were 265 older adults who participated in a computer-based exercise interventional study. Health literacy was assessed using the Test of Functional Health Literacy in Adults (TOFHLA). Of 210 eligible participants, 72% self-identified as Black and 28% as White. In adjusted analyses, education and health literacy each significantly reduced racial differences in patient activation. These findings are especially important when considering emerging data on the significance of patient activation and new strategies to increase patient engagement. C1 [Eneanya, Nwamaka D.] Harvard Med Sch, Dept Internal Med, Massachusetts Gen Hosp, Div Nephrol, 165 Cambridge St,Suite 302, Boston, MA 02114 USA. [Winter, Michael; Cabral, Howard] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA USA. [Waite, Katherine; Henault, Lori; Hanchate, Amresh; Paasche-Orlow, Michael K.] Boston Univ, Sch Med, Dept Internal Med, Sect Gen Internal Med,Boston Med Ctr, Boston, MA 02118 USA. [Bickmore, Timothy; Wolf, Michael] Northeastern Univ, Coll Comp & Informat Sci, Boston, MA 02115 USA. RP Eneanya, ND (reprint author), Harvard Med Sch, Dept Internal Med, Massachusetts Gen Hosp, Div Nephrol, 165 Cambridge St,Suite 302, Boston, MA 02114 USA. EM Aeneanya@partners.org FU National Heart Lung and Blood Institute (NHLBI) FX Funding: This work was supported through a National Heart Lung and Blood Institute (NHLBI) Grant. NR 53 TC 0 Z9 0 U1 5 U2 5 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 EI 1548-6869 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD AUG PY 2016 VL 27 IS 3 BP 1427 EP 1440 PG 14 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DT2RV UT WOS:000381329000036 PM 27524777 ER PT J AU Zacharoulis, S La Madrid, AM Bandopadhayay, P Chi, SN Manley, P Ullrich, NNJ Marcus, K Goumnerova, L Scott, RM Proctor, M Young-Poussaint, T De Girolami, U Kieran, MW AF Zacharoulis, Stergios Morales La Madrid, Andres Bandopadhayay, Pratiti Chi, Susan N. Manley, Peter Ullrich, Nicole N. J. Marcus, Karen Goumnerova, Liliana Scott, Robert M. Proctor, Mark Young-Poussaint, Tina De Girolami, Umberto Kieran, Mark W. TI Central Versus Extraventricular Neurocytoma in Children: A Clinicopathologic Comparison and Review of the Literature SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE central neurocytomas; extraventricular neurocytomas; MIB-1; children; treatment ID GAMMA-KNIFE RADIOSURGERY; MIB-1 LABELING INDEX; MR-IMAGING FINDINGS; INTRAVENTRICULAR NEUROCYTOMA; INCOMPLETE RESECTION; CRANIOSPINAL DISSEMINATION; TYPICAL NEUROCYTOMAS; CEREBRAL NEUROCYTOMA; AVAILABLE TREATMENT; SPINAL-CORD AB Background:Central neurocytomas (CN) are rare pediatric CNS tumors most often with a benign clinical course. Occasionally, these tumors occur outside the ventricles and are called extraventricular neurocytomas (EVN). We present a retrospective institutional analysis of children with neurocytoma with prolonged follow-up.Procedure:Twelve patients were diagnosed with neurocytoma at our institution between 1993 and 2004.Results:Six patients were male and the median age at diagnosis was 12 years (1.5 to 16 y). Seven patients had CN and 5 had EVN. Presenting symptoms included headaches (67%), vomiting (50%), nausea (33%), seizures (33%), and mental status changes (25%). Obstructive hydrocephalus was present at diagnosis in 42% of the cases. Younger age and seizures were more common in patients with EVN. Gross total resection (GTR) was achieved in 42% (5/12) of the patients. Patients with GTR received no adjuvant therapy upfront; 1 patient subsequently had recurrence with leptomeningeal disease. Patients with subtotal resection received additional treatment: 1 underwent reoperation (GTR), 2 patients received focal radiation, 2 patients received adjuvant chemotherapy, and 2 patients received craniospinal irradiation followed by chemotherapy. The 20-year overall survival for this cohort was 83% with event free survival of 56%. Overall survival for CNs was 100%, versus 40% for EVN. Event free survival for CNs was 57% and 53% for the EVNs. An MIB-1 fraction >2% was associated with worse prognosis.Conclusions:Neurocytomas are rare brain tumors in children usually cured with GTR. Adjuvant focal radiation therapy and/or chemotherapy may improve disease control in cases with subtotal resection, but case-by-case analysis should be done. EVNs might be associated with worse outcome due to a higher proliferative index. C1 [Zacharoulis, Stergios] Royal Marsden NHS Fdn Trust, Children & Young Peoples Unit, Sutton, Surrey, England. [Morales La Madrid, Andres; Bandopadhayay, Pratiti; Chi, Susan N.; Manley, Peter; Ullrich, Nicole N. J.; Marcus, Karen; Goumnerova, Liliana; Kieran, Mark W.] Dana Farber Canc Inst, Pediat Neurooncol, Boston, MA 02115 USA. [Morales La Madrid, Andres; Bandopadhayay, Pratiti; Chi, Susan N.; Manley, Peter; Kieran, Mark W.] Boston Childrens Hosp, Dept Pediat Hematol Oncol, Boston, MA USA. [Ullrich, Nicole N. J.] Boston Childrens Hosp, Dept Neurol, Boston, MA USA. [Marcus, Karen] Boston Childrens Hosp, Dept Radiat Oncol, Boston, MA USA. [Goumnerova, Liliana; Scott, Robert M.; Proctor, Mark] Boston Childrens Hosp, Dept Neurosurg, Boston, MA USA. [Young-Poussaint, Tina] Boston Childrens Hosp, Dept Radiol, Boston, MA USA. [De Girolami, Umberto] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Morales La Madrid, Andres] Hosp St Joan de Deu, Dept Pediat Hematol & Oncol, Barcelona, Spain. RP Kieran, MW (reprint author), Dana Farber Canc Inst, Pediat Med Neurooncol, 450 Brookline Ave,Rm D-3154, Boston, MA 02215 USA. EM mark_kieran@dfci.harvard.edu FU Stop&Shop Pediatric Brain Tumor Program; St Baldrick's Foundation FX Supported in part by funding from the Stop&Shop Pediatric Brain Tumor Program (M.W.K.) and by the St Baldrick's Foundation (A.M.L.M.). NR 82 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1077-4114 EI 1536-3678 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD AUG PY 2016 VL 38 IS 6 BP 479 EP 485 DI 10.1097/MPH.0000000000000627 PG 7 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA DU9SP UT WOS:000382558300022 PM 27438020 ER PT J AU Ryu, WS Schellingerhout, D Jeong, SW Nahrendorf, M Kim, DE AF Ryu, Wi-Sun Schellingerhout, Dawid Jeong, Sang-Wook Nahrendorf, Matthias Kim, Dong-Eog TI Association between Serum Lipid Profiles and Early Neurological Deterioration in Acute Ischemic Stroke SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Cerebral infarct; lipids and lipoproteins; apolipoproteins; early neurological deterioration ID APOLIPOPROTEIN-A-I; METABOLIC SYNDROME; RISK; INFARCTION; ATHEROSCLEROSIS; HYPERGLYCEMIA; THROMBOLYSIS; MULTICENTER; PROGRESSION; PREDICTORS AB Background: Dyslipidemia is associated with chronic cardiovascular disease. However, the effect of dyslipidemia on acute ischemic stroke is unclear. We hypothesized that dyslipidemia could contribute to early neurological deterioration (END) after ischemic stroke. Methods: A total of 410 acute ischemic stroke patients who were admitted to our stroke center within 24 hours after ictus were consecutively included in this study. END was defined as any new neurological symptoms/signs or any neurological worsening occurring during the admission and/or within 3 weeks after the index stroke. Multivariable logistic regression was used to examine the independent association between lipid indices and END. Results: Mean age was 68.2 +/- 13.3 years, 241 (58.8%) were male, and 78 (19.0%) experienced END. Almost END occurred within 3 days after admission (n = 70, 89.7%), and the majority of END was stroke progression (n = 68, 87.1%). In univariate analysis, high-density lipoprotein (HDL)-cholesterol levels (per 1 mmol/L; odds ratio [OR] .37; 95% CI .17-.80; P = .012) and apolipoprotein B (apoB)/apoA-I ratio (per 1 increase; OR 3.71; 95% CI 1.48-9.29; P = .005) were associated with END. In the multivariable analysis, adjusted ORs of END for the highest quartile of HDL-cholesterol and apoB/apoA-I ratio were.42 (95% CI.19-. 94; P = .034) and 2.37 (95% CI 1.02-5.53; P = .045), respectively. The ratio of apoB/apoA-I was associated with END in large artery atherosclerosis stroke but not in other stroke subtypes. Conclusions: Independent association of low HDL-cholesterol and high apoB/apoA-I ratio with END warrants further research to investigate if correction of the lipid profile during the acute period of ischemic stroke could reduce the risk of END. C1 [Ryu, Wi-Sun; Jeong, Sang-Wook; Kim, Dong-Eog] Dongguk Univ, Ilsan Hosp, Stroke Ctr, Dept Neurol, Goyang, South Korea. [Ryu, Wi-Sun; Jeong, Sang-Wook; Kim, Dong-Eog] Dongguk Univ, Ilsan Hosp, Korean Brain MRI Data Ctr, Goyang, South Korea. [Schellingerhout, Dawid] Univ Texas MD Anderson Canc Ctr, Dept Radiol, Houston, TX USA. [Schellingerhout, Dawid] Univ Texas MD Anderson Canc Ctr, Dept Expt Diagnost Imaging, Houston, TX USA. [Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA USA. [Nahrendorf, Matthias] Harvard Med Sch, Boston, MA USA. RP Ryu, WS; Kim, DE (reprint author), Dongguk Univ, Ilsan Hosp, Dept Neurol, 814 Siksa Dong, Goyang Si, Gyeonggi Do, South Korea. EM wisunryu@gmail.com; kdongeog@duih.org FU Ministry of Health Welfare [HI12C1847, HI12C0066l]; National Research Foundation - Korean government, Republic of Korea [NRF-2015K1A1A2028228] FX This research was supported by grants of the Ministry of Health & Welfare (HI12C1847 and HI12C0066l; Korea Health Technology R&D Project) and the National Research Foundation (NRF-2015K1A1A2028228; Global Research Program), funded by the Korean government, Republic of Korea. NR 34 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 EI 1532-8511 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD AUG PY 2016 VL 25 IS 8 BP 2024 EP 2030 DI 10.1016/j.jstrokecerebrovasdis.2016.05.009 PG 7 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA DS7BO UT WOS:000380937700038 PM 27256172 ER PT J AU Scott, JC Woods, SP Wrocklage, KM Schweinsburg, BC Southwick, SM Krystal, JH AF Scott, J. Cobb Woods, Steven Paul Wrocklage, Kristen M. Schweinsburg, Brian C. Southwick, Steven M. Krystal, John H. TI Prospective Memory in Posttraumatic Stress Disorder SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Posttraumatic stress disorder; Neuropsychology; Cognitive abilities; Prospective memory; Memory; Anxiety ID INTENTIONS SCREENING-TEST; NEUROPSYCHOLOGICAL PERFORMANCE; NEUROCOGNITIVE DISORDERS; FUNCTIONAL OUTCOMES; COGNITIVE FUNCTION; LOCUS-COERULEUS; HIV-INFECTION; YOUNG-ADULTS; OLDER-ADULTS; PTSD AB Objectives: Neuropsychological studies of posttraumatic stress disorder (PTSD) have revealed deficits in attention/working memory, processing speed, executive functioning, and retrospective memory. However, little is known about prospective memory (PM) in PTSD, a clinically relevant aspect of episodic memory that supports the encoding and retrieval of intentions for future actions. Methods: Here we examined PM performance in 40 veterans with PTSD compared to 38 trauma comparison (TC) veterans who were exposed to combat but did not develop PTSD. All participants were administered the Memory for Intentions Test (MIST; Raskin, Buckheit, & Sherrod, 2010), a standardized and validated measure of PM, alongside a comprehensive neurocognitive battery, structured diagnostic interviews for psychiatric conditions, and behavioral questionnaires. Results: Veterans with PTSD performed moderately lower than TC on time-based PM, with errors primarily characterized as PM failure errors (i.e., omissions). However, groups did not differ in event-based PM, ongoing task performance, or post-test recognition of PM intentions for each trial. Lower time-based PM performance was specifically related to hyperarousal symptoms of PTSD. Time-based-performance was also associated with neuropsychological measures of retrospective memory and executive functions in the PTSD group. Nevertheless, PTSD was significantly associated with poorer PM above and beyond age and performance in retrospective memory and executive functions. Discussion: Results provide initial evidence of PM dysfunction in PTSD, especially in strategic monitoring during time-based PM tasks. Findings have potential implications for everyday functioning and health behaviors in persons with PTSD, and deserve replication and future study. C1 [Scott, J. Cobb] Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr VISN4, Philadelphia, PA USA. [Scott, J. Cobb] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Woods, Steven Paul] Univ Houston, Dept Psychol, Houston, TX USA. [Wrocklage, Kristen M.; Schweinsburg, Brian C.; Southwick, Steven M.; Krystal, John H.] Natl Ctr PTSD, Clin Neurosci Div, VA Connecticut Healthcare Syst, West Haven, CT USA. [Wrocklage, Kristen M.; Schweinsburg, Brian C.; Southwick, Steven M.; Krystal, John H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Krystal, John H.] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT USA. [Krystal, John H.] Yale New Haven Med Ctr, Psychiat Serv, 20 York St, New Haven, CT 06504 USA. RP Scott, JC (reprint author), Philadelphia VA Med Ctr, MIRECC 116, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM scott1@upenn.edu FU Department of Veterans Affairs Career Development Award [IK2CX000772]; National Center for PTSD (NCPTSD); National Center for Advancing Translational Science [1UH2TR000960-01]; Department of Veterans Affairs (NCPTSD); National Institute on Alcohol Abuse and Alcoholism [P50AA12870, M01RR00125]; Yale Center for Clinical Investigation [UL1 RR024139]; Neuroimaging Core for the VA/DOD Consortium; [R01MH073419]; [R01DA034497] FX This study is dedicated to the memory of Henry Krystal, M.D., pioneer of the impact of massive psychic trauma, who died on October 8, 2015. This work was supported by a Department of Veterans Affairs Career Development Award (IK2CX000772) to Dr. Scott, as well as the National Center for PTSD (NCPTSD). Dr. Krystal's participation was supported by the National Center for Advancing Translational Science (1UH2TR000960-01), the Department of Veterans Affairs (NCPTSD), the Neuroimaging Core for the VA/DOD Consortium to Alleviate PTSD, the National Institute on Alcohol Abuse and Alcoholism (P50AA12870, M01RR00125), and the Yale Center for Clinical Investigation (UL1 RR024139). Dr. Woods is supported by R01MH073419 and R01DA034497. 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. The authors declare no conflicts of interest. NR 77 TC 0 Z9 0 U1 15 U2 15 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 EI 1469-7661 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD AUG PY 2016 VL 22 IS 7 BP 724 EP 734 DI 10.1017/S1355617716000564 PG 11 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA DU8SQ UT WOS:000382485100004 PM 27353125 ER PT J AU Lemos, R Santana, I Caetano, G Bernardino, I Morais, R Farivar, R Castelo-Branco, M AF Lemos, Raquel Santana, Isabel Caetano, Gina Bernardino, Ines Morais, Ricardo Farivar, Reza Castelo-Branco, Miguel TI Three-Dimensional Face Recognition in Mild Cognitive Impairment: A Psychophysical and Structural MR Study SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Mild cognitive impairment; Cortical thickness; Vision; Fusiform; Dorsal pathway; Ventral pathway; Structure-from-motion ID HUMAN CEREBRAL-CORTEX; STRUCTURE-FROM-MOTION; EARLY ALZHEIMERS-DISEASE; SURFACE-BASED ANALYSIS; MAGNOCELLULAR IMPAIRMENT; HUMAN BRAIN; DORSAL; DEFICITS; FMRI; INTEGRATION AB Objectives: Mild cognitive impairment (MCI) has been associated with a high risk of conversion to Alzheimer's dementia. In addition to memory complaints, impairments in the visuospatial domain have been reported in this condition. We have previously shown that deficits in perceiving structure-from-motion (SFM) objects are reflected in functional reorganization of brain activity within the visual ventral stream. Here we aimed to identify structural correlates of psychophysical complex face and object recognition performance in amnestic MCI patients (n=30 vs. n=25 controls). This study was, therefore, motivated by evidence from recent studies showing that a combination of visual information across dorsal and ventral visual streams may be needed for the perception of three-dimensional (3D) SFM objects. Methods: In our experimental paradigm, participants had to discriminate 3D SFM shapes (faces and objects) from 3D SFM meaningless (scrambled) shapes. Results: Morphometric analysis established neuroanatomical evidence for impairment in MCI as demonstrated by smaller hippocampal volumes. We found association between cortical thickness and face recognition performance, comprising the occipital lobe and visual ventral stream fusiform regions (overlapping the known location of face fusiform area) in the right hemisphere, in MCI. Conclusions: We conclude that impairment of 3D visual integration exists at the MCI stage involving also the visual ventral stream and contributing to face recognition deficits. The specificity of such observed structure-function correlation for faces suggests a special role of this processing pathway in health and disease. C1 [Lemos, Raquel; Caetano, Gina; Bernardino, Ines; Castelo-Branco, Miguel] Univ Coimbra, Fac Med, Inst Biomed Imaging & Life Sci CNC IBILI, Visual Neurosci Lab,IBILI, Coimbra, Portugal. [Lemos, Raquel] Univ Coimbra, Fac Psychol & Educ Sci, Coimbra, Portugal. [Santana, Isabel] Ctr Hosp Univ Coimbra, Neurol Dept, Coimbra, Portugal. [Morais, Ricardo] Ctr Hosp Univ Coimbra, Neuroradiol Dept, Coimbra, Portugal. [Farivar, Reza] Harvard Med Sch, Charlestown, MA USA. [Farivar, Reza] Massachusetts Gen Hosp, A Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Farivar, Reza] McGill Univ, McGill Vis Res, Montreal, PQ, Canada. RP Castelo-Branco, M (reprint author), Univ Coimbra, IBILI Fac Med, Visual Neurosci Lab, P-3000354 Coimbra, Portugal. EM mcbranco@ibili.uc.pt RI Caetano, Gina/L-9340-2015; OI Caetano, Gina/0000-0001-6878-6079; Castelo-Branco, Miguel/0000-0003-4364-6373 FU Foundation for Science and Technology Portugal [SFRH/BD/74070/2010, PIC/IC/83206/2007, PTDC/SAU-ENB/112306/2009, CENTRO-07-ST24-FEDER-00205, FCT- UID/NEU/04539/2013]; COMPETE [POCI-01-0145-FEDER-007440] FX Authors thank all the participants. Authors also thank Carlos Ferreira and Joao Marques for help with MRI scanning, as well as Francisco Caramelo and Joao Pereira for help with statistical analysis. None of the authors have any conflict of interest related to this work. This work was supported by grants from the Foundation for Science and Technology Portugal: SFRH/BD/74070/2010 (to R.L.); PIC/IC/83206/2007 (to I.S.); Programa Ciencia 2008 and PTDC/SAU-ENB/112306/2009 (to G.C.); CENTRO-07-ST24-FEDER-00205, FCT- UID/NEU/04539/2013, and COMPETE, POCI-01-0145-FEDER-007440 (to M.C.B.). NR 66 TC 0 Z9 0 U1 2 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 EI 1469-7661 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD AUG PY 2016 VL 22 IS 7 BP 744 EP 754 DI 10.1017/S135561771600059X PG 11 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA DU8SQ UT WOS:000382485100006 PM 27406061 ER PT J AU Sangji, NF Bohnen, JD Ramly, EP Yeh, DD King, DR DeMoya, M Butler, K Fagenholz, PJ Velmahos, GC Chang, DC Kaafarani, HMA AF Sangji, Naveen F. Bohnen, Jordan D. Ramly, Elie P. Yeh, Daniel D. King, David R. DeMoya, Marc Butler, Kathryn Fagenholz, Peter J. Velmahos, George C. Chang, David C. Kaafarani, Haytham M. A. TI Derivation and validation of a novel Emergency Surgery Acuity Score (ESAS) SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Emergency surgery; mortality score; quality benchmarking; perioperative mortality; outcomes ID GENERAL-SURGERY; DISEASE; MORTALITY; OUTCOMES; PREDICTORS; SEVERITY; BURDEN; SYSTEM; SCALE; TOOL AB BACKGROUND: There currently exists no preoperative risk stratification system for emergency surgery (ES). We sought to develop an Emergency Surgery Acuity Score (ESAS) that helps predict perioperative mortality in ES patients. METHODS: Using the 2011 American College of Surgeons' National Surgical Quality Improvement Program (ACS-NSQIP) database (derivation cohort), we identified all surgical procedures that were classified as "emergent." A three-step methodology was then performed. First, multiple logistic regression models were created to identify independent predictors (e.g., patient demographics, comorbidities, and preoperative laboratory variables) of 30-day mortality in ES. Second, based on the relative impact of each identified predictor (i.e., odds ratio), using weighted averages, a novel score was derived. Third, using the 2012 ACS-NSQIP database (validation cohort), the score was validated by calculating its C statistic and evaluating its ability to predict 30-day mortality. RESULTS: From 280,801 NSQIP cases, 18,439 ES cases were analyzed, of which 1,598 (8.7%) resulted in death at 30 days. The multiple logistic regression analyses identified 22 independent predictors of mortality. Based on the relative impact of these predictors, ESAS was derived with a total score range of 0 to 29. ESAS had a C statistic of 0.86; the probability of death at 30 days gradually increased from 0% to 36% then 100% at scores of 0, 11, and 22, respectively. In the validation phase, 19,552 patients were included, the mortality rate was 7.2%, and the ESAS C statistic stayed at 0.86. CONCLUSION: We have therefore developed and validated a novel score, ESAS, that accurately predicts mortality in ES patients. Such a score could prove useful for (1) preoperative patient counseling, (2) identification of patients needing close postoperative monitoring, and (3) risk adjustment in any efforts at benchmarking the quality of ES. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved. C1 [Sangji, Naveen F.; Bohnen, Jordan D.; Ramly, Elie P.; Yeh, Daniel D.; King, David R.; DeMoya, Marc; Butler, Kathryn; Fagenholz, Peter J.; Velmahos, George C.; Kaafarani, Haytham M. A.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. [Sangji, Naveen F.; Chang, David C.; Kaafarani, Haytham M. A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Sangji, Naveen F.; Chang, David C.; Kaafarani, Haytham M. A.] Massachusetts Gen Hosp, Codman Ctr Clin Effectiveness Surg, Boston, MA 02114 USA. RP Kaafarani, HMA (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA.; Kaafarani, HMA (reprint author), Harvard Med Sch, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM Haytham.kaafarani@mgh.harvard.edu NR 28 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 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD AUG PY 2016 VL 81 IS 2 BP 213 EP 220 DI 10.1097/TA.0000000000001059 PG 8 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA DS5CE UT WOS:000380797300001 PM 27032007 ER PT J AU Gale, HI Bobbitt, CA Setty, BN Sprinz, PG Doros, G Williams, DD Morrison, TC Kalajian, TA Tu, P Mundluru, SN Castro-Aragon, I AF Gale, Heather I. Bobbitt, Christopher A. Setty, Bindu N. Sprinz, Philippa G. Doros, Gheorghe Williams, Don D. Morrison, Trevor C. Kalajian, Tyler A. Tu, Powen Mundluru, Shankar N. Castro-Aragon, Ilse TI Expected Sonographic Appearance of the Spleen in Children and Young Adults With Sickle Cell Disease An Update SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE pediatrics; pediatric ultrasound; sickle cell disease; sonography; spleen ID ANEMIA; LIVER; TRANSFUSIONS; HYDROXYUREA; THALASSEMIA; RELAXATION; ULTRASOUND; ASPLENIA; PATIENT; TISSUE AB Objectives-To update the imaging literature regarding spleen appearances in young patients with sickle cell disease (SCD). Methods-We conducted a retrospective study and included 112 patients age 0 to 21 years with SCD who had at least 1 abdominal sonogram at our institution between 1999 and 2011. Radiologic findings were compared between risk groups by chi(2) analysis. Findings were correlated with other imaging modalities when available. Results-In our cohort, 35.7% of patients had autosplenectomy, and 8.0% had undergone surgical splenectomy. Only 5.0% of individuals age 0 to 5 years had auto splenectomy. In those who had not undergone surgical splenectomy or autosplenectomy, 76.2% had echogenic spleens, heterogeneous-appearing spleens, or both, and patients with the homozygous sickle cell anemia (HbSS) genotype were more likely to have an abnormal spleen echo texture. Patients treated with transfusions had echogenic spleens and had a higher frequency of splenic regeneration nodules. Most patients (80%) with splenomegaly did not require surgical splenectomy after 5.7 years of follow-up. Conclusions-Twenty years ago, children with HbSS SCD were expected to have autosplenectomy by age 5 years. There have been changes in the radiologic appearance of the spleen in patients with SDC, likely due to improved supportive care and the use of acute and chronic transfusion therapy. We found that autosplenectomy is rare by age 5 years, and during childhood and adolescence, the spleen typically appears echogenic, heterogeneous, or both, depending on disease severity. C1 [Gale, Heather I.] Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. [Bobbitt, Christopher A.; Mundluru, Shankar N.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Setty, Bindu N.; Castro-Aragon, Ilse] Boston Univ, Boston Med Ctr, Boston, MA 02215 USA. [Sprinz, Philippa G.] Hasbro Childrens Hosp, Providence, RI USA. [Doros, Gheorghe] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Williams, Don D.] Univ Utah, Salt Lake City, UT USA. [Morrison, Trevor C.] Beth Israel Deaconess Med Ctr, Brookline, MA USA. [Kalajian, Tyler A.] Boston Univ, Sch Med, Dept Med Clin Sci, Grad Med Studies, Boston, MA 02118 USA. [Tu, Powen] Stanford Univ, Stanford, CA 94305 USA. RP Gale, HI (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. NR 30 TC 0 Z9 0 U1 2 U2 2 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 EI 1550-9613 J9 J ULTRAS MED JI J. Ultrasound Med. PD AUG 1 PY 2016 VL 35 IS 8 BP 1735 EP 1745 DI 10.7863/ultra.15.09023 PG 11 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA DU9HJ UT WOS:000382527000014 PM 27353067 ER PT J AU Nathavitharana, RR Peters, J Lederer, P von Delft, A Farley, JE Pai, M Jaramillo, E Raviglione, M Nardell, E AF Nathavitharana, Ruvandhi R. Peters, Jurgens Lederer, Philip von Delft, Arne Farley, Jason E. Pai, Madhukar Jaramillo, Ernesto Raviglione, Mario Nardell, Edward TI Engaging health-care workers to reduce tuberculosis transmission SO LANCET INFECTIOUS DISEASES LA English DT Editorial Material ID DRUG-RESISTANT TUBERCULOSIS; INFECTION C1 [Nathavitharana, Ruvandhi R.; Peters, Jurgens; Lederer, Philip; von Delft, Arne] TB Proof, Cape Town, South Africa. [Nathavitharana, Ruvandhi R.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. [Peters, Jurgens] London Sch Hyg & Trop Med, Fac Infect & Trop Dis, London, England. [Lederer, Philip] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [von Delft, Arne] Univ Cape Town, Fac Hlth Sci, Sch Publ Hlth & Family Med, Cape Town, South Africa. [Farley, Jason E.] Johns Hopkins Univ, Sch Nursing & Med, Baltimore, MD USA. [Pai, Madhukar] McGill Univ, Dept Epidemiol & Biostat, Montreal, PQ, Canada. [Jaramillo, Ernesto; Raviglione, Mario] WHO, Global TB Programme, Geneva, Switzerland. [Nardell, Edward] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. RP Nathavitharana, RR (reprint author), TB Proof, Cape Town, South Africa.; Nathavitharana, RR (reprint author), Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. EM rnathavi@bidmc.harvard.edu FU NIAID NIH HHS [T32 AI007061] NR 15 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 1473-3099 EI 1474-4457 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD AUG PY 2016 VL 16 IS 8 BP 883 EP 885 PG 4 WC Infectious Diseases SC Infectious Diseases GA DU4XH UT WOS:000382215700016 PM 27477968 ER PT J AU Anstead, GM AF Anstead, Gregory M. TI The centenary of the discovery of trench fever, an emerging infectious disease of World War 1 SO LANCET INFECTIOUS DISEASES LA English DT Review ID BARTONELLA-QUINTANA; RICKETTSIA QUINTANA; DISORDERED ACTION; RELAPSING FEVER; WAR; EPIDEMIC; ETIOLOGY; HENSELAE; ORIGIN; FORCES AB In 1915, a British medical officer on the Western Front reported on a soldier with relapsing fever, headache, dizziness, lumbago, and shin pain. Within months, additional cases were described, mostly in frontline troops, and the new disease was called trench fever. More than 1 million troops were infected with trench fever during World War 1, with each affected soldier unfit for duty for more than 60 days. Diagnosis was challenging, because there were no pathognomonic signs and symptoms and the causative organism could not be cultured. For 3 years, the transmission and cause of trench fever were hotly debated. In 1918, two commissions identified that the disease was louse-borne. The bacterium Rickettsia quintana was consistently found in the gut and faeces of lice that had fed on patients with trench fever and its causative role was accepted in the 1920s. The organism was cultured in the 1960s and reclassified as Bartonella quintana; it was also found to cause endocarditis, peliosis hepatis, and bacillary angiomatosis. Subsequently, B quintana infection has been identified in new populations in the Andes, in homeless people in urban areas, and in individuals with HIV. The story of trench fever shows how war can lead to the recrudescence of an infectious disease and how medicine approached an emerging infection a century ago. C1 [Anstead, Gregory M.] South Texas Vet Hlth Care Syst, Med Serv, San Antonio, TX USA. [Anstead, Gregory M.] Univ Texas Hlth Sci Ctr San Antonio, Div Infect Dis, Dept Med, San Antonio, TX 78229 USA. RP Anstead, GM (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Infect Dis, Dept Med, San Antonio, TX 78229 USA. EM anstead@uthscsa.edu NR 81 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 1473-3099 EI 1474-4457 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD AUG PY 2016 VL 16 IS 8 BP E164 EP E172 DI 10.1016/S1473-3099(16)30003-2 PG 9 WC Infectious Diseases SC Infectious Diseases GA DU4XH UT WOS:000382215700003 PM 27375211 ER PT J AU Zimmaro, LA Salmon, P Naidu, H Rowe, J Phillips, K Rebholz, WN Giese-Davis, J Cash, E Dreeben, SJ Bayley-Veloso, R Jablonski, ME Hicks, A Siwik, C Sephton, SE AF Zimmaro, Lauren A. Salmon, Paul Naidu, Hemali Rowe, Jonathan Phillips, Kala Rebholz, Whitney N. Giese-Davis, Janine Cash, Elizabeth Dreeben, Samuel J. Bayley-Veloso, Rene Jablonski, Megan E. Hicks, Allison Siwik, Chelsea Sephton, Sandra E. TI Association of Dispositional Mindfulness with Stress, Cortisol, and Well-Being Among University Undergraduate Students SO MINDFULNESS LA English DT Article DE Mindfulness; Stress; Cortisol; Well-being; Undergraduate ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; COLLEGE-STUDENTS; FUNCTIONAL CONNECTIVITY; ADRENOCORTICAL ACTIVITY; PSYCHOLOGICAL STRESS; LONG-TERM; MEDITATION; REDUCTION; HEALTH AB Mindfulness has been associated with better psychological and physical health; although, the mechanisms of these benefits are poorly understood. We explored the role of mindfulness in stress-health pathways among undergraduates at a large public university. Participants reported on demographic and academic variables and completed data collection at two time points during the academic semester, approximately one month apart. At each collection, measures of mindfulness, perceived stress, and psychological well-being were gathered. Students provided two days of home-based saliva collection for assessment of cortisol. Mean scores were computed for each of the measures, over the two assessments. Hierarchical multiple regressions adjusting for GPA, hours of paid employment per week, minority status, and living situation explored the impact of mindfulness in our stress-health model. Students with higher dispositional mindfulness reported significantly less perceived stress and had lower overall mean diurnal cortisol. Mindfulness was associated with greater psychological well-being. Exploratory analyses suggested that future research should explore the potential mediating or moderating relationships between mindfulness, perceived stress, and cortisol. Findings suggest that mindfulness may help attenuate both psychological and physiological stress responses to college stress. C1 [Zimmaro, Lauren A.; Salmon, Paul; Naidu, Hemali; Rowe, Jonathan; Phillips, Kala; Rebholz, Whitney N.; Cash, Elizabeth; Bayley-Veloso, Rene; Jablonski, Megan E.; Hicks, Allison; Siwik, Chelsea; Sephton, Sandra E.] Univ Louisville, Dept Psychol & Brain Sci, Louisville, KY 40292 USA. [Giese-Davis, Janine] Univ Calgary, Dept Oncol, Div Psychosocial Oncol, Calgary, AB, Canada. [Cash, Elizabeth] Univ Louisville, Sch Med, Dept Otolaryngol Head & Neck Surg & Communicat Di, Louisville, KY 40292 USA. [Dreeben, Samuel J.] South Texas Vet Hlth Care Syst, Psychol Serv, San Antonio, TX USA. [Sephton, Sandra E.] Univ Louisville, James Graham Brown Canc Ctr, Louisville, KY 40292 USA. RP Sephton, SE (reprint author), Univ Louisville, Dept Psychol & Brain Sci, Louisville, KY 40292 USA.; Sephton, SE (reprint author), Univ Louisville, James Graham Brown Canc Ctr, Louisville, KY 40292 USA. EM psalmon@louisville.edu; sephton@louisville.edu FU Office of the Vice President for Research at the University of Louisville FX This study was funded through an undergraduate research grant from the Office of the Vice President for Research at the University of Louisville, awarded to Paul Salmon, Ph.D. NR 70 TC 0 Z9 0 U1 22 U2 27 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1868-8527 EI 1868-8535 J9 MINDFULNESS JI Mindfulness PD AUG PY 2016 VL 7 IS 4 BP 874 EP 885 DI 10.1007/s12671-016-0526-8 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DV3XX UT WOS:000382860000009 ER PT J AU Felleman, BI Stewart, DG Simpson, TL Heppner, PS Kearney, DJ AF Felleman, Benjamin I. Stewart, David G. Simpson, Tracy L. Heppner, Pia S. Kearney, David J. TI Predictors of Depression and PTSD Treatment Response Among Veterans Participating in Mindfulness-Based Stress Reduction SO MINDFULNESS LA English DT Article DE Mindfulness; PTSD; Depression; Treatment ID COGNITIVE-BEHAVIORAL THERAPY; INTIMATE PARTNER VIOLENCE; POSTTRAUMATIC-STRESS; PROCESSING THERAPY; ANXIETY DISORDERS; MAJOR DEPRESSION; MODERATORS; PROGRAM; INTERVENTION; REPLICATION AB Posttraumatic stress disorder (PTSD) and depression are prevalent and often co-occur among veterans. There is growing interest in the effects of mindfulness-based interventions among veterans. This study examined PTSD and depression outcomes, and baseline predictors of response, among veterans who participated in mindfulness-based stress reduction (MBSR). Participants included 116 veterans with PTSD before and after MBSR. Multilevel modeling assessed baseline predictors of change in PTSD and depressive symptoms. There were clinically significant reductions in PTSD and depression symptoms posttreatment and at 4 months follow-up. For PTSD, effect sizes were in the medium range posttreatment (d = -.63) and at follow-up (d = -.69), and for depression posttreatment (d = -.58) and at follow-up (d = -.70). Baseline PTSD was a significant predictor of slope (beta = .03, p = .04) on PTSD outcomes; higher baseline PTSD predicted greater rate of reduction in symptoms. For depression (beta = .04, p < .01,), those with severe or moderately severe depression exhibited the greatest rate of improvement. However, veterans with high symptom severity did remain symptomatic post-MBSR. These findings show preliminary support for MBSR in facilitating symptom reduction for veterans with severe PTSD and co-occurring depression. C1 [Felleman, Benjamin I.; Stewart, David G.] Seattle Pacific Univ, Dept Psychol Family & Community, 3307 Third Ave W Ste 107, Seattle, WA 98119 USA. [Felleman, Benjamin I.; Heppner, Pia S.] VA San Diego Hlth Care Syst, 3350 La Jolla Village Dr,116B, San Diego, CA 92161 USA. [Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ CESAT, 1660 South Columbian Way, Seattle, WA USA. [Simpson, Tracy L.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, 1959 NE Pacific St, Seattle, WA 98195 USA. [Heppner, Pia S.] Univ Calif San Diego, Dept Psychiat, Gilman Dr,MC 0603, San Diego, CA USA. [Kearney, David J.] VA Puget Sound Hlth Care Syst, 1660 South Columbian Way, Seattle, WA USA. [Kearney, David J.] Univ Washington, Sch Med, Dept Med, 1959 NE Pacific St, Seattle, WA 98195 USA. RP Felleman, BI (reprint author), Seattle Pacific Univ, Dept Psychol Family & Community, 3307 Third Ave W Ste 107, Seattle, WA 98119 USA.; Felleman, BI (reprint author), VA San Diego Hlth Care Syst, 3350 La Jolla Village Dr,116B, San Diego, CA 92161 USA. EM benjamin.felleman@va.gov NR 54 TC 0 Z9 0 U1 14 U2 14 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1868-8527 EI 1868-8535 J9 MINDFULNESS JI Mindfulness PD AUG PY 2016 VL 7 IS 4 BP 886 EP 895 DI 10.1007/s12671-016-0527-7 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DV3XX UT WOS:000382860000010 ER PT J AU Scapin, G Bertalot, T Vicentini, N Gatti, T Tescari, S De Filippis, V Marega, C Menna, E Gasparella, M Parnigotto, PP Di Liddo, R Filippini, F AF Scapin, Giorgia Bertalot, Thomas Vicentini, Nicola Gatti, Teresa Tescari, Simone De Filippis, Vincenzo Marega, Carla Menna, Enzo Gasparella, Marco Parnigotto, Pier Paolo Di Liddo, Rosa Filippini, Francesco TI Neuronal commitment of human circulating multipotent cells by carbon nanotube-polymer scaffolds and biomimetic peptides SO NANOMEDICINE LA English DT Article DE biomimetic peptides; carbon nanotubes; human circulating multipotent cells; nanocomposite scaffold; neuronal differentiation; regenerative medicine ID MESENCHYMAL STEM-CELLS; RETINOIC ACID; STROMAL CELLS; PRIMARY CULTURES; NERVOUS-SYSTEM; DIFFERENTIATION; TISSUE; BLOOD; EXPRESSION; MONOCYTES AB Aim: We aimed to set up a self-standing, biomimetic scaffold system able to induce and support per se neuronal differentiation of autologous multipotent cells. Materials & methods: We isolated a population of human circulating multipotent cells (hCMCs), and used carbon nanotube/polymer nanocomposite scaffolds to mimic electrical/nanotopographical features of the neural environment, and biomimetic peptides reproducing axon guidance cues from neural proteins. Results: hCMCs showed high degree of stemness and multidifferentiative potential; stimuli from the scaffolds and biomimetic peptides could induce and boost hCMC differentiation toward neuronal lineage despite the absence of exogenously added, specific growth factors. Conclusion: This work suggests the scaffold-peptides system combined with autologous hCMCs as a functional biomimetic, self-standing prototype for neural regenerative medicine applications. C1 [Scapin, Giorgia; Filippini, Francesco] Univ Padua, Dept Biol, I-35131 Padua, Italy. [Bertalot, Thomas; Tescari, Simone; De Filippis, Vincenzo; Di Liddo, Rosa] Univ Padua, Dept Pharmaceut & Pharmacol Sci, I-35131 Padua, Italy. [Vicentini, Nicola; Gatti, Teresa; Marega, Carla; Menna, Enzo] Univ Padua, Dept Chem Sci, I-35131 Padua, Italy. [Gasparella, Marco] Univ Padua, Dept Woman & Child Hlth, I-35128 Padua, Italy. [Parnigotto, Pier Paolo] Caselle Selvazzano Dentro, Tissue Engn & Signaling ONLUS, I-35030 Padua, Italy. [Scapin, Giorgia] Harvard Med Sch, Sect Islet Cell & Regenerat Biol, Joslin Diabet Ctr, Boston, MA 02215 USA. [Scapin, Giorgia] Harvard Med Sch, Dept Med, Boston, MA 02215 USA. RP Filippini, F (reprint author), Univ Padua, Dept Biol, I-35131 Padua, Italy.; Di Liddo, R (reprint author), Univ Padua, Dept Pharmaceut & Pharmacol Sci, I-35131 Padua, Italy. EM rosa.diliddo@unipd.it; francesco.filippini@unipd.it OI Gatti, Teresa/0000-0001-5343-8055 FU CaRiPaRo Foundation (Excellence Research Project); Italian Ministry of Education, Universities and Research - MIUR [PRIN-20104XET32]; University of Padova, Italy [PRAT2015 CPDA151948]; [CPDR137224/13] FX The authors acknowledge the financial support from CaRiPaRo Foundation (Excellence Research Project 2011 to V De Filippis), the Italian Ministry of Education, Universities and Research - MIUR (contract PRIN-20104XET32 to E Menna) and the University of Padova, Italy (basic "EX 60%" grants to R Di Liddo and F Filippini, Project PRAT2015 CPDA151948 to F Filippini). Research fellowship CPDR137224/13 to R Di Liddo (supporting T Bertalot) and PhD fellowship to G Scapin are gratefully acknowledged. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 59 TC 1 Z9 1 U1 4 U2 4 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 EI 1748-6963 J9 NANOMEDICINE-UK JI Nanomedicine PD AUG PY 2016 VL 11 IS 15 BP 1929 EP 1946 DI 10.2217/nnm-2016-0150 PG 18 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA DS9NL UT WOS:000381109900002 PM 27246559 ER PT J AU Ghaoui, R Benavides, T Lek, M Waddell, LB Kaur, S North, KN MacArthur, DG Clarke, NF Cooper, ST AF Ghaoui, Roula Benavides, Tatiana Lek, Monkol Waddell, Leigh B. Kaur, Simranpreet North, Kathryn N. MacArthur, Daniel G. Clarke, Nigel F. Cooper, Sandra T. TI TOR1AIP1 as a cause of cardiac failure and recessive limb-girdle muscular dystrophy SO NEUROMUSCULAR DISORDERS LA English DT Article DE Genetics; Muscular dystrophy; Limb-girdle; Cardiac failure; Cardiac transplant ID LAMIN A/C GENE; MUTATIONS; INTERACTS; SKELETAL; MYOPATHY; PROTEIN AB TorsinA-interacting protein 1 (TOR1AIP1) gene is a novel gene that has recently been described to cause limb-girdle muscular dystrophy (LGMD) with mild dilated cardiomyopathy. We report a family with mutations in TOR1AIP1 where the striking clinical feature is severe cardiac failure requiring cardiac transplant in two siblings, in addition to musculoskeletal weakness and muscular dystrophy. We demonstrate an absence of TOR1AIP1 protein expression in cardiac and skeletal muscles of affected siblings. We expand the phenotype of this gene to demonstrate the cardiac involvement and the importance of cardiac surveillance in patients with mutations in TOR1AIPI. (C) 2016 Elsevier B.V. All rights reserved. C1 [Ghaoui, Roula; Benavides, Tatiana; Waddell, Leigh B.; Kaur, Simranpreet; Clarke, Nigel F.; Cooper, Sandra T.] Childrens Hosp Westmead, Kids Res Inst, Inst Neurosci & Muscle Res, Sydney, NSW 2145, Australia. [Ghaoui, Roula; Clarke, Nigel F.; Cooper, Sandra T.] Univ Sydney, Sydney Med Sch, Discipline Paediat & Child Hlth, Sydney, NSW 2006, Australia. [Lek, Monkol; MacArthur, Daniel G.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Lek, Monkol; MacArthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [North, Kathryn N.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Melbourne, Vic 3052, Australia. RP Ghaoui, R; Cooper, ST (reprint author), Childrens Hosp Westmead, INMR, Westmead, NSW 2145, Australia. EM roula.ghaoui@health.nsw.gov.au; Sandra.cooper@sydney.edu.au RI North, Kathryn/K-6476-2012 OI North, Kathryn/0000-0003-0841-8009 FU National Health and Medical Research Council of Australia [1022707, 1031893, 1080587, 1035828, 1048816]; National Human Genome Research Institute of the US National Institutes of Health (Medical Sequencing Program) [U54 HG003067]; Novartis Foundation for Medical-Biological Research FX This work was funded by the National Health and Medical Research Council of Australia grants 1022707 and 1031893 (both NFC and KNN), 1080587 to DGM, KNN, NFC and STC, 1035828 (NFC) and 1048816 to STC. Exome sequencing was supported by grants from the National Human Genome Research Institute of the US National Institutes of Health (Medical Sequencing Program grant U54 HG003067 to the Broad Institute principal investigator, Lander). TBD was supported by the Novartis Foundation for Medical-Biological Research. NR 13 TC 2 Z9 2 U1 3 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 EI 1873-2364 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD AUG PY 2016 VL 26 IS 8 BP 500 EP 503 DI 10.1016/j.nmd.2016.05.013 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DT5TK UT WOS:000381545300004 PM 27342937 ER PT J AU Struck, AF Carr, CM Shah, V Hesselink, JR Haughton, VM AF Struck, Aaron F. Carr, Carrie M. Shah, Vinil Hesselink, John R. Haughton, Victor M. TI Cervical spinal canal narrowing in idiopathic syringomyelia SO NEURORADIOLOGY LA English DT Article DE Idiopathic syringomyelia; Cerebrospinal fluid; Cervical spinal canal; CSF flow dynamics ID CHIARI I MALFORMATION AB The cervical spine in Chiari I patient with syringomyelia has significantly different anteroposterior diameters than it does in Chiari I patients without syringomyelia. We tested the hypothesis that patients with idiopathic syringomyelia (IS) also have abnormal cervical spinal canal diameters. The finding in both groups may relate to the pathogenesis of syringomyelia. Local institutional review boards approved this retrospective study. Patients with IS were compared to age-matched controls with normal sagittal spine MR. All subjects had T1-weighted spin-echo (500/20) and T2-weighted fast spin-echo (2000/90) sagittal cervical spine images at 1.5 T. Readers blinded to demographic data and study hypothesis measured anteroposterior diameters at each cervical level. The spinal canal diameters were compared with a Mann-Whitney U test. The overall difference was assessed with a Friedman test. Seventeen subjects were read by two reviewers to assess inter-rater reliability. Fifty IS patients with 50 age-matched controls were studied. IS subjects had one or more syrinxes varying from 1 to 19 spinal segments. Spinal canal diameters narrowed from C1 to C3 and then enlarged from C5 to C7 in both groups. Diameters from C2 to C4 were narrower in the IS group (p < 0.005) than in controls. The ratio of the C3 to the C7 diameters was also smaller (p = 0.004) in IS than controls. Collectively, the spinal canal diameters in the IS were significantly different from controls (Friedman test p < 0.0001). Patients with IS have abnormally narrow upper and mid cervical spinal canal diameters and greater positive tapering between C3 and C7. C1 [Struck, Aaron F.] Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St Wang 735, Boston, MA 02114 USA. [Carr, Carrie M.] Mayo Clin, Dept Radiol, Rochester, MN USA. [Shah, Vinil] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA. [Hesselink, John R.] Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA. [Haughton, Victor M.] Univ Wisconsin, Dept Radiol, Madison, WI 53706 USA. RP Struck, AF (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St Wang 735, Boston, MA 02114 USA. EM astruck@mgh.harvard.edu NR 14 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0028-3940 EI 1432-1920 J9 NEURORADIOLOGY JI Neuroradiology PD AUG PY 2016 VL 58 IS 8 BP 771 EP 775 DI 10.1007/s00234-016-1701-2 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA DV2NN UT WOS:000382757400004 PM 27194170 ER PT J AU Nathwani, N Krishnan, AY Richardson, PG AF Nathwani, Nitya Krishnan, Amrita Y. Richardson, Paul G. TI Routine Use of Autologous Stem Cell Transplantation in Multiple Myeloma SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID LENALIDOMIDE; MULTICENTER; MAINTENANCE; THERAPY C1 [Nathwani, Nitya; Krishnan, Amrita Y.] City Hope Canc Ctr, Judy & Bernard Briskin Ctr Myeloma, Duarte, CA 91010 USA. [Richardson, Paul G.] Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Nathwani, N (reprint author), City Hope Canc Ctr, Judy & Bernard Briskin Ctr Myeloma, Duarte, CA 91010 USA. NR 14 TC 0 Z9 0 U1 2 U2 2 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 AUG PY 2016 VL 30 IS 8 BP 747 EP 749 PG 3 WC Oncology SC Oncology GA DT4LN UT WOS:000381452700010 ER PT J AU Scrivani, SJ AF Scrivani, Steven J. TI Oral and Maxillofacial Pain Preface SO ORAL AND MAXILLOFACIAL SURGERY CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 [Scrivani, Steven J.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Div Oral & Maxillofacial Pain, Warren 1201 55 Fruit St, Boston, MA 02114 USA. RP Scrivani, SJ (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Div Oral & Maxillofacial Pain, Warren 1201 55 Fruit St, Boston, MA 02114 USA. EM sscrivani1@partners.org NR 0 TC 0 Z9 0 U1 2 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1042-3699 EI 1558-1365 J9 ORAL MAXIL SURG CLIN JI Oral Maxillofac. Surg. Clin. N. Am. PD AUG PY 2016 VL 28 IS 3 BP XIII EP XIII DI 10.1016/j.coms.2016.06.013 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DU1FN UT WOS:000381953700001 PM 27475517 ER PT J AU Scrivani, SJ Spierings, ELH AF Scrivani, Steven J. Spierings, Egilius L. H. TI Classification and Differential Diagnosis of Oral and Maxillofacial Pain SO ORAL AND MAXILLOFACIAL SURGERY CLINICS OF NORTH AMERICA LA English DT Article DE Orofacial pain; Maxillofacial pain; Craniofacial pain; Classification; Differential diagnosis; Diagnostic evaluation; Physical examination; Diagnostic imaging ID TEMPOROMANDIBULAR DISORDERS; NOCICEPTIVE NEURONS; DORSAL-HORN; PROJECTIONS; COMPLEX; CORTEX; AREAS; RATS AB Pain in the orofacial region is a common presenting symptom. The majority of symptoms are related to dental disease, and the cause can readily be established, the problem dealt with, and the pain eliminated. However, pain may persist and defy attempts at treatment. Intractable oral or facial pain can be diagnostically challenging. To make a definitive diagnosis and initiate proper treatment, a rigorous protocol for evaluation includes a thorough history and an appropriate comprehensive clinical examination and diagnostic testing, including chief complaint, history of present illness, medical history, physical examination, diagnostic studies, including imaging, and psychosocial evaluation. C1 [Scrivani, Steven J.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Div Oral & Maxillofacial Pain, Warren 1201,15 Parkman St,Suite 230, Boston, MA 02114 USA. [Spierings, Egilius L. H.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Spierings, Egilius L. H.] Tufts Univ, Sch Dent Med, Boston, MA 02111 USA. RP Scrivani, SJ (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Div Oral & Maxillofacial Pain, Warren 1201,15 Parkman St,Suite 230, Boston, MA 02114 USA. EM sscrivani1@partners.org NR 15 TC 0 Z9 0 U1 3 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1042-3699 EI 1558-1365 J9 ORAL MAXIL SURG CLIN JI Oral Maxillofac. Surg. Clin. N. Am. PD AUG PY 2016 VL 28 IS 3 BP 233 EP + DI 10.1016/j.coms.2016.04.003 PG 15 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DU1FN UT WOS:000381953700002 PM 27475504 ER PT J AU Kulich, RJ Backstrom, J Brownstein, J Finkelman, M Dhadwal, S DiBennedetto, D AF Kulich, Ronald J. Backstrom, Jordan Brownstein, Jennifer Finkelman, Matthew Dhadwal, Shuchi DiBennedetto, David TI A Model for Opioid Risk Stratification Assessing the Psychosocial Components of Orofacial Pain SO ORAL AND MAXILLOFACIAL SURGERY CLINICS OF NORTH AMERICA LA English DT Article DE Opioid; Risk-management; Dentistry; Substance abuse; Interprofessional ID NEONATAL ABSTINENCE SYNDROME; MISUSE MEASURE; SOAPP-R; CROSS-VALIDATION; UNITED-STATES; SCREENER; ABUSE; REDUCTION; THERAPY; ANXIETY AB This article describes a model of opiate risk stratification with a special focus on dentistry and oral surgery. A brief overview covers the scope of the US opioid abuse and misuse epidemic and the role of the dentist in mitigating the problems of diversion and misuse of controlled substances. The expanding role of dentistry is summarized. An assessment outlines gathering critical risk information, screening questionnaires, access to state prescription monitoring programs, and communication with cotreating providers. Special populations are discussed. Barriers and possible solutions for effective implementation of these strategies are summarized. C1 [Kulich, Ronald J.; Brownstein, Jennifer; Dhadwal, Shuchi] Tufts Sch Dent Med, Craniofacial Pain & Headache Ctr, Dept Diagnost Sci, Boston, MA USA. [Kulich, Ronald J.; Brownstein, Jennifer] Massachusetts Gen Hosp, Harvard Med Sch, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Backstrom, Jordan] Boston Pain Care Ctr, Waltham, MA USA. [Finkelman, Matthew] Tufts Univ, Sch Dent Med, Dept Biostat & Expt Design, 1 Kneeland St,7th Floor, Boston, MA 02129 USA. [DiBennedetto, David] Boston Pain Care, Tufts Sch Dent Med, Dept Diagnost Sci, Boston, MA USA. [Kulich, Ronald J.; Brownstein, Jennifer] 15 Parkman St, Boston, MA 02114 USA. [Backstrom, Jordan; DiBennedetto, David] 85 First Ave, Waltham, MA 02451 USA. [Dhadwal, Shuchi] 1 Kneeland St,,6th Floor,7th Floor, Boston, MA 02129 USA. RP Kulich, RJ; Brownstein, J; Finkelman, M; Dhadwal, S (reprint author), 1 Kneeland St,,6th Floor,7th Floor, Boston, MA 02129 USA. EM rkulich@mgh.harvard.edu NR 53 TC 0 Z9 0 U1 3 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1042-3699 EI 1558-1365 J9 ORAL MAXIL SURG CLIN JI Oral Maxillofac. Surg. Clin. N. Am. PD AUG PY 2016 VL 28 IS 3 BP 261 EP + DI 10.1016/j.coms.2016.03.006 PG 14 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DU1FN UT WOS:000381953700004 PM 27475506 ER PT J AU Bajwa, ZH Smith, SS Khawaja, SN Scrivani, SJ AF Bajwa, Zahid H. Smith, Sarah S. Khawaja, Shehryar N. Scrivani, Steven J. TI Cranial Neuralgias SO ORAL AND MAXILLOFACIAL SURGERY CLINICS OF NORTH AMERICA LA English DT Article DE Cranial neuralgias; Trigeminal neuralgia; Compression ID IDIOPATHIC TRIGEMINAL NEURALGIA; MICROVASCULAR DECOMPRESSION SURGERY; GAMMA-KNIFE RADIOSURGERY; MULTIPLE-SCLEROSIS; HERPES-ZOSTER; NEUROPATHIC PAIN; FACIAL-PAIN; POSTERIOR-FOSSA; INTERNATIONAL CLASSIFICATION; GLOSSOPHARYNGEAL NEURALGIA AB Advances in diagnostic modalities have improved the understanding of the pathophysiology of neuropathic pain involving head and face. Recent updates in nomenclature of cranial neuralgias and facial pain have rationalized accurate diagnosis. Clear diagnosis and localization of pain generators are paramount, leading to better use of medical and targeted surgical treatments. C1 [Bajwa, Zahid H.] Tufts Univ, Sch Med, Boston Headache Inst, Boston Pain Care,Clin Res, Waltham, MA 02155 USA. [Smith, Sarah S.] Boston Headache Inst, Boston Pain Care, Waltham, MA USA. [Khawaja, Shehryar N.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Orofacial Pain Training Program, Boston, MA 02114 USA. [Scrivani, Steven J.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Div Oral & Maxillofacial Pain, Orofacial Pain Residency Training Program, Boston, MA 02114 USA. RP Bajwa, ZH (reprint author), Tufts Univ, Sch Med, Boston Headache Inst, Boston Pain Care,Clin Res, Waltham, MA 02155 USA. EM zbajwa@bostonpaincare.com NR 146 TC 1 Z9 1 U1 3 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1042-3699 EI 1558-1365 J9 ORAL MAXIL SURG CLIN JI Oral Maxillofac. Surg. Clin. N. Am. PD AUG PY 2016 VL 28 IS 3 BP 351 EP + DI 10.1016/j.coms.2016.04.001 PG 22 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DU1FN UT WOS:000381953700009 PM 27475511 ER PT J AU Goldstein, RD AF Goldstein, Richard D. TI RE: Overall Postneonatal Mortality and Rates of SIDS Response SO PEDIATRICS LA English DT Letter ID DEATH C1 [Goldstein, Richard D.] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA. RP Goldstein, RD (reprint author), Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA. EM richard_goldstein@dfci.harvard.edu NR 3 TC 0 Z9 0 U1 3 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD AUG PY 2016 VL 138 IS 2 DI 10.1542/peds.2016-1592C PG 1 WC Pediatrics SC Pediatrics GA DS7ZP UT WOS:000381002500066 ER PT J AU Heyne, TF AF Heyne, Thomas F. TI Lanfranco's Dropsical Child: The First Depiction of Congenital Heart Disease? SO PEDIATRICS LA English DT Article ID ART C1 [Heyne, Thomas F.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. [Heyne, Thomas F.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pediat, Boston, MA USA. RP Heyne, TF (reprint author), Harvard Internal Med & Pediat Residency, 175 Cambridge St,5th Fl, Boston, MA 02114 USA. EM theyne@partners.org NR 17 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD AUG PY 2016 VL 138 IS 2 AR e20154594 DI 10.1542/peds.2015-4594 PG 4 WC Pediatrics SC Pediatrics GA DS7ZP UT WOS:000381002500026 ER PT J AU Hoyme, HE Kalberg, WO Elliott, AJ Blankenship, J Buckley, D Marais, AS Manning, MA Robinson, LK Adam, MP Abdul-Rahman, O Jewett, T Coles, CD Chambers, C Jones, KL Adnams, CM Shah, PE Riley, EP Charness, ME Warren, KR May, PA AF Hoyme, H. Eugene Kalberg, Wendy O. Elliott, Amy J. Blankenship, Jason Buckley, David Marais, Anna-Susan Manning, Melanie A. Robinson, Luther K. Adam, Margaret P. Abdul-Rahman, Omar Jewett, Tamison Coles, Claire D. Chambers, Christina Jones, Kenneth L. Adnams, Colleen M. Shah, Prachi E. Riley, Edward P. Charness, Michael E. Warren, Kenneth R. May, Philip A. TI Updated Clinical Guidelines for Diagnosing Fetal Alcohol Spectrum Disorders SO PEDIATRICS LA English DT Article ID MATERNAL RISK-FACTORS; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PALPEBRAL FISSURE LENGTH; PREGNANCY RECOGNITION; HEAD CIRCUMFERENCE; BIRTH-DEFECTS; NEUROBEHAVIORAL PROFILE; FULL SPECTRUM; BRAIN VOLUME; SOUTH-AFRICA AB The adverse effects of prenatal alcohol exposure constitute a continuum of disabilities (fetal alcohol spectrum disorders [FASD]). In 1996, the Institute of Medicine established diagnostic categories delineating the spectrum but not specifying clinical criteria by which diagnoses could be assigned. In 2005, the authors published practical guidelines operationalizing the Institute of Medicine categories, allowing for standardization of FASD diagnoses in clinical settings. The purpose of the current report is to present updated diagnostic guidelines based on a thorough review of the literature and the authors' combined expertise based on the evaluation of >10 000 children for potential FASD in clinical settings and in epidemiologic studies in conjunction with National Institute on Alcohol Abuse and Alcoholism-funded studies, the Collaborative Initiative on Fetal Alcohol Spectrum Disorders, and the Collaboration on FASD Prevalence. The guidelines were formulated through conference calls and meetings held at National Institute on Alcohol Abuse and Alcoholism offices in Rockville, MD. Specific areas addressed include the following: precise definition of documented prenatal alcohol exposure; neurobehavioral criteria for diagnosis of fetal alcohol syndrome, partial fetal alcohol syndrome, and alcohol-related neurodevelopmental disorder; revised diagnostic criteria for alcohol-related birth defects; an updated comprehensive research dysmorphology scoring system; and a new lip/philtrum guide for the white population, incorporating a 45-degree view. The guidelines reflect consensus among a large and experienced cadre of FASD investigators in the fields of dysmorphology, epidemiology, neurology, psychology, developmental/behavioral pediatrics, and educational diagnostics. Their improved clarity and specificity will guide clinicians in accurate diagnosis of infants and children prenatally exposed to alcohol. C1 [Hoyme, H. Eugene; Elliott, Amy J.; May, Philip A.] Sanford Res, Sioux Falls, SD USA. [Hoyme, H. Eugene; Elliott, Amy J.; May, Philip A.] Univ South Dakota, Dept Pediat, Sanford Sch Med, Sioux Falls, SD USA. [Hoyme, H. Eugene] Univ Arizona, Coll Med, Ctr Appl Genet & Genom, Tucson, AZ USA. [Hoyme, H. Eugene] Univ Arizona, Coll Med, Dept Pediat, Tucson, AZ USA. [Kalberg, Wendy O.; Blankenship, Jason; Buckley, David; May, Philip A.] Univ New Mexico, Ctr Alcoholism Substance Abuse & Addict, Albuquerque, NM 87131 USA. [Marais, Anna-Susan] Univ Stellenbosch, Fac Med & Hlth Sci, Stellenbosch, South Africa. [Manning, Melanie A.] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA. [Manning, Melanie A.] Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA. [Robinson, Luther K.] SUNY Buffalo, Sch Med & Biomed Sci, Dept Pediat, Buffalo, NY 14260 USA. [Adam, Margaret P.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. [Abdul-Rahman, Omar] Univ Mississippi, Sch Med, Dept Pediat, Jackson, MS 39216 USA. [Jewett, Tamison] Wake Forest Univ, Sch Med, Dept Pediat, Winston Salem, NC 27109 USA. [Coles, Claire D.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. [Chambers, Christina; Jones, Kenneth L.] Univ Calif San Diego, Sch Med, Dept Pediat, La Jolla, CA 92093 USA. [Adnams, Colleen M.] Univ Cape Town, Fac Hlth Sci, Dept Psychiat & Mental Hlth, Cape Town, South Africa. [Shah, Prachi E.] Univ Michigan, Sch Med, Dept Pediat & Communicable Dis, Ann Arbor, MI USA. [Riley, Edward P.] San Diego State Univ, Dept Psychol, San Diego, CA 92182 USA. [Charness, Michael E.] Harvard Med Sch, Dept Neurol, VA Boston Healthcare Syst, Boston, MA USA. [Charness, Michael E.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Warren, Kenneth R.] NIAAA, Bethesda, MD USA. [May, Philip A.] Univ N Carolina, Dept Nutr, Gillings Sch Global Publ Hlth, Inst Nutr Res, Chapel Hill, NC USA. RP Hoyme, HE (reprint author), Sanford Hlth, Genet & Genom Med, POB 5039, Sioux Falls, SD 57117 USA. EM gene.hoyme@sanfordhealth.org FU National Institutes of Health (NIH): National Institute on Alcohol Abuse and Alcoholism [R01 AA11685, R01/U01 AA01115134, U01 AA019879-01/NIH-NIAAA]; Oxnard Foundation, Newport Beach, CA; National Institutes of Health (NIH) FX This project was funded by the National Institutes of Health (NIH): National Institute on Alcohol Abuse and Alcoholism grants R01 AA11685, R01/U01 AA01115134, and U01 AA019879-01/NIH-NIAAA (Collaboration on Fetal Alcohol Spectrum Disorders Prevalence); and by the Oxnard Foundation, Newport Beach, CA. Funded by the National Institutes of Health (NIH). NR 112 TC 4 Z9 4 U1 19 U2 20 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD AUG PY 2016 VL 138 IS 2 AR e20154256 DI 10.1542/peds.2015-4256 PG 18 WC Pediatrics SC Pediatrics GA DS7ZP UT WOS:000381002500017 ER PT J AU Reisman, J Arlington, L Jensen, L Louis, H Suarez-Rebling, D Nelson, BD AF Reisman, Jonathan Arlington, Lauren Jensen, Lloyd Louis, Henry Suarez-Rebling, Daniela Nelson, Brett D. TI Newborn Resuscitation Training in Resource-Limited Settings: A Systematic Literature Review SO PEDIATRICS LA English DT Review ID HELPING BABIES BREATHE; EMERGENCY CARDIOVASCULAR CARE; NEONATAL RESUSCITATION; EDUCATIONAL INTERVENTION; RURAL ETHIOPIA; CARDIOPULMONARY-RESUSCITATION; PEDIATRIC RESIDENTS; COGNITIVE KNOWLEDGE; FRONTLINE PROVIDERS; BIRTH ATTENDANTS AB CONTEXT: Birth asphyxia contributes substantially to neonatal mortality in low-and middle-income countries (LMICs). The effects of training birth attendants in neonatal resuscitation (NR) on mortality are limited by falloff of skills and knowledge over time and transference of learned skills into clinical practice. OBJECTIVE: This review examined acquisition and retention of NR knowledge and skills by birth attendants in LMICs and the effectiveness of interventions to improve them. DATA SOURCES: Medline, Cochrane, Embase, CINAHL, Bireme, and African Index Medicus databases were searched. We reviewed Web pages and reports from non-peer-reviewed (or "gray") literature sources addressing NR training in LMICs. STUDY SELECTION: Articles on acquisition and retention of NR knowledge and skills, and interventions to improve them, were limited to LMICs. RESULTS: The initial search identified 767 articles, of which 45 met all inclusion criteria. Of these, 31 articles analyzed acquisition of knowledge and skills, and 19 analyzed retention. Most studies found high acquisition rates, although birth attendants struggled to learn bag-mask ventilation. Although significant falloff of knowledge and skills occurred after training, refresher training seemed to improve retention. Results of the gray literature analysis suggest that formal, structured practice sessions improve retention. LIMITATIONS: This review did not analyze training's direct impact on mortality. CONCLUSIONS: Knowledge and skills falloff is a significant barrier to the success of NR training programs and possibly to reducing newborn mortality in LMICs. Refresher training and structured practice show significant promise. Additional research is needed to implement and assess retention improvement strategies in classroom and clinical settings. C1 [Reisman, Jonathan] Childrens Hosp Philadelphia, Div Emergency Med, 34th St & Civ Ctr Blvd, Philadelphia, PA 19104 USA. [Reisman, Jonathan; Arlington, Lauren; Louis, Henry; Suarez-Rebling, Daniela; Nelson, Brett D.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Reisman, Jonathan; Nelson, Brett D.] Harvard Med Sch, Boston, MA USA. [Jensen, Lloyd] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA. RP Reisman, J (reprint author), Childrens Hosp Philadelphia, Div Emergency Med, 34th St & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM reisman.jonathan@gmail.com OI Nelson, Brett/0000-0002-5049-1798 FU Children's Investment Fund FX Funding for this study was provided by the Children's Investment Fund. NR 80 TC 0 Z9 0 U1 7 U2 7 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD AUG PY 2016 VL 138 IS 2 AR e20154490 DI 10.1542/peds.2015-4490 PG 16 WC Pediatrics SC Pediatrics GA DS7ZP UT WOS:000381002500025 ER PT J AU Giannikou, K Malinowska, IA Pugh, TJ Yan, R Tseng, YY Oh, C Kim, J Tyburczy, ME Chekaluk, Y Liu, Y Alesi, N Finlay, GA Wu, CL Signoretti, S Meyerson, M Getz, G Boehm, JS Henske, EP Kwiatkowski, DJ AF Giannikou, Krinio Malinowska, Izabela A. Pugh, Trevor J. Yan, Rachel Tseng, Yuen-Yi Oh, Coyin Kim, Jaegil Tyburczy, Magdalena E. Chekaluk, Yvonne Liu, Yang Alesi, Nicola Finlay, Geraldine A. Wu, Chin-Lee Signoretti, Sabina Meyerson, Matthew Getz, Gad Boehm, Jesse S. Henske, Elizabeth P. Kwiatkowski, David J. TI Whole Exome Sequencing Identifies TSC1/TSC2 Biallelic Loss as the Primary and Sufficient Driver Event for Renal Angiomyolipoma Development SO PLOS GENETICS LA English DT Article ID TUBEROUS SCLEROSIS COMPLEX; SPORADIC PULMONARY LYMPHANGIOLEIOMYOMATOSIS; ANALYSIS TOOLKIT; CANCER GENOMICS; TSC2; MUTATIONS; TUMOR; MTOR; GENE; HETEROZYGOSITY AB Renal angiomyolipoma is a kidney tumor in the perivascular epithelioid (PEComa) family that is common in patients with Tuberous Sclerosis Complex (TSC) and Lymphangioleiomyomatosis (LAM) but occurs rarely sporadically. Though histologically benign, renal angiomyolipoma can cause life-threatening hemorrhage and kidney failure. Both angiomyolipoma and LAM have mutations in TSC2 or TSC1. However, the frequency and contribution of other somatic events in tumor development is unknown. We performed whole exome sequencing in 32 resected tumor samples (n = 30 angiomyolipoma, n = 2 LAM) from 15 subjects, including three with TSC. Two germline and 22 somatic inactivating mutations in TSC2 were identified, and one germline TSC1 mutation. Twenty of 32 (62%) samples showed copy neutral LOH (CN-LOH) in TSC2 or TSC1 with at least 8 different LOH regions, and 30 of 32 (94%) had biallelic loss of either TSC2 or TSC1. Whole exome sequencing identified a median of 4 somatic non-synonymous coding region mutations (other than in TSC2/TSC1), a mutation rate lower than nearly all other cancer types. Three genes with mutations were known cancer associated genes (BAP1, ARHGAP35 and SPEN), but they were mutated in a single sample each, and were missense variants with uncertain functional effects. Analysis of sixteen angiomyolipomas from a TSC subject showed both second hit point mutations and CN-LOH in TSC2, many of which were distinct, indicating that they were of independent clonal origin. However, three tumors had two shared mutations in addition to private somatic mutations, suggesting a branching evolutionary pattern of tumor development following initiating loss of TSC2. Our results indicate that TSC2 and less commonly TSC1 alterations are the primary essential driver event in angiomyolipoma/LAM, whereas other somatic mutations are rare and likely do not contribute to tumor development. C1 [Giannikou, Krinio; Malinowska, Izabela A.; Yan, Rachel; Tyburczy, Magdalena E.; Chekaluk, Yvonne; Liu, Yang; Alesi, Nicola; Signoretti, Sabina; Henske, Elizabeth P.; Kwiatkowski, David J.] Harvard Med Sch, Brigham & Womens Hosp, Div Pulm & Crit Care Med & Genet, Boston, MA 02115 USA. [Pugh, Trevor J.; Tseng, Yuen-Yi; Oh, Coyin; Kim, Jaegil; Meyerson, Matthew; Getz, Gad; Boehm, Jesse S.; Henske, Elizabeth P.; Kwiatkowski, David J.] Broad Inst Harvard & MIT, Cambridge, MA 02139 USA. [Finlay, Geraldine A.] Tufts Univ New England Med Ctr, Boston, MA USA. [Wu, Chin-Lee] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Henske, EP; Kwiatkowski, DJ (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Div Pulm & Crit Care Med & Genet, Boston, MA 02115 USA.; Henske, EP; Kwiatkowski, DJ (reprint author), Broad Inst Harvard & MIT, Cambridge, MA 02139 USA. EM EHENSKE@BWH.HARVARD.EDU; dk@rics.bwh.harvard.edu OI Oh, Coyin/0000-0002-5732-3471 FU NIH NHLBI RCI [HL100655]; NIH NCI [1P01CA120964]; Broad Institute Scientific Projects to Accelerate Research and Collaboration (SPARC) program; Engles Fund for TSC and LAM Research FX Funding sources for this work are: NIH NHLBI RCI HL100655; NIH NCI 1P01CA120964; the Broad Institute Scientific Projects to Accelerate Research and Collaboration (SPARC) program; and the Engles Fund for TSC and LAM Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 3 Z9 3 U1 6 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD AUG PY 2016 VL 12 IS 8 AR e1006242 DI 10.1371/journal.pgen.1006242 PG 18 WC Genetics & Heredity SC Genetics & Heredity GA DU7LA UT WOS:000382394500038 ER PT J AU Heilbronner, S Monk, IR Brozyna, JR Heinrichs, DE Skaar, EP Peschel, A Foster, TJ AF Heilbronner, Simon Monk, Ian R. Brozyna, Jeremy R. Heinrichs, David E. Skaar, Eric P. Peschel, Andreas Foster, Timothy J. TI Competing for Iron: Duplication and Amplification of the isd Locus in Staphylococcus lugdunensis HKU09-01 Provides a Competitive Advantage to Overcome Nutritional Limitation SO PLOS GENETICS LA English DT Article ID GENE AMPLIFICATION; HAEMOPHILUS-INFLUENZAE; GENOME SEQUENCE; B LOCUS; AUREUS; RESISTANCE; EVOLUTION; HEME; ACQUISITION; TRANSPOSON AB Staphylococcus lugdunensis is a coagulase negative bacterial pathogen that is particularly associated with severe cases of infectious endocarditis. Unique amongst the coagulase-negative staphylococci, S. lugdunensis harbors an iron regulated surface determinant locus (isd). This locus facilitates the acquisition of heme as a source of nutrient iron during infection and allows iron limitation caused by "nutritional immunity" to be overcome. The isd locus is duplicated in S. lugdunensis HKU09-01 and we show here that the duplication is intrinsically unstable and undergoes accordion-like amplification and segregation leading to extensive isd copy number variation. Amplification of the locus increased the level of expression of Isd proteins and improved binding of hemoglobin to the cell surface of S. lugdunensis. Furthermore, Isd overexpression provided an advantage when strains were competing for a limited amount of hemoglobin as the sole source of iron. Gene duplications and amplifications (GDA) are events of fundamental importance for bacterial evolution and are frequently associated with antibiotic resistance in many species. As such, GDAs are regarded as evolutionary adaptions to novel selective pressures in hostile environments pointing towards a special importance of isd for S. lugdunensis. For the first time we show an example of a GDA that involves a virulence factor of a Gram-positive pathogen and link the GDA directly to a competitive advantage when the bacteria were struggling with selective pressures mimicking "nutritional immunity". C1 [Heilbronner, Simon; Monk, Ian R.; Foster, Timothy J.] Trinity Coll Dublin, Dept Microbiol, Dublin, Ireland. [Heilbronner, Simon; Peschel, Andreas] Univ Tubingen, Interfac Inst Microbiol & Infect Med, Infect Biol, Tubingen, Germany. [Monk, Ian R.] Univ Melbourne, Doherty Inst Infect & Immun, Dept Microbiol & Immunol, Parkville, Vic, Australia. [Brozyna, Jeremy R.; Heinrichs, David E.] Univ Western Ontario, Dept Microbiol & Immunol, London, ON, Canada. [Skaar, Eric P.] Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37212 USA. [Skaar, Eric P.] Tennessee Valley Healthcare Syst, US Dept Vet Affairs, Nashville, TN USA. RP Heilbronner, S (reprint author), Trinity Coll Dublin, Dept Microbiol, Dublin, Ireland.; Heilbronner, S (reprint author), Univ Tubingen, Interfac Inst Microbiol & Infect Med, Infect Biol, Tubingen, Germany. EM simon.heilbronner@uni-tuebingen.de OI Monk, Ian/0000-0001-6982-8074 FU Irish Research Council for Science, Engineering and Technology [RS2000192]; Science Foundation Ireland [08/IN.1/B1854]; German Academic exchange (DAAD) [50722682]; European Research Council [GA 655978]; German Research Council [SFB766]; NIH [R01 AI069233, R01 AI073843]; Department of Veterans Affairs [INFB-024-13F]; Canadian Institutes of Health Research [MOP-38002]; Deutsche Forschungsgemeinschaft; "Open Access Publishing Fund" of the University of Tubingen FX We acknowledge the support of the Irish Research Council for Science, Engineering and Technology for an Embark scholarship (RS2000192) to SH (http://www.research.ie/. We acknowledge the support of the Science Foundation Ireland for a Programme Investigator grant (08/IN.1/B1854) to TJF (http://www.sfi.ie/). We acknowledge the support of the German Academic exchange (DAAD) for a stipend for the "retrieval of German Scientist working abroad" (50722682) to SH (https://www.daad.de/en/). We acknowledge the support of the European Research Council for their support by providing a MSC-individual fellowship (GA 655978) to SH (https://erc.europa.eu/). Work in the laboratory of AP was supported by the SFB766 grant from the German Research Council (http://www.dfg.de/en/). Work in the laboratory of EPS is supported by NIH R01 AI069233 and R01 AI073843 (http://grants.nih.gov/grants/oer.htm) and Department of Veterans Affairs Merit Award INFB-024-13F (http://www.research.va.gov/default.cfm). Work in the laboratory of DEH is supported by Canadian Institutes of Health Research grant MOP-38002 (http://www.cihr-irsc.gc.ca/e/193.html). We acknowledge support by "Deutsche Forschungsgemeinschaft" and the "Open Access Publishing Fund" of the University of Tubingen. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 0 Z9 0 U1 4 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD AUG PY 2016 VL 12 IS 8 AR e1006246 DI 10.1371/journal.pgen.1006246 PG 25 WC Genetics & Heredity SC Genetics & Heredity GA DU7LA UT WOS:000382394500041 PM 27575058 ER PT J AU Li, A Makar, RS Hurwitz, S Uhl, L Kaufman, RM Stowell, CP Dzik, WS Bendapudi, PK AF Li, Ang Makar, Robert S. Hurwitz, Shelley Uhl, Lynne Kaufman, Richard M. Stowell, Christopher P. Dzik, Walter S. Bendapudi, Pavan K. TI Treatment with or without plasma exchange for patients with acquired thrombotic microangiopathy not associated with severe ADAMTS13 deficiency: a propensity score-matched study SO TRANSFUSION LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; VON-WILLEBRAND-FACTOR; FACTOR-CLEAVING PROTEASE; THROMBOCYTOPENIC PURPURA; EXPERIENCE; SUBSTRATE; DIAGNOSIS; OUTCOMES; ASSAY; VWF AB BACKGROUNDTherapeutic plasma exchange (TPE) is a proven treatment for thrombotic thrombocytopenic purpura (TTP) characterized by severe ADAMTS13 deficiency, but the efficacy of TPE in suspected TTP with an ADAMTS13 activity level of more than 10% remains controversial. STUDY DESIGN AND METHODSWe conducted a propensity score (PS)-matched study of 186 adult patients included in the Harvard Thrombotic Microangiopathy (TMA) Research Collaborative registry who presented with TMA suggestive of TTP but an ADAMTS13 activity level of more than 10%. RESULTSBefore matching, patients treated with TPE (n=71) differed from untreated patients (n=115) by several clinical measures. PS matching was performed to address clinical disparities between the two groups and resulted in a well-balanced cohort of 59 TPE-treated patients paired with 59 untreated controls, all of whom had TMA. After matching, we observed no significant difference in the primary outcome of 90-day survival between the treated and untreated groups (hazard ratio, 0.88; 95% confidence interval [CI], 0.44-1.77; p=0.72). In-hospital mortality (odds ratio [OR], 0.77; 95% CI, 0.34-1.75; p=0.53) and the percentage of patients with platelet count recovery (OR, 1.58; 95% CI, 0.77-3.26; p=0.21) also did not differ significantly between the two matched groups. CONCLUSIONOur data suggest that routine use of TPE in the diverse group of TMA patients without severe ADAMTS13 deficiency may not significantly improve outcomes. C1 [Li, Ang] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Makar, Robert S.; Stowell, Christopher P.; Dzik, Walter S.; Bendapudi, Pavan K.] Massachusetts Gen Hosp, Dept Pathol, Blood Transfus Serv, Boston, MA 02114 USA. [Dzik, Walter S.; Bendapudi, Pavan K.] Massachusetts Gen Hosp, Div Hematol, Yawkey 7,55 Fruit St, Boston, MA 02114 USA. [Hurwitz, Shelley] Brigham & Womens Hosp, Ctr Clin Invest, 75 Francis St, Boston, MA 02115 USA. [Kaufman, Richard M.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Uhl, Lynne] Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Brookline Ave, Boston, MA 02215 USA. [Li, Ang; Makar, Robert S.; Hurwitz, Shelley; Uhl, Lynne; Kaufman, Richard M.; Stowell, Christopher P.; Dzik, Walter S.; Bendapudi, Pavan K.] Harvard Med Sch, Boston, MA USA. RP Bendapudi, PK (reprint author), Massachusetts Gen Hosp, Div Hematol, Yawkey 7,55 Fruit St, Boston, MA 02114 USA. EM pkbendapudi@partners.org FU Luick Family Fund of the Massachusetts General Hospital; American Society of Hematology HONORS Program FX This work was generously supported by the Luick Family Fund of the Massachusetts General Hospital and the American Society of Hematology HONORS Program (AL). NR 31 TC 2 Z9 2 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 AUG PY 2016 VL 56 IS 8 BP 2069 EP 2077 DI 10.1111/trf.13654 PG 9 WC Hematology SC Hematology GA DU8ZP UT WOS:000382506100022 PM 27232383 ER PT J AU Gutierrez-Martinez, P Rossi, DJ Beerman, I AF Gutierrez-Martinez, Paula Rossi, Derrick J. Beerman, Isabel TI DNA Damage and Aging Around the Clock SO TRENDS IN MOLECULAR MEDICINE LA English DT Editorial Material ID HEMATOPOIETIC STEM-CELLS; SELF-RENEWAL AB The hematopoietic system undergoes many changes during aging, but the causes and molecular mechanisms behind these changes are not well understood. Wang et al. have recently implicated a circadian rhythm gene, Per2, as playing a role in the DNA damage response and in the expression of lymphoid genes in aged hematopoietic stem cells. C1 [Gutierrez-Martinez, Paula; Rossi, Derrick J.; Beerman, Isabel] Boston Childrens Hosp, Div Hematol Oncol, Program Cellular & Mol Med, Boston, MA USA. [Gutierrez-Martinez, Paula; Rossi, Derrick J.; Beerman, Isabel] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA USA. [Rossi, Derrick J.] Harvard Med Sch, Dept Pediat, Boston, MA USA. [Rossi, Derrick J.] Harvard Stem Cell Inst, Cambridge, MA USA. RP Beerman, I (reprint author), Boston Childrens Hosp, Div Hematol Oncol, Program Cellular & Mol Med, Boston, MA USA.; Beerman, I (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA USA. EM Isabel.Beerman@childrens.harvard.edu FU NHLBI NIH HHS [U01 HL099997, R01 HL107630, U19 HL129903, U01 HL107440]; NIA NIH HHS [K01 AG050813]; NIDDK NIH HHS [UC4 DK104218] NR 10 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 1471-4914 EI 1471-499X J9 TRENDS MOL MED JI Trends Mol. Med PD AUG PY 2016 VL 22 IS 8 BP 635 EP 637 DI 10.1016/j.molmed.2016.06.006 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA DT5NR UT WOS:000381530400003 PM 27345866 ER PT J AU Westring, A McDonald, JM Carr, P Grisso, JA AF Westring, Alyssa McDonald, Jennifer M. Carr, Phyllis Grisso, Jeane Ann TI An Integrated Framework for Gender Equity in Academic Medicine SO ACADEMIC MEDICINE LA English DT Editorial Material ID FACULTY; CULTURE AB In 2008, the National Institutes of Health funded 14 R01 grants to study causal factors that promote and support women's biomedical careers. The Research Partnership on Women in Biomedical Careers, a multi-institutional collaboration of the investigators, is one product of this initiative. A comprehensive framework is needed to address change at many levels-department, institution, academic community, and beyond-and enable gender equity in the development of successful biomedical careers. The authors suggest four distinct but interrelated aspects of culture conducive to gender equity: equal access to resources and opportunities, minimizing unconscious gender bias, enhancing work-life balance, and leadership engagement. They review the collection of eight articles in this issue, which each address one or more of the four dimensions of culture. The articles suggest that improving mentormentee fit, coaching grant reviewers on unconscious bias, and providing equal compensation and adequate resources for career development will contribute positively to gender equity in academic medicine. Academic medicine must adopt an integrated perspective on culture for women and acknowledge the multiple facets essential to gender equity. To effect change, culture must be addressed both within and beyond academic health centers (AHCs). Leaders within AHCs must examine their institutions' processes, resources, and assessment for fairness and transparency; mobilize personnel and financial resources to implement evidence-based initiatives; and assign accountability for providing transparent progress assessments. Beyond AHCs, organizations must examine their operations and implement change to ensure parity of funding, research, and leadership opportunities as well as transparency of assessment and accreditation. C1 [Westring, Alyssa] Depaul Univ, Management, Driehaus Coll Business, Chicago, IL 60604 USA. [Carr, Phyllis] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Carr, Phyllis] Harvard Med Sch, Boston, MA USA. [Grisso, Jeane Ann] Univ Penn, Med, Publ Hlth, Philadelphia, PA 19104 USA. RP Westring, A (reprint author), 1 E Jackson Blvd, Chicago, IL 60604 USA. EM awestrin@depaul.edu NR 20 TC 2 Z9 2 U1 7 U2 7 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 AUG PY 2016 VL 91 IS 8 BP 1041 EP 1044 DI 10.1097/ACM.0000000000001275 PG 4 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA DS5HT UT WOS:000380813000010 PM 27276008 ER PT J AU Freund, KM Raj, A Kaplan, SE Terrin, N Breeze, JL Urech, TH Carr, PL AF Freund, Karen M. Raj, Anita Kaplan, Samantha E. Terrin, Norma Breeze, Janis L. Urech, Tracy H. Carr, Phyllis L. TI Inequities in Academic Compensation by Gender: A Follow-up to the National Faculty Survey Cohort Study SO ACADEMIC MEDICINE LA English DT Article ID PART-TIME; PHYSICIAN-RESEARCHERS; SEX-DIFFERENCES; MEDICINE; NEGOTIATION; EQUITY; SALARY; ADVANCEMENT; WOMEN; PRODUCTIVITY AB Purpose Cross-sectional studies have demonstrated gender differences in salaries within academic medicine. No research has assessed longitudinal compensation patterns. This study sought to assess longitudinal patterns by gender in compensation, and to understand factors associated with these differences in a longitudinal cohort. Method A 17-year longitudinal follow-up of the National Faculty Survey was conducted with a random sample of faculty from 24 U.S. medical schools. Participants employed full-time at initial and follow-up time periods completed the survey. Annual pretax compensation during academic year 2012-2013 was compared by gender. Covariates assessed included race/ethnicity; years since first academic appointment; retention in academic career; academic rank; departmental affiliation; percent effort distribution across clinical, teaching, administrative, and research duties; marital and parental status; and any leave or part-time status in the years between surveys. Results In unadjusted analyses, women earned a mean of $20,520 less than men (P = .03); women made 90 cents for every dollar earned by their male counterparts. This difference was reduced to $16,982 (P = .04) after adjusting for covariates. The mean difference of $15,159 was no longer significant (P = .06) when adjusting covariates and for those who had ever taken a leave or worked part-time. Conclusions The continued gender gap in compensation cannot be accounted for by metrics used to calculate salary. Institutional actions to address these disparities include both initial appointment and annual salary equity reviews, training of senior faculty and administrators to understand implicit bias, and training of women faculty in negotiating skills. C1 [Freund, Karen M.] Tufts Univ, Sch Med, Med Ctr, Med, Boston, MA 02111 USA. [Raj, Anita] Univ Calif San Diego, Sch Med, Med & Global Publ Hlth, La Jolla, CA 92093 USA. [Raj, Anita] Univ Calif San Diego, Sch Med, Ctr Gender Equ & Hlth, La Jolla, CA 92093 USA. [Kaplan, Samantha E.] Boston Univ, Sch Med, Divers, Boston, MA 02118 USA. [Terrin, Norma; Breeze, Janis L.] Tufts Clin & Translat Sci Inst, Biostat Epidemiol & Res Design Ctr, Boston, MA USA. [Terrin, Norma; Breeze, Janis L.] Tufts Med Ctr, Boston, MA 02111 USA. [Urech, Tracy H.] VA Palo Alto Healthcare Syst, VA HSR&D Ctr Innovat Implementat, Palo Alto, CA USA. [Carr, Phyllis L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Carr, Phyllis L.] Harvard Med Sch, Boston, MA USA. RP Freund, KM (reprint author), Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, 800 Washington St,Box 63, Boston, MA 02111 USA. EM kfreund@tuftsmedicalcenter.org FU National Institute of General Medical Sciences [R01 GM088470]; Office of Research in Women's Health, National Institutes of Health FX The project described was supported by award number R01 GM088470 from the National Institute of General Medical Sciences and Office of Research in Women's Health, National Institutes of Health. NR 26 TC 9 Z9 9 U1 6 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 AUG PY 2016 VL 91 IS 8 BP 1068 EP 1073 DI 10.1097/ACM.0000000000001250 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA DS5HT UT WOS:000380813000018 PM 27276007 ER PT J AU Raj, A Carr, PL Kaplan, SE Terrin, N Breeze, JL Freund, KM AF Raj, Anita Carr, Phyllis L. Kaplan, Samantha E. Terrin, Norma Breeze, Janis L. Freund, Karen M. TI Longitudinal Analysis of Gender Differences in Academic Productivity Among Medical Faculty Across 24 Medical Schools in the United States SO ACADEMIC MEDICINE LA English DT Article ID RESEARCH GRANT APPLICATIONS; SEX-DIFFERENCES; RESPONSIBILITIES; HOSPITALISTS; SATISFACTION; RESEARCHERS; DISPARITIES; AUTHORSHIP; RESIDENTS; WOMEN AB Purpose To examine gender differences in academic productivity, as indicated by publications and federal grant funding acquisition, among a longitudinal cohort of medical faculty from 24 U.S. medical schools, 1995 to 2012-2013. Method Data for this research were taken from the National Faculty Survey involving a survey with medical faculty recruited from medical schools in 1995, and followed up in 2012-2013. Data included surveys and publication and grant funding databases. Outcomes were number of publications, h-index, and principal investigator on a federal grant in the prior two years. Gender differences were assessed using negative binomial regression models for publication and h-index outcomes, and logistic regression for the grant funding outcome; analyses adjusted for race/ethnicity, rank, specialty area, and years since first academic appointment. Results Data were available for 1,244 of the 1,275 (98%) subjects eligible for the follow-up study. Men were significantly more likely than women to be married/partnered, have children, and hold the rank of professor (P < .0001). Adjusted regression models documented that women had a lower rate of publication (relative number = 0.71; 95% CI = 0.63, 0.81; P < .0001) and h-index (relative number = 0.81; 95% CI = 0.73, 0.90; P < .0001) relative to men, but there was no gender difference in grant funding. Conclusions Women faculty acquired federal funding at similar rates as male faculty, yet lagged behind in terms of publications and their impact. Medical academia must consider how to help address ongoing gender disparities in publication records. C1 [Raj, Anita] Univ Calif San Diego, Sch Med, Med & Global Publ Hlth, San Diego, CA 92103 USA. [Raj, Anita] Univ Calif San Diego, Sch Med, Ctr Gender Equ & Hlth, San Diego, CA 92103 USA. [Carr, Phyllis L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Carr, Phyllis L.] Harvard Med Sch, Boston, MA USA. [Kaplan, Samantha E.] Boston Univ, Sch Med, Divers, Boston, MA 02118 USA. [Terrin, Norma; Breeze, Janis L.] Tufts Clin & Translat Sci Inst, Biostat Epidemiol & Res Design Ctr, Boston, MA USA. [Terrin, Norma; Breeze, Janis L.] Tufts Med Ctr, Boston, MA 02111 USA. [Freund, Karen M.] Tufts Univ, Sch Med, Med, Tufts Med Ctr, Boston, MA 02111 USA. RP Freund, KM (reprint author), Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, 800 Washington St,Box 63, Boston, MA 02111 USA. EM kfreund@tuftsmedicalcenter.org FU National Institute of General Medical Sciences [R01GM088470]; Office of Research in Women's Health, National Institutes of Health FX The project described was supported by award number R01GM088470 from the National Institute of General Medical Sciences and Office of Research in Women's Health, National Institutes of Health. NR 26 TC 6 Z9 6 U1 4 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 AUG PY 2016 VL 91 IS 8 BP 1074 EP 1079 DI 10.1097/ACM.0000000000001251 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA DS5HT UT WOS:000380813000019 PM 27276002 ER PT J AU West, RK Ravona-Springer, R Heymann, A Schmeidler, J Leroith, D Koifman, K D'Arcy, RCN Song, XW Guerrero-Berroa, E Preiss, R Hoffman, H Sano, M Silverman, JM Schnaider-Beeri, M AF West, Rebecca K. Ravona-Springer, Ramit Heymann, Anthony Schmeidler, James Leroith, Derek Koifman, Keren D'Arcy, Ryan C. N. Song, Xiaowei Guerrero-Berroa, Elizabeth Preiss, Rachel Hoffman, Hadas Sano, Mary Silverman, Jeremy M. Schnaider-Beeri, Michal TI Waist circumference is correlated with poorer cognition in elderly type 2 diabetes women SO ALZHEIMERS & DEMENTIA LA English DT Article DE Cognitive performance; Waist circumference; Type 2 diabetes mellitus; Risk factors; Dementia ID RISK-FACTORS; CARDIOVASCULAR RISK; DEMENTIA; IMPAIRMENT; OLDER; ASSOCIATION; ADIPOSITY; OBESITY; DECLINE AB Introduction: Waist circumference is associated with type 2 diabetes (T2D) and cognition, yet the relationship between waist circumference and cognition in individuals with T2D is not well understood. Methods: We studied the relationship of waist circumference with five cognitive outcomes (executive functioning, language/semantic categorization, attention/working memory, episodic memory, and an overall cognition measure) in 845 cognitively normal elderly with type 2 diabetes (T2D). esults: In women, waist circumference was correlated with significantly lower language and/or semantic categorization performance (P < .0001), executive functioning (P = .026), and overall cognition (P = .003) after controlling for age, education, BMI, and cardiovascular, diabetes related, APOE 64, and inflammatory potential confounders. Attention/working memory (P = .532) and episodic memory (P = .144) were not associated with waist circumference. These correlations were not found in men. Discussion: These results suggest that central adiposity in elderly women with T2D may increase their risk for dementia. (C) 2016 Published by Elsevier Inc. on behalf of The Alzheimer's Association. C1 [West, Rebecca K.; Schmeidler, James; Guerrero-Berroa, Elizabeth; Sano, Mary; Silverman, Jeremy M.; Schnaider-Beeri, Michal] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Ravona-Springer, Ramit; Koifman, Keren; Preiss, Rachel; Hoffman, Hadas; Schnaider-Beeri, Michal] Sheba Med Ctr, Joseph Sagol Neurosci Ctr, Ramat Gan, Israel. [Heymann, Anthony] Maccabi Healthcare Serv, Tel Aviv, Israel. [Heymann, Anthony] Tel Aviv Univ, Sackler Sch Med, Dept Family Med, Tel Aviv, Israel. [Leroith, Derek] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [D'Arcy, Ryan C. N.; Song, Xiaowei] Simon Fraser Univ, Metro Vancouver, BC, Canada. [D'Arcy, Ryan C. N.; Song, Xiaowei] Fraser Hlth, Surrey Mem Hosp, Metro Vancouver, BC, Canada. [Guerrero-Berroa, Elizabeth; Sano, Mary; Silverman, Jeremy M.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP West, RK (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. EM rebecca.west@mssm.edu FU MA grants [R01 AG034087, P50 AG05138]; Helen Bader Foundation; Alzheimer's Association [MNIRGD-14-321113]; Irma T. Hirschl Scholar award FX This study was supported by MA grants R01 AG034087 to Dr. Beeri and P50 AG05138 to Dr. Sano, the Helen Bader Foundation, and the Alzheimer's Association grant MNIRGD-14-321113 to Dr. Guerrero-Berroa, and the Irma T. Hirschl Scholar award to Dr. Beeri. NR 20 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 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD AUG PY 2016 VL 12 IS 8 BP 925 EP 929 DI 10.1016/j.jalz.2016.03.017 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA DT1ND UT WOS:000381248500009 PM 27149905 ER PT J AU McIlvennan, CK Swetz, KM AF McIlvennan, Colleen K. Swetz, Keith M. TI Lack of Agreement With What We Think Is Right Does Not Necessarily Equal an Ethical Problem: Respecting Patients' Goals of Care SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material ID LIFE; END; PERSPECTIVES; DEVICE C1 [McIlvennan, Colleen K.] Univ Colorado, Sch Med, Boulder, CO 80309 USA. [Swetz, Keith M.] Univ Alabama, Sch Med, Tuscaloosa, AL 35487 USA. [Swetz, Keith M.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Swetz, KM (reprint author), UAB Ctr Palliat & Support Care, 1720 2nd Ave South BDB 650, Birmingham, AL 35294 USA. EM kswetz@uabmc.edu NR 10 TC 1 Z9 1 U1 1 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1526-5161 EI 1536-0075 J9 AM J BIOETHICS JI Am. J. Bioeth. PD AUG PY 2016 VL 16 IS 8 BP 13 EP 15 DI 10.1080/15265161.2016.1187220 PG 3 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA DS6OI UT WOS:000380901100006 PM 27366837 ER PT J AU Blosnich, JR Brenner, LA Bossarte, RM AF Blosnich, John R. Brenner, Lisa A. Bossarte, Robert M. TI Population mental health among US military veterans: results of the Veterans Health Module of the Behavioral Risk Factor Surveillance System, 2011-2012 SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Veterans health; Suicidal ideation; Attempted suicide; Mental health services ID SUICIDE MORTALITY; UNITED-STATES; IDEATION; SERVICE; HISTORY AB Purpose: To examine mental health indicators, in aggregate and stratified by sex, among a population based sample of U.S. military veterans. Methods: Data are from veteran who completed the Veterans Health Module (VHM) of the 2011 and 2012 Behavioral Risk Factor Surveillance System (n = 10,406). VHM items included lifetime diagnoses of mental illnesses, service in a combat zone, sources of mental health care, and past 12-month suicidal ideation and attempt. We used weighted, multiple logistic regression models, adjusted for sociodemographics, to examine differences in suicidal ideation and attempt among men and women. Results: Overall, 5.0% of the sample reported recent suicidal ideation and 1.0% reported attempting suicide. Among men, unemployment was positively associated with suicidal ideation, and combat exposure was negatively associated with suicidal ideation. Being separated, divorced, or widowed was positively associated with suicidal ideation among women. After adjusting for sociodemographic and VHM variables, veterans who sought mental health treatment from both Veterans Affairs (VA) and non-VA facilities had more than fourfold increased odds of suicidal ideation than veteran who sought mental health treatment from only VA facilities (adjusted odds ratio = 4.02; 95% confidence interval 1.23-13.13). Conclusions: Correlates of suicidal ideation differ between male and female veterans. Veterans who use both non-VA and VA facilities for mental health services may have greater risk of self-directed violence. Published by Elsevier Inc. C1 [Blosnich, John R.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Brenner, Lisa A.] Rocky Mt Mental Illness Res Educ & Clin Ctr, Denver, CO USA. [Brenner, Lisa A.] Univ Colorado, Anschutz Sch Med, Dept Psychiat, Aurora, CO USA. [Brenner, Lisa A.] Univ Colorado, Anschutz Sch Med, Dept Neurol, Aurora, CO USA. [Brenner, Lisa A.] Univ Colorado, Anschutz Sch Med, Dept Phys Med & Rehabil, Aurora, CO USA. [Bossarte, Robert M.] US Dept Vet Affairs, Post Deployment Hlth Serv, Washington, DC USA. [Bossarte, Robert M.] Univ Rochester, Dept Psychiat, Rochester, NY USA. RP Blosnich, JR (reprint author), VA Pittsburgh Healthcare Syst, US Dept Vet Affairs, Ctr Hlth Equ Res & Promot, Univ Dr C 151C U,Bldg 30, Pittsburgh, PA 15240 USA. EM john.blosnich@va.gov FU VA Health Service Research Development [CDA 14-408] FX This work was supported by a career development award to [name masked for review] from VA Health Service Research & Development (CDA 14-408). The opinions expressed in this work are those of the authors and do not necessarily represent those of the funders, institutions, the Department of Veterans Affairs, or the U.S. Government. NR 24 TC 0 Z9 0 U1 6 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 EI 1873-2585 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD AUG PY 2016 VL 26 IS 8 BP 592 EP 596 DI 10.1016/j.annepidem.2016.06.009 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DU3HU UT WOS:000382102200010 PM 27448820 ER PT J AU Chatelle, C Bodien, YG Carlowicz, C Wannez, S Charland-Verville, V Gosseries, O Laureys, S Seel, RT Giacino, JT AF Chatelle, Camille Bodien, Yelena G. Carlowicz, Cecilia Wannez, Sarah Charland-Verville, Vanessa Gosseries, Olivia Laureys, Steven Seel, Ron T. Giacino, Joseph T. TI Detection and Interpretation of Impossible and Improbable Coma Recovery Scale-Revised Scores SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Brain injuries; Consciousness disorders; Outcome assessment (health care); Rehabilitation ID MINIMALLY CONSCIOUS STATE; VEGETATIVE STATE; LEVEL AB Objective: To determine the frequency with which specific Coma Recovery Scale-Revised (CRS-R) subscale scores co-occur as a means of providing clinicians and researchers with an empirical method of assessing CRS-R data quality. Design: We retrospectively analyzed CRS-R subscale scores in hospital inpatients diagnosed with disorders of consciousness (DOCs) to identify impossible and improbable subscore combinations as a means of detecting inaccurate and unusual scores. Impossible subscore combinations were based on violations of CRS-R scoring guidelines. To determine improbable subscore combinations, we relied on the Mahalanobis distance, which detects outliers within a distribution of scores. Subscore pairs that were not observed at all in the database (ie, frequency of occurrence = 0%) were also considered improbable. Setting: Specialized DOC program and university hospital. Participants: Patients diagnosed with DOCs (N=1190; coma: n=76, vegetative state: n=464, minimally conscious state: n=586, emerged from minimally conscious state: n=64; 794 men; mean age, 43 +/- 20y; traumatic etiology: n=747; time postinjury, 162 +/- 568d). Interventions: Not applicable. Main Outcome Measure: Impossible and improbable CRS-R subscore combinations. Results: Of the 1190 CRS-R profiles analyzed, 4.7% were excluded because they met scoring criteria for impossible co-occurrence. Among the 1137 remaining profiles, 12.2% (41/336) of possible subscore combinations were classified as improbable. Conclusions: Clinicians and researchers should take steps to ensure the accuracy of CRS-R scores. To minimize the risk of diagnostic error and erroneous research findings, we have identified 9 impossible and 36 improbable CRS-R subscore combinations. The presence of any one of these subscore combinations should trigger additional data quality review. (C) 2016 by the American Congress of Rehabilitation Medicine C1 [Chatelle, Camille; Bodien, Yelena G.; Carlowicz, Cecilia; Giacino, Joseph T.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Chatelle, Camille; Bodien, Yelena G.; Carlowicz, Cecilia; Giacino, Joseph T.] Harvard Med Sch, Boston, MA USA. [Chatelle, Camille] Massachusetts Gen Hosp, Lab NeuroImaging Coma & Consciousness, 175 Cambridge St,Ste 300, Boston, MA 02114 USA. [Chatelle, Camille; Wannez, Sarah; Charland-Verville, Vanessa; Gosseries, Olivia; Laureys, Steven] Univ Hosp Liege, GIGA Res Ctr, Coma Sci Grp, Liege, Belgium. [Gosseries, Olivia] Univ Wisconsin, Dept Psychol, 1202 W Johnson St, Madison, WI 53706 USA. [Gosseries, Olivia] Univ Wisconsin, Dept Psychiat, Madison, WI 53706 USA. [Seel, Ron T.] Shepherd Ctr, Crawford Res Inst, Atlanta, GA USA. RP Chatelle, C (reprint author), Massachusetts Gen Hosp, Lab NeuroImaging Coma & Consciousness, 175 Cambridge St,Ste 300, Boston, MA 02114 USA. EM cchatelle@partners.org RI Laureys, Steven/A-3349-2011 FU National Institute on Disability, Independent Living, and Rehabilitation Research, Department of Health and Human Services, Administration for Community Living [90DP0039-01-00]; James S. McDonnell Foundation; Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Research Resources); Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [UL1 TR001102]; Harvard University and its affiliated academic health care centers; Belgian American Educational Foundation; Wallonie Bruxelles International Concerted Research Action; Belgian Funds for Scientific Research, European Commission; European Foundation for Biomedical Research FX Supported by the National Institute on Disability, Independent Living, and Rehabilitation Research, Department of Health and Human Services, Administration for Community Living (grant no. 90DP0039-01-00); The James S. McDonnell Foundation; Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health award no. UL1 TR001102); financial contributions from Harvard University and its affiliated academic health care centers; The Belgian American Educational Foundation; Wallonie Bruxelles International Concerted Research Action; Belgian Funds for Scientific Research, European Commission; and the European Foundation for Biomedical Research. NR 13 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD AUG PY 2016 VL 97 IS 8 BP 1295 EP 1300 DI 10.1016/j.apmr.2016.02.009 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA DT1LM UT WOS:000381244200011 PM 26944708 ER PT J AU Kesinger, MR Juengst, SB Bertisch, H Niemeier, JP Krellman, JW Pugh, M Kumar, RG Sperry, JL Arenth, PM Fann, JR Wagner, AK AF Kesinger, Matthew R. Juengst, Shannon B. Bertisch, Hillary Niemeier, Janet P. Krellman, Jason W. Pugh, MaryJo Kumar, Raj G. Sperry, Jason L. Arenth, Patricia M. Fann, Jesse R. Wagner, Amy K. TI Acute Trauma Factor Associations With Suicidality Across the First 5 Years After Traumatic Brain Injury SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Brain injuries; Injury Severity Score; Multiple trauma; Rehabilitation; Suicidal ideation; Suicide; attempted ID DEPLOYED MILITARY PERSONNEL; SUBSTANCE-ABUSE; RISK-FACTORS; CHRONIC PAIN; FOLLOW-UP; DEPRESSION; IDEATION; REHABILITATION; POPULATION; PREVALENCE AB Objective: To determine whether severity of head and extracranial injuries (ECI) is associated with suicidal ideation (SI) or suicide attempt (SA) after traumatic brain injury (TBI). Design: Factors associated with SI and SA were assessed in this inception cohort study using data collected 1, 2, and 5 years post-TBI from the National Trauma Data Bank and Traumatic Brain Injury Model Systems (TRIMS) databases. Setting: Level I trauma centers, inpatient rehabilitation centers, and the community. Participants: Participants with TBI from 15 TBIMS Centers with linked National Trauma Data Bank trauma data (N=3575). Interventions: Not applicable. Main Outcome Measures: SI was measured via the Patient Health Questionnaire 9 (question 9). SA in the last year was assessed via interview. ECI was measured by the Injury Severity Scale (nonhead) and categorized as none, mild, moderate, or severe. Results: There were 293 (8.2%) participants who had SI without SA and 109 (3.0%) who had SA at least once in the first 5 years postinjury. Random effects logit modeling showed a higher likelihood of SI when ECI was severe (odds ratio = 2.73; 95% confidence interval, 1.55-4.82; P=.001). Drug use at time of injury was also associated with SI (odds ratio =1.69; 95% confidence interval, 1.11-2.86; P=.015). Severity of ECI was not associated with SA. Conclusions: Severe ECI carried a nearly 3-fold increase in the odds of SI after TBI, but it was not related to SA. Head injury severity and less severe ECI were not associated with SI or SA. These findings warrant additional work to identify factors associated with severe ECI that make individuals more susceptible to SI after TBI. (C) 2016 by the American Congress of Rehabilitation Medicine C1 [Kesinger, Matthew R.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Juengst, Shannon B.; Kumar, Raj G.; Arenth, Patricia M.; Wagner, Amy K.] Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, 3471 Fifth Ave, Pittsburgh, PA 15213 USA. [Bertisch, Hillary] NYU, Dept Rehabil Med, Sch Med, New York, NY USA. [Niemeier, Janet P.] Carolinas Med Ctr, Dept Phys Med & Rehabil, Charlotte, NC 28203 USA. [Niemeier, Janet P.] Univ N Carolina, Chapel Hill, NC USA. [Krellman, Jason W.] Icahn Sch Med Mt Sinai, Dept Rehabil Med, New York, NY 10029 USA. [Pugh, MaryJo] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Pugh, MaryJo] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Sperry, Jason L.] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA. [Fann, Jesse R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Wagner, Amy K.] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA USA. [Wagner, Amy K.] Univ Pittsburgh, Ctr Neurosci, Pittsburgh, PA 15260 USA. [Wagner, Amy K.] Univ Pittsburgh, Safar Ctr Resuscitat Res, Pittsburgh, PA USA. RP Juengst, SB (reprint author), Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, 3471 Fifth Ave, Pittsburgh, PA 15213 USA. EM sbj7@pitt.edu FU National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) [90DP0041]; NIDILRR [90DP0038, 90DP0047]; National Institutes of Health [NIH K23GM093032]; National Institute of Mental Health Medical Student Research Fellowship [TL1TR000005, R25 MH054318]; Rusk Advanced Rehabilitation Research Training Postdoctoral Fellowship [NIDILRR 90AR5014-01-00]; Polytrauma Rehabilitation Center Traumatic Brain Injury Model System; Department of Veterans Affairs (VA) FX Support for the collection of the original data was by the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) (grant no. 90DP0041); and the National Trauma Data Bank. Support for the content of this article was by the NIDILRR (grant nos. 90DP0038 and 90DP0047); the National Institutes of Health (grant no. NIH K23GM093032); the National Institute of Mental Health Medical Student Research Fellowship (fellowship no. TL1TR000005) administered by the University of Pittsburgh (grant no. R25 MH054318); a Rusk Advanced Rehabilitation Research Training Postdoctoral Fellowship (grant no. NIDILRR 90AR5014-01-00); and the Polytrauma Rehabilitation Center Traumatic Brain Injury Model System.; The Polytrauma Rehabilitation Center Traumatic Brain Injury Model System is a funded collaboration between the Department of Veterans Affairs (VA) and the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR). The NIDILRR is a center within the Administration for Community Living (ACL), Department of Health and Human Services (HHS). The contents of this article do not necessarily represent the policy of the VA, NIDILRR, ACL, NIH, or HHS, and endorsement of this content by the Federal Government should not be assumed. NR 52 TC 1 Z9 1 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD AUG PY 2016 VL 97 IS 8 BP 1301 EP 1308 DI 10.1016/j.apmr.2016.02.017 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA DT1LM UT WOS:000381244200012 PM 26987622 ER PT J AU Ward, RE Beauchamp, MK Latham, NK Leveille, SG Percac-Lima, S Kurlinski, L Ni, PS Goldstein, R Jette, AM Bean, JF AF Ward, Rachel E. Beauchamp, Marla K. Latham, Nancy K. Leveille, Suzanne G. Percac-Lima, Sanja Kurlinski, Laura Ni, Pengsheng Goldstein, Richard Jette, Alan M. Bean, Jonathan F. TI Neuromuscular Impairments Contributing to Persistently Poor and Declining Lower-Extremity Mobility Among Older Adults: New Findings Informing Geriatric Rehabilitation SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT Meeting of the Gerontological-Society-of-America CY NOV 08, 2014 CL Washington, DC SP Gerontol Soc Amer DE Aged; Mobility limitation; Muscle strength; Range of motion; articular; Rehabilitation ID GONIOMETRIC MEASUREMENTS; RISK-ASSESSMENT; LIMITED ELDERS; PERFORMANCE; DISABILITY; WOMEN; KYPHOSIS; BALANCE; RELIABILITY; ATTRIBUTES AB Objective: To identify neuromuscular impairments most predictive of unfavorable mobility outcomes in late life. Design: Longitudinal cohort study. Setting: Research clinic. Participants: Community-dwelling primary care patients aged >= 65 years (N=391) with self-reported mobility modifications, randomly selected from a research registry. Interventions: Not applicable. Main Outcome Measures: Categories of decline in and persistently poor mobility across baseline, 1 and 2 years of follow-up in the Lower-Extremity Function scales of the Late-Life Function and Disability Instrument. The following categories of impairment were assessed as potential predictors of mobility change: strength (leg strength), speed of movement (leg velocity, reaction time, rapid leg coordination), range of motion (ROM) (knee flexion/knee extension/ankle ROM), asymmetry (asymmetry of leg strength and knee flexion/extension ROM measures), and trunk stability (trunk extensor endurance, kyphosis). Results: The largest effect sizes were found for baseline weaker leg strength (odds ratio [95% confidence interval]: 3.45 [1.72-6.95]), trunk extensor endurance (2.98 [1.56-5.70]), and slower leg velocity (2.35 [1.21-4.58]) predicting a greater likelihood of persistently poor function over 2 years. Baseline weaker leg strength, trunk extensor endurance, and restricted knee flexion motion also predicted a greater likelihood of decline in function (1.72 [1.10-2.70], 1.83 [1.13-2.95], and 2.03 [1.24-3.35], respectively). Conclusions: Older adults exhibiting poor mobility may be prime candidates for rehabilitation focused on improving these impairments. These findings lay the groundwork for developing interventions aimed at optimizing rehabilitative care and disability prevention, and highlight the importance of both well-recognized (leg strength) and novel impairments (leg velocity, trunk extensor muscle endurance). (C) 2016 by the American Congress of Rehabilitation Medicine C1 [Ward, Rachel E.; Bean, Jonathan F.] Boston Vet Affairs Healthcare Syst, New England Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Ward, Rachel E.; Leveille, Suzanne G.; Percac-Lima, Sanja; Kurlinski, Laura; Goldstein, Richard; Bean, Jonathan F.] Harvard Med Sch, Boston, MA USA. [Ward, Rachel E.; Kurlinski, Laura; Goldstein, Richard; Bean, Jonathan F.] Spaulding Rehabil Hosp, 1575 Cambridge St, Cambridge, MA 02138 USA. [Beauchamp, Marla K.] McMaster Univ, Sch Rehabil Sci, Hamilton, ON, Canada. [Latham, Nancy K.; Ni, Pengsheng; Jette, Alan M.] Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, Boston, MA USA. [Leveille, Suzanne G.] Univ Massachusetts, Coll Nursing & Hlth Sci, Boston, MA 02125 USA. [Percac-Lima, Sanja] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ward, RE (reprint author), Spaulding Rehabil Hosp, 1575 Cambridge St, Cambridge, MA 02138 USA. EM reward@partners.org RI Bean, Jonathan/F-5798-2017 OI Bean, Jonathan/0000-0001-8385-8210 FU NCRR NIH HHS [UL1 RR025758]; NIA NIH HHS [R01 AG032052]; NICHD NIH HHS [K24 HD070966] NR 41 TC 0 Z9 0 U1 3 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD AUG PY 2016 VL 97 IS 8 BP 1316 EP 1322 DI 10.1016/j.apmr.2016.03.003 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA DT1LM UT WOS:000381244200014 PM 27056644 ER PT J AU Goverman, J Mathews, K Nadler, D Henderson, E McMullen, K Herndon, D Meyer, W Fauerbach, JA Wiechman, S Carrougher, G Ryan, CM Schneider, JC AF Goverman, J. Mathews, K. Nadler, D. Henderson, E. McMullen, K. Herndon, D. Meyer, W., III Fauerbach, J. A. Wiechman, S. Carrougher, G. Ryan, C. M. Schneider, J. C. TI Satisfaction with life after burn: A Burn Model System National Database Study SO BURNS LA English DT Article DE Burn; Satisfaction with life; Outcome ID QUALITY-OF-LIFE; STRESS-DISORDER; INJURY; HEALTH; PREDICTORS; DEPRESSION; SYMPTOMS; INTEGRATION; VALIDATION; EXPERIENCE AB Objectives: While mortality rates after burn are low, physical and psychosocial impairments are common. Clinical research is focusing on reducing morbidity and optimizing quality of life. This study examines self-reported Satisfaction With Life Scale scores in a longitudinal, multicenter cohort of survivors of major burns. Risk factors associated with Satisfaction With Life Scale scores are identified. Methods: Data from the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) Burn Model System (BMS) database for burn survivors greater than 9 years of age, from 1994 to 2014, were analyzed. Demographic and medical data were collected on each subject. The primary outcome measures were the individual items and total Satisfaction With Life Scale (SWLS) scores at time of hospital discharge (pre-burn recall period) and 6, 12, and 24 months after burn. The SWLS is a validated 5-item instrument with items rated on a 1-7 Likert scale. The differences in scores over time were determined and scores for burn survivors were also compared to a non-burn, healthy population. Step-wise regression analysis was performed to determine predictors of SWLS scores at different time intervals. Results: The SWLS was completed at time of discharge (1129 patients), 6 months after burn (1231 patients), 12 months after burn (1123 patients), and 24 months after burn (959 patients). There were no statistically significant differences between these groups in terms of medical or injury demographics. The majority of the population was Caucasian (62.9%) and male (72.6%), with a mean TBSA burned of 22.3%. Mean total SWLS scores for burn survivors were unchanged and significantly below that of a non-burn population at all examined time points after burn. Although the mean SWLS score was unchanged over time, a large number of subjects demonstrated improvement or decrement of at least one SWLS category. Gender, TBSA burned, LOS, and school status were associated with SWLS scores at 6 months; scores at 12 months were associated with LOS, school status, and amputation; scores at 24 months were associated with LOS, school status, and drug abuse. Conclusions: In this large, longitudinal, multicenter cohort of burn survivors, satisfaction with life after burn was consistently lower than that of non-burn norms. Furthermore mean SWLS scores did not improve over the two-year follow-up period. This study demonstrates the need for continued efforts to improve patient-centered long term satisfaction with life after burn. (C) 2016 Elsevier Ltd and ISBI. All rights reserved. C1 [Goverman, J.; Mathews, K.; Henderson, E.; Ryan, C. M.; Schneider, J. C.] Harvard Med Sch, Massachusetts Gen Hosp, Surg Serv, Sumner Redstone Burn Ctr, Boston, MA USA. [Goverman, J.; Mathews, K.; Nadler, D.; Ryan, C. M.; Schneider, J. C.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Goverman, J.; Ryan, C. M.; Schneider, J. C.] Shriners Hosp Children Boston, Boston, MA USA. [McMullen, K.] Univ Washington, Seattle, WA USA. [Herndon, D.; Meyer, W., III] Shriners Hosp Children Galveston, Galveston, TX USA. [Herndon, D.; Meyer, W., III] Univ Texas Med Branch, Dept Surg, Galveston, TX 77555 USA. [Meyer, W., III] Univ Texas Med Branch, Sch Med, Dept Psychiat & Behav Sci, Galveston, TX 77555 USA. [Fauerbach, J. A.] Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA. [Wiechman, S.] Univ Washington, Burn Ctr, Harborview Med Ctr, Dept Rehabil Med,Psychol, Seattle, WA 98195 USA. [Carrougher, G.] Univ Washington, Dept Surg, Seattle, WA 98195 USA. [Wiechman, S.] Harborview Med Ctr, Seattle, WA USA. RP Schneider, JC (reprint author), Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. EM jcschneider@partners.org FU National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) [90DP0035] FX The contents of this manuscript were developed under a grant from the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR grant number 90DP0035). NIDILRR is a Center within the Administration for Community Living (ACL), Department of Health and Human Services (HHS). The contents of this manuscript do not necessarily represent the policy of NIDILRR, ACL, HHS, and you should not assume endorsement by the Federal Government. NR 30 TC 0 Z9 0 U1 9 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-4179 EI 1879-1409 J9 BURNS JI Burns PD AUG PY 2016 VL 42 IS 5 BP 1067 EP 1073 DI 10.1016/j.bunis.2016.01.018 PG 7 WC Critical Care Medicine; Dermatology; Surgery SC General & Internal Medicine; Dermatology; Surgery GA DU7SD UT WOS:000382414000008 PM 27215148 ER PT J AU Ryan, CM Cartwright, S Schneider, JC Tompkins, RG Kazis, LE AF Ryan, Colleen M. Cartwright, Sara Schneider, Jeffrey C. Tompkins, Ronald G. Kazis, Lewis E. TI The burn outcome questionnaires: Patient and family reported outcome metrics for children of all ages SO BURNS LA English DT Letter ID QUALITY-OF-LIFE; ASSOCIATION/SHRINERS-HOSPITALS; HEALTH OUTCOMES; YOUNG-ADULTS; RECOVERY; INJURY; VALIDATION C1 [Ryan, Colleen M.; Schneider, Jeffrey C.; Tompkins, Ronald G.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02115 USA. [Ryan, Colleen M.; Schneider, Jeffrey C.] Shriners Hosp Children, Boston, MA USA. [Ryan, Colleen M.; Cartwright, Sara; Schneider, Jeffrey C.] Harvard Med Sch, Spaulding Rehabil Hosp, Boston, MA USA. [Kazis, Lewis E.] Boston Univ, Dept Hlth Policy & Management, Sch Publ Hlth, Ctr Assessment Pharmaceut Practices, Boston, MA USA. RP Ryan, CM (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02115 USA. EM cryan@partners.org OI Ryan, Colleen/0000-0002-6455-936X NR 17 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 0305-4179 EI 1879-1409 J9 BURNS JI Burns PD AUG PY 2016 VL 42 IS 5 BP 1144 EP 1145 DI 10.1016/j.burns.2015.10.033 PG 2 WC Critical Care Medicine; Dermatology; Surgery SC General & Internal Medicine; Dermatology; Surgery GA DU7SD UT WOS:000382414000023 PM 26803370 ER PT J AU Nishimura, K Shindo, S Movila, A Kayal, R Abdullah, A Savitri, IJ Ikeda, A Yamaguchi, T Howait, M Al-Dharrab, A Mira, A Han, XZ Kawai, T AF Nishimura, Kazuaki Shindo, Satoru Movila, Alexandru Kayal, Rayyan Abdullah, Albassam Savitri, Irma Josefina Ikeda, Atsushi Yamaguchi, Tsuguno Howait, Mohammed Al-Dharrab, Ayman Mira, Abdulghani Han, Xiaozhe Kawai, Toshihisa TI TRAP-positive osteoclast precursors mediate ROS/NO-dependent bactericidal activity via TLR4 SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Osteoclast; Bacteria; Phagocytosis; Toll-like receptor; Tartrate-resistant acid phosphatase; Reactive oxygen species; Nitric oxide; RANKL ID TOLL-LIKE RECEPTORS; COLONY-STIMULATING FACTOR; IN-VITRO; BONE-RESORPTION; INNATE IMMUNITY; INTERFERON-BETA; RANK LIGAND; DIFFERENTIATION; INHIBITION; PERIODONTITIS AB Osteoclastogenesis was induced by RANKL stimulation in mouse monocytes to examine the possible bactericidal function of osteoclast precursors (OCp) and mature osteoclasts (OCm) relative to their production of NO and ROS. Tartrate-resistant acid phosphatase (TRAP)-positive OCp, but few or no OCm, phagocytized and killed Escherichia coil in association with the production of reactive oxygen species (ROS) and nitric oxide (NO). Phagocytosis of E. coll. and production of ROS and NO were significantly lower in TRAP+ OCp derived from Toll-like receptor (TLR)-4 KO mice than that derived from wild-type (WT) or TLR2-KO mice. Interestingly, after phagocytosis, TRAP+ OCp derived from wild-type and TLR2KO mice did not differentiate into OCm, even with continuous exposure to RANKL. In contrast, E. coll.phagocytized TRAP+ OCp from TLR4-KO mice could differentiate into OCm. Importantly, neither NO nor ROS produced by TRAP+ OCp appeared to be engaged in phagocytosis-induced suppression of osteoclastogenesis. These results suggested that TLR4 signaling not only induces ROS and NO production to kill phagocytized bacteria, but also interrupts OCm differentiation. Thus, it can be concluded that TRAP+ OCp, but not OCm, can mediate bactericidal activity via phagocytosis accompanied by the production of ROS and NO via TLR4-associated reprograming toward phagocytic cell type. (C) 2016 Elsevier Inc. All rights reserved. C1 [Nishimura, Kazuaki; Shindo, Satoru; Movila, Alexandru; Abdullah, Albassam; Ikeda, Atsushi; Yamaguchi, Tsuguno; Han, Xiaozhe; Kawai, Toshihisa] Forsyth Inst, Dept Immunol & Infect Dis, 245 First St, Cambridge, MA 02142 USA. [Nishimura, Kazuaki] Tohoku Univ Hosp, Maxillooral Disorders, Sendai, Miyagi, Japan. [Shindo, Satoru] Univ Tokushima, Inst Hlth Biosci, Dept Conservat Dent, Grad Sch, Tokushima, Japan. [Kayal, Rayyan; Abdullah, Albassam; Howait, Mohammed; Al-Dharrab, Ayman; Mira, Abdulghani] King Abdulaziz Univ, Fac Dent, Jeddah, Saudi Arabia. [Savitri, Irma Josefina] Airlangga Univ, Dept Periodont, Jawa Timur, Indonesia. [Yamaguchi, Tsuguno] LION Corp, Res & Dev Headquarters, 100 Tajima Odawara, Odawara, Kanagawa, Japan. [Han, Xiaozhe; Kawai, Toshihisa] Harvard Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA USA. RP Kawai, T (reprint author), Forsyth Inst, Dept Immunol & Infect Dis, 245 First St, Cambridge, MA 02142 USA. EM knishimura@dent.tohoku.ac.jp; c301351004@tokushima-u.ac.jp; amovila@forsyth.org; rkayal@kau.edu.sa; albassam.a@hotmail.com; irmaudijanto@gmail.com; aikeda@forsyth.org; tsuguno@gmail.com; mhowait@icloud.com; aaldharab@kau.edu.sa; amira@kau.edu.sa; XHan@forsyth.org; tkawai@forsyth.org RI Howait, Mohammed/K-4478-2016 OI Howait, Mohammed/0000-0002-6268-4941 FU NIH [RO1 DE-018499, RO1 DE-019917, R56 DE023807, R01DE025255]; National Institute of Dental and Craniofacial Research (NIDCR) [T32 DE 7327-12]; King Abdulaziz University (KAU) FX This work was partially supported by NIH grants RO1 DE-018499, RO1 DE-019917, R56 DE023807 and R01DE025255 and T32 DE 7327-12 from National Institute of Dental and Craniofacial Research (NIDCR) and a research fund from King Abdulaziz University (KAU). NR 62 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 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD AUG PY 2016 VL 97 BP 330 EP 341 DI 10.1016/j.freeradbiomed.2016.06.021 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA DU0VZ UT WOS:000381924100030 PM 27343691 ER PT J AU Wu, N Wang, Y Yang, LB Cho, KS AF Wu, Nan Wang, Yi Yang, Lanbo Cho, Kin-Sang TI Signaling Networks of Retinal Ganglion Cell Formation and the Potential Application of Stem Cell-Based Therapy in Retinal Degenerative Diseases SO HUMAN GENE THERAPY LA English DT Article ID NEURAL PROGENITOR CELLS; DEVELOPING MOUSE RETINA; ROD PHOTORECEPTOR DEVELOPMENT; IN-VITRO DIFFERENTIATION; TRANSCRIPTION FACTOR NRL; DOMAIN FACTOR BRN-3B; LEUCINE-ZIPPER NRL; CRX-DEFICIENT MICE; VERTEBRATE RETINA; SONIC HEDGEHOG AB Retinal degenerative diseases such as age-related macular degeneration, retinitis pigmentosa, and glaucoma result in permanent loss of retinal neurons and vision. Stem cell therapy could be a novel treatment strategy to restore visual function. In an ideal situation, a homogenous population of stem cell-derived retinal neurons with high purity is used for replacement therapy. Thus, it is crucial to elucidate the molecular mechanisms that regulate the development of retinal progenitor cells and subsequent generation of specific retinal neurons. Here, recent findings concerning the intrinsic and extrinsic factors that regulate retinal progenitor cell maintenance and differentiation are summarized, especially transcriptional factors and extrinsic signals. Understanding these mechanisms is indispensable because they have potential clinical applications, chiefly the generation of specific retinal cells such as retinal ganglion cells to treat glaucoma and other optic neuropathy diseases. C1 [Wu, Nan; Wang, Yi] Third Mil Med Univ, Southwest Hosp, Southwest Eye Hosp, Dept Ophthalmol, Chongqing, Peoples R China. [Yang, Lanbo; Cho, Kin-Sang] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA USA. RP Cho, KS (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM kinsang_cho@meei.harvard.edu FU National Natural Science Foundation of China [30901645]; Youth Innovation Fund of the Third Military Medical University [2009XQN29] FX The study was supported by grants from National Natural Science Foundation of China (grant no. 30901645) and the Youth Innovation Fund of the Third Military Medical University (grant no. 2009XQN29). NR 150 TC 0 Z9 0 U1 2 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD AUG PY 2016 VL 27 IS 8 BP 609 EP 620 DI 10.1089/hum.2016.083 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA DU6AQ UT WOS:000382295500005 PM 27466076 ER EF