FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Eaton, BR Chowdhry, V Weaver, K Liu, L Ebb, D MacDonald, SM Tarbell, NJ Yock, TI AF Eaton, Bree R. Chowdhry, Varun Weaver, Kenneth Liu, Li Ebb, David MacDonald, Shannon M. Tarbell, Nancy J. Yock, Torunn I. TI Use of proton therapy for re-irradiation in pediatric intracranial ependymoma SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Proton; Re-irradiation; Radiotherapy; Pediatric; Ependymoma ID RECURRENT EPENDYMOMA; STEREOTACTIC RADIOSURGERY; CHILDHOOD EPENDYMOMA; CLINICAL-OUTCOMES; RADIATION-THERAPY; CHILDREN; RADIOTHERAPY; SURVIVAL; PATTERNS AB Background and purpose: To report disease control, survival and treatment-associated toxicity with the use of proton therapy (PAT) for re-irradiation of intracranial ependymoma. Materials and methods: Twenty patients underwent 33 PRT re-irradiation courses for recurrent or metastatic lesions between June 2004 and February 2015 at Massachusetts General Hospital. Results: The majority of patients were female (60%), with infratentorial tumors (90%), anaplastic histology (55%), and initially received 55.8 GyRBE (52.2-59.4) involved field (IF) PRT. First failure was local (55%), distant (30%) or both (15%) at a median time of 23.9 months (9.9-98.5) from first treatment. Salvage therapy included re-resection (75%), chemotherapy (60%) and IFPRT (70%) to a median dose 50.4 GyRBE (35-55.8) in the majority of patients. The median follow-up was 37.8 months (5.5-138.0). Three year OS and PFS are 78.6% (95% CI 67.6-89.6) and 28.1% (95% CI 15.6-40.6), respectively. Longer OS was significantly associated with surgical resection of recurrent disease (HR 9.19, 95% CI 1.27-66.44, p = 0.028). The pattern of second failure after re-irradiation was directly related to the pattern of first failure (p < 0.01). Three of 14 patients (21.4%) locally re-treated experienced grade 2 radiation-associated treatment change. Conclusions: Proton therapy appears safe and efficacious for the re-treatment of recurrent intracranial ependymoma. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Eaton, Bree R.; Chowdhry, Varun; Weaver, Kenneth; Liu, Li; MacDonald, Shannon M.; Tarbell, Nancy J.; Yock, Torunn I.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Ebb, David] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Yock, TI (reprint author), Massachusetts Gen Hosp, Proton Ctr, 55 Fruit St,Room 110, Boston, MA 02114 USA. EM tyock@partners.org NR 20 TC 3 Z9 3 U1 0 U2 1 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 2015 VL 116 IS 2 BP 301 EP 308 DI 10.1016/j.radonc.2015.07.023 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CT8PE UT WOS:000363077700024 PM 26243681 ER PT J AU Chan, BT Tsai, AC Siedner, MJ AF Chan, Brian T. Tsai, Alexander C. Siedner, Mark J. TI HIV Treatment Scale-Up and HIV-Related Stigma in Sub-Saharan Africa: A Longitudinal Cross-Country Analysis SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID CLUSTER-RANDOMIZED TRIAL; AIDS-RELATED STIGMA; ANTIRETROVIRAL THERAPY; RURAL UGANDA; SOUTH-AFRICA; INTERNALIZED STIGMA; CAPE-TOWN; HIV/AIDS; PEOPLE; TRANSMISSION AB Objectives. We estimated the association between antiretroviral therapy (ART) uptake and HIV-related stigma at the population level in sub-Saharan Africa. Methods. We examined trends in HIV-related stigma and ART coverage in sub-Saharan Africa during 2003 to 2013 using longitudinal, population-based data on ART coverage from the Joint United Nations Program on HIV/AIDS and on HIV-related stigma from the Demographic and Health Surveys and AIDS Indicator Surveys. We fitted 2 linear regression models with country fixed effects, with the percentage of men or women reporting HIV-related stigma as the dependent variable and the percentage of people living with HIV on ART as the explanatory variable. Results. Eighteen countries in sub-Saharan Africa were included in our analysis. For each 1% increase in ART coverage, we observed a statistically significant decrease in the percentage of women (b = -0.226; P = .007; 95% confidence interval [CI] = -0.383, -0.070) and men (b = -0.281; P = .009; 95% CI = -0.480, -0.082) in the general population reporting HIV-related stigma. Conclusions. An important benefit of ART scale-up may be the diminution of HIV-related stigma in the general population. C1 [Chan, Brian T.; Tsai, Alexander C.; Siedner, Mark J.] Harvard Univ, Sch Med, Boston, MA USA. [Chan, Brian T.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Tsai, Alexander C.; Siedner, Mark J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Chan, BT (reprint author), Brigham & Womens Hosp, 15 Francis St,PBBA 4, Boston, MA 02115 USA. EM bchan@partners.org OI Tsai, Alexander/0000-0001-6397-7917 FU National Institutes of Health [T32AI007433, K23MH096620, K23MH099916]; David Brudnoy Scholar Award; 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) [KL2 TR001100] FX We acknowledge the following additional sources of support: the National Institutes of Health (T32AI007433 [B. T. C.], K23MH096620 [A. C. T.], K23MH099916 [Siedner]), David Brudnoy Scholar Award (B. T. C.), and Harvard Catalyst 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 KL2 TR001100, an appointed KL2/Catalyst Medical Research Investigator Training award to B. T. C.). NR 60 TC 7 Z9 7 U1 2 U2 8 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 2015 VL 105 IS 8 BP 1581 EP 1587 DI 10.2105/AJPH.2015.302716 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CT6VL UT WOS:000362950400043 PM 26066939 ER PT J AU Dismuke, CE Gebregziabher, M Yeager, D Egede, LE AF Dismuke, Clara E. Gebregziabher, Mulugeta Yeager, Derik Egede, Leonard E. TI Racial/Ethnic Differences in Combat- and Non-Combat-Associated Traumatic Brain Injury Severity in the Veterans Health Administration: 2004-2010 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID FUNCTIONAL OUTCOMES; ETHNIC DISPARITIES; MILITARY PERSONNEL; REHABILITATION; SERVICE; IRAQ; DISORDERS; RISK AB Objectives. We examined the association between traumatic brain injury (TBI) severity and combat exposure by race/ethnicity. Methods. We estimated logit models of the fully adjusted association of combat exposure with TBI severity in separate race/ethnicity models for a national cohort of 132 995 veterans with TBI between 2004 and 2010. Results. Of veterans with TBI, 25.8% had served in a combat zone. Mild TBI increased from 11.5% to 40.3%, whereas moderate or severe TBI decreased from 88.5% to 59.7%. Moderate or severe TBI was higher in non-Hispanic Blacks (80.0%) and Hispanics (89.4%) than in non-Hispanic Whites (71.9%). In the fully adjusted all-race/ethnicity model, non-Hispanic Blacks (1.44; 95% confidence interval [CI] = 1.37, 1.52) and Hispanics (1.47; 95% CI = 1.26, 1.72) had higher odds of moderate or severe TBI than did non-Hispanic Whites. However, combat exposure was associated with higher odds of mild TBI in non-Hispanic Blacks (2.48; 95% CI = 2.22, 2.76) and Hispanics (3.42; 95% CI = 1.84, 6.35) than in non-Hispanic Whites (2.17; 95% CI = 2.09, 2.26). Conclusions. Research is needed to understand racial differences in the effect of combat exposure on mild TBI and on interventions to prevent TBI across severity levels. C1 [Dismuke, Clara E.; Gebregziabher, Mulugeta; Yeager, Derik; Egede, Leonard E.] Ralph H Johnson Vet Affairs Med Ctr, Hlth Equ & Rural Outreach Innovat Ctr, Charleston, SC USA. [Dismuke, Clara E.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Dismuke, Clara E.; Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. [Gebregziabher, Mulugeta] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280H,POB 250593, Charleston, SC 29425 USA. EM egedel@musc.edu OI Gebregziabher, Mulugeta/0000-0002-4826-481X NR 27 TC 1 Z9 1 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD AUG PY 2015 VL 105 IS 8 BP 1696 EP 1702 DI 10.2105/AJPH.2014.302545 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CT6VL UT WOS:000362950400059 PM 26066928 ER PT J AU Simonetti, JA Rowhani-Rahbar, A Mills, B Young, B Rivara, FP AF Simonetti, Joseph A. Rowhani-Rahbar, Ali Mills, Brianna Young, Bessie Rivara, Frederick P. TI State Firearm Legislation and Nonfatal Firearm Injuries SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID NATIONAL INPATIENT SAMPLE; ACCESS PREVENTION LAWS; TERM MARKED DEFICITS; QUALITY-OF-LIFE; UNITED-STATES; ADOLESCENT CHILDREN; MEDICAL COSTS; DEATH RATES; GUN LAWS; SUICIDE AB Objectives. We investigated whether stricter state-level firearm legislation was associated with lower hospital discharge rates for nonfatal firearm injuries. Methods. We estimated discharge rates for hospitalized and emergency department-treated nonfatal firearm injuries in 18 states in 2010 and used negative binomial regression to determine whether strength of state firearm legislation was independently associated with total nonfatal firearm injury discharge rates. Results. We identified 26 744 discharges for nonfatal firearm injuries. The overall age-adjusted discharge rate was 19.0 per 100 000 person-years (state range = 3.3-36.6), including 7.9 and 11.1 discharges per 100 000 for hospitalized and emergency department-treated injuries, respectively. In models adjusting for differences in state sociodemographic characteristics and economic conditions, states in the strictest tertile of legislative strength had lower discharge rates for total (incidence rate ratio [IRR] = 0.60; 95% confidence interval [CI] = 0.44, 0.82), assault-related (IRR = 0.58; 95% CI = 0.34, 0.99), self-inflicted (IRR = 0.18; 95% CI = 0.14, 0.24), and unintentional (IRR = 0.53; 95% CI = 0.34, 0.84) nonfatal firearm injuries. Conclusions. There is significant variation in state-level hospital discharge rates for nonfatal firearm injuries, and stricter state firearm legislation is associated with lower discharge rates for such injuries. C1 [Simonetti, Joseph A.; Rowhani-Rahbar, Ali; Mills, Brianna; Rivara, Frederick P.] Univ Washington, Harborview Injury Prevent & Res Ctr, Seattle, WA USA. [Simonetti, Joseph A.; Young, Bessie] VA Puget Sound Healthcare Syst, Seattle Denver Ctr Innovat, Seattle, WA 98101 USA. [Rowhani-Rahbar, Ali; Mills, Brianna] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Young, Bessie] Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA. [Rivara, Frederick P.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. RP Simonetti, JA (reprint author), VA Puget Sound Healthcare Syst, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM simonja@uw.edu FU Ruth L. Kirschstein National Research Service [T32HP10002]; Veterans Affairs Puget Sound Healthcare System, University of Washington; Harborview Injury Prevention and Research Center; Health Resources and Services Administration (HRSA) FX This study was supported by the Ruth L. Kirschstein National Research Service (award (T32HP10002 to J. A. S.); the Veterans Affairs Puget Sound Healthcare System, University of Washington; the Harborview Injury Prevention and Research Center; and the Health Resources and Services Administration (HRSA). NR 64 TC 3 Z9 3 U1 1 U2 7 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 2015 VL 105 IS 8 BP 1703 EP 1709 DI 10.2105/AJPH.2015.302617 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CT6VL UT WOS:000362950400060 PM 26066935 ER PT J AU Miyake, M Yamashiro, K Tamura, H Kumagai, K Saito, M Sugahara-Kuroda, M Yoshikawa, M Oishi, M Akagi-Kurashige, Y Nakata, I Nakanishi, H Gotoh, N Oishi, A Matsuda, F Yamada, R Khor, CC Kurimoto, Y Sekiryu, T Tsujikawa, A Yoshimura, N AF Miyake, Masahiro Yamashiro, Kenji Tamura, Hiroshi Kumagai, Kyoko Saito, Masaaki Sugahara-Kuroda, Masako Yoshikawa, Munemitsu Oishi, Maho Akagi-Kurashige, Yumiko Nakata, Isao Nakanishi, Hideo Gotoh, Norimoto Oishi, Akio Matsuda, Fumihiko Yamada, Ryo Khor, Chiea-Chuen Kurimoto, Yasuo Sekiryu, Tetsuju Tsujikawa, Akitaka Yoshimura, Nagahisa TI The Contribution of Genetic Architecture to the 10-Year Incidence of Age-Related Macular Degeneration in the Fellow Eye SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE age-related macular degeneration; genetics; second-eye involvement; bilateral AMD ID COMPLEMENT FACTOR-H; POLYPOIDAL CHOROIDAL VASCULOPATHY; GENOME-WIDE ASSOCIATION; RISK-FACTORS; JAPANESE POPULATION; SUSCEPTIBILITY; POLYMORPHISM; VARIANTS; PREVALENCE; LOCI AB PURPOSE. To correlate a genetic risk score based on age-related macular degeneration (AMD) susceptibility genes with the risk of AMD in the second eye. METHODS. This is a retrospective, open cohort study consisting of 891 unilateral AMD patients, who were followed for at least 12 months and recruited from three institutes. DNAs were genotyped using Illumina OmniExpress, HumanOmni2.5-8, and/or HumanExome. Survival analyses and Cox proportional hazard models were used to examine the association between 11 AMD susceptibility genes and the duration until second-eye involvement in 499 samples from Kyoto University, which were replicated in two other cohorts. Genetic risk score (GRS) was also evaluated. RESULTS. The ARMS2 rs10490924 recessive model (hazard ratio [HR](meta) = 2.04; P-meta = 3.4 x 10(-3)) and CFH rs800292 additive model (HRmeta = 1.77; P-meta = 0.013) revealed significant associations with second-eye involvement. The dominant model of TNFRSF10A rs13278062, VEGFA rs943080, and CFI rs4698775 showed consistent effects across three datasets (I-2 = 0%; HRmeta = 1.46, 1.30, 1.51, respectively). The GRS using these five single nucleotide polymorphisms (SNPs) was also significantly associated (HRmeta [per score] = 2.42; P = 2.2 x 10(-5); I-2 = 0%). After 10 years from the first visit, the patients within the top 10% by GRS showed a 51% hazard rate, in contrast to 2.3% among patients within the lowest 10% by GRS. CONCLUSIONS. We demonstrated that the GRS using ARMS2, CFH, TNFRSF10A, VEGFA, and CFI was significantly associated with second-eye involvement. Genetic risk has high predictive ability for second-eye involvement of AMD. C1 [Miyake, Masahiro; Yamashiro, Kenji; Tamura, Hiroshi; Kumagai, Kyoko; Sugahara-Kuroda, Masako; Yoshikawa, Munemitsu; Oishi, Maho; Akagi-Kurashige, Yumiko; Nakanishi, Hideo; Gotoh, Norimoto; Oishi, Akio; Yoshimura, Nagahisa] Kyoto Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Kyoto 6068507, Japan. [Miyake, Masahiro; Yoshikawa, Munemitsu; Akagi-Kurashige, Yumiko; Gotoh, Norimoto; Matsuda, Fumihiko; Yamada, Ryo] Kyoto Univ, Grad Sch Med, Ctr Genom Med, Kyoto 6068507, Japan. [Saito, Masaaki; Sekiryu, Tetsuju] Fukushima Med Univ, Dept Ophthalmol, Fukushima, Japan. [Nakata, Isao] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Oishi, Akio; Kurimoto, Yasuo] Kobe City Med Ctr Gen Hosp, Kobe, Hyogo, Japan. [Khor, Chiea-Chuen] Genome Inst Singapore, Div Human Genet, Singapore, Singapore. [Tsujikawa, Akitaka] Kagawa Univ, Dept Ophthalmol, Takamatsu, Kagawa 760, Japan. RP Yamashiro, K (reprint author), Kyoto Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Sakyo Ku, 54 Kawahara, Kyoto 6068507, Japan. EM yamashro@kuhp.kyoto-u.ac.jp OI Khor, Chiea Chuen/0000-0002-1128-4729 NR 47 TC 0 Z9 0 U1 0 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD AUG PY 2015 VL 56 IS 9 BP 5353 EP 5361 DI 10.1167/iovs.14-16020 PG 9 WC Ophthalmology SC Ophthalmology GA CT5WW UT WOS:000362882800042 PM 26275133 ER PT J AU Mattapallil, MJ Silver, PB Cortes, LM St Leger, AJ Jittayasothorn, Y Kielczewski, JL Moon, JJ Chan, CC Caspi, RR AF Mattapallil, Mary J. Silver, Phyllis B. Cortes, Lizette M. St Leger, Anthony J. Jittayasothorn, Yingyos Kielczewski, Jennifer L. Moon, James J. Chan, Chi-Chao Caspi, Rachel R. TI Characterization of a New Epitope of IRBP That Induces Moderate to Severe Uveoretinitis in Mice With H-2(b) Haplotype SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE autoimmune; EAU; IRBP; H-2(b) mice ID RETINOID-BINDING PROTEIN; AUTOREACTIVE T-CELLS; AUTOIMMUNE UVEORETINITIS; UVEITIS; IDENTIFICATION; FREQUENCY; PEPTIDES; DISEASE; CD4(+); MODEL AB PURPOSE. Experimental autoimmune uveitis (EAU) induced in mice using the retinal antigen interphotoreceptor retinoid binding protein (IRBP) is an animal model for posterior uveitis in humans. However, EAU induced by native IRBP protein or its widely used epitope amino acid residues 1 to 20 of human IRBP (hIRBP1-20) is inconsistent, often showing low scores and incidence. We found an urgent need to identify a better pathogenic epitope for the C57BL/6 strain. METHODS. Mice were immunized with uveitogenic peptides or with native bovine IRBP. Clinical and histological disease and associated immunological responses were evaluated. Truncated and substituted peptides, as well as bioinformatic analyses, were used to identify critical major histocompatibility complex (MHC)/T cell receptor (TCR) contact residues and the minimal core epitope. RESULTS. The new uveitogenic epitope of IRBP, amino acid residues 651 to 670 of human IRBP (LAQGAYRTAVDLESLASQLT [hIRBP651-670]) is uveitogenic for mice of the H-2(b) haplotype and elicits EAU with a higher severity and incidence in C57BL/6 mice than the previously characterized hIRBP1-20 epitope. Using truncated and substituted peptides, as well as bioinformatic analysis, we identified the critical contact residues with MHC/TCR and defined the minimal core epitope. This made it possible to design MHC tetramers and use them to detect epitope-specific T cells in the uveitic eye and in lymphoid organs of hIRBP651-670-immunized mice. CONCLUSIONS. Data suggest that hIRBP651-670 is an epitope naturally processed from a conserved region of native IRBP, potentially explaining its relatively high uveitogenicity. This epitope should be useful for basic and preclinical studies of uveitis in the C57BL/6 model and gives access to genetically engineered mice available on this background. C1 [Mattapallil, Mary J.; Silver, Phyllis B.; Cortes, Lizette M.; St Leger, Anthony J.; Jittayasothorn, Yingyos; Kielczewski, Jennifer L.; Chan, Chi-Chao; Caspi, Rachel R.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Moon, James J.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Moon, James J.] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA. [Moon, James J.] Harvard Univ, Sch Med, Boston, MA USA. RP Caspi, RR (reprint author), NEI, Immunol Lab, 10 Ctr Dr,10-10N222, Bethesda, MD 20892 USA. EM rcaspi@helix.nih.gov OI Caspi, Rachel/0000-0002-7140-7671 FU Intramural NIH HHS; NEI NIH HHS [ZIA EY000184]; NIAID NIH HHS [AI107020, R01 AI107020, U19 AI095261] NR 25 TC 6 Z9 6 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD AUG PY 2015 VL 56 IS 9 BP 5439 EP 5449 DI 10.1167/iovs.15-17280 PG 11 WC Ophthalmology SC Ophthalmology GA CT5WW UT WOS:000362882800053 PM 26284549 ER PT J AU Liu, XS Genet, MD Haines, JE Mehanna, EK Wu, SW Chen, HIH Chen, YD Qureshi, AA Han, JL Chen, X Fisher, DE Pandolfi, PP Yuan, ZM AF Liu, Xue-Song Genet, Matthew D. Haines, Jenna E. Mehanna, Elie K. Wu, Shaowei Chen, Hung-I Harry Chen, Yidong Qureshi, Abrar A. Han, Jiali Chen, Xiang Fisher, David E. Pandolfi, Pier Paolo Yuan, Zhi-Min TI ZBTB7A Suppresses Melanoma Metastasis by Transcriptionally Repressing MCAM SO MOLECULAR CANCER RESEARCH LA English DT Article ID FULLY HUMAN-ANTIBODIES; MALIGNANT-MELANOMA; TUMOR-GROWTH; POZ DOMAIN; CANCER; EXPRESSION; MCAM/MUC18; PROTEIN; CELLS; MOLECULE AB The excessive metastatic propensity of melanoma makes it the most deadly form of skin cancer, yet the underlying mechanism of metastasis remains elusive. Here, mining of cancer genome datasets discovered a frequent loss of chromosome 19p13.3 and associated downregulation of the zinc finger transcription factor ZBTB7A in metastatic melanoma. Functional assessment of ZBTB7A-regulated genes identified MCAM, which encodes an adhesion protein key to melanoma metastasis. Using an integrated approach, it is demonstrated that ZBTB7A directly binds to the promoter and transcriptionally represses the expression of MCAM, establishing ZBTB7A as a bona fide transcriptional repressor of MCAM. Consistently, downregulation of ZBTB7A results in marked upregulation of MCAM and enhanced melanoma cell invasion and metastasis. An inverse correlation of ZBTB7A and MCAM expression in association with melanoma metastasis is further validated with data from analysis of human melanoma specimens. C1 [Liu, Xue-Song; Genet, Matthew D.; Haines, Jenna E.; Mehanna, Elie K.; Yuan, Zhi-Min] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. [Wu, Shaowei; Han, Jiali] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Chen, Hung-I Harry; Chen, Yidong] Univ Texas San Antonio, Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX USA. [Qureshi, Abrar A.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Chen, Xiang] Cent S Univ, Xiangya Hosp, Changsha, Hunan, Peoples R China. [Fisher, David E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02115 USA. [Pandolfi, Pier Paolo] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr,Dept Med, Canc Genet Program,Beth Israel Deaconess Canc Ctr, Boston, MA 02115 USA. [Pandolfi, Pier Paolo] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. RP Yuan, ZM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, 665 Huntington Ave, Boston, MA 02115 USA. EM zyuan@hsph.harvard.edu FU Morningside Foundation; NIH/NCI [R01CA085679, RO1CA167814, RO1CA125144] FX This work was supported in part by the Morningside Foundation and grants from the NIH/NCI (R01CA085679, RO1CA167814, and RO1CA125144). NR 30 TC 0 Z9 0 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD AUG PY 2015 VL 13 IS 8 BP 1206 EP 1217 DI 10.1158/1541-7786.MCR-15-0169 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CT7JP UT WOS:000362991300005 PM 25995384 ER PT J AU Deng, B Fradkin, M Rouet, JM Moore, RH Kopans, DB Boas, DA Lundqvist, M Fang, QQ AF Deng, Bin Fradkin, Maxim Rouet, Jean-Michel Moore, Richard H. Kopans, Daniel B. Boas, David A. Lundqvist, Mats Fang, Qianqian TI Characterizing breast lesions through robust multimodal data fusion using independent diffuse optical and x-ray breast imaging SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE diffuse optical imaging; mammography; multimodality; image reconstruction ID NEOADJUVANT CHEMOTHERAPY; TOMOGRAPHY; MAMMOGRAPHY; SPECTROSCOPY; ALGORITHM; CANCER; MRI AB To enable tissue function-based tumor diagnosis over the large number of existing digitalmammography systems worldwide, we propose a cost-effective and robust approach to incorporate tomographic optical tissue characterization with separately acquired digital mammograms. Using a flexible contour-based registration algorithm, we were able to incorporate an independently measured two-dimensional x-ray mammogram as structural priors in a joint optical/x-ray image reconstruction, resulting in improved spatial details in the optical images and robust optical property estimation. We validated this approach with a retrospective clinical study of 67 patients, including 30 malignant and 37 benign cases, and demonstrated that the proposed approach can help to distinguish malignant from solid benign lesions and fibroglandular tissues, with a performance comparable to the approach using spatially coregistered optical/ x-ray measurements. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. C1 [Deng, Bin; Boas, David A.; Fang, Qianqian] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Fradkin, Maxim; Rouet, Jean-Michel] Philips Res Medisys, F-92156 Suresnes, France. [Moore, Richard H.; Kopans, Daniel B.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Lundqvist, Mats] Philips Healthcare, S-17141 Solna, Sweden. RP Fang, QQ (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM fangq@nmr.mgh.harvard.edu FU Massachusetts Life Sciences Center; Massachusetts General Hospital Executive Committee on Research Interim Support Funding; NIH [R01-CA97305, R01-CA142575, 1S10RR023043] FX The authors acknowledge the Cooperative Research Matching Grant from the Massachusetts Life Sciences Center, Massachusetts General Hospital Executive Committee on Research Interim Support Funding, and the NIH funding support under grants R01-CA97305, R01-CA142575, and 1S10RR023043. NR 13 TC 1 Z9 1 U1 4 U2 10 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD AUG PY 2015 VL 20 IS 8 AR 080502 DI 10.1117/1.JBO.20.8.080502 PG 4 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA CT0VV UT WOS:000362516700002 PM 26263413 ER PT J AU Lloyd, WR Agarwal, S Nigwekar, SU Esmonde-White, K Loder, S Fagan, S Goverman, J Olsen, BR Jumlongras, D Morris, MD Levi, B AF Lloyd, William R. Agarwal, Shailesh Nigwekar, Sagar U. Esmonde-White, Karen Loder, Shawn Fagan, Shawn Goverman, Jeremy Olsen, Bjorn R. Jumlongras, Dolrudee Morris, Michael D. Levi, Benjamin TI Raman spectroscopy for label-free identification of calciphylaxis SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE Raman spectroscopy; calciphylaxis; near-infrared light; light scatter; tissues ID CALCIFIC UREMIC ARTERIOLOPATHY; SODIUM-THIOSULFATE; IN-VIVO; DISEASE AB Calciphylaxis is a painful, debilitating, and premorbid condition, which presents as calcified vasculature and soft tissues. Traditional diagnosis of calciphylaxis lesions requires an invasive biopsy, which is destructive, time consuming, and often leads to exacerbation of the condition and infection. Furthermore, it is difficult to find small calcifications within a large wound bed. To address this need, a noninvasive diagnostic tool may help clinicians identify ectopic calcified mineral and determine the disease margin. We propose Raman spectroscopy as a rapid, point-of-care, noninvasive, and label-free technology to detect calciphylaxis mineral. Debrided calciphylactic tissue was collected from six patients and assessed by microcomputed tomography (micro-CT). Micro-CT confirmed extensive deposits in three specimens, which were subsequently examined with Raman spectroscopy. Raman spectra confirmed that deposits were consistent with carbonated apatite, consistent with the literature. Raman spectroscopy shows potential as a noninvasive technique to detect calciphylaxis in a clinical environment. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. C1 [Lloyd, William R.; Morris, Michael D.] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA. [Agarwal, Shailesh; Loder, Shawn; Levi, Benjamin] Univ Michigan, Sch Med, Dept Surg, Ann Arbor, MI 48109 USA. [Nigwekar, Sagar U.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Esmonde-White, Karen] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA. [Fagan, Shawn; Goverman, Jeremy] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Olsen, Bjorn R.; Jumlongras, Dolrudee] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. RP Morris, MD (reprint author), Univ Michigan, Dept Chem, 930 North Univ Ave, Ann Arbor, MI 48109 USA. EM mdmorris@umich.edu; blevi@umich.edu FU NIH NIGMS [K08GM109105-01]; Plastic Surgery Foundation National Endowment Award; American Association of Plastic Surgery Academic Scholarship Award; DOD [W81XWH-14-DMRDP-CRMRP-NMSIRA]; Michigan Diabetes Research and Training Center; NIH/NIDDK [2P30 DK020572]; NIH LRP; NIH F32; Coller Society; National Kidney Foundation; American Heart Association; NIH [R01 AR052010] FX Funding is gratefully acknowledged from NIH NIGMS K08GM109105-01, Plastic Surgery Foundation National Endowment Award, American Association of Plastic Surgery Academic Scholarship Award, DOD: W81XWH-14-DMRDP-CRMRP-NMSIRA (to B. L.), a Pilot and Feasibility Grant from the Michigan Diabetes Research and Training Center, subgrant of NIH/NIDDK 2P30 DK020572 (K. E. W.), the NIH LRP, NIH F32, Coller Society, and the National Kidney Foundation and the American Heart Association (to S. U. N.), and NIH R01 AR052010 (to M. D. M.). NR 25 TC 2 Z9 2 U1 0 U2 3 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD AUG PY 2015 VL 20 IS 8 AR 080501 DI 10.1117/1.JBO.20.8.080501 PG 3 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA CT0VV UT WOS:000362516700001 PM 26263412 ER PT J AU Thornton, PS Stanley, CA De Leon, DD Harris, D Haymond, MW Hussain, K Levitsky, LL Murad, MH Rozance, PJ Simmons, RA Sperling, MA Weinstein, DA White, NH Wolfsdorf, JI AF Thornton, Paul S. Stanley, Charles A. De Leon, Diva D. Harris, Deborah Haymond, Morey W. Hussain, Khalid Levitsky, Lynne L. Murad, Mohammad H. Rozance, Paul J. Simmons, Rebecca A. Sperling, Mark A. Weinstein, David A. White, Neil H. Wolfsdorf, Joseph I. TI Recommendations from the Pediatric Endocrine Society for Evaluation and Management of Persistent Hypoglycemia in Neonates, Infants, and Children SO JOURNAL OF PEDIATRICS LA English DT Article ID HYPERINSULINEMIC HYPOGLYCEMIA; CONGENITAL HYPERINSULINISM; GLYCEMIC RESPONSE; 24-HOUR FAST; FOLLOW-UP; GLUCOSE; DIAGNOSIS; FAILURE; GLUCAGON; PRETERM C1 [Thornton, Paul S.] Cook Childrens Med Ctr, Div Endocrinol, Ft Worth, TX 76104 USA. [Stanley, Charles A.; De Leon, Diva D.] Childrens Hosp Philadelphia, Div Endocrinol, Philadelphia, PA 19104 USA. [Harris, Deborah] Waikato Dist Hlth Board, Newborn Intens Care Unit, Hamilton, New Zealand. [Haymond, Morey W.] Texas Childrens Hosp, Childrens Nutr Res Ctr, Houston, TX 77030 USA. [Hussain, Khalid] Great Ormond St Hosp Children NHS Fdn Trust, Dept Endocrinol, London, England. [Levitsky, Lynne L.] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. [Murad, Mohammad H.] Mayo Clin, Div Prevent Med, Rochester, MN USA. [Rozance, Paul J.] Univ Colorado, Div Neonatol, Sch Med, Aurora, CO USA. [Simmons, Rebecca A.] Childrens Hosp Philadelphia, Div Neonatol, Philadelphia, PA 19104 USA. [Sperling, Mark A.] Childrens Hosp Pittsburgh, Div Endocrinol Diabet & Metab, Pittsburgh, PA 15213 USA. [Weinstein, David A.] Univ Florida, Coll Med, Glycogen Storage Dis Program, Gainesville, FL USA. [White, Neil H.] Washington Univ, Dept Pediat & Med, St Louis, MO USA. [Wolfsdorf, Joseph I.] Boston Childrens Hosp, Div Endocrinol, Boston, MA USA. RP Thornton, PS (reprint author), Cook Childrens Med Ctr, 1500 Cooper St,Second Floor, Ft Worth, TX 76104 USA. EM Paul.thornton@cookchildrens.org NR 39 TC 28 Z9 28 U1 1 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD AUG PY 2015 VL 167 IS 2 BP 238 EP 245 DI 10.1016/j.jpeds.2015.03.057 PG 8 WC Pediatrics SC Pediatrics GA CT0AF UT WOS:000362455300006 PM 25957977 ER PT J AU Baker, JN Levine, DR Hinds, PS Weaver, MS Cunningham, MJ Johnson, L Anghelescu, D Mandrell, B Gibson, DV Jones, B Wolfe, J Feudtner, C Friebert, S Carter, B Kane, JR AF Baker, Justin N. Levine, Deena R. Hinds, Pamela S. Weaver, Meaghann S. Cunningham, Melody J. Johnson, Liza Anghelescu, Doralina Mandrell, Belinda Gibson, Deborah V. Jones, Barbara Wolfe, Joanne Feudtner, Chris Friebert, Sarah Carter, Brian Kane, Javier R. TI Research Priorities in Pediatric Palliative Care SO JOURNAL OF PEDIATRICS LA English DT Article ID CHILDREN; DELPHI; LIFE; END; GUIDELINES; ATTITUDES; BARRIERS; HOSPICE AB Objective To synthesize the perspectives of a broad range of pediatric palliative care (PPC) clinicians and parents, to formulate a consensus on prioritization of the PPC research agenda. Study design A 4-round modified Delphi online survey was administered to PPC experts and to parents of children who had received PPC. In round 1, research priorities were generated spontaneously. Rounds 2 and 3 then served as convergence rounds to synthesize priorities. In round 4, participants were asked to rank the research priorities that had reached at least 80% consensus. Results A total of 3093 concepts were spontaneously generated by 170 experts and 72 parents in round 1 (65.8% response rate [RR]). These concepts were thematically organized into 78 priorities and recirculated for round 2 ratings (n = 130; 53.7% RR). Round 3 achieved response stability, with 31 consensus priorities oscillating within 10% of the mode (n = 98; 75.4% RR). Round 4 resulted in consensus recognition of 20 research priorities, which were thematically grouped as decision making, care coordination, symptom management, quality improvement, and education. Conclusions This modified Delphi survey used professional and parental consensus to identify preeminent PPC research priorities. Attentiveness to these priorities may help direct resources and efforts toward building a formative evidence base. Investigating PPC implementation approaches and outcomes can help improve the quality of care services for children and families. C1 [Baker, Justin N.; Levine, Deena R.; Weaver, Meaghann S.; Johnson, Liza; Anghelescu, Doralina; Gibson, Deborah V.] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA. [Baker, Justin N.; Levine, Deena R.; Weaver, Meaghann S.; Johnson, Liza; Anghelescu, Doralina; Gibson, Deborah V.] St Jude Childrens Res Hosp, Div Qual Life & Palliat Care, Memphis, TN 38105 USA. [Hinds, Pamela S.] Childrens Natl Hlth Syst, Ctr Translat Res, Dept Nursing Res & Qual Outcomes, Washington, DC USA. [Cunningham, Melody J.] Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Le Bonheur Childrens Hosp, Memphis, TN 38163 USA. [Mandrell, Belinda] St Jude Childrens Res Hosp, Dept Pediat Med, Div Nursing Res, Memphis, TN 38105 USA. [Jones, Barbara] Univ Texas Austin, Sch Social Work, Austin, TX 78712 USA. [Wolfe, Joanne] Dana Farber Canc Inst, Div Pediat Palliat Care, Dept Psychosocial & Palliat Care, Boston, MA 02115 USA. [Wolfe, Joanne] Boston Childrens Hosp, Dept Med, Boston, MA USA. [Feudtner, Chris] Childrens Hosp Philadelphia, Div Pediat Palliat Care, Philadelphia, PA 19104 USA. [Friebert, Sarah] Akron Childrens Hosp, Haslinger Div Pediat Palliat Care, Akron, OH USA. [Carter, Brian] Mercy Hosp Ctr & Clin, Dept Neonatol, Kansas City, KS USA. [Carter, Brian] Mercy Hosp Ctr & Clin, Dept Bioeth, Kansas City, KS USA. [Kane, Javier R.] Baylor Scott & White Hlth, McLane Childrens Hosp & Clin, Dept Pediat, Temple, TX USA. [Kane, Javier R.] Texas A&M Hlth Sci Ctr, Coll Med, Temple, TX USA. RP Baker, JN (reprint author), St Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA. EM Justin.Baker@stjude.org OI Carter, Brian/0000-0003-0539-9164; Baker, Justin/0000-0002-6584-6483 FU American Lebanese Syrian Associated Charities FX Supported by American Lebanese Syrian Associated Charities. The authors declare no conflicts of interest. NR 20 TC 5 Z9 5 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD AUG PY 2015 VL 167 IS 2 BP 467 EP + DI 10.1016/j.jpeds.2015.05.002 PG 7 WC Pediatrics SC Pediatrics GA CT0AF UT WOS:000362455300049 PM 26028284 ER PT J AU Hess, DR AF Hess, Dean R. TI Year in Review 2014: Patient Safety SO RESPIRATORY CARE LA English DT Review DE handoffs; patient safety; perioperative obstructive sleep apnea; pressure injury; protocols; readmissions ID OBSTRUCTIVE SLEEP-APNEA; POSITIVE AIRWAY PRESSURE; NONINVASIVE VENTILATION; MECHANICAL VENTILATION; PULMONARY-DISEASE; STOP-BANG; I-PASS; CARE; READMISSIONS; PERFORMANCE AB The topic of patient safety has received much attention in recent years. There are a number of areas in which the subject of patient safety impacts respiratory care practice. This paper focuses on articles published in 2014 related to pressure injury, handoffs, protocols and multidisciplinary teams, perioperative obstructive sleep apnea, and readmissions. (C) 2015 Daedalus Enterprises C1 [Hess, Dean R.] Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02114 USA. [Hess, Dean R.] Harvard Univ, Sch Med, Boston, MA USA. RP Hess, DR (reprint author), Massachusetts Gen Hosp, Resp Care Serv, Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM dhess@partners.org NR 34 TC 0 Z9 0 U1 2 U2 4 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 EI 1943-3654 J9 RESP CARE JI Respir. Care PD AUG PY 2015 VL 60 IS 8 BP 1197 EP 1202 DI 10.4187/respcare.04235 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CS7MG UT WOS:000362267100021 PM 26038594 ER PT J AU Wu, MV Sahay, A Duman, RS Hen, R AF Wu, Melody V. Sahay, Amar Duman, Ronald S. Hen, Rene TI Functional Differentiation of Adult-Born Neurons along the Septotemporal Axis of the Dentate Gyrus SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID ANTERIOR HIPPOCAMPAL VOLUME; DORSAL-VENTRAL AXIS; NEURAL STEM-CELLS; NEWLY GENERATED NEURONS; CA1 AXONAL PROJECTIONS; LONG-TERM POTENTIATION; PATTERN SEPARATION; MOUSE HIPPOCAMPUS; RAT HIPPOCAMPUS; DORSOVENTRAL AXIS AB Over the past several decades, the proliferation and integration of adult-born neurons into existing hippocampal circuitry has been implicated in a wide range of behaviors, including novelty recognition, pattern separation, spatial learning, anxiety behaviors, and antidepressant response. In this review, we suggest that the diversity in behavioral requirements for new neurons may be partly caused by separate functional roles of individual neurogenic niches. Growing evidence shows that the hippocampal formation can be compartmentalized not only along the classic trisynaptic circuit, but also along a longitudinal septotemporal axis. We suggest that subpopulations of hippocampal adult-born neurons may be specialized for distinct mnemonic- or mood-related behavioral tasks. We will examine the literature supporting a functional and anatomical dissociation of the hippocampus along the longitudinal axis and discuss techniques to functionally dissect the roles of adult-born hippocampal neurons in these distinct subregions. C1 [Wu, Melody V.; Hen, Rene] Columbia Univ, Dept Psychiat, New York, NY 10027 USA. [Wu, Melody V.; Hen, Rene] New York State Psychiat Inst & Hosp, Div Integrat Neurosci, New York, NY 10032 USA. [Sahay, Amar] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Sahay, Amar] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Sahay, Amar] Harvard Stem Cell Inst, Boston, MA 02115 USA. [Sahay, Amar] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Duman, Ronald S.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Hen, Rene] Columbia Univ, Dept Neurosci, New York, NY 10027 USA. [Hen, Rene] Columbia Univ, Dept Pharmacol, New York, NY 10027 USA. RP Hen, R (reprint author), Columbia Univ, Dept Psychiat, New York, NY 10027 USA. EM rh95@columbia.edu FU U.S. National Institutes of Health [1-R01MH104175]; Ellison Medical Foundation New Scholar in Aging; Whitehall Foundation; National Institute of Mental Health [RO1MH093897, R37MH45481, R37 MH068542 [MERIT]]; State of Connecticut; National Institute on Aging [R01 AG043688]; National Institute of Neurological Disorders and Stroke [R01NS081203-01A1]; NYSTEM [C029157]; Hope for Depression Research Foundation [RGA11-024] FX A.S. is supported by a U.S. National Institutes of Health Grant 1-R01MH104175, the Ellison Medical Foundation New Scholar in Aging, and a Whitehall Foundation grant. R.S.D. is supported by the National Institute of Mental Health (RO1MH093897 and R37MH45481) and the State of Connecticut, and is a consultant for Taisho, Naurex, and Sunovion. R.H. is supported by the National Institute for Mental Health (R37 MH068542 [MERIT]), the National Institute on Aging (R01 AG043688), the National Institute of Neurological Disorders and Stroke (R01NS081203-01A1), NYSTEM (C029157), and the Hope for Depression Research Foundation (RGA11-024). R.H. is a consultant for Roche and Lundbeck. NR 160 TC 2 Z9 2 U1 3 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD AUG PY 2015 VL 7 IS 8 AR a018978 DI 10.1101/cshperspect.a018978 PG 17 WC Cell Biology SC Cell Biology GA CS4EJ UT WOS:000362027800005 PM 26238355 ER PT J AU Matthews, KA Tonsho, M Madsen, JC AF Matthews, Kristin A. Tonsho, Makoto Madsen, Joren C. TI New-Onset Diabetes Mellitus After Transplantation in a Cynomolgus Macaque (Macaca fasicularis) SO COMPARATIVE MEDICINE LA English DT Article ID RENAL-TRANSPLANTATION; INSULIN-SECRETION; RISK-FACTORS; KIDNEY-TRANSPLANTATION; LIVER-TRANSPLANTATION; GLUCOSE-METABOLISM; STEROID WITHDRAWAL; TACROLIMUS; RECIPIENTS; CYCLOSPORINE AB A 5.5-y-old intact male cynomolgus macaque (Macaca fasicularis) presented with inappetence and weight loss 57 d after heterotopic heart and thymus transplantation while receiving an immunosuppressant regimen consisting of tacrolimus, mycophenolate mofetil, and methylprednisolone to prevent graft rejection. A serum chemistry panel, a glycated hemoglobin test, and urinalysis performed at presentation revealed elevated blood glucose and glycated hemoglobin (HbA1c) levels (727 mg/dL and 10.1%, respectively), glucosuria, and ketonuria. Diabetes mellitus was diagnosed, and insulin therapy was initiated immediately. The macaque was weaned off the immunosuppressive therapy as his clinical condition improved and stabilized. Approximately 74 d after discontinuation of the immunosuppressants, the blood glucose normalized, and the insulin therapy was stopped. The animal's blood glucose and HbA1c values have remained within normal limits since this time. We suspect that our macaque experienced new-onset diabetes mellitus after transplantation, a condition that is commonly observed in human transplant patients but not well described in NHP. To our knowledge, this report represents the first documented case of new-onset diabetes mellitus after transplantation in a cynomolgus macaque. C1 [Matthews, Kristin A.] Massachusetts Gen Hosp, Ctr Comparat Med, Boston, MA 02114 USA. [Tonsho, Makoto; Madsen, Joren C.] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. [Madsen, Joren C.] Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Boston, MA 02114 USA. RP Matthews, KA (reprint author), Massachusetts Gen Hosp, Ctr Comparat Med, Boston, MA 02114 USA. EM kamatthews@mgh.harvard.edu FU National Heart, Lung, and Blood Institute [P01HL018646]; National Institute of Allergy and Infectious Disease, NIH [U01AI094374] FX This work was supported in part by grants from the National Heart, Lung, and Blood Institute (P01HL018646) and the National Institute of Allergy and Infectious Disease (U01AI094374), NIH. We thank Dr Tatsuo Kawai for his assistance in the preparation of this manuscript. NR 45 TC 0 Z9 0 U1 2 U2 4 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD AUG PY 2015 VL 65 IS 4 BP 352 EP 356 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA CS7BQ UT WOS:000362238900009 PM 26310466 ER PT J AU Kim, JI Rothstein, DM Markmann, JF AF Kim, James I. Rothstein, David M. Markmann, James F. TI Role of B cells in tolerance induction SO CURRENT OPINION IN ORGAN TRANSPLANTATION LA English DT Review DE IL-10; regulatory B cells; rituximab; transplant tolerance ID REGULATORY T-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; KIDNEY-TRANSPLANT RECIPIENTS; ACUTE CELLULAR REJECTION; B10 CELLS; ALLOGRAFT SURVIVAL; APOPTOTIC CELLS; CUTTING EDGE; LUPUS MICE; TGF-BETA AB Purpose of reviewB cells are known to play a central role in humoral immunity and to boost cellular immunity, however, in a variety of experimental models, B-cell subsets ameliorate inflammation and autoimmune disease, indicating that they can also play a regulatory role. Here, we highlight the advances in regulatory B-cell (Breg) biology of the past year with an emphasis on findings pertinent to transplantation. Several recent observations highlight the relevance to clinical transplantation. Data from at least three independent groups demonstrated that spontaneously tolerant renal transplant recipients exhibit a peripheral blood B-cell signature although the significance of these data remains unclear. Moreover, new data suggest that regulatory B cells may serve as a biomarker for long-term allograft outcomes. Finally, recent evidence suggesting that plasma cells may be an essential component of Bregs raises new concerns about targeting antibody producing cells.Recent findingsWe describe new information on Breg mechanisms of action to suppress the alloresponse, signals to expand Bregs in vitro, and more functional evidence of Breg involvement in operationally tolerant kidney patients and in maintaining stable allograft function.SummaryAlthough lymphocyte depletion remains central to tolerance induction therapy, the sparing or expansion of regulatory B cells may be an additional strategy to preempt graft rejection. C1 [Kim, James I.; Markmann, James F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Transplantat Sci, Boston, MA USA. [Rothstein, David M.] Univ Pittsburgh, Sch Med, Thomas E Starzl Transplantat Inst, Pittsburgh, PA USA. RP Kim, JI (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jkim35@mgh.harvard.edu FU NIH [AI097361, AI057851] FX The authors thank members of their respective laboratories for conversations, which led to the writing of this review. This work was supported by NIH Grants AI097361 to D.M.R. and AI057851 to J.F.M. NR 71 TC 7 Z9 8 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1087-2418 EI 1531-7013 J9 CURR OPIN ORGAN TRAN JI Curr. Opin. Organ Transpl. PD AUG PY 2015 VL 20 IS 4 BP 369 EP 375 DI 10.1097/MOT.0000000000000204 PG 7 WC Transplantation SC Transplantation GA CS7KB UT WOS:000362261400001 PM 26107970 ER PT J AU Madariaga, MLL Kreisel, D Madsen, JC AF Madariaga, Maria Lucia L. Kreisel, Daniel Madsen, Joren C. TI Organ-specific differences in achieving tolerance SO CURRENT OPINION IN ORGAN TRANSPLANTATION LA English DT Review DE heart; kidney; lung; organ specificity; tolerance; transplantation ID REGULATORY T-CELLS; CARDIAC ALLOGRAFT VASCULOPATHY; TUBULAR EPITHELIAL-CELLS; BRONCHIOLITIS OBLITERANS SYNDROME; CLINICAL OPERATIONAL TOLERANCE; HEART-KIDNEY TRANSPLANTATION; PLASMACYTOID DENDRITIC CELLS; HEPATIC STELLATE CELLS; MINIATURE SWINE; LIVER-TRANSPLANTATION AB Purpose of reviewWhen it comes to tolerance induction, kidney allografts behave differently from heart allografts that behave differently from lung allografts. Here, we examine how and why different organ allografts respond differently to the same tolerance induction protocol.Recent findingsAllograft tolerance has been achieved in experimental and clinical kidney transplantation. Inducing tolerance in experimental recipients of heart and lung allografts has, however, proven to be more challenging. New protocols being developed in nonhuman primates based on mixed chimerism and cotransplantation of tolerogenic organs may provide mechanistic insights to help overcome these challenges.SummaryTolerance induction protocols that are successful in patients transplanted with tolerance-prone' organs such as kidneys and livers will most likely not succeed in recipients of tolerance-resistant' organs such as hearts and lungs. Separate clinical trials using more robust tolerance protocols will be required to achieve tolerance in heart and lung recipients. C1 [Madariaga, Maria Lucia L.; Madsen, Joren C.] Massachusetts Gen Hosp, Dept Surg, Ctr Transplantat Sci, Boston, MA 02114 USA. [Kreisel, Daniel] Washington Univ, Sch Med, Dept Surg, Div Cardiothorac Surg, St Louis, MO 63110 USA. [Madsen, Joren C.] Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Boston, MA 02114 USA. RP Madsen, JC (reprint author), Massachusetts Gen Hosp, WHT 05-510C,55 Fruit St, Boston, MA 02114 USA. EM jcmadsen@mgh.harvard.edu FU National Heart, Lung, and Blood Institute of National Institutes of Health [P01HL18646, R01HL113931, R01HL094601]; National Institute of Allergy and Infectious Disease of National Institutes of Health [U01AI94374]; Thoracic Surgery Foundation for Research and Education; International Heart and Lung Transplantation Society; National Heart, Lung, and Blood Institute of the National Institutes of Health [F32HL117540] FX This work was supported in part by grants from the National Heart, Lung, and Blood Institute (P01HL18646, R01HL113931, R01HL094601) and the National Institute of Allergy and Infectious Disease (U01AI94374) of National Institutes of Health, and from the Thoracic Surgery Foundation for Research and Education. M.L.L.M. is an Edward D. Churchill Surgical Research Fellow, Massachusetts General Hospital, recipient of a fellowship from the International Heart and Lung Transplantation Society and was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number F32HL117540. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 115 TC 1 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1087-2418 EI 1531-7013 J9 CURR OPIN ORGAN TRAN JI Curr. Opin. Organ Transpl. PD AUG PY 2015 VL 20 IS 4 BP 392 EP 399 DI 10.1097/MOT.0000000000000206 PG 8 WC Transplantation SC Transplantation GA CS7LU UT WOS:000362265900001 PM 26147678 ER PT J AU Newell, KA Turka, LA AF Newell, Kenneth A. Turka, Laurence A. TI Tolerance signatures in transplant recipients SO CURRENT OPINION IN ORGAN TRANSPLANTATION LA English DT Review DE biomarkers; gene expression; polychromatic flowcytometry; tolerance ID DONOR LIVER-TRANSPLANTATION; BLOOD MONONUCLEAR-CELLS; OPERATIONAL TOLERANCE; RENAL-TRANSPLANT; LONG-TERM; KIDNEY-TRANSPLANTATION; T-CELLS; IMMUNOSUPPRESSIVE DRUGS; ALLOGRAFT SURVIVAL; UNITED-STATES AB Purpose of reviewThe intent of this review was to describe biomarkers that predict or identify individuals who exhibit tolerance to a transplanted organ. The identification of tolerance biomarkers would spare some individuals the toxicity of immunosuppressive agents, enhance the safety of studies to induce tolerance, and provide insights into mechanisms of tolerance that may aid in designing new regimens.Recent findingsStudies of tolerant kidney transplant recipients have revealed an association with B cells. More recent studies have suggested that these B cells may be less mature than from those in nontolerant recipients, and especially suited to suppress alloimmune responses. Biomarkers in tolerant liver transplant patients appear to be distinct from those associated renal tolerance. Most reports have identified an association with natural killer and/or T cells rather than B cells. Recent data indicate biomarkers associated with iron homeostasis within the transplanted liver more accurately predict the tolerant state than do biomarkers expressed in the blood, suggesting that the renal allograft itself, which is infrequently sampled, would be informative.SummaryGiven the encouraging progress in identifying tolerance biomarkers, it will be important to validate these markers in larger studies of transplant recipients undergoing prospective minimization or withdrawal of immunosuppression. C1 [Newell, Kenneth A.] Emory Univ, Dept Surg, Atlanta, GA 30322 USA. [Turka, Laurence A.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Turka, Laurence A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Immune Tolerance Network, Boston, MA USA. RP Newell, KA (reprint author), Emory Univ, Dept Surg, 101 Woodruff Circle,Suite 5105 WMB, Atlanta, GA 30322 USA. EM kanewel@emory.edu FU National Institute of Allergy and Infectious Diseases of the National Institutes of Health [UM1AI109565] FX Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UM1AI109565. NR 35 TC 0 Z9 0 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1087-2418 EI 1531-7013 J9 CURR OPIN ORGAN TRAN JI Curr. Opin. Organ Transpl. PD AUG PY 2015 VL 20 IS 4 BP 400 EP 405 DI 10.1097/MOT.0000000000000207 PG 6 WC Transplantation SC Transplantation GA CS7KK UT WOS:000362262300001 PM 26107969 ER PT J AU Elias, N Cosimi, AB Kawai, T AF Elias, Nahel Cosimi, A. Benedict Kawai, Tatsuo TI Clinical trials for induction of renal allograft tolerance SO CURRENT OPINION IN ORGAN TRANSPLANTATION LA English DT Review DE allograft tolerance; chimerism; hematopoietic stem cell transplantation; kidney transplantation; regulatory T cells ID REGULATORY T-CELLS; BONE-MARROW-TRANSPLANTATION; TOTAL-LYMPHOID IRRADIATION; MAINTENANCE IMMUNOSUPPRESSION; MIXED CHIMERISM; RECIPIENTS; KIDNEY; INFUSION; DISEASE; PROFILE AB Purpose of reviewThis review summarizes the current state of clinical trials for tolerance induction of human leukocyte antigen-matched or mismatched renal allografts via peritransplant infusion of donor bone marrow-derived products. Recent efforts to apply infusion of expanded regulatory T-cell preparations to minimize immunosuppressive dosages are also reviewed.Recent findingsThree centers in the United States have reported clinical trials for tolerance induction in recipients of living donor kidney transplants via donor hematopoietic stem cell transplantation. They have observed varying degrees of successful renal allograft tolerance induction following the establishment of either transient or persistent donor chimerism.A more recent clinical trial planned to evaluate administration of regulatory T cells to harness the immune response has recently been initiated in eight centers in Europe and the United States.SummaryTolerance induction in clinical kidney transplantation from live donors has been achieved by donor hematopoietic stem cell transplantation. Improving the consistency and safety of tolerance induction and extending successful protocols to other organs, as well as to organs from deceased donors, are critical next steps to bringing tolerance to a wider range of clinical applications. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplant Ctr, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Transplant Surg,Dept Surg, Cambridge, MA 02138 USA. RP Kawai, T (reprint author), Massachusetts Gen Hosp, MGH White 521,55 Fruit St, Boston, MA 02114 USA. EM tkawai@mgh.harvard.edu NR 35 TC 3 Z9 4 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1087-2418 EI 1531-7013 J9 CURR OPIN ORGAN TRAN JI Curr. Opin. Organ Transpl. PD AUG PY 2015 VL 20 IS 4 BP 406 EP 411 DI 10.1097/MOT.0000000000000211 PG 6 WC Transplantation SC Transplantation GA CS7KK UT WOS:000362262300002 PM 26147679 ER PT J AU Giugliano, RP Wiviott, SD Blazing, MA Murphy, SA Zhou, J White, JA Musliner, TA Tershakovec, AJ Cannon, CP Braunwald, E AF Giugliano, R. P. Wiviott, S. D. Blazing, M. A. Murphy, S. A. Zhou, J. White, J. A. Musliner, T. A. Tershakovec, A. J. Cannon, C. P. Braunwald, E. CA IMPROVE IT Investigators TI Safety and efficacy of long-term very low achieved LDL-C in the IMPROVE IT trial SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 29-SEP 02, 2015 CL London, ENGLAND SP European Soc Cardiol C1 [Giugliano, R. P.; Wiviott, S. D.; Murphy, S. A.; Zhou, J.; Cannon, C. P.; Braunwald, E.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Blazing, M. A.; White, J. A.] Duke Clin Res Inst, Durham, NC USA. [Musliner, T. A.; Tershakovec, A. J.] Merck & Co Inc, Kenilworth, NJ USA. NR 0 TC 2 Z9 2 U1 0 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 2015 VL 36 SU 1 MA 68 BP 2 EP 2 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR3BL UT WOS:000361205101001 ER PT J AU Engels, EB Vegh, EM Van Deursen, CJM Merkely, B Vernooy, K Singh, JP Prinzen, FW AF Engels, E. B. Vegh, E. M. Van Deursen, C. J. M. Merkely, B. Vernooy, K. Singh, J. P. Prinzen, F. W. TI T-wave area as biomarker of clinical response to cardiac resynchronization therapy SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 29-SEP 02, 2015 CL London, ENGLAND SP European Soc Cardiol C1 [Engels, E. B.; Prinzen, F. W.] Maastricht Univ, Physiol, NL-6200 MD Maastricht, Netherlands. [Vegh, E. M.; Singh, J. P.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Van Deursen, C. J. M.; Vernooy, K.] MUMC, Cardiol, Maastricht, Netherlands. [Merkely, B.] Semmelweis Univ, Ctr Heart, H-1085 Budapest, Hungary. 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 2015 VL 36 SU 1 MA P491 BP 50 EP 51 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR3BL UT WOS:000361205101176 ER PT J AU O'Donnell, D Leclercq, C Lunati, M Landolina, M Lercher, P Rordorf, R McSpadden, L Jordan, C Singh, J Pappone, C AF O'Donnell, D. Leclercq, C. Lunati, M. Landolina, M. Lercher, P. Rordorf, R. McSpadden, L. Jordan, C. Singh, J. Pappone, C. TI Differences in interventricular electrical conduction delays and conduction pattern along a quadripolar left ventricular lead during right ventricular paced vs. intrinsic ventricular rhythm SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 29-SEP 02, 2015 CL London, ENGLAND SP European Soc Cardiol C1 [O'Donnell, D.] Austin Hlth Hosp, Cardiol, Melbourne, Vic, Australia. [Leclercq, C.] Univ Hosp Rennes, Cardiol, Rennes, France. [Lunati, M.] Osped Niguarda Ca Granda, Cardiac, Milan, Italy. [Landolina, M.] Maggiore Hosp Crema, Cardiol, Crema, Italy. [Lercher, P.] Med Univ Graz, Graz, Austria. [Rordorf, R.] Policlin Fdn San Matteo IRCCS, Cardiac, Pavia, Italy. [McSpadden, L.; Jordan, C.] St Jude Med, Res, Sylmar, CA USA. [Singh, J.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Pappone, C.] Maria Cecilia Hosp, Arrhythmol, Cotignola, Italy. RI Pappone, Carlo/J-9853-2016 OI Pappone, Carlo/0000-0002-0901-6135 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 2015 VL 36 SU 1 MA P502 BP 53 EP 54 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR3BL UT WOS:000361205101187 ER PT J AU Giugliano, RP Wiviott, SD Fuchs, CS Wagner, AJ Goessling, W White, JA Musliner, TA Tershakovec, AM Blazing, MA Braunwald, E AF Giugliano, R. P. Wiviott, S. D. Fuchs, C. S. Wagner, A. J. Goessling, W. White, J. A. Musliner, T. A. Tershakovec, A. M. Blazing, M. A. Braunwald, E. CA IMPROVE IT Trial Investigators TI Prospectivev evaluation of cancer in 18,144 patients randomized to ezetimibe vs placebo: a prespecified analysis from the IMPROVE IT trial SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 29-SEP 02, 2015 CL London, ENGLAND SP European Soc Cardiol C1 [Giugliano, R. P.; Wiviott, S. D.; Braunwald, E.] Brigham & Womens Hosp, Dept Med, TIMI Study Grp, Cardiovasc Div, Boston, MA 02115 USA. [Fuchs, C. S.; Wagner, A. J.; Goessling, W.] Dana Farber Canc Inst, Boston, MA 02115 USA. [White, J. A.; Blazing, M. A.] Duke Clin Res Inst, Durham, NC USA. [Musliner, T. A.; Tershakovec, A. M.] Merck & Co Inc, Kenilworth, NJ USA. NR 0 TC 3 Z9 3 U1 1 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 2015 VL 36 SU 1 MA P1131 BP 181 EP 181 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR3BL UT WOS:000361205102067 ER PT J AU Sanders-Van Wijk, S Lupon, J Januzzi, JL De Antonio, M Brunner-La Rocca, HP Gaggin, H Galan, A Shah, R Pfisterer, M Bayes-Genis, A AF Sanders-Van Wijk, S. Lupon, J. Januzzi, J. L. De Antonio, M. Brunner-La Rocca, H. P. Gaggin, H. Galan, A. Shah, R. Pfisterer, M. Bayes-Genis, A. TI ST2-R2 score: degree of reverse remodelling and 4-year survival in patients with heart failure. A multicenter study SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 29-SEP 02, 2015 CL London, ENGLAND SP European Soc Cardiol C1 [Sanders-Van Wijk, S.; Brunner-La Rocca, H. P.] Maastricht Univ, Med Ctr, NL-6200 MD Maastricht, Netherlands. [Lupon, J.; De Antonio, M.; Galan, A.; Bayes-Genis, A.] Germans Trias & Pujol Univ Hosp, Badalona, Spain. [Januzzi, J. L.; Gaggin, H.; Shah, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pfisterer, M.] Univ Basel Hosp, CH-4031 Basel, 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 2015 VL 36 SU 1 MA P1139 BP 183 EP 183 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR3BL UT WOS:000361205102075 ER PT J AU Kostis, JB Sargsyan, D Kostis, WJ AF Kostis, J. B. Sargsyan, D. Kostis, W. J. TI Association of orthostatic hypertension with cardiovascular and all cause mortality in the systolic hypertension in the elderly program SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 29-SEP 02, 2015 CL London, ENGLAND SP European Soc Cardiol C1 [Kostis, J. B.; Sargsyan, D.] Rutgers Robert Wood Johnson Med Sch, Cardiovasc Inst, New Brunswick, NJ USA. [Kostis, W. J.] 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 2015 VL 36 SU 1 MA 1238 BP 191 EP 191 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR3BL UT WOS:000361205102103 ER PT J AU Rafael, A Bartko, P Levine, RA Starobinska, EI Lubitz, SA Milan, DJ AF Rafael, A. Bartko, P. Levine, R. A. Starobinska, E. I. Lubitz, S. A. Milan, D. J. TI Sudden cardiac death and mitral valve prolapse: a single center experience SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 29-SEP 02, 2015 CL London, ENGLAND SP European Soc Cardiol C1 [Rafael, A.; Lubitz, S. A.; Milan, D. J.] Massachusetts Gen Hosp, Arrhythmia Serv, Boston, MA 02114 USA. [Bartko, P.; Levine, R. A.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Starobinska, E. I.] Univ Arizona, Sch Med, Phoenix, AZ 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 2015 VL 36 SU 1 MA P1381 BP 205 EP 206 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR3BL UT WOS:000361205102156 ER PT J AU Storey, RF Bhatt, DL Steg, PG Stone, GW White, HD Gibson, CM Hamm, CW Prats, J Mahaffey, KW Harrington, RA AF Storey, R. F. Bhatt, D. L. Steg, P. G. Stone, G. W. White, H. D. Gibson, C. M. Hamm, C. W. Prats, J. Mahaffey, K. W. Harrington, R. A. CA CHAMPION PHOENIX Investigators TI Characteristics of dyspnoea and associated clinical outcomes in the CHAMPION PHOENIX study SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 29-SEP 02, 2015 CL London, ENGLAND SP European Soc Cardiol C1 [Storey, R. F.] Univ Sheffield, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England. [Bhatt, D. L.] Brigham & Womens Hosp, Dept Med, Cardiovasc Div, TIMI Study Grp, Boston, MA 02115 USA. [Steg, P. G.] Univ Paris Diderot, Paris, France. [Stone, G. W.] Columbia Univ, Med Ctr, New York, NY USA. [White, H. D.] Auckland City Hosp, Auckland, New Zealand. [Gibson, C. M.] Harvard Univ, Sch Med, Boston, MA USA. [Hamm, C. W.] Kerckhoff Heart & Thorax Ctr, Bad Nauheim, Germany. [Prats, J.] Medicines Co, Parsippany, NJ USA. [Mahaffey, K. W.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Harrington, R. A.] Stanford Univ, Med Ctr, Sch Med, Stanford, CA 94305 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 2015 VL 36 SU 1 MA P1497 BP 237 EP 237 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR3BL UT WOS:000361205102272 ER PT J AU Eisen, A Cannon, CP Braunwald, E Steen, DL Zhou, J Dalby, AJ Spinar, J Daga, S Lukas, MA O'Donoghue, ML AF Eisen, A. Cannon, C. P. Braunwald, E. Steen, D. L. Zhou, J. Dalby, A. J. Spinar, J. Daga, S. Lukas, M. A. O'Donoghue, M. L. TI Predictors of failure to use of a high potency statin regimen after an acute coronary syndrome: insights from the SOLID-TIMI 52 trial SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 29-SEP 02, 2015 CL London, ENGLAND SP European Soc Cardiol C1 [Eisen, A.; Cannon, C. P.; Braunwald, E.; Zhou, J.; O'Donoghue, M. L.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Steen, D. L.] Univ Cincinnati, Cincinnati, OH USA. [Dalby, A. J.] Milpk Hosp, Johannesburg, South Africa. [Spinar, J.] Univ Hosp Brno, Brno, Czech Republic. [Daga, S.; Lukas, M. A.] GSK, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2015 VL 36 SU 1 MA P1682 BP 288 EP 288 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR3BL UT WOS:000361205102457 ER PT J AU Shah, R Hellkamp, AS Berkowitz, SD Breithardt, G Fox, KAA Mahaffey, KW Nessel, CC Piccini, JP Singer, DE Patel, MR AF Shah, R. Hellkamp, A. S. Berkowitz, S. D. Breithardt, G. Fox, K. A. A. Mahaffey, K. W. Nessel, C. C. Piccini, J. P. Singer, D. E. Patel, M. R. TI Rivaroxaban vs. warfarin with concomitant aspirin use in patients with atrial fibrillation: findings from the ROCKET AF trial SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 29-SEP 02, 2015 CL London, ENGLAND SP European Soc Cardiol C1 [Shah, R.; Hellkamp, A. S.; Piccini, J. P.; Patel, M. R.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA. [Berkowitz, S. D.] Bayer Healthcare Pharmaceut, Whippany, NJ USA. [Breithardt, G.] Univ Hosp Munster, Munster, Germany. [Fox, K. A. A.] Univ Edinburgh, Royal Infirm Edinburgh, Edinburgh, Midlothian, Scotland. [Mahaffey, K. W.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Nessel, C. C.] Janssen Res & Dev, Raritan, NJ USA. [Singer, D. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Singer, D. E.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2015 VL 36 SU 1 MA 2031 BP 345 EP 345 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR3BL UT WOS:000361205103027 ER PT J AU Boriani, G Glotzer, TV Santini, M West, TM De Melis, M Sepsi, M Gasparini, M Lewalter, T Camm, JA Singer, D AF Boriani, G. Glotzer, T. V. Santini, M. West, T. M. De Melis, M. Sepsi, M. Gasparini, M. Lewalter, T. Camm, J. A. Singer, D. TI Time course of detection of new atrial fibrillation (AF) and AF burden in patients with cardiac implanted electronic devices SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 29-SEP 02, 2015 CL London, ENGLAND SP European Soc Cardiol C1 [Boriani, G.] Univ Bologna, Inst Cardiol, Bologna, Italy. [Glotzer, T. V.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Santini, M.] San Filippo Neri Hosp, Rome, Italy. [West, T. M.; De Melis, M.] Bakken Res Ctr, Maastricht, Netherlands. [Sepsi, M.] Univ Hosp Brno, Brno, Czech Republic. [Gasparini, M.] Clin Inst Humanitas IRCCS, Rozzano, Italy. [Lewalter, T.] Isar Heart Ctr, Munich, Germany. [Camm, J. A.] St Georges Med Sch, London, England. [Singer, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Boriani, Giuseppe/A-4852-2015 OI Boriani, Giuseppe/0000-0002-9820-4815 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 2015 VL 36 SU 1 MA P2115 BP 350 EP 351 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR3BL UT WOS:000361205103047 ER PT J AU Magnani, G Sabatine, MS Bhatt, DL Choen, M Steg, G Storey, R Kuder, J Murphy, S Braunwald, E Bonaca, MP AF Magnani, G. Sabatine, M. S. Bhatt, D. L. Choen, M. Steg, G. Storey, R. Kuder, J. Murphy, S. Braunwald, E. Bonaca, M. P. TI Efficacy and Safety of Ticagrelor for Long-Term Secondary Prevention of Atherothrombotic Events in Relation to Renal Function: Insights from the PEGASUS-TIMI 54 trial SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 29-SEP 02, 2015 CL London, ENGLAND SP European Soc Cardiol C1 [Magnani, G.; Sabatine, M. S.; Bhatt, D. L.; Kuder, J.; Murphy, S.; Braunwald, E.; Bonaca, M. P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp, Boston, MA 02115 USA. [Choen, M.] Newark Beth Israel Med Ctr, Newark, NJ USA. [Steg, G.] Univ Paris Diderot, Paris, France. [Storey, R.] Univ Sheffield, Sheffield, S Yorkshire, England. 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 2015 VL 36 SU 1 MA 3032 BP 520 EP 520 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR3BL UT WOS:000361205104037 ER PT J AU O'Donoghue, ML Bonaca, MP Magnani, G Bhatt, DL Cohen, M Steg, PG Storey, RF Murphy, SM Braunwald, E Sabatine, MS AF O'Donoghue, M. L. Bonaca, M. P. Magnani, G. Bhatt, D. L. Cohen, M. Steg, P. G. Storey, R. F. Murphy, S. M. Braunwald, E. Sabatine, M. S. TI The efficacy and safety of ticagrelor in women versus men with a prior myocardial infarction: insights from the PEGASUS-TIMI 54 trial SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 29-SEP 02, 2015 CL London, ENGLAND SP European Soc Cardiol C1 [O'Donoghue, M. L.; Bonaca, M. P.; Magnani, G.; Bhatt, D. L.; Murphy, S. M.; Braunwald, E.; Sabatine, M. S.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Cohen, M.] Barnabas, Cardiol, W Orange, NJ USA. [Steg, P. G.] Univ Paris Diderot, Paris, France. [Storey, R. F.] Univ Sheffield, Sheffield, S Yorkshire, England. 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 2015 VL 36 SU 1 MA P3317 BP 549 EP 549 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR3BL UT WOS:000361205104141 ER PT J AU Storey, RF Angiolillo, DJ Bonaca, MP Thomas, MR Bhatt, DL Steg, PG Ahsan, AJ Kuder, J Braunwald, E Sabatine, MS AF Storey, R. F. Angiolillo, D. J. Bonaca, M. P. Thomas, M. R. Bhatt, D. L. Steg, P. G. Ahsan, A. J. Kuder, J. Braunwald, E. Sabatine, M. S. TI Ticagrelor 60 mg twice-daily provides effective platelet inhibition in patients with prior myocardial infarction: the PEGASUS-TIMI 54 platelet function substudy SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 29-SEP 02, 2015 CL London, ENGLAND SP European Soc Cardiol C1 [Storey, R. F.; Thomas, M. R.] Univ Sheffield, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England. [Angiolillo, D. J.] Univ Florida, Jacksonville, FL USA. [Bonaca, M. P.; Bhatt, D. L.; Kuder, J.; Braunwald, E.; Sabatine, M. S.] Harvard Univ, Brigham & Womens Hosp, Dept Med, TIMI Study Grp,Cardiovasc Div,Med Sch, Boston, MA 02115 USA. [Steg, P. G.] Univ Paris Diderot, Paris, France. [Ahsan, A. J.] Nottingham Univ Hosp NHS Trust, Nottingham, England. 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 2015 VL 36 SU 1 MA P3318 BP 549 EP 549 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR3BL UT WOS:000361205104142 ER PT J AU Kijlstra, JD Hu, D Mittal, NV Van der Meer, P Garakani, A Domian, IJ AF Kijlstra, J. D. Hu, D. Mittal, N. V. Van der Meer, P. Garakani, A. Domian, I. J. TI Quantitative analysis of cardiomyocyte contractile kinetics and force generation using automated morphologic similarity measure SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 29-SEP 02, 2015 CL London, ENGLAND SP European Soc Cardiol C1 [Kijlstra, J. D.; Hu, D.; Domian, I. J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Mittal, N. V.] Inst Bioengn & Nanotechnol, Singapore, Singapore. [Van der Meer, P.] Univ Med Ctr Groningen, Dept Expt Cardiol, NL-9713 AV Groningen, Netherlands. [Garakani, A.] Reify Corp, Saratoga Springs, 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 2015 VL 36 SU 1 MA P3567 BP 613 EP 614 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR3BL UT WOS:000361205104382 ER PT J AU Benes, J Kotrc, M Melenovsky, V Kautzner, J Jarolim, P AF Benes, J. Kotrc, M. Melenovsky, V. Kautzner, J. Jarolim, P. TI Prognostic role of growth differentiation factor 15 (GDF-15) in obese patients with systolic heart failure (HF) SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 29-SEP 02, 2015 CL London, ENGLAND SP European Soc Cardiol C1 [Benes, J.; Kotrc, M.; Melenovsky, V.; Kautzner, J.] IKEM, Prague, Czech Republic. [Jarolim, P.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Jarolim, P.] Brigham & Womens Hosp, TIMI Grp, 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 2015 VL 36 SU 1 MA P4762 BP 841 EP 841 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR3BL UT WOS:000361205105590 ER PT J AU Schwartzenberg, S Handschumacher, MD Zeng, X Tan, TC Hung, JW AF Schwartzenberg, S. Handschumacher, M. D. Zeng, X. Tan, T. C. Hung, J. W. TI New 3D echo-derived morphometric criteria for discriminating between ischemic and non-ischemic cardiomyopathy SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 29-SEP 02, 2015 CL London, ENGLAND SP European Soc Cardiol C1 [Schwartzenberg, S.] Rabin Med Ctr, Cardiol, Petah Tiqwa, Israel. [Handschumacher, M. D.; Zeng, X.; Tan, T. C.; Hung, J. W.] 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 2015 VL 36 SU 1 MA P5412 BP 937 EP 937 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR3BL UT WOS:000361205106325 ER PT J AU Hucker, WJ Leyton-Mange, JS Mihatov, N Reynolds, WR Albert, CM Lubitz, SA Milan, DJ AF Hucker, W. J. Leyton-Mange, J. S. Mihatov, N. Reynolds, W. R. Albert, C. M. Lubitz, S. A. Milan, D. J. TI Real World Experience with Wearable Cardiac Defibrillators SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 29-SEP 02, 2015 CL London, ENGLAND SP European Soc Cardiol C1 [Hucker, W. J.; Leyton-Mange, J. S.; Mihatov, N.; Lubitz, S. A.; Milan, D. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Reynolds, W. R.] Tufts Med Ctr, Boston, MA USA. [Albert, C. M.] Brigham & Womens Hosp, 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 2015 VL 36 SU 1 MA P5924 BP 1031 EP 1031 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR3BL UT WOS:000361205107039 ER PT J AU May, EAB Giugliano, RP Cannon, CP Murphy, SA Zhou, J Blazing, MA White, JA Tershakovec, AM Musliner, TA Braunwald, E AF May, E. A. Bohula Giugliano, R. P. Cannon, C. P. Murphy, S. A. Zhou, J. Blazing, M. A. White, J. A. Tershakovec, A. M. Musliner, T. A. Braunwald, E. CA TIMI Study Grp TI Achievement of dual LDL-C (< 70 mg/dL) and hs-CRP (< 2 mg/L) goals more frequent with addition of ezetimibe and associated with better outcomes in IMPROVE-IT SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 29-SEP 02, 2015 CL London, ENGLAND SP European Soc Cardiol C1 [May, E. A. Bohula; Giugliano, R. P.; Cannon, C. P.; Murphy, S. A.; Zhou, J.; Braunwald, E.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Blazing, M. A.; White, J. A.] Duke Clin Res Inst, Durham, NC USA. [Tershakovec, A. M.; Musliner, T. A.] Merck & Co Inc, Kenilworth, NJ 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 2015 VL 36 SU 1 MA P6120 BP 1060 EP 1060 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR3BL UT WOS:000361205107144 ER PT J AU Lindner, SM Fordyce, CB Hellkamp, AS Lokhnygina, Y Piccini, JP Breithardt, G Mahaffey, KW Singer, DE Becker, RC Patel, MR AF Lindner, S. M. Fordyce, C. B. Hellkamp, A. S. Lokhnygina, Y. Piccini, J. P. Breithardt, G. Mahaffey, K. W. Singer, D. E. Becker, R. C. Patel, M. R. TI Treatment consistency across levels of baseline renal function with rivaroxaban compared with warfarin: insights from ROCKET AF SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 29-SEP 02, 2015 CL London, ENGLAND SP European Soc Cardiol C1 [Lindner, S. M.; Fordyce, C. B.; Hellkamp, A. S.; Lokhnygina, Y.; Piccini, J. P.; Patel, M. R.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA. [Breithardt, G.] Univ Hosp Munster, Munster, Germany. [Mahaffey, K. W.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Singer, D. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Singer, D. E.] Harvard Univ, Sch Med, Boston, MA USA. [Becker, R. C.] Univ Cincinnati, Coll Med, Cincinnati, OH 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 2015 VL 36 SU 1 MA P6210 BP 1083 EP 1083 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR3BL UT WOS:000361205107226 ER PT J AU Verjans, JW Osborn, EA Ughi, GJ Antoniadis, AP Papafaklis, MI Libby, P Stone, PH Cambria, RP Tearney, GJ Jaffer, FA AF Verjans, J. W. Osborn, E. A. Ughi, G. J. Antoniadis, A. P. Papafaklis, M. I. Libby, P. Stone, P. H. Cambria, R. P. Tearney, G. J. Jaffer, F. A. TI First clinical and intracoronary evaluation of indocyanine green for targeted intravascular near-infrared fluorescence imaging of high-risk atherosclerotic plaques SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology (ESC) CY AUG 29-SEP 02, 2015 CL London, ENGLAND SP European Soc Cardiol C1 [Verjans, J. W.] Univ Med Ctr Utrecht, Cardiol, Utrecht, Netherlands. [Osborn, E. A.; Ughi, G. J.; Cambria, R. P.; Tearney, G. J.; Jaffer, F. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Antoniadis, A. P.; Papafaklis, M. I.; Libby, P.; Stone, P. H.] Brigham & Womens Hosp, Cardiol, 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 2015 VL 36 SU 1 MA 6621 BP 1194 EP 1194 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CR3BL UT WOS:000361205108016 ER PT J AU Ovaska, MT Madanat, R Honkamaa, M Makinen, TJ AF Ovaska, Mikko T. Madanat, Rami Honkamaa, Maija Maekinen, Tatu J. TI Contemporary demographics and complications of patients treated for open ankle fractures SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE Open ankle fracture; Demographic; Complication; Deep infection; Wound necrosis ID INTERNAL-FIXATION; OPEN REDUCTION; SOFT-TISSUE; DEBRIDEMENT; INFECTION; MANAGEMENT; SURGERY; TIME AB Open ankle fractures are rare injuries with a high likelihood of wound complications and subsequent infections. There is limited information about the complications and outcomes of these injuries in different age groups. The aim of this study was to assess the contemporary demographics and complications related to this injury. We performed a chart review of all the 3030 patients treated for ankle fractures at a Level 1 trauma centre from 2006 to 2011.137 (4.5%) patients had an open ankle fracture. The demographic data, injury mechanism, comorbidities, and fracture type were collected. Treatment, complications, length of stay and number of outpatient visits were also recorded. The mean age of the patients was 60 years and 56% were women. Most fractures were Weber type B with a medial sided wound (93%). Only 20% of the fractures were the result of high-energy trauma, and 31% were Gustilo grade III injuries. Immediate internal fixation was performed in 82% of patients, and the wound was primarily closed in most cases (80%). The incidence of postoperative wound necrosis and deep infection was 18% and 17%, respectively. There were more deep infections if pulsatile lavage was used during the wound debridement (p = 0.029). About 14 (10%) patients required a flap reconstruction to cover the soft-tissue defect. Every other patient (54%) had a complication, and 21 patients (15%) suffered a long-term disability related to the injury. The number complications did not differ for nighttime and daytime operations (p = 0.083). High-energy injuries were more common in younger patients (p < 0.001) and these patients also had more lateral sided open wounds than older patients (p = 0.002). Interestingly, younger patients also had significantly more complications (p = 0.024), suffered more often from chronic pain (p = 0.003), and required more flap reconstructions (p = 0.026), reoperations (p = 0.026), and outpatient clinic visits (p = 0.006). Open ankle fractures have a high complication rate and often require multiple surgical procedures. In young patients these injuries are more likely to be the consequence of high-energy trauma leading to more complications and subsequently increased healthcare resource utilisation. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Ovaska, Mikko T.; Honkamaa, Maija] Univ Helsinki, Cent Hosp, Dept Orthopaed & Traumatol, SF-00260 Helsinki, Finland. [Madanat, Rami] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Madanat, Rami] Harvard Univ, Sch Med, Boston, MA USA. [Maekinen, Tatu J.] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Maekinen, Tatu J.] Univ Toronto, Toronto, ON, Canada. RP Ovaska, MT (reprint author), Univ Helsinki, Cent Hosp, Dept Orthopaed & Traumatol, Topeliuksenkatu 5, SF-00260 Helsinki, Finland. EM mikko.ovaska@hus.fi FU HUS EVO; Jane and Aatos Erkko Foundation; Paulo Foundation; Finnish Medical Foundation FX This study was supported by grants from the HUS EVO, the Jane and Aatos Erkko Foundation, the Paulo Foundation, and the Finnish Medical Foundation. NR 24 TC 8 Z9 8 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 EI 1879-0267 J9 INJURY JI Injury-Int. J. Care Inj. PD AUG PY 2015 VL 46 IS 8 BP 1650 EP 1655 DI 10.1016/j.injury.2015.04.015 PG 6 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA CS2IR UT WOS:000361894200040 PM 25935358 ER PT J AU Gupta, MP Lane, AM DeAngelis, MM Mayne, K Crabtree, M Gragoudas, ES Kim, IK AF Gupta, Mrinali P. Lane, Anne Marie DeAngelis, Margaret M. Mayne, Katie Crabtree, Margaux Gragoudas, Evangelos S. Kim, Ivana K. TI Clinical Characteristics of Uveal Melanoma in Patients With Germline BAP1 Mutations SO JAMA OPHTHALMOLOGY LA English DT Article ID ONCOGENIC MUTATIONS; IMMUNOHISTOCHEMISTRY; ENUCLEATION; METASTASIS; PREDICTION; PROGNOSIS; SURVIVAL; GNAQ AB IMPORTANCE Somatic mutations in BAP1 (BRCA1-associated protein 1 gene) are frequently identified in uveal melanoma. To date, the role of germline BAP1 mutations in uveal melanoma has not been characterized. OBJECTIVE To characterize the clinical phenotype of uveal melanoma in patients with germline BAP1 mutations. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study at an academic ophthalmology referral center among 507 patients with uveal melanoma who consented for collection of blood samples. The study dates were June 22, 1992, to December 14, 2010. MAIN OUTCOMES AND MEASURES Clinical characteristics of uveal melanoma and the development of metastases. BAP1 gene sequencing from blood samples of patients with uveal melanoma was correlated with clinical characteristics. RESULTS Of 507 blood samples analyzed, 25 patients (4.9%) exhibited 18 BAP1 polymorphisms, of which 9 were novel. Computational analyses predicted that 8 BAP1 mutations in 8 patients (1.6%) were likely to result in damaged BAP1 protein. Five of these 8 mutations were novel. These 8 patients were compared with 482 patients in whom no BAP1 polymorphisms were identified. In univariate analyses, patients with germline BAP1 mutations exhibited larger tumor diameters (mean, 15.9 vs 12.3 mm; P = .004) and higher rates of ciliary body involvement (75.0% vs 21.6%, P = .002) and metastases (71.4% vs 18.0%, P = .003) compared with control subjects. Patients with germline BAP1 mutations exhibited increased frequency of family history of cancer (100% vs 65.9%, P = .06), particularly cutaneous melanoma (62.5% vs 9.9%, P < .001) and ocular melanoma (25.0% vs 1.9%, P = .01). No differences were identified in age at diagnosis, sex, history of other malignant neoplasm, presenting visual acuity, distance of the tumor from the optic nerve or fovea, iris involvement, extrascleral extension, or tumor pigmentation. Germline BAP1 mutations increased risk of metastasis independent of ciliary body involvement (P = .02). Germline BAP1 mutation approached significance as an independent risk factor for metastasis (P = .09). CONCLUSIONS AND RELEVANCE These data suggest that germline BAP1 mutations occur infrequently in uveal melanoma and are associated with larger tumors and higher rates of ciliary body involvement, 2 known risk factors for metastasis. C1 [Gupta, Mrinali P.; Lane, Anne Marie; Gragoudas, Evangelos S.; Kim, Ivana K.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Gupta, Mrinali P.] Weill Cornell Med Coll, New York, NY USA. [DeAngelis, Margaret M.; Mayne, Katie; Crabtree, Margaux] Univ Utah, Dept Ophthalmol, Salt Lake City, UT USA. RP Kim, IK (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM ivana_kim@meei.harvard.edu RI DeAngelis, e/J-7863-2015 FU Grimshaw-Gudewicz Charitable Foundation FX This study was supported by funding from the Grimshaw-Gudewicz Charitable Foundation. NR 36 TC 10 Z9 10 U1 0 U2 3 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 2015 VL 133 IS 8 BP 881 EP 887 DI 10.1001/jamaophthalmol.2015.1119 PG 7 WC Ophthalmology SC Ophthalmology GA CR5IP UT WOS:000361374800008 PM 25974357 ER PT J AU Aiello, LP Ayala, AR Antoszyk, AN Arnold-Bush, B Baker, C Bressler, NM Elman, MJ Glassman, AR Jampol, LM Melia, M Nielsen, J Wolpert, HA AF Aiello, Lloyd Paul Ayala, Allison R. Antoszyk, Andrew N. Arnold-Bush, Bambi Baker, Carl Bressler, Neil M. Elman, Michael J. Glassman, Adam R. Jampol, Lee M. Melia, Michele Nielsen, Jared Wolpert, Howard A. CA Diabetic Retinopathy Clinical Res TI Assessing the Effect of Personalized Diabetes Risk Assessments During Ophthalmologic Visits on Glycemic Control A Randomized Clinical Trial SO JAMA OPHTHALMOLOGY LA English DT Article ID COMPLICATIONS TRIAL; RETINOPATHY; ADOLESCENTS; PROGRESSION AB IMPORTANCE Optimization of glycemic control is critical to reduce the number of diabetes mellitus-related complications, but long-term success is challenging. Although vision loss is among the greatest fears of individuals with diabetes, comprehensive personalized diabetes education and risk assessments are not consistently used in ophthalmologic settings. OBJECTIVE To determine whether the point-of-care measurement of hemoglobin A(1c) (HbA(1c)) and personalized diabetes risk assessments performed during retinal ophthalmologic visits improve glycemic control as assessed by HbA1c level. DESIGN, SETTING, AND PARTICIPANTS Ophthalmologist office-based randomized, multicenter clinical trial in which investigators from 42 sites were randomly assigned to provide either a study-prescribed augmented diabetes assessment and education or the usual care. Adults with type 1 or 2 diabetes enrolled into 2 cohorts: those with a more-frequent-than-annual follow-up (502 control participants and 488 intervention participants) and those with an annual follow-up (368 control participants and 388 intervention participants). Enrollment was from April 2011 through January 2013. INTERVENTIONS Point-of-care measurements of HbA1c, blood pressure, and retinopathy severity; an individualized estimate of the risk of retinopathy progression derived from the findings from ophthalmologic visits; structured comparison and review of past and current clinical findings; and structured education with immediate assessment and feedback regarding participant's understanding. These interventions were performed at enrollment and at routine ophthalmic follow-up visits scheduled at least 12 weeks apart. MAIN OUTCOMES AND MEASURES Mean change in HbA1c level from baseline to 1-year follow-up. Secondary outcomes included body mass index, blood pressure, and responses to diabetes self-management practices and attitudes surveys. RESULTS In the cohort with more-frequent-than-annual follow-ups, the mean (SD) change in HbA1c level at 1 year was -0.1% (1.5%) in the control group and -0.3%(1.4%) in the intervention group (adjusted mean difference, -0.09% [95% CI, -0.29% to 0.12%]; P = .35). In the cohort with annual follow-ups, the mean (SD) change in HbA1c level was 0.0% (1.1%) in the control group and -0.1%(1.6%) in the intervention group (mean difference, -0.05% [95% CI, -0.27% to 0.18%]; P = .63). Results were similar for all secondary outcomes. CONCLUSIONS AND RELEVANCE Long-term optimization of glycemic control is not achieved by a majority of individuals with diabetes. The addition of personalized education and risk assessment during retinal ophthalmologic visits did not result in a reduction in HbA1c level compared with usual care over 1 year. These data suggest that optimizing glycemic control remains a substantive challenge requiring interventional paradigms other than those examined in our study. C1 [Aiello, Lloyd Paul] Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst,Dept Ophthalmol, Boston, MA 02115 USA. [Ayala, Allison R.; Arnold-Bush, Bambi; Glassman, Adam R.; Melia, Michele] Jaeb Ctr Hlth Res, Tampa, FL 33647 USA. [Antoszyk, Andrew N.] Charlotte Eye Ear Nose & Throat Associates, Charlotte, NC USA. [Baker, Carl] Paducah Retinal Ctr, Paducah, KY USA. [Bressler, Neil M.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. [Elman, Michael J.] Elman Retina Grp, Baltimore, MD USA. [Jampol, Lee M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Nielsen, Jared] Wolfe Eye Clin, W Des Moines, IA USA. [Wolpert, Howard A.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Adult Diabet,Dept Med, Boston, MA 02115 USA. RP Ayala, AR (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Ste 350, Tampa, FL 33647 USA. EM drcrstat1@jaeb.org FU National Eye Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health; US Department of Health and Human Services [EY14231, EY23207, EY18817] FX This work was supported by a cooperative agreement from the National Eye Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Health, and the US Department of Health and Human Services (grants EY14231, EY23207, and EY18817). NR 22 TC 9 Z9 9 U1 2 U2 3 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 2015 VL 133 IS 8 BP 888 EP 896 DI 10.1001/jamaophthalmol.2015.1312 PG 9 WC Ophthalmology SC Ophthalmology GA CR5IP UT WOS:000361374800009 PM 25996273 ER PT J AU Brugge, WR AF Brugge, William R. TI Diagnosis and management of cystic lesions of the pancreas SO JOURNAL OF GASTROINTESTINAL ONCOLOGY LA English DT Review DE Pancreas; cystic lesions; pseudocyst; mucinous cyst; intraductal papillary mucinous neoplasms (IPMNs); endoscopic ultrasonography (endoscopic US) ID PAPILLARY MUCINOUS NEOPLASMS; FINE-NEEDLE-ASPIRATION; SOLID PSEUDOPAPILLARY NEOPLASM; OVARIAN-TYPE STROMA; CLINICOPATHOLOGICAL FEATURES; PREOPERATIVE DIAGNOSIS; SEROUS CYSTADENOMA; PSEUDOCYSTS; TUMORS; EUS AB Pancreatic cystic lesions (PCLs) are being increasingly identified in recent years. They show a wide spectrum of imaging and clinical features. The diagnosis and discrimination of these lesions are very important because of the risk for concurrent or later development of malignancy. PCLs are usually first diagnosed and characterized by conventional imaging modalities such as trans-abdominal ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI). However, their ability to differentiate the benign and malignant lesions remains limited. Endoscopic US may be more helpful for the diagnosis and differentiation of PCLs because of its high resolution and better imaging characteristics than cross-sectional imaging modalities. It also allows for fine-needle aspiration (FNA) of cystic lesions for biochemical, cytological and DNA analysis that might be further helpful for diagnosis and differentiation. The management options of PCLs are to observe, endoscopic treatment or surgical resection. However, the decision for management is sometimes hampered by limitations in current diagnostic and tissue sampling techniques. As further diagnostic and non-invasive management options become available, clinical decision-making will become much easier for these lesions. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM wbrugge@partners.org NR 60 TC 7 Z9 7 U1 1 U2 6 PU PIONEER BIOSCIENCE PUBL CO PI HONG KONG PA 9A GOLD SHINE TOWER, 346-348 QUEEN'S RD CENTRAL, SHEUNG WAN, HONG KONG, 00000, PEOPLES R CHINA SN 2078-6891 EI 2219-679X J9 J GASTROINTEST ONCOL JI J. Gastrointest. Oncol. PD AUG PY 2015 VL 6 IS 4 BP 375 EP 388 DI 10.3978/j.issn.2078-6891.2015.057 PG 14 WC Oncology SC Oncology GA CS4ZC UT WOS:000362083900004 PM 26261724 ER PT J AU Pal, S Azad, A Bhatia, S Drabkin, H Costello, B Sarantopoulos, J Kanesvaran, R Lauer, R Starodub, A Hauke, R Sweeney, CJ Hahn, NM Sonpavde, G Richey, S Breen, T Kremmidiotis, G Leske, A Doolin, E Bibby, DC Simpson, J Iglesias, J Hutson, T AF Pal, Sumanta Azad, Arun Bhatia, Shailender Drabkin, Harry Costello, Brian Sarantopoulos, John Kanesvaran, Ravindran Lauer, Richard Starodub, Alexander Hauke, Ralph Sweeney, Christopher J. Hahn, Noah M. Sonpavde, Guru Richey, Stephen Breen, Timothy Kremmidiotis, Gabriel Leske, Annabell Doolin, Elizabeth Bibby, David C. Simpson, Jeremy Iglesias, Jose Hutson, Thomas TI A Phase I/II Trial of BNC105P with Everolimus in Metastatic Renal Cell Carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID MICROVESSEL DENSITY; III TRIAL; CANCER; EXPRESSION; INHIBITOR; ANGIOGENESIS; SORAFENIB; CORRELATE; EFFICACY; PROTEIN AB Purpose: BNC105P inhibits tubulin polymerization, and preclinical studies suggest possible synergy with everolimus. In this phase I/II study, efficacy and safety of the combination were explored in patients with metastatic renal cell carcinoma (mRCC). Experimental Design: A phase I study in patients with clear cell mRCC and any prior number of therapies was conducted using a classical 3 + 3 design to evaluate standard doses of everolimus with increasing doses of BNC105P. At the recommended phase II dose (RP2D), patients with clear cell mRCC and one to two prior therapies (including >= 1 VEGF-TKI) were randomized to BNC105P with everolimus (arm A) or everolimus alone (arm B). The primary endpoint of the study was 6-month progression-free survival (6MPFS). Secondary endpoints included response rate, PFS, overall survival, and exploratory biomarker analyses. Results: In the phase I study (N = 15), a dose of BNC105P at 16 mg/m(2) with everolimus at 10mg daily was identified as the RP2D. In the phase II study, 139 patients were randomized, with 69 and 67 evaluable patients in arms A and B, respectively. 6MPFS was similar in the treatment arms (arm A: 33.82% vs. arm B: 30.30%, P = 0.66) and no difference in median PFS was observed (arm A: 4.7 mos vs. arm B: 4.1 mos; P = 0.49). Changes in matrix metalloproteinase-9, stem cell factor, sex hormone-binding globulin, and serum amyloid A protein were associated with clinical outcome with BNC105P. Conclusions: Although the primary endpoint was not met in an unselected population, correlative studies suggest several biomarkers that warrant further prospective evaluation. (C) 2015 AACR. C1 [Pal, Sumanta] City Hope Med Ctr, Duarte, CA USA. [Azad, Arun] BC Canc Agcy, Vancouver, BC, Canada. [Bhatia, Shailender] Univ Washington, Seattle, WA 98195 USA. [Drabkin, Harry] Med Univ S Carolina, Charleston, SC 29425 USA. [Costello, Brian] Mayo Clin, Rochester, MN USA. [Sarantopoulos, John] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Kanesvaran, Ravindran] Natl Canc Ctr, Singapore, Singapore. [Lauer, Richard] Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA. [Starodub, Alexander] Indiana Univ, Hlth Goshen Ctr Canc Care, Goshen, IN USA. [Hauke, Ralph] Nebraska Canc Specialists, Nebraska Methodist Hosp, Omaha, NE USA. [Sweeney, Christopher J.] Dana Farber Canc Ctr, Boston, MA USA. [Hahn, Noah M.] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Sonpavde, Guru] Univ Alabama Birmingham, Birmingham, AL USA. [Richey, Stephen] Texas Oncol, Ft Worth, TX USA. [Breen, Timothy] Hoosier Canc Res Network, Indianapolis, IN USA. [Kremmidiotis, Gabriel; Leske, Annabell; Doolin, Elizabeth; Bibby, David C.; Simpson, Jeremy; Iglesias, Jose] Bionomics, Thebarton, SA, Australia. [Hutson, Thomas] Baylor Univ, Med Ctr, Charles A Sammons Canc Ctr, Dallas, TX USA. RP Pal, S (reprint author), City Hope Comprehens Canc Ctr, 1500 East,Duarte Rd, Duarte, CA 91010 USA. EM spal@coh.org FU NCI NIH HHS [P30 CA006973, P30 CA015704] NR 24 TC 4 Z9 4 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 1 PY 2015 VL 21 IS 15 BP 3420 EP 3427 DI 10.1158/1078-0432.CCR-14-3370 PG 8 WC Oncology SC Oncology GA CS2NK UT WOS:000361907800010 PM 25788492 ER PT J AU Smith, CG Fisher, D Harris, R Maughan, TS Phipps, AI Richman, S Seymour, M Tomlinson, I Rosmarin, D Kerr, D Chan, AT Peters, U Newcomb, PA Idziaszczyk, S West, H Meade, A Kaplan, R Cheadle, JP AF Smith, Christopher G. Fisher, David Harris, Rebecca Maughan, Timothy S. Phipps, Amanda I. Richman, Susan Seymour, Matthew Tomlinson, Ian Rosmarin, Dan Kerr, David Chan, Andrew T. Peters, Ulrike Newcomb, Polly A. Idziaszczyk, Shelley West, Hannah Meade, Angela Kaplan, Richard Cheadle, Jeremy P. TI Analyses of 7,635 Patients with Colorectal Cancer Using Independent Training and Validation Cohorts Show That rs9929218 in CDH1 Is a Prognostic Marker of Survival SO CLINICAL CANCER RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; SINGLE NUCLEOTIDE POLYMORPHISM; COMMON GENETIC-VARIANTS; SUSCEPTIBILITY LOCI; MICROSATELLITE INSTABILITY; RISK; METAANALYSIS; CHEMOTHERAPY; DIAGNOSIS; CETUXIMAB AB Purpose: Genome-wide association studies have identified numerous loci associated with colorectal cancer risk. Several of these have also been associated with patient survival, although none have been validated. Here, we used large independent training and validation cohorts to identify robust prognostic biomarkers for colorectal cancer. Experimental Design: In our training phase, we analyzed 20 colorectal cancer-risk SNPs from 14 genome-wide associated loci, for their effects on survival in 2,083 patients with advanced colorectal cancer. A Cox survival model was used, stratified for treatment, adjusted for known prognostic factors, and corrected for multiple testing. Three SNPs were subsequently analyzed in an independent validation cohort of 5,552 colorectal cancer patients. A validated SNP was analyzed by disease stage and response to treatment. Results: Three variants associated with survival in the training phase; however, only rs9929218 at 16q22 (intron 2 of CDH1, encoding E-cadherin) was significant in the validation phase. Patients homozygous for the minor allele (AA genotype) had worse survival (training phase HR, 1.43; 95% confidence intervals; CI, 1.20-1.71, P = 5.8 x 10 (-5); validation phase HR, 1.18; 95% CI, 1.01-1.37, P = 3.2 x 10(-2); combined HR, 1.28; 95% CI, 1.14-1.43, P = 2.2 x 10(-5)). This effect was independent of known prognostic factors, and was significant amongst patients with stage IV disease (P = 2.7 x 10(-5)). rs9929218 was also associated with poor response to chemotherapy (P = 3.9 x 10(-4)). Conclusions: We demonstrate the potential of common inherited genetic variants to inform patient outcome and show that rs9929218 identifies approximately 8% of colorectal cancer patients with poor prognosis. rs9929218 may affect CDH1 expression and E-cadherin plays a role in epithelial-to-mesenchymal transition providing a mechanism underlying its prognostic potential. (C) 2015 AACR. C1 [Smith, Christopher G.; Harris, Rebecca; Idziaszczyk, Shelley; West, Hannah; Cheadle, Jeremy P.] Cardiff Univ, Inst Canc & Genet, Sch Med, Cardiff CF14 4XN, S Glam, Wales. [Fisher, David; Meade, Angela; Kaplan, Richard] MRC Clin Trials Unit, London, England. [Maughan, Timothy S.] Univ Oxford, MRC Oxford Inst Radiat Oncol, CRUK, Oxford, England. [Phipps, Amanda I.; Peters, Ulrike; Newcomb, Polly A.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Phipps, Amanda I.; Peters, Ulrike; Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Richman, Susan; Seymour, Matthew] Univ Leeds, St James Univ Hosp, Leeds, W Yorkshire, England. [Tomlinson, Ian; Rosmarin, Dan] Univ Oxford, Wellcome Trust Ctr Human Genet, Mol & Populat Genet Lab, Oxford, England. [Tomlinson, Ian; Rosmarin, Dan] Univ Oxford, Wellcome Trust Ctr Human Genet, NIHR Comprehens Biomed Res Ctr, Oxford, England. [Kerr, David] Univ Oxford, Nuffield Dept Clin Lab Sci, Oxford, England. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Chan, Andrew T.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. RP Cheadle, JP (reprint author), Cardiff Univ, Inst Canc & Genet, Sch Med, Heath Pk, Cardiff CF14 4XN, S Glam, Wales. EM cheadlejp@cardiff.ac.uk FU Cancer Research UK; Medical Research Council; Tenovus; Kidani Trust; Cancer Research Wales; National Institute for Social Care and Health Research Cancer Genetics Biomedical Research Unit; Medical Research Council [ISRCTN21221452]; Cancer Research UK [ISRCTN21221452, ISRCTN93248876]; Amgen; Wellcome Trust [090532/Z/09/Z]; National Cancer Institute (NCI), National Institutes of Health (NIH); U.S. Department of Health and Human Services (DHHS) [U01 CA137088, R01 CA059045]; HPFS [P01 CA055075, UM1 CA167552, R01 CA137178, P50 CA127003]; NHS [R01 CA137178, P50 CA127003, P01 CA087969]; PHS [R01 CA042182]; VITAL [K05 CA154337]; Intramural Research Program of the Division of Cancer Epidemiology and Genetics; Division of Cancer Prevention, NCI, NIH; DHHS [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; National Heart, Lung and Blood Institute, NIH FX COIN and COINB were funded by Cancer Research UK and the Medical Research Council, and the associated translational studies were supported by the Bobby Moore Fund from Cancer Research UK, Tenovus, the Kidani Trust, Cancer Research Wales and the National Institute for Social Care and Health Research Cancer Genetics Biomedical Research Unit (2011-2015). FOCUS2 (ISRCTN21221452) was funded jointly by the Medical Research Council and Cancer Research UK. PICCOLO (ISRCTN93248876) was funded by Cancer Research UK, with support from Amgen. FOCUS3 was funded by the Medical Research Council Efficacy and Mechanism Evaluation Programme. Core funding to the Wellcome Trust Centre for Human Genetics was provided by the Wellcome Trust (grant 090532/Z/09/Z). GECCO was supported by the National Cancer Institute (NCI), National Institutes of Health (NIH), and U.S. Department of Health and Human Services (DHHS; U01 CA137088 and R01 CA059045). NIH also supported HPFS (P01 CA055075, UM1 CA167552, R01 CA137178 and P50 CA127003), NHS (R01 CA137178, P01 CA087969 and P50 CA127003), PHS (R01 CA042182), and VITAL (K05 CA154337). PLCO was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, and supported by contracts from the Division of Cancer Prevention, NCI, NIH, and DHHS. WHI was supported by the National Heart, Lung and Blood Institute, NIH, and DHHS (HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C). NR 43 TC 0 Z9 0 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 1 PY 2015 VL 21 IS 15 BP 3453 EP 3461 DI 10.1158/1078-0432.CCR-14-3136 PG 9 WC Oncology SC Oncology GA CS2NK UT WOS:000361907800014 PM 25873087 ER PT J AU Papafaklis, MI Bourantas, CV Yonetsu, T Vergallo, R Kotsia, A Nakatani, S Lakkas, LS Athanasiou, LS Naka, KK Fotiadis, DI Feldman, CL Stone, PH Serruys, PW Jang, IK Michalis, LK AF Papafaklis, Michail I. Bourantas, Christos V. Yonetsu, Taishi Vergallo, Rocco Kotsia, Anna Nakatani, Shimpei Lakkas, Lampros S. Athanasiou, Lambros S. Naka, Katerina K. Fotiadis, Dimitrios I. Feldman, Charles L. Stone, Peter H. Serruys, Patrick W. Jang, Ik-Kyung Michalis, Lampros K. TI Anatomically correct three-dimensional coronary artery reconstruction using frequency domain optical coherence tomographic and angiographic data: head-to-head comparison with intravascular ultrasound for endothelial shear stress assessment in humans SO EUROINTERVENTION LA English DT Article DE angiography; endothelial shear stress; intravascular ultrasound; optical coherence tomography; three-dimensional reconstruction ID IN-VIVO; DIMENSIONS; VALIDATION; FUSION AB Aims: To develop a methodology that permits accurate 3-dimensional (3D) reconstruction from FD-OCT and angiographic data enabling reliable evaluation of the ESS distribution, and to compare the FD-OCT-derived models against the established models based on angiography/IVUS. Methods and results: Fifteen patients (17 coronary arteries) who underwent angiography, FD-OCT and IVUS examination during the same procedure were studied. The FD-OCT and IVUS lumen borders were placed onto the 3D luminal centreline derived from angiographic data. Three-dimensional geometry algorithms and anatomical landmarks were used to estimate the orientation of the borders appropriately. ESS was calculated using computational fluid dynamics. In 188 corresponding consecutive 3-mm segments, FD-OCTand IVUS-derived models were highly correlated for lumen area (r=0.96) and local ESS (r=0.89) measurements. FD-OCT-based 3D reconstructions had a high diagnostic accuracy for detecting regions exposed to proatherogenic low ESS identified on the IVUS-based 3D models, considered as the gold standard (receiver operator characteristic area under the curve: 94.9%). Conclusions: FD-OCT-based 3D coronary reconstruction provides anatomically correct models and permits reliable ESS computation. ESS assessment in combination with the superior definition of plaque characteristics by FD-OCT is expected to provide valuable insights into the effect of the haemodynamic environment on the development and destabilisation of high-risk plaques. C1 [Papafaklis, Michail I.; Feldman, Charles L.; Stone, Peter H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. [Papafaklis, Michail I.; Kotsia, Anna; Lakkas, Lampros S.; Naka, Katerina K.; Michalis, Lampros K.] Univ Ioannina, Sch Med, Dept Cardiol, GR-45110 Ioannina, Greece. [Bourantas, Christos V.; Nakatani, Shimpei; Serruys, Patrick W.] Erasmus MC, Thoraxctr, Rotterdam, Netherlands. [Yonetsu, Taishi; Vergallo, Rocco; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Athanasiou, Lambros S.; Fotiadis, Dimitrios I.] Univ Ioannina, Dept Mat Sci & Engn, GR-45110 Ioannina, Greece. RP Michalis, LK (reprint author), Univ Ioannina, Sch Med, Dept Cardiol, POB 1186, GR-45110 Ioannina, Greece. EM lmihalis@cc.uoi.gr OI Papafaklis, Michail/0000-0002-5646-0378 FU George D. Behrakis Fellowship; Hellenic Heart Foundation FX We acknowledge the support of the George D. Behrakis Fellowship and the Hellenic Heart Foundation. We thank Michelle Lucier, BSc, for technical evaluation of IVUS images. NR 19 TC 8 Z9 8 U1 0 U2 5 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 2015 VL 11 IS 4 BP 407 EP 415 DI 10.4244/EIJY14M06_11 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CS1UM UT WOS:000361853800009 PM 24974809 ER PT J AU Kvale, EA Meneses, K Demark-Wahnefried, W Bakitas, M Ritchie, C AF Kvale, Elizabeth A. Meneses, Karen Demark-Wahnefried, Wendy Bakitas, Marie Ritchie, Christine TI Formative research in the development of a care transition intervention in breast cancer survivors SO EUROPEAN JOURNAL OF ONCOLOGY NURSING LA English DT Article DE Breast cancer; Survivorship; Transitional care; Self-management; Qualitative research ID QUALITY-OF-LIFE; SELF-MANAGEMENT; LONG-TERM; PHYSICAL-ACTIVITY; HEALTH BEHAVIORS; CHRONIC ILLNESS; CHRONIC DISEASE; PROJECT LEAD; OUTCOMES; SUPPORT AB Purpose: The purpose of this qualitative study was to evaluate breast cancer survivors' (BCS) responses to a self-management survivorship care transition intervention in the formative development of such an intervention. The experience of BCS is marked by uncertainty and anxiety about subsequent care, and a desire for more information about future care needs and late effects of treatment. Self-management strategies have demonstrated improved outcomes in chronic illness, and may address the unmet needs of breast cancer survivors. Methods and Sample: Five focus and discussion groups each were conducted at a single site in the Southeastern United States with a total of twenty breast cancer survivors. BCS were presented with a description of a survivorship transition intervention that encouraged self-management. Groups were led by a trained moderator using a semi-structured guide with 7 open-ended questions about their care transition experience and response to the proposed intervention. A theoretically-derived, concept-guided coding strategy was developed after review of transcripts. Iterative constant comparative methods were used to ensure that transcripts were reviewed exhaustively for emerging codes and relationships. Key results: Three dominant themes emerged around readiness for self-management: 1) the breast cancer experience as a catalyst for self-management; 2) fear of recurrence as a catalyst for self-management; and 3) the impact of the meaning of breast cancer on individual readiness for self-management. Conclusions: These findings contribute to further development of a conceptual model and interventions built on BCS self-management to improve the survivorship experience. Published by Elsevier Ltd. C1 [Kvale, Elizabeth A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Kvale, Elizabeth A.; Meneses, Karen; Demark-Wahnefried, Wendy; Bakitas, Marie] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Bakitas, Marie] Univ Alabama Birmingham, Sch Nursing, Birmingham, AL 35294 USA. [Ritchie, Christine] San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Ritchie, Christine] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Kvale, EA (reprint author), CH19 Room 219R, Birmingham, AL 35294 USA. EM ekvale@uabmc.edu OI Demark-Wahnefried, Wendy/0000-0001-5241-932X; Meneses, Karen/0000-0002-6094-2230; Bakitas, Marie/0000-0002-2913-2053 FU American Cancer Society [121093-CCCDA-11-191-01-CCCDA] FX Supported by Cancer Control Career Development Award for Primary Care Physicians (grant number 121093-CCCDA-11-191-01-CCCDA) from the American Cancer Society. The sponsor had no role in the study design, in the collection, analysis and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication. NR 40 TC 3 Z9 3 U1 2 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1462-3889 EI 1532-2122 J9 EUR J ONCOL NURS JI Eur. J. Oncol. Nurs. PD AUG PY 2015 VL 19 IS 4 BP 329 EP 335 DI 10.1016/j.ejon.2015.01.010 PG 7 WC Oncology; Nursing SC Oncology; Nursing GA CR5RV UT WOS:000361402500001 PM 25726359 ER PT J AU Ng, K Chan, AT Fuchs, CS AF Ng, Kimmie Chan, Andrew T. Fuchs, Charles S. TI RE: Aspirin and COX-2 Inhibitor Use in Patients With Stage III Colon Cancer Response SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID PREVENT COLORECTAL ADENOMAS; RANDOMIZED-TRIAL C1 [Ng, Kimmie; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. RP Ng, K (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM kimmie_ng@dfci.harvard.edu NR 6 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 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD AUG PY 2015 VL 107 IS 8 AR djv150 DI 10.1093/jnci/djv150 PG 1 WC Oncology SC Oncology GA CS1OP UT WOS:000361836400015 ER PT J AU Nipp, RD Ryan, DP AF Nipp, Ryan D. Ryan, David P. TI Predicting a Response to FOLFIRINOX in Pancreatic Cancer SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID ADENOCARCINOMA; GEMCITABINE; TUMOR C1 [Nipp, Ryan D.; Ryan, David P.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Nipp, RD (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA. EM rnipp@partners.org NR 12 TC 0 Z9 0 U1 2 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 2015 VL 107 IS 8 AR djv175 DI 10.1093/jnci/djv175 PG 2 WC Oncology SC Oncology GA CS1OP UT WOS:000361836400020 ER PT J AU Serrano, C Wang, YX Marino-Enriquez, A Lee, JC Ravegnini, G Morgan, JA Bertagnolli, MM Beadling, C Demetri, GD Corless, CL Heinrich, MC Fletcher, JA AF Serrano, Cesar Wang, Yuexiang Marino-Enriquez, Adrian Lee, Jen-Chieh Ravegnini, Gloria Morgan, Jeffrey A. Bertagnolli, Monica M. Beadling, Carol Demetri, George D. Corless, Christopher L. Heinrich, Michael C. Fletcher, Jonathan A. TI KRAS and KIT Gatekeeper Mutations Confer Polyclonal Primary Imatinib Resistance in GI Stromal Tumors: Relevance of Concomitant Phosphatidylinositol 3-Kinase/AKT Dysregulation SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID V600E BRAF MUTATIONS; SUCCINATE-DEHYDROGENASE; PATHWAY; MECHANISMS; INHIBITORS; CANCERS C1 [Serrano, Cesar; Wang, Yuexiang; Marino-Enriquez, Adrian; Lee, Jen-Chieh; Ravegnini, Gloria; Bertagnolli, Monica M.; Fletcher, Jonathan A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Serrano, Cesar; Morgan, Jeffrey A.; Demetri, George D.; Fletcher, Jonathan A.] Dana Farber Canc Inst, Ludwig Ctr, Boston, MA 02115 USA. [Serrano, Cesar; Morgan, Jeffrey A.; Demetri, George D.; Fletcher, Jonathan A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Lee, Jen-Chieh] Natl Taiwan Univ, Natl Taiwan Univ Hosp, Coll Med, Taipei 10764, Taiwan. [Ravegnini, Gloria] Univ Bologna, Bologna, Italy. [Beadling, Carol; Heinrich, Michael C.] Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. [Beadling, Carol; Corless, Christopher L.; Heinrich, Michael C.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. RP Serrano, C (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM jfletcher@partners.org RI RAVEGNINI, GLORIA/K-1330-2016; OI RAVEGNINI, GLORIA/0000-0002-7774-402X; Lee, Jen-Chieh/0000-0001-7739-5934 FU GI Specialized Program of Research Excellence [1P50CA12703-05]; Virginia and Daniel K. Ludwig Trust for Cancer Research; GI Stromal Tumor (GIST) Cancer Research Fund; Life Raft Group; B.P. Lester Foundation; Veterans Affairs Merit Review Grant from the Department of Veterans' Affairs; Cesarini Pan Mass Challenge for GIST; Italian Society of Pharmacology and Fondazione del Monte di Bologna e Ravenna; Sarcoma Alliance for Research through Collaboration; Spanish Society of Medical Oncology FX This work was supported by GI Specialized Program of Research Excellence Grant No. 1P50CA12703-05 (J.A.F., G.D.D.), grants from the Virginia and Daniel K. Ludwig Trust for Cancer Research (J.A.F., G.D.D.), the GI Stromal Tumor (GIST) Cancer Research Fund (C.L.C., M.C.H., J.A.F.), the Life Raft Group (C.L.C., M.C.H., J.A.F.), the B.P. Lester Foundation (C.L.C., M.C.H.), a Veterans Affairs Merit Review Grant from the Department of Veterans' Affairs (M.C.H.), the Cesarini Pan Mass Challenge for GIST (J.A.F., G.D.D.), the Italian Society of Pharmacology and Fondazione del Monte di Bologna e Ravenna (G.R.), the Sarcoma Alliance for Research through Collaboration (A.M.E.), and the Spanish Society of Medical Oncology (C.S.). Both C.S. and Y.W. contributed equally to this work. NR 16 TC 6 Z9 6 U1 1 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 1 PY 2015 VL 33 IS 22 BP E93 EP E96 DI 10.1200/JCO.2013.48.7488 PG 4 WC Oncology SC Oncology GA CR9DT UT WOS:000361654100001 PM 24687822 ER PT J AU Papakostas, GI Shelton, RC Henry, ME Bilello, JA AF Papakostas, George I. Shelton, Richard C. Henry, Michael E. Bilello, John A. TI Reply to Commentary by Rothschild: "A Blood Test for Depression?" SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Letter ID FIELD TRIALS; DSM-5 C1 [Papakostas, George I.; Henry, Michael E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Shelton, Richard C.] Univ Alabama Birmingham, Dept Psychiat, Birmingham, AL USA. [Bilello, John A.] Ridge Diagnost Inc, Res & Dev, Res Triangle Pk, NC USA. RP Papakostas, GI (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM gpapakostas@partners.org FU Ridge Diagnostics, Inc. FX The study discussed in this letter was supported by Ridge Diagnostics, Inc. NR 4 TC 0 Z9 0 U1 1 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD AUG PY 2015 VL 76 IS 8 BP E1038 EP E1038 DI 10.4088/JCP.15lr10018 PG 1 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CR8IE UT WOS:000361593800009 PM 26335092 ER PT J AU Maung, AA Toevs, CC Kayser, JB Kaplan, LJ AF Maung, Adrian A. Toevs, Christine C. Kayser, Joshua B. Kaplan, Lewis J. TI Conflict management teams in the intensive care unit: A concise definitive review SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Review ID OF-LIFE-CARE; PALLIATIVE CARE; ETHICS-CONSULTATION; END; ICU; COMMUNICATION; CHALLENGES; RESOLUTION; SOCIETY; QUALITY C1 [Maung, Adrian A.] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Toevs, Christine C.] Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. [Kayser, Joshua B.; Kaplan, Lewis J.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Maung, AA (reprint author), Yale Univ, Sch Med, Dept Surg, Sect Trauma Surg Crit Care & Surg Emergencies, 330 Cedar St,BB310, New Haven, CT 06520 USA. EM Adrian.Maung@yale.edu NR 37 TC 1 Z9 1 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD AUG PY 2015 VL 79 IS 2 BP 314 EP 320 DI 10.1097/TA.0000000000000728 PG 7 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA CS2II UT WOS:000361892800023 PM 26218703 ER PT J AU Chu, S Boxer, R Madison, P Kleinman, L Skolarus, T Altman, L Bennett, C Shelton, J AF Chu, Stephanie Boxer, Richard Madison, Pauline Kleinman, Leonard Skolarus, Ted Altman, Lisa Bennett, Carol Shelton, Jeremy TI Veterans Affairs Telemedicine: Bringing Urologic Care to Remote Clinics SO UROLOGY LA English DT Article ID PATIENT SATISFACTION; UNITED-STATES; SERVICES; ACCESS; TELECONSULTATION; COMMUNICATION; CONSULTATIONS; SURGERY; IMPACT; LEVEL AB OBJECTIVE To report the use of telemedicine to deliver general urologic care to remote locations within the Veterans Affairs Greater Los Angeles Healthcare System. We describe the diagnoses managed, patient satisfaction, safety, and benefit to patients in terms of saved travel time and expense. METHODS We conducted a retrospective chart review examining care delivered through urology telemedicine clinics over a 6-month period. We examined the urologic conditions, patient satisfaction, and emergency department visits within 30 days of the visit. We estimated patient benefit by calculating travel distance and time and the saved travel-associated costs using Google Maps and US Census income data. RESULTS Ninety-seven unique telemedicine visits were conducted and a total of 171 urologic diseases were assessed. The most common conditions were lower urinary tract symptoms (35%), elevated prostate-specific antigen level (15%), and prostate cancer (14%). One patient was seen in the emergency department within 30 days with an unpreventable urologic complaint. Patient satisfaction was "very good" to "excellent" in 95% of cases, and 97% would refer another veteran to the urology telemedicine clinic. Patients saved an average of 277 travel miles, 290 minutes of travel time, $67 in travel expenses, and $126 in lost opportunity cost. CONCLUSION Telemedicine was successfully and safely used to evaluate and treat a wide range of urologic conditions within the Veterans Affairs Greater Los Angeles Healthcare System, and saves patients nearly 5 hours and up to $193 per visit. Further investigation of the potential of telemedicine for the delivery of urologic care in a cost-effective manner is warranted. (C) 2015 Elsevier Inc. C1 [Chu, Stephanie] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles, Los Angeles, CA USA. Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. Vet Affairs Ann Arbor, HSR&D Ctr Hlth Commun Res, Ann Arbor, MI USA. RP Chu, S (reprint author), Univ Calif Los Angeles, Dept Urol, 405 Hilgard Ave, Los Angeles, CA 90024 USA. EM sdchu@mednet.ucla.edu NR 30 TC 8 Z9 8 U1 1 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 2015 VL 86 IS 2 BP 255 EP 260 DI 10.1016/j.urology.2015.04.038 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA CS2MJ UT WOS:000361904800016 PM 26168998 ER PT J AU Chu, S Boxer, R Madison, P Kleinman, L Skolarus, T Altman, L Bennett, C Shelton, J AF Chu, Stephanie Boxer, Richard Madison, Pauline Kleinman, Leonard Skolarus, Ted Altman, Lisa Bennett, Carol Shelton, Jeremy TI Veterans Affairs Telemedicine: Bringing Urologic Care to Remote Clinics REPLY SO UROLOGY LA English DT Editorial Material C1 [Chu, Stephanie; Boxer, Richard; Bennett, Carol; Shelton, Jeremy] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA 90095 USA. [Boxer, Richard; Madison, Pauline; Kleinman, Leonard; Altman, Lisa; Bennett, Carol; Shelton, Jeremy] Vet Affairs Greater Los Angeles, Los Angeles, CA USA. [Skolarus, Ted] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. [Skolarus, Ted] Vet Affairs Ann Arbor, HSR&D Ctr Hlth Commun Res, Ann Arbor, MI USA. RP Chu, S (reprint author), Univ Calif Los Angeles, Dept Urol, Los Angeles, CA 90095 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD AUG PY 2015 VL 86 IS 2 BP 260 EP 261 DI 10.1016/j.urology.2015.04.040 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA CS2MJ UT WOS:000361904800018 PM 26169002 ER PT J AU Benedict, C Dahn, JR Antoni, MH Traeger, L Kava, B Bustillo, N Zhou, ES Penedo, FJ AF Benedict, Catherine Dahn, Jason R. Antoni, Michael H. Traeger, Lara Kava, Bruce Bustillo, Natalie Zhou, Eric S. Penedo, Frank J. TI Positive and negative mood in men with advanced prostate cancer undergoing androgen deprivation therapy: considering the role of social support and stress SO PSYCHO-ONCOLOGY LA English DT Article DE cancer; oncology; mental health; affective aspects; social support; psychological stress ID QUALITY-OF-LIFE; BREAST-CANCER; PERCEIVED STRESS; MAJOR DEPRESSION; HEALTH LITERACY; ASSOCIATION; DIAGNOSIS; SURVIVORS; DISTRESS; ILLNESS AB Advanced prostate cancer patients often undergo androgen deprivation therapy (ADT). Advanced disease and adverse ADT side effects are often debilitating and negatively impact mood. Social support has been shown to mitigate detrimental effects of stress on mood. ObjectiveThis study sought to characterize positive and negative mood in this select patient population and determine whether social support moderated relations between stress and mood. MethodsParticipants (N=80) completed the Interpersonal Support Evaluation List, Perceived Stress Scale, and Derogatis Affect Balance Scale at a single time point. Hierarchical regression models evaluated relations among social support, stress, and mood controlling for relevant covariates. Standard moderation analyses were performed. ResultsParticipants reported higher levels of negative and positive mood compared with published means of localized prostate cancer patients. Overall, mood was more positive than negative. Stress levels were comparable to cancer populations with recurrent disease. Moderated regression analyses showed that social support partially buffered the effects of stress on positive mood; men with high stress and low support reported the lowest levels of positive mood. The model with negative mood as the dependent measure did not support moderation; that is, the relationship between stress and negative mood did not differ by level of social support. ConclusionAmong individuals living with advanced prostate cancer, social support may be an important factor that sustains positive mood in the presence of stress. Future work should examine the extent to which social support prospectively impacts health-related quality of life by promoting positive mood. Limitations include cross-sectional design, which precludes causal inferences. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Benedict, Catherine] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10022 USA. [Dahn, Jason R.] Miami Vet Affairs Healthcare Syst, Miami, FL USA. [Antoni, Michael H.; Bustillo, Natalie] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. [Antoni, Michael H.] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA. [Traeger, Lara] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Kava, Bruce] Univ Miami, Miller Sch Med, Dept Urol, Miami, FL 33136 USA. [Zhou, Eric S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Penedo, Frank J.] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. RP Benedict, C (reprint author), Mem Sloan Kettering Canc Ctr, 641 Lexington St,7th Floor, New York, NY 10022 USA. EM benedicc@mskcc.org FU NCI NIH HHS [1R21CA102761-01A2] NR 50 TC 2 Z9 3 U1 5 U2 13 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 2015 VL 24 IS 8 BP 932 EP 939 DI 10.1002/pon.3681 PG 8 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CN7MO UT WOS:000358618900010 PM 25251737 ER PT J AU Buescher, JM Antoniewicz, MR Boros, LG Burgess, SC Brunengraber, H Clish, CB DeBerardinis, RJ Feron, O Frezza, C Ghesquiere, B Gottlieb, E Hiller, K Jones, RG Kamphorst, JJ Kibbey, RG Kimmelman, AC Locasale, JW Lunt, SY Maddocks, ODK Malloy, C Metallo, CM Meuillet, EJ Munger, J Noh, K Rabinowitz, JD Ralser, M Sauer, U Stephanopoulos, G St-Pierre, J Tennant, DA Wittmann, C Vander Heiden, MG Vazquez, A Vousden, K Young, JD Zamboni, N Fendt, SM AF Buescher, Joerg M. Antoniewicz, Maciek R. Boros, Laszlo G. Burgess, Shawn C. Brunengraber, Henri Clish, Clary B. DeBerardinis, Ralph J. Feron, Olivier Frezza, Christian Ghesquiere, Bart Gottlieb, Eyal Hiller, Karsten Jones, Russell G. Kamphorst, Jurre J. Kibbey, Richard G. Kimmelman, Alec C. Locasale, Jason W. Lunt, Sophia Y. Maddocks, Oliver D. K. Malloy, Craig Metallo, Christian M. Meuillet, Emmanuelle J. Munger, Joshua Noeh, Katharina Rabinowitz, Joshua D. Ralser, Markus Sauer, Uwe Stephanopoulos, Gregory St-Pierre, Julie Tennant, Daniel A. Wittmann, Christoph Vander Heiden, Matthew G. Vazquez, Alexei Vousden, Karen Young, Jamey D. Zamboni, Nicola Fendt, Sarah-Maria TI A roadmap for interpreting C-13 metabolite labeling patterns from cells SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Review ID REDUCTIVE GLUTAMINE-METABOLISM; MASS ISOTOPOMER DISTRIBUTIONS; PENTOSE-PHOSPHATE PATHWAY; FATTY-ACID SYNTHESIS; FLUX RATIO ANALYSIS; MAMMALIAN-CELLS; CORYNEBACTERIUM-GLUTAMICUM; NUCLEOTIDE SYNTHESIS; ALPHA-KETOGLUTARATE; CELLULAR-METABOLISM AB Measuring intracellular metabolism has increasingly led to important insights in biomedical research. C-13 tracer analysis, although less information-rich than quantitative C-13 flux analysis that requires computational data integration, has been established as a time-efficient method to unravel relative pathway activities, qualitative changes in pathway contributions, and nutrient contributions. Here, we review selected key issues in interpreting C-13 metabolite labeling patterns, with the goal of drawing accurate conclusions from steady state and dynamic stable isotopic tracer experiments. C1 [Buescher, Joerg M.; Ghesquiere, Bart; Fendt, Sarah-Maria] VIB, Vesalius Res Ctr, Leuven, Belgium. [Buescher, Joerg M.; Ghesquiere, Bart; Fendt, Sarah-Maria] Katholieke Univ Leuven, Dept Oncol, Leuven, Belgium. [Antoniewicz, Maciek R.] Univ Delaware, Dept Chem & Biomol Engn, Newark, DE USA. [Boros, Laszlo G.] Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles Biomed Res Inst,Harbor UCLA Med Ctr, Los Angeles, CA 90024 USA. [Boros, Laszlo G.] Sidmap LLC, Los Angeles, CA USA. [Burgess, Shawn C.; Malloy, Craig] Univ Texas SW Med Ctr Dallas, Adv Imaging Res Ctr, Div Metab Mech Dis, Dallas, TX 75390 USA. [Burgess, Shawn C.] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA. [Brunengraber, Henri] Case Western Reserve Univ, Sch Med, Dept Nutr, Cleveland, OH USA. [Clish, Clary B.] Broad Inst Harvard & MIT, Cambridge, MA USA. [DeBerardinis, Ralph J.] Univ Texas SW Med Ctr Dallas, Childrens Med Ctr, Res Inst, Dallas, TX 75390 USA. [Feron, Olivier] Catholic Univ Louvain, Pole Pharmacol & Therapeut FATH, IREC, B-1200 Brussels, Belgium. [Frezza, Christian] Univ Cambridge, Hutchison MRC Res Ctr, MRC Canc Unit, Cambridge, England. [Gottlieb, Eyal; Maddocks, Oliver D. K.; Vazquez, Alexei; Vousden, Karen] Canc Res UK, Beatson Inst, Glasgow, Lanark, Scotland. [Hiller, Karsten] Univ Luxembourg, Luxembourg Ctr Syst Biomed, Esch Belval, Luxembourg. [Jones, Russell G.] McGill Univ, Dept Physiol, Goodman Canc Res Ctr, Montreal, PQ, Canada. [Kamphorst, Jurre J.] Univ Glasgow, Inst Canc Sci, Glasgow, Lanark, Scotland. [Kibbey, Richard G.] Yale Univ, Sch Med, Internal Med Cellular & Mol Physiol, New Haven, CT USA. [Kimmelman, Alec C.] Dana Farber Canc Inst, Dept Radiat Oncol, Div Genom Stabil & DNA Repair, Boston, MA 02115 USA. [Locasale, Jason W.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. [Lunt, Sophia Y.] Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. [Malloy, Craig] Univ Texas SW Med Ctr Dallas, Dept Radiol, Dallas, TX 75390 USA. [Metallo, Christian M.] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. [Meuillet, Emmanuelle J.] Inst Technol Avancees Sci Vivant ITAV, Toulouse 1, France. [Meuillet, Emmanuelle J.] Univ Arizona, Ctr Canc, Tucson, AZ USA. [Meuillet, Emmanuelle J.] Univ Arizona, Dept Nutr Sci, Tucson, AZ USA. [Munger, Joshua] Univ Rochester, Med Ctr, Dept Biochem, Rochester, NY 14642 USA. [Munger, Joshua] Univ Rochester, Med Ctr, Dept Biophys, Rochester, NY 14642 USA. [Noeh, Katharina] Forschungszentrum Julich, Inst Bio & Geosci, IBG Biotechnol 1, D-52425 Julich, Germany. [Rabinowitz, Joshua D.] Princeton Univ, Dept Chem, Princeton, NJ 08544 USA. [Rabinowitz, Joshua D.] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA. [Ralser, Markus] Univ Cambridge, Cambridge Syst Biol Ctr, Cambridge, England. [Ralser, Markus] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England. [Ralser, Markus] MRC Natl Inst Med Res, Div Physiol & Metab, London, England. [Sauer, Uwe; Zamboni, Nicola] ETH, Inst Mol Syst Biol, Zurich, Switzerland. [Stephanopoulos, Gregory] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [St-Pierre, Julie] McGill Univ, Goodman Canc Res Ctr, Montreal, PQ, Canada. [St-Pierre, Julie] McGill Univ, Dept Biochem, Montreal, PQ, Canada. [Tennant, Daniel A.] Univ Birmingham, Sch Canc Sci, Coll Med & Dent Sci, Birmingham, W Midlands, England. [Wittmann, Christoph] Univ Saarland, Inst Syst Biotechnol, D-66123 Saarbrucken, Germany. [Vander Heiden, Matthew G.] MIT, Broad Inst Harvard & MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Vander Heiden, Matthew G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Young, Jamey D.] Vanderbilt Univ, Dept Chem & Biomol Engn, Nashville, TN 37235 USA. [Young, Jamey D.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. RP Fendt, SM (reprint author), VIB, Vesalius Res Ctr, Leuven, Belgium. EM sarah-maria.fendt@vib-kuleuven.be RI Young, Jamey/A-5857-2012; Gottlieb, Eyal/G-6450-2010; Maddocks, Oliver/K-5410-2012; OI Gottlieb, Eyal/0000-0002-9770-0956; Maddocks, Oliver/0000-0002-5551-9091; Buescher, Joerg Martin/0000-0002-6547-0076; Kamphorst, Jurre/0000-0002-2042-5474; Lunt, Sophia/0000-0003-4522-6065; Ralser, Markus/0000-0001-9535-7413; Tennant, Daniel/0000-0003-0499-2732; Locasale, Jason/0000-0002-7766-3502 FU Marie Curie - CIG; FWO - Odysseus; Concern Foundation; FWO - Research Grants; EugeIne Yourassowsky Schenking; Bayer Health Care FX We thank Dimitrios Anastasiou, Chi V. Dang, Teresa W.-M. Fan, Richard M. Higashi, Andrew N. Lane, and Hunter Moseley for the support and discussions, and Stefan Christen, Ben Pirongs, Gianmarco Rinaldi, Roberta Schmieder, and Yiping Wang for their feedback on the manuscript. SMF acknowledges funding support from Marie Curie - CIG, FWO - Odysseus, Concern Foundation, FWO - Research Grants, EugeIne Yourassowsky Schenking, and Bayer Health Care. NR 101 TC 66 Z9 66 U1 18 U2 62 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0958-1669 EI 1879-0429 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD AUG PY 2015 VL 34 BP 189 EP 201 DI 10.1016/j.copbio.2015.02.003 PG 13 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA CR3TP UT WOS:000361256300026 PM 25731751 ER PT J AU Ramsuran, V Kulkarni, S O'huigin, C Yuki, Y Augusto, DG Gao, XJ Carrington, M AF Ramsuran, Veron Kulkarni, Smita O'huigin, Colm Yuki, Yuko Augusto, Danillo G. Gao, Xiaojiang Carrington, Mary TI Epigenetic regulation of differential HLA-A allelic expression levels SO HUMAN MOLECULAR GENETICS LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I MOLECULE; DNA METHYLATION; HIV CONTROL; GENE-EXPRESSION; C EXPRESSION; MHC; CELLS; BINDING; GENOME AB MHC class I expression levels influence the strength of immune responses and represent another variable in determining outcome to disease beyond peptide binding alone. Identification of the HLA loci that vary in allelic expression levels and delineating the mechanism responsible for expression variation may provide the opportunity to modify their expression therapeutically. We have examined the expression levels of allelic lineages at the HLA-A locus in a sample of 216 European Americans using a real-time polymerase chain reaction assay, which amplifies all HLA-A lineages specifically with equal efficiency, and observed a gradient of expression that associates with HLA-A allelic lineage (R = 0.6, P = 5 x 10(-25)). DNA methylation of the HLA-A gene appears to contribute to the variation in HLA-A mRNA expression levels, as a significant inverse correlation was observed between HLA-A mRNA expression levels in untreated cells and the degree to which expression is increased after treatment of the cells with a DNA methyltransferase inhibitor (R = 0.6, P = 2.8 x 10(-6)). Further, deep-sequencing and immunoprecipitation assays revealed allelic lineage-specific methylation patterns within the HLA-A promoter region where increased DNA methylation levels correlated significantly with reduced HLA-A expression levels (R = 0.89, P = 3.7 x 10(-9)). These data demonstrate HLA-A allelic lineage-specific variation in expression levels, and DNA methylation as a likely factor in contributing to this variation. C1 [Ramsuran, Veron; O'huigin, Colm; Yuki, Yuko; Augusto, Danillo G.; Gao, Xiaojiang; Carrington, Mary] Leidos Biomedical Res Inc, Frederick Natl Lab Canc Res, Expt Immunol Lab, Canc Inflammat Program, Frederick, MD 21702 USA. [Ramsuran, Veron; Kulkarni, Smita; Augusto, Danillo G.; Carrington, Mary] MIT, Massachusetts Gen Hosp, Ragon Inst, Cambridge, MA 02139 USA. [Ramsuran, Veron; Kulkarni, Smita; Augusto, Danillo G.; Carrington, Mary] Harvard Univ, Cambridge, MA 02139 USA. RP Carrington, M (reprint author), Leidos Biomedical Res Inc, Frederick Natl Lab Canc Res, Expt Immunol Lab, Canc Inflammat Program, Frederick, MD 21702 USA. EM carringm@mail.nih.gov RI Augusto, Danillo/F-3147-2013 FU National Cancer Institute, National Institutes of Health (NIH) [HHSN261200800001E, N02-CP-55504, R01-DA04334, R01-DA12568]; NIH, Frederick National Lab, Center for Cancer Research FX This work was supported by federal funds from the National Cancer Institute, National Institutes of Health (NIH), [grant numbers HHSN261200800001E, N02-CP-55504, R01-DA04334 and R01-DA12568]. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. This Research was supported in part by the Intramural Research Program of the NIH, Frederick National Lab, Center for Cancer Research. NR 38 TC 6 Z9 6 U1 1 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 2015 VL 24 IS 15 BP 4268 EP 4275 DI 10.1093/hmg/ddv158 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CR4OK UT WOS:000361314100007 PM 25935001 ER PT J AU Oh, SY He, F Krans, A Frazer, M Taylor, JP Paulson, HL Todd, PK AF Oh, Seok Yoon He, Fang Krans, Amy Frazer, Michelle Taylor, J. Paul Paulson, Henry L. Todd, Peter K. TI RAN translation at CGG repeats induces ubiquitin proteasome system impairment in models of fragile X-associated tremor ataxia syndrome SO HUMAN MOLECULAR GENETICS LA English DT Article ID RNA-MEDIATED NEURODEGENERATION; C9ORF72 HEXANUCLEOTIDE REPEAT; AGGREGATE-PRONE PROTEINS; ALPHA-SYNUCLEIN TOXICITY; FMR1 MESSENGER-RNA; TREMOR/ATAXIA SYNDROME; DROSOPHILA MODEL; MYOTONIC-DYSTROPHY; ANTISENSE TRANSCRIPTS; PREMUTATION ALLELES AB Fragile X-associated tremor ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a CGG trinucleotide repeat expansion in the 5'UTR of the Fragile X gene, FMR1. FXTAS is thought to arise primarily from an RNA gain-of-function toxicity mechanism. However, recent studies demonstrate that the repeat also elicits production of a toxic polyglycine protein, FMRpolyG, via repeat-associated non-AUG (RAN)-initiated translation. Pathologically, FXTAS is characterized by ubiquitin-positive intranuclear neuronal inclusions, raising the possibility that failure of protein quality control pathways could contribute to disease pathogenesis. To test this hypothesis, we used Drosophila-and cell-based models of CGG-repeat-associated toxicity. In Drosophila, ubiquitin proteasome system (UPS) impairment led to enhancement of CGG-repeat-induced degeneration, whereas overexpression of the chaperone protein HSP70 suppressed this toxicity. In transfected mammalian cells, CGG repeat expression triggered accumulation of a UPS reporter in a length-dependent fashion. To delineate the contributions from CGG repeats as RNA from RAN translation-associated toxicity, we enhanced or impaired the production of FMRpolyG in these models. Driving expression of FMRpolyG enhanced induction of UPS impairment in cell models, while prevention of RAN translation attenuated UPS impairment in cells and suppressed the genetic interaction with UPS manipulation in Drosophila. Taken together, these findings suggest that CGG repeats induce UPS impairment at least in part through activation of RAN translation. C1 [Oh, Seok Yoon; He, Fang; Krans, Amy; Frazer, Michelle; Paulson, Henry L.; Todd, Peter K.] Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA. [Taylor, J. Paul] St Jude Childrens Res Hosp, Dept Cell & Mol Biol, Memphis, TN 38105 USA. [Todd, Peter K.] US Dept Vet Affairs, Med Ctr, Neurol, Ann Arbor, MI USA. RP Todd, PK (reprint author), 4005 BSRB,109 Zina Pitcher Pl, Ann Arbor, MI 48109 USA. EM petertod@umich.edu FU National Ataxia Foundation; AAN CRTF fellowship; NIH [R01NS08681001, K08NS069809]; Department of Veterans Affairs BLRD [1I21BX001841] FX Funding for this project was derived from a National Ataxia Foundation grant to F.H. and an AAN CRTF fellowship, NIH R01NS08681001, NIH K08NS069809 and the Department of Veterans Affairs BLRD 1I21BX001841 to P.K.T. NR 75 TC 13 Z9 13 U1 3 U2 5 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 2015 VL 24 IS 15 BP 4317 EP 4326 DI 10.1093/hmg/ddv165 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CR4OK UT WOS:000361314100012 PM 25954027 ER PT J AU Blakney, R Gudnadottir, U Warrack, S O'Horo, JC Anderson, M Sethi, A Schmitz, M Wang, J Duster, M Ide, E Safdar, N AF Blakney, Rebekah Gudnadottir, Unnur Warrack, Simone O'Horo, John C. Anderson, Michael Sethi, Ajay Schmitz, Michelle Wang, Jennifer Duster, Megan Ide, Emma Safdar, Nasia TI The relationship between patient functional status and environmental contamination by Clostridium difficile: a pilot study SO INFECTION LA English DT Article DE Healthcare-associated infections; Clostridium difficile; Environmental contamination; Infection control ID STRAIN AB Introduction Limited data exist on patient factors related to environmental contamination with Clostridium difficile. Methods We evaluated the association between the functional status of patients with C. difficile infection (CDI) and environmental contamination with C. difficile. Results Contamination of patient rooms was frequent and higher functional status was associated with contaminated surfaces remote from the bed. All but one environmental isolates matched the corresponding patient's stool isolate for the seven patients tested. Conclusion Functional status is a factor that influences environmental contamination with C. difficile. Future studies should evaluate strategies to reduce contamination in CDI patient rooms, taking into account the patient's functional status. C1 [Blakney, Rebekah; Gudnadottir, Unnur; Sethi, Ajay; Safdar, Nasia] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI 53705 USA. [Blakney, Rebekah; Warrack, Simone; Anderson, Michael; Wang, Jennifer; Duster, Megan; Safdar, Nasia] Univ Wisconsin, Dept Med, Madison, WI 53705 USA. [O'Horo, John C.] Mayo Clin, Dept Med, Rochester, MN USA. [Schmitz, Michelle] Univ Wisconsin, Dept Nat Sci, Madison, WI 53705 USA. [Ide, Emma; Safdar, Nasia] Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. [Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Safdar, N (reprint author), Univ Wisconsin, Dept Populat Hlth Sci, 5221 MFCB,1685 Highland Ave, Madison, WI 53705 USA. EM ns2@medicine.wisc.edu RI O'Horo, John/N-8681-2013 OI O'Horo, John/0000-0002-0880-4498 FU NIA NIH HHS [AG40669, R03 AG040669] NR 10 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0300-8126 EI 1439-0973 J9 INFECTION JI Infection PD AUG PY 2015 VL 43 IS 4 BP 483 EP 487 DI 10.1007/s15010-015-0770-1 PG 5 WC Infectious Diseases SC Infectious Diseases GA CR4JU UT WOS:000361299000010 PM 25869819 ER PT J AU Fernandes, L Mateos, R Engedal, K von Gunten, A Stek, ML Ramakrishnan, A Ihl, R Wang, HL Mintzer, J Brodaty, H AF Fernandes, Lia Mateos, Raimundo Engedal, Knut von Gunten, Armin Stek, Max L. Ramakrishnan, Anand Ihl, Ralf Wang, Huali Mintzer, Jacobo Brodaty, Henry CA Int Psychogeriatric Association TI The state of psychogeriatrics in Europe: challenges and opportunities in six European countries SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Editorial Material ID PSYCHIATRY C1 [Fernandes, Lia] Univ Porto, Fac Med, UNIFAI CINTESIS, P-4100 Oporto, Portugal. [Mateos, Raimundo] Fac Med Santiago de Compostela, Dept Psiquiatria, Santiago De Compostela, Spain. [Engedal, Knut] Vestfold Hosp Trust, Norwegian Ctr Aging & Hlth, Tonsberg, Norway. [von Gunten, Armin] Univ Lausanne Hosp, Dept Psychiat, Serv Univ Psychiat Age Aavance, Prilly, Switzerland. [Stek, Max L.] Acad Werkplaats Ouderenpsychiat GGZ inGeest VUmc, Dept Old Age Psychiat, Amsterdam, Netherlands. [Ramakrishnan, Anand] Royal Coll Psychiatrists, Fac Old Age Psychiat, London SW1X 8PG, England. [Ihl, Ralf] Univ Dusseldorf, Dept Psychiat & Psychotherapy, Krefeld, Germany. [Ihl, Ralf] Alexian Res Ctr, Krefeld, Germany. [Wang, Huali] Peking Univ, Minist Hlth, Inst Mental Hlth, Key Lab Mental Hlth, Beijing 100871, Peoples R China. [Mintzer, Jacobo] Roper St Francis Healthcare, Clin Biotechnol Res Inst, Charleston, SC USA. [Mintzer, Jacobo] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Brodaty, Henry] Univ New S Wales, Ctr Hlth Brain Ageing, Sydney, NSW, Australia. RP Fernandes, L (reprint author), Univ Porto, Fac Med, UNIFAI CINTESIS, Rua Campo Alegre 823, P-4100 Oporto, Portugal. EM lfernandes@med.up.pt RI FMUP, CINTESIS/C-6631-2014; OI FMUP, CINTESIS/0000-0001-7248-2086; Fernandes, Lia/0000-0002-3391-0647 NR 16 TC 1 Z9 1 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1041-6102 EI 1741-203X J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PD AUG PY 2015 VL 27 IS 8 BP 1243 EP 1246 DI 10.1017/S1041610214002191 PG 4 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA CR5LR UT WOS:000361384500001 PM 25355137 ER PT J AU Teuffel, P Wang, L Prinz, P Goebel-Stengel, M Scharner, S Kobelt, P Hofmann, T Rose, M Klapp, BF Reeve, JR Stengel, A AF Teuffel, P. Wang, L. Prinz, P. Goebel-Stengel, M. Scharner, S. Kobelt, P. Hofmann, T. Rose, M. Klapp, B. F. Reeve, J. R., Jr. Stengel, A. TI TREATMENT WITH THE GHRELIN-O-ACYLTRANSFERASE (GOAT) INHIBITOR GO-COA-TAT REDUCES FOOD INTAKE BY REDUCING MEAL FREQUENCY IN RATS SO JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY LA English DT Article DE automated food intake monitoring system; behavior; behavioral satiety sequence; food intake pattern; ghrelin ID BEHAVIORAL SATIETY SEQUENCE; BODY-MASS INDEX; PATTERN-ANALYSIS; MICROSTRUCTURE; PEPTIDE; MICE; INCREASES; RECEPTOR; HORMONE; OBESITY AB The ghrelin acylating enzyme ghrelin-O-acyltransferase (GOAT) was recently identified and implicated in several biological functions. However, the effects on food intake warrant further investigation. While several genetic GOAT mouse models showed normal food intake, acute blockade using a GOAT inhibitor resulted in reduced food intake. The underlying food intake microstructure remains to be established. In the present study we used an automated feeding monitoring system to assess food intake and the food intake microstructure. First, we validated the basal food intake and feeding behavior in rats using the automated monitoring system. Afterwards, we assessed the food intake microstructure following intraperitoneal injection of the GOAT inhibitor, GO-CoA-Tat (32, 96 and 288 mu g/kg) in freely fed male Sprague-Dawley rats. Rats showed a rapid habituation to the automated food intake monitoring system and food intake levels were similar compared to manual monitoring (P = 0.43). Rats housed under these conditions showed a physiological behavioral satiety sequence. Injection of the GOAT inhibitor resulted in a dose-dependent reduction of food intake with a maximum effect observed after 96 mu g/kg (-27%, P = 0.03) compared to vehicle. This effect was delayed in onset as the first meal was not altered and lasted for a period of 2 h. Analysis of the food intake microstructure showed that the anorexigenic effect was due to a reduction of meal frequency (-15%, P = 0.04), whereas meal size (P = 0.29) was not altered compared to vehicle. In summary, pharmacological blockade of GOAT reduces dark phase food intake by an increase of satiety while satiation is not affected. C1 [Teuffel, P.; Prinz, P.; Scharner, S.; Kobelt, P.; Hofmann, T.; Rose, M.; Klapp, B. F.; Stengel, A.] Charite, Charite Ctr Internal Med & Dermatol, Div Gen Internal & Psychosomat Med, D-12200 Berlin, Germany. [Wang, L.; Reeve, J. R., Jr.] Univ Calif Los Angeles, Div Digest Dis, Dept Med, CURE Digest Dis Res Ctr,Ctr Neurobiol Stress, Los Angeles, CA 90024 USA. [Wang, L.; Reeve, J. R., Jr.] Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. [Goebel-Stengel, M.] Martin Luther Krankenhaus, Dept Internal Med, Berlin, Germany. [Goebel-Stengel, M.] Martin Luther Krankenhaus, Inst Neurogastroenterol, Berlin, Germany. RP Stengel, A (reprint author), Charite, Ctr Internal Med & Dermatol, Div Gen Internal & Psychosomat Med, 30 Hindenburgdamm St, D-12200 Berlin, Germany. EM andreas.stengel@charite.de FU German Research Foundation Grants [STE 1765/3-1, R01 NIH DK083449]; Sonnenfeld Foundation Berlin; Charite University Funding [UFF 89/441-176] FX This work was supported by German Research Foundation Grants STE 1765/3-1 (A.S.), R01 NIH DK083449 (J.R.R., Jr.), the Sonnenfeld Foundation Berlin (A.S.) and Charite University Funding UFF 89/441-176 (A.S.). NR 50 TC 3 Z9 3 U1 1 U2 2 PU POLISH PHYSIOLOGICAL SOC PI GRZEGORZECKA PA JAGIELLONIAN UNIV SCHOOL MED, INST PHYSIOLOGY, 31-531 KRAKOW, 16 GRZEGORZECKA, POLAND SN 0867-5910 J9 J PHYSIOL PHARMACOL JI J. Physiol. Pharmacol. PD AUG PY 2015 VL 66 IS 4 BP 493 EP 503 PG 11 WC Physiology SC Physiology GA CR7AL UT WOS:000361499800003 PM 26348074 ER PT J AU Rosendorff, C AF Rosendorff, Clive TI Treatment: special conditions Co-existing heart disease: coronary artery disease, myocardial infarction, heart failure SO JOURNAL OF THE AMERICAN SOCIETY OF HYPERTENSION LA English DT Article ID ASSOCIATION TASK-FORCE; PRACTICE GUIDELINES; FOCUSED UPDATE; BLOOD-PRESSURE; PREVENTION; MANAGEMENT; HYPERTENSION AB There is a strong epidemiologic association between hypertension (HT) and coronary artery disease (CAD). In men older than the age of 65 years, HT increases the relative risk of CAD to 1.6, of stroke to 2.0, and heart failure (HF) to 1.9. The figures for women of the same age are even worse: 1.9, 2.6, and 1.9. Consequently, HT and CAD commonly occur together and raise some unique problems of management. These include the elusive definition of the blood pressure (BP) goal of therapy in these patients and the optimal choice of the treatment of HT, both for the prevention and management of CAD. C1 Icahn Sch Med Mt Sinai, Dept Med, James J Peters VA Med Ctr, Bronx, NY 10029 USA. RP Rosendorff, C (reprint author), Icahn Sch Med Mt Sinai, Dept Med, James J Peters VA Med Ctr, 130 West Kingsbridge Rd, Bronx, NY 10029 USA. EM clive.rosendorff@va.gov NR 10 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 1933-1711 EI 1878-7436 J9 J AM SOC HYPERTENS JI J. Am. Soc. Hypertens. PD AUG PY 2015 VL 9 IS 8 BP 651 EP 654 DI 10.1016/j.jash.2015.06.008 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CR4XI UT WOS:000361343000014 PM 26183895 ER PT J AU Kamei, CN Liu, Y Drummond, IA AF Kamei, Caramai N. Liu, Yan Drummond, Iain A. TI Kidney Regeneration in Adult Zebrafish by Gentamicin Induced Injury SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Developmental Biology; Issue 102; kidney; mesonephros; gentamicin; injection; zebrafish; injury; regeneration; Lhx1a; heat shock; adult ID TRANSGENIC ZEBRAFISH; REPAIR; PROGENITORS; ABLATION; CELLS AB The kidney is essential for fluid homeostasis, blood pressure regulation and filtration of waste from the body. The fundamental unit of kidney function is the nephron. Mammals are able to repair existing nephrons after injury, but lose the ability to form new nephrons soon after birth. In contrast to mammals, adult fish produce new nephrons (neonephrogenesis) throughout their lives in response to growth requirements or injury. Recently, lhx1a has been shown to mark nephron progenitor cells in the adult zebrafish kidney, however mechanisms controlling the formation of new nephrons after injury remain unknown. Here we show our method for robust and reproducible injury in the adult zebrafish kidney by intraperitoneal (i.p.) injection of gentamicin, which uses a noninvasive visual screening process to select for fish with strong but nonlethal injury. Using this method, we can determine optimal gentamicin dosages for injury and go on to demonstrate the effect of higher temperatures on kidney regeneration in zebrafish. C1 [Kamei, Caramai N.; Liu, Yan; Drummond, Iain A.] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Liu, Yan] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA USA. [Drummond, Iain A.] Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02138 USA. RP Drummond, IA (reprint author), Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. EM idrummond@mgh.harvard.edu FU NIH grant [F32DK091998, RO1DK041071]; Harvard Stem Cell Institute grant [D001229] FX This work was supported by NIH grant F32DK091998 to CNK; NIH grant RO1DK041071 and Harvard Stem Cell Institute grant D001229 to IAD. The authors thank Neil Hukriede for the lhx1ain situ probe. NR 19 TC 0 Z9 0 U1 2 U2 8 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD AUG PY 2015 IS 102 AR e51912 DI 10.3791/51912 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CR7NL UT WOS:000361537100004 PM 26275011 ER PT J AU Vlahovic, G Fecci, PE Reardon, D Sampson, JH AF Vlahovic, Gordana Fecci, Peter E. Reardon, David Sampson, John H. TI Programmed death ligand 1 (PD-L1) as an immunotherapy target in patients with glioblastoma SO NEURO-ONCOLOGY LA English DT Editorial Material ID B7-H1 EXPRESSION; CANCER; ANTIBODY; GLIOMAS; SAFETY C1 [Vlahovic, Gordana; Fecci, Peter E.; Sampson, John H.] Duke Univ, Sch Med, Preston Robert Tisch Brain Tumor Ctr, Div Neurosurg, Durham, NC 27710 USA. [Reardon, David] Dana Farber Canc Inst, Boston, MA 02115 USA. [Reardon, David] Harvard Univ, Sch Med, Boston, MA USA. RP Sampson, JH (reprint author), Duke Univ, Med Ctr, Div Neurosurg, Box 3050,220 Sands Bldg,Res Dr, Durham, NC 27710 USA. EM john.sampson@duke.edu NR 17 TC 6 Z9 6 U1 1 U2 8 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 2015 VL 17 IS 8 BP 1043 EP 1045 DI 10.1093/neuonc/nov071 PG 3 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CR4MC UT WOS:000361305700001 PM 25964311 ER PT J AU Prados, MD Byron, SA Tran, NL Phillips, JJ Molinaro, AM Ligon, KL Wen, PY Kuhn, JG Mellinghoff, IK de Groot, JF Colman, H Cloughesy, TF Chang, SM Ryken, TC Tembe, WD Kiefer, JA Berens, ME Craig, DW Carpten, JD Trent, JM AF Prados, Michael D. Byron, Sara A. Tran, Nhan L. Phillips, Joanna J. Molinaro, Annette M. Ligon, Keith L. Wen, Patrick Y. Kuhn, John G. Mellinghoff, Ingo K. de Groot, John F. Colman, Howard Cloughesy, Timothy F. Chang, Susan M. Ryken, Timothy C. Tembe, Waibhav D. Kiefer, Jeffrey A. Berens, Michael E. Craig, David W. Carpten, John D. Trent, Jeffrey M. TI Toward precision medicine in glioblastoma: the promise and the challenges SO NEURO-ONCOLOGY LA English DT Article DE clinical trial; genomics; glioblastoma; precision medicine; targeted therapy ID NEWLY-DIAGNOSED GLIOBLASTOMA; BRAIN-TUMOR CONSORTIUM; CONVECTION-ENHANCED DELIVERY; INTEGRATED GENOMIC ANALYSIS; RECURRENT MALIGNANT GLIOMA; FACTOR RECEPTOR INHIBITORS; TYROSINE KINASE INHIBITOR; PROGRESSION-FREE SURVIVAL; RANDOMIZED PHASE-III; ADJUVANT TEMOZOLOMIDE AB Integrated sequencing strategies have provided a broader understanding of the genomic landscape and molecular classifications of multiple cancer types and have identified various therapeutic opportunities across cancer subsets. Despite pivotal advances in the characterization of genomic alterations in glioblastoma, targeted agents have shown minimal efficacy in clinical trials to date, and patient survival remains poor. In this review, we highlight potential reasons why targeting single alterations has yielded limited clinical efficacy in glioblastoma, focusing on issues of tumor heterogeneity and pharmacokinetic failure. We outline strategies to address these challenges in applying precision medicine to glioblastoma and the rationale for applying targeted combination therapy approaches that match genomic alterations with compounds accessible to the central nervous system. C1 [Prados, Michael D.; Phillips, Joanna J.; Molinaro, Annette M.; Chang, Susan M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Byron, Sara A.; Tran, Nhan L.; Tembe, Waibhav D.; Kiefer, Jeffrey A.; Berens, Michael E.; Craig, David W.; Carpten, John D.; Trent, Jeffrey M.] Translat Genom Res Inst, Phoenix, AZ USA. [Ligon, Keith L.; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Kuhn, John G.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Mellinghoff, Ingo K.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [de Groot, John F.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Colman, Howard] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Cloughesy, Timothy F.] Univ Calif Los Angeles, Los Angeles, CA USA. [Ryken, Timothy C.] Iowa Spine & Brain Inst, Waterloo, IA USA. RP Prados, MD (reprint author), Univ Calif San Francisco, Dept Neurol Surg, 400 Parnassus,Room A-808, San Francisco, CA 94143 USA. EM pradosm@neurosurg.ucsf.edu FU Ben and Catherine Ivy Foundation FX This work was supported by the Ben and Catherine Ivy Foundation. NR 143 TC 20 Z9 21 U1 3 U2 11 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 2015 VL 17 IS 8 BP 1051 EP 1063 DI 10.1093/neuonc/nov031 PG 13 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CR4MC UT WOS:000361305700003 PM 25934816 ER PT J AU Trippa, L Wen, PY Parmigiani, G Berry, DA Alexander, BM AF Trippa, Lorenzo Wen, Patrick Y. Parmigiani, Giovanni Berry, Donald A. Alexander, Brian M. TI Combining progression-free survival and overall survival as a novel composite endpoint for glioblastoma trials SO NEURO-ONCOLOGY LA English DT Article DE adaptive clinical trials; auxiliary endpoints; clinical trial; endpoints; overall survival; progression-free survival ID NEWLY-DIAGNOSED GLIOBLASTOMA; RANDOMIZED-TRIAL; TEMOZOLOMIDE; BEVACIZUMAB; CONCOMITANT; GLIOMAS; DESIGN AB Background. The use of auxiliary endpoints may provide efficiencies for clinical trial design, but such endpoints may not have intrinsic clinical relevance or clear linkage to more meaningful endpoints. The purpose of this study was to generate a novel endpoint that considers both overall survival (OS) and earlier events such as progression-free survival (PFS) and determine whether such an endpoint could increase efficiency in the design of glioblastoma clinical trials. Methods. Recognizing that the association between PFS and OS varies depending on therapy and tumor type, we developed a statistical model to predict OS based on PFS as the trial progresses. We then evaluated the efficiency of our model using simulations of adaptively randomized trials incorporating PFS and OS distributions from prior published trials in neuro-oncology. Results. When treatment effects on PFS and OS are concordant, our proposed approach results in efficiency gains compared with randomization based on OS alone while sacrificing minimal efficiency compared with using PFS as the primary endpoint. When treatment effects are limited to PFS, our approach provides randomization probabilities that are close to those based on OS alone. Conclusion. Use of OS as the primary endpoint, combined with statistical modeling of the relationship between OS and PFS during the course of the trial, results in more robust and efficient trial designs than using either endpoint alone. C1 [Trippa, Lorenzo; Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Trippa, Lorenzo; Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Wen, Patrick Y.; Alexander, Brian M.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. [Alexander, Brian M.] Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Berry, Donald A.] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. RP Alexander, BM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM bmalexander@lroc.harvard.edu FU Innovations in Regulatory Science Award from The Burroughs Wellcome Fund FX This work was supported by an Innovations in Regulatory Science Award from The Burroughs Wellcome Fund. NR 20 TC 3 Z9 3 U1 0 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 2015 VL 17 IS 8 BP 1106 EP 1113 DI 10.1093/neuonc/nou345 PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CR4MC UT WOS:000361305700008 PM 25568226 ER PT J AU Schmainda, KM Zhang, Z Prah, M Snyder, BS Gilbert, MR Sorensen, AG Barboriak, DP Boxerman, JL AF Schmainda, Kathleen M. Zhang, Zheng Prah, Melissa Snyder, Bradley S. Gilbert, Mark R. Sorensen, A. Gregory Barboriak, Daniel P. Boxerman, Jerrold L. TI Dynamic susceptibility contrast MRI measures of relative cerebral blood volume as a prognostic marker for overall survival in recurrent glioblastoma: results from the ACRIN 6677/RTOG 0625 multicenter trial SO NEURO-ONCOLOGY LA English DT Article DE bevacizumab; MRI; overall survival; rCBV; recurrent glioblastoma ID BEVACIZUMAB PLUS IRINOTECAN; HIGH-GRADE GLIOMA; SINGLE-AGENT BEVACIZUMAB; MALIGNANT GLIOMA; ANTIANGIOGENIC THERAPY; TUMOR ANGIOGENESIS; LEAKAGE-CORRECTION; CLINICAL-TRIAL; GRADIENT-ECHO; BRAIN-TUMORS AB Background. The study goal was to determine whether changes in relative cerebral blood volume (rCBV) derived from dynamic susceptibility contrast (DSC) MRI are predictive of overall survival (OS) in patients with recurrent glioblastoma multiforme (GBM) when measured 2, 8, and 16 weeks after treatment initiation. Methods. Patients with recurrent GBM (37/123) enrolled in ACRIN 6677/RTOG 0625, a multicenter, randomized, phase II trial of bevacizumab with irinotecan or temozolomide, consented to DSC-MRI plus conventional MRI, 21 with DSC-MRI at baseline and at least 1 postbaseline scan. Contrast-enhancing regions of interest were determined semi-automatically using pre- and postcontrast T1-weighted images. Mean tumor rCBV normalized to white matter (nRCBV) and standardized rCBV (sRCBV) were determined for these regions of interest. The OS rates for patients with positive versus negative changes from baseline in nRCBV and sRCBV were compared using Wilcoxon rank-sum and Kaplan-Meier survival estimates with log-rank tests. Results. Patients surviving at least 1 year (OS-1) had significantly larger decreases in nRCBV at week 2 (P=.0451) and sRCBV at week 16 (P=.014). Receiver operating characteristic analysis found the percent changes of nRCBV and sRCBV at week 2 and sRCBV at week 16, but not rCBV data at week 8, to be good prognostic markers for OS-1. Patients with positive change from baseline rCBV had significantly shorter OS than those with negative change at both week 2 and week 16 (P=.0015 and P=.0067 for nRCBV and P=.0251 and P=.0004 for sRCBV, respectively). Conclusions. Early decreases in rCBV are predictive of improved survival in patients with recurrent GBM treated with bevacizumab. C1 [Schmainda, Kathleen M.; Prah, Melissa] Med Coll Wisconsin, Dept Radiol, Milwaukee, WI 53226 USA. [Zhang, Zheng; Snyder, Bradley S.] Brown Univ, Dept Biostat, Providence, RI 02912 USA. [Zhang, Zheng; Snyder, Bradley S.] Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA. [Gilbert, Mark R.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Sorensen, A. Gregory] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. [Barboriak, Daniel P.] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. [Boxerman, Jerrold L.] Rhode Isl Hosp, Dept Diagnost Imaging, Providence, RI USA. [Boxerman, Jerrold L.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. RP Schmainda, KM (reprint author), Med Coll Wisconsin, Dept Radiol, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM kathleen@mcw.edu RI Barboriak, Daniel/M-4414-2015; Gilbert, Mark/J-7494-2016 OI Barboriak, Daniel/0000-0002-2536-6266; Gilbert, Mark/0000-0003-2556-9722 FU National Cancer Institute [U01-CA080098, U01-CA079778] FX ACRIN received funding from the National Cancer Institute through grants U01-CA080098 and U01-CA079778. NR 54 TC 13 Z9 13 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD AUG PY 2015 VL 17 IS 8 BP 1148 EP 1156 DI 10.1093/neuonc/nou364 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CR4MC UT WOS:000361305700013 PM 25646027 ER PT J AU Nowak, J Seidel, C Pietsch, T Alkonyi, B Fuss, TL Friedrich, C von Hoff, K Rutkowski, S Warmuth-Metz, M AF Nowak, Johannes Seidel, Carolin Pietsch, Torsten Alkonyi, Balint Fuss, Taylor Laura Friedrich, Carsten von Hoff, Katja Rutkowski, Stefan Warmuth-Metz, Monika TI Systematic comparison of MRI findings in pediatric ependymoblastoma with ependymoma and CNS primitive neuroectodermal tumor not otherwise specified SO NEURO-ONCOLOGY LA English DT Article DE CNS-PNET NOS; ependymoblastoma; ependymoma; magnetic resonance imaging; MRI ID TRUE ROSETTES ETANTR; OF-THE-LITERATURE; ABUNDANT NEUROPIL; EMBRYONAL TUMOR; POSTERIOR-FOSSA; MULTILAYERED ROSETTES; COMPUTED-TOMOGRAPHY; MAGNETIC-RESONANCE; BRAIN-TUMORS; SUPRATENTORIAL AB Background. Ependymoblastoma (EBL), ependymoma (EP), and primitive neuroectodermal tumors of the central nervous system not otherwise specified (CNS-PNET NOS) are pediatric brain tumors that can be differentiated by histopathology in the clinical setting. Recently, we described specific MRI features of EBL. In this study, we compare standardized MRI characteristics of EBL with EP and CNS-PNET NOS in a series comprising 22 patients in each group. Methods. All 66 centrally reviewed cases were obtained from the database of the German multicenter HIT trials. We systematically analyzed the initial MRI scans at diagnosis according to standardized criteria, and paired comparison was performed for EBL and EP, as well as for EBL and CNS-PNET NOS. Results. We found differences between EBL and EP regarding age at diagnosis, MR signal intensity, tumor margin and surrounding edema, presence and size of cysts, and contrast enhancement pattern. Although MRI appearance of EBL shares many features with CNS-PNET NOS, we revealed significant differences in terms of age at diagnosis, tumor volume and localization, tumor margins, edema, and contrast enhancement. Conclusion. This is the first study that systematically compares multiple parameters of MRI in pediatric EBL with findings in EP and CNS-PNET NOS. Although a definite differentiation by means of MRI alone might not be feasible in the individual case, we identify significant differences between these tumor entities. C1 [Nowak, Johannes; Seidel, Carolin; Alkonyi, Balint; Warmuth-Metz, Monika] Univ Hosp, Reference Ctr Neuroradiol, D-97080 Wurzburg, Germany. [Nowak, Johannes] Univ Hosp, Dept Radiol, D-97080 Wurzburg, Germany. [Seidel, Carolin; Fuss, Taylor Laura] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Pathol Res, Charlestown, MA USA. [Pietsch, Torsten] Brain Tumor Reference Ctr, Dept Neuropathol, Bonn, Germany. [Friedrich, Carsten; von Hoff, Katja; Rutkowski, Stefan] Univ Med Ctr Hamburg Eppendorf, Dept Pediat Hematol & Oncol, Hamburg, Germany. [Friedrich, Carsten] Univ Hosp, Dept Womens & Childrens Hlth, Div Pediat Oncol Hematol & Hemostaseol, Leipzig, Germany. RP Nowak, J (reprint author), Univ Hosp, Reference Ctr Neuroradiol, Josef Schneider Str 11, D-97080 Wurzburg, Germany. EM nowak_j1@ukw.de FU Deutsche Kinderkrebsstiftung (German Childhood Cancer Foundation) FX This work was supported by the Deutsche Kinderkrebsstiftung (German Childhood Cancer Foundation). NR 39 TC 1 Z9 1 U1 2 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD AUG PY 2015 VL 17 IS 8 BP 1157 EP 1165 DI 10.1093/neuonc/nov063 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CR4MC UT WOS:000361305700014 PM 25916887 ER PT J AU Smith, BA Trujillo-Priego, IA Lane, CJ Finley, JM Horak, FB AF Smith, Beth A. Trujillo-Priego, Ivan A. Lane, Christianne J. Finley, James M. Horak, Fay B. TI Daily Quantity of Infant Leg Movement: Wearable Sensor Algorithm and Relationship to Walking Onset SO SENSORS LA English DT Article DE infant; movement; growth and development; wearable sensors ID FULL-TERM INFANTS; LOW-BIRTH-WEIGHT; PRETERM INFANTS; SPONTANEOUS KICKING; DOWN-SYNDROME; COORDINATION; ORGANIZATION; PATTERNS; AGE AB Background: Normative values are lacking for daily quantity of infant leg movements. This is critical for understanding the relationship between the quantity of leg movements and onset of independent walking, and will begin to inform early therapy intervention for infants at risk for developmental delay. Methods: We used wearable inertial movement sensors to record full-day leg movement activity from 12 infants with typical development, ages 1-12 months. Each infant was tested three times across 5 months, and followed until the onset of independent walking. We developed and validated an algorithm to identify infant-produced leg movements. Results: Infants moved their legs tens of thousands of times per day. There was a significant effect of leg movement quantity on walking onset. Infants who moved their legs more walked later than infants who moved their legs less, even when adjusting for age, developmental level or percentile length. We will need a much larger sample to adequately capture and describe the effect of movement experience on developmental rate. Our algorithm defines a leg movement in a specific way (each pause or change in direction is counted as a new movement), and further assessment of movement characteristics are necessary before we can fully understand and interpret our finding that infants who moved their legs more walked later than infants who moved their legs less. Conclusions: We have shown that typically-developing infants produce thousands of leg movements in a typical day, and that this can be accurately captured in the home environment using wearable sensors. In our small sample we can identify there is an effect of leg movement quantity on walking onset, however we cannot fully explain it. C1 [Smith, Beth A.; Trujillo-Priego, Ivan A.; Finley, James M.] Univ So Calif, Div Biokinesiol & Phys Therapy, Los Angeles, CA 90089 USA. [Lane, Christianne J.] Univ So Calif, Keck Sch Med, Div Biostat, Dept Preventat Med, Los Angeles, CA 90089 USA. [Horak, Fay B.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Horak, Fay B.] Portland VA Med Ctr, Portland, OR 97239 USA. RP Smith, BA (reprint author), Univ So Calif, Div Biokinesiol & Phys Therapy, Los Angeles, CA 90089 USA. EM beth.smith@usc.edu; itrujill@usc.edu; christianne.lane@med.usc.edu; jmfinley@usc.edu; horakf@ohsu.edu RI Finley, James/I-5699-2016; Smith, Beth A./D-2914-2014 OI Finley, James/0000-0003-2679-2221; Smith, Beth A./0000-0003-2531-5394 FU American Physical Therapy Association Section on Pediatrics Research Grant 2 Award; Foundation for Physical Therapy (NIFTI); Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health [K12HD073945, 2R42HD071760]; National Center for Advancing Translational Sciences of the National Institutes of Health [UL1TR000130]; [K12-HD055929] FX Thank you to the infants and their families. Funding sources: This work was funded in part by an American Physical Therapy Association Section on Pediatrics Research Grant 2 Award (BAS). Smith's salary was supported by the Foundation for Physical Therapy (NIFTI to BAS) and currently her salary and research are supported by K12-HD055929 (Ottenbacher). Finley's and Horak's efforts were supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under Award Numbers K12HD073945 (Finley) and 2R42HD071760 (Horak). Study data were collected and managed using REDCap electronic data capture tools hosted at Oregon Health & Science University (OHSU) (1 UL1 RR024140 01). Research reported in this publication was partially supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR000130 (formerly by the National Center for Research Resources, Award Number UL1RR031986). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 20 TC 2 Z9 2 U1 4 U2 11 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1424-8220 J9 SENSORS-BASEL JI Sensors PD AUG PY 2015 VL 15 IS 8 BP 19006 EP 19020 DI 10.3390/s150819006 PG 15 WC Chemistry, Analytical; Electrochemistry; Instruments & Instrumentation SC Chemistry; Electrochemistry; Instruments & Instrumentation GA CQ9BS UT WOS:000360906500061 PM 26247951 ER PT J AU Sabri, O Sabbagh, MN Seibyl, J Barthel, H Akatsu, H Ouchi, Y Senda, K Murayama, S Ishii, K Takao, M Beach, TG Rowe, CC Leverenz, JB Ghetti, B Ironside, JW Catafau, AM Stephens, AW Mueller, A Koglin, N Hoffmann, A Roth, K Reininger, C Schulz-Schaeffer, WJ AF Sabri, Osama Sabbagh, Marwan N. Seibyl, John Barthel, Henryk Akatsu, Hiroyasu Ouchi, Yasuomi Senda, Kohei Murayama, Shigeo Ishii, Kenji Takao, Masaki Beach, Thomas G. Rowe, Christopher C. Leverenz, James B. Ghetti, Bernardino Ironside, James W. Catafau, Ana M. Stephens, Andrew W. Mueller, Andre Koglin, Norman Hoffmann, Anja Roth, Katrin Reininger, Cornelia Schulz-Schaeffer, Walter J. CA Florbetaben Phase 3 Study Grp TI Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer's disease: Phase 3 study SO ALZHEIMERS & DEMENTIA LA English DT Article DE Amyloid; PET; Florbetaben; Histopathology ID NATIONAL INSTITUTE; F-18-FLORBETABEN; DIAGNOSIS AB Background: Evaluation of brain beta-amyloid by positron emission tomography (PET) imaging can assist in the diagnosis of Alzheimer disease (AD) and other dementias. Methods: Open-label, nonrandomized, multicenter, phase 3 study to validate the F-18-labeled beta-amyloid tracer florbetaben by comparing in vivo PET imaging with post-mortem histopathology. Results: Brain images and tissue from 74 deceased subjects (of 216 trial participants) were analyzed. Forty-six of 47 neuritic beta-amyloid-positive cases were read as PET positive, and 24 of 27 neuritic beta-amyloid plaque-negative cases were read as PET negative (sensitivity 97.9% [95% confidence interval or CI 93.8-100%], specificity 88.9% [95% CI 77.0-100%]). In a subgroup, a regional tissue-scan matched analysis was performed. In areas known to strongly accumulate beta-amyloid plaques, sensitivity and specificity were 82% to 90%, and 86% to 95%, respectively. Conclusions: Florbetaben PET shows high sensitivity and specificity for the detection of histopathology-confirmed neuritic beta-amyloid plaques and may thus be a valuable adjunct to clinical diagnosis, particularly for the exclusion of AD. (C) 2015 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer'sAssociation. C1 [Sabri, Osama; Barthel, Henryk] Univ Leipzig, Dept Nucl Med, D-04109 Leipzig, Germany. [Sabbagh, Marwan N.; Beach, Thomas G.] Banner Sun Hlth Res Inst, Sun City, AZ USA. [Seibyl, John] Mol Neuroimaging LLC, New Haven, CT USA. [Akatsu, Hiroyasu] Fukushimura Hosp, Toyohashi, Aichi, Japan. [Akatsu, Hiroyasu] Nagoya City Univ, Grad Sch Med Sci, Dept Community Based Med, Nagoya, Aichi, Japan. [Akatsu, Hiroyasu] Nagoya City Univ, Grad Sch Med Sci, Dept Neurol, Nagoya, Aichi, Japan. [Ouchi, Yasuomi] Hamamatsu Univ Sch Med, Med Photon Res Ctr, Dept Biofunct Imaging, Hamamatsu, Shizuoka 4313192, Japan. [Senda, Kohei] Koseikai Hosp, Toyohashi, Aichi, Japan. [Murayama, Shigeo] Tokyo Metropolitan Geriatr Hosp, Dept Neurol & Neuropathol, Tokyo 173, Japan. [Murayama, Shigeo] Inst Gerontol, Tokyo, Japan. [Murayama, Shigeo; Ishii, Kenji; Takao, Masaki] Tokyo Metropolitan Inst Gerontol, Tokyo, Japan. [Takao, Masaki] Mihara Mem Hosp, Isesaki, Japan. [Rowe, Christopher C.] Univ Melbourne, Dept Mol Imaging, Austin Hlth, Melbourne, Vic, Australia. [Leverenz, James B.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Leverenz, James B.] Univ Washington, Seattle, WA 98195 USA. [Ghetti, Bernardino] Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA. [Ironside, James W.] Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland. [Catafau, Ana M.; Stephens, Andrew W.; Mueller, Andre; Koglin, Norman] Piramal Imaging GmbH, Berlin, Germany. [Hoffmann, Anja; Roth, Katrin; Reininger, Cornelia] Bayer Pharma AG, Berlin, Germany. [Schulz-Schaeffer, Walter J.] Univ Med Ctr Gottingen, Dept Neuropathol, Gottingen, Germany. RP Sabri, O (reprint author), Univ Leipzig, Dept Nucl Med, D-04109 Leipzig, Germany. EM osama.sabri@medizin.uni-leipzig.de OI Ironside, James/0000-0001-5869-2108 FU Piramal Imaging S.A; Bayer Pharma AG, Berlin (Germany); Piramal Imaging S.A., Matran (Switzerland) FX Medical writing support was provided by Dan Booth (Bioscript Medical, London, UK) and funded by Piramal Imaging S.A. Additional statistical analysis was carried out by Santi Bullich (Piramal Imaging GmbH).; The trial was funded by Bayer Pharma AG, Berlin (Germany), and Piramal Imaging S.A., Matran (Switzerland). Bayer Pharma AG was involved in the design of the study; Bayer Pharma AG and Piramal Imaging SA were involved in the conduct of the study; collection, management, analysis, and interpretation of the data; and in the preparation, review, and approval of the manuscript. NR 31 TC 36 Z9 39 U1 1 U2 14 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 2015 VL 11 IS 8 BP 964 EP 974 DI 10.1016/j.jalz.2015.02.004 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA CQ9DT UT WOS:000360912300008 PM 25824567 ER PT J AU Dodson, M Redmann, M Rajasekaran, NS Darley-Usmar, V Zhang, JH AF Dodson, Matthew Redmann, Matthew Rajasekaran, Namakkal S. Darley-Usmar, Victor Zhang, Jianhua TI KEAP1-NRF2 signalling and autophagy in protection against oxidative and reductive proteotoxicity SO BIOCHEMICAL JOURNAL LA English DT Review DE antioxidants; autophagy; KEAP1-NRF2; mitophagy; p62; redox signalling ID TRANSCRIPTION FACTOR NRF2; CUL3-BASED E3 LIGASE; ANTIOXIDANT RESPONSE; NEURODEGENERATIVE DISEASE; PROTEIN AGGREGATION; SELECTIVE AUTOPHAGY; OXIDIZED PROTEINS; REDOX REGULATION; NUCLEAR EXPORT; MOUSE MODEL AB Maintaining cellular redox status to allow cell signalling to occur requires modulation of both the controlled production of oxidants and the thiol-reducing networks to allow specific regulatory post-translational modification of protein thiols. The oxidative stress hypothesis captured the concept that overproduction of oxidants can be proteotoxic, but failed to predict the recent finding that hyperactivation of the KEAP1-NRF2 system also leads to proteotoxicity. Furthermore, sustained activation of thiol redox networks by KEAP1-NRF2 induces a reductive stress, by decreasing the lifetime of necessary oxidative post-translational modifications required for normal metabolism or cell signalling. In this context, it is now becoming clear why antioxidants or hyperactivation of antioxidant pathways with electrophilic therapeutics can be deleterious. Furthermore, it suggests that the autophagy-lysosomal pathway is particularly important in protecting the cell against redox-stress-induced proteotoxicity, since it can degrade redox-damaged proteins without causing aberrant changes to the redox network needed for metabolism or signalling. In this context, it is important to understand: (i) how NRF2-mediated redox signalling, or (ii) the autophagy-mediated antioxidant/reductant pathways sense cellular damage in the context of cellular pathogenesis. Recent studies indicate that the modification of protein thiols plays an important role in the regulation of both the KEAP1-NRF2 and autophagy pathways. In the present review, we discuss evidence demonstrating that the KEAP1-NRF2 pathway and autophagy act in concert to combat the deleterious effects of proteotoxicity. These findings are discussed with a special emphasis on their impact on cardiovascular disease and neurodegeneration. C1 [Dodson, Matthew; Redmann, Matthew; Rajasekaran, Namakkal S.; Darley-Usmar, Victor; Zhang, Jianhua] Univ Alabama Birmingham, Ctr Free Rad Biol, Birmingham, AL 35294 USA. [Dodson, Matthew; Redmann, Matthew; Rajasekaran, Namakkal S.; Darley-Usmar, Victor; Zhang, Jianhua] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35233 USA. [Zhang, Jianhua] Birmingham VA Med Ctr, Dept Vet Affairs, Birmingham, AL 35233 USA. RP Zhang, JH (reprint author), Univ Alabama Birmingham, Ctr Free Rad Biol, 901 19th St South, Birmingham, AL 35294 USA. EM zhanja@uab.edu OI Zhang, Jianhua/0000-0002-2128-9574 FU National Institutes of Health [NIHR01-NS064090, NIHR01-HL118067, NIHR03-AG042860]; American Heart Association [0865015F] FX This work was supported by the National Institutes of Health [grant numbers NIHR01-NS064090 (to J.Z.), NIHR01-HL118067 (to N.S.R.), and NIHR03-AG042860 (to N.S.R.)] and the American Heart Association [grant number AHA-BGIA# 0865015F (to N.S.R.)]. NR 118 TC 20 Z9 23 U1 7 U2 26 PU PORTLAND PRESS LTD PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND SN 0264-6021 EI 1470-8728 J9 BIOCHEM J JI Biochem. J. PD AUG 1 PY 2015 VL 469 BP 347 EP 355 DI 10.1042/BJ20150568 PN 3 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CR0ZW UT WOS:000361053400002 PM 26205490 ER PT J AU Inamoto, Y Shah, NN Savani, BN Shaw, BE Abraham, AA Ahmed, IA Akpek, G Atsuta, Y Baker, KS Basak, GW Bitan, M DeFilipp, Z Gregory, TK Greinix, HT Hamadani, M Hamilton, BK Hayashi, RJ Jacobsohn, DA Kamble, RT Kasow, KA Khera, N Lazarus, HM Malone, AK Lupo-Stanghellini, MT Margossian, SP Muffly, LS Norkin, M Ramanathan, M Salooja, N Schoemans, H Wingard, JR Wirk, B Wood, WA Yong, A Duncan, CN Flowers, MED Majhail, NS AF Inamoto, Y. Shah, N. N. Savani, B. N. Shaw, B. E. Abraham, A. A. Ahmed, I. A. Akpek, G. Atsuta, Y. Baker, K. S. Basak, G. W. Bitan, M. DeFilipp, Z. Gregory, T. K. Greinix, H. T. Hamadani, M. Hamilton, B. K. Hayashi, R. J. Jacobsohn, D. A. Kamble, R. T. Kasow, K. A. Khera, N. Lazarus, H. M. Malone, A. K. Lupo-Stanghellini, M. T. Margossian, S. P. Muffly, L. S. Norkin, M. Ramanathan, M. Salooja, N. Schoemans, H. Wingard, J. R. Wirk, B. Wood, W. A. Yong, A. Duncan, C. N. Flowers, M. E. D. Majhail, N. S. TI Secondary solid cancer screening following hematopoietic cell transplantation SO BONE MARROW TRANSPLANTATION LA English DT Review ID BONE-MARROW-TRANSPLANTATION; LONG-TERM SURVIVORS; INCREASED RISK; TESTICULAR CANCER; BREAST-CANCER; ENDOMETRIAL CARCINOMA; MALIGNANT NEOPLASMS; CHILDHOOD-CANCER; HPV VACCINATION; CERVICAL-CANCER AB Hematopoietic stem cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers, particularly beyond 5 years after HCT and without reaching a plateau overtime. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to facilitate implementation of cancer screening appropriate to HCT recipients. The working group reviewed guidelines and methods for cancer screening applicable to the general population and reviewed the incidence and risk factors for secondary cancers after HCT. A consensus approach was used to establish recommendations for individual secondary cancers. The most common sites include oral cavity, skin, breast and thyroid. Risks of cancers are increased after HCT compared with the general population in skin, thyroid, oral cavity, esophagus, liver, nervous system, bone and connective tissues. Myeloablative TBI, young age at HCT, chronic GVHD and prolonged immunosuppressive treatment beyond 24 months were well-documented risk factors for many types of secondary cancers. All HCT recipients should be advised of the risks of secondary cancers annually and encouraged to undergo recommended screening based on their predisposition. Here we propose guidelines to help clinicians in providing screening and preventive care for secondary cancers among HCT recipients. C1 [Inamoto, Y.] Natl Canc Ctr, Div Hematopoiet Stem Cell Transplantat, Tokyo, Japan. [Shah, N. N.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Savani, B. N.] Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol, Nashville, TN USA. [Shaw, B. E.; Hamadani, M.] Med Coll Wisconsin, Dept Med, CIBMTR, Milwaukee, WI 53226 USA. [Abraham, A. A.; Jacobsohn, D. A.] Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Div Blood & Marrow Transplantat, Washington, DC 20010 USA. [Ahmed, I. A.] Childrens Mercy Hosp & Clin, Dept Hematol Oncol & Bone Marrow Transplantat, Kansas City, MO USA. [Akpek, G.] Banner MD Anderson Canc Ctr, Sect Hematol Oncol, Gilbert, AZ USA. [Atsuta, Y.] Japanese Data Ctr Hematopoiet Cell Transplantat, Nagoya, Aichi, Japan. [Atsuta, Y.] Nagoya Univ, Grad Sch Med, Nagoya, Aichi 4648601, Japan. [Baker, K. S.; Flowers, M. E. D.] Fred Hutchinson Canc Res Ctr, Clin Res Div, Seattle, WA 98104 USA. [Basak, G. W.] Med Univ Warsaw, Dept Hematol Oncol & Internal Dis, Warsaw, Poland. [Bitan, M.] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Pediat Hematol Oncol, IL-69978 Tel Aviv, Israel. [DeFilipp, Z.] Emory Univ, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA. [Gregory, T. K.] Presbyterian St Lukes Med Ctr, Colorado Blood Canc Inst, Denver, CO USA. [Greinix, H. T.] Med Univ Vienna, Dept Internal Med 1, Bone Marrow Transplantat Unit, Vienna, Austria. [Hamilton, B. K.; Majhail, N. S.] Cleveland Clin, Taussig Canc Inst, Blood & Marrow Transplant Program, Cleveland, OH 44106 USA. [Hayashi, R. J.] Washington Univ, Sch Med, Dept Pediat, Div Pediat Hematol Oncol, St Louis, MO 63110 USA. [Kamble, R. T.] Baylor Coll Med, Div Hematol & Oncol, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [Kasow, K. A.] Univ N Carolina, Dept Pediat, Div Hematol Oncol, Chapel Hill, NC USA. [Khera, N.] Mayo Clin, Dept Hematol Oncol, Phoenix, AZ USA. [Lazarus, H. M.] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Cleveland, OH USA. [Malone, A. K.] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA. [Lupo-Stanghellini, M. T.] IRCCS San Raffaele Sci Inst, Unit Hematol & Bone Marrow Transplantat, Milan, Italy. [Margossian, S. P.; Duncan, C. N.] Boston Childrens Hosp, Dept Pediat Oncol, Boston, MA USA. [Margossian, S. P.; Duncan, C. N.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Muffly, L. S.] Stanford Univ, Div Blood & Marrow Transplantat, Stanford, CA 94305 USA. [Norkin, M.; Wingard, J. R.] Univ Florida, Dept Med, Div Hematol & Oncol, Gainesville, FL USA. [Ramanathan, M.] Univ Massachusetts, Mem Med Ctr, Dept Med, Div Hematol & Oncol, Worcester, MA USA. [Salooja, N.] Univ London Imperial Coll Sci Technol & Med, London, England. [Schoemans, H.] Univ Hosp Leuven, Leuven, Belgium. [Wirk, B.] SUNY Stony Brook, Med Ctr, Dept Internal Med, Stony Brook, NY 11794 USA. [Wood, W. A.] Univ N Carolina, Dept Med, Div Hematol Oncol, Chapel Hill, NC USA. [Yong, A.] SA Pathol, Royal Adelaide Hosp, Adelaide, SA, Australia. [Yong, A.] Univ Adelaide, Sch Med, Adelaide, SA, Australia. RP Majhail, NS (reprint author), Cleveland Clin, Taussig Canc Inst, Blood & Marrow Transplant Program, 9500 Euclid Ave,R35, Cleveland, OH 44195 USA. EM majhain@ccf.org FU NCI NIH HHS [U24 CA076518, U24-CA76518]; NHLBI NIH HHS [U01 HL069294, 5U01HL069294]; PHS HHS [HHSH234200637015C] NR 85 TC 11 Z9 11 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD AUG PY 2015 VL 50 IS 8 BP 1013 EP 1023 DI 10.1038/bmt.2015.63 PG 11 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA CR2MM UT WOS:000361164200001 PM 25822223 ER PT J AU Mohty, M Richardson, PG McCarthy, PL Attal, M AF Mohty, M. Richardson, P. G. McCarthy, P. L. Attal, M. TI Consolidation and maintenance therapy for multiple myeloma after autologous transplantation: where do we stand? SO BONE MARROW TRANSPLANTATION LA English DT Review ID STEM-CELL TRANSPLANTATION; THALIDOMIDE PLUS DEXAMETHASONE; RANDOMIZED PHASE-3 TRIAL; MINIMAL RESIDUAL DISEASE; INDUCTION TREATMENT; COMPLETE RESPONSE; VTD INDUCTION; FOLLOW-UP; BORTEZOMIB; SURVIVAL AB Novel agents including proteasome inhibitors and immunomodulatory drugs are now routinely utilized as part of the induction regimen before transplantation and this has resulted in substantial improvements in the depth of response achieved before transplant. Given that depth of response is prognostic for overall outcome, a number of studies have been conducted or are ongoing to investigate the use of novel agents as consolidation and maintenance therapy after transplant. Most clinical trials have reported after consolidation and maintenance therapy an increased PFS and even overall survival in some of them. The use of post-autologous stem cell transplant consolidation and maintenance is an increasingly attractive concept. However, some side effects could be observed with such long-term therapy and many open questions are still under debate. The decision to administer consolidation and/or maintenance therapy will likely need to be guided by the individual patient situation. This review aims to analyze the currently available research evidence in this field. C1 [Mohty, M.] Hop St Antoine, AP HP, Serv Hematol Clin & Therapie Cellulaire, F-75571 Paris, France. [Mohty, M.] Univ Paris 06, Paris, France. [Mohty, M.] INSERM, UMRs 938, Paris, France. [Richardson, P. G.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA 02115 USA. [McCarthy, P. L.] Roswell Pk Canc Inst, Blood & Marrow Transplant Program, Buffalo, NY 14263 USA. [Attal, M.] Hop Purpan, Hematol Clin, Toulouse, France. [Attal, M.] IUCT, Toulouse, France. RP Mohty, M (reprint author), Hop St Antoine, AP HP, Serv Hematol Clin & Therapie Cellulaire, 184 Rue Faubourg St Antoine, F-75571 Paris, France. EM mohamad.mohty@inserm.fr NR 45 TC 7 Z9 7 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD AUG PY 2015 VL 50 IS 8 BP 1024 EP 1029 DI 10.1038/bmt.2015.83 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA CR2MM UT WOS:000361164200002 PM 25893452 ER PT J AU Goyal, SD Zhang, MJ Wang, HL Akpek, G Copelan, EA Freytes, C Gale, RP Hamadani, M Inamoto, Y Kamble, RT Lazarus, HM Marks, DI Nishihori, T Olsson, RF Reshef, R Ritchie, DS Saber, W Savani, BN Seber, A Shea, TC Tallman, MS Wirk, B Bunjes, DW Devine, SM de Lima, M Weisdorf, DJ Uy, GL AF Goyal, S. D. Zhang, M-J Wang, H-L Akpek, G. Copelan, E. A. Freytes, C. Gale, R. P. Hamadani, M. Inamoto, Y. Kamble, R. T. Lazarus, H. M. Marks, D. I. Nishihori, T. Olsson, R. F. Reshef, R. Ritchie, D. S. Saber, W. Savani, B. N. Seber, A. Shea, T. C. Tallman, M. S. Wirk, B. Bunjes, D. W. Devine, S. M. de Lima, M. Weisdorf, D. J. Uy, G. L. CA Ctr Int Blood Marrow TI Allogeneic hematopoietic cell transplant for AML: no impact of pre-transplant extramedullary disease on outcome SO BONE MARROW TRANSPLANTATION LA English DT Article ID ACUTE MYELOID-LEUKEMIA; LONG-TERM SURVIVAL; RISK-FACTORS; RELAPSE; REMISSION; SARCOMA; MARROW AB The impact of extramedullary disease (EMD) in AML on the outcomes of allogeneic hematopoietic cell transplantation (alloHCT) is unknown. Using data from the Center for International Blood and Marrow Transplant Research, we compared the outcomes of patients who had EMD of AML at any time before transplant, with a cohort of AML patients without EMD. We reviewed data from 9797 AML patients including 814 with EMD from 310 reporting centers and 44 different countries, who underwent alloHCT between and 1995 and 2010. The primary outcome was overall survival (OS) after alloHCT. Secondary outcomes included leukemia-free survival (LFS), relapse rate and treatment-related mortality (TRM). In a multivariate analysis, the presence of EMD did not affect either OS (hazard ratio 1.00, 95% confidence interval (Cl) 0.91-1.09), LFS (0.98, 0.89-1.09), TRM (relative risk 0.92, 95% CI 0.80-1.16, P=0.23) or relapse (relative risk= 1.03, 95% CI, 0.92-1.16; P=0.62). Furthermore, the outcome of patients with EMD was not influenced by the location, timing of EMD, or intensity of conditioning regimen. The presence of EMD in AML does not affect transplant outcomes and should not be viewed as an independent adverse prognostic feature. C1 [Goyal, S. D.] St Louis Univ, Med Ctr, St Louis, MO USA. [Zhang, M-J; Wang, H-L; Hamadani, M.; Saber, W.] Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Zhang, M-J] Med Coll Wisconsin, Div Biostat, Inst Hlth & Soc, Milwaukee, WI 53226 USA. [Akpek, G.] Banner MD Anderson Canc Ctr, Hematol Oncol Sect, Gilbert, AZ USA. [Copelan, E. A.] Carolinas HealthCare Syst, Levine Canc Inst, Dept Hematol Oncol & Blood Disorders, Charlotte, NC USA. [Freytes, C.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Freytes, C.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Gale, R. P.] Univ London Imperial Coll Sci Technol & Med, Dept Med, Hematol Res Ctr, Div Expt Med, London, England. [Inamoto, Y.] Natl Canc Ctr, Tokyo, Japan. [Kamble, R. T.] Baylor Coll Med, Div Hematol & Oncol, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [Lazarus, H. M.; de Lima, M.] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Cleveland, OH USA. [Marks, D. I.] Univ Hosp Bristol NHS Trust, Pediat Bone Marrow Transplant, Bristol, Avon, England. [Nishihori, T.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL 33612 USA. [Olsson, R. F.] Karolinska Inst, Dept Lab Med, Div Therapeut Immunol, Stockholm, Sweden. [Olsson, R. F.] Uppsala Univ, Ctr Clin Res Sormland, Uppsala, Sweden. [Reshef, R.] Univ Penn, Med Ctr, Dept Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Ritchie, D. S.] Royal Melbourne Hosp, Melbourne, Vic, Australia. [Savani, B. N.] Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol, Nashville, TN USA. [Seber, A.] Hosp Samaritano, Sao Paulo, Brazil. [Shea, T. C.] Univ North Carolina Hlth Care, Dept Med, Div Hematol & Oncol, Chapel Hill, NC USA. [Tallman, M. S.] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, New York, NY 10021 USA. [Wirk, B.] SUNY Stony Brook, Dept Internal Med, Med Ctr, Stony Brook, NY 11794 USA. [Bunjes, D. W.] Univ Ulm Klinikum, Dept Internal Med 3, Ulm, Germany. [Devine, S. M.] Ohio State Univ, Ctr Comprehens Canc, Dept Internal Med, Columbus, OH 43210 USA. [Weisdorf, D. J.] Univ Minnesota, Dept Med, Med Ctr, Div Hematol Oncol & Transplantat, Minneapolis, MN 55455 USA. [Uy, G. L.] Washington Univ, Dept Med, Sch Med, St Louis, MO 63110 USA. RP Uy, GL (reprint author), Washington Univ, Dept Med, Sch Med, 660 South Euclid Ave,Campus Box 8007, St Louis, MO 63110 USA. EM guy@dom.wustl.edu FU NCI NIH HHS [U24 CA076518, K23 CA140707, U24-CA076518]; NHLBI NIH HHS [5U10HL069294, U10 HL069294]; PHS HHS [HHSH250201200016C] NR 17 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD AUG PY 2015 VL 50 IS 8 BP 1057 EP 1062 DI 10.1038/bmt.2015.82 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA CR2MM UT WOS:000361164200005 PM 25915806 ER PT J AU EI-Jawahri, A Traeger, L Kuzmuk, K Eusebio, J Vandusen, H Keenan, T Shin, J Gallagher, ER Greer, JA Pirl, WF Jackson, VA Ballen, KK Spitzer, TR Graubert, TA McAfee, S Dey, B Chen, YBA Temel, JS AF EI-Jawahri, A. Traeger, L. Kuzmuk, K. Eusebio, J. Vandusen, H. Keenan, T. Shin, J. Gallagher, E. R. Greer, J. A. Pirl, W. F. Jackson, V. A. Ballen, K. K. Spitzer, T. R. Graubert, T. A. McAfee, S. Dey, B. Chen, Y-B A. Temel, J. S. TI Prognostic understanding, quality of life and mood in patients undergoing hematopoietic stem cell transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article ID BONE-MARROW-TRANSPLANTATION; LUNG-CANCER; FAMILY CAREGIVERS; PREFERENCES; HEALTH; CHEMOTHERAPY; CARE; COMMUNICATION; PHYSICIANS; THERAPY AB Little is known about how patients undergoing hematopoietic stem cell transplantation (HCT) and their family caregivers (FC) perceive their prognosis. We examined prognostic understanding in patients undergoing HCT and their FC and its relationship with quality of life (QOL) and mood. We conducted a longitudinal study of patients (and FC) hospitalized for HCT. We used a questionnaire to measure participants' prognostic understanding and asked the oncologists to estimate patients' prognosis prior to HCT. We assessed QOL and mood weekly and evaluated the relationship between prognostic understanding, and QOL and mood using multivariable linear mixed models. We enrolled 90 patients undergoing (autologous (n=30), myeloablative (n=30) or reduced intensity allogeneic (n=30)) HCT. About 88.9% of patients and 87.1% of FC reported it is 'extremely' or 'very' important to know about prognosis. However, 77.6% of patients and 71.7% of FC reported a discordance and more optimistic prognostic perception compared to the oncologist (P< 0.0001). Patients with a concordant prognostic understanding with their oncologists reported worse QOL (beta = -9.4, P=0.01) and greater depression at baseline (beta = 1.7, P=0.02) and over time ((beta = 1.2, P < 0.0001). Therefore, Interventions are needed to improve prognostic understanding, while providing patients with adequate psychological support. C1 [EI-Jawahri, A.; Traeger, L.; Kuzmuk, K.; Eusebio, J.; Vandusen, H.; Keenan, T.; Shin, J.; Gallagher, E. R.; Greer, J. A.; Pirl, W. F.; Jackson, V. A.; Ballen, K. K.; Spitzer, T. R.; Graubert, T. A.; McAfee, S.; Dey, B.; Chen, Y-B A.; Temel, J. S.] Massachusetts Gen Hosp, Dept Hematol Oncol, Bone Marrow Transplant Program, Boston, MA 02114 USA. [EI-Jawahri, A.; Traeger, L.; Eusebio, J.; Vandusen, H.; Keenan, T.; Shin, J.; Gallagher, E. R.; Greer, J. A.; Pirl, W. F.; Jackson, V. A.; Ballen, K. K.; Spitzer, T. R.; Graubert, T. A.; McAfee, S.; Dey, B.; Chen, Y-B A.; Temel, J. S.] Harvard Univ, Sch Med, Boston, MA USA. RP EI-Jawahri, A (reprint author), Massachusetts Gen Hosp, Dept Hematol Oncol, Bone Marrow Transplant Program, 55 Fruit St,Cox 120, Boston, MA 02114 USA. EM ael-jawahri@partners.org OI Graubert, Timothy/0000-0002-7710-1171 NR 34 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD AUG PY 2015 VL 50 IS 8 BP 1119 EP 1124 DI 10.1038/bmt.2015.113 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA CR2MM UT WOS:000361164200015 ER PT J AU Arya, R Sarkissian, T Tan, Y White, K AF Arya, R. Sarkissian, T. Tan, Y. White, K. TI Neural stem cell progeny regulate stem cell death in a Notch and Hox dependent manner SO CELL DEATH AND DIFFERENTIATION LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; DROSOPHILA-MELANOGASTER; NEUROBLAST APOPTOSIS; SEGMENTATION CLOCK; GENE-EXPRESSION; GLIAL-CELLS; PROLIFERATION; SURVIVAL; REAPER; REGION AB Cell death is a prevalent, well-controlled and fundamental aspect of development, particularly in the nervous system. In Drosophila, specific neural stem cells are eliminated by apoptosis during embryogenesis. In the absence of apoptosis, these stem cells continue to divide, resulting in a dramatically hyperplastic central nervous system and adult lethality. Although core cell death pathways have been well described, the spatial, temporal and cell identity cues that activate the cell death machinery in specific cells are largely unknown. We identified a cis-regulatory region that controls the transcription of the cell death activators reaper, grim and sickle exclusively in neural stem cells. Using a reporter generated from this regulatory region, we found that Notch activity is required for neural stem cell death. Notch regulates the expression of the abdominalA homeobox protein, which provides important spatial cues for death. Importantly, we show that pro-apoptotic Notch signaling is activated by the Delta ligand expressed on the neighboring progeny of the stem cell. Thus we identify a previously undescribed role for progeny in regulating the proper developmental death of their parental stem cells. C1 [Arya, R.; Sarkissian, T.; Tan, Y.; White, K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, CBRC, Charlestown, MA 02129 USA. RP White, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, CBRC, Bldg 149,13th St, Charlestown, MA 02129 USA. EM kristin.white@mgh.harvard.edu FU MGH Fund for Medical Discovery fellowship; [R01GM55568] FX This work was funded in part by R01GM55568 (KW) and an MGH Fund for Medical Discovery fellowship (RA). RA and KW designed the experiments, RA produced all of the data, with assistance from TS. YT conducted some of the original screen. KW directed the research and prepared the manuscript. We thank Ritu Tomar, Francisca Rodriguez and Hsiao-Yu Huang for technical assistance, Chris Doe and the Developmental Studies Hybridoma Bank for antibodies, Iswar Hariharan, Yacine Graba, Spyros Artavanis-Tsakonas and Kazuya Hori and the Bloomington Stock Center for fly strains, Liz Perkins and the TRiP (Boston, MA, USA) for RNAi lines, Ila Joshi and Katia Georgopoulos for comments on the manuscript and Lei Zhou for information about unpublished ChIP analyses. NR 58 TC 4 Z9 4 U1 3 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 EI 1476-5403 J9 CELL DEATH DIFFER JI Cell Death Differ. PD AUG PY 2015 VL 22 IS 8 BP 1378 EP 1387 DI 10.1038/cdd.2014.235 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CM3QX UT WOS:000357599500014 PM 25633198 ER PT J AU Rattner, DW AF Rattner, David W. TI Looking back and forward at natural orifice translumenal endoscopic surgery SO CIRUGIA ESPANOLA LA Spanish DT Editorial Material C1 Massachusetts Gen Hosp, Chief Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. RP Rattner, DW (reprint author), Massachusetts Gen Hosp, Chief Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. EM drattner@partners.org NR 6 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER DOYMA SL PI BARCELONA PA TRAVESERA DE GARCIA, 17-21, BARCELONA, 08021, SPAIN SN 0009-739X EI 1578-147X J9 CIR ESPAN JI Cir. Espan. PD AUG-SEP PY 2015 VL 93 IS 7 BP 421 EP 422 DI 10.1016/j.ciresp.2015.02.001 PG 2 WC Surgery SC Surgery GA CQ9WE UT WOS:000360965100009 PM 25778406 ER PT J AU Lieberman, J AF Lieberman, Judy TI Manipulating the in vivo immune response by targeted gene knockdown SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID APTAMER-SIRNA CHIMERAS; RNA APTAMER; T-CELLS; OLIGONUCLEOTIDE APTAMERS; 4-1BB COSTIMULATION; HIV TRANSMISSION; LYMPHOMA-CELLS; FLOW-CYTOMETRY; TUMOR-IMMUNITY; LIVE CELLS AB Aptamers, nucleic acids selected for high affinity binding to proteins, can be used to activate or antagonize immune mediators or receptors in a location and cell-type specific manner and to enhance antigen presentation. They can also be linked to other molecules (other aptamers, siRNAs or miRNAs, proteins, toxins) to produce multifunctional compounds for targeted immune modulation in vivo. Aptamer-siRNA chimeras (AsiCs) that induce efficient cell-specific knockdown in immune cells in vitro and in vivo can be used as an immunological research tool or potentially as an immunomodulating therapeutic. C1 [Lieberman, Judy] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, 200 Longwood Ave, Boston, MA 02115 USA. EM judy.lieberman@childrens.harvard.edu FU NIH [AI090671] FX This work was supported by NIH AI090671 (J.L.). I thank Eli Gilboa, Paloma Giangrande and laboratory members for many useful discussions on applications of aptamer technology to immunology research and therapy. NR 81 TC 2 Z9 2 U1 1 U2 12 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 2015 VL 35 BP 63 EP 72 DI 10.1016/j.coi.2015.06.005 PG 10 WC Immunology SC Immunology GA CR1HB UT WOS:000361074400011 PM 26149459 ER PT J AU Alvarez-Breckenridge, CA Choi, BD Suryadevara, CM Chiocca, A AF Alvarez-Breckenridge, Christopher A. Choi, Bryan D. Suryadevara, Carter M. Chiocca, Antonio TI Potentiating oncolytic viral therapy through an understanding of the initial immune responses to oncolytic viral infection SO CURRENT OPINION IN VIROLOGY LA English DT Article ID VESICULAR STOMATITIS-VIRUS; NATURAL-KILLER-CELLS; REGULATORY T-CELLS; POSTOPERATIVE METASTATIC-DISEASE; IN-VIVO; HEPATOCELLULAR-CARCINOMA; CANCER-IMMUNOTHERAPY; PROTECTIVE IMMUNITY; GLIOMA VIROTHERAPY; CYCLOPHOSPHAMIDE AB Despite the challenge of implementing oncolytic viral therapy into mainstream clinical use, the obstacles of early clinical trials have outlined numerous areas requiring additional investigation. In particular, the role of innate and adaptive immunity has received significant attention in this context. It is increasingly clear that a one-sided approach of either immune suppression or robust immune cell activation is not the answer for clinical success. Rather, recent studies are increasingly demonstrating the delicate balance between both anti-viral immune suppression and immune mediated tumor killing. In this review we focus on aspects of innate immune cell activation following oncolytic viral infection and how this response has the potential of bridging to the broader goal of viral mediated imunotherapy. C1 [Alvarez-Breckenridge, Christopher A.; Choi, Bryan D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Suryadevara, Carter M.] Duke Univ, Med Ctr, Dept Surg, Div Neurosurg,Duke Brain Tumor Immunotherapy Prog, Durham, NC 27710 USA. [Chiocca, Antonio] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Neurosurg, Boston, MA 02115 USA. RP Chiocca, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Neurosurg, 44 Binney St, Boston, MA 02115 USA. EM EAChiocca@partners.org FU NCI [P01CA163205] FX These studies were supported by NCI P01CA163205. NR 61 TC 1 Z9 1 U1 2 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1879-6257 J9 CURR OPIN VIROL JI Curr. Opin. Virol. PD AUG PY 2015 VL 13 BP 25 EP + DI 10.1016/j.coviro.2015.03.015 PG 8 WC Virology SC Virology GA CR1HA UT WOS:000361074300007 PM 25846988 ER PT J AU Bind, MAC Coull, BA Peters, A Baccarelli, AA Tarantini, L Cantone, L Vokonas, PS Koutrakis, P Schwartz, JD AF Bind, Marie-Abele C. Coull, Brent A. Peters, Annette Baccarelli, Andrea A. Tarantini, Letizia Cantone, Laura Vokonas, Pantel S. Koutrakis, Petros Schwartz, Joel D. TI Beyond the Mean: Quantile Regression to Explore the Association of Air Pollution with Gene-Specific Methylation in the Normative Aging Study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; NITRIC-OXIDE SYNTHASE; DNA METHYLATION; CARDIOVASCULAR-DISEASE; PARTICULATE MATTER; TISSUE FACTOR; OXIDATIVE STRESS; EXPOSURE; PROMOTER AB BACKGROUND: Air pollution has been related to mean changes in outcomes, including DNA methylation. However, mean regression analyses may not capture associations that occur primarily in the tails of the outcome distribution. OBJECTIVES: In this study, we examined whether the association between particulate air pollution and DNA methylation differs across quantiles of the methylation distribution. We focused on methylation of candidate genes related to coagulation and inflammation: coagulation factor III (F3), intercellular adhesion molecule 1 (ICAM-1), interferon gamma (IFN-gamma), interleukin-6 (IL-6), and toll-like receptor 2 (TRL-2). METHODS: We measured gene-specific blood DNA methylation repeatedly in 777 elderly men participating in the Normative Aging Study (1999-2010). We fit quantile regressions for longitudinal data to investigate whether the associations of particle number, PM2.5 (diameter <= 2.5 mu m) black carbon, and PM2.5 mass concentrations (4-week moving average) with DNA methylation [expressed as the percentage of methylated cytosines over the sum of methylated and unmethylated cytosines at position 5 (% 5mC)] varied across deciles of the methylation distribution. We reported the quantile regression coefficients that corresponded to absolute differences in DNA methylation (expressed in % 5mC) associated with an interquartile range increase in air pollution concentration. RESULTS: Interquartile range increases in particle number, PM2.5 black carbon, and PM2.5 mass concentrations were associated with significantly lower methylation in the lower tails of the IFN-gamma and ICAM-1 methylation distributions. For instance, a 3.4-mu g/m(3) increase in PM2.5 mass concentration was associated with a 0.18% 5mC (95% CI: -0.30, -0.06) decrease on the 20th percentile of ICAM-1 methylation, but was not significantly related to the 80th percentile (estimate: 0.07% 5mC, 95% CI: -0.09, 0.24). CONCLUSIONS: In our study population of older men, air pollution exposures were associated with a left shift in the lower tails of the IFN-gamma and ICAM-1 methylation distributions. C1 [Bind, Marie-Abele C.; Peters, Annette; Baccarelli, Andrea A.; Koutrakis, Petros; Schwartz, Joel D.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Bind, Marie-Abele C.; Coull, Brent A.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Peters, Annette] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol, Neuherberg, Germany. [Tarantini, Letizia; Cantone, Laura] Univ Milan, Ctr Mol & Genet Epidemiol, Dept Clin Sci & Community Hlth, Milan, Italy. [Tarantini, Letizia; Cantone, Laura] Fdn Ca Granda, IRCCS, Osped Maggiore Policlin, Milan, Italy. [Vokonas, Pantel S.] VA Boston Healthcare Syst, VA Normat Aging Study, Boston, MA USA. [Vokonas, Pantel S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. RP Bind, MAC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Landmark Ctr, 401 Pk Dr,Suite 415, Boston, MA 02115 USA. EM ma.bind@mail.harvard.edu RI Peters, Annette/A-6117-2011; OI Baccarelli, Andrea/0000-0002-3436-0640; Cantone, Laura/0000-0003-3660-129X; Peters, Annette/0000-0001-6645-0985 FU U.S. Environmental Protection Agency (EPA) [RD-827353, RD-832416]; National Institute of Environmental Health Sciences (NIEHS)/National Institutes of Health [RO1-ES015172, 2RO1-ES015172, ES014663, ES00002, PO1-ES008925]; Harvard-U.S. EPA Clean Air Center (CLARC) [RD-83479801]; Cooperative Studies Program/Epidemiology Research and Information Center of the U.S. Department of Veterans Affairs a component of the Massachusetts Veterans Epidemiology Research and Information Center, Boston, Massachusetts FX This study was supported by U.S. Environmental Protection Agency (EPA) grants RD-827353 and RD-832416; National Institute of Environmental Health Sciences (NIEHS)/National Institutes of Health grants RO1-ES015172, 2RO1-ES015172, ES014663, ES00002, PO1-ES008925; and Harvard-U.S. EPA Clean Air Center (CLARC) grant RD-83479801. The VA 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, Massachusetts. NR 33 TC 2 Z9 2 U1 2 U2 19 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD AUG PY 2015 VL 123 IS 8 BP 759 EP 765 DI 10.1289/ehp.1307824 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA CQ6CX UT WOS:000360693100016 PM 25769179 ER PT J AU Baxi, SM Lakin, JR AF Baxi, Sanjiv M. Lakin, Joshua R. TI Preoperative Testing-A Bridge to Nowhere A Teachable Moment SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID ISCHEMIC-HEART-DISEASE C1 [Baxi, Sanjiv M.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Baxi, Sanjiv M.] Univ Calif Berkeley, Sch Publ Hlth, Div Epidemiol, Berkeley, CA 94720 USA. [Lakin, Joshua R.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Lakin, Joshua R.] Harvard Univ, Sch Med, Boston, MA USA. RP Baxi, SM (reprint author), Univ Calif San Francisco, Dept Med, Div Prevent Med, 513 Parnassus Ave,Room S380, San Francisco, CA 94143 USA. EM sanjiv.baxi@ucsf.edu FU NIMH NIH HHS [T32 MH19105, T32 MH019105] NR 5 TC 1 Z9 1 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD AUG PY 2015 VL 175 IS 8 BP 1272 EP 1273 DI 10.1001/jamainternmed.2015.2100 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA CR1BL UT WOS:000361057700005 PM 26052986 ER PT J AU Chatterjee, P Venkataramani, AS Vijayan, A Wellen, JR Martin, EG AF Chatterjee, Paula Venkataramani, Atheendar S. Vijayan, Anitha Wellen, Jason R. Martin, Erika G. TI The Effect of State Policies on Organ Donation and Transplantation in the United States SO JAMA INTERNAL MEDICINE LA English DT Article ID LIVING KIDNEY DONATION; DONOR ORGANS; INCREASE; LEGISLATION; REGISTRY; IMPACT AB IMPORTANCE Shortages in transplantable solid organs remain a critical public health challenge in the United States. During the past 2 decades, all states have implemented policies to increase organ supply, although their effectiveness is unknown. OBJECTIVE To determine the effects on organ donation and transplantation rates of state policies to provide incentives for volunteer donation. DESIGN, SETTING, AND PARTICIPANTS Using a quasi-experimental design and difference-in-differences regression analyses, we estimated the effect of policies in all 50 states and the District of Columbia on organ donors per capita and the number of transplantations from January 1, 1988, to December 31, 2010. Analyses were also stratified by type of donor (living vs deceased). Data were derived from the United Network for Organ Sharing. All data collection occurred between July 7 and September 27, 2013. EXPOSURES Policies of interest were the presence of first-person consent laws, donor registries, dedicated revenue streams for donor recruitment activities, population education programs, paid leave for donation, and tax incentives. Information on states' passage of various policies was obtained from primary legislative and legal sources. MAIN OUTCOMES AND MEASURES The number of organ donors and transplantations per state, per year, during the study period. RESULTS From 1988 to 2010, the number of states passing at least 1 donation-related policy increased from 7 (14%) to 50 (100%). First-person consent laws, donor registries, public education, paid leave, and tax incentives had no robust, significant association with either donation rates or number of transplants. The establishment of revenue policies, in which individuals contribute to a protected state fund for donation promotion activities, was associated with a 5.3% increase in the absolute number of transplants (95% CI, 0.57%-10.1%; P =.03). These associations were driven by a 4.9% increase in organ donations (95% CI, 0.97%-8.7%; P =.01) and an 8.0% increase in transplants (95% CI, 3.1%-12.9%; P =.001) from deceased donors as opposed to changes among living donors or transplants from living donors. CONCLUSIONS AND RELEVANCE Nearly all state-level policies to encourage organ donation have had no observable effect on the rate of organ donation and transplantation in the United States. The one exception was the establishment of revenue policies to promote organ donation, which may have led to small increases in organ donations and transplantations from deceased donors. New policy designs are needed to increase donation rates and curtail the widening gap between organ supply and demand. C1 [Chatterjee, Paula] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Chatterjee, Paula; Venkataramani, Atheendar S.] Harvard Univ, Sch Med, Boston, MA USA. [Venkataramani, Atheendar S.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Venkataramani, Atheendar S.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Vijayan, Anitha] Washington Univ, Sch Med, Dept Med, Div Renal Dis, St Louis, MO 63110 USA. [Wellen, Jason R.] Washington Univ, Sch Med, Dept Surg, Sect Transplantat, St Louis, MO 63110 USA. [Martin, Erika G.] SUNY Albany, Nelson A Rockefeller Inst Govt, Albany, NY 12222 USA. [Martin, Erika G.] SUNY Albany, Rockefeller Coll Publ Affairs & Policy, Dept Publ Adm & Policy, Albany, NY 12222 USA. RP Martin, EG (reprint author), SUNY Albany, Rockefeller Coll Publ Affairs & Policy, Dept Publ Adm & Policy, 1400 Washington Ave,Milne 300E, Albany, NY 12222 USA. EM emartin@albany.edu NR 31 TC 10 Z9 10 U1 1 U2 11 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 2015 VL 175 IS 8 BP 1323 EP 1329 DI 10.1001/jamainternmed.2015.2194 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CR1BL UT WOS:000361057700015 PM 26030386 ER PT J AU Friedberg, MW Rosenthal, MB Werner, RM Volpp, KG Schneider, EC AF Friedberg, Mark W. Rosenthal, Meredith B. Werner, Rachel M. Volpp, Kevin G. Schneider, Eric C. TI Effects of a Medical Home and Shared Savings Intervention on Quality and Utilization of Care SO JAMA INTERNAL MEDICINE LA English DT Article ID LONGITUDINAL DATA-ANALYSIS; PATIENT SATISFACTION; EFFICIENCY; PROVIDERS; FEATURES; BURNOUT; COSTS AB IMPORTANCE Published evaluations of medical home interventions have found limited effects on quality and utilization of care. OBJECTIVE To measure associations between participation in the Northeastern Pennsylvania Chronic Care Initiative and changes in quality and utilization of care. DESIGN, SETTING, AND PARTICIPANTS The northeast region of the Pennsylvania Chronic Care Initiative began in October 2009, included 2 commercial health plans and 27 volunteering small primary care practice sites, and was designed to run for 36 months. Both participating health plans provided medical claims and enrollment data spanning October 1, 2007, to September 30, 2012 (2 years prior to and 3 years after the pilot inception date). We analyzed medical claims for 17 363 patients attributed to 27 pilot and 29 comparison practices, using difference-in-difference methods to estimate changes in quality and utilization of care associated with pilot participation. EXPOSURES The intervention included learning collaboratives, disease registries, practice coaching, payments to support care manager salaries and practice transformation, and shared savings incentives (bonuses of up to 50% of any savings generated, contingent on meeting quality targets). As a condition of participation, pilot practices were required to attain recognition by the National Committee for Quality Assurance as medical homes. MAIN OUTCOMES AND MEASURES Performance on 6 quality measures for diabetes and preventive care; utilization of hospital, emergency department, and ambulatory care. RESULTS All pilot practices received recognition as medical homes during the intervention. By intervention year 3, relative to comparison practices, pilot practices had statistically significantly better performance on 4 process measures of diabetes care and breast cancer screening; lower rates of all-cause hospitalization (8.5 vs 10.2 per 1000 patients per month; difference, -1.7 [95% CI, -3.2 to -0.03]), lower rates of all-cause emergency department visits (29.5 vs 34.2 per 1000 patients per month; difference, -4.7 [95% CI, -8.7 to -0.9]), lower rates of ambulatory care-sensitive emergency department visits (16.2 vs 19.4 per 1000 patients per month; difference, -3.2 [95% CI, -5.7 to -0.9]), lower rates of ambulatory visits to specialists (104.9 vs 122.2 per 1000 patients per month; difference, -17.3 [95% CI, -26.6 to -8.0]); and higher rates of ambulatory primary care visits (349.0 vs 271.5 per 1000 patients per month; difference, 77.5 [95% CI, 37.3 to 120.5]). CONCLUSIONS AND RELEVANCE During a 3-year period, this medical home intervention, which included shared savings for participating practices, was associated with relative improvements in quality, increased primary care utilization, and lower use of emergency department, hospital, and specialty care. With further experimentation and evaluation, such interventions may continue to become more effective. C1 [Friedberg, Mark W.; Schneider, Eric C.] RAND Corp, Boston, MA USA. [Friedberg, Mark W.; Schneider, Eric C.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Friedberg, Mark W.; Schneider, Eric C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Rosenthal, Meredith B.; Schneider, Eric C.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Werner, Rachel M.; Volpp, Kevin G.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Werner, Rachel M.; Volpp, Kevin G.] Univ Penn, Perelman Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Wharton Business Sch, Dept Hlth Care Management, Philadelphia, PA USA. [Volpp, Kevin G.] Penn Med Ctr Hlth Care Innovat, Philadelphia, PA USA. RP Friedberg, MW (reprint author), 20 Pk Plaza,Ste 920, Boston, MA 02116 USA. EM mfriedbe@rand.org OI Schneider, Eric/0000-0002-1132-5084 FU Commonwealth Fund FX This study was sponsored by the Commonwealth Fund. NR 26 TC 21 Z9 21 U1 1 U2 8 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 2015 VL 175 IS 8 BP 1362 EP 1368 DI 10.1001/jamainternmed.2015.2047 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CR1BL UT WOS:000361057700023 PM 26030123 ER PT J AU Tiet, QQ Leyva, YE Moos, RH Frayne, SM Osterberg, L Smith, B AF Tiet, Quyen Q. Leyva, Yani E. Moos, Rudolf H. Frayne, Susan M. Osterberg, Lars Smith, Brandy TI Screen of Drug Use Diagnostic Accuracy of a New Brief Tool for Primary Care SO JAMA INTERNAL MEDICINE LA English DT Article ID NEUROPSYCHIATRIC INTERVIEW MINI; RANDOMIZED CLINICAL-TRIAL; BRIEF INTERVENTION; USE DISORDERS; ALCOHOL; SETTINGS; INSTRUMENTS; RELIABILITY; VALIDATION; VALIDITY AB IMPORTANCE Illicit drug use is prevalent, and primary care provides an ideal setting in which to screen for drug use disorders (DUDs) and negative consequences of drug use (NCDU). Comprehensive reviews have concluded that existing drug use screening instruments are not appropriate for routine use in primary care. OBJECTIVE To develop and validate a screening instrument for drug use. DESIGN, SETTING, AND PARTICIPANTS We revised items drawn from existing screening instruments and conducted signal detection analyses to develop the new instrument. We approached 3173 patients at 2 primary care clinics in a US Department of Veterans Affairs health care system from February 1, 2012, through April 30, 2014. A total of 1300 (41.0%) patients consented to the study, of whom 1283 adults were eligible (mean [SD] age, 62.2 [12.6] years). In the last 12 months, 241 (18.8%) participants reported using illicit drugs or prescription medication for a nonmedical purpose, and 189 (14.7%) reported 1 or more NCDU. A total of 133 (10.4%) patients met DSM-IV criteria for a DUD. The sample was randomly divided first to develop the measure and then to validate it. MAIN OUTCOMES AND MEASURES The Mini-International Diagnostic Interview was used as the criterion for DUDs, and the Inventory of Drug Use Consequences was used as the criterion for NCDU. RESULTS The screening instrument has 2 questions. The first is, "How many days in the past 12 months have you used drugs other than alcohol?" Patients meet that criterion with a response of 7 or more days. The second question asks, "How many days in the past 12 months have you used drugs more than you meant to?" A response of 2 or more days meets that criterion. The screening instrument was 100% sensitive and 93.73% specific for DUDs (643 patients); when replicated in the second half of the sample (640 patients), it was 92.31% sensitive and 92.87% specific. The screening instrument was 93.18% sensitive and 96.03% specific for NCDU (643 patients); when replicated in the second half of the sample (640 patients), it was 83.17% sensitive and 96.85% specific. CONCLUSIONS AND RELEVANCE The 2-item screen of drug use has excellent statistical properties and is a brief screening instrument for DUDs and problems suitable for busy US Department of Veterans Affairs primary care clinics. C1 [Tiet, Quyen Q.; Leyva, Yani E.; Moos, Rudolf H.; Frayne, Susan M.; Smith, Brandy] VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, Menlo Pk, CA 94025 USA. [Tiet, Quyen Q.; Leyva, Yani E.; Smith, Brandy] VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Disseminat & Training Div, Menlo Pk, CA 94025 USA. [Tiet, Quyen Q.; Moos, Rudolf H.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Tiet, Quyen Q.] Alliant Int Univ, Calif Sch Profess Psychol, Clin Psychol PhD Program, San Francisco, CA USA. [Leyva, Yani E.] San Francisco VA Med Ctr, Div Res, San Francisco, CA USA. [Frayne, Susan M.; Osterberg, Lars] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Osterberg, Lars] VA Palo Alto Hlth Care Syst, Gen Internal Med, Palo Alto, CA USA. RP Tiet, QQ (reprint author), VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, 795 Willow Rd, Menlo Pk, CA 94025 USA. EM quyen.tiet@va.gov FU Department of Veterans Affairs, Health Services Research and Development [IIR 10-347] FX Dr Tiet reported receiving grant IIR 10-347 from the Department of Veterans Affairs, Health Services Research and Development. NR 31 TC 5 Z9 5 U1 2 U2 3 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 2015 VL 175 IS 8 BP 1371 EP 1377 DI 10.1001/jamainternmed.2015.2438 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CR1BL UT WOS:000361057700025 PM 26075352 ER PT J AU Subak, LL King, WC Belle, SH Chen, JY Courcoulas, AP Ebel, FE Flum, DR Khandelwal, S Pender, JR Pierson, SK Pories, WJ Steffen, KJ Strain, GW Wolfe, BM Huang, AJ AF Subak, Leslee L. King, Wendy C. Belle, Steven H. Chen, Jia-Yuh Courcoulas, Anita P. Ebel, Faith E. Flum, David R. Khandelwal, Saurabh Pender, John R. Pierson, Sheila K. Pories, Walter J. Steffen, Kristine J. Strain, Gladys W. Wolfe, Bruce M. Huang, Alison J. TI Urinary Incontinence Before and After Bariatric Surgery SO JAMA INTERNAL MEDICINE LA English DT Article ID PELVIC FLOOR DISORDERS; WEIGHT-LOSS SURGERY; MIDDLE-AGED WOMEN; QUALITY-OF-LIFE; OBESE WOMEN; OLDER WOMEN; UNITED-STATES; FECAL INCONTINENCE; PHYSICAL-ACTIVITY; RISK-FACTORS AB IMPORTANCE Among women and men with severe obesity, evidence for improvement in urinary incontinence beyond the first year after bariatric surgery-induced weight loss is lacking. OBJECTIVES To examine change in urinary incontinence before and after bariatric surgery and to identify factors associated with improvement and remission among women and men in the first 3 years after bariatric surgery. DESIGN, SETTING, AND PARTICIPANTS The Longitudinal Assessment of Bariatric Surgery 2 is an observational cohort study at 10 US hospitals in 6 geographically diverse clinical centers. Participants were recruited between February 21, 2005, and February 17, 2009. Adults undergoing first-time bariatric surgical procedures as part of clinical care by participating surgeons between March 14, 2006, and April 24, 2009, were followed up for 3 years (through October 24, 2012). INTERVENTION Participants undergoing bariatric surgery completed research assessments before the procedure and annually thereafter. MAIN OUTCOMES AND MEASURES The frequency and type of urinary incontinence episodes in the past 3 months were assessed using a validated questionnaire. Prevalent urinary incontinence was defined as at least weekly urinary incontinence episodes, and remission was defined as change from prevalent urinary incontinence at baseline to less than weekly urinary incontinence episodes at follow-up. RESULTS Of 2458 participants, 1987 (80.8%) completed baseline and follow-up assessments. At baseline, the median age was 47 years (age range, 18-78 years), the median body mass index was 46 kg/m(2) (range, 34-94 kg/m(2)), and 1565 of 1987 (78.8%) were women. Urinary incontinence was more prevalent among women (49.3%; 95% CI, 46.9%-51.9%) than men (21.8%; 95% CI, 18.2%-26.1%) (P <.001). After a mean 1-year weight loss of 29.5%(95% CI, 29.0%-30.1%) in women and 27.0%(95% CI, 25.9%-28.6%) in men, year 1 urinary incontinence prevalence was significantly lower among women (18.3%; 95% CI, 16.4%-20.4%) and men (9.8%; 95% CI, 7.2%-13.4%) (P <.001 for all). The 3-year prevalence was higher than the 1-year prevalence for both sexes (24.8%; 95% CI, 21.8%-26.5% among women and 12.2%; 95% CI, 9.0%-16.4% among men) but was substantially lower than baseline (P <.001 for all). Weight loss was independently related to urinary incontinence remission (relative risk, 1.08; 95% CI, 1.06-1.10 in women and 1.07; 95% CI, 1.02-1.13 in men) per 5% weight loss, as were younger age and the absence of a severe walking limitation. CONCLUSIONS AND RELEVANCE Among women and men with severe obesity, bariatric surgery was associated with substantially reduced urinary incontinence over 3 years. Improvement in urinary incontinence may be an important benefit of bariatric surgery. C1 [Subak, Leslee L.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. [Subak, Leslee L.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Subak, Leslee L.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. [Subak, Leslee L.] San Francisco VA Med Ctr, San Francisco, CA USA. [King, Wendy C.; Belle, Steven H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Belle, Steven H.; Chen, Jia-Yuh] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Courcoulas, Anita P.; Pierson, Sheila K.] Univ Pittsburgh, Med Ctr, Dept Surg, Pittsburgh, PA USA. [Ebel, Faith E.; Strain, Gladys W.] Weill Cornell Med Coll, GI Metab & Bariatr Surg, New York, NY USA. [Flum, David R.; Khandelwal, Saurabh] Univ Washington, Dept Surg, Seattle, WA 98195 USA. [Pender, John R.; Pories, Walter J.] E Carolina Univ, Brody Sch Med, Dept Surg, Greenville, NC USA. [Steffen, Kristine J.] Univ N Dakota, Sch Med & Hlth Sci, Neuropsychiat Res Unit, Dept Neurosci, Grand Forks, ND 58201 USA. RP Subak, LL (reprint author), Univ Calif San Francisco, UCSF Womens Hlth Clin Res Ctr, Dept Obstet Gynecol & Reprod Sci, 550 16th St,Sixth Floor,Mailstop 1793, San Francisco, CA 94143 USA. EM leslee.subak@ucsf.edu OI King, Wendy/0000-0002-0740-0029 FU National Institute of Diabetes and Digestive and Kidney Diseases [U01 DK066557, U01-DK66667, UL1-RR024996, U01-DK66568, M01RR-00037, U01-DK66471, U01-DK66526, U01-DK66585, UL1-RR024153, U01-DK66555, K24 DK080775] FX The Longitudinal Assessment of Bariatric Surgery 2 represents a cooperative agreement funded by the National Institute of Diabetes and Digestive and Kidney Diseases, including the following grant numbers: grant U01 DK066557 (Data Coordinating Center), grant U01-DK66667 (Columbia University Medical Center) in collaboration with grant UL1-RR024996 (Cornell University Medical Center), grant U01-DK66568 (University of Washington) in collaboration with grant M01RR-00037 (Cornell University Medical Center), grant U01-DK66471 (Neuropsychiatric Research Institute), grant U01-DK66526 (East Carolina University), grant U01-DK66585 (University of Pittsburgh Medical Center) in collaboration with grant UL1-RR024153 (Cornell University Medical Center), and grant U01-DK66555 (Oregon Health & Science University). Dr Subak is the recipient of grant K24 DK080775 from the National Institute of Diabetes and Digestive and Kidney Diseases. NR 43 TC 12 Z9 12 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 2015 VL 175 IS 8 BP 1378 EP 1387 DI 10.1001/jamainternmed.2015.2609 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CR1BL UT WOS:000361057700027 PM 26098620 ER PT J AU Smith-Bindman, R Moghadassi, M Griffey, RT Camargo, CA Bailitz, J Beland, M Miglioretti, DL AF Smith-Bindman, Rebecca Moghadassi, Michelle Griffey, Richard T. Camargo, Carlos A., Jr. Bailitz, John Beland, Michael Miglioretti, Diana L. TI Computed Tomography Radiation Dose in Patients With Suspected Urolithiasis SO JAMA INTERNAL MEDICINE LA English DT Letter ID NEPHROLITHIASIS C1 [Smith-Bindman, Rebecca; Moghadassi, Michelle] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Smith-Bindman, Rebecca] Univ Calif San Francisco, Dept Epidemiol & Biostat, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94143 USA. [Griffey, Richard T.] Washington Univ, Sch Med, Div Emergency Med, St Louis, MO USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Bailitz, John] Cook Cty Rush Univ Med Ctr, John H Stroger Jr Hosp Cook Cty, Dept Emergency Med, Chicago, IL USA. [Beland, Michael] Rhode Isl Hosp, Dept Radiol, Providence, RI USA. [Beland, Michael] Brown Univ, Dept Radiol, Providence, RI 02912 USA. [Miglioretti, Diana L.] Univ Calif Davis, Dept Publ Hlth Sci, Div Biostat, Davis, CA 95616 USA. [Miglioretti, Diana L.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. RP Smith-Bindman, R (reprint author), Univ Calif San Francisco, Dept Radiol & Biomed Imaging, 350 Parnassus Ave,Room 307, San Francisco, CA 94143 USA. EM rebecca.smith-bindman@ucsf.edu FU AHRQ HHS [R01HS019312]; NCI NIH HHS [K24CA125036-04] NR 6 TC 5 Z9 6 U1 1 U2 3 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 2015 VL 175 IS 8 BP 1413 EP 1416 DI 10.1001/jamainternmed.2015.2697 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA CR1BL UT WOS:000361057700035 PM 26121191 ER PT J AU Sanghavi, P Jena, AB Zaslavsky, AM AF Sanghavi, Prachi Jena, Anupam B. Zaslavsky, Alan M. TI Outcomes After Out-of-Hospital Cardiac Arrest Treated by Basic vs Advanced Life Support Reply SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Sanghavi, Prachi] Harvard Univ, Program Hlth Policy, Fac Arts & Sci, Cambridge, MA 02138 USA. [Jena, Anupam B.; Zaslavsky, Alan M.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Jena, Anupam B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jena, Anupam B.] Natl Bur Econ Res, Cambridge, MA 02138 USA. RP Sanghavi, P (reprint author), Harvard Univ, Program Hlth Policy, 1737 Cambridge St,K311, Cambridge, MA 02138 USA. EM sanghav@fas.harvard.edu NR 3 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD AUG PY 2015 VL 175 IS 8 BP 1423 EP 1423 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CR1BL UT WOS:000361057700045 PM 26236978 ER PT J AU Folmer, RL Theodoroff, SM Casiana, L Shi, YB Griest, S Vachhani, J AF Folmer, Robert L. Theodoroff, Sarah M. Casiana, Linda Shi, Yongbing Griest, Susan Vachhani, Jay TI Repetitive Transcranial Magnetic Stimulation Treatment for Chronic Tinnitus A Randomized Clinical Trial SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID QUALITY-OF-LIFE; TEMPOROPARIETAL JUNCTION; AUDITORY-CORTEX; DEPRESSION; MANAGEMENT; DISTRESS; INDEX; RTMS AB IMPORTANCE Chronic tinnitus negatively affects the quality of life for millions of people. This clinical trial assesses a potential treatment for tinnitus. OBJECTIVES To determine if repetitive transcranial magnetic stimulation (rTMS) can reduce the perception or severity of tinnitus and to test the hypothesis that rTMS will result in a statistically significantly greater percentage of responders to treatment in an active rTMS group compared with a placebo rTMS group. DESIGN, SETTING, AND PARTICIPANTS A randomized, participant and clinician or observer-blinded, placebo-controlled clinical trial of rTMS involving individuals who experience chronic tinnitus. Follow-up assessments were conducted at 1, 2, 4, 13, and 26 weeks after the last treatment session. The trial was conducted between April 2011 and December 2014 at Portland Veterans Affairs Medical Center among 348 individuals with chronic tinnitus who were initially screened for participation. Of those, 92 provided informed consent and underwent more detailed assessments. Seventy individuals met criteria for inclusion and were randomized to receive active or placebo rTMS. Sixty-four participants (51 men and 13 women, with a mean [SD] age of 60.6 [8.9] years) were included in the data analyses. No participants withdrew because of adverse effects of rTMS. INTERVENTIONS Participants received 2000 pulses per session of active or placebo rTMS at a rate of 1-Hz rTMS daily on 10 consecutive workdays. MAIN OUTCOMES AND MEASURES The Tinnitus Functional Index (TFI) was the main study outcome. Our hypothesis was tested by comparing baseline and posttreatment TFIs for each participant and group. RESULTS Overall, 18 of 32 participants (56%) in the active rTMS group and 7 of 32 participants (22%) in the placebo rTMS group were responders to rTMS treatment. The difference in the percentage of responders to treatment in each group was statistically significant (chi(2)(1) = 7.94, P < .005). CONCLUSIONS AND RELEVANCE Application of 1-Hz rTMS daily for 10 consecutive workdays resulted in a statistically significantly greater percentage of responders to treatment in the active rTMS group compared with the placebo rTMS group. Improvements in tinnitus severity experienced by responders were sustained during the 26-week follow-up period. Before this procedure can be implemented clinically, larger studies should be conducted to refine treatment protocols. C1 [Folmer, Robert L.; Theodoroff, Sarah M.; Casiana, Linda; Shi, Yongbing; Griest, Susan; Vachhani, Jay] Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, Portland, OR 97239 USA. [Folmer, Robert L.; Theodoroff, Sarah M.; Griest, Susan] Oregon Hlth & Sci Univ, Dept Otolaryngol, Portland, OR 97201 USA. RP Folmer, RL (reprint author), Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM robert.folmer@va.gov NR 51 TC 12 Z9 12 U1 2 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6181 EI 2168-619X J9 JAMA OTOLARYNGOL JI JAMA Otolaryngol-Head Neck Surg. PD AUG PY 2015 VL 141 IS 8 BP 716 EP 722 DI 10.1001/jamaoto.2015.1219 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CR1AW UT WOS:000361056100008 PM 26181507 ER PT J AU Sagara, Y Mallory, MA Wong, S Aydogan, F DeSantis, S Barry, WT Golshan, M AF Sagara, Yasuaki Mallory, Melissa Anne Wong, Stephanie Aydogan, Fatih DeSantis, Stephen Barry, William T. Golshan, Mehra TI Survival Benefit of Breast Surgery for Low-Grade Ductal Carcinoma In Situ A Population-Based Cohort Study SO JAMA SURGERY LA English DT Article ID MULTIPLE IMPUTATION; PROPENSITY SCORE; PROSTATE-CANCER; DIAGNOSIS; BIOPSY; OVERDIAGNOSIS; RECURRENCE; MANAGEMENT; OUTCOMES; DISEASE AB IMPORTANCE While the prevalence of ductal carcinoma in situ (DCIS) of the breast has increased substantially following the introduction of breast-screening methods, the clinical significance of early detection and treatment for DCIS remains unclear. OBJECTIVE To investigate the survival benefit of breast surgery for low-grade DCIS. DESIGN, SETTING, AND PARTICIPANTS A retrospective longitudinal cohort study using the Surveillance, Epidemiology, and End Results (SEER) database from October 9, 2014, to January 15, 2015, at the Dana-Farber/Brigham Women's Cancer Center. Between 1988 and 2011, 57 222 eligible cases of DCIS with known nuclear grade and surgery status were identified. EXPOSURES Patients were divided into surgery and nonsurgery groups. MAIN OUTCOMES AND MEASURES Propensity score weighting was used to balance patient backgrounds between groups. A log-rank test and multivariable Cox proportional hazards model was used to assess factors related to overall and breast cancer-specific survival. RESULTS Of 57 222 cases of DCIS identified in this study, 1169 cases (2.0%) were managed without surgery and 56 053 cases (98.0%) were managed with surgery. With a median follow-up of 72 months from diagnosis, there were 576 breast cancer-specific deaths (1.0%). The weighted 10-year breast cancer-specific survival was 93.4% for the nonsurgery group and 98.5% for the surgery group (log-rank test, P < .001). The degree of survival benefit among those managed surgically differed according to nuclear grade (P = .003). For low-grade DCIS, the weighted 10-year breast cancer-specific survival of the nonsurgery group was 98.8% and that of the surgery group was 98.6%(P = .95). Multivariable analysis showed there was no significant difference in the weighted hazard ratios of breast cancer-specific survival between the surgery and nonsurgery groups for low-grade DCIS. The weighted hazard ratios of intermediate-and high-grade DCIS were significantly different (low grade: hazard ratio, 0.85; 95% CI, 0.21-3.52; intermediate grade: hazard ratio, 0.23; 95% CI, 0.14-0.42; and high grade: hazard ratio, 0.15; 95% CI, 0.11-0.23) and similar results were seen for overall survival. CONCLUSIONS AND RELEVANCE The survival benefit of performing breast surgery for low-grade DCIS was lower than that for intermediate-or high-grade DCIS. A prospective clinical trial is warranted to investigate the feasibility of active surveillance for the management of low-grade DCIS. C1 [Sagara, Yasuaki; Mallory, Melissa Anne; Aydogan, Fatih; Golshan, Mehra] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Wong, Stephanie] McGill Univ, Dept Surg, Ctr Hlth, Montreal, PQ H3A 2T5, Canada. [Wong, Stephanie] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Aydogan, Fatih] Istanbul Univ, Cerrahpasa Med Sch, Dept Breast Surg, Istanbul, Turkey. [DeSantis, Stephen] Dana Farber Canc Inst, Dept Breast Oncol, Boston, MA 02115 USA. [Barry, William T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Sagara, Y (reprint author), Harvard Univ, Div Surg Oncol, Sch Med, Dana Farber Brigham & Womens Canc Ctr, 450 Brookline Ave,Yawkey Ste 1444, Boston, MA 02215 USA. EM ysagara@partners.org NR 34 TC 21 Z9 21 U1 0 U2 8 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 2015 VL 150 IS 8 BP 739 EP 745 DI 10.1001/jamasurg.2015.0876 PG 7 WC Surgery SC Surgery GA CR1BO UT WOS:000361058000011 PM 26039049 ER PT J AU Amri, R Berger, DL AF Amri, Ramzi Berger, David L. TI Elevation of Pretreatment Carcinoembryonic Antigen Level as a Prognostic Factor for Colon Cancer Incorporating a C Stage in the AJCC TNM Classification SO JAMA SURGERY LA English DT Editorial Material C1 [Amri, Ramzi; Berger, David L.] Massachusetts Gen Hosp, Div Gen Surg & Gastrointestinal Surg, Boston, MA 02114 USA. [Amri, Ramzi; Berger, David L.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Berger, DL (reprint author), Massachusetts Gen Hosp, Div Gen Surg & Gastrointestinal Surg, 15 Parkman St, Boston, MA 02114 USA. EM dberger@mgh.harvard.edu OI Amri, Ramzi/0000-0001-7416-6650 NR 5 TC 1 Z9 1 U1 0 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 2015 VL 150 IS 8 BP 755 EP 756 DI 10.1001/jamasurg.2015.0901 PG 3 WC Surgery SC Surgery GA CR1BO UT WOS:000361058000014 PM 26083189 ER PT J AU Hempel, S Maggard-Gibbons, M Nguyen, DK Dawes, AJ Miake-Lye, I Beroes, JM Booth, MJ Miles, JNV Shanman, R Shekelle, PG AF Hempel, Susanne Maggard-Gibbons, Melinda Nguyen, David K. Dawes, Aaron J. Miake-Lye, Isomi Beroes, Jessica M. Booth, Marika J. Miles, Jeremy N. V. Shanman, Roberta Shekelle, Paul G. TI Wrong-Site Surgery, Retained Surgical Items, and Surgical Fires A Systematic Review of Surgical Never Events SO JAMA SURGERY LA English DT Review ID WRONG INTRAOCULAR-LENS; PREVENTING WRONG SITE; OPERATING-ROOM FIRES; WRONG-LEVEL SURGERY; FOREIGN-BODY LEFT; SPINE SURGERY; RISK-FACTORS; UNIVERSAL PROTOCOL; TOOTH EXTRACTION; MEDICAL-CENTER AB IMPORTANCE Serious, preventable surgical events, termed never events, continue to occur despite considerable patient safety efforts. OBJECTIVE To examine the incidence and root causes of and interventions to prevent wrong-site surgery, retained surgical items, and surgical fires in the era after the implementation of the Universal Protocol in 2004. DATA SOURCES We searched 9 electronic databases for entries from 2004 through June 30, 2014, screened references, and consulted experts. STUDY SELECTION Two independent reviewers identified relevant publications in June 2014. DATA EXTRACTION AND SYNTHESIS One reviewer used a standardized form to extract data and a second reviewer checked the data. Strength of evidence was established by the review team. Data extraction was completed in January 2015. MAIN OUTCOMES AND MEASURES Incidence of wrong-site surgery, retained surgical items, and surgical fires. RESULTS We found 138 empirical studies that met our inclusion criteria. Incidence estimates for wrong-site surgery in US settings varied by data source and procedure (median estimate, 0.09 events per 10 000 surgical procedures). The median estimate for retained surgical items was 1.32 events per 10 000 procedures, but estimates varied by item and procedure. The per-procedure surgical fire incidence is unknown. A frequently reported root cause was inadequate communication. Methodologic challenges associated with investigating changes in rare events limit the conclusions of 78 intervention evaluations. Limited evidence supported the Universal Protocol (5 studies), education (4 studies), and team training (4 studies) interventions to prevent wrong-site surgery. Limited evidence exists to prevent retained surgical items by using data-matrix-coded sponge-counting systems (5 pertinent studies). Evidence for preventing surgical fires was insufficient, and intervention effects were not estimable. CONCLUSIONS AND RELEVANCE Current estimates for wrong-site surgery and retained surgical items are 1 event per 100 000 and 1 event per 10 000 procedures, respectively, but the precision is uncertain, and the per-procedure prevalence of surgical fires is not known. Root-cause analyses suggest the need for improved communication. Despite promising approaches and global Universal Protocol evaluations, empirical evidence for interventions is limited. C1 [Hempel, Susanne; Booth, Marika J.; Shanman, Roberta] RAND Corp, Southern Calif Evidence Based Practice Ctr, Santa Monica, CA 90401 USA. [Maggard-Gibbons, Melinda; Dawes, Aaron J.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. [Maggard-Gibbons, Melinda; Nguyen, David K.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Dawes, Aaron J.] Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, Los Angeles, CA USA. [Miake-Lye, Isomi; Beroes, Jessica M.; Shekelle, Paul G.] West Los Angeles Vet Affairs Med Ctr, Evidence Based Synth Program ESP Ctr, Los Angeles, CA USA. [Miles, Jeremy N. V.] RAND Corp, RAND Hlth, Santa Monica, CA 90401 USA. RP Hempel, S (reprint author), RAND Corp, Southern Calif Evidence Based Practice Ctr, 1776 Main St, Santa Monica, CA 90401 USA. EM susanne_hempel@rand.org OI Dawes, Aaron/0000-0003-4574-6765 FU Department of Veterans Affairs (VA) FX The study is based on a systematic review conducted by the Evidence-Based Synthesis Program (ESP) funded by the Department of Veterans Affairs (VA). NR 83 TC 8 Z9 8 U1 0 U2 5 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 2015 VL 150 IS 8 BP 796 EP 805 DI 10.1001/jamasurg.2015.0301 PG 10 WC Surgery SC Surgery GA CR1BO UT WOS:000361058000023 PM 26061125 ER PT J AU Weiss, A Anderson, JE Chang, DC AF Weiss, Anna Anderson, Jamie E. Chang, David C. TI Comparing the National Surgical Quality Improvement Program With the Nationwide Inpatient Sample Database SO JAMA SURGERY LA English DT Letter C1 [Weiss, Anna] Univ Calif San Diego, Dept Surg, San Diego, CA 92103 USA. [Anderson, Jamie E.] Univ Calif Davis, Dept Surg, Sacramento, CA 95817 USA. [Chang, David C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Weiss, A (reprint author), Univ Calif San Diego, Dept Surg, 200 W Arbor Dr,8402, San Diego, CA 92103 USA. EM a3weiss@ucsd.edu NR 4 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD AUG PY 2015 VL 150 IS 8 BP 815 EP 816 DI 10.1001/jamasurg.2015.0962 PG 2 WC Surgery SC Surgery GA CR1BO UT WOS:000361058000028 PM 26061977 ER PT J AU Trinh, NH Hails, K Flaherty, K Chang, T Fava, M Yeung, A AF Nhi-Ha Trinh Hails, Katherine Flaherty, Katherine Chang, Trina Fava, Maurizio Yeung, Albert TI Lessons Learned: Implementation of a Culturally Focused Psychiatric Consultation Service for Latino Americans and Asian Americans SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Disparities; mental health; collaborative care; culturally appropriate care ID PRIMARY-CARE; MENTAL-HEALTH; MINORITY POPULATIONS; DEPRESSIVE SYMPTOMS; UNITED-STATES AB Novel interventions have been developed to bridge disparities in accessing mental health care for minority populations. However, challenges arise when trying to implement and study novel interventions in real-world community settings. Our objective is to describe the challenges implementing the Culturally Focused Psychiatric (CFP) Consultation Program for depressed Latino and Asian Americans in four urban primary care practices. Issues discussed at regular on-site meetings were used to inform improvements in the program's implementation, and interviews were conducted with intervention and practice staff at the end of the program to address additional avenues for improvement. Despite thoughtful planning, multiple challenges arose, highlighting the need for extended time piloting the intervention, additional staffing of the intervention, and maintaining flexibility when working with busy primary care sites to implement mental health interventions. The CFP program highlights the challenges of implementing mental health interventions for minority populations in primary care. C1 [Nhi-Ha Trinh; Hails, Katherine; Chang, Trina; Fava, Maurizio; Yeung, Albert] Massachusetts Gen Hosp, Depress Clin & Res Program, Dept Psychiat, Boston, MA 02114 USA. [Hails, Katherine] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. [Flaherty, Katherine] ABT Associates Inc, Cambridge, MA 02138 USA. RP Trinh, NH (reprint author), MGH Depress & Clin Res Program, One Bowdoin Sq,Sixth Floor, Boston, MA 02114 USA. EM ntrinh@partners.org NR 17 TC 1 Z9 1 U1 1 U2 2 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 2015 VL 26 IS 3 BP 792 EP 801 DI 10.1353/hpu.2015.0096 PG 10 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA CQ9EP UT WOS:000360915400018 PM 26320914 ER PT J AU Stainback, RF Estep, JD Agler, DA Birks, EJ Bremer, M Hung, J Kirkpatrick, JN Rogers, JG Shah, NR AF Stainback, Raymond F. Estep, Jerry D. Agler, Deborah A. Birks, Emma J. Bremer, Merri Hung, Judy Kirkpatrick, James N. Rogers, Joseph G. Shah, Nishant R. TI Echocardiography in the Management of Patients with Left Ventricular Assist Devices: Recommendations from the American Society of Echocardiography SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Editorial Material DE Echocardiography; mechanical circulatory support; left ventricular assist devices; comprehensive examination ID MECHANICAL CIRCULATORY SUPPORT; ADVANCED HEART-FAILURE; PATENT FORAMEN OVALE; INTERMACS ANNUAL-REPORT; TASK-FORCE GUIDELINES; CONTINUOUS-FLOW LVAD; AORTIC-INSUFFICIENCY; CARDIOVASCULAR-ANESTHESIOLOGISTS; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; CONTRAST ECHOCARDIOGRAPHY C1 [Stainback, Raymond F.] Texas Heart Inst, Houston, TX 77025 USA. [Estep, Jerry D.] Houston Methodist, Houston, TX USA. [Agler, Deborah A.] Cleveland Clin, Cleveland, OH 44106 USA. [Birks, Emma J.] Univ Louisville, Sch Med, Louisville, KY 40292 USA. [Bremer, Merri] Mayo Clin, Rochester, MN USA. [Hung, Judy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kirkpatrick, James N.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Rogers, Joseph G.] Duke Univ Hosp, Durham, NC USA. [Shah, Nishant R.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Stainback, RF (reprint author), Amer Soc Echocardiog, 2100 Gateway Ctr Blvd,Suite 310, Morrisville, NC 27560 USA. EM ase@asecho.org OI Stainback, Raymond/0000-0002-2089-6508 NR 95 TC 11 Z9 11 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD AUG PY 2015 VL 28 IS 8 BP 853 EP 909 DI 10.1016/j.echo.2015.05.008 PG 57 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CQ9LR UT WOS:000360936800001 PM 26239899 ER PT J AU Olsson, RF Logan, BR Chaudhury, S Zhu, X Akpek, G Bolwell, BJ Bredeson, CN Dvorak, CC Gupta, V Ho, VT Lazarus, HM Marks, DI Ringden, OTH Pasquini, MC Schriber, JR Cooke, KR AF Olsson, R. F. Logan, B. R. Chaudhury, S. Zhu, X. Akpek, G. Bolwell, B. J. Bredeson, C. N. Dvorak, C. C. Gupta, V. Ho, V. T. Lazarus, H. M. Marks, D. I. Ringden, O. T. H. Pasquini, M. C. Schriber, J. R. Cooke, K. R. TI Primary graft failure after myeloablative allogeneic hematopoietic cell transplantation for hematologic malignancies SO LEUKEMIA LA English DT Article ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; BLOOD STEM-CELL; MAJOR-HISTOCOMPATIBILITY-COMPLEX; ACUTE MYELOGENOUS LEUKEMIA; MATCHED UNRELATED DONORS; SEVERE APLASTIC-ANEMIA; RISK-FACTORS; T-CELLS; CLASS-I AB Clinical outcomes after primary graft failure (PGF) remain poor. Here we present a large retrospective analysis (n = 23 272) which investigates means to prevent PGF and early detection of patients at high risk. In patients with hematologic malignancies, who underwent their first myeloablative allogeneic hematopoietic cell transplantation, PGF was reported in 1278 (5.5%), and there was a marked difference in PGFs using peripheral blood stem cell compared with bone marrow grafts (2.5 vs 7.3%; P<0.001). A fourfold increase of PGF was observed in myeloproliferative disorders compared with acute leukemia (P<0.001). Other risk factors for PGF included recipient age <30, HLA mismatch, male recipients of female donor grafts, ABO incompatibility, busulfan/cyclophosphamide conditioning and cryopreservation. In bone marrow transplants, total nucleated cell doses <= 2.4 x 10(8) per kg were associated with PGF (odds ratio 1.39; P<0.001). The use of tacrolimus-based immunosuppression and granulocyte colony-stimulating factor were associated with decreased PGF risk. These data, allow clinicians to do more informed choices with respect to graft source, donor selection, conditioning and immunosuppressive regimens to reduce the risk of PGF. Moreover, a novel risk score determined on day 21 post transplant may provide the rationale for an early request for additional hematopoietic stem cells. C1 [Olsson, R. F.; Ringden, O. T. H.] Karolinska Inst, Div Therapeut Immunol, Dept Lab Med, S-14186 Stockholm, Sweden. [Olsson, R. F.] Uppsala Univ, Ctr Clin Res Sormland, Uppsala, Sweden. [Logan, B. R.; Zhu, X.; Pasquini, M. C.] Med Coll Wisconsin, Dept Med, CIBMTR, Milwaukee, WI 53226 USA. [Logan, B. R.] Med Coll Wisconsin, Inst Hlth & Soc, Div Biostat, Milwaukee, WI 53226 USA. [Chaudhury, S.] Ann & Robert H Lurie Childrens Hosp Chicago, Dept Pediat, Div Pediat Hematol Oncol & Stem Cell Transplant, Chicago, IL USA. [Akpek, G.] Banner MD Anderson Canc Ctr, Sect Hematol Oncol, Gilbert, AZ USA. [Bolwell, B. J.] Cleveland Clin, Dept Hematol & Oncol, Cleveland, OH 44106 USA. [Bredeson, C. N.] Ottawa Hosp, Blood & Marrow Transplant Program, Ottawa, ON, Canada. [Bredeson, C. N.] Ottawa Hosp, Res Inst, Ottawa, ON, Canada. [Dvorak, C. C.] Univ Calif San Francisco, Med Ctr, Dept Pediat, San Francisco, CA USA. [Gupta, V.] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada. [Ho, V. T.] Dana Farber Canc Inst, Ctr Hematol Oncol, Boston, MA 02115 USA. [Lazarus, H. M.] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Cleveland, OH USA. [Marks, D. I.] Univ Hosp Bristol NHS Trust, Pediat Bone Marrow Transplant, Bristol, Avon, England. [Schriber, J. R.] Virginia G Piper Canc Ctr, Canc Transplant Inst, Scottsdale, AZ USA. [Schriber, J. R.] Arizona Oncol, Scottsdale, AZ USA. [Cooke, K. R.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Pediat Blood & Marrow Transplantat Program, Baltimore, MD USA. [Ringden, O. T. H.] Ctr Allogene Stem Cell Transplantat, Stockholm, Sweden. RP Olsson, RF (reprint author), Karolinska Inst, Div Therapeut Immunol, Dept Lab Med, S-14186 Stockholm, Sweden. EM richard.olsson@ki.se FU Swedish Society for Medical Research (SSMF); Swedish Medical Society; Centre for Clinical Research Sormland; David and Astrid Hagelen's Foundation; Karolinska Institutet; National Cancer Institute (NCI) [U24-CA076518]; National Heart, Lung and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases (NIAID); NHLBI [5U10HL069294]; NCI; Health Resources and Services Administration (HRSA/DHHS) [HHSH250201200016C]; Office of Naval Research [N00014-12-1-0142, N00014-13-1-0039]; Actinium Pharmaceuticals; Allos Therapeutics, Inc.; Amgen, Inc.; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; Leukemia & Lymphoma Society; Medac GmbH; Medical College of Wisconsin; Merck Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; Remedy Informatics; Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; TerumoBCT; Teva Neuroscience, Inc.; THERAKOS, Inc.; University of Minnesota; University of Utah; Wellpoint, Inc. FX RFO thanks the Swedish Society for Medical Research (SSMF), the Swedish Medical Society, the Centre for Clinical Research Sormland, the David and Astrid Hagelen's Foundation and the Karolinska Institutet for their financial support. The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-12-1-0142 and N00014-13-1-0039 from the Office of Naval Research; and grants from Actinium Pharmaceuticals; Allos Therapeutics, Inc.; Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; Remedy Informatics; Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; TerumoBCT; Teva Neuroscience, Inc.; THERAKOS, Inc.; University of Minnesota; University of Utah; and Wellpoint, Inc. NR 59 TC 10 Z9 11 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD AUG PY 2015 VL 29 IS 8 BP 1754 EP 1762 DI 10.1038/leu.2015.75 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA CQ9LU UT WOS:000360937200015 PM 25772027 ER PT J AU Queneherve, L Neunlist, M des Varannes, SB Tearney, G Coron, E AF Queneherve, Lucille Neunlist, Michel des Varannes, Stanislas Bruley Tearney, Guillermo Coron, Emmanuel TI Novel endoscopic techniques to image the upper gastrointestinal tract SO M S-MEDECINE SCIENCES LA French DT Review ID CONFOCAL LASER ENDOMICROSCOPY; TETHERED CAPSULE ENDOMICROSCOPY; OPTICAL COHERENCE MICROSCOPY; INFLAMMATORY-BOWEL-DISEASE; BARRETTS-ESOPHAGUS; CROHNS-DISEASE; ULCERATIVE-COLITIS; CONTROLLED-TRIAL; MULTICENTER; NEOPLASIA AB Novel endoscopic techniques for the analysis of the digestive wall have recently been developed to allow investigating digestive diseases beyond standard "white-light" macroscopic imaging of the mucosal surface. Among innovative techniques under clinical evaluation, confocal endomicroscopy and optical frequency domain imaging (OFDI) are the most promising. Indeed, these techniques allow performing in vivo microscopy with different levels in terms of depths and magnification, as well as functional assessment of structures. Some of these techniques, such as capsule-based OFDI, are also less invasive than traditional endoscopy and might help screening large groups of patients for specific disorders, for instance oesophageal precancerous diseases. In this review, we will focus on the results obtained with these techniques in precancerous, inflammatory and neuromuscular disorders. C1 [Queneherve, Lucille; des Varannes, Stanislas Bruley; Coron, Emmanuel] Hop Hotel Dieu, Inst Malad Appareil Digestif, CHU Nantes, F-44093 Nantes, France. [Queneherve, Lucille; Neunlist, Michel; des Varannes, Stanislas Bruley; Coron, Emmanuel] Inserm U913, F-44093 Nantes, France. [Tearney, Guillermo] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Tearney, Guillermo] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Coron, E (reprint author), Hop Hotel Dieu, Inst Malad Appareil Digestif, CHU Nantes, 1 Pl Alexis Ricordeau, F-44093 Nantes, France. EM lucille.queneherve@gmail.com; emmanuel.coron@gmail.com RI Coron, Emmanuel/K-2415-2015 NR 22 TC 0 Z9 0 U1 1 U2 2 PU EDP SCIENCES S A PI LES ULIS CEDEX A PA 17, AVE DU HOGGAR, PA COURTABOEUF, BP 112, F-91944 LES ULIS CEDEX A, FRANCE SN 0767-0974 J9 M S-MED SCI JI M S-Med. Sci. PD AUG-SEP PY 2015 VL 31 IS 8-9 BP 777 EP 783 DI 10.1051/medsci/20153108017 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CR0VQ UT WOS:000361041900017 PM 26340838 ER PT J AU Chabner, BA AF Chabner, Bruce A. TI Breakthrough Drugs and Turtle Soup SO ONCOLOGIST LA English DT Editorial Material C1 [Chabner, Bruce A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Chabner, BA (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM bchabner@partners.org NR 5 TC 1 Z9 1 U1 0 U2 1 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 2015 VL 20 IS 8 BP 845 EP 846 DI 10.1634/theoncologist.2015-0247 PG 2 WC Oncology SC Oncology GA CQ9YR UT WOS:000360973500003 PM 26185198 ER PT J AU Gainor, JF Chabner, BA AF Gainor, Justin F. Chabner, Bruce A. TI Ponatinib: Accelerated Disapproval SO ONCOLOGIST LA English DT Editorial Material ID CHROMOSOME-POSITIVE LEUKEMIAS C1 [Gainor, Justin F.; Chabner, Bruce A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Chabner, BA (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM bchabner@partners.org NR 7 TC 8 Z9 8 U1 0 U2 1 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 2015 VL 20 IS 8 BP 847 EP 848 DI 10.1634/theoncologist.2015-0253 PG 2 WC Oncology SC Oncology GA CQ9YR UT WOS:000360973500004 PM 26173838 ER PT J AU Morgans, AK Schapira, L AF Morgans, Alicia K. Schapira, Lidia TI Confronting Therapeutic Failure: A Conversation Guide SO ONCOLOGIST LA English DT Article DE Communication; Therapeutic failure; Bad news; Coping; Clinician self-awareness ID EARLY PALLIATIVE CARE; PHASE ONCOLOGY TRIALS; CANCER-PATIENTS; DECISION-MAKING; BAD-NEWS; LIFE; PATIENT; DEATH; END; COMMUNICATION AB We reflect on the impact of bad news on both clinician and patient in the setting of cancer treatment failure. We review the classic six-step SPIKES (setting, perception, invitation for information, knowledge, empathy, summarize and strategize) protocol for giving bad news that has been widely adopted since it was first published in this journal in 2005. The goal of such a conversation guide is to describe both the process and the tasks that constitute vital steps for clinicians and to comment on the emotional impact of the conversation on the clinician. Confronting therapeutic failure is the hardest task for oncologists. We offer practical tips derived from a thorough review of the evidence and our clinical experience. C1 [Morgans, Alicia K.] Vanderbilt Univ, Med Ctr, Nashville, TN 37232 USA. [Schapira, Lidia] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Morgans, AK (reprint author), Vanderbilt Univ, Med Ctr, 2220 Pierce Ave,777 Preston Res Bldg, Nashville, TN 37232 USA. EM alicia.morgans@vanderbilt.edu FU AHRQ HHS [K12 HS022990] NR 41 TC 3 Z9 3 U1 4 U2 4 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 2015 VL 20 IS 8 BP 946 EP 951 DI 10.1634/theoncologist.2015-0050 PG 6 WC Oncology SC Oncology GA CQ9YR UT WOS:000360973500019 PM 26099747 ER PT J AU Flaherty, KT Hamilton, BK Rosen, MA Amaravadi, RK Schuchter, LM Gallagher, M Chen, H Sehgal, C O'Dwyer, PJ AF Flaherty, Keith T. Hamilton, Betty K. Rosen, Mark A. Amaravadi, Ravi K. Schuchter, Lynn M. Gallagher, Maryann Chen, Helen Sehgal, Chandra O'Dwyer, Peter J. TI Phase I/II Trial of Imatinib and Bevacizumab in Patients With Advanced Melanoma and Other Advanced Cancers SO ONCOLOGIST LA English DT Article DE Melanoma; Bevacizumab; Imatinib; Vascular endothelial growth factor; Platelet-derived growth factor ID ENDOTHELIAL-GROWTH-FACTOR; RENAL-CELL CARCINOMA; PROGRESSION-FREE SURVIVAL; ANTI-VEGF TREATMENT; II CLINICAL-TRIALS; MALIGNANT-MELANOMA; TYROSINE KINASE; IN-VIVO; METASTATIC MELANOMA; TUMOR ANGIOGENESIS AB Background. Vascular endothelial growth factor and platelet-derived growth factor signaling in the tumor microenvironment appear to cooperate in promoting tumor angiogenesis. Patients and Methods. We conducted a phase I trial combining bevacizumab (i.v. every 2 weeks) and imatinib (oral daily). Once a recommended phase II dose combination was established, a phase II trial was initiated in patients with metastatic melanoma. A Simon 2-stage design was used with 23 patients required in the first stage and 41 patients in total should the criteria to proceed be met. We required that 50% of the patients be progression-free at 16 weeks. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and power Doppler ultrasonography were performed in patients with metastatic tumors amenable to imaging with these methods at baseline and after 4 weeks. Results. A total of 17 patients were accrued to 4 dose and combination levels. Bevacizumab 10 mg/kg every 2 weeks could be safely combined with imatinib 800 mg daily. Common toxicities included fatigue, nausea, vomiting, edema, proteinuria, and anemia, but were not commonly severe. A total of 23 patients with metastatic melanoma (48% with American Joint Commission on Cancer stage M1c; median age, 63 years) were enrolled in the first stage of phase II. The 16-week progression-free survival rate was 35%, leading to termination of phase II after the first stage. In the small subset of patients who remained on study with lesions evaluable by DCE-MRI, significant decreases in tumor vascular permeability were noted, despite early disease progression using the Response Evaluation Criteria In Solid Tumors. Conclusion. Bevacizumab and imatinib can be safely combined at the maximum doses used for each agent. We did not observe significant clinical activity with this regimen in melanoma patients. C1 [Flaherty, Keith T.; Hamilton, Betty K.; Rosen, Mark A.; Amaravadi, Ravi K.; Schuchter, Lynn M.; Gallagher, Maryann; Sehgal, Chandra; O'Dwyer, Peter J.] Univ Penn, Abramson Canc Ctr, Dev Therapeut Program, Philadelphia, PA 19104 USA. [Chen, Helen] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Flaherty, KT (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM kflaherty@partners.org FU NIH (Bethesda, MD) [K23 CA104884-02] FX This study was supported by Grant K23 CA104884-02 from the NIH (Bethesda, MD). NR 53 TC 7 Z9 7 U1 0 U2 6 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 2015 VL 20 IS 8 BP 952 EP 959 DI 10.1634/theoncologist.2015-0108 PG 8 WC Oncology SC Oncology GA CQ9YR UT WOS:000360973500020 PM 26084808 ER PT J AU Iyengar, SK Sedor, JR Freedman, BI Kao, WHL Kretzler, M Keller, BJ Abboud, HE Adler, SG Best, LG Bowden, DW Burlock, A Chen, YDI Cole, SA Comeau, ME Curtis, JM Divers, J Drechsler, C Duggirala, R Elston, RC Guo, XQ Huang, HT Hoffmann, MM Howard, BV Ipp, E Kimmel, PL Klag, MJ Knowler, WC Kohn, OF Leak, TS Leehey, DJ Li, M Malhotra, A Marz, W Nair, V Nelson, RG Nicholas, SB O'Brien, SJ Pahl, MV Parekh, RS Pezzolesi, MG Rasooly, RS Rotimi, CN Rotter, JI Schelling, JR Seldin, MF Shah, VO Smiles, AM Smith, MW Taylor, KD Thameem, F Thornley-Brown, DP Truitt, BJ Wanner, C Weil, EJ Winkler, CA Zager, PG Igo, RP Hanson, RL Langefeld, CD AF Iyengar, Sudha K. Sedor, John R. Freedman, Barry I. Kao, W. H. Linda Kretzler, Matthias Keller, Benjamin J. Abboud, Hanna E. Adler, Sharon G. Best, Lyle G. Bowden, Donald W. Burlock, Allison Chen, Yii-Der Ida Cole, Shelley A. Comeau, Mary E. Curtis, Jeffrey M. Divers, Jasmin Drechsler, Christiane Duggirala, Ravi Elston, Robert C. Guo, Xiuqing Huang, Huateng Hoffmann, Michael Marcus Howard, Barbara V. Ipp, Eli Kimmel, Paul L. Klag, Michael J. Knowler, William C. Kohn, Orly F. Leak, Tennille S. Leehey, David J. Li, Man Malhotra, Alka Maerz, Winfried Nair, Viji Nelson, Robert G. Nicholas, Susanne B. O'Brien, Stephen J. Pahl, Madeleine V. Parekh, Rulan S. Pezzolesi, Marcus G. Rasooly, Rebekah S. Rotimi, Charles N. Rotter, Jerome I. Schelling, Jeffrey R. Seldin, Michael F. Shah, Vallabh O. Smiles, Adam M. Smith, Michael W. Taylor, Kent D. Thameem, Farook Thornley-Brown, Denyse P. Truitt, Barbara J. Wanner, Christoph Weil, E. Jennifer Winkler, Cheryl A. Zager, Philip G. Igo, Robert P., Jr. Hanson, Robert L. Langefeld, Carl D. CA Family Investigat Nephropathy & D TI Genome-Wide Association and Trans-ethnic Meta-Analysis for Advanced Diabetic Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND) SO PLOS GENETICS LA English DT Article ID STAGE RENAL-DISEASE; GLOMERULAR-FILTRATION-RATE; AFRICAN-AMERICANS; PROTEIN; TYPE-1; LOCI; ALBUMINURIA; POPULATIONS; EXPRESSION; RECEPTOR AB Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10(-9)). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10(-8)), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD. C1 [Iyengar, Sudha K.; Elston, Robert C.; Truitt, Barbara J.; Igo, Robert P., Jr.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. [Sedor, John R.; Schelling, Jeffrey R.] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. [Sedor, John R.] Case Western Reserve Univ, Dept Physiol & Biophys, Cleveland, OH 44106 USA. [Freedman, Barry I.] Wake Forest Sch Med, Dept Internal Med, Nephrol Sect, Winston Salem, NC USA. [Kao, W. H. Linda] Johns Hopkins Univ, Dept Epidemiol & Med, Baltimore, MD USA. [Kretzler, Matthias; Keller, Benjamin J.; Leak, Tennille S.; Nair, Viji] Univ Michigan, Dept Internal Med Nephrol, Ann Arbor, MI 48109 USA. [Abboud, Hanna E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med Nephrol, San Antonio, TX USA. [Adler, Sharon G.] Harbor UCLA Med Ctr, Dept Med, Div Nephrol & Hypertens, Torrance, CA 90509 USA. [Best, Lyle G.] Missouri Breaks Ind Res, Timber Lake, SD USA. [Bowden, Donald W.] Wake Forest Sch Med, Ctr Human Gen, Dept Biochem, Winston Salem, NC USA. [Chen, Yii-Der Ida; Guo, Xiuqing; Rotter, Jerome I.; Taylor, Kent D.; Langefeld, Carl D.] Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA. [Cole, Shelley A.; Duggirala, Ravi] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Comeau, Mary E.; Divers, Jasmin] Wake Forest Sch Med, Ctr Publ Hlth Genom, Winston Salem, NC USA. [Comeau, Mary E.; Divers, Jasmin] Wake Forest Sch Med, Dept Biostat Sci, Div Publ Hlth Sci, Winston Salem, NC USA. [Curtis, Jeffrey M.; Knowler, William C.; Malhotra, Alka; Nelson, Robert G.; Weil, E. Jennifer; Hanson, Robert L.] NIDDK, NIH, Phoenix, AZ USA. [Drechsler, Christiane] Univ Hosp Wurzburg, Div Renal, Wurzburg, Germany. [Drechsler, Christiane] Univ Hosp Wurzburg, Comprehens Heart Failure Ctr, Wurzburg, Germany. [Huang, Huateng] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA. [Hoffmann, Michael Marcus] Univ Med Ctr, Dept Clin Chem, Freiburg, Germany. [Howard, Barbara V.] MedStar Hlth Res Inst, Hyattsville, MD USA. [Ipp, Eli] Harbor UCLA Med Ctr, Dept Med, Sect Diabet & Metab, Torrance, CA 90509 USA. [Kimmel, Paul L.] NIDDK, Div Kidney Urol & Hematol Dis, Bethesda, MD 20892 USA. [Klag, Michael J.] Johns Hopkins Sch Med, Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Kohn, Orly F.] Univ Chicago Med, Dept Med, Chicago, IL USA. [Leehey, David J.] Loyola Sch Med, Dept Med, Maywood, IL USA. [Li, Man] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Maerz, Winfried] Heidelberg Univ, Graz, Austria. [Maerz, Winfried] Graz Univ, Synlab Acad, Graz, Austria. [Nicholas, Susanne B.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [O'Brien, Stephen J.] Theodosius Dobzhansky Ctr Genome Bioinformat, St Petersburg, Russia. [O'Brien, Stephen J.] Nova SE Univ, Oceanog Ctr, Ft Lauderdale, FL 33314 USA. [Pahl, Madeleine V.] Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA. [Parekh, Rulan S.] Univ Hlth Network, Hosp Sick Children, Dept Paediat & Med, Toronto, ON, Canada. [Parekh, Rulan S.] Univ Toronto, Toronto, ON, Canada. [Pezzolesi, Marcus G.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med, Boston, MA 02115 USA. [Rasooly, Rebekah S.] Natl Inst Diabet & Digest Dis, NIH, Bethesda, MD USA. [Rotimi, Charles N.] Ctr Res Genom & Global Hlth, Bethesda, MD USA. [Seldin, Michael F.] Univ Calif Davis, Sch Med, Dept Biochem & Mol Med, Davis, CA USA. [Shah, Vallabh O.] Univ New Mexico, Dept Biochem & Mol Biol, Albuquerque, NM 87131 USA. [Smiles, Adam M.] Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. [Smith, Michael W.] NHGRI, Rockville, MD USA. [Thameem, Farook] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Thornley-Brown, Denyse P.] Univ Alabama Birmingham, Nephrol, Birmingham, AL USA. [Wanner, Christoph] Univ Hosp Wurzburg, Div Nephrol, Dept Med, Wurzburg, Germany. [Winkler, Cheryl A.] NCI, Ctr Canc Res, Frederick, MD 21701 USA. [Zager, Philip G.] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA. RP Iyengar, SK (reprint author), Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. EM ski@case.edu; jrs4@case.edu; bfreedma@wakehealth.edu RI Hoffmann, Michael/D-4074-2015; Hanson, Robert/O-3238-2015; OI Hoffmann, Michael/0000-0001-8459-6080; Hanson, Robert/0000-0002-4252-7068; Rasooly, Rebekah/0000-0002-6357-5528 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [U01DK57292, U01DK57329, U01DK057300, U01DK057298, U01DK057249, U01DK57295, U01DK070657, U01DK057303, U01DK57304]; NIDDK; National Heart, Lung and Blood Institute [U01HL065520, U01HL041654, U01HL041652]; National Cancer Institute, National Institutes of Health (NIH) [N01-CO-12400]; NIH, National Cancer Institute, Center for Cancer Research; National Center for Research Resources [M01-RR-000080, M01-RR-07122, M01-RR-00425, M01-RR-00827-29, HSC M01-RR-00997, M01-RR-01346] FX This study was supported by grants U01DK57292, U01DK57329, U01DK057300, U01DK057298, U01DK057249, U01DK57295, U01DK070657, U01DK057303, and U01DK57304 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and, in part, by the Intramural Research Program of the NIDDK. Support was also received from the National Heart, Lung and Blood Institute grants U01HL065520, U01HL041654, and U01HL041652. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health (NIH), under contract N01-CO-12400 and the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This work was also supported by the National Center for Research Resources for the General Clinical Research Center grants: Case Western Reserve University, M01-RR-000080; Wake Forest University, M01-RR-07122; Harbor-University of California, Los Angeles Medical Center, M01-RR-00425; College of Medicine, University of California, Irvine, M01-RR-00827-29; University of New Mexico, HSC M01-RR-00997; and Frederic C. Bartter, M01-RR-01346. Computing resources were provided, in part, by the Wake Forest School of Medicine Center for Public Health Genomics. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 53 TC 12 Z9 13 U1 5 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD AUG PY 2015 VL 11 IS 8 AR e1005352 DI 10.1371/journal.pgen.1005352 PG 19 WC Genetics & Heredity SC Genetics & Heredity GA CQ7YP UT WOS:000360823100004 PM 26305897 ER PT J AU Narayanavari, SA Lourdault, K Sritharan, M Haake, DA Matsunaga, J AF Narayanavari, Suneel A. Lourdault, Kristel Sritharan, Manjula Haake, David A. Matsunaga, James TI Role of sph2 Gene Regulation in Hemolytic and Sphingomyelinase Activities Produced by Leptospira interrogans SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID EXTRACELLULAR RELEASE; MOLECULAR-CLONING; BINDING PROTEINS; HEME OXYGENASE; SEROVAR LAI; EXPRESSION; PATHOGENESIS; DISEASE; IRON; IDENTIFICATION AB Pathogenic members of the genus Leptospira are the causative agents of leptospirosis, a neglected disease of public and veterinary health concern. Leptospirosis is a systemic disease that in its severest forms leads to renal insufficiency, hepatic dysfunction, and pulmonary failure. Many strains of Leptospira produce hemolytic and sphingomyelinase activities, and a number of candidate leptospiral hemolysins have been identified based on sequence similarity to well-characterized bacterial hemolysins. Five of the putative hemolysins are sphingomyelinase paralogs. Although recombinant forms of the sphingomyelinase Sph2 and other hemolysins lyse erythrocytes, none have been demonstrated to contribute to the hemolytic activity secreted by leptospiral cells. In this study, we examined the regulation of sph2 and its relationship to hemolytic and sphingomyelinase activities produced by several L. interrogans strains cultivated under the osmotic conditions found in the mammalian host. The sph2 gene was poorly expressed when the Fiocruz L1-130 (serovar Copenhageni), 56601 (sv. Lai), and L495 (sv. Manilae) strains were cultivated in the standard culture medium EMJH. Raising EMJH osmolarity to physiological levels with sodium chloride enhanced Sph2 production in all three strains. In addition, the Pomona subtype kennewicki strain LC82-25 produced substantially greater amounts of Sph2 during standard EMJH growth than the other strains, and sph2 expression increased further by addition of salt. When 10% rat serum was present in EMJH along with the sodium chloride supplement, Sph2 production increased further in all strains. Osmotic regulation and differences in basal Sph2 production in the Manilae L495 and Pomona strains correlated with the levels of secreted hemolysin and sphingomyelinase activities. Finally, a transposon insertion in sph2 dramatically reduced hemolytic and sphingomyelinase activities during incubation of L. interrogans at physiologic osmolarity. Complementation of the mutation with the sph2 gene partially restored production of hemolytic and sphingomyelinase activities. These results indicate that the sph2 gene product contributes to the hemolytic and sphingomyelinase activities secreted by L. interrogans and most likely dominates those functions under the culture condition tested. C1 [Narayanavari, Suneel A.; Sritharan, Manjula] Univ Hyderabad, Dept Anim Biol, Hyderabad 500134, Andhra Pradesh, India. [Lourdault, Kristel; Matsunaga, James] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. [Lourdault, Kristel; Haake, David A.; Matsunaga, James] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Haake, David A.] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA USA. [Haake, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA. RP Narayanavari, SA (reprint author), Max Delbruck Ctr Mol Med, Berlin, Germany. EM jamesm@ucla.edu FU Veterans Affairs Merit Award; United States India Educational Foundation (USIEF) [15111348]; National Institutes of Health [R01 AI 034431] FX This work was supported by a Veterans Affairs Merit Award to JM, a Fulbright-Nehru Doctoral and Professional Research Fellowship (Grantee ID: 15111348) from the United States India Educational Foundation (USIEF) to SAN, and National Institutes of Health grant R01 AI 034431 to DAH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 51 TC 3 Z9 3 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD AUG PY 2015 VL 9 IS 8 AR e0003952 DI 10.1371/journal.pntd.0003952 PG 23 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA CQ6IO UT WOS:000360708200038 PM 26274394 ER PT J AU Alloo, A Sheu, J Butrynski, JE Deangelo, DJ George, S Murphy, GF Leboeuf, NR AF Alloo, A. Sheu, J. . Butrynski, J. . E. . Deangelo, D. J. George, S. . Murphy, G. F. Leboeuf, N. R. TI Ponatinib-induced pityriasiform, folliculocentric and ichthyosiform cutaneous toxicities SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Letter ID CHROMOSOME-POSITIVE LEUKEMIAS; CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; CYTOGENETIC RESPONSES; IMATINIB-RESISTANT; DASATINIB; NILOTINIB; INHIBITOR; PHASE-2 C1 [Alloo, A.; Leboeuf, N. R.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Murphy, G. F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Alloo, A.; Butrynski, J. . E. .; George, S. .] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. [Deangelo, D. J.] Dana Farber Canc Inst, Ctr Hematol Oncol, Boston, MA 02115 USA. [Leboeuf, N. R.] Dana Farber Canc Inst, Ctr Cutaneous Oncol, Boston, MA 02115 USA. [Sheu, J. .; Butrynski, J. . E. .; Deangelo, D. J.; George, S. .; Murphy, G. F.; Leboeuf, N. R.] Harvard Univ, Sch Med, Boston, MA USA. RP Leboeuf, NR (reprint author), Brigham & Womens Hosp, Dept Dermatol, 75 Francis St, Boston, MA 02115 USA. EM nleboeuf@partners.org NR 12 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD AUG PY 2015 VL 173 IS 2 BP 574 EP 577 DI 10.1111/bjd.13692 PG 4 WC Dermatology SC Dermatology GA CQ6EB UT WOS:000360696100048 PM 25736577 ER PT J AU Gilbert, KS Kark, SM Gehrman, P Bogdanova, Y AF Gilbert, Karma Stavitsky Kark, Sarah M. Gehrman, Philip Bogdanova, Yelena TI Sleep disturbances, TBI and PTSD: Implications for treatment and recovery SO CLINICAL PSYCHOLOGY REVIEW LA English DT Article DE Sleep; PTSD; TBI; Veterans; Cognition; Interventions; Sleep physiology; Neuromodulation; Paradoxical insomnia; Actigraphy ID TRAUMATIC BRAIN-INJURY; POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; VENTROLATERAL PREOPTIC NUCLEUS; CHRONIC PRIMARY INSOMNIA; MINOR HEAD-INJURY; IMAGERY REHEARSAL THERAPY; WAKING DISCHARGE PATTERNS; RETURNING COMBAT VETERANS AB Post-Traumatic Stress Disorder (PTSD), traumatic brain injury (TBI), and sleep problems significantly affect recovery and functional status in military personnel and Veterans returning from combat. Despite recent attention, sleep is understudied in the Veteran population. Few treatments and rehabilitation protocols target sleep, although poor sleep remains at clinical levels and continues to adversely impact functioning even after the resolution of PTSD or mild TBI symptoms. Recent developments in non-pharmacologic sleep treatments have proven efficacious as stand-alone interventions and have potential to improve treatment outcomes by augmenting traditional behavioral and cognitive therapies. This review discusses the extensive scope of work in the area of sleep as it relates to TBI and PTSD, including pathophysiology and neurobiology of sleep; existing and emerging treatment options; as well as methodological issues in sleep measurements for TBI and PTSD. Understanding sleep problems and their role in the development and maintenance of PTSD and TBI symptoms may lead to improvement in overall treatment outcomes while offering a non-stigmatizing entry in mental health services and make current treatments more comprehensive by helping to address a broader spectrum of difficulties. Published by Elsevier Ltd. C1 [Gilbert, Karma Stavitsky; Kark, Sarah M.; Bogdanova, Yelena] VA Boston Healthcare Syst, Psychol Res, Boston, MA 02130 USA. [Gilbert, Karma Stavitsky; Bogdanova, Yelena] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Gehrman, Philip] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Gehrman, Philip] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Bogdanova, Y (reprint author), VA Boston Healthcare Syst, Psychol Res 151A, 150 South Huntington Ave, Boston, MA 02130 USA. EM bogdanov@bu.edu FU Rehabilitation Research and Development Service of the Department of Veterans Affairs (VA) [D6996W, I21RX001773-01]; Boston University Clinical and Translational Science Institute [UL1-RR025771]; National Institutes of Health; VA Translation Research Center for TBI and Stress Disorders (TRACTS); VA Psychology Research Service FX This work was supported by the Rehabilitation Research and Development Service of the Department of Veterans Affairs (VA) grants D6996W and I21RX001773-01 to YB, the National Institutes of Health and Boston University Clinical and Translational Science Institute grant UL1-RR025771 to YB, the VA Translation Research Center for TBI and Stress Disorders (TRACTS) [YB], and the VA Psychology Research Service [YB and KSG]. NR 282 TC 9 Z9 10 U1 12 U2 31 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0272-7358 EI 1873-7811 J9 CLIN PSYCHOL REV JI Clin. Psychol. Rev. PD AUG PY 2015 VL 40 BP 195 EP 212 DI 10.1016/j.cpr.2015.05.008 PG 18 WC Psychology, Clinical SC Psychology GA CP9ZJ UT WOS:000360254100015 PM 26164549 ER PT J AU Caroff, SN Hurford, I Bleier, HR Gorton, GE Campbell, EC AF Caroff, Stanley N. Hurford, Irene Bleier, Henry R. Gorton, Gregg E. Campbell, E. Cabrina TI Recurrent Idiopathic Catatonia: Implications beyond the Diagnostic and Statistical Manual of Mental Disorders 5th Edition SO CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE LA English DT Article DE Catatonia; Periodic catatonia; Schizophrenia; Cycloid psychosis; Antipsychotic agents; Neuroleptic malignant syndrome ID DRUGS AB We describe a case of recurrent, life threatening, catatonic stupor, without evidence of any associated medical, toxic or mental disorder. This case provides support for the inclusion of a separate category of "unspecified catatonia" in the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) to be used to classify idiopathic cases, which appears to be consistent with Kahlbaum's concept of catatonia as a distinct disease state. But beyond the limited, cross sectional, syndromal approach adopted in DSM-5, this case more importantly illustrates the prognostic and therapeutic significance of the longitudinal course of illness in differentiating cases of catatonia, which is better defined in the Wernicke-Kleist-Leonhard classification system. The importance of differentiating cases of catatonia is further supported by the efficacy of antipsychotics in treatment of this case, contrary to conventional guidelines. C1 [Caroff, Stanley N.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Caroff, SN (reprint author), Philadelphia Vet Affairs Med Ctr, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM stanley.caroff@va.gov NR 19 TC 2 Z9 2 U1 2 U2 11 PU KOREAN COLL NEUROPSYCHOPHARMACOLOGY PI SEOUL PA RN 1003 OFFICETEL 40, 63-RO YEONGDEUNGPO-GU, SEOUL, 150-731, SOUTH KOREA SN 1738-1088 EI 2093-4327 J9 CLIN PSYCHOPHARM NEU JI Clin. Psychopharmacol. Neurosci. PD AUG PY 2015 VL 13 IS 2 BP 218 EP 221 DI 10.9758/cpn.2015.13.2.218 PG 4 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA CQ4TM UT WOS:000360597500017 PM 26243853 ER PT J AU Lukasewicz, CL Mattox, EA AF Lukasewicz, Carol L. Mattox, Elizabeth Andersson TI Understanding Clinical Alarm Safety SO CRITICAL CARE NURSE LA English DT Article ID INTENSIVE-CARE-UNIT; MONITORING ALARMS; OPERATING-ROOM; FATIGUE; BEHAVIOR; EVENTS; ICU AB Patient safety organizations and health care accreditation agencies recognize the significance of clinical alarm hazards. The Association for the Advancement of Medical Instrumentation, a nonprofit organization focused on development and use of safe and effective medical equipment, identifies alarm management as a major issue for health care organizations. ECRI Institute, a nonprofit organization that researches approaches for improving patient safety and quality of care, identifies alarm hazards as the most significant of the "Top Ten Health Technology Hazards" for 2014. A new Joint Commission National Patient Safety Goal focusing on clinical alarm safety contains new requirements for accredited hospitals to be fully implemented by 2016. Through a fictional unfolding case study, this article reviews selected contributing factors to clinical alarm hazards present in inpatient, high-acuity settings. Understanding these factors improves contributions by nurses to clinical alarm safety practice. C1 [Lukasewicz, Carol L.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Mattox, Elizabeth Andersson] VA Puget Sound Hlth Care Syst, Dept Pulm & Crit Care Med, Seattle, WA USA. RP Mattox, EA (reprint author), 344 NW 103rd St, Seattle, WA 98177 USA. EM emattox@gmail.com NR 65 TC 2 Z9 2 U1 4 U2 15 PU AMER ASSOC CRITICAL CARE NURSES PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 0279-5442 EI 1940-8250 J9 CRIT CARE NURSE JI Crit. Care Nurse PD AUG PY 2015 VL 35 IS 4 BP 45 EP 57 DI 10.4037/ccn2015113 PG 13 WC Critical Care Medicine; Nursing SC General & Internal Medicine; Nursing GA CQ4KR UT WOS:000360574100008 PM 26232801 ER PT J AU Hirai, T Kobayashi, T Nishimori, S Karaplis, AC Goltzman, D Kronenberg, HM AF Hirai, Takao Kobayashi, Tatsuya Nishimori, Shigeki Karaplis, Andrew C. Goltzman, David Kronenberg, Henry M. TI Bone Is a Major Target of PTH/PTHrP Receptor Signaling in Regulation of Fetal Blood Calcium Homeostasis SO ENDOCRINOLOGY LA English DT Article ID PARATHYROID-HORMONE; MINERAL HOMEOSTASIS; SENSING RECEPTOR; GROWTH-PLATE; DIFFERENTIATION; METABOLISM; EXPRESSION; PTHRP; CHONDROCYTES; OSTEOCLAST AB The blood calcium concentration during fetal life is tightly regulated within a narrow range by highly interactive homeostatic mechanisms that include transport of calcium across the placenta and fluxes in and out of bone; the mechanisms of this regulation are poorly understood. Our findings that endochondral bone-specific PTH/PTHrP receptor (PPR) knockout (KO) mice showed significant reduction of fetal blood calcium concentration compared with that of control littermates at embryonic day 18.5 led us to focus on bone as a possibly major determinant of fetal calcium homeostasis. We found that the fetal calcium concentration of Runx2 KO mice was significantly higher than that of control littermates, suggesting that calcium flux into bone had a considerable influence on the circulating calcium concentration. Moreover, Runx2: PTH double mutant fetuses showed calcium levels similar to those of Runx2 KO mice, suggesting that part of the fetal hypocalcemia in PTH KO mice was caused by the increment of the mineralized bone mass allowed by the formation of osteoblasts. Finally, Rank:PTH double mutant mice had a blood calcium concentration even lower than that of the either Rank KO or PTH KO mice alone at embryonic day 18.5. These observations in our genetic models suggest that PTH/PTHrP receptor signaling in bones has a significant role of the regulation of fetal blood calcium concentration and that both placental transport and osteoclast activation contribute to PTH's hypercalcemic action. They also show that PTH-independent deposition of calcium in bone is the major controller of fetal blood calcium level. C1 [Hirai, Takao; Kobayashi, Tatsuya; Nishimori, Shigeki; Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Karaplis, Andrew C.] McGill Univ, Sir Mortimer B Davis Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. [Goltzman, David] McGill Univ, Ctr Hlth, Royal Victoria Hosp, Montreal, PQ H3A 1A1, Canada. RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St, Boston, MA 02114 USA. EM kronenberg.henry@mgh.harvard.edu FU National Institutes of Health [DK 56246] FX This work was supported by the National Institutes of Health Grant DK 56246. NR 27 TC 1 Z9 1 U1 0 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 2015 VL 156 IS 8 BP 2774 EP 2780 DI 10.1210/en.2014-1835 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CQ6JN UT WOS:000360710700008 PM 26052897 ER PT J AU Van Allen, EM Garraway, LA Rosenberg, JE AF Van Allen, Eliezer M. Garraway, Levi A. Rosenberg, Jonathan E. TI Re: Floris H. Groenendijk, Jeroen de Jong, Elisabeth E. Fransen van de Putte, et al. ERBB2 Mutations Characterize a Subgroup of Muscle-invasive Bladder Cancers with Excellent Response to Neoadjuvant Chemotherapy. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2015.01.014 SO EUROPEAN UROLOGY LA English DT Letter ID CISPLATIN; DNA C1 [Van Allen, Eliezer M.; Garraway, Levi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rosenberg, Jonathan E.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. RP Rosenberg, JE (reprint author), Mem Sloan Kettering Canc Ctr, Med GU Oncol Serv, 1275 York Ave, New York, NY 10065 USA. EM rosenbj1@mskcc.org NR 5 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD AUG PY 2015 VL 68 IS 2 BP E31 EP E32 DI 10.1016/j.eururo.2015.02.044 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA CQ4JR UT WOS:000360571400002 PM 25770487 ER PT J AU Meyer, F Farrell, E AF Meyer, Fremonta Farrell, Elizabeth TI Ethical Dilemmas in Palliative Care: A Case Study of Fertility Preservation in the Context of Metastatic SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Letter ID CANCER-PATIENTS C1 [Meyer, Fremonta] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Meyer, Fremonta] Harvard Univ, Sch Med, Boston, MA USA. [Meyer, Fremonta; Farrell, Elizabeth] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02215 USA. RP Meyer, F (reprint author), Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, 450 Brookline Ave,DA2016A, Boston, MA 02215 USA. EM fremonta_meyer@dfci.harvard.edu NR 4 TC 1 Z9 1 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD AUG 1 PY 2015 VL 18 IS 8 BP 661 EP 661 DI 10.1089/jpm.2015.0169 PG 1 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CQ3VQ UT WOS:000360532400004 PM 26098359 ER PT J AU Fisher, V Lee, D McGrath, J Krejci-Manwaring, J AF Fisher, Valerie Lee, Deborah McGrath, John Krejci-Manwaring, Jennifer TI Veterans Speak Up: Current Warnings on Skin Cancer Miss the Target, Suggestions for Improvement SO MILITARY MEDICINE LA English DT Article ID UNITED-STATES; PREVENTION AB Background: Skin cancer is the most common cancer in the world and its incidence is increasing. Veterans may have increased exposure to risk factors, but data are lacking in terms of their perceptions of skin cancer and the types of prevention strategies that might resonate with this population. Objective: This study examines veterans' awareness of the risk factors for skin cancer and importance of sun protection and seeks to identify effective communication and educational strategies for this at-risk population. Methods: A telephone survey was conducted of 100 veterans, who have been diagnosed with skin cancer at the Audie Murphy Veteran's Hospital in San Antonio, Texas. Results: The majority of respondents' said that their skin cancer resulted from sun exposure and that the best way to prevent skin cancer was to use sunscreen. However, when asked if they believed they were at risk for being diagnosed with skin cancer, most veterans responded that they believed they were at little risk. In response to why veterans did not heed warnings about skin cancer, many replied that they believed skin cancer would not happen to them. A statistically significant increase in usage of sunscreen and sun protectant garments occurred after being diagnosed with skin cancer and education by their physicians. Doctors talking to patients was rated the most effective communication method to inform them about the risks of skin cancer, followed by education during basic training. Limitations: Recall bias is the major limitation with a retrospective survey design. Discussion: Our results reveal poor patient awareness of the risks of skin cancer and the benefits of sun protection before their diagnosis. The veterans agreed that the physician-patient interaction is the best and most effective means of communication, which is evident by the significant increase in sun protection and sunscreen usage after their diagnosis. Our survey revealed that other effective communication strategies included education in basic training, the use of a veteran spokes model with skin cancer, and the use of images to emphasize the severity of the disease. C1 [Fisher, Valerie; Lee, Deborah; Krejci-Manwaring, Jennifer] Univ Texas Hlth Sci Ctr San Antonio, Div Dermatol & Cutaneous Surg, Canc Therapy Res Ctr, San Antonio, TX 78229 USA. [McGrath, John; Krejci-Manwaring, Jennifer] Audie L Murphy Vet Hosp, Dept Dermatol, San Antonio, TX 78229 USA. RP Fisher, V (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Dermatol & Cutaneous Surg, Canc Therapy Res Ctr, 7979 Wurzbach Rd,Mail Code 7876, San Antonio, TX 78229 USA. NR 14 TC 0 Z9 0 U1 1 U2 3 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 2015 VL 180 IS 8 BP 892 EP 897 DI 10.7205/MILMED-D-14-00318 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA CQ3TE UT WOS:000360524800016 PM 26226533 ER PT J AU Zhang, Y Wu, IW Buckley, S Coffey, CS Foster, E Mendick, S Seibyl, J Schuff, N AF Zhang, Yu Wu, I-Wei Buckley, Shannon Coffey, Christopher S. Foster, Eric Mendick, Susan Seibyl, John Schuff, Norbert TI Diffusion Tensor Imaging of the Nigrostriatal Fibers in Parkinson's Disease SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; MRI; diffusion tensor imaging; diffusion tensor tractography; nigrostriatal pathway ID STRIATAL DOPAMINE TRANSPORTERS; SUBSTANTIA-NIGRA; BASAL GANGLIA; NEUROTROPHIC FACTOR; BRAIN; CONNECTIVITY; TRACTOGRAPHY; PROGRESSION; DISORDERS; INFUSION AB Background: Parkinson's disease (PD) is histopathologically characterized by the loss of dopamine neurons in the substantia nigra pars cornpacta. The depletion of these neurons is thought to reduce the dopaminergic function of the nigrostriatal pathway, as well as the neural fibers that link the substantia nigra to the striatum (putamen and caudate), causing a dysregulation in striatal activity that ultimately leads to lack of movement control. Based on diffusion tensor imaging, visualizing this pathway and measuring alterations of the fiber integrity remain challenging. The objectives were to 1) develop a diffusion tensor tractography protocol for reliably tracking the nigrostriatal fibers on multicenter data; 2) test whether the integrities measured by diffusion tensor imaging of the nigrostriatal fibers are abnormal in PD; and 3) test whether abnormal integrities of the nigrostriatal fibers in PD patients are associated with the severity of motor disability and putarninal dopamine binding ratios. Methods: Diffusion tensor tractography was performed on 50 drug-naive PD patients and 27 healthy control subjects from the international multicenter Parkinson's Progression Marker Initiative. Results: Tractography consistently detected the nigrostriatal fibers, yielding reliable diffusion measures. Fractional anisotropy, along with radial and axial diffusivity of the nigrostriatal tract, showed systematic abnormalities in patients. In addition, variations in fractional anisotropy and radial diffusivity of the nigrostriatal tract were associated with the degree of motor deficits in PD patients. Conclusion: Taken together, the findings imply that the diffusion tensor imaging characteristic of the nigrostriatal tract is potentially an index for detecting and staging of early PD. 2015 International Parkinson and Movement Disorder Society C1 [Zhang, Yu; Wu, I-Wei; Buckley, Shannon; Schuff, Norbert] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94121 USA. [Zhang, Yu; Wu, I-Wei; Buckley, Shannon; Schuff, Norbert] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Coffey, Christopher S.; Foster, Eric] Univ Iowa, Coll Publ Hlth, Dept Biostat, Iowa City, IA USA. [Mendick, Susan; Seibyl, John] IND, New Haven, CT USA. [Mendick, Susan; Seibyl, John] Mol NeuroImaging LLC MNI, New Haven, CT USA. RP Zhang, Y (reprint author), Vet Adm Med Ctr, Ctr Imaging Neurodegenerat Dis, 4150 Clement St,Mail Stop 114M, San Francisco, CA 94121 USA. EM Yu.Zhang@ucsf.edu FU Parkinson's Progression Marker Initiative (PPMI) group; Michael J. Fox Foundation for Parkinson's Research (MJFF); MJFF; Abbot; Avid Radiopharmaceuticals; Biogen Idec; Bristol-Myers Squibb; Covance; Elan Corporation; Eli Lilly Co.; F. Hoffman-La Roche, Ltd.; GE Healthcare; Genentech; GlaxoSmithKline; Lundbeck; Merck; MesoScale; Pfizer; UCB; NIH [P41 EB015904] FX The study was supported by the funding partners of the Parkinson's Progression Marker Initiative (PPMI) group. PPMI is sponsored by the Michael J. Fox Foundation for Parkinson's Research (MJFF) and is co-funded by MJFF, Abbot, Avid Radiopharmaceuticals, Biogen Idec, Bristol-Myers Squibb, Covance, Elan Corporation, Eli Lilly & Co., F. Hoffman-La Roche, Ltd., GE Healthcare, Genentech, GlaxoSmithKline, Lundbeck, Merck, MesoScale, Pfizer and UCB. The study was also supported by an NIH grant (P41 EB015904). NR 39 TC 11 Z9 11 U1 2 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 2015 VL 30 IS 9 BP 1229 EP 1236 DI 10.1002/mds.26251 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA CQ7BY UT WOS:000360759000012 PM 25920732 ER PT J AU Lebois, LAM Papies, EK Gopinath, K Cabanban, R Quigley, KS Krishnamurthy, V Barrett, LF Barsalou, LW AF Lebois, Lauren A. M. Papies, Esther K. Gopinath, Kaundinya Cabanban, Romeo Quigley, Karen S. Krishnamurthy, Venkatagiri Barrett, Lisa Feldman Barsalou, Lawrence W. TI A shift in perspective: Decentering through mindful attention to imagined stressful events SO NEUROPSYCHOLOGIA LA English DT Article DE Decentering; Mental simulation; Mindfulness; Neuroimaging; Self; Stress ID DEFAULT NETWORK; MEDITATION PRACTITIONERS; PERSEVERATIVE COGNITION; FUNCTIONAL CONNECTIVITY; CARDIOVASCULAR-DISEASE; COMMITMENT THERAPY; BRAIN IMAGES; SELF; EMOTION; CORTEX AB Ruminative thoughts about a stressful event can seem subjectively real, as if the imagined event were happening in the moment. One possibility is that this subjective realism results from simulating the self as engaged in the stressful event (immersion). If so, then the process of decentering-disengaging the self from the event should reduce the subjective realism associated with immersion, and therefore perceived stressfulness. To assess this account of decentering, we taught non-meditators a strategy for disengaging from imagined events, simply viewing these events as transient mental states (mindful attention). In a subsequent neuroimaging session, participants imagined stressful and non-stressful events, while either immersing themselves or adopting mindful attention. In conjunction analyses, mindful attention down-regulated the processing of stressful events relative to baseline, whereas immersion up-regulated their processing. In direct contrasts between mindful attention and immersion, mindful attention showed greater activity in brain areas associated with perspective shifting and effortful attention, whereas immersion showed greater activity in areas associated with self-processing and visceral states. These results suggest that mindful attention produces decentering by disengaging embodied senses of self from imagined situations so that affect does not develop. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Lebois, Lauren A. M.; Barsalou, Lawrence W.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Lebois, Lauren A. M.] Harvard Univ, Sch Med, McLean Hosp, Belmont, MA 02478 USA. [Papies, Esther K.] Univ Utrecht, Dept Social & Org Psychol, NL-3508 TC Utrecht, Netherlands. [Gopinath, Kaundinya; Cabanban, Romeo; Krishnamurthy, Venkatagiri] Emory Sch Med, Ctr Syst Imaging, Atlanta, GA USA. [Quigley, Karen S.; Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA USA. [Quigley, Karen S.] Edith Nourse Rogers Mem Bedford VA Hosp, Bedford, MA USA. [Barrett, Lisa Feldman] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Lebois, LAM (reprint author), Harvard Univ, Sch Med, McLean Hosp, Belmont, MA 02478 USA. EM llebois@mclean.harvard.edu OI Papies, Esther K./0000-0002-8460-675X FU National Center for Complementary and Integrative Health, United States at the National Institute of Health [1 F31 AT007130-01, 5 F31 AT007130-02]; National Institute of Health Director's Pioneer Award [DPI OD003312] FX This work was supported by the National Center for Complementary and Integrative Health, United States at the National Institute of Health with a predoctoral Ruth L. Kirschstein National Research Service Award to LAML at Emory University (Grant numbers 1 F31 AT007130-01, 5 F31 AT007130-02), and by a National Institute of Health Director's Pioneer Award to LFB at Northeastern University (Grant number DPI OD003312), with a sub-contract to LWB at Emory University. NR 121 TC 6 Z9 6 U1 4 U2 20 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 2015 VL 75 BP 505 EP 524 DI 10.1016/j.neuropsychologia.2015.05.030 PG 20 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA CQ4TE UT WOS:000360596700048 PM 26111487 ER PT J AU Zabora, J Buzaglo, J Kennedy, V Richards, T Schapmire, T Zebrack, B Ghobrial, IM AF Zabora, James Buzaglo, Joanne Kennedy, Vicki Richards, Tiffany Schapmire, Tara Zebrack, Brad Ghobrial, Irene M. TI Clinical perspective: Linking psychosocial care to the disease continuum in patients with multiple myeloma SO PALLIATIVE & SUPPORTIVE CARE LA English DT Article DE Psychosocial care; Distress; Multiple myeloma; Standard of care ID QUALITY-OF-LIFE; NURSE LEADERSHIP BOARD; ADULT CANCER-PATIENTS; STEM-CELL TRANSPLANTATION; INTERVENTION; METAANALYSIS; HEALTH; EXPERIENCES; CAREGIVERS; SURVIVORS AB Objective: A model of psychosocial care specific for patients with multiple myeloma and their caregivers has not yet been proposed. We sought to develop a model of care that considers the specific profile of this disease. Method: The authors, representing amultidisciplinary care team, met in December of 2012 to identify a model of psychosocial care for patients with multiple myeloma and their caregivers. This model was determined by consensus during the meeting and via total agreement following the meeting. The meeting was sponsored by Onyx Pharmaceuticals. Results: The need for targeted psychosocial care for the multiple myeloma patient and caregiver throughout the disease process is essential to ensure quality of life and optimal treatment outcomes. We propose herein the first known model of care for the treatment of multiple myeloma that engages both the patient and their caregivers. Significance of results: Innovative partnerships between psychosocial providers and other entities such as pharmaceutical companies can maximize resources for comprehensive program development. This manuscript proposes a model of care that promotes active engagement in therapies for multiple myeloma while engaging the individual patient and their family caregivers. This treatment approach must be evidence based in terms of distress screening tools, comprehensive psychosocial assessments, and, most importantly, in the interventions and measurements of response that clinicians apply to this population. C1 [Zabora, James] Inova Hlth Syst, Life Canc, Fairfax, VA 22042 USA. [Buzaglo, Joanne; Kennedy, Vicki] Canc Support Community, Washington, DC USA. [Richards, Tiffany] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Schapmire, Tara] Univ Louisville, Sch Med, Louisville, KY 40292 USA. [Zebrack, Brad] Univ Michigan, Sch Social Work, Ann Arbor, MI 48109 USA. [Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Zabora, J (reprint author), Inova Hlth Syst, Life Canc, 8110 Gatehouse Rd, Fairfax, VA 22042 USA. EM James.Zabora@inova.org RI Schapmire, Tara/D-8301-2012 OI Schapmire, Tara/0000-0002-8681-8975 FU Onyx Pharmaceuticals FX The authors would like to gratefully acknowledge Elizabeth Bilotti for her contributions to the concepts outlined herein. Editorial assistance was provided by Mark Ellis, Ph.D. (E-Squared Communications) and funded by Onyx Pharmaceuticals. NR 53 TC 1 Z9 1 U1 1 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1478-9515 EI 1478-9523 J9 PALLIAT SUPPORT CARE JI Palliat. Support Care PD AUG PY 2015 VL 13 IS 4 BP 829 EP 838 DI 10.1017/S1478951514000649 PG 10 WC Health Policy & Services SC Health Care Sciences & Services GA CQ5FQ UT WOS:000360629100001 PM 24959656 ER PT J AU Ali, SK Malakouti, M AF Ali, Sayed K. Malakouti, Mazyar TI The family meeting SO PALLIATIVE & SUPPORTIVE CARE LA English DT Editorial Material C1 [Ali, Sayed K.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Malakouti, Mazyar] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Ali, SK (reprint author), South Texas Vet Hlth Care Syst, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM Sayed.ali@va.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1478-9515 EI 1478-9523 J9 PALLIAT SUPPORT CARE JI Palliat. Support Care PD AUG PY 2015 VL 13 IS 4 BP 1135 EP 1136 DI 10.1017/S1478951514000984 PG 2 WC Health Policy & Services SC Health Care Sciences & Services GA CQ5FQ UT WOS:000360629100037 PM 25159138 ER PT J AU Xu, SP Chheda, C Ouhaddi, Y Benhaddou, H Bourhim, M Grippo, PJ Principe, DR Mascarinas, E DeCant, B Tsukamoto, H Pandol, SJ Edderkaoui, M AF Xu, Shiping Chheda, Chintan Ouhaddi, Yassine Benhaddou, Hajar Bourhim, Mouloud Grippo, Paul J. Principe, Daniel R. Mascarinas, Emman DeCant, Brian Tsukamoto, Hidekazu Pandol, Stephen J. Edderkaoui, Mouad TI Characterization of Mouse Models of Early Pancreatic Lesions Induced by Alcohol and Chronic Pancreatitis SO PANCREAS LA English DT Article DE alcohol; chronic pancreatitis; pancreatic cancer ID EPITHELIAL-MESENCHYMAL TRANSITION; STEM-CELLS; HISTONE DEACETYLASES; CARCINOMA CELLS; STELLATE CELLS; CANCER; INTERLEUKIN-6; INFLAMMATION; FIBROSIS; DIFFERENTIATION AB Objective We describe the first mouse model of pancreatic intraepithelial neoplasia (PanIN) lesions induced by alcohol in the presence and absence of chronic pancreatitis. Methods Pdx1-Cre;LSL-K-ras mice were exposed to Lieber-DeCarli alcohol diet for 6 weeks with cerulein injections. The PanIN lesions and markers of fibrosis, inflammation, histone deacetylation, epithelial-to-mesenchymal transition (EMT), and cancer stemness were measured by immunohistochemistry and Western. Results Exposure of Pdx1-Cre;LSL-K-ras mice to an alcohol diet significantly stimulated fibrosis and slightly but not significantly increased the level of PanIN lesions associated with an increase in tumor-promoting M2 macrophages. Importantly, the alcohol diet did not increase activation of stellate cells. Alcohol diet and cerulein injections resulted in synergistic and additive effects on PanIN lesion and M2 macrophage phenotype induction, respectively. Cerulein pancreatitis caused stellate cell activation, EMT, and cancer stemness in the pancreas. Pancreatitis caused histone deacetylation, which was promoted by the alcohol diet. Pancreatitis increased EMT and cancer stemness markers, which were not further affected by the alcohol diet. Conclusions The results suggest that alcohol has independent effects on promotion of PDAC associated with fibrosis formed through a stellate cell-independent mechanism and that it further promotes early PDAC and M2 macrophage induction in the context of chronic pancreatitis. C1 [Xu, Shiping; Pandol, Stephen J.; Edderkaoui, Mouad] Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Xu, Shiping] Peoples Liberat Army Gen Hosp, Dept Gastroenterol, Nanlou Div, Beijing, Peoples R China. [Chheda, Chintan; Ouhaddi, Yassine; Benhaddou, Hajar; Pandol, Stephen J.; Edderkaoui, Mouad] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. [Chheda, Chintan; Ouhaddi, Yassine; Benhaddou, Hajar; Pandol, Stephen J.; Edderkaoui, Mouad] Cedars Sinai Med Ctr, Dept Biol Sci, Los Angeles, CA 90048 USA. [Ouhaddi, Yassine; Benhaddou, Hajar; Bourhim, Mouloud] Univ Mohamed Ben Abdellah, Fac Sci Dhar el Mehraz, Fes, Morocco. [Grippo, Paul J.; Principe, Daniel R.; Mascarinas, Emman; DeCant, Brian] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Grippo, Paul J.; Principe, Daniel R.; Mascarinas, Emman; DeCant, Brian] Univ Illinois, Dept Med, Chicago, IL USA. [Tsukamoto, Hidekazu] Univ So Calif, Keck Sch Med, Southern Calif Res Ctr ALPD & Cirrhosis, Los Angeles, CA 90033 USA. RP Edderkaoui, M (reprint author), 8700 Beverly Blvd,Davis Bldg,Suite 3100, Los Angeles, CA 90048 USA. EM mouad.edderkaoui@cshs.org FU National Institute on Alcohol Abuse and Alcoholism [K01AA019996]; National Cancer Institute [P01CA163200]; Department of Veterans Affairs; [P50AA011999] FX This study was supported by the National Institute on Alcohol Abuse and Alcoholism grant K01AA019996 (M.E.), the P50AA011999 grant (H.T.), the National Cancer Institute grant P01CA163200 (S.J.P.), and Merit Review awards from the Department of Veterans Affairs (S.J.P., H.T.). NR 40 TC 2 Z9 2 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD AUG PY 2015 VL 44 IS 6 BP 882 EP 887 DI 10.1097/MPA.0000000000000380 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CQ5FL UT WOS:000360628600005 PM 26166469 ER PT J AU Mokry, LE Ross, S Ahmad, OS Forgetta, V Smith, GD Leong, A Greenwood, CMT Thanassoulis, G Richards, JB AF Mokry, Lauren E. Ross, Stephanie Ahmad, Omar S. Forgetta, Vincenzo Smith, George Davey Leong, Aaron Greenwood, Celia M. T. Thanassoulis, George Richards, J. Brent TI Vitamin D and Risk of Multiple Sclerosis: A Mendelian Randomization Study SO PLOS MEDICINE LA English DT Article ID D-BINDING PROTEIN; DIAGNOSTIC-CRITERIA; CARDIOVASCULAR-DISEASE; 25-HYDROXYVITAMIN D; METABOLITE LEVELS; GENETIC-VARIANTS; BLOOD-PRESSURE; METAANALYSIS; EPIDEMIOLOGY; ASSOCIATION AB Background Observational studies have demonstrated an association between decreased vitamin D level and risk of multiple sclerosis (MS); however, it remains unclear whether this relationship is causal. We undertook a Mendelian randomization (MR) study to evaluate whether genetically lowered vitamin D level influences the risk of MS. Methods and Findings We identified single nucleotide polymorphisms (SNPs) associated with 25-hydroxyvitamin D (25OHD) level from SUNLIGHT, the largest (n = 33,996) genome-wide association study to date for vitamin D. Four SNPs were genome-wide significant for 25OHD level (p-values ranging from 6 x 10(-10) to 2 x 10(-109)), and all four SNPs lay in, or near, genes strongly implicated in separate mechanisms influencing 25OHD. We then ascertained their effect on 25OHD level in 2,347 participants from a population-based cohort, the Canadian Multicentre Osteoporosis Study, and tested the extent to which the 25OHD-decreasing alleles explained variation in 25OHD level. We found that the count of 25OHD-decreasing alleles across these four SNPs was strongly associated with lower 25OHD level (n = 2,347, F-test statistic = 49.7, p = 2.4 x 10(-12)). Next, we conducted an MR study to describe the effect of genetically lowered 25OHD on the odds of MS in the International Multiple Sclerosis Genetics Consortium study, the largest genetic association study to date for MS (including up to 14,498 cases and 24,091 healthy controls). Alleles were weighted by their relative effect on 25OHD level, and sensitivity analyses were performed to test MR assumptions. MR analyses found that each genetically determined one-standard-deviation decrease in log-transformed 25OHD level conferred a 2.0-fold increase in the odds of MS (95% CI: 1.7-2.5; p = 7.7 x 10(-12); I-2 = 63%, 95% CI: 0%-88%). This result persisted in sensitivity analyses excluding SNPs possibly influenced by population stratification or pleiotropy (odds ratio [OR] = 1.7, 95% CI: 1.3-2.2; p = 2.3 x 10(-5); I-2 = 47%, 95% CI: 0%-85%) and including only SNPs involved in 25OHD synthesis or metabolism (ORsynthesis = 2.1, 95% CI: 1.6-2.6, p = 1 x 10(-9); ORmetabolism = 1.9, 95% CI: 1.3-2.7, p = 0.002). While these sensitivity analyses decreased the possibility that pleiotropy may have biased the results, residual pleiotropy is difficult to exclude entirely. Conclusions A genetically lowered 25OHD level is strongly associated with increased susceptibility to MS. Whether vitamin D sufficiency can delay, or prevent, MS onset merits further investigation in long-term randomized controlled trials. C1 [Mokry, Lauren E.; Ross, Stephanie; Ahmad, Omar S.; Forgetta, Vincenzo; Richards, J. Brent] McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Ctr Clin Epidemiol,Dept Epidemiol, Montreal, PQ H3T 1E2, Canada. [Ahmad, Omar S.; Forgetta, Vincenzo; Thanassoulis, George; Richards, J. Brent] McGill Univ, Dept Med, Montreal, PQ, Canada. [Smith, George Davey] Univ Bristol, MRC Integrat Epidemiol Unit, Sch Social & Community Med, Bristol, Avon, England. [Leong, Aaron] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Leong, Aaron] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Greenwood, Celia M. T.] McGill Univ, Dept Oncol, Montreal, PQ, Canada. [Greenwood, Celia M. T.; Richards, J. Brent] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada. [Greenwood, Celia M. T.; Richards, J. Brent] McGill Univ, Dept Human Genet, Montreal, PQ, Canada. [Greenwood, Celia M. T.] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada. [Thanassoulis, George] McGill Univ, Ctr Hlth, Prevent & Genom Cardiol, Montreal, PQ, Canada. [Richards, J. Brent] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. RP Mokry, LE (reprint author), McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Ctr Clin Epidemiol,Dept Epidemiol, Montreal, PQ H3T 1E2, Canada. EM brent.richards@mcgill.ca RI Davey Smith, George/A-7407-2013; OI Davey Smith, George/0000-0002-1407-8314; Forgetta, Vincenzo/0000-0002-6061-4720 FU Canadian Institute of Health Research; Fonds de la Recherche en Sante Quebec [MOP-119462]; Lady Davis Institute; Jewish General Hospital; Canadian Diabetes Association Postdoctoral Fellowship FX JBR is funded by the Canadian Institute of Health Research (http://www.cihr-irsc.gc.ca/e/193.html), (MOP-119462) The Fonds de la Recherche en Sante Quebec, the Lady Davis Institute, and the Jewish General Hospital. AL is supported by the Canadian Diabetes Association Postdoctoral Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 56 TC 40 Z9 40 U1 4 U2 21 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 2015 VL 12 IS 8 AR e1001866 DI 10.1371/journal.pmed.1001866 PG 20 WC Medicine, General & Internal SC General & Internal Medicine GA CQ6IP UT WOS:000360708300008 PM 26305103 ER PT J AU Wargo, JA Reuben, A Cooper, ZA Oh, KS Sullivan, RJ AF Wargo, Jennifer A. Reuben, Alexandre Cooper, Zachary A. Oh, Kevin S. Sullivan, Ryan J. TI Immune Effects of Chemotherapy, Radiation, and Targeted Therapy and Opportunities for Combination With Immunotherapy SO SEMINARS IN ONCOLOGY LA English DT Review ID RENAL-CELL CARCINOMA; HIGH-DOSE INTERLEUKIN-2; RISK MELANOMA PATIENTS; HUMAN DENDRITIC CELLS; DOUBLE-STRAND BREAKS; METASTATIC MELANOMA; BRAF INHIBITION; T-CELLS; INTERFERON-ALPHA; ACQUIRED-RESISTANCE AB There have been significant advances in cancer treatment over the past several years through the use of chemotherapy, radiation therapy, molecularly targeted therapy, and immunotherapy. Despite these advances, treatments such as monotherapy or monomodality have significant limitations. There is increasing interest in using these strategies in combination; however, it is not completely clear how best to incorporate molecularly targeted and immune-targeted therapies into combination regimens. This is particularly pertinent when considering combinations with immunotherapy, as other types of therapy may have significant impact on host immunity, the tumor microenvironment, or both. Thus, the influence of chemotherapy, radiation therapy, and molecularly targeted therapy on the host anti-tumor immune response and the host anti-host response (ie, autoimmune toxicity) must be taken into consideration when designing immunotherapy-based combination regimens. We present data related to many of these combination approaches in the context of investigations in patients with melanoma and discuss their potential relationship to management of patients with other tumor types. Importantly, we also highlight challenges of these approaches and emphasize the need for continued translational research. (C) 2015 Elsevier Inc. All rights reserved. C1 [Wargo, Jennifer A.; Reuben, Alexandre; Cooper, Zachary A.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Wargo, Jennifer A.; Cooper, Zachary A.] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA. [Oh, Kevin S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Oh, Kevin S.; Sullivan, Ryan J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Sullivan, Ryan J.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. RP Sullivan, RJ (reprint author), Massachusetts Gen Hosp, Dept Med Oncol, 55 Fruit St, Boston, MA 02114 USA. EM rsullivan7@mgh.harvard.edu FU NIH [1K08CA160692-01A1, U54CA163125-01] FX J.A.W. acknowledges NIH grants 1K08CA160692-01A1, U54CA163125-01, and the generous philanthropic support of several families whose lives have been affected by melanoma. NR 129 TC 9 Z9 10 U1 1 U2 16 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 EI 1532-8708 J9 SEMIN ONCOL JI Semin. Oncol. PD AUG PY 2015 VL 42 IS 4 BP 601 EP 616 DI 10.1053/j.seminoncol.2015.05.007 PG 16 WC Oncology SC Oncology GA CQ7KF UT WOS:000360782200009 PM 26320064 ER PT J AU Baggish, AL AF Baggish, Aaron L. TI Mechanisms underlying the cardiac benefits of exercise: Still running in the dark SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Editorial Material ID SEDENTARY BEHAVIOR; PHYSICAL-ACTIVITY; RISK C1 Massachusetts Gen Hosp, Cardiovasc Performance Program, Boston, MA 02114 USA. RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Cardiovasc Performance Program, Boston, MA 02114 USA. EM abaggish@partners.org FU NHLBI NIH HHS [R01-HL-117037]; NIDA NIH HHS [R01-DA-029141] NR 7 TC 2 Z9 2 U1 1 U2 3 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD AUG PY 2015 VL 25 IS 6 BP 537 EP 539 DI 10.1016/j.tcm.2015.01.006 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CQ0XK UT WOS:000360321700012 PM 25795335 ER PT J AU Gothe, H Schall, I Saverno, K Mitrovic, M Luzak, A Brixner, D Siebert, U AF Gothe, H. Schall, I. Saverno, K. Mitrovic, M. Luzak, A. Brixner, D. Siebert, U. TI The Impact of Generic Substitution on Health and Economic Outcomes: A Systematic Review SO APPLIED HEALTH ECONOMICS AND HEALTH POLICY LA English DT Review ID KIDNEY-TRANSPLANT RECIPIENTS; BRAND-NAME; ANTIEPILEPTIC DRUGS; CARDIOVASCULAR-DISEASE; RESOURCE UTILIZATION; ATRIAL-FIBRILLATION; UNITED-STATES; EFFICACY; WARFARIN; SAFETY AB Background Generic drugs are considered therapeutically equivalent to their original counterparts and lower in acquisition costs. However, the overall impact of generic substitution (GS) on global clinical and economic outcomes has not been conclusively evaluated. Objective To test whether (1) generics and original products yield the same health outcomes, and (2) generic therapies save economic resources versus original therapies. Methods We performed a systematic literature review in Medline, Embase, and the Cochrane Database of Systematic Reviews to identify original studies that examine clinical or economic outcomes of GS. After standardized data extraction, reported outcomes were categorized as supporting or rejecting the hypotheses. Each reported outcome was assessed and accounted for supporting and opposing GS. One publication could provide multiple outcome comparisons. Results We included 40 studies across ten therapeutic areas. Fourteen studies examined patients on de novo therapy; 24 studies investigated maintenance drug therapy, and two studies considered both settings. Overall, 119 outcome comparisons were examined. Of 97 clinical outcome comparisons, 67 % reported no significant difference between generic drugs and their off-patent counterparts. Of 22 economic comparisons, 64 % suggested that GS increased costs. Consequently, hypothesis (1) was supported but hypothesis (2) was not. We found no major differences among studies that investigated clinical outcomes with de novo or maintenance therapy. Conclusion The review suggests that clinical effects are similar after GS. However, economic savings are not guaranteed. More systematic research comparing clinical and economic outcomes with or without GS is needed to inform policy on the use of generic substitution. C1 [Gothe, H.; Schall, I.; Saverno, K.; Mitrovic, M.; Luzak, A.; Brixner, D.; Siebert, U.] Univ Hlth Sci Med Informat & Technol, Inst Publ Hlth Med Decis Making & Hlth Technol As, Dept Publ Hlth & Hlth Technol Assessment, UMIT,Eduard Wallnoefer Ctr 1, A-6060 Hall In Tirol, Austria. [Gothe, H.] Ctr Personalized Canc Med Innsbruck, ONCOTYROL, Div Publ Hlth Decis Modelling Hlth Technol Assess, A-6020 Innsbruck, Austria. [Gothe, H.] Tech Univ Dresden, Dresden Med Sch Carl Gustav Carus, D-01307 Dresden, Germany. [Saverno, K.; Brixner, D.] Univ Utah, Dept Pharmacotherapy, Salt Lake City, UT 84112 USA. [Siebert, U.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Hlth Decis Sci, Boston, MA 02115 USA. [Siebert, U.] Harvard Univ, Sch Med, Dept Radiol, Inst Technol Assessment,Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Siebert, U (reprint author), Univ Hlth Sci Med Informat & Technol, Inst Publ Hlth Med Decis Making & Hlth Technol As, Dept Publ Hlth & Hlth Technol Assessment, UMIT,Eduard Wallnoefer Ctr 1, A-6060 Hall In Tirol, Austria. EM uwe.siebert@umit.at FU Abbott (Allschwil, Switzerland) FX This study was in part funded by Abbott (Allschwil, Switzerland). We would like to thank Anke-Peggy Holtorf and Zoltan Kalo for their scientific input. NR 54 TC 5 Z9 5 U1 0 U2 4 PU SPRINGER INTERNATIONAL PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1175-5652 EI 1179-1896 J9 APPL HEALTH ECON HEA JI Appl. Health Econ. Health Policy PD AUG PY 2015 VL 13 IS 1 SU S BP S21 EP S33 DI 10.1007/s40258-014-0147-0 PG 13 WC Health Policy & Services SC Health Care Sciences & Services GA CQ2YG UT WOS:000360467900004 PM 26091709 ER PT J AU Motai, Y Ma, D Docef, A Yoshida, H AF Motai, Yuichi Ma, Dingkun Docef, Alen Yoshida, Hiroyuki TI Smart Colonography for Distributed Medical Databases with Group Kernel Feature Analysis SO ACM TRANSACTIONS ON INTELLIGENT SYSTEMS AND TECHNOLOGY LA English DT Article DE Algorithms; Computed tomographic colonography; distributed databases; kernel feature analysis; group learning ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; PRINCIPAL COMPONENT ANALYSIS; CT-COLONOGRAPHY; COLORECTAL-CANCER; VOLUMETRIC FEATURES; COLONIC POLYPS; CAD; CLASSIFICATION; COLONOSCOPY; CHALLENGES AB Computer-Aided Detection (CAD) of polyps in Computed Tomographic (CT) colonography is currently very limited since a single database at each hospital/institution doesn't provide sufficient data for training the CAD system's classification algorithm. To address this limitation, we propose to use multiple databases, (e.g., big data studies) to create multiple institution-wide databases using distributed computing technologies, which we call smart colonography. Smart colonography may be built by a larger colonography database networked through the participation of multiple institutions via distributed computing. The motivation herein is to create a distributed database that increases the detection accuracy of CAD diagnosis by covering many true-positive cases. Colonography data analysis is mutually accessible to increase the availability of resources so that the knowledge of radiologists is enhanced. In this article, we propose a scalable and efficient algorithm called Group Kernel Feature Analysis (GKFA), which can be applied to multiple cancer databases so that the overall performance of CAD is improved. The key idea behind the proposed GKFA method is to allow the feature space to be updated as the training proceeds with more data being fed from other institutions into the algorithm. Experimental results show that GKFA achieves very good classification accuracy. C1 [Motai, Yuichi; Ma, Dingkun; Docef, Alen] Virginia Commonwealth Univ, Dept Elect & Comp Engn, Richmond, VA 23284 USA. [Yoshida, Hiroyuki] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Yoshida, Hiroyuki] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Motai, Y (reprint author), Virginia Commonwealth Univ, Dept Elect & Comp Engn, 601 West Main St, Richmond, VA 23284 USA. EM ymotai@vcu.edu; madingkun@gmail.com; adocef@vcu.edu; Yoshida.Hiro@mgh.harvard.edu FU CAREER award from National Science Foundation [1054333]; CTSA from the National Center for Advancing Translational Sciences [UL1TR000058]; Center for Clinical and Translational Research Endowment Fund of Virginia Commonwealth University (VCU); Institutional Research Grant from the American Cancer Society through the Massey Cancer Center [IRG-73-001-31]; Presidential Research Incentive Program at VCU; National Institutes of Health [CA095279, CA166816] FX This work is supported partly by the CAREER award 1054333 from National Science Foundation, CTSA UL1TR000058 from the National Center for Advancing Translational Sciences, Center for Clinical and Translational Research Endowment Fund of Virginia Commonwealth University (VCU), Institutional Research Grant IRG-73-001-31 from the American Cancer Society through the Massey Cancer Center, Presidential Research Incentive Program at VCU, and National Institutes of Health Grants CA095279 and CA166816. NR 45 TC 0 Z9 0 U1 2 U2 6 PU ASSOC COMPUTING MACHINERY PI NEW YORK PA 2 PENN PLAZA, STE 701, NEW YORK, NY 10121-0701 USA SN 2157-6904 EI 2157-6912 J9 ACM T INTEL SYST TEC JI ACM Trans. Intell. Syst. Technol. PD AUG PY 2015 VL 6 IS 4 AR 58 DI 10.1145/2668136 PG 24 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems SC Computer Science GA CP6OR UT WOS:000360007500016 ER PT J AU Bhatia, RS Ivers, N Yin, CX Myers, D Nesbitt, G Edwards, J Yared, K Wadhera, R Wu, JC Wong, B Hansen, M Weinerman, A Shadowitz, S Johri, A Farkouh, M Thavendiranathan, P Udell, JA Rambihar, S Chow, CM Hall, J Thorpe, KE Rakowski, H Weiner, RB AF Bhatia, R. Sacha Ivers, Noah Yin, Cindy X. Myers, Dorothy Nesbitt, Gillian Edwards, Jeremy Yared, Kibar Wadhera, Rishi Wu, Justina C. Wong, Brian Hansen, Mark Weinerman, Adina Shadowitz, Steven Johri, Amer Farkouh, Michael Thavendiranathan, Paaladinesh Udell, Jacob A. Rambihar, Sherryn Chow, Chi-Ming Hall, Judith Thorpe, Kevin E. Rakowski, Harry Weiner, Rory B. TI Design and methods of the Echo WISELY (Will Inappropriate Scenarios for Echocardiography Lessen SignificantlY) study: An investigator-blinded randomized controlled trial of education and feedback intervention to reduce inappropriate echocardiograms SO AMERICAN HEART JOURNAL LA English DT Article ID APPROPRIATE USE CRITERIA; CARDIOVASCULAR IMAGING CONSORTIUM; CONTINUING MEDICAL-EDUCATION; TRANSTHORACIC ECHOCARDIOGRAPHY; STRESS ECHOCARDIOGRAPHY; TEMPORAL TRENDS; QUALITY; IMPACT AB Background Appropriate use criteria (AUC) for transthoracic echocardiography (TTE) were developed to address concerns regarding inappropriate use of TTE. A previous pilot study suggests that an educational and feedback intervention can reduce inappropriate TTEs ordered by physicians in training. It is unknown if this type of intervention will be effective when targeted at attending level physicians in a variety of clinical settings. Aims The aim of this international, multicenter study is to evaluate the hypothesis that an AUC-based educational and feedback intervention will reduce the proportion of inappropriate echocardiograms ordered by attending physicians in the ambulatory environment. Methods In an ongoing multicentered, investigator-blinded, randomized controlled trial across Canada and the United States, cardiologists and primary care physicians practicing in the ambulatory setting will be enrolled. The intervention arm will receive (1) a lecture outlining the AUC and most recent available evidence highlighting appropriate use of TTE, (2) access to the American Society of Echocardiography mobile phone app, and (3) individualized feedback reports e-mailed monthly summarizing TTE ordering behavior including information on inappropriate TTEs and brief explanations of the inappropriate designation. The control group will receive no education on TTE appropriate use and order TTEs as usual practice. Conclusions The Echo WISELY (Will Inappropriate Scenarios for Echocardiography Lessen Significantly in an education RCT) study is the first multicenter randomized trial of an AUC-based educational intervention. The study will examine whether an education and feedback intervention will reduce the rate of outpatient inappropriate TTEs ordered by attending level cardiologists and primary care physicians (www.clinicaltrials.gov identifier NCT02038101). C1 [Bhatia, R. Sacha; Ivers, Noah; Yin, Cindy X.; Udell, Jacob A.; Rambihar, Sherryn] Womens Coll Hosp, Inst Hlth Syst Solut & Virtual Care, Toronto, ON, Canada. [Bhatia, R. Sacha; Farkouh, Michael; Thavendiranathan, Paaladinesh; Rakowski, Harry] Univ Toronto, Univ Hlth Network, Peter Munk Cardiac Ctr, Toronto, ON, Canada. [Ivers, Noah; Udell, Jacob A.] Univ Toronto, Womens Coll Hosp, Dept Family & Community Med, Toronto, ON, Canada. [Ivers, Noah; Wadhera, Rishi; Wu, Justina C.; Udell, Jacob A.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Myers, Dorothy; Thorpe, Kevin E.] St Michaels Hosp, Li Ka Shing Knowledge Inst, Appl Hlth Res Ctr, Toronto, ON M5B 1W8, Canada. [Nesbitt, Gillian; Farkouh, Michael; Hall, Judith; Thorpe, Kevin E.] Mt Sinai Hosp, Cardiol Div, Toronto, ON M5G 1X5, Canada. [Edwards, Jeremy; Chow, Chi-Ming] St Michaels Hosp, Echocardiogram & Vasc Lab, Toronto, ON M5B 1W8, Canada. [Yared, Kibar] Scarborough Gen Hosp, Toronto, ON, Canada. [Wong, Brian; Hansen, Mark; Weinerman, Adina; Shadowitz, Steven] Sunnybrook Med Ctr, Toronto, ON, Canada. [Johri, Amer] Queens Univ, Kingston, ON, Canada. [Weiner, Rory B.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Bhatia, RS (reprint author), Univ Hlth Network, Inst Hlth Syst Solut & Virtual Care, Womens Coll Hosp, Inst Clin Evaluat Sci,Div Cardiol, Toronto, ON, Canada. RI Emchi, Karma/Q-1952-2016; OI Wadhera, Rishi/0000-0003-1089-3896 FU Peter Munk Cardiac Center at University Health Network; Ministry of Health and Long-Term Care of Ontario; Cardiac Care Network of Ontario FX This study was funded by operating grants from the Peter Munk Cardiac Center at University Health Network, the Ministry of Health and Long-Term Care of Ontario, and the Cardiac Care Network of Ontario. The opinions, results, and conclusions reported in this article are those of the authors. The funding sources had no role in the study's design or conduct. NR 23 TC 4 Z9 4 U1 1 U2 2 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 2015 VL 170 IS 2 BP 202 EP 209 DI 10.1016/j.ahj.2015.04.022 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CQ1LV UT WOS:000360360100005 PM 26299215 ER PT J AU Khazanie, P Heizer, GM Hasselblad, V Armstrong, PW Califf, RM Ezekowitz, J Dickstein, K Levy, WC McMurray, JJV Metra, M Tang, WHW Teerlink, JR Voors, AA O'Connor, CM Hernandez, AF Starling, R AF Khazanie, Prateeti Heizer, Gretchen M. Hasselblad, Vic Armstrong, Paul W. Califf, Robert M. Ezekowitz, Justin Dickstein, Kenneth Levy, Wayne C. McMurray, John J. V. Metra, Marco Tang, W. H. Wilson Teerlink, John R. Voors, Adriaan A. O'Connor, Christopher M. Hernandez, Adrian F. Starling, Randall TI Predictors of clinical outcomes in acute decompensated heart failure: Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure outcome models SO AMERICAN HEART JOURNAL LA English DT Article ID NATIONAL REGISTRY ADHERE; WORSENING RENAL-FUNCTION; RISK STRATIFICATION; OPTIMIZE-HF; MORTALITY; IMPACT; TRIAL; HYPONATREMIA; ADMISSION; SURVIVAL AB Background Patients hospitalized for acute decompensated heart failure (ADHF) are at high risk for early mortality and rehospitalization. Risk stratification of ADHF using clinically available data on admission is increasingly important to integrate with clinical pathways. Our goal was to create a simple method of screening patients upon admission to identify those with increased risk of future adverse events. Methods Using ASCEND-HF, a pragmatic clinical trial conducted in 398 sites globally, we developed and validated logistic regression risk models for (a) 30-day mortality/HF rehospitalization, (b) 30-day mortality/all-cause rehospitalization, (c) 30-day all-cause mortality, and (d) 180-day all-cause mortality. Fifty-one candidate variables were evaluated based on prior publications and clinical review. Final models were selected based on stepwise selection with entry and a staying criterion of P < .01. The 30-day mortality model was externally validated, and coefficients were converted to an additive risk score. Results Among 7,141 patients, the median age was 67 years, 34% were female, and 80% had a left ventricular ejection fraction <40%. The models had between 5 and 12 risk factors with c-indices ranging from 0.68 to 0.75. A simplified score, including age, systolic blood pressure, sodium, blood urea nitrogen, and dyspnea at rest, discriminated 30-day mortality risk from 0.5% (score 0) to 53% (score 10). Conclusions Commonly available clinical variables provide simple risk stratification for clinical outcomes among patients with ADHF, and these models may be considered for integration into routine clinical care. C1 [Khazanie, Prateeti; Heizer, Gretchen M.; Hasselblad, Vic; Califf, Robert M.; O'Connor, Christopher M.; Hernandez, Adrian F.] Duke Clin Res Inst, Durham, NC 27715 USA. [Khazanie, Prateeti; Califf, Robert M.; O'Connor, Christopher M.; Hernandez, Adrian F.] Duke Univ, Sch Med, Durham, NC USA. [Armstrong, Paul W.; Ezekowitz, Justin] Univ Alberta, Canadian VIGOUR Ctr, Edmonton, AB, Canada. [Dickstein, Kenneth] Univ Bergen, Stavenger Univ Hosp, Bergen, Norway. [Levy, Wayne C.] Univ Washington, Med Ctr, Seattle, WA 98195 USA. [McMurray, John J. V.] Univ Glasgow, British Heart Fdn Cardiovasc Res Ctr, Glasgow, Lanark, Scotland. [Metra, Marco] Univ Brescia, Inst Cardiol, Brescia, Italy. [Tang, W. H. Wilson; Starling, Randall] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. [Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. RP Khazanie, P (reprint author), Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. EM prateeti.khazanie@duke.edu RI Hernandez, Adrian F./A-7818-2016; OI Hernandez, Adrian F./0000-0003-3387-9616; Metra, Marco/0000-0001-6691-8568; mcmurray, john/0000-0002-6317-3975 FU Scios FX ASCEND-HF was supported by Scios. NR 34 TC 10 Z9 10 U1 1 U2 7 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 2015 VL 170 IS 2 BP 290 EP U128 DI 10.1016/j.ahj.2015.04.006 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CQ1LV UT WOS:000360360100016 PM 26299226 ER PT J AU Corrales-Medina, VF Taljaard, M Yende, S Kronmal, R Dwivedi, G Newman, AB Elkind, MSV Lyles, MF Chirinos, JA AF Corrales-Medina, Vicente F. Taljaard, Monica Yende, Sachin Kronmal, Richard Dwivedi, Girish Newman, Anne B. Elkind, Mitchell S. V. Lyles, Mary F. Chirinos, Julio A. TI Intermediate and long-term risk of new-onset heart failure after hospitalization for pneumonia in elderly adults SO AMERICAN HEART JOURNAL LA English DT Article ID COMMUNITY-ACQUIRED PNEUMONIA; INFLAMMATORY MARKERS; EJECTION FRACTION; OLDER AMERICANS; MORTALITY; EPIDEMIOLOGY; FRACTURE; SEPSIS; ASSOCIATION; MORBIDITY AB Background Pneumonia is associated with high risk of heart failure (HF) in the short term (30 days) postinfection. Whether this association persists beyond this period is unknown. Methods We studied 5,613 elderly (>= 65 years) adults enrolled in the Cardiovascular Health Study between 1989 and 1994 at 4 US communities. Participants had no clinical diagnosis of HF at enrollment, and they were followed up through December 2010. Hospitalizations for pneumonia were identified using validated International Classification of Disease Ninth Revision codes. A centralized committee adjudicated new-onset HF events. Using Cox regression, we estimated adjusted hazard ratios (HRs) of new-onset HF at different time intervals after hospitalization for pneumonia. Results A total of 652 participants hospitalized for pneumonia during follow-up were still alive and free of clinical diagnosis of HF by day 30 posthospitalization. Relative to the time of their hospitalization, new-onset HF occurred in 22 cases between 31 and 90 days (HR 6.9, 95% CI 4.46-10.63, P < .001), 14 cases between 91 days and 6 months (HR 3.2, 95% CI 1.88-5.50, P < .001), 20 cases between 6 months and 1 year (HR 2.6, 95% CI 1.64-4.04, P < .001), 76 cases between 1 and 5 years (HR 1.7, 95% CI 1.30-2.12, P < .001), and 71 cases after 5 years (HR 2.0, 95% CI 1.56-2.58, P < .001). Results were robust to sensitivity analyses using stringent definitions of pneumonia and extreme assumptions for potential informative censoring. Conclusion Hospitalization for pneumonia is associated with increased risk of new-onset HF in the intermediate and long term. Studies should characterize the mechanisms of this association in order to prevent HF in elderly pneumonia survivors. C1 [Corrales-Medina, Vicente F.; Taljaard, Monica; Dwivedi, Girish] Ottawa Hosp Res Inst, Ottawa, ON, Canada. [Corrales-Medina, Vicente F.; Dwivedi, Girish] Univ Ottawa, Dept Med, Ottawa, ON K1Y 4E9, Canada. [Taljaard, Monica] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON K1Y 4E9, Canada. [Yende, Sachin] Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA USA. [Kronmal, Richard] Univ Washington, Dept Stat, Seattle, WA 98195 USA. [Dwivedi, Girish] Univ Ottawa, Inst Heart, Ottawa, ON K1Y 4E9, Canada. [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Elkind, Mitchell S. V.] Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. [Elkind, Mitchell S. V.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Lyles, Mary F.] Wake Forest Univ, Dept Med, Winston Salem, NC 27109 USA. [Chirinos, Julio A.] Univ Penn, Philadelphia, PA 19104 USA. [Chirinos, Julio A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Corrales-Medina, VF (reprint author), Univ Ottawa, Dept Med, 1053 Carling Ave,CPC 470, Ottawa, ON K1Y 4E9, Canada. EM vcorrales@toh.on.ca RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Corrales-Medina, Vicente/0000-0002-9691-491X FU National Heart, Lung, and Blood Institute [HL080295, HHSN268201200036C, HHSN268200800007C, N01 HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086]; National Institute of Neurological Disorders and Stroke; National Institute on Aging [AG023629]; Department of Medicine of The Ottawa Hospital; Ottawa Hospital Research Institute in Ottawa, Ontario, Canada; [K23GM083215] FX CHS was supported by contracts HHSN268201200036C, HHSN268200800007C, N01 HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086 and Grant HL080295 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided by AG023629 from the National Institute on Aging. A full list of principal CHS investigators and institutions can be found at CHS-NHLB.org. Dr Corrales-Medina is supported by a Recruitment Award from the Department of Medicine of The Ottawa Hospital and the Ottawa Hospital Research Institute in Ottawa, Ontario, Canada. Dr Yende is supported by K23GM083215. NR 38 TC 8 Z9 8 U1 0 U2 0 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 2015 VL 170 IS 2 BP 306 EP U149 DI 10.1016/j.ahj.2015.04.028 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CQ1LV UT WOS:000360360100018 PM 26299228 ER PT J AU Jones, WS Patel, MR Tsai, TT Go, AS Gupta, R Hedayati, N Ho, PM Jazaeri, O Rehring, TF Rogers, RK Shetterly, SM Wagner, NM Magid, DJ AF Jones, W. Schuyler Patel, Manesh R. Tsai, Thomas T. Go, Alan S. Gupta, Rajan Hedayati, Nasim Ho, P. Michael Jazaeri, Omid Rehring, Thomas F. Rogers, R. Kevin Shetterly, Susan M. Wagner, Nicole M. Magid, David J. TI Anatomic runoff score predicts cardiovascular outcomes in patients with lower extremity peripheral artery disease undergoing revascularization SO AMERICAN HEART JOURNAL LA English DT Article ID ANKLE-BRACHIAL INDEX; CRITICAL LIMB ISCHEMIA; MYOCARDIAL-INFARCTION; SUPERVISED EXERCISE; VASCULAR-SURGERY; BYPASS-SURGERY; HIGH MORTALITY; ANGIOPLASTY; THERAPY; INTERVENTIONS AB Background Although the presence, extent, and severity of obstruction in patients with lower extremity peripheral artery disease (LE PAD) affect their functional status, quality of life, and treatment, it is not known if these factors are associated with future cardiovascular events. We empirically created an anatomic runoff score (ARS) to approximate the burden of LE PAD and determined its association with clinical outcomes. Methods We evaluated all patients with LE PAD and bilateral angiography undergoing revascularization in a community-based clinical study. Primary clinical outcomes of interest were (1) a composite of all-cause death, myocardial infarction (MI), and stroke and (2) amputation-free survival. Cox proportional hazards models were created to identify predictors of clinical outcomes. Results We evaluated 908 patients undergoing angiography, and a total of 260 (28.0%) patients reached the composite end point (45 MI, 63 stroke, and 152 death) during the study period. Anatomic runoff score ranged from 0 to 15 (mean 4.7; SD 2.5) with higher scores indicating a higher burden of disease, and an optimal cutpoint analysis classified patients into low ARS (<5) and high ARS (>= 5). The unadjusted rates of the primary composite end point and amputation-free survival were nearly 2-fold higher in patients with a high ARS when compared with patients with a low ARS. The most significant predictors of the composite end point (death/MI/stroke) were age (delta 10 years; hazard ratio [HR] 1.53; CI 1.32-1.78; P < .001), diabetes mellitus (HR 1.65; CI 1.26-2.18; P < .001), glomerular filtration rate <30 (HR 2.23; CI 1.44-3.44; P < .001), statin use (HR 0.66; CI 0.48-0.88; P < .001), and ARS (d 2 points; HR 1.21; CI 1.08-1.35; P < .001). Conclusions After adjustment for clinical factors, the LE PAD ARS was an independent predictor of future cardiovascular morbidity and mortality in a broadly representative patient population undergoing revascularization for symptomatic PAD. A clinically useful anatomic scoring system, if validated, may assist clinicians in risk stratification during the course of clinical decision making. C1 [Jones, W. Schuyler; Patel, Manesh R.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27710 USA. [Jones, W. Schuyler; Patel, Manesh R.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Tsai, Thomas T.; Ho, P. Michael; Rehring, Thomas F.] Kaiser Permanente Colorado, Div Cardiol, Denver, CO USA. [Go, Alan S.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Tsai, Thomas T.; Gupta, Rajan; Ho, P. Michael; Rogers, R. Kevin] Univ Colorado, Denver, CO 80202 USA. [Hedayati, Nasim] Univ Calif Davis, Med Ctr, Div Vasc & Endovasc Surg, Sacramento, CA 95817 USA. [Ho, P. Michael] Denver VA Med Ctr, Denver, CO USA. [Jazaeri, Omid] Univ Colorado, Sect Vasc Surg, Denver, CO 80202 USA. [Magid, David J.] Colorado Permanente Med Grp, Dept Vasc Therapy, Denver, CO USA. [Tsai, Thomas T.; Shetterly, Susan M.; Wagner, Nicole M.; Magid, David J.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. RP Jones, WS (reprint author), Duke Univ, Med Ctr, Box 3126, Durham, NC 27710 USA. EM schuyler.jones@dm.duke.edu OI Jones, William/0000-0002-7288-9596 NR 34 TC 3 Z9 3 U1 2 U2 2 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 2015 VL 170 IS 2 BP 400 EP U273 DI 10.1016/j.ahj.2015.04.026 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CQ1LV UT WOS:000360360100029 PM 26299239 ER PT J AU Jansen, H Loley, C Lieb, W Pencina, MJ Nelson, CP Kathiresan, S Peloso, GM Voight, BF Reilly, MP Assimes, TL Boerwinkle, E Hengstenberg, C Laaksonen, R McPherson, R Roberts, R Thorsteinsdottir, U Peters, A Gieger, C Rawal, R Thompson, JR Konig, IR Vasan, RS Erdmann, J Samani, NJ Schunkert, H AF Jansen, Henning Loley, Christina Lieb, Wolfgang Pencina, Michael J. Nelson, Christopher P. Kathiresan, Sekar Peloso, Gina M. Voight, Benjamin F. Reilly, Muredach P. Assimes, Themistocles L. Boerwinkle, Eric Hengstenberg, Christian Laaksonen, Reijo McPherson, Ruth Roberts, Robert Thorsteinsdottir, Unnur Peters, Annette Gieger, Christian Rawal, Rajesh Thompson, John R. Koenig, Inke R. Vasan, Ramachandran S. Erdmann, Jeanette Samani, Nilesh J. Schunkert, Heribert CA CARDIoGRAM Consortium TI Genetic variants primarily associated with type 2 diabetes are related to coronary artery disease risk SO ATHEROSCLEROSIS LA English DT Article DE Genome-wide association; Cardiovascular disease; Coronary artery disease; SNP; Type-2 diabetes ID GENOME-WIDE ASSOCIATION; CARDIOVASCULAR-DISEASE; HEART-DISEASE; MYOCARDIAL-INFARCTION; SUSCEPTIBILITY LOCUS; FASTING GLUCOSE; BLOOD-PRESSURE; MELLITUS; INSULIN; DESIGN AB Background: The mechanisms underlying the association between diabetes and coronary artery disease (CAD) risk are unclear. We aimed to assess this association by studying genetic variants that have been shown to associate with type 2 diabetes (T2DM). If the association between diabetes and CAD is causal, we expected to observe an association of these variants with CAD as well. Methods and results: We studied all genetic variants currently known to be associated with T2DM at a genome-wide significant level (p < 5*10(-8)) in CARDIoGRAM, a genome-wide data-set of CAD including 22,233 CAD cases and 64,762 controls. Out of the 44 published T2DM SNPs 10 were significantly associated with CAD in CARDIoGRAM (OR> 1, p < 0.05), more than expected by chance (p = 5.0*10(-5)). Considering all 44 SNPs, the average CAD risk observed per individual T2DM risk allele was 1.0076 (95% confidence interval (CI), 0.9973-1.0180). Such average risk increase was significantly lower than the increase expected based on i) the published effects of the SNPs on T2DM risk and ii) the effect of T2DM on CAD risk as observed in the Framingham Heart Study, which suggested a risk of 1.067 per allele (p = 7.2*10(-10) vs. the observed effect). Studying two risk scores based on risk alleles of the diabetes SNPs, one score using individual level data in 9856 subjects, and the second score on average effects of reported beta-coefficients from the entire CARDIoGRAM data-set, we again observed a significant - yet smaller than expected - association with CAD. Conclusions: Our data indicate that an association between type 2 diabetes related SNPs and CAD exists. However, the effects on CAD risk appear to be by far lower than what would be expected based on the effects of risk alleles on T2DM and the effect of T2DM on CAD in the epidemiological setting. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Jansen, Henning; Hengstenberg, Christian; Schunkert, Heribert] Tech Univ Munich, Deutsch Herzzentrum, D-80636 Munich, Germany. [Jansen, Henning; Hengstenberg, Christian; Schunkert, Heribert] Tech Univ Munich, Partner Site Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, D-80636 Munich, Germany. [Loley, Christina; Koenig, Inke R.] Med Univ Lubeck, Inst Med Biomet & Stat, D-23538 Lubeck, Germany. [Lieb, Wolfgang] Univ Kiel, Inst Epidemiol, Kiel, Germany. [Pencina, Michael J.] Duke Clin Res Inst, Dept Biostat & Bioinformat, Durham, NC USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Sect Prevent Med & Epidemiol, Boston, MA 02118 USA. [Nelson, Christopher P.; Samani, Nilesh J.] Univ Leicester, Glenfield Hosp, Dept Cardiovascular Sci, Leicester LE3 9QP, Leics, England. [Nelson, Christopher P.; Samani, Nilesh J.] Glenfield Hosp, Leicester Natl Inst, Hlth Res Biomed Res Unit Cardiovasc Dis, Leicester LE3 9QP, Leics, England. [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Kathiresan, Sekar; Peloso, Gina M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kathiresan, Sekar] Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02138 USA. [Kathiresan, Sekar; CARDIoGRAM Consortium] MIT, Cambridge, MA 02139 USA. [Voight, Benjamin F.; Reilly, Muredach P.] Univ Penn, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Assimes, Themistocles L.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Boerwinkle, Eric] Univ Texas Houston, Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Boerwinkle, Eric] Univ Texas Houston, Inst Mol Med, Houston, TX USA. [Laaksonen, Reijo] Tampere Univ Hosp, Ctr Sci, Tampere, Finland. [McPherson, Ruth; Roberts, Robert] Univ Ottawa, John & Jennifer Ruddy Canadian Cardiovasc Genet C, Inst Heart, Ottawa, ON, Canada. [Thorsteinsdottir, Unnur] DeCODE Genet, IS-101 Reykjavik, Iceland. [Thorsteinsdottir, Unnur] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland. [Peters, Annette; Gieger, Christian; Rawal, Rajesh] Helmholtz Zentrum Munchen, Inst Epidemiol II, Neuherberg, Germany. [Peters, Annette; Gieger, Christian; Rawal, Rajesh] Munich Heart Alliance, Munich, Germany. [Thompson, John R.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England. [Erdmann, Jeanette] Med Univ Lubeck, Inst Integrat & Expt Genom, German Ctr Cardiovasc Res, Partner Site Hamburg Kiel Lubeck, D-23538 Lubeck, Germany. RP Schunkert, H (reprint author), Tech Univ Munich, Deutsch Herzzentrum Munchen, Lazarettstr 36, D-80636 Munich, Germany. RI Peters, Annette/A-6117-2011; Konig, Inke/A-4544-2009; Lieb, Wolfgang/C-1990-2012; Erdmann, Jeanette/P-7513-2014; OI Gieger, Christian/0000-0001-6986-9554; Ramachandran, Vasan/0000-0001-7357-5970; Erdmann, Jeanette/0000-0002-4486-6231; Assimes, Themistocles/0000-0003-2349-0009; Peters, Annette/0000-0001-6645-0985 FU EU-funded Integrated Projects Cardiogenics [LSHM-CT-2006-037593]; CVgenes@target; ENGAGE; BMBF-funded German National Genome Network (NGFN-Plus) Project Atherogenomics [FKZ: 01GS0831]; e:AtheroSysMed; German Excellence Center of Cardiovascular Research (DZHK); BMBF-funded (federal ministry for education and research) project GANI_MED [03IS2061A] FX Supported by the EU-funded Integrated Projects Cardiogenics (LSHM-CT-2006-037593), CVgenes@target and ENGAGE as well as the BMBF-funded German National Genome Network (NGFN-Plus) Project Atherogenomics (FKZ: 01GS0831) and e:AtheroSysMed, with participation in the German Excellence Center of Cardiovascular Research (DZHK), partner site Munich Heart Alliance and the Leducq consortium CADgenomics. WL has in part been supported by the BMBF-funded (federal ministry for education and research) project GANI_MED (03IS2061A). Information regarding the CARDIoGRAM members, acknowledgments, funding sources and disclosures are detailed in the online supplement. NR 49 TC 9 Z9 9 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD AUG PY 2015 VL 241 IS 2 BP 419 EP 426 DI 10.1016/j.atherosclerosis.2015.05.033 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CP7WT UT WOS:000360100700018 PM 26074316 ER PT J AU Ferencik, M Chatzizisis, YS AF Ferencik, Maros Chatzizisis, Yiannis S. TI Statins and the coronary plaque calcium "paradox": Insights from non-invasive and invasive imaging SO ATHEROSCLEROSIS LA English DT Editorial Material DE Atherosclerosis; Statins; Calcium ID LIPID-LOWERING THERAPY; COMPUTED-TOMOGRAPHY; PROGRESSION; ATHEROSCLEROSIS; CALCIFICATION; EVENTS; REGRESSION C1 [Ferencik, Maros] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Portland, OR 97201 USA. [Ferencik, Maros] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program,Med Sch, Boston, MA 02115 USA. [Chatzizisis, Yiannis S.] Harvard Univ, Brigham & Womens Hosp, Cardiovasc Div, Sch Med, Boston, MA 02115 USA. RP Chatzizisis, YS (reprint author), Harvard Univ, Brigham & Womens Hosp, Cardiovasc Div, Sch Med, 75 Francis St, Boston, MA 02115 USA. EM ychatzizisis@icloud.com NR 18 TC 1 Z9 2 U1 1 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD AUG PY 2015 VL 241 IS 2 BP 783 EP 785 DI 10.1016/j.atherosclerosis.2015.05.021 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CP7WT UT WOS:000360100700065 PM 26070488 ER PT J AU Charidimou, A Linn, J Vernooij, MW Opherk, C Akoudad, S Baron, JC Greenberg, SM Jager, HR Werring, DJ AF Charidimou, Andreas Linn, Jennifer Vernooij, Meike W. Opherk, Christian Akoudad, Saloua Baron, Jean-Claude Greenberg, Steven M. Jaeger, Hans Rolf Werring, David J. TI Cortical superficial siderosis: detection and clinical significance in cerebral amyloid angiopathy and related conditions SO BRAIN LA English DT Review DE cerebral amyloid angiopathy; small vessel disease; cortical superficial siderosis; magnetic resonance imaging; intracerebral haemorrhage ID CENTRAL-NERVOUS-SYSTEM; CONVEXITY SUBARACHNOID HEMORRHAGE; RECURRENT INTRACEREBRAL HEMORRHAGE; FOCAL NEUROLOGICAL EPISODES; SMALL VESSEL DISEASE; ATRIAL-FIBRILLATION; VASOCONSTRICTION SYNDROME; LOBAR HEMORRHAGE; INTRACRANIAL HEMORRHAGE; IMAGING ABNORMALITIES AB Cortical superficial siderosis (cSS) describes the deposition of blood-breakdown products over the cerebral hemisphere convexities. Often seen in cerebral amyloid angiopathy, cSS is associated with transient focal neurological episodes and increased intracerebral haemorrhage risk. Charidimou et al. review recent advances in the detection of cSS, plus mechanisms and clinical implications.Cortical superficial siderosis (cSS) describes the deposition of blood-breakdown products over the cerebral hemisphere convexities. Often seen in cerebral amyloid angiopathy, cSS is associated with transient focal neurological episodes and increased intracerebral haemorrhage risk. Charidimou et al. review recent advances in the detection of cSS, plus mechanisms and clinical implications.Cortical superficial siderosis describes a distinct pattern of blood-breakdown product deposition limited to cortical sulci over the convexities of the cerebral hemispheres, sparing the brainstem, cerebellum and spinal cord. Although cortical superficial siderosis has many possible causes, it is emerging as a key feature of cerebral amyloid angiopathy, a common and important age-related cerebral small vessel disorder leading to intracerebral haemorrhage and dementia. In cerebral amyloid angiopathy cohorts, cortical superficial siderosis is associated with characteristic clinical symptoms, including transient focal neurological episodes; preliminary data also suggest an association with a high risk of future intracerebral haemorrhage, with potential implications for antithrombotic treatment decisions. Thus, cortical superficial siderosis is of relevance to neurologists working in neurovascular, memory and epilepsy clinics, and neurovascular emergency services, emphasizing the need for appropriate blood-sensitive magnetic resonance sequences to be routinely acquired in these clinical settings. In this review we focus on recent developments in neuroimaging and detection, aetiology, prevalence, pathophysiology and clinical significance of cortical superficial siderosis, with a particular emphasis on cerebral amyloid angiopathy. We also highlight important areas for future investigation and propose standards for evaluating cortical superficial siderosis in research studies. C1 [Charidimou, Andreas; Jaeger, Hans Rolf; Werring, David J.] UCL Inst Neurol, Dept Brain Repair & Rehabil, Stroke Res Grp, London WC1N 3BG, England. [Charidimou, Andreas; Jaeger, Hans Rolf; Werring, David J.] Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England. [Charidimou, Andreas; Greenberg, Steven M.] Massachusetts Gen Hosp, Ctr Stroke Res, Boston, MA 02114 USA. [Linn, Jennifer] Univ Hosp Munich, Dept Neuroradiol, D-81377 Munich, Germany. [Vernooij, Meike W.; Akoudad, Saloua] Erasmus MC Univ Med Ctr, Dept Radiol, Rotterdam, Netherlands. [Vernooij, Meike W.; Akoudad, Saloua] Erasmus MC Univ Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Opherk, Christian] Univ Munich, Inst Stroke & Dementia Res, Munich, Germany. [Opherk, Christian] SLK Kliniken, Dept Neurol, Heilbronn, Germany. [Baron, Jean-Claude] Univ Paris 05, Sorbonne Paris Cite, UMR INSERM 894, Paris, France. [Jaeger, Hans Rolf] UCL Inst Neurol, Lysholm Dept Neuroradiol, London, England. [Jaeger, Hans Rolf] Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England. RP Werring, DJ (reprint author), Natl Hosp Neurol & Neurosurg, UCL Inst Neurol, Dept Brain Repair & Rehabil, Stroke Res Grp, Box 6,Queen Sq, London WC1N 3BG, England. EM d.werring@ucl.ac.uk RI Vernooij, Meike/E-4061-2016; OI Linn, Jennifer/0000-0003-0797-2761; baron, jean-claude/0000-0002-5264-2588 FU Greek State Scholarship Foundation; Stroke Association; British Heart Foundation; Samantha Dickson Brain Tumour Trust; Brain Research Trust; Department of Health's NIHR Biomedical Research Centres funding scheme FX Dr A Charidimou received research support from the Greek State Scholarship Foundation, the Stroke Association and the British Heart Foundation. Dr RJ Jager has received research support from the Samantha Dickson Brain Tumour Trust and the Brain Research Trust. Dr Werring receives research support from the Stroke Association and the British Heart Foundation. This work was partly undertaken at UCLH/UCL who received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme. NR 109 TC 24 Z9 25 U1 0 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD AUG 1 PY 2015 VL 138 BP 2126 EP 2139 DI 10.1093/brain/awv162 PN 8 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CQ4MJ UT WOS:000360578700013 PM 26115675 ER PT J AU Trotter, BB Robinson, ME Milberg, WP McGlinchey, RE Salat, DH AF Trotter, Benjamin B. Robinson, Meghan E. Milberg, William P. McGlinchey, Regina E. Salat, David H. TI Military blast exposure, ageing and white matter integrity SO BRAIN LA English DT Article DE CNS injury; imaging; concussion; traumatic brain injury; neuropathology; axon degeneration ID TRAUMATIC BRAIN-INJURY; AMYOTROPHIC-LATERAL-SCLEROSIS; PROFESSIONAL FOOTBALL PLAYERS; REDUCED CORTICAL THICKNESS; AGE-RELATED-CHANGES; DIFFUSION-TENSOR; ALZHEIMERS-DISEASE; FRACTIONAL ANISOTROPY; COGNITIVE IMPAIRMENT; HEAD-INJURY AB Mild traumatic brain injury, or concussion, is associated with a range of neural changes including altered white matter structure. There is emerging evidence that blast exposure-one of the most pervasive causes of casualties in the recent overseas conflicts in Iraq and Afghanistan-is accompanied by a range of neurobiological events that may result in pathological changes to brain structure and function that occur independently of overt concussion symptoms. The potential effects of brain injury due to blast exposure are of great concern as a history of mild traumatic brain injury has been identified as a risk factor for age-associated neurodegenerative disease. The present study used diffusion tensor imaging to investigate whether military-associated blast exposure influences the association between age and white matter tissue structure integrity in a large sample of veterans of the recent conflicts (n = 190 blast-exposed; 59 without exposure) between the ages of 19 and 62 years. Tract-based spatial statistics revealed a significant blast exposure x age interaction on diffusion parameters with blast-exposed individuals exhibiting a more rapid cross-sectional age trajectory towards reduced tissue integrity. Both distinct and overlapping voxel clusters demonstrating the interaction were observed among the examined diffusion contrast measures (e.g. fractional anisotropy and radial diffusivity). The regions showing the effect on fractional anisotropy included voxels both within and beyond the boundaries of the regions exhibiting a significant negative association between fractional anisotropy and age in the entire cohort. The regional effect was sensitive to the degree of blast exposure, suggesting a 'dose-response' relationship between the number of blast exposures and white matter integrity. Additionally, there was an age-independent negative association between fractional anisotropy and years since most severe blast exposure in a subset of the blast-exposed group, suggesting a specific influence of time since exposure on tissue structure, and this effect was also independent of post-traumatic stress symptoms. Overall, these data suggest that blast exposure may negatively affect brain-ageing trajectories at the microstructural tissue level. Additional work examining longitudinal changes in brain tissue integrity in individuals exposed to military blast forces will be an important future direction to the initial findings presented here. C1 [Trotter, Benjamin B.; Robinson, Meghan E.; Milberg, William P.; McGlinchey, Regina E.; Salat, David H.] VA Boston Healthcare Syst, Translat Res Ctr Traumat Brain Injury & Stress Di, RR&TBI Ctr Excellence, Boston, MA 02130 USA. [Trotter, Benjamin B.; Robinson, Meghan E.; Milberg, William P.; McGlinchey, Regina E.; Salat, David H.] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA 02130 USA. [Trotter, Benjamin B.; Robinson, Meghan E.; Salat, David H.] VA Boston Healthcare Syst, Neuroimaging Res Vet Ctr, Boston, MA 02130 USA. [Milberg, William P.; McGlinchey, Regina E.; Salat, David H.] Harvard Univ, Sch Med, Boston, MA USA. [Salat, David H.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Salat, DH (reprint author), VA Boston Healthcare Syst, 182 JP 150 S Huntington Ave, Boston, MA 02130 USA. EM salat@nmr.mgh.harvard.edu RI McGlinchey, Regina/R-1971-2016 FU Translational Research Center for TBI and Stress Disorders (TRACTS) VA Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence [B9254-C]; NIH [R01NR010827] FX This work was supported by funding from the Translational Research Center for TBI and Stress Disorders (TRACTS) VA Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence; Contract grant number: B9254-C (R.E.M. and W.P.M.) and NIH R01NR010827. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 102 TC 8 Z9 8 U1 5 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD AUG 1 PY 2015 VL 138 BP 2278 EP 2292 DI 10.1093/brain/awv139 PN 8 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CQ4MJ UT WOS:000360578700024 PM 26033970 ER PT J AU Florencia, M Veronica, D Liliana, O AF Florencia, Moreno Veronica, Dussel Liliana, Orellana CA ROHA Network TI Childhood cancer in Argentina: Survival 2000-2007 SO CANCER EPIDEMIOLOGY LA English DT Review DE Childhood cancer incidence; Epidemiology; Population registries; Survival ID INFORMATION-SYSTEM PROJECT; EARLY DEATHS; PEDIATRIC ONCOLOGY; INCOME COUNTRIES; CHILDREN; EUROPE; MORTALITY; LEUKEMIA; ADOLESCENTS; TRENDS AB Introduction: Information on the epidemiology of childhood cancer in Latin America is limited. The Argentinean Oncopaediatric Registry (ROHA) is a population-based registry active since 2000. This paper describes the 3-year survival experience of children diagnosed with cancer in Argentina during 2000-2007 by major morphological subgroup, age, sex, and geographical region of residence. Methods: Newly diagnosed paediatric cancer cases are registered in ROHA (estimated coverage is 93% of the country's cases). Three-year overall survival was estimated using Kaplan-Meier methods. Univariate Cox models were used to compare subgroup survival. Results: Between 2000 and 2007, a total of 10,181 new cancer diagnoses in children aged 0-14 years were reported to the registry. Three-year overall survival (95% CI) for all cancers was 61.7% (60.7; 62.7). Specific survival for the most frequent morphological types was: leukaemias 63.3% (61.6; 64.9), lymphomas and related neoplasms 75.3% (72.7; 77.7), brain neoplasms 46.3% (43.9; 48.7), soft-tissue sarcomas 52.3% (48.0; 56.5), neuroblastomas 49.6% (44.6; 54.3), renal tumours 76.7% (72.2; 80.6), and malignant bone tumours 47.2% (42.3; 51.9). Overall survival was associated with age but not sex and varied by geographical region. Compared to other regions, patients who resided in the capital city had a significantly higher survival: 69.6% (65.8; 73.0) versus 63.5% (59.4; 67.4) in Patagonia, 63.2% (61.9; 64.5) in the central region, 58.0% (54.2; 61.7) in Cuyo, 55.6% (52.5; 58.6) in the north-east, and 55.4% (52.4; 58.2) in the north-west (all P values < 0.005). Conclusions: Of children diagnosed with cancer in Argentina, 62% survived at least 3 years after diagnosis. Even though this figure is lower than that reported for more developed countries, survival patterns by diagnosis, age and sex were quite similar. Survival was lower in the two northern regions, which are areas with higher poverty levels. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Florencia, Moreno] Natl Canc Inst, Argentinean Oncopaediat Registry, Minister Hlth, Buenos Aires, DF, Argentina. [Veronica, Dussel] Inst Clin Effectiveness & Hlth Policy, Ctr Res & Implementat Palliat Care, Buenos Aires, DF, Argentina. [Veronica, Dussel] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Liliana, Orellana] Natl Canc Inst, Buenos Aires, DF, Argentina. [Liliana, Orellana] Deakin Univ, Biostat Unit, Fac Hlth, Burwood, Vic 3125, Australia. RP Florencia, M (reprint author), Natl Canc Inst, Argentinean Oncopaediat Registry ROHA, Ave Julio A Roca 781 10th Floor, Buenos Aires, DF, Argentina. EM roha@roha.org.ar; veronica_dussel@dfci.harvard.edu; l.orellana@deakin.edu.au RI Orellana, Liliana/I-5249-2013 OI Orellana, Liliana/0000-0003-3736-4337 FU Union for International Cancer Control FX This article was written as part of the workshop "Writing a scientific publication" organised by the International Agency for Research on Cancer and supported by the Union for International Cancer Control. The authors would like to give their special thanks to Melina Arnold, Esther de Vries and Monica Sierra for their constructive comments and warm encouragement. The authors specially thank the ROHA network and are particularly grateful for the extraordinary assistance given by Judith Goldman and Ines Kumcher. NR 35 TC 2 Z9 2 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1877-7821 EI 1877-783X J9 CANCER EPIDEMIOL JI Cancer Epidemiol. PD AUG PY 2015 VL 39 IS 4 BP 505 EP 510 DI 10.1016/j.canep.2015.04.010 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CP7BX UT WOS:000360043300003 ER PT J AU Hannan, EL Samadashvili, Z Jordan, D Sundt, TM Stamato, NJ Lahey, SJ Gold, JP Wechsler, A Ashraf, MH Ruiz, C Wilson, S Smith, CR AF Hannan, Edward L. Samadashvili, Zaza Jordan, Desmond Sundt, Thoralf M., III Stamato, Nicholas J. Lahey, Stephen J. Gold, Jeffrey P. Wechsler, Andrew Ashraf, Mohammed H. Ruiz, Carlos Wilson, Sean Smith, Craig R. TI Thirty-Day Readmissions After Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement in Patients With Severe Aortic Stenosis in New York State SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE aortic valve stenosis; heart failure; patient readmission; risk factors; transcatheter aortic valve replacement ID CLINICAL-OUTCOMES; PROPENSITY SCORE; RISK PATIENTS; TRIAL AB Background Several studies have compared short-term and medium-term mortality rates for patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR), but no studies have compared short-term readmission rates for the 2 procedures. Methods and Results New York's Cardiac Surgery Reporting System was used to propensity match 617 TAVI and 1981 SAVR patients using numerous patient risk factors contained in the registry. The 389 propensity-matched pairs were then used to analyze differences in readmission rates between the 2 groups. TAVI and SAVR readmission rates were also compared for patients with a history of congestive heart failure and for patients aged 80. Also, reasons for readmission for TAVI and SAVR patients were examined and compared. Readmission rates were not statistically different for all propensity-matched TAVI and SAVR patients (respective rates, 18.8% and 19.3%; P=0.86). After further adjustment using a logistic regression model, there was still no significant difference (adjusted odds ratio, 0.97; 95% confidence interval [0.68-1.39]). For patients aged 80, the 30-day readmission rates were 19.9% and 22.0% (P=0.59), and when further adjusted using the logistic regression model, adjusted odds ratio=0.89 (0.55-1.45). For patients with a history of congestive heart failure, the respective rates were 22.8% and 20.4% (P=0.56), and with further adjustment, adjusted odds ratio became 1.15 (0.72-1.82). Conclusions There are no statistically significant differences between TAVI and SAVR patients in short-term readmission rates. C1 [Hannan, Edward L.; Samadashvili, Zaza] SUNY Albany, Sch Publ Hlth, Albany, NY 12222 USA. [Jordan, Desmond] Columbia Presbyterian Med Ctr, Dept Anesthesiol, New York, NY 10032 USA. [Smith, Craig R.] Columbia Presbyterian Med Ctr, Dept Surg, New York, NY 10032 USA. [Sundt, Thoralf M., III] Massachusetts Gen Hosp, Ctr Heart, Boston, MA 02114 USA. [Sundt, Thoralf M., III] Massachusetts Gen Hosp, Inst Heart Vasc & Stroke, Boston, MA 02114 USA. [Stamato, Nicholas J.] Campbell Cty Mem Hosp, Dept Cardiol, Gillette, WY USA. [Lahey, Stephen J.] Univ Connecticut, Div Cardiothorac Surg, Storrs, CT USA. [Gold, Jeffrey P.] Univ Nebraska Med Ctr, Omaha, NE USA. [Wechsler, Andrew] Drexel Univ, Coll Med, Dept Cardiothorac Surg, Philadelphia, PA 19104 USA. [Ashraf, Mohammed H.] Kaleida Hlth, Dept Cardiothorac Surg, Buffalo, NY USA. [Ruiz, Carlos] Lenox Hill Hosp, Div Struct & Congenital Heart Dis, New York, NY 10021 USA. [Wilson, Sean] Valley Hosp, Dept Surg, Ridgewood, NJ USA. RP Hannan, EL (reprint author), SUNY Albany, Sch Publ Hlth, One Univ Pl, Rensselaer, NY 12144 USA. EM elh03@health.state.ny.us FU St. Jude Medical Center; Edwards Lifesciences FX Dr Sundt is a scientific advisor for Thrasos Innovation and the principal investigator (PI) for the Placement of Aortic Transcatheter Valve (PARTNER) trial (Edwards) and Pericardial Surgical Aortic Valve Replacement (Perigon) trial (Medtronic) at Massachusetts General Hospital. Dr Ruiz reports grant and speaker honoraria from St. Jude Medical Center. Dr Smith is the Surgical PI of the PARTNER trial, for which he receives reimbursement from the sponsor (Edwards Lifesciences) for travel and customary expenses related to trial management. The other authors report no conflicts. NR 28 TC 4 Z9 4 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-7640 EI 1941-7632 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD AUG PY 2015 VL 8 IS 8 AR e002744 DI 10.1161/CIRCINTERVENTIONS.115.002744 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CP9GH UT WOS:000360201300001 PM 26227347 ER PT J AU Gutierrez, JA Karwatowska-Prokopczuk, E Murphy, SA Belardinelli, L Farzaneh-Far, R Walker, G Morrow, DA Scirica, BM AF Gutierrez, Jorge A. Karwatowska-Prokopczuk, Ewa Murphy, Sabina A. Belardinelli, Luiz Farzaneh-Far, Ramin Walker, Gennyne Morrow, David A. Scirica, Benjamin M. TI Effects of Ranolazine in Patients With Chronic Angina in Patients With and Without Percutaneous Coronary Intervention for Acute Coronary Syndrome: Observations From the MERLIN-TIMI 36 Trial SO CLINICAL CARDIOLOGY LA English DT Article ID MYOCARDIAL-INFARCTION; REPERFUSION INJURY; ISCHEMIA; AMLODIPINE; EFFICACY; PECTORIS; UPDATE AB BackgroundRanolazine, a piperazine derivative with anti-ischemic effects, reduces the frequency of angina and improves exercise performance in patients with chronic angina. The effects of ranolazine in patients with established ischemic heart disease and chronic angina undergoing percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS) is not well described. We hypothesized that ranolazine would reduce ischemic events, regardless of revascularization. MethodsWe examined the 1-year incidence of recurrent cardiovascular (CV) events in the subgroup of patients with prior chronic angina (n=3565) enrolled in the randomized, double-blind, placebo-controlled Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-Elevation ACS (MERLIN)-Thrombolysis In Myocardial Infarction (TIMI) 36 trial who did or did not have a PCI within 30 days of the index event. ResultsRanolazine reduced the risk of recurrent ischemia following admission regardless of whether patients had (hazard ratio [HR], 0.69; 95% confidence interval [CI] 0.51-0.92] or did not have PCI (HR, 0.81; 95% CI, 0.66-0.99; P interaction=0.39). CV death, myocardial infarction, and recurrent ischemia were similarly lower with ranolazine in the PCI group (HR, 0.71; 95% CI, 0.55-0.91) vs the non-PCI group (HR, 0.91; 95% CI, 0.78-1.06; P interaction=0.10), with a nominally significant decrease in CV death (HR, 0.39; 95% CI, 0.16-0.93) in the PCI group vs no difference in the non-PCI group (HR, 1.19; 95% CI, 0.89-1.59; P interaction=0.02). ConclusionsIn patients with chronic angina, ranolazine reduced recurrent ischemic events, regardless of whether patients did or did not receive PCI within 30 days of a non-ST-segment ACS. C1 [Gutierrez, Jorge A.; Murphy, Sabina A.; Morrow, David A.; Scirica, Benjamin M.] Brigham & Womens Hosp, TIMI Study Grp, Cardiovasc Div, Dept Med, Boston, MA 02115 USA. [Gutierrez, Jorge A.; Murphy, Sabina A.; Morrow, David A.; Scirica, Benjamin M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Karwatowska-Prokopczuk, Ewa; Belardinelli, Luiz; Farzaneh-Far, Ramin] Gilead Sci Inc, Foster City, CA USA. RP Scirica, BM (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA. EM bscirica@partners.org FU Boehringer Ingelheim; TIMI Study Group; Brigham and Women's Hospital from AstraZeneca; Bristol-Myers Squibb; Daiichi-Sankyo; GlaxoSmithKline; Johnson and Johnson; Bayer Healthcare; Gilead; Eisai; Merck; Brigham and Women's Hospital from Accumetrics; Amgen; AstraZeneca; Beckman Coulter; CV Therapeutics; Daiichi Sankyo Co Ltd; Eli Lilly and Co; Integrated Therapeutics; Merck and Co; Nanosphere; Novartis Pharmaceuticals; Nuvelo; Ortho-Clinical Diagnostics; Pfizer; Roche Diagnostics; Sanofi-Aventis; Sanofi-Synthelabo; Siemens Medical Solutions; Singulex; Abbott Laboratories; Daiichi Sankyo; diaDexus; Instrumentation Laboratory; Konica Minolta; Novartis; TIMI Study; Arena; Boston Clinical Research Institute; Covance; Elsevier Practice Update Cardiology; Forest Pharmaceuticals; GE Healthcare; Lexicon; St. Jude's Medical; University of Calgary FX Dr. Gutierrez has received consulting fees from Boehringer Ingelheim. Ewa Karwatowska-Prokopczuk, Luiz Belardinelli, Ramin Farzaneh-Far, and Gennyne Walker are employees of Gilead Sciences, Inc. Sabina A. Murphy reports research grants via the TIMI Study Group and Brigham and Women's Hospital from AstraZeneca and Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Johnson and Johnson, Bayer Healthcare, Gilead, Eisai, and Merck. Dr. Morrow reports research grants via the TIMI Study Group and Brigham and Women's Hospital from Accumetrics, Amgen, AstraZeneca, Beckman Coulter, Bristol-Myers Squibb, CV Therapeutics, Daiichi Sankyo Co Ltd, Eli Lilly and Co, GlaxoSmithKline, Integrated Therapeutics, Merck and Co, Nanosphere, Novartis Pharmaceuticals, Nuvelo, Ortho-Clinical Diagnostics, Pfizer, Roche Diagnostics, Sanofi-Aventis, Sanofi-Synthelabo, Siemens Medical Solutions, and Singulex. Dr. Morrow has received consulting fees from Abbott Laboratories, Daiichi Sankyo, diaDexus, Gilead, Instrumentation Laboratory, Konica Minolta, Merck, and Novartis. Dr. Scirica reports research grants via the TIMI Study and Brigham and Women's Hospital from AstraZeneca and Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Johnson and Johnson, Bayer Healthcare, Gilead, Eisai, Merck, and has received consulting fees from Arena, AstraZeneca, Boehringer Ingelheim, Boston Clinical Research Institute, Bristol-Myers Squibb, Covance, Eisai, Elsevier Practice Update Cardiology, Forest Pharmaceuticals, GE Healthcare, Gilead, GlaxoSmithKline, Lexicon, St. Jude's Medical, University of Calgary. NR 19 TC 11 Z9 11 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 EI 1932-8737 J9 CLIN CARDIOL JI Clin. Cardiol. PD AUG PY 2015 VL 38 IS 8 BP 469 EP 475 DI 10.1002/clc.22425 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CP7RW UT WOS:000360086700004 PM 26059896 ER PT J AU Tirumani, H Rosenthal, MH Tirumani, SH Shinagare, AB Krajewski, KM Ramaiya, NH AF Tirumani, H. Rosenthal, M. H. Tirumani, S. H. Shinagare, A. B. Krajewski, K. M. Ramaiya, N. H. TI Imaging of uncommon esophageal malignancies SO DISEASES OF THE ESOPHAGUS LA English DT Review DE esophageal malignancy; gastrointestinal stromal tumor; lymphoma; melanoma; small-cell carcinoma ID SMALL-CELL CARCINOMA; GASTROINTESTINAL STROMAL TUMOR; HODGKINS-LYMPHOMA; MELANOMA; FEATURES; SARCOMA; CANCER; RADIOTHERAPY; LIPOSARCOMA; NEOPLASMS AB Malignant esophageal neoplasms other than squamous cell carcinoma and adenocarcinoma are uncommon and include endocrine tumors, lymphoid malignancies, melanoma, malignant stromal tumors, and secondary tumors (metastases). Imaging, though not diagnostic in many cases, helps in selecting the appropriate treatment strategy by determining the anatomic extent of the tumor and locoregional and distant spread. In this article, we provide a comprehensive review of the imaging features of these uncommon esophageal malignancies. C1 [Tirumani, H.; Rosenthal, M. H.; Tirumani, S. H.; Shinagare, A. B.; Krajewski, K. M.; Ramaiya, N. H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Imaging,Dana Farber Canc Inst, Boston, MA USA. [Rosenthal, M. H.; Tirumani, S. H.; Shinagare, A. B.; Krajewski, K. M.; Ramaiya, N. H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA USA. RP Tirumani, SH (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM stirumani@partners.org NR 45 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1120-8694 EI 1442-2050 J9 DIS ESOPHAGUS JI Dis. Esophagus PD AUG-SEP PY 2015 VL 28 IS 6 BP 552 EP 559 DI 10.1111/dote.12208 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CQ4NN UT WOS:000360581700008 PM 24635682 ER PT J AU Mimura, N Hideshima, T Anderson, KC AF Mimura, Naoya Hideshima, Tern Anderson, Kenneth C. TI Novel therapeutic strategies for multiple myeloma SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID UNFOLDED PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM STRESS; HISTONE DEACETYLASE INHIBITOR; CYTOTOXIC T-LYMPHOCYTES; NF-KAPPA-B; MARROW STROMAL CELLS; XBP1 MESSENGER-RNA; BONE-MARROW; ANTI-PD-1 ANTIBODY; SUPPRESSOR-CELLS AB Multiple myeloma (MM) is a plasma-cell malignancy which remains incurable despite the recent emergence of multiple novel agents. Importantly, recent genetic and molecular analyses have revealed the complexity and heterogeneity of this disease, highlighting the need for therapeutic strategies to eliminate all clones. Moreover, the bone marrow microenvironment, including stromal cells and immune cells, plays a central role in MM pathogenesis, promoting tumor cell growth, survival, and drug resistance. New classes of agents including proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, and histone deacetylase inhibitors have shown remarkable efficacy; however, novel therapeutic approaches are still urgently needed to further improve patient outcomes. In this review, we discuss the recent advances and future strategies to ultimately develop MM therapies with curative potential. Copyright (C) 2015 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. C1 [Mimura, Naoya] Chiba Univ Hosp, Dept Transfus Med & Cell Therapy, Chiba 2608677, Japan. [Hideshima, Tern; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02215 USA. RP Mimura, N (reprint author), Chiba Univ Hosp, Dept Transfus Med & Cell Therapy, 1-8-1 Chuo Ku, Chiba 2608677, Japan. EM naoyamimura@chiba-u.jp; kenneth_anderson@dfci.harvard.edu FU National Institutes of Health Specialized Programs of Research Excellence (SPORE) [P50100707, PO1-CA078378, RO1 CA050947] FX This work was supported by National Institutes of Health Specialized Programs of Research Excellence (SPORE) grants P50100707, PO1-CA078378, and RO1 CA050947. KC Anderson is an American Cancer Society Clinical Research Professor. NR 154 TC 16 Z9 17 U1 3 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X EI 1873-2399 J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 2015 VL 43 IS 8 BP 732 EP 741 DI 10.1016/j.exphem.2015.04.010 PG 10 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA CQ0XM UT WOS:000360321900013 PM 26118499 ER PT J AU Wolpin, BM AF Wolpin, Brian M. TI Pancreatic Cancer Preface SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 Harvard Univ, Sch Med, Ctr Gastrointestinal Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Wolpin, BM (reprint author), Harvard Univ, Sch Med, Ctr Gastrointestinal Oncol, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM bwolpin@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD AUG PY 2015 VL 29 IS 4 BP XIII EP XIV DI 10.1016/j.hoc.2015.06.002 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA CQ2FS UT WOS:000360416000001 PM 26226911 ER PT J AU Kim, TS Fernandez-del Castillo, C AF Kim, Teresa S. Fernandez-del Castillo, Carlos TI Diagnosis and Management of Pancreatic Cystic Neoplasms SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Pancreatic cyst; Intraductal papillary mucinous neoplasm (IPMN); Mucinous cystic neoplasm (MCN); Serous cystadenoma (SCA); Endoscopic ultrasound (EUS) ID PAPILLARY-MUCINOUS NEOPLASMS; INTERNATIONAL CONSENSUS GUIDELINES; SOLID-PSEUDOPAPILLARY TUMORS; LONG-TERM SURVIVAL; NEUROENDOCRINE TUMORS; FOLLOW-UP; ENDOSCOPIC-ULTRASOUND; ENDOCRINE NEOPLASMS; SEROUS-CYSTADENOMA; UPDATED EXPERIENCE AB Incidentally discovered pancreatic cystic lesions are increasingly common, affecting up to 10% to 15% of patients undergoing cross-sectional imaging. Although some pancreatic cystic neoplasms harbor invasive malignancy or the potential to progress over time, a majority are benign and can be observed safely. Accurate diagnosis is key to appropriate management. Diagnosis requires a multidisciplinary and multimodal approach. This review discusses each type of pancreatic cystic neoplasm and the current data on diagnosis and treatment. C1 [Kim, Teresa S.; Fernandez-del Castillo, Carlos] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Fernandez-del Castillo, C (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,WAC-460, Boston, MA 02114 USA. EM cfernandez@partners.org NR 78 TC 4 Z9 4 U1 2 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD AUG PY 2015 VL 29 IS 4 BP 655 EP + DI 10.1016/j.hoc.2015.04.002 PG 21 WC Oncology; Hematology SC Oncology; Hematology GA CQ2FS UT WOS:000360416000006 PM 26226903 ER PT J AU Rosenthal, MH Lee, A Jajoo, K AF Rosenthal, Michael H. Lee, Alexander Jajoo, Kunal TI Imaging and Endoscopic Approaches to Pancreatic Cancer SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Imaging; Endoscopy; Pancreatic adenocarcinoma; Cancer diagnosis; Cancer staging ID FINE-NEEDLE-ASPIRATION; MALIGNANT BILIARY STRICTURES; EXPANDING METAL STENTS; RETROGRADE CHOLANGIOPANCREATOGRAPHY; MULTIDETECTOR CT; ADVERSE EVENTS; BRUSH CYTOLOGY; CLINICAL-TRIAL; EUS; ULTRASOUND AB Imaging and endoscopy both play important and complementary roles in the initial diagnosis, staging, monitoring, and symptomatic management of pancreatic cancer. This article provides an overview of the uses of each of the diagnostic modalities, common imaging findings, alternative considerations, and areas of ongoing work in diagnostic imaging. This article also provides details of the uses of endoscopy for diagnosis, staging, and intervention throughout the course of a patient's care. These modalities each play important roles in the complex multidisciplinary care of patients with pancreatic cancer. C1 [Rosenthal, Michael H.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Rosenthal, Michael H.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Rosenthal, Michael H.; Lee, Alexander; Jajoo, Kunal] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Lee, Alexander; Jajoo, Kunal] Brigham & Womens Hosp, Dept Med, Div Gastroenterol, Boston, MA 02115 USA. RP Rosenthal, MH (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM Michael_Rosenthal@dfci.harvard.edu NR 59 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD AUG PY 2015 VL 29 IS 4 BP 675 EP + DI 10.1016/j.hoc.2015.04.008 PG 26 WC Oncology; Hematology SC Oncology; Hematology GA CQ2FS UT WOS:000360416000007 PM 26226904 ER PT J AU Clancy, TE AF Clancy, Thomas E. TI Surgery for Pancreatic Cancer SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Pancreatic cancer; Surgery; Pancreaticoduodenectomy; Whipple; Distal pancreatectomy ID PYLORUS-PRESERVING PANCREATICODUODENECTOMY; ANTEGRADE MODULAR PANCREATOSPLENECTOMY; RANDOMIZED-CONTROLLED-TRIAL; INTERNATIONAL STUDY-GROUP; LONG-TERM SURVIVAL; HOSPITAL VOLUME; DISTAL PANCREATECTOMY; DUCTAL ADENOCARCINOMA; STAGING LAPAROSCOPY; VASCULAR RESECTION AB Surgical resection remains the only potentially curative therapy for pancreatic cancer, despite a high rate of systemic recurrence. Because of local invasion or distant spread, a minority of patients presenting with pancreatic cancer are candidates for surgery. Although perioperative mortality is low in high-volume settings, pancreatic surgery remains associated with considerable morbidity. Minimally invasive and robotic surgical techniques are increasingly used for pancreatic resection, although not always applicable to all patients. Strategies to extend the benefits of margin-negative surgical resection to more patients include surgery with vascular resection and reconstruction for locally invasive tumors, and resection after neoadjuvant therapy. C1 [Clancy, Thomas E.] Brigham & Womens Hosp, Div Surg Oncol, Boston, MA 02115 USA. [Clancy, Thomas E.] Dana Farber Brigham & Womens Canc Ctr, Pancreas & Biliary Tumor Ctr, Boston, MA 02115 USA. [Clancy, Thomas E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Clancy, TE (reprint author), Brigham & Womens Hosp, Div Surg Oncol, 75 Francis St, Boston, MA 02115 USA. EM tclancy@partners.org NR 102 TC 6 Z9 6 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD AUG PY 2015 VL 29 IS 4 BP 701 EP + DI 10.1016/j.hoc.2015.04.001 PG 17 WC Oncology; Hematology SC Oncology; Hematology GA CQ2FS UT WOS:000360416000008 PM 26226905 ER PT J AU Rubinson, DA Wolpin, BM AF Rubinson, Douglas A. Wolpin, Brian M. TI Therapeutic Approaches for Metastatic Pancreatic Adenocarcinoma SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Pancreatic cancer; Metastatic disease; Gemcitabine; FOLFIRINOX; Nab-paclitaxel; Targeted therapy ID PHASE-III TRIAL; COOPERATIVE-ONCOLOGY-GROUP; GEMCITABINE PLUS PLACEBO; GROWTH-FACTOR RECEPTOR; COMPARING GEMCITABINE; 1ST-LINE TREATMENT; RANDOMIZED-TRIAL; DOUBLE-BLIND; DUCTAL ADENOCARCINOMA; CANCER AB Since the US Food and Drug Administration's approval of gemcitabine in 1996, numerous randomized trials have investigated treatment programs to further improve the quality of life and survival of patients with advanced pancreatic cancer. After little progress over the ensuing 15 years, 2 combination treatment programs recently conferred improved survival compared with gemcitabine monotherapy in patients with metastatic pancreatic cancer: FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan, oxaliplatin) and gemcitabine plus nab-paclitaxel. Importantly, our understanding of the biology of pancreatic cancer continues to grow. This improved biologic understanding holds great promise for integrating new targeted and immune-modifying therapies into current treatment programs. C1 [Rubinson, Douglas A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Rubinson, Douglas A.; Wolpin, Brian M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Wolpin, Brian M.] Dana Farber Canc Inst, Pancreas & Biliary Tumor Ctr, Dept Med Oncol, Boston, MA 02215 USA. RP Wolpin, BM (reprint author), Harvard Univ, Sch Med, 25 Shattuck St, Boston, MA 02115 USA. EM bwolpin@partners.org NR 59 TC 4 Z9 6 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD AUG PY 2015 VL 29 IS 4 BP 761 EP + DI 10.1016/j.hoc.2015.04.012 PG 17 WC Oncology; Hematology SC Oncology; Hematology GA CQ2FS UT WOS:000360416000012 PM 26226909 ER PT J AU Narayanaswami, P Gronseth, G Dubinsky, R Penfold-Murray, R Cox, J Bever, C Martins, Y Rheaume, C Shouse, D Getchius, TSD AF Narayanaswami, Pushpa Gronseth, Gary Dubinsky, Richard Penfold-Murray, Rebecca Cox, Julie Bever, Christopher, Jr. Martins, Yolanda Rheaume, Carol Shouse, Denise Getchius, Thomas S. D. TI The Impact of Social Media on Dissemination and Implementation of Clinical Practice Guidelines: A Longitudinal Observational Study SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE information dissemination; social media; multiple sclerosis; complementary medicine; medicine; complementary; therapy, complementary; alternative medicine; alternative therapies; clinical practice guidelines; dissemination and implementation ID MULTIPLE-SCLEROSIS PATIENTS; ALTERNATIVE MEDICINE; COMPLEMENTARY; INFORMATION; YOUTUBE; INTERVENTION; PREVENTION; INTERNET; QUALITY; TWITTER AB Background: Evidence-based clinical practice guidelines (CPGs) are statements that provide recommendations to optimize patient care for a specific clinical problem or question. Merely reading a guideline rarely leads to implementation of recommendations. The American Academy of Neurology (AAN) has a formal process of guideline development and dissemination. The last few years have seen a burgeoning of social media such as Facebook, Twitter, and LinkedIn, and newer methods of dissemination such as podcasts and webinars. The role of these media in guideline dissemination has not been studied. Systematic evaluation of dissemination methods and comparison of the effectiveness of newer methods with traditional methods is not available. It is also not known whether specific dissemination methods may be more effectively targeted to specific audiences. Objective: Our aim was to (1) develop an innovative dissemination strategy by adding social media-based dissemination methods to traditional methods for the AAN clinical practice guidelines "Complementary and alternative medicine in multiple sclerosis" ("CAM in MS") and (2) evaluate whether the addition of social media outreach improves awareness of the CPG and knowledge of CPG recommendations, and affects implementation of those recommendations. Methods: Outcomes were measured by four surveys in each of the two target populations: patients and physicians/clinicians ("physicians"). The primary outcome was the difference in participants' intent to discuss use of complementary and alternative medicine (CAM) with their physicians or patients, respectively, after novel dissemination, as compared with that after traditional dissemination. Secondary outcomes were changes in awareness of the CPG, knowledge of CPG content, and behavior regarding CAM use in multiple sclerosis (MS). Results: Response rates were 25.08% (622/2480) for physicians and 43.5% (348/800) for patients. Awareness of the CPG increased after traditional dissemination (absolute difference, 95% confidence interval: physicians 36%, 95% CI 25-46, and patients 10%, 95% CI 1-11) but did not increase further after novel dissemination (physicians 0%, 95% CI -11 to 11, and patients -4%, 95% CI -6 to 14). Intent to discuss CAM also increased after traditional dissemination but did not change after novel dissemination (traditional: physicians 12%, 95% CI 2-22, and patients 19%, 95% CI 3-33; novel: physicians 11%, 95% CI -1 to 21, and patients -8%, 95% CI -22 to 8). Knowledge of CPG recommendations and behavior regarding CAM use in MS did not change after either traditional dissemination or novel dissemination. Conclusions: Social media-based dissemination methods did not confer additional benefit over print-, email-, and Internet-based methods in increasing CPG awareness and changing intent in physicians or patients. Research on audience selection, message formatting, and message delivery is required to utilize Web 2.0 technologies optimally for dissemination. C1 [Narayanaswami, Pushpa] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Gronseth, Gary; Dubinsky, Richard] Univ Kansas, Sch Med, Dept Neurol, Kansas City, KS USA. [Penfold-Murray, Rebecca; Cox, Julie; Rheaume, Carol; Shouse, Denise; Getchius, Thomas S. D.] Amer Acad Neurol, Minneapolis, MN USA. [Bever, Christopher, Jr.] Univ Maryland, Sch Med, Dept Neurol, VA Maryland Hlth Care Syst MS Ctr Excellence, Baltimore, MD 21201 USA. [Martins, Yolanda] Harvard Univ, Sch Med, Dana Farber Canc Inst, Survey & Data Management Core, Boston, MA 02215 USA. RP Narayanaswami, P (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Neurol TCC 8,330 Brookline Ave, Boston, MA 02215 USA. EM pnarayan@bidmc.harvard.edu OI Rheaume, Carol/0000-0002-9224-1359; Bever, Christopher/0000-0001-7838-3222; Narayanaswami, Pushpa/0000-0002-9412-7349 FU AHRQ [1R18HS022004-01]; Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Research Resources); Harvard University and its affiliated academic health care centers; National Center for Advancing Translational Sciences, National Institutes of Health Award [UL1 TR001102] FX This study was funded by AHRQ Grant Number 1R18HS022004-01. The work was conducted with support from Harvard Catalyst/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 UL1 TR001102), and financial contributions from Harvard University and its affiliated academic health care centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, or the National Institutes of Health. NR 44 TC 5 Z9 5 U1 1 U2 8 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 2015 VL 17 IS 8 AR e193 DI 10.2196/jmir.4414 PG 12 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA CQ0SD UT WOS:000360306300002 PM 26272267 ER PT J AU Wang, MP Chu, JTW Viswanath, K Wan, A Lam, TH Chan, SS AF Wang, Man Ping Chu, Joanna T. W. Viswanath, Kasisomayajula Wan, Alice Lam, Tai Hing Chan, Sophia S. TI Using Information and Communication Technologies for Family Communication and Its Association With Family Well-Being in Hong Kong: FAMILY Project SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE information and communication technologies; family well-being; family communication; Chinese ID INTERNET; PERSPECTIVES; HAPPINESS; HARMONY; HEALTH; IMPACT; MEDIA; MODEL AB Background: Family communication is central to the family and its functioning. It is a mutual process in which family members create, share, and regulate meaning. Advancement and proliferation of information and communication technologies (ICTs) continues to change methods of family communication. However, little is known about the use of different methods for family communication and the influence on family well-being. Objective: We investigated the sociodemographic factors associated with different methods of family communication and how they are associated with perceived family harmony, happiness, and health (3Hs) among Chinese adults in Hong Kong. Methods: Data came from a territory-wide probability-based telephone survey using the Family and Health Information Trend survey (FHInTs). Frequency of family communication using different methods (ie, face-to-face, phone, instant messaging [ IM], social media sites, and email) were recoded and classified as frequent (always/sometimes) and nonfrequent (seldom/never) use. Family well-being was measured using 3 questions of perceived family harmony, happiness, and health with higher scores indicating better family well-being. Adjusted odds ratios for family communication methods by sociodemographic characteristics and adjusted beta coefficients for family well-being by communication methods were calculated. Results: A total of 1502 adults were surveyed. Face-to-face (94.85%, 1408/1484) was the most frequent means of communication followed by phone (78.08%, 796/1484), IM (53.64%, 796/1484), social media sites (17.60%, 261/1484), and email (13.39%, 198/1484). Younger age was associated with the use of phone, IM, and social media sites for family communication. Higher educational attainment was associated with more frequent use of all modes of communication, whereas higher family income was only significantly associated with more frequent use of IM and email (P=.001). Face-to-face (beta 0.65, 95% CI 0.33-0.97) and phone use (beta 0.20, 95% CI 0.02-0.38) for family communication were associated with significantly higher levels of perceived family well-being. Conclusions: Socioeconomic disparities in using these information and communication technologies (ICT) methods for family communication were observed. Although traditional methods remain as the main platform for family communication and were associated with better family well-being, a notable proportion of respondents are using new ICT methods, which were not associated with perceived family well-being. Because ICTs will continue to diversify modes of family communication, more research is needed to understand the impact of ICTs on family communication and well-being. C1 [Wang, Man Ping; Chan, Sophia S.] Univ Hong Kong, Sch Nursing, Hong Kong, Hong Kong, Peoples R China. [Chu, Joanna T. W.; Wan, Alice; Lam, Tai Hing] Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China. [Viswanath, Kasisomayajula] Harvard TH Chan Sch Publ Hlth, Ctr Community Based Res, Dana Farber Canc Inst, Dept Social & Behav Sci, Cambridge, MA USA. RP Lam, TH (reprint author), Univ Hong Kong, Sch Publ Hlth, 21 Sassoon Rd, Pokfulam, Hong Kong, Peoples R China. EM hrmrlth@hku.hk OI Chu, Joanna Ting Wai/0000-0002-5900-8141 FU Hong Kong Jockey Club Charities Trust FX The project was funded by the Hong Kong Jockey Club Charities Trust. We would like to thank the participants who participated in the telephone surveys and Public Opinion Programme (HKU) for conducting the surveys. NR 36 TC 1 Z9 1 U1 4 U2 28 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 2015 VL 17 IS 8 AR e207 DI 10.2196/jmir.4722 PG 10 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA CQ0SG UT WOS:000360306600010 PM 26303434 ER PT J AU Peterson, R AF Peterson, R. TI Optovins convert endogenous TRPA1 channels into photoreceptors SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 25th Biennial Meeting of the International-Society-for-Neurochemistry Jointly with the 13th Meeting of the Asian-Pacific-Society-for-Neurochemistry in Conjunction with the 35th Meeting of the Australasian-Neuroscience-Society CY AUG 23-27, 2015 CL Cairns, AUSTRALIA SP Int Soc Neurochemistry, Asian Pacific Soc Neurochemistry, Australasian Neuroscience Soc C1 [Peterson, R.] Harvard Univ, Sch Med, Syst Biol, Charlestown, MA USA. [Peterson, R.] Massachusetts Gen Hosp, Med, Charlestown, MA USA. [Peterson, R.] Broad Inst, Chem Biol, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2015 VL 134 SU 1 SI SI MA S29-02 BP 62 EP 62 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA CP9IA UT WOS:000360206300122 ER PT J AU Wu, L Ramirez, S Andrews, A Wu, J Lo, E Lok, J AF Wu, L. Ramirez, S. Andrews, A. Wu, J. Lo, E. Lok, J. TI Protective role of neuregulin 1 in inflammatory cytokine induced endothelial barrier hyperpermeability SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 25th Biennial Meeting of the International-Society-for-Neurochemistry Jointly with the 13th Meeting of the Asian-Pacific-Society-for-Neurochemistry in Conjunction with the 35th Meeting of the Australasian-Neuroscience-Society CY AUG 23-27, 2015 CL Cairns, AUSTRALIA SP Int Soc Neurochemistry, Asian Pacific Soc Neurochemistry, Australasian Neuroscience Soc C1 [Wu, L.; Lo, E.; Lok, J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Radiol, Charlestown, MA USA. [Wu, L.; Wu, J.] Jilin Univ, Hosp 1, Neurol, Changchun 130023, Peoples R China. [Ramirez, S.; Andrews, A.] Temple Univ, Sch Med Pathol & Lab Med, Philadelphia, PA 19122 USA. [Lok, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2015 VL 134 SU 1 SI SI MA MTU13-20 BP 227 EP 227 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA CP9IA UT WOS:000360206300559 ER PT J AU Chen, YF Masiakos, PT Gaz, RD Hodin, RA Parangi, S Randolph, GW Sadow, PM Stephen, AE AF Chen, Yufei Masiakos, Peter T. Gaz, Randall D. Hodin, Richard A. Parangi, Sareh Randolph, Gregory W. Sadow, Peter M. Stephen, Antonia E. TI Pediatric thyroidectomy in a high volume thyroid surgery center: Risk factors for postoperative hypocalcemia SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE Endocrine; Thyroidectomy; Hypocalcemia; Pediatric ID VITAMIN-D DEFICIENCY; GRAVES-DISEASE; MORBIDITY; OUTCOMES; INSTITUTION; CARCINOMA; CHILDREN; CANCER; TRENDS AB Introduction: Hypocalcemia is a common complication following thyroid surgery. We seek to report on our experience in pediatric thyroidectomy in a high volume thyroid surgery center and accurately assess the incidence of postoperative hypocalcemia. Materials and methods: A retrospective review of patients aged 18 and younger who underwent thyroid surgery between 1992 and 2013. The primary endpoints were the occurrence of postoperative hypocalcemia as by defined as a nadir calcium <8.0 mg/dL and being discharged on oral calcium supplementation, need for intravenous calcium and the occurrence of permanent hypoparathyroidism. Results: 171 patients who underwent 186 thyroid operations were analyzed. The average age was 15.4 years with 82.3% female. The most common indications for surgery were nodular disease (74.7%) and hyperthyroidism (12.4%). 24 patients (12.9%) experienced postoperative hypocalcemia with 13 (7.0%) requiring intravenous calcium infusion. One patient (0.9%) experienced permanent hypoparathyroidism. Risk factors for postoperative hypocalcemia included total thyroidectomy (OR 7.39, p < 0.01), central and bilateral lateral neck dissection (OR 22.26, p = 0.01), Graves' disease (OR 3.99, p = 0.02), and malignancy (OR 2.96, p = 0.03). Conclusions: Pediatric patients who undergo total thyroidectomy for underlying malignancy or Graves' disease and those who have more extensive nodal dissections are at increased risk of developing this postoperative hypocalcemia. These patients may benefit from more vigilant preoperative preparation and postoperative calcium and vitamin D supplementation. (C) 2015 Elsevier Inc. All rights reserved. C1 [Chen, Yufei; Masiakos, Peter T.; Gaz, Randall D.; Hodin, Richard A.; Parangi, Sareh; Randolph, Gregory W.; Sadow, Peter M.; Stephen, Antonia E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Randolph, Gregory W.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Chen, YF (reprint author), GRB-425,55 Fruit St, Boston, MA 02114 USA. EM ychen49@partners.org; pmasiakos@partners.org; gaz.randall@mgh.harvard.edu; rhodin@mgh.harvard.edu; sparangi@mgh.harvard.edu; gwrandolph@mgh.harvard.edu; psadow@partners.org; astephen@partners.org NR 25 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 0022-3468 EI 1531-5037 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD AUG PY 2015 VL 50 IS 8 BP 1316 EP 1319 DI 10.1016/j.jpedsurg.2014.10.056 PG 4 WC Pediatrics; Surgery SC Pediatrics; Surgery GA CP8DF UT WOS:000360121000014 PM 25783304 ER PT J AU Hunt, LJ Covinsky, KE Yaffe, K Stephens, CE Miao, YH Boscardin, WJ Smith, AK AF Hunt, Lauren J. Covinsky, Kenneth E. Yaffe, Kristine Stephens, Caroline E. Miao, Yinghui Boscardin, W. John Smith, Alex K. TI Pain in Community-Dwelling Older Adults with Dementia: Results from the National Health and Aging Trends Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE NHATS; community-dwelling; dementia; pain ID NURSING-HOME RESIDENTS; SELF-REPORTED PAIN; COGNITIVE IMPAIRMENT; UNITED-STATES; ALZHEIMERS-DISEASE; ASSESSMENT SCALES; CAREGIVER REPORT; PREVALENCE; PATIENT; DEPRESSION AB ObjectivesTo report prevalence, correlates, and medication management of pain in community-dwelling older adults with dementia. DesignCross-sectional. SettingIn-person interviews with self- or proxy respondents living in private residences or non-nursing home residential care settings. ParticipantsNationally representative sample of community-dwelling Medicare beneficiaries aged 65 and older enrolled in the National Health and Aging Trends Study 2011 wave. MeasurementsDementia status was determined using a modified previously validated algorithm. Participants were asked whether they had had bothersome and activity-limiting pain over the past month. A multivariable Poisson regression model was used to determine the relationship between bothersome pain and sociodemographic and clinical characteristics. ResultsOf the 7,609 participants with complete data on cognitive function, 802 had dementia (67.2% aged 80, 65.0% female, 67.9% white, 49.7% proxy response, 32.0% lived alone, 18.8% lived in residential care); 670 (63.5%) participants with dementia experienced bothersome pain, and 347 (43.3%) had pain that limited activities. These rates were significantly higher than in a propensity score-matched cohort without dementia (54.5% bothersome pain, P<.001, 27.2% pain that limited activity, P<.001). Proxies reported slightly higher rates of pain than self-respondents, but differences were statistically significant only for activity-limiting pain (46.6% proxy vs 40.1% self, P=.03). Correlates of bothersome pain included arthritis, heart and lung disease, less than high school education, activity of daily living disability, depressive and anxiety symptoms, and low energy. Of those reporting pain, 30.3% stated that they rarely or never took any medications for pain. ConclusionCommunity-living older adults with dementia are at high risk of having pain. Creative interventions and programs are needed to manage pain adequately in this vulnerable population. C1 [Hunt, Lauren J.] Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA 94143 USA. [Covinsky, Kenneth E.; Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Covinsky, Kenneth E.; Yaffe, Kristine; Smith, Alex K.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Stephens, Caroline E.] Univ Calif San Francisco, Dept Community Hlth Syst, San Francisco, CA 94143 USA. [Miao, Yinghui; Boscardin, W. John; Smith, Alex K.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Hunt, LJ (reprint author), Univ Calif San Francisco, Dept Physiol Nursing, 2 Koret Way,N-319X,UCSF Box 0602, San Francisco, CA 94143 USA. EM Lauren.Hunt@ucsf.edu FU National Institute of Nursing Research [T32-NR07088]; National Institute on Aging (NIA) [1K23 AG040772]; NIA [1 K24 AG041180, 2 K24 AG031155]; Clinical and Translational Sciences Institute Career Development Award [8 KL2 TR000143-08]; National Institute on Aging [U01AG032947]; Johns Hopkins Bloomberg School of Public Health FX LJH is supported by Grant T32-NR07088 from the National Institute of Nursing Research. AKS is supported by Paul Beeson Career Development Award in Aging 1K23 AG040772 from the National Institute on Aging (NIA). KEC is supported by Mentoring Award 1 K24 AG041180 from the NIA. KY is supported by Mentoring Award 2 K24 AG031155 from the NIA. CES is supported by Clinical and Translational Sciences Institute Career Development Award 8 KL2 TR000143-08. NHATS is sponsored by National Institute on Aging Grant U01AG032947 through a cooperative agreement with the Johns Hopkins Bloomberg School of Public Health. NR 50 TC 4 Z9 4 U1 1 U2 12 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 2015 VL 63 IS 8 BP 1503 EP 1511 DI 10.1111/jgs.13536 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CP9IG UT WOS:000360207000002 PM 26200445 ER PT J AU Sheffrin, M Miao, YH Boscardin, WJ Steinman, MA AF Sheffrin, Meera Miao, Yinghui Boscardin, W. John Steinman, Michael A. TI Weight Loss Associated with Cholinesterase Inhibitors in Individuals with Dementia in a National Healthcare System SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE cholinesterase inhibitors; dementia; weight loss ID PROBABLE VASCULAR DEMENTIA; PLACEBO-CONTROLLED TRIAL; ALZHEIMERS-DISEASE; DOUBLE-BLIND; LEWY BODIES; PARKINSONS-DISEASE; RANDOMIZED-TRIAL; DONEPEZIL; EFFICACY; TOLERABILITY AB ObjectivesTo determine whether initiation of cholinesterase inhibitors is associated with significant weight loss in a real-word clinical setting. DesignRetrospective cohort study from 2007 to 2010 comparing weight loss in individuals with dementia newly prescribed cholinesterase inhibitors and those newly prescribed other chronic medications. SettingNational Veterans Affairs data. ParticipantsIndividuals aged 65 and older with a diagnosis of dementia who received a new prescription for a cholinesterase inhibitor or other new chronic medication. MeasurementsThe primary outcome was time to 10-pound weight loss over 12months. Propensity score matching was used to control for the likelihood of receiving a cholinesterase inhibitor based on baseline characteristics. Data were analyzed in a priori defined subgroups according to age, comorbid burden, and initial weight. ResultsOf 6,504 individuals that met study criteria, 1,188 started on cholinesterase inhibitors were matched to 2,189 started on other medications. The propensity-matched cohorts were well balanced on baseline covariates. Participants initiated on cholinesterase inhibitors had a higher risk of weight loss than matched controls at 12months (hazard ratio=1.23, 95% confidence interval (CI) =1.07-1.41). At 12months, 29.3% of participants taking cholinesterase inhibitors had experienced weight loss, compared with 22.8% of nonusers, corresponding to a number needed to harm of 21.2 (95% CI=12.5-71.4) over 1year. There were no significant differences in the risk of weight loss within subgroups. ConclusionThese results are consistent with the available data from randomized controlled trials. Clinicians should consider the risk of weight loss when prescribing cholinesterase inhibitors. C1 [Sheffrin, Meera; Miao, Yinghui; Boscardin, W. John; Steinman, Michael A.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Sheffrin, Meera; Miao, Yinghui; Boscardin, W. John; Steinman, Michael A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Boscardin, W. John] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Sheffrin, M (reprint author), San Francisco VA Med Ctr, Div Geriatr, 4150 Clement St,Box 181-G, San Francisco, CA 94121 USA. EM meera.sheffrin@ucsf.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development, VA Information Resource Center; Centers for Medicare and Medicaid Services data [SDR 02-237, 98-004] FX The Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development, VA Information Resource Center provide support for VA and Centers for Medicare and Medicaid Services data (Project Numbers SDR 02-237 and 98-004). NR 32 TC 5 Z9 5 U1 1 U2 5 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 2015 VL 63 IS 8 BP 1512 EP 1518 DI 10.1111/jgs.13511 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CP9IG UT WOS:000360207000003 PM 26234945 ER PT J AU Lund, BC Carrel, M Gellad, WF Chrischilles, EA Kaboli, PJ AF Lund, Brian C. Carrel, Margaret Gellad, Walid F. Chrischilles, Elizabeth A. Kaboli, Peter J. TI Incidence- Versus Prevalence-Based Measures of Inappropriate Prescribing in the Veterans Health Administration SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE medication safety; quality of care; pharmacotherapy; pharmacoepidemiology ID BEERS CRITERIA; MEDICATION USE; QUALITY; CARE; IMPACT; ELDERS AB ObjectivesTo describe variations in potentially inappropriate prescribing (PIP) and characterize the extent to which switching to an incidence-based indicator would affect health system quality rankings. DesignObservational study. SettingVeterans Health Administration in 2011. ParticipantsOlder adults receiving outpatient primary care. MeasurementsPIP was defined according to the National Committee for Quality Assurance High-Risk Medications in the Elderly list. Ranks were separately assigned for prevalent and incident PIP at the regional, network, and healthcare system levels. ResultsNational PIP prevalence was 12.3% (167,766/1,360,251), and incidence was 5.8% (78,604/1,360,251). PIP prevalence ranged from 3.5% to 33.1% across healthcare systems (interquartile range (IQR)=9.2-15.5%). PIP incidence ranged from 1.2% to 14.9% (IQR=4.1-7.2%). Rank order in PIP prevalence and incidence was correlated (Spearman correlation; =0.934, P<.001), although substantial changes in ranks were seen for some healthcare systems, with seven of 139 (5.0%) systems shifting more than 30 rank positions and 21 (15.1%) systems shifting 16 to 30 positions. ConclusionPrevalence- and incidence-based indicators of prescribing quality were strongly correlated. Transitioning to incidence-based indicators would not produce an initial disruption in quality rankings for most healthcare systems and might yield more-salient measures for tracking healthcare quality. C1 [Lund, Brian C.; Carrel, Margaret] Iowa City Vet Affairs Hlth Care Syst, Ctr Comprehens Access & Delivery Res & Evaluat, Iowa City, IA USA. [Lund, Brian C.; Chrischilles, Elizabeth A.] Univ Iowa, Dept Epidemiol, Coll Publ Hlth, Iowa City, IA USA. [Carrel, Margaret] Univ Iowa, Coll Med, Dept Geog & Sustainabil Sci, Iowa City, IA USA. [Gellad, Walid F.] Vet Affairs Pittsburgh Hlth Care Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Gellad, Walid F.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. [Kaboli, Peter J.] Univ Iowa, Div Gen Internal Med, Coll Med, Iowa City, IA USA. RP Lund, BC (reprint author), VA Iowa City Hlth Care Syst, Mailstop 152,601 Hwy 6 West, Iowa City, IA 52246 USA. EM Brian.Lund@va.gov FU Health Services Research and Development Service, Department of Veterans Affairs [CDA 10-017, CIN 13-412, CDA 09-207] FX This study was supported by supported by the Health Services Research and Development Service, Department of Veterans Affairs (Dr. Lund, CDA 10-017 and CIN 13-412; Dr. Gellad, CDA 09-207). NR 28 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 2015 VL 63 IS 8 BP 1601 EP 1607 DI 10.1111/jgs.13560 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CP9IG UT WOS:000360207000014 PM 26200069 ER PT J AU Song, Y Dzierzewski, JM Fung, CH Rodriguez, JC Jouldjian, S Mitchell, MN Josephson, KR Alessi, CA Martin, JL AF Song, Yeonsu Dzierzewski, Joseph M. Fung, Constance H. Rodriguez, Juan C. Jouldjian, Stella Mitchell, Michael N. Josephson, Karen R. Alessi, Cathy A. Martin, Jennifer L. TI Association Between Sleep and Physical Function in Older Veterans in an Adult Day Healthcare Program SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE adult day health care; elderly adults; physical function; sleep; veterans ID ASSISTED LIVING FACILITIES; QUALITY-OF-LIFE; POOR SLEEP; ACTIVATION; DEPRESSION; DEMENTIA; VALIDITY; DECLINE; WOMEN; INDEX AB ObjectivesTo examine whether sleep disturbance is associated with poor physical function in older veterans in an adult day healthcare (ADHC) program. DesignCross-sectional. SettingOne ADHC program in a Veterans Affairs Ambulatory Care Center. ParticipantsOlder veterans (N=50) enrolled in a randomized controlled trial of a sleep intervention program who had complete baseline data. MeasurementsInformation on participant characteristics (e.g., age, depression, relationship to caregiver, pain, comorbidity) was collected using appropriate questionnaires. Physical function was measured using activity of daily living (ADL) and instrumental ADL (IADL) total scores from the Older Americans Resources and Services Multidimensional Functional Assessment Questionnaire. Sleep was assessed subjectively (Pittsburgh Sleep Quality Index, Insomnia Severity Index) and objectively (wrist actigraphy). ResultsParticipants required substantial assistance with ADLs and IADLs. A regression model showed that participant characteristics (marital status, use of sleep medication, comorbidity, posttraumatic stress disorder) and living arrangement (living with a spouse or others) were significantly associated with poor physical function. Poorer objective sleep (total sleep time, total numbers of awakenings, total wake time) was significantly associated with poor physical function, accounting for a significant proportion of the variance other than participant characteristics. ConclusionObjective measures of nighttime sleep disturbance were associated with poor physical function in older veterans in an ADHC program. Further research is needed to determine whether interventions to improve sleep will delay functional decline in this vulnerable population. C1 [Song, Yeonsu; Dzierzewski, Joseph M.; Fung, Constance H.; Rodriguez, Juan C.; Jouldjian, Stella; Mitchell, Michael N.; Josephson, Karen R.; Alessi, Cathy A.; Martin, Jennifer L.] Vet Affairs Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. [Dzierzewski, Joseph M.; Fung, Constance H.; Rodriguez, Juan C.; Alessi, Cathy A.; Martin, Jennifer L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Rodriguez, Juan C.] Pontificia Univ Catolica Chile, Dept Med, Santiago, Chile. RP Martin, JL (reprint author), VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr 11E, 16111 Plummer St, North Hills, CA 91343 USA. EM Jennifer.Martin@va.gov FU VA Rehabilitation Research and Development Service Merit Review Project [1RX000135-01]; VA Advanced Geriatrics Fellowship Program; VA Greater Los Angeles Healthcare System Geriatric Research, Education and Clinical Center; University of California at Los Angeles (UCLA) Claude Pepper Older Americans Independence Center [5P30AG028748]; National Center for Advancing Translational Sciences UCLA Clinical and Translational Science Institute [UL1TR000124]; National Institute on Aging, National Institutes of Health [K23AG045937] FX This study was supported by the VA Rehabilitation Research and Development Service Merit Review Project 1RX000135-01 (PI: Martin), VA Advanced Geriatrics Fellowship Program, and VA Greater Los Angeles Healthcare System Geriatric Research, Education and Clinical Center. Research reported in this publication was also supported by the University of California at Los Angeles (UCLA) Claude Pepper Older Americans Independence Center (5P30AG028748, PI: Dzierzewski), National Center for Advancing Translational Sciences UCLA Clinical and Translational Science Institute (UL1TR000124, PI: Dzierzewski), and National Institute on Aging, National Institutes of Health (K23AG045937, PI: Fung). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs, National Institute of Health, or the U.S. government. NR 29 TC 3 Z9 3 U1 4 U2 10 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 2015 VL 63 IS 8 BP 1622 EP 1627 DI 10.1111/jgs.13527 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CP9IG UT WOS:000360207000017 PM 26200520 ER PT J AU Troen, BR Ouslander, JG Yoshikawa, T AF Troen, Bruce R. Ouslander, Joseph G. Yoshikawa, Thomas TI Statement of Principle SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material C1 [Troen, Bruce R.] SUNY Buffalo, Dept Med, Div Geriatr & Palliat Med, Buffalo, NY 14260 USA. [Troen, Bruce R.] Vet Affairs Western New York Healthcare Syst, Buffalo, NY USA. [Ouslander, Joseph G.] Florida Atlantic Univ, Christine E Lynn Coll Nursing, Charles E Schmidt Coll Biomed Sci, Clin Biomed Sci, Boca Raton, FL 33431 USA. [Yoshikawa, Thomas] Univ Calif Los Angeles, David Geffen Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Yoshikawa, Thomas] Charles Drew Univ Med & Sci, Los Angeles, CA USA. RP Troen, BR (reprint author), SUNY Buffalo, Dept Med, Div Geriatr & Palliat Med, Buffalo, NY 14260 USA. NR 10 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 2015 VL 63 IS 8 BP 1693 EP 1693 DI 10.1111/jgs.13589 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CP9IG UT WOS:000360207000028 PM 26289687 ER PT J AU Iscan, S Seybert, C Erhardt, I Desmet, M Levy, RA Ablon, JS AF Iscan, Sureyya Seybert, Carolina Erhardt, Ingrid Desmet, Mattias Levy, Raymond A. Ablon, J. Stuart TI An Empirical Comparison of Short-Term Psychodynamic Psychotherapy Processes: Distinctive Process Factors Between Successful and Unsuccessful Therapeutic Outcome Groups SO JOURNAL OF THE AMERICAN PSYCHOANALYTIC ASSOCIATION LA English DT Article C1 [Iscan, Sureyya] Univ Massachusetts, Sch Med, Worcester, MA USA. [Seybert, Carolina] Int Psychoanalyt Univ, Berlin, Germany. [Erhardt, Ingrid] Univ Kassel, Kassel, Germany. [Desmet, Mattias] Univ Ghent, B-9000 Ghent, Belgium. [Levy, Raymond A.; Ablon, J. Stuart] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Iscan, S (reprint author), 14 South St,2, Westborough, MA 01581 USA. EM dr.iscan@verizon.net NR 7 TC 0 Z9 0 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0003-0651 EI 1941-2460 J9 J AM PSYCHOANAL ASS JI J. Am. Psychoanal. Assoc. PD AUG PY 2015 VL 63 IS 4 BP NP1 EP NP4 DI 10.1177/0003065115602878 PG 4 WC Psychiatry; Psychology, Psychoanalysis SC Psychiatry; Psychology GA CQ2BS UT WOS:000360405000001 PM 26316410 ER PT J AU Iglesias, JE Sabuncu, MR AF Eugenio Iglesias, Juan Sabuncu, Mert R. TI Multi-atlas segmentation of biomedical images: A survey SO MEDICAL IMAGE ANALYSIS LA English DT Article DE Multi-atlas segmentation; Label fusion; Survey ID BRAIN MRI SEGMENTATION; JOINT LABEL FUSION; SPATIALLY VARYING PERFORMANCE; MILD COGNITIVE IMPAIRMENT; EARLY ALZHEIMERS-DISEASE; TEMPORAL-LOBE EPILEPSY; AUTOMATIC SEGMENTATION; HIPPOCAMPAL SEGMENTATION; NONRIGID REGISTRATION; SELECTION-STRATEGIES AB Multi-atlas segmentation (MAS), first introduced and popularized by the pioneering work of Rohlfing, et al. (2004), Klein, et al. (2005), and Heckemann, et al. (2006), is becoming one of the most widely-used and successful image segmentation techniques in biomedical applications. By manipulating and utilizing the entire dataset of "atlases" (training images that have been previously labeled, e.g., manually by an expert), rather than some model-based average representation, MAS has the flexibility to better capture anatomical variation, thus offering superior segmentation accuracy. This benefit, however, typically comes at a high computational cost. Recent advancements in computer hardware and image processing software have been instrumental in addressing this challenge and facilitated the wide adoption of MAS. Today, MAS has come a long way and the approach includes a wide array of sophisticated algorithms that employ ideas from machine learning, probabilistic modeling, optimization, and computer vision, among other fields. This paper presents a survey of published MAS algorithms and studies that have applied these methods to various biomedical problems. In writing this survey, we have three distinct aims. Our primary goal is to document how MAS was originally conceived, later evolved, and now relates to alternative methods. Second, this paper is intended to be a detailed reference of past research activity in MAS, which now spans over a decade (2003-2014) and entails novel methodological developments and application-specific solutions. Finally, our goal is to also present a perspective on the future of MAS, which, we believe, will be one of the dominant approaches in biomedical image segmentation. (C) 2015 Elsevier B.V. All rights reserved. C1 [Eugenio Iglesias, Juan] Basque Ctr Cognit Brain & Language BCBL, Gipuzkoa, Spain. [Sabuncu, Mert R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Cambridge, MA 02138 USA. RP Sabuncu, MR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Cambridge, MA 02138 USA. EM e.iglesias@bcbl.eu; msabuncu@nmr.mgh.harvard.edu FU Gipuzkoako Foru Aldundia; NIH NIBIB [1K25EB013649-01]; BrightFocus Alzheimer's disease pilot research grant [AHAF-A2012333] FX Juan Eugenio Iglesias is supported by the Gipuzkoako Foru Aldundia (Fellows Gipuzkoa Program). Mert R. Sabuncu is supported by NIH NIBIB 1K25EB013649-01 and a BrightFocus Alzheimer's disease pilot research grant (AHAF-A2012333). NR 255 TC 35 Z9 35 U1 12 U2 30 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1361-8415 EI 1361-8423 J9 MED IMAGE ANAL JI Med. Image Anal. PD AUG PY 2015 VL 24 IS 1 BP 205 EP 219 DI 10.1016/j.media.2015.06.012 PG 15 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA CP9YV UT WOS:000360252700015 PM 26201875 ER PT J AU Hamblin, MR Chiang, LY Lakshmanan, S Huang, YY Garcia-Diaz, M Karimi, M Rastelli, AND Chandran, R AF Hamblin, Michael R. Chiang, Long Y. Lakshmanan, Shanmugamurthy Huang, Ying-Ying Garcia-Diaz, Maria Karimi, Mahdi de Souza Rastelli, Alessandra Nara Chandran, Rakkiyappan TI Nanotechnology for photodynamic therapy: a perspective from the Laboratory of Dr. Michael R. Hamblin in the Wellman Center for Photomedicine at Massachusetts General Hospital and Harvard Medical School SO NANOTECHNOLOGY REVIEWS LA English DT Article DE Hamblin Laboratory; nanotechnology; photodynamic therapy ID IN-VIVO; SCAVENGER-RECEPTOR; WOUND INFECTIONS; CANCER-CELLS; NANOPARTICLE PLATFORMS; OXYGEN PRODUCTION; DELIVERY VEHICLE; CELLULAR UPTAKE; ELECTRIC-FIELD; PHOTOSENSITIZER AB The research interests of the Hamblin Laboratory are broadly centered on the use of different kinds of light to treat many different diseases. Photodynamic therapy (PDT) uses the combination of dyes with visible light to produce reactive oxygen species and kill bacteria, cancer cells and destroy unwanted tissue. Likewise, UV light is also good at killing especially pathogens. By contrast, red or near-infrared light can have the opposite effect, to act to preserve tissue from dying and can stimulate healing and regeneration. In all these applications, nanotechnology is having an ever-growing impact. In PDT, self-assembled nano-drug carriers (micelles, liposomes, etc.) play a great role in solubilizing the photosensitizers, metal nanoparticles can carry out plasmon resonance enhancement, and fullerenes can act as photosensitizers, themselves. In the realm of healing, single-walled carbon nanotubes can be electrofocused to produce nano-electonic biomedical devices, and nanomaterials will play a great role in restorative dentistry. C1 [Hamblin, Michael R.; Lakshmanan, Shanmugamurthy; Huang, Ying-Ying] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.; Lakshmanan, Shanmugamurthy; Huang, Ying-Ying] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Chiang, Long Y.] Univ Massachusetts, Dept Chem, Lowell, MA USA. [Garcia-Diaz, Maria] Univ Copenhagen, Dept Pharm, DK-1168 Copenhagen, Denmark. [Karimi, Mahdi] Iran Univ Med Sci, Tehran, Iran. [de Souza Rastelli, Alessandra Nara] Univ Estadual Paulista, Araraquara Sch Dent, Sao Paulo, SP, Brazil. [Chandran, Rakkiyappan] Univ N Carolina, Joint Sch Nanosci & Nanoengn, Greensboro, NC 27412 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu FU US NIH [R01AI050875] FX Research in the Hamblin Laboratory is supported by US NIH grant R01AI050875. NR 97 TC 1 Z9 1 U1 3 U2 36 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 2191-9089 EI 2191-9097 J9 NANOTECHNOL REV JI Nanotechnol. Rev. PD AUG PY 2015 VL 4 IS 4 BP 359 EP 372 DI 10.1515/ntrev-2015-0027 PG 14 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA CP9HZ UT WOS:000360206200005 PM 26640747 ER PT J AU Bencherif, SA Sands, RW Ali, OA Li, WA Lewin, SA Braschler, TM Shih, TY Verbeke, CS Bhatta, D Dranoff, G Mooney, DJ AF Bencherif, Sidi A. Sands, R. Warren Ali, Omar A. Li, Weiwei A. Lewin, Sarah A. Braschler, Thomas M. Shih, Ting-Yu Verbeke, Catia S. Bhatta, Deen Dranoff, Glenn Mooney, David J. TI Injectable cryogel-based whole-cell cancer vaccines SO NATURE COMMUNICATIONS LA English DT Article ID COLONY-STIMULATING FACTOR; DENDRITIC CELLS; TUMOR-IMMUNOTHERAPY; IN-VIVO; PHASE-I; GM-CSF; MELANOMA; SAFETY; THERAPY; RESPONSES AB A biomaterial-based vaccination system that uses minimal extracorporeal manipulation could provide in situ enhancement of dendritic cell (DC) numbers, a physical space where DCs interface with transplanted tumour cells, and an immunogenic context. Here we encapsulate GM-CSF, serving as a DC enhancement factor, and CpG ODN, serving as a DC activating factor, into sponge-like macroporous cryogels. These cryogels are injected subcutaneously into mice to localize transplanted tumour cells and deliver immunomodulatory factors in a controlled spatio-temporal manner. These vaccines elicit local infiltrates composed of conventional and plasmacytoid DCs, with the subsequent induction of potent, durable and specific anti-tumour T-cell responses in a melanoma model. These cryogels can be delivered in a minimally invasive manner, bypass the need for genetic modification of transplanted cancer cells and provide sustained release of immunomodulators. Altogether, these findings indicate the potential for cryogels to serve as a platform for cancer cell vaccinations. C1 [Bencherif, Sidi A.; Sands, R. Warren; Ali, Omar A.; Li, Weiwei A.; Lewin, Sarah A.; Braschler, Thomas M.; Shih, Ting-Yu; Verbeke, Catia S.; Bhatta, Deen; Mooney, David J.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Bencherif, Sidi A.; Sands, R. Warren; Ali, Omar A.; Li, Weiwei A.; Lewin, Sarah A.; Braschler, Thomas M.; Shih, Ting-Yu; Verbeke, Catia S.; Bhatta, Deen; Mooney, David J.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Bencherif, Sidi A.] Univ Technol Compiegne, Univ Sorbonne, UTC CNRS UMR 7338, Biomech & Bioengn BMBI, F-60205 Compiegne, France. [Sands, R. Warren] Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA 15232 USA. [Braschler, Thomas M.] Ecole Polytech Fed Lausanne, Stn 17, LMIS4, Sch Engn, CH-1015 Lausanne, Switzerland. [Dranoff, Glenn] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Dranoff, Glenn] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02215 USA. [Dranoff, Glenn] Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. [Dranoff, Glenn] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Mooney, DJ (reprint author), Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. EM mooneyd@seas.harvard.edu FU National Institutes of Health [5R01DE019917-03, F30DK088518-03, T32-GM008152, 1UL1 TR001102]; Swiss National Fonds [PBELP3-133350] FX We thank Mr Thomas Ferrante and Dr James Weaver at the Wyss Institute for their technical assistance with confocal microscopy and scanning electron microscopy, respectively. This research was financially supported by the National Institutes of Health grants 5R01DE019917-03, F30DK088518-03 and T32-GM008152, and the Swiss National Fonds (grant PBELP3-133350). Dr. Roger B. Davis from the Harvard Catalyst Biostatistical Consulting Program funded by the National Institutes of Health (grant 1UL1 TR001102) is acknowledged. NR 56 TC 17 Z9 17 U1 5 U2 51 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 2015 VL 6 AR 7556 DI 10.1038/ncomms8556 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ1EI UT WOS:000360339700001 PM 26265369 ER PT J AU Chai, XJ Guo, Y Jiang, MX Hu, BF Li, ZG Fan, J Deng, MH Billiar, TR Kucera, HR Gaikwad, NW Xu, MS Lu, PP Yan, J Fu, HY Liu, YH Yu, LS Huang, M Zeng, S Xie, W AF Chai, Xiaojuan Guo, Yan Jiang, Mengxi Hu, Bingfang Li, Zhigang Fan, Jie Deng, Meihong Billiar, Timothy R. Kucera, Heidi R. Gaikwad, Nilesh W. Xu, Meishu Lu, Peipei Yan, Jiong Fu, Haiyan Liu, Youhua Yu, Lushan Huang, Min Zeng, Su Xie, Wen TI Oestrogen sulfotransferase ablation sensitizes mice to sepsis SO NATURE COMMUNICATIONS LA English DT Article ID IN-VIVO; KUPFFER CELLS; X-RECEPTOR; ACTIVATION; INJURY; LIVER; INFLAMMATION; SHOCK; TLR4; GENE AB Sepsis is the host's deleterious systemic inflammatory response to microbial infections. Here we report an essential role for the oestrogen sulfotransferase (EST or SULT1E1), a conjugating enzyme that sulfonates and deactivates estrogens, in sepsis response. Both the caecal ligation and puncture (CLP) and lipopolysaccharide models of sepsis induce the expression of EST and compromise the activity of oestrogen, an anti-inflammatory hormone. Surprisingly, EST ablation sensitizes mice to sepsis-induced death. Mechanistically, EST ablation attenuates sepsis-induced inflammatory responses due to compromised oestrogen deactivation, leading to increased sepsis lethality. In contrast, transgenic overexpression of EST promotes oestrogen deactivation and sensitizes mice to CLP-induced inflammatory response. The induction of EST by sepsis is NF-kappa B dependent and EST is a NF-kappa B-target gene. The reciprocal regulation of inflammation and EST may represent a yet-to-be-explored mechanism of endocrine regulation of inflammation, which has an impact on the clinical outcome of sepsis. C1 [Chai, Xiaojuan; Guo, Yan; Jiang, Mengxi; Hu, Bingfang; Xu, Meishu; Lu, Peipei; Yan, Jiong; Yu, Lushan; Xie, Wen] Univ Pittsburgh, Ctr Pharmacogenet, Pittsburgh, PA 15261 USA. [Chai, Xiaojuan; Guo, Yan; Jiang, Mengxi; Hu, Bingfang; Xu, Meishu; Lu, Peipei; Yan, Jiong; Yu, Lushan; Xie, Wen] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. [Chai, Xiaojuan; Yu, Lushan; Zeng, Su] Zhejiang Univ, Dept Pharmaceut Anal & Drug Metab, Coll Pharmaceut Sci, Zhejiang Prov Key Lab Anticanc Drug Res, Hangzhou 310058, Zhejiang, Peoples R China. [Guo, Yan] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Pathol, Shanghai 200025, Peoples R China. [Hu, Bingfang; Huang, Min] Sun Yat Sen Univ, Inst Clin Pharmacol, Guangzhou 510006, Guangdong, Peoples R China. [Li, Zhigang; Fan, Jie] Vet Affairs Pittsburgh Healthcare Syst, Surg Res, Pittsburgh, PA 15240 USA. [Fan, Jie; Deng, Meihong; Billiar, Timothy R.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15261 USA. [Kucera, Heidi R.; Gaikwad, Nilesh W.] Univ Calif Davis, Dept Nutr, Davis, CA 95616 USA. [Kucera, Heidi R.; Gaikwad, Nilesh W.] Univ Calif Davis, Dept Environm Toxicol, Davis, CA 95616 USA. [Fu, Haiyan; Liu, Youhua] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15261 USA. [Xie, Wen] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15261 USA. RP Zeng, S (reprint author), Zhejiang Univ, Dept Pharmaceut Anal & Drug Metab, Coll Pharmaceut Sci, Zhejiang Prov Key Lab Anticanc Drug Res, Hangzhou 310058, Zhejiang, Peoples R China. EM zengsu@zju.edu.cn; wex6@pitt.edu RI Xie, Wen/M-1768-2016 FU NIH [ES023438, DK099232, HD073070, HL079669, GM50441, GM53789]; VA Merit Award; Government of China's China Scholarship Council [2010632117] FX We thank Dr Gutian Xiao for the NF-kappa B reporter gene. This work was supported in part by the NIH grants ES023438, DK099232 and HD073070 (to W.X.), HL079669 (to J.F.), GM50441 (to T.R.B.), GM53789 (to T.R.B. and J.F.), and a VA Merit Award (to J.F.). X.C. is supported by a Scholarship from Government of China's China Scholarship Council (No. 2010632117). NR 36 TC 2 Z9 3 U1 4 U2 14 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 2015 VL 6 AR 7979 DI 10.1038/ncomms8979 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ1HC UT WOS:000360346900020 PM 26259151 ER PT J AU Janzen, DM Tiourin, E Salehi, JA Paik, DY Lu, J Pellegrini, M Memarzadeh, S AF Janzen, D. M. Tiourin, E. Salehi, J. A. Paik, D. Y. Lu, J. Pellegrini, M. Memarzadeh, S. TI An apoptosis-enhancing drug overcomes platinum resistance in a tumour-initiating subpopulation of ovarian cancer SO NATURE COMMUNICATIONS LA English DT Article ID NF-KAPPA-B; STEM-CELLS; FALLOPIAN-TUBE; IAP PROTEINS; CHEMOTHERAPY; ACTIVATION; THERAPY; TARGETS; CISPLATIN; DEATH AB High-grade serous ovarian cancers (HGSCs) are deadly malignancies that relapse despite carboplatin chemotherapy. Here we show that 16 independent primary HGSC samples contain a CA125-negative population enriched for carboplatin-resistant cancer initiating cells. Transcriptome analysis reveals upregulation of homologous recombination DNA repair and anti-apoptotic signals in this population. While treatment with carboplatin enriches for CA125-negative cells, co-treatment with carboplatin and birinapant eliminates these cells in HGSCs expressing high levels of the inhibitor of apoptosis protein cIAP in the CA125-negative population. Birinapant sensitizes CA125-negative cells to carboplatin by mediating degradation of cIAP causing cleavage of caspase 8 and restoration of apoptosis. This co-therapy significantly improves disease-free survival in vivo compared with either therapy alone in tumour-bearing mice. These findings suggest that therapeutic strategies that target CA125-negative cells may be useful in the treatment of HGSC. C1 [Janzen, D. M.; Tiourin, E.; Salehi, J. A.; Paik, D. Y.; Memarzadeh, S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA. [Lu, J.; Pellegrini, M.] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA. [Pellegrini, M.; Memarzadeh, S.] Univ Calif Los Angeles, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90095 USA. [Memarzadeh, S.] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. RP Memarzadeh, S (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA. EM smemarzadeh@mednet.ucla.edu OI Pellegrini, Matteo/0000-0001-9355-9564 FU NIH/NCI [R01CA183877]; American Cancer Society [VA CDA-2, RSG-14-217-01-TBG]; NIH/National Center for Advancing Translational Science UCLA CTSI [UL1TR000124]; Ovarian Cancer Circle Inspired by Robin Babbini; Leath L. and Marcia L. Millen Family Fund; Jonsson Cancer Center Foundation/UCLA; Lynne Cohen Foundation; Phase One Foundation; Gynecologic Oncology Discovery Lab Foundation FX We thank Drs Jeffery Gornbein, Jianyu Rao, Xinmin Li and Donghui Cheng for technical advice and support. We also thank the UCLA Eli and Edythe Broad Center of regenerative medicine and stem cell research FACS and microarray core facilities and the UCLA Translational Pathology Core Laboratory. Work in this manuscript was funded partly by an NIH/NCI R01CA183877 grant and a VA CDA-2 Award and largely by a Research Scholar Grant RSG-14-217-01-TBG from the American Cancer Society, an NIH/National Center for Advancing Translational Science UCLA CTSI Grant Number UL1TR000124, the Ovarian Cancer Circle Inspired by Robin Babbini, the Leath L. and Marcia L. Millen Family Fund, and funds from the Jonsson Cancer Center Foundation/UCLA, the Lynne Cohen Foundation, Phase One Foundation and the Gynecologic Oncology Discovery Lab Foundation. NR 60 TC 13 Z9 13 U1 0 U2 13 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 2015 VL 6 AR 7956 DI 10.1038/ncomms8956 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ1HA UT WOS:000360346700011 PM 26234182 ER PT J AU Lee, KY Singh, MK Ussar, S Wetzel, P Hirshman, MF Goodyear, LJ Kispert, A Kahn, CR AF Lee, Kevin Y. Singh, Manvendra K. Ussar, Siegfried Wetzel, Petra Hirshman, Michael F. Goodyear, Laurie J. Kispert, Andreas Kahn, C. Ronald TI Tbx15 controls skeletal muscle fibre-type determination and muscle metabolism SO NATURE COMMUNICATIONS LA English DT Article ID ACTIVATED PROTEIN-KINASE; GROWTH-FACTOR-II; GLUCOSE-TRANSPORT; FAT DISTRIBUTION; DIFFERENTIATION; TRANSCRIPTION; EXERCISE; OBESITY; PATHWAY; CELLS AB Skeletal muscle is composed of both slow-twitch oxidative myofibers and fast-twitch glycolytic myofibers that differentially impact muscle metabolism, function and eventually whole-body physiology. Here we show that the mesodermal transcription factor T-box 15 (Tbx15) is highly and specifically expressed in glycolytic myofibers. Ablation of Tbx15 in vivo leads to a decrease in muscle size due to a decrease in the number of glycolytic fibres, associated with a small increase in the number of oxidative fibres. This shift in fibre composition results in muscles with slower myofiber contraction and relaxation, and also decreases whole-body oxygen consumption, reduces spontaneous activity, increases adiposity and glucose intolerance. Mechanistically, ablation of Tbx15 leads to activation of AMPK signalling and a decrease in Igf2 expression. Thus, Tbx15 is one of a limited number of transcription factors to be identified with a critical role in regulating glycolytic fibre identity and muscle metabolism. C1 [Lee, Kevin Y.; Ussar, Siegfried; Hirshman, Michael F.; Goodyear, Laurie J.; Kahn, C. Ronald] Harvard Univ, Sch Med, Sect Integrat Physiol & Metab, Joslin Diabet Ctr, Boston, MA 02215 USA. [Singh, Manvendra K.; Kispert, Andreas] Hannover Med Sch, Inst Mol Biol, D-30625 Hannover, Germany. [Singh, Manvendra K.] Natl Heart Ctr Singapore, Duke NUS Grad Med Sch Singapore, Signature Res Program Cardiovasc & Metab Disorder, Singapore 169857, Singapore. [Ussar, Siegfried] Helmholtz Ctr, Inst Diabet & Obes, D-1385748 Munich, Germany. [Wetzel, Petra] Hannover Med Sch, Zentrum Physiol, D-30625 Hannover, Germany. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Sect Integrat Physiol & Metab, Joslin Diabet Ctr, 1 Joslin Plaza, Boston, MA 02215 USA. EM C.Ronald.Kahn@joslin.harvard.edu FU NIH [R01 DK 082655, RO1 AR042238]; Joslin DRC [P30 DK 036836]; Joslin training grant [T32DK007260]; American Diabetes Association mentor-based award; Mary K. Iacocca Professorship; German Research Council DFG [KI728/3]; iMed; Helmholtz Initiative on Personalized Medicine; German Center for Diabetes Research, DZD FX This work was supported by NIH grant R01 DK 082655 (C.R.K.), the Joslin DRC P30 DK 036836, the Joslin training grant T32DK007260, an American Diabetes Association mentor-based award (C.R.K.), the Mary K. Iacocca Professorship (C.R.K.), a grant from the German Research Council DFG KI728/3 (A.K.), iMed, the Helmholtz Initiative on Personalized Medicine (S.U.), the German Center for Diabetes Research, DZD (S.U.), and NIH grant RO1 AR042238 (L.J.G.). We thank Mary Frances Lopez (Boston Children's Hospital) for the Igf2 knockout mice and Dr Peter Rotwein (Oregon Health and Science University) for the Igf2 promoter constructs. We are grateful to Christie Penniman for animal care; and A. Clermont, M. Poillucci (DRC Physiology Core), H. Li (DRC Specialized Assay Core) and J. Schroeder (DRC Genomics Core) for technical assistance. NR 47 TC 5 Z9 5 U1 3 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD AUG PY 2015 VL 6 AR 8054 DI 10.1038/ncomms9054 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ1JE UT WOS:000360352600001 PM 26299309 ER PT J AU Mosimann, C Panakova, D Werdich, AA Musso, G Burger, A Lawson, KL Carr, LA Nevis, KR Sabeh, MK Zhou, Y Davidson, AJ DiBiase, A Burns, CE Burns, CG MacRae, CA Zon, LI AF Mosimann, Christian Panakova, Daniela Werdich, Andreas A. Musso, Gabriel Burger, Alexa Lawson, Katy L. Carr, Logan A. Nevis, Kathleen R. Sabeh, M. Khaled Zhou, Yi Davidson, Alan J. DiBiase, Anthony Burns, Caroline E. Burns, C. Geoffrey MacRae, Calum A. Zon, Leonard I. TI Chamber identity programs drive early functional partitioning of the heart SO NATURE COMMUNICATIONS LA English DT Article ID CARDIAC DEVELOPMENT; MOLECULAR-BASIS; ZEBRAFISH; FIELD; EXPRESSION; CELLS; MOUSE; GENE; PROGENITORS; LINEAGES AB The vertebrate heart muscle (myocardium) develops from the first heart field (FHF) and expands by adding second heart field (SHF) cells. While both lineages exist already in teleosts, the primordial contributions of FHF and SHF to heart structure and function remain incompletely understood. Here we delineate the functional contribution of the FHF and SHF to the zebrafish heart using the cis-regulatory elements of the draculin (drl) gene. The drl reporters initially delineate the lateral plate mesoderm, including heart progenitors. Subsequent myocardial drl reporter expression restricts to FHF descendants. We harnessed this unique feature to uncover that loss of tbx5a and pitx2 affect relative FHF versus SHF contributions to the heart. High-resolution physiology reveals distinctive electrical properties of each heart field territory that define a functional boundary within the single zebrafish ventricle. Our data establish that the transcriptional program driving cardiac septation regulates physiologic ventricle partitioning, which successively provides mechanical advantages of sequential contraction. C1 [Mosimann, Christian; Lawson, Katy L.; Carr, Logan A.; Zhou, Yi; Davidson, Alan J.; DiBiase, Anthony; Zon, Leonard I.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Mosimann, Christian; Lawson, Katy L.; Carr, Logan A.; Zhou, Yi; Davidson, Alan J.; DiBiase, Anthony; Zon, Leonard I.] Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Mosimann, Christian; Lawson, Katy L.; Carr, Logan A.; Zhou, Yi; Davidson, Alan J.; DiBiase, Anthony; Zon, Leonard I.] Harvard Univ, Boston Childrens Hosp, Sch Med, Div Hematol Oncol,Harvard Stem Cell Inst, Boston, MA 02115 USA. [Mosimann, Christian; Burger, Alexa] Univ Zurich, Inst Mol Life Sci IMLS, CH-8057 Zurich, Switzerland. [Panakova, Daniela; Werdich, Andreas A.; Musso, Gabriel; Sabeh, M. Khaled; MacRae, Calum A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. [Nevis, Kathleen R.; Burns, Caroline E.; Burns, C. Geoffrey] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP MacRae, CA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. EM camacrae@bics.bwh.harvard.edu; zon@enders.tch.harvard.edu OI Lawson, Katy/0000-0002-7712-9203; Panakova, Daniela/0000-0002-8739-6225 FU EMBO long-term fellowship; HFSP long-term fellowship; SNSF advanced researcher fellowship; SNF professorship; Marie Curie CIG; Helmholtz Young Investigator Program; March of Dimes; Harvard Stem Cell Institute; HHMI; NIH [5R01HL048801-19] FX We thank C. Lawrence, I. Adatto and K. Maloney for fish husbandry; Dr L. Cameron of the DFCI Imaging Core facility; Microscopy Core Facility at MDC for key imaging support; Drs D. Hesselson and D.Y. Stainier for the CY transgenesis marker; Dr I.C. Scott and Dr S. Abdelilah-Seyfried for providing myl7:nlsKikGR transgenics; and Dr G. Heffner and R. Mathieu for FACS support. We are grateful to Drs C. K. Kaufman and S.A. Lacadie for critical comments on experiments and the manuscript. C.M. received support through an EMBO long-term fellowship, an HFSP long-term fellowship, an SNSF advanced researcher fellowship, an SNF professorship, and a Marie Curie CIG; D.P. received support through an HFSP long-term fellowship, a Helmholtz Young Investigator Program and a Marie Curie CIG; C.A.M. received support from the March of Dimes and the Harvard Stem Cell Institute; L.I.Z. is supported by HHMI and NIH 5R01HL048801-19. NR 47 TC 11 Z9 12 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD AUG PY 2015 VL 6 AR 8146 DI 10.1038/ncomms9146 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ1KM UT WOS:000360356500002 PM 26306682 ER PT J AU Deckers, K De Smedt, K van Buyten, JP Smet, I Eldabe, S Gulve, A Baranidharan, G de Andres, J Gilligan, C Jaax, K Heemels, JP Crosby, P AF Deckers, Kristiaan De Smedt, Kris van Buyten, Jean-Pierre Smet, Iris Eldabe, Sam Gulve, Ashish Baranidharan, Ganesan de Andres, Jose Gilligan, Chris Jaax, Kristen Heemels, Jan Pieter Crosby, Peter TI Chronic Low Back Pain: Restoration of Dynamic Stability SO NEUROMODULATION LA English DT Article DE Low back pain; motor control; multifidus; quality of life; stimulation ID LUMBAR MULTIFIDUS MUSCLE; NEUROMUSCULAR ELECTRICAL-STIMULATION; TOTAL KNEE ARTHROPLASTY; HEALTHY-SUBJECTS; CONTRACTION; TRIAL; CLASSIFICATION; PERFORMANCE; INHIBITION; MODULATION AB ObjectivesElectrical stimulation for multifidus muscle contraction is a novel approach for treating chronic low back pain (CLBP). A multicenter, open-label feasibility study investigated this modality in patients with continuing CLBP despite medical management and no prior back surgery and no known pathological cause of CLBP. MethodsTwenty-six patients with continuing CLBP despite physical therapy and medication were implanted with commercially-available implantable pulse generators and leads positioned adjacent to the medial branch of the dorsal ramus as it crosses the L3 transverse process such that electrical stimulation resulted in contraction of the lumbar multifidus (LM) muscle. Patients self-administered stimulation twice daily for 20min. Low back pain (VAS), Oswestry Disability Index (ODI) and Quality of Life (EQ-5D) scores were collected at three and five months and compared to baseline. Stimulation was withdrawn between months 4 and 5 to test durability of effect. ResultsAt three months, 74% of patients met or exceeded the minimally important change (MIC) in VAS and 63% for disability. QoL improved in 84% of patients (N = 19) and none got worse. Five of the 11 patients on disability for CLBP (45%) resumed work by three months. Half the patients reported 50% VAS reduction by month 5. Twenty-one lead migration events occurred in 13 patients, of which 7 patients are included in the efficacy cohort. ConclusionsEpisodic stimulation to induce LM contraction can reduce CLBP and disability, improve quality of life and enable return to work. A dedicated lead design to reduce risk of migration is required. C1 [Deckers, Kristiaan] GZA Hosp, Dept Phys Med & Rehabil, Antwerp, Belgium. [De Smedt, Kris] GZA Hosp, Dept Neurosurg, Antwerp, Belgium. [van Buyten, Jean-Pierre; Smet, Iris] AZ Nikolaas, Ctr Multidisciplinary Pain, St Niklaas, Belgium. [Eldabe, Sam; Gulve, Ashish] James Cook Univ Hosp, Dept Pain & Anaesthesia, Middlesbrough, Cleveland, England. [Baranidharan, Ganesan] Leeds Teaching Hosp NHS Trust, Leeds Pain & Neuromodulat Ctr, Leeds, W Yorkshire, England. [de Andres, Jose] Gen Univ Hosp, Anesthesia Crit Care & Pain Management, Valencia, Spain. [Gilligan, Chris] Massachusetts Gen Hosp, Ctr Pain Med, Boston, MA 02114 USA. [Jaax, Kristen; Heemels, Jan Pieter; Crosby, Peter] Mainstay Med Ltd, Swords, Ireland. RP Deckers, K (reprint author), GZA Ziekenhuizen, Diensthoofd Fys Geneeskunde & Revalidatie, Oosterveldlaan 24, B-2610 Antwerp, Belgium. EM kristiaan.deckers@gza.be FU Mainstay Medical Limited FX This study was sponsored by Mainstay Medical Limited. NR 47 TC 1 Z9 1 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1094-7159 EI 1525-1403 J9 NEUROMODULATION JI Neuromodulation PD AUG PY 2015 VL 18 IS 6 BP 478 EP 486 DI 10.1111/ner.12275 PG 9 WC Medicine, Research & Experimental; Clinical Neurology SC Research & Experimental Medicine; Neurosciences & Neurology GA CQ3KK UT WOS:000360500700008 PM 25683776 ER PT J AU Barth, WH AF Barth, William H., Jr. TI Persistent Occiput Posterior SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material AB Persistent occiput posterior (OP) position, when the fetal occiput stays in the posterior of the maternal pelvis until the time of delivery, has an incidence of 5% to 12%. Persistent OP can be influenced by epidural analgesia, parity, race, and shape of the pelvis. When discovered in the active or early second stages of labor, OP often resolves without effort. When it does not spontaneously resolve, persistent OP and complications may be reduced by prophylactic manual rotation. Other methods for resolution include nonrotational operative vaginal delivery, the use of rotational forceps, or, increasingly, cesarean delivery. This article is a comprehensive review of the outcomes and management of the persistent OP fetus. Studies have demonstrated that OP is associated with longer first and second stages of labor, the need for labor augmentation, and higher rates of cesarean delivery, operative vaginal delivery, failed operative vaginal delivery, and third- and fourth-degree perineal lacerations. During intrapartum care, OP is associated with a higher rate of abnormal fetal heart patterns. Occiput posterior newborns have been found to have higher rates of low Apgar scores (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.17-1.91), meconium (OR, 1.29; 95% CI, 1.17-1.42), birth trauma (OR, 1.77; 95% CI, 1.22-2.57), cord gas acidemia (OR, 2.05; 95% CI, 1.52-2.77), and neonatal intensive care unit admission (OR, 1.57; 95% CI, 1.28-1.92). While diagnosis is typically made using physical examination, this is often inaccurate prior to full cervix dilation. Ultrasonography can also be used for diagnosis and can be more accurate during the second stage of labor than digital vaginal examinations. The author of the review believes ultrasonography is not necessary before all operative vaginal deliveries. The author does recommend the following guidelines when consulting on a persistent OP before the onset of labor, as no prelabor interventions are effective in reduction of persistent OP. During the first stage of labor, maternal positioning to encourage rotation of the occiput has not been supported by evidence. In the early second stage, there is no need for intervention for OP if labor is progressing, but if OP continues later into the second stage, when the likelihood of spontaneous rotation decreases, and adverse outcomes become more likely, the options at that point to facilitate rotation are forceps rotation or manual rotation. The decreasing number of clinicians who will perform or teach rotations with Kielland forceps presents a challenge. While not all residents should be trained for proficiency in procedures such as this, those who are trained in Kielland forceps should be willing to perform and teach the procedure. Manual rotation may be easier to teach and have a wider acceptance by clinicians and patients alike. In a prospective study, Reichman and colleagues found deliveries that underwent prophylactic rotation halfway into the second stage were more likely to be occiput anterior at delivery compared with an expectant management group (93% compared with 15%, P < 0.001) and more likely to deliver vaginally. In summary, persistent OP appears to contribute to the particularly high cesarean delivery rate and deserves attention by obstetric clinicians. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Div Maternal Fetal Med, Boston, MA 02163 USA. RP Barth, WH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Div Maternal Fetal Med, Boston, MA 02163 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7828 EI 1533-9866 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD AUG PY 2015 VL 70 IS 8 BP 485 EP 486 DI 10.1097/01.ogx.0000470658.66200.86 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CP8KS UT WOS:000360143200004 ER PT J AU Saxena, R Georgopoulos, NA Braaten, TJ Bjonnes, AC Koika, V Panidis, D Welt, CK AF Saxena, R. Georgopoulos, N. A. Braaten, T. J. Bjonnes, A. C. Koika, V. Panidis, D. Welt, C. K. TI Han Chinese Polycystic Ovary Syndrome Risk Variants in Women of European Ancestry: Relationship to FSH Levels and Glucose Tolerance EDITORIAL COMMENT SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material AB Polycystic ovary syndrome (PCOS) affects 7% to 10% of reproductive-age women. The etiology of the syndrome is poorly understood. Twin studies suggest that the pathogenesis of PCOS in more than 70% of cases can be explained by genetic influences. Risk loci for genetic variants associated with the syndrome have been identified in women of Han Chinese ethnicity. Two genome-wide association studies in Han Chinese women identified risk loci for 11 genetic variants. Three of these 11 variants were also associated with PCOS in at least 1 European population when corrected for multiple testing, including DENND1A, THADA, and YAP1. The PCOS variants identified require additional replication in Greek and US women to establish the importance of these variants and to determine their relationship to PCOS phenotypic traits. This case-control study was designed to investigate whether PCOS risk variants identified in women of Han Chinese ethnicity were also associated with risk of PCOS or its phenotypic features in European and US women. The discovery cohort was composed of women with PCOS (n = 485) and control subjects (n = 407) from Boston (Boston 1). Susceptibility variants were examined in replicate populations in Greece (cases n = 884 and control subjects n = 311), and a second cohort from Boston identified through the electronic medical record (EMR), n = 350 cases and n = 1258 control subjects). Women in Boston 1 and Greece (n = 783) had PCOS defined by the National Institutes of Health criteria (irregular menses and clinical or biochemical hyperandrogenism [n = 527]), with additional subjects fulfilling the Rotterdam criteria (clinical or biochemical hyperandrogenism, polycystic ovary morphology, and regular menstrual cycles [n = 101]). Control subjects in Boston and Greece had regular menses and no hyperandrogenism. The second Boston cohort was defined using the EMR and natural language processing. Allele frequencies for PCOS risk variants identified in Han Chinese women were examined in PCOS cases and control subjects, along with the relationship to quantitative traits. One variant, rs2268361-T, in the intron of follicle-stimulating hormone receptor (FSHR) was associated with PCOS; the combined odds ratio was 0.84 (95% confidence interval, 0.76-0.93; P = 0.002). This variant was associated with lower follicle-stimulating hormone (FSH) levels (-0.15 0.05; P = 0.0029). Another variant, rs705702-G, near the RAB5B and SUOX genes, was associated with lower insulin (-0.16 0.05; P = 0.0029) and glucose levels (-0.20 0.05; P = 0.0002) 120 minutes after an oral glucose test, suggesting better insulin sensitivity. Although the study was large and contained replication cohorts, the findings were limited by a small number of control subjects in the Greek cohort and a small number of cases in the second Boston cohort. Moreover, it was possible that the second Boston cohort identified with EMR review could contribute to the observed differences; this cohort, however, was validated for the cardinal features of PCOS. These findings show that a PCOS risk variant present in Han Chinese women in the region of FSHR is also associated with PCOS in women of European ethnicity. This cross-ethnic PCOS risk locus, rs2268361-T, may influence FSH receptor responsiveness as suggested by the associated change in FSH levels and suggest that disrupting FSH stimulation of follicle development is a key etiologic feature of PCOS. The association between the rs705702-G variant near the RAB5B and SUOX genes and glucose-stimulated insulin and glucose levels suggests that 1 of these genes could influence insulin resistance in women with PCOS; the absence of a relationship with PCOS, however, points to potential differences in the international PCOS patient populations. C1 [Saxena, R.; Bjonnes, A. C.] Massachusetts Gen Hosp, Dept Anaesthesia, Boston, MA 02114 USA. [Saxena, R.; Bjonnes, A. C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Georgopoulos, N. A.; Koika, V.; Panidis, D.] Univ Patras, Sch Med, Dept Obstet & Gynecol, Div Reprod Endocrinol, GR-26110 Patras, Greece. [Braaten, T. J.] Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA. [Panidis, D.] Aristotle Univ Thessaloniki, Dept Obstet & Gynecol 2, Div Endocrinol & Human Reprod, Thessaloniki, Greece. [Welt, C. K.] Univ Utah, Div Endocrinol Metab & Diabet, Salt Lake City, UT USA. RP Saxena, R (reprint author), Massachusetts Gen Hosp, Dept Anaesthesia, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7828 EI 1533-9866 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD AUG PY 2015 VL 70 IS 8 BP 509 EP 510 DI 10.1097/01.ogx.0000470815.31329.4c PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CP8KS UT WOS:000360143200017 ER PT J AU Zeitels, SM AF Zeitels, Steven M. TI Transoral and Transcervical Surgical Innovations in the Treatment of Glottic Cancer SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Vocal cord cancer; Glottic cancer; Larynx cancer; Phonosurgery; Phonomicrosurgery; Airway reconstruction; Voice outcome ID KTP LASER TREATMENT; PARTIAL LARYNGECTOMY; CLINICAL EXPERIENCE; CO2-LASER; SURGERY; RECONSTRUCTION; CARCINOMA; TRACHEA; LARYNX; VOICE AB Transoral and transcervical surgery to treat glottic cancer has advanced substantially over the past decade. There have been considerable innovations that enhance vocal function for early disease and airway function for advanced disease. The fiber-based angiolytic 532 nm potassium titanyl phosphate laser has provided a new foundational strategy to maintain high cure rates with enhanced vocal outcomes for the treatment of early glottic disease. For advanced glottic cancer, transplanting cryopreserved aortic homograft to reconstruct wide-field laryngotracheal airway defects can provide an adequate airway caliber such that a long-term tracheotomy can frequently be avoided. C1 [Zeitels, Steven M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Laryngeal Surg, Boston, MA 02114 USA. RP Zeitels, SM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Laryngeal Surg, One Bowdoin Sq, Boston, MA 02114 USA. EM zeitels.steven@mgh.harvard.edu FU Voice Health Institute; "V" Foundation; Eugene B. Casey Foundation; National Philanthropic Trust FX This work was supported in part by the Voice Health Institute, The "V" Foundation, the Eugene B. Casey Foundation, and the National Philanthropic Trust. NR 23 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0030-6665 EI 1557-8259 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD AUG PY 2015 VL 48 IS 4 BP 677 EP + DI 10.1016/j.otc.2015.04.012 PG 10 WC Otorhinolaryngology SC Otorhinolaryngology GA CQ0YO UT WOS:000360324700012 PM 26233792 ER PT J AU Chen, CX Guan, XD Quinn, DA Ouyang, B AF Chen, Chuanxi Guan, Xiangdong Quinn, Deborah A. Ouyang, Bin TI N-Acetylcysteine Inhibits Ventilation-Induced Collagen Accumulation in the Rat Lung SO TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE antioxidant; collagen; mechanical ventilation; N-acetylcysteine; pulmonary fibrosis ID RESPIRATORY-DISTRESS-SYNDROME; OXIDATIVE STRESS; MECHANICAL VENTILATION; INJURY; FIBROSIS; STRETCH; INFLAMMATION; EXPRESSION; TISSUE; CELLS AB Mechanical ventilation is the most important life supportive therapy for patients with acute respiratory distress syndrome (ARDS). However, increasing evidence from clinical studies suggests that mechanical ventilation can cause lung fibrosis, which may significantly contribute to morbidity and mortality. Recent studies also found fibroproliferation occurred in early stage of ARDS with poor outcome. We have hypothesized that mechanical ventilation-induced lung injury may be a major contributor to lung fibrosis, and antioxidant could be a potential therapeutic agent for the treatment to mechanic ventilation induced fibroproliferation. We therefore used Sprague-Dawley rats that were ventilated with large tidal volume (20 ml/kg) or low tidal volume (7 ml/kg). We analyzed the time course of collagen level in the lung and the effect of N-acetylcysteine (NAC), a thiol antioxidant, on mechanical ventilation-induced collagen accumulation. In addition, normal human lung fibroblasts (NHLF) were exposed to mechanical stretch, which mimics ventilator-induced lung inflation, to evaluate the collagen secretion in culture medium. We found that ventilation-induced collagen accumulation occurred even after 2-hour ventilation. Pretreatment with NAC (140 mg/kg) inhibited collagen accumulation in lungs of rats ventilated with large tidal volume. Moreover, mechanical stretch caused the accumulation of collagen in the culture medium of NHLF, the magnitude of which was decreased with the pretreatment with NAC (1 nnM). These results indicate that mechanical ventilation can induce collagen accumulation within 2 hours. NAC alleviated the collagen accumulation induced by mechanical ventilation with high tidal volume. Therefore, NAC can be considered as a good candidate in preventing ventilation-induced lung fibrosis. C1 [Chen, Chuanxi; Guan, Xiangdong; Ouyang, Bin] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Crit Care Med, Guangzhou 510080, Guangdong, Peoples R China. [Quinn, Deborah A.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Quinn, Deborah A.] Harvard Univ, Sch Med, Boston, MA USA. RP Ouyang, B (reprint author), Sun Yat Sen Univ, Affiliated Hosp 1, Dept Crit Care Med, 58 Zhongshan Er Lu, Guangzhou 510080, Guangdong, Peoples R China. EM binouyang@yahoo.com FU National Natural Science Foundation of China [81071536] FX The authors thank Yang Xia and Fengyang Lei for providing language help. This work was supported by the grant from the National Natural Science Foundation of China No. 81071536. NR 34 TC 1 Z9 1 U1 1 U2 5 PU TOHOKU UNIV MEDICAL PRESS PI SENDAI PA 2-1, SEIRYO-MACHI, AOBA-KU, SENDAI, MIYAGI 980-8575, JAPAN SN 0040-8727 EI 1349-3329 J9 TOHOKU J EXP MED JI Tohoku J. Exp. Med. PD AUG PY 2015 VL 236 IS 4 BP 255 EP 261 DI 10.1620/tjem.236.255 PG 7 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA CP9YG UT WOS:000360251200003 PM 26156407 ER PT J AU Wells, DM Lehavot, K Isaac, ML AF Wells, Deva M. Lehavot, Keren Isaac, Margaret L. TI Sounding Off on Social Media: The Ethics of Patient Storytelling in the Modern Era SO ACADEMIC MEDICINE LA English DT Article ID ONLINE PROFESSIONALISM; HEALTH-PROFESSIONALS; NETWORKING; STUDENTS; CARE; PERCEPTIONS; REFLECTION; PHYSICIANS AB Use of social networking programs like Facebook and Twitter, which enable the public sharing of diverse content over the Internet, has risen dramatically in recent years. Although health professionals have faced consequences for clearly unethical online behavior, a relatively unexamined practice among medical students is the disclosure of patient care stories on social media in a manner that is technically compliant with the Health Insurance Portability and Accountability Act, yet is ethically questionable. In this Perspective, the authors review three such cases in which students do not specifically reveal a patient's identity but share details of a personal nature, motivated by a variety of intentions (e.g., a desire to reflect on a meaningful experience, reaching out for social support in the event of a patient's death). Using ethical principles and professional policy recommendations, they discuss aspects of these postings that are potentially problematic. Consequences include the possibility of undermining public trust in the profession, inadvertently identifying patients, and violating expectations of privacy. The authors recommend that medical schools explicitly address these issues across the preclinical and clinical curricula and emphasize that patient-related postings on social media may carry inherent risks both to patients and to the profession. C1 [Wells, Deva M.] Univ Washington, Sch Med, Seattle, WA USA. [Lehavot, Keren] Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA USA. [Lehavot, Keren] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Isaac, Margaret L.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. RP Wells, DM (reprint author), 1959 NE Pacific St, Seattle, WA 98195 USA. EM devaw@uw.edu NR 36 TC 12 Z9 12 U1 4 U2 19 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 2015 VL 90 IS 8 BP 1015 EP 1019 DI 10.1097/ACM.0000000000000668 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA CP3EU UT WOS:000359761100011 PM 25692559 ER PT J AU Hesketh, RL Zhu, AX Oklu, R AF Hesketh, Richard L. Zhu, Andrew X. Oklu, Rahmi TI Hepatocellular Carcinoma Can Circulating Tumor Cells and Radiogenomics Deliver Personalized Care? SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Review DE hepatocellular carcinoma; radiogenomics; circulating tumor cells ID GENE-EXPRESSION PROGRAMS; RECURRENT MUTATIONS; CIRRHOTIC-PATIENTS; SOMATIC MUTATIONS; BETA-CATENIN; LIVER-CANCER; SURVIVAL; PREDICTION; PATHWAYS AB The 'omics revolution is facilitating a personalized approach to improving outcome by refining diagnosis, staging, treatment, and monitoring of hepatocellular carcinoma. Furthermore, the promise of being able to target a range of specific tumor drivers at a molecular level offers exciting new therapy prospects for a disease that is notoriously difficult to treat. We provide a unique perspective combining our understanding of the molecular mechanisms of hepatocellular carcinoma development with the potential of circulating tumor cells and radiogenomics to change the drivers of decision-making used in current practice. C1 [Hesketh, Richard L.] West Middlesex Univ Hosp, London, England. [Zhu, Andrew X.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA USA. [Oklu, Rahmi] Massachusetts Gen Hosp, Div Vasc Imaging & Intervent, Boston, MA 02114 USA. [Zhu, Andrew X.; Oklu, Rahmi] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Oklu, R (reprint author), Massachusetts Gen Hosp, Div Vasc Imaging & Intervent, 55 Fruit St,290 Gray Bigelow, Boston, MA 02114 USA. EM roklu@mgh.harvard.edu FU NCI NIH HHS [R03 CA172738] NR 43 TC 2 Z9 2 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-3732 EI 1537-453X J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD AUG PY 2015 VL 38 IS 4 BP 431 EP 436 DI 10.1097/COC.0000000000000123 PG 6 WC Oncology SC Oncology GA CP4EQ UT WOS:000359835200019 PM 25238287 ER PT J AU Park, YI Im, H Weissleder, R Lee, H AF Park, Yong Il Im, Hyungsoon Weissleder, Ralph Lee, Hakho TI Nanostar Clustering Improves the Sensitivity of Plasmonic Assays SO BIOCONJUGATE CHEMISTRY LA English DT Article ID GOLD NANOSTARS; RESONANCE SPECTROSCOPY; SILVER NANOPARTICLES; OPTIMIZATION; NANOPRISMS; LENGTH AB Star-shaped Au nanoparticles (Au nanostars, AuNS) have been developed to improve the plasmonic sensitivity, but their application has largely been limited to single-particle probes. We herein describe a AuNS clustering assay based on nanoscale self-assembly of multiple AuNS and which further increases detection sensitivity. We show that each cluster contains multiple nanogaps to concentrate electric fields, thereby amplifying the signal via plasmon coupling. Numerical simulation indicated that AuNS clusters assume up to 460-fold higher field density than Au nanosphere clusters of similar mass. The results were validated in model assays of protein biomarker detection. The AuNS clustering assay showed higher sensitivity than Au nanosphere. Minimizing the size of affinity ligand was found important to tightly confine electric fields and improve the sensitivity. The resulting assay is simple and fast and can be readily applied to point-of-care molecular detection schemes. C1 [Park, Yong Il; Im, Hyungsoon; Weissleder, Ralph; Lee, Hakho] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02114 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu; hlee@mgh.harvard.edu RI Im, Hyungsoon/A-3178-2009 OI Im, Hyungsoon/0000-0002-0626-1346 FU NIH [R01HL113156, R01EB004626, R01EB010011, HHSN268201000044C, U54-CA119349, T32-CA79443]; Department of Defense OCRP Program [W81XWH-14-1-0279] FX We thank K. Lee for microscopy imaging and H. Shao and H. J. Chung for helpful discussions. This work was supported in part by NIH Grants R01HL113156, R01EB004626, R01EB010011, HHSN268201000044C, U54-CA119349, and T32-CA79443 and Department of Defense OCRP Program Award W81XWH-14-1-0279. NR 27 TC 4 Z9 5 U1 9 U2 40 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD AUG PY 2015 VL 26 IS 8 BP 1470 EP 1474 DI 10.1021/acs.bioconjchem.5b00343 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA CP5ZA UT WOS:000359962900010 PM 26102604 ER PT J AU Kim, E Yang, KS Kohler, RH Dubach, JM Mikula, H Weissleder, R AF Kim, Eunha Yang, Katherine S. Kohler, Rainer H. Dubach, John M. Mikula, Hannes Weissleder, Ralph TI Optimized Near-IR Fluorescent Agents for in Vivo Imaging of Btk Expression SO BIOCONJUGATE CHEMISTRY LA English DT Article ID BRUTONS-TYROSINE-KINASE; CHRONIC LYMPHOCYTIC-LEUKEMIA; MANTLE-CELL LYMPHOMA; TARGETING BTK; SI-RHODAMINE; LIVE-CELL; INHIBITOR; IBRUTINIB; FLUOROPHORES; MALIGNANCIES AB Bruton's tyrosine kinase (Btk) is intricately involved in anti-apoptotic signaling pathways in cancer and in regulating innate immune response. A number of Btk inhibitors are in development for use in treating B-cell malignancies and certain immunologic diseases. To develop robust companion imaging diagnostics for in vivo use, we set out to explore the effects of red wavelength fluorochrome modifications of two highly potent irreversible Btk inhibitors, Ibrutinib and AVL-292. Surprisingly, we found that subtle chemical differences in the fluorochrome had considerable effects on target localization. Based on iterative designs, we developed a single optimized version with superb in vivo imaging characteristics enabling single cell Btk imaging in vivo. This agent (Ibrutinib-SiR-COOH) is expected to be a valuable chemical tool in deciphering Btk biology in cancer and host cells in vivo. C1 [Kim, Eunha; Yang, Katherine S.; Kohler, Rainer H.; Dubach, John M.; Mikula, Hannes; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu FU National Institutes of Health (NIH) [T32CA079443, P50CA086355, R01EB010011] FX We are grateful to David Pirovich for imaging assistance and Dr. Ralph Mazitschek for many helpful discussions. The authors acknowledge funding from National Institutes of Health (NIH) grants T32CA079443 and P50CA086355, and in part by R01EB010011. In compliance with Partners Healthcare/Harvard Medical School institutional guidelines, R.W. discloses his financial interest in Lumicell, a biotechnology company developing intraoperative imaging systems for surgical applications. Lumicell did not support the research herein, and the company has no rights to any technology or intellectual property developed as part of this research. NR 35 TC 7 Z9 7 U1 4 U2 20 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD AUG PY 2015 VL 26 IS 8 BP 1513 EP 1518 DI 10.1021/acs.bioconjchem.5b00152 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA CP5ZA UT WOS:000359962900016 PM 26017814 ER PT J AU Moayyedi, P Quigley, EMM Lacy, BE Lembo, AJ Saito, YA Schiller, LR Soffer, EE Spiegel, BMR Ford, AC AF Moayyedi, Paul Quigley, Eamonn M. M. Lacy, Brian E. Lembo, Anthony J. Saito, Yuri A. Schiller, Lawrence R. Soffer, Edy E. Spiegel, Brennan M. R. Ford, Alexander C. TI The Effect of Dietary Intervention on Irritable Bowel Syndrome: A Systematic Review SO CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY LA English DT Review ID FUNCTIONAL GASTROINTESTINAL DISORDERS; RANDOMIZED CONTROLLED-TRIAL; CELIAC WHEAT SENSITIVITY; GLUTEN-FREE DIET; FOOD HYPERSENSITIVITY; GAS-PRODUCTION; SYMPTOMS; METAANALYSIS; INTOLERANCE; MANAGEMENT AB OBJECTIVES: Elimination diets have been used for many years to treat irritable bowel syndrome (IBS). These approaches had fallen out of favor until a recent resurgence, which was based on new randomized controlled trial (RCT) data that suggested it might be effective. The evidence for the efficacy of dietary therapies has not been evaluated systematically. We have therefore conducted a systematic review to examine this issue. METHODS: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched up to December 2013. Trials recruiting adults with IBS, which compared any form of dietary restriction or addition of an offending food group in patients already on a restricted diet vs. placebo, control therapy, or "usual management", were eligible. Dichotomous symptom data were pooled to obtain a relative risk of remaining symptomatic after therapy as well as the number needed to treat with a 95% confidence interval. RESULTS: We identified 17 RCTs involving 1,568 IBS patients that assessed elimination diets. Only three RCTs involving 230 patients met our eligibility criteria, all of which evaluated different approaches, and thus a meta-analysis could not be conducted. CONCLUSIONS: More evidence is needed before generally recommending elimination diets for IBS patients. C1 [Moayyedi, Paul] McMaster Univ, Hlth Sci Ctr, Farncombe Family Digest Hlth Res Inst, Hamilton, ON L8N 3Z5, Canada. [Quigley, Eamonn M. M.] Houston Methodist Hosp, Dept Med, Div Gastroenterol & Hepatol, Houston, TX USA. [Lacy, Brian E.] Dartmouth Hitchcock Med Ctr, Div Gastroenterol & Hepatol, Lebanon, NH 03766 USA. [Lembo, Anthony J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Saito, Yuri A.] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. [Schiller, Lawrence R.] Baylor Univ, Med Ctr, Digest Hlth Associates Texas, Dallas, TX USA. [Soffer, Edy E.] Univ So Calif, Div Gastroenterol Cedars Sinai, Los Angeles, CA USA. [Spiegel, Brennan M. R.] VA Greater Los Angeles Healthcare Syst, Dept Gastroenterol, Los Angeles, CA USA. [Ford, Alexander C.] St James Univ Hosp, Leeds Gastroenterol Inst, Leeds, W Yorkshire, England. [Ford, Alexander C.] Univ Leeds, Leeds Inst Biomed & Clin Sci, Leeds, W Yorkshire, England. RP Moayyedi, P (reprint author), McMaster Univ, Hlth Sci Ctr, Farncombe Family Digest Hlth Res Inst, Hamilton, ON L8N 3Z5, Canada. EM moayyep@mcmaster.ca RI Ford, Alexander/K-5491-2012 OI Ford, Alexander/0000-0001-6371-4359 FU American College of Gastroenterology FX American College of Gastroenterology. NR 36 TC 10 Z9 10 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2155-384X J9 CLIN TRANSL GASTROEN JI Clin. Transl. Gastroenterol. PD AUG PY 2015 VL 6 AR e107 DI 10.1038/ctg.2015.21 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CP8FM UT WOS:000360127700002 PM 26291435 ER PT J AU Kraut, JA AF Kraut, Jeffrey A. TI Diagnosis of toxic alcohols: limitations of present methods SO CLINICAL TOXICOLOGY LA English DT Review DE Toxic alcohols; Serum osmolal gap; Serum anion gap; Fomepizole; Methanol; Ethylene glycol; Propylene glycol ID HYPEROSMOLAR METABOLIC-ACIDOSIS; PROPYLENE-GLYCOL TOXICITY; ETHYLENE-GLYCOL; DIETHYLENE GLYCOL; OSMOLAL GAP; ANION-GAP; INTRAVENOUS LORAZEPAM; PRACTICE GUIDELINES; URINE FLUORESCENCE; AMERICAN-ACADEMY AB Context. Methanol, ethylene glycol, diethylene glycol, and propylene glycol intoxications are associated with cellular dysfunction and an increased risk of death. Adverse effects can develop quickly; thus, there is a need for methods for rapidly detecting their presence. Objective. To examine the value and limitations of present methods to diagnose patients with possible toxic alcohol exposure. Methods. I searched MEDLINE for articles published between 1969 and 2014 using the terms: toxic alcohols, serum osmolality, serum osmol gap, serum anion gap, metabolic acidosis, methanol, ethylene glycol, diethylene glycol, propylene glycol, and fomepizole. Each article was reviewed for additional references. Results. The diagnosis of toxic alcohol exposure is often made on the basis of this history and physical findings along with an increase in the serum osmol and anion gaps. However, an increase in the osmol and/or anion gaps is not always present. Definitive detection in blood requires gas or liquid chromatography, laborious and expensive procedures which are not always available. Newer methods including a qualitative colorimetric test for detection of all alcohols or enzymatic tests for a specific alcohol might allow for more rapid diagnosis. Conclusions. Exposure to toxic alcohols is associated with cellular dysfunction and increased risk of death. Treatment, if initiated early, can markedly improve outcome, but present methods of diagnosis including changes in serum osmol and anion gap, and use of gas or liquid chromatography have important limitations. Development of more rapid and effective tests for detection of these intoxications is essential for optimal care of patients. C1 [Kraut, Jeffrey A.] Univ Calif Los Angeles, Membrane Biol Lab, Med & Res Serv Vet Adm Greater Los Angeles Health, Los Angeles, CA USA. [Kraut, Jeffrey A.] Vet Adm Greater Los Angeles Healthcare Syst, Div Nephrol, Los Angeles, CA USA. [Kraut, Jeffrey A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Kraut, JA (reprint author), VHAGLA Healthcare Syst, Div Nephrol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jkraut@ucla.edu NR 62 TC 4 Z9 4 U1 3 U2 14 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1556-3650 EI 1556-9519 J9 CLIN TOXICOL JI Clin. Toxicol. PD AUG PY 2015 VL 53 IS 7 BP 589 EP 595 DI 10.3109/15563650.2015.1056880 PG 7 WC Toxicology SC Toxicology GA CP4WN UT WOS:000359883400001 PM 26114345 ER PT J AU Kaunitz, JD AF Kaunitz, Jonathan D. TI The Discovery of PCR: ProCuRement of Divine Power SO DIGESTIVE DISEASES AND SCIENCES LA English DT Editorial Material C1 [Kaunitz, Jonathan D.] W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. [Kaunitz, Jonathan D.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Kaunitz, JD (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jake@ucla.edu FU NIDDK NIH HHS [P30 DK041301, R01 DK054221] NR 5 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD AUG PY 2015 VL 60 IS 8 BP 2230 EP 2231 DI 10.1007/s10620-015-3747-0 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CP6LF UT WOS:000359998000007 PM 26077976 ER PT J AU Feeney, ER Chung, RT AF Feeney, Eoin R. Chung, Raymond T. TI The Polymerase Chain Reaction: Essential for the Development of Curative Therapy for Hepatitis C SO DIGESTIVE DISEASES AND SCIENCES LA English DT Editorial Material ID GENOTYPE 1 INFECTION; VIRUS LIFE-CYCLE; NON-B-HEPATITIS; NON-A; NS5A INHIBITOR; RNA; HCV; REPLICATION; INTERFERON; CLEARANCE C1 [Feeney, Eoin R.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Feeney, Eoin R.] Univ Coll Dublin, HIV Mol Res Grp, Dublin 2, Ireland. [Chung, Raymond T.] Massachusetts Gen Hosp, Liver Ctr & Div Gastroenterol, Boston, MA 02114 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Liver Ctr & Div Gastroenterol, Boston, MA 02114 USA. EM RTCHUNG@partners.org RI Borges Padilha Ferreira, Fabiana/H-6597-2016; Beletini, Lucimara Fatima/H-6083-2016; Cristina Ferreira, Erika /H-6607-2016; Acorsi, Rayanne/H-6066-2016; Lopes Lera, Daniele/H-6081-2016; Vieira Teixeira, Jorge Juarez/H-6495-2016; MOREIRA NETO, LUIZ JORGE/H-6588-2016; OLIVEIRA, WELLINGTON/H-6591-2016; Botelho, Erlen/H-6594-2016; Moreno, Gustavo/H-6595-2016 OI MOREIRA NETO, LUIZ JORGE/0000-0002-7407-4120; FU NIDDK NIH HHS [K24 DK078772] NR 36 TC 0 Z9 0 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD AUG PY 2015 VL 60 IS 8 BP 2232 EP 2235 DI 10.1007/s10620-015-3748-z PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CP6LF UT WOS:000359998000008 PM 26072321 ER PT J AU Corey, KE Misdraji, J Gelrud, L King, LY Zheng, H Malhotra, A Chung, RT AF Corey, Kathleen E. Misdraji, Joseph Gelrud, Lou King, Lindsay Y. Zheng, Hui Malhotra, Atul Chung, Raymond T. TI Obstructive Sleep Apnea Is Associated with Nonalcoholic Steatohepatitis and Advanced Liver Histology SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Obstructive sleep apnea; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Fibrosis ID CHRONIC INTERMITTENT HYPOXIA; MORBIDLY OBESE-PATIENTS; AIRWAY PRESSURE TREATMENT; FATTY LIVER; SCORING SYSTEM; RISK-FACTORS; DISEASE; INJURY; METAANALYSIS; ENZYMES AB Background and Aims Nonalcoholic fatty liver disease (NAFLD) and obstructive sleep apnea (OSA) are growing in prevalence in the USA. Existing data on the relationship between OSA and NAFLD are conflicting and limited by the use of various histologic definitions of nonalcoholic steatohepatitis (NASH). Using a robust definition of NASH in a large, well-characterized cohort, we sought to evaluate whether OSA was associated with NASH and advanced fibrosis. Methods Two hundred and thirteen subjects undergoing weight loss surgery were queried for OSA and then underwent liver biopsy. NASH was defined, as recommended by the American Association for the Study of Liver Disease, by the presence of all of the following: >5 % macrovesicular steatosis, lobular inflammation, and hepatocyte ballooning. NAFLD activity score (NAS) was also determined for each subject. Results Subjects with OSA had significantly higher alanine and aspartate aminotransferase levels than subjects without OSA (ALT 54.1 vs. 37.7 U/L, P = 0.0007; AST 31.7 vs. 20.5 U/L, P = 0.0007). OSA was associated with the presence of NASH, and this remained significant after adjusting for age, gender, race, and diabetes mellitus (P = 0.03 OR 2.01; 95 %, 1.05-3.87). Steatosis grade, lobular inflammation grade, NAS score, and fibrosis stage were all significantly associated with the presence of OSA and remained so after adjustment. Conclusions OSA is associated with elevated aminotransferase levels, the presence of NASH, and advanced NASH histology. Further studies are needed to evaluate the impact of OSA treatment on NASH. C1 [Corey, Kathleen E.; King, Lindsay Y.; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Misdraji, Joseph] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Gelrud, Lou] Bon Secours Richmond Hlth Syst, Dept Internal Med, Richmond, VA USA. [Zheng, Hui] Massachusetts Gen Hosp, MGH Biostat Ctr, Boston, MA 02114 USA. [Malhotra, Atul] Univ Calif San Diego, Dept Pulm & Crit Care Med, San Diego, CA 92103 USA. [Corey, Kathleen E.; Misdraji, Joseph; Zheng, Hui; Chung, Raymond T.] Harvard Univ, Sch Med, Boston, MA USA. RP Corey, KE (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Warren 1007,55 Fruit St, Boston, MA 02114 USA. EM kcorey@partners.org FU NIH [K23 DK099422, K24 DK078772, K24 HL 093218] FX NIH K23 DK099422 (KEC); K24 DK078772 (RTC); K24 HL 093218 (AM). NR 30 TC 7 Z9 7 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD AUG PY 2015 VL 60 IS 8 BP 2523 EP 2528 DI 10.1007/s10620-015-3650-8 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CP6LF UT WOS:000359998000044 PM 25840922 ER PT J AU Jowett, N Hadlock, TA AF Jowett, Nate Hadlock, Tessa A. TI An Evidence-Based Approach to Facial Reanimation SO FACIAL PLASTIC SURGERY CLINICS OF NORTH AMERICA LA English DT Article DE Facial palsy; Facial paralysis; Facial reanimation; Evidence-based medicine; Synkinesis ID RAT SCIATIC-NERVE; CLINICAL-PRACTICE GUIDELINE; DEPRESSOR MUSCLE MECHANISM; FLACCIDLY PARALYZED FACE; TEMPORAL BONE-FRACTURES; RAMSAY-HUNT-SYNDROME; ACUTE OTITIS-MEDIA; FIBRIN GLUE; BELLS-PALSY; LYME-DISEASE AB This article provides an overview of the current state of the art of facial reanimation using the best available evidence. Medical, surgical, and physical therapy options in acute and long-standing facial palsy are discussed. C1 [Jowett, Nate; Hadlock, Tessa A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, Sch Med,Dept Otolaryngol,Facial Nerve Ctr, Boston, MA 02114 USA. RP Jowett, N (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, Sch Med,Dept Otolaryngol,Facial Nerve Ctr, 243 Charles St, Boston, MA 02114 USA. EM nathan_jowett@meei.harvard.edu NR 149 TC 5 Z9 5 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1064-7406 J9 FACIAL PLAST SURG CL JI Facial Plast. Surg. Clin. N. Am. PD AUG PY 2015 VL 23 IS 3 BP 313 EP + DI 10.1016/j.fsc.2015.04.005 PG 23 WC Surgery SC Surgery GA CP4XQ UT WOS:000359886300006 PM 26208770 ER PT J AU Shaye, D Liu, CC Tollefson, TT AF Shaye, David Liu, C. Carrie Tollefson, Travis T. TI Cleft Lip and Palate An Evidence-Based Review SO FACIAL PLASTIC SURGERY CLINICS OF NORTH AMERICA LA English DT Review DE Cleft lip; Cleft palate; Evidence-based medicine; Outcomes ID COMPLETE UNILATERAL CLEFT; DENTAL ARCH RELATIONSHIPS; EARLY MAXILLARY GROWTH; DELAYED HARD PALATE; OPPOSING Z-PLASTY; NASAL DEFORMITY; VELOPHARYNGEAL INSUFFICIENCY; INTRAVELAR VELOPLASTY; PHARYNGEAL FLAP; PRIMARY REPAIR AB The current article reviews the pertinent literature on the management of cleft lip and palate. We review the commonly used surgical techniques for repair, adjunctive options for treatment, clinical outcomes, complications, and concerns to consider. Throughout the discussion, we state the level of evidence where applicable and identify areas for future study. C1 [Shaye, David] Harvard Univ, Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, Sch Med, Boston, MA 02114 USA. [Liu, C. Carrie] Univ Calgary, Foothills Med Ctr, Dept Surg, Div Otolaryngol Head & Neck Surg, Calgary, AB T2N 2T9, Canada. [Tollefson, Travis T.] Univ Calif Davis, Dept Otolaryngol Head & Neck Surg, Facial Plast & Reconstruct Surg, Sacramento, CA 95817 USA. RP Tollefson, TT (reprint author), Univ Calif Davis, Dept Otolaryngol Head & Neck Surg, Facial Plast & Reconstruct Surg, 2521 Stockton Blvd,Suite 7200, Sacramento, CA 95817 USA. EM travis.tollefson@ucdmc.ucdavis.edu OI Tollefson, Travis/0000-0002-8658-8647 NR 133 TC 1 Z9 1 U1 4 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1064-7406 J9 FACIAL PLAST SURG CL JI Facial Plast. Surg. Clin. N. Am. PD AUG PY 2015 VL 23 IS 3 BP 357 EP + DI 10.1016/j.fsc.2015.04.008 PG 17 WC Surgery SC Surgery GA CP4XQ UT WOS:000359886300009 PM 26208773 ER PT J AU Joly, JM Lloyd, SG AF Joly, Joanna M. Lloyd, Steven G. TI Imaging in patients with advanced therapies for heart failure SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Editorial Material ID CARDIAC ALLOGRAFT VASCULOPATHY; TRANSPLANT; TOMOGRAPHY C1 [Joly, Joanna M.; Lloyd, Steven G.] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Lloyd, Steven G.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Lloyd, SG (reprint author), Cardiovasc MRI, D-101,1808 7th Ave South, Birmingham, AL 35294 USA. EM sglloyd@uab.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 1071-3581 EI 1532-6551 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD AUG PY 2015 VL 22 IS 4 BP 639 EP 642 DI 10.1007/s12350-015-0111-x PG 4 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CP5QE UT WOS:000359937800006 PM 25824016 ER PT J AU Hage, FG AlJaroudi, WA AF Hage, Fadi G. AlJaroudi, Wael A. TI Review of cardiovascular imaging in The Journal of Nuclear Cardiology in 2014: Part 2 of 2: Myocardial perfusion imaging SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Review DE Myocardial perfusion imaging; SPECT; phase analysis; dyssynchrony; appropriateness; safety; regadenoson ID VENTRICULAR MECHANICAL DYSSYNCHRONY; CORONARY-ARTERY-DISEASE; PROGNOSTIC VALUE; GATED SPECT; COMPUTED-TOMOGRAPHY; DIABETIC-PATIENTS; PHASE-ANALYSIS; HEART-FAILURE; REGADENOSON; STRESS AB In this new feature of The Journal of Nuclear Cardiology we will summarize key articles that were published in the Journal in the previous year. In the first article of this 2-part series we concentrated on publications dealing with cardiac positron emission tomography, computed tomography, and neuronal imaging. This review will focus on myocardial perfusion imaging summarizing advances in the field including in diagnosis, prognosis, appropriateness, and safety of testing. C1 [Hage, Fadi G.] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Cardiol Sect, Birmingham, AL USA. [AlJaroudi, Wael A.] Amer Univ Beirut, Div Cardiovasc Med Cardiovasc Imaging, Med Ctr, Beirut, Lebanon. RP Hage, FG (reprint author), Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. EM fadihage@uab.edu; wa53@aub.edu.lb OI Hage, Fadi/0000-0002-1397-4942 FU Astellas Pharma US FX Dr. Hage has received grant support from Astellas Pharma US. NR 32 TC 3 Z9 3 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 EI 1532-6551 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD AUG PY 2015 VL 22 IS 4 BP 714 EP 719 DI 10.1007/s12350-015-0144-1 PG 6 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CP5QE UT WOS:000359937800016 PM 25920482 ER PT J AU Farag, AA Hage, FG AF Farag, Ayman A. Hage, Fadi G. TI Incidentally found giant thymomas by SPECT myocardial perfusion imaging (vol 22, pg 385, 2015) SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Correction C1 [Farag, Ayman A.; Hage, Fadi G.] Univ Alabama Birmingham, Div Cardiovasc Dis, Dept Med, Birmingham, AL 35294 USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Cardiol Sect, Birmingham, AL USA. RP Farag, AA (reprint author), Univ Alabama Birmingham, Div Cardiovasc Dis, Dept Med, THT 311,1900 Univ Blvd, Birmingham, AL 35294 USA. EM afarag@uab.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 EI 1532-6551 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD AUG PY 2015 VL 22 IS 4 BP 786 EP 786 DI 10.1007/s12350-015-0189-1 PG 1 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CP5QE UT WOS:000359937800023 PM 26058351 ER PT J AU Garcia, MJ Blankstein, R Budoff, MJ Dent, JM Drachman, DE Lesser, JR Grover-McKay, M Schussler, JM Voros, S Wann, LS AF Garcia, Mario J. Blankstein, Ron Budoff, Matthew J. Dent, John M. Drachman, Douglas E. Lesser, John R. Grover-McKay, Maleah Schussler, Jeffrey M. Voros, Szilard Wann, L. Samuel TI COCATS 4 Task Force 7: Training in Cardiovascular Computed Tomographic Imaging Endorsed by the American Society of Nuclear Cardiology, Society for Cardiovascular Angiography and Interventions, Society of Atherosclerosis Imaging and Prevention, and the Society of Cardiovascular Computed Tomography SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article ID STATEMENT; COMPETENCE C1 [Garcia, Mario J.] Montefiore Med Ctr, Albert Einstein Coll Med, Cardiol, Bronx, NY 10467 USA. [Garcia, Mario J.] Montefiore Med Ctr, Albert Einstein Coll Med, Med & Radiol, Bronx, NY 10467 USA. [Blankstein, Ron] Brigham & Womens Hosp, Cardiac CT, Boston, MA 02115 USA. [Blankstein, Ron] Brigham & Womens Hosp, Cardiovasc Imaging Training Program, Boston, MA 02115 USA. [Blankstein, Ron] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Blankstein, Ron] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Blankstein, Ron] Harvard Univ, Sch Med, Med & Radiol, Cambridge, MA 02138 USA. [Budoff, Matthew J.] Los Angeles Biomed Res Inst, Div Cardiol, Los Angeles, CA USA. [Dent, John M.] Univ Virginia Hlth Syst, Dept Med, Med Cardiol, Charlottesville, VA USA. [Drachman, Douglas E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Lesser, John R.] Minneapolis Heart Inst, Cardiovasc CT & MRI, Minneapolis, MN USA. [Grover-McKay, Maleah] DaVita Healthcare Partners, Plaza Cardiol, Denver, CO USA. [Schussler, Jeffrey M.] Baylor Univ, Med Ctr, CardiovascularICU, Waco, TX 76798 USA. [Schussler, Jeffrey M.] Texas A&M Coll Med, Med, Bryan, TX USA. [Voros, Szilard] SUNY Stony Brook, Med Ctr, Radiol & Med Cardiol, Stony Brook, NY USA. [Wann, L. Samuel] Univ Wisconsin, Madison, WI 53706 USA. [Wann, L. Samuel] Med Coll Wisconsin, Med, Milwaukee, WI 53226 USA. RP Garcia, MJ (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, Cardiol, Bronx, NY 10467 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 EI 1532-6551 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD AUG PY 2015 VL 22 IS 4 BP 826 EP 839 DI 10.1007/s12350-015-0163-y PG 14 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CP5QE UT WOS:000359937800029 PM 26134884 ER PT J AU Loggia, ML Berna, C Kim, J Cahalan, CM Martel, MO Gollub, RL Wasan, AD Napadow, V Edwards, RR AF Loggia, Marco L. Berna, Chantal Kim, Jieun Cahalan, Christine M. Martel, Marc-Olivier Gollub, Randy L. Wasan, Ajay D. Napadow, Vitaly Edwards, Robert R. TI The Lateral Prefrontal Cortex Mediates the Hyperalgesic Effects of Negative Cognitions in Chronic Pain Patients SO JOURNAL OF PAIN LA English DT Article DE Fibromyalgia; catastrophizing; negative affect; functional magnetic resonance imaging; psychophysics ID DEEP-TISSUE PAIN; CATASTROPHIZING SCALE; FIBROMYALGIA SYNDROME; PRESSURE ALGOMETRY; NEURAL RESPONSES; PERCEPTION; CONNECTIVITY; ANALGESIA; PLACEBO; HUMANS AB Although high levels of negative affect and cognitions have been associated with greater pain sensitivity in chronic pain conditions, the neural mechanisms mediating the hyperalgesic effect of psychological factors in patients with pain disorders are largely unknown. In this cross-sectional study, we hypothesized that 1) catastrophizing modulates brain responses to pain anticipation and 2) anticipatory brain activity mediates the hyperalgesic effect of different levels of catastrophizing in fibromyalgia (FM) patients. Using functional magnetic resonance imaging, we scanned the brains of 31 FM patients exposed to visual cues anticipating the onset of moderately intense deep-tissue pain stimuli. Our results indicated the existence of a negative association between catastrophizing and pain-anticipatory brain activity, including in the right lateral prefrontal cortex. A bootstrapped mediation analysis revealed that pain-anticipatory activity in the lateral prefrontal cortex mediates the association between catastrophizing and pain sensitivity. These findings highlight the role of the lateral prefrontal cortex in the pathophysiology of FM-related hyperalgesia and suggest that deficits in the recruitment of pain-inhibitory brain circuitry during pain-anticipatory periods may play an important contributory role in the association between various degrees of widespread hyperalgesia in FM and levels of catastrophizing, a well-validated measure of negative cognitions and psychological distress. Perspective: This article highlights the presence of alterations in pain-anticipatory brain activity in FM. These findings provide the rationale for the development of psychological or neuro feedback-based techniques aimed at modifying patients' negative affect and cognitions toward pain. (C) 2015 by the American Pain Society C1 [Loggia, Marco L.; Kim, Jieun; Gollub, Randy L.; Napadow, Vitaly] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,MIT, Charlestown, MA USA. [Loggia, Marco L.; Cahalan, Christine M.; Martel, Marc-Olivier; Wasan, Ajay D.; Napadow, Vitaly; Edwards, Robert R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesiol Perioperat & Pain Med, Chestnut Hill, MA USA. [Berna, Chantal] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Gollub, Randy L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA USA. [Wasan, Ajay D.] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA 15261 USA. [Wasan, Ajay D.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15261 USA. [Napadow, Vitaly] Kyung Hee Univ, Dept Biomed Engn, Yongin, South Korea. RP Loggia, ML (reprint author), Massachusetts Gen Hosp, Bldg 149,Suite 2301, Charlestown, MA 02129 USA. EM marco@nmr.mgh.harvard.edu OI Loggia, Marco/0000-0002-8026-5265 FU National Institutes of Health (NIH) [R01-AR064367, R01-AT004714, P01-AT002048, P01-AT006663, R01-AT005280, R01-AG034982, R21-AR057920, K23DA20681]; National Institute of Biomedical Imaging and Bioengineering (NIBIB), NIH [P41EB015896]; NIH [S10-RR021110, S10RR023401, S10-RR023043] FX This research was supported by the following National Institutes of Health (NIH) grants (R01-AR064367, R01-AT004714, P01-AT002048, P01-AT006663, R01-AT005280, R01-AG034982, R21-AR057920, K23DA20681), and was carried out in part at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41EB015896, a P41 Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), NIH. This work also involved the use of instrumentation supported by the NIH Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program; specifically, grant numbers S10-RR021110, S10RR023401, and S10-RR023043. NR 53 TC 6 Z9 6 U1 1 U2 9 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD AUG PY 2015 VL 16 IS 8 BP 692 EP 699 DI 10.1016/j.jpain.2015.04.003 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CP5AK UT WOS:000359893500002 PM 25937162 ER PT J AU Provenzale, D Jasperson, K Ahnen, DJ Aslanian, H Bray, T Cannon, JA David, DS Early, DS Erwin, D Ford, JM Giardiello, FM Gupta, S Halverson, AL Hamilton, SR Hampel, H Ismail, MK Klapman, JB Larson, DW Lazenby, AJ Lynch, PM Mayer, RJ Ness, RM Rao, MS Regenbogen, SE Shike, M Steinbach, G Weinberg, D Dwyer, MA Freedman-Cass, DA Darlow, S AF Provenzale, Dawn Jasperson, Kory Ahnen, Dennis J. Aslanian, Harry Bray, Travis Cannon, Jamie A. David, Donald S. Early, Dayna S. Erwin, Deborah Ford, James M. Giardiello, Francis M. Gupta, Samir Halverson, Amy L. Hamilton, Stanley R. Hampel, Heather Ismail, Mohammad K. Klapman, Jason B. Larson, David W. Lazenby, Audrey J. Lynch, Patrick M. Mayer, Robert J. Ness, Reid M. Rao, M. Sambasiva Regenbogen, Scott E. Shike, Moshe Steinbach, Gideon Weinberg, David Dwyer, Mary A. Freedman-Cass, Deborah A. Darlow, Susan TI Colorectal Cancer Screening, Version 1.2015 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; DOSE POLYETHYLENE-GLYCOL; FECAL-OCCULT-BLOOD; SERVICES TASK-FORCE; FAMILY-HISTORY; STOOL DNA; COLONOSCOPIC POLYPECTOMY; AFTERNOON COLONOSCOPY; ADENOMATOUS POLYPS; AMERICAN-COLLEGE AB The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colorectal Cancer Screening provide recommendations for selecting individuals for colorectal cancer screening, and for evaluation and follow-up of colon polyps. These NCCN Guidelines Insights summarize major discussion points of the 2015 NCCN Colorectal Cancer Screening panel meeting. Major discussion topics this year were the state of evidence for CT colonography and stool DNA testing, bowel preparation procedures for colonoscopy, and guidelines for patients with a positive family history of colorectal cancer. C1 [Provenzale, Dawn] Duke Canc Inst, Durham, NC USA. [Jasperson, Kory] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Ahnen, Dennis J.] Univ Colorado, Canc Ctr, Boulder, CO 80309 USA. [Aslanian, Harry] Smilow Canc Hosp, Yale Canc Ctr, New Haven, CT USA. [Bray, Travis] Hereditary Colon Canc Fdn, Park City, UT USA. [Cannon, Jamie A.] Univ Alabama, Birmingham Comprehens Canc Ctr, Tuscaloosa, AL 35487 USA. [David, Donald S.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Early, Dayna S.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Early, Dayna S.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Erwin, Deborah] Roswell Pk Canc Inst, Buffalo, NY USA. [Ford, James M.] Stanford Canc Inst, Palo Alto, CA USA. [Giardiello, Francis M.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Gupta, Samir] UC San Diego Moores Canc Ctr, San Diego, CA USA. [Halverson, Amy L.; Regenbogen, Scott E.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Hamilton, Stanley R.; Lynch, Patrick M.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Hampel, Heather] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Hampel, Heather] Solove Res Inst, Columbus, OH USA. [Ismail, Mohammad K.] Univ Tennessee, St Jude Childrens Res Hosp, Hlth Sci Ctr, Knoxville, TN 37996 USA. [Klapman, Jason B.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Larson, David W.] Mayo Clin, Ctr Canc, Rochester, MN USA. [Lazenby, Audrey J.] Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Mayer, Robert J.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Ness, Reid M.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Regenbogen, Scott E.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Shike, Moshe] Mem Sloan Kettering Canc Ctr, Brooklyn, NY USA. [Steinbach, Gideon] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA USA. [Weinberg, David] Fox Chase Canc Ctr, Philadelphia, PA USA. RP Provenzale, D (reprint author), Duke Canc Inst, Durham, NC USA. FU Eisai; Bristol-Myers Squibb; Genentech BioOncology; Merck; Novartis Oncology; Novocure; Boehringer Ingelheim Pharmaceuticals, Inc. FX Supported by an educational grant from Eisai; a contribution from Exelixis Inc.; educational grants from Bristol-Myers Squibb, Genentech BioOncology, Merck, Novartis Oncology, Novocure; and by an independent educational grant from Boehringer Ingelheim Pharmaceuticals, Inc. NR 63 TC 14 Z9 17 U1 2 U2 6 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD AUG PY 2015 VL 13 IS 8 BP 959 EP 968 PG 10 WC Oncology SC Oncology GA CO9CO UT WOS:000359470200006 PM 26285241 ER PT J AU Berger, AM Mooney, K Alvarez-Perez, A Breitbart, WS Carpenter, KM Cella, D Cleeland, C Dotan, E Eisenberger, MA Escalante, CP Jacobsen, PB Jankowski, C LeBlanc, T Ligibel, JA Loggers, ET Mandrell, B Murphy, BA Palesh, O Pirl, WF Plaxe, SC Riba, MB Rugo, HS Salvador, C Wagner, LI Wagner-Johnston, ND Zachariah, FJ Bergman, MA Smith, C AF Berger, Ann M. Mooney, Kathi Alvarez-Perez, Amy Breitbart, William S. Carpenter, Kristen M. Cella, David Cleeland, Charles Dotan, Efrat Eisenberger, Mario A. Escalante, Carmen P. Jacobsen, Paul B. Jankowski, Catherine LeBlanc, Thomas Ligibel, Jennifer A. Loggers, Elizabeth Trice Mandrell, Belinda Murphy, Barbara A. Palesh, Oxana Pirl, William F. Plaxe, Steven C. Riba, Michelle B. Rugo, Hope S. Salvador, Carolina Wagner, Lynne I. Wagner-Johnston, Nina D. Zachariah, Finly J. Bergman, Mary Anne Smith, Courtney TI Cancer-Related Fatigue, Version 2.2015 SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; BONE-MARROW-TRANSPLANTATION; PLACEBO-CONTROLLED TRIAL; LONG-TERM SURVIVORS; DOUBLE-BLIND TRIAL; PATIENT-CONTROLLED METHYLPHENIDATE; PATIENTS RECEIVING CHEMOTHERAPY; ANDROGEN-DEPRIVATION THERAPY; COGNITIVE-BEHAVIORAL THERAPY AB Cancer-related fatigue is defined as a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning. It is one of the most common side effects in patients with cancer. Fatigue has been shown to be a consequence of active treatment, but it may also persist into posttreatment periods. Furthermore, difficulties in end-of-life care can be compounded by fatigue. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cancer-Related Fatigue provide guidance on screening for fatigue and recommendations for interventions based on the stage of treatment. Interventions may include education and counseling, general strategies for the management of fatigue, and specific nonpharmacologic and pharmacologic interventions. Fatigue is a frequently underreported complication in patients with cancer and, when reported, is responsible for reduced quality of life. Therefore, routine screening to identify fatigue is an important component in improving the quality of life for patients living with cancer. C1 [Berger, Ann M.] Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Mooney, Kathi] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Alvarez-Perez, Amy] Roswell Pk Canc Inst, Buffalo, NY USA. [Breitbart, William S.] Mem Sloan Kettering Canc Ctr, Brooklyn, NY USA. [Carpenter, Kristen M.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp & Solove Res Inst, Columbus, OH 43210 USA. [Cella, David] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Cleeland, Charles; Escalante, Carmen P.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Dotan, Efrat] Fox Chase Canc Ctr, Philadelphia, PA USA. [Eisenberger, Mario A.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Jacobsen, Paul B.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Jankowski, Catherine] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [LeBlanc, Thomas] Duke Canc Inst, Durham, NC USA. [Ligibel, Jennifer A.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Loggers, Elizabeth Trice] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA USA. [Mandrell, Belinda] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Murphy, Barbara A.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Palesh, Oxana] Stanford Canc Inst, Palo Alto, CA USA. [Pirl, William F.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Plaxe, Steven C.] UC San Diego Moores Canc Ctr, San Diego, CA USA. [Riba, Michelle B.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Rugo, Hope S.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Salvador, Carolina] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Wagner, Lynne I.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Wagner-Johnston, Nina D.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Wagner-Johnston, Nina D.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Zachariah, Finly J.] City Hope Comprehens Canc Ctr, Duarte, CA USA. RP Berger, AM (reprint author), Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. OI LeBlanc, Thomas/0000-0002-0546-7895 NR 217 TC 21 Z9 21 U1 4 U2 16 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD AUG PY 2015 VL 13 IS 8 BP 1012 EP 1039 PG 28 WC Oncology SC Oncology GA CO9CO UT WOS:000359470200012 PM 26285247 ER PT J AU Monteith, LL Menefee, DS Forster, JE Wanner, JL Bahraini, NH AF Monteith, Lindsey L. Menefee, Deleene S. Forster, Jeri E. Wanner, Jill L. Bahraini, Nazanin H. TI Sexual Trauma and Combat During Deployment: Associations With Suicidal Ideation Among OEF/OIF/OND Veterans SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID MENTAL-HEALTH; GENDER-DIFFERENCES; RESILIENCE INVENTORY; MILITARY PERSONNEL; AFGHANISTAN; RISK; IRAQ; ASSAULT; SAMPLE; EXPERIENCES AB Compelling evidence has emerged on the association between military sexual trauma and suicide attempt; however, research investigating how sexual trauma during deployment relates to suicidal ideation has received considerably less attention and has yielded mixed findings. Furthermore, such research has not accounted for other types of trauma that may occur during deployment. Our objectives were to examine whether sexual trauma during deployment was associated with recent suicidal ideation, adjusting for exposure to combat. Our sample included 199 Operation Enduring Freedom/Iraqi Freedom/New Dawn (OEF/OIF/OND) veterans entering inpatient trauma-focused treatment who completed the Beck Scale for Suicide Ideation (Beck & Steer, ) and the Deployment Risk and Resilience Inventory Sexual Harassment and Combat Experiences Scales (King, King, Vogt, Knight, & Samper, ). Deployment-related sexual trauma was significantly associated with recent suicidal ideation, adjusting for age and gender ( = .18, (2)(p) = .03) and additionally for combat ( = .17, (2)(p) = .02). These findings underscore the importance of assessing for deployment-related sexual trauma when assessing suicide risk in OEF/OIF/OND veterans in inpatient settings. Resumen Trauma Sexual, Combate e Ideacion Suicida Evidencia convincente ha surgido sobre la asociacion entre trauma sexual militar e intento suicida; sin embargo, la investigacion de como el trauma sexual durante el despliegue se relaciona con la ideacion suicida ha recibido considerablemente menos atencion y ha arrojado resultados mixtos. Ademas, tal investigacion no ha dado cuenta de otros tipos de trauma que pueden ocurrir durante el despliegue. Nuestros objetivos fueron investigar si el trauma sexual durante el despliegue estaba asociado a ideacion suicida reciente, ajustando por exposicion a combate. Nuestra mezcla incluyo 199 veteranos OEF/OIF/OND hospitalizados para tratamiento focalizado en el trauma, que completaron la Escala de Beck para Ideacion Suicida, el Inventario de Riesgo de Despliegue y Resiliencia, y las escalas de Acoso Sexual y de Experiencias de Combate. El trauma asociado a despliegue se asocio en forma significativa a ideacion suicida reciente, ajustando por edad y genero ( = .18, p 2 = .03) y adicionalmente por combate ( = .17, p 2 = .02). Estos hallazgos subrayan la importancia de considerar el trauma asociado a despliegue al evaluar riesgo suicida en veteranos OEF/OIF/OND en contexto de hospitalizacion. Traditional and Simplified Chinese Abstracts by AsianSTSS ?? : OEF/OIF/OND????,???????????????????? ??: ?????????????????????,?????????????????????????,?????????;?????????????????????????????????????,??????????????????????????199?????????????OEF/OIF/OND????,????????????????????????????????????????????( = .18, p(2) = .03),???????????( = .17, p(2) = .02)?,?????????????????????????????,????OEF/OIF/OND??????????,????????????????? ?? : OEF/OIF/OND????,??????????????????? ??: ?????????????????????,?????????????????????????,?????????;????????????????????????????????????,??????????????????????????199?????????????OEF/OIF/OND????,???????????????????????????????????????????( = .18, p(2) = .03),??????????( = .17, p(2) = .02)?,?????????????????????????????,????OEF/OIF/OND??????????,????????????????? C1 [Monteith, Lindsey L.; Forster, Jeri E.; Bahraini, Nazanin H.] Denver VA Med Ctr, VISN MIRECC 19, Denver, CO 80220 USA. [Monteith, Lindsey L.; Bahraini, Nazanin H.] Univ Colorado, Dept Psychiat, Aurora, CO USA. [Menefee, Deleene S.; Wanner, Jill L.] Michael E DeBakey VA Med Ctr, VISN MIRECC 19, Houston, CO USA. [Menefee, Deleene S.; Wanner, Jill L.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Forster, Jeri E.] Colorado Sch Publ Hlth, Dept Biostat & Informat, Aurora, CO USA. [Bahraini, Nazanin H.] Univ Colorado, Dept Phys Med & Rehabil, Aurora, CO USA. RP Monteith, LL (reprint author), Denver VA Med Ctr, VISN MIRECC 19, 1055 Clermont St, Denver, CO 80220 USA. EM lindsey.monteith@va.gov NR 28 TC 2 Z9 2 U1 2 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD AUG PY 2015 VL 28 IS 4 BP 283 EP 288 DI 10.1002/jts.22018 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CP5HR UT WOS:000359912400003 PM 26190530 ER PT J AU Millegan, J Milburn, EK LeardMann, CA Street, AE Williams, D Trone, DW Crum-Cianflone, NF AF Millegan, Jeffrey Milburn, Emma K. LeardMann, Cynthia A. Street, Amy E. Williams, Diane Trone, Daniel W. Crum-Cianflone, Nancy F. TI Recent Sexual Trauma and Adverse Health and Occupational Outcomes Among US Service Women SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID ASSAULT HISTORY; MILLENNIUM COHORT; GENERAL-POPULATION; VETERANS-HEALTH; MILITARY PERSONNEL; HARASSMENT; GENDER; CARE; METAANALYSIS; AFGHANISTAN AB Sexual trauma is prevalent among military women, but data on potential effects are needed. The association of sexual trauma with health and occupational outcomes was investigated using longitudinal data from the Millennium Cohort Study. Of 13,001 U.S. service women, 1,364 (10.5%) reported recent sexual harassment and 374 (2.9%) recent sexual assault. Women reporting recent sexual harassment or assault were more likely to report poorer mental health: OR = 1.96, 95% CI [1.71, 2.25], and OR = 3.45, 95% CI [2.67, 4.44], respectively. They reported poorer physical health: OR = 1.39, 95% CI [1.20, 1.62], and OR = 1.39, 95% CI [1.04, 1.85], respectively. They reported difficulties in work/activities due to emotional health: OR = 1.80, 95% CI [1.59, 2.04], and OR = 2.70, 95% CI [2.12, 3.44], respectively. They also reported difficulties with physical health: OR = 1.55, 95% CI [1.37, 1.75], and OR = 1.52 95% CI [1.20, 1.91], respectively, after adjustment for demographic, military, health, and prior sexual trauma characteristics. Recent sexual harassment was associated with demotion, OR = 1.47, 95% CI [1.12, 1.93]. Findings demonstrated that sexual trauma represents a potential threat to military operational readiness and draws attention to the importance of prevention strategies and services to reduce the burden of sexual trauma on military victims. Resumen Salud de las mujeres militares y vida laboral post trauma sexual El trauma sexual es prevalente entre las mujeres militares, pero se necesita informacion acerca de sus potenciales efectos. Se investigo la asociacion de trauma sexual con sus consecuencias laborales y en la salud, usando datos longitudinales del Estudio de Cohorte Millenium. De 1.300 mujeres norteamericanas en servicio, 1.364 (10.5%) reporto acoso sexual reciente y 374 (2.9%) abuso sexual reciente. Las mujeres que reportaron acoso sexual o abuso reciente fueron las que con mayor probabilidad reportaron salud mental mas deteriorada (OR = 1.96 95% CI [1.71, 2.25]; y OR = 3.45 95% CI [2.67,4.44], respectivamente), Salud fisica mas deteriorada(OR = 1.39 95% CI [1.20,1.62], y OR = 1.39 95% CI [1.04, 1.85], respectivamente), y dificultades en el trabajo/ actividades debido a la Salud emocional (OR = 1.80 95% CI [1.59, 2.04]; y OR = 2.70 95% CI [2.12-3.44], respectivamente) despues del ajuste por caracteristicas demograficas, militares, salud y trauma sexual previo. El acoso sexual reciente se asocio con descenso de categoria (OR = 1.47 95% CI [1.12, 1.93]. Los hallazgos demuestran que el trauma sexual representa una amenaza potencial para la preparacion operacion militar y llama la atencion sobre la importancia de las estrategias y los servicios de prevencion para reducir la carga de trauma sexual en victimas militares. Traditional and Simplified Chinese Abstracts by AsianSTSS ?? : ???????????????????????? ??: ??????????,??????????????????????????????????,??????????????????13,001??????,1,364?(10.5%)???????,374?(2.9%)????????????????????????????????,??????????????????,?????????????(??? OR = 1.96 95% CI [1.71, 2.25] ? OR = 3.45 95% CI [2.67, 4.44])????????(??? OR = 1.39 95% CI [1.20, 1.62] ? OR = 1.39 95% CI [1.04, 1.85]),??????????(??? OR = 1.80 95% CI [1.59, 2.04] ? OR = 2.70 95% CI [2.12-3.44])?????(??? OR = 1.55 95% CI [1.37-1.75] ? OR = 1.52 95% CI [1.20-1.91])????????????????????????(OR = 1.47 95% CI [1.12, 1.93])???????,??????????????????,?????????????????,?????????????? ?? : ???????????????????????? ??: ??????????,??????????????????????????????????,??????????????????13,001??????,1,364?(10.5%)??????,374?(2.9%)??????????????????????????????,??????????????????,?????????????(??? OR = 1.96 95% CI [1.71, 2.25] ? OR = 3.45 95% CI [2.67, 4.44])????????(??? OR = 1.39 95% CI [1.20, 1.62] ? OR = 1.39 95% CI [1.04, 1.85]),??????????(??? OR = 1.80 95% CI [1.59, 2.04] ? OR = 2.70 95% CI [2.12-3.44])?????(??? OR = 1.55 95% CI [1.37-1.75] ? OR = 1.52 95% CI [1.20-1.91])????????????????????????(OR = 1.47 95% CI [1.12, 1.93])???????,??????????????????,?????????????????,?????????????? C1 [Millegan, Jeffrey] US Navy, Hlth Res Ctr, Directorate Mental Hlth, San Diego, CA 92106 USA. [Milburn, Emma K.; LeardMann, Cynthia A.; Trone, Daniel W.; Crum-Cianflone, Nancy F.] US Navy, Hlth Res Ctr, Deployment Hlth Res Dept, San Diego, CA 92106 USA. [Street, Amy E.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Street, Amy E.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Williams, Diane] US Navy, Hlth Res Ctr, Warfighter Performance Dept, San Diego, CA 92106 USA. RP LeardMann, CA (reprint author), US Navy, Hlth Res Ctr, 140 Sylvester Rd, San Diego, CA 92106 USA. EM cynthia.a.leardmann.ctr@mail.mil FU Department of Defense [60002]; Clinical Investigations Department at Naval Medical Center San Diego FX This work represents Report 14-13, supported by the Department of Defense, under Work Unit No. 60002, and through funding by the Clinical Investigations Department at Naval Medical Center San Diego. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of the Army, Department of the Air Force, Department of Defense, Department of Veterans Affairs, or the U.S. Government. Approved for public release; distribution is unlimited. This research was conducted in compliance with all applicable federal regulations governing the protection of human subjects (Protocol NHRC.2000.0007). The funding organization had no role in the design and conduct of the study; collection, analysis, or preparation of data; or preparation, review or approval of the manuscript. In addition to the authors, we thank James Davies; Carrie Donoho, PhD; Isabel Jacobson, MPH; William Lee; Hector Lemus, PhD; Denise Lovec-Jenkins; Gordon Lynch; Jill MacDougall; Anna Nagel, MPH; Christopher Phillips, MD, MPH; Kari Sausedo, MA; Beverly Sheppard; Steven Speigle; Jennifer Walstrom; Martin White, MPH; and James Whitmer; from the Department of Deployment Health Research, Naval Health Research Center, San Diego, California. The authors also thank the professionals from the U.S. Army Medical Research and Materiel Command, especially those from the Military Operational Medicine Research Program, Fort Detrick, MD; Scott L. Seggerman from the Management Information Division, Defense Manpower Data Center, Monterey, CA; and the Millennium Cohort Study participants. NR 32 TC 3 Z9 3 U1 6 U2 17 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 2015 VL 28 IS 4 BP 298 EP 306 DI 10.1002/jts.22028 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CP5HR UT WOS:000359912400005 PM 26201507 ER PT J AU Taft, CT Weatherill, RP Scott, JP Thomas, SA Kang, HK Eckhardt, CI AF Taft, Casey T. Weatherill, Robin P. Scott, Jillian Panuzio Thomas, Sarah A. Kang, Han K. Eckhardt, Christopher I. TI Social Information Processing in Anger Expression and Partner Violence in Returning US Veterans SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; ARTICULATED THOUGHTS; MARITALLY VIOLENT; INTIMATE PARTNER; COMBAT VETERANS; SKILL DEFICITS; AGGRESSION; ABUSE; PERPETRATION; METAANALYSIS AB We examined social information processing factors that could represent pathways through which posttraumatic stress disorder (PTSD) symptoms relate to anger expression and intimate partner violence (IPV) perpetration in returning U.S. veterans. The sample included 92 male Operation Enduring Freedom/Operation Iraqi Freedom veterans, primarily Caucasian (77.4%), with smaller numbers of African American, Asian, Hispanic or Latino, American Indian or Alaskan Native, and other minority participants (9.7%, 2.2%, 2.2%, 3.2%, and 5.3% respectively). The average age was 40.37 (SD = 9.63) years. Data were collected through self-report questionnaires (PTSD Checklist, State-Trait Anger Expression Scale, Revised Conflict Tactics Scales) and the Articulated Thoughts in Simulated Situations experimental protocol. Laboratory-based assessment of cognitive biases and hostile attributions were tested as mediators of associations between PTSD symptoms and anger expression and IPV. Among the PTSD symptom clusters, hyperarousal symptoms were most strongly associated with anger expression (r = .50) and IPV perpetration (r = .27). Cognitive biases mediated associations between PTSD total scores and 3 of 4 PTSD cluster scores as well as anger expression. Hostile attribution biases were also associated with IPV perpetration (r = .23). We discuss the implications of these findings for understanding social information processing mechanisms for the relationship between PTSD symptoms and aggression. Resumen PROCESAMIENTO DE LA INFORMACIN SOCIAL Y AGRESIN Examinamos los factores de procesamiento de la informacion social que podrian representar vias a traves de los cuales los sintomas de trastorno por estres postraumatico (TEPT) se relacionan con la expresion de ira y la perpetracion de violencia intima en la pareja (VIP) en veteranos que vuelven a EEUU. La muestra incluyo 92 hombres veteranos de la Operacion Libertad Duradera/ Operacion de Liberacion Iraqui, primariamente caucasicos (77.4%), con un numero pequeno de americanos de origen africano, asiatico, hispanico o latino, indio americano o nativos de Alaska, y otros participantes minoritarios (9.7%,2.2%,2.2%,3.2% y 5.3% respectivamente). El promedio de edad fue 40.37 (DE = 9.63) anos. Los datos fueron recolectados a traves de cuestionarios autoreportados TEPT lista de verificacion, Escala de Expresion de Ira, Escalas de Tacticas de Conflicto Revisadas) y los Pensamientos Articulados del protocolo experimental de Situaciones Simuladas. Evaluaciones de los sesgos cognitivos y las atribuciones hostiles basadas en Laboratorio fueron probadas como mediadores de asociaciones entre los sintomas de TEPT y expresion de ira y PIV. Entre los grupos de sintomas de TEPT, los sintomas de hiperalerta fueron mas fuertemente asociados con la expresion de ira (r = .50) y perpetracion de PIV (r = .23). Se discuten las implicaciones de estos hallazgos para la comprension de los mecanismos de procesamiento de la informacion social para la relacion entre los sintomas de TEPT y la agresion. Traditional and Simplified Chinese Abstracts by AsianSTSS ?? : ????????????????????? ??: ??????????????????????,??????????????(PTSD)??????????????(IPV)???????????92?????????(OEF)??????????(OIF)??????,??????(77.4%),?????????????????????????????????????,????????(???9.7%, 2.2%, 2.2%, 3.2% ?5.3%)????????40.37?(SD = 9.63) ?????????? (PTSD?????????????????????????)????????????????????????????????????????,????????PTSD????????IPV??????????PTSD????,???????????(r = .50) ?IPV??(r = .27)???????????PTSD????????PTSD???????????????????????????IPV??????(r = .23)?????????????????????????,????PTSD??????????? ? ?? : ????????????????????? ??: ??????????????????????,??????????????(PTSD)??????????????(IPV)???????????92?????????(OEF)??????????(OIF)??????,??????(77.4%),?????????????????????????????????????,????????(???9.7%, 2.2%, 2.2%, 3.2% ? 5.3%)????????40.37?(SD = 9.63) ?????????? (PTSD?????????????????????????)???????????????????????????????????????,????????PTSD????????IPV?????????PTSD????,???????????(r = .50) ?IPV??(r = .27)???????????PTSD????????PTSD??????????????????????????IPV??????(r = .23)??????????????????????????,????PTSD??????????? ? C1 [Taft, Casey T.; Weatherill, Robin P.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Natl Ctr PTSD,Behav Sci Div, Boston, MA 02118 USA. [Taft, Casey T.; Weatherill, Robin P.; Scott, Jillian Panuzio] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Scott, Jillian Panuzio] Boston Univ, Sch Med, VA Boston Healthcare Syst, Psychol Serv, Boston, MA 02118 USA. [Thomas, Sarah A.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Kang, Han K.] US Dept Vet Affairs, Environm Epidemiol Serv, Washington, DC USA. [Eckhardt, Christopher I.] Purdue Univ, Dept Psychol Sci, W Lafayette, IN 47907 USA. RP Taft, CT (reprint author), VA Boston Healthcare Syst, 116B-4,150 South Huntington Ave, Boston, MA 02130 USA. EM casey.taft@va.gov NR 37 TC 2 Z9 2 U1 2 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD AUG PY 2015 VL 28 IS 4 BP 314 EP 321 DI 10.1002/jts.22017 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CP5HR UT WOS:000359912400007 PM 26201304 ER PT J AU Powell, MA Corbo, V Fonda, JR Otis, JD Milberg, WP McGlinchey, RE AF Powell, Margaret A. Corbo, Vincent Fonda, Jennifer R. Otis, John D. Milberg, William P. McGlinchey, Regina E. TI Sleep Quality and Reexperiencing Symptoms of PTSD Are Associated With Current Pain in US OEF/OIF/OND Veterans With and Without mTBIs SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMATIC BRAIN-INJURY; OPERATIONS ENDURING FREEDOM; POLYTRAUMA CLINICAL TRIAD; TEST-RETEST RELIABILITY; IRAQI FREEDOM; GENDER-DIFFERENCES; BOSTON ASSESSMENT; INTERVIEW; SAMPLE AB Pain, a debilitating condition, is frequently reported by U.S. veterans returning from Afghanistan and Iraq. This study investigated how commonly reported clinical factors were associated with pain and whether these associations differed for individuals with a history of chronic pain. From the Boston metropolitan area, 171 veterans enrolled in the Veterans Affairs Center of Excellence were assessed for current posttraumatic stress disorder (PTSD) symptom severity, current mood and anxiety diagnoses, lifetime traumatic brain injury, combat experiences, sleep quality, and alcohol use. Hierarchical regression models were used to determine the association of these conditions with current pain. Average pain for the previous 30 days, assessed with the McGill Pain Questionnaire, was 30.07 out of 100 (SD = 25.43). Sleep quality, PTSD symptom severity, and alcohol use were significantly associated with pain (R-2 = .24), as were reexperiencing symptoms of PTSD (R-2 = .25). For participants with a history of chronic pain (n = 65), only PTSD symptoms were associated with pain (R-2 = .19). Current pain severity was associated with increased PTSD severity (notably, reexperiencing symptoms), poor sleep quality, and increased alcohol use. These data support the hypothesis that PTSD symptoms influence pain, but suggest that problems with sleep and alcohol use may exacerbate the relationship. Resumen SUENO, TEPT Y DOLOR EN VETERANOS El dolor, una condicion debilitante, es frecuentemente reportado por veteranos norteamericanos que vuelven de Afganistan e Iraq. Este estudio investigo como los factores clinicos comunmente reportados se asociaron con dolor y si estas asociaciones difieren en los individuos con historia de dolor cronico. Desde el area metropolitana de Boston, 171 veteranos enrolados en el Centro de Excelencia de Asuntos Veteranos fueron evaluados en la severidad de los sintomas de TEPT, diagnosticos de estado de animo y ansiedad actuales, LCT (lesion cerebral traumatica) a lo largo de la vida, experiencias de combate, calidad del sueno y consumo de alcohol. Modelos de regresion jerarquica fueron usados para determinar la asociacion de estas condiciones con el dolor actual. El dolor promedio para los 30 dias previos, evaluados con el cuestionario de dolor McGill, fue 30.07 de 100 (DE = 25.43). La calidad del sueno, severidad de los sintomas de TEPT, y uso de alcohol se asociaron significativamente con dolor (R2 = .24), asi como tambien los sintomas de re-experimentacion de TEPT (R2 = .25). Para los participantes con historia de dolor cronico (n = 67), solo los sintomas de TEPT se asociaron con dolor (R2 = .19). La severidad del dolor actual se asocio con mayor severidad de TEPT (mayormente, sintomas de re-experimentacion), mala calidad de sueno, y aumento del consumo de alcohol. Estos datos apoyan la idea que los sintomas de TEPT influyen sobre el dolor, pero sugieren que los problemas del sueno y consumo de alcohol pueden exacerbar esta asociacion. Traditional and Simplified Chinese Abstracts by AsianSTSS ?? : ????????????OEF/OIF/OND????,?????PTSD????????????? ??: ??????,????????????????????????????????????????????,??????????????????????????,171??????????????????????????(PTSD)??????????????????????????(TBIs)???????????????????????????????????????????????????????,??????,??30???????30.07 (SD = 25.43)??????PTSD??????????????????(R2 = .24),PTSD???????????????(R2 = .25)???????????(n = 67)?,??PTSD???????(R2 = .19)?????????PTSD?????(????????)????????????????????????PTSD?????????,?????????????????????? ?? : ????????????OEF/OIF/OND????,?????PTSD????????????? ??: ??????,????????????????????????????????????????????,??????????????????????????,171??????????????????????????(PTSD)??????????????????????????(TBIs)??????????????????????????????????????????????????????,??????,??30???????30.07 (SD = 25.43)??????PTSD??????????????????(R2 = .24),PTSD???????????????(R2 = .25)???????????(n = 67)?,??PTSD???????(R2 = .19)?????????PTSD?????(????????)????????????????????????PTSD?????????,?????????????????????? C1 [Powell, Margaret A.; Corbo, Vincent; Fonda, Jennifer R.; Otis, John D.; Milberg, William P.; McGlinchey, Regina E.] VA Boston Healthcare Syst, Translat Res Ctr TBI & Stress Disorders TRACTS, Boston, MA 02130 USA. [Powell, Margaret A.; Corbo, Vincent; Fonda, Jennifer R.; Otis, John D.; Milberg, William P.; McGlinchey, Regina E.] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr GRECC, Boston, MA 02130 USA. [Corbo, Vincent] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Fonda, Jennifer R.] Boston Univ, Dept Epidemiol, Boston, MA 02215 USA. [Otis, John D.] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. [Otis, John D.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Milberg, William P.; McGlinchey, Regina E.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP McGlinchey, RE (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave, Boston, MA 02130 USA. EM Regina_McGlinchey@hms.harvard.edu RI McGlinchey, Regina/R-1971-2016 FU Translational Research Center for TBI and Stress Disorders (TRACTS); VA Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence [B9254-C]; VA CSR&D Merit Review Award from the United States Department of Veterans Affairs [CX000181] FX This research was supported by the Translational Research Center for TBI and Stress Disorders (TRACTS), a VA Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (B9254-C), and in part by a VA CSR&D Merit Review Award (CX000181) to Regina McGlinchey from the United States Department of Veterans Affairs. The authors would like to thank Wally Musto, CMSgt (Ret) for his recruitment efforts, and Drs. Alexandra Kenna, Catherine Fortier, Brad Brummett, Melissa Amick, and Sara Lippa for the clinical interviews. NR 42 TC 1 Z9 1 U1 1 U2 9 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 2015 VL 28 IS 4 BP 322 EP 329 DI 10.1002/jts.22027 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CP5HR UT WOS:000359912400008 PM 26194844 ER PT J AU Gradus, JL Wisco, BE Luciano, MT Iverson, KM Marx, BP Street, AE AF Gradus, Jaimie L. Wisco, Blair E. Luciano, Matthew T. Iverson, Katherine M. Marx, Brian P. Street, Amy E. TI Traumatic Brain Injury and Suicidal Ideation Among US Operation Enduring Freedom and Operation Iraqi Freedom Veterans SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; SERVICES AB Traumatic brain injury (TBI) is associated with suicidal behavior among veterans, and gender differences in the strength of associations may exist. Almost all research has been limited to Veterans Health Administration (VHA) patients, and it is unclear if findings generalize to veterans who do not use VHA services. We examined gender- and VHA-user-specific associations between TBI related to deployment and postdeployment suicidal ideation in a U.S. national sample of 1,041 female and 880 male Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) veterans. Path analysis was used to estimate TBI and suicidal ideation association, and examine PTSD and depression symptomatology in these associations. TBI was associated with suicidal ideation among male VHA users, OR = 3.64, 95% CI [2.21, 6.01]; and male and female nonusers, OR = 2.24, 95% CI [1.14, 4.44] and OR = 2.65, 95% CI [1.26, 5.58], respectively, in unadjusted analyses. This association was explained by depression symptoms among male and female nonusers. Among male VHA users an association between TBI and suicidal ideation remained when accounting for depression symptoms, OR = 2.50, 95% CI [1.33, 4.71]. Our findings offered evidence of an association between TBI and suicidal ideation among male OEF/OIF VHA users. Resumen LCT e Ideacion Suicida en Veteranos OEF/OIF La Lesion cerebral traumatica (TBI) se asocia con la conducta suicida entre los veteranos, y puede haber diferencias de genero en la fuerza de las asociaciones. Casi toda la investigacion esta limitada a pacientes de la Administracion de Salud de Veteranos (VHA), y no esta claro si los hallazgos se generalizan a los veteranos que no son usuarios de VHA. Evaluamos asociaciones especificas de genero - y usuarios de VHA- en TBI relacionado a ideacion suicida en el despliegue militar y post despliegue militar en una muestra nacional de 1041 mujeres y 880 varones veteranos de OEF y OIF. Se utilizo analisis de pautas para estimar asociacion de TBI e ideacion suicida, y evaluar sintomatologia de TEPT y depresion en estas asociaciones. TBI se asocio con ideacion suicida en varones usuarios VHA (OR: 3.64, 95% CI:[2.21, 6.01]) y en varones y mujeres no usuarios (OR: 2.24, 95% CI:[1.14, 4.44] y OR:2.65, 95% CI:[1.26, 5.58], respectivamente) en analisis no ajustados. Esta asociacion fue explicada por sintomas depresivos entre varones y mujeres no usuarias. Entre los usuarios masculinos VHA una asociacion se mantiene entre TBI e ideacion suicida cuando se incluyen los sintomas depresivos (OR: 2.50, 95% CI:[1.33, 4.71]). Nuestros hallazgos ofrecen evidencia de una asociacion entre TBI e ideacion suicida entre varones OEF/OIF usuarios de VHA. Traditional and Simplified Chinese Abstracts by AsianSTSS ?? : ????????(OEF)??????????(OIF)???????????????? ??: ??????(TBI)????????????,????????????????????????????????????(VHA)???,?????????????????VHA??????????????????????????(OEF)??????????(OIF)???????(1,041????880???),???????TBI???????????,?????VHA??????????????????TBI????????,????????PTSD?????????????????,TBI??????VHA?????? (OR = 3.64, 95% CI = [2.21, 6.01]) ,???VHA???????????? (??? OR = 2.24, 95% CI = [1.14, 4.44] ? OR = 2.65, 95% CI = [1.26, 5.58]) ,?????????VHA???????????????VHA???,????????,TBI????????? (OR = 2.50, 95% CI = [1.33, 4.71])??????OEF/OIF?VHA???TBI????????????? ?? : ????????(OEF)??????????(OIF)???????????????? ??: ??????(TBI)????????????,????????????????????????????????????(VHA)???,?????????????????VHA??????????????????????????(OEF)??????????(OIF)???????(1,041????880???),???????TBI???????????,?????VHA??????????????????TBI????????,????????PTSD????????????????,TBI??????VHA?????? (OR = 3.64, 95% CI = [2.21, 6.01]) ,???VHA???????????? (??? OR = 2.24, 95% CI = [1.14, 4.44] ? OR = 2.65, 95% CI = [1.26, 5.58]) ,?????????VHA???????????????VHA???,????????,TBI????????? (OR = 2.50, 95% CI = [1.33, 4.71])??????OEF/OIF?VHA???TBI????????????? C1 [Gradus, Jaimie L.; Luciano, Matthew T.; Iverson, Katherine M.; Marx, Brian P.; Street, Amy E.] VA Boston HCS, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA. [Gradus, Jaimie L.; Iverson, Katherine M.; Marx, Brian P.; Street, Amy E.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Gradus, Jaimie L.] Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02118 USA. [Wisco, Blair E.] Univ N Carolina, Dept Psychol, Greensboro, NC 27412 USA. RP Gradus, JL (reprint author), VA Boston HCS, 150 South Huntington Ave, Boston, MA 02130 USA. EM Jaimie.gradus@va.gov OI Gradus, Jaimie/0000-0003-1459-5327 FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSR&D) Services as part of her HSR&D Career Development Award [CDA 10-029] FX Dr. Iverson's contribution to this work was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSR&D) Services as part of her HSR&D Career Development Award (CDA 10-029). The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 18 TC 1 Z9 1 U1 1 U2 16 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 2015 VL 28 IS 4 BP 361 EP 365 DI 10.1002/jts.22021 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CP5HR UT WOS:000359912400013 PM 26179483 ER PT J AU Dilwali, S Briet, MC Kao, SY Fujita, T Landegger, LD Platt, MP Stankovic, KM AF Dilwali, Sonam Briet, Martijn C. Kao, Shyan-Yuan Fujita, Takeshi Landegger, Lukas D. Platt, Michael P. Stankovic, Konstantina M. TI Preclinical validation of anti-nuclear factor-kappa B therapy to inhibit human vestibular schwannoma growth SO MOLECULAR ONCOLOGY LA English DT Article DE Vestibular schwannoma; Network analysis; NF-kappa B; TNF; BAY 11-7082; Curcumin ID NEUROFIBROMATOSIS TYPE-2; EXPRESSION; CURCUMIN; CELLS; PHOSPHORYLATION; ACTIVATION; BEVACIZUMAB; GENES AB Vestibular schwannomas (VSs), the most common tumors of the cerebellopontine angle, arise from Schwann cells lining the vestibular nerve. Pharmacotherapies against VS are almost non-existent. Although the therapeutic inhibition of inflammatory modulators has been established for other neoplasms, it has not been explored in VS. A bioinformatic network analysis of all genes reported to be differentially expressed in human VS revealed a pro-inflammatory transcription factor nuclear factor-kappa B (NF-kappa B) as a central molecule in VS pathobiology. Assessed at the transcriptional and translational level, canonical NF-kappa B complex was aberrantly activated in human VS and derived VS cultures in comparison to control nerves and Schwann cells, respectively. Cultured primary VS cells and VS-derived human cell line HEI-193 were treated with specific NF-kappa B siRNAs, experimental NF-kappa B inhibitor BAY11-7082 (BAY11) and clinically relevant NF-kappa B inhibitor curcumin. Healthy human control Schwann cells from the great auricular nerve were also treated with BAY11 and curcumin to assess toxicity. All three treatments significantly reduced proliferation in primary VS cultures and HEI-193 cells, with siRNA, 5 mu M BAY11 and 50 mu M curcumin reducing average proliferation (standard error of mean) to 62.33% +/- 10.59%, 14.3 +/- 9.7%, and 23.0 +/- 20.9% of control primary VS cells, respectively. These treatments also induced substantial cell death. Curcumin, unlike BAY11, also affected primary Schwann cells. This work highlights NF-kappa B as a key modulator in VS cell proliferation and survival and demonstrates therapeutic efficacy of directly targeting NF-kappa B in VS. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 [Dilwali, Sonam; Briet, Martijn C.; Kao, Shyan-Yuan; Fujita, Takeshi; Landegger, Lukas D.; Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Labs, Boston, MA 02114 USA. [Dilwali, Sonam; Stankovic, Konstantina M.] Haruard MIT Program Speech & Hearing Biosci & Tec, Cambridge, MA 02139 USA. [Fujita, Takeshi; Landegger, Lukas D.; Platt, Michael P.; Stankovic, Konstantina M.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Briet, Martijn C.] Leiden Univ, Med Ctr, Dept Otorhinolaryngol, NL-2333 ZA Leiden, Netherlands. [Platt, Michael P.] Boston Univ, Dept Otolaryngol Head & Neck Surg, Boston, MA 02118 USA. RP Stankovic, KM (reprint author), 243 Charles St, Boston, MA 02114 USA. EM sdilwaliutsw@gmail.com; martijnbriet@gmail.com; Shyan-Yuan_Kao@meei.harvard.edu; takeshi_fujita@meei.harvard.edu; Lukas_landegger@meei.harvard.edu; Michael.Platt@bmc.org; konstantina_stankovic@meei.harvard.edu OI Landegger, Lukas D./0000-0002-9660-2625 FU National Institute of Deafness and Other Communication Disorders [KO8DC010419-D1, T32DC00038]; Department of Defense [W81XWH-14-1-0091]; Bertarelli Foundation FX The funding sources were National Institute of Deafness and Other Communication Disorders (KO8DC010419-D1 to K.M.S.; T32DC00038 to K.M.S., S.D.), Department of Defense (W81XWH-14-1-0091 to K.M.S.) and the Bertarelli Foundation (K.M.S.). The funding sources had no direct involvement in this work. NR 43 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1574-7891 EI 1878-0261 J9 MOL ONCOL JI Mol. Oncol. PD AUG PY 2015 VL 9 IS 7 BP 1359 EP 1370 DI 10.1016/j.molonc.2015.03.009 PG 12 WC Oncology SC Oncology GA CP4XB UT WOS:000359884800011 PM 25891780 ER PT J AU Wang, ZH Wei, M Zhang, HP Chen, HY Germana, S Huang, CA Madsen, JC Sachs, DH Wang, ZR AF Wang, Zhaohui Wei, Min Zhang, Huiping Chen, Hongyuan Germana, Sharon Huang, Christene A. Madsen, Joren C. Sachs, David H. Wang, Zhirui TI Diphtheria-toxin based anti-human CCR4 immunotoxin for targeting human CCR4(+) cells in vivo SO MOLECULAR ONCOLOGY LA English DT Article DE CCR4; Immunotoxin; CCR4(+) tumor; Treg; Diphtheria toxin; Pichia Pastoris expression ID REGULATORY T-CELLS; IL-2 FUSION TOXIN; PICHIA-PASTORIS; TUMOR-IMMUNITY; CD25(+) CELLS; CANCER; IMMUNOTHERAPY; EXPRESSION; VACCINES AB CC chemokine receptor 4 (CCR4) has attracted much attention as a promising therapeutic drug target for CCR4(+) tumor cells and Tregs. CCR4 is expressed on some tumor cells such as T-cell acute lymphoblastic leukemia (ALL), adult T-cell leukemia/lymphoma (ATLL), adult peripheral T cell lymphoma (PTCL) and cutaneous T cell lymphoma (CTCL). CCR4 is also expressed on majority of Tregs, mainly effector Tregs. In this study we have successfully developed three versions of diphtheria-toxin based anti-human CCR4 immunotoxins (monovalent, bivalent and single-chain fold-back diabody). Binding analysis by flow cytometry showed that all three versions of the anti-human CCR4 immunotoxins bound to the human CCR4(+) tumor cell line as well as CCR4(+) human PBMC. The bivalent isoform bound stronger than its monovalent counterpart and the single-chain foldback diabody isoform was the strongest among the three versions. In vitro efficacy analysis demonstrated that the bivalent isoform was 20 fold more potent in inhibiting cellular proliferation and protein synthesis in human CCR4 tumor cells compared to the monovalent anti-human CCR4 immunotoxin. The single-chain fold-back diabody isoforrn was 10 fold more potent than its bivalent counterpart and 200 fold more potent than its monovalent counterpart. The in vivo efficacy was assessed using a human CCR4(+) tumor-bearing mouse model. The immunotoxin significantly prolonged the survival of tumor-bearing NOD/SCID IL-2 receptor gamma(-/-) (NSG) mice injected with human CCR4(+) acute lymphoblastic leukemia cells compared with the control group. This novel anti-human CCR4 immunotoxin is a promising drug candidate for targeting human CCR4(+) tumor cells and Tregs in vivo. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 [Wang, Zhaohui; Wei, Min; Zhang, Huiping; Chen, Hongyuan; Germana, Sharon; Huang, Christene A.; Madsen, Joren C.; Sachs, David H.; Wang, Zhirui] Massachusetts Gen Hosp, Ctr Transplantat Sci, Boston, MA 02129 USA. [Wang, Zhaohui; Wei, Min; Zhang, Huiping; Chen, Hongyuan; Germana, Sharon; Huang, Christene A.; Madsen, Joren C.; Sachs, David H.; Wang, Zhirui] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Sachs, David H.] Massachusetts Gen Hosp, Ctr Transplantat Sci, TBRC Labs, Boston, MA 02129 USA. [Madsen, Joren C.] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02129 USA. RP Wang, ZR (reprint author), Massachusetts Gen Hosp, Ctr Transplantat Sci, MGH East, Bldg 149-6113,13th St, Boston, MA 02129 USA. EM zwang7@mgh.harvard.edu NR 24 TC 3 Z9 3 U1 2 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1574-7891 EI 1878-0261 J9 MOL ONCOL JI Mol. Oncol. PD AUG PY 2015 VL 9 IS 7 BP 1458 EP 1470 DI 10.1016/j.molonc.2015.04.004 PG 13 WC Oncology SC Oncology GA CP4XB UT WOS:000359884800019 PM 25958791 ER PT J AU Scheller, EL Doucette, CR Learman, BS Cawthorn, WP Khandaker, S Schell, B Wu, B Ding, SY Bredella, MA Fazeli, PK Khoury, B Jepsen, KJ Pilch, PF Klibanski, A Rosen, CJ MacDougald, OA AF Scheller, Erica L. Doucette, Casey R. Learman, Brian S. Cawthorn, William P. Khandaker, Shaima Schell, Benjamin Wu, Brent Ding, Shi-Ying Bredella, Miriam A. Fazeli, Pouneh K. Khoury, Basma Jepsen, Karl J. Pilch, Paul F. Klibanski, Anne Rosen, Clifford J. MacDougald, Ormond A. TI Region-specific variation in the properties of skeletal adipocytes reveals regulated and constitutive marrow adipose tissues SO NATURE COMMUNICATIONS LA English DT Article ID BONE-MARROW; FAT COMPOSITION; METABOLISM; CELLS; MICE; RATS; CAVEOLIN-1; ACID; DIFFERENTIATION; IDENTIFICATION AB Marrow adipose tissue (MAT) accumulates in diverse clinical conditions but remains poorly understood. Here we show region-specific variation in MAT adipocyte development, regulation, size, lipid composition, gene expression and genetic determinants. Early MAT formation in mice is conserved, whereas later development is strain dependent. Proximal, but not distal tibial, MAT is lost with 21-day cold exposure. Rat MAT adipocytes from distal sites have an increased proportion of monounsaturated fatty acids and expression of Scd1/Scd2, Cebpa and Cebpb. Humans also have increased distal marrow fat unsaturation. We define proximal 'regulated' MAT (rMAT) as single adipocytes interspersed with active haematopoiesis, whereas distal 'constitutive' MAT (cMAT) has low haematopoiesis, contains larger adipocytes, develops earlier and remains preserved upon systemic challenges. Loss of rMAT occurs in mice with congenital generalized lipodystrophy type 4, whereas both rMAT and cMAT are preserved in mice with congenital generalized lipodystrophy type 3. Consideration of these MAT subpopulations may be important for future studies linking MAT to bone biology, haematopoiesis and whole-body metabolism. C1 [Scheller, Erica L.; Learman, Brian S.; Cawthorn, William P.; Khandaker, Shaima; Schell, Benjamin; Wu, Brent; MacDougald, Ormond A.] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48105 USA. [Scheller, Erica L.; Learman, Brian S.; Cawthorn, William P.; Khandaker, Shaima; Schell, Benjamin; Wu, Brent; MacDougald, Ormond A.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48105 USA. [Doucette, Casey R.; Rosen, Clifford J.] Maine Med Ctr Res Inst, Ctr Clin & Translat Res, Scarborough, ME 04074 USA. [Ding, Shi-Ying; Pilch, Paul F.] Boston Univ, Dept Biochem, Sch Med, Boston, MA 02118 USA. [Bredella, Miriam A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Bredella, Miriam A.; Fazeli, Pouneh K.; Klibanski, Anne] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Fazeli, Pouneh K.; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Khoury, Basma; Jepsen, Karl J.] Univ Michigan, Dept Orthopaed Surg, Ann Arbor, MI 48109 USA. RP Scheller, EL (reprint author), Washington Univ, Div Bone & Mineral Dis, Dept Internal Med, St Louis, MO 63110 USA. EM eschelle@dom.wustl.edu; macdouga@umich.edu OI MacDougald, Ormond/0000-0001-6907-7960; Scheller, Erica/0000-0002-1551-3816 FU National Institutes of Health [R24-DK092759, K99-DE024178, P30-DK089503, S10-RR026336, AR44927, R01-DK097708, K23-DK094820]; Lilly Innovation Fellowship Award; Royal Commission for the Exhibition of 1851 (UK) FX This work was supported by grants from the National Institutes of Health including R24-DK092759 (O.A.M., C.J.R. and A.K.), K99-DE024178 (E.L.S.), P30-DK089503 to the Michigan Nutrition Obesity Research Center, S10-RR026336 (K.J.J.), AR44927 (K.J.J. and B.K.), R01-DK097708 (P.F.P) and K23-DK094820 (P.K.F.). W.P.C. was supported by a Lilly Innovation Fellowship Award and previously by a Postdoctoral Research Fellowship from the Royal Commission for the Exhibition of 1851 (UK). We thank the metabolomics core at Michigan and Arun Das for performing the lipidomic analyses; Michelle Lynch and the microCT core at the University of Michigan; Hoai An Pham for her technical help; and Hiroyuki Mori and Sebastian Parlee for their insight and advice. NR 48 TC 25 Z9 26 U1 2 U2 15 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 2015 VL 6 AR 7808 DI 10.1038/ncomms8808 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CQ1FA UT WOS:000360341500001 PM 26245716 ER PT J AU Yu, F Duong, T Tantiwongkosi, B AF Yu, Fang Duong, Timothy Tantiwongkosi, Bundhit TI Advanced MR Imaging of the Visual Pathway SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article DE Visual pathway; Retina; Lateral geniculate nucleus; MR imaging; Diffusion tensor imaging; Diffusion-weighted imaging; Magnetization transfer ratio; Functional imaging; Retinotopic mapping ID LATERAL GENICULATE-NUCLEUS; ISCHEMIC OPTIC NEUROPATHY; MAGNETIZATION-TRANSFER; HIGH-RESOLUTION; BLOOD-FLOW; RETINOTOPIC ORGANIZATION; INITIAL-EXPERIENCE; SINGLE-SHOT; GLAUCOMA; RETINA AB Vision is one of our most vital senses, deriving from the eyes as well as structures deep within the intracranial compartment. MR imaging, through its wide selection of sequences, offers an array of structural and functional imaging tools to interrogate this intricate system. This review describes several advanced MR imaging sequences and explores their potential clinical applications as well as areas for further development. C1 [Yu, Fang; Tantiwongkosi, Bundhit] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Duong, Timothy] Res Imaging Inst, San Antonio, TX 78229 USA. [Tantiwongkosi, Bundhit] South Texas Vet Hlth Care Syst, Imaging Serv, San Antonio, TX 78229 USA. RP Yu, F (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, 7703 Floyd Curl Dr,Mail Stop 7800, San Antonio, TX 78229 USA. EM yuf@uthscsa.edu NR 42 TC 0 Z9 0 U1 1 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 1052-5149 EI 1557-9867 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD AUG PY 2015 VL 25 IS 3 BP 383 EP + DI 10.1016/j.nic.2015.05.003 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CP4SY UT WOS:000359874100005 PM 26208415 ER PT J AU Vachha, BA Robson, CD AF Vachha, Behroze A. Robson, Caroline D. TI Imaging of Pediatric Orbital Diseases SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article DE Pediatric; Orbit; Ocular; CT; MR imaging; Congenital; Tumor; Vascular ID CAROTID-CAVERNOUS FISTULA; HIPPEL-LINDAU-DISEASE; INTRACRANIAL VASCULAR ANOMALIES; TUMOR-LIKE LESIONS; AICARDI-SYNDROME; PATHOLOGICAL CORRELATION; EYE; MALFORMATIONS; DISORDERS; RHABDOMYOSARCOMA AB This article reviews a variety of congenital and developmental disorders of the pediatric orbit with particular emphasis on ocular lesions, followed by a description of developmental and neoplastic orbital and ocular masses. The relationship of these diseases to various syndromes and/or known genetic mutations is also highlighted. C1 [Vachha, Behroze A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Robson, Caroline D.] Harvard Univ, Sch Med, Dept Radiol, Boston Childrens Hosp, Boston, MA 02115 USA. RP Robson, CD (reprint author), Harvard Univ, Sch Med, Dept Radiol, Boston Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM caroline.robson@childrens.harvard.edu NR 66 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1052-5149 EI 1557-9867 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD AUG PY 2015 VL 25 IS 3 BP 477 EP + DI 10.1016/j.nic.2015.05.009 PG 26 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CP4SY UT WOS:000359874100011 PM 26208421 ER PT J AU Daroui, P Jabbour, SK Herman, JM Abdel-Wahab, M Azad, N Blackstock, AW Das, P Goodman, KA Hong, TS Jones, WE Kaur, H Konski, AA Koong, AC Kumar, R Pawlik, TM Small, W Thomas, CR Suh, WW AF Daroui, Parima Jabbour, Salma K. Herman, Joseph M. Abdel-Wahab, May Azad, Nilofer Blackstock, A. William Das, Prajnan Goodman, Karyn A. Hong, Theodore S. Jones, William E., III Kaur, Harmeet Konski, Andre A. Koong, Albert C. Kumar, Rachit Pawlik, Timothy M. Small, William, Jr. Thomas, Charles R., Jr. Suh, W. Warren TI ACR Appropriateness Criteria (R) Resectable Stomach Cancer SO ONCOLOGY-NEW YORK LA English DT Review ID PHASE-III TRIAL; LOCALIZED GASTRIC ADENOCARCINOMA; LYMPH-NODE DISSECTION; DATA-BASE REPORT; RADIATION-THERAPY; PERIOPERATIVE CHEMOTHERAPY; COMBINED 5-FLUOROURACIL; ADJUVANT CHEMOTHERAPY; PATHOLOGICAL RESPONSE; SURGERY AB For resectable gastric cancer, perioperative chemotherapy or adjuvant chemoradiation with chemotherapy are standards of care. The decision making for adjuvant therapeutic management can depend on the stage of the cancer, lymph node positivity, and extent of surgical resection. After gastric cancer resection, postoperative chemotherapy combined with chemoradiation should be incorporated in cases of DO lymph node dissection, positive regional lymph nodes, poor clinical response to induction chemotherapy, or positive margins. In the setting of a D2 lymph node dissection, especially those with negative regional lymph nodes, adjuvant chemotherapy alone could be considered. The American College of Radiology (ACR) Appropriateness Criteria (R) are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review includes an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. C1 [Daroui, Parima] Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Orange, CA 92668 USA. [Jabbour, Salma K.] Rutgers State Univ, Rutgers Canc Inst New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ 08903 USA. [Herman, Joseph M.; Azad, Nilofer] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Abdel-Wahab, May] Cleveland Clin, Cleveland, OH 44106 USA. [Blackstock, A. William] Wake Forest Univ, Winston Salem, NC 27109 USA. [Das, Prajnan; Kaur, Harmeet] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Goodman, Karyn A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Hong, Theodore S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jones, William E., III] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Konski, Andre A.] Chester Cty Hosp, W Chester, PA USA. [Koong, Albert C.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Kumar, Rachit] Banner MD Anderson Canc Ctr, Gilbert, AZ USA. [Pawlik, Timothy M.] Johns Hopkins Univ, Baltimore, MD USA. [Small, William, Jr.] Loyola Univ Chicago, Stritch Sch Med, Maywood, IL USA. [Thomas, Charles R., Jr.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Suh, W. Warren] Canc Ctr Santa Barbara, Santa Barbara, CA USA. RP Jabbour, SK (reprint author), Amer Coll Radiol, 1891 Preston White Dr, Reston, VA 20191 USA. EM jabbousk@cinj.rutgers.edu FU Genentech; Nucletron FX Dr. Das receives research support from Genentech. Dr. Herman receives research support from Nucletron and Genentech. The other authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article. NR 45 TC 1 Z9 1 U1 0 U2 0 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 2015 VL 29 IS 8 BP 595 EP 603 PG 9 WC Oncology SC Oncology GA CP5AM UT WOS:000359893700011 PM 26281845 ER PT J AU Goldstein, JN Ibrahim, SA Frankel, ES Mao, JJ AF Goldstein, Jennifer N. Ibrahim, Said A. Frankel, Eitan S. Mao, Jun J. TI Race, Pain, and Beliefs Associated with Interest in Complementary and Alternative Medicine among Inner City Veterans SO PAIN MEDICINE LA English DT Article DE Complementary Medicine; Complementary Therapies; Pain Management; Pain Medicine; Perception ID CHRONIC NONCANCER PAIN; LOW-BACK-PAIN; PRESCRIPTION OPIOID INITIATION; CHRONIC NONMALIGNANT PAIN; MILITARY VETERANS; UNITED-STATES; CARE-SYSTEM; HEALTH; ACUPUNCTURE; PERCEPTIONS AB ObjectiveTo investigate the prevalence and determinants of complementary and alternative medicine (CAM) interest level among a racially diverse cohort of inner city veterans who receive primary care at the VA Medical Center. DesignCross-sectional survey study SettingPhiladelphia VA Medical Center SubjectsPrimary care patients (n=258) MethodsInterest in CAM was measured using a single item question. Patient treatment beliefs were assessed using validated instruments. We evaluated factors associated with patient interest in CAM using a multivariate logistic regression model. ResultsIn this sample of 258 inner city primary care VA patients, interest in CAM was high 80% (n=206). Interest in CAM was strongly associated with African American race [adjusted odds ratio (AOR) 2.19, 95% Confidence Interval (CI) 1.05-4.60, P=0.037], higher levels of education (AOR 4.33, 95% CI 1.80-10.40, P=0.001), presence of moderate to severe pain (AOR 2.02, 95% CI 1.02-4.78, P=0.043), and expectations of benefit from CAM use (AOR 1.21, 95% CI 1.06-1.36, P=0.004). ConclusionsCAM approaches have broad appeal within this inner city cohort of veterans, particularly among African Americans, those that experience pain and those that expect greater benefit from CAM. These findings may inform the development of patient-centered integrative pain management for veterans. C1 [Goldstein, Jennifer N.] Christiana Care Hlth Syst, Dept Med, Newark, DE 19713 USA. [Ibrahim, Said A.] Philadelphia VA Med Ctr, Ctr Hlth Equ & Promot, Philadelphia, PA USA. [Frankel, Eitan S.] Univ Illinois, Coll Med, Chicago, IL USA. [Mao, Jun J.] Univ Penn, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. RP Goldstein, JN (reprint author), Christiana Care Hlth Syst, Dept Med, Ammon 2E72A,4755 Ogletown Stanton Rd, Newark, DE 19713 USA. EM jgoldstein@christianacare.org NR 37 TC 2 Z9 2 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD AUG PY 2015 VL 16 IS 8 BP 1467 EP 1474 DI 10.1111/pme.12756 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA CP7FR UT WOS:000360053100004 PM 26287564 ER PT J AU Pang, CE Sarraf, D Freund, KB AF Pang, Claudine E. Sarraf, David Freund, K. Bailey TI Untitled Reply SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Letter ID HIGHLY MYOPIC EYES; CHOROIDAL THICKNESS; VISUAL-ACUITY C1 [Pang, Claudine E.; Freund, K. Bailey] Macula Consultants New York, Retina, Vitreous, New York, NY 10022 USA. [Pang, Claudine E.; Freund, K. Bailey] Manhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retinal Res Ctr, New York, NY 10021 USA. [Sarraf, David] Univ Calif Los Angeles, Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, Los Angeles, CA USA. [Sarraf, David] Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. [Freund, K. Bailey] NYU, Sch Med, Dept Ophthalmol, New York, NY USA. RP Pang, CE (reprint author), Macula Consultants New York, Retina, Vitreous, New York, NY 10022 USA. FU NEI NIH HHS [R24 EY019861, R01 EY021163] NR 6 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 0275-004X EI 1539-2864 J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD AUG PY 2015 VL 35 IS 8 BP e47 EP e48 DI 10.1097/IAE.0000000000000676 PG 2 WC Ophthalmology SC Ophthalmology GA CP4HZ UT WOS:000359843900002 PM 26131589 ER PT J AU Hundert, SA White, AA Reilly, DF AF Hundert, Samuel A. White, Andrew A. Reilly, Dominic F. TI Number of General Medicine Hospital Admissions Performed by Internal Medicine Residents Before and After the 2011 Duty-Hour Regulations SO SOUTHERN MEDICAL JOURNAL LA English DT Article DE admissions; education; internal medicine; 2011 resident duty-hour regulations ID PATIENT-CARE; EDUCATION; SUPERVISION; PERCEPTIONS; DURATION; QUALITY; RISK AB Objectives In July 2011 the Accreditation Council for Graduate Medical Education implemented new resident duty-hour regulations in an effort to improve resident well-being, clinical performance, and patient care. These regulations have the potential, however, to reduce the number of new patient encounters handled by trainees and thereby could be detrimental to resident education. Our objective was to describe how the 2011 duty-hour regulations affected the volume of new inpatient general medicine encounters at two large academic medical centers. We looked specifically at new patient encounters because we assumed they provided the richest learning opportunities. We hypothesized that the implementation of the Accreditation Council for Graduate Medical Education regulations would be associated with a reduction in the number of new admissions per day and result in a decrease in the number of annual admissions performed by first-year medical residents. Methods We conducted a retrospective ecological study. We reviewed general medicine admissions data from two large academic hospitals affiliated with the University of Washington: Harborview Medical Center and the University of Washington Medical Center. We abstracted the number of admissions, source of admission, and average intern census on 56 randomly selected days before and after the regulations were implemented (academic years 2010-2011 [AY11] and 2011-2012 [AY12]). We generated descriptive statistics (means, proportions, and 95% confidence intervals) and then used a two-sample t test to compare the number of admissions per day, admission source, and average daily intern census between AY11 and AY12. Results At the University of Washington Medical Center, single-intern teams admitted 4.5 patients per day in AY11 compared with 3.1 in AY12 (P < 0.001). At Harborview Medical Center, two-intern teams admitted 11.1 patients per day in AY11 versus 7.9 in AY12 (P < 0.001). Night interns admitted 0.9 patients per shift in AY11 versus 2.4 in AY12 (P < 0.001). After implementing the new duty hours, daytime admissions from the emergency department decreased and admissions as transfers from the intensive care unit increased. The average intern census was not affected by the duty-hour regulations. Conclusions Medicine residents admit fewer patients on daytime inpatient general medicine services under the new duty-hour regulations; however, this is completely offset by an increase in the number of admissions performed on the night rotation, resulting in no net change in the total number of new inpatient encounters handled by first-year medical residents during the course of the academic year. Although this is reassuring, changes that were made in response to the work-hour rules have altered how new admissions are distributed to teams, which has important implications for curricular design and supervision. C1 [Hundert, Samuel A.; White, Andrew A.; Reilly, Dominic F.] Univ Washington, Dept Internal Med, Seattle, WA 98195 USA. RP Hundert, SA (reprint author), VA Puget Sound Healthcare Syst, Hosp & Specialty Med, 1660 S Columbian Way, Seattle, WA 98108 USA. EM hunderts@uw.edu NR 23 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0038-4348 EI 1541-8243 J9 SOUTH MED J JI South.Med.J. PD AUG PY 2015 VL 108 IS 8 BP 476 EP 481 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA CP3WC UT WOS:000359812400006 PM 26280773 ER PT J AU Auriel, E Westover, MB Bianchi, MT Reijmer, Y Martinez-Ramirez, S Ni, J Van Etten, E Frosch, MP Fotiadis, P Schwab, K Vashkevich, A Boulouis, G Younger, AP Johnson, KA Sperling, RA Hedden, T Gurol, ME Viswanathan, A Greenberg, SM AF Auriel, Eitan Westover, M. Brandon Bianchi, Matt T. Reijmer, Yael Martinez-Ramirez, Sergi Ni, Jun Van Etten, Ellis Frosch, Matthew P. Fotiadis, Panagiotis Schwab, Kris Vashkevich, Anastasia Boulouis, Gregoire Younger, Alayna P. Johnson, Keith A. Sperling, Reisa A. Hedden, Trey Gurol, M. Edip Viswanathan, Anand Greenberg, Steven M. TI Estimating Total Cerebral Microinfarct Burden From Diffusion-Weighted Imaging SO STROKE LA English DT Article DE brain; cerebral hemorrhage; cerebral infarction; diffusion magnetic resonance imaging; mild cognitive impairment ID INTRACEREBRAL HEMORRHAGE; CORTICAL MICROINFARCTS; AMYLOID ANGIOPATHY; ACUTE INFARCTS; ACUTE STROKE; DEMENTIA; LESIONS; MRI; DISEASE; SILENT AB Background and Purpose-Cerebral microinfarcts (CMI) are important contributors to vascular cognitive impairment. Magnetic resonance imaging diffusion-weighted imaging (DWI) hyperintensities have been suggested to represent acute CMI. We aim to describe a mathematical method for estimating total number of CMI based on the presence of incidental DWI lesions. Methods-We reviewed magnetic resonance imaging scans of subjects with cognitive decline, cognitively normal subjects and previously reported subjects with past intracerebral hemorrhage (ICH). Based on temporal and spatial characteristics of DWI lesions, we estimated the annual rate of CMI needed to explain the observed rate of DWI lesion detection in each group. To confirm our estimates, we performed extensive sampling for CMI in the brain of a deceased subject with past lobar ICH who found to have a DWI lesion during life. Results-Clinically silent DWI lesions were present in 13 of 343 (3.8%) cognitively impaired and 10 of 199 (5%) cognitively intact normal non-ICH patients, both lower than the incidence in the past ICH patients (23 of 178; 12.9%; P<0.0006). The predicted annual incidence of CMI ranges from 16 to 1566 for non-ICH and 50 to 5041 for ICH individuals. Histological sampling revealed a total of 60 lesions in 32 sections. Based on previously reported methods, this density of CMI yields an estimated total brain burden maximum likelihood estimate of 9321 CMIs (95% confidence interval, 7255-11 990). Conclusions-Detecting even a single DWI lesion suggests an annual incidence of hundreds of new CMI. The cumulative effects of these lesions may directly contribute to small-vessel-related vascular cognitive impairment. C1 [Auriel, Eitan; Westover, M. Brandon; Bianchi, Matt T.; Reijmer, Yael; Martinez-Ramirez, Sergi; Ni, Jun; Van Etten, Ellis; Fotiadis, Panagiotis; Schwab, Kris; Vashkevich, Anastasia; Boulouis, Gregoire; Gurol, M. Edip; Viswanathan, Anand; Greenberg, Steven M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,J Philip Kistler Stroke Res Ctr, Boston, MA USA. [Frosch, Matthew P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Neuropathol Serv,CS Kubik Lab Neuropa, Boston, MA USA. [Younger, Alayna P.; Johnson, Keith A.; Sperling, Reisa A.; Hedden, Trey] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol,Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Ctr Stroke Res, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM sgreenberg@partners.org RI Gurol, Edip/J-2279-2014; OI Gurol, Edip/0000-0002-2169-4457; Boulouis, Gregoire/0000-0001-8422-9205 FU National Institutes of Health [R01AG026484] FX This project was supported in part by R01AG026484 from the National Institutes of Health. The funding entities had no involvement in study design, data collection, analysis, and interpretation, writing of the article, or the decision to submit for publication. NR 33 TC 5 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD AUG PY 2015 VL 46 IS 8 BP 2129 EP 2135 DI 10.1161/STROKEAHA.115.009208 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CP6CP UT WOS:000359972200032 PM 26159796 ER PT J AU Radmanesh, F Falcone, GJ Anderson, CD McWilliams, D Devan, WJ Brown, WM Battey, TWK Ayres, AM Raffeld, MR Schwab, K Sun, G Deka, R Viswanathan, A Goldstein, JN Greenberg, SM Tirschwell, DL Silliman, SL Selim, M Meschia, JF Brown, DL Worrall, BB Langefeld, CD Woo, D Rosand, J AF Radmanesh, Farid Falcone, Guido J. Anderson, Christopher D. McWilliams, David Devan, William J. Brown, W. Mark Battey, Thomas W. K. Ayres, Alison M. Raffeld, Miriam R. Schwab, Kristin Sun, Guangyun Deka, Ranjan Viswanathan, Anand Goldstein, Joshua N. Greenberg, Steven M. Tirschwell, David L. Silliman, Scott L. Selim, Magdy Meschia, James F. Brown, Devin L. Worrall, Bradford B. Langefeld, Carl D. Woo, Daniel Rosand, Jonathan TI Rare Coding Variation and Risk of Intracerebral Hemorrhage SO STROKE LA English DT Article DE apolipoproteins E; cerebral hemorrhage; genome-wide association study ID ASSOCIATION AB Background and Purpose-Intracerebral hemorrhage has a substantial genetic component. We performed a preliminary search for rare coding variants associated with intracerebral hemorrhage. Methods-A total of 757 cases and 795 controls were genotyped using the Illumina HumanExome Beadchip (Illumina, Inc, San Diego, CA). Meta-analyses of single-variant and gene-based association were computed. Results-No rare coding variants were associated with intracerebral hemorrhage. Three common variants on chromosome 19 q13 at an established susceptibility locus, encompassing TOMM40, APOE, and APOC1, met genome-wide significance (P < 5e-08). After adjusting for the APOE epsilon alleles, this locus was no longer convincingly associated with intracerebral hemorrhage. No gene reached genome-wide significance level in gene-based association testing. Conclusions-Although no coding variants of large effect were detected, this study further underscores a major challenge for the study of genetic susceptibility loci; large sample sizes are required for sufficient power except for loci with large effects. C1 [Radmanesh, Farid; Falcone, Guido J.; Anderson, Christopher D.; Devan, William J.; Battey, Thomas W. K.; Raffeld, Miriam R.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Radmanesh, Farid; Falcone, Guido J.; Anderson, Christopher D.; Devan, William J.; Battey, Thomas W. K.; Raffeld, Miriam R.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. [Radmanesh, Farid; Falcone, Guido J.; Anderson, Christopher D.; Devan, William J.; Battey, Thomas W. K.; Ayres, Alison M.; Raffeld, Miriam R.; Schwab, Kristin; Viswanathan, Anand; Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Radmanesh, Farid; Falcone, Guido J.; Anderson, Christopher D.; Devan, William J.; Battey, Thomas W. K.; Raffeld, Miriam R.; Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [McWilliams, David; Brown, W. Mark; Langefeld, Carl D.] Wake Forest Sch Med, Ctr Publ Hlth Genom, Dept Biostat Sci, Winston Salem, NC USA. [Devan, William J.] Quinnipiac Univ, Frank H Netter MD Sch Med, Hamden, CT USA. [Sun, Guangyun; Deka, Ranjan] Univ Cincinnati, Coll Med, Dept Environm Hlth, Cincinnati, OH 45221 USA. [Woo, Daniel] Univ Cincinnati, Coll Med, Dept Neurol & Rehabil, Cincinnati, OH 45221 USA. [Tirschwell, David L.] Univ Washington, Harborview Med Ctr, Dept Neurol, Seattle, WA 98104 USA. [Silliman, Scott L.] Univ Florida, Coll Med, Dept Neurol, Jacksonville, FL USA. [Selim, Magdy] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Brown, Devin L.] Univ Michigan Hlth Syst, Dept Neurol, Ann Arbor, MI USA. [Worrall, Bradford B.] Univ Virginia Hlth Syst, Dept Neurol, Charlottesville, VA USA. [Worrall, Bradford B.] Univ Virginia Hlth Syst, Dept Publ Hlth Sci, Charlottesville, VA USA. RP Rosand, J (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 6810, Boston, MA 02114 USA. EM jrosand@partners.org RI Goldstein, Joshua/H-8953-2016; Falcone, Guido/L-2287-2016; OI Falcone, Guido/0000-0002-6407-0302; Anderson, Christopher/0000-0002-0053-2002 FU National Institutes of Health-National Institute of Neurological Disorders and Stroke (NIH-NINDS) [R01NS073344, R01NS059727, 5K23NS059774]; American Heart Association [0755984T]; American Brain Foundation; Massachusetts General Hospital Institute for Heart, Vascular and Stroke Care; NIH FX This study was supported by grants R01NS073344, R01NS059727, and 5K23NS059774 from the National Institutes of Health-National Institute of Neurological Disorders and Stroke (NIH-NINDS) and 0755984T from the American Heart Association. Computation support was provided, in part, by the Wake Forest School of Medicine Center for Public Health Genomics. Dr Anderson received research grants from the NIH-NINDS, American Brain Foundation, and Massachusetts General Hospital Institute for Heart, Vascular and Stroke Care. Dr Worrall received a research grant from the NIH. Dr Rosand received research grants from the NIH. NR 8 TC 2 Z9 2 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD AUG PY 2015 VL 46 IS 8 BP 2299 EP 2301 DI 10.1161/STROKEAHA.115.009838 PG 3 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CP6CP UT WOS:000359972200056 PM 26111891 ER PT J AU Linfante, I Walker, GR Castonguay, AC Dabus, G Starosciak, AK Yoo, AJ Abou-Chebl, A Britz, GW Marden, FA Alvarez, A Gupta, R Sun, CHJ Martin, C Holloway, WE Mueller-Kronast, N English, JD Malisch, TW Bozorgchami, H Xavier, A Rai, AT Froehler, MT Badruddin, A Nguyen, TN Taqi, MA Abraham, MG Janardhan, V Shaltoni, H Novakovic, R Chen, PR Kaushal, R Nanda, A Issa, MA Nogueira, RG Zaidat, OO AF Linfante, Italo Walker, Gail R. Castonguay, Alicia C. Dabus, Guilherme Starosciak, Amy K. Yoo, Albert J. Abou-Chebl, Alex Britz, Gavin W. Marden, Franklin A. Alvarez, Alexandria Gupta, Rishi Sun, Chun-Huan J. Martin, Coleman Holloway, William E. Mueller-Kronast, Nils English, Joey D. Malisch, Tim W. Bozorgchami, Hormozd Xavier, Andrew Rai, Ansaar T. Froehler, Michael T. Badruddin, Aamir Nguyen, Thanh N. Taqi, M. Asif Abraham, Michael G. Janardhan, Vallabh Shaltoni, Hashem Novakovic, Roberta Chen, Peng R. Kaushal, Ritesh Nanda, Ashish Issa, Mohammad A. Nogueira, Raul G. Zaidat, Osama O. TI Predictors of Mortality in Acute Ischemic Stroke Intervention Analysis of the North American Solitaire Acute Stroke Registry SO STROKE LA English DT Article DE carotid artery, internal; intracranial hemorrhages; mortality; stroke; thrombectomy ID MECHANICAL THROMBECTOMY; ENDOVASCULAR TREATMENT; ANTERIOR CIRCULATION; RANDOMIZED-TRIAL; MERCI; REVASCULARIZATION; OCCLUSIONS; RETRIEVER; TANDEM AB Background and Purpose-Failure to recanalize predicts mortality in acute ischemic stroke. In the North American Solitaire Acute Stroke registry, we investigated parameters associated with mortality in successfully recanalized patients. Methods-Logistic regression was used to evaluate baseline characteristics and recanalization parameters for association with 90-day mortality. A multivariable model was developed based on backward selection with retention criteria of P < 0.05 from factors with at least marginal significance (P = 0.10), then refit to minimize the number of excluded cases (missing data). Results-Successfully recanalized patients had lower mortality (25.2% [59/234] versus 46.9% [38/81] P < 0.001). There was no difference in symptomatic intracranial hemorrhage between patients with successful versus failed recanalization (9% [21/234] versus 14% [11/79]; P = 0.205). However, mortality was significantly higher in patients with symptomatic intracranial hemorrhage (72% [23/32] versus 26% [73/281]; P < 0.001). Proximal occlusion (internal carotid artery or vertebrobasilar), initial National Institutes of Health Stroke Scale = 18, use of rescue therapy (P < 0.05), and 3+ passes (P < 0.10) were associated with mortality in recanalized patients. In the multivariate model with good predictive power (c index = 0.72), proximal occlusion, initial National Institutes of Health Stroke Scale = 18, and use of rescue therapy remained significant independent predictors of 90-day mortality. Conclusions-Failure to recanalize and presence of symptomatic intracranial hemorrhage resulted in increased mortality. Despite successful recanalization, proximal occlusion, high National Institutes of Health Stroke Scale, and need for rescue therapy were predictors of mortality. C1 [Linfante, Italo; Dabus, Guilherme; Alvarez, Alexandria] Baptist Hosp Miami, Miami Cardiac & Vasc Inst, Miami, FL 33139 USA. [Linfante, Italo; Walker, Gail R.; Dabus, Guilherme; Starosciak, Amy K.; Alvarez, Alexandria; English, Joey D.] Baptist Hosp Miami, Ctr Neurosci, Miami, FL 33139 USA. [Yoo, Albert J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Britz, Gavin W.] Methodist Neurol Inst, Houston, TX USA. [Abou-Chebl, Alex] Baptist Hlth Louisville, Louisville, KY USA. [Marden, Franklin A.; Malisch, Tim W.] Alexian Bros Med Ctr, Elk Grove Village, IL USA. [Castonguay, Alicia C.; Issa, Mohammad A.; Zaidat, Osama O.] Med Coll Wisconsin, Froedtert Hosp, Milwaukee, WI 53226 USA. [Gupta, Rishi; Sun, Chun-Huan J.; Nogueira, Raul G.] Emory Univ, Sch Med, Atlanta, GA USA. [Mueller-Kronast, Nils] Delray Med Ctr, Delray Beach, FL USA. [English, Joey D.] Calif Pacific Med Ctr, San Francisco, CA USA. [Bozorgchami, Hormozd] Oregon Hlth & Sci, Portland, OR USA. [Xavier, Andrew] Wayne State Univ, Sch Med, Detroit, MI USA. [Rai, Ansaar T.] West Virginia Univ Hosp, Morgantown, WV USA. [Froehler, Michael T.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Badruddin, Aamir] Provena St Joseph Med Ctr, Joliet, IL USA. [Nguyen, Thanh N.] Boston Med Ctr, Boston, MA USA. [Taqi, M. Asif] Desert Reg Med Ctr, Palm Springs, CA USA. [Abraham, Michael G.] Univ Kansas, Med Ctr, Lawrence, KS 66045 USA. [Janardhan, Vallabh] Texas Stroke Inst, Plano, TX USA. [Shaltoni, Hashem] Baylor Coll Med, Houston, TX 77030 USA. [Novakovic, Roberta] UT Southwestern Med Ctr, Dallas, TX USA. [Chen, Peng R.] Univ Texas, Med Sch Houston, Houston, TX USA. [Kaushal, Ritesh] St Louis Univ, St Louis, MO 63103 USA. [Nanda, Ashish] Univ Missouri, Columbia, MO 65211 USA. RP Linfante, I (reprint author), Baptist Hosp Miami, Miami Cardiac & Vasc Inst, Miami, FL 33139 USA. EM italol@baptisthealth.net FU Penumbra, Inc. FX Dr Linfante is a consultant/speaker/proctor for Covidien and a consultant for Stryker. Dr Dabus is a consultant/speaker/proctor for Covidien/Medtronic and a consultant for Microvention/Terumo. Dr Yoo received a research grant from Penumbra, Inc. Dr Gupta is a consultant/advisory board member of Covidien, Stryker Neurovascular, and Rapid Medical. Dr Gupta also received royalties for UpToDate and is an Associate Editor for the Journal of Neuroimaging. Dr English is a consultant for Stryker Neurovascular, Medtronic, and Silk Road Medical. Dr Malisch is a member of Data and Safety Monitoring Board (DSMB) for the Solitaire With the Intention for Thrombectomy (SWIFT) trial, is a Central Empowered Committee member for the Stryker Neurovascular Trevo and Medical Management Versus Medical Management Alone in Wake Up and Late Presenting Strokes (DAWN) trial, and is a shareholder for Covidien and Stryker Neurovascular. Dr. Mueller-Kronast is a consultant for Covidien. Dr. Rai is a consultant/advisory board member of Stryker Neurovascular. Dr Taqi is a consultant for Stryker Neurovascular, Penumbra, and Covidien. Dr Abraham is a consultant of Stryker Neurovascular and on the speaker's bureau for Boehringer Ingelheim. Dr Janardhan is a principal investigator for the Penumbra FIRST study, is a board member for Insera Therapeutics, Inc, and is a member of the DSMB for Penumbra, Inc. Dr Nogueira is a consultant/advisory board member of Covidien, Stryker Neurovascular, and Penumbra. Dr Zaidat is a consultant/advisory board member of Covidien/Medtronic, Stryker, Penumbra, and Codman. The other authors report no conflicts. NR 13 TC 2 Z9 3 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD AUG PY 2015 VL 46 IS 8 BP 2305 EP 2308 DI 10.1161/STROKEAHA.115.009530 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CP6CP UT WOS:000359972200058 PM 26159790 ER PT J AU Janowski, M Wagner, DC Boltze, J AF Janowski, Miroslaw Wagner, Daniel-Christoph Boltze, Johannes TI Stem Cell-Based Tissue Replacement After Stroke Factual Necessity or Notorious Fiction? SO STROKE LA English DT Review DE brain; nerve regeneration; neurons; stem cell transplantation; stroke; tissue engineering; tissue-type plasminogen activator ID ACUTE ISCHEMIC-STROKE; MESENCHYMAL STROMAL CELLS; FOCAL CEREBRAL-ISCHEMIA; NEUROVASCULAR NICHE; FUNCTIONAL RECOVERY; PARKINSONS-DISEASE; ENDOTHELIAL-CELLS; IMPROVE RECOVERY; IN-VITRO; AUTOIMMUNE ENCEPHALOMYELITIS C1 [Janowski, Miroslaw] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Div MR Res, Baltimore, MD USA. [Janowski, Miroslaw] Johns Hopkins Univ, Sch Med, Cellular Imaging Sect, Baltimore, MD USA. [Janowski, Miroslaw] Johns Hopkins Univ, Sch Med, Vasc Biol Program, Inst Cell Engn, Baltimore, MD USA. [Janowski, Miroslaw] Polish Acad Sci, Mossakowski Med Res Ctr, NeuroRepair Dept, Warsaw, Poland. [Janowski, Miroslaw] Polish Acad Sci, Mossakowski Med Res Ctr, Dept Neurosurg, Warsaw, Poland. [Wagner, Daniel-Christoph; Boltze, Johannes] Fraunhofer Inst Cell Therapy & Immunol, Translat Ctr Regenerat Med, Dept Cell Therapy, Leipzig, Germany. [Boltze, Johannes] Harvard Univ, Stroke & Neurovasc Regulat Lab, Massachussets Gen Hosp, Neurosci Ctr,Med Sch,Stroke & Neurovasc Regulat L, Charlestown, MA USA. RP Boltze, J (reprint author), Fraunhofer Inst Cell Therapy & Immunol, Dept Cell Therapy, Perlickstr 1, D-04103 Leipzig, Germany. EM johannes.boltze@izi.fraunhofer.de FU NINDS NIH HHS [R21 NS081544, 1R21NS081544] NR 101 TC 7 Z9 7 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD AUG PY 2015 VL 46 IS 8 BP 2354 EP 2363 DI 10.1161/STROKEAHA.114.007803 PG 10 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CP6CP UT WOS:000359972200070 PM 26106118 ER PT J AU Liebeskind, DS Parsons, MW Wintermark, M Selim, M Molina, CA Lev, MH Gonzalez, RG AF Liebeskind, David S. Parsons, Mark W. Wintermark, Max Selim, Magdy Molina, Carlos A. Lev, Michael H. Gonzalez, Ramon G. TI Computed Tomography Perfusion in Acute Ischemic Stroke Is It Ready for Prime Time? SO STROKE LA English DT Editorial Material DE humans; magnetic resonance angiography; multimodal imaging; stroke; tomography, x-ray computed ID ENDOVASCULAR TREATMENT; RANDOMIZED-TRIAL; TENECTEPLASE; ALTEPLASE C1 [Liebeskind, David S.] Univ Calif Los Angeles, Neurovasc Imaging Res Core, Los Angeles, CA 90095 USA. [Liebeskind, David S.] Univ Calif Los Angeles, Comprehens Stroke Ctr, Geffen Sch Med, Los Angeles, CA 90095 USA. [Liebeskind, David S.] Univ Calif Los Angeles, Dept Neurol, Geffen Sch Med, Div Stroke, Los Angeles, CA 90095 USA. [Parsons, Mark W.] Univ Newcastle, Dept Neurol, John Hunter Hosp, Newcastle, NSW 2300, Australia. [Wintermark, Max] Stanford Univ, Dept Radiol, Neuroradiol Sect, Palo Alto, CA 94304 USA. [Selim, Magdy] Beth Israel Deaconess Med Ctr, Div Stroke & Cerebrovasc Dis, Dept Neurol, Boston, MA 02215 USA. [Molina, Carlos A.] Hosp Valle De Hebron, Dept Neurol, Stroke Unit, Barcelona, Spain. [Lev, Michael H.; Gonzalez, Ramon G.] Massachusetts Gen Hosp, Dept Radiol, Neuroradiol Div, Boston, MA 02114 USA. RP Liebeskind, DS (reprint author), Univ Calif Los Angeles, Dept Neurol, Neurovasc Imaging Res Core, Neurosci Res Bldg,635 Charles E Young Dr S, Los Angeles, CA 90095 USA. EM davidliebeskind@yahoo.com; RGGonzalez@Partners.org FU NINDS NIH HHS [R01NS077706, K24NS072272, R13NS089280] NR 11 TC 2 Z9 2 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD AUG PY 2015 VL 46 IS 8 BP 2364 EP 2367 DI 10.1161/STROKEAHA.115.009179 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CP6CP UT WOS:000359972200071 PM 26159791 ER PT J AU McKinley, SK Phitayakorn, R AF McKinley, Sophia K. Phitayakorn, Roy TI Emotional Intelligence and Simulation SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article DE Emotional intelligence; Simulation; Graduate medical education; ACGME core competencies ID PATIENT-DOCTOR RELATIONSHIP; HIGH-FIDELITY SIMULATION; INTEGRATING SIMULATION; RESIDENCY PROGRAM; MEDICAL-EDUCATION; PROFESSIONALISM; COMMUNICATION; PERFORMANCE; COMPETENCES; TEAMWORK AB Emotional intelligence (EI) is an established concept in the business literature with evidence that it is an important factor in determining career achievement. There is increasing interest in the role that El has in medical training, but it is still a nascent field. This article reviews the El literature most relevant to surgical training and proposes that simulation offers many benefits to the development of El. Although there are many unanswered questions, it is expected that future research will demonstrate the effectiveness of using simulation to develop El within surgery. C1 [McKinley, Sophia K.; Phitayakorn, Roy] Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Sch Med, Boston, MA 02114 USA. RP Phitayakorn, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM rphitayakorn@mgh.harvard.edu OI Phitayakorn, Roy/0000-0002-8327-1484 NR 54 TC 0 Z9 0 U1 1 U2 15 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0039-6109 EI 1558-3171 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD AUG PY 2015 VL 95 IS 4 BP 855 EP + DI 10.1016/j.suc.2015.03.003 PG 14 WC Surgery SC Surgery GA CP4ZL UT WOS:000359891000015 PM 26210976 ER PT J AU Lui, N Wright, C AF Lui, Natalie Wright, Cameron TI Intraoperative Tracheal Injury SO THORACIC SURGERY CLINICS LA English DT Article DE Tracheal injury; Tracheal repair; Esophagectomy complications; Percutaneous tracheostomy complications ID PERCUTANEOUS DILATATIONAL TRACHEOSTOMY; TRACHEOBRONCHIAL INJURY; ESOPHAGECTOMY; MANAGEMENT; LACERATION; REPAIR; PNEUMOPERITONEUM; MEDIASTINOSCOPY; COMPLICATIONS; INTUBATION AB Intraoperative tracheal injury is a rare but potentially devastating complication. Transhiatal esophagectomy should be avoided in patients with proximal esophageal tumors who underwent neoadjuvant therapy, and percutaneous tracheostomy should be avoided in patients with short, thick necks. Early recognition leads to improved outcomes. Patients present with a sudden loss in airway pressure, air leaking into the operative field, or mediastinal and subcutaneous emphysema. Treatment starts with airway control. Primary buttressed repair is recommended, through either a left cervical incision for proximal injuries or a right thoracotomy for distal injuries. Nonoperative management has been used safely in select patients injured during intubation or tracheostomy. C1 [Lui, Natalie; Wright, Cameron] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. RP Wright, C (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM cdwright@partners.org NR 28 TC 2 Z9 2 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1547-4127 J9 THORAC SURG CLIN JI Thorac. Surg. Clin. PD AUG PY 2015 VL 25 IS 3 BP 249 EP + DI 10.1016/j.thorsurg.2015.04.008 PG 7 WC Respiratory System; Surgery SC Respiratory System; Surgery GA CP4ZM UT WOS:000359891100004 PM 26210921 ER PT J AU Lo, JH Bassett, EK Penson, EJN Hoganson, DM Vacanti, JP AF Lo, Justin H. Bassett, Erik K. Penson, Elliot J. N. Hoganson, David M. Vacanti, Joseph P. TI Gas Transfer in Cellularized Collagen-Membrane Gas Exchange Devices SO TISSUE ENGINEERING PART A LA English DT Article ID VASCULAR NETWORK DESIGN; ALVEOLUS-LIKE STRUCTURE; MICROCHANNEL TECHNOLOGIES; LUNG TRANSPLANTATION; BIOARTIFICIAL LUNG; ARTIFICIAL LUNGS; IN-VITRO; RECONSTRUCTION; REGENERATION; EXPERIENCE AB Chronic lower respiratory disease is highly prevalent in the United States, and there remains a need for alternatives to lung transplant for patients who progress to end-stage lung disease. Portable or implantable gas oxygenators based on microfluidic technologies can address this need, provided they operate both efficiently and biocompatibly. Incorporating biomimetic materials into such devices can help replicate native gas exchange function and additionally support cellular components. In this work, we have developed microfluidic devices that enable blood gas exchange across ultra-thin collagen membranes (as thin as 2m). Endothelial, stromal, and parenchymal cells readily adhere to these membranes, and long-term culture with cellular components results in remodeling, reflected by reduced membrane thickness. Functionally, acellular collagen-membrane lung devices can mediate effective gas exchange up to approximate to 288mL/min/m(2) of oxygen and approximate to 685mL/min/m(2) of carbon dioxide, approaching the gas exchange efficiency noted in the native lung. Testing several configurations of lung devices to explore various physical parameters of the device design, we concluded that thinner membranes and longer gas exchange distances result in improved hemoglobin saturation and increases in pO(2). However, in the design space tested, these effects are relatively small compared to the improvement in overall oxygen and carbon dioxide transfer by increasing the blood flow rate. Finally, devices cultured with endothelial and parenchymal cells achieved similar gas exchange rates compared with acellular devices. Biomimetic blood oxygenator design opens the possibility of creating portable or implantable microfluidic devices that achieve efficient gas transfer while also maintaining physiologic conditions. C1 [Lo, Justin H.; Bassett, Erik K.; Penson, Elliot J. N.; Hoganson, David M.; Vacanti, Joseph P.] Massachusetts Gen Hosp, Dept Surg, Ctr Regenerat Med, Boston, MA 02114 USA. [Lo, Justin H.; Vacanti, Joseph P.] Harvard Univ, Sch Med, Boston, MA USA. [Lo, Justin H.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. EM jvacanti@partners.org FU NIH [F32 DK076349-01]; NIH/NIGMS [MSTP T32GM007753] FX The authors gratefully acknowledge support from the NIH (F32 DK076349-01, DMH) and NIH/NIGMS (MSTP T32GM007753, JHL). The authors would like to thank Baoling Liu, Yongqing Li, et al. for use of their blood analyzer, Mary McKee at the PMB Microscopy Core at Massachusetts General Hospital for TEM imaging, and Jessica Melin and the Stanford Microfluidics Foundry for fabrication of the microfluidic molds. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Sciences or the National Institutes of Health. NR 26 TC 2 Z9 2 U1 2 U2 10 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD AUG 1 PY 2015 VL 21 IS 15-16 BP 2147 EP 2155 DI 10.1089/ten.tea.2014.0369 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CP3WF UT WOS:000359812700001 PM 26020102 ER PT J AU Kahle, KT Khanna, AR Alper, SL Adragna, NC Lauf, PK Sun, DD Delpire, E AF Kahle, Kristopher T. Khanna, Arjun R. Alper, Seth L. Adragna, Norma C. Lauf, Peter K. Sun, Dandan Delpire, Eric TI K-Cl cotransporters, cell volume homeostasis, and neurological disease SO TRENDS IN MOLECULAR MEDICINE LA English DT Review DE KCC2; KCC3; NKCC1; WNK-SPAK/OSR1; cell volume; cerebral edema ID CATION-CHLORIDE COTRANSPORTERS; CONDITIONAL MOUSE MODEL; REGULATED ANION CHANNEL; CENTRAL-NERVOUS-SYSTEM; ALANINE-RICH KINASE; CORPUS-CALLOSUM; SENSORY NEUROPATHY; KCL COTRANSPORTER; HEREDITARY MOTOR; FUNCTIONAL-CHARACTERIZATION AB K+-Cl- cotransporters (KCCs) were originally characterized as regulators of red blood cell (RBC) volume. Since then, four distinct KCCs have been cloned, and their importance for volume regulation has been demonstrated in other cell types. Genetic models of certain KCCs, such as KCC3, and their inhibitory WNK-STE20/SPS1-related proline/alanine-rich kinase (SPAK) serine-threonine kinases, have demonstrated the evolutionary necessity of these molecules for nervous system cell volume regulation, structure, and function, and their involvement in neurological disease. The recent characterization of a swelling-activated dephosphorylation mechanism that potently stimulates the KCCs has pinpointed a potentially druggable switch of KCC activity. An improved understanding of WNK/SPAK-mediated KCC cell volume regulation in the nervous system might reveal novel avenues for the treatment of multiple neurological diseases. C1 [Kahle, Kristopher T.; Khanna, Arjun R.] Boston Childrens Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Kahle, Kristopher T.; Khanna, Arjun R.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Kahle, Kristopher T.] Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA 02114 USA. [Alper, Seth L.] Harvard Univ, Sch Med, Div Renal, Boston, MA 02215 USA. [Alper, Seth L.] Harvard Univ, Sch Med, Mol & Vasc Med Div, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Alper, Seth L.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Adragna, Norma C.; Lauf, Peter K.] Wright State Univ, Boonshoft Sch Med, Dept Pharmacol & Toxicol, Dayton, OH 45435 USA. [Lauf, Peter K.] Wright State Univ, Boonshoft Sch Med, Dept Pathol, Dayton, OH 45435 USA. [Sun, Dandan] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15217 USA. [Sun, Dandan] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15213 USA. [Delpire, Eric] Vanderbilt Univ, Sch Med, Dept Anesthesiol, Nashville, TN 37232 USA. RP Kahle, KT (reprint author), Boston Childrens Hosp, Dept Neurosurg, Boston, MA 02114 USA. EM kkahle@enders.tch.harvard.edu; eric.delpire@vanderbilt.edu FU NIGMS NIH HHS [R01 GM074771]; NINDS NIH HHS [R01 NS038118] NR 108 TC 17 Z9 18 U1 1 U2 11 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 2015 VL 21 IS 8 BP 513 EP 523 DI 10.1016/j.molmed.2015.05.008 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA CP4YJ UT WOS:000359888200008 PM 26142773 ER PT J AU Attenberger, U Catana, C Chandarana, H Catalano, OA Friedman, K Schonberg, SA Thrall, J Salvatore, M Rosen, BR Guimaraes, AR AF Attenberger, Ulrike Catana, Ciprian Chandarana, Hersh Catalano, Onofrio A. Friedman, Kent Schonberg, Stefan A. Thrall, James Salvatore, Marco Rosen, Bruce R. Guimaraes, Alexander R. TI Whole-body FDG PET-MR oncologic imaging: pitfalls in clinical interpretation related to inaccurate MR-based attenuation correction SO ABDOMINAL IMAGING LA English DT Review DE PET/MRI; Attenuation correction; Pitfalls ID COMPLETE DISTORTION CORRECTION; RESPIRATORY MOTION CORRECTION; DUAL-MODALITY PET/CT; MAGNETIC-RESONANCE; GEOMETRIC DISTORTION; FIELD INHOMOGENEITIES; SPATIAL MODULATION; F-18-FDG PET/CT; SURFACE COILS; PET/MRI AB Simultaneous data collection for positron emission tomography and magnetic resonance imaging (PET/MR) is now a reality. While the full benefits of concurrently acquiring PET and MR data and the potential added clinical value are still being evaluated, initial studies have identified several important potential pitfalls in the interpretation of fluorodeoxyglucose (FDG) PET/MRI in oncologic whole-body imaging, the majority of which being related to the errors in the attenuation maps created from the MR data. The purpose of this article was to present such pitfalls and artifacts using case examples, describe their etiology, and discuss strategies to overcome them. Using a case-based approach, we will illustrate artifacts related to (1) Inaccurate bone tissue segmentation; (2) Inaccurate air cavities segmentation; (3) Motion-induced misregistration; (4) RF coils in the PET field of view; (5) B0 field inhomogeneity; (6) B1 field inhomogeneity; (7) Metallic implants; (8) MR contrast agents. C1 [Attenberger, Ulrike; Schonberg, Stefan A.] Univ Med Ctr Mannheim, Inst Clin Radiol & Nucl Med, Mannheim, Germany. [Catana, Ciprian; Catalano, Onofrio A.; Rosen, Bruce R.; Guimaraes, Alexander R.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Chandarana, Hersh; Friedman, Kent] NYU, Med Ctr, Dept Radiol, New York, NY 10016 USA. [Catalano, Onofrio A.; Salvatore, Marco] Univ Naples Federico II, SDN IRCCS, Naples, Italy. [Guimaraes, Alexander R.] Oregon Hlth & Sci Univ, Dept Diagnost Imaging, Div Body Imaging, Portland, OR 97239 USA. [Catalano, Onofrio A.; Thrall, James; Guimaraes, Alexander R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Guimaraes, AR (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. EM guimaraa@ohsu.edu RI Salvatore, Marco/K-8083-2016; OI Salvatore, Marco/0000-0001-9734-7702; Chandarana, Hersh/0000-0002-6807-4589 NR 74 TC 5 Z9 5 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-8925 EI 1432-0509 J9 ABDOM IMAGING JI Abdom. Imaging PD AUG PY 2015 VL 40 IS 6 BP 1374 EP 1386 DI 10.1007/s00261-015-0455-3 PG 13 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA CO8QM UT WOS:000359435300005 PM 26025348 ER PT J AU Hope, TA Pampaloni, MH Nakakura, E VanBrocklin, H Slater, J Jivan, S Aparici, CM Yee, J Bergsland, E AF Hope, Thomas A. Pampaloni, Miguel Hernandez Nakakura, Eric VanBrocklin, Henry Slater, James Jivan, Salma Aparici, Carina Mari Yee, Judy Bergsland, Emily TI Simultaneous Ga-68-DOTA-TOC PET/MRI with gadoxetate disodium in patients with neuroendocrine tumor SO ABDOMINAL IMAGING LA English DT Article DE Neuroendocrine tumor; Hepatobiliary agents; PET/MRI; Ga-68 DOTA-TOC ID SOMATOSTATIN RECEPTOR SCINTIGRAPHY; EOB-DTPA; LIVER METASTASES; MRI; PET; CONTRAST; MANAGEMENT; LESIONS; CT AB To evaluate a simultaneous PET/MRI approach to imaging patients with neuroendocrine tumor using a combination of Ga-68-DOTA-TOC as a PET contrast agent and gadoxetate disodium as a hepatobiliary MRI contrast agent. Ten patients with neuroendocrine tumor with known or suspected hepatic disease were imaged using a Ga-68-DOTA-TOC PET/CT immediately followed by a 3.0T time-of-flight PET/MRI, using a combined whole body and liver specific imaging. The presence of lesions and DOTA-TOC avidity were assessed on CT, PET from PET/CT, diffusion weighted imaging, hepatobiliary phase imaging (HBP), and PET from PET/MRI. Maximum standardized uptake values (SUVmax) in hepatic lesions and nodal metastases were compared between PET/CT and PET/MRI, as were detection rates using each imaging approach. A total of 101 hepatic lesions were identified, 47 of which were DOTA-TOC avid and able to be individually measured on both PET/CT and PET/MRI. HBP imaging had a higher sensitivity for detection of hepatic lesions compared to CT or PET (99% vs. 46% and 64%, respectively; p values < 0.001). There was a strong correlation between SUVmax of liver lesions obtained with PET/CT compared to PET/MR imaging (Pearson's correlation = 0.91). For nodal disease, CT had a higher sensitivity compared to whole body MRI (p = 0.015), although PET acquired from PET/MRI detected slightly more lesions compared to PET from PET/CT. A simultaneous PET/MRI using both Ga-68-DOTA-TOC and gadoxetate disodium was successful in whole body staging of patients with neuroendocrine tumor. HBP imaging had an increased detection rate for hepatic metastases. C1 [Hope, Thomas A.; Pampaloni, Miguel Hernandez; VanBrocklin, Henry; Slater, James; Jivan, Salma; Aparici, Carina Mari; Yee, Judy] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Hope, Thomas A.; Yee, Judy] San Francisco VA Med Ctr, Dept Radiol, San Francisco, CA USA. [Nakakura, Eric] Univ Calif San Francisco, Dept Surg, Div Surg Oncol, San Francisco, CA 94143 USA. [Bergsland, Emily] Univ Calif San Francisco, Dept Med, Div Hematol Oncol, San Francisco, CA 94143 USA. RP Hope, TA (reprint author), Univ Calif San Francisco, Dept Radiol & Biomed Imaging, 505 Parnassus Ave 0628, San Francisco, CA 94143 USA. EM thomas.hope@ucsf.edu FU Wylie J. Dodds Research Award, Society of Abdominal Radiology, GE Healthcare FX Grant support from Wylie J. Dodds Research Award, Society of Abdominal Radiology, GE Healthcare. NR 19 TC 7 Z9 7 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-8925 EI 1432-0509 J9 ABDOM IMAGING JI Abdom. Imaging PD AUG PY 2015 VL 40 IS 6 BP 1432 EP 1440 DI 10.1007/s00261-015-0409-9 PG 9 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA CO8QM UT WOS:000359435300010 PM 25820755 ER PT J AU Iyer, VR Hedgire, SS Hoskote, SS Borczuk, D Harisinghani, MG AF Iyer, Veena R. Hedgire, Sandeep S. Hoskote, Sumedh S. Borczuk, David Harisinghani, Mukesh G. TI Retrospective cohort study of portacaval lymphadenopathy identified on multidetector CT and implications for follow-up SO ABDOMINAL IMAGING LA English DT Article DE Portacaval lymph nodes; Cirrhosis; Viral hepatitis; Incidental lymphadenopathy ID ABDOMINAL LYMPH-NODES; CIRRHOSIS; LIVER; ULTRASOUND; CRITERIA; RISK AB Portacaval lymphadenopathy (PCLA) is common in cirrhosis and chronic viral hepatitis and is frequently an incidental finding on abdominal CT scans. We aimed to detect the incidence of malignancy in organs drained by portacaval nodes in patients with PCLA associated with cirrhosis or chronic viral hepatitis, or incidentally detected PCLA. We searched CT reports from 2005 to 2007 for the phrases "periportal node" and "portacaval node." MDCTs of patients with portacaval nodes a parts per thousand yen10 mm in maximal short-axis size on contrast-enhanced MDCTs, were included. Records were reviewed for presence of malignancy, liver metastases, chronic viral hepatitis, and cirrhosis. Clinical or imaging follow-up a parts per thousand yen6 months was performed to detect if malignancy developed in organs drained by portacaval nodes in patients with incidental PCLA, cirrhosis, or chronic viral hepatitis. 479 patients met inclusion criteria [298 males (62%), mean age 61.4 years]. In 285 (59.5%) patients, PCLA was explained by local pathology or systemic lymphadenopathy. PCLA was incidental in 146 (30.5%) patients. Of these, 112 (76.7%) had a parts per thousand yen6 months of follow-up (median 26 months). No patient with incidental PCLA developed malignancy in organs drained by these nodes. Cirrhosis or chronic viral hepatitis was present in 48 (10.0%) patients. Of these, 42 (87.5%) had a parts per thousand yen6 months follow-up (median 28 months), and only 1 patient developed cholangiocarcinoma (positive predictive value 2.4%). Development of malignancy is rare in patients with PCLA, either incidental or secondary to cirrhosis or chronic viral hepatitis. Our study suggests that no follow-up of PCLA is required in these settings. C1 [Iyer, Veena R.; Hedgire, Sandeep S.; Borczuk, David; Harisinghani, Mukesh G.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Iyer, Veena R.] Univ Minnesota, Dept Radiol, Minneapolis, MN 55455 USA. [Hoskote, Sumedh S.] Mayo Clin, Dept Med, Div Pulm & Crit Care Med, Rochester, MN 55905 USA. RP Iyer, VR (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM iyerx063@umn.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 0942-8925 EI 1432-0509 J9 ABDOM IMAGING JI Abdom. Imaging PD AUG PY 2015 VL 40 IS 6 BP 1481 EP 1486 DI 10.1007/s00261-014-0328-1 PG 6 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA CO8QM UT WOS:000359435300017 PM 25516214 ER PT J AU Baheti, AD Tirumani, SH Sewatkar, R Sachin, SS Shinagare, AB Ramaiya, NH AF Baheti, Akshay D. Tirumani, Sree Harsha Sewatkar, Rani Sachin, Saboo S. Shinagare, Atul B. Ramaiya, Nikhil H. TI MDCT of extranodal mantle cell lymphoma: a single institute experience SO ABDOMINAL IMAGING LA English DT Article DE Mantle cell lymphoma; Extranodal; Gastrointestinal; GI; CT ID POSITRON-EMISSION-TOMOGRAPHY; GASTROINTESTINAL-TRACT; IMAGING FINDINGS; FEATURES; CT; INVOLVEMENT; POLYPOSIS; SPECTRUM; LESIONS AB To study the pattern of extranodal and particularly gastrointestinal (GI) involvement of mantle cell lymphoma (MCL) on MDCT In this IRB-approved, HIPAA compliant retrospective study, MDCT features of 78 patients (62 males and 16 females, mean age 57 years) with MCL including 28 patients at presentation were reviewed. Clinical and histopathological (blastoid vs. non-blastoid) data were noted from medical records. Extranodal involvement was present in overall 51/78 patients on CT (65%), 18/28 (64%) patients at presentation. Spleen (21/78-27%) and bowel (19/78-24%) were the most common sites of extranodal involvement by MCL on imaging, followed by lungs (10/78-13%) and skin/subcutaneous tissue (9/78-12%). Bowel involvement was either in the form of endophytic polypoidal lesions (n = 11, mean size 3.1 cm), as focal mild bowel wall thickening (n = 5, mean thickness 1.4 cm), or as combination of the two (n = 3). Blastoid histology was present in 14/78 (24%) patients and was statistically associated with skin/subcutaneous involvement (p < 0.05; Fisher's exact t test). Median follow-up was 72 months during which 21 patients died with median survival of 48 months (26 months for blastoid histology vs. 47 months for non-blastoid histology). There was no statistical correlation between sites of involvement and survival. MCL has a predilection for extranodal disease, predominantly involving the spleen, bowel, lungs, and subcutaneous tissue. GI involvement on CT is in the form of endoluminal polypoidal lesions and mild bowel wall thickening. Skin/subcutaneous involvement was statistically more common with blastoid histology in our study. C1 [Baheti, Akshay D.; Tirumani, Sree Harsha; Sachin, Saboo S.; Shinagare, Atul B.; Ramaiya, Nikhil H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Baheti, Akshay D.; Tirumani, Sree Harsha; Sewatkar, Rani; Sachin, Saboo S.; Shinagare, Atul B.; Ramaiya, Nikhil H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Baheti, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM akshaybaheti@gmail.com NR 30 TC 3 Z9 3 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-8925 EI 1432-0509 J9 ABDOM IMAGING JI Abdom. Imaging PD AUG PY 2015 VL 40 IS 6 BP 1693 EP 1699 DI 10.1007/s00261-015-0389-9 PG 7 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA CO8QM UT WOS:000359435300037 PM 25724714 ER PT J AU Tian, F Hayano, K Kambadakone, AR Sahani, DV AF Tian, Fang Hayano, Koichi Kambadakone, Avinash R. Sahani, Dushyant V. TI Response assessment to neoadjuvant therapy in soft tissue sarcomas: using CT texture analysis in comparison to tumor size, density, and perfusion SO ABDOMINAL IMAGING LA English DT Article DE Soft tissue sarcomas; Computed tomography texture analysis; CT perfusion; Heterogeneity; Treatment response ID CELL LUNG-CANCER; HEPATOCELLULAR-CARCINOMA; PATHOLOGICAL RESPONSE; COLORECTAL-CANCER; RADIATION-THERAPY; BLOOD-FLOW; CHEMOTHERAPY; SURVIVAL; HETEROGENEITY; RECIST AB Purpose: To evaluate the role of computed tomography (CT) texture analysis in assessing response of soft tissue sarcoma (STS) treated with neoadjuvant bevacizumab (BVZ) plus radiotherapy in comparison to tumor size, density, and perfusion. Methods: In the phase II clinical trial, 20 patients with STSs received BVZ alone for 2 weeks followed by BVZ plus radiotherapy for 6 weeks prior to surgery. All patients received CT perfusion at baseline, 2 and 8 weeks after the therapy, and tumor blood flow (BF) was measured. In contrast enhanced CT image at the arterial peak enhancement time, mean of positive pixels (MPP) was measured as a texture parameter using texture analysis software, and tumor size and density were also measured. The percent changes of these parameters were compared with pathological response on surgical specimen. Results: After 2 weeks of the therapy, MPP and BF decreased by 10.42% and 20.08%, while changes of tumor size and density were not obvious. After 8 weeks, MPP, BF, and density decreased by 29.2% (p = 0.03), 53.2% (p = 0.001), and 30.41% (p = 0.005), respectively, without a significant change in size. The percent change of MPP after 8 weeks had a significant correlation with tumor necrosis in surgical specimen (r = -0.801, p < 0.001), whereas those of size, density, and BF did not. The receiver-operating characteristic analysis demonstrated that the percent change of MPP < -35.36% was an optimal cut-off value to differentiate pathological responders. Conclusion: The change of MPP is the best biomarker for the treatment response in STS. C1 [Tian, Fang; Hayano, Koichi; Kambadakone, Avinash R.; Sahani, Dushyant V.] Harvard Univ, Sch Med, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Tian, Fang; Hayano, Koichi; Kambadakone, Avinash R.; Sahani, Dushyant V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tian, Fang] Shanghai Univ Tradit Chinese Med, Yueyang Hosp Integrated Tradit Chinese & Western, Dept Radiol, Shanghai 200437, Peoples R China. RP Sahani, DV (reprint author), Harvard Univ, Sch Med, Div Abdominal Imaging & Intervent, 55 Fruit St White 270, Boston, MA 02114 USA. EM dsahani@partners.org NR 34 TC 3 Z9 3 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-8925 EI 1432-0509 J9 ABDOM IMAGING JI Abdom. Imaging PD AUG PY 2015 VL 40 IS 6 BP 1705 EP 1712 DI 10.1007/s00261-014-0318-3 PG 8 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA CO8QM UT WOS:000359435300039 PM 25526682 ER PT J AU Butros, SR McCarthy, CJ Karaosmanoglu, AD Shenoy-Bhangle, AS Arellano, RS AF Butros, Selim Reha McCarthy, Colin James Karaosmanoglu, Ali Devrim Shenoy-Bhangle, Anuradha S. Arellano, Ronald S. TI Feasibility and effectiveness of image-guided percutaneous biopsy of the urinary bladder SO ABDOMINAL IMAGING LA English DT Article DE Bladder biopsy; Transitional cell carcinoma; Malignant tumor of urinary bladder; CT-guided biopsy; Pathology ID ASYMPTOMATIC MICROSCOPIC HEMATURIA; DEEP PELVIC LESIONS; FLEXIBLE CYSTOSCOPY; VIRTUAL CYSTOSCOPY; PRACTICE POLICY; GUIDELINES; MANAGEMENT; CYTOLOGY; MARKERS; CANCER AB To evaluate the indications, technique, results, and complications of image-guided percutaneous biopsy of the urinary bladder. This retrospective study included 15 patients (10 male, 5 female) who underwent image-guided percutaneous biopsy of the urinary bladder between January 1999 and December 2013. The medical records, imaging studies, procedural details, and long-term follow-up of each patient were reviewed in detail to assess the feasibility of percutaneous bladder biopsy. Ten patients had focal bladder masses and 5 patients had asymmetric or diffuse bladder wall thickening. Eleven patients had either negative or unsatisfactory cystoscopies prior to the biopsy. Percutaneous biopsies were performed under computed tomography guidance in 12 patients and ultrasound in 3 patients. All procedures were technically successful and there were no procedural complications. Malignancy was confirmed in 8 patients, among whom 6 had transitional cell carcinoma, 1 cervical cancer, and 1 prostate cancer metastasis. Seven patients had a benign diagnosis, including 3 that were later confirmed by pathology following surgery and 2 patients with a false-negative result. The overall sensitivity was 80% and accuracy was 87%. Image-guided percutaneous biopsy of the urinary bladder is a safe and technically feasible procedure with a high sensitivity and accuracy rate. Although image-guided bladder biopsy is an uncommon procedure, it should be considered in selected cases when more traditional methods of tissue sampling are either not possible or fail to identify abnormalities detected by cross-sectional imaging. C1 [Butros, Selim Reha; McCarthy, Colin James; Karaosmanoglu, Ali Devrim; Shenoy-Bhangle, Anuradha S.; Arellano, Ronald S.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Arellano, RS (reprint author), Massachusetts Gen Hosp, Dept Radiol, White 270,55 Fruit St, Boston, MA 02114 USA. EM rarellano@mgh.harvard.edu NR 19 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-8925 EI 1432-0509 J9 ABDOM IMAGING JI Abdom. Imaging PD AUG PY 2015 VL 40 IS 6 BP 1838 EP 1842 DI 10.1007/s00261-015-0356-5 PG 5 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA CO8QM UT WOS:000359435300054 PM 25875861 ER PT J AU Wood, MJ Tirumani, SH Sweeney, C Ramaiya, NH Howard, SA AF Wood, Monica J. Tirumani, Sree Harsha Sweeney, Christopher Ramaiya, Nikhil H. Howard, Stephanie A. TI Approach to risk stratification in testicular germ cell tumors: a primer for radiologists SO ABDOMINAL IMAGING LA English DT Article DE Testicular germ cell tumors; Testicular cancer imaging; Risk stratification; Prognosis ID POSITRON-EMISSION-TOMOGRAPHY; EUROPEAN CONSENSUS CONFERENCE; LYMPH-NODE METASTASES; STAGE-I SEMINOMA; SURVEILLANCE FOLLOWING ORCHIECTOMY; CANCER STUDY-GROUP; TESTIS CANCER; FDG-PET; COMPUTED-TOMOGRAPHY; RESIDUAL MASSES AB Oncologists increasingly exploit differences in testicular germ cell tumors to deliver more personalized treatment. Imaging is essential in this process, aiding in the selection of risk-stratified management strategies. Consideration of relevant prognostic factors strengthens image interpretation, allowing for a more nuanced radiographic evaluation. This paper uses a clinically focused, stage-by-stage approach to delineate the risk factors for relapse and metastasis that radiologists should consider during staging, response assessment, and surveillance. C1 [Wood, Monica J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Tirumani, Sree Harsha; Ramaiya, Nikhil H.; Howard, Stephanie A.] Harvard Univ, Dept Imaging, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. [Tirumani, Sree Harsha; Ramaiya, Nikhil H.; Howard, Stephanie A.] Harvard Univ, Dept Radiol, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Sweeney, Christopher] Harvard Univ, Dept Med Oncol, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. [Sweeney, Christopher] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Wood, MJ (reprint author), Harvard Univ, Sch Med, 25 Shattuck St, Boston, MA 02115 USA. EM mwood9@partners.org NR 92 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0942-8925 EI 1432-0509 J9 ABDOM IMAGING JI Abdom. Imaging PD AUG PY 2015 VL 40 IS 6 BP 1871 EP 1886 DI 10.1007/s00261-014-0304-9 PG 16 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA CO8QM UT WOS:000359435300058 PM 25432868 ER PT J AU Jenkins, TC Knepper, BC Moore, SJ Saveli, CC Pawlowski, SW Perlman, DM McCollister, BD Burman, WJ AF Jenkins, Timothy C. Knepper, Bryan C. Moore, S. Jason Saveli, Carla C. Pawlowski, Sean W. Perlman, Daniel M. McCollister, Bruce D. Burman, William J. TI Microbiology and Initial Antibiotic Therapy for Injection Drug Users and Non-Injection Drug Users with Cutaneous Abscesses in the Era of Community-associated Methicillin-resistant Staphylococcus aureus SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID SOFT-TISSUE INFECTIONS; ACUTE BACTERIAL SKIN; EMERGENCY-DEPARTMENT AB ObjectivesThe incidence of cutaneous abscesses has increased markedly since the emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). Injection drug use is a risk factor for abscesses and may affect the microbiology and treatment of these infections. In a cohort of patients hospitalized with cutaneous abscesses in the era of CA-MRSA, the objectives were to compare the microbiology of abscesses between injection drug users and non-injection drug users and evaluate antibiotic therapy started in the emergency department (ED) in relation to microbiologic findings and national guideline treatment recommendations. MethodsThis was a secondary analysis of two published retrospective cohorts of patients requiring hospitalization for acute bacterial skin infections between January 1, 2007, and May 31, 2012, in seven academic and community hospitals in Colorado. In the subgroup of patients with cutaneous abscesses, microbiologic findings and the antibiotic regimens started in the ED were compared between injection drug users and non-injection drug users. Antibiotic regimens involving multiple agents, lack of activity against MRSA, or an agent with broad Gram-negative activity were classified as discordant with Infectious Diseases Society of America (IDSA) guideline treatment recommendations. ResultsOf 323 patients with cutaneous abscesses, 104 (32%) occurred in injection drug users. Among the 235 cases where at least one microorganism was identified by culture, S.aureus was identified less commonly among injection drug users compared with non-injection drug users (55% vs. 75%, p=0.003), with similar patterns observed for MRSA (33% vs. 47%, p=0.054) and methicillin-susceptible S.aureus (17% vs. 26%, p=0.11). In contrast to S.aureus, streptococcal species (53% vs. 25%, p<0.001) and anaerobic organisms (29% vs. 10%, p<0.001) were identified more commonly among injection drug users. Of 88 injection drug users and 186 non-injection drug users for whom antibiotics were started in the ED, the antibiotic regimens were discordant with IDSA guideline recommendations in 47 (53%) and 101 (54%), respectively (p=0.89). In cases where MRSA was ultimately identified, the antibiotic regimen started in the ED lacked activity against this pathogen in 14% of cases. ConclusionsCompared with non-injection drug users, cutaneous abscesses in injection drug users were less likely to involve S.aureus, including MRSA, and more likely to involve streptococci and anaerobes; however, MRSA was common in both groups. Antibiotic regimens started in the ED were discordant with national guidelines in over half of cases and often lacked activity against MRSA when this pathogen was present. C1 [Jenkins, Timothy C.; Burman, William J.] Denver Hlth, Dept Med, Denver, CO 80230 USA. [Jenkins, Timothy C.; Burman, William J.] Denver Hlth, Div Infect Dis, Denver, CO USA. [Knepper, Bryan C.] Denver Hlth, Dept Patient Safety & Qual, Denver, CO USA. [Burman, William J.] Denver Hlth, Denver Publ Hlth, Denver, CO USA. [Jenkins, Timothy C.; Saveli, Carla C.; McCollister, Bruce D.; Burman, William J.] Univ Colorado, Sch Med, Dept Med, Div Infect Dis, Aurora, CO USA. [Moore, S. Jason] Vail Valley Med Ctr, Dept Trauma & Crit Care Serv, Vail, CO USA. [Pawlowski, Sean W.] Colorado Infect Dis Associates, Denver, CO USA. [Perlman, Daniel M.] Porter Adventist Med Ctr, Dept Med, Denver, CO USA. [McCollister, Bruce D.] Denver Vet Affairs Med Ctr, Dept Med, Div Infect Dis, Denver, CO USA. RP Jenkins, TC (reprint author), Denver Hlth, Dept Med, Denver, CO 80230 USA. EM timothy.jenkins@dhha.org FU NIAID NIH HHS [K23 AI099082] NR 13 TC 0 Z9 1 U1 1 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 2015 VL 22 IS 8 BP 993 EP 997 DI 10.1111/acem.12727 PG 5 WC Emergency Medicine SC Emergency Medicine GA CO8OE UT WOS:000359428400015 PM 26202847 ER PT J AU Wang, ML Kuchiba, A Ogino, S AF Wang, Molin Kuchiba, Aya Ogino, Shuji TI A Meta-Regression Method for Studying Etiological Heterogeneity Across Disease Subtypes Classified by Multiple Biomarkers SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE causal inference; genomics; heterogeneity test; molecular diagnosis; omics; transdisciplinary epidemiology ID MOLECULAR PATHOLOGICAL EPIDEMIOLOGY; TUMOR MICROSATELLITE INSTABILITY; ISLAND METHYLATOR PHENOTYPE; COLORECTAL-CANCER RISK; LIFE-STYLE FACTORS; MLH1-93G-GREATER-THAN-A PROMOTER POLYMORPHISM; COLON-CANCER; CIGARETTE-SMOKING; BRAF MUTATIONS; ALCOHOL-CONSUMPTION AB In interdisciplinary biomedical, epidemiologic, and population research, it is increasingly necessary to consider pathogenesis and inherent heterogeneity of any given health condition and outcome. As the unique disease principle implies, no single biomarker can perfectly define disease subtypes. The complex nature of molecular pathology and biology necessitates biostatistical methodologies to simultaneously analyze multiple biomarkers and subtypes. To analyze and test for heterogeneity hypotheses across subtypes defined by multiple categorical and/or ordinal markers, we developed a meta-regression method that can utilize existing statistical software for mixed-model analysis. This method can be used to assess whether the exposure-subtype associations are different across subtypes defined by 1 marker while controlling for other markers and to evaluate whether the difference in exposure-subtype association across subtypes defined by 1 marker depends on any other markers. To illustrate this method in molecular pathological epidemiology research, we examined the associations between smoking status and colorectal cancer subtypes defined by 3 correlated tumor molecular characteristics (CpG island methylator phenotype, microsatellite instability, and the B-Raf protooncogene, serine/threonine kinase (BRAF), mutation) in the Nurses' Health Study (1980-2010) and the Health Professionals Follow-up Study (1986-2010). This method can be widely useful as molecular diagnostics and genomic technologies become routine in clinical medicine and public health. C1 [Wang, Molin; Kuchiba, Aya; Ogino, Shuji] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Wang, Molin] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Wang, Molin] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Wang, Molin; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA USA. [Kuchiba, Aya] Natl Canc Ctr, Ctr Res Adm & Support, Div Biostat, Tokyo 104, Japan. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Wang, ML (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Biostat, Sch Med, 677 Huntington Ave, Boston, MA 02115 USA. EM stmow@channing.harvard.edu FU US National Institutes of Health [R01 CA151993, R35 CA197735, P01 CA87969, UM1 CA186107, P01 CA55075, UM1 CA167552, P50 CA127003]; Paula and Russell Agrusa Fund for Colorectal Cancer Research; Dana-Farber Cancer Institute FX This work was supported by US National Institutes of Health grants (R01 CA151993 and R35 CA197735 to S.O., P01 CA87969 to S. E. Hankinson, UM1 CA186107 to M. J. Stampfer, P01 CA55075 and UM1 CA167552 to W. C. Willett, and P50 CA127003 to C. S. Fuchs); grants from The Paula and Russell Agrusa Fund for Colorectal Cancer Research (to C. S. Fuchs); and the Friends of the Dana-Farber Cancer Institute (to S. O.). NR 62 TC 9 Z9 9 U1 0 U2 7 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 2015 VL 182 IS 3 BP 263 EP 270 DI 10.1093/aje/kwv040 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CO7BC UT WOS:000359311500009 PM 26116215 ER PT J AU Lam, S Gupta, R Levental, M Yu, E Curtin, HD Forghani, R AF Lam, S. Gupta, R. Levental, M. Yu, E. Curtin, H. D. Forghani, R. TI Optimal Virtual Monochromatic Images for Evaluation of Normal Tissues and Head and Neck Cancer Using Dual-Energy CT SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; COMPUTED-TOMOGRAPHY; OPTIMIZATION; ARTIFACTS; CARTILAGE; LARYNGEAL; IMPROVE AB BACKGROUND AND PURPOSE: Dual-energy CT is not used routinely for evaluation of the head and neck, and there is no consensus on the optimal virtual monochromatic image energies for evaluating normal tissues or head and neck cancer. We performed a quantitative evaluation to determine the optimal virtual monochromatic images for visualization of normal tissues, head and neck squamous cell carcinoma, and lymphadenopathy. MATERIALS AND METHODS: Dual-energy CT scans from 10 healthy patients and 30 patients with squamous cell carcinoma were evaluated at different virtual monochromatic energy levels ranging from 40 to 140 keV. The signal-to-noise ratios of muscles at 6 different levels, glands (parotid, sublingual, submandibular, and thyroid), 30 tumors, and 17 metastatic lymph nodes were determined as measures of optimal image quality. Lesion attenuation and contrast-to-noise ratios (compared with those of muscle) were evaluated to assess lesion conspicuity. RESULTS: The optimal signal-to-noise ratio for all the tissues was at 65 keV (P < .0001). However, tumor attenuation (P < .0001), attenuation difference between tumor and muscles (P = .03), and lesion contrast-to-noise ratios (P < .0001) were highest at 40 keV. CONCLUSIONS: The optimal image signal-to-noise ratio is at 65 keV, but tumor conspicuity compared with that of muscle is greatest at 40 keV. Optimal evaluation of the neck may be best achieved by a multiparametric approach, with 65-keV virtual monochromatic images providing the best overall image quality and targeted use of 40-keV virtual monochromatic images for tumor evaluation. C1 [Lam, S.; Levental, M.; Forghani, R.] McGill Univ, Jewish Gen Hosp, Dept Radiol, Montreal, PQ H3T 1E2, Canada. [Gupta, R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Yu, E.] Univ Toronto, Univ Hlth Network, Princess Margaret Hosp, Joint Dept Med Imaging, Toronto, ON, Canada. [Curtin, H. D.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Forghani, R (reprint author), McGill Univ, Jewish Gen Hosp, Dept Radiol, Room C-212-1,3755 Cote Ste Catherine Rd, Montreal, PQ H3T 1E2, Canada. EM rforghani@jgh.mcgill.ca FU American Society of Head and Neck Radiology FX Abstract previously presented at: Annual Meeting of the American Society of Head and Neck Radiology, September 10-14, 2014; Seattle, Washington. S.L. received the American Society of Head and Neck Radiology's Radiologist-in-Training award. NR 22 TC 5 Z9 5 U1 1 U2 5 PU AMER SOC NEURORADIOLOGY PI DENVILLE PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA SN 0195-6108 EI 1936-959X J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD AUG PY 2015 VL 36 IS 8 BP 1518 EP 1524 DI 10.3174/ajnr.A4314 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CP1TC UT WOS:000359657400023 PM 26021623 ER PT J AU Janech, MG Rodgers, JL Arthur, JM Velez, JCQ AF Janech, Michael G. Rodgers, Jessalyn L. Arthur, John M. Velez, Juan Carlos Q. TI Letter to the editor: "Concern regarding quantification of urinary nephrin by a commercially available ELISA" SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Letter ID SPONTANEOUSLY HYPERTENSIVE-RATS; INJURY C1 [Janech, Michael G.; Rodgers, Jessalyn L.; Arthur, John M.; Velez, Juan Carlos Q.] Med Univ S Carolina, Div Nephrol, Charleston, SC 29425 USA. [Arthur, John M.; Velez, Juan Carlos Q.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC USA. [Arthur, John M.] Univ Arkansas Med Sci, Div Nephrol, Little Rock, AR 72205 USA. RP Janech, MG (reprint author), Med Univ S Carolina, Div Nephrol, 96 Jonathan Lucas St,829 Clinical Sci Bldg, Charleston, SC 29425 USA. EM janechmg@musc.edu RI Velez, Juan Carlos/N-3782-2016; OI Janech, Michael/0000-0002-3202-4811 NR 6 TC 1 Z9 1 U1 0 U2 1 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 2015 VL 309 IS 3 BP F269 EP F270 DI 10.1152/ajprenal.00159.2015 PG 2 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA CP2TZ UT WOS:000359731400010 PM 26357486 ER PT J AU Subathra, M Korrapati, M Howell, LA Arthur, JM Shayman, JA Schnellmann, RG Siskind, LJ AF Subathra, Marimuthu Korrapati, Midhun Howell, Lauren A. Arthur, John M. Shayman, James A. Schnellmann, Rick G. Siskind, Leah J. TI Kidney glycosphingolipids are elevated early in diabetic nephropathy and mediate hypertrophy of mesangial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE glycosphingolipids; kidney; diabetic nephropathy; hypertrophy; mesangial cells ID HIGH GLUCOSE; GLUCOSYLCERAMIDE SYNTHASE; INSULIN SENSITIVITY; RENAL-DISEASE; UP-REGULATION; PROLIFERATION; MICE; FIBRONECTIN; METABOLISM; INHIBITION AB Glycosphingolipids (GSLs) play a role in insulin resistance and diabetes, but their role in diabetic nephropathy (DN) has received limited attention. We used 9- and 17-wk-old nondiabetic db/m and diabetic db/db mice to examine the role of GSLs in DN. Cerebrosides or monoglycosylated GSLs [hexosylceramides (HexCers); glucosyl- and galactosylceramides] and lactosylceramide (LacCers) were elevated in db/db mouse kidney cortices, specifically in glomeruli, and also in urine. In our recent paper (25), we observed that the kidneys exhibited glomerular hypertrophy and proximal tubular vacuolization and increased fibrosis markers at these time points. Mesangial cells contribute to hyperglycemia- induced glomerular hypertrophy in DN. Hyperglycemic culture conditions, similar to that present in diabetes, were sufficient to elevate mesangial cell HexCers and increase markers of fibrosis, extracellular matrix proteins, and cellular hypertrophy. Inhibition of glucosylceramide synthase or lowering glucose levels decreased markers of fibrosis and extracellular matrix proteins and reversed mesangial cell hypertrophy. Hyperglycemia increased phosphorylated (p)SMAD3 and pAkt levels and reduced phosphatase and tensin homolog levels, which were reversed with glucosylceramide synthase inhibition. These data suggest that inhibition of glucosylceramide synthase reversed mesangial cell hypertrophy through decreased pAkt and pSmad3 and increased pathways responsible for protein degradation. Importantly, urinary GSL levels were higher in patients with DN compared with healthy control subjects, implicating a role for these lipids in human DN. Thus, hyperglycemia in type II diabetes leads to renal dysfunction at least in part by inducing accumulation of HexCers and LacCers in mesangial cells, resulting in fibrosis, extracellular matrix production, and hypertrophy. C1 [Subathra, Marimuthu; Siskind, Leah J.] Univ Louisville, Dept Pharmacol & Toxicol, James Graham Brown Canc Ctr, Louisville, KY 40292 USA. [Korrapati, Midhun; Schnellmann, Rick G.] Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA. [Howell, Lauren A.] Florida State Univ, Dept Biomed Sci, Tallahassee, FL 32306 USA. [Arthur, John M.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Arthur, John M.] Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. [Shayman, James A.] Univ Michigan, Sch Med, Nephrol Div, Dept Internal Med, Ann Arbor, MI 48109 USA. [Schnellmann, Rick G.] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. RP Siskind, LJ (reprint author), Univ Louisville, Dept Pharmacol & Toxicol, 505 S Hancock St,CTRB 203, Louisville, KY 40292 USA. EM leah.siskind@louisville.edu FU National Institutes of Health (NIH) [P20-RR-17677, R01-DK-093462, R01-DK-101034, R01-GM-084147]; Veterans Administration Merit Review Grant [BX-000851]; Veterans Affairs Research Enhancement Award Program; Lipidomics Shared Resource of the Hollings Cancer Center at the Medical University of South Carolina - NIH Grant [P30-CA-138313] FX This work was supported by National Institutes of Health (NIH) Grants P20-RR-17677 (COBRE in Lipidomics and Pathobiology pilot project), R01-DK-093462 (to L. J. Siskind), R01-DK-101034 (to J. M. Arthur), and R01-GM-084147 (to R. G. Schnellmann), Veterans Administration Merit Review Grant BX-000851 (to R. G. Schnellmann), Veterans Affairs Research Enhancement Award Program pilot project funding (to L. J. Siskind, J. M. Arthur, and R. G. Schnellmann), and the Lipidomics Shared Resource of the Hollings Cancer Center at the Medical University of South Carolina, supported by NIH Grant P30-CA-138313. NR 65 TC 3 Z9 5 U1 0 U2 3 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 2015 VL 309 IS 3 BP F204 EP F215 DI 10.1152/ajprenal.00150.2015 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA CP2TZ UT WOS:000359731400003 PM 26041445 ER PT J AU Gordon, JL Girdler, SS Meltzer-Brody, SE Stika, CS Thurston, RC Clark, CT Prairie, BA Moses-Kolko, E Joffe, H Wisner, KL AF Gordon, Jennifer L. Girdler, Susan S. Meltzer-Brody, Samantha E. Stika, Catherine S. Thurston, Rebecca C. Clark, Crystal T. Prairie, Beth A. Moses-Kolko, Eydie Joffe, Hadine Wisner, Katherine L. TI Depression and Insulin Resistance: Additional Support for the Novel Heuristic Model in Perimenopausal Depression Response SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Letter C1 Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. Northwestern Univ, Dept Obstet Gynecol, Chicago, IL 60611 USA. Northwestern Univ, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Dept Obstet & Gynecol,Allegheny Hlth Network, Pittsburgh, PA USA. Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Gordon, JL (reprint author), Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. FU NICHD NIH HHS [K12 HD055884] NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 2015 VL 172 IS 8 BP 797 EP 797 DI 10.1176/appi.ajp.2015.15030377r PG 1 WC Psychiatry SC Psychiatry GA CO6NZ UT WOS:000359274700025 PM 26234606 ER PT J AU King, TC Upfal, M Gottlieb, A Adamo, P Bernacki, E Kadlecek, CP Jones, JG Humphrey-Carothers, F Rielly, AF Drewry, P Murray, K DeWitt, M Matsubara, J O'Dea, L Balser, J Wrighton-Smith, P AF King, Thomas C. Upfal, Mark Gottlieb, Andrew Adamo, Philip Bernacki, Edward Kadlecek, Chris P. Jones, Jeffrey G. Humphrey-Carothers, Frances Rielly, Albert F. Drewry, Pamela Murray, Kathy DeWitt, Marcie Matsubara, Janet O'Dea, Louis Balser, John Wrighton-Smith, Peter TI T-SPOT.TB Interferon-gamma Release Assay Performance in Healthcare Worker Screening at Nineteen US Hospitals SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE tuberculosis screening; LTBI; conversion; reversion; serial testing ID LATENT TUBERCULOSIS INFECTION; IN-TUBE ASSAY; UNITED-STATES; SKIN-TEST; CHALLENGES; REPRODUCIBILITY; CONVERSIONS; POPULATION; PREVALENCE; DIAGNOSIS AB Rationale: Interferon-gamma release assays have significant advantages over tuberculin skin testing in many clinical situations. However, recent studies have called into question their reliability in serial testing of healthcare workers because of reportedly high rates of positivity and high conversion/reversion rates on retesting. Objectives: To define the performance characteristics of the T-SPOT.TB test, an interferon-gamma release assay, during serial screening programs of healthcare workers at 19 U.S. hospitals. Methods: A total of 42,155 T-SPOT.TB test results from healthcare workers at 19 geographically diverse hospitals obtained for routine tuberculosis screening programs were analyzed to determine the rates of positivity, reversion, and conversion in serial testing data. Measurements and Main Results: In 19,630 evaluable serial pairs from 16,076 healthcare workers, the mean test positivity rate was 2.3% (range, 0.0-27.4%). The mean conversion rate was 0.8% (range, 0.0-2.5%), and the mean reversion rate was 17.6%. Positivity and conversion rates correlated with known tuberculosis risk factors including age and sex. The observed specificity of the T-SPOT.TB test was at least 98.6%. Conclusions: The high concordance and test completion rates in this study suggest that the T-SPOT.TB test is a reliable tool for healthcare worker serial screening. As expected, the observed positivity rates were lower compared with the tuberculin skin test, likely reflecting the higher specificity of this test. Furthermore, the observed rates of conversion were low and significantly correlated with the geographic incidence of tuberculosis. Our findings suggest that the T-SPOT.TB test is an accurate and reliable way to screen healthcare workers. C1 [King, Thomas C.] St Vincent Hosp, Dept Pathol & Lab Med, Worcester, MA 01608 USA. [Upfal, Mark] Detroit Med Ctr, Occupat Hlth Serv, Detroit, MI USA. [Gottlieb, Andrew; Rielly, Albert F.] Massachusetts Gen Hosp, Occupat Hlth Serv, Boston, MA 02114 USA. [Adamo, Philip] UMass Mem Hlth Care, Dept Med Employee Hlth Serv & Occupat Injury Care, Worcester, MA USA. [Bernacki, Edward] Johns Hopkins Univ, Sch Med, Div Occupat Med, Baltimore, MD USA. [Kadlecek, Chris P.] St Davids Med Ctr, Occupat Hlth Serv, Austin, TX USA. [Jones, Jeffrey G.] St Francis Hosp, Occupat Hlth, Indianapolis, IN USA. [Humphrey-Carothers, Frances] Johns Hopkins Hlth Syst & Univ, Hlth Safety & Environm, Sonora, CA USA. [Drewry, Pamela] Med City Hosp, Employee Hlth, Dallas, TX USA. [Murray, Kathy] Sonora Reg Med Ctr, Risk Management Occupat Hlth, Sonora, CA USA. [DeWitt, Marcie] Baptist Hlth Louisville, Employee Hlth, Louisville, KY USA. [Matsubara, Janet; O'Dea, Louis; Wrighton-Smith, Peter] Oxford lmmunotec, Marlborough, MA USA. [Balser, John] Veristat LLC, Holliston, MA USA. RP King, TC (reprint author), St Vincent Hosp, Dept Pathol & Lab Med, 123 Summer St, Worcester, MA 01608 USA. EM thomas.king@stvincenthospital.com FU Oxford Immunotec, Inc., Marlborough, Massachusetts FX Supported by Oxford Immunotec, Inc., Marlborough, Massachusetts. NR 23 TC 9 Z9 9 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD AUG 1 PY 2015 VL 192 IS 3 BP 367 EP 373 DI 10.1164/rccm.201501-0199OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CO5CZ UT WOS:000359178500018 PM 26017193 ER PT J AU Falkard, B Uddin, T Rahman, MA Franke, MF Aktar, A Uddin, ML Bhuiyan, TR Leung, DT Charles, RIC Larocque, RC Harris, JB Calderwood, SB Qadri, F Ryan, ET AF Falkard, Brie Uddin, Taher Rahman, M. Arifur Franke, Molly F. Aktar, Amena Uddin, Muhammad Lkhtear Bhuiyan, Taufiqur Rahman Leung, Daniel T. Charles, Riche Ile C. Larocque, Regina C. Harris, Jason B. Calderwood, Stephen B. Qadri, Firdausi Ryan, Edward T. TI Plasma Leptin Levels in Children Hospitalized with Cholera in Bangladesh SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID ENVIRONMENTAL ENTERIC DYSFUNCTION; CELL RESPONSES; SIGNALING PATHWAYS; IMMUNE-RESPONSE; O1; VACCINATION; INFECTION; INFANTS; MICE AB Vibrio cholerae, the cause of cholera, induces both innate and adaptive immune responses in infected humans. Leptin is a hormone that plays a role in both metabolism and mediating immune responses. We characterized leptin levels in Ill children with cholera in Bangladesh, assessing leptin levels on days 2, 7, 30, and 180 following cholera. We found that patients at the acute stage of cholera had significantly lower plasma leptin levels than matched controls, and compared with levels in late convalescence. We then assessed immune responses to V cholerae antigens in 74 children with cholera, correlating these responses to plasma leptin levels on day 2 of illness. In multivariate analysis, we found an association between day 2 leptin levels and development of later anti-cholera toxin B subunit (CtxB) responses. This finding appeared to be limited to children with better nutritional status. Interestingly, we found no association between leptin levels and antibody responses to V cholerae lipopolysaccharide, a T cell independent antigen. Our results suggest that leptin levels may be associated with cholera, including the development of immune responses to T cell dependent antigens. C1 [Falkard, Brie; Leung, Daniel T.; Charles, Riche Ile C.; Larocque, Regina C.; Harris, Jason B.; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Int Ctr Diarrhoeal Dis Bangladesh Icddr B, Ctr Vaccine Sci, Dhaka, Bangladesh. Partners Hlth, Boston, MA USA. [Franke, Molly F.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Leung, Daniel T.; Charles, Riche Ile C.; Larocque, Regina C.; Calderwood, Stephen B.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Leung, Daniel T.] Univ Utah, Sch Med, Div Infect Dis, Salt Lake City, UT USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Falkard, B (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Jackson 520,55 Fruit St, Boston, MA 02114 USA. EM bfalkard@partners.org; taher134@yahoo.com; marifur@icddrb.org; molly_franke@hms.harvard.edu; amena.aktar@icddrb.org; muhammaduddin96@yahoo.com; taufiqur@icddrb.org; daniel.leung@utah.edu; rccharlcs@partners.org; rclarocque@partners.org; jbharris@partners.org; scalderwood@partners.org; fqadri@icddrb.org; etryan@partners.org OI leung, daniel/0000-0001-8401-0801 FU National Institutes of Health; National Institute of Allergy and Infectious Diseases [U01 AI058935, U01 AI077883, K08 AI100923, UO1 AI106878, K08 AI089721]; Fogarty International Center, Training Grant in Vaccine Development and Public Health [TW005572]; American Recovery and Reinvestment Act (ARRA) Postdoctoral Fellowship in Global Infectious Diseases, Career Development Awards [K01 TW07409, TW07144]; Fulbright-Fogarty International Clinical Research Scholars Award [R24 TW007988]; Swedish International Development Cooperation Agency; Howard Hughes Medical Institute; American Society for Tropical Medicine; Hygiene-Burroughs Wellcome Fund; Thrasher Research Fund Early Career Award FX This research was supported by core grants to the International Centre for Diarrhoeal Disease Bangladesh and through programs funded by the National Institutes of Health, including the National Institute of Allergy and Infectious Diseases (U01 AI058935 [S.B.C., F.Q., and E.T.R.], U01 AI077883 [E.T.R.], K08 AI100923 [D.T.L.], UO1 AI106878 [E.T.R.], and K08 AI089721 [R.C.C.]), the Fogarty International Center, Training Grant in Vaccine Development and Public Health (TW005572 [T.U. M.I.U., T.R.B., and F.Q.]), and American Recovery and Reinvestment Act (ARRA) Postdoctoral Fellowship in Global Infectious Diseases, Career Development Awards (K01 TW07409 [J.B.H.] and TW07144), and Fulbright-Fogarty International Clinical Research Scholars Award (R24 TW007988 [B.F. and T.U.]), as well as by the Swedish International Development Cooperation Agency (F.Q.), a Physician Scientist Early Career Award from the Howard Hughes Medical Institute (R.C.L.), a Postdoctoral Fellowship in Tropical Infectious Diseases from the American Society for Tropical Medicine and Hygiene-Burroughs Wellcome Fund (D.T.L.), and a Thrasher Research Fund Early Career Award (D.T.L). NR 26 TC 1 Z9 1 U1 2 U2 4 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 EI 1476-1645 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD AUG PY 2015 VL 93 IS 2 BP 244 EP 249 DI 10.4269/ajtmh.15-0172 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA CO7GK UT WOS:000359327400011 PM 26055740 ER PT J AU Coates, AS Winer, EP Goldhirsch, A Gelber, RD Gnant, M Piccart-Gebhart, M Thurlimann, B Senn, HJ AF Coates, A. S. Winer, E. P. Goldhirsch, A. Gelber, R. D. Gnant, M. Piccart-Gebhart, M. Thuerlimann, B. Senn, H. -J. TI Tailoring therapies-improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015 SO ANNALS OF ONCOLOGY LA English DT Article DE surgery; radiation therapy; systemic adjuvant therapies; early breast cancer; St Gallen Consensus ID PATHOLOGICAL COMPLETE RESPONSE; TUMOR-INFILTRATING LYMPHOCYTES; CONTRALATERAL PROPHYLACTIC MASTECTOMY; OVARIAN-FUNCTION SUPPRESSION; HERCEPTIN ADJUVANT TRIAL; BRCA2 MUTATION CARRIERS; LATE-DISTANT RECURRENCE; NEOADJUVANT CHEMOTHERAPY; ESTROGEN-RECEPTOR; ENDOCRINE THERAPY AB The 14th St Gallen International Breast Cancer Conference (2015) reviewed substantial new evidence on locoregional and systemic therapies for early breast cancer. Further experience has supported the adequacy of tumor margins defined as 'no ink on invasive tumor or DCIS' and the safety of omitting axillary dissection in specific cohorts. Radiotherapy trials support irradiation of regional nodes in node-positive disease. Considering subdivisions within luminal disease, the Panel was more concerned with indications for the use of specific therapies, rather than surrogate identification of intrinsic subtypes as measured by multiparameter molecular tests. For the treatment of HER2-positive disease in patients with node-negative cancers up to 1 cm, the Panel endorsed a simplified regimen comprising paclitaxel and trastuzumab without anthracycline as adjuvant therapy. For premenopausal patients with endocrine responsive disease, the Panel endorsed the role of ovarian function suppression with either tamoxifen or exemestane for patients at higher risk. The Panel noted the value of an LHRH agonist given during chemotherapy for premenopausal women with ER-negative disease in protecting against premature ovarian failure and preserving fertility. The Panel noted increasing evidence for the prognostic value of commonly used multiparameter molecular markers, some of which also carried prognostic information for late relapse. The Panel noted that the results of such tests, where available, were frequently used to assist decisions about the inclusion of cytotoxic chemotherapy in the treatment of patients with luminal disease, but noted that threshold values had not been established for this purpose for any of these tests. Multiparameter molecular assays are expensive and therefore unavailable in much of the world. The majority of new breast cancer cases and breast cancer deaths now occur in less developed regions of the world. In these areas, less expensive pathology tests may provide valuable information. The Panel recommendations on treatment are not intended to apply to all patients, but rather to establish norms appropriate for the majority. Again, economic considerations may require that less expensive and only marginally less effective therapies may be necessary in less resourced areas. Panel recommendations do not imply unanimous agreement among Panel members. Indeed, very few of the 200 questions received 100% agreement from the Panel. In the text below, wording is intended to convey the strength of Panel support for each recommendation, while details of Panel voting on each question are available in supplementary Appendix S2, available at Annals of Oncology online. C1 [Coates, A. S.] Univ Sydney, Int Breast Canc Study Grp, Sydney, NSW 2006, Australia. [Winer, E. P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Goldhirsch, A.] European Inst Oncol, Program Breast Hlth Senol, Int Breast Canc Study Grp, I-20141 Milan, Italy. [Gelber, R. D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Stat Ctr,Dept Biostat & Computat Biol,Int Breast, Boston, MA 02115 USA. [Gnant, M.] Med Univ Vienna, Dept Surg, Vienna, Austria. [Gnant, M.] Med Univ Vienna, Ctr Comprehens Canc, Vienna, Austria. [Piccart-Gebhart, M.] Inst Jules Bordet, Internal Med Oncol, B-1000 Brussels, Belgium. [Thuerlimann, B.] Kantonsspital, Breast Ctr, St Gallen, Switzerland. [Senn, H. -J.] Tumor & Breast Ctr ZeTuP, St Gallen, Switzerland. RP Goldhirsch, A (reprint author), European Inst Oncol, Program Breast Hlth Senol, Via Ripamonti 435, I-20141 Milan, Italy. EM aron.goldhirsch@ibcsg.org RI Goodwin, Pamela/K-1477-2013; OI Cardoso, Fatima/0000-0002-6692-2249 FU United States National Cancer Institute (IBCSG Statistical Center) [CA75362]; Susan G. Komen(R) [SPP150019] FX Support for the conference was provided by the Educative Foundation, St Gallen Oncology Conferences (SONK) from registration fees paid by the conference attendees; by Grant No. CA75362 from the United States National Cancer Institute (IBCSG Statistical Center, M. Regan, PI) and by Susan G. Komen (R) (grant No SPP150019). NR 116 TC 215 Z9 237 U1 9 U2 44 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 2015 VL 26 IS 8 BP 1533 EP 1546 DI 10.1093/annonc/mdv221 PG 14 WC Oncology SC Oncology GA CO7BI UT WOS:000359312100008 PM 25939896 ER PT J AU Gillessen, S Omlin, A Attard, G de Bono, JS Efstathiou, E Fizazi, K Halabi, S Nelson, PS Sartor, O Smith, MR Soule, HR Akaza, H Beer, TM Beltran, H Chinnaiyan, AM Daugaard, G Davis, ID De Santis, M Drake, CG Eeles, RA Fanti, S Gleave, ME Heidenreich, A Hussain, M James, ND Lecouvet, FE Logothetis, CJ Mastris, K Nilsson, S Oh, WK Olmos, D Padhani, AR Parker, C Rubin, MA Schalken, JA Scher, HI Sella, A Shore, ND Small, EJ Sternberg, CN Suzuki, H Sweeney, CJ Tannock, IF Tombal, B AF Gillessen, S. Omlin, A. Attard, G. de Bono, J. S. Efstathiou, E. Fizazi, K. Halabi, S. Nelson, P. S. Sartor, O. Smith, M. R. Soule, H. R. Akaza, H. Beer, T. M. Beltran, H. Chinnaiyan, A. M. Daugaard, G. Davis, I. D. De Santis, M. Drake, C. G. Eeles, R. A. Fanti, S. Gleave, M. E. Heidenreich, A. Hussain, M. James, N. D. Lecouvet, F. E. Logothetis, C. J. Mastris, K. Nilsson, S. Oh, W. K. Olmos, D. Padhani, A. R. Parker, C. Rubin, M. A. Schalken, J. A. Scher, H. I. Sella, A. Shore, N. D. Small, E. J. Sternberg, C. N. Suzuki, H. Sweeney, C. J. Tannock, I. F. Tombal, B. TI Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015 SO ANNALS OF ONCOLOGY LA English DT Article DE advanced prostate cancer; castration-resistant prostate cancer; therapeutics; consensus; castration-naive prostate cancer ID METASTASIS-FREE SURVIVAL; INTERMITTENT ANDROGEN SUPPRESSION; PLACEBO-CONTROLLED TRIAL; SPINAL-CORD COMPRESSION; III EXTENSION TRIAL; ABIRATERONE ACETATE; BONE METASTASES; PHASE-III; RANDOMIZED-TRIAL; ZOLEDRONIC ACID AB The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naive prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary Material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with APC in clinical trials should be encouraged. C1 [Gillessen, S.; Omlin, A.] Kantonsspital St Gallen, Dept Oncol Haematol, St Gallen, Switzerland. [Attard, G.; de Bono, J. S.] Royal Marsden NHS Fdn Trust, Prostate Canc Targeted Therapy Grp, Sutton, Surrey, England. [Attard, G.; de Bono, J. S.] Royal Marsden NHS Fdn Trust, Drug Dev Unit, Sutton, Surrey, England. [Attard, G.; de Bono, J. S.] Inst Canc Res, Sutton, Surrey, England. [Efstathiou, E.; Logothetis, C. J.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA. [Efstathiou, E.; Logothetis, C. J.] Univ Texas MD Anderson Canc Ctr, David H Koch Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA. [Efstathiou, E.] Univ Athens, Alexandra Hosp, Dept Clin Therapeut, Sch Med, Athens 11528, Greece. [Fizazi, K.] Univ Paris 11, Inst Gustave Roussy, Dept Canc Med, Villejuif, France. [Halabi, S.] Duke Univ, Dept Biostat & Bioinformat, Durham, NC 27706 USA. [Nelson, P. S.] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98104 USA. [Sartor, O.] Tulane Univ, Tulane Canc Ctr, New Orleans, LA 70118 USA. [Smith, M. R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Soule, H. R.] Prostate Canc Fdn, Santa Monica, CA USA. [Akaza, H.] Univ Tokyo, Adv Sci & Technol Res Ctr, Tokyo, Japan. [Beer, T. M.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Beltran, H.; Scher, H. I.] Weill Cornell Med Coll, Dept Med, New York, NY USA. [Chinnaiyan, A. M.] Univ Michigan, Sch Med, Dept Pathol, Michigan Ctr Translat Pathol, Ann Arbor, MI USA. [Chinnaiyan, A. M.] Univ Michigan, Sch Med, Ctr Comprehens Canc, Dept Urol, Ann Arbor, MI USA. [Chinnaiyan, A. M.] Univ Michigan, Sch Med, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA. [Daugaard, G.] Copenhagen Univ Hosp, Rigshosp, Dept Oncol, Copenhagen, Denmark. [Davis, I. D.] Monash Univ & Eastern Hlth, Eastern Hlth Clin Sch, Box Hill, Vic, Australia. [De Santis, M.] Univ Warwick, Canc Res Ctr, Warwick, England. [De Santis, M.] Kaiser Franz Josef Spital, Ludwig Boltzmann Inst Appl Canc Res, Vienna, Austria. [Drake, C. G.] Johns Hopkins Univ, Sch Med, Johns Hopkins Sidney Kimmel Canc Ctr, Baltimore, MD USA. [Drake, C. G.] Johns Hopkins Univ, Sch Med, Brady Urol Inst, Dept Urol, Baltimore, MD USA. [Eeles, R. A.] Inst Canc Res, London SW3 6JB, England. [Eeles, R. A.] Royal Marsden NHS Fdn Trust, London, England. [Fanti, S.] Univ Bologna, Policlin S Orsola, Dept Nucl Med, Bologna, Italy. [Gleave, M. E.] Univ British Columbia, Vancouver Prostate Ctr, Urol Sci, Vancouver, BC V5Z 1M9, Canada. [Heidenreich, A.] Rhein Westfal TH Aachen, Klinik & Poliklin Urol, Aachen, Germany. [Hussain, M.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [James, N. D.] Univ Hosp Birmingham, Queen Elizabeth Hosp Birmingham, Birmingham, W Midlands, England. [Lecouvet, F. E.] Clin Univ St Luc, Ctr Canc, Dept Radiol, B-1200 Brussels, Belgium. [Lecouvet, F. E.] Clin Univ St Luc, Inst Rech Expt & Clin, B-1200 Brussels, Belgium. [Mastris, K.] Europa Uomo Prostate Patients, Clayhall Ilford, Essex, England. [Nilsson, S.] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden. [Oh, W. K.] Icahn Sch Med Mt Sinai, Tisch Canc Inst, Div Haematol & Med Oncol, New York, NY 10029 USA. [Olmos, D.] Spanish Natl Canc Res Ctr CNIO, Prostate Canc Clin Res Unit, Madrid, Spain. [Olmos, D.] Hosp Univ Virgen Victoria & Reg Malaga, CNIO IBIMA Genitourinary Canc Unit, Malaga, Spain. [Olmos, D.] Ctr Integral Onco Clara Campal CIOCC, Madrid, Spain. [Padhani, A. R.] Mt Vernon Canc Ctr, Paul Strickland Scanner Ctr, Northwood, Middx, England. [Parker, C.] Royal Marsden NHS Fdn Trust, Acad Urol Unit, Prostate Canc Targeted Therapy Grp, Sutton, Surrey, England. [Parker, C.] Royal Marsden NHS Fdn Trust, Dept Diagnost Radiol, Sutton, Surrey, England. [Parker, C.] Inst Canc Res, Sutton, Surrey, England. [Rubin, M. A.] Weill Cornell Med Coll & NewYork Presbyterian, Dept Pathol & Urol, Meyer Canc Ctr, Inst Precis Med, New York, NY USA. [Schalken, J. A.] Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6525 ED Nijmegen, Netherlands. [Scher, H. I.] Mem Sloan Kettering Canc Ctr, Dept Med, Genitourinary Oncol Serv, New York, NY 10021 USA. [Sella, A.] Tel Aviv Univ, Sackler Sch Med, Assaf Harofeh Med Ctr, Dept Oncol, Zerifin, Israel. [Shore, N. D.] Carolina Urol Res Ctr, Dept Urol, Myrtle Beach, SC USA. [Small, E. J.] UCSF, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Sternberg, C. N.] San Camillo & Forlanini Hosp, Dept Med Oncol, Rome, Italy. [Suzuki, H.] Toho Univ, Sakura Med Ctr, Dept Urol, Chiba 2748510, Japan. [Sweeney, C. J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sweeney, C. J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. [Tannock, I. F.] Princess Margaret Canc Ctr, Dept Med Oncol & Haematol, Toronto, ON, Canada. [Tombal, B.] Catholic Univ Louvain, Inst Rech Clin, Serv Urol, B-1200 Brussels, Belgium. RP Gillessen, S (reprint author), Kantonsspital St Gallen, Dept Oncol Haematol, Rorschacherstr 95, St Gallen, Switzerland. EM silke.gillessen@kssg.ch RI Schalken, Jack/B-1277-2014; OI Schalken, Jack/0000-0001-8274-7797; Daugaard, Gedske/0000-0002-9618-9180; Eeles, Rosalind/0000-0002-3698-6241; Rubin, Mark/0000-0002-8321-9950; Attard, Gerhardt/0000-0002-4811-7983 FU Cantonal Hospital St Gallen; City and Canton of St Gallen; Swiss Cancer Research Organisation; European School of Oncology (ESO); Swiss Cancer League; Swiss Oncology Research Network SAKK; Swiss Cancer Foundation; Prostate Cancer Foundation (PCF); Gunter and Regine Kelm Foundation; Movember Foundation FX We gratefully acknowledge the financial support of the following non-profit organisations for the Advanced Prostate Cancer Consensus Conference (APCCC): Cantonal Hospital St Gallen, City and Canton of St Gallen, Swiss Cancer Research Organisation, European School of Oncology (ESO), Swiss Cancer League, the Swiss Oncology Research Network SAKK, Swiss Cancer Foundation, Prostate Cancer Foundation (PCF) and the Gunter and Regine Kelm Foundation. We thank the Movember Foundation for the sponsoring of the travel grants (no grant number). NR 88 TC 52 Z9 53 U1 3 U2 16 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 2015 VL 26 IS 8 BP 1589 EP 1604 DI 10.1093/annonc/mdv257 PG 16 WC Oncology SC Oncology GA CO7BI UT WOS:000359312100011 PM 26041764 ER PT J AU Ramalingam, S Goss, G Rosell, R Schmid-Bindert, G Zaric, B Andric, Z Bondarenko, I Komov, D Ceric, T Khuri, F Samarzija, M Felip, E Ciuleanu, T Hirsh, V Wehler, T Spicer, J Salgia, R Shapiro, G Sheldon, E Teofilovici, F Vukovic, V Fennell, D AF Ramalingam, S. Goss, G. Rosell, R. Schmid-Bindert, G. Zaric, B. Andric, Z. Bondarenko, I. Komov, D. Ceric, T. Khuri, F. Samarzija, M. Felip, E. Ciuleanu, T. Hirsh, V. Wehler, T. Spicer, J. Salgia, R. Shapiro, G. Sheldon, E. Teofilovici, F. Vukovic, V. Fennell, D. TI A randomized phase II study of ganetespib, a heat shock protein 90 inhibitor, in combination with docetaxel in second-line therapy of advanced non-small cell lung cancer (GALAXY-1) SO ANNALS OF ONCOLOGY LA English DT Article DE ganetespib; docetaxel; advanced NSCLC; adenocarcinoma; HSP90 inhibitor ID BREAST-CANCER; HIF-1-ALPHA; HYPOXIA; RESISTANCE; MODELS; LDH-5 AB Background: This trial was designed to evaluate the activity and safety of ganetespib in combination with docetaxel in advanced non-small cell lung cancer (NSCLC) and to identify patient populations most likely to benefit from the combination. Patients and methods: Patients with one prior systemic therapy for advanced disease were eligible. Docetaxel (75 mg/m(2) on day 1) was administered alone or with ganetespib (150 mg/m(2) on days 1 and 15) every 3 weeks. The primary end points were progression-free survival (PFS) in two subgroups of the adenocarcinoma population: patients with elevated lactate dehydrogenase (eLDH) and mutated KRAS (mKRAS). Results: Of 385 patients enrolled, 381 were treated. Early in the trial, increased hemoptysis and lack of efficacy were observed in nonadenocarcinoma patients (n = 71); therefore, only patients with adenocarcinoma histology were subsequently enrolled. Neutropenia was the most common grade >= 3 adverse event: 41% in the combination arm versus 42% in docetaxel alone. There was no improvement in PFS for the combination arm in the eLDH (N = 114, adjusted hazard ratio (HR) = 0.77, P = 0.1134) or mKRAS (N = 89, adjusted HR = 1.11, P = 0.3384) subgroups. In the intent-to-treat adenocarcinoma population, there was a trend in favor of the combination, with PFS (N = 253, adjusted HR = 0.82, P = 0.0784) and overall survival (OS) (adjusted HR = 0.84, P = 0.1139). Exploratory analyses showed significant benefit of the ganetespib combination in the prespecified subgroup of adenocarcinoma patients diagnosed with advanced disease > 6 months before study entry (N = 177): PFS (adjusted HR = 0.74, P = 0.0417); OS (adjusted HR = 0.69, P = 0.0191). Conclusion: Advanced lung adenocarcinoma patients treated with ganetespib in combination with docetaxel had an acceptable safety profile. While the study's primary end points were not met, significant prolongation of PFS and OS was observed in patients > 6 months from diagnosis of advanced disease, a subgroup chosen as the target population for the phase III study. C1 [Ramalingam, S.; Khuri, F.] Emory Univ, Sch Med, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA. [Goss, G.] Univ Ottawa, Div Med Oncol, Ottawa, ON, Canada. [Rosell, R.] Catalan Inst Oncol, Med Oncol Serv, Badalona, Spain. [Schmid-Bindert, G.] Univ Med Ctr Mannheim, Dept Surg, Mannheim, Germany. [Zaric, B.] Univ Novi Sad, Fac Med, Inst Pulm Dis Vojvodina, YU-21000 Novi Sad, Serbia. [Andric, Z.] Med Ctr Bezanijska Kosa, Clin Oncol, Belgrade, Serbia. [Bondarenko, I.] Multiple Discipline Clin Hosp 4, Dept Oncol, Dnepropetrovsk, Ukraine. [Komov, D.] Russian Acad Med Sci, Surg Dept Tumor Diagnost, Moscow, Russia. [Ceric, T.] Univ Sarajevo, Ctr Clin, Clin Oncol, Sarajevo 71000, Bosnia & Herceg. [Samarzija, M.] Univ Zagreb, Dept Resp Dis Jordanovac, Zagreb 41000, Croatia. [Felip, E.] Vall dHebron Univ Hosp, Dept Med Oncol, Barcelona, Spain. [Ciuleanu, T.] Oncol Inst Ion Chiricuta, Dept Med Oncol, Cluj Napoca, Romania. [Hirsh, V.] McGill Univ, Ctr Hlth, Dept Med Oncol, Montreal, PQ, Canada. [Wehler, T.] Johannes Gutenberg Univ Mainz, Dept Internal Med 3, D-55122 Mainz, Germany. [Spicer, J.] Kings Coll London, Dept Res Oncol, London, England. [Salgia, R.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Shapiro, G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sheldon, E.; Teofilovici, F.; Vukovic, V.] Synta Pharmaceut Corp, Dept Clin Res, Lexington, MA USA. [Fennell, D.] Univ Leicester, Dept Canc Studies, Leicester, Leics, England. RP Ramalingam, S (reprint author), Emory Univ, Sch Med, Winship Canc Inst, Dept Hematol & Med Oncol, 1365-C Clifton Rd NE, Atlanta, GA 30322 USA. EM ssramal@emory.edu OI Bondarenko, Igor/0000-0002-7071-2471 FU Synta Pharmaceuticals Corporation FX The work was supported by Synta Pharmaceuticals Corporation (no grant number). NR 14 TC 14 Z9 16 U1 2 U2 9 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 2015 VL 26 IS 8 BP 1741 EP 1748 DI 10.1093/annonc/mdv220 PG 8 WC Oncology SC Oncology GA CO7BI UT WOS:000359312100029 PM 25997818 ER PT J AU Gakis, G Morgan, TM Daneshmand, S Keegan, KA Todenhofer, T Mischinger, J Schubert, T Zaid, HB Hrbacek, J Ali-El-Dein, B Clayman, RH Galland, S Olugbade, K Rink, M Fritsche, HM Burger, M Chang, SS Babjuk, M Thalmann, GN Stenzl, A Efstathiou, JA AF Gakis, G. Morgan, T. M. Daneshmand, S. Keegan, K. A. Todenhoefer, T. Mischinger, J. Schubert, T. Zaid, H. B. Hrbacek, J. Ali-El-Dein, B. Clayman, R. H. Galland, S. Olugbade, K. Rink, M. Fritsche, H. -M. Burger, M. Chang, S. S. Babjuk, M. Thalmann, G. N. Stenzl, A. Efstathiou, J. A. TI Impact of perioperative chemotherapy on survival in patients with advanced primary urethral cancer: results of the international collaboration on primary urethral carcinoma SO ANNALS OF ONCOLOGY LA English DT Article DE primary urethral carcinoma; adjuvant; neoadjuvant; chemotherapy; chemoradiotherapy ID UROTHELIAL CARCINOMA; BLADDER; TRACT AB Background: To investigate the impact of perioperative chemo(radio) therapy in advanced primary urethral carcinoma (PUC). Patients and methods: A series of 124 patients (86 men, 38 women) were diagnosed with and underwent surgery for PUC in 10 referral centers between 1993 and 2012. Kaplan-Meier analysis with log-rank testing was used to investigate the impact of perioperative chemo(radio) therapy on overall survival (OS). The median follow-up was 21 months (mean: 32 months; interquartile range: 5-48). Results: Neoadjuvant chemotherapy (NAC), neoadjuvant chemoradiotherapy (N-CRT) plus adjuvant chemotherapy (ACH), and ACH was delivered in 12 (31%), 6 (15%) and 21 (54%) of these patients, respectively. Receipt of NAC/N-CRT was associated with clinically node-positive disease (cN+; P = 0.033) and lower utilization of cystectomy at surgery (P = 0.015). The objective response rate to NAC and N-CRT was 25% and 33%, respectively. The 3-year OS for patients with objective response to neoadjuvant treatment (complete/partial response) was 100% and 58.3% for those with stable or progressive disease (P = 0.30). Of the 26 patients staged >= cT3 and/or cN+ disease, 16 (62%) received perioperative chemo(radio) therapy and 10 upfront surgery without perioperative chemotherapy (38%). The 3-year OS for this locally advanced subset of patients (>= cT3 and/or cN+) who received NAC (N = 5), N-CRT (N = 3), surgery-only (N = 10) and surgery plus ACH (N = 8) was 100%, 100%, 50% and 20%, respectively (P = 0.016). Among these 26 patients, receipt of neoadjuvant treatment was significantly associated with improved 3-year relapse-free survival (RFS) (P = 0.022) and OS (P = 0.022). Proximal tumor location correlated with inferior 3-year RFS and OS (P = 0.056/0.005). Conclusion: In this series, patients who received NAC/N-CRT for cT3 and/or cN+ PUC appeared to demonstrate improved survival compared with those who underwent upfront surgery with or without ACH. C1 [Gakis, G.; Todenhoefer, T.; Mischinger, J.; Schubert, T.; Stenzl, A.] Univ Tubingen, Dept Urol, D-72076 Tubingen, Germany. [Morgan, T. M.; Olugbade, K.] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. [Daneshmand, S.] USC Norris Comprehens Canc Ctr, Inst Urol, Los Angeles, CA USA. [Keegan, K. A.; Zaid, H. B.; Chang, S. S.] Vanderbilt Univ, Med Ctr, Dept Urol Surg, Nashville, TN USA. [Hrbacek, J.; Babjuk, M.] Charles Univ Prague, Dept Urol, Sch Med 2, Prague, Czech Republic. [Ali-El-Dein, B.] Mansoura Clin, Urol & Nephrol Ctr, Mansoura, Egypt. [Clayman, R. H.; Galland, S.; Efstathiou, J. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiooncol, Boston, MA USA. [Rink, M.] Univ Med Ctr Hamburg Eppendorf, Dept Urol, Hamburg, Germany. [Fritsche, H. -M.; Burger, M.] Univ Hosp Regensburg, Dept Urol, Regensburg, Germany. [Thalmann, G. N.] Univ Hosp Bern, Dept Urol, CH-3010 Bern, Switzerland. RP Gakis, G (reprint author), Univ Tubingen, Univ Tubingen Hosp, Dept Urol, Hoppe Seyler Str 3, D-72076 Tubingen, Germany. EM georgios.gakis@googlemail.com NR 13 TC 4 Z9 4 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 2015 VL 26 IS 8 BP 1754 EP 1759 DI 10.1093/annonc/mdv230 PG 6 WC Oncology SC Oncology GA CO7BI UT WOS:000359312100031 PM 25969370 ER PT J AU Shue, B Damle, RN Flahive, J Kalish, JA Stone, DH Patel, VI Schanzer, A Baril, DT AF Shue, Bing Damle, Rachelle N. Flahive, Julie Kalish, Jeffrey A. Stone, David H. Patel, Virendra I. Schanzer, Andres Baril, Donald T. TI The Increased Use of Computed Tomography Angiography and Magnetic Resonance Angiography as the Sole Imaging Modalities Prior to Infrainguinal Bypass Has Had No Effect on Outcomes SO ANNALS OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT Meeting of the Society-for-Clinical-Vascular-Surgery CY MAR 17, 2014 CL Carlsbad, CA SP Soc Clin Vasc Surg ID PERIPHERAL ARTERIAL-DISEASE; CRITICAL LIMB ISCHEMIA; METAANALYSIS; PREVALENCE; SURGERY AB Background: Angiography remains the gold standard imaging modality before infrainguinal bypass. Computed tomography angiography (CTA) and magnetic resonance angiography (MRA) have emerged as noninvasive alternatives for preoperative imaging. We sought to examine contemporary trends in the utilization of CTA and MRA as isolated imaging modalities before infrainguinal bypass and to compare outcomes following infrainguinal bypass in patients who underwent CTA or MRA versus those who underwent conventional arteriography. Methods: Patients undergoing infrainguinal bypass within the Vascular Study Group of New England were identified (2003-2012). Patients were stratified by preoperative imaging modality: CTA/MRA alone or conventional angiography. Trends in utilization of these modalities were examined and demographics of these groups were compared. Primary end points included primary patency, secondary patency, and major adverse limb events (MALE) at 1 year as determined by Kaplan-Meier analysis. Multivariable Cox proportional hazards models were constructed to evaluate the effect of imaging modality on primary patency, secondary patency, and MALE after adjusting for confounders. Results: In 3123 infrainguinal bypasses, CTA/MRA alone was used in 462 cases (15%) and angiography was used in 2661 cases (85%). Use of CTA/MRA alone increased over time, with 52 (11%) bypasses performed between 2003 and 2005, 189 (41%) bypasses performed between 2006 and 2009, and 221 (48%) bypasses performed between 2010 and 2012 (P < 0.001). Patients with CTA/MRA alone, compared with patients with angiography, more frequently underwent bypass for claudication (33% vs. 26%, P = 0.001) or acute limb ischemia (13% vs. 5%, P < 0.0001), more frequently had prosthetic conduits (39% vs. 30%, P = 0.001), and less frequently had tibial/pedal targets (32% vs. 40%, P = 0.002). After adjusting for these and other confounders, multivariable analysis demonstrated that the use of CTA/MRA alone was not associated with a significant difference in 1 year primary patency (hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.78-1.16), secondary patency (HR 1.30, 95% CI 0.99-1.72), or MALE (HR 1.08, 95% CI 0.89-1.32). Conclusions: CTA and MRA are being increasingly used as the sole preoperative imaging modality before infrainguinal bypass. This shift in practice patterns appears to have no measurable effect on outcomes at 1 year. C1 [Shue, Bing; Schanzer, Andres] Univ Massachusetts, Med Ctr, Div Vasc & Endovasc Surg, Worcester, MA 01545 USA. [Damle, Rachelle N.; Flahive, Julie] Univ Massachusetts, Med Ctr, Dept Surg, Worcester, MA 01545 USA. [Kalish, Jeffrey A.] Boston Univ, Med Ctr, Div Vasc & Endovasc Surg, Boston, MA USA. [Stone, David H.] Dartmouth Hitchcock Med Ctr, Div Vasc Surg, Lebanon, NH 03766 USA. [Patel, Virendra I.] Massachusetts Gen Hosp, Div Vasc Surg, Boston, MA 02114 USA. [Baril, Donald T.] Univ Pittsburgh, Med Ctr, Div Vasc Surg, Pittsburgh, PA USA. RP Shue, B (reprint author), Univ Massachusetts, Med Ctr, Div Vasc Surg, 55 Lake Ave North, Worcester, MA 01545 USA. EM bing.shue@umassmemorial.org NR 22 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0890-5096 EI 1615-5947 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD AUG PY 2015 VL 29 IS 6 BP 1245 EP 1254 DI 10.1016/j.avsg.2015.03.039 PG 10 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA CO7BH UT WOS:000359312000025 PM 26032010 ER PT J AU Ryan, CJ de Bono, JS Smith, MR Rathkopf, DE Mulders, PFA Small, EJ Shore, ND Fizazi, K De Porre, P Kheoh, T Li, JH Todd, MB Griffin, TW Saad, F AF Ryan, Charles J. de Bono, Johann S. Smith, Matthew R. Rathkopf, Dana E. Mulders, Peter F. A. Small, Eric J. Shore, Neal D. Fizazi, Karim De Porre, Peter Kheoh, Thian Li, Jinhui Todd, Mary B. Griffin, Thomas W. Saad, Fred TI Antitumor activity of taxane chemotherapy as first subsequent therapy after abiraterone acetate (AA) in study COU-AA-302 for metastatic castration-resistant prostate cancer (mCRPC) SO BJU INTERNATIONAL LA English DT Meeting Abstract CT 2nd Prostate Cancer World Congress (PCWC) CY AUG 17-21, 2015 CL Cairns, AUSTRALIA SP Australian Prostate Canc Res C1 [Ryan, Charles J.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [de Bono, Johann S.] Royal Marsden Hosp, London, England. [Smith, Matthew R.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Smith, Matthew R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rathkopf, Dana E.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Rathkopf, Dana E.] Weill Cornell Med Coll, New York, NY USA. [Mulders, Peter F. A.] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Small, Eric J.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Shore, Neal D.] Atlantic Urol Clin, Carolina Urol Res Ctr, Myrtle Beach, SC USA. [Fizazi, Karim] Univ Paris 11, Inst Gustave Roussy, Paris, France. [De Porre, Peter; Kheoh, Thian; Griffin, Thomas W.] Janssen Res & Dev, Raritan, NJ USA. [Li, Jinhui] Johnson & Johnson Med China, Shanghai, Peoples R China. [Saad, Fred] Univ Montreal, Montreal, PQ H3C 3J7, Canada. RI Mulders, Peter/H-8076-2014 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD AUG PY 2015 VL 116 SU 1 SI SI MA 088 BP 12 EP 12 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA CO6GC UT WOS:000359254200033 ER PT J AU Bolte, S Ciaramidaro, A Schlitt, S Hainz, D Kliemann, D Beyer, A Poustka, F Freitag, C Walter, H AF Bolte, Sven Ciaramidaro, Angela Schlitt, Sabine Hainz, Daniela Kliemann, Dorit Beyer, Anke Poustka, Fritz Freitag, Christine Walter, Henrik TI Training-induced plasticity of the social brain in autism spectrum disorder SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID FACIAL EMOTION RECOGNITION; ASPERGER-SYNDROME; MIND; EXPRESSIONS; PERCEPTION; EXPLICIT; IMPLICIT; SYSTEM AB Background Autism spectrum disorder (ASD) is linked to social brain activity and facial affect recognition (FAR). Aims To examine social brain plasticity in ASD. Method Using FAR tests and functional magnetic resonance imaging tasks for FAR, we compared 32 individuals with ASD and 25 controls. Subsequently, the participants with ASD were assigned to FAR computer-aided cognitive training or a control group. Results The ASD group performed more poorly than controls on explicit behavioural FAR tests. In the scanner, during implicit FAR, the amygdala, fusiform gyrus and other regions of the social brain were less activated bilaterally. The training group improved on behavioural FAR tests, and cerebral response to implicit affect processing tasks increased bilaterally post-training in the social brain. Conclusions Individuals with ASD show FAR impairments associated with hypoactivation of the social brain. Computer-based training improves explicit FAR and neuronal responses during implicit FAR, indicating neuroplasticity in the social brain in ASD. Copyright and usage (C) The Royal College of Psychiatrists, all rights reserved. C1 [Bolte, Sven] Karolinska Inst, Ctr Neurodev Disorders, Dept Womens & Childrens Hlth, S-11330 Stockholm, Sweden. [Bolte, Sven; Ciaramidaro, Angela; Schlitt, Sabine; Hainz, Daniela; Beyer, Anke; Poustka, Fritz; Freitag, Christine] Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat Psychosomat & Ps, Frankfurt, Germany. [Kliemann, Dorit] Free Univ Berlin, Cluster Excellence Languages Emot, Berlin, Germany. [Kliemann, Dorit] Free Univ Berlin, Dept Educ & Psychol, Berlin, Germany. [Kliemann, Dorit] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Kliemann, Dorit] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Walter, Henrik] Charite, Dept Psychiat & Psychotherapy, D-13353 Berlin, Germany. RP Bolte, S (reprint author), Karolinska Inst, CAP Res Ctr, Dept Womens & Childrens Hlth, Ctr Neurodev Disorders,Neuropsychiat Unit, Gavlegatan 22, S-11330 Stockholm, Sweden. EM sven.bolte@ki.se RI Walter, Henrik/O-2612-2013; OI Ciaramidaro, Angela/0000-0003-1157-6702 FU Swedish Research Council [523-2009-7054] FX S.B. was supported by the Swedish Research Council (grant no 523-2009-7054) NR 47 TC 4 Z9 5 U1 8 U2 19 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 EI 1472-1465 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD AUG PY 2015 VL 207 IS 2 BP 149 EP 157 DI 10.1192/bjp.bp.113.143784 PG 9 WC Psychiatry SC Psychiatry GA CO5DW UT WOS:000359180800010 PM 25792694 ER PT J AU Charlton, BM Wu, KN Zhang, XH Giovannucci, EL Fuchs, CS Missmer, SA Rosner, B Hankinson, SE Willett, WC Michels, KB AF Charlton, Brittany M. Wu, Kana Zhang, Xuehong Giovannucci, Edward L. Fuchs, Charles S. Missmer, Stacey A. Rosner, Bernard Hankinson, Susan E. Willett, Walter C. Michels, Karin B. TI Oral Contraceptive Use and Colorectal Cancer in the Nurses' Health Study I and II SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HORMONE REPLACEMENT THERAPY; LARGE-BOWEL-CANCER; BODY-MASS INDEX; COLON-CANCER; REPRODUCTIVE FACTORS; UNITED-STATES; POSTMENOPAUSAL WOMEN; EXOGENOUS HORMONES; CIGARETTE-SMOKING; ROYAL-COLLEGE AB Background: It remains unclear if oral contraceptive (OC) use is associated with the incidence of colorectal cancer. Few studies have examined this association by duration of OC use, time since last OC use, and different cancer subsites. Methods: Among 88,691 participants of the Nurses' Health Study I (NHSI) and 93,080 participants of the Nurses' Health Study II (NHSII), we assessed OC use every 2 years between 1976 and 2010 and categorized it as ever use, duration of use, and time since last use. We included incident colorectal cancer cases through 2010 (NHSI: age at diagnosis = 36-88, N = 1,764; NHSII: age at diagnosis = 33-64, N = 206). Multivariable hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards regression models. Results: Ever OC use was not associated with colorectal cancer in NHSI [1.01 (0.91, 1.12)] nor NHSII [1.03 (0.69, 1.53)]. In NHSII, when compared with never-users, longer durations (5 + years) of OC use were inversely associated with the risk of colon cancers (P-trend = 0.02) but the number of endpoints was limited. No other colorectal cancer subsites were associated with OC durations or times since last OC use in either cohort. Conclusions: In two large prospective cohorts, we found little evidence that OC use may be protective for colorectal cancer, except potentially with longer durations of use among younger women. Impact: Our results do not support the previous initial studies that reported an inverse association of recent OC use with colorectal cancer but instead support newer, larger studies demonstrating no such association. (C)2015 AACR. C1 [Charlton, Brittany M.; Giovannucci, Edward L.; Missmer, Stacey A.; Hankinson, Susan E.; Willett, Walter C.; Michels, Karin B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Charlton, Brittany M.] Boston Childrens Hosp, Div Adolescent & Young Adult Med, Boston, MA USA. [Charlton, Brittany M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Wu, Kana; Giovannucci, Edward L.; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Zhang, Xuehong; Giovannucci, Edward L.; Missmer, Stacey A.; Rosner, Bernard; Hankinson, Susan E.; Willett, Walter C.; Michels, Karin B.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Zhang, Xuehong; Giovannucci, Edward L.; Missmer, Stacey A.; Rosner, Bernard; Hankinson, Susan E.; Willett, Walter C.; Michels, Karin B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Missmer, Stacey A.] Brigham & Womens Hosp, Div Reprod Med, Boston, MA 02115 USA. [Hankinson, Susan E.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, Boston, MA 02125 USA. [Michels, Karin B.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. RP Charlton, BM (reprint author), Harvard Univ, Sch Publ Hlth, 677 Huntington Ave, Boston, MA 02115 USA. EM bcharlton@mail.harvard.edu FU National Institutes of Health [UM1CA176726]; Training Program in Cancer Epidemiology under grant from the National Cancer Institute [T32CA09001]; Training Grant in Reproductive, Perinatal, and Pediatric Epidemiology from the National Institute of Child Health and Human Development, National Institutes of Health [T32HD060454]; [P01CA87969]; [UM1CA186107] FX The NHSI was supported by research grants P01CA87969 and UM1CA186107 and the NHSII was supported by research grant UM1CA176726 of the National Institutes of Health. B.M. Charlton was supported by the Training Program in Cancer Epidemiology under grant T32CA09001 from the National Cancer Institute and the Training Grant T32HD060454 in Reproductive, Perinatal, and Pediatric Epidemiology from the National Institute of Child Health and Human Development, National Institutes of Health. NR 51 TC 3 Z9 3 U1 0 U2 2 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 2015 VL 24 IS 8 BP 1214 EP 1221 DI 10.1158/1055-9965.EPI-15-0172 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CO7DY UT WOS:000359320500010 PM 26063479 ER PT J AU Mihm, MC Mule, JJ AF Mihm, Martin C., Jr. Mule, James J. TI Reflections on the Histopathology of Tumor-Infiltrating Lymphocytes in Melanoma and the Host Immune Response SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID PRIMARY CUTANEOUS MELANOMA; ADOPTIVE CELL THERAPY; METASTATIC MELANOMA; MALIGNANT-MELANOMA; LYMPHOID STRUCTURES; PROGNOSTIC-FACTORS; SYNGENEIC TUMORS; T-LYMPHOCYTES; STAGE-I; IMMUNOTHERAPY AB In the past five decades, the role for lymphocytes in host immune response to tumors has been shown, at least in some patients, to be a critical component in disease prognosis. Also, the heterogeneity of lymphocytes has been documented, including the existence of regulatory T cells that suppress the immune response. As the functions of lymphocytes have become better defined in terms of antitumor immunity, specific targets on lymphocytes have been uncovered. The appreciation of the role of immune checkpoints has also led to therapeutic approaches that illustrate the effectiveness of blocking negative regulators of the antitumor immune response. In this Masters of Immunology article, we trace the evolution of our understanding of tumor-infiltrating lymphocytes and discuss their role in melanoma prognosis from the very basic observation of their existence to the latest manipulation of their functions with the result of improvement of the host response against the tumor. C1 [Mihm, Martin C., Jr.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. [Mule, James J.] Univ S Florida, H Lee Moffitt Canc Ctr, Translat Sci Melanoma Res & Treatment, Tampa, FL 33682 USA. RP Mihm, MC (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 41 Ave Louis Pasteur,Room 317B, Boston, MA 02115 USA. EM mmihm@partners.org; James.Mule@moffitt.org FU NCI-NIH [1 R01 CA148995, P30CA076292, P50CA168536]; V Foundation, a Cancer Research Institute grant; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation FX This work was supported in part by the NCI-NIH (1 R01 CA148995; P30CA076292; P50CA168536 to J.J. Mule), the V Foundation, a Cancer Research Institute grant (to M.C. Mihm), and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation. NR 66 TC 6 Z9 6 U1 0 U2 8 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 2015 VL 3 IS 8 BP 827 EP 835 DI 10.1158/2326-6066.CIR-15-0143 PG 9 WC Oncology; Immunology SC Oncology; Immunology GA CO7DH UT WOS:000359318100001 PM 26242760 ER PT J AU Van Allen, EM Golay, HG Liu, Y Koyama, S Wong, K Taylor-Weiner, A Giannakis, M Harden, M Rojas-Rudilla, V Chevalier, A Thai, T Lydon, C Mach, S Avila, AG Wong, JA Rabin, AR Helmkamp, J Sholl, L Carter, SL Oxnard, G Janne, P Getz, G Lindeman, N Hammerman, PS Garraway, LA Hodi, FS Rodig, SJ Dranoff, G Wong, KK Barbie, DA AF Van Allen, Eliezer M. Golay, Hadrien G. Liu, Yan Koyama, Shohei Wong, Karrie Taylor-Weiner, Amaro Giannakis, Marios Harden, Maegan Rojas-Rudilla, Vanesa Chevalier, Aaron Tran Thai Lydon, Christine Mach, Stacy Avila, Ada G. Wong, Joshua A. Rabin, Alexandra R. Helmkamp, Joshua Sholl, Lynette Carter, Scott L. Oxnard, Geoffrey Janne, Pasi Getz, Gad Lindeman, Neal Hammerman, Peter S. Garraway, Levi A. Hodi, F. Stephen Rodig, Scott J. Dranoff, Glenn Wong, Kwok-Kin Barbie, David A. TI Long-term Benefit of PD-L1 Blockade in Lung Cancer Associated with JAK3 Activation SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID ACUTE MEGAKARYOBLASTIC LEUKEMIA; INTEGRATIVE GENOMICS VIEWER; B-CELL LYMPHOMA; ANTI-PD-L1 ANTIBODY; CTLA-4 BLOCKADE; SEQUENCING DATA; TUMOR SAMPLES; MUTATIONS; EXPRESSION; EVEROLIMUS AB PD-1 immune checkpoint blockade occasionally results in durable clinical responses in advanced metastatic cancers. However, mechanism-based predictors of response to this immunotherapy remain incompletely characterized. We performed comprehensive genomic profiling on a tumor and germline sample from a patient with refractory lung adenocarcinoma who achieved marked long-term clinical benefit from anti-PD-L1 therapy. We discovered activating somatic and germline amino acid variants in JAK3 that promoted PD-L1 induction in lung cancer cells and in the tumor immune microenvironment. These findings suggest that genomic alterations that deregulate cytokine receptor signal transduction could contribute to PD-L1 activation and engagement of the PD-1 immune checkpoint in lung cancer. C1 [Van Allen, Eliezer M.; Golay, Hadrien G.; Liu, Yan; Koyama, Shohei; Wong, Karrie; Giannakis, Marios; Tran Thai; Lydon, Christine; Mach, Stacy; Avila, Ada G.; Wong, Joshua A.; Rabin, Alexandra R.; Helmkamp, Joshua; Oxnard, Geoffrey; Janne, Pasi; Hammerman, Peter S.; Garraway, Levi A.; Hodi, F. Stephen; Dranoff, Glenn; Wong, Kwok-Kin; Barbie, David A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Van Allen, Eliezer M.; Taylor-Weiner, Amaro; Giannakis, Marios; Harden, Maegan; Chevalier, Aaron; Carter, Scott L.; Getz, Gad; Hammerman, Peter S.; Garraway, Levi A.; Barbie, David A.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Rojas-Rudilla, Vanesa; Sholl, Lynette; Lindeman, Neal; Rodig, Scott J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Janne, Pasi; Wong, Kwok-Kin] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA USA. [Getz, Gad] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Hodi, F. Stephen; Rodig, Scott J.; Dranoff, Glenn] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Immunooncol, Boston, MA 02115 USA. RP Barbie, DA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave D819, Boston, MA 02215 USA. EM kwong1@partners.org; dbarbie@partners.org OI Koyama, Shohei/0000-0002-6897-9417 FU American Cancer Society; U.S. NIH [R01 CA122794, R01 CA166480, R01 CA163896, R01CA140594, U01CA141576]; Thoracic Foundation [K08 CA138918-01A1]; Uniting Against Lung Cancer; GTM Fund for Lung Cancer Research; Damon Runyon Cancer Research Foundation FX This work was supported by the American Cancer Society (to E.M. Van Allen.), U.S. NIH R01 CA122794, R01 CA166480, R01 CA163896, R01CA140594, and U01CA141576 (to K.-K. Wong), the Thoracic Foundation (to K.-K. Wong), K08 CA138918-01A1 (to D.A. Barbie), Uniting Against Lung Cancer (to K.-K. Wong and D.A. Barbie), the GTM Fund for Lung Cancer Research (to D.A. Barbie), and the Damon Runyon Cancer Research Foundation (to P.S. Hammerman). NR 45 TC 10 Z9 10 U1 0 U2 7 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 2015 VL 3 IS 8 BP 855 EP 863 DI 10.1158/2326-6066.CIR-15-0024 PG 9 WC Oncology; Immunology SC Oncology; Immunology GA CO7DH UT WOS:000359318100006 PM 26014096 ER PT J AU Srivastava, RM Trivedi, S Concha-Benavente, F Hyun-Bae, J Wang, L Seethala, RR Branstetter, BF Ferrone, S Ferris, RL AF Srivastava, Raghvendra M. Trivedi, Sumita Concha-Benavente, Fernando Hyun-Bae, Jie Wang, Lin Seethala, Raja R. Branstetter, Barton F. Ferrone, Soldano Ferris, Robert L. TI STAT1-Induced HLA Class I Upregulation Enhances Immunogenicity and Clinical Response to Anti-EGFR mAb Cetuximab Therapy in HNC Patients SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID MHC CLASS-I; SQUAMOUS-CELL CARCINOMA; EPIDERMAL-GROWTH-FACTOR; NECK-CANCER PATIENTS; GENE-EXPRESSION; PROCESSING MACHINERY; NATURAL-KILLER; IMMUNE ESCAPE; HEAD; TUMOR AB The goal of this study was to characterize the molecular mechanisms underlying cetuximab-mediated upregulation of HLA class I antigen-processing machinery components in head and neck cancer (HNC) cells and to determine the clinical significance of these changes in cetuximab-treated HNC patients. Flow cytometry, signaling studies, and chromatin immunoprecipitation (ChIP) assays were performed using HNC cells treated with cetuximab alone or with Fc gamma receptor (Fc gamma R)-bearing lymphocytes to establish the mechanism of EGFR-dependent regulation of HLA APM expression. A prospective phase II clinical trial of neoadjuvant cetuximab was used to correlate HLA class I expression with clinical response in HNC patients. EGFR blockade triggered STAT1 activation and HLA upregulation, in a src homology-containing protein (SHP)-2-dependent fashion, more prominently in HLA-B/C than in HLA-A alleles. EGFR signaling blockade also enhanced IFN gamma receptor 1 (IFNAR) expression, augmenting induction of HLA class I and TAP1/2 expression by IFN gamma, which was abrogated in STAT1(-/-) cells. Cetuximab enhanced HNC cell recognition by EGFR853-861-specific CTLs, and notably enhanced surface presentation of a non-EGFR peptide (MAGE-3271-279). HLA class I upregulation was significantly associated with clinical response in cetuximab-treated HNC patients. EGFR induces HLA downregulation through SHP-2/STAT1 suppression. Reversal of HLA class I downregulation was more prominent in clinical responders to cetuximab therapy, supporting an important role for adaptive immunity in cetuximab antitumor activity. Abrogating EGFR-induced immune escape mechanisms and restoring STAT1 signaling to reverse HLA downregulation using cetuximab should be combined with strategies to enhance adaptive cellular immunity. C1 [Srivastava, Raghvendra M.; Trivedi, Sumita; Hyun-Bae, Jie; Wang, Lin; Ferris, Robert L.] Univ Pittsburgh, Dept Otolaryngol, Pittsburgh, PA 15213 USA. [Concha-Benavente, Fernando; Ferris, Robert L.] Univ Pittsburgh, Dept Immunol, Pittsburgh, PA 15213 USA. [Seethala, Raja R.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA. [Branstetter, Barton F.] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15213 USA. [Ferrone, Soldano] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. [Ferris, Robert L.] Univ Pittsburgh, Inst Canc, Canc Immunol Program, Pittsburgh, PA 15213 USA. RP Ferris, RL (reprint author), Univ Pittsburgh, Hillman Canc Ctr Res Pavil, 5117 Ctr Ave,Room 2-26b, Pittsburgh, PA 15213 USA. EM ferrisrl@upmc.edu FU NIH [R01 DE19727, P50 CA097190, CA110249]; University of Pittsburgh Cancer Center support grant [P30CA047904] FX This work was supported by NIH grants R01 DE19727, P50 CA097190, and CA110249, and University of Pittsburgh Cancer Center support grant P30CA047904. NR 42 TC 9 Z9 9 U1 0 U2 2 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 2015 VL 3 IS 8 BP 936 EP 945 DI 10.1158/2326-6066.CIR-15-0053 PG 10 WC Oncology; Immunology SC Oncology; Immunology GA CO7DH UT WOS:000359318100014 PM 25972070 ER PT J AU Vuoksimaa, E Panizzon, MS Chen, CH Fiecas, M Eyler, LT Fennema-Notestine, C Hagler, DJ Fischl, B Franz, CE Jak, A Lyons, MJ Neale, MC Rinker, DA Thompson, WK Tsuang, MT Dale, AM Kremen, WS AF Vuoksimaa, Eero Panizzon, Matthew S. Chen, Chi-Hua Fiecas, Mark Eyler, Lisa T. Fennema-Notestine, Christine Hagler, Donald J. Fischl, Bruce Franz, Carol E. Jak, Amy Lyons, Michael J. Neale, Michael C. Rinker, Daniel A. Thompson, Wesley K. Tsuang, Ming T. Dale, Anders M. Kremen, William S. TI The Genetic Association Between Neocortical Volume and General Cognitive Ability Is Driven by Global Surface Area Rather Than Thickness SO CEREBRAL CORTEX LA English DT Article DE cognition; cortex; genetic correlation; heritability; twins ID HUMAN CEREBRAL-CORTEX; MAGNETIC-RESONANCE IMAGES; VIETNAM ERA TWIN; CORTICAL THICKNESS; HUMAN BRAIN; ENVIRONMENTAL-INFLUENCES; INTELLECTUAL ABILITY; PARENTAL EDUCATION; GRAY-MATTER; INTELLIGENCE AB Total gray matter volume is associated with general cognitive ability (GCA), an association mediated by genetic factors. It is expectable that total neocortical volume should be similarly associated with GCA. Neocortical volume is the product of thickness and surface area, but global thickness and surface area are unrelated phenotypically and genetically in humans. The nature of the genetic association between GCA and either of these 2 cortical dimensions has not been examined. Humans possess greater cognitive capacity than other species, and surface area increases appear to be the primary driver of the increased size of the human cortex. Thus, we expected neocortical surface area to be more strongly associated with cognition than thickness. Using multivariate genetic analysis in 515 middle-aged twins, we demonstrated that both the phenotypic and genetic associations between neocortical volume and GCA are driven primarily by surface area rather than thickness. Results were generally similar for each of 4 specific cognitive abilities that comprised the GCA measure. Our results suggest that emphasis on neocortical surface area, rather than thickness, could be more fruitful for elucidating neocortical-GCA associations and identifying specific genes underlying those associations. C1 [Vuoksimaa, Eero; Panizzon, Matthew S.; Chen, Chi-Hua; Fiecas, Mark; Eyler, Lisa T.; Fennema-Notestine, Christine; Franz, Carol E.; Jak, Amy; Rinker, Daniel A.; Thompson, Wesley K.; Tsuang, Ming T.; Kremen, William S.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Vuoksimaa, Eero; Panizzon, Matthew S.; Chen, Chi-Hua; Fiecas, Mark; Franz, Carol E.; Tsuang, Ming T.; Kremen, William S.] Univ Calif San Diego, Ctr Behav Genom, Twin Res Lab, La Jolla, CA 92093 USA. [Fennema-Notestine, Christine; Hagler, Donald J.; Rinker, Daniel A.; Dale, Anders M.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Vuoksimaa, Eero] Univ Helsinki, Dept Publ Hlth, FI-00014 Helsinki, Finland. [Eyler, Lisa T.] VA San Diego Healthcare Syst, Mental Illness Res Educ & Clin Ctr, San Diego, CA USA. [Fischl, Bruce] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Fischl, Bruce] Harvard Univ, Sch Med, Boston, MA USA. [Fischl, Bruce] MIT, Comp Sci & AI Lab, Cambridge, MA 02139 USA. [Jak, Amy; Kremen, William S.] VA San Diego Healthcare Syst, Ctr Excellence Stress & Mental Hlth, La Jolla, CA USA. [Lyons, Michael J.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Neale, Michael C.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Sch Med, Richmond, VA USA. RP Vuoksimaa, E (reprint author), Univ Helsinki, Dept Publ Hlth, POB 41 Mannerheimintie 172, FI-00014 Helsinki, Finland. EM eero.vuoksimaa@helsinki.fi OI Lyons, Michael/0000-0001-6516-9219; Fennema-Notestine, Christine/0000-0002-6527-6361 FU NIH [R01 AG018386, AG022381, AG022982, R01 AG018384]; Academy of Finland [257075]; US Department of Veterans Affairs FX This work was supported by NIH grants R01 AG018386, AG022381, AG022982 to W.S.K. and R01 AG018384 to M.J.L., and the Academy of Finland grant 257075 to E.V., and resources of the VA San Diego Center of Excellence for Stress and Mental Health Healthcare System. The Cooperative Studies Program of the US Department of Veterans Affairs provided financial support for development and maintenance of the Vietnam Era Twin (VET) Registry. NR 69 TC 13 Z9 13 U1 0 U2 13 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD AUG PY 2015 VL 25 IS 8 BP 2127 EP 2137 DI 10.1093/cercor/bhu018 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CO7DU UT WOS:000359320000011 PM 24554725 ER PT J AU Axelrod, V Bar, M Rees, G Yovel, G AF Axelrod, Vadim Bar, Moshe Rees, Geraint Yovel, Galit TI Neural Correlates of Subliminal Language Processing SO CEREBRAL CORTEX LA English DT Article DE continuous flash suppression (CFS); decoding subliminal content; fMRI imaging of unconscious processing; multivoxel pattern classification analysis (MVPA); subliminal language processing ID HUMAN VISUAL-CORTEX; CONTINUOUS FLASH SUPPRESSION; WORD FORM AREA; INTEROCULAR SUPPRESSION; HUMAN BRAIN; UNCONSCIOUS ACTIVATION; ATTENTIONAL BLINK; RIGHT-HEMISPHERE; PATTERN-ANALYSIS; FMRI AB Language is a high-level cognitive function, so exploring the neural correlates of unconscious language processing is essential for understanding the limits of unconscious processing in general. The results of several functional magnetic resonance imaging studies have suggested that unconscious lexical and semantic processing is confined to the posterior temporal lobe, without involvement of the frontal lobe-the regions that are indispensable for conscious language processing. However, previous studies employed a similarly designed masked priming paradigm with briefly presented single and contextually unrelated words. It is thus possible, that the stimulation level was insufficiently strong to be detected in the high-level frontal regions. Here, in a high-resolution fMRI and multivariate pattern analysis study we explored the neural correlates of subliminal language processing using a novel paradigm, where written meaningful sentences were suppressed from awareness for extended duration using continuous flash suppression. We found that subjectively and objectively invisible meaningful sentences and unpronounceable nonwords could be discriminated not only in the left posterior superior temporal sulcus (STS), but critically, also in the left middle frontal gyrus. We conclude that frontal lobes play a role in unconscious language processing and that activation of the frontal lobes per se might not be sufficient for achieving conscious awareness. C1 [Axelrod, Vadim; Bar, Moshe] Bar Ilan Univ, Gonda Multidisciplinary Brain Res Ctr, Ramat Gan, Israel. [Axelrod, Vadim; Rees, Geraint] UCL, UCL Inst Cognit Neurosci, London, England. [Rees, Geraint] UCL, Wellcome Trust Ctr Neuroimaging, London, England. [Bar, Moshe] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Bar, Moshe] Harvard Univ, Sch Med, Charlestown, MA USA. [Yovel, Galit] Tel Aviv Univ, Sch Psychol Sci, IL-69978 Tel Aviv, Israel. [Yovel, Galit] Tel Aviv Univ, Sagol Sch Neurosci, IL-69978 Tel Aviv, Israel. RP Axelrod, V (reprint author), Bar Ilan Univ, Gonda Multidisciplinary Brain Res Ctr, Ramat Gan, Israel. EM vadim.axelrod@gmail.com RI Rees, Geraint/C-1493-2008 OI Rees, Geraint/0000-0002-9623-7007 FU Israeli Center of Research Excellence in Cognitive Sciences; Daniel Turnberg Travel Fellowship; Wellcome Trust [100227/Z/12/Z, 091593/Z/10/Z] FX This study was supported by the Israeli Center of Research Excellence in Cognitive Sciences (V.A., M.B., and G.Y.), Daniel Turnberg Travel Fellowship (V.A.) and the Wellcome Trust (G.R.). Funding to pay the Open Access publication charges for this article was provided by Wellcome Trust grant 100227/Z/12/Z and Wellcome Trust strategic award 091593/Z/10/Z. NR 77 TC 4 Z9 4 U1 7 U2 16 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD AUG PY 2015 VL 25 IS 8 BP 2160 EP 2169 DI 10.1093/cercor/bhu022 PG 10 WC Neurosciences SC Neurosciences & Neurology GA CO7DU UT WOS:000359320000014 PM 24557638 ER PT J AU Mylonakis, E Clancy, CJ Ostrosky-Zeichner, L Garey, KW Alangaden, GJ Vazquez, JA Groeger, JS Judson, MA Vinagre, YM Heard, SO Zervou, FN Zacharioudakis, IM Kontoyiannis, DP Pappas, PG AF Mylonakis, Eleftherios Clancy, Cornelius J. Ostrosky-Zeichner, Luis Garey, Kevin W. Alangaden, George J. Vazquez, Jose A. Groeger, Jeffrey S. Judson, Marc A. Vinagre, Yuka-Marie Heard, Stephen O. Zervou, Fainareti N. Zacharioudakis, Ioannis M. Kontoyiannis, Dimitrios P. Pappas, Peter G. TI When Diagnostic Technology Is Ahead of the Hospital Budget: What Is Antimicrobial Stewardship to Do? Reply SO CLINICAL INFECTIOUS DISEASES LA English DT Letter ID CANDIDEMIA; IMPACT; RISK C1 [Mylonakis, Eleftherios; Zervou, Fainareti N.; Zacharioudakis, Ioannis M.] Brown Univ, Rhode Isl Hosp, Div Infect Dis, Warren Alpert Med Sch, Providence, RI 02903 USA. [Clancy, Cornelius J.] Univ Pittsburgh, Div Infect Dis, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. [Ostrosky-Zeichner, Luis] Univ Texas Houston, Sch Med, Div Infect Dis, Houston, TX USA. [Ostrosky-Zeichner, Luis] Mem Hermann Texas Med Ctr, Houston, TX USA. [Garey, Kevin W.] Univ Houston, Coll Pharm, Houston, TX 77004 USA. [Alangaden, George J.] Henry Ford Hlth Syst, Div Infect Dis, Detroit, MI USA. [Vazquez, Jose A.] Georgia Regents Univ, Med Coll Georgia, Dept Med, Augusta, GA USA. [Groeger, Jeffrey S.] Mem Sloan Kettering Canc Ctr, Urgent Care Serv, New York, NY 10021 USA. [Judson, Marc A.] Albany Med, Div Pulm & Crit Care Med, New York, NY USA. [Vinagre, Yuka-Marie] St Vincent Hosp, Dept Crit Care Med, Worcester, MA 01604 USA. [Heard, Stephen O.] UMass Mem Med Ctr, Dept Anesthesiol, Worcester, MA USA. [Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Dept Infect Dis Infect Control & Employee Hlth, Houston, TX 77030 USA. [Pappas, Peter G.] Univ Alabama Birmingham, Div Infect Dis, Birmingham, AL USA. RP Mylonakis, E (reprint author), Brown Univ, Rhode Isl Hosp, Div Infect Dis, Warren Alpert Med Sch, 593 Eddy St,3rd Floor,Ste 328-330, Providence, RI 02903 USA. EM emylonakis@lifespan.org NR 10 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG 1 PY 2015 VL 61 IS 3 BP 487 EP 488 DI 10.1093/cid/civ357 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CO7MM UT WOS:000359343500030 PM 25944341 ER PT J AU Basu, PP James, N AF Basu, P. Patrick James, Niraj TI Clinical and Neurologic Manifestation of Minimal Hepatic Encephalopathy and Overt Hepatic Encephalopathy SO CLINICS IN GERIATRIC MEDICINE LA English DT Article DE Neurologic manifestation; Minimal hepatic encephalopathy; MHE; Overt hepatic encephalopathy; OHE ID SLEEP DISTURBANCE; LIVER-CIRRHOSIS; MELATONIN; HYPERAMMONEMIA; INFLAMMATION; IMPAIRMENT; PREVALENCE; MECHANISMS; DIAGNOSIS; FAILURE AB Hepatic encephalopathy (HE) shows a wide spectrum of neuropsychiatric manifestations. A combined effort with neuropsychological and psychometric evaluation has to be performed to recognize the syndrome, whereas minimal HE (MHE) is largely under-recognized. Subtle symptoms of MHE can only be diagnosed through specialized neuropsychiatric testing. Early diagnosis and treatment may drastically improve the quality of life for many cirrhotic patients. Further research to gain better insight into the pathophysiology and diagnostic accuracy of HE will help determine future management strategies. C1 [Basu, P. Patrick] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. [Basu, P. Patrick] Kings Cty Hosp Med Ctr, Dept Med, Brooklyn, NY 11203 USA. [James, Niraj] Icahn Sch Med Mt Sinai, Dept Med, James J Peters VA Med Ctr, New York, NY 10468 USA. RP James, N (reprint author), Icahn Sch Med Mt Sinai, Dept Med, James J Peters VA Med Ctr, 130 West Kingsbridge Rd, New York, NY 10468 USA. EM nirajjames@gmail.com NR 52 TC 0 Z9 0 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0690 EI 1879-8853 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD AUG PY 2015 VL 31 IS 3 BP 461 EP + DI 10.1016/j.cld.2015.05.003 PG 13 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA CO9PK UT WOS:000359507500003 PM 26195201 ER PT J AU Anzueto, A AF Anzueto, Antonio TI Alpha-1 Antitrypsin Deficiency-Associated Chronic Obstructive Pulmonary Disease: A Family Perspective SO COPD-JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE LA English DT Editorial Material DE augmentation therapy; caregiver; chronic bronchitis; emphysema ID QUALITY-OF-LIFE; HEREDITARY ALPHA(1)-ANTITRYPSIN DEFICIENCY; AUGMENTATION THERAPY; MULTIPLE-SCLEROSIS; ANTITRYPSIN DEFICIENCY; LUNG-FUNCTION; PI-TYPES; INDIVIDUALS; HYPERTENSION; DENSITOMETRY AB Alpha-1 antitrypsin (AAT) deficiency (AATD) is a genetic condition that can lead to the early onset of chronic obstructive pulmonary disease (COPD), a disorder that comprises elements of chronic bronchitis and emphysema. AATD is characterized by reduced levels of the AAT protease inhibitor, leading to unrestricted protease activity in the lung, which promotes destruction of lung tissue. In severe cases, patients with AATD have an increased mortality risk and, potentially, a poor quality of life due to more frequent COPD exacerbations and/or limitations on daily activity. However, the burden of AATD on members of the patient's immediate family who may serve as caregivers has not been described. Because the age range at which most patients are diagnosed with AATD may affect the economic status of an individual and/or of a family, it is likely that a diagnosis of AATD may have negative effects that extend beyond those on the diagnosed person to include immediate family members. Here, we review the literature to investigate the impact of the caregiver role of family members in disease states that affect an age group similar to AATD. Furthermore, we provide a case study showing the effect of AATD on immediate family members. C1 [Anzueto, Antonio] Audie L Murphy Mem Vet Adm Med Ctr, South Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Anzueto, A (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Pulm Dis, Suite 111E,7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM anzueto@uthscsa.edu NR 39 TC 1 Z9 1 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1541-2555 EI 1541-2563 J9 COPD JI COPD-J. Chronic Obstr. Pulm. Dis. PD AUG PY 2015 VL 12 IS 4 BP 462 EP 467 DI 10.3109/15412555.2014.974746 PG 6 WC Respiratory System SC Respiratory System GA CP4JY UT WOS:000359849000014 PM 25474273 ER PT J AU Lee, KC Eisen, DB AF Lee, Kachiu C. Eisen, Daniel B. TI Commentary on Laboratory Errors Leading to Nonmelanoma Skin Cancer Recurrence Following Mohs Micrographic Surgery SO DERMATOLOGIC SURGERY LA English DT Editorial Material ID BASAL-CELL CARCINOMA; INCOMPLETE EXCISION; TUMOR RECURRENCE; INFLAMMATION; CONCORDANCE C1 [Lee, Kachiu C.] Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA. [Eisen, Daniel B.] Univ Calif Davis, Med Ctr, Dept Dermatol, Sacramento, CA 95817 USA. RP Lee, KC (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 15 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1076-0512 EI 1524-4725 J9 DERMATOL SURG JI Dermatol. Surg. PD AUG PY 2015 VL 41 IS 8 BP 917 EP 918 DI 10.1097/DSS.0000000000000436 PG 2 WC Dermatology; Surgery SC Dermatology; Surgery GA CP1MS UT WOS:000359640500008 PM 26166261 ER PT J AU Keeling, BH Whitsitt, J Liu, A Dunnick, CA AF Keeling, Brett H. Whitsitt, Jacob Liu, Arthur Dunnick, Cory A. TI Keloid Removal by Shave Excision With Adjuvant External Beam Radiation Therapy SO DERMATOLOGIC SURGERY LA English DT Letter C1 [Keeling, Brett H.] Texas So Univ, Dept Dermatol, Austin, TX 78712 USA. [Whitsitt, Jacob] Univ Colorado, Sch Med, Aurora, CO USA. [Liu, Arthur] Univ Colorado, Dept Radiat Oncol, Aurora, CO USA. [Dunnick, Cory A.] Univ Colorado, Dept Dermatol, Aurora, CO USA. [Dunnick, Cory A.] Denver VA Med Ctr, Dermatol Serv, Denver, CO USA. RP Keeling, BH (reprint author), Texas So Univ, Dept Dermatol, Austin, TX 78712 USA. NR 5 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1076-0512 EI 1524-4725 J9 DERMATOL SURG JI Dermatol. Surg. PD AUG PY 2015 VL 41 IS 8 BP 989 EP 992 DI 10.1097/DSS.0000000000000417 PG 4 WC Dermatology; Surgery SC Dermatology; Surgery GA CP1MS UT WOS:000359640500023 PM 26132894 ER PT J AU Zheng, XF Kalev, P Chowdhury, D AF Zheng, Xiao-Feng Kalev, Peter Chowdhury, Dipanjan TI Emerging role of protein phosphatases changes the landscape of phospho-signaling in DNA damage response SO DNA REPAIR LA English DT Article DE Protein phosphatase; Dephosphorylation; ATM; KAP1; CTIP; EXO1; 53BP1; XRCC4; YEN1; BLM ID STRAND BREAK REPAIR; HOLLIDAY JUNCTION RESOLVASE; CELL-CYCLE REGULATION; HOMOLOGOUS RECOMBINATION; END RESECTION; KAP-1 PHOSPHORYLATION; WIP1 PHOSPHATASE; TUMOR-SUPPRESSOR; GENOME STABILITY; PATHWAY CHOICE AB Phosphorylation signaling networks have primarily been studied from an activation perspective, with protein phosphatases viewed as simple counter-balances that functioned passively in the wake of kinase activity. Indeed, there have been only sporadic efforts to investigate the independent role of phosphatases in DNA damage response (DDR). However, global phosphoproteomic analysis of the DDR revealed that over one-third of observed phosphorylation sites were down-regulated within minutes of DNA damage, suggesting a more robust role for phosphatases in DNA repair. Consistent with these observations, recent studies reveal that dephosphorylation of DNA repair factors during specific phases of the cell cycle may be a pre-requisite for their participation in the DDR. Here, we summarize recent literature and speculate on the emerging role of phosphatases in the DDR. (C) 2015 Elsevier B.V. All rights reserved. C1 [Zheng, Xiao-Feng; Kalev, Peter; Chowdhury, Dipanjan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Chowdhury, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM dipanjan_chowdhury@dfci.harvard.edu FU American Cancer Society [PF-14-181-01-DMC]; Claudia Adam Barr Grant; Leukemia and Lymphoma Society Scholar Award; Mary Kay Foundation FX We apologize to our colleagues whose work we could not acknowledge owing to space constraints. XFZ is supported by Post-doctoral Fellowship PF-14-181-01-DMC from the American Cancer Society. DC is supported by Claudia Adam Barr Grant, Leukemia and Lymphoma Society Scholar Award and the Mary Kay Foundation. NR 87 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 EI 1568-7856 J9 DNA REPAIR JI DNA Repair PD AUG PY 2015 VL 32 SI SI BP 58 EP 65 DI 10.1016/j.dnarep.2015.04.014 PG 8 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA CO4ZN UT WOS:000359169500009 PM 25956864 ER PT J AU Geffrey, AL Pollack, SF Bruno, PL Thiele, EA AF Geffrey, Alexandra L. Pollack, Sarah F. Bruno, Patricia L. Thiele, Elizabeth A. TI Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy SO EPILEPSIA LA English DT Article DE Antiepileptic drugs; Cannabis; Treatment-resistant epilepsy; Cytochrome P450 pathway; Norclobazam ID IN-VITRO; CYTOCHROME-P450 ENZYMES; SEIZURES; METABOLISM; RATS; MICE; INHIBITION; CYP2C19; VIVO AB ObjectiveUnder an expanded access investigational new drug (IND) trial, cannabidiol (CBD) is being studied as a possible adjuvant treatment of refractory epilepsy in children. Of the 25 subjects in the trial, 13 were being treated with clobazam (CLB). Because CLB and CBD are both metabolized in the cytochrome P450 (CYP) pathway, we predicted a drug-drug interaction, which we evaluate in this article. MethodsThirteen subjects with refractory epilepsy concomitantly taking CLB and CBD under IND 119876 were included in this study. Demographic information was collected for each subject including age, sex, and etiology of seizures, as well as concomitant antiepileptic drugs (AEDs). CLB, N-desmethylclobazam (norclobazam; nCLB), and CBD levels were measured over the course of CBD treatment. CLB doses were recorded at baseline and at weeks 4 and 8 of CBD treatment. Side effects were monitored. ResultsWe report elevated CLB and nCLB levels in these subjects. The mean (standard deviation [SD]) increase in CLB levels was 60 +/- 80% (95% confidence interval (CI) [-2-91%] at 4weeks); the mean increase in nCLB levels was 500 +/- 300% (95% CI [+90-610%] at 4weeks). Nine of 13 subjects had a >50% decrease in seizures, corresponding to a responder rate of 70%. The increased CLB and nCLB levels and decreases in seizure frequency occurred even though, over the course of CBD treatment, CLB doses were reduced for 10 (77%) of the 13 subjects. Side effects were reported in 10 (77%) of the 13 subjects, but were alleviated with CLB dose reduction. SignificanceMonitoring of CLB and nCLB levels is necessary for clinical care of patients concomitantly on CLB and CBD. Nonetheless, CBD is a safe and effective treatment of refractory epilepsy in patients receiving CLB treatment. C1 [Geffrey, Alexandra L.; Pollack, Sarah F.; Bruno, Patricia L.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Thiele, EA (reprint author), Massachusetts Gen Hosp, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM ethiele@partners.org FU Pediatric Epilepsy Program at Massachusetts General Hospital FX The Pediatric Epilepsy Program at Massachusetts General Hospital supported this study and GW Pharmaceuticals provided Epidiolex. Thank you also to Gary Yellen, PhD, for assistance with data analysis. NR 24 TC 23 Z9 23 U1 2 U2 25 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 EI 1528-1167 J9 EPILEPSIA JI Epilepsia PD AUG PY 2015 VL 56 IS 8 BP 1246 EP 1251 DI 10.1111/epi.13060 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA CO2AX UT WOS:000358958700010 PM 26114620 ER PT J AU Alvarez, V Lee, JW Drislane, FW Westover, MB Novy, J Dworetzky, BA Rossetti, AO AF Alvarez, Vincent Lee, Jong Woo Drislane, Frank W. Westover, M. Brandon Novy, Jan Dworetzky, Barbara A. Rossetti, Andrea O. TI Practice variability and efficacy of clonazepam, lorazepam, and midazolam in status epilepticus: A multicenter comparison SO EPILEPSIA LA English DT Article DE Epilepsy; Benzodiazepines; Critical care; Coma; Neurologic emergency ID CONVULSIVE STATUS EPILEPTICUS; REFRACTORY STATUS EPILEPTICUS; INTRAVENOUS CLONAZEPAM; MANAGEMENT; ADULTS; PHARMACOKINETICS; PROGNOSIS; MORTALITY; BENZODIAZEPINES; GUIDELINES AB ObjectiveBenzodiazepines (BZD) are recommended as first-line treatment for status epilepticus (SE), with lorazepam (LZP) and midazolam (MDZ) being the most widely used drugs and part of current treatment guidelines. Clonazepam (CLZ) is also utilized in many countries; however, there is no systematic comparison of these agents for treatment of SE to date. MethodsWe identified all patients treated with CLZ, LZP, or MDZ as a first-line agent from a prospectively collected observational cohort of adult patients treated for SE in four tertiary care centers. Relative efficacies of CLZ, LZP, and MDZ were compared by assessing the risk of developing refractory SE and the number of antiseizure drugs (ASDs) required to control SE. ResultsAmong 177 patients, 72 patients (40.62%) received CLZ, 82 patients (46.33%) LZP, and 23 (12.99%) MDZ; groups were similar in demographics and SE characteristics. Loading dose was considered insufficient in the majority of cases for LZP, with a similar rate (84%, 95%, and 87.5%) in the centers involved, and CLZ was used as recommended in 52% of patients. After adjustment for relevant variables, LZP was associated with an increased risk of refractoriness as compared to CLZ (odds ratio [OR] 6.4, 95% confidence interval [CI] 2.66-15.5) and with an increased number of ASDs needed for SE control (OR 4.35, 95% CI 1.8-10.49). SignificanceCLZ seems to be an effective alternative to LZP and MDZ. LZP is frequently underdosed in this setting. These findings are highly relevant, since they may impact daily practice. C1 [Alvarez, Vincent; Lee, Jong Woo; Dworetzky, Barbara A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Alvarez, Vincent; Westover, M. Brandon] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Alvarez, Vincent; Drislane, Frank W.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Neurol, Sch Med, Boston, MA 02215 USA. [Alvarez, Vincent] Valais Hosp, Dept Neurol, Sion, Switzerland. [Novy, Jan; Rossetti, Andrea O.] CHU Vaudois, Dept Clin Neurosci, Lausanne, Switzerland. [Novy, Jan; Rossetti, Andrea O.] Univ Lausanne, Lausanne, Switzerland. RP Alvarez, V (reprint author), Valais Hosp Serv Neurol, Av Grand Champsec 80, CH-1950 Sion, Switzerland. EM vincent.alvarez@hopitalvs.ch RI Rossetti, Andrea/A-6712-2008; OI Rossetti, Andrea/0000-0002-7878-172X; Dworetzky, Barbara/0000-0002-3364-2347; Novy, Jan/0000-0002-6862-7083 FU Swiss National Science Foundation [P2GEP3_148510]; Gottfried und Julia Bangerter-Rhyner Foundation; UCB, Inc; Duke Clinical Research Institute; Sunovion, Inc.; American Brain Foundation; U.S. Food and Drug Administration (FDA); Epilepsy Foundation; American Epilepsy Society; Swiss National Scientific Fund [CR32I3_143780]; Sage Therapeutics; UCB Pharma FX Dr. Alvarez was funded by the Swiss National Science Foundation, grant: P2GEP3_148510 and the Gottfried und Julia Bangerter-Rhyner Foundation during the study period. Dr. Jong W. Lee has received research funding from UCB, Inc, the Duke Clinical Research Institute, and Sunovion, Inc. Dr Drislane has no disclosures with regard to this work. Dr. M Brandon Westover has received research funding from the American Brain Foundation. Dr Novy has recieved travel support by UCB and Pfizer. Dr. Barbara A. Dworetzky has received research funding from the U.S. Food and Drug Administration (FDA), the Epilepsy Foundation, and the American Epilepsy Society. She is a consultant for Sleep Med. and Best Doctors. Dr. Rossetti receives research support from the Swiss National Scientific Fund (CR32I3_143780), and received research support from Sage Therapeutics and UCB Pharma. NR 37 TC 11 Z9 11 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 EI 1528-1167 J9 EPILEPSIA JI Epilepsia PD AUG PY 2015 VL 56 IS 8 BP 1275 EP 1285 DI 10.1111/epi.13056 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA CO2AX UT WOS:000358958700013 PM 26140660 ER PT J AU Ruparelia, N Godec, J Lee, R Chai, JT Dall'Armellina, E McAndrew, D Digby, JE Forfar, JC Prendergast, BD Kharbanda, RK Banning, AP Neubauer, S Lygate, CA Channon, KM Haining, NW Choudhury, RP AF Ruparelia, Neil Godec, Jernej Lee, Regent Chai, Joshua T. Dall'Armellina, Erica McAndrew, Debra Digby, Janet E. Forfar, J. Colin Prendergast, Bernard D. Kharbanda, Rajesh K. Banning, Adrian P. Neubauer, Stefan Lygate, Craig A. Channon, Keith M. Haining, Nicholas W. Choudhury, Robin P. TI Acute myocardial infarction activates distinct inflammation and proliferation pathways in circulating monocytes, prior to recruitment, and identified through conserved transcriptional responses in mice and humans SO EUROPEAN HEART JOURNAL LA English DT Article DE Acute myocardial infarction; Monocytes; Genomics; Inflammation; Mitosis ID SET ENRICHMENT ANALYSIS; HUMAN PERIPHERAL-BLOOD; GENE-EXPRESSION; CARDIOVASCULAR EVENTS; SPLENIC RESERVOIR; T-CELLS; SUBSETS; PROFILES; THERAPY; ATHEROSCLEROSIS AB Aims Monocytes play critical roles in tissue injury and repair following acute myocardial infarction (AMI). Specifically targeting inflammatory monocytes in experimental models leads to reduced infarct size and improved healing. However, data from humans are sparse, and it remains unclear whether monocytes play an equally important role in humans. The aim of this study was to investigate whether the monocyte response following AMI is conserved between humans and mice and interrogate patterns of gene expression to identify regulated functions. Methods and results Thirty patients (AMI) and 24 control patients (stable coronary atherosclerosis) were enrolled. Female C57BL/6J mice (n = 6/group) underwent AMI by surgical coronary ligation. Myocardial injury was quantified by magnetic resonance imaging (human) and echocardiography (mice). Peripheral monocytes were isolated at presentation and at 48 h. RNA from separated monocytes was hybridized to Illumina beadchips. Acute myocardial infarction resulted in a significant peripheral monocytosis in both species that positively correlated with the extent of myocardial injury. Analysis of the monocyte transcriptome following AMI demonstrated significant conservation and identified inflammation and mitosis as central processes to this response. These findings were validated in both species. Conclusions Our findings show that the monocyte transcriptome is conserved between mice and humans following AMI. Patterns of gene expression associated with inflammation and proliferation appear to be switched on prior to their infiltration of injured myocardium suggesting that the specific targeting of inflammatory and proliferative processes in these immune cells in humans are possible therapeutic strategies. Importantly, they could be effective in the hours after AMI. C1 [Ruparelia, Neil; Lee, Regent; Chai, Joshua T.; Dall'Armellina, Erica; McAndrew, Debra; Digby, Janet E.; Neubauer, Stefan; Lygate, Craig A.; Channon, Keith M.; Choudhury, Robin P.] Univ Oxford, John Radcliffe Hosp, Div Cardiovasc Med, Radcliffe Dept Med, Oxford OX3 9DU, England. [Ruparelia, Neil; Forfar, J. Colin; Prendergast, Bernard D.; Kharbanda, Rajesh K.; Banning, Adrian P.; Channon, Keith M.; Choudhury, Robin P.] John Radcliffe Hosp, Oxford Heart Ctr, Oxford OX3 9DU, England. [Godec, Jernej; Haining, Nicholas W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Dall'Armellina, Erica; Choudhury, Robin P.] Univ Oxford, John Radcliffe Hosp, Acute Vasc Imaging Ctr, Radcliffe Dept Med, Oxford OX3 9DU, England. RP Choudhury, RP (reprint author), Univ Oxford, John Radcliffe Hosp, Div Cardiovasc Med, Radcliffe Dept Med, Headley Way, Oxford OX3 9DU, England. EM robin.choudhury@cardiov.ox.ac.uk OI Lee, Regent/0000-0001-8621-5165; Kharbanda, Rajesh/0000-0002-5356-2395 FU Wellcome Trust; British Heart Foundation; National Institutes of Health (NIH); National Institute for Health Research (NIHR) Oxford Biomedical Research Centre FX This work is supported by the Wellcome Trust, the British Heart Foundation, the National Institutes of Health (NIH), and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre. There are no relationships with industry. Funding to pay the Open Access publication charges for this article was provided by The Wellcome Trust. NR 50 TC 11 Z9 11 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG 1 PY 2015 VL 36 IS 29 BP 1923 EP 1934 DI 10.1093/eurheartj/ehv195 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CP1XB UT WOS:000359669800012 PM 25982896 ER PT J AU Choi, HJ Sun, D Jakobs, TC AF Choi, Hee Joo Sun, Daniel Jakobs, Tatjana C. TI Isolation of intact astrocytes from the optic nerve head of adult mice SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE Astrocytes; Mouse; Optic nerve head; Piezo; Single-cell analysis; Single-cell isolation; TRPP ID GLUTAMATE-RECEPTOR SUBUNITS; GENE-EXPRESSION; REACTIVE ASTROGLIOSIS; INTRAOCULAR-PRESSURE; RAT GLAUCOMA; DBA/2J MICE; GLIAL-CELLS; MOUSE; TRANSCRIPTOME; INJURY AB The astrocytes of the optic nerve head are a specialized subtype of white matter astrocytes that form the direct cellular environment of the unmyelinated ganglion cell axons. Due to their potential involvement in glaucoma, these astrocytes have become a target of research. Due to the heterogeneity of the optic nerve tissue, which also contains other cell types, in some cases it may be desirable to conduct gene expression studies on small numbers of well-characterized astrocytes or even individual cells. Here, we describe a simple method to isolate individual astrocytes. This method permits obtaining astrocytes with intact morphology from the adult mouse optic nerve and reduces contamination of the isolated astrocytes by other cell types. Individual astrocytes can be recognized by their morphology and collected under microscopic control. The whole procedure can be completed in 2-3 h. We also discuss downstream applications like multiplex single-cell PCR and quantitative PCR (qPCR). (C) 2015 Elsevier Ltd. All rights reserved. C1 [Choi, Hee Joo; Sun, Daniel; Jakobs, Tatjana C.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Jakobs, TC (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM Tatjana_Jakobs@meei.harvard.edu OI Jakobs, Tatjana/0000-0002-8104-9206 FU NIH [EY019703, EY022092]; Lefler Foundation from Harvard Medical School FX This work was supported by NIH grants EY019703 and EY022092, and the Lefler Foundation from Harvard Medical School. The authors thank Meredith Gregory-Ksander, PhD, for critically reading the manuscript. NR 47 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 EI 1096-0007 J9 EXP EYE RES JI Exp. Eye Res. PD AUG PY 2015 VL 137 BP 103 EP 110 DI 10.1016/j.exer.2015.06.014 PG 8 WC Ophthalmology SC Ophthalmology GA CO5CI UT WOS:000359176800013 PM 26093274 ER PT J AU Qazi, Y Kheirkhah, A Blackie, C Cruzat, A Trinidad, M Williams, C Korb, DR Hamrah, P AF Qazi, Y. Kheirkhah, A. Blackie, C. Cruzat, A. Trinidad, M. Williams, C. Korb, D. R. Hamrah, P. TI In vivo detection of clinically non-apparent ocular surface inflammation in patients with meibomian gland dysfunction-associated refractory dry eye symptoms: a pilot study SO EYE LA English DT Article ID SCANNING CONFOCAL MICROSCOPY; INTERNATIONAL WORKSHOP; PALPEBRAL CONJUNCTIVA; DISEASE INDEX; TOPICAL AZITHROMYCIN; IMPRESSION CYTOLOGY; NERVOUS-SYSTEM; HUMAN CORNEA; INNERVATION; SUBCOMMITTEE AB Purpose The utility of in vivo confocal microscopy (IVCM) in the investigation of palpebral conjunctival and corneal inflammation in patients with meibomian gland dysfunction (MGD)-associated refractory dry eye symptoms following gland expression, despite objective clinical improvement. Methods A retrospective, observational pilot study was conducted evaluating five patients with MGD-associated refractory dry eye symptoms and three control groups: symptomatic untreated MGD patients (n = 3), treatment-responsive MGD patients with improved symptoms (n = 3) and asymptomatic healthy normals (n = 11). Ocular surface disease index (OSDI) scores, tear break-up time (TBUT), the number of meibomian glands yielding liquid secretion (MGYLS), palpebral conjunctival epithelial and substantia propria immune cell (EIC, SIC), and corneal dendritic cell (DC) densities were measured. Results Despite clinical improvement (TBUT: 6.4 +/- 1.2 s to 10.1 +/- 2.1 s, P = 0.03; MGYLS: 3.5 +/- 0.8 glands to 7.0 +/- 1.1 glands, P = 0.13) and a normal clinical examination post treatment, MGD patients remained symptomatic. IVCM revealed increased immune cells in the palpebral conjunctiva (refractory MGD EIC = 592.6 +/- 110.1 cells/mm(2); untreated MGD EIC = 522.6 +/- 104.7 cells/mm(2), P = 0.69; responsive MGD EIC = 194.9 +/- 119.4 cells/mm(2), P<0.01; normals EIC = 123.7 +/- 19.2 cells/mm(2), P<0.001), but not the cornea (refractory MGD DC = 60.9 +/- 28.3 cells/mm(2); normals DC = 25.9 +/- 6.3 cells/mm(2); P = 0.43). EIC did not correlate with TBUT (R-s = -0.26, P = 0.33). OSDI scores correlated with both EIC (R-s = 0.76, P<0.001) and TBUT (R-s = -0.69, P<0.01) but not SIC. Intraglandular immune cells were also seen. Conclusion MGD-associated refractory symptoms and the symptom-sign disparity may be explained by clinically non-apparent, active inflammation of the palpebral conjunctiva as detected by IVCM. These patients may benefit from anti-inflammatory therapy. C1 [Qazi, Y.; Kheirkhah, A.; Cruzat, A.; Trinidad, M.; Williams, C.; Hamrah, P.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Surface Imaging Ctr,Cornea Serv,Dept Ophth, Boston, MA 02114 USA. [Blackie, C.; Korb, D. R.] Korb Associates, Boston, MA USA. RP Hamrah, P (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Surface Imaging Ctr,Cornea Serv,Dept Ophth, 243 Charles St, Boston, MA 02114 USA. EM pedram_hamrah@meei.harvard.edu OI Hamrah, Pedram/0000-0002-9313-2939 FU NIH [K08-EY020575, L30-EY021919]; Falk Medical Research Foundation; Research to Prevent Blindness Career Development Award FX The work presented in this article was supported by NIH K08-EY020575 (PH), NIH L30-EY021919 (PH), Falk Medical Research Foundation (PH), and Research to Prevent Blindness Career Development Award (PH). The funding organizations had no role in the design or conduct of this research. NR 52 TC 6 Z9 7 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X EI 1476-5454 J9 EYE JI Eye PD AUG PY 2015 VL 29 IS 8 BP 1099 EP 1110 DI 10.1038/eye.2015.103 PG 12 WC Ophthalmology SC Ophthalmology GA CO9GF UT WOS:000359481500016 PM 26088680 ER PT J AU Nag, A Vigneau, S Savova, V Zwemer, LM Gimelbrant, AA AF Nag, Anwesha Vigneau, Sebastien Savova, Virginia Zwemer, Lillian M. Gimelbrant, Alexander A. TI Chromatin Signature Identifies Monoallelic Gene Expression Across Mammalian Cell Types SO G3-GENES GENOMES GENETICS LA English DT Article DE gene expression; epigenetics; chromatin ID RNA-SEQ; GENOME; MOUSE; STATE AB Monoallelic expression of autosomal genes (MAE) is a widespread epigenetic phenomenon which is poorly understood, due in part to current limitations of genome-wide approaches for assessing it. Recently, we reported that a specific histone modification signature is strongly associated with MAE and demonstrated that it can serve as a proxy of MAE in human lymphoblastoid cells. Here, we use murine cells to establish that this chromatin signature is conserved between mouse and human and is associated with MAE in multiple cell types. Our analyses reveal extensive conservation in the identity of MAE genes between the two species. By analyzing MAE chromatin signature in a large number of cell and tissue types, we show that it remains consistent during terminal cell differentiation and is predominant among cell-type specific genes, suggesting a link between MAE and specification of cell identity. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02215 USA. RP Gimelbrant, AA (reprint author), Dana Farber Canc Inst, Smith SM922B,450 Brookline Ave, Boston, MA 02215 USA. EM gimelbrant@mail.dfci.harvard.edu OI Vigneau, Sebastien/0000-0002-9091-2067 FU National Institutes of Health [R21 CA185000] FX We thank G.-C. Yuan, R. McCole, J. Alvarez, C. Edwards, L. A. Weiss, C. Z. Wang, J. Hutchinson, E. Lundin, and E. Reznichenko for useful discussions. This work was supported in part by the National Institutes of Health (R21 CA185000) and Friends of Dana Farber Cancer Institute. NR 30 TC 8 Z9 8 U1 1 U2 3 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 2160-1836 J9 G3-GENES GENOM GENET JI G3-Genes Genomes Genet. PD AUG 1 PY 2015 VL 5 IS 8 BP 1713 EP 1720 DI 10.1534/g3.115.018853 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA CO6KO UT WOS:000359265800018 PM 26092837 ER PT J AU Iannuzzi, D Kopecky, K Broder-Fingert, S Connors, SL AF Iannuzzi, Dorothea Kopecky, Kimberly Broder-Fingert, Sarabeth Connors, Susan L. TI Addressing the Needs of Individuals with Autism: Role of Hospital-Based Social Workers in Implementation of a Patient-Centered Care Plan SO HEALTH & SOCIAL WORK LA English DT Editorial Material C1 [Iannuzzi, Dorothea] Harvard Vanguard Med Associates Atrius Hlth, Dept Behav Hlth, Concord, MA 01774 USA. [Kopecky, Kimberly] Stanford Med Ctr, Stanford, CA USA. [Broder-Fingert, Sarabeth] Boston Univ, Sch Med, Div Gen Pediat, Boston, MA 02215 USA. [Connors, Susan L.] Massachusetts Gen Hosp, Internal Med & Pediat, Boston, MA 02114 USA. [Connors, Susan L.] Harvard Univ, Lurie Ctr, Sch Med, MGHFC, Boston, MA USA. RP Iannuzzi, D (reprint author), Harvard Vanguard Med Associates Atrius Hlth, Dept Behav Hlth, 330 Baker Ave, Concord, MA 01774 USA. EM diannuzzi222@gmail.com NR 14 TC 0 Z9 0 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0360-7283 EI 1545-6854 J9 HEALTH SOC WORK JI Health Soc. Work PD AUG PY 2015 VL 40 IS 3 BP 245 EP 248 DI 10.1093/hsw/hlv032 PG 4 WC Social Work SC Social Work GA CP2GH UT WOS:000359695000019 PM 26285365 ER PT J AU Khalili, H Chan, AT AF Khalili, Hamed Chan, Andrew T. TI Reply to Comments on Measures of Obesity and Risk of Crohn's Disease and Ulcerative Colitis SO INFLAMMATORY BOWEL DISEASES LA English DT Letter C1 [Khalili, Hamed; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Khalili, Hamed; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. RP Khalili, H (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. FU NIDDK NIH HHS [K23 DK099681] NR 3 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 2015 VL 21 IS 8 BP E18 EP E19 DI 10.1097/MIB.0000000000000485 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CO5HT UT WOS:000359190900007 PM 26111213 ER PT J AU Quiroz, YT Schultz, AP Chen, KW Protas, HD Brickhouse, M Fleisher, AS Langbaum, JB Thiyyagura, P Fagan, AM Shah, AR Muniz, M Arboleda-Velasquez, JF Munoz, C Garcia, G Acosta-Baena, N Giraldo, M Tirado, V Ramirez, DL Tariot, PN Dickerson, BC Sperling, RA Lopera, F Reiman, EM AF Quiroz, Yakeel T. Schultz, Aaron P. Chen, Kewei Protas, Hillary D. Brickhouse, Michael Fleisher, Adam S. Langbaum, Jessica B. Thiyyagura, Pradeep Fagan, Anne M. Shah, Aarti R. Muniz, Martha Arboleda-Velasquez, Joseph F. Munoz, Claudia Garcia, Gloria Acosta-Baena, Natalia Giraldo, Margarita Tirado, Victoria Ramirez, Dora L. Tariot, Pierre N. Dickerson, Bradford C. Sperling, Reisa A. Lopera, Francisco Reiman, Eric M. TI Brain Imaging and Blood Biomarker Abnormalities in Children With Autosomal Dominant Alzheimer Disease A Cross-Sectional Study SO JAMA NEUROLOGY LA English DT Article ID FUNCTIONAL CONNECTIVITY; PRESENILIN-1 MUTATION; GENETIC RISK; ONSET; AGE; ASSOCIATION; CARRIERS; ATROPHY AB IMPORTANCE Brain imaging and fluid biomarkers are characterized in children at risk for autosomal dominant Alzheimer disease (ADAD). OBJECTIVE To characterize and compare structural magnetic resonance imaging (MRI), resting-state and task-dependent functional MRI, and plasma amyloid-beta (A beta) measurements in presenilin 1 (PSEN1) E280A mutation-carrying and noncarrying children with ADAD. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional measures of structural and functional MRI and plasma A beta assays were assessed in 18 PSEN1 E280A carriers and 19 noncarriers aged 9 to 17 years from a Colombian kindred with ADAD. Recruitment and data collection for this study were conducted at the University of Antioquia and the Hospital Pablo Tobon Uribe in Medellin, Colombia, between August 2011 and June 2012. MAIN OUTCOMES AND MEASURES All participants had blood sampling, structural MRI, and functional MRI during associative memory encoding and resting-state and cognitive assessments. Outcome measures included plasma A beta 1-42 concentrations and A beta 1-42: A beta 1-40 ratios, memory encoding-dependent activation changes, resting-state connectivity, and regional gray matter volumes. Structural and functional MRI data were compared using automated brain mapping algorithms and search regions related to AD. RESULTS Similar to findings in adult mutation carriers, in the later preclinical and clinical stages of ADAD, mutation-carrying children were distinguished from control individuals by significantly higher plasma A beta 1-42 levels (mean [SD]: carriers, 18.8 [5.1] pg/mL and noncarriers, 13.1 [3.2] pg/mL; P < .001) and A beta 1-42: A beta 1-40 ratios (mean [SD]: carriers, 0.32 [0.06] and noncarriers, 0.21 [0.03]; P < .001), as well as less memory encoding task-related deactivation in parietal regions (eg, mean [SD] parameter estimates for the right precuneus were -0.590 [0.50] for noncarriers and -0.087 [0.38] for carriers; P < .005 uncorrected). Unlike carriers in the later stages, mutation-carrying children demonstrated increased functional connectivity of the posterior cingulate cortex with medial temporal lobe regions (mean [SD] parameter estimates were 0.038 [0.070] for noncarriers and 0.190 [0.057] for carriers), as well as greater gray matter volumes in temporal regions (eg, left parahippocampus; P < .049, corrected for multiple comparisons). CONCLUSIONS AND RELEVANCE Children at genetic risk for ADAD have functional and structural brain changes and abnormal levels of plasma A beta 1-42. The extent to which the underlying brain changes are either neurodegenerative or developmental remains to be determined. This study provides additional information about the earliest known biomarker changes associated with ADAD. C1 [Quiroz, Yakeel T.; Sperling, Reisa A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Quiroz, Yakeel T.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Quiroz, Yakeel T.; Schultz, Aaron P.; Brickhouse, Michael; Dickerson, Bradford C.; Sperling, Reisa A.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Quiroz, Yakeel T.; Schultz, Aaron P.; Brickhouse, Michael; Dickerson, Bradford C.; Sperling, Reisa A.] Harvard Univ, Sch Med, Boston, MA USA. [Quiroz, Yakeel T.; Munoz, Claudia; Garcia, Gloria; Acosta-Baena, Natalia; Giraldo, Margarita; Tirado, Victoria; Ramirez, Dora L.; Lopera, Francisco] Univ Antioquia, Grp Neurociencias, Medellin, Colombia. [Chen, Kewei; Protas, Hillary D.; Fleisher, Adam S.; Langbaum, Jessica B.; Thiyyagura, Pradeep; Tariot, Pierre N.; Reiman, Eric M.] Banner Alzheimers Inst, Phoenix, AZ USA. [Chen, Kewei; Protas, Hillary D.; Langbaum, Jessica B.; Thiyyagura, Pradeep; Tariot, Pierre N.; Reiman, Eric M.] Alzheimers Consortium, Phoenix, AZ USA. [Chen, Kewei] Arizona State Univ, Dept Math & Stat, Tempe, AZ USA. [Brickhouse, Michael; Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Frontotemporal Dementia Unit, Boston, MA 02114 USA. [Fleisher, Adam S.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Fleisher, Adam S.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Fagan, Anne M.; Shah, Aarti R.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Muniz, Martha] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Arboleda-Velasquez, Joseph F.] Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. [Arboleda-Velasquez, Joseph F.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Tariot, Pierre N.; Reiman, Eric M.] Univ Arizona, Dept Psychiat, Phoenix, AZ USA. [Sperling, Reisa A.] Brigham & Womens Hosp, Dept Neurol, Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. [Reiman, Eric M.] Translat Genom Res Inst, Div Neurogen, Phoenix, AZ USA. RP Quiroz, YT (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,Ste 701, Boston, MA 02114 USA. EM yquiroz@mgh.harvard.edu FU Banner Alzheimer's Foundation; Nomis Foundation; National Institutes of Health Office of the Director [DP5OD019833]; National Institute on Aging [R01 AG031581, P30 AG19610, RF1AG041705, 2UF1 AG032438]; National Eye Institute [EY021624]; Colciencias-Colombia [1115-408-20512, 1115-545- 31651] FX This study was supported by grants from an anonymous foundation (Drs Reiman and Lopera), the Banner Alzheimer's Foundation, the Nomis Foundation, the National Institutes of Health Office of the Director (DP5OD019833 [Dr Quiroz]), the National Institute on Aging (R01 AG031581 [Dr Reiman], P30 AG19610 [Dr Reiman], RF1AG041705 [Drs Reiman, Tariot, and Lopera], and 2UF1 AG032438 [Dr Fagan]), the National Eye Institute (EY021624 [Dr Arboleda-Velasquez]), and Colciencias-Colombia (1115-408-20512 and 1115-545- 31651 [Dr Lopera]). NR 29 TC 13 Z9 14 U1 2 U2 8 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 2015 VL 72 IS 8 BP 912 EP 919 DI 10.1001/jamaneurol.2015.1099 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA CO8GE UT WOS:000359404000012 PM 26121081 ER PT J AU Korvatska, O Leverenz, JB Jayadev, S McMillan, P Kurtz, I Guo, XD Rumbaugh, M Matsushita, M Girirajan, S Dorschner, MO Kiianitsa, K Yu, CE Brkanac, Z Garden, GA Raskind, WH Bird, TD AF Korvatska, Olena Leverenz, James B. Jayadev, Suman McMillan, Pamela Kurtz, Irina Guo, Xindi Rumbaugh, Malia Matsushita, Mark Girirajan, Santhosh Dorschner, Michael O. Kiianitsa, Kostantin Yu, Chang-En Brkanac, Zoran Garden, Gwenn A. Raskind, Wendy H. Bird, Thomas D. TI R47H Variant of TREM2 Associated With Alzheimer Disease in a Large Late-Onset Family Clinical, Genetic, and Neuropathological Study SO JAMA NEUROLOGY LA English DT Article ID FRONTOTEMPORAL DEMENTIA; RISK-FACTOR; PROLIFERATION; MACROPHAGES; ACTIVATION; MUTATIONS; RELATIVES; SPECTRUM; PATHWAY; REVEAL AB IMPORTANCE The R47H variant in the triggering receptor expressed on myeloid cells 2 gene (TREM2), a modulator of the immune response of microglia, is a strong genetic risk factor for Alzheimer disease (AD) and possibly other neurodegenerative disorders. OBJECTIVE To investigate a large family with late-onset AD (LOAD), in which R47H cosegregated with 75% of cases. DESIGN, SETTING, AND PARTICIPANTS This study includes genetic and pathologic studies of families with LOAD from 1985 to 2014. A total of 131 families with LOAD (751 individuals) were included from the University of Washington Alzheimer Disease Research Center. To identify LOAD genes/risk factors in the LOAD123 family with 21 affected members and 12 autopsies, we sequenced 4 exomes. Candidate variants were tested for cosegregation with the disease. TREM2 R47H was genotyped in an additional 130 families with LOAD. We performed clinical and neuropathological assessments of patients with and without R47H and evaluated the variant's effect on brain pathology, cellular morphology, and expression of microglial markers. MAIN OUTCOMES AND MEASURES We assessed the effect of TREM2 genotype on age at onset and disease duration. We compared Braak and Consortium to Establish a Registry for Alzheimer's Disease scores, presence of a-synuclein and TAR DNA-binding protein 43 aggregates, and additional vascular or Parkinson pathology in TREM2 R47H carriers vs noncarriers. Microglial activation was assessed by quantitative immunohistochemistry and morphometry. RESULTS Twelve of 16 patients with AD in the LOAD123 family carried R47H. Eleven patients with dementia had apolipoprotein E 4 (ApoE4) and R47H genotypes. We also found a rare missense variant, D353N, in a nominated AD risk gene, unc-5 homolog C (UNC5C), in5 affected individuals in the LOAD123 family. R47H carriers demonstrated a shortened disease duration (mean [SD], 6.7 [2.8] vs 11.1 [6.6] years; 2-tailed t test; P = .04) and more frequent alpha-synucleinopathy. The panmicroglial marker ionized calcium-binding adapter molecule 1 was decreased in all AD cases and the decrease was most pronounced in R47H carriers (mean [SD], in the hilus: 0.114 [0.13] for R47H_AD vs 0.574 [0.26] for control individuals; 2-tailed t test; P = .005 and vs 0.465 [0.32] for AD; P = .02; in frontal cortex gray matter: 0.006 [0.004] for R47H_AD vs 0.016 [0.01] for AD; P = .04 and vs 0.033 [0.013] for control individuals; P < .001). Major histocompatibility complex class II, a marker of microglial activation, was increased in all patients with AD (AD: 2.5, R47H_AD: 2.7, and control: 1.0; P < .01). CONCLUSIONS AND RELEVANCE Our results demonstrate a complex genetic landscape of LOAD, even in a single pedigree with an apparent autosomal dominant pattern of inheritance. ApoE4, TREM2 R47H, and rare variants in other genes, such as UNC5C D353N, are likely responsible for the notable occurrence of AD in this family. Our findings support the role of the TREM2 receptor in microglial clearance of aggregation-prone proteins that is compromised in R47H carriers and may accelerate the course of disease. C1 [Korvatska, Olena; McMillan, Pamela; Kurtz, Irina; Guo, Xindi; Dorschner, Michael O.; Brkanac, Zoran; Raskind, Wendy H.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA. [Leverenz, James B.] Cleveland Clin Fdn, Lou Ruvo Ctr Brain Hlth, Cleveland, OH 44195 USA. [Jayadev, Suman; Rumbaugh, Malia; Garden, Gwenn A.; Bird, Thomas D.] Univ Washington, Dept Neurol, Seattle, WA 98108 USA. [McMillan, Pamela; Raskind, Wendy H.] Mental Illness Res Educ & Clin Ctr, Dept Vet Affairs, Seattle, WA USA. [Matsushita, Mark; Kiianitsa, Kostantin; Raskind, Wendy H.; Bird, Thomas D.] Univ Washington, Dept Med Med Genet, Seattle, WA 98108 USA. [Girirajan, Santhosh] Penn State Univ, Dept Biochem & Mol Biol, State Coll, PA USA. [Girirajan, Santhosh] Penn State Univ, Dept Anthropol, State Coll, PA USA. [Dorschner, Michael O.; Garden, Gwenn A.] Univ Washington, Dept Pathol, Seattle, WA 98108 USA. [Yu, Chang-En; Bird, Thomas D.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Yu, Chang-En] Univ Washington, Div Gerontol & Geriatr Med, Dept Med, Seattle, WA 98108 USA. RP Bird, TD (reprint author), Univ Washington, Dept Neurol & Med Med Genet, VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, 1660 S ColumbianWay, Seattle, WA 98108 USA. EM tomnroz@uw.edu FU Department of Veterans Affairs (Geriatric Research, Education, and Clinical Centers); National Institutes of Health (National Institute on Aging Genetics Initiative for Late-Onset Alzheimer's Disease) [ADRC P50 AG005136, R01 AG041797-01, R01 NS069719, R01 AG039700, RC1 AG035681]; Van Beber Alzheimer's Disease Research Fund; Washington State Life Sciences Discovery Funds grant [2065508] FX This research was supported by grants from the Department of Veterans Affairs (Geriatric Research, Education, and Clinical Centers); National Institutes of Health grants ADRC P50 AG005136, R01 AG041797-01 (National Institute on Aging Genetics Initiative for Late-Onset Alzheimer's Disease), R01 NS069719, R01 AG039700, and RC1 AG035681; the Van Beber Alzheimer's Disease Research Fund; and Washington State Life Sciences Discovery Funds grant 2065508 to the University of Washington Northwest Institute of Genetic Medicine. NR 38 TC 21 Z9 21 U1 2 U2 8 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 2015 VL 72 IS 8 BP 920 EP 927 DI 10.1001/jamaneurol.2015.0979 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA CO8GE UT WOS:000359404000013 PM 26076170 ER PT J AU Kaup, AR Nettiksimmons, J Yaffe, K AF Kaup, Allison R. Nettiksimmons, Jasmine Yaffe, Kristine TI Diabetes Mellitus and Cognitive Resilience COMMENT & RESPONSE Reply SO JAMA NEUROLOGY LA English DT Letter ID RISK C1 [Kaup, Allison R.] Univ Calif San Francisco, Res Serv, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Kaup, Allison R.; Nettiksimmons, Jasmine; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Epidemiol & Biostat, San Francisco, CA 94121 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. RP Kaup, AR (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco VA Med Ctr, Res Serv, 4150 Clement St,116H, San Francisco, CA 94121 USA. EM allison.kaup@ucsf.edu FU RRD VA [IK2 RX001629] 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 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD AUG PY 2015 VL 72 IS 8 BP 949 EP 950 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA CO8GE UT WOS:000359404000024 PM 26258741 ER PT J AU Subotnik, KL Casaus, LR Ventura, J Luo, JS Hellemann, GS Gretchen-Doorly, D Marder, S Nuechterlein, KH AF Subotnik, Kenneth L. Casaus, Laurie R. Ventura, Joseph Luo, John S. Hellemann, Gerhard S. Gretchen-Doorly, Denise Marder, Stephen Nuechterlein, Keith H. TI Long-Acting Injectable Risperidone for Relapse Prevention and Control of Breakthrough Symptoms After a Recent First Episode of Schizophrenia A Randomized Clinical Trial SO JAMA PSYCHIATRY LA English DT Article ID 1ST-EPISODE SCHIZOPHRENIA; SCHIZOAFFECTIVE DISORDER; MAINTENANCE TREATMENT; ORAL RISPERIDONE; OPEN-LABEL; INJECTION; REMISSION AB IMPORTANCE Long-acting, injectable, second-generation antipsychotic medication has tremendous potential to bring clinical stability to persons with schizophrenia. However, long-acting medications are rarely used following a first episode of schizophrenia. OBJECTIVE To compare the clinical efficacy of the long-acting injectable formulation of risperidone with the oral formulation in the early course of schizophrenia. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial performed at a university-based research clinic, between 2005 and 2012. Eighty-six patients with recent onset of schizophrenia were randomized to receive long-acting injectable risperidone or oral risperidone. Half of each group was simultaneously randomized to receive cognitive remediation to improve cognitive functioning or healthy-behaviors training to improve lifestyle habits and well-being. An intent-to-treat analysis was performed between October 4, 2012, and November 12, 2014. INTERVENTIONS A 12-month trial comparing the long-acting injectable vs oral risperidone and cognitive remediation vs healthy-behaviors training. MAIN OUTCOMES AND MEASURES Psychotic relapse and control of breakthrough psychotic symptoms. RESULTS Of the 86 patients randomized, 3 refused treatment in the long-acting injectable risperidone group. The psychotic exacerbation and/or relapse rate was lower for the long-acting risperidone group compared with the oral group (5% vs 33%; chi(2)(1) = 11.1; P < .001; relative risk reduction, 84.7%). Long-acting injectable risperidone better controlled mean levels of hallucinations and delusions throughout follow-up (beta = -0.30; t(68) = -2.6, P = .01). The cognitive remediation and healthy-behaviors training groups did not differ significantly regarding psychotic relapse, psychotic symptom control, or hospitalization rates, and there were no significant interactions between the 2 medications and the 2 psychosocial treatments. Discontinuations owing to inadequate clinical response were more common in the oral group than in the long-acting risperidone group (chi(2)(1) = 6.1; P = .01). Adherence to oral risperidone did not appear to differ before randomization but was better for the long-acting risperidone group compared with the oral group (t(80) = 5.3; P < .001). Medication adherence was associated with prevention of exacerbation and/or relapse (chi(2)(1) = 11.1; P = .003) and control of breakthrough psychotic symptoms (beta = 0.2; t(79) = 2.1; P = .04). CONCLUSIONS AND RELEVANCE The use of long-acting injectable risperidone after a first episode of schizophrenia has notable advantages for clinical outcomes. The key clinical advantages are apparently owing to the more consistent administration of the long-acting injectable. Such formulations should be offered earlier in the course of illness. C1 [Subotnik, Kenneth L.; Casaus, Laurie R.; Ventura, Joseph; Luo, John S.; Hellemann, Gerhard S.; Gretchen-Doorly, Denise; Marder, Stephen; Nuechterlein, Keith H.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Marder, Stephen] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. [Nuechterlein, Keith H.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. RP Subotnik, KL (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, 300 UCLA Med Plaza,Room 2240, Los Angeles, CA 90095 USA. EM ksubotnik@mednet.ucla.edu FU National Institute of Mental Health [MH037705, MH066286]; Janssen Scientific Affairs, LLC FX This research was supported by grants MH037705 (clinicalTrials.gov Identifier: NCT00333177) and MH066286 (clinicalTrials.gov Identifier: NCT00330551) from the National Institute of Mental Health (Dr Nuechterlein) and supplementary funding and medication was provided by Janssen Scientific Affairs, LLC. NR 23 TC 24 Z9 25 U1 4 U2 9 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 2015 VL 72 IS 8 BP 822 EP 829 DI 10.1001/jamapsychiatry.2015.0270 PG 8 WC Psychiatry SC Psychiatry GA CO5LG UT WOS:000359200000011 PM 26107752 ER PT J AU Tomko, RL Lane, SP Pronove, LM Treloar, HR Brown, WC Solhan, MB Wood, PK Trull, TJ AF Tomko, Rachel L. Lane, Sean P. Pronove, Lisa M. Treloar, Hayley R. Brown, Whitney C. Solhan, Marika B. Wood, Phillip K. Trull, Timothy J. TI Undifferentiated Negative Affect and Impulsivity in Borderline Personality and Depressive Disorders: A Momentary Perspective SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE borderline personality disorder; ecological momentary assessment; emotion differentiation; emotional granularity; impulsivity; depressive disorder ID EMOTION DIFFERENTIATION; AFFECTIVE INSTABILITY; ALCOHOL-USE; AFFECTIVE DYSREGULATION; RETROSPECTIVE RECALL; 4-FACTOR MODEL; EGO DEPLETION; WITHIN-PERSON; SELF-CONTROL; MOOD AB Individuals with borderline personality disorder (BPD) often report experiencing several negative emotions simultaneously, an indicator of "undifferentiated" negative affect. The current study examined the relationship between undifferentiated negative affect and impulsivity. Participants with a current BPD (n = 67) or depressive disorder (DD; n = 38) diagnosis carried an electronic diary for 28 days, reporting on emotions and impulsivity when randomly prompted (up to 6 times per day). Undifferentiated negative affect was quantified using momentary intraclass correlation coefficients, which indicated how consistently negative emotion items were rated across fear, hostility, and sadness subscales. Undifferentiated negative affect at the occasion-level, day-level, and across 28 days was used to predict occasion-level impulsivity. Multilevel modeling was used to test the hypothesis that undifferentiated negative emotion would be a significant predictor of momentary impulsivity above and beyond levels of overall negative affect. Undifferentiated negative affect at the occasion and day levels were significant predictors of occasion-level impulsivity, but undifferentiated negative affect across the 28-day study period was only marginally significant. Results did not differ depending on BPD or DD status, though individuals with BPD did report significantly greater momentary impulsivity and undifferentiated negative affect. Undifferentiated negative affect may increase risk for impulsivity among individuals with BPD and depressive disorders, and the current data suggest that this process can be relatively immediate as well as cumulative over the course of a day. This research supports the consideration of undifferentiated negative affect as a transdiagnostic construct, but one that may be particularly relevant for those with BPD. C1 [Tomko, Rachel L.; Lane, Sean P.; Pronove, Lisa M.; Treloar, Hayley R.; Brown, Whitney C.; Solhan, Marika B.; Wood, Phillip K.; Trull, Timothy J.] Univ Missouri, Columbia, MO 65211 USA. [Tomko, Rachel L.; Lane, Sean P.; Pronove, Lisa M.; Treloar, Hayley R.; Brown, Whitney C.; Solhan, Marika B.; Wood, Phillip K.; Trull, Timothy J.] Midwest Alcoholism Res Ctr, Columbia, MO USA. [Treloar, Hayley R.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Solhan, Marika B.] VA Boston Healthcare Syst, Boston, MA USA. RP Trull, TJ (reprint author), Univ Missouri, Dept Psychol Sci, 210 McAlester Hall, Columbia, MO 65211 USA. EM trullt@missouri.edu OI Treloar Padovano, Hayley/0000-0001-5347-4291 FU National Institutes of Health [R21 MH069472, F31 AA022031, F31 AA021036, P60 AA1198, T32 AA013526] FX Rachel L. Tomko and Sean P. Lane contributed equally to this work. This research was supported by the National Institutes of Health Grants R21 MH069472, F31 AA022031, F31 AA021036, P60 AA1198, and T32 AA013526. NR 73 TC 8 Z9 8 U1 10 U2 17 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 2015 VL 124 IS 3 BP 740 EP 753 DI 10.1037/abn0000064 PG 14 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA CO7YG UT WOS:000359379000023 PM 26147324 ER PT J AU Colvin, M Sweitzer, NK Albert, NM Krishnamani, R Rich, MW Stough, WG Walsh, MN Canary, CAW Allen, LA Bonnell, MR Carson, PE Chan, MC Dickinson, MG Dries, DL Ewald, GA Fang, JC Hernandez, AF Hershberger, RE Katz, SD Moore, S Rodgers, JE Rogers, JG Vest, AR Whellan, DJ Givertz, MM AF Colvin, Monica Sweitzer, Nancy K. Albert, Nancy M. Krishnamani, Rajan Rich, Michael W. Stough, Wendy Gattis Walsh, Mary Norine Canary, Cheryl A. Westlake Allen, Larry A. Bonnell, Mark R. Carson, Peter E. Chan, Michael C. Dickinson, Michael G. Dries, Daniel L. Ewald, Gregory A. Fang, James C. Hernandez, Adrian F. Hershberger, Ray E. Katz, Stuart D. Moore, Stephanie Rodgers, Jo E. Rogers, Joseph G. Vest, Amanda R. Whellan, David J. Givertz, Michael M. TI Heart Failure in Non-Caucasians, Women, and Older Adults: A White Paper on Special Populations From the Heart Failure Society of America Guideline Committee SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Heart failure; women; African American; elderly ID ANGIOTENSIN-CONVERTING-ENZYME; PRESERVED EJECTION FRACTION; QUALITY-OF-LIFE; CARDIAC RESYNCHRONIZATION THERAPY; IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; LEFT-VENTRICULAR DYSFUNCTION; RANDOMIZED INTERVENTION TRIAL; IDIOPATHIC DILATED CARDIOMYOPATHY; GENDER-RELATED DIFFERENCES; ASSOCIATION TASK-FORCE AB The presentation, natural history, clinical outcomes, and response to therapy in patients' with heart failure differ in some ways across populations. Women, older adults, and non-Caucasian racial or ethnic groups compose a substantial proportion of the overall heart failure population, but they have typically been underrepresented in clinical trials. As a result, uncertainty exists about the efficacy of some guideline-directed medical therapies and devices in specific populations, which may result in the under- or overtreatment of these patients. Even when guideline-based treatments are prescribed, socioeconomic, physical, or psychologic factors may affect non-Caucasian and older adult patient groups to a different extent and affect the application, effectiveness, and tolerability of these therapies. Individualized therapy based on tailored biology (genetics, proteomics, metabolomics), socioeconomic and cultural considerations, and individual goals and preferences may be the optimal approach for managing diverse patients. This comprehensive approach to personalized medicine is evolving, but in the interim, the scientific community should continue efforts focused on intensifying research in special populations, prescribing guideline-directed medical therapy unless contraindicated, and implementing evidence-based strategies including patient and family education and multidisciplinary team care in the management of patients. C1 [Colvin, Monica; Sweitzer, Nancy K.] Univ Michigan, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. [Sweitzer, Nancy K.] Univ Arizona, Sarver Heart Ctr, Tucson, AZ USA. [Albert, Nancy M.] Cleveland Clin, Nursing Inst, Cleveland, OH 44106 USA. [Albert, Nancy M.] Cleveland Clin, Inst Heart & Vasc, Cleveland, OH 44106 USA. [Krishnamani, Rajan] Adv Cardiovasc Inst, Middletown, OH USA. [Rich, Michael W.; Ewald, Gregory A.] Washington Univ, Sch Med, St Louis, MO USA. [Stough, Wendy Gattis] Campbell Univ, Coll Pharm & Hlth Sci, Dept Clin Res, Buies Creek, NC 27506 USA. [Walsh, Mary Norine] St Vincent Heart Ctr, Indianapolis, IN USA. [Canary, Cheryl A. Westlake] Azusa Pacific Univ, Sch Nursing, Azusa, CA USA. [Allen, Larry A.] Univ Colorado, Sch Med, Aurora, CO USA. [Bonnell, Mark R.] Univ Toledo, Toledo, OH 43606 USA. [Carson, Peter E.] Georgetown Univ, Washington, DC USA. [Carson, Peter E.] Washington DC Vet Affairs Med Ctr, Washington, DC USA. [Chan, Michael C.] Univ Alberta, Edmonton, AB, Canada. [Dickinson, Michael G.] Spectrum Hlth, Grand Rapids, MI USA. [Dries, Daniel L.] Temple Univ, Sch Med, Temple Heart & Vasc Inst, Philadelphia, PA 19122 USA. [Fang, James C.] Univ Utah, Salt Lake City, UT USA. [Hernandez, Adrian F.; Rogers, Joseph G.] Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27710 USA. [Hershberger, Ray E.] Ohio State Univ, Columbus, OH 43210 USA. [Katz, Stuart D.] NYU, Sch Med, Leon H Charney Div Cardiol, New York, NY USA. [Moore, Stephanie] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rodgers, Jo E.] Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC USA. [Vest, Amanda R.] Tufts Med Ctr, Boston, MA USA. [Whellan, David J.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Med, Philadelphia, PA 19107 USA. [Givertz, Michael M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. RP Givertz, MM (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM mgivertz@partners.org RI Stough, Wendy/R-4287-2016; Hernandez, Adrian F./A-7818-2016; OI Stough, Wendy/0000-0001-8290-1205; Hernandez, Adrian F./0000-0003-3387-9616; Stuart, Katz/0000-0003-2340-2021 FU Acorda; Otsuka; National Institutes of Health; National Heart, Lung, and Blood Institute; Patient Centered Outcomes Research Institute; Palatin Technologies; Thoratec; Biocontrol; Novartis; Shape Systems; St. Jude Medical; Amgen; Astra-Zeneca; Boston Scientific; Bristol-Myers Squibb; Glaxo-Smith-Kline; Janssen; Medtronic; Portola Pharmaceuticals; Forest; Merck; ResMed; Pozon FX Monica Colvin: None. Nancy K. Sweitzer: research grants/fellowship support (Novartis, Acorda). Nancy M. Albert: consultant/advisory board (Novartis, Amgen, Medtronic). Rajan Krishnamani: site principal investigator for the TRUE-AHF trial. Michael W. Rich: None. Wendy Gattis Stough: consultant (Relypsa, Covis Pharmaceuticals). Mary Norine Walsh: None. Cheryl A. Westlake Canary: None. Larry A. Allen: consultant/advisory board (Novartis, Johnson and Johnson, Janssen); research grants/fellowship support (Otsuka; National Institutes of Health; National Heart, Lung, and Blood Institute; Patient Centered Outcomes Research Institute). Mark R. Bonnell: None. Peter E. Carson: consultant/advisory board (Novartis, St. Jude, Takeda). Michael C. Chan: consultant/advisory board (Servier, Novartis). Michael G. Dickinson: honoraria/speakers bureau (Thoratec, Medtronic). Daniel L. Dries: research grants/fellowship support (Palatin Technologies). Gregory A. Ewald: honoraria/speakers bureau (Thoratec, Heart Ware); research grants/fellowship support (Thoratec, Biocontrol, Novartis, Shape Systems, St. Jude Medical). James C. Fang: consultant/advisory board: Abiomed. Adrian F. Hernandez: honoraria/speakers bureau (Amgen, Bristol-Myers Squibb, Gilead, Janssen, Novartis, Pluristem, Sensible, Myokardia); consultant/advisory board (Amgen, Bristol-Myers Squibb, Gilead, Janssen, Novartis, Pluristem, Sensible, Myokardia); research grants/fellowship support (Amgen, Astra-Zeneca, Boston Scientific, Bristol-Myers Squibb, Glaxo-Smith-Kline, Janssen, Medtronic, Portola Pharmaceuticals). Ray E. Hershberger: None. Stuart D. Katz: honoraria/speakers bureau (Amgen, Otsuka); consultant/advisory board (Bristol-Myers Squibb, Janssen, Merck, Luitpold, Amgen). Stephanie Moore: None. Jo E. Rodgers: consultant/advisory board (Amgen, Novartis). Joseph G. Rogers: None. Amanda R. Vest: None. David J. Whellan: consultant/advisory board. (Clinalogix); research grants/fellowship support (Medtronic, Forest, Merck, ResMed, Pozon). Michael M. Givertz: consultant/advisory board (Merck, Cardioxyl, Janssen). NR 220 TC 8 Z9 8 U1 5 U2 15 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 EI 1532-8414 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2015 VL 21 IS 8 BP 674 EP 693 DI 10.1016/j.cardfail.2015.05.013 PG 20 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CO8CG UT WOS:000359392000011 PM 26051012 ER PT J AU Niehaus, ED Malhotra, R Cocca-Spofford, D Semigran, M Lewis, GD AF Niehaus, Emily D. Malhotra, Rajeev Cocca-Spofford, Diane Semigran, Marc Lewis, Gregory D. TI Repletion of Iron Stores With the Use of Oral Iron Supplementation in Patients With Systolic Heart Failure SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Heart failure; iron deficiency; anemia; iron supplementation ID INTRAVENOUS IRON; FERRIC CARBOXYMALTOSE; EXERCISE CAPACITY; DEFICIENCY; ANEMIA; HEPCIDIN; THERAPY; TRIAL; HF AB Background: Iron deficiency is associated with reduced functional capacity and increased mortality in patients with heart failure with reduced ejection fraction (HFrEF). Correction of iron deficiency in HFrEF patients with the use of intravenous iron improves symptoms, quality of life, and exercise performance. Whether oral iron improves iron stores in HFrEF patients is unknown. We conducted a retrospective study to assess the efficacy of oral iron supplementation in iron-deficient HFrEF patients. Methods and Results: Iron-deficient HFrEF patients with a record of oral iron supplementation and iron studies before and similar to 180 days after supplementation were identified. Iron deficiency was defined as ferritin <100 ng/mL or as ferritin 100-300 ng/mL with transferrin saturation (Tsat) <20%. Spearman correlation was performed to assess for treatment responsiveness. In 105 patients, ferritin (from median 39 ng/mL to 75 ng/mL), Tsat (from 10% to 21%), iron (from 34 mu g/dL to 69 mu g/dL), and hemoglobin (from 10.4 g/dL to 11.6 g/dL) values increased (P < .0001), whereas total iron-binding capacity decreased (from 343 to 313 mu g/dL; P = .0007) at 164 days after initiation of oral iron supplementation. Conclusions: In this retrospective study, oral iron supplementation improved iron stores similarly to previously reported results with the use of intravenous iron repletion in HFrEF patients, suggesting that oral iron merits prospective evaluation as an intervention strategy in HFrEF. C1 [Niehaus, Emily D.; Malhotra, Rajeev; Cocca-Spofford, Diane; Semigran, Marc; Lewis, Gregory D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Lewis, GD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Cardiol,Med, 55 Fruit St,GRB 8, Boston, MA 02114 USA. EM glewis@partners.org OI Malhotra, Rajeev/0000-0003-0120-4630 FU Hassenfeld Clinical Scholars Program; NIH [U10HL110337] FX This study was funded by the Hassenfeld Clinical Scholars Program and NIH U10HL110337. NR 16 TC 3 Z9 3 U1 1 U2 4 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 EI 1532-8414 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2015 VL 21 IS 8 BP 694 EP 697 DI 10.1016/j.cardfail.2015.05.006 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CO8CG UT WOS:000359392000012 PM 26028263 ER PT J AU Lewis, GD Dress, A Ewald, GA Flanagan, J Eckman, P Eisman, A Nelson, J MacCarter, D Kocheril, A AF Lewis, Gregory D. Dress, Ashley Ewald, Gregory A. Flanagan, Jean Eckman, Peter Eisman, Aaron Nelson, Jennifer MacCarter, Dean Kocheril, Abraham TI Pre-discharge Bedside Exercise Gas Exchange Measurements Predict 30 Day Heart Failure Patient Readmissions SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 19th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 26-29, 2015 CL National Harbor, MD SP Heart Failure Soc Amer C1 [Lewis, Gregory D.; Dress, Ashley; Eisman, Aaron] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ewald, Gregory A.; Flanagan, Jean] Washington Univ, St Louis, MO USA. [Eckman, Peter; Nelson, Jennifer] Univ Minnesota, Minneapolis, MN USA. [MacCarter, Dean] Shape Med Syst, St Paul, MN USA. [Kocheril, Abraham] Univ Illinois, Champaign, IL 61820 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 EI 1532-8414 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2015 VL 21 IS 8 SU S MA 314 BP S126 EP S126 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CO8CI UT WOS:000359392200318 ER PT J AU Nagatomo, Y McNamara, DM Alexis, JD Cooper, LT Dec, GW Pauly, DF Sheppard, R Starling, RC Tang, WHW AF Nagatomo, Yuji McNamara, Dennis M. Alexis, Jeffrey D. Cooper, Leslie T. Dec, G. William Pauly, Daniel F. Sheppard, Richard Starling, Randall C. Tang, W. H. Wilson TI The Presence of IgG3 Autoantibody Against beta 1 Adrenergic Receptors is Associated with Favorable Myocardial Recovery in Patients with Recent Onset Cardiomyopathy - a Post-hoc Analysis of IMAC-2 Study SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 19th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 26-29, 2015 CL National Harbor, MD SP Heart Failure Soc Amer C1 [Nagatomo, Yuji; Starling, Randall C.; Tang, W. H. Wilson] Cleveland Clin, Cleveland, OH 44106 USA. [McNamara, Dennis M.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Alexis, Jeffrey D.] Univ Rochester, Med Ctr, Sch Med & Dent, Rochester, NY 14642 USA. [Cooper, Leslie T.] Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. [Dec, G. William] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pauly, Daniel F.] Univ Missouri, Truman Med Ctr, Kansas City, MO 64108 USA. [Sheppard, Richard] McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 EI 1532-8414 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2015 VL 21 IS 8 SU S MA 040 BP S27 EP S28 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CO8CI UT WOS:000359392200065 ER PT J AU Psotka, MA Teerlink, JR Chiswell, K Cleland, JG Cotter, G Davison, BA Givertz, MM Metra, M Ponikowski, P Voors, AA Bloomfield, DM O'Connor, CM AF Psotka, Mitchell A. Teerlink, John R. Chiswell, Karen Cleland, John G. Cotter, Gad Davison, Beth A. Givertz, Michael M. Metra, Marco Ponikowski, Piotr Voors, Adriaan A. Bloomfield, Daniel M. O'Connor, Christopher M. TI Prediction of Post-Discharge Outcomes for Patients Hospitalized with Heart Failure: Results from PROTECT SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 19th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 26-29, 2015 CL National Harbor, MD SP Heart Failure Soc Amer C1 [Psotka, Mitchell A.; Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Psotka, Mitchell A.; Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. [Chiswell, Karen; O'Connor, Christopher M.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Cleland, John G.] Univ London Imperial Coll Sci Technol & Med, Royal Brompton Hosp, Natl Heart & Lung Inst, London, England. [Cleland, John G.] Univ London Imperial Coll Sci Technol & Med, Harefield Hosp, Natl Heart & Lung Inst, London, England. [Cotter, Gad; Davison, Beth A.] Momentum Res, Durham, NC USA. [Givertz, Michael M.] Brigham & Womens Hosp, Boson, MA USA. [Metra, Marco] Univ Brescia, Brescia, Italy. [Ponikowski, Piotr] Med Univ, Clin Mil Hosp, Wroclaw, Poland. [Voors, Adriaan A.] Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Bloomfield, Daniel M.] Merck Res Labs, Rahway, NJ USA. RI Ponikowski, Piotr/O-6454-2015 OI Ponikowski, Piotr/0000-0002-3391-7064 NR 0 TC 0 Z9 0 U1 0 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 EI 1532-8414 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2015 VL 21 IS 8 SU S MA 135 BP S64 EP S64 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CO8CI UT WOS:000359392200160 ER PT J AU O'Brien, SE Schrodi, SJ Ye, Z Brilliant, MH Virani, SS Brautbar, A AF O'Brien, Sarah E. Schrodi, Steven J. Ye, Zhan Brilliant, Murray H. Virani, Salim S. Brautbar, Ariel TI Differential Lipid Response to Statins Is Associated With Variants in the BUD13-APOA5 Gene Region SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Article ID GENOME-WIDE ASSOCIATION; FENOFIBRIC ACID; WHOLE-GENOME; THERAPY; EFFICACY; COHORT; TRIAL; TOOL AB Genetic variants within the BUD13-APOA5 gene region are known to be associated with high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels. Recent studies suggest that single nucleotide polymorphisms (SNPs) within this region affect HDL-C response to statin-fibrate combination therapy and low-density lipoprotein cholesterol (LDL-C) response to statin therapy. We hypothesized that SNPs within the BUD13-APOA5 region are associated with TG, HDL-C, and LDL-C response to statin therapy. We examined 1520 observations for 1086 patients from the Personalized Medicine Research Project, a large biorepository at the Marshfield Clinic Research Foundation, who had received statin therapy and been previously genotyped for polymorphisms in the 11q23 chromosomal region. A significant differential response to statin therapy was observed for 3 SNPs. The minor allele at rs11605293 significantly attenuated TG-lowering response to pravastatin (P = 0.000159), whereas the minor allele at rs12806755 was associated with a similar response to lovastatin (P = 0.000192). Genotypes at rs947990 significantly attenuated LDL-C reduction to atorvastatin therapy (P = 0.000668) with some patients with the minor allele having LDL-C increase after therapy. No SNPs within the BUD13-APOA5 region were associated with a significant effect on HDL-C reduction in response to statin therapy. In conclusion, this study suggests that common SNPs within the BUD13-APOA5 can affect TG and LDL-C response to statin therapy in a North American population. C1 [O'Brien, Sarah E.; Schrodi, Steven J.; Ye, Zhan; Brilliant, Murray H.; Brautbar, Ariel] Marshfield Clin Res Fdn, Ctr Human Genet, Marshfield, WI USA. [Virani, Salim S.] Baylor Coll Med, Hlth Serv Res & Dev, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Virani, Salim S.] Baylor Coll Med, Dept Med, Sect Cardiovasc Res, Houston, TX 77030 USA. [Brautbar, Ariel] Cook Childrens Med Ctr, Div Genet & Endocrinol, Ft Worth, TX USA. RP Brautbar, A (reprint author), Baylor Coll Med, Dept Med, 6565 Fannin St, Houston, TX 77030 USA. EM brautbar@bcm.edu OI Schrodi, Steven/0000-0003-2304-8528; Virani, Salim/0000-0001-9541-6954 FU Marshfield Clinic Research Foundation; Clinical and Translational Science Award (CTSA) program through the National Center for Research Resources (NCRR) [1UL1RR025011]; National Center for Advancing Translational Sciences (NCATS) [9U54TR000021]; NCATS [UL1TR000427] FX Supported by Marshfield Clinic Research Foundation, generous donors to Marshfield Clinic, and the Clinical and Translational Science Award (CTSA) program, previously through the National Center for Research Resources (NCRR) grant 1UL1RR025011 and the National Center for Advancing Translational Sciences (NCATS) grant 9U54TR000021, and now by the NCATS grant UL1TR000427. NR 21 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0160-2446 EI 1533-4023 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD AUG PY 2015 VL 66 IS 2 BP 183 EP 188 DI 10.1097/FJC.0000000000000261 PG 6 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA CP1WO UT WOS:000359668300008 PM 25900265 ER PT J AU Rivlin, M Fei, W Mudgal, CS AF Rivlin, Michael Fei, Wu Mudgal, Chaitanya S. TI Bennett Fracture SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Editorial Material ID OPEN REDUCTION; FIXATION C1 [Rivlin, Michael] Thomas Jefferson Univ, Rothman Inst, Philadelphia, PA 19107 USA. [Fei, Wu] Wuhan Univ, Renmin Hosp, Dept Orthoped Surg, Wuhan 430072, Hubei Province, Peoples R China. [Mudgal, Chaitanya S.] Harvard Univ, Massachusetts Gen Hosp, Dept Hand Surg, Boston, MA 02114 USA. RP Mudgal, CS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Hand Surg, 55 Fruit St, Boston, MA 02114 USA. EM cmudgal@partners.org OI Rivlin, Michael/0000-0003-1290-3410 NR 12 TC 0 Z9 0 U1 1 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 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD AUG PY 2015 VL 40 IS 8 BP 1667 EP 1668 DI 10.1016/j.jhsa.2015.05.017 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CO9QS UT WOS:000359511100022 PM 26143965 ER PT J AU Heidari, P Esfahani, SA Turker, NS Wong, G Wang, TC Rustgi, AK Mahmood, U AF Heidari, Pedram Esfahani, Shadi A. Turker, Nazife S. Wong, Gabrielle Wang, Timothy C. Rustgi, Anil K. Mahmood, Umar TI Imaging of Secreted Extracellular Periostin, an Important Marker of Invasion in the Tumor Microenvironment in Esophageal Cancer SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE periostin; immuno-PET imaging; extracellular matrix; tumor microenvironment; esophageal cancer ID CELL-ADHESION MOLECULE; PROGNOSTIC MARKER; GROWTH; EXPRESSION; BREAST; ANGIOGENESIS; P120-CATENIN; METASTASIS; MICE AB Periostin, an extracellular matrix protein, plays key role in cell adhesion and motility within the tumor microenvironment and is correlated with tumor invasion. We developed and characterized a PET tracer that specifically targets periostin and evaluated the probe in preclinical models of esophageal squamous cell carcinoma (ESCC). Methods: The Institutional Animal Care and Use Committee approved all animal studies. Antiperiostin-F(ab')(2) was generated from a monoclonal antibody by enzymatic digestion, conjugated to DOTA, and labeled with Cu-64. Human ESCC cell lines, TE-11 with high and TT with minimal periostin expression, were implanted in nu/nu mice to generate the positive and control tumor models, respectively. PET/CT imaging was performed at 6, 12, and 24 h and organ-specific biodistribution at 24 h after probe injection. Additionally the probe was tested in a genetically engineered mouse model of periostin-expressing distal esophageal/forestomach ESCC. Tissue microarrays of esophageal neoplasms and ESCC as well as extracted tumor samples were stained for periostin. Results: We generated a Cu-64-DOTA-antiperiostin-F(ab')(2) with a dissociation constant of 29.2 +/- 3.0 nM. PET/CT images and biodistribution studies showed significantly higher tracer uptake in TE-11 than TT tumors (maximum standardized uptake value, 24 h: 0.67 +/- 0.09 vs. 0.36 +/- 0.03, P < 0.0005; percentage injected dose per gram, 24 h: 3.24 +/- 0.65 vs. 1.63 +/- 0.49, P < 0.0001). In genetically engineered mouse models, ESCC high periostin tracer uptake anatomically correlated with the F-18-FDG uptake at the gastroesophageal junction. All of the ESCC cores and 96.2% of adenocarcinoma stained positive for periostin, with most stained strongly (67.3% and 69.3%, respectively). Conclusion: We demonstrated that specific imaging of extracellular matrix periostin in ESCC is feasible using a targeted PET tracer. Detection of periostin in the tumor microenvironment may help with early detection, postsurgical follow-up, and in situ characterization of primary and metastatic lesions. C1 [Heidari, Pedram; Esfahani, Shadi A.; Turker, Nazife S.; Mahmood, Umar] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Wong, Gabrielle; Rustgi, Anil K.] Columbia Univ, Dept Med, Med Ctr, Div Digest & Liver Dis, New York, NY USA. [Wang, Timothy C.] Univ Penn, Dept Med, Perebnan Sch Med, Div Gastroenterol, Philadelphia, PA 19104 USA. RP Mahmood, U (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. EM umahmood@mgh.harvard.edu FU NCI NIH HHS [U01CA084301, P50 CA127003, P50CA127003, R01 CA166582, U01 CA084301, U01 CA143056] NR 22 TC 1 Z9 1 U1 0 U2 3 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 PY 2015 VL 56 IS 8 BP 1246 EP 1251 DI 10.2967/jnumed.115.156216 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CO5CX UT WOS:000359178300036 PM 26069303 ER PT J AU El Ouaamari, A Zhou, JY Liew, CW Shirakawa, J Dirice, E Gedeon, N Kahrarnan, S De Jesus, DF Bhatt, S Kim, JS Clauss, TRW Camp, DG Smith, RD Qian, WJ Kulkarni, RN AF El Ouaamari, Abdelfattah Zhou, Jian-Ying Liew, Chong Wee Shirakawa, Jun Dirice, Ercument Gedeon, Nicholas Kahrarnan, Sevim De Jesus, Dario F. Bhatt, Shweta Kim, Jong-Seo Clauss, Therese R. W. Camp, David G., II Smith, Richard D. Qian, Wei-Jun Kulkarni, Rohit N. TI Compensatory Islet Response to Insulin Resistance Revealed by Quantitative Proteomics SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE Insulin resistance; pancreatic islets; proteome; proliferation; metabolism; function ID BETA-CELL DYSFUNCTION; MASS-SPECTROMETRY; INDUCED OBESITY; ANTIBODY-FREE; MICE; SECRETION; GROWTH; PROTEINS; PROLIFERATION; ADAPTATION AB Compensatory islet response is a distinct feature of the prediabetic insulin-resistant state in humans and rodents. To identify alterations in the islet proteome that characterize the adaptive response, we analyzed islets from 5 month old male control, high-fat diet fed (HFD), or obese ob/ob mice by LC-MS/MS and quantified similar to 1100 islet proteins (at least two peptides) with a false discovery rate < 1%. Significant alterations in abundance were observed for similar to 350 proteins among groups. The majority of alterations were common to both models, and the changes of a subset of similar to 40 proteins and 12 proteins were verified by targeted quantification using selected reaction monitoring and western blots, respectively. The insulin-resistant islets in both groups exhibited reduced expression of proteins controlling energy metabolism, oxidative phosphorylation, hormone processing, and secretory pathways. Conversely, an increased expression of molecules involved in protein synthesis and folding suggested effects in endoplasmic reticulum stress response, cell survival, and proliferation in both insulin-resistant models. In summary, we report a unique comparison of the islet proteome that is focused on the compensatory response in two insulin-resistant rodent models that are not overtly diabetic. These data provide a valuable resource of candidate proteins to the scientific community to undertake further studies aimed at enhancing beta-cell mass in patients with diabetes. The data are available via the MassIVE repository, under accession no. MSV000079093. C1 [El Ouaamari, Abdelfattah; Shirakawa, Jun; Dirice, Ercument; Gedeon, Nicholas; Kahrarnan, Sevim; De Jesus, Dario F.; Bhatt, Shweta; Kulkarni, Rohit N.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Islet Cell & Regenerat Biol,Joslin Diabet Ctr, Boston, MA 02215 USA. [Zhou, Jian-Ying; Kim, Jong-Seo; Clauss, Therese R. W.; Camp, David G., II; Smith, Richard D.; Qian, Wei-Jun] Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA. [Zhou, Jian-Ying; Kim, Jong-Seo; Clauss, Therese R. W.; Camp, David G., II; Smith, Richard D.; Qian, Wei-Jun] Pacific NW Natl Lab, Environm Mol Sci Lab, Richland, WA 99352 USA. [Liew, Chong Wee] Univ Illinois, Dept Physiol & Biophys, Chicago, IL 60612 USA. RP Qian, WJ (reprint author), Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA. EM weijun.qian@pnnl.gov; rohit.kulkarni@joslin.harvard.edu RI Smith, Richard/J-3664-2012; Dirice, Ercument/B-2825-2017; OI Smith, Richard/0000-0002-2381-2349; Kahraman, Sevim/0000-0002-2880-6589; Shirakawa, Jun/0000-0002-0822-8750 FU NIH [R01 DK074795, R01 DK067536, R01 DK103215, K99 DK090210]; Societe Francophone du Diabete; Association Francaise des Diabetiques; American Diabetes Association; JDRF advanced postdoctoral fellowship; DOE [DE-AC05-76RLO-1830] FX This work was supported by NIH grant nos. R01 DK074795, R01 DK067536, R01 DK103215, and K99 DK090210, Societe Francophone du Diabete (to A.E.), Association Francaise des Diabetiques (to A.E.), American Diabetes Association (to A.E.), and JDRF advanced postdoctoral fellowship (to A.E.). Samples were analyzed using capabilities developed under the support of the NIH Biomedical Technology Research Resource for integrative biology (P41 GM103493). Significant portions of the work were performed in the Environmental Molecular Science Laboratory, a DOE/BER national scientific user facility at Pacific Northwest National Laboratory (PNNL) in Richland, Washington. PNNL is operated for the DOE by Battelle under contract no. DE-AC05-76RLO-1830. NR 72 TC 3 Z9 3 U1 4 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 EI 1535-3907 J9 J PROTEOME RES JI J. Proteome Res. PD AUG PY 2015 VL 14 IS 8 BP 3111 EP 3122 DI 10.1021/acs.jproteome.5b00587 PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CO8DA UT WOS:000359394000009 PM 26151086 ER PT J AU Lipsky, RK McGuinness, TM AF Lipsky, Rachele K. McGuinness, Teena M. TI Binge Eating Disorder and Youth SO JOURNAL OF PSYCHOSOCIAL NURSING AND MENTAL HEALTH SERVICES LA English DT Article ID ADOLESCENT GIRLS; COMORBIDITY; CHILDREN; OBESITY; ADULTS; TRIAL AB Children and adolescents who eat unusually large amounts of food, feel guilty about it, and try to hide their overeating may be struggling with binge eating disorder (BED), a condition associated with suicidal ideation and other eating disorders. Although BED is new to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, the syndrome is becoming increasingly recognized. The study of BED in children and adolescents is in its natal phase, but the importance of recognition and possible treatment strategies are discussed in the current article along with psychiatric nursing implications. C1 [Lipsky, Rachele K.] Birmingham VA Med Ctr, Birmingham, AL 35233 USA. [McGuinness, Teena M.] Univ Alabama Birmingham, Sch Nursing, Birmingham, AL USA. RP Lipsky, RK (reprint author), Birmingham VA Med Ctr, 700 South 19th St, Birmingham, AL 35233 USA. EM Rachele.Lipsky@va.gov NR 19 TC 1 Z9 1 U1 2 U2 6 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0279-3695 EI 1938-2413 J9 J PSYCHOSOC NURS MEN JI J. Psychosoc. Nurs. Ment. Health Serv. PD AUG PY 2015 VL 53 IS 8 BP 18 EP 22 DI 10.3928/02793695-20150720-03 PG 5 WC Nursing SC Nursing GA CO6YD UT WOS:000359302800009 PM 26268477 ER PT J AU McCauley, HL Silverman, JG Decker, MR Agenor, M Borrero, S Tancredi, DJ Zelazny, S Miller, E AF McCauley, Heather L. Silverman, Jay G. Decker, Michele R. Agenor, Madina Borrero, Sonya Tancredi, Daniel J. Zelazny, Sarah Miller, Elizabeth TI Sexual and Reproductive Health Indicators and Intimate Partner Violence Victimization Among Female Family Planning Clinic Patients Who Have Sex with Women and Men SO JOURNAL OF WOMENS HEALTH LA English DT Article ID ADOLESCENT FEMALES; UNINTENDED PREGNANCY; HETEROSEXUAL WOMEN; BISEXUAL WOMEN; UNITED-STATES; YOUNG-WOMEN; ABUSE; RISK; ORIENTATION; DISPARITIES AB Background: Sexual minority women are more likely than heterosexual women to have ever experienced intimate partner violence (IPV). Although IPV is associated with sexual risk and poor reproductive health outcomes among US women overall, little is known about whether IPV is related to sexual and reproductive health indicators among sexual minority women in particular. Methods: Baseline data from a prospective intervention trial were collected from women ages 16-29 years at 24 family planning clinics in western PA (n=3,455). Multivariable logistic regression for clustered survey data was used to compare women who have sex with men only (WSM) and women who have sex with women and men (WSWM) on (1) IPV prevalence and (2) sexual and reproductive health behaviors, outcomes, and services use, controlling for IPV. Finally, we tested the interaction of sexual minority status and IPV. Results: WSWM were significantly more likely than WSM to report a lifetime history of IPV (adjusted odds ratio (AOR): 3.00; 95% confidence interval (CI): 2.30, 3.09). Controlling for IPV, WSWM reported higher levels of sexual risk behaviors (e.g., unprotected vaginal and anal sex), male-perpetrated reproductive coercion, unwanted pregnancy, and sexually transmitted infection (STI) and pregnancy testing but less contraceptive care seeking. The association between IPV and lifetime STI diagnosis was greater among WSWM than among WSM. Conclusions: IPV was pervasive and associated with sexual risk and reproductive health indicators among WSWM in this clinic-based setting. Healthcare providers' sexual risk assessment and provision of sexual and reproductive health services should be informed by an understanding of women's sexual histories, including sex of sexual partners and IPV history, in order to help ensure that all women receive the clinical care they need. C1 [McCauley, Heather L.; Zelazny, Sarah; Miller, Elizabeth] Univ Pittsburgh, UPMC, Dept Pediat,Childrens Hosp Pittsburgh, Div Adolescent & Young Adult Med,Sch Med, Pittsburgh, PA 15261 USA. [Silverman, Jay G.] Univ Calif San Diego, Div Global Publ Hlth, Sch Med, La Jolla, CA 92093 USA. [Decker, Michele R.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Populat Family & Reprod Hlth, Baltimore, MD USA. [Agenor, Madina] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Agenor, Madina] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Borrero, Sonya] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Borrero, Sonya] VA Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Tancredi, Daniel J.] Univ Calif Davis, Sch Med, Dept Pediat, Sacramento, CA 95817 USA. RP McCauley, HL (reprint author), UPMC, Div Adolescent Med, Childrens Hosp Pittsburgh, 3414 Fifth Ave,CHOB Room 109, Pittsburgh, PA 15213 USA. EM heather.mccauley@chp.edu OI Tancredi, Daniel/0000-0002-3884-7907 FU NIH/ORWH Building Interdisciplinary Research Careers in Women's Health (BIRCWH) [K12HD043441]; National Institute of Child Health and Human Development [R01HD064407] FX This study was supported by NIH/ORWH Building Interdisciplinary Research Careers in Women's Health (BIRCWH) K12HD043441 scholar funds to Heather McCauley. Funding for this study is from the National Institute of Child Health and Human Development (R01HD064407) to Elizabeth Miller and Jay Silverman. NR 44 TC 5 Z9 5 U1 1 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD AUG 1 PY 2015 VL 24 IS 8 BP 621 EP 628 DI 10.1089/jwh.2014.5032 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA CP1FL UT WOS:000359621600002 PM 25961855 ER PT J AU Knight, SJ Mohamed, AF Marshall, DA Ladabaum, U Phillips, KA Walsh, JME AF Knight, Sara J. Mohamed, Ateesha F. Marshall, Deborah A. Ladabaum, Uri Phillips, Kathryn A. Walsh, Judith M. E. TI Value of Genetic Testing for Hereditary Colorectal Cancer in a Probability-Based US Online Sample SO MEDICAL DECISION MAKING LA English DT Article DE genetics; oncology; internal medicine; discrete choice; utility assessment ID LYNCH-SYNDROME; PRIMARY-CARE; CHOICE EXPERIMENTS; CONJOINT-ANALYSIS; PATIENT PREFERENCES; EXPERIMENTAL-DESIGN; GENERAL-POPULATION; COST-EFFECTIVENESS; FAMILY-HISTORY; KNOWLEDGE AB Background. While choices about genetic testing are increasingly common for patients and families, and public opinion surveys suggest public interest in genomics, it is not known how adults from the general population value genetic testing for heritable conditions. We sought to understand in a US sample the relative value of the characteristics of genetic tests to identify risk of hereditary colorectal cancer, among the first genomic applications with evidence to support its translation to clinical settings. Methods. A Web-enabled choice-format conjoint survey was conducted with adults age 50 years and older from a probability-based US panel. Participants were asked to make a series of choices between 2 hypothetical blood tests that differed in risk of false-negative test, privacy, and cost. Random parameters logit models were used to estimate preferences, the dollar value of genetic information, and intent to have genetic testing. Results. A total of 355 individuals completed choice-format questions. Cost and privacy were more highly valued than reducing the chance of a false-negative result. Most (97% [95% confidence interval (CI)], 95%-99%) would have genetic testing to reduce the risk of dying of colorectal cancer in the best scenario (no false negatives, results disclosed to primary care physician). Only 41% (95% CI, 25%-57%) would have genetic testing in the worst case (20% false negatives, results disclosed to insurance company). Conclusions. Given the characteristics and levels included in the choice, if false-negative test results are unlikely and results are shared with a primary care physician, the majority would have genetic testing. As genomic services become widely available, primary care professionals will need to be increasingly knowledgeable about genetic testing decisions. C1 [Knight, Sara J.] Birmingham Vet Affairs Med Ctr, Hlth Serv Res & Dev Program, Birmingham, AL USA. [Knight, Sara J.] Univ Alabama Birmingham, Div Prevent Med, Dept Med, Birmingham, AL 35205 USA. [Mohamed, Ateesha F.] Bayer Healthcare Pharmaceut Inc, Specialty Med, CHEOR, Whippany, NJ USA. [Marshall, Deborah A.] Univ Calgary, Dept Community Hlth Sci, Calgary, AB, Canada. [Ladabaum, Uri] Stanford Univ, Dept Med, Palo Alto, CA 94304 USA. [Phillips, Kathryn A.] Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94143 USA. [Phillips, Kathryn A.] Univ Calif San Francisco, Inst Hlth Policy Studies, San Francisco, CA 94143 USA. [Walsh, Judith M. E.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Walsh, Judith M. E.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Walsh, Judith M. E.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. RP Knight, SJ (reprint author), Univ Alabama Birmingham, Div Prevent Med, Med Towers Bldg,1717 11th Ave South,Suite 650, Birmingham, AL 35205 USA. EM sjknight@uab.edu FU National Cancer Institute [P01CA130818-1A1] FX Received 21 April 2013 from Health Services Research and Development Program, Birmingham Veterans Affairs Medical Center, Birmingham, Alabama, USA (SJK); Division of Preventive Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA (SJK); CHEOR, Specialty Medicine, Bayer Healthcare Pharmaceuticals, Inc., Whippany, New Jersey, USA (AFM); Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada (DAM); Department of Medicine, Stanford University, Palo Alto, California, USA (UL); Department of Clinical Pharmacy and Institute for Health Policy Studies, University of California at San Francisco, San Francisco, California, USA (KAP); and Departments of Medicine and Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, California, USA (JMEW). Uri Ladabaum, MD, MS, declares a potential perceived conflict of interest with Exact Sciences Corporation (Madison, WI) and Given Imaging Ltd. (Duluth, GA)/Covidien Plc (Dublin, Ireland), for whom he has served as consultant, and Mauna Kea Technologies, Inc. (Suwanee, GA), for whom he has served on an advisory board. This work was supported with a grant from the National Cancer Institute (P01CA130818-1A1) (Kathryn A. Phillips, principal investigator; Judith M. E. Walsh and Sara J. Knight, co-leaders of the Preferences Project). This article represents the perspective of the authors and does not necessarily represent the views of the Department of Veterans Affairs or the US government. The funding agreement ensured the authors' independence in designing the study, interpreting the data, and writing and publishing the report. Revision accepted for publication 11 November 2014. NR 56 TC 0 Z9 0 U1 3 U2 13 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X EI 1552-681X J9 MED DECIS MAKING JI Med. Decis. Mak. PD AUG PY 2015 VL 35 IS 6 BP 734 EP 744 DI 10.1177/0272989X14565820 PG 11 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA CO8NX UT WOS:000359427600007 ER PT J AU Muhlberger, N Kurzthaler, C Iskandar, R Krahn, MD Bremner, KE Oberaigner, W Klocker, H Horninger, W Conrads-Frank, A Sroczynski, G Siebert, U AF Muehlberger, Nikolai Kurzthaler, Christina Iskandar, Rowan Krahn, Murray D. Bremner, Karen E. Oberaigner, Willi Klocker, Helmut Horninger, Wolfgang Conrads-Frank, Annette Sroczynski, Gaby Siebert, Uwe TI The ONCOTYROL Prostate Cancer Outcome and Policy Model: Effect of Prevalence Assumptions on the Benefit-Harm Balance of Screening SO MEDICAL DECISION MAKING LA English DT Article DE decision analysis; Markov models; simulation methods; prostate cancer; cancer prevention ID SERVICES TASK-FORCE; COST-EFFECTIVENESS ANALYSIS; QUALITY-OF-LIFE; RECOMMENDATION STATEMENT; FOLLOW-UP; INTRAEPITHELIAL NEOPLASIA; POTENTIAL BENEFITS; DECISION-ANALYSIS; ANTIGEN; STRATEGIES AB Background. The ONCOTYROL Prostate Cancer Outcome and Policy (PCOP) model is a state-transition microsimulation model evaluating the benefits and harms of prostate cancer (PCa) screening. The natural history and detection component of the original model was based on the 2003 version of the Erasmus MIcrosimulation SCreening ANalysis (MISCAN) model, which was not calibrated to prevalence data. Compared with data from autopsy studies, prevalence of latent PCa assumed by the original model is low, which may bias the model toward screening. Our objective was to recalibrate the original model to match prevalence data from autopsy studies as well and compare benefit-harm predictions of the 2 model versions differing in prevalence. Methods. For recalibration, we reprogrammed the natural history and detection component of the PCOP model as a deterministic Markov state-transition cohort model in the statistical software package R. All parameters were implemented as variables or time-dependent functions and calibrated simultaneously in a single run. Observed data used as calibration targets included data from autopsy studies, cancer registries, and the European Randomized Study of Screening for Prostate Cancer. Compared models were identical except for calibrated parameters. Results. We calibrated 46 parameters. Prevalence from autopsy studies could not be fitted using the original parameter set. Additional parameters, allowing for interruption of disease progression and age-dependent screening sensitivities, were needed. Recalibration to higher prevalence demonstrated a considerable increase of overdiagnosis and decline of screening sensitivity, which significantly worsened the benefit-harm balance of screening. Conclusions. Our calibration suggests that not all cancers are at risk of progression, and screening sensitivity may be lower at older ages. PCa screening models that use calibration to simulate disease progression in the unobservable latent phase are highly sensitive to prevalence assumptions. C1 [Muehlberger, Nikolai; Kurzthaler, Christina; Iskandar, Rowan; Conrads-Frank, Annette; Sroczynski, Gaby; Siebert, Uwe] UMIT Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth & Hlth Technol Assessment, Tyrol, Austria. [Muehlberger, Nikolai; Kurzthaler, Christina; Iskandar, Rowan; Conrads-Frank, Annette; Sroczynski, Gaby; Siebert, Uwe] ONCOTYROL Ctr Personalized Canc Med, Div Hlth Technol Assessment & Bioinformat, Innsbruck, Austria. [Iskandar, Rowan] Univ Minnesota, Dept Hlth Policy & Management, Minneapolis, MN USA. [Krahn, Murray D.] Univ Toronto, THETA Collaborat, Toronto, ON, Canada. [Krahn, Murray D.; Bremner, Karen E.] Toronto Gen Hosp, Toronto Gen Res Inst, Toronto, ON, Canada. [Oberaigner, Willi] TILAK GmbH, Canc Registry Tyrol, Innsbruck, Austria. [Klocker, Helmut; Horninger, Wolfgang] Med Univ Innsbruck, Dept Urol, A-6020 Innsbruck, Austria. [Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Hlth Decis Sci, Boston, MA 02115 USA. [Siebert, Uwe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02115 USA. [Siebert, Uwe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. RP Siebert, U (reprint author), UMIT Univ Hlth Sci Med Informat & Tecnol, Eduard Wallnoefer Ctr 1, A-6060 Hall iT, A-6060 Tyrol, Austria. EM public-health@umit.at FU COMET Center ONCOTYROL; Austrian Federal Ministries BMVIT/BMWFJ (via FFG); Tiroler Zukunftsstiftung/Standortagentur Tirol (SAT) FX Financial support for this study was provided entirely by the COMET Center ONCOTYROL, which is funded by the Austrian Federal Ministries BMVIT/BMWFJ (via FFG) and the Tiroler Zukunftsstiftung/Standortagentur Tirol (SAT). The funding agreement ensured the authors' independence in designing the study, interpreting the data, writing, and publishing the report. Revision accepted for publication 6 April 2015. NR 71 TC 2 Z9 2 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X EI 1552-681X J9 MED DECIS MAKING JI Med. Decis. Mak. PD AUG PY 2015 VL 35 IS 6 BP 758 EP 772 DI 10.1177/0272989X15585114 PG 15 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA CO8NX UT WOS:000359427600009 PM 25977360 ER PT J AU Maharshak, N Ryu, HS Fan, TJ Onyiah, JC Schulz, S Otterbein, SL Wong, R Hansen, JJ Otterbein, LE Carroll, IM Plevy, SE AF Maharshak, Nitsan Ryu, Hyungjin Sally Fan, Ting-Jia Onyiah, Joseph C. Schulz, Stephanie Otterbein, Sherrie L. Wong, Ron Hansen, Jonathan J. Otterbein, Leo E. Carroll, Ian M. Plevy, Scott E. TI Escherichia coli heme oxygenase modulates host innate immune responses SO MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE carbon monoxide; chuS; enteric microbiota; heme oxygenase ID CARBON-MONOXIDE SUPPRESSES; DENDRITIC CELLS; INTESTINAL INFLAMMATION; PSEUDOMONAS-AERUGINOSA; MURINE COLITIS; T-CELLS; MICE; TRANSCRIPTION; EXPOSURE; EXPRESSION AB Induction of mammalian heme oxygenase (HO)-1 and exposure of animals to carbon monoxide (CO) ameliorates experimental colitis. When enteric bacteria, including Escherichia coli, are exposed to low iron conditions, they express an HO-like enzyme, chuS, and metabolize heme into iron, biliverdin and CO. Given the abundance of enteric bacteria residing in the intestinal lumen, our postulate was that commensal intestinal bacteria may be a significant source of CO and those that express chuS and other Ho-like molecules suppress inflammatory immune responses through release of CO. According to real-time PCR, exposure of mice to CO results in changes in enteric bacterial composition and increases E. coli 16S and chuS DNA. Moreover, the severity of experimental colitis correlates positively with E. coli chuS expression in IL-10 deficient mice. To explore functional roles, E. coli were genetically modified to overexpress chuS or the chuS gene was deleted. Co-culture of chuS-overexpressing E. coli with bone marrow-derived macrophages resulted in less IL-12p40 and greater IL-10 secretion than in wild-type or chuS-deficient E. coli. Mice infected with chuS-overexpressing E. coli have more hepatic CO and less serum IL-12 p40 than mice infected with chuS-deficient E. coli. Thus, CO alters the composition of the commensal intestinal microbiota and expands populations of E. coli that harbor the chuS gene. These bacteria are capable of attenuating innate immune responses through expression of chuS. Bacterial HO-like molecules and bacteria-derived CO may represent novel targets for therapeutic intervention in inflammatory conditions. C1 [Maharshak, Nitsan; Ryu, Hyungjin Sally; Fan, Ting-Jia; Onyiah, Joseph C.; Hansen, Jonathan J.; Carroll, Ian M.; Plevy, Scott E.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Maharshak, Nitsan; Ryu, Hyungjin Sally; Fan, Ting-Jia; Onyiah, Joseph C.; Hansen, Jonathan J.; Carroll, Ian M.; Plevy, Scott E.] Univ N Carolina, Ctr GI Biol & Dis, Chapel Hill, NC USA. [Maharshak, Nitsan; Hansen, Jonathan J.; Plevy, Scott E.] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA. [Maharshak, Nitsan] Tel Aviv Univ, Sackler Fac Med, Tel Aviv Med Ctr, Dept Gastroenterol & Liver Dis, IL-6997801 Tel Aviv, Israel. [Onyiah, Joseph C.] Univ Colorado, Dept Med, Div Gastroenterol & Hepatol, Aurora, CO USA. [Onyiah, Joseph C.] Denver VA Med Ctr, Denver, CO 80220 USA. [Schulz, Stephanie; Wong, Ron; Otterbein, Leo E.] Stanford Univ, Sch Med, Dept Pediat, Div Neonatal & Dev Med, Stanford, CA 94305 USA. [Otterbein, Sherrie L.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02115 USA. RP Maharshak, N (reprint author), Tel Aviv Med Ctr & Sch Med, Dept Gastroenterol & Liver Dis, 6 Weizman St, IL-64239 Tel Aviv, Israel. EM nitsanm@tlvmc.gov.il FU National Institutes of Health [R01 DK54452]; Crohn's and Colitis Foundation of America Research Fellowship Award; Gastroenterology Research Training Grant [T32 DK007737]; Center for Gastrointestinal Biology and Disease [P30 DK034987] FX This work was supported by National Institutes of Health Grants R01 DK54452 (S.E.P.); a Crohn's and Colitis Foundation of America Research Fellowship Award (N.M.); a Gastroenterology Research Training Grant T32 DK007737 (J.C.O.); and the Center for Gastrointestinal Biology and Disease P30 DK034987 (Immunotechnologies and Histology Core). NR 46 TC 2 Z9 2 U1 2 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0385-5600 EI 1348-0421 J9 MICROBIOL IMMUNOL JI Microbiol. Immunol. PD AUG PY 2015 VL 59 IS 8 BP 452 EP 465 DI 10.1111/1348-0421.12282 PG 14 WC Immunology; Microbiology SC Immunology; Microbiology GA CP3NP UT WOS:000359787000003 PM 26146866 ER PT J AU Dai, DF Sasaki, K Lin, MY Smith, KD Nicosia, RF Alpers, CE Najafian, B AF Dai, Dao-Fu Sasaki, Kotaro Lin, Mercury Y. Smith, Kelly D. Nicosia, Roberto F. Alpers, Charles E. Najafian, Behzad TI Interstitial eosinophilic aggregates in diabetic nephropathy: allergy or not? SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE allergy; chronic injury; diabetic nephropathy; eosinophil; interstitial nephritis ID NONDIABETIC RENAL-DISEASE; PROTEINURIA; PREVALENCE; BIOPSIES AB Background. Interstitial eosinophilic aggregates (IEA) in renal biopsies often suggest allergic tubulointerstitial nephritis, yet clear associations with drug reactions are often difficult to establish. IEA are also encountered in diabetic nephropathy (DN) and thought to be attributed to medication exposure. Methods. Native medical kidney biopsies performed at the University of Washington Medical Center were reviewed, including DN (n = 64), IgA nephropathy (IgAN, n = 28), membranous nephropathy (MN, n = 14), focal and segmental glomerulosclerosis (FSGS, n = 27) and membranoproliferative glomerulonephritis (MPGN, n = 28). IEA were defined as = 5 eosinophils per high power field. The severity of interstitial fibrosis and tubular atrophy (IFTA) was scored semi-quantitatively as minimal, mild, moderate or severe. Results. IEA were remarkably more prevalent in DN (41%), when compared with IgAN (7%, P = 0.001), MN (8%, P = 0.017) or MPGN (14%, P = 0.013), but not FSGS (26%, P = 0.18). In DN cases, univariate analysis revealed that IEA were associated with greater IFTA severity, but not with the percentage of glomerulosclerosis, mesangial expansion, history of drug allergy, number of prescribed medications or particular class of medications (antibiotics, NSAIDs, aspirin, thiazide, loop diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, beta blockers, insulin, sulfonylurea, metformin or allopurinol). Multivariate analysis showed that the severity of IFTA was the only significant predictor for IEA (P < 0.01) after stepwise adjustment for age, number of medications, drug allergy, diabetes type, % global glomerulosclerosis and mesangial expansion. Conclusions. Our study shows that IEA are more common in DN, when compared with other types of glomerulopathy. In DN, IEA are associated with the severity of IFTA but not with prescribedmedications or clinical history of allergy. This suggests that in DN IEA are often associated with chronic tubulointerstitial injury and are not diagnostic of an allergic interstitial nephritis. C1 [Dai, Dao-Fu; Sasaki, Kotaro; Lin, Mercury Y.; Smith, Kelly D.; Nicosia, Roberto F.; Alpers, Charles E.; Najafian, Behzad] Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA. [Nicosia, Roberto F.] VA Puget Sound Hlth Care Syst, Pathol & Lab Med Serv, Seattle, WA USA. RP Dai, DF (reprint author), Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA. EM ddaofu@yahoo.com; najafian@uw.edu NR 23 TC 1 Z9 1 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 EI 1460-2385 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD AUG PY 2015 VL 30 IS 8 BP 1370 EP 1376 DI 10.1093/ndt/gfv067 PG 7 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA CP3LP UT WOS:000359780800021 PM 25813275 ER PT J AU Machytka, E Thompson, CC Ryou, M Lautz, DB AF Machytka, Evzen Thompson, Christopher C. Ryou, Marvin Lautz, David B. TI CASE OF HYBRID LAPAROSCOPIC/ENDOSCOPIC DELIVERY OF A MAGNETIC COMPRESSION ANASTOMOSIS DEVICE FOR ENTERAL BYPASS SO OBESITY SURGERY LA English DT Meeting Abstract CT 20th World Congress of the International-Federation-for-the-Surgery-of-Obesity-and-Metabolic-Disord ers (IFSO) CY AUG 26-29, 2015 CL Vienna, AUSTRIA SP Int Federat Surg Obes & Metab Disorders C1 [Machytka, Evzen] Ostrava Univ Hosp, Ostrava, Czech Republic. [Thompson, Christopher C.; Ryou, Marvin] Brigham & Womens Hosp, Boston, MA 02115 USA. [Lautz, David B.] Emerson Hosp, Concord, MA USA. [Lautz, David B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0960-8923 EI 1708-0428 J9 OBES SURG JI Obes. Surg. PD AUG PY 2015 VL 25 SU 1 MA V.692 BP S144 EP S144 PG 1 WC Surgery SC Surgery GA CP0GF UT WOS:000359553100287 ER PT J AU Dove, ES Barlas, IO Birch, K Boehme, C Borda-Rodriguez, A Byne, WM Chaverneff, F Coskun, Y Dahl, ML Dereli, T Diwakar, S Elbeyli, L Endrenyi, L Eroglu-Kesim, B Ferguson, LR Gungor, K Gursoy, U Hekim, N Huzair, F Kaushik, K Kickbusch, I Kiroglu, O Kolker, E Kononen, E Lin, BY Llerena, A Malhan, F Nair, B Patrinos, GP Sardas, S Sert, O Srivastava, S Steuten, LMG Toraman, C Vayena, E Wang, W Warnich, L Ozdemir, V AF Dove, Edward S. Barlas, I. Omer Birch, Kean Boehme, Catharina Borda-Rodriguez, Alexander Byne, William M. Chaverneff, Florence Coskun, Yavuz Dahl, Marja-Liisa Dereli, Turkay Diwakar, Shyam Elbeyli, Levent Endrenyi, Laszlo Eroglu-Kesim, Belgin Ferguson, Lynnette R. Gungor, Kivanc Gursoy, Ulvi Hekim, Nezih Huzair, Farah Kaushik, Kabeer Kickbusch, Ilona Kiroglu, Olcay Kolker, Eugene Kononen, Eija Lin, Biaoyang Llerena, Adrian Malhan, Faruk Nair, Bipin Patrinos, George P. Sardas, Semra Sert, Ozlem Srivastava, Sanjeeva Steuten, Lotte M. G. Toraman, Cengiz Vayena, Effy Wang, Wei Warnich, Louise Ozdemir, Vural TI An Appeal to the Global Health Community for a Tripartite Innovation: An "Essential Diagnostics List," "Health in All Policies," and "See-Through 21(st) Century Science and Ethics" SO OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY LA English DT Review ID PERSONALIZED MEDICINE; RESPONSIBLE INNOVATION; NEXT-GENERATION; PHARMACOGENOMICS; GENOMICS; PROMISE; GOVERNANCE; ECOSYSTEM; CALL; AGE AB Diagnostics spanning a wide range of new biotechnologies, including proteomics, metabolomics, and nanotechnology, are emerging as companion tests to innovative medicines. In this Opinion, we present the rationale for promulgating an "Essential Diagnostics List." Additionally, we explain the ways in which adopting a vision for "Health in All Policies" could link essential diagnostics with robust and timely societal outcomes such as sustainable development, human rights, gender parity, and alleviation of poverty. We do so in three ways. First, we propose the need for a new, "see through" taxonomy for knowledge-based innovation as we transition from the material industries (e.g., textiles, plastic, cement, glass) dominant in the 20(th) century to the anticipated knowledge industry of the 21st century. If knowledge is the currency of the present century, then it is sensible to adopt an approach that thoroughly examines scientific knowledge, starting with the production aims, methods, quality, distribution, access, and the ends it purports to serve. Second, we explain that this knowledge trajectory focus on innovation is crucial and applicable across all sectors, including public, private, or public-private partnerships, as it underscores the fact that scientific knowledge is a co-product of technology, human values, and social systems. By making the value systems embedded in scientific design and knowledge co-production transparent, we all stand to benefit from sustainable and transparent science. Third, we appeal to the global health community to consider the necessary qualities of good governance for 21st century organizations that will embark on developing essential diagnostics. These have importance not only for science and knowledge-based innovation, but also for the ways in which we can build open, healthy, and peaceful civil societies today and for future generations. C1 [Dove, Edward S.] Univ Edinburgh, Sch Law, J Kenyon Mason Inst Med Life Sci & Law, Edinburgh, Midlothian, Scotland. [Barlas, I. Omer] Mersin Univ, Fac Med, Dept Med Biol & Genet, Mersin, Turkey. [Birch, Kean] York Univ, Fac Liberal Arts & Profess Studies, Dept Social Sci, Toronto, ON M3J 2R7, Canada. [Boehme, Catharina] Fdn Innovat New Diagnost, Geneva, Switzerland. [Borda-Rodriguez, Alexander] Secretaria Nacl Educ Super Ciencia Tecnol & Innov, Quito, Ecuador. [Borda-Rodriguez, Alexander] Open Univ, Dev Policy & Practice Grp, Milton Keynes MK7 6AA, Bucks, England. [Byne, William M.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Byne, William M.] James J Peters VA Med Ctr, Bronx, NY USA. [Chaverneff, Florence] NYU, Langone Med Ctr, Dept Neurosci & Physiol, New York, NY USA. [Coskun, Yavuz; Ozdemir, Vural] Gaziantep Univ, Off President, Gaziantep, Turkey. [Dahl, Marja-Liisa] Karolinska Inst, Div Clin Pharmacol, Stockholm, Sweden. [Dereli, Turkay; Ozdemir, Vural] Gaziantep Univ, Fac Engn, Dept Ind Engn, Gaziantep, Turkey. [Diwakar, Shyam; Nair, Bipin; Ozdemir, Vural] Amrita Univ, Amrita Vishwa Vidyapeetham, Amrita Sch Biotechnol, Kollam, Kerala, India. [Elbeyli, Levent] Gaziantep Univ, Fac Med, Gaziantep, Turkey. [Endrenyi, Laszlo] Univ Toronto, Fac Med, Dept Pharmacol, Toronto, ON M5S 1A1, Canada. [Eroglu-Kesim, Belgin] Sisli Etfal Res & Educ Hosp, Istanbul, Turkey. [Ferguson, Lynnette R.] Univ Auckland, Discipline Nutr, Auckland 1, New Zealand. [Gungor, Kivanc] Gaziantep Univ, Fac Hlth Sci, Gaziantep, Turkey. [Gursoy, Ulvi; Kononen, Eija] Univ Turku, Inst Dent, Dept Periodontol, Turku, Finland. [Hekim, Nezih] Beykent Univ, Sch Med, Istanbul, Turkey. [Huzair, Farah] Univ Edinburgh, Sch Social & Polit Sci, Sci Technol & Innovat Studies, Edinburgh, Midlothian, Scotland. [Kaushik, Kabeer] Vainteya Films Pvt Ltd, New Delhi, Delhi, India. [Kickbusch, Ilona] Grad Inst Int & Dev Studies, Global Hlth Program, Geneva, Switzerland. [Kiroglu, Olcay] Cukurova Univ, Fac Med, Dept Pharmacol, Adana, Turkey. [Kolker, Eugene] Seattle Childrens, Seattle Childrens Res Inst, Bioinformat & High Throughput Anal Lab, Seattle, WA USA. [Kolker, Eugene] Seattle Childrens, CDO Analyt, Seattle, WA USA. [Kolker, Eugene] Dept Biomed Informat & Med Educ, Seattle, WA USA. [Kolker, Eugene] Dept Pediat, Seattle, WA USA. [Kolker, Eugene] Univ Washington, Seattle, WA 98195 USA. [Kolker, Eugene; Ozdemir, Vural] Data Enabled Life Sci Alliance DELSA Global, Seattle, WA USA. [Kolker, Eugene] Northeastern Univ, Coll Sci, Dept Chem & Chem Biol, Boston, MA 02115 USA. [Lin, Biaoyang] Univ Washington, Dept Urol, Seattle, WA 98195 USA. [Lin, Biaoyang] Zhejiang Univ, Collaborat Innovat Ctr Diag & Treatment Infect Di, Hangzhou 310003, Zhejiang, Peoples R China. [Llerena, Adrian] Extremadura Univ Hosp & Med Sch, Badajoz, Extremadura, Spain. [Malhan, Faruk] Istanbul Design Fdn, Istanbul, Turkey. [Patrinos, George P.] Univ Patras, Sch Hlth Sci, Dept Pharm, Patras, Greece. [Sardas, Semra] Marmara Univ, Fac Pharm, Istanbul, Turkey. [Sert, Ozlem] Hacettepe Univ, Urban Studies Ctr, Ankara, Turkey. [Sert, Ozlem] Hacettepe Univ, Dept Hist, Ankara, Turkey. [Srivastava, Sanjeeva] Indian Inst Technol, Dept Biosci & Bioengn, Prote Lab, Bombay 400076, Maharashtra, India. [Steuten, Lotte M. G.] PANAXEA Bv, Enschede, Netherlands. [Steuten, Lotte M. G.] Univ Washington, Sch Pharm, Seattle, WA 98195 USA. [Toraman, Cengiz; Ozdemir, Vural] Gaziantep Univ, Fac Commun, Gaziantep, Turkey. [Toraman, Cengiz; Ozdemir, Vural] Gaziantep Univ, Dept Management Sci, Gaziantep, Turkey. [Vayena, Effy] Univ Zurich, Inst Biomed Eth, Zurich, Switzerland. [Wang, Wei] Edith Cowan Univ, Sch Med Sci, Perth, WA, Australia. [Wang, Wei] Capital Med Univ, Sch Publ Hlth, Beijing Municipal Key Lab Clin Epidemiol, Beijing, Peoples R China. [Warnich, Louise] Univ Stellenbosch, Fac Sci, ZA-7600 Stellenbosch, South Africa. RP Ozdemir, V (reprint author), Mary Ann Liebert Inc, 140 Huguenot St, New Rochelle, NY 10801 USA. EM OJIB@liebertpub.com RI Diwakar, Shyam/C-2455-2015 OI Diwakar, Shyam/0000-0003-1546-0184 FU TUBITAK (The Scientific and Technological Research Council of Turkey) 2232 Career Investigator Program FX No funding was received in support of this analysis. The views expressed are the personal opinions of the authors only and do not necessarily reflect the views of their affiliated institutions or funding agencies. VO is supported in part by TUBITAK (The Scientific and Technological Research Council of Turkey) 2232 Career Investigator Program. NR 37 TC 2 Z9 2 U1 4 U2 30 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1536-2310 EI 1557-8100 J9 OMICS JI OMICS PD AUG 1 PY 2015 VL 19 IS 8 BP 435 EP 442 DI 10.1089/omi.2015.0075 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA CO9ZH UT WOS:000359535100001 PM 26161545 ER PT J AU Wang, DC Deeney, V Roach, JW Shah, AJ AF Wang, David C. Deeney, Vincent Roach, James W. Shah, Amisha J. TI Imaging of physeal bars in children SO PEDIATRIC RADIOLOGY LA English DT Article DE Children; Computed tomography; Magnetic resonance imaging; Physeal bar; Physis; Radiography ID GROWTH-PLATE; BRIDGE FORMATION; EPIPHYSEAL; RABBITS; ABNORMALITIES; FRACTURE; INJURY AB The growth plate, also known as the physis or epiphyseal plate, is essential for longitudinal growth of bones in the immature skeleton. A variety of insults to the growth plate from trauma to infection to idiopathic causes can lead to physeal bar formation, an interruption in normal growth plate cartilage, where a bony or fibrous bridge develops between the metaphysis and epiphysis. This bridge restricts subsequent bone growth, leading to limb shortening and/or angular deformities. Early recognition of the presence of a physeal bar can help direct appropriate surgical management to restore linear growth of the bone. C1 [Wang, David C.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Deeney, Vincent; Roach, James W.] UPMC, Dept Orthoped, Childrens Hosp Pittsburgh, Pittsburgh, PA 15224 USA. [Shah, Amisha J.] UPMC, Dept Radiol, Childrens Hosp Pittsburgh, Pittsburgh, PA 15224 USA. RP Shah, AJ (reprint author), UPMC, Dept Radiol, Childrens Hosp Pittsburgh, 4401 Penn Ave, Pittsburgh, PA 15224 USA. EM shaha3@upmc.edu NR 25 TC 1 Z9 1 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 EI 1432-1998 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD AUG PY 2015 VL 45 IS 9 BP 1403 EP 1412 DI 10.1007/s00247-015-3280-5 PG 10 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA CO6UN UT WOS:000359292100015 PM 25786604 ER PT J AU Banks, CA Bhama, PK Park, J Hadlock, CR Hadlock, TA AF Banks, Caroline A. Bhama, Prabhat K. Park, Jong Hadlock, Charles R. Hadlock, Tessa A. TI Clinician-Graded Electronic Facial Paralysis Assessment: The eFACE SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID INTRACLASS CORRELATION-COEFFICIENTS; NERVE GRADING SYSTEM; BELLS-PALSY; REANIMATION; DIAGNOSIS; ATTRACTIVENESS; SUNNYBROOK; MANAGEMENT; OUTCOMES; SURGERY AB Background: The subjective nature of facial aesthetics and the difficulties associated with quantifying facial function have made outcomes analysis in facial paralysis challenging. Clinicians rely on photographs, subjective descriptions, and scales, limiting assessment, communication among providers, and communication between providers and patients. The authors describe the development and validation of a comprehensive, electronic, clinician-graded facial function scale (eFACE), which generates an overall disfigurement score and offers simple graphic output for clinician communication, assessment of various interventions, and patient understanding. The eFACE application may be used in a variety of electronic devices, including smartphones, tablets, and computers. Methods: An instrument consisting of 16 items in a visual analogue scale format was developed to assess facial function and symmetry (the eFACE). Video recordings of subjects performing facial expressions were viewed, and the eFACE instrument was applied, along with an overall facial disfigurement score. A multiple regression analysis was performed to determine the best linear relationship between overall expert-determined disfigurement and the eFACE items. The resulting equation was tested by three independent facial nerve clinicians, using an additional series of patients, to determine both interrater and intrarater reliability of the instrument. Results: Multiple regression analysis produced good fit of eFACE parameters to overall expert-rated global facial disfigurement when dynamic parameters were weighted twice as heavily as static and synkinesis parameters. eFACE scores demonstrated very high interrater and intrarater reliability. Conclusion: The eFACE is a reliable, reproducible, and straightforward digital clinical measure with which to assess facial function and disfigurement in patients with facial paralysis. C1 [Banks, Caroline A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol Head & Neck Surg,Div Facial Plas, Boston, MA 02114 USA. Harvard Univ, Boston Childrens Hosp, Sch Med, Boston, MA 02114 USA. Bentley Univ, Dept Math Sci, Waltham, MA USA. Alaska Native Tribal Hlth Consortium, Alaska Native Med Ctr, Dept Otolaryngol Head & Neck Surg, Anchorage, AK USA. RP Banks, CA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol Head & Neck Surg,Div Facial Plas, 243 Charles St, Boston, MA 02114 USA. EM caroline_banks@meei.harvard.edu NR 36 TC 6 Z9 6 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD AUG PY 2015 VL 136 IS 2 BP 223E EP 230E DI 10.1097/PRS.0000000000001447 PG 8 WC Surgery SC Surgery GA CP2NY UT WOS:000359715100001 PM 26218397 ER PT J AU Unizony, S Menendez, ME Rastalsky, N Stone, JH AF Unizony, Sebastian Menendez, Mariano E. Rastalsky, Naina Stone, John H. TI Inpatient complications in patients with giant cell arteritis: decreased mortality and increased risk of thromboembolism, delirium and adrenal insufficiency SO RHEUMATOLOGY LA English DT Article DE vasculitis; GCA; mortality; deep vein thrombosis; pulmonary embolism; venous thromboembolism; thrombophilia; adrenal insufficiency; delirium ID AMERICAN-COLLEGE; POLYMYALGIA-RHEUMATICA; CARDIOVASCULAR-DISEASE; ELDERLY-PEOPLE; UNITED-STATES; THROMBOSIS; THERAPY; EVENTS; HOSPITALIZATIONS; GRANULOMATOSIS AB Objective: The morbidity and mortality of hospitalized GCA patients have been unexplored. The aim of this study was to analyse inpatient complications experienced by patients with GCA. Methods: We used the Nationwide Inpatient Sample database to study a large group of patients admitted for pneumonia, myocardial infarction (MI), ischaemic stroke and femoral neck fracture. Patients were divided into two groups based on whether or not they had a diagnosis of GCA upon admission. Outcomes evaluated included inpatient mortality and the occurrence of adrenal insufficiency, deep vein thrombosis, pulmonary embolism and delirium. Results: From 2008 to 2011, 8 203 447 patients >= 50 years of age were discharged from US hospitals after admission with pneumonia, MI, stroke and femoral neck fracture. Among these patients, 9311 (0.11%) had GCA. Admissions for pneumonia, stroke and hip fracture were more frequent in GCA patients compared with those without GCA, accounting for 41.5% vs 39.4%, 24.9% vs 19.8% and 15.4% vs 14.2% of hospitalizations, respectively (P <= 0.001). Admissions for MI were more common in non-GCA patients (26.6% vs 18.2%, P< 0.001). During hospitalization, 4.1% of the GCA patients died, compared with 4.8% of those without GCA [odds ratio (OR) 0.73, P< 0.001). The GCA population suffered significantly more often from deep vein thrombosis (OR 2.08, P< 0.001), pulmonary embolism (OR 1.58, P< 0.001), delirium (OR 1.60, P< 0.001) and adrenal insufficiency (OR 4.95, P< 0.001). Conclusion: Hospitalized GCA patients have lower mortality compared with the general inpatient population but greater risk of venous thromboembolism, delirium and adrenal insufficiency. C1 [Unizony, Sebastian; Rastalsky, Naina; Stone, John H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol,Allergy & Immunol Div, Boston, MA USA. [Menendez, Mariano E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Boston, MA USA. RP Unizony, S (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, Yawkey 2C,55 Fruit St, Boston, MA 02114 USA. EM sunizony@mgh.harvard.org NR 47 TC 4 Z9 4 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 EI 1462-0332 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD AUG PY 2015 VL 54 IS 8 BP 1360 EP 1368 DI 10.1093/rheumatology/keu483 PG 9 WC Rheumatology SC Rheumatology GA CP1WG UT WOS:000359667100005 PM 25667435 ER PT J AU Bartels, CM Wong, JC Johnson, SL Thorpe, CT Barney, NP Sheibani, N Smith, MA AF Bartels, Christie M. Wong, Joanna C. Johnson, Sophia L. Thorpe, Carolyn T. Barney, Neal P. Sheibani, Nader Smith, Maureen A. TI Rheumatoid arthritis and the prevalence of diabetic retinopathy SO RHEUMATOLOGY LA English DT Article DE RA; diabetes; retinopathy; microvascular; epidemiology ID ANTIINFLAMMATORY DRUGS; ANGIOGENESIS; MEDICARE; RISK; CARE AB Objective. RA increases vascular disease and angiogenesis, yet a 1964 Lancet report paradoxically linked RA to lower diabetic retinopathy. Our objective was to examine RA as a risk factor for diabetic retinopathy compared with other vascular risk factors. Methods. This cohort study compared the prevalence of diabetic retinopathy in diabetes patients with and without RA in a 5% Medicare sample. We analysed the impact of RA on the prevalence of diabetic retinopathy using multivariate logistic regression calculating adjusted rate ratios (ARRs) controlling for sociodemographics, co-morbidity and health utilization. Sensitivity analysis examined eye exam rates. Results. Among 256 331 Medicare diabetes patients, 5572 (2%) had RA. Diabetic retinopathy was less prevalent in patients with RA compared with those without RA (13.7% vs 16.1%, P <= 0.01). Compared with patients without RA, the adjusted model demonstrated that patients with diabetes and RA were 28% less likely to have diabetic retinopathy and 4% more likely to receive an eye exam [ARR 0.72 (95% CI 0.67, 0.77), ARR 1.04 (95% CI 1.02, 1.06)]. Conclusion. Findings support the 1964 paradox observing decreased diabetic retinopathy in patients with RA. These findings pose new questions regarding whether RA physiology or treatments protect against diabetic retinopathy and how intraocular factors vary in contrast to adverse vascular changes elsewhere. C1 [Bartels, Christie M.; Wong, Joanna C.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Div Rheumatol, Madison, WI 53706 USA. [Johnson, Sophia L.; Smith, Maureen A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA. [Thorpe, Carolyn T.] Univ Pittsburgh, Ctr Hlth Equ Res & Promot, VA Pittsburgh Healthcare Syst, Dept Pharm & Therapeut, Pittsburgh, PA USA. [Thorpe, Carolyn T.] Univ Pittsburgh, Sch Pharm, Pittsburgh, PA USA. [Barney, Neal P.; Sheibani, Nader] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI USA. [Smith, Maureen A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Family Med, Madison, WI USA. [Smith, Maureen A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Madison, WI USA. RP Bartels, CM (reprint author), UWMF Centennial Bldg,Room 4132,1685 Highland Ave, Madison, WI 53705 USA. EM cb4@medicine.wisc.edu FU Health Innovation Program and the Community-Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research (UW-ICTR) [ULTR000427, KL2TR000428] FX Funding: This work was supported by the Health Innovation Program and the Community-Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research (UW-ICTR) (ULTR000427 and KL2TR000428 to C.M.B.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 19 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 EI 1462-0332 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD AUG PY 2015 VL 54 IS 8 BP 1415 EP 1419 DI 10.1093/rheumatology/kev012 PG 5 WC Rheumatology SC Rheumatology GA CP1WG UT WOS:000359667100014 PM 25731768 ER PT J AU Struck, AF Westover, MB AF Struck, Aaron F. Westover, Michael B. TI Variability in clinical assessment of neuroimaging in temporal lobe epilepsy SO SEIZURE-EUROPEAN JOURNAL OF EPILEPSY LA English DT Article DE FDG-PET; MRI; Temporal lobe epilepsy; Inter-rater reliability ID SURGERY; MR AB Purpose: Neuroimaging is critical in deciding candidacy for epilepsy surgery. Currently imaging is primarily assessed qualitatively, which may affect patient selection and outcomes. Method: The epilepsy surgery database at MGH was reviewed for temporal lobectomy patients from the last 10 years. Radiology reports for MRI and FDG-PET were compared to the epilepsy conference consensus. First, specific findings of ipsi/contra hippocampal atrophy and T2 signal changes were directly compared. Next the overall impression of presence of hippocampal sclerosis (HS) for MRI and temporal hypometabolism for PET was used for sensitivity/specificity analysis. To assess predictive power of imaging findings logistic regression was used. Results: 104 subjects were identified. 70% of subjects were ILAE class I at 1-year. Radiology reports and the conference consensus differed in 31% of FDG-PET studies and 41% of MRIs. For PET most disagreement (50%) stemmed for discrepancy regarding contralateral temporal hypometabolism. For MRI discrepancy in ipsilateral hippocampal atrophy/T2 signal accounted for 59% of disagreements. When overall impression of the image was used the overall reliability between groups was high with only MRI sensitivity to detect HS (0.75 radiology, 0.91 conference, p = 0.02) was significantly different between groups. On logistic regression MRI was a significant predictor of HS, but still 36% of patients with normal MRI as read by both groups had HS on pathology. Conclusion: Despite some difference in specific radiologic findings, overall accuracy for MRI and PET is similar in clinical practice between radiology and conference; nonetheless there are still cases of hippocampal pathology not detected by standard imaging methods. (C) 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. C1 [Struck, Aaron F.; Westover, Michael B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Epilepsy, Boston, MA 02114 USA. RP Struck, AF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Epilepsy, Wang 735,55 Fruit St, Boston, MA 02114 USA. EM astruck@mgh.harvard.edu FU NIH-NINDS [K23 NS090900]; Rappaport Foundation; Andrew David Heitman Neuroendovascular Research Fund FX Dr. Westover was supported by grants from NIH-NINDS (K23 NS090900), The Rappaport Foundation, and the Andrew David Heitman Neuroendovascular Research Fund. Dr. Struck reports no disclosures. NR 9 TC 0 Z9 0 U1 1 U2 3 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1059-1311 EI 1532-2688 J9 SEIZURE-EUR J EPILEP JI Seizure PD AUG PY 2015 VL 30 BP 132 EP 135 DI 10.1016/j.seizure.2015.06.011 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CO9MW UT WOS:000359500900022 PM 26216698 ER PT J AU David, WS Chad, DA AF David, William S. Chad, David A. TI Neuromuscular Disorders Preface SO SEMINARS IN NEUROLOGY LA English DT Editorial Material C1 [David, William S.; Chad, David A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Neuromuscular Diagnost Ctr, Boston, MA 02114 USA. [David, William S.; Chad, David A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, EMG Lab, Boston, MA 02114 USA. RP David, WS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Neuromuscular Diagnost Ctr, 165 Cambridge St,Suite 820, Boston, MA 02114 USA. EM wdavid@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 1 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 2015 VL 35 IS 4 BP 325 EP 325 DI 10.1055/s-0035-1558971 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA CP3BO UT WOS:000359752000002 PM 26502756 ER PT J AU Fridman, V Reilly, MM AF Fridman, Vera Reilly, M. M. TI Inherited Neuropathies SO SEMINARS IN NEUROLOGY LA English DT Article DE hereditary neuropathy; Charcot-Marie-Tooth disease; hereditary sensory and motor neuropathy; hereditary sensory and autonomic neuropathy ID MARIE-TOOTH-DISEASE; ASCORBIC-ACID TREATMENT; MYELIN PROTEIN ZERO; SENSORY NEUROPATHY; HEREDITARY NEUROPATHY; PERIPHERAL NEUROPATHIES; ENDOPLASMIC-RETICULUM; MOLECULAR-GENETICS; PRESSURE PALSIES; MFN2 MUTATIONS AB Hereditary neuropathies (HNs) are among the most common inherited neurologic disorders and are diverse both clinically and genetically. Recent genetic advances have contributed to a rapid expansion of identifiable causes of HN and have broadened the phenotypic spectrum associated with many of the causative mutations. The underlying molecular pathways of disease have also been better delineated, leading to the promise for potential treatments. This chapter reviews the clinical and biological aspects of the common causes of HN and addresses the challenges of approaching the diagnostic workup of these conditions in a rapidly evolving genetic landscape. C1 [Fridman, Vera] Massachusetts Gen Hosp, Neuromuscular Diagnost Ctr, Dept Neurol, Boston, MA 02114 USA. [Reilly, M. M.] UCL Inst Neurol, MRC Ctr Neuromuscular Dis, London, England. [Reilly, M. M.] Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England. RP Fridman, V (reprint author), Massachusetts Gen Hosp, Neuromuscular Diagnost Ctr, 165 Cambridge St, Boston, MA 02114 USA. EM vfridman@partners.org FU Medical Research Council [MR/K000608/1] NR 101 TC 1 Z9 1 U1 1 U2 9 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 2015 VL 35 IS 4 BP 407 EP 423 DI 10.1055/s-0035-1558981 PG 17 WC Clinical Neurology SC Neurosciences & Neurology GA CP3BO UT WOS:000359752000010 PM 26502764 ER PT J AU Bowley, MP Ropper, AH AF Bowley, Michael P. Ropper, Allan H. TI Neuropathies in Systemic Disease SO SEMINARS IN NEUROLOGY LA English DT Article DE peripheral neuropathy; mononeuritis multiplex; inflammatory bowel disease; connective tissue disease; critical illness polyneuropathy ID PERIPHERAL NERVOUS-SYSTEM; CHRONIC-RENAL-FAILURE; INFLAMMATORY-BOWEL-DISEASE; PRIMARY SJOGRENS-SYNDROME; CRITICAL ILLNESS POLYNEUROPATHY; ACRODERMATITIS CHRONICA ATROPHICANS; ANGIOTENSIN-CONVERTING ENZYME; UREMIC TUMORAL CALCINOSIS; MULTIPLE ORGAN FAILURE; SMALL FIBER NEUROPATHY AB Most peripheral neuropathies result from systemic disease. In this review, the authors highlight the main clinical features, electrographic abnormalities, histopathological aspects and treatment, as well as the current, but still incomplete understanding of the pathophysiological mechanisms involved. The peripheral neuropathic manifestations of renal failure, gastrointestinal illness, bariatric surgery, thyroid dysfunction, connective tissue disease, certain viral and bacterial infections, and critical illness are emphasized. C1 [Bowley, Michael P.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Ropper, Allan H.] Harvard Univ, Sch Med, Dept Neurol, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Bowley, MP (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,WACC 835, Boston, MA 02114 USA. EM mpbowley@partners.org NR 188 TC 0 Z9 0 U1 1 U2 3 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 2015 VL 35 IS 4 BP 431 EP 447 DI 10.1055/s-0035-1558978 PG 17 WC Clinical Neurology SC Neurosciences & Neurology GA CP3BO UT WOS:000359752000012 PM 26502766 ER PT J AU Salameh, JS Brown, RH Berry, JD AF Salameh, Johnny S. Brown, Robert H., Jr. Berry, James D. TI Amyotrophic Lateral Sclerosis: Review SO SEMINARS IN NEUROLOGY LA English DT Review DE amyotrophic lateral sclerosis; motor neuron disease; multidisciplinary care ID PERCUTANEOUS ENDOSCOPIC GASTROSTOMY; FRONTOTEMPORAL LOBAR DEGENERATION; QUALITY STANDARDS SUBCOMMITTEE; MOTOR-NEURON DISEASE; BODY-MASS INDEX; PROFESSIONAL FOOTBALL PLAYERS; PRACTICE PARAMETER UPDATE; SUPEROXIDE-DISMUTASE; AMERICAN ACADEMY; ALS PATIENTS AB Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease primarily affecting the upper and lower motor neurons. The lifetime risk of developing ALS is estimated at 1:350 for men and 1:500 for women, higher for those who have served in the military. The diagnosis remains clinical with electrodiagnostic support. Alternative diagnoses can usually be ruled out by the use of neuroimaging studies and laboratory evaluation. Perhaps because ALS is a diagnosis of exclusion, there is a substantial delay in diagnosis, upward of 12 months after the onset of symptoms, and most patients see three or more providers in the course of the diagnostic process. Once diagnosed, patients are best medically managed in a multidisciplinary care setting, an approach that has been shown to prolong survival and improve quality of life. Riluzole is the only disease-modifying therapy approved by the Food and Drug Administration, but numerous symptomatic therapies exist. In the past 20 years, ALS has become the focus of intense investigation by a worldwide community of basic scientists, and for clinical investigators the disease is an active area of research, with stem cell therapies, gene therapies, and a host of small molecule agents under investigation at various stages of clinical and preclinical development. C1 [Salameh, Johnny S.; Brown, Robert H., Jr.] Univ Massachusetts, Med Ctr, Dept Neurol, Mem Med Ctr, Worcester, MA 01655 USA. [Berry, James D.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Berry, JD (reprint author), Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM jdberry@partners.org NR 97 TC 5 Z9 5 U1 7 U2 40 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 2015 VL 35 IS 4 BP 469 EP 476 DI 10.1055/s-0035-1558984 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA CP3BO UT WOS:000359752000015 PM 26502769 ER PT J AU Wills, LP Beeson, GC Hoover, DB Schnellmann, RG Beeson, CC AF Wills, Lauren P. Beeson, Gyda C. Hoover, Douglas B. Schnellmann, Rick G. Beeson, Craig C. TI Assessment of ToxCast Phase II for Mitochondrial Liabilities Using a High-Throughput Respirometric Assay SO TOXICOLOGICAL SCIENCES LA English DT Article DE cell culture; in vitro and alternatives; kidney; systems toxicology; safety evaluation ID RAT-LIVER MITOCHONDRIA; OXIDATIVE-PHOSPHORYLATION; ENVIRONMENTAL CHEMICALS; PERMEABILITY TRANSITION; TOXICITY; CELLS; KIDNEY; BIOGENESIS; UNCOUPLERS; APOPTOSIS AB Previous high-throughput screens to identify mitochondrial toxicants used immortalized cell lines and focused on changes in mitochondrial membrane potential, which may not be sufficient and do not identify different types of mitochondrial dysfunction. Primary cultures of renal proximal tubule cells (RPTC) were examined with the Seahorse Extracellular Flux Analyzer to screen 676 compounds (5 mu M; 1 h) from the ToxCast Phase II library for mitochondrial toxicants. Of the 676 compounds, 19 were classified as cytotoxicants, 376 were electron transport chain (ETC) inhibitors, and 5 were uncouplers. The remaining 276 compounds were examined after a 5-h exposure to identify slower acting mitochondrial toxicants. This experiment identified 3 cytotoxicants, 110 ETC inhibitors, and 163 compounds with no effect. A subset of the ToxCast Phase II library was also examined in immortalized human renal cells (HK2) to determine differences in susceptibility to mitochondrial toxicity. Of the 131 RPTC ETC inhibitors tested, only 14 were ETC inhibitors in HK2 cells. Of the 5 RPTC uncouplers, 1 compound was an uncoupler in HK2 cells. These results demonstrate that 73% (491/676) of the compounds in the ToxCast Phase II library compounds exhibit RPTC mitochondrial toxicity, overwhelmingly ETC inhibition. In contrast, renal HK2 cells are markedly less sensitive and only identified 6% of the compounds as mitochondrial toxicants. We suggest caution is needed when studying mitochondrial toxicity in immortalized cell lines. This information will provide mechanisms and chemical-based criteria for assessing and predicting mitochondrial liabilities of new drugs, consumer products, and environmental agents. C1 [Wills, Lauren P.; Beeson, Gyda C.; Beeson, Craig C.] MitoHealth Inc, Charleston, SC USA. [Beeson, Gyda C.; Hoover, Douglas B.; Schnellmann, Rick G.; Beeson, Craig C.] Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA. [Schnellmann, Rick G.] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. RP Beeson, CC (reprint author), Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, 280 Calhoun St,QF309C, Charleston, SC 29403 USA. EM beesonc@musc.edu FU [2R44-ES019378-02] FX Funding for this project was provided through grant 2R44-ES019378-02. NR 37 TC 1 Z9 1 U1 2 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 EI 1096-0929 J9 TOXICOL SCI JI Toxicol. Sci. PD AUG PY 2015 VL 146 IS 2 BP 226 EP 234 DI 10.1093/toxsci/kfv085 PG 9 WC Toxicology SC Toxicology GA CP1IU UT WOS:000359630300003 PM 25926417 ER PT J AU Elnitsky, CA Powell-Cope, G Besterman-Dahan, KL Rugs, D Ullrich, PM AF Elnitsky, C. A. Powell-Cope, G. Besterman-Dahan, K. L. Rugs, D. Ullrich, P. M. TI Implementation of Safe Patient Handling in the US Veterans Health System: A Qualitative Study of Internal Facilitators' Perceptions SO WORLDVIEWS ON EVIDENCE-BASED NURSING LA English DT Article DE facilitation; facilitator; evidence-based practice; nursing practice; implementation; care delivery system; focus group; qualitative methodology ID INJURY PREVENTION PROGRAM; MUSCULOSKELETAL INJURY; ERGONOMICS PROGRAM; NURSING PERSONNEL; CARE AB BackgroundAlthough the literature has noted the positive effects of facilitation in implementation research, little is known about what facilitators do or how they increase adoption of a program. The purpose of this study was to understand internal facilitation activities in implementing a national safe patient handling program from the perspective of facility coordinators who implemented the program. MethodsUsing a qualitative descriptive design, data were collected in five focus groups at two international Safe Patient Handling and Mobility Conferences. Participants were 38 facility coordinators implementing a safe patient handling program in the Department of Veterans Affairs medical centers throughout the United States. Data were analyzed using direct content analysis to gather descriptions of internal facilitation. ResultsThe internal facilitation process involved engaging multiple disciplines and levels of leadership for implementation. Fifty-four facilitation activities were identified, including five activities not currently listed in an existing taxonomy. Key characteristics and skills of facilitators included persistence, credibility and clinical experience, and leadership and project management experience. Themes were mapped onto an existing framework and taxonomy of facilitation activities. Linking Evidence to ActionInternal facilitation is both an implementation intervention and a process involving a wide range of activities. The findings provide an understanding of what internal facilitators are doing to support practice changes and the characteristics and skills of internal facilitators that are likely to result in long-term organizational change. Five recommendations for action address organizations, senior leaders, and internal facilitators. C1 [Elnitsky, C. A.] Univ N Carolina, Charlotte, NC 28223 USA. [Elnitsky, C. A.; Powell-Cope, G.; Besterman-Dahan, K. L.; Rugs, D.] James A Haley Vet Hosp, Ctr Innovat Disabil & Rehabil Res CINDRR, Hlth Serv Res & Dev, Tampa, FL USA. [Ullrich, P. M.] VA Puget Sound Healthcare Syst, Dept Vet Affairs Spinal Cord Injury & Disorders S, Seattle, WA USA. [Ullrich, P. M.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP Elnitsky, CA (reprint author), Univ N Carolina, Coll Hlth & Human Serv 412A, 9201 Univ City Blvd, Charlotte, NC 28223 USA. EM celnitsky1@gmail.com FU Occupational Health Program, Veterans Health Administration Office of Public Health FX This study is the result of work funded through a research grant from the Director, Occupational Health Program, Veterans Health Administration Office of Public Health, and resources and use of facilities at the James A. Haley Veteran's Hospital, Tampa, FL. NR 23 TC 1 Z9 1 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-102X EI 1741-6787 J9 WORLDV EVID-BASED NU JI Worldviews Evid.-Based Nurs. PD AUG PY 2015 VL 12 IS 4 BP 208 EP 216 DI 10.1111/wvn.12098 PG 9 WC Nursing SC Nursing GA CO8MU UT WOS:000359424300004 PM 26220147 ER PT J AU Nucifora, PGP AF Nucifora, Paolo G. P. TI Overdiagnosis in the Era of Neuropsychiatric Imaging SO ACADEMIC RADIOLOGY LA English DT Article DE Neuroimaging; psychiatry; overdiagnosis ID POSTTRAUMATIC-STRESS-DISORDER; MAJOR DEPRESSIVE DISORDER; BORDERLINE PERSONALITY-DISORDER; OBSESSIVE-COMPULSIVE DISORDER; PREDICTS TREATMENT RESPONSE; VOXEL-BASED MORPHOMETRY; PATTERN-CLASSIFICATION; HIGH-RISK; 1ST-EPISODE SCHIZOPHRENIA; FUNCTIONAL CONNECTIVITY AB New guidelines proposed by the National Institute of Mental Health are intended to transform the management of patients with psychiatric disorders. It is anticipated that neuroimaging and other biomarkers will play a more prominent role in diagnosis and prognosis, especially in the prodromal phase of illness. Earlier treatment of psychiatric disorders has the potential to improve outcomes significantly. However, diagnosis in the absence of symptoms can lead to overdiagnosis. Overdiagnosis is a problem in many fields of medicine but could pose additional problems in psychiatry because of the stigmatization that often accompanies a diagnosis of mental illness. This review discusses the magnetic resonance imaging methods that hold the most promise for evaluating neuropsychiatric disorders, the likelihood that they could lead to overdiagnosis, and opportunities to minimize the impact of overdiagnosis in psychiatric disorders. C1 [Nucifora, Paolo G. P.] Philadelphia VA Med Ctr, Dept Radiol, Philadelphia, PA 19104 USA. [Nucifora, Paolo G. P.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. RP Nucifora, PGP (reprint author), Philadelphia VA Med Ctr, Dept Radiol, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM paolo.nucifora@va.gov NR 90 TC 1 Z9 1 U1 4 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 EI 1878-4046 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 2015 VL 22 IS 8 BP 995 EP 999 DI 10.1016/j.acra.2015.02.004 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CO6NO UT WOS:000359273600012 PM 25784322 ER PT J AU Ruutiainen, AT AF Ruutiainen, Alexander T. TI Utilization and Reporting of Bone Densitometry: What Can the Musculoskeletal Radiologist Do to Help, Rather Than to Hurt? SO ACADEMIC RADIOLOGY LA English DT Article DE DXA; densitometry; osteoporosis ID OSTEOPOROTIC FRACTURES; CLINICAL-USE; DENSITY; DISCORDANCE; OSTEOPENIA; OVERDIAGNOSIS; ALENDRONATE; SCORES; RISK AB Osteoporosis is a highly prevalent disease that predisposes patients to fragility fractures. These fractures carry serious risks, including increased mortality and the potential loss of functional independence. Effective treatments for osteoporosis are available, but these should be initiated before a fragility fracture actually occurs; to do so, osteoporosis must be diagnosed while it is still asymptomatic. The gold standard screening test used to detect low bone mass is dual-energy x-ray absorptiometry (DXA). Despite its clinical importance, the DXA report is sometimes neglected by radiologists-as though it were somehow less significant in diagnosis than our other modalities. If musculoskeletal radiologists are to-help, rather than to hurt, we must raise the profile of this critical test with evidence-based utilization and coherent reporting: detailed recommendations for doing so are available from professional organizations such as the International Society for Clinical Densitometry and the National Osteoporosis Foundation. This brief survey will seek to remind the radiologist that a good densitometry report requires more than just copying numbers from a scanner. C1 [Ruutiainen, Alexander T.] Philadelphia VA Med Ctr, Dept Radiol, Philadelphia, PA 19104 USA. [Ruutiainen, Alexander T.] Perelman Sch Med, Div Musculoskeletal Imaging, Dept Radiol, Philadelphia, PA USA. RP Ruutiainen, AT (reprint author), Philadelphia VA Med Ctr, Dept Radiol, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM Alexander.Ruutiainen@uphs.upenn.edu NR 29 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 1076-6332 EI 1878-4046 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 2015 VL 22 IS 8 BP 1030 EP 1033 DI 10.1016/j.acra.2015.02.008 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CO6NO UT WOS:000359273600019 PM 26100197 ER PT J AU Nemes, S Rolfson, O W-Dahl, A Garellick, G Sundberg, M Karrholm, J Robertsson, O AF Nemes, Szilard Rolfson, Ola W-Dahl, Annette Garellick, Goran Sundberg, Martin Karrholm, Johan Robertsson, Otto TI Historical view and future demand for knee arthroplasty in Sweden SO ACTA ORTHOPAEDICA LA English DT Article ID REVISION TOTAL HIP; UNITED-STATES; MODEL SELECTION; INFORMATION CRITERION; GLOBAL BURDEN; OSTEOARTHRITIS; REPLACEMENT; DISEASE; TRENDS; EPIDEMIOLOGY AB Background and purpose - The incidence of knee osteoarthritis will most likely increase. We analyzed historical trends in the incidence of knee arthroplasty in Sweden between 1975 and 2013, in order to be able to provide projections of future demand. Patients and methods - We obtained information on all knee arthroplasties in Sweden in the period 1975-2013 from the Swedish Knee Arthroplasty Register, and used public domain data from Statistics Sweden on the evolution of and forecasts for the Swedish population. We forecast the incidence, presuming the existence of a maximum incidence. Results - We found that the incidence of knee arthroplasty will continue to increase until a projected upper incidence level of about 469 total knee replacements per 10(5) Swedish residents aged 40 years and older is reached around the year 2130. In 2020, the estimated incidence of total knee arthroplasties per 10(5) Swedish residents aged 40 years and older will be 334 (95% prediction interval (PI): 281-374) and in 2030 it will be 382 (PI: 308-441). Using officially forecast population growth data, around 17,500 operations would be expected to be performed in 2020 and around 21,700 would be expected to be performed in 2030. Interpretation - Today's levels of knee arthroplasty are well below the expected maximum incidence, and we expect a continued annual increase in the total number of knee arthroplasties performed. C1 [Nemes, Szilard; Rolfson, Ola; Garellick, Goran; Karrholm, Johan] Swedish Hip Arthroplasty Register, Gothenburg, Sweden. [Rolfson, Ola; Garellick, Goran; Karrholm, Johan] Univ Gothenburg, Dept Orthoped, Inst Clin Sci, Sahlgrenska Acad, Gothenburg, Sweden. [Rolfson, Ola] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harris Orthopaed Lab, Boston, MA USA. [W-Dahl, Annette; Sundberg, Martin; Robertsson, Otto] Swedish Knee Arthroplasty Register, Lund, Sweden. [W-Dahl, Annette; Sundberg, Martin; Robertsson, Otto] Lund Univ, Dept Clin Sci, Orthoped, Lund, Sweden. RP Nemes, S (reprint author), Swedish Hip Arthroplasty Register, Gothenburg, Sweden. EM szilard.nemes@registercentrum.se OI Rolfson, Ola/0000-0001-6534-1242 NR 37 TC 3 Z9 3 U1 2 U2 7 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1745-3674 EI 1745-3682 J9 ACTA ORTHOP JI Acta Orthop. PD AUG PY 2015 VL 86 IS 4 BP 426 EP 431 DI 10.3109/17453674.2015.1034608 PG 6 WC Orthopedics SC Orthopedics GA CO4CC UT WOS:000359106700006 PM 25806653 ER PT J AU Dale, SK Weber, KM Cohen, MH Kelso, GA Cruise, RC Brody, LR AF Dale, Sannisha K. Weber, Kathleen M. Cohen, Mardge H. Kelso, Gwendolyn A. Cruise, Ruth C. Brody, Leslie R. TI Resilience Moderates the Association Between Childhood Sexual Abuse and Depressive Symptoms Among Women with and At-Risk for HIV SO AIDS AND BEHAVIOR LA English DT Article DE Resilience; Childhood sexual abuse; HIV; Depressive symptoms; Quality of life ID NATIONAL COMORBIDITY SURVEY; CONNOR-DAVIDSON RESILIENCE; QUALITY-OF-LIFE; SCALE CD-RISC; POSITIVE WOMEN; MULTISITE COHORT; INTERAGENCY HIV; PHYSICAL ABUSE; INFECTED WOMEN; MENTAL-HEALTH AB Childhood sexual abuse (CSA) places women at risk for HIV infection and once infected, for poor mental health outcomes, including lower quality of life and depressive symptoms. Among HIV-positive and demographically matched HIV-negative women, we investigated whether resilience and HIV status moderated the relationships between CSA and health indices as well as the relationships among CSA, depressive symptoms, and health-related quality of life (HRQOL). Participants included 202 women (138 HIV+, 64 HIV-, 87 % African American) from the Women's Interagency HIV Study Chicago CORE Center site. Results indicated that in both HIV-positive and HIV-negative women, higher resilience significantly related to lower depressive symptoms and higher HRQOL. CSA related to higher depressive symptoms only for women scoring low in resilience. Interventions to promote resilience, especially in women with a CSA history, might minimize depressive symptoms and poor HRQOL among HIV-positive and HIV-negative women. C1 [Dale, Sannisha K.; Kelso, Gwendolyn A.; Cruise, Ruth C.; Brody, Leslie R.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Dale, Sannisha K.] Massachusetts Gen Hosp, Behav Med Serv, Boston, MA 02114 USA. [Weber, Kathleen M.; Cohen, Mardge H.] Cook Cty Hlth & Hosp Syst, Dept Med, Chicago, IL USA. [Weber, Kathleen M.; Cohen, Mardge H.] John H Stroger Jr Hosp Cook Cty, CORE Ctr, Chicago, IL 60612 USA. [Cohen, Mardge H.] Rush Univ, Chicago, IL 60612 USA. RP Dale, SK (reprint author), Massachusetts Gen Hosp, Behav Med Serv, One Bowdoin Sq,Suite 701, Boston, MA 02114 USA. EM skdale@mgh.harvard.edu; lrbrody@gmail.com FU National Institute of Allergy and Infectious Diseases [U01-AI-34994]; National Cancer Institute; National Institute of Drug Abuse; National Research Service Award from National Institute of Mental Health [F31MH095510]; [P30-AI082151] FX Data in this manuscript were collected by the Chicago CORE Center site of the Women's Interagency HIV study (WIHS), which is funded by the National Institute of Allergy and Infectious Diseases Grant U01-AI-34994 (PI, Dr. Mardge Cohen) and co-funded by the National Cancer Institute and National Institute of Drug Abuse. Sannisha K. Dale was funded by a National Research Service Award (#F31MH095510) from the National Institute of Mental Health. Kathleen M. Weber was also funded in part by P30-AI082151. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the views of the National Institutes of Health. We are grateful to the WIHS participants in this study and to WIHS staff Cheryl Watson, Crystal Winston, Darlene Jointer, Sally Urwin, Maria Pyra, and Jane K. Burke-Miller who assisted with data collection and management. NR 58 TC 2 Z9 2 U1 2 U2 10 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD AUG PY 2015 VL 19 IS 8 BP 1379 EP 1387 DI 10.1007/s10461-014-0855-3 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA CO2VM UT WOS:000359014800001 PM 25085079 ER PT J AU Yehia, BR Stephens-Shield, AJ Momplaisir, F Taylor, L Gross, R Dube, B Glanz, K Brady, KA AF Yehia, Baligh R. Stephens-Shield, Alisa J. Momplaisir, Florence Taylor, Lynne Gross, Robert Dube, Benoit Glanz, Karen Brady, Kathleen A. TI Health Outcomes of HIV-Infected People with Mental Illness SO AIDS AND BEHAVIOR LA English DT Article DE Mental illness; HIV; Viral suppression; Retention; Antiretroviral therapy; Outcomes ID ACTIVE ANTIRETROVIRAL THERAPY; UNITED-STATES; BEHAVIORAL-CHARACTERISTICS; VIROLOGICAL RESPONSE; VIRAL SUPPRESSION; DRUG-USE; CARE; ADHERENCE; WOMEN; INTERVENTION AB Improving outcomes for people with HIV and mental illness will be critical to meeting the goals of the US National HIV/AIDS Strategy. In a retrospective analysis of the 2008-2010 cycles of the locally representative Philadelphia Medical Monitoring Project, we compared the proportions of HIV-infected adults with and without mental illness: (1) retained in care (a parts per thousand yen2 primary HIV visits separated by a parts per thousand yen90 days in a 12-month period); (2) prescribed antiretroviral therapy (ART) at any point in a 12-month period; and (3) virally suppressed (HIV-1 RNA a parts per thousand currency sign200 copies/mL at the last measure in the 12-month period). Multivariable regression assessed associations between mental illness and the outcomes, adjusting for age, gender, race/ethnicity, insurance, alcohol abuse, injection drug use, CD4 count, and calendar year. Of 730 HIV-infected persons, representative of 9409 persons in care for HIV in Philadelphia, 49.0 % had mental illness. In adjusted analyses, there were no significant differences in retention (91.3 vs. 90.3 %; AOR 1.30, 95 % CI 0.63-2.56) and prescription of ART (83.2 vs. 88.7 %; AOR 0.79, 95 % CI 0.49-1.25) between those with and without mental illness. However, mentally ill patients were less likely to achieve viral suppression than those without mental illness (65.9 vs. 74.4 %; AOR 0.64, 95 % CI 0.46-0.90). These findings argue for the need to optimize ART adherence in this population. C1 [Yehia, Baligh R.; Gross, Robert; Brady, Kathleen A.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Yehia, Baligh R.; Gross, Robert] Philadelphia Vet Affairs Ctr Hlth Equ Res & Promo, Philadelphia, PA USA. [Stephens-Shield, Alisa J.; Taylor, Lynne; Gross, Robert; Glanz, Karen] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Momplaisir, Florence] Drexel Univ, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Dube, Benoit] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Glanz, Karen] Univ Penn, Perelman Sch Med, Dept Biobehav Hlth Sci, Philadelphia, PA 19104 USA. [Brady, Kathleen A.] AIDS Act Coordinating Off, Dept Publ Hlth, Philadelphia, PA USA. RP Yehia, BR (reprint author), Univ Penn, Perelman Sch Med, Dept Med, 1021 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM byehia@upenn.edu FU National Institutes of Health [K23-MH097647]; Penn Mental Health AIDS Research Center [P30-MH097488]; Penn Center for AIDS Research [P30 AI 045008]; Centers for Disease Control and Prevention [PS13-130202 U62/003959] FX We would like to acknowledge the staff of the Philadelphia Department of Health AIDS Activities Coordinating Office including Jane Baker, Coleman Terrell and Mark Shpaner. This work was supported by the National Institutes of Health (K23-MH097647 to BRY), the Penn Mental Health AIDS Research Center (P30-MH097488), the Penn Center for AIDS Research (P30 AI 045008), and the Centers for Disease Control and Prevention (PS13-130202 #U62/003959 to KAB). NR 45 TC 0 Z9 0 U1 2 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD AUG PY 2015 VL 19 IS 8 BP 1491 EP 1500 DI 10.1007/s10461-015-1080-4 PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA CO2VM UT WOS:000359014800014 PM 25931243 ER PT J AU Palar, K Kushel, M Frongillo, EA Riley, ED Grede, N Bangsberg, D Weiser, SD AF Palar, Kartika Kushel, Margot Frongillo, Edward A. Riley, Elise D. Grede, Nils Bangsberg, David Weiser, Sheri D. TI Food Insecurity is Longitudinally Associated with Depressive Symptoms Among Homeless and Marginally-Housed Individuals Living with HIV SO AIDS AND BEHAVIOR LA English DT Article DE Food insecurity; Depression; HIV/AIDS; United States; Longitudinal ID INFECTED INDIVIDUALS; MENTAL-HEALTH; SAN-FRANCISCO; ANTIRETROVIRAL THERAPY; REPRESENTATIVE SAMPLE; PSYCHIATRIC-DISORDERS; WELFARE RECIPIENTS; CARE UTILIZATION; BURKINA-FASO; MEDICAL HOME AB Depression and food insecurity are prevalent among people with HIV (PLHIV) and contribute to poor HIV outcomes. Longitudinal data can help clarify the effect of food insecurity on depression among PLHIV in the United States. We assessed the longitudinal association of food insecurity with symptoms of depression using validated measures among participants living with HIV from the Research on Access to Care in the Homeless cohort in San Francisco. We followed 346 participants for a median of 28 months. Over half of participants (55.0 %) were food insecure and 35.8 % had symptoms of depression. In adjusted models, severe food insecurity in the previous period was associated with increased depressive symptom severity (b = 1.22; p < 0.001). The association remained statistically significant in models including participant fixed effects. Severe food insecurity was also longitudinally associated with a binary variable indicating probable depression. Efforts to increase access to and participation in food security safety net programs for PLHIV could improve depression. C1 [Palar, Kartika; Riley, Elise D.; Weiser, Sheri D.] UCSF, San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA 94110 USA. [Kushel, Margot] UCSF, San Francisco Gen Hosp, Div Gen Internal Med, San Francisco, CA 94110 USA. [Frongillo, Edward A.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Hlth Promot Educ & Behav, Columbia, SC 29208 USA. [Grede, Nils] United Nations World Food Programme, Rome, Italy. [Bangsberg, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Global Hlth,Ragon Inst MGH,MIT & Harvard, Boston, MA USA. [Bangsberg, David] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Weiser, Sheri D.] UCSF, Ctr AIDS Prevent Studies, San Francisco, CA 94110 USA. RP Palar, K (reprint author), UCSF, San Francisco Gen Hosp, Div HIV AIDS, 995 Potrero Ave,Bldg 80,Ward 84,Campus Box 0874, San Francisco, CA 94110 USA. EM kartika.palar@ucsf.edu FU NIMH [RO154907, K24 87227]; CHRP [ID08-SF-054]; UCSF Academic Senate; AIDS Research Institute award, UCSF [557858-8-148]; AHRQ [T32HS00046, R01 MH095683]; Burke Family Foundation FX This study was funded by NIMH RO154907 (PI: Dr Bangsberg) CHRP ID08-SF-054; UCSF Academic Senate; Hurlbut-Johnson funds from AIDS Research Institute award, UCSF, # 557858-8-148. The authors acknowledge the following additional sources of salary support: AHRQ T32HS00046 (Dr. Palar), R01 MH095683 and the Burke Family Foundation (Dr. Weiser), and NIMH K24 87227 (Dr. Bangsberg). NR 67 TC 12 Z9 12 U1 5 U2 11 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD AUG PY 2015 VL 19 IS 8 BP 1527 EP 1534 DI 10.1007/s10461-014-0922-9 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA CO2VM UT WOS:000359014800017 PM 25351185 ER PT J AU Wang, L Tan, TC Halpern, EF Neilan, TG Francis, SA Picard, MH Fei, HW Hochberg, EP Abramson, JS Weyman, AE Kuter, I Scherrer-Crosbie, M AF Wang, Lin Tan, Timothy C. Halpern, Elkan F. Neilan, Tomas G. Francis, Sanjeev A. Picard, Michael H. Fei, Hongwen Hochberg, Ephraim P. Abramson, Jeremy S. Weyman, Arthur E. Kuter, Irene Scherrer-Crosbie, Marielle TI Major Cardiac Events and the Value of Echocardiographic Evaluation in Patients Receiving Anthracycline-Based Chemotherapy SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CONGESTIVE-HEART-FAILURE; RADIONUCLIDE ANGIOCARDIOGRAPHY; DOXORUBICIN THERAPY; CARDIOTOXICITY; DYSFUNCTION; CARDIOMYOPATHY; TRASTUZUMAB; LYMPHOMA; TRIAL AB Anthracyclines are an important component of cancer treatments; however, their use is limited by the occurrence of cardiotoxicity. There are limited data on the occurrence of heart failure and the value of baseline and follow-up measurements of left ventricular (LV) ejection fraction (EF) in the current era. Therefore, the objectives of the present study were twofold: (1) to characterize the occurrence of and risk factors for major adverse cardiac events (MACEs: symptomatic heart failure and cardiac death) in a large contemporaneous population of adult patients treated with anthracyclines and (2) to test the value of LVEF and LV dimensions obtained using echocardiography in the prediction of MACE. Five thousand fifty-seven patients were studied, of whom 124 (2.4%) developed MACE. Of the total cohort, 2,285 patients had an available echocardiogram pre-chemotherapy. Patients with MACE were older (p <0.0001), predominantly men (p = 0.03), and with a higher incidence of cardiovascular risk factors and cardiac treatments. Patients with hematologic cancers had a higher incidence of cardiac events than patients with breast cancer (4.2% vs 0.7%, p <0.0001). Baseline LVEF, LVEF <= 5 points above the lower limits of normal, and LV internal diameter were predictive of the rate of occurrence of MACE. In conclusion, older patients with hematologic cancers and patients with a baseline LVEF <= 5 points above the lower limit of normal have higher incidence of MACE and should be closely monitored. (C) 2015 Elsevier Inc. All rights reserved. C1 [Wang, Lin; Tan, Timothy C.; Picard, Michael H.; Fei, Hongwen; Weyman, Arthur E.; Scherrer-Crosbie, Marielle] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab,Div Cardiol,Dept Med, Boston, MA 02138 USA. [Halpern, Elkan F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. [Neilan, Tomas G.; Francis, Sanjeev A.; Scherrer-Crosbie, Marielle] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiooncol Program,Div Cardiol,Dept Med, Boston, MA USA. [Hochberg, Ephraim P.; Abramson, Jeremy S.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Ctr Lymphoma,Med Sch, Boston, MA 02114 USA. [Kuter, Irene] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Ctr Breast Canc,Med Sch, Boston, MA 02114 USA. RP Scherrer-Crosbie, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab,Div Cardiol,Dept Med, Boston, MA 02138 USA. EM marielle@crosbie.com OI Picard, Michael/0000-0002-9264-3243 FU Susan G. Komen for the Cure Foundation [KG 080818] FX This work was supported by an investigator-initiated grant KG 080818 from the Susan G. Komen for the Cure Foundation to Dr., Scherrer-Crosbie. The authors have no conflict of interest to report. Drs Wang and Scherrer-Crosbie had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. NR 14 TC 7 Z9 7 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 1 PY 2015 VL 116 IS 3 BP 442 EP 446 DI 10.1016/j.amjcard.2015.04.064 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CO3CL UT WOS:000359034100017 PM 26071994 ER PT J AU Legget, KT Cornier, MA Rojas, DC Lawful, B Tregellas, JR AF Legget, Kristina T. Cornier, Marc-Andre Rojas, Donald C. Lawful, Benjamin Tregellas, Jason R. TI Harnessing the power of disgust: a randomized trial to reduce high-calorie food appeal through implicit priming SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE disgust; food preferences; implicit priming; nutrition; obesity ID EATING BEHAVIOR; LIKES; ASSOCIATIONS; PREFERENCES; ATTITUDES; DISLIKES; CHOICES AB Background: In our increasingly obesogenic environment, in which high-calorie convenience foods are readily available, food choices can drastically affect weight and overall health: Learned food preferences, which are developed through repeated pairings with positively and negatively valenced stimuli, can contribute to obesity susceptibility if positive attitudes toward high-calorie foods are developed. Thus, the modification of automatic associations with food may be a viable strategy to promote healthier eating behaviors. Objective: In this study, we investigated the ability of an implicit priming (IP) intervention to alter responses to visual food cues by using an evaluative conditioning approach. The main objective was to implicitly (i.e., below conscious perception) associate disgust with high-calorie foods with the aim of reducing liking of these foods. Design: Participants were randomly assigned to active or control IP. In active IP (n = 22), high-calorie food images were implicitly primed with negatively valenced images, and low-calorie food images were implicitly primed with positively valenced images. In control IP (n = 20), all food images were primed with neutral images of fixation crosses. Food images were rated on the desire to eat immediately before and after EP. Results: A significant main effect of calorie (high compared with low; P < 0.001) and a significant calorie-by-group (active compared with control) interaction (P = 0.025) were observed. Post hoc tests identified a significantly greater high-calorie rating decline after active IP than after control IP (P = 0.036). Furthermore, there was significantly greater change in high-calorie ratings than in low-calorie ratings in the active group (P = 0.001). Active IP effects extended to high-calorie foods not specifically included in the intervention, which suggested an effect generalization. Moreover, a greater change in high-calorie ratings than in low-calorie ratings persisted 3-5 d after active IP (P < 0.007), which suggested lasting effects. Conclusion: This study provides initial evidence that IP can be used to alter high-calorie food preferences, which could promote healthier eating habits. This trial was registered at clinicaltrials.gov as NCT02347527. C1 [Legget, Kristina T.; Lawful, Benjamin; Tregellas, Jason R.] Univ Colorado, Sch Med, Dept Med, Aurora, CO 80045 USA. [Cornier, Marc-Andre] Univ Colorado, Sch Med, Dept Med, Div Endocrinol Metab & Diabet, Aurora, CO USA. [Cornier, Marc-Andre] Univ Colorado, Anschutz Hlth & Wellness Ctr, Aurora, CO USA. [Rojas, Donald C.] Colorado State Univ, Dept Psychol, Ft Collins, CO 80523 USA. [Tregellas, Jason R.] Denver VA Med Ctr, Res Serv, Denver, CO USA. RP Legget, KT (reprint author), Univ Colorado, Sch Med, Dept Med, Anschutz Med Campus, Aurora, CO 80045 USA. EM kristina.legget@ucdenver.edu RI Tregellas, Jason/J-3637-2015; OI Rojas, Don/0000-0001-6560-9616; Legget, Kristina/0000-0002-2948-506X FU Colorado Nutrition Obesity Research Center [P30 DK048520]; National Institute of Mental Health [R01 MH102224]; National Institute of Diabetes and Digestive and Kidney Diseases [R21 DK102052, R01 DK089095, K01 DK100445] FX Supported by grants from the Colorado Nutrition Obesity Research Center (grant P30 DK048520; to KTL), the National Institute of Mental Health (grant R01 MH102224; to JRT), and the National Institute of Diabetes and Digestive and Kidney Diseases [grants R21 DK102052 (to JRT), R01 DK089095 (to M-AC and JRT), and K01 DK100445 (to KTL)]. NR 27 TC 1 Z9 1 U1 4 U2 19 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD AUG PY 2015 VL 102 IS 2 BP 249 EP 255 DI 10.3945/ajcn.115.106955 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CO3DW UT WOS:000359037800005 PM 26109580 ER PT J AU Mitchell, DM Leder, BZ Cagliero, E Mendoza, N Henao, MP Hayden, DL Finkelstein, JS Burnett-Bowie, SAM AF Mitchell, Deborah M. Leder, Benjamin Z. Cagliero, Enrico Mendoza, Natalia Henao, Maria P. Hayden, Douglas L. Finkelstein, Joel S. Burnett-Bowie, Sherri-Ann M. TI Insulin secretion and sensitivity in healthy adults with low vitamin D are not affected by high-dose ergocalciferol administration: a randomized controlled trial SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE vitamin D; ergocalciferol; insulin; diabetes; glucose; insulin resistance ID PLACEBO-CONTROLLED TRIAL; BETA-CELL FUNCTION; D-BINDING PROTEIN; SERUM 25-HYDROXYVITAMIN D; D SUPPLEMENTATION; METABOLIC SYNDROME; D DEFICIENCY; GLUCOSE-TOLERANCE; MODEL ASSESSMENT; D INSUFFICIENCY AB Background: Epidemiologic data suggest that low serum 25-hydroxyvitamin D [25(OH)D] increases insulin resistance and the risk of type 2 diabetes. Few interventional trials have assessed the effect of vitamin D on insulin metabolism, and published results are discordant. Objective: The goal of this study was to perform a detailed assessment of the effect of ergocalciferol administration on glucose and insulin metabolism in healthy people with low total 25(OH)D-total. Design: This was a 12-wk, double-blinded, randomized controlled trial. We enrolled 90 healthy volunteers aged 18-45 y with serum 25(OH)D <= 20 ng/mL (by immunoassay) and administered 50,000 IU ergocalciferol/wk or placebo for 12 wk. Primary endpoints were change in first-phase insulin response and insulin sensitivity as measured by intravenous glucose tolerance test. Secondary endpoints included change in homeostasis model assessment of insulin resistance; fasting glucose, insulin, and lipids; body mass index (BMI); and blood pressure. Results: On-study 25(OH)D-total was assessed by liquid chromatography-tandem mass spectrometry. In the treated group, 25(OH)D-total rose from 18 +/- 7 to 43 +/- 12 ng/mL (P < 0.001) with no change in the placebo group. Despite this increase, at 12 wk, there were no between-group differences in either insulin response or insulin sensitivity; nor were there differences in any measured secondary endpoints. There was no evidence of effect modification by sex, race, glucose tolerance status, baseline 25(OH)D-total, or BMI. Conclusion: In healthy persons with low 25(OH)D-total, ergocalciferol administration for 12 wk normalizes 25(OH)D-total but does not improve insulin secretion, insulin sensitivity, or other markers of metabolic health. This trial was registered at clinicaltrials.gov as NCT00491322. C1 [Mitchell, Deborah M.; Leder, Benjamin Z.; Mendoza, Natalia; Henao, Maria P.; Finkelstein, Joel S.; Burnett-Bowie, Sherri-Ann M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Mitchell, Deborah M.] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. [Cagliero, Enrico] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Hayden, Douglas L.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Mitchell, DM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM dmmitchell@mgh.harvard.edu OI Mitchell, Deborah/0000-0003-0364-9107 FU NIH [K23DK073356, 8UL1TR000170-05]; Fund for Medical Discovery Award; Massachusetts General Hospital Physician-Scientist Development Award; Boston Area Diabetes Endocrinology Research Center Award; Harvard Medical School Office for Diversity Inclusion and Community Partnership Award; Claflin Distinguished Scholar Award FX Supported by NIH grants K23DK073356 (S-AMB-B) and 8UL1TR000170-05 (Harvard Clinical and Translational Science Center), a Fund for Medical Discovery Award (DMM), a Massachusetts General Hospital Physician-Scientist Development Award (S-AMB-B), a Boston Area Diabetes Endocrinology Research Center Award (S-AMB-B), a Harvard Medical School Office for Diversity Inclusion and Community Partnership Award (S-AMB-B), and a Claflin Distinguished Scholar Award (S-AMB-B). NR 53 TC 3 Z9 3 U1 2 U2 8 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD AUG PY 2015 VL 102 IS 2 BP 385 EP 392 DI 10.3945/ajcn.115.111682 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CO3DW UT WOS:000359037800020 PM 26156733 ER PT J AU Weins, A Wong, JS Basgen, JM Gupta, R Daehn, I Casagrande, L Lessman, D Schwartzman, M Meliambro, K Patrakka, J Shaw, A Tryggvason, K He, JC Nicholas, SB Mundel, P Campbell, KN AF Weins, Astrid Wong, Jenny S. Basgen, John M. Gupta, Ritu Daehn, Ilse Casagrande, Lisette Lessman, David Schwartzman, Monica Meliambro, Kristin Patrakka, Jaakko Shaw, Andrey Tryggvason, Karl He, John Cijiang Nicholas, Susanne B. Mundel, Peter Campbell, Kirk N. TI Dendrin Ablation Prolongs Life Span by Delaying Kidney Failure SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; PARIETAL EPITHELIAL-CELLS; TYPE-1 DIABETIC-PATIENTS; PODOCYTE DEPLETION; NEPHROTIC SYNDROME; CD2-ASSOCIATED PROTEIN; GLOMERULAR HYPERTROPHY; IGA NEPHROPATHY; DISEASE; CD2AP AB Podocyte loss is central to the progression of proteinuric kidney diseases leading to end-stage kidney disease (ESKD), requiring renal replacement therapy, such as dialysis. Despite modern tools and techniques, the 5-year mortality of some patients requiring dialysis remains at about 70% to 80%. Thus, there is a great unmet need for podocyte-specific treatments aimed at preventing podocyte loss and the ensuing development of ESKD. Here, we show that ablation of the podocyte death-promoting protein dendrin delays the onset of ESKD, thereby expanding the life span of mice lacking the adapter protein CD2AP. Ablation of dendrin delays onset and severity of proteinuria and podocyte loss. In addition, dendrin ablation ameliorates mesangial volume expansion and up-regulation of mesangial fibronectin expression, which is mediated by a podocyte-secreted factor. In conclusion, onset of ESKD and death can be markedly delayed by blocking the function of dendrin. C1 [Weins, Astrid] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Weins, Astrid; Mundel, Peter] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. [Wong, Jenny S.; Daehn, Ilse; Casagrande, Lisette; Lessman, David; Schwartzman, Monica; Meliambro, Kristin; He, John Cijiang; Campbell, Kirk N.] Icahn Sch Med Mt Sinai, Div Nephrol, New York, NY 10029 USA. [Basgen, John M.] Charles R Drew Univ Med & Sci, Morphometry & Stereol Lab, Dept Res, Los Angeles, CA 90059 USA. [Patrakka, Jaakko] Karolinska Inst, Karolinska Univ Hosp Huddinge, Dept Med, KI AZ Integrated CardioMetabol Ctr ICMC, Stockholm, Sweden. [Gupta, Ritu] Albert Einstein Coll Med, Dept Pathol, Med, Bronx, NY 10467 USA. [Tryggvason, Karl] Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden. [Shaw, Andrey] Washington Univ, Sch Med, Div Immunobiol, St Louis, MO USA. [Nicholas, Susanne B.] Univ Calif Los Angeles, Div Nephrol, Los Angeles, CA USA. RP Campbell, KN (reprint author), Icahn Sch Med Mt Sinai, Div Nephrol, One Gustave L Levy Pl,Box 1243, New York, NY 10029 USA. EM kirk.campbell@mssm.edu OI daehn, ilse/0000-0001-9915-5376 FU NIH [DK081617, DK057683, DK062472, DK091218, DK093783]; NephCure Foundation; National Institute on Minority Health and Health Disparities [U54MD007598] FX Supported by NIH grant DK081617 and a NephCure Foundation Young Investigator grant (K.N.C.), NIH grants DK057683, DK062472, and DK091218 (P.M.), and NIH grant DK093783 (A.W.). Morphometric studies supported by the National Institute on Minority Health and Health Disparities (grant U54MD007598). JEM1200-EX electron microscope at the Electron Imaging Center for NanoMachines supported by NIH (1S10RR23057) and the California NanoSystems Institute at the University of California Los Angeles. NR 47 TC 5 Z9 5 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD AUG PY 2015 VL 185 IS 8 BP 2143 EP 2157 DI 10.1016/j.ajpath.2015.04.011 PG 15 WC Pathology SC Pathology GA CO3YD UT WOS:000359096300008 PM 26073036 ER PT J AU Mundinger, TO Cooper, E Coleman, MP Taborsky, GJ AF Mundinger, Thomas O. Cooper, Ellis Coleman, Michael P. Taborsky, Gerald J., Jr. TI Short-term diabetic hyperglycemia suppresses celiac ganglia neurotransmission, thereby impairing sympathetically mediated glucagon responses SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE nicotinic acetylcholine receptors; celiac ganglia; fos; sympathetic nervous system; norepinephrine; glucagon; WLDS ID WALLERIAN DEGENERATION; IN-VIVO; NERVE-STIMULATION; CELL-DEATH; HYPOGLYCEMIA; ACTIVATION; RAT; SECRETION; INSULIN; NEURONS AB Short-term hyperglycemia suppresses superior cervical ganglia neurotransmission. If this ganglionic dysfunction also occurs in the islet sympathetic pathway, sympathetically mediated glucagon responses could be impaired. Our objectives were 1) to test for a suppressive effect of 7 days of streptozotocin (STZ) diabetes on celiac ganglia (CG) activation and on neurotransmitter and glucagon responses to preganglionic nerve stimulation, 2) to isolate the defect in the islet sympathetic pathway to the CG itself, and 3) to test for a protective effect of the WLDS mutation. We injected saline or nicotine in nondiabetic and STZ-diabetic rats and measured fos mRNA levels in whole CG. We electrically stimulated the preganglionic or postganglionic nerve trunk of the CG in nondiabetic and STZ-diabetic rats and measured portal venous norepinephrine and glucagon responses. We repeated the nicotine and preganglionic nerve stimulation studies in nondiabetic and STZ-diabetic WLDS rats. In STZ-diabetic rats, the CG fos response to nicotine was suppressed, and the norepinephrine and glucagon responses to preganglionic nerve stimulation were impaired. In contrast, the norepinephrine and glucagon responses to postganglionic nerve stimulation were normal. The CG fos response to nicotine, and the norepinephrine and glucagon responses to preganglionic nerve stimulation, were normal in STZ-diabetic WLDS rats. In conclusion, short-term hyperglycemia's suppressive effect on nicotinic acetylcholine receptors of the CG impairs sympathetically mediated glucagon responses. WLDS rats are protected from this dysfunction. The implication is that this CG dysfunction may contribute to the impaired glucagon response to insulin-induced hypoglycemia seen early in type 1 diabetes. C1 [Mundinger, Thomas O.; Taborsky, Gerald J., Jr.] Univ Washington, Dept Med, Seattle, WA 98105 USA. [Cooper, Ellis] McGill Univ, Dept Physiol, Montreal, PQ, Canada. [Coleman, Michael P.] Babraham Inst, Cambridge, England. [Taborsky, Gerald J., Jr.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Mundinger, TO (reprint author), Univ Washington, Dept Med, Seattle, WA 98105 USA. EM mundin@u.washington.edu FU Biotechnology and Biological Sciences Research Council Institute Strategic Programme Grant; Canadian Institutes for Health Research; Medical Research Service of the Department of Veterans Affairs; National Institute of Health [R01 DK-50154] FX This work was supported by the Biotechnology and Biological Sciences Research Council Institute Strategic Programme Grant (M. P. Coleman), the Canadian Institutes for Health Research (E. Cooper), the Medical Research Service of the Department of Veterans Affairs (G. J. Taborsky, Jr.), and National Institute of Health Grant R01 DK-50154 (G. J. Taborsky, Jr.). NR 50 TC 1 Z9 1 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 EI 1522-1555 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD AUG 1 PY 2015 VL 309 IS 3 BP E246 EP E255 DI 10.1152/ajpendo.00140.2015 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA CO1VH UT WOS:000358943400005 PM 26037249 ER PT J AU Venkatesh, AK Curley, D Chang, YC Liu, SW AF Venkatesh, Arjun K. Curley, David Chang, Yuchiao Liu, Shan W. TI Communication of Vital Signs at Emergency Department Handoff: Opportunities for Improvement SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID ERRORS AB Study objective: We describe the prevalence of vital sign communication errors during emergency department (ED) handoffs. Our secondary objective is to evaluate the association between handoff behaviors and ED crowding on vital sign handoff errors. Methods: This was a prospective observational study of ED handoffs conducted at an urban academic hospital. We observed a prespecified convenience sample of ED shift rounds and included all patients whose care was subject to a handoff during ED shift change. The primary outcome was vital sign communication errors, defined as the failure to communicate an episode of medical-record-documented hypotension or hypoxia during ED shift rounds. Trained research assistants used a standardized data collection tool to collect data through direct observation and electronic health record abstraction. We report descriptive statistics and results of a logistic regression model constructed with generalized estimating equations to describe the association between handoff and rounds-level characteristics and handoff errors. Results: We observed 1,163 patient handoffs during 130 ED shift rounds. Of 117 patients with episodes of hypotension and 156 patients with hypoxia, 66 (42%) and 116 (74%) were not communicated at rounds, respectively. One hundred sixty-six handoffs (14%) included a vital sign communication error of omission. In multivariate analysis, no handoff or rounds characteristic, including the ED occupancy rate, was associated with omission errors of vital sign communication. Conclusion: Providers omitted communication of patient hypotension or hypoxia in nearly 1 in 7 ED handoffs. These communication errors do not appear to be related to ED crowding or care interruptions. C1 [Venkatesh, Arjun K.] Yale Univ, Sch Med, Dept Emergency Med, New Haven, CT 06510 USA. [Venkatesh, Arjun K.] Yale Univ, Sch Med, Robert Wood Johnson Fdn Clin Scholars Program, New Haven, CT USA. [Curley, David] Brown Univ, Dept Emergency Med, Warren Alpert Med Sch, Providence, RI 02912 USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02114 USA. [Liu, Shan W.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Venkatesh, AK (reprint author), Yale Univ, Sch Med, Dept Emergency Med, New Haven, CT 06510 USA. EM arjun.venkatesh@yale.edu FU Partners Healthcare Center of Expertise in Quality and Safety Resident Research Grant; Emergency Medicine Foundation Health Policy Scholar Award FX By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). The authors have stated that no such relationships exist and provided the following details: This work was supported by a Partners Healthcare Center of Expertise in Quality and Safety Resident Research Grant. Dr. Venkatesh received this grant as a resident in the Brigham and Women's Hospital-Massachusetts General Hospital-Harvard Affiliated Emergency Medicine Residency during the original conception and conduct of this work. Dr. Venkatesh is currently supported by the Emergency Medicine Foundation Health Policy Scholar Award. NR 14 TC 9 Z9 9 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD AUG PY 2015 VL 66 IS 2 BP 125 EP 130 DI 10.1016/j.annemergmed.2015.02.025 PG 6 WC Emergency Medicine SC Emergency Medicine GA CO0BP UT WOS:000358815400006 PM 25805116 ER PT J AU Warren, LEG Guo, H Regan, MM Nakhlis, F Yeh, ED Jacene, HA Hirshfield-Bartek, J Overmoyer, BA Bellon, JR AF Warren, Laura E. G. Guo, Hao Regan, Meredith M. Nakhlis, Faina Yeh, Eren D. Jacene, Heather A. Hirshfield-Bartek, Judi Overmoyer, Beth A. Bellon, Jennifer R. TI Inflammatory Breast Cancer: Patterns of Failure and the Case for Aggressive Locoregional Management SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID COMBINED-MODALITY THERAPY; PRIMARY TUMOR; NEOADJUVANT CHEMOTHERAPY; SURGICAL RESECTION; COMPETING RISK; SURVIVAL; CARCINOMA; OUTCOMES; RECURRENCE; DISEASE AB Inflammatory breast cancer (IBC) is a rare and aggressive subtype. This study analyzes the patterns of failure in patients with IBC treated at our institution. We retrospectively analyzed the records of 227 women with IBC presenting between 1997 and 2011. Survival analysis was used to calculate overall survival (OS) and disease-free survival. Competing risk analysis was used to calculate locoregional recurrence (LRR). A total of 173 patients had locoregional-only disease at presentation (non-MET). Median follow-up in the surviving patients was 3.3 years. Overall, 132 (76.3 %) patients received trimodality therapy with chemotherapy, surgery, and radiotherapy. Three-year OS was 73.1 % [95 % confidence interval (CI) 64.9-82.4]. Cumulative LRR was 10.1, 16.9, and 21.3 % at 1, 2, and 3 years, respectively. No variable was significantly associated with LRR. Fifty-four patients had metastatic disease at presentation (MET). Median follow-up in the surviving patients was 2.6 years. Three-year OS was 44.3 % (95 % CI 31.4-62.5). Twenty-four (44.4 %) patients received non-palliative local therapy (radiotherapy and/or surgery). For these patients, median OS after local therapy was 2 years. Excluding six patients who received local therapy for symptom palliation, the crude incidence of locoregional progression or recurrence (LRPR) was 17 % (4/24) for those who received local therapy compared with 57 % (13/23) for those who did not. For non-MET patients, LRR remains a problem despite trimodality therapy. More aggressive treatment is warranted. For MET patients, nearly 60 % have LRPR with systemic therapy alone. Local therapy should be considered in the setting of metastatic disease to prevent potential morbidity of progressive local disease. C1 [Warren, Laura E. G.] Harvard Radiat Oncol Program, Boston, MA 02139 USA. [Guo, Hao; Regan, Meredith M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Nakhlis, Faina] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Nakhlis, Faina; Yeh, Eren D.; Jacene, Heather A.; Hirshfield-Bartek, Judi; Overmoyer, Beth A.; Bellon, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Yeh, Eren D.] Brigham & Womens Hosp, Dept Radiol, Div Breast Imaging, Boston, MA 02115 USA. [Jacene, Heather A.] Brigham & Womens Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02115 USA. [Hirshfield-Bartek, Judi; Overmoyer, Beth A.] Brigham & Womens Hosp, Dept Med Oncol, Boston, MA 02115 USA. [Bellon, Jennifer R.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. RP Warren, LEG (reprint author), Harvard Radiat Oncol Program, Boston, MA 02139 USA. EM jbellon@lroc.harvard.edu RI Guo, Hao/E-8921-2015 OI Guo, Hao/0000-0003-1658-0989 NR 39 TC 3 Z9 3 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD AUG PY 2015 VL 22 IS 8 BP 2483 EP 2491 DI 10.1245/s10434-015-4469-4 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA CN8ZG UT WOS:000358734300007 PM 25791789 ER PT J AU Igarashi, H Kurihara, H Mitsuhashi, K Ito, M Okuda, H Kanno, S Naito, T Yoshii, S Takahashi, H Kusumi, T Hasegawa, T Sukawa, Y Adachi, Y Okita, K Hirata, K Imamura, Y Baba, Y Imai, K Suzuki, H Yamamoto, H Nosho, K Shinomura, Y AF Igarashi, Hisayoshi Kurihara, Hiroyoshi Mitsuhashi, Kei Ito, Miki Okuda, Hiroyuki Kanno, Shinichi Naito, Takafumi Yoshii, Shinji Takahashi, Hiroaki Kusumi, Takaya Hasegawa, Tadashi Sukawa, Yasutaka Adachi, Yasushi Okita, Kenji Hirata, Koichi Imamura, Yu Baba, Yoshifumi Imai, Kohzoh Suzuki, Hiromu Yamamoto, Hiroyuki Nosho, Katsuhiko Shinomura, Yasuhisa TI Association of MicroRNA-31-5p with Clinical Efficacy of Anti-EGFR Therapy in Patients with Metastatic Colorectal Cancer SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID CETUXIMAB PLUS IRINOTECAN; KRAS WILD-TYPE; BRAF MUTATION; COLON-CANCER; 1ST-LINE TREATMENT; RAS MUTATIONS; PHASE-III; EXPRESSION; PANITUMUMAB; SURVIVAL AB Gene mutations in the pathway downstream of epidermal growth factor receptor (EGFR) are considered to induce resistance to anti-EGFR therapy in colorectal cancer (CRC). We recently reported that microRNA-31 (miR-31)-5p may regulate BRAF activation and play a role in the signaling pathway downstream of EGFR in CRC. Therefore, we hypothesized that miR-31-5p can be a useful biomarker for anti-EGFR therapy in CRC. We evaluated miR-31-5p expression and gene mutations [KRAS (codon 61 or 146), NRAS (codon 12, 13, or 61), and BRAF (V600E)] in the EGFR downstream pathway in 102 CRC patients harboring KRAS (codon 12 or 13) wild-type who were treated with anti-EGFR therapeutics. Progression-free survival (PFS) and overall survival (OS) were evaluated. KRAS (codon 61 or 146), NRAS, and BRAF mutations were detected in 6.9, 6.9, and 5.9 % patients, respectively. Compared with CRCs with at least one mutation (n = 20), significantly better PFS (P = 0.0003) but insignificantly better OS were observed in CRCs harboring all wild-type genes (KRAS, NRAS, and BRAF). High miR-31-5p expression was identified in 11 % (n = 11) patients and was significantly associated with shorter PFS (P = 0.003). In CRCs carrying all wild-type genes, high miR-31-5p was associated with shorter PFS (P = 0.027). High miR-31-5p expression was associated with shorter PFS in patients with CRC treated with anti-EGFR therapeutics. Moreover, in CRCs carrying all wild-type genes, high miR-31-5p was associated with shorter PFS, suggesting that it may be a useful and additional prognostic biomarker for anti-EGFR therapy. C1 [Igarashi, Hisayoshi; Kurihara, Hiroyoshi; Mitsuhashi, Kei; Ito, Miki; Kanno, Shinichi; Naito, Takafumi; Sukawa, Yasutaka; Adachi, Yasushi; Nosho, Katsuhiko; Shinomura, Yasuhisa] Sapporo Med Univ, Sch Med, Dept Gastroenterol Rheumatol & Clin Immunol, Sapporo, Hokkaido, Japan. [Okuda, Hiroyuki] Keiyukai Sapporo Hosp, Dept Oncol, Sapporo, Hokkaido, Japan. [Yoshii, Shinji; Takahashi, Hiroaki] Keiyukai Sapporo Hosp, Dept Gastroenterol, Sapporo, Hokkaido, Japan. [Yoshii, Shinji] NTT East Sapporo Hosp, Dept Gastroenterol, Sapporo, Hokkaido, Japan. [Kusumi, Takaya] Keiyukai Sapporo Hosp, Dept Surg, Sapporo, Hokkaido, Japan. [Hasegawa, Tadashi] Sapporo Med Univ, Sch Med, Dept Pathol, Sapporo, Hokkaido, Japan. [Sukawa, Yasutaka] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Okita, Kenji; Hirata, Koichi] Sapporo Med Univ, Sch Med, Dept Surg Surg Oncol & Sci, Sapporo, Hokkaido, Japan. [Imamura, Yu; Baba, Yoshifumi] Kumamoto Univ, Grad Sch Med Sci, Dept Surg Gastroenterol, Kumamoto, Japan. [Imai, Kohzoh] Univ Tokyo, Inst Med Sci, Div Canc Res, Tokyo, Japan. [Suzuki, Hiromu] Sapporo Med Univ, Sch Med, Dept Mol Biol, Sapporo, Hokkaido, Japan. [Yamamoto, Hiroyuki] St Marianna Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, Kawasaki, Kanagawa, Japan. RP Igarashi, H (reprint author), Sapporo Med Univ, Sch Med, Dept Gastroenterol Rheumatol & Clin Immunol, Sapporo, Hokkaido, Japan. EM nosho@sapmed.ac.jp FU Japan Society for the Promotion of Science (JSPS) [23790800, 23390200]; A-STEP (Adaptable & Seamless, Technology Transfer Program through Target-driven RD); Sapporo Jikeikai Tomoiki Foundation; Takeda Science Foundation; Daiwa Securities Health Foundation FX The authors thank the pathology departments of Sapporo Medical University Hospital and Keiyukai Sapporo Hospital for providing the tissue specimens. The authors also thank Enago (www.enago.jp) for English language review. This work was supported by the Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research [Grant Numbers: 23790800 (to K.N.) and 23390200 (to Y.S.)], A-STEP (Adaptable & Seamless, Technology Transfer Program through Target-driven R&D) (to K.N.), Sapporo Jikeikai Tomoiki Foundation (to K.N.), Takeda Science Foundation (to K.N.), and Daiwa Securities Health Foundation (to H.I.). NR 51 TC 11 Z9 11 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD AUG PY 2015 VL 22 IS 8 BP 2640 EP 2648 DI 10.1245/s10434-014-4264-7 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA CN8ZG UT WOS:000358734300027 PM 25472647 ER PT J AU Tapias, LF Gilpin, SE Ren, X Wei, L Fuchs, BC Tanabe, KK Lanuti, M Ott, HC AF Tapias, Luis F. Gilpin, Sarah E. Ren, Xi Wei, Lan Fuchs, Bryan C. Tanabe, Kenneth K. Lanuti, Michael Ott, Harald C. TI Assessment of Proliferation and Cytotoxicity in a Biomimetic Three-Dimensional Model of Lung Cancer SO ANNALS OF THORACIC SURGERY LA English DT Article ID CIRCULATING TUMOR-CELLS; ORTHOTOPIC TRANSPLANTATION; 4D MODEL; TISSUE; MATRIX; DECELLULARIZATION; REGENERATION; TRANSITION; EXPRESSION; SCAFFOLDS AB Background. Decellularized whole-organ scaffolds show great potential in cancer research. They have been used in the biomimetic three-dimensional (3D) culture of non-small cell lung cancer cells, allowing the study of unique aspects of lung cancer biology. However, there are no reproducible assays capable of directly monitoring processes involved in cancer progression within such scaffolds. Methods. The human adenocarcinoma cell lines H358, PC9, and SW1573 were subjected to biomimetic 3D culture within decellularized lung scaffolds. A resazurin-based reagent was perfused through the scaffold to determine cell viability over the culture period and in response to treatment with cisplatin or erlotinib. Results. The resazurin reduction perfusion assay detected a progressive increase in the reduction of resazurin over time for all cell lines cultured within decellularized lung scaffolds, translating into incremental cell populations. Also, it detected a positive cytotoxic effect in H358- and PC9-seeded scaffolds after treatment with cisplatin, and in PC9-seeded scaffolds after treatment with erlotinib. Moreover, it identified relative resistance to erlotinib in H358-and SW1573-seeded scaffolds. Results from this assay correlated with histopathology, expression of caspase 3, and activity of epidermal growth factor receptor signaling. Conclusions. The methods described here for the monitoring of lung cancer cell viability under biomimetic 3D culture conditions within decellularized lung scaffolds permit the study of cancer cell proliferation, the evaluation of responses to therapeutic interventions, and the determination of relative chemo-sensitivities. (C) 2015 by The Society of Thoracic Surgeons C1 Massachusetts Gen Hosp, Ctr Regenerat Med, Div Thorac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Stem Cell Inst, Boston, MA USA. RP Ott, HC (reprint author), 185 Cambridge St,CPZN4800, Boston, MA 02114 USA. EM hott@mgh.harvard.edu FU US National Institutes of Health (NIH) Director's New Innovator Award [DP2 OD008749-01]; Department of Surgery at Massachusetts General Hospital FX This work was supported by the US National Institutes of Health (NIH) Director's New Innovator Award DP2 OD008749-01, and the Department of Surgery at Massachusetts General Hospital. NR 25 TC 3 Z9 3 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD AUG PY 2015 VL 100 IS 2 BP 414 EP 421 DI 10.1016/j.athoracsur.2015.04.035 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CN9VL UT WOS:000358798200017 PM 26141774 ER PT J AU Shih, T Paone, G Theurer, PF McDonald, D Shahian, DM Prager, RL AF Shih, Terry Paone, Gaetano Theurer, Patricia F. McDonald, Donna Shahian, David M. Prager, Richard L. TI The Society of Thoracic Surgeons Adult Cardiac Surgery Database Version 2.73: More Is Better SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 61st Annual Meeting of the Southern-Thoracic-Surgical-Association CY NOV 05-08, 2014 CL Tucson, AZ SP So Thorac Surg Assoc ID BYPASS-GRAFTING SURGERY; STAGE LIVER-DISEASE; QUALITY MEASUREMENT; VALVE SURGERY; CIRRHOSIS; RISK; MORTALITY; OPERATIONS; FRAILTY AB Background. With the introduction of version 2.73, several new patient risk factors are now captured in The Society of Thoracic Surgeons' (STS) Adult Cardiac Surgery Database. We sought to evaluate the potential association of these risk factors with mortality. Methods. We reviewed all patients with an STS predicted risk of mortality in our statewide quality collaborative database from July 2011 to September 2013 (N = 19,743). Univariate analyses were used to determine significant associations between mortality and the new risk factors in version 2.73. We then performed multivariable analysis, incorporating the STS predicted risk of mortality into our regression. Results. In the univariate model, patients with illicit drug use, syncope, unresponsive neurologic state, cancer within the last 5 years, current smoking history, other tobacco use, or sleep apnea had no significant difference in mortality (p > 0.05). Patients with liver disease, elevated Model for End-Stage Liver Disease score, mediastinal radiation, prolonged 5-meter walk test, home oxygen use, inhaled medications or bronchodilator therapy, decreased forced expiratory volume, and history of recent pneumonia had significant increases in operative mortality (p < 0.05). In multivariable analysis incorporating the STS predicted risk models, liver disease, elevated Model for End-Stage Liver Disease score, prolonged 5-meter walk test, home oxygen use, bronchodilator therapy, and abnormal pulmonary function tests were independently predictive of mortality. Conclusions. Several of the new STS data variables were significantly associated with operative mortality after cardiac surgery. The addition of these patient factors improves our understanding of evolving patient demographics and comorbid conditions and their impact on perioperative risk. This will improve both shared decision making and assessments of provider performance. (C) 2015 by The Society of Thoracic Surgeons C1 Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Cardiac Surg, Ann Arbor, MI 48109 USA. Henry Ford Hosp, Div Cardiac Surg, Detroit, MI 48202 USA. Michigan Soc Thorac & Cardiovasc Surg Qual Collab, Ann Arbor, MI USA. Soc Thorac Surg, Chicago, IL USA. Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Prager, RL (reprint author), Univ Michigan Hosp, Sect Adult Cardiac Surg, Ann Arbor, MI 48109 USA. EM rprager@umich.edu FU NHLBI NIH HHS [5T32HL07612309] NR 23 TC 4 Z9 5 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD AUG PY 2015 VL 100 IS 2 BP 516 EP 521 DI 10.1016/j.athoracsur.2015.02.085 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CN9VL UT WOS:000358798200031 PM 26052059 ER PT J AU Fitzsimons, MG Vlahakes, G Makar, R Dilley, J Wright, C Van Cott, EM Murali, M AF Fitzsimons, Michael G. Vlahakes, Gus Makar, Robert Dilley, Joshua Wright, Cameron Van Cott, Elizabeth M. Murali, Mandakolathur TI Deep Hypothermic Circulatory Arrest in a Patient With Cold-Induced Urticaria SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material ID BYPASS; MANAGEMENT AB Acquired cold urticaria is a condition characterized by the onset of pruritic hives, swelling, and occasional severe systemic reactions, during the rewarming phase, after cold exposure. Pulmonary thromboendarterectomy (PTE) is a cardiac surgical procedure where organized thrombus is excised from the pulmonary vasculature in order to improve pulmonary blood flow and relieve pressure on the right ventricle. A PTE requires institution of deep hypothermic circulatory arrest (DHCA) in order to reduce blood flow from collateral vessels during thrombus excision. We describe a case of PTE performed under DHCA in a patient with ACU. (C) 2015 by The Society of Thoracic Surgeons C1 Massachusetts Gen Hosp, Dept Anesthesia, Div Cardiac Anesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Crit Care, Div Cardiac Anesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pain Med, Div Cardiac Anesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiac Surg Div, Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Blood Transfus Serv, Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Thorac Surg Div, Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Coagulat Lab, Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Immunol Lab, Pathol, Boston, MA 02114 USA. RP Dilley, J (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM joshuaddilley@gmail.com NR 6 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 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD AUG PY 2015 VL 100 IS 2 BP 722 EP 723 DI 10.1016/j.athoracsur.2014.09.067 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CN9VL UT WOS:000358798200066 PM 26234851 ER PT J AU Heyanka, DJ Thaler, NS Linck, JF Pastorek, NJ Miller, B Romesser, J Sim, AH AF Heyanka, Daniel J. Thaler, Nicholas S. Linck, John F. Pastorek, Nicholas J. Miller, Brian Romesser, Jennifer Sim, Anita H. TI A Factor Analytic Approach to the Validation of the Word Memory Test and Test of Memory Malingering as Measures of Effort and Not Memory SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE Forensic neuropsychology; Head injury; traumatic brain injury; Malingering/symptom validity testing; Learning and Memory ID TRAUMATIC BRAIN-INJURY; PSYCHOGENIC NONEPILEPTIC SEIZURES; SYMPTOM VALIDITY TEST; DISABILITY INCENTIVES; COGNITIVE IMPAIRMENT; EXTERNAL INCENTIVES; HEAD-INJURY; TEST-SCORES; FAILURE; TOMM AB Research has demonstrated the utility of performance validity tests (PVTs) as a method of determining adequate effort during a neuropsychological evaluation. Although some studies affirm that forced-choice PVTs measure effort rather than memory, doubts remain in the literature. The purpose of the current study was to evaluate the relationship between effort and memory variables in a mild traumatic brain injury (TBI) sample (n = 160) by separating memory and effort as distinct factors while statistically controlling for the shared covariance between the variables. A two-factor solution was extracted such that the five PVT variables loaded on Factor 1 and the four memory variables loaded on Factor 2. The pattern matrix, which controls for the covariance between variables, provided clear support of two highly distinct factors with minimal cross-loadings. Our findings support assertions that PVTs measure effort independent of memory in veterans with mild TBI. C1 [Heyanka, Daniel J.] Bay Pines Dept Vet Affairs Med Ctr, Bay Pines, FL USA. [Thaler, Nicholas S.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Linck, John F.] Oklahoma City Dept Vet Affairs Med Ctr, Oklahoma City, OK USA. [Pastorek, Nicholas J.; Miller, Brian] Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX USA. [Romesser, Jennifer] George E Wahlen Dept Vet Affairs Med Ctr, Salt Lake City, UT USA. [Sim, Anita H.] Minneapolis VA Hlth Care Syst, Minneapolis, MN USA. RP Heyanka, DJ (reprint author), Bay Pines Dept Vet Affairs Med Ctr, Dept Mental Hlth & Behav Sci, Bay Pines, FL 33744 USA. EM dhneuropsych@gmail.com NR 32 TC 3 Z9 3 U1 4 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 EI 1873-5843 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD AUG PY 2015 VL 30 IS 5 BP 369 EP 376 DI 10.1093/arclin/acv025 PG 8 WC Psychology, Clinical; Psychology SC Psychology GA CO3PS UT WOS:000359071300002 PM 25964105 ER PT J AU Hilsabeck, RC Holdnack, JA Cullum, CM Drozdick, LW Edelstein, B Fiske, A Lacritz, L Mccoy, KJM Wahlstrom, D AF Hilsabeck, Robin C. Holdnack, James A. Cullum, C. Munro Drozdick, Lisa Whipple Edelstein, Barry Fiske, Amy Lacritz, Laura McCoy, Karin J. M. Wahlstrom, Dustin TI The Brief Cognitive Status Examination (BCSE): Comparing Diagnostic Utility and Equating Scores to the Mini-Mental State Examination (MMSE) SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE Cognitive screening; Dementia; Mild cognitive impairment ID SCREENING INSTRUMENTS; ASSESSMENT MOCA; PRIMARY-CARE; IMPAIRMENT; DEMENTIA; SCALE; PERFORMANCE; ACCURACY; STROKE; LEVEL AB The study purpose was to compare the diagnostic utility of the Brief Cognitive Status Exam (BCSE) to that of the Mini-Mental State Examination (MMSE) and to develop equated scores to facilitate comparisons. One hundred and eighty-two patients underwent cognitive evaluation and were placed into three groups: dementia (DEM), cognitive impairment, no dementia (CIND), and no cognitive impairment (NCI). One hundred and eighty-two healthy controls from the BCSE standardization sample served as a comparison group. On both measures, the DEM group obtained significantly lower scores than the other two groups, and the CIND group scored significantly lower than the NCI group. The BCSE was more sensitive in all clinical groups, although at extremely low scores, the two tests displayed similar sensitivity. Results indicate the BCSE has diagnostic utility as a cognitive screening measure in a mixed clinical sample and is more sensitive at detecting cognitive impairment, particularly milder levels, than the MMSE. C1 [Hilsabeck, Robin C.; McCoy, Karin J. M.] South Texas Vet Hlth Care Syst, Psychol Serv, San Antonio, TX 78229 USA. [Hilsabeck, Robin C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Holdnack, James A.; Drozdick, Lisa Whipple; Wahlstrom, Dustin] Pearson Inc, San Antonio, TX USA. [Cullum, C. Munro; Lacritz, Laura] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Cullum, C. Munro; Lacritz, Laura] Univ Texas SW Med Ctr Dallas, Dept Neurol, Dallas, TX 75390 USA. [Cullum, C. Munro; Lacritz, Laura] Univ Texas SW Med Ctr Dallas, Dept Neurotherapeut, Dallas, TX 75390 USA. [Edelstein, Barry; Fiske, Amy] W Virginia Univ, Dept Psychol, Morgantown, WV 26506 USA. RP Hilsabeck, RC (reprint author), South Texas Vet Hlth Care Syst, Psychol Serv, San Antonio, TX 78229 USA. EM hilsabeck@uthscsa.edu NR 43 TC 1 Z9 1 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 EI 1873-5843 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD AUG PY 2015 VL 30 IS 5 BP 458 EP 467 DI 10.1093/arclin/acv037 PG 10 WC Psychology, Clinical; Psychology SC Psychology GA CO3PS UT WOS:000359071300011 PM 26085478 ER PT J AU Yao, JX Tian, FH Rakvongthai, Y Oraintara, S Liu, HL AF Yao, Jixing Tian, Fenghua Rakvongthai, Yothin Oraintara, Soontorn Liu, Hanli TI Quantification and normalization of noise variance with sparsity regularization to enhance diffuse optical tomography SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID NEAR-INFRARED SPECTROSCOPY; SPATIAL-RESOLUTION; DEPTH LOCALIZATION; BRAIN ACTIVATION; LEAST-SQUARES; RECONSTRUCTION; OPTIMIZATION; ALGORITHM; DENSITY; MRI AB Conventional reconstruction of diffuse optical tomography (DOT) is based on the Tikhonov regularization and the white Gaussian noise assumption. Consequently, the reconstructed DOT images usually have a low spatial resolution. In this work, we have derived a novel quantification method for noise variance based on the linear Rytov approximation of the photon diffusion equation. Specifically, we have implemented this quantification of noise variance to normalize the measurement signals from all source-detector channels along with sparsity regularization to provide high-quality DOT images. Multiple experiments from computer simulations and laboratory phantoms were performed to validate and support the newly developed algorithm. The reconstructed images demonstrate that quantification and normalization of noise variance with sparsity regularization (QNNVSR) is an effective reconstruction approach to greatly enhance the spatial resolution and the shape fidelity for DOT images. Since noise variance can be estimated by our derived expression with relatively limited resources available, this approach is practically useful for many DOT applications. (C)2015 Optical Society of America C1 [Yao, Jixing; Oraintara, Soontorn] Univ Texas Arlington, Dept Elect Engn, Arlington, TX 76019 USA. [Tian, Fenghua; Liu, Hanli] Univ Texas Arlington, Dept Bioengn, Arlington, TX 76019 USA. [Rakvongthai, Yothin] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Rakvongthai, Yothin] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Yao, JX (reprint author), Univ Texas Arlington, Dept Elect Engn, Arlington, TX 76019 USA. EM oraintar@uta.edu; hanli@uta.edu NR 42 TC 0 Z9 0 U1 0 U2 5 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD AUG 1 PY 2015 VL 6 IS 8 BP 2961 EP 2979 DI 10.1364/BOE.6.002961 PG 19 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA CO2SD UT WOS:000359006000022 PM 26309760 ER PT J AU Clausen, DJ Smith, WB Haines, BE Wiest, O Bradner, JE Williams, RM AF Clausen, Dane J. Smith, William B. Haines, Brandon E. Wiest, Olaf Bradner, James E. Williams, Robert M. TI Modular synthesis and biological activity of pyridyl-based analogs of the potent Class I Histone Deacetylase Inhibitor Largazole SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE Largazole; Class I Histone Deacetylase Inhibitor; Pyridine analogs; Cytotoxic and biochemical assays ID MOLECULAR-DYNAMICS SIMULATIONS; AMBER FORCE-FIELD; BINDING; PROTEIN; DESIGN; MODEL; HDAC8 AB The formation of a series of analogs containing a pyridine moiety in place of the natural thiazole heterocycle, based on the potent, naturally occurring HDAC inhibitor Largazole has been accomplished. The synthetic strategy was designed modularly to access multiple inhibitors with different aryl functionalities containing both the natural depsipeptide and peptide isostere variant of the macrocycle. The cytotoxicity and biochemical activity of the library of HDAC inhibitors is described herein. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Clausen, Dane J.; Williams, Robert M.] Colorado State Univ, Dept Chem, Ft Collins, CO 80523 USA. [Smith, William B.; Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Haines, Brandon E.; Wiest, Olaf] Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA. [Bradner, James E.; Williams, Robert M.] Univ Colorado, Ctr Canc, Aurora, CO 80045 USA. RP Williams, RM (reprint author), Colorado State Univ, Dept Chem, Ft Collins, CO 80523 USA. EM robert.williams@colostate.edu OI Haines, Brandon/0000-0002-5013-8396 FU National Institutes of Health [1RO1 CA152314]; Colorado State University Cancer Supercluster; NIH Shared Instrument Grant [GM49631]; National Cancer Institute [1K08CA128972]; Burroughs-Wellcome Foundation (CAMS) FX This work was supported by the National Institutes of Health (Grant 1RO1 CA152314 to R.M.W., J.E.B. and O.W.). We also acknowledge financial support from the Colorado State University Cancer Supercluster.; Mass Spectra were obtained on instruments supported by the NIH Shared Instrument Grant GM49631. We thank Ralph Mazitschek for the provision of acetylated substrate. J.E.B. acknowledges support by grants from the National Cancer Institute (1K08CA128972) and the Burroughs-Wellcome Foundation (CAMS). We would also like to acknowledge Christine Dunne for her support with the manuscript. NR 30 TC 1 Z9 1 U1 3 U2 23 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 1 PY 2015 VL 23 IS 15 BP 5061 EP 5074 DI 10.1016/j.bmc.2015.03.063 PG 14 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA CN4ZV UT WOS:000358440000097 PM 26054247 ER PT J AU Zaborowski, MP Balaj, L Breakefield, XO Lai, CP AF Zaborowski, Mikolaj P. Balaj, Leonora Breakefield, Xandra O. Lai, Charles P. TI Extracellular Vesicles: Composition, Biological Relevance, and Methods of Study SO BIOSCIENCE LA English DT Article DE extracellular vesicles; exosomes; microvesicles; intercellular communication; methods ID CELL-DERIVED EXOSOMES; NANOPARTICLE TRACKING ANALYSIS; FLOW-CYTOMETRIC ANALYSIS; OVARIAN-CANCER; MEMBRANE-VESICLES; RECIPIENT CELLS; MESSENGER-RNA; INTERCELLULAR TRANSFER; DIAGNOSTIC BIOMARKERS; PROTEOMIC ANALYSIS AB The release of extracellular vesicles (EVs), including exosomes and microvesicles, is a phenomenon shared by many cell types as a means of communicating with other cells and also potentially removing cell contents. The cargo of EVs includes the proteins, lipids, nucleic acids, and membrane receptors of the cells from which they originate. EVs released into the extracellular space can enter body fluids and potentially reach distant tissues. Once taken up by neighboring and/or distal cells, EVs can transfer functional cargo that may alter the status of recipient cells, thereby contributing to both physiological and pathological processes. In this article, we will focus on BV composition, mechanisms of uptake, and their biological effects on recipient cells. We will also discuss established and recently developed methods used to study EVs, including isolation, quantification, labeling and imaging protocols, as well as RNA analysis. C1 [Zaborowski, Mikolaj P.; Balaj, Leonora; Breakefield, Xandra O.; Lai, Charles P.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Zaborowski, Mikolaj P.; Balaj, Leonora; Breakefield, Xandra O.; Lai, Charles P.] Harvard Univ, Sch Med, Harvard NeuroDiscovery Ctr, Boston, MA USA. [Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. [Zaborowski, Mikolaj P.] Poznan Univ Med Sci, Dept Gynecol Obstet & Gynecol Oncol, Poznan, Poland. RP Zaborowski, MP (reprint author), Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. EM mzaborowski@mgh.harvard.edu; balaj.leonora@magh.harvard.edu; breakefield@hms.harvard.edu; drcplai@gmail.com RI Lai, Charles/D-5442-2017 FU NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH [NIH NCI P01CA069246, NIH NCI U19 CA179563]; Richard Floor Biorepository Fund; FDM Fellowship (ECOR MGH); Kosciuszko Foundation; Poznan University of Medical Sciences FX We would like to thank Ms. Suzanne McDavitt for her supportive editorial assistance, Zofia Zaborowska for the graphical preparation of schematics, Sybren L.N. Maas for discussions on EV quantification methods, and Maria Ericsson for performing electron microscopy imaging. This work has been supported by NIH NCI P01CA069246 grant, NIH NCI U19 CA179563 supported by the NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH Director and the Richard Floor Biorepository Fund (MPZ, LB, XOB, CPL). LB is supported by the FDM Fellowship (ECOR MGH). Mikolaj Piotr Zaborowski is a recipient of a scholarship from the Kosciuszko Foundation and is thankful for support by the Poznan University of Medical Sciences. NR 96 TC 17 Z9 17 U1 5 U2 36 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-3568 EI 1525-3244 J9 BIOSCIENCE JI Bioscience PD AUG PY 2015 VL 65 IS 8 BP 783 EP 797 DI 10.1093/biosci/biv084 PG 15 WC Biology SC Life Sciences & Biomedicine - Other Topics GA CO5FA UT WOS:000359183800009 PM 26955082 ER PT J AU Kalebasi, N Kuelen, E Schnyder, U Schumacher, S Mueller-Pfeiffer, C Wilhelm, FH Athilingam, J Moergeli, H Martin-Soelch, C AF Kalebasi, Nilufer Kuelen, Eveline Schnyder, Ulrich Schumacher, Sonja Mueller-Pfeiffer, Christoph Wilhelm, Frank H. Athilingam, Jegath Moergeli, Hanspeter Martin-Soelch, Chantal TI Blunted responses to reward in remitted post-traumatic stress disorder SO BRAIN AND BEHAVIOR LA English DT Article DE Experimental; motivation; post-traumatic stress disorder; psychopathology; remitted; residual symptoms; reward ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; PREFRONTAL CORTEX; DSM-IV; PREDICTION; DECISION; SMOKERS; VERSION; MEMORY; MINI; FMRI AB BackgroundRecent evidence suggests blunted responses to rewarding stimuli in patients with post-traumatic stress disorder (PTSD). However, it is not clear whether these alterations in reward processing normalize in remitted PTSD patients. MethodsWe tested behavioral and physiological responses to monetary reward in a spatial memory task in 13 accident survivors with remitted PTSD, 14 accident survivors who never had PTSD, and 16 nontrauma-exposed subjects. All accident survivors were recruited from two samples of severely physically injured patients, who had participated in previous prospective studies on the incidence of PTSD after accidental injury approximately 10years ago. Reaction time, accuracy, skin conductance responses, and self-reported mood were assessed during the task. ResultsAccident survivors who never had PTSD and nontrauma exposed controls reported significantly higher positive mood in the reinforced versus nonreinforced condition (P<0.045 and P<0.001, respectively), while there was no effect of reinforcement in remitted PTSD subjects. ConclusionsOur findings suggest an alteration of the reward system in remitted PTSD. Further research is needed to investigate whether altered reward processing is a residual characteristic in PTSD after remission of symptoms or, alternatively, a preexisting risk factor for the development of PTSD after a traumatic event. C1 [Kalebasi, Nilufer; Schnyder, Ulrich; Schumacher, Sonja; Mueller-Pfeiffer, Christoph; Moergeli, Hanspeter] Univ Zurich, Univ Zurich Hosp, Dept Psychiat & Psychotherapy, Zurich, Switzerland. [Kuelen, Eveline] Cantonal Hosp Tessin, Bellinzona, Switzerland. [Mueller-Pfeiffer, Christoph] Ctr Educ & Res COEUR, Psychiat Serv Cty St Gallen North, Wil, Switzerland. [Mueller-Pfeiffer, Christoph] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Wilhelm, Frank H.] Salzburg Univ, Div Clin Psychol Psychotherapy & Hlth Psychol, A-5020 Salzburg, Austria. [Athilingam, Jegath] Univ Calif San Francisco, Ctr Integrat Neurosci, San Francisco, CA 94143 USA. [Martin-Soelch, Chantal] Univ Fribourg, Dept Psychol, Div Clin & Hlth Psychol, CH-1700 Fribourg, Switzerland. RP Martin-Soelch, C (reprint author), Univ Fribourg, Dept Psychol, Rue P-A Faucigny 6, CH-1700 Fribourg, Switzerland. EM chantal.martinsoelch@unifr.ch FU Department of Psychiatry and Psychotherapy at the University Hospital Zurich, Switzerland FX We thank the Department of Psychiatry and Psychotherapy at the University Hospital Zurich, Switzerland, for funding this research. NR 28 TC 0 Z9 0 U1 4 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 2162-3279 J9 BRAIN BEHAV JI Brain Behav. PD AUG PY 2015 VL 5 IS 8 AR e00357 DI 10.1002/brb3.357 PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA CO6YV UT WOS:000359305000009 PM 26357590 ER PT J AU Gay, ND Lee, SC Liel, MS Sochacki, P Recht, M Taylor, JA AF Gay, Nathan D. Lee, Sarah C. Liel, Meghan S. Sochacki, Paul Recht, Michael Taylor, Jason A. TI Increased fracture rates in people with haemophilia: a 10-year single institution retrospective analysis SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Letter DE haemophilia; fracture; bone disease; osteoporosis ID FACTOR-VIII DEFICIENCY; BONE-MINERAL DENSITY; OSTEOPOROSIS C1 [Gay, Nathan D.; Lee, Sarah C.; Taylor, Jason A.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Liel, Meghan S.; Recht, Michael; Taylor, Jason A.] Oregon Hlth & Sci Univ, Hemophilia Ctr, Portland, OR 97201 USA. [Sochacki, Paul] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA. [Taylor, Jason A.] Portland VA Med Ctr, Portland, OR USA. RP Gay, ND (reprint author), Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. EM taylojas@ohsu.edu NR 10 TC 7 Z9 7 U1 0 U2 1 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 2015 VL 170 IS 4 BP 584 EP 586 DI 10.1111/bjh.13312 PG 3 WC Hematology SC Hematology GA CO6IH UT WOS:000359259900018 PM 25659575 ER PT J AU Pectasides, E Bass, AJ AF Pectasides, Eirini Bass, Adam J. TI ERBB2 Emerges as a New Target for Colorectal Cancer SO CANCER DISCOVERY LA English DT Editorial Material ID MUTATIONS AB ERBB2 mutations and amplifications are present in 7% of colorectal cancers. The presence of these alterations may be a marker of resistance to anti-EGFR therapy and, more importantly, could help identify patients who would benefit from ERBB2-directed therapy. (C) 2015 AACR. C1 [Pectasides, Eirini] Beth Israel Deaconess Med Ctr, Div Hematol & Oncol, Boston, MA USA. [Pectasides, Eirini; Bass, Adam J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bass, Adam J.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Bass, Adam J.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Bass, Adam J.] Harvard Univ, Sch Med, Boston, MA USA. RP Bass, AJ (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM Adam_Bass@dfci.harvard.edu FU NCI NIH HHS [K08 CA134931, P01 CA098101, P01CA098101] NR 8 TC 2 Z9 2 U1 0 U2 1 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 2015 VL 5 IS 8 BP 799 EP 801 DI 10.1158/2159-8290.CD-15-0730 PG 3 WC Oncology SC Oncology GA CO7DF UT WOS:000359317700012 PM 26243861 ER PT J AU Skoulidis, F Byers, LA Diao, LX Papadimitrakopoulou, VA Tong, P Izzo, J Behrens, C Kadara, H Parra, ER Canales, JR Zhang, JJ Giri, U Gudikote, J Cortez, MA Yang, C Fan, YH Peyton, M Girard, L Coombes, KR Toniatti, C Heffernan, TP Choi, M Frampton, GM Miller, V Weinstein, JN Herbst, RS Wong, KK Zhang, JH Sharma, P Mills, GB Hong, WK Minna, JD Allison, JP Futreal, A Wang, J Wistuba, II Heymach, JV AF Skoulidis, Ferdinandos Byers, Lauren A. Diao, Lixia Papadimitrakopoulou, Vassiliki A. Tong, Pan Izzo, Julie Behrens, Carmen Kadara, Humam Parra, Edwin R. Canales, Jaime Rodriguez Zhang, Jianjun Giri, Uma Gudikote, Jayanthi Cortez, Maria A. Yang, Chao Fan, Youhong Peyton, Michael Girard, Luc Coombes, Kevin R. Toniatti, Carlo Heffernan, Timothy P. Choi, Murim Frampton, Garrett M. Miller, Vincent Weinstein, John N. Herbst, Roy S. Wong, Kwok-Kin Zhang, Jianhua Sharma, Padmanee Mills, Gordon B. Hong, Waun K. Minna, John D. Allison, James P. Futreal, Andrew Wang, Jing Wistuba, Ignacio I. Heymach, John V. TI Co-occurring Genomic Alterations Define Major Subsets of KRAS-Mutant Lung Adenocarcinoma with Distinct Biology, Immune Profiles, and Therapeutic Vulnerabilities SO CANCER DISCOVERY LA English DT Article ID TUMOR-CELL SURVIVAL; ADJUVANT CHEMOTHERAPY; CANCER-CELLS; SYSTEMATIC IDENTIFICATION; MATRIX FACTORIZATION; TARGETED THERAPIES; NRF2 ACTIVATION; GENE-EXPRESSION; LKB1 LOSS; MUTATIONS AB The molecular underpinnings that drive the heterogeneity of KRAS-mutant lung adenocarcinoma are poorly characterized. We performed an integrative analysis of genomic, transcriptomic, and proteomic data from early-stage and chemorefractory lung adenocarcinoma and identified three robust subsets of KRAS-mutant lung adenocarcinoma dominated, respectively, by co-occurring genetic events in STK11/LKB1 (the KL subgroup), TP53 (KP), and CDKN2A/B inactivation coupled with low expression of the NKX2-1 (TTF1) transcription factor (KC). We further revealed biologically and therapeutically relevant differences between the subgroups. KC tumors frequently exhibited mucinous histology and suppressed mTORC1 signaling. KL tumors had high rates of KEAP1 mutational inactivation and expressed lower levels of immune markers, including PD-L1. KP tumors demonstrated higher levels of somatic mutations, inflammatory markers, immune checkpoint effector molecules, and improved relapse-free survival. Differences in drug sensitivity patterns were also observed; notably, KL cells showed increased vulnerability to HSP90-inhibitor therapy. This work provides evidence that co-occurring genomic alterations identify subgroups of KRAS-mutant lung adenocarcinoma with distinct biology and therapeutic vulnerabilities. SIGNIFICANCE: Co-occurring genetic alterations in STK11/LKB1, TP53, and CDKN2A/B-the latter coupled with low TTF1 expression-define three major subgroups of KRAS-mutant lung adenocarcinoma with distinct biology, patterns of immune-system engagement, and therapeutic vulnerabilities. (C) 2015 AACR. C1 [Skoulidis, Ferdinandos; Byers, Lauren A.; Papadimitrakopoulou, Vassiliki A.; Behrens, Carmen; Gudikote, Jayanthi; Yang, Chao; Fan, Youhong; Heymach, John V.] Univ Texas MD Anderson Canc Ctr, Dept Thorac & Head & Neck Med Oncol, Houston, TX 77030 USA. [Diao, Lixia; Tong, Pan; Weinstein, John N.; Wang, Jing] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA. [Izzo, Julie; Kadara, Humam; Parra, Edwin R.; Canales, Jaime Rodriguez; Wistuba, Ignacio I.] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA. [Zhang, Jianjun; Futreal, Andrew] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA. [Cortez, Maria A.] Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA. [Peyton, Michael; Girard, Luc] Univ Texas SW Med Ctr Dallas, Hamon Ctr Therapeut Oncol, Dallas, TX 75390 USA. [Coombes, Kevin R.] Ohio State Univ, Dept Biomed Informat, Wexner Med Ctr, Columbus, OH 43210 USA. [Toniatti, Carlo; Heffernan, Timothy P.] Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Houston, TX 77030 USA. [Choi, Murim] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul, South Korea. [Frampton, Garrett M.; Miller, Vincent] Fdn Med, Cambridge, MA USA. [Herbst, Roy S.] Yale Canc Ctr, New Haven, CT USA. [Herbst, Roy S.] Smilow Canc Hosp Yale New Haven, New Haven, CT USA. [Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wong, Kwok-Kin] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA USA. [Sharma, Padmanee] Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA. [Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA. [Hong, Waun K.] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Houston, TX 77030 USA. [Allison, James P.] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA. RP Heymach, JV (reprint author), Univ Texas MD Anderson Canc Ctr, Unit 432,1515 Holcombe Blvd, Houston, TX 77030 USA. EM jheymach@mdanderson.org RI Tong, Pan/O-6097-2015 FU University of Texas Southwestern Medical Center; University of Texas MD Anderson Cancer Center Lung SPORE [5 P50 CA070907]; DoD PROSPECT grant [W81XWH-07-1-0306, 1 R01 CA155196-01]; Lung Cancer Moon Shot Program; M.D. Anderson Immunotherapy Platform; National Institute of Health Cancer Center Support Grant [CA016672, 1R01 CA168484-01]; V Foundation Grant; David Bruton, Jr. Endowed Chair; Ford Petrin donation; Jeanine T. Rainbolt Advanced Scholar Endowment; Eric and Pat Bodin Lung Cancer Research Fellowship; Uniting Against Lung Cancer Legacy Program for Advances in Lung Cancer Research grant FX This work was supported by The University of Texas Southwestern Medical Center and The University of Texas MD Anderson Cancer Center Lung SPORE grant 5 P50 CA070907; DoD PROSPECT grant W81XWH-07-1-0306; 1 R01 CA155196-01A1 (to V.A. Papadimitrakopoulou and R.S. Herbst); Lung Cancer Moon Shot Program; M.D. Anderson Immunotherapy Platform; National Institute of Health Cancer Center Support Grant (CA016672); 1R01 CA168484-01 (to J.V. Heymach); V Foundation Grant (to J.V. Heymach); the David Bruton, Jr. Endowed Chair (to J.V. Heymach); and a Ford Petrin donation. F. Skoulidis was supported by the Jeanine T. Rainbolt Advanced Scholar Endowment, the Eric and Pat Bodin Lung Cancer Research Fellowship, and a Uniting Against Lung Cancer Legacy Program for Advances in Lung Cancer Research grant. NR 58 TC 56 Z9 58 U1 10 U2 26 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 2015 VL 5 IS 8 BP 860 EP 877 DI 10.1158/2159-8290.CD-14-1236 PG 18 WC Oncology SC Oncology GA CO7DF UT WOS:000359317700019 PM 26069186 ER PT J AU Hoffmann, TJ Van den Eeden, SK Sakoda, LC Jorgenson, E Habel, LA Graff, RE Passarelli, MN Cario, CL Emami, NC Chao, CR Ghai, NR Shan, J Ranatunga, DK Quesenberry, CP Aaronson, D Presti, J Wang, ZM Berndt, SI Chanock, SJ McDonnell, SK French, AJ Schaid, DJ Thibodeau, SN Li, QY Freedman, ML Penney, KL Mucci, LA Haiman, CA Henderson, BE Seminara, D Kvale, MN Kwok, PY Schaefer, C Risch, N Witte, JS AF Hoffmann, Thomas J. Van den Eeden, Stephen K. Sakoda, Lori C. Jorgenson, Eric Habel, Laurel A. Graff, Rebecca E. Passarelli, Michael N. Cario, Clinton L. Emami, Nima C. Chao, Chun R. Ghai, Nirupa R. Shan, Jun Ranatunga, Dilrini K. Quesenberry, Charles P. Aaronson, David Presti, Joseph Wang, Zhaoming Berndt, Sonja I. Chanock, Stephen J. McDonnell, Shannon K. French, Amy J. Schaid, Daniel J. Thibodeau, Stephen N. Li, Qiyuan Freedman, Matthew L. Penney, Kathryn L. Mucci, Lorelei A. Haiman, Christopher A. Henderson, Brian E. Seminara, Daniela Kvale, Mark N. Kwok, Pui-Yan Schaefer, Catherine Risch, Neil Witte, John S. TI A Large Multiethnic Genome-Wide Association Study of Prostate Cancer Identifies Novel Risk Variants and Substantial Ethnic Differences SO CANCER DISCOVERY LA English DT Article ID SUSCEPTIBILITY LOCI; GENOTYPE IMPUTATION; GENETIC EPIDEMIOLOGY; SEQUENCE VARIANTS; AFRICAN ANCESTRY; FAMILY HISTORY; MULTIPLE LOCI; MEN; POPULATION; EXPRESSION AB A genome-wide association study (GWAS) of prostate cancer in Kaiser Permanente health plan members (7,783 cases, 38,595 controls; 80.3% non-Hispanic white, 4.9% African-American, 7.0% East Asian, and 7.8% Latino) revealed a new independent risk indel rs4646284 at the previously identified locus 6q25.3 that replicated in PEGASUS (N = 7,539) and the Multiethnic Cohort (N = 4,679) with an overall P = 1.0 x 10(-19) (OR, 1.18). Across the 6q25.3 locus, rs4646284 exhibited the strongest association with expression of SLC22A1 (P = 1.3 x 10(-23)) and SLC22A3 (P = 3.2 x 10(-52)). At the known 19q13.33 locus, rs2659124 (P = 1.3 x 10(-13); OR, 1.18) nominally replicated in PEGASUS. A risk score of 105 known risk SNPs was strongly associated with prostate cancer (P < 1.0 x 10(-8)). Comparing the highest to lowest risk score deciles, the OR was 6.22 for non-Hispanic whites, 5.82 for Latinos, 3.77 for African-Americans, and 3.38 for East Asians. In non-Hispanic whites, the 105 risk SNPs explained approximately 7.6% of disease heritability. The entire GWAS array explained approximately 33.4% of heritability, with a 4.3-fold enrichment within DNaseI hypersensitivity sites (P=0.004). SIGNIFICANCE: Taken together, our findings of independent risk variants, ethnic variation in existing SNP replication, and remaining unexplained heritability have important implications for further clarifying the genetic risk of prostate cancer. Our findings also suggest that there may be much promise in evaluating understudied variation, such as indels and ethnically diverse populations. (C) 2015 AACR. C1 [Hoffmann, Thomas J.; Graff, Rebecca E.; Passarelli, Michael N.; Cario, Clinton L.; Emami, Nima C.; Risch, Neil; Witte, John S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94158 USA. [Hoffmann, Thomas J.; Kvale, Mark N.; Kwok, Pui-Yan; Risch, Neil; Witte, John S.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94158 USA. [Van den Eeden, Stephen K.; Sakoda, Lori C.; Jorgenson, Eric; Habel, Laurel A.; Shan, Jun; Ranatunga, Dilrini K.; Quesenberry, Charles P.; Schaefer, Catherine; Risch, Neil] Kaiser Permanente, Div Res, Oakland, CA 94612 USA. [Van den Eeden, Stephen K.; Witte, John S.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94158 USA. [Chao, Chun R.; Ghai, Nirupa R.] Kaiser Permanente, Dept Res & Evaluat, Pasadena, CA 94612 USA. [Aaronson, David; Presti, Joseph] Kaiser Oakland Med Ctr, Dept Urol, Oakland, CA USA. [Wang, Zhaoming; Berndt, Sonja I.; Chanock, Stephen J.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. [McDonnell, Shannon K.; Schaid, Daniel J.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [French, Amy J.; Thibodeau, Stephen N.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Li, Qiyuan] Xiamen Univ, Coll Med, Xiamen, Peoples R China. [Freedman, Matthew L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Freedman, Matthew L.] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02115 USA. [Freedman, Matthew L.] Eli & Edythe L Broad Inst, Cambridge, MA USA. [Penney, Kathryn L.; Mucci, Lorelei A.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Penney, Kathryn L.; Mucci, Lorelei A.] Harvard Univ, Brigham & Womens Hosp, Channing Div Network Med, Dept Med,Med Sch, Boston, MA 02115 USA. [Haiman, Christopher A.; Henderson, Brian E.] Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. [Haiman, Christopher A.; Henderson, Brian E.] Univ So Calif, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90089 USA. [Seminara, Daniela] NCI, NIH, Bethesda, MD 20892 USA. [Witte, John S.] Univ Calif San Francisco, UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA. RP Witte, JS (reprint author), Univ Calif San Francisco, 1450 3rd St, San Francisco, CA 94158 USA. EM Stephen.Vandeneeden@kp.org; wittej@humgen.ucsf.edu FU NIH [CA127298, CA088164, CA112355, AG046616, DC013300, R01 GM107427, CA136578, CA141298, CA131945, CA151254, CA157881, CA63464, CA54281, CA1326792, CA148085, HG004726]; UCSF Goldberg-Benioff Program in Cancer Translational Biology; Prostate Cancer Foundation; Department of Defense [W81XWH-11-1-0261]; California Cancer Research Program [99-86883]; Community Benefit Program, Kaiser Permanente Northern California; National Institute on Aging; National Institute of Mental Health; NIH Common Fund [RC2 AG036607] FX This work was supported by NIH grants CA127298, CA088164, and CA112355 (to J.S. Witte); AG046616 and DC013300 (to T.J. Hoffmann); R01 GM107427 (to M.L. Freedman); CA136578, CA141298, and CA131945 (to K.L. Penney and L.A. Mucci); and CA151254 and CA157881 (to S.N. Thibodeau). This work was also supported by the UCSF Goldberg-Benioff Program in Cancer Translational Biology (to J.S. Witte), Prostate Cancer Foundation Young Investigator Awards (to K.L. Penney and L.A. Mucci), and Department of Defense grant W81XWH-11-1-0261 (to S.N. Thibodeau). The MEC and the genotyping in the African Ancestry Prostate Cancer GWAS Consortium (AAPC) were supported by NIH grants CA63464, CA54281, CA1326792, CA148085, and HG004726, funds from the California Cancer Research Program, grant number 99-86883, and from The Community Benefit Program, Kaiser Permanente Northern California. Support for participant enrollment, survey completion, and biospecimen collection for the RPGEH was provided by the Robert Wood Johnson Foundation, the Wayne and Gladys Valley Foundation, the Ellison Medical Foundation, and Kaiser Permanente national and regional community benefit programs. Genotyping of the GERA cohort was funded by a grant from the National Institute on Aging, the National Institute of Mental Health, and the NIH Common Fund (RC2 AG036607 to C. Schaefer and N. Risch). PEGASUS was supported by the Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH. NR 61 TC 13 Z9 13 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD AUG PY 2015 VL 5 IS 8 BP 878 EP 891 DI 10.1158/2159-8290.CD-15-0315 PG 14 WC Oncology SC Oncology GA CO7DF UT WOS:000359317700020 PM 26034056 ER PT J AU Tanizaki, J Ercan, D Capelletti, M Dodge, M Xu, CX Bahcall, M Tricker, EM Butaney, M Calles, A Sholl, LM Hammerman, PS Oxnard, GR Wong, KK Janne, PA AF Tanizaki, Junko Ercan, Dalia Capelletti, Marzia Dodge, Michael Xu, Chunxiao Bahcall, Magda Tricker, Erin M. Butaney, Mohit Calles, Antonio Sholl, Lynette M. Hammerman, Peter S. Oxnard, Geoffrey R. Wong, Kwok-Kin Jaenne, Pasi A. TI Identification of Oncogenic and Drug-Sensitizing Mutations in the Extracellular Domain of FGFR2 SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; ACTIVATING MUTATIONS; APERT-SYNDROME; GENE FUSIONS; LIGAND; ALK; CRANIOSYNOSTOSIS; GLYCOSYLATION; GLIOBLASTOMA AB The discovery of oncogenic driver mutations and the subsequent developments in targeted therapies have led to improved outcomes for subsets of lung cancer patients. The identification of additional oncogenic and drug-sensitive alterations may similarly lead to new therapeutic approaches for lung cancer. We identify and characterize novel FGFR2 extracellular domain insertion mutations and demonstrate that they are both oncogenic and sensitive to inhibition by FGFR kinase inhibitors. We demonstrate that the mechanism of FGFR2 activation and subsequent transformation is mediated by ligand-independent dimerization and activation of FGFR2 kinase activity. Both FGFR2-mutant forms are predominantly located in the endoplasmic reticulum and Golgi but nevertheless can activate downstream signaling pathways through their interactions with fibroblast growth factor receptor substrate 2 (FRS2). Our findings provide a rationale for therapeutically targeting this unique subset of FGFR2-mutant cancers as well as insight into their oncogenic mechanisms. (C)2015 AACR. C1 [Tanizaki, Junko; Ercan, Dalia; Capelletti, Marzia; Dodge, Michael; Xu, Chunxiao; Bahcall, Magda; Tricker, Erin M.; Butaney, Mohit; Calles, Antonio; Oxnard, Geoffrey R.; Wong, Kwok-Kin; Jaenne, Pasi A.] Lowe Ctr Thorac Oncol, Boston, MA USA. [Tanizaki, Junko; Ercan, Dalia; Capelletti, Marzia; Dodge, Michael; Xu, Chunxiao; Bahcall, Magda; Tricker, Erin M.; Butaney, Mohit; Calles, Antonio; Hammerman, Peter S.; Oxnard, Geoffrey R.; Wong, Kwok-Kin; Jaenne, Pasi A.] Dept Med Oncol, Boston, MA USA. [Sholl, Lynette M.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Hammerman, Peter S.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Oxnard, Geoffrey R.; Wong, Kwok-Kin; Jaenne, Pasi A.] Dept Med, Boston, MA USA. [Wong, Kwok-Kin; Jaenne, Pasi A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02215 USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,HIM223, Boston, MA 02215 USA. EM pasi_janne@dfci.harvard.edu OI Calles, Antonio/0000-0002-2547-1947 FU Uehara Memorial Foundation; Cammarata Family Foundation Research Fund; Nirenberg Fellowship at the Dana-Farber Cancer Institute; National Cancer Institute [K08 CA163677]; V Foundation Scholar Award FX This work is supported by The Uehara Memorial Foundation (J. Tanizaki), the Cammarata Family Foundation Research Fund (M. Capelletti and P.A. Janne), the Nirenberg Fellowship at the Dana-Farber Cancer Institute (M. Capelletti and P.A. Janne), and by the National Cancer Institute (K08 CA163677; P.S. Hammerman). P.S. Hammerman is supported by a V Foundation Scholar Award. NR 35 TC 7 Z9 7 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2015 VL 75 IS 15 BP 3139 EP 3146 DI 10.1158/0008-5472.CAN-14-3771 PG 8 WC Oncology SC Oncology GA CO7EU UT WOS:000359323200018 PM 26048680 ER PT J AU Moroco, JA Baumgartner, MP Rust, HL Choi, HG Hur, W Gray, NS Camacho, CJ Smithgall, TE AF Moroco, Jamie A. Baumgartner, Matthew P. Rust, Heather L. Choi, Hwan Geun Hur, Wooyoung Gray, Nathanael S. Camacho, Carlos J. Smithgall, Thomas E. TI A Discovery Strategy for Selective Inhibitors of c-Src in Complex with the Focal Adhesion Kinase SH3/SH2-binding Region SO CHEMICAL BIOLOGY & DRUG DESIGN LA English DT Article DE Src kinase; focal adhesion kinase; SH3 domain; SH2 domain; kinase inhibitors; cancer drug discovery ID PROTEIN-TYROSINE KINASES; SMALL-MOLECULE INHIBITORS; FAMILY KINASES; STRUCTURAL BASIS; SIGNAL-TRANSDUCTION; CRYSTAL-STRUCTURES; ABL KINASE; IN-VIVO; DOMAIN; CANCER AB The c-Src tyrosine kinase co-operates with the focal adhesion kinase to regulate cell adhesion and motility. Focal adhesion kinase engages the regulatory SH3 and SH2 domains of c-Src, resulting in localized kinase activation that contributes to tumor cell metastasis. Using assay conditions where c-Src kinase activity required binding to a tyrosine phosphopeptide based on the focal adhesion kinase SH3-SH2 docking sequence, we screened a kinase-biased library for selective inhibitors of the Src/focal adhesion kinase peptide complex versus c-Src alone. This approach identified an aminopyrimidinyl carbamate compound, WH-4-124-2, with nanomolar inhibitory potency and fivefold selectivity for c-Src when bound to the phospho-focal adhesion kinase peptide. Molecular docking studies indicate that WH-4-124-2 may preferentially inhibit the 'DFG-out' conformation of the kinase active site. These findings suggest that interaction of c-Src with focal adhesion kinase induces a unique kinase domain conformation amenable to selective inhibition. C1 [Moroco, Jamie A.; Rust, Heather L.; Smithgall, Thomas E.] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA 15219 USA. [Baumgartner, Matthew P.; Camacho, Carlos J.] Univ Pittsburgh, Sch Med, Dept Computat & Syst Biol, Pittsburgh, PA 15260 USA. [Choi, Hwan Geun; Hur, Wooyoung; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Choi, Hwan Geun; Hur, Wooyoung; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Smithgall, TE (reprint author), Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, 450 Technol Dr, Pittsburgh, PA 15219 USA. EM tsmithga@pitt.edu OI Baumgartner, Matthew/0000-0002-1279-9038 FU National Institutes of Health [CA169962, GM097082]; Pittsburgh AIDS Research Training Program [NIH T32 AI065380] FX This work was supported by National Institutes of Health grants CA169962 to T. E. S. and GM097082 to C. J. C. J. A. M. was supported by the Pittsburgh AIDS Research Training Program (NIH T32 AI065380). NR 55 TC 1 Z9 1 U1 2 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-0277 EI 1747-0285 J9 CHEM BIOL DRUG DES JI Chem. Biol. Drug Des. PD AUG PY 2015 VL 86 IS 2 BP 144 EP 155 DI 10.1111/cbdd.12473 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA CO5RJ UT WOS:000359215900002 PM 25376742 ER PT J AU Palacio, F Reyes, LF Levine, DJ Sanchez, JF Angel, LF Fernandez, JF Levine, SM Rello, J Abedi, A Restrepo, MI AF Palacio, Federico Reyes, Luis F. Levine, Deborah J. Sanchez, Juan F. Angel, Luis F. Fernandez, Juan F. Levine, Stephanie M. Rello, Jordi Abedi, Ali Restrepo, Marcos I. TI Understanding the Concept of Health Care-Associated Pneumonia in Lung Transplant Recipients SO CHEST LA English DT Article ID VENTILATOR-ASSOCIATED PNEUMONIA; COMMUNITY-ACQUIRED PNEUMONIA; SINGLE-CENTER EXPERIENCE; EPIDEMIOLOGY; INFECTIONS; MORTALITY; BACTERIA; OUTCOMES; THERAPY AB BACKGROUND: Limited data are available regarding the etiologic impact of health care-associated pneumonia (HCAP) in lung transplant recipients. Therefore, our aim was to evaluate the microbiologic differences between HCAP and hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) in lung transplant recipients with a radiographically confirmed diagnosis of pneumonia. METHODS: We performed a retrospective cohort study of lung transplant recipients with pneumonia at one transplant center over a 7-year period. Eligible patients included lung transplant recipients who developed a first episode of radiographically confirmed pneumonia >= 48 h following transplantation. HCAP, HAP, and VAP were classified according to the American Thoracic Society/Infectious Diseases Society of America 2005 guidelines. chi(2) and Student t tests were used to compare categorical and continuous variables, respectively. RESULTS: Sixty-eight lung transplant recipients developed at least one episode of pneumonia. HCAP (n = 42; 62%) was most common, followed by HAP/VAP (n = 26; 38%) stratified in HAP (n = 20; 77%) and VAP (n = 6; 23%). Pseudomonas aeruginosa was the predominantly isolated organism (n = 22; 32%), whereas invasive aspergillosis was uncommon (< 10%). Multiple-drug resistant (MDR) pathogens were less frequently isolated in patients with HCAP compared with HAP/VAP (5% vs 27%; P = .009). Opportunistic pathogens were less frequently identified in lung transplant recipients with HCAP than in those with HAP/VAP (7% vs 27%; P = .02). Lung transplant recipients with HCAP had a similar mortality at 90 days (n = 9 [21%] vs n = 4 [15%]; P = .3) compared with patients with HAP/VAP. CONCLUSIONS: HCAP was the most frequent infection in lung transplant recipients. MDR pathogens and opportunistic pathogens were more frequently isolated in HAP/VAP. There were no differences in 30- and 90-day mortality between lung transplant recipients with HCAP and those with HAP/VAP. C1 [Palacio, Federico; Levine, Stephanie M.; Restrepo, Marcos I.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Palacio, Federico; Reyes, Luis F.; Levine, Deborah J.; Angel, Luis F.; Fernandez, Juan F.; Levine, Stephanie M.; Abedi, Ali; Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Sanchez, Juan F.] Scott & White Hlth Care Syst, Temple, TX USA. [Rello, Jordi] Univ Autonoma Barcelona, CIBERES, Vall dHebron Inst Res, Hosp Univ Vall dHebron, E-08193 Barcelona, Spain. [Reyes, Luis F.] Univ La Sabana, Bogota, Colombia. RP Restrepo, MI (reprint author), South Texas Vet Hlth Care Syst, Audrey L Murphy Div, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM restrepom@uthscsa.edu OI Rello, Jordi/0000-0003-0676-6210 FU National Heart, Lung and Blood Institute [K23HL096054] FX Dr Restrepo receives support from the National Heart, Lung and Blood Institute [Award K23HL096054]. NR 20 TC 2 Z9 2 U1 0 U2 4 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD AUG PY 2015 VL 148 IS 2 BP 516 EP 522 DI 10.1378/chest.14-1948 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CO2SA UT WOS:000359005700051 PM 25742187 ER PT J AU Pike, F Murugan, R Keener, C Palevsky, PM Vijayan, A Unruh, M Finkel, K Wen, XY Kellum, JA AF Pike, Francis Murugan, Raghavan Keener, Christopher Palevsky, Paul M. Vijayan, Anitha Unruh, Mark Finkel, Kevin Wen, Xiaoyan Kellum, John A. CA Biol Markers Recovery Kidney TI Biomarker Enhanced Risk Prediction for Adverse Outcomes in Critically Ill Patients Receiving RRT SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE KIDNEY INJURY; CYCLE ARREST BIOMARKERS; URINARY BIOMARKERS; RENAL SUPPORT; VALIDATION; DISEASE AB Background and objectives Higher plasma concentrations of inflammatory and apoptosis markers in critically ill patients receiving RRT are associated with RRT dependence and death. This study objective was to examine whether plasma inflammatory (IL-6, -8, -10, and -18; macrophage migration inhibitory factor) and apoptosis (death receptor-5, tumor necrosis factor receptor I and II) biomarkers augment risk prediction of renal recovery and mortality compared with clinical models. Design, setting, participants, & measurements The Biologic Markers of Recovery for the Kidney study (n=817) was a prospective, nested, observational cohort study conducted as an ancillary to the Veterans Affairs/National Institutes of Health Acute renal failure Trial Network study, a randomized trial of intensive versus less intensive RRT in critically ill patients with AKI conducted between November 2003 and July 2007 at 27 Veterans Affairs- and university-affiliated centers. Primary outcomes of interest were renal recovery and mortality at day 60. Results A parsimonious clinical model consisting of only four variables (age, mean arterial pressure, mechanical ventilation, and bilirubin) predicted renal recovery (area under the receiver-operating characteristic curve [AUROC], 0.73; 95% confidence interval [95% CI], 0.68 to 0.78) and mortality (AUROC, 0.74; 95% CI, 0.69 to 0.78). By contrast, individual biomarkers were only modestly predictive of renal recovery (AUROC range, 0.55-0.63) and mortality (AUROC range, 0.54-0.68). Adding plasma IL-8 to a parsimonious model augmented prediction of recovery (AUROC, 0.76; 95% CI, 0.71 to 0.81; P=0.04) and mortality (AUROC, 0.78; 95% CI, 0.73 to 0.82; P<0.01) compared with the clinical model alone. Conclusions This study suggests that a simple four-variable clinical model with plasma IL-8 had predictive value for renal recovery and mortality. These findings require external validation but could easily be used by clinicians. C1 [Pike, Francis; Murugan, Raghavan; Keener, Christopher; Palevsky, Paul M.; Wen, Xiaoyan; Kellum, John A.] Univ Pittsburgh, Sch Med, Dept Crit Care Med, Ctr Crit Care Nephrol, Pittsburgh, PA 15261 USA. [Pike, Francis; Murugan, Raghavan; Keener, Christopher; Unruh, Mark; Wen, Xiaoyan; Kellum, John A.] Univ Pittsburgh, Sch Med, Dept Crit Care Med, CRISMA Clin Res Invest & Syst Modeling Acute Illn, Pittsburgh, PA 15261 USA. [Pike, Francis; Keener, Christopher] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Palevsky, Paul M.] Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [Vijayan, Anitha] Washington Univ, Div Renal Dis, St Louis, MO USA. [Unruh, Mark] Univ New Mexico, Dept Internal Med, Div Nephrol, Albuquerque, NM 87131 USA. [Finkel, Kevin] Univ Texas Med Sch Houston, Div Renal Dis & Hypertens, Houston, TX USA. RP Kellum, JA (reprint author), Univ Pittsburgh, Ctr Crit Care Nephrol, 604 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM kellumja@ccm.upmc.edu OI Palevsky, Paul/0000-0002-7334-5400 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [Y1-DK-3508]; Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development [530] FX The BioMaRK study was conducted by the BioMaRK investigators and supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The primary data and samples from the parent trial (A Comparison of Intensive vs. Conventional Renal Support in Acute Renal Failure; the ATN study), from which the analyses reported here were performed, were supplied by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development (CSP #530) and by the NIDDK Central Repositories. This manuscript does not necessarily reflect the opinions or views of the ATN study, NIDDK Central Repositories, or the NIDDK. The VA/NIH ATN study was supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development (CSP #530) and by NIDDK by interagency agreement Y1-DK-3508. NR 17 TC 7 Z9 7 U1 0 U2 0 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 2015 VL 10 IS 8 BP 1332 EP 1339 DI 10.2215/CJN.09911014 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA CO5AU UT WOS:000359172800007 PM 26048891 ER PT J AU Yu, MK O'Hare, AM Batten, A Sulc, CA Neely, EL Liu, CF Hebert, PL AF Yu, Margaret K. O'Hare, Ann M. Batten, Adam Sulc, Christine A. Neely, Emily L. Liu, Chuan-Fen Hebert, Paul L. TI Trends in Timing of Dialysis Initiation within Versus Outside the Department of Veterans Affairs SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID RENAL REPLACEMENT THERAPY; PATIENTS STARTING DIALYSIS; HEALTH-CARE-SYSTEM; UNITED-STATES; QUALITY; SURVIVAL; OUTCOMES; DISEASE; MORTALITY; ADULTS AB Background and objectives The secular trend toward dialysis initiation at progressively higher levels of eGFR is not well understood. This study compared temporal trends in eGFR at dialysis initiation within versus outside the Department of Veterans Affairs (VA) the largest non-fee-for-service health system in the United States. Design, setting, participants, & measurements The study used linked data from the US Renal Data System, VA, and Medicare to compare temporal trends in eGFR at dialysis initiation between 2000 and 2009 (n=971,543). Veterans who initiated dialysis within the VA were compared with three groups who initiated dialysis outside the VA: (1) veterans whose dialysis was paid for by the VA, (2) veterans whose dialysis was not paid for by the VA, and (3) nonveterans. Logistic regression was used to estimate average predicted probabilities of dialysis initiation at an eGFR >= 10 ml/min per 1.73 m(2). Results The adjusted probability of starting dialysis at an eGFR:10 ml/min per 1.73 m2 increased over time for all groups but was lower for veterans who started dialysis within the VA (0.31; 95% confidence interval [95% CI], 0.30 to 0.32) than for those starting outside the VA, including veterans whose dialysis was (0.36; 95% CI, 0.35 to 0.38) and was not (0.40; 95% CI, 0.40 to 0.40) paid for by the VA and nonveterans (0.39; 95% CI, 0.39 to 0.39). Differences in eGFR at initiation within versus outside the VA were most pronounced among older patients (P for interaction <0.001) and those with a higher risk of 1-year mortality (P for interaction <0.001). Conclusions Temporal trends in eGFR at dialysis initiation within the VA mirrored those in the wider United States dialysis population, but eGFR at initiation was consistently lowest among those who initiated within the VA. Differences in eGFR at initiation within versus outside the VA were especially pronounced in older patients and those with higher 1-year mortality risk. C1 [Yu, Margaret K.; O'Hare, Ann M.; Batten, Adam; Sulc, Christine A.; Neely, Emily L.; Liu, Chuan-Fen; Hebert, Paul L.] Vet Affairs Puget Sound Hlth Care Syst, Vet Affairs Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. [Yu, Margaret K.; O'Hare, Ann M.] Univ Washington, Sch Publ Hlth, Dept Med, Div Nephrol, Seattle, WA 98195 USA. [Liu, Chuan-Fen; Hebert, Paul L.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Yu, Margaret K.; O'Hare, Ann M.] Kidney Res Inst, Seattle, WA USA. RP Yu, MK (reprint author), 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM mkyu@uw.edu FU US Department of Veterans Affairs, Office of Research and Development, Health Services Research & Development Service [IIR 09-094]; VA Advanced Fellowship Program in Health Services Research and Development; American Kidney Fund's Clinical Scientist in Nephrology Program; VA Health Services Research and Development Service; Centers for Disease Control and Prevention; National Institutes of Health FX This material is based upon work supported by the US Department of Veterans Affairs, Office of Research and Development, Health Services Research & Development Service, grant IIR 09-094 (P.L.H.). M.K.Y. was supported by the VA Advanced Fellowship Program in Health Services Research and Development and the American Kidney Fund's Clinical Scientist in Nephrology Program. A.M.O., C.F.L., and P.L.H. receive research funding from the VA Health Services Research and Development Service. A.M.O. also receives research funding from the Centers for Disease Control and Prevention and the National Institutes of Health and royalties from UpToDate. NR 48 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 2015 VL 10 IS 8 BP 1418 EP 1427 DI 10.2215/CJN.12731214 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA CO5AU UT WOS:000359172800017 PM 26206891 ER PT J AU Mintz, AJ Weinberg, I AF Mintz, Ari J. Weinberg, Ido TI Nonatherosclerotic PAD: Approach to Exertional Pain in the Lower Extremities SO CURRENT CARDIOLOGY REPORTS LA English DT Review DE Peripheral artery disease; Intermittent claudication; Nonatherosclerotic peripheral artery disease ID EXTERNAL ILIAC ARTERY; CYSTIC ADVENTITIAL DISEASE; GIANT-CELL ARTERITIS; POPLITEAL VASCULAR ENTRAPMENT; CHRONIC COMPARTMENT SYNDROME; OBLITERANS BUERGERS-DISEASE; RHEUMATOLOGY 1990 CRITERIA; LARGE-VESSEL VASCULITIS; FIBROMUSCULAR DYSPLASIA; TAKAYASU ARTERITIS AB Atherosclerotic peripheral artery disease is the most common cause of intermittent claudication. Nonatherosclerotic peripheral artery disease is a heterogeneous collection of diseases affecting the extracoronary arteries which is not due to atherosclerosis. These diseases include, but are not limited to, popliteal artery entrapment syndrome, cystic adventitial disease, external iliac endofibrosis, and thromboangiitis obliterans. Due to its relatively low prevalence, nonatherosclerotic peripheral artery disease may be misdiagnosed leading to the mismanagement of potentially treatable conditions. The proper and timely diagnosis of these conditions is paramount to the prevention of adverse outcomes as treatments widely vary. The diagnostic approach to patients presenting with intermittent claudication must take into account both atherosclerotic as well as nonatherosclerotic causes of peripheral artery disease making the differential vital to clinical practice. C1 [Mintz, Ari J.] Lahey Hosp & Med Ctr, Internal Med, Burlington, MA 01805 USA. [Weinberg, Ido] Massachusetts Gen Hosp, Vasc Med, Boston, MA 02114 USA. RP Weinberg, I (reprint author), Massachusetts Gen Hosp, Vasc Med, 55 Fruit St, Boston, MA 02114 USA. EM ari.mintz@lahey.org; iweinberg@partners.org NR 92 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3782 EI 1534-3170 J9 CURR CARDIOL REP JI Curr. Cardiol. Rep. PD AUG PY 2015 VL 17 IS 8 AR 66 DI 10.1007/s11886-015-0622-8 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CO1TD UT WOS:000358937200010 PM 26162862 ER PT J AU Witkin, AS Channick, RN AF Witkin, Alison S. Channick, Richard N. TI Chronic Thromboembolic Pulmonary Hypertension: the End Result of Pulmonary Embolism SO CURRENT CARDIOLOGY REPORTS LA English DT Review DE Pulmonary hypertension; Pulmonary embolism ID INTERNATIONAL PROSPECTIVE REGISTRY; RISK-FACTORS; HIGH PREVALENCE; FOLLOW-UP; ENDARTERECTOMY; THROMBOENDARTERECTOMY; BOSENTAN; DISEASE; CT; ANGIOPLASTY AB Chronic thromboembolic pulmonary hypertension (CTEPH) occurs when a pulmonary embolism fails to undergo complete thrombolysis leading to vascular occlusion and pulmonary hypertension. Despite the fact that CTEPH is a potential consequence of pulmonary embolism, diagnosis requires a high degree of vigilance as many patients will not have a history of thromboembolic disease. The ventilation perfusion scan is used to evaluate for the possibility of CTEPH although right heart catheterization and pulmonary artery angiogram are needed to confirm the diagnosis. Pulmonary thromboendarterectomy is the first-line treatment for patients who are surgical candidates. Recently, riociguat has been approved for patients with nonsurgical disease or residual pulmonary hypertension despite surgical intervention. This review describes the pathophysiology, risk factors, diagnosis, and management of CTEPH. C1 [Witkin, Alison S.; Channick, Richard N.] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA. RP Witkin, AS (reprint author), Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Bulfinch 148, Boston, MA 02114 USA. EM aswitkin@partners.org; rchannick@partners.org FU Bayer Pharmaceuticals; Actelion Pharmaceuticals; United Therapeutics Corporation FX Alison S. Witkin declares that she has no conflict of interest. Richard N. Channick has been a consultant and received research grants from Bayer Pharmaceuticals, Actelion Pharmaceuticals, and United Therapeutics Corporation. NR 64 TC 3 Z9 3 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3782 EI 1534-3170 J9 CURR CARDIOL REP JI Curr. Cardiol. Rep. PD AUG PY 2015 VL 17 IS 8 AR 63 DI 10.1007/s11886-015-0621-9 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CO1TD UT WOS:000358937200009 PM 26099554 ER PT J AU Lim, DA AF Lim, Daniel A. TI Transcriptional and epigenetic insights from stem cells and developing tissues SO DEVELOPMENT LA English DT Review DE Developing tissues; Epigenetic regulation; Single cells; Stem cells; Transcriptional regulation; Transdifferentiation ID PLURIPOTENT CELLS; SUPER-ENHANCERS; IDENTITY GENES; SOMATIC-CELLS; GENOME; FATE; HETEROGENEITY; INDUCTION; DISTINCT; DNMT3A AB In March 2015, over 200 scientists gathered in Steamboat Springs, Colorado, USA, for the Keystone Symposium 'Transcriptional and Epigenetic Influences on Stem Cell States' to discuss the molecular mechanisms of pluripotency, cell differentiation, cell reprogramming and transdifferentiation, among other topics. In this meeting, translational research on stem cells for disease modeling and therapy was also presented. This Meeting Review describes key themes and selected findings, providing a timely update on this fast-moving area of research. C1 Univ Calif San Francisco, Dept Neurol Surg, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. RP Lim, DA (reprint author), Univ Calif San Francisco, Dept Neurol Surg, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. EM limd@neurosurg.ucsf.edu NR 31 TC 0 Z9 0 U1 1 U2 12 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 EI 1477-9129 J9 DEVELOPMENT JI Development PD AUG 1 PY 2015 VL 142 IS 15 BP 2549 EP 2553 DI 10.1242/dev.122424 PG 5 WC Developmental Biology SC Developmental Biology GA CO1VF UT WOS:000358943200002 PM 26243867 ER PT J AU Schrauwen, P Lichtenbelt, WDV Spiegelman, BM AF Schrauwen, Patrick Lichtenbelt, Wouter D. van Marken Spiegelman, Bruce M. TI The future of brown adipose tissues in the treatment of type 2 diabetes SO DIABETOLOGIA LA English DT Article DE Brown adipose tissue; Cold-induced thermogenesis; Diabetes; Energy turnover ID ENERGY-EXPENDITURE; COLD-EXPOSURE; ADULT HUMANS; ABLATION; MICE AB The recent recognition that humans possess active depots of brown adipose tissue has boosted the interest in this tissue as a potential target for the prevention and treatment of obesity and related metabolic disorders. Furthermore, it was also revealed that brown adipose tissue (BAT) in humans may consist of so-called beige or brite adipocytes. So far, cold exposure is recognised as the strongest activator of BAT in humans, but there is much ongoing research focused on finding alternative activators of BAT. The consequences of long-term BAT activation and/or cold exposure on metabolic health are still unknown, and this represents an area of intensive research. C1 [Schrauwen, Patrick; Lichtenbelt, Wouter D. van Marken] Maastricht Univ, Med Ctr, NUTRIM Sch Nutr & Translat Res Metab, Dept Human Biol & Human Movement Sci, NL-6200 MD Maastricht, Netherlands. [Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. RP Schrauwen, P (reprint author), Maastricht Univ, Med Ctr, NUTRIM Sch Nutr & Translat Res Metab, Dept Human Biol & Human Movement Sci, POB 616, NL-6200 MD Maastricht, Netherlands. EM p.schrauwen@maastrichtuniversity.nl OI schrauwen, patrick/0000-0002-0973-847X NR 17 TC 12 Z9 12 U1 0 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2015 VL 58 IS 8 BP 1704 EP 1707 DI 10.1007/s00125-015-3611-y PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CO0XN UT WOS:000358877300005 PM 25957230 ER PT J AU Kahn, SE Buse, JB AF Kahn, Steven E. Buse, John B. TI Medications for type 2 diabetes: how will we be treating patients in 50 years? SO DIABETOLOGIA LA English DT Article DE Basal insulin; Beta cell; Diabetes prevention; DPP-4 inhibitors; GLP-1 receptor agonists; Metformin; Pragmatic clinical trials; SGLT2 inhibitors; Stem cell therapy; Sulfonylureas; Thiazolidinediones ID REDUCTION; DESIGN; TRIAL; CARE AB The past 50 years have seen the development of many new options for treating and preventing type 2 diabetes. Despite this success, the individual and societal burden of the disease continues unabated. Thus, the next 50 years will be critical if we are going to quell the major non-communicable disease of our time. The knowledge we will gain in the next few years from clinical studies will inform treatment guidelines with regard to which agents to use in whom and whether more aggressive approaches can slow the development of hyperglycaemia in those at high risk. Beyond that, we anticipate identification of novel targets and techniques for therapeutic intervention. These advances will lead to more personalised approaches to treatment. Most importantly, we will need to focus our political and economic efforts on enhancing and implementing public health approaches aimed at prevention of diabetes and its co-morbidities. This is one of a series of commentaries under the banner '50 years forward', giving personal opinions on future perspectives in diabetes, to celebrate the 50th anniversary of Diabetologia (1965-2015). C1 [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA 98108 USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Buse, John B.] Univ N Carolina, Sch Med, Dept Med, Div Endocrinol & Metab, Chapel Hill, NC USA. RP Kahn, SE (reprint author), VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Dept Med, 1660 S Columbian Way, Seattle, WA 98108 USA. EM skahn@uw.edu OI Kahn, Steven/0000-0001-7307-9002 FU NCATS NIH HHS [1UL1TR001111, UL1 TR001111]; NIDDK NIH HHS [5P30DK017047, P30 DK017047] NR 15 TC 3 Z9 3 U1 1 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2015 VL 58 IS 8 BP 1735 EP 1739 DI 10.1007/s00125-015-3541-8 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CO0XN UT WOS:000358877300011 PM 25773402 ER PT J AU McCaffery, JM Anderson, A Bantle, JP Berkowitz, RI Bray, GA Cheskin, L Clark, JM Curtis, JM Delahanty, LM Evans, M Foreyt, JP Glasser, S Gregg, EW Hanson, RL Hazuda, HP Hill, JO Horton, ES Huggins, GS Jakicic, JM Jeffery, RW Johnson, KC Kahn, SE Kelley, DE Kitabchi, AE Knowler, WC Lewis, CE Montez, MG Kure, A Nathan, DM Nyenwe, E Pajewski, NM Papandonatos, GD Patricio, J Peter, I Peters, A Pi-Sunyer, X Pownall, H Wadden, TA Wagenknecht, LE Wing, RR Wyatt, H AF McCaffery, Jeanne M. Anderson, Andrea Bantle, John P. Berkowitz, Robert I. Bray, George A. Cheskin, Lawrence Clark, Jeanne M. Curtis, Jeffrey M. Delahanty, Linda M. Evans, Mary Foreyt, John P. Glasser, Stephen Gregg, Edward W. Hanson, Robert L. Hazuda, Helen P. Hill, James O. Horton, Edward S. Huggins, Gordon S. Jakicic, John M. Jeffery, Robert W. Johnson, Karen C. Kahn, Steven E. Kelley, David E. Kitabchi, Abbas E. Knowler, William C. Lewis, Cora E. Montez, Maria G. Kure, Anne Nathan, David M. Nyenwe, Ebenezer Pajewski, Nicholas M. Papandonatos, George D. Patricio, Jennifer Peter, Inga Peters, Anne Pi-Sunyer, Xavier Pownall, Henry Wadden, Thomas A. Wagenknecht, Lynne E. Wing, Rena R. Wyatt, Holly CA Look AHEAD Res Grp TI Prospective association of a genetic risk score and lifestyle intervention with cardiovascular morbidity and mortality among individuals with type 2 diabetes: the Look AHEAD randomised controlled trial SO DIABETOLOGIA LA English DT Article DE Cardiovascular disease; Genetics; Lifestyle intervention; Myocardial infarction; Obesity; Stroke; Type 2 diabetes; Weight loss ID CORONARY-HEART-DISEASE; UNRELATED INDIVIDUALS; CLINICAL-TRIAL; WEIGHT-LOSS; WIDE ASSOCIATION; HEALTH; PREDICTION; ATHEROSCLEROSIS; INFERENCE; OBESITY AB Aims/hypothesis Both obesity and genetics contribute to cardiovascular disease (CVD). We examined whether a genetic risk score (GRS) prospectively predicted cardiovascular morbidity andmortality among overweight/obese individuals with type 2 diabetes and whether behavioural weight loss could diminish this association. Methods Look AHEAD (Action for Health in Diabetes) is a randomised controlled trial to determine the effects of intensive lifestyle intervention (ILI), including weight loss and physical activity, relative to diabetes support and education, on cardiovascular outcomes among overweight/obese individuals with type 2 diabetes. Of the participants, 4,016 provided consent for genetic analyses and had DNA samples passing quality control procedures. These secondary data analyses focused on whether a GRS derived from 153 single nucleotide polymorphisms (SNPs) associated with coronary artery disease in the most recent genome-wide association study predicted cardiovascular morbidity and mortality over a median of 9.6 years of follow-up, and whether ILI would diminish this association. Results The GRS significantly predicted the primary composite endpoint of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalisation for angina in the full sample (HR, 95% CI per 1 SD increase in GRS: 1.19 [1.10, 1.28]) and among individuals with no known history of CVD at baseline (HR 1.18 [95% CI 1.07, 1.30]). In no case did ILI significantly alter this association. Conclusions/interpretation A GRS comprised of SNPs significantly predicts cardiovascular morbidity and mortality over 9.6 years of follow-up in Look AHEAD. Lifestyle intervention did not alter the genetic association. C1 [McCaffery, Jeanne M.; Wing, Rena R.] Brown Univ, Alpert Sch Med, Miriam Hosp, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Anderson, Andrea; Pajewski, Nicholas M.] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Bantle, John P.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Berkowitz, Robert I.; Wadden, Thomas A.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Bray, George A.] Louisiana State Univ, Pennington Biomed Res Ctr, Dept Clin Obes, Baton Rouge, LA 70808 USA. [Cheskin, Lawrence] Johns Hopkins, Johns Hopkins Bloomberg Sch Publ Hlth, Global Obes Prevent Ctr, Hlth Behav & Soc, Baltimore, MD USA. [Clark, Jeanne M.] Johns Hopkins Univ, Dept Med Gen Internal Med & Epidemiol, Baltimore, MD USA. [Curtis, Jeffrey M.] St Josephs Hosp, Dept Family Med, Phoenix, AZ USA. [Curtis, Jeffrey M.] NIDDK, Southwest Amer Indian Ctr, NIH, Phoenix, AZ USA. [Delahanty, Linda M.] Massachusetts Gen Hosp, Dept Med, Ctr Diabet, Boston, MA 02114 USA. [Delahanty, Linda M.; Nathan, David M.] Harvard Univ, Sch Med, Boston, MA USA. [Evans, Mary] NIDDK, Dept Digest Dis & Nutr, Bethesda, MD 20892 USA. [Foreyt, John P.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Glasser, Stephen] Univ Alabama Birmingham, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA. [Gregg, Edward W.] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. [Hanson, Robert L.] NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA. [Hazuda, Helen P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. [Hill, James O.] Univ Colorado, Anschutz Hlth & Wellness Ctr, Aurora, CO USA. [Horton, Edward S.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Horton, Edward S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Huggins, Gordon S.] Tufts Med Ctr, MCRI Ctr Translat Genom, Boston, MA USA. [Jakicic, John M.] Univ Pittsburgh, Dept Hlth & Phys Act, Pittsburgh, PA USA. [Jeffery, Robert W.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Johnson, Karen C.] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Kahn, Steven E.; Kure, Anne] Univ Washington, Seattle, WA 98195 USA. [Kelley, David E.] Univ Pittsburgh, Dept Hlth & Phys Act, Pittsburgh, PA USA. [Kitabchi, Abbas E.] Univ Tennessee, Ctr Hlth Sci, Dept Med, Memphis, TN 38163 USA. [Knowler, William C.] NIDDK, Phoenix, AZ USA. [Lewis, Cora E.] Univ Alabama Birmingham, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA. [Montez, Maria G.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. [Kure, Anne] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Nathan, David M.] Massachusetts Gen Hosp, Dept Med, Diabet Unit, Ctr Diabet, Boston, MA 02114 USA. [Nyenwe, Ebenezer] Univ Tennessee, Ctr Hlth Sci, Div Endocrinol Diabet & Metab, Memphis, TN 38163 USA. [Papandonatos, George D.] Brown Univ, Sch Publ Hlth, Dept Biostat, Providence, RI 02912 USA. [Patricio, Jennifer; Pi-Sunyer, Xavier] Columbia Univ, St Lukes Roosevelt Hosp Ctr, New York Obes Res Ctr, New York, NY USA. [Peter, Inga] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Peters, Anne] Roybal Comprehens Hlth Ctr, Los Angeles, CA USA. [Pownall, Henry] Methodist Hosp, Res Inst, Dept Cardiol, Houston, TX 77030 USA. [Wagenknecht, Lynne E.] Wake Forest Sch Med, Dept Publ Hlth Serv, Winston Salem, NC USA. [Wyatt, Holly] Univ Colorado, Anschutz Hlth & Wellness Ctr, Aurora, CO USA. RP McCaffery, JM (reprint author), Miriam Hosp, Weight Control & Diabet Res Ctr, 196 Richmond St, Providence, RI 02903 USA. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases [DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, DK56992]; National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; NIH Office of Research on Women's Health; Centers for Disease Control and Prevention; Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases; Johns Hopkins Medical Institutions Bayview General Clinical Research Center [M01RR02719]; Massachusetts General Hospital Mallinckrodt General Clinical Research Center; Massachusetts Institute of Technology General Clinical Research Center [M01RR01066]; University of Colorado Health Sciences Center General Cl inical Research Center [M01RR00051]; Clinical Nutrition Research Unit [P30 DK48520]; University of Tennessee at Memphis General Clinical Research Center [M01RR0021140]; University of Pittsburgh General Clinical Research Center (GCRC) [M01RR000056]; Clinical Translational Research Center (CTRC) - Clinical and Translational Science Award [UL1 RR 024153]; NIH grant [DK 046204]; VA Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs; Frederic C. Bartter General Clinical Research Center [M01RR01346] FX Funded by the National Institutes of Health through cooperative agreements with the National Institute of Diabetes and Digestive and Kidney Diseases: DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135 and DK56992. Additional funding was provided by the National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; NIH Office of Research on Women's Health; and the Centers for Disease Control and Prevention. This research was supported in part by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. The Indian Health Service (I.H.S.) provided personnel, medical oversight and use of facilities. The opinions expressed in this paper are those of the authors and do not necessarily reflect the views of the I.H.S. or other funding sources.; Additional support was received from The Johns Hopkins Medical Institutions Bayview General Clinical Research Center (M01RR02719); the Massachusetts General Hospital Mallinckrodt General Clinical Research Center and the Massachusetts Institute of Technology General Clinical Research Center (M01RR01066); the University of Colorado Health Sciences Center General Cl inical Research Center (M01RR00051) and Clinical Nutrition Research Unit (P30 DK48520); the University of Tennessee at Memphis General Clinical Research Center (M01RR0021140); the University of Pittsburgh General Clinical Research Center (GCRC) (M01RR000056); the Clinical Translational Research Center (CTRC) funded by the Clinical and Translational Science Award (UL1 RR 024153) and NIH grant (DK 046204); the VA Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs; and the Frederic C. Bartter General Clinical Research Center (M01RR01346). NR 35 TC 1 Z9 1 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2015 VL 58 IS 8 BP 1803 EP 1813 DI 10.1007/s00125-015-3610-z PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CO0XN UT WOS:000358877300020 ER PT J AU Bergman, BG Hoeppner, BB Nelson, LM Slaymaker, V Kelly, JF AF Bergman, Brandon G. Hoeppner, Bettina B. Nelson, Lindsay M. Slaymaker, Valerie Kelly, John F. TI The effects of continuing care on emerging adult outcomes following residential addiction treatment SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Substance use disorders; Emerging adulthood; Continuing care; 12-Step mutual-help organizations ID SUBSTANCE-USE DISORDERS; COCAINE-DEPENDENT PATIENTS; RANDOMIZED CLINICAL-TRIAL; DRUG-TREATMENT; YOUNG-ADULTS; SELF-HELP; ABUSE TREATMENT; OUTPATIENT TREATMENT; TREATMENT RETENTION; MEDIATION ANALYSIS AB Background: Professional continuing care services enhance recovery rates among adults and adolescents, though less is known about emerging adults (18-25 years old). Despite benefit shown from emerging adults' participation in 12-step mutual-help organizations (MHOs), it is unclear whether participation offers benefit independent of professional continuing care services. Greater knowledge in this area would inform clinical referral and linkage efforts. Methods: Emerging adults (N=284; 74% male; 95% Caucasian) were assessed during the year after residential treatment on outpatient sessions per week, percent days in residential treatment and residing in a sober living environment, substance use disorder (SUD) medication use, active 12-step MHO involvement (e.g., having a sponsor, completing step work, contact with members outside meetings), and continuous abstinence (dichotomized yes/no). One generalized estimating equation (GEE) model tested the unique effect of each professional service on abstinence, and, in a separate GEE model, the unique effect of 12-step MHO involvement on abstinence over and above professional services, independent of individual covariates. Results: Apart from SUD medication, all professional continuing care services were significantly associated with abstinence over and above individual factors. In the more comprehensive model, relative to zero 12-step MHO activities, odds of abstinence were 1.3 times greater if patients were involved in one activity, and 3.2 times greater if involved in five activities (lowest mean number of activities in the sample across all follow-ups). Conclusions: Both active involvement in 12-step MHOs and recovery-supportive, professional services that link patients with these community-based resources may enhance outcomes for emerging adults after residential treatment. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Bergman, Brandon G.; Hoeppner, Bettina B.; Kelly, John F.] Massachusetts Gen Hosp, Boston, MA 02113 USA. [Bergman, Brandon G.; Hoeppner, Bettina B.; Kelly, John F.] Harvard Univ, Sch Med, Boston, MA USA. [Nelson, Lindsay M.; Slaymaker, Valerie] Hazelden Betty Ford Fdn Butler Ctr Res, Center City, MN USA. RP Bergman, BG (reprint author), Massachusetts Gen Hosp, Recovery Res Inst, 151 Merrimac St,Suite 620, Boston, MA 02113 USA. EM bgbergman@mgh.harvard.edu FU NIDA [K01DA027097]; NIAAA [1R21AA018185-01A2] FX This work was funded by 1R21AA018185-01A2 and by an anonymous donation for youth research to the Hazelden Foundation. Dr. Hoeppner's participation is supported by NIDA grant K01DA027097. Dr. Kelly's participation is supported by NIAAA grant 1R21AA018185-01A2. NR 82 TC 2 Z9 2 U1 2 U2 11 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD AUG 1 PY 2015 VL 153 BP 207 EP 214 DI 10.1016/j.drugalcdep.2015.05.017 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA CO5AP UT WOS:000359172300031 PM 26116368 ER PT J AU Tsui, JI Lira, MC Cheng, DM Winter, MR Alford, DP Liebschutz, JM Mao, JR Edwards, RR Samet, JH AF Tsui, Judith I. Lira, Marlene C. Cheng, Debbie M. Winter, Michael R. Alford, Daniel P. Liebschutz, Jane M. Mao, Jianren Edwards, Robert R. Samet, Jeffrey H. TI Hepatitis C virus infection and pain sensitivity in patients on methadone or buprenorphine maintenance therapy for opioid use disorders SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Opioid-related disorders; Pain; Chronic pain; Hyperalgesia; Hepatitis C; HIV ID NECROSIS-FACTOR-ALPHA; SUBSTANCE USE; GLOBAL EPIDEMIOLOGY; DEPENDENT PATIENTS; CLINICAL-TRIALS; PERSISTENT PAIN; INJECT DRUGS; HEALTH-CARE; PREVALENCE; INTERLEUKIN-6 AB Background: Patients with opioid use disorders on opioid agonist therapy (OAT) have lower pain tolerance compared to controls. While chronic viral infections such as HCV and HIV have been associated with chronic pain in this population, no studies have examined their impact on pain sensitivity. Methods: We recruited 106 adults (41 uninfected controls; 40 HCV mono-infected; and 25 HCV/HIV co-infected) on buprenorphine or methadone to assess whether HCV infection (with or without HIV) was associated with increased experimental pain sensitivity and self-reported pain. The primary outcome was cold pain tolerance assessed by cold-pressor test. Secondary outcomes were cold pain thresholds, wind-up ratios to repetitive mechanical stimulation (i.e., temporal summation) and acute and chronic pain. Multivariable regression models evaluated associations between viral infection status and outcomes, adjusting for other factors. Results: No significant differences were detected across groups for primary or secondary outcomes. Adjusted mean cold pain tolerance was 25.7 (uninfected controls) vs. 26.8 (HCV mono-infection) vs. 25.3 (HCV/HIV co-infection) seconds (global p-value = 0.93). Current pain appeared more prevalent among HCV mono-infected (93%) compared to HCV/HIV co-infected participants (76%) and uninfected controls (80%), as did chronic pain (77% vs. 64% vs. 61%, respectively). However, differences were not statistically significant in multivariable models. Conclusion: This study did not detect an association between HCV infection and increased sensitivity to pain among adults with and without HIV who were treated with buprenorphine or methadone for opioid use disorders. Results reinforce that pain and hyperalgesia are common problems in this population. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Tsui, Judith I.] Univ Washington, Sch Med, Dept Med, Gen Internal Med Sect, Seattle, WA 98104 USA. [Lira, Marlene C.; Alford, Daniel P.; Liebschutz, Jane M.; Samet, Jeffrey H.] Boston Med Ctr, Gen Internal Med Sect, Dept Med, Clin Addict Res & Educ Unit, Boston, MA 02118 USA. [Cheng, Debbie M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Winter, Michael R.] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA 02118 USA. [Alford, Daniel P.; Liebschutz, Jane M.; Samet, Jeffrey H.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Mao, Jianren] Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02110 USA. [Edwards, Robert R.] Brigham & Womens Hosp, Dept Anesthesia, Pain Management Ctr, Chestnut Hill, MA 02467 USA. [Samet, Jeffrey H.] Boston Univ, Dept Community Hlth Sci, Sch Publ Hlth, Boston, MA 02118 USA. RP Tsui, JI (reprint author), Univ Washington, Sch Med, Dept Med, Gen Internal Med Sect, 325 9th Ave, Seattle, WA 98104 USA. EM tsuij@uw.edu FU National Institute on Drug Abuse [K23DA027367]; BU-CTSI [KL2 TR000158] FX This study was supported by grant K23DA027367 from the National Institute on Drug Abuse, and through BU-CTSI Grant number KL2 TR000158. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Drug Abuse or the National Institutes of Health. NR 58 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD AUG 1 PY 2015 VL 153 BP 286 EP 292 DI 10.1016/j.drugalcdep.2015.05.011 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA CO5AP UT WOS:000359172300042 PM 26048638 ER PT J AU Christodoulides, N De La Garza, R Simmons, GW McRae, MP Wong, J Newton, TF Smith, R Mahoney, JJ Hohenstein, J Gomez, S Floriano, PN Talavera, H Sloan, DJ Moody, DE Andrenyak, DM Kosten, TR Haque, A McDevitt, JT AF Christodoulides, Nicolaos De La Garza, Richard, II Simmons, Glennon W. McRae, Michael P. Wong, Jorge Newton, Thomas F. Smith, Regina Mahoney, James J., III Hohenstein, Justin Gomez, Sobeyda Floriano, Pierre N. Talavera, Humberto Sloan, Daniel J. Moody, David E. Andrenyak, David M. Kosten, Thomas R. Haque, Ahmed McDevitt, John T. TI Application of programmable bio-nano-chip system for the quantitative detection of drugs of abuse in oral fluids SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Drugs of abuse; Programmable bio-nano-chip; Oral fluid; Multiplexed; On-site testing ID TANDEM MASS-SPECTROMETRY; POINT-OF-CARE; TESTING DEVICES; COCAINE; DIAGNOSTICS; PERFORMANCE; METABOLITES; MICROCHIP; PLASMA; FUTURE AB Objective: There is currently a gap in on-site drug of abuse monitoring. Current detection methods involve invasive sampling of blood and urine specimens, or collection of oral fluid, followed by qualitative screening tests using immunochromatographic cartridges. While remote laboratories then may provide confirmation and quantitative assessment of a presumptive positive, this instrumentation is expensive and decoupled from the initial sampling making the current drug-screening program inefficient and costly. The authors applied a noninvasive oral fluid sampling approach integrated with the in-development chip-based Programmable bio-nano-chip (p-BNC) platform for the detection of drugs of abuse. Method: The p-BNC assay methodology was applied for the detection of tetrahydrocannabinol, morphine, amphetamine, methamphetamine, cocaine, methadone and benzodiazepines, initially using spiked buffered samples and, ultimately, using oral fluid specimen collected from consented volunteers. Results: Rapid (similar to 10 min), sensitive detection (similar to ng/mL) and quantitation of 12 drugs of abuse was demonstrated on the p-BNC platform. Furthermore, the system provided visibility to time-course of select drug and metabolite profiles in oral fluids; for the drug cocaine, three regions of slope were observed that, when combined with concentration measurements from this and prior impairment studies, information about cocaine-induced impairment may be revealed. Conclusions: This chip-based p-BNC detection modality has significant potential to be used in the future by law enforcement officers for roadside drug testing and to serve a variety of other settings, including outpatient and inpatient drug rehabilitation centers, emergency rooms, prisons, schools, and in the workplace. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Christodoulides, Nicolaos; Simmons, Glennon W.; McRae, Michael P.; Wong, Jorge; Smith, Regina; Hohenstein, Justin; Gomez, Sobeyda; Floriano, Pierre N.; Talavera, Humberto; Sloan, Daniel J.; Haque, Ahmed; McDevitt, John T.] Rice Univ, Dept Bioengn, Houston, TX USA. [Christodoulides, Nicolaos; Simmons, Glennon W.; Wong, Jorge; Floriano, Pierre N.; McDevitt, John T.] Rice Univ, Dept Chem, Houston, TX USA. [De La Garza, Richard, II; Newton, Thomas F.; Mahoney, James J., III; Kosten, Thomas R.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [De La Garza, Richard, II; Newton, Thomas F.; Kosten, Thomas R.] Baylor Coll Med, Dept Pharmacol, Houston, TX 77030 USA. [De La Garza, Richard, II; Kosten, Thomas R.] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. [Newton, Thomas F.; Kosten, Thomas R.] Dept Vet Affairs Med Ctr, Houston, TX USA. [Moody, David E.; Andrenyak, David M.] Univ Utah, Dept Pharmacol & Toxicol, Ctr Human Toxicol, Salt Lake City, UT 84112 USA. [McDevitt, John T.] NYU, Dept Biomat, Bioengn Inst, New York, NY 10010 USA. RP McDevitt, JT (reprint author), NYU, Dept Biomat, Bioengn Inst, 433 First Ave,Room 820, New York, NY 10010 USA. EM mcdevitt@nyu.edu RI Mahoney, James/I-2753-2014; McDevitt, John/P-4108-2014; OI Mahoney, James/0000-0003-0824-1776; McDevitt, John/0000-0001-8789-9351; newton, thomas/0000-0002-3198-5901 FU United Kingdom (UK) Home Office Center of Applied Science and Technology (CAST) [PO7165721]; NIH through the National Institute of Dental and Craniofacial Research [5U01 DE017793] FX Funding support for this work was provided by the United Kingdom (UK) Home Office Center of Applied Science and Technology (CAST) (PO7165721). This sponsor was involved in the design of the study and contributed suggestions on the interpretation of data and definition of the next steps. Support for the p-BNC core instrumentation work was provided also by the (NIH) through the National Institute of Dental and Craniofacial Research (award number 5U01 DE017793). NR 36 TC 7 Z9 7 U1 3 U2 27 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD AUG 1 PY 2015 VL 153 BP 306 EP 313 DI 10.1016/j.drugalcdep.2015.04.026 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA CO5AP UT WOS:000359172300045 PM 26048639 ER PT J AU Niquet, J Baldwin, R Gezalian, M Wasterlain, CG AF Niquet, Jerome Baldwin, Roger Gezalian, Michael Wasterlain, Claude G. TI Deep hypothermia for the treatment of refractory status epilepticus SO EPILEPSY & BEHAVIOR LA English DT Article DE Status epilepticus; Hypothermia; EEG power ID TRAUMATIC BRAIN-INJURY; SUSTAINING STATUS EPILEPTICUS; CIRCULATORY ARREST TRIAL; THERAPEUTIC HYPOTHERMIA; NEONATAL ENCEPHALOPATHY; BARRIER PERMEABILITY; MODERATE HYPOTHERMIA; MILD HYPOTHERMIA; PROFOUND HYPOTHERMIA; MEMBRANE-PROPERTIES AB In a rat model of status epilepticus (SE) induced by lithium and pilocarpine and refractory to midazolam, deep hypothermia (20 "C for 30 min) reduced EEG power over 50-fold, stopped SE within 12 min, and reduced EEG spikes by 87%. Hypothermia deserves further investigation as a treatment of last resort for refractory SE. Published by Elsevier Inc. C1 [Niquet, Jerome; Wasterlain, Claude G.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Niquet, Jerome; Baldwin, Roger; Gezalian, Michael; Wasterlain, Claude G.] Vet Affairs Greater Los Angeles Healthcare Syst, Epilepsy Res Lab 151, Los Angeles, CA USA. [Wasterlain, Claude G.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. RP Niquet, J (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Epilepsy Res Lab, 11301 Wilshire Blvd,Bldg 114,Room 139, West Los Angeles, CA 90073 USA. EM jniquet@ucla.edu OI Niquet, Jerome/0000-0002-1005-0517; Wasterlain, Claude/0000-0002-2100-9114 FU VHA Research Service; NINDS [UO1 NS074926] FX This study was supported by VHA Research Service (CW) and NINDS (grant UO1 NS074926, CW). NR 69 TC 2 Z9 2 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 1525-5050 EI 1525-5069 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD AUG PY 2015 VL 49 BP 313 EP 317 DI 10.1016/j.yebeh.2015.06.028 PG 5 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA CO7CK UT WOS:000359314900058 PM 26198217 ER PT J AU Bollerslev, J Rejnmark, L Marcocci, C Shoback, DM Sitges-Serra, A van Biesen, W Dekkers, OM AF Bollerslev, Jens Rejnmark, Lars Marcocci, Claudio Shoback, Dolores M. Sitges-Serra, Antonio van Biesen, Wim Dekkers, Olaf M. TI European Society of Endocrinology Clinical Guideline: Treatment of chronic hypoparathyroidism in adults SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID CALCIUM-SENSING RECEPTOR; QUALITY-OF-LIFE; CONGENITAL HYPERPARATHYROIDISM SECONDARY; PARATHYROID-HORMONE SECRETION; VITAMIN-D DEFICIENCY; SERUM-CALCIUM; MATERNAL HYPOPARATHYROIDISM; TOTAL THYROIDECTOMY; BONE METABOLISM; URINARY CALCIUM AB Hypoparathyroidism (HypoPT) is a rare (orphan) endocrine disease with low calcium and inappropriately low (insufficient) circulating parathyroid hormone levels, most often in adults secondary to thyroid surgery. Standard treatment is activated vitamin D analogues and calcium supplementation and not replacement of the lacking hormone, as in other hormonal deficiency states. The purpose of this guideline is to provide clinicians with guidance on the treatment and monitoring of chronic HypoPT in adults who do not have end-stage renal disease. We intend to draft a practical guideline, focusing on operationalized recommendations deemed to be useful in the daily management of patients. This guideline was developed and solely sponsored by The European Society of Endocrinology, supported by CBO (Dutch Institute for Health Care Improvement) and based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) principles as a methodological base. The clinical question on which the systematic literature search was based and for which available evidence was synthesized was: what is the best treatment for adult patients with chronic HypoPT? This systematic search found 1100 articles, which was reduced to 312 based on title and abstract. The working group assessed these for eligibility in more detail, and 32 full-text articles were assessed. For the final recommendations, other literature was also taken into account. Little evidence is available on how best to treat HypoPT. Data on quality of life and the risk of complications have just started to emerge, and clinical trials on how to optimize therapy are essentially non-existent. Most studies are of limited sample size, hampering firm conclusions. No studies are available relating target calcium levels with clinically relevant endpoints. Hence it is not possible to formulate recommendations based on strict evidence. This guideline is therefore mainly based on how patients are managed in clinical practice, as reported in small case series and based on the experiences of the authors. C1 [Bollerslev, Jens] Oslo Univ Hosp, Med Clin, Sect Specialized Endocrinol, Oslo, Norway. [Bollerslev, Jens] Univ Oslo, Fac Med, Oslo, Norway. [Rejnmark, Lars] Aarhus Univ Hosp, Dept Endocrinol & Internal Med, DK-8000 Aarhus, Denmark. [Marcocci, Claudio] Univ Pisa, Dept Clin & Expt Med, Pisa, Italy. [Shoback, Dolores M.] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Vet Affairs, Endocrine Res Unit, San Francisco, CA 94143 USA. [Sitges-Serra, Antonio] Hosp Univ Mar, Endocrine Surg Unit, Barcelona, Spain. [van Biesen, Wim] Ghent Univ Hosp, Div Renal, Ghent, Belgium. [Dekkers, Olaf M.] Leiden Univ Med Ctr, Dept Med, Div Endocrinol, Leiden, Netherlands. [Dekkers, Olaf M.] Leiden Univ Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands. [Dekkers, Olaf M.] Aarhus Univ Hosp, Dept Clin Epidemiol, DK-8000 Aarhus, Denmark. RP Bollerslev, J (reprint author), Oslo Univ Hosp, Med Clin, Sect Specialized Endocrinol, Oslo, Norway. EM Jens.bollerslev@medisin.uio.no FU European Society of Endocrinology FX This guideline was sponsored by the European Society of Endocrinology. NR 107 TC 16 Z9 18 U1 2 U2 9 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 EI 1479-683X J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD AUG PY 2015 VL 173 IS 2 BP EG1 EP EG20 DI 10.1530/EJE-15-0628 PG 20 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CO1XH UT WOS:000358949000003 PM 26160136 ER PT J AU Psotka, MA Teerlink, JR AF Psotka, Mitchell A. Teerlink, John R. TI Cardiac myosin activators: up and coming SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Editorial Material ID SYSTOLIC HEART-FAILURE; OMECAMTIV MECARBIL; PHASE-2 TRIAL; MUSCLE; CONTRACTILITY; ATP C1 [Psotka, Mitchell A.; Teerlink, John R.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Teerlink, John R.] San Francisco VA Med Ctr, Cardiol Sect, San Francisco, CA 94121 USA. RP Teerlink, JR (reprint author), San Francisco VA Med Ctr, Cardiol, 111C,Bldg 203,Room 2A-49,4150 Clement St, San Francisco, CA 94121 USA. EM john.teerlink@ucsf.edu NR 15 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD AUG PY 2015 VL 17 IS 8 BP 750 EP 752 DI 10.1002/ejhf.313 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CO3JF UT WOS:000359052400002 PM 26179667 ER PT J AU Jhund, PS Anand, IS Komajda, M Claggett, BL McKelvie, RS Zile, MR Carson, PE McMurray, JJV AF Jhund, Pardeep S. Anand, Inder S. Komajda, Michel Claggett, Brian L. McKelvie, Robert S. Zile, Michael R. Carson, Peter E. McMurray, John J. V. TI Changes in N-terminal pro-B-type natriuretic peptide levels and outcomes in heart failure with preserved ejection fraction: an analysis of the I-Preserve study SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Heart failure; Biological markers; Prognosis; Natriuretic peptide ID VENTRICULAR SYSTOLIC DYSFUNCTION; RANDOMIZED CONTROLLED-TRIAL; PROGNOSTIC VALUE; VAL-HEFT; AMBULATORY PATIENTS; BASE-LINE; SPIRONOLACTONE; NEUROHORMONES; IRBESARTAN; MORTALITY AB AimsIn patients with heart failure (HF) and reduced ejection fraction, decreases or increases in NT-proBNP levels are associated with better and worse outcomes, respectively. The association in HF and preserved ejection fraction (HF-PEF) is unknown. We examined the association between change in level of NT-proBNP and prognosis in patients with HF-PEF. Methods and resultsWe examined the association between change in NT-proBNP from baseline to 6 months and cardiovascular (CV) death or HF hospitalization in 2612 participants in the Irbesartan in Patients with Heart Failure and Preserved Systolic Function Study (I-Preserve). Change in NT-proBNP was modelled as a restricted cubic spline in a Cox model after adjusting for baseline NT-proBNP and known prognostic variables. Median change in NT-proBNP from baseline was -7pg/mL (interquartile range -143 to +108). After adjustment, a 1000pg/mL decrease in NT-proBNP from baseline was associated with a reduction in the risk of CV death or HF hospitalization [hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.53-1.02]; a 1000pg/mL increase was associated with an increase in risk (HR 2.01, 95% CI 1.50-2.69). Beyond a 1000pg/mL rise or fall, there was little additional change in risk. Addition of change in NT-proBNP at 6 months to a model with only baseline NT-proBNP improved the C-statistic from 0.752 to 0.769 (P = 0.013). ConclusionIn HF-PEF, a rise in NT-proBNP was associated with an increase in risk of CV death or HF hospitalization and a fall was associated with a trend towards a decrease in risk. NT-proBNP may be a useful marker to monitor prognosis in this condition. C1 [Jhund, Pardeep S.; McMurray, John J. V.] Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Inst Cardiovasc & Med Sci, Glasgow G12 9QZ, Lanark, Scotland. [Anand, Inder S.] Vet Affairs Med Ctr, Minneapolis, MN USA. [Anand, Inder S.] Univ Minnesota, Minneapolis, MN USA. [Komajda, Michel] Univ Paris 06, Paris, France. [Komajda, Michel] Grp Hosp Pitie Salpetriere, F-75634 Paris, France. [Claggett, Brian L.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [McKelvie, Robert S.] McMaster Univ, Hamilton Hlth Sci, Hamilton, ON, Canada. [Zile, Michael R.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Zile, Michael R.] Med Univ S Carolina, Charleston, SC 29425 USA. [Carson, Peter E.] Georgetown Univ, Washington, DC USA. [Carson, Peter E.] Washington DC Vet Affairs Med Ctr, Washington, DC USA. RP McMurray, JJV (reprint author), Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Inst Cardiovasc & Med Sci, 126 Univ Ave, Glasgow G12 9QZ, Lanark, Scotland. EM John.McMurray@glasgow.ac.uk OI mcmurray, john/0000-0002-6317-3975; Jhund, Pardeep/0000-0003-4306-5317 NR 28 TC 12 Z9 12 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD AUG PY 2015 VL 17 IS 8 BP 809 EP 817 DI 10.1002/ejhf.274 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CO3JF UT WOS:000359052400012 PM 25921853 ER PT J AU Tamers, SL Okechukwu, C Marino, M Gueguen, A Goldberg, M Zins, M AF Tamers, Sara L. Okechukwu, Cassandra Marino, Miguel Gueguen, Alice Goldberg, Marcel Zins, Marie TI Effect of stressful life events on changes in smoking among the French: longitudinal findings from GAZEL SO EUROPEAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID CESSATION; PATTERNS; RELAPSE; COHORT; STYLE; BASE AB Background: Changes in life events may play a contributing role in changes in smoking behaviors. The objective was to examine the impact of stressful life events (SLEs) on smoking among French adults. Methods: We examined smoking prevalence in 20 625 employees of the French GAZEL cohort for up to 5 years before and after a SLE during three time periods (years -1 vs. -5; years +1 vs. -1; years +5 vs. +1). Repeated measures analysis of time series data indexed to events were used, employing generalized estimating equations. Results: For women, comparing 1 year after vs. 1 year before SLEs, decreased odds of smoking were found for employment promotion (OR: 0.80; 95% CI = 0.67-0.95), marriage (OR: 0.57; 95% CI = 0.48-0.68) and divorce (OR: 0.78; 95% CI = 0.68-0.90). Comparing 5 years after to 1 year after SLEs, women had decreased odds of smoking for important purchase (OR: 0.87; 95% CI = 0.79-0.96), children leaving home (OR: 0.83; 95% CI = 0.74-0.93), retirement (OR: 0.73; 95% CI = 0.64-0.83) and death of loved one (OR: 0.86; 95% CI = 0.79-0.93). For men, decreased odds of smoking were observed in all three time periods for all SLEs except when comparing 1 year before to 5 years before marriage (OR: 1.66; 95% CI = 1.09-2.52) and divorce (OR: 1.49; 95% CI = 1.25-1.77). Conclusion: Time surrounding SLEs during which individuals are susceptible to changing smoking behaviors may be an important consideration. C1 [Tamers, Sara L.; Okechukwu, Cassandra] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Tamers, Sara L.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Marino, Miguel] Oregon Hlth & Sci Univ, Dept Family Med, Portland, OR 97201 USA. [Marino, Miguel] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Div Biostat, Portland, OR 97201 USA. [Gueguen, Alice; Goldberg, Marcel; Zins, Marie] Ctr Res Epidemiol & Populat Hlth, INSERM, Epidemiol Occupat & Social Determinants Hlth, U1018, F-94807 Villejuif, France. [Gueguen, Alice; Goldberg, Marcel; Zins, Marie] Univ Versailles St Quentin, UMRS 1018, Versailles, France. RP Tamers, SL (reprint author), NIOSH, Off Total Worker Hlth Coordinat & Res Support, Off Director, Ctr Dis Control & Prevent, 395 E St,SW,Suite 9200, Washington, DC 20201 USA. EM STamers@cdc.gov FU EDF-GDF; l'INSERM; l'Association de la Recherche sur le Cancer; la Fondation de France; le Ministere de la Sante; NIH/NCI Harvard Education Program in Cancer Prevention [R25 CA057713]; NIH/NCI Reducing Social Disparities in Cancer Risk [K05 CA108663-05] FX The authors express their gratitude to the EDF-GDF and acknowledge the invaluable assistance of the GAZEL cohort study team. This research was supported by the EDF-GDF, l'INSERM, l'Association de la Recherche sur le Cancer, la Fondation de France, le Ministere de la Sante, the NIH/NCI Harvard Education Program in Cancer Prevention (R25 CA057713) and the NIH/NCI Reducing Social Disparities in Cancer Risk (K05 CA108663-05). NR 35 TC 2 Z9 2 U1 0 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1101-1262 EI 1464-360X J9 EUR J PUBLIC HEALTH JI Eur. J. Public Health PD AUG PY 2015 VL 25 IS 4 BP 711 EP 715 DI 10.1093/eurpub/ckv036 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CO4VV UT WOS:000359159900033 PM 25762691 ER PT J AU Collins, GT Chen, Y Tschumi, C Rush, EL Mensah, A Koek, W France, CP AF Collins, Gregory T. Chen, Yu Tschumi, Chris Rush, Elise L. Mensah, Ayele Koek, Wouter France, Charles P. TI Effects of Consuming a Diet High in Fat and/or Sugar on the Locomotor Effects of Acute and Repeated Cocaine in Male and Female C57BL/6J Mice SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE high-fat diet; sucrose; cocaine; behavioral sensitization; sex differences ID BEHAVIORAL SENSITIZATION; FOOD-DEPRIVATION; GENE-EXPRESSION; RATS; QUINPIROLE; SUCROSE; OBESITY; CHOW; NEUROPLASTICITY; SENSITIVITY AB Drug abuse and obesity are serious public health problems. Dopamine plays a central role in mediating the reinforcing effects of drugs and food. Prolonged use of drugs is known to alter the function and/or sensitivity of many neurotransmitter systems, including dopamine; however, the impact of consuming foods high in fat and/or sugar is less clear. These studies characterized the locomotor effects of acute and repeated cocaine in male and female C57BL/6J mice consuming 1 of 4 diets: (a) standard chow + water; (b) standard chow + 10% sucrose solution; (c) high-fat chow + water; or (d) high-fat chow + 10% sucrose solution. The acute locomotor effects of cocaine (3.2-32.0 mg/kg) were evaluated 4 weeks after initiating dietary conditions; the effects of repeated cocaine administration were evaluated after 5, 6, 7, and 12 weeks. During acute tests, mice consuming a diet high in fat and/or sucrose exhibited greater locomotor responses to cocaine than mice consuming standard chow and water, regardless of sex. Although diet-induced enhancements persisted across repeated cocaine testing, locomotor sensitization developed more rapidly in females drinking sucrose (and consuming either standard or high-fat chow) than in females consuming standard chow and water. In addition to providing evidence that consuming a diet high in fat and/or sugar enhances abuse-related effects of cocaine in ways that might increase vulnerability to abuse cocaine, these studies identified a potentially important sex-related difference in the interaction between nutrition and cocaine effects, with the impacts of sucrose consumption being greater in females than in males. C1 [Collins, Gregory T.; Chen, Yu; Tschumi, Chris; Rush, Elise L.; Mensah, Ayele; Koek, Wouter; France, Charles P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Collins, Gregory T.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Koek, Wouter; France, Charles P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. RP Collins, GT (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, 7703 Floyd Curl Dr,Mail Code 7764, San Antonio, TX 78229 USA. EM collinsg@uthscsa.edu RI Collins, Gregory/K-3125-2012 FU National Institutes of Health [K05 DA017918]; American Society for Pharmacology and Experimental Therapeutics FX Charles P. France was supported by a grant from the National Institutes of Health (K05 DA017918), and Elise L. Rush was supported by a Summer Undergraduate Research Fellowship through the American Society for Pharmacology and Experimental Therapeutics. These funding sources provided financial support, but had no other role in the design and completion of the studies. All authors contributed in a significant way to the completion of the studies and/or the writing of the manuscript, and all authors have approved the final manuscript. We thank Melson Mesmin for his technical assistance in completing these studies. NR 38 TC 6 Z9 7 U1 1 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1064-1297 EI 1936-2293 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD AUG PY 2015 VL 23 IS 4 BP 228 EP 237 DI 10.1037/pha0000019 PG 10 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA CN9VI UT WOS:000358797800005 PM 26237320 ER PT J AU Shahid, H Singh, JA AF Shahid, Hania Singh, Jasvinder A. TI Investigational drugs for hyperuricemia SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE AC-201; arhalofenate; KX1151; LC350189; lesinurad; levotofisopam; Marine Active; OAT4; purine nucleoside phosphorylase; RDEA; tranilast; ulodesine (BCX-4208); UR1102; urate anion transporter 1 ID NUTRITION EXAMINATION SURVEY; URATE-LOWERING THERAPIES; CHRONIC KIDNEY-DISEASE; URIC-ACID; NATIONAL-HEALTH; GOUT PATIENTS; RISK-FACTORS; GENERAL-POPULATION; COST-EFFECTIVENESS; ADVERSE-REACTIONS AB Introduction: The unmet need and the growing prevalence of hyperuricemia and its complications worldwide have pushed investigators to identify new agents to manage hyperuricemia. Areas covered: This review discusses the drugs in preclinical and early clinical trials for hyperuricemia, their mechanisms of action and available results. This article reviews a total of 10 novel agents: i) drugs in Phase II/III trials - arhalofenate (MBX201), AC201, RDEA group of drugs (including lesinurad), tranilast, ulodesine (BCX4208); and ii) drugs in Phase I trials, including levotofisopam, UR1102, KX1151, LC350189 and Marine Active. Expert opinion: The goal of emerging therapies is to address the unsatisfactory control of serum uric acid in patients with symptomatic hyperuricemia such as those with gout, to provide better tolerability compared to traditional agents and minimize the risk of adverse events, especially in patients with comorbidities and the elderly. Some drugs like arhalofenate, ulodesine (BCX-4208) and lesinurad are in or have completed Phase II and Phase III trials. The growing knowledge about the urate transporters in the kidney have advanced our knowledge of pathophysiology of hyperuricennia and have led to the development of several new potential treatment options. Availability of new drugs will lead to better management and address the unmet need in patients with symptomatic hyperuricemia in the coming years. C1 [Shahid, Hania; Singh, Jasvinder A.] Univ Alabama Birmingham, Dept Med, Sch Med, Birmingham, AL 35294 USA. [Shahid, Hania; Singh, Jasvinder A.] Univ Alabama Birmingham, Div Epidemiol, Sch Publ Hlth, Birmingham, AL 35294 USA. [Shahid, Hania] Rawalpindi Med Coll, Rawalpindi, Pakistan. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Dept Med, Sch Med, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com FU Agency for Health Quality and Research Center for Education and Research on Therapeutics (AHRQ CERTs) [U19 HS021110]; National Institute of Arthritis, Musculoskeletal and Skin Diseases [P50 AR060772, U34 AR062891]; National Institute of Aging [U01 AG018947]; National Cancer Institute [U10 CA149950]; Patient Centered Outcomes Research Institute [CE-1304-6631] FX JA Singh is supported by grants from the Agency for Health Quality and Research Center for Education and Research on Therapeutics (AHRQ CERTs) U19 HS021110, National Institute of Arthritis, Musculoskeletal and Skin Diseases P50 AR060772 and U34 AR062891, National Institute of Aging U01 AG018947, National Cancer Institute U10 CA149950 and research contract CE-1304-6631 from the Patient Centered Outcomes Research Institute. JA Singh is also supported by the resources and the use of facilities at the VA Medical Center at Birmingham, Alabama, USA. 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 90 TC 9 Z9 11 U1 3 U2 19 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1354-3784 EI 1744-7658 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD AUG PY 2015 VL 24 IS 8 BP 1013 EP 1030 DI 10.1517/13543784.2015.1051617 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CN9FA UT WOS:000358751200003 PM 26073200 ER PT J AU D'Avanzo, C Sliwinski, C Wagner, SL Tanzi, RE Kim, DY Kovacs, DM AF D'Avanzo, Carla Sliwinski, Christopher Wagner, Steven L. Tanzi, Rudolph E. Kim, Doo Yeon Kovacs, Dora M. TI gamma-Secretase modulators reduce endogenous amyloid beta(42) levels in human neural progenitor cells without altering neuronal differentiation SO FASEB JOURNAL LA English DT Article DE presenilin; Alzheimer's disease; SGSM; Notch; ReNcell VM ID ALZHEIMERS-DISEASE; STEM-CELLS; INHIBITOR; ADULT; MODEL; TRIAL; SEMAGACESTAT; MAINTENANCE; PRESENILINS; ACTIVATION AB Soluble gamma-secretase modulators (SGSMs) selectively decrease toxic amyloid beta (A beta) peptides (A beta(42)). However, their effect on the physiologic functions of gamma-secretase has not been tested in human model systems. gamma-Secretase regulates fate determination of neural progenitor cells. Thus, we studied the impact of SGSMs on the neuronal differentiation of ReNcell VM (ReN) human neural progenitor cells (hNPCs). Quantitative PCR analysis showed that treatment of neurosphere-like ReN cell aggregate cultures with gamma-secretase inhibitors (GSIs), but not SGSMs, induced a 2- to 4-fold increase in the expression of the neuronal markers Tuj1 and doublecortin. GSI treatment also induced neuronal marker protein expression, as shown by Western blot analysis. In the same conditions, SGSM treatment selectively reduced endogenous A beta(42) levels by similar to 80%. Mechanistically, we found that Notch target gene expressions were selectively inhibited by a GSI, not by SGSM treatment. We can assert, for the first time, that SGSMs do not affect the neuronal differentiation of hNPCs while selectively decreasing endogenous A beta(42) levels in the same conditions. Our results suggest that our hNPC differentiation system can serve as a useful model to test the impact of GSIs and SGSMs on both endogenous A beta levels and gamma-secretase physiologic functions including endogenous Notch signaling. C1 [D'Avanzo, Carla; Sliwinski, Christopher; Tanzi, Rudolph E.; Kim, Doo Yeon; Kovacs, Dora M.] Harvard Univ, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Genet & Aging Res Unit,Med Sch, Charlestown, MA USA. [Wagner, Steven L.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP Kim, DY (reprint author), 114 16th St, Charlestown, MA 02129 USA. EM dkim@helix.mgh.harvard.edu; dora_kovacs@hms.harvard.edu FU U.S. National Institutes of Health, National Institute on Aging [5P01AG015379, 1RF1AG048080-01, 2R01AG014713]; Cure Alzheimer's Fund (Cure Alzheimer's Grant Stem Cell Consortium) FX The authors thank Dr. Se Hoon Choi and Ms. Jenna Garr for revising and editing the manuscript. This study was supported by the U.S. National Institutes of Health, National Institute on Aging (Grants 5P01AG015379 and 1RF1AG048080-01 to D.Y.K. and R.E.T., and Grant 2R01AG014713 to D.Y.K.), and from Cure Alzheimer's Fund (Cure Alzheimer's Grant Stem Cell Consortium; to D.Y.K., R.E.T. and S.L.W.). C.D. performed immunochemistry studies, immunofluorescence studies, analyzed data, and wrote the manuscript; C.S. performed quantitative RT-PCR studies, analyzed data, and reviewed the manuscript; S.L.W. and R.E.T. designed the soluble gamma-secretase modulators and tested for their efficacy; and D.Y.K. and D.M.K. designed the study and wrote the manuscript. The authors declare no conflicts of interest. NR 33 TC 2 Z9 2 U1 0 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD AUG PY 2015 VL 29 IS 8 BP 3335 EP 3341 DI 10.1096/fj.15-271015 PG 7 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CN9VA UT WOS:000358796900021 PM 25903103 ER PT J AU Villanueva, C Jacobson-Dickman, E Xu, C Manouvrier, S Dwyer, AA Sykiotis, GP Beenken, A Liu, Y Tommiska, J Hu, YL Tiosano, D Gerard, M Leger, J Drouin-Garraud, V Lefebvre, H Polak, M Carel, JC Phan-Hug, F Hauschild, M Plummer, L Rey, JP Raivio, T Bouloux, P Sidis, Y Mohammadi, M de Roux, N Pitteloud, N AF Villanueva, Carine Jacobson-Dickman, Elka Xu, Cheng Manouvrier, Sylvie Dwyer, Andrew A. Sykiotis, Gerasimos P. Beenken, Andrew Liu, Yang Tommiska, Johanna Hu, Youli Tiosano, Dov Gerard, Marion Leger, Juliane Drouin-Garraud, Valerie Lefebvre, Herve Polak, Michel Carel, Jean-Claude Phan-Hug, Franziska Hauschild, Michael Plummer, Lacey Rey, Jean-Pierre Raivio, Taneli Bouloux, Pierre Sidis, Yisrael Mohammadi, Moosa de Roux, Nicolas Pitteloud, Nelly TI Congenital hypogonadotropic hypogonadism with split hand/foot malformation: a clinical entity with a high frequency of FGFR1 mutations SO GENETICS IN MEDICINE LA English DT Article DE congenital hypogonadotropic hypogonadism; fibroblast growth factor receptor 1; FGF receptor substrate 2 alpha; split hand/foot malformation ID GONADOTROPIN-RELEASING-HORMONE; DOMINANT KALLMANN-SYNDROME; GROWTH-FACTOR RECEPTORS; OF-FUNCTION MUTATIONS; FOOT MALFORMATION; LIMB DEVELOPMENT; MECHANISMS; DOMAIN; INDIVIDUALS; ASSOCIATION AB Purpose: Congenital hypogonadotropic hypogonadism (CHH) and split hand/foot malformation (SHFM) are two rare genetic conditions. Here we report a clinical entity comprising the two. Methods: We identified patients with CHH and SHFM through international collaboration. Probands and available family members underwent phenotyping and screening for FGFR1 mutations. The impact of identified mutations was assessed by sequence-and structure-based predictions and/or functional assays. Results: We identified eight probands with CHH with (n = 3; Kallmann syndrome) or without anosmia (n = 5) and SHFM, seven of whom (88%) harbor FGFR1 mutations. Of these seven, one individual is homozygous for p.V429E and six individuals are heterozygous for p.G348R, p.G485R, p.Q594*, p.E670A, p.V688L, or p.L712P. All mutations were predicted by in silico analysis to cause loss of function. Probands with FGFR1 mutations have severe gonadotropin-releasing hormone deficiency (absent puberty and/or cryptorchidism and/or micropenis). SHFM in both hands and feet was observed only in the patient with the homozygous p.V429E mutation; V429 maps to the fibroblast growth factor receptor substrate 2 alpha binding domain of FGFR1, and functional studies of the p.V429E mutation demonstrated that it decreased recruitment and phosphorylation of fibroblast growth factor receptor substrate 2 alpha to FGFR1, thereby resulting in reduced mitogen-activated protein kinase signaling. Conclusion: FGFR1 should be prioritized for genetic testing in patients with CHH and SHFM because the likelihood of a mutation increases from 10% in the general CHH population to 88% in these patients. C1 [Villanueva, Carine; Leger, Juliane; Carel, Jean-Claude; de Roux, Nicolas] INSERM, Unite Mixte Rech 1141, Paris, France. [Villanueva, Carine; Leger, Juliane; Carel, Jean-Claude; de Roux, Nicolas] Univ Paris Diderot, Sorbonne Paris Cite, Hop Robert Debre, Paris, France. [Jacobson-Dickman, Elka; Dwyer, Andrew A.; Sykiotis, Gerasimos P.; Plummer, Lacey; Sidis, Yisrael; Pitteloud, Nelly] Massachusetts Gen Hosp, Harvard Reprod Endocrine Sci Ctr, Boston, MA 02114 USA. [Jacobson-Dickman, Elka; Dwyer, Andrew A.; Sykiotis, Gerasimos P.; Plummer, Lacey; Sidis, Yisrael; Pitteloud, Nelly] Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. [Jacobson-Dickman, Elka] Suny Downstate Med Ctr, Div Pediat Endocrinol, Dept Pediat, Brooklyn, NY 11203 USA. [Xu, Cheng] Shanghai Huashan Hosp, Dept Endocrinol & Diabet, Shanghai, Peoples R China. [Xu, Cheng; Dwyer, Andrew A.; Sykiotis, Gerasimos P.; Rey, Jean-Pierre; Sidis, Yisrael; Pitteloud, Nelly] Lausanne Univ Hosp CHUV, Dept Endocrinol Diabetol & Metab, Lausanne, Switzerland. [Xu, Cheng; Dwyer, Andrew A.; Sykiotis, Gerasimos P.; Rey, Jean-Pierre; Sidis, Yisrael; Pitteloud, Nelly] Univ Lausanne, Fac Biol & Med, Lausanne, Switzerland. [Manouvrier, Sylvie] Hop Jeanne de Flandre, Serv Genet Clin, Lille, France. [Beenken, Andrew; Liu, Yang; Mohammadi, Moosa] NYU, Sch Med, Dept Biochem & Mol Pharmacol, New York, NY USA. [Tommiska, Johanna; Raivio, Taneli] Univ Helsinki, Inst Biomed Physiol, Helsinki, Finland. [Tommiska, Johanna; Raivio, Taneli] Univ Helsinki, Cent Hosp, Childrens Hosp, Helsinki, Finland. [Hu, Youli; Bouloux, Pierre] UCL, Sch Med, Ctr Neuroendocrinol, London W1N 8AA, England. [Tiosano, Dov] Rambam Hlth Care Campus, Meyer Childrens Hosp, Div Pediat Endocrinol, Haifa, Israel. [Tiosano, Dov] Technion Israel Inst Technol, Bruce Rappaport Fac Med, Inst Technol, IL-31096 Haifa, Israel. [Gerard, Marion] Hop Univ Cote Nacre, Clin Genet, Caen, France. [Leger, Juliane; Carel, Jean-Claude] Hop Robert Debre, AP HP, Serv Endocrinol Diabetol Pediat, F-75019 Paris, France. [Leger, Juliane; Carel, Jean-Claude] Hop Robert Debre, AP HP, Ctr Reference Malad Endocriniennes Rares Croissan, F-75019 Paris, France. [Drouin-Garraud, Valerie] Rouen Univ Hosp, Dept Genet, Rouen, France. [Lefebvre, Herve] Univ Rouen, Inst Biomed Res, Univ Hosp Rouen, Dept Endocrinol, Rouen, France. [Polak, Michel] Univ Paris 05, Hop Univ Necker Enfants Malades, Serv Endocrinol Gynecol Diabetol Pediat, Paris, France. [Phan-Hug, Franziska; Hauschild, Michael] Lausanne Univ Hosp CHUV, Dept Pediat, Endocrinol Diabetol Unit, Lausanne, Switzerland. [de Roux, Nicolas] Hop Robert Debre, AP HP, Biochim Lab, F-75019 Paris, France. RP de Roux, N (reprint author), INSERM, Unite Mixte Rech 1141, Paris, France. EM Nicolas.deroux@inserm.fr; Nelly.Pitteloud@chuv.ch RI PITTELOUD, Nelly/K-2709-2014; Dwyer, Andrew/D-8099-2012; OI Dwyer, Andrew/0000-0002-7023-6794; Mohammadi, Moosa/0000-0003-2434-9437; Sykiotis, Gerasimos/0000-0002-9565-4941; Hauschild, Michael/0000-0002-1940-8730 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health [R01HD056264, R01DE013686]; Swiss National Science Foundation [31003A, 135648, CRSII3141960]; Academy of Finland; INSERM; DHU PROTECT; COST Action [BM1105] FX The authors are grateful to all the patients and families for their kind participation and to Kemal Topaloglu for clinical and genetic information. This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (R01HD056264 to N.P., R01DE013686 to M.M.), Swiss National Science Foundation grants (31003A, 135648 to N.P. and CRSII3141960 to N.P. and M.M.), Academy of Finland grants (to T.R. and J.T.), INSERM, the DHU PROTECT, and COST Action BM1105. NR 40 TC 7 Z9 7 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD AUG PY 2015 VL 17 IS 8 BP 651 EP 659 DI 10.1038/gim.2014.166 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA CO1ZY UT WOS:000358956200008 PM 25394172 ER PT J AU Xu, H Xiao, TF Chen, CH Li, W Meyer, CA Wu, Q Wu, D Cong, L Zhang, F Liu, JS Brown, M Liu, XS AF Xu, Han Xiao, Tengfei Chen, Chen-Hao Li, Wei Meyer, Clifford A. Wu, Qiu Wu, Di Cong, Le Zhang, Feng Liu, Jun S. Brown, Myles Liu, X. Shirley TI Sequence determinants of improved CRISPR sgRNA design SO GENOME RESEARCH LA English DT Article ID HUMAN-CELLS; ENDONUCLEASE CAS9; CANCER-CELLS; SYSTEM; SPECIFICITY; ACTIVATION; NUCLEASES; SELECTION AB The CRISPR/Cas9 system has revolutionized mammalian somatic cell genetics. Genome-wide functional screens using CRISPR/Cas9-mediated knockout or dCas9 fusion-mediated inhibition/activation (CRISPRi/a) are powerful techniques for discovering phenotype-associated gene function. We systematically assessed the DNA sequence features that contribute to single guide RNA (sgRNA) efficiency in CRISPR-based screens. Leveraging the information from multiple designs, we derived a new sequence model for predicting sgRNA efficiency in CRISPR/Cas9 knockout experiments. Our model confirmed known features and suggested new features including a preference for cytosine at the cleavage site. The model was experimentally validated for sgRNA-mediated mutation rate and protein knockout efficiency. Tested on independent data sets, the model achieved significant results in both positive and negative selection conditions and outperformed existing models. We also found that the sequence preference for CRISPRi/a is substantially different from that for CRISPR/Cas9 knockout and propose a new model for predicting sgRNA efficiency in CRISPRi/a experiments. These results facilitate the genome-wide design of improved sgRNA for both knockout and CRISPRi/a studies. C1 [Xu, Han; Xiao, Tengfei; Li, Wei; Meyer, Clifford A.; Wu, Qiu; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Xu, Han; Xiao, Tengfei; Li, Wei; Meyer, Clifford A.; Wu, Qiu; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Xu, Han; Xiao, Tengfei; Li, Wei; Meyer, Clifford A.; Wu, Qiu; Brown, Myles; Liu, X. Shirley] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. [Xiao, Tengfei; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Xiao, Tengfei; Brown, Myles] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chen, Chen-Hao] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA 02215 USA. [Wu, Qiu] Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China. [Wu, Di; Liu, Jun S.] Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. [Cong, Le; Zhang, Feng] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Cong, Le; Zhang, Feng] MIT, Dept Biol Engn, Dept Brain & Cognit Sci, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Brown, Myles] Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. [Brown, Myles] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Brown, M (reprint author), Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. EM myles_brown@dfci.harvard.edu; xsliu@jimmy.harvard.edu RI Cong, Le/M-9981-2013; OI Cong, Le/0000-0003-4725-8714; Brown, Myles/0000-0002-8213-1658 FU National Institute for Health Research (NIHR) [U01 CA180980, R01 GM113242-01]; National Science Foundation (NSF) [DMS-1120368]; Claudia Adams Barr Award in Innovative Basic Cancer Research from the Dana-Farber Cancer Institute FX We thank Drs. Carl Novina, Tim Wang, David Sabatini, Eric Lander, Ophir Shalem, and Neville Sanjana for providing the data sets and helpful discussions. The project was supported by the National Institute for Health Research (NIHR) grants U01 CA180980 (to X.S.L.), R01 GM113242-01 (to J.S.L.), National Science Foundation (NSF) grant DMS-1120368 (to J.S.L.), and the Claudia Adams Barr Award in Innovative Basic Cancer Research from the Dana-Farber Cancer Institute. NR 29 TC 43 Z9 46 U1 9 U2 61 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD AUG PY 2015 VL 25 IS 8 BP 1147 EP 1157 DI 10.1101/gr.191452.115 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA CO2AL UT WOS:000358957500007 PM 26063738 ER PT J AU Roider, EM Gauglitz, G Flaig, MJ Ruzicka, T Schauber, J AF Roider, E. M. Gauglitz, G. Flaig, M. J. Ruzicka, T. Schauber, J. TI Massive granuloma formation after long-term use of dermal fillers SO HAUTARZT LA German DT Article DE Hyaluronic acid; Wrinkle correction; Swelling; Foreign bodies; Immune reaction ID TREATMENT OPTIONS AB Since dermal fillers were introduced in 1981, millions of patients have undergone wrinkle treatment with dermal fillers. Except for autologous fat, all fillers can act as potential foreign bodies, which have the potential ability to induce an immune reaction. Persisting material may induce activation of the immune system and finally granuloma formation. Frequency, histology, and clinical presentation of such foreign body reactions may vary depending on the filler used. This case describes a patient who received innumerable filler injections over the last two decades presenting with massive facial granulomas. C1 [Roider, E. M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Charlestown, MA 02129 USA. [Roider, E. M.; Gauglitz, G.; Flaig, M. J.; Ruzicka, T.; Schauber, J.] Univ Munich, Klin & Poliklin Dermatol & Allergol, Munich, Germany. RP Roider, EM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Bldg 149,13th St, Charlestown, MA 02129 USA. EM EROIDER@cbrc2.mgh.harvard.edu NR 8 TC 0 Z9 0 U1 3 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0017-8470 EI 1432-1173 J9 HAUTARZT JI Hautarzt PD AUG PY 2015 VL 66 IS 8 BP 620 EP 623 DI 10.1007/s00105-014-3578-5 PG 4 WC Dermatology SC Dermatology GA CO8UF UT WOS:000359446900015 PM 25633722 ER PT J AU Saeki, M Sato, N Kawasaki, M Tanaka, R Nagaya, M Watanabe, T Ono, K Noda, T Zile, MR Minatoguchi, S AF Saeki, Maki Sato, Noriaki Kawasaki, Masanori Tanaka, Ryuhei Nagaya, Maki Watanabe, Takatomo Ono, Koji Noda, Toshiyuki Zile, Michael R. Minatoguchi, Shinya TI Left ventricular layer function in hypertension assessed by myocardial strain rate using novel one-beat real-time three-dimensional speckle tracking echocardiography with high volume rates SO HYPERTENSION RESEARCH LA English DT Article DE left ventricular function; left ventricular layer function; real-time three-dimensional echocardiography; speckle-tracking echocardiography ID DIASTOLIC HEART-FAILURE; LEFT ATRIAL STRUCTURE; SYSTOLIC FUNCTION; TISSUE DOPPLER; LONGITUDINAL STRAIN; FILLING PRESSURES; EJECTION FRACTION; RADIAL STRAIN; HYPERTROPHY; DEFORMATION AB We recently developed novel software to measure phasic strain rate (SR) using automated one-beat real-time three-dimensional speckle tracking echocardiography (3D-STE) with high volume rates. We tested the hypothesis that left ventricular (LV) systolic function and relaxation analyzed by SR with the novel 3D-STE in hypertension (HTN) with hypertrophy may be impaired in the endocardium before there is LV systolic dysfunction. We measured LV longitudinal, radial and circumferential SR in patients with HTN (n=80, 69 +/- 7 years) and age-matched normotensive controls (n=60, 69 +/- 10 years) using 3D-STE. HTN patients were divided into four groups according to LV geometry: normal, concentric remodeling, concentric hypertrophy and eccentric hypertrophy. We measured SR during systole as an index of systolic function, SR during isovolumic relaxation (IVR) as an index of relaxation and E/e' as an index of filling pressure. Endocardial SR during systole in HTN with concentric and eccentric hypertrophy decreased compared with that in controls despite no reduction in ejection fraction or epicardial SR. Endocardial radial SR during IVR decreased even in normal geometry, and it was further reduced in concentric remodeling and hypertrophy despite no reduction in epicardial SR. LV phasic SR assessed by 3D-STE with high volume rates is a useful index to detect early decreases in LV systolic function and to predict subclinical LV layer dysfunction in patients with HTN. C1 [Saeki, Maki; Sato, Noriaki; Tanaka, Ryuhei; Nagaya, Maki; Ono, Koji; Noda, Toshiyuki] Gifu Prefectural Gen Med Ctr, Dept Cardiol, Gifu, Japan. [Kawasaki, Masanori; Watanabe, Takatomo; Minatoguchi, Shinya] Gifu Univ, Dept Cardiol, Grad Sch Med, Gifu 5011194, Japan. [Zile, Michael R.] Med Univ S Carolina, Med Cardiol, Charleston, SC 29425 USA. [Zile, Michael R.] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. RP Kawasaki, M (reprint author), Gifu Univ, Dept Cardiol, Grad Sch Med, 1-1 Yanagido, Gifu 5011194, Japan. EM masanori@ya2.so-net.ne.jp NR 38 TC 2 Z9 2 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0916-9636 EI 1348-4214 J9 HYPERTENS RES JI Hypertens. Res. PD AUG PY 2015 VL 38 IS 8 BP 551 EP 559 DI 10.1038/hr.2015.47 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CO2VV UT WOS:000359015800006 PM 25832918 ER PT J AU Balter, ML Chen, AI Maguire, TJ Yarmush, ML AF Balter, Max L. Chen, Alvin I. Maguire, Timothy J. Yarmush, Martin L. TI The System Design and Evaluation of a 7-DOF Image-Guided Venipuncture Robot SO IEEE TRANSACTIONS ON ROBOTICS LA English DT Article DE Computer vision; kinematics; mechanism design; medical robots and systems; visual servoing ID INTERVENTIONS; TRIAL AB Accessing the venous bloodstream to deliver fluids or obtain a blood sample is the most common clinical routine practiced in the U.S. Practitioners continue to rely on manual venipuncture techniques, but success rates are heavily dependent on clinician skill and patient physiology. In the U.S., failure rates can be as high as 50% in difficult patients, making venipuncture the leading cause of medical injury. To improve the rate of first-stick success, we have developed a portable autonomous venipuncture device that robotically servos a needle into a suitable vein under image guidance. The device operates in real time, combining near-infrared and ultrasound imaging, image analysis, and a 7-degree-of-freedom (DOF) robotic system to perform the venipuncture. The robot consists of a 3-DOF gantry to image the patient's peripheral forearm veins and a miniaturized 4-DOF serial arm to guide the cannula into the selected vein under closed-loop control. In this paper, we present the system architecture of the robot and evaluate the accuracy and precision through tracking, free-space positioning, and in vitro phantom cannulation experiments. The results demonstrate sub-millimeter accuracy throughout the operating workspace of the manipulator and a high rate of success when cannulating phantom veins in a skin-mimicking tissue model. C1 [Balter, Max L.; Chen, Alvin I.; Maguire, Timothy J.; Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. [Balter, Max L.; Chen, Alvin I.; Maguire, Timothy J.] VascuLogic LLC, Piscataway, NJ 08854 USA. [Yarmush, Martin L.] Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02108 USA. RP Balter, ML (reprint author), Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. EM balterm53@gmail.com; alv6688@gmail.com; tim.maguire25@gmail.com; yarmush@rci.rutgers.edu OI Balter, Max/0000-0001-5577-356X FU NI Medical Device Industrial Innovation Grant; NSF [DGE-0937373]; NIH/NIGMS Rutgers Biotechnology Training Program [T32 GM008339]; NIH F31 Predoctoral Fellowship [EB018191] FX This work was supported by an NI Medical Device Industrial Innovation Grant. The work of M. Balter was supported by an NSF Graduate Research Fellowship (DGE-0937373). The work of A. Chen was supported by the NIH/NIGMS Rutgers Biotechnology Training Program (T32 GM008339), and an NIH F31 Predoctoral Fellowship (EB018191). NR 30 TC 4 Z9 4 U1 3 U2 24 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1552-3098 EI 1941-0468 J9 IEEE T ROBOT JI IEEE Trans. Robot. PD AUG PY 2015 VL 31 IS 4 BP 1044 EP 1053 DI 10.1109/TRO.2015.2452776 PG 10 WC Robotics SC Robotics GA CO5TK UT WOS:000359221200018 PM 26257588 ER PT J AU Moon, JJ Jenkins, MK AF Moon, James J. Jenkins, Marc K. TI T-cell repertoire The human T-cell repertoire grows up SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Editorial Material ID NAIVE; MICE C1 [Moon, James J.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Moon, James J.] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA. [Moon, James J.] Harvard Univ, Sch Med, Boston, MA USA. [Jenkins, Marc K.] Univ Minnesota, Sch Med, Ctr Immunol, Minneapolis, MN 55455 USA. [Jenkins, Marc K.] Univ Minnesota, Sch Med, Ctr Immunol, Dept Microbiol & Immunol, Minneapolis, MN 55455 USA. RP Moon, JJ (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. EM jenki002@umn.edu FU NIAID NIH HHS [U19 AI095261, R01 AI107020] NR 11 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0818-9641 EI 1440-1711 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD AUG PY 2015 VL 93 IS 7 BP 601 EP 602 DI 10.1038/icb.2015.50 PG 2 WC Cell Biology; Immunology SC Cell Biology; Immunology GA CO8MX UT WOS:000359424600001 PM 25939281 ER PT J AU Zhang, Z Adappa, ND Doghramji, LJ Chiu, AG Cohen, NA Palmer, JN AF Zhang, Zi Adappa, Nithin D. Doghramji, Laurel J. Chiu, Alexander G. Cohen, Noam A. Palmer, James N. TI Different clinical factors associated with Staphylococcus aureus and Pseudomonas aeruginosa in chronic rhinosinusitis SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE chronic rhinosinusitis; Staphylococcus aureus; Pseudomonas aeruginosa; nasal polyps; functional endoscopic sinus surgery ID REFRACTORY CHRONIC RHINOSINUSITIS; ENDOSCOPIC SINUS SURGERY; ANTIMICROBIAL RESISTANCE; NASAL POLYPS; BACTERIOLOGICAL FINDINGS; MAXILLARY SINUSITIS; ASTHMA; MICROBIOLOGY; INFLAMMATION; FEATURES AB BackgroundStaphylococcus aureus and Pseudomonas aeruginosa are common culture isolates in chronic rhinosinusitis (CRS). We aimed to determine whether they were associated with different clinical factors of CRS. MethodsAdult CRS patients who underwent functional endoscopic sinus surgery (FESS) between October 1, 2007 and December 31, 2011 were recruited. Patient demographics, Lund-Mackay computed tomography (CT) scores, 22-item Sino-Nasal Outcome Test (SNOT-22) scores, disease characteristics, and medication use were collected prior to FESS. Intraoperative culture was obtained in a standard manner. We compared patients with isolates of S. aureus or P. aeruginosa to patients with other culture results and no bacterial growth, respectively. Multivariate logistic regression was performed. ResultsA total of 376 patients met criteria; 104 patients (28%) had S. aureus, 32 (9%) had P. aeruginosa, and 10 patients (3%) had no bacterial growth. After adjusting for all clinical factors, compared to patients with positive culture other than S. aureus, patients with S. aureus had 1.9 times increased odds of having nasal polyps (odds ratio [OR] = 1.9; 95% confidence interval [CI], 1.0 to 3.3; p = 0.036); when compared to patients with positive culture other than P. aeruginosa, patients with P. aeruginosa had 7.8 times increased odds of having prior FESS (OR = 7.8; 95% CI, 2.1 to 28.9; p = 0.002) (91% vs 58%; p < 0.001) and 3.6 times increased odds of having diabetes with marginal significance (OR = 3.6; 95% CI, 1.0 to 13.2; p = 0.053). The sample size in the no bacterial growth group was too small to draw firm conclusions. ConclusionS. aureus was more common in CRS patients with nasal polyps, whereas P. aeruginosa was more common in CRS patients with prior FESS history and possibly diabetes. C1 [Zhang, Zi] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Adappa, Nithin D.; Doghramji, Laurel J.; Cohen, Noam A.; Palmer, James N.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Perelman Sch Med, Philadelphia, PA 19104 USA. [Chiu, Alexander G.] Univ Arizona, Dept Surg, Tucson, AZ USA. [Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Zhang, Z (reprint author), 8th Floor,Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM zizhang@mail.med.upenn.edu OI Cohen, Noam/0000-0002-9462-3932 NR 40 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2042-6976 EI 2042-6984 J9 INT FORUM ALLERGY RH JI Int. Forum Allergy Rhinol. PD AUG PY 2015 VL 5 IS 8 BP 724 EP 733 DI 10.1002/alr.21532 PG 10 WC Otorhinolaryngology SC Otorhinolaryngology GA CO3JQ UT WOS:000359053700009 PM 25899601 ER PT J AU Yao, WC Bleier, BS AF Yao, William C. Bleier, Benjamin S. TI Centrifugal frontal sinus dissection technique: addressing anterior and posterior frontoethmoidal air cells SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE Endoscopic Sinus Surgery; Extended frontal sinusotomy; Frontal sinusotomy; Sinus Surgery; Chronic Rhinosinusitis ID SURGERY; RECESS; EXPERIENCE; OSTIUM C1 [Yao, William C.; Bleier, Benjamin S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol Head & Neck Surg, Boston, MA USA. RP Bleier, BS (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM benjamin_bleier@meei.harvard.edu NR 16 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2042-6976 EI 2042-6984 J9 INT FORUM ALLERGY RH JI Int. Forum Allergy Rhinol. PD AUG PY 2015 VL 5 IS 8 BP 761 EP 763 DI 10.1002/alr.21523 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA CO3JQ UT WOS:000359053700014 PM 25914121 ER PT J AU Leffert, LR AF Leffert, L. R. TI What's new in obstetric anesthesia? Focus on preeclampsia SO INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA LA English DT Article; Proceedings Paper CT Sol Shnider Obstet Anesthesia Meeting of the Society-for-Obstetric-Anesthesia-and-Perinatology CY MAR, 2015 CL San Francisco, CA SP Soc Obstet Anesthesia & Perinatol ID RANDOMIZED-CONTROLLED-TRIAL; HYPERTENSIVE DISORDERS; BLOOD-PRESSURE; UNITED-STATES; PREGNANCY; WOMEN; RISK; PREVENTION; ECLAMPSIA; STROKE AB Recent advances in the diagnosis, pathogenesis, and understanding of preeclampsia-related morbidity provide opportunities to optimize clinical management of the mother and fetus. These discoveries are timely, as contemporary data suggest that the prevalence of preeclampsia, affecting 7.5% of pregnancies globally and 2-5% in the USA, has increased by up to 30% over the last decade. Managing pregnant patients with preeclampsia can be challenging for all members of the obstetric care team due to the disease's multi-organ system maternal and fetal effects. This review presents recent updates in the definition of preeclampsia, etiology, comorbidities and therapeutic interventions and discusses how they impact the care of these high-risk patients. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Leffert, L. R.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Leffert, LR (reprint author), Massachusetts Gen Hosp, Chair Obstetr Anesthesia Div, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM lleffert@partners.org NR 61 TC 4 Z9 4 U1 1 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-289X EI 1532-3374 J9 INT J OBSTET ANESTH JI Int. J. Obstet. Anesth. PD AUG PY 2015 VL 24 IS 3 BP 264 EP 271 DI 10.1016/j.ijoa.2015.03.008 PG 8 WC Anesthesiology; Obstetrics & Gynecology SC Anesthesiology; Obstetrics & Gynecology GA CN9YO UT WOS:000358807300010 PM 25936785 ER PT J AU Doulamis, IP Economopoulos, KP AF Doulamis, Ilias P. Economopoulos, Konstantinos P. TI Transumbilical Roux-en-Y gastric bypass in morbidly obese patients: A systematic review SO INTERNATIONAL JOURNAL OF SURGERY LA English DT Review DE Transumbilical; Single-incision; Roux-en-Y gastric bypass ID LAPAROSCOPIC BARIATRIC SURGERY; SINGLE-INCISION; GASTROJEJUNAL ANASTOMOSIS; ACCESS; SILS AB Background: Transumbilical single-incision Roux-en-Y gastric bypass constitutes a delicate technique of the conventional laparoscopic approach, which is the gold standard for the treatment of obesity. Methods: In order to investigate its efficacy and feasibility, PubMed was searched up to April 25th, 2015. Ten studies reporting on 247 patients with a mean age of 37.3 years were eligible. Results: Mean preoperative Body Mass Index was 42.4 kg/m(2). Most common comorbidities were diabetes and dyslipidemia. Mean operative time was 128.5 min and mean length of hospital stay was 3.3 days. No conversions to open surgery were reported. Conclusion: Clinical outcomes of the transumbilical Roux-en-Y gastric bypass appear to be comparable with those of the conventional laparoscopic one. However, more trials are necessary to elucidate all of its aspects. (C) 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved. C1 [Doulamis, Ilias P.; Economopoulos, Konstantinos P.] Soc Jr Doctors, Athens, Greece. [Economopoulos, Konstantinos P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Economopoulos, KP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 101 Merrimac St, Boston, MA 02114 USA. EM ledoul@hotmail.com; keconomopoulos@mgh.harvard.edu OI Economopoulos, Konstantinos/0000-0003-4856-0405 NR 25 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1743-9191 EI 1743-9159 J9 INT J SURG JI Int. J. Surg. PD AUG PY 2015 VL 20 BP 153 EP 157 DI 10.1016/j.ijsu.2015.06.077 PG 5 WC Surgery SC Surgery GA CO6YX UT WOS:000359305200027 PM 26166741 ER PT J AU Wheatley, LM Plaut, M Schwaninger, JM Banerji, A Castells, M Finkelman, FD Gleich, GJ Guttman-Yassky, E Mallal, SAK Naisbitt, DJ Ostrov, DA Phillips, EJ Pichler, WJ Platts-Mills, TAE Roujeau, JC Schwartz, LB Trepanier, LA AF Wheatley, Lisa M. Plaut, Marshall Schwaninger, Julie M. Banerji, Aleena Castells, Mariana Finkelman, Fred D. Gleich, Gerald J. Guttman-Yassky, Emma Mallal, Simon A. K. Naisbitt, Dean J. Ostrov, David A. Phillips, Elizabeth J. Pichler, Werner J. Platts-Mills, Thomas A. E. Roujeau, Jean-Claude Schwartz, Lawrence B. Trepanier, Lauren A. TI Report from the National Institute of Allergy and Infectious Diseases workshop on drug allergy SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Drug allergy; drug hypersensitivity; desensitization; pharmacogenomics; Stevens-Johnson syndrome; toxic epidermal necrolysis; hapten hypothesis; altered peptide repertoire hypothesis; pharmacologic interaction with immune receptor hypothesis ID TOXIC EPIDERMAL NECROLYSIS; STEVENS-JOHNSON-SYNDROME; BETA-LACTAM ANTIBIOTICS; INDUCED LIVER-INJURY; RED MEAT ALLERGY; HYPERSENSITIVITY REACTIONS; CYSTIC-FIBROSIS; PENICILLIN ALLERGY; PEPTIDE REPERTOIRE; CROSS-REACTIVITY AB Allergic reactions to drugs are a serious public health concern. In 2013, the Division of Allergy, Immunology, and Transplantation of the National Institute of Allergy and Infectious Diseases sponsored a workshop on drug allergy. International experts in the field of drug allergy with backgrounds in allergy, immunology, infectious diseases, dermatology, clinical pharmacology, and pharmacogenomics discussed the current state of drug allergy research. These experts were joined by representatives from several National Institutes of Health institutes and the US Food and Drug Administration. The participants identified important advances that make new research directions feasible and made suggestions for research priorities and for development of infrastructure to advance our knowledge of the mechanisms, diagnosis, management, and prevention of drug allergy. The workshop summary and recommendations are presented herein. C1 [Wheatley, Lisa M.; Plaut, Marshall; Schwaninger, Julie M.] NIAID, Div Allergy Immunol & Transplantat, NIH, Rockville, MD 20852 USA. [Banerji, Aleena] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Castells, Mariana] Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, Drug Hypersensit & Desensitizat Ctr, Boston, MA 02115 USA. [Finkelman, Fred D.] Univ Cincinnati, Div Allergy Immunol & Rheumatol, Dept Internal Med, Coll Med,Dept Med,Cincinnati Vet Affairs Med Ctr, Cincinnati, OH 45221 USA. [Finkelman, Fred D.] Cincinnati Childrens Hosp Med Ctr, Div Immunobiol, Cincinnati, OH 45229 USA. [Gleich, Gerald J.] Univ Utah, Dept Dermatol, Salt Lake City, UT USA. [Gleich, Gerald J.] Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA. [Guttman-Yassky, Emma] Mt Sinai Med Ctr, Dept Dermatol, New York, NY 10029 USA. [Guttman-Yassky, Emma] Mt Sinai Med Ctr, Inst Immunol, Icahn Sch Med, New York, NY 10029 USA. [Mallal, Simon A. K.] Vanderbilt Univ, Sch Med, Dept Med, Ctr Translat Immunol & Infect Dis, Nashville, TN 37212 USA. [Mallal, Simon A. K.; Phillips, Elizabeth J.] Murdoch Univ, Inst Immunol & Infect Dis, Murdoch, WA 6150, Australia. [Naisbitt, Dean J.] Univ Liverpool, Dept Pharmacol, MRC, Ctr Drug Safety Sci, Liverpool L69 3BX, Merseyside, England. [Ostrov, David A.] Univ Florida, Coll Med, Div Expt Pathol, Dept Pathol Immunol & Lab Med, Gainesville, FL USA. [Phillips, Elizabeth J.] Vanderbilt Univ, Med Ctr, Dept Med, Div Infect Dis, Nashville, TN USA. [Pichler, Werner J.] ADR AC GMBH, CH-3008 Bern, Switzerland. [Platts-Mills, Thomas A. E.] Univ Virginia, Dept Med, Asthma & Allerg Dis Ctr, Charlottesville, VA USA. [Roujeau, Jean-Claude] Univ Paris Est Creteil, F-94010 Creteil, France. [Schwartz, Lawrence B.] Virginia Commonwealth Univ, Dept Internal Med, Div Rheumatol Allergy & Immunol, Richmond, VA 23284 USA. [Trepanier, Lauren A.] Univ Wisconsin Madison, Sch Vet Med, Dept Med Sci, Madison, WI USA. RP Wheatley, LM (reprint author), NIAID, NIH, Div Allergy Immunol & Transplantat, Rockville, MD 20852 USA. EM lisa.wheatley@nih.gov FU Merck; Sanofi; National Institutes of Health (NIH) Desensitization; National Institute of Allergy and Infectious Diseases (NIAID); GlaxoSmithKline; Regeneron; Celgene; BMS; Janssen; NHMRC Australia; NIH; UpToDate; Roche; Lilly; Boehringer Ingelheim; AiCuris; Menarini; NIAID; AB Science; Novartis; OM-Pharma; Science Technologie; Astellas pharma; Sanofi Aventis; Dyax; ViroPharma; HELIX; CSL Behring FX M. Castells has received consultancy fees from Merck and Sanofi, is employed by BWH, has received research support from National Institutes of Health (NIH) Desensitization (pending), has received royalties from UpToDate, and has received travel support from the American Academy of Allergy, Asthma & Immunology (AAAAI) as a member of the Board of Directors. F. D. Finkelman has received travel support and research support from the National Institute of Allergy and Infectious Diseases (NIAID) and has a relevant patent pending with the University of Cincinnati. G. J. Gleich has received travel support from the University of Utah, has received consultancy fees from GlaxoSmithKline, and has provided expert testimony for plaintiffs' attorneys. E. Guttman-Yassky is a board member for Sanofi Aventis, Regeneron, Stiefel/GlaxoSmithKline, Medimmune, Celgene, Anacor, and Leo Pharma; has received consultancy fees from Regeneron, Sanofi Aventis, Medimmune, Celgene, Stiefel/GlaxoSmithKline, Celsus, BMS, Amgen, and Drais; and has received research support from Regeneron, Celgene, BMS, and Janssen. S. A. K. Mallal has equity in IIID Ltd, which has a patent for HLA-B*5701 screening for abacavir hypersensitivity. D. J. Naisbitt, D. A. Ostrov, and L. A. Trepanier have received travel support from the NIH/NIAID. E. J. Phillips has received research support from NHMRC Australia and from the NIH, has received personal fees from UpToDate, and is a codirector of the company that holds the patent for HLA-B*57:01 testing for abacavir HSR; honoraria were paid to her institution by Merck Pty Ltd and ViiV. W.J. Pichler has received consultancy fees from Roche, Lilly, Boehringer Ingelheim, AiCuris, and Menarini. T. A. E. Platts-Mills has received research support from the NIAID and has received consultancy fees and travel support from Thermo Fisher/Phadia. J.-C. Roujeau has received travel support from the NIH/NIAID; is a board member for Pfizer, Menarini, Vertex, Servier, OM Pharma, and Boehringer-Ingelheim; has received consultancy fees from AB Science; has provided expert testimony for McNeil consumers (a branch of J & J); has received research support from GlaxoSmithKline, Novartis, Boehringer Ingelheim, OM-Pharma, Science & Technologie, Astellas pharma, Menarini; has received lecture fees from Menarini; and has received payment for development of educational presentations from Janssen. L. B. Schwartz has received travel support from the NIH/NIAID; has received consultancy fees from Sanofi Aventis, Dyax, ViroPharma, and HELIX; has received research support from CSL Behring and Dyax; has received royalties from VCU Tech Transfer; and is an Associate Editor of and has received an honorarium from the Journal of Clinical Immunology. The rest of the authors declare that they have no relevant conflicts of interest. NR 78 TC 6 Z9 6 U1 0 U2 10 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 2015 VL 136 IS 2 BP 262 EP + DI 10.1016/j.jaci.2015.05.027 PG 12 WC Allergy; Immunology SC Allergy; Immunology GA CO2RS UT WOS:000359004900006 PM 26254053 ER PT J AU Hasegawa, K Tsugawa, Y Chang, YC Camargo, CA AF Hasegawa, Kohei Tsugawa, Yusuke Chang, Yuchiao Camargo, Carlos A., Jr. TI Risk of an asthma exacerbation after bariatric surgery in adults SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Acute asthma; emergency department; hospitalization; obesity; bariatric surgery; weight reduction; self-controlled case series study ID BODY-MASS INDEX; RANDOMIZED CONTROLLED-TRIALS; CLINICAL-PRACTICE; EMERGENCY-DEPARTMENT; PULMONARY-FUNCTION; OBESE-PATIENTS; WEIGHT-LOSS; AIRWAY; METAANALYSIS; SEVERITY AB Background: Research on nonsurgical weight loss interventions has failed to demonstrate consistent efficacy on asthma control, although these interventions resulted in only modest weight reductions. Objective: We sought to test the hypothesis that bariatric surgery is associated with a rapid and sustained decrease in risk of asthma exacerbation. Methods: We performed a self-controlled case series study of 2261 obese patients with asthma aged 18 to 54 years who underwent bariatric surgery using the population-based emergency department (ED) and inpatient sample in 3 states (California, Florida, and Nebraska). The primary outcome was an ED visit or hospitalization for asthma exacerbation from 2005 through 2011. We used conditional logistic regression to compare each patient's risk of the outcome event during sequential 12-month periods using presurgery months 13 to 24 as the reference period. Results: During the reference period, 22.0% (95% CI, 20.3% to 23.7%) of patients had an ED visit or hospitalization for asthma exacerbation. In the subsequent 12-month presurgery period, the risk did not materially change (21.7%; 95% CI, 20.0% to 23.4%), with an odds ratio (OR) of 0.98 (95% CI, 0.85-1.13) compared with the reference period. By contrast, significantly fewer ED visits or hospitalizations for asthma exacerbation occurred within 12 months after bariatric surgery (10.9%; 95% CI, 9.6% to 12.2%), corresponding to an OR of 0.42 (95% CI, 0.35-0.50). Similarly, in the subsequent period of 13 to 24 months after bariatric surgery, the risk remained significantly lower (10.9%; 95% CI, 9.6% to 12.2%), corresponding to an OR of 0.42 (95% CI, 0.35-0.50). Conclusion: In obese patients the risk of an ED visit or hospitalization for asthma exacerbation decreased by half after bariatric surgery. This reduction suggests the effectiveness of significant weight loss on asthma morbidity. C1 [Hasegawa, Kohei; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Chang, Yuchiao] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Tsugawa, Yusuke] Harvard Interfac Initiat Hlth Policy, Cambridge, MA USA. RP Hasegawa, K (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM khasegawa1@partners.org FU Eleanor and Miles Shore Fellowship Program (Boston, Mass) FX K.H. was supported in part by the Eleanor and Miles Shore Fellowship Program (Boston, Mass). NR 35 TC 6 Z9 6 U1 1 U2 1 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 2015 VL 136 IS 2 BP 288 EP + DI 10.1016/j.jaci.2014.12.1931 PG 15 WC Allergy; Immunology SC Allergy; Immunology GA CO2RS UT WOS:000359004900009 PM 25670012 ER PT J AU Chou, J Badran, YR Yee, CSK Bainter, W Ohsumi, TK Al-Hammadi, S Pai, SY Feske, S Geha, RS AF Chou, Janet Badran, Yousef R. Yee, Christina S. K. Bainter, Wayne Ohsumi, Toshiro K. Al-Hammadi, Suleiman Pai, Sung-Yun Feske, Stefan Geha, Raif S. TI A novel mutation in ORAI1 presenting with combined immunodeficiency and residual T-cell function SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID LYMPHOCYTE FUNCTION; PROTEINS; IMMUNITY C1 [Chou, Janet; Badran, Yousef R.; Yee, Christina S. K.; Bainter, Wayne; Geha, Raif S.] Childrens Hosp, Div Immunol, Boston, MA 02115 USA. [Chou, Janet; Badran, Yousef R.; Yee, Christina S. K.; Bainter, Wayne; Geha, Raif S.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Ohsumi, Toshiro K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Ohsumi, Toshiro K.] Harvard Univ, Sch Med, Boston, MA USA. [Al-Hammadi, Suleiman] United Arab Emirates Univ, Dept Pediat, Al Ain, U Arab Emirates. [Pai, Sung-Yun] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Pai, Sung-Yun] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Feske, Stefan] NYU, Dept Pathol, Langone Med Ctr, New York, NY 10016 USA. RP Chou, J (reprint author), Childrens Hosp, Div Immunol, 300 Longwood Ave, Boston, MA 02115 USA. EM raif.geha@childrens.harvard.edu OI Feske, Stefan/0000-0001-5431-8178 FU NIAID NIH HHS [AI-094017, R01 AI097302, R03 AI094017, T32 AI007512, P01 AI076210]; PHS HHS [UO1AIO67854] NR 12 TC 4 Z9 4 U1 1 U2 1 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 2015 VL 136 IS 2 BP 479 EP + DI 10.1016/j.jaci.2015.03.050 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA CO2RS UT WOS:000359004900031 PM 26070885 ER PT J AU Jartti, T Hasegawa, K Mansbach, JM Piedra, PA Camargo, CA AF Jartti, Tuomas Hasegawa, Kohei Mansbach, Jonathan M. Piedra, Pedro A. Camargo, Carlos A., Jr. TI Rhinovirus-induced bronchiolitis: Lack of association between virus genomic load and short-term outcomes SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID LENGTH-OF-STAY; REAL-TIME PCR; PROSPECTIVE MULTICENTER; CHILDREN; INFECTIONS; DIAGNOSIS; SEVERITY; ETIOLOGY; DISEASE; ASTHMA C1 [Jartti, Tuomas] Turku Univ Hosp, Dept Pediat, FIN-20520 Turku, Finland. [Hasegawa, Kohei; Camargo, Carlos A., Jr.] Harvard Univ, Dept Emergency Med, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Mansbach, Jonathan M.] Boston Childrens Hosp, Dept Med, Boston, MA USA. [Piedra, Pedro A.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Piedra, Pedro A.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. RP Jartti, T (reprint author), Turku Univ Hosp, Dept Pediat, FIN-20520 Turku, Finland. EM tuomas.jartti@utu.fi FU NIAID NIH HHS [U01 AI-67693] NR 20 TC 3 Z9 4 U1 1 U2 1 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 2015 VL 136 IS 2 BP 509 EP + DI 10.1016/j.jaci.2015.02.021 PG 15 WC Allergy; Immunology SC Allergy; Immunology GA CO2RS UT WOS:000359004900043 PM 25840721 ER PT J AU Sakadzic, S AF Sakadzic, Sava TI At long last, PAT hats for the lab rats SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Editorial Material C1 [Sakadzic, Sava] Massachusetts Gen Hosp, Dept Radiol, Opt Div, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. [Sakadzic, Sava] Harvard Univ, Sch Med, Charlestown, MA USA. RP Sakadzic, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, Opt Div, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. EM sava.sakadzic@mgh.harvard.edu NR 4 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD AUG PY 2015 VL 35 IS 8 BP 1223 EP 1223 DI 10.1038/jcbfm.2015.136 PG 1 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA CN9WN UT WOS:000358801300001 PM 26082018 ER PT J AU Rigby, MR Harris, KM Pinckney, A DiMeglio, LA Rendell, MS Felner, EI Dostou, JM Gitelman, SE Griffin, KJ Tsalikian, E Gottlieb, PA Greenbaum, CJ Sherry, NA Moore, WV Monzavi, R Willi, SM Raskin, P Keyes-Elstein, L Long, SA Kanaparthi, S Lim, N Phippard, D Soppe, CL Fitzgibbon, ML McNamara, J Nepom, GT Ehlers, MR AF Rigby, Mark R. Harris, Kristina M. Pinckney, Ashley DiMeglio, Linda A. Rendell, Marc S. Felner, Eric I. Dostou, Jean M. Gitelman, Stephen E. Griffin, Kurt J. Tsalikian, Eva Gottlieb, Peter A. Greenbaum, Carla J. Sherry, Nicole A. Moore, Wayne V. Monzavi, Roshanak Willi, Steven M. Raskin, Philip Keyes-Elstein, Lynette Long, S. Alice Kanaparthi, Sai Lim, Noha Phippard, Deborah Soppe, Carol L. Fitzgibbon, Margret L. McNamara, James Nepom, Gerald T. Ehlers, Mario R. CA Immune Tolerance Network ITN TIDAL TI Alefacept provides sustained clinical and immunological effects in new-onset type 1 diabetes patients SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID BETA-CELL FUNCTION; ANTI-CD3 MONOCLONAL-ANTIBODY; C-PEPTIDE RESPONSES; MEMORY T-CELLS; DOUBLE-BLIND; NOD MICE; CONTROLLED-TRIAL; PHASE-2 TRIAL; PD-1 PATHWAY; PSORIASIS AB BACKGROUND. Type 1 diabetes (T1D) results from destruction of pancreatic beta cells by autoreactive effector T cells. We hypothesized that the immunomodulatory drug alefacept would result in targeted quantitative and qualitative changes in effector T cells and prolonged preservation of endogenous insulin secretion by the remaining 13 cells in patients with newly diagnosed T1D. METHODS. In a multicenter, randomized, double-blind, placebo-controlled trial, we compared alefacept (two 12-week courses of 15 mg/wk i.m., separated by a 12-week pause) with placebo in patients with recent onset of T1D. Endpoints were assessed at 24 months and included meal-stimulated C-peptide AUC, insulin use, hypoglycemic events, and immunologic responses. RESULTS. A total of 49 patients were enrolled. At 24 months, or 15 months after the last dose of alefacept, both the 4-hour and the 2-hour C-peptide AUCs were significantly greater in the treatment group than in the control group (P = 0.002 and 0.015, respectively). Exogenous insulin requirements were lower (P = 0.002) and rates of major hypoglycemic events were about 50% reduced (P < 0.001) in the alefacept group compared with placebo at 24 months. There was no apparent between-group difference in glycemic control or adverse events. Alefacept treatment depleted CD4+ and CD8+ central memory T cells (Tcm) and effector memory T cells (Tem) (P < 0.01), preserved Tregs, increased the ratios of Treg to Tem and Tcm (P < 0.01), and increased the percentage of PD-1(+)CD(4+). Tem and Tcm (P < 0.01). CONCLUSIONS. In patients with newly diagnosed T1D, two 12-week courses of alefacept preserved C-peptide secretion, reduced insulin use and hypoglycemic events, and induced favorable immunologic profiles at 24 months, well over 1 year after cessation of therapy. C1 [Rigby, Mark R.; DiMeglio, Linda A.] Indiana Univ Sch Med, Riley Hosp Children, Dept Pediat, Sect Pediat Endocrinol & Diabetol, Indianapolis, IN 46202 USA. [Harris, Kristina M.; Kanaparthi, Sai; Lim, Noha; Phippard, Deborah] ITN, Biomarker Discovery Res, Bethesda, MD USA. [Pinckney, Ashley; Keyes-Elstein, Lynette] Rho Inc, Fed Syst Div, Biostat, Chapel Hill, NC USA. [Rendell, Marc S.] Creighton Diabet Ctr, Omaha, NE USA. [Felner, Eric I.] Emory Univ, Sch Med, Dept Pediat, Div Pediat Endocrinol, Atlanta, GA USA. [Dostou, Jean M.] Univ N Carolina, Sch Med Chapel Hill, Dept Med, Div Endocrinol, Durham, NC USA. [Gitelman, Stephen E.] UCSF, Dept Pediat, Div Endocrinol, San Francisco, CA USA. [Griffin, Kurt J.] Univ Arizona, Dept Pediat Endocrinol, Tucson, AZ USA. [Tsalikian, Eva] Univ Iowa, Dept Pediat, Div Pediat Endocrinol & Diabet, Iowa City, IA 52242 USA. [Gottlieb, Peter A.] Univ Colorado, Sch Med, Barbara Davis Ctr Childhood Diabet, Aurora, CO USA. [Greenbaum, Carla J.; Long, S. Alice; Nepom, Gerald T.] Virginia Mason, Benaroya Res Inst, Seattle, WA USA. [Sherry, Nicole A.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Moore, Wayne V.] Univ Missouri, Childrens Mercy Hosp, Pediat Endocrinol, Kansas City, MO 64108 USA. [Monzavi, Roshanak] USC Keck Sch Med, Dept Pediat, Childrens Hosp Los Angeles, Ctr Endocrinol Diabet & Metab, Los Angeles, CA USA. [Willi, Steven M.] Childrens Hosp Philadelphia, Dept Endocrinol, Philadelphia, PA 19104 USA. [Raskin, Philip] Univ Texas SW Med Ctr Dallas, Div Endocrinol, Dept Internal Med, Dallas, TX 75390 USA. [Soppe, Carol L.; Ehlers, Mario R.] ITN, Clin Trials Grp, San Francisco, CA USA. [Fitzgibbon, Margret L.; McNamara, James] NIAID, Div Allergy Immunol & Transplantat, Rockville, MD USA. RP Rigby, MR (reprint author), Pharmaceut Co Johnson & Johnson, Janssen R&D, Translat Med Immunol Dev, 1460 McKean Rd, Spring House, PA 19477 USA. EM mrigby@its.jnj.com OI Nepom, Gerald/0000-0002-8063-1464 FU National Institute of Allergy and Infectious Diseases (NIAID) [NO1-AI-15416, UM1AI109565]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Indiana Clinical and Translational Sciences Institute - NIH, National Center for Advancing Translational Sciences (NCATS) [TR000006]; National Center for Research Resources (NCRR) [UL1 RR024131, UL1 TR000004]; NCATS, NIH [UL1 RR024131, UL1 TR000004]; NCRR [UL1RR024134, UL1TR000003]; NCATS [UL1RR024134, UL1TR000003]; Bayer HealthCare LLC, Diabetes Care FX Funding/Support: The trial was conducted by the ITN and sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) under Award Numbers NO1-AI-15416 and UM1AI109565. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Additional funding was provided by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). This project was in part supported, at Indiana University, by the Indiana Clinical and Translational Sciences Institute, funded in part by Grant Number TR000006 from the NIH, National Center for Advancing Translational Sciences (NCATS), Clinical and Translational Sciences Award; at UCSF, by Grant Numbers UL1 RR024131 and UL1 TR000004 from the National Center for Research Resources (NCRR) and the NCATS, NIH; at CHOP, by Grants UL1RR024134 and UL1TR000003 from the NCRR and the NCATS. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. Astellas provided alefacept (Amevive) and gave input regarding dosage and safety, but had no direct involvement with study design, conduct, or management; data collection, analysis, or interpretation; or manuscript preparation. There are no agreements concerning confidentiality of the data between Astellas, the sponsor, and the authors or the institutions named in the credit lines. The authors provided Astellas a copy of the original manuscript prior to submission. Bayer HealthCare LLC, Diabetes Care provided blood glucose monitoring supplies through an investigator-sponsored research grant. The authors provided Bayer a copy of the original manuscript prior to submission. NR 46 TC 29 Z9 29 U1 1 U2 7 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 PY 2015 VL 125 IS 8 BP 3285 EP 3296 DI 10.1172/JCI81722 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CO3CS UT WOS:000359034800035 PM 26193635 ER PT J AU Lau, A Dodson, TB Sonis, ST Kaban, LB AF Lau, Agnes Dodson, Thomas B. Sonis, Stephen T. Kaban, Leonard B. TI An Outcomes Study of 40 Years of Graduates of a General Practice Dental Residency SO JOURNAL OF DENTAL EDUCATION LA English DT Article DE dental residency; dental internship; graduate dental education; advanced dental education; general practice residency; postdoctoral general dentistry AB Assessing program quality and outcomes is essential to improve postgraduate dental education. This study's aims were to document career direction and practice patterns of graduates of the Brigham and Women's Hospital (BWH) General Practice Residency (GPR), to compare BWH GPR outcomes to those of other American GPRs, and to identify characteristics of the BWH GPR program that trainees valued. This was a retrospective cohort study with a sample comprised of BWH GPR graduates between 1973 and 2013. Outcomes examined included pursuit of specialty training and positions on academic or hospital staff. Data sources were a survey of BWH GPR graduates and published national surveys. Of the 190 BWH graduates (95% of total) who were located and contacted, 133 (70% response rate) completed the survey. Compared to national survey data, BWH GPR graduates were significantly more likely to be specialists, full-time hospital staff, or full-time or part-time dental school faculty. Most BWH graduates (96.2%) ranked the program as outstanding or good. Faculty characteristics were considered by BWH graduates to be the most important factors in judging program quality. Since faculty characteristics were the most important factors in residents' judgment of program quality, GPR programs should recruit, maintain, and develop a quality faculty in order to attract students. Dr. Lau is Assistant Professor, Department of Oral and Maxillofacial Surgery, Harvard School of Dental Medicine, Chief of the Division of Dentistry at Massachusetts General Hospital, and former Director of Brigham and Women's Hospital/Massachusetts General Hospital Harvard General Practice Residency in Dentistry; Dr. Dodson is Professor and Chair, Department of Oral and Maxillofacial Surgery and Associate Dean for Hospital Affairs, University of Washington School of Dentistry; Dr. Sonis is Professor, Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, and Chief of the Division of Oral Medicine and Dentistry, Brigham and Women's Hospital; and Dr. Kaban is Walter C. Guralnick Professor and Chair, Department of Oral and Maxillofacial Surgery, Harvard School of Dental Medicine and Massachusetts General Hospital. Direct correspondence to Dr. Agnes Lau, Division of Dentistry, Massachusetts General Hospital, 165 Cambridge Street, Suite 401, Boston, MA 02114; 617-726-1076; alau@partners.org. C1 [Lau, Agnes] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Cambridge, MA 02138 USA. [Lau, Agnes] Massachusetts Gen Hosp, Div Dent, Boston, MA 02114 USA. [Lau, Agnes] Massachusetts Gen Hosp, Brigham & Womens Hosp, Harvard Gen Practice Residency Dent, Boston, MA 02114 USA. [Dodson, Thomas B.] Univ Washington, Dept Oral & Maxillofacial Surg, Sch Dent, Seattle, WA 98195 USA. [Dodson, Thomas B.] Univ Washington, Hosp Affairs, Sch Dent, Seattle, WA 98195 USA. [Sonis, Stephen T.; Kaban, Leonard B.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Cambridge, MA 02138 USA. [Sonis, Stephen T.] Brigham & Womens Hosp, Div Oral Med & Dent, Boston, MA 02115 USA. [Kaban, Leonard B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lau, A (reprint author), Massachusetts Gen Hosp, Div Dent, 165 Cambridge St,Suite 401, Boston, MA 02114 USA. EM alau@partners.org NR 6 TC 0 Z9 0 U1 1 U2 2 PU AMER DENTAL EDUCATION ASSOC-ADEA PI WASHINGTON PA 655 K STREET NW, SUITE 800, WASHINGTON, DC 20001 USA SN 0022-0337 EI 1930-7837 J9 J DENT EDUC JI J. Dent. Educ. PD AUG PY 2015 VL 79 IS 8 BP 888 EP 896 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CO3CN UT WOS:000359034300002 PM 26246526 ER PT J AU Susarla, SM Dodson, TB Lopez, J Swanson, EW Calotta, N Peacock, ZS AF Susarla, Srinivas M. Dodson, Thomas B. Lopez, Joseph Swanson, Edward W. Calotta, Nicholas Peacock, Zachary S. TI Do Quantitative Measures of Research Productivity Correlate with Academic Rank in Oral and Maxillofacial Surgery? SO JOURNAL OF DENTAL EDUCATION LA English DT Article DE dental education; oral and maxillofacial surgery; dental faculty; academic dental careers; academic promotion; research activity ID H-INDEX; GENDER DISPARITIES; UNITED-STATES; OTOLARYNGOLOGY; PERFORMANCE; DEPARTMENTS AB Academic promotion is linked to research productivity. The purpose of this study was to assess the correlation between quantitative measures of academic productivity and academic rank among academic oral and maxillofacial surgeons. This was a cross-sectional study of full-time academic oral and maxillofacial surgeons in the United States. The predictor variables were categorized as demographic (gender, medical degree, research doctorate, other advanced degree) and quantitative measures of academic productivity (total number of publications, total number of citations, maximum number of citations for a single article, I-10 index [number of publications with >= 10 citations], and h-index [number of publications h with >= h citations each]). The outcome variable was current academic rank (instructor, assistant professor, associate professor, professor, or endowed professor). Descriptive, bivariate, and multiple regression statistics were computed to evaluate associations between the predictors and academic rank. Receiver-operator characteristic curves were computed to identify thresholds for academic promotion. The sample consisted of 324 academic oral and maxillofacial surgeons, of whom 11.7% were female, 40% had medical degrees, and 8% had research doctorates. The h-index was the most strongly correlated with academic rank (rho=0.62, p<0.001). H-indexes of >= 4, >= 8, and >= 13 were identified as thresholds for promotion to associate professor, professor, and endowed professor, respectively (p<0.001). This study found that the h-index was strongly correlated with academic rank among oral and maxillofacial surgery faculty members and thus suggests that promotions committees should consider using the h-index as an additional method to assess research activity. Dr. Susarla is a Resident, Department of Plastic, Maxillofacial, and Reconstructive Surgery, Johns Hopkins Hospital; Dr. Dodson is Professor of Oral and Maxillofacial Surgery, University of Washington School of Dentistry; Dr. Lopez is a Resident, Department of Plastic, Maxillofacial, and Reconstructive Surgery, Johns Hopkins Hospital; Dr. Swanson is a Resident, Department of Plastic, Maxillofacial, and Reconstructive Surgery, Johns Hopkins Hospital; Mr. Calotta is a candidate for Doctor of Medicine, Johns Hopkins University School of Medicine; and Dr. Peacock is Assistant Professor of Oral and Maxillofacial Surgery, Massachusetts General Hospital and Harvard School of Dental Medicine. Direct correspondence to Dr. Srinivas Susarla, Department of Plastic, Maxillofacial, and Reconstructive Surgery, Johns Hopkins Hospital, 801 N. Caroline Street, JHOC 8, Baltimore, MD 21287; 410-955-5000; ssusarll@jhmi.edu. C1 [Susarla, Srinivas M.; Lopez, Joseph; Swanson, Edward W.] Johns Hopkins Univ Hosp, Dept Plast Maxillofacial & Reconstruct Surg, Baltimore, MD 21287 USA. [Dodson, Thomas B.] Univ Washington, Sch Dent, Oral & Maxillofacial Surg, Seattle, WA 98195 USA. [Calotta, Nicholas] Johns Hopkins Univ Hosp, Sch Med, Doctor Med, Baltimore, MD 21287 USA. [Peacock, Zachary S.] Massachusetts Gen Hosp, Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Peacock, Zachary S.] Harvard Univ, Sch Dent Med, Cambridge, MA 02138 USA. RP Susarla, SM (reprint author), Johns Hopkins Univ Hosp, Dept Plast Maxillofacial & Reconstruct Surg, 801 N Caroline St,JHOC 8, Baltimore, MD 21287 USA. EM ssusarll@jhmi.edu NR 24 TC 3 Z9 3 U1 0 U2 6 PU AMER DENTAL EDUCATION ASSOC-ADEA PI WASHINGTON PA 655 K STREET NW, SUITE 800, WASHINGTON, DC 20001 USA SN 0022-0337 EI 1930-7837 J9 J DENT EDUC JI J. Dent. Educ. PD AUG PY 2015 VL 79 IS 8 BP 907 EP 913 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CO3CN UT WOS:000359034300004 PM 26246528 ER PT J AU Ojha, S Setlur, J Bunting, G Hartnick, CJ AF Ojha, S. Setlur, J. Bunting, G. Hartnick, C. J. TI Managing dysphonia in paediatric patients with complex airway conditions SO JOURNAL OF LARYNGOLOGY AND OTOLOGY LA English DT Article DE Dysphonia; Child; Voice Disorders; Algorithm; Laryngoscopy ID LARYNGOTRACHEAL STENOSIS; VOICE OUTCOMES; RECONSTRUCTION; QUALITY AB Objective: To suggest a phonosurgical management strategy that can be used for children who have previously undergone laryngotracheal reconstruction. Methods: This cases series describes three children who presented with complex, multi-level airway stenosis and marked dysphonia. Phonosurgical intervention involved endoscopic and open approaches, and was combined with voice therapy. A phonosurgical reconstruction management algorithm is suggested for evaluating and treating these complex conditions. Results: Pre-operative assessment is critical, and should involve voice analysis and glottal anatomy assessment using office laryngoscopy and stroboscopy. The risks must be weighed up against the benefit of vocal improvement. Surgical intervention should involve combined endoscopic and open approaches. Conclusion: Voice restoration after paediatric airway reconstruction is a complex challenge. Surgical intervention should be conducted in a step-by-step manner to reduce the risk of worsening dysphonia and airway compromise. The risks and benefits must be carefully explored and discussed. C1 [Ojha, S.] Royal Natl Throat Nose & Ear Hosp, London WC1X 8DA, England. [Setlur, J.; Hartnick, C. J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Bunting, G.] Massachusetts Gen Hosp, Dept Speech Language & Swallowing Disorders, Boston, MA 02114 USA. RP Ojha, S (reprint author), 194 Bromyard Ave, London W3 7FN, England. EM shilpaojha4@gmail.com NR 10 TC 1 Z9 1 U1 0 U2 2 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 2015 VL 129 IS 8 BP 820 EP 824 DI 10.1017/S0022215115001553 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA CO6KA UT WOS:000359264400017 PM 26080854 ER PT J AU Lin, AC Lin, DT AF Lin, Alice C. Lin, Derrick T. TI Reconstruction of Lateral Skull Base Defects with Radial Forearm Free Flaps: The Double-Layer Technique SO JOURNAL OF NEUROLOGICAL SURGERY PART B-SKULL BASE LA English DT Article DE lateral temporal bone; microvascular reconstruction; radial forearm free flap ID FREE TISSUE TRANSFER; TEMPORAL BONE; ANTEROLATERAL THIGH AB IntroductionThe radial forearm flap has fallen out of favor in lateral skull base reconstruction in recent literature. However, especially when used in a double layer, a radial forearm may be able to provide the thickness of a large flap while taking advantage of the pliability for which the flap is renowned. ObjectiveTo report the results of the double-layer technique of radial forearm free flap reconstruction of lateral temporal bone defects. DesignA retrospective chart review. SettingA tertiary care institution. ParticipantsAll consecutive patients who underwent lateral temporal bone resections and were reconstructed with free flaps from 2006 to 2012. Major Outcome MeasuresFlap success rate, complications, and rate of revision surgery. ResultsA total of 17 patients were identified with free flap reconstruction of the lateral skull base. Seven received reconstruction with a double-layer radial forearm flap. Reconstruction-related complications in this group included one case of facial cellulitis. The flap success rate was 100%. These results were comparable with patients who had other flaps. ConclusionsThe radial forearm free flap may be an effective reconstruction option for lateral temporal bone defects especially when used in the double-layer technique. C1 [Lin, Alice C.; Lin, Derrick T.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Lin, Alice C.; Lin, Derrick T.] Harvard Univ, Sch Med, Boston, MA USA. RP Lin, AC (reprint author), Suny Downstate Med Ctr, Dept Otolaryngol, 450 Clarkson Ave,Box 126, Brooklyn, NY 11203 USA. EM Alice.Lin@downstate.edu NR 13 TC 0 Z9 0 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 2193-6331 EI 2193-634X J9 J NEUROL SURG PART B JI Journal of Neurol. Surg. Part B PD AUG PY 2015 VL 76 IS 4 BP 257 EP 261 DI 10.1055/s-0035-1548551 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA CN8DT UT WOS:000358668800003 PM 26225312 ER PT J AU Raghavan, D Lee, TC Curtin, HD AF Raghavan, Deepak Lee, Thomas C. Curtin, Hugh D. TI Cholesterol Granuloma of the Petrous Apex: A 5-Year Review of Radiology Reports with Follow-Up of Progression and Treatment SO JOURNAL OF NEUROLOGICAL SURGERY PART B-SKULL BASE LA English DT Article DE cholesterol granuloma; review; stability; aspiration; embolization ID DIAGNOSIS; MANAGEMENT; DRAINAGE AB ObjectivesTo assess the stability and outcomes of patients with cholesterol granulomas at Brigham and Women's Hospital. DesignA retrospective review of neuroradiology magnetic resonance imaging (MRI) studies was performed. The number of newly diagnosed cases of cholesterol granuloma per year was determined. Additional data included age and gender, clinical presentation if applicable, growth on imaging follow-up, and recurrence on postoperative follow-up if applicable. ParticipantsInclusion criteria included patients who underwent MRI studies between January 1, 2009 and July 1, 2013. Upon review of imaging of these patients, 18 patients had findings compatible with cholesterol granuloma. ResultsDuring the study period, an average of three cases of cholesterol granuloma were diagnosed on MRI per year. Three of 18 patients underwent treatment. Two underwent surgery, both of whom demonstrated recurrence on postoperative follow-up imaging. One patient who underwent computed tomography-guided percutaneous aspiration and Gelfoam (Pfizer, New York, United States) embolization had no recurrence on imaging follow-up of up to 23 months. Among the patients who were observed without intervention, growth was identified in only one patient. ConclusionsCholesterol granulomas are a rare entity; however, their appearance on imaging may be greater than previously reported. Most of the lesions demonstrate stability and can be observed. C1 [Raghavan, Deepak; Lee, Thomas C.; Curtin, Hugh D.] Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Curtin, Hugh D.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Lee, TC (reprint author), Harvard Univ, Sch Med, Dept Radiol, Neuroradiol Sect,Brigham & Womens Hosp, 75 Francis St,PBB3,Room 339, Boston, MA 02115 USA. EM tclee@post.harvard.edu NR 16 TC 1 Z9 1 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 2193-6331 EI 2193-634X J9 J NEUROL SURG PART B JI Journal of Neurol. Surg. Part B PD AUG PY 2015 VL 76 IS 4 BP 266 EP 271 DI 10.1055/s-0034-1396600 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA CN8DT UT WOS:000358668800005 PM 26225314 ER PT J AU Nathaniel, JD Garrido, MM Chai, EJ Goldberg, G Goldstein, NE AF Nathaniel, Jeremy D. Garrido, Melissa M. Chai, Emily J. Goldberg, Gabrielle Goldstein, Nathan E. TI Cost Savings Associated With an Inpatient Palliative Care Unit: Results From the First Two Years SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Palliative medicine; palliative care unit; cost savings; cost; longitudinal study ID OF-LIFE CARE; CONSULTATION SERVICE; PROPENSITY SCORES; CANCER CARE; OUTCOMES; IMPACT AB Context. Palliative care consultation services (PCCS) decrease costs for patients by matching treatments received to patients' and families' goals of care. However, few studies have examined the costs of a specialized palliative care unit (PCU). Objectives. To quantitatively describe Mount Sinai Hospital's PCU's first two years of operation; to examine how patient-related costs changed in the days before and after transfer to PCU; and to compare cost savings of PCU to those of PCCS. Methods. Cost and administrative data from PCU patients from the first 24.5 months of our PCU's operation were analyzed. To compare costs between PCU and PCCS patients, we matched PCU patients to similar PCCS patients and used propensity scores to adjust for differences across groups. Results. The PCU admitted 1107 patients in its first 24.5 months. Over this time frame, there was a statistically significant (P < 0.001) decrease in average daily direct costs per patient. The mean of patients' average cost per day was $687 less while on the PCU than before transfer to PCU. Among patients who died in the hospital, average daily direct cost per patient in the days after transfer to PCU was $240 lower as compared with patients being followed by PCCS on the general hospital wards (SE = $45, P < 0.001). Conclusion. Among patients who died in the hospital, transfer to a PCU is associated with significant cost savings as compared with patients on hospital wards who are seen by a PCCS. Published by Elsevier Inc. on behalf of American Academy of Hospice and Palliative Medicine. C1 [Nathaniel, Jeremy D.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Garrido, Melissa M.; Goldstein, Nathan E.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Garrido, Melissa M.; Chai, Emily J.; Goldstein, Nathan E.] Icahn Sch Med Mt Sinai, Lilian & Benjamin Hertzberg Palliat Care Inst, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Goldberg, Gabrielle] Hofstra North Shore LIJ Sch Med, Hempstead, NY USA. RP Goldstein, NE (reprint author), Mt Sinai Med Ctr, Dept Geriatr & Palliat Med, One Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. EM nathan.goldstein@mssm.edu FU Medical Student Training in Aging Research (MSTAR) Program through the American Geriatrics Society; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service [CDA 11-201/CDP12-255] FX Mr. Nathaniel is supported by the Medical Student Training in Aging Research (MSTAR) Program through the American Geriatrics Society. Dr. Garrido is supported by CDA 11-201/CDP12-255 from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service. NR 30 TC 5 Z9 5 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD AUG PY 2015 VL 50 IS 2 BP 147 EP 154 DI 10.1016/j.jpainsymman.2015.02.023 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA CO1YL UT WOS:000358952100005 PM 25847851 ER PT J AU Yawn, J Lawrence, LA Carroll, WW Mulligan, JK AF Yawn, James Lawrence, Lauren A. Carroll, William W. Mulligan, Jennifer K. TI Vitamin D for the treatment of respiratory diseases: Is it the end or just the beginning? (vol 148, pg 326, 2015) SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Correction C1 [Yawn, James; Lawrence, Lauren A.; Carroll, William W.; Mulligan, Jennifer K.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Mulligan, Jennifer K.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Mulligan, Jennifer K.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Mulligan, JK (reprint author), 135 Rutledge Ave,MSC 550, Charleston, SC 29425 USA. EM konopa@musc.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD AUG PY 2015 VL 152 BP 193 EP 193 DI 10.1016/j.jsbmb.2015.04.013 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA CN9ZQ UT WOS:000358810100021 ER PT J AU Oliveira, J Ornellas, ACP Zhang, CR Oliveira, LMB Araujo-Santos, T Borges, VM Ventura, LMGB Reis, FJFB Aras, R Fernandes, AM Rosand, J Greenberg, SM Furie, KL Rost, NS AF Oliveira-Filho, Jamary Ornellas, Ana C. P. Zhang, Cathy R. Oliveira, Luciana M. B. Araujo-Santos, Theo Borges, Valeria M. Ventura, Lais M. G. B. Reis, Francisco J. F. B. Aras, Roque Fernandes, Andre M. Rosand, Jonathan Greenberg, Steven M. Furie, Karen L. Rost, Natalia S. TI COX-2 rs20417 Polymorphism Is Associated with Stroke and White Matter Disease SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Acute cerebral infarction; genetics of stroke; magnetic resonance imaging; Chagas disease; cyclooxygenase; prostaglandin E2 ID TRYPANOSOMA-CRUZI INFECTION; ACUTE ISCHEMIC-STROKE; CHAGAS-DISEASE; HYPERINTENSITY VOLUME; ATHEROSCLEROSIS RISK; GENETIC-POLYMORPHISM; CEREBRAL-ISCHEMIA; SUBTYPES; CHINESE; COMMUNITIES AB Background: To investigate the effect of COX-2 polymorphism and its product, prostaglandin E2 (PGE2), on stroke risk in an endemic area for Chagas disease. In a separate cohort, to investigate the effect of COX-2 polymorphisms on the total burden of cerebral white matter disease. Methods: Cases were outpatients with ischemic stroke; controls were stroke-free subjects from 2 outpatient clinics (heart failure and caregivers of a movement disorders clinic). We extracted DNA from total blood to investigate the rs20417 COX-2 polymorphism. Serologic tests (Enzime-linked immunosorbent assay) were performed to confirm Trypanosoma cruzi infection and to quantify PGE2 levels. In the Boston cohort, white matter hyperintensity volume (WMHv) was quantified on the admission brain magnetic resonance images of subjects with ischemic stroke, who also donated DNA for the COX-2 gene region analysis. Results: We studied 44 patients with stroke and 96 controls (46 with heart failure and 50 caregivers) in the Brazilian cohort; and 788 stroke patients (302 cardioembolic and 486 noncardioembolic) in the Boston cohort. In the Brazilian cohort, rs20417 polymorphism was associated with both stroke (P = 5 x 10(-6)) and decreased PGE2 levels (P = 4 x 10(-5)); similarly, Chagas was associated with stroke (P = 4 x 10(-3)) and decreased PGE2 levels (P = 7 x 10(-3)). In the Boston cohort, rs20417 polymorphism was associated with increased WMHv among noncardioembolic (P = .037), but not among cardioembolic stroke patients. Conclusions: Variation in COX-2 gene is associated with both symptomatic and silent brain cerebrovascular disease. This candidate gene region should be tested in population-based samples. C1 [Oliveira-Filho, Jamary; Ornellas, Ana C. P.; Oliveira, Luciana M. B.; Ventura, Lais M. G. B.; Reis, Francisco J. F. B.; Aras, Roque; Fernandes, Andre M.] Univ Fed Bahia, Stroke & Cardiomyopathy Clin, Salvador, BA, Brazil. [Oliveira-Filho, Jamary; Ornellas, Ana C. P.; Oliveira, Luciana M. B.; Ventura, Lais M. G. B.] Brazilian Natl Res Comm CNPq, Inst Nacl Ciencia & Tecnol Doencas Tropicais INC, Salvador, BA, Brazil. [Zhang, Cathy R.; Rosand, Jonathan; Greenberg, Steven M.; Rost, Natalia S.] Massachusetts Gen Hosp, Stroke Div, Boston, MA 02114 USA. [Araujo-Santos, Theo] Univ Fed Oeste Bahia UFOB, Barreiras, Brazil. [Borges, Valeria M.] Oswaldo Cruz Fdn Bahia CPqGM FIOCRUZ BA, Ctr Pesquisas Goncalo Moniz, Salvador, BA, Brazil. [Furie, Karen L.] Brown Univ, Dept Neurol, Providence, RI 02912 USA. RP Oliveira, J (reprint author), Inst Ciencias Saude, Rua Reitor Miguel Calmon,Sala 415, BR-40110100 Salvador, BA, Brazil. EM jamary@mail.harvard.edu OI Borges, Valeria/0000-0002-2775-5409; Araujo-Santos, Theo/0000-0001-9861-6660 FU NIH [R01NS063925]; Brazilian National Committee in Research (CNPq) Productivity Grant FX This work was supported, in part, by NIH grant R01NS063925 and a Brazilian National Committee in Research (CNPq) Productivity Grant (J.O.-F.). NR 30 TC 2 Z9 3 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 EI 1532-8511 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD AUG PY 2015 VL 24 IS 8 BP 1817 EP 1822 DI 10.1016/j.jstrokecerebrovasdis.2015.04.018 PG 6 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CO6XB UT WOS:000359300000029 PM 25957909 ER PT J AU Micali, N Solmi, F Horton, NJ Crosby, RD Eddy, KT Calzo, JP Sonneville, KR Swanson, SA Field, AE AF Micali, Nadia Solmi, Francesca Horton, Nicholas J. Crosby, Ross D. Eddy, Kamryn T. Calzo, Jerel P. Sonneville, Kendrin R. Swanson, Sonja A. Field, Alison E. TI Adolescent Eating Disorders Predict Psychiatric, High-Risk Behaviors and Weight Outcomes in Young Adulthood SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE ALSPAC; eating disorders; outcomes; psychiatric; weight ID WELL-BEING ASSESSMENT; BULIMIA-NERVOSA; SELF-REPORT; FEELINGS QUESTIONNAIRE; INTERNATIONAL SURVEY; ANXIETY DISORDERS; ANOREXIA-NERVOSA; BINGE DRINKING; MENTAL-HEALTH; SHORT MOOD AB Objective: To investigate whether anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), and other specified feeding and eating disorders (OSFED), including purging disorder (PD), subthreshold BN, and BED at ages 14 and 16 years, are prospectively associated with later depression, anxiety disorders, alcohol and substance use, and self-harm. Method: Eating disorders were ascertained at ages 14 and 16 years in 6,140 youth at age 14 (58% of those eligible) and 5,069 at age 16 (52% of those eligible) as part of the prospective Avon Longitudinal Study of Parents and Children (ALSPAC). Outcomes (depression, anxiety disorders, binge drinking, drug use, deliberate self-harm, weight status) were measured using interviews and questionnaires about 2 years after predictors. Generalized estimating equation models adjusting for gender, sociodemographic variables, and prior outcome were used to examine prospective associations between eating disorders and each outcome. Results: All eating disorders were predictive of later anxiety disorders. AN, BN, BED, PD, and OSFED were prospectively associated with depression (respectively AN: odds ratio [OR] = 1.39, 95% CI = 1.00-1.94; BN: OR = 3.39, 95% CI = 1.25-9.20; BED: OR = 2.00, 95% CI = 1.06-3.75; and PD: OR = 2.56, 95% CI = 1.38-4.74). All eating disorders but AN predicted drug use and deliberate self-harm (BN: OR = 5.72, 95% CI = 2.22-14.72; PD: OR = 4.88, 95% CI = 2.78-8.57; subthreshold BN: OR = 3.97, 95% CI = 1.44-10.98; and subthreshold BED: OR = 2.32, 95% CI = 1.43-3.75). Although BED and BN predicted obesity (respectively OR = 3.58, 95% CI = 1.06-12.14 and OR = 6.42, 95% CI = 1.69-24.30), AN was prospectively associated with underweight. Conclusions: Adolescent eating disorders, including subthreshold presentations, predict negative outcomes, including mental health disorders, substance use, deliberate self-harm, and weight outcomes. This study highlights the high public health and clinical burden of eating disorders among adolescents. C1 [Micali, Nadia] UCL, Inst Child Hlth, Child & Adolescent Mental Hlth Palliat Care & Ped, London WC1E 6BT, England. [Micali, Nadia] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Solmi, Francesca] UCL, London WC1E 6BT, England. [Horton, Nicholas J.] Amherst Coll, Amherst, MA 01002 USA. [Crosby, Ross D.] Neuropsychiat Res Inst, Fargo, ND USA. [Crosby, Ross D.] Univ N Dakota, Sch Med & Hlth Sci, Fargo, ND USA. [Eddy, Kamryn T.] Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, Boston, MA 02114 USA. [Eddy, Kamryn T.; Calzo, Jerel P.] Harvard Univ, Sch Med, Boston, MA USA. [Calzo, Jerel P.; Field, Alison E.] Boston Childrens Hosp, Div Adolescent Med, Boston, MA USA. [Sonneville, Kendrin R.] Univ Michigan, Sch Publ Hlth, Human Nutr Program, Ann Arbor, MI 48109 USA. [Swanson, Sonja A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Field, Alison E.] Harvard Univ, Sch Publ Hlth, Sch Med, Boston, MA 02115 USA. [Field, Alison E.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. RP Micali, N (reprint author), UCL Inst Child Hlth, Behav & Brain Sci Unit, Populat Policy & Practice Res Theme, 30 Guilford St, London WC1N 1EH, England. EM n.micali@ucl.ac.uk OI Crosby, Ross/0000-0001-9131-1629; Solmi, Francesca/0000-0003-0219-9503 FU UK Medical Research Council [74882]; Wellcome Trust [076467, 102215/2/13/2]; University of Bristol; National Institute of Health [MH087786, DHCS/08/08/012] FX The UK Medical Research Council (ref:74882), Wellcome Trust (ref:076467, 102215/2/13/2), and University of Bristol provide core support for the Avon Longitudinal Study of Parents and Children (ALSPAC). This research was funded by a National Institute of Health grant to Drs. Field and Micali (MH087786), and a National Institute of Health Research clinician scientist award to Dr. Micali (DHCS/08/08/012). NR 54 TC 11 Z9 11 U1 2 U2 59 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 EI 1527-5418 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD AUG PY 2015 VL 54 IS 8 BP 652 EP 659 DI 10.1016/j.jaac.2015.05.009 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA CO2GR UT WOS:000358974700008 PM 26210334 ER PT J AU Jackson, PR AF Jackson, Peter R. TI Peace Like a River SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [Jackson, Peter R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jackson, Peter R.] McLean Hosp, Boston, MA USA. [Jackson, Peter R.] Harvard Univ, Sch Med, Boston, MA USA. RP Jackson, PR (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM prjackson@partners.org NR 1 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 EI 1527-5418 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD AUG PY 2015 VL 54 IS 8 BP 690 EP 691 DI 10.1016/j.jaac.2015.06.008 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA CO2GR UT WOS:000358974700016 ER PT J AU Lorenz, JM Al-Refaie, WB Cash, BD Gaba, RC Gervais, DAA Gipson, MG Kolbeck, KJ Kouri, BE Marshalleck, FE Nair, AV Ray, CE Hohenwalter, EJ AF Lorenz, Jonathan M. Al-Refaie, Waddah B. Cash, Brooks D. Gaba, Ron C. Gervais, Debr A. A. Gipson, Matthew G. Kolbeck, Kenneth J. Kouri, Brian E. Marshalleck, Francis E. Nair, Ajit V. Ray, Charles E., Jr. Hohenwalter, Eric J. TI ACR Appropriateness Criteria Radio logic Management of Infected Fluid Collections SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Appropriateness Criteria; infected fluid; abscess; percutaneous; endoscopic; drainage ID ULTRASOUND-GUIDED DRAINAGE; MALIGNANT PLEURAL EFFUSIONS; PYOGENIC LIVER-ABSCESS; DEEP PELVIC ABSCESSES; PERCUTANEOUS DRAINAGE; PANCREATIC ABSCESSES; INTRAABDOMINAL ABSCESS; TUBOOVARIAN ABSCESS; ABDOMINAL ABSCESSES; SPLENIC ABSCESS AB The best management of infected fluid collections depends on a careful assessment of clinical and anatomic factors as well as an up-to-date review of the published literature, to be able to select from a host of multidisciplinary treatment options. This article reviews conservative, radiologic, endoscopic, and surgical options and their best application to infected fluid collections as determined by the ACR Appropriateness Criteria Expert Panel on Interventional Radiology. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals, and the application, by the panel, of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. C1 [Lorenz, Jonathan M.] Univ Chicago Hosp, Chicago, IL 60637 USA. [Al-Refaie, Waddah B.] Georgetown Univ Hosp, Washington, DC 20007 USA. [Al-Refaie, Waddah B.] Amer Coll Surg, Chicago, IL USA. [Cash, Brooks D.] Univ S Alabama, Mobile, AL 36688 USA. [Cash, Brooks D.] Amer Gastroenterol Assoc, Bethesda, MD USA. [Gaba, Ron C.] Univ Illinois Hosp, Chicago, IL USA. [Gervais, Debr A. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gipson, Matthew G.; Ray, Charles E., Jr.] Univ Colorado, Aurora, CO USA. [Kolbeck, Kenneth J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Kouri, Brian E.] Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 USA. [Marshalleck, Francis E.] James Whitcomb Riley Hosp Children, Indianapolis, IN 46202 USA. [Nair, Ajit V.] Santa Clara Valley Med Ctr, San Jose, CA 95128 USA. [Hohenwalter, Eric J.] Froedtert, Milwaukee, WI USA. [Hohenwalter, Eric J.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. RP Lorenz, JM (reprint author), Univ Chicago Hosp, Dept Radiol, 5841 S Maryland Ave MC 2026, Chicago, IL 60637 USA. EM jlorenz@radiology.bsd.uchicago.edu NR 72 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD AUG PY 2015 VL 12 IS 8 BP 791 EP 799 DI 10.1016/j.jacr.2015.04.025 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CO5CK UT WOS:000359177000011 PM 26145248 ER PT J AU Boland, GW Duszak, R AF Boland, Giles W. Duszak, Richard, Jr. TI Protocol Management and Design: Current and Future Best Practices SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Boland, Giles W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Boland, GW (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. EM gboland@partners.org RI Duszak, Richard/L-1811-2016 OI Duszak, Richard/0000-0003-0425-3008 NR 1 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD AUG PY 2015 VL 12 IS 8 BP 833 EP 835 DI 10.1016/j.jacr.2015.04.021 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CO5CK UT WOS:000359177000018 PM 26250976 ER PT J AU Rehwald, CM Tripathy, A Bhargava, P AF Rehwald, Christine M. Tripathy, Arindam Bhargava, Puneet TI Systems Redesign: A Quality Improvement Initiative at a Tertiary-Care Veterans Affairs Medical Center SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Rehwald, Christine M.; Bhargava, Puneet] Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA. [Rehwald, Christine M.; Bhargava, Puneet] Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Diagnost Imaging Serv, Seattle, WA 98108 USA. [Tripathy, Arindam] Univ Washington, Milgard Sch Business, Tacoma, WA USA. RP Bhargava, P (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Mail Box 358280,S-114 Radiol,1660 S Columbian Way, Seattle, WA 98108 USA. EM bhargp@uw.edu NR 8 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD AUG PY 2015 VL 12 IS 8 BP 842 EP 844 DI 10.1016/j.jacr.2015.01.020 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CO5CK UT WOS:000359177000021 PM 25841865 ER PT J AU O'Brien, KM Stolz, LA Amini, R Gross, A Stolz, U Adhikari, S AF O'Brien, Kathleen M. Stolz, Lori A. Amini, Richard Gross, Austin Stolz, Uwe Adhikari, Srikar TI Focused Assessment With Sonography for Trauma Examination SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE bedside ultrasound; emergency ultrasound; focused assessment with sonography for trauma; free fluid; left upper quadrant view; splenorenal ID ABDOMINAL-TRAUMA; ULTRASONOGRAPHY; HEMOPERITONEUM; ULTRASOUND; UTILITY AB Objectives The purpose of this study was to determine the frequency and predominant location of isolated free fluid in the left upper quadrant (LUQ) on focused assessment with sonography for trauma (FAST) examinations of adult patients with trauma presenting to the emergency department. Methods-We conducted a retrospective review of adult patients with positive FAST results for free fluid in the abdomen at 2 academic emergency departments. Eligible FAST examinations were reviewed for the presence of fluid in the LUQ and exact location of free fluid within the LUQ. Results-A total of 100 FAST examinations with free fluid in the abdomen that met inclusion criteria were identified during the study period. Overall 32 of 100 (32%; 95% confidence interval [CI], 23.5%-41.6%) of patients with positive FAST results were found to have free fluid in the LUQ, Only 6 of 100(6%; 95% CI, 2.5%-11.9%) patients with positive FAST results had free fluid isolated to the LUQ, Of these 6 patients with isolated LUQ free fluid, none had free fluid isolated to the splenorenal fossa alone; 1 had free fluid isolated to the subpbrenic space (above the spleen/below the diaphragm); and 4 had free fluid visible only in the left paracolic gutter/inferior to the spleen. Twenty-seven of 32 patients (84%; 95% CI, 69.1%-93.8%) with free fluid anywhere in the LUQ were also found to have fluid in the left paracolic gutter. Conclusions-Free fluid isolated to the LUQ occurs in a clinically significant number of adult patients with trauma and positive FAST results. Isolated fluid accumulation was often seen within the left paracolic gutter. C1 [O'Brien, Kathleen M.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Stolz, Lori A.; Amini, Richard; Gross, Austin; Stolz, Uwe; Adhikari, Srikar] Univ Arizona, Med Ctr, Dept Emergency Med, Tucson, AZ 85724 USA. RP Adhikari, S (reprint author), Univ Arizona, Med Ctr, Dept Emergency Med, POB 245057, Tucson, AZ 85724 USA. EM sriadhikari@aol.com NR 12 TC 0 Z9 0 U1 0 U2 3 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 PY 2015 VL 34 IS 8 BP 1429 EP 1434 DI 10.7863/ultra.34.8.1429 PG 6 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA CO0DB UT WOS:000358819200010 PM 26206829 ER PT J AU Gerber, RE Bromley, B Benson, CB Frates, MC AF Gerber, Rebecca E. Bromley, Bryann Benson, Carol B. Frates, Mary C. TI Sonographic Findings in Fetal Renal Vein Thrombosis SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE fetal sonography; hypercoagulability; inferior vena cava thrombosis; obstetric ultrasound; renal vein thrombosis ID INFERIOR VENA-CAVA; VENOUS THROMBOSIS; ULTRASONIC FEATURES; HYDROPS-FETALIS; IN-UTERO; NEWBORN AB We present the sonographic findings of fetal renal vein thrombosis in a series of 6 patients. The mean gestational age at diagnosis was 31.2 weeks. Four cases were unilateral, and 2 were bilateral. The most common findings were renal enlargement and intrarenal vascular calcifications, followed by increased renal parenchymal echogenicity. Inferior vena cava thrombosis was found in 4 patients and common iliac vein thrombosis in 2. Fetal renal vein thrombosis is an uncommon diagnosis with characteristic sonographic findings. The presence of these findings should prompt Doppler interrogation of the renal vein and inferior vena cava to confirm the diagnosis. C1 [Gerber, Rebecca E.; Benson, Carol B.; Frates, Mary C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Bromley, Bryann] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Bromley, Bryann] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. RP Frates, MC (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM mfrates@partners.org NR 28 TC 0 Z9 0 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 EI 1550-9613 J9 J ULTRAS MED JI J. Ultrasound Med. PD AUG PY 2015 VL 34 IS 8 BP 1509 EP 1514 DI 10.7863/ultra.34.8.1509 PG 6 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA CO0DB UT WOS:000358819200020 PM 26206839 ER PT J AU Ge, BH Weber, CN Wildenberg, JC Nadolski, GJ Gade, TP Hunt, SJ Soulen, MC Itkin, M AF Ge, Benjamin H. Weber, Charles N. Wildenberg, Joseph C. Nadolski, Gregory J. Gade, Terence P. Hunt, Stephen J. Soulen, Michael C. Itkin, Maxim TI Magnetic Resonance-Monitored Coaxial Electrochemical Ablation-Preliminary Evaluation of Technical Feasibility SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID ELECTRICAL-CURRENT THERAPY; EX-VIVO; ELECTROLYTIC ABLATION; HEPATIC METASTASES; LOCAL TREATMENT; MR THERMOMETRY; LIVER; TUMORS; MODEL; RAT AB Purpose: To evaluate the technical feasibility of a coaxial electrode configuration to rapidly create a mechanically defined electrochemical ablation zone monitored by magnetic resonance (MR) imaging in real time. Materials and Methods: A direct current generator supplied the nitinol cathode cage and central platinum anode for coaxial electrochemical ablation. Safety and efficacy were evaluated by measuring local pH, temperature, and current scatter in saline solutions. Ablation zone diameters of 3-6 cm (n = 72) were created on ex vivo bovine liver and verified by gross pathology. Feasibility of MR monitoring was evaluated using 8 swine livers to create ablations of 3 cm (n = 12), 4 cm (n = 4), and 5 cm (n = 4) verified by histology. Results: Local pH was 3.2 at the anode and 13.8 at the cathode. Current scatter was negligible. Ablation progress increased relative to local ion concentration, and MR signal changes corresponded to histologic findings. In the ex vivo model, the times to achieve complete ablation were 15 minutes, 20 minutes, 35 minutes, and 40 minutes for diameters of 3 cm, 4 cm, 5 cm, and 6 cm, respectively. Ablation times for the in situ model were 15 minutes, 35 minutes, and 50 minutes for 3 cm, 4 cm, and 5 cm, respectively. Conclusions: The coaxial configuration mechanically defined the electrochemical ablation zone with times similar to comparably sized thermal ablations. MR compatibility allowed for real-time monitoring of ablation progress. C1 [Ge, Benjamin H.; Weber, Charles N.; Wildenberg, Joseph C.; Nadolski, Gregory J.; Gade, Terence P.; Hunt, Stephen J.; Soulen, Michael C.; Itkin, Maxim] Hosp Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Ge, Benjamin H.; Weber, Charles N.; Wildenberg, Joseph C.; Nadolski, Gregory J.; Gade, Terence P.; Hunt, Stephen J.; Itkin, Maxim] Hosp Univ Penn, Penn Image Guided Intervent Lab, Philadelphia, PA 19104 USA. [Itkin, Maxim] Philadelphia Vet Affairs Med Ctr, Dept Radiol, Philadelphia, PA USA. RP Ge, BH (reprint author), Hosp Univ Penn, Dept Radiol, 3400 Spruce St, Philadelphia, PA 19104 USA. EM ge.benjamin@gmail.com OI Wildenberg, Joe/0000-0001-5489-8467 FU T32 Training Grant; University of Pennsylvania Institute of Translational Medicine and Therapeutics; CareFusion; SIR Foundation; National Center for Research Resources [UL1RR024134]; National Center for Advancing Translational Sciences [UL1TR000003]; Radiological Society of North America; Guerbet LLC; BTG; Merit Medical; Sirtex Medical; Cambridge University Press FX B.H.G., C.N.W., and M.I. have patent ownership or part ownership of a coaxial probe ablation device developed as a result of these experiments with a preliminary patent filing in progress. C.N.W. received funding from a T32 Training Grant and University of Pennsylvania Institute of Translational Medicine and Therapeutics for research outside of the submitted work. G.J.N. is a paid consultant for CareFusion for work outside of the submitted work. T.P.G. received funding from the SIR Foundation, National Center for Research Resources Grant No. UL1RR024134, National Center for Advancing Translational Sciences Grant No. UL1TR000003, Radiological Society of North America, T32 Training Grant, and Guerbet LLC for research outside of the submitted work. S.J.H. received funding from a T32 Training Grant and SIR Foundation Pilot Grant for research outside of the submitted work. M.C.S. is a paid consultant for, and received funding from, Guerbet LLC, BTG, Merit Medical, Sirtex Medical, and Cambridge University Press for research and work outside of the submitted work. The other author has not identified a conflict of interest. NR 29 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 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD AUG PY 2015 VL 26 IS 8 BP 1238 EP 1246 DI 10.1016/j.jvir.2015.05.015 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA CO3YP UT WOS:000359097500023 PM 26210247 ER PT J AU Deipolyi, AR Oklu, R Al-Ansari, S Ganguli, S AF Deipolyi, Amy R. Oklu, Rahmi Al-Ansari, Shehab Ganguli, Suvranu TI Re: Safety and Efficacy of 70-150 mu m and 100-300 mu m Drug-Eluting Bead Transarterial Chemoembolization for Hepatocellular Carcinoma Response SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Letter ID HEPATIC CHEMOEMBOLIZATION; LIVER; COMPLICATIONS; THERAPY; TUMORS C1 [Deipolyi, Amy R.] NYU, Med Ctr, Dept Radiol, Div Vasc & Intervent Radiol, New York, NY 10016 USA. [Oklu, Rahmi; Al-Ansari, Shehab; Ganguli, Suvranu] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Sect Intervent Radiol,Dept Radiol, Boston, MA USA. RP Deipolyi, AR (reprint author), NYU, Med Ctr, Dept Radiol, Div Vasc & Intervent Radiol, New York, NY 10016 USA. OI Deipolyi, Amy/0000-0003-3144-386X NR 9 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 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD AUG PY 2015 VL 26 IS 8 BP 1251 EP 1252 DI 10.1016/j.jvir.2015.05.016 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA CO3YP UT WOS:000359097500028 PM 26210252 ER PT J AU Pascoe, S Locantore, N Dransfield, MT Barnes, NC Pavord, I AF Pascoe, Steven Locantore, Nicholas Dransfield, Mark T. Barnes, Neil C. Pavord, Ian TI Blood eosinophil counts as markers of response to inhaled corticosteroids in COPD? Reply SO LANCET RESPIRATORY MEDICINE LA English DT Letter ID OBSTRUCTIVE PULMONARY-DISEASE; EXACERBATIONS C1 [Pascoe, Steven; Locantore, Nicholas] GlaxoSmithKline, Res Triangle Pk, NC 27709 USA. [Dransfield, Mark T.] Univ Alabama Birmingham, Lung Hlth Ctr, Birmingham, AL USA. [Dransfield, Mark T.] Birmingham VA Med Ctr, Birmingham, AL USA. [Barnes, Neil C.] GlaxoSmithKline, Uxbridge, Middx, England. [Barnes, Neil C.] Barts & London Queen Marys Sch Med & Dent, William Harvey Inst, London, England. [Pavord, Ian] Univ Oxford, Nuffield Dept Clin Med, Resp Med Unit, Oxford OX1 2JD, England. RP Pascoe, S (reprint author), GlaxoSmithKline, Res Triangle Pk, NC 27709 USA. EM steven.j.pascoe@gsk.com NR 10 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 2213-2600 J9 LANCET RESP MED JI Lancet Resp. Med. PD AUG PY 2015 VL 3 IS 8 BP E27 EP E27 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CO2AE UT WOS:000358956800005 PM 26282479 ER PT J AU Sabino, CP Garcez, AS Nunez, SC Ribeiro, MS Hamblin, MR AF Sabino, C. P. Garcez, A. S. Nunez, S. C. Ribeiro, M. S. Hamblin, M. R. TI Real-time evaluation of two light delivery systems for photodynamic disinfection of Candida albicans biofilm in curved root canals SO LASERS IN MEDICAL SCIENCE LA English DT Article DE Photoinactivation; Photoactivated; Diffuser optical fiber; Molar; Fungi; Yeast; Bioluminescence ID CONVENTIONAL ENDODONTIC TREATMENT; IN-VITRO; ENTEROCOCCUS-FAECALIS; METHYLENE-BLUE; OPTICAL-FIBER; LASER-LIGHT; THERAPY; INFECTIONS; INACTIVATION; MECHANISMS AB Antimicrobial photodynamic therapy (APDT) combined with endodontic treatment has been recognized as an alternative approach to complement conventional root canal disinfection methods on bacterial biofilms. We developed an in vitro model of bioluminescent Candida albicans biofilm inside curved dental root canals and investigated the microbial reduction produced when different light delivery methods are employed. Each light delivery method was evaluated in respect to the light distribution provided inside curved root canals. After conventional endodontic preparation, teeth were sterilized before canals were contaminated by a bioluminescent strain of C. albicans (CEC789). Methylene blue (90 mu M) was introduced into the canals and then irradiated (lambda = 660 nm, P = 100 mW, beam diameter = 2 mm) with laser tip either in contact with pulp chamber or within the canal using an optical diffuser fiber. Light distribution was evaluated by CCD camera, and microbial reduction was monitored through bioluminescence imaging. Our findings demonstrated that the bioluminescent C. albicans biofilm model had good reproducibility and uniformity. Light distribution in dental tissue was markedly dependent on the light delivery system, and this strategy was directly related to microbial destruction. Both light delivery systems performed significant fungal inactivation. However, when irradiation was performed with optical diffuser fiber, microbial burden reduction was nearly 100 times more effective. Bioluminescence is an interesting real-time analysis to endodontic C. albicans biofilm inactivation. APDT showed to be an effective way to inactivate C. albicans biofilms. Diffuser fibers provided optimized light distribution inside curved root canals and significantly increased APDT efficiency. C1 [Sabino, C. P.; Nunez, S. C.; Ribeiro, M. S.] IPEN CNEN SP, Ctr Lasers & Applicat, Sao Paulo, Brazil. [Sabino, C. P.; Hamblin, M. R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Garcez, A. S.] Sao Leopoldo Mand Dent Res Ctr, Campinas, SP, Brazil. [Hamblin, M. R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, M. R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. RP Ribeiro, MS (reprint author), IPEN CNEN SP, Ctr Lasers & Applicat, Sao Paulo, Brazil. EM marthasr@usp.br RI Ribeiro, Martha/G-3517-2012; Sabino, Caetano/K-8356-2013; Sabino, Caetano/D-4196-2016; Nunez, Silvia/C-7241-2017; OI Ribeiro, Martha/0000-0002-4203-1134; Sabino, Caetano/0000-0002-2048-2823; Nunez, Silvia/0000-0003-2101-8333; Hamblin, Michael/0000-0001-6431-4605 FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2010/13313-9]; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq); US National Institutes of Health [NIH R01AI050875] FX This work was supported by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, grant 2010/13313-9) and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq). MR Hamblin was supported by the US National Institutes of Health (NIH R01AI050875). The authors gratefully recognize J. Chibebe Junior (Department of Biosciences and Oral Diagnosis, Univ Estadual Paulista/UNESP, Sao Jose dos Campos, SP 12245-000, Brazil) for the experimental assistance and Christophe d'Enfert (Unite Biologie et Pathogenicite Fongiques, F-75015 Paris, France) for providing the luciferase-expressing strain of C. albicans. NR 47 TC 7 Z9 8 U1 0 U2 7 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0268-8921 EI 1435-604X J9 LASER MED SCI JI Lasers Med. Sci. PD AUG PY 2015 VL 30 IS 6 BP 1657 EP 1665 DI 10.1007/s10103-014-1629-x PG 9 WC Engineering, Biomedical; Surgery SC Engineering; Surgery GA CO4NV UT WOS:000359138500004 PM 25060900 ER PT J AU Regestein, Q Friebely, J Schiff, I AF Regestein, Quentin Friebely, Joan Schiff, Isaac TI How self-reported hot flashes may relate to affect, cognitive performance and sleep SO MATURITAS LA English DT Article DE Cognition; Hot flashes; Menopause; Mid life women; Psychological symptoms; Sleep ID HORMONE-REPLACEMENT THERAPY; MIDDLE-AGED WOMEN; QUALITY-OF-LIFE; POSTMENOPAUSAL WOMEN; MENOPAUSAL TRANSITION; CLIMACTERIC COMPLAINTS; DEPRESSIVE SYMPTOMS; CIRCADIAN-RHYTHMS; COMMUNITY SURVEY; ESTROGEN-LEVELS AB Purpose: To explain the controversy about whether midlife women who self-report hot flashes have relatively increased affective symptoms, poor cognitive performance or worse sleep. Methods: Retrospective data from 88 women seeking relief from bothersome day and night hot flashes were submitted to mixed linear regression modeling to find if estimated hot flashes, as measured by Women's Health Questionnaire (WHQ) items, or diary-documented hot flashes recorded daily, were associated with each other, or with affective, cognitive or sleep measures. Results: Subjects averaged 6.3 daytime diary-documented hot flashes and 2.4 nighttime diary-documented hot flashes per 24 h. Confounder-controlled diary-documented hot flashes but not estimated hot flashes were associated with increased Leeds anxiety scores (F=4.9; t=2.8; p=0.01) and Leeds depression scores (3.4; 2.5; 0.02), decreased Stroop Color Word test performance (9.4; 3.5; 0.001), increased subjective sleep disturbance (effect size = 0.83) and increased objective sleep disturbance (effect size = 035). Hot flash effects were small to moderate in size. Univariate but not multivariate analyses revealed that all hot flash measures were associated with all affect measures. Different measures of hot flashes associated differently with affect, cognition and sleep. Only nighttime diary-document hot flash consistently correlated with any affect measures in multivariate analyses. Conclusions: The use of differing measures for hot flashes, affect, cognition and sleep may account for the continually reported inconsistencies in menopause study outcomes. This problem impedes forging a consensus on whether hot flashes correlate with neuropsychological symptoms. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Regestein, Quentin; Friebely, Joan] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Schiff, Isaac] Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Regestein, Q (reprint author), Brigham & Womens Hosp, Dept Psychiat, 75 Francis St, Boston, MA 02115 USA. EM gregestein@partners.org FU Brigham and Women's Hospital internal research funds FX Brigham and Women's Hospital internal research funds supported this study. NR 76 TC 2 Z9 3 U1 6 U2 11 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-5122 EI 1873-4111 J9 MATURITAS JI Maturitas PD AUG PY 2015 VL 81 IS 4 BP 449 EP 455 DI 10.1016/j.maturitas.2015.05.005 PG 7 WC Geriatrics & Gerontology; Obstetrics & Gynecology SC Geriatrics & Gerontology; Obstetrics & Gynecology GA CO5BX UT WOS:000359175700008 PM 26074034 ER PT J AU Tefferi, A Rajkumar, SV Gertz, MA Kyle, RA Kantarjian, H Allison, J Bast, RC Cortes, J Fidler, IJ Freireich, E Gutterman, J Hong, WK Hortobagyi, GN Mendelsohn, J Strong, LC Ueno, NT LeMaistre, CA Baker, LH Lawrence, TS Abkowitz, JL Deeg, HJ Estey, E Lyman, GH Adamson, JW Advani, RH Coutre, S Greenberg, P Link, MP Rosenberg, SA Antman, KH Bennett, JM Benz, EJ Canellos, GP Daley, GQ DeAngelo, DJ Fuchs, C Handin, RI Kantoff, PW Steensma, DP Stone, R Winer, EP Berliner, N Handin, RI Bertino, J Bhatia, R Bhatia, S Erba, HP Bhojwani, D Blanke, CD Bloomfield, CD Byrd, JC Pollock, R Bosserman, L Forman, S Broxmeyer, HE Einhorn, LH Cabanillas, F Chabner, BA Colon-Otero, G Chanan-Khan, A Foran, J Cheson, B Clarkson, B Giralt, S Hudis, C Levine, R Tallman, MS Younes, A Zelenetz, AD Cohn, SL Golomb, H Hellman, S Larson, RA Stock, W Cristofanilli, M Curran, WJ Khuri, FR Lonial, S Daley, GQ Deeg, HJ Lyman, GH Press, O Radich, J Sandmaier, BM Stone, R Esteva, FJ George, JN Hoff, PM Hoffman, R Horowitz, M Issa, JP Johnson, BE Kaushansky, K Khayat, D Kipps, TJ Lippman, SM Kripke, M Markman, M Neropol, NJ Messinger, Y Mulvey, TM O'Brien, S Van Etten, RA Perez-Soler, R Prchal, J Rai, K Rowe, JM Rugo, H Runowicz, CD Saven, A Silver, RT Schafer, AI Schiffer, C Sekeres, MA Siu, LL Stewart, FM Thompson, M Vose, JM Wiernik, PH AF Tefferi, Ayalew Rajkumar, S. Vincent Gertz, Morie A. Kyle, Robert A. Kantarjian, Hagop Allison, James Bast, Robert C., Jr. Cortes, Jorge Fidler, Isaiah J. Freireich, Emil Gutterman, Jordan Hong, Waun Ki Hortobagyi, Gabriel N. Mendelsohn, John Strong, Louise C. Ueno, Naoto T. LeMaistre, Charles A. Baker, Lawrence H. Lawrence, Theodore S. Abkowitz, Jan L. Deeg, H. Joachim Estey, Elihu Lyman, Gary H. Adamson, John W. Advani, Ranjana Hira Coutre, Steven Greenberg, Peter Link, Michael P. Rosenberg, Saul A. Antman, Karen H. Bennett, John M. Benz, Edward J., Jr. Canellos, George Peter Daley, George Q. DeAngelo, Daniel J. Fuchs, Charles Handin, Robert I. Kantoff, Philip W. Steensma, David P. Stone, Richard Winer, Eric P. Berliner, Nancy Handin, Robert I. Bertino, Joseph Bhatia, Ravi Bhatia, Smita Erba, Harry P. Bhojwani, Deepa Blanke, Charles D. Bloomfield, Clara D. Byrd, John C. Pollock, Raphael Bosserman, Linda Forman, Stephen Broxmeyer, Hal E. Einhorn, Lawrence H. Cabanillas, Fernando Chabner, Bruce A. Colon-Otero, Gerardo Chanan-Khan, Asher Foran, James Cheson, Bruce Clarkson, Bayard Giralt, Sergio Hudis, Clifford Levine, Ross Tallman, Martin S. Younes, Anas Zelenetz, Andrew D. Cohn, Susan L. Golomb, Harvey Hellman, Samuel Larson, Richard A. Stock, Wendy Cristofanilli, Massimo Curran, Walter J., Jr. Khuri, Fadlo R. Lonial, Sagar Daley, George Q. Deeg, H. Joachim Lyman, Gary H. Press, Oliver Radich, Jerald Sandmaier, Brenda M. Stone, Rainer Esteva, Francisco J. George, James N. Hoff, Paulo Marcelo Hoffman, Ronald Horowitz, Mary Issa, Jean Pierre Johnson, Bruce Evan Kaushansky, Kenneth Khayat, David Kipps, Thomas J. Lippman, Scott M. Kripke, Margaret Markman, Maurie Neropol, Neal J. Messinger, Yoav Mulvey, Therese M. O'Brien, Susan Van Etten, Richard A. Perez-Soler, Roman Prchal, Josef Rai, Kanti Rowe, Jacob M. Rugo, Hope Runowicz, Carolyn D. Saven, Alan Silver, Richard T. Schafer, Andrew I. Schiffer, Charles Sekeres, Mikkael A. Siu, Lillian L. Stewart, F. Marc Thompson, Michael Vose, Julie M. Wiernik, Peter H. TI In Support of a Patient-Driven Initiative and Petition to Lower the High Price of Cancer Drugs SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material C1 [Tefferi, Ayalew; Rajkumar, S. Vincent; Gertz, Morie A.; Kyle, Robert A.] Mayo Clin, Rochester, MN USA. [Kantarjian, Hagop; Allison, James; Bast, Robert C., Jr.; Cortes, Jorge; Fidler, Isaiah J.; Freireich, Emil; Gutterman, Jordan; Hong, Waun Ki; Hortobagyi, Gabriel N.; Mendelsohn, John; Strong, Louise C.; Ueno, Naoto T.; LeMaistre, Charles A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Baker, Lawrence H.; Lawrence, Theodore S.] Univ Michigan, Ann Arbor, MI 48109 USA. [Abkowitz, Jan L.; Deeg, H. Joachim; Estey, Elihu; Lyman, Gary H.] Univ Washington, Med Sch, Seattle, WA 98195 USA. [Adamson, John W.] Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA. [Advani, Ranjana Hira; Coutre, Steven; Greenberg, Peter; Link, Michael P.; Rosenberg, Saul A.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Antman, Karen H.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Bennett, John M.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Benz, Edward J., Jr.; Canellos, George Peter; Daley, George Q.; DeAngelo, Daniel J.; Fuchs, Charles; Handin, Robert I.; Kantoff, Philip W.; Steensma, David P.; Stone, Richard; Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Benz, Edward J., Jr.; Canellos, George Peter; Daley, George Q.; DeAngelo, Daniel J.; Fuchs, Charles; Handin, Robert I.; Kantoff, Philip W.; Steensma, David P.; Stone, Richard; Winer, Eric P.] Harvard Univ, Sch Med, Boston, MA USA. [Berliner, Nancy; Handin, Robert I.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bertino, Joseph] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA. [Bhatia, Ravi; Bhatia, Smita; Erba, Harry P.] Univ Alabama Birmingham, Birmingham, AL USA. [Bhojwani, Deepa] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Blanke, Charles D.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Bloomfield, Clara D.; Byrd, John C.; Pollock, Raphael] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Bosserman, Linda; Forman, Stephen] City Hope Med Fdn, Duarte, CA USA. [Broxmeyer, Hal E.; Einhorn, Lawrence H.] Indiana Univ, Sch Med, Indianapolis, IN USA. [Cabanillas, Fernando] Auxilio Canc Ctr, Hato Rey, PR USA. [Chabner, Bruce A.; Colon-Otero, Gerardo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chanan-Khan, Asher; Foran, James] Mayo Clin, Ctr Canc, Jacksonville, FL 32224 USA. [Cheson, Bruce] Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. [Clarkson, Bayard; Giralt, Sergio; Hudis, Clifford; Levine, Ross; Tallman, Martin S.; Younes, Anas; Zelenetz, Andrew D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Cohn, Susan L.; Golomb, Harvey; Hellman, Samuel; Larson, Richard A.; Stock, Wendy] Univ Chicago, Chicago, IL 60637 USA. [Cristofanilli, Massimo] Thomas Jefferson Univ, Sidney Kimmel Canc Ctr, Philadelphia, PA 19107 USA. [Curran, Walter J., Jr.; Khuri, Fadlo R.; Lonial, Sagar] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Daley, George Q.] Boston Childrens Hosp, Boston, MA USA. [Deeg, H. Joachim; Lyman, Gary H.; Press, Oliver; Radich, Jerald; Sandmaier, Brenda M.; Stone, Rainer] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Esteva, Francisco J.] NYU, Langone Med Ctr, New York, NY USA. [George, James N.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Hoff, Paulo Marcelo] Univ Sao Paulo, Sao Paulo, Brazil. [Hoffman, Ronald] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Horowitz, Mary] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Issa, Jean Pierre] Temple Univ, Philadelphia, PA 19122 USA. [Johnson, Bruce Evan] Lowe Ctr Thorac Oncol, Boston, MA USA. [Kaushansky, Kenneth] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Khayat, David] Hop La Pitie Salpetriere, Paris, France. [Kipps, Thomas J.; Lippman, Scott M.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA USA. [Kripke, Margaret] Canc Prevent & Res Inst Texas, Austin, TX USA. [Markman, Maurie] Canc Treatment Ctr Amer, Eastern Reg Med Ctr, Philadelphia, PA USA. [Neropol, Neal J.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Neropol, Neal J.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Messinger, Yoav] Childrens Hosp & Clin Minnesota, Minneapolis, MN USA. [Mulvey, Therese M.] Southcoast Centers Canc Care, Fairhaven, MA USA. [O'Brien, Susan; Van Etten, Richard A.] Univ Calif Irvine, Irvine, CA USA. [Perez-Soler, Roman] Albert Einstein Coll Med, Bronx, NY USA. [Prchal, Josef] Univ Utah, Salt Lake City, UT USA. [Rai, Kanti] North Shore LIJ Canc Inst, New Hyde Pk, NY USA. [Rowe, Jacob M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Rugo, Hope] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Runowicz, Carolyn D.] Florida Int Univ, Herbert Wertheim Coll Med, Miami, FL 33199 USA. [Saven, Alan; Silver, Richard T.] Scripps Clin Med Grp, La Jolla, CA USA. [Schafer, Andrew I.] Weill Cornell Med Coll, New York, NY USA. [Schiffer, Charles] Barbara Ann Karmanos Canc Inst, Detroit, MI USA. [Sekeres, Mikkael A.] Cleveland Clin, Cleveland, OH 44106 USA. [Siu, Lillian L.] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada. [Stewart, F. Marc] Seattle Canc Care Alliance, Seattle, WA USA. [Thompson, Michael] Aurora Hlth Care, Aurora Res Inst, Milwaukee, WI USA. [Vose, Julie M.] Univ Nebraska, Ctr Med, Omaha, NE 68198 USA. [Wiernik, Peter H.] Canc Res Fdn, Bronx, NY USA. RP Kantarjian, H (reprint author), Univ Texas Houston, MD Anderson Canc Ctr, 1400 Holcombe Blvd, Houston, TX 77030 USA. EM hkantarjian@mdanderson.org RI Bast, Robert/E-6585-2011; OI Bast, Robert/0000-0003-4621-8462; Cohn, Susan/0000-0001-5749-7650; Larson, Richard/0000-0001-9168-3203; Bhojwani, Deepa/0000-0002-7559-7927; Esteva, Francisco/0000-0003-2437-3920 FU NCI NIH HHS [P30 CA008748, P30 CA016672] NR 13 TC 42 Z9 43 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD AUG PY 2015 VL 90 IS 8 BP 996 EP 1000 DI 10.1016/j.mayocp.2015.06.001 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA CO4NQ UT WOS:000359138000005 PM 26211600 ER PT J AU Steensma, DP Shampo, MA Kyle, RA AF Steensma, David P. Shampo, Marc A. Kyle, Robert A. TI Max Perutz and the Structure of Hemoglobin SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material C1 [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Shampo, Marc A.; Kyle, Robert A.] Mayo Clin, Rochester, MN USA. RP Steensma, DP (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 4 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD AUG PY 2015 VL 90 IS 8 BP E89 EP E89 DI 10.1016/j.mayocp.2015.04.026 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CO4NQ UT WOS:000359138000002 PM 26250737 ER PT J AU Park, YK Sharp, GC Phillips, J Winey, BA AF Park, Yang-Kyun Sharp, Gregory C. Phillips, Justin Winey, Brian A. TI Proton dose calculation on scatter-corrected CBCT image: Feasibility study for adaptive proton therapy SO MEDICAL PHYSICS LA English DT Article DE proton therapy; adaptive; cone beam; scatter correction ID CONE-BEAM CT; RADIATION-THERAPY; CORRECTION ALGORITHM; HOUNSFIELD UNITS; REGISTRATION; RADIOTHERAPY; UNCERTAINTIES; CANCER; RECALCULATION; DISTRIBUTIONS AB Purpose: To demonstrate the feasibility of proton dose calculation on scatter-corrected cone-beam computed tomographic (CBCT) images for the purpose of adaptive proton therapy. Methods: CBCT projection images were acquired from anthropomorphic phantoms and a prostate patient using an on-board imaging system of an Elekta infinity linear accelerator. Two previously introduced techniques were used to correct the scattered x-rays in the raw projection images: uniform scatter correction (CBCTus) and a priori CT-based scatter correction (CBCTap). CBCT images were reconstructed using a standard FDK algorithm and GPU-based reconstruction toolkit. Soft tissue ROI-based HU shifting was used to improve HU accuracy of the uncorrected CBCT images and CBCTus, while no HU change was applied to the CBCTap. The degree of equivalence of the corrected CBCT images with respect to the reference CT image (CTref) was evaluated by using angular profiles of water equivalent path length (WEPL) and passively scattered proton treatment plans. The CBCTap was further evaluated in more realistic scenarios such as rectal filling and weight loss to assess the effect of mismatched prior information on the corrected images. Results: The uncorrected CBCT and CBCTus images demonstrated substantial WEPL discrepancies (7.3 +/- 5.3 mm and 11.1 +/- 6.6 mm, respectively) with respect to the CTref, while the CBCTap images showed substantially reduced WEPL errors (2.4 +/- 2.0 mm). Similarly, the CBCTap-based treatment plans demonstrated a high pass rate (96.0%+/- 2.5% in 2 mm/2% criteria) in a 3D gamma analysis. Conclusions: A priori CT-based scatter correction technique was shown to be promising for adaptive proton therapy, as it achieved equivalent proton dose distributions and water equivalent path lengths compared to those of a reference CT in a selection of anthropomorphic phantoms. (C) 2015 American Association of Physicists in Medicine. C1 [Park, Yang-Kyun] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Park, YK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM ykpark@mgh.harvard.edu FU Elekta; NCI Federal Share of program by Massachusetts General Hospital [C06 CA059267]; Proton Therapy Research and Treatment Center; IBA; National Science Foundation; National Institutes of Health FX Brian Winey has received grant support from Elekta and from the NCI Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center. Brian Winey has received travel funds from IBA and Elekta. Greg Sharp has received grant support from Elekta, the National Science Foundation, and the National Institutes of Health. NR 36 TC 5 Z9 5 U1 0 U2 7 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 J9 MED PHYS JI Med. Phys. PD AUG PY 2015 VL 42 IS 8 BP 4449 EP 4459 DI 10.1118/1.4923179 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CO1RN UT WOS:000358933000005 PM 26233175 ER PT J AU Wittrup, A Ai, A Liu, X Hamar, P Trifonova, R Charisse, K Manoharan, M Kirchhausen, T Lieberman, J AF Wittrup, Anders Ai, Angela Liu, Xing Hamar, Peter Trifonova, Radiana Charisse, Klaus Manoharan, Muthiah Kirchhausen, Tomas Lieberman, Judy TI Visualizing lipid-formulated siRNA release from endosomes and target gene knockdown SO NATURE BIOTECHNOLOGY LA English DT Article ID INTRACELLULAR TRAFFICKING; RNAI THERAPEUTICS; DELIVERY; NANOPARTICLES; AUTOPHAGY; PROTEIN; CELLS; GLYCOSPHINGOLIPIDS; MATURATION; REPORTER AB A central hurdle in developing small interfering RNAs (siRNAs) as therapeutics is the inefficiency of their delivery across the plasma and endosomal membranes to the cytosol, where they interact with the RNA interference machinery. With the aim of improving endosomal release, a poorly understood and inefficient process, we studied the uptake and cytosolic release of siRNAs, formulated in lipoplexes or lipid nanoparticles, by live-cell imaging and correlated it with knockdown of a target GFP reporter. siRNA release occurred invariably from maturing endosomes within similar to 5-15 min of endocytosis. Cytosolic galectins immediately recognized the damaged endosome and targeted it for autophagy. However, inhibiting autophagy did not enhance cytosolic siRNA release. Gene knockdown occurred within a few hours of release and required <2,000 copies of cytosolic siRNAs. The ability to detect cytosolic release of siRNAs and understand how it is regulated will facilitate the development of rational strategies for improving the cytosolic delivery of candidate drugs. C1 [Wittrup, Anders; Ai, Angela; Liu, Xing; Hamar, Peter; Trifonova, Radiana; Kirchhausen, Tomas; Lieberman, Judy] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02163 USA. [Wittrup, Anders] Lund Univ, Dept Clin Sci, Sect Oncol & Pathol, Lund, Sweden. [Hamar, Peter] Semmelweis Univ, Inst Pathophysiol, H-1085 Budapest, Hungary. [Charisse, Klaus; Manoharan, Muthiah] Alnylam Pharmaceut, Cambridge, MA USA. [Kirchhausen, Tomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Kirchhausen, Tomas; Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02163 USA. EM anders.wittrup@med.lu.se; judy.lieberman@childrens.harvard.edu FU US National Institutes of Health (NIH) [AI090671, CA139444]; Swedish Research Council; NIH [GM075252]; New England Regional Center of Excellence in Biodefense and Emerging Infectious Disease [AI057159] FX The authors thank E. Marino for maintaining the Imaging Resource used in this study and K. Ketman and N. Barteneva for technical assistance. This work was supported by US National Institutes of Health (NIH) grants AI090671 and CA139444 (J.L.), the Swedish Research Council (A.W.), NIH grant GM075252 (T.K.) and New England Regional Center of Excellence in Biodefense and Emerging Infectious Disease, Core Imaging Facility grant AI057159 (T.K.). NR 29 TC 39 Z9 39 U1 15 U2 72 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD AUG PY 2015 VL 33 IS 8 BP 870 EP + DI 10.1038/nbt.3298 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA CO6OB UT WOS:000359274900027 PM 26192320 ER PT J AU Alizadeh, AA Aranda, V Bardelli, A Blanpain, C Bock, C Borowski, C Caldas, C Califano, A Doherty, M Elsner, M Esteller, M Fitzgerald, R Korbel, JO Lichter, P Mason, CE Navin, N Pe'er, D Polyak, K Roberts, CWM Siu, L Snyder, A Stower, H Swanton, C Verhaak, RGW Zenklusen, JC Zuber, J Zucman-Rossi, J AF Alizadeh, Ash A. Aranda, Victoria Bardelli, Alberto Blanpain, Cedric Bock, Christoph Borowski, Christine Caldas, Carlos Califano, Andrea Doherty, Michael Elsner, Markus Esteller, Manel Fitzgerald, Rebecca Korbel, Jan O. Lichter, Peter Mason, Christopher E. Navin, Nicholas Pe'er, Dana Polyak, Kornelia Roberts, Charles W. M. Siu, Lillian Snyder, Alexandra Stower, Hannah Swanton, Charles Verhaak, Roel G. W. Zenklusen, Jean C. Zuber, Johannes Zucman-Rossi, Jessica TI Toward understanding and exploiting tumor heterogeneity SO NATURE MEDICINE LA English DT Article ID INTRATUMOR HETEROGENEITY; BREAST-CANCER; SINGLE CELLS; IN-SITU; RNA; RESISTANCE; EVOLUTION; CHALLENGE; PATIENT; TISSUES AB The extent of tumor heterogeneity is an emerging theme that researchers are only beginning to understand. How genetic and epigenetic heterogeneity affects tumor evolution and clinical progression is unknown. The precise nature of the environmental factors that influence this heterogeneity is also yet to be characterized. Nature Medicine, Nature Biotechnology and the Volkswagen Foundation organized a meeting focused on identifying the obstacles that need to be overcome to advance translational research in and tumor heterogeneity. Once these key questions were established, the attendees devised potential solutions. Their ideas are presented here. C1 [Alizadeh, Ash A.] Stanford Univ, Div Oncol, Dept Med, Sch Med, Stanford, CA 94305 USA. [Alizadeh, Ash A.] Stanford Univ, Div Hematol, Dept Med, Sch Med, Stanford, CA 94305 USA. [Alizadeh, Ash A.] Stanford Univ, Inst Canc, Dept Med, Sch Med, Stanford, CA 94305 USA. [Aranda, Victoria; Borowski, Christine] Nat Med, New York, NY 10021 USA. [Bardelli, Alberto] Univ Turin, Dept Oncol, Turin, Italy. [Bardelli, Alberto] IRCCS, Candiolo Canc Inst, FPO, Turin, Italy. [Blanpain, Cedric] ULB, Brussels, Belgium. [Bock, Christoph] Austrian Acad Sci, CeMM Res Ctr Mol Med, A-1010 Vienna, Austria. [Bock, Christoph] Med Univ Vienna, Dept Lab Med, Vienna, Austria. [Caldas, Carlos] Univ Cambridge, Dept Oncol, Cambridge, England. [Califano, Andrea; Pe'er, Dana] Columbia Univ, Dept Syst Biol, New York, NY USA. [Califano, Andrea] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY USA. [Califano, Andrea] Columbia Univ, Dept Biomed Informat, New York, NY USA. [Doherty, Michael] Genentech Inc, San Francisco, CA USA. [Elsner, Markus] Nat Biotechnol, New York, NY USA. [Esteller, Manel] Bellvitge Biomed Res Inst, Canc Epigenet & Biol Program, Barcelona, Catalonia, Spain. [Fitzgerald, Rebecca] Univ Cambridge, Hutchison MRC Res Ctr, MRC Canc Unit, Cambridge, England. [Korbel, Jan O.] European Mol Biol Lab, Genome Biol Unit, D-69012 Heidelberg, Germany. [Lichter, Peter] DKFZ, German Canc Res Ctr, Heidelberg, Germany. [Mason, Christopher E.] Weill Cornell Med Coll, New York, NY USA. [Navin, Nicholas] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA. [Navin, Nicholas; Verhaak, Roel G. W.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA. [Pe'er, Dana] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA. [Polyak, Kornelia] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Roberts, Charles W. M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Siu, Lillian] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Snyder, Alexandra] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Swanton, Charles] UCL, Inst Canc, London, England. [Swanton, Charles] Univ Coll London Hosp NHS Fdn Trust, London, England. [Swanton, Charles] Francis Crick Inst, London, England. [Verhaak, Roel G. W.] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA. [Zenklusen, Jean C.] NCI, Canc Genome Atlas Ctr Canc Gen, Bethesda, MD 20892 USA. [Zuber, Johannes] Vienna Bioctr VBC, Res Inst Mol Pathol IMP, Vienna, Austria. [Zucman-Rossi, Jessica] IUH, Inserm, UMR Genom Fonct Tumeurs Solides 1162, Paris, France. RP Stower, H (reprint author), Nat Med, New York, NY 10021 USA. EM h.stower@us.nature.com RI Bock, Christoph/B-6723-2008; OI Bock, Christoph/0000-0001-6091-3088; Snyder Charen, Alexandra/0000-0002-2606-3523; zucman-rossi, Jessica/0000-0002-5687-0334; Caldas, Carlos/0000-0003-3547-1489; Esteller, Manel/0000-0003-4490-6093; Alizadeh, Arash Ash/0000-0002-5153-5625 FU NCI NIH HHS [R01 CA169244] NR 36 TC 61 Z9 63 U1 7 U2 49 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 2015 VL 21 IS 8 BP 846 EP 853 DI 10.1038/nm.3915 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA CO5DY UT WOS:000359181000009 PM 26248267 ER PT J AU Hong, SY Moreno-Navarrete, JM Wei, XJ Kikukawa, Y Tzameli, I Prasad, D Lee, Y Asara, JM Fernandez-Real, JM Maratos-Flier, E Pissios, P AF Hong, Shangyu Moreno-Navarrete, Jose M. Wei, Xiaojing Kikukawa, Yusuke Tzameli, Iphigenia Prasad, Deepthi Lee, Yoonjin Asara, John M. Fernandez-Real, Jose Manuel Maratos-Flier, Eleftheria Pissios, Pavlos TI Nicotinamide N-methyltransferase regulates hepatic nutrient metabolism through Sirt1 protein stabilization SO NATURE MEDICINE LA English DT Article ID DIET-INDUCED OBESITY; LIPID-METABOLISM; HIGH-FAT; 1-METHYLNICOTINAMIDE MNA; CALORIE RESTRICTION; GENE-EXPRESSION; TRANSGENIC MICE; ADIPOSE-TISSUE; DIABETIC-RATS; NAD(+) AB Nicotinamide N-methyltransferase (Nnmt) methylates nicotinamide, a form of vitamin 83, to produce N-1-methylnicotinamide (MNAM). Nnmt has emerged as a metabolic regulator in adipocytes, but its role in the liver, the tissue with the strongest Nnmt expression, is not known. In spite of its overall high expression, here we find that hepatic expression of Nnmt is highly variable and correlates with multiple metabolic parameters in mice and humans. Further, we find that suppression of hepatic Nnmt expression in vivo alters glucose and cholesterol metabolism and that the metabolic effects of Nnmt in the liver are mediated by its product MNAM. Supplementation of high-fat diet with MNAM decreases serum and liver cholesterol and liver triglycerides levels in mice. Mechanistically, increasing Nnmt expression or MNAM levels stabilizes sirtuin 1 protein, an effect that is required for their metabolic benefits. In summary, we describe here a novel regulatory pathway for vitamin B3 that could provide a new opportunity for metabolic disease therapy. C1 [Hong, Shangyu; Wei, Xiaojing; Tzameli, Iphigenia; Prasad, Deepthi; Maratos-Flier, Eleftheria; Pissios, Pavlos] Beth Israel Deaconess Med Ctr, Div Diabet Endocrinol & Metab, Boston, MA 02215 USA. [Moreno-Navarrete, Jose M.; Fernandez-Real, Jose Manuel] Inst Invest Biomed Girona, Dept Diabet Endocrinol & Nutr, Girona, Spain. [Moreno-Navarrete, Jose M.; Fernandez-Real, Jose Manuel] CIBERobn, Madrid, Spain. [Kikukawa, Yusuke] Takeda Pharmaceut Ltd, Osaka, Japan. [Lee, Yoonjin] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Asara, John M.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. RP Pissios, P (reprint author), Beth Israel Deaconess Med Ctr, Div Diabet Endocrinol & Metab, Boston, MA 02215 USA. EM ppissios@bidmc.harvard.edu RI Moreno-Navarrete, Jose Maria/H-9772-2015; OI Kikukawa, Yusuke/0000-0002-5603-3181; Fernandez-Real, Jose Manuel/0000-0002-7442-9323 FU Takeda; US National Institute of Health [DK028082, DK083694]; Boston Area Diabetes Endocrinology Research Center (BADERC) [DK057521]; Instituto de Salud Carlos III [FIS-PI11/00214, FIS-PI12/02631]; Fondo Europeo de Desarrollo Regional (FEDER), Spain FX We would like to thank F.F. Liu, D. Adams, A.M. Real and M.J. Lee for technical assistance and J.S. Flier for advice. We thank S.M. Spiegelman and P. Puigserver (Dana-Farber Cancer Center, Boston, MA) for the donation of the Sirt1 and FoxO1 adenoviruses, D.E. Cohen (Brigham and Women's Hospital, Boston, MA) for lipoprotein analysis and R. Ortiz (University Hospital of Girona, Spain) for the pathology evaluation of the human liver biopsies. This work was supported by grants from Takeda, the US National Institute of Health DK028082 (E.M.F.), DK083694 (P.P.), Boston Area Diabetes Endocrinology Research Center (BADERC) grant DK057521 (P.P.), and by grants FIS-PI11/00214 and FIS-PI12/02631 to J.M.F.R. from the Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional (FEDER), Spain. NR 53 TC 15 Z9 15 U1 6 U2 21 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 2015 VL 21 IS 8 BP 887 EP 894 DI 10.1038/nm.3882 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA CO5DY UT WOS:000359181000015 PM 26168293 ER PT J AU Mahoney, KM Rennert, PD Freeman, GJ AF Mahoney, Kathleen M. Rennert, Paul D. Freeman, Gordon J. TI Combination cancer immunotherapy and new immunomodulatory targets SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID RENAL-CELL CARCINOMA; REGULATORY T-CELLS; ACTIVATED KILLER-CELLS; NON-HODGKIN-LYMPHOMA; COSTIMULATORY MOLECULE B7-H3; IMMUNE CHECKPOINT BLOCKADE; CHRONIC VIRAL-INFECTION; HUMAN PANCREATIC-CANCER; PREDICTS POOR SURVIVAL; HUMAN OVARIAN-CANCER AB Targeting immune checkpoints such as programmed cell death protein 1 (PD1), programmed cell death 1 ligand 1 (PDL1) and cytotoxic T lymphocyte antigen 4 (CTLA4) has achieved noteworthy benefit in multiple cancers by blocking immunoinhibitory signals and enabling patients to produce an effective antitumour response. Inhibitors of CTLA4, PD1 or PDL1 administered as single agents have resulted in durable tumour regression in some patients, and combinations of PD1 and CTLA4 inhibitors may enhance antitumour benefit. Numerous additional immunomodulatory pathways as well as inhibitory factors expressed or secreted by myeloid and stromal cells in the tumour microenvironment are potential targets for synergizing with immune checkpoint blockade. Given the breadth of potential targets in the immune system, critical questions to address include which combinations should move forward in development and which patients will benefit from these treatments. This Review discusses the leading drug targets that are expressed on tumour cells and in the tumour microenvironment that allow enhancement of the antitumour immune response. C1 [Mahoney, Kathleen M.; Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Mahoney, Kathleen M.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Haematol & Oncol, Boston, MA 02215 USA. [Rennert, Paul D.] SugarCone Biotech, Holliston, MA 01746 USA. [Rennert, Paul D.] Videre Biotherapeut, Watertown, MA 02472 USA. RP Freeman, GJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM gordon_freeman@dfci.harvard.edu FU Claudia Adams Barr Program for Innovative Cancer Research; American Association for Cancer Research [14-40-01-MAHO]; American Society of Clinical Oncology; Kidney Cancer Association; [P50CA101942]; [U54CA163125]; [P01AI054456]; [R01AI089955] FX G.J.F. acknowledges research support from grants P50CA101942, U54CA163125, P01AI054456 and R01AI089955. K.M.M. acknowledges research support from the Claudia Adams Barr Program for Innovative Cancer Research, an American Association for Cancer Research Basic Cancer Research Fellowship (14-40-01-MAHO), and an American Society of Clinical Oncology Young Investigator Award supported by the Kidney Cancer Association. NR 267 TC 125 Z9 127 U1 52 U2 157 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 EI 1474-1784 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD AUG PY 2015 VL 14 IS 8 BP 561 EP 584 DI 10.1038/nrd4591 PG 24 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA CO3BX UT WOS:000359032700018 PM 26228759 ER PT J AU Labus, JS Van Horn, JD Gupta, A Alayerdyan, M Torgerson, C Ashe-McNalley, C Irimia, A Hong, JY Naliboff, B Tillisch, K Mayer, EA AF Labus, Jennifer S. Van Horn, John D. Gupta, Arpana Alayerdyan, Mher Torgerson, Carinna Ashe-McNalley, Cody Irimia, Andrei Hong, Jui-Yang Naliboff, Bruce Tillisch, Kirsten Mayer, Emeran A. TI Multivariate morphological brain signatures predict patients with chronic abdominal pain from healthy control subjects SO PAIN LA English DT Article DE Structural magnetic resonance imaging; Brain; Females; Abdominal pain; Classification ID IRRITABLE-BOWEL-SYNDROME; PARTIAL LEAST-SQUARES; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; CYSTITIS/PAINFUL BLADDER SYNDROME; SURFACE-BASED ANALYSIS; GRAY-MATTER; SOMATOSENSORY CORTEX; VARIABLE SELECTION; AUDITORY-STIMULI; HUMAN AWARENESS AB Irritable bowel syndrome (IBS) is the most common chronic visceral pain disorder. The pathophysiology of IBS is incompletely understood; however, evidence strongly suggests dysregulation of the brain-gut axis. The aim of this study was to apply multivariate pattern analysis to identify an IBS-related morphometric brain signature that could serve as a central biological marker and provide new mechanistic insights into the pathophysiology of IBS. Parcellation of 165 cortical and subcortical regions was performed using FreeSurfer and the Destrieux and Harvard-Oxford atlases. Volume, mean curvature, surface area, and cortical thickness were calculated for each region. Sparse partial least squares discriminant analysis was applied to develop a diagnostic model using a training set of 160 females (80 healthy controls and 80 patients with IBS). Predictive accuracy was assessed in an age-matched holdout test set of 52 females (26 healthy controls and 26 patients with IBS). A 2-component classification algorithm comprising the morphometry of (1) primary somatosensory and motor regions and (2) multimodal network regions explained 36% of the variance. Overall predictive accuracy of the classification algorithm was 70%. Small effect size associations were observed between the somatosensory and motor signature and nongastrointestinal somatic symptoms. The findings demonstrate that the predictive accuracy of a classification algorithm based solely on regional brain morphometry is not sufficient, but they do provide support for the utility of multivariate pattern analysis for identifying meaningful neurobiological markers in IBS. C1 [Labus, Jennifer S.; Gupta, Arpana; Alayerdyan, Mher; Ashe-McNalley, Cody; Hong, Jui-Yang; Naliboff, Bruce; Tillisch, Kirsten; Mayer, Emeran A.] Univ Calif Los Angeles, Oppenheimer Family Ctr Neurobiol Stress, Los Angeles, CA 90095 USA. [Labus, Jennifer S.; Gupta, Arpana; Alayerdyan, Mher; Ashe-McNalley, Cody; Hong, Jui-Yang; Naliboff, Bruce; Tillisch, Kirsten; Mayer, Emeran A.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. [Labus, Jennifer S.; Gupta, Arpana; Naliboff, Bruce; Tillisch, Kirsten; Mayer, Emeran A.] Univ Calif Los Angeles, Div Digest Dis, Los Angeles, CA 90095 USA. [Labus, Jennifer S.; Naliboff, Bruce; Tillisch, Kirsten; Mayer, Emeran A.] Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90095 USA. [Labus, Jennifer S.; Naliboff, Bruce; Tillisch, Kirsten; Mayer, Emeran A.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90095 USA. [Labus, Jennifer S.; Naliboff, Bruce; Tillisch, Kirsten; Mayer, Emeran A.] Pain & Interocept Network PAIN, Los Angeles, CA USA. [Van Horn, John D.; Torgerson, Carinna; Irimia, Andrei] Univ So Calif, Keck Sch Med, INI, Los Angeles, CA 90033 USA. [Van Horn, John D.; Torgerson, Carinna; Irimia, Andrei] Univ So Calif, Keck Sch Med, Lab Neuro Imaging LONI, Los Angeles, CA 90033 USA. [Hong, Jui-Yang] Univ Calif Los Angeles, Dept Biomed Engn, Los Angeles, CA 90095 USA. [Tillisch, Kirsten] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Labus, JS (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Oppenheimer Family Ctr Neurobiol Stress, CHS 42-210 MC737818,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM jlabus@ucla.edu FU National Institutes of Health [R01 DK048351, P50DK64539, R01 AT007137, K23 DK073451, K08 DK071626, R03 DK084169] FX This research was supported in part by grants from the National Institutes of Health: R01 DK048351 (E.A.M.), P50DK64539 (E.A.M.), R01 AT007137 (K.T.), K23 DK073451 (K.T.), K08 DK071626 (J.S.L.), and R03 DK084169 (J.S.L.). Pilot scans were provided by the Ahmanson-Lovelace Brain Mapping Center, UCLA. NR 67 TC 8 Z9 9 U1 3 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD AUG PY 2015 VL 156 IS 8 BP 1545 EP 1554 DI 10.1097/j.pain.0000000000000196 PG 10 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA CO0BQ UT WOS:000358815500022 PM 25906347 ER PT J AU Betancourt, TS Gilman, SE Brennan, RT Zahn, I VanderWeele, TJ AF Betancourt, Theresa S. Gilman, Stephen E. Brennan, Robert T. Zahn, Ista VanderWeele, Tyler J. TI Identifying Priorities for Mental Health Interventions in War-Affected Youth: A Longitudinal Study SO PEDIATRICS LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; FORMER CHILD SOLDIERS; POSTTRAUMATIC-STRESS-DISORDER; BOSNIAN ADOLESCENTS; EXPOSURE; CONFLICT; VIOLENCE; RISK; EXPERIENCES; ADJUSTMENT AB BACKGROUND: War-affected youth often suffer from multiple co-occurring mental health problems. These youth often live in low-resource settings where it may be infeasible to provide mental health services that simultaneously address all of these co-occurring mental health issues. It is therefore important to identify the areas where targeted interventions would do the most good. METHODS: This analysis uses observational data from 3 waves of a longitudinal study on mental health in asampleof529war-affectedyouth(24.2% female; ages 10-17 at T1,2002) in SierraLeone. We regressed 4 mental health outcomes at T3 (2008) on internalizing (depression/anxiety) and externalizing (hostility/aggression) problems and prosocial attitudes/behaviors and community variables at T2 (2004) controlling for demographics, war exposures, and previous mental health scores at T1, allowing us to assess the relative impact of potential mental health intervention targets in shaping mental health outcomes over time. RESULTS: Controlling for baseline covariates at T1 and all other exposures/potential intervention targets at T2, we observed a significant association between internalizing problems at T2 and 3 of the 4 outcomes at T3: internalizing (beta = 0.27, 95% confidence interval [CI]: 0.11-0.42), prosocial attitudes (beta = -0.20, 95% CI: -0.33 to -0.07) and posttraumatic stress symptoms (beta = 0.22, 95% CI: 0.02-0.43). No other potential intervention target had similar substantial effects. CONCLUSIONS: Reductions in internalizing may have multiple benefits for other mental health outcomes at a later point in time, even after controlling for confounding variables. C1 [Betancourt, Theresa S.; Brennan, Robert T.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. [Gilman, Stephen E.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Gilman, Stephen E.; VanderWeele, Tyler J.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Gilman, Stephen E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Zahn, Ista] Harvard Univ, FXB Ctr Hlth & Human Rights, Cambridge, MA 02138 USA. [Zahn, Ista] Harvard Univ, Inst Quantitat Social Sci, Cambridge, MA 02138 USA. RP Betancourt, TS (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Global Hlth & Populat, 665 Huntington Ave,12th Floor, Boston, MA 02115 USA. EM theresa_betancourt@harvard.edu RI Gilman, Stephen/E-7632-2010 OI Gilman, Stephen/0000-0002-8331-6419 FU US Institute of Peace; USAID/Displaced Children and Orphans Fund; National Institute of Mental Health [R01HD073349-01, R01ES017876, 1K01MH077246-01A2]; International Rescue Committee; Francois-Xavier Bagnoud Center for Health and Human Rights FX Supported by the US Institute of Peace, USAID/Displaced Children and Orphans Fund, grants R01HD073349-01, R01ES017876, and 1K01MH077246-01A2 from the National Institute of Mental Health, the International Rescue Committee, and the Francois-Xavier Bagnoud Center for Health and Human Rights. NR 30 TC 2 Z9 2 U1 0 U2 8 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD AUG PY 2015 VL 136 IS 2 BP E344 EP E350 DI 10.1542/peds.2014-1521 PG 7 WC Pediatrics SC Pediatrics GA CN9SA UT WOS:000358788100006 PM 26148954 ER PT J AU Ramsey, H Zhang, Q Wu, MX AF Ramsey, Haley Zhang, Qi Wu, Mel X. TI Mitoquinone restores platelet production in irradiation-induced thrombocytopenia SO PLATELETS LA English DT Article DE Megakaryocytes; Mitoquinone; Reactive Oxygen Species; Thrombocytopenia ID HEMATOPOIETIC STEM-CELLS; OXIDATIVE DNA-DAMAGE; SMOOTH-MUSCLE-CELLS; ERROR-PRONE REPAIR; MYELODYSPLASTIC SYNDROMES; GENOMIC INSTABILITY; GENE-EXPRESSION; IEX-1; STRESS; ACCUMULATION AB Myelodysplastic syndromes (MDS) are hallmarked by cytopenia and dysplasia of hematopoietic cells, often accompanied by mitochondrial dysfunction and increases of reactive oxygen species (ROS) within affected cells. However, it is not known whether the increase in ROS production is an instigator or a byproduct of the disease. The present investigation shows that mice lacking immediate early responsive gene X-1 (IEX-1) exhibit lineage specific increases in ROS production and abnormal cytology upon radiation in blood cell types commonly identified in MDS. These affected cell lineages chiefly have the bone marrow as a primary site of differentiation and maturation, while cells with extramedullary differentiation and maturation like B- and T-cells remain unaffected. Increased ROS production is likely to contribute significantly to irradiation-induced thrombocytopenia in the absence of IEX-1 as demonstrated by effective reversal of the disorder after mitoquinone (MitoQ) treatment, a mitochondria-specific antioxidant. MitoQ reduced intracellular ROS production within megakaryocytes and platelets. It also normalized mitochondrial membrane potential and superoxide production in platelets in irradiated, IEX-1 deficient mice. The lineage-specific effects of mitochondria! ROS may help us understand the etiology of thrombocytopenia in association with MDS in a subgroup of the patients. C1 [Ramsey, Haley; Zhang, Qi; Wu, Mel X.] Harvard Univ, Sch Med, Dept Dermatol, Wellman Ctr Photomed,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Wu, MX (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Edwards 222,50 Blossom St, Boston, MA 02114 USA. EM mwu2@partners.org FU National Institutes of Health [CA158756, AI089779, DA028378] FX H.R. designed and performed the research, analyzed data, and wrote the manuscript. Q.Z performed research. M.W. has designed and supervised research and wrote the manuscript. This work is supported by the National Institutes of Health Grants CA158756, AI089779, and DA028378 to M.X.W. NR 45 TC 2 Z9 2 U1 0 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0953-7104 EI 1369-1635 J9 PLATELETS JI Platelets PD AUG PY 2015 VL 26 IS 5 BP 459 EP 466 DI 10.3109/09537104.2014.935315 PG 8 WC Cell Biology; Hematology SC Cell Biology; Hematology GA CO3CO UT WOS:000359034400017 PM 25025394 ER PT J AU Jakubowski, JA Zhou, CM Winters, KJ Lachno, DR Howard, J Payne, CD Mant, T Jurcevic, S Frelinger, AL AF Jakubowski, Joseph A. Zhou, Chunmei Winters, Kenneth J. Lachno, D. Richard Howard, Jo Payne, Christopher D. Mant, Timothy Jurcevic, Stipo Frelinger, Andrew L., III TI The effect of prasugrel on ADP-stimulated markers of platelet activation in patients with sickle cell disease SO PLATELETS LA English DT Article DE ADP; biomarkers; P2Y(12) receptor antagonist; platelets; prasugrel; sickle cell disease ID PROCOAGULANT ACTIVITY; INTEGRATED ANALYSIS; ACTIVE METABOLITE; ANEMIA; COAGULATION; HYPERCOAGULABILITY; ANTIPLATELET; CLOPIDOGREL; MONOCYTE AB Platelets of patients with sickle cell disease (SCD) show evidence of mild activation in the non-crisis steady state and greater activation during vaso-occlusive crises (VOC). Prasugrel, a potent inhibitor of ADP-mediated platelet activation and aggregation, may be useful in attenuating VOC. We compared platelet responses to ADP stimulation in patients with SCD and healthy subjects before and after treatment with prasugrel. In a phase 1 study, platelet biomarker levels were assessed in 12 adult patients with SCD and 13 healthy subjects before and after 12 +/- 2 days of 5.0 or 7.5 mg/day prasugrel. The following were determined in whole blood samples stimulated with 20 mu M ADP: (i) percentages of monocytes and neutrophils with adherent platelets (cell-platelet aggregates); (ii) the relative number (mass) of platelets associated with each monocyte and neutrophil as reported by CD61 mean fluorescence intensity (MFI) of the monocyte-platelet and neutrophil-platelet aggregates; (iii) the percentages of platelets positive for surface expression of CD40 ligand (CD4OL), P-selectin (CD62p) and activated glycoprotein lib-Illa (GPIlb-IIIa); and (iv) the percentages of platelets and monocyte-platelet aggregates positive for surface tissue factor (TF) expression. At baseline, there were no significant differences between cohorts in the percentages of platelets expressing activation biomarkers. Following 12 days of prasugrel administration, the percentages of platelets expressing activation biomarkers following ADP stimulation were reduced in both cohorts, and there were no significant differences between groups. Both patients with SCD and healthy subjects had significant reductions in the monocyte-platelet and neutrophil-platelet aggregate MFI and the percentage of platelets expressing P-selectin and activated GPIlb-IIIa (all p<0.05). Healthy subjects also had significant reductions in monocyte-platelet aggregate percentages (p=0.004), neutrophil-platelet aggregate percentages (p=0.011) and the percentage of CD40L-positive platelets (p=0.044) that were not observed in patients with SCD. Prasugrel administration to SCD patients attenuates ex vivo ADP-stimulated platelet activation as measured by the percentage of platelets positive for P-selectin and GPIlb-111a, thus reducing the proportion of platelets that may participate in aggregates. Furthermore, prasugrel decreases ex vivo ADP-stimulated platelet aggregation with monocytes and neutrophils as measured by the monocyte-platelet and neutrophil-platelet aggregate MFI. This implies that in the presence of prasugrel, fewer platelets adhere to monocytes and neutrophils, which may result in reducing cell-platelet aggregate size. Therefore, reduced platelet reactivity and decreased size of leukocyte-platelet aggregates suggest additional mechanisms by which prasugrel may provide benefit to patients with SCD and support further investigation of possible therapeutic benefits of prasugrel in this population. C1 [Jakubowski, Joseph A.; Zhou, Chunmei; Winters, Kenneth J.] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. [Lachno, D. Richard; Payne, Christopher D.] Eli Lilly & Co, Windlesham, Surrey, England. [Howard, Jo] Guys & St Thomas Hosp, London SE1 9RT, England. [Mant, Timothy] Guys Hosp, Quintiles Drug Res Unit, London SE1 9RT, England. [Jurcevic, Stipo] Kings Coll London, London WC2R 2LS, England. [Frelinger, Andrew L., III] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston Childrens Hosp,Div Hematol Oncol,Ctr Plate, Boston, MA 02115 USA. RP Jakubowski, JA (reprint author), Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. EM joseph@lilly.com FU MRC Centre for Transplantation; Eli Lilly; National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St. Thomas' NHS Foundation Trust and King's College London; Eli Lilly and Company; Daiichi Sankyo Company, Ltd.; GLSynthesis, Inc. FX In the previous 3 years, Drs. Joseph Jakubowski, Kenneth Winters, and D. Richard Lachno, as well as Ms. Zhou and Mr. Payne, are employees and minor stock holders in Eli Lilly and Company. Dr. Jurcevic is supported by the MRC Centre for Transplantation and received funding from Eli Lilly for consumables and work hours of laboratory staff. Dr. Mantis supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St. Thomas' NHS Foundation Trust and King's College London. Dr. Frelinger had grants from Eli Lilly and Company, Daiichi Sankyo Company, Ltd., and GLSynthesis, Inc. Dr. Howard has served as a speaker for Novartis and an advisory group participant for Novartis and Aes-Rx. NR 29 TC 2 Z9 2 U1 1 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0953-7104 EI 1369-1635 J9 PLATELETS JI Platelets PD AUG PY 2015 VL 26 IS 5 BP 474 EP 479 DI 10.3109/09537104.2014.940887 PG 6 WC Cell Biology; Hematology SC Cell Biology; Hematology GA CO3CO UT WOS:000359034400019 PM 25140584 ER PT J AU Canuti, M Buka, S Farsani, SMJ Munnink, BBO Jebbink, MF van Beveren, NJM de Haan, L Goldstein, J Seidman, LJ Tsuang, MT Storosum, JG van der Hoek, L AF Canuti, Marta Buka, Stephen Farsani, Seyed Mohammad Jazaeri Munnink, Bas B. Oude Jebbink, Maarten F. van Beveren, Nico J. M. de Haan, Lieuwe Goldstein, Jill Seidman, Larry J. Tsuang, Ming T. Storosum, Jitschak G. van der Hoek, Lia TI Reduced maternal levels of common viruses during pregnancy predict offspring psychosis: Potential role of enhanced maternal immune activity? SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Psychosis; Schizophrenia; Bipolar disorder; Viral hypothesis for schizophrenia; VIDISCA; Virus discovery; Anelloviruses ID CENTRAL-NERVOUS-SYSTEM; NEW-ENGLAND FAMILY; ADULT SCHIZOPHRENIA; AUTOIMMUNE-DISEASES; HUMAN ANELLOVIRUSES; BIPOLAR DISORDER; TT-VIRUS; RISK; INDIVIDUALS; INFECTIONS AB Viral infections during the prenatal or early childhood periods are one of the environmental factors which might play an etiological role in psychoses. Several studies report higher antibody levels against viruses during pregnancy in blood of mothers of offspring with psychotic disorders, but the presence of such viruses has never been demonstrated. The goal of this study was to investigate the potential association between viral infections during pregnancy and progeny with psychotic disorders and, for this purpose, we performed a nested case control study involving pregnant mothers of offspring with schizophrenia or bipolar disorder with psychotic features (cases, N = 43) and pregnant women with healthy offspring (controls, N = 95). Since several potential viral candidates have been suggested in prior work, a broad-spectrum virus detection system was necessary. A metagenomic analysis performed with the virus discovery method VIDISCA-454 revealed only common blood-associated viruses in all cohorts. However, a significantly lower viral prevalence was detected in the group of cases and in the sub-population of pregnant mothers of offspring with schizophrenia (p < 0.05). Consistent with the existing inverse correlation between the level of these viruses and the immunocompetence of an individual, we hypothesized the presence of a higher immune activity during pregnancy in mothers whose offspring later develop a psychotic disorder as compared to controls. Combining our results with previously available literature data on antibody levels during the gestation period suggests that a more prominent maternal immune activity can be considered a risk factor for developing psychosis. (C) 2015 Elsevier B.V. All rights reserved. C1 [Canuti, Marta; Farsani, Seyed Mohammad Jazaeri; Munnink, Bas B. Oude; Jebbink, Maarten F.; van der Hoek, Lia] Univ Amsterdam, Acad Med Ctr, Ctr Infect & Immun Amsterdam CINIMA, Lab Expt Virol,Dept Med Microbiol, NL-1105 AZ Amsterdam, Netherlands. [Buka, Stephen] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA. [van Beveren, Nico J. M.] Antes, Inst Mental Hlth Care, Rotterdam, Netherlands. [van Beveren, Nico J. M.] Erasmus Univ, Med Ctr, Dept Neurosci, Rotterdam, Netherlands. [de Haan, Lieuwe; Storosum, Jitschak G.] Univ Amsterdam, Acad Med Ctr, Dept Psychiat, NL-1105 AZ Amsterdam, Netherlands. [Goldstein, Jill] Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA. [Goldstein, Jill; Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Goldstein, Jill] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Seidman, Larry J.] Massachusetts Mental Hlth Ctr Publ Psychiat, Boston, MA USA. [Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genom, Inst Genom Med, La Jolla, CA 92093 USA. [Tsuang, Ming T.] Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. [Goldstein, Jill] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [van Beveren, Nico J. M.] Erasmus Univ, Med Ctr, Dept Psychiat, Rotterdam, Netherlands. RP Canuti, M (reprint author), Mem Univ Newfoundland, Dept Biol, 232 Elizabeth Ave, St John, NF A1B 3X9, Canada. EM marta.canuti@gmail.com; stephen_buka@brown.edu OI Canuti, Marta/0000-0002-9959-128X FU European Community [223498]; Stanley Medical Research Institute; NIMH [R01MH63951] FX This study was supported by funding from the European Community's Seventh Framework Programme (FP7/2007-2013) Under the project EMPERIE, EC grant agreement number 223498. Data collection for this study was supported by the National Institute of Mental Health (NIMH) RO1 MH56956 (J.M.G., P.I.). In addition, original sample ascertainment was in part also supported by grants from the Stanley Medical Research Institute (S.L.B., L.J.S. 1994-1997) and NIMH R01MH63951 (L.J.S., P.I.). NR 62 TC 1 Z9 1 U1 4 U2 6 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 2015 VL 166 IS 1-3 BP 248 EP 254 DI 10.1016/j.schres.2015.04.037 PG 7 WC Psychiatry SC Psychiatry GA CO5AO UT WOS:000359172200040 PM 26004694 ER PT J AU Rai, SK Burns, LC De Vera, MA Haji, A Giustini, D Choi, HK AF Rai, Sharan K. Burns, Lindsay C. De Vera, Mary A. Haji, Aliya Giustini, Dean Choi, Hyon K. TI The economic burden of gout: A systematic review SO SEMINARS IN ARTHRITIS AND RHEUMATISM LA English DT Review DE Gout; Economics; Cost-of-illness; Direct cost; Indirect cost; Health care costs ID HEALTH-CARE COSTS; ADMINISTRATIVE CLAIMS ANALYSIS; NUTRITION EXAMINATION SURVEY; US GENERAL-POPULATION; RHEUMATOID-ARTHRITIS; NATIONAL-HEALTH; SERUM URATE; PREVALENCE; MANAGEMENT; ATTACKS AB Objective: Gout is a painful and disabling joint disease that constitutes the most common inflammatory arthritis in the US. To clarify the economic impact of gout, we systematically reviewed the literature on the direct and indirect costs associated with this disease. Methods: We conducted a literature search of MEDLINE, EMBASE, International Pharmaceutical Abstracts, NHS Economic Evaluation, and CINAHL databases to identify studies of gout and economics. We systematically reviewed published studies that met our inclusion criteria and extracted and summarized all relevant economic parameters. Reported costs were inflation-adjusted to 2013 US dollars (USD). Results: A total of 15 studies met all eligibility criteria. Three controlled studies reported all-cause total direct costs based on specific populations (i.e., $4733, $16,925, and $18,362 per capita among employed, elderly, and treatment-refractory gout populations, respectively, and $2562, $10,590, and $7188 among corresponding non-gout patients). Two additional studies, although uncontrolled, allowed for estimation of total all-cause direct costs in unselected gout populations ($11,080 and $13,170). Gout-related costs ranged from $172 to $6179, depending on population characteristics. Six studies reported positive associations of direct costs with SUA level, gout attack frequency, or presence of tophi. Four studies reported on indirect costs, which were estimated to be as high as $4341 USD. Conclusion: The available data suggest that gout patients incur substantially greater direct and indirect costs as compared with gout-free individuals among elderly and treatment-refractory gouty patients, whereas the costs are considerably less among younger, employed gouty patients. Further, direct costs increased with worsening disease characteristics. (C) 2015 Elsevier Inc. All rights reserved. C1 [Rai, Sharan K.; Burns, Lindsay C.; De Vera, Mary A.; Choi, Hyon K.] Arthrit Res Canada, Vancouver, BC, Canada. [Rai, Sharan K.] Univ British Columbia, Dept Expt Med, Vancouver, BC V5Z 1M9, Canada. [Burns, Lindsay C.] York Univ, Dept Psychol, Toronto, ON M3J 2R7, Canada. [De Vera, Mary A.] Univ British Columbia, Fac Pharmaceut Sci, Vancouver, BC V5Z 1M9, Canada. [Haji, Aliya] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V5Z 1M9, Canada. [Giustini, Dean; Choi, Hyon K.] Univ British Columbia, Fac Med, Vancouver, BC, Canada. [Choi, Hyon K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. RP Choi, HK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. EM Choi.Hyon@mgh.harvard.edu RI Giustini, Dean/A-3714-2014 OI Giustini, Dean/0000-0002-6197-8788 NR 34 TC 7 Z9 7 U1 1 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0049-0172 EI 1532-866X J9 SEMIN ARTHRITIS RHEU JI Semin. Arthritis Rheum. PD AUG PY 2015 VL 45 IS 1 BP 75 EP 80 DI 10.1016/j.semarthrit.2015.02.004 PG 6 WC Rheumatology SC Rheumatology GA CO0EH UT WOS:000358822400012 PM 25912932 ER PT J AU Hoo, GWS AF Hoo, Guy W. Soo TI The Role of Noninvasive Ventilation in the Hospital and Outpatient Management of Chronic Obstructive Pulmonary Disease SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE COPD; noninvasive ventilation; hypercapnia; chronic respiratory failure ID POSITIVE-PRESSURE VENTILATION; ACUTE RESPIRATORY-FAILURE; RANDOMIZED CONTROLLED-TRIAL; COMMUNITY-ACQUIRED-PNEUMONIA; STABLE HYPERCAPNIC COPD; PROPORTIONAL ASSIST VENTILATION; NOCTURNAL NASAL VENTILATION; INTENSIVE-CARE UNITS; AIR-FLOW LIMITATION; TERM-FOLLOW-UP AB Positive pressure noninvasive ventilation (NIV) has become widely accepted in the treatment of both hospitalized and outpatient subjects with chronic obstructive pulmonary disease (COPD). The support has evolved over the past two decades to be part of first-line management in acute exacerbations of COPD and is also instrumental in discontinuing mechanical ventilation in COPD patients with acute respiratory failure. It is also suitable for treatment of COPD with other associated conditions including pneumonia, following lung resectional surgery, with concomitant obstructive sleep apnea and as part of end-of-life care. Short-term application can also facilitate some endoscopic procedures that may otherwise require endotracheal intubation. Outpatient use of NIV in COPD has garnered much attention, but the support has not been as robust as with NIV in hospitalized patients. However, an approach with higher pressures with a goal of significant reduction in daytime PaCO2 may be an effective strategy. NIV can also facilitate exercise training in pulmonary rehabilitation. A portable device which can augment tidal volume during ambulation and other activities of daily living may further expand the use of NIV in COPD patients. C1 [Hoo, Guy W. Soo] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Pulm & Crit Care Sect,West Los Angeles VA Healthc, Los Angeles, CA 90073 USA. RP Hoo, GWS (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Pulm & Crit Care Sect 111Q,West Los Angeles VA He, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Guy.SooHoo@va.gov NR 127 TC 1 Z9 1 U1 1 U2 6 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1069-3424 EI 1098-9048 J9 SEMIN RESP CRIT CARE JI Semin. Respir. Crit. Care Med. PD AUG PY 2015 VL 36 IS 4 BP 616 EP 629 DI 10.1055/s-0035-1556074 PG 14 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CO0CI UT WOS:000358817300014 PM 26238646 ER PT J AU Tsai, AC Burns, BFO AF Tsai, Alexander C. Burns, Bridget F. O. TI Syndemics of psychosocial problems and HIV risk: A systematic review of empirical tests of the disease interaction concept SO SOCIAL SCIENCE & MEDICINE LA English DT Review DE AIDS/HIV; Social determinants ID RANDOMIZED CONTROLLED-TRIAL; SEVERE MENTAL ILLNESSES; SUBSTANCE USE DISORDERS; SOUTH-AFRICAN TOWNSHIP; UNSTABLY HOUSED WOMEN; DUAL DIAGNOSIS; BISEXUAL MEN; STATISTICAL INTERACTIONS; BIOLOGICAL INTERACTION; PSYCHIATRIC-DISORDERS AB In the theory of syndemics, diseases co-occur in particular temporal or geographical contexts due to harmful social conditions (disease concentration) and interact at the level of populations and individuals, with mutually enhancing deleterious consequences for health (disease interaction). This theory has widespread adherents in the field, but the extent to which there is empirical support for the concept of disease interaction remains unclear. In January 2015 we systematically searched 7 bibliographic databases and tracked citations to highly cited publications associated with the theory of syndemics. Of the 783 records, we ultimately included 34 published journal articles, 5 dissertations, and 1 conference abstract. Most studies were based on a cross-sectional design (32 [80%]), were conducted in the U.S. (32 [80%]), and focused on men who have sex with men (21 [53%]). The most frequently studied psychosocial problems were related to mental health (33 [83%]), substance abuse (36 [90%]), and violence (27 [68%]); while the most frequently studied outcome variables were HIV transmission risk behaviors (29 [73%]) or HIV infection (9 [23%]). To test the disease interaction concept, 11 (28%) studies used some variation of a product term, with less than half of these (5/11 [45%]) providing sufficient information to interpret interaction both on an additive and on a multiplicative scale. The most frequently used specification (31 [78%]) to test the disease interaction concept was the sum score corresponding to the total count of psychosocial problems. Although the count variable approach does not test hypotheses about interactions between psychosocial problems, these studies were much more likely than others (14/31 [45%] vs. 0/9 [0%]; chi(2) = 6.25, P = 0.01) to incorporate language about "synergy" or "interaction" that was inconsistent with the statistical models used. Therefore, more evidence is needed to assess the extent to which diseases interact, either at the level of populations or individuals, to amplify HIV risk. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Tsai, Alexander C.; Burns, Bridget F. O.] 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. RP Tsai, AC (reprint author), MGH Global Hlth, Suite 722,125 Nashua St, Boston, MA 02114 USA. EM actsai@partners.org OI Tsai, Alexander/0000-0001-6397-7917 FU Harvard University Center for AIDS Research (U.S. National Institutes of Health [NIH]) [P30AI060354]; NIH [K23MH096620]; Robert Wood Johnson Health and Society Scholars Program FX We thank the following individuals for responding to our queries for additional information about their work: Sonya Arreola, Helen Bates, Star Chen, Typhanye Dyer,Mackey Friedman, Abbey Hatcher, Seth Kalichman, Glenn-Milo Santos, and Soraya Seedat. We also thank Ingrid Katz, Mark Siedner, Sheri Weiser, and participants at the weekly work-in-progress seminar sponsored by the Harvard University Center for AIDS Research (U.S. National Institutes of Health [NIH] P30AI060354) for their thoughtful and constructive comments on earlier drafts of this manuscript. Our acknowledgment of their assistance should not be construed as suggesting their endorsement of any manuscript contents or conclusions. No specific funding was received for the conduct of this study, but salary support was provided through NIH K23MH096620 and the Robert Wood Johnson Health and Society Scholars Program. NR 103 TC 13 Z9 13 U1 5 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD AUG PY 2015 VL 139 BP 26 EP 35 DI 10.1016/j.socscimed.2015.06.024 PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA CO4ZC UT WOS:000359168400004 PM 26150065 ER PT J AU Bhatt, AB Buck, JS Zuflacht, JP Milian, J Kadivar, S Gauvreau, K Singh, MN Creager, MA AF Bhatt, Ami B. Buck, J. Stewart Zuflacht, Jonah P. Milian, Jessica Kadivar, Samoneh Gauvreau, Kimberlee Singh, Michael N. Creager, Mark A. TI Distinct effects of losartan and atenolol on vascular stiffness in Marfan syndrome SO VASCULAR MEDICINE LA English DT Article DE angiotensin receptor blocker; aortic stiffness; augmentation index; beta-receptor blocker; Marfan syndrome; pulse wave velocity ID PULSE-WAVE VELOCITY; AORTIC-ROOT DILATION; 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM GUIDELINES; CONVERTING-ENZYME-INHIBITION; BETA-ADRENERGIC-BLOCKADE; ARTERIAL STIFFNESS; BLOOD-PRESSURE; ESSENTIAL-HYPERTENSION; DIASTOLIC DYSFUNCTION; AUGMENTATION INDEX AB We conducted a randomized, double-blind trial of losartan (100 mg QD) versus atenolol (50 mg QD) for 6 months in adults with Marfan syndrome. Carotid-femoral pulse wave velocity (PWV), central augmentation index (AIx), aortic diameter and left ventricular (LV) function were assessed with arterial tonometry and echocardiography. Thirty-four subjects (18 female; median age 35 years, IQR 27, 45) were randomized. Central systolic and diastolic blood pressure decreased comparably with atenolol and losartan (p = 0.64 and 0.31, respectively); heart rate decreased with atenolol (p = 0.02), but not with losartan. PWV decreased in patients treated with atenolol (-1.15 +/- 1.68 m/s; p = 0.01), but not in those treated with losartan (-0.22 +/- 0.59 m/s; p = 0.15; between-group difference p = 0.04). In contrast, AIx decreased in the losartan group (-9.6 +/- 8.6%; p < 0.001) but not in the atenolol group (0.9 +/- 6.2%, p = 0.57; between-group difference p < 0.001). There was no significant change in aortic diameters or LV ejection fraction in either treatment group. In adults with Marfan syndrome, 6 months of treatment with atenolol improves PWV, whereas losartan reduces the AIx. By improving vascular stiffness via distinct mechanisms of action, there is physiologic value to considering the use of both medications in individuals with Marfan syndrome. C1 [Bhatt, Ami B.; Buck, J. Stewart; Zuflacht, Jonah P.; Milian, Jessica; Kadivar, Samoneh; Singh, Michael N.; Creager, Mark A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bhatt, Ami B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bhatt, Ami B.; Gauvreau, Kimberlee; Singh, Michael N.] Childrens Hosp Boston, Boston, MA USA. [Bhatt, Ami B.; Gauvreau, Kimberlee; Singh, Michael N.; Creager, Mark A.] Harvard Univ, Sch Med, Boston, MA USA. RP Bhatt, AB (reprint author), Massachusetts Gen Hosp, Yawkey 5B,55 Fruit St, Boston, MA 02114 USA. EM abhatt@mgh.harvard.edu FU National Marfan Foundation, Port Washington, NY; American College of Cardiology Merck Fellowship in Cardiovascular and Metabolic Disease, Washington, DC, USA FX This work was supported by the National Marfan Foundation, Port Washington, NY and the American College of Cardiology Merck Fellowship in Cardiovascular and Metabolic Disease, Washington, DC, USA. NR 60 TC 7 Z9 7 U1 0 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1358-863X EI 1477-0377 J9 VASC MED JI Vasc. Med. PD AUG PY 2015 VL 20 IS 4 BP 317 EP 325 DI 10.1177/1358863X15569868 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CO8JI UT WOS:000359414300002 PM 25795452 ER PT J AU Clark, SL Aberg, KA Nerella, S Kumar, G McClay, JL Chen, WN Xie, LYY Harada, A Shabalin, AA Gao, GM Bergen, SE Hultman, CM Magnusson, PKE Sullivan, PF van den Oord, EJCG AF Clark, Shaunna L. Aberg, Karolina A. Nerella, Srilaxmi Kumar, Gaurav McClay, Joseph L. Chen, Wenan Xie, Linying Y. Harada, Aki Shabalin, Andrey A. Gao, Guimin Bergen, Sarah E. Hultman, Christina M. Magnusson, Patrik K. E. Sullivan, Patrick F. van den Oord, Edwin J. C. G. TI Combined Whole Methylome and Genomewide Association Study Implicates CNTN4 in Alcohol Use SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Methylation; Next-Generation Sequencing; Genomewide Association Study; CNTN4 ID DNA METHYLATION PATTERNS; WIDE ASSOCIATION; EUROPEAN-AMERICANS; CELL-ADHESION; GENE; DEPENDENCE; BLOOD; HYPERMETHYLATION; SEQUENCE; REGION AB BackgroundMethylome-wide association (MWAS) studies present a new way to advance the search for biological correlates for alcohol use. A challenge with methylation studies of alcohol involves the causal direction of significant methylation-alcohol associations. One way to address this issue is to combine MWAS data with genomewide association study (GWAS) data. MethodsHere, we combined MWAS and GWAS results for alcohol use from 619 individuals. Our MWAS data were generated by next-generation sequencing of the methylated genomic DNA fraction, producing over 60million reads per subject to interrogate methylation levels at similar to 27million autosomal CpG sites in the human genome. Our GWAS included 5,571,786 single nucleotide polymorphisms (SNPs) imputed with 1000 Genomes. ResultsWhen combining the MWAS and GWAS data, our top finding was a region in an intron of CNTN4 (p=2.55x10(-8)), located between chr3: 2,555,403 and 2,555,524, encompassing SNPs rs1382874 and rs1382875. This finding was then replicated in an independent sample of 730 individuals. We used bisulfite pyrosequencing to measure methylation and found significant association with regular alcohol use in the same direction as the MWAS (p=0.021). Rs1382874 and rs1382875 were genotyped and found to be associated in the same direction as the GWAS (p=0.008 and p=0.009). After integrating the MWAS and GWAS findings from the replication sample, we replicated our combined analysis finding (p=0.0017) in CNTN4. ConclusionsThrough combining methylation and SNP data, we have identified CNTN4 as a risk factor for regular alcohol use. C1 [Clark, Shaunna L.; Aberg, Karolina A.; Nerella, Srilaxmi; Kumar, Gaurav; McClay, Joseph L.; Xie, Linying Y.; Harada, Aki; Shabalin, Andrey A.; van den Oord, Edwin J. C. G.] Virginia Commonwealth Univ, Sch Pharm, Ctr Biomarker Res & Precis Med, Richmond, VA USA. [Chen, Wenan; Gao, Guimin] Virginia Commonwealth Univ, Sch Med, Dept Biostat, Richmond, VA USA. [Bergen, Sarah E.] Massachusetts Gen Hosp, Psychiat & Neuro Dev Genet Unit, Boston, MA 02114 USA. [Bergen, Sarah E.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Hultman, Christina M.; Magnusson, Patrik K. E.; Sullivan, Patrick F.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. RP Clark, SL (reprint author), Ctr Biomarker Res & Personalized Med, Sch Pharm, McGuire Hall, Room 216A, POB 980533, Richmond, VA 23298 USA. EM slclark2@vcu.edu RI McClay, Joseph/C-9931-2009; Magnusson, Patrik/C-4458-2017; OI McClay, Joseph/0000-0002-3628-2447; Shabalin, Andrey/0000-0003-0309-6821 FU National Institute on Alcohol Abuse and Alcoholism [K01AA021266]; National Institute of Mental Health [RC2MH089996, 1R01MH097283]; NIMH; Stanley Medical Research Institute FX This study was supported by the National Institute on Alcohol Abuse and Alcoholism (grant K01AA021266) and the National Institute of Mental Health (grants RC2MH089996 and 1R01MH097283). This study is part of a larger project entitled "A Large-Scale Schizophrenia Association Study in Sweden" that is supported by grants from the NIMH and the Stanley Medical Research Institute. Institutions involved in this project are Karolinska Institutet, Icahn School of Medicine at Mount Sinai, University of North Carolina at Chapel Hill, Virginia Commonwealth University, Broad Institute, and the U.S. National Institute of Mental Health. Library construction and next-generation sequencing were performed by EdgeBio, Gaithersburg, MD. NR 52 TC 4 Z9 4 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD AUG PY 2015 VL 39 IS 8 BP 1396 EP 1405 DI 10.1111/acer.12790 PG 10 WC Substance Abuse SC Substance Abuse GA CN7NL UT WOS:000358621200012 PM 26146898 ER PT J AU Froehlich, JC Hausauer, B Fischer, S Wise, B Rasmussen, DD AF Froehlich, Janice C. Hausauer, Brett Fischer, Stephen Wise, Bradley Rasmussen, Dennis D. TI Prazosin Reduces Alcohol Intake in an Animal Model of Alcohol Relapse SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol Preferring Rats; Prazosin; Alcohol Deprivation Effect; Alcohol Relapse ID PREFERRING P RATS; REPEATED DEPRIVATIONS; USE DISORDERS; ALPHA-1-ADRENERGIC ANTAGONIST; ANTIHYPERTENSIVE AGENTS; ESSENTIAL-HYPERTENSION; RECEPTOR ANTAGONIST; ETHANOL DEPRIVATION; PHYSICAL-DEPENDENCE; ANXIETY DISORDERS AB BackgroundMany alcoholics and heavy drinkers undergo repeated cycles of alcohol abstinence followed by relapse to alcohol drinking; a pattern that contributes to escalated alcohol intake over time. In rodents, alcohol drinking that is interspersed with periods of alcohol deprivation (imposed abstinence) increases alcohol intake during reaccess to alcohol. This is termed the alcohol deprivation effect or ADE and is a model of alcohol relapse in humans. We have previously reported that prazosin reduces alcohol drinking during both brief and prolonged treatment in rats selectively bred for alcohol preference (P rats). This study explores whether prazosin prevents alcohol relapse in P rats, as reflected by a reduced or abolished ADE. MethodsAdult male P rats were given 24-hour access to food and water and scheduled access to alcohol (15 and 30% v/v solutions presented concurrently) for 2h/d. After 5weeks, rats underwent imposed alcohol deprivation for 2weeks, followed by alcohol reaccess for 2weeks, and this pattern was repeated for a total of 3 cycles. Rats were injected with prazosin (0, 0.5, 1.0, or 2.0mg/kg body weight, intraperitoneally) once a day for the first 5days of each alcohol reaccess cycle. ResultsAlcohol intake increased on the first day of each alcohol reaccess cycle, demonstrating the formation of an ADE. The ADE was short-lived, lasting only 1day, during each of the 3 cycles. Prazosin, in all doses tested, prevented the expression of an ADE in all 3 alcohol reaccess cycles. ConclusionsPrazosin decreases alcohol intake in P rats even in a situation that would be expected to increase alcohol drinking, namely following periods of alcohol deprivation. This suggests that prazosin may be effective in reducing alcohol relapse that often occurs during attempts to achieve permanent alcohol abstinence in treatment-seeking alcoholics and heavy drinkers. C1 [Froehlich, Janice C.; Hausauer, Brett; Fischer, Stephen; Wise, Bradley] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Rasmussen, Dennis D.] VA Puget Sound Hlth Care Syst, VISN Mental Illness Res Educ & Clin Ctr 20, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. RP Froehlich, JC (reprint author), Indiana Univ Sch Med, 975 West Walnut St IB 424, Indianapolis, IN 46202 USA. EM jcfroehl@iupui.edu FU NIH [AA018604, AA07611, AA13881] FX We thank Dr. Ting-Kai Li and the Indiana Alcohol Research Center for supplying the selectively bred rats used in this study. This work was supported by NIH grants AA018604 (JCF and DDR), AA07611 (JCF), and AA13881 (DDR). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Alcohol Abuse and Alcoholism or the National Institutes of Health. NR 63 TC 7 Z9 7 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD AUG PY 2015 VL 39 IS 8 BP 1538 EP 1546 DI 10.1111/acer.12789 PG 9 WC Substance Abuse SC Substance Abuse GA CN7NL UT WOS:000358621200027 PM 26207767 ER PT J AU Castillo, JJ Olszewski, AJ Kanan, S Meid, K Hunter, ZR Treon, SP AF Castillo, Jorge J. Olszewski, Adam J. Kanan, Sandra Meid, Kirsten Hunter, Zachary R. Treon, Steven P. TI Survival outcomes of secondary cancers in patients with waldenstrom macroglobulinemia: An analysis of the SEER database SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; POPULATION-BASED ANALYSIS; END RESULTS DATABASE; EPIDEMIOLOGY; LYMPHOMA; SURVEILLANCE; MALIGNANCIES; GUIDELINES; DISORDERS; MORTALITY AB We hypothesized that survival outcomes of WM patients who develop SM is distinct from the general population of individuals who develop those same malignancies. Using the SEER-18 data (2000-2011), we identified patients with cancers of the breast, prostate, lung, colorectum, bladder, melanoma, non-Hodgkin lymphoma (NHL), and acute leukemia, and compared their outcomes according to having antecedent WM or not. The outcome of interest was overall survival (OS), which was analyzed in proportional-hazard models adjusted for age, sex, race, and stage. We found that patients with WM who developed SM were older than population controls with those same cancers. In the multivariate analysis, WM cases with colorectal cancer (HR 1.97; P<0.001), melanoma (HR 2.63; P<0.001) and NHL (HR=1.35; P=0.02) had worse OS than controls with those respective cancers. WM patients with diffuse large B-cell lymphoma also had worse OS (HR=1.86; P=0.008). The utilization of surgery and radiation was similar between WM cases and controls, except lower rates of prostatectomy and melanoma surgery among WM patients. The survival of WM patients with colorectal cancer, melanoma, and NHL is worse than among general population controls, arguing in favor of age-appropriate cancer screening. Am. J. Hematol. 90:696-701, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Castillo, Jorge J.; Kanan, Sandra; Meid, Kirsten; 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 Univ, Sch Med, Boston, MA USA. [Olszewski, Adam J.] Brown Univ, Mem Hosp Rhode Isl, Warren Alpert Med Sch, Div Hematol & Oncol, Pawtucket, RI 02860 USA. RP Castillo, JJ (reprint author), 450 Brookline Ave,M221, Boston, MA 02215 USA. EM jorgej_castillo@dfci.harvard.edu OI Olszewski, Adam/0000-0002-6472-6658; Castillo, Jorge/0000-0001-9490-7532; Hunter, Zachary/0000-0002-1689-1691 NR 28 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD AUG PY 2015 VL 90 IS 8 BP 696 EP 701 DI 10.1002/ajh.24052 PG 6 WC Hematology SC Hematology GA CN5QI UT WOS:000358483700065 PM 25963924 ER PT J AU Jinadatha, C Villamaria, FC Restrepo, MI Ganachari-Mallappa, N Liao, IC Stock, EM Copeland, LA Zeber, JE AF Jinadatha, Chetan Villamaria, Frank C. Restrepo, Marcos I. Ganachari-Mallappa, Nagaraja Liao, I-Chia Stock, Eileen M. Copeland, Laurel A. Zeber, John E. TI Is the pulsed xenon ultraviolet light no-touch disinfection system effective on methicillin-resistant Staphylococcus aureus in the absence of manual cleaning? SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article DE Hospital-acquired infections; Supplemental terminal cleaning; Environmental contamination; High touch surfaces ID ACUTE-CARE HOSPITALS; PATHOGENS; DEVICE; DECONTAMINATION; CONTAMINATION; ENVIRONMENT; INFECTIONS; RADIATION; BACTERIA; SURFACES AB Background: Methicillin-resistant Staphylococcus aureus (MRSA) has been shown to survive on ambient surfaces for extended periods of time. Leftover MRSA environmental contamination in a hospital room places future patients at risk. Manual disinfection supplemented by pulsed xenon ultraviolet (PX-UV) light disinfection has been shown to greatly decrease the MRSA bioburden in hospital rooms. However, the effect of PX-UV in the absence of manual disinfection has not been evaluated. Methods: Rooms that were previously occupied by a MRSA-positive patient (current colonization or infection) were selected for the study immediately postdischarge. Five high-touch surfaces were sampled, before and after PX-UV disinfection, in each hospital room. The effectiveness of the PX-UV device on the concentration of MRSA was assessed employing a Wilcoxon signed-rank test for all 70 samples with MRSA in 14 rooms, as well as by surface location. Results: The final analysis included 14 rooms. Before PX-UV disinfection there were a total of 393 MRSA colonies isolated from the 5 high-touch surfaces. There were 100 MRSA colonies after disinfection by the PX-UV device and the overall reduction was statistically significant (P < .01). Conclusions: Our study results suggest that PX-UV light effectively reduces MRSA colony counts in the absence of manual disinfection. These findings are important for hospital and environmental services supervisors who plan to adapt new technologies as an adjunct to routine manual disinfection. Published by Elsevier Inc. on behalf of the Association for Professionals in Infection Control and Epidemiology, Inc. C1 [Jinadatha, Chetan; Villamaria, Frank C.; Ganachari-Mallappa, Nagaraja; Liao, I-Chia; Copeland, Laurel A.; Zeber, John E.] Cent Texas Vet Healthcare Syst, Dept Med, Temple, TX 76504 USA. [Jinadatha, Chetan; Copeland, Laurel A.; Zeber, John E.] Texas A&M Hlth Sci Ctr, Coll Med, Dept Med, Bryan, TX USA. [Villamaria, Frank C.; Liao, I-Chia] Texas A&M Univ, Sch Publ Hlth, College Stn, TX USA. [Restrepo, Marcos I.] South Texas Vet Hlth Care Syst, Dept Med, San Antonio, TX USA. [Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Stock, Eileen M.; Copeland, Laurel A.; Zeber, John E.] Ctr Appl Hlth Res, Temple, TX USA. RP Jinadatha, C (reprint author), Cent Texas Vet Healthcare Syst, Dept Med, 1901 S Vet Dr, Temple, TX 76504 USA. EM chetan.jinadatha@va.gov OI Copeland, Laurel/0000-0002-9478-0209 FU Department of Veterans Affairs [IIR 12-347]; Xenex Healthcare Services, LLC; Central Texas Veterans Health Care System (Temple, Tex); Scott & White Healthcare (Temple, Tex); Center for Applied Health Research (Temple, Tex); National Heart, Lung, and Blood Institute [K23HL096054] FX This work was supported by a Merit Review grant from the Department of Veterans Affairs to JZ (IIR 12-347) and the study's laboratory activity was funded by a grant from Xenex Healthcare Services, LLC. Further, this work was supported by the Central Texas Veterans Health Care System (Temple, Tex), with additional support from Scott & White Healthcare (Temple, Tex) and the jointly sponsored Center for Applied Health Research (Temple, Tex). MIR is partially supported by award No. K23HL096054 from the National Heart, Lung, and Blood Institute. The views expressed in this article are those of the author(s) and do not necessarily represent the views of the Department of Veterans Affairs or the official views of the National Heart, Lung, and Blood Institute or the National Institutes of Health. Xenex Healthcare Service did not participate in the study design or in the collection, analysis, and interpretation of data, the writing of the report, or in the decision to submit the manuscript for publication. The device used in this study is owned by Central Texas Veterans Health Care System. NR 16 TC 3 Z9 3 U1 2 U2 14 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 EI 1527-3296 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD AUG 1 PY 2015 VL 43 IS 8 BP 878 EP 881 DI 10.1016/j.ajic.2015.04.005 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA CN9WY UT WOS:000358802400021 PM 26014583 ER PT J AU Blakney, R Yanke, E Fink, C Wigton, R Safdar, N AF Blakney, Rebekah Yanke, Eric Fink, Cory Wigton, Robert Safdar, Nasia TI Optimizing diagnostic testing for Clostridium difficile: The perceptions of physicians and nurses on when to order testing for C difficile SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article DE Decision-making; Judgement; Healthcare-acquired infection ID INFECTION; ADULTS; OUTBREAK; DIARRHEA; RATES; ODOR AB Physicians and nurses at a single hospital were surveyed on which risk factors were most important in deciding to order Clostridium difficile diagnostic testing. Disagreement between physicians and nurses on the relative importance of several of the risk factors warrants further investigation. Published by Elsevier Inc. on behalf of the Association for Professionals in Infection Control and Epidemiology, Inc. C1 [Blakney, Rebekah; Safdar, Nasia] Univ Wisconsin, Madison Sch Med & Publ Hlth, Dept Med, Madison, WI 53705 USA. [Blakney, Rebekah; Safdar, Nasia] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI 53705 USA. [Yanke, Eric; Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Dept Med, Madison, WI USA. [Fink, Cory] William S Middleton Mem Vet Adm Med Ctr, Coronary Care Unit, Madison, WI USA. [Wigton, Robert] Univ Nebraska Med Ctr, Coll Med, Omaha, NE USA. [Safdar, Nasia] Univ Wisconsin, Sch Med, Dept Med, Infect Dis, Madison, WI 53705 USA. RP Safdar, N (reprint author), Univ Wisconsin, Sch Med, Dept Med, 2500 Overlook Terrace, Madison, WI 53705 USA. EM ns2@medicine.wisc.edu NR 10 TC 0 Z9 0 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 EI 1527-3296 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD AUG 1 PY 2015 VL 43 IS 8 BP 889 EP 891 DI 10.1016/j.ajic.2015.03.025 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA CN9WY UT WOS:000358802400024 PM 25957816 ER PT J AU O'Donnell, AH Toler, TL Dukhovny, SE Eggert, S Weremowicz, S Bieber, FR Tan, WH Lin, AE AF O'Donnell, A. H. Toler, T. L. Dukhovny, S. E. Eggert, S. Weremowicz, S. Bieber, F. R. Tan, W. H. Lin, A. E. TI MONOZYGOTIC TWINS WITH TURNER SYNDROME: DISCORDANT PHENOTYPES BUT CONCORDANT GENOTYPES DUE TO IN UTERO CHIMERISM SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Meeting Abstract CT 35th Annual David W Smith Workshop on Malformations and Morphogenesis CY JUL 25-30, 2014 CL Univ Wisconsin, Madison, WI HO Univ Wisconsin C1 [O'Donnell, A. H.; Tan, W. H.] Boston Childrens Hosp, Boston, MA USA. [Toler, T. L.; Lin, A. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dukhovny, S. E.; Eggert, S.; Weremowicz, S.; Bieber, F. R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [O'Donnell, A. H.; Toler, T. L.; Dukhovny, S. E.; Eggert, S.; Weremowicz, S.; Bieber, F. R.; Tan, W. H.; Lin, A. E.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD AUG PY 2015 VL 167 IS 8 BP 1708 EP 1708 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA CN7ER UT WOS:000358597400059 ER PT J AU Korf, B Ahmadian, R Allanson, J Aoki, Y Bakker, A Wright, EB Denger, B Elgersma, Y Gelb, BD Gripp, KW Kerr, B Kontaridis, M Lazaro, C Linardic, C Lozano, R MacRae, CA Messiaen, L Mulero-Navarro, S Neel, B Plotkin, S Rauen, KA Roberts, A Silva, AJ Sittampalam, SG Zhang, C Schoyer, L AF Korf, Bruce Ahmadian, Reza Allanson, Judith Aoki, Yoko Bakker, Annette Wright, Emma Burkitt Denger, Brian Elgersma, Ype Gelb, Bruce D. Gripp, Karen W. Kerr, Bronwyn Kontaridis, Maria Lazaro, Conxi Linardic, Corinne Lozano, Reymundo MacRae, Calum A. Messiaen, Ludwine Mulero-Navarro, Sonia Neel, Benjamin Plotkin, Scott Rauen, Katherine A. Roberts, Amy Silva, Alcino J. Sittampalam, Sitta G. Zhang, Chao Schoyer, Lisa TI The Third International Meeting on Genetic Disorders in the RAS/MAPK Pathway: Toward a Therapeutic Approach SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE Ras; neurofibromatosis; noonan syndrome; costello syndrome; cardio-facio-cutaneous syndrome ID FACIO-CUTANEOUS SYNDROME; NEUROFIBROMATOSIS TYPE-1; GERMLINE MUTATIONS; COSTELLO-SYNDROME; NOONAN SYNDROME; PHENOTYPE; CANCER; SPECTRUM; GAIN AB "The Third International Meeting on Genetic Disorders in the RAS/MAPK Pathway: Towards a Therapeutic Approach" was held at the Renaissance Orlando at SeaWorld Hotel (August 2-4, 2013). Seventy-one physicians and scientists attended the meeting, and parallel meetings were held by patient advocacy groups (CFC International, Costello Syndrome Family Network, NF Network and Noonan Syndrome Foundation). Parent and patient advocates opened the meeting with a panel discussion to set the stage regarding their hopes and expectations for therapeutic advances. In keeping with the theme on therapeutic development, the sessions followed a progression from description of the phenotype and definition of therapeutic endpoints, to definition of genomic changes, to identification of therapeutic targets in the RAS/MAPK pathway, to preclinical drug development and testing, to clinical trials. These proceedings will review the major points of discussion. (C) 2015 Wiley Periodicals, Inc. C1 [Korf, Bruce; Messiaen, Ludwine] Univ Alabama Birmingham, Birmingham, AL USA. [Ahmadian, Reza] Univ Dusseldorf, Dusseldorf, Germany. [Allanson, Judith] Childrens Hosp Eastern Ontario, Ottawa, ON K1H 8L1, Canada. [Aoki, Yoko] Tohoku Univ, Sch Med, Sendai, Miyagi 980, Japan. [Bakker, Annette] Childrens Tumor Fdn, New York, NY USA. [Wright, Emma Burkitt] Manchester Ctr Genom Med, Manchester, Lancs, England. [Wright, Emma Burkitt] Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Denger, Brian] Parent Project Muscular Dystrophy, Hackensack, NJ USA. [Elgersma, Ype] Erasmus Univ, NL-3000 DR Rotterdam, Netherlands. [Gelb, Bruce D.; Mulero-Navarro, Sonia] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Gripp, Karen W.] Alfred I DuPont Hosp Children, Wilmington, NC USA. [Kerr, Bronwyn] Manchester Ctr Genom Med, Manchester, Lancs, England. [Kontaridis, Maria; MacRae, Calum A.; Roberts, Amy] Harvard Univ, Sch Med, Boston, MA USA. [Kontaridis, Maria] Beth Israel Deaconess Med Canc Ctr, Boston, MA USA. [Lazaro, Conxi] Catalan Inst Oncol ICO IDIBELL, Barcelona, Spain. [Linardic, Corinne] Duke Univ, Sch Med, Durham, NC USA. [Lozano, Reymundo] UC Calif, Davis, CA USA. [MacRae, Calum A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Neel, Benjamin] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada. [Plotkin, Scott] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rauen, Katherine A.] Univ Calif Davis, Davis MIND Inst, Sacramento, CA 95817 USA. [Roberts, Amy] Boston Childrens Hosp, Boston, MA USA. [Silva, Alcino J.] Univ Calif Los Angeles, Los Angeles, CA USA. [Sittampalam, Sitta G.] NIH, NCATS, Baltimore, MD USA. [Zhang, Chao] Plexxikon Inc, Berkeley, CA USA. [Schoyer, Lisa] RASopathies Network USA, Altadena, CA USA. RP Korf, B (reprint author), 230 Kaul Human Genet Bldg,720 20th St South, Birmingham, AL 35294 USA. EM bkorf@uab.edu FU NCI NIH HHS [1R13CA177217-01, R13 CA177217]; NHLBI NIH HHS [R01 HL114775]; NIAMS NIH HHS [R01 AR062165]; NIGMS NIH HHS [T32 GM082773]; NIMH NIH HHS [R01 MH084315] NR 19 TC 1 Z9 1 U1 2 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD AUG PY 2015 VL 167 IS 8 BP 1741 EP 1746 DI 10.1002/ajmg.a.37089 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA CN7ER UT WOS:000358597400134 PM 25900621 ER PT J AU Ge, Y Podrid, PJ Dudzinski, DM AF Ge, Yin Podrid, Philip J. Dudzinski, David M. TI Danger Ahead: Dynamic Hyperacute T Waves SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Ge, Yin] Univ Toronto, Fac Med, Dept Med, Div Cardiol, Toronto, ON, Canada. [Podrid, Philip J.] Boston Univ, Sch Med, Cardiovasc Med Sect, Boston, MA 02118 USA. [Dudzinski, David M.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP Ge, Y (reprint author), Toronto Western Hosp, Div Cardiol, Univ Hlth Network, 399 Bathurst St Ew 5 466, Toronto, ON M5T 2S8, Canada. EM yin.ge2@gmail.com NR 5 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 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD AUG PY 2015 VL 128 IS 8 BP 841 EP 843 DI 10.1016/j.amjmed.2015.04.016 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA CN4GL UT WOS:000358388500028 PM 25912196 ER PT J AU Kang, SK Zhang, A Pandharipande, PV Chandarana, H Braithwaite, RS Littenberg, B AF Kang, Stella K. Zhang, Angela Pandharipande, Pari V. Chandarana, Hersh Braithwaite, R. Scott Littenberg, Benjamin TI DWI for Renal Mass Characterization: Systematic Review and Meta-Analysis of Diagnostic Test Performance SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE diagnostic test accuracy; DWI; meta-analysis; renal mass; systematic review ID APPARENT DIFFUSION-COEFFICIENT; CELL CARCINOMA; NUCLEAR GRADE; WEIGHTED MRI; LESIONS CHARACTERIZATION; SUBTYPE DIFFERENTIATION; PERCUTANEOUS BIOPSY; CLEAR-CELL; B VALUES; ACCURACY AB OBJECTIVE. The objective of our study was to perform a systematic review and metaanalysis of the test performance of DWI in the characterization of renal masses. MATERIALS AND METHODS. We performed searches of three electronic databases for studies on renal mass characterization using DWI. Methodologic quality was assessed for each study. We quantitatively analyzed test performance for three clinical problems: first, benign versus malignant lesions; second, clear cell renal cell carcinoma (RCC) versus other malignancies; and, third, high-versus low-grade clear cell RCCs. We summarized performance as a single pair of sensitivity and specificity values or a summary ROC curve. RESULTS. The studies in the literature were limited in both quantity and quality. For classification of benign versus malignant lesions, four studies with 279 lesions yielded a single summary estimate of 86% sensitivity and 78% specificity. For differentiation of clear cell RCC from other malignancies, five studies showed marked heterogeneity not conducive to meta-analysis. For differentiation of high- from low-grade clear cell RCCs, three studies with 110 lesions showed a threshold effect appropriate for summary ROC construction: The AUC was 0.83. CONCLUSION. Evidence suggests moderate accuracy of DWI for the prediction of malignancy and high- grade clear cell cancers, whereas DWI performance for ascertaining clear cell histologic grade remains unclear. To develop DWI as a noninvasive approach for the evaluation of solid renal masses, prospective studies with standardized test parameters are needed to better establish DWI performance and its impact on patient outcomes. C1 [Kang, Stella K.; Chandarana, Hersh] NYU, Langone Med Ctr, Sch Med, Dept Radiol, New York, NY 10016 USA. [Kang, Stella K.; Braithwaite, R. Scott] NYU, Langone Med Ctr, Sch Med, Dept Populat Hlth, New York, NY 10016 USA. [Zhang, Angela] Harvard Univ, Cambridge, MA 02138 USA. [Pandharipande, Pari V.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Pandharipande, Pari V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Braithwaite, R. Scott] NYU, Langone Med Ctr, Sch Med, Dept Med, New York, NY 10016 USA. [Littenberg, Benjamin] Univ Vermont, Coll Med, Dept Med, Burlington, VT 05405 USA. RP Kang, SK (reprint author), NYU, Langone Med Ctr, Sch Med, Dept Radiol, 550 First Ave, New York, NY 10016 USA. EM stella.kang@nyumc.org RI Kang, Stella/O-7003-2015; OI Chandarana, Hersh/0000-0002-6807-4589; Kang, Stella/0000-0003-2402-3787 FU AUR GE Radiology Research Academic Fellowship Award FX S. K. Kang and this study were supported in part by an AUR GE Radiology Research Academic Fellowship Award. NR 38 TC 11 Z9 12 U1 0 U2 4 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 2015 VL 205 IS 2 BP 317 EP 324 DI 10.2214/AJR.14.13930 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN4YH UT WOS:000358436000030 PM 26204281 ER PT J AU Boutin, RD Chang, J Bateni, C Giza, E Wisner, ER Yaos, L AF Boutin, Robert D. Chang, Jennifer Bateni, Cyrus Giza, Eric Wisner, Erik R. Yaos, Lawrence TI The Notch of Harty (Pseudodefect of the Tibial Plafond): Frequency and Characteristic Findings at MRI of the Ankle SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE ankle; MRI; normal variation; osteochondral lesion ID OSTEOCHONDRAL LESIONS; ARTHROSCOPIC TREATMENT; PITFALL AB OBJECTIVE. The purpose of this study is to report the frequency and characteristic findings of the notch of Harty as seen on MRI. MATERIALS AND METHODS. One hundred six consecutive ankle MRI studies performed at 1.5 or 3 T were reviewed retrospectively by two radiologists. Findings relating to the notch of Harty and ankle joint were recorded and analyzed, including qualitative assessment of the presence of the notch, focal chondral thinning or focal subcortical osteosclerosis at the notch, notch width and depth, osteochondral lesions elsewhere in the ankle, subchondral edema signal or cystic change at the tibial plafond, and the presence of an ankle joint effusion. RESULTS. The study group of 106 patients consisted of 48 male and 58 female patients, with a mean age of 44.5 years (SD, 17.5 years). The notch was identified in 48 of 106 patients (45%) (24 male and 24 female patients; mean age, 43.1 years; range, 7-79 years). When present, the notch averaged 6.2 mm (SD, 1.6 mm) in width and 1.2 mm (SD, 0.5 mm) in depth. The notch was graded as prominent in six of the 106 ankle MRI examinations (6%). Subchondral edemalike signal or cystic change was not localized to the notch in any case. Between patients with versus those without a notch, there was no statistically significant difference in age, sex, subjacent subcortical osteosclerosis, ankle joint effusion, osteochondral lesions elsewhere in the ankle, or subchondral bone marrow edema at the tibial plafond. CONCLUSION. The notch of Harty can be observed as an anatomic variant on MRI and should be differentiated from a traumatic osteochondral lesion. C1 [Boutin, Robert D.; Bateni, Cyrus] Univ Calif Davis, Dept Radiol, Sacramento, CA 95817 USA. [Chang, Jennifer] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Chang, Jennifer] Harvard Univ, Sch Med, Boston, MA USA. [Giza, Eric] Univ Calif Davis, Dept Orthopaed Surg, Sacramento, CA 95817 USA. [Wisner, Erik R.] Univ Calif Davis, Sch Vet Med, Davis, CA 95616 USA. [Yaos, Lawrence] NIH, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. RP Boutin, RD (reprint author), Univ Calif Davis, Dept Radiol, 4860 Y St,Ste 3100, Sacramento, CA 95817 USA. EM robert.boutin@ucdmc.ucdavis.edu NR 23 TC 1 Z9 1 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 2015 VL 205 IS 2 BP 358 EP 362 DI 10.2214/AJR.14.14012 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN4YH UT WOS:000358436000037 PM 26204288 ER PT J AU Dong, F Kojiro, S Borger, DR Growdon, WB Oliva, E AF Dong, Fei Kojiro, Sakiko Borger, Darrell R. Growdon, Whitfield B. Oliva, Esther TI Squamous Cell Carcinoma of the Vulva A Subclassification of 97 Cases by Clinicopathologic, Immunohistochemical, and Molecular Features (p16, p53, and EGFR) SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE vulva; squamous cell carcinoma; human papilloma virus; p16; p53; EGFR; prognosis ID GROWTH-FACTOR RECEPTOR; INTRAEPITHELIAL NEOPLASIA; LICHEN-SCLEROSUS; TP53 MUTATIONS; P16(INK4A) EXPRESSION; DIFFERENTIATED VIN; UNITED-STATES; HPV; CANCER; PATHWAYS AB Squamous cell carcinomas (SCCs) of the vulva develop through human papilloma virus (HPV)-associated or HPV-independent pathways, but the relationship between pathogenesis, classification, and prognosis of these tumors is controversial. Therefore, we review the morphology, immunophenotype, and select molecular features of a consecutive series of 97 patients with vulvar SCC with a median clinical follow-up of 3.6 years. Tumors were histologically classified as basaloid (13), warty (11), mixed basaloid and warty (1), keratinizing (68), nonkeratinizing (3), and sarcomatoid (1). Diffuse p16 expression was associated with younger age at presentation (P<0.0001), basaloid and warty carcinoma subtypes (P<0.0001), and usual vulvar intraepithelial neoplasia (P<0.0001) and was negatively associated with p53 immunopositivity (P=0.0008). Five keratinizing SCCs showed p16 and p53 coexpression, but only 1 was positive for high-risk HPV by in situ hybridization. Among 8 of 36 tumors with EGFR gene amplification, 4 were p53 positive but none p16 positive. In a Cox regression model, early clinical stage (P<0.006), p16 expression (P=0.002), and absent p53 expression (P=0.02) were independent predictors of improved overall survival. These findings utilize morphologic and immunohistochemical analysis to support HPV-associated and HPV-independent pathogenesis of vulvar SCCs and support p16 and p53 immunohistochemistry as markers of disease biology and clinical outcome. C1 [Dong, Fei; Kojiro, Sakiko; Borger, Darrell R.; Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Growdon, Whitfield B.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Oliva, E (reprint author), Massachusetts Gen Hosp, Dept Anat Pathol, 55 Fruit St, Boston, MA 02114 USA. EM eoliva@partners.org NR 39 TC 11 Z9 11 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD AUG PY 2015 VL 39 IS 8 BP 1045 EP 1053 DI 10.1097/PAS.0000000000000454 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA CN4RL UT WOS:000358417800004 PM 26171917 ER PT J AU Lim, D Ip, PPC Cheung, ANY Kiyokawa, T Oliva, E AF Lim, Diana Ip, Philip P. C. Cheung, Annie N. Y. Kiyokawa, Takako Oliva, Esther TI Immunohistochemical Comparison of Ovarian and Uterine Endometrioid Carcinoma, Endometrioid Carcinoma With Clear Cell Change, and Clear Cell Carcinoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE ovarian carcinoma; endometrial carcinoma; endometrioid; endometrioid with clear cells; clear cell; immunohistochemistry ID HEPATOCYTE NUCLEAR FACTOR-1-BETA; GENE-EXPRESSION PROFILES; DISTINCT-HISTOLOGIC-TYPE; GRADE SEROUS CARCINOMA; DIAGNOSTIC-UTILITY; POOR-PROGNOSIS; NAPSIN-A; DIFFERENTIAL-DIAGNOSIS; LUNG ADENOCARCINOMA; PROTEIN EXPRESSION AB Accurate distinction of clear cell carcinoma (CCC) from endometrioid carcinoma (EC) has important clinical implications, but, not infrequently, EC demonstrates clear cell change (EC-CC), mimicking CCC. We examined whether a panel of immunomarkers can help distinguish between these tumors. Sixty-four CCCs (40 ovarian and 24 uterine), 34 ECs (21 ovarian and 13 uterine), and 34 EC-CCs (6 ovarian and 28 uterine) were stained for HNF1, BAF250a, Napsin A, ER, and PR. Intensity and extent of immunoreactivity was assessed. Fifty-seven of 64 (89%) CCCs, 14/34 (41%) EC-CCs, and 16/34 (47%) ECs expressed HNF1, and 56/64 (88%) CCCs, 4/34 (12%) EC-CCs, and 1/34 (3%) ECs stained for Napsin A. Most CCCs demonstrated at least moderate and diffuse staining for both markers, whereas only focal and weak expression was identified in most EC-CC/EC. Compared to HNF1, Napsin A showed increased specificity (93.0% vs. 55.9%, P<0.0001) and similar sensitivity (87.5% vs. 89.1%) in distinguishing CCC from EC-CC/EC. Thirteen of 64 (20%) CCCs, 6/34 (18%) EC-CCs, and 2/34 (6%) ECs showed loss of BAF250a. ER was expressed by 10/64 (16%) CCCs, 30/34 (88%) EC-CCs, and 33/34 (97%) ECs, whereas PR positivity was identified in 9/64 (14%) CCCs, 26/34 (77%) EC-CCs, and 33/34 (97%) ECs. The majority of EC and EC-CC demonstrated diffuse staining for ER/PR, whereas most CCCs showed very focal positivity. There is a statistically significant difference in HNF1, Napsin A, ER, and PR immunoexpression between CCC and EC/EC-CC, with Napsin A being a more specific marker for CCC than HNF1. Overall, the immunoprofile of EC-CC is more comparable to that of EC than CCC. The use of a panel of immunostains can help distinguish EC-CC from CCC. C1 [Lim, Diana] Natl Univ Hlth Syst, Dept Pathol, Singapore, Singapore. [Ip, Philip P. C.; Cheung, Annie N. Y.] Univ Hong Kong, Queen Mary Hosp, Dept Pathol, Hong Kong, Hong Kong, Peoples R China. [Kiyokawa, Takako] Jikei Univ, Sch Med, Dept Pathol, Tokyo, Japan. [Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Oliva, E (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 2, Boston, MA 02114 USA. EM eoliva@partners.org OI , /0000-0002-0493-9838 NR 60 TC 8 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD AUG PY 2015 VL 39 IS 8 BP 1061 EP 1069 DI 10.1097/PAS.0000000000000436 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA CN4RL UT WOS:000358417800006 PM 25871622 ER PT J AU Johncilla, M Misdraji, J Pratt, DS Agoston, AT Lauwers, GY Srivastava, A Doyle, LA AF Johncilla, Melanie Misdraji, Joseph Pratt, Daniel S. Agoston, Agoston T. Lauwers, Gregory Y. Srivastava, Amitabh Doyle, Leona A. TI Ipilimumab-associated Hepatitis Clinicopathologic Characterization in a Series of 11 Cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE hepatitis; ipilimumab; autoimmune; steatohepatitis; drug ID REGULATORY T-CELLS; HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; THERAPY; CANCER; MELANOMA; LIVER; ANTI-CTLA-4; PATHOLOGY; BLOCKADE; CTLA-4 AB Ipilimumab is a monoclonal antibody that inhibits the CTLA4 receptor on cytotoxic T lymphocytes, resulting in immune-mediated tumor cell death. Ipilimumab is most often used in the treatment of metastatic melanoma, and rarely liver toxicity necessitating cessation of treatment occurs. The aim of this study was to characterize the histologic features and clinical course of ipilimumab-associated hepatitis. Eleven patients with clinical suspicion of ipilimumab-induced hepatitis, due to the development of abnormal liver function tests (LFTs) while receiving treatment, and who underwent liver biopsy, were identified over a 6-year period. Ten patients were male and 1 female (median age 58 y), and all received 1 to 4 doses of ipilimumab. None had known preexisting liver disease. Two patients were obese, and another had a history of alcohol abuse. Viral and autoimmune serologies were negative in all patients except 1 who had a mildly elevated ANA titer. Nine biopsies showed active hepatitis with 2 distinct histologic patterns: panlobular hepatitis in 6 cases and zone 3 hepatitis in 3. The inflammatory infiltrate was similar in composition in both patterns, composed predominantly of CD8(+) T lymphocytes, admixed histiocytes, scattered plasma cells, and eosinophils. Prominent histiocytic sinusoidal infiltrates were present in 7 cases and frequently formed loose histiocytic aggregates. Central vein endothelialitis was present in 8 cases. Patients in this group tended to have markedly elevated ALT, AST, and total bilirubin. Two cases did not fit into the above 2 histologic groups: 1 showed portal inflammation with cholangitis, and the other showed morphologic features indistinguishable from nonalcoholic steatohepatitis. Discontinuation of ipilimumab and administration of immunosuppressives resulted in resolution or marked improvement of LFTs in all patients within 3 months of presentation. Ipilimumab may potentially unmask previously subclinical liver disease, for example, fatty liver disease, and the diagnosis of ipilimumab-induced liver injury may only be recognized with certainty after cessation of the drug leads to normalization of LFTs. Overall, ipilimumab-associated hepatitis most often presents with a panlobular active hepatitis that resembles autoimmune hepatitis. Prominent sinusoidal histiocytic infiltrates and central vein damage with endothelialitis may be helpful histologic clues to the diagnosis of ipilimumab-associated hepatitis. C1 [Johncilla, Melanie; Agoston, Agoston T.; Srivastava, Amitabh; Doyle, Leona A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Johncilla, Melanie; Agoston, Agoston T.; Srivastava, Amitabh; Doyle, Leona A.] Harvard Univ, Med Sch, Cambridge, MA 02138 USA. [Misdraji, Joseph; Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Pratt, Daniel S.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. [Pratt, Daniel S.] Harvard Univ, Sch Med, Boston, MA USA. RP Doyle, LA (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM ladoyle@partners.org NR 27 TC 11 Z9 11 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD AUG PY 2015 VL 39 IS 8 BP 1075 EP 1084 DI 10.1097/PAS.0000000000000453 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA CN4RL UT WOS:000358417800008 PM 26034866 ER PT J AU Agoston, AT Zheng, YF Bueno, R Lauwers, GY Odze, RD Srivastava, A AF Agoston, Agoston T. Zheng, Yifan Bueno, Raphael Lauwers, Gregory Y. Odze, Robert D. Srivastava, Amitabh TI Predictors of Disease Recurrence and Survival in Esophageal Adenocarcinomas With Complete Response to Neoadjuvant Therapy SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE esophagus; adenocarcinoma; neoadjuvant therapy; remission; survival; prognosis ID SIGNET-RING CELL; PATHOLOGICAL COMPLETE RESPONSE; LONG-TERM OUTCOMES; PREOPERATIVE CHEMORADIATION; GASTROESOPHAGEAL JUNCTION; ESOPHAGOGASTRIC JUNCTION; PROGNOSTIC-SIGNIFICANCE; ENDOSCOPIC ULTRASOUND; CANCER; CHEMORADIOTHERAPY AB Complete response to neoadjuvant therapy, determined by pathologic examination of the resection specimen (pCR), is associated with a favorable outcome in esophageal adenocarcinomas (EAC), but there is significant heterogeneity in survival reported within this group. Our aim was to determine predictors of disease recurrence (DR) and survival in EAC patients with pCR to neoadjuvant therapy. A total of 93 EAC patients with pCR to neoadjuvant therapy were identified, and a predetermined set of clinicopathologic variables was examined, including patient age, sex, tumor location, pretreatment tumor size, endoscopic ultrasound T and N stage, histologic tumor type, and grade in pretreatment biopsies. The esophagectomy specimens were evaluated for the extent of sampling of the tumor bed, depth of treatment-related changes, presence of treatment effect in lymph nodes, and the total number of lymph nodes examined. Complete histologic examination of the tumor bed was the most significant predictor of favorable outcome for both DR (hazard ratio [HR]=0.42; 95% confidence interval [CI]: 0.21-0.82; P=0.011) and disease-specific mortality (HR=0.40; 95% CI: 0.22-0.70; P<0.01). The presence of a high-grade adenocarcinoma component in pretreatment biopsies (HR=2.19; 95% CI: 1.22-3.94; P<0.01) was associated with a higher disease-specific mortality, and involvement of the gastroesophageal junction (HR=2.37; 95% CI: 1.11-5.06; P=0.026) was associated with a higher rate of DR. Heterogeneity in outcomes for EAC patients with pCR to therapy can be explained by adequacy of histologic examination of the tumor bed, high tumor grade, and involvement of the gastroesophageal junction. C1 [Agoston, Agoston T.; Zheng, Yifan; Bueno, Raphael; Odze, Robert D.; Srivastava, Amitabh] Brigham & Womens Hosp, Boston, MA 02115 USA. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Srivastava, A (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM asrivastava@partners.org NR 42 TC 2 Z9 2 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD AUG PY 2015 VL 39 IS 8 BP 1085 EP 1092 DI 10.1097/PAS.0000000000000420 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA CN4RL UT WOS:000358417800009 PM 26076061 ER PT J AU Cornejo, KM Frazier, L Lee, RS Kozakewich, HPW Young, RH AF Cornejo, Kristine M. Frazier, Lindsay Lee, Richard S. Kozakewich, Harry P. W. Young, Robert H. TI Yolk Sac Tumor of the Testis in Infants and Children A Clinicopathologic Analysis of 33 Cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE yolk sac tumor; endodermal sinus tumor; prepubertal; testis; germ cell tumor; prognosis; treatment ID GERM-CELL TUMORS; PREPUBERTAL TESTICULAR-TUMORS; ENDODERMAL SINUS TUMOR; PEDIATRIC-ONCOLOGY-GROUP; CLINICAL BEHAVIOR; PARATESTICULAR TUMORS; ALPHA-FETOPROTEIN; GASTRIC-CANCER; GUNNAR TEILUM; CLEAR CELLS AB We report 33 pure yolk sac tumors of the testis from boys 5 to 71 months of age (mean 20.7 mo) diagnosed from 1918 to 2014. All except 1 underwent orchiectomy, with lymph node dissections (all negative) performed in 18; 21 also received chemotherapy and 12 radiotherapy. The tumors were 1.6 to 7.0 cm (mean 3.7 cm) and were nonencapsulated, with a gray to yellow, often mucoid, cut surface. The commonest pattern was reticular-microcystic, but macrocystic, papillary, endodermal sinus (Schiller-Duval bodies), labyrinthine, myxomatous, glandular, and solid patterns were also observed. Follow-up was available for 32 patients (mean 100.5 mo; range, 3 to 456 mo). Twenty-four patients (including 4 who did not receive adjuvant therapy) were without evidence of disease, 8 had metastatic disease; 5 of the latter died of tumor and 1 of treatment complications. Two patients with metastasis were cured with radiation with or without chemotherapy. Two or more of the following were associated with a poor outcome in patients presenting with stage I cases: tumor size >4.5 cm (4/6 tumors [67%]), invasion of rete testis and/or epididymis (3/7 tumors [43%]), and necrosis (6/17 tumors [35%]). In the nonmetastasizing group, 2 or more unfavorable features occurred in only 3/24 tumors (13%) (P=0.0001). It is crucial that this tumor be distinguished from the juvenile granulosa cell tumor, which occurs at a slightly younger age and has distinctive features, although there may be some morphologic overlap. The survival of young boys with testicular yolk sac tumor is very good because of both effective chemotherapy and likely, the inherent characteristics of the tumor in this age group. C1 [Cornejo, Kristine M.; Young, Robert H.] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. [Cornejo, Kristine M.; Kozakewich, Harry P. W.; Young, Robert H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. [Lee, Richard S.] Harvard Univ, Sch Med, Dept Urol, Boston, MA USA. [Frazier, Lindsay] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. [Lee, Richard S.] Boston Childrens Hosp, Dept Urol, Boston, MA USA. [Kozakewich, Harry P. W.] Boston Childrens Hosp, Pathol, Boston, MA USA. RP Cornejo, KM (reprint author), UMass Mem Healthcare, Dept Pathol, One Innovation Dr,Biotech 3, Worcester, MA 01605 USA. EM kristine.cornejo@umassmemorial.org NR 102 TC 3 Z9 4 U1 4 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD AUG PY 2015 VL 39 IS 8 BP 1121 EP 1131 DI 10.1097/PAS.0000000000000432 PG 11 WC Pathology; Surgery SC Pathology; Surgery GA CN4RL UT WOS:000358417800013 PM 25828390 ER PT J AU Ting, DT Deshpande, V AF Ting, David T. Deshpande, Vikram TI a Expression of Albumin mRNA in Primary Hepatic Neoplasms and Acinar Cell Carcinoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Letter ID DIFFERENTIATION C1 [Ting, David T.; Deshpande, Vikram] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ting, DT (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. OI Ting, David/0000-0002-3261-2322 NR 3 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD AUG PY 2015 VL 39 IS 8 BP 1157 EP 1158 DI 10.1097/PAS.0000000000000484 PG 2 WC Pathology; Surgery SC Pathology; Surgery GA CN4RL UT WOS:000358417800018 PM 26171921 ER PT J AU He, X Xu, G Liang, W Liu, B Xu, Y Luan, Z Lu, Y Ko, DSC Manyalich, M Schroder, PM Guo, Z AF He, X. Xu, G. Liang, W. Liu, B. Xu, Y. Luan, Z. Lu, Y. Ko, D. S. C. Manyalich, M. Schroder, P. M. Guo, Z. TI Nomogram for Predicting Time to Death After Withdrawal of Life-Sustaining Treatment in Patients With Devastating Neurological Injury SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article ID CARDIAC DEATH; PROSTATE-CANCER; ORGAN DONATION; NEUROCRITICAL PATIENTS; DONORS; VALIDATION; SURVIVAL; CHINA; TRANSPLANTATION; PROGRAM AB Reliable prediction of time of death after withdrawal of life-sustaining treatment in patients with devastating neurological injury is crucial to successful donation after cardiac death. Herein, we conducted a study of 419 neurocritical patients who underwent life support withdrawal at four neurosurgical centers in China. Based on a retrospective cohort, we used multivariate Cox regression analysis to identify prognostic factors for patient death, which were then integrated into a nomogram. The model was calibrated and validated using data from an external retrospective cohort and a prospective cohort. We identified 10 variables that were incorporated into a nomogram. The C-indexes for predicting the 60-min death probability in the training, external validation and prospective validation cohorts were 0.96 (0.93-0.98), 0.94 (0.91-0.97), and 0.99 (0.97-1.00), respectively. The calibration plots after WLST showed an optimal agreement between the prediction of time to death by the nomogram and the actual observation for all cohorts. Then we identified 22, 26 and 37 as cut-points for risk stratification into four groups. Kaplan-Meier curves indicated distinct prognoses between patients in the different risk groups (p<0.001). In conclusion, we have developed and validated a nomogram to accurately identify potential cardiac death donors in neurocritical patients in a Chinese population. C1 [He, X.; Lu, Y.; Guo, Z.] Sun Yat Sen Univ, Affiliated Hosp 1, Organ Transplant Ctr, Guangzhou 510275, Guangdong, Peoples R China. [Xu, G.] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Neurosurg, Guangzhou 510275, Guangdong, Peoples R China. [Liang, W.] Guangzhou Med Univ, Dept Cardiothorac Surg, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China. [Liu, B.] Peoples Hosp Dongguan City, Dept Neurosurg, Dongguan, Dongguan, Peoples R China. [Xu, Y.] First Peoples Hosp Foshan City, Dept Neurosurg, Foshan, Peoples R China. [Luan, Z.] Jiangmen Cent Hosp, Dept Neurosurg, Jiangmen, Peoples R China. [Ko, D. S. C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, Boston, MA USA. [Ko, D. S. C.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Manyalich, M.] TPM DTI Fdn, Barcelona, Spain. [Schroder, P. M.] Univ Toledo, Coll Med, Toledo, OH 43606 USA. RP He, X (reprint author), Sun Yat Sen Univ, Affiliated Hosp 1, Organ Transplant Ctr, Guangzhou 510275, Guangdong, Peoples R China. EM gdtrc@126.com; rockyucsf1981@126.com FU National High Technology Research and Development Program of China (863 Program) [2012AA021008]; National Natural Science Foundation of China [30972951, 81102244, 81102245, 81170448, 81373156]; Special Fund for Science Research by Ministry of Health [201002004, 201302009]; State Key Clinical Specialty Construction Project; Guangdong Provincial Key Laboratory on Organ Donation and Transplant Immunology [2013A061401007] FX This study was supported by the National High Technology Research and Development Program of China (863 Program) (2012AA021008), the National Natural Science Foundation of China (30972951, 81102244, 81102245, 81170448, and 81373156), the Special Fund for Science Research by Ministry of Health (201002004 and 201302009), the State Key Clinical Specialty Construction Project and the Guangdong Provincial Key Laboratory on Organ Donation and Transplant Immunology (2013A061401007). NR 32 TC 4 Z9 4 U1 1 U2 2 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 2015 VL 15 IS 8 BP 2136 EP 2142 DI 10.1111/ajt.13231 PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA CN5XC UT WOS:000358505600016 PM 25810114 ER PT J AU Patel, MS Niemann, CU Sally, MB De La Cruz, S Zatarain, J Ewing, T Crutchfield, M Enestvedt, CK Malinoski, DJ AF Patel, M. S. Niemann, C. U. Sally, M. B. De La Cruz, S. Zatarain, J. Ewing, T. Crutchfield, M. Enestvedt, C. K. Malinoski, D. J. TI The Impact of Hydroxyethyl Starch Use in Deceased Organ Donors on the Development of Delayed Graft Function in Kidney Transplant Recipients: A Propensity-Adjusted Analysis SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article ID NEPHROSIS-LIKE LESIONS; MANAGEMENT GOALS; RENAL-FUNCTION; RESUSCITATION AB Our objective was to evaluate the impact of hydroxyethyl starch (HES) use in organ donors after neurologic determination of death (DNDD) on recipient renal graft outcomes. The following data elements were prospectively collected for every DNDD managed by a single organ procurement organization from June 2011 to July 2013: demographics; critical care endpoints; treatments, including the use of HES; graft cold ischemia time (CIT); and the occurrence of recipient delayed graft function (DGF, dialysis in the first week after transplantation). Logistic regression was performed to identify independent predictors of DGF with a p-value <0.05. The results were then adjusted for each donor's calculated propensity to receive HES. Nine hundred eighty-six kidneys were transplanted from 529 donors. Forty-two percent received HES (1217 +/- 528mL) and 35% developed DGF. Kidneys from DNDDs who received HES had a higher crude rate of DGF (41% vs. 31%, p<0.001). After accounting for the propensity to receive HES, independent predictors of DGF were age (OR 1.02 [1.01-1.04] per year), CIT (OR 1.04[1.02-1.06] per hour), creatinine (OR 1.5 [1.32-1.72] per mg/dL) and HES use (OR 1.41 [1.02-1.95]). HES use during donor management was independently associated with a 41% increase in the risk of DGF in kidney transplant recipients. C1 [Patel, M. S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Niemann, C. U.] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. [Niemann, C. U.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Sally, M. B.; De La Cruz, S.; Crutchfield, M.; Malinoski, D. J.] Portland VA Med Ctr, Surg Crit Care Sect, Portland, OR 97239 USA. [Sally, M. B.; De La Cruz, S.; Enestvedt, C. K.; Malinoski, D. J.] Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97201 USA. [Zatarain, J.] Univ Texas Med Branch, Dept Surg, Galveston, TX 77555 USA. [Ewing, T.] Univ Calif Davis, Sch Med, Davis, CA 95616 USA. RP Malinoski, DJ (reprint author), Portland VA Med Ctr, Surg Crit Care Sect, Portland, OR 97239 USA. EM darren.malinoski@va.gov FU Health Resources and Services Administration [234-2005-37011C, R38OT22183] FX The authors would like to thank all the donors, recipients, staff and leadership of the OneLegacy organ procurement organization. Additionally, this work was supported in part by Health Resources and Services Administration contract 234-2005-37011C and grant R38OT22183. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the U.S. Government. NR 16 TC 4 Z9 4 U1 0 U2 4 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 2015 VL 15 IS 8 BP 2152 EP 2158 DI 10.1111/ajt.13263 PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA CN5XC UT WOS:000358505600018 PM 25904248 ER PT J AU Tonsho, M Lee, S Aoyama, A Boskovic, S Nadazdin, O Capetta, K Smith, RN Colvin, RB Sachs, DH Cosimi, AB Kawai, T Madsen, JC Benichou, G Allan, JS AF Tonsho, M. Lee, S. Aoyama, A. Boskovic, S. Nadazdin, O. Capetta, K. Smith, R. -N. Colvin, R. B. Sachs, D. H. Cosimi, A. B. Kawai, T. Madsen, J. C. Benichou, G. Allan, J. S. TI Tolerance of Lung Allografts Achieved in Nonhuman Primates via Mixed Hematopoietic Chimerism SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article ID MEMORY T-CELLS; TRANSPLANTATION TOLERANCE; INDIRECT ALLORESPONSES; CYNOMOLGUS MACAQUES; POTENTIAL ROLE; INDUCTION; REJECTION; MICE; IMMUNOSUPPRESSION; MAINTENANCE AB While the induction of transient mixed chimerism has tolerized MHC-mismatched renal grafts in nonhuman primates and patients, this approach has not been successful for more immunogenic organs. Here, we describe a modified delayed-tolerance-induction protocol resulting in three out of four monkeys achieving long-term lung allograft survival without ongoing immunosuppression. Two of the tolerant monkeys displayed stable mixed lymphoid chimerism, and the other showed transient chimerism. Serial biopsies and post-mortem specimens from the tolerant monkeys revealed no signs of chronic rejection. The tolerant recipients also exhibited T cell unresponsiveness and a lack of alloantibody. This is the first report of durable mixed chimerism and successful tolerance induction of MHC-mismatched lungs in primates. C1 [Tonsho, M.; Lee, S.; Aoyama, A.; Boskovic, S.; Nadazdin, O.; Capetta, K.; Smith, R. -N.; Colvin, R. B.; Sachs, D. H.; Cosimi, A. B.; Kawai, T.; Madsen, J. C.; Benichou, G.; Allan, J. S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Transplant Ctr, Boston, MA 02115 USA. RP Allan, JS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Transplant Ctr, Boston, MA 02115 USA. EM jallan@partners.org FU NIH grants [P01HL67110, U19AI066705, P01HL018646]; American Society of Transplant Surgeons-Wyeth Collaborative Scientist Award; Yoshida Scholarship Foundation FX This work was supported by NIH grants P01HL67110, U19AI066705, P01HL018646, the American Society of Transplant Surgeons-Wyeth Collaborative Scientist Award (J.S.A) and a Scholarship to Study Abroad from the Yoshida Scholarship Foundation (A.A.). The authors would like to thank Dr. Elisabeth Moeller for providing veterinary care, and the Chugai Pharmaceutical Co. Ltd. for providing tocilizumab under a material transfer agreement with Massachusetts General Hospital. NR 29 TC 6 Z9 7 U1 1 U2 1 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 2015 VL 15 IS 8 BP 2231 EP 2239 DI 10.1111/ajt.13274 PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA CN5XC UT WOS:000358505600028 PM 25904524 ER PT J AU Eikermann-Haerter, K Arbel-Ornath, M Yalcin, N Yu, ES Kuchibhotla, KV Yuzawa, I Hudry, E Willard, CR Climov, M Keles, F Belcher, AM Sengul, B Negro, A Rosen, IA Arreguin, A Ferrari, MD van den Maagdenberg, AMJM Bacskai, BJ Ayata, C AF Eikermann-Haerter, Katharina Arbel-Ornath, Michal Yalcin, Nilufer Yu, Esther S. Kuchibhotla, Kishore V. Yuzawa, Izumi Hudry, Eloise Willard, Carli R. Climov, Mihail Keles, Fatmagul Belcher, Arianna M. Sengul, Buse Negro, Andrea Rosen, Isaac A. Arreguin, Andrea Ferrari, Michel D. van den Maagdenberg, Arn M. J. M. Bacskai, Brian J. Ayata, Cenk TI Abnormal synaptic Ca2+ homeostasis and morphology in cortical neurons of familial hemiplegic migraine type 1 mutant mice SO ANNALS OF NEUROLOGY LA English DT Article ID ACTIN-BASED PLASTICITY; SPREADING DEPRESSION; DENDRITIC SPINES; CACNA1A MUTATION; CALCIUM-CHANNELS; MOUSE MODELS; IN-VIVO; RECEPTOR EXPRESSION; PRESYNAPTIC BOUTONS; ALZHEIMERS-DISEASE AB ObjectiveMigraine is among the most common and debilitating neurological conditions. Familial hemiplegic migraine type 1 (FHM1), a monogenic migraine subtype, is caused by gain-of-function of voltage-gated Ca(V)2.1 calcium channels. FHM1 mice carry human pathogenic mutations in the (1A) subunit of Ca(V)2.1 channels and are highly susceptible to cortical spreading depression (CSD), the electrophysiologic event underlying migraine aura. To date, however, the mechanism underlying increased CSD/migraine susceptibility remains unclear. MethodsWe employed in vivo multiphoton microscopy of the genetically encoded Ca2+-indicator yellow cameleon to investigate synaptic morphology and [Ca2+](i) in FHM1 mice. To study CSD-induced cerebral oligemia, we used in vivo laser speckle flowmetry and multimodal imaging. With electrophysiologic recordings, we investigated the effect of the Ca(V)2.1 gating modifier tert-butyl dihydroquinone on CSD in vivo. ResultsFHM1 mutations elevate neuronal [Ca2+](i) and alter synaptic morphology as a mechanism for enhanced CSD susceptibility that we were able to normalize with a Ca(V)2.1 gating modifier in hyperexcitable FHM1 mice. At the synaptic level, axonal boutons were larger, and dendritic spines were predominantly of the mushroom type, which both provide a structural correlate for enhanced neuronal excitability. Resting neuronal [Ca2+](i) was elevated in FHM1, with loss of compartmentalization between synapses and neuronal shafts. The percentage of calcium-overloaded neurons was increased. Neuronal [Ca2+](i) surge during CSD was faster and larger, and post-CSD oligemia and hemoglobin desaturation were more severe in FHM1 brains. InterpretationOur findings provide a mechanism for enhanced CSD susceptibility in hemiplegic migraine. Abnormal synaptic Ca2+ homeostasis and morphology may contribute to chronic neurodegenerative changes as well as enhanced vulnerability to ischemia in migraineurs. Ann Neurol 2015;78:193-210 C1 [Eikermann-Haerter, Katharina; Yalcin, Nilufer; Yu, Esther S.; Yuzawa, Izumi; Climov, Mihail; Keles, Fatmagul; Sengul, Buse; Negro, Andrea; Rosen, Isaac A.; Arreguin, Andrea; Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurovasc Res Lab,Dept Radiol, Charlestown, MA USA. [Arbel-Ornath, Michal; Kuchibhotla, Kishore V.; Hudry, Eloise; Willard, Carli R.; Belcher, Arianna M.; Bacskai, Brian J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Alzheimer Dis Res Lab,Dept Neurol, Charlestown, MA USA. [Ferrari, Michel D.; van den Maagdenberg, Arn M. J. M.] Leiden Univ, Dept Neurol, Med Ctr, Leiden, Netherlands. [van den Maagdenberg, Arn M. J. M.] Leiden Univ, Dept Human Genet, Med Ctr, Leiden, Netherlands. [Ayata, Cenk] Harvard Univ, Sch Med, Dept Neurol, Stroke Serv,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Ayata, Cenk] Harvard Univ, Sch Med, Dept Neurol, Intens Care Unit,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Eikermann-Haerter, K (reprint author), Massachusetts Gen Hosp, Dept Radiol, Radiol, Neurovasc Res Lab, CNY149, Charlestown, MA 02129 USA. EM khaerter@mgh.harvard.edu FU American Heart Association [10SDG2610275]; NIH [NINDS: NS061505, NS055104, NIBIB: R01000768, S10RR025645]; Harvard Catalyst-Harvard Clinical and Translational Science Center (NIH) [UL1 RR 025758]; Harvard Catalyst-Harvard Clinical and Translational Science Center (Harvard University and its affiliated academic health care centers); Center for Medical Systems Biology (CMSB); Netherlands Genomics Initiative/Netherlands Organization for Scientific Research [050-060-409]; Neuroendovascular Research Fund from the Andrew David Heitman Foundation; Ellison Foundation FX This work was supported by the American Heart Association (10SDG2610275, K.E.-H.), NIH (NINDS: NS061505, NS055104, C.A.; NIBIB: R01000768, S10RR025645, B.J.B.), Harvard Catalyst-Harvard Clinical and Translational Science Center (NIH Award #UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health care centers), Center for Medical Systems Biology (CMSB) established by the Netherlands Genomics Initiative/Netherlands Organization for Scientific Research (project No. 050-060-409, A.M.J.M.v.d.M.), Neuroendovascular Research Fund from the Andrew David Heitman Foundation, C.A and Ellison Foundation, C.A. NR 84 TC 5 Z9 5 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD AUG PY 2015 VL 78 IS 2 BP 193 EP 210 DI 10.1002/ana.24449 PG 18 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CN5WD UT WOS:000358501600005 PM 26032020 ER PT J AU Andrews, JS Trupin, L Schmajuk, G Barton, J Margaretten, M Yazdany, J Yelin, EH Katz, PP AF Andrews, James S. Trupin, Laura Schmajuk, Gabriela Barton, Jennifer Margaretten, Mary Yazdany, Jinoos Yelin, Edward H. Katz, Patricia P. TI Muscle Strength and Changes in Physical Function in Women With Systemic Lupus Erythematosus SO ARTHRITIS CARE & RESEARCH LA English DT Article ID LOWER-EXTREMITY FUNCTION; DUAL-PHOTON ABSORPTIOMETRY; TEST-RETEST RELIABILITY; POPULATION-BASED COHORT; BODY-COMPOSITION; RHEUMATOID-ARTHRITIS; OLDER-ADULTS; ACTIVITY QUESTIONNAIRE; KNEE OSTEOARTHRITIS; SUBSEQUENT DISABILITY AB Objective. Cross-sectional studies have observed that muscle weakness is associated with worse physical function among women with systemic lupus erythematosus (SLE). The present study examines whether reduced upper and lower extremity muscle strength predict declines in function over time among adult women with SLE. Methods. One hundred forty-six women from a longitudinal SLE cohort participated in the study. All measures were collected during in-person research visits approximately 2 years apart. Upper extremity muscle strength was assessed by grip strength. Lower extremity muscle strength was assessed by peak knee torque of extension and flexion. Physical function was assessed using the Short Physical Performance Battery (SPPB). Regression analyses modeled associations of baseline upper and lower extremity muscle strength with followup SPPB scores controlling for baseline SPPB, age, SLE duration, SLE disease activity (Systemic Lupus Activity Questionnaire), physical activity level, prednisone use, body composition, and depression. Secondary analyses tested whether associations of baseline muscle strength with followup in SPPB scores differed between intervals of varying baseline muscle strength. Results. Lower extremity muscle strength strongly predicted changes over 2 years in physical function even when controlling for covariates. The association of reduced lower extremity muscle strength with reduced physical function in the future was greatest among the weakest women. Conclusion. Reduced lower extremity muscle strength predicted clinically significant declines in physical function, especially among the weakest women. Future studies should test whether therapies that promote preservation of lower extremity muscle strength may prevent declines in function among women with SLE. C1 [Andrews, James S.; Trupin, Laura; Schmajuk, Gabriela; Margaretten, Mary; Yazdany, Jinoos; Yelin, Edward H.; Katz, Patricia P.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Schmajuk, Gabriela] VA Med Ctr, San Francisco, CA USA. [Barton, Jennifer] Portland VA Med Ctr, Portland, OR USA. [Barton, Jennifer] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Katz, PP (reprint author), Univ Calif San Francisco, Dept Med, Box 0920, San Francisco, CA 94143 USA. EM patti.katz@ucsf.edu OI Barton, Jennifer/0000-0002-6771-3465 FU NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases [P60-AR-053308]; NIH/National Center for Research Resources University of California San Francisco-Clinical and Translational Science Institute [UL1-RR-024131]; Rosalind Russell Medical Research Center for Arthritis; NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases Academic Rheumatology; Clinical Immunology Training Grant at the University of California, San Francisco FX Supported by the NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant P60-AR-053308), the NIH/National Center for Research Resources University of California, San Francisco-Clinical and Translational Science Institute (grant UL1-RR-024131), and the Rosalind Russell Medical Research Center for Arthritis. Dr. Andrews' work was supported by the NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases Academic Rheumatology and Clinical Immunology Training Grant at the University of California, San Francisco. NR 52 TC 4 Z9 4 U1 3 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD AUG PY 2015 VL 67 IS 8 BP 1070 EP 1077 DI 10.1002/acr.22560 PG 8 WC Rheumatology SC Rheumatology GA CN7LW UT WOS:000358617000005 PM 25623919 ER PT J AU Martin, PJ Lee, SJ Przepiorka, D Horowitz, MM Koreth, J Vogelsang, GB Walker, I Carpenter, PA Griffith, LM Akpek, G Mohty, M Wolff, D Pavletic, SZ Cutler, CS AF Martin, Paul J. Lee, Stephanie J. Przepiorka, Donna Horowitz, Mary M. Koreth, John Vogelsang, Georgia B. Walker, Irwin Carpenter, Paul A. Griffith, Linda M. Akpek, Gorgun Mohty, Mohamad Wolff, Daniel Pavletic, Steven Z. Cutler, Corey S. TI National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: VI. The 2014 Clinical Trial Design Working Group Report SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Chronic graft-versus-host disease; Allogeneic hematopoietic cell transplantation; Clinical trials; Design; Consensus; Guidelines ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; MEASURING THERAPEUTIC RESPONSE; REFRACTORY CHRONIC GVHD; FAILURE-FREE SURVIVAL; ACTIVITY INDEX; EXTRACORPOREAL PHOTOPHERESIS; MARROW-TRANSPLANTATION; PRELIMINARY DEFINITION; RHEUMATOID-ARTHRITIS; AMERICAN-COLLEGE AB Treatment of chronic graft-versus-host disease is intended to produce a sustainable benefit by reducing symptom burden, controlling objective manifestations of disease activity, preventing damage and impairment, and improving overall survival without causing disproportionate harms related to the treatment itself. Successful management can control the disease until systemic treatment is no longer needed. The complexity of the disease, the extended duration of follow-up needed to observe disease resolution and withdrawal of immunosuppressive treatment, and the lack of fully developed shorter term endpoints impede progress in the field. Identification and characterization of primary endpoints demonstrating clinical benefit without requiring years of follow-up is urgently needed, with the understanding that clinical benefit encompasses not only the self-evident benefit of the primary endpoint but also any other associated benefits. This report discusses regulatory considerations, eligibility criteria, the value of controlled trial designs, the merits of proposed primary endpoints, and key considerations elaborated from experience and progress during the past decade. The report concludes by mapping an overall approach that could support and lead to maximally informative clinical trials, especially those that seek to demonstrate clinical benefit along a pathway to regulatory review and approval. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Martin, Paul J.; Lee, Stephanie J.; Carpenter, Paul A.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Przepiorka, Donna] US FDA, Ctr Drug Evaluat Res, Silver Spring, MD USA. [Horowitz, Mary M.] Med Coll Wisconsin, Div Hematol & Oncol, Milwaukee, WI 53226 USA. [Koreth, John; Cutler, Corey S.] Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. [Vogelsang, Georgia B.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. [Walker, Irwin] McMaster Univ, Dept Med, Hamilton, ON, Canada. [Griffith, Linda M.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. [Akpek, Gorgun] Banner MD Anderson Canc Ctr, Stem Cell Transplant Program, Gilbert, AZ USA. [Mohty, Mohamad] Univ Paris 06, Hop St Antoine, INSERM, Clin Hematol & Cellular Therapy Dept,U938, Paris, France. [Wolff, Daniel] Univ Regensburg, Dept Internal Med 3, D-93053 Regensburg, Germany. [Pavletic, Steven Z.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Martin, PJ (reprint author), Fred Hutchinson Canc Res Ctr, D2-100,POB 19024, Seattle, WA 98109 USA. EM pmartin@fredhutch.org OI Martin, Paul/0000-0001-9051-1215 FU NIH: National Cancer Institute (NCI), Center for Cancer Research, Intramural Research Program and Division of Cancer Treatment and Diagnosis, Cancer Therapy Evaluation Program; Office of Rare Disease Research (ORD), National Center for Advancing Translational Sciences; Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases; National Heart, Lung and Blood Institute, Division of Blood Diseases and Resources; NCI, NIH [CA118953, CA18029]; U.S. Department of Health and Human Services FX This project was supported by the NIH: National Cancer Institute (NCI), Center for Cancer Research, Intramural Research Program and Division of Cancer Treatment and Diagnosis, Cancer Therapy Evaluation Program; Office of Rare Disease Research (ORD), National Center for Advancing Translational Sciences; Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases; National Heart, Lung and Blood Institute, Division of Blood Diseases and Resources. Supported by grants CA118953 and CA18029 from the NCI, NIH, and U.S. Department of Health and Human Services (to P.J.M. and S.J.L.). The opinions expressed are those of the authors and do not represent the position of the NCI, the National Heart, Lung and Blood Institute, the National Institute of Allergy and Infectious Diseases, the NIH, the FDA, or the US Government. NR 71 TC 11 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD AUG PY 2015 VL 21 IS 8 BP 1343 EP 1359 DI 10.1016/j.bbmt.2015.05.004 PG 17 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CN6PW UT WOS:000358557700003 PM 25985921 ER PT J AU Vaughn, JE Storer, BE Armand, P Raimondi, R Gibson, C Rambaldi, A Ciceri, F Oneto, R Bruno, B Martin, PJ Sandmaier, BM Storb, R Sorror, ML AF Vaughn, Jennifer E. Storer, Barry E. Armand, Philippe Raimondi, Roberto Gibson, Christopher Rambaldi, Alessandro Ciceri, Fabio Oneto, Rosi Bruno, Benedetto Martin, Paul J. Sandmaier, Brenda M. Storb, Rainer Sorror, Mohamed L. TI Design and Validation of an Augmented Hematopoietic Cell Transplantation-Comorbidity Index Comprising Pretransplant Ferritin, Albumin, and Platelet Count for Prediction of Outcomes after Allogeneic Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Hematopoietic cell transplantation; Biomarkers; HCT-comorbidity index; HCT-CI; Ferritin; Albumin; Platelet count survival ID VERSUS-HOST-DISEASE; LIVER IRON CONTENT; STEM-CELL; SERUM FERRITIN; NONRELAPSE MORTALITY; PROGNOSTIC IMPACT; MYELODYSPLASTIC SYNDROME; MARROW-TRANSPLANTATION; INFERIOR SURVIVAL; RISK-ASSESSMENT AB Pretransplant values of serum ferritin, albumin, and peripheral blood counts were previously suggested to provide prognostic information about hematopoietic cell transplantation (HCT) outcomes. Whether these "biomarkers" have prognostic value independent of each other and the HCT-comorbidity index (HCT-CI) is unknown. We analyzed data from 3917 allogeneic HCT recipients at multiple sites in the United States and Italy using multivariate models including each biomarker and the HCT-CI. Data from all sites were then randomly divided into a training set (n = 2352) to develop weights for the relevant biomarkers to be added to the HCT-CI scores and a validation set (n = 1407) to validate an augmented HCT-CI compared with the original index. Multivariate analysis with data from one site showed that ferritin, albumin, and platelets-not neutrophils or hemoglobin-were independently associated with increased nonrelapse mortality (NRM) and decreased overall survival. Findings were validated in data from the other sites. Subsequently, in a training set from all sites, ferritin >2500 mg/dL (hazard ratio [HR], 1.69); albumin 3 to 3.5 g/dL (HR, 1.61) and <3.0 g/dL (HR, 2.27); and platelets 50 to <100,000 (HR, 1.28), 20 to <50,000 (HR, 1.29), and <20,000 (HR, 1.55) were statistically significantly associated with NRM. Weights were assigned to these laboratory values following the same equation used to design the original index. In the validation set, the addition of the biomarkers to the original index to develop an augmented HCT-CI resulted in a statistically significant increase in a higher c-statistic estimate for prediction of NRM (P = .0007). Ferritin, albumin, and platelet counts are important prognostic markers that further refine the discriminative power of the HCT-CI for transplant outcomes. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Vaughn, Jennifer E.; Martin, Paul J.; Sandmaier, Brenda M.; Storb, Rainer; Sorror, Mohamed L.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Transplantat Biol Program, Seattle, WA 98109 USA. [Vaughn, Jennifer E.; Martin, Paul J.; Sandmaier, Brenda M.; Storb, Rainer; Sorror, Mohamed L.] Univ Washington, Sch Med, Dept Med, Div Med Oncol, Seattle, WA 98195 USA. [Storer, Barry E.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Clin Stat Program, Seattle, WA 98109 USA. [Storer, Barry E.] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. [Armand, Philippe; Gibson, Christopher] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Raimondi, Roberto] S Bortolo Hosp, Dept Hematol, Vicenza, Italy. [Rambaldi, Alessandro] Azienda Osped Papa Giovanni XXIII, Hematol & Bone Marrow Transplant Unit, Bergamo, Italy. [Ciceri, Fabio] Ist Sci San Raffaele, Hematol & BMT Unit, I-20132 Milan, Italy. [Oneto, Rosi] Osped San Martino Genova, Div Hematol, Genoa, Italy. [Bruno, Benedetto] Univ Turin, Dept Hematol Oncol, Turin, Italy. RP Sorror, ML (reprint author), Fred Hutchinson Canc Res Ctr, POB 19024,Mail Stop D5-280, Seattle, WA 98109 USA. EM msorror@fhcrc.org FU National Institutes of Health [HL088021, CA018029, HL036444, CA078902, T32 HL007093-38]; American Cancer Society [RSG-13-084-01-CPHPS]; Patient-Centered Outcome Research Institute [CE-1304-7451] FX This study was supported by grants HL088021, CA018029, HL036444, CA078902, and T32 HL007093-38 from the National Institutes of Health. M.L.S. is also supported by Research Scholar Grant no. RSG-13-084-01-CPHPS from the American Cancer Society and by Patient-Centered Outcome Research Institute Contract no. CE-1304-7451. NR 42 TC 5 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD AUG PY 2015 VL 21 IS 8 BP 1418 EP 1424 DI 10.1016/j.bbmt.2015.04.002 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CN6PW UT WOS:000358557700012 PM 25862589 ER PT J AU Sorror, ML Logan, BR Zhu, XC Rizzo, JD Cooke, KR McCarthy, PL Ho, VT Horowitz, MM Pasquini, MC AF Sorror, Mohamed L. Logan, Brent R. Zhu, Xiaochun Rizzo, J. Douglas Cooke, Kenneth R. McCarthy, Philip L. Ho, Vincent T. Horowitz, Mary M. Pasquini, Marcelo C. TI Prospective Validation of the Predictive Power of the Hematopoietic Cell Transplantation Comorbidity Index: A Center for International Blood and Marrow Transplant Research Study SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Bone marrow transplantation; Hematopoietic cell transplantation; Autologous; Allogeneic; Hematopoietic cell transplantation-comorbidity index; Comorbidities; Validity; Inter-rater reliability ID ACUTE MYELOID-LEUKEMIA; NON-RELAPSE MORTALITY; HCT-CI; REDUCED-INTENSITY; PERFORMANCE STATUS; WEIGHTED KAPPA; HEMATOLOGIC MALIGNANCIES; RISK-ASSESSMENT; DISEASE STATUS; OUTCOMES AB Prospective validation of the hematopoietic cell transplantation-comorbidity index (HCT-CI) using contemporary patients treated with hematopoietic cell transplantation (HCT) across the Unites States is necessary to confirm its widespread applicability. We performed a prospective observational study including all patients (8115 recipients of allogeneic and 11,652 recipients of autologous HCT) who underwent a first HCT that was reported to the Center for International Blood and Marrow Transplant Research between 2007 and 2009. In proportional hazards models, increased HCT-CI scores were independently associated with increases in hazard ratios for nonrelapse mortality (NRM) (P < .0001) and overall mortality (P < .0001) among recipients of allogeneic HCT. HCT-CI scores of >= 3 were uniformly associated with higher risks for outcomes in both allogeneic and autologous HCT and in all subgroups, regardless of diagnoses, age, and conditioning intensity. Recipients of allogeneic HCT with scores of 1 and 2 who were ages < 18 years or were treated with lower intensity conditioning regimens had similar outcomes compared with those with a score of 0. Higher risks for overall mortality, but not for NRM, were observed among recipients of autologous HCT with scores of 1 and 2 versus 0. Our results confirm the validity the HCT-CI in both allogeneic and autologous HCT. The index should be used as a valid standard-of-care health measure in counseling patients for HCT, in clinical trial design, and in adjusting outcome analyses. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Sorror, Mohamed L.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Sorror, Mohamed L.] Univ Washington, Sch Med, Seattle, WA USA. [Logan, Brent R.] Med Coll Wisconsin, Inst Hlth & Soc, Div Biostat, Milwaukee, WI 53226 USA. [Logan, Brent R.; Zhu, Xiaochun; Rizzo, J. Douglas; Horowitz, Mary M.; Pasquini, Marcelo C.] Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Cooke, Kenneth R.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Pediat Blood & Marrow Transplantat Program, Baltimore, MD USA. [McCarthy, Philip L.] Roswell Pk Canc Inst, Dept Med, Blood & Marrow Transplant Program, Buffalo, NY 14263 USA. [Ho, Vincent T.] Dana Farber Canc Inst, Ctr Hematol Oncol, Boston, MA 02115 USA. RP Sorror, ML (reprint author), Fred Hutchinson Canc Res Ctr, Clin Res Div D1 100, 1100 Fairview Ave North, Seattle, WA 98109 USA. EM msorror@fhcrc.org FU National Institutes of Health [HL088021]; American Cancer Society [RSG-13-084-01-CPHPS]; Patient-Centered Outcome Research Institute contract [CE-1304-7451]; Public Health Service from the National Cancer Institute (NCI) [U24-CA076518]; National Heart, Lung, and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases (NIAID); NHLBI [5U10HL069294]; NCI; Health Resources and Services Administration (HRSA/DHHS) [HHSH250201200016C]; Office of Naval Research [N00014-12-1-0142, N00014-13-1-0039]; Actinium Pharmaceuticals; Allos Therapeutics, Inc.; Amgen, Inc.; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; Leukemia & Lymphoma Society; Medac GmbH; Medical College of Wisconsin; Merck Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; Remedy Informatics; Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; TerumoBCT; Teva Neuroscience, Inc.; THERAKOS, Inc.; University of Minnesota; University of Utah; Wellpoint, Inc. FX M.L.S. is supported by grant HL088021 from the National Institutes of Health, #RSG-13-084-01-CPHPS Research Scholar Grant from the American Cancer Society, and a Patient-Centered Outcome Research Institute contract, #CE-1304-7451.; The CIBMTR is supported by Public Health Service grant/cooperative agreement U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a grant/cooperative agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); 2 grants N00014-12-1-0142 and N00014-13-1-0039 from the Office of Naval Research; and grants from *Actinium Pharmaceuticals; Allos Therapeutics, Inc.; *Amgen, Inc.; an anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; *Blue Cross and Blue Shield Association; *Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; *Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; *Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; *Milliman USA, Inc.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; *Remedy Informatics; *Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; *Tarix Pharmaceuticals; *TerumoBCT; *Teva Neuroscience, Inc.; *THERAKOS, Inc.; University of Minnesota; University of Utah; and *Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration or any other agency of the US Government. NR 46 TC 13 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD AUG PY 2015 VL 21 IS 8 BP 1479 EP 1487 DI 10.1016/j.bbmt.2015.04.004 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CN6PW UT WOS:000358557700020 PM 25862591 ER PT J AU Gardner, AJ Tan, CO Ainslie, PN van Donkelaar, P Stanwell, P Levi, CR Iverson, GL AF Gardner, Andrew J. Tan, Can Ozan Ainslie, Philip N. van Donkelaar, Paul Stanwell, Peter Levi, Christopher R. Iverson, Grant L. TI Cerebrovascular reactivity assessed by transcranial Doppler ultrasound in sport-related concussion: a systematic review SO BRITISH JOURNAL OF SPORTS MEDICINE LA English DT Review ID TRAUMATIC BRAIN-INJURY; CARBON-DIOXIDE REACTIVITY; CEREBRAL-BLOOD-FLOW; HEAD-INJURY; CO2 REACTIVITY; NICARDIPINE; VELOCITY; RATS; AUTOREGULATION; FLUNARIZINE AB Background Traumatic brain injury influences regulation of cerebral blood flow in animal models and in human studies. We reviewed the use of transcranial Doppler ultrasound (US) to monitor cerebrovascular reactivity following sport-related concussion. Review method A narrative and systematic review of articles published in the English language, from December 1982 to October 2013. Data sources Articles were retrieved via numerous databases using relevant key terms. Observational, cohort, correlational, cross-sectional and longitudinal studies were included. Results Three publications met the criteria for inclusion; these provided data from 42 athletes and 33 controls. All three studies reported reductions in cerebrovascular reactivity via transcranial Doppler US. Conclusions These initial results support the use of cerebrovascular reactivity as a research tool for identifying altered neurophysiology and monitoring recovery in adult athletes. Larger cross-sectional, prospective and longitudinal studies are required to understand the sensitivity and prognostic value of cerebrovascular reactivity in sport-related concussion. C1 [Gardner, Andrew J.] Univ Newcastle, Sch Med & Publ Hlth, Ctr Translat Neurosci & Mental Hlth, Callaghan, NSW 2308, Australia. [Tan, Can Ozan] Spaulding Rehabil Hosp, Cardiovasc Res Lab, Boston, MA USA. [Tan, Can Ozan] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Ainslie, Philip N.] Ctr Heart Lung & Vasc Hlth, Sch Hlth & Exercise Sci, Fac Hlth & Social Dev, Vancouver, BC, Canada. [Ainslie, Philip N.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [van Donkelaar, Paul] Univ British Columbia, Sch Hlth & Exercise Sci, Fac Hlth & Social Dev, Vancouver, BC V5Z 1M9, Canada. [Stanwell, Peter] Univ Newcastle, Sch Hlth Sci, Fac Hlth, Ctr Translat Neurosci & Mental Hlth, Callaghan, NSW 2308, Australia. [Levi, Christopher R.] Univ Newcastle, Ctr Translat Neurosci & Mental Hlth, Sch Med & Publ Hlth, Callaghan, NSW 2308, Australia. [Iverson, Grant L.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Iverson, Grant L.] MassGen Hosp Children, Sports Concuss Program, Spaulding Rehabil Hosp, Boston, MA USA. [Iverson, Grant L.] Red Sox Fdn, Boston, MA USA. [Iverson, Grant L.] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. RP Gardner, AJ (reprint author), Univ Newcastle, Ctr Translat Neurosci & Mental Hlth, Calvary Mater Hosp, Level 5,McAuley Bldg, Waratah, NSW 2298, Australia. EM andrew.gardner@neurogard.com.au RI Gardner, Andrew/J-5162-2013; Tan, Can Ozan/E-2598-2016; Stanwell, Peter/F-9136-2012; OI Tan, Can Ozan/0000-0001-9673-9907; Stanwell, Peter/0000-0002-4780-0393 FU Australian Football League (AFL); NSW Sporting Injuries Committee; Brain Foundation; Hunter Medical Research Institute; ImPACT Applications, Inc; CNS Vital Signs; Psychological Assessment Resources (PAR, Inc) FX AJG has a clinical practice in neuropsychology involving individuals who have sustained sports-related concussion (including current and former athletes). He has received travel funding from the Australian Football League (AFL) to present at the Concussion in Football Conference in 2013. Previous grant funding includes the NSW Sporting Injuries Committee, the Brain Foundation and the Hunter Medical Research Institute, supported by Jennie Thomas. GI has been reimbursed by the government, professional scientific bodies and commercial organisations for discussing or presenting research relating to mild TBI and sport-related concussion at meetings, scientific conferences and symposiums. He has a clinical and consulting practice in forensic neuropsychology involving individuals who have sustained mild TBIs. He has received research funding from several test publishing companies, including ImPACT Applications, Inc, CNS Vital Signs and Psychological Assessment Resources (PAR, Inc). He is a co-investigator, collaborator, or consultant on grants relating to mild TBI funded by several organisations, including, but not limited to, the Canadian Institute of Health Research, Alcohol Beverage Medical Research Council, Rehabilitation Research and Development (RR&D) Service of the US Department of Veterans Affairs, Vancouver Coastal Health Research Institute and Roche Diagnostics Canada. NR 48 TC 7 Z9 8 U1 3 U2 12 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-3674 EI 1473-0480 J9 BRIT J SPORT MED JI Br. J. Sports Med. PD AUG PY 2015 VL 49 IS 16 BP 1050 EP U42 DI 10.1136/bjsports-2014-093901 PG 7 WC Sport Sciences SC Sport Sciences GA CN8WO UT WOS:000358726600008 PM 25452613 ER PT J AU Sacher, AG Le, LW Lau, A Earle, CC Leighl, NB AF Sacher, Adrian G. Le, Lisa W. Lau, Anthea Earle, Craig C. Leighl, Natasha B. TI Real-world chemotherapy treatment patterns in metastatic non-small cell lung cancer: Are patients undertreated? SO CANCER LA English DT Article DE chemotherapy; health services; metastatic; non-small cell lung cancer (NSCLC); systemic therapy; treatment patterns ID PHASE-III TRIAL; ELDERLY-PATIENTS; RANDOMIZED-TRIAL; DOCETAXEL; CISPLATIN; CARBOPLATIN; CRIZOTINIB; MEDICARE; SURVIVAL; BENEFIT AB BACKGROUNDNew therapies for metastatic non-small cell lung cancer (NSCLC) have improved survival in clinical trials. However, only a minority of patients receive systemic therapy. This article reports treatment patterns and outcomes for a population of Canadian patients with metastatic NSCLC (Ontario). METHODSPatients diagnosed with stage IV NSCLC from 2005 to 2009 were identified through multiple linked provincial databases. Patient demographics, systemic treatment, and survival were examined over time. RESULTSMetastatic NSCLC patients (n=8113) were identified. The median age was 68 years; 39% had adenocarcinoma, 14% had squamous carcinoma, and a higher than expected proportion (43%) had NSCLC not otherwise specified. Only 24% the patients received first-line chemotherapy; only 31% of these received second-line chemotherapy. More patients received systemic therapy over time (from 19% in 2005 to 26% in 2009, P<.0001). Patients who were less than 70 years old or had adenocarcinoma were more likely to receive systemic therapy (P<.0001 for both). The median survival, regardless of age, for those selected to receive first-line cisplatin-gemcitabine chemotherapy was longer than that for those receiving other nonpemetrexed platinum doublets at 11.6 months (P=.0002). Patients with nonsquamous histology who were treated with second-line pemetrexed had longer median survival than those treated with docetaxel (19.8 vs 14.1 months, P<.0001). CONCLUSIONSMost patients with metastatic NSCLC in the general population still do not receive systemic therapy. Those selected for first- and second-line systemic treatment, including older patients, have survival outcomes comparable to clinical trial results. Older patients and patients with squamous histology are less likely to receive chemotherapy. The low levels of treatment utilization in this study warrant further investigation. Cancer 2015;121:2562-2569. (c) 2015 American Cancer Society. Most patients with metastatic non-small cell lung cancer in the general population still do not receive systemic therapy. C1 [Sacher, Adrian G.; Le, Lisa W.; Lau, Anthea; Leighl, Natasha B.] Univ Hlth Network, Princess Margaret Canc Ctr, Div Med Oncol, Toronto, ON M5G 2M9, Canada. [Sacher, Adrian G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Sacher, Adrian G.; Earle, Craig C.; Leighl, Natasha B.] Univ Toronto, Fac Med, Toronto, ON, Canada. [Le, Lisa W.; Lau, Anthea] Univ Hlth Network, Dept Biostat, Princess Margaret Canc Ctr, Toronto, ON M5G 2M9, Canada. [Earle, Craig C.] Inst Clin Evaluat Sci, Toronto, ON, Canada. RP Leighl, NB (reprint author), Univ Hlth Network, Princess Margaret Canc Ctr, Div Med Oncol, 5-105 610 Univ Ave, Toronto, ON M5G 2M9, Canada. EM natasha.leighl@uhn.ca RI Sacher, Adrian/I-8080-2016 OI Sacher, Adrian/0000-0001-7865-2701 FU Division of Medical Oncology of Princess Margaret Hospital/University Health Network FX This study was supported by the Division of Medical Oncology of Princess Margaret Hospital/University Health Network. NR 26 TC 11 Z9 11 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD AUG 1 PY 2015 VL 121 IS 15 BP 2562 EP 2569 DI 10.1002/cncr.29386 PG 8 WC Oncology SC Oncology GA CN5ZA UT WOS:000358511600012 PM 25891153 ER PT J AU Lo, PC Dahlberg, SE Nishino, M Johnson, BE Sequist, LV Jackman, DM Janne, PA Oxnard, GR AF Lo, Peter C. Dahlberg, Suzanne E. Nishino, Mizuki Johnson, Bruce E. Sequist, Lecia V. Jackman, David M. Jaenne, Pasi A. Oxnard, Geoffrey R. TI Delay of treatment change after objective progression on first-line erlotinib in epidermal growth factor receptor-mutant lung cancer SO CANCER LA English DT Article DE disease progression; epidermal growth factor receptor mutation; erlotinib; non-small cell lung cancer; time until treatment change ID TYROSINE KINASE INHIBITORS; DISEASE-CONTROL; TRIAL; CHEMOTHERAPY; STRATEGY; EVALUATE; THERAPY; FAILURE AB BACKGROUNDErlotinib is a highly active epidermal growth factor receptor (EGFR) kinase inhibitor that is approved for first-line use in lung cancers harboring EGFR mutations. Anecdotal experience suggests that this drug may provide continued disease control after patients develop objective progression of disease (PD), although this has not been systematically studied to date. METHODSPatients who had Response Evaluation Criteria In Solid Tumors-defined PD who were participating in 3 prospective trials of first-line erlotinib in advanced lung cancer were studied retrospectively, and the progression characteristics were compared between patients with and without EGFR-sensitizing mutations. Factors were studied that influenced the time until treatment change (TTC), defined as the time from PD to the start of a new systemic therapy or death. The rate of tumor progression was assessed by comparing tumor measurements between the computed tomography scan obtained at the time of PD and the preceding scan. RESULTSIn total, 92 eligible patients were studied, including 42 with and 50 without an EGFR-sensitizing mutation. The EGFR-mutant cohort had a slower rate of progression (P=.003) and a longer TTC (P<.001). Among the patients with EGFR-mutant cancers, 28 (66%) continued single-agent erlotinib after PD, and 21 (50%) were able to delay a change in systemic therapy for >3 months; only 2 patients received local debulking therapy during that period. Multivariate analysis of the patients with EGFR-mutant tumors demonstrated that a longer time to progression, a slower rate of progression, and a lack of new extrathoracic metastases were associated with a longer TTC. CONCLUSIONSA change in systemic therapy commonly can be delayed in patients with EGFR-mutant lung cancer who objectively progress on first-line erlotinib, particularly in those with a longer time to progression, a slow rate of progression, and a lack of new extrathoracic metastases. Cancer 2015;121:2570-2577. (c) 2015 American Cancer Society. Anecdotal experience suggests that some patients with non-small cell lung cancer who progress on erlotinib can have continued disease control without a change in treatment. In this analysis, investigators study 92 patients with non-small cell lung cancer who develop objective disease progression while receiving first-line erlotinib on 3 clinical trials and demonstrate the potential benefits of delaying a change in treatment for patients who have epidermal growth factor receptor-mutant lung cancer and favorable progression characteristics. C1 [Lo, Peter C.; Johnson, Bruce E.; Jackman, David M.; Jaenne, Pasi A.; Oxnard, Geoffrey R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02114 USA. [Dahlberg, Suzanne E.] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02114 USA. [Dahlberg, Suzanne E.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Nishino, Mizuki] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02114 USA. [Nishino, Mizuki; Johnson, Bruce E.; Sequist, Lecia V.; Jackman, David M.; Jaenne, Pasi A.; Oxnard, Geoffrey R.] Harvard Univ, Sch Med, Boston, MA USA. [Johnson, Bruce E.; Jackman, David M.; Jaenne, Pasi A.; Oxnard, Geoffrey R.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Sequist, Lecia V.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Jaenne, Pasi A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02114 USA. RP Oxnard, GR (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 450 Brookline Ave,D1234, Boston, MA 02114 USA. EM geoffrey_oxnard@dfci.harvard.edu FU National Cancer Institute at the National Institutes of Health [P50-CA090578, R01-CA114465, K23-CA157631]; Conquer Cancer Foundation of the American Society of Clinical Oncology; Gallup donor funds FX This work was supported in part by the National Cancer Institute at the National Institutes of Health (P50-CA090578, R01-CA114465, K23-CA157631); by a grant from the Conquer Cancer Foundation of the American Society of Clinical Oncology; and by the Gallup donor funds. NR 17 TC 12 Z9 12 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD AUG 1 PY 2015 VL 121 IS 15 BP 2570 EP 2577 DI 10.1002/cncr.29397 PG 8 WC Oncology SC Oncology GA CN5ZA UT WOS:000358511600013 PM 25876525 ER PT J AU Galsky, MD Pal, SK Chowdhury, S Harshman, LC Crabb, SJ Wong, YN Yu, EY Powles, T Moshier, EL Ladoire, S Hussain, SA Agarwal, N Vaishampayan, UN Recine, F Berthold, D Necchi, A Theodore, C Milowsky, MI Bellmunt, J Rosenberg, JE AF Galsky, Matthew D. Pal, Sumanta K. Chowdhury, Simon Harshman, Lauren C. Crabb, Simon J. Wong, Yu-Ning Yu, Evan Y. Powles, Thomas Moshier, Erin L. Ladoire, Sylvain Hussain, Syed A. Agarwal, Neeraj Vaishampayan, Ulka N. Recine, Federica Berthold, Dominik Necchi, Andrea Theodore, Christine Milowsky, Matthew I. Bellmunt, Joaquim Rosenberg, Jonathan E. CA Retrospective Int Study Canc Uroth TI Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle-invasive bladder cancer SO CANCER LA English DT Article DE bladder cancer; cisplatin; gemcitabine plus cisplatin; methotrexate; vinblastine; doxorubicin; plus cisplatin; muscle invasion; neoadjuvant ID ADVANCED UROTHELIAL CARCINOMA; PHASE-III TRIAL; ACCELERATED METHOTREXATE; RETROSPECTIVE ANALYSIS; CLINICAL-OUTCOMES; PROPENSITY SCORE; CHEMOTHERAPY; MULTICENTER; MANAGEMENT; CYSTECTOMY AB BACKGROUNDGemcitabine plus cisplatin (GC) has been adopted as a neoadjuvant regimen for muscle-invasive bladder cancer despite the lack of Level I evidence in this setting. METHODSData were collected using an electronic data-capture platform from 28 international centers. Eligible patients had clinical T-classification 2 (cT2) through cT4aN0M0 urothelial cancer of the bladder and received neoadjuvant GC or methotrexate, vinblastine, doxorubicin, plus cisplatin (MVAC) before undergoing cystectomy. Logistic regression was used to compute propensity scores as the predicted probabilities of patients being assigned to MVAC versus GC given their baseline characteristics. These propensity scores were then included in a new logistic regression model to estimate an adjusted odds ratio comparing the odds of attaining a pathologic complete response (pCR) between patients who received MVAC and those who received GC. RESULTSIn total, 212 patients (146 patients in the GC cohort and 66 patients in the MVAC cohort) met criteria for inclusion in the analysis. The majority of patients in the MVAC cohort (77%) received dose-dense MVAC. The median age of patients was 63 years, they were predominantly men (74%), and they received a median of 3 cycles of neoadjuvant chemotherapy. The pCR rate was 29% in the MVAC cohort and 31% in the GC cohort. There was no significant difference in the pCR rate when adjusted for propensity scores between the 2 regimens (odds ratio, 0.91; 95% confidence interval, 0.48-1.72; P=.77). In an exploratory analysis evaluating survival, the hazard ratio comparing hazard rates for MVAC versus GC adjusted for propensity scores was not statistically significant (hazard ratio, 0.78; 95% confidence interval, 0.40-1.54; P=.48). CONCLUSIONSPatients who received neoadjuvant GC and MVAC achieved comparable pCR rates in the current analysis, providing evidence to support what has become routine practice. Cancer 2015;121:2586-2593. (c) 2015 American Cancer Society. The use of neoadjuvant cisplatin-based chemotherapy for muscle-invasive bladder cancer is supported by randomized, phase 3 studies. The current analysis, which includes more than 200 patients, supports the use of cisplatin with gemcitabine as an alternative regimen to methotrexate, vinblastine, doxorubicin, and cisplatin. C1 [Galsky, Matthew D.] Mt Sinai Med Ctr, Dept Hematol & Med Oncol, New York, NY 10029 USA. [Pal, Sumanta K.] City Hope Comprehens Canc Ctr, Dept Med Oncol & Expt Therapeut, Duarte, CA USA. [Chowdhury, Simon] Guys & St Thomas Hosp, Dept Urol, London SE1 9RT, England. [Harshman, Lauren C.; Bellmunt, Joaquim] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Crabb, Simon J.] Southampton Gen Hosp, Dept Med Oncol, Southampton SO9 4XY, Hants, England. [Wong, Yu-Ning] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. [Yu, Evan Y.] Fred Hutchinson Canc Res Ctr, Dept Med, Div Oncol, Seattle, WA 98104 USA. [Powles, Thomas] Barts Canc Inst, Dept Med Oncol, London, England. [Moshier, Erin L.] Mt Sinai Med Ctr, Div Biostat, Dept Preventat Med, New York, NY 10029 USA. [Ladoire, Sylvain] Georges Francois Leclerc Ctr, Dept Med Oncol, Dijon, France. [Hussain, Syed A.] Univ Liverpool, Inst Translat Med, Dept Mol & Clin Canc Med, Liverpool L69 3BX, Merseyside, England. [Agarwal, Neeraj] Univ Utah, Huntsman Canc Inst, Dept Med Oncol, Salt Lake City, UT USA. [Vaishampayan, Ulka N.] Barbara Ann Karmanos Canc Ctr, Dept Hematol & Oncol, Detroit, MI USA. [Recine, Federica] Samuel & Barbara Sternberg Canc Res Fdn, Dept Med Oncol, Rome, Italy. [Berthold, Dominik] Univ Lausanne Hosp, Dept Med Oncol, Lausanne, Switzerland. [Necchi, Andrea] Fdn IRCCS Natl Canc Inst, Dept Med Oncol, Milan, Italy. [Theodore, Christine] Hosp Foch, Dept Oncol, Suresnes, France. [Milowsky, Matthew I.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Med, Div Hematol & Oncol, Chapel Hill, NC 27599 USA. [Rosenberg, Jonathan E.] Mem Sloan Kettering Canc Ctr, Dept Med, Div Genitourinary Oncol, New York, NY 10021 USA. RP Galsky, MD (reprint author), Mt Sinai Sch Med, Tisch Canc Inst, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM matthew.galsky@mssm.edu OI Niegisch, Gunter/0000-0001-6929-8691; Rosenberg, Jonathan/0000-0003-2637-4249; Necchi, Andrea/0000-0002-3007-2756; Crabb, Simon/0000-0003-3521-9064 FU Bristol-Myers Squibb; Novartis AG; Celgene Corporation; BioMotiv; Merck Company Inc; AstraZeneca; Janssen Pharmaceuticals Inc; Astellas Pharma US Inc; Dendreon Corporation; Sanofi; Pfizer Inc; ImClone (an Eli Lilly company); Roche; Astellas Pharma US Inc.; Bayer; Pierre Fabre FX Dr. Galsky reports grants from Bristol-Myers Squibb, Novartis AG, and Celgene Corporation and advisory/consulting fees from BioMotiv and Merck & Company Inc; he is a cofounder of Dual Therapeutics. Dr. Crabb reports grants for research funding from AstraZeneca and advisory/speakers' fees from Janssen Pharmaceuticals Inc, Astellas Pharma US Inc, Dendreon Corporation, and Sanofi. Dr. Wong reports a grant from Pfizer Inc for an unrelated project and institutional clinical trial support from Bayer, Astellas Pharma US Inc, Jansen Pharmaceuticals Inc, and Millennium Pharmaceuticals. Dr. Yu reports grants from ImClone (an Eli Lilly company) for a sponsored clinical trial. Dr. Powles was supported by grants from Roche, Bristol-Myers Squibb, and Astellas Pharma US Inc. Dr. Hussain reports grants from Bayer, Pierre Fabre, and Boehringer Ingelheim; advisory/consulting fees from Astellas Pharma US Inc, Bayer, and Pierre Fabre; and meeting support from Janssen Pharmaceuticals and Boehringer Ingelheim. Dr. Bellmunt reports lecture fees from Pierre Fabre; he serves without compensation on the advisory boards of Pierre Fabre, Genentech, and Merck & Company Inc, and he is an uncompensated lecturer for Merck & Company Inc. NR 34 TC 18 Z9 19 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD AUG 1 PY 2015 VL 121 IS 15 BP 2586 EP 2593 DI 10.1002/cncr.29387 PG 8 WC Oncology SC Oncology GA CN5ZA UT WOS:000358511600015 PM 25872978 ER PT J AU Keane, FK Chen, YH Neville, BA Tishler, RB Schoenfeld, JD Catalano, PJ Margalit, DN AF Keane, Florence K. Chen, Yui-Hui Neville, Bridget A. Tishler, Roy B. Schoenfeld, Jonathan D. Catalano, Paul J. Margalit, Danielle N. TI Changing prognostic significance of tumor stage and nodal stage in patients with squamous cell carcinoma of the oropharynx in the human papillomavirus era SO CANCER LA English DT Article DE American Joint Committee on Cancer (AJCC) cancer staging; carcinoma; head and neck cancer; human papilloma virus; oropharyngeal cancer; squamous cell ID UNITED-STATES; NECK-CANCER; SURVIVAL; HEAD; METASTASIS; OUTCOMES; RISK; RADIOTHERAPY; MODELS AB BACKGROUNDAlthough human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) tends to present at an advanced nodal stage (N stage), the prognosis is generally better than that for HPV-negative OPSCC. Prior work has demonstrated the increasing incidence of HPV-related OPSCC in the United States. This study was designed to determine whether the changing epidemiology of OPSCC is reflected in changes in the prognostic significance of the tumor stage (T stage) and the N stage in a population-based cohort. METHODSThe Surveillance, Epidemiology, and End Results program was used to identify 13,328 patients who were 18 years old or older and were diagnosed with OPSCC from 1997 to 2008. The Kaplan-Meier method was used to estimate head and neck cancer-specific survival. Cox proportional hazards models were used to evaluate the associations between head and neck cancer-specific mortality (HNCSM) and T and N stages and the interaction of variables with the year of diagnosis. RESULTSWith a median follow-up of 67 months, there were 4099 head and neck cancer deaths. There was a significant interaction between the T stage and time (P for interaction=.01), with the effect of the T stage on HNCSM increasing from 1997 to 2008. The T stage retained a linear relationship with HNCSM. The effect of the N stage on HNCSM declined over time (P for interaction=.0004). The current American Joint Committee on Cancer (AJCC) staging system did not subdivide distinct prognostic subgroups for HNCSM by overall stage. CONCLUSIONSIn this population-based study of OPSCC, the effect of the N stage on cancer-specific mortality decreased over time as the impact of the T stage increased. The current AJCC staging system did not distinguish prognostic subgroups. These changes may reflect the increasing prevalence of HPV-related OPSCC. Further study in HPV-defined cohorts is needed to tailor the AJCC staging system to better reflect HNCSM risk. Cancer 2015;121:2594-2602. (c) 2015 American Cancer Society. This population-based analysis demonstrates that the prognostic significance of tumor and nodal stages has changed significantly over time among patients with oropharyngeal cancer, and the current American Joint Committee on Cancer (AJCC) staging system does not consistently distinguish prognostic subgroups. These findings likely reflect the changing demographics of oropharyngeal squamous cell carcinoma and support current efforts to update the AJCC staging system for oropharyngeal cancer. C1 [Keane, Florence K.] Harvard Radiat Oncol Program, Boston, MA USA. [Chen, Yui-Hui; Catalano, Paul J.] Dana Farber Harvard Canc Ctr, Dept Biostat & Computat Biol, Boston, MA USA. [Neville, Bridget A.] Ariadne Labs, Boston, MA USA. [Tishler, Roy B.; Schoenfeld, Jonathan D.; Margalit, Danielle N.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Margalit, DN (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM dmargalit@lroc.harvard.edu NR 36 TC 10 Z9 10 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD AUG 1 PY 2015 VL 121 IS 15 BP 2594 EP 2602 DI 10.1002/cncr.29402 PG 9 WC Oncology SC Oncology GA CN5ZA UT WOS:000358511600016 PM 25873094 ER PT J AU McKay, RR Gray, KP Hayes, JH Bubley, GJ Rosenberg, JE Hussain, A Kantoff, PW Taplin, ME AF McKay, Rana R. Gray, Kathryn P. Hayes, Julia H. Bubley, Glenn J. Rosenberg, Jonathan E. Hussain, Arif Kantoff, Philip W. Taplin, Mary-Ellen TI Docetaxel, bevacizumab, and androgen deprivation therapy for biochemical disease recurrence after definitive local therapy for prostate cancer SO CANCER LA English DT Article DE androgen deprivation therapy; bevacizumab; biochemical disease recurrence; docetaxel; prostate cancer ID TERM-FOLLOW-UP; RADICAL PROSTATECTOMY; NATURAL-HISTORY; HORMONE-THERAPY; MEN; PROGRESSION; ANTIGEN; TRIAL AB BACKGROUNDPatients with biochemical disease recurrence (BCR) after definitive treatment for prostate cancer comprise a heterogeneous population for whom standard therapy options are lacking. The purpose of the current trial was to evaluate the feasibility, toxicity, and efficacy of early multimodality systemic therapy in men with BCR. METHODSEligible patients had an increasing prostate-specific antigen (PSA) level, a PSA doubling time 10 months, and no evidence of metastases after radical prostatectomy (RP) and/or radiotherapy (RT) for localized disease. Treatment consisted of docetaxel at a dose of 75 mg/m(2) every 3 weeks for 4 cycles, bevacizumab at a dose of 15 mg/kg every 3 weeks for 8 cycles, and androgen deprivation therapy (ADT) for 18 months. The primary endpoint was the percentage of patients who were free from PSA progression 1 year after the completion of therapy. RESULTSA total of 41 patients were included in the analysis. At 1 year after the completion of ADT, 45% of patients (13 of 29 patients) and 29% of patients (5 of 17 patients) with a testosterone level 100 ng/dL and 240 ng/dL, respectively, had a PSA <0.2 ng/mL. The median follow-up was 27.5 months (interquartile range, 21.8-38.1 months). Eight patients (20%) were free from PSA progression, 19 patients (46%) did not reinitiate ADT, and 34 patients (83%) were free from metastasis. Sixteen patients (39%) experienced grade 3 and 5 patients (12%) experienced grade 4 toxicities (toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0]). CONCLUSIONSMultimodality systemic therapy with docetaxel, bevacizumab, and ADT is feasible and produces PSA responses in men with BCR. Long-term follow-up is needed to determine the percentage of patients with a durable PSA response who are able to avoid having to reinitiate prostate cancer therapy. Cancer 2015;121:2603-2611. (c) 2015 American Cancer Society. We demonstrate that multimodality systemic therapy with docetaxel, bevacizumab, and ADT produces favorable PSA responses in men with BCR following definitive PC therapy. At a median follow up of 27.5 months, 46% of patients have not reinitiated ADT and 92% have a testosterone = 100 ng/dL. C1 [McKay, Rana R.; Gray, Kathryn P.; Hayes, Julia H.; Kantoff, Philip W.; Taplin, Mary-Ellen] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Bubley, Glenn J.] Beth Israel Deaconess Med Ctr, Genitourinary Med Oncol, Boston, MA 02215 USA. [Rosenberg, Jonathan E.] Mem Sloan Kettering Canc Ctr, Dept Med, Div Solid Tumor Oncol, New York, NY 10021 USA. [Hussain, Arif] Greenebaum Canc Ctr, Med Oncol Hematol Program, Baltimore, MD USA. RP Taplin, ME (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM mtaplin@partners.org OI Rosenberg, Jonathan/0000-0003-2637-4249 FU Genentech FX Supported by Genentech. NR 16 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD AUG 1 PY 2015 VL 121 IS 15 BP 2603 EP 2611 DI 10.1002/cncr.29398 PG 9 WC Oncology SC Oncology GA CN5ZA UT WOS:000358511600017 PM 25903013 ER PT J AU Matulonis, U Berlin, S Lee, H Whalen, C Obermayer, E Penson, R Liu, J Campos, S Krasner, C Horowitz, N AF Matulonis, Ursula Berlin, Suzanne Lee, Hang Whalen, Christin Obermayer, Elizabeth Penson, Richard Liu, Joyce Campos, Susana Krasner, Carolyn Horowitz, Neil TI Phase I study of combination of vorinostat, carboplatin, and gemcitabine in women with recurrent, platinum-sensitive epithelial ovarian, fallopian tube, or peritoneal cancer SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Ovarian cancer; HDAC inhibitors; Vorinostat; Platinum sensitive ID HISTONE DEACETYLASE INHIBITORS; SUBEROYLANILIDE HYDROXAMIC ACID; OLAPARIB MAINTENANCE THERAPY; GYNECOLOGIC-ONCOLOGY-GROUP; III TRIAL; PACLITAXEL; CARCINOMA; SAHA; CHEMOTHERAPY; BELINOSTAT AB Combining histone deacetylase inhibitors and chemotherapy is synergistic. This phase I study combined escalating vorinostat doses with constant doses of carboplatin and gemcitabine for the treatment of recurrent platinum-sensitive ovarian cancer. The objectives of this study were to determine the maximally tolerated dose of this combination; secondary objectives included preliminary response rate of this regimen and toxicity profile. Fifteen patients with relapsed ovarian cancer were enrolled into this phase I study. Doses of carboplatin and gemcitabine were AUC 4 on day 1 and 1000 mg/m(2) on days 1 and 8, respectively; cycles were administered every 21 days. Vorinostat was tested using four different schedules. The first dose level (DL A) tested vorinostat as daily oral dosing from days 1 to 14. DL B tested twice daily (BID) vorinostat dosing on days 1-3 and 8-10. DL C tested BID vorinostat dosing on days 1, 2, 8, and 9, starting vorinostat 1 day prior to initiation of carboplatin and gemcitabine, and DL D tested vorinostat on days 1 and 2 with chemotherapy starting on day 2. All four DLs tested resulted in dose-limiting toxicities, and no MTD was determined. Toxicities were mostly hematologic. Seven patients were evaluable for RECIST assessment, and six of them had partial responses (PR) via RECIST. Combination of carboplatin, gemcitabine, and vorinostat has activity in relapsed platinum-sensitive ovarian cancer, but was difficult to combine because of hematologic toxicities in this phase I study. No maximally tolerated dose was found, and the study was terminated early. C1 [Matulonis, Ursula; Berlin, Suzanne; Whalen, Christin; Obermayer, Elizabeth; Liu, Joyce; Campos, Susana] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Lee, Hang] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Penson, Richard; Krasner, Carolyn] Massachusetts Gen Hosp, Hematol & Oncol, Boston, MA 02114 USA. [Horowitz, Neil] Brigham & Womens Hosp, Div Gynecol Oncol, Boston, MA 02115 USA. RP Matulonis, U (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM ursula_matulonis@dfci.harvard.edu FU Merck FX Dr. Matulonis received research funding from Merck for the conduct of this study. NR 26 TC 10 Z9 11 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 EI 1432-0843 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD AUG PY 2015 VL 76 IS 2 BP 417 EP 423 DI 10.1007/s00280-015-2813-9 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA CN6ZA UT WOS:000358581900021 PM 26119093 ER PT J AU Donaldson, CW Baker, JN Narayan, RL Provias, TS Rassi, AN Giri, JS Sakhuja, R Weinberg, I Jaff, MR Rosenfield, K AF Donaldson, Cameron W. Baker, Joshua N. Narayan, Rajeev L. Provias, Tim S. Rassi, Andrew N. Giri, Jay S. Sakhuja, Rahul Weinberg, Ido Jaff, Michael R. Rosenfield, Kenneth TI Thrombectomy using suction filtration and veno-venous bypass: Single center experience with a novel device SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE pulmonary embolism; deep venous thrombosis; peripheral venous catheterization; thrombectomy ID THROMBOEMBOLIC PULMONARY-HYPERTENSION; RIGHT HEART THROMBI; ASPIRATION SYSTEM; MANAGEMENT; EMBOLISM; EXTRACTION AB ObjectivesTo describe the first single center experience with a novel aspiration thrombectomy device. BackgroundThe appearance of inferior vena cava or right-sided intracardiac thrombus may prompt consideration of percutaneous thrombectomy as a method to prevent new or worsening pulmonary embolism (PE). The AngioVac is a novel thrombectomy device composed of a cannula and extracorporeal circuit with filter for pump-assisted removal of intravascular debris which is coupled with a reinfusion catheter for return of blood to the patient. The device has been approved by the United States Food and Drug Administration since 2009. This report represents the first significant case series describing its use, feasibility and outcomes in evacuating large caval thrombi or intracardiac masses in PE. MethodsThis is a retrospective analysis of patient and case characteristics and in-hospital clinical outcomes of AngioVac thrombectomy in 14 consecutive patients treated between April 2010 and July 2013 at our institution. ResultsFourteen consecutive patients (mean age 50, 64% female) underwent 15 AngioVac procedures over 40 months. Indications included intracardiac mass (73%), acute PE (33%), and caval thrombus (73%). Four patients (27%) were in shock at the start of the procedure. Peri-procedure mortality was 0% and in-hospital mortality was 13% at a mean follow-up of 23 days. There were no pulmonary hemorrhages, strokes or myocardial infarctions. Though 73% had a post procedural drop in hematocrit, only two bleeding events were related to access site and required a transfusion. ConclusionsAngioVac thrombectomy is feasible in critically ill patients with acute DVT or PE and large caval thrombi or intracardiac masses. (c) 2015 Wiley Periodicals, Inc. C1 [Donaldson, Cameron W.; Narayan, Rajeev L.; Provias, Tim S.; Rassi, Andrew N.; Weinberg, Ido; Jaff, Michael R.; Rosenfield, Kenneth] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Baker, Joshua N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiac Surg, Boston, MA USA. [Giri, Jay S.] Hosp Univ Penn, Div Cardiovasc Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Sakhuja, Rahul] Wellmont CVA Heart Inst, Cardiovasc Med Intervent & Struct Heart Dis, Kingsport, TN USA. RP Rosenfield, K (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,GRB 852K, Boston, MA 02114 USA. EM krosenfield1@mgh.harvard.edu NR 15 TC 21 Z9 21 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 EI 1522-726X J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD AUG PY 2015 VL 86 IS 2 BP E81 EP E87 DI 10.1002/ccd.25583 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CN5TN UT WOS:000358493700008 PM 24975395 ER PT J AU Lexmond, WS Hu, L Pardo, M Heinz, N Rooney, K LaRosa, J Dehlink, E Fiebiger, E Nurko, S AF Lexmond, W. S. Hu, L. Pardo, M. Heinz, N. Rooney, K. LaRosa, J. Dehlink, E. Fiebiger, E. Nurko, S. TI Accuracy of digital mRNA profiling of oesophageal biopsies as a novel diagnostic approach to eosinophilic oesophagitis SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Article DE eosinophilic esophagitis; mRNA; diagnosis; children ID GENE-EXPRESSION AB BackgroundQuantification of tissue eosinophils remains the golden standard in diagnosing eosinophilic oesophagitis (EoE), but this approach suffers from poor specificity. It has been recognized that histopathological changes that occur in patients with EoE are associated with a disease-specific tissue transcriptome. ObjectiveWe hypothesized that digital mRNA profiling targeted at a set of EoE-specific and Th2 inflammatory genes in oesophageal biopsies could help differentiate patients with EoE from those with reflux oesophagitis (RE) or normal tissue histology (NH). MethodsThe mRNA expression levels of 79 target genes were defined in both proximal and distal biopsies of 196 patients with nCounter (R) (Nanostring) technology. According to clinicopathological diagnosis, these patients were grouped in a training set (35 EoE, 30 RE, 30 NH) for building of a three-class prediction model using the random forest method, and a blinded predictive set (n=47) for model validation. ResultsA diagnostic model built on ten differentially expressed genes was able to differentiate with 100% sensitivity and specificity between conditions in the training set. In a blinded predictive set, this model was able to correctly predict EoE in 14 of 18 patients in distal (sensitivity 78%, 95% CI 52-93%) and 16 of 18 patients in proximal biopsies (sensitivity 89%, 95% CI 64-98%), without false-positive diagnosis of EoE in RE or NH patients (specificity 100%, 95% CI 85-100%). Sensitivity was increased to 94% (95% CI 71-100%) when either the best predictive distal or proximal biopsy was used. Conclusion and Clinical RelevanceWe conclude that mRNA profiling of oesophageal tissue is an accurate diagnostic strategy in detecting EoE. C1 [Lexmond, W. S.; Pardo, M.; Heinz, N.; Rooney, K.; LaRosa, J.; Dehlink, E.; Fiebiger, E.; Nurko, S.] Harvard Univ, Sch Med, Boston Childrens Hosp,Eosinophil Gastrointestinal, Div Gastroenterol & Nutr,Ctr Motil & Funct Gastro, Boston, MA USA. [Hu, L.] Dana Farber Canc Inst, Ctr Canc Computat Biol, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Nurko, S (reprint author), 300 Longwood Ave, Boston, MA 02115 USA. EM samuel.nurko@childrens.harvard.edu FU Gerber Foundation; National Institutes of Health (NIH) [R01AI075037, K24DK82792-1]; Research Council, Boston Children's Hospital; Mead Johnson Nutrition Co.; Royal Netherlands Academy of Arts and Sciences; Banning de Jong Fund in The Netherlands; Austrian Academy of Sciences; Harvard Digestive Diseases Center [P30 DK034854] FX This work was supported by the Gerber Foundation (to E.F. and S.N.). Further support came from National Institutes of Health (NIH) Grants R01AI075037 (to E.F.) and K24DK82792-1 (to S.N.) and the Research Council, Boston Children's Hospital (pilot study, to S.N and E.F.). This study was further supported by an unrestricted gift from Mead Johnson Nutrition Co. to the Division of Gastroenterology and Nutrition (Wayne I. Lencer), E.F., and W.L. (unrestricted postdoctoral research fellowship). W.L. is further supported by grants from the Ter Meulen Fund of the Royal Netherlands Academy of Arts and Sciences and the Banning de Jong Fund in The Netherlands. E.D. was funded by the APART Program of the Austrian Academy of Sciences. This work was also supported by the Harvard Digestive Diseases Center Grant P30 DK034854. NR 22 TC 4 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0954-7894 EI 1365-2222 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD AUG PY 2015 VL 45 IS 8 BP 1317 EP 1327 DI 10.1111/cea.12523 PG 11 WC Allergy; Immunology SC Allergy; Immunology GA CN5DV UT WOS:000358450900005 PM 25728460 ER PT J AU Hicks, JK Bishop, JR Sangkuhl, K Muller, DJ Ji, Y Leckband, SG Leeder, JS Graham, RL Chiulli, DL LLerena, A Skaar, TC Scott, SA Stingl, JC Klein, TE Caudle, KE Gaedigk, A AF Hicks, J. K. Bishop, J. R. Sangkuhl, K. Mueller, D. J. Ji, Y. Leckband, S. G. Leeder, J. S. Graham, R. L. Chiulli, D. L. LLerena, A. Skaar, T. C. Scott, S. A. Stingl, J. C. Klein, T. E. Caudle, K. E. Gaedigk, A. TI Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID PLASMA-CONCENTRATIONS; PSYCHIATRIC-PATIENTS; ANTIDEPRESSANT TREATMENT; PERSONALIZED MEDICINE; SERUM CONCENTRATIONS; GENETIC-VARIABILITY; PAROXETINE; UPDATE; POLYMORPHISMS; METABOLISM AB Selective serotonin reuptake inhibitors (SSRIs) are primary treatment options for major depressive and anxiety disorders. CYP2D6 and CYP2C19 polymorphisms can influence the metabolism of SSRIs, thereby affecting drug efficacy and safety. We summarize evidence from the published literature supporting these associations and provide dosing recommendations for fluvoxamine, paroxetine, citalopram, escitalopram, and sertraline based on CYP2D6 and/or CYP2C19 genotype (updates at www.pharmgkb.org). C1 [Hicks, J. K.] Cleveland Clin, Dept Pharm, Cleveland, OH 44106 USA. [Hicks, J. K.] Cleveland Clin, Genom Med Inst, Cleveland, OH 44106 USA. [Hicks, J. K.] Case Western Reserve Univ, Lerner Coll Med, Cleveland Clin, Dept Med, Cleveland, OH 44106 USA. [Bishop, J. R.] Univ Minnesota, Coll Pharm, Dept Expt & Clin Pharmacol, Minneapolis, MN 55455 USA. [Sangkuhl, K.; Klein, T. E.] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Mueller, D. J.] Ctr Addict & Mental Hlth, Campbell Family Mental Hlth Res Inst, Toronto, ON, Canada. [Mueller, D. J.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [Ji, Y.] Mayo Clin, Div Lab Genet, Dept Lab Med & Pathol, Rochester, MN USA. [Leckband, S. G.] Univ Calif San Diego, Vet Affairs San Diego Healthcare Syst, Mental Hlth Care Line, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92103 USA. [Leckband, S. G.] Dept Psychiat, San Diego, CA USA. [Leeder, J. S.; Gaedigk, A.] Childrens Mercy Hosp, Div Clin Pharmacol Toxicol & Innovat Therapeut, Kansas City, MO 64108 USA. [Leeder, J. S.; Gaedigk, A.] Univ Missouri, Dept Pediat, Kansas City, MO 64110 USA. [Graham, R. L.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Chiulli, D. L.] Vet Affairs Palo Alto Hlth Care Syst, San Jose Div, San Jose, CA USA. [LLerena, A.] Extremadura Univ Hosp, CICAB Clin Res Ctr, Badajoz, Spain. [LLerena, A.] Sch Med, Badajoz, Spain. [Skaar, T. C.] Indiana Univ Sch Med, Dept Med, Div Clin Pharmacol, Indianapolis, IN 46202 USA. [Scott, S. A.] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Stingl, J. C.] Fed Inst Drugs & Med Devices, Bonn, Germany. [Caudle, K. E.] St Jude Childrens Res Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA. RP Gaedigk, A (reprint author), Childrens Mercy Hosp, Div Clin Pharmacol Toxicol & Innovat Therapeut, Kansas City, MO 64108 USA. EM agaedigk@cmh.edu RI Bishop, Jeffrey/K-6559-2015; Mueller, Daniel/L-4159-2016; OI Bishop, Jeffrey/0000-0001-7653-8980; Mueller, Daniel/0000-0003-4978-4400; Llerena, Addrian/0000-0002-2602-1569; LLerena, Adrian/0000-0002-5663-7081 FU National Institutes of Health/National Institute of General Medical Science (NIH/NIGMS); PAAR4Kids [U01 GM92666]; PharmGKB [R24 GM61374]; NIH [K08MH083888, K23GM104401, 2R01GM088076]; [U01 HL0105198] FX We acknowledge the critical input of members of the Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network, funded by the National Institutes of Health/National Institute of General Medical Science (NIH/NIGMS), PAAR4Kids (U01 GM92666), PharmGKB (R24 GM61374), and U01 HL0105198. We acknowledge the critical input of Dr. Mary V. Relling (St Jude Children's Research Hospital), Houda Hachad (Translational Software), and Andria L. Del Tredici (Millennium Health). This work is also funded by NIH grants K08MH083888 (to JRB), K23GM104401 (to SAS), and 2R01GM088076 (to TCS/AG). On behalf of CPIC, the authors are dedicating this guideline to the late David A. Mrazek, MD, a pioneer and advocate of psychiatric pharmacogenetics. NR 36 TC 60 Z9 61 U1 7 U2 27 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD AUG PY 2015 VL 98 IS 2 BP 127 EP 134 DI 10.1002/cpt.147 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CN5WN UT WOS:000358503400005 PM 25974703 ER PT J AU Srinivasan, S Florez, JC AF Srinivasan, S. Florez, J. C. TI Therapeutic Challenges in Diabetes Prevention: We Have Not Found the "Exercise Pill" SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Review ID IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE INTERVENTION; CARDIOVASCULAR EVENTS; OBESE SUBJECTS; METFORMIN; PROGRAM; INSULIN; TRIAL; RISK; ROSIGLITAZONE AB Type 2 diabetes has become an enormous public health burden, making diabetes prevention a pressing issue. While lifestyle modification is the most effective preventive strategy, it is resource-intensive and not universally sustainable. We review the evidence on pharmacological options for diabetes prevention, in search of a medication that is efficacious, easy to adhere to, well tolerated, and cost-effective. With the exception of metformin, most other drugs have either limited efficacy or costly side effects. C1 [Srinivasan, S.] Massachusetts Gen Hosp, Dept Pediat, Pediat Endocrine Unit, Boston, MA 02114 USA. [Srinivasan, S.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Srinivasan, S.; Florez, J. C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, J. C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Florez, J. C.] Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Srinivasan, S.; Florez, J. C.] Broad Inst Harvard Massachusetts Inst Technol, Program Med & Populat Genet, Cambridge, MA USA. RP Florez, JC (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM jcflorez@partners.org FU NIH training grant [T32-GM007748] FX SS is supported by NIH training grant T32-GM007748. We thank Ayesha Muhammad for her help with Figure 1 as well as the other members of the Florez lab for helpful discussion and feedback. NR 36 TC 9 Z9 9 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD AUG PY 2015 VL 98 IS 2 BP 162 EP 169 DI 10.1002/cpt.146 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CN5WN UT WOS:000358503400008 PM 25974616 ER PT J AU Nieves, CI Kaida, A Seage, GR Kabakyenga, J Muyindike, W Boum, Y Mocello, AR Martin, JN Hunt, PW Haberer, JE Bangsbereg, DR Mafthews, LT AF Nieves, Christina I. Kaida, Angela Seage, George R., III Kabakyenga, Jerome Muyindike, Winnie Boum, Yap Mocello, A. Rain Martin, Jeffrey N. Hunt, Peter W. Haberer, Jessica E. Bangsbereg, David R. Mafthews, Lynn T. TI The influence of partnership on contraceptive use among HIV-infected women accessing antiretroviral therapy in rural Uganda SO CONTRACEPTION LA English DT Article DE HIV; Antiretroviral therapy; Family planning; Contraceptive use; Uganda ID PROSPECTIVE COHORT; EXPANDING ACCESS; AFFECTED COUPLES; POSITIVE WOMEN; SOUTH-AFRICA; MEN; PREGNANCIES; INTENTIONS; PROJECT; RISK AB Objective: The objective was to determine individual and dyadic factors associated with effective contraceptive use among human immunodeficiency virus (HIV)-infected women accessing antiretroviral therapy (ART) in rural Uganda. Study design: HIV-infected women enrolled in the Uganda AIDS Rural Treatment Outcomes cohort completed questionnaires (detailing sociobehavioral characteristics, sexual and reproductive history, contraceptive use, fertility desires) and phlebotomy (October 2011 March 2013). We describe prevalence of effective contraceptive use (i.e., consistent condom use and/or oral contraceptives, injectable hormonal contraception, intrauterine device, female sterilization) in the previous 6 months among sexually active, nonpregnant women (18-40 years). We assessed covariates of contraceptive use using multivariable logistic regression. Results: A total of 362 women (median values: age 30 years, CD4 count 397 cells/mm(3), 4.0 years since ART initiation) were included. Among 284 sexually active women, 50% did not desire a(nother) child, and 51% had a seroconcordant partner. Forty-five percent (n=127) reported effective contraceptive use, of whom 57% (n=72) used condoms, 42% (n=53) injectables, 12% (n=15) oral contraceptives and 11% (n=14) other effective methods. Dual contraception was reported by 6% (n=8). Only "partnership fertility desire" was independently associated with contraceptive use; women who reported that neither partner desired a child had significantly increased odds of contraceptive use (adjusted odds ratio: 2.40, 95% confidence interval: 1.07-5.35) compared with women in partnerships where at least one partner desired a child. Conclusions: Less than half of sexually active HIV-infected women accessing ART used effective contraception, of which 44% (n=56) relied exclusively on male condoms, highlighting a continued need to expand access to a wider range of longer-acting female-controlled contraceptive methods. Association with partnership fertility desire underscores the need to include men in reproductive health programming. (C) 2015 Elsevier Inc. All rights reserved. C1 [Nieves, Christina I.; Seage, George R., III] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Kaida, Angela] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. [Kabakyenga, Jerome; Muyindike, Winnie; Boum, Yap; Bangsbereg, David R.] Mbarara Univ Sci & Technol MUST, Mbarara, Uganda. [Boum, Yap] Epictr Mbarara, Mbarara, Uganda. [Mocello, A. Rain; Martin, Jeffrey N.; Hunt, Peter W.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Haberer, Jessica E.; Bangsbereg, David R.; Mafthews, Lynn T.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Haberer, Jessica E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Bangsbereg, David R.; Mafthews, Lynn T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Mafthews, LT (reprint author), MGH Ctr Global Hlth, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM ltmatthews@partners.org FU U.S. National Institutes of Health [R21HD069194, R01MH054907, P30AI027763, U01CA066529, K23 MH095655, K24 MH87227, R01MH087328]; Sullivan Family Foundation; National Institute of General Medical Sciences [U54GM088558] FX The authors would like to thank UARTO study participants and our research team for their contributions to this study. This study was funded by U.S. National Institutes of Health R21HD069194, R01MH054907, P30AI027763, U01CA066529, K23 MH095655, K24 MH87227 and R01MH087328, and the Sullivan Family Foundation. The project was also supported by U54GM088558 from the National Institute of General Medical Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Sciences or the National Institutes of Health. NR 34 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 0010-7824 EI 1879-0518 J9 CONTRACEPTION JI Contraception PD AUG PY 2015 VL 92 IS 2 BP 152 EP 159 DI 10.1016/j.contraception.2015.04.011 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CN6PX UT WOS:000358557800013 PM 25983013 ER PT J AU Ghatalia, P Je, Y Nguyen, PL Trinh, QD Choueiri, TK Sonpavde, G AF Ghatalia, Pooja Je, Youjin Nguyen, Paul L. Quoc-Dien Trinh Choueiri, Toni K. Sonpavde, Guru TI Fatigue with vascular endothelial growth factor receptor tyrosine kinase inhibitors and mammalian target of rapamycin inhibitors in patients with renal cell carcinoma (RCC) and other malignancies: A meta-analysis of randomized clinical trials SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE Vascular endothelial growth factor receptor; Tyrosine kinase inhibitors; Mammalian target of rapamycin inhibitors; Fatigue; Meta-analysis ID CANCER-RELATED FATIGUE; PHASE-III TRIAL; ADVANCED HEPATOCELLULAR-CARCINOMA; PANCREATIC NEUROENDOCRINE TUMORS; DIFFERENTIATED THYROID-CANCER; ADVANCED GASTRIC-CANCER; DOUBLE-BLIND; SORAFENIB; SUNITINIB; EFFICACY AB A trial-level meta-analysis of randomized phase II/III controlled trials in renal cell carcinoma (RCC) and other malignancies was conducted to systematically determine the relative risk (RR) of fatigue, a common side effect associated with single agent therapy with vascular endothelial growth factor receptor (VEGFR) tyrosine Kinase inhibitors (TKI) and mammalian target of rapamycin inhibitors (mTORi). The RR of all grade fatigue and high grade fatigue in 7304 patients from 19 trials was 1.35 (95% CI 1.22-1.49, p < 0.001) and 1.33 (95% CI 0.97-1.82, p = 0.08), respectively in patients receiving VEGFR TKIs or mTORi. The summary incidence of all grade and high grade fatigue in the drug arm was 38.2% (95% CI 31.8-45.1) and 4.0% (95% CI 2.8-5.7), respectively. The type of drug (VEGFR TKI vs. mTORi), line of therapy, age, type of tumor (RCC vs. others) and median duration of therapy did not affect the risk of all-grade fatigue. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Ghatalia, Pooja] Univ Alabama Birmingham UAB, Dept Internal Med, Birmingham, AL USA. [Je, Youjin] Kyung Hee Univ, Dept Food & Nutr, Seoul, South Korea. [Nguyen, Paul L.; Quoc-Dien Trinh; Choueiri, Toni K.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Nguyen, Paul L.; Quoc-Dien Trinh; Choueiri, Toni K.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Sonpavde, Guru] UAB Med Ctr, Dept Internal Med, Sect Med Oncol, Birmingham, AL USA. RP Sonpavde, G (reprint author), UAB Comprehens Canc Ctr, 1802 6th Ave S,NP2540B, Birmingham, AL 35294 USA. EM toni_choueiri@dfci.harvard.edu; gsonpavde@uabmc.edu FU Loker Pinard and Michael Brigham Funds for Kidney Cancer Research; Onyx; Bayer; Trust family FX Dr Choueiri is supported in part by the Trust family, Loker Pinard and Michael Brigham Funds for Kidney Cancer Research for Dr. Choueiri at Dana-Farber Cancer Institute.; Dr Sonpavde receives research support from Onyx and Bayer. NR 52 TC 1 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 EI 1879-0461 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD AUG PY 2015 VL 95 IS 2 BP 251 EP 263 DI 10.1016/j.critrevonc.2015.03.006 PG 13 WC Oncology; Hematology SC Oncology; Hematology GA CN5KL UT WOS:000358468100010 PM 25900071 ER PT J AU Puts, CF Berendsen, TA Bruinsma, BG Ozer, S Luitje, M Usta, OB Yarmush, ML Uygun, K AF Puts, C. F. Berendsen, T. A. Bruinsma, B. G. Ozer, Sinan Luitje, Martha Usta, O. Berk Yarmush, M. L. Uygun, K. TI Polyethylene glycol protects primary hepatocytes during supercooling preservation SO CRYOBIOLOGY LA English DT Article DE Hepatocytes; Preservation; Supercooling; University of Wisconsin solution; Lipid peroxidation; Polyethylene glycol ID COLLAGEN SANDWICH; COLD; TRANSPLANTATION; PEROXIDATION; MEMBRANES; SURVIVAL; BEHAVIOR; RAT AB Cold storage (at 4 degrees C) offers a compromise between the benefits and disadvantages of cooling. It allows storage of organs or cells for later use that would otherwise quickly succumb to warm ischemia, but comprises cold ischemia that, when not controlled properly, can result in severe damage as well by both similar and unique mechanisms. We hypothesized that polyethylene glycol (PEG) 35 kDa would ameliorate these injury pathways and improve cold primary hepatocyte preservation. We show that reduction of the storage temperature to below zero by means of supercooling, or subzero non-freezing, together with PEG supplementation increases the viable storage time of primary rat hepatocytes in University of Wisconsin (UW) solution from 1 day to 4 days. We find that the addition of 5% PEG 35 kDa to the storage medium prevents cold-induced lipid peroxidation and maintains hepatocyte viability and functionality during storage. These results suggest that PEG supplementation in combination with supercooling may enable a more optimized cell and organ preservation. (C) 2015 Elsevier Inc. All rights reserved. C1 [Puts, C. F.; Berendsen, T. A.; Bruinsma, B. G.; Ozer, Sinan; Luitje, Martha; Usta, O. Berk; Yarmush, M. L.; Uygun, K.] Massachusetts Gen Hosp, Dept Surg, Ctr Engn Med, Boston, MA 02114 USA. [Puts, C. F.; Berendsen, T. A.; Bruinsma, B. G.; Ozer, Sinan; Luitje, Martha; Usta, O. Berk; Yarmush, M. L.; Uygun, K.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Yarmush, M. L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA. RP Yarmush, ML (reprint author), 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org; uygun.korkut@mgh.harvard.edu FU US National Institutes of Health; Shriners Hospitals for Children FX Statement of funding: This work was supported by the US National Institutes of Health and the Shriners Hospitals for Children. NR 17 TC 2 Z9 2 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0011-2240 EI 1090-2392 J9 CRYOBIOLOGY JI Cryobiology PD AUG PY 2015 VL 71 IS 1 BP 125 EP 129 DI 10.1016/j.cryobiol.2015.04.010 PG 5 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA CN7RW UT WOS:000358632700018 PM 25936340 ER PT J AU Ahmari, SE Dougherty, DD AF Ahmari, Susanne E. Dougherty, Darin D. TI DISSECTING OCD CIRCUITS: FROM ANIMAL MODELS TO TARGETED TREATMENTS SO DEPRESSION AND ANXIETY LA English DT Review DE obsessive-compulsive disorder (OCD); cortico-striato-thalamo-cortical circuits; prefrontal cortex; orbitofrontal cortex (OFC); ventral striatum; basal ganglia; deep brain stimulation (DBS); transcranial magnetic stimulation (TMS); anxiety; optogenetics ID OBSESSIVE-COMPULSIVE DISORDER; DEEP BRAIN-STIMULATION; TRANSPORTER GENE SLC1A1; FAMILY-BASED ASSOCIATION; POSITRON-EMISSION-TOMOGRAPHY; BASAL GANGLIA CIRCUITRY; GENOME-WIDE ASSOCIATION; THALAMO-CORTICAL LOOP; QUALITY-OF-LIFE; SYMPTOM PROVOCATION AB Obsessive-compulsive disorder (OCD) is a chronic, severe mental illness with up to 2-3% prevalence worldwide. In fact, OCD has been classified as one of the world's 10 leading causes of illness-related disability according to the World Health Organization, largely because of the chronic nature of disabling symptoms.([1]) Despite the severity and high prevalence of this chronic and disabling disorder, there is still relatively limited understanding of its pathophysiology. However, this is now rapidly changing due to development of powerful technologies that can be used to dissect the neural circuits underlying pathologic behaviors. In this article, we describe recent technical advances that have allowed neuroscientists to start identifying the circuits underlying complex repetitive behaviors using animal model systems. In addition, we review current surgical and stimulation-based treatments for OCD that target circuit dysfunction. Finally, we discuss how findings from animal models may be applied in the clinical arena to help inform and refine targeted brain stimulation-based treatment approaches. C1 [Ahmari, Susanne E.] Univ Pittsburgh, Dept Psychiat, Translat Neurosci Program, Pittsburgh, PA 15219 USA. [Dougherty, Darin D.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Ahmari, SE (reprint author), Univ Pittsburgh, Dept Psychiat, Room 227,450 Technol Dr, Pittsburgh, PA 15219 USA. EM ahmarise@upmc.edu FU NIMH [K08MH087718, R21 MH096200, R01MH104255, R01 MH091078]; NARSAD Young Investigator Award; Burroughs Wellcome CAMS Award; MQ Fellows Award; DARPA [W911NF-14-2-0045]; NIH/NCCAM [R01 AT006364-01A1]; NIH [P50MH086400, 7R01MH068376-07, U01 MH0766179-05]; NIH/NIA [2R01AG013241]; Medtronic RECLAIM; Genentech, Inc. FX Contract grant sponsor: NIMH; Contract grant numbers: K08MH087718, R21 MH096200, R01MH104255, and R01 MH091078; Contract grant sponsor: NARSAD Young Investigator Award; Contract grant sponsor: Burroughs Wellcome CAMS Award; Contract grant sponsor: MQ Fellows Award; Contract grant sponsor: DARPA; Contract grant number: W911NF-14-2-0045; Contract grant sponsor: NIH/NCCAM; Contract grant number: R01 AT006364-01A1; Contract grant sponsor: NIH; Contract grant numbers: P50MH086400, 7R01MH068376-07, and U01 MH0766179-05; Contract grant sponsor: NIH/NIA; Contract grant number: 2R01AG013241; Contract grant sponsor: Medtronic RECLAIM; Contract grant sponsor: Genentech, Inc. NR 141 TC 11 Z9 11 U1 8 U2 25 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 2015 VL 32 IS 8 BP 550 EP 562 DI 10.1002/da.22367 PG 13 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA CN7NS UT WOS:000358621900002 PM 25952989 ER PT J AU Goldberg, JF Freeman, MP Balon, R Citrome, L Thase, ME Kane, JM Fava, M AF Goldberg, Joseph F. Freeman, Marlene P. Balon, Richard Citrome, Leslie Thase, Michael E. Kane, John M. Fava, Maurizio TI THE AMERICAN SOCIETY OF CLINICAL PSYCHOPHARMACOLOGY SURVEY OF PSYCHOPHARMACOLOGISTS' PRACTICE PATTERNS FOR THE TREATMENT OF MOOD DISORDERS SO DEPRESSION AND ANXIETY LA English DT Article DE depression; antidepressant; mood stabilizer; antipsychotic; psychopharmacology; survey ID MAJOR DEPRESSIVE DISORDER; ASTERISK-D REPORT; SEROTONIN REUPTAKE INHIBITORS; BIPOLAR DEPRESSION; DOUBLE-BLIND; ANTIDEPRESSANT; OUTPATIENTS; MEDICATION; ANXIETY; AUGMENTATION AB BackgroundOptimal successive treatment decisions are not well established after an initial medication nonresponse in major depressive disorder or bipolar disorder. While practice guidelines offer consensus-based expert treatment recommendations, little is known about "real world" pharmacology decision making by practicing psychopharmacologists. Materials and MethodsWe surveyed via Internet the national membership of the American Society of Clinical Psychopharmacology (ASCP) to study preferred pharmacotherapy strategies and factors that influence medication choices for patients with mood disorders. ResultsSurveys were returned by 154/752 ASCP members (21%). After nonresponse to a serotonin reuptake inhibitor in major depressive disorder, participants equally favored switching within or across antidepressant classes. After a partial response, adjunctive bupropion was the preferred intervention, followed by changing antidepressant classes. Atypical antipsychotic augmentation was only a fourth-line consideration, even though moderate or marked efficacy was perceived in most instances with olanzapine, aripiprazole, and quetiapine. Respondents favored avoiding antidepressants in bipolar I patients with mixed/cycling features or prior antidepressant-associated mania/hypomania. In rapid cyclers, they advocated antidepressant cessation and preferred the use of atypical antipsychotics and lamotrigine. ConclusionsParticipating psychopharmacologists treating adults with mood disorders report prescribing medications that largely mirror the evidence base with only a few notable exceptions, in consideration of the characteristics of definable clinical subpopulations. C1 [Goldberg, Joseph F.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Freeman, Marlene P.; Fava, Maurizio] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Freeman, Marlene P.; Fava, Maurizio] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Balon, Richard] Wayne State Univ, Dept Psychiat & Behav Neurosci, Detroit, MI 48207 USA. [Balon, Richard] Wayne State Univ, Dept Anesthesiol, Detroit, MI USA. [Citrome, Leslie] New York Med Coll, Dept Psychiat & Behav Sci, Valhalla, NY 10595 USA. [Thase, Michael E.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Dept Psychiat, Philadelphia, PA USA. [Kane, John M.] Zucker Hillside Hosp North Shore Long Isl Jewish, Dept Psychiat, Glen Oaks, NY USA. [Kane, John M.] Hofstra North Shore Long Isl Jewish Sch Med, Dept Psychiat, Uniondale, NY USA. [Kane, John M.] North Shore Long Isl Jewish Hlth Syst, Behav Hlth Serv, New Hyde Pk, NY USA. RP Goldberg, JF (reprint author), 128 East Ave, Norwalk, CT 06851 USA. EM joseph.goldberg@mssm.edu OI Citrome, Leslie/0000-0002-6098-9266 NR 44 TC 6 Z9 6 U1 0 U2 7 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 2015 VL 32 IS 8 BP 605 EP 613 DI 10.1002/da.22378 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA CN7NS UT WOS:000358621900007 PM 26129956 ER PT J AU Dashti, HS Follis, JL Smith, CE Tanaka, T Garaulet, M Gottlieb, DJ Hruby, A Jacques, PF Kiefte-de Jong, JC Lamon-Fava, S Scheer, FAJL Bartz, TM Kovanen, L Wojczynski, MK Frazier-Wood, AC Ahluwalia, TS Perala, MM Jonsson, A Muka, T Kalafati, IP Mikkila, V Ordovas, JM AF Dashti, Hassan S. Follis, Jack L. Smith, Caren E. Tanaka, Toshiko Garaulet, Marta Gottlieb, Daniel J. Hruby, Adela Jacques, Paul F. Kiefte-de Jong, Jessica C. Lamon-Fava, Stefania Scheer, Frank A. J. L. Bartz, Traci M. Kovanen, Leena Wojczynski, Mary K. Frazier-Wood, Alexis C. Ahluwalia, Tarunveer S. Perala, Mia-Maria Jonsson, Anna Muka, Taulant Kalafati, Ioanna P. Mikkila, Vera Ordovas, Jose M. CA CHARGE Nutr Study Grp TI Gene-Environment Interactions of Circadian-Related Genes for Cardiometabolic Traits SO DIABETES CARE LA English DT Article ID FASTING PLASMA-GLUCOSE; TYPE-2 DIABETES RISK; METABOLIC SYNDROME; INSULIN-RESISTANCE; SLEEP DURATION; NORTH-AMERICAN; CLOCK; VARIANTS; OBESITY; ASSOCIATION AB OBJECTIVE Common circadian-related gene variants associate with increased risk for metabolic alterations including type 2 diabetes. However, little is known about whether diet and sleep could modify associations between circadian-related variants (CLOCK-rs1801260, CRY2-rs11605924, MTNR1B-rs1387153, MTNR1B-rs10830963, NR1D1-rs2314339) and cardiometabolic traits (fasting glucose [FG], HOMA-insulin resistance, BMI, waist circumference, and HDL-cholesterol) to facilitate personalized recommendations. RESEARCH DESIGN AND METHODS We conducted inverse-variance weighted, fixed-effect meta-analyses of results of adjusted associations and interactions between dietary intake/sleep duration and selected variants on cardiometabolic traits from 15 cohort studies including up to 28,190 participants of European descent from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. RESULTS We observed significant associations between relative macronutrient intakes and glycemic traits and short sleep duration (<7 h) and higher FG and replicated known MTNR1B associations with glycemic traits. No interactions were evident after accounting for multiple comparisons. However, we observed nominally significant interactions (all P < 0.01) between carbohydrate intake and MTNR1B-rs1387153 for FG with a 0.003 mmol/L higher FG with each additional 1% carbohydrate intake in the presence of the T allele, between sleep duration and CRY2-rs11605924 for HDL-cholesterol with a 0.010 mmol/L higher HDL-cholesterol with each additional hour of sleep in the presence of the A allele, and between long sleep duration (>= 9 h) and MTNR1B-rs1387153 for BMI with a 0.60 kg/m(2) higher BMI with long sleep duration in the presence of the T allele relative to normal sleep duration (>= 7 to < 9 h). CONCLUSIONS Our results suggest that lower carbohydrate intake and normal sleep duration may ameliorate cardiometabolic abnormalities conferred by common circadian-related genetic variants. Until further mechanistic examination of the nominally significant interactions is conducted, recommendations applicable to the general population regarding diet-specifically higher carbohydrate and lower fat composition-and normal sleep duration should continue to be emphasized among individuals with the investigated circadian-related gene variants. C1 [Dashti, Hassan S.; Smith, Caren E.; Ordovas, Jose M.] Tufts Univ, Nutr & Genom Lab, Human Nutr Res Ctr, Jean Mayer US Dept Agr, Boston, MA 02111 USA. [Follis, Jack L.] Univ St Thomas, Dept Math Comp Sci & Cooperat Engn, Houston, TX 77006 USA. [Tanaka, Toshiko] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA. [Garaulet, Marta] Univ Murcia, Dept Physiol, Murcia, Spain. [Gottlieb, Daniel J.; Scheer, Frank A. J. L.] Brigham & Womens Hosp, Div Sleep & Circadian Disorders, Boston, MA 02115 USA. [Gottlieb, Daniel J.; Scheer, Frank A. J. L.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. [Gottlieb, Daniel J.] VA Boston Healthcare Syst, Sleep Disorders Ctr, Boston, MA USA. [Hruby, Adela] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Jacques, Paul F.] Tufts Univ, Nutr Epidemiol Lab, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Kiefte-de Jong, Jessica C.; Muka, Taulant] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Kiefte-de Jong, Jessica C.] Leiden Univ Coll, Global Publ Hlth, The Hague, Netherlands. [Lamon-Fava, Stefania] Tufts Univ, Cardiovasc Nutr Lab, Human Nutr Res Ctr, Jean Mayer US Dept Agr, Boston, MA 02111 USA. [Bartz, Traci M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Bartz, Traci M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Kovanen, Leena] Natl Inst Hlth & Welf THL, Dept Mental Hlth & Subst Abuse Serv, Helsinki, Finland. [Wojczynski, Mary K.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [Frazier-Wood, Alexis C.] ARS, USDA, Childrens Nutr Res Ctr, Dept Pediat,Baylor Coll Med, Houston, TX USA. [Ahluwalia, Tarunveer S.; Jonsson, Anna] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res,Sect Metab Genet, Copenhagen, Denmark. [Ahluwalia, Tarunveer S.] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen Prospect Studies Asthma Childhood, Copenhagen, Denmark. [Ahluwalia, Tarunveer S.] Gentofte Univ Hosp, Danish Pediat Asthma Ctr, Copenhagen, Denmark. [Perala, Mia-Maria] Natl Inst Hlth & Welf THL, Dept Chron Dis Prevent, Helsinki, Finland. [Kalafati, Ioanna P.] Harokopio Univ, Dept Nutr & Dietet, Athens, Greece. [Mikkila, Vera] Univ Helsinki, Dept Food & Environm Sci, Div Nutr, Helsinki, Finland. [Mikkila, Vera] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Ordovas, Jose M.] Ctr Nacl Invest Cardiovasc CNIC, Dept Epidemiol, Madrid, Spain. [Ordovas, Jose M.] Inst Madrileno Estudios Avanzados Alimentac IMDEA, Madrid, Spain. RP Dashti, HS (reprint author), Tufts Univ, Nutr & Genom Lab, Human Nutr Res Ctr, Jean Mayer US Dept Agr, Boston, MA 02111 USA. EM hassan.dashti@tufts.edu RI Deloukas, Panos/B-2922-2013; OI Deloukas, Panos/0000-0001-9251-070X; Dashti, Hassan S/0000-0002-1650-679X; Kovanen, Leena/0000-0002-3552-124X; Mannisto, Satu/0000-0002-8668-3046; Kiefte-de Jong, Jessica/0000-0002-8136-0918; Jorgensen, Torben/0000-0001-9453-2830; Lahti, Jari/0000-0002-4310-5297; Linneberg, Allan/0000-0002-0994-0184 FU National Heart, Lung, and Blood Institute [HHSN268200800007C]; U.S. Department of Agriculture [58-1950-0-014]; American Heart Association [14BGIA18740011]; Academy of Finland [117787]; Italian Ministry of Health [ICS110.1/RF97.71]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]; National Center for Advancing Translational Sciences [UL1TR000124]; National Institutes of Health [R21-DK-089378, R01-HL-094806]; [K08-HL-112845-01] FX Infrastructure for the CHARGE Consortium is supported in part by the National Heart, Lung, and Blood Institute grant HHSN268200800007C. Support was provided by the U.S. Department of Agriculture, under agreement no. 58-1950-0-014, American Heart Association (grant 14BGIA18740011), Academy of Finland (grant 117787), Italian Ministry of Health (grant ICS110.1/RF97.71), National Institute of Diabetes and Digestive and Kidney Diseases (grant DK063491), National Center for Advancing Translational Sciences (grant UL1TR000124). C.E.S. is supported by K08-HL-112845-01. F.A.J.L.S. was supported in part by National Institutes of Health grants R21-DK-089378 and R01-HL-094806. Cohort-specific sources of support and acknowledgments are presented in Supplementary Table 1. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the U.S. Department of Agriculture. NR 40 TC 8 Z9 8 U1 2 U2 15 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 2015 VL 38 IS 8 BP 1456 EP 1466 DI 10.2337/dc14-2709 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CN8EY UT WOS:000358673200021 PM 26084345 ER PT J AU Cefalu, WT Bray, GA Home, PD Garvey, WT Klein, S Pi-Sunyer, FX Hu, FB Raz, I Van Gaal, L Wolfe, BM Ryan, DH AF Cefalu, William T. Bray, George A. Home, Philip D. Garvey, W. Timothy Klein, Samuel Pi-Sunyer, F. Xavier Hu, Frank B. Raz, Itamar Van Gaal, Luc Wolfe, Bruce M. Ryan, Donna H. TI Advances in the Science, Treatment, and Prevention of the Disease of Obesity: Ref lections From a Diabetes Care Editors' Expert Forum SO DIABETES CARE LA English DT Article ID BODY-MASS INDEX; METABOLICALLY-HEALTHY OBESITY; FATTY LIVER-DISEASE; RANDOMIZED-CONTROLLED-TRIAL; POLYCYSTIC-OVARY-SYNDROME; LIFE-STYLE INTERVENTION; CONTROLLED-RELEASE PHENTERMINE/TOPIRAMATE; TOPIRAMATE EXTENDED-RELEASE; PATIENT-CENTERED APPROACH; OBSTRUCTIVE SLEEP-APNEA AB As obesity rates increase, so too do the risks of type 2 diabetes, cardiovascular disease, and numerous other detrimental conditions. The prevalence of obesity in U.S. adults more than doubled between 1980 and 2010, from 15.0 to 36.1%. Although this trend may be leveling off, obesity and its individual, societal, and economic costs remain of grave concern. In June 2014, a Diabetes Care Editors' Expert Forum convened to review the state of obesity research and discuss the latest prevention initiatives and behavioral, medical, and surgical therapies. This article, an outgrowth of the forum, offers an expansive view of the obesity epidemic, beginning with a discussion of its root causes. Recent insights into the genetic and physiological factors that influence body weight are reviewed, as are the pathophysiology of obesity-related metabolic dysfunction and the concept of metabolically healthy obesity. The authors address the crucial question of how much weight loss is necessary to yield meaningful benefits. They describe the challenges of behavioral modification and predictors of its success. The effects of diabetes pharmacotherapies on body weight are reviewed, including potential weight-neutral combination therapies. The authors also summarize the evidence for safety and efficacy of pharmacotherapeutic and surgical obesity treatments. The article concludes with an impassioned call for researchers, clinicians, governmental agencies, health policymakers, and health-related industries to collectively embrace the urgent mandate to improve prevention and treatment and for society at large to acknowledge and manage obesity as a serious disease. C1 [Cefalu, William T.; Bray, George A.; Ryan, Donna H.] Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70803 USA. [Home, Philip D.] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Garvey, W. Timothy] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. [Garvey, W. Timothy] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Klein, Samuel] Washington Univ, Sch Med, Ctr Human Nutr, St Louis, MO USA. [Pi-Sunyer, F. Xavier] Columbia Univ, Dept Med, Obes Res Ctr, New York, NY USA. [Hu, Frank B.] Harvard Univ, Dept Nutr, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Hu, Frank B.] Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Raz, Itamar] Hadassah Hebrew Univ Hosp, Diabet Unit, Dept Internal Med, Jerusalem, Israel. [Van Gaal, Luc] Univ Antwerp Hosp, Dept Endocrinol Diabetol & Metab, Antwerp, Belgium. [Wolfe, Bruce M.] Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97201 USA. RP Cefalu, WT (reprint author), Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70803 USA. EM william.cefalu@pbrc.edu FU National Institute of General Medical Sciences of the National Institutes of Health [1-U54-GM-104940] FX W.T.C. is supported in part by grant number 1-U54-GM-104940 from the National Institute of General Medical Sciences of the National Institutes of Health. NR 198 TC 16 Z9 17 U1 5 U2 15 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 2015 VL 38 IS 8 BP 1567 EP 1582 DI 10.2337/dc15-1081 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CN8EY UT WOS:000358673200035 PM 26421334 ER PT J AU Toth, DJA Gundlapalli, AV Khader, K Pettey, WBP Rubin, MA Adler, FR Samore, MH AF Toth, Damon J. A. Gundlapalli, Adi V. Khader, Karim Pettey, Warren B. P. Rubin, Michael A. Adler, Frederick R. Samore, Matthew H. TI Estimates of Outbreak Risk from New Introductions of Ebola with Immediate and Delayed Transmission Control SO EMERGING INFECTIOUS DISEASES LA English DT Article ID VIRUS DISEASE; BRANCHING-PROCESSES; SEPTEMBER 2014; DISTRIBUTIONS; IMPORTATION AB While the ongoing Ebola outbreak continues in the West Africa countries of Guinea, Sierra Leone, and Liberia, health officials elsewhere prepare for new introductions of Ebola from infected evacuees or travelers. We analyzed transmission data from patients (i.e., evacuees, international travelers, and those with locally acquired illness) in countries other than the 3 with continuing Ebola epidemics and quantitatively assessed the outbreak risk from new introductions by using different assumptions for transmission control (i.e., immediate and delayed). Results showed that, even in countries that can quickly limit expected number of transmissions per case to <1, the probability that a single introduction will lead to a substantial number of transmissions is not negligible, particularly if transmission variability is high. Identifying incoming infected travelers before symptom onset can decrease worst-case outbreak sizes more than reducing transmissions from patients with locally acquired cases, but performing both actions can have a synergistic effect. C1 [Toth, Damon J. A.] Univ Utah, Sch Med, Dept Internal Med, Div Epidemiol, Salt Lake City, UT 84132 USA. [Toth, Damon J. A.; Gundlapalli, Adi V.; Khader, Karim; Pettey, Warren B. P.; Rubin, Michael A.; Adler, Frederick R.; Samore, Matthew H.] Univ Utah, Salt Lake City, UT 84132 USA. [Toth, Damon J. A.; Gundlapalli, Adi V.; Khader, Karim; Pettey, Warren B. P.; Rubin, Michael A.; Samore, Matthew H.] US Dept Vet Affairs, Salt Lake City Hlth Care Syst, Salt Lake City, UT USA. RP Toth, DJA (reprint author), Univ Utah, Sch Med, Dept Internal Med, Div Epidemiol, 295 Chipeta Way, Salt Lake City, UT 84132 USA. EM Damon.Toth@hsc.utah.edu NR 34 TC 5 Z9 5 U1 4 U2 13 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 EI 1080-6059 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD AUG PY 2015 VL 21 IS 8 BP 1402 EP 1408 DI 10.3201/eid2108.150170 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CN5GR UT WOS:000358458300016 PM 26196264 ER PT J AU Larose, TL Brumpton, BM Langhammer, A Camargo, CA Chen, Y Romundstad, P Mai, XM AF Larose, Tricia L. Brumpton, Ben M. Langhammer, Arnulf Camargo, Carlos A., Jr. Chen, Yue Romundstad, Pal Mai, Xiao-Mei TI Serum 25-hydroxyvitamin D level, smoking and lung function in adults: the HUNT Study SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; VITAMIN-D STATUS; EPITHELIAL-CELLS; PROSPECTIVE COHORT; CIGARETTE-SMOKE; ASSOCIATION; HEALTH; FIBROBLASTS; PROTEIN; ASTHMA AB The association between serum 25-hydroxyvitamin D (25(OH)D) level and lung function changes in the general population remains unclear. We conducted cross-sectional (n= 1220) and follow-up (n= 869) studies to investigate the interrelationship of serum 25(OH)D, smoking and lung function changes in a random sample of adults from the Nord-Trondelag Health (HUNT) Study, Norway. Lung function was measured using spirometry and included forced expiratory volume in 1 s (FEV1) % predicted, forced vital capacity (FVC) % pred and FEV1/FVC ratio. Multiple linear and logistic regression models estimated the adjusted difference in lung function measures or lung function decline, adjusted odds ratios for impaired lung function or development of impaired lung function and 95% confidence intervals. 40% of adults had serum 25(OH)D levels <50 nmol.L-1. Overall, those with a serum 25(OH)D level < 50 nmol.L-1 showed worse lung function and increased odds of impaired lung function compared to the >= 50 nmol.L-1 group. These associations tended to be stronger among ever-smokers, including greater decline in FEV1/FVC ratio and greater odds of the development of impaired lung function (FEV1/FVC < 70% OR 2.4, 95% CI 1.2-4.9). Associations among never-smokers were null. Results from cross-sectional and follow-up studies were consistent. There were no associations between serum 25(OH)D levels and lung function or lung function changes in never-smokers, whereas significant associations were observed in ever-smokers. C1 [Larose, Tricia L.; Brumpton, Ben M.; Romundstad, Pal; Mai, Xiao-Mei] Norwegian Univ Sci & Technol, Fac Med, Dept Publ Hlth & Gen Practice, N-7491 Trondheim, Norway. [Langhammer, Arnulf] Norwegian Univ Sci & Technol, Fac Med, HUNT Res Ctr, Verdal, Norway. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. [Chen, Yue] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON, Canada. RP Larose, TL (reprint author), Norwegian Univ Sci & Technol, Fac Med, Dept Publ Hlth & Gen Practice, N-7491 Trondheim, Norway. EM tricia.larose@ntnu.no FU Research Council of Norway [201895/V50]; ExtraStiftelsen Helse og Rehabilitering and Landsforeningen for hjerte-og lungesyke (the Norwegian Extra Foundation for Health and Rehabilitation and the Norwegian Heart and Lung Patient Organisation) [2011.2.0215]; liason committee of the Central Norway Regional Health Authority - NTNU FX This study was supported by the Research Council of Norway (project 201895/V50), ExtraStiftelsen Helse og Rehabilitering and Landsforeningen for hjerte-og lungesyke (the Norwegian Extra Foundation for Health and Rehabilitation and the Norwegian Heart and Lung Patient Organisation) (project 2011.2.0215) and the liason committee of the Central Norway Regional Health Authority - NTNU. Funding information for this study has been deposited with FundRef. NR 37 TC 1 Z9 1 U1 0 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 2015 VL 46 IS 2 BP 355 EP 363 DI 10.1183/09031936.00226614 PG 9 WC Respiratory System SC Respiratory System GA CN9UQ UT WOS:000358795800012 PM 26022950 ER PT J AU McLaughlin, V Channick, RN Ghofrani, HA Lemarie, JC Naeije, R Packer, M Souza, R Tapson, VF Tolson, J Al Hiti, H Meyer, G Hoeper, MM AF McLaughlin, Vallerie Channick, Richard N. Ghofrani, Hossein-Ardeschir Lemarie, Jean-Christophe Naeije, Robert Packer, Milton Souza, Rogerio Tapson, Victor F. Tolson, Jonathan Al Hiti, Hikmet Meyer, Gisela Hoeper, Marius M. TI Bosentan added to sildenafil therapy in patients with pulmonary arterial hypertension SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article ID COMBINATION; TRIAL AB The safety and efficacy of adding bosentan to sildenafil in pulmonary arterial hypertension (PAH) patients was investigated. In this prospective, double-blind, event-driven trial, symptomatic PAH patients receiving stable sildenafil (>= 20 mg three times daily) for >= 3 months were randomised (1: 1) to placebo or bosentan (125 mg twice daily). The composite primary end-point was the time to the first morbidity/mortality event, defined as all-cause death, hospitalisation for PAH worsening or intravenous prostanoid initiation, atrial septostomy, lung transplant, or PAH worsening. Secondary/exploratory end-points included change in 6-min walk distance and World Health Organization functional class at 16 weeks, change in N-terminal pro-brain natriuretic peptide (NT-proBNP) over time, and all-cause death. Overall, 334 PAH patients were randomised to placebo (n=175) or bosentan (n=159). A primary end-point event occurred in 51.4% of patients randomised to placebo and 42.8% to bosentan (hazard ratio 0.83, 97.31% CI 0.58-1.19; p=0.2508). The mean between-treatment difference in 6-min walk distance at 16 weeks was + 21.8 m (95% CI + 5.9-37.8 m; p=0.0106). Except for NT-proBNP, no difference was observed for any other end-point. The safety profile of bosentan added to sildenafil was consistent with the known bosentan safety profile. In COMPASS-2, adding bosentan to stable sildenafil therapy was not superior to sildenafil monotherapy in delaying the time to the first morbidity/mortality event. C1 [McLaughlin, Vallerie] Univ Michigan Hlth Syst, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. [Channick, Richard N.] Massachusetts Gen Hosp, Pulm & Crit Care, Boston, MA 02114 USA. [Ghofrani, Hossein-Ardeschir] Univ Giessen, D-35390 Giessen, Germany. [Ghofrani, Hossein-Ardeschir] Marburg Lung Ctr, Giessen, Germany. [Lemarie, Jean-Christophe] Effi Stat, Dept Stat, Paris, France. [Naeije, Robert] Erasme Univ Hosp, Dept Cardiol, B-1070 Brussels, Belgium. [Packer, Milton] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. [Souza, Rogerio] Univ Sao Paulo, Sch Med, Inst Heart, Dept Pulm, Sao Paulo, Brazil. [Tapson, Victor F.] Cedars Sinai Med Ctr, Div Pulm & Crit Care Med, Los Angeles, CA 90048 USA. [Tolson, Jonathan] Actelion Pharmaceut Ltd, Global Med Affairs, Allschwil, Switzerland. [Al Hiti, Hikmet] IKEM, Dept Cardiol, Prague, Czech Republic. [Meyer, Gisela] Complexo Hosp Santa Casa De Porto Alegre, Pulm Vasc Res Inst, Porto Alegre, RS, Brazil. [Hoeper, Marius M.] Hannover Med Sch, Dept Resp Med, Hannover, Germany. [Hoeper, Marius M.] German Ctr Lung Res DZL, Hannover, Germany. RP McLaughlin, V (reprint author), Univ Michigan Hlth Syst, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. EM vmclaugh@umich.edu FU Actelion Pharmaceuticals Ltd. FX The COMPASS-2 study was funded by Actelion Pharmaceuticals Ltd. Funding information for this article has been deposited with FundRef. NR 17 TC 36 Z9 36 U1 0 U2 14 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 2015 VL 46 IS 2 BP 405 EP 413 DI 10.1183/13993003.02044-2014 PG 9 WC Respiratory System SC Respiratory System GA CN9UQ UT WOS:000358795800017 PM 26113687 ER PT J AU Protano, MA Xu, H Wang, GQ Polydorides, AD Dawsey, SM Cui, JS Xue, LY Zhang, F Quang, T Pierce, MC Shin, D Schwarz, RA Bhutani, MS Lee, M Parikh, N Hur, C Xu, WR Moshier, E Godbold, J Mitcham, J Hudson, C Richards-Kortum, RR Anandasabapathy, S AF Protano, Marion-Anna Xu, Hong Wang, Guiqi Polydorides, Alexandros D. Dawsey, Sanford M. Cui, Junsheng Xue, Liyan Zhang, Fan Quang, Timothy Pierce, Mark C. Shin, Dongsuk Schwarz, Richard A. Bhutani, Manoop S. Lee, Michelle Parikh, Neil Hur, Chin Xu, Weiran Moshier, Erin Godbold, James Mitcham, Josephine Hudson, Courtney Richards-Kortum, Rebecca R. Anandasabapathy, Sharmila TI Low-Cost High-Resolution Microendoscopy for the Detection of Esophageal Squamous Cell Neoplasia: An International Trial SO GASTROENTEROLOGY LA English DT Article DE Esophageal Neoplasm; Endoscopy; Early Detection of Cancer ID CONFOCAL LASER ENDOMICROSCOPY; RANDOMIZED CONTROLLED-TRIAL; IN-VIVO; BARRETTS-ESOPHAGUS; CARCINOMA; CANCER; CHINA; RISK; EPIDEMIOLOGY; LINXIAN AB BACKGROUND & AIMS: Esophageal squamous cell neoplasia has a high mortality rate as a result of late detection. In high-risk regions such as China, screening is performed by Lugol's chromoendoscopy (LCE). LCE has low specificity, resulting in unnecessary tissue biopsy with a subsequent increase in procedure cost and risk. The purpose of this study was to evaluate the accuracy of a novel, low-cost, high-resolution microendoscope (HRME) as an adjunct to LCE. METHODS: In this prospective trial, 147 consecutive high-risk patients were enrolled from 2 US and 2 Chinese tertiary centers. Three expert and 4 novice endoscopists performed white-light endoscopy followed by LCE and HRME. All optical images were compared with the gold standard of histopathology. RESULTS: By using a per-biopsy analysis, the sensitivity of LCE vs LCE + HRME was 96% vs 91% (P = .0832), specificity was 48% vs 88% (P < .001), positive predictive value was 22% vs 45% (P < .0001), negative predictive value was 98% vs 98% (P = .3551), and overall accuracy was 57% vs 90% (P < .001), respectively. By using a per-patient analysis, the sensitivity of LCE vs LCE + HRME was 100% vs 95% (P = .16), specificity was 29% vs 79% (P < .001), positive predictive value was 32% vs 60%, 100% vs 98%, and accuracy was 47% vs 83% (P < .001). With the use of HRME, 136 biopsies (60%; 95% confidence interval, 53%-66%) could have been spared, and 55 patients (48%; 95% confidence interval, 38%-57%) could have been spared any biopsy. CONCLUSIONS: In this trial, HRME improved the accuracy of LCE for esophageal squamous cell neoplasia screening and surveillance. HRME may be a cost-effective optical biopsy adjunct to LCE, potentially reducing unnecessary biopsies and facilitating real-time decision making in globally underserved regions. ClinicalTrials.gov, NCT 01384708. C1 [Protano, Marion-Anna; Lee, Michelle; Mitcham, Josephine; Hudson, Courtney; Anandasabapathy, Sharmila] Mt Sinai Med Ctr, Div Gastroenterol, New York, NY 10029 USA. [Polydorides, Alexandros D.] Mt Sinai Med Ctr, Dept Pathol, New York, NY 10029 USA. [Moshier, Erin; Godbold, James] Mt Sinai Med Ctr, Dept Preventat Med, New York, NY 10029 USA. [Xu, Hong; Zhang, Fan; Xu, Weiran] Jilin Univ, Dept Endoscopy, Hosp 1, Changchun, Jilin, Peoples R China. [Cui, Junsheng] Jilin Univ, Dept Pathol, Hosp 1, Changchun, Jilin, Peoples R China. [Wang, Guiqi] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Endoscopy, Beijing 100730, Peoples R China. [Xue, Liyan] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Pathol, Beijing 100730, Peoples R China. [Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Quang, Timothy; Shin, Dongsuk; Schwarz, Richard A.; Richards-Kortum, Rebecca R.] Rice Univ, Dept Bioengn, Houston, TX USA. [Pierce, Mark C.] Rutgers State Univ, Biomed Engn, Piscataway, NJ USA. [Bhutani, Manoop S.] Univ Texas MD Anderson Canc Ctr, Dept Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA. [Parikh, Neil] Yale Univ, Div Digest Dis, New Haven, CT USA. [Hur, Chin] Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. [Hur, Chin] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Anandasabapathy, S (reprint author), Baylor Global Initiat, Dept Med & Gastroenterol, One Baylor Plaza, Houston, TX 77030 USA. EM Sharmila.Anandasabapathy@bcm.edu OI Hur, Chin/0000-0002-2819-7576 FU [NCI R21 CA156704] FX Supported by grant NCI R21 CA156704 and ClinicalTrials.gov, NCT 01384708. NR 42 TC 1 Z9 2 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD AUG PY 2015 VL 149 IS 2 BP 321 EP 329 DI 10.1053/j.gastro.2015.04.055 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CN4VX UT WOS:000358429600025 PM 25980753 ER PT J AU Bharucha, AE Batey-Schaefer, B Cleary, PA Murray, JA Cowie, C Lorenzi, G Driscoll, M Harth, J Larkin, M Christofi, M Bayless, M Wimmergren, N Herman, W Whitehouse, F Jones, K Kruger, D Martin, C Ziegler, G Zinsmeister, AR Nathan, DM AF Bharucha, Adil E. Batey-Schaefer, Barbara Cleary, Patricia A. Murray, Joseph A. Cowie, Catherine Lorenzi, Gayle Driscoll, Marsha Harth, Judy Larkin, Mary Christofi, Marielle Bayless, Margaret Wimmergren, Nyra Herman, William Whitehouse, Fred Jones, Kim Kruger, Davida Martin, Cathy Ziegler, Georgia Zinsmeister, Alan R. Nathan, David M. CA Diabet Control Complications TI Delayed Gastric Emptying Is Associated With Early and Long-term Hyperglycemia in Type 1 Diabetes Mellitus SO GASTROENTEROLOGY LA English DT Article DE Diabetic Gastroparesis; HbA1c; Glycemic Control; Neuropathy ID CARDINAL SYMPTOM INDEX; UPPER GASTROINTESTINAL DISORDERS; COMPLICATIONS TRIAL COHORT; ISOTOPE BREATH TEST; GLYCEMIC CONTROL; MICROVASCULAR COMPLICATIONS; FUNCTIONAL DYSPEPSIA; DAILY DIARY; GASTROPARESIS; INTERVENTIONS AB BACKGROUND & AIMS: After the Diabetes Control and Complications Trial (DCCT), the Epidemiology of Diabetes Interventions and Complications (EDIC) study continued to show persistent benefit of prior intensive therapy on neuropathy, retinopathy, and nephropathy in type 1 diabetes mellitus (DM). The relationship between control of glycemia and gastric emptying (GE) is unclear. METHODS: We assessed GE with a C-13-spirulina breath test and symptoms in 78 participants with type 1 diabetes at year 20 of EDIC. The relationship between delayed GE and glycated hemoglobin (HbA1c), complications of DM, and gastrointestinal symptoms were evaluated. RESULTS: GE was normal (37 participants; 50%), delayed (35 participants; 47%), or rapid (2 participants; 3%). The latest mean HbA1c was 7.7%. In univariate analyses, delayed GE was associated with greater DCCT baseline HbA1c and duration of DM before DCCT (P < .04), greater mean HbA1c over an average of 27 years of follow-up evaluation (during DCCT-EDIC, P = .01), lower R-R variability during deep breathing (P = .03) and severe nephropathy (P = .05), and a greater composite upper gastrointestinal symptom score (P < .05). In multivariate models, retinopathy was the only complication of DM associated with delayed GE. Separately, DCCT baseline HbA1c (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1-2.3) and duration of DM (OR, 1.2; 95% CI, 1.01-1.3) before DCCT entry and mean HbA1c during DCCT-EDIC (OR, 2.2; 95% CI, 1.04-4.5) were associated independently with delayed GE. CONCLUSIONS: In the DCCT/EDIC study, delayed GE was remarkably common and associated with gastrointestinal symptoms and with measures of early and long-term hyperglycemia. ClinicalTrials.gov numbers NCT00360815 and NCT00360893. C1 [Bharucha, Adil E.; Murray, Joseph A.] Mayo Clin, Div Gastroentrol & Hepatol, Rochester, MN 55905 USA. [Ziegler, Georgia] Mayo Clin, Div Endocrinol, Rochester, MN 55905 USA. [Zinsmeister, Alan R.] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN 55905 USA. [Batey-Schaefer, Barbara] Northwestern Univ, Div Endocrinol, Chicago, IL 60611 USA. [Cleary, Patricia A.] George Washington Univ, Biostat Ctr, Washington, DC 20052 USA. [Cowie, Catherine] NIDDK, Div Diabet Endocrinol & Metab Dis, Washington, DC USA. [Lorenzi, Gayle] Univ Calif San Diego, Div Endocrinol, San Diego, CA 92103 USA. [Driscoll, Marsha; Harth, Judy] Univ Western Ontario, Div Endocrinol, London, ON, Canada. [Larkin, Mary; Christofi, Marielle; Nathan, David M.] Massachusetts Gen Hosp, Diabet Res Ctr, Boston, MA 02114 USA. [Bayless, Margaret] Univ Iowa, Gen Hosp, Div Endocrinol, Iowa City, IA USA. [Wimmergren, Nyra] Univ Minnesota, Div Endocrinol, Minneapolis, MN USA. [Herman, William; Martin, Cathy] Univ Michigan, Div Endocrinol, Ann Arbor, MI 48109 USA. [Whitehouse, Fred; Jones, Kim; Kruger, Davida] Henry Ford Medical New Ctr One, Dept Endocrinol, Detroit, MI USA. RP Bharucha, AE (reprint author), Mayo Clin, Div Gastroentrol & Hepatol, 200 First St SW, Rochester, MN 55905 USA. EM bharucha.adil@mayo.edu FU Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Disease [U01 DK094176, U01 DK094157]; National Eye Institute; National Institute of Neurologic Disorders and Stroke; General Clinical Research Centers Program; Clinical Translational Science Center Program, Bethesda, Maryland; US Public Health Service National Institutes of Health [P01 DK068055] FX The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications 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 Disease (current grant numbers U01 DK094176 and U01 DK094157), and through support by the National Eye Institute, the National Institute of Neurologic Disorders and Stroke, the General Clinical Research Centers Program (1993-2007), and the Clinical Translational Science Center Program (2006 to present), Bethesda, Maryland. This ancillary study was supported in part by US Public Health Service National Institutes of Health grant P01 DK068055 (A.E.B.). NR 47 TC 10 Z9 10 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD AUG PY 2015 VL 149 IS 2 BP 330 EP 339 DI 10.1053/j.gastro.2015.05.007 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CN4VX UT WOS:000358429600026 PM 25980755 ER PT J AU Welch, LC Litman, HJ Borba, CPC Vincenzi, B Henderson, DC AF Welch, Lisa C. Litman, Heather J. Borba, Christina P. C. Vincenzi, Brenda Henderson, David C. TI Does a Physician's Attitude toward a Patient with Mental Illness Affect Clinical Management of Diabetes? Results from a Mixed-Method Study SO HEALTH SERVICES RESEARCH LA English DT Article DE Clinical decision making; stigma; mental illness; diabetes ID HEALTH PROBLEMS; PSYCHIATRIC-PATIENTS; STIGMA; CARE; SCHIZOPHRENIA; DISEASE; DIAGNOSIS; DISORDERS; CHILDREN; DANGEROUSNESS AB ObjectiveTo determine whether physician's attitudes toward patients with comorbid mental illness affect management of a chronic disease. Data SourceA total of 256 primary care physicians interviewed in 2010. Study DesignThis randomized factorial experiment entailed physicians observing video vignettes of patient-actors with poorly controlled diabetes. Patients were balanced across age, gender, race, and comorbidity (schizophrenia with bizarre or normal affect, depression, eczema). Data CollectionPhysicians completed structured and semistructured interviews plus chart notes about clinical management and attitudes. Principal FindingsPhysicians reported more negative attitudes for patients with schizophrenia with bizarre affect (SBA). There were few differences in clinical decisions measured quantitatively or in charting, but qualitative data revealed less trust of patients with SBA as reporters, with more reliance on sources other than engaging the patient in care. Physicians often alerted colleagues about SBA, thereby shaping expectations before interactions occurred. ConclusionsResults are consistent with common stereotypes about people with serious mental illness. Vignettes did not include intentional indication of unreliable reporting or danger. Reducing health care disparities requires attention to subtle aspects of managing patientsparticularly those with atypical affectas seemingly slight differences could engender disparate patient experiences over time. C1 [Welch, Lisa C.] Tufts Med Ctr, Tufts Clin & Translat Sci Inst, Boston, MA 02111 USA. [Litman, Heather J.] Boston Childrens Hosp, Clin Res Ctr, Boston, MA USA. [Borba, Christina P. C.; Vincenzi, Brenda; Henderson, David C.] Massachusetts Gen Hosp, Schizophrenia Clin & Res Program, Boston, MA 02114 USA. [Borba, Christina P. C.; Henderson, David C.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Welch, LC (reprint author), Tufts Med Ctr, Tufts Clin & Translat Sci Inst, 800 Washington St,Box 63, Boston, MA 02111 USA. EM LWelch2@tuftsmedicalcenter.org FU National Institute of Mental Health [R01MH081824]; Otsuka; Novartis; EnVivo; Reckitt Benckiser FX Joint Acknowledgment/Disclosure Statement: The authors thank John B. McKinlay, Ph.D., for his insightful comments; David Pober, Ph.D., for statistical support; Candice Leonard, Ph.D., Almas Dossa, Ph.D., and Elizabeth Botelho, MA, for assistance with qualitative coding; and Karen Lutfey, PhD, for her leadership in conceptualizing the study, securing funding, and directing data collection as Principal Investigator from 2009 to 2012. This work was made possible by Grant Number R01MH081824 from the National Institute of Mental Health. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health. David Henderson declares grant/research support from Otsuka, Novartis, EnVivo, Reckitt Benckiser, and consultancies with NuPathe and Alkermes. NR 47 TC 1 Z9 1 U1 3 U2 9 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 2015 VL 50 IS 4 BP 998 EP 1020 DI 10.1111/1475-6773.12267 PG 23 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CN7KG UT WOS:000358612600005 PM 25487069 ER PT J AU Ryan, AM Burgess, JF Dimick, JB AF Ryan, Andrew M. Burgess, James F., Jr. Dimick, Justin B. TI Why We Should Not Be Indifferent to Specification Choices for Difference-in-Differences SO HEALTH SERVICES RESEARCH LA English DT Article DE Hospitals; econometrics; health economics; quality of care; health policy ID HEALTH-INSURANCE COVERAGE; PAY-FOR-PERFORMANCE; BARIATRIC SURGERY; MEDICARE BENEFICIARIES; FINANCIAL INCENTIVES; QUALITY IMPROVEMENT; PHYSICIAN PRACTICES; FEDERAL-EMPLOYEES; MENTAL-HEALTH; HOSPITAL PAY AB ObjectiveTo evaluate the effects of specification choices on the accuracy of estimates in difference-in-differences (DID) models. Data SourcesProcess-of-care quality data from Hospital Compare between 2003 and 2009. Study DesignWe performed a Monte Carlo simulation experiment to estimate the effect of an imaginary policy on quality. The experiment was performed for three different scenarios in which the probability of treatment was (1) unrelated to pre-intervention performance; (2) positively correlated with pre-intervention levels of performance; and (3) positively correlated with pre-intervention trends in performance. We estimated alternative DID models that varied with respect to the choice of data intervals, the comparison group, and the method of obtaining inference. We assessed estimator bias as the mean absolute deviation between estimated program effects and their true value. We evaluated the accuracy of inferences through statistical power and rates of false rejection of the null hypothesis. Principal FindingsPerformance of alternative specifications varied dramatically when the probability of treatment was correlated with pre-intervention levels or trends. In these cases, propensity score matching resulted in much more accurate point estimates. The use of permutation tests resulted in lower false rejection rates for the highly biased estimators, but the use of clustered standard errors resulted in slightly lower false rejection rates for the matching estimators. ConclusionsWhen treatment and comparison groups differed on pre-intervention levels or trends, our results supported specifications for DID models that include matching for more accurate point estimates and models using clustered standard errors or permutation tests for better inference. Based on our findings, we propose a checklist for DID analysis. C1 [Ryan, Andrew M.] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Burgess, James F., Jr.] Boston Univ, Sch Publ Hlth, US Dept Vet Affairs, Vet Affairs Boston Hlth Care Syst, Boston, MA USA. [Dimick, Justin B.] Univ Michigan, Sch Med, Dept Surg, Ctr Healthcare Outcomes & Policy, Ann Arbor, MI USA. RP Ryan, AM (reprint author), Univ Michigan, Sch Publ Hlth, 1415 Washington Hts,SPH 2 RM M3124, Ann Arbor, MI 48109 USA. EM amryan@umich.edu FU Agency for Healthcare Research and Quality [1 K01 HS018546]; National Institute on Aging [R01AG039434] FX Joint Acknowledgment/Disclosure Statement: The authors would like to acknowledge Jayme Mendelsohn for research assistance. Funding for Dr. Ryan was provided by a career development award from the Agency for Healthcare Research and Quality (1 K01 HS018546). Dr. Dimick was supported by a grant from the National Institute on Aging (R01AG039434). Dr. Dimick is a paid consultant and equity owner in ArborMetrix Inc., a company that provides software and analytic services for assessing hospital quality and efficiency. NR 66 TC 14 Z9 14 U1 1 U2 13 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 2015 VL 50 IS 4 BP 1211 EP 1235 DI 10.1111/1475-6773.12270 PG 25 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CN7KG UT WOS:000358612600016 PM 25495529 ER PT J AU Butt, AA Yan, P Bonilla, H Abou-Samra, AB Shaikh, OS Simon, TG Chung, RT Rogal, SS AF Butt, Adeel A. Yan, Peng Bonilla, Hector Abou-Samra, Abdul-Badi Shaikh, Obaid S. Simon, Tracey G. Chung, Raymond T. Rogal, Shari S. CA ERCHIVES Elect Retrieved Cohort TI Effect of addition of statins to antiviral therapy in hepatitis C virus-infected persons: Results from ERCHIVES SO HEPATOLOGY LA English DT Article ID HEPATOCELLULAR-CARCINOMA CELLS; RANDOMIZED CONTROLLED-TRIAL; CHRONIC LIVER-DISEASE; TREATMENT ELIGIBILITY; PULMONARY-FIBROSIS; RISK; HCV; SURVIVAL; COHORT; FLUVASTATIN AB 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been variably noted to affect hepatitis C virus (HCV) treatment response, fibrosis progression, and hepatocellular carcinoma (HCC) incidence, with some having a more potent effect than others. We sought to determine the impact of adding statins to antiviral therapy upon sustained virological response (SVR) rates, fibrosis progression, and HCC development among HCV-infected persons using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), an established, longitudinal, national cohort of HCV-infected veterans. Within ERCHIVES, we identified those who received HCV treatment and a follow-up of >24 months after treatment completion. We excluded those with human immunodeficiency virus coinfection, hepatitis B surface antigen positivity, cirrhosis, and HCC at baseline. Our main outcomes were liver fibrosis progression measured by FIB-4 scores, SVR rates, and incident HCC (iHCC). Among 7,248 eligible subjects, 46% received statin therapy. Statin use was significantly associated with attaining SVR (39.2% vs. 33.3%; P<0.01), decreased cirrhosis development (17.3% vs. 25.2%; P<0.001), and decreased iHCC (1.2% vs. 2.6%; P<0.01). Statins remained significantly associated with increased odds of SVR (odds ratio=1.44; 95% confidence interval [CI]=1.29, 1.61), but lower fibrosis progression rate, lower risk of progression to cirrhosis (hazard ratio [HR]=0.56; 95% CI=-0.50, 0.63), and of incident HCC (HR=0.51; 95% CI=0.34, 0.76) after adjusting for other relevant clinical factors. Conclusions: Statin use was associated with improved virological response (VR) rates to antiviral therapy and decreased progression of liver fibrosis and incidence of HCC among a large cohort of HCV-positive Veterans. These data support the use of statins in patients with HCV. (Hepatology 2015) Hepatology 2015;62:365-374 C1 [Butt, Adeel A.; Yan, Peng; Shaikh, Obaid S.; Rogal, Shari S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Butt, Adeel A.; Shaikh, Obaid S.; Rogal, Shari S.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. [Butt, Adeel A.; Abou-Samra, Abdul-Badi] Hamad Med Corp, Hamad Healthcare Qual Inst, Doha, Qatar. [Bonilla, Hector] ImmunoScience Inc, Pleasanton, CA USA. [Simon, Tracey G.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chung, Raymond T.] Harvard Univ, Sch Med, Boston, MA USA. RP Butt, AA (reprint author), Univ Pittsburgh, 3601 Fifth Ave,Suite 3A, Pittsburgh, PA 15213 USA. EM aabutt@hamad.qa OI Butt, Adeel/0000-0002-1118-1826 NR 50 TC 17 Z9 17 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD AUG PY 2015 VL 62 IS 2 BP 365 EP 374 DI 10.1002/hep.27835 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CN5EX UT WOS:000358453700010 PM 25847403 ER PT J AU Tapper, EB Finkelstein, D Mittleman, MA Piatkowski, G Lai, M AF Tapper, Elliot B. Finkelstein, Daniel Mittleman, Murray A. Piatkowski, Gail Lai, Michelle TI Standard assessments of frailty are validated predictors of mortality in hospitalized patients with cirrhosis SO HEPATOLOGY LA English DT Article ID CHRONIC LIVER-FAILURE; TRANSPLANT CANDIDATES; SURVIVAL; MODEL; RISK; MELD; DATABASES; ACCURACY; DISEASE; LIST AB The risk of morbidity and mortality for hospitalized patients with cirrhosis is high and incompletely captured by conventional indices. We sought to evaluate the predictive role of frailty in an observational cohort study of inpatients with decompensated cirrhosis between 2010 and 2013. The primary outcome was 90-day mortality. Secondary outcomes included discharge to a rehabilitation hospital, 30-day readmission, and length of stay. Frailty was assessed with three metrics: activities of daily living (ADL), the Braden Scale, and the Morse fall risk score. A predictive model was validated by randomly dividing the population into training and validation cohorts: 734 patients were admitted 1358 times in the study period. The overall 90-day mortality was 18.3%. The 30-day readmission rate was 26.6%, and the rate of discharge to a rehabilitation facility was 14.3%. Adjusting for sex, age, Model for End-Stage Liver Disease, sodium, and Charlson index, the odds ratio for the effect of an ADL score of less than 12 of 15 on mortality is 1.83 (95% confidence interval [CI] 1.05-3.20). A predictive model for 90-day mortality including ADL and Braden Scale yielded C statistics of 0.83 (95% CI 0.80-0.86) and 0.77 (95% CI 0.71-0.83) in the derivation and validation cohorts, respectively. Discharge to a rehabilitation hospital is predicted by both the ADL (<12) and Braden Scale (<16), with respective adjusted odds ratios of 3.78 (95% CI 1.97-7.29) and 6.23 (95% CI 2.53-15.4). Length of stay was associated with the Braden Scale (<16) (hazard ratio=0.63, 95% CI 0.44-0.91). No frailty measure was associated with 30-day readmission. Conclusions: Readily available, standardized measures of frailty predict 90-day mortality, length of stay, and rehabilitation needs for hospitalized patients with cirrhosis. (Hepatology 2015;62:584-590 C1 [Tapper, Elliot B.; Lai, Michelle] Harvard Univ, Sch Med, Div Gastroenterol & Hepatol, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Finkelstein, Daniel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Mittleman, Murray A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Cardiovasc Epidemiol Res Unit, Boston, MA 02215 USA. [Piatkowski, Gail] Harvard Univ, Beth Israel Deaconess Med Ctr, Decis Support, Sch Med, Boston, MA 02215 USA. RP Tapper, EB (reprint author), Harvard Univ, Sch Med, Div Gastroenterol & Hepatol, Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215 USA. EM etapper@bidmc.harvard.edu FU NCATS NIH HHS [UL1 TR001102] NR 30 TC 18 Z9 18 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD AUG PY 2015 VL 62 IS 2 BP 584 EP 590 DI 10.1002/hep.27830 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CN5EX UT WOS:000358453700029 PM 25846824 ER PT J AU Tashima, KT Mollan, KR Na, L Gandhi, RT Klingman, KL Fichtenbaum, CJ Andrade, A Johnson, VA Eron, JJ Smeaton, L Haubrich, RH AF Tashima, Karen T. Mollan, Katie R. Na, Lumine Gandhi, Rajesh T. Klingman, Karin L. Fichtenbaum, Carl J. Andrade, Adriana Johnson, Victoria A. Eron, Joseph J. Smeaton, Laura Haubrich, Richard H. TI Regimen selection in the OPTIONS trial of HIV salvage therapy: drug resistance, prior therapy, and race-ethnicity determine the degree of regimen complexity SO HIV CLINICAL TRIALS LA English DT Article DE HIV drug resistance; Treatment-experienced; Phenotypic susceptibility score; Tropism; cPSS; Antiretroviral therapy ID TREATMENT-EXPERIENCED PATIENTS; SOCIETY-USA PANEL; PHENOTYPIC SUSCEPTIBILITY; PROTEASE INHIBITORS; INFECTION; EFFICACY; LAMIVUDINE; RITONAVIR; SAFETY; RECOMMENDATIONS AB Background: Regimen selection for highly treatment-experienced patients is complicated. Methods: Using a web-based utility, study team members reviewed antiretroviral (ARV) history and resistance data and recommended individual ARV regimens and nucleoside reverse transcriptase inhibitor (NRTI) options for treatment-experienced participants consisting of 3-4 of the following agents: raltegravir (RAL), darunavir (DRV)/ritonavir, tipranavir (TPV)/ritonavir, etravirine (ETR), maraviroc (MVC), and enfuvirtide (ENF). We evaluated team recommendations and site selection of regimen and NRTIs. Associations between baseline factors and the selection of a complex regimen (defined as including four ARV agents or ENF) were explored with logistic regression. Results: A total of 413 participants entered the study. Participants initiated the first or second recommended regimen 86% of the time and 21% of participants started a complex regimen. In a multivariable model, ARV resistance to NRTI (odds ratio [OR] =2.2), non-nucleoside reverse transcriptase inhibitor (NNRTI, OR=6.2) or boosted protease inhibitor (PI, OR=6.6), prior use of integrase strand transfer inhibitor (INSTI, OR=25), and race-ethnicity (all P <= 0.01) were associated with selection of a complex regimen. Black non-Hispanic (OR=0.5) and Hispanic participants from the continental US (OR=0.2) were less likely to start a complex regimen, compared to white non-Hispanics. Conclusions: In this multi-center trial, we developed a web-based utility that facilitated treatment recommendations for highly treatment-experienced patients. Drug resistance, prior INSTI use, and race-ethnicity were key factors in decisions to select a more complex regimen. C1 [Tashima, Karen T.] Brown Univ, Warren Alpert Med Sch, Miriam Hosp, Providence, RI 02906 USA. [Mollan, Katie R.; Na, Lumine; Smeaton, Laura] Harvard Univ, TH Chan Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Mollan, Katie R.] Univ N Carolina, Chapel Hill, NC USA. [Gandhi, Rajesh T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gandhi, Rajesh T.] Ragon Inst, Boston, MA USA. [Klingman, Karin L.] NIAID, HIV Res Branch TRP, DAIDS, NIH, Bethesda, MD 20892 USA. [Fichtenbaum, Carl J.] Univ Cincinnati, Cincinnati, OH 45267 USA. [Andrade, Adriana] Johns Hopkins Univ, Baltimore, MD USA. [Johnson, Victoria A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Johnson, Victoria A.] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA. [Eron, Joseph J.] Univ North Carolina Chapel Hill, Chapel Hill, NC USA. [Haubrich, Richard H.] Gilead Sci Inc, Foster City, CA USA. [Haubrich, Richard H.] Univ Calif San Diego, La Jolla, CA 92093 USA. RP Tashima, KT (reprint author), Brown Univ, Warren Alpert Med Sch, Miriam Hosp, 164 Summit Ave, Providence, RI 02906 USA. EM ktashima@lifespan.org; fichtecj@ucmail.uc.edu FU National Institute of Allergy and Infectious Diseases (NIAID) [UM1AI068636]; National Institute of Mental Health (NIMH); National Institute of Dental and Craniofacial Research (NIDCR); NIAID [AI68634]; National Institutes of Health (NIH) [UM1 AI 069412, P30 AI042853, P30 AI50410, AI 064086, AI 069432, AI 36214, K24, R01 AI066992-04A1]; AIDS Clinical Trials Group [NIH U01 AI 694722, UM1 AI069501]; Harvard University Center for AIDS Research [NIH 2P30 AI060354-06] FX The project described was supported by Award Number UM1AI068636 from the National Institute of Allergy and Infectious Diseases (NIAID) and supported by National Institute of Mental Health (NIMH), National Institute of Dental and Craniofacial Research (NIDCR). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIAID or the National Institutes of Health. The work was also supported by the Statistical and Data Management Center (SDMC) grant [AI68634] from the NIAID. Boehringer-Ingelheim, Hoffmann-La Roche, Janssen, Merck, and Pfizer provided study medications and Monogram Biosciences provided HIV genotype and phenotype resistance and HIV tropism testing. KTT: UM1 AI 069412 and P30 AI042853 (Lifespan/Tufts/Brown CFAR), P30 AI50410 (UNC-KM), AI 064086 (K24 to RH), AI 069432 (UCSD ACTU), AI 36214 (UCSD CFAR Clinical Investigation and Biostatistics Core) RTG is supported by National Institutes of Health (NIH) [R01 AI066992-04A1] and by grants to the AIDS Clinical Trials Group (NIH U01 AI 694722) and the Harvard University Center for AIDS Research (NIH 2P30 AI060354-06). CJF is supported by UM1 AI069501 from the AIDS Clinical Trials Group. NR 20 TC 1 Z9 1 U1 0 U2 15 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1528-4336 EI 1945-5771 J9 HIV CLIN TRIALS JI HIV Clin. Trials PD AUG PY 2015 VL 16 IS 4 BP 147 EP 156 DI 10.1179/1945577115Y.0000000001 PG 10 WC Infectious Diseases; Pharmacology & Pharmacy SC Infectious Diseases; Pharmacology & Pharmacy GA CN8ZB UT WOS:000358733700004 PM 26212575 ER PT J AU Chen, YW Chiu, YW Chen, CY Chuang, SK AF Chen, Y. -W. Chiu, Y. -W. Chen, C. -Y. Chuang, S. -K. TI Botulinum toxin therapy for temporomandibular joint disorders: a systematic review of randomized controlled trials SO INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Review DE botulinum toxin; clinical trials; efficacy; myofascial pain; review; temporomandibular joint ID MYOFASCIAL PAIN; INJECTION; TMD AB The objective of this study was to undertake a systematic review to assess the efficacy of botulinum toxin therapy (BTX) for temporomandibular joint disorders (TMDs). A comprehensive search of major databases through PubMed, EMBASE, and Cochrane CENTRAL was conducted to locate all relevant articles published from inception to October 2014. Eligible studies were selected based on inclusion criteria and included English language, peer-reviewed publications of randomized controlled trials comparing BTX versus any alternative intervention or placebo. Quality assessment and data extraction were done according to the Cochrane risk of bias tool and recommendations. The entire systematic search and selection process was done independently by two reviewers. Five relevant study trials were identified, involving 117 participants. Two trials revealed a significant between-group difference in myofascial pain reduction, another trial that compared BTX with fascial manipulation showed equal efficacy of pain relief on TMDs, while the remaining two trials showed no significant difference between the BTX and placebo groups. Because of considerable variations in study methods and evaluation of results, a meta-analysis could not be performed. Based on this review, no consensus could be reached on the therapeutic benefits of BTX on TMDs. A more rigorous design of trials should be carried out in future studies. C1 [Chen, Y. -W.; Chiu, Y. -W.] Taipei Vet Gen Hosp, Dept Stomatol, Taipei, Taiwan. [Chen, Y. -W.; Chen, C. -Y.] Natl Yang Ming Univ, Sch Dent, Taipei 112, Taiwan. [Chen, Y. -W.] Natl Yang Ming Univ, Inst Clin Med, Taipei 112, Taiwan. [Chen, Y. -W.; Chuang, S. -K.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Chen, Y. -W.; Chuang, S. -K.] Harvard Univ, Sch Dent Med, Boston, MA 02114 USA. [Chen, C. -Y.] Univ Maryland, Sch Dent, Dept Pediat Dent, Baltimore, MD 21201 USA. RP Chuang, SK (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM sungkiangchuang@gmail.com NR 33 TC 3 Z9 3 U1 1 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0901-5027 EI 1399-0020 J9 INT J ORAL MAX SURG JI Int. J. Oral Maxillofac. Surg. PD AUG PY 2015 VL 44 IS 8 BP 1018 EP 1026 DI 10.1016/j.ijom.2015.04.003 PG 9 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA CN7PR UT WOS:000358627000014 PM 25920597 ER PT J AU Umezaki, Y Badran, BW Gonzales, TS George, MS AF Umezaki, Y. Badran, B. W. Gonzales, T. S. George, M. S. TI Daily left prefrontal repetitive transcranial magnetic stimulation for medication-resistant burning mouth syndrome SO INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article DE burning mouth syndrome; transcranial magnetic stimulation; chronic pain; left dorsolateral prefrontal cortex ID PAIN; CORTEX AB Burning mouth syndrome (BMS) is a persistent and chronic burning sensation in the mouth in the absence of any abnormal organic findings. The pathophysiology of BMS is unclear and its treatment is not fully established. Although antidepressant medication is commonly used for treatment, there are some medication-resistant patients, and a new treatment for medication-resistant BMS is needed. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technology approved by the US Food and Drug Administration (FDA) for the treatment of depression. Recent studies have found beneficial effects of TMS for the treatment of pain. A case of BMS treated successfully with daily left prefrontal rTMS over a 2-week period is reported here. Based on this patient's clinical course and a recent pain study, the mechanism by which TMS may act to decrease the burning pain is discussed. C1 [Umezaki, Y.; Badran, B. W.; George, M. S.] Med Univ S Carolina, Dept Psychiat, Brain Stimulat Lab, Charleston, SC 29425 USA. [Gonzales, T. S.] Med Univ S Carolina, Coll Dent Med, Div Oral Pathol, Charleston, SC 29425 USA. [George, M. S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Umezaki, Y (reprint author), Med Univ S Carolina, Dept Psychiat, Brain Stimulat Lab, 67 President St, Charleston, SC 29425 USA. EM umezaki@yahoo.com NR 10 TC 0 Z9 0 U1 3 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0901-5027 EI 1399-0020 J9 INT J ORAL MAX SURG JI Int. J. Oral Maxillofac. Surg. PD AUG PY 2015 VL 44 IS 8 BP 1048 EP 1051 DI 10.1016/j.ijom.2015.04.008 PG 4 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA CN7PR UT WOS:000358627000019 PM 25979192 ER PT J AU Oestreich, LKL Mifsud, NG Ford, JM Roach, BJ Mathalon, DH Whitford, TJ AF Oestreich, Lena K. L. Mifsud, Nathan G. Ford, Judith M. Roach, Brian J. Mathalon, Daniel H. Whitford, Thomas J. TI Subnormal sensory attenuation to self-generated speech in schizotypy: Electrophysiological evidence for a 'continuum of psychosis' SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Article DE Electroencephalography (EEG); Sensory suppression; Schizophrenia; Schizotypy; Continuum of psychosis; Self-monitoring; Event-related potential (ERP) ID COROLLARY DISCHARGE DYSFUNCTION; PRIMATE AUDITORY-CORTEX; SCHIZOPHRENIA; RESPONSES; DISORDERS; CRITERIA; THINKING; TALKING; HUMANS; AGENCY AB Background: A 'continuum of psychosis' refers to the concept that psychotic-like experiences occur to certain extents in the healthy population and to more severe extents in individuals with psychotic disorders. If this concept is valid, neurophysiological abnormalities exhibited by patients with schizophrenia should also be present, to some degree, in non-clinical individuals who score highly on the personality dimension of schizotypy. Patients with schizophrenia have consistently been shown to exhibit electrophysiological suppression abnormalities to self-generated speech. The present study aimed to investigate whether these electrophysiological suppression abnormalities were also present in non-clinical individuals who scored highly on schizotypy. Methods: Thirty-seven non-clinical individuals scoring High (above median) and 37 individuals scoring Low (below median) on the Schizotypal Personality Questionnaire (SPQ; a commonly used schizotypy scale) underwent electroencephalographic (EEG) recording. The amplitude of the N1 component of the auditory-evoked potential was measured while participants (a) vocalized simple syllables (Talk condition), (b) passively listened to a recording of these vocalizations (Listen condition) and (c) listened to a recording of the vocalizations while simultaneously watching a video depicting the sound-wave of the forthcoming vocalizations, allowing them to be temporally predicted (Cued Listen condition). Results: The Low Schizotypy group exhibited significantly reduced N1-amplitude in the Talk condition relative to both the Listen and Cued Listen conditions; that is, they exhibited significant N1-suppression. The High Schizotypy group exhibited significantly lower levels of N1-suppression compared to the Low Schizotypy group. Furthermore, while the Cued Listen condition induced significantly lower N1-amplitudes compared to the Listen condition in the Low Schizotypy group, this was not the case for the High Schizotypy group. Conclusions: The results suggest that non-clinical, highly schizotypal individuals exhibit subnormal levels of N1-suppression to self-generated speech, similar to the N1-suppression abnormalities which have previously been reported in patients with schizophrenia. This finding provides empirical support for the existence of a neurophysiological 'continuum of psychosis'. (C) 2015 Elsevier B.V. All rights reserved. C1 [Oestreich, Lena K. L.; Mifsud, Nathan G.; Whitford, Thomas J.] UNSW Australia, Sch Psychol, Sydney, NSW 2052, Australia. [Ford, Judith M.; Roach, Brian J.; Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, Brain Imaging & EEG Lab BIEEGL, San Francisco, CA USA. [Oestreich, Lena K. L.; Ford, Judith M.; Mathalon, Daniel H.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Whitford, TJ (reprint author), UNSW Australia, Sch Psychol, Sydney, NSW 2052, Australia. EM t.whitford@unsw.edu.au OI Mifsud, Nathan/0000-0001-7794-8041; Oestreich, Lena/0000-0002-4978-7794 FU Australian Research Council [DP140104394]; National Health and Medical Research Council of Australia [APP1090507]; NARSAD Brain and Behavior Research Foundation [17537]; VA Merit Review [I01 CX000497]; NIMH [R01 MH-58262] FX Thomas Whitford is supported by a Discovery Project from the Australian Research Council (DP140104394), a Career Development Fellowship from the National Health and Medical Research Council of Australia (APP1090507), and a Young Investigator Award (Barbara and John Streicker Investigator) from the NARSAD Brain and Behavior Research Foundation (17537). Judith Ford's contributions to this work were supported by VA Merit Review (I01 CX000497) and NIMH (R01 MH-58262) grants. NR 50 TC 6 Z9 6 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 EI 1872-7697 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD AUG PY 2015 VL 97 IS 2 BP 131 EP 138 DI 10.1016/j.ijpsycho.2015.05.014 PG 8 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA CN5JT UT WOS:000358466300007 PM 26027781 ER PT J AU Hannon, N Arsava, EM Audebert, HJ Ay, H Crowe, M Ni Chroinin, D Furie, K McGorrian, C Molshatzki, N Murphy, S Noone, I O'Donnell, M Schenkel, J Tan, KM Tanne, D Kelly, PJ AF Hannon, Niamh Arsava, Ethem M. Audebert, Heinrich J. Ay, Hakan Crowe, Morgan Ni Chroinin, Danielle Furie, Karen McGorrian, Catherine Molshatzki, Noa Murphy, Sean Noone, Imelda O'Donnell, Martin Schenkel, Johannes Tan, Kit M. Tanne, David Kelly, Peter J. TI Antithrombotic treatment at onset of stroke with atrial fibrillation, functional outcome, and fatality: a systematic review and meta-analysis SO INTERNATIONAL JOURNAL OF STROKE LA English DT Review DE anticoagulation; atrial fibrillation; prevention; stroke; warfarin ID ISCHEMIC-STROKE; ORAL ANTICOAGULATION; SEVERITY; WARFARIN; RIVAROXABAN; PREVENTION; DABIGATRAN; THERAPY; AGENTS AB BackgroundIn atrial fibrillation-associated stroke, conflicting data exist regarding association between therapeutic vitamin K-antagonist anticoagulation (International Normalized Ratio 2-3) and early death and functional outcome, and few data exist relating to late outcome in ischemic and haemorrhagic atrial fibrillation-stroke. AimWe performed a systematic review and meta-analysis of oral anticoagulation at stroke onset, death and functional outcome. MethodsWe performed a systematic review, searching multiple sources. Studies were included if outcomes in atrial fibrillation-associated stroke were reported stratified by pre-stroke antithrombotic status, with documented International Normalized Ratio at onset. Outcomes were survival and good functional outcome (modified Rankin score 0-2) at discharge/30 days, and at one-year. ResultsOf eight studies (3552 patients) in ischemic stroke, International Normalized Ratio2 compared with other treatments (International Normalized Ratio<2, antiplatelet, or no antithrombotic) was associated with good outcome [pooled odds ratio 19 (95% confidence interval) 15-25, P<0001] and improved survival at 30 daysdischarge (pooled odds ratio for death 04, confidence interval 02-05, P<0001). The net benefit remained after inclusion of haemorrhagic stroke (odds ratio for good outcome 189, confidence interval 145-246, P<0001). At one-year, improved functional outcome for International Normalized Ratio2 (pooled odds ratio 17, confidence interval 10-27, P=004) and survival (odds ratio for death 05, confidence interval 04-08, P=0001) were also observed. ConclusionsTherapeutic International Normalized Ratio at stroke onset was associated with early and late improved survival and functional recovery suggesting sustained benefit for warfarin anticoagulation for stroke outcome in atrial fibrillation patients. Long-term outcome data following stroke in patients taking new oral anticoagulants is required. C1 [Hannon, Niamh; Ni Chroinin, Danielle; McGorrian, Catherine; Murphy, Sean; Kelly, Peter J.] UCD DAMC, Neurovasc Unit Neurovasc Unit Translat & Therapeu, Dublin, Ireland. [Arsava, Ethem M.; Ay, Hakan; Furie, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Audebert, Heinrich J.] Charite, Berlin, Germany. [Crowe, Morgan; Noone, Imelda; Tan, Kit M.] St Vincents Univ Hosp, Dublin 4, Ireland. [Molshatzki, Noa; Tanne, David] Chaim Sheba Med Ctr, Tel Aviv, Israel. [Molshatzki, Noa; Tanne, David] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. [O'Donnell, Martin] McMaster Univ, Hamilton, ON, Canada. [Schenkel, Johannes] Stadt Klinikum Munchen GmbH, Klinikum Harlaching, Munich, Germany. RP Kelly, PJ (reprint author), Mater Univ Hosp, UCD DAMC Catherine McAuley Res Ctr, Neurovasc Unit Translat & Therapeut Res, 27 Nelson St, Dublin 7, Ireland. EM niamh.hannon@addenbrookes.nhs.uk RI Tan, Kit Mun/D-5301-2013; OI O'Donnell, Martin/0000-0002-7347-7761 FU Bavarian health insurance funds; Bavarian Ministry of Social Affairs Family and Women; German Stroke Foundation; German Federal Minstry of Education and Research (BMBF) within the Stroke Competence Network; Irish Heart Foundation; Health Research Board of Ireland FX The TEMPiS study was funded by the Bavarian health insurance funds, the Bavarian Ministry of Social Affairs Family and Women, the German Stroke Foundation and the German Federal Minstry of Education and Research (BMBF) within the Stroke Competence Network. Prof Kelly is funded by the Irish Heart Foundation and a Clinician Scientist Award from the Health Research Board of Ireland. NR 31 TC 1 Z9 2 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD AUG PY 2015 VL 10 IS 6 BP 808 EP 814 DI 10.1111/ijs.12473 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CN5EB UT WOS:000358451500016 PM 25808552 ER PT J AU Mascitelli, JR Oermann, EK De Leacy, RA Moyle, H Mocco, J Patel, AB AF Mascitelli, Justin R. Oermann, Eric K. De Leacy, Reade A. Moyle, Henry Mocco, J. Patel, Aman B. TI Predictors of treatment failure following coil embolization of intracranial aneurysms SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Coil embolization; Intracranial aneurysm; Recurrence; Treatment failure ID STENT-ASSISTED COILING; PLATINUM SCIENCE TRIAL; PACKING DENSITY; ENDOVASCULAR TREATMENT; CEREBRAL ANEURYSMS; DETACHABLE COILS; UNRUPTURED ANEURYSMS; RANDOMIZED-TRIAL; FLUID-DYNAMICS; RECANALIZATION AB We present a retrospective review of 357 consecutive patients with 419 aneurysms treated with coil embolization. Although incomplete occlusion and recurrence of intracranial aneurysms following coil embolization is a well-known problem, the factors that influence and predict treatment failure are still debated. For this study, we excluded non-coiling endovascular techniques (flow diversion) and non-saccular aneurysms (fusiform). The modified Raymond Roy occlusion classification (MRRC) was used to grade the aneurysms. Treatment failure was defined as filling of the aneurysm dome (MRRC Class Ilia or Bib) at the first angiographic follow-up (average 8 months). Univariate statistical tests were employed to select variables for incorporation into a multivariable logistic regression model. Multivariate analysis identified greater aneurysm volume (p <0.001), packing density (PD) less than 31% (p = 0.007) and initial MRRC Class IIIb (p < 0.001) as predictors of treatment failure. Incomplete neck coverage with coils was associated with treatment failure in univariate but not multivariate analysis. Class IIIb status was more predictive of treatment failure compared to all Class III (odds ratio 168 versus 14.4). Clinical outcomes were similar in both groups except that there were more retreatments in the treatment failure group (p < 0.001). Aneurysm volume, PD and initial occlusion class are associated with angiographic outcome, consistent with prior literature. The MRRC is a powerful predictor of treatment failure. These results will be useful in the effort to both prevent and predict treatment failure after coil embolization, however, they should be verified in a prospective study. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Patel, Aman B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. [Mascitelli, Justin R.; Oermann, Eric K.; De Leacy, Reade A.; Mocco, J.] Icahn Sch Med Mt Sinai, Dept Neurosurg, New York, NY 10029 USA. [Oermann, Eric K.] Icahn Sch Med Mt Sinai, Inst Genom & Multiscale Biol, New York, NY 10029 USA. [Moyle, Henry] Columbia Neurosurg Network, West Long Branch, NJ USA. RP Patel, AB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, 15 Parkman St,WAC 745, Boston, MA 02114 USA. EM aman.patel@mountsinai.org NR 49 TC 4 Z9 4 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 EI 1532-2653 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD AUG PY 2015 VL 22 IS 8 BP 1275 EP 1281 DI 10.1016/j.jocn.2015.03.002 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CN4GZ UT WOS:000358389900012 PM 25986179 ER PT J AU Redjal, N Agarwalla, PK Dietrich, J Dinevski, N Stemmer-Rachamimov, A Nahed, BV Loeffler, JS AF Redjal, Navid Agarwalla, Pankaj K. Dietrich, Jorg Dinevski, Nikolaj Stemmer-Rachamimov, Anat Nahed, Brian V. Loeffler, Jay S. TI Remote acute demyelination after focal proton radiation therapy for optic nerve meningioma SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Demyelination; Edema; Meningioma; Optic nerve; Proton beam; Stereotactic radiotherapy ID SHEATH MENINGIOMA; SKULL BASE; TUMORS; RADIOTHERAPY AB We present a unique patient with delayed onset, acute demyelination that occurred distant to the effective field of radiation after proton beam radiotherapy for an optic nerve sheath meningioma. The use of stereotactic radiotherapy as an effective treatment modality for some brain tumors is increasing, given technological advances which allow for improved targeting precision. Proton beam radiotherapy improves the precision further by reducing unnecessary radiation to surrounding tissues. A 42-year-old woman was diagnosed with an optic nerve sheath meningioma after initially presenting with vision loss. After biopsy of the lesion to establish diagnosis, the patient underwent stereotactic proton beam radiotherapy to a small area localized to the tumor. Subsequently, the patient developed a large enhancing mass-like lesion with edema in a region outside of the effective radiation field in the ipsilateral frontal lobe. Given imaging features suggestive of possible primary malignant brain tumor, biopsy of this new lesion was performed and revealed an acute demyelinating process. This patient illustrates the importance of considering delayed onset acute demyelination in the differential diagnosis of enhancing lesions in patients previously treated with radiation. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Redjal, Navid; Agarwalla, Pankaj K.; Nahed, Brian V.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Dietrich, Jorg; Dinevski, Nikolaj] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Stemmer-Rachamimov, Anat] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Loeffler, Jay S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Redjal, N (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St, Boston, MA 02114 USA. EM nredjal@mgh.harvard.edu NR 15 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 0967-5868 EI 1532-2653 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD AUG PY 2015 VL 22 IS 8 BP 1367 EP 1369 DI 10.1016/j.jocn.2015.02.017 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CN4GZ UT WOS:000358389900031 PM 25937571 ER PT J AU Kojima, M Puppa, G Kirsch, R Basturk, O Frankel, WL Vieth, M Lugli, A Sheahan, K Yeh, M Lauwers, GY Risio, M Shimazaki, H Iwaya, K Kage, M Akiba, J Ohkura, Y Horiguchi, S Shomori, K Kushima, R Nomura, S Ajioka, Y Adsay, V Ochiai, A AF Kojima, Motohiro Puppa, Giacomo Kirsch, Richard Basturk, Olca Frankel, Wendy L. Vieth, Michael Lugli, Alessandro Sheahan, Kieran Yeh, Matthew Lauwers, Greg Y. Risio, Mauro Shimazaki, Hideyuki Iwaya, Keiichi Kage, Masayoshi Akiba, Jun Ohkura, Yasuo Horiguchi, Shinichiro Shomori, Kohei Kushima, Ryoji Nomura, Shogo Ajioka, Yoichi Adsay, Volkan Ochiai, Atsushi TI Blood and lymphatic vessel invasion in pT1 colorectal cancer: an international concordance study SO JOURNAL OF CLINICAL PATHOLOGY LA English DT Article ID VASCULAR INVASION; LYMPHOVASCULAR INVASION; NODE METASTASIS; VENOUS INVASION; CARCINOMA; INTEROBSERVER; VARIABILITY; PATHOLOGY; RECTUM; COLON AB Aim This study was performed to evaluate the concordance in pathological assessments of blood and lymphatic vessel invasion (BLI) in pT1 colorectal cancers and to assess the effect of diagnostic criterion on consistency in the assessment of BLI. Methods Forty consecutive patients undergoing surgical resection of pT1 colorectal cancers were entered into this study. H&E-stained, D2-40-stained and elastica-stained slides from the tumours were examined by 18 pathologists from seven countries. The 40 cases were divided into two cohorts with 20 cases each. In cohort 1, pathologists diagnosed BLI using criteria familiar to them; all Japanese pathologists used a criterion of BLI from the Japanese Society for Cancer of the Colon and Rectum (JSCCR). In cohort 2, all pathologists used the JSCCR diagnostic criterion. Results In cohort 1, diagnostic concordance was moderate in the US/Canadian and European pathologists. There were no differences in the consistency compared with results for Japanese pathologists, and no improvement in the diagnostic concordance was found for using the JSCCR criterion. However, in cohort 2, the JSCCR criterion decreased the consistency of BLI diagnosis in the US/Canadian and European pathologists. The level of decreased consistency in the assessment of BLI was different between the US/Canadian and European pathologists. Conclusions A uniform criterion strongly influences the diagnostic consistency of BLI but may not always improve the concordance. Further study is required to achieve an objective diagnosis of BLI in colorectal cancer. The varying effects of diagnostic criterion on the pathologists from Japan, the USA/Canada and Europe might reflect varied interpretations of the criterion. Internationally accepted criterion should be developed by participants from around the world. C1 [Kojima, Motohiro; Ochiai, Atsushi] Natl Canc Ctr Hosp East, Res Ctr Innovat Oncol, Div Pathol, Kashiwa, Chiba 2778577, Japan. [Puppa, Giacomo] Hop Univ Geneve 1, Dept Pathol, Geneva, Switzerland. [Kirsch, Richard] Mt Sinai Hosp, Dept Pathol & Lab Med, Toronto, ON M5G 1X5, Canada. [Basturk, Olca] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Frankel, Wendy L.] Ohio State Univ, Dept Pathol, Med Ctr, Columbus, OH 43210 USA. [Vieth, Michael] Inst Pathol, Bayreuth, Germany. [Lugli, Alessandro] Univ Bern, Inst Pathol, Bern, Switzerland. [Sheahan, Kieran] St Vincents Univ Hosp, Dept Pathol, Dublin 4, Ireland. [Yeh, Matthew] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. [Lauwers, Greg Y.] Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Boston, MA 02114 USA. [Risio, Mauro] IRCCS, Candiolo Canc Inst FPO, Dept Pathol, Turin, Italy. [Shimazaki, Hideyuki; Iwaya, Keiichi] Natl Def Med Coll, Dept Pathol, Saitama, Japan. [Kage, Masayoshi] Kurume Univ Hosp, Dept Diagnost Pathol, Fukuoka, Japan. [Akiba, Jun] Kurume Univ, Sch Med, Dept Pathol, Fukuoka, Japan. [Ohkura, Yasuo] Kyorin Univ, Grad Sch Med, Dept Pathol, Tokyo, Japan. [Horiguchi, Shinichiro] Tokyo Metropolitan Komagome Hosp, Dept Pathol, Tokyo, Japan. [Shomori, Kohei] Sanin Rosai Hosp, Div Pathol, Tottori, Japan. [Kushima, Ryoji] Shiga Univ Med Sci Hosp, Div Diagnost Pathol, Otsu, Shiga, Japan. [Nomura, Shogo] Natl Canc Ctr, Ctr Res Adm & Support, Div Biostat, Tokyo 104, Japan. [Ajioka, Yoichi] Niigata Univ, Grad Sch Med & Dent Sci, Dept Pathol, Niigata, Japan. [Adsay, Volkan] Emory Univ, Sch Med, Pathol & Lab Med, Atlanta, GA USA. RP Ochiai, A (reprint author), Natl Canc Ctr Hosp East, Res Ctr Innovat Oncol, Div Pathol, 6-5-1 Kashiwanoha, Kashiwa, Chiba 2778577, Japan. EM aochiai@east.ncc.go.jp RI Kirsch, Richard/J-2335-2016 FU Japanese Society for Cancer of the Colon and Rectum (JSCCR); Ministry of Health, Labor and Welfare, Japan [26-A-8, 19] FX This work was supported by the Japanese Society for Cancer of the Colon and Rectum (JSCCR) and Grant-in-Aid for Cancer Research (26-A-8, 19) from the Ministry of Health, Labor and Welfare, Japan. NR 27 TC 2 Z9 2 U1 0 U2 8 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0021-9746 EI 1472-4146 J9 J CLIN PATHOL JI J. Clin. Pathol. PD AUG PY 2015 VL 68 IS 8 BP 628 EP 632 DI 10.1136/jclinpath-2014-202805 PG 5 WC Pathology SC Pathology GA CN7AP UT WOS:000358586200007 PM 25934844 ER PT J AU Tan, ASL Lee, CJ Chae, J AF Tan, Andy S. L. Lee, Chul-joo Chae, Jiyoung TI Exposure to Health (Mis)Information: Lagged Effects on Young Adults' Health Behaviors and Potential Pathways SO JOURNAL OF COMMUNICATION LA English DT Article DE Information; Misinformation; Belief; Intention; Behavior; Young Adults; United States ID INFORMATION-SEEKING; PUBLIC-HEALTH; MISSING DATA; CANCER; MISINFORMATION; SCIENCE; BELIEFS; MODEL; COMMUNICATION; KNOWLEDGE AB Consumers frequently encounter competing health information comprised of accurate and erroneous messages about different diseases. This longitudinal study examined the lagged associations between young adults' exposure to health (mis)information about 4 cancer-related risk factors (indoor tanning, e-cigarette use, reusing plastic bottles, and artificial sweeteners), beliefs, intentions, and behaviors as informed by theories of persuasion and behavior change. We found significant lagged associations between health (mis)information exposure and beliefs for three topics; beliefs predicted subsequent intentions for 2 topics; and intentions predicted subsequent behaviors for 4 topics. The hypothesized pathway of effects was supported for 2 topics. These findings provide insights for developing theory in the area of (mis)information effects and for designing interventions that mitigate the adverse consequences of misinformation. C1 [Tan, Andy S. L.] Harvard Univ, Dept Social & Behav Sci, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Tan, Andy S. L.] Dana Farber Canc Inst, Div Populat Sci, Ctr Community Based Res, Boston, MA 02115 USA. [Lee, Chul-joo] Seoul Natl Univ, Dept Commun, Seoul, South Korea. [Chae, Jiyoung] Natl Univ Singapore, Dept Commun & New Media, Singapore 117548, Singapore. RP Tan, ASL (reprint author), Harvard Univ, Dept Social & Behav Sci, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. EM andy_tan@dfci.harvard.edu FU SNU Invitation Program for Distinguished Scholar; ICT R&D program of MSIP/IITP [2013-005-002-013] FX C.J. Lee acknowledges the support of the SNU Invitation Program for Distinguished Scholar and the ICT R&D program of MSIP/IITP [2013-005-002-013, How to create an ICT-based eco-system for content industry] for this research. NR 68 TC 1 Z9 1 U1 6 U2 30 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9916 EI 1460-2466 J9 J COMMUN JI J. Commun. PD AUG PY 2015 VL 65 IS 4 BP 674 EP 698 DI 10.1111/jcom.12163 PG 25 WC Communication SC Communication GA CN8MT UT WOS:000358695900007 ER PT J AU Allister, LM Schultz, ML Brown, DFM Miller, ES AF Allister, Lauren M. Schultz, Megan L. Brown, David F. M. Miller, Emily S. TI ALTERED MENTAL STATUS AND FEVER SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID POSITIVE MONOSPOT TEST; CEREBRAL MALARIA; RETURNING TRAVELER; FALCIPARUM-MALARIA; CHILDREN; RETINOPATHY C1 [Allister, Lauren M.; Brown, David F. M.; Miller, Emily S.] Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. [Allister, Lauren M.; Brown, David F. M.; Miller, Emily S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Schultz, Megan L.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02114 USA. [Schultz, Megan L.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Miller, ES (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Zero Emerson Pl,Suite 3B, Boston, MA 02114 USA. NR 24 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 0736-4679 EI 1090-1280 J9 J EMERG MED JI J. Emerg. Med. PD AUG PY 2015 VL 49 IS 2 BP 183 EP 187 PG 5 WC Emergency Medicine SC Emergency Medicine GA CN7EV UT WOS:000358597800019 PM 26022937 ER PT J AU Probst, MA Kanzaria, HK Hoffman, JR Mower, WR Moheimani, RS Sun, BC Quigley, DD AF Probst, Marc A. Kanzaria, Hemal K. Hoffman, Jerome R. Mower, William R. Moheimani, Roya S. Sun, Benjamin C. Quigley, Denise D. TI EMERGENCY PHYSICIANS' PERCEPTIONS AND DECISION-MAKING PROCESSES REGARDING PATIENTS PRESENTING WITH PALPITATIONS SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE palpitations; emergency medicine; clinical decision-making; interviews ID MANAGEMENT; SYNCOPE; CARE AB Background: Palpitations are a common emergency department (ED) complaint, yet relatively little research exists on this topic from an emergency care perspective. Objectives: We sought to describe the perceptions and clinical decision-making processes of emergency physicians (EP) surrounding patients with palpitations. Methods: We conducted 21 semistructured interviews with a convenience sample of EPs. We recruited participants from academic and community practice settings from four regions of the United States. The transcribed interviews were analyzed using a combination of structural coding and grounded theory approaches with ATLAS.ti, a qualitative data analysis software program (version 7; Atlas.ti Scientific Software Development GmbH, Berlin, Germany). Results: EPs perceive palpitations to be a common but generally benign chief complaint. EPs' clinical approach to palpitations, with regards to testing, treatment, and ED management, can be classified as relating to one or more of the following themes: 1) risk stratification, 2) diagnostic categorization, 3) algorithmic management, and 4) case-specific gestalt. With regard to disposition decisions, four main themes emerged: 1) presence of a serious diagnosis, 2) perceived need for further cardiac testing/monitoring, 3) presence of key associated symptoms, 4) request of other physician or patient desire. The interrater reliability exercise yielded a Fleiss' kappa measure of 0.69, indicating substantial agreement between coders. Conclusion: EPs perceive palpitations to be a common but generally benign chief complaint. EPs rely on one or more of four main clinical approaches to manage these patients. These findings could help guide future efforts at developing risk-stratification tools and clinical algorithms for patients with palpitations. (C) 2015 Elsevier Inc. C1 [Probst, Marc A.; Kanzaria, Hemal K.; Hoffman, Jerome R.; Mower, William R.; Moheimani, Roya S.] Univ Calif Los Angeles, Sch Med, Dept Emergency Med, Los Angeles, CA USA. [Probst, Marc A.] Icahn Sch Med Mt Sinai, Dept Emergency Med, New York, NY 10029 USA. [Kanzaria, Hemal K.] W Los Angeles Vet Affairs Med Ctr, US Dept Vet Affairs, Los Angeles, CA 90073 USA. [Sun, Benjamin C.] Oregon Hlth & Sci Univ, Ctr Policy Res Emergency Med, Dept Emergency Med, Portland, OR 97201 USA. [Quigley, Denise D.] RAND Corp, Santa Monica, CA USA. RP Probst, MA (reprint author), Icahn Sch Med Mt Sinai, Dept Emergency Med, 3 East 101st St,2nd Floor, New York, NY 10029 USA. FU Robert Wood Johnson Foundation Clinical Scholars Program; National Heart, Lung, and Blood Institute of the National Institutes of Health [5K12 HL109005, R01 HL111033]; National Heart, Lung, and Blood Institute FX This work was supported by the Robert Wood Johnson Foundation Clinical Scholars Program (HKK) and by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number 5K12 HL109005 (MAP) and Award Number R01 HL111033 (BCS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Robert Wood Johnson Foundation. There are no conflicts of interest. The authors would like to thank all of the emergency physicians who generously offered their time to participate in these interviews. The authors would also like to thank the National Heart, Lung, and Blood Institute and the Robert Wood Johnson Foundation Clinical Scholars Program for their support. NR 22 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 EI 1090-1280 J9 J EMERG MED JI J. Emerg. Med. PD AUG PY 2015 VL 49 IS 2 BP 236 EP + DI 10.1016/j.jemermed.2015.02.013 PG 10 WC Emergency Medicine SC Emergency Medicine GA CN7EV UT WOS:000358597800029 PM 25943288 ER PT J AU Pelak, M Pettit, AR Terwiesch, C Gutierrez, JC Marcus, SC AF Pelak, Mary Pettit, Amy R. Terwiesch, Christian Gutierrez, Jennifer C. Marcus, Steven C. TI Rethinking primary care visits: how much can be eliminated, delegated or performed outside of the face-to-face visit? SO JOURNAL OF EVALUATION IN CLINICAL PRACTICE LA English DT Article DE face-to-face visits; patient-centred medical home; practice revision; primary care; routine practice; videotaping ID PRACTICE TRANSFORMATION; HEALTH-CARE; PHYSICIANS; QUALITY AB Rationale, aims and objectivesOffice visits represent the core component of primary care practice, but little is known about what percentage of primary care provider (PCP) visit time could be suitable for reassignment to another medical home team member or to a non-face-to-face modality (e.g. secure messaging) in order to optimize face-to-face PCP visit time. MethodWe videotaped 121 PCP office visits at four Veterans Health Administration Medical Centers and divided visits into discrete activity segments. Two physicians reviewed each visit recording and provided independent clinical judgments regarding which segments might be suitable for reassignment. We examined the activity category distribution of visit time rated as needing face-to-face time with a PCP. ResultsReviewers judged 53% of the 5398 minutes of rated visit time as suitable for reassignment to another team member or modality. The percentage of time rated as needing face-to-face PCP care varied greatly by activity category, from a high of 73.9% (for examining patients) to a low of 16.2% (for medication review). Rater agreement regarding tasks' suitability for reassignment varied across activity categories. ConclusionsThese data offer an example of how face-to-face PCP visit time might be optimized as practices seek to shift components of patient care to other team members and other modalities. Given variations in provider preferences and judgments, successful redesign efforts will need to involve stakeholders in decisions about how to best utilize medical home resources. C1 [Pelak, Mary; Terwiesch, Christian; Gutierrez, Jennifer C.; Marcus, Steven C.] Philadelphia Vet Affairs Med Ctr, CEPACT, Philadelphia, PA USA. [Terwiesch, Christian] Univ Penn, Wharton Sch & Prof Hlth Policy, Perelman Sch Med, Philadelphia, PA 19104 USA. [Marcus, Steven C.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. RP Marcus, SC (reprint author), Univ Penn, Sch Social Policy & Practice, 3701 Locust Walk, Philadelphia, PA 19104 USA. EM marcuss@upenn.edu FU VA Office of Patient Care Services FX Support: The VISN 4 Center for Evaluation of PACT Demonstration Laboratory is funded by the VA Office of Patient Care Services. NR 24 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1356-1294 EI 1365-2753 J9 J EVAL CLIN PRACT JI J. Eval. Clin. Pract. PD AUG PY 2015 VL 21 IS 4 BP 591 EP 596 DI 10.1111/jep.12341 PG 6 WC Health Care Sciences & Services; Medical Informatics; Medicine, General & Internal SC Health Care Sciences & Services; Medical Informatics; General & Internal Medicine GA CN8LX UT WOS:000358693200007 PM 25756943 ER PT J AU Hull, RL Baskin, DG AF Hull, Rebecca L. Baskin, Denis G. TI Histochemical Insights into Pancreatic Islet Biology SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Editorial Material C1 [Hull, Rebecca L.] VA Puget Sound Hlth Care Syst, Res & Dev Serv, Seattle, WA 98108 USA. [Hull, Rebecca L.; Baskin, Denis G.] Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. RP Hull, RL (reprint author), VA Puget Sound Hlth Care Syst, Res & Dev Serv, 1660 S Columbian Way,Mail Stop S-151, Seattle, WA 98108 USA. EM rhull@uw.edu NR 12 TC 1 Z9 1 U1 1 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0022-1554 EI 1551-5044 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD AUG PY 2015 VL 63 IS 8 SI SI BP 541 EP 542 DI 10.1369/0022155415586442 PG 2 WC Cell Biology SC Cell Biology GA CN7ES UT WOS:000358597500001 PM 26216132 ER PT J AU Baskin, DG AF Baskin, Denis G. TI A Historical Perspective on the Identification of Cell Types in Pancreatic Islets of Langerhans by Staining and Histochemical Techniques SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Review DE diabetes; beta cells; glucagon; immunocytochemistry; immunohistochemistry; insulin; islet cells; pancreas; staining; somatostatin ID HORMONE-PRODUCING CELLS; EMBRYONIC STEM-CELLS; ADULT HUMAN PANCREAS; GUINEA-PIG PANCREAS; NEURAL CREST ORIGIN; ALDEHYDE-FUCHSIN; BETA-CELL; B-CELL; ULTRASTRUCTURAL-LOCALIZATION; AMYLOID POLYPEPTIDE AB Before the middle of the previous century, cell types of the pancreatic islets of Langerhans were identified primarily on the basis of their color reactions with histological dyes. At that time, the chemical basis for the staining properties of islet cells in relation to the identity, chemistry and structure of their hormones was not fully understood. Nevertheless, the definitive islet cell types that secrete glucagon, insulin, and somatostatin (A, B, and D cells, respectively) could reliably be differentiated from each other with staining protocols that involved variations of one or more tinctorial techniques, such as the Mallory-Heidenhain azan trichrome, chromium hematoxylin and phloxine, aldehyde fuchsin, and silver impregnation methods, which were popularly used until supplanted by immunohistochemical techniques. Before antibody-based staining methods, the most bona fide histochemical techniques for the identification of islet B cells were based on the detection of sulfhydryl and disulfide groups of insulin. The application of the classical islet tinctorial staining methods for pathophysiological studies and physiological experiments was fundamental to our understanding of islet architecture and the physiological roles of A and B cells in glucose regulation and diabetes. C1 [Baskin, Denis G.] VA Puget Sound Hlth Care Syst, Res & Dev Serv, Seattle, WA 98108 USA. [Baskin, Denis G.] Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. RP Baskin, DG (reprint author), VA Puget Sound Hlth Care Syst, Res & Dev Serv, 1660 S Columbian Way,Mail Stop S-151, Seattle, WA 98108 USA. EM baskindg@uw.edu FU Office of Research and Development of the Department of Veterans Affairs; Cellular and Molecular Imaging Core of the University of Washington Diabetes Research Center from the NIH National Institute of Diabetes and Digestive and Kidney Diseases [P30 DK017047]; VA Senior Research Career Scientist award FX The author disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This material is based upon work supported by the Office of Research and Development of the Department of Veterans Affairs, and by the Cellular and Molecular Imaging Core of the University of Washington Diabetes Research Center (grant P30 DK017047 from the NIH National Institute of Diabetes and Digestive and Kidney Diseases). DGB is the recipient of a VA Senior Research Career Scientist award. NR 111 TC 0 Z9 0 U1 7 U2 17 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0022-1554 EI 1551-5044 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD AUG PY 2015 VL 63 IS 8 SI SI BP 543 EP 558 DI 10.1369/0022155415589119 PG 16 WC Cell Biology SC Cell Biology GA CN7ES UT WOS:000358597500002 PM 26216133 ER PT J AU Hull, RL Bogdani, M Nagy, N Johnson, PY Wight, TN AF Hull, Rebecca L. Bogdani, Marika Nagy, Nadine Johnson, Pamela Y. Wight, Thomas N. TI Hyaluronan: A Mediator of Islet Dysfunction and Destruction in Diabetes? SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE diabetes; extracellular matrix; islet; hyaluronan; hyaladherins ID STIMULATED-INSULIN-SECRETION; ALPHA-TRYPSIN INHIBITOR; HUMAN PANCREATIC-ISLETS; SMOOTH-MUSCLE-CELLS; EXTRACELLULAR-MATRIX; BASEMENT-MEMBRANE; BETA-CELLS; BINDING-PROTEINS; POLYCYTIDYLIC ACID; CROSS-LINKING AB Hyaluronan (HA) is an extracellular matrix (ECM) component that is present in mouse and human islet ECM. HA is localized in peri-islet and intra-islet regions adjacent to microvessels. HA normally exists in a high molecular weight form, which is anti-inflammatory. However, under inflammatory conditions, HA is degraded into fragments that are proinflammatory. HA accumulates in islets of human subjects with recent onset type 1 diabetes (T1D), and is associated with myeloid and lymphocytic islet infiltration, suggesting a possible role for HA in insulitis. A similar accumulation of HA, in amount and location, occurs in non-obese diabetic (NOD) and DORmO mouse models of T1D. Furthermore, HA accumulates in follicular germinal centers and in T-cell areas in lymph nodes and spleen in both human and mouse models of T1D, as compared with control tissues. Whether HA accumulates in islets in type 2 diabetes (T2D) or models thereof has not been previously described. Here we show evidence that HA accumulates in a mouse model of islet amyloid deposition, a well-known component of islet pathology in T2D. In summary, islet HA accumulation is a feature of both T1D and a model of T2D, and may represent a novel inflammatory mediator of islet pathology. C1 [Hull, Rebecca L.] VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Hull, Rebecca L.] Univ Washington, Seattle, WA 98108 USA. [Wight, Thomas N.] Univ Washington, Dept Pathol, Seattle, WA 98108 USA. [Bogdani, Marika; Nagy, Nadine; Johnson, Pamela Y.; Wight, Thomas N.] Benaroya Res Inst Virginia Mason, Matrix Biol Program, Seattle, WA USA. RP Hull, RL (reprint author), VA Puget Sound Hlth Care Syst 151, 1660 S Columbian Way, Seattle, WA 98108 USA. EM rhull@uw.edu OI Hull, Rebecca/0000-0001-9690-4087 FU Department of Veterans Affairs; VA Puget Sound Health Care System (Seattle, WA, USA); National Institutes of Health [DK088082, DK017047, U01 AI101990, U01 AI101984]; Juvenile Diabetes Research Foundation [nPOD 25-2010-648]; Deutsche Forschungsgemeinschaft [NA 965/2-1] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Department of Veterans Affairs, VA Puget Sound Health Care System (Seattle, WA, USA), National Institutes of Health grants DK088082 (RLH); DK017047 (University of Washington Diabetes Research Center); and U01 AI101990 Pilot Project, U01 AI101984, and the Juvenile Diabetes Research Foundation [nPOD 25-2010-648 (TNW)]. NN was supported by research grant NA 965/2-1 from the Deutsche Forschungsgemeinschaft. NR 91 TC 0 Z9 0 U1 2 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0022-1554 EI 1551-5044 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD AUG PY 2015 VL 63 IS 8 SI SI BP 592 EP 603 DI 10.1369/0022155415576542 PG 12 WC Cell Biology SC Cell Biology GA CN7ES UT WOS:000358597500005 PM 26216136 ER PT J AU Bonner-Weir, S Sullivan, BA Weir, GC AF Bonner-Weir, Susan Sullivan, Brooke A. Weir, Gordon C. TI Human Islet Morphology Revisited: Human and Rodent Islets Are Not So Different After All SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE human islets; islet composition; islet architecture; mantle-core ID CELLULAR PERFUSION; BETA-CELL; INCRETIN THERAPY; LANGERHANS; PANCREAS; RAT; SOMATOSTATIN; ARCHITECTURE; EXPRESSION; EXPANSION AB There has been great interest in understanding how human islets differ from rodent islets. Three major issues about human islet morphology have remained controversial over recent decades: 1) the proportion of the islet made up of -cells; 2) whether islet cell types have a non-random mantle-core pattern, as seen in rodents, or are randomly scattered throughout the islet; 3) the relation of the different cell types to the blood vessels within the islet, which has implications for intraislet function. We re-examined these issues on immunostained sections of non-diabetic adult human pancreas. The composition of the islets can vary by the analysis method (number vs volume) and by the sampling of islets by size. The majority of adult human islets have clear, non-random clustering of -cells and blood vessels that penetrate into the -cell cores. We conclude that although there is far more variability in islet composition both within each human pancreas and among different human pancreas than in rodent pancreas, the islet architecture is not so different between the species. The intrapancreatic variability raises important questions about how islets evolve and function throughout life and how this might relate to the pathogenesis of diabetes. C1 [Bonner-Weir, Susan; Sullivan, Brooke A.; Weir, Gordon C.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Bonner-Weir, S (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM susan.bonner-weir@joslin.harvard.edu OI Bonner-Weir, Susan/0000-0003-4682-0656 FU National Institutes of Health [NIH R01 DK093909, P30 DK036836, NCRR ICR U4ZRR016606]; Diabetes Research and Wellness Foundation FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This current study was supported by grants from the National Institutes of Health (NIH R01 DK093909 (SBW), P30 DK036836 Joslin Diabetes Research Center (DRC), NCRR ICR U4ZRR016606 (GCW), the Diabetes Research and Wellness Foundation and an important group of private donors. NR 26 TC 11 Z9 11 U1 3 U2 10 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0022-1554 EI 1551-5044 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD AUG PY 2015 VL 63 IS 8 SI SI BP 604 EP 612 DI 10.1369/0022155415570969 PG 9 WC Cell Biology SC Cell Biology GA CN7ES UT WOS:000358597500006 PM 25604813 ER PT J AU Brissova, M Shostak, A Fligner, CL Revetta, FL Washington, MK Powers, AC Hull, RL AF Brissova, Marcela Shostak, Alena Fligner, Corinne L. Revetta, Frank L. Washington, Mary K. Powers, Alvin C. Hull, Rebecca L. TI Human Islets Have Fewer Blood Vessels than Mouse Islets and the Density of Islet Vascular Structures Is Increased in Type 2 Diabetes SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE amyloid; diabetes; islet; pancreas; vasculature ID GROWTH FACTOR-A; HUMAN PANCREATIC-ISLETS; BETA-CELL APOPTOSIS; ENDOTHELIAL-CELL; AMYLOID POLYPEPTIDE; INSULIN-SECRETION; BASEMENT-MEMBRANE; GLUCOSE-TRANSPORTER; ELECTRON-MICROSCOPY; ENDOCRINE PANCREAS AB Human and rodent islets differ substantially in several features, including architecture, cell composition, gene expression and some aspects of insulin secretion. Mouse pancreatic islets are highly vascularized with interactions between islet endothelial and endocrine cells being important for islet cell differentiation and function. To determine whether human islets have a similar high degree of vascularization and whether this is altered with diabetes, we examined the vascularization of islets from normal human subjects, subjects with type 2 diabetes (T2D), and normal mice. Using an integrated morphometry approach to quantify intra-islet capillary density in human and mouse pancreatic sections, we found that human islets have five-fold fewer vessels per islet area than mouse islets. Islets in pancreatic sections from T2D subjects showed capillary thickening, some capillary fragmentation and had increased vessel density as compared with non-diabetic controls. These changes in islet vasculature in T2D islets appeared to be associated with amyloid deposition, which was noted in islets from 8/9 T2D subjects (and occupied 14% +/- 4% of islet area), especially around the intra-islet capillaries. The physiological implications of the differences in the angioarchitecture of mouse and human islets are not known. Islet vascular changes in T2D may exacerbate cell/islet dysfunction and cell loss. C1 [Brissova, Marcela; Shostak, Alena; Powers, Alvin C.] Vanderbilt Univ, Dept Med, Nashville Med Ctr, Div Diabet Endocrinol & Metab, Nashville, TN USA. [Revetta, Frank L.; Washington, Mary K.] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. [Powers, Alvin C.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Med Ctr, Nashville, TN 37232 USA. [Powers, Alvin C.] VA Tennessee Valley Healthcare Syst, Nashville, TN USA. [Fligner, Corinne L.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Hull, Rebecca L.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. [Hull, Rebecca L.] Univ Washington, Seattle, WA 98195 USA. RP Hull, RL (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM rhull@uw.edu OI Hull, Rebecca/0000-0001-9690-4087 FU Department of Veterans Affairs; VA Tennessee Valley and Puget Sound Health Care Systems; Department of Veterans Affairs (Merit Review); NIH [DK69603, DK88082, DK89572, DK89538]; Vanderbilt Diabetes Research and Training Center [DK20593]; University of Washington Diabetes Research Center (Cellular and Molecular Imaging Core) [DK17047] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Department of Veterans Affairs, VA Tennessee Valley and Puget Sound Health Care Systems and grant support from the Department of Veterans Affairs (Merit Review), the NIH (DK69603, DK88082, DK89572, DK89538), the Vanderbilt Diabetes Research and Training Center (DK20593) and the University of Washington Diabetes Research Center (Cellular and Molecular Imaging Core; DK17047). NR 57 TC 7 Z9 7 U1 0 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0022-1554 EI 1551-5044 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD AUG PY 2015 VL 63 IS 8 SI SI BP 637 EP 645 DI 10.1369/0022155415573324 PG 9 WC Cell Biology SC Cell Biology GA CN7ES UT WOS:000358597500009 PM 26216139 ER PT J AU Meier, DT Entrup, L Templin, AT Hogan, MF Samarasekera, T Zraika, S Boyko, EJ Kahn, SE AF Meier, Daniel T. Entrup, Leon Templin, Andrew T. Hogan, Meghan F. Samarasekera, Thanya Zraika, Sakeneh Boyko, Edward J. Kahn, Steven E. TI Determination of Optimal Sample Size for Quantification of beta-Cell Area, Amyloid Area and beta-Cell Apoptosis in Isolated Islets SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE amyloid; apoptosis; beta cell; histology; insulin; islet isolation; immunohistochemistry; pancreatic islet; staining ID DIABETES-MELLITUS; FIBRIL FORMATION; TRANSGENIC MICE; POLYPEPTIDE; GLUCOSE; PANCREAS; HYPERGLYCEMIA; EXPRESSION; RATHER; TYPE-1 AB Culture of isolated rodent islets is widely used in diabetes research to assess different endpoints, including outcomes requiring histochemical staining. As islet yields during isolation are limited, we determined the number of islets required to obtain reliable data by histology. We found that mean values for insulin-positive -cell area/islet area, thioflavin S-positive amyloid area/islet area and -cell apoptosis do not vary markedly when more than 30 islets are examined. Measurement variability declines as more islets are quantified, so that the variability of the coefficient of variation (CV) in human islet amyloid polypeptide (hIAPP) transgenic islets for -cell area/islet area, amyloid area/islet area and -cell apoptosis are 13.20% +/- 1.52%, 10.03% +/- 1.76% and 6.78% +/- 1.53%, respectively (non-transgenic: 7.65% +/- 1.17% -cell area/islet area and 8.93% +/- 1.56% -cell apoptosis). Increasing the number of islets beyond 30 had marginal effects on the CV. Using 30 islets, 6 hIAPP-transgenic preparations are required to detect treatment effects of 14% for -cell area/islet area, 30% for amyloid area/islet area and 23% for -cell apoptosis (non-transgenic: 9% for -cell area/islet area and 45% for -cell apoptosis). This information will be of value in the design of studies using isolated islets to examine cells and islet amyloid. C1 [Meier, Daniel T.; Entrup, Leon; Templin, Andrew T.; Hogan, Meghan F.; Samarasekera, Thanya; Zraika, Sakeneh; Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Meier, Daniel T.; Entrup, Leon; Templin, Andrew T.; Hogan, Meghan F.; Samarasekera, Thanya; Zraika, Sakeneh; Boyko, Edward J.; Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Boyko, Edward J.] VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Boyko, Edward J.] VA Puget Sound Hlth Care Syst, Div Gen Internal Med, Seattle, WA USA. RP Meier, DT (reprint author), VA Puget Sound Hlth Care Syst 151, 1660 S Columbian Way, Seattle, WA 98108 USA. EM meierdan@uw.edu FU Department of Veterans Affairs [BX001060]; NIH [DK-007247, DK-080945, DK-017047]; Swiss National Science Foundation Fellowship; Dick and Julia McAbee Endowed Fellowship in Diabetes Research from the University of Washington; American Diabetes Association Mentor-Based Fellowship FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Department of Veterans Affairs grant BX001060 and NIH grants DK-007247, DK-080945 and DK-017047. DTM was supported by a Swiss National Science Foundation Fellowship and the Dick and Julia McAbee Endowed Fellowship in Diabetes Research from the University of Washington. TS and ATT were supported by an American Diabetes Association Mentor-Based Fellowship. NR 32 TC 7 Z9 7 U1 1 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0022-1554 EI 1551-5044 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD AUG PY 2015 VL 63 IS 8 SI SI BP 663 EP 673 DI 10.1369/0022155415585995 PG 11 WC Cell Biology SC Cell Biology GA CN7ES UT WOS:000358597500011 PM 26216141 ER PT J AU Miller, DM Schapira, MM Visotcky, AM Laud, P Arora, VM Kordus, A Whittle, J Singh, S Fletcher, KE AF Miller, Donna M. Schapira, Marilyn M. Visotcky, Alexis M. Laud, Purushottam Arora, Vineet M. Kordus, Andrew Whittle, Jeff Singh, Siddhartha Fletcher, Kathlyn E. TI Changes in written sign-out composition across hospitalization SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID HANDOFFS; COMMUNICATION; CHECKLIST; WORKLOAD; INTERNS; CARE AB BACKGROUNDInaccurate or incomplete information in the written portion of the patient handoff, or sign-out, may be associated with adverse events in hospitalized patients. Little is known about what information providers actually include in written sign-out documents and how sign-outs change over time. OBJECTIVES(1) Provide a descriptive analysis of initial and subsequent hospital day-written sign-out content, and (2) evaluate the relationship between team workload and sign-out composition. DESIGNRetrospective review of sign-out documents from a larger observational study of general medicine patients admitted to housestaff and hospitalist teams at 3 hospitals. MAIN MEASURESThe presence of 13 components of a high-quality sign-out. We performed descriptive analyses and compared initial and subsequent day sign-outs for content. KEY RESULTSWe reviewed 200 patient hospitalizations (200 initial handoffs, 580 subsequent day handoffs). Initial sign-out entries contained a mean of 7.54 (standard deviation: 2.27) key sign-out components. Subsequent day sign-outs contained a higher percentage of certain key elements but had more vague language. The number of elements present in the sign-out was reduced as patient census increased (r=-0.295, P<0.01). CONCLUSIONSSign-out composition changes over time, and is associated with workload. Future interventions to improve quality should take these factors into consideration. Journal of Hospital Medicine 2015;10:534-536. (c) 2015 Society of Hospital Medicine. C1 [Miller, Donna M.] Mayo Clin, Sch Med, Dept Internal Med, Div Hosp Internal Med, Rochester, MN USA. [Schapira, Marilyn M.] Univ Penn, Dept Internal Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Schapira, Marilyn M.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Visotcky, Alexis M.; Laud, Purushottam] Med Coll Wisconsin, Dept Biostat, Milwaukee, WI 53295 USA. [Arora, Vineet M.] Univ Chicago, Dept Med, Gen Internal Med Sect, Chicago, IL 60637 USA. [Kordus, Andrew] Nova SE Univ, Coll Osteopath Med, Davie, FL USA. [Whittle, Jeff; Singh, Siddhartha; Fletcher, Kathlyn E.] Clement J Zablocki VAMC, Dept Internal Med, Milwaukee, WI USA. [Whittle, Jeff; Singh, Siddhartha; Fletcher, Kathlyn E.] Med Coll Wisconsin, Milwaukee, WI 53295 USA. RP Fletcher, KE (reprint author), Med Coll Wisconsin, Clement J Zablocki VAMC, 5000 W Natl Ave, Milwaukee, WI 53295 USA. EM kfletche@mcw.edu OI Arora, Vineet/0000-0002-4745-7599 FU Veterans Affairs Health Services Research & Development grant IIR [07-201] FX This work was supported by Veterans Affairs Health Services Research & Development grant IIR #07-201. The authors report no conflicts of interest. NR 15 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD AUG PY 2015 VL 10 IS 8 BP 534 EP 536 DI 10.1002/jhm.2390 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA CN8LZ UT WOS:000358693600010 PM 26061434 ER PT J AU Sheehy, AM Kolehmainen, C Carnes, M AF Sheehy, Ann M. Kolehmainen, Christine Carnes, Molly TI We specialize in change leadership: A call for hospitalists to lead the quest for workforce gender equity SO JOURNAL OF HOSPITAL MEDICINE LA English DT Editorial Material ID ACADEMIC MEDICINE; WOMEN; METAANALYSIS; FACULTY; NEGOTIATIONS; ADVANCEMENT; PHYSICIANS; EMOTION; BIAS C1 [Sheehy, Ann M.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Div Hosp Med, Madison, WI 53705 USA. [Kolehmainen, Christine] William S Middleton Mem Vet Adm Med Ctr, Dept Med, Madison, WI USA. [Kolehmainen, Christine] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53705 USA. [Carnes, Molly] Univ Wisconsin, Women Sci & Engn Leadership Inst, Ctr Womens Hlth Res, Dept Med, Madison, WI 53705 USA. [Carnes, Molly] Univ Wisconsin, Women Sci & Engn Leadership Inst, Ctr Womens Hlth Res, Dept Psychiat, Madison, WI 53705 USA. [Carnes, Molly] Univ Wisconsin, Women Sci & Engn Leadership Inst, Ctr Womens Hlth Res, Dept Ind & Syst Engn, Madison, WI 53705 USA. RP Sheehy, AM (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Div Hosp Med, 1685 Highland Ave,MFCB 3126, Madison, WI 53705 USA. EM asr@medicine.wisc.edu NR 33 TC 0 Z9 0 U1 3 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD AUG PY 2015 VL 10 IS 8 BP 551 EP 552 DI 10.1002/jhm.2399 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CN8LZ UT WOS:000358693600014 PM 26122268 ER PT J AU Sharma, RK Breu, AC AF Sharma, Rashmi K. Breu, Anthony C. TI Making progress with code status documentation SO JOURNAL OF HOSPITAL MEDICINE LA English DT Editorial Material ID HOSPITALIZED-PATIENTS; STATUS DISCUSSIONS; CARE; RESUSCITATION; PREFERENCES; RESIDENTS C1 [Sharma, Rashmi K.] Northwestern Univ, Div Hosp Med, Chicago, IL 60611 USA. [Breu, Anthony C.] VA Boston Healthcare Syst, Dept Med Serv, West Roxbury, MA USA. RP Sharma, RK (reprint author), Northwestern Univ, Div Hosp Med, 211 E Ontario St,07-734, Chicago, IL 60611 USA. EM rasharma@nmh.org FU NICHD NIH HHS [K12 HD055884] NR 10 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD AUG PY 2015 VL 10 IS 8 BP 553 EP 554 DI 10.1002/jhm.2349 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CN8LZ UT WOS:000358693600015 PM 25873559 ER PT J AU Polewski, MA Burhans, MS Zhao, MH Colman, RJ Shanmuganayagam, D Lindstrom, MJ Ntambi, JM Anderson, RM AF Polewski, Michael A. Burhans, Maggie S. Zhao, Minghui Colman, Ricki J. Shanmuganayagam, Dhanansayan Lindstrom, Mary J. Ntambi, James M. Anderson, Rozalyn M. TI Plasma diacylglycerol composition is a biomarker of metabolic syndrome onset in rhesus monkeys SO JOURNAL OF LIPID RESEARCH LA English DT Article DE lipids; lipoproteins; insulin; obesity; adipose tissue; cholesteryl esters; free fatty acids; phospholipids; triacylglycerols; adiponectin ID FATTY-ACID-COMPOSITION; TYPE-2 DIABETES-MELLITUS; LINKING ADIPOSE-TISSUE; CARDIOVASCULAR-DISEASE; DIETARY RESTRICTION; BODY-COMPOSITION; INFLAMMATION; ADIPONECTIN; OBESITY; SERUM AB Metabolic syndrome is linked with obesity and is often first identified clinically by elevated BMI and elevated levels of fasting blood glucose that are generally secondary to insulin resistance. Using the highly translatable rhesus monkey (Macaca mulatta) model, we asked if metabolic syndrome risk could be identified earlier. The study involved 16 overweight but healthy, euglycemic monkeys, one-half of which spontaneously developed metabolic syndrome over the course of 2 years while the other half remained healthy. We conducted a series of biometric and plasma measures focusing on adiposity, lipid metabolism, and adipose tissue-derived hormones, which led to a diagnosis of metabolic syndrome in the insulin-resistant animals. Plasma fatty acid composition was determined by gas chromatography for cholesteryl ester, FFA, diacylglycerol (DAG), phospholipid, and triacylglycerol lipid classes; plasma lipoprotein profiles were generated by NMR; and circulating levels of adipose-derived signaling peptides were determined by ELISA. We identified biomarker models including a DAG model, two lipoprotein models, and a multiterm model that includes the adipose-derived peptide adiponectin. Correlations among circulating lipids and lipoproteins revealed shifts in lipid metabolism during disease development.Jlr We propose that lipid profiling may be valuable for early metabolic syndrome detection in a clinical setting. C1 [Polewski, Michael A.; Burhans, Maggie S.; Anderson, Rozalyn M.] Univ Wisconsin, Dept Med, Madison, WI 53706 USA. [Zhao, Minghui; Ntambi, James M.] Univ Wisconsin, Dept Biochem, Madison, WI 53705 USA. [Colman, Ricki J.; Shanmuganayagam, Dhanansayan] Univ Wisconsin, Natl Primate Res Ctr, Madison, WI USA. [Lindstrom, Mary J.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA. [Ntambi, James M.] Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA. [Anderson, Rozalyn M.] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. RP Anderson, RM (reprint author), Univ Wisconsin, Dept Med, Madison, WI 53706 USA. EM rmanderson@medicine.wisc.edu FU National Institutes of Health/National Institute on Aging [AG037000, AG11915, AG040178]; National Institutes of Health/National Center for Research Resources/Clinical and Translational Science Award [UL1RR025011]; Research Facilities Improvement Program [RR15459-01, RR020141-01]; [P51OD011106] FX This work was supported by National Institutes of Health/National Institute on Aging Grants AG037000, AG11915, and AG040178, and by National Institutes of Health/National Center for Research Resources/Clinical and Translational Science Award UL1RR025011. The study was conducted with the use of resources and facilities at the William S. Middleton Memorial Veterans Hospital, Madison, WI. The Wisconsin National Primate Research Center is supported by P51OD011106 and Research Facilities Improvement Program Grants RR15459-01 and RR020141-01. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No potential conflicts of interest relevant to this article are reported. NR 47 TC 2 Z9 2 U1 3 U2 14 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 EI 1539-7262 J9 J LIPID RES JI J. Lipid Res. PD AUG PY 2015 VL 56 IS 8 BP 1461 EP 1470 DI 10.1194/jlr.M057562 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CN8CT UT WOS:000358666000008 PM 26063458 ER PT J AU Zhang, TJ Barclay, L Walensky, LD Saghatelian, A AF Zhang, Tejia Barclay, Lauren Walensky, Loren D. Saghatelian, Alan TI Regulation of mitochondrial ceramide distribution by members of the BCL-2 family SO JOURNAL OF LIPID RESEARCH LA English DT Article DE apoptosis; ceramides; lipidomics; mass spectrometry; sphingolipids ID TANDEM MASS-SPECTROMETRY; ELECTROSPRAY-IONIZATION; SERINE PALMITOYLTRANSFERASE; CHROMOSOMAL BREAKPOINT; BH3-ONLY PROTEINS; CELL-SURVIVAL; ESI-MS/MS; APOPTOSIS; BAK; DEATH AB Apoptosis is an intricately regulated cellular process that proceeds through different cell type-and signal-dependent pathways. In the mitochondrial apoptotic program, mitochondrial outer membrane permeabilization by BCL-2 proteins leads to the release of apoptogenic factors, caspase activation, and cell death. In addition to protein components of the mitochondrial apoptotic machinery, an interesting role for lipids and lipid metabolism in BCL-2 family-regulated apoptosis is also emerging. We used a comparative lipidomics approach to uncover alterations in lipid profile in the absence of the proapoptotic proteins BAX and BAK in mouse embryonic fibroblasts (MEFs). We detected over 1,000 ions in these experiments and found changes in an ion with an m/z of 534.49. Structural elucidation of this ion through tandem mass spectrometry revealed that this molecule is a ceramide with a 16-carbon N-acyl chain and sphingadiene backbone (d18:2/16:0 ceramide). Targeted LC/MS analysis revealed elevated levels of additional sphingadiene-containing ceramides (d18:2-Cers) in BAX, BAK-double knockout MEFs. Elevated d18: 2-Cers are also found in immortalized baby mouse kidney epithelial cells lacking BAX and BAK.Jlr These results support the existence of a distinct biochemical pathway for regulating ceramides with different backbone structures and suggest that sphingadiene-containing ceramides may have functions that are distinct from the more common sphingosine-containing species C1 [Zhang, Tejia; Saghatelian, Alan] Salk Inst Biol Studies, Helmsley Ctr Genom Med, Clayton Fdn Labs Peptide Biol, San Diego, CA 92037 USA. [Barclay, Lauren; Walensky, Loren D.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. Childrens Hosp Boston, Boston, MA 02215 USA. [Walensky, Loren D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Linde Program Canc Chem Biol, Boston, MA 02215 USA. RP Saghatelian, A (reprint author), Salk Inst Biol Studies, Helmsley Ctr Genom Med, Clayton Fdn Labs Peptide Biol, San Diego, CA 92037 USA. EM asaghatelian@salk.edu FU Eli Lilly Fellowship; Burroughs Wellcome Fund Award; Searle Scholars Award; NIH [5R01CA050239] FX This research is supported by an Eli Lilly Fellowship (T.Z.), a Burroughs Wellcome Fund Award (A.S.), a Searle Scholars Award (A.S.), and NIH grant 5R01CA050239 (L.D.W.). NR 60 TC 3 Z9 3 U1 2 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 EI 1539-7262 J9 J LIPID RES JI J. Lipid Res. PD AUG PY 2015 VL 56 IS 8 BP 1501 EP 1510 DI 10.1194/jlr.M058750 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CN8CT UT WOS:000358666000012 PM 26059977 ER PT J AU Stivaros, SM Stemmer-Rachamimov, AO Alston, R Plotkin, SR Nadol, JB Quesnel, A O'Malley, J Whitfield, GA McCabe, MG Freeman, SR Lloyd, SK Wright, NB Kilday, JP Kamaly-Asl, ID Mills, SJ Rutherford, SA King, AT Evans, DG AF Stivaros, Stavros M. Stemmer-Rachamimov, Anat O. Alston, Robert Plotkin, Scott R. Nadol, Joseph B. Quesnel, Alicia O'Malley, Jennifer Whitfield, Gillian A. McCabe, Martin G. Freeman, Simon R. Lloyd, Simon K. Wright, Neville B. Kilday, John-Paul Kamaly-Asl, Ian D. Mills, Samantha J. Rutherford, Scott A. King, Andrew T. Evans, D. Gareth TI Multiple synchronous sites of origin of vestibular schwannomas in neurofibromatosis Type 2 SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID STEREOTACTIC RADIOSURGERY; HEARING PRESERVATION; ACOUSTIC NEUROMAS; MANAGEMENT; NERVE; NF2; DIAGNOSIS AB Background Neurofibromatosis Type 2 (NF2) is a dominantly inherited tumour syndrome with a phenotype which includes bilateral vestibular (eighth cranial nerve) schwannomas. Conventional thinking suggests that these tumours originate at a single point along the superior division of the eighth nerve. Methods High resolution MRI was performed in children genetically proven to have NF2. The superior vestibular nerve (SVN) and inferior vestibular nerve (IVN) were visualised along their course with points of tumour origin calculated as a percentage relative to the length of the nerve. Results Out of 41 patients assessed, 7 patients had no identifiable eighth cranial nerve disease. In 16 patients there was complete filling of the internal auditory meatus by a tumour mass such that its specific neural origin could not be determined. In the remaining 18 cases, 86 discrete separate foci of tumour origin on the SVN or IVN could be identified including 23 tumours on the right SVN, 26 tumours on the right IVN, 18 tumours on the left SVN and 19 tumours on the left IVN. Discussion This study, examining the origins of vestibular schwannomas in NF2, refutes their origin as being from a single site on the transition zone of the superior division of the vestibular nerve. We hypothesise a relationship between the number of tumour foci, tumour biology and aggressiveness of disease. The development of targeted drug therapies in addition to bevacizumab are therefore essential to improve prognosis and quality of life in patients with NF2 given the shortcomings of surgery and radiation treatments when dealing with the multifocality of the disease. C1 [Stivaros, Stavros M.; Wright, Neville B.] Cent Manchester Univ Hosp NHS Fdn Trust, Royal Manchester Childrens Hosp, Acad Unit Paediat Radiol, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Stivaros, Stavros M.] Univ Manchester, Inst Populat Hlth, Ctr Imaging Sci, Manchester, Lancs, England. [Stivaros, Stavros M.; Kilday, John-Paul; Kamaly-Asl, Ian D.] Royal Manchester Childrens Hosp, Childrens Brain Tumour Res Network, Manchester M13 9WL, Lancs, England. [Stemmer-Rachamimov, Anat O.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Stemmer-Rachamimov, Anat O.; Plotkin, Scott R.] Harvard Univ, Sch Med, Boston, MA USA. [Alston, Robert] Univ Manchester, Inst Populat Hlth, Ctr Epidemiol, NDEC, Manchester, Lancs, England. [Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Nadol, Joseph B.; Quesnel, Alicia; O'Malley, Jennifer] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Whitfield, Gillian A.] Christie NHS Fdn Trust, Radiotherapy Related Res, Manchester, Lancs, England. [McCabe, Martin G.] Univ Manchester, Inst Canc Sci, Ctr Paediat Teenage & Young Adult Canc, Manchester, Lancs, England. [Freeman, Simon R.; Lloyd, Simon K.] Cent Manchester Univ Hosp NHS Fdn Trust, Dept Otolaryngol, Manchester Acad Hlth Sci Ctr, Manchester Royal Infirm, Manchester, Lancs, England. [Kamaly-Asl, Ian D.] Cent Manchester Univ Hosp NHS Fdn Trust, Dept Paediat Neurosurg, Royal Manchester Childrens Hosp, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Mills, Samantha J.] Salford NHS Fdn Trust Hosp, Dept Neuroradiol, Salford, Greater Manches, England. [Rutherford, Scott A.; King, Andrew T.] Salford Royal Hosp, Dept Neurosurg, Salford, Greater Manches, England. [Evans, D. Gareth] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, St Marys Hosp, Dept Genom Med, Manchester, Lancs, England. RP Stivaros, SM (reprint author), Royal Manchester Childrens Hosp, Acad Dept Paediat Radiol, Childrens XRay, Oxford Rd, Manchester M13 9WL, Lancs, England. EM Stavros.stivaros@manchester.ac.uk RI McCabe, Martin/P-5896-2015; OI McCabe, Martin/0000-0002-5138-0707; Whitfield, Gillian/0000-0003-4886-4329; King, Andrew/0000-0002-6546-7248; Evans, Gareth/0000-0002-8482-5784 FU National Institute for Health Research (NIHR) [NIHR/CS/010/021] FX National Institute for Health Research (NIHR) and facilitated by the Manchester Biomedical Research Centre and the NIHR Greater Manchester: Clinical Research Network. SMS funded by NIHR under award number NIHR/CS/010/021. NR 24 TC 6 Z9 6 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 EI 1468-6244 J9 J MED GENET JI J. Med. Genet. PD AUG PY 2015 VL 52 IS 8 BP 557 EP 562 DI 10.1136/jmedgenet-2015-103050 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA CN5BG UT WOS:000358443800008 PM 26104281 ER PT J AU Bier, JB Finger, AS Bier, BA Johnson, TA Coyle, MG AF Bier, J. B. Finger, A. S. Bier, B. A. Johnson, T. A. Coyle, M. G. TI Growth and developmental outcome of infants with in-utero exposure to methadone vs buprenorphine SO JOURNAL OF PERINATOLOGY LA English DT Article ID NEONATAL ABSTINENCE SYNDROME; WOMEN; MAINTENANCE; PERFORMANCE; PREGNANCY; HEALTH AB OBJECTIVE: To compare early growth and developmental outcome of infants with in-utero exposure to low-dose methadone (<100 mg per day), high-dose methadone (>= 100 mg per day) and buprenorphine. STUDY DESIGN: A retrospective review of infants with in-utero methadone and buprenorphine exposure who were evaluated at the Southcoast Developmental Pediatric clinic in New Bedford, MA, USA was completed. Growth data and developmental testing results during infancy were compared among the groups. RESULT: Infants in the high-dose methadone group had lower head circumference z scores and a lower mean score on the Alberta Infant Motor Scale (AIMS). Regression results confirmed an association between methadone dose and head circumference z score and AIMS score. CONCLUSION: Exposure to maternal methadone dose in excess of 100 mg is associated with a reduction in infant head circumference when compared with buprenorphine or lower dose methadone, and may have a negative impact on motor skill development during early infancy. C1 [Bier, J. B.] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Gen Pediat, Boston, MA USA. [Finger, A. S.] Harvard Univ, Sch Med, Dept Orthoped Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Bier, B. A.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. [Johnson, T. A.; Coyle, M. G.] St Lukes Hosp, Dept Phys Med, New Bedford, MA USA. [Coyle, M. G.] Brown Univ, Warren Alpert Med Sch, Women & Infants Hosp, Dept Pediat, Providence, RI 02912 USA. RP Bier, JB (reprint author), Boston Childrens Hosp, Complex Care Serv, 300 Longwood Ave, Boston, MA 02115 USA. EM jo-ann.bier@childrens.harvard.edu NR 22 TC 2 Z9 2 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0743-8346 EI 1476-5543 J9 J PERINATOL JI J. Perinatol. PD AUG PY 2015 VL 35 IS 8 BP 656 EP 659 DI 10.1038/jp.2015.22 PG 4 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA CN8IQ UT WOS:000358684100024 PM 25836317 ER PT J AU Stewart, PA Hyman, SL Schmidt, BL Macklin, EA Reynolds, A Johnson, CR James, SJ Manning-Courtney, P AF Stewart, Patricia A. Hyman, Susan L. Schmidt, Brianne L. Macklin, Eric A. Reynolds, Ann Johnson, Cynthia R. James, S. Jill Manning-Courtney, Patricia TI Dietary Supplementation in Children with Autism Spectrum Disorders: Common, Insufficient, and Excessive SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS LA English DT Article DE Autism; Nutrient intake; Dietary supplement use; Nutrient sufficiency/excess; Gluten-free/casein-free diet ID EFFICACY; ACID AB Background Little is known about the effect on dietary adequacy of supplements given to children with autism spectrum disorder (ASD). Objective This cross-sectional study examines dietary supplement use and micronutrient intake in children with ASD. Design Three-day diet/supplement records and use of a gluten/casein-free diet (GFCF) were documented. Estimates of usual intake of micronutrients from food and supplements were compared with the Dietary Reference Intakes. Participants Children aged 2 to 11 years (N = 288) with ASD from five Autism Treatment Network sites from 2009-2011. Main outcome measures Percentage of children meeting or exceeding upper limits of micronutrient intake with or without supplements and relative to GFCF diet status. Statistical analysis Micronutrient intake from food and supplements was compared by Spearman rank correlation. Usual intake was estimated by the National Cancer Institute method adjusted for age, sex, supplement use, and GFCF diet. Adequacy of intake was compared between supplement use status and between food and total intake in supplement users relative to Dietary Reference Intakes limits. Results Dietary supplements, especially multivitamin/minerals, were used by 56% of children with ASD. The most common micronutrient deficits were not corrected (vitamin D, calcium, potassium, pantothenic acid, and choline) by supplements. Almost one-third of children remained deficient for vitamin D and up to 54% for calcium. Children receiving GFCF diets had similar micronutrient intake but were more likely to use supplements (78% vs 56%; P=0.01). Supplementation led to excess vitamin A, folate, and zinc intake across the sample, vitamin C, and copper among children aged 2 to 3 years, and manganese and copper for children aged 4 to 8 years. Conclusions Few children with ASD need most of the micronutrients they are commonly given as supplements, which often leads to excess intake. Even when supplements are used, careful attention should be given to adequacy of vitamin D and calcium intake. C1 [Stewart, Patricia A.; Hyman, Susan L.] Univ Rochester, Med Ctr, Dept Pediat, Div Neurodevel & Behav Pediat,Pediat, Rochester, NY 14642 USA. [Schmidt, Brianne L.] Univ Rochester, Med Ctr, Dept Pediat, Div Neurodevel & Behav Pediat, Rochester, NY 14642 USA. [Macklin, Eric A.] Massachusetts Gen Hosp, Ctr Biostat, Med, Boston, MA 02114 USA. [Reynolds, Ann] Univ Colorado Denver, Child Dev Unit, Pediat, Aurora, CO USA. [Reynolds, Ann] Childrens Hosp Colorado, Aurora, CO USA. [Johnson, Cynthia R.] Univ Florida, Coll Publ Hlth & Hlth Profess, Dept Clin & Hlth Psychol, Gainesville, FL USA. [James, S. Jill] Univ Arkansas Med Sci, Childrens Hosp, Res Inst, Pediat, Little Rock, AR USA. [Manning-Courtney, Patricia] Cincinnati Childrens Hosp Med Ctr, Pediat, Cincinnati, OH 45229 USA. RP Stewart, PA (reprint author), Univ Rochester, Med Ctr, 265 Crittenden Blvd,CU420708, Rochester, NY 14642 USA. EM patricia_stewart@urmc.rochester.edu OI Reynolds, Ann/0000-0002-0836-746X; Macklin, Eric/0000-0003-1618-3502 FU Autism Speaks; Health Resources and Services Administration; National Institutes of Health; US Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program [UA3 MC 11054]; University of Rochester Clinical Translational Science Award from the National Center for Advancing Translational Sciences of the National Institutes of Health [UL1 TR000042]; Harvard NeuroDiscovery Center FX This study was funded by Autism Speaks, the Health Resources and Services Administration, and the National Institutes of Health. Additional support came from a cooperative agreement (no. UA3 MC 11054) from the US Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program, to the Massachusetts General Hospital. The project was also supported by the University of Rochester Clinical Translational Science Award (no. UL1 TR000042) from the National Center for Advancing Translational Sciences of the National Institutes of Health, and from the Harvard NeuroDiscovery Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Autism Speaks Autism Treatment Network or the National Institutes of Health. NR 28 TC 7 Z9 7 U1 10 U2 44 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2212-2672 EI 2212-2680 J9 J ACAD NUTR DIET JI J. Acad. Nutr. Diet. PD AUG PY 2015 VL 115 IS 8 BP 1237 EP 1248 DI 10.1016/j.jand.2015.03.026 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CN6IQ UT WOS:000358538700007 PM 26052041 ER PT J AU Powers, MA Bardsley, J Cypress, M Duker, P Funnell, MM Fischl, AH Maryniuk, MD Siminerio, L Vivian, E AF Powers, Margaret A. Bardsley, Joan Cypress, Marjorie Duker, Paulina Funnell, Martha M. Fischl, Amy Hess Maryniuk, Melinda D. Siminerio, Linda Vivian, Eva TI Diabetes Self-Management Education and Support in Type 2 Diabetes: A Joint Position Statement of the American Diabetes Association, the American Association of Diabetes Educators, and the Academy of Nutrition and Dietetics SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; GLYCEMIC CONTROL; CLINICAL-OUTCOMES; DECISION-MAKING; METAANALYSIS; CARE; ADULTS; PEOPLE; NEEDS C1 [Powers, Margaret A.] Int Diabet Ctr Pk Nicollet, Minneapolis, MN 55416 USA. [Bardsley, Joan] MedStar Hlth Res Inst & MedStar Nursing, Special Projects, Hyattsville, MD USA. [Cypress, Marjorie] ABQ Hlth Partners, Endocrinol, Albuquerque, NM USA. [Duker, Paulina] LifeScan, Dubai, U Arab Emirates. [Funnell, Martha M.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Fischl, Amy Hess] Univ Chicago, Chicago, IL 60637 USA. [Maryniuk, Melinda D.] Joslin Diabet Ctr, Joslin Innovat, Care Programs, Boston, MA 02215 USA. [Siminerio, Linda] Univ Pittsburgh, Sch Med, Med, Pittsburgh, PA USA. [Vivian, Eva] Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA. RP Powers, MA (reprint author), Int Diabet Ctr Pk Nicollet, 3800 Pk Nicollet Blvd, Minneapolis, MN 55416 USA. EM margaret.powers@parknicollet.com FU American Diabetes Association; American Association of Diabetes Educators; Academy of Nutrition and Dietetics FX The authors gratefully acknowledge the commitment and support of the collaborating organizations-the American Diabetes Association, the American Association of Diabetes Educators, and the Academy of Nutrition and Dietetics; their colleagues, including members of the Executive Committee of the National Diabetes Education Program, who participated in discussions and reviews about this inaugural position statement; and patients who teach and inspire them. The authors also thank Erika Gebel Berg, PhD (American Diabetes Association) for her invaluable editorial contribution. NR 82 TC 7 Z9 7 U1 6 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2212-2672 EI 2212-2680 J9 J ACAD NUTR DIET JI J. Acad. Nutr. Diet. PD AUG PY 2015 VL 115 IS 8 BP 1323 EP 1334 DI 10.1016/j.jand.2015.05.012 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CN6IQ UT WOS:000358538700017 PM 26054423 ER PT J AU Mavros, MN Bohnen, JD Ramly, EP Velmahos, GC Yeh, DD de Moya, M Fagenholz, P King, DR Lee, J Kaafarani, HMA AF Mavros, Michael N. Bohnen, Jordan D. Ramly, Elie P. Velmahos, George C. Yeh, D. Dante de Moya, Marc Fagenholz, Peter King, David R. Lee, Jarone Kaafarani, Haytham M. A. TI Intraoperative Adverse Events: Risk Adjustment for Procedure Complexity and Presence of Adhesions Is Crucial SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID QUALITY IMPROVEMENT PROGRAM; PATIENT SAFETY INDICATORS; SEVERITY GRADING SYSTEM; SURGICAL CARE; POSTOPERATIVE COMPLICATIONS; AMERICAN-COLLEGE; MULTIVARIABLE PREDICTORS; ABDOMINAL-SURGERY; VASCULAR-SURGERY; LIVER RESECTION AB BACKGROUND: Benchmarking the quality of intraoperative care by comparing the rates of intraoperative adverse events (iAEs) necessitates adequate risk adjustment. We sought to identify the patientand procedure-related risk factors for iAEs. STUDY DESIGN: Our 2007 to 2012 institutional American College of Surgeons NSQIP and administrative databases were linked and then screened for iAEs using the Patient Safety Indicator "Accidental Puncture/Laceration." Intraoperative adverse events were confirmed by systematic review of medical records. Comorbidities were assessed using American College of Surgeons NSQIP variables. Adhesiolysis was determined using CPT codes for lysis of adhesions. Operative complexity was determined using relative value units. Multivariable models were constructed to identify independent predictors of iAEs. Sensitivity analyses were performed in uniform samples of operations. RESULTS: Of 9,292 patients, 218 iAEs were confirmed in 183 patients. Median patient age was 56 years old and 54% were female. Compared with patients without iAEs, iAE patients were older (median 61 vs 56 years; p < 0.001), more functionally dependent (9% vs 5%; p = 0.028), and had higher American Society of Anesthesiologists class (>= 3 in 45% vs 35%; p = 0.004); their procedures were more complex (median relative value units 29 vs 23; p < 0.001), more likely open (48% vs 21%; p < 0.001), and more often required adhesiolysis (44% vs 18%; p < 0.001). In multivariable analyses, adhesiolysis (odds ratio = 2.34; 95% CI, 1.71-3.21; p < 0.001), higher operative complexity (third vs first relative value units quartile: odds ratio = 3.36; 95% CI, 1.66-6.78; p < 0.001; fourth vs first quartile: odds ratio = 5.97; 95% CI, 3.01-11.86; p < 0.001), and open surgical approach (odds ratio = 2.04; 95% CI, 1.39-3.01; p < 0.001) independently predicted iAEs. Sensitivity analyses confirmed adhesiolysis and higher operative complexity as independent iAE predictors. CONCLUSIONS: Adhesiolysis and higher operative complexity predict an increased risk for iAE. Attempts to benchmark the quality of intraoperative care need to adequately risk adjust for these factors. (C) 2015 by the American College of Surgeons C1 [Mavros, Michael N.; Bohnen, Jordan D.; Ramly, Elie P.; Velmahos, George C.; Yeh, D. Dante; de Moya, Marc; Fagenholz, Peter; King, David R.; Lee, Jarone; Kaafarani, Haytham M. A.] Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Mavros, Michael N.; Bohnen, Jordan D.; Ramly, Elie P.; Velmahos, George C.; Yeh, D. Dante; de Moya, Marc; Fagenholz, Peter; King, David R.; Lee, Jarone; Kaafarani, Haytham M. A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Mavros, Michael N.] Med Star Washington Hosp Ctr, Dept Surg, Washington, DC USA. RP Kaafarani, HMA (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. EM hkaafarani@mgh.harvard.edu OI King, David/0000-0003-1028-1478 NR 53 TC 4 Z9 4 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD AUG PY 2015 VL 221 IS 2 BP 345 EP 353 DI 10.1016/j.jamcollsurg.2015.03.045 PG 9 WC Surgery SC Surgery GA CN4EZ UT WOS:000358384400019 PM 26141463 ER PT J AU Stey, AM Russell, MM Zingmond, DS Gibbons, MM Hall, BL Needleman, J Lawson, EH Liu, N Ko, CY AF Stey, Anne M. Russell, Marcia M. Zingmond, David S. Gibbons, Melinda M. Hall, Bruce L. Needleman, Jack Lawson, Elise H. Liu, Nancy Ko, Clifford Y. TI Using Merged Clinical and Claims Registry Data to Identify High Utilizers of Surgical Inpatient Care 1 Year after Colectomy SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID OUTPATIENT PREOPERATIVE EVALUATION; 30-DAY POSTOPERATIVE READMISSIONS; MAJOR GASTROINTESTINAL RESECTIONS; COLORECTAL SURGERY; RISK-FACTORS; LIVER-TRANSPLANTATION; EARLY REHABILITATION; QUALITY IMPROVEMENT; GENERAL-SURGERY; OPERATING-ROOM AB BACKGROUND: Under bundled payment initiatives, providers will be held financially responsible for patients' acute and post-acute care costs. Certain patients, termed high utilizers, use disproportionate shares of resources during 1 year. The aim of this study was to identify high utilizers, describe their costs, and determine whether preoperative characteristics predict high utilizer status. STUDY DESIGN: Colectomy patients with 1-year follow-up were identified in a linked clinical (American College of Surgeons NSQIP) and administrative (Medicare inpatient claims) dataset (2005 to 2008). Cost of inpatient care was calculated by multiplying patient Medicare charges in each cost center by cost-to-charge ratios from the Medicare cost reports. A mixed-effects logistic model quantified the association between preoperative characteristics and being a high utilizer after elective and emergent colectomies. RESULTS: One thousand and fifty-five of 10,561 colectomy patients accounted for >50% of the inpatient care cost of the entire cohort during 1 year postoperatively. This top decile of patients were labeled high utilizers and had substantially greater costs in the following cost centers: intensive care ($36,322 vs $0), respiratory ($2,875 vs $22), radiology ($649 vs $29), and cardiology ($5,057 vs $166) (all p < 0.001). High utilizers more frequently had emergent index colectomies (43% vs 17%; p < 0.001). Patients with American Society of Anesthesiologists class IV and V had 2-fold increased odds of being high utilizers after both elective (odds ratio = 2.72; 95% CI, 1.89-3.90) and emergent colectomies (odds ratio = 2.09; 95% CI, 1.23-3.55). CONCLUSIONS: Patients in the top cost decile account for the majority of costs in the year after colectomy, disproportionately accumulate those costs in particular cost centers, and can be identified preoperatively. (C) 2015 by the American College of Surgeons C1 [Stey, Anne M.] Mt Sinai Med Ctr, Icahn Sch Med, New York, NY 10029 USA. [Stey, Anne M.; Russell, Marcia M.; Zingmond, David S.; Gibbons, Melinda M.; Lawson, Elise H.; Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Needleman, Jack] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Los Angeles, CA 90024 USA. [Russell, Marcia M.; Liu, Nancy] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Hall, Bruce L.; Ko, Clifford Y.] Amer Coll Surg, Chicago, IL USA. [Hall, Bruce L.] Washington Univ, Dept Surg, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Olin Business Sch, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Ctr Hlth Policy, St Louis, MO USA. [Hall, Bruce L.] St Louis VA Med Ctr, St Louis, MO USA. [Hall, Bruce L.] BJC Healthcare St Louis, St Louis, MO USA. RP Stey, AM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, 10940 Wilshire Blvd,Suite 710, Los Angeles, CA 90024 USA. EM as013j@gmail.com FU Robert Wood Johnson Foundation Clinical Scholars(R) program; US Department of Veterans Affairs FX Dr Stey was supported by The Robert Wood Johnson Foundation Clinical Scholars (R) program and the US Department of Veterans Affairs. NR 41 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD AUG PY 2015 VL 221 IS 2 BP 441 EP U706 DI 10.1016/j.jamcollsurg.2015.03.024 PG 12 WC Surgery SC Surgery GA CN4EZ UT WOS:000358384400029 PM 26141469 ER PT J AU Scott, JW Salim, A Sommers, BD Tsai, TC Scott, KW Song, ZR AF Scott, John W. Salim, Ali Sommers, Benjamin D. Tsai, Thomas C. Scott, Kirstin W. Song, Zirui TI Racial and Regional Disparities in the Effect of the Affordable Care Act's Dependent Coverage Provision on Young Adult Trauma Patients SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID SAFETY-NET HOSPITALS; INSURANCE STATUS; HEALTH-INSURANCE; MORTALITY; IMPACT; OUTCOMES; MANDATE; REFORM; POLICY; STATES AB BACKGROUND: Disparities in trauma outcomes based on insurance and race are especially pronounced among young adults who have relatively high uninsured rates and incur a disproportionate share of trauma in the population. The 2010 Dependent Coverage Provision (DCP) of the Affordable Care Act (ACA) allowed young adults to remain on their parent's health insurance plans until age 26 years, leading to >3 million young adults gaining insurance. We investigated the impact of the DCP on racial disparities in coverage expansion among trauma patients. STUDY DESIGN: Using the 2007-2012 National Trauma Data Bank, we compared changes in coverage among 529,844 19- to 25-year-olds with 484,974 controls aged 27 to 34 years not affected by the DCP. Subgroup analyses were conducted by race and ethnicity and by census region. RESULTS: The pre-DCP uninsured rates among young adults were highest among black patients (48.1%) and Hispanic patients (44.3%), and significantly lower among non-Hispanic white patients (28.9%). However, non-Hispanic white young adults experienced a significantly greater absolute reduction in the uninsured rate (-4.9 percentage points) than black (-2.9; p = 0.01) and Hispanic (-1.7; p < 0.001) young adults. These absolute reductions correspond to a 17.0% relative reduction in the uninsured rate for white patients, 6.1% for black patients, and 3.7% for Hispanic patients. Racial disparities in the provision's impact on coverage among trauma patients were largest in the South and West census regions (p < 0.01). CONCLUSIONS: Although the DCP increased insurance coverage for young adult trauma patients of all races, both absolute and relative racial disparities in insurance coverage widened. The extent of these racial disparities also differed by geographic region. Although this policy produced overall progress toward greater coverage among young adults, its heterogeneous impact by race has important implications for future disparities research in trauma. (C) 2015 by the American College of Surgeons C1 [Scott, John W.; Salim, Ali; Tsai, Thomas C.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02120 USA. [Salim, Ali] Brigham & Womens Hosp, Div Trauma Burns & Surg Crit Care, Boston, MA 02120 USA. [Sommers, Benjamin D.] Brigham & Womens Hosp, Dept Med, Dept Surg, Boston, MA 02120 USA. [Sommers, Benjamin D.; Tsai, Thomas C.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Song, Zirui] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Scott, Kirstin W.] Harvard Univ, Fac Arts & Sci, Cambridge, MA 02138 USA. RP Scott, JW (reprint author), Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Dept Surg, One Brigham Circle,1620 Tremont St,4-020, Boston, MA 02120 USA. EM jwscott@partners.org OI Scott, John/0000-0002-9916-6523 FU AHRQ; National Institute for Healthcare Management; Commonwealth Fund; National Institute on Aging [F30-AG039175] FX Drs Sommers serves part-time and Tsai currently serves full-time as advisors in the Office of the Assistant Secretary for Planning and Evaluation, at the US Department of Health and Human Services (HHS). This paper does not represent the views of HHS. Dr Sommers also receives grants from AHRQ, the National Institute for Healthcare Management, and the Commonwealth Fund. Dr Song was supported by a National Research Service Award from the National Institute on Aging (F30-AG039175). NR 33 TC 7 Z9 7 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD AUG PY 2015 VL 221 IS 2 BP 495 EP U761 DI 10.1016/j.jamcollsurg.2015.03.032 PG 8 WC Surgery SC Surgery GA CN4EZ UT WOS:000358384400035 PM 26141468 ER PT J AU Adler, JT Yeh, H Markmann, JF Nguyen, LL AF Adler, Joel T. Yeh, Heidi Markmann, James F. Nguyen, Louis L. TI Market Competition and Density in Liver Transplantation: Relationship to Volume and Outcomes SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID KIDNEY-TRANSPLANTATION; UNITED-STATES; ACCESS; RISK AB BACKGROUND: Liver transplantation centers are unevenly distributed within the Donor Service Areas (DSAs) of the United States. This study assessed how market competition and liver transplantation center density are associated with liver transplantation volume within individual DSAs. STUDY DESIGN: We conducted a retrospective cohort study of 53,156 adult liver transplants in 45 DSAs with 110 transplantation centers identified from the Scientific Registry of Transplant Recipients between 2003 and 2012. The following measures were derived annually for each DSA: market competition using the Herfindahl Hirschman Index, transplantation center density by the Average Nearest Neighbor method, liver quality by the Liver Donor Risk Index, and patient risk by the Model for End-Stage Liver Disease. A hierarchical mixed effects negative binomial regression model of the relationship between liver transplants and market factors was created annually. Patient and graft survival were investigated with a Cox proportional hazards model. RESULTS: Transplantation center density was associated with market competition (p < 0.0001), listings for organ transplantation (p < 0.0001), and Model for End-Stage Liver Disease at transplantation (p = 0.0005). More liver transplantation centers (incidence rate ratio [IRR] = 1.03; p = 0.04), greater market competition (IRR = 1.36; p = 0.02), increased listings (IRR = 1.14; p < 0.0001), more donors (IRR = 1.24; p < 0.0001), and higher Liver Donor Risk Index (IRR = 3.35; p < 0.0001) were associated with more transplants. No market variables were associated with increased mortality after transplantation. CONCLUSIONS: After controlling for demographic and market factors, a greater concentration of centers was associated with more liver transplants without impacting overall survival. These results warrant additional investigation into the relationship between geospatial factors and liver transplantation volume with consideration for the optimization of scarce resources. (C) 2015 by the American College of Surgeons C1 [Adler, Joel T.; Nguyen, Louis L.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Nguyen, Louis L.] Brigham & Womens Hosp, Dept Surg, Div Vasc & Endovasc Surg, Boston, MA 02115 USA. [Adler, Joel T.; Yeh, Heidi; Markmann, James F.] Massachusetts Gen Hosp, Dept Surg, Div Transplant Surg, Boston, MA 02114 USA. RP Nguyen, LL (reprint author), Brigham & Womens Hosp, Div Vasc & Endovasc Surg, 75 Francis St, Boston, MA 02115 USA. EM llnguyen@partners.org OI Adler, Joel/0000-0001-8190-3444 NR 14 TC 4 Z9 4 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD AUG PY 2015 VL 221 IS 2 BP 524 EP 531 DI 10.1016/j.jamcollsurg.2015.04.018 PG 8 WC Surgery SC Surgery GA CN4EZ UT WOS:000358384400039 PM 26206649 ER PT J AU Long, GV Stroyakovskiy, D Gogas, H Levchenko, E de Braud, F Larkin, J Garbe, C Jouary, T Hauschild, A Grob, JJ Chiarion-Sileni, V Lebbe, C Mandala, M Millward, M Arance, A Bondarenko, I Haanen, JBAG Hansson, J Utikal, J Ferraresi, V Kovalenko, N Mohr, P Probachai, V Schadendorf, D Nathan, P Robert, C Ribas, A DeMarini, DJ Irani, JG Swann, S Legos, JJ Jin, F Mookerjee, B Flaherty, K AF Long, Georgina V. Stroyakovskiy, Daniil Gogas, Helen Levchenko, Evgeny de Braud, Filippo Larkin, James Garbe, Claus Jouary, Thomas Hauschild, Axel Grob, Jean-Jacques Chiarion-Sileni, Vanna Lebbe, Celeste Mandala, Mario Millward, Michael Arance, Ana Bondarenko, Igor Haanen, John B. A. G. Hansson, Johan Utikal, Jochen Ferraresi, Virginia Kovalenko, Nadezhda Mohr, Peter Probachai, Volodymr Schadendorf, Dirk Nathan, Paul Robert, Caroline Ribas, Antoni DeMarini, Douglas J. Irani, Jhangir G. Swann, Suzanne Legos, Jeffrey J. Jin, Fan Mookerjee, Bijoyesh Flaherty, Keith TI Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial SO LANCET LA English DT Article ID CLINICAL-TRIALS; MEK INHIBITION; VEMURAFENIB; COBIMETINIB; MUTATIONS AB Background Previously, a study of ours showed that the combination of dabrafenib and trametinib improves progression-free survival compared with dabrafenib and placebo in patients with BRAF Val600Lys/Glu mutation-positive metastatic melanoma. The study was continued to assess the secondary endpoint of overall survival, which we report in this Article. Methods We did this double-blind phase 3 study at 113 sites in 14 countries. We enrolled previously untreated patients with BRAF Val600Glu or Val600Lys mutation-positive unresectable stage IIIC or stage IV melanoma. Participants were computer-randomised (1:1) to receive a combination of dabrafenib (150 mg orally twice daily) and trametinib (2 mg orally once daily), or dabrafenib and placebo. The primary endpoint was progression-free survival and overall survival was a secondary endpoint. This study is registered with ClinicalTrials.gov, number NCT01584648. Findings Between May 4, 2012, and Nov 30, 2012, we screened 947 patients for eligibility, of whom 423 were randomly assigned to receive dabrafenib and trametinib (n=211) or dabrafenib only (n=212). The final data cutoff was Jan 12, 2015, at which time 222 patients had died. Median overall survival was 25.1 months (95% CI 19.2-not reached) in the dabrafenib and trametinib group versus 18.7 months (15.2-23.7) in the dabrafenib only group (hazard ratio [HR] 0.71, 95% CI 0.55-0.92; p=0.0107). Overall survival was 74% at 1 year and 51% at 2 years in the dabrafenib and trametinib group versus 68% and 42%, respectively, in the dabrafenib only group. Based on 301 events, median progression-free survival was 11.0 months (95% CI 8.0-13.9) in the dabrafenib and trametinib group and 8.8 months (5.9-9.3) in the dabrafenib only group (HR 0.67, 95% CI 0.53-0.84; p=0.0004; unadjusted for multiple testing). Treatment-related adverse events occurred in 181 (87%) of 209 patients in the dabrafenib and trametinib group and 189 (90%) of 211 patients in the dabrafenib only group; the most common was pyrexia (108 patients, 52%) in the dabrafenib and trametinib group, and hyperkeratosis (70 patients, 33%) in the dabrafenib only group. Grade 3 or 4 adverse events occurred in 67 (32%) patients in the dabrafenib and trametinib group and 66 (31%) patients in the dabrafenib only group. Interpretation The improvement in overall survival establishes the combination of dabrafenib and trametinib as the standard targeted treatment for BRAF Val600 mutation-positive melanoma. Studies assessing dabrafenib and trametinib in combination with immunotherapies are ongoing. C1 [Long, Georgina V.] Univ Sydney, Melanoma Inst Australia, Sydney, NSW 2006, Australia. [Long, Georgina V.] Mater Hosp, Sydney, NSW, Australia. [Stroyakovskiy, Daniil] Moscow City Oncol Hosp, Moscow, Russia. [Gogas, Helen] Univ Athens, Sch Med, Dept Med, GR-11527 Athens, Greece. [Levchenko, Evgeny] Petrov Res Inst Oncol, St Petersburg, Russia. [de Braud, Filippo] Fdn IRCCS Ist Nazl Tumori, Milan, Italy. [Larkin, James] Royal Marsden Hosp, London SW3 6JJ, England. [Garbe, Claus] Univ Hosp Tuebingen, Dept Dermatol, Tubingen, Germany. [Jouary, Thomas] CHU Bordeaux, Hop St Andre, Dept Dermatol, Bordeaux, France. [Hauschild, Axel] Univ Hosp Schleswig Holstein, Kiel, Germany. [Grob, Jean-Jacques] Aix Marseille Univ, Marseille, France. [Grob, Jean-Jacques] APHM Hosp CHU Timone, Marseille, France. [Chiarion-Sileni, Vanna] Veneto Oncol Inst IRCCS, Melanoma & Oesophageal Oncol Unit, Padua, Italy. [Lebbe, Celeste] Univ Paris Diderot, INSERM U976, APHP Dermatol CIC Hop St Louis, Paris, France. [Mandala, Mario] Papa Giovanni XXIII Canc Ctr Hosp, Bergamo, Italy. [Millward, Michael] Sir Charles Gairdner Hosp, Perth, WA, Australia. [Arance, Ana] Hosp Clin Barcelona, Dept Med Oncol, Barcelona, Spain. [Arance, Ana] Translat Genom & Targeted Therapeut Solid Tumors, Barcelona, Spain. [Bondarenko, Igor] Dnepropetrovsk State Med Acad, Dnepropetrovsk, Ukraine. [Haanen, John B. A. G.] Netherlands Canc Inst, Amsterdam, Netherlands. [Hansson, Johan] Karolinska Inst, Karolinska Univ Hosp Solna, Stockholm, Sweden. [Utikal, Jochen] Heidelberg Univ, Univ Med Ctr Mannheim, Mannheim, Germany. [Utikal, Jochen] German Canc Res Ctr, Heidelberg, Germany. [Ferraresi, Virginia] Ist Nazl Tumori Regina Elena, Rome, Italy. [Kovalenko, Nadezhda] Volograd Reg Oncol Dispensary 3, Volzhsky, Russia. [Mohr, Peter] Elbe Klinikum Stade, Stade, Germany. [Probachai, Volodymr] Dnipropetrovsk State Council, Dnipropetrovsk Clin Oncol Ctr, Dnepropetrovsk, Ukraine. [Schadendorf, Dirk] Univ Hosp Essen, Essen, Germany. [Nathan, Paul] Mt Vernon Canc Ctr, Northwood, Middx, England. [Robert, Caroline] Gustave Roussy, Villejuif Paris Sud, France. [Robert, Caroline] Univ Paris Sud, F-94275 Le Kremlin Bicetre, France. [Ribas, Antoni] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [DeMarini, Douglas J.; Irani, Jhangir G.; Swann, Suzanne; Legos, Jeffrey J.; Mookerjee, Bijoyesh] Novartis Pharmaceut, E Hanover, NJ USA. [Jin, Fan] Merck & Co Inc, Kenilworth, NJ USA. [Flaherty, Keith] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Long, GV (reprint author), Melanoma Inst Australia, 40 Rocklands Rd, Sydney, NSW 2060, Australia. EM georgina.long@sydney.edu.au RI de Braud, Filippo/B-9997-2017; OI de Braud, Filippo/0000-0003-0103-730X; Utikal, Jochen/0000-0001-5316-0241; Bondarenko, Igor/0000-0002-7071-2471 FU GlaxoSmithKline FX This study was funded by GlaxoSmithKline. Most importantly we thank the patients who participated in this study and their families. We also thank the investigators and study staff who contributed to the study, and members of the steering committee and independent data monitoring committee. SciMentum provided editorial support in the form of graphic services. NR 16 TC 157 Z9 158 U1 2 U2 9 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 1 PY 2015 VL 386 IS 9992 BP 444 EP 451 DI 10.1016/S0140-6736(15)60898-4 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA CN9IY UT WOS:000358761700024 PM 26037941 ER PT J AU Liu, JF Matulonis, UA AF Liu, Joyce F. Matulonis, Ursula A. TI Bevacizumab in newly diagnosed ovarian cancer SO LANCET ONCOLOGY LA English DT Editorial Material ID PHASE-III TRIAL; EPITHELIAL OVARIAN; PRIMARY PERITONEAL; FALLOPIAN-TUBE; CHEMOTHERAPY C1 [Liu, Joyce F.; Matulonis, Ursula A.] Dana Farber Canc Inst, Gynecol Oncol Program, Boston, MA 02215 USA. RP Liu, JF (reprint author), Dana Farber Canc Inst, Gynecol Oncol Program, 450 Brookline Ave, Boston, MA 02215 USA. EM joyce_liu@dfci.harvard.edu NR 10 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD AUG PY 2015 VL 16 IS 8 BP 876 EP 878 DI 10.1016/S1470-2045(15)00064-9 PG 4 WC Oncology SC Oncology GA CN6OS UT WOS:000358554700029 PM 26115795 ER PT J AU Goyal, L Chong, DQ Duda, DG Zhu, AX AF Goyal, Lipika Chong, Dawn Q. Duda, Dan G. Zhu, Andrew X. TI Chemotherapy and antiangiogenics in biliary tract cancer SO LANCET ONCOLOGY LA English DT Editorial Material ID PHASE-II; PLUS SORAFENIB; OPEN-LABEL; GEMCITABINE; OXALIPLATIN; MULTICENTER; COMBINATION C1 [Goyal, Lipika; Chong, Dawn Q.; Duda, Dan G.; Zhu, Andrew X.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Chong, Dawn Q.] Natl Canc Ctr, Singapore, Singapore. RP Goyal, L (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM azhu@mgh.harvard.edu NR 10 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 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD AUG PY 2015 VL 16 IS 8 BP 882 EP 883 DI 10.1016/S1470-2045(15)00093-5 PG 2 WC Oncology SC Oncology GA CN6OS UT WOS:000358554700033 PM 26179202 ER PT J AU Ribas, A Puzanov, I Dummer, R Schadendorf, D Hamid, O Robert, C Hodi, FS Schachter, J Pavlick, AC Lewis, KD Cranmer, LD Blank, CU O'Day, SJ Ascierto, PA Salama, AKS Margolin, KA Loquai, C Eigentler, TK Gangadhar, TC Carlino, MS Agarwala, SS Moschos, SJ Sosman, JA Goldinger, SM Shapira-Frommer, R Gonzalez, R Kirkwood, JM Wolchok, JD Eggermont, A Li, XN Zhou, W Zernhelt, AM Lis, J Ebbinghaus, S Kang, SP Daud, A AF Ribas, Antoni Puzanov, Igor Dummer, Reinhard Schadendorf, Dirk Hamid, Omid Robert, Caroline Hodi, F. Stephen Schachter, Jacob Pavlick, Anna C. Lewis, Karl D. Cranmer, Lee D. Blank, Christian U. O'Day, Steven J. Ascierto, Paolo A. Salama, April K. S. Margolin, Kim A. Loquai, Carmen Eigentler, Thomas K. Gangadhar, Tara C. Carlino, Matteo S. Agarwala, Sanjiv S. Moschos, Stergios J. Sosman, Jeffrey A. Goldinger, Simone M. Shapira-Frommer, Ronnie Gonzalez, Rene Kirkwood, John M. Wolchok, Jedd D. Eggermont, Alexander Li, Xiaoyun Nicole Zhou, Wei Zernhelt, Adriane M. Lis, Joy Ebbinghaus, Scot Kang, S. Peter Daud, Adil TI Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial SO LANCET ONCOLOGY LA English DT Article ID ANTI-PD-L1 ANTIBODY; PD-1 BLOCKADE; CANCER; RESPONSES; SAFETY; NIVOLUMAB; MPDL3280A; MUTATION AB Background Patients with melanoma that progresses on ipilimumab and, if BRAF(V600) mutant-positive, a BRAF or MEK inhibitor or both, have few treatment options. We assessed the efficacy and safety of two pembrolizumab doses versus investigator-choice chemotherapy in patients with ipilimumab-refractory melanoma. Methods We carried out a randomised phase 2 trial of patients aged 18 years or older from 73 hospitals, clinics, and academic medical centres in 12 countries who had confirmed progressive disease within 24 weeks after two or more ipilimumab doses and, if BRAF(V600) mutant-positive, previous treatment with a BRAF or MEK inhibitor or both. Patients had to have resolution of all ipilimumab-related adverse events to grade 0-1 and prednisone 10 mg/day or less for at least 2 weeks, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and at least one measurable lesion to be eligible. Using a centralised interactive voice response system, we randomly assigned (1:1:1) patients in a block size of six to receive intravenous pembrolizumab 2 mg/kg or 10 mg/kg every 3 weeks or investigator-choice chemotherapy (paclitaxel plus carboplatin, paclitaxel, carboplatin, dacarbazine, or oral temozolomide). Randomisation was stratified by ECOG performance status, lactate dehydrogenase concentration, and BRAFV600 mutation status. Individual treatment assignment between pembrolizumab and chemotherapy was open label, but investigators and patients were masked to assignment of the dose of pembrolizumab. We present the primary endpoint at the prespecified second interim analysis of progression-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01704287. The study is closed to enrolment but continues to follow up and treat patients. Findings Between Nov 30, 2012, and Nov 13, 2013, we enrolled 540 patients:180 patients were randomly assigned to receive pembrolizumab 2 mg/kg, 181 to receive pembrolizumab 10 mg/kg, and 179 to receive chemotherapy. Based on 410 progression-free survival events, progression-free survival was improved in patients assigned to pembrolizumab 2 mg/kg (HR 0.57, 95% CI 0.45-0.73; p<0.0001) and those assigned to pembrolizumab 10 mg/kg (0.50, 0.39-0.64; p<0.0001) compared with those assigned to chemotherapy. 6-month progression-free survival was 34% (95% CI 27-41) in the pembrolizumab 2 mg/kg group, 38% (31-45) in the 10 mg/kg group, and 16% (10-22) in the chemotherapy group. Treatment-related grade 3-4 adverse events occurred in 20 (11%) patients in the pembrolizumab 2 mg/kg group, 25 (14%) in the pembrolizumab 10 mg/kg group, and 45 (26%) in the chemotherapy group. The most common treatment-related grade 3-4 adverse event in the pembrolizumab groups was fatigue (two [1%] of 178 patients in the 2 mg/kg group and one [< 1%] of 179 patients in the 10 mg/kg group, compared with eight [5%] of 171 in the chemotherapy group). Other treatment-related grade 3-4 adverse events include generalised oedema and myalgia (each in two [1%] patients) in those given pembrolizumab 2 mg/kg; hypopituitarism, colitis, diarrhoea, decreased appetite, hyponatremia, and pneumonitis (each in two [1%]) in those given pembrolizumab 10 mg/kg; and anaemia (nine [5%]), fatigue (eight [5%]), neutropenia (six [4%]), and leucopenia (six [4%]) in those assigned to chemotherapy. Interpretation These findings establish pembrolizumab as a new standard of care for the treatment of ipilimumab-refractory melanoma. C1 [Ribas, Antoni] Univ Calif Los Angeles, Los Angeles, CA 90095 USA. [Puzanov, Igor] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Dummer, Reinhard; Goldinger, Simone M.] Univ Zurich, Zurich, Switzerland. [Schadendorf, Dirk] Univ Hosp Essen, Essen, Germany. [Hamid, Omid] Angeles Clin & Res Inst, Los Angeles, CA USA. [Robert, Caroline; Eggermont, Alexander] Gustave Roussy & Paris Sud Univ, Villejuif, France. [Hodi, F. Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Schachter, Jacob; Shapira-Frommer, Ronnie] Sheba Med Ctr, Tel Hashomer, Israel. [Pavlick, Anna C.] NYU, Inst Canc, New York, NY USA. [Lewis, Karl D.; Gonzalez, Rene] Univ Colorado Denver, Aurora, CO USA. [Cranmer, Lee D.] Univ Arizona, Ctr Canc, Tucson, AZ USA. [Blank, Christian U.] Netherlands Canc Inst, Amsterdam, Netherlands. [O'Day, Steven J.] Beverly Hills Canc Ctr, Beverly Hills, CA USA. [Ascierto, Paolo A.] Ist Nazl Tumori Fdn G Pascale, Naples, Italy. [Salama, April K. S.] Duke Canc Inst, Durham, NC USA. [Margolin, Kim A.] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Loquai, Carmen] Univ Med Ctr, Mainz, Germany. [Eigentler, Thomas K.] Univ Klinikum Tubingen, Tubingen, Germany. [Gangadhar, Tara C.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Carlino, Matteo S.] Westmead Hosp, Crown Princess Mary Canc Ctr, Westmead, NSW 2145, Australia. [Carlino, Matteo S.] Blacktown Hosp, Westmead, NSW, Australia. [Carlino, Matteo S.] Melanoma Inst Australia, Westmead, NSW, Australia. [Agarwala, Sanjiv S.] St Lukes Canc Ctr, Bethlehem, PA USA. [Agarwala, Sanjiv S.] Temple Univ, Philadelphia, PA 19122 USA. [Moschos, Stergios J.] Univ N Carolina, Chapel Hill, NC USA. [Kirkwood, John M.] Univ Pittsburgh, Pittsburgh, PA USA. [Wolchok, Jedd D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Li, Xiaoyun Nicole; Zhou, Wei; Zernhelt, Adriane M.; Lis, Joy; Ebbinghaus, Scot; Kang, S. Peter] Merck & Co Inc, Kenilworth, NJ USA. [Daud, Adil] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Ribas, A (reprint author), Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Hematol Oncol, Dept Med, Los Angeles, CA 90095 USA. EM aribas@mednet.ucla.edu RI Eigentler, Thomas/K-8570-2015 OI Eigentler, Thomas/0000-0003-0019-2770 FU Merck Sharp Dohme FX This study and assistance with manuscript editing were funded by Merck Sharp & Dohme. We thank the patients and their families and caregivers; all primary investigators and their site personnel (see appendix); Tricia Brown and Melanie Leiby (The APO Group, Yardley, PA, USA), for assistance with manuscript editing; James R Anderson (University of Nebraska Medical Center, Omaha, NE, USA), Ronald Blum (Albert Einstein College of Medicine and Beth Israel Medical Center, New York, NY, USA), Janice Dutcher (Cancer Research Foundation, New York, NY, USA), and Lawrence Flaherty (Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA), for serving on the external data monitoring committee; Jeff Maca (Quintiles, Morrisville, SC, USA), for serving as the unmasked study statistician; Eric Rubin and Alise Reicin (Merck Sharp & Dohme), for critical review of the manuscript and supervision of the study group; Cong Chen (Merck) for critical review of the manuscript and statistical expertise; and Clara Benner, Linda Gammage, Claudia Geis, Klaas Koekenbier, Amanda McDonald, Kathleen Oxberry, Lei Pang, Theodora Paraskevopoulos, Andrea Perrone, Kathryn Schneck, Sigalit Segal, Sophie Vauclair, and Jen Villetard (all of Merck) for critical study support. NR 30 TC 236 Z9 242 U1 13 U2 32 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD AUG PY 2015 VL 16 IS 8 BP 908 EP 918 DI 10.1016/S1470-2045(15)00083-2 PG 11 WC Oncology SC Oncology GA CN6OS UT WOS:000358554700043 PM 26115796 ER PT J AU Cao, C D'Amico, T Demmy, T Dunning, J Gossot, D Hansen, H He, JX Jheon, S Petersen, RH Sihoe, A Swanson, S Walker, W Yan, TD AF Cao, Christopher D'Amico, Thomas Demmy, Todd Dunning, Joel Gossot, Dominique Hansen, Henrik He, Jianxing Jheon, Sanghoon Petersen, Rene H. Sihoe, Alan Swanson, Scott Walker, William Yan, Tristan D. CA Int VATS Interest Grp TI Surgery versus SABR for resectable non-small-cell lung cancer SO LANCET ONCOLOGY LA English DT Letter ID LOBECTOMY; TRIALS C1 [Cao, Christopher; Yan, Tristan D.] Macquarie Univ, Collaborat Res CORE Grp, Sydney, NSW 2109, Australia. [D'Amico, Thomas] Duke Univ, Sch Med, Dept Surg, Durham, NC USA. [Demmy, Todd] Robert Wood Johnson Med Sch, Rutgers Canc Inst New Jersey, Dept Surg, Brunswick, NJ USA. [Dunning, Joel] James Cook Univ Hosp, Dept Cardiothorac Surg, Middlesbrough, England. [Gossot, Dominique] Inst Mutualiste Montsouris, Dept Thorac Surg, Paris, France. [Hansen, Henrik] Univ Copenhagen Hosp, Rigshosp, Dept Cardiothorac Surg, DK-2100 Copenhagen, Denmark. [He, Jianxing] Guangzhou Med Univ, Affiliated Hosp 1, Dept Thorac Surg, Guangzhou, Peoples R China. [Jheon, Sanghoon] Seoul Natl Univ, Bundang Hosp, Coll Med, Dept Thorac & Cardiovasc Surg, Seoul, South Korea. [Petersen, Rene H.] Univ Copenhagen Hosp, Rigshosp, Dept Cardiothorac Surg, DK-2100 Copenhagen, Denmark. [Sihoe, Alan] Univ Hong Kong, Dept Surg, Hong Kong, Hong Kong, Peoples R China. [Swanson, Scott] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Swanson, Scott] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Walker, William] Royal Infirm, Dept Cardiothorac Surg, Edinburgh, Midlothian, Scotland. [Yan, Tristan D.] Royal Prince Alfred Hosp, Dept Cardiothorac Surg, Sydney, NSW, Australia. RP Cao, C (reprint author), Macquarie Univ, Collaborat Res CORE Grp, Sydney, NSW 2109, Australia. EM tristanyan@annalscts.com NR 8 TC 7 Z9 7 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD AUG PY 2015 VL 16 IS 8 BP E370 EP E371 PG 2 WC Oncology SC Oncology GA CN6OS UT WOS:000358554700001 PM 26248836 ER PT J AU Stulac, S Binagwaho, A Tapela, NM Wagner, CM Muhimpundu, MA Ngabo, F Nsanzimana, S Kayonde, L Bigirimana, JB Lessard, AJ Lehmann, L Shulman, LN Nutt, CT Drobac, P Mpunga, T Farmer, PE AF Stulac, Sara Binagwaho, Agnes Tapela, Neo M. Wagner, Claire M. Muhimpundu, Marie Aimee Ngabo, Fidele Nsanzimana, Sabin Kayonde, Leonard Bigirimana, Jean Bosco Lessard, Adam J. Lehmann, Leslie Shulman, Lawrence N. Nutt, Cameron T. Drobac, Peter Mpunga, Tharcisse Farmer, Paul E. TI Capacity building for oncology programmes in sub-Saharan Africa: the Rwanda experience SO LANCET ONCOLOGY LA English DT Article ID RURAL RWANDA; NONCOMMUNICABLE DISEASES; HUMAN-PAPILLOMAVIRUS; PATHOLOGY SERVICES; CERVICAL-CANCER; HUMAN-RESOURCES; HEALTH SYSTEMS; GLOBAL HEALTH; MIDDLE-INCOME; COUNTRIES AB Despite an estimated 456 000 deaths caused by cancer in sub-Saharan Africa in 2012 and a cancer burden that is predicted to double by 2030, the region accounts for only 0.3% of worldwide medical expenditure for cancer. Challenges to cancer care in sub-Saharan Africa include a shortage of clinicians and training programmes, weak healthcare infrastructure, and inadequate supplies. Since 2011, Rwanda has developed a national cancer programme by designing comprehensive, integrated frameworks of care, building local human resource capacity through partnerships, and delivering equitable, rights-based care. In the 2 years since the inauguration of Rwanda's fi rst cancer centre, more than 2500 patients have been enrolled, including patients from every district in Rwanda. Based on Rwanda's national cancer programme development, we suggest principles that could guide other nations in the development of similar cancer programmes. C1 [Stulac, Sara; Tapela, Neo M.; Drobac, Peter] Brigham & Womens Hosp, Boston, MA 02115 USA. [Binagwaho, Agnes; Muhimpundu, Marie Aimee; Ngabo, Fidele; Nsanzimana, Sabin; Kayonde, Leonard] Minist Hlth Rwanda, Kigali, Rwanda. [Wagner, Claire M.] Global Hlth Delivery Partnership, Boston, MA USA. [Bigirimana, Jean Bosco] Inshuti Mu Buzima, Rwinkwavu, Rwanda. [Lessard, Adam J.; Lehmann, Leslie; Shulman, Lawrence N.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nutt, Cameron T.] Partners Hlth, Boston, MA USA. [Mpunga, Tharcisse] Univ Rwanda, Coll Med & Hlth Serv, Kigali, Rwanda. [Farmer, Paul E.] Harvard Univ, Sch Med, Boston, MA USA. RP Stulac, S (reprint author), Brigham & Womens Hosp, Boston, MA 02115 USA. EM sstulac@pih.org NR 64 TC 11 Z9 11 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD AUG PY 2015 VL 16 IS 8 BP E405 EP E413 PG 9 WC Oncology SC Oncology GA CN6OS UT WOS:000358554700023 PM 26248848 ER PT J AU Egede, LE Acierno, R Knapp, RG Lejuez, C Hernandez-Tejada, M Payne, EH Frueh, BC AF Egede, Leonard E. Acierno, Ron Knapp, Rebecca G. Lejuez, Carl Hernandez-Tejada, Melba Payne, Elizabeth H. Frueh, B. Christopher TI Psychotherapy for depression in older veterans via telemedicine: a randomised, open-label, non-inferiority trial SO LANCET PSYCHIATRY LA English DT Article ID BEHAVIORAL ACTIVATION TREATMENT; POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH RESEARCH; MAJOR DEPRESSION; COLLABORATIVE CARE; LATER LIFE; ADULTS; POPULATION; THERAPY; PROGRAM AB Background Many older adults with major depression, particularly veterans, do not have access to evidence-based psychotherapy. Telemedicine could increase access to best-practice care for older adults facing barriers of mobility, stigma, and geographical isolation. We aimed to establish non-inferiority of behavioural activation therapy for major depression delivered via telemedicine to same-room care in largely male, older adult veterans. Methods In this randomised, controlled, open-label, non-inferiority trial, we recruited veterans (aged >= 58 years) meeting DSM-IV criteria for major depressive disorder from the Ralph H Johnson Veterans Affairs Medical Center and four associated community outpatient-based clinics in the USA. We excluded actively psychotic or demented people, those with both suicidal ideation and clear intent, and those with substance dependence. The study coordinator randomly assigned participants (1:1; block size 2-6; stratified by race; computer-generated randomisation sequence by RGK) to eight sessions of behavioural activation for depression either via telemedicine or in the same room. The primary outcome was treatment response according to the Geriatric Depression Scale (GDS) and Beck Depression Inventory (BDI; defined as a 50% reduction in symptoms from baseline at 12 months), and Structured Clinical Interview for DSM-IV, clinician version (defined as no longer being diagnosed with major depressive disorder at 12 months follow-up), in the per-protocol population (those who completed at least four treatment sessions and for whom all outcome measurements were done). Those assessing outcomes were masked. The non-inferiority margin was 15%. This trial is registered with ClinicalTrials.gov, number NCT00324701. Findings Between April 1, 2007, and July 31, 2011, we screened 780 patients, and the study coordinator randomly assigned participants to either telemedicine (120 [50%]) or same-room treatment (121 [50%]). We included 100 (83%) patients in the per-protocol analysis in the telemedicine group and 104 (86%) in the same-room group. Treatment response according to GDS did not differ significantly between the telemedicine (22 [22.45%, 90% CI 15.52-29.38] patients) and same-room (21 [20.39%, 90% CI 13.86-26.92]) groups, with an absolute difference of 2.06% (90% CI -7.46 to 11.58). Response according to BDI also did not differ significantly (telemedicine 19 [24.05%, 90% CI 16.14-31.96] patients; same room 19 [23.17%, 90% CI 15.51-30.83]), with an absolute difference of 0.88% (90% CI -10.13 to 11.89). Response on the Structured Clinical Interview for DSM-IV, clinician version, also did not differ significantly (39 [43.33%, 90% CI 34.74-51.93] patients in the telemedicine group and 46 [48.42%, 90% CI 39.99-56.85] in the same-room group), with a difference of -5.09% (-17.13 to 6.95; p=0.487). Results from the intention-to-treat population were similar. MEM analyses showed that no significant differences existed between treatment trajectories over time for BDI and GDS. The criteria for non-inferiority were met. We did not note any adverse events. Interpretation Telemedicine-delivered psychotherapy for older adults with major depression is not inferior to same-room treatment. This finding shows that evidence-based psychotherapy can be delivered, without modification, via home-based telemedicine, and that this method can be used to overcome barriers to care associated with distance from and difficulty with attendance at in-person sessions in older adults. C1 [Egede, Leonard E.; Acierno, Ron; Knapp, Rebecca G.; Lejuez, Carl; Payne, Elizabeth H.; Frueh, B. Christopher] Ralph H Johnson Vet Affairs Med Ctr, Hlth Equ & Rural Outreach Innovat Ctr, Charleston, SC USA. [Egede, Leonard E.; Hernandez-Tejada, Melba] Med Univ S Carolina, Ctr Hlth Dispar Res, Div Gen Internal Med, Charleston, SC 29425 USA. [Acierno, Ron; Hernandez-Tejada, Melba] Med Univ S Carolina, Coll Nursing, Charleston, SC 29425 USA. [Knapp, Rebecca G.; Payne, Elizabeth H.] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. [Lejuez, Carl] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. [Frueh, B. Christopher] Univ Hawaii, Dept Psychol, Hilo, HI 96720 USA. [Frueh, B. Christopher] Menninger Clin, Houston, TX USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. EM egedel@musc.edu FU Veterans Affairs Health Services Research and Development Program [IIR-04-421-3] FX This work was supported by grants IIR-04-421-3 from the Veterans Affairs Health Services Research and Development Program. We are deeply appreciative of the veterans and Veterans Affairs primary care and mental health providers who contributed to this research effort. All views and opinions expressed herein are those of the authors and do not necessarily reflect those of our respective institutions or the Department of Veterans Affairs. NR 53 TC 14 Z9 14 U1 4 U2 27 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 2015 VL 2 IS 8 BP 693 EP 701 DI 10.1016/S2215-0366(15)00122-4 PG 9 WC Psychiatry SC Psychiatry GA CN9CH UT WOS:000358743200021 PM 26249300 ER PT J AU Pavlova, B Perlis, RH Alda, M Uher, R AF Pavlova, Barbara Perlis, Roy H. Alda, Martin Uher, Rudolf TI Lifetime prevalence of anxiety disorders in people with bipolar disorder: a systematic review and meta-analysis SO LANCET PSYCHIATRY LA English DT Article ID COMORBIDITY SURVEY REPLICATION; TREATMENT ENHANCEMENT PROGRAM; QUALITY-OF-LIFE; I DISORDER; CLINICAL CHARACTERISTICS; MAJOR DEPRESSION; SOCIAL PHOBIA; SELF-ESTEEM; STEP-BD; RISK AB Background Anxiety disorders are increasingly recognised as an important determinant of outcomes in patients with bipolar disorder. However, a reliable estimate of their prevalence is still missing, because the published prevalence of anxiety disorders in individuals with bipolar disorder varies widely. In this study, we aimed to quantify the lifetime prevalence of anxiety disorders in individuals with bipolar disorder and compare it with rates in people without the disorder. Methods We searched the Web of Knowledge and Medline (through the PubMed interface) for articles published in any language from the database inception dates up until June 1, 2014, using a combination of the word "bipolar" and search terms for anxiety disorders. We included studies that reported original data about the lifetime prevalence of DSM-III and DSM-IV anxiety disorders in adults with bipolar disorder that recruited participants irrespective of comorbidities and that used a validated diagnostic interview to establish the diagnoses of bipolar disorder and at least one anxiety disorder. We excluded studies that reported only the current prevalence or if we were unable to establish whether they described current or lifetime prevalence, and those with discrepancies in the data that could not be resolved by contacting the authors. We did a random-effects meta-analysis of lifetime prevalence of DSM-III and DSM-IV anxiety disorders in adults with bipolar disorder, in which we quantified the lifetime prevalence of any anxiety disorder in people with bipolar disorder. We compared this prevalence in people with bipolar I disorder versus those with bipolar II disorder, and in people with bipolar disorder versus population controls. Findings Data from 40 studies, including 14 914 individuals from North America, Europe, Australia, South America, and Asia, indicate that the lifetime prevalence of anxiety disorders in individuals with bipolar disorder is 45% (95% CI 40-51). Direct comparison in five samples with a total of 1378 individuals with bipolar disorder and 56 812 population controls without bipolar disorder indicates a three-fold increase (risk ratio [RR] 3.22 [95% CI 2.41-4.29]; p<0.0001) in the prevalence of anxiety disorders in those with bipolar disorder. 13 studies that included both individuals with bipolar I disorder (n=4270) and those with bipolar II disorder (n=1939) showed no difference in the lifetime prevalence of anxiety disorders between these subtypes (RR 1.07 [95% CI 0.96-1.20]; p=0.223). We noted significant heterogeneity among included studies that was not accounted for by reported differences in study characteristics. Interpretation People with bipolar disorder are at increased risk of anxiety disorders compared with those without bipolar disorder; nearly one in two has an anxiety disorder in their lifetime. Anxiety disorders should therefore be assessed alongside the mood symptoms in patients with bipolar disorder. C1 [Pavlova, Barbara; Alda, Martin; Uher, Rudolf] Nova Scotia Hlth Author, Halifax, NS, Canada. [Perlis, Roy H.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Pavlova, Barbara; Alda, Martin; Uher, Rudolf] Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada. RP Pavlova, B (reprint author), Dalhousie Univ, Dept Psychiat, Mood Disorders Program, 5909 Vet Mem Lane, Halifax, NS B3H 2E2, Canada. EM barbara.pavlova@dal.ca FU Capital Health Research Fund, Capital District Health Authority (Halifax, NS, Canada) FX This work has been generously supported by the Capital Health Research Fund, Capital District Health Authority (Halifax, NS, Canada). We thank the National Institute of Mental Health (for the National Comorbidity Survey Replication), Keming Gao, Nader Perroud, and Philip Mitchell for providing a substantial amount of additional data for this meta-analysis. NR 49 TC 13 Z9 13 U1 0 U2 14 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 2015 VL 2 IS 8 BP 710 EP 717 DI 10.1016/S2215-0366(15)00112-1 PG 8 WC Psychiatry SC Psychiatry GA CN9CH UT WOS:000358743200023 PM 26249302 ER PT J AU Cauley, SF Setsompop, K Ma, D Jiang, Y Ye, HH Adalsteinsson, E Griswold, MA Wald, LL AF Cauley, Stephen F. Setsompop, Kawin Ma, Dan Jiang, Yun Ye, Huihui Adalsteinsson, Elfar Griswold, Mark A. Wald, Lawrence L. TI Fast group matching for MR fingerprinting reconstruction SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MR fingerprinting; clustering; matching; pruning ID PROTON DENSITY; QUANTIFICATION; TRUEFISP; SIGNAL; BRAIN; T-1; TRAJECTORIES; RELAXATION; RECOVERY; DISEASE AB PurposeMR fingerprinting (MRF) is a technique for quantitative tissue mapping using pseudorandom measurements. To estimate tissue properties such as T-1, T-2, proton density, and B-0, the rapidly acquired data are compared against a large dictionary of Bloch simulations. This matching process can be a very computationally demanding portion of MRF reconstruction. Theory and MethodsWe introduce a fast group matching algorithm (GRM) that exploits inherent correlation within MRF dictionaries to create highly clustered groupings of the elements. During matching, a group specific signature is first used to remove poor matching possibilities. Group principal component analysis (PCA) is used to evaluate all remaining tissue types. In vivo 3 Tesla brain data were used to validate the accuracy of our approach. ResultsFor a trueFISP sequence with over 196,000 dictionary elements, 1000 MRF samples, and image matrix of 128 x 128, GRM was able to map MR parameters within 2s using standard vendor computational resources. This is an order of magnitude faster than global PCA and nearly two orders of magnitude faster than direct matching, with comparable accuracy (1-2% relative error). ConclusionThe proposed GRM method is a highly efficient model reduction technique for MRF matching and should enable clinically relevant reconstruction accuracy and time on standard vendor computational resources. Magn Reson Med 74:523-528, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [Cauley, Stephen F.; Setsompop, Kawin; Ye, Huihui; Adalsteinsson, Elfar; Wald, Lawrence L.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Cauley, Stephen F.; Setsompop, Kawin; Wald, Lawrence L.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Ma, Dan; Jiang, Yun; Griswold, Mark A.] Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA. [Ye, Huihui] Zhejiang Univ, Dept Biomed Engn, Hangzhou 310003, Zhejiang, Peoples R China. [Adalsteinsson, Elfar; Wald, Lawrence L.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Adalsteinsson, Elfar; Wald, Lawrence L.] MIT, Harvard Mit Div Hlth Sci & Technol, Inst Med Engn & Sci, Cambridge, MA 02139 USA. [Griswold, Mark A.] Case Western Reserve Univ, Dept Radiol, Cleveland, OH 44106 USA. [Griswold, Mark A.] Univ Hosp Cleveland, Cleveland, OH 44106 USA. RP Cauley, SF (reprint author), 149 13th St,Room 2301, Charlestown, MA 02129 USA. EM stcauley@nmr.mgh.harvard.edu RI Wald, Lawrence/D-4151-2009 FU National Institutes of Health (NIH) [R01EB006847, R00EB012107, R01EB017219, P41RR014075, U01MH093765] FX Grant sponsor: National Institutes of Health (NIH); Grant numbers: R01EB006847, R00EB012107, R01EB017219, P41RR014075, and U01MH093765. NR 26 TC 7 Z9 7 U1 2 U2 13 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 2015 VL 74 IS 2 BP 523 EP 528 DI 10.1002/mrm.25439 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN7IK UT WOS:000358607700028 PM 25168690 ER PT J AU Patsch, C Challet-Meylan, L Thoma, EC Urich, E Heckel, T O'Sullivan, JF Grainger, SJ Kapp, FG Sun, L Christensen, K Xia, YL Florido, MHC He, W Pan, W Prummer, M Warren, CR Jakob-Roetne, R Certa, U Jagasia, R Freskgard, PO Adatto, I Kling, D Huang, P Zon, LI Chaikof, EL Gerszten, RE Graf, M Iacone, R Cowan, CA AF Patsch, Christoph Challet-Meylan, Ludivine Thoma, Eva C. Urich, Eduard Heckel, Tobias O'Sullivan, John F. Grainger, Stephanie J. Kapp, Friedrich G. Sun, Lin Christensen, Klaus Xia, Yulei Florido, Mary H. C. He, Wei Pan, Wei Prummer, Michael Warren, Curtis R. Jakob-Roetne, Roland Certa, Ulrich Jagasia, Ravi Freskgard, Per-Ola Adatto, Isaac Kling, Dorothee Huang, Paul Zon, Leonard I. Chaikof, Elliot L. Gerszten, Robert E. Graf, Martin Iacone, Roberto Cowan, Chad A. TI Generation of vascular endothelial and smooth muscle cells from human pluripotent stem cells SO NATURE CELL BIOLOGY LA English DT Article ID IN-VIVO; DIRECTED DIFFERENTIATION; DEFINITIVE ENDODERM; HUMAN BLASTOCYSTS; STROMAL CELLS; GROWTH-FACTOR; WNT; CULTURE; LINES; MOUSE AB The use of human pluripotent stem cells for in vitro disease modelling and clinical applications requires protocols that convert these cells into relevant adult cell types. Here, we report the rapid and efficient differentiation of human pluripotent stem cells into vascular endothelial and smooth muscle cells. We found that GSK3 inhibition and BMP4 treatment rapidly committed pluripotent cells to a mesodermal fate and subsequent exposure to VEGF-A or PDGF-BB resulted in the differentiation of either endothelial or vascular smooth muscle cells, respectively. Both protocols produced mature cells with efficiencies exceeding 80% within six days. On purification to 99% via surface markers, endothelial cells maintained their identity, as assessed by marker gene expression, and showed relevant in vitro and in vivo functionality. Global transcriptional and metabolomic analyses confirmed that the cells closely resembled their in vivo counterparts. Our results suggest that these cells could be used to faithfully model human disease. C1 [Patsch, Christoph; Thoma, Eva C.; Urich, Eduard; Heckel, Tobias; Christensen, Klaus; He, Wei; Pan, Wei; Prummer, Michael; Jakob-Roetne, Roland; Certa, Ulrich; Jagasia, Ravi; Freskgard, Per-Ola; Kling, Dorothee; Graf, Martin; Iacone, Roberto] Roche Innovat Ctr Basel, Roche Pharmaceut Res & Early Dev, CH-4070 Basel, Switzerland. [Challet-Meylan, Ludivine; Xia, Yulei; Florido, Mary H. C.; Warren, Curtis R.; Zon, Leonard I.; Cowan, Chad A.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Challet-Meylan, Ludivine; Xia, Yulei; Florido, Mary H. C.; Warren, Curtis R.; Zon, Leonard I.; Cowan, Chad A.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [O'Sullivan, John F.; Sun, Lin; Adatto, Isaac; Huang, Paul; Gerszten, Robert E.; Cowan, Chad A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [O'Sullivan, John F.; Sun, Lin; Adatto, Isaac; Huang, Paul; Gerszten, Robert E.; Cowan, Chad A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [O'Sullivan, John F.; Sun, Lin; Adatto, Isaac; Huang, Paul; Gerszten, Robert E.; Cowan, Chad A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Grainger, Stephanie J.; Chaikof, Elliot L.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02115 USA. [Grainger, Stephanie J.; Chaikof, Elliot L.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Kapp, Friedrich G.; Zon, Leonard I.; Cowan, Chad A.] Boston Childrens Hosp, Stem Cell Program, Boston, MA USA. [Kapp, Friedrich G.; Zon, Leonard I.; Cowan, Chad A.] Boston Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA. [Kapp, Friedrich G.; Zon, Leonard I.; Cowan, Chad A.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Patsch, C (reprint author), Roche Innovat Ctr Basel, Roche Pharmaceut Res & Early Dev, CH-4070 Basel, Switzerland. EM christoph.patsch@roche.com; chad_cowan@harvard.edu RI Prummer, Michael/G-6464-2011 OI Prummer, Michael/0000-0001-9896-3929 FU Roche Postdoctoral Fellowships (RPF); Innovative Medicines Initiative Joint Undertaking [115439]; European Union; EFPIA companies; Swiss National Science Foundation; German Cancer Aid; HHMI; NIH [R01 HL04880, 5P30 DK49216, 5R01 DK53298, 5U01 HL10001-05, R24 DK092760, HL106018, HL083867, HL60963, 2R01DK081572, R01DK097768, U01HL100408]; Harvard Stem Cell Institute and Harvard University FX We thank A. Einhaus, S. Zimmermann, C. Stucki and N. Dahm for excellent technical support and all members of the Roche Stem Cell Platform for helpful discussions. We thank C. MacGillivray at the HSCRB Histology Core facility. We also thank S. Aigner and C. Warren for critically reviewing the manuscript and A. Gundner, C. Hudak and K. Song for help with the illustrations. We acknowledge the continued support of H.-L. Roche and thank M. Steger from Roche Pharma Partnering for his input and support of the project. C.P. and E.C.T. were supported by Roche Postdoctoral Fellowships (RPF). A part of the research received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement number 115439, resources of which are composed of financial contribution from the European Union's Seventh Framework Program (FP7/2007-2013) and EFPIA companies' in kind contribution. L.C.-M. was supported by a fellowship from the Swiss National Science Foundation. F.G.K. was supported by a fellowship from the German Cancer Aid. This work was supported by HHMI and NIH grants R01 HL04880, 5P30 DK49216, 5R01 DK53298, 5U01 HL10001-05, and R24 DK092760 (to L.I.Z.); HL106018, HL083867, HL60963 (E.L.C.); 2R01DK081572 and an AHA Established Investigator Award (R.E.G.); R01DK097768, U01HL100408, the Harvard Stem Cell Institute and Harvard University (C.A.C.). NR 55 TC 29 Z9 30 U1 8 U2 28 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 EI 1476-4679 J9 NAT CELL BIOL JI Nat. Cell Biol. PD AUG PY 2015 VL 17 IS 8 BP 994 EP U294 DI 10.1038/ncb3205 PG 19 WC Cell Biology SC Cell Biology GA CO0NE UT WOS:000358847700007 PM 26214132 ER PT J AU Soria-Valles, C Osorio, FG Gutierrez-Fernandez, A De Los Angeles, A Bueno, C Menedez, P Martin-Subero, JI Daley, GQ Freije, JMP Lopez-Otin, C AF Soria-Valles, Clara Osorio, Fernando G. Gutierrez-Fernandez, Ana De Los Angeles, Alejandro Bueno, Clara Menendez, Pablo Martin-Subero, Jose I. Daley, George Q. Freije, Jose M. P. Lopez-Otin, Carlos TI NF-kappa B activation impairs somatic cell reprogramming in ageing SO NATURE CELL BIOLOGY LA English DT Article ID PLURIPOTENT STEM-CELLS; GILFORD PROGERIA SYNDROME; SECRETORY PHENOTYPE; NUCLEAR-ENVELOPE; MICE DEFICIENT; SENESCENCE; METHYLATION; DISEASE; FIBROBLASTS; INHIBITION AB Ageing constitutes a critical impediment to somatic cell reprogramming. We have explored the regulatory mechanisms that constitute age-associated barriers, through derivation of induced pluripotent stem cells (iPSCs) from individuals with premature or physiological ageing. We demonstrate that NF-kappa B activation blocks the generation of iPSCs in ageing. We also show that NF-kappa B repression occurs during cell reprogramming towards a pluripotent state. Conversely, ageing-associated NF-kappa B hyperactivation impairs the generation of iPSCs by eliciting the reprogramming repressor DOT1L, which reinforces senescence signals and downregulates pluripotency genes. Genetic and pharmacological NF-kappa B inhibitory strategies significantly increase the reprogramming efficiency of fibroblasts from Nestor-Guillermo progeria syndrome and Hutchinson-Gilford progeria syndrome patients, as well as from normal aged donors. Finally, we demonstrate that DOT1L inhibition in vivo extends lifespan and ameliorates the accelerated ageing phenotype of progeroid mice, supporting the interest of studying age-associated molecular impairments to identify targets of rejuvenation strategies. C1 [Soria-Valles, Clara; Osorio, Fernando G.; Gutierrez-Fernandez, Ana; Freije, Jose M. P.; Lopez-Otin, Carlos] Univ Oviedo, Fac Med, Inst Univ Oncol, Dept Bioquim & Biol Mol, E-33006 Oviedo, Spain. [De Los Angeles, Alejandro; Daley, George Q.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [De Los Angeles, Alejandro; Daley, George Q.] Harvard Univ, Sch Med, Boston Childrens Hosp, Harvard Stem Cell Inst,Div Hematol Oncol, Boston, MA 02115 USA. [Bueno, Clara; Menendez, Pablo] Univ Barcelona, Cell Therapy Program, Josep Carreras Leukemia Res Inst, Fac Med, E-08036 Barcelona, Spain. [Menendez, Pablo] ICREA, Barcelona 08035, Spain. [Martin-Subero, Jose I.] Univ Barcelona, Dept Anat Patol Farmacol & Microbiol, IDIBAPS, E-08036 Barcelona, Spain. [Daley, George Q.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Daley, George Q.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Daley, George Q.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Freije, JMP (reprint author), Univ Oviedo, Fac Med, Inst Univ Oncol, Dept Bioquim & Biol Mol, E-33006 Oviedo, Spain. EM jmpf@uniovi.es; clo@uniovi.es RI Lopez-Otin, Carlos/C-6657-2013; Freije, Jose M.P./A-6535-2008; OI Lopez-Otin, Carlos/0000-0001-6964-1904; Freije, Jose M.P./0000-0002-4688-8266; Menendez, Pablo/0000-0001-9372-1007; Martin-Subero, Jose Ignacio/0000-0001-8809-5195 FU Ministerio de Economia y Competitividad-Spain; Gobierno del Principado de Asturias; Instituto de Salud Carlos III (RTICC), Spain; Fundacion Bancaria Caja de Ahorros de Asturias; ISCIII-FIS; Banco Santander through its Santander Universities Global Division FX We thank R. M. Schmid, H. Algul, T. Scholer, A. R. Folgueras, X. S. Puente, A. A. Ferrando, M. Serrano, H. Li, A. Lopez-Soto, C. Barcena, M. Gupta and D. Robinton for helpful comments and advice. We also thank F. Rodriguez and M. Roldon for excellent technical assistance, and the Servicio de Histopatologia (IUOPA) for histological studies. This work was supported by grants from Ministerio de Economia y Competitividad-Spain (to C. L.-O., P. M. and C.B.), Gobierno del Principado de Asturias and Instituto de Salud Carlos III (RTICC), Spain. The Instituto Universitario de Oncologia is supported by Fundacion Bancaria Caja de Ahorros de Asturias. C.B. is a recipient of a 'Miguel Servet' fellowship from the ISCIII-FIS. P.M. is a member of the Spanish Cell Therapy Network (Tercel). C.L.-O. is an Investigator of the Botin Foundation supported by Banco Santander through its Santander Universities Global Division. This paper is dedicated to the memory of Nestor M.O. NR 59 TC 24 Z9 24 U1 1 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 EI 1476-4679 J9 NAT CELL BIOL JI Nat. Cell Biol. PD AUG PY 2015 VL 17 IS 8 BP 1004 EP U320 DI 10.1038/ncb3207 PG 26 WC Cell Biology SC Cell Biology GA CO0NE UT WOS:000358847700008 PM 26214134 ER PT J AU Kelemen, LE Lawrenson, K Tyrer, J Li, Q Lee, JM Seo, JH Phelan, CM Beesley, J Chen, XQ Spindler, TJ Aben, KKH Anton-Culver, H Antonenkova, N Baker, H Bandera, EV Bean, Y Beckmann, MW Bisogna, M Bjorge, L Bogdanova, N Brinton, LA Brooks-Wilson, A Bruinsma, F Butzow, R Campbell, IG Carty, K Chang-Claude, J Chen, YA Chen, ZH Cook, LS Cramer, DW Cunningham, JM Cybulski, C Dansonka-Mieszkowska, A Dennis, J Dicks, E Doherty, JA Dicks, E Doherty, JA Dork, T du Bois, A Durst, M Eccles, D Easton, DT Edwards, RP Eilber, U Ekici, AB Engelholm, SA Fasching, PA Fridley, BL Gao, YT Gentry-Maharaj, A Giles, GG Glasspool, R Goode, EL Goodman, MT Grownwald, J Harrington, P Harter, P Hasmad, HN Hein, A Heitz, F Hildebrandt, MAT Hillemanns, P Hogdall, E Hogdall, C Hosono, S Iversen, ES Jakubowska, A Jensen, A Ji, BT Karlan, BY Kellar, M Kelley, JL Kiemeney, LA Krakstad, C Kjaer, SK Kupryjanczyk, J Lambrechts, D Lambrechts, S Le, ND Lee, AW Lele, S Leminen, A Lester, J Levine, DA Liang, D Lissowska, J Lu, KR Lubinski, J Lundvall, L Massuger, LFAG Matsuo, K McGuire, V McLaughlin, JR McNeish, I Menon, U Modugno, F Moes-Sosnowska, J Moysich, KB Narod, SA Nedergaard, L Ness, RB Nevanlinna, H Adenan, NAM Odunsi, K Olson, SH Orlow, I Orsulic, S Weber, RP Paul, J Pearce, CL Pejovic, T Pelttari, LM Permuth-Wey, J Pike, MC Poole, EM Ramus, SJ Risch, HA Rosen, B Rossing, MA Rothstein, JH Rudolph, A Runnebaum, IB Rzepecka, IK Salvesen, HB Schildkraut, JM Schwaab, I Shu, XO Shvetsov, YB Siddiqui, N Sieh, W Song, HL Southey, MC Sucheston, L Tangen, IL Teo, SH Terry, KL Thompson, PJ Tworoger, SS van Altena, AM Van Nieuwenhuysen, E Vergote, I Vierkant, RA Wang-Gohrke, S Walsh, C Wentzensen, N Whittemore, AS Wicklund, KG Wilkens, LR Sawicki, W Woo, YL Wu, XF Wu, AH Yang, H Zheng, W Ziogas, A Sellers, TA Freedman, ML Chenevix-Trench, G Pharoah, PDP Gayther, SA Berchuck, A AF Kelemen, Linda E. Lawrenson, Kate Tyrer, Jonathan Li, Qiyuan Lee, Janet M. Seo, Ji-Heui Phelan, Catherine M. Beesley, Jonathan Chen, Xiaoqing Spindler, Tassja J. Aben, Katja K. H. Anton-Culver, Hoda Antonenkova, Natalia Baker, Helen Bandera, Elisa V. Bean, Yukie Beckmann, Matthias W. Bisogna, Maria Bjorge, Line Bogdanova, Natalia Brinton, Louise A. Brooks-Wilson, Angela Bruinsma, Fiona Butzow, Ralf Campbell, Ian G. Carty, Karen Chang-Claude, Jenny Chen, Y. Ann Chen, Zhihua Cook, Linda S. Cramer, Daniel W. Cunningham, Julie M. Cybulski, Cezary Dansonka-Mieszkowska, Agnieszka Dennis, Joe Dicks, Ed Doherty, Jennifer A. Dicks, Ed Doherty, Jennifer A. Doerk, Thilo du Bois, Andreas Duerst, Matthias Eccles, Diana Easton, Douglas T. Edwards, Robert P. Eilber, Ursula Ekici, Arif B. Engelholm, Svend Aage Fasching, Peter A. Fridley, Brooke L. Gao, Yu-Tang Gentry-Maharaj, Aleksandra Giles, Graham G. Glasspool, Rosalind Goode, Ellen L. Goodman, Marc T. Grownwald, Jacek Harrington, Patricia Harter, Philipp Hasmad, Hanis Nazihah Hein, Alexander Heitz, Florian Hildebrandt, Michelle A. T. Hillemanns, Peter Hogdall, Estrid Hogdall, Claus Hosono, Satoyo Iversen, Edwin S. Jakubowska, Anna Jensen, Allan Ji, Bu-Tian Karlan, Beth Y. Kellar, Melissa Kelley, Joseph L. Kiemeney, Lambertus A. Krakstad, Camilla Kjaer, Susanne K. Kupryjanczyk, Jolanta Lambrechts, Diether Lambrechts, Sandrina Le, Nhu D. Lee, Alice W. Lele, Shashi Leminen, Arto Lester, Jenny Levine, Douglas A. Liang, Dong Lissowska, Jolanta Lu, Karen Lubinski, Jan Lundvall, Lene Massuger, Leon F. A. G. Matsuo, Keitaro McGuire, Valerie McLaughlin, John R. McNeish, Iain Menon, Usha Modugno, Francesmary Moes-Sosnowska, Joanna Moysich, Kirsten B. Narod, Steven A. Nedergaard, Lotte Ness, Roberta B. Nevanlinna, Heli Adenan, Noor Azmi Mat Odunsi, Kunle Olson, Sara H. Orlow, Irene Orsulic, Sandra Weber, Rachel Palmieri Paul, James Pearce, Celeste Leigh Pejovic, Tanja Pelttari, Liisa M. Permuth-Wey, Jennifer Pike, Malcolm C. Poole, Elizabeth M. Ramus, Susan J. Risch, Harvey A. Rosen, Barry Rossing, Mary Anne Rothstein, Joseph H. Rudolph, Anja Runnebaum, Ingo B. Rzepecka, Iwona K. Salvesen, Helga B. Schildkraut, Joellen M. Schwaab, Ira Shu, Xiao-Ou Shvetsov, Yurii B. Siddiqui, Nadeem Sieh, Weiva Song, Honglin Southey, Melissa C. Sucheston, Lara Tangen, Ingvild L. Teo, Soo-Hwang Terry, Kathryn L. Thompson, Pamela J. Tworoger, Shelley S. van Altena, Anne M. Van Nieuwenhuysen, Els Vergote, Ignace Vierkant, Robert A. Wang-Gohrke, Shan Walsh, Christine Wentzensen, Nicolas Whittemore, Alice S. Wicklund, Kristine G. Wilkens, Lynne R. Sawicki, Wlodzimierz Woo, Yin-Ling Wu, Xifeng Wu, Anna H. Yang, Hannah Zheng, Wei Ziogas, Argyrios Sellers, Thomas A. Freedman, Matthew L. Chenevix-Trench, Georgia Pharoah, Paul D. P. Gayther, Simon A. Berchuck, Andrew CA Australian Canc Study Australian Ovarian Canc Study Grp Ovarian Canc Assoc Consortium TI Genome-wide significant risk associations for mucinous ovarian carcinoma SO NATURE GENETICS LA English DT Article ID IDENTIFIES SUSCEPTIBILITY LOCI; BREAST-CANCER RISK; COLORECTAL-CANCER; MOLECULAR CHARACTERIZATION; ANALYSES REVEAL; FALLOPIAN-TUBE; HEPATITIS-C; CELL-TYPE; TUMORS; GENES AB Genome-wide association studies have identified several risk associations for ovarian carcinomas but not for mucinous ovarian carcinomas (MOCs). Our analysis of 1,644 MOC cases and 21,693 controls with imputation identified 3 new risk associations: rs752590 at 2q13 (P = 3.3 x 10(-8)), rs711830 at 2q31.1 (P = 7.5 x 10(-12)) and rs688187 at 19q13.2 (P = 6.8 x 10(-13)). We identified significant expression quantitative trait locus (eQTL) associations for HOXD9 at 2q31.1 in ovarian (P = 4.95 x 10(-4), false discovery rate (FDR) = 0.003) and colorectal (P = 0.01, FDR = 0.09) tumors and for PAX8 at 2q13 in colorectal tumors (P = 0.03, FDR = 0.09). Chromosome conformation capture analysis identified interactions between the HOXD9 promoter and risk-associated SNPs at 2q31.1. Overexpressing HOXD9 in MOC cells augmented the neoplastic phenotype. These findings provide the first evidence for MOC susceptibility variants and insights into the underlying biology of the disease. C1 [Kelemen, Linda E.] Med Univ S Carolina, Coll Med, Dept Publ Hlth Sci, Charleston, SC 29425 USA. [Lawrenson, Kate; Lee, Janet M.; Spindler, Tassja J.; Lee, Alice W.; Pearce, Celeste Leigh; Pike, Malcolm C.; Ramus, Susan J.; Wu, Anna H.; Gayther, Simon A.] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA. [Tyrer, Jonathan; Harrington, Patricia; Song, Honglin; Pharoah, Paul D. P.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England. [Li, Qiyuan] Xiamen Univ, Coll Med, Xiamen, Peoples R China. [Li, Qiyuan; Seo, Ji-Heui; Freedman, Matthew L.] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Dept Med Oncol, Boston, MA 02115 USA. [Phelan, Catherine M.; Permuth-Wey, Jennifer; Sellers, Thomas A.] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA. [Beesley, Jonathan; Chen, Xiaoqing; Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Dept Canc Genet, Brisbane, Qld, Australia. [Aben, Katja K. H.; Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Hlth Evidence, NL-6525 ED Nijmegen, Netherlands. [Aben, Katja K. H.] Comprehens Canc Ctr Netherlands, Utrecht, Netherlands. [Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Sch Med, Genet Epidemiol Res Inst, Dept Epidemiol, Irvine, CA 92717 USA. 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[Bjorge, Line; Krakstad, Camilla; Salvesen, Helga B.; Tangen, Ingvild L.] Haukeland Hosp, Dept Gynecol & Obstet, N-5021 Bergen, Norway. [Bjorge, Line; Krakstad, Camilla; Salvesen, Helga B.; Tangen, Ingvild L.] Univ Bergen, Dept Clin Sci, Ctr Canc Biomarkers, Bergen, Norway. [Bogdanova, Natalia; Doerk, Thilo] Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany. [Brinton, Louise A.; Ji, Bu-Tian; Wentzensen, Nicolas; Yang, Hannah] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Brooks-Wilson, Angela] British Columbia Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada. [Brooks-Wilson, Angela] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada. [Bruinsma, Fiona; Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Australia. [Butzow, Ralf] Univ Helsinki, Dept Pathol, Helsinki, Finland. [Butzow, Ralf; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M.] Helsinki Univ Hosp, Helsinki, Finland. [Butzow, Ralf; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M.] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland. [Campbell, Ian G.] Peter MacCallum Canc Ctr, Div Res, Canc Genet Lab, East Melbourne, Vic, Australia. [Campbell, Ian G.; Southey, Melissa C.] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia. [Campbell, Ian G.] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia. [Carty, Karen; Glasspool, Rosalind; Paul, James] Beatson West Scotland Canc Ctr, Canc Res UK Clin Trials Unit, Glasgow, Lanark, Scotland. [Chang-Claude, Jenny; Eilber, Ursula; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Chen, Y. Ann; Chen, Zhihua] H Lee Moffitt Canc Ctr & Res Inst, Dept Biostat, Tampa, FL USA. [Cook, Linda S.] Univ New Mexico, Dept Internal Med, Div Epidemiol & Biostat, Albuquerque, NM 87131 USA. [Cramer, Daniel W.; Poole, Elizabeth M.; Terry, Kathryn L.; Tworoger, Shelley S.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Cramer, Daniel W.; Terry, Kathryn L.] Brigham & Womens Hosp, Obstetr & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. [Cunningham, Julie M.] Mayo Clin, Dept Lab Med & Pathol, Div Expt Pathol, Rochester, MN USA. [Cybulski, Cezary; Grownwald, Jacek; Jakubowska, Anna; Lubinski, Jan] West Pomeranian Univ Technol, Int Hereditary Canc Ctr, Dept Genet & Pathol, PL-70310 Szczecin, Poland. [Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta; Moes-Sosnowska, Joanna; Rzepecka, Iwona K.] Maria Sklodowska Curie Mem Canc Ctr & Inst Oncol, Dept Pathol & Lab Diagnost, Warsaw, Poland. [Doherty, Jennifer A.] Geisel Sch Med, Dept Epidemiol, Lebanon, NH USA. [du Bois, Andreas; Harter, Philipp; Heitz, Florian] Kliniken Essen Mitte Evang Huyssens Stiftung Knap, Dept Gynecol & Gynecol Oncol, Essen, Germany. [du Bois, Andreas; Harter, Philipp; Heitz, Florian] Dr Horst Schmidt Kliniken Wiesbaden, Dept Gynecol & Gynecol Oncol, Wiesbaden, Germany. [Duerst, Matthias; Runnebaum, Ingo B.] Univ Jena, Jena Univ Hospital, Dept Gynecol, Jena, Germany. [Eccles, Diana] Univ Southampton, Fac Med, Southampton SO9 5NH, Hants, England. [Edwards, Robert P.; Kelley, Joseph L.; Modugno, Francesmary] Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Div Gynecol Oncol, Pittsburgh, PA USA. [Edwards, Robert P.; Kelley, Joseph L.; Modugno, Francesmary] Univ Pittsburgh, Ovarian Canc Ctr Excellence, Pittsburgh, PA USA. [Ekici, Arif B.] Univ Erlangen Nurnberg, Ctr Comprehens Canc, Inst Human Genet, D-91054 Erlangen, Germany. [Engelholm, Svend Aage] Univ Copenhagen, Rigshosp, Dept Radiat Oncol, DK-2100 Copenhagen, Denmark. [Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. [Fridley, Brooke L.] Univ Kansas, Med Ctr, Dept Biostat, Kansas City, KS 66103 USA. [Gao, Yu-Tang] Shanghai Canc Inst, Shanghai, Peoples R China. [Gentry-Maharaj, Aleksandra; Menon, Usha] UCL, Inst Womens Hlth, Gynaecol Canc Res Ctr, Dept Womens Canc, London, England. [Giles, Graham G.] Univ Melbourne, Ctr Biostat & Epidemiol, Melbourne, Vic, Australia. [Giles, Graham G.] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia. [Goode, Ellen L.] Mayo Clin, Dept Hlth Sci Res, Div Epidemiol, Rochester, MN USA. [Goodman, Marc T.; Thompson, Pamela J.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Canc Prevent & Control, Los Angeles, CA 90048 USA. [Goodman, Marc T.; Thompson, Pamela J.] Cedars Sinai Med Ctr, Community & Populat Hlth Res Inst, Dept Biomed Sci, Los Angeles, CA 90048 USA. [Hasmad, Hanis Nazihah; Teo, Soo-Hwang] Canc Res Initiat Fdn, Sime Darby Med Ctr, Subang Jaya, Malaysia. [Hildebrandt, Michelle A. T.; Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Hillemanns, Peter] Hannover Med Sch, Clin Obstet & Gynaecol, Hannover, Germany. [Hogdall, Estrid] Univ Copenhagen, Herlev Hosp, Dept Pathol, Copenhagen, Denmark. [Hogdall, Estrid; Jensen, Allan; Kjaer, Susanne K.] Danish Canc Soc Res Ctr, Dept Virus Lifestyle & Genes, Copenhagen, Denmark. [Hogdall, Claus; Kjaer, Susanne K.; Lundvall, Lene; Nedergaard, Lotte] Univ Copenhagen, Rigshosp, Dept Gynaecol, DK-2100 Copenhagen, Denmark. [Hosono, Satoyo] Aichi Canc Ctr Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi, Japan. [Iversen, Edwin S.] Duke Univ, Dept Stat Sci, Durham, NC USA. [Karlan, Beth Y.; Lester, Jenny; Orsulic, Sandra; Walsh, Christine] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA. [Lambrechts, Diether] Univ Leuven, Vesalius Res Ctr, Leuven, Belgium. [Lambrechts, Diether] Univ Leuven, Dept Oncol, Lab Translat Genet, Leuven, Belgium. [Lambrechts, Sandrina; Van Nieuwenhuysen, Els; Vergote, Ignace] Univ Hosp Leuven, Dept Obstet & Gynaecol, Div Gynecol Oncol, Leuven, Belgium. [Lambrechts, Sandrina; Van Nieuwenhuysen, Els; Vergote, Ignace] Univ Hosp Leuven, Leuven Canc Inst, Leuven, Belgium. [Le, Nhu D.] British Columbia Canc Agcy, Canc Control Res, Vancouver, BC V5Z 4E6, Canada. [Lele, Shashi; Moysich, Kirsten B.; Sucheston, Lara] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [Liang, Dong] Texas So Univ, Coll Pharm & Hlth Sci, Houston, TX 77004 USA. [Lissowska, Jolanta] Maria Sklodowska Curie Mem Canc Ctr & Inst Oncol, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Lu, Karen] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. [Massuger, Leon F. A. G.; van Altena, Anne M.] Radboud Univ Nijmegen, Med Ctr, Dept Obstet & Gynecol, NL-6525 ED Nijmegen, Netherlands. [Matsuo, Keitaro; Rothstein, Joseph H.] Kyushu Univ, Fac Med Sci, Dept Prevent Med, Nagoya, Aichi, Japan. [McGuire, Valerie; Sieh, Weiva; Whittemore, Alice S.] Stanford Univ, Sch Med, Dept Hlth Res & Policy Epidemiol, Stanford, CA 94305 USA. [McLaughlin, John R.] Publ Hlth Ontario, Toronto, ON, Canada. [McNeish, Iain] Univ Glasgow, Wolfson Wohl Canc Res Ctr, Beatson Inst Canc Res, Inst Canc Sci, Glasgow, Lanark, Scotland. [Modugno, Francesmary] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Modugno, Francesmary] Magee Womens Res Inst, Womens Canc Res Program, Pittsburgh, PA USA. [Modugno, Francesmary] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Narod, Steven A.] Univ Toronto, Womens Coll Res Inst, Toronto, ON, Canada. [Ness, Roberta B.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. [Adenan, Noor Azmi Mat; Woo, Yin-Ling] Univ Malaya, Med Ctr, Dept Obstet & Gynaecol, Kuala Lumpur, Malaysia. [Odunsi, Kunle] Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA. [Olson, Sara H.; Orlow, Irene; Pike, Malcolm C.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Weber, Rachel Palmieri; Schildkraut, Joellen M.] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC USA. [Pearce, Celeste Leigh] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Poole, Elizabeth M.; Tworoger, Shelley S.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Poole, Elizabeth M.; Tworoger, Shelley S.] Harvard Univ, Sch Med, Boston, MA USA. [Risch, Harvey A.] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT USA. [Rosen, Barry] Univ Toronto, Dept Obstet & Gynecol, Toronto, ON, Canada. [Rossing, Mary Anne; Wicklund, Kristine G.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98104 USA. [Rossing, Mary Anne] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Schildkraut, Joellen M.] Duke Canc Inst, Durham, NC USA. [Schwaab, Ira] Praxis Humangenet, Wiesbaden, Germany. [Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Dept Med,Div Epidemiol, Nashville, TN 37212 USA. [Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA. [Shvetsov, Yurii B.; Wilkens, Lynne R.] Univ Hawaii, Ctr Canc, Canc Epidemiol Program, Honolulu, HI 96822 USA. [Siddiqui, Nadeem] Glasgow Royal Infirm, Dept Gynaecol Oncol, Glasgow G4 0SF, Lanark, Scotland. [Teo, Soo-Hwang; Woo, Yin-Ling] Univ Malaya, Fac Med, Med Ctr, Canc Res Inst, Kuala Lumpur, Malaysia. [Vierkant, Robert A.] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN USA. [Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynecol, D-89069 Ulm, Germany. [Sawicki, Wlodzimierz] Med Univ Warsaw, Fac Med 2, Dept Obstet Gynecol & Oncol, Warsaw, Poland. [Berchuck, Andrew] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. RP Gayther, SA (reprint author), Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA. EM simon.gayther@med.usc.edu RI salvesen, Helga/C-1187-2017; Bowtell, David/H-1007-2016; Woo, Yin Ling/B-5198-2010; Bjorge, Line/C-1307-2017; Hein, Alexander/F-6999-2010; Massuger, Leon/H-8072-2014; Kiemeney, Lambertus/D-3357-2009; Brooks-Wilson, Angela/E-9399-2012; van Altena, Anne/B-9824-2016; Dork, Thilo/J-8620-2012; Teo, Soo-hwang/H-2353-2014; Aben, Katja/G-9686-2016 OI salvesen, Helga/0000-0002-4438-8831; Glasspool, Rosalind/0000-0002-5000-1680; Kjaer, Susanne/0000-0002-8347-1398; Ramus, Susan/0000-0003-0005-7798; McNeish, Iain/0000-0002-9387-7586; Orlow, Irene/0000-0001-6234-6961; Krakstad, Camilla/0000-0002-0174-8139; Giles, Graham/0000-0003-4946-9099; Matsuo, Keitaro/0000-0003-1761-6314; Bowtell, David/0000-0001-9089-7525; Woo, Yin Ling/0000-0003-1742-1066; Bjorge, Line/0000-0002-0240-2770; Hein, Alexander/0000-0003-2601-3398; Kiemeney, Lambertus/0000-0002-2368-1326; Brooks-Wilson, Angela/0000-0003-1009-6408; Aben, Katja/0000-0002-0214-2147 FU European Commission [223175-HEALTH-F2-2009-223175]; Ovarian Cancer Research Fund [PPD/RPCI.07]; Genetic Associations and Mechanisms in Oncology (GAME-ON); National Cancer Institute Cancer Post-GWAS Initiative [U19-CA148112]; Wellcome Trust [076113] FX We thank all the individuals who took part in this study and all the researchers, clinicians, and technical and administrative staff who made possible the many studies contributing to this work (a full list is provided in the Supplementary Note). The COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement 223175-HEALTH-F2-2009-223175). The Ovarian Cancer Association Consortium (OCAC) is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific development and funding for this project were supported in part by Genetic Associations and Mechanisms in Oncology (GAME-ON) and a National Cancer Institute Cancer Post-GWAS Initiative (U19-CA148112). Details of the funding of individual investigators and studies are provided in the Supplementary Note. This study made use of data generated by the Wellcome Trust Case Control Consortium; funding for the project was provided by the Wellcome Trust under award 076113. A full list of the investigators who contributed to the generation of the data is available from the consortium website (see URLs). The results published here are based in part on data generated by The Cancer Genome Atlas (TCGA) Pilot Project established by the National Cancer Institute and National Human Genome Research Institute; information about TCGA and the investigators and institutions who constitute the TCGA research network can be found on the project website (see URLs). NR 71 TC 8 Z9 8 U1 3 U2 25 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD AUG PY 2015 VL 47 IS 8 BP 888 EP 897 DI 10.1038/ng.3336 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA CN8FG UT WOS:000358674100012 PM 26075790 ER PT J AU Childs, EJ Mocci, E Campa, D Bracci, PM Gallinger, S Goggins, M Li, DH Neale, RE Olson, SH Scelo, G Amundadottir, LT Bamlet, WR Bijlsma, MF Blackford, A Borges, M Brennan, P Brenner, H Bueno-de-Mesquita, HB Canzian, F Capurso, G Cavestro, GM Chaffee, KG Chanock, SJ Cleary, SP Cotterchio, M Foretova, L Fuchs, C Funel, N Gazouli, M Hassan, M Herman, JM Holcatova, I Holly, EA Hoover, RN Hung, RJ Janout, V Key, TJ Kupcinskas, J Kurtz, RC Landi, S Lu, LG Malecka-Panas, E Mambrini, A Mohelnikova-Duchonova, B Neoptolemos, JP Oberg, AL Orlow, I Pasquali, C Pezzilli, R Rizzato, C Saldia, A Scarpa, A Stolzenberg-Solomon, RZ Strobel, O Tavano, F Vashist, YK Vodicka, P Wolpin, BM Yu, H Petersen, GM Risch, HA Klein, AP AF Childs, Erica J. Mocci, Evelina Campa, Daniele Bracci, Paige M. Gallinger, Steven Goggins, Michael Li, Donghui Neale, Rachel E. Olson, Sara H. Scelo, Ghislaine Amundadottir, Laufey T. Bamlet, William R. Bijlsma, Maarten F. Blackford, Amanda Borges, Michael Brennan, Paul Brenner, Hermann Bueno-de-Mesquita, H. Bas Canzian, Federico Capurso, Gabriele Cavestro, Giulia M. Chaffee, Kari G. Chanock, Stephen J. Cleary, Sean P. Cotterchio, Michelle Foretova, Lenka Fuchs, Charles Funel, Niccola Gazouli, Maria Hassan, Manal Herman, Joseph M. Holcatova, Ivana Holly, Elizabeth A. Hoover, Robert N. Hung, Rayjean J. Janout, Vladimir Key, Timothy J. Kupcinskas, Juozas Kurtz, Robert C. Landi, Stefano Lu, Lingeng Malecka-Panas, Ewa Mambrini, Andrea Mohelnikova-Duchonova, Beatrice Neoptolemos, John P. Oberg, Ann L. Orlow, Irene Pasquali, Claudio Pezzilli, Raffaele Rizzato, Cosmeri Saldia, Amethyst Scarpa, Aldo Stolzenberg-Solomon, Rachael Z. Strobel, Oliver Tavano, Francesca Vashist, Yogesh K. Vodicka, Pavel Wolpin, Brian M. Yu, Herbert Petersen, Gloria M. Risch, Harvey A. Klein, Alison P. TI Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; GENOTYPE IMPUTATION; LUNG ADENOCARCINOMA; CIGARETTE-SMOKING; GENETIC-VARIATION; ALPHA-GENE; RISK; LOCI; POPULATION; MUTATIONS AB Pancreatic cancer is the fourth leading cause of cancer death in the developed world(1). Both inherited high-penetrance mutations in BRCA2 (ref. 2), ATM(3), PALB2 (ref. 4), BRCA1 (ref. 5), STK11 (ref. 6), CDKN2A(7) and mismatch-repair genes(8) and low-penetrance loci are associated with increased risk(9-12). To identify new risk loci, we performed a genome-wide association study on 9,925 pancreatic cancer cases and 11,569 controls, including 4,164 newly genotyped cases and 3,792 controls in 9 studies from North America, Central Europe and Australia. We identified three newly associated regions: 17q25.1 (LINC00673, rs11655237, odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.19-1.34, P = 1.42 x 10(-14)), 7p13 (SUGCT, rs17688601, OR = 0.88, 95% CI = 0.84-0.92, P = 1.41 x 10(-8)) and 3q29 (TP63, rs9854771, OR = 0.89, 95% CI = 0.85-0.93, P = 2.35 x 10(-8)). We detected significant association at 2p13.3 (ETAA1, rs1486134, OR = 1.14, 95% CI = 1.09-1.19, P = 3.36 x 10(-9)), a region with previous suggestive evidence in Han Chinese(12). We replicated previously reported associations at 9q34.2 (ABO)(9), 13q22.1 (KLF5)(10), 5p15.33 (TERT and CLPTM1)(10,11), 13q12.2 (PDX1)(11), 1q32.1 (NR5A2)(10), 7q32.3 (LINC-PINT)(11), 16q23.1 (BCAR1)(11) and 22q12.1 (ZNRF3)(11). Our study identifies new loci associated with pancreatic cancer risk. C1 [Childs, Erica J.] Johns Hopkins Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Mocci, Evelina; Blackford, Amanda; Klein, Alison P.] Sidney Kimmel Comprehens Canc Ctr, Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD 21218 USA. [Campa, Daniele] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Campa, Daniele] Univ Pisa, Dept Biol, Pisa, Italy. [Bracci, Paige M.; Holly, Elizabeth A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Gallinger, Steven; Hung, Rayjean J.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Goggins, Michael; Borges, Michael; Klein, Alison P.] Sol Goldman Pancreat Canc Res Ctr, Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD USA. [Li, Donghui; Hassan, Manal] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. [Neale, Rachel E.] QIMR Berghofer Med Res Inst, Dept Populat Hlth, Kelvin Grove, Qld, Australia. 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Bas] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. [Bueno-de-Mesquita, H. Bas] Univ Malaya, Fac Med, Dept Social & Prevent Med, Kuala Lumpur, Malaysia. [Canzian, Federico; Rizzato, Cosmeri] German Canc Res Ctr, Genom Epidemiol Grp, Heidelberg, Germany. [Capurso, Gabriele] Univ Roma La Sapienza, Digest & Liver Dis Unit, I-00185 Rome, Italy. [Cavestro, Giulia M.] Univ Vita Salute San Raffaele, Milan, Italy. [Cavestro, Giulia M.] IRCCS, Osped San Raffaele, Milan, Italy. [Cleary, Sean P.] Univ Toronto, Dept Surg, Univ Hlth Network, Toronto, ON, Canada. [Cleary, Sean P.] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada. [Cotterchio, Michelle] Univ Toronto, Canc Care Ontario, Toronto, ON, Canada. [Cotterchio, Michelle] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Foretova, Lenka] Masaryk Univ, Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic. [Foretova, Lenka] Masaryk Univ, Fac Med, Brno, Czech Republic. [Fuchs, Charles; Wolpin, Brian M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fuchs, Charles] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Fuchs, Charles; Wolpin, Brian M.] Harvard Univ, Sch Med, Boston, MA USA. [Funel, Niccola] Univ Hosp Pisa, Unit Expt Surg Pathol, Dept Surg, Pisa, Italy. [Gazouli, Maria] Univ Athens, Sch Med, Biol Lab, Dept Med Sci, GR-11527 Athens, Greece. [Herman, Joseph M.] Johns Hopkins Univ, Sch Med, Sol Goldman Pancreat Canc Res Ctr, Dept Radiat Oncol, Baltimore, MD USA. [Holcatova, Ivana] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague, Czech Republic. [Janout, Vladimir] Palacky Univ, Fac Med, Dept Prevent Med, CR-77147 Olomouc, Czech Republic. [Key, Timothy J.] Univ Oxford, Canc Epidemiol Unit, Oxford, England. [Kupcinskas, Juozas] Lithuanian Univ Hlth Sci, Dept Gastroenterol, Kaunas, Lithuania. [Kurtz, Robert C.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Landi, Stefano] Univ Pisa, Genet Sect, Dept Biol, Pisa, Italy. [Lu, Lingeng; Risch, Harvey A.] Yale Univ, Sch Med, Dept Chron Dis Epidemiol, New Haven, CT USA. [Malecka-Panas, Ewa] Med Univ Lodz, Dept Digest Tract Dis, Lodz, Poland. [Mambrini, Andrea] Azienda USL 1 Massa Carrara, Dept Oncol, Massa Carrara, Italy. [Mohelnikova-Duchonova, Beatrice] Inst Publ Hlth, Lab Toxicogen, Prague, Czech Republic. [Neoptolemos, John P.] Univ Liverpool, NIHR, Pancreas Biomed Res Unit, Liverpool Clin Trials Unit, Liverpool L69 3BX, Merseyside, England. [Neoptolemos, John P.] Univ Liverpool, Canc Res UK Clin Trials Unit, Dept Mol & Clin Canc Med, Inst Translat Med, Liverpool L69 3BX, Merseyside, England. [Pasquali, Claudio] Univ Padua, Dept Surg Gastroenterol & Oncol, Padua, Italy. [Pezzilli, Raffaele] St Orsola Malpighi Hosp, Dept Digest Dis, Pancreas Unit, Bologna, Italy. [Scarpa, Aldo] Univ & Hosp Trust Verona, ARC NET Ctr Appl Res Canc, Verona, Italy. [Stolzenberg-Solomon, Rachael Z.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, US Natl Inst Hlth, Rockville, MD USA. [Strobel, Oliver] Univ Heidelberg Hosp, Dept Gen Surg, Heidelberg, Germany. [Tavano, Francesca] IRCCS Sci Inst, Div Gastroenterol & Res Lab, San Giovanni Rotondo, Italy. [Tavano, Francesca] Reg Gen Hosp Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy. [Vashist, Yogesh K.] Univ Med Ctr Hamburg Eppendorf, Dept Gen Visceral & Thorac Surg, Hamburg, Germany. [Vodicka, Pavel] Acad Sci Czech Republic, Inst Expt Med, Dept Mol Biol Canc, Prague, Czech Republic. [Wolpin, Brian M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Yu, Herbert] Univ Hawaii, Ctr Canc, Epidemiol Program, Honolulu, HI 96822 USA. RP Klein, AP (reprint author), Sidney Kimmel Comprehens Canc Ctr, Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD 21218 USA. EM aklein1@jhmi.edu RI Hung, Rayjean/A-7439-2013; Janout, Vladimir/M-5133-2014; Gallinger, Steven/E-4575-2013; Campa, Daniele/K-1617-2016; Tavano, Francesca/K-2203-2016; scarpa, aldo/K-6832-2016; Brenner, Hermann/B-4627-2017; OI Neale, Rachel/0000-0001-7162-0854; Orlow, Irene/0000-0001-6234-6961; Campa, Daniele/0000-0003-3220-9944; Tavano, Francesca/0000-0002-8831-7349; scarpa, aldo/0000-0003-1678-739X; Brenner, Hermann/0000-0002-6129-1572; Funel, Niccola/0000-0002-5028-2363; Landi, Stefano/0000-0001-8364-6357 FU National Cancer Institute/US National Institutes of Health [RO1 CA154823, P30 CA008748]; US National Institutes of Health [HHSN268201100011I]; National Cancer Institute, US National Institutes of Health [R03 CA123546-02]; Ministry of Health of the Czech Republic [NR 9029-4/2006, NR9422-3, NR9998-3, MH CZ-DRO-MMCI 00209805]; National Cancer Institute [P50 CA62924, R01 CA97075]; Mayo Clinic Specialized Programs of Research Excellence (SPORE) in Pancreatic Cancer [P50 CA102701]; Geoffrey Beene Foundation; Arnold and Arlene Goldstein Family Foundation; Society of the Memorial Sloan Kettering Cancer Center; National Health and Medical Research Council of Australia (NHMRC) [442302, 1060183]; US National Institutes of Health/National Cancer Institute [R01 CA1009767, R01 CA109767-S1, 5R01 CA098870]; Joan Rombauer Pancreatic Cancer Fund; California Department of Public Health; National Cancer Institute Surveillance, Epidemiology and End Results (SEER) Program [HHSN261201000140C]; US Centers for Disease Control and Prevention (CDC) National Program of Cancer Registries [U58 DP003862-01]; Czech Science Foundation [P301/12/1734]; Internal Grant Agency of the Czech Ministry of Health [IGA NT 13 263]; Ministry of Research, Science and Arts of Baden-Wurttemberg state; Heidelberger EPZ Pancobank [01GS08114]; BMBH [01EY1101]; Dutch Cancer Society project [2012-5607]; Academic Medical Center Foundation; Italian government; Italian Ministry of Health [RC1203GA57, RC1303GA53, RC1303GA54, RC1303GA50]; Italian Association for Research on Cancer [AIRC 12182]; Italian Ministry of Research [FIRB-RBAP10AHJB]; Italian FIMP-Ministry of Health [CUP_J33G13000210001]; National Institute for Health Research (NIHR) Liverpool Pancreas Biomedical Research Unit, UK FX This work was supported by National Cancer Institute/US National Institutes of Health grant RO1 CA154823. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the US National Institutes of Health to the Johns Hopkins University, contract HHSN268201100011I.; The IARC/Central Europe study was supported by a grant from the National Cancer Institute, US National Institutes of Health (R03 CA123546-02) and by grants from the Ministry of Health of the Czech Republic (NR 9029-4/2006, NR9422-3, NR9998-3 and MH CZ-DRO-MMCI 00209805).; The work at Johns Hopkins University was supported by National Cancer Institute grants P50 CA62924 and R01 CA97075. Additional support was provided by Susan Wojcicki and Dennis Troper.; The Mayo Clinic Molecular Epidemiology of Pancreatic Cancer study is supported by the Mayo Clinic Specialized Programs of Research Excellence (SPORE) in Pancreatic Cancer (P50 CA102701).; The Memorial Sloan Kettering Cancer Center Pancreatic Tumor Registry is supported by National Cancer Institute/US National Institutes of Health grant P30 CA008748, the Geoffrey Beene Foundation, the Arnold and Arlene Goldstein Family Foundation and the Society of the Memorial Sloan Kettering Cancer Center.; The Queensland Pancreatic Cancer Study was supported by a grant from the National Health and Medical Research Council of Australia (NHMRC; grant 442302). R.E.N. is supported by an NHMRC Senior Research Fellowship (1060183).; The University of California San Francisco (UCSF) pancreas study was supported by US National Institutes of Health/National Cancer Institute grants (R01 CA1009767 and R01 CA109767-S1) and the Joan Rombauer Pancreatic Cancer Fund. Collection of cancer incidence data was supported by the California Department of Public Health as part of the statewide cancer reporting program; the National Cancer Institute Surveillance, Epidemiology and End Results (SEER) Program under contract HHSN261201000140C awarded to the Cancer Prevention Institute of California (CPIC); and the US Centers for Disease Control and Prevention (CDC) National Program of Cancer Registries, under agreement U58 DP003862-01 awarded to the California Department of Public Health.; The Yale (Connecticut) pancreas study is supported by US National Institutes of Health/National Cancer Institute grant 5R01 CA098870. The cooperation of 30 Connecticut hospitals, including Stamford Hospital, in allowing patient access is gratefully acknowledged. The Connecticut Pancreas Cancer Study was approved by the Department of Public Health Human Investigation Committee of the state of Connecticut. Certain data used in that study were obtained from the Connecticut Tumor Registry in the Connecticut Department of Public Health. The authors assume full responsibility for analyses and interpretation of these data.; Studies included in PANDoRA were partly funded by the Czech Science Foundation (P301/12/1734) and the Internal Grant Agency of the Czech Ministry of Health (IGA NT 13 263); the Ministry of Research, Science and Arts of Baden-Wurttemberg state (H.B.), the Heidelberger EPZ Pancobank (M.W. Buchler and team; T. Hackert, N.A. Giese, Ch. Tjaden, E. Soyka and M. Meinhardt; Heidelberger Stiftung Chirurgie and BMBF, grant 01GS08114), the BMBH (P. Schirmacher; BMBF grant 01EY1101), Dutch Cancer Society project grant 2012-5607 and the Academic Medical Center Foundation (M.F.B.), the "5x1000" voluntary contribution of the Italian government, the Italian Ministry of Health (RC1203GA57, RC1303GA53, RC1303GA54 and RC1303GA50), the Italian Association for Research on Cancer (A. Scarpa; AIRC 12182), the Italian Ministry of Research (A. Scarpa; FIRB-RBAP10AHJB), the Italian FIMP-Ministry of Health (A. Scarpa; CUP_J33G13000210001) and the National Institute for Health Research (NIHR) Liverpool Pancreas Biomedical Research Unit, UK. We would like to acknowledge the contribution of F. Dijk and O. Busch (Academic Medical Center, Amsterdam). NR 64 TC 29 Z9 30 U1 5 U2 32 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD AUG PY 2015 VL 47 IS 8 BP 911 EP + DI 10.1038/ng.3341 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA CN8FG UT WOS:000358674100016 PM 26098869 ER PT J AU Usher, CL Handsaker, RE Esko, T Tuke, MA Weedon, MN Hastie, AR Cao, H Moon, JE Kashin, S Fuchsberger, C Metspalu, A Pato, CN Pato, MT McCarthy, MI Boehnke, M Altshuler, DM Frayling, TM Hirschhorn, JN McCarroll, SA AF Usher, Christina L. Handsaker, Robert E. Esko, Tonu Tuke, Marcus A. Weedon, Michael N. Hastie, Alex R. Cao, Han Moon, Jennifer E. Kashin, Seva Fuchsberger, Christian Metspalu, Andres Pato, Carlos N. Pato, Michele T. McCarthy, Mark I. Boehnke, Michael Altshuler, David M. Frayling, Timothy M. Hirschhorn, Joel N. McCarroll, Steven A. TI Structural forms of the human amylase locus and their relationships to SNPs, haplotypes and obesity SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; COPY NUMBER VARIATION; BODY-MASS INDEX; MULTIGENE FAMILY; GENETIC ARCHITECTURE; EVOLUTION; VARIANTS; DISEASE; TRAITS; SUSCEPTIBILITY AB Hundreds of genes reside in structurally complex, poorly understood regions of the human genome(1-3). One such region contains the three amylase genes (AMY2B, AMY2A and AMY1) responsible for digesting starch into sugar. Copy number of AMY1 is reported to be the largest genomic influence on obesity(4), although genome-wide association studies for obesity have found this locus unremarkable. Using whole-genome sequence analysis(3,5), droplet digital PCR6 and genome mapping(7), we identified eight common structural haplotypes of the amylase locus that suggest its mutational history. We found that the AMY1 copy number in an individual's genome is generally even (rather than odd) and partially correlates with nearby SNPs, which do not associate with body mass index (BMI). We measured amylase gene copy number in 1,000 obese or lean Estonians and in 2 other cohorts totaling similar to 3,500 individuals. We had 99% power to detect the lower bound of the reported effects on BMI4, yet found no association. C1 [Usher, Christina L.; Handsaker, Robert E.; Esko, Tonu; Moon, Jennifer E.; Altshuler, David M.; Hirschhorn, Joel N.; McCarroll, Steven A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02139 USA. [Handsaker, Robert E.; Esko, Tonu; Moon, Jennifer E.; Kashin, Seva; Altshuler, David M.; Hirschhorn, Joel N.; McCarroll, Steven A.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Handsaker, Robert E.; Kashin, Seva; McCarroll, Steven A.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Esko, Tonu; Moon, Jennifer E.; Hirschhorn, Joel N.] Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA USA. [Esko, Tonu; Moon, Jennifer E.; Hirschhorn, Joel N.] Boston Childrens Hosp, Div Endocrinol, Boston, MA USA. [Esko, Tonu] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Tuke, Marcus A.; Weedon, Michael N.; Frayling, Timothy M.] Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England. [Hastie, Alex R.; Cao, Han] BioNano Genom, San Diego, CA USA. [Fuchsberger, Christian; Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Fuchsberger, Christian; Boehnke, Michael] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia. [Pato, Carlos N.; Pato, Michele T.] Univ So Calif, Dept Psychiat & Behav Sci, Los Angeles, CA USA. [McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [McCarthy, Mark I.] Churchill Hosp, Biomed Res Ctr, Oxford Natl Inst Hlth Res NIHR, Oxford OX3 7LJ, England. [Altshuler, David M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP McCarroll, SA (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02139 USA. EM joelh@broadinstitute.org; mccarroll@genetics.med.harvard.edu OI Fuchsberger, Christian/0000-0002-5918-8947; Esko, Tonu/0000-0003-1982-6569 FU National Human Genome Research Institute [R01 HG006855]; Estonian Ministry of Science and Education [SF0180142s08]; Development Fund of the University of Tartu (SP1GVARENG); European Regional Development Fund [3.2.0304.11-0312, 313010]; US National Institutes of Health [R01 DK075787, DK062370]; European Research Council [SZ-50371-GLUCOSEGENES]; Wellcome Trust [WT097835MF] FX This work was supported by a grant from the National Human Genome Research Institute (R01 HG006855) to S.A.M. to support C.L.U., R.E.H. and S.A.M. Work by T.E. and A.M. was supported through the Estonian Genome Center of the University of Tartu (EGCUT) by Targeted Financing from the Estonian Ministry of Science and Education (SF0180142s08), the Development Fund of the University of Tartu (SP1GVARENG) and the European Regional Development Fund to the Centre of Excellence in Genomics (3.2.0304.11-0312) and through Framework Programme 7 grant 313010. T.E., A.M. and J.N.H. were further supported by the US National Institutes of Health (R01 DK075787). T.M.F. is supported by European Research Council funding (Framework Programme 7, SZ-50371-GLUCOSEGENES), M.A.T. and M.N.W. are supported by the Wellcome Trust Institutional Strategic Support Award (WT097835MF), and M.B. is supported by US National Institutes of Health grant DK062370. NR 51 TC 25 Z9 25 U1 9 U2 26 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD AUG PY 2015 VL 47 IS 8 BP 921 EP + DI 10.1038/ng.3340 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA CN8FG UT WOS:000358674100018 PM 26098870 ER PT J AU Glenn, DR Lee, K Park, H Weissleder, R Yacoby, A Lukin, MD Lee, H Walsworth, RL Connolly, CB AF Glenn, David R. Lee, Kyungheon Park, Hongkun Weissleder, Ralph Yacoby, Amir Lukin, Mikhail D. Lee, Hakho Walsworth, Ronald L. Connolly, Colin B. TI Single-cell magnetic imaging using a quantum diamond microscope SO NATURE METHODS LA English DT Article ID PROTEIN AB We apply a quantum diamond microscope for detection and imaging of immunomagnetically labeled cells. This instrument uses nitrogen-vacancy (NV) centers in diamond for correlated magnetic and fluorescence imaging. Our device provides single-cell resolution and a field of view (similar to 1 mm(2)) two orders of magnitude larger than that of previous NV imaging technologies, enabling practical applications. To illustrate, we quantified cancer biomarkers expressed by rare tumor cells in a large population of healthy cells. C1 [Glenn, David R.; Walsworth, Ronald L.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA. [Lee, Kyungheon; Weissleder, Ralph; Lee, Hakho] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Park, Hongkun; Yacoby, Amir; Lukin, Mikhail D.; Walsworth, Ronald L.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. [Park, Hongkun] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Park, Hongkun; Walsworth, Ronald L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Connolly, Colin B.] Quantum Diamond Technol Inc, Somerville, MA USA. RP Lee, H (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM hlee@mgh.harvard.edu; rwalsworth@cfa.harvard.edu; cconnolly@quantumdiamondtech.com FU US National Institutes of Health [R01HL113156, U54-CA119349]; US Defense Advanced Research Projects Agency (DARPA) QuASAR program; DARPA SBIR [W31P4Q-13-C-0064] FX The authors thank M.L. McKee for help with electron microscopy, as well as M. Liong and H. Shao for advice on magnetic assay protocols. This work was supported in part by US National Institutes of Health grants R01HL113156 (H.L.) and U54-CA119349 (R.W.) as well as the US Defense Advanced Research Projects Agency (DARPA) QuASAR program and DARPA SBIR contract W31P4Q-13-C-0064. NR 17 TC 19 Z9 19 U1 4 U2 71 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 2015 VL 12 IS 8 BP 736 EP U161 DI 10.1038/NMETH.3449 PG 5 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CN8ZW UT WOS:000358736100015 PM 26098019 ER PT J AU Kong, LJ Tang, JY Little, JP Yu, Y Lammermann, T Lin, CP Germain, RN Cuil, M AF Kong, Lingjie Tang, Jianyong Little, Justin P. Yu, Yang Laemmermann, Tim Lin, Charles P. Germain, Ronald N. Cuil, Meng TI Continuous volumetric imaging via an optical phase-locked ultrasound lens SO NATURE METHODS LA English DT Article ID IN-VIVO; NEURONAL-ACTIVITY; MICROSCOPY; CELLS; LIGHT AB In vivo imaging at high spatiotemporal resolution is key to the understanding of complex biological systems. We integrated an optical phase-locked ultrasound lens into a two-photon fluorescence microscope and achieved microsecond-scale axial scanning, thus enabling volumetric imaging at tens of hertz. We applied this system to multicolor volumetric imaging of processes sensitive to motion artifacts, including calcium dynamics in behaving mouse brain and transient morphology changes and trafficking of immune cells. C1 [Kong, Lingjie; Little, Justin P.; Yu, Yang; Cuil, Meng] Howard Hughes Med Inst, Ashburn, VA 20147 USA. [Tang, Jianyong; Laemmermann, Tim; Germain, Ronald N.] NIAID, NIH, Bethesda, MD 20892 USA. [Lin, Charles P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA. [Lin, Charles P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellm Ctr Photomed, Boston, MA USA. [Lin, Charles P.] Harvard Stem Cell Inst, Cambridge, MA USA. RP Cuil, M (reprint author), Howard Hughes Med Inst, Janelia Res Campus, Ashburn, VA 20147 USA. EM cuirn@janelia.hhmi.org RI Yu, Yang/D-4071-2015; kong, lingjie/G-5822-2012 OI Yu, Yang/0000-0002-4340-430X; kong, lingjie/0000-0003-1974-3245 FU Howard Hughes Medical Institute; Intramural Program of the National Institute of Allergy and Infectious Diseases, US National Institutes of Health (NIH); NIH [P41 E8015903-02S1] FX L.K. and M.C. thank W. Gan and H. Dana for many helpful discussions on cerebral cortex imaging, T.-W. Chen for help on data analysis in the visual cortex experiments, S. Peron and N.-L. Xu (Janelia Research Campus) for providing animals during system calibration, K. Ritola (Janelia Research Campus) for preparing GCaMP6 virus, K. Morris and J. Rouchard for virus injections, J. Liu for help on cluster computing, P. Keller for suggestions on data storage, B.-C. Chen and W. Legant for suggestions on data visualization, V. Iyer for support on ScanImage, D. Milkie for developing the custom Labview program, S. Sawtelle and L. Ramasamy for making the low-noise high-speed comparator, V. Goncharov for testing high-speed photodetectors, J. Freeman and F. Amat for help on data analysis and the Howard Hughes Medical Institute for funding the project. This work was supported in part by the Intramural Program of the National Institute of Allergy and Infectious Diseases, US National Institutes of Health (NIH) (to R.N.G.), and NIH grant P41 E8015903-02S1 (to C.P.L.). NR 27 TC 23 Z9 24 U1 8 U2 33 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 2015 VL 12 IS 8 BP 759 EP U166 DI 10.1038/NMETH.3476 PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CN8ZW UT WOS:000358736100021 PM 26167641 ER PT J AU Reiberger, T Chen, YC Ramjiawan, RR Hato, T Fan, C Samuel, R Roberge, S Huang, PG Lauwers, GY Zhu, AX Bardeesy, N Jain, RK Duda, DG AF Reiberger, Thomas Chen, Yunching Ramjiawan, Rakesh R. Hato, Tai Fan, Christopher Samuel, Rekha Roberge, Sylvie Huang, Peigen Lauwers, Gregory Y. Zhu, Andrew X. Bardeesy, Nabeel Jain, Rakesh K. Duda, Dan G. TI An orthotopic mouse model of hepatocellular carcinoma with underlying liver cirrhosis SO NATURE PROTOCOLS LA English DT Article ID ASTROCYTE ELEVATED GENE-1; FUTURE-DIRECTIONS; MICE; HEPATOCARCINOGENESIS; MICROENVIRONMENT; HEPATOCYTES; SORAFENIB; STRATEGIES; ONCOGENE; INSIGHTS AB Subcutaneous xenografts have been used for decades to study hepatocellular carcinoma (HCC). These models do not reproduce the specific pathophysiological features of HCCs, which occur in cirrhotic livers that show pronounced necroinflammation, abnormal angiogenesis and extensive fibrosis. As these features are crucial for studying the role of the pathologic host microenvironment in tumor initiation, progression and treatment response, alternative HCC models are desirable. Here we describe a syngeneic orthotopic HCC model in immunocompetent mice with liver cirrhosis induced by carbon tetrachloride (CCl4) that recapitulates key features of human HCC. Induction of substantial hepatic fibrosis requires 12 weeks of CCl4 administration. Intrahepatic implantation of mouse HCC cell lines requires 30 min per mouse. Tumor growth varies by tumor cell line and mouse strain used. Alternatively, tumors can be induced in a genetically engineered mouse model. In this setting, CCl4 is administered for 12 weeks after tail-vein injection of Cre-expressing adenovirus (adeno-Cre) in Stk4(-/-)Stk3(F/-) (also known as Mst1(-/-)Mst2(F/-); F indicates a floxed allele) mice, and it results in the development of HCC tumors (hepatocarcinogenesis) concomitantly with liver cirrhosis. C1 [Reiberger, Thomas; Chen, Yunching; Ramjiawan, Rakesh R.; Hato, Tai; Fan, Christopher; Samuel, Rekha; Roberge, Sylvie; Huang, Peigen; Jain, Rakesh K.; Duda, Dan G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Labs Tumor Biol, Boston, MA 02114 USA. [Reiberger, Thomas; Chen, Yunching; Ramjiawan, Rakesh R.; Hato, Tai; Fan, Christopher; Samuel, Rekha; Roberge, Sylvie; Huang, Peigen; Lauwers, Gregory Y.; Zhu, Andrew X.; Bardeesy, Nabeel; Jain, Rakesh K.; Duda, Dan G.] Harvard Univ, Sch Med, Boston, MA USA. [Reiberger, Thomas] Med Univ Vienna, Div Gastroenterol & Hepatol, Vienna, Austria. [Chen, Yunching] Natl Tsing Hua Univ, Inst Biomed Engn, Hsinchu, Taiwan. [Ramjiawan, Rakesh R.] Vrije Univ Amsterdam, Univ Med Ctr, Dept Med Oncol, Angiogenesis Lab,Canc Ctr Amsterdam, Amsterdam, Netherlands. [Fan, Christopher] Duke Univ, Sch Med, Durham, NC USA. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Zhu, Andrew X.; Bardeesy, Nabeel] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Duda, DG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Labs Tumor Biol, Boston, MA 02114 USA. EM gduda@partners.org FU NIH [P01-CA080124]; National Cancer Institute/Proton Beam Federal Share Program awards [R01-CA159258, R21-CA139168, R01-CA126642]; American Cancer Society [120733-RSG-11-073-01-TBG]; Max Kade Fellowship by the Austrian Academy of Science; Erwin-Schroedinger Fellowship by the Austrian Science Funds; Howard Hughes Medical Institute Medical Research Fellowship; Astellas Foundation for Research on Metabolic Disorders FX The authors thank D. Nguyen, A. Pieters and C. Smith for their outstanding support in establishing this protocol. This study was supported by the NIH grant P01-CA080124, and in part by grants R01-CA159258, R21-CA139168, R01-CA126642 and National Cancer Institute/Proton Beam Federal Share Program awards (to D.G.D. and R.K.J.); by the American Cancer Society grant 120733-RSG-11-073-01-TBG (to D.G.D.); by a Max Kade Fellowship by the Austrian Academy of Science and a Erwin-Schroedinger Fellowship by the Austrian Science Funds (to T.R.); by a Howard Hughes Medical Institute Medical Research Fellowship (to C.F.); and by a Postdoctoral Fellowship from Astellas Foundation for Research on Metabolic Disorders (to T.H.). NR 31 TC 4 Z9 4 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 EI 1750-2799 J9 NAT PROTOC JI Nat. Protoc. PD AUG PY 2015 VL 10 IS 8 BP 1264 EP 1274 DI 10.1038/nprot.2015.080 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CN5PV UT WOS:000358482200010 PM 26203823 ER PT J AU Tabassum, DP Polyak, K AF Tabassum, Doris P. Polyak, Kornelia TI Tumorigenesis: it takes a village SO NATURE REVIEWS CANCER LA English DT Review ID CANCER-CELL SUBPOPULATIONS; CIRCULATING TUMOR-CELLS; MOUSE MAMMARY-TUMORS; BREAST-CANCER; DRUG-RESISTANCE; COLORECTAL-CANCER; CLONAL EVOLUTION; ESR1 MUTATIONS; PUBLIC-GOODS; HETEROGENEITY AB Although it is widely accepted that most cancers exhibit some degree of intratumour heterogeneity, we are far from understanding the dynamics that operate among subpopulations within tumours. There is growing evidence that cancer cells behave as communities, and increasing attention is now being directed towards the cooperative behaviour of subclones that can influence disease progression. As expected, these interactions can add a greater layer of complexity to therapeutic interventions in heterogeneous tumours, often leading to a poor prognosis. In this Review, we highlight studies that demonstrate such interactions in cancer and postulate ways to overcome them with better-designed therapeutic strategies. C1 [Tabassum, Doris P.; Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Tabassum, Doris P.] Harvard Univ, Sch Med, BBS Program, Boston, MA 02115 USA. [Polyak, Kornelia] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Polyak, Kornelia] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM Kornelia_Polyak@dfci.harvard.edu FU US Army Congressionally Directed Research [BC131217P1]; Breast Cancer Research Foundation FX The authors thank A. Marusyk and M. Janiszewska for their critical reading of the manuscript and for stimulating discussions. Tumour heterogeneity research in the authors' laboratory is supported by US Army Congressionally Directed Research BC131217P1 (K.P.), and the Breast Cancer Research Foundation (K.P.). NR 90 TC 57 Z9 58 U1 17 U2 78 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X EI 1474-1768 J9 NAT REV CANCER JI Nat. Rev. Cancer PD AUG PY 2015 VL 15 IS 8 BP 473 EP 483 DI 10.1038/nrc3971 PG 11 WC Oncology SC Oncology GA CN5PK UT WOS:000358481100008 PM 26156638 ER PT J AU Walcott, BP Iorgulescu, JB Stapleton, CJ Kamel, H AF Walcott, Brian P. Iorgulescu, J. Bryan Stapleton, Christopher J. Kamel, Hooman TI Incidence, Timing, and Predictors of Delayed Shunting for Hydrocephalus After Aneurysmal Subarachnoid Hemorrhage SO NEUROCRITICAL CARE LA English DT Article DE Aneurysm; Subarachnoid hemorrhage; Hydrocephalus; Cerebrospinal fluid ID CEREBRAL ANEURYSMS; COMMUNICATING HYDROCEPHALUS; DEPENDENT HYDROCEPHALUS; ADMINISTRATIVE DATA; COMPENSATION; DATABASE; TRIAL AB Although hydrocephalus is often treated with permanent cerebrospinal fluid (CSF) shunting during hospitalization for acute aneurysmal subarachnoid hemorrhage (SAH), little is known about the development of delayed hydrocephalus. Using administrative data on all visits to nonfederal emergency departments and acute care hospitals across California from 2005 to 2010, we identified patients with SAH and discharged without placement of a CSF shunt. Patients were followed for up to 7 years to determine whether they subsequently developed delayed hydrocephalus, as indicated by hospitalization for a permanent CSF diversion procedure. In 8,889 patients discharged with SAH, 116 (1.3 %) went on to develop delayed hydrocephalus. Most (> 90 %) diagnoses of delayed hydrocephalus occurred within the first year after discharge. Cox proportional hazards analysis identified microsurgical clipping (hazard ratio 2.0; 95 % confidence interval 1.2-3.3), temporary ventriculostomy placement (2.5; 1.6-4.1), mechanical ventilation (1.7; 1.1-2.8), and discharge to a skilled nursing facility (2.9; 1.8-4.6) as being significantly associated with the development of delayed hydrocephalus. At 1 year after discharge, the cumulative rate of delayed hydrocephalus was 0.9 % (95 % CI, 0.7-1.1 %) for those without temporary ventriculostomy placement during the initial hospitalization, versus 5.7 % (95 % CI, 3.9-8.1 %) in those who had received a temporary ventriculostomy. Delayed hydrocephalus after SAH occurs rarely overall, but in a substantial proportion of patients who required temporary ventriculostomy during the initial hospitalization. These results support vigilant surveillance of patients after removal of a temporary ventriculostomy, given the potential of delayed hydrocephalus to impair recovery or even result in clinical deterioration following SAH. C1 [Walcott, Brian P.; Stapleton, Christopher J.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Walcott, Brian P.; Stapleton, Christopher J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Iorgulescu, J. Bryan; Kamel, Hooman] Weill Cornell Med Coll, Dept Neurol, New York, NY USA. [Iorgulescu, J. Bryan; Kamel, Hooman] Weill Cornell Med Coll, Brain & Mind Res Inst, New York, NY USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White Bldg Room 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu FU Brain Aneurysm Foundation FX The Brain Aneurysm Foundation (B.P.W.) NR 18 TC 3 Z9 3 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 EI 1556-0961 J9 NEUROCRIT CARE JI Neurocrit. Care PD AUG PY 2015 VL 23 IS 1 BP 54 EP 58 DI 10.1007/s12028-014-0072-y PG 5 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA CN8FJ UT WOS:000358674600008 PM 25519720 ER PT J AU Cai, XM Robinson, J Muehlschlegel, S White, DB Holloway, RG Sheth, KN Fraenkel, L Hwang, DY AF Cai, Xuemei Robinson, Jennifer Muehlschlegel, Susanne White, Douglas B. Holloway, Robert G. Sheth, Kevin N. Fraenkel, Liana Hwang, David Y. TI Patient Preferences and Surrogate Decision Making in Neuroscience Intensive Care Units SO NEUROCRITICAL CARE LA English DT Review DE Communication; Shared decision-making; Prognosis; Neurocritical care; Decision aid ID OF-LIFE CARE; FAMILY CONFERENCES; CRITICALLY-ILL; SUBSTITUTED JUDGMENT; ETHICS CONSULTATIONS; CONTROLLED-TRIAL; COMMUNICATION; SUPPORT; ICU; END AB In the neuroscience intensive care unit (NICU), most patients lack the capacity to make their own preferences known. This fact leads to situations where surrogate decision makers must fill the role of the patient in terms of making preference-based treatment decisions, oftentimes in challenging situations where prognosis is uncertain. The neurointensivist has a large responsibility and role to play in this shared decision-making process. This review covers how NICU patient preferences are determined through existing advance care documentation or surrogate decision makers and how the optimum roles of the physician and surrogate decision maker are addressed. We outline the process of reaching a shared decision between family and care team and describe a practice for conducting optimum family meetings based on studies of ICU families in crisis. We review challenges in the decision-making process between surrogate decision makers and medical teams in neurocritical care settings, as well as methods to ameliorate conflicts. Ultimately, the goal of shared decision making is to increase knowledge amongst surrogates and care providers, decrease decisional conflict, promote realistic expectations and preference-centered treatment strategies, and lift the emotional burden on families of neurocritical care patients. C1 [Cai, Xuemei] Massachusetts Gen Hosp, Div Neurocrit Care & Emergency Neurol, Dept Neurol, Boston, MA 02114 USA. [Robinson, Jennifer; Sheth, Kevin N.; Hwang, David Y.] Yale Univ, Sch Med, Dept Neurol, Div Neurocrit Care & Emergency Neurol, New Haven, CT 06510 USA. [Muehlschlegel, Susanne] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA. [Muehlschlegel, Susanne] Univ Massachusetts, Sch Med, Dept Anesthesia Crit Care, Worcester, MA USA. [Muehlschlegel, Susanne] Univ Massachusetts, Sch Med, Dept Surg, Worcester, MA USA. [White, Douglas B.] Univ Pittsburgh, Med Ctr, Dept Crit Care Med, Program Eth & Decis Making Crit Illness, Pittsburgh, PA USA. [Holloway, Robert G.] Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA. [Fraenkel, Liana] Yale Univ, Sch Med, Dept Med, Div Rheumatol, New Haven, CT 06510 USA. RP Cai, XM (reprint author), Massachusetts Gen Hosp, Div Neurocrit Care & Emergency Neurol, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. EM caix@post.harvard.edu FU NIH [5K24AR060231-02, 5P60AR047782, 1R01AG045176-01, 1R01NR014663]; VA Health Services Research IIR; American Brain Foundation Practice Research Training Fellowship FX Liana Fraenkel receives research support from the NIH 5K24AR060231-02, 5P60AR047782, and the VA Health Services Research IIR. David Y. Hwang has received an American Brain Foundation Practice Research Training Fellowship. Douglas B. White receives research support from NIH 1R01AG045176-01 and 1R01NR014663. NR 77 TC 2 Z9 2 U1 2 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 EI 1556-0961 J9 NEUROCRIT CARE JI Neurocrit. Care PD AUG PY 2015 VL 23 IS 1 BP 131 EP 141 DI 10.1007/s12028-015-0149-2 PG 11 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA CN8FJ UT WOS:000358674600020 PM 25990137 ER PT J AU Jensen, KP Herman, AI Morean, ME Kranzler, HR Gelernter, J Sofuoglu, M AF Jensen, K. P. Herman, A. I. Morean, M. E. Kranzler, H. R. Gelernter, J. Sofuoglu, M. TI FKBP5 variation is associated with the acute and chronic effects of nicotine SO PHARMACOGENOMICS JOURNAL LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; CHILDHOOD TRAUMA; GLUCOCORTICOID RESISTANCE; ACETYLCHOLINE-RECEPTOR; INTRAVENOUS NICOTINE; WITHDRAWAL SYMPTOMS; SMOKING ABSTINENCE; NUCLEUS-ACCUMBENS; MAJOR DEPRESSION; DRUG-DEPENDENCE AB Stress and hormones released in response to stress influence the effects of nicotine and the severity of nicotine withdrawal. Here, we systematically examine the contribution of a stress response gene, FKBP5, to the acute and chronic behavioral effects of nicotine in smokers. Subjects were European- and African-American (EA and AA) heavy smokers who participated in an intravenous (IV) nicotine administration study (total n = 169). FKBP5 rs3800373 genotype was analyzed for association to several outcomes, including nicotine withdrawal and the acute subjective, heart rate (HR), blood pressure and plasma cortisol responses to IV nicotine. Nicotine withdrawal was also examined in relation to rs3800373 allele frequencies in an independent cohort of EA and AA current smokers (n = 3821). For a subset of laboratory subjects FKBP5 mRNA (n = 48) expression was explored for an association to the same outcomes. The rs3800373 minor allele was associated with less severe nicotine withdrawal in laboratory subjects and the independent cohort of smokers. The rs3800373 minor allele was also associated with lower subjective ratings of negative drug effects in response to IV nicotine. Low FKBP5 mRNA expression was associated lower cortisol levels, lower subjective ratings of negative drug effects and a blunted HR response to nicotine. Stress hormone regulation via FKBP5 warrants further investigation as a potential contributor to the effects of nicotine withdrawal, which occurs commonly, and has an important role in the maintenance of smoking behavior and relapse following a quit attempt. C1 [Jensen, K. P.; Herman, A. I.; Morean, M. E.; Gelernter, J.; Sofuoglu, M.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Jensen, K. P.; Herman, A. I.; Gelernter, J.; Sofuoglu, M.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Kranzler, H. R.] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Kranzler, H. R.] Philadelphia VA Med Ctr, MIRECC VISN4, Philadelphia, PA USA. [Gelernter, J.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Gelernter, J.] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT USA. RP Jensen, KP (reprint author), Yale Univ, Sch Med, VA Connecticut Healthcare Syst, Dept Psychiat, 950 Campbell Ave, West Haven, CT 06516 USA. EM kevin.jensen@yale.edu FU NIH [R01 AA011330, R01 AA017535, R01 DA030976, R01 DA12690, R03 DA027474, K24 AA013736, K12 DA00167, T32 MH014276, T32 AA015496]; US Department of Veterans Affairs (VA) [575B]; VISN 1 New England Mental Illness Research; Education and Clinical Center (MIRECC); VA National Center for PTSD; VA VISN 1 CDA; VA MERIT; National Institutes of Health [N01-HG-65403] FX This work was supported in part by NIH grants, R01 AA011330, R01 AA017535, R01 DA030976, R01 DA12690, R03 DA027474, K24 AA013736, K12 DA00167, T32 MH014276 and T32 AA015496. This work also received support from the US Department of Veterans Affairs (VA) through Cooperative Study #575B, the VISN 1 New England Mental Illness Research, Education and Clinical Center (MIRECC) and VA National Center for PTSD, and a VA VISN 1 CDA and VA MERIT. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University (contract number N01-HG-65403). NR 54 TC 7 Z9 7 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X EI 1473-1150 J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD AUG PY 2015 VL 15 IS 4 BP 340 EP 346 DI 10.1038/tpj.2014.76 PG 7 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA CN5CY UT WOS:000358448500008 PM 25532758 ER PT J AU Sautter, FJ Glynn, SM Cretu, JB Senturk, D Vaught, AS AF Sautter, Frederic J. Glynn, Shirley M. Cretu, Julia Becker Senturk, Damla Vaught, Amanda S. TI Efficacy of Structured Approach Therapy in Reducing PTSD in Returning Veterans: A Randomized Clinical Trial SO PSYCHOLOGICAL SERVICES LA English DT Article DE couple therapy; posttraumatic stress disorder; returning veterans; behavior therapy; treatment ID POSTTRAUMATIC-STRESS-DISORDER; BEHAVIORAL CONJOINT THERAPY; COGNITIVE-PROCESSING THERAPY; PROLONGED EXPOSURE; COMBAT VETERANS; INTIMATE-RELATIONSHIPS; EMOTION REGULATION; COUPLE ADJUSTMENT; VIETNAM VETERANS; INITIAL FINDINGS AB The U.S. military deployed in support to Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) show high rates of posttraumatic stress disorder (PTSD) and relationship, partner, and parenting distress. Given the pervasive effect of combat-related PTSD on returning veterans and its effect on their loved ones, the investigators have developed a couples-based treatment, structured approach therapy (SAT), to reduce PTSD while simultaneously decreasing relationship and partner distress. This study presents treatment outcome data measuring PTSD and relationship outcomes from a randomized clinical trial (RCT) comparing SAT, a manualized 12-session novel couples-based PTSD treatment, to a manualized 12-session couples-based educational intervention (PTSD Family Education [PFE]). Data were collected from 57 returning veterans meeting Diagnostic and Statistical Manual of Mental Disorders (fourth edition, text revision; DSM-IV-TR) criteria for PTSD and their cohabiting partners; data collection was scheduled for pretreatment, posttreatment, and 3-month follow-up. Findings from an intent-to-treat analysis revealed that veterans receiving SAT showed significantly greater reductions in self-rated (PTSD Checklist; p < .0006) and Clinician-Administered PTSD Scale (CAPS)-rated PTSD (p < .0001) through the 3-month follow-up compared with veterans receiving PFE; 15 of 29 (52%) veterans receiving SAT and 2 of 28 (7%) receiving PFE no longer met DSM-IV-TR criteria for PTSD. Furthermore, SAT was associated with significant improvements in veteran relationship adjustment, attachment avoidance, and state anxiety. Partners showed significant reductions in attachment anxiety. This couples-based treatment for combat-related PTSD appears to have a strong therapeutic effect on combat-related PTSD in recently returned veterans. C1 [Sautter, Frederic J.] Southeast Louisiana Vet Hlth Care Syst, Family Mental Hlth Program, New Orleans, LA USA. [Sautter, Frederic J.] Tulane Univ, Sch Med, Dept Psychiat, New Orleans, LA 70112 USA. [Glynn, Shirley M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Glynn, Shirley M.] UCLA Welcome Back Vet Family Resilience Ctr, Los Angeles, CA USA. [Cretu, Julia Becker] Tulane Univ, Sch Med, Dept Psychiat & Behav Sci, New Orleans, LA 70112 USA. [Cretu, Julia Becker] Southeast Louisiana Vet Hlth Care Syst, Dept Res, New Orleans, LA USA. [Senturk, Damla] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90024 USA. [Senturk, Damla] Univ Calif Los Angeles, Dept Stat, Los Angeles, CA 90024 USA. [Vaught, Amanda S.] Southeast Louisiana Vet Hlth Care Syst, PTSD Clin Team, New Orleans, LA 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 fsautter@tulane.edu FU VA Research Rehabilitation and Development program [B6756R]; South Central Mental Illness Research Education and Clinical Center FX This work was supported in part by a Merit Review grant (B6756R) from the VA Research Rehabilitation and Development program and a Supplemental Funding Award from the South Central Mental Illness Research Education and Clinical Center to Frederic J. Sautter. NR 76 TC 2 Z9 2 U1 2 U2 13 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 2015 VL 12 IS 3 BP 199 EP 212 DI 10.1037/ser0000032 PG 14 WC Psychology, Clinical SC Psychology GA CN8KN UT WOS:000358689300002 PM 26213789 ER PT J AU Vaughn-Coaxum, R Smith, BN Iverson, KM Vogt, D AF Vaughn-Coaxum, Rachel Smith, Brian N. Iverson, Katherine M. Vogt, Dawne TI Family Stressors and Postdeployment Mental Health in Single Versus Partnered Parents Deployed in Support of the Wars in Afghanistan and Iraq SO PSYCHOLOGICAL SERVICES LA English DT Article DE deployment stressors; family structure; mental health; military families; veterans ID NATIONAL-GUARD SOLDIERS; POSTTRAUMATIC-STRESS; MILITARY FAMILIES; PSYCHOMETRIC PROPERTIES; COUPLE ADJUSTMENT; PRIMARY-CARE; RISK-FACTORS; SYMPTOMS; CHILDREN; DEPRESSION AB Little is known about the family-related stress and postdeployment adjustment of single versus partnered parents deployed in support of the wars in Iraq and Afghanistan. This study examined exposure to family-related stressors during and after deployment, as well as postdeployment psychological symptoms in a national sample of 318 single (n = 74) and partnered (n = 244) parent veterans of Operation Enduring Freedom and Operation Iraqi Freedom. Results demonstrated that single parents experienced higher levels of concern about life and family disruptions during deployment, lower levels of social support during and after deployment, and poorer postdeployment family functioning than partnered parents. Single parents also reported higher posttraumatic stress symptom severity, but not depression or anxiety symptom severity, compared with partnered parents. Family-related stressors demonstrated different associations with mental health for single and partnered parents, suggesting that some stressor-symptom relations may be more salient for single parents, and others may be more salient for partnered parents. Findings suggest that the deployment and postdeployment experiences of parents differ based on their partnered status, which has implications for the design and provision of services to single and partnered parents. C1 [Vaughn-Coaxum, Rachel; Smith, Brian N.; Iverson, Katherine M.; Vogt, Dawne] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr Posttraumat Stress Disorder, Boston, MA USA. [Smith, Brian N.; Iverson, Katherine M.; Vogt, Dawne] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. RP Vaughn-Coaxum, R (reprint author), Harvard Univ, Dept Psychol, William James Hall,33 Kirkland St, Cambridge, MA 02128 USA. EM rachelvaughn@fas.harvard.edu FU Department of Veterans Affairs, Health Services Research and Development (HSRD) Service [DHI 09-086]; HSR&D Career Development Award (CDA) [10-029] FX This study was supported by a Department of Veterans Affairs, Health Services Research and Development (HSR&D) Service grant ("Validation of Modified DRRI Scales in a National Sample of OEF/OIF Veterans," Project #DHI 09-086, Dawne Vogt, Principal Investigator). Katherine M. Iverson's contribution to this study was supported by a HSR&D Career Development Award (CDA 10-029). The opinions expressed in this article are the authors' and do not reflect those of the Department of Veterans Affairs. The authors report no financial relationships or interests that may be affected by material in the manuscript, or which might potentially bias it. NR 37 TC 0 Z9 0 U1 6 U2 11 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 2015 VL 12 IS 3 BP 241 EP 249 DI 10.1037/ser0000026 PG 9 WC Psychology, Clinical SC Psychology GA CN8KN UT WOS:000358689300006 PM 26213793 ER PT J AU Price, M Yuen, EK Davidson, TM Hubel, G Ruggiero, KJ AF Price, Matthew Yuen, Erica K. Davidson, Tatiana M. Hubel, Grace Ruggiero, Kenneth J. TI Access and Completion of a Web-based Treatment in a Population-Based Sample of Tornado-Affected Adolescents SO PSYCHOLOGICAL SERVICES LA English DT Article DE adolescents; Internet interventions; traumatic stress; natural disaster ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-BEHAVIORAL TREATMENT; MENTAL-HEALTH INTERVENTION; PSYCHOLOGICAL DISTRESS; RANDOMIZED-TRIALS; HURRICANE-ANDREW; NATIONAL SAMPLE; SYMPTOMS; PREDICTORS; SERVICES AB Although Web-based treatments have significant potential to assess and treat difficult-to-reach populations, such as trauma-exposed adolescents, the extent that such treatments are accessed and used is unclear. The present study evaluated the proportion of adolescents who accessed and completed a Web-based treatment for postdisaster mental health symptoms. Correlates of access and completion were examined. A sample of 2,000 adolescents living in tornado-affected communities was assessed via structured telephone interview and invited to a Web-based treatment. The modular treatment addressed symptoms of posttraumatic stress disorder, depression, and alcohol and tobacco use. Participants were randomized to experimental or control conditions after accessing the site. Overall access for the intervention was 35.8%. Module completion for those who accessed ranged from 52.8% to 85.6%. Adolescents with parents who used the Internet to obtain health-related information were more likely to access the treatment. Adolescent males were less likely to access the treatment. Future work is needed to identify strategies to further increase the reach of Web-based treatments to provide clinical services in a postdisaster context. C1 [Price, Matthew] Univ Vermont, Dept Psychol Sci, Burlington, VT 05405 USA. [Yuen, Erica K.] Univ Tampa, Dept Psychol, Tampa, FL USA. [Davidson, Tatiana M.] Med Univ S Carolina, Coll Nursing, Dept Psychiat & Behav Sci, Natl Crime Victims Res & Treatment Ctr, Charleston, SC USA. [Davidson, Tatiana M.] Med Univ S Carolina, Coll Nursing, Technol Applicat Ctr Healthful Lifestyles, Charleston, SC USA. [Hubel, Grace] Med Univ S Carolina, Dept Psychiat & Behav Sci, Natl Crime Victims Res & Treatment Ctr, Charleston, SC USA. [Ruggiero, Kenneth J.] Ralph H Johnson VA Med Ctr, MUSC Charleston Hlth Equ & Rural Outreach Innovat, Coll Nursing, Technol Applicat Ctr Healthful Lifestyles, Charleston, SC USA. RP Price, M (reprint author), Univ Vermont, Dept Psychol Sci, John Dewey Hall,2 Colchester Ave, Burlington, VT 05405 USA. EM matthew.price@uvm.edu FU NIMH NIH HHS [R01 MH081056] NR 52 TC 1 Z9 1 U1 1 U2 8 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 2015 VL 12 IS 3 BP 283 EP 290 DI 10.1037/ser0000017 PG 8 WC Psychology, Clinical SC Psychology GA CN8KN UT WOS:000358689300011 PM 25622071 ER PT J AU Castro, F AhnAllen, CG Wiltsey-Stirman, S Lester-Williams, K Klunk-Gillis, J Dick, AM Resick, PA AF Castro, Frank AhnAllen, Christopher G. Wiltsey-Stirman, Shannon Lester-Williams, Kristin Klunk-Gillis, Julie Dick, Alexandra M. Resick, Patricia A. TI African American and European American Veterans' Perspectives on Receiving Mental Health Treatment SO PSYCHOLOGICAL SERVICES LA English DT Article DE attitudes; mental health treatment; evidence-based practices; African Americans; veterans ID ETHNIC-MINORITIES; UNITED-STATES; SERVICES; PSYCHOTHERAPY; DISORDERS; CARE; DISSEMINATION; BARRIERS; THERAPY; RACE AB Little is known about client attitudes, especially veterans', toward the types of structured interventions that are increasingly being offered in public sector and U.S. Department of Veterans Affairs mental health clinics, nor is the possible impact these attitudes may have on treatment engagement well understood. Previous work indicates that attitudes of African Americans and European Americans toward treatment may differ in important ways. Attitudes toward treatment have been a proposed explanation for lower treatment engagement and higher dropout rates among African Americans compared with European Americans. Yet to date, the relationship between race and attitudes toward treatment and treatment outcomes has been understudied and the findings inconclusive. The purpose of this study was to explore African American and European American veteran attitudes toward mental health care, especially as they relate to structured treatments. Separate focus groups were conducted with 24 African American and 37 European American military veterans. In general, both groups reported similar reasons for seeking 0treatment and similar thoughts regarding the purpose of therapy. Differences emerged primarily regarding therapist preferences. In both groups, some participants expressed favorable opinions of structured treatments and others expressed negative views; treatment preferences did not appear to be influenced by race. C1 [Castro, Frank] VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Boston, MA USA. [Castro, Frank; Wiltsey-Stirman, Shannon] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Castro, Frank] Harbor Healthcare Syst, Mental Hlth Serv VA New York, Brooklyn, NY USA. [AhnAllen, Christopher G.] Inpatient Mental Hlth VA Boston Healthcare Syst, Brockton, MA USA. [AhnAllen, Christopher G.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Wiltsey-Stirman, Shannon; Lester-Williams, Kristin; Resick, Patricia A.] VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Boston, MA USA. [Lester-Williams, Kristin] Midatlantic Mental Illness Res Educ & Clin Ctr, Birmingham, AL USA. [Klunk-Gillis, Julie] VA Boston Healthcare Syst, Mental Hlth Serv, Brockton, MA USA. [Dick, Alexandra M.] Suffolk Univ, Dept Psychol, Boston, MA USA. [Resick, Patricia A.] Duke Univ, Sch Med, Dept Psychiat, Durham, NC 27706 USA. RP Wiltsey-Stirman, S (reprint author), VA Boston Healthcare Syst 116B3, Natl Ctr Posttraumat Stress Disorder, Womens Hlth Sci Div, 150 South Huntington Ave, Boston, MA 02130 USA. EM Shannon.Wiltsey-Stirman@va.gov OI Wiltsey Stirman, Shannon/0000-0001-9917-5078 FU National Institute of Mental Health [T32MH019836, NIMH R00 MH 018100] FX Preparation of this article was funded in part by National Institute of Mental Health Grants T32MH019836 and NIMH R00 MH 018100 NR 42 TC 0 Z9 0 U1 1 U2 9 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 2015 VL 12 IS 3 BP 330 EP 338 DI 10.1037/a0038702 PG 9 WC Psychology, Clinical SC Psychology GA CN8KN UT WOS:000358689300016 PM 25822316 ER PT J AU Gottlieb, DJ AF Gottlieb, Daniel J. TI Does Treatment of Sleep Apnea Prevent Perioperative Complications? Wish We Knew! SO SLEEP LA English DT Editorial Material ID POSITIVE AIRWAY PRESSURE; POSTOPERATIVE OUTCOMES; SURGICAL-PATIENTS; SURGERY; METAANALYSIS; THERAPY; TRIAL C1 [Gottlieb, Daniel J.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Gottlieb, Daniel J.] Harvard Univ, Sch Med, Boston, MA USA. RP Gottlieb, DJ (reprint author), Brigham & Womens Hosp, Div Sleep & Circadian Disorders, 221 Longwood Ave,BLI 225E, Boston, MA 02115 USA. EM djgottlieb@partners.org NR 13 TC 0 Z9 0 U1 0 U2 2 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD AUG 1 PY 2015 VL 38 IS 8 BP 1155 EP 1156 AR PII sp-00360-15 DI 10.5665/sleep.4880 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CO0JV UT WOS:000358838100003 PM 26194573 ER PT J AU Kuna, ST Shuttleworth, D Chi, LQ Schutte-Rodin, S Friedman, E Guo, HY Dhand, S Yang, L Zhu, JS Bellamy, SL Volpp, KG Asch, DA AF Kuna, Samuel T. Shuttleworth, David Chi, Luqi Schutte-Rodin, Sharon Friedman, Eliot Guo, Hengyi Dhand, Sandeep Yang, Lin Zhu, Jingsan Bellamy, Scarlett L. Volpp, Kevin G. Asch, David A. TI Web-Based Access to Positive Airway Pressure Usage with or without an Initial Financial Incentive Improves Treatment Use in Patients with Obstructive Sleep Apnea SO SLEEP LA English DT Article DE adherence; telehealth; internet ID RANDOMIZED CONTROLLED-TRIAL; FORM HEALTH SURVEY; CPAP THERAPY; DAYTIME SLEEPINESS; NASAL CPAP; HEART HEALTH; ADHERENCE; SUPPORT; ADULTS; IMPLEMENTATION AB Study Objectives: We tested whether providing adults with obstructive sleep apnea (OSA) with daily Web-based access to their positive airway pressure (PAP) usage over 3 mo with or without a financial incentive in the first week improves adherence and functional outcomes. Setting: Academic-and community-based sleep centers. Participants: One hundred thirty-eight adults with newly diagnosed OSA starting PAP treatment. Interventions: Participants were randomized to: usual care, usual care with access to PAP usage, or usual care with access to PAP usage and a financial incentive. PAP data were transmitted daily by wireless modem from the participants' PAP unit to a website where hours of usage were displayed. Participants in the financial incentive group could earn up to $30/day in the first week for objective PAP use >= 4 h/day. Measurements and Results: Mean hours of daily PAP use in the two groups with access to PAP usage data did not differ from each other but was significantly greater than that in the usual care group in the first week and over 3 mo (P < 0.0001). Average daily use (mean +/- standard deviation) during the first week of PAP intervention was 4.7 +/- 3.3 h in the usual care group, and 5.9 +/- 2.5 h and 6.3 +/- 2.5 h in the Web access groups with and without financial incentive respectively. Adherence over the 3-mo intervention decreased at a relatively constant rate in all three groups. Functional Outcomes of Sleep Questionnaire change scores at 3 mo improved within each group (P < 0.0001) but change scores of the two groups with Web access to PAP data were not different than those in the control group (P > 0.124). Conclusions: Positive airway pressure adherence is significantly improved by giving patients Web access to information about their use of the treatment. Inclusion of a financial incentive in the first week had no additive effect in improving adherence. C1 [Kuna, Samuel T.; Volpp, Kevin G.; Asch, David A.] Corporal Michael J Crescenz Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Kuna, Samuel T.; Volpp, Kevin G.; Asch, David A.] Corporal Michael J Crescenz Vet Affairs Med Ctr, Dept Med, Philadelphia, PA USA. [Kuna, Samuel T.; Shuttleworth, David; Schutte-Rodin, Sharon; Guo, Hengyi; Volpp, Kevin G.; Asch, David A.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Shuttleworth, David; Yang, Lin; Zhu, Jingsan; Volpp, Kevin G.; Asch, David A.] Ctr Hlth Incent & Behav Econ, Leonard Davis Inst, Philadelphia, PA USA. [Chi, Luqi] Lankenau Med Ctr, Wynnewood, PA USA. [Friedman, Eliot] Paoli Hosp, Paoli, PA USA. [Dhand, Sandeep] Holy Redeemer Hosp, Meadowbrook, PA USA. [Bellamy, Scarlett L.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Volpp, Kevin G.; Asch, David A.] Univ Penn, Wharton Sch, Dept Hlth Care Management, Philadelphia, PA 19104 USA. RP Kuna, ST (reprint author), Philadelphia Vet Affairs Med Ctr, 111P,3900 Woodland Ave, Philadelphia, PA 19104 USA. FU NIH [RC2-AG036592-01, 1P01-1HL094307]; Philips Respironics; Humana; Weight Watchers; CVS FX NIH RC2-AG036592-01; NIH 1P01-1HL094307. P'unk Ave, Inc., a Web-based software company in Philadelphia, PA, created the Way to Health website for the University of Pennsylvania and continued to support the website during the project. Dr. Kuna and Dr. Schutte-Rodin receive grant support from Philips Respironics. Dr. Asch is a Principal at VAL Health (Philadelphia, PA). Dr. Volpp has received research support from Humana, Weight Watchers, and CVS, and has consulted for Val Health. The other authors have indicated no financial conflicts of interest. NR 42 TC 7 Z9 7 U1 0 U2 3 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD AUG 1 PY 2015 VL 38 IS 8 BP 1229 EP 1236 AR PII sp-00550-14 DI 10.5665/sleep.4898 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CO0JV UT WOS:000358838100012 PM 25581921 ER PT J AU Azarbarzin, A Ostrowski, M Younes, M Keenan, BT Pack, AI Staley, B Kuna, ST AF Azarbarzin, Ali Ostrowski, Michele Younes, Magdy Keenan, Brendan T. Pack, Allan I. Staley, Bethany Kuna, Samuel T. TI Arousal Responses during Overnight Polysomnography and their Reproducibility in Healthy Young Adults SO SLEEP LA English DT Article DE arousal; EEG; heart rate; night-to-night ID OBSTRUCTIVE SLEEP-APNEA; NIGHT; HYPERTENSION; VARIABILITY; ASSOCIATION; PERFORMANCE; ACTIVATION; CHILDREN; HUMANS; AGE AB Study Objectives: Arousal intensity and heart rate (HR) response to arousal during polysomnography (PSG) vary considerably between patients with sleep disorders. Our objective was to determine the range of these arousal characteristics in healthy young adults and whether they are consistent on repeated testing. Design: Post hoc analysis of 56 preexisting PSG files recorded from 28 healthy adults on 2 consecutive nights. Setting: Academic medical center and Research and Development Laboratory (YRT Limited, Winnipeg, Manitoba, Canada). Participants: Twenty-eight healthy young adults. Interventions: None. Measurements and Results: Arousals were identified using an automatic system followed by manual editing. The intensity of arousals was scaled (between 0 and 9) using an automatic algorithm based on the change in the electroencephalography (EEG) signals' wavelet characteristics. 4,751 arousals in 28 pairs of PSGs (night 1 and night 2) were scaled. HR responses (Delta HR) to all arousals were determined and averaged at each arousal scale per file. Overall average arousal intensity ranged 3.0-7.1 in different subjects, and average Delta HR ranged 1.9-18.3 beats.min(-1). Heart rate response at a given arousal intensity, expressed as Delta HR at a moderate arousal scale of 5.0 (Delta HR5), ranged 4.1-18.1 beats.min(-1). There was a strong correlation between arousal intensity and Delta HR within each subject. More importantly, there were excellent intraclass correlations (ICC) between night 1 and night 2 results for all three variables (ICC = 0.72 for average intensity, 0.92 for average Delta HR4, and 0.91 for Delta HR5). Conclusions: Average arousal intensity and heart rate response to arousal are highly variable among healthy young adults and stable within individuals. C1 [Azarbarzin, Ali; Ostrowski, Michele; Younes, Magdy] YRT Ltd, Winnipeg, MB, Canada. [Younes, Magdy] Univ Manitoba, Sleep Disorders Ctr, Winnipeg, MB, Canada. [Keenan, Brendan T.; Pack, Allan I.; Staley, Bethany; Kuna, Samuel T.] Univ Penn, Sch Med, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USA. [Pack, Allan I.; Staley, Bethany; Kuna, Samuel T.] Univ Penn, Pereleman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Kuna, Samuel T.] Philadelphia VA Med Ctr, Dept Med, Philadelphia, PA USA. RP Younes, M (reprint author), 1001 Wellington Crescent, Winnipeg, MB R3M 0A7, Canada. EM mkyounes@shaw.ca FU YRT Limited, Winnipeg, Manitoba, Canada; NIH [P50 HL060287, 1P01-1HL094307]; Philips Respironics FX This study was supported by YRT Limited, Winnipeg, Manitoba, Canada; NIH P50 HL060287; NIH 1P01-1HL094307. Dr. Younes is majority owner of YRT Ltd., and receives royalties from Covidien and Philips Respironics. Michele Ostrowski is part owner of YRT. Dr. Azarbarzin is currently employed by YRT. Dr Kuna has received grant support from Philips Respironics and has consulted for Vivus, Astra Zeneca, and Zephyr Sleep Technologies The other authors have indicated no financial conflicts of interest. NR 26 TC 3 Z9 3 U1 1 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD AUG 1 PY 2015 VL 38 IS 8 BP 1313 EP 1321 DI 10.5665/sleep.4916 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CO0JV UT WOS:000358838100021 PM 25581917 ER PT J AU Milian, J Goldfine, AB Zuflacht, JP Parmer, C Beckman, JA AF Milian, Jessica Goldfine, Allison B. Zuflacht, Jonah P. Parmer, Caitlin Beckman, Joshua A. TI Atazanavir improves cardiometabolic measures but not vascular function in patients with long-standing type 1 diabetes mellitus SO ACTA DIABETOLOGICA LA English DT Article DE Type 1 diabetes; Endothelium; Oxidative stress; Bilirubin ID ENDOTHELIUM-DEPENDENT VASODILATION; PLACEBO-CONTROLLED TRIAL; CORONARY-ARTERY-DISEASE; NITRIC-OXIDE SYNTHASE; STABLE ANTIRETROVIRAL THERAPY; ACUTE MYOCARDIAL-INFARCTION; MRC/BHF HEART PROTECTION; TOTAL BILIRUBIN LEVEL; OXIDATIVE STRESS; CARDIOVASCULAR EVENTS AB Vascular disease is the leading cause of morbidity and mortality in type 1 diabetes mellitus (T1DM). We previously demonstrated that patients with T1DM have impaired endothelial function, a forme fruste of atherosclerosis, as a result of increased oxidative stress. Bilirubin has emerged as a potent endogenous antioxidant with higher concentrations associated with lower rates of myocardial infarction and stroke. We tested the hypothesis that increasing endogenous bilirubin using atazanavir would improve cardiometabolic risk factors and vascular function in patients with T1DM to determine whether targeting bilirubin may be a novel therapeutic approach to reduce cardiovascular disease risk in this population. In this single-arm, open-label study, we evaluated blood pressure, lipid profile, and conduit artery function in fifteen subjects (mean age 45 +/- A 9 years) with T1DM following a 4-day treatment with atazanavir. As anticipated, atazanavir significantly increased both serum total bilirubin levels (p < 0.0001) and plasma total antioxidant capacity (p < 0.0001). Reductions in total cholesterol (p = 0.04), LDL cholesterol (p = 0.04), and mean arterial pressure (p = 0.04) were also observed following atazanavir treatment. No changes were seen in either flow-mediated endothelium-dependent (p = 0.92) or nitroglycerine-mediated endothelium-independent (p = 0.68) vasodilation, measured by high-resolution B-mode ultrasonography at baseline and post-treatment. Increasing serum bilirubin levels with atazanavir in subjects with T1DM over 4 days favorably reduces LDL and blood pressure but is not associated with improvements in endothelial function of conduit arteries. C1 [Milian, Jessica; Zuflacht, Jonah P.; Parmer, Caitlin; Beckman, Joshua A.] Brigham & Womens Hosp, Cardiovasc Div, Boston, MA 02115 USA. [Goldfine, Allison B.] Joslin Diabet Ctr, Clin Res, Boston, MA 02215 USA. RP Beckman, JA (reprint author), Brigham & Womens Hosp, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA. EM jbeckman@partners.org OI Beckman, Joshua/0000-0001-8332-8439 FU National Institutes of Health, National Institute of Diabetes, Digestive and Kidney Disease [1R03 DK094510-01]; NIDDK Diabetes Research Center [P30DK036836] FX Dr. Beckman is supported by National Institutes of Health, National Institute of Diabetes, Digestive and Kidney Disease Grant 1R03 DK094510-01. Dr. Goldfine is supported by NIDDK Diabetes Research Center Grant P30DK036836. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. NR 54 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER-VERLAG ITALIA SRL PI MILAN PA VIA DECEMBRIO, 28, MILAN, 20137, ITALY SN 0940-5429 EI 1432-5233 J9 ACTA DIABETOL JI Acta Diabetol. PD AUG PY 2015 VL 52 IS 4 BP 709 EP 715 DI 10.1007/s00592-014-0708-6 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CN0EE UT WOS:000358085800009 PM 25563478 ER PT J AU Stanton, RC AF Stanton, Robert C. TI Metformin Use in Type 2 Diabetes Mellitus With CKD: Is It Time to Liberalize Dosing Recommendations? SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Editorial Material ID LACTIC-ACIDOSIS; RENAL IMPAIRMENT; RISK; COHORT C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Stanton, RC (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM robert.stanton@joslin.harvard.edu NR 16 TC 5 Z9 5 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD AUG PY 2015 VL 66 IS 2 BP 193 EP 195 DI 10.1053/j.ajkd.2015.04.001 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA CN4ED UT WOS:000358382100013 PM 25960301 ER PT J AU Rhee, CM Nguyen, DV Moradi, H Brunelli, SM Dukkipati, R Jing, J Nakata, T Kovesdy, CP Brent, GA Kalantar-Zadeh, K AF Rhee, Connie M. Nguyen, Danh V. Moradi, Hamid Brunelli, Steven M. Dukkipati, Ramanath Jing, Jennie Nakata, Tracy Kovesdy, Csaba P. Brent, Gregory A. Kalantar-Zadeh, Kamyar TI Association of Adiponectin With Body Composition and Mortality in Hemodialysis Patients SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Adiponectin; mortality; hemodialysis; body composition; anthropometry; body fat; body mass index (BMI); lipids; cardiovascular disease (CVD); renal replacement therapy (RRT); end-stage renal disease; MADRAD (Malnutrition, Diet and Racial Disparities in Chronic Kidney Disease) study ID CHRONIC KIDNEY-DISEASE; STAGE RENAL-DISEASE; ALL-CAUSE MORTALITY; CHRONIC HEART-FAILURE; QUALITY-OF-LIFE; DIALYSIS PATIENTS; CARDIOVASCULAR MORTALITY; MYOCARDIAL-INFARCTION; REVERSE EPIDEMIOLOGY; PLASMA-PROTEIN AB Background: In the general population, circulating adiponectin is associated with a favorable cardiovascular risk profile (eg, lower triglycerides and body fat) and decreased mortality. Hemodialysis (HD) patients have comparatively higher adiponectin concentrations, but prior studies examining the adiponectin-mortality association in this population have not accounted for body composition or shown a consistent relationship. Study Design: Prospective cohort study. Settings & Participants: We examined baseline serum adiponectin concentrations in 501 HD patients across 13 dialysis centers from the prospective MADRAD (Malnutrition, Diet, and Racial Disparities in Chronic Kidney Disease) cohort (entry period, October 2011 to February 2013; follow-up through August 2013). Predictor: Serum adiponectin concentration in tertiles (tertiles 1, 2, and 3 defined as <= 16.1, >16.1-<30.1, and >= 30.1-100.0 mu g/mL, respectively). Adjustment variables included case-mix and laboratory test results (age, sex, race, ethnicity, vintage, diabetes, serum albumin, total iron-binding capacity, serum creatinine, white blood cell count, phosphate, hemoglobin, and normalized protein catabolic rate), body composition surrogates (subcutaneous, visceral, and total-body fat and lean body mass), and serum lipid levels (cholesterol, high-density lipoprotein cholesterol, and triglycerides). Outcomes: All-cause mortality using survival (Cox) models incrementally adjusted for case-mix and laboratory test results. Results: Among 501 HD patients, 50 deaths were observed during 631.1 person-years of follow-up. In case-mix- and laboratory-adjusted Cox analyses, the highest adiponectin tertile was associated with increased mortality versus the lowest tertile (HR, 3.35; 95% CI, 1.50-7.47). These associations were robust in analyses that additionally accounted for body composition (HR, 3.18; 95% CI, 1.61-8.24) and lipid levels (HR, 3.64; 95% CI, 1.34-7.58). Limitations: Residual confounding cannot be excluded. Conclusions: Higher adiponectin level is associated with a 3-fold higher death risk in HD patients independent of body composition and lipid levels. Future studies are needed to elucidate underlying mechanisms and determine therapeutic targets associated with improved outcomes in HD patients. (C) 2015 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved. C1 [Rhee, Connie M.; Moradi, Hamid; Jing, Jennie; Nakata, Tracy; Kalantar-Zadeh, Kamyar] Univ Calif Irvine, Harold Simmons Ctr Kidney Dis Res & Epidemiol, Div Nephrol & Hypertens, Orange, CA 92868 USA. [Nguyen, Danh V.] Univ Calif Irvine, Div Gen Internal Med, Orange, CA 92868 USA. [Brunelli, Steven M.] DaVita Healthcare Partners Inc, Minneapolis, MN USA. [Dukkipati, Ramanath] Harbor UCLA Med Ctr, Div Nephrol, Torrance, CA 90509 USA. [Kovesdy, Csaba P.] Univ Tennessee, Hlth Sci Ctr, Knoxville, TN 37996 USA. [Kovesdy, Csaba P.] Memphis VA Med Ctr, Div Nephrol, Memphis, TN USA. [Brent, Gregory A.] VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. RP Rhee, CM (reprint author), Univ Calif Irvine, Harold Simmons Ctr Kidney Dis Res & Epidemiol, Div Nephrol & Hypertens, Med Ctr, 101 City Dr S, Orange, CA 92868 USA. EM crhee1@uci.edu OI Kalantar-Zadeh, Kamyar/0000-0002-8666-0725 FU National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases [K23-DK102903, K24-DK091419, R01-DK078106]; National Center for Advancing Translational Sciences grant [UL1 TR000153] FX Support: This study is supported by research grants from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases, including K23-DK102903 (Dr Rhee) and K24-DK091419 and R01-DK078106 (both Dr Kalantar-Zadeh), and philanthropic grants from Mr Harold Simmons and Mr Louis Chang. Dr Nguyen is supported by a National Center for Advancing Translational Sciences grant (UL1 TR000153). The study sponsors did not have a role in the study design; collection, analysis, or interpretation of data; writing the report; or the decision to submit the report for publication. NR 53 TC 10 Z9 10 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD AUG PY 2015 VL 66 IS 2 BP 313 EP 321 DI 10.1053/j.ajkd.2015.02.325 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA CN4ED UT WOS:000358382100027 PM 25824125 ER PT J AU Trbovich, M Yang, HQ AF Trbovich, Michelle Yang, Huiqing TI Capsaicin 8% Patch for Central and Peripheral Neuropathic Pain of Persons with Incomplete Spinal Cord Injury Two Case Reports SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Capsaicin; Neuropathic Pain; Spinal Cord Injury; Transient Receptor Potential Vanilloid Receptor ID QUALITY-OF-LIFE; BASIC DATA SET; MANAGEMENT; NOCICEPTORS; MECHANISMS AB Neuropathic pain after spinal cord injury is common and often refractory to standard treatments. The capsaicin 8% patch is a Food and Drug Administration-approved treatment of neuropathic pain in postherpetic neuralgia and has demonstrated significant efficacy in human immunodeficiency virus-autonomic neuropathy. The patch defunctionalizes transient receptor potential vanilloid 1 receptors, impairing cutaneous nociceptors for a prolonged period (i.e., 8-12 wks) with no systemic side effects. A retrospective review was conducted on the effects of the patch in two patients with spinal cord injury and neuropathic pain refractory to standard treatments. Two weeks after application, both patients reported complete pain relief. Average onset of relief of 4 days and average duration of relief of 197 days, requiring only one to four applications per year, paralleled findings reported in postherpetic neuralgia and human immunodeficiency virus-autonomic neuropathy trials. Upregulation of capsaicin-sensitive transient receptor potential vanilloid 1 receptors after spinal cord injury has been reported. The capsaicin 8% patch is a promising therapeutic agent for neuropathic pain in spinal cord injury. C1 [Trbovich, Michelle; Yang, Huiqing] Univ Texas Hlth Sci Ctr San Antonio, Dept Rehabil Med, San Antonio, TX 78229 USA. [Trbovich, Michelle] Audie L Murphy Mem Vet Adm Med Ctr, Spinal Cord Injury Serv, San Antonio, TX USA. RP Trbovich, M (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Rehabil Med, Mail Code 7798,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 35 TC 1 Z9 1 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0894-9115 EI 1537-7385 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD AUG PY 2015 VL 94 IS 8 BP E66 EP E72 DI 10.1097/PHM.0000000000000301 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA CN0RY UT WOS:000358122300001 PM 26035723 ER PT J AU Ladha, KS Nanji, KC Pierce, E Poon, KT Hyder, JA AF Ladha, Karim S. Nanji, Karen C. Pierce, Eric Poon, K. Trudy Hyder, Joseph A. TI The Impact of a Shortage of Pharmacy-Prepared Ephedrine Syringes on Intraoperative Medication Use SO ANESTHESIA AND ANALGESIA LA English DT Article ID SIGNIFICANT WASTE; APGAR SCORE; ANESTHESIA; DRUGS; STRATEGIES; MANAGEMENT; RISK AB BACKGROUND: Anesthesia-related medication shortages have become increasingly common in the United States. We tested whether a local shortage of pharmacy-prepared ephedrine syringes, replaced by provider-prepared ephedrine, was associated with provider-level changes in ephedrine and phenylephrine use and patient-level changes in intraoperative hemodynamics. METHODS: Consecutive patients undergoing general and orthopedic surgery at a tertiary care center were included 1 month before and 1 month after the start of the pharmacy-prepared ephedrine syringe shortage. Lowest mean arterial blood pressure and slowest heart rate were obtained as measures of hemodynamics. Adjusted associations were tested using mixed-effects regression with repeated measures. RESULTS: Three hundred four patients before the shortage and 298 patients after the shortage began were included. The administration of at least 1 bolus of ephedrine was significantly more common before versus during the shortage (148/304 [48.7]% vs 117/298 [39.3]%; P = 0.0199). After adjusting for age, sex, ASA physical status, surgery type, anesthesia provider, and operative duration, patients were significantly less likely to receive ephedrine during the shortage (relative risk [RR] = 0.78 [95% confidence interval {CI}, 0.61-0.96]; P = 0.0198) and more likely to receive a phenylephrine bolus (RR = 1.27 [95% CI, 1.02-1.51]; P = 0.0357). Patient hemodynamics assessed by slowest heart rate or lowest mean arterial blood pressure did not differ significantly during the shortage. CONCLUSIONS: There was an alteration in medication administration patterns during a shortage of pharmacy-prepared syringes. Changes in ephedrine and phenylephrine use were noted; however, patient hemodynamics remained comparable. Provider use patterns were sensitive even to a relative and not absolute medication shortage as observed in this study. C1 [Ladha, Karim S.; Nanji, Karen C.; Pierce, Eric; Poon, K. Trudy] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. [Hyder, Joseph A.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Ladha, Karim S.; Nanji, Karen C.; Pierce, Eric] Harvard Univ, Sch Med, Boston, MA USA. RP Ladha, KS (reprint author), Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM kladha@partners.org RI Ladha, Karim/K-7170-2015 OI Ladha, Karim/0000-0001-7303-2458 NR 13 TC 1 Z9 1 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD AUG PY 2015 VL 121 IS 2 BP 404 EP 409 DI 10.1213/ANE.0000000000000809 PG 6 WC Anesthesiology SC Anesthesiology GA CN4FP UT WOS:000358386300003 PM 26076388 ER PT J AU Xu, XG Liu, TY Su, L Du, XN Riblett, M Ji, W Gu, DY Carothers, CD Shephard, MS Brown, FB Kalra, MK Liu, B AF Xu, X. George Liu, Tianyu Su, Lin Du, Xining Riblett, Matthew Ji, Wei Gu, Deyang Carothers, Christopher D. Shephard, Mark S. Brown, Forrest B. Kalra, Mannudeep K. Liu, Bob TI ARCHER, a new Monte Carlo software tool for emerging heterogeneous computing environments SO ANNALS OF NUCLEAR ENERGY LA English DT Article; Proceedings Paper CT Joint International Conference on Supercomputing in Nuclear Application (SNA) and Monte Carlo (MC) CY OCT 27-31, 2013 CL Paris, FRANCE DE Monte Carlo; Parallel computing; GPU; CUDA; Intel Xeon Phi coprocessor; Radiation dose ID DOSE CALCULATIONS; GPU IMPLEMENTATION; MULTIDETECTOR CT; SIMULATIONS; VALIDATION; TRANSPORT; ALGORITHM; ELECTRONS; PHOTON; GEANT4 AB The Monte Carlo radiation transport community faces a number of challenges associated with peta- and exa-scale computing systems that rely increasingly on heterogeneous architectures involving hardware accelerators such as GPUs and Xeon Phi coprocessors. Existing Monte Carlo codes and methods must be strategically upgraded to meet emerging hardware and software needs. In this paper, we describe the development of a software, called ARCHER (Accelerated Radiation-transport Computations in Heterogeneous EnviRonments), which is designed as a versatile testbed for future Monte Carlo codes. Preliminary results from five projects in nuclear engineering and medical physics are presented. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Xu, X. George; Liu, Tianyu; Su, Lin; Du, Xining; Riblett, Matthew; Ji, Wei; Gu, Deyang; Carothers, Christopher D.; Shephard, Mark S.] Rensselaer Polytech Inst, Troy, NY 12180 USA. [Brown, Forrest B.] Los Alamos Natl Lab, Los Alamos, NM USA. [Kalra, Mannudeep K.; Liu, Bob] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Xu, XG (reprint author), Rensselaer Polytech Inst, Troy, NY 12180 USA. EM xug2@rpi.edu OI Riblett, Matthew/0000-0003-1049-1774 FU U.S. National Institute of Biomedical Imaging and Bioengineering [R01EB0 15478] FX Research is supported in part by a grant from the U.S. National Institute of Biomedical Imaging and Bioengineering (R01EB0 15478). NR 28 TC 2 Z9 2 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4549 J9 ANN NUCL ENERGY JI Ann. Nucl. Energy PD AUG PY 2015 VL 82 SI SI BP 2 EP 9 DI 10.1016/j.anucene.2014.08.062 PG 8 WC Nuclear Science & Technology SC Nuclear Science & Technology GA CN0IJ UT WOS:000358097000002 ER PT J AU Axelrod, DA Vagefi, PA Roberts, JP AF Axelrod, David A. Vagefi, Parsia A. Roberts, John P. TI The Evolution of Organ Allocation for Liver Transplantation Tackling Geographic Disparity Through Broader Sharing SO ANNALS OF SURGERY LA English DT Article ID SURVIVAL BENEFIT; OUTCOMES; RATES; MELD C1 [Axelrod, David A.] Dartmouth Hitchcock Med Ctr, Dept Surg, Lebanon, NH 03756 USA. [Axelrod, David A.; Vagefi, Parsia A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Roberts, John P.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. RP Axelrod, DA (reprint author), Dartmouth Hitchcock Med Ctr, Solid Organ Transplantat, Lebanon, NH 03756 USA. EM david.axelrod@hitchcock.org NR 18 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD AUG PY 2015 VL 262 IS 2 BP 224 EP 227 DI 10.1097/SLA.0000000000001340 PG 4 WC Surgery SC Surgery GA CM8KG UT WOS:000357948600005 PM 26164429 ER PT J AU Massarweh, NN Haynes, AB Chiang, YJ Chang, GJ You, YN Feig, BW Cormier, JN AF Massarweh, Nader N. Haynes, Alex B. Chiang, Yi-Ju Chang, George J. You, Y. Nancy Feig, Barry W. Cormier, Janice N. TI Adequacy of the National Quality Forum's Colon Cancer Adjuvant Chemotherapy Quality Metric Is 4 Months Soon Enough? SO ANNALS OF SURGERY LA English DT Article DE adjuvant chemotherapy; colon cancer; National Quality Forum; quality metric; quality of care ID COLORECTAL-CANCER; DATA-BASE; UNITED-STATES; SURVIVAL-ANALYSIS; STAGE-II; FLUOROURACIL; SURGERY; LEUCOVORIN; LEVAMISOLE; CARCINOMA AB Objective: To ascertain whether the National Quality Forum-endorsed time interval for adjuvant chemotherapy (AC) initiation optimizes patient outcome. Background: Delayed AC initiation for stage III colon cancer is associated with worse survival and the focus of a National Quality Forum quality metric (<4 months among patients aged <80 years). Methods: Observational cohort study of patients with stage III colon cancer younger than 80 years within the National Cancer Data Base (2003-2010). The primary outcome was 5-year overall survival evaluated using multivariate Cox proportional hazards regression. Aggregate survival estimates for historical surgery-only controls from pooled National Surgical Adjuvant Breast and Bowel Project trial data were also used. Results: Among 51,331 patients (60.8 11.6 years, 50.2% males, and 77.3% white), 76.3% received standard AC (2 months) and 21.6% delayed (>2 and <4 months) AC. Earlier AC was associated with better 5-year overall survival [standard AC, 69.8%; delayed AC, 62.0%; late AC (4-6 months), 51.4%; log-rank, P < 0.001]. The survival rate after late AC was similar to surgery alone (51.1%; Wilcoxon rank sum, P = 0.10). Compared with late AC, standard AC (hazard ratio, 0.62; 95% confidence interval, 0.54-0.72) and delayed AC (hazard ratio, 0.77; 95% confidence interval, 0.66-0.89) significantly decreased risk of death. Risk of death was also lower for standard AC compared to delayed AC (hazard ratio, 0.81; 95% confidence interval, 0.77-0.86). Conclusions: One in 5 patients with stage III colon cancer initiates AC within the National Quality Forum-endorsed interval, but does not derive the full benefit. These data support strengthening current quality improvement initiatives and colon cancer treatment guidelines to encourage AC initiation within 2 months of resection when possible, but not beyond 4 months. C1 [Massarweh, Nader N.; Chiang, Yi-Ju; Chang, George J.; You, Y. Nancy; Feig, Barry W.; Cormier, Janice N.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77230 USA. [Haynes, Alex B.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Massarweh, NN (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Unit 1484, Box 301402, Houston, TX 77230 USA. EM jcormier@mdanderson.org FU National Institutes of Health/National Cancer Institute [CA16672] FX Supported by National Institutes of Health/National Cancer Institute grant CA16672 (The University of Texas MD Anderson Cancer Center Support Grant). NR 34 TC 3 Z9 3 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD AUG PY 2015 VL 262 IS 2 BP 312 EP 320 DI 10.1097/SLA.0000000000000859 PG 9 WC Surgery SC Surgery GA CM8KG UT WOS:000357948600019 PM 25185467 ER PT J AU Fong, ZV Correa-Gallego, C Ferrone, CR Veillette, GR Warshaw, AL Lillemoe, KD Fernandez-del Castillo, C AF Fong, Zhi Ven Correa-Gallego, Camilo Ferrone, Cristina R. Veillette, Gregory R. Warshaw, Andrew L. Lillemoe, Keith D. Fernandez-del Castillo, Carlos TI Early Drain Removal-The Middle Ground Between the Drain Versus No Drain Debate in Patients Undergoing Pancreaticoduodenectomy A Prospective Validation Study SO ANNALS OF SURGERY LA English DT Article DE drain amylase; early drain removal; intraperitoneal drain; pancreatic fistula; pancreaticoduodenectomy ID MULTIINSTITUTIONAL EXTERNAL VALIDATION; UNDERSTANDING HOSPITAL READMISSIONS; POSTOPERATIVE PANCREATIC FISTULA; SINGLE-INSTITUTION EXPERIENCE; PROSPECTIVE-RANDOMIZED-TRIAL; INTERNATIONAL STUDY-GROUP; INTRAPERITONEAL DRAINAGE; SURGICAL COMPLICATIONS; ACADEMIC INSTITUTION; CRITICAL PATHWAY AB Objective: To perform an unbiased assessment of first postoperative day (POD 1) drain amylase level and pancreatic fistula (PF) after pancreaticoduodenectomy (PD). Background: Recent evidence demonstrated that drain abandonment in PD is unsafe. Early drain amylase levels have been proposed as predictors of PF after PD, allowing for selection of patients for early drain removal. Methods: Daily drain amylase levels were correlated with the development of PF in 2 independent cohorts of patients undergoing PD: training cohort (n = 126; year 2008) and validation cohort (n = 369; years 2009-2012). Results: POD 1 drain amylase level had the highest predictive ability (concordance index: 0.911) for PF in the training cohort. An amylase level of 612 U/L or higher showed the best accuracy (86%), sensitivity (93%), and specificity (79%). Thus, a cutoff value of 600 U/L was utilized. In the validation cohort, 229 (62.1%) patients had a POD 1 drain amylase level of lower than 600 U/L, and PF developed in only 2 (0.9%) cases; whereas in patients with POD 1 drain amylase level of 600 U/L or higher (n = 140) the PF rate was 31.4% (odds ratio [OR] = 52, P < 0.0001). On multivariate analysis, POD 1 drain amylase level of lower than 600 U/L (OR = 0.0192, P < 0.0001) was a stronger predictor of the absence of PF than pancreatic gland texture (OR = 0.193, P = 0.002) and duct diameter (OR = 0.861, P = 0.835). Conclusions: After PD, the risk of PF is less than 1% if POD 1 drain amylase level is lower than 600 U/L. We propose that in this group, which comprise more than 60% of patients, drains should be removed on POD 1. C1 [Fong, Zhi Ven; Correa-Gallego, Camilo; Ferrone, Cristina R.; Veillette, Gregory R.; Warshaw, Andrew L.; Lillemoe, Keith D.; Fernandez-del Castillo, Carlos] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. RP Fernandez-del Castillo, C (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St, Boston, MA 02114 USA. EM cfernandez@partners.org NR 43 TC 7 Z9 7 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD AUG PY 2015 VL 262 IS 2 BP 378 EP 383 DI 10.1097/SLA.0000000000001038 PG 6 WC Surgery SC Surgery GA CM8KG UT WOS:000357948600027 ER PT J AU Qamar, A Khetarpal, SA Khera, AV Qasim, A Rader, DJ Reilly, MP AF Qamar, Arman Khetarpal, Sumeet A. Khera, Amit V. Qasim, Atif Rader, Daniel J. Reilly, Muredach P. TI Plasma Apolipoprotein C-III Levels, Triglycerides, and Coronary Artery Calcification in Type 2 Diabetics SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE apolipoproteins; atherosclerosis; risk factors; type 2 diabetes mellitus ID LOW-DENSITY-LIPOPROTEIN; APOC-III; HEART-DISEASE; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; POTENTIAL MECHANISM; METABOLIC SYNDROME; RICH LIPOPROTEINS; RANDOMIZED-TRIALS; LDL CHOLESTEROL AB Objective Triglyceride-rich lipoproteins have emerged as causal risk factors for developing coronary heart disease independent of low-density lipoprotein cholesterol levels. Apolipoprotein C-III (ApoC-III) modulates triglyceride-rich lipoprotein metabolism through inhibition of lipoprotein lipase and hepatic uptake of triglyceride-rich lipoproteins. Mutations causing loss-of-function of ApoC-III lower triglycerides and reduce coronary heart disease risk, suggestive of a causal role for ApoC-III. Little data exist about the relationship of ApoC-III, triglycerides, and atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Here, we examined the relationships between plasma ApoC-III, triglycerides, and coronary artery calcification in patients with T2DM. Approach and Results Plasma ApoC-III levels were measured in a cross-sectional study of 1422 subjects with T2DM but without clinically manifest coronary heart disease. ApoC-III levels were positively associated with total cholesterol (Spearman r=0.36), triglycerides (r=0.59), low-density lipoprotein cholesterol (r=0.16), fasting glucose (r=0.16), and glycosylated hemoglobin (r=0.12; P<0.0001 for all). In age, sex, and race-adjusted analysis, ApoC-III levels were positively associated with coronary artery calcification (Tobit regression ratio, 1.78; 95% confidence interval, 1.27-2.50 per SD increase in ApoC-III; P<0.001). As expected for an intermediate mediator, these findings were attenuated when adjusted for both triglycerides (Tobit regression ratio, 1.43; 95% confidence interval, 0.94-2.18; P=0.086) and separately for very low-density lipoprotein cholesterol (Tobit regression ratio, 1.14; 95% confidence interval, 0.75-1.71; P=0.53). Conclusions In persons with T2DM, increased plasma ApoC-III is associated with higher triglycerides, less favorable cardiometabolic phenotypes, and higher coronary artery calcification, a measure of subclinical atherosclerosis. Therapeutic inhibition of ApoC-III may thus be a novel strategy for reducing plasma triglyceride-rich lipoproteins and cardiovascular risk in T2DM. C1 [Qamar, Arman; Khetarpal, Sumeet A.; Rader, Daniel J.; Reilly, Muredach P.] Univ Penn, Dept Med, Cardiovasc Inst, Perelman Sch Med, Philadelphia, PA 19104 USA. [Khera, Amit V.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Qamar, Arman] Univ Calif San Francisco, Dept Med, Div Cardiol, San Francisco, CA 94143 USA. RP Reilly, MP (reprint author), 11-136 SCTR,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM rader@mail.med.upenn.edu; muredach@mail.med.upenn.edu FU University of Pennsylvania Medical Scientist Training Program; National Institutes of Health [F30 HL124967]; [K24 HL107643]; [R37 HL055323]; [R01 HL113147]; [R01 HL111694]; [R01 DK090505]; [U01 HL108636] FX This work and related research was supported by K24 HL107643 to M.P. Reilly and R37 HL055323 to D.J. Rader. M.P. Reilly is also supported by R01 HL113147, R01 HL111694, R01 DK090505, and U01 HL108636. S.A. Khetarpal is supported in by the University of Pennsylvania Medical Scientist Training Program and by the F30 HL124967 fellowship from the National Institutes of Health. NR 49 TC 15 Z9 15 U1 0 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 2015 VL 35 IS 8 BP 1880 EP 1888 DI 10.1161/ATVBAHA.115.305415 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CN2ZC UT WOS:000358291100018 PM 26069232 ER PT J AU Ostadhadi, S Haj-Mirzaian, A Azimi, E Mansouri, P Dehpour, AR AF Ostadhadi, S. Haj-Mirzaian, A. Azimi, E. Mansouri, P. Dehpour, A. R. TI Involvement of nitric oxide in serotonin-induced scratching in mice SO CLINICAL AND EXPERIMENTAL DERMATOLOGY LA English DT Article ID UREMIC PRURITUS; ONDANSETRON; ITCH; 5-HYDROXYTRYPTAMINE; HISTAMINE; RESPONSES; PSORIASIS; SYNTHASE; PATHWAY AB Background. Serotonin is a pruritogenic substance in humans and animals, but the mechanisms of action through which serotonin induces itch response are not yet understood. Aim. To examine the possible role of nitric oxide (NO) in the profile of scratching behaviour due to intradermal injection of serotonin in mice. Methods. Intradermal injection of serotonin (14.1-235nmol per site) into the nape of the neck was used to elicit itch in mice. Scratching behaviour was evaluated by counting the number of bouts during 60min after injection. To determine the possible involvement of the nitrergic system in serotonin-induced scratching, L-NG-nitroarginine methyl ester [L-NAME; a nonselective nitric oxide synthase (NOS) inhibitor], aminoguanidine [a selective inducible (i)NOS inhibitor] and L-arginine (an NO precursor) were administered intraperitoneally to control and serotonin-injected animals. Results. Intradermal serotonin caused scratching in mice with a bell-shaped dose-response correlation, and the peak effective dose was 141nmol per site. The majority of scratching bouts in animals occurred 5-10min after injection. Ineffective doses of L-NAME (3mg/kg IP) and aminoguanidine (100mg/kg IP) decreased the scratching induced by intradermal serotonin injection in animals (P<0.001 and P<0.001), while an subeffective dose of L-arginine (100mg/kg IP) augmented the scratching effect of serotonin (P<0.001). Conclusions. We show for the first time that the scratching induced by intradermal serotonin is mediated by NOS, especially iNOS, activation. We conclude that NO may play a role in mediating itch responses. NO and NOS could be new targets for antipruritic agents. C1 [Ostadhadi, S.; Haj-Mirzaian, A.; Dehpour, A. R.] Univ Tehran Med Sci, Expt Med Res Ctr, Tehran, Iran. [Mansouri, P.] Univ Tehran Med Sci, Skin & Stem cell Res Ctr, Tehran, Iran. [Ostadhadi, S.; Haj-Mirzaian, A.; Dehpour, A. R.] Univ Tehran Med Sci, Sch Med, Dept Pharmacol, Tehran, Iran. [Azimi, E.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. RP Dehpour, AR (reprint author), Univ Tehran Med Sci, Sch Med, Dept Pharmacol, POB 13145-784, Tehran, Iran. EM dehpoura@sina.tums.ac.ir OI dehpour, ahmad reza/0000-0002-8001-5565 NR 25 TC 5 Z9 5 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0307-6938 EI 1365-2230 J9 CLIN EXP DERMATOL JI Clin. Exp. Dermatol. PD AUG PY 2015 VL 40 IS 6 BP 647 EP 652 DI 10.1111/ced.12605 PG 6 WC Dermatology SC Dermatology GA CN1RP UT WOS:000358198100013 PM 25703534 ER PT J AU Stewart, MO Karlin, BE Murphy, JL Raffa, SD Miller, SA McKellar, J Kerns, RD AF Stewart, Michael O. Karlin, Bradley E. Murphy, Jennifer L. Raffa, Susan D. Miller, Sarah A. McKellar, John Kerns, Robert D. TI National Dissemination of Cognitive-Behavioral Therapy for Chronic Pain in Veterans Therapist and Patient-level Outcomes SO CLINICAL JOURNAL OF PAIN LA English DT Article DE cognitive-behavioral therapy; chronic pain; dissemination; training; Veterans; US Department of Veterans Affairs ID LOW-BACK-PAIN; HEALTH-CARE-SYSTEM; QUALITY-OF-LIFE; WORKING ALLIANCE INVENTORY; BECK DEPRESSION INVENTORY; PSYCHOMETRIC PROPERTIES; CONTROLLED-TRIAL; AFFAIRS; IMPLEMENTATION; METAANALYSIS AB Objective: This paper assesses the effects of training in and implementation of Cognitive-Behavioral Therapy for Chronic Pain (CBT-CP) in the US Department of Veterans Affairs (VA) health care system on therapists' CBT-CP competencies and patients' pain-related outcomes. Methods: A total of 71 therapists participated in the VA CBT-CP Training Program. Patients included 148 Veterans treated by therapist training participants. Therapists completed a 3-day workshop followed by 6 months of weekly consultation. Therapy session tapes were rated by expert training consultants using a standardized competency rating form. Patient outcomes were assessed with measures of patient-reported pain intensity, pain-related cognitions, overall distress, depression, pain interference, and quality of life. The therapeutic alliance was also assessed. Results: Among the 71 therapists who participated in the training program, 60 (85%) completed all training requirements, including competency-based performance criteria. Of the 148 Veteran patients treated, 117 (79%) completed all CBT-CP protocol sessions. Intent-to-treat analyses indicated significant improvements in pain catastrophizing, interference, quality of life, and other domains, as well as on the therapeutic alliance. Discussion: Training in and implementation of CBT-CP in the VA health care system were associated with significant increases in therapist competencies to deliver CBT-CP and improvements in several domains for Veteran patients. Results support the feasibility and effectiveness of broad dissemination of CBT-CP in routine, nonpain specialty settings. C1 [Stewart, Michael O.; Karlin, Bradley E.; Raffa, Susan D.; Miller, Sarah A.] US Dept Vet Affairs, Mental Hlth Serv, Cent Off, Washington, DC USA. [Karlin, Bradley E.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Murphy, Jennifer L.] James A Haley Vet Hosp, Tampa, FL USA. [Murphy, Jennifer L.] Univ S Florida, Tampa, FL USA. [Raffa, Susan D.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [McKellar, John] Bay Area Pain & Wellness Ctr, Los Gatos, CA USA. [Kerns, Robert D.] VA Connecticut Healthcare Syst, PRIME Ctr, Newington, CT USA. [Kerns, Robert D.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Kerns, Robert D.] Yale Univ, Dept Neurol, New Haven, CT USA. RP Stewart, MO (reprint author), VA Tennessee Valley Healthcare Syst, 3400 Lebanon Pike Bldg 147, Murfreesboro, TN 37129 USA. EM michael.stewart@va.gov FU Mental Health Services, US Department of Veterans Affairs Central Office, Washington, DC FX Supported by Mental Health Services, US Department of Veterans Affairs Central Office, Washington, DC. The authors declare no conflict of interest. NR 43 TC 1 Z9 1 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0749-8047 EI 1536-5409 J9 CLIN J PAIN JI Clin. J. Pain PD AUG PY 2015 VL 31 IS 8 BP 722 EP 729 DI 10.1097/AJP.0000000000000151 PG 8 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA CN1VH UT WOS:000358207900007 PM 25171637 ER EF