FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Jacobs, HIL Leritz, EC Williams, VJ Van Boxtel, MPJ van der Elst, W Jolles, J Verhey, FRJ McGlinchey, RE Milberg, WP Salat, DH AF Jacobs, Heidi I. L. Leritz, Elizabeth C. Williams, Victoria J. Van Boxtel, Martin P. J. van der Elst, Wim Jolles, Jelle Verhey, Frans R. J. McGlinchey, Regina E. Milberg, William P. Salat, David H. TI Association between white matter microstructure, executive functions, and processing speed in older adults: The impact of vascular health SO HUMAN BRAIN MAPPING LA English DT Review DE blood pressure; hypertension; white matter signal abnormalities; diffusion tensor imaging; aging; executive function ID MILD COGNITIVE IMPAIRMENT; SURFACE-BASED ANALYSIS; DIFFUSION TENSOR; BLOOD-PRESSURE; MULTIPLE-SCLEROSIS; ALZHEIMERS-DISEASE; CORTICAL DISCONNECTION; RISK-FACTORS; FOLLOW-UP; NEUROPSYCHOLOGICAL IMPAIRMENT AB Cerebral white matter damage is not only a commonly reported consequence of healthy aging, but is also associated with cognitive decline and dementia. The aetiology of this damage is unclear; however, individuals with hypertension have a greater burden of white matter signal abnormalities (WMSA) on MR imaging than those without hypertension. It is therefore possible that elevated blood pressure (BP) impacts white matter tissue structure which in turn has a negative impact on cognition. However, little information exists about whether vascular health indexed by BP mediates the relationship between cognition and white matter tissue structure. We used diffusion tensor imaging to examine the impact of vascular health on regional associations between white matter integrity and cognition in healthy older adults spanning the normotensive to moderatesevere hypertensive BP range (4387 years; N = 128). We examined how white matter structure was associated with performance on tests of two cognitive domains, executive functioning (EF) and processing speed (PS), and how patterns of regional associations were modified by BP and WMSA. Multiple linear regression and structural equation models demonstrated associations between tissue structure, EF and PS in frontal, temporal, parietal, and occipital white matter regions. Radial diffusivity was more prominently associated with performance than axial diffusivity. BP only minimally influenced the relationship between white matter integrity, EF and PS. However, WMSA volume had a major impact on neurocognitive associations. This suggests that, although BP and WMSA are causally related, these differential metrics of vascular health may act via independent pathways to influence brain structure, EF and PS. Hum Brain Mapp, 2013. (c) 2011 Wiley Periodicals, Inc. C1 [Jacobs, Heidi I. L.; Van Boxtel, Martin P. J.; van der Elst, Wim; Jolles, Jelle; Verhey, Frans R. J.] Maastricht Univ, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Alzheimer Ctr Limburg, NL-6200 MD Maastricht, Netherlands. [Jacobs, Heidi I. L.; Van Boxtel, Martin P. J.; van der Elst, Wim; Jolles, Jelle; Verhey, Frans R. J.] Maastricht Univ, European Grad Sch Neurosci EURON, NL-6200 MD Maastricht, Netherlands. [Leritz, Elizabeth C.; Williams, Victoria J.; Salat, David H.] Harvard Univ, Harvard Med Sch, Boston, MA USA. [Leritz, Elizabeth C.; Williams, Victoria J.; McGlinchey, Regina E.; Milberg, William P.; Salat, David H.] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02115 USA. [Leritz, Elizabeth C.; Williams, Victoria J.; McGlinchey, Regina E.; Milberg, William P.; Salat, David H.] VA Healthcare Syst, Neuroimaging Res Vet Ctr, Boston, MA USA. [Leritz, Elizabeth C.; Williams, Victoria J.; McGlinchey, Regina E.; Milberg, William P.; Salat, David H.] VA Healthcare Syst, GRECC, Boston, MA USA. [Jolles, Jelle] Vrije Univ Amsterdam, Fac Psychol & Educ, AZIRE Res Inst, Amsterdam, Netherlands. RP Jacobs, HIL (reprint author), Maastricht Univ, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Alzheimer Ctr Limburg, POB 616, NL-6200 MD Maastricht, Netherlands. EM h.jacobs@maastrichtuniversity.nl RI Jacobs, Heidi/E-9550-2011; McGlinchey, Regina/R-1971-2016 OI Jacobs, Heidi/0000-0001-7620-3822; FU FP6 EU programme Marie Curie Actions [MEST-CT-2005-020589]; National Institute of Health [K23NS062148, K23NS06214802S1, K01AG24898, R01NR010827]; Medical Research Service VA Merit Review Award FX Contract grant sponsor: FP6 EU programme Marie Curie Actions; Contract grant number: MEST-CT-2005-020589; Contract grant sponsor: National Institute of Health; Contract grant numbers: K23NS062148, K23NS06214802S1, K01AG24898, R01NR010827; Contract grant sponsor: Medical Research Service VA Merit Review Award. NR 124 TC 37 Z9 38 U1 5 U2 35 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD JAN PY 2013 VL 34 IS 1 BP 77 EP 95 DI 10.1002/hbm.21412 PG 19 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 057BZ UT WOS:000312538200006 PM 21954054 ER PT J AU Hung, T Piris, A Lobo, A Mihm, MC Sober, AJ Tsao, H Tanabe, KK Duncan, LM AF Hung, Tawny Piris, Adriano Lobo, Alice Mihm, Martin C., Jr. Sober, Arthur J. Tsao, Hensin Tanabe, Kenneth K. Duncan, Lyn M. TI Sentinel lymph node metastasis is not predictive of poor outcome in patients with problematic spitzoid melanocytic tumors SO HUMAN PATHOLOGY LA English DT Article DE Atypical Spitz tumor; Melanoma; Spitz nevus; Sentinel lymph node ID IN-SITU HYBRIDIZATION; ATYPICAL VARIANTS; MALIGNANT-MELANOMA; RISK-ASSESSMENT; SPINDLE CELL; BIOPSY; NEVI; LESIONS; INVOLVEMENT; NEOPLASMS AB The diagnosis and clinical management of spitzoid melanocytic tumors with atypical features remain problematic and controversial. In the past decade, sentinel lymph node mapping has been advocated as a diagnostic test in this setting to discriminate melanoma from benign tumors. Recent studies, however, consistently show that despite the presence of lymph node metastases these patients almost always fare well. We investigated the outcome of patients with atypical Spitz tumors and spitzoid melanoma who received sentinel lymph node mapping to clarify current recommendations in managing patients with these diagnostically challenging tumors. A search of the electronic files of the Massachusetts General Hospital Pathology Service identified 41 patients treated with sentinel lymph node biopsy for atypical Spitz tumor or spitzoid melanoma from 1998 to 2008. These patients included 23 patients with atypical Spitz tumors and 17 patients with spitzoid melanoma. Sentinel lymph nodes were positive in 26% of patients with atypical spitz tumors (6/23) and 35% with spitzoid melanomas (6/17). One patient with spitzoid melanoma developed in-transit metastasis; 0 of 40 patients developed metastases beyond the regional lymph node basin with a mean follow-up of 57 months. Sentinel lymph node biopsy may not be a reliable prognostic discriminatory test in patients with atypical Spitz tumors. Patients with spitzoid melanomas and positive sentinel lymph nodes have a more indolent course than those with bona fide conventional melanoma and positive sentinel nodes. (C) 2013 Elsevier Inc. All rights reserved. C1 [Piris, Adriano; Duncan, Lyn M.] Massachusetts Gen Hosp, Dermatopathol Unit, Pathol Serv, Boston, MA 02114 USA. [Piris, Adriano; Sober, Arthur J.; Tsao, Hensin; Tanabe, Kenneth K.; Duncan, Lyn M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hung, Tawny] Vancouver Gen Hosp, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada. [Hung, Tawny] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Lobo, Alice] Univ Sao Paulo, Hosp Clin, Dept Dermatol, BR-05403010 Sao Paulo, Brazil. [Mihm, Martin C., Jr.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Sober, Arthur J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Sober, Arthur J.; Tsao, Hensin] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Tanabe, Kenneth K.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. RP Duncan, LM (reprint author), Massachusetts Gen Hosp, Dermatopathol Unit, Pathol Serv, WRN 825, Boston, MA 02114 USA. EM duncan@helix.mgh.harvard.edu NR 37 TC 21 Z9 21 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD JAN PY 2013 VL 44 IS 1 BP 87 EP 94 DI 10.1016/j.humpath.2012.04.019 PG 8 WC Pathology SC Pathology GA 056PW UT WOS:000312504400010 PM 22939951 ER PT J AU Fox, ER Musani, SK Singh, P Bidulescu, A Nagarajarao, HS Samdarshi, TE Steffes, MW Wang, TJ Taylor, HA Vasan, RS AF Fox, Ervin R. Musani, Solomon K. Singh, Preeti Bidulescu, Aurelian Nagarajarao, Harsha S. Samdarshi, Tandaw E. Steffes, Michael W. Wang, Thomas J. Taylor, Herman A. Vasan, Ramachandran S. TI Association of Plasma B-Type Natriuretic Peptide Concentrations With Longitudinal Blood Pressure Tracking in African Americans Findings From the Jackson Heart Study SO HYPERTENSION LA English DT Article DE blood pressure; b-type natriuretic peptide; African Americans ID ESSENTIAL-HYPERTENSION; CARDIOVASCULAR-DISEASE; PRIMARY ALDOSTERONISM; RACIAL-DIFFERENCES; BRAIN; ATRIAL; IMPACT; HYPERTROPHY; DISPARITY; COMMUNITY AB Water and sodium retention precedes the development of high blood pressure (BP) and explains a compensatory rise in B-type natriuretic peptide (BNP) concentrations. It is unclear whether BNP concentrations antedate the BP progression. We hypothesized that higher BNP concentrations in our African American cohort will be associated with longitudinal increases in BP, progression of BP stage, and incident hypertension. Our study sample consisted of 888 normotensive (based on BP at examination 1 [2000-2004]) participants of the Jackson Heart Study (mean age, 47 +/- 12 years; 61% women). We examined the relation of BNP concentrations at the baseline examination to change in systolic and diastolic BPs, BP progression (an increase by 1 BP stage as defined by THE sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) and incident hypertension by examination 2 (2005-2008) adjusting for baseline BP stages, systolic and diastolic BPS, traditional risk factors, and echocardiographic left ventricular mass. Over a median follow-up period of 5.0 +/- 0.8 years, 36.9% progressed to a higher BP stage and 19.3% developed hypertension. In multivariable regression models, higher log-BNP concentrations at examination 1 were significantly and positively associated with changes in systolic and diastolic BPs (P<0.05 for both). Baseline log-BNP was significantly associated with BP progression (P=0.046). Every SD increase in baseline log BNP was associated with a 12% increased risk of BP progression. Log-BNP was not significantly associated with incident hypertension (P=0.12). In our community-based sample of African Americans, higher BNP concentrations predicted a longitudinal increase in systolic and diastolic BPs and progression of BP stage. (Hypertension. 2013; 61:48-54.) C1 [Fox, Ervin R.] Univ Mississippi, Med Ctr, Div Cardiovasc Dis, Dept Med, Jackson, MS 39216 USA. [Singh, Preeti] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA. [Bidulescu, Aurelian] Morehouse Sch Med, Atlanta, GA 30310 USA. [Steffes, Michael W.] Univ Minnesota, Minneapolis, MN USA. [Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Fox, ER (reprint author), Univ Mississippi, Med Ctr, Div Cardiovasc Dis, Dept Med, 2500 N State St, Jackson, MS 39216 USA. EM efox@umc.edu RI Bidulescu, Aurelian/N-2617-2014; OI Bidulescu, Aurelian/0000-0001-8211-8309; Ramachandran, Vasan/0000-0001-7357-5970 FU National Institutes of Health [N01-HC-95170, N01-HC-95171, N01-HC-95172, HL076784]; National Heart, Lung, and Blood Institute; National Center for Minority Health and Health Disparities [AG028321]; National Institute of Aging; Public Health Service Award from the Clinical and Translational Science Award program, National Institutes of Health, National Center for Research Resources [UL1 RR025008] FX The JHS is supported by National Institutes of Health contracts N01-HC-95170, N01-HC-95171, and N01-HC-95172, HL076784 provided by the National Heart, Lung, and Blood Institute and the National Center for Minority Health and Health Disparities, and AG028321 provided by the National Institute of Aging. This study was partially supported by Public Health Service Award UL1 RR025008 from the Clinical and Translational Science Award program, National Institutes of Health, National Center for Research Resources to A. Bidulescu. NR 38 TC 6 Z9 7 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JAN PY 2013 VL 61 IS 1 BP 48 EP 54 DI 10.1161/HYPERTENSIONAHA.112.197657 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 055AD UT WOS:000312386200017 PM 23184379 ER PT J AU Darragh, TM Colgan, TJ Cox, JT Heller, DS Henry, MR Luff, RD McCalmont, T Nayar, R Palefsky, JM Stoler, MH Wilkinson, EJ Zaino, RJ Wilbur, DC AF Darragh, Teresa M. Colgan, Terence J. Cox, J. Thomas Heller, Debra S. Henry, Michael R. Luff, Ronald D. McCalmont, Timothy Nayar, Ritu Palefsky, Joel M. Stoler, Mark H. Wilkinson, Edward J. Zaino, Richard J. Wilbur, David C. CA LAST Project Work Grp TI The Lower Anogenital Squamous Terminology Standardization Project for HPV-associated Lesions: Background and Consensus Recommendations From the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE Intraepithelial neoplasia; Squamous intraepithelial lesion; Human papillomavirus; Microinvasive carcinoma; Superficially invasive carcinoma; p16; terminology ID VULVAR INTRAEPITHELIAL NEOPLASIA; RISK HUMAN-PAPILLOMAVIRUS; STAGE-IA CARCINOMA; SUPERFICIALLY INVASIVE-CARCINOMA; IMPROVES INTEROBSERVER AGREEMENT; DIAGNOSTIC SURGICAL PATHOLOGY; BETHESDA SYSTEM TERMINOLOGY; ADENOCARCINOMA IN-SITU; CELL CARCINOMA; MICROINVASIVE CARCINOMA AB The terminology for human papillomavirus (HPV)-associated squamous lesions of the lower anogenital tract has a long history marked by disparate diagnostic terms derived from multiple specialties. It often does not reflect current knowledge of HPV biology and pathogenesis. A consensus process was convened to recommend terminology unified across lower anogenital sites. The goal was to create a histopathologic nomenclature system that reflects current knowledge of HPV biology, optimally uses available biomarkers, and facilitates clear communication across different medical specialties. The Lower Anogenital Squamous Terminology (LAST) project was co-sponsored by the College of American Pathologists (CAP) and the American Society for Colposcopy and Cervical Pathology (ASCCP) and included 5 working groups; three work groups performed comprehensive literature reviews and developed draft recommendations. Another work group provided the historical background and the fifth will continue to foster implementation of the LAST recommendations. After an open comment period, the draft recommendations were presented at a consensus conference attended by LAST work group members, advisors and representatives from 35 stakeholder organizations including professional societies and government agencies. Recommendations were finalized and voted upon at the consensus meeting. The final approved recommendations standardize biologically-relevant histopathologic terminology for HPV-associated squamous intraepithelial lesions and superficially invasive squamous carcinomas across all lower anogenital tract sites and detail appropriate use of specific biomarkers to clarify histologic interpretations and enhance diagnostic accuracy. A plan for disseminating and monitoring recommendation implementation in the practicing community was also developed. The implemented recommendations will facilitate communication between pathologists and their clinical colleagues and improve accuracy of histologic diagnosis with the ultimate goal of providing optimal patient care. C1 [Darragh, Teresa M.] UCSF, Mt Zion Med Ctr, Dept Pathol, San Francisco, CA 94115 USA. [Colgan, Terence J.] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Cox, J. Thomas] Univ Calif Santa Barbara, Student Hlth Serv, Santa Barbara, CA 93106 USA. [Heller, Debra S.] UMDNJ, New Jersey Med Sch, Newark, NJ USA. [Henry, Michael R.] Mayo Clin, Rochester, MN USA. [Luff, Ronald D.] Quest Diagnost, Teterboro, NJ USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Nayar, Ritu] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Stoler, Mark H.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Wilkinson, Edward J.] Univ Florida, Coll Med, Gainesville, FL USA. [Zaino, Richard J.] Penn State Univ, Milton S Hershey Med Ctr, Hershey, PA 17033 USA. [Wilbur, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Darragh, TM (reprint author), UCSF, Mt Zion Med Ctr, Dept Pathol, 1600 Divisadero St,Room B618, San Francisco, CA 94115 USA. EM teresa.darragh@ucsf.edu RI Colgan, Terence/J-2339-2016 FU ASCCP; CAP FX ASCCP and the CAP provided the funding for this project; no industry funds were used in the development of the consensus statements and recommendations. NR 181 TC 88 Z9 99 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JAN PY 2013 VL 32 IS 1 BP 76 EP 115 DI 10.1097/PGP.0b013e31826916c7 PG 40 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 057KM UT WOS:000312562100012 PM 23202792 ER PT J AU Akgun, KM Gordon, K Pisani, M Fried, T McGinnis, KA Tate, JP Butt, AA Gibert, CL Huang, L Rodriguez-Barradas, MC Rimland, D Justice, AC Crothers, K AF Akguen, Kathleen M. Gordon, Kirsha Pisani, Margaret Fried, Terri McGinnis, Kathleen A. Tate, Janet P. Butt, Adeel A. Gibert, Cynthia L. Huang, Laurence Rodriguez-Barradas, Maria C. Rimland, David Justice, Amy C. Crothers, Kristina TI Risk Factors for Hospitalization and Medical Intensive Care Unit (MICU) Admission Among HIV-Infected Veterans SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; hospitalization; medical intensive care unit (MICU); aging; VACS index; comorbidity ID ACTIVE ANTIRETROVIRAL THERAPY; QUALITY-OF-LIFE; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; LONG-TERM SURVIVAL; CRITICALLY-ILL; NEGATIVE VETERANS; CIGARETTE-SMOKING; ADULT PATIENTS; MORTALITY; IMPACT AB Objective: With improved survival of HIV-infected persons on antiretroviral therapy and growing prevalence of non-AIDS diseases, we asked whether the VACS Index, a composite measure of HIV-associated and general organ dysfunction predictive of all-cause mortality, predicts hospitalization and medical intensive care unit (MICU) admission. We also asked whether AIDS and non-AIDS conditions increased risk after accounting for VACS Index score. Methods: We analyzed data from the Veterans Aging Cohort Study (VACS), a prospective study of HIV-infected Veterans receiving care between 2002 and 2008. Data were obtained from the electronic medical record, VA administrative databases, and patient questionnaires and were used to identify comorbidities and calculate baseline VACS Index scores. The primary outcome was first hospitalization within 2 years of VACS enrollment. We used multivariable Cox regression to determine risk factors associated with hospitalization and logistic regression to determine risk factors for MICU admission, given hospitalization. Results: Of 3410 patients, 1141 were hospitalized within 2 years; 203 (17.8%)/1141 patients included an MICU admission. Median VACS Index scores were 25 (no hospitalization), 34 (hospitalization only), and 51 (MICU). In adjusted analyses, a 5-point increment in VACS Index score was associated with 10% higher risk of hospitalization and MICU admission. In addition to VACS Index score, Hispanic ethnicity, current smoking, hazardous alcohol use, chronic obstructive pulmonary disease, hypertension, diabetes, and prior AIDS-defining event predicted hospitalization. Among those hospitalized, VACS Index score, cardiac disease, and prior cancer predicted MICU admission. Conclusions: The VACS Index predicted hospitalization and MICU admission as did current smoking, hazardous alcohol use, and AIDS and certain non-AIDS diagnoses. C1 [Akguen, Kathleen M.] Yale Univ, Sch Med, Sect Pulm Crit Care & Sleep Med, Dept Internal Med, New Haven, CT 06510 USA. [Akguen, Kathleen M.; Gordon, Kirsha; Tate, Janet P.; Justice, Amy C.] VA Connecticut Healthcare Syst, Dept Internal Med, West Haven, CT USA. [Fried, Terri] VA Connecticut Healthcare Syst, Clin Epidemiol Res Ctr, West Haven, CT USA. [McGinnis, Kathleen A.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Butt, Adeel A.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. [Butt, Adeel A.] Sheikh Khalifa Med City, Dept Med, Abu Dhabi, U Arab Emirates. [Gibert, Cynthia L.] Vet Affairs Med Ctr, Dept Med, Washington, DC 20422 USA. [Gibert, Cynthia L.] George Washington Univ, Washington, DC USA. [Huang, Laurence] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Rodriguez-Barradas, Maria C.] Michael E DeBakey VA Med Ctr, Infect Dis Sect, Houston, TX USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Rimland, David] Atlanta VA Med Ctr, Atlanta, GA USA. [Rimland, David] Emory Univ, Sch Med, Dept Med, Atlanta, GA USA. [Crothers, Kristina] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. RP Akgun, KM (reprint author), Yale Univ, Sch Med, Sect Pulm Crit Care & Sleep Med, Dept Internal Med, LCI 106,15 York St, New Haven, CT 06510 USA. EM kathleen.akgun@yale.edu RI Andrade, Hugo/M-6631-2013; OI Andrade, Hugo/0000-0001-6781-6125; Crothers, Kristina/0000-0001-9702-0371 FU Association of Subspecialty Physicians; CHEST Foundation of American College of Chest Physicians T. Franklin Williams Award; National Institute of Health [K24 Hl087713]; National Institute on Alcohol Abuse and Alcoholism [5U01AA013566-05]; National Heart, Lung, and Blood Institute [R01 HL090342] FX Supported by the Association of Subspecialty Physicians and CHEST Foundation of the American College of Chest Physicians T. Franklin Williams Award (K. M. Akgun); National Institute of Health Grant K24 Hl087713 (L. Huang); National Institute on Alcohol Abuse and Alcoholism Grant 5U01AA013566-05 (A. C. Justice); National Institutes of Health; National Heart, Lung, and Blood Institute Grant R01 HL090342 (K. Crothers). NR 50 TC 32 Z9 32 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2013 VL 62 IS 1 BP 52 EP 59 DI 10.1097/QAI.0b013e318278f3fa PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 058PG UT WOS:000312645400015 PM 23111572 ER PT J AU Desmonde, S Coffie, PA Aka, EA Amani-Bosse, C Messou, E Dabis, F Ciaranello, A Leroy, V AF Desmonde, Sophie Coffie, Patrick A. Aka, Edmond A. Amani-Bosse, Clarisse Messou, Eugene Dabis, Francois Ciaranello, Andrea Leroy, Valeriane TI Health Care Resource Utilization in Untreated HIV-Infected Children in A Pediatric Programme, Abidjan, Cote d'Ivoire, 2004-2009 SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; pediatrics; health care resource utilization; morbidity; West Africa ID 4 AFRICAN COUNTRIES; ANTIRETROVIRAL THERAPY; LIMITED SETTINGS; SEVERE MORBIDITY; WESTERN KENYA; SCALING-UP; COTRIMOXAZOLE; DETERMINANTS; TRANSMISSION; MORTALITY AB Background: We describe health care resource utilization among HIV-1-infected children who have not yet undergone antiretroviral treatment (ART) in Abidjan, Cote d'Ivoire. Methods: HIV-infected children enrolled prospectively in an HIV care programme in 2 health facilities in Abidjan (2004-2009) were followed up from date of inclusion until database closeout, death, ART initiation, or loss to follow-up (no clinical contact for more than 6 months). Incidences of health care resource utilization (outpatient care, inpatient day care, and hospitalization) were described according to severe morbidity and mixed effect log linear models were computed to identify associated factors. Results: Overall, 405 children were included, entering care at a median age of 4.5 years, 66.9% were receiving cotrimoxazole prophylaxis, and 27.7% met 2006 WHO criteria for immunodeficiency by age. The median follow-up time was 11.6 months (interquartile range: 1.4; 30.7). Overall, 371 clinical events occurred in 162 children yielding to an incidence rate (IR) of 60.9/100 childyears (CY) [95% confidence interval (CI): 55.1 to 67.2]: 57% of clinical events led to outpatient care (IR: 33/100 CY), 38% to inpatient day care (IR: 22/100 CY), and 10% to hospitalization (IR: 5.9/100 CY). Further medical examinations were made allowing confirmed diagnoses in 40% of those (IR: 22.4/100 CY). Outpatient care was less common among immunodeficient children than those not (relative risk [RR] = 0.32, 95% CI: 0.18 to 0.56), in those whose main caregivers are both parents compared with those who are primarily cared for by their mother only (RR = 0.34, 95% CI: 0.15 to 0.77). Conclusion: Untreated HIV-infected children require substantial inpatient and outpatient care in a context where ART is scaling up but still not available to all. C1 [Desmonde, Sophie; Dabis, Francois; Leroy, Valeriane] Univ Bordeaux, Epidemiol Biostat U897, Ctr INSERM, ISPED, Bordeaux, France. [Coffie, Patrick A.; Amani-Bosse, Clarisse] CHU Treichville, Programme PAC CI, Abidjan, Cote Ivoire. [Aka, Edmond A.; Messou, Eugene] ACONDA, Ctr Prise Charge Rech & Format, Abidjan, Cote Ivoire. [Amani-Bosse, Clarisse] ACONDA, MTCT Plus Initiat, Abidjan, Cote Ivoire. [Ciaranello, Andrea] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Desmonde, S (reprint author), Univ Bordeaux 2, Equipe VIH Canc & Sante Globale Pays Ressources L, Inst Sante Publ Epidemiol & Dev, Ctr Rech,INSERM,U897, Case 11,146 Rue Leo Saignat, F-33076 Bordeaux, France. EM sophie.desmonde@isped.u-bordeaux2.fr RI Leroy, Valeriane/F-8129-2013 OI Leroy, Valeriane/0000-0003-3542-8616 FU US National Institutes of Health: National Institute of Allergy and Infectious Diseases Grants [R01 A1058736, 5U01AI09919-01-05, R01AI05873, K01AI078754] FX Supported in part by the US National Institutes of Health: National Institute of Allergy and Infectious Diseases Grants R01 A1058736, 5U01AI09919-01-05 (IeDEA West Africa), R01AI05873, and K01AI078754. S. Desmonde is a fellow of the Ecole des Hautes Etudes en Sante Publique, Rennes, France. The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of any of the institutions mentioned above. NR 41 TC 3 Z9 3 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2013 VL 62 IS 1 BP E14 EP E21 DI 10.1097/QAI.0b013e3182739c95 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 058PG UT WOS:000312645400003 PM 23262977 ER PT J AU O'Bryant, SE Johnson, L Balldin, V Edwards, M Barber, R Williams, B Devous, M Cushings, B Knebl, J Hall, J AF O'Bryant, Sid E. Johnson, Leigh Balldin, Valerie Edwards, Melissa Barber, Robert Williams, Benjamin Devous, Michael Cushings, Blair Knebl, Janice Hall, James TI Characterization of Mexican Americans with Mild Cognitive Impairment and Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; cognition; depression; diabetes; Hispanic; Mexican American; mild cognitive impairment ID RATING-SCALE SUM; PROJECT FRONTIER; APOLIPOPROTEIN-E; ETHNICALLY DIVERSE; NATIONAL INSTITUTE; DEMENTIA; MEMORY; SAMPLE; RISK; ASSOCIATION AB The purpose of the study was to provide characterization of Mexican Americans who meet criteria for Alzheimer's disease (AD) and mild cognitive impairment (MCI). For the study, 1,069 participants ages 40 and above who self-identified as either non-Hispanic white (n = 633) or Mexican American (n = 436) were recruited using a community-based participatory research approach. Global cognition was assessed via the Mini-Mental State Examination (MMSE), dementia severity by the Clinical Dementia Rating Scale, and depression via the Geriatric Depression Scale 30-item version. Age, gender, education, ApoE epsilon 4 allele frequency, and diabetic diagnoses were also analyzed. The findings showed that Mexican Americans (normal controls, MCI, and AD) were younger, less highly educated, performed more poorly on the MMSE, endorsed more symptoms of depression, were more likely to be diagnosed with diabetes, and possessed the ApoE epsilon 4 allele less frequently. Age was the only significant risk factor for cognitive dysfunction (AD/MCI) among Mexican Americans (OR = 1.06, 95% CI = 1.03-1.09). Age (B = 0.07, std = 0.02, p < 0.001) and ApoE epsilon 4 presence (B = 0.9, std = 0.4, p = 0.02) were significantly related to increased disease severity. Given the rapidly growing and aging Mexican American population, there is a substantial need for research into cognitive aging, MCI, and AD among this ethnic group. The current findings hold important implications for both clinic and research settings and point to additional research needs. C1 [O'Bryant, Sid E.; Johnson, Leigh; Edwards, Melissa; Knebl, Janice] Univ N Texas, Dept Internal Med, Hlth Sci Ctr, Ft Worth, TX 76107 USA. [O'Bryant, Sid E.; Johnson, Leigh; Barber, Robert; Hall, James] Univ N Texas, Hlth Sci Ctr, Inst Aging & Alzheimers Dis Res, Ft Worth, TX 76107 USA. [Balldin, Valerie] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Edwards, Melissa] Univ N Texas, Dept Clin Hlth Psychol, Denton, TX 76203 USA. [Barber, Robert] Univ N Texas, Hlth Sci Ctr, Dept Pharmacol & Neurosci, Ft Worth, TX 76107 USA. [Williams, Benjamin] Univ Texas SW Med Ctr Dallas, Dept Neurol & Neurotherapeut, Dallas, TX 75390 USA. [Devous, Michael] Univ Texas SW Med Ctr Dallas, Dept Radiol, Dallas, TX 75390 USA. [Cushings, Blair] Univ N Texas, Texas Coll Osteopath Med, Hlth Sci Ctr, Ft Worth, TX 76107 USA. [Hall, James] Univ N Texas, Dept Psychiat, Hlth Sci Ctr, Ft Worth, TX 76107 USA. RP O'Bryant, SE (reprint author), Univ N Texas, Dept Internal Med, Hlth Sci Ctr, 3500 Camp Bowie Blvd, Ft Worth, TX 76107 USA. EM Sid.O'Bryant@unthsc.edu OI O'Bryant, Sid/0000-0003-0582-5266 FU National Institutes of Health [R01AG039389, P30AG12300, L60MD001849]; state of Texas through the Texas Council on Alzheimer's Disease and Related Disorders; Hogg Foundation for Mental Health [JRG-040, JRG-149]; Environmental Protection Agency [RD834794] FX Research reported in this publication was supported by the National Institutes of Health under award numbers R01AG039389, P30AG12300, and L60MD001849. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This study was made possible by the Texas Alzheimer's Research and Care Consortium (TARCC) funded by the state of Texas through the Texas Council on Alzheimer's Disease and Related Disorders. This research was also funded in part by grants from the Hogg Foundation for Mental Health (JRG-040 and JRG-149) and the Environmental Protection Agency (RD834794). We would like to thank all of the participants of Project FRONTIER and the TARCC along with the incredible support staff that make this study possible. NR 40 TC 15 Z9 16 U1 0 U2 5 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2013 VL 33 IS 2 BP 373 EP 379 DI 10.3233/JAD-2012-121420 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 057XR UT WOS:000312598300010 PM 22976076 ER PT J AU Kearney, DJ McDermott, K Malte, C Martinez, M Simpson, TL AF Kearney, David J. McDermott, Kelly Malte, Carol Martinez, Michelle Simpson, Tracy L. TI Effects of Participation in a Mindfulness Program for Veterans With Posttraumatic Stress Disorder: A Randomized Controlled Pilot Study SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE mindfulness; posttraumatic stress disorder; acceptance; depression; meditation ID QUALITY-OF-LIFE; COGNITIVE-PROCESSING THERAPY; NATIONAL COMORBIDITY SURVEY; CLINICAL-SIGNIFICANCE; ANXIETY DISORDERS; DEPRESSIVE SYMPTOMS; THOUGHT SUPPRESSION; PROLONGED EXPOSURE; CONTROLLED-TRIAL; MEDITATION AB Objective To assess outcomes associated with Mindfulness-Based Stress Reduction (MBSR) for veterans with PTSD. MethodsForty-seven veterans with posttraumatic stress disorder (PTSD; 37 male, 32 Caucasian) were randomized to treatment as usual (TAU; n = 22), or MBSR plus TAU (n = 25). PTSD, depression, and mental health-related quality of life (HRQOL) were assessed at baseline, posttreatment, and 4-month follow-up. Standardized effect sizes and the proportion with clinically meaningful changes in outcomes were calculated. ResultsIntention-to-treat analyses found no reliable effects of MBSR on PTSD or depression. Mental HRQOL improved posttreatment but there was no reliable effect at 4 months. At 4-month follow-up, more veterans randomized to MBSR had clinically meaningful change in mental HRQOL, and in both mental HRQOL and PTSD symptoms. Completer analyses (= 4 classes attended) showed medium to large between group effect sizes for depression, mental HRQOL, and mindfulness skills. ConclusionsAdditional studies are warranted to assess MBSR for veterans with PTSD. C1 [Kearney, David J.; McDermott, Kelly; Malte, Carol; Martinez, Michelle; Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Kearney, DJ (reprint author), Seattle VAMC 111GI,1660 S Columbian Way, Seattle, WA 98108 USA. EM david.kearney@va.gov NR 56 TC 36 Z9 36 U1 16 U2 72 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD JAN PY 2013 VL 69 IS 1 BP 14 EP 27 DI 10.1002/jclp.21911 PG 14 WC Psychology, Clinical SC Psychology GA 056JO UT WOS:000312484800002 PM 22930491 ER PT J AU Saboo, SS Di Salvo, D AF Saboo, Sachin S. Di Salvo, Donald TI Perineural cysts resembling complex cystic adnexal masses on transvaginal sonography SO JOURNAL OF CLINICAL ULTRASOUND LA English DT Article DE adnexal masses; perineural cyst; transvaginal sonography; pelvis ID TARLOV CYSTS AB Perineural cysts may be discovered incidentally on pelvic sonography and can easily mimic more common gynecologic masses. We report the complex cystic adnexal mass like appearance of these incidentally noted cysts which mimicked malignancy on sonography in a postmenopausal female, with stage I breast cancer and vaginal spotting. (C) 2011 Wiley Periodicals, Inc. J Clin Ultrasound 2013; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jcu.20899 C1 [Saboo, Sachin S.] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Saboo, SS (reprint author), Dana Farber Canc Inst, Dept Radiol, 44 Binney St, Boston, MA 02115 USA. NR 8 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0091-2751 J9 J CLIN ULTRASOUND JI J. Clin. Ultrasound PD JAN PY 2013 VL 41 IS 1 BP 55 EP 58 DI 10.1002/jcu.20899 PG 4 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 057BK UT WOS:000312536600008 PM 22105304 ER PT J AU Cheriyan, T Neuhaus, V Mudgal, CS AF Cheriyan, T. Neuhaus, V. Mudgal, C. S. TI Bony avulsion injury of flexor digitorum profundus - description of a new subtype SO JOURNAL OF HAND SURGERY-EUROPEAN VOLUME LA English DT Letter C1 [Cheriyan, T.; Neuhaus, V.; Mudgal, C. S.] Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA. RP Cheriyan, T (reprint author), Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA. EM cmudgal@partners.org NR 3 TC 1 Z9 1 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1753-1934 J9 J HAND SURG-EUR VOL JI J. Hand Surg.-Eur. Vol. PD JAN PY 2013 VL 38E IS 1 BP 91 EP 92 DI 10.1177/1753193412445140 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 056KY UT WOS:000312489300024 PM 22526514 ER PT J AU Conrad, C Fernandez-Del Castillo, C AF Conrad, Claudius Fernandez-Del Castillo, Carlos TI Preoperative evaluation and management of the pancreatic head mass SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Review DE pancreatic head mass; pancreatic cancer; diagnosis; biliary drainage; autoimmune pancreatitits ID FINE-NEEDLE ASPIRATION; AUTOIMMUNE PANCREATITIS; CLINICAL UTILITY; NEUROENDOCRINE TUMORS; MULTIDETECTOR CT; BILIARY DRAINAGE; CHROMOGRANIN-A; SERUM IGG4; RT-PCR; CANCER AB The differential diagnosis of a pancreatic head mass encompasses a wide range of clinical entities that include both solid and cystic lesions. This chapter focuses on our approach to the patient presenting with a newly found pancreatic head mass with the main goals of determining the risk of the lesion being malignant or premalignant, resectability if the patient is appropriate for surgical intervention, assessment of need for multimodality treatment and determination the patient's surgical risk. J. Surg. Oncol. 2013;107:2332. (c) 2012 Wiley Periodicals, Inc. C1 [Conrad, Claudius; Fernandez-Del Castillo, Carlos] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Conrad, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 55 Fruit St,Yawkey 7, Boston, MA 02115 USA. EM cconrad@partners.org NR 92 TC 4 Z9 4 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD JAN PY 2013 VL 107 IS 1 SI SI BP 23 EP 32 DI 10.1002/jso.23165 PG 10 WC Oncology; Surgery SC Oncology; Surgery GA 057CJ UT WOS:000312539200004 PM 22674403 ER PT J AU Ghoshhajra, BB Engel, LC Karolyi, M Sidhu, MS Wai, B Barreto, M Shanmugam, U Hoffmann, U Brady, TJ Kalra, M Abbara, S AF Ghoshhajra, Brian B. Engel, Leif-Christopher Karolyi, Mihaly Sidhu, Manavjot Singh Wai, Bryan Barreto, Mitya Shanmugam, Uthamalingam Hoffmann, Udo Brady, Thomas J. Kalra, Manudeep Abbara, Suhny TI Cardiac Computed Tomography Angiography With Automatic Tube Potential Selection Effects on Radiation Dose and Image Quality SO JOURNAL OF THORACIC IMAGING LA English DT Article DE cardiac computed tomography angiography; radiation dose; image quality; automatic tube potential; tube current selection ID CORONARY CT ANGIOGRAPHY; CURRENT MODULATION; EXPOSURE CONTROL; OPTIMIZATION; NOISE; ATTENUATION; REDUCTION; ABDOMEN; PELVIS; TRIAL AB Purpose: Automatic exposure control (AEC) algorithms are widely available in coronary computed tomography angiography (CTA) and have been shown to reduce radiation doses by adjusting tube current to patient size. However, the effects of anthropometry-based automatic potential selection (APS) on image quality and radiation dose are unknown. We sought to investigate the effect of an APS algorithm on coronary CTA radiation dose and image quality. Materials and Methods: For this retrospective case-control study we selected 38 patients who had undergone coronary CTA for coronary artery assessment in whom tube potential and tube current were selected automatically by a combined automatic tube potential and tube current selection algorithm (APS-AEC) and compared them with 38 controls for whom tube voltage was selected according to standard body mass index (BMI) cutoffs and tube current was selected using automatic exposure control (BMI-AEC). Controls were matched for BMI, heart rate, heart rhythm, sex, acquisition mode, and indication for cardiac CTA. Image quality was assessed as contrast-to-noise ratio and signal-to-noise ratio in the proximal coronary arteries. Subjective reader assessment was also made. Total radiation dose (volume-weighted computed tomography dose index) was measured and compared between the 2 groups. In the study group, comparison was made with conventional BMI-guided prior protocols (site protocols and Society of Cardiovascular Computed Tomography recommendations) through disagreement analysis. Results: The APS-AEC cases received 29.8% lower overall radiation dose compared with controls (P = not significant). APS-AEC resulted in a significantly higher signal-to-noise ratio of the proximal coronary arteries (P < 0.01) and contrast-to-noise ratio of the left main (P = 0.01). In the study cases, the APS resulted in a change in tube potential versus site protocols and Society of Cardiovascular Computed Tomography recommendations in 45% (n = 17) and 50% (n = 19) of patients, respectively. Conclusion: Automated tube potential selection software resulted in significantly improved objective image quality versus standard BMI-based methods of tube potential selection, without increased radiation doses. C1 [Ghoshhajra, Brian B.; Engel, Leif-Christopher; Karolyi, Mihaly; Sidhu, Manavjot Singh; Wai, Bryan; Shanmugam, Uthamalingam; Hoffmann, Udo; Brady, Thomas J.; Kalra, Manudeep; Abbara, Suhny] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Dept Radiol, Boston, MA 02114 USA. [Ghoshhajra, Brian B.; Engel, Leif-Christopher; Karolyi, Mihaly; Sidhu, Manavjot Singh; Wai, Bryan; Shanmugam, Uthamalingam; Hoffmann, Udo; Brady, Thomas J.; Kalra, Manudeep; Abbara, Suhny] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Barreto, Mitya] Siemens Healthcare, Malvern, PA USA. RP Ghoshhajra, BB (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, Dept Radiol, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM bghoshhajra@partners.org NR 29 TC 21 Z9 25 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0883-5993 J9 J THORAC IMAG JI J. Thorac. Imaging PD JAN PY 2013 VL 28 IS 1 BP 40 EP 48 DI 10.1097/RTI.0b013e3182631e8a PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 057IH UT WOS:000312556000012 PM 22847638 ER PT J AU Khanna, A Hu, JC Gu, XM Nguyen, PL Lipsitz, S Palapattu, GS AF Khanna, Abhinav Hu, Jim C. Gu, Xiangmei Nguyen, Paul L. Lipsitz, Stuart Palapattu, Ganesh S. TI Certificate of Need Programs, Intensity Modulated Radiation Therapy Use and the Cost of Prostate Cancer Care SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; radiotherapy; intensity-modulated; health care costs; certificate of need ID ACUTE MYOCARDIAL-INFARCTION; RADICAL PROSTATECTOMY; REGULATIONS; REVASCULARIZATION; AVAILABILITY; EXPENDITURES; MORBIDITY; SURGEONS; OUTCOMES; IMPACT AB Purpose: Certificate of need programs are a primary mechanism to regulate the use and cost of health care services at the state level. The effect of certificate of need programs on the use of intensity modulated radiation therapy and the increasing costs of prostate cancer care is unknown. We compared the use of intensity modulated radiation therapy and change in prostate cancer health care costs in regions with vs without active certificate of need programs. Materials and Methods: This population based, observational study using SEER (Surveillance, Epidemiology, and End Results)-Medicare linked data from 2002 through 2009 was comprised of 13,814 men treated for prostate cancer in 3 regions with active certificate of need programs (CON Yes) vs 44,541 men treated for prostate cancer in 9 regions without active certificate of need programs (CON No). We assessed intensity modulated radiation therapy use relative to other prostate cancer definitive therapies and overall prostate cancer health care costs with respect to certificate of need status. Results: In propensity score adjusted analyses, intensity modulated radiation therapy use increased from 2.3% to 46.4% of prostate cancer definitive therapies in CON Yes regions vs 11.3% to 41.7% in CON No regions from 2002 to 2009. Furthermore, we observed greater intensity modulated radiation therapy use with time in CON Yes vs No regions (p < 0.001). Annual cost growth did not differ between CON Yes vs No regions (p = 0.396). Conclusions: Certificate of need programs were not effective in limiting intensity modulated radiation therapy use or attenuating prostate cancer health care costs. There remains an unmet need to control the rapid adoption of new, more expensive therapies for prostate cancer that have limited cost and comparative effectiveness data. C1 [Palapattu, Ganesh S.] Methodist Hosp, Weill Cornell Med Coll, Dept Urol, Houston, TX 77030 USA. [Khanna, Abhinav] Baylor Coll Med, Houston, TX 77030 USA. [Hu, Jim C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Inst Urol Oncol, Los Angeles, CA 90095 USA. [Gu, Xiangmei; Lipsitz, Stuart] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Nguyen, Paul L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Palapattu, GS (reprint author), Univ Michigan, Dept Urol, 3875 TC SPC 5330,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM gpalapat@med.umich.edu FU Astellas/AUA Foundation Rising Star in Urology Award FX Recipient of Astellas/AUA Foundation Rising Star in Urology Award. NR 30 TC 5 Z9 5 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JAN PY 2013 VL 189 IS 1 BP 75 EP 79 DI 10.1016/j.juro.2012.08.181 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 057ZZ UT WOS:000312604800026 PM 23164382 ER PT J AU Shah, VB Shi, J Hout, DR Oztop, I Krishnan, L Ahn, J Shotwell, MS Engelman, A Aiken, C AF Shah, Vaibhav B. Shi, Jiong Hout, David R. Oztop, Ilker Krishnan, Lavanya Ahn, Jinwoo Shotwell, Matthew S. Engelman, Alan Aiken, Christopher TI The Host Proteins Transportin SR2/TNPO3 and Cyclophilin A Exert Opposing Effects on HIV-1 Uncoating SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; OLD-WORLD MONKEY; NUCLEAR IMPORT; RESTRICTION FACTORS; REVERSE TRANSCRIPTION; SR PROTEINS; HUMAN-CELLS; IN-VIVO; INFECTION; REPLICATION AB Following entry of the HIV-1 core into target cells, productive infection depends on the proper disassembly of the viral capsid (uncoating). Although much is known regarding HIV-1 entry, the actions of host cell proteins that HIV-1 utilizes during early postentry steps are poorly understood. One such factor, transportin SR2 (TRN-SR2)/transportin 3 (TNPO3), promotes infection by HIV-1 and some other lentiviruses, and recent studies have genetically linked TNPO3 dependence of infection to the viral capsid protein (CA). Here we report that purified recombinant TNPO3 stimulates the uncoating of HIV-1 cores in vitro. The stimulatory effect was reduced by RanGTP, a known ligand for transportin family members. Depletion of TNPO3 in target cells rendered HIV-1 less susceptible to inhibition by PF74, a small-molecule HIV-1 inhibitor that induces premature uncoating. In contrast to the case for TNPO3, addition of the CA-binding host protein cyclophilin A (CypA) inhibited HIV-1 uncoating and reduced the stimulatory effect of TNPO3 on uncoating in vitro. In cells in which TNPO3 was depleted, HIV-1 infection was enhanced 4-fold by addition of cyclosporine, indicating that the requirement for TNPO3 in HIV-1 infection is modulated by CypA-CA interactions. Although TNPO3 was localized primarily to the cytoplasm, depletion of TNPO3 from target cells inhibited HIV-1 infection without reducing the accumulation of nuclear proviral DNA, suggesting that TNPO3 facilitates a stage of the virus life cycle subsequent to nuclear entry. Our results suggest that TNPO3 and cyclophilin A facilitate HIV-1 infection by coordinating proper uncoating of the core in target cells. C1 [Shah, Vaibhav B.; Shi, Jiong; Hout, David R.; Aiken, Christopher] Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37212 USA. [Oztop, Ilker; Krishnan, Lavanya; Engelman, Alan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Oztop, Ilker; Krishnan, Lavanya; Engelman, Alan] Harvard Univ, Sch Med, Div Aids, Boston, MA USA. [Ahn, Jinwoo] Univ Pittsburgh, Sch Med, Dept Biol Struct, Pittsburgh, PA USA. [Shotwell, Matthew S.] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37212 USA. RP Aiken, C (reprint author), Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37212 USA. EM chris.aiken@vanderbilt.edu OI Hout, David/0000-0001-8897-3963 FU NIH [AI076121, GM082251, AI052014] FX This work was supported by NIH grants AI076121 (C.A.), GM082251 (J.A.), and AI052014 (A.E.). NR 68 TC 54 Z9 54 U1 0 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2013 VL 87 IS 1 BP 422 EP 432 DI 10.1128/JVI.07177-11 PG 11 WC Virology SC Virology GA 055ZB UT WOS:000312455500037 PM 23097435 ER PT J AU Koh, Y Wu, XL Ferris, AL Matreyek, KA Smith, SJ Lee, K KewalRamani, VN Hughes, SH Engelman, A AF Koh, Yasuhiro Wu, Xiaolin Ferris, Andrea L. Matreyek, Kenneth A. Smith, Steven J. Lee, KyeongEun KewalRamani, Vineet N. Hughes, Stephen H. Engelman, Alan TI Differential Effects of Human Immunodeficiency Virus Type 1 Capsid and Cellular Factors Nucleoporin 153 and LEDGF/p75 on the Efficiency and Specificity of Viral DNA Integration SO JOURNAL OF VIROLOGY LA English DT Article ID PREINTEGRATION COMPLEXES; HIV-1 INTEGRASE; NUCLEAR IMPORT; HUMAN GENOME; REVERSE TRANSCRIPTION; NONDIVIDING CELLS; TARGET SITES; IN-VIVO; REPLICATION; INFECTION AB Retroviruses integrate into cellular DNA nonrandomly. Lentiviruses such as human immunodeficiency virus type 1 (HIV-1) favor the bodies of active genes and gene-enriched transcriptionally active regions of chromosomes. The interaction between lentiviral integrase and the cellular protein lens epithelium-derived growth factor (LEDGF)/p75 underlies the targeting of gene bodies, whereas recent research has highlighted roles for the HIV-1 capsid (CA) protein and cellular factors implicated in viral nuclear import, including transportin 3 (TNPO3) and nucleoporin 358 (NUP358), in the targeting of gene-dense regions of chromosomes. Here, we show that CA mutations, which include the substitution of Asp for Asn74 (N74D), significantly reduce the dependency of HIV-1 on LEDGF/p75 during infection and that this difference correlates with the efficiency of viral DNA integration. The distribution of integration sites mapped by Illumina sequencing confirms that the N74D mutation reduces integration into gene-rich regions of chromosomes and gene bodies and reveals previously unrecognized roles for NUP153 (another HIV-1 cofactor implicated in viral nuclear import) and LEDGF/p75 in the targeting of the viral preintegration complex to gene-dense regions of chromatin. A role for the CA protein in determining the dependency of HIV-1 on LEDGF/p75 during infection highlights a connection between the viral capsid and chromosomal DNA integration. C1 [Koh, Yasuhiro; Matreyek, Kenneth A.; Engelman, Alan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Koh, Yasuhiro; Matreyek, Kenneth A.; Engelman, Alan] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Wu, Xiaolin] Frederick Natl Lab Canc Res, SAIC Frederick Inc, Lab Mol Technol, Frederick, MD USA. [Ferris, Andrea L.; Smith, Steven J.; Lee, KyeongEun; KewalRamani, Vineet N.; Hughes, Stephen H.] Frederick Natl Lab Canc Res, HIV Drug Resistance Program, Frederick, MD USA. RP Engelman, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM alan_engelman@dfci.harvard.edu OI Matreyek, Kenneth/0000-0001-9149-551X FU National Cancer Institute's Intramural Center for Cancer Research; National Institutes of Health (NIH) [AI039394, AI052014] FX This work was supported by the National Cancer Institute's Intramural Center for Cancer Research, which supports the HIV Drug Resistance Program (V.N.K. and S.H.H.), and National Institutes of Health (NIH) grants AI039394 and AI052014 (to A.E.). NR 66 TC 40 Z9 40 U1 0 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2013 VL 87 IS 1 BP 648 EP 658 DI 10.1128/JVI.01148-12 PG 11 WC Virology SC Virology GA 055ZB UT WOS:000312455500057 PM 23097450 ER PT J AU Knapp, S Arruda, P Blagg, J Burley, S Drewry, DH Edwards, A Fabbro, D Gillespie, P Gray, NS Kuster, B Lackey, KE Mazzafera, P Tomkinson, NCO Willson, TM Workman, P Zuercher, WJ AF Knapp, Stefan Arruda, Paulo Blagg, Julian Burley, Stephen Drewry, David H. Edwards, Aled Fabbro, Doriano Gillespie, Paul Gray, Nathanael S. Kuster, Bernhard Lackey, Karen E. Mazzafera, Paulo Tomkinson, Nicholas C. O. Willson, Timothy M. Workman, Paul Zuercher, William J. TI A public-private partnership to unlock the untargeted kinome SO NATURE CHEMICAL BIOLOGY LA English DT Article ID KINASE INHIBITOR; SELECTIVE INHIBITOR; CELL; DISCOVERY; CANCER; POTENT; ABL C1 [Knapp, Stefan] Univ Oxford, Dept Clin Pharmacol, Oxford, England. [Knapp, Stefan] Univ Oxford, Nuffield Dept Clin Med, Struct Genom Consortium, Oxford, England. [Arruda, Paulo; Mazzafera, Paulo] Univ Estadual Campinas, Inst Biol, Campinas, SP, Brazil. [Blagg, Julian; Workman, Paul] Inst Canc Res, Div Canc Therapeut, Canc Res UK Canc Therapeut Unit, London SW3 6JB, England. [Burley, Stephen] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92103 USA. [Edwards, Aled] Struct Genom Consortium, Toronto, ON, Canada. [Fabbro, Doriano] Novartis, Expertise Platform Kinases, Basel, Switzerland. [Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kuster, Bernhard] Tech Univ Munich, Munich, Germany. [Gillespie, Paul; Lackey, Karen E.] Hoffmann La Roche Inc, Pharmaceut Res & Early Dev, Nutley, NJ 07110 USA. [Tomkinson, Nicholas C. O.] Univ Strathclyde, Glasgow, Lanark, Scotland. [Drewry, David H.; Willson, Timothy M.; Zuercher, William J.] GlaxoSmithKline, Dept Biol Chem, Res Triangle Pk, NC USA. RP Knapp, S (reprint author), Univ Oxford, Dept Clin Pharmacol, Oxford, England. EM william.j.zuercher@gsk.com RI Mazzafera, Paulo/D-4766-2012; 6, INCT/H-4795-2013; Infabic, Inct/I-2128-2013; Arruda, Paulo/H-1440-2011; Kuster, Bernhard/Q-6031-2016; OI Kuster, Bernhard/0000-0002-9094-1677; Knapp, Stefan/0000-0001-5995-6494; Tomkinson, Nicholas/0000-0002-5509-0133 FU Cancer Research UK [11566]; Wellcome Trust [092809] NR 24 TC 55 Z9 55 U1 2 U2 46 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 EI 1552-4469 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD JAN PY 2013 VL 9 IS 1 BP 3 EP 7 DI 10.1038/nchembio.1113 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 056JI UT WOS:000312484200002 PM 23238671 ER PT J AU Vassoler, FM White, SL Schmidt, HD Sadri-Vakili, G Pierce, RC AF Vassoler, Fair M. White, Samantha L. Schmidt, Heath D. Sadri-Vakili, Ghazaleh Pierce, R Christopher TI Epigenetic inheritance of a cocaine-resistance phenotype SO NATURE NEUROSCIENCE LA English DT Article ID MEDIAL PREFRONTAL CORTEX; HUNTINGTONS-DISEASE; OFFSPRING VIABILITY; DNA METHYLATION; GENE-EXPRESSION; FEMALE RATS; DRUG-ABUSE; BDNF; BRAIN; MICE AB We delineated a heritable phenotype resulting from the self-administration of cocaine in rats. We observed delayed acquisition and reduced maintenance of cocaine self-administration in male, but not female, offspring of sires that self-administered cocaine. Brain-derived neurotrophic factor (Bdnf) mRNA and BDNF protein were increased in the medial prefrontal cortex (mPFC), and there was an increased association of acetylated histone H3 with Bdnf promoters in only the male offspring of cocaine-experienced sires. Administration of a BDNF receptor antagonist (the TrkB receptor antagonist ANA-12) reversed the diminished cocaine self-administration in male cocaine-sired rats. In addition, the association of acetylated histone H3 with Bdnf promoters was increased in the sperm of sires that self-administered cocaine. Collectively, these findings indicate that voluntary paternal ingestion of cocaine results in epigenetic reprogramming of the germline, having profound effects on mPFC gene expression and resistance to cocaine reinforcement in male offspring. C1 [Vassoler, Fair M.; White, Samantha L.; Schmidt, Heath D.; Pierce, R Christopher] Univ Penn, Dept Psychiat, Perelman Sch Med, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA. [Sadri-Vakili, Ghazaleh] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Boston, MA 02114 USA. RP Pierce, RC (reprint author), Univ Penn, Dept Psychiat, Perelman Sch Med, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA. EM rcpierce@mail.med.upenn.edu OI Vassoler, Fair/0000-0001-5317-7174 FU US National Institutes of Health [R01s DA15214, DA22339, DA33641, K02 DA18678, K01 DA30445, F31 DA31535, T32s DA28874, MH86599] FX We thank R. Schassburger, T. Hopkins, B. Kimmey, S. Friedman, A. Lee, S. Darnell and G. Sangrey for technical assistance, and L. Briand for advice on experimental design. This work was supported by grants from the US National Institutes of Health (R01s DA15214, DA22339, DA33641, K02 DA18678, K01 DA30445, F31 DA31535, T32s DA28874 and MH86599). NR 48 TC 94 Z9 100 U1 3 U2 67 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 EI 1546-1726 J9 NAT NEUROSCI JI Nat. Neurosci. PD JAN PY 2013 VL 16 IS 1 BP 42 EP U67 DI 10.1038/nn.3280 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 058KZ UT WOS:000312633900011 PM 23242310 ER PT J AU Froemke, RC Carcea, I Barker, AJ Yuan, K Seybold, BA Martins, ARO Zaika, N Bernstein, H Wachs, M Levis, PA Polley, DB Merzenich, MM Schreiner, CE AF Froemke, Robert C. Carcea, Ioana Barker, Alison J. Yuan, Kexin Seybold, Bryan A. Martins, Ana Raquel O. Zaika, Natalya Bernstein, Hannah Wachs, Megan Levis, Philip A. Polley, Daniel B. Merzenich, Michael M. Schreiner, Christoph E. TI Long-term modification of cortical synapses improves sensory perception SO NATURE NEUROSCIENCE LA English DT Article ID PRIMARY AUDITORY-CORTEX; SPECTROTEMPORAL RECEPTIVE-FIELDS; VISUAL-CORTEX; SYNAPTIC PLASTICITY; NUCLEUS BASALIS; DEPENDENT PLASTICITY; MAP PLASTICITY; DISCRIMINATION; STIMULATION; RAT AB Synapses and receptive fields of the cerebral cortex are plastic. However, changes to specific inputs must be coordinated within neural networks to ensure that excitability and feature selectivity are appropriately configured for perception of the sensory environment. We induced long-lasting enhancements and decrements to excitatory synaptic strength in rat primary auditory cortex by pairing acoustic stimuli with activation of the nucleus basalis neuromodulatory system. Here we report that these synaptic modifications were approximately balanced across individual receptive fields, conserving mean excitation while reducing overall response variability. Decreased response variability should increase detection and recognition of near-threshold or previously imperceptible stimuli. We confirmed both of these hypotheses in behaving animals. Thus, modification of cortical inputs leads to wide-scale synaptic changes, which are related to improved sensory perception and enhanced behavioral performance. C1 [Froemke, Robert C.; Carcea, Ioana; Martins, Ana Raquel O.; Zaika, Natalya; Bernstein, Hannah] NYU, Sch Med, Dept Physiol & Neurosci,Skirball Inst Biomol Med, Mol Neurobiol Program,Helen & Martin Kimmel Ctr B, New York, NY 10012 USA. [Froemke, Robert C.; Carcea, Ioana; Martins, Ana Raquel O.; Zaika, Natalya; Bernstein, Hannah] NYU, Sch Med, Dept Otolaryngol, New York, NY USA. [Froemke, Robert C.; Carcea, Ioana; Martins, Ana Raquel O.] NYU, Ctr Neural Sci, New York, NY 10003 USA. [Froemke, Robert C.; Barker, Alison J.; Yuan, Kexin; Seybold, Bryan A.; Merzenich, Michael M.; Schreiner, Christoph E.] Univ Calif San Francisco, Coleman Mem Lab, San Francisco, CA 94143 USA. [Froemke, Robert C.; Barker, Alison J.; Yuan, Kexin; Seybold, Bryan A.; Merzenich, Michael M.; Schreiner, Christoph E.] Univ Calif San Francisco, Dept Otolaryngol, Neurosci Grad Grp, WM Keck Fdn Ctr Integrat Neurosci, San Francisco, CA 94143 USA. [Martins, Ana Raquel O.] Univ Coimbra, Ctr Neurosci & Cell Biol, PhD Program Expt Biol & Biomed, P-3000 Coimbra, Portugal. [Wachs, Megan; Levis, Philip A.] Stanford Univ, Dept Elect Engn, Comp Syst Lab, Palo Alto, CA 94304 USA. [Wachs, Megan; Levis, Philip A.] Stanford Univ, Dept Comp Sci, Comp Syst Lab, Palo Alto, CA 94304 USA. [Polley, Daniel B.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Eaton Peabody Lab,Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Froemke, RC (reprint author), NYU, Sch Med, Dept Physiol & Neurosci,Skirball Inst Biomol Med, Mol Neurobiol Program,Helen & Martin Kimmel Ctr B, New York, NY 10012 USA. EM robert.froemke@med.nyu.edu OI Schreiner, Christoph/0000-0002-4571-4328; Froemke, Robert/0000-0002-1230-6811; Polley, Daniel/0000-0002-5120-2409 FU US National Institute on Deafness and Other Communication Disorders [DC009635, DC009836, DC02260]; US National Science Foundation [0615308, 0627126]; Intel Research; DoCoMo Capital; Conte Center for Neuroscience Research at the University of California, San Francisco [MH077970]; Hearing Research Inc.; John C. and Edward Coleman Fund; US National Academies Keck Future Initiatives; US National Science Foundation Predoctoral Fellowship; Sequoia Capital Stanford Graduate Fellowship; US National Institute of Mental Health training grant; Microsoft Research New Faculty Fellowship; Sloan Research Fellowship; Foundation Capital FX We thank L. F. Abbott, T. Babcock, M. Berry, E. Chang, Z. Chen, E. de Villers-Sidani, A. L. Dorrn, P. Dutta, A. Fairhall, S. P. Gandhi, G. Glassner, C. A. Hoeffer, K. Imaizumi, B.J. Jones, N. Kopell, R. Liu, G. Myers, P. O'Hara, J. Shih, A.Y. Tan, C.-L. Teng and L. Wilbrecht for comments, discussions and technical assistance. J. Pivkova created the artwork in Figure 1a. This work was supported by the US National Institute on Deafness and Other Communication Disorders (grant DC009635 to R. C. F., grant DC009836 to D. B. P. and grant DC02260 to C. E. S.), US National Science Foundation (grants 0615308 and 0627126 to P. A. L.), Intel Research (P. A. L.), DoCoMo Capital and Foundation Capital (P. A. L.), the Conte Center for Neuroscience Research at the University of California, San Francisco (grant MH077970 to M. M. M. and C. E. S.), Hearing Research Inc. (C. E. S.), the John C. and Edward Coleman Fund (M. M. M. and C. E. S.) and the US National Academies Keck Future Initiatives (R. C. F. and P. A. L.). A. J. B. is supported by a US National Science Foundation Predoctoral Fellowship. M. W. is supported by a Sequoia Capital Stanford Graduate Fellowship. I. C. is supported by an US National Institute of Mental Health training grant. P. A. L. is supported by a Microsoft Research New Faculty Fellowship. R. C. F. is supported by a Sloan Research Fellowship. NR 50 TC 61 Z9 62 U1 1 U2 39 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JAN PY 2013 VL 16 IS 1 BP 79 EP U120 DI 10.1038/nn.3274 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 058KZ UT WOS:000312633900016 PM 23178974 ER PT J AU Tanaka, S Louis, DN Curry, WT Batchelor, TT Dietrich, J AF Tanaka, Shota Louis, David N. Curry, William T. Batchelor, Tracy T. Dietrich, Jorg TI Diagnostic and therapeutic avenues for glioblastoma: no longer a dead end? SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Review ID PHASE-II TRIAL; GROWTH-FACTOR RECEPTOR; HIGH-GRADE GLIOMA; RECURRENT MALIGNANT GLIOMA; MGMT PROMOTER METHYLATION; BRAIN-TUMOR CONSORTIUM; BEVACIZUMAB PLUS IRINOTECAN; INTEGRATED GENOMIC ANALYSIS; ISOCITRATE DEHYDROGENASE 1; PROGRESSION-FREE SURVIVAL AB Glioblastomas are heterogeneous neoplasms that are driven by complex signalling pathways, and are among the most aggressive and challenging cancers to treat. Despite standard treatment with resection, radiation and chemotherapy, the prognosis of patients with glioblastomas remains poor. An increasing understanding of the molecular pathogenesis of glioblastomas has stimulated the development of novel therapies, including the use of molecular-targeted agents. Identification and validation of diagnostic, prognostic and predictive biomarkers has led to the advancement of clinical trial design, and identification of glioblastoma subgroups with a more-favourable prognosis and response to therapy. In this Review, we discuss common molecular alterations relevant to the biology of glioblastomas, targeted, antiangiogenic and immunotherapies that have impacted on the treatment of this disease, and the challenges and pitfalls associated with these therapies. In addition, we emphasize current biomarkers relevant to the management of patients with glioblastoma. Tanaka, S. et al. Nat. Rev. Clin. Oncol. 10, 14-26 (2013); published online 27 November 2012; doi:10.1038/nrclinonc.2012.204 C1 [Tanaka, Shota; Batchelor, Tracy T.; Dietrich, Jorg] Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. [Louis, David N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Curry, William T.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Dietrich, J (reprint author), Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. EM dietrich.jorg@mgh.harvard.edu RI Waha, Andreas/J-2950-2014 FU National Institute of Health [K24-CA125440, R01-CA129371, R01-CA117079-02, R01-CA57683]; American Academy of Neurology Foundation; Stephen E. & Catherine Pappas Cancer Research Foundation FX The authors gratefully acknowledge the support of the National Institute of Health (K24-CA125440, R01-CA129371, R01-CA117079-02, R01-CA57683), the American Academy of Neurology Foundation (J. Dietrich), the Stephen E. & Catherine Pappas Cancer Research Foundation (J. Dietrich), and gifts from the Montesi Family Research Fund and the Simches Fund for Brain Tumor Research. J. Dietrich is a fellow of the Clinical Investigator Training Program at Beth Israel Deaconess Medical Center, Harvard Medical School. NR 148 TC 113 Z9 113 U1 9 U2 86 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD JAN PY 2013 VL 10 IS 1 BP 14 EP 26 DI 10.1038/nrclinonc.2012.204 PG 13 WC Oncology SC Oncology GA 058PR UT WOS:000312646500006 PM 23183634 ER PT J AU Lambin, P van Stiphout, RGPM Starmans, MHW Rios-Velazquez, E Nalbantov, G Aerts, HJWL Roelofs, E van Elmpt, W Boutros, PC Granone, P Valentini, V Begg, AC De Ruysscher, D Dekker, A AF Lambin, Philippe van Stiphout, Ruud G. P. M. Starmans, Maud H. W. Rios-Velazquez, Emmanuel Nalbantov, Georgi Aerts, Hugo J. W. L. Roelofs, Erik van Elmpt, Wouter Boutros, Paul C. Granone, Pierluigi Valentini, Vincenzo Begg, Adrian C. De Ruysscher, Dirk Dekker, Andre TI Predicting outcomes in radiation oncology-multifactorial decision support systems SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Review ID CELL LUNG-CANCER; COMPLICATION PROBABILITY-MODELS; SINGLE NUCLEOTIDE POLYMORPHISMS; POSITRON-EMISSION-TOMOGRAPHY; IMAGE-GUIDED RADIOTHERAPY; GENE-EXPRESSION PROGRAMS; GENOME-WIDE ASSOCIATION; DOUBLE-STRAND BREAKS; TUMOR VOLUME; NECK-CANCER AB With the emergence of individualized medicine and the increasing amount and complexity of available medical data, a growing need exists for the development of clinical decision-support systems based on prediction models of treatment outcome. In radiation oncology, these models combine both predictive and prognostic data factors from clinical, imaging, molecular and other sources to achieve the highest accuracy to predict tumour response and follow-up event rates. In this Review, we provide an overview of the factors that are correlated with outcome-including survival, recurrence patterns and toxicity-in radiation oncology and discuss the methodology behind the development of prediction models, which is a multistage process. Even after initial development and clinical introduction, a truly useful predictive model will be continuously re-evaluated on different patient datasets from different regions to ensure its population-specific strength. In the future, validated decision-support systems will be fully integrated in the clinic, with data and knowledge being shared in a standardized, instant and global manner. Lambin, P. et al. Nat. Rev. Clin. Oncol. 10, 27-40 (2013); published online 20 November 2012; doi:10.1038/nrclinonc.2012.196 C1 [Lambin, Philippe; van Stiphout, Ruud G. P. M.; Starmans, Maud H. W.; Rios-Velazquez, Emmanuel; Nalbantov, Georgi; Roelofs, Erik; van Elmpt, Wouter; De Ruysscher, Dirk; Dekker, Andre] Maastricht Univ Med Ctr, Dept Radiat Oncol MAASTRO, GROW Sch Oncol & Dev Biol, NL-6229 ET Maastricht, Netherlands. [Aerts, Hugo J. W. L.] Harvard Univ, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. [Aerts, Hugo J. W. L.] Harvard Univ, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Boutros, Paul C.] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada. [Granone, Pierluigi] Univ Cattolica Sacro Cuore, Policlin Univ Agostino Gemelli, Dept Surg, I-00168 Rome, Italy. [Valentini, Vincenzo] Univ Cattolica Sacro Cuore, Policlin Univ Agostino Gemelli, Dept Radiotherapy, I-00168 Rome, Italy. [Begg, Adrian C.] Netherlands Canc Inst, Div Biol Stress Response, NL-1066 CX Amsterdam, Netherlands. RP Lambin, P (reprint author), Maastricht Univ Med Ctr, Dept Radiat Oncol MAASTRO, GROW Sch Oncol & Dev Biol, NL-6229 ET Maastricht, Netherlands. EM philippe.lambin@maastro.nl RI Aerts, Hugo/P-6350-2015; OI Aerts, Hugo/0000-0002-2122-2003; Roelofs, Erik/0000-0003-2172-8669; Dekker, Andre/0000-0002-0422-7996; Boutros, Paul/0000-0003-0553-7520; Cuniberti, Gianaurelio/0000-0002-6574-7848 FU Center for Translational Molecular Medicine framework (AIR FORCE); European Union; QuIC-ConCePT; Innovative Medicine Initiative Joint Undertaking; Dutch Cancer Society [KWF UM 2011-5020, KWF UM 2009-4454] FX We acknowledge financial support from the Center for Translational Molecular Medicine framework (AIR FORCE), European Union sixth and seventh framework programme (ARTFORCE and METOXIA), INTERREG (www.eurocat.info), QuIC-ConCePT (funded by the Innovative Medicine Initiative Joint Undertaking) and the Dutch Cancer Society (KWF UM 2011-5020 and KWF UM 2009-4454). NR 219 TC 109 Z9 109 U1 8 U2 46 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD JAN PY 2013 VL 10 IS 1 BP 27 EP 40 DI 10.1038/nrclinonc.2012.196 PG 14 WC Oncology SC Oncology GA 058PR UT WOS:000312646500007 PM 23165123 ER PT J AU Joung, JK Sander, JD AF Joung, J. Keith Sander, Jeffry D. TI INNOVATION TALENs: a widely applicable technology for targeted genome editing SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Article ID ZINC-FINGER NUCLEASES; PLURIPOTENT STEM-CELLS; DOUBLE-STRAND BREAKS; EFFECTOR NUCLEASES; GENE DISRUPTION; DNA RECOGNITION; EMBRYO MICROINJECTION; TRANSCRIPTION FACTORS; EFFICIENT GENERATION; CLEAVAGE DOMAIN AB Engineered nucleases enable the targeted alteration of nearly any gene in a wide range of cell types and organisms. The newly-developed transcription activator-like effector nucleases (TALENs) comprise a nonspecific DNA-cleaving nuclease fused to a DNA-binding domain that can be easily engineered so that TALENs can target essentially any sequence. The capability to quickly and efficiently alter genes using TALENs promises to have profound impacts on biological research and to yield potential therapeutic strategies for genetic diseases. C1 [Joung, J. Keith; Sander, Jeffry D.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Mol Pathol Unit, Charlestown, MA 02129 USA. [Joung, J. Keith; Sander, Jeffry D.] Harvard Univ, Sch Med, Ctr Canc Res, Dept Pathol, Charlestown, MA 02129 USA. RP Joung, JK (reprint author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Mol Pathol Unit, 149 13th St,6th Floor, Charlestown, MA 02129 USA. EM jjoung@partners.org FU US National Institutes of Health (NIH) [DP1 GM105378, R01 GM088040, P50 HG005550]; Jim and Ann Orr Massachusetts General Hospital Research Scholar Award; NIH [T32CA009216] FX J.K.J. acknowledges support from the US National Institutes of Health (NIH) (grants DP1 GM105378, R01 GM088040 and P50 HG005550) and The Jim and Ann Orr Massachusetts General Hospital Research Scholar Award. J.D.S. was supported by the NIH grant T32CA009216. The authors apologize to colleagues whose studies were not cited due to length constraints. NR 100 TC 450 Z9 476 U1 24 U2 281 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 EI 1471-0080 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD JAN PY 2013 VL 14 IS 1 BP 49 EP 55 DI 10.1038/nrm3486 PG 7 WC Cell Biology SC Cell Biology GA 058QX UT WOS:000312649800014 PM 23169466 ER PT J AU Yeh, H Markmann, JF AF Yeh, Heidi Markmann, James F. TI TRANSPLANTATION Are calcineurin inhibitors safer than mTOR inhibitors? SO NATURE REVIEWS NEPHROLOGY LA English DT News Item ID RENAL-FAILURE; LIFE-SPAN; SIROLIMUS; RAPAMYCIN; RECIPIENTS; RECOVERY AB Isakova et al. report that kidney transplant recipients on mammalian target of rapamycin (mTOR) inhibitors do not have a lower risk of allograft failure but do have a higher risk of death than those on calcineurin inhibitors. Careful consideration is, therefore, required before converting to mTOR inhibitors to preserve renal function. Yeh, H. & Markmann, J. F. Nat. Rev. Nephrol. 9, 11-13 (2013); published online 27 November 2012; doi:10.1038/nrneph.2012.262 C1 [Yeh, Heidi; Markmann, James F.] Massachusetts Gen Hosp, Div Transplant Surg, Boston, MA 02114 USA. RP Markmann, JF (reprint author), Massachusetts Gen Hosp, Div Transplant Surg, 55 Fruit St,White 517, Boston, MA 02114 USA. EM jmarkmann@partners.org FU NIAID NIH HHS [R01 AI057851] NR 10 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 1759-5061 J9 NAT REV NEPHROL JI Nat. Rev. Nephrol. PD JAN PY 2013 VL 9 IS 1 BP 11 EP 13 DI 10.1038/nrneph.2012.262 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 057WW UT WOS:000312596000005 PM 23183834 ER PT J AU van der Laan, AM Nahrendorf, M Piek, JJ AF van der Laan, Anja M. Nahrendorf, Matthias Piek, Jan J. TI Healing and adverse remodelling after acute myocardial infarction: role of the cellular immune response SO POSTGRADUATE MEDICAL JOURNAL LA English DT Article ID PERIPHERAL-BLOOD; MONOCYTE SUBSETS; STEM-CELLS; INFLAMMATION; ANGIOPLASTY; INTRACORONARY; RECEPTOR; INJURY C1 [van der Laan, Anja M.; Piek, Jan J.] Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1100 DD Amsterdam, Netherlands. [Nahrendorf, Matthias] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA. RP Piek, JJ (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Cardiol, POB 22660, NL-1100 DD Amsterdam, Netherlands. EM j.j.piek@amc.uva.nl FU Graduate School for Medical Sciences of the Academic Medical Centre, Amsterdam, The Netherlands; National Institutes of Health [R01HL096576] FX This work was supported by a grant by the Graduate School for Medical Sciences of the Academic Medical Centre, Amsterdam, The Netherlands to AML, and a grant from the National Institutes of Health (R01HL096576) to MN. NR 20 TC 2 Z9 2 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0032-5473 J9 POSTGRAD MED J JI Postgrad. Med. J. PD JAN PY 2013 VL 89 IS 1047 BP 52 EP 58 DI 10.1136/postgradmedj-2012-301623rep PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 057KI UT WOS:000312561700010 PM 23257717 ER PT J AU Dzik, W AF Dzik, Walter Sunny TI In Appreciation of Dr Morris A. Blajchman, Founding Editor of Transfusion Medicine Reviews SO TRANSFUSION MEDICINE REVIEWS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02446 USA. RP Massachusetts Gen Hosp, Room J-224,55 Fruit St, Boston, MA 02446 USA. EM sdzik@partners.org NR 0 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 0887-7963 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD JAN PY 2013 VL 27 IS 1 BP 1 EP 1 DI 10.1016/j.tmrv.2012.06.001 PG 1 WC Hematology SC Hematology GA 055QM UT WOS:000312431500001 ER PT J AU Winthrop, KL Baxter, R Liu, L Varley, CD Curtis, JR Baddley, JW McFarland, B Austin, D Radcliffe, L Suhler, EB Choi, D Rosenbaum, JT Herrinton, LJ AF Winthrop, K. L. Baxter, R. Liu, L. Varley, C. D. Curtis, J. R. Baddley, J. W. McFarland, B. Austin, D. Radcliffe, L. Suhler, E. B. Choi, D. Rosenbaum, J. T. Herrinton, L. J. TI Mycobacterial diseases and antitumour necrosis factor therapy in USA SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID NONTUBERCULOUS MYCOBACTERIA; RHEUMATOID-ARTHRITIS; TUBERCULOSIS INFECTION; FACTOR ANTAGONISTS; LUNG-DISEASE; RISK; PREVALENCE; RECOMMENDATIONS; EPIDEMIOLOGY; ETANERCEPT AB Objective In North America, tuberculosis and nontuberculous mycobacterial (NTM) disease rates associated with antitumour necrosis factor a (anti-TNF alpha) therapy are unknown. Methods At Kaiser Permanente Northern California, the authors searched automated pharmacy records to identify inflammatory disease patients who received anti-TNF therapy during 2000-2008 and used validated electronic search algorithms to identify NTM and tuberculosis cases occurring during anti-TNF drug exposure. Results Of 8418 anti-TNF users identified, 60% had rheumatoid arthritis (RA). Among anti-TNF users, 18 developed NTM and 16 tuberculosis after drug start. Anti-TNF associated rates of NTM and tuberculosis were 74 (95% CI: 37 to 111) and 49 (95% CI: 18 to 79) per 100 000 person-years, respectively. Rates (per 100,000 person-years) for NTM and tuberculosis respectively for etanercept were 35 (95% CI: 1 to 69) and 17 (95% CI: 0 to 41); infliximab, 116 (95% CI: 30 to 203) and 83 (95% CI: 10 to 156); and adalimumab, 122 (95% CI: 3 to 241) and 91 (95% CI: 19 to 267). Background rates for NTM and tuberculosis in unexposed RA-patients were 19.2 (14.2 to 25.0) and 8.7 (5.3 to 13.2), and in the general population were 4.1 (95% CI 3.9 to 4.4) and 2.8 (95% CI 2.6 to 3.0) per 100,000 person-years. Among anti-TNF users, compared with uninfected individuals, NTM case-patients were older (median age 68 vs 50 years, p < 0.01) and more likely to have RA (100% vs 60%, p < 0.01); whereas, tuberculosis case-patients were more likely to have diabetes (37% vs 16%, p=0.02) or chronic renal disease (25% vs 6%, p=0.02). Conclusions Among anti-TNF users in USA, mycobacterial disease rates are elevated, and NTM is associated with RA. C1 [Winthrop, K. L.] Oregon Hlth & Sci Univ, Dept Infect Dis, Portland, OR 97201 USA. [Winthrop, K. L.; Austin, D.; Choi, D.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Winthrop, K. L.; Varley, C. D.; Suhler, E. B.; Rosenbaum, J. T.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. [Rosenbaum, J. T.] Oregon Hlth & Sci Univ, Dept Rheumatol, Portland, OR 97201 USA. [Baxter, R.] Kaiser Permanente No Calif, Dept Infect Dis, Oakland, CA USA. [Liu, L.; Herrinton, L. J.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Austin, D.; Radcliffe, L.; Suhler, E. B.] Portland VA Med Ctr, Portland, OR USA. [Baddley, J. W.] Univ Alabama Birmingham, Dept Infect Dis, Birmingham, AL USA. [Curtis, J. R.] Univ Alabama Birmingham, Dept Rheumatol, Birmingham, AL USA. RP Winthrop, KL (reprint author), Oregon Hlth & Sci Univ, 3375 SW Terwilliger Dr, Portland, OR 97239 USA. EM winthrop@ohsu.edu OI McFarland, Bentson/0000-0001-9149-5616 FU UCB pharmaceuticals; Agency for Healthcare Research and Quality (AHRQ) [1K08HS017552-01]; Amgen; Genentech; Oxford Immunotech; Centocor; CORRONA; Abbott FX This work was funded by a grant from UCB pharmaceuticals. KL Winthrop's work on this manuscript was funded by an Agency for Healthcare Research and Quality (AHRQ) grant (1K08HS017552-01).; KL Winthrop has received a grant from UCB pharmaceuticals and scientific advisory board fees from Amgen, Genentech, and Oxford Immunotech. JR Curtis has served as a consultant for Roche/Genentech, UCB, Centocor, CORRONA, Amgen, Pfizer, BMS, Crescendo and Abbott, and has received research support from Amgen, Roche/Genentech, Centocor and CORRONA. JW Baddley has served as a consultant for Abbott. EB Suhler has received research support from Abbott and Centocor. JT Rosenbaum consults for Amgen, Abbott, Centocor, and Genentech and has received grant support from Centocor, Genentech, and Abbott. LJ Herrinton has a research contract with Genentech and Proctor and Gamble NR 29 TC 64 Z9 65 U1 0 U2 4 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JAN PY 2013 VL 72 IS 1 BP 37 EP 42 DI 10.1136/annrheumdis-2011-200690 PG 6 WC Rheumatology SC Rheumatology GA 055IB UT WOS:000312407800007 PM 22523429 ER PT J AU Porter, SA Pedley, A Massaro, JM Vasan, RS Hoffmann, U Fox, CS AF Porter, Stacy A. Pedley, Alison Massaro, Joseph M. Vasan, Ramachandran S. Hoffmann, Udo Fox, Caroline S. TI Aminotransferase Levels Are Associated With Cardiometabolic Risk Above and Beyond Visceral Fat and Insulin Resistance The Framingham Heart Study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE cardiometabolic risk factors; insulin resistance; liver function tests; obesity; visceral fat ID SERUM ALANINE AMINOTRANSFERASE; LIVER-DISEASE; METABOLIC SYNDROME; NONALCOHOLIC STEATOHEPATITIS; TRANSAMINASE-ACTIVITY; ADIPONECTIN; DYSLIPIDEMIA; PREVALENCE; SPECTRUM; GLUCOSE AB Objective-We sought to characterize associations between aminotransferase levels and cardiometabolic risk after accounting for visceral adipose tissue and insulin resistance. Methods and Results-Participants (n=2621) from the Framingham Heart Study (mean age 51, 49.8% women) were included. Sex-specific linear and logistic regressions were used to evaluate associations between aminotransferase levels and cardiometabolic risk factors. In multivariable models, increased alanine aminotransferase levels were associated with elevated blood pressure, fasting plasma glucose, and triglycerides and lower high-density lipoprotein levels (all P <= 0.007). Furthermore, each 1-SD increase in alanine aminotransferase corresponded to an increased odds of hypertension, diabetes mellitus, the metabolic syndrome, impaired fasting glucose, and insulin resistance estimated by the homeostasis model assessment of insulin resistance (odds ratio, 1.29-1.85, all P <= 0.002). Associations with alanine aminotransferase persisted after additional adjustment for visceral adipose tissue, insulin resistance, and body mass index with the exception of high-density lipoprotein cholesterol in both sexes and blood pressure in women. Results were materially unchanged when moderate drinkers were excluded, when the sample was restricted to those with alanine aminotransferase <40 U/L, and when the sample was restricted to those without diabetes mellitus. Similar trends were observed for aspartate aminotransferase levels, but associations were more modest. Conclusion-Aminotransferase levels are correlated with multiple cardiometabolic risk factors above and beyond visceral adipose tissue and insulin resistance. (Arterioscler Thromb Vasc Biol. 2013;33:139-146.) C1 [Massaro, Joseph M.; Vasan, Ramachandran S.; Fox, Caroline S.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Porter, Stacy A.; Pedley, Alison; Fox, Caroline S.] NHLBI, Ctr Populat Studies, Framingham, MA USA. [Porter, Stacy A.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. [Hoffmann, Udo; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Hypertens & Metab, Boston, MA 02115 USA. RP Fox, CS (reprint author), 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@Nhlbi.nih.gov OI Massaro, Joseph/0000-0002-2682-4812; Ramachandran, Vasan/0000-0001-7357-5970 FU Boston University School of Medicine; National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195] FX This work was supported by the Boston University School of Medicine and the National Heart, Lung, and Blood Institute's Framingham Heart Study (contract N01-HC-25195). NR 37 TC 14 Z9 15 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JAN PY 2013 VL 33 IS 1 BP 139 EP + DI 10.1161/ATVBAHA.112.300075 PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 055CJ UT WOS:000312392500021 PM 23162012 ER PT J AU Burdett, TC Desjardins, CA Logan, R McFarland, NR Chen, XQ Schwarzschild, MA AF Burdett, Thomas C. Desjardins, Cody A. Logan, Robert McFarland, Nikolaus R. Chen, Xiqun Schwarzschild, Michael A. TI Efficient determination of purine metabolites in brain tissue and serum by high-performance liquid chromatography with electrochemical and UV detection SO BIOMEDICAL CHROMATOGRAPHY LA English DT Article DE HPLC; electrochemical detection; UV-vis detection; biological specimens; purines ID CENTRAL-NERVOUS-SYSTEM; URIC-ACID; PARKINSONS-DISEASE; COLUMN CHROMATOGRAPHY; OXIDATIVE STRESS; IN-VIVO; BASES; HYPOXANTHINE; NUCLEOTIDES; NUCLEOSIDES AB The purine metabolic pathway has been implicated in neurodegeneration and neuroprotection. High-performance liquid chromatography (HPLC) is widely used to determine purines and metabolites. However, methods for analysis of multiple purines in a single analysis have not been standardized, especially in brain tissue. We report the development and validation of a reversed-phase HPLC method combining electrochemical and UV detection after a short gradient run to measure seven purine metabolites (adenosine, guanosine, inosine, guanine, hypoxanthine, xanthine and urate) from the entire purine metabolic pathway. The limit of detection (LoD) for each analyte was determined. The LoD using UV absorption was 0.001 mg/dL for hypoxanthine (Hyp), inosine (Ino), guanosine (Guo) and adenosine (Ado), and those using coulometric electrodes were 0.001 mg/dL for guanine (Gua), 0.0001 mg/dL for urate (UA) and 0.0005 mg/dL for xanthine (Xan). The intra- and inter-day coefficient of variance was generally <8%. Using this method, we determined basal levels of these metabolites in mouse brain and serum, as well as in post-mortem human brain. Peak identities were confirmed by enzyme degradation. Spike recovery was performed to assess accuracy. All recoveries fell within 80120%. Our HPLC method provides a sensitive, rapid, reproducible and low-cost method for determining multiple purine metabolites in a single analysis in serum and brain specimens. Copyright (c) 2012 John Wiley & Sons, Ltd. C1 [Burdett, Thomas C.; Desjardins, Cody A.; Logan, Robert; Chen, Xiqun; Schwarzschild, Michael A.] Harvard Univ, Sch Med 114 16, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis,Dept Neurol, Charlestown, MA 02129 USA. [McFarland, Nikolaus R.] Univ Florida, Dept Neurol, Ctr Translat Res Neurodegenerat Dis, Gainesville, FL 32610 USA. RP Chen, XQ (reprint author), Harvard Univ, Sch Med 114 16, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis,Dept Neurol, Charlestown, MA 02129 USA. EM xchen17@partners.org OI McFarland, Nikolaus/0000-0002-8699-8857 FU RJG Foundation; Michael J. Fox Foundation; American Federation for Aging Research; NIH [R21NS058324, K24NS060991]; US Department of Defense [W81XWH-11-1-0150] FX The authors would like to acknowledge Yuehang Xu for her excellent technical support. This work is supported by the RJG Foundation, Michael J. Fox Foundation, American Federation for Aging Research, NIH grants R21NS058324 and K24NS060991, and US Department of Defense W81XWH-11-1-0150. NR 24 TC 6 Z9 7 U1 1 U2 40 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-3879 J9 BIOMED CHROMATOGR JI Biomed. Chromatogr. PD JAN PY 2013 VL 27 IS 1 BP 122 EP 129 DI 10.1002/bmc.2760 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy GA 053WP UT WOS:000312306300016 PM 22674671 ER PT J AU Le, U Melancon, BJ Bridges, TM Vinson, PN Utley, TJ Lamsal, A Rodriguez, AL Venable, D Sheffler, DJ Jones, CK Blobaum, AL Wood, MR Daniels, JS Conn, PJ Niswender, CM Lindsley, CW Hopkins, CR AF Le, Uyen Melancon, Bruce J. Bridges, Thomas M. Vinson, Paige N. Utley, Thomas J. Lamsal, Atin Rodriguez, Alice L. Venable, Daryl Sheffler, Douglas J. Jones, Carrie K. Blobaum, Anna L. Wood, Michael R. Daniels, J. Scott Conn, P. Jeffrey Niswender, Colleen M. Lindsley, Craig W. Hopkins, Corey R. TI Discovery of a selective M-4 positive allosteric modulator based on the 3-amino-thieno[2,3-b]pyridine-2-carboxamide scaffold: Development of ML253, a potent and brain penetrant compound that is active in a preclinical model of schizophrenia SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Muscarinic receptor 4; Positive allosteric modulator; Amphetamine induced hyperlocomotion; CNS; PAM ID MUSCARINIC ACETYLCHOLINE-RECEPTOR; KNOCKOUT MICE; BINDING AB Herein we report a next generation muscarinic receptor 4 (M-4) positive allosteric modulator (PAM), ML253 which exhibits nanomolar activity at both the human (EC50 = 56 nM) and rat (EC50 = 176 nM) receptors and excellent efficacy by the left-ward shift of the ACh concentration response curve (fold shift, human = 106; rat = 50). In addition, ML253 is selective against the four other muscarinic subtypes, displays excellent CNS exposure and is active in an amphetamine-induced hyperlocomotion assay. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Le, Uyen; Melancon, Bruce J.; Bridges, Thomas M.; Vinson, Paige N.; Utley, Thomas J.; Lamsal, Atin; Rodriguez, Alice L.; Venable, Daryl; Sheffler, Douglas J.; Jones, Carrie K.; Blobaum, Anna L.; Wood, Michael R.; Daniels, J. Scott; Conn, P. Jeffrey; Niswender, Colleen M.; Lindsley, Craig W.; Hopkins, Corey R.] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. [Wood, Michael R.; Lindsley, Craig W.; Hopkins, Corey R.] Vanderbilt Univ, Dept Chem, Nashville, TN 37232 USA. [Le, Uyen; Melancon, Bruce J.; Bridges, Thomas M.; Vinson, Paige N.; Utley, Thomas J.; Lamsal, Atin; Rodriguez, Alice L.; Venable, Daryl; Sheffler, Douglas J.; Jones, Carrie K.; Blobaum, Anna L.; Wood, Michael R.; Daniels, J. Scott; Conn, P. Jeffrey; Niswender, Colleen M.; Lindsley, Craig W.; Hopkins, Corey R.] Vanderbilt Univ, Med Ctr, Vanderbilt Ctr Neurosci Drug Discovery, Nashville, TN 37232 USA. [Le, Uyen; Melancon, Bruce J.; Bridges, Thomas M.; Vinson, Paige N.; Utley, Thomas J.; Lamsal, Atin; Rodriguez, Alice L.; Venable, Daryl; Sheffler, Douglas J.; Jones, Carrie K.; Blobaum, Anna L.; Wood, Michael R.; Daniels, J. Scott; Conn, P. Jeffrey; Niswender, Colleen M.; Lindsley, Craig W.; Hopkins, Corey R.] Vanderbilt Specialized Chem Ctr Probe Dev MLPCN, Nashville, TN 37232 USA. [Jones, Carrie K.] US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville, TN 37232 USA. RP Hopkins, CR (reprint author), Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. EM corey.r.hopkins@vanderbilt.edu FU Vanderbilt Specialized Chemistry Center for Accelerated Probe Development [U54MH04659] FX The authors would like to thank Tammy Santomango and Frank Byers for technical assistance with the PK experiments and Nathan Kett and Sichen Chang for purification of the compounds. Vanderbilt is a member of the MLPCN and houses the Vanderbilt Specialized Chemistry Center for Accelerated Probe Development (U54MH04659). NR 15 TC 14 Z9 14 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JAN 1 PY 2013 VL 23 IS 1 BP 346 EP 350 DI 10.1016/j.bmcl.2012.10.073 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 053JO UT WOS:000312267700064 PM 23177787 ER PT J AU Tindell, K Garfinkel, R Abu-Haydar, E Ahn, R Burke, TF Conn, K Eckardt, M AF Tindell, K. Garfinkel, R. Abu-Haydar, E. Ahn, R. Burke, T. F. Conn, K. Eckardt, M. TI Uterine balloon tamponade for the treatment of postpartum haemorrhage in resource-poor settings: a systematic review SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Review DE Maternal mortality; postpartum haemorrhage; resource-poor settings; treatment; uterine balloon tamponade ID ANTI-SHOCK GARMENT; MANAGEMENT; STANDARDS; COUNTRIES; CARE AB Background Effective interventions addressing postpartum haemorrhage (PPH) are critically needed to reduce maternal mortality worldwide. Uterine balloon tamponade (UBT) has been shown to be an effective technique to treat PPH in developed countries, but has not been examined in resource-poor settings. Objectives This literature review examines the effectiveness of UBT for the treatment and management of PPH in resource-poor settings. Search strategy Publications were sought through searches of five electronic databases: Medline, Cochrane Reference Libraries, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Embase and Popline. Selection criteria Titles and abstracts were screened for eligibility by two independent reviewers. Each reviewer evaluated the full text of potentially eligible articles by defined inclusion criteria, including the presentation of empirical data and use of UBT in resource-poor settings to treat PPH. Data collection and analysis Full text of all eligible publications was collected and systematically coded. Main results The search identified 13 studies that met the inclusion criteria: six case reports or case series, five prospective studies and two retrospective studies for a total of 241 women. No randomised controlled trials were identified. The studies used various types of UBT, including condom catheter (n = 193), Foley catheter (n = 5) and SengstakenBlakemore oesophageal tube (n = 1). In these studies, primarily conducted in tertiary-care settings rather than lower-level health facilities, UBT successfully treated PPH in 234 out of 241 women. Conclusions UBT is an effective treatment for PPH in resource-poor settings. Further study of UBT interventions is necessary to better understand the barriers to successful implementation and use in these settings. C1 [Tindell, K.; Ahn, R.; Burke, T. F.; Conn, K.; Eckardt, M.] Massachusetts Gen Hosp, Div Global Hlth & Human Rights, Dept Emergency Med, Boston, MA 02114 USA. [Tindell, K.; Ahn, R.; Burke, T. F.] Harvard Univ, Sch Med, Boston, MA USA. [Garfinkel, R.; Abu-Haydar, E.] PATH, Seattle, WA USA. [Garfinkel, R.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Burke, T. F.] Childrens Hosp, Div Pediat, Boston, MA 02115 USA. [Eckardt, M.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Tindell, K (reprint author), Massachusetts Gen Hosp, Div Global Hlth & Human Rights, Dept Emergency Med, Zero Emerson Pl,Suite 104, Boston, MA 02114 USA. EM kathryn_tindell@hms.harvard.edu OI Eckardt, Melody/0000-0001-9066-9856 FU Ujenzi Charitable Trust, Division of Global Health & Human Rights, Department of Emergency Medicine, Massachusetts General Hospital; PATH FX Funding for this research was provided by Ujenzi Charitable Trust, Division of Global Health & Human Rights, Department of Emergency Medicine, Massachusetts General Hospital, and PATH. NR 34 TC 16 Z9 19 U1 2 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1470-0328 EI 1471-0528 J9 BJOG-INT J OBSTET GY JI BJOG PD JAN PY 2013 VL 120 IS 1 BP 5 EP 14 DI 10.1111/j.1471-0528.2012.03454.x PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 053VX UT WOS:000312304300003 PM 22882240 ER PT J AU Mehrotra, M Williams, CR Ogawa, M LaRue, AC AF Mehrotra, Meenal Williams, Christopher R. Ogawa, Makio LaRue, Amanda C. TI Hematopoietic stem cells give rise to osteo-chondrogenic cells SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE Hematopoietic stem cell; Fracture; Transplant; Fracture repair ID MARROW STROMAL CELLS; LONG-BONE REPAIR; IN-VIVO; PROGENITOR CELLS; SKELETAL-MUSCLE; LINEAGE CELLS; FRACTURE; ORIGIN; TRANSPLANTATION; DEFECTS AB Repair of bone fracture requires recruitment and proliferation of stem cells with the capacity to differentiate to functional osteoblasts. Given the close association of bone and bone marrow (BM), it has been suggested that BM may serve as a source of these progenitors. To test the ability of hematopoietic stem cells (HSCs) to give rise to osteo-chondrogenic cells, we used a single HSC transplantation paradigm in uninjured bone and in conjunction with a tibial fracture model. Mice were lethally irradiated and transplanted with a clonal population of cells derived from a single enhanced green fluorescent protein positive (eGFP(+)) HSC. Analysis of paraffin sections from these animals showed the presence of eGFP(+) osteocytes and hypertrophic chondrocytes. To determine the contribution of HSC-derived cells to fracture repair, non-stabilized tibial fracture was created. Paraffin sections were examined at 7 days, 2 weeks and 2 months after fracture and eGFP(+) hypertrophic chondrocytes, osteoblasts and osteocytes were identified at the callus site. These cells stained positive for Runx-2 or osteocalcin and also stained for eGFP demonstrating their origin from the HSC. Together, these findings strongly support the concept that HSCs generate bone cells and suggest therapeutic potentials of HSCs in fracture repair. (C) 2012 Elsevier Inc. All rights reserved. C1 [Mehrotra, Meenal; Ogawa, Makio; LaRue, Amanda C.] Med Univ S Carolina, Ralph H Johnson VAMC, Dept Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Mehrotra, Meenal; Williams, Christopher R.; Ogawa, Makio; LaRue, Amanda C.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29401 USA. [Mehrotra, Meenal; Ogawa, Makio; LaRue, Amanda C.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29401 USA. RP LaRue, AC (reprint author), Med Univ S Carolina, Ralph H Johnson VAMC, Dept Vet Affairs Med Ctr, 109 Bee St, Charleston, SC 29401 USA. EM laruerc@musc.edu FU Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs (merit award); National Institutes of Health [R01 HL069123, K01 AR059097-01]; Flow Cytometry and Cell Sorting Shared Resource; Cancer Center [P30 CA138313]; Small Animal Imaging Shared Resource of the Hollings Cancer Center at the Medical University of South Carolina FX This work is supported in part by the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs (merit award, ACL). The contents of this manuscript do not represent the views of the Department of Veterans Affairs or the United States Government. This work was also supported by National Institutes of Health grants R01 HL069123 (MO) and K01 AR059097-01 (MM).; The research presented in this article was supported in part by the Flow Cytometry and Cell Sorting Shared Resource, funded by a Cancer Center Support grant P30 CA138313, and the Small Animal Imaging Shared Resource of the Hollings Cancer Center at the Medical University of South Carolina. The authors would like to specifically thank Dr. Haiqun Zeng for assistance in FACS sorting. We also thank Ms. Dayvia A. Laws and Mr. Jonathan McGuirt for assistance in transplantation experiments and tissue processing and the staff of the Radiation Oncology Department of the Medical University of South Carolina in irradiation of mice. NR 50 TC 7 Z9 7 U1 3 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD JAN PY 2013 VL 50 IS 1 BP 41 EP 49 DI 10.1016/j.bcmd.2012.08.003 PG 9 WC Hematology SC Hematology GA 052YU UT WOS:000312237400008 PM 22954476 ER PT J AU Snuderl, M Wirth, D Sheth, SA Bourne, SK Kwon, CS Ancukiewicz, M Curry, WT Frosch, MP Yaroslavsky, AN AF Snuderl, Matija Wirth, Dennis Sheth, Sameer A. Bourne, Sarah K. Kwon, Churl-Su Ancukiewicz, Marek Curry, William T. Frosch, Matthew P. Yaroslavsky, Anna N. TI Dye-Enhanced Multimodal Confocal Imaging as a Novel Approach to Intraoperative Diagnosis of Brain Tumors SO BRAIN PATHOLOGY LA English DT Article DE brain tumors; fluorescence; multimodal confocal imaging; reflectance ID NONMELANOMA SKIN CANCERS; METHYLENE-BLUE; 5-AMINOLEVULINIC ACID; MALIGNANT GLIOMA; IN-VIVO; BLADDER; MICROSCOPY; RESECTION; LOCALIZATION; RADIOTHERAPY AB Intraoperative diagnosis plays an important role in accurate sampling of brain tumors, limiting the number of biopsies required and improving the distinction between brain and tumor. The goal of this study was to evaluate dye-enhanced multimodal confocal imaging for discriminating gliomas from nonglial brain tumors and from normal brain tissue for diagnostic use. We investigated a total of 37 samples including glioma (13), meningioma (7), metastatic tumors (9) and normal brain removed for nontumoral indications (8). Tissue was stained in 0.05?mg/mL aqueous solution of methylene blue (MB) for 25 minutes and multimodal confocal images were acquired using a custom-built microscope. After imaging, tissue was formalin fixed and paraffin embedded for standard neuropathologic evaluation. Thirteen pathologists provided diagnoses based on the multimodal confocal images. The investigated tumor types exhibited distinctive and complimentary characteristics in both the reflectance and fluorescence responses. Images showed distinct morphological features similar to standard histology. Pathologists were able to distinguish gliomas from normal brain tissue and nonglial brain tumors, and to render diagnoses from the images in a manner comparable to haematoxylin and eosin (H&E) slides. These results confirm the feasibility of multimodal confocal imaging for intravital intraoperative diagnosis. C1 [Wirth, Dennis; Yaroslavsky, Anna N.] Univ Massachusetts, Dept Phys & Appl Phys, Adv Biophoton Lab, Lowell, MA 01854 USA. [Snuderl, Matija; Frosch, Matthew P.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Sheth, Sameer A.; Bourne, Sarah K.; Kwon, Churl-Su; Curry, William T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. [Ancukiewicz, Marek] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Yaroslavsky, Anna N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Yaroslavsky, AN (reprint author), Univ Massachusetts, Dept Phys & Appl Phys, Adv Biophoton Lab, Suites 110-111,175 Cabot St, Lowell, MA 01854 USA. EM yaroslav@helix.mgh.harvard.edu OI Snuderl, Matija/0000-0003-0752-0917 FU MGH Cancer Center grant; UMASS Lowell seed grant FX Grant support: MGH Cancer Center grant and UMASS Lowell seed grant. NR 33 TC 12 Z9 12 U1 0 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD JAN PY 2013 VL 23 IS 1 BP 73 EP 81 DI 10.1111/j.1750-3639.2012.00626.x PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 053CV UT WOS:000312248600009 PM 22882328 ER PT J AU Ackerman, KE Patel, KT Guereca, G Pierce, L Herzog, DB Misra, M AF Ackerman, Kathryn E. Patel, Kamal T. Guereca, Gabriela Pierce, Lisa Herzog, David B. Misra, Madhusmita TI Cortisol secretory parameters in young exercisers in relation to LH secretion and bone parameters SO CLINICAL ENDOCRINOLOGY LA English DT Article ID ENDOCRINE-METABOLIC ABERRATIONS; GONADOTROPIN-RELEASING-HORMONE; LUTEINIZING-HORMONE; HYPOTHALAMIC AMENORRHEA; MENSTRUAL DISTURBANCES; ANOREXIA-NERVOSA; GHRELIN; LEPTIN; WOMEN; NEUROENDOCRINE AB Objective Amenorrhoea and low bone density are common in excessive exercisers, yet endocrine factors that differentiate adolescent amenorrhoeic exercisers (AE) from eumenorrhoeic exercisers (EE) are unclear. We have previously reported that high ghrelin and low leptin predict lower LH secretion in AE. Leptin and ghrelin impact cortisol secretion, and hypercortisolaemia can inhibit LH pulsatility. We hypothesized that higher cortisol secretion in young endurance weight-bearing AE compared with EE and nonexercisers predicts lower LH secretion, lower levels of a bone formation marker and higher levels of a bone resorption marker. Design Cross-sectional. Subjects We studied 21 AE, 18 EE and 20 nonexercisers aged 1421 years (BMI 10th90th%iles). Measurements Subjects underwent frequent sampling (11 p.m. to 7 a.m.) to assess cortisol, ghrelin, leptin and LH secretory dynamics. Fasting levels of a bone formation (P1NP) and bone resorption (CTX) marker were measured. Results BMI did not differ among groups. Cortisol pulse amplitude, mass, half-life and area under the curve (AUC) were highest in AE (P = 0.04, 0.007, 0.04 and 0.003) and were associated inversely with fat mass (r = -0.29, -0.28 and -0.35, P = 0.03, 0.04 and 0.007). We observed inverse associations between cortisol and LH AUC (r = -0.36, P = 0.008), which persisted after controlling for fat mass, leptin and ghrelin AUC. Cortisol correlated positively with CTX in EE and inversely with P1NP in nonexercisers. Conclusions Higher cortisol secretion in AE compared with EE and nonexercisers is associated with lower LH secretion. Effects of leptin and ghrelin on LH secretion may be mediated by increased cortisol. C1 [Ackerman, Kathryn E.; Patel, Kamal T.; Guereca, Gabriela; Pierce, Lisa; Misra, Madhusmita] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Ackerman, Kathryn E.; Patel, Kamal T.; Guereca, Gabriela; Pierce, Lisa; Misra, Madhusmita] Harvard Univ, Sch Med, Boston, MA USA. [Ackerman, Kathryn E.] Childrens Hosp, Div Sports Med, Boston, MA 02115 USA. [Herzog, David B.] Massachusetts Gen Hosp, Harris Ctr, Boston, MA 02114 USA. [Misra, Madhusmita] Mass Gen Hosp Children, Pediat Endocrine Unit, Boston, MA USA. RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457,55 Fruit St, Boston, MA 02114 USA. EM mmisra@partners.org FU NIH [1 UL1 RR025758-01, 1 R01 HD060827-01A1] FX We would like to thank the CRC dieticians for their help analysing the food records and exercise questionnaires, and the CRC nurses for performing the frequent blood sampling required for this study. We would also like to thank our study subjects, without whom this study would not have been possible. This study was supported by NIH grants 1 UL1 RR025758-01 and 1 R01 HD060827-01A1. NR 34 TC 7 Z9 7 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-0664 EI 1365-2265 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD JAN PY 2013 VL 78 IS 1 BP 114 EP 119 DI 10.1111/j.1365-2265.2012.04458.x PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 053DF UT WOS:000312249800018 PM 22671919 ER PT J AU Souza, FF de Angelo, M O'Regan, K Jagganathan, J Krajewski, K Ramaiya, N AF Souza, Frederico F. de Angelo, Mauricio O'Regan, Kevin Jagganathan, Jyothi Krajewski, Katherine Ramaiya, Nikhil TI Malignant primary chest wall neoplasms: a pictorial review of imaging findings SO CLINICAL IMAGING LA English DT Review DE Malignant primary chest wall neoplasms; CT; MRI; PET ID PATHOLOGICAL CORRELATION; TUMORS; CHONDROSARCOMA; APPEARANCE AB Malignant primary chest wall neoplasms (MCWN) are uncommon. Although benign chest wall neoplasms are most commonly asymptomatic, MCWN typically manifest as painful, fast growing masses. While the imaging features of malignant masses can be nonspecific, knowledge of the typical radiologic manifestations of MCWN may suggest a specific diagnosis. We review imaging features of the most common MCWN with images collected at an outpatient academic oncologic center. Objective: While the imaging features of patients with malignant masses can be nonspecific, knowledge of the typical radiologic manifestations of MCWN may suggest a specific diagnosis. We review distinguishing imaging features of the most common MCWN, including epithelial and mesenchymal malignancies, with images collected at an outpatient oncologic center. Conclusion: Chest wall neoplasms encompass 5% of all thoracic tumors, with nearly half of chest wall neoplasms being malignant. Out of these malignant neoplasms, 50% are primary and the commonest one is chondrosarcoma. Although distinguishing imaging features may suggest a specific diagnosis in the majority of MCWN, most affected patients undergo biopsy for a definitive diagnosis. (C) 2013 Elsevier Inc. All rights reserved. C1 [Souza, Frederico F.; de Angelo, Mauricio] Univ Mississippi, Med Ctr, Dept Radiol, Jackson, MS 39216 USA. [O'Regan, Kevin; Jagganathan, Jyothi; Krajewski, Katherine; Ramaiya, Nikhil] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. RP Souza, FF (reprint author), Univ Mississippi, Med Ctr, Dept Radiol, Jackson, MS 39216 USA. EM fsouza@umc.edu NR 20 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-7071 J9 CLIN IMAG JI Clin. Imaging PD JAN-FEB PY 2013 VL 37 IS 1 BP 8 EP 17 DI 10.1016/j.clinimag.2012.04.005 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 053PD UT WOS:000312284100002 PM 23206603 ER PT J AU Hedgire, SS Elmi, A Nadkarni, ND Cao, K McDermott, S Harisinghani, MG AF Hedgire, Sandeep S. Elmi, Azadeh Nadkarni, Nishad D. Cao, Kai McDermott, Shaunagh Harisinghani, Mukesh G. TI Preoperative evaluation of perinephric fat invasion in patients with renal cell carcinoma: correlation with pathological findings SO CLINICAL IMAGING LA English DT Article DE Renal cell carcinoma; Perinephric fat; Preoperative imaging ID PROGNOSTIC-SIGNIFICANCE; TUMOR SIZE; CT; ABILITY; IMPACT; MRI AB The purpose of this study was to evaluate the role of computed tomography (CT) and magnetic resonance imaging (MRI) scans in predicting perinephrie fat invasion. Preoperative CT and MRI scans of 109 patients were assessed retrospectively by two radiologists focusing on perinephric fat invasion. Findings were correlated with histopathology. Perinephric fat involvement on imaging was reported in 55 cases, and postoperative pathology record confirmed it in 32 patients. The sensitivity, specificity, positive predictive value, and negative predictive value were 82%, 63%, 48%, and 89%, respectively, with a P value of .001. To conclude, cross-sectional imaging techniques can reliably predict perinephrie fat invasion in renal carcinomas preoperatively. (C) 2013 Elsevier Inc. All rights reserved. C1 [Hedgire, Sandeep S.; Elmi, Azadeh; Nadkarni, Nishad D.; Cao, Kai; McDermott, Shaunagh; Harisinghani, Mukesh G.] Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Hedgire, SS (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM Hedgire.Sandeep@mgh.harvard.edu NR 17 TC 3 Z9 4 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-7071 J9 CLIN IMAG JI Clin. Imaging PD JAN-FEB PY 2013 VL 37 IS 1 BP 91 EP 96 DI 10.1016/j.clinimag.2012.03.005 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 053PD UT WOS:000312284100013 PM 23206613 ER PT J AU Gallagher, SJ Kofman, AE Huszar, JM Dannenberg, JH DePinho, RA Braun, RE Payne, CJ AF Gallagher, Shannon J. Kofman, Amber E. Huszar, Jessica M. Dannenberg, Jan-Hermen DePinho, Ronald A. Braun, Robert E. Payne, Christopher J. TI Distinct requirements for Sin3a in perinatal male gonocytes and differentiating spermatogonia SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Sin3a; Spermatogonia; DNA damage; Cell proliferation; Apoptosis; Differentiation ID PRIMORDIAL GERM-CELLS; SERTOLI-CELLS; GENE-EXPRESSION; STEM-CELLS; ORPHAN RECEPTOR; DNA-DAMAGE; MOUSE; ADULT; CHROMATIN; MICE AB Chromatin modifier Swi-independent 3a (SIN3A), together with associated histone deacetylases, influences gene expression during development and differentiation through a variety of transcription factors in a cell-specific manner. Sin3a is essential for the maintenance of inner cell mass cells of mouse blastocysts, embryonic fibroblasts, and myoblasts, but is not required for the survival of trophectoderm or Sertoli cells. To better understand how this transcriptional regulator modulates cells at different developmental stages within a single lineage, we used conditional gene targeting in mice to ablate Sin3a from perinatal quiescent male gonocytes and from postnatal differentiating spermatogonia. Mitotic germ cells expressing stimulated by retinoic acid gene 8 (Stra8) that lacked Sin3a exhibited increased DNA damage and apoptosis, yet collectively progressed through meiosis and spermiogenesis and generated epididymal sperm at approximately 50% of control levels, sufficient for normal fertility. In contrast, perinatal gonocytes lacking Sin3a underwent rapid depletion that coincided with cell cycle reentry, exhibiting 2.5-fold increased histone H3 phosphorylation upon cycling that suggested a prophase/metaphase block; germ cells were almost entirely absent two weeks after birth, resulting in sterility. Gene expression profiling of neonatal testes containing Sin3a-deleted gonocytes identified upregulated transcripts highly associated with developmental processes and pattern formation, and downregulated transcripts involved in nuclear receptor activity, including Nr4a1 (Nur77). Interestingly, Nr4a1 levels were elevated in testes containing Stra8-expressing, Sin3a-deleted sperrnatogonia. SIN3A directly binds to the Nr4a1 promoter, and Nr4a1 expression is diminished upon spermatogonial differentiation in vitro. We conclude that within the male germline, Sin3a is required for the mitotic reentry of gonocytes, but is dispensable for the maintenance of differentiating spermatogonia and subsequent spermatogenic processes. (C) 2012 Elsevier Inc. All rights reserved. C1 [Gallagher, Shannon J.; Kofman, Amber E.; Huszar, Jessica M.; Payne, Christopher J.] Northwestern Univ, Feinberg Sch Med, Human Mol Genet Program, Childrens Hosp Chicago,Res Ctr, Chicago, IL 60611 USA. [Gallagher, Shannon J.; Kofman, Amber E.; Huszar, Jessica M.; Payne, Christopher J.] Northwestern Univ, Feinberg Sch Med, Dept Pediat & Obstet & Gynecol, Chicago, IL 60611 USA. [Dannenberg, Jan-Hermen] Netherlands Canc Inst, Div Gene Regulat, Amsterdam, Netherlands. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Inst Appl Canc Sci,Dept Med Oncol, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Inst Appl Canc Sci,Dept Med, Boston, MA 02115 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Inst Appl Canc Sci,Dept Genet, Boston, MA 02115 USA. [DePinho, Ronald A.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA. [Braun, Robert E.] Jackson Lab, Bar Harbor, ME 04609 USA. RP Payne, CJ (reprint author), Northwestern Univ, Feinberg Sch Med, Human Mol Genet Program, Childrens Hosp Chicago,Res Ctr, 225 E Chicago Ave,Box 211, Chicago, IL 60611 USA. EM c-payne@northwestern.edu FU foundation of the Medical Research Institute Council at Children's Hospital of Chicago Research Center; NIH from the Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH [5R00 HD055330-05] FX The authors would like to thank Rachel Anderson for her technical assistance with these experiments, the Histology Core of the Center for Reproductive Research at Northwestern University for exemplary histology services, and the foundation of the Medical Research Institute Council at Children's Hospital of Chicago Research Center for its generous financial support. Anti-GCNA1 antibodies were kindly provided by Dr. George Enders from the University of Kansas Medical Center. C.J.P. is the recipient of an NIH Pathway-to-Independence Award from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. This work was supported by an NIH grant to C.J.P. (5R00 HD055330-05). NR 61 TC 12 Z9 12 U1 0 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JAN 1 PY 2013 VL 373 IS 1 BP 83 EP 94 DI 10.1016/j.ydbio.2012.10.009 PG 12 WC Developmental Biology SC Developmental Biology GA 053OV UT WOS:000312283200008 PM 23085237 ER PT J AU Simren, M Barbara, G Flint, HJ Spiegel, BMR Spiller, RC Vanner, S Verdu, EF Whorwell, PJ Zoetendal, EG AF Simren, Magnus Barbara, Giovanni Flint, Harry J. Spiegel, Brennan M. R. Spiller, Robin C. Vanner, Stephen Verdu, Elena F. Whorwell, Peter J. Zoetendal, Erwin G. TI Intestinal microbiota in functional bowel disorders: a Rome foundation report SO GUT LA English DT Article ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; CHAIN FATTY-ACIDS; 16S RIBOSOMAL-RNA; MULTISPECIES PROBIOTIC SUPPLEMENTATION; INDUCED VISCERAL HYPERSENSITIVITY; POSTINFECTIVE GUT DYSFUNCTION; MUCOSA-ASSOCIATED MICROBIOTA; HUMAN COLONIC MICROBIOTA AB It is increasingly perceived that gut host-microbial interactions are important elements in the pathogenesis of functional gastrointestinal disorders (FGID). The most convincing evidence to date is the finding that functional dyspepsia and irritable bowel syndrome (IBS) may develop in predisposed individuals following a bout of infectious gastroenteritis. There has been a great deal of interest in the potential clinical and therapeutic implications of small intestinal bacterial overgrowth in IBS. However, this theory has generated much debate because the evidence is largely based on breath tests which have not been validated. The introduction of culture-independent molecular techniques provides a major advancement in our understanding of the microbial community in FGID. Results from 16S rRNA-based microbiota profiling approaches demonstrate both quantitative and qualitative changes of mucosal and faecal gut microbiota, particularly in IBS. Investigators are also starting to measure host-microbial interactions in IBS. The current working hypothesis is that abnormal microbiota activate mucosal innate immune responses which increase epithelial permeability, activate nociceptive sensory pathways and dysregulate the enteric nervous system. While we await important insights in this field, the microbiota is already a therapeutic target. Existing controlled trials of dietary manipulation, prebiotics, probiotics, synbiotics and non-absorbable antibiotics are promising, although most are limited by suboptimal design and small sample size. In this article, the authors provide a critical review of current hypotheses regarding the pathogenetic involvement of microbiota in FGID and evaluate the results of microbiota-directed interventions. The authors also provide clinical guidance on modulation of gut microbiota in IBS. C1 [Simren, Magnus] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med, S-41345 Gothenburg, Sweden. [Barbara, Giovanni] Univ Bologna, Dept Med & Surg Sci, Bologna, Italy. [Barbara, Giovanni] Univ Bologna, Ctr Appl Biomed Res, Bologna, Italy. [Flint, Harry J.] Univ Aberdeen, Rowett Inst Nutr & Hlth, Microbial Ecol Grp, Aberdeen, Scotland. [Spiegel, Brennan M. R.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Spiller, Robin C.] Univ Hosp, Nottingham Digest Dis Ctr, NIHR Biomed Res Unit, Nottingham, England. [Vanner, Stephen] Queens Univ, Gastrointestinal Dis Res Unit, Kingston, ON, Canada. [Verdu, Elena F.] McMaster Univ, Farncombe Family Digest Hlth Res Inst, Hamilton, ON, Canada. [Whorwell, Peter J.] Univ Manchester, Dept Med, Wythenshawe Hosp, Manchester M13 9PL, Lancs, England. [Zoetendal, Erwin G.] Wageningen Univ, Dept Agrotechnol & Food Sci, Microbiol Lab, Wageningen, Netherlands. RP Simren, M (reprint author), Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med, S-41345 Gothenburg, Sweden. EM magnus.simren@medicine.gu.se OI spiller, robin/0000-0001-6371-4500 FU Rome Foundation, USA.; Italian Ministry of Education, University and Research; Fondazione Cassa di Risparmio; IMA, Bologna, Italy; Scottish government RESAS; Swedish Medical Research Council [13409, 21691, 21692]; Marianne and Marcus Wallenberg Foundation; University of Gothenburg, Centre for Person-Centred Care (GPCC); Sahlgrenska Academy, University of Gothenburg; Faculty of Medicine, University of Gothenburg; Shire/Movetis; Amgen; Ironwood; Canadian Institute of Health Research (CIHR); Crohn's and Colitis Foundation of Canada (CCFC); Lesaffre International; Norgine; National Institute for Health Research Biomedical Research Unit; CAG/CIHR; CCA (Canadian Celiac Association); CCFC; Nestec; Department of Medicine, McMaster University FX This work is supported by Rome Foundation, USA. In addition, the authors would like to acknowledge the following funding sources: Italian Ministry of Education, University and Research (PRIN 2009); Fondazione Cassa di Risparmio and IMA, Bologna, Italy (GB); Scottish government RESAS support (HJF); The Swedish Medical Research Council (grants 13409, 21691 and 21692), the Marianne and Marcus Wallenberg Foundation, and the University of Gothenburg, Centre for Person-Centred Care (GPCC), Sahlgrenska Academy, University of Gothenburg and by the Faculty of Medicine, University of Gothenburg (MS); Shire/Movetis, Amgen, Ironwood (BS); Canadian Institute of Health Research (CIHR) and Crohn's and Colitis Foundation of Canada (CCFC) (SV); Lesaffre International, Norgine, National Institute for Health Research Biomedical Research Unit Grant (RS); CAG/CIHR, CCA (Canadian Celiac Association), CCFC and Nestec (EFV); EFV holds a Career Award from the Department of Medicine, McMaster University. NR 266 TC 216 Z9 228 U1 15 U2 115 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD JAN PY 2013 VL 62 IS 1 BP 159 EP 176 DI 10.1136/gutjnl-2012-302167 PG 18 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 052QT UT WOS:000312214000021 PM 22730468 ER PT J AU Zietman, A AF Zietman, Anthony TI The Red Journal's Outstanding Reviewer Awards for 2012 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Zietman, A (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 3 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN 1 PY 2013 VL 85 IS 1 BP 1 EP 2 DI 10.1016/j.ijrobp.2012.11.025 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 052NN UT WOS:000312204700015 ER PT J AU Wallner, PE Ang, KK Zietman, AL Harris, JR Ibbott, GS Mahoney, MC Mezwa, DG Wilson, LD Becker, GJ AF Wallner, Paul E. Ang, K. Kian Zietman, Anthony L. Harris, Jay R. Ibbott, Geoffrey S. Mahoney, Mary C. Mezwa, Duane G. Wilson, Lynn D. Becker, Gary J. TI The American Board of Radiology Holman Research Pathway: 10-Year Retrospective Review of the Program and Participant Performance SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID RADIATION ONCOLOGY AB Introduction: In 1999, the American Board of Radiology (ABR) implemented an innovative training program track in diagnostic radiology (DR) and radiation oncology (RO) designed to stimulate development of a cadre of future academic researchers and educators in the 2 disciplines. The program was designated the Holman Research Pathway (HRP). An in-depth retrospective review of initial certification examination performance, post-training career choices, and academic productivity has not been written. This report represents a 10-year retrospective review of post-training performance of a cohort of trainees who have had sufficient time to complete their training and initial certification process and to enter practice. Methods and Materials: All pertinent proceedings of the ABR and Accreditation Council for Graduate Medical Education (ACGME) Residency Review Committees for DR and RO between 1997 and May 2011 were reviewed. Thirty-four HRP candidates who fulfilled the established evaluation criteria were identified, and their ABR data files were analyzed regarding performance on the qualifying and certifying examinations. All candidates were contacted directly to obtain a current curriculum vitae. Results: Twenty candidates in RO and 14 candidates in DR were identifiable for review. All candidates attained initial certification. At the time of analysis, 23 of 33 (66.6%) candidates were employed in full-time academic practice (1 DR candidate remained in a fellowship and was not evaluated regarding employment status). Fifteen of 20 (75%) RO candidates were in faculty positions compared with 7 of 13 (53.8%) DR trainees. Additional academic productivity metrics are reported. Conclusions: A high percentage of HRP trainees remained in academic practice and demonstrated significant academic productivity as measured by manuscript authorship and research support. Additional time and observation will be needed to determine whether these findings will be sustained by past, current, and future HRP trainees. (C) 2013 Elsevier Inc. C1 [Wallner, Paul E.] 21st Century Oncol LLC, Ft Myers, FL USA. [Wallner, Paul E.] Amer Board Radiol, Tucson, AZ USA. [Ang, K. Kian; Ibbott, Geoffrey S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Zietman, Anthony L.; Harris, Jay R.] Harvard Univ, Sch Med, Boston, MA USA. [Zietman, Anthony L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Harris, Jay R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mahoney, Mary C.] Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. [Mezwa, Duane G.] Oakland Univ, William Beaumont Sch Med, Royal Oak, MI USA. [Wilson, Lynn D.] Yale Univ, Sch Med, New Haven, CT USA. [Becker, Gary J.] Amer Board Radiol, Tucson, AZ USA. RP Wallner, PE (reprint author), 5013 Cedar Croft Lane, Bethesda, MD 20814 USA. EM pwallner@theabr.org NR 17 TC 4 Z9 4 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN 1 PY 2013 VL 85 IS 1 BP 29 EP 34 DI 10.1016/j.ijrobp.2012.04.024 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 052NN UT WOS:000312204700034 PM 22682811 ER PT J AU Shively, MJ Gardetto, NJ Kodiath, MF Kelly, A Smith, TL Stepnowsky, C Maynard, C Larson, CB AF Shively, Martha J. Gardetto, Nancy J. Kodiath, Mary F. Kelly, Ann Smith, Tom L. Stepnowsky, Carl Maynard, Charles Larson, Carolyn B. TI Effect of Patient Activation on Self-Management in Patients With Heart Failure SO JOURNAL OF CARDIOVASCULAR NURSING LA English DT Article DE congestive; health behavior; heart failure; self-management ID ASSOCIATION TASK-FORCE; QUALITY-OF-LIFE; DISEASE-MANAGEMENT; AMERICAN-COLLEGE; MEDICAL OUTCOMES; CARE; ADHERENCE; GUIDELINES; PROGRAMS; UPDATE AB Background/Objective: Few studies have examined whether chronic heart failure (HF) outcomes can be improved by increasing patient engagement (known as activation) in care and capabilities for self-care management. The objective was to determine the efficacy of a patient activation intervention compared with usual care on activation, self-care management, hospitalizations, and emergency department visits in patients with HF. Methods: This study used a randomized, 2-group, repeated-measures design. After consent was given, 84 participants were stratified by activation level and randomly assigned to usual care (n = 41) or usual care plus the intervention (n = 43). The primary outcomes and measures were patient activation using the Patient Activation Measure (PAM), self-management using the Self-Care of Heart Failure Index (SCHFI) and the Medical Outcomes Study (MOS) Specific Adherence Scale, and hospitalizations and emergency department visits. The intervention was a 6-month program to increase activation and improve HF self-management behaviors, such as adhering to medications and implementing health behavior goals. Results: Participants were primarily male (99%), were white (77%), and had New York Heart Association III stage (52%). The mean (SD) age was 66 (11) years, and 71% reported 3 or more comorbidities. The intervention group compared with the usual care group showed a significant increase in activation/PAM scores from baseline to 6 months. No significant group-by-time interactions were found for the SCHFI scales. Although the baseline MOS Specific Adherence Scale mean was lower in the intervention group, results showed a significant group-by-time effect with the intervention group improving more over time. Participants in the intervention group had fewer hospitalizations compared with the usual care group when the baseline activation/PAM level was low or high. Conclusion: This study supports the importance of targeted interventions to improve patient activation or engagement in HF care. Further work is needed related to HF self-management measurement and outcomes. C1 [Shively, Martha J.; Gardetto, Nancy J.] VA San Diego Healthcare Syst, Nursing Serv, Heart Failure Specialty Program, San Diego, CA 92161 USA. [Smith, Tom L.] Univ Calif San Diego, Sch Med, Dept Psychiat, San Diego, CA 92103 USA. [Stepnowsky, Carl] VA San Diego Healthcare Syst, Med Hlth Serv, Res & Dev, San Diego, CA 92161 USA. [Maynard, Charles] VA Puget Sound Healthcare Syst, Hlth Serv Res, Washington, DC USA. [Maynard, Charles] Univ Washington, Seattle, WA 98195 USA. RP Shively, MJ (reprint author), VA San Diego Healthcare Syst, Nursing Serv, Heart Failure Specialty Program, 3350 La Jolla Village Dr, San Diego, CA 92161 USA. EM mshively@cox.net RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service, project [04-252] FX This study was funded by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service, project 04-252. NR 39 TC 37 Z9 38 U1 4 U2 26 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0889-4655 J9 J CARDIOVASC NURS JI J. Cardiovasc. Nurs. PD JAN-FEB PY 2013 VL 28 IS 1 BP 20 EP 34 DI 10.1097/JCN.0b013e318239f9f9 PG 15 WC Cardiac & Cardiovascular Systems; Nursing SC Cardiovascular System & Cardiology; Nursing GA 055CZ UT WOS:000312394100003 PM 22343209 ER PT J AU Bartlett, JD Smith, CE AF Bartlett, J. D. Smith, C. E. TI Modulation of Cell-Cell Junctional Complexes by Matrix Metalloproteinases SO JOURNAL OF DENTAL RESEARCH LA English DT Review DE enamel; mineralized tissue/development; matrix metalloproteinases (MMPs); desomsomes; tight junctions; adherens junctions ID HYPOMATURATION AMELOGENESIS IMPERFECTA; MOUSE TOOTH DEVELOPMENT; ENAMEL ROD PATTERN; E-CADHERIN; SECRETORY AMELOBLASTS; EPITHELIAL-CELLS; RAT INCISOR; N-CADHERIN; DIFFERENTIAL EXPRESSION; MESENCHYMAL TRANSITION AB The ameloblast cell layer of the enamel organ is in contact with the forming enamel as it develops into the hardest substance in the body. Ameloblasts move in groups that slide by one another as the enamel layer thickens. Each ameloblast is responsible for the formation of one enamel rod, and the rods are the mineralized trail that moving ameloblasts leave behind. Matrix metalloproteinases (MMPs) facilitate cell movement in various tissues during development, and in this review we suggest that the tooth-specific MMP, enamelysin (MMP20), facilitates ameloblast movements during enamel development. Mmp20 null mice have thin brittle enamel with disrupted rod patterns that easily abrades from the underlying dentin. Strikingly, the Mmp20 null mouse enamel organ morphology is noticeably dysplastic during late-stage development, when MMP20 is no longer expressed. We suggest that in addition to its role of cleaving enamel matrix proteins, MMP20 also cleaves junctional complexes present on ameloblasts to foster the cell movement necessary for formation of the decussating enamel rod pattern. Therefore, inactivation of MMP20 would result in tight ameloblast cell-cell attachments that may cause maturation-stage enamel organ dysplasia. The tight ameloblast attachments would also preclude the ameloblast movement necessary to form decussating enamel rod patterns. C1 [Bartlett, J. D.] Harvard Univ, Sch Dent Med, Dept Mineralized Tissue Biol, Forsyth Inst, Cambridge, MA 02138 USA. [Bartlett, J. D.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Cambridge, MA 02138 USA. [Smith, C. E.] McGill Univ, Facil Electron Microscopy Res, Dept Anat & Cell Biol, Montreal, PQ, Canada. [Smith, C. E.] McGill Univ, Fac Dent, Montreal, PQ, Canada. RP Bartlett, JD (reprint author), Harvard Univ, Sch Dent Med, Dept Mineralized Tissue Biol, Forsyth Inst, Cambridge, MA 02138 USA. EM jbartlett@forsyth.org FU NIDCR [DE016276] FX Portions of the research reported here were supported by NIDCR research grant DE016276 (JDB). We thank James P. Simmer and the University of Michigan Dental Research Laboratory for the histological material used to make Fig. 1. The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. NR 60 TC 18 Z9 19 U1 1 U2 14 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JAN PY 2013 VL 92 IS 1 BP 10 EP 17 DI 10.1177/0022034512463397 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 052PH UT WOS:000312209700003 PM 23053846 ER PT J AU Bauer, AS Bae, DS Brustowicz, KA Waters, PM AF Bauer, Andrea S. Bae, Donald S. Brustowicz, Katherine A. Waters, Peter M. TI Intra-articular Corrective Osteotomy of Humeral Lateral Condyle Malunions in Children: Early Clinical and Radiographic Results SO JOURNAL OF PEDIATRIC ORTHOPAEDICS LA English DT Article DE lateral condyle fracture; malunion; osteotomy ID NON-UNION; FRACTURES AB Background: Intra-articular malunions of pediatric humeral lateral condyle fractures may lead to pain, loss of motion and function, deformity, and elbow arthritis. Little information is available, however, regarding the treatment of symptomatic articular malunions. The purpose of this investigation is to report early results of intra-articular osteotomy of lateral condyle malunions in children. Methods: Seven patients who underwent intra-articular osteotomies for lateral condyle malunions were evaluated. Clinical records and radiographs were reviewed for demographics, fracture characteristics, initial fracture care, surgical technique, and early clinical and radiographic results. Outcomes were classified according to the Dhillon score. Results: Mean age at time of injury was 8.1 years (range, 4.3 to 11.4 y). Three patients had Milch type I fractures; 4 had Milch type II fractures. The mean interval from injury to osteotomy was 10 months. Two patients were initially treated with cast immobilization, and 5 underwent surgical treatment with either percutaneous pin fixation (n = 2) or open reduction internal fixation (n = 3). Before osteotomy, mean arc of elbow motion was 60 degrees (range, 40 to 100 degrees), average Dhillon score was 4 (range, 3 to 6), and average Baumann angle was 75 degrees. Postoperatively, mean elbow arc of motion improved to 105 degrees (range, 60 to 140 degrees) (P = 0.028), and mean Dhillon score improved to 5.6 (range, 3 to 7) (P = 0.02). There was a trend toward better postoperative Dhillon scores in patients with Milch type I (mean 7) versus Milch type II injuries (mean 4.5) (P = 0.12). Average Baumann angle postoperatively was 85 degrees. Two patients had persistent radiographic evidence of osteonecrosis of the capitellum or trochlea at most recent follow-up, consistent with preoperative imaging. Conclusions: Intra-articular corrective osteotomy may improve range of motion in patients with functionally limiting elbow stiffness due to lateral condyle malunion. Milch I fracture malunions may be more amenable to surgical correction than fractures extending into the trochlea. Preservation of soft tissue attachments to the lateral condylar fragment is recommended to minimize the risk of subsequent osteonecrosis. C1 [Bae, Donald S.; Brustowicz, Katherine A.; Waters, Peter M.] Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Bauer, Andrea S.] Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA. RP Bae, DS (reprint author), Childrens Hosp, Dept Orthopaed Surg, 300 Longwood Ave,Hunnewell 2, Boston, MA 02115 USA. EM donald.bae@childrens.harvard.edu NR 8 TC 4 Z9 4 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-6798 J9 J PEDIATR ORTHOPED JI J. Pediatr. Orthop. PD JAN-FEB PY 2013 VL 33 IS 1 BP 20 EP 25 DI 10.1097/BPO.0b013e318279c4cd PG 6 WC Orthopedics; Pediatrics SC Orthopedics; Pediatrics GA 053FJ UT WOS:000312256100006 PM 23232374 ER PT J AU Biederman, J Faraone, SV Petty, C Martelon, M Woodworth, KY Wozniak, J AF Biederman, Joseph Faraone, Stephen V. Petty, Carter Martelon, MaryKate Woodworth, K. Yvonne Wozniak, Janet TI Further evidence that pediatric-onset bipolar disorder comorbid with ADHD represents a distinct subtype: Results from a large controlled family study SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Bipolar disorder; Attention-deficit hyperactivity disorder; Family-genetic; Children ID DEFICIT HYPERACTIVITY DISORDER; DOPAMINE TRANSPORTER GENE; PSYCHIATRIC CO-MORBIDITY; I DISORDER; CLINICAL CHARACTERISTICS; CHILDREN; MANIA; ADOLESCENTS; ASSOCIATION; SYMPTOMS AB We used familial risk analysis to clarify the diagnostic comorbidity between pediatric BP-I disorder and ADHD, testing the hypothesis that pediatric-BP-I disorder comorbid with ADHD represents a distinct subtype. Structured diagnostic interviews were used to obtain DSM-IV psychiatric diagnoses on first-degree relatives (n = 726) of referred children and adolescents satisfying diagnostic criteria for BP-I disorder (n = 239). For comparison, diagnostic information on the first-degree relatives (N = 511) of non-bipolar ADHD children (N = 162) and the first degree relatives (N = 411) of control children (N = 136) with neither ADHD nor BP-I disorder were examined. BP-I disorder and ADHD in probands bred true irrespective of the comorbidity with the other disorder. We also found that the comorbid condition of BP-I disorder plus ADHD also bred true in families, and the two disorders co-segregated among relatives. This large familial risk analysis provides compelling evidence that pediatric BP-I disorder comorbid with ADHD represents a distinct familial subtype. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Biederman, Joseph; Petty, Carter; Martelon, MaryKate; Woodworth, K. Yvonne; Wozniak, Janet] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Biederman, Joseph; Wozniak, Janet] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA. [Biederman, Joseph; Petty, Carter; Martelon, MaryKate; Woodworth, K. Yvonne; Wozniak, Janet] Massachusetts Gen Hosp, Clin & Res Program Adult ADHD, Boston, MA 02114 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, 55 Fruit St,Yawkey 6A, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU Elminda; Janssen; McNeil; Shire; Fundacion Dr. Manuel Camelo A.C. in Monterrey Mexico; Abbott; Alza; AstraZeneca; Boston University; Bristol Myers Squibb; Celltech; Cephalon; Eli Lilly and Co.; Esai; Fundacion Areces (Spain); Forest; Glaxo; Gliatech; Hastings Center; Medice Pharmaceuticals (Germany); Merck; MMC Pediatric; NARSAD; NIDA; New River; NICHD; NIMH; Novartis; Noven; Neurosearch; Organon; Otsuka; Pfizer; Pharmacia; Phase V Communications; Physicians Academy; Prechter Foundation; Quantia Communications; Reed Exhibitions; Spanish Child Psychiatry Association; Stanley Foundation; UCB Pharma Inc.; Veritas; Wyeth; Alcobra; Eli Lilly; Johnson and Johnson; UCB; Zeo; Sunovion; GlaxoSmithKline; Axon Labs; Boehringer-Ingelheim; Covance; Impax; Jazz Pharmaceuticals; King; Luitpold; Neurogen; Novadel Pharma; Sanofi-Aventis; Sepracor; Sunovian; Takeda; UCB (Schwarz) Pharma; National Institutes of Health (NIH) [K08MH001503, R01MH066237, R01MH050657, R01HD036317]; Heinz C. Prechter Bipolar Research Fund; Susan G. Berk Endowed Fund for Juvenile Bipolar Disorder FX Dr. Joseph Biederman is currently receiving research support from the following sources: Elminda, Janssen, McNeil, and Shire. In 2011, Dr. Joseph Biederman gave a single unpaid talk for Juste Pharmaceutical Spain, received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course, and received an honorarium for presenting at an international scientific conference on ADHD. He also received an honorarium from Cambridge University Press for a chapter publication. Dr. Biederman received departmental royalties from a copyrighted rating scale used for ADHD diagnoses, paid by Eli Lilly, Shire and AstraZeneca; these royalties are paid to the Department of Psychiatry at MGH. In 2010, Dr. Joseph Biederman received a speaker's fee from a single talk given at Fundacion Dr. Manuel Camelo A.C. in Monterrey Mexico. Dr. Biederman provided single consultations for Shionogi Pharma Inc. and Cipher Pharmaceuticals Inc.: the honoraria for these consultations were paid to the Department of Psychiatry at the MGH. Dr. Biederman received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course. In previous years, Dr.Joseph Biederman received research support, consultation fees, or speaker's fees for/from the following additional sources: Abbott, Alza, AstraZeneca, Boston University, Bristol Myers Squibb, Celltech, Cephalon, Eli Lilly and Co., Esai, Fundacion Areces (Spain), Forest, Glaxo, Gliatech, Hastings Center, Janssen, McNeil, Medice Pharmaceuticals (Germany), Merck, MMC Pediatric, NARSAD, NIDA, New River, NICHD, NIMH, Novartis, Noven, Neurosearch, Organon, Otsuka, Pfizer, Pharmacia, Phase V Communications, Physicians Academy, The Prechter Foundation, Quantia Communications, Reed Exhibitions, Shire, the Spanish Child Psychiatry Association, The Stanley Foundation, UCB Pharma Inc., Veritas, and Wyeth.; In the past year, Dr. Faraone received consulting income and research support from Shire and Alcobra and research support from the National Institutes of Health (NIH). In previous years, he received consulting fees or was on Advisory Boards or participated in continuing medical education programs sponsored by: Shire, McNeil, Janssen, Novartis, Pfizer and Eli Lilly. Dr. Faraone receives royalties from books published by Guilford Press: Straight Talk about Your Child's Mental Health and Oxford University Press: Schizophrenia: The Facts.; In 2011, Janet Wozniak MD has received research support from McNeil and Shire. In the past she has received research support, consultation fees or speaker's fees from: Eli Lilly, Janssen, Johnson and Johnson, McNeil, Pfizer, Shire. She is the author of the book, "Is Your Child Bipolar" published May 2009, Bantam Books. In 2011, her spouse John Winkelman MD, PhD received consultation fees from Pfizer, UCB, Zeo, and Sunovion. He received research support from GlaxoSmithKline. In the past, he has received research support, consultation fees or speaker's fees from: Axon Labs, Boehringer-Ingelheim, Covance, Cephalon, Eli Lilly, GlaxoSmithKline, Impax, Jazz Pharmaceuticals, King, Luitpold, Novartis, Neurogen, Novadel Pharma, Pfizer, Sanofi-Aventis, Sepracor, Sunovian, Takeda, UCB (Schwarz) Pharma, Wyeth, Zeo.; This work was supported by NIH grants K08MH001503 and R01MH066237 to Dr Wozniak and R01MH050657 and R01HD036317 to Dr Biederman. This work was also supported by a grant from the Heinz C. Prechter Bipolar Research Fund, the support of members of the MGH Pediatric Psychopharmacology Council and the Susan G. Berk Endowed Fund for Juvenile Bipolar Disorder. NR 40 TC 10 Z9 10 U1 0 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD JAN PY 2013 VL 47 IS 1 BP 15 EP 22 DI 10.1016/j.jpsychires.2012.08.002 PG 8 WC Psychiatry SC Psychiatry GA 054OZ UT WOS:000312354400003 PM 22979994 ER PT J AU Inslicht, SS Metzler, TJ Garcia, NM Pineles, SL Milad, MR Orr, SP Marmar, CR Neylan, TC AF Inslicht, Sabra S. Metzler, Thomas J. Garcia, Natalia M. Pineles, Suzanne L. Milad, Mohammed R. Orr, Scott P. Marmar, Charles R. Neylan, Thomas C. TI Sex differences in fear conditioning in posttraumatic stress disorder SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Sex differences; Learning; Conditioning; Fear; Posttraumatic stress disorder; Galvanic skin response ID CHILDHOOD TRAUMA; EXTINCTION; PTSD; RESPONSES; VETERANS; RATS; EXPRESSION; EXPOSURE; EXPLICIT; RECEPTOR AB Background: Women are twice as likely as men to develop Posttraumatic Stress Disorder (PTSD). Abnormal acquisition of conditioned fear has been suggested as a mechanism for the development of PTSD. While some studies of healthy humans suggest that women are either no different or express less conditioned fear responses during conditioning relative to men, differences in the acquisition of conditioned fear between men and women diagnosed with PTSD has not been examined. Methods: Thirty-one participants (18 men; 13 women) with full or subsyndromal PTSD completed a fear conditioning task. Participants were shown computer-generated colored circles that were paired (CS+) or unpaired (CS-) with an aversive electrical stimulus and skin conductance levels were assessed throughout the task. Results: Repeated measures ANOVA indicated a significant sex by stimulus interaction during acquisition. Women had greater differential conditioned skin conductance responses (CS+ trials compared to CS- trials) than did men, suggesting greater acquisition of conditioned fear in women with PTSD. Conclusions: In contrast to studies of healthy individuals, we found enhanced acquisition of conditioned fear in women with PTSD. Greater fear conditioning in women may either be a pre-existing vulnerability trait or an acquired phenomenon that emerges in a sex-dependent manner after the development of PTSD. Characterizing the underlying mechanisms of these differences is needed to clarify sex-related differences in the pathophysiology of PTSD. Published by Elsevier Ltd. C1 [Inslicht, Sabra S.; Metzler, Thomas J.; Garcia, Natalia M.; Neylan, Thomas C.] San Francisco VA Med Ctr, San Francisco, CA USA. [Inslicht, Sabra S.; Metzler, Thomas J.; Neylan, Thomas C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Pineles, Suzanne L.] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA USA. [Pineles, Suzanne L.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Milad, Mohammed R.; Orr, Scott P.] Massachusetts Gen Hosp, Charlestown, MA USA. [Milad, Mohammed R.; Orr, Scott P.] Harvard Univ, Sch Med, Charlestown, MA USA. [Marmar, Charles R.] NYU, Langone Med Ctr, New York, NY USA. RP Inslicht, SS (reprint author), Vet Affairs Med Ctr, PTSD Res Program, 4150 Clement St,116P, San Francisco, CA 94121 USA. EM Sabra.Inslicht@ucsf.edu FU Department of Defense; Department of Veteran Affairs CSRD [CDA-2-037-07F, CDA-2-042-07F]; Mental Illness Research and Education Clinical Center (MIRECC) of the US Veterans Health Administration; Office of the Director, National Institutes of Health [KL2 RR024130] FX Dr. Neylan has received experimental medication from Actelion for a study funded by the Department of Defense. The authors report no other financial, personal, or other relationships with any entities that might inappropriately influence, or be perceived to have influenced the research presented in this manuscript.; This research was supported by a grant from the Department of Veteran Affairs CSR&D (CDA-2-037-07F) to Dr. Inslicht, and the Mental Illness Research and Education Clinical Center (MIRECC) of the US Veterans Health Administration. Resources and the use of facilities were provided by the Veterans Administration Medical Center, San Francisco California and the National Center for Research Resources, the National Center for Advancing Translational Sciences, and the Office of the Director, National Institutes of Health, through a UCSF-CTSI Grant (#KL2 RR024130). Dr. Pineles was supported by the Department of Veteran Affairs CSR&D (CDA-2-042-07F). The sponsors had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the sponsors. NR 42 TC 35 Z9 38 U1 5 U2 30 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD JAN PY 2013 VL 47 IS 1 BP 64 EP 71 DI 10.1016/j.jpsychires.2012.08.027 PG 8 WC Psychiatry SC Psychiatry GA 054OZ UT WOS:000312354400009 PM 23107307 ER PT J AU Sher, L Mann, JJ Oquendo, MA AF Sher, Leo Mann, J. John Oquendo, Maria A. TI Sleep, psychiatric disorders and suicide SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Letter ID BEHAVIOR C1 [Sher, Leo] James J Peters Vet Adm Med Ctr, New York, NY 10468 USA. [Sher, Leo] Mt Sinai Sch Med, New York, NY 10468 USA. [Sher, Leo; Mann, J. John; Oquendo, Maria A.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Sher, Leo; Mann, J. John; Oquendo, Maria A.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. RP Sher, L (reprint author), James J Peters Vet Adm Med Ctr, 130 W Kingsbridge Rd, New York, NY 10468 USA. EM Leo.Sher@mssm.edu FU NIMH NIH HHS [P50 MH090964] NR 5 TC 0 Z9 0 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD JAN PY 2013 VL 47 IS 1 BP 135 EP 135 DI 10.1016/j.jpsychires.2012.09.011 PG 1 WC Psychiatry SC Psychiatry GA 054OZ UT WOS:000312354400019 PM 23157799 ER PT J AU Gee, SN Zakhary, L Keuthen, N Kroshinsky, D Kimball, AB AF Gee, Sarah N. Zakhary, Lisa Keuthen, Nancy Kroshinsky, Daniela Kimball, Alexa Boer TI A survey assessment of the recognition and treatment of psychocutaneous disorders in the outpatient dermatology setting: How prepared are we? SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE antidepressants; depression; health care surveys; mental illness; psychiatry; psychocutaneous disease; psychodermatology; psychoneuroimmunology; psychotropics ID LICHEN SIMPLEX CHRONICUS; PRURIGO NODULARIS; POSTHERPETIC NEURALGIA; HERPES-ZOSTER; GABAPENTIN; DEPRESSION; MIRTAZAPINE; ADOLESCENTS; KNOWLEDGE; LYMPHOMA AB Background: Dermatologists provide the bulk of psychocutaneous care; however, recent studies suggest that dermatologists believe they are largely underprepared to treat most psychocutaneous conditions. Objective: We sought to identify gaps in psychodermatologic knowledge among practicing dermatologists in two academic institutions. Methods: An online survey was sent to 59 dermatologists at the Massachusetts General Hospital (Boston, MA) and Brigham and Women's Hospital (Boston, MA) from July 2010 through October 2011. Results: The response rate was 40 of 59 (68%). More than 50% of dermatologists were comfortable making diagnoses for 8 of 10 psychocutaneous disorders. In all, 57% were comfortable making a diagnosis of depression. A total of 11% were comfortable starting antidepressants; 3%, antipsychotics; and 66%, medications for neuropathic pain. In all, 72%, 68%, and 21% of dermatologists never prescribe antidepressants, antipsychotics, or medications for neuropathic pain, respectively. Only 38% believed they were successful treating compulsive skin picking; 15%, body dysmorphic disorder; 27%, delusions of parasitosis; and 24%, depression. Limitations: Limitations include small sample size, data extraction from an academic setting, self-reporting of outcome measures, and response bias. Conclusion: Although the majority of the physicians surveyed believed they were capable of diagnosing psychocutaneous disease, very few were comfortable starting psychotropics or thought they were successful treating such conditions. (J Am Acad Dermatol 2013;68:47-52.) C1 [Gee, Sarah N.; Kroshinsky, Daniela; Kimball, Alexa Boer] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Zakhary, Lisa; Keuthen, Nancy] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Gee, Sarah N.; Zakhary, Lisa; Keuthen, Nancy; Kroshinsky, Daniela; Kimball, Alexa Boer] Harvard Univ, Sch Med, Boston, MA USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 50 Staniford St,Suite 246, Boston, MA 02114 USA. EM harvardskinstudies@partners.org NR 23 TC 3 Z9 3 U1 3 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JAN PY 2013 VL 68 IS 1 BP 47 EP 52 DI 10.1016/j.jaad.2012.04.007 PG 6 WC Dermatology SC Dermatology GA 053KR UT WOS:000312270900010 PM 22954748 ER PT J AU Werth, VP AF Werth, Victoria P. TI The safe and appropriate use of systemic glucocorticoids in treating dermatologic disease SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Editorial Material C1 [Werth, Victoria P.] Hosp Univ Penn, Dept Dermatol, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Werth, Victoria P.] Univ Penn, Philadelphia, PA 19104 USA. RP Werth, VP (reprint author), Hosp Univ Penn, Dept Dermatol, Philadelphia Vet Affairs Med Ctr, PCAM Suite 1-330S,3400 Civic Ctr Blvd, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu NR 0 TC 1 Z9 1 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JAN PY 2013 VL 68 IS 1 BP 177 EP 178 DI 10.1016/j.jaad.2012.09.002 PG 2 WC Dermatology SC Dermatology GA 053KR UT WOS:000312270900029 PM 23244375 ER PT J AU Gandy, S DeKosky, ST AF Gandy, Sam DeKosky, Steven T. TI 2012: the year in dementia SO LANCET NEUROLOGY LA English DT Editorial Material ID ALZHEIMERS-DISEASE C1 [Gandy, Sam] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Gandy, Sam] James J Peters VA Med Ctr, New York, NY 10029 USA. [DeKosky, Steven T.] Univ Virginia, Charlottesville, VA 22908 USA. RP Gandy, S (reprint author), Icahn Sch Med Mt Sinai, New York, NY 10029 USA. EM samuel.gandy@mssm.edu; dekosky@virginia.edu FU NIA NIH HHS [P50 AG005138] NR 12 TC 2 Z9 2 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD JAN PY 2013 VL 12 IS 1 BP 4 EP 6 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 055PR UT WOS:000312429400003 PM 23237888 ER PT J AU Diab, A Zickl, L Abdel-Wahab, O Jhanwar, S Gulam, MA Panageas, KS Patel, JP Jurcic, J Maslak, P Paietta, E Mangan, JK Carroll, M Fernandez, HF Teruya-Feldstein, J Luger, SM Douer, D Litzow, MR Lazarus, HM Rowe, JM Levine, RL Tallman, MS AF Diab, Adi Zickl, Lynette Abdel-Wahab, Omar Jhanwar, Suresh Gulam, Manjit A. Panageas, Katherine S. Patel, Jay P. Jurcic, Joseph Maslak, Peter Paietta, Elisabeth Mangan, James K. Carroll, Martin Fernandez, Hugo F. Teruya-Feldstein, Julie Luger, Selina M. Douer, Dan Litzow, Mark R. Lazarus, Hillard M. Rowe, Jacob M. Levine, Ross L. Tallman, Martin S. TI Acute myeloid leukemia with translocation t(8;16) presents with features which mimic acute promyelocytic leukemia and is associated with poor prognosis SO LEUKEMIA RESEARCH LA English DT Article DE Leukemia; APL; t(8;16); AML; Therapy-related AML ID STEM-CELL TRANSPLANTATION; OF-THE-LITERATURE; CONGENITAL LEUKEMIA; MONOCYTIC LEUKEMIA; THERAPY; AML; T(8/16)(P11,P13); ACETYLTRANSFERASE; REARRANGEMENT; INTENSITY AB Previous small series have suggested that acute myeloid leukemia with t(8;16) is a distinct morphologic and clinical entity associated with poor prognosis. We describe 18 patients with t(8;16) AML, including their clinical, cytomorphologic, immunophenotypic and cytogenetic features. Half of the patients had extramedullary disease, most commonly leukemia cutis, which often preceded bone marrow involvement and six had therapy-related AML. Patients with t(8;16) AML commonly present with clinical and pathological features that mimic APL, with promyelocytes and promyeloblast-like cells and coagulopathy in most patients. Several patients also presented with marrow histiocytes with hemophagocytosis and erythrophagocytosis. Comprehensive molecular analysis for co-occurring genetic alterations revealed a somatic mutation in RUNX1 in 1 of 6 t(8;16) patients with no known AML mutation in the remaining five t(8;16) patients. This suggests that the t(8;16) translocation could be sufficient to induce hematopoietic cell transformation to AML without acquiring other genetic alteration. These data further support classifying t(8;16) AML as a clinically and molecularly defined subtype of AML marked by characteristic clinical and cytomorphologic features that mimic APL, and is associated with very poor survival. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Diab, Adi; Abdel-Wahab, Omar; Jhanwar, Suresh; Gulam, Manjit A.; Jurcic, Joseph; Maslak, Peter; Douer, Dan; Levine, Ross L.; Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, New York, NY 10021 USA. [Teruya-Feldstein, Julie] Mem Sloan Kettering Canc Ctr, Dept Pathol, Leukemia Serv, New York, NY 10021 USA. [Abdel-Wahab, Omar; Patel, Jay P.; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. [Zickl, Lynette] Dana Farber Canc Inst, Dept Epidemiol & Biostat, Brookline, MA USA. [Zickl, Lynette] ECOG Stat Ctr, Brookline, MA USA. [Panageas, Katherine S.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Paietta, Elisabeth] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Oncol, Bronx, NY 10467 USA. [Paietta, Elisabeth] ECOG Leukem Translat Studies Lab, Bronx, NY USA. [Fernandez, Hugo F.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Blood & Marrow Transplantat, Tampa, FL 33682 USA. [Mangan, James K.; Carroll, Martin; Luger, Selina M.] Univ Penn, Div Hematol Oncol, Philadelphia, PA 19104 USA. [Litzow, Mark R.] Mayo Clin, Rochester, MN USA. [Lazarus, Hillard M.] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. [Rowe, Jacob M.] Shaare Zedek Med Ctr, Dept Hematol, Jerusalem, Israel. RP Diab, A (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, 1275 York Ave, New York, NY 10021 USA. EM diaba@mskcc.org OI Maslak, Peter/0000-0003-1949-5819; Abdel-Wahab, Omar/0000-0002-3907-6171 FU Memorial Sloan-Kettering Cancer Center FX Funding from the Peter Solomon Fund at Memorial Sloan-Kettering Cancer Center. NR 27 TC 8 Z9 8 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD JAN PY 2013 VL 37 IS 1 BP 32 EP 36 DI 10.1016/j.leukres.2012.08.025 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 052KP UT WOS:000312196800007 PM 23102703 ER PT J AU McDougle, CJ Carlezon, WA AF McDougle, Christopher J. Carlezon, William A., Jr. TI Neuroinflammation and Autism: Toward Mechanisms and Treatments SO NEUROPSYCHOPHARMACOLOGY LA English DT Editorial Material ID CHILDREN C1 [McDougle, Christopher J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [McDougle, Christopher J.] MassGen Hosp Children, Boston, MA USA. [McDougle, Christopher J.; Carlezon, William A., Jr.] Harvard Univ, Sch Med, Boston, MA USA. [Carlezon, William A., Jr.] McLean Hosp, Dept Psychiat, Belmont, MA 02178 USA. RP McDougle, CJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM cmcdougle@partners.org; bcarlezon@mclean.harvard.edu FU NIMH NIH HHS [MH063266, MH077600, MH083739, R01 MH063266, R01 MH077600, R01 MH083739] NR 6 TC 4 Z9 4 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2013 VL 38 IS 1 BP 241 EP 242 DI 10.1038/npp.2012.174 PG 3 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 051BP UT WOS:000312099500021 PM 23147483 ER PT J AU Wynn, JK Jahshan, C Altshuler, LL Glahn, DC Green, MF AF Wynn, J. K. Jahshan, C. Altshuler, L. L. Glahn, D. C. Green, M. F. TI Event-related potential examination of facial affect processing in bipolar disorder and schizophrenia SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Bipolar disorder; event-related potentials; facial affect; schizophrenia ID AFFECT RECOGNITION DEFICITS; PSYCHIATRIC RATING-SCALE; QUALITY-ASSURANCE; FACE PERCEPTION; N170 COMPONENT; EMOTION; EXPRESSIONS; DEPRESSION; EXPLICIT AB Background. Patients with bipolar disorder exhibit consistent deficits in facial affect identification at both behavioral and neural levels. However, little is known about which stages of facial affect processing are dysfunctional. Method. Event-related potentials (ERPs), including amplitude and latency, were used to evaluate two stages of facial affect processing : N170 to examine structural encoding of facial features and N250 to examine decoding of facial features in 57 bipolar disorder patients, 30 schizophrenia patients and 30 healthy controls. Three conditions were administered : participants were asked to identify the emotion of a face, the gender of a face, or whether a building was one or two stories tall. Results. Schizophrenia patients' emotion identification accuracy was lower than that of bipolar patients and healthy controls. N170 amplitude was significantly smaller in schizophrenia patients compared to bipolar patients and healthy controls, which did not differ from each other. Both patient groups had significantly longer N170 latency compared to healthy controls. For N250, both patient groups showed significantly smaller amplitudes compared with controls, but did not differ from each other. Bipolar patients showed longer N250 latency than healthy controls; patient groups did not differ from each other. Conclusions. Bipolar disorder patients have relatively intact structural encoding of faces (N170) but are impaired when decoding facial features for complex judgments about faces (N250 latency and amplitude), such as identifying emotion or gender. C1 [Wynn, J. K.; Jahshan, C.; Green, M. F.] VA Greater Los Angeles Healthcare Syst, MIRECC, Los Angeles, CA 90073 USA. [Wynn, J. K.; Altshuler, L. L.; Green, M. F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Glahn, D. C.] Yale Univ, Sch Med, New Haven, CT USA. RP Wynn, JK (reprint author), VA Greater Los Angeles Healthcare Syst, MIRECC, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jkwynn@ucla.edu RI Wynn, Jonathan/H-3749-2014 OI Wynn, Jonathan/0000-0002-1763-8540 FU National Institute of Mental Health [MH089634] FX This work was supported by grants from the National Institute of Mental Health (MH089634 to M.F.G.). We thank C. Gibson, C. Tripp, K. Weiner, M. McGee, C. Waldon and A. Bender for their assistance with recruitment and testing. NR 37 TC 19 Z9 20 U1 3 U2 10 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD JAN PY 2013 VL 43 IS 1 BP 109 EP 117 DI 10.1017/S0033291712001006 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 053GX UT WOS:000312260500010 PM 22583955 ER PT J AU Seidman, LJ Cherkerzian, S Goldstein, JM Agnew-Blais, J Tsuang, MT Buka, SL AF Seidman, L. J. Cherkerzian, S. Goldstein, J. M. Agnew-Blais, J. Tsuang, M. T. Buka, S. L. TI Neuropsychological performance and family history in children at age 7 who develop adult schizophrenia or bipolar psychosis in the New England Family Studies SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Bipolar psychosis; neurocognition; pre-morbid; schizophrenia ID HIGH-RISK; PREMORBID IQ; GENETIC VULNERABILITY; BIRTH COHORT; DISORDER; CHILDHOOD; COMPLICATIONS; INTELLIGENCE; POPULATION; IMPAIRMENT AB Background. Persons developing schizophrenia (SCZ) manifest various pre-morbid neuropsychological deficits, studied most often by measures of IQ. Far less is known about pre-morbid neuropsychological functioning in individuals who later develop bipolar psychoses (BP). We evaluated the specificity and impact of family history (FH) of psychosis on pre-morbid neuropsychological functioning. Method. We conducted a nested case-control study investigating the associations of neuropsychological data collected systematically at age 7 years for 99 adults with psychotic diagnoses (including 45 SCZ and 35 BP) and 101 controls, drawn from the New England cohort of the Collaborative Perinatal Project (CPP). A mixed-model approach evaluated full-scale IQ, four neuropsychological factors derived from principal components analysis (PCA), and the profile of 10 intelligence and achievement tests, controlling for maternal education, race and intra-familial correlation. We used a deviant responder approach (<10th percentile) to calculate rates of impairment. Results. There was a significant linear trend, with the SCZ group performing worst. The profile of childhood deficits for persons with SCZ did not differ significantly from BP. Neuropsychological impairment was identified in 42.2% of SCZ, 22.9% of BP and 7% of controls. The presence of psychosis in first-degree relatives (FH+) significantly increased the severity of childhood impairment for SCZ but not for BP. Conclusions. Pre-morbid neuropsychological deficits are found in a substantial proportion of children who later develop SCZ, especially in the SCZ FH+ subgroup, but less so in BP, suggesting especially impaired neurodevelopment underlying cognition in pre-SCZ children. Future work should assess genetic and environmental factors that explain this FH effect. C1 [Seidman, L. J.] Harvard Univ, Beth Israel Deaconess Med Ctr,Neuropsychol Lab, Massachusetts Mental Hlth Ctr,Div Publ Psychiat, Dept Psychiat,Med Sch,Commonwealth Res Ctr, Boston, MA 02115 USA. [Seidman, L. J.; Goldstein, J. M.; Tsuang, M. T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. [Seidman, L. J.; Goldstein, J. M.; Tsuang, M. T.; Buka, S. L.] Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. [Cherkerzian, S.; Goldstein, J. M.] Harvard Univ, Connors Ctr Womens Hlth & Gender Biol, Sch Med, Dept Psychiat,Div Womens Hlth, Boston, MA 02115 USA. [Agnew-Blais, J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Tsuang, M. T.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genom, La Jolla, CA 92093 USA. [Tsuang, M. T.] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA. [Tsuang, M. T.] Vet Med Res Fdn, San Diego, CA USA. [Buka, S. L.] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. RP Seidman, LJ (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr,Neuropsychol Lab, Massachusetts Mental Hlth Ctr,Div Publ Psychiat, Dept Psychiat,Med Sch,Commonwealth Res Ctr, 5th Floor,75 Fenwood Rd, Boston, MA 02115 USA. EM lseidman@bidmc.harvard.edu RI Buka, Stephen/H-7335-2014; Agnew-Blais, Jessica/L-9236-2015 OI Buka, Stephen/0000-0002-8578-9308; Agnew-Blais, Jessica/0000-0002-0755-6867 FU Stanley Medical Research Institute; National Association for Research on Schizophrenia and Depression; National Institute of Mental Health [MH-63951, MH-56956, MH-50647, T32 MH-017119]; Commonwealth Research Center, Massachusetts Department of Mental Health [SCDMH82101008006] FX This research was supported by grants from the Stanley Medical Research Institute (L.J.S. and S.L.B.), the National Association for Research on Schizophrenia and Depression (L.J.S.), the National Institute of Mental Health, MH-63951 (L.J.S.), MH-56956 (J.M.G.), MH-50647 (M. T. T. and J.M.G.), T32 MH-017119 (J.A.B.) and the Commonwealth Research Center (SCDMH82101008006), Massachusetts Department of Mental Health (L.J.S.). We thank the following people for help in carrying out this study: L. Barker, J. Burbridge, M. Cirillo, L. Denny, J.-A. Donatelli, C. Fetterer, J. Koch, W. S. Kremen, E. Olson, C. Provencale, A. Peters Remington and W. S. Stone. NR 44 TC 34 Z9 34 U1 2 U2 24 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD JAN PY 2013 VL 43 IS 1 BP 119 EP 131 DI 10.1017/S0033291712000773 PG 13 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 053GX UT WOS:000312260500011 PM 22575089 ER PT J AU Hong, TS Wo, JY Kwak, EL AF Hong, Theodore S. Wo, Jennifer Y. Kwak, Eunice L. TI Targeted Therapies with Chemoradiation in Esophageal Cancer: Development and Future Directions SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID METASTATIC COLORECTAL-CANCER; CELL LUNG-CANCER; HER2-POSITIVE BREAST-CANCER; MET AMPLIFICATION; PHASE-II; GASTRIC-CANCER; ADJUVANT CHEMOTHERAPY; PLUS CETUXIMAB; ADENOCARCINOMA; BEVACIZUMAB AB Targeted therapies have been studied in combination with chemoradiation therapy for esophageal and gastroesophageal junction cancers. To date, the Human Epidermal Growth Factor Receptor 2 (HER2) HER2, epidermal growth factor receptor, and vascular endothelial growth factor pathways have been most extensively studied in esophagogastric cancers. However, despite strong preclinical rationale and evidence of activity in other diseases, the efficacy of these agents has been mixed when studied in the metastatic setting or in combination with chemoradiation. In this review, the history of the development of targeted therapies in esophagogastric cancers is reviewed, with a specific focus on the incorporation of these agents with chemoradiation. Additionally, more recently identified targets of interest in esophagogastric cancers, including c-MET, heat shock protein 90, and Sonic hedgehog, are discussed in the context of chemoradiation. Semin Radiat Oncol 23:31-37 (C) 2013 Elsevier Inc. All rights reserved. C1 [Hong, Theodore S.; Wo, Jennifer Y.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Kwak, Eunice L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Hong, TS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM tshong1@partners.org NR 54 TC 9 Z9 11 U1 0 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1053-4296 EI 1532-9461 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD JAN PY 2013 VL 23 IS 1 BP 31 EP 37 DI 10.1016/j.semradonc.2012.09.004 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 055QV UT WOS:000312432400006 PM 23207045 ER PT J AU Mai, XM Langhammer, A Chen, Y Camargo, CA AF Mai, Xiao-Mei Langhammer, Arnulf Chen, Yue Camargo, Carlos A., Jr. TI Cod liver oil intake and incidence of asthma in Norwegian adults-the HUNT study SO THORAX LA English DT Article ID VITAMIN-D INTAKE; BONE-MINERAL DENSITY; POSTMENOPAUSAL WOMEN; 5-YEAR-OLD CHILDREN; ALLERGIC DISEASES; SERUM RETINOL; RISK; PREGNANCY; SUPPLEMENTATION; COHORT AB Background Cod liver oil is an important source of vitamin D, but also contains other fat-soluble components such as vitamin A. Before 1999, the cod liver oil formula in Norway contained a high concentration of vitamin A (1000 mu g per 5 ml). High vitamin A status is associated with increased risks of several chronic diseases. Objective To investigate the association between cod liver oil intake and asthma development. Methods In the Nord-Trondelag Health Study, a total of 25 616 Norwegian adults aged 19-55 years were followed up from 1995-1997 to 2006-2008. Current analysis based on 17 528 subjects who were free of asthma and had complete information on cod liver oil intake at baseline. Cod liver oil intake was defined as daily intake >= 1 month during the year prior to baseline. Incident asthma was reported as new-onset asthma during the 11-year follow-up. Results Of the 17 528 subjects, 18% (n=3076) consumed cod liver oil daily for >= 1 month over the past year. Cod liver oil intake was significantly associated with incident asthma with an OR of 1.62 (95% CI 1.32 to 1.98) after adjustment for age, sex, daily smoking, physical activity, education, socio-economic status, family history of asthma, and body mass index (BMI). The positive association was consistent across age (<40/>= 40 years), sex (men/women), family history of asthma (yes/no) and BMI subgroups (<25/>= 25 kg/m(2)). Conclusions Intake of cod liver oil with high vitamin A content was significantly associated with increased incidence of adult-onset asthma. C1 [Mai, Xiao-Mei] Norwegian Univ Sci & Technol, Fac Med, Dept Publ Hlth & Gen Practice, N-7491 Trondheim, Norway. [Chen, Yue] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON, Canada. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Mai, XM (reprint author), Norwegian Univ Sci & Technol, Fac Med, Dept Publ Hlth & Gen Practice, N-7491 Trondheim, Norway. EM xiao-mei.mai@ntnu.no FU Research Council of Norway [201895/V50]; AstraZeneca Norway FX This study was supported by the Research Council of Norway (project no. 201895/V50). The Lung Study in HUNT 2 and HUNT 3 received funding from AstraZeneca Norway. None of the funding sources were involved in any aspect of the study design, conduct, analysis, interpretation of data or writing the report. NR 32 TC 9 Z9 9 U1 0 U2 10 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 J9 THORAX JI Thorax PD JAN PY 2013 VL 68 IS 1 BP 25 EP U160 DI 10.1136/thoraxjnl-2012-202061 PG 6 WC Respiratory System SC Respiratory System GA 052NP UT WOS:000312204900006 PM 22977130 ER PT J AU Uthamalingam, S Gurm, GS Ahmado, I Sidhu, MS Flynn, J AF Uthamalingam, Shanmugam Gurm, Gagandeep S. Ahmado, Imad Sidhu, Manavjot S. Flynn, James TI Outcome of Patients With Regadenoson-Induced ST-Segment Depression but Normal Perfusion on Single-Photon Emission Computed Tomography SO ANGIOLOGY LA English DT Article DE regadenoson; single-photon emission computed tomographic myocardial perfusion imaging; ST-segment depression ID ISCHEMIC ELECTROCARDIOGRAPHIC CHANGES; PROGNOSTIC-SIGNIFICANCE; ADENOSINE INFUSION; AGONIST; STRESS; TRIAL AB The prognostic significance of ischemic electrocardiographic (ECG) changes during Regadenoson vasodilator stress in patients with normal single-photon emission computed tomographic myocardial perfusion imaging (SPECT-MPI) is not well described. Of 2473 patients who underwent Regadenoson vasodilator stress testing, 43 (77% women, mean age 72 +/- 10 years) patients were included in the study. During a mean follow-up of 14 +/- 7 months, cardiac death occurred in 1 patient; 5 patients underwent coronary revascularization and none had myocardial infarction. The annual rate of cardiac death and coronary revascularization was 1.9% and 9.9%, respectively. The finding of ischemic ECG changes with normal SPECT-MPI during regadenoson vasodilator stress testing is uncommon, occurs primarily in older women, and is associated with moderately higher subsequent cardiac event rate. C1 [Uthamalingam, Shanmugam; Sidhu, Manavjot S.] Massachusetts Gen Hosp, Dept Cardiovasc Imaging, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Uthamalingam, Shanmugam; Sidhu, Manavjot S.] Harvard Univ, Sch Med, Boston, MA USA. [Uthamalingam, Shanmugam; Ahmado, Imad; Flynn, James] New England Heart Inst, Manchester, NH USA. [Gurm, Gagandeep S.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Sidhu, MS (reprint author), Massachusetts Gen Hosp, Cardiovasc Imaging Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM msidhu1@partners.org NR 15 TC 6 Z9 6 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0003-3197 J9 ANGIOLOGY JI Angiology PD JAN PY 2013 VL 64 IS 1 BP 46 EP 48 DI 10.1177/0003319711436073 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 049TU UT WOS:000312007100008 PM 22323835 ER PT J AU Smith, BN Vaughn, RA Vogt, D King, DW King, LA Shipherd, JC AF Smith, Brian N. Vaughn, Rachel A. Vogt, Dawne King, Daniel W. King, Lynda A. Shipherd, Jillian C. TI Main and interactive effects of social support in predicting mental health symptoms in men and women following military stressor exposure SO ANXIETY STRESS AND COPING LA English DT Article DE social support; resilience; sex differences; stress; mental health; military ID MALE VIETNAM VETERANS; POSTTRAUMATIC-STRESS; RISK-FACTORS; PSYCHOMETRIC PROPERTIES; MULTIDIMENSIONAL SCALE; PTSD CHECKLIST; LIFE EVENTS; DISORDER; COMBAT; AFGHANISTAN AB Evidence across a multitude of contexts indicates that social support is associated with reduced risk for mental health symptoms. More information is needed on the effectiveness of different sources of support, as well as sex differences in support. Associations between social support from two sources the military unit and friends and family and mental health symptoms were examined in a study of 1571 Marine recruits assessed at the beginning and end of a highly stressful 13-week training program. Military social support buffered the stressor exposureposttraumatic stress symptomatology (PTSS) relationship, whereas the relationship between stressor exposure and PTSS was highest when civilian social support was high. Further inspection of the interactions revealed that military support was most important at high levels of stressor exposure. Sex differences in the relationship between social support and symptoms were found, such that support from military peers was associated with lower levels of PTSS for men, whereas civilian support was associated with lower PTSS for women. While civilian social support was associated with lower levels of depression symptom severity in both women and men, the relationship was stronger for women. Reviewed implications focus on the importance of considering the recipient, source, and context of social support. C1 [Smith, Brian N.; Vaughn, Rachel A.; Vogt, Dawne; King, Lynda A.; Shipherd, Jillian C.] VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA. [Smith, Brian N.; Vogt, Dawne; Shipherd, Jillian C.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [King, Daniel W.; King, Lynda A.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [King, Daniel W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA USA. RP Smith, BN (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, 150 S Huntington Ave,116B-3, Boston, MA 02130 USA. EM Brian.Smith12@va.gov NR 43 TC 15 Z9 17 U1 7 U2 36 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1061-5806 J9 ANXIETY STRESS COPIN JI Anxiety Stress Coping PD JAN 1 PY 2013 VL 26 IS 1 BP 52 EP 69 DI 10.1080/10615806.2011.634001 PG 18 WC Neurosciences; Psychiatry; Psychology, Multidisciplinary SC Neurosciences & Neurology; Psychiatry; Psychology GA 051KH UT WOS:000312124700004 PM 22098413 ER PT J AU Van Dam, NT Gros, DF Earleywine, M Antony, MM AF Van Dam, Nicholas T. Gros, Daniel F. Earleywine, Mitch Antony, Martin M. TI Establishing a trait anxiety threshold that signals likelihood of anxiety disorders SO ANXIETY STRESS AND COPING LA English DT Article DE state trait inventory for cognitive and somatic anxiety; STICSA; anxiety; assessment; cut-off score ID STRESS SCALES DASS; PSYCHOMETRIC PROPERTIES; GENERAL-POPULATION; MENTAL-ILLNESS; DEPRESSION; INVENTORY; STATE; PREVALENCE; DIMENSIONS; RELIABILITY AB Evidence suggests that the State Trait Inventory for Cognitive and Somatic Anxiety (STICSA) may be a more pure measure of anxiety than other commonly used scales. Further, the STICSA has excellent psychometric properties in both clinical and nonclinical samples. The present study aimed to extend the utility of the STICSA Trait version by identifying a cut-off score that could differentiate a group of clinically diagnosed anxiety disorder patients (n=398) from a group of student controls (n =439). Two receiver operating characteristic curve analyses indicated cut-off scores of 43 (sensitivity=.73, specificity=.74, classification accuracy=.74) and 40 (sensitivity=.80, specificity=.67, classification accuracy=.73), respectively. In a large community sample (n =6685), a score of 43 identified 11.5% of individuals as probable cases of clinical anxiety, while a score of 40 identified 17.0% of individuals as probable cases of clinical anxiety. As a result of differences in sensitivity and specificity, the present findings suggest a cut-off score of 43 is optimal to identify probable cases of clinical anxiety, while a cut-off score of 40 is optimal to screen for the possible presence of anxiety disorders. C1 [Van Dam, Nicholas T.; Earleywine, Mitch] SUNY Albany, Dept Psychol, Albany, NY 12222 USA. [Gros, Daniel F.] Ralph H Johnson VAMC, Mental Hlth Serv, Charleston, SC USA. [Gros, Daniel F.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Antony, Martin M.] Ryerson Univ, Dept Psychol, Toronto, ON, Canada. [Antony, Martin M.] St Josephs Healthcare, Anxiety Treatment & Res Ctr, Hamilton, ON, Canada. RP Van Dam, NT (reprint author), SUNY Albany, Dept Psychol, 1400 Washington Ave, Albany, NY 12222 USA. EM ntvandam@gmail.com OI Van Dam, Nicholas/0000-0002-1131-0739 NR 46 TC 16 Z9 16 U1 2 U2 13 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1061-5806 J9 ANXIETY STRESS COPIN JI Anxiety Stress Coping PD JAN 1 PY 2013 VL 26 IS 1 BP 70 EP 86 DI 10.1080/10615806.2011.631525 PG 17 WC Neurosciences; Psychiatry; Psychology, Multidisciplinary SC Neurosciences & Neurology; Psychiatry; Psychology GA 051KH UT WOS:000312124700005 PM 22091946 ER PT J AU DeGutis, J Wilmer, J Mercado, RJ Cohan, S AF DeGutis, Joseph Wilmer, Jeremy Mercado, Rogelio J. Cohan, Sarah TI Using regression to measure holistic face processing reveals a strong link with face recognition ability SO COGNITION LA English DT Article DE Face recognition; Face perception; Holistic processing; Individual differences; Composite task; Part-whole task ID OWN-RACE; DEVELOPMENTAL PROSOPAGNOSIA; INDIVIDUAL-DIFFERENCES; MEMORY TEST; PERCEPTION; INFORMATION; ADVANTAGE; ACCOUNT; PARTS AB Although holistic processing is thought to underlie normal face recognition ability, widely discrepant reports have recently emerged about this link in an individual differences context. Progress in this domain may have been impeded by the widespread use of subtraction scores, which lack validity due to their contamination with control condition variance. Regressing, rather than subtracting, a control condition from a condition of interest corrects this validity problem by statistically removing all control condition variance, thereby producing a specific measure that is uncorrelated with the control measure. Using 43 participants, we measured the relationships amongst the Cambridge Face Memory Test (CFMT) and two holistic processing measures, the composite task (CT) and the part-whole task (PW). For the holistic processing measures (CT and PW), we contrasted the results for regressing vs. subtracting the control conditions (parts for PW; misaligned congruency effect for CT) from the conditions of interest (wholes for PW; aligned congruency effect for CT). The regression-based holistic processing measures correlated with each other and with CFMT, supporting the idea of a unitary holistic processing mechanism that is involved in skilled face recognition. Subtraction scores yielded weaker correlations, especially for the PW. Together, the regression-based holistic processing measures predicted more than twice the amount of variance in CFMT (R-2 = .21) than their respective subtraction measures (R-2 = .10). We conclude that holistic processing is robustly linked to skilled face recognition. In addition to confirming this theoretically significant link, these results provide a case in point for the inappropriateness of subtraction scores when requiring a specific individual differences measure that removes the variance of a control task. Published by Elsevier B.V. C1 [DeGutis, Joseph; Mercado, Rogelio J.] VA Boston Healthcare Syst, GRECC, Boston, MA 02130 USA. [DeGutis, Joseph; Mercado, Rogelio J.; Cohan, Sarah] Harvard Univ, Dept Psychol, Vis Sci Lab, Cambridge, MA 02138 USA. [Wilmer, Jeremy] Wellesley Univ, Dept Psychol, Wellesley, MA USA. RP DeGutis, J (reprint author), VA Boston Healthcare Syst, GRECC, 150 S Huntington Ave, Boston, MA 02130 USA. EM degutis@wjh.harvard.edu NR 47 TC 66 Z9 66 U1 1 U2 38 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0010-0277 J9 COGNITION JI Cognition PD JAN PY 2013 VL 126 IS 1 BP 87 EP 100 DI 10.1016/j.cognition.2012.09.004 PG 14 WC Psychology, Experimental SC Psychology GA 052DH UT WOS:000312177400006 PM 23084178 ER PT J AU Hirata, A Utikal, J Yamashita, S Aoki, H Watanabe, A Yamamoto, T Okano, H Bardeesy, N Kunisada, T Ushijima, T Hara, A Jaenisch, R Hochedlinger, K Yamada, Y AF Hirata, Akihiro Utikal, Jochen Yamashita, Satoshi Aoki, Hitomi Watanabe, Akira Yamamoto, Takuya Okano, Hideyuki Bardeesy, Nabeel Kunisada, Takahiro Ushijima, Toshikazu Hara, Akira Jaenisch, Rudolf Hochedlinger, Konrad Yamada, Yasuhiro TI Dose-dependent roles for canonical Wnt signalling in de novo crypt formation and cell cycle properties of the colonic epithelium SO DEVELOPMENT LA English DT Article DE Wnt signalling; Notch signalling; Intestinal stem cell; Mouse ID INTESTINAL STEM-CELLS; BETA-CATENIN; COLORECTAL-CANCER; PROGENITOR CELLS; IN-VIVO; WNT/BETA-CATENIN; MICE; APC; PROLIFERATION; DIFFERENTIATION AB There is a gradient of beta-catenin expression along the colonic crypt axis with the highest levels at the crypt bottom. In addition, colorectal cancers show a heterogeneous subcellular pattern of beta-catenin accumulation. However, it remains unclear whether different levels of Wnt signalling exert distinct roles in the colonic epithelium. Here, we investigated the dose-dependent effect of canonical Wnt activation on colonic epithelial differentiation by controlling the expression levels of stabilised beta-catenin using a doxycycline-inducible transgenic system in mice. We show that elevated levels of Wnt signalling induce the amplification of Lgr5+ cells, which is accompanied by crypt fission and a reduction in cell proliferation among progenitor cells. By contrast, lower levels of beta-catenin induction enhance cell proliferation rates of epithelial progenitors without affecting crypt fission rates. Notably, slow-cycling cells produced by beta-catenin activation exhibit activation of Notch signalling. Consistent with the interpretation that the combination of Notch and Wnt signalling maintains crypt cells in a low proliferative state, the treatment of beta-catenin-expressing mice with a Notch inhibitor turned such slow-cycling cells into actively proliferating cells. Our results indicate that the activation of the canonical Wnt signalling pathway is sufficient for de novo crypt formation, and suggest that different levels of canonical Wnt activations, in cooperation with Notch signalling, establish a hierarchy of slower-cycling stem cells and faster-cycling progenitor cells characteristic for the colonic epithelium. C1 [Utikal, Jochen; Bardeesy, Nabeel; Hochedlinger, Konrad] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Stem Cell Inst, Boston, MA 02114 USA. [Hirata, Akihiro] Gifu Univ, Life Sci Res Ctr, Div Anim Expt, Gifu 5011194, Japan. [Utikal, Jochen; Bardeesy, Nabeel; Hochedlinger, Konrad] Harvard Univ, Stem Cell Inst, Ctr Regenerat Med, Boston, MA 02114 USA. [Utikal, Jochen] German Canc Res Ctr, Skin Canc Unit, D-6900 Heidelberg, Germany. [Utikal, Jochen] Heidelberg Univ, Univ Med Ctr Mannheim, Dept Dermatol Venereol & Allergol, D-6800 Mannheim, Germany. [Yamashita, Satoshi; Ushijima, Toshikazu] Natl Canc Ctr, Res Inst, Div Epigen, Chuo Ku, Tokyo 104, Japan. [Aoki, Hitomi; Kunisada, Takahiro] Gifu Univ, Grad Sch Med, Dept Tissue & Organ Dev, Gifu 5011194, Japan. [Hara, Akira] Gifu Univ, Grad Sch Med, Dept Tumor Pathol, Gifu 5011194, Japan. [Watanabe, Akira; Yamamoto, Takuya; Yamada, Yasuhiro] Kyoto Univ, Ctr iPS Cell Res & Applicat CiRA, Inst Integrated Cell Mat Sci WPI iCeMS, Sakyo Ku, Kyoto 6068507, Japan. [Okano, Hideyuki] Keio Univ, Sch Med, Dept Physiol, Shinjuku Ku, Tokyo 1608582, Japan. [Jaenisch, Rudolf] MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Yamada, Yasuhiro] Japan Sci & Technol Agcy, PRESTO, Saitama, Japan. RP Hochedlinger, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Stem Cell Inst, 185 Cambridge St, Boston, MA 02114 USA. EM khochedlinger@helix.mgh.harvard.edu; y-yamada@cira.kyoto-u.ac.jp RI Hidokano, Hideyuki/J-5973-2013; OI Kunisada, Takahiro/0000-0003-1651-2716; Utikal, Jochen/0000-0001-5316-0241 FU PRESTO; Ministry of Health, Labour and Welfare of Japan; Ministry of Education, Culture, Sports, Science and Technology of Japan; German Cancer Aid; German Research Council [SFB873]; National Institutes of Health [DP2OD003266, R01HD058013] FX This study is supported by PRESTO, Grants-in-Aid from the Ministry of Health, Labour and Welfare of Japan, and Ministry of Education, Culture, Sports, Science and Technology of Japan [Y.Y.]. J.U. is supported by grants of the German Cancer Aid and German Research Council [SFB873]. K. H. was supported by the National Institutes of Health [DP2OD003266 and R01HD058013]. Deposited in PMC for release after 12 months. NR 45 TC 30 Z9 30 U1 0 U2 13 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 JAN 1 PY 2013 VL 140 IS 1 BP 66 EP 75 DI 10.1242/dev.084103 PG 10 WC Developmental Biology SC Developmental Biology GA 048ZA UT WOS:000311950600008 PM 23222438 ER PT J AU Dougherty, M Kamel, G Grimaldi, M Gfrerer, L Shubinets, V Ethier, R Hickey, G Cornell, RA Liao, EC AF Dougherty, Max Kamel, George Grimaldi, Michael Gfrerer, Lisa Shubinets, Valeriy Ethier, Renee Hickey, Graham Cornell, Robert A. Liao, Eric C. TI Distinct requirements for wnt9a and irf6 in extension and integration mechanisms during zebrafish palate morphogenesis SO DEVELOPMENT LA English DT Article DE Palate; irf6; wnt9a; Cranial neural crest; Craniofacial; Zebrafish ID POPLITEAL PTERYGIUM SYNDROMES; CLEFT-PALATE; MOLECULAR-MECHANISMS; LIP; EXPRESSION; GENE; WOUDE; VAN; PALATOGENESIS; SPECIFICATION AB Development of the palate in vertebrates involves cranial neural crest migration, convergence of facial prominences and extension of the cartilaginous framework. Dysregulation of palatogenesis results in orofacial clefts, which represent the most common structural birth defects. Detailed analysis of zebrafish palatogenesis revealed distinct mechanisms of palatal morphogenesis: extension, proliferation and integration. We show that wnt9a is required for palatal extension, wherein the chondrocytes form a proliferative front, undergo morphological change and intercalate to form the ethmoid plate. Meanwhile, irf6 is required specifically for integration of facial prominences along a V-shaped seam. This work presents a mechanistic analysis of palate morphogenesis in a clinically relevant context. C1 [Dougherty, Max; Kamel, George; Grimaldi, Michael; Gfrerer, Lisa; Shubinets, Valeriy; Ethier, Renee; Hickey, Graham; Liao, Eric C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA. [Dougherty, Max; Kamel, George; Grimaldi, Michael; Gfrerer, Lisa; Shubinets, Valeriy; Ethier, Renee; Hickey, Graham; Liao, Eric C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. [Cornell, Robert A.] Univ Iowa, Carver Coll Med, Dept Anat & Cell Biol, Iowa City, IA 52242 USA. [Liao, Eric C.] Harvard Univ, Stem Cell Inst, Boston, MA 02114 USA. RP Liao, EC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA. EM cliao@partners.org OI Cornell, Robert/0000-0003-4207-9100 FU March of Dimes Basil O'Connor Starter Scholar Award; Shriners Hospital for Children; American Surgical Association; Plastic Surgery Foundation; Howard Hughes Medical Institute FX E.C.L. received generous support from the March of Dimes Basil O'Connor Starter Scholar Award, from Shriners Hospital for Children, from the American Surgical Association and from the Plastic Surgery Foundation. G. K. was supported by the Plastic Surgery Foundation. V. S. was supported by Howard Hughes Medical Institute Medical Student Research Award. NR 40 TC 18 Z9 18 U1 1 U2 14 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JAN 1 PY 2013 VL 140 IS 1 BP 76 EP 81 DI 10.1242/dev.080473 PG 6 WC Developmental Biology SC Developmental Biology GA 048ZA UT WOS:000311950600009 PM 23154410 ER PT J AU Mirzakhani, H Eikermann, M AF Mirzakhani, Hooman Eikermann, Matthias TI Train-of-four recovery does not indicate optimal recovery of the margin of safety of neuromuscular transmission SO EUROPEAN JOURNAL OF ANAESTHESIOLOGY LA English DT Letter ID BLOCKADE; PHARYNGEAL; FADE C1 [Eikermann, Matthias] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Crit Care Div, Boston, MA 02114 USA. RP Eikermann, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Crit Care Div, Boston, MA 02114 USA. EM meikermann@partners.org OI Mirzakhani, Hooman/0000-0002-2290-4436 NR 8 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0265-0215 J9 EUR J ANAESTH JI Eur. J. Anaesth. PD JAN PY 2013 VL 30 IS 1 BP 40 EP 41 DI 10.1097/EJA.0b013e328356bc24 PG 2 WC Anesthesiology SC Anesthesiology GA 049UB UT WOS:000312007800010 PM 22801583 ER PT J AU Gakis, G Efstathiou, J Lerner, SP Cookson, MS Keegan, KA Guru, KA Shipley, WU Heidenreich, A Schoenberg, MP Sagaloswky, AI Soloway, MS Stenzl, A AF Gakis, Georgios Efstathiou, Jason Lerner, Seth P. Cookson, Michael S. Keegan, Kirk A. Guru, Khurshid A. Shipley, William U. Heidenreich, Axel Schoenberg, Mark P. Sagaloswky, Arthur I. Soloway, Mark S. Stenzl, Arnulf TI ICUD-EAU International Consultation on Bladder Cancer 2012: Radical Cystectomy and Bladder Preservation for Muscle-Invasive Urothelial Carcinoma of the Bladder SO EUROPEAN UROLOGY LA English DT Review DE Bladder cancer; Radical cystectomy; Bladder preservation; Recommendations; Guidelines ID TRANSITIONAL-CELL CARCINOMA; EXTENDED PELVIC LYMPHADENECTOMY; ORTHOTOPIC URINARY-DIVERSION; LYMPH-NODE METASTASIS; QUALITY-OF-LIFE; URETHRAL RECURRENCE; TRANSURETHRAL RESECTION; CONTEMPORARY SERIES; CENTER EXPERIENCE; RISK-FACTORS AB Context: New guidelines of the International Consultation on Urological Diseases for the treatment of muscle-invasive bladder cancer (MIBC) have recently been published. Objective: To provide a comprehensive overview of the current role of radical cystectomy (RC) in MIBC. Evidence acquisition: A detailed Medline analysis was performed for original articles addressing the role of RC with regard to indication, timing, surgical extent, perioperative morbidity, oncologic outcome, and follow-up. The analysis also included radiation-based bladder-preserving strategies. Evidence synthesis: The major findings are presented in an evidence-based fashion and are based on large retrospective unicenter and multicenter series with some prospective data. Conclusions: Open RC is the standard treatment for locoregional control of MIBC. Delay of RC is associated with reduced cancer-specific survival. In males, standard RC includes the removal of the bladder, prostate, seminal vesicles, and distal ureters; in females, RC includes an anterior pelvic exenteration including the bladder, entire urethra and adjacent vagina, uterus, and distal ureters. A procedure sparing the urethra and the urethra-supplying autonomous nerves can be performed in case of a planned orthotopic neobladder. Further technical variations (ie, seminal-sparing or vaginal-sparing techniques) aimed at improving functional outcomes must be weighed against the risk of a positive margin. Laparoscopic surgery is promising, but long-term data are required prior to accepting it as an option equivalent to the open procedure. Lymphadenectomy should remove all lymphatic tissue around the common iliac, external iliac, internal iliac, and obturator region bilaterally. Complications after RC should be reported according to the modified Clavien grading system. In selected patients with MIBC, bladder-preserving therapy with cystectomy reserved for tumor recurrence represents a safe and effective alternative to immediate RC. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved. C1 [Gakis, Georgios; Stenzl, Arnulf] Univ Tubingen, Dept Urol, Univ Hosp Tuebingen, D-72076 Tubingen, Germany. [Efstathiou, Jason; Shipley, William U.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Lerner, Seth P.] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. [Cookson, Michael S.; Keegan, Kirk A.] Vanderbilt Univ, Med Ctr, Dept Urol Surg, Nashville, TN USA. [Guru, Khurshid A.] Roswell Pk Canc Inst, Dept Urol, Buffalo, NY 14263 USA. [Heidenreich, Axel] Rhein Westfal TH Aachen, Dept Urol, Univ Hosp Aachen, Aachen, Germany. [Schoenberg, Mark P.] Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA. [Sagaloswky, Arthur I.] Univ Texas SW Med Ctr Dallas, Dept Urol, Dallas, TX 75390 USA. [Soloway, Mark S.] Univ Miami, Miller Sch Med, Dept Urol, Miami, FL 33136 USA. RP Gakis, G (reprint author), Univ Tubingen, Dept Urol, Univ Hosp Tuebingen, Hoppe Seyler Str 3, D-72076 Tubingen, Germany. EM georgios.gakis@med.uni-tuebingen.de NR 106 TC 119 Z9 124 U1 1 U2 19 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD JAN PY 2013 VL 63 IS 1 BP 45 EP 57 DI 10.1016/j.eururo.2012.08.009 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA 049SQ UT WOS:000312004100011 PM 22917985 ER PT J AU Efstathiou, JA Shipley, WU AF Efstathiou, Jason A. Shipley, William U. TI Re: Radiotherapy with or without Chemotherapy in Muscle-invasive Bladder Cancer SO EUROPEAN UROLOGY LA English DT Editorial Material ID CISPLATIN C1 [Efstathiou, Jason A.; Shipley, William U.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Efstathiou, JA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM jefstathiou@partners.org NR 5 TC 5 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD JAN PY 2013 VL 63 IS 1 BP 181 EP 182 DI 10.1016/j.eururo.2012.10.032 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 049SQ UT WOS:000312004100036 PM 23218494 ER PT J AU Dretler, SP Eisner, BH AF Dretler, Stephen P. Eisner, Brian H. TI Re: Ureteroscopic Treatment of Patients with Small, Painful, Non-obstructing Renal Stones: The Small Stone Syndrome SO EUROPEAN UROLOGY LA English DT Editorial Material C1 [Dretler, Stephen P.; Eisner, Brian H.] Harvard Univ, Dept Urol, Kidney Stone Ctr, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. RP Eisner, BH (reprint author), Harvard Univ, Dept Urol, Kidney Stone Ctr, Massachusetts Gen Hosp,Med Sch, GRB 1102,55 Fruit St, Boston, MA 02114 USA. EM beisner@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD JAN PY 2013 VL 63 IS 1 BP 182 EP 182 DI 10.1016/j.eururo.2012.10.033 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 049SQ UT WOS:000312004100037 PM 23218495 ER PT J AU Morgan, DJ Pineles, L Shardell, M Graham, MM Mohammadi, S Forrest, GN Reisinger, HS Schweizer, ML Perencevich, EN AF Morgan, Daniel J. Pineles, Lisa Shardell, Michelle Graham, Margaret M. Mohammadi, Shahrzad Forrest, Graeme N. Reisinger, Heather S. Schweizer, Marin L. Perencevich, Eli N. TI The Effect of Contact Precautions on Healthcare Worker Activity in Acute Care Hospitals SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID INFECTION-CONTROL; TRANSMISSION; ASSOCIATION; GLOVE; HAND AB BACKGROUND AND OBJECTIVE. Contact precautions are a cornerstone of infection prevention but have also been associated with less healthcare worker (HCW) contact and adverse events. We studied how contact precautions modified HCW behavior in 4 acute care facilities. DESIGN. Prospective cohort study. PARTICIPANTS AND SETTING. Four acute care facilities in the United States performing active surveillance for methicillin-resistant Staphylococcus aureus. METHODS. Trained observers performed "secret shopper" monitoring of HCW activities during routine care, using a standardized collection tool and fixed 1-hour observation periods. RESULTS. A total of 7,743 HCW visits were observed over 1,989 hours. Patients on contact precautions had 36.4% fewer hourly HCW visits than patients not on contact precautions (2.78 vs 4.37 visits per hour; P < .001) as well as 17.7% less direct patient contact time with HCWs (13.98 vs 16.98 minutes per hour; P = .02). Patients on contact precautions tended to have fewer visitors (23.6% fewer; P = .08). HCWs were more likely to perform hand hygiene on exiting the room of a patient on contact precautions (63.2% vs 47.4% in rooms of patients not on contact precautions; P<.001). CONCLUSION. Contact precautions were found to be associated with activities likely to reduce transmission of resistant pathogens, such as fewer visits and better hand hygiene at exit, while exposing patients on contact precautions to less HCW contact, less visitor contact, and potentially other unintended outcomes. Infect Control Hosp Epidemiol 2013;34(1):69-73 C1 [Morgan, Daniel J.; Pineles, Lisa; Shardell, Michelle] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Morgan, Daniel J.; Pineles, Lisa] Vet Affairs Maryland Hlth Care Syst, Baltimore, MD USA. [Graham, Margaret M.; Reisinger, Heather S.; Schweizer, Marin L.; Perencevich, Eli N.] Univ Iowa, Carver Coll Med, Iowa City, IA USA. [Mohammadi, Shahrzad; Forrest, Graeme N.] Portland VA Med Ctr, Portland, OR USA. [Reisinger, Heather S.; Perencevich, Eli N.] Iowa City Vet Affairs Hlth Care Syst, Iowa City, IA USA. RP Morgan, DJ (reprint author), 685 W Baltimore St,MSTF 334D, Baltimore, MD 21201 USA. EM dmorgan@epi.umaryland.edu FU Veterans Affairs Health Services Research and Development Investigator Initiated Research [09-099]; Association of American Medical Colleges/Centers for Disease Control and Prevention [CCU319276]; Agency for Healthcare Research and Quality [K08-HS18111]; Merck FX Veterans Affairs Health Services Research and Development Investigator Initiated Research 09-099 (E.N.P.); Association of American Medical Colleges/Centers for Disease Control and Prevention CCU319276 (E.N.P., D.J.M.); and Agency for Healthcare Research and Quality K08-HS18111 (D.J.M.).; D.J.M. reports that he has received an unrestricted research grant from Merck. All other authors report no conflicts of interest relevant to this article. All authors submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest, and the conflicts that the editors consider relevant to this article are disclosed here. NR 20 TC 41 Z9 42 U1 1 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD JAN PY 2013 VL 34 IS 1 BP 69 EP 73 DI 10.1086/668775 PG 5 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 049YC UT WOS:000312018300010 PM 23221195 ER PT J AU Fukuta, Y Muder, RR AF Fukuta, Yuriko Muder, Robert R. TI Infections in Psychiatric Facilities, with an Emphasis on Outbreaks SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Review ID A STREPTOCOCCAL DISEASE; INTESTINAL PARASITIC INFECTIONS; RESISTANT STAPHYLOCOCCUS-AUREUS; HUMAN METAPNEUMOVIRUS INFECTION; TERM-CARE FACILITY; HEPATITIS-A; NOROVIRUS OUTBREAK; INFLUENZA OUTBREAK; INSTITUTION; EPIDEMIOLOGY AB Outbreaks of infectious diseases in psychiatric units are very different from those in intensive care units or acute medical-surgical units. Outbreaks in psychiatric units are most often caused by agents circulating in the community. Infection control in psychiatric units also faces unique challenges due to the characteristics of the patients and facilities. Infect Control Hosp Epidemiol 2013;34(1):80-88 C1 [Muder, Robert R.] VA Pittsburgh Healthcare Syst, Infect Dis Sect, Pittsburgh, PA 15240 USA. [Fukuta, Yuriko; Muder, Robert R.] Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA USA. RP Muder, RR (reprint author), VA Pittsburgh Healthcare Syst, Infect Dis Sect, Univ Dr C, Pittsburgh, PA 15240 USA. EM robert.muder@va.gov NR 52 TC 4 Z9 4 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD JAN PY 2013 VL 34 IS 1 BP 80 EP 88 DI 10.1086/668774 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 049YC UT WOS:000312018300012 PM 23221197 ER PT J AU Reardon, JM Valenzuela, JE Parmar, S Venkatesh, AK Schuur, JD Allen, MB Pallin, DJ AF Reardon, Joseph M. Valenzuela, Josephine E. Parmar, Siddharth Venkatesh, Arjun K. Schuur, Jeremiah D. Allen, Matthew B. Pallin, Daniel J. TI The Time Burden of Alcohol-Based Hand Cleanser When Using Nonsterile Gloves SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID CARE-ASSOCIATED INFECTIONS; EMERGENCY; HYGIENE AB We quantified the time burden of alcohol-based handrub accompanying nonsterile-glove use among emergency physicians, through observation in controlled and clinical settings. We report gloving episodes per hour, gloving times with and without handrub, and handrub recommendations compliance. Handrub adds 46 seconds to each glove-use episode, and we provide national extrapolations. Infect Control Hosp Epidemiol 2013;34(1):96-98 C1 [Valenzuela, Josephine E.; Schuur, Jeremiah D.; Allen, Matthew B.; Pallin, Daniel J.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Reardon, Joseph M.; Valenzuela, Josephine E.] Harvard Univ, Sch Med, Boston, MA USA. [Venkatesh, Arjun K.] Brigham & Womens Hosp Massachusetts Gen Hosp Harv, Boston, MA USA. [Pallin, Daniel J.] Childrens Hosp, Div Emergency Med, Boston, MA 02115 USA. RP Pallin, DJ (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. EM dpallin@partners.org RI Pallin, Daniel/H-6382-2013; Reardon, Joseph/I-4419-2012 OI Pallin, Daniel/0000-0002-8517-9702; Reardon, Joseph/0000-0002-1093-5518 FU Harvard Medical School; Agency for Healthcare Research and Quality [R18-HS020013]; Johnson Johnson FX This work was supported by a Scholarship in Medicine grant from Harvard Medical School to J.E.V. J.D.S.'s time is supported by a grant from the Agency for Healthcare Research and Quality (R18-HS020013).; J.M.R. reports that he received a scholarship in 2010 from Johnson & Johnson, which previously manufactured Purell handrub. All other authors report no conflicts of interest relevant to this article. All authors submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest, and the conflicts that the editors consider relevant to this article are disclosed here. NR 10 TC 3 Z9 3 U1 0 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD JAN PY 2013 VL 34 IS 1 BP 96 EP 98 DI 10.1086/668781 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 049YC UT WOS:000312018300015 PM 23221200 ER PT J AU Sanchez-Villegas, A Field, AE O'Reilly, EJ Fava, M Gortmaker, S Kawachi, I Ascherio, A AF Sanchez-Villegas, Almudena Field, Alison E. O'Reilly, Eilis J. Fava, Maurizio Gortmaker, Steven Kawachi, Ichiro Ascherio, Alberto TI Perceived and actual obesity in childhood and adolescence and risk of adult depression SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article ID C-REACTIVE PROTEIN; BODY-MASS INDEX; SELF-ESTEEM; BIRTH COHORT; SOCIOECONOMIC POSITION; CARDIOVASCULAR-DISEASE; OVERWEIGHT CHILDREN; MAJOR DEPRESSION; YOUNG ADULTHOOD; SWEDISH MEN AB Background Obesity in childhood and adolescence has important health consequences, but its relation to risk of adult depression remains uncertain. Objective To examine the effect of perceived and actual obesity during childhood and adolescence on prevalence and incidence of adult depression risk. Methods Cohort study of 91 798 female registered nurses followed longitudinally for 12 years. Results As compared with lean women of the same age, women in the two highest categories of body shape at age 10 had both higher prevalence (OR = 2.59, 95% CI 1.46 to 4.61) and incidence (OR = 2.01, 95% CI 1.08 to 3.71) of depression. Similar results were obtained for body shape at age 20 (OR = 3.43 for prevalence and OR = 2.03 for incidence) and for body mass index (BMI) at age 18 (OR = 2.92 for BMI >= 40 kg/m(2)). These associations remained significant after adjustment for multiple confounders. Conclusion These results indicate that childhoodeadolescence obesity is a strong and independent risk factor for adult depression. C1 [Sanchez-Villegas, Almudena] Univ Las Palmas Gran Canaria, Dept Clin Sci, Las Palmas Gran Canaria 35008, Spain. [Sanchez-Villegas, Almudena] Univ Navarra, Dept Prevent Med & Publ Hlth, E-31080 Pamplona, Spain. [Field, Alison E.] Childrens Hosp Boston, Dept Med, Div Adolescent Young Adult Med, Boston, MA USA. [Field, Alison E.; Kawachi, Ichiro] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [O'Reilly, Eilis J.; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [O'Reilly, Eilis J.; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Fava, Maurizio] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat Depress Clin & Res Program, Boston, MA USA. [Gortmaker, Steven; Kawachi, Ichiro] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Sanchez-Villegas, A (reprint author), Univ Las Palmas Gran Canaria, Dept Clin Sci, POB 550, Las Palmas Gran Canaria 35008, Spain. EM asanchez@dcc.ulpgc.es FU National Association for Research on Schizophrenia and Depression; Spanish Ministry of Education [PR2004-0475] FX AA is the recipient of an Independent Investigator Award from the National Association for Research on Schizophrenia and Depression that contributed in part to funding of this project. The Spanish Ministry of Education granted AS-V with a 6-month stay at Harvard University (PR2004-0475). The funding sources had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report and in the decision to submit the paper for publication. NR 53 TC 11 Z9 11 U1 1 U2 22 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD JAN PY 2013 VL 67 IS 1 BP 81 EP 86 DI 10.1136/jech-2012-201435 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 049DJ UT WOS:000311961900014 PM 22766776 ER PT J AU Patrician, PA Dolansky, MA Pair, V Bates, M Moore, SM Splaine, M Gilman, SC AF Patrician, Patricia A. Dolansky, Mary A. Pair, Vincent Bates, Mekeshia Moore, Shirley M. Splaine, Mark Gilman, Stuart C. TI The Veterans Affairs National Quality Scholars Program A Model for Interprofessional Education in Quality and Safety SO JOURNAL OF NURSING CARE QUALITY LA English DT Article DE interprofessional education; patient safety; program development; quality improvement; Quality and Safety Education for Nurses AB The Quality and Safety Education for Nurses (QSEN) project is enhancing the emphasis on quality care and patient safety content in nursing schools. A partnership between QSEN and the Veterans Affairs National Quality Scholars program resulted in a unique experiential, interdisciplinary fellowship for both nurses and physicians. This article introduces the Veterans Affairs National Quality Scholars program and provides examples of learning activities and fellows' accomplishments. Interprofessional quality and safety education at the doctoral and postdoctoral levels is germane to improving the quality of health care. C1 [Patrician, Patricia A.] Univ Alabama Birmingham, Sch Nursing, Birmingham, AL 35294 USA. [Patrician, Patricia A.; Pair, Vincent] Birmingham VA Med Ctr, VA Natl Qual Scholars Program, Birmingham, AL USA. [Dolansky, Mary A.; Moore, Shirley M.] Case Western Reserve Univ, Frances Payne Bolton Sch Nursing, Cleveland, OH 44106 USA. [Dolansky, Mary A.] Cleveland VA Med Ctr, VA Natl Qual Scholars Program, Cleveland, OH USA. [Bates, Mekeshia] US PHS, Arlington, VA USA. [Splaine, Mark] Dartmouth Inst Hlth Policy & Clin Practice, Ctr Leadership & Improvement, Lebanon, NH USA. [Splaine, Mark] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. [Gilman, Stuart C.] Vet Hlth Adm, Off Acad Affiliat, US Dept Vet Affairs, Washington, DC USA. RP Patrician, PA (reprint author), Univ Alabama Birmingham, Sch Nursing, NB 324,1720 2nd Ave S, Birmingham, AL 35294 USA. EM ppatrici@uab.edu FU Veterans Affairs Office of Academic Affiliations, Washington, DC; VAQS Fellowship; VA; QSEN/Robert Wood Johnson Foundation; Quality and Safety Education for Nurses (QSEN) initiative; Robert Wood Johnson Foundation FX The Veterans Affairs National Quality Scholars Program is supported by the Veterans Affairs Office of Academic Affiliations, Washington, DC. Support for the Senior Nursing Scholars is currently provided by the Quality and Safety Education for Nurses (QSEN) initiative funded by the Robert Wood Johnson Foundation. The authors thank Anna Alt-White, PhD, RN; Linda Cronenwett, PhD, RN, FAAN; Mary Dougherty, PhD, RN; and Cathy Rick, RN, NEA-BC, FACHE, FAAN.; All authors are (or were) affiliated with the VAQS Fellowship and funded, at least in part, through either the VA (Pair, Bates, Gilman, and Splaine) or QSEN/Robert Wood Johnson Foundation (Patrician, Dolansky, and Moore). NR 15 TC 3 Z9 3 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1057-3631 J9 J NURS CARE QUAL JI J. Nurs. Care Qual. PD JAN-MAR PY 2013 VL 28 IS 1 BP 24 EP 32 DI 10.1097/NCQ.0b013e3182678f41 PG 9 WC Nursing SC Nursing GA 050QI UT WOS:000312068700005 PM 22868564 ER PT J AU Oral, E Neils, AL Lyons, C Fung, M Doshi, B Muratoglu, OK AF Oral, Ebru Neils, Andrew L. Lyons, Chelsea Fung, Mitchell Doshi, Brinda Muratoglu, Orhun K. TI y Surface cross-linked UHMWPE can enable the use of larger femoral heads in total joints SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE wear; fatigue; impact resistant; antioxidant; joint arthroplasty ID MOLECULAR-WEIGHT POLYETHYLENE; TOTAL HIP-ARTHROPLASTY; VITAMIN-E; ALPHA-TOCOPHEROL; PROPAGATION RESISTANCE; IRRADIATED UHMWPE; WEAR-RESISTANCE; REPLACEMENTS; RADIATION; LINKING AB Limiting cross-linking to the articular surfaces of ultrahigh molecular weight polyethylene (UHMWPE) to increase wear resistance while preventing detrimental effects of cross-linking on mechanical strength has been a desirable goal. A surface cross-linked UHMWPE can be achieved by blending UHMWPE with a free radical scavenger, such as vitamin E, consolidating the blend into an implant shape, extracting the vitamin E from the surface, and radiation cross-linking the surface extracted blend. This process results in high cross-link density in the vitamin E-depleted surface region because vitamin E hinders cross-linking during irradiation. In this study, we described the properties of successful extraction media and the manipulation of the wear and mechanical properties of extracted, irradiated blends. We showed that these formulations could have similar wear and significantly improved mechanical properties compared to currently available highly cross-linked UHMWPEs. We believe that these materials can enable thinner implant forms and more anatomical designs in joint arthroplasty and may provide a feasible alternative to metal-on-metal implants. (c) 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:5966, 2012 C1 [Oral, Ebru; Neils, Andrew L.; Lyons, Chelsea; Fung, Mitchell; Doshi, Brinda; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. [Oral, Ebru; Muratoglu, Orhun K.] Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA USA. [Lyons, Chelsea] MIT, Dept Mat Sci & Engn, Boston, MA USA. RP Oral, E (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. EM eoral@partners.org NR 27 TC 8 Z9 8 U1 3 U2 31 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD JAN PY 2013 VL 31 IS 1 BP 59 EP 66 DI 10.1002/jor.22195 PG 8 WC Orthopedics SC Orthopedics GA 043SO UT WOS:000311568700009 PM 22847503 ER PT J AU Xu, HZ Yu, YM Ma, H Carter, EA Fagan, S Tompkins, RG Fischman, AJ AF Xu, Hongzhi Yu, Yong-Ming Ma, Harry Carter, Edward A. Fagan, Shawn Tompkins, Ronald G. Fischman, Alan J. TI Glucose metabolism during the early "flow phase" after burn injury SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE PET; Euglycemic insulin clamp; Insulin resistance; Stable isotopic tracer study ID POSITRON-EMISSION-TOMOGRAPHY; DEPENDENT DIABETES-MELLITUS; MUSCLE PROTEIN-SYNTHESIS; SKELETAL-MUSCLE; BLOOD-FLOW; INSULIN-RESISTANCE; HYPERGLYCEMIA; LIVER; HETEROGENEITY; STIMULATION AB Background: Burn injury (BI) is associated with insulin resistance (IR) and hyperglycemia which complicate clinical management. We investigated the impact of BI on glucose metabolism in a rabbit model of BI using a combination of positron emission tomography (PET) and stable isotope studies under euglycemic insulin clamp (EIC) conditions. Materials and methods: Twelve male rabbits were subjected to either full-thickness BI (B) or sham burn. An EIC condition was established by constant infusion of insulin, concomitantly with a variable rate of dextrose infusion 3 d after treatment. PET imaging of the hind limbs was conducted to determine the rates of peripheral O-2 and glucose utilization. Each animal also received a primed constant infusion of [6,6-H-2(2)] glucose to determine endogenous glucose production. Results: The fasting blood glucose in the burned rabbits was higher than that in the sham group. Under EIC conditions, the sham burn group required more exogenous dextrose than the B group to maintain blood glucose at physiological levels (22.2 +/- 2.6 versus 13.3 +/- 2.9 mg/min, P < 0.05), indicating a state of IR. PET imaging demonstrated that the rates of O-2 consumption and F-18 2-fluoro-2-deoxy-D-glucose utilization by skeletal muscle remained at similar levels in both groups. Hepatic gluconeogenesis determined by the stable isotope tracer study was found significantly increased in the B group. Conclusions: These findings demonstrated that hyperglycemia and IR develop during the early "flow phase" after BI. Unsuppressed hepatic gluconeogenesis, but not peripheral skeletal muscular utilization of glucose, contributes to hyperglycemia at this stage. Published by Elsevier Inc. C1 [Xu, Hongzhi] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Xu, Hongzhi] Shriners Hosp Children, Boston, MA USA. RP Xu, HZ (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM hongzhi2008@gmail.com FU NIDDK NIH HHS [P30 DK040561]; NIGMS NIH HHS [P50 GM021700] NR 41 TC 3 Z9 4 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JAN PY 2013 VL 179 IS 1 BP E83 EP E90 DI 10.1016/j.jss.2012.02.037 PG 8 WC Surgery SC Surgery GA 051LW UT WOS:000312129700011 PM 22459295 ER PT J AU Saylor, PJ Smith, MR AF Saylor, Philip J. Smith, Matthew R. TI Metabolic Complications of Androgen Deprivation Therapy for Prostate Cancer SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; gonadotropin-releasing hormone agonists; cardiovascular diseases; diabetes mellitus; obesity ID CORONARY-HEART-DISEASE; HORMONE AGONIST TREATMENT; BONE-MINERAL DENSITY; LEAN BODY-MASS; CARDIOVASCULAR MORTALITY; SUPPRESSION THERAPY; INSULIN SENSITIVITY; ARTERIAL STIFFNESS; BLOOD CHOLESTEROL; RISK FACTOR AB Purpose: Androgen deprivation therapy has a variety of well recognized adverse effects including vasomotor flushing, loss of libido, fatigue, gynecomastia, anemia and osteoporosis. This review focuses on the more recently described metabolic complications of androgen deprivation therapy including obesity, insulin resistance and lipid alterations as well as the association of androgen deprivation therapy with diabetes and cardiovascular disease. Materials and Methods: We reviewed the medical literature using the PubMed (R) search terms prostate cancer, androgen deprivation therapy, gonadotropin-releasing hormone agonists, obesity, insulin resistance, lipids, diabetes, cardiovascular disease and myocardial infarction. We provide a focused review and our perspective on the relevant literature. Results: Androgen deprivation therapy decreases lean mass and increases fat mass. It also decreases insulin sensitivity while increasing low density lipoprotein cholesterol, high density lipoprotein cholesterol and triglycerides. Consistent with these adverse metabolic effects, androgen deprivation therapy may be associated with a greater incidence of diabetes and cardiovascular disease. Some of these androgen deprivation therapy related metabolic changes (obesity, insulin resistance and increased triglycerides) overlap with features of the metabolic syndrome. However, in contrast to the metabolic syndrome, androgen deprivation therapy increases subcutaneous fat and high density lipoprotein cholesterol. Conclusions: Androgen deprivation therapy increases obesity, decreases insulin sensitivity and adversely alters lipid profiles. It may be associated with a greater incidence of diabetes and cardiovascular disease. The benefits of androgen deprivation therapy should be weighed against these and other potential harms. Little is known about the optimal strategy to mitigate the adverse metabolic effects of androgen deprivation therapy. Thus, we recommend an emphasis on existing strategies for screening and treatment that have been documented to reduce the risk of diabetes and cardiovascular disease in the general population. C1 [Saylor, Philip J.; Smith, Matthew R.] Massachusetts Gen Hosp, Dept Oncol, Ctr Canc, Boston, MA 02114 USA. RP Saylor, PJ (reprint author), Massachusetts Gen Hosp, Dept Med Oncol, Ctr Canc, 55 Fruit St,POB 2-221, Boston, MA 02114 USA. EM psaylor@partners.org FU National Institutes of Health [5K24CA121990-02]; Prostate Cancer Foundation; Lance Armstrong Foundation FX Supported by a National Institutes of Health K24 Midcareer Investigator Award (5K24CA121990-02), and grants from the Prostate Cancer Foundation and Lance Armstrong Foundation. NR 57 TC 49 Z9 50 U1 3 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JAN PY 2013 VL 189 IS 1 SU S BP S34 EP S42 DI 10.1016/j.juro.2012.11.017 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 051BT UT WOS:000312100000009 PM 23234628 ER PT J AU Smith, MR Morton, RA Barnette, KG Sieber, PR Malkowicz, SB Rodriguez, D Hancock, ML Steiner, MS AF Smith, Matthew R. Morton, Ronald A. Barnette, K. Gary Sieber, Paul R. Malkowicz, S. Bruce Rodriguez, Domingo Hancock, Michael L. Steiner, Mitchell S. TI Toremifene to Reduce Fracture Risk in Men Receiving Androgen Deprivation Therapy for Prostate Cancer SO JOURNAL OF UROLOGY LA English DT Article DE osteoporosis; prostatic neoplasms; selective estrogen receptor modulators; toremifene ID RANDOMIZED CONTROLLED-TRIAL; BONE LOSS; VERTEBRAL FRACTURES; HORMONE AGONISTS; OSTEOPOROSIS; RALOXIFENE; ESTROGEN; DISEASE AB Purpose: Androgen deprivation therapy is associated with fracture risk in men with prostate cancer. We assessed the effects of toremifene, a selective estrogen receptor modulator, on fracture incidence in men receiving androgen deprivation therapy during a 2-year period. Materials and Methods: In this double-blind, placebo controlled phase III study 646 men receiving androgen deprivation therapy for prostate cancer were assigned to toremifene (80 mg by mouth daily) and 638 were assigned to placebo. Subjects were followed for 2 years. The primary study end point was new vertebral fractures. Secondary end points included fragility fractures, bone mineral density and lipid changes. Results: The 2-year incidence of new vertebral fractures was 4.9% in the placebo group vs 2.5% in the toremifene group, a significant relative risk reduction of 50% (95% CI -1.5 to 75.0, p = 0.05). Toremifene significantly increased bone mineral density at the lumbar spine, hip and femoral neck vs placebo (p <0.0001 for all comparisons). There was a concomitant decrease in markers of bone turnover (p <0.05 for all comparisons). Toremifene also significantly improved lipid profiles. Venous thromboembolic events occurred more frequently with toremifene than placebo with 7 subjects (1.1%) in the placebo group experiencing a venous thromboembolic event vs 17 (2.6%) in the toremifene group. Other adverse events were similar between the groups. Conclusions: Toremifene significantly decreased the incidence of new vertebral fractures in men receiving androgen deprivation therapy for prostate cancer. It also significantly improved bone mineral density, bone turnover markers and serum lipid profiles. C1 [Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Morton, Ronald A.; Barnette, K. Gary; Rodriguez, Domingo; Hancock, Michael L.; Steiner, Mitchell S.] GTx Inc, Memphis, TN USA. [Sieber, Paul R.] Urol Associates Lancaster, Lancaster, PA USA. [Malkowicz, S. Bruce] Univ Penn, Dept Surg, Div Urol, Philadelphia, PA 19104 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Yawkey 7038,55 Fruit St, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu FU GTx Inc.; National Institutes of Health [5K24CA121990-02]; Prostate Cancer Foundation; GTx; Amgen; Astellas; Endo Pharma; Tengion FX Supported by GTx Inc.; Recipient of a National Institutes of Health K24 Midcareer Investigator Award (5K24CA121990-02) and awards from the Prostate Cancer Foundation.; Financial interest and/or other relationship with GTx and Amgen.; Financial interest and/or other relationship with Astellas, Endo Pharma, Tengion and GTx. NR 28 TC 14 Z9 14 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JAN PY 2013 VL 189 IS 1 SU S BP S45 EP S50 DI 10.1016/j.juro.2012.11.016 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 051BT UT WOS:000312100000012 PM 23234631 ER PT J AU Torres, AJ Contento, RL Gordo, S Wucherpfennig, KW Love, JC AF Torres, Alexis J. Contento, Rita Lucia Gordo, Susana Wucherpfennig, Kai W. Love, J. Christopher TI Functional single-cell analysis of T-cell activation by supported lipid bilayer-tethered ligands on arrays of nanowells SO LAB ON A CHIP LA English DT Article ID IMMUNOLOGICAL SYNAPSES; RECEPTOR MICROCLUSTERS; IN-VITRO; CLUSTERS; RESPONSES; PEPTIDE; POLY(DIMETHYLSILOXANE); REQUIREMENTS; CYTOSKELETON; RECOGNITION AB Supported lipid bilayers are an important biomolecular tool for characterizing immunological synapses. Immobilized bilayers presenting tethered ligands on planar substrates have yielded both spatio-temporal and structural insights into how T cell receptors (TCRs) reorganize during the initial formation of synapses upon recognition of peptide antigens bound to major histocompatibility complex (MHC) molecules. The prototypical configuration of these assays, however, limits the extent to which the kinetics and structure of the supramolecular activation clusters of the synapse (that occur in seconds or minutes) can be related to subsequent complex cellular responses, such as cytokine secretion and proliferation, occurring over hours to days. Here we describe a new method that allows correlative measures of both attributes with single-cell resolution by using immobilized lipid bilayers and tethered ligands on the surface of dense arrays of subnanoliter wells. This modification allows each nanowell to function as an artificial antigen-presenting cell (APC), and the synapses formed upon contact can be imaged by fluorescence microscopy. We show that the lipid bilayers remain stable and mobile on the surface of the PDMS, and that modifying the ligands tethered to the bilayer alters the structure of the resulting synapses in expected ways. Finally, we demonstrate that this approach allows the subsequent characterization of secreted cytokines from the activated human T cell clones by microengraving in both antigen-and pan-specific manners. This new technique should allow detailed investigations on how biophysical and structural aspects of the synapse influence the activation of individual T cells and their complex functional responses. C1 [Torres, Alexis J.; Contento, Rita Lucia; Love, J. Christopher] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Love, J. Christopher] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Gordo, Susana; Wucherpfennig, Kai W.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Program Immunol, Boston, MA 02215 USA. RP Love, JC (reprint author), MIT, Dept Chem Engn, Cambridge, MA 02139 USA. EM clove@mit.edu FU NIH/NIAID [5P01AI045757]; Cancer Center Support, NCI [P30-CA14051] FX This work was supported by the NIH/NIAID (5P01AI045757), and partially by Cancer Center Support (core) Grant P30-CA14051 from the NCI. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy And Infectious Diseases or the National Institutes of Health. We thank the Koch Institute Imaging Facilities and Eliza Vasile for helpful discussions and insights. J.C.L. is a Camille Dreyfus Teacher-Scholar and Latham Family Career Development Professor. NR 42 TC 25 Z9 25 U1 2 U2 57 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 J9 LAB CHIP JI Lab Chip PY 2013 VL 13 IS 1 BP 90 EP 99 DI 10.1039/c2lc40869d PG 10 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 049HN UT WOS:000311973500010 PM 23070211 ER PT J AU Nayak, L Abrey, LE Drappatz, J Gilbert, MR Reardon, DA Wen, PY Prados, M Deangelis, LM Omuro, A AF Nayak, Lakshmi Abrey, Lauren E. Drappatz, Jan Gilbert, Mark R. Reardon, David A. Wen, Patrick Y. Prados, Michael Deangelis, Lisa M. Omuro, Antonio CA N Amer Brain Tumor Consortium TI Multicenter phase II study of rituximab and temozolomide in recurrent primary central nervous system lymphoma SO LEUKEMIA & LYMPHOMA LA English DT Article DE CNS lymphoma; rituximab; temozolomide ID PRIMARY CNS LYMPHOMA; WHOLE-BRAIN RADIOTHERAPY; SALVAGE TREATMENT; METHOTREXATE; IMMUNOCHEMOTHERAPY; CHEMOTHERAPY; THERAPY AB We initiated a prospective multicenter phase II trial using rituximab and temozolomide in immunocompetent patients with progressive or recurrent primary central nervous system lymphoma (PCNSL) based on activity observed in retrospective studies. Treatment consisted of an induction phase with rituximab (750 mg/m(2)) on days 1, 8, 15 and 22 and temozolomide (150 mg/m(2)) days 1-7 and 15-21, followed by six cycles of consolidation temozolomide (150-200 mg/m(2) X 5/28 days), followed by maintenance with methylprednisolone (1 g IV every 28 days) until progression. Sixteen patients were enrolled, and a complete response was seen in 2/14 (14%) evaluable patients. The median progression-free survival was 7 weeks and median overall survival was not reached (median follow-up: 37 months). Treatment was well tolerated, but due to slow accrual and preliminary analysis suggesting futility, the trial was closed early. Given the overall modest activity, this regimen should be reserved for patients who are not candidates for other, more aggressive salvage treatments. C1 [Nayak, Lakshmi; Abrey, Lauren E.; Deangelis, Lisa M.; Omuro, Antonio] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10065 USA. [Drappatz, Jan; Wen, Patrick Y.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. [Gilbert, Mark R.] MD Anderson Canc Inst, Dept Neurooncol, Houston, TX USA. [Reardon, David A.] Duke Univ, Med Ctr, Brain Tumor Ctr Duke, Durham, NC USA. [Prados, Michael] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA. RP Omuro, A (reprint author), Mem Sloan Kettering Canc Ctr, Dept Neurol, 1275 York Ave, New York, NY 10065 USA. EM OmuroA@mskcc.org RI Gilbert, Mark/J-7494-2016; OI Gilbert, Mark/0000-0003-2556-9722; Omuro, Antonio/0000-0003-4299-3664 FU National Cancer Institute, NIH [U01-CA062399] FX This study was funded by the National Cancer Institute, NIH grant # U01-CA062399. Temozolomide was provided by Schering-Plough/Merck. This trial is registered at the Clinical-Trials.gov registry (# NCT00248534), and was presented in part at the American Society of Clinical Oncology Annual Meeting, 2011. NR 17 TC 16 Z9 19 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD JAN PY 2013 VL 54 IS 1 BP 58 EP 61 DI 10.3109/10428194.2012.698736 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 049UP UT WOS:000312009200014 PM 22656234 ER PT J AU Mai, CL Firth, PG Yaster, M AF Mai, Christine L. Firth, Paul G. Yaster, Myron TI History of pediatric anesthesia timeline SO PEDIATRIC ANESTHESIA LA English DT Editorial Material C1 [Mai, Christine L.; Firth, Paul G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. [Mai, Christine L.; Yaster, Myron] Johns Hopkins Med Inst, Dept Anesthesiol Crit Care Med & Pediat, Baltimore, MD 21205 USA. [Mai, Christine L.; Firth, Paul G.] Harvard Univ, Sch Med, Dept Anesthesia, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Mai, CL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1155-5645 J9 PEDIATR ANESTH JI Pediatr. Anesth. PD JAN PY 2013 VL 23 IS 1 BP 1 EP 2 DI 10.1111/pan.12094 PG 2 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA 051OI UT WOS:000312136400001 PM 23216933 ER PT J AU Mai, CL Yaster, M Firth, P AF Mai, Christine L. Yaster, Myron Firth, Paul TI The development of continuous positive airway pressure: an interview with Dr. George Gregory SO PEDIATRIC ANESTHESIA LA English DT Article DE George Gregory; continuous positive airway pressure; hyaline membrane disease; idiopathic respiratory distress syndrome; neonatal respiratory distress syndrome ID HYALINE-MEMBRANE DISEASE; RESPIRATORY-DISTRESS-SYNDROME; MECHANICAL VENTILATION; PEDIATRIC ANESTHESIA; NEWBORN INFANTS; CRITICAL-CARE; HALOTHANE; FRUCTOSE-1,6-BISPHOSPHATE; REQUIREMENT; SURFACTANT AB George Gregory, M.D. (1934-), Professor Emeritus at the University of California, San Francisco, has made numerous contributions to neonatology and pediatric anesthesia through his research efforts and authoritative textbook, Gregory's Pediatric Anesthesia. However he identified his defining moment as the occasion he saved the life of an infant suffering from neonatal respiratory distress syndrome by using continuous positive airway pressure (CPAP) ventilation. The development of CPAP by Gregory revolutionized the treatment of premature infants with respiratory failure. Prior to the creation of this treatment, the mortality rate of neonates with respiratory distress syndrome was >50%. The innovation markedly improved the ventilation of infants with respiratory distress and led to significant improvements in survival rates. Based on an interview with Dr. Gregory, this article describes the discovery of CPAP and reviews his career in advancing pediatric anesthesia and critical care medicine. C1 [Mai, Christine L.; Firth, Paul] Massachusetts Gen Hosp, Dept Anesthesia Crit Care Med & Pain Med, Boston, MA 02114 USA. [Mai, Christine L.; Yaster, Myron] Johns Hopkins Med Inst, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA. [Mai, Christine L.; Firth, Paul] Massachusetts Eye & Ear Infirm, Dept Anesthesia, Boston, MA 02114 USA. RP Mai, CL (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care Med & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM cmai1@partners.org NR 31 TC 4 Z9 4 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1155-5645 J9 PEDIATR ANESTH JI Pediatr. Anesth. PD JAN PY 2013 VL 23 IS 1 BP 3 EP 8 DI 10.1111/pan.12075 PG 6 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA 051OI UT WOS:000312136400002 PM 23170829 ER PT J AU Tsao, AC Lovich, MA Parker, MJ Zheng, H Peterfreund, RA AF Tsao, Amy C. Lovich, Mark A. Parker, Michael J. Zheng, Hui Peterfreund, Robert A. TI Delivery interaction between co-infused medications: an in vitro modeling study of microinfusion SO PEDIATRIC ANESTHESIA LA English DT Article DE drug infusion; critical illness; patient safety; pediatric patients ID DRUG-DELIVERY; DEAD-VOLUME; SYRINGE PUMPS; FLOW-RATES; DYNAMICS; INFUSIONS; IMPACT; DELAYS AB Objective: To test the hypothesis that steady-state drug delivery by continuous infusion is predictably affected by a second drug infusion in the same lumen. Background: Clinicians commonly administer two drugs by continuous infusion through one central venous catheter lumen (co-infusion). To limit fluid delivery, low flow rate carriers transport concentrated drug solutions a method called microinfusion. How microinfusion delivery of one drug is affected by a second drug infusion has not been explored. Methods: Two water-soluble dyes, tartrazine and erioglaucine, infused at 3 ml center dot h-1, modeled drug delivery through a four stopcock linear manifold and catheter lumen. A pump drove a carrier fluid (10 ml center dot h-1). After tartrazine reached steady-state delivery, erioglaucine entered downstream or upstream of the tartrazine infusion. Quantitative spectrophotometry measured dye delivery. Results: Starting erioglaucines infusion upstream of tartrazines entry caused a transient tartrazine bolus (duration 10 min, peak drug delivery 20% higher than target levels). Starting erioglaucines infusion downstream produced a similar amplitude, briefer, bolus. Stopping the erioglaucine infusion caused a transient reduction in tartrazine delivery. Measured delivery profiles were comparable to prediction models. Conclusions: We confirmed the hypothesis that delivery of one infused drug is transiently affected by starting or stopping a second drug infusion in the same line. The magnitude of the changes can be estimated quantitatively. The clinical impact depends on the drugs being co-infused and patient sensitivity, but could be clinically important; the findings have safety implications for infused medication delivery to critically ill or anesthetized children. We recommend minimizing infusion system dead volumes, connecting the most essential infusion(s) to the main fluid pathway as close as possible to the patient, and recognizing the potential for unintended alterations in delivery when multiple drugs co-infuse. C1 [Tsao, Amy C.; Peterfreund, Robert A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Lovich, Mark A.] St Elizabeths Med Ctr, Dept Anesthesiol & Pain Med, Boston, MA USA. [Parker, Michael J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Pulm Crit Care & Sleep Med, Sch Med, Boston, MA 02215 USA. [Zheng, Hui] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA USA. RP Peterfreund, RA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Jackson 439,55 Fruit St, Boston, MA 02114 USA. EM rpeterfreund@partners.org NR 10 TC 10 Z9 11 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1155-5645 J9 PEDIATR ANESTH JI Pediatr. Anesth. PD JAN PY 2013 VL 23 IS 1 BP 33 EP 39 DI 10.1111/j.1460-9592.2012.03898.x PG 7 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA 051OI UT WOS:000312136400006 PM 22712626 ER PT J AU Bai, B Li, QZ Leahy, RM AF Bai, Bing Li, Quanzheng Leahy, Richard M. TI Magnetic Resonance-Guided Positron Emission Tomography Image Reconstruction SO SEMINARS IN NUCLEAR MEDICINE LA English DT Review ID TIME-OF-FLIGHT; PARTIAL-VOLUME CORRECTION; ANATOMICAL PRIORS; PET DATA; BAYESIAN RECONSTRUCTION; MAXIMUM-LIKELIHOOD; SIDE INFORMATION; PERFORMANCE EVALUATION; COMPUTED-TOMOGRAPHY; SPATIAL-RESOLUTION AB The resolution of positron emission tomography (PET) images is limited by the physics of positron-electron annihilation and instrumentation for photon coincidence detection. Model-based methods that incorporate accurate physical and statistical models have produced significant improvements in reconstructed image quality when compared with filtered backprojection reconstruction methods. However, it has often been suggested that by incorporating anatomical information, the resolution and noise properties of PET images could be further improved, leading to better quantitation or lesion detection. With the recent development of combined MR-PET scanners, we can now collect intrinsically coregistered magnetic resonance images. It is therefore possible to routinely make use of anatomical information in PET reconstruction, provided appropriate methods are available. In this article, we review research efforts over the past 20 years to develop these methods. We discuss approaches based on the use of both Markov random field priors and joint information or entropy measures. The general framework for these methods is described, and their performance and longer-term potential and limitations are discussed. Semin Nucl Med 43:30-44 (C) 2013 Elsevier Inc. All rights reserved. C1 [Leahy, Richard M.] Univ So Calif, Dept Elect Engn, Signal & Image Proc Inst, Los Angeles, CA 90089 USA. [Bai, Bing] Univ So Calif, Dept Radiol, Los Angeles, CA 90089 USA. [Li, Quanzheng] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Li, Quanzheng] Harvard Univ, Sch Med, Boston, MA USA. RP Leahy, RM (reprint author), Univ So Calif, Dept Elect Engn, Signal & Image Proc Inst, 3740 McClintock Ave,EEB 400,MC 2564, Los Angeles, CA 90089 USA. EM leahy@sipi.usc.edu FU [R01 EB010197]; [R21 CA149587]; [R01 EB013293] FX This work was supported by grants R01 EB010197, R21 CA149587, and R01 EB013293. NR 79 TC 25 Z9 25 U1 1 U2 24 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0001-2998 EI 1558-4623 J9 SEMIN NUCL MED JI Semin. Nucl. Med. PD JAN PY 2013 VL 43 IS 1 BP 30 EP 44 DI 10.1053/j.semnuclmed.2012.08.006 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 050GT UT WOS:000312041900005 PM 23178087 ER PT J AU Ouyang, JS Li, QZ El Fakhri, G AF Ouyang, Jinsong Li, Quanzheng El Fakhri, Georges TI Magnetic Resonance-Based Motion Correction for Positron Emission Tomography Imaging SO SEMINARS IN NUCLEAR MEDICINE LA English DT Review ID RESPIRATORY GATED PET; ATTENUATION CORRECTION; HEAD MOVEMENT; RECONSTRUCTION; MRI; REGISTRATION; IMAGES; RESOLUTION; TRACKING; IMPACT AB Positron emission tomography (PET) image quality is limited by patient motion. Emission data are blurred owing to cardiac and/or respiratory motion. Although spatial resolution is 4 mm for standard clinical whole-body PET scanners, the effective resolution can be as low as 1 cm owing to motion. Additionally, the deformation of attenuation medium causes image artifacts. Previously, gating has been used to "freeze" the motion, but led to significantly increased noise level. Simultaneous PET/magnetic resonance (MR) modality offers a new way to perform PET motion correction. MR can be used to measure 3-dimensional motion fields, which can then be incorporated into the iterative PET reconstruction to obtain motion-corrected PET images. In this report, we present MR imaging techniques to acquire dynamic images, a nonrigid image registration algorithm to extract motion fields from acquired MR images, and a PET reconstruction algorithm with motion correction. We also present results from both phantom and in vivo animal PET/MR studies. We demonstrate that MR-based PET motion correction using simultaneous PET/MR improves image quality and lesion detectability compared with gating and no motion correction. Semin Nucl Med 43:60-67 (C) 2013 Elsevier Inc. All rights reserved. C1 [El Fakhri, Georges] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Adv Radiol Sci,Dept Radiol, Boston, MA 02114 USA. RP El Fakhri, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Adv Radiol Sci,Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM elfakhri@pet.mgh.harvard.edu FU NIH [R21EB012326, R01CA165221] FX We would like to acknowledge Yoann Petibon, Timothy Reese, Sc Young Chun, Xuping Zhu, and Chuan Huang at Massachusetts General Hospital for their contributions to the results presented in this article. This work was supported in part by NIH R21EB012326 and R01CA165221. NR 52 TC 30 Z9 30 U1 1 U2 22 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0001-2998 J9 SEMIN NUCL MED JI Semin. Nucl. Med. PD JAN PY 2013 VL 43 IS 1 BP 60 EP 67 DI 10.1053/j.semnuclmed.2012.08.007 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 050GT UT WOS:000312041900007 PM 23178089 ER PT B AU Jovanovic, I Cazalas, E Childres, I Patil, A Koybasi, O Chen, YP AF Jovanovic, Igor Cazalas, Edward Childres, Isaac Patil, Amol Koybasi, Ozhan Chen, Yong P. BE Merelli, D TI Graphene Field Effect Transistor-Based Detectors for Detection of Ionizing Radiation SO 2013 3RD INTERNATIONAL CONFERENCE ON ADVANCEMENTS IN NUCLEAR INSTRUMENTATION, MEASUREMENT METHODS AND THEIR APPLICATIONS (ANIMMA) LA English DT Proceedings Paper CT 3rd International Conference on Advancements in Nuclear Instrumentation, Measurement Methods and their Applications (ANIMMA) CY JUN 23-27, 2013 CL Marseille, FRANCE SP IEEE, IEEE Nucl & Plasma Sci Soc DE radiation detection; graphene field effect transistor AB We present the results of our recent efforts to develop novel ionizing radiation sensors based on the nanomaterial graphene. Graphene used in the field effect transistor architecture could be employed to detect the radiation-induced charge carriers produced in undoped semiconductor absorber substrates, even without the need for charge collection. The detection principle is based on the high sensitivity of graphene to ionization-induced local electric field perturbations in the electrically biased substrate. We experimentally demonstrated promising performance of graphene field effect transistors for detection of visible light, X-rays, gamma-rays, and alpha particles. We propose improved detector architectures which could result in a significant improvement of speed necessary for pulsed mode operation. C1 [Jovanovic, Igor; Cazalas, Edward] Penn State Univ, Dept Mech & Nucl Engn, University Pk, PA 16802 USA. [Childres, Isaac] Purdue Univ, Dept Phys, W Lafayette, IN 47907 USA. [Patil, Amol] Canberra Nucl Ind, Meridien, CT 06451 USA. [Koybasi, Ozhan] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. [Chen, Yong P.] Purdue Univ, Birck Nanotechnol Ctr, Dept Phys, Dept Elect & Comp Engn, W Lafayette, IN 47907 USA. RP Jovanovic, I (reprint author), Penn State Univ, Dept Mech & Nucl Engn, University Pk, PA 16802 USA. EM ijovanovic@psu.edu; ejc149@psu.edu; ichildre@purdue.edu; amol.patil@canberra.com; okoybasi@partners.org; yongchen@purdue.edu FU Department of Homeland Security [2009-DN-077-AR1036-02]; Department of Defense [HDTRA 1-09-1-0047] FX This work has been supported by Department of Homeland Security and Department of Defense under awards 2009-DN-077-AR1036-02 and HDTRA 1-09-1-0047, respectively. NR 10 TC 0 Z9 0 U1 0 U2 4 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4799-1046-5; 978-1-4799-1047-2 PY 2013 PG 5 WC Engineering, Electrical & Electronic; Instruments & Instrumentation; Nuclear Science & Technology SC Engineering; Instruments & Instrumentation; Nuclear Science & Technology GA BB8TG UT WOS:000347423600062 ER PT S AU Barbieri, R Citi, L Valenza, G Guerrisi, M Orsolini, S Tessa, C Diciotti, S Toschi, N AF Barbieri, Riccardo Citi, Luca Valenza, Gaetano Guerrisi, Maria Orsolini, Stefano Tessa, Carlo Diciotti, Stefano Toschi, Nicola GP IEEE TI Increased Instability of Heartbeat Dynamics in Parkinson's Disease SO 2013 COMPUTING IN CARDIOLOGY CONFERENCE (CINC) SE Computing in Cardiology Conference LA English DT Proceedings Paper CT 40th Annual Meeting on Computing in Cardiology (CinC) CY SEP 22-25, 2013 CL Zaragoza, SPAIN SP EMB, IEEE, PhysioNet, Mortara, Univ Inst Investigac Ingn Aragon, Univ Zaragoza, Philips, Escuela Ingn Arquitectura, Univ Zaragoza, GE Healthcare Life Sci, Cardiolund, Ciber-BBN, Centro Investigac Biomedica Red Bioingenieria, Biomateriales Nanomedicina, lOP Publishing, Zoll, Museo Ibercaja, Goya Zaragoza, ESC Working Grp, e-Cardiol, Unive Zaragoza, GTC, Commun Technologies Grp,, Unive Zaragoza, European Soc Cardiol ID RATE-VARIABILITY; PATHOPHYSIOLOGY; DISORDERS AB Parkinson's disease (PD) has been reported to involve postganglionic sympathetic failure and, in 25% of patients, autonomic failure. In this work we investigate autonomic dynamics in PD using a novel methodology able to provide instantaneous estimates of the Lyapunov spectrum within a point process framework. Physiological signals were recorded from 10 healthy subjects and 9 cognitively preserved PD patients. We computed conventional heart rate variability (HRV) features as well as the full Lyapunov spectrum over 600s recordings at rest, and tested for significant group effects using a general linear model taking into account age and gender as nuisance covariates. Additionally, the discriminatory power of all features was tested by training a Support Vector Machine (SVM) classifier combined with recursive feature elimination (RFE) with a variable number of target features. The first and second Lyapunov exponents were significantly higher (p<0.05) in PD patients vs. controls. No other HRV measure differed significantly between groups. The best classification performance (75% sensitivity, 80% specificity, area under ROC curve 0.8) was attained when instructing RFE to retain 2 features, where the algorithm selected the first and second Lyapunov exponents. Our results suggest that autonomic control in PD entails a preponderance of nonlinear, more unstable heartbeat dynamics with respect to controls. This could point to possible autonomic dysfunction which cannot be detected by conventional HRV measures. C1 [Barbieri, Riccardo; Citi, Luca; Valenza, Gaetano; Toschi, Nicola] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Citi, Luca] Univ Essex, Colchester CO4 3SQ, Essex, England. [Valenza, Gaetano] Univ Pisa, Pisa, Italy. [Orsolini, Stefano; Diciotti, Stefano] Univ Florence, Florence, Italy. [Tessa, Carlo] Versilia Hosp, Viareggio, Italy. [Guerrisi, Maria; Toschi, Nicola] Univ Roma Tor Vergata, Rome, Italy. RP Barbieri, R (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,Jackson 4, Boston, MA 02114 USA. EM barbieri@neurostat.mit.edu RI Toschi, Nicola/J-2555-2012; OI Toschi, Nicola/0000-0003-1929-5833; GUERRISI, MARIA GIOVANNA/0000-0002-7456-4349; Diciotti, Stefano/0000-0001-8778-7819; Barbieri, Riccardo/0000-0001-9381-3833; Valenza, Gaetano/0000-0001-6574-1879 NR 16 TC 2 Z9 2 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2325-887X BN 978-1-4799-0884-4 J9 COMPUT CARDIOL CONF PY 2013 VL 40 BP 89 EP 92 PG 4 WC Computer Science, Interdisciplinary Applications; Engineering, Multidisciplinary; Engineering, Biomedical SC Computer Science; Engineering GA BC1AL UT WOS:000349898700024 ER PT S AU Meo, M Zarzoso, V Meste, O Latcu, DG Saoudi, N Barbieri, R AF Meo, Marianna Zarzoso, Vicente Meste, Olivier Latcu, Decebal G. Saoudi, Nadir Barbieri, Riccardo GP IEEE TI Point Process Modeling of R-R Interval Dynamics during Atrial Fibrillation SO 2013 COMPUTING IN CARDIOLOGY CONFERENCE (CINC) SE Computing in Cardiology Conference LA English DT Proceedings Paper CT 40th Annual Meeting on Computing in Cardiology (CinC) CY SEP 22-25, 2013 CL Zaragoza, SPAIN SP EMB, IEEE, PhysioNet, Mortara, Univ Inst Investigac Ingn Aragon, Univ Zaragoza, Philips, Escuela Ingn Arquitectura, Univ Zaragoza, GE Healthcare Life Sci, Cardiolund, Ciber-BBN, Centro Investigac Biomedica Red Bioingenieria, Biomateriales Nanomedicina, lOP Publishing, Zoll, Museo Ibercaja, Goya Zaragoza, ESC Working Grp, e-Cardiol, Unive Zaragoza, GTC, Commun Technologies Grp,, Unive Zaragoza, European Soc Cardiol AB Atrial fibrillation (AF) is the most common arrhythmia, and one of the main causes of ictus and strokes. Effective treatments for AF are still unknown, as its effects on the heart substrate have not been clearly quantified yet. One of the main lines of investigation aims at characterizing ventricular response by looking at its effects on heartbeat interval dynamics. Most of the standard approaches have focused on RR interval (RRI) histogram parameters albeit with several shortcomings, such as bin width dependence or lack of attention to the time-varying dynamical structure. In this study, we model heartbeat interval series as a history-dependent inverse Gaussian (HDIG) point process where the history for each RRI prediction is a linear regression of the previous RRIs. As opposed to classical non-parametric methods, the heart rate (HR) variability features derived from the proposed parametric model provide a physiologically more consistent characterization during AF, and can clearly discriminate AF from sinus rhythm (SR) subjects. Analysis of 36 patients affected by persistent AF and 18 controls shows that RRI distributions are more right-skewed and affected by higher variability during AF (skewness of 0.63 +/- 0.29 in AF and of 0.17 +/- 0.16 in SR, p=7.6 +/- 10(-8;) HR standard deviation of 18.73 +/- 10.64 bpm in AF and 4.66 +/- 4.75 bpm in SR, p=2.3 +/- 10(-6)). Our results demonstrate that we can extract valuable information associated with AF from RRI series by using a point process framework. C1 [Meo, Marianna; Zarzoso, Vicente; Meste, Olivier] Univ Nice Sophia Antipolis, Lab Informat Signaux & Syst Sophia Antipolis I3S, Nice, France. [Saoudi, Nadir] Ctr Hosp Princesse Grace, Serv Cardiol, Monaco, Monaco. [Latcu, Decebal G.; Barbieri, Riccardo] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, Boston, MA 02114 USA. RP Meo, M (reprint author), UNS, Lab I3S, CNRS, 2000,Route Lucioles Algorithmes Bat Euclide B, F-06903 Sophia Antipolis, France. EM meo@i3s.unice.fr OI Barbieri, Riccardo/0000-0001-9381-3833 NR 7 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2325-887X BN 978-1-4799-0884-4 J9 COMPUT CARDIOL CONF PY 2013 VL 40 BP 1043 EP 1046 PG 4 WC Computer Science, Interdisciplinary Applications; Engineering, Multidisciplinary; Engineering, Biomedical SC Computer Science; Engineering GA BC1AL UT WOS:000349898700263 ER PT S AU Chang, EW Cheng, JT Roosli, C Rosowski, JJ Yun, SH AF Chang, E. W. Cheng, J. T. Roosli, C. Rosowski, J. J. Yun, S. H. GP IEEE TI Functional optical coherence tomography for imaging middle ear dynamics SO 2013 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO) SE Conference on Lasers and Electro-Optics LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO) CY JUN 09-14, 2013 CL San Jose, CA AB No currently available clinical technique is capable of visualizing and quantifying the structure and function of the middle ear. Various pathologies directly impede the conduction of sound-induced vibrations through the human middle ear, and thereby produce a 'conductive' hearing loss. Direct clinical assessment of sound conduction by middle ear structures has been limited to measurements of the average sound-induced vibration of the eardrum or the motion of single locations on the drum. In contrast, the optical coherence tomography (OCT) technology we introduce allows direct observation of the structure and sound-induced motions of a large fraction of the eardrum surface as well the ossicles within the ear. We use OCT to take three-dimensional volumetric snapshots of the moving eardrum and the ossicular chain behind the eardrum in a cadaveric chinchilla with which can generate 3D amplitude and phase maps. Our functional OCT technique can accurately image middle ear structures with a resolution of 10-20 microns and measure ossicular movements with sub-nanometer scale resolution with a temporal resolution of 50 microseconds. C1 [Chang, E. W.; Yun, S. H.] Wellman Ctr Photomed, Boston, MA 02114 USA. [Cheng, J. T.; Roosli, C.; Rosowski, J. J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Chang, EW (reprint author), Wellman Ctr Photomed, Boston, MA 02114 USA. EM echang@psicorp.com NR 4 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2160-9020 BN 978-1-55752-973-2 J9 CONF LASER ELECTR PY 2013 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BC7WX UT WOS:000355262501092 ER PT S AU Hu, DJJ Yan, L Steinvurzel, P Gora, M Lu, W Ramachandran, S Wang, Y Tearney, GJ AF Hu, D. J. J. Yan, L. Steinvurzel, P. Gora, M. Lu, W. Ramachandran, S. Wang, Y. Tearney, G. J. GP IEEE TI Extended focus optical coherence tomography with optical fiber based Bessel beam illumination SO 2013 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO) SE Conference on Lasers and Electro-Optics LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO) CY JUN 09-14, 2013 CL San Jose, CA ID DEPTH AB We demonstrate an extended depth of focus (DOF) for optical coherence tomography (OCT) using a Bessel-like higher order fiber mode. The DOF is enhanced by 7x and the lateral resolution is about 10 mu m. C1 [Hu, D. J. J.; Gora, M.; Lu, W.; Tearney, G. J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hu, D. J. J.; Wang, Y.] Inst Infocomm Res, RF & Opt Dept, Singapore, Singapore. [Yan, L.; Steinvurzel, P.; Ramachandran, S.] Boston Univ, Deptment Elect & Comp Engn, Boston, MA 02215 USA. RP Hu, DJJ (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM gtearney@partners.org RI Yan, Lu/B-8766-2008; HU, Dora Juan Juan/J-2995-2016 OI HU, Dora Juan Juan/0000-0001-8822-3900 NR 9 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2160-9020 BN 978-1-55752-973-2 J9 CONF LASER ELECTR PY 2013 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BC7WX UT WOS:000355262501097 ER PT S AU Vakoc, B AF Vakoc, Benjamin GP IEEE TI OCT Sources: Current Limitations and Future Development Needs SO 2013 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO) SE Conference on Lasers and Electro-Optics LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO) CY JUN 09-14, 2013 CL San Jose, CA AB Swept-wavelength laser sources are an essential and enabling technology in the growing clinical adoption of optical coherence tomography (OCT). In this talk, we will review the advantages and limitations of available OCT source technologies. C1 [Vakoc, Benjamin] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Vakoc, Benjamin] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Vakoc, B (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM vakoc.benjamin@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2160-9020 BN 978-1-55752-973-2 J9 CONF LASER ELECTR PY 2013 PG 1 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BC7WX UT WOS:000355262503228 ER PT S AU Yan, L Auksorius, E Bozinovic, N Tearney, GJ Ramachandran, S AF Yan, L. Auksorius, E. Bozinovic, N. Tearney, G. J. Ramachandran, S. GP IEEE TI Optical Fiber Vortices for STED Nanoscopy SO 2013 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO) SE Conference on Lasers and Electro-Optics LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO) CY JUN 09-14, 2013 CL San Jose, CA ID MICROSCOPY AB We demonstrate the first proof of concept of a fiber-based STED nanoscopy illumination system. The fiber yields naturally co-aligned vortex (dark-spot size similar to 198nm) and Gaussian beams (size similar to 340nm), potentially enabling sub-30nm resolution imaging. C1 [Yan, L.; Bozinovic, N.; Ramachandran, S.] Boston Univ, Dept Elect & Comp Engn, Boston, MA 02215 USA. [Auksorius, E.; Tearney, G. J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Yan, L (reprint author), Boston Univ, Dept Elect & Comp Engn, Boston, MA 02215 USA. EM luyan@bu.edu; sidr@bu.edu RI Yan, Lu/B-8766-2008 NR 7 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2160-9020 BN 978-1-55752-973-2 J9 CONF LASER ELECTR PY 2013 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BC7WX UT WOS:000355262503099 ER PT S AU Prashanth, R Roy, SD Mandal, PK Ghosh, S AF Prashanth, R. Roy, Sumantra Dutta Mandal, Pravat K. Ghosh, Shantanu BE Harit, G Das, S TI Surface fitting in SPECT imaging useful for Detecting Parkinson's Disease and Scans Without Evidence of Dopaminergic Deficit SO 2013 FOURTH NATIONAL CONFERENCE ON COMPUTER VISION, PATTERN RECOGNITION, IMAGE PROCESSING AND GRAPHICS (NCVPRIPG) SE National Conference on Computer Vision Pattern Recognition Image Processing and Graphics LA English DT Proceedings Paper CT 4th National Conference on Computer Vision, Pattern Recognition, Image Processing and Graphics (NCVPRIPG) CY DEC 18-21, 2013 CL Jodhpur, INDIA SP Indian Inst Technol Jodhpur, Indian Unit Pattern Recognit & Artificial Intelligence DE Parkinson's disease; Early diagnosis; SPECT imaging; Image Segmentation; Surface fitting; Polynomial models ID IMPLICIT POLYNOMIALS; OBJECTS; SWEDDS; TREMOR AB Dopaminergic imaging using Single Photon Emission Computed Tomography (SPECT) with I-123-Ioflupane have shown to increase the diagnostic accuracy in Parkinson's Disease (PD). Studies show that around 10% of subjects who are clinically diagnosed as PD, have SPECT scans in the normal range and are called Scans Without Evidence of Dopaminergic Deficit (SWEDD) subjects. Subsequent follow-up on these subjects has indicated that they are unlikely to have PD. Detection and differentiation of PD and SWEDD is problematic in the early stages of the disease. Early and accurate diagnosis of PD and also SWEDD is crucial for early management, avoidance of unnecessary medical examinations and therapies; and their side-effects. We in our paper, use the SPECT images from 35 Normal, 36 PD and 38 SWEDD subjects as obtained from the Parkinson's Progression Markers Initiative (PPMI) database, to carry out intensity-based surface fitting using polynomial model. This is the first time that such kind of modeling is carried out on the SPECT images for the characterization of PD. Our results show that the surface profile in terms of model coefficients and goodness-of-fit parameters is different for Normal, Early PD and SWEDD subjects. Such kind of modeling may aid in the diagnosis of early PD and SWEDD from SPECT images. C1 [Prashanth, R.; Roy, Sumantra Dutta] Indian Inst Technol Delhi, Dept Elect Engn, New Delhi 110016, India. [Mandal, Pravat K.] Natl Brain Res Ctr, Neurospectroscopy & Neuroimaging Lab, Gurgaon 122050, Haryana, India. [Ghosh, Shantanu] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Ghosh, Shantanu] Harvard Univ, Sch Med, Boston, MA USA. RP Prashanth, R (reprint author), Indian Inst Technol Delhi, Dept Elect Engn, New Delhi 110016, India. EM eez108051@ee.iitd.ac.in; sumantra@ee.iitd.ac.in; pravat@nbrc.ac.in; shantanu@nmrmgh.harvard.edu NR 13 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2372-658X BN 978-1-4799-1588-0 J9 NAT CONF COMPUT VIS PY 2013 PG 4 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology SC Computer Science; Engineering; Imaging Science & Photographic Technology GA BC4GJ UT WOS:000352485900059 ER PT S AU Chung, CS Wang, HW Cooper, RA AF Chung, Cheng-Shiu Wang, Hongwu Cooper, Rory A. GP IEEE TI Autonomous Function of Wheelchair-Mounted Robotic Manipulators to Perform Daily Activities SO 2013 IEEE 13TH INTERNATIONAL CONFERENCE ON REHABILITATION ROBOTICS (ICORR) SE International Conference on Rehabilitation Robotics ICORR LA English DT Proceedings Paper CT 13th IEEE International Conference on Rehabilitation Robotics (ICORR) CY JUN 24-26, 2013 CL Univ Washington Campus, Seattle, WA SP IEEE, EMB, IEEE Robot & Automat Soc, Ctr Sensorimotor Neural Engn NSF Engn Res Ctr HO Univ Washington Campus DE object recognition; wheelchair; robotics; manipulation; path planning ID FRAMEWORK AB Autonomous functions for wheelchair-mounted robotic manipulators (WMRMs) allow a user to focus more on the outcome from the task - for example, eating or drinking, instead of moving robot joints through user interfaces. In this paper, we introduce a novel personal assistive robotic system based on a position-based visual servoing (PBVS) approach. The system was evaluated with a complete drinking task, which included recognizing the location of the drink, picking up the drink from a start location, conveying the drink to the proximity of the user's mouth without spilling, and placing the drink back on the table. For a drink located in front of the wheelchair, the success rate was nearly 100%. Overall, the total time of completing drinking task is within 40 seconds. C1 [Chung, Cheng-Shiu; Wang, Hongwu; Cooper, Rory A.] Dept Vet Affairs, Human Engn Res Labs, Pittsburgh, PA USA. [Chung, Cheng-Shiu; Wang, Hongwu; Cooper, Rory A.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. RP Chung, CS (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. EM Joshua.Chung.CS@gmail.com; How11@pitt.edu; rcooper@pitt.edu FU National Science Foundation; US Department of Veterans Affairs and the National Institute for Disability and Rehabilitation Research FX Research supported by the National Science Foundation, the US Department of Veterans Affairs and the National Institute for Disability and Rehabilitation Research. NR 11 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7898 BN 978-1-4673-6024-1; 978-1-4673-6022-7 J9 INT C REHAB ROBOT PY 2013 PG 6 WC Engineering, Biomedical; Robotics; Rehabilitation SC Engineering; Robotics; Rehabilitation GA BG7WC UT WOS:000391821200034 ER PT S AU Jeannis, H Grindle, GG Kelleher, A Wang, HW Brewer, B Cooper, R AF Jeannis, Hervens Grindle, Garrett G. Kelleher, Annmarie Wang, Hongwu Brewer, Bambi Cooper, Rory GP IEEE TI Initial Development of Direct Interaction for a Transfer Robotic Arm System for Caregivers SO 2013 IEEE 13TH INTERNATIONAL CONFERENCE ON REHABILITATION ROBOTICS (ICORR) SE International Conference on Rehabilitation Robotics ICORR LA English DT Proceedings Paper CT 13th IEEE International Conference on Rehabilitation Robotics (ICORR) CY JUN 24-26, 2013 CL Univ Washington Campus, Seattle, WA SP IEEE, EMB, IEEE Robot & Automat Soc, Ctr Sensorimotor Neural Engn NSF Engn Res Ctr HO Univ Washington Campus DE Direct Interaction; Strong Arm; Assistive Systems; Transfers AB The most common injuries in healthcare are related to transfers. The Strong Arm system assists caregivers in providing fully dependent transfers from an electric power wheelchair to a bed, shower bench, toilet or other surface. However, this system currently controlled by buttons could be more successful with a more intuitive method during use. This paper presents the initial development of direct interaction for a robotic transfer system called Strong Arm. Direct interaction was used to make a transfer system more intuitive to operate using a three-axis load cell. To move Strong Arm, the user must apply intentional force on any of the given axes by surpassing the axis threshold. Unintentional movement could lead to injury. The results indicate that the thresholds for each axis were at least 3.5N in X, 16.9N in Y and 5.3N in Z in order to prevent unintentional forces from a human hand that would cause the robot to move. C1 [Jeannis, Hervens; Grindle, Garrett G.; Kelleher, Annmarie; Wang, Hongwu; Cooper, Rory] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15240 USA. [Jeannis, Hervens; Grindle, Garrett G.; Kelleher, Annmarie; Wang, Hongwu; Brewer, Bambi; Cooper, Rory] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. RP Jeannis, H (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15240 USA. EM hej7@pitt.edu FU Quality of Life Engineering Research Center; NSF [EEC-0540865]; VA WARE Center of Excellence [B6789C] FX This study was funded by the Quality of Life Engineering Research Center, NSF EEC-0540865 and VA WARE Center of Excellence Grant, #B6789C. The contents of this paper do not represent the views of the Department of Veterans Affairs or the United States Government. NR 14 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7898 BN 978-1-4673-6024-1; 978-1-4673-6022-7 J9 INT C REHAB ROBOT PY 2013 PG 5 WC Engineering, Biomedical; Robotics; Rehabilitation SC Engineering; Robotics; Rehabilitation GA BG7WC UT WOS:000391821200046 ER PT S AU Fialho, AS Kaymak, U Cismondi, F Vieira, SM Reti, SR Sousa, JMC Finkelstein, SN AF Fialho, A. S. Kaymak, U. Cismondi, F. Vieira, S. M. Reti, S. R. Sousa, J. M. C. Finkelstein, S. N. GP IEEE TI Predicting Intensive Care Unit Readmissions Using Probabilistic Fuzzy Systems SO 2013 IEEE INTERNATIONAL CONFERENCE ON FUZZY SYSTEMS (FUZZ - IEEE 2013) SE IEEE International Conference on Fuzzy Systems LA English DT Proceedings Paper CT IEEE International Conference on Fuzzy Systems (FUZZ) CY JUL 07-10, 2013 CL Hyderabad, INDIA SP IEEE, IEEE Computat Intelligence Soc, IEEE Computat Intelligence Soc, Hyderabad Chapter, IEEE Computat Intelligence Soc, Calcutta Chapter DE probabilistic fuzzy systems; readmissions; intensive care unit; AUC ID DISCHARGE DECISION-MAKING; CRITICALLY-ILL PATIENTS; LOGISTIC-REGRESSION; NEURAL-NETWORKS; OUTCOMES; ICU; HOSPITALIZATION; PERFORMANCE; DEATH; RISK AB We propose the application of probabilistic fuzzy systems (PFS) to model the prediction of early readmission in intensive care unit patients and compare it with the gold-standard method - logistic regression based on the APACHE II score. PFS are characterized by the combination of the linguistic description of the system with the statistical properties of data. On one hand, results point that PFS models perform comparably to the gold-standard method, with AUC values of 0.66 +/- 0.03. On the other hand, results also show that PFS models use a significant lower number of variables which, from the clinical practice point of view, suggests improved gains in terms of simplicity. C1 [Fialho, A. S.; Cismondi, F.; Vieira, S. M.; Sousa, J. M. C.] Univ Tecn Lisboa, Inst Super Tecn, IDMEC, Av Rovisco Pais, P-1049001 Lisbon, Portugal. [Finkelstein, S. N.] MIT, Engn Syst Div, Cambridge, MA 02139 USA. [Kaymak, U.] Eindhoven Univ Technol, Sch Ind Engn, NL-5600 MB Eindhoven, Netherlands. [Reti, S. R.] Harvard Med Sch, Beth Isreal Deaconess Med Ctr, Dept Med, Div Clin Informat, Boston, MA USA. RP Fialho, AS (reprint author), Univ Tecn Lisboa, Inst Super Tecn, IDMEC, Av Rovisco Pais, P-1049001 Lisbon, Portugal. EM afialho@mit.edu RI Kaymak, Uzay/A-3364-2008; Vieira, Susana/D-1072-2009; OI Kaymak, Uzay/0000-0002-4500-9098; Vieira, Susana/0000-0001-7961-1004; Sousa, Joao M. C./0000-0002-8030-4746 FU Portuguese Government [PTDC/EMS-SIS/3220/2012]; Fundacao para a Ciencia e Tecnologia (FCT); European Science Foundation through COST Action [IC0702] FX The authors would like to acknowledge Hospital da Luz (Lisbon, Portugal) for the data provided, as well as the help and space provided by the Division of Clinical Informatics of the Beth Israel Deaconess Medical Center, the Massachusetts Institute of Technology and Eindhoven University of Technology. Both human and technical resources were available through them, and were critical for the development of this work. This work is supported by the Portuguese Government under the programs: project PTDC/EMS-SIS/3220/2012, Fundacao para a Ciencia e Tecnologia (FCT). This work was also supported by the European Science Foundation through COST Action IC0702. NR 39 TC 2 Z9 2 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1098-7584 BN 978-1-4799-0020-6 J9 IEEE INT CONF FUZZY PY 2013 DI 10.1109/FUZZ-IEEE.2013.6622414 PG 7 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BA4CO UT WOS:000335342800116 ER PT J AU Wu, F Stark, E Im, M Cho, IJ Tien, L Chen, FJ Yoon, ES Buzsaki, G Kaplan, D Berke, J Wise, KD Yoon, E AF Wu, Fan Stark, Eran Im, Maesoon Cho, Il-Joo Tien, Lee Chen, Fujun Yoon, Eui-Sung Buzsaki, Gyorgi Kaplan, David Berke, Josh Wise, Kensall D. Yoon, Euisik GP IEEE TI Implantable Neural Probes for Chronic Electrical Recording and Optical Stimulation SO 2013 IEEE INTERNATIONAL ELECTRON DEVICES MEETING (IEDM) LA English DT Proceedings Paper CT IEEE International Electron Devices Meeting (IEDM) CY DEC 09-11, 2013 CL Washington, DC SP IEEE ID BRAIN AB In order to advance the understanding of brain functions, it is critical to manipulate and monitor the neural circuitry in the cellular level. Supporting optogenetics, silicon probes with monolithically integrated waveguides and electrodes were designed and validated with in-vivo recording of photo-induced neural activity. For chronic applications, we developed a technology that utilizes a biodegradable silk coating to support probes with unique geometries and flexibility for reduced tissue reactions. Consistent recording has been observed for 5 weeks in rats. C1 [Wu, Fan; Im, Maesoon; Cho, Il-Joo; Wise, Kensall D.; Yoon, Euisik] Univ Michigan, Dept Elect Engn & Comp Sci, Ann Arbor, MI 48109 USA. [Stark, Eran; Buzsaki, Gyorgi] NYU, Neurosci Inst, New York, NY 10016 USA. [Im, Maesoon] Massachusetts Gen Hosp, Harvard Med Sch, Dept Neurosurg, Boston, MA 02114 USA. [Cho, Il-Joo; Yoon, Eui-Sung] Korea Inst Sci & Technol, Brain Sci Inst, Ctr BioMicrosyst, Seoul 136791, South Korea. [Tien, Lee; Kaplan, David] Tufts Univ, Dept Biomed Engn, Medford, MA USA. [Chen, Fujun; Berke, Josh] Univ Michigan, Dept Psychol, Ann Arbor, MI USA. RP Wu, F (reprint author), Univ Michigan, Dept Elect Engn & Comp Sci, Ann Arbor, MI 48109 USA. EM esyoon@umich.edu FU DARPA MTO [66001-12-C-4022]; NSF [ECCS-1102067]; NSF Fellowship awarded to Fan Wu FX This work was supported in part by the DARPA MTO Contract No. 66001-12-C-4022, and in part by the NSF grant ECCS-1102067 and the NSF Fellowship awarded to Fan Wu. NR 14 TC 0 Z9 0 U1 2 U2 5 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4799-2306-9 PY 2013 PG 4 WC Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Physics GA BB8FU UT WOS:000346509500052 ER PT J AU Lim, CL Serano, P Ackerman, JL AF Lim, Chin-Leong Serano, Peter Ackerman, Jerome L. BA BinSulaiman, H Awang, Z Salleh, MKM BF BinSulaiman, H Awang, Z Salleh, MKM TI Pre-amplifiers for a 15-Tesla magnetic resonance imager SO 2013 IEEE INTERNATIONAL RF AND MICROWAVE CONFERENCE (RFM) LA English DT Proceedings Paper CT IEEE International RF and Microwave Conference (RFM) CY DEC 09-11, 2013 CL Penang, MALAYSIA SP IEEE, IEEE AP MTT EMC Joint Chapter Malaysia, UWAVE SDN BHD, RF Station Malaysia, Comrel Technolog Sdn Bhd, ATM Solut M Sdn Bhd, Rohde & Schwarz Malaysia Sdn Bhd DE pre-amplifier; magnetic resonance imaging; MRI; 15 Tesla; ePHEMT AB High-field magnetic resonance imagers (MRI) give better signal-to-noise ratio (SNR) and image contrast. However clinical MRIs are currently limited to 3 Tesla (T) magnetic field strength. To create an uncommon 15 T scanner for research use, we evaluated several low-cost, intended for wireless communication, GaAs enhancement-mode pseudomorphic high electron mobility transistors (ePHEMT) in the critical pre-amplifier slot. This paper reports the experimental results that were obtained at both module and system levels. When evaluated in our prototype 15 T scanner front-end's preamplifier slot, the candidate devices' sub 1dB noise figures enabled image SNR similar to 110 in a water phantom (test object) with a standard pulse sequence. Crisp and artifact-free images could be obtained with these candidate devices. In conclusion, high performance pre-amplifiers for 15 T MRIs can be realized using low cost ePHEMTs originally marketed for wireless communications. C1 [Lim, Chin-Leong] Avago Technol, George Town, Malaysia. [Serano, Peter; Ackerman, Jerome L.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Dept Radiol, Boston, MA 02114 USA. RP Lim, CL (reprint author), Avago Technol, George Town, Malaysia. EM C.L.Lim@ieee.org RI Ackerman, Jerome/E-2646-2015 OI Ackerman, Jerome/0000-0001-5176-7496 FU U.S. National Institutes of Health [S10-RR023009] FX The 15T MRI project is supported by U.S. National Institutes of Health grant S10-RR023009. NR 4 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4799-2214-7 PY 2013 BP 295 EP + PG 2 WC Engineering, Electrical & Electronic SC Engineering GA BC0YP UT WOS:000349841000066 ER PT J AU Bian, JG Yang, K Sidky, EY Boone, JM Pan, XC AF Bian, Junguo Yang, Kai Sidky, Emil Y. Boone, John M. Pan, Xiaochuan GP IEEE TI Optimization-based Image Reconstruction from Low-dose Patient Breast CT Data SO 2013 IEEE NUCLEAR SCIENCE SYMPOSIUM AND MEDICAL IMAGING CONFERENCE (NSS/MIC) LA English DT Proceedings Paper CT 60th IEEE Nuclear Science Symposium (NSS) / Medical Imaging Conference (MIC) / 20th International Workshop on Room-Temperature Semiconductor X-ray and Gamma-ray Detectors CY OCT 27-NOV 02, 2013 CL Seoul, SOUTH KOREA SP IEEE, Inst Elect & Elect Engineers, Nucl & Plasma Sci Soc ID CONE-BEAM CT; COMPUTED-TOMOGRAPHY; ALGORITHM; DETECTOR; COEFFICIENTS; PROJECTIONS; NOISE AB Current dedicated breast-CT prototypes use analytic-based algorithms such as FDK for image reconstruction, which require a large number of densely sampled views. Because the total imaging dose delivered to a patient in a breast-CT scan is kept about the same as that in a typical two-view mammography exam, the use of a large number of views thus can lead to projection data of low SNR and images with high noise, which makes reconstruction improvement challenging. Recently, there exists increased interest in development and evaluation of optimization-based (i.e. iterative) image reconstruction algorithms for low-dose cone-beam CT (CBCT). In the work, we focus on investigation of optimization-based image reconstruction for low-dose breast CT by tailoring a TV-minimization-based algorithm, adaptive-steep-descent (ASD)-projection-onto-convex-set (POCS) algorithm, for image reconstruction from low-SNR patient data. We performed inverse-crime studies for verifying if the algorithm is solving the designed optimization program, and studied the effect of optimization program parameter, epsilon, on the reconstruction images. We also studied the change of image power spectra with epsilon and iteration numbers. The results indicate that optimization-based algorithms may improve image quality over analytic-based algorithm for low-dose dedicated breast CT. C1 [Bian, Junguo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Yang, Kai; Boone, John M.] Univ Calif Davis, Dept Radio, Davis, CA USA. [Sidky, Emil Y.] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [Pan, Xiaochuan] Univ Chicago, Dept Radiol & Radiat & Cellular Oacol, Chicago, IL 60637 USA. RP Bian, JG (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. FU National Institutes of Health (NIH) [R01s CA120540, EB000225,EB002138, CA158446] FX This work was supported in part by the National Institutes of Health (NIH) under Grants R01s CA120540, EB000225,EB002138, and CA158446. NR 27 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4799-0534-8 PY 2013 PG 5 WC Engineering, Electrical & Electronic; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BB8OY UT WOS:000347163501185 ER PT B AU Daniels, AB Kim, IK Vavvas, DG Miller, JW AF Daniels, Anthony B. Kim, Ivana K. Vavvas, Demetrios G. Miller, Joan W. BE Lim, JI TI Choroidal neovascularization: VEGF pathways SO AGE-RELATED MACULAR DEGENERATION, 3RD EDITION LA English DT Article; Book Chapter ID ENDOTHELIAL GROWTH-FACTOR; RETINAL-PIGMENT EPITHELIUM; VASCULAR-PERMEABILITY FACTOR; HYPOXIA-INDUCIBLE FACTOR-1; MESSENGER-RNA EXPRESSION; FACTOR-H POLYMORPHISM; MACULAR DEGENERATION; BRUCHS MEMBRANE; FACTOR GENE; IN-VIVO C1 [Daniels, Anthony B.; Vavvas, Demetrios G.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Daniels, Anthony B.; Kim, Ivana K.; Vavvas, Demetrios G.] Harvard Univ, Sch Med, Boston, MA USA. [Kim, Ivana K.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Ophthalmol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Ophthalmol, JW Miller Scholar Retina Res, Boston, MA 02114 USA. [Miller, Joan W.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ophthalmol, Boston, MA USA. [Miller, Joan W.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Daniels, AB (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. NR 115 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-84184-950-8; 978-1-84184-949-2 PY 2013 BP 45 EP 53 PG 9 WC Ophthalmology SC Ophthalmology GA BC2ZU UT WOS:000351467800006 ER PT B AU Daniels, AB Kim, IK Miller, JW Vavvas, DG AF Daniels, Anthony B. Kim, Ivana K. Miller, Joan W. Vavvas, Demetrios G. BE Lim, JI TI Non-VEGF related antiangiogenesis pathways for treatment of age-related macular degeneration SO AGE-RELATED MACULAR DEGENERATION, 3RD EDITION LA English DT Article; Book Chapter ID ENDOTHELIAL GROWTH-FACTOR; EPITHELIUM-DERIVED FACTOR; CHOROIDAL NEOVASCULAR MEMBRANES; SMOOTH-MUSCLE-CELLS; HUMAN OCULAR-TISSUES; PIGMENT-EPITHELIUM; UP-REGULATION; IN-VITRO; ALPHA(V)-INTEGRIN ANTAGONIST; MATRIX METALLOPROTEINASE-2 C1 [Daniels, Anthony B.; Vavvas, Demetrios G.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Daniels, Anthony B.; Kim, Ivana K.; Vavvas, Demetrios G.] Harvard Univ, Sch Med, Boston, MA USA. [Kim, Ivana K.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Ophthalmol, Boston, MA 02114 USA. [Miller, Joan W.] Harvard Univ, Sch Med, Ophthalmol, Boston, MA USA. [Miller, Joan W.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. [Vavvas, Demetrios G.] Massachusetts Eye & Ear Infirm, Ophthalmol, Boston, MA 02114 USA. [Vavvas, Demetrios G.] Massachusetts Eye & Ear Infirm, Retina Res, Boston, MA 02114 USA. RP Daniels, AB (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. NR 148 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-84184-950-8; 978-1-84184-949-2 PY 2013 BP 243 EP 254 PG 12 WC Ophthalmology SC Ophthalmology GA BC2ZU UT WOS:000351467800022 ER PT J AU Goodwin, JE AF Goodwin, Judith Eyres TI Be inspired. Be active. Be the solution SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Editorial Material C1 [Goodwin, Judith Eyres] Joslin Diabet Ctr, Joslin Hlth Solut, Boston, MA 02215 USA. RP Goodwin, JE (reprint author), Joslin Diabet Ctr, Joslin Hlth Solut, Boston, MA 02215 USA. FU Sanofi USA; Novo Nordisk; Silverlink; Dexcom SweetSpot Diabetes Care; SeeChange Health; Humedica; Humana; BettrLife FX Sponsors for 2013 were Sanofi USA, Novo Nordisk, and Silverlink, with additional funding provided by Dexcom SweetSpot Diabetes Care, SeeChange Health, Humedica, Humana, and BettrLife. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PY 2013 VL 19 SU S BP 3 EP 4 PG 2 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V44QU UT WOS:000209764300001 ER PT J AU Agler, AH Pedersen, BS Hennessy, C Davidson, E Juan-Guardela, B Tedrow, JR Correll, M Geraci, MW Kaminski, N Quackenbush, J Sciurba, FC Spira, A Schwartz, DA Yang, IV AF Agler, A. H. Pedersen, B. S. Hennessy, C. Davidson, E. Juan-Guardela, B. Tedrow, J. R. Correll, M. Geraci, M. W. Kaminski, N. Quackenbush, J. Sciurba, F. C. Spira, A. Schwartz, D. A. Yang, I. V. TI Chronic Obstructive Pulmonary Disease And Genome-Wide Dna Methylation Patterns In Lung Tissue SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Agler, A. H.; Pedersen, B. S.; Hennessy, C.; Davidson, E.; Schwartz, D. A.; Yang, I. V.] Univ Colorado Denver, Aurora, CO USA. [Juan-Guardela, B.; Tedrow, J. R.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Correll, M.; Quackenbush, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Correll, M.; Quackenbush, J.] Harvard Sch Publ Hlth, Boston, MA USA. [Geraci, M. W.] Univ Colorado, Aurora, CO USA. [Spira, A.] Boston Univ, Boston, MA 02215 USA. EM anne.agler@hotmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A5760 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838402518 ER PT J AU Au, DH Macaulay, D Jarvis, J Macaulay, D Birnbaum, HG AF Au, D. H. Macaulay, D. Jarvis, J. Macaulay, D. Birnbaum, H. G. TI Impact Of Integrated Telehealth And Care Management Program On Resource Utilization In Medicare Beneficiaries With Chronic Obstructive Pulmonary Disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Au, D. H.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Macaulay, D.] Anal Grp Inc, New York, NY USA. [Jarvis, J.; Macaulay, D.; Birnbaum, H. G.] Anal Grp Inc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A4396 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838401039 ER PT J AU Beitler, JR Malhotra, A Thompson, BT Hayden, D Bajwa, E AF Beitler, J. R. Malhotra, A. Thompson, B. T. Hayden, D. Bajwa, E. CA NHLBI Ards Network TI Hypercapnia Without Acidemia, Compared To Hypercapnia With Acidemia, Is Associated With Reduced Mortality In Ards: Results From The Nhlbi Ards Network Fluid And Catheter Treatment (fact) Trial SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Beitler, J. R.; Malhotra, A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Thompson, B. T.; Hayden, D.; Bajwa, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jbeitler@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A6088 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838403078 ER PT J AU Beloiartsev, A Baron, DM Ventocilla, C Winkler, JD Morisseau, C Hammock, BD Bloch, KD Zapol, WM AF Beloiartsev, A. Baron, D. M. Ventocilla, C. Winkler, J. D. Morisseau, C. Hammock, B. D. Bloch, K. D. Zapol, W. M. TI Effects Of Epoxide Hydrolase Inhibition On Pulmonary Hemodynamics And Gas Exchange In Ovine Aspiration Lung Injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Beloiartsev, A.; Baron, D. M.; Bloch, K. D.; Zapol, W. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ventocilla, C.; Winkler, J. D.] Univ Penn, Philadelphia, PA 19104 USA. [Morisseau, C.; Hammock, B. D.] Univ Calif Davis, Davis, CA 95616 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A2110 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839101282 ER PT J AU Calverley, PM Similowski, T Eriksson, GS Jenkins, CR Anzueto, A Make, BJ Fageras, M Persson, A Postma, D AF Calverley, P. M. Similowski, T. Eriksson, G. S. Jenkins, C. R. Anzueto, A. Make, B. J. Fageras, M. Persson, A. Postma, D. TI Time Dependency Of Exacerbations And Study Drop-Out Among Patients With Moderate, Severe, And Very Severe COPD SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Calverley, P. M.] Aintree Univ Hosp NHS Fdn Trust, Liverpool, Merseyside, England. [Similowski, T.] Grp Hosp Pitie Salpetriere, Serv Pneumol, Paris, France. [Eriksson, G. S.; Fageras, M.; Persson, A.] AstraZeneca R&D, Molndal, Sweden. [Jenkins, C. R.] Concord Hosp, Concord, NSW, Australia. [Anzueto, A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Anzueto, A.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Make, B. J.] Univ Colorado, Natl Jewish Hlth, Denver, CO 80202 USA. [Postma, D.] Univ Groningen, Univ Med Ctr Groningen, GRIAC Res Inst, Groningen, Netherlands. NR 3 TC 1 Z9 1 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A4278 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838400713 ER PT J AU Campbell, JD Luo, L Liu, G Xiao, J Gerrein, J Guardela, B Tedrow, JR Aleksyev, Y Yang, IV Correll, M Geraci, MW Quackenbush, J Sciurba, FC Schwartz, DA Kaminski, N Lenburg, M Beane, J Spira, A AF Campbell, J. D. Luo, L. Liu, G. Xiao, J. Gerrein, J. Guardela, B. Tedrow, J. R. Aleksyev, Y. Yang, I. V. Correll, M. Geraci, M. W. Quackenbush, J. Sciurba, F. C. Schwartz, D. A. Kaminski, N. Lenburg, M. Beane, J. Spira, A. TI Characterizing The Small Rna Transcriptome Associated With COPD And Ild Using Next Generation Sequencing SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Campbell, J. D.; Luo, L.; Liu, G.; Xiao, J.; Gerrein, J.; Aleksyev, Y.; Lenburg, M.; Beane, J.; Spira, A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Guardela, B.; Tedrow, J. R.; Sciurba, F. C.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Yang, I. V.; Schwartz, D. A.] Natl Jewish Hlth, Denver, CO USA. [Correll, M.; Quackenbush, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Geraci, M. W.] Univ Colorado, Aurora, CO USA. [Kaminski, N.] Univ Pittsburgh, Pittsburgh, PA USA. EM camp@bu.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A4738 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838401381 ER PT J AU Campo, M Rimland, D Wongtrakool, C Hoo, GS Goetz, MB Brown, S Kim, JW Huang, L Rodriguez-Barradas, M Akgun, KM Crothers, KA AF Campo, M. Rimland, D. Wongtrakool, C. Hoo, G. Soo Goetz, M. B. Brown, S. Kim, J. W. Huang, L. Rodriguez-Barradas, M. Akgun, K. M. Crothers, K. A. TI Is Hepatitis C Infection Associated With Impairment In Lung Function? SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Campo, M.; Crothers, K. A.] Univ Washington, Seattle, WA 98195 USA. [Rimland, D.; Wongtrakool, C.] Atlanta Vet Affairs Med Ctr, Decatur, GA USA. [Hoo, G. Soo; Goetz, M. B.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Brown, S.; Kim, J. W.] James J Peters VA Med Ctr, Bronx, NY USA. [Huang, L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Huang, L.] San Francisco Gen Hosp, San Francisco, CA 94110 USA. [Rodriguez-Barradas, M.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Akgun, K. M.] Yale Univ, New Haven, CT USA. EM mcampo@uw.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A4240 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838400675 ER PT J AU Channick, RN Delcroix, M Galie, N Ghofrani, HA Hunsche, E Jansa, P Le Brun, FO Mehta, S Mittelholzer, C Perchenet, L Pulido, T Sastry, B Sitbon, O Souza, R Torbicki, A Rubin, LJ Simonneau, G AF Channick, R. N. Delcroix, M. Galie, N. Ghofrani, H. -A. Hunsche, E. Jansa, P. Le Brun, F. -O. Mehta, S. Mittelholzer, C. Perchenet, L. Pulido, T. Sastry, B. Sitbon, O. Souza, R. Torbicki, A. Rubin, L. J. Simonneau, G. TI Macitentan Reduces Pah-Related Hospitalizations: Results From The Randomized Controlled Seraphin Trial SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Channick, R. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Delcroix, M.] Univ Hosp Gasthuisberg, Leuven, Belgium. [Galie, N.] Univ Bologna, Bologna, Italy. [Ghofrani, H. -A.] Univ Hosp Giessen, Giessen, Germany. [Hunsche, E.; Le Brun, F. -O.; Mittelholzer, C.; Perchenet, L.] Actel Pharmaceut Ltd, Allschwil, Switzerland. [Jansa, P.] Charles Univ Prague, Prague, Czech Republic. [Mehta, S.] Western Univ, Victoria Hosp, London Hlth Sci Ctr, London, ON, Canada. [Pulido, T.] Natl Inst Cardiol, Mexico City, DF, Mexico. [Sastry, B.] CARE Hosp, Hyderabad, Andhra Pradesh, India. [Sitbon, O.; Simonneau, G.] Univ Paris Sud, Hop Univ Bicetre, Le Kremlin Bicetre, France. [Souza, R.] Univ Sao Paulo, Sch Med, Heart Inst, Sao Paulo, Brazil. [Torbicki, A.] ECZ Otwock, Ctr Postgrad Med Educ, Otwock, Poland. [Rubin, L. J.] Univ Calif San Diego, San Diego, CA 92103 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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. PY 2013 VL 187 MA A3527 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839103100 ER PT J AU Choy, E Staddon, A Alcindor, T Ferrari, S Engellau, J Rutkowski, P Feng, A Jacobs, I AF Choy, E. Staddon, A. Alcindor, T. Ferrari, S. Engellau, J. Rutkowski, P. Feng, A. Jacobs, I. TI Denosumab Treatment For Giant Cell Tumor Metastatic To The Lung SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Choy, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Staddon, A.] Penn Oncol Hematol Associates, Philadelphia, PA USA. [Alcindor, T.] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Ferrari, S.] Ist Ortoped Rizzoli, Bologna, Italy. [Engellau, J.] Skane Univ Sjukhus, Lund, Sweden. [Rutkowski, P.] Inst Im Marii Sklodowskiej Curie, Ctr Onkol, Warsaw, Poland. [Feng, A.; Jacobs, I.] Amgen Inc, Thousand Oaks, CA 91320 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A3600 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838400053 ER PT J AU Cloonan, SM Lam, HC Mizumura, K Haspel, JA Parameswaran, H Glass, K Quackenbusch, J Ryter, S Demeo, DL Silverman, EK Choi, AMK AF Cloonan, S. M. Lam, H. C. Mizumura, K. Haspel, J. A. Parameswaran, H. Glass, K. Quackenbusch, J. Ryter, S. Demeo, D. L. Silverman, E. K. Choi, A. M. K. TI Autophagy Controls The Clearance Of The COPD Susceptibility Gene Ireb2 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Cloonan, S. M.; Lam, H. C.; Mizumura, K.; Haspel, J. A.; Ryter, S.; Choi, A. M. K.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA. [Parameswaran, H.] Boston Univ, Boston, MA 02215 USA. [Glass, K.; Quackenbusch, J.] Harvard Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA USA. [Demeo, D. L.; Silverman, E. K.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A5170 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838401804 ER PT J AU Collins, BF Ramenofsky, D Au, DH Uman, JE Ma, J Feemster, LM AF Collins, B. F. Ramenofsky, D. Au, D. H. Uman, J. E. Ma, J. Feemster, L. M. TI The Association Of Weight With The Detection Of Airflow Obstruction And Inhaled Treatment Among Patients With A Clinical Diagnosis Of Chronic Obstructive Pulmonary Disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Collins, B. F.; Ramenofsky, D.] Univ Washington, Seattle, WA 98195 USA. [Au, D. H.; Feemster, L. M.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Uman, J. E.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Ma, J.] Palo Alto Med Fdn Res Inst, Palo Alto, CA USA. [Ma, J.] Stanford Univ, Sch Med, Stanford Prevent Res Ctr, Palo Alto, CA 94304 USA. EM bfc3@uw.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A2843 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839102232 ER PT J AU Cooke, CR Feemster, LC Wiener, RS Slatore, CG AF Cooke, C. R. Feemster, L. C. Wiener, R. S. Slatore, C. G. TI Intensive Care Unit Utilization Among Patients With Lung Cancer In The Seer-Medicare Registry SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Cooke, C. R.] Univ Michigan, Ann Arbor, MI 48109 USA. [Feemster, L. C.] Univ Washington, Seattle, WA 98195 USA. [Wiener, R. S.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Slatore, C. G.] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A2141 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839101313 ER PT J AU De Aguiar, MAM Gros, A Bar-Yam, Y Venegas, JG Winkler, T AF De Aguiar, M. A. M. Gros, A. Bar-Yam, Y. Venegas, J. G. Winkler, T. TI What Causes Airway Instability And Ventilation Defects During Bronchoconstriction In Asthma? SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [De Aguiar, M. A. M.] Univ Estadual Campinas, Campinas, SP, Brazil. [Gros, A.; Bar-Yam, Y.] New England Complex Syst Inst, Cambridge, MA USA. [Venegas, J. G.; Winkler, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Venegas, J. G.; Winkler, T.] Harvard Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A4013 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838400450 ER PT J AU Depp, TB McGinnis, K Kraemer, K Fiellin, DA Butt, AA Crystal, S Gordon, AJ Akgun, KM Gibert, C Edelman, EJ Bryant, KJ Crothers, KA AF Depp, T. B. McGinnis, K. Kraemer, K. Fiellin, D. A. Butt, A. A. Crystal, S. Gordon, A. J. Akgun, K. M. Gibert, C. Edelman, E. J. Bryant, K. J. Crothers, K. A. CA Vet Aging Cohort Study TI Hiv And Risk For Acute Exacerbation Of COPD SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Depp, T. B.; Kraemer, K.; Butt, A. A.] Univ Pittsburgh, Pittsburgh, PA USA. [McGinnis, K.; Gordon, A. J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Fiellin, D. A.; Akgun, K. M.; Edelman, E. J.] Yale Sch Med, New Haven, CT USA. [Crystal, S.] Rutgers State Univ, New Brunswick, NJ USA. [Gibert, C.] Washington DC VA Med Ctr, Washington, DC USA. [Bryant, K. J.] NIH, Bethesda, MD 20892 USA. [Crothers, K. A.] Univ Washington, Seattle, WA 98195 USA. EM depp.timothy@medstudent.pitt.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A2489 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839101660 ER PT J AU Dudley, KA Seiger, AN Tavakkoli, A Andrews, RA Patel, SR AF Dudley, K. A. Seiger, A. N. Tavakkoli, A. Andrews, R. A. Patel, S. R. TI Interest In Bariatric Surgery Among Obstructive Sleep Apnea Patients SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Dudley, K. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Seiger, A. N.; Tavakkoli, A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Andrews, R. A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Patel, S. R.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A5686 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838402454 ER PT J AU Everett, CK Benator, D Davis, JL Alland, D Heilig, C Persing, DH Tenover, FC Weiner, M Kerrigan, A Zamudio, C Whitworth, WC Goldberg, SV Nahid, P AF Everett, C. K. Benator, D. Davis, J. L. Alland, D. Heilig, C. Persing, D. H. Tenover, F. C. Weiner, M. Kerrigan, A. Zamudio, C. Whitworth, W. C. Goldberg, S. V. Nahid, P. TI Automated Quantitative Pcr Using Xpert (R) Mtb/rif To Monitor Tuberculosis Treatment SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Everett, C. K.; Davis, J. L.; Nahid, P.] UCSF SFGH, San Francisco, CA USA. [Benator, D.] US Dept Vet Affairs, Washington, DC USA. [Alland, D.] Univ Med & Dent New Jersey, Newark, NJ 07103 USA. [Heilig, C.; Goldberg, S. V.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Persing, D. H.; Tenover, F. C.] Cepheid Inc, Sunnyvale, CA USA. [Weiner, M.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Kerrigan, A.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Zamudio, C.] Univ Peruana Cayetano Heredia, Lima, Peru. [Whitworth, W. C.] CDC, Atlanta, GA 30333 USA. EM Charles.Everett@ucsf.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A3180 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839102569 ER PT J AU Everhart, RS Mitchell, DK McQuaid, E Friedman, D Canino, G Fritz, G AF Everhart, R. S. Mitchell, D. Koinis McQuaid, E. Friedman, D. Canino, G. Fritz, G. TI Pediatric Asthma Management Within Latino And Non-Latino White Families SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Everhart, R. S.] Virginia Commonwealth Univ, Richmond, VA USA. [Mitchell, D. Koinis; McQuaid, E.; Fritz, G.] Rhode Isl Hosp, Brown Med Sch, Providence, RI USA. [Friedman, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Canino, G.] Univ Puerto Rico, Rio Piedras, PR USA. EM reverhart@vcu.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A4951 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838401594 ER PT J AU Falcao, LR Wellman, TJ De Prost, N Winkler, T Musch, G Costa, ELV Tucci, MR Harris, RS Venegas, JG Melo, MFV AF Falcao, L. R. Wellman, T. J. De Prost, N. Winkler, T. Musch, G. Costa, E. L. V. Tucci, M. R. Harris, R. S. Venegas, J. G. Melo, M. F. Vidal TI Cluster Analysis Of The Pulmonary Kinetics Of 2-[fluorine-18]-Fluoro-2-Deoxy-D-Glucose In Models Of Acute Lung Injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Falcao, L. R.; Wellman, T. J.; Winkler, T.; Musch, G.; Harris, R. S.; Venegas, J. G.; Melo, M. F. Vidal] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [De Prost, N.] Hop Henri Mondor, Hop Paris, Paris, France. [Costa, E. L. V.; Tucci, M. R.] Univ Sao Paulo, Sao Paulo, Brazil. EM luizfernandofalcao@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A4902 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838401545 ER PT J AU Feemster, LMC Collins, BF Uman, J Au, DH AF Feemster, L. M. Cecere Collins, B. F. Uman, J. Au, D. H. TI Factors Explaining Variation In Dyspnea, Health-Related Quality Of Life, And Medication Use Among Veterans With COPD SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Feemster, L. M. Cecere; Collins, B. F.; Au, D. H.] Univ Washington, VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98195 USA. [Uman, J.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. EM lcecere@u.washington.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A5699 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838402467 ER PT J AU Feemster, LMC Ma, J McBurnie, MA Carson, SS Henderson, AG Lee, TA Lindenauer, PK Mularski, RA Naureckas, ET Vollmer, WM Krishnan, JA Au, DH AF Feemster, L. M. Cecere Ma, J. McBurnie, M. A. Carson, S. S. Henderson, A. G. Lee, T. A. Lindenauer, P. K. Mularski, R. A. Naureckas, E. T. Vollmer, W. M. Krishnan, J. A. Au, D. H. CA CONCERT Consortium TI The Association Of Body Mass Index And Waist Circumference With Six-Minute Walk Distance And Symptoms Among Patients With COPD SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Feemster, L. M. Cecere; Au, D. H.] Univ Washington, VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98195 USA. [Ma, J.] Stanford Univ, Sch Med, Palo Alto Med Fdn Res Inst, Dept Hlth Serv Res, Palo Alto, CA 94304 USA. [Ma, J.] Stanford Univ, Sch Med, Stanford Prevent Res Ctr, Palo Alto, CA 94304 USA. [McBurnie, M. A.; Mularski, R. A.; Vollmer, W. M.] Kaiser Permanente Northwest, Ctr Hlth Res, Portland, OR USA. [Carson, S. S.; Henderson, A. G.] Univ North Carolina Chapel Hill, Chapel Hill, NC USA. [Lee, T. A.; Krishnan, J. A.] Univ Illinois, Chicago, IL USA. [Lindenauer, P. K.] Baystate Med Ctr, Ctr Qual Care Res, Springfield, MA USA. [Naureckas, E. T.] Univ Chicago, Dept Med, Sect Pulm & Crit Care, Chicago, IL 60637 USA. EM lcecere@u.washington.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838401655 ER PT J AU Feemster, LMC Parsons, EC Crothers, KA Plumley, R Collins, MP Moss, B Udris, EM Au, DH AF Feemster, L. M. Cecere Parsons, E. C. Crothers, K. A. Plumley, R. Collins, M. P. Moss, B. Udris, E. M. Au, D. H. TI The Association Of Body Mass Index With Icu Admission And Mechanical Ventilation Among Veterans Hospitalized With An Exacerbation Of COPD SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Feemster, L. M. Cecere; Parsons, E. C.; Au, D. H.] Univ Washington, Hlth Serv Res & Dev, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Crothers, K. A.] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. [Plumley, R.; Collins, M. P.; Moss, B.; Udris, E. M.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. EM lcecere@u.washington.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839102426 ER PT J AU Gaffin, JM Petty, CR Sheehan, WJ Baxi, SN Permaul, P Kopel, LS Fu, C Kanchongkittiphon, W Gold, DR Phipatanakul, W AF Gaffin, J. M. Petty, C. R. Sheehan, W. J. Baxi, S. N. Permaul, P. Kopel, L. S. Fu, C. Kanchongkittiphon, W. Gold, D. R. Phipatanakul, W. TI Classroom-Based Air Pollution Effects On Asthma Morbidity In Inner City School Children SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Gaffin, J. M.; Petty, C. R.; Sheehan, W. J.; Baxi, S. N.; Kopel, L. S.; Kanchongkittiphon, W.; Phipatanakul, W.] Boston Childrens Hosp, Boston, MA USA. [Permaul, P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fu, C.; Gold, D. R.] Channing Labs, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A2521 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839101692 ER PT J AU Garcia-Bellmunt, L Solanes, I Mateus, E Torrego, A Giner, J Restrepo, MI Anzueto, A Sibila, O AF Garcia-Bellmunt, L. Solanes, I. Mateus, E. Torrego, A. Giner, J. Restrepo, M. I. Anzueto, A. Sibila, O. TI Role Of Mucins In Bacterial Colonization In COPD SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Garcia-Bellmunt, L.; Solanes, I.; Mateus, E.; Torrego, A.; Giner, J.; Sibila, O.] Hosp Santa Creu & Sant Pau, Barcelona, Spain. [Restrepo, M. I.] UTHSCSA, San Antonio, TX USA. [Restrepo, M. I.] South Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. [Anzueto, A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Anzueto, A.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. EM osibila@santpau.cat NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A2176 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839101348 ER PT J AU Gilpin, SE Guyette, J Wu, S Ren, X Gonzalez, G Vacanti, JP Ott, H AF Gilpin, S. E. Guyette, J. Wu, S. Ren, X. Gonzalez, G. Vacanti, J. P. Ott, H. TI Generation Of Acellular Pig And Human Lung Scaffolds For Whole Organ Regeneration SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Gilpin, S. E.; Guyette, J.; Wu, S.; Ren, X.; Gonzalez, G.; Vacanti, J. P.; Ott, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM sgilpin@partners.org NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A4990 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838401624 ER PT J AU Golnabi, AH Winkler, T Venegas, JG AF Golnabi, A. H. Winkler, T. Venegas, J. G. TI Synergistic Effects Of Deep Breath Volume And Frequency On Bronchoconstriction SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Golnabi, A. H.; Winkler, T.; Venegas, J. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Golnabi, A. H.; Winkler, T.; Venegas, J. G.] Harvard Med Sch, Boston, MA USA. EM Golnabi.Amir@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A4023 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838400460 ER PT J AU Greenblatt, EE Harris, RS Winkler, T Kelly, VJ Kone, M Katz, I Martin, AR Montesantos, S Caillibotte, G Venegas, JG AF Greenblatt, E. E. Harris, R. S. Winkler, T. Kelly, V. J. Kone, M. Katz, I. Martin, A. R. Montesantos, S. Caillibotte, G. Venegas, J. G. TI Relationship Between Regional Ventilation And Aerosol Deposition In Bronchoconstricted Subjects With Asthma SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Greenblatt, E. E.; Harris, R. S.; Winkler, T.; Kelly, V. J.; Kone, M.; Venegas, J. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Greenblatt, E. E.] MIT, Boston, MA USA. [Harris, R. S.; Winkler, T.; Kelly, V. J.; Kone, M.; Venegas, J. G.] Harvard Med Sch, Boston, MA USA. [Katz, I.; Martin, A. R.; Montesantos, S.; Caillibotte, G.] Air Liquide R&D, Jouy En Josas, France. EM eeg@mit.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A4027 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838400464 ER PT J AU Greenland, J Jewell, N Golden, J Caughey, G AF Greenland, J. Jewell, N. Golden, J. Caughey, G. TI Bronchoalveolar Lavage Cell Profiles Predict Acute Lung Allograft Rejection SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Greenland, J.; Caughey, G.] San Francisco VA Med Ctr, San Francisco, CA USA. [Jewell, N.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Golden, J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A2187 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839101359 ER PT J AU Grissom, CK Dickerson, JB Hirshberg, E Lanspa, MJ Schoenfeld, D Morris, AH AF Grissom, C. K. Dickerson, J. B. Hirshberg, E. Lanspa, M. J. Schoenfeld, D. Morris, A. H. CA NIH NHLBI ARDS Network TI Retrospective Comparison Of A Simpler Modified Fluid Conservative Protocol With The Original Factt Fluid Conservative Protocol In The Ards Network SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Grissom, C. K.; Dickerson, J. B.; Hirshberg, E.; Lanspa, M. J.; Morris, A. H.] Intermt Med Ctr, Murray, UT USA. [Schoenfeld, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM colin.grissom@imail.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A4482 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838401125 ER PT J AU Hardin, CC Manomohan, G Tambe, D Dubrovskyi, O Birukov, KG Butler, JP Fredberg, JJ Krishnan, R AF Hardin, C. C. Manomohan, G. Tambe, D. Dubrovskyi, O. Birukov, K. G. Butler, J. P. Fredberg, J. J. Krishnan, R. TI Intercellular Shear Destabilizes The Cell-Cell Junction In Models Of Acute Lung Injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Hardin, C. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Manomohan, G.; Krishnan, R.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Tambe, D.; Fredberg, J. J.] Harvard Sch Publ Hlth, Boston, MA USA. [Dubrovskyi, O.; Birukov, K. G.] Univ Chicago, Chicago, IL 60637 USA. [Butler, J. P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Butler, J. P.] Harvard Med Sch, Boston, MA USA. EM CHARDIN@PARTNERS.ORG NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A2102 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839101274 ER PT J AU Henderson, WR Dominelli, PB Griesdale, DE Talmor, DS Sheel, AW AF Henderson, W. R. Dominelli, P. B. Griesdale, D. E. Talmor, D. S. Sheel, A. W. TI Airway Pressure Does Not Predict Transpulmonary Pressure During High Frequency Oscillation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society CY MAY 17-22, 2013 CL Philadelphia, PA SP Amer Thorac Soc C1 [Henderson, W. R.; Griesdale, D. E.] Vancouver Gen Hosp, Vancouver, BC, Canada. [Dominelli, P. B.; Sheel, A. W.] Univ British Columbia, Vancouver, BC, Canada. [Talmor, D. S.] BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A1131 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839100113 ER PT J AU Hibbert, KA Winkler, T Melo, MFV Harris, RS Kelly, VJ Wellman, TJ De Castro, AK Venegas, JG Musch, G AF Hibbert, K. A. Winkler, T. Melo, M. F. Vidal Harris, R. S. Kelly, V. J. Wellman, T. J. De Castro, A. K. Venegas, J. G. Musch, G. TI Effect Of Early Prone Positioning On Shunt, Gas Fraction Distribution And Inflammatory Cell Metabolic Activity In A Sheep Model Of Ards SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society CY MAY 17-22, 2013 CL Philadelphia, PA SP Amer Thorac Soc C1 [Hibbert, K. A.; Winkler, T.; Melo, M. F. Vidal; Harris, R. S.; Kelly, V. J.; De Castro, A. K.; Venegas, J. G.; Musch, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hibbert, K. A.; Winkler, T.; Melo, M. F. Vidal; Harris, R. S.; Kelly, V. J.; De Castro, A. K.; Venegas, J. G.; Musch, G.] Harvard Med Sch, Boston, MA USA. [Wellman, T. J.] Boston Univ, Boston, MA 02215 USA. EM kahibbert@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A1133 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839100115 ER PT J AU Hickey, GA Keith, RL Nemenoff, R Franklin, W Sugita, M Geraci, MW Edwards, MG Merrick, DT AF Hickey, G. A. Keith, R. L. Nemenoff, R. Franklin, W. Sugita, M. Geraci, M. W. Edwards, M. G. Merrick, D. T. TI Utilizing Pathway Analysis To Develop Chemoprevention Strategies For Lung Cancer SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Hickey, G. A.; Nemenoff, R.; Franklin, W.; Sugita, M.; Geraci, M. W.; Edwards, M. G.] Univ Colorado Denver, Aurora, CO USA. [Keith, R. L.; Merrick, D. T.] Denver VA Med Ctr, Denver, CO USA. EM gregory.hickey@ucdenver.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A4754 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838401397 ER PT J AU Hsieh, SJ Zhuo, H Benowitz, NL Thompson, BT Liu, K Matthay, MA Calfee, CS AF Hsieh, S. J. Zhuo, H. Benowitz, N. L. Thompson, B. T. Liu, K. Matthay, M. A. Calfee, C. S. TI Smokers With Ards Have Equivalent Severity Of Lung Injury As Nonsmokers, Despite Lower Severity Of Illness And Fewer Comorbidities SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Hsieh, S. J.] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. [Zhuo, H.; Benowitz, N. L.; Liu, K.; Matthay, M. A.; Calfee, C. S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Thompson, B. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM shsieh@montefiore.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A2225 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839101397 ER PT J AU Kadri, S Hohmann, S Palmore, T Christopher, KB Varughese, C Danner, RL AF Kadri, S. Hohmann, S. Palmore, T. Christopher, K. B. Varughese, C. Danner, R. L. TI Trends In Intravenous Colistin Use As A Marker Of Rise In Multidrug Resistant Gram-Negative Infections At Academic Medical Centers In The U.s SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Kadri, S.; Palmore, T.; Danner, R. L.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Hohmann, S.] Univ HealthSyst Consortium, Chicago, IL USA. [Christopher, K. B.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA. [Varughese, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM sameer.kadri@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A3067 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839102456 ER PT J AU Keene, J Van Koeverden, I Elicker, B Stoel, BC Gold, WM Arjomandi, M AF Keene, J. Van Koeverden, I. Elicker, B. Stoel, B. C. Gold, W. M. Arjomandi, M. TI Chronic Exposure To Secondhand Tobacco Smoke Is Associated With Radiographic Air Trapping In Lung SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Keene, J.; Van Koeverden, I.; Elicker, B.; Gold, W. M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Stoel, B. C.] Leiden Univ, Med Ctr, Leiden, Netherlands. [Arjomandi, M.] San Francisco VA Med Ctr, San Francisco, CA USA. EM mehrdad.arjomandi@ucsf.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A3731 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838400184 ER PT J AU Kelly, VJ Winkler, T Venegas, JG Wongviriyawong, C Kone, M Greenblatt, EE Hibbert, KA Gladysheva, E Melo, MFV Musch, G Harris, RS AF Kelly, V. J. Winkler, T. Venegas, J. G. Wongviriyawong, C. Kone, M. Greenblatt, E. E. Hibbert, K. A. Gladysheva, E. Melo, M. F. Vidal Musch, G. Harris, R. S. TI The Contribution Of Hypoxic Pulmonary Vasoconstriction And Regional Hyperinflation To Reduced Perfusion In Poorly Ventilated Lung Regions During Bronchoconstiction In Asthma SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Kelly, V. J.; Winkler, T.; Venegas, J. G.; Wongviriyawong, C.; Kone, M.; Greenblatt, E. E.; Hibbert, K. A.; Gladysheva, E.; Melo, M. F. Vidal; Musch, G.; Harris, R. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kelly, V. J.; Winkler, T.; Venegas, J. G.; Wongviriyawong, C.; Kone, M.; Greenblatt, E. E.; Hibbert, K. A.; Gladysheva, E.; Melo, M. F. Vidal; Musch, G.; Harris, R. S.] Harvard Med Sch, Boston, MA USA. EM vanessajanekelly@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A4032 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838400469 ER PT J AU Kelly, VJ Winkler, T Venegas, JG Kone, M Greenblatt, EE Hibbert, KA Gladysheva, E Melo, MFV Musch, G Harris, RS AF Kelly, V. J. Winkler, T. Venegas, J. G. Kone, M. Greenblatt, E. E. Hibbert, K. A. Gladysheva, E. Melo, M. F. Vidal Musch, G. Harris, R. S. TI Effect Of Hyperoxia On Perfusion Within Poorly Ventilating Lung Regions In Adults With Asthma During Mannitol Induced Bronchoconstriction SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Kelly, V. J.; Winkler, T.; Venegas, J. G.; Kone, M.; Greenblatt, E. E.; Hibbert, K. A.; Gladysheva, E.; Melo, M. F. Vidal; Musch, G.; Harris, R. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kelly, V. J.; Winkler, T.; Venegas, J. G.; Kone, M.; Hibbert, K. A.; Gladysheva, E.; Melo, M. F. Vidal; Musch, G.; Harris, R. S.] Harvard Med Sch, Boston, MA USA. [Greenblatt, E. E.] MIT, Boston, MA USA. EM vjkelly@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A1936 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839101118 ER PT J AU Kim, YS Kleerup, E Needleman, J Lorenz, K AF Kim, Y. S. Kleerup, E. Needleman, J. Lorenz, K. TI Utilization, Cost, And Outcomes Of Medicare Patients Admitted To Long Term Care Hospitals (ltch) With Prolonged Mechanical Ventilation (pmv) SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Kim, Y. S.; Kleerup, E.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Needleman, J.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Lorenz, K.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. EM ykim@mednet.ucla.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839101311 ER PT J AU Kinsey, CM Estepar, RSJ Zhao, Y Yu, X Heist, RS Wain, J Washko, GR Christiani, DC AF Kinsey, C. M. Estepar, R. S. J. Zhao, Y. Yu, X. Heist, R. S. Wain, J. Washko, G. R. Christiani, D. C. TI Adenocarcinoma Occurs Predominantly In The Upper Regions Of The Lung And Is Associated With Improved Survival Compared To Occurrence In Other Regions SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Kinsey, C. M.; Heist, R. S.; Wain, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kinsey, C. M.] Harvard Med Sch, Boston, MA USA. [Estepar, R. S. J.; Washko, G. R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Zhao, Y.; Yu, X.; Christiani, D. C.] Harvard Sch Publ Hlth, Boston, MA USA. EM ckinsey@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A3604 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838400057 ER PT J AU Kradin, RL Bledsoe, J Christiani, DC AF Kradin, R. L. Bledsoe, J. Christiani, D. C. TI Smoking Related Fibrosis Confounds The Clinical Diagnosis Of Pulmonary Asbestosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Kradin, R. L.; Bledsoe, J.; Christiani, D. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM rkradin@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A4499 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838401142 ER PT J AU Kradin, RL Nishino, M Matthai, S Digumarthy, S AF Kradin, R. L. Nishino, M. Matthai, S. Digumarthy, S. TI Intralveolar Fibrin Predicts Clinical Relapse In Patients With Cryptogenic Organziing Pneumonia SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society CY MAY 17-22, 2013 CL Philadelphia, PA SP Amer Thorac Soc C1 [Kradin, R. L.; Nishino, M.; Matthai, S.; Digumarthy, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM rkradin@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A1074 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839100057 ER PT J AU Kunisaki, KM Crothers, K Fiellin, DA Gibert, CL Kim, JW Rimland, D Rodriguez-Barradas, MC Yaggi, HK Akgun, KM AF Kunisaki, K. M. Crothers, K. Fiellin, D. A. Gibert, C. L. Kim, J. W. Rimland, D. Rodriguez-Barradas, M. C. Yaggi, H. K. Akgun, K. M. TI Obstructive Sleep Apnea (osa) In A Cohort Of Hiv-Infected And Uninfected Veterans SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Kunisaki, K. M.] Minneapolis VA Healthcare Syst, Minneapolis, MN USA. [Crothers, K.] Univ Washington, Seattle, WA 98195 USA. [Fiellin, D. A.; Yaggi, H. K.] Yale Sch Med, New Haven, CT USA. [Gibert, C. L.] Washington DC Vet Affairs Med Ctr, Washington, DC USA. [Kim, J. W.] James J Peters VA Med Ctr, Bronx, NY USA. [Rimland, D.] Atlanta Vet Affairs Med Ctr, Atlanta, GA USA. [Rodriguez-Barradas, M. C.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Akgun, K. M.] VA Connecticut Healthcare Syst, West Haven, CT USA. EM kunis001@umn.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A2487 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839101658 ER PT J AU LaFemina, MJ Sweerus, K Gordon, ED Lachowicz-Scroggins, ME Bentley, T Sutherland, K Fahy, JV Frank, JA AF LaFemina, M. J. Sweerus, K. Gordon, E. D. Lachowicz-Scroggins, M. E. Bentley, T. Sutherland, K. Fahy, J. V. Frank, J. A. TI Does Claudin-18 Deficiency Contribute To Epithelial Barrier Dysfunction In Asthma? SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [LaFemina, M. J.; Frank, J. A.] UCSF, San Francisco VA Med Ctr, San Francisco, CA USA. [Sweerus, K.; Gordon, E. D.; Lachowicz-Scroggins, M. E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Bentley, T.] NCIRE San Francisco VA Med Ctr, San Francisco, CA USA. [Sutherland, K.] UCSF NCIRE, San Francisco, CA USA. [Fahy, J. V.] UCSF Biomed Sci Program, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A3562 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838400015 ER PT J AU Lai, PS Lin, X Zhang, FY Hang, JQ Christiani, DC AF Lai, P. S. Lin, X. Zhang, F. -Y. Hang, J. -Q. Christiani, D. C. TI The Effect Of Occupational Cotton Dust Exposure On Time To Development Of Impaired Lung Function And Death In Shanghai Textile Workers SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Lai, P. S.] Massachusetts Gen Hosp, Boston, MA USA. [Lin, X.; Christiani, D. C.] Harvard Sch Publ Hlth, Boston, MA USA. [Zhang, F. -Y.; Hang, J. -Q.] Shanghai Putuo Peoples Hosp, Shanghai, Peoples R China. EM plai@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A2076 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839101258 ER PT J AU Leroy, P Tenney, R Wong, H Silva, A Balmes, JR Arjomandi, M AF Leroy, P. Tenney, R. Wong, H. Silva, A. Balmes, J. R. Arjomandi, M. TI Molecular Insights From Human Airway Inflammatory Cell Messenger And Micro Rna Gene Expression After Ozone-Induced Oxidative Injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Leroy, P.; Tenney, R.; Silva, A.; Arjomandi, M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Wong, H.; Balmes, J. R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. EM mehrdad.arjomandi@ucsf.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A4736 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838401379 ER PT J AU LeVarge, BL Pomerantsev, E Channick, RN AF LeVarge, B. L. Pomerantsev, E. Channick, R. N. TI Misclassification Of Pulmonary Arterial Hypertension Patients Due To Overreliance On Wedge Pressure Measurement SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [LeVarge, B. L.; Pomerantsev, E.; Channick, R. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM blevarge@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A4698 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838401341 ER PT J AU LeVarge, BL Kradin, RL Wirth, JA Channick, RN AF LeVarge, B. L. Kradin, R. L. Wirth, J. A. Channick, R. N. TI Sarcoidosis With Pulmonary Venous Stenosis And Pulmonary Capillary Hemangiomatosis Mimicking Chronic Thromboembolic Pulmonary Hypertension SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [LeVarge, B. L.; Kradin, R. L.; Channick, R. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wirth, J. A.] Maine Med Ctr, Portland, ME 04102 USA. EM blevarge@partners.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A4593 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838401236 ER PT J AU Long, AA Rahmaoui, A Rothman, KJ Guinan, EC Eisner, MD Bradley, MS Iribarren, C Chen, H Carrigan, G Rosen, K Szefler, SJ AF Long, A. A. Rahmaoui, A. Rothman, K. J. Guinan, E. C. Eisner, M. D. Bradley, M. S. Iribarren, C. Chen, H. Carrigan, G. Rosen, K. Szefler, S. J. TI Incidence Of Malignancy In Omalizumab And Non-Omalizumab Treated Patients With Moderate-To-Severe Asthma: The Excels Study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Long, A. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rahmaoui, A.; Eisner, M. D.; Bradley, M. S.; Chen, H.; Carrigan, G.; Rosen, K.] Genentech Inc, San Francisco, CA 94080 USA. [Rothman, K. J.] RTI Hlth Solut, Res Triangle Pk, NC USA. [Guinan, E. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Iribarren, C.] Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94611 USA. [Szefler, S. J.] Natl Jewish Hlth, Denver, CO USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A3869 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838400306 ER PT J AU Ma, J Strub, P Camargo, CA Gardner, CD Wilson, SR Haskell, WL Buist, AS Lavori, PW Xiao, L AF Ma, J. Strub, P. Camargo, C. A. Gardner, C. D. Wilson, S. R. Haskell, W. L. Buist, A. S. Lavori, P. W. Xiao, L. TI A Behavioral Weight Loss Treatment Trial In Obese Adults With Uncontrolled Asthma: Recruitment, Patient Characteristics, And Retention SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Ma, J.; Wilson, S. R.] Palo Alto Med Fdn, Res Inst, Palo Alto, CA 94301 USA. [Strub, P.] Permanente Med Grp Inc, San Francisco, CA USA. [Camargo, C. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gardner, C. D.; Haskell, W. L.; Lavori, P. W.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Buist, A. S.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Xiao, L.] Palo Alto Med Fdn, Palo Alto, CA USA. EM xiaol@pamfri.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A5040 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838401674 ER PT J AU Martin, JL Zeidler, MR Omachi, TA Schneider, H Kleerup, E Badr, MS AF Martin, J. L. Zeidler, M. R. Omachi, T. A. Schneider, H. Kleerup, E. Badr, M. S. TI Sleep Quality Is An Independent Predictor Of Disease Specific Quality Of Life In COPD - Preliminary Findings Of The Spiromics Trial SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Martin, J. L.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, North Hills, CA USA. [Zeidler, M. R.; Kleerup, E.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Omachi, T. A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Schneider, H.] Johns Hopkins Med Sch, Baltimore, MD USA. [Badr, M. S.] John Dingell VAMC, Detroit, MI USA. [Badr, M. S.] Wayne State Univ, Detroit, MI USA. EM MZeidler@mednet.ucla.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A2891 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839102280 ER PT J AU Martin, S Goldberg, R Pinto-Plata, VM Divo, M Krinzman, S Tesfaigzi, Y Kelly, E Kroll-Desrosiers, A Owen, C Celli, BR AF Martin, S. Goldberg, R. Pinto-Plata, V. M. Divo, M. Krinzman, S. Tesfaigzi, Y. Kelly, E. Kroll-Desrosiers, A. Owen, C. Celli, B. R. TI Longitudinal Serum Biomarker Profile Change During Extended Smoking Cessation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Martin, S.; Krinzman, S.] Univ Massachusetts, Sch Med, Barre, MA USA. [Goldberg, R.; Kroll-Desrosiers, A.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Pinto-Plata, V. M.; Divo, M.; Owen, C.; Celli, B. R.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Pinto-Plata, V. M.; Divo, M.; Owen, C.; Celli, B. R.] Harvard Med Sch, Boston, MA USA. [Tesfaigzi, Y.] Lovelace Repiratory Res Inst, Albuquerque, NM USA. [Kelly, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM stephen.martin@umassmemorial.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A4090 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838400526 ER PT J AU Matura, L McDonough, A Carroll, D AF Matura, L. McDonough, A. Carroll, D. TI Symptom Burden And Health-Related Quality Of Life In Pulmonary Arterial Hypertension SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Matura, L.] Univ Penn, Philadelphia, PA 19104 USA. [McDonough, A.] Univ Massachusetts, Lowell, MA USA. [Carroll, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM matura@nursing.upenn.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A2502 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839101673 ER PT J AU McCannon, JB Currier, PF O'Donnell, WJ AF McCannon, J. B. Currier, P. F. O'Donnell, W. J. TI Readmissions Of The Chronic Critically Ill: A Retrospective Analysis Of "bounce Backs" From And Readmissions To A Post-Icu Unit Within A Major Teaching Hospital SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Currier, P. F.; O'Donnell, W. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A5324 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838402114 ER PT J AU McCarl, JD Koff, P Min, SJ Keith, RL Vandivier, RW AF McCarl, J. D. Koff, P. Min, S-J Keith, R. L. Vandivier, R. W. TI Exertional Hypoxemia Is Associated With Decreased Healthcare Utilization In Patients With Advanced Chronic Obstructive Pulmonary Disease On Long-Term Oxygen Therapy SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [McCarl, J. D.] Maine Med Ctr, Portland, ME 04102 USA. [Koff, P.; Min, S-J; Vandivier, R. W.] Univ Colorado, Aurora, CO USA. [Keith, R. L.] Univ Colorado, Denver Vet Affairs Med Ctr, Denver, CO 80202 USA. EM mccarj4@mmc.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A5564 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838402332 ER PT J AU Mealer, M Thompson, BT Oldmixon, C Wheeler, A Kahn, M Moss, M AF Mealer, M. Thompson, B. T. Oldmixon, C. Wheeler, A. Kahn, M. Moss, M. TI Remote Source Document Verification In The Nih Sponsored Ards Network: A Feasibility Study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Mealer, M.; Moss, M.] Univ Colorado, Aurora, CO USA. [Thompson, B. T.; Oldmixon, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wheeler, A.] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA. [Kahn, M.] Univ Colorado, Denver, CO 80202 USA. EM meredith.mealer@ucdenver.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A4476 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838401119 ER PT J AU Mehta, S Channick, RN Delcroix, M Galie, N Ghofrani, HA Hunsche, E Jansa, P Le Brun, FO Mittelholzer, C Perchenet, L Pulido, T Souza, R Sastry, B Torbicki, A Sitbon, O Rubin, LJ Simonneau, G AF Mehta, S. Channick, R. N. Delcroix, M. Galie, N. Ghofrani, H. -A. Hunsche, E. Jansa, P. Le Brun, F. -O. Mittelholzer, C. Perchenet, L. Pulido, T. Souza, R. Sastry, B. Torbicki, A. Sitbon, O. Rubin, L. J. Simonneau, G. TI Macitentan Improves Health-Related Quality Of Life In Pulmonary Arterial Hypertension: Results From The Randomized Controlled Seraphin Trial SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Mehta, S.] Western Univ, Victoria Hosp, London Hlth Sci Ctr, London, ON, Canada. [Channick, R. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Delcroix, M.] Univ Hosp Gasthuisberg, Leuven, Belgium. [Galie, N.] Univ Bologna, Bologna, Italy. [Ghofrani, H. -A.] Univ Hosp Giessen, Giessen, Germany. [Hunsche, E.; Le Brun, F. -O.; Mittelholzer, C.; Perchenet, L.] Actel Pharmaceut Ltd, Allschwil, Switzerland. [Jansa, P.] Charles Univ Prague, Prague, Czech Republic. [Pulido, T.] Natl Inst Cardiol, Mexico City, DF, Mexico. [Souza, R.] Univ Sao Paulo, Inst Heart, Sch Med, Sao Paulo, Brazil. [Sastry, B.] CARE Hosp, Hyderabad, Andhra Pradesh, India. [Torbicki, A.] ECZ Otwock, Ctr Postgrad Med Educ, Otwock, Poland. [Sitbon, O.; Simonneau, G.] Univ Paris Sud, Hop Univ Bicetre, Le Kremlin Bicetre, France. [Rubin, L. J.] Univ Calif San Diego, San Diego, CA 92103 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 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. PY 2013 VL 187 MA A3269 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839102658 ER PT J AU Mortensen, EM Halm, E Fine, M Anzueto, A AF Mortensen, E. M. Halm, E. Fine, M. Anzueto, A. TI Azithromycin Is Associated With Increased Cardiac Events But Lower Mortality For Patients Hospitalized With Pneumonia SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society CY MAY 17-22, 2013 CL Philadelphia, PA SP Amer Thorac Soc C1 [Mortensen, E. M.; Halm, E.] Univ Texas Southwestern Med Ctr Dallas, Dallas, TX 75390 USA. [Fine, M.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Anzueto, A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Anzueto, A.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A1144 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839100126 ER PT J AU Moschovis, PP Kleimola, LB Oreskovic, NM Campbell, RT Christiani, DC Hibberd, PL AF Moschovis, P. P. Kleimola, L. B. Oreskovic, N. M. Campbell, R. T. Christiani, D. C. Hibberd, P. L. TI Household Air Pollution And Risk Of Childhood Pneumonia Death In Low And Middle-Income Countries SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Moschovis, P. P.; Kleimola, L. B.; Oreskovic, N. M.; Hibberd, P. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Campbell, R. T.] Univ Illinois, Chicago, IL USA. [Christiani, D. C.] Harvard Sch Publ Hlth, Boston, MA USA. EM pmoschovis@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A5900 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838402659 ER PT J AU Mularski, RA McBurnie, M Schatz, M Krishnan, JA Puro, JE Williams, AE Millard, M Hu, WR Au, DH Hazlehurst, B AF Mularski, R. A. McBurnie, M. Schatz, M. Krishnan, J. A. Puro, J. E. Williams, A. E. Millard, M. Hu, W. R. Au, D. H. Hazlehurst, B. CA CER-HUB Asthma Grp TI Assessing Asthma Control Using Electronic Medical Record Data Across Six Health Care Service Sites SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Mularski, R. A.; McBurnie, M.; Hu, W. R.; Hazlehurst, B.] Kaiser Permanente Northwest, Ctr Hlth Res, Portland, OR USA. [Schatz, M.] Kaiser Permanente Southern Calif, San Diego, CA USA. [Krishnan, J. A.] Univ Illinois, Chicago, IL USA. [Puro, J. E.] OCHIN Inc, Portland, OR USA. [Williams, A. E.] Kaiser Permanente, Ctr Hlth Res Hawaii, Honolulu, HI USA. [Millard, M.] Baylor Univ, Med Ctr, Dallas, TX USA. [Au, D. H.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. EM richard.a.mularski@kpchr.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A5035 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838401669 ER PT J AU Nguyen, HQ Herting, J Adams, S Borson, S Kohen, R Matute-Bello, G Pagalilauan, G Fan, V AF Nguyen, H. Q. Herting, J. Adams, S. Borson, S. Kohen, R. Matute-Bello, G. Pagalilauan, G. Fan, V. CA CASCADE Study TI Identifying Latent Symptom Classes In Patients With Advanced COPD SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Nguyen, H. Q.] Kaiser Permanente Southern Calif, Pasadena, CA USA. [Herting, J.; Borson, S.; Kohen, R.; Pagalilauan, G.; Fan, V.] Univ Washington, Seattle, WA 98195 USA. [Adams, S.] Univ Texas San Antonio, San Antonio, TX USA. [Matute-Bello, G.] Univ Washington, Ctr Lung Biol, Seattle, WA 98195 USA. [Fan, V.] VA Puget Sound Hlth Care Syst, HSR&D, Seattle, WA USA. EM hqn@uw.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A2510 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839101681 ER PT J AU Novosad, SA Winthrop, KL Polgreen, PM Beekmann, SE Leitz, A Vu, T AF Novosad, S. A. Winthrop, K. L. Polgreen, P. M. Beekmann, S. E. Leitz, A. Vu, T. TI The Emerging Infections Network: Treatment Of Mycobacterium Abscessus And The Use Of Clofazimine SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Novosad, S. A.; Leitz, A.; Vu, T.] OHSU, Portland, OR USA. [Winthrop, K. L.] Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. [Polgreen, P. M.; Beekmann, S. E.] Univ Iowa, Iowa City, IA USA. EM novosad@ohsu.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A5110 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838401744 ER PT J AU Panchal, D Yuan, Z Rodgers, D Syed, M Schraufnagel, DE Christman, J Finn, P Sadikot, RT AF Panchal, D. Yuan, Z. Rodgers, D. Syed, M. Schraufnagel, D. E. Christman, J. Finn, P. Sadikot, R. T. TI Induction Of Cox-2 Signaling By S. Mucilaginous Highlights The Pathogenic Potential Of An Oral Commensal SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Panchal, D.; Rodgers, D.; Syed, M.; Christman, J.] US Dept Vet Affairs, Chicago, IL USA. [Yuan, Z.] US Dept Vet Affairs, Gainesville, FL USA. [Schraufnagel, D. E.; Finn, P.] Univ Illinois, Chicago, IL USA. [Sadikot, R. T.] Univ Florida, Gainesville, FL USA. EM rtsadikot@ufl.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A4542 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838401185 ER PT J AU Parsons, EC McFadden, CR Vitiello, MV Hough, CL Davydow, D AF Parsons, E. C. McFadden, C. R. Vitiello, M. V. Hough, C. L. Davydow, D. TI Validity Of A Single Ptsd Checklist Item To Screen For Insomnia In Survivors Of Critical Illness SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Parsons, E. C.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [McFadden, C. R.; Vitiello, M. V.; Hough, C. L.; Davydow, D.] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A3115 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839102504 ER PT J AU Parsons, EC Feemster, LM Plumley, R Collins, MP Moss, B Udris, EM Au, DH AF Parsons, E. C. Feemster, L. M. Plumley, R. Collins, M. P. Moss, B. Udris, E. M. Au, D. H. TI Association Of Corticosteroid Dose With Antipsychotic Use, Delirium, And Length Of Stay Among Veterans Hospitalized For COPD Exacerbation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Parsons, E. C.; Feemster, L. M.; Plumley, R.; Collins, M. P.; Moss, B.; Udris, E. M.; Au, D. H.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839100560 ER PT J AU Penuelas, O Frutos-Vivar, F Fan, E Ferguson, ND Thille, AW Rios, F Maggiore, SM Villagomez, A Gonzalez, M Nin, N Anzueto, A Esteban, A AF Penuelas, O. Frutos-Vivar, F. Fan, E. Ferguson, N. D. Thille, A. W. Rios, F. Maggiore, S. M. Villagomez, A. Gonzalez, M. Nin, N. Anzueto, A. Esteban, A. TI Incidence And Outcome Of Patients Diagnosed Of Icu-Acquired Weakness SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Penuelas, O.; Frutos-Vivar, F.; Esteban, A.] Hosp Univ Getafe, CIBERES, Getafe, Spain. [Fan, E.] Univ Toronto, Univ Hlth Network, Toronto, ON, Canada. [Ferguson, N. D.] Univ Toronto, Toronto, ON, Canada. [Thille, A. W.] Hosp Univ Getafe, Madrid, Spain. [Rios, F.] VENTILA Grp, Buenos Aires, DF, Argentina. [Maggiore, S. M.] VENTILA Grp, Rome, Italy. [Villagomez, A.] VENTILA Grp, Mexico City, DF, Mexico. [Gonzalez, M.] VENTILA Grp, Medellin, Colombia. [Nin, N.] VENTILA Grp, Madrid, Spain. [Anzueto, A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Anzueto, A.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. EM openuelas@gmail.com NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A3628 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838400081 ER PT J AU Pickard, AS Lee, TA Lin, F Au, DH McBurnie, MA Carson, SS Lindenauer, PK Mularski, RA Naureckas, ET Vollmer, WM Henderson, AG Krishnan, JA AF Pickard, A. S. Lee, T. A. Lin, F. Au, D. H. McBurnie, M. A. Carson, S. S. Lindenauer, P. K. Mularski, R. A. Naureckas, E. T. Vollmer, W. M. Henderson, A. G. Krishnan, J. A. CA CONCERT Consortium TI Measuring Health Using The Patient Reported Outcomes Measurement Information System (promis-43) In Chronic Obstructive Pulmonary Disease (COPD): Experience In The Concert Cohort SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Pickard, A. S.; Lee, T. A.; Lin, F.; Krishnan, J. A.] Univ Illinois, Chicago, IL USA. [Au, D. H.] Univ Washington, Seattle, WA 98195 USA. [Au, D. H.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [McBurnie, M. A.; Mularski, R. A.; Vollmer, W. M.] Kaiser Permanente Northwest Ctr Hlth Res, Portland, OR USA. [Carson, S. S.; Henderson, A. G.] Univ North Carolina Chapel Hill, Chapel Hill, NC USA. [Lindenauer, P. K.] Baystate Med Ctr, Boston, MA USA. [Lindenauer, P. K.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Naureckas, E. T.] Univ Chicago, Chicago, IL 60637 USA. EM flin6@uic.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A5037 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838401671 ER PT J AU Pickard, AS Lee, TA Lin, F Au, DH McBurnie, MA Carson, SS Lindenauer, PK Mularski, RA Naureckas, ET Vollmer, WM Henderson, AG Krishnan, JA AF Pickard, A. S. Lee, T. A. Lin, F. Au, D. H. McBurnie, M. A. Carson, S. S. Lindenauer, P. K. Mularski, R. A. Naureckas, E. T. Vollmer, W. M. Henderson, A. G. Krishnan, J. A. CA CONCERT Consortium TI Assessment Of Health-Related Quality Of Life Using Eq-5d-5l In Patients With Chronic Obstructive Pulmonary Disease (COPD): Experience In The Concert Cohort SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Pickard, A. S.; Lee, T. A.; Lin, F.; Krishnan, J. A.] Univ Illinois, Chicago, IL USA. [Au, D. H.] Univ Washington, Seattle, WA 98195 USA. [Au, D. H.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [McBurnie, M. A.; Mularski, R. A.; Vollmer, W. M.] Kaiser Permanente Northwest Ctr Hlth Res, Portland, OR USA. [Carson, S. S.; Henderson, A. G.] Univ N Carolina, Chapel Hill, NC USA. [Lindenauer, P. K.] Baystate Med Ctr, Boston, MA USA. [Lindenauer, P. K.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Naureckas, E. T.] Univ Chicago, Chicago, IL 60637 USA. EM flin6@uic.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A4224 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838400659 ER PT J AU Pickard, AS Lin, F Lee, TA Sharma, G Au, DH McBurnie, MA Carson, SS Lindenauer, PK Mularski, RA Naureckas, ET Vollmer, WM Henderson, AG Krishnan, JA AF Pickard, A. S. Lin, F. Lee, T. A. Sharma, G. Au, D. H. McBurnie, M. A. Carson, S. S. Lindenauer, P. K. Mularski, R. A. Naureckas, E. T. Vollmer, W. M. Henderson, A. G. Krishnan, J. A. CA CONCERT Consortium TI Evaluation Of The Functional Assessment Of The Chronic Illness Therapy (facit)-Dyspnea Short Form In Chronic Obstructive Pulmonary Disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Pickard, A. S.; Lin, F.; Lee, T. A.; Sharma, G.; Krishnan, J. A.] Univ Illinois, Chicago, IL USA. [Au, D. H.] Univ Washington, Seattle, WA 98195 USA. [Au, D. H.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [McBurnie, M. A.; Mularski, R. A.; Vollmer, W. M.] Kaiser Permanente Northwest Ctr Hlth Res, Portland, OR USA. [Carson, S. S.; Henderson, A. G.] Univ N Carolina, Chapel Hill, NC USA. [Lindenauer, P. K.] Baystate Med Ctr, Boston, MA USA. [Lindenauer, P. K.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Naureckas, E. T.] Univ Chicago, Chicago, IL 60637 USA. EM flin6@uic.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A4225 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838400660 ER PT J AU Pinto-Plata, VM Tesfaigzi, Y Divo, M Owen, C Petersen, H Wang, Y Holloway, D Sanchez, P Calhoun, V Martin, S Celli, BR AF Pinto-Plata, V. M. Tesfaigzi, Y. Divo, M. Owen, C. Petersen, H. Wang, Y. Holloway, D. Sanchez, P. Calhoun, V. Martin, S. Celli, B. R. TI Plasma Metabolic Profile In COPD Patients. Association To Survival SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Pinto-Plata, V. M.; Divo, M.; Owen, C.; Sanchez, P.; Celli, B. R.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Pinto-Plata, V. M.; Divo, M.; Owen, C.; Sanchez, P.; Celli, B. R.] Harvard Med Sch, Boston, MA USA. [Tesfaigzi, Y.; Petersen, H.] Lovelace Resp Res Inst, Albuquerque, NM USA. [Wang, Y.; Holloway, D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Calhoun, V.] Univ New Mexico, Albuquerque, NM 87131 USA. [Martin, S.] Univ Massachusetts, Barre, MA USA. EM vpinto-plata@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A1519 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839100501 ER PT J AU Plataki, M Malhotra, A Bajwa, E Bakker, JP Malinchoc, M Geeti, A Kaufman, DA AF Plataki, M. Malhotra, A. Bajwa, E. Bakker, J. P. Malinchoc, M. Geeti, A. Kaufman, D. A. CA Lung Injury Prevention Score Grp TI "normal" Blood Pressure In Sepsis: Relationship Between Hypotension And Mortality In Patients Presenting With Sepsis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Plataki, M.; Geeti, A.] Yale New Haven Hlth Syst, Bridgeport Hosp, Bridgeport, CT USA. [Malhotra, A.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA. [Bajwa, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bakker, J. P.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Bakker, J. P.] Harvard Med Sch, Boston, MA USA. [Malinchoc, M.] Mayo Clin, Rochester, MN USA. [Kaufman, D. A.] Yale Univ, Bridgeport Hosp, Bridgeport, CT USA. EM mplataki@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839102455 ER PT J AU Prekker, ME Feemster, LC Hough, CL Au, DH Crothers, KA Rea, TD Seymour, CW AF Prekker, M. E. Feemster, L. C. Hough, C. L. Au, D. H. Crothers, K. A. Rea, T. D. Seymour, C. W. TI The Epidemiology And Outcome Of Prehospital Respiratory Distress SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Prekker, M. E.; Hough, C. L.; Crothers, K. A.; Rea, T. D.] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. [Feemster, L. C.; Au, D. H.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Seymour, C. W.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. EM mprekker@uw.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A5295 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838402085 ER PT J AU Putcha, N Hansel, N Martinez, CH Han, MK Williams, AE Hersh, CP Wise, RA Thomashow, BM Hanania, NA Casaburi, R Kinney, GL Kim, YI Washko, GR Steiner, RM Anzueto, A Cho, MH Make, BJ Crapo, J Silverman, EK Regan, EA AF Putcha, N. Hansel, N. Martinez, C. H. Han, M. K. Williams, A. E. Hersh, C. P. Wise, R. A. Thomashow, B. M. Hanania, N. A. Casaburi, R. Kinney, G. L. Kim, Y. -I. Washko, G. R. Steiner, R. M. Anzueto, A. Cho, M. H. Make, B. J. Crapo, J. Silverman, E. K. Regan, E. A. CA COPDGene Investigators TI Comorbid Diseases In COPD Impacts Exercise Capacity, Quality Of Life And Dyspnea SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Putcha, N.; Hansel, N.] Johns Hopkins Univ, Baltimore, MD USA. [Martinez, C. H.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Han, M. K.] Univ Michigan, Ann Arbor, MI 48109 USA. [Williams, A. E.] UCL, London, England. [Hersh, C. P.; Washko, G. R.; Cho, M. H.; Silverman, E. K.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wise, R. A.] Johns Hopkins Med Ctr, Baltimore, MD USA. [Thomashow, B. M.] Columbia Univ, New York, NY USA. [Hanania, N. A.] Baylor Coll Med, Asthma Clin Res Ctr, Houston, TX 77030 USA. [Casaburi, R.] Harbor UCLA BRI, Torrance, CA USA. [Kinney, G. L.] Colorado Sch Publ Hlth, Aurora, CO USA. [Kim, Y. -I.] Chonnam Natl Univ Hosp, Natl Jewish Hlth, Denver, CO USA. [Steiner, R. M.] Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. [Anzueto, A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Anzueto, A.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Make, B. J.; Crapo, J.; Regan, E. A.] Natl Jewish Hlth, Denver, CO USA. [Silverman, E. K.] Harvard Med Sch, Boston, MA USA. EM nputcha1@jhmi.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A5697 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838402465 ER PT J AU Reddy, AT Lakshmi, SP Dornadula, S Pinni, S Rampa, DR Reddy, RC AF Reddy, A. T. Lakshmi, S. P. Dornadula, S. Pinni, S. Rampa, D. R. Reddy, R. C. TI Nitrated Fatty Acids Inhibit Allergic Airway Disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Reddy, A. T.; Lakshmi, S. P.; Dornadula, S.; Pinni, S.; Rampa, D. R.; Reddy, R. C.] Univ Pittsburgh, Sch Med, Dept Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15213 USA. [Reddy, A. T.; Lakshmi, S. P.; Dornadula, S.; Pinni, S.; Rampa, D. R.; Reddy, R. C.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. EM tarugua@upmc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A2657 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839102047 ER PT J AU Reinke, LF Feemster, LMC Uman, JE Au, DH AF Reinke, L. F. Feemster, L. M. Cecere Uman, J. E. Au, D. H. TI Assessment And Treatment Of Symptoms For Outpatients Newly Diagnosed With Lung Cancer SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Reinke, L. F.] Dept Vet Affairs, Edmonds, WA USA. [Feemster, L. M. Cecere] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Uman, J. E.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Au, D. H.] Univ Washington, VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98195 USA. EM reinkl@myuw.net NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A6034 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838403024 ER PT J AU Rice, MB Rifas-Shiman, S Litonjua, AA Oken, E Gillman, M Mittleman, MA Gold, D AF Rice, M. B. Rifas-Shiman, S. Litonjua, A. A. Oken, E. Gillman, M. Mittleman, M. A. Gold, D. TI Exposure To Traffic And Early Life Respiratory Infection: A Cohort Study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Rice, M. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rifas-Shiman, S.; Oken, E.; Gillman, M.] Harvard Med Sch, Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Litonjua, A. A.; Gold, D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Mittleman, M. A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. EM mrice2@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A3503 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839103076 ER PT J AU Rinne, ST Feemster, LM Collins, BF Au, DH Perkins, M Bryson, CL O'Riordan, T Liu, CF AF Rinne, S. T. Feemster, L. M. Collins, B. F. Au, D. H. Perkins, M. Bryson, C. L. O'Riordan, T. Liu, C. -F. TI Glitazones Are Associated With A Reduced Risk Of Asthma Exacerbation Among Patients With Diabetes SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Rinne, S. T.; Feemster, L. M.; Collins, B. F.; Au, D. H.; Perkins, M.; Bryson, C. L.; Liu, C. -F.] Univ Washington, Seattle, WA 98195 USA. [Feemster, L. M.; Au, D. H.; Perkins, M.; Bryson, C. L.; Liu, C. -F.] VA Puget Sound Hlth Care Syst, HSR&D, Seattle, WA USA. [O'Riordan, T.] Gilead Sci Inc, Seattle, WA USA. EM srinne@uw.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A2339 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839101511 ER PT J AU Ryden, AM Martin, JL Ng, CY Mitchell, M Santiago, S Zeidler, MR AF Ryden, A. M. Martin, J. L. Ng, C. Y. Mitchell, M. Santiago, S. Zeidler, M. R. TI Association Between The Development Of Incident Diagnosis Of Diabetes And Obstructive Sleep Apnea In Young Veterans: A Retrospective Cohort Study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Ryden, A. M.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Martin, J. L.; Mitchell, M.] UCLA, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, North Hills, CA USA. [Ng, C. Y.] Loma Linda Univ, Med Ctr, Loma Linda, CA USA. [Santiago, S.; Zeidler, M. R.] Univ Calif Los Angeles, WLA VA, Los Angeles, CA USA. EM armandryden@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A3476 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839103058 ER PT J AU Saketkoo, L Mittoo, S Huscher, D Dellaripa, P Denton, C Distler, O Fischer, A Flaherty, KR Frankel, S Khanna, D Kowal-Bielecka, O LeSage, D Merkel, P Oddis, C Phillips, K Pittrow, D Sarver, C Sandorfi, N Christmann, R Swigris, J Wells, A Antoniou, K Baughman, RP Castelino, F Christopher-Stine, L Danoff, S Highland, K Hummers, L Shah, A Kim, D Lynch, D Miller, F Proudman, S Richeldi, L Ryu, JH Seibold, J Strand, V Matteson, E Brown, KK AF Saketkoo, L. Mittoo, S. Huscher, D. Dellaripa, P. Denton, C. Distler, O. Fischer, A. Flaherty, K. R. Frankel, S. Khanna, D. Kowal-Bielecka, O. LeSage, D. Merkel, P. Oddis, C. Phillips, K. Pittrow, D. Sarver, C. Sandorfi, N. Christmann, R. Swigris, J. Wells, A. Antoniou, K. Baughman, R. P. Castelino, F. Christopher-Stine, L. Danoff, S. Highland, K. Hummers, L. Shah, A. Kim, D. Lynch, D. Miller, F. Proudman, S. Richeldi, L. Ryu, J. H. Seibold, J. Strand, V. Matteson, E. Brown, K. K. TI Provisional Consensus On Domains And Instruments In Connective Tissue Disease Related Interstitial Lung Disease And Idiopathic Pulmonary Fibrosis For Use In Clinical Trials SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. [Mittoo, S.] Univ Toronto, Toronto, ON, Canada. [Huscher, D.] German Rheumatism Res Ctr, Berlin, Germany. [Dellaripa, P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Denton, C.] Royal Free Hosp, London, England. [Distler, O.] Univ Zurich Hosp, Zurich, Switzerland. [Fischer, A.; Swigris, J.; Lynch, D.; Brown, K. K.] Natl Jewish Hlth, Denver, CO USA. [Flaherty, K. R.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Frankel, S.] Univ Manitoba, Winnipeg, MB R3T 2N2, Canada. [Khanna, D.; Phillips, K.] Univ Michigan, Ann Arbor, MI 48109 USA. [Kowal-Bielecka, O.] Med Univ Bialystok, Bialystok, Poland. [LeSage, D.] Rheumatoid Arthrit, New Orleans, LA USA. [Merkel, P.; Sandorfi, N.] Univ Penn, Philadelphia, PA 19104 USA. [Oddis, C.] Univ Pittsburgh, Pittsburgh, PA USA. [Pittrow, D.] Univ Dresden, Dresden, Germany. [Sarver, C.] Dermatomyositis ILD, Baltimore, MD USA. [Christmann, R.] Boston Univ, Boston, MA 02215 USA. [Wells, A.] Royal Brompton Hosp, London, England. [Wells, A.] Natl Heart & Lung Inst, London, England. [Antoniou, K.] Univ Crete, Iraklion, NE, Greece. [Baughman, R. P.] Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. [Castelino, F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Christopher-Stine, L.; Danoff, S.; Hummers, L.; Shah, A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Highland, K.] Med Univ South Carolina, Charleston, SC USA. [Kim, D.] Univ Ulsan, Seoul, South Korea. [Miller, F.] NIEHS, Bethesda, MD USA. [Proudman, S.] Royal Adelaide Hosp, Adelaide, SA, Australia. [Richeldi, L.] Univ Modena & Reggio Emilia, Modena, Italy. [Ryu, J. H.; Matteson, E.] Mayo Clin, Rochester, MN USA. [Seibold, J.] Scleroderma Res Consultants LLC, Avon, CT USA. [Strand, V.] Stanford Univ, Palo Alto, CA 94304 USA. EM ctd.ild@gmail.com NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A2352 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839101524 ER PT J AU Seumois, G Vijayanand, P Simpson, LJ Abdul-Wajid, S Baumjohann, D Panduro, M Huang, X Interlandi, J Djuretic, IM Brown, DR Sharpe, A Rao, A Ansel, KM AF Seumois, G. Vijayanand, P. Simpson, L. J. Abdul-Wajid, S. Baumjohann, D. Panduro, M. Huang, X. Interlandi, J. Djuretic, I. M. Brown, D. R. Sharpe, A. Rao, A. Ansel, K. M. TI Interleukin-4 Production By Follicular Helper T Cells Requires The Conserved Il4 Enhancer Hypersensitivity Site V SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Seumois, G.; Vijayanand, P.; Rao, A.] La Jolla Inst Allergy & Immunol, San Diego, CA USA. [Simpson, L. J.; Abdul-Wajid, S.; Baumjohann, D.; Panduro, M.; Huang, X.; Ansel, K. M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Interlandi, J.; Djuretic, I. M.; Sharpe, A.] Harvard Med Sch, Boston, MA USA. [Brown, D. R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sharpe, A.] Brigham & Womens Hospita, Boston, MA USA. EM gregory@liai.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A4151 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838400587 ER PT J AU Similowski, T Eriksson, G Postma, D Jenkins, CR Anzueto, A Make, BJ Fageras, M Persson, A Calverley, PM AF Similowski, T. Eriksson, G. Postma, D. Jenkins, C. R. Anzueto, A. Make, B. J. Fageras, M. Persson, A. Calverley, P. M. TI Early Efficacy Of Budesonide/formoterol In Patients With Moderate, Severe, And Very Severe COPD SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Similowski, T.] Grp Hosp Pitie Salpetriere, Serv Pneumol, Paris, France. [Eriksson, G.; Fageras, M.; Persson, A.] AstraZeneca R&D, Molndal, Sweden. [Postma, D.] Univ Med Ctr Groningen, Groningen, Netherlands. [Jenkins, C. R.] Univ Sydney, Camperdown, NSW, Australia. [Jenkins, C. R.] Woolcock Inst Med Res, Camperdown, NSW, Australia. [Anzueto, A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Anzueto, A.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Make, B. J.] Natl Jewish Hlth, Denver, CO USA. [Calverley, P. M.] Aintree Univ Hosp NHS Fdn Trust, Liverpool, Merseyside, England. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A4377 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838401020 ER PT J AU Slatore, CG Au, DH Curtis, JR Press, N Wiener, RS Ganzini, L AF Slatore, C. G. Au, D. H. Curtis, J. R. Press, N. Wiener, R. S. Ganzini, L. TI What The (heck) Is A Nodule? A Qualitative Study Of Veterans' Reactions To Finding An Incidental Pulmonary Nodule SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Slatore, C. G.; Ganzini, L.] Portland VA Med Ctr, Portland, OR USA. [Au, D. H.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Curtis, J. R.] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. [Press, N.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Wiener, R. S.] Boston Univ, Sch Med, Boston, MA 02118 USA. EM slatore@ohsu.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A2151 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839101323 ER PT J AU Smart, A Thompson, BT Clark, BJ Macht, M Benson, AB Burnham, EL Moss, M AF Smart, A. Thompson, B. T. Clark, B. J. Macht, M. Benson, A. B. Burnham, E. L. Moss, M. CA NIH NHLBI ARDS Network TI Surrogate Informed Consent For Genetic Substudies In Ards Network Trials SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Smart, A.; Clark, B. J.; Macht, M.; Benson, A. B.; Burnham, E. L.; Moss, M.] Univ Colorado Denver, Aurora, CO USA. [Thompson, B. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM alexandra.smart@ucdenver.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A4448 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838401091 ER PT J AU Sullivan, DR Duckart, JP Slatore, CG AF Sullivan, D. R. Duckart, J. P. Slatore, C. G. TI Chemotherapy Utilization In Advanced Non-Small Cell Lung Cancer Patients With Depression SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Sullivan, D. R.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Duckart, J. P.; Slatore, C. G.] Portland VA Med Ctr, Portland, OR USA. EM sullivad@ohsu.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A2153 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839101325 ER PT J AU Suter, MJ Kelly, VJ Chee, A Applegate, MB Tan, KM Hariri, LP Musch, G Harris, RS Winkler, T AF Suter, M. J. Kelly, V. J. Chee, A. Applegate, M. B. Tan, K. M. Hariri, L. P. Musch, G. Harris, R. S. Winkler, T. TI Real-Time Dynamic Assessment Of Airway Behavior Using Optical Frequency Domain Imaging SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Suter, M. J.; Kelly, V. J.; Chee, A.; Applegate, M. B.; Tan, K. M.; Hariri, L. P.; Musch, G.; Harris, R. S.; Winkler, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Suter, M. J.; Tan, K. M.; Hariri, L. P.; Harris, R. S.] Harvard Med Sch, Boston, MA USA. EM msuter@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A5449 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838402237 ER PT J AU Suter, MJ Hariri, LP Chee, A Tan, KM Bouma, BE Shishkov, M Tearney, GJ Channick, CL Lanuti, M Mark, EJ Mino-Kenudson, M AF Suter, M. J. Hariri, L. P. Chee, A. Tan, K. M. Bouma, B. E. Shishkov, M. Tearney, G. J. Channick, C. L. Lanuti, M. Mark, E. J. Mino-Kenudson, M. TI Transbronchial Optical Coherence Tomography To Increase The Diagnostic Yield Of Bronchial Biopsy SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Suter, M. J.; Hariri, L. P.; Chee, A.; Tan, K. M.; Bouma, B. E.; Shishkov, M.; Tearney, G. J.; Channick, C. L.; Lanuti, M.; Mark, E. J.; Mino-Kenudson, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Suter, M. J.; Hariri, L. P.; Chee, A.; Tan, K. M.; Bouma, B. E.; Shishkov, M.; Tearney, G. J.; Lanuti, M.; Mark, E. J.; Mino-Kenudson, M.] Harvard Med Sch, Boston, MA USA. EM msuter@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A3589 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838400042 ER PT J AU Tanner, NT Shamblin, C Idleman, L Egede, LE Gebregziabher, M Silvestri, GA AF Tanner, N. T. Shamblin, C. Idleman, L. Egede, L. E. Gebregziabher, M. Silvestri, G. A. TI Attitudes Toward Lung Cancer Screening Among Us Veteran Smokers And Their Non-Smoking Counterparts SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Tanner, N. T.; Shamblin, C.; Egede, L. E.; Gebregziabher, M.; Silvestri, G. A.] Med Univ South Carolina, Charleston, SC USA. [Idleman, L.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. EM tripici@musc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A3925 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838400362 ER PT J AU Tejera, P Gupta, K Owen, CA Christiani, DC AF Tejera, P. Gupta, K. Owen, C. A. Christiani, D. C. TI Pi3 (pre-Elafin); Functional Genomics And Acute Lung Injury Development SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Tejera, P.; Christiani, D. C.] Harvard Sch Publ Hlth, Boston, MA USA. [Gupta, K.; Owen, C. A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Owen, C. A.] Harvard Med Sch, Boston, MA USA. [Christiani, D. C.] Massachusetts Gen Hosp, Boston, MA USA. EM ptejera@hsph.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A1250 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839100232 ER PT J AU Van den Blink, B Burggraaf, J Morrison, LD Ginns, LC Wijsenbeek, MS Moerland, M Dillingh, MR Lupher, M AF Van den Blink, B. Burggraaf, J. Morrison, L. D. Ginns, L. C. Wijsenbeek, M. S. Moerland, M. Dillingh, M. R. Lupher, M. TI A Phase I Study Of Prm-151 In Patients With Idiopathic Pulmonary Fibrosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Van den Blink, B.; Wijsenbeek, M. S.] ErasmusMC, Rotterdam, Netherlands. [Burggraaf, J.; Moerland, M.; Dillingh, M. R.] Ctr Human Drug Res, Leiden, Netherlands. [Morrison, L. D.] Duke Univ, Med Ctr, Durham, NC USA. [Ginns, L. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ginns, L. C.] Harvard Med Sch, Boston, MA USA. [Lupher, M.] Promedior Inc, Lexington, MA USA. EM B.vandenBlink@erasmusmc.nl NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A5707 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838402475 ER PT J AU Van Koeverden, I Bowler, RP Blanc, PD Arjomandi, M AF Van Koeverden, I. Bowler, R. P. Blanc, P. D. Arjomandi, M. TI Role Of Occupational And Environmental Exposures To Secondhand Smoke In COPD Risk Among Smokers: A Subgroup Analysis Of COPDgene Study Cohort SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Van Koeverden, I.; Blanc, P. D.; Arjomandi, M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Bowler, R. P.] Natl Jewish Hlth & Res Ctr, Denver, CO USA. EM mehrdad.arjomandi@ucsf.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A3679 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838400132 ER PT J AU Venegas, JG Greenblatt, EE Kelly, VJ Winkler, T Kone, M Katz, I Martin, AR Montesantos, S Caillibotte, G Harris, RS AF Venegas, J. G. Greenblatt, E. E. Kelly, V. J. Winkler, T. Kone, M. Katz, I. Martin, A. R. Montesantos, S. Caillibotte, G. Harris, R. S. TI Effect Of Carrier Gas On The Relationship Between Regional Ventilation And Aerosol Deposition In Bronchoconstricted Subjects With Asthma SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Venegas, J. G.; Greenblatt, E. E.; Kelly, V. J.; Winkler, T.; Kone, M.; Harris, R. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Venegas, J. G.; Kelly, V. J.; Winkler, T.; Kone, M.; Harris, R. S.] Harvard Med Sch, Boston, MA USA. [Greenblatt, E. E.] MIT, Boston, MA USA. [Katz, I.; Martin, A. R.; Montesantos, S.; Caillibotte, G.] Air Liquide R&D, Jouy En Josas, France. EM eeg@mit.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A5444 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838402232 ER PT J AU Wellman, TJ De Prost, N Winkler, T Musch, G Tucci, M Chu, JH Baron, RM Raby, BA Melo, MFV AF Wellman, T. J. De Prost, N. Winkler, T. Musch, G. Tucci, M. Chu, J. -H. Baron, R. M. Raby, B. A. Melo, M. F. Vidal TI Non-Dependent Lung Regions Demonstrate Relative Upregulation Of Vili-Associated Genes And Late Increases In Fdg Uptake During 24 Hours Of Mechanical Ventilation And Endotoxin Infusion In Supine Sheep SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Wellman, T. J.] Boston Univ, Boston, MA 02215 USA. [De Prost, N.; Winkler, T.; Musch, G.; Tucci, M.; Melo, M. F. Vidal] Massachusetts Gen Hosp, Boston, MA 02114 USA. [De Prost, N.; Winkler, T.; Musch, G.; Tucci, M.; Melo, M. F. Vidal] Harvard Med Sch, Boston, MA USA. [Chu, J. -H.; Baron, R. M.; Raby, B. A.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA. EM twellman@bu.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A3501 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839103074 ER PT J AU Wongviriyawong, C Harris, RS Winkler, T Venegas, JG AF Wongviriyawong, C. Harris, R. S. Winkler, T. Venegas, J. G. TI Regional Heterogeneity In Peripheral Airway Reactivity, What Is Behind It? SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society CY MAY 17-22, 2013 CL Philadelphia, PA SP Amer Thorac Soc C1 [Wongviriyawong, C.] Chulabhorn Hosp, Bangkok, Thailand. [Harris, R. S.; Winkler, T.; Venegas, J. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Harris, R. S.; Winkler, T.; Venegas, J. G.] Harvard Med Sch, Boston, MA USA. EM chanikaw@mtec.or.th NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A1044 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839100027 ER PT J AU Yang, IV Pedersen, B Hennessy, C Davidson, E Guardela, BJ Tedrow, JR Correll, M Geraci, MW Quackenbush, J Sciurba, FC Spira, A Kaminski, N Schwartz, DA AF Yang, I. V. Pedersen, B. Hennessy, C. Davidson, E. Guardela, B. Juan Tedrow, J. R. Correll, M. Geraci, M. W. Quackenbush, J. Sciurba, F. C. Spira, A. Kaminski, N. Schwartz, D. A. TI Methyl-Eqtl Analysis In Idiopathic Pulmonary Fibrosis (ipf) SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Yang, I. V.; Pedersen, B.; Hennessy, C.; Davidson, E.; Geraci, M. W.; Schwartz, D. A.] Univ Colorado, Sch Med, Aurora, CO USA. [Guardela, B. Juan; Tedrow, J. R.; Sciurba, F. C.; Kaminski, N.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Correll, M.; Quackenbush, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Correll, M.; Quackenbush, J.] Havard Sch Publ Hlth, Boston, MA USA. [Spira, A.] Boston Univ, Sch Med, Boston, MA 02118 USA. EM ivana.yang@ucdenver.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A5756 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838402514 ER PT J AU Yonker, LM Scirica, C Taveras, E Kinane, T Tse, S AF Yonker, L. M. Scirica, C. Taveras, E. Kinane, T. Tse, S. TI Obesity-Related Asthma In High Versus Low Income Communities SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Yonker, L. M.; Scirica, C.; Kinane, T.; Tse, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Taveras, E.] Boston Childrens Hosp, Boston, MA USA. EM lyonker@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A5006 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838401640 ER PT J AU Yoon, SH Goldstein, R Jati, A Arndt, W AF Yoon, S. H. Goldstein, R. Jati, A. Arndt, W. TI Low Dose CT Lung Cancer Screening Experience At A Va Medical Center SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Yoon, S. H.; Goldstein, R.; Jati, A.; Arndt, W.] VA Boston HealthCare, Boston, MA USA. EM sue.yoon@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A4967 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838401610 ER PT J AU Yu, S Christiani, DC Gong, MN AF Yu, S. Christiani, D. C. Gong, M. N. TI Role Of Diabetes In The Development Of Acute Respiratory Distress Syndrome SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Yu, S.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Christiani, D. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gong, M. N.] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838401106 ER PT J AU Zaremba, S Brueckmann, B Malviya, S Grosse-Sundrup, M Malhotra, A Eikermann, M AF Zaremba, S. Brueckmann, B. Malviya, S. Grosse-Sundrup, M. Malhotra, A. Eikermann, M. TI Effects Of Cpap Treatment On Respiratory Function In The Recovery Room Following Weight Loss-Surgery: A Cross-Over Design, Randomized Controlled Trial SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Zaremba, S.; Brueckmann, B.; Malviya, S.; Grosse-Sundrup, M.; Eikermann, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Malhotra, A.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A5951 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838402710 ER PT J AU Zeidler, MR Martin, JL Omachi, TA Schneider, H Badr, MS AF Zeidler, M. R. Martin, J. L. Omachi, T. A. Schneider, H. Badr, M. S. TI Characterization Of Sleep In The Spiromics Cohort SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Zeidler, M. R.] Univ Calif Los Angeles, WLA VA, Los Angeles, CA USA. [Martin, J. L.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, North Hills, CA USA. [Omachi, T. A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Schneider, H.] Johns Hopkins Med Sch, Baltimore, MD USA. [Badr, M. S.] John Dingell VAMC, Detroit, MI USA. [Badr, M. S.] Wayne State Univ, Detroit, MI USA. EM MZeidler@mednet.ucla.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A2889 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TO UT WOS:000209839102278 ER PT J AU Zhai, R Zhao, Y Bajwa, E Thompson, BT Christiani, DC AF Zhai, R. Zhao, Y. Bajwa, E. Thompson, B. T. Christiani, D. C. TI Population Attributable Fractions For Acute Respiratory Distress Syndrome In Critically Ill Patients SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Zhai, R.; Zhao, Y.] Harvard Sch Publ Hlth, Boston, MA USA. [Bajwa, E.; Thompson, B. T.; Christiani, D. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2013 VL 187 MA A5289 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TH UT WOS:000209838402079 ER PT B AU Yuan, GC AF Yuan, Guo-Cheng GP Informat Resources Management Assoc TI Prediction of Epigenetic Target Sites by Using Genomic DNA Sequence SO BIOINFORMATICS: CONCEPTS, METHODOLOGIES, TOOLS, AND APPLICATIONS LA English DT Article; Book Chapter ID ENCODED NUCLEOSOME ORGANIZATION; CPG ISLAND METHYLATION; EMBRYONIC STEM-CELLS; HISTONE MODIFICATIONS; CHROMATIN-STRUCTURE; SACCHAROMYCES-CEREVISIAE; GENE-EXPRESSION; NONCODING RNAS; X-CHROMOSOME; YEAST GENOME AB Epigenetic regulation provides an extra layer of gene control in addition to the genomic sequence and is critical for the maintenance of cell-type specific gene expression programs. Significant changes of epigenetic patterns have been linked to developmental stages, environmental exposure, ageing, and diet. However, the regulatory mechanisms for epigenetic recruitment, maintenance, and switch are still poorly understood. Computational biology provides tools to deeply uncover hidden connections and these tools have played a major role in shaping the current understanding of gene regulation, but its application in epigenetics is still in the infancy. This chapter reviews some recent developments of computational approaches to predict epigenetic target sites. C1 [Yuan, Guo-Cheng] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Yuan, Guo-Cheng] Dana Farber Canc Inst, Boston, MA USA. RP Yuan, GC (reprint author), Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. NR 105 TC 0 Z9 0 U1 0 U2 0 PU IGI GLOBAL PI HERSEY PA 701 E CHOCOLATE AVE, STE 200, HERSEY, PA 17033-1240 USA BN 978-1-4666-3605-7; 978-1-4666-3604-0 PY 2013 BP 498 EP 512 DI 10.4018/978-1-4666-3604-0.ch028 D2 10.4018/978-1-4666-3604-0 PG 15 WC Computer Science, Information Systems; Mathematical & Computational Biology SC Computer Science; Mathematical & Computational Biology GA BD8EB UT WOS:000363871300031 ER PT S AU Monkul, ES Brambilla, P Nery, FG Hatch, JP Soares, JC AF Monkul, E. Serap Brambilla, Paolo Nery, Fabiano G. Hatch, John P. Soares, Jair C. BE Soares, JC Young, AH TI Brain Imaging Studies in Bipolar Disorder SO BIPOLAR DISORDERS: BASIC MECHANISMS AND THERAPEUTIC IMPLICATIONS, 2ND EDITION SE Medical Psychiatry LA English DT Article; Book Chapter ID MAGNETIC-RESONANCE-SPECTROSCOPY; POSITRON-EMISSION-TOMOGRAPHY; WHITE-MATTER HYPERINTENSITIES; SUBGENUAL PREFRONTAL CORTEX; MAJOR DEPRESSIVE DISORDER; N-ACETYL-ASPARTATE; SEROTONIN(1A) RECEPTOR-BINDING; NEUROLEPTIC-STABILIZER-NAIVE; CHOLINE-CONTAINING COMPOUNDS; ANTERIOR CINGULATE CORTEX C1 [Monkul, E. Serap; Nery, Fabiano G.; Hatch, John P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, Mood Disorders Clin Neurosci Program, San Antonio, TX 78229 USA. [Monkul, E. Serap] Dokuz Eylul Univ, Sch Med, Dept Psychiat, Izmir, Turkey. [Brambilla, Paolo] Univ Udine, Dept Pathol & Expt & Clin Med, Sect Psychiat, I-33100 Udine, Italy. [Brambilla, Paolo] Sci Inst IRCCS E Medea, Bosisio Parini, Italy. [Nery, Fabiano G.] South Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. [Nery, Fabiano G.] Univ Sao Paulo, Sch Med, Inst Psychiat, Sao Paulo, Brazil. [Hatch, John P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Orthodont, San Antonio, TX 78229 USA. [Soares, Jair C.] Univ N Carolina, Sch Med, Dept Psychiat, Ctr Excellence Res & Treatment Bipolar Disorders, Chapel Hill, NC USA. RP Monkul, ES (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, Mood Disorders Clin Neurosci Program, San Antonio, TX 78229 USA. NR 172 TC 0 Z9 0 U1 1 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL ST, LONDON, EC2A 4LQ, ENGLAND SN 2158-1770 BN 978-1-4200-2115-8; 978-0-8493-9897-1 J9 MED PSYCHIATRY PY 2013 BP 161 EP 187 PG 27 WC Psychiatry; Psychology SC Psychiatry; Psychology GA BD6OJ UT WOS:000362441200010 ER PT J AU Hayano, K Desai, GS Kambadakone, AR Fuentes, JM Tanabe, KK Sahani, DV AF Hayano, Koichi Desai, Gaurav S. Kambadakone, Avinash R. Fuentes, Jorge M. Tanabe, Kenneth K. Sahani, Dushyant V. TI Quantitative characterization of hepatocellular carcinoma and metastatic liver tumor by CT perfusion SO CANCER IMAGING LA English DT Article DE Computed tomography perfusion; hepatocellular carcinoma; angiogenesis; metastatic liver tumor ID COMPUTED-TOMOGRAPHY; CONTRAST ENHANCEMENT; ANGIOGENESIS; BIOMARKERS; PARAMETERS; MANAGEMENT; SEVERITY; DISEASE; TIME AB Purpose: To evaluate the diagnostic value of computed tomography perfusion (CTP) in the distinction of hepatocellular carcinomas (HCCs) from metastatic liver tumors. Materials and methods: CTP data from 90 liver tumors (HCC 38, metastasis 52) in 31 patients (16 men and 15 women; mean age 60.3 years) were studied. CTP was performed on a 16/64 multidetector-row CT scanner using a 30-s duration cine acquisition after rapid bolus injection (5-7 ml/s) of 50-70 ml of iodinated contrast medium. The CTP data were analyzed using a deconvolution model. Metastatic tumors were grouped into hypovascular (n=36) and hypervascular (n=16) tumors. Results and conclusion: The hypovascular metastases showed a significantly lower blood flow (BF) and blood volume (BV), and higher mean transit time (MTT) than HCC (all P<0.0001). BF, BV, and MTT of HCCs were substantially lower than those of hypervascular metastases (P=0.02, P< 0.0001, P=0.03, respectively). A receiver-operating characteristic analysis showed that BV was a useful marker to distinguish HCCs from hypervascular metastases. C1 [Hayano, Koichi; Desai, Gaurav S.; Kambadakone, Avinash R.; Fuentes, Jorge M.; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Tanabe, Kenneth K.] Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@partners.org OI Fuentes-Orrego, Jorge/0000-0002-9254-0746 NR 35 TC 5 Z9 5 U1 0 U2 2 PU E-MED PI LONDON PA PO BOX 29761, LONDON, NW3 7ZS, ENGLAND SN 1470-7330 EI 1740-5025 J9 CANCER IMAGING JI Cancer Imaging PY 2013 VL 13 IS 4 BP 512 EP 519 DI 10.1102/1470-7330.2013.0040 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA V41KC UT WOS:000209544100007 PM 24334461 ER PT J AU Cheng, JM Tirumani, SH Kim, KW Saboo, SS Baez, JC Shinagare, AB AF Cheng, Joan M. Tirumani, Sree Harsha Kim, Kyung Won Saboo, Sachin S. Baez, Juan C. Shinagare, Atul B. TI Malignant abdominal rocks: where do they come from? SO CANCER IMAGING LA English DT Review DE Malignancy; calcifications; computed tomography; abdomen ID GASTROINTESTINAL STROMAL TUMORS; RADIOLOGIC-PATHOLOGICAL CORRELATION; SOFT-TISSUE SARCOMAS; GERM-CELL TUMORS; COMPUTED-TOMOGRAPHY; COLORECTAL-CARCINOMA; METASTATIC PATTERNS; CT FEATURES; CALCIFICATION; CHONDROSARCOMA AB For the radiologist, calcifications in an abdominal malignancy raise questions of both diagnostic and prognostic significance. Although certain cancers are well known to calcify, such as colorectal and ovarian, malignant abdominal calcifications actually arise from a wide variety of epithelial, mesenchymal, lymphoid, or germ cell neoplasms. The pathophysiology of calcification in abdominal malignancies is heterogeneous and incompletely understood. Calcifications may present primarily, in untreated tumors, or develop during treatment; the latter can occur in variable clinical settings. A basic understanding of the varied pathogenic etiology can assist the radiologist in assessing disease status. By presenting an assortment of calcified abdominal malignancies on computed tomography in varied clinical settings, we aim not only to inform the differential diagnosis, but also to clarify the prognosis of calcifications in abdominal malignancies. C1 [Cheng, Joan M.; Tirumani, Sree Harsha; Kim, Kyung Won] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Cheng, Joan M.; Tirumani, Sree Harsha; Kim, Kyung Won; Saboo, Sachin S.; Baez, Juan C.; Shinagare, Atul B.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Tirumani, SH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM stirumani@partners.org NR 51 TC 1 Z9 1 U1 0 U2 0 PU E-MED PI LONDON PA PO BOX 29761, LONDON, NW3 7ZS, ENGLAND SN 1470-7330 EI 1740-5025 J9 CANCER IMAGING JI Cancer Imaging PY 2013 VL 13 IS 4 BP 527 EP 539 DI 10.1102/1470-7330.2013.0048 PG 13 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA V41KC UT WOS:000209544100009 PM 24334568 ER PT J AU Ganten, MK Schuessler, M Bauerle, T Muenter, M Schlemmer, HP Jensen, A Brand, K Dueck, M Dinkel, J Kopp-Schneider, A Fritzsche, K Stieltjes, B AF Ganten, Maria-Katharina Schuessler, Maximilian Baeuerle, Tobias Muenter, Marc Schlemmer, Heinz-Peter Jensen, Alexandra Brand, Karsten Dueck, Margret Dinkel, Julien Kopp-Schneider, Annette Fritzsche, Klaus Stieltjes, Bram TI The role of perfusion effects in monitoring of chemoradiotherapy of rectal carcinoma using diffusion-weighted imaging SO CANCER IMAGING LA English DT Article DE Intraroxel incoherent motion model; rectal carcinoma; tumor response; diffusion-weighted imaging; chemoradiotherapy; monitoring ID RADIATION-THERAPY; PREOPERATIVE CHEMORADIATION; TUMOR MICROCIRCULATION; EARLY RESPONSE; CANCER; MR; CHEMOTHERAPY; RADIOTHERAPY; COEFFICIENT; PREDICTION AB Purpose: The aim of this study was to characterize and understand the therapy-induced changes in diffusion parameters in rectal carcinoma under chemoradiotherapy (CRT). The current literature shows conflicting results in this regard. We applied the intravoxel incoherent motion model, which allows for the differentiation between diffusion (D) and perfusion (f) effects, to further elucidate potential underlying causes for these divergent reports. Materials and methods: Eighteen patients with primary rectal carcinoma undergoing preoperative CRT were examined before, during, and after neoadjuvant CRT using diffusion-weighted imaging. Using the intravoxel incoherent motion approach, f and D were extracted and compared with postoperative tumor downstaging and volume. Results: Initial diffusion-derived parameters were within a narrow range (D-1 = 0.94 +/- 0.12 x 10(-3) mm(2)/s). At follow-up, D rose significantly (D-2=1.18 +/- 0.13 x 10(-3) mm(2)/s; P<0.0001) and continued to increase significantly after CRT (D-3=1.24 +/- 0.14 x 10(-3) mm(2)/s; P<0.0001). The perfusion fraction f did not change significantly (f(1)=9.4 +/- 2.0%, f(2)= 9.4 +/- 1.7%, f(3)=9.5 +/- 2.7%). Mean volume (V) decreased significantly (V-1=16,992 +/- 13,083 mm(3); V-2=12,793 +/- 8317 mm(3), V-3=9718 +/- 6154 mm(3)). T-downstaging (10:18 patients) showed no significant correlation with diffusion-derived parameters. Conclusions: Conflicting results in the literature considering apparent diffusion coefficient (ADC) changes in rectal carcinoma under CRT for patients showing T-downstaging are unlikely to be due to perfusion effects. Our data support the view that under effective therapy, an increase in D/ADC can be observed. C1 [Ganten, Maria-Katharina; Schuessler, Maximilian; Schlemmer, Heinz-Peter; Dinkel, Julien] German Canc Res Ctr, Dept Radiol E010, D-69120 Heidelberg, Germany. [Baeuerle, Tobias] German Canc Res Ctr, Dept Med Phys Radiol E020, D-69120 Heidelberg, Germany. [Muenter, Marc; Jensen, Alexandra] Heidelberg Univ, Dept Radiat Therapy, Heidelberg, Germany. [Brand, Karsten] Heidelberg Univ, Dept Pathol, Heidelberg, Germany. [Dueck, Margret] Heidelberg Univ, Dept Surg, Heidelberg, Germany. [Dinkel, Julien] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Kopp-Schneider, Annette] German Canc Res Ctr, Med Biostat, Dept Biostat C060, D-69120 Heidelberg, Germany. [Fritzsche, Klaus] German Canc Res Ctr, Med & Biol Informat E130, D-69120 Heidelberg, Germany. [Fritzsche, Klaus; Stieltjes, Bram] German Canc Res Ctr, Quantitat Imaging Based Dis Characterizat E011, D-69120 Heidelberg, Germany. RP Ganten, MK (reprint author), German Canc Res Ctr, Dept Radiol E010, INF 280, D-69120 Heidelberg, Germany. EM m.ganten@dkfz.de RI Maier-Hein, Klaus/M-6250-2016; OI Maier-Hein, Klaus/0000-0002-6626-2463; Kopp-Schneider, Annette/0000-0002-1810-0267 FU DFG (Deutsche Forschungsgesellschaft) [GA 765/2-1] FX The authors thank the DFG (Deutsche Forschungsgesellschaft) for their support (GA 765/2-1). NR 39 TC 9 Z9 10 U1 0 U2 3 PU E-MED PI LONDON PA PO BOX 29761, LONDON, NW3 7ZS, ENGLAND SN 1470-7330 EI 1740-5025 J9 CANCER IMAGING JI Cancer Imaging PY 2013 VL 13 IS 4 BP 548 EP 556 DI 10.1102/1470-7330.2013.0045 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA V41KC UT WOS:000209544100011 PM 24334520 ER PT J AU O'Regan, K Breen, M Ramaiya, N Jagannathan, J DiPiro, PJ Hodi, FS Van den Abbeele, AD AF O'Regan, Kevin Breen, Micheal Ramaiya, Nikhil Jagannathan, Jyothi DiPiro, Pamela J. Hodi, F. Stephen Van den Abbeele, Annick D. TI Metastatic mucosal melanoma: imaging patterns of metastasis and recurrence SO CANCER IMAGING LA English DT Article DE Melanoma; mucous membrane; diagnostic imaging; tumor metastasis; integrated PET/CT ID MALIGNANT-MELANOMA; CUTANEOUS MELANOMA; SINONASAL MELANOMA; UVEAL MELANOMA; MUTATIONS; PATHWAYS; TRACT; BRAF AB Purpose: Mucosal melanoma is a rare but aggressive subtype of melanoma with unique clinicopathologic features. We hypothesize that mucosal melanoma shows predilection for separate and unique metastatic pathways. Materials and methods: This was a retrospective analysis of 19 patients (5 men and 14 women; median age 60 years, range 38-76 years) with metastatic mucosal melanoma presenting to a tertiary oncology center between 2005 and 2010. We performed a review of medical records and histologic and imaging studies to evaluate the natural history, metastatic patterns and the role of imaging in the management of patients with advanced mucosal melanoma. Results: At presentation, disease was confined to the primary site (58%, n=11) or to the regional lymph nodes (32%, n=6) in most patients. The most common site of metastasis was the lungs (89%, n=16), followed by the liver (67%, n =12) and peritoneum (44%, n=8). Sinonasal melanoma preferentially spread to the liver (100%, n=4), vaginal melanoma to the lungs (100%, n=7) and anal melanoma to the inguinal lymph nodes (100%, n=4). Conclusion: Pathways of metastatic spread in mucosal melanoma may differ from other forms of melanoma and between different primary sites of mucosal origin. C1 [O'Regan, Kevin; Breen, Micheal] Cork Univ Hosp, Dept Radiol, Cork, Ireland. [Ramaiya, Nikhil; Jagannathan, Jyothi; DiPiro, Pamela J.; Van den Abbeele, Annick D.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Hodi, F. Stephen] Dana Farber Canc Inst, Dept Cutaneous Oncol Program, Boston, MA 02115 USA. RP Breen, M (reprint author), Cork Univ Hosp, Dept Radiol, MBBChBAO, Cork, Ireland. EM m.breen@gmail.com OI Breen, Micheal/0000-0002-9141-8175 NR 24 TC 4 Z9 4 U1 1 U2 1 PU E-MED PI LONDON PA PO BOX 29761, LONDON, NW3 7ZS, ENGLAND SN 1470-7330 EI 1740-5025 J9 CANCER IMAGING JI Cancer Imaging PY 2013 VL 13 IS 4 BP 626 EP 632 DI 10.1102/1470-7330.2013.0055 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA V41KC UT WOS:000209544100018 PM 24434078 ER PT J AU Huang, YH Yuan, JP Righi, E Duda, DG Fukumura, D Poznansky, MC Jain, RK AF Huang, Yuhui Yuan, Jianping Righi, Elda Duda, Dan G. Fukumura, Dai Poznansky, Mark C. Jain, Rakesh K. TI Reconditioning the tumor immune microenvironment for a breast cancer vaccine therapy. SO CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2013 VL 73 SU 1 MA A67 DI 10.1158/1538-7445.TUMIMM2012-A67 PG 2 WC Oncology SC Oncology GA V40RS UT WOS:000209496300040 ER PT J AU Acha, MR Mills, R Chen, JX Wu, SM Milan, D AF Acha, M. Rav Mills, R. Chen, J. X. Wu, S. M. Milan, D. TI EXCITABILITY OF DIRECT REPROGRAMMED MURINE TAIL FIBROBLASTS: BETWEEN WILD-TYPE FIBROBLASTS AND CARDIOMYOCYTES SO CARDIOLOGY LA English DT Meeting Abstract C1 [Acha, M. Rav; Mills, R.; Milan, D.] Massachusetts Gen Hosp, Charlestown, MA USA. [Chen, J. X.; Wu, S. M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2013 VL 125 SU 2 MA 112 BP 126 EP 126 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V41LT UT WOS:000209548400112 ER PT J AU Rana, S Powe, CE Salahuddin, S Verlohren, S Perschel, FH Levine, RJ Lim, KH Wenger, JB Thadhani, R Karumanchi, SA AF Rana, S. Powe, C. E. Salahuddin, S. Verlohren, S. Perschel, F. H. Levine, R. J. Lim, K. H. Wenger, J. B. Thadhani, R. Karumanchi, S. A. TI ANGIOGENIC FACTORS AND THE RISK OF ADVERSE OUTCOMES IN WOMEN WITH SUSPECTED PREECLAMPSIA SO CARDIOLOGY LA English DT Meeting Abstract C1 [Rana, S.; Salahuddin, S.; Lim, K. H.; Karumanchi, S. A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Powe, C. E.; Wenger, J. B.; Thadhani, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Powe, C. E.; Wenger, J. B.; Thadhani, R.] Harvard Univ, Sch Med, Boston, MA USA. [Verlohren, S.; Perschel, F. H.] Charite, D-13353 Berlin, Germany. [Levine, R. J.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2013 VL 125 SU 2 MA 397 BP 411 EP 411 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V41LT UT WOS:000209548400395 ER PT J AU Gloy, VL Briel, M Bhatt, D Kashyap, S Schauer, P Mingrone, G Bucher, HC Nordmann, AJ AF Gloy, V. L. Briel, M. Bhatt, D. Kashyap, S. Schauer, P. Mingrone, G. Bucher, H. C. Nordmann, A. J. TI BARIATRIC SURGERY VERSUS NON-SURGICAL TREATMENT FOR OBESITY: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS SO CARDIOLOGY LA English DT Meeting Abstract C1 [Gloy, V. L.; Briel, M.; Bucher, H. C.; Nordmann, A. J.] Univ Basel Hosp, Basel Inst Clin Epidemiol & Biostat, CH-4031 Basel, Switzerland. [Briel, M.] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. [Bhatt, D.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, D.] Harvard Univ, Sch Med, Boston, MA USA. [Kashyap, S.] Cleveland Clin, Inst Endocrinol, Cleveland, OH 44106 USA. [Schauer, P.] Cleveland Clin, Bariatr & Metab Inst, Cleveland, OH 44106 USA. [Mingrone, G.] Univ Cattolica Sacro Cuore, Dept Internal Med, Rome, Italy. NR 0 TC 0 Z9 0 U1 2 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2013 VL 125 SU 2 MA 447 BP 461 EP 461 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V41LT UT WOS:000209548400445 ER PT S AU Merzenich, MM Nahum, M Van Vleet, TM AF Merzenich, Michael M. Nahum, Mor Van Vleet, Thomas M. BE Merzenich, MM Nahum, M VanVleet, TM TI Progress in Brain Research Introduction SO CHANGING BRAINS APPLYING BRAIN PLASTICITY TO ADVANCE AND RECOVER HUMAN ABILITY SE Progress in Brain Research LA English DT Editorial Material; Book Chapter ID AUDITORY-CORTEX; PLASTICITY; SEARCH; MEMORY C1 [Merzenich, Michael M.; Nahum, Mor; Van Vleet, Thomas M.] Posit Sci Corp, Brain Plast Inst, San Francisco, CA 94104 USA. [Nahum, Mor] Univ Calif Berkeley, Dept Optometry, Berkeley, CA 94720 USA. [Van Vleet, Thomas M.] US Dept Vet Affairs, Dept Vet Affairs, Martinez, CA USA. RP Merzenich, MM (reprint author), Posit Sci Corp, Brain Plast Inst, San Francisco, CA 94104 USA. NR 22 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-63327-9 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2013 VL 207 BP XXI EP XXVI PG 6 WC Neurosciences SC Neurosciences & Neurology GA BC0PS UT WOS:000349322100001 PM 24309266 ER PT B AU Gurkar, A Chu, KK Lee, SW AF Gurkar, Aditi Chu, Kiki Lee, Sam W. BE Madhusudan, S Wilson, DM TI p53 in DNA Damage, Repair and Cancer Therapeutics SO DNA REPAIR AND CANCER: FROM BENCH TO CLINIC LA English DT Article; Book Chapter ID WILD-TYPE P53; TUMOR-SUPPRESSOR P53; CELL-CYCLE ARREST; MANGANESE SUPEROXIDE-DISMUTASE; E1B 55-KILODALTON ONCOPROTEIN; INTERACTING PROTEIN KINASE-2; HUMAN-PAPILLOMAVIRUS TYPE-16; MOLECULAR-WEIGHT COMPOUND; UBIQUITIN LIGASE ACTIVITY; MDM2 ANTAGONIST NUTLIN-3 C1 [Lee, Sam W.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Lee, SW (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM agurkar@partners.org; kchu1@partners.org; swlee@partners.org NR 392 TC 2 Z9 2 U1 0 U2 1 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4665-7744-2; 978-1-4665-7743-5 PY 2013 BP 372 EP 425 D2 10.1201/b14587 PG 54 WC Oncology SC Oncology GA BC5UA UT WOS:000353575000014 ER PT J AU Cook, J Harb, G Ross, R AF Cook, J. Harb, G. Ross, R. TI Imagery rehearsal for post-traumatic nightmares: observations from two clinical trials SO EUROPEAN JOURNAL OF PSYCHOTRAUMATOLOGY LA English DT Meeting Abstract C1 [Cook, J.] Yale Sch Med, Dept Psychiat, New Haven, CT USA. [Cook, J.] Natl Ctr PTSD, West Haven, CT USA. [Harb, G.; Ross, R.] Univ Penn, Philadelphia, PA 19104 USA. [Harb, G.; Ross, R.] Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2000-8066 J9 EUR J PSYCHOTRAUMATO JI Eur. J. Psychotraumatol. PY 2013 VL 4 SU 1 PG 1 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA V44PH UT WOS:000209760400076 ER PT J AU Goutaudier, N Bui, E Sejourne, N Chabrol, H AF Goutaudier, N. Bui, E. Sejourne, N. Chabrol, H. TI Posttraumatic stress disorder symptoms in the first weeks following the preterm infant's hospital discharge SO EUROPEAN JOURNAL OF PSYCHOTRAUMATOLOGY LA English DT Meeting Abstract C1 [Goutaudier, N.; Sejourne, N.; Chabrol, H.] Univ Toulouse II Mirail, Octogone Ctr Etud & Reche Psychopathol, Toulouse, France. [Bui, E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Bui, E.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2000-8066 J9 EUR J PSYCHOTRAUMATO JI Eur. J. Psychotraumatol. PY 2013 VL 4 SU 1 PG 1 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA V44PH UT WOS:000209760400455 ER PT J AU Ruggiero, K Price, M McCauley, J Gros, K Resnick, H AF Ruggiero, K. Price, M. McCauley, J. Gros, K. Resnick, H. TI Bounce back now: a web-based intervention for youth and families affected by disaster SO EUROPEAN JOURNAL OF PSYCHOTRAUMATOLOGY LA English DT Meeting Abstract C1 [Ruggiero, K.; Price, M.; McCauley, J.; Resnick, H.] Med Univ South Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA. [Gros, K.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2000-8066 J9 EUR J PSYCHOTRAUMATO JI Eur. J. Psychotraumatol. PY 2013 VL 4 SU 1 PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA V44PH UT WOS:000209760400092 ER PT J AU Allakhyerdi, Z Comeau, MR Arment, M Agrawal, R Woodfolk, JA Sehmi, R Howie, KJ Gauvreau, GM Delespesse, G AF Allakhverdi, Zoulfia Comeau, Michael R. Arment, Myriam Agrawal, Rachana Woodfolk, Judith A. Sehmi, Roma Howie, Karen J. Gauvreau, Gail M. Delespesse, Guy TI Mast cell-activated bone marrow mesenchymal stromal cells regulate proliferation and lineage commitment of CD34(+) progenitor cells SO FRONTIERS IN IMMUNOLOGY LA English DT Article DE mast cells; bone marrow mesenchymal stromal cells; TSLP; circulating CD34+progenitor cells; asthma; allergic inflammation; Th2 response AB Background: Shortly after allergen exposure, the number of bone marrow (BM) and circulating CD34(+) progenitors increases. We aim to analyze the possible mechanism whereby the allergic reaction stimulates BM to release these effector cells in increased numbers. We hypothesize that mast cells (MCs) may play a predominant role in this process. Objective: To examine the effect of IgE-activated MCs on BM mesenchymal stromal cells which regulate proliferation and differentiation of CD34(+) progenitors. Methods: Primary MCs were derived from CD34(+) precursors and activated with IgE/anti-IgE. BM mesenchymal stromal cells were co-cultured with CD34(+) progenitor cells and stimulated with ILI/INF or IgE/anti-IgE-activated MCs in Transwell system. Results: BM mesenchymal stromal cells produce low level of thymic stromal lymphopoietin (TSLP) under steady state conditions, which is markedly increased by stimulation with proinflammatory cytokines 1151 and TNF or IgE-activated MCs. The latter also triggers bone marrow-derived mesenchymal stromal cells production of G-CSF, and GM-CSF while inhibiting SDF-1. MC-activated mesenchymal stromal cells stimulate CD34(+) cells to proliferate and to regulate their expression of early allergy-associated genes. Conclusion and Clinical Relevance: This in vitro study indicates that IgE-activated MCs trigger BM mesenchymal stromal cells to release TSLP and hematopoietic growth factors and to regulate the proliferation and lineage commitment of CD34(+) precursor cells. The data predict that the effective inhibition of MCs should impair mobilization and accumulation of allergic effector cells and thereby reduce the severity of allergic diseases. C1 [Allakhverdi, Zoulfia; Delespesse, Guy] CRCHUM Notre Dame Hosp, Lab Allergy, Montreal, PQ H2L 4M1, Canada. [Comeau, Michael R.] Amgen Inc, Inflammat Res, Seattle, WA USA. [Arment, Myriam] Immune Dis Inst, Ctr Human Cell Therapy, Boston, MA USA. [Agrawal, Rachana; Woodfolk, Judith A.] Univ Virginia, Dept Med, Div Allergy, Charlottesville, VA USA. [Sehmi, Roma] McMaster Univ, Firestone Inst Resp Hlth, Hamilton, ON, Canada. [Howie, Karen J.; Gauvreau, Gail M.] McMaster Univ, Asthma Res Grp, Hamilton, ON, Canada. RP Allakhyerdi, Z (reprint author), CRCHUM Notre Dame Hosp, Lab Allergy, 1560 Sherbrooke East St,M4211-K, Montreal, PQ H2L 4M1, Canada. EM zoulfia.allakhverdieva@mail.mcgill.ca; guy.jt.delespesse@umontreal.ca FU Allergen; Parker B. Francis fellowship FX We gratefully acknowledge the group of nurses and obstetricians at St-Luc Hospital (Montreal, QC, Canada) for providing us with umbilical cord blood. This work was supported by a grant from Allergen. Zoulfia Allakhverdi was a recipient of Parker B. Francis fellowship. NR 39 TC 6 Z9 6 U1 0 U2 2 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PY 2013 VL 4 AR UNSP 461 DI 10.3389/fimmu.2013.00461 PG 7 WC Immunology SC Immunology GA V38WS UT WOS:000209374100449 PM 24381572 ER PT J AU Choi, YI Duke-Cohan, JS Tan, J Gui, JG Singh, MK Epstein, JA Reinherz, EL AF Choi, Young I. Duke-Cohan, Jonathan S. Tan, Jing Gui, Jingang Singh, Manvendra K. Epstein, Jonathan A. Reinherz, Ellis L. TI Plxnd1 expression in thymocytes regulates their intrathymic migration while that in thymic endothelium impacts medullary topology SO FRONTIERS IN IMMUNOLOGY LA English DT Article DE plexind1; thymic development; thymic epithelial cells; angiogenesis; autoimmunity AB An important role for plexinD1 in thymic development is inferred from studies of germline Plxnd1 knockout (KO) mice where mislocalized CD69(+) thymocytes as well as ectopic thymic subcapsular medullary structures were observed. Given embryonic lethality of the Plxnd1(-/-) genotype, fetal liver transplantation was employed in these prior analyses. Such embryonic hematopoietic reconstitution may have transferred Plxnd1 KO endothelial and/or epithelial stem cells in addition to Plxnd1 KO lymphoid progenitors, thereby contributing to that phenotype. Here we use Plxnd1(flox/flox) mice crossed to pLck-Cre, pKeratin14-Cre, or pTek-Cre transgenic animals to create cell-type specific conditional knockout (CK0) lines involving thymocytes (D1ThyCKO), thymic epithelium (D1EpCKO), and thymic endothelium (D1EnCKO), respectively. These CKOs allowed us to directly assess the role of plexinD1 in each lineage. Loss of plexinD1 expression on double positive (DP) thymocytes leads to their aberrant migration and cortical retention after TCR-mediated positive selection. In contrast, ectopic medulla formation is a consequence of loss of plexinD1 expression on endothelial cells, in turn linked to dysregulation of thymic angiogenesis. D1 EpCKO thymi manifest neither abnormality. Collectively, our findings underscore the non-redundant roles for plexinD1 on thymocytes and endothelium, including the dynamic nature of medulla formation resulting from crosstalk between these thymic cellular components. C1 [Choi, Young I.; Duke-Cohan, Jonathan S.; Tan, Jing; Gui, Jingang; Reinherz, Ellis L.] Dana Farber Canc Inst, Immunobiol Lab, Dept Med Oncol, Boston, MA 02115 USA. [Choi, Young I.; Duke-Cohan, Jonathan S.; Gui, Jingang; Reinherz, Ellis L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Tan, Jing] North Sichuan Med Coll, Affiliated Hosp, Dept Hematol, Nanchong, Sichuan, Peoples R China. [Singh, Manvendra K.; Epstein, Jonathan A.] Univ Penn, Dept Cell & Dev Biol, Cardiovasc Inst, Philadelphia, PA 19104 USA. RP Reinherz, EL (reprint author), Dana Farber Canc Inst, Immunobiol Lab, Dept Med Oncol, 77 Ave Louis Pasteur,HIM 418, Boston, MA 02115 USA. EM ellis_reinherz@dfci.harvard.edu OI Singh, Manvendra/0000-0002-2884-0074; Duke-Cohan, Jonathan/0000-0002-9478-9609 FU National Institutes of Health [AI092378, AI019807, HL118768] FX We acknowledge the excellent technical assistance of Elizabeth Witten. This work was supported, in part, by National Institutes of Health Grants AI092378 to Young I. Choi and AI019807 to Ellis L. Reinherz and HL118768 to Jonathan A. Epstein. NR 57 TC 5 Z9 5 U1 0 U2 0 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PY 2013 VL 4 AR UNSP 392 DI 10.3389/fimmu.2013.00392 PG 13 WC Immunology SC Immunology GA V38WS UT WOS:000209374100381 PM 24312099 ER PT J AU Faustman, DL Davis, M AF Faustman, Denise L. Davis, Miriam TI TNF receptor 2 and disease: autoimmunity and regenerative medicine SO FRONTIERS IN IMMUNOLOGY LA English DT Review DE TNF; TNF receptor 2; autoimmune disease; type 1 diabetes; regeneration AB The regulatory cytokine tumor necrosis factor (TNF) exerts its effects through two receptors: TNFR1 and TNFR2. Defects in TNFR2 signaling are evident in a variety of autoimmune diseases. One new treatment strategy for autoimmune disease is selective destruction of autoreactive T cells by administration of TNF, TNF inducers, or TNFR2 agonism. A related strategy is to rely on TNFR2 agonism to induce T-regulatory cells (T-regs) that suppress cytotoxic T cells. Targeting TNFR2 as a treatment strategy is likely superior to TNFR1 because of its more limited cellular distribution on T cells, subsets of neurons, and a few other cell types, whereas TNFR1 is expressed throughout the body. This review focuses on TNFR2 expression, structure, and signaling; TNFR2 signaling in autoimmune disease; treatment strategies targeting TNFR2 in autoimmunity; and the potential for TNFR2 to facilitate end organ regeneration. C1 [Faustman, Denise L.; Davis, Miriam] Massachusetts Gen Hosp, Immunobiol Lab, Boston, MA 02129 USA. [Faustman, Denise L.] Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Faustman, DL (reprint author), Massachusetts Gen Hosp, Immunobiol Lab, Bldg 149,13th St,Room 3601, Boston, MA 02129 USA. EM faustman@helix.mgh.harvard.edu NR 107 TC 24 Z9 25 U1 1 U2 5 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PY 2013 VL 4 AR UNSP 478 DI 10.3389/fimmu.2013.00478 PG 8 WC Immunology SC Immunology GA V38WS UT WOS:000209374100466 PM 24391650 ER PT J AU Fiorentino, M Lammers, KM Levine, MM Sztein, MB Fasano, A AF Fiorentino, Maria Lammers, Karen M. Levine, Myron M. Sztein, Marcelo B. Fasano, Alessio TI In vitro intestinal mucosal epithelial responses to wild-type Salmonella Typhi and attenuated typhoid vaccines SO FRONTIERS IN IMMUNOLOGY LA English DT Article DE intestinal mucosal barrier; epithelial permeability; mucosal immunity; Salmonella Typhi; typhoid vaccines; cytokines AB Typhoid fever, caused by S. Typhi, is responsible for approximately 200,000 deaths per year worldwide. Little information is available regarding epithelium-bacterial interactions in S. Typhi infection. We have evaluated in vitro the effects of wild-type S. Typhi, the licensed Ty2la typhoid vaccine and the leading strains CVD 908-htrA and CVD 909 vaccine candidates on intestinal barrier function and immune response. Caco2 monolayers infected with wild-type S. Typhi exhibited alterations in the organization of tight junctions, increased paracellular permeability, and a rapid decrease in Trans-Epithelial Electrical Resistance as early as 4h post-exposure. S. Typhi triggered the secretion of interleukin (IL)-8 and 1156. Caco2 cells infected with the attenuated strains exhibited a milder pro-inflammatory response with minimal disruption of the barrier integrity. We conclude that wild-type S. Typhi causes marked transient alterations of the intestinal mucosa that are more pronounced than those observed with Ty2la or new generation attenuated typhoid vaccine candidates. C1 [Fiorentino, Maria; Lammers, Karen M.; Fasano, Alessio] Univ Maryland, Sch Med, Dept Pediat, Mucosal Biol Res Ctr, Baltimore, MD 21201 USA. [Levine, Myron M.; Sztein, Marcelo B.] Univ Maryland, Sch Med, Dept Pediat, Ctr Vaccine Dev, Baltimore, MD 21201 USA. RP Fasano, A (reprint author), Massachusetts Gen Hosp East, Mucosal Immunol & Biol Res Ctr, Bldg 114,16th St,Mail Stop 114-3503, Charlestown, MA 02129 USA. EM afasano@partners.org OI Fiorentino, Maria R/0000-0001-5318-7313 FU NIAID; NIH; DHHS [R01-AI036525, U19 AI082655] FX These studies were funded by NIAID, NIH, DHHS grants R01-AI036525 and U19 AI082655 (Cooperative Center for Translational Research in Human Immunology and Biodefense; CCHI) to Marcelo B. Sztein and Alessio Fasano. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. NR 63 TC 4 Z9 4 U1 0 U2 1 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PY 2013 VL 4 AR UNSP 17 DI 10.3389/fimmu.2013.00017 PG 15 WC Immunology SC Immunology GA V38WS UT WOS:000209374100017 PM 23408152 ER PT J AU Hong, HS Rajakumar, PA Billingsley, JM Reeves, RK Johnson, RP AF Hong, Henoch S. Rajakumar, Premeela A. Billingsley, James M. Reeves, R. Keith Johnson, R. Paul TI No monkey business: why studying NK cells in non-human primates pays off SO FRONTIERS IN IMMUNOLOGY LA English DT Review DE non-human primate models; rhesus macaques; NK cell subpopulations; transcriptional profiling AB Human NK (hNK) cells play a key role in mediating host immune responses against various infectious diseases. For practical reasons, the majority of the data on hNK cells has been generated using peripheral blood lymphocytes. In contrast, our knowledge of NK cells in human tissues is limited, and not much is known about developmental pathways of hNK cell subpopulations in vivo. Although research in mice has elucidated a number of fundamental features of NK cell biology, mouse, and hNK cells significantly differ in their subpopulations, functions, and receptor repertoires. Thus, there is a need for a model that is more closely related to humans and yet allows experimental manipulations. Non human primate models offer numerous opportunities for the study of NK cells, including the study of the role of NK cells after solid organ and stem cell transplantation, as well as in acute viral infection. Macaque NK cells can be depleted in vivo or adoptively transferred in an autologous system. All of these studies are either difficult or unethical to carry out in humans. Here we highlight recent advances in rhesus NK cell research and their parallels in humans. Using high-throughput transcriptional profiling, we demonstrate that the human cD56(bright) and CD56(dim) NK cell subsets have phenotypically and functionally analogous counterparts in rhesus macaques. Thus, the use of non human primate models offers the potential to substantially advance hNK cell research. C1 [Hong, Henoch S.; Rajakumar, Premeela A.; Billingsley, James M.; Reeves, R. Keith; Johnson, R. Paul] Harvard Univ, Sch Med, Div Immunol, New England Primate Res Ctr, Southborough, MA 01772 USA. [Johnson, R. Paul] Massachusetts Gen Hosp, Infect Dis Unit, Ragon Inst Massachusetts Gen Hosp MIT & Harvard, Boston, MA 02114 USA. RP Johnson, RP (reprint author), Harvard Univ, Sch Med, Div Immunol, New England Primate Res Ctr, One Pine Hill Dr, Southborough, MA 01772 USA. EM paul_johnson@hms.harvard.edu FU NIH (NEPRC) [P51 OD011103, R01 AI090735]; German Research Foundation [HO 4527/1-1] FX We thank Michelle Connole for her dedicated assistance with flow cytometric cell sorting. This work was supported by grants from the NIH (NEPRC base grant P51 OD011103; R01 AI090735 to R. Paul Johnson) and by the German Research Foundation (research stipend HO 4527/1-1 to Henoch S. Hong). NR 71 TC 10 Z9 11 U1 0 U2 2 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PY 2013 VL 4 AR UNSP 32 DI 10.3389/fimmu.2013.00032 PG 7 WC Immunology SC Immunology GA V38WS UT WOS:000209374100032 PM 23423644 ER PT J AU Li, XL Teng, MK Reinherz, EL Wang, JH AF Li, Xiao-Long Teng, Mai-Kun Reinherz, Ellis L. Wang, Jia-Huai TI Strict major histocompatibility complex molecule class-specific binding by co-receptors enforces MHC-restricted alpha beta TCR recognition during T lineage subset commitment SO FRONTIERS IN IMMUNOLOGY LA English DT Article DE TCR; co-receptor; lineage commitment; structure; thymocyte development AB Since the discovery of co-receptor dependent alpha beta TCR recognition, considerable effort has been spent on elucidating the basis of CD4 and CD8 lineage commitment in the thymus. The latter is responsible for generating mature CD4 helper and CD8a13 cytotoxic T cell subsets. Although CD4(+) and CD8(+) T cell recognition of peptide antigens is known to be MHC class II- and MHC class l-restricted, respectively, the mechanism of single positive (SP) thymocyte lineage commitment from bipotential double-positive (DP) progenitors is not fully elucidated. Classical models to explain thymic CD4 vs. CD8 fate determination have included a stochastic selection model or instructional models. The latter are based either on strength of signal or duration of signal impacting fate. More recently, differential co-receptor gene imprinting has been shown to be involved in expression of transcription factors impacting cytotoxicT cell development. Here, we address commitment from a structural perspective, focusing on the nature of co-receptor binding to MHC molecules. By surveying 58 MHC class II and 224 MHC class I crystal structures in the Protein Data Bank, it becomes clear that CD4 cannot bind to MHC I molecules, nor can CD8 alpha beta or CD8 alpha alpha bind to MHC II molecules. Given that the co-receptor delivers Lck to phosphorylate exposed CD3 ITAMs within a peptide/MHC (pMHC)-ligated TCR complex to initiate cell signaling, this strict co-receptor recognition fosters MHC class-restricted SP thymocyte lineage commitment at the DP stage even though both co-receptors are expressed on a single cell. In short, the binding preference of an alpha beta TCR for a peptide complexed with an MHC molecule dictates which co-receptor subsequently binds, thereby supporting development of that subset lineage. How function within the lineage is linked further to biopotential fate determination is discussed. C1 [Li, Xiao-Long; Teng, Mai-Kun; Wang, Jia-Huai] Univ Sci & Technol China, Sch Life Sci, Hefei 230026, Peoples R China. [Li, Xiao-Long; Wang, Jia-Huai] Peking Univ, Coll Life Sci, Beijing 100871, Peoples R China. [Reinherz, Ellis L.; Wang, Jia-Huai] Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02215 USA. RP Wang, JH (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, 450 Brookline Ave,SM-1036B, Boston, MA 02215 USA. EM jwang@red.dfci.harvard.edu FU Ministry of Education of China; NIH [HL48675, AI19807, AI100643]; CNNSF [31130018]; CMST [2012CB917200] FX This work was supported by Ministry of Education of China and NIH grant HL48675 to Jia-Huai Wang, NIH grants AI19807 and AI100643 to Ellis L. Reinherz and CNNSF grant 31130018 and CMST grant 2012CB917200 to Mai-Kun Teng. NR 59 TC 4 Z9 4 U1 0 U2 2 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PY 2013 VL 4 AR UNSP 383 DI 10.3389/fimmu.2013.00383 PG 8 WC Immunology SC Immunology GA V38WS UT WOS:000209374100373 PM 24319443 ER PT J AU Ott, PA Bhardwaj, N AF Ott, Patrick A. Bhardwaj, Nina TI Impact of MAPK pathway activation in BRAF(V600) melanoma on T cell and dendritic cell function SO FRONTIERS IN IMMUNOLOGY LA English DT Review DE melanoma; dendritic cell; T cell; BRAF; MEK; immunotherapy; kinase inhibitor AB Constitutive upregulation of the MAPK pathway by a BRAFv600 mutation occurs in about half of melanomas. This leads to increased oncogenic properties such as tumor cell invasion, metastatic potential, and resistance to apoptosis. Blockade of the MAPK pathway with highly specific kinase inhibitors induces unprecedented tumor response rates in patients with advanced BRAFv600 mutant melanoma. Immune checkpoint blockade with monoclonal antibodies targeting cytotoxicT-lymphocyte antigen 4 and programed death-l/PD-L1 has also demonstrated striking anti-tumor activity in patients with advanced melanoma. Tumor responses are likely limited by multiple additional layers of immune suppression in the tumor microenvironment.There is emerging preclinical and clinical evidence suggesting that MARK inhibition has a beneficial effect on the immunosuppressive tumor microenvironment, providing a strong rationale for combined immunotherapy and MARK pathway inhibition in melanoma.The T cell response has been the main focus in the studies reported to date. Since dendritic cells (DCs) are important in the induction of tumor-specific T cell responses, the impact of MARK pathway activation in melanoma on DC function is critical for the melanoma directed immune response. BRAF V600E melanoma cells modulate DCs through the MARK pathway because its blockade in melanoma cells can reverse suppression of DC function. As both MEK/B RAF inhibition and immune checkpoint blockade have recently taken center stage in the treatment of melanoma, a deeper understanding of how MARK pathway inhibition affects the tumor immune response is needed. C1 [Ott, Patrick A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Bhardwaj, Nina] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY 10029 USA. RP Bhardwaj, N (reprint author), Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol & Oncol, Hess Ctr Sci & Med, 1470 Madison Ave Room 116, New York, NY 10029 USA. EM nina.bhardwaj@mssm.edu NR 53 TC 15 Z9 16 U1 2 U2 3 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PY 2013 VL 4 AR UNSP 346 DI 10.3389/fimmu.2013.00346 PG 7 WC Immunology SC Immunology GA V38WS UT WOS:000209374100340 PM 24194739 ER PT J AU Wang, JH Reinherz, EL AF Wang, Jia-Huai Reinherz, Ellis L. TI Revisiting the putative TCR C alpha dimerization model through structural analysis SO FRONTIERS IN IMMUNOLOGY LA English DT Article DE TCR; receptor dimerizat ion; signal transduction; structural immunology AB Despite major advances in T cell receptor (TCR) biology and structure, how peptide MHC complex (pMHC) ligands trigger alpha beta TCR activation remains unresolved. Two views exist. One model postulates that monomeric TCR pMHC ligation events are sufficient while a second proposes that TCR TCR dimerization in cis via C alpha domain interaction plus pMHC binding is critical. We scrutinized 22 known TCR/pMHC complex crystal structures, and did not find any predicted molecular C alpha-C alpha contacts in these crystals that would allow for physiological TCR dimerization. Moreover, the presence of conserved glycan adducts on the outer face of the C alpha domain preclude the hypothesized TCR dimerization through the C alpha domain. Observed functional consequences of C alpha mutations are likely indirect, with TCR microclusters at the immunological synapse driven by TCR transmembrane/cytoplasmic interactions via signaling molecules, scaffold proteins, and/or cytoskeletal elements. C1 [Wang, Jia-Huai; Reinherz, Ellis L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lab Immunobiol,Dept Med Oncol, Boston, MA 02215 USA. [Wang, Jia-Huai] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02215 USA. [Wang, Jia-Huai] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02215 USA. [Reinherz, Ellis L.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Wang, JH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Lab Immunobiol,Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM jwang@red.dfci.harvard.edu FU NIAID NIH HHS [R56 AI019807, R01 AI100643] NR 34 TC 2 Z9 2 U1 0 U2 1 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PY 2013 VL 4 AR UNSP 16 DI 10.3389/fimmu.2013.00016 PG 6 WC Immunology SC Immunology GA V38WS UT WOS:000209374100016 PM 23386853 ER PT J AU Rana, KD Vaina, LM Hamalainen, MS AF Rana, Kunjan D. Vaina, Lucia M. Haemaelaeinen, Matti S. TI A fast statistical significance test for baseline correction and comparative analysis in phase locking SO FRONTIERS IN NEUROINFORMATICS LA English DT Article DE MEG; phase locking; oscillation; cross-talk; circular statistics AB Human perception, cognition, and action are supported by a complex network of interconnected brain regions. There is an increasing interest in measuring and characterizing these networks as a function of time and frequency, and inter-areal phase locking is often used to reveal these networks. This measure assesses the consistency of phase angles between the electrophysiological activity in two areas at a specific time and frequency. Non-invasively, the signals from which phase locking is computed can be measured with magnetoencephalography (MEG) and electroencephalography (EEG). However, due to the lack of spatial specificity of reconstructed source signals in MEG and EEG, inter-areal phase locking may be confounded by false positives resulting from crosstalk. Traditional phase locking estimates assume that no phase locking exists when the distribution of phase angles is uniform. However, this conjecture is not true when crosstalk is present. We propose a novel method to improve the reliability of the phase-locking measure by sampling phase angles from a baseline, such as from a prestimulus period or from resting-state data, and by contrasting this distribution against one observed during the time period of interest. C1 [Rana, Kunjan D.; Vaina, Lucia M.] Boston Univ, Dept Biomed Engn, Brain & Vis Res Lab, Boston, MA 02215 USA. [Vaina, Lucia M.; Haemaelaeinen, Matti S.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Vaina, Lucia M.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Vaina, LM (reprint author), Boston Univ, Dept Biomed Engn, Brain & Vis Res Lab, 44 Cummington St, Boston, MA 02215 USA. EM vaina@bu.edu RI Hamalainen, Matti/C-8507-2013 FU NIH-National Institute on Drug Abuse [T90DA032484]; National Institutes of Health [RO1NS064100, P41RR14075, 1R01EB009048] FX We thank the two reviewers for their thoughtful and careful comments and suggestions that helped improve the clarity of the work presented here. Kunjan D. Rana was supported in part by Award Number T90DA032484 from the NIH-National Institute on Drug Abuse. Lucia M. Vaina and Kunjan D. Rana were supported in part by RO1NS064100 from the National Institutes of Health. Matti S. Hamalainen was supported in part by P41RR14075 and 1R01EB009048 from the National Institutes of Health. NR 34 TC 2 Z9 2 U1 0 U2 3 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5196 J9 FRONT NEUROINFORM JI Front. Neuroinformatics PY 2013 VL 7 AR UNSP 3 DI 10.3389/fninf.2013.00003 PG 10 WC Mathematical & Computational Biology; Neurosciences SC Mathematical & Computational Biology; Neurosciences & Neurology GA V36JA UT WOS:000209207300003 PM 23919088 ER PT J AU Khanna, A Venteicher, AS Walcott, BP Kahle, KT Mordes, DA William, CM Ghogawala, Z Ogilvy, CS AF Khanna, Arjun Venteicher, Andrew S. Walcott, Brian P. Kahle, Kristopher T. Mordes, Daniel A. William, Christopher M. Ghogawala, Zoher Ogilvy, Christopher S. TI Glioblastoma mimicking an arteriovenous malformation SO FRONTIERS IN NEUROLOGY LA English DT Article DE glioblastoma; astrocytoma; subarachnoid hemorrhage; intraparenchymal hemorrhage; angiography; arteriovenous malformation AB Abnormal cerebral vasculature can be a manifestation of a vascular malformation or a neoplastic process. We report the case of a patient with angiography-negative subarachnoid hemorrhage (SAH) who re-presented 3 years later with a large intraparenchymal hemorrhage. Although imaging following the intraparenchymal hemorrhage was suggestive of arteriovenous malformation, the patient was ultimately found to have an extensive glioblastoma associated with abnormal tumor vasculature. The case emphasizes the need for magnetic resonance imaging to investigate angiography-negative SAH in suspicious cases to rule out occult etiologies, such as neoplasm. We also discuss diagnostic pitfalls when brain tumors are associated with hemorrhage and abnormal vasculature. C1 [Khanna, Arjun; Venteicher, Andrew S.; Walcott, Brian P.; Kahle, Kristopher T.; Mordes, Daniel A.; William, Christopher M.; Ogilvy, Christopher S.] Harvard Univ, Sch Med, Boston, MA USA. [Venteicher, Andrew S.; Walcott, Brian P.; Kahle, Kristopher T.; Ogilvy, Christopher S.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Mordes, Daniel A.; William, Christopher M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ghogawala, Zoher] Tufts Univ, Sch Med, Lahey Hosp, Dept Neurosurg, Burlington, MA USA. [Ghogawala, Zoher] Tufts Univ, Sch Med, Med Ctr, Burlington, MA USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, 55 Fruit St,White Bldg Room 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu OI William, Christopher/0000-0001-8933-1639 FU NINDS NIH HHS [K08 NS069811] NR 37 TC 1 Z9 1 U1 0 U2 0 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-2295 J9 FRONT NEUROL JI Front. Neurol. PY 2013 VL 4 AR 144 DI 10.3389/fneur.2013.00144 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V42QT UT WOS:000209629000143 PM 24137154 ER PT J AU Khanna, A Walcott, BP Kahle, KT AF Khanna, Arjun Walcott, Brian Patrick Kahle, Kristopher T. TI Limitations of current GABA agonists in neonatal seizures: toward GABA modulation via the targeting of neuronal Cl- transport SO FRONTIERS IN NEUROLOGY LA English DT Review DE seizure; GABA; neonatal seizure; bumetanide; NKCC1; KCC2; WNK kinase; SPAK/OSR1 kinase AB Neonatal intensive care has advanced rapidly in the last 40 years, with dramatic decreases in mortality and morbidity; however, for neonatal seizures, neither therapies nor outcomes have changed significantly. Basic and clinical studies indicate that seizures in neonates have long-term neurodevelopmental and psychiatric consequences, highlighting the need for novel pharmacotherapeutics. First-line treatments targeting GABAA receptors, like barbiturates and benzodiazepines, are limited in their efficacy and carry significant risks to the developing brain. Here, we review the use of current GABA agonist therapies for neonatal seizures and suggest other treatment strategies given recent developments in the understanding of disease pathogenesis. One promising avenue is the indirect manipulation of the GABAergic system, via the modulation of neuronal Cl- gradients, by targeting the cation-Cl cotransporters (NKCC1 and KCC2) or their regulatory signaling molecules. This strategy might yield a novel class of more efficacious anti-epileptics with fewer side effects by specifically addressing disease pathophysiology. Moreover, this strategy may have ramifications for other adult seizure syndromes in which GABA receptor-mediated depolarizations play a pathogenic role, such as temporal lobe epilepsy. C1 [Khanna, Arjun; Walcott, Brian Patrick; Kahle, Kristopher T.] Harvard Univ, Sch Med, Dept Surg, Div Neurosurg,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Kahle, Kristopher T.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA USA. RP Kahle, KT (reprint author), Harvard Univ, Sch Med, Dept Neurol Surg, Massachusetts Gen Hosp, 55 Fruit St,White Bldg Room 502, Boston, MA 02114 USA. EM kkahle@enders.tch.harvard.edu NR 80 TC 10 Z9 11 U1 1 U2 3 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-2295 J9 FRONT NEUROL JI Front. Neurol. PY 2013 VL 4 AR 78 DI 10.3389/fneur.2013.00078 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V42QT UT WOS:000209629000077 PM 23805124 ER PT J AU Nagenthiraja, K Walcott, BP Hansen, MB Ostergaard, L Mouridsen, K AF Nagenthiraja, Kartheeban Walcott, Brian P. Hansen, Mikkel B. Ostergaard, Leif Mouridsen, Kim TI Automated decision-support system for prediction of treatment responders in acute ischemic stroke SO FRONTIERS IN NEUROLOGY LA English DT Article DE stroke; brain edema; magnetic resonance imaging; brain ischemia; decision-support systems; clinical; thrombolytic therapy AB MRI is widely used in the assessment of acute ischemic stroke. In particular, it identifies the mismatch between hypoperf used and the permanently damaged tissue, the PWI-DWI mismatch volume. It is used to help triage patients into active or supportive treatment pathways. COMBAT Stroke is an automated software tool for estimating the mismatch volume and ratio based on MRI. Herein, we validate the decision made by the software with actual clinical decision rendered. Furthermore, we evaluate the association between treatment decisions (both automated and actual) and outcomes. COMBAT Stroke was used to determine PWI-DWI mismatch volume and ratio in 228 patients from two European multi-center stroke databases. We performed confusion matrix analysis to summarize the agreement between the automated selection and the clinical decision. Finally, we evaluated the clinical and imaging outcomes of the patients in the four entries of the confusion matrix (true positive, true negative, false negative, and false positive). About 186 of 228 patients with acute stroke underwent thrombolytic treatment, with the remaining 42 receiving supportive treatment only. Selection based on radiographic criteria using COMBAT Stroke classified 142 patients as potential candidates for thrombolytic treatment and 86 for supportive treatment; 60% sensitivity and 29% specificity. The patients deemed eligible for thrombolytic treatment by COMBAT Stroke demonstrated significantly higher rates of compromised tissue salvage, less neurological deficit, and were more likely to experience thrombus dissolving and reestablishment of normal blood flow at 24 h follow-up compared to those who were treated without substantial PWI-DWI mismatch. These results provide evidence that COMBAT Stroke, in addition to clinical assessment, may offer an optimal framework for a fast, efficient, and standardized clinical support tool to select patients for thrombolysis in acute ischemic stroke. C1 [Nagenthiraja, Kartheeban; Hansen, Mikkel B.; Ostergaard, Leif; Mouridsen, Kim] Aarhus Univ, Ctr Funct Integrat Neurosci, Aarhus, Denmark. [Nagenthiraja, Kartheeban; Hansen, Mikkel B.; Ostergaard, Leif; Mouridsen, Kim] Aarhus Univ, MINDLab, Aarhus, Denmark. [Nagenthiraja, Kartheeban] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Nagenthiraja, Kartheeban; Walcott, Brian P.] Harvard Univ, Sch Med, Boston, MA USA. [Walcott, Brian P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Walcott, Brian P.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Walcott, Brian P.] Harvard Univ, Sch Med, Charlestown, MA USA. RP Nagenthiraja, K (reprint author), Athinoula A Martinos Ctr Biomed Imaging, 149 Thirteenth St,Suite 2301, Charlestown, MA 02129 USA. EM knag@cfin.dk RI Hansen, Mikkel/A-5899-2009; Ostergaard, Leif/A-9281-2008 OI Hansen, Mikkel/0000-0002-8619-1519; Ostergaard, Leif/0000-0003-2930-6997 FU Danish National Research Foundation; Danish Agency for Science, Technology and Innovation; European Commission [027294] FX The authors wish to thank the Danish National Research Foundation (Leif Ostergaard, Kim Mouridsen), The Danish Agency for Science, Technology and Innovation (Mikkel B. Hansen, Leif Ostergaard, Kim Mouridsen) and the European Commission's 6th Framework Programme (Contract No. 027294) (Kartheeban Nagenthiraja, Leif Ostergaard) for financial support. We thank Dr. Irene Mikkelsen, Dr. Niels Hjort, Prof. Grethe Andersen, Dr. Tae-Hee Cho, Prof. Norbert Nighoghossian, Dr. Susanne Siemonsen Prof. Jens Fiehler, Dr. Josep Puig Alcantara, Prof. Salva Pedraza, Dr. Josef Alawneh, and Prof. Jean-Claude Baron for access to patient data. NR 28 TC 0 Z9 0 U1 0 U2 3 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-2295 J9 FRONT NEUROL JI Front. Neurol. PY 2013 VL 4 AR 140 DI 10.3389/fneur.2013.00140 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V42QT UT WOS:000209629000139 PM 24133479 ER PT J AU Yang, C Franciosi, S Brown, RE AF Yang, Chun Franciosi, Serena Brown, Ritchie E. TI Adenosine inhibits the excitatory synaptic inputs to basal forebrain cholinergic, GABAergic, and parvalbumin neurons in mice SO FRONTIERS IN NEUROLOGY LA English DT Article DE patch-clamp; adenosine A1 receptor; presynaptic modulation; sleep; transgenic mice AB Coffee and tea contain the stimulants caffeine and theophylline. These compounds act as antagonists of adenosine receptors. Adenosine promotes sleep and its extracellular concentration rises in association with prolonged wakefulness, particularly in the basal fore-brain (BF) region involved in activating the cerebral cortex. However, the effect of adenosine on identified BF neurons, especially non-cholinergic neurons, is incompletely understood. Here we used whole-cell patch-clamp recordings in mouse brain slices prepared from two validated transgenic mouse lines with fluorescent proteins expressed in GABAergic or parvalbumin (PV) neurons to determine the effect of adenosine. Whole-cell recordings were made from BF cholinergic neurons and from BF GABAergic and PV neurons with the size (>20 mu m) and intrinsic membrane properties (prominent H-currents) corresponding to cortically projecting neurons. A brief (2 min) bath application of adenosine (100 mu M) decreased the frequency but not the amplitude of spontaneous excitatory postsynaptic currents (EPSCs) in all groups of BF cholinergic, GABAergic, and PV neurons we recorded. In addition, adenosine decreased the frequency of miniature EPSCs in BF cholinergic neurons. Adenosine had no effect on the frequency of spontaneous inhibitory postsynaptic currents in cholinergic neurons or GABAergic neurons with large H-currents but reduced them in a group of GABAergic neurons with smaller H-currents. All effects of adenosine were blocked by a selective, adenosine A1 receptor antagonist, cyclopentyltheophylline (CPT, 1 mu M). Adenosine had no postsynaptic effects. Taken together, our work suggests that adenosine promotes sleep by an A1 receptor-mediated inhibition of glutamatergic inputs to cortically projecting cholinergic and GABA/PV neurons. Conversely, caffeine and theophylline promote attentive wakefulness by inhibiting these A1 receptors in BF thereby promoting the high-frequency oscillations in the cortex required for attention and cognition. C1 [Yang, Chun; Franciosi, Serena; Brown, Ritchie E.] Harvard Univ, Sch Med, Dept Psychiat, Lab Neurosci,VA Boston Healthcare Syst, Brockton, MA 02401 USA. [Franciosi, Serena] Univ Milan, Sch Med, Inst Human Physiol 2, Milan, Italy. RP Brown, RE (reprint author), Harvard Univ, Sch Med, VA Med Ctr Brockton,Res 151C, Neurophysiol Lab,Dept Psychiat,VA Boston Healthca, 940 Belmont St, Brockton, MA 02301 USA. EM ritchie_brown@hms.harvard.edu OI Brown, Ritchie/0000-0002-7164-4132 FU VA; NIMH [R01 MH039683, R21 MH094803] FX This work was supported by VA, by NIMH R01 MH039683 (to R. W. McCarley) and by NIMH R21 MH094803 (to Ritchie E. Brown). NR 54 TC 8 Z9 8 U1 2 U2 5 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-2295 J9 FRONT NEUROL JI Front. Neurol. PY 2013 VL 4 AR 77 DI 10.3389/fneur.2013.00077 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V42QT UT WOS:000209629000076 PM 23801984 ER PT J AU Young, AMH Karri, SK Ogilvy, CS Zhao, NH AF Young, Adam M. H. Karri, Surya K. Ogilvy, Christopher S. Zhao, Ninghui TI Is there a role for treating inflammation in moyamoya disease?: a review of histopathology, genetics, and signaling cascades SO FRONTIERS IN NEUROLOGY LA English DT Review DE moyamoya; brain; inflammation; genetics AB Moyamoya disease is a slowly progressing steno-occlusive condition affecting the cerebrovasculature. Affecting the terminal internal carotid arteries (ICA) and there branches, bilaterally, a resulting in a fine vascular network in the base of the brain to allow for compensation of the stenosed vessels. While there is obvious evidence of the involvement of inflammatory proteins in the condition, this has historically not been acknowledged as a causal factor. Here we describe the fundamental histopathology, genetics, and signaling cascades involved in moyamoya and debate whether these factors can be linked as causal factor for the condition or whether they are simply a secondary result of the ischemia described in the condition. A particular focus has been placed on the multitude of signaling cascades linked to the condition as these are viewed as having the greatest therapeutic potential. As such we hope to draw some novel insight into potential diagnostic and therapeutic inflammatory targets in the condition. C1 [Young, Adam M. H.; Karri, Surya K.; Ogilvy, Christopher S.; Zhao, Ninghui] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. [Young, Adam M. H.] Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, Hills Rd, Cambridge CB2 0SP, England. RP Young, AMH (reprint author), Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, Hills Rd, Cambridge CB2 0SP, England. EM ay276@cam.ac.uk NR 55 TC 5 Z9 5 U1 2 U2 3 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-2295 J9 FRONT NEUROL JI Front. Neurol. PY 2013 VL 4 AR 105 DI 10.3389/fneur.2013.00105 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V42QT UT WOS:000209629000104 PM 23966972 ER PT J AU Gallun, FJ Diedesch, AC Kampel, SD Jakien, KM AF Gallun, Frederick J. Diedesch, Anna C. Kampel, Sean D. Jakien, Kasey M. TI Independent impacts of age and hearing loss on spatial release in a complex auditory environment SO FRONTIERS IN NEUROSCIENCE LA English DT Article DE spatial release; aging; hearing loss; virtual spatial array ID TEMPORAL FINE-STRUCTURE; IMPAIRED LISTENERS; BINAURAL HEARING; INFORMATIONAL MASKING; FREQUENCY-SELECTIVITY; INTERAURAL PHASE; COCKTAIL-PARTY; SPEECH; NOISE; SEPARATION AB Listeners in complex auditory environments can benefit from the ability to use a variety of spatial and spectrotemporal cues for sound source segregation. Probing these abilities is an essential part of gaining a more complete understanding of why listeners differ in navigating the auditory environment. Two fundamental processes that can impact the auditory systems of individual listeners are aging and hearing loss. One difficulty with uncovering the independent effects of age and hearing loss on spatial release is the commonly observed phenomenon of age-related hearing loss. In order to reveal the effects of aging on spatial hearing, it is essential to develop testing methods that reduce the influence of hearing loss on the outcomes. The statistical power needed for such testing generally requires a larger number of participants than can easily be tested using traditional behavioral methods. This work describes the development and validation of a rapid method by which listeners can be categorized in terms of their ability to use spatial and spectrotemporal cues to separate competing speech streams. Results show that when age and audibility are not covarying, age alone can be shown to substantially reduce spatial release from masking. These data support the hypothesis that aging, independent of an individual's hearing threshold, can result in changes in the cortical and/or subcortical structures essential for spatial hearing. C1 [Gallun, Frederick J.; Kampel, Sean D.] Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Dept Vet Affairs, Portland, OR 97239 USA. [Gallun, Frederick J.; Jakien, Kasey M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Diedesch, Anna C.] Vanderbilt Univ, Nashville, TN 37235 USA. RP Gallun, FJ (reprint author), Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Dept Vet Affairs, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM Frederick.Gallun@va.gov FU Department of Veterans Affairs Rehabilitation Research and Development Service [C4963W]; National Institutes of Health's National Institute for Deafness and Communication Disorders [R01 DC011828] FX We are grateful to the many participants, both Veterans and non-Veterans, who volunteered their time to this study. Assistance in the areas of data collection, database management, and compliance assurance was rendered by Erin Conner, Patrick Tsukuda, and Sara Blankenship. The work was supported by the Department of Veterans Affairs Rehabilitation Research and Development Service (Career Development Award C4963W) and the National Institutes of Health's National Institute for Deafness and Communication Disorders (R01 DC011828). The work was supported with resources and the use of facilities at VA RR&D National Center for Rehabilitative Auditory Research, which is located at the Portland VA Medical Center. The contents of this article are the private views of the authors and should not be assumed to represent the views of the Department of Veterans Affairs or the United States Government. NR 37 TC 11 Z9 11 U1 0 U2 6 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-453X J9 FRONT NEUROSCI-SWITZ JI Front. Neurosci. PY 2013 VL 7 AR 252 DI 10.3389/fnins.2013.00252 PG 11 WC Neurosciences SC Neurosciences & Neurology GA AW9HF UT WOS:000346567300248 PM 24391535 ER PT J AU Gramfort, A Luessi, M Larson, E Engemann, DA Strohmeier, D Brodbeck, C Goj, R Jas, M Brooks, T Parkkonen, L Hamalainen, M AF Gramfort, Alexandre Luessi, Martin Larson, Eric Engemann, Denis A. Strohmeier, Daniel Brodbeck, Christian Goj, Roman Jas, Mainak Brooks, Teon Parkkonen, Lauri Haemaelaeinen, Matti TI MEG and EEG data analysis with MNE-Python SO FRONTIERS IN NEUROSCIENCE LA English DT Article DE electroencephalography (EEG); magnetoencephalography (MEG); neuroimaging; software; python; open-source ID INDEPENDENT COMPONENT ANALYSIS; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; HUMAN BRAIN; FMRI; RECONSTRUCTION; COMPUTATION; DIPOLE; SYSTEM AB Magnetoencephalography and electroencephalography (M/EEG) measure the weak electromagnetic signals generated by neuronal activity in the brain. Using these signals to characterize and locate neural activation in the brain is a challenge that requires expertise in physics, signal processing, statistics, and numerical methods. As part of the MNE software suite, MNE-Python is an open-source software package that addresses this challenge by providing state-of-the-art algorithms implemented in Python that cover multiple methods of data preprocessing, source localization, statistical analysis, and estimation of functional connectivity between distributed brain regions. All algorithms and utility functions are implemented in a consistent manner with well-documented interfaces, enabling users to create M/EEG data analysis pipelines by writing Python scripts. Moreover, MNE-Python is tightly integrated with the core Python libraries for scientific comptutation (NumPy, SciPy) and visualization (matplotlib and Mayavi), as well as the greater neuroimaging ecosystem in Python via the Nibabel package. The code is provided under the new BSD license allowing code reuse, even in commercial products. Although MNE-Python has only been under heavy development for a couple of years, it has rapidly evolved with expanded analysis capabilities and pedagogical tutorials because multiple labs have collaborated during code development to help share best practices. MNE-Python also gives easy access to preprocessed datasets, helping users to get started quickly and facilitating reproducibility of methods by other researchers. Full documentation, including dozens of examples, is available at http://martinos.org/mne. C1 [Gramfort, Alexandre] Telecom ParisTech, CNRS LTCI, Inst Mines Telecom, F-75014 Paris, France. [Gramfort, Alexandre; Luessi, Martin; Haemaelaeinen, Matti] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Gramfort, Alexandre; Luessi, Martin; Haemaelaeinen, Matti] Harvard Univ, Sch Med, Charlestown, MA USA. [Gramfort, Alexandre] CEA Saclay, NeuroSpin, F-91191 Gif Sur Yvette, France. [Larson, Eric] Univ Washington, Inst Learning & Brain Sci, Seattle, WA 98195 USA. [Engemann, Denis A.] Forschungszentrum Juelich, Inst Neurosci & Med Cognit Neurosci INM 3, Julich, Germany. [Engemann, Denis A.] Univ Hosp, Dept Psychiat, Brain Imaging Lab, Cologne, Germany. [Strohmeier, Daniel] Ilmenau Univ Technol, Inst Biomed Engn & Informat, Ilmenau, Germany. [Brodbeck, Christian; Brooks, Teon] NYU, Dept Psychol, New York, NY 10003 USA. [Goj, Roman] Univ Stirling, Sch Nat Sci, Psychol Imaging Lab, Stirling FK9 4LA, Scotland. [Jas, Mainak; Parkkonen, Lauri] Aalto Univ, Sch Sci, Dept Biomed Engn & Computat Sci, Espoo, Finland. [Jas, Mainak; Parkkonen, Lauri; Haemaelaeinen, Matti] Aalto Univ, Sch Sci, Brain Res Unit, OV Lounasmaa Lab, Espoo, Finland. RP Gramfort, A (reprint author), Telecom ParisTech, CNRS LTCI, Inst Mines Telecom, 37-39 Rue Dareau, F-75014 Paris, France. EM alexandre.gramfort@telecom-paristech.fr RI Hamalainen, Matti/C-8507-2013; Parkkonen, Lauri/G-6755-2012; OI Parkkonen, Lauri/0000-0002-0130-0801; Brooks, Teon L/0000-0001-7344-3230 FU National Institute of Biomedical Imaging and Bioengineering [5R01EB009048, P41RR014075]; National Institute on Deafness and Other Communication Disorders fellowship [F32DC012456]; NSF [0958669, 1042134]; Swiss National Science Foundation Early Postdoc; Mobility fellowship [148485]; NYUAD Institute [G1001]; National Science Foundation Graduate Research Fellowship [DGE-1342536]; "aivoAALTO" program; German Research Foundation [Ha 2899/8-2]; [ERC-YStG-263584] FX This work was supported by National Institute of Biomedical Imaging and Bioengineering grants 5R01EB009048 and P41RR014075, National Institute on Deafness and Other Communication Disorders fellowship F32DC012456, and NSF awards 0958669 and 1042134. The work of Alexandre Gramfort was partially supported by ERC-YStG-263584. Martin Luessi was partially supported by the Swiss National Science Foundation Early Postdoc. Mobility fellowship 148485. Christian Brodbeck was supported by grant G1001 from the NYUAD Institute. Teon Brooks was supported by the National Science Foundation Graduate Research Fellowship under Grant No. DGE-1342536. Lauri Parkkonen was supported by the "aivoAALTO" program. Daniel Strohmeier was supported by grant Ha 2899/8-2 from the German Research Foundation. NR 56 TC 44 Z9 44 U1 0 U2 7 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-453X J9 FRONT NEUROSCI-SWITZ JI Front. Neurosci. PY 2013 VL 7 AR 267 DI 10.3389/fnins.2013.00267 PG 13 WC Neurosciences SC Neurosciences & Neurology GA AW9HF UT WOS:000346567300262 PM 24431986 ER PT J AU Turner, JA Damaraju, E van Erp, TM Mathalon, DH Ford, JM Voyvodic, J Mueller, BA Belger, A Bustillo, J McEwen, S Potkin, SG Calhoun, VD AF Turner, Jessica A. Damaraju, Eswar van Erp, Theog. M. Mathalon, Daniel H. Ford, Judith M. Voyvodic, James Mueller, Bryon A. Belger, Aysenil Bustillo, Juan McEwen, Sarah Potkin, Steven G. Calhoun, Vince D. CA FBIRN TI A multi-site resting state fMRI study on the amplitude of low frequency fluctuations in schizophrenia SO FRONTIERS IN NEUROSCIENCE LA English DT Article DE resting state fMRI; LFO; ALFF; schizophrenia; multi-site studies; effect size ID INDEPENDENT COMPONENT ANALYSIS; LINE BRAIN ACTIVITY; FUNCTIONAL CONNECTIVITY; WORKING-MEMORY; CORTICAL NETWORKS; MULTICENTER FMRI; TEST-RETEST; MRI; RELIABILITY; NOISE AB Background: This multi-site study compares resting state fMRI amplitude of low frequency fluctuations (ALFF) and fractional ALFF (fALFF) between patients with schizophrenia (SZ) and healthy controls (HC). Methods: Eyes-closed resting fMRI scans (5:38 min; n = 306, 146 SZ) were collected from 6 Siemens 3T scanners and one GE 3T scanner. Imaging data were pre-processed using an SPM pipeline. Power in the low frequency band (0.01-0.08 Hz) was calculated both for the original pre-processed data as well as for the pre-processed data after regressing out the six rigid-body motion parameters, mean white matter (WM) and cerebral spinal fluid (CSF) signals. Both original and regressed ALFF and fALFF measures were modeled with site, diagnosis, age, and diagnosis x age interactions. Results: Regressing out motion and non-gray matter signals significantly decreased fALFF throughout the brain as well as ALFF in the cortical edge, but significantly increased ALFF in subcortical regions. Regression had little effect on site, age, and diagnosis effects on ALFF, other than to reduce diagnosis effects in subcortical regions. There were significant effects of site across the brain in all the analyses, largely due to vendor differences. HC showed greater ALFF in the occipital, posterior parietal, and superior temporal lobe, while SZ showed smaller clusters of greater ALFF in the frontal and temporal/insular regions as well as in the caudate, putamen, and hippocampus. HC showed greater fALFF compared with SZ in all regions, though subcortical differences were only significant for original fALFF. Conclusions: SZ show greater eyes-closed resting state low frequency power in frontal cortex, and less power in posterior lobes than do HC; fALFF, however, is lower in SZ than HC throughout the cortex. These effects are robust to multi-site variability. Regressing out physiological noise signals significantly affects both total and fALFF measures, but does not affect the pattern of case/control differences. C1 [Turner, Jessica A.; Damaraju, Eswar; Calhoun, Vince D.] Mission Res Network, Albuquerque, NM 87106 USA. [Turner, Jessica A.; Bustillo, Juan; Calhoun, Vince D.] Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. [van Erp, Theog. M.; Potkin, Steven G.; FBIRN] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA USA. [Mathalon, Daniel H.; Ford, Judith M.] Univ San Francisco, Dept Psychiat, San Francisco, CA 94117 USA. [Mathalon, Daniel H.; Ford, Judith M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Voyvodic, James] Duke Univ, Brain Imaging & Anal Ctr, Dept Radiol, Durham, NC USA. [Mueller, Bryon A.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Belger, Aysenil] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC USA. [McEwen, Sarah] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA USA. [Calhoun, Vince D.] Univ New Mexico, Albuquerque, NM 87131 USA. RP Turner, JA (reprint author), Mission Res Network, 1101 Yale Blvd NE, Albuquerque, NM 87106 USA. EM jturner@mrn.org RI Turner, Jessica/H-7282-2015; OI Turner, Jessica/0000-0003-0076-8434; Belger, Aysenil/0000-0003-2687-1966; Potkin, Steven/0000-0003-1028-1013 FU NIH [U24 RR021992]; NIGMS [U24 GM104203]; DOE [DE-FG02-08ER64581] FX We gratefully acknowledge Ravi Kalyanam and Srinivas Rachakonda for their help in the paired t-test code, and Bryan Galindro for initial ALFF analyses on subsets of these data. Many of the figures were prepared using the Mricron software (http://www.mccauslandcenter.sc.edu/mricro/mricron/). This work was supported by awards from NIH, U24 RR021992 to the Functional Imaging Biomedical Informatics Research Network (FBIRN, http://www.birncommunity.org), NIGMS grant U24 GM104203 to the Bio-Informatics Research Network Coordinating Center (BIRN-CC), and DOE grant DE-FG02-08ER64581. NR 68 TC 30 Z9 34 U1 10 U2 17 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-453X J9 FRONT NEUROSCI-SWITZ JI Front. Neurosci. PY 2013 VL 7 AR 137 DI 10.3389/fnins.2013.00137 PG 13 WC Neurosciences SC Neurosciences & Neurology GA AW9HF UT WOS:000346567300136 PM 23964193 ER PT J AU Lee, AKC Rajaram, S Xia, J Bharadwaj, H Larson, E Hamalainen, MS Shinn-Cunningham, BG AF Lee, Adrian K. C. Rajaram, Siddharth Xia, Jing Bharadwaj, Hari Larson, Eric Haemaelaeinen, Matti S. Shinn-Cunningham, Barbara G. TI Auditory selective attention reveals preparatory activity in different cortical regions for selection based on source location and source pitch SO FRONTIERS IN NEUROSCIENCE LA English DT Article DE frontal eye fields; superior temporal sulcus; magnetoencephalography; auditory attention; auditory spatial processing; pitch processing ID SUPERIOR TEMPORAL SULCUS; SPATIAL ATTENTION; VISUAL-CORTEX; EYE-MOVEMENTS; BRAIN; SPACE; MECHANISMS; FMRI; EEG; MEG AB In order to extract information in a rich environment, we focus on different features that allow us to direct attention to whatever source is of interest. The cortical network deployed during spatial attention, especially in vision, is well characterized. For example, visuospatial attention engages a frontoparietal network including the frontal eye fields (FEFs), which modulate activity in visual sensory areas to enhance the representation of an attended visual object. However, relatively little is known about the neural circuitry controlling attention directed to non-spatial features, or to auditory objects or features (either spatial or non-spatial). Here, using combined magnetoencephalography (MEG) and anatomical information obtained from MRI, we contrasted cortical activity when observers attended to different auditory features given the same acoustic mixture of two simultaneous spoken digits. Leveraging the fine temporal resolution of MEG, we establish that activity in left FEE is enhanced both prior to and throughout the auditory stimulus when listeners direct auditory attention to target location compared to when they focus on target pitch. In contrast, activity in the left posterior superior temporal sulcus (STS), a region previously associated with auditory pitch categorization, is greater when listeners direct attention to target pitch rather than target location. This differential enhancement is only significant after observers are instructed which cue to attend, but before the acoustic stimuli begin. We therefore argue that left FEF participates more strongly in directing auditory spatial attention, while the left STS aids auditory object selection based on the non-spatial acoustic feature of pitch. C1 [Lee, Adrian K. C.; Bharadwaj, Hari; Haemaelaeinen, Matti S.] Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Lee, Adrian K. C.; Larson, Eric] Univ Washington, Inst Learning & Brain Sci, Dept Speech & Hearing Sci, Seattle, WA 98195 USA. [Lee, Adrian K. C.; Rajaram, Siddharth; Xia, Jing; Bharadwaj, Hari; Shinn-Cunningham, Barbara G.] Boston Univ, Ctr Computat Neurosci & Neural Technol, Boston, MA 02215 USA. [Bharadwaj, Hari; Shinn-Cunningham, Barbara G.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. RP Lee, AKC (reprint author), Univ Washington, Portage Bay Bldg Box 357988,1715 NE Columbia Rd, Seattle, WA 98195 USA. EM akclee@alum.mit.edu OI Larson, Eric/0000-0003-4782-5360; Lee, Adrian KC/0000-0002-7611-0500; Bharadwaj, Hari/0000-0001-8685-9630 FU National Institutes of Health (NIH), an NSSEFF fellowship [P41 RR014075, K99/R00 DC010196]; [T32DC000018] FX We thank Nick Kurkjy for his assistance with data collection. This work was supported by National Institutes of Health (NIH) grants to Adrian K. C. Lee (K99/R00 DC010196) and Matti S. Hamalainen (P41 RR014075), an NSSEFF fellowship to Barbara G. Shinn-Cunningham, and training grant T32DC000018 (Eric Larson). NR 44 TC 11 Z9 11 U1 0 U2 3 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-453X J9 FRONT NEUROSCI-SWITZ JI Front. Neurosci. PY 2013 VL 6 AR 190 DI 10.3389/fnins.2012.00190 PG 9 WC Neurosciences SC Neurosciences & Neurology GA AW9GW UT WOS:000346566400003 ER PT J AU Russell, MD Young, AMH Karri, SK AF Russell, Mark D. Young, Adam M. H. Karri, Surya K. TI Biomarkers of pediatric brain tumors SO FRONTIERS IN PEDIATRICS LA English DT Review DE biomarker; pediatric; brain; tumor; CNS; marker; medulloblastoma AB Background and Need for Novel Biomarkers: Brain tumors are the leading cause of death by solid tumors in children. Although improvements have been made in their radiological detection and treatment, our capacity to promptly diagnose pediatric brain tumors in their early stages remains limited. This contrasts several other cancers where serum biomarkers such as cancer antigen (CA) 19-9 and CA 125 facilitate early diagnosis and treatment. Aim: The aim of this article is to review the latest literature and highlight biomarkers which may be of clinical use in the common types of primary pediatric brain tumor. Methods: A PubMed search was performed to identify studies reporting biomarkers in the bodily fluids of pediatric patients with brain tumors. Details regarding the sample type [serum, cerebrospinal fluid (CSF), or urine], biomarkers analyzed, methodology, tumor type, and statistical significance were recorded. Results: A total of 12 manuscripts reporting 19 biomarkers in 367 patients vs. 397 controls were identified in the literature. Of the 19 biomarkers identified, 12 were isolated from CSF, 2 from serum, 3 from urine, and 2 from multiple bodily fluids. All but one study reported statistically significant differences in biomarker expression between patient and control groups. Conclusion:This review identifies a panel of novel biomarkers for pediatric brain tumors. It provides a platform for the further studies necessary to validate these biomarkers and, in addition, highlights several techniques through which new biomarkers can be discovered. C1 [Russell, Mark D.; Young, Adam M. H.] Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, Box 111,Hills Rd, Cambridge CB2 0SP, England. [Young, Adam M. H.; Karri, Surya K.] Harvard Univ, Harvard Med Sch, Dept Neurosurg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Young, AMH (reprint author), Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, Box 111,Hills Rd, Cambridge CB2 0SP, England. EM ay276@cam.ac.uk NR 39 TC 0 Z9 0 U1 1 U2 3 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 2296-2360 J9 FRONT PEDIATR JI Front. Pediatr. PY 2013 VL 1 AR 7 DI 10.3389/fped.2013.00007 PG 7 WC Pediatrics SC Pediatrics GA V46PH UT WOS:000209895600007 PM 24400253 ER PT J AU Le, KA Li, Y Xu, XJ Yang, WT Liu, TT Zhao, XN Tang, YG Cai, DH Go, VLW Pandol, S Hui, HX AF Le, Kim-Anne Li, Yan Xu, Xiaojing Yang, Wanting Liu, Tingting Zhao, Xiaoning Tang, Yongming Gorge Cai, Dehong Go, Vay Liang W. Pandol, Stephen Hui, Hongxiang TI Alterations in fecal Lactobacillus and Bifidobacterium species in type 2 diabetic patients in Southern China population SO FRONTIERS IN PHYSIOLOGY LA English DT Article DE microbiota; microflora; metabolic diseases; gut ID DIET-INDUCED OBESITY; GUT MICROBIOTA; INSULIN-RESISTANCE; MICE; INFLAMMATION; ENDOTOXEMIA AB Background: The connection between gut microbiota and metabolism and its role in the pathogenesis of diabetes are increasingly recognized. The objective of this study was to quantitatively measure Bifidobacterium and Lactobacillus species, members of commensal bacteria found in human gut, in type 2 diabetic patients (T2D) patients from Southern China. Methods: Fifty patients with T2D and thirty control individuals of similar body mass index (BMI) were recruited from Southern China. T2D and control subjects were confirmed with both oral glucose tolerance test (OGTT) and HbA(1c), measurements. Bifidobacterium and Lactobacillus species in feces were measured by real-time quantitative PCR. Data were analyzed with STATA 11.0 statistical software. Results: In comparison to control subjects T2D patients had significantly more total Lactobacillus (+18%), L. bugaricus (+13%), L. rhamnosum (+37%) and L. acidophilus (+48%) (P < 0.05). In contrast, T2D patients had less amounts of total Bifidobacteria (-7%) and B. adolescentis (-12%) (P < 0.05). Cluster analysis showed that gut microbiota pattern of T2D patients is characterized by greater numbers of L. rharmosus and L. acidophillus, together with lesser numbers of B. adolescentis (P < 0.05). Conclusion: The gut microflora in T2D patients is characterized by greater numbers of Lactobacillus and lesser numbers of Bifidobacterium species. C1 [Le, Kim-Anne; Li, Yan; Yang, Wanting; Zhao, Xiaoning; Tang, Yongming Gorge; Cai, Dehong; Go, Vay Liang W.; Pandol, Stephen; Hui, Hongxiang] Southern Med Univ, Int Ctr Metab Dis, Guangzhou 510515, Guangdong, Peoples R China. [Le, Kim-Anne] Nestec Ltd, Nestle Res Ctr, Nutr & Hlth Dept, Lausanne, Switzerland. [Li, Yan; Yang, Wanting; Zhao, Xiaoning; Hui, Hongxiang] Dongguan SMU Metab Med Inc Ltd, Dongguang, Peoples R China. [Li, Yan; Hui, Hongxiang] Southern Med Univ, Sch Biotechnol, Guangzhou 510515, Guangdong, Peoples R China. [Xu, Xiaojing; Liu, Tingting; Cai, Dehong; Hui, Hongxiang] Southern Med Univ, Zhujiang Hosp, Dept Endocrinol, Guangzhou 510515, Guangdong, Peoples R China. [Zhao, Xiaoning; Cai, Dehong; Hui, Hongxiang] Southern Med Univ, Beijiao Hosp, Ctr Metab Dis, Guangzhou 510515, Guangdong, Peoples R China. [Zhao, Xiaoning; Tang, Yongming Gorge; Pandol, Stephen] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. [Go, Vay Liang W.; Pandol, Stephen; Hui, Hongxiang] VA Greater Los Angeles Hlth Care Syst, Dept Med, Los Angeles, CA USA. [Go, Vay Liang W.; Pandol, Stephen; Hui, Hongxiang] Univ Calif Los Angeles, David Geffen Sch Med, UCLA Ctr Excellence Pancreat Dis, Los Angeles, CA 90095 USA. RP Hui, HX (reprint author), Southern Med Univ, Int Ctr Metab Dis, 8 Floor,Life Sci Build,North 1838 Guangzhou Rd, Guangzhou 510515, Guangdong, Peoples R China. EM huihongx@gmail.com FU Major State Basic Research Development Program of China 973 Program [2011CB504006]; Songshan Lake Sci. & Tech. Industry Park Fund [2010B025, 2010B026]; Ph.D. Programs Foundation of Ministry of Education of China [20104433110014]; Guangdong science and Technology Research Fund [2010B090400041]; Guangdong Department of Education Fund; United State Department of Veterans Affairs; Hirshberg Foundation FX This research was partially supported by the Major State Basic Research Development Program of China 973 Program (No. 2011CB504006), Songshan Lake Sci. & Tech. Industry Park Fund (No. 2010B025 & No. 2010B026), Ph.D. Programs Foundation of Ministry of Education of China (No. 20104433110014), Guangdong science and Technology Research Fund (No. 2010B090400041) and Guangdong Department of Education Fund. The United State Department of Veterans Affairs and Hirshberg Foundation. NR 20 TC 2 Z9 2 U1 1 U2 7 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-042X J9 FRONT PHYSIOL JI Front. Physiol. PY 2013 VL 3 AR UNSP 496 DI 10.3389/fphys.2012.00496 PG 6 WC Physiology SC Physiology GA AX2KX UT WOS:000346773600020 ER PT J AU Panichello, MF Cheung, OS Bar, M AF Panichello, Matthew F. Cheung, Olivia S. Bar, Moshe TI Predictive feedback and conscious visual experience SO FRONTIERS IN PSYCHOLOGY LA English DT Review DE predictions; context; object recognition; priming; visual awareness; top-down; perception; associative processing AB The human brain continuously generates predictions about the environment based on learned regularities in the world. These predictions actively and efficiently facilitate the interpretation of incoming sensory information. We review evidence that, as a result of this facilitation, predictions directly influence conscious experience. Specifically, we propose that predictions enable rapid generation of conscious percepts and bias the contents of awareness in situations of uncertainty. The possible neural mechanisms underlying this facilitation are discussed. C1 [Panichello, Matthew F.; Cheung, Olivia S.; Bar, Moshe] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Panichello, Matthew F.; Cheung, Olivia S.; Bar, Moshe] Harvard Univ, Sch Med, Charlestown, MA USA. [Bar, Moshe] Bar Ilan Univ, Gonda Multidisciplinary Brain Res Ctr, Ramat Gan, Israel. RP Panichello, MF (reprint author), Martinos Ctr Biomed Imaging, 149 Thirteenth St,Suite 2301, Charlestown, MA 02129 USA. EM panichem@nmr.mgh.harvard.edu FU NSF [BCS-0842947]; DARPA [N10AP20036] FX This work was supported by NSF grant BCS-0842947 and DARPA grant N10AP20036. NR 109 TC 21 Z9 23 U1 2 U2 4 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-1078 J9 FRONT PSYCHOL JI Front. Psychol. PY 2013 VL 3 AR 620 DI 10.3389/fpsyg.2012.00620 PG 8 WC Psychology, Multidisciplinary SC Psychology GA V43MB UT WOS:000209684400035 PM 23346068 ER PT B AU Golberg, A Linshiz, G Koudritsky, M Chemodanov, A Hillson, NJ AF Golberg, A. Linshiz, G. Koudritsky, M. Chemodanov, A. Hillson, N. J. GP ASME TI DISTRIBUTED MARINE BIOREFINERIES FOR DEVELOPING ECONOMIES SO INTERNATIONAL MECHANICAL ENGINEERING CONGRESS AND EXPOSITION - 2012, VOL 6, PTS A AND B LA English DT Proceedings Paper CT ASME International Mechanical Engineering Congress and Exposition CY NOV 09-15, 2012 CL Houston, TX SP ASME ID MICROBIAL-PRODUCTION; CONSTRUCTAL DESIGN; BIOMASS YIELD; SEAWEED; BIOENERGY; BIOFUELS; CULTIVATION; PLANT; POWER AB In the coming decades, developing countries will be responsible for significant increases in liquid fuel demand. There is an urgent need to develop alternative, preferably carbon-neutral, transportation fuels to supplement limited fossil fuel resources and minimize undesirable climatic change. While biofuels present a promising alternative to fossil fuels, sustainable biorefinery process design remains challenging. Efficiencies of scale realized by large centralized facilities are offset by increased feedstock collection and fuel distribution logistical costs. In this work, we use a thermodynamic balance approach to derive the optimal serviced territory size for a single biorefinery. We find that the optimal size decreases with increasing population density and per capita fuel consumption. We propose a modular, scalable, and sustainable biorefinery design based on the marine macro algae Ulva sp. To demonstrate the design principal, we provide an example marine biorefinery design for a coastal town of 20,000 inhabitants in rural India. Beyond basic biorefinery design, we consider biorefinery integration into distributed power sources and environmental impacts. C1 [Golberg, A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. [Golberg, A.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Golberg, A.] Univ Calif Berkeley, Dept Mech Engn, Berkeley, CA USA. [Linshiz, G.; Hillson, N. J.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Joint BioEnergy Inst, Berkeley, CA 94720 USA. RP Golberg, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. EM agolberg@gmail.com; gregory.linshiz@gmail.com; kamrik@gmail.com; alex.che.57@gmail.com; njhillson@lbl.gov NR 44 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-4522-6 PY 2013 BP 493 EP 501 PG 9 WC Energy & Fuels; Engineering, Mechanical SC Energy & Fuels; Engineering GA BC1GD UT WOS:000350070400056 ER PT J AU Garg, S Deschler, D AF Garg, Shweta Deschler, Daniel TI Saving a free flap with close clinical postoperative monitoring SO JAAPA-JOURNAL OF THE AMERICAN ACADEMY OF PHYSICIAN ASSISTANTS LA English DT Article C1 [Garg, Shweta; Deschler, Daniel] Massachusetts Eye & Ear Infirm, Head & Neck Surg Oncol, Boston, MA 02114 USA. [Deschler, Daniel] Harvard Univ, Sch Med, Boston, MA USA. RP Garg, S (reprint author), Massachusetts Eye & Ear Infirm, Head & Neck Surg Oncol, Boston, MA 02114 USA. NR 9 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 1547-1896 EI 0893-7400 J9 JAAPA-J AM ACAD PHYS JI JAAPA-J. Am. Acad. Physician Assist. PD JAN PY 2013 VL 26 IS 1 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA V39OX UT WOS:000209421400010 ER PT J AU Connelly, K Nguyen, T AF Connelly, Kelly Nguyen, Timothy TI Human Immunodeficiency Virus-Associated Nephropathy: A Case Assessment SO JNP-JOURNAL FOR NURSE PRACTITIONERS LA English DT Article DE chronic kidney disease; end stage renal disease; highly active antiretroviral therapy; human immunodeficiency virus-associated nephropathy AB Kidney disease and highly active antiretroviral therapy (HAART) are associated with and have important roles in the management of human immunodeficiency virus-associated nephropathy (HIVAN). HIVAN can progress to deadly end-stage kidney disease. Current recommendations for HIVAN treatments are largely based on observational data and uncontrolled trials. Potential beneficial treatments include HAART, angiotensin-converting enzyme inhibitors, corticosteroid, dialysis, and renal transplant. Nurse practitioners play important roles in caring for patients with HIVAN. C1 [Connelly, Kelly] Mt Sinai Med Ctr, Brooklyn, NY 11234 USA. [Nguyen, Timothy] Long Isl Univ, Coll Pharm & Hlth Sci, Pharm Practice, Brooklyn, NY 11548 USA. [Nguyen, Timothy] Mt Sinai Kidney Ctr, Nephrol & Dialysis, New York, NY USA. RP Connelly, K (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM klconnelly@partners.org NR 28 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 1555-4155 EI 1878-058X J9 JNP-J NURSE PRACT JI JNP-J. Nurse Pract. PD JAN PY 2013 VL 9 IS 1 BP 40 EP 45 DI 10.1016/j.nurpra.2012.11.008 PG 6 WC Nursing SC Nursing GA V39HS UT WOS:000209402700011 ER PT J AU Bankova, LG Walter, JE Iyengar, SR Lorenzo, ME Hornick, JL Castells, MC AF Bankova, Lora G. Walter, Jolan E. Iyengar, Shuba R. Lorenzo, Mayra E. Hornick, Jason L. Castells, Mariana C. TI Generalized Bullous Eruption after Routine Vaccination in a Child with Diffuse Cutaneous Mastocytosis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE LA English DT Editorial Material C1 [Bankova, Lora G.; Castells, Mariana C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Cambridge, MA 02138 USA. [Walter, Jolan E.; Iyengar, Shuba R.] Harvard Univ, Sch Med, MassGen Hosp Children, Div Allergy Immunol & Pulmonol, Cambridge, MA 02138 USA. [Lorenzo, Mayra E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Cambridge, MA 02138 USA. [Hornick, Jason L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Cambridge, MA 02138 USA. RP Castells, MC (reprint author), One Jimmy Fund Way,Smith Bldg,Rm 626 D, Boston, MA 02115 USA. EM mcastells@partners.org NR 9 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2198 EI 2213-2201 J9 J ALLER CL IMM-PRACT JI J. Allergy Clin. Immunol.-Pract. PD JAN PY 2013 VL 1 IS 1 BP 94 EP 96 DI 10.1016/j.jaip.2012.08.008 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA V38WT UT WOS:000209374200014 PM 24229828 ER PT J AU Cugini, C Klepac-Ceraj, V Rackaityte, E Riggs, JE Davey, ME AF Cugini, Carla Klepac-Ceraj, Vanja Rackaityte, Elze Riggs, James E. Davey, Mary E. TI Porphyromonas gingivalis: keeping the pathos out of the biont SO JOURNAL OF ORAL MICROBIOLOGY LA English DT Review DE pathobiont; P. gingivalis; biofilm; tumor; immunoediting hypothesis AB The primary goal of the human microbiome initiative has been to increase our understanding of the structure and function of our indigenous microbiota and their effects on human health and predisposition to disease. Because of its clinical importance and accessibility for in vivo study, the oral biofilm is one of the best-understood microbial communities associated with the human body. Studies have shown that there is a succession of select microbial interactions that directs the maturation of a defined community structure, generating the formation of dental plaque. Although the initiating factors that lead to disease development are not clearly defined, in many individuals there is a fundamental shift from a health-associated biofilm community to one that is pathogenic in nature and a central player in the pathogenic potential of this community is the presence of Porphyromonas gingivalis. This anaerobic bacterium is a natural member of the oral microbiome, yet it can become highly destructive (termed pathobiont) and proliferate to high cell numbers in periodontal lesions, which is attributed to its arsenal of specialized virulence factors. Hence, this organism is regarded as a primary etiologic agent of periodontal disease progression. In this review, we summarize some of the latest information regarding what is known about its role in periodontitis, including pathogenic potential as well as ecological and nutritional parameters that may shift this commensal to a virulent state. We also discuss parallels between the development of pathogenic biofilms and the human cellular communities that lead to cancer, specifically we frame our viewpoint in the context of 'wounds that fail to heal'. C1 [Cugini, Carla; Klepac-Ceraj, Vanja] Forsyth Inst, Dept Microbiol, Cambridge, MA USA. [Cugini, Carla] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Klepac-Ceraj, Vanja; Rackaityte, Elze] Wellesley Coll, Dept Biol Sci, Wellesley, MA 02181 USA. [Riggs, James E.] Rider Univ, Dept Biol, Lawrenceville, NJ 08648 USA. [Davey, Mary E.] Univ Florida, Coll Dent, Dept Oral Biol, Gainesville, FL 32610 USA. RP Davey, ME (reprint author), Univ Florida, Coll Dent, Dept Oral Biol, 1395 Ctr Dr, Gainesville, FL 32610 USA. EM riggs@rider.edu; mdavey@dental.ufl.edu OI Klepac-Ceraj, Vanja/0000-0001-5387-5706 FU Rider University; National Institute of Health, Academic Research Enhancement Award program [R15 AI CA 136901-01]; National Institute of Dental and Craniofacial Research [DE-019117] FX We would like to thank all of the members of the 'Dynamics of Host-Associated Microbial Communities' focus group at Forsyth for all of the thought-provoking questions and stimulating discussions that led to the writing of this review article. J. Riggs was supported by a research leave provided by Rider University and a grant from the National Institute of Health, Academic Research Enhancement Award (R15 AI CA 136901-01) program. M.E. Davey was supported by grant DE-019117 from National Institute of Dental and Craniofacial Research. NR 129 TC 7 Z9 7 U1 2 U2 5 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2000-2297 J9 J ORAL MICROBIOL JI J. Oral Microbiology PY 2013 VL 5 AR 19804 DI 10.3402/jom.v5i0.19804 PG 10 WC Microbiology SC Microbiology GA V41HF UT WOS:000209536600002 ER PT J AU Mdala, I Olsen, I Haffajee, AD Socransky, SS de Blasio, BF Thoresen, M AF Mdala, Ibrahimu Olsen, Ingar Haffajee, Anne D. Socransky, Sigmund S. de Blasio, Birgitte Freiesleben Thoresen, Magne TI Multilevel analysis of bacterial counts from chronic periodontitis after root planing/scaling, surgery, and systemic and local antibiotics: 2-year results SO JOURNAL OF ORAL MICROBIOLOGY LA English DT Article DE microbiota; chronic periodontitis; periodontal therapy; antibiotics; multilevel analysis; NB GEE; fractional response methods AB Aim: To follow changes (over 2 years) in subgingival bacterial counts of five microbial complexes including health-related Actinomyces spp. in deeper pockets (>= 5 mm) after periodontal treatments. Methods: Eight different treatments were studied: (1) scaling + root planing (SRP); (2) periodontal surgery (SURG) + systemic amoxicillin (AMOX) + systemic metronidazole (MET); (3) SURG + locally delivered tetracycline (TET); (4) SURG; (5) AMOX + MET + TET; (6) AMOX + MET; (7) TET; and (8) SURG + AMOX + MET + TET. Antibiotics were given immediately following SRP. Subgingival plaque was collected mesiobuccally from each tooth, except third molars, from 176 subjects, completing the study, at baseline, 3, 6, 12, 18, and 24 months post-treatment and analysed for 40 different bacteria using checkerboard hybridization. A negative binomial (NB) generalized estimating equation (NB GEE) model was used to analyze count data and a logistic GEE was used for proportions. Results: We observed short-term beneficial changes in the composition of the red complex of up to 3 months by treating subjects with AMOX + MET + TET. Similar short-term improvements with the same treatment were observed for Tannerella forsythia and Treponema denticola of the red complex. SURG had also short-term beneficial effect on Porphyromonas gingivalis. No periodontal treatments applied to severely affected sites promoted the growth of Actinomyces. Smoking elevated counts of both the red and orange complex while bleeding on probing (BOP) and gingival redness were also predictors of more red complex counts. Comparatively similar findings were obtained by analyzing counts and by analyzing proportions. Conclusions: Although short-term reductions in the counts of the red complex were observed in sites that were treated with AMOX + MET + TET, long-term significant effects were not observed with any of the eight treatments. Poor oral hygiene in patients with severe chronic periodontitis diminished the beneficial effects of treatment. C1 [Mdala, Ibrahimu; Olsen, Ingar] Univ Oslo, Dept Oral Biol, Fac Dent, NO-0316 Oslo, Norway. [Haffajee, Anne D.; Socransky, Sigmund S.] Forsyth Inst, Dept Periodontol, Cambridge, MA USA. [de Blasio, Birgitte Freiesleben; Thoresen, Magne] Univ Oslo, Inst Basic Med Sci, Dept Biostat, Oslo, Norway. [de Blasio, Birgitte Freiesleben] Norwegian Inst Publ Hlth, Div Infect Dis Surveillance, Dept Infect Dis Epidemiol, Oslo, Norway. RP Mdala, I (reprint author), Univ Oslo, Dept Oral Biol, Fac Dent, PB 1052, NO-0316 Oslo, Norway. EM ibrahimu.mdala@odont.uio.no FU Faculty of Dentistry, University of Oslo, Norway; National Institute of Dental and Craniofacial Research [DE 12861]; European Commission [FP7-HEALTH-306029] FX There is no conflict of interest for any of the authors. Funding was from the Faculty of Dentistry, University of Oslo, Norway, from the National Institute of Dental and Craniofacial Research (grant DE 12861) and grant from the European Commission [FP7-HEALTH-306029 "TRIGGER"]. NR 35 TC 3 Z9 3 U1 0 U2 0 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2000-2297 J9 J ORAL MICROBIOL JI J. Oral Microbiology PY 2013 VL 5 AR 20939 DI 10.3402/jom.v5i0.20939 PG 14 WC Microbiology SC Microbiology GA V41HF UT WOS:000209536600009 ER PT J AU Chaudhry, ZA Najib, U Bajwa, ZH Jacobs, WC Sheikh, J Simopoulos, TT AF Chaudhry, Zeshan Ahmed Najib, Umer Bajwa, Zahid H. Jacobs, W. Carl Sheikh, Javed Simopoulos, Thomas T. TI Detailed analysis of allergic cutaneous reactions to spinal cord stimulator devices SO JOURNAL OF PAIN RESEARCH LA English DT Article DE spinal cord stimulation; delayed inflammatory responses; foreign body giant cell reactions; contact dermatitis AB The use of spinal cord stimulation (SCS) devices to treat chronic, refractory neuropathic pain continues to expand in application. While device-related complications have been well described, inflammatory reactions to the components of these devices remain underreported. In contrast, hypersensitivity reactions associated with other implanted therapies, such as endovascular and cardiac rhythm devices, have been detailed. The purpose of this case series is to describe the clinical presentation and course of inflammatory reactions as well as the histology of these reactions. All patients required removal of the entire device after developing inflammatory reactions over a time course of 1-3 months. Two patients developed a foreign body reaction in the lead insertion wound as well as at the implantable pulse generator site, with histology positive for giant cells. One patient developed an inflammatory dermatitis on the flank and abdomen that resolved with topical hydrocortisone. "In vivo" testing with a lead extension fragment placed in the buttock resulted in a negative reaction followed by successful reimplantation of an SCS device. Inflammatory reactions to SCS devices can manifest as contact dermatitis, granuloma formation, or foreign body reactions with giant cell formation. Tissue diagnosis is essential, and is helpful to differentiate an inflammatory reaction from infection. The role of skin patch testing for 96 hours may not be suited to detect inflammatory giant cell reactions that manifest several weeks post implantation. C1 [Chaudhry, Zeshan Ahmed] Harvard Univ, Massachusetts Gen Hosp, Dept Diagnost & Intervent Neuroradiol, Sch Med, Boston, MA 02215 USA. [Najib, Umer] W Virginia Univ, Dept Neurol, Robert C Byrd Hlth Sci Ctr, Morgantown, WV 26506 USA. [Bajwa, Zahid H.] Boston Headache Inst, Waltham, MA USA. [Jacobs, W. Carl] Harvard Univ, Dept Pathol, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Sheikh, Javed] Beth Israel Deaconess Med Ctr, Dept Med Allergy & Immunol, Brookline, MA USA. [Simopoulos, Thomas T.] Beth Israel Deaconess Med Ctr, Dept Anesthesia, Brookline, MA USA. RP Simopoulos, TT (reprint author), Harvard Univ, Dept Anesthesia, Beth Israel Deaconess Med Ctr, Sch Med, 330 Brookline Ave, Boston, MA 02215 USA. EM tsimopou@bidmc.harvard.edu NR 13 TC 1 Z9 1 U1 0 U2 0 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-7090 J9 J PAIN RES JI J. Pain Res. PY 2013 VL 6 BP 617 EP 623 DI 10.2147/JPR.S44676 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA V41EG UT WOS:000209528900066 PM 23946668 ER PT J AU Belkind-Gerson, J Goldstein, AM Kuo, B AF Belkind-Gerson, Jaime Goldstein, Allan M. Kuo, Braden TI Balloon Expulsion Test as a Screen for Outlet Obstruction in Children With Chronic Constipation SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE anorectal manometry; balloon expulsion; children; constipation; defecation disorders ID CHILDHOOD CONSTIPATION; FOLLOW-UP; DIAGNOSIS; MANOMETRY; CARE AB Objective: Chronic constipation (CC) is a common problem in pediatrics and is often the result of obstructed defecation. The aim of the present study was to study the feasibility and efficacy of the balloon expulsion test (BET) in the diagnosis and management of children with CC. Methods: Retrospective study comparing BET and high-resolution anorectal manometry (ARM). The BET was done together with ARM in 29 children, ages 8 to 19 years, with CC. For BET, a 60-mL balloon was used. Passage of balloon in 1 minute or less was considered normal. Results: Fifteen of the 29 children had a normal BET. Of these, 14 also had an ARM, all of which were normal (except for 2 cases with a hypertonic baseline anal sphincter). Thus 12 of 14 with BET and ARM were normal on both (correlation between the tests 86%). Of the 14 children that failed BET, 10 had distal abnormalities by ARM, contrast studies, EMG, or assessment by a pelvic physical therapist. All of the patients with a nonrelaxing sphincter or outlet obstruction were treated with laxatives, anal sphicter Botox, and/or pelvic physical therapy and biofeedback. In follow-up of at least 3 months, all of the patients with a failed BET were improved. Conclusions: We found a high correlation between a normal ARM and BET. If the BET is abnormal and the ARM does not identify a cause for the distal obstruction, additional studies may be needed, including contrast enema, defecography, or electromyography. BET appears to be a safe, reliable, and useful test in the evaluation and management of CC in children. C1 [Belkind-Gerson, Jaime; Kuo, Braden] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP Belkind-Gerson, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. EM jbelkindgerson@partners.org NR 16 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-2116 EI 1536-4801 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD JAN PY 2013 VL 56 IS 1 BP 23 EP 26 DI 10.1097/MPG.0b013e31826a909f PG 4 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 063UV UT WOS:000313028400012 PM 22847462 ER PT J AU Chao, W Kolski-Andreaco, A AF Chao, Wendy Kolski-Andreaco, Aaron TI 2012: A Year In Review SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE This Month in JoVE; Issue 71 AB Here's a look at some of the milestones and highlights of the year 2012 in Journal of Visualized Experiments (JoVE). At the start of 2012, JoVE reached a major milestone by publishing our 1500th article. In this publication, in JoVE Bioengineering, Yu et al. described a method for analyzing the free radical composition of cigarette smoke. This method simulated cigarette puffing with a single-port smoking device, and combined it with electron spin resonance (ESR) spectroscopy to measure the degree to which antioxidant compounds can scavenge free radicals in cigarette smoke. A possible outcome of this research is the creation of less harmful cigarettes. JoVE Bioengineering also contained the most-viewed article of 2012. Owczarczak et al. described a method for hacking a standard inkjet printer, loading ink cartridges with a cell-suspension "bioink," and printing lines of live cells onto glass slides. The thermal inkjet printing process creates temporary pores in the cell membrane, visualized by the incorporation of fluorescently labeled actin monomers. This concept, called "bioprinting," has many potential applications in cell and tissue engineering. Also in 2012, JoVE Bioengineering featured a protocol by Hsia et al. for isolating and purifying spider silk protein, spinning it into fibers, and assessing the fiber strength. This protocol for laboratory-scale production of spider silk, which is stronger than tensile steel, can potentially be extended to large-scale manufacturing. In JoVE Clinical and Translational Medicine, we featured a number of articles related to stroke, one of which. In one article, Mobius-Winkler et al. demonstrated placement of the WATCHMAN left atrial appendage occlusion device from Boston Scientific. This device is designed to prevent strokes by trapping clots within the left atrial appendage of the heart before they exit. Our authors demonstrated how to insert the guide wire through the femoral artery into the heart, advance the device into the left atrium, and deploy the device in the left atrial appendage. Another article focused on stroke, Hamel et al. described the use of a driving simulator to study how patients compensate for visual field defects following stroke. By analyzing the compensatory gaze behavior of patients as they navigated through virtual driving courses with varying degrees of complexity, our authors see great potential for the use of driving simulators in stroke rehabilitation. In JoVE Immunology and Infection, we published an article by Keyel et al. describing the real-time kinetics of immune cell responses to bacterial toxins using live cell microscopy. Combined with high-speed 3D confocal microscopy, this technique can also visualize the cellular repair response. Also in JoVE Immunology and Infection, we featured an article by Yap et al. describing methods for diagnosing helminth infections in children. Helminths are parasitic worms that can infect the intestinal tract of humans and animals, and may be distinguished based on their morphology. The same article demonstrated how to measure the impact of helminth infections on physical fitness in children, which is a measure of overall health. In JoVE Neuroscience, we featured a method by Hoffmann et al., who used tiny headphones to alter the auditory feedback in songbirds, and analyzed the computational and neurophysiological basis of vocal learning in birds when they adjust their singing in response to altered acoustic signals. Also in JoVE Neuroscience, we moved from birds to bees with a method that assesses associative and non-associative tactile learning in honeybees. This method, by Mujagic et al., allowed bees to scan different metal surfaces with their antennae, then conditioned them to expect sugar water when their antennae touched particular surfaces, and analyzed the corresponding changes in antennal movement. In 2012, we launched a brand-new section: JoVE Applied Physics, which features articles on subjects ranging from plasma physics to material science. The Applied Physics section also contained JoVE's 2000th video article, filmed in a synchrotron radiation facility, where Borisenko et al. showed how to determine the electronic structure of complex materials using angle-resolved photoemission spectroscopy. In the JoVE General section, we published an article by Artioli et al. demonstrating the use of a portable gas analyzer to measure oxygen consumption during complex exercise - such as judo. By analyzing oxygen consumption and collecting blood for measuring plasma lactate concentration, this method can determine the relative contributions of different energy systems to specific aspects of complex exercise. Finally, JoVE followed Dolhi et al. to a permanently ice-covered saline lake in Antarctica. There, scientists drilled through the ice to study single-celled microorganisms called protists that live in the harsh conditions of Antarctica. This Year in Review was just a brief glimpse of a few of over 600 video articles that JoVE offered in 2012. Browse the JoVE archives to see thousands of other videos, and stay tuned for what's coming up this year in JoVE: The Journal of Visualized Experiments. C1 [Chao, Wendy] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Kolski-Andreaco, A (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. EM aaron.kolski-andreaco@jove.com NR 0 TC 0 Z9 0 U1 1 U2 21 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 JAN PY 2013 IS 71 AR UNSP e5049 DI 10.3791/5049 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V36QO UT WOS:000209226200054 ER PT J AU Hariri, LP Applegate, MB Mino-Kenudson, M Mark, EJ Bouma, BE Tearney, GJ Suter, MJ AF Hariri, Lida P. Applegate, Matthew B. Mino-Kenudson, Mari Mark, Eugene J. Bouma, Brett E. Tearney, Guillermo J. Suter, Melissa J. TI Optical Frequency Domain Imaging of Ex vivo Pulmonary Resection Specimens: Obtaining One to One Image to Histopathology Correlation SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Bioengineering; Issue 71; Medicine; Biomedical Engineering; Anatomy; Physiology; Cancer Biology; Pathology; Surgery; Bronchoscopic imaging; In vivo optical microscopy; Optical imaging; Optical coherence tomography; Optical frequency domain imaging; Histology correlation; animal model; histopathology; airway; lung; biopsy; imaging AB Lung cancer is the leading cause of cancer-related deaths(1). Squamous cell and small cell cancers typically arise in association with the conducting airways, whereas adenocarcinomas are typically more peripheral in location. Lung malignancy detection early in the disease process may be difficult due to several limitations: radiological resolution, bronchoscopic limitations in evaluating tissue underlying the airway mucosa and identifying early pathologic changes, and small sample size and/or incomplete sampling in histology biopsies. High resolution imaging modalities, such as optical frequency domain imaging (OFDI), provide non-destructive, large area 3-dimensional views of tissue microstructure to depths approaching 2 mm in real time (Figure 1) (2-6). OFDI has been utilized in a variety of applications, including evaluation of coronary artery atherosclerosis(6,7) and esophageal intestinal metaplasia and dysplasia(6,8-10). Bronchoscopic OCT/OFDI has been demonstrated as a safe in vivo imaging tool for evaluating the pulmonary airways (11-23) (Animation). OCT has been assessed in pulmonary airways (16,23) and parenchyma(17,22) of animal models and in vivo human airway(14,15). OCT imaging of normal airway has demonstrated visualization of airway layering and alveolar attachments, and evaluation of dysplastic lesions has been found useful in distinguishing grades of dysplasia in the bronchial mucosa (11,12,20,21). OFDI imaging of bronchial mucosa has been demonstrated in a short bronchial segment (0.8 cm) (18). Additionally, volumetric OFDI spanning multiple airway generations in swine and human pulmonary airways in vivo has been described(19). Endobronchial OCT/OFDI is typically performed using thin, flexible catheters, which are compatible with standard bronchoscopic access ports. Additionally, OCT and OFDI needle-based probes have recently been developed, which may be used to image regions of the lung beyond the airway wall or pleural surface(17). While OCT/OFDI has been utilized and demonstrated as feasible for in vivo pulmonary imaging, no studies with precisely matched one-to-one OFDI:histology have been performed. Therefore, specific imaging criteria for various pulmonary pathologies have yet to be developed. Histopathological counterparts obtained in vivo consist of only small biopsy fragments, which are difficult to correlate with large OFDI datasets. Additionally, they do not provide the comprehensive histology needed for registration with large volume OFDI. As a result, specific imaging features of pulmonary pathology cannot be developed in the in vivo setting. Precisely matched, one-to-one OFDI and histology correlation is vital to accurately evaluate features seen in OFDI against histology as a gold standard in order to derive specific image interpretation criteria for pulmonary neoplasms and other pulmonary pathologies. Once specific imaging criteria have been developed and validated ex vivo with matched one-to-one histology, the criteria may then be applied to in vivo imaging studies. Here, we present a method for precise, one to one correlation between high resolution optical imaging and histology in ex vivo lung resection specimens. Throughout this manuscript, we describe the techniques used to match OFDI images to histology. However, this method is not specific to OFDI and can be used to obtain histology-registered images for any optical imaging technique. We performed airway centered OFDI with a specialized custom built bronchoscopic 2.4 French (0.8 mm diameter) catheter. Tissue samples were marked with tissue dye, visible in both OFDI and histology. Careful orientation procedures were used to precisely correlate imaging and histological sampling locations. The techniques outlined in this manuscript were used to conduct the first demonstration of volumetric OFDI with precise correlation to tissue-based diagnosis for evaluating pulmonary pathology(24). This straightforward, effective technique may be extended to other tissue types to provide precise imaging to histology correlation needed to determine fine imaging features of both normal and diseased tissues. C1 [Hariri, Lida P.; Mino-Kenudson, Mari; Mark, Eugene J.; Tearney, Guillermo J.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. [Hariri, Lida P.; Mino-Kenudson, Mari; Mark, Eugene J.; Bouma, Brett E.; Tearney, Guillermo J.; Suter, Melissa J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hariri, Lida P.; Bouma, Brett E.; Tearney, Guillermo J.; Suter, Melissa J.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Cambridge, MA 02138 USA. [Applegate, Matthew B.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Suter, Melissa J.] Harvard Univ, Sch Med, Pulm & Crit Care Unit, Cambridge, MA 02138 USA. RP Suter, MJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM msuter@partners.org FU National Institute of Heath [R00CA134920]; American Lung Association [RG-194681-N]; NinePoint Medical Inc. FX The authors would like to thank Mr. Sven Holder and Mr. Stephen Conley for their invaluable assistance in this study. This work was funded in part by the National Institute of Heath [Grant number R00CA134920] and the American Lung Association [Grant number RG-194681-N]. NinePoint Medical Inc. sponsored the publication costs associated with this manuscript. NR 30 TC 1 Z9 1 U1 0 U2 3 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 JAN PY 2013 IS 71 AR UNSP e3855 DI 10.3791/3855 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V36QO UT WOS:000209226200004 ER PT B AU Ross, EV Anderson, RR AF Ross, E. Victor Anderson, R. Rox BE Goldman, MP Fitzpatrick, RE Ross, EV Kilmer, SL Weiss, RA TI Laser-tissue interactions SO LASERS AND ENERGY DEVICES FOR THE SKIN, 2ND EDITION LA English DT Article; Book Chapter ID PULSED DYE-LASER; SWITCHED RUBY-LASER; PORT-WINE STAINS; ND-YAG LASER; 308-NM EXCIMER-LASER; NM DIODE-LASER; PHOTODYNAMIC THERAPY; HAIR REMOVAL; SELECTIVE PHOTOTHERMOLYSIS; ACNE SCARS C1 [Ross, E. Victor] Scripps Clin, Laser & Cosmet Dermatol Ctr, San Diego, CA 92037 USA. [Anderson, R. Rox] Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Ross, EV (reprint author), Scripps Clin, Laser & Cosmet Dermatol Ctr, San Diego, CA 92037 USA. NR 157 TC 1 Z9 1 U1 2 U2 2 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-84184-934-8; 978-1-84184-933-1 PY 2013 BP 1 EP 30 PG 30 WC Dermatology; Physics, Applied SC Dermatology; Physics GA BD4WN UT WOS:000361147900001 ER PT B AU Ibrahimi, OA Kilmer, SL AF Ibrahimi, Omar A. Kilmer, Suzanne L. BE Goldman, MP Fitzpatrick, RE Ross, EV Kilmer, SL Weiss, RA TI Laser treatment of benign pigmented lesions SO LASERS AND ENERGY DEVICES FOR THE SKIN, 2ND EDITION LA English DT Article; Book Chapter ID SWITCHED RUBY-LASER; ND-YAG LASER; DERMATOSIS PAPULOSA NIGRA; ALUMINUM-GARNET LASER; TERM-FOLLOW-UP; FRACTIONAL PHOTOTHERMOLYSIS; ALEXANDRITE LASER; SELECTIVE PHOTOTHERMOLYSIS; NEVUS-SPILUS; REFRACTORY MELASMA C1 [Ibrahimi, Omar A.] Connecticut Skin Inst, Stamford, CT 06905 USA. [Ibrahimi, Omar A.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Ibrahimi, Omar A.] Harvard Univ, Sch Med, Boston, MA USA. [Kilmer, Suzanne L.] Laser & Skin Surg Ctr Northern Calif, Sacramento, CA USA. RP Ibrahimi, OA (reprint author), Connecticut Skin Inst, Stamford, CT 06905 USA. NR 69 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-84184-934-8; 978-1-84184-933-1 PY 2013 BP 58 EP 73 PG 16 WC Dermatology; Physics, Applied SC Dermatology; Physics GA BD4WN UT WOS:000361147900003 ER PT B AU Ibrahimi, OA Kilmer, SL AF Ibrahimi, Omar A. Kilmer, Suzanne L. BE Goldman, MP Fitzpatrick, RE Ross, EV Kilmer, SL Weiss, RA TI Hair removal SO LASERS AND ENERGY DEVICES FOR THE SKIN, 2ND EDITION LA English DT Article; Book Chapter ID INTENSE PULSED-LIGHT; MODE RUBY-LASER; DIODE-LASER; ISOTRETINOIN THERAPY; ALEXANDRITE LASER; FOLLOW-UP; ND-YAG; SELECTIVE PHOTOTHERMOLYSIS; RANDOMIZED-TRIAL; PHOTO-EPILATION C1 [Ibrahimi, Omar A.] Connecticut Skin Inst, Stamford, CT 06905 USA. [Ibrahimi, Omar A.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Ibrahimi, Omar A.] Harvard Univ, Sch Med, Boston, MA USA. [Kilmer, Suzanne L.] Laser & Skin Surg Ctr Northern Calif, Sacramento, CA USA. RP Ibrahimi, OA (reprint author), Connecticut Skin Inst, Stamford, CT 06905 USA. NR 68 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-84184-934-8; 978-1-84184-933-1 PY 2013 BP 94 EP 109 PG 16 WC Dermatology; Physics, Applied SC Dermatology; Physics GA BD4WN UT WOS:000361147900005 ER PT B AU Ibrahimi, OA Fitzpatrick, RE Goldman, MP Kilmer, SL AF Ibrahimi, Omar A. Fitzpatrick, Richard E. Goldman, Mitchel P. Kilmer, Suzanne L. BE Goldman, MP Fitzpatrick, RE Ross, EV Kilmer, SL Weiss, RA TI Skin resurfacing with ablative lasers SO LASERS AND ENERGY DEVICES FOR THE SKIN, 2ND EDITION LA English DT Article; Book Chapter ID CARBON-DIOXIDE LASER; ERBIUM-YAG LASER; FACIAL ACNE SCARS; COMPUTER-PATTERN GENERATOR; CO2-LASER TISSUE ABLATION; VERRUCOUS EPIDERMAL NEVI; RESIDUAL THERMAL-DAMAGE; ENERGY PULSED CO2-LASER; ANTI-MICROBIAL AGENTS; SWITCHED RUBY-LASER C1 [Ibrahimi, Omar A.] Connecticut Skin Inst, Stamford, CT 06905 USA. [Ibrahimi, Omar A.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Ibrahimi, Omar A.] Harvard Univ, Sch Med, Boston, MA USA. [Fitzpatrick, Richard E.; Goldman, Mitchel P.] Univ Calif San Diego, San Diego, CA 92103 USA. [Fitzpatrick, Richard E.; Goldman, Mitchel P.] Goldman Butterwick Fitzpatrick Groff & Fabi Cosme, San Diego, CA USA. [Kilmer, Suzanne L.] Laser & Skin Surg Ctr Northern Calif, Sacramento, CA USA. RP Ibrahimi, OA (reprint author), Connecticut Skin Inst, Stamford, CT 06905 USA. NR 296 TC 1 Z9 1 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-84184-934-8; 978-1-84184-933-1 PY 2013 BP 110 EP 161 PG 52 WC Dermatology; Physics, Applied SC Dermatology; Physics GA BD4WN UT WOS:000361147900006 ER PT B AU Garibyan, L Jalian, HR Avram, MM Weiss, RA AF Garibyan, Lilit Jalian, H. Ray Avram, Mathew M. Weiss, Robert A. BE Goldman, MP Fitzpatrick, RE Ross, EV Kilmer, SL Weiss, RA TI Body contouring: Noninvasive fat reduction SO LASERS AND ENERGY DEVICES FOR THE SKIN, 2ND EDITION LA English DT Article; Book Chapter ID INTENSITY FOCUSED ULTRASOUND; LEVEL LASER THERAPY; SUBCUTANEOUS FAT; ADIPOSE-TISSUE; RADIOFREQUENCY DEVICES; EFFICACY; CRYOLIPOLYSIS(TM); PANNICULITIS; SAFETY C1 [Garibyan, Lilit] Massachusetts Gen Hosp, Laser, Cosmet Ctr, Boston, MA 02114 USA. [Garibyan, Lilit; Jalian, H. Ray] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Garibyan, Lilit] Harvard Univ, Med Sch Boston, Dept Dermatol, Cambridge, MA 02138 USA. [Jalian, H. Ray] Massachusetts Gen Hosp, Laser & Cosmet Ctr, Boston, MA 02114 USA. [Jalian, H. Ray] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Avram, Mathew M.] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Weiss, Robert A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Weiss, Robert A.] Maryland Laser Skin & Vein Inst, Baltimore, MD USA. RP Garibyan, L (reprint author), Massachusetts Gen Hosp, Laser, Cosmet Ctr, Boston, MA 02114 USA. NR 30 TC 0 Z9 0 U1 2 U2 2 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-84184-934-8; 978-1-84184-933-1 PY 2013 BP 283 EP 292 PG 10 WC Dermatology; Physics, Applied SC Dermatology; Physics GA BD4WN UT WOS:000361147900012 ER PT J AU Pectasides, M Claus, F Lee, SI AF Pectasides, Melina Claus, Filip Lee, Susanna I. BA VanDeVelde, M Scholefield, H Plante, LA BF VanDeVelde, M Scholefield, H Plante, LA TI Imaging issues in maternal critical care SO MATERNAL CRITICAL CARE: A MULTIDISCIPLINARY APPROACH LA English DT Article; Book Chapter ID CT PULMONARY ANGIOGRAPHY; PREGNANT PATIENTS; POSTPARTUM HEMORRHAGE; ABDOMINAL-PAIN; HELICAL CT; PATIENT; SAFETY; EMBOLIZATION; ULTRASOUND; MANAGEMENT C1 [Pectasides, Melina; Lee, Susanna I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02138 USA. [Claus, Filip] Univ Hosp Leuven, Dept Radiol, Leuven, Belgium. RP Pectasides, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02138 USA. NR 49 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-1-107-01849-5 PY 2013 BP 230 EP 245 D2 10.1017/CBO9781139088084 PG 16 WC Anesthesiology; Obstetrics & Gynecology SC Anesthesiology; Obstetrics & Gynecology GA BD5LX UT WOS:000361596600023 ER PT B AU Conolly, S Maeovski, A Pauly, J Schenck, J Kwong, KK Chesler, DA Hu, XP Chen, W Patel, M Ugurbil, K AF Conolly, Steven Maeovski, Albert Pauly, John Schenck, John Kwong, Kenneth K. Chesler, David A. Hu, Xiaoping Chen, Wei Patel, Magbool Ugurbil, Kamil BE Analoui, M Bronzino, JD Peterson, DR TI Magnetic Resonance Imaging SO MEDICAL IMAGING: PRINCIPLES AND PRACTICES LA English DT Article; Book Chapter C1 [Conolly, Steven] Stanford Univ, Dept Biomed Engn, Stanford, CA 94305 USA. [Maeovski, Albert; Pauly, John] Stanford Univ, Dept Elect Engn, Stanford, CA 94305 USA. [Maeovski, Albert] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA. [Schenck, John] Gen Elect Corp Res & Dev Ctr, Schenectady, NY USA. [Kwong, Kenneth K.; Chesler, David A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hu, Xiaoping; Chen, Wei; Patel, Magbool; Ugurbil, Kamil] Univ Minnesota, Sch Med, Ctr Magnet Resonance Res, Minneapolis, MN 55455 USA. RP Conolly, S (reprint author), Stanford Univ, Dept Biomed Engn, Stanford, CA 94305 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-7103-4; 978-1-4398-7102-7 PY 2013 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BD7FI UT WOS:000362981200004 ER PT B AU Kwong, KK Chesler, DA AF Kwong, Kenneth K. Chesler, David A. BE Analoui, M Bronzino, JD Peterson, DR TI Functional MRI SO MEDICAL IMAGING: PRINCIPLES AND PRACTICES LA English DT Article; Book Chapter ID HUMAN VISUAL-CORTEX; MAGNETIC-RESONANCE IMAGE; HUMAN BRAIN ACTIVITY; MOTOR CORTEX; ARTERIAL WATER; TRANSVERSE RELAXATION; SENSORY STIMULATION; PHOTIC-STIMULATION; BLOOD OXYGENATION; SIGNAL CHANGES C1 [Kwong, Kenneth K.; Chesler, David A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Kwong, KK (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 60 TC 0 Z9 0 U1 1 U2 1 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-7103-4; 978-1-4398-7102-7 PY 2013 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BD7FI UT WOS:000362981200006 ER PT J AU Iyengar, AS Miller, PJ Loupe, JM Hollenbach, AD AF Iyengar, A. S. Miller, P. J. Loupe, J. M. Hollenbach, A. D. TI Phosphorylation of Pax3 Contributes to Melanoma Progression by Affecting Proliferation, Invasion, Migration, and Transformation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Iyengar, A. S.; Miller, P. J.; Loupe, J. M.; Hollenbach, A. D.] Louisiana State Univ, Hlth Sci Ctr, Genet, New Orleans, LA USA. [Iyengar, A. S.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1633 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348703128 ER PT J AU Joukov, V Walter, JC De Nicolo, A AF Joukov, V. Walter, J. C. De Nicolo, A. TI Cep192 scaffolds Aurora A and Plk1 in a kinase cascade that drives centrosome maturation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Joukov, V.; Walter, J. C.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [De Nicolo, A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [De Nicolo, A.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 997 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348701321 ER PT J AU Kuroda, TS Dor, YK Li, H Dagher, RK Tamayo, P Moreau, LA Mesirov, JP Pellman, D AF Kuroda, T. S. Dor, Y. Kaplan Li, H. Dagher, R. K. Tamayo, P. Moreau, L. A. Mesirov, J. P. Pellman, D. TI Selective targeting of chromosomally unstable cancer cells by the inhibition of VRK2 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Kuroda, T. S.; Dor, Y. Kaplan; Li, H.; Dagher, R. K.; Moreau, L. A.; Pellman, D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kuroda, T. S.; Dor, Y. Kaplan; Li, H.; Dagher, R. K.; Pellman, D.] Harvard Univ, Sch Med, Boston, MA USA. [Kuroda, T. S.] Mie Univ, Grad Sch Med, Tsu, Mie, Japan. [Tamayo, P.; Mesirov, J. P.] Broad Inst Harvard & MIT, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 859 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348701183 ER PT J AU Lazaro, JB Dreze, M Calkins, AS Schnorenberg, M Echelman, D Iglehart, JD AF Lazaro, J-B. Dreze, M. Calkins, A. S. Schnorenberg, M. Echelman, D. Iglehart, J. D. TI Purified DNA damage-recognition protein complexes, used in lieu of primary antibodies, to stain damaged DNA in situ. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Lazaro, J-B.; Dreze, M.; Calkins, A. S.; Schnorenberg, M.; Echelman, D.; Iglehart, J. D.] Dana Farber Canc Inst, Canc Biol, Boston, MA 02115 USA. [Lazaro, J-B.; Iglehart, J. D.] Harvard Univ, Sch Med, Surg, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 289 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348700032 ER PT J AU Lewis, WR Berbari, NF Malarkey, EB Pasek, RC Drummond, IA Rowe, SM Yoder, BK AF Lewis, W. R. Berbari, N. F. Malarkey, E. B. Pasek, R. C. Drummond, I. A. Rowe, S. M. Yoder, B. K. TI A Role for Gas8 in Left-Right Asymmetry and Motile and Primary Cilia SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Lewis, W. R.; Berbari, N. F.; Malarkey, E. B.; Rowe, S. M.; Yoder, B. K.] Univ Alabama Birmingham, Cell Dev & Integrat Biol, Birmingham, AL USA. [Pasek, R. C.] Vanderbilt Univ, Diabet Endocrinol & Metab Div, Nashville, TN 37235 USA. [Drummond, I. A.] Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1983 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348704090 ER PT J AU Martinelli, R Zeiger, AS Withfield, M Van Vliet, KJ Greenwood, J Carman, CV AF Martinelli, R. Zeiger, A. S. Withfield, M. Van Vliet, K. J. Greenwood, J. Carman, C. V. TI Cellular and Biomechanical Determinants of Leukocyte Diapedesis Migration Route SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Martinelli, R.; Carman, C. V.] Ctr Vasc Biol Res BIDMC & HMS, Med, Boston, MA USA. [Martinelli, R.; Greenwood, J.] UCL, Cell Biol, London, England. [Zeiger, A. S.; Withfield, M.; Van Vliet, K. J.] MIT, Mat Sci & Engn, Cambridge, MA 02139 USA. [Van Vliet, K. J.] MIT, Biol Engn, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 233 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348705515 ER PT J AU Martinelli, R Kamei, M Sage, PT Massol, R Varghese, L Sciuto, T Toporsian, M Dvorak, AM Kirchhausen, T Springer, TA Carman, CV AF Martinelli, R. Kamei, M. Sage, P. T. Massol, R. Varghese, L. Sciuto, T. Toporsian, M. Dvorak, A. M. Kirchhausen, T. Springer, T. A. Carman, C. V. TI Release of Cellular Tension Signals Self-Restorative Ventral Lamellipodia to Heal Barrier Micro-Wounds SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Martinelli, R.; Sage, P. T.; Toporsian, M.; Carman, C. V.] Harvard Univ, Sch Med, Med, Boston, MA 02115 USA. [Martinelli, R.; Sage, P. T.; Varghese, L.; Carman, C. V.] Beth Israel Deaconess Med Ctr, Ctr Vasc Biol Res, Boston, MA 02215 USA. [Kamei, M.] Natl Cerebral & Cardiovasc Ctr, Dept Anesthesiol, Osaka, Japan. [Massol, R.] Harvard Univ, Childrens Hosp, Sch Med, Pediat, Boston, MA 02115 USA. [Sciuto, T.; Dvorak, A. M.] Beth Israel Deaconess Med Ctr, Pathol, Boston, MA 02215 USA. [Kirchhausen, T.] Harvard Univ, Sch Med, Cell Biol, Boston, MA 02115 USA. [Springer, T. A.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 40 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348705322 ER PT J AU Martinelli, R Kamei, M Sage, PT Massol, R Varghese, L Sciuto, T Toporsian, M Dvorak, AM Kirchhausen, T Springer, TA Carman, CV AF Martinelli, R. Kamei, M. Sage, P. T. Massol, R. Varghese, L. Sciuto, T. Toporsian, M. Dvorak, A. M. Kirchhausen, T. Springer, T. A. Carman, C. V. TI Release of Cellular Tension Signals Self-Restorative Ventral Lamellipodia to Heal Barrier Micro-Wounds SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Martinelli, R.; Sage, P. T.; Toporsian, M.; Carman, C. V.] Harvard Univ, Sch Med, Med, Boston, MA USA. [Martinelli, R.; Sage, P. T.; Varghese, L.; Carman, C. V.] Beth Israel Deaconess Med Ctr, Vasc Biol Res Ctr, Boston, MA 02215 USA. [Kamei, M.] Natl Cerebral & Cardiovasc Ctr, Dept Anesthesiol, Osaka, Japan. [Massol, R.] Harvard Univ, Childrens Hosp, Sch Med, Pediat, Boston, MA 02115 USA. [Sciuto, T.; Dvorak, A. M.] Beth Israel Deaconess Med Ctr, Pathol, Boston, MA 02215 USA. [Kirchhausen, T.] Harvard Univ, Sch Med, Cell Biol, Boston, MA USA. [Springer, T. A.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1107 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348702011 ER PT J AU Martinelli, R Zeiger, AS Withfield, M Van Vliet, KJ Greenwood, J Carman, CV AF Martinelli, R. Zeiger, A. S. Withfield, M. Van Vliet, K. J. Greenwood, J. Carman, C. V. TI Cellular and Biomechanical Determinants of Leukocyte Diapedesis Migration Route SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Martinelli, R.; Carman, C. V.] BIDMC, Vasc Biol Res Ctr, Med, Boston, MA USA. [Martinelli, R.; Carman, C. V.] HMS, Boston, MA USA. [Martinelli, R.; Greenwood, J.] UCL, Cell Biol, London, England. [Zeiger, A. S.; Withfield, M.; Van Vliet, K. J.] MIT, Mat Sci & Engn, Cambridge, MA 02139 USA. [Van Vliet, K. J.] MIT, Biol Engn, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 641 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348700384 ER PT J AU Ortiz, A AF Ortiz, A. TI Steady-State Distribution of Protein Filaments SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Ortiz, A.] Univ Texas El Paso, Dept Math, El Paso, TX 79968 USA. [Ortiz, A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 2346 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348705056 ER PT J AU Ortiz, ZGR Pendergraft, W Prasad, A Means, TK AF Ortiz, Z. G. Ramirez Pendergraft, W. Prasad, A. Means, T. K. TI SCARFing the dead: The role of the scavenger receptor SCARF1 in efferocytosis and prevention of autoimmunity SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Ortiz, Z. G. Ramirez; Pendergraft, W.; Prasad, A.; Means, T. K.] Massachusetts Gen Hosp, CIID, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 2247 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348704353 ER PT J AU Pellman, DS AF Pellman, D. S. TI How Chromosome Segregation Errors Shape Cancer Genomes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Pellman, D. S.] Dana Farber Canc Inst, Pediat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 75 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348705357 ER PT J AU Salinthone, S Kerns, A Tsang, V Bourdette, D Carr, D AF Salinthone, S. Kerns, A. Tsang, V. Bourdette, D. Carr, D. TI Elucidating the mechanisms of action of dimethyl fumarate SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Salinthone, S.; Kerns, A.; Tsang, V.; Carr, D.] Portland VA Med Ctr, Res & Dev, Portland, OR USA. [Salinthone, S.; Bourdette, D.] Oregon Hlth & Sci Univ, Neurol, Portland, OR 97239 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1364 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348702268 ER PT J AU Zhang, H Ganem, N Pellman, D AF Zhang, H. Ganem, N. Pellman, D. TI The role of epigenetic and transcriptional variability during the evolution of potentially oncogenic tetraploids SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Zhang, H.; Pellman, D.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Ganem, N.] Boston Univ, Sch Med, Dept Pharmacol, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 2511 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348705221 ER PT J AU Zhu, X Hu, R Brissova, M Powers, A Gu, G Kaverina, I AF Zhu, X. Hu, R. Brissova, M. Powers, A. Gu, G. Kaverina, I. TI Microtubules negatively regulate insulin secretion in pancreatic beta-cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Zhu, X.; Hu, R.; Gu, G.; Kaverina, I.] Vanderbilt Univ, Med Ctr, Cell & Dev Biol, Nashville, TN USA. [Brissova, M.; Powers, A.] Vanderbilt Univ, Med Ctr, Dept Med, Div Diabet Endocrinol & Metab, Nashville, TN USA. [Powers, A.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Med Ctr, Nashville, TN 37232 USA. [Powers, A.] US Dept Vet Affairs, Tennessee Vally Healthcare Syst, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1185 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348702089 ER PT J AU Peeva, MG Tourville, JA Agam, Y Holland, B Manoach, DS Guenther, FH AF Peeva, M. G. Tourville, J. A. Agam, Y. Holland, B. Manoach, D. S. Guenther, F. H. TI White matter impairment in the speech network of individuals with autism spectrum disorder SO NEUROIMAGE-CLINICAL LA English DT Article DE Autism; ASD; Speech; Diffusion tensor imaging; Tractography; Communication AB Impairments in language and communication are core features of Autism Spectrum Disorder (ASD), and a substantial percentage of children with ASD do not develop speech. ASD is often characterized as a disorder of brain connectivity, and a number of studies have identified white matter impairments in affected individuals. The current study investigated white matter integrity in the speech network of high-functioning adults with ASD. Diffusion tensor imaging (DTI) scans were collected from 18 participants with ASD and 18 neurotypical participants. Probabilistic tractography was used to estimate the connection strength between ventral premotor cortex (vPMC), a cortical region responsible for speech motor planning, and five other cortical regions in the network of areas involved in speech production. We found a weaker connection between the left vPMC and the supplementary motor area in the ASD group. This pathway has been hypothesized to underlie the initiation of speech motor programs. Our results indicate that a key pathway in the speech production network is impaired in ASD, and that this impairment can occur even in the presence of normal language abilities. Therapies that result in normalization of this pathway may hold particular promise for improving speech output in ASD. (C) 013 The Authors. Published by Elsevier Inc. Open access under CC BY-NC-ND license. C1 [Peeva, M. G.; Tourville, J. A.; Guenther, F. H.] Boston Univ, Ctr Computat Neurosci & Neural Technol, Boston, MA 02215 USA. [Tourville, J. A.; Holland, B.; Guenther, F. H.] Boston Univ, Dept Speech Language & Hearing Sci, Boston, MA 02215 USA. [Agam, Y.; Manoach, D. S.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Agam, Y.; Manoach, D. S.; Guenther, F. H.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Guenther, F. H.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. RP Peeva, MG (reprint author), Boston Childrens Hosp, 300 Longwood Ave,CLS 14030-3, Boston, MA 02115 USA. EM maia.peeva@childrens.harvard.edu FU National Institute for Deafness and other Communication Disorders [R01 DC007683, R01 DC002852, P50 DC013027]; National Institute for Mental Health [R01 MH67720]; Mental Illness Neuroscience Discovery (MIND) Institute [DOE DE-FG02-99ER62764]; National Center for Research Resources [P41RR14075]; National Institute of Mental Health [F32 MH088081] FX This research was supported by the National Institute for Deafness and other Communication Disorders grants R01 DC007683 (FHG, PI), R01 DC002852 (FHG, PI), and P50 DC013027 (H. Tager-Flusberg, PI); National Institute for Mental Health grant R01 MH67720 (DSM, PI); Mental Illness Neuroscience Discovery (MIND) Institute grant DOE DE-FG02-99ER62764; the National Center for Research Resources grant P41RR14075; and National Institute of Mental Health grant F32 MH088081 (YA, PI). We thank Alfonso Nieto-Castanon and Jennifer Segawa for their contributions to the data analyses. NR 68 TC 3 Z9 3 U1 1 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2013 VL 3 BP 234 EP 241 DI 10.1016/j.nicl.2013.08.011 PG 8 WC Neuroimaging SC Neurosciences & Neurology GA V37LI UT WOS:000209276900026 PM 24273708 ER PT J AU Jalbrzikowski, M Jonas, R Senturk, D Patel, A Chow, C Green, MF Bearden, CE AF Jalbrzikowski, Maria Jonas, Rachel Senturk, Damla Patel, Arati Chow, Carolyn Green, Michael F. Bearden, Carrie E. TI Structural abnormalities in cortical volume, thickness, and surface area in 22q11.2 microdeletion syndrome: Relationship with psychotic symptoms SO NEUROIMAGE-CLINICAL LA English DT Article DE Copy number variation; Structural magnetic resonance imaging; Psychosis; Schizophrenia; Velocardiofacial syndrome AB Introduction: 22q11.2 deletion syndrome (22q11DS) represents one of the largest known genetic risk factors for psychosis, yet the neurobiological mechanisms underlying symptom development are not well understood. Here we conducted a cross-sectional study of 22q11DS to decompose cortical volume into its constituent parts, cortical thickness (CT) and surface area (SA), which are believed to have distinct neurodevelopmental origins. Methods: High-resolution T1-weighted scans were collected on 65 participants (31 22q11DS, 34 demographically comparable typically developing controls, 10-25 years old). Measures of cortical volume, CT, and SA were extracted from regions of interest using the FreeSurfer image analysis suite. Group differences and age-related trajectories in these structures, as well as their association with psychotic symptomatology, were assessed. Results: Relative to controls, 22q11DS participants showed bilateral volumetric reductions in the inferior temporal cortex, fusiform gyrus, anterior cingulate, superior parietal cortex, and cuneus, which were driven by decreased SA in these regions. 22q11DS participants also had increased volumes, driven by increased CT, in bilateral insula regions. 22q11DS youth had increased CT in frontal regions, particularly middle frontal and medial orbitofrontal cortices. A pattern of age-associated cortical thinning was observed in typically developing controls in brain regions associated with visual and sensory information-processing (i.e., left pericalcarine cortex and fusiform gyrus, right lingual and postcentral cortices). However, this relationship was disrupted in 22q11DS participants. Finally, correlational analyses revealed that increased CT in right medial orbitofrontal cortex was associated with increased positive symptom severity in 22q11DS. Conclusion: Differential disruptions of CT and SA in distinct cortical regions in 22q11DS may indicate abnormalities in distinct developmental neural processes. Further, neuroanatomic abnormalities in medial frontal brain structures disproportionately affected in idiopathic schizophrenia were associated with psychotic symptom severity in 22q11DS youth, suggesting that disrupted biological processes in these cortical regions may underlie development of psychotic symptoms, both in 22q11DS and in the broader population. (C) 2013 The Authors. Published by Elsevier Inc. C1 [Jalbrzikowski, Maria; Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Jalbrzikowski, Maria; Jonas, Rachel; Patel, Arati; Chow, Carolyn; Green, Michael F.; Bearden, Carrie E.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Senturk, Damla] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA. [Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Mental Illness Res Educ & Clin Ctr VISN22, Los Angeles, CA 90073 USA. RP Bearden, CE (reprint author), UCLA Psychiat & Biobehav Sci, Box 956968,300 Med Plaza,Rm 2267, Los Angeles, CA 90095 USA. EM cbearden@mednet.ucla.edu FU NICHD NIH HHS [R01 HD065280]; NIMH NIH HHS [R01 MH085953] NR 73 TC 27 Z9 27 U1 2 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2013 VL 3 BP 405 EP 415 DI 10.1016/j.nicl.2013.09.013 PG 11 WC Neuroimaging SC Neurosciences & Neurology GA V37LI UT WOS:000209276900044 PM 24273724 ER PT J AU Mueller-Pfeiffer, C Schick, M Schulte-Vels, T O'Gorman, R Michels, L Martin-Soelch, C Blair, JR Rufer, M Schnyder, U Zeffiro, T Hasler, G AF Mueller-Pfeiffer, Christoph Schick, Matthis Schulte-Vels, Thomas O'Gorman, Ruth Michels, Lars Martin-Soelch, Chantal Blair, James R. Rufer, Michael Schnyder, Ulrich Zeffiro, Thomas Hasler, Gregor TI Atypical visual processing in posttraumatic stress disorder SO NEUROIMAGE-CLINICAL LA English DT Article DE Visual system; Ventral stream; Dorsal stream; fMRI; International Affective Picture System; Sensory perception AB Background: Many patients with Posttraumatic Stress Disorder (PTSD) feel overwhelmed in situations with high levels of sensory input, as in crowded situations with complex sensory characteristics. These difficulties might be related to subtle sensory processing deficits similar to those that have been found for sounds in electrophysiological studies. Method: Visual processing was investigated with functional magnetic resonance imaging in trauma-exposed participants with (N = 18) and without PTSD (N = 21) employing a picture-viewing task. Results: Activity observed in response to visual scenes was lower in PTSD participants 1) in the ventral stream of the visual system, including striate and extrastriate, inferior temporal, and entorhinal cortices, and 2) in dorsal and ventral attention systems (P < 0.05, FWE-corrected). These effects could not be explained by the emotional salience of the pictures. Conclusions: Visual processing was substantially altered in PTSD in the ventral visual stream, a component of the visual system thought to be responsible for object property processing. Together with previous reports of subtle auditory deficits in PTSD, these findings provide strong support for potentially important sensory processing deficits, whose origins may be related to dysfunctional attention processes. (C) 2013 The Authors. Published by Elsevier Inc. Open access under CC BY license. C1 [Mueller-Pfeiffer, Christoph; Schick, Matthis; Schulte-Vels, Thomas; Rufer, Michael; Schnyder, Ulrich] Univ Zurich Hosp, Dept Psychiat & Psychotherapy, CH-8091 Zurich, Switzerland. [Mueller-Pfeiffer, Christoph] Psychiat Serv Cty St Gallen North, Ctr Educ & Res COEUR, Wil, Switzerland. [Mueller-Pfeiffer, Christoph] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Mueller-Pfeiffer, Christoph] Harvard Univ, Sch Med, Boston, MA USA. [O'Gorman, Ruth; Michels, Lars] Univ Childrens Hosp, Ctr MR Res, Zurich, Switzerland. [Michels, Lars] Univ Zurich Hosp, Inst Neuroradiol, CH-8091 Zurich, Switzerland. [Martin-Soelch, Chantal] Univ Fribourg, Dept Clin Psychol, CH-1700 Fribourg, Switzerland. [Blair, James R.] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. [Zeffiro, Thomas] Massachusetts Gen Hosp, Neural Syst Grp, Boston, MA 02114 USA. [Hasler, Gregor] Univ Bern, Psychiat Univ Hosp, Bern, Switzerland. RP Mueller-Pfeiffer, C (reprint author), Univ Zurich Hosp, Dept Psychiat & Psychotherapy, Culmannstr 8, CH-8091 Zurich, Switzerland. EM christoph.mueller-pfeiffer@access.uzh.ch RI Hasler, Gregor/E-4845-2012; OI Hasler, Gregor/0000-0002-8311-0138; Rufer, Michael/0000-0003-4964-4213; O'Gorman, Ruth/0000-0001-5932-7786 FU "Stiftung fur wissenschaftliche Forschung" (University of Zurich); Stanley Thomas Johnson Foundation (Bern); "Helen Bieber-Fonds" (University of Zurich) FX The study was funded by the "Stiftung fur wissenschaftliche Forschung" (University of Zurich), Stanley Thomas Johnson Foundation (Bern), and the "Helen Bieber-Fonds" (University of Zurich). The authors report no competing interests. We are grateful to Dr Roger Pitman for helpful suggestions. NR 76 TC 8 Z9 8 U1 4 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2013 VL 3 BP 531 EP 538 DI 10.1016/j.nicl.2013.08.009 PG 8 WC Neuroimaging SC Neurosciences & Neurology GA V37LI UT WOS:000209276900057 PM 24371791 ER PT J AU van Dellen, E Hamer, PCDW Douw, L Klein, M Heimans, JJ Stam, CJ Reijneveld, JC Hillebrand, A AF van Dellen, E. Hamer, P. C. de Witt Douw, L. Klein, M. Heimans, J. J. Stam, C. J. Reijneveld, J. C. Hillebrand, A. TI Connectivity in MEG resting-state networks increases after resective surgery for low-grade glioma and correlates with improved cognitive performance SO NEUROIMAGE-CLINICAL LA English DT Article DE Glioma; Resective surgery; Cognition; Magnetoencephalography; Resting-state networks; Functional connectivity ID DEFAULT MODE NETWORK; BRAIN-TUMOR PATIENTS; FUNCTIONAL CONNECTIVITY; UNIFIED SEGMENTATION; MAGNETOENCEPHALOGRAPHY; ORGANIZATION; LESIONS; LOCATIONS; DYNAMICS; CORTEX AB Purpose: Low-grade glioma (LGG) patients often have cognitive deficits. Several disease-and treatment related factors affect cognitive processing. Cognitive outcome of resective surgery is unpredictable, both for improvement and deterioration, especially for complex domains such as attention and executive functioning. MEG analysis of resting-state networks (RSNs) is a good candidate for presurgical prediction of cognitive outcome. In this study, we explore the relation between alterations in connectivity of RSNs and changes in cognitive processing after resective surgery, as a stepping stone to ultimately predict postsurgical cognitive outcome. Methods: Ten patients with LGG were included, who had no adjuvant therapy. MEG recording and neuropsychological assessment were obtained before and after resective surgery. MEG data were recorded during a no-task eyes-closed condition, and projected to the anatomical space of the AAL atlas. Alterations in functional connectivity, as characterized by the phase lag index (PLI), within the default mode network (DMN), executive control network (ECN), and left-and right-sided frontoparietal networks (FPN) were compared to cognitive changes. Results: Lower alpha band DMN connectivity was increased after surgery, and this increase was related to improved verbal memory functioning. Similarly, right FPN connectivity was increased after resection in the upper alpha band, which correlated with improved attention, working memory and executive functioning. Discussion: Increased alpha band RSN functional connectivity in MEG recordings correlates with improved cognitive outcome after resective surgery. The mechanisms resulting in functional connectivity alterations after resection remain to be elucidated. Importantly, our findings indicate that connectivity of MEG RSNs may be used for presurgical prediction of cognitive outcome in future studies. (C) 2012 The Authors. Published by Elsevier Inc. Open access under CC BY license. C1 [van Dellen, E.; Douw, L.; Heimans, J. J.; Reijneveld, J. C.] Vrije Univ Amsterdam Med Ctr, Dept Neurol, NL-1007 MB Amsterdam, Netherlands. [Hamer, P. C. de Witt] Vrije Univ Amsterdam Med Ctr, Neurosurg Ctr Amsterdam, NL-1007 MB Amsterdam, Netherlands. [Douw, L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Douw, L.] Harvard Univ, Sch Med, Boston, MA USA. [Stam, C. J.; Hillebrand, A.] Vrije Univ Amsterdam Med Ctr, Dept Clin Neurophysiol, NL-1007 MB Amsterdam, Netherlands. [Stam, C. J.; Hillebrand, A.] Vrije Univ Amsterdam Med Ctr, MEG Ctr, NL-1007 MB Amsterdam, Netherlands. [Klein, M.] Vrije Univ Amsterdam Med Ctr, Dept Med Psychol, NL-1007 MB Amsterdam, Netherlands. RP van Dellen, E (reprint author), Vrije Univ Amsterdam Med Ctr, Dept Neurol, POB 7057, NL-1007 MB Amsterdam, Netherlands. EM E.vanDellen@vumc.nl RI De Witt Hamer, Philip/E-7630-2013; Klein, Martin/C-4192-2012 OI De Witt Hamer, Philip/0000-0003-2988-8544; Klein, Martin/0000-0003-4160-5746 FU Dutch Epilepsy Foundation (NEF) [09-09]; Rubicon grant of the Netherlands Organisation for Scientific Research (NWO); Amsterdam Brain Imaging Platform (ABIP), Amsterdam, The Netherlands FX The authors would like to thank G. Engels and N. Sijsma for their assistance with data analysis; W. Cleijne for her assistance with neuropsychological assessments; P. Tewarie and K. Olde Dubbelink for their input on the definition of resting-state networks; and the MEG technicians of the Department of Clinical Neurophysiology, P.J. Ris and K. Plugge, for technical assistance. E. van Dellen is supported by the Dutch Epilepsy Foundation (NEF) grant 09-09. L. Douw is supported by the Rubicon grant of the Netherlands Organisation for Scientific Research (NWO). Scanning costs in part funded by the Amsterdam Brain Imaging Platform (ABIP), Amsterdam, The Netherlands. NR 50 TC 15 Z9 15 U1 4 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2013 VL 2 BP 1 EP 7 DI 10.1016/j.nicl.2012.10.007 PG 7 WC Neuroimaging SC Neurosciences & Neurology GA V37LH UT WOS:000209276800001 ER PT J AU Barron, DS Fox, PM Laird, AR Robinson, JL Fox, PT AF Barron, Daniel S. Fox, P. Mickle Laird, Angela R. Robinson, Jennifer L. Fox, Peter T. TI Thalamic medial dorsal nucleus atrophy in medial temporal lobe epilepsy: A VBM meta-analysis SO NEUROIMAGE-CLINICAL LA English DT Article DE Hippocampal sclerosis; Cortical localization; Volumetric MRI; All epilepsy/seizures ID VOXEL-BASED MORPHOMETRY; WHITE-MATTER; FUNCTIONAL CONNECTIVITY; NETWORK ATROPHY; BRAIN; GRAY; SCLEROSIS; INVOLVEMENT; ACTIVATION; CORTEX AB Purpose: Medial temporal lobe epilepsy (MTLE) is associated with MTLE network pathology within and beyond the hippocampus. The purpose of this meta-analysis was to identify consistent MTLE structural change to guide subsequent targeted analyses of these areas. Methods: We performed an anatomic likelihood estimation (ALE) meta-analysis of 22 whole-brain voxel-based morphometry experiments from 11 published studies. We grouped these experiments in three ways. We then constructed a meta-analytic connectivity model (MACM) for regions of consistent MTLE structural change as reported by the ALE analysis. Key findings: ALE reported spatially consistent structural change across VBM studies only in the epileptogenic hippocampus and the bilateral thalamus; within the thalamus, the medial dorsal nucleus of the thalamus (MDN thalamus) represented the greatest convergence (P<0.05 corrected for multiple comparisons). The subsequent MACM for the hippocampus and ipsilateral MDN thalamus demonstrated that the hippocampus and ipsilateral MDN thalamus functionally co-activate and are nodes within the same network, suggesting that MDN thalamic damage could result from MTLE network excitotoxicity. Significance: Notwithstanding our large sample of studies, these findings are more restrictive than previous reports and demonstrate the utility of our inclusion filters and of recently modified meta-analytic methods in approximating clinical relevance. Thalamic pathology is commonly observed in animal and human studies, suggesting it could be a clinically useful indicator. Thalamus-specific research as a clinical marker awaits further investigation. (C) 2012 The Authors. Published by Elsevier Inc. Open access under CC BY license. C1 [Barron, Daniel S.; Fox, P. Mickle; Laird, Angela R.; Fox, Peter T.] UT Hlth Sci Ctr, Res Imaging Inst, San Antonio, TX USA. [Robinson, Jennifer L.] Scott & White Mem Hosp & Clin, Temple, TX USA. [Laird, Angela R.] Florida Int Univ, Miami, FL 33199 USA. [Fox, Peter T.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Barron, DS (reprint author), Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM barrond@uthscsa.edu RI Fox, Peter/B-4725-2010 OI Fox, Peter/0000-0002-0465-2028 FU National Institute of Health (NIMH) [RO1 MH074457] FX We thank Kristin S. Budde for her valuable edits. We also thank Kimberly Ray and Juan Saenz for their technical assistance. This study was supported by funds from the National Institute of Health (NIMH: RO1 MH074457). NR 52 TC 9 Z9 10 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2013 VL 2 BP 25 EP 32 DI 10.1016/j.nicl.2012.11.004 PG 8 WC Neuroimaging SC Neurosciences & Neurology GA V37LH UT WOS:000209276800004 PM 24179755 ER PT J AU Whitwell, JL Tosakulwong, N Weigand, SD Senjem, ML Lowe, VJ Gunter, JL Boeve, BF Knopman, DS Dickerson, BC Petersen, RC Jack, CR AF Whitwell, Jennifer L. Tosakulwong, Nirubol Weigand, Stephen D. Senjem, Matthew L. Lowe, Val J. Gunter, Jeffrey L. Boeve, Bradley F. Knopman, David S. Dickerson, Bradford C. Petersen, Ronald C. Jack, Clifford R., Jr. TI Does amyloid deposition produce a specific atrophic signature in cognitively normal subjects? SO NEUROIMAGE-CLINICAL LA English DT Article DE Amyloid; Preclinical; Alzheimer's disease; Freesurfer; Voxel-based morphometry; Cognitively normal ID VOXEL-BASED MORPHOMETRY; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; ALZHEIMERS-DISEASE; HIPPOCAMPAL ATROPHY; CORTICAL THICKNESS; ELDERLY SUBJECTS; AD DEMENTIA; MILD; IMPAIRMENT AB The objective of our study was to evaluate whether cognitively normal (CN) elderly participants showing elevated cortical beta-amyloid (A beta) deposition have a consistent neuroanatomical signature of brain atrophy that may characterize preclinical Alzheimer's disease (AD). 115 CN participants who were A beta-positive (CN+) by amyloid PET imaging; 115 CN participants who were A beta-negative (CN-); and 88 A beta-positive mild cognitive impairment or AD participants (MCI/AD+) were identified. Cortical thickness (FreeSurfer) and gray matter volume (SPM5) were measured for 28 regions-of-interest (ROIs) across the brain and compared across groups. ROIs that best discriminated CN- from CN+ differed for FreeSurfer cortical thickness and SPM5 gray matter volume. Group-wise discrimination was poor with a high degree of uncertainty in terms of the rank ordering of ROIs. In contrast, both techniques showed strong and consistent findings comparing MCI/AD+ to both CN- and CN+ groups, with entorhinal cortex, middle and inferior temporal lobe, inferior parietal lobe, and hippocampus providing the best discrimination for both techniques. Concordance across techniques was higher for the CN- and CN+ versus MCI/AD+ comparisons, compared to the CN- versus CN+ comparison. The weak and inconsistent nature of the findings across technique in this study cast doubt on the existence of a reliable neuroanatomical signature of preclinical AD in elderly PiB-positive CN participants. (C) 2013 The Authors. Published by Elsevier Inc. Open access under CC BY license. C1 [Whitwell, Jennifer L.; Lowe, Val J.; Jack, Clifford R., Jr.] Mayo Clin, Dept Radiol, Rochester, MN 55905 USA. [Tosakulwong, Nirubol; Weigand, Stephen D.] Mayo Clin, Dept Hlth Sci Res Biostat, Rochester, MN 55905 USA. [Senjem, Matthew L.; Gunter, Jeffrey L.] Mayo Clin, Dept Informat Technol, Rochester, MN 55905 USA. [Boeve, Bradley F.; Knopman, David S.; Petersen, Ronald C.] Mayo Clin, Dept Neurol, Rochester, MN 55905 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Dickerson, Bradford C.] Harvard Univ, Sch Med, Boston, MA USA. [Petersen, Ronald C.] Mayo Clin, Dept Epidemiol, Rochester, MN 55905 USA. RP Whitwell, JL (reprint author), Mayo Clin, 200 1st St SW, Rochester, MN 55905 USA. EM Whitwell.jennifer@mayo.edu FU NIH [P50-AG16574, U01-AG06786, R01-AG11378] FX This study was supported by NIH grants P50-AG16574, U01-AG06786, and R01-AG11378. The funding organizations played no role in the conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript. NR 40 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2013 VL 2 BP 249 EP 257 DI 10.1016/j.nicl.2013.01.006 PG 9 WC Neuroimaging SC Neurosciences & Neurology GA V37LH UT WOS:000209276800029 PM 24179779 ER PT J AU Maeda, Y Kettner, N Sheehan, J Kim, J Cina, S Malatesta, C Gerber, J McManus, C Mezzacappa, P Morse, LR Audette, J Napadow, V AF Maeda, Yumi Kettner, Norman Sheehan, James Kim, Jieun Cina, Stephen Malatesta, Cristina Gerber, Jessica McManus, Claire Mezzacappa, Pia Morse, Leslie R. Audette, Joseph Napadow, Vitaly TI Altered brain morphometry in carpal tunnel syndrome is associated with median nerve pathology SO NEUROIMAGE-CLINICAL LA English DT Article DE Nerve conduction velocity (NCV); Diffusion tensor imaging (DTI); Voxel-based morphometry (VBM); Fractional anisotropy (FA); Axial diffusivity (AD); Radial diffusivity (RD) ID SOMATOSENSORY CORTICAL PLASTICITY; SELF-ADMINISTERED QUESTIONNAIRE; DIFFUSION-TENSOR; FUNCTIONAL REORGANIZATION; NEUROPATHIC PAIN; SPINAL-CORD; BACK-PAIN; MRI; ANATOMY; HUMANS AB Objective: Carpal tunnel syndrome (CTS) is a common median nerve entrapment neuropathy characterized by pain, paresthesias, diminished peripheral nerve conduction velocity (NCV) and maladaptive functional brain neuroplasticity. We evaluated structural reorganization in brain gray matter (GM) and white matter (WM) and whether such plasticity is linked to altered median nerve function in CTS. Methods: We performed NCV testing, T1-weighted structural MRI, and diffusion tensor imaging (DTI) in 28 CTS and 28 age-matched healthy controls (HC). Voxel-based morphometry (VBM) contrasted regional GM volume for CTS versus HC. Significant clusters were correlated with clinical metrics and served as seeds to define associated WM tracts using DTI data and probabilistic tractography. Within these WM tracts, fractional anisotropy (FA), axial (AD) and radial (RD) diffusivity were evaluated for group differences and correlations with clinical metrics. Results: For CTS subjects, GM volume was significantly reduced in contralesional S1 (hand-area), pulvinar and frontal pole. GM volume in contralesional S1 correlated with median NCV. NCV was also correlated with RD and was negatively correlated with FA within U-fiber cortico-cortical association tracts identified from the contralesional S1 VBM seed. Conclusions: Our study identified clear morphometric changes in the CTS brain. This central morphometric change is likely secondary to peripheral nerve pathology and altered somatosensory afference. Enhanced axonal coherence and myelination within cortico-cortical tracts connecting primary somatosensory and motor areas may accompany peripheral nerve deafferentation. As structural plasticity was correlated with NCV and not symptomatology, the former may be a better determinant of appropriate clinical intervention for CTS, including surgery. (C) 2013 The Authors. Published by Elsevier Inc. C1 [Maeda, Yumi; Kim, Jieun; Cina, Stephen; Gerber, Jessica; Mezzacappa, Pia; Napadow, Vitaly] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Maeda, Yumi; Kettner, Norman; Napadow, Vitaly] Univ Programs, Logan Coll Chiropractic, Dept Radiol, Chesterfield, MO 63017 USA. [Sheehan, James] Massachusetts Gen Hosp, Dept Gastroenterol, Charlestown, MA 02129 USA. [Malatesta, Cristina; McManus, Claire] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Medford, MA 02155 USA. [Morse, Leslie R.] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Audette, Joseph] Atrius Hlth, Harvard Vanguard Med Associates, Dept Pain Med, Boston, MA 02215 USA. RP Maeda, Y (reprint author), 2301 149 Thirteenth St, Charlestown, MA 02129 USA. EM ymaeda@nmr.mgh.harvard.edu; Norman.Kettner@logan.edu; jds69@nmr.mgh.harvard.edu; seesaw@nmr.mgh.harvard.edu; stephencina@hotmail.com; cmalatesta@partners.org; jgerber@nmr.mgh.harvard.edu; mcmanusacupuncture@me.com; pia.hugus@gmail.com; LMorse4@PARTNERS.ORG; Joseph_Audette@vmed.org; vitaly@nmr.mgh.harvard.edu RI Morse, Leslie/C-9442-2015 OI Morse, Leslie/0000-0002-7426-6341 FU NCCAM; National Institutes of Health [R01-AT004714, R01-AT004714-02S1, P01-AT002048]; National Center for Research Resources (NCRR) [P41RR14075, S10RR021110] FX This work was supported by the NCCAM, National Institutes of Health [R01-AT004714, R01-AT004714-02S1, P01-AT002048], as well as by the National Center for Research Resources (NCRR) [P41RR14075, S10RR021110]. NR 44 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2013 VL 2 BP 313 EP 319 DI 10.1016/j.nicl.2013.02.001 PG 7 WC Neuroimaging SC Neurosciences & Neurology GA V37LH UT WOS:000209276800036 PM 23799199 ER PT J AU Jiang, X Bollich, A Cox, P Hyder, E James, J Gowani, SA Hadjikhani, N Blanz, V Manoach, DS Barton, JJS Gaillard, WD Riesenhuber, M AF Jiang, Xiong Bollich, Angela Cox, Patrick Hyder, Eric James, Joette Gowani, Saqib Ali Hadjikhani, Nouchine Blanz, Volker Manoach, Dara S. Barton, Jason J. S. Gaillard, William D. Riesenhuber, Maximilian TI A quantitative link between face discrimination deficits and neuronal selectivity for faces in autism SO NEUROIMAGE-CLINICAL LA English DT Article DE Face; Autism; ASD; fMRI; fMRI-RA; Local correlation ID LATERAL OCCIPITAL COMPLEX; INFERIOR TEMPORAL CORTEX; CEREBRAL-BLOOD-FLOW; SPECTRUM DISORDERS; FUSIFORM GYRUS; VISUAL-CORTEX; FUNCTIONING AUTISM; ASPERGER-SYNDROME; TASK-DIFFICULTY; NEURAL SYSTEMS AB Individuals with Autism Spectrum Disorder (ASD) appear to show a general face discrimination deficit across a range of tasks including social-emotional judgments as well as identification and discrimination. However, functional magnetic resonance imaging (fMRI) studies probing the neural bases of these behavioral differences have produced conflicting results: while some studies have reported reduced or no activity to faces in ASD in the Fusiform Face Area (FFA), a key region in human face processing, others have suggested more typical activation levels, possibly reflecting limitations of conventional fMRI techniques to characterize neuron-level processing. Here, we test the hypotheses that face discrimination abilities are highly heterogeneous in ASD and are mediated by FFA neurons, with differences in face discrimination abilities being quantitatively linked to variations in the estimated selectivity of face neurons in the FFA. Behavioral results revealed a wide distribution of face discrimination performance in ASD, ranging from typical performance to chance level performance. Despite this heterogeneity in perceptual abilities, individual face discrimination performance was well predicted by neural selectivity to faces in the FFA, estimated via both a novel analysis of local voxel-wise correlations, and the more commonly used fMRI rapid adaptation technique. Thus, face processing in ASD appears to rely on the FFA as in typical individuals, differing quantitatively but not qualitatively. These results for the first time mechanistically link variations in the ASD phenotype to specific differences in the typical face processing circuit, identifying promising targets for interventions. (C) 2013 The Authors. Published by Elsevier Inc. C1 Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20007 USA. [Gaillard, William D.] Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20007 USA. [Bollich, Angela; James, Joette] Childrens Natl Med Ctr, Ctr Autism Spectrum Disorder, Washington, DC 20010 USA. [Bollich, Angela; James, Joette; Gaillard, William D.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Hadjikhani, Nouchine] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Gowani, Saqib Ali] Aga Khan Univ, Karachi 74800, Pakistan. [Hadjikhani, Nouchine] Swiss Fed Inst Technol, CH-1015 Lausanne, Switzerland. [Blanz, Volker] Univ Siegen, D-57076 Siegen, Germany. [Barton, Jason J. S.] Univ British Columbia, Vancouver, BC V6T 1Z4, Canada. RP Riesenhuber, M (reprint author), Georgetown Univ, Med Ctr, Dept Neurosci, Res Bldg Room WP-12,3970 Reservoir Rd NW, Washington, DC 20007 USA. EM mr287@georgetown.edu OI Riesenhuber, Maximilian/0000-0002-5744-0408; Hadjikhani, Nouchine/0000-0003-4075-3106 FU Autism Speaks Foundation; NIMH [R01MH076281]; NSF [0449743]; SNF [PPOOB-110741]; NIH IDDRC [P30HD40677]; NIH GCRC [M01-RR13297] FX We thank Joshua O. Goh for discussions, and Greg Wallace, Alex Martin, and Lauren Kenworthy for help with subject recruitment. Additional subjects were recruited with the assistance of the Interactive Autism Network (IAN) Research Database at the Kennedy Krieger Institute and Johns Hopkins Medicine - Baltimore, sponsored by the Autism Speaks Foundation. The research reported in this paper was supported by NIMH grant R01MH076281 and NSF grant 0449743 (to M.R.), SNF PPOOB-110741 (to N.H.), as well as NIH IDDRC P30HD40677, and NIH GCRC M01-RR13297. NR 70 TC 9 Z9 9 U1 2 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2013 VL 2 BP 320 EP 331 DI 10.1016/j.nicl.2013.02.002 PG 12 WC Neuroimaging SC Neurosciences & Neurology GA V37LH UT WOS:000209276800037 PM 24179786 ER PT J AU Holzel, BK Hoge, EA Greve, DN Gard, T Creswell, JD Brown, KW Barrett, LF Schwartz, C Vaitl, D Lazar, SW AF Hoelzel, Britta K. Hoge, Elizabeth A. Greve, Douglas N. Gard, Tim Creswell, J. David Brown, Kirk Warren Barrett, Lisa Feldman Schwartz, Carl Vaitl, Dieter Lazar, Sara W. TI Neural mechanisms of symptom improvements in generalized anxiety disorder following mindfulness training SO NEUROIMAGE-CLINICAL LA English DT Article DE Generalized anxiety disorder; Emotion regulation; Mindfulness; Intervention; Longitudinal; Amygdala; Prefrontal cortex; Connectivity; Ventrolateral prefrontal cortex; Beck Anxiety Inventory; Stress ID PREFRONTAL CORTEX ACTIVATION; SURFACE-BASED ANALYSIS; EMOTION REGULATION; CORTICAL SURFACE; FUNCTIONAL MRI; STRESS REDUCTION; AMYGDALA RESPONSES; ANTERIOR CINGULATE; COORDINATE SYSTEM; COGNITIVE CONTROL AB Mindfulness training aims to impact emotion regulation. Generalized anxiety disorder (GAD) symptoms can be successfully addressed through mindfulness-based interventions. This preliminary study is the first to investigate neural mechanisms of symptom improvements in GAD following mindfulness training. Furthermore, we compared brain activation between GAD patients and healthy participants at baseline. 26 patientswith a current DSM-IV GAD diagnosiswere randomized to an 8-week Mindfulness Based Stress Reduction (MBSR, N = 15) or a stress management education (SME, N = 11) active control program. 26 healthy participants were included for baseline comparisons. BOLD response was assessed with fMRI during affect labeling of angry and neutral facial expressions. At baseline, GAD patients showed higher amygdala activation than healthy participants in response to neutral, but not angry faces, suggesting that ambiguous stimuli reveal stronger reactivity in GAD patients. In patients, amygdala activation in response to neutral faces decreased following both interventions. BOLD response in ventrolateral prefrontal regions (VLPFC) showed greater increase in MBSR than SME participants. Functional connectivity between amygdala and PFC regions increased significantly pre-to post-intervention within the MBSR, but not SME group. Both, change in VLPFC activation and amygdala-prefrontal connectivity were correlated with change in Beck Anxiety Inventory (BAI) scores, suggesting clinical relevance of these changes. Amygdala-prefrontal connectivity turned from negative coupling (typically seen in down-regulation of emotions), to positive coupling; potentially suggesting a unique mechanism of mindfulness. Findings suggest that in GAD, mindfulness training leads to changes in fronto-limbic areas crucial for the regulation of emotion; these changes correspond with reported symptom improvements. (C) 2013 The Authors. Published by Elsevier Inc. C1 [Hoelzel, Britta K.; Hoge, Elizabeth A.; Greve, Douglas N.; Gard, Tim; Barrett, Lisa Feldman; Schwartz, Carl; Lazar, Sara W.] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Hoelzel, Britta K.; Gard, Tim; Vaitl, Dieter] Univ Giessen, Bender Inst Neuroimaging, D-35394 Giessen, Germany. [Creswell, J. David] Carnegie Melon Univ, Dept Psychol, Pittsburgh, PA 15213 USA. [Brown, Kirk Warren] Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA. [Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. RP Holzel, BK (reprint author), Massachusetts Gen Hosp, 120 2nd Ave, Charlestown, MA 02129 USA. EM britta@nmr.mgh.harvard.edu; ehoge@partners.org; greve@nmr.mgh.harvard.edu; tgard@nmr.mgh.harvard.edu; creswell@cmu.edu; kwbrown@vcu.edu; l.barrett@neu.edu; carl_Schwartz@hms.harvard.edu; vaitl@bion.de; lazar@nmr.mgh.harvard.edu RI Lazar, Sara/G-3809-2012; Hoge, Elizabeth/H-5879-2012 OI Lazar, Sara/0000-0003-1126-8363; Hoge, Elizabeth/0000-0002-5513-2292 FU Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme [5K23AT004432] FX This research was funded by a Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme to B.K.H., grant 5K23AT004432 from the National Institutes of Health to E.A.H., a Varela research grant by the Mind and Life Institute to B.K.H., and grant R21-AT003425 from the National Institutes of Health-NCCAM to S.W.L. This research was carried out at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41RR14075, a P41 Regional Resource supported by the Biomedical Technology Program of the National Center for Research Resources (NCRR), National Institutes of Health. This work also involved the use of instrumentation supported by the NCRR Shared Instrumentation Grant Program; specifically, grant numbers 1S10RR023401, S10RR019307, and 1S10RR023043. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors declare no conflicts of interest. B.K.H. takes responsibility for the integrity of the data and the accuracy of the data analysis. We thank Zayda Vallejo for conducting the MBSR courses, Jennifer Johnston for conducting the SME courses, Narayan Brach and Christina Metcalf for support in data collection, and Andrea Hermann, Markus Graf, and Rudolf Stark for helpful comments on this manuscript. This study was registered with ClinicalTrials. gov (Identifier NCT01128309, Title: "Stress Reduction and Anxiety: Effects on the Function and Structure of the Brain", http://clinicaltrials.gov/ct2/results?term= NCT01128309). NR 92 TC 45 Z9 45 U1 12 U2 35 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2013 VL 2 BP 448 EP 458 DI 10.1016/j.nicl.2013.03.011 PG 11 WC Neuroimaging SC Neurosciences & Neurology GA V37LH UT WOS:000209276800050 PM 24179799 ER PT J AU Barysheva, M Jahanshad, N Foland-Ross, L Altshuler, LL Thompson, PM AF Barysheva, Marina Jahanshad, Neda Foland-Ross, Lara Altshuler, Lori L. Thompson, Paul M. TI White matter microstructural abnormalities in bipolar disorder: A whole brain diffusion tensor imaging study SO NEUROIMAGE-CLINICAL LA English DT Article DE Bipolar disorder; White matter; Neuroimaging; DTI; Brain mapping; Fractional anisotropy ID DECLARATIVE MEMORY IMPAIRMENT; VOXEL-BASED MORPHOMETRY; SPATIAL STATISTICS; CORPUS-CALLOSUM; IN-VIVO; ORBITOFRONTAL CORTEX; HIPPOCAMPAL COMPLEX; RESERVE HYPOTHESIS; PREFRONTAL CORTEX; 1ST-EPISODE MANIA AB Background: Bipolar disorder (BD) is a chronic mental illness characterized by severe disruptions in mood and cognition. Diffusion tensor imaging (DTI) studies suggest that white matter (WM) tract abnormalities may contribute to the clinical hallmarks of the disorder. Using DTI and whole brain voxel-based analysis, we mapped the profile of WM anomalies in BD. All patients in our sample were euthymic and lithium free when scanned. Methods: Diffusion-weighted and T1-weighted structural brain images were acquired from 23 lithium-free euthymic subjects with bipolar I disorder and 19 age-and sex-matched healthy control subjects on a 1.5 T MRI scanner. Scans were processed to provide measures of fractional anisotropy (FA) and mean and radial diffusivity (MD and RD) at each WM voxel, and processed scans were nonlinearly aligned to a customized brain imaging template for statistical group comparisons. Results: Relative to controls, the bipolar group showed widespread regions of lower FA, including the corpus callosum, cortical and thalamic association fibers. MD and RD were abnormally elevated in patients in many of these same regions. Conclusions: Our findings agree with prior reports of WM abnormalities in the corpus callosum and further link a bipolar diagnosis with structural abnormalities of the tapetum, fornix and stria terminalis. Future studies assessing the diagnostic specificity and prognostic implications of these abnormalities would be of interest. (C) 2013 The Authors. Published by Elsevier Inc. Open access under CC BY-NC-SA license. C1 [Barysheva, Marina; Jahanshad, Neda; Foland-Ross, Lara; Thompson, Paul M.] Univ Calif Los Angeles, Sch Med, Dept Neurol, Imaging Genet Ctr,Lab Neuro Imaging, Los Angeles, CA 90024 USA. [Altshuler, Lori L.; Thompson, Paul M.] Univ Calif Los Angeles, Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Altshuler, Lori L.; Thompson, Paul M.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Altshuler, Lori L.] West Los Angeles Healthcare Ctr, VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. RP Thompson, PM (reprint author), Univ Calif Los Angeles, Sch Med, Dept Neurol, Imaging Genet Ctr,Lab Neuro Imaging, Los Angeles, CA 90024 USA. EM thompson@loni.ucla.edu FU National Institute of Mental Health [K24 MH001848, R21 MH075944, R01 MH084955, 5F31MH078556]; National Institute for Biological Imaging and Bioengineering [R01 EB008432, R01 EB007813, P41 RR013642]; National Center for Research Resources [RR12169, RR13642, RR00865]; Brain Mapping Medical Research Organization; Brain Mapping Support Foundation; Pierson-Lovelace Foundation; Ahmanson Foundation; William M. and Linda R. Dietel Philanthropic Fund at the Northern Piedmont Community Foundation; Tamkin Foundation; Jennifer Jones-Simon Foundation; Capital Group Companies Charitable Foundation; Robson Family; Northstar Fund FX This study was funded by the National Institute of Mental Health (K24 MH001848, R21 MH075944, R01 MH084955, 5F31MH078556), the National Institute for Biological Imaging and Bioengineering (R01 EB008432, R01 EB007813, P41 RR013642) and the National Center for Research Resources (RR12169, RR13642, RR00865). For generous support, we thank the Brain Mapping Medical Research Organization, Brain Mapping Support Foundation, Pierson-Lovelace Foundation, The Ahmanson Foundation, William M. and Linda R. Dietel Philanthropic Fund at the Northern Piedmont Community Foundation, Tamkin Foundation, Jennifer Jones-Simon Foundation, Capital Group Companies Charitable Foundation, Robson Family and Northstar Fund. NR 106 TC 28 Z9 29 U1 2 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2013 VL 2 BP 558 EP 568 DI 10.1016/j.nicl.2013.03.016 PG 11 WC Neuroimaging SC Neurosciences & Neurology GA V37LH UT WOS:000209276800061 PM 24179807 ER PT J AU Lindemer, ER Salat, DH Leritz, EC McGlinchey, RE Milberg, WP AF Lindemer, Emily R. Salat, David H. Leritz, Elizabeth C. McGlinchey, Regina E. Milberg, William P. TI Reduced cortical thickness with increased lifetime burden of PTSD in OEF/OIF Veterans and the impact of comorbid TBI SO NEUROIMAGE-CLINICAL LA English DT Article DE Posttraumatic stress disorder; Mild traumatic brain injury; Cortical thickness; Whole-brain analysis; Neuroimaging; Comorbidity ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMATIC BRAIN-INJURY; HUMAN CEREBRAL-CORTEX; MAGNETIC-RESONANCE IMAGES; SURFACE-BASED ANALYSIS; COMBAT-RELATED PTSD; GRAY-MATTER VOLUME; DEFAULT-MODE; FUNCTIONAL CONNECTIVITY; GEOMETRICALLY ACCURATE AB Posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) in military personnel is increasing dramatically following the OEF/OIF conflicts and is associated with alterations to brain structure. The present study examined the relationship between PTSD and cortical thickness, and its possible modification by mTBI, in a 104-subject OEF/OIF veteran cohort ranging in age from 20 to 62 years. For each participant, two T1-weighted scans were averaged to create high-resolution images for calculation of regional cortical thickness. PTSD symptoms were assessed using the Clinician Administered PTSD Scale (CAPS) and scores were derived based on the previous month's symptoms ("current") and a Cumulative Lifetime Burden of PTSD (CLB-P) reflecting the integral of CAPS scores across the lifetime. Mild TBI was diagnosed using the Boston Assessment of TBI-Lifetime (BAT-L). Results demonstrated a clear negative relationship between current PTSD severity and thickness in both postcentral gyri and middle temporal gyri. This relationship was stronger and more extensive when considering lifetime burden (CLB-P), demonstrating the importance of looking at trauma in the context of an individual's lifetime, rather than only at their current symptoms. Finally, interactions with current PTSD only and comorbid current PTSD and mTBI were found in several regions, implying an additive effect of lifetime PTSD and mTBI on cortical thickness. (C) 2013 The Authors. Published by Elsevier Inc. C1 [Lindemer, Emily R.; Salat, David H.; Leritz, Elizabeth C.; McGlinchey, Regina E.; Milberg, William P.] VA Boston Healthcare Syst, Translat Res Ctr TBI & Stress Disorders TRACTS, Boston, MA 02130 USA. [Salat, David H.; Leritz, Elizabeth C.] AA Martinos Ctr Biomed Imaging, Boston, MA USA. [McGlinchey, Regina E.; Milberg, William P.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Leritz, Elizabeth C.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. RP Milberg, WP (reprint author), VA Boston Healthcare Syst, TRACTS GRECC 182,150 S Huntington Ave, Boston, MA 02130 USA. EM William_milberg@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 [B6796-C]; VA Merit Review Award FX This research was support by the Translational Research Center for TBI and Stress Disorders (TRACTS), a VA Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (B6796-C) and VA Merit Review Award to Regina McGlinchey. NR 82 TC 19 Z9 19 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2013 VL 2 BP 601 EP 611 DI 10.1016/j.nicl.2013.04.009 PG 11 WC Neuroimaging SC Neurosciences & Neurology GA V37LH UT WOS:000209276800066 PM 24179811 ER PT J AU Woodward, SH Kuo, JR Schaer, M Kaloupek, DG Eliez, S AF Woodward, Steven H. Kuo, Janice R. Schaer, Marie Kaloupek, Danny G. Eliez, Stephan TI Early adversity and combat exposure interact to influence anterior cingulate cortex volume in combat veterans SO NEUROIMAGE-CLINICAL LA English DT Article DE Posttraumatic stress disorder; Cingulate cortex; Stress, psychological; Combat disorders ID POSTTRAUMATIC-STRESS-DISORDER; DEEP BRAIN-STIMULATION; GRAY-MATTER VOLUME; CHILDHOOD ADVERSITY; HIPPOCAMPAL VOLUME; LIFE EVENTS; PTSD; MALTREATMENT; VARIABILITY; MORPHOMETRY AB Objective: Childhood and combat trauma have been observed to interact to influence amygdala volume in a sample of U. S. military veterans with and without PTSD. This interaction was assessed in a second, functionally-related fear system component, the pregenual and dorsal anterior cingulate cortex, using the same sample and modeling approach. Method: Anterior cingulate cortical tissues (gray + white matter) were manually-delineated in 1.5 T MR images in 87 U.S. military veterans of the Vietnam and Persian Gulf wars. Hierarchical multiple regression modeling was used to assess associations between anterior cingulate volume and the following predictors, trauma prior to age 13, combat exposure, the interaction of early trauma and combat exposure, and PTSD diagnosis. Results: As previously observed in the amygdala, unique variance in anterior cingulate cortical volume was associated with both the diagnosis of PTSD and with the interaction of childhood and combat trauma. The pattern of the latter interaction indicated that veterans with childhood trauma exhibited a significant inverse linear relationship between combat trauma and anterior cingulate volume while those without childhood trauma did not. Such associations were not observed in hippocampal or total cerebral tissue volumes. Conclusions: In the dorsal anterior cingulate cortex, as in the amygdala, early trauma may confer excess sensitivity to later combat trauma. (C) 2013 The Authors. Published by Elsevier Inc. C1 [Woodward, Steven H.] VA Palo Alto Hlth Care Syst, Disseminat & Training Div, Natl Ctr PTSD, Palo Alto, CA 94306 USA. [Kuo, Janice R.] Ryerson Univ, Dept Psychol, Toronto, ON, Canada. [Schaer, Marie; Eliez, Stephan] Univ Geneva, Dept Psychiat, Geneva, Switzerland. [Kaloupek, Danny G.] VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, Boston, MA USA. [Kaloupek, Danny G.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Woodward, SH (reprint author), VA Palo Alto Hlth Care Syst, Disseminat & Training Div, NCPTSD, Natl Ctr PSTD, Palo Alto, CA 94306 USA. EM Steve.woodward@va.gov OI Kaloupek, Danny/0000-0002-0795-593X FU U. S. Army Medical Research and Material Command (DoD) through Institute for Medical Research (VA); National Center of Competence in Research (NCCR) "SYNAPSY The Synaptic Bases of Mental Diseases" - Swiss National Science Foundation [51AU40_125759] FX Funding for this work was supported under a VA/DoD assistance agreement to Drs. Woodward and Kaloupek from the U. S. Army Medical Research and Material Command (DoD) administered through the Institute for Medical Research (VA). Drs. Eliez and Schaer were supported by the National Center of Competence in Research (NCCR) "SYNAPSY The Synaptic Bases of Mental Diseases" financed by the Swiss National Science Foundation (51AU40_125759). We thank the Research Services of the VA Palo Alto and VA Boston Healthcare Systems for their assistance. Important institutional and technical support was also provided by the following individuals: Carla Ambriz, Steven Blank, Thomas J. Brosnan, Eileen Connolly, Michael A. Dove, John E. Drace, Blaise Frederick, Gary E. Gold, Frederick Kanter, Matthew O. Kimble, Catherine J. Kutter, Lorraine P. Leskin, Anil Patwardhan, Rebecca S. Prestel, Susan P. Proctor, Allan L. Reiss, Chris C. Streeter, Perry F. Renshaw, Eric Schmitt, Ann Smith, Patricia Spezia, Wendy K. Stegman, Erica Stone, Kelly Teresi and Rosemond Villafuerte. NR 41 TC 3 Z9 3 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2013 VL 2 BP 670 EP 674 DI 10.1016/j.nicl.2013.04.016 PG 5 WC Neuroimaging SC Neurosciences & Neurology GA V37LH UT WOS:000209276800074 PM 24179818 ER PT B AU Ledoux, WR Hahn, ME AF Ledoux, William R. Hahn, Michael E. BE Winkelstein, BA TI Lower Limb Structure, Function, and Locomotion Biomechanics SO Orthopaedic Biomechanics LA English DT Article; Book Chapter ID HUMAN KNEE-JOINT; FINITE-ELEMENT-ANALYSIS; IN-VIVO KINEMATICS; ANKLE-FOOT COMPLEX; CARTILAGE CONTACT DEFORMATION; 1ST METATARSOPHALANGEAL JOINT; SPATIAL PARALLEL MECHANISMS; INVERSE DYNAMICS SOLUTIONS; PLANTAR FASCIA RELEASE; ROBOTIC GAIT SIMULATOR C1 [Ledoux, William R.; Hahn, Michael E.] VA Puget Sound Hlth Care Syst, Dept Vet Affairs RR&D, Ctr Excellence Limb Loss Prevent & Prosthet Engn, Seattle, WA 98108 USA. [Ledoux, William R.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. [Ledoux, William R.; Hahn, Michael E.] Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA. RP Ledoux, WR (reprint author), VA Puget Sound Hlth Care Syst, Dept Vet Affairs RR&D, Ctr Excellence Limb Loss Prevent & Prosthet Engn, Seattle, WA 98108 USA. NR 157 TC 0 Z9 0 U1 2 U2 2 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-6094-6; 978-1-4398-6093-9 PY 2013 BP 265 EP 297 PG 33 WC Engineering, Biomedical; Orthopedics SC Engineering; Orthopedics GA BD6HY UT WOS:000362228800011 ER PT J AU Zhang, JH AF Zhang, Jianhua TI Autophagy and mitophagy in cellular damage control SO REDOX BIOLOGY LA English DT Review DE Neurodegeneration; Alpha-synuclein; Lysosomes; Fission; Fusion; Reactive species; Cellular bioenergetics; Pharmacological agents AB Autophagy and mitophagy are important cellular processes that are responsible for breaking down cellular contents, preserving energy and safeguarding against accumulation of damaged and aggregated biomolecules. This graphic review gives a broad summary of autophagy and discusses examples where autophagy is important in controlling protein degradation. In addition we highlight how autophagy and mitophagy are involved in the cellular responses to reactive species and mitochondrial dysfunction. The key signaling pathways for mitophagy are described in the context of bioenergetic dysfunction. (C) 2013 The Author. Published by Elsevier B.V. C1 Univ Alabama Birmingham, Dept Pathol, Ctr Free Radical Biol, Birmingham VA Med Ctr, Birmingham, AL 35294 USA. RP Zhang, JH (reprint author), Univ Alabama Birmingham, Dept Pathol, Ctr Free Radical Biol, Birmingham VA Med Ctr, Biomed Res Bldg 2,901 19th St South, Birmingham, AL 35294 USA. EM zhanja@uab.edu OI Zhang, Jianhua/0000-0002-2128-9574 FU VA merit award; [NS064090] FX This work was supported by NS064090 and a VA merit award (JZ). NR 47 TC 36 Z9 38 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2317 J9 REDOX BIOL JI Redox Biol. PY 2013 VL 1 IS 1 BP 19 EP 23 DI 10.1016/j.redox.2012.11.008 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA V38BC UT WOS:000209317900004 PM 23946931 ER PT J AU Konigsberg, M Perez, VI Rios, C Liu, Y Lee, S Shi, Y Van Remmen, H AF Konigsberg, M. Perez, V. I. Rios, C. Liu, Y. Lee, S. Shi, Y. Van Remmen, H. TI Effect of oxygen tension on bioenergetics and proteostasis in young and old myoblast precursor cells SO REDOX BIOLOGY LA English DT Article DE Myoblasts; Mitochondrial respiration; Protein damage; Hypoxia; Oxidative stress AB In the majority of studies using primary cultures of myoblasts, the cells are maintained at ambient oxygen tension (21% O-2), despite the fact that physiological O-2 at the tissue level in vivo is much lower (1-5% O-2). We hypothesized that the cellular response in presence of high oxygen concentration might be particularly important in studies comparing energetic function or oxidative stress in cells isolated from young versus old animals. To test this, we asked whether oxygen tension plays a role in mitochondrial bioenergetics (oxygen consumption, glycolysis and fatty acid oxidation) or oxidative damage to proteins (protein disulfides, carbonyls and aggregates) in myoblast precursor cells (MPCs) isolated from young (3-4 m) and old (29-30 m) C57BL/6 mice. MPCs were grown under physiological (3%) or ambient (21%) O-2 for two weeks prior to exposure to an acute oxidative insult (H2O2). Our results show significantly higher basal mitochondrial respiration in young versus old MPCs, an increase in basal respiration in young MPCs maintained at 3% O-2 compared to cells maintained at 21% O-2, and a shift toward glycolytic metabolism in old MPCs grown at 21% O-2. H2O2 treatment significantly reduced respiration in old MPCs grown at 3% O-2 but did not further repress respiration at 21% O-2 in old MPCs. Oxidative damage to protein was higher in cells maintained at 21% O-2 and increased in response to H2O2 in old MPCs. These data underscore the importance of understanding the effect of ambient oxygen tension in cell culture studies, in particular studies measuring oxidative damage and mitochondrial function. Published by Elsevier By. Open access under CC BY license. C1 [Konigsberg, M.; Perez, V. I.; Rios, C.; Liu, Y.; Lee, S.; Shi, Y.; Van Remmen, H.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Perez, V. I.; Van Remmen, H.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Shi, Y.; Van Remmen, H.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Rios, C.; Van Remmen, H.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Konigsberg, M.] Univ Autonoma Metropolitana Iztapalapa, Mexico City 09340, DF, Mexico. RP Van Remmen, H (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM vanremmen@uthscsa.edu FU Ellison Medical Foundation [AG-NS-0705-10/PEREZ]; NIH [P01 AG20591/VAN REMMEN] FX This work was supported by Ellison Medical Foundation AG-NS-0705-10/PEREZ and by NIH P01 AG20591/VAN REMMEN, MK was a Fulbright and a CONACyT scholar (147827). NR 40 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2317 J9 REDOX BIOL JI Redox Biol. PY 2013 VL 1 IS 1 BP 475 EP 482 DI 10.1016/j.redox.2013.09.004 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA V38BC UT WOS:000209317900066 PM 24191243 ER PT J AU Luoh, SW Ramsey, B Newell, AH Troxell, M Hu, Z Chin, K Spellman, P Olson, S Keenan, E AF Luoh, Shiuh-Wen Ramsey, Betsy Newell, Amy Hanlon Troxell, Megan Hu, Zhi Chin, Koei Spellman, Paul Olson, Susan Keenan, Edward TI HER-2 gene amplification in human breast cancer without concurrent HER-2 over-expression SO SPRINGERPLUS LA English DT Article AB Background: Testing for human epidermal growth factor receptor-2 (HER-2) in breast cancer is performed by either immunohistochemistry (IHC) or in situ hybridization (ISH). The growth factor receptor-bound protein-7 (GRB7) gene is in close proximity to HER-2 on chromosome 17q11-12 and codes a signal transduction molecule shown to be an independent adverse marker in breast cancer. Methods: HER-2 and GRB7 protein expression from 613 frozen breast tumors was determined by Western analysis. HER-2 protein results were confirmed with IHC. Commercial HER-2 FISH was performed on a subset of tumors with multi-probe FISH used to assess the extent of HER-2 gene amplification. mRNA expression was determined by Multi-plex RT-PCR. Results: Seven tumors with GRB7 protein over-expression scored HER-2 FISH amplified but had no HER-2 protein over-expression. Four of the 7 tumors showed elevated GRB7 but not HER-2 mRNA over-expression. The breast cancer cell line HCC3153 did not over-express HER-2 protein but showed HER-2 FISH amplification of a limited segment around the HER-2 gene. Ten breast cancer tumors from the TCGA database had gene copy number increases around HER-2 without HER-2 mRNA or protein over-expression. Conclusions: A subset of human breast cancers that test positive with FISH for HER-2 gene amplification do not over-express HER-2 protein. One mechanism for this discordance is the incomplete amplification of the smallest HER-2 region of chromosome 17q11-12, which includes GRB7. HER-2 gene amplification without protein over-expression is clinically significant because patients with such tumors are unlikely to benefit from HER-2 targeted therapy. C1 [Luoh, Shiuh-Wen] Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, Portland, OR 97239 USA. [Luoh, Shiuh-Wen] Portland VA Med Ctr, Portland, OR 97239 USA. [Ramsey, Betsy] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. [Newell, Amy Hanlon; Spellman, Paul; Olson, Susan] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97239 USA. [Troxell, Megan] Oregon Hlth & Sci Univ, Dept Anat Pathol, Portland, OR 97239 USA. [Hu, Zhi; Chin, Koei] Oregon Hlth & Sci Univ, OHSU Dept Biomed Engn, Portland, OR 97239 USA. [Hu, Zhi; Chin, Koei] Oregon Hlth & Sci Univ, Ctr Spatial Syst Biomed, Portland, OR 97239 USA. [Luoh, Shiuh-Wen; Ramsey, Betsy; Troxell, Megan; Olson, Susan; Keenan, Edward] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA. RP Luoh, SW (reprint author), Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, 3181 SW Sam Jackson Pk Rd,MC L586, Portland, OR 97239 USA. EM luohs@ohsu.edu FU Portland VA Research Foundation; OHSU Foundation FX This work is supported in part by Portland VA Research Foundation and OHSU Foundation. NR 45 TC 3 Z9 4 U1 1 U2 2 PU SPRINGER INTERNATIONAL PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 2193-1801 J9 SPRINGERPLUS JI SpringerPlus PY 2013 VL 2 AR 386 DI 10.1186/2193-1801-2-386 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V40FR UT WOS:000209465000183 PM 24102037 ER PT J AU Meisel, JL Economy, KE Calvillo, KZ Schapira, L Tung, NM Gelber, S Kereakoglow, S Partridge, AH Mayer, EL AF Meisel, Jane L. Economy, Katherine E. Calvillo, Katherina Zabicki Schapira, Lydia Tung, Nadine M. Gelber, Shari Kereakoglow, Sandra Partridge, Ann H. Mayer, Erica L. TI Contemporary multidisciplinary treatment of pregnancy-associated breast cancer SO SPRINGERPLUS LA English DT Article DE Pregnancy; Breast cancer; Chemotherapy; Fetal outcomes; Multidisciplinary care AB Breast cancer diagnosed during pregnancy poses unique challenges. Application of standard treatment algorithms is limited by lack of level I evidence from randomized trials. This study describes contemporary multidisciplinary treatment of pregnancy-associated breast cancer (PABC) in an academic setting and explores early maternal and fetal outcomes. A search of the Dana-Farber/Harvard Cancer Center clinical databases was performed to identify PABC cases. Sociodemographic, disease, pregnancy, and treatment information, as well as data on short-term maternal and fetal outcomes, were collected through retrospective chart review. 74 patients were identified, the majority with early-stage breast cancer. Most (73.5%) underwent surgical resection during pregnancy, including 40% with sentinel lymph node biopsy and 32% with immediate reconstruction. A total of 36 patients received anthracycline-based chemotherapy during pregnancy; of those, almost 20% were on a dose-dense schedule and 8.3% also received paclitaxel. 68 patients delivered liveborn infants; over half were delivered preterm (< 37 weeks), most scheduled to allow further maternal cancer therapy. For the infants with available data, all had normal Apgar scores and over 90% had birth weight > 10th percentile. The rate of fetal malformations (4.4%) was not different than expected population rate. Within a multidisciplinary academic setting, PABC treatment followed contemporary algorithms without apparent increase in maternal or fetal adverse outcomes. A considerable number of preterm deliveries were observed, the majority planned to facilitate cancer therapy. Continued attention to maternal and fetal outcomes after PABC is required to determine the benefit of this delivery strategy. C1 [Meisel, Jane L.; Economy, Katherine E.; Calvillo, Katherina Zabicki; Partridge, Ann H.; Mayer, Erica L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Schapira, Lydia] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tung, Nadine M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Calvillo, Katherina Zabicki; Gelber, Shari; Kereakoglow, Sandra; Partridge, Ann H.; Mayer, Erica L.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Mayer, EL (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM emayer@partners.org NR 40 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER INTERNATIONAL PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 2193-1801 J9 SPRINGERPLUS JI SpringerPlus PY 2013 VL 2 AR 297 DI 10.1186/2193-1801-2-297 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V40FR UT WOS:000209465000095 PM 23888269 ER PT J AU Thanabalasundaram, G Hernandez-Duran, S Leslie-Mazwi, T Ogilvy, CS AF Thanabalasundaram, Gopiga Hernandez-Duran, Silvia Leslie-Mazwi, Thabele Ogilvy, Christopher S. TI Cortical non-aneurysmal subarachnoid hemorrhage post-carotid endarterectomy: a case report and literature review SO SPRINGERPLUS LA English DT Article DE Non-aneurysmal subarachnoid hemorrhage; Carotid endarterectomy; Carotid stenosis; Reperfusion injury AB Cerebral hyperperfusion syndrome is a well-recognized and potentially fatal complication of carotid revascularization. However, the occurrence of non-aneurysmal subarachnoid hemorrhage as a manifestation of cerebral hyperperfusion syndrome post-carotid endarterectomy is uncommon. We report a case of a patient who presented with headache following carotid endarterectomy for a critically occluded common carotid artery. This progressed to deteriorating consciousness and seizures. Investigations revealed a left cortical non-aneurysmal subarachnoid hemorrhage. Non-aneurysmal subarachnoid hemorrhage is a rare post-operative complication of carotid endarterectomy. Immediate management with aggressive blood pressure control is key to prevent permanent neurological deficits. Cerebral hyperperfusion syndrome (CHS) after carotid revascularization procedures is an uncommon and potentially fatal complication. Pathophysiologically it is attributed to impaired autoregulatory mechanisms and results in disruption of cerebral hemodynamics with increased regional cerebral blood flow (Cardiol Rev 20: 84-89, 2012; J Vasc Surg 49: 1060-1068, 2009). The condition is characterized by throbbing ipsilateral frontotemporal or periorbital headache. Other symptoms include vomiting, confusion, macular edema, focal motor seizures with frequent secondary generalization, focal neurological deficits, and intraparenchymal or subarachnoid hemorrhage (SAH) (Lancet Neurol 4: 877-888, 2005). The incidence of CHS varies from 0.2% to 18.9% after carotid endarterectomy (CEA), with a typical reported incidence of less than 3% in larger studies (Cardiol Rev 20: 84-89, 2012; Neurosurg 107: 1130-1136, 2007). Uncontrolled hypertension, an arterially isolated cerebral hemisphere, and contralateral carotid occlusion are the main risk factors (Lancet Neurol 4: 877-888, 2005; J Neurol Neurosurg Psychiatry 83: 543-550, 2012). We present a case of non-aneurysmal SAH after CEA, with focus on its presentation, risk factors, and management. C1 [Thanabalasundaram, Gopiga; Hernandez-Duran, Silvia; Ogilvy, Christopher S.] Harvard Univ, Sch Med, Massachussetts Gen Hosp, Neurosurg Serv, Boston, MA 02138 USA. [Thanabalasundaram, Gopiga; Hernandez-Duran, Silvia; Leslie-Mazwi, Thabele; Ogilvy, Christopher S.] Massachusetts Gen Hosp, Neuroendovasc Serv, Boston, MA 02114 USA. [Thanabalasundaram, Gopiga] UCL, Sch Med, London WC1E 6BT, England. [Hernandez-Duran, Silvia] Univ Costa Rica, San Jose, Costa Rica. RP Thanabalasundaram, G (reprint author), Harvard Univ, Sch Med, Massachussetts Gen Hosp, Neurosurg Serv, 55 Fruit St,Wang 745, Boston, MA 02138 USA. EM gopithana@gmail.com NR 13 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INTERNATIONAL PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 2193-1801 J9 SPRINGERPLUS JI SpringerPlus PY 2013 VL 2 AR 571 DI 10.1186/2193-1801-2-571 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V40FS UT WOS:000209465100143 PM 24255864 ER PT B AU Gonzalez-Perez, RR Rueda, BR AF Gonzalez-Perez, Ruben R. Rueda, Bo R. BE GonzalezPerez, RR Rueda, BR TI Tumor Angiogenesis Regulators Preface SO TUMOR ANGIOGENESIS REGULATORS LA English DT Editorial Material; Book Chapter C1 [Gonzalez-Perez, Ruben R.] Morehouse Sch Med, Dept Microbiol Biochem & Immunol, Atlanta, GA 30310 USA. [Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. [Rueda, Bo R.] Harvard Med Sch, Obstet Gynecol & Reprod Biol, Boston, MA USA. RP Gonzalez-Perez, RR (reprint author), Morehouse Sch Med, Dept Microbiol Biochem & Immunol, Atlanta, GA 30310 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4665-8098-5; 978-1-4665-8097-8 PY 2013 BP V EP VI PG 2 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BF7YR UT WOS:000384589000001 ER PT B AU Growdon, W Foster, R Bradford, L Rueda, BR AF Growdon, Whitfield Foster, Rosemary Bradford, Leslie Rueda, Bo R. BE GonzalezPerez, RR Rueda, BR TI Angiogenesis in Gynecologic Cancers The Promise of Innovative Therapies SO TUMOR ANGIOGENESIS REGULATORS LA English DT Article; Book Chapter DE Gynecologic Cancer; Angiogenesis; Targeted Therapy ID ENDOTHELIAL GROWTH-FACTOR; SQUAMOUS-CELL CARCINOMA; EPITHELIAL OVARIAN-CANCER; FALLOPIAN-TUBE CANCER; PHASE-II TRIAL; CERVICAL INTRAEPITHELIAL NEOPLASIA; METASTATIC COLORECTAL-CANCER; BEVACIZUMAB PLUS IRINOTECAN; TUMOR MICROVESSEL DENSITY; PRIMARY PERITONEAL CANCER AB Angiogenesis is a fundamental process that tumors require to develop, grow and allow metastatic cells to successfully implant and form new tumor. While treatable, gynecologic cancers pose many challenges in the upfront and particularly recurrent setting. Scientific insight into the pathogenesis of these tumors is important for setting. Scientific insight into the pathogenesis of these tumors is important for improving outcomes related to current therapeutic strategies. To date, preclinical investigation has demonstrated that cancers of the ovary, uterus and cervix manifest heightened activation of specific pathways that promote the formation of new vasculature. These findings have provided scientific rationale for the numerous clinical trials that have tested diverse therapies that inhibit signaling pathways contributing to angiogenesis in gynecologic cancers. While it is unclear how anti-angiogenic therapy will be used in the treatment of ovarian, uterine and cervical cancer, recent evidence supports its use in subsets of patients with these malignancies, particularly in the recurrent setting. Defining a molecular signature associated with response to specific anti-angiogenic therapies will be crucial to the success of this approach in the future. C1 [Growdon, Whitfield; Foster, Rosemary; Bradford, Leslie; Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Dept Obstet & Gynecol, Boston, MA USA. RP Rueda, BR (reprint author), Massachusetts Gen Hosp, Thier 901A,55 Fruit St, Boston, MA 02114 USA. EM brueda@partners.org NR 141 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4665-8098-5; 978-1-4665-8097-8 PY 2013 BP 357 EP 385 PG 29 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BF7YR UT WOS:000384589000011 ER PT B AU Incio, J Soares, R AF Incio, Joao Soares, Raquel BE GonzalezPerez, RR Rueda, BR TI Obesity, Diabetes and Metabolic Syndrome Impact on Tumor Angiogenesis SO TUMOR ANGIOGENESIS REGULATORS LA English DT Article; Book Chapter DE Obesity; metabolic syndrome; diabetes; angiogenesis; adipokines; cancer; inflammation ID VISCERAL ADIPOSE-TISSUE; FACTOR-I RECEPTOR; BODY-MASS INDEX; BREAST-CANCER; ENDOTHELIAL-CELLS; COLON-CANCER; INSULIN-RESISTANCE; RETINAL NEOVASCULARIZATION; STIMULATES ANGIOGENESIS; CHRONIC INFLAMMATION AB In the last few decades, the world has been challenged with a cluster of metabolic disturbances that induce susceptibility to cancer and cardiovascular diseases, two major pathological conditions that contributes to the increasing morbidity and mortality rates in the 21st century. Among these disturbances are obesity, diabetes and metabolic syndrome. Metabolic syndrome co-aggregates established cardiovascular risk factors, including insulin resistance, hypertension, dislipidemia and central obesity itself. Interestingly, adipose tissue is no longer considered a merely energy storage tissue. Rather, the release of distinct hormones, as well as of inflammatory cytokines, rendered it an established endocrine and inflammatory organ with a potential to modulate angiogenesis. Accordingly, obesity, diabetes and metabolic syndrome are characterized by distinct features that enhance angiogenesis, such as hypoxia, low grade inflammation, oxidative stress, hormone imbalance or hyperglycemia, which are also key players in cancer development and progression. Corroborating these findings, metabolic disorders have been associated with increased incidence and poor outcome of several types of neoplasia, including the highly prevalent breast, prostate and colorectal cancer. Therefore, angiogenesis is very likely a key player in this association between these metabolic conditions and cancer. Given the epidemic character of obesity, diabetes and metabolic syndrome, which are already considered to be major public health threats, and elucidating the angiogenic mechanisms implicated in these metabolic disorders predisposing and promoting cancer, becomes of paramount importance. The present chapter focuses on the pro-angiogenic environment that is primarily developed in these metabolic disorders, and its relevance to tumor progression. C1 [Incio, Joao] Harvard Med Sch, Massachusetts Gen Hosp, Edwin L Steele Lab Tumor Biol, Dept Radiat Oncol, Boston, MA 02114 USA. [Soares, Raquel] Univ Porto, Dept Biochem FCT U38, Fac Med, P-4200319 Oporto, Portugal. RP Soares, R (reprint author), Univ Porto, Dept Biochem FCT U38, Fac Med, P-4200319 Oporto, Portugal. EM jincio@steele.mgh.harvard.edu; raqsoa@med.up.pt NR 98 TC 4 Z9 4 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4665-8098-5; 978-1-4665-8097-8 PY 2013 BP 411 EP 431 PG 21 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BF7YR UT WOS:000384589000013 ER PT S AU Bartley, J Camargo, CA AF Bartley, Jim Camargo, Carlos A., Jr. BE Gombart, AF TI Vitamin D and Infection SO VITAMIN D: OXIDATIVE STRESS, IMMUNITY, AND AGING SE Oxidative Stress and Disease LA English DT Article; Book Chapter ID D-RECEPTOR GENE; RESPIRATORY-TRACT INFECTION; RANDOMIZED-CONTROLLED-TRIAL; 25-HYDROXYVITAMIN D LEVELS; ANTIMICROBIAL PEPTIDE CATHELICIDIN; HELICOBACTER-PYLORI INFECTION; NUTRITION EXAMINATION SURVEY; PLACEBO-CONTROLLED TRIAL; 3RD NATIONAL-HEALTH; YOUNG FINNISH MEN C1 [Bartley, Jim] Univ Auckland, Dept Surg, Auckland, New Zealand. [Camargo, Carlos A., Jr.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA USA. RP Bartley, J (reprint author), Univ Auckland, Dept Surg, Auckland, New Zealand. NR 230 TC 1 Z9 1 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA SN 2155-0255 BN 978-1-4398-5021-3; 978-1-4398-5020-6 J9 OXIDAT STRESS DIS PY 2013 VL 31 BP 323 EP 348 PG 26 WC Biochemistry & Molecular Biology; Immunology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Immunology; Nutrition & Dietetics GA BF0KW UT WOS:000379007600015 ER PT J AU Frakt, AB Carroll, AE AF Frakt, Austin B. Carroll, Aaron E. TI The Quality Imperative A Commentary on the U.S. Healthcare System SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; INNOVATION; INSURANCE; THERAPY C1 [Frakt, Austin B.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02130 USA. [Frakt, Austin B.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Dept Vet Affairs, Boston, MA 02130 USA. [Carroll, Aaron E.] Indiana Univ Sch Med, Ctr Hlth Policy & Professionalism Res, Indianapolis, IN USA. RP Frakt, AB (reprint author), Boston Univ, Sch Med, Dept Psychiat, 150 S Huntington Ave, Boston, MA 02130 USA. EM frakt@bu.edu NR 29 TC 4 Z9 4 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JAN PY 2013 VL 44 IS 1 SU 1 BP S22 EP S26 DI 10.1016/j.amepre.2012.09.010 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 044QF UT WOS:000311636100006 PM 23195161 ER PT J AU George, MS Taylor, JJ Short, EB AF George, Mark S. Taylor, Joseph J. Short, E. Baron TI The expanding evidence base for rTMS treatment of depression SO CURRENT OPINION IN PSYCHIATRY LA English DT Review DE depression; magnetic; stimulation; transcranial magnetic stimulation; transcranial; treatment ID TRANSCRANIAL MAGNETIC STIMULATION; HUMAN MOTOR CORTEX; TREATMENT-RESISTANT DEPRESSION; LEFT PREFRONTAL RTMS; DEEP BRAIN-REGIONS; MAJOR DEPRESSION; CHRONIC PAIN; TMS; EFFICACY; COIL AB Purpose of review Daily left prefrontal transcranial magnetic stimulation (TMS) for several weeks was first proposed as an acute treatment for depression in the early 1990s, and was Food and Drug Administration (FDA) approved in 2008. In the past year, several important studies have been published that extend our understanding of this novel treatment approach. Recent findings The first round of multisite clinical trials with TMS addressed whether prefrontal rTMS has efficacy and were conducted in carefully selected depressed patients who were antidepressant medication free. Several more recent studies assess the clinical effectiveness of TMS and report that about 35-40% of real-world patients who are commonly taking adjunctive antidepressants reach remission with a modest side effect profile. There are also new studies examining the durability of the TMS-induced antidepressant effect. Fifty-eight percent of TMS remitters remain remitted at 3-month follow-up. Summary These recent studies suggest that daily left prefrontal TMS over several weeks as a treatment for depression not only appears to have efficacy in rigorous randomized controlled trials, but is effective in real-world settings, with remission in 30-40% of patients. The TMS antidepressant effect, once achieved, appears to be as durable as with other antidepressant medications or interventions. Much more research is needed, particularly with issues such as the TMS coil location, stimulation intensity and frequency, and dosing strategy. C1 [George, Mark S.] Med Univ S Carolina, Dept Psychiat, IOP, Brain Stimulat Lab, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP George, MS (reprint author), Med Univ S Carolina, Dept Psychiat, IOP, Brain Stimulat Lab, 502 North,67 President St, Charleston, SC 29425 USA. EM georgem@musc.edu FU NIH; DOD; VA; NARSAD; Brainsway; Cervel (Neostim); Neosync; Neuronetics; Neuropace; MECTA; St Jude FX The authors' work with brain stimulation treatments has been supported over the past 5 years in part by research grants from NIH, DOD, VA, and NARSAD. The BSL has also received grant funding from Brainsway, Cervel (Neostim), Neosync, Neuronetics, Neuropace, MECTA and St Jude. NR 79 TC 64 Z9 65 U1 7 U2 41 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD JAN PY 2013 VL 26 IS 1 BP 13 EP 18 DI 10.1097/YCO.0b013e32835ab46d PG 6 WC Psychiatry SC Psychiatry GA 048EL UT WOS:000311892900004 PM 23154644 ER PT J AU Unizony, S Stone, JH Stone, JR AF Unizony, Sebastian Stone, John H. Stone, James R. TI New treatment strategies in large-vessel vasculitis SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE aortitis; giant cell arteritis; IgG4-related disease; leflunomide; rituximab; Takayasu arteritis; tocilizumab ID GIANT-CELL ARTERITIS; REFRACTORY TAKAYASUS-ARTERITIS; REGULATORY B-CELLS; ANTI-TNF-ALPHA; TERM-FOLLOW-UP; INTERLEUKIN-6 BLOCKADE; AUTOIMMUNE-DISEASE; DEPLETION THERAPY; RESCUE TREATMENT; T-CELLS AB Purpose of review Recent advancements in the understanding of the pathogenesis of large-vessel vasculitis may broaden our currently limited therapeutic possibilities. This review summarizes the available evidence for new treatment strategies in this spectrum of diseases. Recent findings Interleukin (IL) 6 appears to be an important mediator of the pathology in large-vessel vasculitis. IL-6 is upregulated in inflamed arteries of patients with giant cell arteritis and Takayasu arteritis, and serum levels of this cytokine mirror disease activity. Encouraging preliminary results have been obtained with the IL-6 receptor (IL-6R) antagonist tocilizumab for the treatment of large-vessel vasculitides, including both giant cell arteritis and Takayasu arteritis, and the aortitis of Cogan syndrome and relapsing polychondritis. A small number of patients with Takayasu arteritis and IgG4-related aortitis have also been successfully treated with the B-cell depleting agent rituximab, and some patients with refractory Takayasu arteritis have responded to the immunomodulator leflunomide. Summary The possibility of biologic therapy in large vessel vasculitis has emerged. At this time, better delineation of the immunopathogenic mechanisms of this spectrum of diseases and prospective randomized clinical trials are required to move the field forward and decrease the cumulative glucocorticoid toxicity seen in these disorders. C1 [Stone, James R.] Massachusetts Gen Hosp, Dept Pathol, Ctr Syst Biol, Boston, MA 02114 USA. [Stone, James R.] Harvard Univ, Sch Med, Boston, MA USA. [Unizony, Sebastian; Stone, John H.] Massachusetts Gen Hosp, Rheumatol Unit, Div Rheumatol Allergy & Immunol, Dept Med, Boston, MA 02114 USA. RP Stone, JR (reprint author), Massachusetts Gen Hosp, Dept Pathol, Ctr Syst Biol, Simches Res Bldg,Room 8236,185 Cambridge St CPZN, Boston, MA 02114 USA. EM jrstone@partners.org FU Massachusetts General Hospital; Merck; GlaxoSmithKline; Roche; Genentech FX This work was supported by Massachusetts General Hospital.; Dr James R. has received fees for consulting from Merck and fees for consulting and expert testimony from GlaxoSmithKline. Dr John H. Stone is the Principal Investigator of a Roche-funded trial of tocilizumab in giant cell arteritis and has received consulting fees on study design from Roche for that trial. Dr John H. Stone has also received research grants from Genentech for the study of IgG4-related disease and the utility of rituximab in treating that condition. NR 57 TC 34 Z9 36 U1 0 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI Curr. Opin. Rheumatol. PD JAN PY 2013 VL 25 IS 1 BP 3 EP 9 DI 10.1097/BOR.0b013e32835b133a PG 7 WC Rheumatology SC Rheumatology GA 048WT UT WOS:000311944600003 PM 23114585 ER PT J AU Tschumperlin, DJ Liu, F Tager, AM AF Tschumperlin, Daniel J. Liu, Fei Tager, Andrew M. TI Biomechanical regulation of mesenchymal cell function SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE extracellular matrix; fibrosis; mechanotransduction; stiffness ID ACTIVATES LATENT TGF-BETA-1; HYPERTROPHIC SCAR FORMATION; FOCAL ADHESION KINASE; TGF-BETA; HIPPO PATHWAY; ACTIN DYNAMICS; MYOFIBROBLAST TRANSITION; TRANSCRIPTION FACTOR; MECHANICAL FORCE; MATRIX STIFFNESS AB Purpose of review Cells of mesenchymal origin are strongly influenced by their biomechanical environment. They also help to shape tissue architecture and reciprocally influence tissue mechanical environments through their capacity to deposit, remodel, and resorb extracellular matrix and to promote tissue vascularization. Although mechanical regulation of cell function and tissue remodeling has long been appreciated in other contexts, the purpose of this review is to highlight the increasing appreciation of its importance in fibrosis and hypertrophic scarring. Recent findings Experiments in both animal and cellular model systems have demonstrated pivotal roles for the biomechanical environment in regulating myofibroblast differentiation and contraction, endothelial barrier function and angiogenesis, and mesenchymal stem cell fate decisions. Through these studies, a better understanding of the molecular mechanisms transducing the biomechanical environment is emerging, with prominent and interacting roles recently identified for key network components including transforming growth factor-beta/SMAD, focal adhesion kinase, MRTFs, Wnt/beta-catenin and YAP/TAZ signaling pathways. Summary Progress in understanding biomechanical regulation of mesenchymal cell function is leading to novel approaches for improving clinical outcomes in fibrotic diseases and wound healing. These approaches include interventions aimed at modifying the tissue biomechanical environment, and efforts to target mesenchymal cell activation by, and reciprocal interactions with, the mechanical environment. C1 [Tschumperlin, Daniel J.; Liu, Fei] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Tager, Andrew M.] Harvard Univ, Sch Med, Pulm & Crit Care Unit, Charlestown, MA USA. [Tager, Andrew M.] Harvard Univ, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol,Sch Med, Charlestown, MA USA. RP Tschumperlin, DJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM DTSCHUMP@hsph.harvard.edu FU National Institutes of Health [R01-HL092961, R01-HL095732, R01-HL108975] FX The support for this study was provided by National Institutes of Health Grants R01-HL092961, R01-HL095732 and R01-HL108975. NR 72 TC 20 Z9 21 U1 2 U2 88 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI Curr. Opin. Rheumatol. PD JAN PY 2013 VL 25 IS 1 BP 92 EP 100 DI 10.1097/BOR.0b013e32835b13cd PG 9 WC Rheumatology SC Rheumatology GA 048WT UT WOS:000311944600016 PM 23114589 ER PT J AU Moore, CI Crosier, E Greve, DN Savoy, R Merzenich, MM Dale, AM AF Moore, Christopher I. Crosier, Emilie Greve, Douglas N. Savoy, Robert Merzenich, Michael M. Dale, Anders M. TI Neocortical Correlates of Vibrotactile Detection in Humans SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID PRIMARY SOMATOSENSORY CORTEX; POSITRON EMISSION TOMOGRAPHY; TACTILE DISCRIMINATION TASK; FUNCTIONAL MRI; LATERAL SULCUS; SOMATOTOPIC ORGANIZATION; DISCHARGE PROPERTIES; MACAQUE MONKEYS; HUMAN BRAIN; BLOOD-FLOW AB This study examined the cortical representation of vibrotactile detection in humans using event-related fMRI paired with psychophysics. Suprathreshold vibrotactile stimulation activated several areas, including primary (SI) and second somatosensory cortices (SII/PV). For threshold-level stimuli, poststimulus activity in contralateral and ipsilateral SII/PV was the best correlate of detection success. In these areas, evoked signals on hit trials were significantly greater than on missed trials in all participants, and the relative activity level across stimulation amplitudes matched perceptual performance. Activity in the anterior insula and superior temporal gyrus also correlated with hits and misses, suggesting that a "ventral stream" of somatosensory representations may play a crucial role in detection. In contrast, poststimulus activity in Area SI was not well correlated with perception and showed an overall negative response profile for threshold-level stimulation. A different correlate of detection success was, however, observed in SI. Activity in this representation immediately before stimulus onset predicted performance, a finding that was unique to SI. These findings emphasize the potential role of SII/PV in detection, the importance of state dynamics in SI for perception, and the possibility that changes in the temporal and spatial pattern of SI activity may be essential to the optimal representation of threshold-level stimuli for detection. C1 [Moore, Christopher I.] Brown Univ, Dept Neurosci, Pawtucket, RI 02860 USA. [Greve, Douglas N.; Savoy, Robert; Dale, Anders M.] Massachusetts Gen Hosp, Martinos Ctr, Boston, MA 02114 USA. [Merzenich, Michael M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Dale, Anders M.] Univ Calif San Diego, San Diego, CA 92103 USA. RP Moore, CI (reprint author), Brown Univ, Dept Neurosci, 165 Meeting St,Box G-LN, Pawtucket, RI 02860 USA. EM Christopher_Moore@brown.edu NR 78 TC 3 Z9 3 U1 1 U2 11 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD JAN PY 2013 VL 25 IS 1 BP 49 EP 61 PG 13 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 048TG UT WOS:000311935300008 PM 23198890 ER PT J AU Spreng, RN Sepulcre, J Turner, GR Stevens, WD Schacter, DL AF Spreng, R. Nathan Sepulcre, Jorge Turner, Gary R. Stevens, W. Dale Schacter, Daniel L. TI Intrinsic Architecture Underlying the Relations among the Default, Dorsal Attention, and Frontoparietal Control Networks of the Human Brain SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID RESTING HUMAN BRAIN; GLOBAL SIGNAL REGRESSION; PARTIAL LEAST-SQUARES; HUMAN CEREBRAL-CORTEX; FUNCTIONAL CONNECTIVITY; MODE NETWORK; STRUCTURAL CONNECTIVITY; MODULAR ORGANIZATION; COGNITIVE CONTROL; CINGULATE CORTEX AB Human cognition is increasingly characterized as an emergent property of interactions among distributed, functionally specialized brain networks. We recently demonstrated that the antagonistic "default" and "dorsal attention" networks-subserving internally and externally directed cognition, respectively-are modulated by a third "frontoparietal control" network that flexibly couples with either network depending on task domain. However, little is known about the intrinsic functional architecture underlying this relationship. We used graph theory to analyze network properties of intrinsic functional connectivity within and between these three large-scale networks. Task-based activation from three independent studies were used to identify reliable brain regions ("nodes") of each network. We then examined pairwise connections ("edges") between nodes, as defined by resting-state functional connectivity MRI. Importantly, we used a novel bootstrap resampling procedure to determine the reliability of graph edges. Furthermore, we examined both full and partial correlations. As predicted, there was a higher degree of integration within each network than between networks. Critically, whereas the default and dorsal attention networks shared little positive connectivity with one another, the frontoparietal control network showed a high degree of between-network interconnectivity with each of these networks. Furthermore, we identified nodes within the frontoparietal control network of three different types-default-aligned, dorsal attention-aligned, and dual-aligned-that we propose play dissociable roles in mediating internetwork communication. The results provide evidence consistent with the idea that the frontoparietal control network plays a pivotal gate-keeping role in goal-directed cognition, mediating the dynamic balance between default and dorsal attention networks. C1 [Spreng, R. Nathan] Cornell Univ, Dept Human Dev, Ithaca, NY 14853 USA. [Sepulcre, Jorge] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sepulcre, Jorge] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Turner, Gary R.] York Univ, Toronto, ON M3J 2R7, Canada. RP Spreng, RN (reprint author), Cornell Univ, Dept Human Dev, Ithaca, NY 14853 USA. EM nathan.spreng@gmail.com OI Schacter, Daniel/0000-0002-2460-6061; Spreng, R. Nathan/0000-0003-1530-8916 FU NIMH [MH060941] FX We thank Adrian Gilmore, Scott Guerin, and Cliff Robbins for assistance with data collection, Kelly Ann Barnes for assistance with Caret, and the Harvard Center for Brain Science Neuroimaging Core and the Harvard Neuroinformatics Research Group for imaging support. This work was supported by NIMH grant MH060941 to D. L. S. NR 72 TC 147 Z9 150 U1 7 U2 62 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD JAN PY 2013 VL 25 IS 1 BP 74 EP 86 PG 13 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 048TG UT WOS:000311935300010 PM 22905821 ER PT J AU Kachouie, NN Huybers, P Schwartzman, A AF Kachouie, Nezamoddin N. Huybers, Peter Schwartzman, Armin TI Localization of mountain glacier termini in Landsat multi-spectral images SO PATTERN RECOGNITION LETTERS LA English DT Article DE Glacier terminus location; Satellite imagery; Landsat multispecrral images; Inflection point; Polynomial regression; Correlated noise ID CHANGE-POINTS; REGRESSION AB This paper addresses the quantification of glacier retreat through remote sensing. Specifically, we use multi-spectral Landsat satellite images for the estimation of glacier termini locations. Different frequency bands-including visual, infrared, thermal, and processed bands-are examined with respect to their utility in identifying the location of glacier termini and the associated standard error across several scenes. The methodology is to extract an intensity profile along the glacier path from the spatially registered Landsat imagery such that the complexity of the problem is reduced from 2D (image intensity) to 1D (glacier profile intensity). Local polynomial regression is then used to smooth the 1D glacier intensity profile, where the underlying function is assumed to be corrupted with correlated noise. The glacier terminus is then detected by locating an inflection point in the smoothed glacier profile, where a constrained bandwidth selection method is introduced to ensure a single inflection point along the glacier path. Using our method with thermal band B62 and a standard processed band called normalized difference snow index (NOS!) often permits for separating ice from soil but does not lead to a consistent identification of termini location, relative to ground based observations. We therefore introduce a new processed band that combines B62 and NDSI, termed normalized difference thermal snow index (NDTSI). Applying our method along with NDTSI to multiple frames from the Franz Josef, Corner, Rhone, and Nigardsbreen glaciers indicates an ability to accurately and robustly identify the position of glacier termini, though confirmation of skill awaits application to a larger population of observations. (C) 2012 Elsevier B.V. All rights reserved. C1 [Kachouie, Nezamoddin N.; Schwartzman, Armin] Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. [Kachouie, Nezamoddin N.; Schwartzman, Armin] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA USA. [Huybers, Peter] Harvard Univ, Dept Earth & Planetary Sci, Cambridge, MA 02138 USA. RP Kachouie, NN (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. EM nezam.nk@gmail.com OI Schwartzman, Armin/0000-0001-5335-1611 FU Harvard University Center for the Environment; Harvard School of Public Health Career Incubator Fund FX We thank James Winter and Travis Gerke for helping preprocess the Landsat datasets, as well the Harvard University Center for the Environment and the Harvard School of Public Health Career Incubator Fund for supporting this research. Credit for all Landsat images: US Geological Survey, Department of the Interior/USGS. Credit for glacier ground measurements goes to the following investigators, providers, and sponsoring agencies/institutes:; Franz Josef: T. Chinn, Dr. I. Owens - Dept. of Geography - University of Canterbury, and B. Anderson - Victoria University of Wellington.; Gorner: VAW/scnat agency from 2001 to 2005.; Nigardsbreen: Rekstad Bergen Museum, Norsk Polarinstitutt, Hydrological Dept. - Norwegian water resources and energy directorate (NVE), J. Bernhard - Rekstad Bergen Museum, N. Haakensen - Norwegian water resources and energy directorate (NVE), M. DISCHL - Geographisches Institut UNI Zurich.; Rhone: VAW/scnat agency from 2001 to 2005. NR 23 TC 5 Z9 5 U1 0 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8655 J9 PATTERN RECOGN LETT JI Pattern Recognit. Lett. PD JAN 1 PY 2013 VL 34 IS 1 SI SI BP 94 EP 106 DI 10.1016/j.patrec.2012.07.003 PG 13 WC Computer Science, Artificial Intelligence SC Computer Science GA 048QM UT WOS:000311927600012 ER PT J AU Woods, DC White, YAR Tilly, JL AF Woods, Dori C. White, Yvonne A. R. Tilly, Jonathan L. TI Purification of Oogonial Stem Cells From Adult Mouse and Human Ovaries: An Assessment of the Literature and a View Toward the Future SO REPRODUCTIVE SCIENCES LA English DT Review DE oogenesis; oocyte; ovary; germ cell; stem cell; human ID SPONTANEOUS ACTIVATION; GERMLINE TRANSMISSION; SEMINIFEROUS TUBULES; MICE; TRANSPLANTATION; DROSOPHILA; EGGS; RENEWAL; PROLIFERATION; SPECIFICATION AB Contemporary claims that mitotically active female germ line or oogonial stem cells (OSCs) exist and support oogenesis during postnatal life in mammals have been debated in the field of reproductive biology since March 2004, when a mouse study posed the first serious challenge to the dogma of a fixed pool of oocytes being endowed at birth in more than 50 years. Other studies have since been put forth that further question the validity of this dogma, including the isolation of OSCs from neonatal and adult mouse ovaries by 4 independent groups using multiple strategies. Two of these groups also reported that isolated mouse OSCs, once transplanted back into ovaries of adult female mice, differentiate into fully functional eggs that ovulate, fertilize, and produce healthy embryos and offspring. Arguably, one of the most significant advances in this emerging field was provided by a new research study published this year, which reported the successful isolation and functional characterization of OSCs from ovaries of reproductive age women. Two commentaries on this latest work, one cautiously supportive and one highly skeptical, were published soon afterward. This article evaluates the current literature regarding postnatal oogenesis in mammals and discusses important next steps for future work on OSC biology and function. C1 [Woods, Dori C.; White, Yvonne A. R.; Tilly, Jonathan L.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. [Woods, Dori C.; White, Yvonne A. R.; Tilly, Jonathan L.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Woods, Dori C.; White, Yvonne A. R.; Tilly, Jonathan L.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. RP Tilly, JL (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, THR 901B,55 Fruit St, Boston, MA 02114 USA. EM jtilly@partners.org FU National Institute on Aging [NIH R37-AG012279]; Ruth L. Kirschstein National Research Service Award [NIH F32-AG034809]; Glenn Foundation Award for Research in the Biological Mechanisms of Aging; Henry and Vivian Rosenberg Philanthropic Fund; Sea Breeze Foundation; Vincent Memorial Hospital Research Funds FX The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: Work conducted by the authors discussed herein was supported by a Method to Extend Research in Time (MERIT) Award from the National Institute on Aging (NIH R37-AG012279 to J.L.T.), a Ruth L. Kirschstein National Research Service Award (NIH F32-AG034809 to D.C.W.), a Glenn Foundation Award for Research in the Biological Mechanisms of Aging, the Henry and Vivian Rosenberg Philanthropic Fund, the Sea Breeze Foundation, and Vincent Memorial Hospital Research Funds. NR 46 TC 31 Z9 34 U1 0 U2 41 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD JAN PY 2013 VL 20 IS 1 BP 7 EP 15 DI 10.1177/1933719112462632 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 046YY UT WOS:000311803000001 PM 23024060 ER PT J AU Black, JC Whetstine, JR AF Black, Joshua C. Whetstine, Johnathan R. TI Tipping the lysine methylation balance in disease SO BIOPOLYMERS LA English DT Review DE histone lysine methylation; histone demethylase; histone methyltransferase; chromatin ID HISTONE METHYLTRANSFERASE G9A; BREAST-CANCER; SELECTIVE INHIBITORS; CELL-PROLIFERATION; ELONGATION COMPLEX; DEMETHYLASE GENE; STRUCTURAL BASIS; PROTEIN; LEUKEMIA; EZH2 AB Genomic instability is a major contributing factor to the development and onset of diseases such as cancer. Emerging evidence has demonstrated that maintaining the proper balance of histone lysine methylation is critical to preserve genomic integrity. Genome-wide association studies, gene sequencing, and genome-wide mapping approaches have helped identify mutations, copy number changes, and aberrant gene regulation of lysine methyltransferases (KMTs) and demethylases (KDMs) associated with cancer and cognitive disorders. Structural analysis of KMTs and KDMs has demonstrated the drugability of these enzymes and has led to the discovery of small molecule inhibitors. Use of these inhibitors has allowed better understanding of the biochemical properties of KMTs and KDMs and demonstrated potential for therapeutic use. This review will highlight the methyl modifications, KMTs and KDMs associated with cancer and neurological disorders and how KMT and KDM and the potential for treatment of these conditions with small molecule inhibitors. (C) 2012 Wiley Periodicals, Inc. Biopolymers 99: 127135, 2013. C1 [Whetstine, Johnathan R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02129 USA. RP Whetstine, JR (reprint author), Massachusetts Gen Hosp, Ctr Canc, 13th St, Boston, MA 02129 USA. EM jwhetstine@hms.harvard.edu RI Black, Joshua/Q-2484-2015 FU Ellison Medical Foundation [CA059267, R01GM097360]; Jane Coffin Childs Memorial Fund for Medical Research (Fellowship) FX Contract grant sponsor: Ellison Medical Foundation; Contract grant number: CA059267; Contract grant number: R01GM097360; Contract grant sponsors: The Jane Coffin Childs Memorial Fund for Medical Research (Fellowship) NR 75 TC 14 Z9 15 U1 1 U2 24 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2013 VL 99 IS 2 SI SI BP 127 EP 135 DI 10.1002/bip.22136 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 041RT UT WOS:000311419600004 PM 23175387 ER PT J AU Fass, DM Reis, SA Ghosh, B Hennig, KM Joseph, NF Zhao, WN Nieland, TJF Guan, JS Kuhnle, CEG Tang, WP Barker, DD Mazitschek, R Schreiber, SL Tsai, LH Haggarty, SJ AF Fass, Daniel M. Reis, Surya A. Ghosh, Balaram Hennig, Krista M. Joseph, Nadine F. Zhao, Wen-Ning Nieland, Thomas J. F. Guan, Ji-Song Kuhnle, Chelsea E. Groves Tang, Weiping Barker, Douglas D. Mazitschek, Ralph Schreiber, Stuart L. Tsai, Li-Huei Haggarty, Stephen J. TI Crebinostat: A novel cognitive enhancer that inhibits histone deacetylase activity and modulates chromatin-mediated neuroplasticity SO NEUROPHARMACOLOGY LA English DT Review DE Cognitive enhancer; Histone deacetylases; Epigenetic; Chromatin; Acetylation; CREB ID LONG-TERM-MEMORY; RUBINSTEIN-TAYBI-SYNDROME; TRANSCRIPTIONAL COACTIVATOR CBP; SMALL-MOLECULE INHIBITORS; ELEMENT-BINDING PROTEIN; SYNAPTIC PLASTICITY; ACETYLTRANSFERASE ACTIVITY; GENE-TRANSCRIPTION; NEURITE OUTGROWTH; BETA-CATENIN AB Long-term memory formation is known to be critically dependent upon de novo gene expression in the brain. As a consequence, pharmacological enhancement of the transcriptional processes mediating long-term memory formation provides a potential therapeutic strategy for cognitive disorders involving aberrant neuroplasticity. Here we focus on the identification and characterization of small molecule inhibitors of histone deacetylases (HDACs) as enhancers of CREB (CAMP response element-binding protein)-regulated transcription and modulators of chromatin-mediated neuroplasticity. Using a CREB reporter gene cell line, we screened a library of small molecules structurally related to known HDAC inhibitors leading to the identification of a probe we termed crebinostat that produced robust activation of CREB-mediated transcription. Further characterization of crebinostat revealed its potent inhibition of the deacetylase activity of recombinant class I HDACs 1, 2, 3, and class IIb HDAC6, with weaker inhibition of the class I HDAC8 and no significant inhibition of the class IIa HDACs 4, 5, 7, and 9. In cultured mouse primary neurons, crebinostat potently induced acetylation of both histone H3 and histone H4 as well as enhanced the expression of the CREB target gene Egrl (early growth response 1). Using a hippocampus-dependent, contextual fear conditioning paradigm, mice systemically administered crebinostat for a ten day time period exhibited enhanced memory. To gain insight into the molecular mechanisms of memory enhancement by HDAC inhibitors, whole genome transcriptome profiling of cultured mouse primary neurons treated with crebinostat, combined with bioinformatic analyses of CREB-target genes, was performed revealing a highly connected protein-protein interaction network reflecting modules of genes important to synaptic structure and plasticity. Consistent with these findings, crebinostat treatment increased the density of synapsin-1 punctae along dendrites in cultured neurons. Finally, crebinostat treatment of cultured mouse primary neurons was found to upregulate Bdpf (brain-derived neurotrophic factor) and Gm (granulin) and downregulate Mapt (tau) gene expression-genes implicated in aging-related cognitive decline and cognitive disorders. Taken together, these results demonstrate that crebinostat provides a novel probe to modulate chromatin-mediated neuroplasticity and further suggests that pharmacological optimization of selective of HDAC inhibitors may provide an effective therapeutic approach for human cognitive disorders. This article is part of a Special Issue entitled 'Cognitive Enhancers'. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Fass, Daniel M.; Reis, Surya A.; Ghosh, Balaram; Hennig, Krista M.; Zhao, Wen-Ning; Kuhnle, Chelsea E. Groves; Haggarty, Stephen J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Dept Neurol, Boston, MA 02114 USA. [Fass, Daniel M.; Reis, Surya A.; Ghosh, Balaram; Hennig, Krista M.; Zhao, Wen-Ning; Kuhnle, Chelsea E. Groves; Haggarty, Stephen J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Dept Psychiat, Boston, MA 02114 USA. [Fass, Daniel M.; Reis, Surya A.; Ghosh, Balaram; Hennig, Krista M.; Zhao, Wen-Ning; Nieland, Thomas J. F.; Kuhnle, Chelsea E. Groves; Barker, Douglas D.; Tsai, Li-Huei; Haggarty, Stephen J.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Joseph, Nadine F.; Guan, Ji-Song; Tsai, Li-Huei] MIT, Howard Hughes Med Inst, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. [Tang, Weiping; Schreiber, Stuart L.] Broad Inst Harvard & MIT, Chem Biol Program, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Mazitschek, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. RP Haggarty, SJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Dept Neurol, 185 Cambridge St, Boston, MA 02114 USA. EM haggarty@chgr.mgh.harvard.edu RI Mazitschek, Ralph/E-3741-2013; OI Mazitschek, Ralph/0000-0002-1105-689X; Guan, Ji-Song /0000-0001-5219-0289; Haggarty, Stephen J./0000-0002-7872-168X FU NIH [P50CA086355, R01DA028301, R01DA030321, R01NS051874]; Stanley Medical Research Institute; Howard Hughes Medical Institute; Tau Consortium FX We would like to thank members of the Haggarty and Tsai laboratories, as well as the Stanley Center for Psychiatric Research for their contributions to the critical questions and work ongoing. R. M. is supported through funding from the NIH (P50CA086355). S.J.H. is supported through funding from the NIH (R01DA028301, R01DA030321), the Stanley Medical Research Institute, and the Tau Consortium. L.H.T. is supported through funding from the NIH (R01DA028301, R01NS051874), the Stanley Medical Research Institute, and the Howard Hughes Medical Institute. We would like to acknowledge the contributions of the Broad Institute's Chemical Biology (BCB) Program and Gene Expression Analysis Platform (GAP) in assisting with the CREB reporter gene screen, and performing the Illumina microarray sample labeling, hybridization, and raw data generation, respectively. NR 87 TC 39 Z9 40 U1 2 U2 43 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 EI 1873-7064 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JAN PY 2013 VL 64 SI SI BP 81 EP 96 DI 10.1016/j.neuropharm.2012.06.043 PG 16 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 039MN UT WOS:000311250300011 PM 22771460 ER PT J AU Rabinak, CA Angstadt, M Sripada, CS Abelson, JL Liberzon, I Milad, MR Phan, KL AF Rabinak, Christine A. Angstadt, Mike Sripada, Chandra S. Abelson, James L. Liberzon, Israel Milad, Mohammed R. Phan, K. Luan TI Cannabinoid facilitation of fear extinction memory recall in humans SO NEUROPHARMACOLOGY LA English DT Article DE Cannabinoid; Fear extinction; Cognitive enhancer; Human; Anxiety ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; MEDIAL PREFRONTAL CORTEX; D-CYCLOSERINE; ANXIETY DISORDERS; CONDITIONED FEAR; EXPOSURE THERAPY; ENDOCANNABINOID SYSTEM; CB1 RECEPTORS; SPATIAL MEMORY AB A first-line approach to treat anxiety disorders is exposure-based therapy, which relies on extinction processes such as repeatedly exposing the patient to stimuli (conditioned stimuli; CS) associated with the traumatic, fear-related memory. However, a significant number of patients fail to maintain their gains, partly attributed to the fact that this inhibitory learning and its maintenance is temporary and conditioned fear responses can return. Animal studies have shown that activation of the cannabinoid system during extinction learning enhances fear extinction and its retention. Specifically, CB1 receptor agonists, such as Delta 9-tetrahydrocannibinol (THC), can facilitate extinction recall by preventing recovery of extinguished fear in rats. However, this phenomenon has not been investigated in humans. We conducted a study using a randomized, double-blind, placebo-controlled, between-subjects design, coupling a standard Pavlovian fear extinction paradigm and simultaneous skin conductance response (SCR) recording with an acute pharmacological challenge with oral dronabinol (synthetic THC) or placebo (PBO) 2 h prior to extinction learning in 29 healthy adult volunteers (THC = 14; PBO = 15) and tested extinction retention 24 h after extinction learning. Compared to subjects that received PBO, subjects that received THC showed low SCR to a previously extinguished CS when extinction memory recall was tested 24 h after extinction learning, suggesting that THC prevented the recovery of fear. These results provide the first evidence that pharmacological enhancement of extinction learning is feasible in humans using cannabinoid system modulators, which may thus warrant further development and clinical testing. This article is part of a Special Issue entitled 'Cognitive Enhancers'. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Rabinak, Christine A.; Angstadt, Mike; Sripada, Chandra S.; Abelson, James L.; Liberzon, Israel; Phan, K. Luan] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Liberzon, Israel; Phan, K. Luan] Univ Michigan, Neurosci Program, Ann Arbor, MI 48109 USA. [Milad, Mohammed R.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Milad, Mohammed R.] Harvard Univ, Sch Med, Boston, MA USA. [Phan, K. Luan] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. [Phan, K. Luan] Jesse Brown VA Med Ctr, Mental Hlth Serv Line, Chicago, IL USA. RP Rabinak, CA (reprint author), Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. EM rabinak@med.umich.edu RI Angstadt, Mike/K-2942-2016; OI Angstadt, Mike/0000-0003-4870-7649; Liberzon, Israel/0000-0002-4990-556X FU National Center for Research Resources [UL1RR024986] FX This work was supported by a grant from the National Center for Research Resources (UL1RR024986) to C.A.R. and K.L.P. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. The authors would like to thank Shoko Mori, Maryssa, Lyons, Christina Harrison, and Daanish Chawala for their assistance in recruitment, participant screening, data collection and analyses. NR 96 TC 43 Z9 43 U1 3 U2 31 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 EI 1873-7064 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JAN PY 2013 VL 64 SI SI BP 396 EP 402 DI 10.1016/j.neuropharm.2012.06.063 PG 7 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 039MN UT WOS:000311250300045 PM 22796109 ER PT J AU Nahata, L Cohen, LE Lehmann, LE Yu, RN AF Nahata, Leena Cohen, Laurie E. Lehmann, Leslie E. Yu, Richard N. TI Semen Analysis in Adolescent Cancer Patients Prior to Bone Marrow Transplantation: When is it Too Late for Fertility Preservation? SO PEDIATRIC BLOOD & CANCER LA English DT Article DE bone marrow transplant; fertility; sperm banking ID SPERM BANKING; CHILDHOOD-CANCER; MALE SURVIVORS; CRYOPRESERVATION; INFERTILITY; RISK; MEN; CHEMOTHERAPY; AZOOSPERMIA; EXPERIENCE AB Background. Sperm banking is an effective method of fertility preservation in adolescent boys with cancer but is strikingly underutilized, partly due to inconsistencies in fertility counseling and unclear guidelines regarding who should bank sperm. Patients undergoing bone marrow transplantation (BMT) are of particular interest given the high risk of infertility in this population. Procedure. We reviewed the charts of male cancer patients who underwent BMT at age >= 13 years at the Dana-Farber Cancer Institute (DFCI) from 2003 to 2010 to determine the number of fertility preservation attempts prior to initial treatment and/or BMT, and the outcomes of those sperm banking attempts. Results. Sixty-eight male cancer patients who had a BMT at age >= 13 years at the DFCI from 2003 to 2010 were included in the analysis. Six patients had attempted sperm banking prior to initial therapy. Thirty-three patients attempted to bank prior to BMT; of those, 39% were azoospermic and 15% were oligospermic. Nineteen patients did not attempt to bank, and in 13 patients the decision to bank was unclear. Conclusions. A more consistent approach to fertility counseling is essential for adolescent cancer patients. Though first line therapy may be low-risk in terms of long-term impact on fertility, our results demonstrate that transient gonadal dysfunction is common and ongoing chemotherapy may affect spermatogenesis. Should a patient undergo BMT during this period, sperm banking is unlikely to be successful; initial fertility risk assessment should account for this possibility. Pediatr Blood Cancer 2013; 60: 129-132. (C) 2012 Wiley Periodicals, Inc. C1 [Nahata, Leena; Cohen, Laurie E.] Childrens Hosp Boston, Div Endocrinol, Dept Med, Boston, MA 02115 USA. [Lehmann, Leslie E.] Childrens Hosp Boston, Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. [Yu, Richard N.] Childrens Hosp Boston, Dept Urol, Boston, MA 02115 USA. RP Nahata, L (reprint author), Childrens Hosp Boston, Div Endocrinol, Dept Med, 300 Longwood Ave, Boston, MA 02115 USA. EM leena.nahata@childrens.harvard.edu RI Nahata, Leena/E-3727-2011 NR 31 TC 6 Z9 6 U1 0 U2 4 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JAN PY 2013 VL 60 IS 1 BP 129 EP 132 DI 10.1002/pbc.24172 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 038IG UT WOS:000311167800023 PM 22556027 ER PT J AU Goldman, S O'Brien, LM Filipek, PA Rapin, I Herbert, MR AF Goldman, Sylvie O'Brien, Liam M. Filipek, Pauline A. Rapin, Isabelle Herbert, Martha R. TI Motor stereotypies and volumetric brain alterations in children with Autistic Disorder SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Structural imaging; Volumetric brain analysis; Videotape scoring; Motor stereotypies; Autistic Disorder ID DEVELOPMENTAL LANGUAGE DISORDER; REPETITIVE BEHAVIOR; SPECTRUM DISORDER; BASAL GANGLIA; MORPHOMETRIC-ANALYSIS; CEREBRAL-CORTEX; MRI; LOCALIZATION; INDIVIDUALS; REDUCTIONS AB Motor stereotypies are defined as patterned, repetitive, purposeless movements. These stigmatizing motor behaviors represent one manifestation of the third core criterion for an Autistic Disorder (AD) diagnosis, and are becoming viewed as potential early markers of autism. Moreover, motor stereotypies might be a tangible expression of the underlying neurobiology of this neurodevelopmental disorder. In this study, we videoscored stereotypies recorded during semi-structured play sessions from school age children with AD. We examined the effect of severity and persistence over time of stereotypies on brain volumetric changes. Our findings confirmed that the brain volume of school age children with AD is, on average, larger than that of age-matched typically developing children. However, we have failed to detect any sign of volumetric differences in brain regions thought to be particularly linked to the pathophysiology of stereotypies. This negative finding may suggest that, at least with respect to motor stereotypies, functional rather than structural alterations might be the underpinning of these disruptive motor manifestations of autism. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Goldman, Sylvie] Albert Einstein Coll Med, Kennedy Ctr, Saul R Korey Dept Neurol, Bronx, NY 10461 USA. [Goldman, Sylvie; Rapin, Isabelle] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10461 USA. [Goldman, Sylvie; Rapin, Isabelle] Albert Einstein Coll Med, Rose F Kennedy Intellectual & Dev Disabil Res Ctr, Bronx, NY 10461 USA. [O'Brien, Liam M.] Colby Coll, Dept Math & Stat, Waterville, ME 04901 USA. [O'Brien, Liam M.] Univ New England, Coll Grad Programs Publ Hlth, Portland, ME USA. [Filipek, Pauline A.] Univ Texas Hlth Sci Ctr, Dept Pediat, Childrens Learning Inst, Houston, TX 77030 USA. [Filipek, Pauline A.] Univ Texas Hlth Sci Ctr, Div Child & Adolescent Neurol, Houston, TX 77030 USA. [Herbert, Martha R.] Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Herbert, Martha R.] Massachusetts Gen Hosp, TRANSCEND Res Program, Charlestown, MA 02129 USA. RP Goldman, S (reprint author), Albert Einstein Coll Med, Kennedy Ctr, Saul R Korey Dept Neurol, Room 807,1300 Morris Pk Ave, Bronx, NY 10461 USA. EM sylviegold@aol.com FU NICHD NIH HHS [P30 HD071593]; NIDA NIH HHS [P01 DA009467]; NINDS NIH HHS [R01 NS034189, R01 NS048455] NR 47 TC 4 Z9 5 U1 3 U2 22 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1750-9467 J9 RES AUTISM SPECT DIS JI Res. Autism Spectr. Disord. PD JAN-MAR PY 2013 VL 7 IS 1 BP 82 EP 92 DI 10.1016/j.rasd.2012.07.005 PG 11 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 044WN UT WOS:000311656000011 PM 23637709 ER PT J AU Rosenthal, D Hodler, J AF Rosenthal, Daniel Hodler, Juerg TI Untitled SO SKELETAL RADIOLOGY LA English DT Editorial Material C1 [Rosenthal, Daniel] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Hodler, Juerg] Univ Zurich Hosp, CH-8091 Zurich, Switzerland. RP Rosenthal, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM dirosenthal@partners.org; juerg.hodler@usz.ch NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD JAN PY 2013 VL 42 IS 1 BP 1 EP 1 DI 10.1007/s00256-012-1538-7 PG 1 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 043BN UT WOS:000311518000001 ER PT J AU Huang, AJ Halpern, EF Rosenthal, DI AF Huang, Ambrose J. Halpern, Elkan F. Rosenthal, Daniel I. TI Incidence of delayed complications following percutaneous CT-guided biopsy of bone and soft tissue lesions of the spine and extremities: A 2-year prospective study and analysis of risk factors SO SKELETAL RADIOLOGY LA English DT Article DE Biopsy; Complications; Risk factors; Spine; Extremities ID CORE-NEEDLE-BIOPSY; MUSCULOSKELETAL TUMORS; PROSPECTIVE MULTICENTER; DIAGNOSIS; INTERVENTION; ACCURACY; THERAPY; SARCOMA; REPAIR; ERCP AB To prospectively evaluate the incidence of delayed complications (bleeding, pain, infection) following CT-guided biopsies of bone or soft tissue lesions and to identify risk factors that predispose to their occurrence. All adults presenting for CT-guided biopsy of a bone or soft tissue lesion were eligible for the study. Risk factors considered included patient gender and age, bone versus soft tissue, lesion location, lesion depth, anticoagulation, conscious sedation, coaxial biopsy technique, bleeding during the biopsy, dressing type and duration of placement, final diagnosis, needle gauge, number of passes, and number of days to follow-up. Outcomes measured included fever, pain, bruising/hematoma formation, and swelling and were collected by a follow-up phone call within 14 days of the biopsy. Fisher's exact test, the Wald Chi-square test, and univariate, multivariate, and stepwise logistic regression were performed to evaluate the influence of the risk factors on the outcomes. A total of 386 patients participated in the study. The rates of post-biopsy fever, pain, bruising, and swelling were 1.0, 16.1, 15.6, and 9.6 %, respectively. Anticoagulants were identified as a risk factor for fever. Increasing patient age was identified as a risk factor for pain. Female gender and lesion location were identified as risk factors for bruising. Increasing patient age and lesion location were identified as risk factors for swelling. Patient age, female gender, and lesion location are risk factors for delayed minor complications following CT-guided biopsy of a bone or soft tissue lesion. There were no major complications. None of the complications in this series altered patient management. C1 [Huang, Ambrose J.; Halpern, Elkan F.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Huang, AJ (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA. EM ajhuang@partners.org NR 23 TC 7 Z9 8 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD JAN PY 2013 VL 42 IS 1 BP 61 EP 68 DI 10.1007/s00256-012-1433-2 PG 8 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 043BN UT WOS:000311518000009 PM 22729377 ER PT J AU Stengel, A Rivier, J Tache, Y AF Stengel, Andreas Rivier, Jean Tache, Yvette TI Central Actions of Somatostatin-28 and Oligosomatostatin Agonists to Prevent Components of the Endocrine, Autonomic and Visceral Responses to Stress Through Interaction with Different Somatostatin Receptor Subtypes SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE Autonomic nervous system; fecal pellet output; food intake; gastrointestinal motility; octreotide; ODT8-SST; thermogenesis ID CENTRAL-NERVOUS-SYSTEM; CORTICOTROPIN-RELEASING-FACTOR; GASTRIC-ACID-SECRETION; GROWTH-HORMONE SECRETION; COLONIC MOTOR FUNCTION; FOOD-INTAKE; MESSENGER-RNA; C-FOS; RAT HYPOTHALAMUS; INTRACEREBROVENTRICULAR INJECTION AB Somatostatin was discovered four decades ago and since then its physiological role has been extensively investigated, first in relation with its inhibitory effect on growth hormone secretion but soon it expanded to extrapituitary actions influencing various stress-responsive systems. Somatostatin is expressed in distinct brain nuclei and binds to five somatostatin receptor subtypes which are also widely expressed in the brain with a distinct distribution pattern. The last few years witnessed the discovery of highly selective peptide somatostatin receptor agonists and antagonists representing valuable tools to delineate the respective pathways of somatostatin signaling. Here we review the centrally mediated actions of somatostatin and related selective somatostatin receptor subtype agonists to influence the endocrine, autonomic, and visceral components of the stress response and basal behavior as well as thermogenesis. C1 [Stengel, Andreas; Tache, Yvette] Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA. [Stengel, Andreas; Tache, Yvette] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurovisceral Sci & Womens Hlth, Div Digest Dis, Los Angeles, CA 90095 USA. [Stengel, Andreas] Charite Med Ctr, Dept Med, Div Psychosomat Med, Berlin, Germany. [Stengel, Andreas] Charite Med Ctr, Dept Med, Obes Ctr Berlin, Berlin, Germany. [Stengel, Andreas] Univ Berlin, Berlin, Germany. [Rivier, Jean] Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, La Jolla, CA 92037 USA. RP Tache, Y (reprint author), VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU Charite university; VA Research Career Scientist Award; VA Merit Award; NIH [DK 33061, DK 57238] FX A.S. received Charite university funding and an equipment grant of the Sonnenfeld foundation. Y.T. is in receipt of thee VA Research Career Scientist Award, VA Merit Award and NIH R01grants DK 33061 and DK 57238. JR is the Frederik Paulsen Chair in Neurosciences Professor. NR 101 TC 4 Z9 4 U1 0 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD JAN PY 2013 VL 19 IS 1 BP 98 EP 105 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 037HB UT WOS:000311091700014 PM 22950508 ER PT J AU Fleisher, AS Chen, KW Liu, XF Ayutyanont, N Roontiva, A Thiyyagura, P Protas, H Joshi, AD Sabbagh, M Sadowsky, CH Sperling, RA Clark, CM Mintun, MA Pontecorvo, MJ Coleman, RE Doraiswamy, PM Johnson, KA Carpenter, AP Skovronsky, DM Reiman, EM AF Fleisher, Adam S. Chen, Kewei Liu, Xiaofen Ayutyanont, Napatkamon Roontiva, Auttawut Thiyyagura, Pradeep Protas, Hillary Joshi, Abhinay D. Sabbagh, Marwan Sadowsky, Carl H. Sperling, Reisa A. Clark, Christopher M. Mintun, Mark A. Pontecorvo, Michael J. Coleman, R. Edward Doraiswamy, P. M. Johnson, Keith A. Carpenter, Alan P. Skovronsky, Daniel M. Reiman, Eric M. TI Apolipoprotein E epsilon 4 and age effects on florbetapir positron emission tomography in healthy aging and Alzheimer disease SO NEUROBIOLOGY OF AGING LA English DT Article DE Florbetapir; PET; Amyloid PET; Apolipoprotein; Alzheimer; Alzheimer risk; Aging ID MILD COGNITIVE IMPAIRMENT; PITTSBURGH COMPOUND-B; AMYLOID DEPOSITION; NATIONAL INSTITUTE; ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; A-BETA; TYPE-4 ALLELE; OLDER-ADULTS; IN-VIVO AB Objectives: Investigate apolipoprotein E epsilon 4 (APOE4) gene and aging effects on florbetapir F18 positron emission tomography (PET) in normal aging and Alzheimer's disease (AD). Methods: Florbetapir F18 PET images were analyzed from 245 participants, 18-92 years of age, from Avid Radiopharmaceutical's multicenter registered trials, including 86 younger healthy control volunteers (yHC), 61 older healthy control volunteers (oHC), 53 mild cognitive impairment (MCI) patients, and 45 AD dementia patients (DAT). Mean florbetapir standard uptake value ratios (SUVRs) were used to evaluate the effects of APOE4 carrier status, older age, and their interaction in each of these groups. Results: In comparison with non-carriers, the APOE4 carriers in each of the oHC, MCI, and DAT groups had higher mean cortical-to-cerebellar florbetapir SUVRs, patterns of florbetapir PET elevations characteristic of DAT, and a higher proportion meeting florbetapir PET positivity criteria. Only the oHC group had a significant association between mean cortical florbetapir SUVRs and age. In cognitively normal adults, without regards to APOE4 genotype, amyloid began to increase at age 58 (95% confidence interval [CI]: 52.3-63.7), with a predicted typical age of florbetapir positivity occurring around age 71 years. Presence of the APOE4 gene reduced the age of predicted florbetapir positivity in normal aging to around age 56 years, approximately 20 years younger than non-carriers. Interpretation: Cerebral amyloid deposition is associated with APOE4 carrier status in older healthy control subjects and symptomatic AD patients, and increases with age in older cognitively normal individuals. Amyloid imaging positivity appears to begin near age 56 years in cognitively intact APOE4 carriers and age 76 years in APOE4 non-carriers. (C) 2013 Elsevier Inc. All rights reserved. C1 [Fleisher, Adam S.; Chen, Kewei; Liu, Xiaofen; Ayutyanont, Napatkamon; Roontiva, Auttawut; Thiyyagura, Pradeep; Protas, Hillary; Reiman, Eric M.] Banner Alzheimers Inst, Phoenix, AZ USA. [Fleisher, Adam S.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Chen, Kewei] Arizona State Univ, Dept Math, Tempe, AZ 85287 USA. [Joshi, Abhinay D.; Clark, Christopher M.; Mintun, Mark A.; Pontecorvo, Michael J.; Carpenter, Alan P.; Skovronsky, Daniel M.] Avid Radiopharmaceut, Philadelphia, PA USA. [Sadowsky, Carl H.] Nova SE Univ, Ft Lauderdale, FL 33314 USA. [Sperling, Reisa A.; Johnson, Keith A.] Harvard Univ, Brigham & Womens Hosp, Dept Neurol, Sch Med, Boston, MA 02115 USA. [Clark, Christopher M.; Skovronsky, Daniel M.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Mintun, Mark A.] Washington Univ, Sch Med, St Louis, MO USA. [Coleman, R. Edward; Doraiswamy, P. M.] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. [Johnson, Keith A.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Johnson, Keith A.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Reiman, Eric M.] Arizona State Univ W, Dept Psychiat, Coll Med, Phoenix, AZ 85069 USA. [Sabbagh, Marwan; Reiman, Eric M.] Banner Sun Hlth Res Inst, Phoenix, AZ USA. RP Fleisher, AS (reprint author), Banner Alzheimers Inst, Phoenix, AZ USA. EM Adam.fleisher@bannerhealth.com RI Chen, kewei/P-6304-2015 OI Chen, kewei/0000-0001-8497-3069 FU AVID; Eli Lilly; Avid/Lilly; Duke University; Pfizer; Eisai; Lilly; BMS; Baxter; Bayer; GE; Genentech; Amerisciences; Wiley FX Fleisher: has received research support for nonrelated research projects from AVID and Eli Lilly, and has been a paid consultant for Lilly Pharmaceuticals.; Doraiswamy: Has served as a paid advisor/speaker and/or received research grants from Avid/Lilly and several pharmaceutical companies. He owns stock in Sonexa and Clarimedix.; Coleman: Has received research grants (through Duke University) and advisory or speaker fees from Avid/Lilly as well as several other companies in this field.; Sabbagh: Dr Sabbagh receives grant/contract support from Pfizer, Eisai, Lilly, BMS, Baxter, Bayer, GE, Genentech, and Avid. Dr Sabbagh consults for Takeda, BMS, Bayer, Janssen, Lilly, Eisai, Avid, and Amerisciences. Dr Sabbagh receives royalties from Amerisciences and Wiley. NR 55 TC 51 Z9 51 U1 0 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JAN PY 2013 VL 34 IS 1 BP 1 EP 12 DI 10.1016/j.neurobiolaging.2012.04.017 PG 12 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 036LF UT WOS:000311026700001 PM 22633529 ER PT J AU Sylvia, LG Peters, AT Deckersbach, T Nierenberg, AA AF Sylvia, Louisa G. Peters, Amy T. Deckersbach, Thilo Nierenberg, Andrew A. TI Nutrient-Based Therapies for Bipolar Disorder: A Systematic Review SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Review DE Bipolar disorder; Nutrient-based therapy; Alternative treatments ID PLACEBO-CONTROLLED TRIAL; MAGNETIC-RESONANCE-SPECTROSCOPY; ESSENTIAL FATTY-ACIDS; RANDOMIZED CONTROLLED-TRIAL; RED-CELL FOLATE; DOUBLE-BLIND; TRYPTOPHAN DEPLETION; OPEN-LABEL; NERVOUS-SYSTEM; FOLIC-ACID AB Background: Pharmacotherapy is the first line of treatment for bipolar disorder, but many patients continue to experience persistent subthreshold symptoms. Alternative adjunct treatments, including nutritional therapies, may have the potential to alleviate residual symptoms and improve the outcomes of standard pharmacotherapy. The aim of this paper is to critically review the current clinical evidence and mechanisms of action of nutrient-based therapies alone or in combination with commonly used pharmacotherapies for mania and bipolar depression. Methods: We conducted a Medline search for clinical trials conducted with humans, published in English from 1960 to 2012 using nutritional supplements such as n-3, chromium, inositol, choline, magnesium, folate and tryptophan alone or in combination with pharmacotherapies for the treatment of bipolar disorder. Results: Preliminary data yields conflicting but mainly positive evidence for the use of n-3 fatty acids and chromium in the treatment of bipolar depression. Limited evidence found that inositol may be helpful for bipolar depression, but larger sample sizes are needed. Preliminary randomized, controlled trials suggest that choline, magnesium, folate and tryptophan may be beneficial for reducing symptoms of mania. Conclusions: Given the potential public health impact of identifying adjunct treatments that improve psychiatric as well as physical health outcomes, nutritional treatments appear promising for the management of bipolar disorder but require further study. Copyright (C) 2012 S. Karger AG, Basel C1 [Sylvia, Louisa G.; Peters, Amy T.; Deckersbach, Thilo; Nierenberg, Andrew A.] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA. [Sylvia, Louisa G.; Peters, Amy T.; Deckersbach, Thilo; Nierenberg, Andrew A.] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA. [Sylvia, Louisa G.; Deckersbach, Thilo; Nierenberg, Andrew A.] Harvard Univ, Sch Med, Boston, MA USA. RP Sylvia, LG (reprint author), Massachusetts Gen Hosp, Bipolar Clin, 50 Staniford St,Suite 580, Boston, MA 02114 USA. EM lsylvia2@partners.org NR 124 TC 13 Z9 14 U1 7 U2 38 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PY 2013 VL 82 IS 1 BP 10 EP 19 DI 10.1159/000341309 PG 10 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 033KX UT WOS:000310796100002 PM 23147067 ER PT J AU Kim, YJ Lee, HJ Kim, TM Eisinger-Mathason, TSK Zhang, AY Schmidt, B Karl, DL Nakazawa, MS Park, PJ Simon, MC Yoon, SS AF Kim, Yeo-Jung Lee, Hae-June Kim, Tae-Min Eisinger-Mathason, T. S. Karin Zhang, Alexia Y. Schmidt, Benjamin Karl, Daniel L. Nakazawa, Michael S. Park, Peter J. Simon, M. Celeste Yoon, Sam S. TI Overcoming evasive resistance from vascular endothelial growth factor a inhibition in sarcomas by genetic or pharmacologic targeting of hypoxia-inducible factor 1 alpha SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE sarcomas; hypoxia; HIF-1 alpha; VEGF-A ID SOFT-TISSUE SARCOMA; ELECTRON-BEAM RADIOTHERAPY; ANTI-ANGIOGENIC THERAPY; TUMOR ANGIOGENESIS; MOUSE MODEL; RANDOMIZED-TRIAL; CANCER-THERAPY; UP-REGULATION; METASTASIS; ACTIVATION AB Increased levels of hypoxia and hypoxia-inducible factor 1 alpha (HIF-1 alpha) in human sarcomas correlate with tumor progression and radiation resistance. Prolonged antiangiogenic therapy of tumors not only delays tumor growth but may also increase hypoxia and HIF-1 alpha activity. In our recent clinical trial, treatment with the vascular endothelial growth factor A (VEGF-A) antibody, bevacizumab, followed by a combination of bevacizumab and radiation led to near complete necrosis in nearly half of sarcomas. Gene Set Enrichment Analysis of microarrays from pretreatment biopsies found that the Gene Ontology category "Response to hypoxia" was upregulated in poor responders and that the hierarchical clustering based on 140 hypoxia-responsive genes reliably separated poor responders from good responders. The most commonly used chemotherapeutic drug for sarcomas, doxorubicin (Dox), was recently found to block HIF-1 alpha binding to DNA at low metronomic doses. In four sarcoma cell lines, HIF-1 alpha shRNA or Dox at low concentrations blocked HIF-1 alpha induction of VEGF-A by 84-97% and carbonic anhydrase 9 by 83-93%. HT1080 sarcoma xenografts had increased hypoxia and/or HIF-1 alpha activity with increasing tumor size and with anti-VEGF receptor antibody (DC101) treatment. Combining DC101 with HIF-1 alpha shRNA or metronomic Dox had a synergistic effect in suppressing growth of HT1080 xenografts, at least in part via induction of tumor endothelial cell apoptosis. In conclusion, sarcomas respond to increased hypoxia by expressing HIF-1 alpha target genes that may promote resistance to antiangiogenic and other therapies. HIF-1 alpha inhibition blocks this evasive resistance and augments destruction of the tumor vasculature. C1 [Lee, Hae-June; Zhang, Alexia Y.; Schmidt, Benjamin; Karl, Daniel L.; Yoon, Sam S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Kim, Yeo-Jung; Yoon, Sam S.] Univ Penn, Sch Med, Dept Canc Biol, Philadelphia, PA 19104 USA. [Kim, Yeo-Jung; Eisinger-Mathason, T. S. Karin; Nakazawa, Michael S.; Simon, M. Celeste] Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Lee, Hae-June] Korea Inst Radiol & Med Sci, Div Radiat Effects, Seoul, South Korea. [Kim, Tae-Min; Park, Peter J.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA USA. [Simon, M. Celeste] Univ Penn, Sch Med, Howard Hughes Med Inst, Philadelphia, PA 19104 USA. RP Yoon, SS (reprint author), Massachusetts Gen Hosp, Dept Surg, Yawkey 7,55 Fruit St, Boston, MA 02114 USA. EM syoon@partners.org FU NIH [1R21 CA117128-02, 1R01 CA158301-01]; Society for Surgical Oncology Clinical Investigator Award FX Grant sponsor: NIH; Grant numbers: 1R21 CA117128-02, 1R01 CA158301-01; Grant sponsor: Society for Surgical Oncology Clinical Investigator Award NR 48 TC 17 Z9 17 U1 0 U2 23 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 1 PY 2013 VL 132 IS 1 BP 29 EP 41 DI 10.1002/ijc.27666 PG 13 WC Oncology SC Oncology GA 029HZ UT WOS:000310486800004 PM 22684860 ER PT J AU Bourisly, AK Haynes, C Bourisly, N Mody, M AF Bourisly, Ali K. Haynes, Charles Bourisly, Nibal Mody, Maria TI Neural correlates of diacritics in Arabic: An fMRI study SO JOURNAL OF NEUROLINGUISTICS LA English DT Article DE fMRI; Diacritics; Arabic; Word recognition ID VISUAL WORD RECOGNITION; ANTERIOR CINGULATE CORTEX; LEXICAL ACCESS; MENTAL LEXICON; HEBREW; VOWELS; ORTHOGRAPHY; ACTIVATION; STRATEGIES; MORPHOLOGY AB Though diacritics are a central feature of Arabic reading, their cognitive and neural effects remain less well understood. The present study used functional magnetic resonance imaging (fMRI) to investigate differences between brain activation patterns associated with real words with versus without diacritics in adult Arabic readers using a lexical decision task. We found no significant difference in accuracy between real words with and without diacritics. However, real words with no diacritics yielded shorter response times and stronger activation in the hippocampus and middle temporal gyrus, possibly reflecting a search among multiple lexical entries that may be associated with these words. In contrast, real words with diacritics yielded longer response times and activated the insula and inferior frontal areas, suggesting an engagement of phonological and semantic processes in recognizing words with diacritics. Taken together, the results support a linguistic role for diacritics in isolated word recognition even in experienced Arabic readers. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Bourisly, Ali K.] Worcester Polytech Inst, Dept Biomed Engn, Worcester, MA 01609 USA. [Bourisly, Ali K.] Univ Massachusetts, Adv MRI Ctr, Dept Radiol, Sch Med, Amherst, MA 01003 USA. [Bourisly, Ali K.] Kuwait Univ, Dept Physiol, Fac Med, Kuwait, Kuwait. [Haynes, Charles] MGH Inst Hlth Profess, Dept Commun Sci & Disorders, Charlestown, MA 02129 USA. [Bourisly, Nibal] Kuwait Univ, Dept Mass Commun, Coll Arts, Shuwaykh, Kuwait. [Mody, Maria] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Mody, Maria] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Bourisly, AK (reprint author), Worcester Polytech Inst, Dept Biomed Engn, 100 Inst Rd, Worcester, MA 01609 USA. EM ali.b@hsc.edu.kw FU Kuwait Foundation for the Advancement of Sciences (KFAS) [2008-6102-01] FX We would like to thank all the participants in the study, and two anonymous reviewers for their comments. This work was partly supported by Grant 2008-6102-01 from the Kuwait Foundation for the Advancement of Sciences (KFAS), awarded to Ali Bourisly. NR 41 TC 3 Z9 3 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0911-6044 J9 J NEUROLINGUIST JI J. Neurolinguist. PD JAN PY 2013 VL 26 IS 1 BP 195 EP 206 DI 10.1016/j.jneuroling.2012.07.004 PG 12 WC Linguistics; Neurosciences; Psychology, Experimental SC Linguistics; Neurosciences & Neurology; Psychology GA 028HM UT WOS:000310413400012 ER PT J AU Kapinas, K Grandy, R Ghule, P Medina, R Becker, K Pardee, A Zaidi, SK Lian, J Stein, J van Wijnen, A Stein, G AF Kapinas, Kristina Grandy, Rodrigo Ghule, Prachi Medina, Ricardo Becker, Klaus Pardee, Arthur Zaidi, Sayyed K. Lian, Jane Stein, Janet van Wijnen, Andre Stein, Gary TI The abbreviated pluripotent cell cycle SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Review ID EMBRYONIC STEM-CELLS; HISTONE GENE-TRANSCRIPTION; HUMAN SOMATIC-CELLS; FACTOR HINF-D; PROTEIN-DNA INTERACTIONS; HEMATOPOIETIC PROGENITOR CELLS; HUMAN H4-HISTONE GENE; S-PHASE ENTRY; SELF-RENEWAL; H4 GENE AB Human embryonic stem cells (hESCs) and induced pluripotent stem cells proliferate rapidly and divide symmetrically producing equivalent progeny cells. In contrast, lineage committed cells acquire an extended symmetrical cell cycle. Self-renewal of tissue-specific stem cells is sustained by asymmetric cell division where one progeny cell remains a progenitor while the partner progeny cell exits the cell cycle and differentiates. There are three principal contexts for considering the operation and regulation of the pluripotent cell cycle: temporal, regulatory, and structural. The primary temporal context that the pluripotent self-renewal cell cycle of hESCs is a short G1 period without reducing periods of time allocated to S phase, G2, and mitosis. The rules that govern proliferation in hESCs remain to be comprehensively established. However, several lines of evidence suggest a key role for the naive transcriptome of hESCs, which is competent to stringently regulate the embryonic stem cell (ESC) cell cycle. This supports the requirements of pluripotent cells to self-propagate while suppressing expression of genes that confer lineage commitment and/or tissue specificity. However, for the first time, we consider unique dimensions to the architectural organization and assembly of regulatory machinery for gene expression in nuclear microenviornments that define parameters of pluripotency. From both fundamental biological and clinical perspectives, understanding control of the abbreviated ESC cycle can provide options to coordinate control of proliferation versus differentiation. Wound healing, tissue engineering, and cell-based therapy to mitigate developmental aberrations illustrate applications that benefit from knowledge of the biology of the pluripotent cell cycle. J. Cell. Physiol. 228: 920, 2013. (c) 2012 Wiley Periodicals, Inc. C1 [Kapinas, Kristina; Grandy, Rodrigo; Ghule, Prachi; Medina, Ricardo; Becker, Klaus; Zaidi, Sayyed K.; Lian, Jane; Stein, Janet; van Wijnen, Andre; Stein, Gary] Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01605 USA. [Pardee, Arthur] Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Stein, G (reprint author), Univ Massachusetts, Sch Med, Dept Cell Biol, 55 Lake Ave N,S3-310, Worcester, MA 01605 USA. EM gary.stein@umassmed.edu OI Zaidi, Kaleem/0000-0001-6664-5168 FU NIH [AR039588, AR48818, AG035886, CA82834139322]; National Institutes of Health [AR039588, AR48818, AG035886, CA82834, CA139322] FX Contract grant sponsor: NIH;; Contract grant numbers: AR039588, AR48818, AG035886, CA82834139322.; We thank Patricia Jamieson and Priscilla Vazquez for editorial assistance in the preparation of the manuscript. Studies described in this review were supported by grants from the National Institutes of Health (AR039588, AR48818, AG035886, CA82834, and CA139322). NR 163 TC 37 Z9 37 U1 2 U2 34 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JAN PY 2013 VL 228 IS 1 BP 9 EP 20 DI 10.1002/jcp.24104 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 018QW UT WOS:000309678000002 PM 22552993 ER PT J AU Manabe, Y Miyatake, S Takagi, M Nakamura, M Okeda, A Nakano, T Hirshman, MF Goodyear, LJ Fujii, NL AF Manabe, Yasuko Miyatake, Shouta Takagi, Mayumi Nakamura, Mio Okeda, Ai Nakano, Taemi Hirshman, Michael F. Goodyear, Laurie J. Fujii, Nobuharu L. TI Characterization of an Acute Muscle Contraction Model Using Cultured C2C12 Myotubes SO PLOS ONE LA English DT Article ID ACTIVATED PROTEIN-KINASE; SKELETAL-MUSCLE; GLUCOSE-TRANSPORT; EXERCISE; STIMULATION; EXPRESSION; INSULIN; AKT AB A cultured C2C12 myotube contraction system was examined for application as a model for acute contraction-induced phenotypes of skeletal muscle. C2C12 myotubes seeded into 4-well rectangular plates were placed in a contraction system equipped with a carbon electrode at each end. The myotubes were stimulated with electric pulses of 50 V at 1 Hz for 3 ms at 997-ms intervals. Approximately 80% of the myotubes were observed to contract microscopically, and the contractions lasted for at least 3 h with electrical stimulation. Calcium ion (Ca2+) transient evoked by the electric pulses was detected fluorescently with Fluo-8. Phosphorylation of protein kinase B/Akt (Akt), 5' AMP-activated protein kinase (AMPK), p38 mitogen-activated protein kinase (p38), and c-Jun NH2-terminal kinase (JNK)1/2, which are intracellular signaling proteins typically activated in exercised/contracted skeletal muscle, was observed in the electrically stimulated C2C12 myotubes. The contractions induced by the electric pulses increased glucose uptake and depleted glycogen in the C2C12 myotubes. C2C12 myotubes that differentiated after exogenous gene transfection by a lipofection or an electroporation method retained their normal contractile ability by electrical stimulation. These findings show that our C2C12 cell contraction system reproduces the muscle phenotypes that arise in vivo (exercise), in situ (hindlimb muscles in an anesthetized animal), and in vitro (dissected muscle tissues in incubation buffer) by acute muscle contraction, demonstrating that the system is applicable for the analysis of intracellular events evoked by acute muscle contraction. C1 [Manabe, Yasuko; Miyatake, Shouta; Takagi, Mayumi; Nakamura, Mio; Okeda, Ai; Nakano, Taemi; Fujii, Nobuharu L.] Tokyo Metropolitan Univ, Grad Sch Human Hlth Sci, Dept Hlth Promot Sci, Tokyo 158, Japan. [Hirshman, Michael F.; Goodyear, Laurie J.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. [Hirshman, Michael F.; Goodyear, Laurie J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Fujii, NL (reprint author), Tokyo Metropolitan Univ, Grad Sch Human Hlth Sci, Dept Hlth Promot Sci, Tokyo 158, Japan. EM fujiin@tmu.ac.jp RI Fujii, Nobuharu/J-2724-2014 OI Fujii, Nobuharu/0000-0002-0974-3033 FU Japan Society for the Promotion of Science Kakenhi [21240063]; Funding Program for World-Leading Innovative R&D on Science and Technology by the Council for Science and Technology Policy [LS102]; National Institutes of Health [AR45670, AR42238]; [21700657] FX This work was supported by a Grant-in-Aid for Young Scientists B 21700657 (to Y.M.), the Japan Society for the Promotion of Science Kakenhi 21240063 (to N.L.F.), Funding Program for World-Leading Innovative R&D on Science and Technology by the Council for Science and Technology Policy LS102 (to N.L.F.), and National Institutes of Health Grants AR45670 and AR42238 (to L.J.G.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 21 TC 26 Z9 27 U1 2 U2 39 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 31 PY 2012 VL 7 IS 12 AR e52592 DI 10.1371/journal.pone.0052592 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 075GO UT WOS:000313872600019 PM 23300713 ER PT J AU Zhu, J Siclari, VA Liu, F Spatz, JM Chandra, A Pajevic, PD Qin, L AF Zhu, Ji Siclari, Valerie A. Liu, Fei Spatz, Jordan M. Chandra, Abhishek Pajevic, Paola Divieti Qin, Ling TI Amphiregulin-EGFR Signaling Mediates the Migration of Bone Marrow Mesenchymal Progenitors toward PTH-Stimulated Osteoblasts and Osteocytes SO PLOS ONE LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; INTERMITTENT PARATHYROID-HORMONE; FACTOR RECEPTOR; STEM-CELLS; IN-VIVO; OSTEOPROGENITOR CELLS; PTH/PTHRP RECEPTOR; ANABOLIC ACTIONS; EXPRESSION; DIFFERENTIATION AB Intermittent administration of parathyroid hormone (PTH) dramatically increases bone mass and currently is one of the most effective treatments for osteoporosis. However, the detailed mechanisms are still largely unknown. Here we demonstrate that conditioned media from PTH-treated osteoblastic and osteocytic cells contain soluble chemotactic factors for bone marrow mesenchymal progenitors, which express a low amount of PTH receptor (PTH1R) and do not respond to PTH stimulation by increasing cAMP production or migrating toward PTH alone. Conditioned media from PTH-treated osteoblasts elevated phosphorylated Akt and p38MAPK amounts in mesenchymal progenitors and inhibition of these pathways blocked the migration of these progenitors toward conditioned media. Our previous and current studies revealed that PTH stimulates the expression of amphiregulin, an epidermal growth factor (EGF)-like ligand that signals through the EGF receptor (EGFR), in both osteoblasts and osteocytes. Interestingly, conditioned media from PTH-treated osteoblasts increased EGFR phosphorylation in mesenchymal progenitors. Using several different approaches, including inhibitor, neutralizing antibody, and siRNA, we demonstrate that PTH increases the release of amphiregulin from osteoblastic cells, which acts on the EGFRs expressed on mesenchymal progenitors to stimulate the Akt and p38MAPK pathways and subsequently promote their migration in vitro. Furthermore, inactivation of EGFR signaling specifically in osteoprogenitors/osteoblasts attenuated the anabolic actions of PTH on bone formation. Taken together, these results suggest a novel mechanism for the therapeutic effect of PTH on osteoporosis and an important role of EGFR signaling in mediating PTH's anabolic actions on bone. C1 [Zhu, Ji; Siclari, Valerie A.; Liu, Fei; Chandra, Abhishek; Qin, Ling] Univ Penn, Perelman Sch Med, Dept Orthopaed Surg, McKay Orthopaed Res Lab, Philadelphia, PA 19104 USA. [Liu, Fei] Shanghai Ninth Peoples Hosp, Dept Plast & Reconstruct Surg, Shanghai, Peoples R China. [Spatz, Jordan M.; Pajevic, Paola Divieti] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Spatz, Jordan M.; Pajevic, Paola Divieti] Harvard Univ, Sch Med, Boston, MA USA. RP Qin, L (reprint author), Univ Penn, Perelman Sch Med, Dept Orthopaed Surg, McKay Orthopaed Res Lab, Philadelphia, PA 19104 USA. EM qinling@mail.med.upenn.edu OI Chandra, Abhishek/0000-0001-9423-9669 FU National Institutes of Health [K01-DK071988, UH2-AR059655]; New Jersey Stem Cell Research Grant; National Osteoporosis Foundation; National Cancer Institute [R25 CA101871-07] FX This publication was made possible by support from the National Institutes of Health K01 grants K01-DK071988 (to LQ), UH2-AR059655 (to PDP), New Jersey Stem Cell Research Grant (to LQ), National Osteoporosis Foundation (to LQ), and grant R25 CA101871-07 from the National Cancer Institute (to VS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 21 Z9 22 U1 2 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 31 PY 2012 VL 7 IS 12 AR e50099 DI 10.1371/journal.pone.0050099 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 075GO UT WOS:000313872600001 PM 23300521 ER PT J AU Yi, ZH Fan, XD Wang, JJ Liu, DT Freudenreich, O Goff, D Henderson, DC AF Yi, Zhenghui Fan, Xiaoduo Wang, JiJun Liu, Dengtang Freudenreich, Oliver Goff, Donald Henderson, David C. TI Rosiglitazone and cognitive function in clozapine-treated patients with schizophrenia: A pilot study SO PSYCHIATRY RESEARCH LA English DT Article DE Rosiglitazone; Schizophrenia; Cognition; Clozapine; Insulin resistance ID ALZHEIMERS-DISEASE; SYNAPTIC PLASTICITY; GLUCOSE-METABOLISM; DIABETES-MELLITUS; GAMMA AGONISTS; DOUBLE-BLIND; INSULIN; IMPAIRMENT; RISPERIDONE; MECHANISMS AB Studies have shown that insulin resistance is associated with cognitive impairment. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists improve insulin sensitivity. The purpose of this study was to evaluate the effect of rosiglitazone, a PPAR-gamma agonist, on cognition in clozapine-treated patients with schizophrenia. In an eight-week double-blind, placebo-controlled pilot trial, clozapine-treated patients with schizophrenia were randomized to receive rosiglitazone (4 mg/day) or placebo. A neuropsychological battery including the Digit Span subtest from the Wechsler Adult Intelligence Scale-III (WAIS-III), the verbal fluency test, the Hopkins Verbal Learning Test (HVLT), the Trail-Making Test (TMT) and the Wisconsin Card Sorting Test (WCST) was administered at baseline and week eight. Nineteen patients completed the study. There were no significant differences on any demographic or general clinical variables between the rosiglitazone group (n=9) and the placebo group (n=10). When baseline scores were controlled, there were no significant differences in change scores of cognitive performance over eight weeks between the two groups. In this pilot study, rosiglitazone had no cognitive benefit in clozapine-treated patients with schizophrenia. Future studies with longer treatment duration and larger sample size are needed to further explore the potential role of rosiglitazone in improving cognitive function in patients with schizophrenia. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Yi, Zhenghui; Wang, JiJun; Liu, Dengtang] Shanghai Jiao Tong Univ, Sch Med, Shanghai Mental Hlth Ctr, Shanghai 200030, Peoples R China. [Fan, Xiaoduo; Freudenreich, Oliver; Goff, Donald; Henderson, David C.] Massachusetts Gen Hosp, Dept Psychiat, Schizophrenia Program, Boston, MA 02114 USA. [Fan, Xiaoduo; Freudenreich, Oliver; Goff, Donald; Henderson, David C.] Harvard Univ, Sch Med, Boston, MA USA. RP Fan, XD (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM xfan@partners.org FU Stanley Foundation; NARSAD Yong Investigator Award; Harvard Clinical and Translational Science Center [M01-RR-01066, 1 UL1 RR025758-03]; National Center for Research Resources; Shanghai Municipal Health Bureau Research Projects of China [2009097] FX This project was funded by the Stanley Foundation and a NARSAD Yong Investigator Award (DCH). The project described was supported by Grant numbers M01-RR-01066 and 1 UL1 RR025758-03, Harvard Clinical and Translational Science Center, from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. This project was also funded by Shanghai Municipal Health Bureau Research Projects of China (2009097) (ZY) NR 32 TC 3 Z9 3 U1 2 U2 12 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD DEC 30 PY 2012 VL 200 IS 2-3 BP 79 EP 82 DI 10.1016/j.psychres.2012.05.020 PG 4 WC Psychiatry SC Psychiatry GA 073TF UT WOS:000313764700003 PM 22727707 ER PT J AU Hall, MH Smoller, JW Cook, NR Schulze, K Lee, PH Taylor, G Bramon, E Coleman, MJ Murray, RM Salisbury, DF Levy, DL AF Hall, Mei-Hua Smoller, Jordan W. Cook, Nancy R. Schulze, Katja Lee, Phil Hyoun Taylor, Grantley Bramon, Elvira Coleman, Michael J. Murray, Robin M. Salisbury, Dean F. Levy, Deborah L. TI Patterns of deficits in brain function in bipolar disorder and schizophrenia: A cluster analytic study SO PSYCHIATRY RESEARCH LA English DT Article DE Bipolar disorder; Schizophrenia; K-means clustering; Neurophysiologic profiles ID DURATION MISMATCH NEGATIVITY; EVENT-RELATED POTENTIALS; NEUROPHYSIOLOGICAL ENDOPHENOTYPES; GAMMA OSCILLATIONS; GENE-EXPRESSION; MENTAL-ILLNESS; P300; PSYCHOSIS; P50; SUPPRESSION AB Historically, bipolar disorder and schizophrenia have been considered distinct disorders with different etiologies. Growing evidence suggests that overlapping genetic influences contribute to risk for these disorders and that each disease is genetically heterogeneous. Using cluster analytic methods, we empirically identified homogeneous subgroups of patients, their relatives, and controls based on distinct neurophysiologic profiles. Seven phenotypes were collected from two independent cohorts at two institutions. K-means clustering was used to identify neurophysiologic profiles. In the analysis of all participants, three distinct profiles emerged: "globally impaired", "sensory processing", and "high cognitive". In a secondary analysis, restricted to patients only, we observed a similar clustering into three profiles. The neurophysiological profiles of the Schizophrenia (SZ) and Bipolar Disorder (BPD) patients did not support the Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic distinction between these two disorders. Smokers in the globally impaired group smoked significantly more cigarettes than those in the sensory processing or high cognitive groups. Our results suggest that empirical analyses of neurophysiological phenotypes can identify potentially biologically relevant homogenous subgroups independent of diagnostic boundaries. We hypothesize that each neurophysiology subgroup may share similar genotypic profiles, which may increase statistical power to detect genetic risk factors. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Hall, Mei-Hua; Coleman, Michael J.; Levy, Deborah L.] Harvard Univ, Sch Med, McLean Hosp, Psychol Res Lab, Belmont, MA 02478 USA. [Hall, Mei-Hua; Taylor, Grantley; Salisbury, Dean F.] Harvard Univ, Sch Med, McLean Hosp, Cognit Neurosci Lab, Belmont, MA 02478 USA. [Hall, Mei-Hua; Smoller, Jordan W.; Lee, Phil Hyoun] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Schulze, Katja; Bramon, Elvira; Murray, Robin M.] Kings Coll London, Inst Psychiat, Div Psychol Med, London WC2R 2LS, England. [Cook, Nancy R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA. RP Hall, MH (reprint author), Harvard Univ, Sch Med, McLean Hosp, Psychol Res Lab, Mailstop 223,115 Mill St, Belmont, MA 02478 USA. EM mhall@mclean.harvard.edu RI Murray, Robin/F-8658-2012 OI Murray, Robin/0000-0003-0829-0519 FU McLean Hospital; NARSAD Sidney R. Baer, Jr. Foundation; Essel Foundation; National Institute of Mental Health [1K01MH086714, 5R01MH071523, MH58704, R01MH079799, K24MH094614] FX This work was supported by the Rappaport Mental Health Research Scholar Award, McLean Hospital to M-HH, NARSAD Sidney R. Baer, Jr. Foundation Awards to M-HH and DLL, Grants from the Essel Foundation to DLL, and from the National Institute of Mental Health [1K01MH086714 to M-HH, 5R01MH071523 to DLL, MH58704 to DFS, and R01MH079799 and K24MH094614 to JWS]. NR 60 TC 8 Z9 9 U1 1 U2 17 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD DEC 30 PY 2012 VL 200 IS 2-3 BP 272 EP 280 DI 10.1016/j.psychres.2012.07.052 PG 9 WC Psychiatry SC Psychiatry GA 073TF UT WOS:000313764700034 PM 22925372 ER PT J AU Pompili, M Gibiino, S Innamorati, M Serafini, G Del Casale, A De Risio, L Palermo, M Montebovi, F Campi, S De Luca, V Sher, L Tatarelli, R Biondi, M Duval, F Serretti, A Girardi, P AF Pompili, Maurizio Gibiino, Sara Innamorati, Marco Serafini, Gianluca Del Casale, Antonio De Risio, Luisa Palermo, Mario Montebovi, Franco Campi, Sandra De Luca, Vincenzo Sher, Leo Tatarelli, Roberto Biondi, Massimo Duval, Fabrice Serretti, Alessandro Girardi, Paolo TI Prolactin and thyroid hormone levels are associated with suicide attempts in psychiatric patients SO PSYCHIATRY RESEARCH LA English DT Article DE Attempted suicide; Biological predictors; Mood disorder; Thyroid hormones; Depression ID MAJOR DEPRESSIVE EPISODE; TOWER-OF-BABEL; REVISED NOMENCLATURE; BEHAVIOR; DISORDERS; METABOLITES; TESTS; MINI; AXIS; TRH AB The aim of this study is to evaluate biological factors associated with recent suicidal attempts in a naturalistic sample. A total of 439 patients suffering from major depression disorder (MDD), bipolar disorder (BD) and psychotic disorders (schizophrenia, schizoaffective disorder and psychosis not otherwise specified), who were consecutively assessed in the Emergency Department of an Italian Hospital (January 2008-December 2009), were included. In the whole sample, suicide attempters and non-attempters differed with regard to free triiodothyronine (FT3) and prolactin values only. A univariate general linear model indicated significant effects of sex (F-1;379=9.29; P=0.002), suicidal status (F-1;379=4.49; P=0.04) and the interaction between sex and suicidal status (F-1;379=5.17; P=0.02) on prolactin levels. A multinomial logistic regression model indicated that suicidal attempters were 2.27 times (odds ratio (OR)=0.44; 95% confidence interval (95%CI): 0.23/0.82; P=0.01) less likely to have higher FT3 values than non-attempters; while prolactin values failed to reach statistical significance (OR=0.99; 95%CI: 0.98/1.00; P=0.051). Both prolactin and thyroid hormones may be involved in a complex compensatory mechanism to correct reduced central serotonin activity. Further studies may help in understanding how these findings can be used by clinicians in assessing suicide risk. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Pompili, Maurizio; Innamorati, Marco; Serafini, Gianluca; Del Casale, Antonio; De Risio, Luisa; Palermo, Mario; Montebovi, Franco; Campi, Sandra; Tatarelli, Roberto; Girardi, Paolo] Univ Roma La Sapienza, Dept Neurosci Mental Hlth & Sensory Organs, Suicide Prevent Ctr, St Andrea Hosp, I-00189 Rome, Italy. [Pompili, Maurizio] Harvard Univ, Sch Med, McLean Hosp, Boston, MA USA. [Gibiino, Sara; Serretti, Alessandro] Univ Bologna, Inst Psychiat, Bologna, Italy. [De Luca, Vincenzo] Univ Toronto, Dept Psychiat, CAMH, Toronto, ON, Canada. [Sher, Leo] Mt Sinai Sch Med, New York, NY USA. [Sher, Leo] James J Peters Vet Adm Med Ctr, New York, NY USA. [Duval, Fabrice] Ctr Hosp, Rouffach, France. [Biondi, Massimo] Univ Roma La Sapienza, Dept Psychiat & Psychol Med, I-00189 Rome, Italy. RP Pompili, M (reprint author), Univ Roma La Sapienza, Dept Neurosci Mental Hlth & Sensory Organs, Suicide Prevent Ctr, St Andrea Hosp, Via Grottarossa 1035-1039, I-00189 Rome, Italy. EM maurizio.pompili@uniroma1.it RI Innamorati, Marco/H-8877-2013; OI Innamorati, Marco/0000-0003-1389-2290; Tatarelli, Roberto/0000-0003-4396-2632; biondi, massimo/0000-0001-8777-5498; Pompili, Maurizio/0000-0003-1886-4977; Del Casale, Antonio/0000-0003-2427-6944 FU Italian Ministry of University Research-PRIN Project FX Supported, in part, by a grant from the Italian Ministry of University Research-PRIN Project (to M.P., G.S., R.T., P.G.) NR 30 TC 11 Z9 13 U1 0 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD DEC 30 PY 2012 VL 200 IS 2-3 BP 389 EP 394 DI 10.1016/j.psychres.2012.05.010 PG 6 WC Psychiatry SC Psychiatry GA 073TF UT WOS:000313764700051 PM 22748186 ER PT J AU Mueller-Pfeiffer, C Rufibach, K Perron, N Wyss, D Kuenzler, C Prezewowsky, C Pitman, RK Rufer, M AF Mueller-Pfeiffer, Christoph Rufibach, Kaspar Perron, Noelle Wyss, Daniela Kuenzler, Cornelia Prezewowsky, Cornelia Pitman, Roger K. Rufer, Michael TI Global functioning and disability in dissociative disorders SO PSYCHIATRY RESEARCH LA English DT Article DE Quality of care; Comorbidity; Outpatients; Psychiatry in Europe ID MULTIPLE PERSONALITY-DISORDER; ASSESSMENT SCHEDULE-II; IDENTITY DISORDER; DEPERSONALIZATION DISORDER; PSYCHIATRIC OUTPATIENTS; AXIS-I; CHILDHOOD ABUSE; WHODAS-II; COMORBIDITY; PREVALENCE AB Dissociative disorders are frequent comorbid conditions of other mental disorders. Yet, there is controversy about their clinical relevance, and little systematic research has been done on how they influence global functioning. Outpatients and day care patients (N=160) of several psychiatric units in Switzerland were assessed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV Axis I Disorders, Structured Clinical Interview for DSM-IV Dissociative Disorders, Global Assessment of Functioning Scale, and World Health Organization Disability Assessment Schedule-II. The association between subjects with a dissociative disorder (N=30) and functional impairment after accounting for non-dissociative axis I disorders was evaluated by linear regression models. We found a proportion of 18.8% dissociative disorders (dissociative amnesia=0%, dissociative fugue=0.6%, depersonalization disorder=4.4%, dissociative identity disorder=7.5%, dissociative disorder-not-otherwise-specified=6.3%) across treatment settings. Adjusted for other axis I disorders, subjects with a comorbid dissociative identity disorder or dissociative disorder-not-otherwise-specified had a median global assessment of functioning score that was 0.86 and 0.88 times, respectively, the score of subjects without a comorbid dissociative disorder. These findings support the hypothesis that complex dissociative disorders, i.e., dissociative identity disorder and dissociative disorder-not-otherwise-specified, contribute to functional impairment above and beyond the impact of co-existing non-dissociative axis I disorders, and that they qualify as "serious mental illness". (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Mueller-Pfeiffer, Christoph; Rufer, Michael] Univ Zurich Hosp, Dept Psychiat & Psychotherapy, CH-8091 Zurich, Switzerland. [Mueller-Pfeiffer, Christoph; Perron, Noelle; Wyss, Daniela; Kuenzler, Cornelia; Prezewowsky, Cornelia] Psychiat Serv Cty St Gallen N, Ctr Educ & Res COEUR, CH-9500 Wil, Switzerland. [Mueller-Pfeiffer, Christoph; Pitman, Roger K.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Mueller-Pfeiffer, Christoph; Pitman, Roger K.] Harvard Univ, Sch Med, Boston, MA USA. [Rufibach, Kaspar] Univ Zurich, Inst Social & Prevent Med, Div Biostat, CH-8001 Zurich, Switzerland. [Perron, Noelle] Univ Bern, CH-3012 Bern, Switzerland. RP Mueller-Pfeiffer, C (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bldg 120,2nd Ave, Charlestown, MA 02129 USA. EM christoph.mueller-pfeiffer@access.uzh.ch RI Rufibach, Kaspar/F-1163-2010; OI Rufer, Michael/0000-0003-4964-4213 FU Center of Education and Research (COEUR), Psychiatric Services of the County of St. Gallen-North, Switzerland; Fritz Rohrer Fonds, Zurich, Switzerland FX The study was funded by the Center of Education and Research (COEUR), Psychiatric Services of the County of St. Gallen-North, Switzerland, and the Fritz Rohrer Fonds, Zurich, Switzerland. NR 46 TC 18 Z9 18 U1 1 U2 27 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD DEC 30 PY 2012 VL 200 IS 2-3 BP 475 EP 481 DI 10.1016/j.psychres.2012.04.028 PG 7 WC Psychiatry SC Psychiatry GA 073TF UT WOS:000313764700064 PM 22578820 ER PT J AU Boden, MT Bernstein, A Walser, RD Bui, L Alvarez, J Bonn-Miller, MO AF Boden, Matthew Tyler Bernstein, Amit Walser, Robyn D. Bui, Leena Alvarez, Jennifer Bonn-Miller, Marcel O. TI Changes in facets of mindfulness and posttraumatic stress disorder treatment outcome SO PSYCHIATRY RESEARCH LA English DT Article DE Mindfulness; Posttraumatic Stress Disorder; PTSD; Acceptance; Awareness; Treatment outcome ID COGNITIVE-PROCESSING THERAPY; CLINICAL-SIGNIFICANCE; EMOTION REGULATION; SELF-REPORT; DEPRESSION; VETERANS; INVENTORY; EXPOSURE; VICTIMS; SKILLS AB Though there has been a recent surge of interest in the relations between facets of mindfulness and Posttraumatic Stress Disorder (PTSD), there has been a dearth of empirical studies investigating the impact of changes in facets of mindfulness on PTSD treatment outcomes. The present study tested the prospective associations between pre- to post-treatment changes in facets of mindfulness and PTSD and depression severity at treatment discharge, among 48 military Veterans in residential PTSD treatment adhering to a cognitive-behavioral framework. Together, changes in facets of mindfulness significantly explained post-treatment PTSD and depression severity (19-24% of variance). Changes in acting with awareness explained unique variance in post-treatment PTSD severity and changes in nonjudgmental acceptance explained unique variance in post-treatment depression severity. These results remained significant after adjusting for shared variance with length of treatment stay. Published by Elsevier Ireland Ltd. C1 [Boden, Matthew Tyler; Bonn-Miller, Marcel O.] Ctr Hlth Care Evaluat, Menlo Pk, CA USA. [Boden, Matthew Tyler; Walser, Robyn D.; Bui, Leena; Alvarez, Jennifer; Bonn-Miller, Marcel O.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Bernstein, Amit] Univ Haifa, Dept Psychol, IL-31999 Haifa, Israel. [Walser, Robyn D.; Bonn-Miller, Marcel O.] Natl Ctr PTSD, Menlo Pk, CA USA. [Bonn-Miller, Marcel O.] Philadelphia VA Med Ctr, Ctr Excellence Subst Abuse Treatment & Educ, Philadelphia, PA USA. RP Boden, MT (reprint author), 795 Willow Rd,152 MPD, Menlo Pk, CA 94025 USA. EM matthew.t.boden@gmail.com FU Israeli Council for Higher Education Yigal Alon Fellowship; European Union; Psychology Beyond Borders Mission Award; Rothschild-Caesarea Foundation's Returning Scientists Project at the University of Haifa; NIH Clinical LRP; Veterans Affairs Clinical Science Research and Development (CSR&D) Career Development Award; California HIV/AIDS Research Program IDEA Award [163836] FX Dr. Bernstein recognizes the funding support from the Israeli Council for Higher Education Yigal Alon Fellowship, the European Union FP-7 Marie Curie Fellowship International Reintegration Grant, Psychology Beyond Borders Mission Award, the Rothschild-Caesarea Foundation's Returning Scientists Project at the University of Haifa, and a NIH Clinical LRP. This work was also supported by a Veterans Affairs Clinical Science Research and Development (CSR&D) Career Development Award-2, and California HIV/AIDS Research Program IDEA Award (163836), Granted to Dr. Bonn-Miller. The expressed views do not necessarily represent those of the Department of Veterans Affairs. NR 28 TC 15 Z9 16 U1 7 U2 30 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD DEC 30 PY 2012 VL 200 IS 2-3 BP 609 EP 613 DI 10.1016/j.psychres.2012.07.011 PG 5 WC Psychiatry SC Psychiatry GA 073TF UT WOS:000313764700084 ER PT J AU Fried, R Surman, C Hammerness, P Petty, C Faraone, S Hyder, L Westerberg, D Small, J Corkum, L Claudat, K Biederman, J AF Fried, Ronna Surman, Craig Hammerness, Paul Petty, Carter Faraone, Stephen Hyder, Laran Westerberg, Diana Small, Jacqueline Corkum, Lyndsey Claudat, Kim Biederman, Joseph TI A controlled study of a simulated workplace laboratory for adults with attention deficit hyperactivity disorder SO PSYCHIATRY RESEARCH LA English DT Article DE Workplace; Employment; Adult ADHD; Self-report ID DEFICIT/HYPERACTIVITY DISORDER; COLLEGE-STUDENTS; PSYCHIATRIC STATUS; DOUBLE-BLIND; FOLLOW-UP; ADHD; PERFORMANCE; CHILDREN; QUESTIONNAIRE; ADOLESCENTS AB Despite an extant literature documenting that adults with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for significant difficulties in the workplace, there is little documentation of the underlying factors associated with these impairments. The main aim of this study was to examine specific deficiencies associated with ADHD on workplace performance in a simulated workplace laboratory relative to controls. Participants were 56 non-medicated young adults with DSM-IV ADHD and 63 age- and sex-matched controls without ADHD. Participants spent 10 h in a workplace simulation laboratory. Areas assessed included: (1) simulated tasks documented in a government report (SCANS) often required in workplace settings (taxing vigilance; planning; cooperation; attention to detail), (2) observer ratings, and (3) self-reports. Robust findings were found in the statistically significant differences on self-report of ADHD symptoms found between participants with ADHD and controls during all workplace tasks and periods of the workday. Task performance was found to be deficient in a small number of areas, and there were a few statistically significant differences identified by observer ratings. Symptoms reported by participants with ADHD in the simulation including internal restlessness, intolerance of boredom and difficulty maintaining vigilance were significant and could adversely impact workplace performance over the long-term. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Fried, Ronna; Surman, Craig; Hammerness, Paul; Petty, Carter; Hyder, Laran; Westerberg, Diana; Small, Jacqueline; Corkum, Lyndsey; Claudat, Kim; Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Boston, MA 02114 USA. [Surman, Craig; Hammerness, Paul; Biederman, Joseph] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Faraone, Stephen] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [Faraone, Stephen] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA. RP Fried, R (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Warren 705,55 Fruit St, Boston, MA 02114 USA. EM rfried@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NIH/NIMH [1R21MH081085-01] FX This study was funded NIH/NIMH 1R21MH081085-01; the NIMH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. We would like to acknowledge Dr. Eric Mick for statistical analysis of data in this study. NR 54 TC 4 Z9 4 U1 2 U2 15 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD DEC 30 PY 2012 VL 200 IS 2-3 BP 949 EP 956 DI 10.1016/j.psychres.2012.04.020 PG 8 WC Psychiatry SC Psychiatry GA 073TF UT WOS:000313764700138 PM 22608823 ER PT J AU Grubaugh, AL Tuerk, PW Egede, LE Frueh, BC AF Grubaugh, Anouk L. Tuerk, Peter W. Egede, Leonard E. Frueh, Bartley Christopher TI Perceptions of PTSD research participation among patients with severe mental illness SO PSYCHIATRY RESEARCH LA English DT Article DE Dual diagnosis; Patient participation; Human research subject protection AB Due to concerns that individuals with severe mental illness (SMI) are too fragile to participate in trauma/PTSD research, we examined reactions to PTSD research participation among these patients. Most patients viewed their participation favorably and were not significantly distressed, suggesting an adequate benefit of trauma/PTSD research participation in this population. Published by Elsevier Ireland Ltd. C1 [Grubaugh, Anouk L.; Tuerk, Peter W.] Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Grubaugh, Anouk L.; Tuerk, Peter W.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29401 USA. [Egede, Leonard E.] Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. [Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. [Frueh, Bartley Christopher] Univ Hawaii, Dept Psychol, Hilo, HI 96720 USA. [Frueh, Bartley Christopher] Menninger Clin, Houston, TX 77080 USA. RP Grubaugh, AL (reprint author), Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, 109 Bee St, Charleston, SC 29401 USA. EM grubaugh@musc.edu FU Veterans Affairs Health Services Research and Development [CD207015]; National Institute of Mental Health [MH074468] FX This work was partially supported by Grant CD207015 from Veterans Affairs Health Services Research and Development and by Grant MH074468 from the National Institute of Mental Health. NR 10 TC 7 Z9 7 U1 1 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD DEC 30 PY 2012 VL 200 IS 2-3 BP 1071 EP 1073 DI 10.1016/j.psychres.2012.07.039 PG 3 WC Psychiatry SC Psychiatry GA 073TF UT WOS:000313764700161 PM 22884217 ER PT J AU Anand, S Ortel, BJ Pereira, SP Hasan, T Maytin, EV AF Anand, Sanjay Ortel, Bernhard J. Pereira, Stephen P. Hasan, Tayyaba Maytin, Edward V. TI Biomodulatory approaches to photodynamic therapy for solid tumors SO CANCER LETTERS LA English DT Review DE ALA; PDT; Vitamin D; Differentiation; Porphyrin ID VULVAL INTRAEPITHELIAL NEOPLASIA; PROTOPORPHYRIN IX ACCUMULATION; HEART-TRANSPLANT RECIPIENTS; PROSTATE-CANCER CELLS; IRON-CHELATING AGENT; HIGH-GRADE DYSPLASIA; AMINOLEVULINIC ACID; BARRETTS-ESOPHAGUS; SKIN-CANCER; IN-VIVO AB Photodynamic Therapy (PDT) uses a photosensitizing drug in combination with visible light to kill cancer cells. PDT has an advantage over surgery or ionizing radiation because PDT can eliminate tumors without causing fibrosis or scarring. Disadvantages include the dual need for drug and light, and a generally lower efficacy for PDT vs. surgery. This minireview describes basic principles of PDT, photosensitizers available, and aspects of tumor biology that may provide further opportunities for treatment optimization. An emerging biomodulatory approach, using methotrexate or Vitamin D in combination with aminolevulinate-based PDT, is described. Finally, current clinical uses of PDT for solid malignancies are reviewed. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Anand, Sanjay; Maytin, Edward V.] Cleveland Clin, Dept Dermatol, Cleveland, OH 44195 USA. [Anand, Sanjay; Maytin, Edward V.] Cleveland Clin, Lerner Res Inst, Cleveland, OH 44195 USA. [Ortel, Bernhard J.] Univ Chicago, Dermatol Sect, Chicago, IL 60637 USA. [Pereira, Stephen P.] UCL, UCL Inst Liver & Digest Hlth, London, England. [Hasan, Tayyaba; Maytin, Edward V.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Maytin, EV (reprint author), Cleveland Clin, Dept Dermatol, Mailstop ND-20,9500 Euclid Ave, Cleveland, OH 44195 USA. EM maytine@ccf.org FU National Cancer Institute/NIH [P01-CA84203] FX The authors would like to acknowledge Grant P01-CA84203 from the National Cancer Institute/NIH, which supported much of the work they performed as reviewed in this article. NR 91 TC 56 Z9 57 U1 2 U2 63 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD DEC 29 PY 2012 VL 326 IS 1 BP 8 EP 16 DI 10.1016/j.canlet.2012.07.026 PG 9 WC Oncology SC Oncology GA 015ZJ UT WOS:000309486600002 PM 22842096 ER PT J AU Cartana, T Saftoiu, A Gruionu, LG Gheonea, DI Pirici, D Georgescu, CV Ciocalteu, A Gruionu, G AF Cartana, Tatiana Saftoiu, Adrian Gruionu, Lucian Gheorghe Gheonea, Dan Ionut Pirici, Daniel Georgescu, Claudia Valentina Ciocalteu, Adriana Gruionu, Gabriel TI Confocal Laser Endomicroscopy for the Morphometric Evaluation of Microvessels in Human Colorectal Cancer Using Targeted Anti-CD31 Antibodies SO PLOS ONE LA English DT Article ID GROWTH-FACTOR-RECEPTOR; IN-VIVO; TUMOR ANGIOGENESIS AB Introduction: Numerous anti-angiogenic agents are currently developed to limit tumor growth and metastasis. While these drugs offer hope for cancer patients, their transient effect on tumor vasculature is difficult to assess in clinical settings. Confocal laser endomicroscopy (CLE) is a novel endoscopic imaging technology that enables histological examination of the gastrointestinal mucosa. The aim of the present study was to evaluate the feasibility of using CLE to image the vascular network in fresh biopsies of human colorectal tissue. For this purpose we have imaged normal and malignant biopsy tissue samples and compared the vascular network parameters obtained with CLE with established histopathology techniques. Materials and Methods: Fresh non-fixed biopsy samples of both normal and malignant colorectal mucosa were stained with fluorescently labeled anti-CD31 antibodies and imaged by CLE using a dedicated endomicroscopy system. Corresponding biopsy samples underwent immunohistochemical staining for CD31, assessing the microvessel density (MVD) and vascular areas for comparison with CLE data, which were measured offline using specific software. Results: The vessels were imaged by CLE in both normal and tumor samples. The average diameter of normal vessels was 8.5 +/- 0.9 mu m whereas in tumor samples it was 13.5 +/- 0.7 mu m (p = 0.0049). Vascular density was 188.7 +/- 24.9 vessels/mm(2) in the normal tissue vs. 242.4 +/- 16.1 vessels/mm(2) in the colorectal cancer samples (p = 0.1201). In the immunohistochemistry samples, the MVD was 211.2 +/- 42.9/mm(2) and 351.3 +/- 39.6/mm(2) for normal and malignant mucosa, respectively. The vascular area was 2.9 +/- 0.5% of total tissue area for the normal mucosa and 8.5 +/- 2.1% for primary colorectal cancer tissue. Conclusion: Selective imaging of blood vessels with CLE is feasible in normal and tumor colorectal tissue by using fluorescently labeled antibodies targeted against an endothelial marker. The method could be translated into the clinical setting for monitoring of anti-angiogenic therapy. C1 [Cartana, Tatiana; Saftoiu, Adrian; Gruionu, Lucian Gheorghe; Gheonea, Dan Ionut; Ciocalteu, Adriana; Gruionu, Gabriel] Univ Med & Pharm Craiova, Res Ctr Gastroenterol & Hepatol, Craiova, Romania. [Gruionu, Lucian Gheorghe] Univ Craiova, Dept Mech Engn, Craiova, Romania. [Pirici, Daniel] Univ Med & Pharm Craiova, Dept Histol, Craiova, Romania. [Georgescu, Claudia Valentina] Emergency Cty Hosp, Dept Pathol, Craiova, Romania. [Gruionu, Gabriel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Steele Lab Tumor Biol,Dept Radiat Oncol, Boston, MA USA. RP Saftoiu, A (reprint author), Univ Med & Pharm Craiova, Res Ctr Gastroenterol & Hepatol, Craiova, Romania. EM adrian.saftoiu@webmail.umfcv.ro RI Gheonea, Dan Ionut/C-3578-2012; Saftoiu, Adrian/C-2792-2011; Gruionu, Lucian/F-6121-2011; OI Gruionu, Lucian/0000-0002-4526-0864; Pirici, Daniel/0000-0002-0196-0949; Pirici, Daniel/0000-0001-9192-7319 FU National Research Council (CNCS), Romania [PN-II-ID-PCE-2011-3-0664] FX This work was supported from the research grant entitled "Clinical and Biomathematical Modeling of Vascular Changes Following Anti-Angiogenic Therapy in Advanced Colorectal Carcinoma", funded by the National Research Council (CNCS), Romania, contract number PN-II-ID-PCE-2011-3-0664. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 23 TC 11 Z9 12 U1 1 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 28 PY 2012 VL 7 IS 12 AR e52815 DI 10.1371/journal.pone.0052815 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 064DQ UT WOS:000313051500065 PM 23285192 ER PT J AU Harris, RS Fujii-Rios, H Winkler, T Musch, G Melo, MFV Venegas, JG AF Harris, R. Scott Fujii-Rios, Hanae Winkler, Tilo Musch, Guido Melo, Marcos F. Vidal Venegas, Jose G. TI Ventilation Defect Formation in Healthy and Asthma Subjects Is Determined by Lung Inflation SO PLOS ONE LA English DT Article ID HE-3 MAGNETIC-RESONANCE; REGIONAL VENTILATION; PULMONARY PERFUSION; BRONCHOCONSTRICTION; METHACHOLINE; PET; DYSFUNCTION; HISTAMINE; RESPONSES; PATCHY AB Background: Imaging studies have demonstrated that ventilation during bronchoconstriction in subjects with asthma is patchy with large ventilation defective areas (Vdefs). Based on a theoretical model, we postulated that during bronchoconstriction, as smooth muscle force activation increases, a patchy distribution of ventilation should emerge, even in the presence of minimal heterogeneity the lung. We therefore theorized that in normal lungs, Vdefs should also emerge in regions of the lung with reduced expansion. Objective: We studied 12 healthy subjects to evaluate whether Vdefs formed during bronchoconstriction, and compared their Vdefs with those observed in 9 subjects with mild asthma. Methods: Spirometry, low frequency (0.15 Hz) lung elastance and resistance, and regional ventilation by intravenous (NN)-N-13-saline positron emission tomography were measured before and after a challenge with nebulized methacholine. Vdefs were defined as regions with elevated residual (NN)-N-13 after a period of washout. The average location, ventilation, volume, and fractional gas content of the Vdefs, relative to those of the rest of the lung, were calculated for both groups. Results: Consistent with the predictions of the theoretical model, both healthy subjects and those with asthma developed Vdefs. These Vdefs tended to form in regions that, at baseline, had a lower degree of lung inflation and, in healthy subjects, tended to occur in more dependent locations than in subjects with asthma. Conclusion: The formation of Vdefs is determined by the state of inflation prior to bronchoconstriction. C1 [Harris, R. Scott; Fujii-Rios, Hanae] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Harris, R. Scott; Fujii-Rios, Hanae; Winkler, Tilo; Musch, Guido; Melo, Marcos F. Vidal; Venegas, Jose G.] Harvard Univ, Sch Med, Boston, MA USA. RP Harris, RS (reprint author), Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. EM rsharris@mgh.harvard.edu RI Winkler, Tilo/B-5337-2009 OI Winkler, Tilo/0000-0002-7276-5550 FU National Institutes of Health [HL-68011, HL-04501] FX This work was supported by grants from the National Institutes of Health: HL-68011 to JGV and HL-04501 to RSH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 26 TC 8 Z9 8 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 28 PY 2012 VL 7 IS 12 AR e53216 DI 10.1371/journal.pone.0053216 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 064DQ UT WOS:000313051500124 PM 23285270 ER PT J AU Mittal, N AF Mittal, Nikhil TI Cell Surface Concentrations and Concentration Ranges for Testing In Vitro Autocrine Loops and Small Molecules SO PLOS ONE LA English DT Article ID EMBRYONIC STEM-CELLS; TRANSPORT; BIOMARKER; SURVIVAL; ASSAYS; LIGAND; SERUM; MODEL AB A common assumption made when performing in vitro cellular assays is that the concentration of substances in the culture system is uniform. However, since the cells that internalize and secrete substances reside at the bottom of the well, it is conceivable that a concentration gradient could arise across the fluid layer. Importantly, the concentration of a substance in the vicinity of a cell, which is the concentration of interest, cannot be measured via existing methods. In this work a simple strategy for estimating the concentration of a chemical species at the surface of a cell is presented. Finally, this result is used to outline a method for determining the appropriate concentration ranges for testing in vitro autocrine loops and small molecules. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Mittal, N (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. EM nvmittal@partners.org OI Mittal, Nikhil/0000-0002-2360-7134 NR 18 TC 0 Z9 0 U1 1 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 28 PY 2012 VL 7 IS 12 AR e51796 DI 10.1371/journal.pone.0051796 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 064DQ UT WOS:000313051500014 PM 23284769 ER PT J AU Dominy, JE Lee, Y Jedrychowski, MP Chim, H Jurczak, MJ Camporez, JP Ruan, HB Feldman, J Pierce, K Mostoslavsky, R Denu, JM Clish, CB Yang, XY Shulman, GI Gygi, SP Puigserver, P AF Dominy, John E., Jr. Lee, Yoonjin Jedrychowski, Mark P. Chim, Helen Jurczak, Michael J. Camporez, Joao Paulo Ruan, Hai-Bin Feldman, Jessica Pierce, Kerry Mostoslavsky, Raul Denu, John M. Clish, Clary B. Yang, Xiaoyong Shulman, Gerald I. Gygi, Steven P. Puigserver, Pere TI The Deacetylase Sirt6 Activates the Acetyltransferase GCN5 and Suppresses Hepatic Gluconeogenesis SO MOLECULAR CELL LA English DT Article ID FATTY-ACID OXIDATION; TRANSCRIPTIONAL COACTIVATOR; GLUCOSE-HOMEOSTASIS; INSULIN-RESISTANCE; PGC-1-ALPHA; METABOLISM; COMPLEX; KINASE; LIVER; PGC-1 AB Hepatic glucose production (HGP) maintains blood glucose levels during fasting but can also exacerbate diabetic hyperglycemia. HGP is dynamically controlled by a signaling/transcriptional network that regulates the expression/activity of gluconeogenic enzymes. A key mediator of gluconeogenic gene transcription is PGC-1 alpha. PGC-1 alpha's activation of gluconeogenic gene expression is dependent upon its acetylation state, which is controlled by the acetyltransferase GCN5 and the deacetylase Sirt1. Nevertheless, whether other chromatin modifiers-particularly other sirtuins-can modulate PGC-1 alpha acetylation is currently unknown. Herein, we report that Sirt6 strongly controls PGC-1 alpha acetylation. Surprisingly, Sirt6 induces PGC-1 alpha acetylation and suppresses HGP. Sirt6 depletion decreases PGC-1 alpha acetylation and promotes HGP. These acetylation effects are GCN5 dependent: Sirt6 interacts with and modifies GCN5, enhancing GCN5's activity. Lepr(db/db) mice, an obese/diabetic animal model, exhibit reduced Sirt6 levels; ectopic re-expression suppresses gluconeogenic genes and normalizes glycemia. Activation of hepatic Sirt6 may therefore be therapeutically useful for treating insulin-resistant diabetes. C1 [Dominy, John E., Jr.; Lee, Yoonjin; Chim, Helen; Puigserver, Pere] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Dominy, John E., Jr.; Lee, Yoonjin; Jedrychowski, Mark P.; Chim, Helen; Gygi, Steven P.; Puigserver, Pere] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Lee, Yoonjin] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Jurczak, Michael J.; Camporez, Joao Paulo; Ruan, Hai-Bin; Yang, Xiaoyong; Shulman, Gerald I.] Yale Univ, Sch Med, Yale Mouse Metab Phenotyping Ctr, New Haven, CT 06510 USA. [Jurczak, Michael J.; Camporez, Joao Paulo; Ruan, Hai-Bin; Yang, Xiaoyong; Shulman, Gerald I.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Jurczak, Michael J.; Camporez, Joao Paulo; Ruan, Hai-Bin; Yang, Xiaoyong; Shulman, Gerald I.] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA. [Feldman, Jessica; Denu, John M.] Univ Wisconsin, Dept Biomol Chem, Madison, WI 53715 USA. [Pierce, Kerry; Clish, Clary B.] Broad Inst MIT & Harvard, Metabolite Profiling Initiat, Cambridge, MA 02142 USA. [Mostoslavsky, Raul] Harvard Univ, Sch Med, Ctr Canc, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Puigserver, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM pere_puigserver@dfci.harvard.edu RI Ruan, Hai-Bin/G-9907-2012; Camporez, Joao Paulo/B-9122-2015; OI Ruan, Hai-Bin/0000-0002-3858-1272; Jurczak, Michael/0000-0002-6335-6915 FU National Institutes of Health; Ewha Womans University; DFCI; American Diabetes Association; NIH/NIDDK [RO1 069966]; NIH [DK059635]; Department of Defense FX We thank members of the Puigserver lab for important discussions about this project. J.E.D. was supported in part by an NRSA Kirschstein fellowship from the National Institutes of Health and Y.L. was supported in part by a 21st Century Leaders scholarship from Ewha Womans University. Research was supported with funds from the DFCI and with grants from the American Diabetes Association, Department of Defense, and NIH/NIDDK (RO1 069966) awarded to P.P., as well as with a grant from NIH (DK059635) awarded to Yale's Mouse Metabolic Phenotyping Center/G.I.S. NR 31 TC 72 Z9 72 U1 1 U2 24 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD DEC 28 PY 2012 VL 48 IS 6 BP 900 EP 913 DI 10.1016/j.molcel.2012.09.030 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 066OQ UT WOS:000313230500009 PM 23142079 ER PT J AU Petrella, BL Armstrong, DA Vincenti, MP AF Petrella, Brenda L. Armstrong, David A. Vincenti, Matthew P. TI Interleukin-1 beta and transforming growth factor-beta 3 cooperate to activate matrix metalloproteinase expression and invasiveness in A549 lung adenocarcinoma cells SO CANCER LETTERS LA English DT Article DE Carcinoma; Non-small-cell lung; Interleukin-1beta; Transforming growth factor beta; Matrix metalloproteinases ID NF-KAPPA-B; SIGNAL-TRANSDUCTION; CANCER CELLS; PROMOTES; INFLAMMATION; TRANSITION; PATHWAYS; MUTATION AB Cytokines present in the tumor microenvironment can promote the invasiveness and metastatic potential of cancer cells. We therefore investigated the effects of interleukin-1 beta (IL-1B) and transforming growth factor beta-3 (TGFB3) on the non-small cell lung carcinoma (NSCLC) cell line A549. We found that these cytokines synergistically activated matrix metalloproteinase (MMP)-1, MMP-3, and MMP-10 gene expression in these cells through mitogen-activated protein kinase (MAPK)-dependent pathways. Consistent with this, both cytokines stimulated epithelial to mesenchymal transition and MAPK-dependent invasion through Matrigel (TM). These studies identify IL-1B and TGFB3 as pro-invasive factors in NSCLC and potential therapeutic targets for tumor progression. Published by Elsevier Ireland Ltd. C1 [Petrella, Brenda L.; Vincenti, Matthew P.] US Dept Vet Affairs, Res Serv, White River Jct, VT 05009 USA. [Petrella, Brenda L.; Vincenti, Matthew P.] Geisel Sch Med Dartmouth, Dept Med, Lebanon, NH USA. [Armstrong, David A.] Geisel Sch Med Dartmouth, Dept Pharmacol, Hanover, NH USA. RP Vincenti, MP (reprint author), VA Med Ctr, Bldg 44,Room 2-117,215 N Main St, White River Jct, VT 05009 USA. EM Matthew.P.Vincenti@dartmouth.edu FU VA Career Development Award; VA Merit Review Award FX Funding from a VA Career Development Award (BLP) and from a VA Merit Review Award (MPV) supported this research. NR 21 TC 17 Z9 17 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD DEC 28 PY 2012 VL 325 IS 2 BP 220 EP 226 DI 10.1016/j.canlet.2012.07.009 PG 7 WC Oncology SC Oncology GA 007QZ UT WOS:000308904500013 PM 22796605 ER PT J AU Christie, D Shofer, J Millard, SP Li, E DeMichele-Sweet, MA Weamer, EA Kamboh, MI Lopez, OL Sweet, RA Tsuang, D AF Christie, Drew Shofer, Jane Millard, Steven P. Li, Ellen DeMichele-Sweet, Mary Ann Weamer, Elise A. Kamboh, M. Ilyas Lopez, Oscar L. Sweet, Robert A. Tsuang, Debby TI Genetic association between APOE*4 and neuropsychiatric symptoms in patients with probable Alzheimer's disease is dependent on the psychosis phenotype SO BEHAVIORAL AND BRAIN FUNCTIONS LA English DT Article DE Alzheimer's disease; Apolipoprotein E; Genetics; Behavior; Hallucinations ID BEHAVIOR RATING-SCALE; DEMENTIA; DELUSIONS AB Background: Neuropsychiatric symptoms such as psychosis are prevalent in patients with probable Alzheimer's disease (AD) and are associated with increased morbidity and mortality. Because these disabling symptoms are generally not well tolerated by caregivers, patients with these symptoms tend to be institutionalized earlier than patients without them. The identification of protective and risk factors for neuropsychiatric symptoms in AD would facilitate the development of more specific treatments for these symptoms and thereby decrease morbidity and mortality in AD. The E4 allele of the apolipoprotein E (APOE) gene is a well-documented risk factor for the development of AD. However, genetic association studies of the APOE 4 allele and BPS in AD have produced conflicting findings. Methods: This study investigates the association between APOE and neuropsychiatric symptoms in a large sample of clinically well-characterized subjects with probable AD (n=790) who were systematically evaluated using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Behavioral Rating Scale for Dementia (BRSD). Results: Our study found that hallucinations were significantly more likely to occur in subjects with no APOE4 alleles than in subjects with two E4 alleles (15% of subjects and 5% of subjects, respectively; p=.0066), whereas there was no association between the occurrence of delusions, aberrant motor behavior, or agitation and the number of E4 alleles. However, 94% of the subjects with hallucinations also had delusions (D+H). Conclusion: These findings suggest that in AD the E4 allele is differentially associated with D+H but not delusions alone. This is consistent with the hypothesis that distinct psychotic subphenotypes may be associated with the APOE allele. C1 [Christie, Drew; Shofer, Jane; Millard, Steven P.] VISN 20 Mental Illness, Seattle, WA USA. [Tsuang, Debby] Educ Ctr, Seattle, WA USA. [Tsuang, Debby] Ctr Clin, Seattle, WA USA. [DeMichele-Sweet, Mary Ann; Sweet, Robert A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Weamer, Elise A.; Lopez, Oscar L.; Sweet, Robert A.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Kamboh, M. Ilyas] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. [Li, Ellen; Sweet, Robert A.] VA Pittsburgh Healthcare Syst, Res Educ & Clin Ctr, VISN Mental Illness 4, Pittsburgh, PA USA. [Tsuang, Debby] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Tsuang, D (reprint author), Geriatr Res Ctr, Seattle, WA USA. EM dwt1@uw.edu RI Tsuang, Debby/L-7234-2016; OI Tsuang, Debby/0000-0002-4716-1894; Kamboh, M. Ilyas/0000-0002-3453-1438 FU US Department of Veterans Affairs Office of Research and Development Biomedical Laboratory Research Program [1I01BX000531]; NIH [NS48595, NS065070, NS062684, AG06781, AG10845, AG05136, AG05133, AG028383, AG008017, AG027224, AG10124, AG030653] FX This material is based upon work supported in part by the US Department of Veterans Affairs Office of Research and Development Biomedical Laboratory Research Program (Merit Review 1I01BX000531). It is also supported by NIH grants NS48595, NS065070, NS062684, AG06781, AG10845, AG05136, AG05133, AG028383, AG008017, AG027224, AG10124, and AG030653. The authors wish to thank Andrew David for his expert editorial assistance. NR 19 TC 5 Z9 6 U1 2 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1744-9081 J9 BEHAV BRAIN FUNCT JI Behav. Brain Funct. PD DEC 27 PY 2012 VL 8 AR 62 DI 10.1186/1744-9081-8-62 PG 7 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 074DW UT WOS:000313793800001 PM 23270420 ER PT J AU Prelack, K Dwyer, J Ziegler, P Kehayias, JJ AF Prelack, Kathy Dwyer, Johanna Ziegler, Paula Kehayias, Joseph J. TI Bone mineral density in elite adolescent female figure skaters SO JOURNAL OF THE INTERNATIONAL SOCIETY OF SPORTS NUTRITION LA English DT Article ID BODY-COMPOSITION; ATHLETE TRIAD; YOUNG-WOMEN; ENERGY; OSTEOPOROSIS; DIAGNOSIS; CHILDREN; WEIGHT; SPORTS; MASS AB Elite adolescent figure skaters must accommodate both the physical demands of competitive training and the accelerated rate of bone growth that is associated with adolescence, in this sport that emphasizes leanness. Although, these athletes apparently have sufficient osteogenic stimuli to mitigate the effects of possible low energy availability on bone health, the extent or magnitude of bone accrual also varies with training effects, which differ among skater disciplines. Purpose: We studied differences in total and regional bone mineral density in 36 nationally ranked skaters among 3 skater disciplines: single, pairs, and dancers. Methods: Bone mineral density (BMD) of the total body and its regions was measured by dual energy x-ray absorptiometry (DXA). Values for total body, spine, pelvis and leg were entered into a statistical mixed regression model to identify the effect of skater discipline on bone mineralization while controlling for energy, vitamin D, and calcium intake. Results: The skaters had a mean body mass index of 19.8 +/- 2.1 and % fat mass of 19.2 +/- 5.8. After controlling for dietary intakes of energy, calcium, and vitamin D, there was a significant relationship between skater discipline and BMD (p = 0.002), with single skaters having greater BMD in the total body, legs, and pelvis than ice dancers (p < 0.001). Pair skaters had greater pelvic BMD than ice dancers (p = 0.001). Conclusions: Single and pair skaters have greater BMD than ice dancers. The osteogenic effect of physical training is most apparent in single skaters, particularly in the bone loading sites of the leg and pelvis. C1 [Prelack, Kathy] Hosp Children, Shriners, Boston, MA 02114 USA. [Prelack, Kathy] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Prelack, Kathy] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [Dwyer, Johanna] Tufts Med Ctr, Frances Stern Nutr Ctr, Boston, MA 02111 USA. [Dwyer, Johanna] Tufts Univ, Jean Mayer Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Dwyer, Johanna] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Ziegler, Paula] Coll St Elizabeth, Morristown, NJ 07960 USA. [Kehayias, Joseph J.] Tufts Univ, Body Composit Lab, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. RP Prelack, K (reprint author), Hosp Children, Shriners, 51 Blossom St, Boston, MA 02114 USA. EM kprelack@shrinenet.org OI Dwyer, Johanna/0000-0002-0783-1769 FU U.S. Department of Agriculture Cooperative State Research Education Extension [2006-35200-17259]; USDA Agricultural Research Service [58 1950-7-707]; Gerber Products Company FX This work was supported in part by funds provided by the U.S. Department of Agriculture Cooperative State Research Education & Extension with grant #2006-35200-17259 and USDA Agricultural Research Service under agreement No 58 1950-7-707. Any opinions, findings, conclusions or recommendations expressed are those of the authors and do not reflect the view of the US Department of Agriculture. This study was also supported by a non-restricted grant to Tufts University from the Gerber Products Company. NR 25 TC 2 Z9 2 U1 4 U2 26 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1550-2783 J9 J INT SOC SPORT NUTR JI J. Int. Soc. Sport Nutr. PD DEC 27 PY 2012 VL 9 AR 57 DI 10.1186/1550-2783-9-57 PG 6 WC Nutrition & Dietetics; Sport Sciences SC Nutrition & Dietetics; Sport Sciences GA 072BQ UT WOS:000313643700001 PM 23270306 ER PT J AU Weiner, J Scalea, J Ishikawa, Y Okumi, M Griesemer, A Hirakata, A Etter, J Gillon, B Moran, S Shimizu, A Yamada, K Sachs, DH AF Weiner, Joshua Scalea, Joseph Ishikawa, Yoshinori Okumi, Masayoshi Griesemer, Adam Hirakata, Atsushi Etter, Justin Gillon, Bradford Moran, Shannon Shimizu, Akira Yamada, Kazuhiko Sachs, David H. TI Tolerogenicity of Donor Major Histocompatibility Complex-Matched Skin Grafts in Previously Tolerant Massachusetts General Hospital Miniature Swine SO TRANSPLANTATION LA English DT Article DE Tolerance; Allografts; Miniature swine; MHC class I; Kidney transplantation ID MISMATCHED RENAL-ALLOGRAFTS; REGULATORY T-CELLS; PERIPHERAL-BLOOD LYMPHOCYTES; CLASS-I; TRANSPLANTATION TOLERANCE; INDIRECT RECOGNITION; KIDNEY ALLOGRAFTS; INDUCTION; ANTIGEN; MAINTENANCE AB Background. Long-term tolerance of class I disparate renal allografts in miniature swine can be induced by a short course of cyclosporine and persists for 3 to 4 months after grafts are removed. Donor class I peptide immunization 6 weeks after graftectomy of tolerated kidneys leads to sensitization, but donor skin grafts do not. Here, we tested the hypothesis that skin grafts prevent rejection after simultaneous peptide administration and skin grafting. Methods. Miniature swine underwent bilateral nephrectomy and class I-mismatched renal transplantation with a 12-day course of cyclosporine A to induce long-term tolerance. Tolerated allografts were then replaced with recipient-matched kidneys, and animals were challenged with simultaneous donor-type skin grafts and peptide. Six weeks later, second donor-matched kidneys were transplanted without immunosuppression, and immune responses were characterized. Results. Animals treated only with peptide (n=2) rejected subsequent renal transplants in 3 to 5 days with strong in vitro antidonor responses. Of five recipients of skin-plus-peptide regimen, two accepted kidneys long term, one demonstrated a modestly prolonged survival (11 days), and two rejected rapidly (5-7 days). The two long-term acceptors maintained donor-specific hyporesponsiveness in vitro. Conclusions. Sensitization by class I peptide in previously tolerant swine could be prevented by simultaneous class I skin grafts. These data suggest that skin grafts may actually augment rather than abrogate downregulation in some cases. A mechanistic hypothesis for this surprising result is that recognition of class I antigens through the direct rather than the indirect pathway of antigen presentation promotes tolerance by expanding regulatory T cells. C1 [Weiner, Joshua; Scalea, Joseph; Ishikawa, Yoshinori; Okumi, Masayoshi; Griesemer, Adam; Hirakata, Atsushi; Etter, Justin; Gillon, Bradford; Moran, Shannon; Shimizu, Akira; Yamada, Kazuhiko; Sachs, David H.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Sachs, DH (reprint author), Massachusetts Gen Hosp E, Transplantat Biol Res Ctr, Bldg 149,13th St,Ste 9019, Charlestown, MA 02129 USA. EM david.sachs@tbrc.mgh.harvard.edu FU National Institute of Allergy and Infectious Disease [R37AI031046]; Howard Hughes Medical Institute FX This project was supported by R37AI031046 from the National Institute of Allergy and Infectious Disease and the Howard Hughes Medical Institute. NR 45 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD DEC 27 PY 2012 VL 94 IS 12 BP 1192 EP 1199 DI 10.1097/TP.0b013e31827254f5 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 062JQ UT WOS:000312916500004 PM 23269447 ER PT J AU Vegfors, J Petersson, S Kovacs, A Polyak, K Enerback, C AF Vegfors, Jenny Petersson, Stina Kovacs, Aniko Polyak, Kornelia Enerback, Charlotta TI The Expression of Psoriasin (S100A7) and CD24 Is Linked and Related to the Differentiation of Mammary Epithelial Cells SO PLOS ONE LA English DT Article ID CARCINOMA IN-SITU; HUMAN BREAST-CARCINOMA; DUCTAL CARCINOMA; CANCER DEVELOPMENT; CALGRANULIN-B; PROGRESSION; GROWTH; PROTEINS; RECEPTOR; CULTURE AB Psoriasin (S100A7), a member of the S100 family of calcium-binding proteins, is highly expressed in high-grade ductal carcinoma in situ (DCIS) and in the benign hyperproliferative skin disorder psoriasis. The gene that encodes psoriasin and many other S100 genes are located within a gene cluster on chromosome region 1q21, known as the epidermal differentiation complex. This cluster contains genes for several differentiation markers that play important roles in the terminal differentiation of the epidermis. The purpose of the present study was to evaluate the role of psoriasin in the differentiation process of mammary epithelial cells. Normal mammary epithelial cells (MCF10A) cultured in confluence and suspension, conditions known to induce psoriasin expression, demonstrated a shift towards a more differentiated phenotype indicated by an increase in the expression of the luminal differentiation markers CD24 and MUC1 and the reduced expression of the breast stem cell marker CD44. The expression of psoriasin and MUC1 was most pronounced in the CD24(+)-enriched fraction of confluent MCF10A cells. The shift towards a more differentiated phenotype was abolished upon the downregulation of psoriasin using short hairpin RNA (shRNA) and small interfering RNA (siRNA). Using specific inhibitors, we showed that psoriasin and CD24 expression was regulated by reactive oxygen species (ROS) and the nuclear factor (NF)-kappa B signaling pathways. While immunohistochemical analyses of DCIS showed heterogeneity, the expression of psoriasin and CD24 showed a similar staining pattern. Our findings suggest that the expression of psoriasin is linked to the luminal differentiation marker CD24 in mammary epithelial cells. Psoriasin demonstrated an essential role in the shift towards a more differentiated CD24(+) phenotype, supporting the hypothesis that psoriasin plays a role in the differentiation of luminal mammary epithelial cells. C1 [Vegfors, Jenny; Petersson, Stina; Enerback, Charlotta] Linkoping Univ, Ingrid Asp Psoriasis Res Ctr, Dept Clin & Expt Med, Linkoping, Sweden. [Kovacs, Aniko] Sahlgrens Univ Hosp, Dept Pathol, Gothenburg, Sweden. [Polyak, Kornelia] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Enerback, C (reprint author), Linkoping Univ, Ingrid Asp Psoriasis Res Ctr, Dept Clin & Expt Med, Linkoping, Sweden. EM charlotta.enerback@liu.se FU Ingrid Asp Foundation; Swedish Cancer Society; Swedish Psoriasis Association; Welander Foundation FX This study was supported by grants from the Ingrid Asp Foundation, the Swedish Cancer Society, the Swedish Psoriasis Association and the Welander Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 41 TC 7 Z9 7 U1 0 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 27 PY 2012 VL 7 IS 12 AR e53119 DI 10.1371/journal.pone.0053119 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 061EA UT WOS:000312829100122 PM 23300877 ER PT J AU Metzger, ML Billett, A Link, MP AF Metzger, Monika L. Billett, Amy Link, Michael P. TI The Impact of Drug Shortages on Children with Cancer - The Example of Mechlorethamine SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID UNITED-STATES C1 [Metzger, Monika L.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Metzger, Monika L.] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA. [Billett, Amy] Dana Farber Canc Inst, Boston, MA 02115 USA. [Billett, Amy] Boston Childrens Hosp, Boston, MA USA. [Link, Michael P.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Link, Michael P.] Lucile Packard Childrens Hosp, Stanford, CA USA. RP Metzger, ML (reprint author), St Jude Childrens Res Hosp, 332 N Lauderdale St, Memphis, TN 38105 USA. NR 3 TC 20 Z9 20 U1 0 U2 10 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 27 PY 2012 VL 367 IS 26 BP 2461 EP 2463 DI 10.1056/NEJMp1212468 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 059OG UT WOS:000312714200001 PM 23268661 ER PT J AU Ecker, JL Solt, K Fitzsimons, MG MacGillivray, TE AF Ecker, Jeffrey L. Solt, Ken Fitzsimons, Michael G. MacGillivray, Thomas E. TI Case 40-2012: A 43-Year-Old Woman with Cardiorespiratory Arrest after a Cesarean Section SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID AMNIOTIC-FLUID EMBOLISM; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; DIAGNOSIS; MORTALITY C1 [Ecker, Jeffrey L.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Solt, Ken] Massachusetts Gen Hosp, Div Obstetr Anesthesia, Boston, MA 02114 USA. [Fitzsimons, Michael G.] Massachusetts Gen Hosp, Div Cardiac Anesthesia, Boston, MA 02114 USA. [MacGillivray, Thomas E.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [MacGillivray, Thomas E.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Ecker, Jeffrey L.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Solt, Ken; Fitzsimons, Michael G.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. [MacGillivray, Thomas E.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Ecker, JL (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. OI Solt, Ken/0000-0001-5328-2062 NR 21 TC 12 Z9 14 U1 1 U2 13 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 27 PY 2012 VL 367 IS 26 BP 2528 EP 2536 DI 10.1056/NEJMcpc1201413 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 059OG UT WOS:000312714200012 PM 23268668 ER PT J AU Batra, RK Hoo, GWS AF Batra, Raj K. Hoo, Guy W. Soo TI Reprogrammed Cells for Respiratory Papillomatosis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID THERAPY C1 [Batra, Raj K.; Hoo, Guy W. Soo] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Batra, RK (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. EM guy.soohoo@va.gov OI Batra, Raj K./0000-0002-1126-543X NR 5 TC 0 Z9 0 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 27 PY 2012 VL 367 IS 26 BP 2553 EP 2554 DI 10.1056/NEJMc1212926 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 059OG UT WOS:000312714200021 PM 23268676 ER PT J AU Hatcher, AM Tsai, AC Kumbakumba, E Dworkin, SL Hunt, PW Martin, JN Clark, G Bangsberg, DR Weiser, SD AF Hatcher, Abigail M. Tsai, Alexander C. Kumbakumba, Elias Dworkin, Shari L. Hunt, Peter W. Martin, Jeffrey N. Clark, Gina Bangsberg, David R. Weiser, Sheri D. TI Sexual Relationship Power and Depression among HIV-Infected Women in Rural Uganda SO PLOS ONE LA English DT Article ID LEARNED HELPLESSNESS MODEL; INTIMATE PARTNER VIOLENCE; MIDDLE-INCOME COUNTRIES; MENTAL-HEALTH-SERVICES; QUALITY-OF-LIFE; CD4 CELL COUNT; SOUTH-AFRICA; GENDER-DIFFERENCES; MEDICAL OUTCOMES; POSITIVE WOMEN AB Background: Depression is associated with increased HIV transmission risk, increased morbidity, and higher risk of HIV-related death among HIV-infected women. Low sexual relationship power also contributes to HIV risk, but there is limited understanding of how it relates to mental health among HIV-infected women. Methods: Participants were 270 HIV-infected women from the Uganda AIDS Rural Treatment Outcomes study, a prospective cohort of individuals initiating antiretroviral therapy (ART) in Mbarara, Uganda. Our primary predictor was baseline sexual relationship power as measured by the Sexual Relationship Power Scale (SRPS). The primary outcome was depression severity, measured with the Hopkins Symptom Checklist (HSCL), and a secondary outcome was a functional scale for mental health status (MHS). Adjusted models controlled for socio-demographic factors, CD4 count, alcohol and tobacco use, baseline WHO stage 4 disease, social support, and duration of ART. Results: The mean HSCL score was 1.34 and 23.7% of participants had HSCL scores consistent with probable depression (HSCL > 1.75). Compared to participants with low SRPS scores, individuals with both moderate (coefficient b = -0.21; 95% CI, -0.36 to -0.07) and high power (b = -0.21; 95% CI, -0.36 to -0.06) reported decreased depressive symptomology. High SRPS scores halved the likelihood of women meeting criteria for probable depression (adjusted odds ratio = 0.44; 95% CI, 0.20 to 0.93). In lagged models, low SRPS predicted subsequent depression severity, but depression did not predict subsequent changes in SPRS. Results were similar for MHS, with lagged models showing SRPS predicts subsequent mental health, but not visa versa. Both Decision-Making Dominance and Relationship Control subscales of SRPS were associated with depression symptom severity. Conclusions: HIV-infected women with high sexual relationship power had lower depression and higher mental health status than women with low power. Interventions to improve equity in decision-making and control within dyadic partnerships are critical to prevent HIV transmission and to optimize mental health of HIV-infected women. C1 [Hatcher, Abigail M.; Hunt, Peter W.; Weiser, Sheri D.] Univ Calif San Francisco, Div HIV AIDS, Dept Med, San Francisco, CA 94143 USA. [Hatcher, Abigail M.] Univ Witwatersrand, Wits Reprod Hlth & HIV Inst, Johannesburg, South Africa. [Tsai, Alexander C.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Tsai, Alexander C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Tsai, Alexander C.; Bangsberg, David R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Kumbakumba, Elias; Bangsberg, David R.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Dworkin, Shari L.] Univ Calif San Francisco, Dept Social & Behav Sci, San Francisco, CA USA. [Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Clark, Gina] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Hatcher, AM (reprint author), Univ Calif San Francisco, Div HIV AIDS, Dept Med, San Francisco, CA 94143 USA. EM hatchera@globalhealth.ucsf.edu RI Hatcher, Abigail/G-9128-2011; OI Hatcher, Abigail/0000-0002-4150-1405; Tsai, Alexander/0000-0001-6397-7917 FU NIH [K23 MH-079713, MH-79713-03S1, R01 MH-54907, P30 AI27763, K24 MH-87227, K23 MH-096620]; Tim and Jane Meyer Family Foundation; Burke Family Foundation; Paiko Foundation FX The study was funded by NIH K23 MH-079713, MH-79713-03S1, NIH R01 MH-54907, NIH P30 AI27763, and the Tim and Jane Meyer Family Foundation. The authors acknowledge the following additional sources of salary support: the Burke Family Foundation, NIH K24 MH-87227, K23 MH-096620, and the Paiko Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 89 TC 10 Z9 11 U1 5 U2 30 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 26 PY 2012 VL 7 IS 12 AR e49821 DI 10.1371/journal.pone.0049821 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 071TV UT WOS:000313618800004 PM 23300519 ER PT J AU Jiao, S Hsu, L Berndt, S Bezieau, S Brenner, H Buchanan, D Caan, BJ Campbell, PT Carlson, CS Casey, G Chan, AT Chang-Claude, J Chanock, S Conti, DV Curtis, KR Duggan, D Gallinger, S Gruber, SB Harrison, TA Hayes, RB Henderson, BE Hoffmeister, M Hopper, JL Hudson, TJ Hutter, CM Jackson, RD Jenkins, MA Kantor, ED Kolonel, LN Kury, S Le Marchand, L Lemire, M Newcomb, PA Potter, JD Qu, CH Rosse, SA Schoen, RE Schumacher, FR Seminara, D Slattery, ML Ulrich, CM Zanke, BW Peters, U AF Jiao, Shuo Hsu, Li Berndt, Sonja Bezieau, Stephane Brenner, Hermann Buchanan, Daniel Caan, Bette J. Campbell, Peter T. Carlson, Christopher S. Casey, Graham Chan, Andrew T. Chang-Claude, Jenny Chanock, Stephen Conti, David V. Curtis, Keith R. Duggan, David Gallinger, Steven Gruber, Stephen B. Harrison, Tabitha A. Hayes, Richard B. Henderson, Brian E. Hoffmeister, Michael Hopper, John L. Hudson, Thomas J. Hutter, Carolyn M. Jackson, Rebecca D. Jenkins, Mark A. Kantor, Elizabeth D. Kolonel, Laurence N. Kuery, Sebastien Le Marchand, Loic Lemire, Mathieu Newcomb, Polly A. Potter, John D. Qu, Conghui Rosse, Stephanie A. Schoen, Robert E. Schumacher, Fred R. Seminara, Daniela Slattery, Martha L. Ulrich, Cornelia M. Zanke, Brent W. Peters, Ulrike TI Genome-Wide Search for Gene-Gene Interactions in Colorectal Cancer SO PLOS ONE LA English DT Article ID SUSCEPTIBILITY LOCI; ASSOCIATION SCAN; ENVIRONMENT INTERACTIONS; RANDOM FORESTS; HUMAN-DISEASES; VARIANTS; RISK; METAANALYSIS; EPISTASIS; SEROTONIN AB Genome-wide association studies (GWAS) have successfully identified a number of single-nucleotide polymorphisms (SNPs) associated with colorectal cancer (CRC) risk. However, these susceptibility loci known today explain only a small fraction of the genetic risk. Gene-gene interaction (GxG) is considered to be one source of the missing heritability. To address this, we performed a genome-wide search for pair-wise GxG associated with CRC risk using 8,380 cases and 10,558 controls in the discovery phase and 2,527 cases and 2,658 controls in the replication phase. We developed a simple, but powerful method for testing interaction, which we term the Average Risk Due to Interaction (ARDI). With this method, we conducted a genome-wide search to identify SNPs showing evidence for GxG with previously identified CRC susceptibility loci from 14 independent regions. We also conducted a genome-wide search for GxG using the marginal association screening and examining interaction among SNPs that pass the screening threshold (p < 10(-4)). For the known locus rs10795668 (10p14), we found an interacting SNP rs367615 (5q21) with replication p = 0.01 and combined p = 4.19x10(-8). Among the top marginal SNPs after LD pruning (n = 163), we identified an interaction between rs1571218 (20p12.3) and rs10879357 (12q21.1) (nominal combined p = 2.51x10(-6); Bonferroni adjusted p = 0.03). Our study represents the first comprehensive search for GxG in CRC, and our results may provide new insight into the genetic etiology of CRC. C1 [Jiao, Shuo; Hsu, Li; Carlson, Christopher S.; Curtis, Keith R.; Harrison, Tabitha A.; Hutter, Carolyn M.; Kantor, Elizabeth D.; Newcomb, Polly A.; Potter, John D.; Qu, Conghui; Rosse, Stephanie A.; Ulrich, Cornelia M.; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Berndt, Sonja; Chanock, Stephen] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Bezieau, Stephane; Kuery, Sebastien] CHU Nantes, Serv Genet Med, F-44035 Nantes 01, France. [Bezieau, Stephane; Hoffmeister, Michael] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Buchanan, Daniel] Queensland Inst Med Res, Canc & Populat Studies Grp, Brisbane, Qld 4006, Australia. [Caan, Bette J.] Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94611 USA. [Campbell, Peter T.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Carlson, Christopher S.; Newcomb, Polly A.; Potter, John D.; Ulrich, Cornelia M.; Peters, Ulrike] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Casey, Graham; Conti, David V.; Gruber, Stephen B.; Henderson, Brian E.; Schumacher, Fred R.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [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. [Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Duggan, David] Translat Genom Res Inst, Phoenix, AZ USA. [Gallinger, Steven] Toronto Gen Hosp, Univ Hlth Network, Dept Surg, Toronto, ON, Canada. [Hayes, Richard B.] NYU, Sch Med, Div Epidemiol, New York, NY USA. [Hopper, John L.; Jenkins, Mark A.] Univ Melbourne, Melbourne Sch Populat Hlth, Melbourne, Vic, Australia. [Hudson, Thomas J.; Lemire, Mathieu] Ontario Inst Canc Res, Toronto, ON, Canada. [Hudson, Thomas J.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. [Hudson, Thomas J.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Jackson, Rebecca D.] Ohio State Univ, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA. [Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA. [Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand. [Schoen, Robert E.] Univ Pittsburgh, Med Ctr, Dept Med & Epidemiol, Pittsburgh, PA USA. [Seminara, Daniela] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Slattery, Martha L.] Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT USA. [Ulrich, Cornelia M.] Natl Ctr Tumor Dis, Div Prevent Oncol, Heidelberg, Germany. [Zanke, Brent W.] Ottawa Hosp, Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada. RP Jiao, S (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA. EM sjiao@fhcrc.org RI Gallinger, Steven/E-4575-2013; Hoffmeister, Michael/B-5745-2012; KURY, Sebastien/G-5971-2015; Bezieau, stephane/G-5621-2015; Jenkins, Mark/P-7803-2015; Brenner, Hermann/B-4627-2017; OI Hoffmeister, Michael/0000-0002-8307-3197; KURY, Sebastien/0000-0001-5497-0465; Bezieau, stephane/0000-0003-0095-1319; Buchanan, Daniel/0000-0003-2225-6675; Jenkins, Mark/0000-0002-8964-6160; Brenner, Hermann/0000-0002-6129-1572; Kantor, Elizabeth/0000-0002-9124-5323; Potter, John/0000-0001-5439-1500 FU Hospital Clinical Research Program (PHRC); Regional Council of Pays de la Loire; Groupement des Entreprises Francaises dans la Lutte contre le Cancer (GEFLUC); Association Anne de Bretagne Genetique; Ligue Regionale Contre le Cancer (LRCC); National Cancer Institute, National Institutes of Health [U01 CA074783, U01 CA122839]; Ontario Research Fund [GL2]; Canadian Institutes of Health Research; Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society Research Institute; Ontario Institute for Cancer Research; National Cancer Institute [R01 CA60987]; National Cancer Institute, National Institutes of Health under RFA [CA-95-011]; Australasian Colorectal Cancer Family Registry [U01 CA097735]; Seattle Colorectal Cancer Family Registry [U01 CA074794]; Ontario Registry for Studies of Familial Colorectal Cancer [U01 CA074783]; German Research Council (Deutsche Forschungsgemeinschaft) [BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1]; German Federal Ministry of Education and Research [01KH0404, 01ER0814]; National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services [R01 CA48998, U01 CA137088, R01 CA059045]; National Institutes of Health [P01 CA 055075, R01 137178, P50 CA 127003, P01 CA 087969, CA42182, R01 CA076366]; Intramural Research Program of the Division of Cancer Epidemiology and Genetics; Division of Cancer Prevention, National Cancer Institute, NIH, DHHS; Intramural Research Program of the National Cancer Institute; National Institutes of Health, Genes, Environment and Health Initiative [NIH GEI] [Z01 CP 010200]; National Cancer Institute; Gene Environment Association Studies, GENEVA Coordinating Center [U01 HG004446]; NIH GEI [U01 HG 004438]; National Institutes of Health from the National Cancer Institute and Office of Dietary Supplements [K05 CA154337]; National Heart, Lung, and Blood Institute, National Institutes of Health, U. S. Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221, 268200764316C]; [R37 CA54281]; [P01 CA033619]; [R01 CA63464] FX ASTERISK was funded by a Hospital Clinical Research Program (PHRC) and supported by the Regional Council of Pays de la Loire, the Groupement des Entreprises Francaises dans la Lutte contre le Cancer (GEFLUC), the Association Anne de Bretagne Genetique and the Ligue Regionale Contre le Cancer (LRCC). ARCTIC is partly supported by the National Cancer Institute, National Institutes of Health through funding allocated to the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783); see CCFR section below. ARCTIC is also supported by a GL2 grant from the Ontario Research Fund, the Canadian Institutes of Health Research, and the Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society Research Institute. TJH and BWZ are recipients of Senior Investigator Awards from the Ontario Institute for Cancer Research, through generous support from the Ontario Ministry of Economic Development and Innovation. COLO2&3 is supported by the National Cancer Institute (R01 CA60987). CCFR is supported by the National Cancer Institute, National Institutes of Health under RFA # CA-95-011 and through cooperative agreements with members of the Colon Cancer Family Registry and P.I.s. This genome wide scan was supported by the National Cancer Institute, National Institutes of Health by U01 CA122839. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the CFRs, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government or the CFR. The following Colon CFR centers contributed data to this manuscript and were supported by the following sources: Australasian Colorectal Cancer Family Registry (U01 CA097735), Seattle Colorectal Cancer Family Registry (U01 CA074794) and Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783). DACHS was supported by grants from the German Research Council (Deutsche Forschungsgemeinschaft, BR 1704/6-1, BR 1704/6-3, BR 1704/6-4 and CH 117/1-1), and the German Federal Ministry of Education and Research (01KH0404 and 01ER0814). DALS was supported by the National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services (R01 CA48998 to MLS). GECCO is supported by National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services (U01 CA137088). Funding for the genome-wide scan of DALS, PLCO, and WHI was provided by the National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services (R01 CA059045). HPFS, NHS, PHS: The National Institutes of Health supported HPFS (P01 CA 055075, R01 137178, P50 CA 127003), NHS (R01 137178, P50 CA 127003, P01 CA 087969), and PHS (CA42182). MEC is supported by R37 CA54281, P01 CA033619, and R01 CA63464. 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, National Cancer Institute, NIH, DHHS. Control samples were genotyped as part of the Cancer Genetic Markers of Susceptibility (CGEMS) prostate cancer scan, supported by the Intramural Research Program of the National Cancer Institute. The datasets used in this analysis were accessed with appropriate approval through the dbGaP online resource (http://www.cgems.cancer.gov/data_acess.html) through dbGaP accession number 000207v.1p1.c1.; (National Cancer Institute (2009) Cancer Genetic Markers of Susceptibility (CGEMS) data website, http://cgems.cancer.gov/data_access.html; Yeager et al. 2007). Control samples were also genotyped as part of the GWAS of Lung Cancer and Smoking (Landi et al. 2009). Funding for this work was provided through the National Institutes of Health, Genes, Environment and Health Initiative [NIH GEI] (Z01 CP 010200). The human subjects participating in the GWAS are derived from the Prostate, Lung, Colon and Ovarian Screening Trial and the study is supported by intramural resources of the National Cancer Institute. Assistance with genotype cleaning, as well as with general study coordination, was provided by the Gene Environment Association Studies, GENEVA Coordinating Center (U01 HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the NIH GEI (U01 HG 004438). The datasets used for the analyses described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/gap through dbGaP accession number phs000093. PMH was supported by the National Institutes of Health (R01 CA076366 to PAN). VITAL was supported, in part, by the National Institutes of Health (K05 CA154337) from the National Cancer Institute and Office of Dietary Supplements. WHI: The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221, and 268200764316C. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 64 TC 21 Z9 22 U1 0 U2 17 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 26 PY 2012 VL 7 IS 12 AR e52535 DI 10.1371/journal.pone.0052535 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 071TV UT WOS:000313618800103 PM 23300701 ER PT J AU Song, GJ Koksal, AC Lu, CF Springer, TA AF Song, Gaojie Koksal, Adem C. Lu, Chafen Springer, Timothy A. TI Shape change in the receptor for gliding motility in Plasmodium sporozoites SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID A-DOMAIN; APICOMPLEXAN PARASITES; TOXOPLASMA-GONDII; SURFACE PROTEIN-2; MALARIA VACCINES; MAMMALIAN-CELLS; FALCIPARUM TRAP; LAYERED FOLD; I-DOMAIN; INTEGRIN AB Sporozoite gliding motility and invasion of mosquito and vertebrate host cells in malaria is mediated by thrombospondin repeat anonymous protein (TRAP). Tandem von Willebrand factor A (VWA) and thrombospondin type I repeat (TSR) domains in TRAP connect through proline-rich stalk, transmembrane, and cytoplasmic domains to the parasite actin-dependent motility apparatus. We crystallized fragments containing the VWA and TSR domains from Plasmodium vivax and Plasmodium falciparum in different crystal lattices. TRAP VWA domains adopt closed and open conformations, and bind a Mg2+ ion at a metal ion-dependent adhesion site implicated in ligand binding. Metal ion coordination in the open state is identical to that seen in the open high-affinity state of integrin I domains. The closed VWA conformation associates with a disordered TSR domain. In contrast, the open VWA conformation crystallizes with an extensible beta ribbon and ordered TSR domain. The extensible beta ribbon is composed of disulfide-bonded segments N- and C-terminal to the VWA domain that are largely drawn out of the closed VWA domain in a 15 angstrom movement to the open conformation. The extensible beta ribbon and TSR domain overlap at a conserved interface. The VWA, extensible beta ribbon, and TSR domains adopt a highly elongated overall orientation that would be stabilized by tensile force exerted across a ligand-receptor complex by the actin motility apparatus of the sporozoite. Our results provide insights into regulation of "stick-and-slip" parasite motility and for development of sporozoite subunit vaccines. C1 [Springer, Timothy A.] Childrens Hosp, Immune Dis Inst, Program Cellular & Mol Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Childrens Hosp, Immune Dis Inst, Program Cellular & Mol Med, 300 Longwood Ave, Boston, MA 02115 USA. EM springer@idi.harvard.edu OI Koksal, Adem/0000-0002-3163-7421 FU National Institutes of Health [AI095686] FX We thank Jianghai Zhu for help with structure solution and model building. We thank the staff at the General Medical Sciences and Cancer Institutes Structural Biology Facility (GM/CA) beamline 23-ID at Advanced Photon Source (Argonne, IL) for data collection support. This work was supported by National Institutes of Health Grant AI095686. NR 48 TC 20 Z9 20 U1 1 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 26 PY 2012 VL 109 IS 52 BP 21420 EP 21425 DI 10.1073/pnas.1218581109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 071WR UT WOS:000313627700061 PM 23236185 ER PT J AU Kastrup, CJ Nahrendorf, M Figueiredo, JL Lee, H Kambhampati, S Lee, T Cho, SW Gorbatov, R Iwamoto, Y Dang, TT Dutta, P Yeon, JH Cheng, H Pritchard, CD Vegas, AJ Siegel, CD MacDougall, S Okonkwo, M Thai, A Stone, JR Coury, AJ Weissleder, R Langer, R Anderson, DG AF Kastrup, Christian J. Nahrendorf, Matthias Figueiredo, Jose Luiz Lee, Haeshin Kambhampati, Swetha Lee, Timothy Cho, Seung-Woo Gorbatov, Rostic Iwamoto, Yoshiko Dang, Tram T. Dutta, Partha Yeon, Ju Hun Cheng, Hao Pritchard, Christopher D. Vegas, Arturo J. Siegel, Cory D. MacDougall, Samantha Okonkwo, Michael Anh Thai Stone, James R. Coury, Arthur J. Weissleder, Ralph Langer, Robert Anderson, Daniel G. TI Painting blood vessels and atherosclerotic plaques with an adhesive drug depot SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE biomaterials; catechol; delivery; endoluminal paving ID CORONARY ATHEROSCLEROSIS; CARDIOVASCULAR-DISEASE; VULNERABLE PLAQUE; HYDROGEL BARRIERS; STENT THROMBOSIS; ALGINATE; MECHANISMS; DELIVERY; PERSPECTIVES; DEGRADATION AB The treatment of diseased vasculature remains challenging, in part because of the difficulty in implanting drug-eluting devices without subjecting vessels to damaging mechanical forces. Implanting materials using adhesive forces could overcome this challenge, but materials have previously not been shown to durably adhere to intact endothelium under blood flow. Marine mussels secrete strong underwater adhesives that have been mimicked in synthetic systems. Here we develop a drug-eluting bioadhesive gel that can be locally and durably glued onto the inside surface of blood vessels. In a mouse model of atherosclerosis, inflamed plaques treated with steroid-eluting adhesive gels had reduced macrophage content and developed protective fibrous caps covering the plaque core. Treatment also lowered plasma cytokine levels and biomarkers of inflammation in the plaque. The drug-eluting devices developed here provide a general strategy for implanting therapeutics in the vasculature using adhesive forces and could potentially be used to stabilize rupture-prone plaques. C1 [Kastrup, Christian J.; Kambhampati, Swetha; Lee, Timothy; Dang, Tram T.; Cheng, Hao; Pritchard, Christopher D.; Vegas, Arturo J.; MacDougall, Samantha; Okonkwo, Michael; Anh Thai; Langer, Robert; Anderson, Daniel G.] MIT, David H Koch Inst Integrated Canc Res, Cambridge, MA 02139 USA. [Langer, Robert; Anderson, Daniel G.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Langer, Robert; Anderson, Daniel G.] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Kastrup, Christian J.; Yeon, Ju Hun] Univ British Columbia, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada. [Kastrup, Christian J.; Yeon, Ju Hun] Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z4, Canada. [Nahrendorf, Matthias; Figueiredo, Jose Luiz; Gorbatov, Rostic; Iwamoto, Yoshiko; Dutta, Partha; Siegel, Cory D.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Stone, James R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Stone, James R.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Lee, Haeshin] Korea Adv Inst Sci & Technol, Dept Chem, Grad Sch Nanosci & Technol, Taejon 305701, South Korea. [Cho, Seung-Woo] Yonsei Univ, Dept Biotechnol, Seoul 120749, South Korea. [Cheng, Hao] Drexel Univ, Dept Mat Sci & Engn, Philadelphia, PA 19104 USA. [Coury, Arthur J.] Coury Consulting Serv, Boston, MA 02116 USA. RP Langer, R (reprint author), MIT, David H Koch Inst Integrated Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM rlanger@mit.edu; dgander@mit.edu RI Lee, Haeshin/C-1720-2011; Dang, Tram/E-7966-2011 OI Lee, Haeshin/0000-0003-3961-9727; FU National Institutes of Health [DE016516, R01HL096576, U24-CA92782]; Medtronic, Inc.; Canadian Institutes of Health Research [MOP119426]; Pioneer Research Program [R31-10071, WCU-2z011-0001696]; Juvenile Diabetes Research Foundation FX We thank E. Aikawa, J. Donners, E. Edelman, A. Jaklenec, S. Lyu, S. Lyle, A. Nathan, S. Oesterle, R. Sparer, P. Wojciechowski, and H. Yin for helpful suggestions; and Z. Mueller and J. Sullivan for help with in vivo imaging. C. K. is a Johnson & Johnson Fellow of the Life Sciences Research Foundation. This work was funded by National Institutes of Health Grants DE016516 (to D. G. A. and R. L.), R01HL096576 (to M.N.), and U24-CA92782 (to R. W.); Medtronic, Inc.; Canadian Institutes of Health Research Grant MOP119426; the Pioneer Research Program Grants R31-10071 and WCU-2z011-0001696 (to H. L.); and the Juvenile Diabetes Research Foundation (D. G. A. and R. L.). This work was carried out in part through the use of Massachusetts Institute of Technology's Microsystems Technology Laboratories, Swanson Biotechnology Center, and the Mouse Imaging Program in the Center for Systems Biology at Massachusetts General Hospital. NR 34 TC 43 Z9 43 U1 4 U2 115 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 26 PY 2012 VL 109 IS 52 BP 21444 EP 21449 DI 10.1073/pnas.1217972110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 071WR UT WOS:000313627700065 PM 23236189 ER PT J AU Grad, YH Lipsitch, M Griggs, AD Haas, BJ Shea, TP McCowan, C Montmayeur, A FitzGerald, M Wortman, JR Krogfelt, KA Bingen, E Weill, FX Tietze, E Flieger, A Lander, ES Nusbaum, C Birren, BW Hung, DT Hanage, WP AF Grad, Yonatan H. Lipsitch, Marc Griggs, Allison D. Haas, Brian J. Shea, Terrance P. McCowan, Caryn Montmayeur, Anna FitzGerald, Michael Wortman, Jennifer R. Krogfelt, Karen A. Bingen, Edouard Weill, Francois-Xavier Tietze, Erhard Flieger, Antje Lander, Eric S. Nusbaum, Chad Birren, Bruce W. Hung, Deborah T. Hanage, William P. TI Reply to Guy et al.: Support for a bottleneck in the 2011 Escherichia coli O104:H4 outbreak in Germany SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Letter C1 [Grad, Yonatan H.; Hung, Deborah T.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Grad, Yonatan H.; Lipsitch, Marc; Hanage, William P.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Ctr Communicable Dis Dynam, Boston, MA 02115 USA. [Lipsitch, Marc] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Griggs, Allison D.; Haas, Brian J.; Shea, Terrance P.; McCowan, Caryn; Montmayeur, Anna; FitzGerald, Michael; Wortman, Jennifer R.; Lander, Eric S.; Nusbaum, Chad; Birren, Bruce W.; Hung, Deborah T.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02142 USA. [Krogfelt, Karen A.] Statens Serum Inst, Dept Microbial Surveillance & Res, DK-2300 Copenhagen, Denmark. [Bingen, Edouard] Hop Robert Debre, AP HP, Microbiol Serv, Lab Ctr Natl Reference Escherichia Coli & Shigell, F-75019 Paris, France. [Bingen, Edouard] Univ Paris Diderot, F-75505 Paris, France. [Weill, Francois-Xavier] Ctr Natl Reference Escherichia Coli & Shigella, Unite Bacteries Pathogenes Enter, Inst Pasteur, F-75015 Paris, France. [Tietze, Erhard; Flieger, Antje] Robert Koch Inst, Div Bacterial Infect, D-38855 Wernigerode, Germany. [Tietze, Erhard; Flieger, Antje] Robert Koch Inst, Natl Reference Ctr Salmonella & Other Enter Bacte, D-38855 Wernigerode, Germany. [Lander, Eric S.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Lander, Eric S.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Hung, Deborah T.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Hung, Deborah T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Lander, ES (reprint author), Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02142 USA. EM lander@broadinstitute.org RI Krogfelt , Karen Angeliki/O-8145-2016; OI Krogfelt , Karen Angeliki/0000-0001-7536-3453; Wortman, Jennifer/0000-0002-8713-1227; Montmayeur, Anna/0000-0002-8132-1716; Weill, Francois-Xavier/0000-0001-9941-5799; Lipsitch, Marc/0000-0003-1504-9213 FU NIAID NIH HHS [T32 AI007061] NR 4 TC 1 Z9 1 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 26 PY 2012 VL 109 IS 52 BP E3629 EP E3630 DI 10.1073/pnas.1209419110 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 071WR UT WOS:000313627700006 PM 23479789 ER PT J AU Hadj-Bouziane, F Liu, N Bell, AH Gothard, KM Luh, WM Tootell, RBH Murray, EA Ungerleider, LG AF Hadj-Bouziane, Fadila Liu, Ning Bell, Andrew H. Gothard, Katalin M. Luh, Wen-Ming Tootell, Roger B. H. Murray, Elisabeth A. Ungerleider, Leslie G. TI Amygdala lesions disrupt modulation of functional MRI activity evoked by facial expression in the monkey inferior temporal cortex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE neuroimaging; nonhuman primate; social stimuli; temporal lobe ID PREFRONTAL CORTEX; RHESUS-MONKEYS; NEUROTOXIC LESIONS; MACAQUE MONKEY; HIPPOCAMPAL-FORMATION; IMPAIRED RECOGNITION; ORBITOFRONTAL CORTEX; SELECTIVE RESPONSES; EMOTIONAL RESPONSES; NONHUMAN-PRIMATES AB We previously showed that facial expressions modulate functional MRI activity in the face-processing regions of the macaque monkey's amygdala and inferior temporal (IT) cortex. Specifically, we showed that faces expressing emotion yield greater activation than neutral faces; we term this difference the "valence effect." We hypothesized that amygdala lesions would disrupt the valence effect by eliminating the modulatory feedback from the amygdala to the IT cortex. We compared the valence effects within the IT cortex in monkeys with excitotoxic amygdala lesions (n = 3) with those in intact control animals (n = 3) using contrast agent-based functional MRI at 3 T. Images of four distinct monkey facial expressions-neutral, aggressive (open mouth threat), fearful (fear grin), and appeasing (lip smack)-were presented to the subjects in a blocked design. Our results showed that in monkeys with amygdala lesions the valence effects were strongly disrupted within the IT cortex, whereas face responsivity (neutral faces > scrambled faces) and face selectivity (neutral faces > non-face objects) were unaffected. Furthermore, sparing of the anterior amygdala led to intact valence effects in the anterior IT cortex (which included the anterior face-selective regions), whereas sparing of the posterior amygdala led to intact valence effects in the posterior IT cortex (which included the posterior face-selective regions). Overall, our data demonstrate that the feedback projections from the amygdala to the IT cortex mediate the valence effect found there. Moreover, these modulatory effects are consistent with an anterior-to-posterior gradient of projections, as suggested by classical tracer studies. C1 [Hadj-Bouziane, Fadila; Liu, Ning; Bell, Andrew H.; Tootell, Roger B. H.; Ungerleider, Leslie G.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Murray, Elisabeth A.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. [Luh, Wen-Ming] NIMH, Funct MRI Facil, NIH, Bethesda, MD 20892 USA. [Gothard, Katalin M.] Univ Arizona, Coll Med, Dept Physiol, Tucson, AZ 85724 USA. [Tootell, Roger B. H.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Hadj-Bouziane, F (reprint author), CNRS, INSERM, U1028, Lyon Neurosci Res Ctr,ImpAct Team,UMR 5292, F-69500 Bron, France. EM fadila.hadj-bouziane@inserm.fr; ungerlel@mail.nih.gov OI Bell, Andrew/0000-0001-8420-4622; Murray, Elisabeth/0000-0003-1450-1642 FU National Institute of Mental Health Intramural Research Program FX We thank Shruti Japee, Ziad Saad, and Gang Chen for help with data analysis; Lucas Glover, Fern Baldwin, and James Ellis for assistance with animal training and scanning; Gary Griffiths for providing the contrast agent, MION; George Dold, David Ide, and Tom Talbot for technical assistance; and Kadharbatcha Saleem for preparing images of Nissl-stained histological sections. This study was supported by the National Institute of Mental Health Intramural Research Program (F.H.-B., N.L., A.H.B., E.A.M., and L.G.U.). NR 68 TC 32 Z9 32 U1 1 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 26 PY 2012 VL 109 IS 52 BP E3640 EP E3648 DI 10.1073/pnas.1218406109 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 071WR UT WOS:000313627700008 PM 23184972 ER PT J AU Budin, I Debnath, A Szostak, JW AF Budin, Itay Debnath, Anik Szostak, Jack W. TI Concentration-Driven Growth of Model Protocell Membranes SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID FATTY-ACID VESICLES; LAURDAN FLUORESCENCE; MICELLES; POLARIZATION; AMPHIPHILES; RELAXATION; DIVISION AB The first protocell membranes may have assembled from fatty acids and related single-chain lipids available in the prebiotic environment. Prior to the evolution of complex cellular machinery, spontaneous protocell membrane growth and division had to result from the intrinsic physicochemical properties of these molecules, in the context of specific environmental conditions. Depending on the nature of the chemical and physical environment, fatty acids can partition between several different phases, including soluble monomers, micelles, and lamellar vesicles. Here we address the concentration dependence of fatty acid aggregation, which is dominated by entropic considerations. We quantitatively distinguish between fatty acid phases using a combination of physical and spectroscopic techniques, including the use of the fluorescent fatty acid analogue Laurdan, whose emission spectrum is sensitive to structural differences between micellar and lamellar aggregates. We find that the monomer aggregate transition largely follows a characteristic pseudophase model of molecular aggregation but that the composition of the aggregate phase is also concentration dependent. At low amphiphile concentrations above the critical aggregate concentration, vesicles coexist with a significant proportion of micelles, while more concentrated solutions favor the lamellar vesicle phase. We subsequently show that the micelle vesicle equilibrium can be used to drive the growth of pre-existing vesicles upon an increase in amphiphile concentration either through solvent evaporation or following the addition of excess lipids. We propose a simple model for a primitive environmentally driven cell cycle, in which protocell membrane growth results from evaporative concentration, followed by shear force or photochemically induced division. C1 [Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, 185 Cambridge St, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu FU NASA [EXB02-0031-0018]; Harvard University; Harvard Origins of Life Initiative FX J.W.S. is an investigator of the Howard Hughes Medical Institute. This research was supported in part by grant EXB02-0031-0018 from the NASA Exobiology Program to J.W.S. I.B. was supported by a fellowship from Harvard University. A.D. was supported by a fellowship from the Harvard Origins of Life Initiative. The authors thank Noam Prywes, Raphael Bruckner, Christian Hentrich, Craig Blain, and Anders Bjorkbom for helpful discussions and comments on the manuscript. NR 31 TC 27 Z9 28 U1 5 U2 92 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD DEC 26 PY 2012 VL 134 IS 51 BP 20812 EP 20819 DI 10.1021/ja310382d PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 065NC UT WOS:000313154200038 PM 23198690 ER PT J AU Mulla, SM Scott, IA Jackevicius, CA You, JJ Guyatt, GH AF Mulla, Sohail M. Scott, Ian A. Jackevicius, Cynthia A. You, John J. Guyatt, Gordon H. TI How to Use a Noninferiority Trial Users' Guides to the Medical Literature SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID NONVALVULAR ATRIAL-FIBRILLATION; EQUIVALENCE RANDOMIZED-TRIALS; NON-INFERIORITY; GOOD ENOUGH; OPEN-LABEL; RIVAROXABAN; WARFARIN AB Clinical investigators are increasingly testing treatments that have the primary benefit of decreased burden or harms relative to an existing standard. The goal of the resulting randomized trials-called noninferiority trials-is to establish that the novel treatment's effectiveness is not substantially less than the existing standard. Conclusions from these trials are, however, based on noninferiority thresholds specified by authors whose judgments may not coincide with those of patients and clinicians. This article highlights issues related to validity, interpretation, and applicability of results specific to noninferiority trials. Suboptimal administration of standard treatment or exclusive reliance on the analyze-as-randomized approach that is standard for conventional superiority trials may produce misleading results in noninferiority trials. Clinicians should judge whether the novel treatment's impact on effectiveness outcomes-the prime reason for wanting to prescribe it-is sufficiently close to that of standard treatment that they are comfortable substituting it for the existing standard. Trading off desirable and undesirable consequences is an individual decision: given the benefits of a novel treatment, some patients may perceive the uncertainty regarding a reduction in treatment effectiveness as acceptable while others may not. JAMA 2012;308(24):2605-2611 C1 [Mulla, Sohail M.; You, John J.; Guyatt, Gordon H.] McMaster Univ, Fac Hlth Sci, Dept Clin Epidemiol & Biostat, Hamilton, ON L8N 3Z5, Canada. [You, John J.; Guyatt, Gordon H.] McMaster Univ, Fac Hlth Sci, Dept Med, Hamilton, ON L8N 3Z5, Canada. [Scott, Ian A.] Princess Alexandra Hosp, Dept Internal Med & Clin Epidemiol, Brisbane, Qld 4102, Australia. [Jackevicius, Cynthia A.; You, John J.] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Western Univ Hlth Sci, Coll Pharm, Dept Pharm Practice & Adm, Pomona, CA USA. [Jackevicius, Cynthia A.] Univ Toronto, Fac Med, Inst Hlth Policy Management & Evaluat, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Univ Hlth Network, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Guyatt, GH (reprint author), McMaster Univ, Fac Hlth Sci, Dept Clin Epidemiol & Biostat, 1200 Main St W,Room 2C12, Hamilton, ON L8N 3Z5, Canada. EM guyatt@mcmaster.ca RI Scott, Ian/F-1482-2011 NR 21 TC 25 Z9 26 U1 0 U2 22 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 26 PY 2012 VL 308 IS 24 BP 2605 EP 2611 DI 10.1001/2012.jama.11235 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 062JR UT WOS:000312916600026 PM 23268519 ER PT J AU Pitman, MB AF Pitman, Martha Bishop TI Revised international consensus guidelines for the management of patients with mucinous cysts SO CANCER CYTOPATHOLOGY LA English DT Editorial Material ID INCIDENTAL PANCREATIC CYSTS; FLUID ANALYSIS; CLINICOPATHOLOGICAL CHARACTERISTICS; SYMPTOMATIC PATIENTS; RISK-ASSESSMENT; ADDS VALUE; NEOPLASMS; MALIGNANCY; DIAGNOSIS; CYTOLOGY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Pitman, MB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM mpitman@partners.org NR 34 TC 9 Z9 9 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD DEC 25 PY 2012 VL 120 IS 6 BP 361 EP 365 DI 10.1002/cncy.21235 PG 5 WC Oncology; Pathology SC Oncology; Pathology GA 057AR UT WOS:000312534500002 PM 23042725 ER PT J AU Rogers, JH Goldstein, I Kandzari, DE Kohler, TS Stinis, CT Wagner, PJ Popma, JJ Jaff, MR Rocha-Singh, KJ AF Rogers, Jason H. Goldstein, Irwin Kandzari, David E. Koehler, Tobias S. Stinis, Curtiss T. Wagner, Paula J. Popma, Jeffrey J. Jaff, Michael R. Rocha-Singh, Krishna J. TI Zotarolimus-Eluting Peripheral Stents for the Treatment of Erectile Dysfunction in Subjects With Suboptimal Response to Phosphodiesterase-5 Inhibitors SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE atherosclerosis; erectile dysfunction diagnosis; first-in-man; internal pudendal artery; zotarolimus-eluting stent ID TRANS-LUMINAL ANGIOPLASTY; ARTERIOGENIC IMPOTENCE; INTERNATIONAL INDEX; PUDENDAL ARTERY; VASCULOGENIC IMPOTENCE; CARDIOVASCULAR-DISEASE; STEAL SYNDROME; RISK-FACTORS; ATHEROSCLEROSIS; METAANALYSIS AB Objectives This study sought to evaluate the safety and feasibility of zotarolimus-eluting stent implantation in focal atherosclerotic lesions of the internal pudendal arteries among men with erectile dysfunction (ED) and a suboptimal response to phosphodiesterase-5 inhibitors. Background ED, a common condition, is often mediated by atherosclerosis. Current treatment options are limited. Methods Male subjects with atherosclerotic ED and a suboptimal response to phosphodiesterase-5 inhibitors were enrolled in this prospective, multicenter, single-armed safety and feasibility trial. A novel combination of clinical, duplex ultrasound, and invasive angiographic factors were used to determine eligibility for stent therapy. The primary safety endpoint was any major adverse event 30 days after the procedure. The primary feasibility end point was improvement in the International Index of Erectile Function (Erectile Dysfunction Domain) score >= 4 points in >= 50% of subjects at 3 months. We report 6-month follow-up results, including duplex ultrasound and angiography. Results Forty-five lesions were treated with stents in 30 subjects. Procedural success was 100% with no major adverse events through follow-up. The primary feasibility endpoint at 6 months was achieved by 59.3% of intention-to-treat subjects (95% confidence interval: 38.8% to 77.6%) and 69.6% of per-protocol subjects (95% confidence interval: 47.1% to 86.8%). Duplex ultrasound peak systolic velocity of the cavernosal arteries increased from baseline by 14.4 +/- 10.7 cm/s at 30 days and 22.5 +/- 23.7 cm/s at 6 months. Angiographic binary restenosis (>= 50% lumen diameter stenosis) was reported in 11 (34.4%) of 32 lesions. Conclusions Among patients with ED and limited response with pharmacologic therapy, percutaneous stent revascularization of the internal pudendal artery is feasible and is associated with clinically meaningful improvement in both subjective and objective measures of erectile function. (Safety and Feasibility of the Zotarolimus Stent in Treating Males With Erectile Dysfunction (ED) (ZEN); NCT01643200). (J Am Coll Cardiol 2012;60:2618-27) (C) 2012 by the American College of Cardiology Foundation C1 [Rocha-Singh, Krishna J.] St Johns Hosp, Prairie Vasc Inst, Springfield, IL 62701 USA. [Rogers, Jason H.] Univ Calif Davis, Med Ctr, Div Cardiovasc Med, Sacramento, CA 95817 USA. [Goldstein, Irwin] Alvarado Hosp, San Diego, CA USA. [Kandzari, David E.] Piedmont Heart Inst, Dept Intervent Cardiol, Atlanta, GA USA. [Koehler, Tobias S.] So Illinois Univ, Sch Med, Div Urol, Springfield, IL USA. [Stinis, Curtiss T.] Scripps Clin, Div Cardiol, La Jolla, CA 92037 USA. [Wagner, Paula J.] Univ Calif Davis, Med Ctr, Div Urol Surg, Sacramento, CA 95817 USA. [Popma, Jeffrey J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Cardiovasc Div,Dept Internal Med, Boston, MA 02215 USA. [Jaff, Michael R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vasc Ctr, Boston, MA USA. RP Rocha-Singh, KJ (reprint author), St Johns Hosp, Prairie Vasc Inst, 619 E Mason St, Springfield, IL 62701 USA. EM ksingh@prairieheart.com FU Medtronic Cardiovascular, Santa Rosa, California; Medtronic; American Medical Systems; Abbott; Hollister FX The ZEN trial was funded by Medtronic Cardiovascular, Santa Rosa, California. Dr. Rogers is a consultant for Medtronic. Dr. Goldstein is a consultant for, and receives honoraria from Medtronic. Dr. Kandzari receives research/grant support and consulting honoraria from Medtronic. Dr. Kohler receives research/grant funding from American Medical Systems, Medtronic, Abbott, and Hollister; is a consultant for Medtronic, Actient, American Medical Systems, Coloplast; and is a speaker for Auxilium and Allergan. Dr. Stinis is a consultant for Medtronic, Abbott Vascular, Edwards Lifesciences, and Cook Medical. Dr. Popma is a consultant for and receives research grants from Medtronic. Dr. Jaff is a consultant for Medtronic. Dr. Rocha-Singh is a consultant of Medtronic. Ms. Wagner has reported that she has no relationships relevant to the contents of this paper to disclose. NR 38 TC 17 Z9 18 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 25 PY 2012 VL 60 IS 25 BP 2618 EP 2627 DI 10.1016/j.jacc.2012.08.1016 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 056YG UT WOS:000312527000004 PM 23177300 ER PT J AU Reynolds, MR Magnuson, EA Lei, Y Wang, KJ Vilain, K Li, HY Walczak, J Pinto, DS Thourani, VH Svensson, LG Mack, MJ Miller, DC Satler, LE Bavaria, J Smith, CR Leon, MB Cohen, DJ AF Reynolds, Matthew R. Magnuson, Elizabeth A. Lei, Yang Wang, Kaijun Vilain, Katherine Li, Haiyan Walczak, Joshua Pinto, Duane S. Thourani, Vinod H. Svensson, Lars G. Mack, Michael J. Miller, D. Craig Satler, Lowell E. Bavaria, Joseph Smith, Craig R. Leon, Martin B. Cohen, David J. CA PARTNER Investigators TI Cost-Effectiveness of Transcatheter Aortic Valve Replacement Compared With Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis Results of the PARTNER (Placement of Aortic Transcatheter Valves) Trial (Cohort A) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE aortic valve replacement; cost-effectiveness; TAVR ID ECONOMIC-EVALUATION; CLINICAL-TRIAL; IMPLANTATION; OUTCOMES; ALONGSIDE; MODEL AB Objectives The aim of this study was to evaluate the cost-effectiveness of transcatheter aortic valve replacement (TAVR) compared with surgical aortic valve replacement (AVR) for patients with severe aortic stenosis and high surgical risk. Background TAVR is an alternative to AVR for patients with severe aortic stenosis and high surgical risk. Methods We performed a formal economic analysis based on cost, quality of life, and survival data collected in the PARTNER A (Placement of Aortic Transcatheter Valves) trial in which patients with severe aortic stenosis and high surgical risk were randomized to TAVR or AVR. Cumulative 12-month costs (assessed from a U. S. societal perspective) and quality-adjusted life-years (QALYs) were compared separately for the transfemoral (TF) and transapical (TA) cohorts. Results Although 12-month costs and QALYs were similar for TAVR and AVR in the overall population, there were important differences when results were stratified by access site. In the TF cohort, total 12-month costs were slightly lower with TAVR and QALYs were slightly higher such that TF-TAVR was economically dominant compared with AVR in the base case and economically attractive (incremental cost-effectiveness ratio <$50,000/QALY) in 70.9% of bootstrap replicates. In the TA cohort, 12-month costs remained substantially higher with TAVR, whereas QALYs tended to be lower such that TA-TAVR was economically dominated by AVR in the base case and economically attractive in only 7.1% of replicates. Conclusions In the PARTNER trial, TAVR was an economically attractive strategy compared with AVR for patients suitable for TF access. Future studies are necessary to determine whether improved experience and outcomes with TA-TAVR can improve its cost-effectiveness relative to AVR. (THE PARTNER TRIAL: Placement of AoRTic TraNscathetER Valve Trial; NCT00530894) (J Am Coll Cardiol 2012;60:2683-92) (C) 2012 by the American College of Cardiology Foundation C1 [Cohen, David J.] Univ Missouri, Sch Med, St Lukes Mid Amer Heart Inst, Kansas City, MO 64108 USA. [Reynolds, Matthew R.; Walczak, Joshua] Harvard Clin Res Inst, Boston, MA USA. [Reynolds, Matthew R.] Boston VA Healthcare Syst, Boston, MA USA. [Lei, Yang] Univ Kansas, Sch Med, Kansas City, KS USA. [Thourani, Vinod H.] Emory Univ, Sch Med, Atlanta, GA USA. [Svensson, Lars G.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Mack, Michael J.] Heart Hosp Baylor, Dallas, TX USA. [Miller, D. Craig] Stanford Univ, Palo Alto, CA 94304 USA. [Satler, Lowell E.] Washington Hosp Ctr, Washington, DC 20010 USA. [Bavaria, Joseph] Univ Penn, Philadelphia, PA 19104 USA. [Pinto, Duane S.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Smith, Craig R.; Leon, Martin B.] Columbia Presbyterian Med Ctr, New York, NY USA. RP Cohen, DJ (reprint author), Univ Missouri, Sch Med, St Lukes Mid Amer Heart Inst, 4401 Wornall Rd, Kansas City, MO 64108 USA. EM dcohen@saint-lukes.org FU Edwards Lifesciences; Medtronic; Abbott Vascular; National Institutes of Health [HL67025]; GenTAC Scientific Advisory Oversight Board; Boston Scientific; AstraZeneca; Eli Lilly FX Supported by Edwards Lifesciences, Inc. Dr. Reynolds receives research grant support from Edwards Lifesciences; and is a consultant for Medtronic. Dr. Pinto is a consultant to Medtronic, Inc. Dr. Thourani is a member of the Advisory Boards of Edwards Lifesciences, Sorin Medical, and St. Jude Medical; and receives research grant support from Edwards Lifesciences. Drs. Svensson and Leon have received travel reimbursements from Edwards Lifesciences related to their participation as members of the Executive Committee of the PARTNER Trial. Dr. Miller is a consultant to Edwards Lifesciences Inc.; and has received research grant support from Medtronic, Abbott Vascular, and a grant from the National Institutes of Health (grant HL67025), and from the GenTAC Scientific Advisory Oversight Board. Dr. Satler has received research grants from Edwards Lifesciences. Dr. Cohen has received research grants from Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, AstraZeneca, and Eli Lilly; is a consultant for Medtronic and Abbott Vascular; and has received speaking honoraria from Eli Lilly. Dr. Bavaria is a principal investigator for Edwards. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 24 TC 79 Z9 81 U1 1 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 25 PY 2012 VL 60 IS 25 BP 2683 EP 2692 DI 10.1016/j.jacc.2012.09.018 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 056YG UT WOS:000312527000015 PM 23122802 ER PT J AU McGill, LA Ismail, TF Nielles-Vallespin, S Ferreira, P Scott, AD Roughton, M Kilner, PJ Ho, SY McCarthy, KP Gatehouse, PD de Silva, R Speier, P Feiweier, T Mekkaoui, C Sosnovik, DE Prasad, SK Firmin, DN Pennell, DJ AF McGill, Laura-Ann Ismail, Tevfik F. Nielles-Vallespin, Sonia Ferreira, Pedro Scott, Andrew D. Roughton, Michael Kilner, Philip J. Ho, S. Yen McCarthy, Karen P. Gatehouse, Peter D. de Silva, Ranil Speier, Peter Feiweier, Thorsten Mekkaoui, Choukkri Sosnovik, David E. Prasad, Sanjay K. Firmin, David N. Pennell, Dudley J. TI Reproducibility of in-vivo diffusion tensor cardiovascular magnetic resonance in hypertrophic cardiomyopathy SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Article DE Hypertrophic cardiomyopathy; Diffusion tensor imaging; Diffusion weighted imaging; Cardiovascular magnetic resonance; Disarray ID MUSCLE CELL DISORGANIZATION; LEFT-VENTRICULAR MYOCARDIUM; ENGINEERING MECHANICS; DIASTOLIC FUNCTION; SUCCESSIVE STATES; HEART-ASSOCIATION; FIBER DISARRAY; TASK-FORCE; DIAGNOSIS; WALL AB Background: Myocardial disarray is an important histological feature of hypertrophic cardiomyopathy (HCM) which has been studied post-mortem, but its in-vivo prevalence and extent is unknown. Cardiac Diffusion Tensor Imaging (cDTI) provides information on mean intravoxel myocyte orientation and potentially myocardial disarray. Recent technical advances have improved in-vivo cDTI, and the aim of this study was to assess the interstudy reproducibility of quantitative in-vivo cDTI in patients with HCM. Methods and results: A stimulated-echo single-shot-EPI sequence with zonal excitation and parallel imaging was implemented. Ten patients with HCM were each scanned on 2 different days. For each scan 3 short axis mid-ventricular slices were acquired with cDTI at end systole. Fractional anisotropy (FA), mean diffusivity (MD), and helix angle (HA) maps were created using a cDTI post-processing platform developed in-house. The mean +/- SD global FA was 0.613 +/- 0.044, MD was 0.750 +/- 0.154 x 10(-3) mm(2)/s and HA was epicardium -34.3 +/- 7.6 degrees, mesocardium 3.5 +/- 6.9 degrees and endocardium 38.9 +/- 8.1 degrees. Comparison of initial and repeat studies showed global interstudy reproducibility for FA (SD = +/- 0.045, Coefficient of Variation (CoV) = 7.2%), MD (SD = +/- 0.135 x 10(-3) mm(2)/s, CoV = 18.6%) and HA (epicardium SD = +/- 4.8 degrees; mesocardium SD = +/- 3.4 degrees; endocardium SD = +/- 2.9 degrees). Reproducibility of FA was superior to MD (p = 0.003). Global MD was significantly higher in the septum than the reference lateral wall (0.784 +/- 0.188 vs 0.750 +/- 0.154 x10(-3) mm(2)/s, p < 0.001). Septal HA was significantly lower than the reference lateral wall in all 3 transmural layers (from -8.3 degrees to -10.4 degrees, all p < 0.001). Conclusions: To the best of our knowledge, this is the first study to assess the interstudy reproducibility of DTI in the human HCM heart in-vivo and the largest cDTI study in HCM to date. Our results show good reproducibility of FA, MD and HA which indicates that current technology yields robust in-vivo measurements that have potential clinical value. The interpretation of regional differences in the septum requires further investigation. C1 [McGill, Laura-Ann; Ismail, Tevfik F.; Nielles-Vallespin, Sonia; Ferreira, Pedro; Scott, Andrew D.; Roughton, Michael; Kilner, Philip J.; Ho, S. Yen; McCarthy, Karen P.; Gatehouse, Peter D.; de Silva, Ranil; Prasad, Sanjay K.; Firmin, David N.; Pennell, Dudley J.] Royal Brompton Hosp, Cardiovasc Magnet Resonance Unit, London SW3 6NP, England. [McGill, Laura-Ann; Nielles-Vallespin, Sonia; Ferreira, Pedro; Scott, Andrew D.; Kilner, Philip J.; Ho, S. Yen; McCarthy, Karen P.; de Silva, Ranil; Prasad, Sanjay K.; Firmin, David N.; Pennell, Dudley J.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. [Nielles-Vallespin, Sonia] NHLBI, NIH, DHHS, Bethesda, MD 20892 USA. [Speier, Peter; Feiweier, Thorsten] Siemens AG Med Solut, MR R&D, Erlangen, Germany. [Mekkaoui, Choukkri; Sosnovik, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Boston, MA USA. RP Firmin, DN (reprint author), Royal Brompton Hosp, Cardiovasc Magnet Resonance Unit, Sydney St, London SW3 6NP, England. EM d.firmin@imperial.ac.uk OI Gatehouse, Peter/0000-0002-0260-4719 FU National Institute of Health Research Cardiovascular Biomedical Research Unit at the Royal Brompton Hospital London; Imperial College, London; British Heart Foundation FX This work was supported by the National Institute of Health Research Cardiovascular Biomedical Research Unit at the Royal Brompton Hospital and Imperial College, London. Dr Ismail is funded by the British Heart Foundation. NR 40 TC 33 Z9 33 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1097-6647 J9 J CARDIOVASC MAGN R JI J. Cardiov. Magn. Reson. PD DEC 24 PY 2012 VL 14 AR 86 DI 10.1186/1532-429X-14-86 PG 15 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 096BB UT WOS:000315377600001 PM 23259835 ER PT J AU Robertson, D Diedrich, A Chapleau, MW AF Robertson, David Diedrich, Andre Chapleau, Mark W. TI Editorial on Arterial Baroreflex Issue SO AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL LA English DT Editorial Material ID MALIGNANT VAGOTONIA; BLOOD-PRESSURE; FAILURE; HYPERTENSION C1 [Robertson, David; Diedrich, Andre] Vanderbilt Univ, Dept Med, Div Clin Pharmacol, Auton Dysfunct Ctr, Nashville, TN 37203 USA. [Diedrich, Andre] Vanderbilt Univ, Dept Biomed Engn, Nashville, TN 37235 USA. [Chapleau, Mark W.] Univ Iowa, Dept Internal Med & Mol Physiol, Iowa City, IA USA. [Chapleau, Mark W.] Univ Iowa, Dept Biophys, Iowa City, IA USA. [Chapleau, Mark W.] US Dept Vet Affairs, Iowa City, IA USA. RP Robertson, D (reprint author), Vanderbilt Univ, Dept Med, Div Clin Pharmacol, Auton Dysfunct Ctr, Nashville, TN 37203 USA. EM david.robertson@vanderbilt.edu; andre.diedrich@vanderbilt.edu; mark-chapleau@uiowa.edu FU BLRD VA [I01 BX001414]; NHLBI NIH HHS [P01 HL014388, P01 HL056693] NR 13 TC 9 Z9 9 U1 2 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1566-0702 J9 AUTON NEUROSCI-BASIC JI Auton. Neurosci-Basic Clin. PD DEC 24 PY 2012 VL 172 IS 1-2 SI SI BP 1 EP 3 DI 10.1016/j.autneu.2012.10.010 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 062JA UT WOS:000312914700001 PM 23167992 ER PT J AU Gregory, K Tse, JY Wu, R Lewandrowski, K AF Gregory, Kimberly Tse, Julie Y. Wu, Roseann Lewandrowski, Kent TI Implementation of an expanded point-of-care testing (POCT) site inspection checklist in a large academic medical center: Implications for the management of a POCT program SO CLINICA CHIMICA ACTA LA English DT Article DE Point of care testing; Near patient testing; Regulatory compliance; Site inspections ID QUALITY AB Background: Management of point-of-care testing (POCT) continues to present challenges. The use of site inspections by POCT coordinators has been a mainstay for maintaining regulatory compliance in POCT although this process is labor intensive. Improvements in device design and the use of POCT data management systems have improved the ability of hospitals to manage POCT programs. Given these developments, using regular site inspections to ensure regulatory compliance of POCT may be less relevant than in the past. Methods: We implemented an expanded POCT site inspection checklist modeled after the requirements of the Joint Commission. The checklist included categories not specifically related to POCT such as the environment of care and safety. Results: The average number of deficiencies per site in 2011 was 2.37 (range 0-10) out of a possible 42. Only 18% of site inspections produced no citations. In contrast in 2010 the average number of deficiencies per site was 3.17 (out of a possible 32) and only 8.7% of sites had no citations. The difference in the number of deficiencies per site was significant (t-test two tailed p = 0.04). The most frequently cited deficiencies (24.2%) related to safety followed by maintenance of proper procedures and documentation of competency assessment. Conclusions: Despite improvements in many FOCI devices and data management systems, regular site inspections are still required to identify regulatory deficiencies and improve testing quality. The use of an expanded site inspection checklist will identify many areas for improvement that are not specifically related to POCT alone. (C) 2012 Elsevier B.V. All rights reserved. C1 [Gregory, Kimberly; Tse, Julie Y.; Wu, Roseann; Lewandrowski, Kent] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Tse, Julie Y.; Wu, Roseann; Lewandrowski, Kent] Harvard Univ, Sch Med, Boston, MA USA. RP Lewandrowski, K (reprint author), Massachusetts Gen Hosp, Dept Pathol, Gray 5 Chem,55 Fruit St, Boston, MA 02114 USA. EM klewandrowski@partners.org NR 9 TC 0 Z9 1 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD DEC 24 PY 2012 VL 414 BP 27 EP 33 DI 10.1016/j.cca.2012.07.015 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 059DU UT WOS:000312685400007 PM 22902708 ER PT J AU De Gasperi, R Sosa, MAG Elder, GA AF De Gasperi, Rita Sosa, Miguel A. Gama Elder, Gregory A. TI Presenilin-1 regulates the constitutive turnover of the fibronectin matrix in endothelial cells SO BMC BIOCHEMISTRY LA English DT Article DE Endothelial cells; Extracellular matrix; Fibronectin; Presenilin-1; Vascular development ID EXTRACELLULAR-MATRIX; ALZHEIMERS-DISEASE; TGF-BETA; INTEGRIN; EXPRESSION; MEMBRANE; MICE; LOCALIZATION; ACTIVATION; PROGENITOR AB Background: Presenilin-1 (PS1) is a transmembrane protein first discovered because of its association with familial Alzheimer's disease. Mice with null mutations in PS1 die shortly after birth exhibiting multiple CNS and non-CNS abnormalities. One of the most prominent features in the brains of PS1-/- embryos is a vascular dysgenesis that leads to multiple intracerebral hemorrhages. The molecular and cellular basis for the vascular dysgenesis in PS1-/- mice remains incompletely understood. Because the extracellular matrix plays key roles in vascular development we hypothesized that an abnormal extracellular matrix might be present in endothelial cells lacking PS1 and examined whether the lack of PS1 affects expression of fibronectin a component of the extracellular matrix known to be essential for vascular development. Results: We report that primary as well as continuously passaged PS1-/- endothelial cells contain more fibronectin than wild type cells and that the excess fibronectin in PS1-/- endothelial cells is incorporated into a fibrillar network. Supporting the in vivo relevance of this observation fibronectin expression was increased in microvascular preparations isolated from E14.5 to E18.5 PS1-/- embryonic brain. Reintroduction of PS1 into PS1-/- endothelial cells led to a progressive decrease in fibronectin levels showing that the increased fibronectin in PS1-/- endothelial cells was due to loss of PS1. Increases in fibronectin protein in PS1-/- endothelial cells could not be explained by increased levels of fibronectin RNA nor based on metabolic labeling studies by increased protein synthesis. Rather we show based on the rate of turnover of exogenously added biotinylated fibronectin that increased fibronectin in PS1-/- endothelial cells results from a slower degradation of the fibronectin fibrillar matrix on the cell surface. Conclusions: These studies show that PS1 regulates the constitutive turnover of the fibronectin matrix in endothelial cells. These studies provide molecular clues that may help to explain the origin of the vascular dysgenesis that develops in PS1-/- embryonic mice. C1 [Elder, Gregory A.] James J Peters Dept Vet Affairs Med Ctr, Neurol Serv, Bronx, NY 10468 USA. [De Gasperi, Rita; Sosa, Miguel A. Gama; Elder, Gregory A.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Elder, Gregory A.] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [De Gasperi, Rita; Sosa, Miguel A. Gama; Elder, Gregory A.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. RP Elder, GA (reprint author), James J Peters Dept Vet Affairs Med Ctr, Neurol Serv, Bronx, NY 10468 USA. EM gregory.elder@va.gov FU Department of Veterans Affairs [5I01BX000342-02] FX This work was supported by a Merit Award from the Department of Veterans Affairs (5I01BX000342-02). We thank Drs. Paul Mathews and Nikolaos Robakis for gifts of antibodies. NR 40 TC 2 Z9 2 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2091 J9 BMC BIOCHEM JI BMC Boichem. PD DEC 21 PY 2012 VL 13 AR 28 DI 10.1186/1471-2091-13-28 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 079ZW UT WOS:000314212000001 PM 23259730 ER PT J AU Schmedt, T Chen, YM Nguyen, TT Li, SM Bonanno, JA Jurkunas, UV AF Schmedt, Thore Chen, Yuming Nguyen, Tracy T. Li, Shimin Bonanno, Joseph A. Jurkunas, Ula V. TI Telomerase Immortalization of Human Corneal Endothelial Cells Yields Functional Hexagonal Monolayers SO PLOS ONE LA English DT Article ID CARBONIC-ANHYDRASE; CELLULAR SENESCENCE; MOLECULAR-MECHANISMS; CL-/HCO3-EXCHANGE; EPITHELIAL-CELLS; NEURAL CREST; EXPRESSION; TRANSPORT; LIFE; DONORS AB Human corneal endothelial cells (HCEnCs) form a monolayer of hexagonal cells whose main function is to maintain corneal clarity by regulating corneal hydration. HCEnCs are derived from neural crest and are arrested in the post-mitotic state. Thus cell loss due to aging or corneal endothelial disorders leads to corneal edema and blindness-the leading indication for corneal transplantation. Here we show the existence of morphologically distinct subpopulations of HCEnCs that are interspersed among primary cells and exhibit enhanced self-renewal competence and lack of phenotypic signs of cellular senescence. Colonies of these uniform and hexagonal HCEnCs (HCEnC-21) were selectively isolated and demonstrated high proliferative potential that was dependent on endogenous upregulation of telomerase and cyclin D/CDK4. Further transduction of HCEnC-21 with telomerase yielded a highly proliferative corneal endothelial cell line (HCEnT-21T) that was devoid of oncogenic transformation and retained critical corneal endothelial cell characteristics and functionality. This study will significantly impact the fields of corneal cell biology and regenerative medicine. C1 [Schmedt, Thore; Chen, Yuming; Jurkunas, Ula V.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Schepens Eye Res Inst, Boston, MA 02115 USA. [Nguyen, Tracy T.; Li, Shimin; Bonanno, Joseph A.] Indiana Univ, Sch Optometry, Bloomington, IN USA. RP Jurkunas, UV (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Schepens Eye Res Inst, Boston, MA 02115 USA. EM ula.jurkunas@schepens.harvard.edu FU National Institutes of Health/National Eye Institute [R01EY020581]; Massachusetts Lions Eye Research Fund FX This work was supported by National Institutes of Health/National Eye Institute R01EY020581 and Massachusetts Lions Eye Research Fund grants to UVJ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 52 TC 13 Z9 13 U1 0 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 21 PY 2012 VL 7 IS 12 AR e51427 DI 10.1371/journal.pone.0051427 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 065OW UT WOS:000313158800011 PM 23284695 ER PT J AU Rosenbluh, J Nijhawan, D Cox, AG Li, XN Neal, JT Schafer, EJ Zack, TI Wang, XX Tsherniak, A Schinzel, AC Shao, DD Schumacher, SE Weir, BA Vazquez, F Cowley, GS Root, DE Mesirov, JP Beroukhim, R Kuo, CJ Goessling, W Hahn, WC AF Rosenbluh, Joseph Nijhawan, Deepak Cox, Andrew G. Li, Xingnan Neal, James T. Schafer, Eric J. Zack, Travis I. Wang, Xiaoxing Tsherniak, Aviad Schinzel, Anna C. Shao, Diane D. Schumacher, Steven E. Weir, Barbara A. Vazquez, Francisca Cowley, Glenn S. Root, David E. Mesirov, Jill P. Beroukhim, Rameen Kuo, Calvin J. Goessling, Wolfram Hahn, William C. TI beta-Catenin-Driven Cancers Require a YAP1 Transcriptional Complex for Survival and Tumorigenesis SO CELL LA English DT Article ID YES-ASSOCIATED PROTEIN; HIPPO PATHWAY; CELL-PROLIFERATION; SIGNALING PATHWAY; ZEBRAFISH EMBRYOS; GROWTH-CONTROL; COLON-CANCER; ORGAN SIZE; PHOSPHORYLATION; ACTIVATION AB Wnt/beta-catenin signaling plays a key role in the pathogenesis of colon and other cancers; emerging evidence indicates that oncogenic beta-catenin regulates several biological processes essential for cancer initiation and progression. To decipher the role of beta-catenin in transformation, we classified beta-catenin activity in 85 cancer cell lines in which we performed genome-scale loss-of-function screens and found that beta-catenin active cancers are dependent on a signaling pathway involving the transcriptional regulator YAP1. Specifically, we found that YAP1 and the transcription factor TBX5 form a complex with beta-catenin. Phosphorylation of YAP1 by the tyrosine kinase YES1 leads to localization of this complex to the promoters of antiapoptotic genes, including BCL2L1 and BIRC5. A small-molecule inhibitor of YES1 impeded the proliferation of beta-catenin-dependent cancers in both cell lines and animal models. These observations define a beta-catenin-YAP1-TBX5 complex essential to the transformation and survival of beta-catenin-driven cancers. C1 [Rosenbluh, Joseph; Nijhawan, Deepak; Schafer, Eric J.; Wang, Xiaoxing; Schinzel, Anna C.; Shao, Diane D.; Weir, Barbara A.; Vazquez, Francisca; Goessling, Wolfram; Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Zack, Travis I.; Schumacher, Steven E.; Beroukhim, Rameen; Hahn, William C.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Rosenbluh, Joseph; Nijhawan, Deepak; Cox, Andrew G.; Schafer, Eric J.; Wang, Xiaoxing; Schinzel, Anna C.; Shao, Diane D.; Beroukhim, Rameen; Goessling, Wolfram; Hahn, William C.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Cox, Andrew G.; Goessling, Wolfram] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. [Rosenbluh, Joseph; Nijhawan, Deepak; Schafer, Eric J.; Zack, Travis I.; Wang, Xiaoxing; Tsherniak, Aviad; Schinzel, Anna C.; Shao, Diane D.; Schumacher, Steven E.; Weir, Barbara A.; Vazquez, Francisca; Cowley, Glenn S.; Root, David E.; Mesirov, Jill P.; Beroukhim, Rameen; Hahn, William C.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Cox, Andrew G.; Goessling, Wolfram] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Li, Xingnan; Neal, James T.; Kuo, Calvin J.] Stanford Univ, Sch Med, Div Hematol, Dept Med, Stanford, CA 94305 USA. [Zack, Travis I.] Harvard Univ, Program Biophys, Boston, MA 02115 USA. RP Hahn, WC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM william_hahn@dfci.harvard.edu RI Schumacher, Steven/E-9821-2013 OI Schumacher, Steven/0000-0002-6819-5647 FU NIH/NCI [R01 CA140545, RC2 CA148268, U54 CA143798, U01 DK085527, U01 CA151920, R01 DK085720, U54 CA112962, R01 DK090311]; Pew Charitable Trust; Fidelity Foundation; Stanford University; DoD [W81XWH-10-1-0062]; Conquer Cancer Foundation; Sass Foundation; SPORE career development award [P50 CA127003]; NIH [F32 GM090437] FX We thank the members of the Hahn lab for helpful discussions and L. Gafney and L. Solomon for assistance with graphic arts. This work was supported in part by NIH/NCI grants R01 CA140545 (W.C.H.), RC2 CA148268 (W.C.H.), U54 CA143798 (R.B.), U01 DK085527 (C.J.K.), U01 CA151920 (C.J.K.), R01 DK085720 (C.J.K.), U54 CA112962 (A.T., J.P.M., and W.C.H.), R01 DK090311 (W.G.), the Pew Charitable Trust (W.G.), a Fidelity Foundation grant (C.J.K.), a Stanford University Dean's Fellowship (J.T.N.), a DoD breast cancer postdoctoral fellowship W81XWH-10-1-0062 (X.W.), Conquer Cancer Foundation Young Investigator Award and Sass Foundation Fellowship (D.N.), a SPORE career development award P50 CA127003 (J.R.), and an NIH F32 postdoctoral fellowship F32 GM090437 (J.R.). J.R. is a John Svenson postdoctoral fellow. W.C.H. and R.B. are consultants for Novartis Pharmaceuticals. NR 58 TC 187 Z9 190 U1 5 U2 67 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD DEC 21 PY 2012 VL 151 IS 7 BP 1457 EP 1473 DI 10.1016/j.cell.2012.11.026 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 062AA UT WOS:000312890300012 PM 23245941 ER PT J AU Pos, W Sethi, DK Call, MJ Schulze, MSED Anders, AK Pyrdol, J Wucherpfennig, KW AF Pos, Wouter Sethi, Dhruv K. Call, Melissa J. Schulze, Monika-Sarah E. D. Anders, Anne-Kathrin Pyrdol, Jason Wucherpfennig, Kai W. TI Crystal Structure of the HLA-DM-HLA-DR1 Complex Defines Mechanisms for Rapid Peptide Selection SO CELL LA English DT Article ID HLA-DR MOLECULES; CLASS-II MHC; ANTIGEN PRESENTATION; INVARIANT-CHAIN; HISTOCOMPATIBILITY ANTIGEN; SURFACE EXPRESSION; DM SUSCEPTIBILITY; BINDING; MICE; DISSOCIATION AB HLA-DR molecules bind microbial peptides in an endosomal compartment and present them on the cell surface for CD4 T cell surveillance. HLA-DM plays a critical role in the endosomal peptide selection process. The structure of the HLA-DM-HLA-DR complex shows major rearrangements of the HLA-DR peptide-binding groove. Flipping of a tryptophan away from the HLA-DR1 P1 pocket enables major conformational changes that position hydrophobic HLA-DR residues into the P1 pocket. These conformational changes accelerate peptide dissociation and stabilize the empty HLA-DR peptide-binding groove. Initially, incoming peptides have access to only part of the HLA-DR groove and need to compete with HLA-DR residues for access to the P2 site and the hydrophobic P1 pocket. This energetic barrier creates a rapid and stringent selection process for the highest-affinity binders. Insertion of peptide residues into the P2 and P1 sites reverses the conformational changes, terminating selection through DM dissociation. C1 [Pos, Wouter; Sethi, Dhruv K.; Call, Melissa J.; Schulze, Monika-Sarah E. D.; Anders, Anne-Kathrin; Pyrdol, Jason; Wucherpfennig, Kai W.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Anders, Anne-Kathrin; Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Program Immunol, Boston, MA 02115 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM kai_wucherpfennig@dfci.harvard.edu FU National Institutes of Health [RO1 NS044914, PO1 AI045757]; National Multiple Sclerosis Society; American Diabetes Association; Ruth L. Kirschstein National Research Service Award; National Center for Research Resources [5P41RR015301-10]; National Institute of General Medical Sciences from the National Institutes of Health [8P41 GM103403-10]; U.S. DOE [DE-AC02-06CH11357] FX We would like to thank Drs. Eric Sundberg, Shannon Turley, Hao Wu, and Bana Jabri for reading the manuscript. This work was supported by grants from the National Institutes of Health (RO1 NS044914 and PO1 AI045757 to K.W.W.), postdoctoral fellowships from The National Multiple Sclerosis Society (D.K.S.) and the American Diabetes Association (W.P.), as well as a Ruth L. Kirschstein National Research Service Award (to M.J.C.). We thank the staff at the UCLA-DOE crystallization core and the CSIRO Collaborative Crystallization Centre, Melbourne, Australia, for setting up screens. Diffraction data were collected at the Advanced Photon Source using beamlines allocated to the Northeastern Collaborative Access Team. These beamlines are supported by grants from the National Center for Research Resources (5P41RR015301-10) and the National Institute of General Medical Sciences (8P41 GM103403-10) from the National Institutes of Health. Use of the Advanced Photon Source, an Office of Science User Facility operated for the U.S. Department of Energy (DOE) Office of Science by Argonne National Laboratory, was supported by the U.S. DOE under Contract No. DE-AC02-06CH11357. NR 57 TC 52 Z9 52 U1 2 U2 28 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD DEC 21 PY 2012 VL 151 IS 7 BP 1557 EP 1568 DI 10.1016/j.cell.2012.11.025 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 062AA UT WOS:000312890300019 PM 23260142 ER PT J AU Polo, JM Anderssen, E Walsh, RM Schwarz, BA Nefzger, CM Lim, SM Borkent, M Apostolou, E Alaei, S Cloutier, J Bar-Nur, O Cheloufi, S Stadtfeld, M Figueroa, ME Robinton, D Natesan, S Melnick, A Zhu, JF Ramaswamy, S Hochedlinger, K AF Polo, Jose M. Anderssen, Endre Walsh, Ryan M. Schwarz, Benjamin A. Nefzger, Christian M. Lim, Sue Mei Borkent, Marti Apostolou, Effie Alaei, Sara Cloutier, Jennifer Bar-Nur, Ori Cheloufi, Sihem Stadtfeld, Matthias Figueroa, Maria Eugenia Robinton, Daisy Natesan, Sridaran Melnick, Ari Zhu, Jinfang Ramaswamy, Sridhar Hochedlinger, Konrad TI A Molecular Roadmap of Reprogramming Somatic Cells into iPS Cells SO CELL LA English DT Article ID PLURIPOTENT STEM-CELLS; MOUSE; EXPRESSION; FIBROBLASTS; INDUCTION; DISCOVERY AB Factor-induced reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) is inefficient, complicating mechanistic studies. Here, we examined defined intermediate cell populations poised to becoming iPSCs by genome-wide analyses. We show that induced pluripotency elicits two transcriptional waves, which are driven by c-Myc/Klf4 (first wave) and Oct4/Sox2/Klf4 (second wave). Cells that become refractory to reprogramming activate the first but fail to initiate the second transcriptional wave and can be rescued by elevated expression of all four factors. The establishment of bivalent domains occurs gradually after the first wave, whereas changes in DNA methylation take place after the second wave when cells acquire stable pluripotency. This integrative analysis allowed us to identify genes that act as roadblocks during reprogramming and surface markers that further enrich for cells prone to forming iPSCs. Collectively, our data offer new mechanistic insights into the nature and sequence of molecular events inherent to cellular reprogramming. C1 [Polo, Jose M.; Anderssen, Endre; Walsh, Ryan M.; Schwarz, Benjamin A.; Borkent, Marti; Apostolou, Effie; Cloutier, Jennifer; Bar-Nur, Ori; Cheloufi, Sihem; Stadtfeld, Matthias; Robinton, Daisy; Ramaswamy, Sridhar; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Polo, Jose M.; Anderssen, Endre; Walsh, Ryan M.; Schwarz, Benjamin A.; Borkent, Marti; Apostolou, Effie; Cloutier, Jennifer; Bar-Nur, Ori; Cheloufi, Sihem; Stadtfeld, Matthias; Robinton, Daisy; Ramaswamy, Sridhar; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Polo, Jose M.; Anderssen, Endre; Walsh, Ryan M.; Schwarz, Benjamin A.; Borkent, Marti; Apostolou, Effie; Cloutier, Jennifer; Bar-Nur, Ori; Cheloufi, Sihem; Stadtfeld, Matthias; Robinton, Daisy; Ramaswamy, Sridhar; Hochedlinger, Konrad] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Polo, Jose M.; Nefzger, Christian M.; Lim, Sue Mei; Alaei, Sara] Monash Univ, Monash Immunol & Stem Cell Labs, Clayton, Vic 3800, Australia. [Polo, Jose M.] Monash Univ, Australian Regenerat Med Inst, Clayton, Vic 3800, Australia. [Anderssen, Endre; Ramaswamy, Sridhar] Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Borkent, Marti] Erasmus MC, Dept Reprod & Dev, NL-3015 GE Rotterdam, Netherlands. [Figueroa, Maria Eugenia; Melnick, Ari] Weill Cornell Med Coll, Dept Med, Div Hematol Oncol, New York, NY 10065 USA. [Natesan, Sridaran] Sanofi Aventis, Cambridge, MA 02139 USA. [Zhu, Jinfang] NIAID, NIH, Bethesda, MD 20892 USA. [Hochedlinger, Konrad] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Hochedlinger, Konrad] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Hochedlinger, Konrad] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Ramaswamy, S (reprint author), Massachusetts Gen Hosp, Ctr Canc, 185 Cambridge St, Boston, MA 02114 USA. EM sridhar@mgh.harvard.edu; khochedlinger@helix.mgh.harvard.edu RI Zhu, Jinfang/B-7574-2012; OI Polo, Jose M/0000-0002-2531-778X; Stadtfeld, Matthias/0000-0002-5852-9906; Alaei, Sara/0000-0003-4897-6339 FU ECOR postdoctoral fellowship; Monash Larkins Program; NHMRC CDF; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, USA; NIH [DP2OD003266, R01HD058013]; HHMI FX We thank members of the Hochedlinger and Ramaswamy labs for helpful suggestions and critical reading of the manuscript. We thank Laura Prickett and Kat Folz-Donahue at the MGH/HSCI flow cytometry core and Flowcore Monash for expert cell sorting; Paul Lacaze, Danielle Evans, and Michelle Garred at Millenium Science for support with the Fluidigm experiments; and Lucy Dagostino from Lifetech Australia for help in miRNA assays. We are grateful to Ben Wittner for help with formatting and uploading genome-wide data. Support to J.M.P. was from an ECOR postdoctoral fellowship, Monash Larkins Program, and a NHMRC CDF. J.Z. was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, USA. K.H. was supported by the NIH (DP2OD003266 and R01HD058013). S.R. was supported by an HHMI Physican-Scientist Early Career Award. NR 26 TC 312 Z9 320 U1 17 U2 133 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD DEC 21 PY 2012 VL 151 IS 7 BP 1617 EP 1632 DI 10.1016/j.cell.2012.11.039 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 062AA UT WOS:000312890300024 PM 23260147 ER PT J AU De Meyer, SF Savchenko, AS Haas, MS Schatzberg, D Carroll, MC Schiviz, A Dietrich, B Rottensteiner, H Scheiflinger, F Wagner, DD AF De Meyer, Simon F. Savchenko, Alexander S. Haas, Michael S. Schatzberg, Daphne Carroll, Michael C. Schiviz, Alexandra Dietrich, Barbara Rottensteiner, Hanspeter Scheiflinger, Friedrich Wagner, Denisa D. TI Protective anti-inflammatory effect of ADAMTS13 on myocardial ischemia/reperfusion injury in mice SO BLOOD LA English DT Article ID VON-WILLEBRAND-FACTOR; THROMBOTIC-THROMBOCYTOPENIC PURPURA; ISCHEMIA-REPERFUSION INJURY; LONG-TERM MORTALITY; NEUTROPHIL DEPLETION; LYMPHOCYTE RATIO; CORONARY THROMBI; TISSUE FACTOR; IN-VIVO; INFARCTION AB Coronary heart disease is a major cause of death in the western world. Although essential for successful recovery, reperfusion of ischemic myocardium is inevitably associated with reperfusion injury. To investigate a potential protective role of ADAMTS13, a protease cleaving von Willebrand factor multimers, during myocardial ischemia/reperfusion, we used a mouse model of acute myocardial infarction. We found that Adamts13(-/-) mice developed larger myocardial infarctions than wild-type control mice, whereas treatment of wild-type mice with recombinant human ADAMTS13 (rhADAMTS13) led to smaller infarctions. The protective effect of ADAMTS13 was further confirmed by a significant reduction of cardiac troponin-I release and less myocardial apoptosis in mice that received rhADAMTS13 compared with controls. Platelets adherent to the blood vessel wall were observed in few areas in the heart samples from mice treated with vehicle and were not detected in samples from mice treated with rhADAMTS13. However, we observed a 9-fold reduction in number of neutrophils infiltrating ischemic myocardium in mice that were treated with rhADAMTS13, suggesting a potent anti-inflammatory effect of ADAMTS13 during heart injury. Our data show that ADAMTS13 reduces myocardial ischemia/reperfusion injury in mice and indicate that rhADAMTS13 could be of therapeutic value to limit myocardial ischemia/reperfusion injury. (Blood. 2012; 120(26): 5217-5223) C1 [Wagner, Denisa D.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [De Meyer, Simon F.; Savchenko, Alexander S.; Schatzberg, Daphne; Carroll, Michael C.; Wagner, Denisa D.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [De Meyer, Simon F.; Savchenko, Alexander S.; Carroll, Michael C.; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [De Meyer, Simon F.] KU Leuven Campus Kortrijk, Lab Thrombosis Res, Kortrijk, Belgium. [Haas, Michael S.] DecImmune Therapeut, Cambridge, MA USA. [Schiviz, Alexandra; Dietrich, Barbara; Rottensteiner, Hanspeter; Scheiflinger, Friedrich] Baxter Innovat GmbH, Vienna, Austria. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, 3 Blackfan Cir,3rd Fl, Boston, MA 02115 USA. EM wagner@idi.harvard.edu FU National Heart, Lung, and Blood Institute of the National Institutes of Health [R01 HL041002]; Baxter Biosciences FX This work was supported by National Heart, Lung, and Blood Institute of the National Institutes of Health grant R01 HL041002 (to D. D. W.) and a basic research grant from Baxter Biosciences to support animal housing. NR 40 TC 39 Z9 40 U1 0 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 20 PY 2012 VL 120 IS 26 BP 5217 EP 5223 DI 10.1182/blood-2012-06-439935 PG 7 WC Hematology SC Hematology GA 065CB UT WOS:000313123900023 PM 22915644 ER PT J AU Mrozek, K Marcucci, G Nicolet, D Maharry, KS Becker, H Whitman, SP Metzeler, KH Schwind, S Wu, YZ Kohlschmidt, J Pettenati, MJ Heerema, NA Block, AW Patil, SR Baer, MR Kolitz, JE Moore, JO Carroll, AJ Stone, RM Larson, RA Bloomfield, CD AF Mrozek, Krzysztof Marcucci, Guido Nicolet, Deedra Maharry, Kati S. Becker, Heiko Whitman, Susan P. Metzeler, Klaus H. Schwind, Sebastian Wu, Yue-Zhong Kohlschmidt, Jessica Pettenati, Mark J. Heerema, Nyla A. Block, AnneMarie W. Patil, Shivanand R. Baer, Maria R. Kolitz, Jonathan E. Moore, Joseph O. Carroll, Andrew J. Stone, Richard M. Larson, Richard A. Bloomfield, Clara D. TI Prognostic Significance of the European LeukemiaNet Standardized System for Reporting Cytogenetic and Molecular Alterations in Adults With Acute Myeloid Leukemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MICRORNA-EXPRESSION SIGNATURES; INTERNAL TANDEM DUPLICATION; ACUTE MYELOGENOUS LEUKEMIA; SINGLE CEBPA MUTATIONS; AGE 60 YEARS; GROUP-B; FAVORABLE PROGNOSIS; NPM1 MUTATIONS; YOUNGER ADULTS; OLDER PATIENTS AB Purpose To evaluate the prognostic significance of the international European LeukemiaNet (ELN) guidelines for reporting genetic alterations in acute myeloid leukemia (AML). Patients and Methods We analyzed 1,550 adults with primary AML, treated on Cancer and Leukemia Group B first-line trials, who had pretreatment cytogenetics and, for cytogenetically normal patients, mutational status of NPM1, CEBPA, and FLT3 available. We compared complete remission (CR) rates, disease-free survival (DFS), and overall survival (OS) among patients classified into the four ELN genetic groups (favorable, intermediate-I, intermediate-II, adverse) separately for 818 younger (age < 60 years) and 732 older (age >= 60 years) patients. Results The percentages of younger versus older patients in the favorable (41% v 20%; P<.001), intermediate-II (19% v 30%; P<.001), and adverse (22% v 31%; P<.001) genetic groups differed. The favorable group had the best and the adverse group the worst CR rates, DFS, and OS in both age groups. Both intermediate groups had significantly worse outcomes than the favorable but better than the adverse group. Intermediate-I and intermediate-II groups in older patients had similar outcomes, whereas the intermediate-II group in younger patients had better OS but not better CR rates or DFS than the intermediate-I group. The prognostic significance of ELN classification was confirmed by multivariable analyses. For each ELN group, older patients had worse outcomes than younger patients. Conclusion The ELN classification clearly separates the genetic groups by outcome, supporting its use for risk stratification in clinical trials. Because they have different proportions of genetic alterations and outcomes, younger and older patients should be reported separately when using the ELN classification. J Clin Oncol 30:4515-4523. (C) 2012 by American Society of Clinical Oncology C1 [Mrozek, Krzysztof; Marcucci, Guido; Nicolet, Deedra; Maharry, Kati S.; Becker, Heiko; Whitman, Susan P.; Metzeler, Klaus H.; Schwind, Sebastian; Wu, Yue-Zhong; Kohlschmidt, Jessica; Bloomfield, Clara D.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Nicolet, Deedra; Maharry, Kati S.; Kohlschmidt, Jessica] Mayo Clin, Alliance Clin Trials Oncol Stat, Rochester, MN USA. [Nicolet, Deedra; Maharry, Kati S.; Kohlschmidt, Jessica] Mayo Clin, Ctr Data, Rochester, MN USA. [Pettenati, Mark J.] Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27109 USA. [Moore, Joseph O.] Duke Univ, Med Ctr, Durham, NC USA. [Block, AnneMarie W.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Kolitz, Jonathan E.] Hofstra N Shore Long Isl Jewish Sch Med, Monter Canc Ctr, Lake Success, NY USA. [Patil, Shivanand R.] Univ Iowa, Iowa City, IA USA. [Baer, Maria R.] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Carroll, Andrew J.] Univ Alabama Birmingham, Birmingham, AL USA. [Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Larson, Richard A.] Univ Chicago, Chicago, IL 60637 USA. RP Mrozek, K (reprint author), Ohio State Univ, James Canc Hosp, Ctr Comprehens Canc, Room 1232A,300 W 10th Ave, Columbus, OH 43210 USA. EM krzysztof.mrozek@osumc.edu RI Metzeler, Klaus/C-2118-2009; Mrozek, Krzysztof/A-3142-2008; OI Metzeler, Klaus/0000-0003-3920-7490; Larson, Richard/0000-0001-9168-3203 FU National Cancer Institute, Bethesda, MD [CA101140, CA114725, CA140158, CA31946, CA33601, CA16058, CA77658, CA129657]; Coleman Leukemia Research Foundation; Deutsche Krebshilfe-Dr. Mildred Scheel Cancer Foundation; Novartis; Ariad FX Supported in part by Grants No. CA101140, CA114725, CA140158, CA31946, CA33601, CA16058, CA77658, and CA129657 from the National Cancer Institute, Bethesda, MD; The Coleman Leukemia Research Foundation; and the Deutsche Krebshilfe-Dr. Mildred Scheel Cancer Foundation (H.B.).; Although all authors completed the disclosure declaration, the following author(s) and/or an author's immediate family member(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors. Employment or Leadership Position: None Consultant or Advisory Role: Joseph O. Moore, Novartis (C) Stock Ownership: None Honoraria: Joseph O. Moore, Novartis Research Funding: Joseph O. Moore, Novartis, Ariad Expert Testimony: None Other Remuneration: None NR 52 TC 138 Z9 147 U1 0 U2 14 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 20 PY 2012 VL 30 IS 36 BP 4515 EP 4523 DI 10.1200/JCO.2012.43.4738 PG 9 WC Oncology SC Oncology GA 060YT UT WOS:000312815000018 PM 22987078 ER PT J AU Fernandez, CV Ruccione, K Wells, RJ Long, JB Pelletier, W Hooke, MC Pentz, RD Noll, RB Baker, JN O'Leary, M Reaman, G Adamson, PC Joffe, S AF Fernandez, Conrad V. Ruccione, Kathleen Wells, Robert J. Long, Jay B. Pelletier, Wendy Hooke, Mary C. Pentz, Rebecca D. Noll, Robert B. Baker, Justin N. O'Leary, Maura Reaman, Gregory Adamson, Peter C. Joffe, Steven TI Recommendations for the Return of Research Results to Study Participants and Guardians: A Report From the Children's Oncology Group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CLINICAL-TRIAL; INFORMED-CONSENT; CANCER; ATTITUDES; MEDIA; ADOLESCENTS; SURVIVORS; COVERAGE; MEETINGS; PARENTS AB Purpose The Children's Oncology Group (COG) strongly supports the widely recognized principle that research participants should be offered a summary of study results. The mechanism by which to do so in a cooperative research group setting has not been previously described. Methods On the basis of a review of the available empirical and theoretic literature and on iterative, multidisciplinary discussion, a COG Return of Results Task Force (RRTF) offered detailed recommendations for the return of results to research study participants. Results The RRTF established guidelines for the notification of research participants and/or their parents/guardians about the availability of research results, a mechanism for and timing of sharing results via registration on the COG public Web site, the scope of the research to be shared, the target audience, and a process for creating and vetting lay summaries of study results. The RRTF recognized the challenges in adequately conveying complex scientific results to audiences with varying levels of health literacy and recommended that particularly sensitive or complex results be returned using direct personal contact. The RRTF also recommended evaluation of the cost, effectiveness, and impact of sharing results. Conclusion These recommendations provide a framework for the offering and returning of results to participants. They can be used by individual investigators, multi-investigator research collaboratives, and large cooperative groups. J Clin Oncol 30:4573-4579. (C) 2012 by American Society of Clinical Oncology C1 [Fernandez, Conrad V.] Dalhousie Univ, Izaak Walton Killam Hlth Ctr, Halifax, NS, Canada. [Pelletier, Wendy] Alberta Childrens Prov Gen Hosp, Calgary, AB T2T 5C7, Canada. [Ruccione, Kathleen] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Long, Jay B.] Miller Childrens Hosp Long Beach, Long Beach, CA USA. [Wells, Robert J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Hooke, Mary C.] Univ Minnesota, Sch Nursing, Minneapolis, MN 55455 USA. [Pentz, Rebecca D.] Emory Univ, Sch Med, Atlanta, GA USA. [Noll, Robert B.] Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. [Adamson, Peter C.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Baker, Justin N.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [O'Leary, Maura] US FDA, Rockville, MD 20857 USA. [Reaman, Gregory] George Washington Univ, Sch Med & Hlth Sci, Childrens Natl Med Ctr, Washington, DC 20052 USA. [Joffe, Steven] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA. [Joffe, Steven] Harvard Univ, Sch Med, Boston, MA USA. RP Fernandez, CV (reprint author), Dalhousie Univ, 5850 Univ Ave, Halins, NS B3K 6R8, Canada. EM conrad.fernandez@iwk.nshealth.ca OI Joffe, Steven/0000-0002-0667-7384 FU Children's Oncology Group, National Cancer Institute, National Institutes of Health, Bethesda, MD [U10 CA98543, U10 CA98413] FX Supported by Chair Grant No. U10 CA98543 and Statistics and Data Center Grant No. U10 CA98413 from the Children's Oncology Group, National Cancer Institute, National Institutes of Health, Bethesda, MD. NR 54 TC 5 Z9 5 U1 0 U2 9 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 20 PY 2012 VL 30 IS 36 BP 4573 EP 4579 DI 10.1200/JCO.2012.45.2086 PG 7 WC Oncology SC Oncology GA 060YT UT WOS:000312815000025 PM 23109703 ER PT J AU Guo, SZ Zhou, YM Xing, CH Lok, J Som, AT Ning, MM Ji, XM Lo, EH AF Guo, Shuzhen Zhou, Yiming Xing, Changhong Lok, Josephine Som, Angel T. Ning, MingMing Ji, Xunming Lo, Eng H. TI The Vasculome of the Mouse Brain SO PLOS ONE LA English DT Article ID CEREBRAL ENDOTHELIAL-CELLS; UCH37 DEUBIQUITINATING ENZYME; SPINOCEREBELLAR ATAXIA TYPE-1; PSORIASIS SUSCEPTIBILITY GENE; ENDOPLASMIC-RETICULUM STRESS; CHROMATIN-REMODELING COMPLEX; LONG-TERM POTENTIATION; NITRIC-OXIDE SYNTHASE; 20-LIKE KINASE-3 MST3; C FAMILY-MEMBERS AB The blood vessel is no longer viewed as passive plumbing for the brain. Increasingly, experimental and clinical findings suggest that cerebral endothelium may possess endocrine and paracrine properties - actively releasing signals into and receiving signals from the neuronal parenchyma. Hence, metabolically perturbed microvessels may contribute to central nervous system (CNS) injury and disease. Furthermore, cerebral endothelium can serve as sensors and integrators of CNS dysfunction, releasing measurable biomarkers into the circulating bloodstream. Here, we define and analyze the concept of a brain vasculome, i.e. a database of gene expression patterns in cerebral endothelium that can be linked to other databases and systems of CNS mediators and markers. Endothelial cells were purified from mouse brain, heart and kidney glomeruli. Total RNA were extracted and profiled on Affymetrix mouse 430 2.0 micro-arrays. Gene expression analysis confirmed that these brain, heart and glomerular preparations were not contaminated by brain cells (astrocytes, oligodendrocytes, or neurons), cardiomyocytes or kidney tubular cells respectively. Comparison of the vasculome between brain, heart and kidney glomeruli showed that endothelial gene expression patterns were highly organ-dependent. Analysis of the brain vasculome demonstrated that many functionally active networks were present, including cell adhesion, transporter activity, plasma membrane, leukocyte transmigration, Wnt signaling pathways and angiogenesis. Analysis of representative genome-wide-association-studies showed that genes linked with Alzheimer's disease, Parkinson's disease and stroke were detected in the brain vasculome. Finally, comparison of our mouse brain vasculome with representative plasma protein databases demonstrated significant overlap, suggesting that the vasculome may be an important source of circulating signals in blood. Perturbations in cerebral endothelial function may profoundly affect CNS homeostasis. Mapping and dissecting the vasculome of the brain in health and disease may provide a novel database for investigating disease mechanisms, assessing therapeutic targets and exploring new biomarkers for the CNS. C1 [Guo, Shuzhen; Zhou, Yiming; Xing, Changhong; Lok, Josephine; Som, Angel T.; Ning, MingMing; Lo, Eng H.] Harvard Univ, Sch Med, Dept Radiol, Neuroprotect Res Lab,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Guo, Shuzhen; Zhou, Yiming; Xing, Changhong; Lok, Josephine; Som, Angel T.; Ning, MingMing; Lo, Eng H.] Harvard Univ, Sch Med, Dept Neurol, Neuroprotect Res Lab,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Zhou, Yiming] Broad Inst Massachusetts Inst Technol & Harvard M, Boston, MA USA. [Lok, Josephine] Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Ning, MingMing; Lo, Eng H.] Harvard Univ, Sch Med, Dept Neurol, Clin Prote Res Ctr,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Ji, Xunming] Capital Med Univ, Cerebrovasc Res Ctr, XuanWu Hosp, Beijing, Peoples R China. RP Guo, SZ (reprint author), Harvard Univ, Sch Med, Dept Radiol, Neuroprotect Res Lab,Massachusetts Gen Hosp, Boston, MA 02115 USA. EM sguo@partners.org; Lo@helix.mgh.harvard.edu FU NIH [RC2-NS69335, R37-NS37074, R01-NS76694, P01-NS55104]; Claflin award from Massachusetts General Hospital; Phyliss and Jerome Lyle Rappaport MGH Research Scholar award; Beijing Natural Science Foundation; China National Basic Research 973 Program FX This study was supported by studies funded in part by grants from the NIH (RC2-NS69335, R37-NS37074, R01-NS76694, P01-NS55104), the Claflin award from Massachusetts General Hospital, the Phyliss and Jerome Lyle Rappaport MGH Research Scholar award, the Beijing Natural Science Foundation, and the China National Basic Research 973 Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 208 TC 14 Z9 14 U1 0 U2 16 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 20 PY 2012 VL 7 IS 12 AR e52665 DI 10.1371/journal.pone.0052665 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 060RA UT WOS:000312794500225 PM 23285140 ER PT J AU Rottman, M Goldberg, J Hacking, SA AF Rottman, Martin Goldberg, Joel Hacking, S. Adam TI Titanium-Tethered Vancomycin Prevents Resistance to Rifampicin in Staphylococcus aureus in vitro SO PLOS ONE LA English DT Article ID CLINICAL-PRACTICE; BIOFILM FORMATION; ALLOY; SURFACE; ATTACHMENT; INFECTION; INHIBITION; KNEE; COLONIZATION; ANTIBIOTICS AB Rifampicin is currently recognized as the most potent drug against Gram positive implant related infections. The use of rifampicin is limited by the emergence of bacterial resistance, which is often managed by coadministration of a second antibiotic. The purpose of this study was to determine the effectiveness of soluble rifampicin in combination with vancomycin tethered to titanium metal as a means to control bacterial growth and resistance in vitro. Bacterial growth was inhibited when the vancomycin-tethered titanium discs were treated with Staphylococcus aureus inocula of >= 2 x 10(6) CFU, however inocula greater than 2 x 10(6) CFU/disc adhered and survived. The combination of surface-tethered vancomycin with soluble rifampicin enhanced the inhibitory effect of rifampicin for an inoculum of 10(6) CFU/cm(2) by one dilution (combination MIC of 0.008 mg/L versus 0.015 mg/L for rifampicin alone). Moreover, surface tethered vancomycin prevented the emergence of a rifampicin resistant population in an inoculum of 2 x 10(8) CFU. Citation: Rottman M, Goldberg J, Hacking SA (2012) Titanium-Tethered Vancomycin Prevents Resistance to Rifampicin in Staphylococcus aureus in vitro. PLoS ONE 7(12): e52883. doi: 10.1371/journal.pone.0052883 C1 [Rottman, Martin; Goldberg, Joel; Hacking, S. Adam] Harvard Univ, Sch Med, Lab Musculoskeletal Res & Innovat, Dept Orthopaed, Boston, MA 02114 USA. [Rottman, Martin; Goldberg, Joel; Hacking, S. Adam] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rottman, Martin] Harvard Univ, Sch Med, Wyss Inst, Boston, MA USA. [Rottman, Martin] Univ Versailles St Quentin, EA Physiopathol & Diagnost Infect Microbiennes 36, Garches, France. [Rottman, Martin] Hop Raymond Poincare, AP HP, Microbiol Lab, Garches, France. RP Hacking, SA (reprint author), Harvard Univ, Sch Med, Lab Musculoskeletal Res & Innovat, Dept Orthopaed, Boston, MA 02114 USA. EM ahacking@partners.org RI Rottman, Martin/I-3005-2012 OI Rottman, Martin/0000-0001-5953-3344 NR 32 TC 5 Z9 5 U1 0 U2 17 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 20 PY 2012 VL 7 IS 12 AR e52883 DI 10.1371/journal.pone.0052883 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 060RA UT WOS:000312794500253 PM 23285213 ER PT J AU Nejad, SH Schaefer, PW Bajwa, EK Smith, FA AF Nejad, Shamim H. Schaefer, Pamela W. Bajwa, Ednan K. Smith, Felicia A. TI Case 39-2012: A 55-Year-Old Man with Alcoholism, Recurrent Seizures, and Agitation Delirium (alcohol withdrawal delirium and multifactorial delirium). SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SYNDROME PRACTICE GUIDELINE C1 [Nejad, Shamim H.; Smith, Felicia A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Schaefer, Pamela W.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Bajwa, Ednan K.] Massachusetts Gen Hosp, Dept Pulm & Crit Care, Boston, MA 02114 USA. [Nejad, Shamim H.; Smith, Felicia A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Schaefer, Pamela W.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Bajwa, Ednan K.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Nejad, SH (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 11 TC 0 Z9 0 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 20 PY 2012 VL 367 IS 25 BP 2428 EP 2434 DI 10.1056/NEJMcpc1114035 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 056ZP UT WOS:000312531600012 PM 23252529 ER PT J AU Yamaguchi, S Hong, K Liu, R Shen, L Inoue, A Diep, D Zhang, K Zhang, Y AF Yamaguchi, Shinpei Hong, Kwonho Liu, Rui Shen, Li Inoue, Azusa Diep, Dinh Zhang, Kun Zhang, Yi TI Tet1 controls meiosis by regulating meiotic gene expression SO NATURE LA English DT Article ID PRIMORDIAL GERM-CELLS; DNA METHYLATION; EPIGENETIC EVENTS; MAMMALIAN DNA; MOUSE; MICE; 5-CARBOXYLCYTOSINE; 5-METHYLCYTOSINE; SPECIFICATION; PLURIPOTENCY AB Meiosis is a germ-cell-specific cell division process through which haploid gametes are produced for sexual reproduction(1). Before the initiation of meiosis, mouse primordial germ cells undergo a series of epigenetic reprogramming steps(2,3), including the global erasure of DNA methylation at the 5-position of cytosine (5mC) in CpG-rich DNA(4,5). Although several epigenetic regulators, such as Dnmt3l and the histone methyltransferases G9a and Prdm9, have been reported to be crucial for meiosis(6), little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. Using a loss-of-function approach in mice, here we show that the 5mC-specific dioxygenase Tet1 has an important role in regulating meiosis in mouse oocytes. Tet1 deficiency significantly reduces female germ-cell numbers and fertility. Univalent chromosomes and unresolved DNA double-strand breaks are also observed in Tet1-deficient oocytes. Tet1 deficiency does not greatly affect the genome-wide demethylation that takes place in primordial germ cells, but leads to defective DNA demethylation and decreased expression of a subset of meiotic genes. Our study thus establishes a function for Tet1 in meiosis and meiotic gene activation in female germ cells. C1 [Liu, Rui; Diep, Dinh; Zhang, Kun] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. [Yamaguchi, Shinpei; Hong, Kwonho; Shen, Li; Inoue, Azusa; Zhang, Yi] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Yamaguchi, Shinpei; Hong, Kwonho; Shen, Li; Inoue, Azusa; Zhang, Yi] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Yamaguchi, Shinpei; Hong, Kwonho; Shen, Li; Inoue, Azusa; Zhang, Yi] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Zhang, Yi] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Zhang, K (reprint author), Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. EM kzhang@bioeng.ucsd.edu; yzhang@genetics.med.harvard.edu OI Yamaguchi, Shinpei/0000-0002-9377-4835 FU National Institutes of Health [U01DK089565]; CIRM [BRB3-05083]; [R01GM097253] FX We thank J. Wang and W. Jiang for FACS sorting, A. Adey and J. Shendure for sharing reagents and protocols for Tn5mC-seq, and H.-L. Fung for Illumina sequencing. This work was partially supported by U01DK089565 (National Institutes of Health) (to Y.Z.), R01GM097253 and CIRM BRB3-05083 (to K.Z.). Y.Z. is an Investigator of the Howard Hughes Medical Institute. D.D. is a CIRM-UCSD pre-doctoral fellow. NR 29 TC 98 Z9 100 U1 2 U2 60 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 20 PY 2012 VL 492 IS 7429 BP 443 EP + DI 10.1038/nature11709 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 056KQ UT WOS:000312488200059 PM 23151479 ER PT J AU Zielinski, D Gymrek, M Erlich, Y AF Zielinski, Dina Gymrek, Melissa Erlich, Yaniv TI Back to the family: a renewed approach to rare variant studies SO GENOME MEDICINE LA English DT Editorial Material AB A report on the 62nd Annual Meeting of the American Society of Human Genetics, San Francisco, California, USA, 6-10 November 2012. C1 [Zielinski, Dina; Gymrek, Melissa; Erlich, Yaniv] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Gymrek, Melissa] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Gymrek, Melissa] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Gymrek, Melissa] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Gymrek, Melissa] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. RP Erlich, Y (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM yaniv@wi.mit.edu OI /0000-0002-6086-3903 NR 0 TC 1 Z9 2 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PD DEC 19 PY 2012 VL 4 AR 97 DI 10.1186/gm398 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 084ZM UT WOS:000314580400001 PM 23253160 ER PT J AU Liu, CY Maity, A Lin, XH Wright, RO Christiani, DC AF Liu, Chen-yu Maity, Arnab Lin, Xihong Wright, Robert O. Christiani, David C. TI Design and analysis issues in gene and environment studies SO ENVIRONMENTAL HEALTH LA English DT Review DE Gene-environment; Interactions; Expanded environmental genomic disease paradigm; Critical developmental windows; Genome-wide; Epigenetics ID GENOME-WIDE ASSOCIATION; PROSTATE-SPECIFIC ANTIGEN; MULTIVARIATE ADAPTIVE SPLINES; VARYING COEFFICIENT MODELS; SAMPLE-SIZE REQUIREMENTS; COMPLEX HUMAN-DISEASES; CASE-ONLY DESIGNS; POPULATION STRATIFICATION; NONDIFFERENTIAL MISCLASSIFICATION; MOLECULAR EPIDEMIOLOGY AB Both nurture (environmental) and nature (genetic factors) play an important role in human disease etiology. Traditionally, these effects have been thought of as independent. This perspective is ill informed for non-mendelian complex disorders which result as an interaction between genetics and environment. To understand health and disease we must study how nature and nurture interact. Recent advances in human genomics and high-throughput biotechnology make it possible to study large numbers of genetic markers and gene products simultaneously to explore their interactions with environment. The purpose of this review is to discuss design and analytic issues for gene-environment interaction studies in the "-omics" era, with a focus on environmental and genetic epidemiological studies. We present an expanded environmental genomic disease paradigm. We discuss several study design issues for gene-environmental interaction studies, including confounding and selection bias, measurement of exposures and genotypes. We discuss statistical issues in studying gene-environment interactions in different study designs, such as choices of statistical models, assumptions regarding biological factors, and power and sample size considerations, especially in genome-wide gene-environment studies. Future research directions are also discussed. C1 [Liu, Chen-yu; Wright, Robert O.; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA. [Liu, Chen-yu] Natl Taiwan Univ, Coll Publ Hlth, Inst Environm Hlth, Taipei 10764, Taiwan. [Maity, Arnab; Lin, Xihong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Maity, Arnab] N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA. [Wright, Robert O.] Mt Sinai Sch Med, Dept Prevent Med, New York, NY USA. [Christiani, David C.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu RI MAITY, ARNAB/M-8142-2016; OI MAITY, ARNAB/0000-0002-3364-8933; LIU, CHEN-YU/0000-0002-4693-5667 FU [ES P42 016454]; [5R37CA076404]; [5P01CA134294]; [R00ES017744] FX Supported in part by ES P42 016454, 5R37CA076404, 5P01CA134294, R00ES017744. NR 121 TC 9 Z9 10 U1 1 U2 34 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-069X J9 ENVIRON HEALTH-GLOB JI Environ. Health PD DEC 19 PY 2012 VL 11 AR 93 DI 10.1186/1476-069X-11-93 PG 15 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 084WV UT WOS:000314571800001 PM 23253229 ER PT J AU Harati, R Villegier, AS Banks, WA Mabondzo, A AF Harati, Rania Villegier, Anne-Sophie Banks, William A. Mabondzo, Aloise TI Susceptibility of juvenile and adult blood-brain barrier to endothelin-1: regulation of P-glycoprotein and breast cancer resistance protein expression and transport activity SO JOURNAL OF NEUROINFLAMMATION LA English DT Article DE Juvenile and adult blood-brain barrier; Neuroinflammation; Endothelin-1; Brain-to-blood transport; Drug transport; P-glycoprotein; Breast cancer resistance protein ID NECROSIS-FACTOR-ALPHA; DRUG EFFLUX TRANSPORTERS; IN-VITRO MODEL; TRANSCRIPTIONAL REGULATION; CEREBROSPINAL-FLUID; RAT ASTROCYTES; MICROGLIA; DISEASES; INFLAMMATION; SYSTEM AB Background: P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) play a critical role in keeping neurotoxic substances from entering the brain. We and others have previously reported an impact of inflammation on the regulation of adult blood-brain barrier (BBB) efflux transporters. However, studies in children have not been done. From the pediatric clinical perspective, it is important to understand how the central nervous system (CNS) and BBB drug efflux transporters differ in childhood from those of adults under normal and inflammatory conditions. Therefore, we examined and compared the regulation of P-gp and BCRP expression and transport activity in young and adult BBB and investigated the molecular mechanisms underlying inflammatory responses. Methods: Rats at postnatal day (P) P21 and P84, corresponding to the juvenile and adult stages of human brain maturation, respectively, were treated with endothelin-1 (ET-1) given by the intracerebroventricular (icv) route. Twenty-four hours later, we measured P-gp and BCRP protein expression in isolated brain capillary by immunoblotting as well as by transport activity in vivo by measuring the unbound drug partitioning coefficient of the brain (K-p,K-uu,K-brain) of known efflux transporter substrates administered intravenously. Glial activation was measured by immunohistochemistry. The release of cytokines/chemokines (interleukins-1 alpha, 1-beta (IL-1 beta), -6 (IL-6), -10 (IL-10), monocyte chemoattractant protein (MCP-1/CCL2), fractalkine and tissue inhibitor of metalloproteinases-1 (TIMP-1)) were simultaneously measured in brain and serum samples using the Agilent Technology cytokine microarray. Results: We found that juvenile and adult BBBs exhibited similar P-gp and BCRP transport activities in the normal physiological conditions. However, long-term exposure of the juvenile brain to low-dose of ET-1 did not change BBB P-gp transport activity but tended to decrease BCRP transport activity in the juvenile brain, while a significant increase of the activity of both transporters was evidenced at the BBB in the adult brain. Moreover, juvenile and adult brain showed differences in their expression profiles of cytokines and chemokines mediated by ET-1. Conclusions: BBB transporter activity during neuroinflammation differs between the juvenile and adult brains. These findings emphasize the importance of considering differential P-gp and BCRP transport regulation mechanisms between adult and juvenile BBB in the context of neuroinflammation. C1 [Harati, Rania; Mabondzo, Aloise] CEA, Direct Sci Vivant, iBiTec S, Serv Pharmacol & Immunoanal, F-91191 Gif Sur Yvette, France. [Villegier, Anne-Sophie] Inst Natl Environm Ind & Risques INERIS, Dept Expt Toxicol, F-60550 Verneuil En Halatte, France. [Banks, William A.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, GRECC,Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Mabondzo, A (reprint author), CEA, Direct Sci Vivant, iBiTec S, Serv Pharmacol & Immunoanal, F-91191 Gif Sur Yvette, France. EM aloise.mabondzo@cea.fr FU Agence National de Recherche sur le SIDA FX We would like to thank the Agence National de Recherche sur le SIDA for financial support. The authors thank Aurelie Ghettas (CEA, iBiTec-S, Service de Pharmacologie et d'Immunoanalyse, Gif-sur-Yvette, France) and Kelly Blazy (INERIS, 60550 Verneuil-en-Halatte, France) for their technical skills in mass spectrometry and immunohistochemical techniques, respectively. NR 63 TC 4 Z9 6 U1 0 U2 17 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-2094 J9 J NEUROINFLAMM JI J. Neuroinflamm. PD DEC 19 PY 2012 VL 9 AR 273 DI 10.1186/1742-2094-9-273 PG 16 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 087ID UT WOS:000314753900002 PM 23253775 ER PT J AU Teng, YD Benn, SC Kalkanis, SN Shefner, JM Onario, RC Cheng, B Lachyankar, MB Marconi, M Li, JX Yu, D Han, IB Maragakis, NJ Llado, J Erkmen, K Redmond, DE Sidman, RL Przedborski, S Rothstein, JD Brown, RH Snyder, EY AF Teng, Yang D. Benn, Susanna C. Kalkanis, Steven N. Shefner, Jeremy M. Onario, Renna C. Cheng, Bin Lachyankar, Mahesh B. Marconi, Michael Li, Jianxue Yu, Dou Han, Inbo Maragakis, Nicholas J. Llado, Jeronia Erkmen, Kadir Redmond, D. Eugene, Jr. Sidman, Richard L. Przedborski, Serge Rothstein, Jeffrey D. Brown, Robert H., Jr. Snyder, Evan Y. TI Multimodal Actions of Neural Stem Cells in a Mouse Model of ALS: A Meta-Analysis SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; CU/ZN SUPEROXIDE-DISMUTASE; SPINAL-CORD-INJURY; TRANSGENIC RAT MODEL; MOTOR-NEURONS; MUTANT SOD1; DISEASE PROGRESSION; NEUROTROPHIC FACTOR; FAMILIAL ALS; PROGENITOR CELLS AB Amyotrophic lateral sclerosis (ALS) is a lethal disease characterized by the unremitting degeneration of motor neurons. Multiple processes involving motor neurons and other cell types have been implicated in its pathogenesis. Neural stem cells (NSCs) perform multiple actions within the nervous system to fulfill their functions of organogenesis and homeostasis. We test the hypothesis that transplanted, undifferentiated multipotent migratory NSCs may help to ameliorate an array of pathological mechanisms in the SOD1(G93A) transgenic mouse model of ALS. On the basis of a meta-analysis of 11 independent studies performed by a consortium of ALS investigators, we propose that transplanted NSCs (both mouse and human) can slow both the onset and the progression of clinical signs and prolong survival in ALS mice, particularly if regions sustaining vital functions such as respiration are rendered chimeric. The beneficial effects of transplanted NSCs seem to be mediated by a number of actions including their ability to produce trophic factors, preserve neuromuscular function, and reduce astrogliosis and inflammation. We conclude that the widespread, pleiotropic, modulatory actions exerted by transplanted NSCs may represent an accessible therapeutic application of stem cells for treating ALS and other untreatable degenerative diseases. C1 [Teng, Yang D.; Kalkanis, Steven N.; Onario, Renna C.; Yu, Dou; Han, Inbo; Erkmen, Kadir; Sidman, Richard L.; Snyder, Evan Y.] Spaulding Rehabil Hosp, Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Teng, Yang D.; Kalkanis, Steven N.; Onario, Renna C.; Yu, Dou; Han, Inbo; Erkmen, Kadir; Sidman, Richard L.; Snyder, Evan Y.] Spaulding Rehabil Hosp, Brigham & Womens Hosp, Dept PM&R, Boston, MA 02115 USA. [Teng, Yang D.; Onario, Renna C.; Yu, Dou; Han, Inbo] Vet Affairs Boston Healthcare Syst, SCI Res, Boston, MA 02132 USA. [Teng, Yang D.; Onario, Renna C.; Lachyankar, Mahesh B.; Marconi, Michael; Erkmen, Kadir; Snyder, Evan Y.] Harvard Univ, Sch Med, Dept Neurol, Boston Childrens Hosp, Boston, MA 02115 USA. [Teng, Yang D.; Kalkanis, Steven N.; Onario, Renna C.; Yu, Dou; Han, Inbo; Erkmen, Kadir; Sidman, Richard L.; Snyder, Evan Y.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Benn, Susanna C.; Kalkanis, Steven N.; Brown, Robert H., Jr.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shefner, Jeremy M.] SUNY Syracuse, Dept Neurol, Syracuse, NY 13210 USA. [Cheng, Bin] Columbia Univ, Dept Biostat, Mailman Sch Publ Hlth, New York, NY 10032 USA. [Marconi, Michael; Li, Jianxue; Sidman, Richard L.; Snyder, Evan Y.] Harvard Univ, Sch Med, Dept Neurol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Maragakis, Nicholas J.; Llado, Jeronia; Rothstein, Jeffrey D.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21287 USA. [Redmond, D. Eugene, Jr.] Yale Univ, Sch Med, Dept Psychiat & Neurosurg, New Haven, CT 06520 USA. [Przedborski, Serge] Columbia Univ, Coll Phys & Surg, Neurol Inst, Movement Disorder Div,Ctr Neurobiol & Behav, New York, NY 10032 USA. [Brown, Robert H., Jr.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01655 USA. [Snyder, Evan Y.] Sanford Burnham Med Res Inst, La Jolla, CA 92037 USA. RP Teng, YD (reprint author), Spaulding Rehabil Hosp, Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. EM yang_teng@hms.harvard.edu; Robert.Brown@umassmed.edu; esnyder@sanfordburnham.org RI rothstein, jeffrey/C-9470-2013 FU Project ALS; California Institute for Regenerative Medicine (CIRM); National Institute of Neurological Disorders and Stroke (NINDS) [RO1-NS34247, R21NS053935]; VA Biomedical Research and Development Grant [VA B2958]; VA Rehabilitation Research and Development Grant [B7076R]; Christopher Reeve Foundation/American Paralysis Association; Sanford Children's Research Center; A-T Children's Project; Zinberg Foundation; ALS Therapy Alliance; ALS Association; Angel Fund; Al-Athel Foundation; Pierre L. deBourgknect ALS Research Foundation; P2ALS; NINDS [1RC2NS070342-01, 1RC1NS068391-01, R01NS050557-05, U01NS05225-03] FX This work was supported by Project ALS, California Institute for Regenerative Medicine (CIRM), National Institute of Neurological Disorders and Stroke (NINDS) (RO1-NS34247 to E.Y.S. and R21NS053935 to Y.D.T.), VA Biomedical Research and Development Grant (VA B2958 O to Y.D.T.), VA Rehabilitation Research and Development Grant (Project B7076R to Y.D.T.), the Christopher Reeve Foundation/American Paralysis Association, Sanford Children's Research Center, A-T Children's Project, and the Zinberg Foundation. R. H. B. is also supported by the ALS Therapy Alliance, the ALS Association, the Angel Fund, the Al-Athel Foundation, the Pierre L. deBourgknect ALS Research Foundation, P2ALS, and NINDS awards 1RC2NS070342-01, 1RC1NS068391-01, R01NS050557-05, and U01NS05225-03. NR 109 TC 35 Z9 35 U1 3 U2 20 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD DEC 19 PY 2012 VL 4 IS 165 AR 165ra164 DI 10.1126/scitranslmed.3004579 PG 14 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 059WR UT WOS:000312736700004 PM 23253611 ER PT J AU Monson, CM Resick, PA Schnurr, PP AF Monson, Candice M. Resick, Patricia A. Schnurr, Paula P. TI Couple Therapy for Posttraumatic Stress Disorder Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID PSYCHOTHERAPY OUTCOME RESEARCH C1 [Monson, Candice M.] Ryerson Univ, Toronto, ON, Canada. [Resick, Patricia A.] VA Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Schnurr, Paula P.] VA Natl Ctr PTSD, Execut Div, White River Jct, VT USA. RP Monson, CM (reprint author), Ryerson Univ, Toronto, ON, Canada. EM candice.monson@psych.ryerson.ca NR 3 TC 0 Z9 0 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 19 PY 2012 VL 308 IS 23 BP 2458 EP 2458 DI 10.1001/jama.2012.14573 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 055TU UT WOS:000312441400016 ER PT J AU Gregg, EW Chen, HY Wagenknecht, LE Clark, JM Delahanty, LM Bantle, J Pownall, HJ Johnson, KC Safford, MM Kitabchi, AE Pi-Sunyer, FX Wing, RR Bertoni, AG AF Gregg, Edward W. Chen, Haiying Wagenknecht, Lynne E. Clark, Jeanne M. Delahanty, Linda M. Bantle, John Pownall, Henry J. Johnson, Karen C. Safford, Monika M. Kitabchi, Abbas E. Pi-Sunyer, F. Xavier Wing, Rena R. Bertoni, Alain G. CA Look AHEAD Res Grp TI Association of an Intensive Lifestyle Intervention With Remission of Type 2 Diabetes SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; BARIATRIC SURGERY; PREVENTION PROGRAM; GLUCOSE-TOLERANCE; MEDICAL THERAPY; OBESE-PATIENTS; WEIGHT-LOSS; MELLITUS; REDUCTION; OUTCOMES AB Context The frequency of remission of type 2 diabetes achievable with lifestyle intervention is unclear. Objective To examine the association of a long-term intensive weight-loss intervention with the frequency of remission from type 2 diabetes to prediabetes or normoglycemia. Design, Setting, and Participants Ancillary observational analysis of a 4-year randomized controlled trial (baseline visit, August 2001-April 2004; last follow-up, April 2008) comparing an intensive lifestyle intervention (ILI) with a diabetes support and education control condition (DSE) among 4503 US adults with body mass index of 25 or higher and type 2 diabetes. Interventions Participants were randomly assigned to receive the ILI, which included weekly group and individual counseling in the first 6 months followed by 3 sessions per month for the second 6 months and twice-monthly contact and regular refresher group series and campaigns in years 2 to 4 (n=2241) or the DSE, which was an offer of 3 group sessions per year on diet, physical activity, and social support (n=2262). Main Outcome Measures Partial or complete remission of diabetes, defined as transition from meeting diabetes criteria to a prediabetes or nondiabetic level of glycemia (fasting plasma glucose <126 mg/dL and hemoglobin A(1c) <6.5% with no antihyperglycemic medication). Results Intensive lifestyle intervention participants lost significantly more weight than DSE participants at year 1 (net difference, -7.9%; 95% CI, -8.3% to -7.6%) and at year 4 (-3.9%; 95% CI, -4.4% to -3.5%) and had greater fitness increases at year 1 (net difference, 15.4%; 95% CI, 13.7%-17.0%) and at year 4 (6.4%; 95% CI, 4.7%-8.1%) (P<.001 for each). The ILI group was significantly more likely to experience any remission (partial or complete), with prevalences of 11.5% (95% CI, 10.1%-12.8%) during the first year and 7.3% (95% CI, 6.2%-8.4%) at year 4, compared with 2.0% for the DSE group at both time points (95% CIs, 1.4%-2.6% at year 1 and 1.5%-2.7% at year 4) (P<.001 for each). Among ILI participants, 9.2% (95% CI, 7.9%-10.4%), 6.4% (95% CI, 5.3%-7.4%), and 3.5% (95% CI, 2.7%-4.3%) had continuous, sustained remission for at least 2, at least 3, and 4 years, respectively, compared with less than 2% of DSE participants (1.7% [95% CI, 1.2%-2.3%] for at least 2 years; 1.3% [95% CI, 0.8%-1.7%] for at least 3 years; and 0.5% [95% CI, 0.2%-0.8%] for 4 years). Conclusions In these exploratory analyses of overweight adults, an intensive lifestyle intervention was associated with a greater likelihood of partial remission of type 2 diabetes compared with diabetes support and education. However, the absolute remission rates were modest. C1 [Gregg, Edward W.] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA 30341 USA. [Chen, Haiying; Wagenknecht, Lynne E.; Bertoni, Alain G.] Wake Forest Sch Med, Winston Salem, NC USA. [Clark, Jeanne M.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Delahanty, Linda M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bantle, John] Univ Minnesota, Minneapolis, MN USA. [Pownall, Henry J.] Baylor Coll Med, Houston, TX 77030 USA. [Johnson, Karen C.; Kitabchi, Abbas E.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Safford, Monika M.] Univ Alabama Birmingham, Birmingham, AL USA. [Pi-Sunyer, F. Xavier] Columbia Univ, St Lukes Roosevelt Hosp, New York, NY USA. [Wing, Rena R.] Miriam Hosp, Brown Med Sch, Providence, RI 02906 USA. RP Gregg, EW (reprint author), Ctr Dis Control & Prevent, Div Diabet Translat, 4770 Buford Hwy NE,MS K-10, Atlanta, GA 30341 USA. EM edg7@cdc.gov FU US Department of Health and Human Services from the National Institutes of Health (NIH) [DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, DK56992]; National Institute of Diabetes and Digestive and Kidney Diseases; 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. The Indian Health Service (IHS); 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 Clinical 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 [M01RR000056]; Clinical Translational Research Center; Clinical and Translational Science Award [UL1 RR 024153]; NIH [DK 046204]; VA Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs; Frederic C. Bartter General Clinical Research Center [M01RR01346] FX This study is supported by the US Department of Health and Human Services through the following cooperative agreements from the National Institutes of Health (NIH): DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, and DK56992. The following federal agencies have contributed support: National Institute of Diabetes and Digestive and Kidney Diseases; 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 (IHS) provided personnel, medical oversight, and use of facilities. 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 Clinical 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 (M01RR000056), the Clinical Translational Research Center funded by 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). The following organizations have committed to making major contributions to Look AHEAD: FedEx Corp; Health Management Resources; LifeScan Inc, a Johnson and Johnson Company; OPTIFAST of Nestle HealthCare Nutrition Inc; Hoffmann-La Roche Inc; Abbott Nutrition; and Slim-Fast Brand of Unilever North America. NR 32 TC 157 Z9 162 U1 2 U2 59 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 19 PY 2012 VL 308 IS 23 BP 2489 EP 2496 DI 10.1001/jama.2012.67929 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 055TU UT WOS:000312441400025 PM 23288372 ER PT J AU Esipova, TV Ye, XC Collins, JE Sakadzic, S Mandeville, ET Murray, CB Vinogradov, SA AF Esipova, Tatiana V. Ye, Xingchen Collins, Joshua E. Sakadzic, Sava Mandeville, Emiri T. Murray, Christopher B. Vinogradov, Sergei A. TI Dendritic upconverting nanoparticles enable in vivo multiphoton microscopy with low-power continuous wave sources SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID UP-CONVERSION FLUORESCENCE; LANTHANIDE-DOPED NANOCRYSTALS; NAYF4 NANOCRYSTALS; NANOPHOSPHORS; DENDRIMERS; LUMINESCENCE; LASER; PORPHYRIN; EMISSION; CELLS AB We report a group of optical imaging probes, comprising upconverting lanthanide nanoparticles (UCNPs) and polyanionic dendrimers. Dendrimers with rigid cores and multiple carboxylate groups at the periphery are able to tightly bind to surfaces of UCNPs pretreated with NOBF4, yielding stable, water-soluble, biocompatible nanomaterials. Unlike conventional linear polymers, dendrimers adhere to UCNPs by donating only a fraction of their peripheral groups to the UCNP-surface interactions. The remaining termini make up an interface between the nanoparticle and the aqueous phase, enhancing solubility and offering multiple possibilities for subsequent modification. Using optical probes as dendrimer cores makes it possible to couple the UCNPs signal to analyte-sensitive detection via UCNP-to-chromophore excitation energy transfer (EET). As an example, we demonstrate that UCNPs modified with porphyrin-dendrimers can operate as upconverting ratiometric pH nanosensors. Dendritic UCNPs possess excellent photostability, solubility, and biocompatibility, which make them directly suitable for in vivo imaging. Polyglutamic dendritic UCNPs injected in the blood of a mouse allowed mapping of the cortical vasculature down to 400 mu m under the tissue surface, thus demonstrating feasibility of in vivo high-resolution two-photon microscopy with continuous wave (CW) excitation sources. Dendrimerization as a method of solubilization of UCNPs opens up numerous possibilities for use of these unique agents in biological imaging and sensing. C1 [Esipova, Tatiana V.; Vinogradov, Sergei A.] Univ Penn, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. [Ye, Xingchen; Murray, Christopher B.] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. [Murray, Christopher B.] Univ Penn, Dept Mat Sci, Philadelphia, PA 19104 USA. [Collins, Joshua E.] Intelligent Mat Solut Inc, Princeton, NJ 08540 USA. [Sakadzic, Sava] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Opt Div,Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Mandeville, Emiri T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab, Charlestown, MA 02129 USA. [Mandeville, Emiri T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Charlestown, MA 02129 USA. [Mandeville, Emiri T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Charlestown, MA 02129 USA. RP Murray, CB (reprint author), Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. EM cbmurray@sas.upenn.edu; vinograd@mail.med.upenn.edu RI Ye, Xingchen/D-3202-2017 OI Ye, Xingchen/0000-0001-6851-2721 FU Nano/Bio Interface Center through National Science Foundation Nanoscale Science and Engineering Centers [DMR08-32802]; Penn Medicine Neuroscience Center; Office of Naval Research Multidisciplinary University Research Initiative on Optical Metamaterials [N00014-10-1-0942]; American Heart Association [11SDG7600037]; National Institutes of Health [S10-RR022428] FX This work was supported, in part, by the Nano/Bio Interface Center through National Science Foundation Nanoscale Science and Engineering Centers Grant DMR08-32802 (to S. A. V. and C. B. M.), the Penn Medicine Neuroscience Center grant (to S. A. V.), the Office of Naval Research Multidisciplinary University Research Initiative on Optical Metamaterials through Award N00014-10-1-0942 (to C. B. M.), American Heart Association Grant 11SDG7600037 (to S. S.), and Prairie Microscope Shared Instrument Equipment Grant S10-RR022428 from the National Institutes of Health. NR 55 TC 42 Z9 42 U1 12 U2 113 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 18 PY 2012 VL 109 IS 51 BP 20826 EP 20831 DI 10.1073/pnas.1213291110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 065BZ UT WOS:000313123700024 PM 23213211 ER PT J AU Li, S Chakraborty, N Borcar, A Menze, MA Toner, M Hand, SC AF Li, Shumin Chakraborty, Nilay Borcar, Apurva Menze, Michael A. Toner, Mehmet Hand, Steven C. TI Late embryogenesis abundant proteins protect human hepatoma cells during acute desiccation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE water stress; biopreservation; intrinsically disordered proteins; osmolyte; Artemia franciscana ID MAMMALIAN-CELLS; WATER-STRESS; ARTEMIA-FRANCISCANA; ENCYSTED EMBRYOS; LEA PROTEINS; TREHALOSE; TOLERANCE; ANHYDROBIOSIS; MITOCHONDRIA; DEHYDRATION AB Expression of late embryogenesis abundant (LEA) proteins is highly correlated with desiccation tolerance in anhydrobiotic animals, selected land plants, and bacteria. Genes encoding two LEA proteins, one localized to the cytoplasm/nucleus (AfrLEA2) and one targeted to mitochondria (AfrLEA3m), were stably transfected into human HepG2 cells. A trehalose transporter was used for intracellular loading of this disaccharide. Cells were rapidly and uniformly desiccated to low water content (<0.12 g H2O/g dry weight) with a recently developed spin-drying technique. Immediately on rehydration, control cells without LEA proteins or trehalose exhibited 0% membrane integrity, compared with 98% in cells loaded with trehalose and expressing AfrLEA2 or AfrLEA3m; surprisingly, AfrLEA3m without trehalose conferred 94% protection. Cell proliferation across 7 d showed an 18-fold increase for cells dried with AfrLEA3m and trehalose, compared with 27-fold for nondried controls. LEA proteins dramatically enhance desiccation tolerance in mammalian cells and offer the opportunity for engineering biostability in the dried state. C1 [Li, Shumin; Borcar, Apurva; Hand, Steven C.] Louisiana State Univ, Dept Biol Sci, Div Cellular Dev & Integrat Biol, Baton Rouge, LA 70803 USA. [Chakraborty, Nilay; Toner, Mehmet] Harvard Univ, Sch Med, Ctr Engn Med & Surg Serv, Shriners Hosp Children, Boston, MA 02114 USA. [Chakraborty, Nilay; Toner, Mehmet] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Menze, Michael A.] Eastern Illinois Univ, Dept Biol Sci, Charleston, IL 61920 USA. RP Toner, M (reprint author), Harvard Univ, Sch Med, Ctr Engn Med & Surg Serv, Shriners Hosp Children, Boston, MA 02114 USA. EM mehmet_toner@hms.harvard.edu; shand@lsu.edu OI Menze, Michael/0000-0003-1072-5462 FU National Institutes of Health [2R01 DK046270-14A1]; National Science Foundation [IOS-0920254] FX We thank Dr. Takahiro Kikawada (Japanese National Institute of Agrobiological Sciences) for providing the original vector encoding the trehalose transporter, Daniel Moore (Louisiana State University) for assisting with trehalose measurements, and staff of the Louisiana State University Socolofsky Microscopy Center and Dr. David Burk (Cell Biology and Bioimaging Core, Pennington Biomedical Research Center) for assisting with imaging studies. This work was supported by National Institutes of Health Grant 2R01 DK046270-14A1 and National Science Foundation Grant IOS-0920254. NR 56 TC 22 Z9 22 U1 2 U2 42 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 18 PY 2012 VL 109 IS 51 BP 20859 EP 20864 DI 10.1073/pnas.1214893109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 065BZ UT WOS:000313123700030 PM 23185012 ER PT J AU Kramer, MA Truccolo, W Eden, UT Lepage, KQ Hochberg, LR Eskandar, EN Madsen, JR Lee, JW Maheshwari, A Halgren, E Chu, CJ Cash, SS AF Kramer, Mark A. Truccolo, Wilson Eden, Uri T. Lepage, Kyle Q. Hochberg, Leigh R. Eskandar, Emad N. Madsen, Joseph R. Lee, Jong W. Maheshwari, Atul Halgren, Eric Chu, Catherine J. Cash, Sydney S. TI Human seizures self-terminate across spatial scales via a critical transition SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE critical slowing down; epilepsy; electrocorticogram; local field potential ID EARLY-WARNING SIGNALS; EPILEPTIC SEIZURES; CATASTROPHIC SHIFTS; ORGANIZED PATCHINESS; DYNAMICAL DISEASES; WORKING-MEMORY; BRAIN SYSTEMS; MODEL; OSCILLATIONS; SYNCHRONIZATION AB Why seizures spontaneously terminate remains an unanswered fundamental question of epileptology. Here we present evidence that seizures self-terminate via a discontinuous critical transition or bifurcation. We show that human brain electrical activity at various spatial scales exhibits common dynamical signatures of an impending critical transition-slowing, increased correlation, and flickering-in the approach to seizure termination. In contrast, prolonged seizures (status epilepticus) repeatedly approach, but do not cross, the critical transition. To support these results, we implement a computational model that demonstrates that alternative stable attractors, representing the ictal and postictal states, emulate the observed dynamics. These results suggest that self-terminating seizures end through a common dynamical mechanism. This description constrains the specific biophysical mechanisms underlying seizure termination, suggests a dynamical understanding of status epilepticus, and demonstrates an accessible system for studying critical transitions in nature. C1 [Kramer, Mark A.; Eden, Uri T.; Lepage, Kyle Q.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Truccolo, Wilson] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Truccolo, Wilson; Hochberg, Leigh R.] Brown Univ, Inst Brain Sci, Providence, RI 02912 USA. [Truccolo, Wilson; Hochberg, Leigh R.; Maheshwari, Atul; Chu, Catherine J.; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Truccolo, Wilson; Hochberg, Leigh R.] Dept Vet Affairs, Rehabil Res & Dev Serv, Providence, RI 02908 USA. [Hochberg, Leigh R.; Eskandar, Emad N.; Maheshwari, Atul; Chu, Catherine J.; Cash, Sydney S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hochberg, Leigh R.] Brown Univ, Sch Engn, Providence, RI 02912 USA. [Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Eskandar, Emad N.] Massachusetts Gen Hosp, Nayef Al Rodhan Labs Cellular Neurosurg & Neurosu, Boston, MA 02114 USA. [Madsen, Joseph R.] Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Madsen, Joseph R.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Lee, Jong W.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Halgren, Eric] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Halgren, Eric] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Halgren, Eric] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. RP Kramer, MA (reprint author), Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. EM mak@bu.edu RI Kramer, Mark/A-1291-2014 FU National Institute of Neurological Disorders and Stroke (NINDS) [SNS062092]; Burroughs Wellcome Fund; National Institutes of Neurological Disorders [K01 NS057389, R01NS079533]; NINDS [R01NS072023] FX We thank the patients who participated in this study, as well as the nursing and physician staff. We also thank Jason Naftulin for technical assistance and Roger Traub, Nancy Kopell, Matt Bianchi, Brandon Westover, and Andrew Cole for critical reading of the manuscript. This research is supported by National Institute of Neurological Disorders and Stroke (NINDS) Grant SNS062092 (to S.S.C.). M.A.K. holds a Career Award at the Scientific Interface from the Burroughs Wellcome Fund, and W.T. holds a Career Award K01 NS057389 from the National Institutes of Neurological Disorders. This work was also supported by Award R01NS072023 from the NINDS (to S.S.C., U.T.E., and M.A.K.), and by Award R01NS079533 from the National Institutes of Neurological Disorders (to W.T.). NR 51 TC 49 Z9 49 U1 3 U2 27 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 18 PY 2012 VL 109 IS 51 BP 21116 EP 21121 DI 10.1073/pnas.1210047110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 065BZ UT WOS:000313123700074 PM 23213262 ER PT J AU Kimball, AB Kerdel, F Adams, D Mrowietz, U Gelfand, JM Gniadecki, R Prens, EP Schlessinger, J Zouboulis, CC van der Zee, HH Rosenfeld, M Mulani, P Gu, YH Paulson, S Okun, M Jemec, GBE AF Kimball, Alexa B. Kerdel, Francisco Adams, David Mrowietz, Ulrich Gelfand, Joel M. Gniadecki, Robert Prens, Errol P. Schlessinger, Joel Zouboulis, Christos C. van der Zee, Hessel H. Rosenfeld, Marie Mulani, Parvez Gu, Yihua Paulson, Susan Okun, Martin Jemec, Gregor B. E. TI Adalimumab for the Treatment of Moderate to Severe Hidradenitis Suppurativa A Parallel Randomized Trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID QUALITY-OF-LIFE; CONTROLLED CROSSOVER TRIAL; DOUBLE-BLIND; CLINDAMYCIN; INFLIXIMAB; MORBIDITY; SMOKING; ALPHA AB Background: Hidradenitis suppurativa (HS) is a chronic, painful skin disease characterized by abscesses, nodules, and draining fistulas in the axilla and groin of young adults. Objective: To evaluate the efficacy and safety of adalimumab, an anti-tumor necrosis factor-alpha antibody, in patients with moderate to severe HS. Design: Phase 2, parallel, randomized, placebo-controlled trial consisting of a blinded 16-week period (period 1) and an open-label 36-week period (period 2). All study personnel, investigators, and patients remained blinded to treatment group throughout the study. (ClinicalTrials.gov: NCT00918255) Setting: 26 academic and private practice medical centers in the United States and Europe. Patients: 154 adult patients with moderate to severe HS who were unresponsive or intolerant to oral antibiotics. Intervention: Patients were assigned in a 1: 1: 1 ratio to adalimumab, 40 mg/wk; adalimumab, 40 mg every other week (EOW); or placebo. All patients received adalimumab, 40 mg EOW, at the beginning of period 2 but switched to weekly dosing if the response was suboptimal (HS Physician's Global Assessment [PGA] score of moderate or worse) at weeks 28 or 31. Measurements: The primary outcome measure (clinical response) was the proportion of patients achieving an HS-PGA score of clear, minimal, or mild with at least a 2-grade improvement relative to baseline at week 16. Results: At week 16, 3.9% of placebo patients (2 of 51), 9.6% of EOW patients (5 of 52), and 17.6% of weekly patients (9 of 51) achieved clinical response (EOW vs. placebo strata-adjusted difference, 5.6% [95% CI, -4.0% to 15.3%]; P = 0.25; weekly vs. placebo strata-adjusted difference, 13.7% [CI, 1.7% to 25.7%]; P = 0.025). Serious adverse event rates were 3.9%, 5.8%, and 7.8% for placebo, EOW, and weekly patients, respectively (EOW vs. placebo difference, 1.8% [CI, -6.4% to 10.1%]; weekly vs. placebo difference, 3.9% [CI, -5.2% to 13.0%]). Significantly greater improvements in patient-reported outcomes and pain were seen in the weekly dosing group than in the placebo group. A decrease in response was seen after the switch from weekly to EOW dosing in period 2. Limitations: Weeks 16 to 52 of the study were open-label. The study was not powered to assess the risk for known serious adverse effects of adalimumab, such as tuberculosis, other serious infections, and demyelinating disorders. Conclusion: Adalimumab dosed once per week alleviates moderate to severe HS. C1 [Kimball, Alexa B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Clin Unit Res Trials & Outcomes Skin, Boston, MA 02114 USA. Florida Acad Dermatol Ctr, Miami, FL USA. Penn State Hershey Med Ctr, Hershey, PA USA. Univ Med Ctr Schleswig Holstein, Kiel, Germany. Univ Penn, Philadelphia, PA 19104 USA. Bispebjerg Hosp, DK-2400 Copenhagen, Denmark. Univ Copenhagen, Copenhagen, Denmark. Erasmus MC, Rotterdam, Netherlands. Skin Specialists PC, Omaha, NE USA. Dessau Med Ctr, Dessau, Germany. Abbott Labs, Abbott Pk, IL 60064 USA. RP Kimball, AB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Clin Unit Res Trials & Outcomes Skin, 50 Staniford St 246, Boston, MA 02114 USA. EM harvardskinstudies@partners.org RI Dr. Zouboulis, Christos/I-4493-2013; Gniadecki, Robert/A-5696-2010; OI Dr. Zouboulis, Christos/0000-0003-1646-2608; Gniadecki, Robert/0000-0002-2310-8300; Prens, Errol/0000-0002-8158-660X; Jemec, Gregor/0000-0002-0712-2540 FU Abbott Laboratories FX Abbott Laboratories. NR 29 TC 95 Z9 97 U1 3 U2 19 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 18 PY 2012 VL 157 IS 12 BP 846 EP U180 DI 10.7326/0003-4819-157-12-201212180-00004 PG 19 WC Medicine, General & Internal SC General & Internal Medicine GA 057SB UT WOS:000312583200014 PM 23247938 ER PT J AU Martinez, ME Thompson, P Messer, K Ashbeck, EL Lieberman, DA Baron, JA Ahnen, DJ Robertson, DJ Jacobs, ET Greenberg, ER Cross, AJ Atkin, W AF Martinez, Maria Elena Thompson, Patricia Messer, Karen Ashbeck, Erin L. Lieberman, David A. Baron, John A. Ahnen, Dennis J. Robertson, Douglas J. Jacobs, Elizabeth T. Greenberg, E. Robert Cross, Amanda J. Atkin, Wendy TI One-Year Risk for Advanced Colorectal Neoplasia: US Versus UK Risk-Stratification Guidelines SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID PRIMARY-CARE PHYSICIANS; SOCIETY TASK-FORCE; NATIONAL-SURVEY; COLONOSCOPY SURVEILLANCE; ADENOMATOUS POLYPS; CONSENSUS UPDATE; CANCER; POLYPECTOMY; RECOMMENDATIONS; RECURRENCE AB Background: Guidelines from the United Kingdom and the United States on risk stratification after polypectomy differ, as do recommended surveillance intervals. Objective: To compare risk for advanced colorectal neoplasia at 1-year colonoscopy among patients cross-classified by U. S. and U. K. surveillance guidelines. Design: Pooled analysis of 4 prospective studies between 1984 and 1998. Setting: Academic and private clinics in the United States. Patients: 3226 postpolypectomy patients with 6- to 18-month follow-up colonoscopy. Measurements: Rates of advanced neoplasia (an adenoma >= 1 cm, high-grade dysplasia, >25% villous architecture, or invasive cancer) at 1 year, compared across U. S. and U. K. risk categories. Results: Advanced neoplasia was detected 1 year after polypectomy in 3.8% (95% CI, 2.7% to 4.9%) of lower-risk patients and 11.2% (CI, 9.8% to 12.6%) of higher-risk patients by U. S. criteria. According to U. K. criteria, 4.4% (CI, 3.3% to 5.4%) of low-risk patients, 9.9% (CI, 8.3% to 11.5%) of intermediate-risk patients, and 18.7% (CI, 14.8% to 22.5%) of high-risk patients presented with advanced neoplasia; U. K. high-risk patients comprised 12.1% of all patients. All U. S. lower-risk patients were low-risk by U. K. criteria; however, more patients were classified as low-risk, because the U. K. guidelines do not consider histologic features. Higher-risk U. S. patients were distributed across the 3 U. K. categories. Among all patients with advanced neoplasia, 26.3% were reclassified by the U. K. criteria to a higher-risk category and 7.0% to a lower-risk category, with a net 19.0% benefiting from detection 2 years earlier. Overall, substitution of U. K. for U. S. guidelines resulted in an estimated 0.03 additional colonoscopy every 5 years per patient. Limitations: Patients were enrolled 15 to 20 years ago, and quality measures for colonoscopy were unavailable. Patients lacking follow-up colonoscopy or with surveillance colonoscopy after 6 to 18 months and those with cancer or insufficient baseline adenoma characteristics were excluded (2076 of 5302). Conclusion: Application of the U. K. guidelines in the United States could identify a subset of high-risk patients who may warrant a 1-year clearing colonoscopy without substantially increasing rates of colonoscopy. C1 [Martinez, Maria Elena] Univ Calif San Diego, Moores Canc Ctr, Sch Med, La Jolla, CA 92093 USA. Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. Univ Arizona, Coll Med, Tucson, AZ USA. Univ Arizona, Mel & Enid Zuckerman Arizona Coll Publ Hlth, Tucson, AZ USA. Portland VA Med Ctr, Portland, OR USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Univ Colorado, Sch Med, Denver, CO USA. White River Junct Vet Affairs Med Ctr, White River Jct, VT USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NCI, Rockville, MD USA. Univ London Imperial Coll Sci Technol & Med, London, England. RP Martinez, ME (reprint author), Univ Calif San Diego, Moores Canc Ctr, Sch Med, 3855 Hlth Sci Dr 0901, La Jolla, CA 92093 USA. EM e8martinez@ucsd.edu FU European Union Health Programme [2005317]; International Agency for Research on Cancer; National Cancer Institute [CA-41108, CA-23074, CA95060, CA37287, CA104869, CA23108, CA59005, CA26852]; European Union Public Health Programme FX Grant Support: By the European Union Health Programme (Development of European Guidelines for Quality Assurance of Colorectal Cancer Screening; grant agreement 2005317); the International Agency for Research on Cancer; and the U.S. Public Health Service grants CA-41108, CA-23074, CA95060, CA37287, CA104869, CA23108, CA59005, and CA26852 from the National Cancer Institute.; European Union Public Health Programme. NR 36 TC 18 Z9 18 U1 1 U2 5 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 18 PY 2012 VL 157 IS 12 BP 856 EP U192 DI 10.7326/0003-4819-157-12-201212180-00005 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 057SB UT WOS:000312583200015 PM 23247939 ER PT J AU Rigotti, NA Wakefield, M AF Rigotti, Nancy A. Wakefield, Melanie TI Real People, Real Stories: A New Mass Media Campaign That Could Help Smokers Quit SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID SMOKING-CESSATION; COMMUNICATION C1 [Rigotti, Nancy A.] Massachusetts Gen Hosp, Gen Med Div, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Canc Council Victoria, Ctr Behav Res Canc, Melbourne, Vic, Australia. RP Rigotti, NA (reprint author), Massachusetts Gen Hosp, Gen Med Div, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM nrigotti@partners.org RI Wakefield, Melanie/E-5019-2012 FU NHLBI NIH HHS [K24 HL004440] NR 18 TC 14 Z9 15 U1 1 U2 8 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 18 PY 2012 VL 157 IS 12 BP 907 EP U125 DI 10.7326/0003-4819-156-1-201201010-00541 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 057SB UT WOS:000312583200021 PM 23007853 ER PT J AU Chen, XY Pravetoni, M Bhayana, B Pentel, PR Wu, MX AF Chen, Xinyuan Pravetoni, Marco Bhayana, Brijesh Pentel, Paul R. Wu, Mei X. TI High immunogenicity of nicotine vaccines obtained by intradermal delivery with safe adjuvants SO VACCINE LA English DT Article DE Nicotine vaccine; Adjuvant; Intradermal delivery; Immunogenicity; Addiction; Immunotherapy ID TOBACCO DEPENDENCE; SMOKING-CESSATION; INFLUENZA VACCINE; IMMUNIZATION; TRIAL; IMMUNOTHERAPY; ANTIBODIES; INJECTION; INCREASE; SYSTEM AB Immunotherapy for tobacco addiction may offer a safe, alternative treatment if the immunogenicity of the current nicotine vaccines can be improved. We show here that intradermal (ID) immunization induces the production of antibody directed against nicotine (NicAb) at a much higher level than conventional intramuscular (IM) immunization. The magnitude and duration of NicAb production was further increased robustly by non-inflammatory laser vaccine adjuvant (LVA), slightly inflammatory monophosphoryl lipid A (MPL) or a combination of MPL and CpG adjuvants. Consequently, significantly fewer vaccination doses were required to attain a high level of NicAb production for an extended period of time and reduce nicotine entry into the brain in the presence of LVA, MPL or MPL/CpG adjuvant, respectively. Yet, the potency of these adjuvants to augment ID nicotine vaccine immunogenicity came at the expense of local skin reactogenicity, with LVA causing little skin reaction and MPL/CpG stimulating overt skin irritation. These observations underscore a necessity of a balance between optimal adjuvant potency and undesired local reactogenicity. In summary, our study presents a novel approach to significantly improve nicotine vaccine immunogenicity by a combination of safe cutaneous vaccine adjuvants with ID immunization. (c) 2012 Elsevier Ltd. All rights reserved. C1 [Chen, Xinyuan; Bhayana, Brijesh; Wu, Mei X.] Harvard Univ, Massachusetts Gen Hosp, Wellman Ctr Photomed, Dept Dermatol,Med Sch HMS, Boston, MA 02114 USA. [Pravetoni, Marco; Pentel, Paul R.] Minneapolis Med Res Fdn Inc, Minneapolis, MN USA. [Pravetoni, Marco; Pentel, Paul R.] Univ Minnesota, Sch Med, Dept Pharmacol, Minneapolis, MN 55455 USA. [Pravetoni, Marco; Pentel, Paul R.] Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA. [Wu, Mei X.] Harvard MIT Div Hlth Sci & Technol HST, Cambridge, MA USA. RP Wu, MX (reprint author), Harvard Univ, Massachusetts Gen Hosp, Wellman Ctr Photomed, Dept Dermatol,Med Sch HMS, 50 Blossom St,Edwards 222, Boston, MA 02114 USA. EM mwu2@partners.org FU National Institutes of Health [AI070785, RC1 DA028378, DA10714] FX We would like to thank Ms. Florence Lin, Dr. Xiao-Ming Lu, Dr. Yong-Ming Yu, and Dr. Alan J. Fischerman (Department of Surgery, Massachusetts General Hospital) for assistance in setting up gas chromatography-mass spectrometry (GC-MS) method for nicotine detection in our preliminary studies, Zhanliang Wei to collect blood and measure NicAb titer by ELISA, and Theresa Harmon (Departments of Pharmacology and Medicine, University of Minnesota Medical School) for measurement of brain and serum nicotine concentrations. This work was supported by the National Institutes of Health Grants AI070785 and RC1 DA028378 (M.X.W.) and DA10714 (P.R.P.). NR 32 TC 19 Z9 20 U1 0 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD DEC 17 PY 2012 VL 31 IS 1 BP 159 EP 164 DI 10.1016/j.vaccine.2012.10.069 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 067PA UT WOS:000313306400022 PM 23123021 ER PT J AU Nishida, A Nagahama, K Imaeda, H Ogawa, A Lau, CW Kobayashi, T Hisamatsu, T Preffer, FI Mizoguchi, E Ikeuchi, H Hibi, T Fukuda, M Andoh, A Blumberg, RS Mizoguchi, A AF Nishida, Atsushi Nagahama, Kiyotaka Imaeda, Hirotsugu Ogawa, Atsuhiro Lau, Cindy W. Kobayashi, Taku Hisamatsu, Tadakazu Preffer, Frederic I. Mizoguchi, Emiko Ikeuchi, Hiroki Hibi, Toshifumi Fukuda, Minoru Andoh, Akira Blumberg, Richard S. Mizoguchi, Atsushi TI Inducible colitis-associated glycome capable of stimulating the proliferation of memory CD4(+) T cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID KINASE-C-THETA; INFLAMMATORY-BOWEL-DISEASE; NF-KAPPA-B; O-LINKED OLIGOSACCHARIDES; INTESTINAL INFLAMMATION; IMMUNE-RESPONSES; IMMUNOLOGICAL SYNAPSE; GLYCAN INTERACTIONS; TRANSGENIC MICE; ACTIVATION AB Immune responses are modified by a diverse and abundant repertoire of carbohydrate structures on the cell surface, which is known as the glycome. In this study, we propose that a unique glycome that can be identified through the binding of galectin-4 is created on local, but not systemic, memory CD4(+) T cells under diverse intestinal inflammatory conditions, but not in the healthy state. The colitis-associated glycome (CAG) represents an immature core 1-expressing O-glycan. Development of CAG may be mediated by down-regulation of the expression of core-2 beta 1,6-N-acetylglucosaminyltransferase (C2GnT) 1, a key enzyme responsible for the production of core-2 O-glycan branch through addition of N-acetylglucosamine (GlcNAc) to a core-1 O-glycan structure. Mechanistically, the CAG seems to contribute to super raft formation associated with the immunological synapse on colonic memory CD4(+) T cells and to the consequent stabilization of protein kinase C. activation, resulting in the stimulation of memory CD4(+) T cell expansion in the inflamed intestine. Functionally, CAG-mediated CD4(+) T cell expansion contributes to the exacerbation of T cell-mediated experimental intestinal inflammations. Therefore, the CAG may be an attractive therapeutic target to specifically suppress the expansion of effector memory CD4(+) T cells in intestinal inflammation such as that seen in inflammatory bowel disease. C1 [Nishida, Atsushi; Lau, Cindy W.; Mizoguchi, Atsushi] Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02114 USA. [Preffer, Frederic I.] Massachusetts Gen Hosp, Expt Pathol Unit, Boston, MA 02114 USA. [Mizoguchi, Emiko] Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. [Mizoguchi, Emiko; Mizoguchi, Atsushi] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Nishida, Atsushi; Lau, Cindy W.; Preffer, Frederic I.; Mizoguchi, Atsushi] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Mizoguchi, Emiko; Blumberg, Richard S.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Nagahama, Kiyotaka] Yokohama City Univ, Sch Med, Dept Pathol, Yokohama, Kanagawa 2360004, Japan. [Imaeda, Hirotsugu; Ogawa, Atsuhiro; Andoh, Akira] Shiga Univ Med Sci, Dept Med, Otsu, Shiga 5202192, Japan. [Kobayashi, Taku; Hisamatsu, Tadakazu; Hibi, Toshifumi] Keio Univ, Sch Med, Dept Med, Tokyo 1608582, Japan. [Ikeuchi, Hiroki] Hyogo Coll Med, Dept Surg, Nishinomiya, Hyogo 6638501, Japan. [Fukuda, Minoru] La Jolla Canc Res Fdn, Canc Res Ctr, Burnham Inst Med Res, La Jolla, CA 92037 USA. [Blumberg, Richard S.] Brigham & Womens Hosp, Gastroenterol Unit, Boston, MA 02115 USA. RP Mizoguchi, A (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02114 USA. EM amizoguchi@partners.org OI Imaeda, Hirotsugu/0000-0002-5516-8527 FU National Institutes of Health (NIH) [R01DK064351, RC1DK086242, R01AI081807, R01DK080070]; Harry B. and Leona Helmsley Charitable Trust; Crohn's and Colitis Foundation of America FX This study was supported primarily by National Institutes of Health (NIH) grant R01DK064351, and partially by NIH grants RC1DK086242 and R01AI081807, the Harry B. and Leona Helmsley Charitable Trust, Crohn's and Colitis Foundation of America (A. Mizoguchi), and NIH grant R01DK080070 (E. Mizoguchi). NR 44 TC 12 Z9 12 U1 1 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 17 PY 2012 VL 209 IS 13 BP 2383 EP 2394 DI 10.1084/jem.20112631 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 057CQ UT WOS:000312539900006 PM 23209314 ER PT J AU Gagnon, E Schubert, DA Gordo, S Chu, HH Wucherpfennig, KW AF Gagnon, Etienne Schubert, David A. Gordo, Susana Chu, H. Hamlet Wucherpfennig, Kai W. TI Local changes in lipid environment of TCR microclusters regulate membrane binding by the CD3 epsilon cytoplasmic domain SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID T-CELL-ACTIVATION; IMMUNOLOGICAL SYNAPSE; RECEPTOR MICROCLUSTERS; SUBUNIT CONTAINS; ANTIGEN RECEPTOR; SURFACE-CHARGE; LIVING CELLS; MAST-CELLS; PROTEIN; PHOSPHATIDYLSERINE AB The CD3 epsilon and xi cytoplasmic domains of the T cell receptor bind to the inner leaflet of the plasma membrane (PM), and a previous nuclear magnetic resonance structure showed that both tyrosines of the CD3 epsilon immunoreceptor tyrosine-based activation motif partition into the bilayer. Electrostatic interactions between acidic phospholipids and clusters of basic CD3 epsilon residues were previously shown to be essential for CD3 epsilon and xi membrane binding. Phosphatidylserine (PS) is the most abundant negatively charged lipid on the inner leaflet of the PM and makes a major contribution to membrane binding by the CD3 epsilon cytoplasmic domain. Here, we show that TCR triggering by peptide-MHC complexes induces dissociation of the CD3 epsilon cytoplasmic domain from the plasma membrane. Release of the CD3 epsilon cytoplasmic domain from the membrane is accompanied by a substantial focal reduction in negative charge and available PS in TCR microclusters. These changes in the lipid composition of TCR microclusters even occur when TCR signaling is blocked with a Src kinase inhibitor. Local changes in the lipid composition of TCR microclusters thus render the CD3 epsilon cytoplasmic domain accessible during early stages of T cell activation. C1 [Gagnon, Etienne; Schubert, David A.; Gordo, Susana; Chu, H. Hamlet; Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Program Immunol, Boston, MA 02115 USA. [Gagnon, Etienne] Inst Rech Immunol & Canc, Dept Microbiol & Immunol, Montreal, PQ H3T 1J4, Canada. RP Wucherpfennig, KW (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM etienne.gagnon@umontreal.ca; kai_wucherpfennig@dfci.harvard.edu FU National Institutes of Health [R01AI054520, P01AI045757]; Cancer Research Institute FX This work was supported by grants from the National Institutes of Health (R01AI054520 and P01AI045757 to K.W. Wucherpfennig) and fellowships by the Cancer Research Institute (to E. Gagnon, D.A. Schubert, and H.H. Chu). NR 47 TC 26 Z9 26 U1 0 U2 11 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 17 PY 2012 VL 209 IS 13 BP 2423 EP 2439 DI 10.1084/jem.20120790 PG 17 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 057CQ UT WOS:000312539900009 PM 23166358 ER PT J AU Chen, MH Huang, J Chen, WM Larson, MG Fox, CS Vasan, RS Seshadri, S O'Donnell, CJ Yang, Q AF Chen, Ming-Huei Huang, Jie Chen, Wei-Min Larson, Martin G. Fox, Caroline S. Vasan, Ramachandran S. Seshadri, Sudha O'Donnell, Christopher J. Yang, Qiong TI Using Family-Based Imputation in Genome-Wide Association Studies with Large Complex Pedigrees: The Framingham Heart Study SO PLOS ONE LA English DT Article ID GENETIC-LOCI; ALZHEIMER-DISEASE; URIC-ACID; FIBRINOGEN; VARIANTS; DESIGN; RISK; MAPS AB Imputation has been widely used in genome-wide association studies (GWAS) to infer genotypes of un-genotyped variants based on the linkage disequilibrium in external reference panels such as the HapMap and 1000 Genomes. However, imputation has only rarely been performed based on family relationships to infer genotypes of un-genotyped individuals. Using 8998 Framingham Heart Study (FHS) participants genotyped with Affymetrix 550K SNPs, we imputed genotypes of same set of SNPs for additional 3121 participants, most of whom were never genotyped due to lack of DNA sample. Prior to imputation, 122 pedigrees were too large to be handled by the imputation software Merlin. Therefore, we developed a novel pedigree splitting algorithm that can maximize the number of genotyped relatives for imputing each un-genotyped individual, while keeping new sub-pedigrees under a pre-specified size. In GWAS of four phenotypes available in FHS (Alzheimer disease, circulating levels of fibrinogen, high-density lipoprotein cholesterol, and uric acid), we compared results using genotyped individuals only with results using both genotyped and imputed individuals. We studied the impact of applying different imputation quality filtering thresholds on the association results and did not found a universal threshold that always resulted in a more significant p-value for previously identified loci. However most of these loci had a lower p-value when we only included imputed genotypes with with >= 60% SNP- and >= 50% person-specific imputation certainty. In summary, we developed a novel algorithm for splitting large pedigrees for imputation and found a plausible imputation quality filtering threshold based on FHS. Further examination may be required to generalize this threshold to other studies. C1 [Chen, Ming-Huei; Larson, Martin G.; Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Chen, Ming-Huei; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Chen, Ming-Huei; Huang, Jie; Larson, Martin G.; Fox, Caroline S.; Vasan, Ramachandran S.; Seshadri, Sudha; O'Donnell, Christopher J.; Yang, Qiong] NHLBI, Framingham Heart Study, Framingham, MA USA. [Huang, Jie] Wellcome Trust Sanger Inst, Cambridge, England. [Chen, Wei-Min] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Hypertens & Diabet, Boston, MA USA. [O'Donnell, Christopher J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Cardiol, Boston, MA USA. RP Yang, Q (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. EM qyang@bu.edu RI Yang, Qiong/G-5438-2014; OI Yang, Qiong/0000-0002-3658-1375; Larson, Martin/0000-0002-9631-1254; Seshadri, Sudha/0000-0001-6135-2622; Ramachandran, Vasan/0000-0001-7357-5970 FU National Heart, Lung, and Blood Institute [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; NIH [R01 NS017950-28, R01-HL093328-01]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine; Boston Medical Center; [R01HL093328]; [R01HL093029]; [R01NS017950] FX The authors were supported in part by the National Heart, Lung, and Blood Institute's Framingham Heart Study (Con-tract No. N01-HC-25195) and grant numbers R01HL093328, R01HL093029, R01NS017950 and R01HL093029. The research was conducted in part using data and resources from the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine. The analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. This work was partially supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195), its contract with Affymetrix, Inc for genotyping services (Contract No. N02-HL-6-4278) and NIH grants R01 NS017950-28 and R01-HL093328-01. A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 23 TC 7 Z9 7 U1 1 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 17 PY 2012 VL 7 IS 12 AR e51589 DI 10.1371/journal.pone.0051589 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 055RZ UT WOS:000312435900032 PM 23284720 ER PT J AU Rohrbach, J Davis, O Pacheco, Y McLean, A Haghighat, R Sage, P Sharpe, A Kaufmann, D Kavanagh, D AF Rohrbach, Janine Davis, Oliver Pacheco, Yovana McLean, Anna Haghighat, Roxanna Sage, Peter Sharpe, Arlene Kaufmann, Daniel Kavanagh, Daniel TI Human brain microvascular endothelial cells present viral peptides to HLA-class I-restricted CD8 T cells SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 11th International Congress of Neuroimmunology (ISNI) CY NOV 04-08, 2012 CL Boston, MA SP European Sch Neuroimmunol, Int Soc Neuroimmunol (ISNI) C1 [Rohrbach, Janine; Davis, Oliver; Pacheco, Yovana; McLean, Anna; Haghighat, Roxanna; Kaufmann, Daniel; Kavanagh, Daniel] Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA. [Sage, Peter; Sharpe, Arlene] Harvard Univ, Sch Med, Dana Farber Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD DEC 15 PY 2012 VL 253 IS 1-2 BP 25 EP 26 PG 2 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 060GP UT WOS:000312764800067 ER PT J AU Kaliszewska, A Liu, QQ Keenan, BT Xia, ZQ Berger, CT Lee, M Alter, G De Jager, PL AF Kaliszewska, Anna Liu, Qingquan Keenan, Brendan T. Xia, Zongqi Berger, Christoph T. Lee, Michelle Alter, Galit De Jager, Philip L. TI The multiple sclerosis susceptibility MAPK1 allele is associated with decreased degranulation by bulk NK cells and CD56dim NK cells in response to MHC class I-deficient B cell line SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 11th International Congress of Neuroimmunology (ISNI) CY NOV 04-08, 2012 CL Boston, MA SP European Sch Neuroimmunol, Int Soc Neuroimmunol (ISNI) C1 [Kaliszewska, Anna; Keenan, Brendan T.; Xia, Zongqi; Lee, Michelle; De Jager, Philip L.] Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Neurol & Psychiat, Program Translat NeuroPsychiat Genom,Inst Neurosc, Boston, MA 02115 USA. [Liu, Qingquan; Berger, Christoph T.; Alter, Galit] Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02114 USA. [Liu, Qingquan; Berger, Christoph T.; Alter, Galit] Harvard Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD DEC 15 PY 2012 VL 253 IS 1-2 BP 42 EP 42 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 060GP UT WOS:000312764800113 ER PT J AU Butovsky, O Siddiqui, S Gabriely, G Lanser, A Dake, B Gopal, M Gali, R Iyer, L Lawson, R Berry, J Krichevsky, A Cudkowicz, M Weiner, H AF Butovsky, Oleg Siddiqui, Shafiuddin Gabriely, Galina Lanser, Amanda Dake, Ben Gopal, Murugaiyan Gali, Reddy Iyer, Lakshmanan Lawson, Robert Berry, James Krichevsky, Anna Cudkowicz, Merit Weiner, Howard TI Modulation of inflammatory monocytes with a unique microRNA-gene signature ameliorates ALS mice SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 11th International Congress of Neuroimmunology (ISNI) CY NOV 04-08, 2012 CL Boston, MA SP European Sch Neuroimmunol, Int Soc Neuroimmunol (ISNI) C1 [Butovsky, Oleg; Siddiqui, Shafiuddin; Gabriely, Galina; Lanser, Amanda; Gopal, Murugaiyan; Krichevsky, Anna; Weiner, Howard] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol,Ctr Neurol Dis, Boston, MA 02115 USA. [Iyer, Lakshmanan] TUFTS, Dept Neurosci, Boston, MA USA. [Gali, Reddy] Haravrd, Harvard Dept Bioinformat, Boston, MA USA. [Lawson, Robert; Berry, James; Cudkowicz, Merit] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Neurol Clin Trial Unit,Med Sch, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD DEC 15 PY 2012 VL 253 IS 1-2 BP 63 EP 63 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 060GP UT WOS:000312764800169 ER PT J AU Arvold, ND Punglia, RS Hughes, ME Jiang, W Edge, SB Javid, SH Laronga, C Niland, JC Theriault, RL Weeks, JC Wong, YN Lee, SJ Hassett, MJ AF Arvold, Nils D. Punglia, Rinaa S. Hughes, Melissa E. Jiang, Wei Edge, Stephen B. Javid, Sara H. Laronga, Christine Niland, Joyce C. Theriault, Richard L. Weeks, Jane C. Wong, Yu-Ning Lee, Sandra J. Hassett, Michael J. TI Pathologic Characteristics of Second Breast Cancers After Breast Conservation for Ductal Carcinoma In Situ SO CANCER LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY JUN 03-08, 2011 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) DE ductal carcinoma in situ; breast-conserving therapy; lumpectomy; radiation; tamoxifen; second breast cancer; contralateral breast cancer; grade; estrogen receptor ID SURGICAL ADJUVANT BREAST; NUYS PROGNOSTIC INDEX; CONSERVING THERAPY; EUROPEAN ORGANIZATION; RADIATION-THERAPY; DEFINITIVE BREAST; LOCAL RECURRENCE; WOMEN; SURGERY; RADIOTHERAPY AB BACKGROUND: The number of women diagnosed with ductal carcinoma in situ (DCIS) is increasing. Although many eventually develop a second breast cancer (SBC), little is known about the characteristics of SBCs. The authors described the characteristics of SBC and examined associations between the pathologic features of SBC and index DCIS cases. METHODS: Women were identified in the National Comprehensive Cancer Network Outcomes Database who were diagnosed with DCIS from 1997 to 2008 and underwent lumpectomy and who subsequently developed SBC (including DCIS or invasive disease that occurred in the ipsilateral or contralateral breast). The Fisher exact test and the Spearman test were used to examine associations between the pathologic characteristics of SBC and index DCIS cases. RESULTS: Among 2636 women who underwent lumpectomy for DCIS, 150 (5.7%) experienced an SBC after a median of 55.5 months of follow-up. Of these 150 women, 105 (70%) received adjuvant radiotherapy, and 50 (33.3%) received tamoxifen for their index DCIS. SBCs were ipsilateral in 54.7% of women and invasive in 50.7% of women. Among the index DCIS cases, 60.6% were estrogen receptor (ER)-positive, and 54% were high grade, whereas 77.5% of SBCs were ER-positive, and 48.2% were high grade. Tumor grade (P=.003) and ER status (P=.02) were associated significantly between index DCIS and SBC, whereas tumor size was not (P=.87). CONCLUSIONS: After breast conservation for DCIS, SBC in either breast exhibited pathologic characteristics similar to the index DCIS, suggesting that women with DCIS may be at risk for developing subsequent breast cancers of a similar phenotype. Cancer 2012;118:6022-30. (C) 2012 American Cancer Society. C1 [Arvold, Nils D.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA USA. [Punglia, Rinaa S.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Hughes, Melissa E.; Weeks, Jane C.; Wong, Yu-Ning; Hassett, Michael J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Jiang, Wei] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Edge, Stephen B.] Roswell Pk Canc Inst, Dept Surg Oncol, Buffalo, NY 14263 USA. [Edge, Stephen B.] SUNY Buffalo, Dept Surg, Buffalo, NY 14260 USA. [Javid, Sara H.] Univ Washington, Sch Med, Med Ctr, Dept Surg, Seattle, WA 98195 USA. [Laronga, Christine] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Comprehens Breast Program,Dept Womens Oncol, Tampa, FL 33612 USA. [Niland, Joyce C.] City Hope Natl Med Ctr, Dept Informat Sci, Duarte, CA 91010 USA. [Theriault, Richard L.] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. [Lee, Sandra J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Lee, Sandra J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Arvold, ND (reprint author), Brigham & Womens Hosp, Harvard Radiat Oncol Program, Dept Radiat Oncol, L-2 Level,75 Francis St, Boston, MA 02115 USA. EM narvold@partners.org RI JIANG, WEI /F-3930-2015 FU NCI NIH HHS [P50 CA089393, P50 CA89393]; PHS HHS [HHSA290200500161] NR 44 TC 8 Z9 8 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD DEC 15 PY 2012 VL 118 IS 24 BP 6022 EP 6030 DI 10.1002/cncr.27691 PG 9 WC Oncology SC Oncology GA 048KZ UT WOS:000311911600005 PM 22674478 ER PT J AU Cho, DC Hutson, TE Samlowski, W Sportelli, P Somer, B Richards, P Sosman, JA Puzanov, I Michaelson, MD Flaherty, KT Figlin, RA Vogelzang, NJ AF Cho, Daniel C. Hutson, Thomas E. Samlowski, Wolfram Sportelli, Peter Somer, Brad Richards, Paul Sosman, Jeffrey A. Puzanov, Igor Michaelson, M. Dror Flaherty, Keith T. Figlin, Robert A. Vogelzang, Nicholas J. TI Two Phase 2 Trials of the Novel Akt Inhibitor Perifosine in Patients With Advanced Renal Cell Carcinoma After Progression on Vascular Endothelial Growth Factor-Targeted Therapy SO CANCER LA English DT Article DE perifosine; renal cancer; renal cell carcinoma; Akt; Akt inhibitor; mammalian target of rapamycin ID LEUKEMIA-CELLS; APOPTOSIS; EVEROLIMUS; ACTIVATION; RAPAMYCIN; MECHANISM; MYELOMA; PATHWAY; MTOR AB BACKGROUND: The clinical activity of allosteric inhibitors of mammalian target of rapamycin (mTOR) inhibitors in renal cell carcinoma (RCC) may be limited by upstream activation of phosphatidylinositol 3 (PI3)-kinase/Akt resulting from mTOR1 inhibition. On the basis of this rationale, 2 independent phase 2 trials (Perifosine 228 and 231) were conducted to assess the efficacy and safety of the novel Akt inhibitor perifosine in patients with advanced RCC who had failed on previous vascular endothelial growth factor (VEGF)-targeted therapy. METHODS: In the Perifosine 228 trial, 24 patients with advanced RCC received oral perifosine (100 mg daily). Perifosine 231 enrolled 2 groups that received daily oral perifosine (100 mg daily): Group A comprised 32 patients who had received no prior mTOR inhibitor, and Group B comprised 18 patients who had received 1 prior mTOR inhibitor. RESULTS: In the Perifosine 228 trial, 1 patient achieved a partial response (objective response rate, 4%; 95% confidence interval, 0.7%-20%), and 11 patients (46%) had stable disease as their best response. The median progression-free survival was 14.2 weeks (95% confidence interval, 7.7-21.6 weeks). In the Perifosine 231 trial, 5 patients achieved a partial response (objective response rate, 10%; 95% confidence interval, 4.5%-22.2%) and 16 patients (32%) had stable disease as their best response. The median progression-free survival was 14 weeks (95% confidence interval, 12.9, 20.7 weeks). Overall, perifosine was well tolerated, and there were very few grade 3 and 4 events. The most common toxicities included nausea, diarrhea, musculoskeletal pain, and fatigue. CONCLUSIONS: Although perifosine demonstrated activity in patients with advanced RCC after failure on VEGF-targeted therapy, its activity was not superior to currently available second-line agents. Nonetheless, perifosine may be worthy of further study in RCC in combination with other currently available therapies. Cancer 2012;118:6055-62. (C) 2012 American Cancer Society. C1 [Cho, Daniel C.] Beth Israel Deaconess Med Ctr, Div Hematol & Oncol, Boston, MA 02215 USA. [Hutson, Thomas E.] Baylor Univ, Med Ctr, Div Oncol, Dallas, TX USA. [Sportelli, Peter] Keryx Pharmaceut Inc, New York, NY USA. [Somer, Brad] West Clin, Memphis, TN USA. [Richards, Paul] Blue Ridge Canc Care, Salem, VA USA. [Sosman, Jeffrey A.; Puzanov, Igor] Vanderbilt Ingram Canc Ctr, Div Hematol & Oncol, Nashville, TN USA. [Michaelson, M. Dror; Flaherty, Keith T.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol & Oncol, Boston, MA USA. [Flaherty, Keith T.; Figlin, Robert A.] Univ Penn, Div Hematol & Oncol, Philadelphia, PA 19104 USA. [Vogelzang, Nicholas J.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Comprehens Canc Ctr Nevada, Las Vegas, NV USA. RP Cho, DC (reprint author), 330 Brookline Ave, Boston, MA 02215 USA. EM dcho1@bidmc.harvard.edu OI Michaelson, Dror/0000-0001-9249-6338; Samlowski, Wolfram/0000-0002-0713-914X FU Keryx Pharmaceuticals; National Institute of Health/National Cancer Institute [P50CA101942] FX This study was supported by Keryx Pharmaceuticals and by a grant from the National Institute of Health/National Cancer Institute (P50CA101942). NR 22 TC 23 Z9 26 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD DEC 15 PY 2012 VL 118 IS 24 BP 6055 EP 6062 DI 10.1002/cncr.27668 PG 8 WC Oncology SC Oncology GA 048KZ UT WOS:000311911600009 PM 22674198 ER PT J AU Zhu, JY Davis, RB Stuver, SO Berry, DL Block, S Weeks, JC Weingart, SN AF Zhu, Junya 1,2 Davis, Roger B. 3 Stuver, Sherri O. 1 Berry, Donna L. 4 Block, Susan 5 Weeks, Jane C. 6 Weingart, Saul N. 1 TI A Longitudinal Study of Pain Variability and Its Correlates in Ambulatory Patients With Advanced Stage Cancer SO CANCER LA English DT Article DE pain variability; pain intensity; longitudinal study; advanced cancer; electronic medical record; tumor registry ID QUALITY-OF-LIFE; NECK-CANCER; UNITED-STATES; PREDICT SURVIVAL; PROSTATE-CANCER; PREVALENCE; MANAGEMENT; HEAD; CARE; OUTPATIENTS AB BACKGROUND: Although pain is common among patients with advanced cancer, little is known about longitudinal variability in pain intensity. For this report, the authors examined variability in pain intensity over 24 months among ambulatory patients with advanced stage cancers, associations between patient characteristics and within-patient pain variability, and the relation of pain variability to overall survival. METHODS: The sample comprised 949 patients with solid tumors who received care and reported pain scores in at least 3 different months within 24 months of their initial stage IV diagnosis during the period from 2004 to 2006. Pain intensity was measured using a scale ranging from 0 (no pain) to 10 (worst pain). Pain variability was defined as the standard deviation of the maximum monthly pain scores and was dichotomized at the 50th percentile into high and low variability groups. RESULTS: Considerable between-patient differences in pain variability (range, 0-5.77) were observed. Nonwhites, patients with a stage IV cancer diagnosed within the previous 3 months, and those with moderate or severe pain at baseline were more likely to experience high pain variability. Although patients with head and neck cancer generally had the highest pain variability, the intensity of their pain typically decreased over the disease course. High pain variability with worsening pain trajectory was associated with increased risk of death. CONCLUSIONS: Longitudinally, pain intensity was highly variable among patients with stage IV cancer. Minority patients, newly diagnosed patients, patients with head and neck cancer, and patients with moderate or severe pain at baseline were at higher risk of large fluctuations in pain intensity. Cancer 2012; 118:6278-86. (C) 2012 American Cancer Society. C1 [Zhu, Junya 1,2; Stuver, Sherri O. 1; Weingart, Saul N. 1] Dana Farber Canc Inst, Ctr Patient Safety, Boston, MA 02215 USA. [Zhu, Junya 1,2] Brandeis Univ, Heller Sch Social Policy & Management, Waltham, MA USA. [Davis, Roger B. 3] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA USA. [Berry, Donna L. 4] Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA 02215 USA. [Block, Susan 5] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02215 USA. [Weeks, Jane C. 6] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02215 USA. RP Zhu, JY (reprint author), Dana Farber Canc Inst, Ctr Patient Safety, 450 Brookline Ave, Boston, MA 02215 USA. EM junya_zhu@dfci.harvard.edu OI Stuver, Sherri/0000-0002-4027-2663 FU American Cancer Society [PEP-08-273-01-PC1] FX This research was supported by a grant (PEP-08-273-01-PC1) from the American Cancer Society. NR 50 TC 6 Z9 6 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD DEC 15 PY 2012 VL 118 IS 24 BP 6278 EP 6286 DI 10.1002/cncr.27673 PG 9 WC Oncology SC Oncology GA 048KZ UT WOS:000311911600034 PM 22674404 ER PT J AU Hebert, AM DuBoff, B Casaletto, JB Gladden, AB McClatchey, AI AF Hebert, Alan M. DuBoff, Brian Casaletto, Jessica B. Gladden, Andrew B. McClatchey, Andrea I. TI Merlin/ERM proteins establish cortical asymmetry and centrosome position SO GENES & DEVELOPMENT LA English DT Article DE Merlin/ERMs; alpha-catenin; polarity; centrosome; spindle orientation; cortical cytoskeleton ID MITOTIC SPINDLE ORIENTATION; NF2 TUMOR-SUPPRESSOR; ADHERENS JUNCTIONS; CELL-DIVISION; EPITHELIAL MORPHOGENESIS; NEUROFIBROMATOSIS TYPE-2; EXTRA CENTROSOMES; RENAL-CARCINOMA; APICAL SURFACE; CANCER-CELLS AB The ability to generate asymmetry at the cell cortex underlies cell polarization and asymmetric cell division. Here we demonstrate a novel role for the tumor suppressor Merlin and closely related ERM proteins (Ezrin, Radixin, and Moesin) in generating cortical asymmetry in the absence of external cues. Our data reveal that Merlin functions to restrict the cortical distribution of the actin regulator Ezrin, which in turn positions the interphase centrosome in single epithelial cells and three-dimensional organotypic cultures. In the absence of Merlin, ectopic cortical Ezrin yields mispositioned centrosomes, misoriented spindles, and aberrant epithelial architecture. Furthermore, in tumor cells with centrosome amplification, the failure to restrict cortical Ezrin abolishes centrosome clustering, yielding multipolar mitoses. These data uncover fundamental roles for Merlin/ERM proteins in spatiotemporally organizing the cell cortex and suggest that Merlin's role in restricting cortical Ezrin may contribute to tumorigenesis by disrupting cell polarity, spindle orientation, and, potentially, genome stability. C1 [Hebert, Alan M.; DuBoff, Brian; Casaletto, Jessica B.; Gladden, Andrew B.; McClatchey, Andrea I.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. [Hebert, Alan M.; DuBoff, Brian; Casaletto, Jessica B.; Gladden, Andrew B.; McClatchey, Andrea I.] Harvard Univ, Dept Pathol, Sch Med, Charlestown, MA 02129 USA. RP McClatchey, AI (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. EM mcclatch@helix.mgh.harvard.edu FU National Institutes of Health [R01GM087558, R01CA113733]; MGH Research Scholars Award FX We are grateful to Amity Manning, Nick Dyson, David Pellman, Spyros Artavanis-Tsakonas, and Othon Iliopoulos for thoughtful comments regarding this manuscript, and to members of the McClatchey laboratory for many fruitful discussions. We thank Sylvie Robine for Vil-CreERT2 transgenic mice, and Marco Giovannini for Nf2lox/lox mice. We thank Cyril Benes, Rick Fehon, Phil Hinds, Marianne James, Wayne Lencer, Ian Macara, and Helen Morrison for reagents. These studies were supported by National Institutes of Health Grants (R01GM087558 and R01CA113733) and an MGH Research Scholars Award to A.I.M. NR 66 TC 21 Z9 21 U1 1 U2 7 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD DEC 15 PY 2012 VL 26 IS 24 BP 2709 EP 2723 DI 10.1101/gad.194027.112 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 060KF UT WOS:000312775700006 PM 23249734 ER PT J AU Peterson, KA Nishi, Y Ma, WX Vedenko, A Shokri, L Zhang, XX McFarlane, M Baizabal, JM Junker, JP van Oudenaarden, A Mikkelsen, T Bernstein, BE Bailey, TL Bulyk, ML Wong, WH McMahon, AP AF Peterson, Kevin A. Nishi, Yuichi Ma, Wenxiu Vedenko, Anastasia Shokri, Leila Zhang, Xiaoxiao McFarlane, Matthew Baizabal, Jose-Manuel Junker, Jan Philipp van Oudenaarden, Alexander Mikkelsen, Tarjei Bernstein, Bradley E. Bailey, Timothy L. Bulyk, Martha L. Wong, Wing H. McMahon, Andrew P. TI Neural-specific Sox2 input and differential Gli-binding affinity provide context and positional information in Shh-directed neural patterning SO GENES & DEVELOPMENT LA English DT Article DE Shh; Gli; neural tube patterning; morphogen ID CENTRAL-NERVOUS-SYSTEM; EMBRYONIC STEM-CELLS; SONIC-HEDGEHOG; FLOOR PLATE; SPINAL-CORD; TRANSCRIPTION FACTORS; PROGENITOR IDENTITY; SIGNALING PATHWAY; REGULATORY LOGIC; DORSAL GRADIENT AB In the vertebrate neural tube, regional Sonic hedgehog (Shh) signaling invokes a time-and concentration-dependent induction of six different cell populations mediated through Gli transcriptional regulators. Elsewhere in the embryo, Shh/Gli responses invoke different tissue-appropriate regulatory programs. A genome-scale analysis of DNA binding by Gli1 and Sox2, a pan-neural determinant, identified a set of shared regulatory regions associated with key factors central to cell fate determination and neural tube patterning. Functional analysis in transgenic mice validates core enhancers for each of these factors and demonstrates the dual requirement for Gli1 and Sox2 inputs for neural enhancer activity. Furthermore, through an unbiased determination of Gli-binding site preferences and analysis of binding site variants in the developing mammalian CNS, we demonstrate that differential Gli-binding affinity underlies threshold-level activator responses to Shh input. In summary, our results highlight Sox2 input as a context-specific determinant of the neural-specific Shh response and differential Gli-binding site affinity as an important cis-regulatory property critical for interpreting Shh morphogen action in the mammalian neural tube. C1 [Peterson, Kevin A.; Nishi, Yuichi; Baizabal, Jose-Manuel; McMahon, Andrew P.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Ma, Wenxiu] Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA. [Vedenko, Anastasia; Shokri, Leila] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Bulyk, Martha L.] Harvard Univ, Sch Med, Div Hlth Sci & Technol, Harvard Massachusetts Inst Technol, Boston, MA 02115 USA. [Zhang, Xiaoxiao; McFarlane, Matthew] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Junker, Jan Philipp; van Oudenaarden, Alexander] MIT, Dept Phys & Biol, Cambridge, MA 02139 USA. [van Oudenaarden, Alexander] KNAW Royal Netherlands Acad Arts & Sci, Hubrecht Inst, NL-3584 CT Utrecht, Netherlands. [van Oudenaarden, Alexander] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands. [Mikkelsen, Tarjei] Harvard Massachusetts Inst Technol, Broad Inst, Cambridge, MA 02142 USA. [Mikkelsen, Tarjei; McMahon, Andrew P.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Bernstein, Bradley E.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. [Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Syst Biol & Canc Res, Boston, MA 02114 USA. [Bailey, Timothy L.] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia. [Bulyk, Martha L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Wong, Wing H.] Stanford Univ, Dept Stat, Stanford, CA 94305 USA. [Wong, Wing H.] Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA. RP McMahon, AP (reprint author), Univ So Calif, Keck Sch Med, Dept Stem Cell Biol & Regenerat Med, Eli & Edythe Broad CIRM Ctr Regenerat Med & Stem, Los Angeles, CA 90089 USA. EM amcmahon@med.usc.edu RI Mikkelsen, Tarjei/A-1306-2007; Junker, Jan Philipp/A-9754-2010 OI Mikkelsen, Tarjei/0000-0002-8133-3135; Junker, Jan Philipp/0000-0002-2826-8290 FU NIH [R01 HG003985, R01 RR021692-05, R01 HG003903, R01 HG005717, R37 NS033642]; NRSA post-doctoral fellowships [F32 GM090645, F32 GM087939]; training grant HSCI [T32 HL087735] FX We thank Zhenjuan Wang, Ying Chen, and Manfred Baetscher (Harvard Genome Manipulation Facility) for pronuclear injection; Steve Vokes (University of Texas, Austin) for advice on ChIP-seq; Yasushi Nakagawa (University of Minnesota) for Dbx1 antibody; Hiroshi Sasaki (RIKEN) for sharing the Foxa2 enhancer construct; James Briscoe (MRC) for Foxa2 cDNA; Johan Ericson (Karolinska) for sharing unpublished data; Diane Faria for technical assistance; and Alex Schier and Susan Mango for critical comments and helpful discussions. This work was supported by NIH grants R01 HG003985 (to M. L. B.), R01 RR021692-05 (to T. L. B.), R01 HG003903 (to W. H. W.), R01 HG005717 (to W. H. W.), and R37 NS033642 (to A. P. M); NRSA post-doctoral fellowships F32 GM090645 (to L. S.) and F32 GM087939 (to K. A. P); and training grant HSCI T32 HL087735 (to K.A.P.). NR 61 TC 60 Z9 60 U1 0 U2 22 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD DEC 15 PY 2012 VL 26 IS 24 BP 2802 EP 2816 DI 10.1101/gad.207142.112 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 060KF UT WOS:000312775700012 PM 23249739 ER PT J AU Machiela, MJ Lindstrom, S Allen, NE Haiman, CA Albanes, D Barricarte, A Berndt, SI Bueno-de-Mesquita, HB Chanock, S Gaziano, JM Gapstur, SM Giovannucci, E Henderson, BE Jacobs, EJ Kolonel, LN Krogh, V Ma, J Stampfer, MJ Stevens, VL Stram, DO Tjonneland, A Travis, R Willett, WC Hunter, DJ Le Marchand, L Kraft, P AF Machiela, Mitchell J. Lindstroem, Sara Allen, Naomi E. Haiman, Christopher A. Albanes, Demetrius Barricarte, Aurelio Berndt, Sonja I. Bueno-de-Mesquita, H. Bas Chanock, Stephen Gaziano, J. Michael Gapstur, Susan M. Giovannucci, Edward Henderson, Brian E. Jacobs, Eric J. Kolonel, Laurence N. Krogh, Vittorio Ma, Jing Stampfer, Meir J. Stevens, Victoria L. Stram, Daniel O. Tjonneland, Anne Travis, Ruth Willett, Walter C. Hunter, David J. Le Marchand, Loic Kraft, Peter TI Association of Type 2 Diabetes Susceptibility Variants With Advanced Prostate Cancer Risk in the Breast and Prostate Cancer Cohort Consortium SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE carcinoma; diabetes mellitus; type 2; genetic predisposition to disease; genetics; genome-wide association study; humans; polymorphism; single nucleotide; prostatic neoplasms ID GENOME-WIDE ASSOCIATION; BASE-LINE CHARACTERISTICS; LARGE-SCALE ASSOCIATION; MULTIETHNIC COHORT; COMMON VARIANTS; LOCI; MELLITUS; GENES; METAANALYSIS; IDENTIFICATION AB Observational studies have found an inverse association between type 2 diabetes (T2D) and prostate cancer (PCa), and genome-wide association studies have found common variants near 3 loci associated with both diseases. The authors examined whether a genetic background that favors T2D is associated with risk of advanced PCa. Data from the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium, a genome-wide association study of 2,782 advanced PCa cases and 4,458 controls, were used to evaluate whether individual single nucleotide polymorphisms or aggregations of these 36 T2D susceptibility loci are associated with PCa. Ten T2D markers near 9 loci (NOTCH2, ADCY5, JAZF1, CDKN2A/B, TCF7L2, KCNQ1, MTNR1B, FTO, and HNF1B) were nominally associated with PCa (P < 0.05); the association for single nucleotide polymorphism rs757210 at the HNF1B locus was significant when multiple comparisons were accounted for (adjusted P = 0.001). Genetic risk scores weighted by the T2D log odds ratio and multilocus kernel tests also indicated a significant relation between T2D variants and PCa risk. A mediation analysis of 9,065 PCa cases and 9,526 controls failed to produce evidence that diabetes mediates the association of the HNF1B locus with PCa risk. These data suggest a shared genetic component between T2D and PCa and add to the evidence for an interrelation between these diseases. C1 [Machiela, Mitchell J.; Lindstroem, Sara; Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Allen, Naomi E.; Travis, Ruth] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England. [Haiman, Christopher A.; Henderson, Brian E.; Stram, Daniel O.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Albanes, Demetrius; Berndt, Sonja I.; Chanock, Stephen] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Barricarte, Aurelio] Navarre Publ Hlth Inst, Pamplona, Spain. [Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands. [Bueno-de-Mesquita, H. Bas] Univ Med Ctr Utrecht, Dept Gastroenterol & Hepatol, Utrecht, Netherlands. [Gaziano, J. Michael] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Gapstur, Susan M.; Jacobs, Eric J.; Stevens, Victoria L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Giovannucci, Edward; Stampfer, Meir J.; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA. [Krogh, Vittorio] Ist Nazl Tumori, Fdn IRCCS Ist Ricovero & Cura Carattere Sci, I-20133 Milan, Italy. [Ma, Jing; Stampfer, Meir J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Ma, Jing; Stampfer, Meir J.] Harvard Univ, Sch Med, Boston, MA USA. [Tjonneland, Anne] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. RP Kraft, P (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, 655 Huntington Ave,Bldg 2,Room 207, Boston, MA 02115 USA. EM pkraft@hsph.harvard.edu RI Machiela, Mitchell/F-9781-2013; Albanes, Demetrius/B-9749-2015; Krogh, Vittorio/K-2628-2016 OI Machiela, Mitchell/0000-0001-6538-9705; Krogh, Vittorio/0000-0003-0122-8624 FU National Cancer Institute [U01-CA98233-07, U01-CA98710-06, U01-CA98216-06, U01-CA98758-07]; Intramural Research Program of the National Institutes of Health/National Cancer Institute, Division of Cancer Epidemiology and Genetics; National Institutes of Health [T32-CA09001, T32-GM074897] FX This work was supported by the National Cancer Institute (cooperative agreements U01-CA98233-07 with David J. Hunter, U01-CA98710-06 with Susan M. Gapstur, U01-CA98216-06 with Elio Riboli and Rudolf Kaaks, and U01-CA98758-07 with Brian E. Henderson and the Intramural Research Program of the National Institutes of Health/National Cancer Institute, Division of Cancer Epidemiology and Genetics), as well as National Institutes of Health grants T32-CA09001 and T32-GM074897. NR 54 TC 24 Z9 25 U1 1 U2 17 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 15 PY 2012 VL 176 IS 12 BP 1121 EP 1129 DI 10.1093/aje/kws191 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 058LI UT WOS:000312634900008 PM 23193118 ER PT J AU Mai, XM Langhammer, A Camargo, CA Chen, Y AF Mai, Xiao-Mei Langhammer, Arnulf Camargo, Carlos A., Jr. Chen, Yue TI Serum 25-Hydroxyvitamin D Levels and Incident Asthma in Adults SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE allergic rhinitis; allergy; incident asthma; nested case-control study; prospective study; serum 25(OH)D; vitamin D ID VITAMIN-D INTAKE; NUTRITION EXAMINATION SURVEY; RESPIRATORY-TRACT INFECTION; NATIONAL-HEALTH; D DEFICIENCY; PREGNANCY; CHILDREN; ATOPY; WHEEZE; ASSOCIATION AB The impact of low vitamin D status on asthma development is unclear. The authors investigated the relation between the baseline serum 25-hydroxyvitamin D (25(OH)D) level and incident asthma in adults, including possible effect modification by allergy status, using allergic rhinitis as a proxy measure. A cohort of 25,616 Norwegian adults aged 1955 years participated in 2 surveys of the Nord-Trndelag Health Study known as HUNT 2 (19951997) and HUNT 3 (20062008). Of this cohort, a nested case-control study included 584 new-onset asthma cases and 1,958 nonasthma controls whose baseline serum 25(OH)D levels were measured. After adjustment for potential asthma risk factors, the baseline serum level of 25(OH)D (50 nmol/L) was not significantly associated with asthma in either women (adjusted odds ratio 0.94, 95 confidence interval (CI): 0.67, 1.32) or men (adjusted odds ratio 1.47, 95 CI: 0.93, 2.32). In men, allergic rhinitis modified the association with the adjusted odds ratio being 0.87 (95 CI: 0.36, 2.06) among men with allergic rhinitis and 2.32 (95 CI: 1.06, 5.10) among men without allergic rhinitis. The serum 25(OH)D level was not associated with incident asthma in women, regardless of allergy status. Low vitamin D status was not significantly associated with incident asthma in most adults, but it may have increased risk among men without allergy. C1 [Mai, Xiao-Mei; Langhammer, Arnulf] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, Fac Med, NO-7491 Trondheim, Norway. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Chen, Yue] Univ Ottawa, Fac Med, Dept Epidemiol & Community Med, Ottawa, ON, Canada. RP Mai, XM (reprint author), Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, Fac Med, NO-7491 Trondheim, Norway. EM xiao-mei.mai@ntnu.no RI Osborne, Nicholas/N-4915-2015 OI Osborne, Nicholas/0000-0002-6700-2284 FU Research Council of Norway [201895/V50]; AstraZeneca Norway FX This study was supported by the Research Council of Norway (project no. 201895/V50). The Lung Study in HUNT 2 and HUNT 3 received funding without obligation from AstraZeneca Norway. NR 34 TC 17 Z9 17 U1 0 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 15 PY 2012 VL 176 IS 12 BP 1169 EP 1176 DI 10.1093/aje/kws235 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 058LI UT WOS:000312634900013 PM 23204497 ER PT J AU Beck, S Bernstein, BE Campbell, RM Costello, JF Dhanak, D Ecker, JR Greally, JM Issa, JP Laird, PW Polyak, K Tycko, B Jones, PA AF Beck, Stephan Bernstein, Bradley E. Campbell, Robert M. Costello, Joseph F. Dhanak, Dashyant Ecker, Joseph R. Greally, John M. Issa, Jean-Pierre Laird, Peter W. Polyak, Kornelia Tycko, Benjamin Jones, Peter A. CA AACR Canc Epigenome Task Force TI A Blueprint for an International Cancer Epigenome Consortium. A Report from the AACR Cancer Epigenome Task Force SO CANCER RESEARCH LA English DT Editorial Material C1 [Beck, Stephan] UCL, Res Dept Canc Biol, Inst Canc, London, England. [Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Polyak, Kornelia] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Costello, Joseph F.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA. [Campbell, Robert M.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Ecker, Joseph R.] Salk Inst Biol Sci, Genom Anal Lab, La Jolla, CA USA. [Laird, Peter W.] Univ So Calif, Keck Sch Med, Dept Surg Biochem & Mol Biol, USC Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Jones, Peter A.] Univ So Calif, Keck Sch Med, Dept Urol, USC Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Jones, Peter A.] Univ So Calif, Keck Sch Med, Dept Biochem & Mol Biol, USC Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Dhanak, Dashyant] GlaxoSmithKline NI, Collegeville, PA USA. [Issa, Jean-Pierre] Temple Univ, Dept Med, Fels Inst Canc Res & Mol Biol, Sch Med, Philadelphia, PA 19122 USA. [Greally, John M.] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10467 USA. [Greally, John M.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Greally, John M.] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA. [Tycko, Benjamin] Columbia Univ, Dept Pathol, New York, NY USA. [Tycko, Benjamin] Columbia Univ, Dept Cell Biol, New York, NY USA. RP Beck, S (reprint author), UCL, Res Dept Canc Biol, Inst Canc, London, England. RI Ecker, Joseph/B-9144-2008; Stunnenberg, Hendrik/D-6875-2012; Laird, Peter/G-8683-2012; Esteller, Manel/L-5956-2014; Clark, Susan/B-2272-2008; OI Ecker, Joseph/0000-0001-5799-5895; Esteller, Manel/0000-0003-4490-6093; Clark, Susan/0000-0001-5925-5030; Helin, Kristian/0000-0003-1975-6097 FU NCI NIH HHS [R37 CA082422] NR 3 TC 12 Z9 12 U1 1 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 IS 24 BP 6319 EP 6324 DI 10.1158/0008-5472.CAN-12-3658 PG 6 WC Oncology SC Oncology GA 057VJ UT WOS:000312591900001 PM 23188507 ER PT J AU Feng, Y Wang, Y Wang, ZY Fang, ZY Li, F Gao, YJ Liu, HY Xiao, T Li, FM Zhou, Y Zhai, QW Liu, XL Sun, YH Bardeesy, N Wong, KK Chen, HQ Xiong, ZQ Ji, HB AF Feng, Yan Wang, Ye Wang, Zuoyun Fang, Zhaoyuan Li, Fei Gao, Yijun Liu, Hongyan Xiao, Tian Li, Fuming Zhou, Yang Zhai, Qiwei Liu, Xiaolong Sun, Yihua Bardeesy, Nabeel Wong, Kwok-kin Chen, Haiquan Xiong, Zhi-qi Ji, Hongbin TI The CRTC1-NEDD9 Signaling Axis Mediates Lung Cancer Progression Caused by LKB1 Loss SO CANCER RESEARCH LA English DT Article ID CREB COACTIVATOR TORC2; CARCINOMA-CELLS; FILAMENTATION 1; HUMAN ENHANCER; PROTEIN; KINASE; METASTASIS; EXPRESSION; MUTATIONS; GENE AB Somatic mutation of the tumor suppressor gene LKB1 occurs frequently in lung cancer where it causes tumor progression and metastasis, but the underlying mechanisms remain mainly unknown. Here, we show that the oncogene NEDD9 is an important downstream mediator of lung cancer progression evoked by LKB1 loss. In de novo mouse models, RNAi-mediated silencing of Nedd9 inhibited lung tumor progression, whereas ectopic NEDD9 expression accelerated this process. Mechanistically, LKB1 negatively regulated NEDD9 transcription by promoting cytosolic translocation of CRTC1 from the nucleus. Notably, ectopic expression of either NEDD9 or CRTC1 partially reversed the inhibitory function of LKB1 on metastasis of lung cancer cells. In clinical specimens, elevated expression of NEDD9 was associated with malignant progression and metastasis. Collectively, our results decipher the mechanism through which LKB1 deficiency promotes lung cancer progression and metastasis, and provide a mechanistic rationale for therapeutic attack of these processes. Cancer Res; 72(24); 6502-11. (c) 2012 AACR. C1 [Feng, Yan; Wang, Ye; Wang, Zuoyun; Fang, Zhaoyuan; Li, Fei; Gao, Yijun; Liu, Hongyan; Xiao, Tian; Li, Fuming; Liu, Xiaolong; Ji, Hongbin] Chinese Acad Sci, State Key Lab Cell Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China. [Zhou, Yang; Xiong, Zhi-qi] Chinese Acad Sci, Inst Neurosci, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China. [Zhou, Yang; Xiong, Zhi-qi] Chinese Acad Sci, State Key Lab Neurosci, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China. [Zhai, Qiwei] Chinese Acad Sci, Key Lab Nutr & Metab, Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai 200031, Peoples R China. [Sun, Yihua; Chen, Haiquan] Fudan Univ, Dept Thorac Surg, Shanghai Canc Ctr, Shanghai 200433, Peoples R China. [Sun, Yihua; Chen, Haiquan] Fudan Univ, Dept Oncol, Shanghai Med Coll, Shanghai 200433, Peoples R China. [Bardeesy, Nabeel] Massachusetts Gen Hosp, Dept Med, Ctr Canc, Boston, MA 02114 USA. [Wong, Kwok-kin] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Ji, HB (reprint author), Chinese Acad Sci, State Key Lab Cell Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, 320 Yue Yang Rd, Shanghai 200031, Peoples R China. EM hbji@sibs.ac.cn OI wong, kwok kin/0000-0001-6323-235X FU AstraZenca; Millenium; National Basic Research Program of China [2010CB912102, 2012CB910800]; National Natural Science Foundation of China [81101583, 30971461]; postdoctoral foundation [2010KIP504, 2011KIP505]; Shanghai postdoctoral foundation [Y15CS11371, Y149S11371] FX K.-K. Wong has a commercial research grant from AstraZenca and Millenium, and is a consultant/advisory board member of Molecular MD. No potential conflicts of interest were disclosed by the other authors.; This work was supported by the National Basic Research Program of China (2010CB912102; 2012CB910800), the National Natural Science Foundation of China (81101583 and 30971461). T. Xiao was supported by the postdoctoral foundation (2010KIP504) and Shanghai postdoctoral foundation (Y15CS11371 and Y149S11371). F. Li was supported by the postdoctoral foundation (2011KIP505). NR 46 TC 21 Z9 23 U1 1 U2 16 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 DEC 15 PY 2012 VL 72 IS 24 BP 6502 EP 6511 DI 10.1158/0008-5472.CAN-12-1909 PG 10 WC Oncology SC Oncology GA 057VJ UT WOS:000312591900020 PM 23074285 ER PT J AU Chen, DS Irving, BA Hodi, FS AF Chen, Daniel S. Irving, Bryan A. Hodi, F. Stephen TI Molecular Pathways: Next-Generation Immunotherapy-Inhibiting Programmed Death-Ligand 1 and Programmed Death-1 SO CLINICAL CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; T-CELLS; B7-H1 PD-L1; CLINICAL-SIGNIFICANCE; HEPATOCELLULAR-CARCINOMA; CANCER-IMMUNOTHERAPY; POTENTIAL MECHANISM; PROGNOSTIC-FACTORS; IMMUNE EVASION AB The aim of T-cell-based immune therapy for cancer has been to generate durable clinical benefit for patients. Following a generation of therapies that largely showed minimal activity, substantial toxicity, and no biomarkers to identify which patients benefit from treatment, early studies are showing signs that programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1) inhibitors are highly active. Preclinical and early data from clinical studies suggest that targeting this pathway can induce durable clinical responses in patients in a variety of tumor types, including lung and colon cancer. Furthermore, correlations with tumor PD-L1 expression may enable selection of patients most likely to benefit from treatment. The emerging data not only offer the hope of better cancer therapy but also provide evidence that changes our understanding of how the host immune system interacts with human cancer. Clin Cancer Res; 18(24); 6580-7. (C)2012 AACR. C1 [Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Chen, Daniel S.] Stanford Med Oncol, Stanford, CA USA. [Chen, Daniel S.; Irving, Bryan A.] Genentech Inc, San Francisco, CA 94080 USA. RP Hodi, FS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM stephen_hodi@dfci.harvard.edu NR 80 TC 85 Z9 92 U1 1 U2 25 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2012 VL 18 IS 24 BP 6580 EP 6587 DI 10.1158/1078-0432.CCR-12-1362 PG 8 WC Oncology SC Oncology GA 057RC UT WOS:000312580600003 PM 23087408 ER PT J AU Roccaro, AM Sacco, A Jia, XJ Banwait, R Maiso, P Azab, F Flores, L Manier, S Azab, AK Ghobrial, IM AF Roccaro, Aldo M. Sacco, Antonio Jia, Xiaojing Banwait, Ranjit Maiso, Patricia Azab, Feda Flores, Ludmila Manier, Salomon Azab, Abdel Kareem Ghobrial, Irene M. TI Mechanisms of Activity of the TORC1 Inhibitor Everolimus in Waldenstrom Macroglobulinemia SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL-CYCLE PROGRESSION; MULTIPLE-MYELOMA; SIGNALING PATHWAY; GROWTH; CANCER; TARGET; MTOR; PROLIFERATION; EXPRESSION; LYMPHOMAS AB Purpose: The TORC1 inhibitor everolimus has previously shown significant activity as a single agent in hematologic malignancies, with reported responses of 30% to 70% in Waldenstrom macroglobulinemia. However, the specific mechanisms by which this class of mTOR inhibitors exerts anti-Waldenstrom macroglobulinemia activity have not been fully investigated. We therefore sought to dissect the mechanisms of everolimus-dependent modulation of Waldenstrom macroglobulinemia cell survival. Experimental Design: We confirmed that everolimus targets mTOR in patients treated with everolimus and responding to therapy. We evaluated the effect of everolimus on proliferation and survival of primary Waldenstrom macroglobulinemia cells, as well as of other IgM-secreting lymphoma cell lines. Everolimus-dependent mechanisms of induced apoptosis and its effect on Waldenstrom macroglobulinemia cells in the context of bone marrow microenvironment have been also evaluated. miRNA-155 loss-of-function studies were conducted. Moreover, the combinatory effect of bortezomib and rituximab has been tested. Results: We showed that everolimus targeted mTOR downstream signaling pathways, ex vivo, in patients responding to everolimus treatment. Everolimus induced toxicity in primary Waldenstrom macroglobulinemia cells, as well as in other IgM-secreting lymphoma cells, supported by cell-cycle arrest and caspase-dependent and -independent induction of apoptosis. Importantly, everolimus targeted Waldenstrom macroglobulinemia cells even in the context of bone marrow milieu, where it affected migration, adhesion, and angiogenesis. Everolimus-dependent anti-Waldenstrom macroglobulinemia activity was partially driven by miRNA-155. Moreover, everolimus synergized with bortezomib and rituximab in targeting Waldenstrom macroglobulinemia cells, as shown by synergistic inhibition of p65/ and p50/NF-kB activities. Conclusions: These findings provide a better understanding of the mechanisms that are responsible for everolimus-induced anti-Waldenstrom macroglobulinemia activity. Clin Cancer Res; 18( 24); 6609-22. (C) 2012 AACR. C1 [Roccaro, Aldo M.; Sacco, Antonio; Jia, Xiaojing; Banwait, Ranjit; Maiso, Patricia; Azab, Feda; Flores, Ludmila; Manier, Salomon; Azab, Abdel Kareem; Ghobrial, Irene M.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Ghobrial, IM (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, 450 Brookline Av,HIM 247, Boston, MA 02215 USA. EM irene_ghobrial@dfci.harvard.edu RI Sacco, Antonio/K-4681-2016; OI Sacco, Antonio/0000-0003-2945-9416; Maiso, Patricia/0000-0003-3745-1924; Roccaro, Aldo/0000-0002-1872-5128 FU Heje fellowship for Waldenstrom; International Waldenstrom's Macroglobulinemia Foundation (IWMF); Michelle and Steven Kirsch lab for Waldenstrom; Accademia Nazionale dei Lincei; [1R01F0003743] FX The study was supported, in part, by 1R01F0003743, the Heje fellowship for Waldenstrom; the International Waldenstrom's Macroglobulinemia Foundation (IWMF); the Michelle and Steven Kirsch lab for Waldenstrom; the Heje fellowship for Waldenstrom; and the "Accademia Nazionale dei Lincei." NR 30 TC 5 Z9 5 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2012 VL 18 IS 24 BP 6609 EP 6622 DI 10.1158/1078-0432.CCR-12-1532 PG 14 WC Oncology SC Oncology GA 057RC UT WOS:000312580600006 PM 23048077 ER PT J AU Shao, L Tekedereli, I Wang, J Yuca, E Tsang, S Sood, A Lopez-Berestein, G Ozpolat, B Ittmann, M AF Shao, Longjiang Tekedereli, Ibrahim Wang, Jianghua Yuca, Erkan Tsang, Susan Sood, Anil Lopez-Berestein, Gabriel Ozpolat, Bulent Ittmann, Michael TI Highly Specific Targeting of the TMPRSS2/ERG Fusion Gene Using Liposomal Nanovectors SO CLINICAL CANCER RESEARCH LA English DT Article ID PROSTATE-CANCER PROGRESSION; INTERFERING RNA DELIVERY; IN-VIVO; TMPRSS2-ERG FUSION; MAMMALIAN-CELLS; TRANSCRIPTS; EXPRESSION; ACTIVATION AB Purpose: The TMPRSS2/ERG (T/E) fusion gene is present in half of all prostate cancer tumors. Fusion of the oncogenic ERG gene with the androgen-regulated TMPRSS2 gene promoter results in expression of fusion mRNAs in prostate cancer cells. The junction of the TMPRSS2- and ERG-derived portions of the fusion mRNA constitutes a cancer-specific target in cells containing the T/E fusion gene. Targeting the most common alternatively spliced fusion gene mRNA junctional isoforms in vivo using siRNAs in liposomal nanovectors may potentially be a novel, low-toxicity treatment for prostate cancer. Experimental Design: We designed and optimized siRNAs targeting the two most common T/E fusion gene mRNA junctional isoforms (type III or type VI). Specificity of siRNAs was assessed by transient co-transfection in vitro. To test their ability to inhibit growth of prostate cancer cells expressing these fusion gene isoforms in vivo, specific siRNAs in liposomal nanovectors were used to treat mice bearing orthotopic or subcutaneous xenograft tumors expressing the targeted fusion isoforms. Results: The targeting siRNAs were both potent and highly specific in vitro. In vivo they significantly inhibited tumor growth. The degree of growth inhibition was variable and was correlated with the extent of fusion gene knockdown. The growth inhibition was associated with marked inhibition of angiogenesis and, to a lesser degree, proliferation and a marked increase in apoptosis of tumor cells. No toxicity was observed. Conclusions: Targeting the T/E fusion junction in vivo with specific siRNAs delivered via liposomal nanovectors is a promising therapy for men with prostate cancer. Clin Cancer Res; 18(24); 6648-57. (C) 2012 AACR. C1 [Shao, Longjiang; Wang, Jianghua; Tsang, Susan; Ittmann, Michael] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Shao, Longjiang; Wang, Jianghua; Tsang, Susan; Ittmann, Michael] Baylor Coll Med, Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX 77030 USA. [Tekedereli, Ibrahim; Yuca, Erkan; Lopez-Berestein, Gabriel; Ozpolat, Bulent] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. [Sood, Anil] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX USA. RP Ittmann, M (reprint author), Baylor Coll Med, Dept Pathol & Immunol, 1 Baylor Plaza, Houston, TX 77030 USA. EM Bozpolat@mdanderson.org; mittmann@bcm.edu FU Department of Defense Prostate Cancer Research Program [W81XWH-09-1-038]; Prostate Cancer Foundation FX The study was supported by the Department of Defense Prostate Cancer Research Program (W81XWH-09-1-038; M. Ittmann and B. Ozpolat), the Prostate Cancer Foundation (M. Ittmann), and the use of the facilities of the Michael E. DeBakey VAMC. NR 30 TC 26 Z9 27 U1 2 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2012 VL 18 IS 24 BP 6648 EP 6657 DI 10.1158/1078-0432.CCR-12-2715 PG 10 WC Oncology SC Oncology GA 057RC UT WOS:000312580600009 PM 23052253 ER PT J AU Grupp, SA Prak, EL Boyer, J McDonald, KR Shusterman, S Thompson, E Callahan, C Jawad, AF Levine, BL June, CH Sullivan, KE AF Grupp, Stephan A. Prak, Eline Luning Boyer, Jean McDonald, Kenyetta R. Shusterman, Suzanne Thompson, Edward Callahan, Colleen Jawad, Abbas F. Levine, Bruce L. June, Carl H. Sullivan, Kathleen E. TI Adoptive Transfer of Autologous T Cells Improves T-cell Repertoire Diversity and Long-term B-cell Function in Pediatric Patients with Neuroblastoma SO CLINICAL CANCER RESEARCH LA English DT Article ID HIGH-RISK NEUROBLASTOMA; BONE-MARROW-TRANSPLANTATION; HIGH-DOSE THERAPY; INTENSIVE CHEMOTHERAPY; HOMEOSTATIC EXPANSION; PHENOTYPIC CONVERSION; MULTIPLE-MYELOMA; RAPID-SEQUENCE; IN-VIVO; CHILDREN AB Purpose: Children with high-risk neuroblastoma have a poor prognosis with chemotherapy alone, and hematopoietic stem cell transplantation offers improved survival. As a dose-escalation strategy, tandem transplants have been used, but are associated with persistent immunocompromise. This study evaluated the provision of an autologous costimulated, activated T-cell product to support immunologic function. Experimental Design: Nineteen subjects with high-risk neuroblastoma were enrolled in a pilot phase and 23 subjects were entered in to the randomized study. Immunologic reconstitution was defined by flow cytometric and functional assays. Next-generation sequencing was conducted to identify changes to the T-cell repertoire. Twenty-two patients were vaccinated to define effects on antibody responses. Results: Subjects who received their autologous costimulated T-cell product on day 2 had significantly superior T-cell counts and T-cell proliferation compared with those who received T cells on day 90. Early administration of autologous T cells suppressed oligoclonality and enhanced repertoire diversity. The subjects who received the day 2 T-cell product also had better responses to the pneumococcal vaccine. Conclusions: The infusion of activated T cells can improve immunologic function especially when given early after transplant. This study showed the benefit of providing cell therapies during periods of maximum lymphopenia. Clin Cancer Res; 18(24); 6732-41. (C) 2012 AACR. C1 [McDonald, Kenyetta R.; Sullivan, Kathleen E.] Childrens Hosp Philadelphia, Div Allergy Immunol, Philadelphia, PA 19104 USA. [Grupp, Stephan A.; Callahan, Colleen] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. [Jawad, Abbas F.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. [Prak, Eline Luning; Boyer, Jean; Thompson, Edward; Levine, Bruce L.; June, Carl H.] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Boyer, Jean; Thompson, Edward; Levine, Bruce L.; June, Carl H.] Univ Penn, Abramson Canc Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA. [Shusterman, Suzanne] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sullivan, KE (reprint author), Childrens Hosp Philadelphia, Div Allergy Immunol, 3615 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM sullivak@mail.med.upenn.edu OI Sullivan, Kathleen/0000-0003-4018-1646 FU NIH [NO1-AI-50 024, R01-CA105216] FX This work was supported in part by NIH NO1-AI-50 024 and R01-CA105216. NR 41 TC 17 Z9 19 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2012 VL 18 IS 24 BP 6732 EP 6741 DI 10.1158/1078-0432.CCR-12-1432 PG 10 WC Oncology SC Oncology GA 057RC UT WOS:000312580600017 PM 23092876 ER PT J AU Vos, T Flaxman, AD Naghavi, M Lozano, R Michaud, C Ezzati, M Shibuya, K Salomon, JA Abdalla, S Aboyans, V Abraham, J Ackerman, I Aggarwal, R Ahn, SY Ali, MK Alvarado, M Anderson, HR Anderson, LM Andrews, KG Atkinson, C Baddour, LM Bahalim, AN Barker-Collo, S Barrero, LH Bartels, DH Basanez, MG Baxter, A Bell, ML Benjamin, EJ Bennett, D Bernabe, E Bhalla, K Bhandari, B Bikbov, B Bin Abdulhak, A Birbeck, G Black, JA Blencowe, H Blore, JD Blyth, F Bolliger, I Bonaventure, A Boufous, SA Bourne, R Boussinesq, M Braithwaite, T Brayne, C Bridgett, L Brooker, S Brooks, P Brugha, TS Bryan-Hancock, C Bucello, C Buchbinder, R Buckle, GR Budke, CM Burch, M Burney, P Burstein, R Calabria, B Campbell, B Canter, CE Carabin, H Carapetis, J Carmona, L Cella, C Charlson, F Chen, HL Cheng, ATA Chou, D Chugh, SS Coffeng, LE Colan, SD Colquhoun, S Colson, KE Condon, J Connor, MD Cooper, LT Corriere, M Cortinovis, M de Vaccaro, KC Couser, W Cowie, BC Criqui, MH Cross, M Dabhadkar, KC Dahiya, M Dahodwala, N Damsere-Derry, J Danaei, G Davis, A De Leo, D Degenhardt, L Dellavalle, R Delossantos, A Denenberg, J Derrett, S Des Jarlais, DC Dharmaratne, SD Dherani, M Diaz-Torne, C Dolk, H Dorsey, ER Driscoll, T Duber, H Ebel, B Edmond, K Elbaz, A Ali, SE Erskine, H Erwin, PJ Espindola, P Ewoigbokhan, SE Farzadfar, F Feigin, V Felson, DT Ferrari, A Ferri, CP Fevre, EM Finucane, MM Flaxman, S Flood, L Foreman, K Forouzanfar, MH Fowkes, FGR Franklin, R Fransen, M Freeman, MK Gabbe, BJ Gabriel, SE Gakidou, E Ganatra, HA Garcia, B Gaspari, F Gillum, RF Gmel, G Gosselin, R Grainger, R Groeger, J Guillemin, F Gunnell, D Gupta, R Haagsma, J Hagan, H Halasa, YA Hall, W Haring, D Haro, JM Harrison, JE Havmoeller, R Hay, RJ Higashi, H Hill, C Hoen, B Hoffman, H Hotez, PJ Hoy, D Huang, JJ Ibeanusi, SE Jacobsen, KH James, SL Jarvis, D Jasrasaria, R Jayaraman, S Johns, N Jonas, JB Karthikeyan, G Kassebaum, N Kawakami, N Keren, A Khoo, JP King, CH Knowlton, LM Kobusingye, O Koranteng, A Krishnamurthi, R Lalloo, R Laslett, LL Lathlean, T Leasher, JL Lee, YY Leigh, J Lim, SS Limb, E Lin, JK Lipnick, M Lipshultz, SE Liu, W Loane, M Ohno, SL Lyons, R Ma, JX Mabweijano, J MacIntyre, MF Malekzadeh, R Mallinger, L Manivannan, S Marcenes, W March, L Margolis, DJ Marks, GB Marks, R Matsumori, A Matzopoulos, R Mayosi, BM McAnulty, JH McDermott, MM McGill, N McGrath, J Medina-Mora, ME Meltzer, M Mensah, GA Merriman, TR Meyer, AC Miglioli, V Miller, M Miller, TR Mitchell, PB Mocumbi, AO Moffitt, TE Mokdad, AA Monasta, L Montico, M Moradi-Lakeh, M Moran, A Morawska, L Mori, R Murdoch, ME Mwaniki, MK Naidoo, K Nair, MN Naldi, L Narayan, KMV Nelson, PK Nelson, RG Nevitt, MC Newton, CR Nolte, S Norman, P Norman, R O'Donnell, M O'Hanlon, S Olives, C Omer, SB Ortblad, K Osborne, R Ozgediz, D Page, A Pahari, B Pandian, JD Rivero, AP Patten, SB Pearce, N Padilla, RP Perez-Ruiz, F Perico, N Pesudovs, K Phillips, D Phillips, MR Pierce, K Pion, S Polanczyk, GV Polinder, S Pope, CA Popova, S Porrini, E Pourmalek, F Prince, M Pullan, RL Ramaiah, KD Ranganathan, D Razavi, H Regan, M Rehm, JT Rein, DB Remuzzi, G Richardson, K Rivara, FP Roberts, T Robinson, C De Leon, FR Ronfani, L Room, R Rosenfeld, LC Rushton, L Sacco, RL Saha, S Sampson, U Sanchez-Riera, L Sanman, E Schwebel, DC Scott, JG Segui-Gomez, M Shahraz, S Shepard, DS Shin, H Shivakoti, R Singh, D Singh, GM Singh, JA Singleton, J Sleet, DA Sliwa, K Smith, E Smith, JL Stapelberg, NJC Steer, A Steiner, T Stolk, WA Stovner, LJ Sudfeld, C Syed, S Tamburlini, G Tavakkoli, M Taylor, HR Taylor, JA Taylor, WJ Thomas, B Thomson, WM Thurston, GD Tleyjeh, IM Tonelli, M Towbin, JRA Truelsen, T Tsilimbaris, MK Ubeda, C Undurraga, EA van der Werf, MJ van Os, J Vavilala, MS Venketasubramanian, N Wang, MR Wang, WZ Watt, K Weatherall, DJ Weinstock, MA Weintraub, R Weisskopf, MG Weissman, MM White, RA Whiteford, H Wiersma, ST Wilkinson, JD Williams, HC Williams, SRM Witt, E Wolfe, F Woolf, AD Wulf, S Yeh, PH Zaidi, AKM Zheng, ZJ Zonies, D Lopez, AD Murray, CJL AF Vos, Theo Flaxman, Abraham D. Naghavi, Mohsen Lozano, Rafael Michaud, Catherine Ezzati, Majid Shibuya, Kenji Salomon, Joshua A. Abdalla, Safa Aboyans, Victor Abraham, Jerry Ackerman, Ilana Aggarwal, Rakesh Ahn, Stephanie Y. Ali, Mohammed K. Alvarado, Miriam Anderson, H. Ross Anderson, Laurie M. Andrews, Kathryn G. Atkinson, Charles Baddour, Larry M. Bahalim, Adil N. Barker-Collo, Suzanne Barrero, Lope H. Bartels, David H. Basanez, Maria-Gloria Baxter, Amanda Bell, Michelle L. Benjamin, Emelia J. Bennett, Derrick Bernabe, Eduardo Bhalla, Kavi Bhandari, Bishal Bikbov, Boris Bin Abdulhak, Aref Birbeck, Gretchen Black, James A. Blencowe, Hannah Blore, Jed D. Blyth, Fiona Bolliger, Ian Bonaventure, Audrey Boufous, Soufi Ane Bourne, Rupert Boussinesq, Michel Braithwaite, Tasanee Brayne, Carol Bridgett, Lisa Brooker, Simon Brooks, Peter Brugha, Traolach S. Bryan-Hancock, Claire Bucello, Chiara Buchbinder, Rachelle Buckle, Geoff Rey Budke, Christine M. Burch, Michael Burney, Peter Burstein, Roy Calabria, Bianca Campbell, Benjamin Canter, Charles E. Carabin, Helene Carapetis, Jonathan Carmona, Loreto Cella, Claudia Charlson, Fiona Chen, Honglei Cheng, Andrew Tai-Ann Chou, David Chugh, Sumeet S. Coffeng, Luc E. Colan, Steven D. Colquhoun, Samantha Colson, K. Ellicott Condon, John Connor, Myles D. Cooper, Leslie T. Corriere, Matthew Cortinovis, Monica de Vaccaro, Karen Courville Couser, William Cowie, Benjamin C. Criqui, Michael H. Cross, Marita Dabhadkar, Kaustubh C. Dahiya, Manu Dahodwala, Nabila Damsere-Derry, James Danaei, Goodarz Davis, Adrian De Leo, Diego Degenhardt, Louisa Dellavalle, Robert Delossantos, Allyne Denenberg, Julie Derrett, Sarah Des Jarlais, Don C. Dharmaratne, Samath D. Dherani, Mukesh Diaz-Torne, Cesar Dolk, Helen Dorsey, E. Ray Driscoll, Tim Duber, Herbert Ebel, Beth Edmond, Karen Elbaz, Alexis Ali, Suad Eltahir Erskine, Holly Erwin, Patricia J. Espindola, Patricia Ewoigbokhan, Stalin E. Farzadfar, Farshad Feigin, Valery Felson, David T. Ferrari, Alize Ferri, Cleusa P. Fevre, Eric M. Finucane, Mariel M. Flaxman, Seth Flood, Louise Foreman, Kyle Forouzanfar, Mohammad H. Fowkes, Francis Gerry R. Franklin, Richard Fransen, Marlene Freeman, Michael K. Gabbe, Belinda J. Gabriel, Sherine E. Gakidou, Emmanuela Ganatra, Hammad A. Garcia, Bianca Gaspari, Flavio Gillum, Richard F. Gmel, Gerhard Gosselin, Richard Grainger, Rebecca Groeger, Justina Guillemin, Francis Gunnell, David Gupta, Ramyani Haagsma, Juanita Hagan, Holly Halasa, Yara A. Hall, Wayne Haring, Diana Maria Haro, Josep Harrison, James E. Havmoeller, Rasmus Hay, Roderick J. Higashi, Hideki Hill, Catherine Hoen, Bruno Hoffman, Howard Hotez, Peter J. Hoy, Damian Huang, John J. Ibeanusi, Sydney E. Jacobsen, Kathryn H. James, Spencer L. Jarvis, Deborah Jasrasaria, Rashmi Jayaraman, Sudha Johns, Nicole Jonas, Jost B. Karthikeyan, Ganesan Kassebaum, Nicholas Kawakami, Norito Keren, Andre Khoo, Jon-Paul King, Charles H. Knowlton, Lisa Marie Kobusingye, Olive Koranteng, Adofo Krishnamurthi, Rita Lalloo, Ratilal Laslett, Laura L. Lathlean, Tim Leasher, Janet L. Lee, Yong Yi Leigh, James Lim, Stephen S. Limb, Elizabeth Lin, John Kent Lipnick, Michael Lipshultz, Steven E. Liu, Wei Loane, Maria Ohno, Summer Lockett Lyons, Ronan Ma, Jixiang Mabweijano, Jacqueline MacIntyre, Michael F. Malekzadeh, Reza Mallinger, Leslie Manivannan, Sivabalan Marcenes, Wagner March, Lyn Margolis, David J. Marks, Guy B. Marks, Robin Matsumori, Akira Matzopoulos, Richard Mayosi, Bongani M. McAnulty, John H. McDermott, Mary M. McGill, Neil McGrath, John Elena Medina-Mora, Maria Meltzer, Michele Mensah, George A. Merriman, Tony R. Meyer, Ana-Claire Miglioli, Valeria Miller, Matthew Miller, Ted R. Mitchell, Philip B. Mocumbi, Ana Olga Moffitt, Terrie E. Mokdad, Ali A. Monasta, Lorenzo Montico, Marcella Moradi-Lakeh, Maziar Moran, Andrew Morawska, Lidia Mori, Rintaro Murdoch, Michele E. Mwaniki, Michael K. Naidoo, Kovin Nair, M. Nathan Naldi, Luigi Narayan, K. M. Venkat Nelson, Paul K. Nelson, Robert G. Nevitt, Michael C. Newton, Charles R. Nolte, Sandra Norman, Paul Norman, Rosana O'Donnell, Martin O'Hanlon, Simon Olives, Casey Omer, Saad B. Ortblad, Katrina Osborne, Richard Ozgediz, Doruk Page, Andrew Pahari, Bishnu Pandian, Jeyaraj Durai Rivero, Andrea Panozo Patten, Scott B. Pearce, Neil Perez Padilla, Rogelio Perez-Ruiz, Fernando Perico, Norberto Pesudovs, Konrad Phillips, David Phillips, Michael R. Pierce, Kelsey Pion, Sebastien Polanczyk, Guilherme V. Polinder, Suzanne Pope, C. Arden, III Popova, Svetlana Porrini, Esteban Pourmalek, Farshad Prince, Martin Pullan, Rachel L. Ramaiah, Kapa D. Ranganathan, Dharani Razavi, Homie Regan, Mathilda Rehm, Juergen T. Rein, David B. Remuzzi, Guiseppe Richardson, Kathryn Rivara, Frederick P. Roberts, Thomas Robinson, Carolyn De Leon, Felipe Rodriguez Ronfani, Luca Room, Robin Rosenfeld, Lisa C. Rushton, Lesley Sacco, Ralph L. Saha, Sukanta Sampson, Uchechukwu Sanchez-Riera, Lidia Sanman, Ella Schwebel, David C. Scott, James Graham Segui-Gomez, Maria Shahraz, Saeid Shepard, Donald S. Shin, Hwashin Shivakoti, Rupak Singh, David Singh, Gitanjali M. Singh, Jasvinder A. Singleton, Jessica Sleet, David A. Sliwa, Karen Smith, Emma Smith, Jennifer L. Stapelberg, Nicolas J. C. Steer, Andrew Steiner, Timothy Stolk, Wilma A. Stovner, Lars Jacob Sudfeld, Christopher Syed, Sana Tamburlini, Giorgio Tavakkoli, Mohammad Taylor, Hugh R. Taylor, Jennifer A. Taylor, William J. Thomas, Bernadette Thomson, W. Murray Thurston, George D. Tleyjeh, Imad M. Tonelli, Marcello Towbin, Jeff Rey A. Truelsen, Thomas Tsilimbaris, Miltiadis K. Ubeda, Clotilde Undurraga, Eduardo A. van der Werf, Marieke J. van Os, Jim Vavilala, Monica S. Venketasubramanian, N. Wang, Mengru Wang, Wenzhi Watt, Kerrianne Weatherall, David J. Weinstock, Martin A. Weintraub, Robert Weisskopf, Marc G. Weissman, Myrna M. White, Richard A. Whiteford, Harvey Wiersma, Steven T. Wilkinson, James D. Williams, Hywel C. Williams, Sean R. M. Witt, Emma Wolfe, Frederick Woolf, Anthony D. Wulf, Sarah Yeh, Pon-Hsiu Zaidi, Anita K. M. Zheng, Zhi-Jie Zonies, David Lopez, Alan D. Murray, Christopher J. L. TI Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010 SO LANCET LA English DT Article ID NEGLECTED TROPICAL DISEASES; ADJUSTED-LIFE-YEARS; IRON-DEFICIENCY ANEMIA; DEVELOPING-COUNTRIES; ANCHORING VIGNETTES; DEPRESSIVE DISORDER; HEARING IMPAIRMENT; COGNITIVE FUNCTION; MENTAL-DISORDERS; RISK-FACTORS AB Background Non-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs). Methods Of the 291 diseases and injuries in the GBD cause list, 289 cause disability. For 1160 sequelae of the 289 diseases and injuries, we undertook a systematic analysis of prevalence, incidence, remission, duration, and excess mortality. Sources included published studies, case notification, population-based cancer registries, other disease registries, antenatal clinic serosurveillance, hospital discharge data, ambulatory care data, household surveys, other surveys, and cohort studies. For most sequelae, we used a Bayesian meta-regression method, DisMod-MR, designed to address key limitations in descriptive epidemiological data, including missing data, inconsistency, and large methodological variation between data sources. For some disorders, we used natural history models, geospatial models, back-calculation models (models calculating incidence from population mortality rates and case fatality), or registration completeness models (models adjusting for incomplete registration with health-system access and other covariates). Disability weights for 220 unique health states were used to capture the severity of health loss. YLDs by cause at age, sex, country, and year levels were adjusted for comorbidity with simulation methods. We included uncertainty estimates at all stages of the analysis. Findings Global prevalence for all ages combined in 2010 across the 1160 sequelae ranged from fewer than one case per 1 million people to 350 000 cases per 1 million people. Prevalence and severity of health loss were weakly correlated (correlation coefficient -0.37). In 2010, there were 777 million YLDs from all causes, up from 583 million in 1990. The main contributors to global YLDs were mental and behavioural disorders, musculoskeletal disorders, and diabetes or endocrine diseases. The leading specific causes of YLDs were much the same in 2010 as they were in 1990: low back pain, major depressive disorder, iron-deficiency anaemia, neck pain, chronic obstructive pulmonary disease, anxiety disorders, migraine, diabetes, and falls. Age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010. Regional patterns of the leading causes of YLDs were more similar compared with years of life lost due to premature mortality. Neglected tropical diseases, HIV/AIDS, tuberculosis, malaria, and anaemia were important causes of YLDs in sub-Saharan Africa. Interpretation Rates of YLDs per 100 000 people have remained largely constant over time but rise steadily with age. Population growth and ageing have increased YLD numbers and crude rates over the past two decades. Prevalences of the most common causes of YLDs, such as mental and behavioural disorders and musculoskeletal disorders, have not decreased. Health systems will need to address the needs of the rising numbers of individuals with a range of disorders that largely cause disability but not mortality. Quantification of the burden of non-fatal health outcomes will be crucial to understand how well health systems are responding to these challenges. Effective and affordable strategies to deal with this rising burden are an urgent priority for health systems in most parts of the world. C1 [Baxter, Amanda; Erskine, Holly; Ferrari, Alize; Khoo, Jon-Paul; Saha, Sukanta; Whiteford, Harvey] Univ Queensland, Queensland Ctr Mental Hlth Res, Brisbane, Qld, Australia. 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[Mori, Rintaro] Natl Ctr Child Hlth & Dev, Tokyo, Japan. [Murdoch, Michele E.] Watford Dist Gen Hosp, Watford, England. [Mwaniki, Michael K.] Kemri Wellcome Trust, Kilifi, Kenya. [Naidoo, Kovin] Univ KwaZulu Natal, AVRI, Durban, South Africa. [Naldi, Luigi] Ctr Studi GISED, Bergamo, Italy. [Nolte, Sandra] Charite, D-13353 Berlin, Germany. [O'Donnell, Martin] Natl Univ Ireland Galway, HRB Clin Res Facil, Galway, Ireland. [Osborne, Richard] Deakin Univ, Melbourne, Vic, Australia. [Pahari, Bishnu] BP Koirala Inst Hlth Sci, Dharan, Nepal. [Pandian, Jeyaraj Durai] Betty Cowan Res & Innovat Ctr, Ludhiana, Punjab, India. [Rivero, Andrea Panozo] Hosp Joan 23, La Paz, Bolivia. [Patten, Scott B.] Univ Calgary, Calgary, AB, Canada. [Perez Padilla, Rogelio] Inst Nacl Enfermedades Resp, Mexico City, DF, Mexico. [Perez-Ruiz, Fernando] Hosp Univ Cruces, Baracaldo, Spain. [Phillips, Michael R.] Shanghai Jiao Tong Univ, Sch Med, Shanghai Mental Hlth Ctr, Shanghai 200030, Peoples R China. [Zheng, Zhi-Jie] Shanghai Jiao Tong Univ, Sch Publ Hlth, Shanghai 200030, Peoples R China. [Pope, C. Arden, III] Brigham Young Univ, Provo, UT 84602 USA. [Popova, Svetlana; Rehm, Juergen T.] Ctr Addict & Mental Hlth, Toronto, ON, Canada. [Porrini, Esteban] Hosp Univ Canarias, Tenerif, Spain. [Pourmalek, Farshad] Univ British Columbia, Fac Med, Sch Populat & Publ Hlth, Vancouver, BC, Canada. [Ramaiah, Kapa D.] Vector Control Res Ctr, Pondicherry, India. [Razavi, Homie] Ctr Dis Anal, Louisville, CO USA. [Regan, Mathilda] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Rein, David B.] Univ Chicago, NORC, Chicago, IL 60637 USA. [De Leon, Felipe Rodriguez] Complejo Hosp Caja Seguro Social, Panama City, Panama. [Room, Robin] Turning Point Alcohol & Drug Ctr, Ctr Alcohol Policy Res, Fitzroy, SA, Australia. [Sampson, Uchechukwu] Vanderbilt Univ, Nashville, TN USA. [Schwebel, David C.; Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham, AL USA. [Segui-Gomez, Maria] Minist Interior, Madrid, Spain. [Shin, Hwashin] Hlth Canada, Ottawa, ON K1A 0L2, Canada. [Singh, David] Queens Med Ctr, Honolulu, HI USA. [Stovner, Lars Jacob] Norwegian Univ Sci & Technol, Dept Neurosci, N-7034 Trondheim, Norway. [Syed, Sana; Zaidi, Anita K. M.] Agwa Khan Univ, Karachi, Pakistan. [Taylor, Jennifer A.] Drexel Univ, Sch Publ Hlth, Philadelphia, PA 19104 USA. [Tonelli, Marcello] Univ Alberta, Alberta Kidney Dis Network, Edmonton, AB, Canada. [Towbin, Jeff Rey A.] Cincinnati Childrens Hosp, Cincinnati, OH USA. [Truelsen, Thomas] Copenhagen Univ Hosp, Dept Neurol, Herlev, Denmark. [Tsilimbaris, Miltiadis K.] Univ Crete, Sch Med, Iraklion, Greece. [Ubeda, Clotilde] ANLIS, Inst Nacl Epidemiol, Malbran, Argentina. [van der Werf, Marieke J.] KNCV TB Fdn, The Hague, Netherlands. [van Os, Jim] Maastricht Univ Med Ctr, Maastricht, Netherlands. [Venketasubramanian, N.] Natl Univ Singapore, Singapore 117548, Singapore. [Wang, Wenzhi] Capital Med Univ, Beijing Neurosurg Inst, Beijing, Peoples R China. [Weinstock, Martin A.] Brown Univ, Providence, RI 02912 USA. [Weintraub, Robert] Royal Childrens Hosp, Melbourne, Vic, Australia. [Weintraub, Robert] Murdoch Childrens Res Inst, Melbourne, Vic, Australia. [Williams, Hywel C.] Univ Nottingham, Nottingham NG7 2RD, England. [Williams, Sean R. M.] Univ Western Sydney, Campbelltown, NSW, Australia. [Wolfe, Frederick] Arthrit Res, Wichita, KS USA. [Woolf, Anthony D.] Royal Cornwall Hosp, Truro, England. [Yeh, Pon-Hsiu] London Sch Econ, London WC2A 2AE, England. [Zonies, David] Landstuhl Reg Med Ctr, Landstuhl, Germany. [Nelson, Robert G.] NIDDK, NIH, Bethesda, MD USA. RP Murray, CJL (reprint author), Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA. EM cjlm@uw.edu RI Undurraga, Eduardo/I-3739-2014; Higashi, Hideki/D-3797-2011; Bolliger, Ian/C-4207-2016; Boussinesq, Michel/J-7256-2016; Jacobsen, Kathryn/B-5857-2008; Naldi, Luigi/K-6343-2016; Lalloo, Ratilal/O-5624-2014; Scott, James/D-5900-2012; Salomon, Joshua/D-3898-2009; Franklin, Richard/H-1731-2012; Dellavalle, Robert/L-2020-2013; Baxter, Amanda/E-5449-2011; Research ID, CTBCC /O-3564-2014; Prince, Martin/A-9170-2010; Charlson, Fiona/F-5290-2011; Harrison, James/B-8958-2009; Whiteford, Harvey/A-4840-2009; Ferri, Cleusa/B-2922-2010; Tonelli, Marcello/B-3028-2009; Haro, Josep Maria/D-1423-2011; Carabin, Helene/B-7600-2016; Patten, Scott/B-4434-2011; Monasta, Lorenzo/B-1388-2012; Stovner, Lars/D-5025-2014; Moffitt, Terrie/D-5295-2011; Ebel, Beth/F-4544-2014; Lopez, Alan/F-1487-2010; Laslett, Laura/G-3973-2011; Narayan, K.M. Venkat /J-9819-2012; Hall, Wayne/A-3283-2008; Ronfani, Luca/B-6668-2013; Nolte, Sandra/B-7498-2008; Bikbov, Boris/I-4594-2013; Lee, Yong Yi/C-1373-2015; Carmona, Loreto/A-2748-2014; Saha, Sukanta/K-3774-2012; McGrath, John/G-5493-2010; Montico, Marcella/B-5290-2013; Black, James/A-5917-2010; Erskine, Holly/K-5244-2012; NORMAN, ROSANA/F-2774-2010; Buchbinder, Rachelle/G-2952-2011; Polanczyk, Guilherme/C-2345-2012; Jarvis, Deborah/E-6494-2011; Degenhardt, Louisa/D-4515-2012; Norman, Paul/C-5485-2013; Lathlean, Tim/K-3653-2013 OI Phillips, David/0000-0003-2569-1015; Johns, Nicole/0000-0003-4513-4582; Benjamin, Emelia/0000-0003-4076-2336; Newton, Charles/0000-0002-6999-5507; Leasher, Janet/0000-0002-8779-5162; Weissman, Myrna/0000-0003-3490-3075; Mitchell, Philip/0000-0002-7954-5235; Aggarwal, Rakesh/0000-0001-9689-494X; Mock, Charles/0000-0002-0564-568X; Loane, Maria/0000-0002-1206-3637; Undurraga, Eduardo/0000-0002-4425-1253; Cowie, Benjamin/0000-0002-7087-5895; O'Donnell, Martin/0000-0002-7347-7761; O'donnell, Colm/0000-0002-8004-450X; Malekzadeh, Reza/0000-0003-1043-3814; singh, jasvinder/0000-0003-3485-0006; Mensah, George/0000-0002-0387-5326; Higashi, Hideki/0000-0002-5534-0905; Bolliger, Ian/0000-0001-8055-297X; Boussinesq, Michel/0000-0001-6312-0681; Jacobsen, Kathryn/0000-0002-4198-6246; Naldi, Luigi/0000-0002-3160-2835; Lalloo, Ratilal/0000-0001-5822-1269; Scott, James/0000-0002-0744-0688; Salomon, Joshua/0000-0003-3929-5515; Franklin, Richard/0000-0003-1864-4552; Dellavalle, Robert/0000-0001-8132-088X; Hotez, Peter/0000-0001-8770-1042; Ebel, Beth/0000-0001-9310-8325; Baxter, Amanda/0000-0001-8198-9022; Prince, Martin/0000-0003-1379-7146; Charlson, Fiona/0000-0003-2876-5040; Harrison, James/0000-0001-9893-8491; Whiteford, Harvey/0000-0003-4667-6623; Ferri, Cleusa/0000-0002-1815-7685; Haro, Josep Maria/0000-0002-3984-277X; Patten, Scott/0000-0001-9871-4041; Monasta, Lorenzo/0000-0001-7774-548X; Chen, Honglei/0000-0003-3446-7779; Perez-Ruiz, Fernando/0000-0002-5268-1894; King, Charles/0000-0001-8349-9270; Osborne, Richard/0000-0002-9081-2699; Bernabe, Eduardo/0000-0002-1858-3713; Moradi-Lakeh, Maziar/0000-0001-7381-5305; Mayosi, Bongani/0000-0001-6641-8950; Gabbe, Belinda/0000-0001-7096-7688; Cella, Claudia/0000-0002-9210-0775; Taylor, Hugh/0000-0002-9437-784X; Erskine, Holly/0000-0003-3119-9211; Aboyans, Victor/0000-0002-0322-9818; Merriman, Tony/0000-0003-0844-8726; Razavi, Homie/0000-0002-2658-6930; Pourmalek, Farshad/0000-0002-2134-0771; Miller, Ted/0000-0002-0958-2639; Cesar, Diaz-Torne/0000-0001-6275-7699; Fevre, Eric/0000-0001-8931-4986; Pesudovs, Konrad/0000-0002-6322-9369; Moffitt, Terrie/0000-0002-8589-6760; Lopez, Alan/0000-0001-5818-6512; Laslett, Laura/0000-0002-4336-0095; Narayan, K.M. Venkat /0000-0001-8621-5405; Hall, Wayne/0000-0003-1984-0096; Ronfani, Luca/0000-0001-5710-3914; Nolte, Sandra/0000-0001-6185-9423; Bikbov, Boris/0000-0002-1925-7506; Lee, Yong Yi/0000-0003-2359-6823; Carmona, Loreto/0000-0002-4401-2551; McGrath, John/0000-0002-4792-6068; Montico, Marcella/0000-0003-0377-8232; Black, James/0000-0002-2200-3179; NORMAN, ROSANA/0000-0002-9742-1957; Polanczyk, Guilherme/0000-0003-2311-3289; Degenhardt, Louisa/0000-0002-8513-2218; Norman, Paul/0000-0003-3406-0506; FU Berlin Heart Honoraria; Lundbeck; Medtronic; Prana Biotechnology; Safework Australia; Assurance-Maladie (CNAMTS) InVS; Inserm; CHU de Nancy; CHU de Nice; Conseil Regional de Lorraine; Societe Francaise de Negma-Lerads; Pfizer; Pierre Fabre Medicaments; Sanofi-Aventis France; Spanish Health Ministry; Hospital de Cruces Rheumatology Association; Novartis; National Council for Scientific and Technological Development (CNPq, Brazil); European Chemical Industry Council (CEFIC); CONCAWE (Conservation of Clean Air and Water Europe); Takeda; Savient; Ardea; Regeneron; Allergan; URL pharmaceuticals; 36 companies; National Institutes of Arthritis, Musculoskeletal and Skin Diseases (NIAMS); National Institute on Aging (NIA); National Cancer Institute (NCI); Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs); Moscow State University of Medicine and Dentistry, Moscow, Russia; Academician V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs, Moscow, Russia; International Society of Nephrology; Wellcome Trust [098045, 085308]; Department of Health London for the National Health Service Information Centre; University of Leicester; Australian National Health and Medical Research Council (NHMRC); Monash University; Cabrini Health; BUPA Foundation; NIH, the National Institute of Environmental Health Sciences; Africa Programme for Onchocerciasis Control (WHO/APOC); NIH [K23 AG034236]; Parkinson Council; Australian NHMRC; US Department of Veterans Affairs; Health Research Council of New Zealand; University of Otago; National Institute for Stroke and Applied Neurosciences; Swedish Research Council [2011-1071]; Bill and Melinda Gates Foundation; Australian National Health and Medical Research Council; World Health Organization; World Mental Health Japan (WMH-J); Grant for Research on Psychiatric and Neurological Diseases and Mental Health from the Japan Ministry of Health, Labour, and Welfare [H13-SHOGAI-023, H14-TOKUBETSU-026, H16-KOKORO-013]; Australian Government; National Health and Medical Research Council of Australia; Arthritis Foundation of Australia; Tasmanian Community Fund; Masonic Centenary Medical Research Foundation; Royal Hobart Hospital Research Foundation; University of Tasmania; Tehran University of Medical Sciences; South African Medical Research Council Burden of Disease Research Unit; University of Cape Town School of Public Health and Family Medicine; Brien Holden Vision Institute; National Drug and Alcohol Research Centre (UNSW, Australia); Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases; Biostatistics, Epidemiologic and Bioinformatic Training in Environmental Health Training Grant [ES015459]; Burke Global Health Fellowship; Harold Amos Medical Faculty Development Award of the Robert Wood Johnson Foundation; Vanderbilt Clinical and Translational Scholars Award; European Center for Injury Prevention, Universidad de Navarra; National Institute of Environmental Health Sciences [ES00260]; Wellcome Trust UK; Medical Research Council UK; Anthony Cerami and Ann Dunne Research Trust; AUT University FX C E Canter has worked as an Optum Health consultant, Blue Cross Blue Shield consultant, and received Berlin Heart Honoraria and travel fees. E R Dorsey has received payments for consulting services from Lundbeck and Medtronic and research support from Lundbeck and Prana Biotechnology. T Driscoll was supported in part by funding from the National Occupational Health and Safety Commission (now Safework Australia). M Ezzati chaired a session and gave a talk at the World Cardiology Congress (WCC), with travel cost reimbursed by the World Heart Federation. At the WCC, he also gave a talk at a session organised by PepsiCo with no financial or other remuneration. F Guillemin did a study on osteoarthritis epidemiology in an institution that received grants from public sources: Assurance-Maladie (CNAMTS) InVS, Inserm, CHU de Nancy, CHU de Nice, Conseil Regional de Lorraine, Societe Francaise de Negma-Lerads, Pfizer, Pierre Fabre Medicaments, Sanofi-Aventis France. H J Hoffman is a US Federal Government employee of the National Institutes of Health (NIH). P J Hotez reports holding several positions: Dean, National School of Tropical Medicine, Baylor College of Medicine; Director, Sabin Vaccine Institute Texas Children's Hospital Center for Vaccine Development; and President, Sabin Vaccine Institute. He also is an inventor on several patents: 5,527,937 "Hookworm Anticoagulant"; 5,753,787 "Nucleic Acids for Ancylostoma Secreted Proteins"; 7,303,752 B2 "Hookworm vaccine"; 12/492,734 "Human Hookworm Vaccine"; 61/077,256 "Multivalent Anthelminthic Vaccine"; and PCT-20100701/0.20.5.18 "Malaria Transmission blocking vaccine". G A Mensah is a former employee of PepsiCo. F Perez-Ruiz was an advisor for Ardea, Menarini, Novartis, Metabolex; was a member of the Speaker's Bureau for Menarini, Novartis; an advisor for educational issues for Savient; led investigation grants for the Spanish Health Ministry, Hospital de Cruces Rheumatology Association; and was principal investigator in clinical trials for Ardea. G V Polanczyk has served as a speaker or consultant to Eli-Lily, Novartis, Janssen-Cilag, and Shire Pharmaceuticals, developed educational material for Janssen-Cilag, and received an independent investigator grant from Novartis and from the National Council for Scientific and Technological Development (CNPq, Brazil). L Rushton received honorarium for board membership of the European Centre for Ecotoxicology and Toxicology of Chemicals and received research grants to Imperial College London (as PI) from the European Chemical Industry Council (CEFIC) and CONCAWE (Conservation of Clean Air and Water Europe). J A Singh has received research grants from Takeda and Savient and consultant fees from Savient, Takeda, Ardea, Regeneron, Allergan, URL pharmaceuticals, and Novartis. J A Singh is a member of the executive of OMERACT, an organisation that develops outcome measures in rheumatology and receives arms-length funding from 36 companies; a member of the American College of Rheumatology's Guidelines Subcommittee of the Quality of Care Committee; and a member of the Veterans Affairs Rheumatology Field Advisory Committee. J A Singh is supported by research grants from the National Institutes of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), National Institute on Aging (NIA), National Cancer Institute (NCI) and the Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs) and is also supported by the resources and the use of facilities at the VA Medical Center at Birmingham, Alabama, USA.; We would like to thank the countless individuals who have contributed to the Global Burden of Disease Study 2010 in various capacities. We would also like to specifically acknowledge the important contribution to this work from multiple staff members of the World Health Organization. We also wish to express our gratitude to the following organizations that hosted consultations during the final stages of the analytic process, providing valuable feedback about the results and the data to improve the study's findings overall: Pan American Health Organization; Eastern Mediterranean Regional Office of WHO; UNAIDS; Ministry of Health, Brazil; China Centers for Disease Control; and the University of Zambia. We would like to thank Lori M Newman, Jordis Ott, Poul Erik Petersen, Shekhar Saxena, and Gretchen A Stevens for their collaboration and input into the analyses and estimates. Finally, we would like to acknowledge the extensive support from all staff members at the Institute for Health Metrics and Evaluation and specifically thank: James Bullard, Andrew Ernst, and Serkan Yalcin for their tireless support of the computational infrastructure required to produce the results; Linda A Ettinger for her expert administrative support in order to facilitate communication and coordination amongst the authors; Peter Speyer, Abigail McLain, Katherine Leach-Kemon, and Eden Stork for their persistent and valuable work to gain access to and catalog as much data as possible to inform the estimates; Erin C Mullany for her systematic efforts in organizing drafts of papers, formatting correspondence with expert groups, and preparing the final manuscript; Brad Bell for his review, critiques, and insights about the DisMod-MR software which helped to improve its performance and results; and Jiaji Du for his work developing the user interface for the DisMod-MR software so that multiple expert groups could use it and easily assess the results. The following individuals would like to acknowledge various forms of institutional support. J P Abraham, B Bartels, and P Yeh recognize the support of the World Bank Global Road Safety Facility and Department of Global Health & Population, Harvard School of Public Health, and the World Health Organization Violence and Injury Prevention. B Bikbov acknowledges support from the Moscow State University of Medicine and Dentistry, Moscow, Russia; Academician V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs, Moscow, Russia; International Society of Nephrology. R Bourne acknowledges the Vision & Eye Research Unit, Postgraduate Medical Institute, Anglia Ruskin University, Cambridge, UK. S Brooker is supported by a Wellcome Trust Senior Fellowship in Basic Biomedical Science (098045). T S Brugha received funding from the Department of Health London, for the National Health Service Information Centre, by the University of Leicester. R Buchbinder is partially funded by an Australian National Health and Medical Research Council (NHMRC) Practitioner Fellowship, Monash University and Cabrini Health. P Burney and D Jarvis acknowledge that the Chronic Respiratory Disease Group received support from the BUPA Foundation, who had no role in study design, data collection and analysis, interpretation of data, decision to publish, or preparation of the manuscript. C Cella, M Cortinovis, F Gaspari, V Miglioli, and N Perico on behalf of the entire Genitourinary Expert Group acknowledge the International Society of Nephrology (ISN).; H Chen acknowledges that his participation in this study was in part supported by the intramural research program of the NIH, the National Institute of Environmental Health Sciences. L E Coffeng and W A Stolk received financial support from the Africa Programme for Onchocerciasis Control (WHO/APOC) for their work on onchocerciasis. B C Cowie received institutional support from the Victorian Infectious Diseases Reference Laboratory, Melbourne, Australia. M Cross and L March acknowledge the University of Sydney (USYD); Institute of Bone and Joint Research, University of Sydney, Department of Rheumatology, Royal North Shore Hospital, St Leonards NSW 2065 Australia. N Dahodwala was supported by NIH grant K23 AG034236 and the Parkinson Council while working on this project. L Degenhardt is supported by an Australian NHMRC Senior Research Fellowship and funding to support her work for illicit drug dependence was provided by the Australian National Drug and Alcohol Research Centre of the University of New South Wales, Australia. R Dellavalle was supported by the US Department of Veterans Affairs while contributing to this study. S Derrett acknowledges the Health Research Council of New Zealand and the University of Otago for their support. V Feigin and R Krishnamurthi were supported by the National Institute for Stroke and Applied Neurosciences, AUT University. E Fevre acknowledges the Wellcome Trust for grant 085308. W Hall was supported by an NHMRC Australia Fellowship. R Havmoeller was supported by a grant from the Swedish Research Council (#2011-1071). D Hoy was supported by the Bill and Melinda Gates Foundation and the Australian National Health and Medical Research Council. K H Jacobsen was supported by the World Health Organization for her work on hepatitis A. N Kawakami notes that the collection of data ultimately used in this study was supported by the following grants: The World Mental Health Japan (WMH-J) is supported by the Grant for Research on Psychiatric and Neurological Diseases and Mental Health (H13-SHOGAI-023, H14-TOKUBETSU-026, H16-KOKORO-013) from the Japan Ministry of Health, Labour, and Welfare. He would like to thank staff members, field coordinators, and interviewers of the WMH Japan 2002-2004 Survey. L L Laslett is supported by an Australian Government Australian Postgraduate Award. She also notes that the TasOAC study, the results of which were used in this research, was supported by the National Health and Medical Research Council of Australia; Arthritis Foundation of Australia; Tasmanian Community Fund; Masonic Centenary Medical Research Foundation, Royal Hobart Hospital Research Foundation, and University of Tasmania Institutional Research Grants Scheme. R Malekzadeh funding from research grant of Tehran University of Medical Sciences to do the related studies. R Matzopoulos acknowledges the two institutions that support his research work: South African Medical Research Council Burden of Disease Research Unit; and the University of Cape Town School of Public Health and Family Medicine. T Merriman acknowledges the Health Research Council of New Zealand. K Naidoo was supported by the Brien Holden Vision Institute. P Nelson was supported by the National Drug and Alcohol Research Centre (UNSW, Australia). R G Nelson acknowledges his research was supported in part by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. C Olives was funded in part by the Biostatistics, Epidemiologic and Bioinformatic Training in Environmental Health Training Grant (ES015459).; D Ozgediz acknowledges the staff and collaborators at the Mulago Hospital and Makerere University in Kampala, Uganda. K Pesudovs received institutional support from Flinders University. R Room's position at the University of Melbourne and Turning Point Alcohol and Drug Centre is funded by the Foundation for Alcohol Research and Education and the Victorian Department of Health. J A Salomon received support from the Burke Global Health Fellowship while working on this study. U Sampson received funding support from the Harold Amos Medical Faculty Development Award of the Robert Wood Johnson Foundation and the Vanderbilt Clinical and Translational Scholars Award. L Sanchez-Riera acknowledges the Spanish Society of Rheumatology (Sociedad Espanola de Reumatologia). M Segui-Gomez's participation was partly supported by funds from the European Center for Injury Prevention, Universidad de Navarra. E Smith acknowledges the Department of Health and Ageing, Commonwealth Government of Australia, Institute of Bone and Joint Research (IBJR), University of Sydney (USYD). G D Thurston was supported in part by Center grant ES00260 from the National Institute of Environmental Health Sciences. D J Weatherall was supported by the Wellcome Trust UK, the Medical Research Council UK and the Anthony Cerami and Ann Dunne Research Trust. NR 109 TC 1603 Z9 1678 U1 117 U2 585 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 DEC 15 PY 2012 VL 380 IS 9859 BP 2163 EP 2196 PG 34 WC Medicine, General & Internal SC General & Internal Medicine GA 055AL UT WOS:000312387000015 PM 23245607 ER PT J AU Murray, CJL Vos, T Lozano, R Naghavi, M Flaxman, AD Michaud, C Ezzati, M Shibuya, K Salomon, JA Abdalla, S Aboyans, V Abraham, J Ackerman, I Aggarwal, R Ahn, SY Ali, MK Alvarado, M Anderson, HR Anderson, LM Andrews, KG Atkinson, C Baddour, LM Bahalim, AN Barker-Collo, S Barrero, LH Bartels, DH Basanez, MG Baxter, A Bell, ML Benjamin, EJ Bennett, D Bernabe, E Bhalla, K Bhandari, B Bikbov, B Bin Abdulhak, A Birbeck, G Black, JA Blencowe, H Blore, JD Blyth, F Bolliger, I Bonaventure, A Boufous, SA Bourne, R Boussinesq, M Braithwaite, T Brayne, C Bridgett, L Brooker, S Brooks, P Brugha, TS Bryan-Hancock, C Bucello, C Buchbinder, R Buckle, G Budke, CM Burch, M Burney, P Burstein, R Calabria, B Campbell, B Canter, CE Carabin, H Carapetis, J Carmona, L Cella, C Charlson, F Chen, HL Cheng, ATA Chou, D Chugh, SS Coffeng, LE Colan, SD Colquhoun, S Colson, KE Condon, J Connor, MD Cooper, LT Corriere, M Cortinovis, M De Vaccaro, KC Couser, W Cowie, BC Criqui, MH Cross, M Dabhadkar, KC Dahiya, M Dahodwala, N Damsere-Derry, J Danaei, G Davis, A De Leo, D Degenhardt, L Dellavalle, R Delossantos, A Denenberg, J Derrett, S Des Jarlais, DC Dharmaratne, SD Dherani, M Diaz-Torne, C Dolk, H Dorsey, ER Driscoll, T Duber, H Ebel, B Edmond, K Elbaz, A Ali, SE Erskine, H Erwin, PJ Espindola, P Ewoigbokhan, SE Farzadfar, F Feigin, V Felson, DT Ferrari, A Ferri, CP Fevre, EM Finucane, MM Flaxman, S Flood, L Foreman, K Forouzanfar, MH Fowkes, FGR Fransen, M Freeman, MK Gabbe, BJ Gabriel, SE Gakidou, E Ganatra, HA Garcia, B Gaspari, F Gillum, RF Gmel, G Gonzalez-Medina, D Gosselin, R Grainger, R Grant, B Groeger, J Guillemin, F Gunnell, D Gupta, R Haagsma, J Hagan, H Halasa, YA Hall, W Haring, D Haro, JM Harrison, JE Havmoeller, R Hay, RJ Higashi, H Hill, C Hoen, B Hoffman, H Hotez, PJ Hoy, D Huang, JJ Ibeanusi, SE Jacobsen, KH James, SL Jarvis, D Jasrasaria, R Jayaraman, S Johns, N Jonas, JB Karthikeyan, G Kassebaum, N Kawakami, N Keren, A Khoo, JP King, CH Knowlton, LM Kobusingye, O Koranteng, A Krishnamurthi, R Laden, F Lalloo, R Laslett, LL Lathlean, T Leasher, JL Lee, YY Leigh, J Levinson, D Lim, SS Limb, E Lin, JK Lipnick, M Lipshultz, SE Liu, W Loane, M Ohno, SL Lyons, R Mabweijano, J MacIntyre, MF Malekzadeh, R Mallinger, L Manivannan, S Marcenes, W March, L Margolis, DJ Marks, GB Marks, R Matsumori, A Matzopoulos, R Mayosi, BM McAnulty, JH McDermott, MM McGill, N McGrath, J Medina-Mora, ME Meltzer, M Mensah, GA Merriman, TR Meyer, AC Miglioli, V Miller, M Miller, TR Mitchell, PB Mock, C Mocumbi, AO Moffitt, TE Mokdad, AA Monasta, L Montico, M Moradi-Lakeh, M Moran, A Morawska, L Mori, R Murdoch, ME Mwaniki, MK Naidoo, K Nair, MN Naldi, L Narayan, KMV Nelson, PK Nelson, RG Nevitt, MC Newton, CR Nolte, S Norman, P Norman, R O'Donnell, M O'Hanlon, S Olives, C Omer, SB Ortblad, K Osborne, R Ozgediz, D Page, A Pahari, B Pandian, JD Rivero, AP Patten, SB Pearce, N Padilla, RP Perez-Ruiz, F Perico, N Pesudovs, K Phillips, D Phillips, MR Pierce, K Pion, S Polanczyk, GV Polinder, S Pope, CA Popova, S Porrini, E Pourmalek, F Prince, M Pullan, RL Ramaiah, KD Ranganathan, D Razavi, H Regan, M Rehm, JT Rein, DB Remuzzi, G Richardson, K Rivara, FP Roberts, T Robinson, C De Leon, FR Ronfani, L Room, R Rosenfeld, LC Rushton, L Sacco, RL Saha, S Sampson, U Sanchez-Riera, L Sanman, E Schwebel, DC Scott, JG Segui-Gomez, M Shahraz, S Shepard, DS Shin, H Shivakoti, R Singh, D Singh, GM Singh, JA Singleton, J Sleet, DA Sliwa, K Smith, E Smith, JL Stapelberg, NJC Steer, A Steiner, T Stolk, WA Stovner, LJ Sudfeld, C Syed, S Tamburlini, G Tavakkoli, M Taylor, HR Taylor, JA Taylor, WJ Thomas, B Thomson, WM Thurston, GD Tleyjeh, IM Tonelli, M Towbin, JRA Truelsen, T Tsilimbaris, MK Ubeda, C Undurraga, EA van der Werf, MJ van Os, J Vavilala, MS Venketasubramanian, N Wang, MR Wang, WZ Watt, K Weatherall, DJ Weinstock, MA Weintraub, R Weisskopf, MG Weissman, MM White, RA Whiteford, H Wiebe, N Wiersma, ST Wilkinson, JD Williams, HC Williams, SRM Witt, E Wolfe, F Woolf, AD Wulf, S Yeh, PH Zaidi, AKM Zheng, ZJ Zonies, D Lopez, AD AF Murray, Christopher J. L. Vos, Theo Lozano, Rafael Naghavi, Mohsen Flaxman, Abraham D. Michaud, Catherine Ezzati, Majid Shibuya, Kenji Salomon, Joshua A. Abdalla, Safa Aboyans, Victor Abraham, Jerry Ackerman, Ilana Aggarwal, Rakesh Ahn, Stephanie Y. Ali, Mohammed K. Alvarado, Miriam Anderson, H. Ross Anderson, Laurie M. Andrews, Kathryn G. Atkinson, Charles Baddour, Larry M. Bahalim, Adil N. Barker-Collo, Suzanne Barrero, Lope H. Bartels, David H. Basanez, Maria-Gloria Baxter, Amanda Bell, Michelle L. Benjamin, Emelia J. Bennett, Derrick Bernabe, Eduardo Bhalla, Kavi Bhandari, Bishal Bikbov, Boris Bin Abdulhak, Aref Birbeck, Gretchen Black, James A. Blencowe, Hannah Blore, Jed D. Blyth, Fiona Bolliger, Ian Bonaventure, Audrey Boufous, Soufi Ane Bourne, Rupert Boussinesq, Michel Braithwaite, Tasanee Brayne, Carol Bridgett, Lisa Brooker, Simon Brooks, Peter Brugha, Traolach S. Bryan-Hancock, Claire Bucello, Chiara Buchbinder, Rachelle Buckle, Geoffrey Budke, Christine M. Burch, Michael Burney, Peter Burstein, Roy Calabria, Bianca Campbell, Benjamin Canter, Charles E. Carabin, Helene Carapetis, Jonathan Carmona, Loreto Cella, Claudia Charlson, Fiona Chen, Honglei Cheng, Andrew Tai-Ann Chou, David Chugh, Sumeet S. Coffeng, Luc E. Colan, Steven D. Colquhoun, Samantha Colson, K. Ellicott Condon, John Connor, Myles D. Cooper, Leslie T. Corriere, Matthew Cortinovis, Monica De Vaccaro, Karen Courville Couser, William Cowie, Benjamin C. Criqui, Michael H. Cross, Marita Dabhadkar, Kaustubh C. Dahiya, Manu Dahodwala, Nabila Damsere-Derry, James Danaei, Goodarz Davis, Adrian De Leo, Diego Degenhardt, Louisa Dellavalle, Robert Delossantos, Allyne Denenberg, Julie Derrett, Sarah Des Jarlais, Don C. Dharmaratne, Samath D. Dherani, Mukesh Diaz-Torne, Cesar Dolk, Helen Dorsey, E. Ray Driscoll, Tim Duber, Herbert Ebel, Beth Edmond, Karen Elbaz, Alexis Ali, Suad Eltahir Erskine, Holly Erwin, Patricia J. Espindola, Patricia Ewoigbokhan, Stalin E. Farzadfar, Farshad Feigin, Valery Felson, David T. Ferrari, Alize Ferri, Cleusa P. Fevre, Eric M. Finucane, Mariel M. Flaxman, Seth Flood, Louise Foreman, Kyle Forouzanfar, Mohammad H. Fowkes, Francis Gerry R. Fransen, Marlene Freeman, Michael K. Gabbe, Belinda J. Gabriel, Sherine E. Gakidou, Emmanuela Ganatra, Hammad A. Garcia, Bianca Gaspari, Flavio Gillum, Richard F. Gmel, Gerhard Gonzalez-Medina, Diego Gosselin, Richard Grainger, Rebecca Grant, Bridget Groeger, Justina Guillemin, Francis Gunnell, David Gupta, Ramyani Haagsma, Juanita Hagan, Holly Halasa, Yara A. Hall, Wayne Haring, Diana Maria Haro, Josep Harrison, James E. Havmoeller, Rasmus Hay, Roderick J. Higashi, Hideki Hill, Catherine Hoen, Bruno Hoffman, Howard Hotez, Peter J. Hoy, Damian Huang, John J. Ibeanusi, Sydney E. Jacobsen, Kathryn H. James, Spencer L. Jarvis, Deborah Jasrasaria, Rashmi Jayaraman, Sudha Johns, Nicole Jonas, Jost B. Karthikeyan, Ganesan Kassebaum, Nicholas Kawakami, Norito Keren, Andre Khoo, Jon-Paul King, Charles H. Knowlton, Lisa Marie Kobusingye, Olive Koranteng, Adofo Krishnamurthi, Rita Laden, Francine Lalloo, Ratilal Laslett, Laura L. Lathlean, Tim Leasher, Janet L. Lee, Yong Yi Leigh, James Levinson, Daphna Lim, Stephen S. Limb, Elizabeth Lin, John Kent Lipnick, Michael Lipshultz, Steven E. Liu, Wei Loane, Maria Ohno, Summer Lockett Lyons, Ronan Mabweijano, Jacqueline MacIntyre, Michael F. Malekzadeh, Reza Mallinger, Leslie Manivannan, Sivabalan Marcenes, Wagner March, Lyn Margolis, David J. Marks, Guy B. Marks, Robin Matsumori, Akira Matzopoulos, Richard Mayosi, Bongani M. McAnulty, John H. McDermott, Mary M. McGill, Neil McGrath, John Elena Medina-Mora, Maria Meltzer, Michele Mensah, George A. Merriman, Tony R. Meyer, Ana-Claire Miglioli, Valeria Miller, Matthew Miller, Ted R. Mitchell, Philip B. Mock, Charles Mocumbi, Ana Olga Moffitt, Terrie E. Mokdad, Ali A. Monasta, Lorenzo Montico, Marcella Moradi-Lakeh, Maziar Moran, Andrew Morawska, Lidia Mori, Rintaro Murdoch, Michele E. Mwaniki, Michael K. Naidoo, Kovin Nair, M. Nathan Naldi, Luigi Narayan, K. M. Venkat Nelson, Paul K. Nelson, Robert G. Nevitt, Michael C. Newton, Charles R. Nolte, Sandra Norman, Paul Norman, Rosana O'Donnell, Martin O'Hanlon, Simon Olives, Casey Omer, Saad B. Ortblad, Katrina Osborne, Richard Ozgediz, Doruk Page, Andrew Pahari, Bishnu Pandian, Jeyaraj Durai Panozo Rivero, Andrea Patten, Scott B. Pearce, Neil Perez Padilla, Rogelio Perez-Ruiz, Fernando Perico, Norberto Pesudovs, Konrad Phillips, David Phillips, Michael R. Pierce, Kelsey Pion, Sebastien Polanczyk, Guilherme V. Polinder, Suzanne Pope, C. Arden, III Popova, Svetlana Porrini, Esteban Pourmalek, Farshad Prince, Martin Pullan, Rachel L. Ramaiah, Kapa D. Ranganathan, Dharani Razavi, Homie Regan, Mathilda Rehm, Juergen T. Rein, David B. Remuzzi, Guiseppe Richardson, Kathryn Rivara, Frederick P. Roberts, Thomas Robinson, Carolyn Rodriguez De Leon, Felipe Ronfani, Luca Room, Robin Rosenfeld, Lisa C. Rushton, Lesley Sacco, Ralph L. Saha, Sukanta Sampson, Uchechukwu Sanchez-Riera, Lidia Sanman, Ella Schwebel, David C. Scott, James Graham Segui-Gomez, Maria Shahraz, Saeid Shepard, Donald S. Shin, Hwashin Shivakoti, Rupak Singh, David Singh, Gitanjali M. Singh, Jasvinder A. Singleton, Jessica Sleet, David A. Sliwa, Karen Smith, Emma Smith, Jennifer L. Stapelberg, Nicolas J. C. Steer, Andrew Steiner, Timothy Stolk, Wilma A. Stovner, Lars Jacob Sudfeld, Christopher Syed, Sana Tamburlini, Giorgio Tavakkoli, Mohammad Taylor, Hugh R. Taylor, Jennifer A. Taylor, William J. Thomas, Bernadette Thomson, W. Murray Thurston, George D. Tleyjeh, Imad M. Tonelli, Marcello Towbin, Jeff Rey A. Truelsen, Thomas Tsilimbaris, Miltiadis K. Ubeda, Clotilde Undurraga, Eduardo A. van der Werf, Marieke J. van Os, Jim Vavilala, Monica S. Venketasubramanian, N. Wang, Mengru Wang, Wenzhi Watt, Kerrianne Weatherall, David J. Weinstock, Martin A. Weintraub, Robert Weisskopf, Marc G. Weissman, Myrna M. White, Richard A. Whiteford, Harvey Wiebe, Natasha Wiersma, Steven T. Wilkinson, James D. Williams, Hywel C. Williams, Sean R. M. Witt, Emma Wolfe, Frederick Woolf, Anthony D. Wulf, Sarah Yeh, Pon-Hsiu Zaidi, Anita K. M. Zheng, Zhi-Jie Zonies, David Lopez, Alan D. TI Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010 SO LANCET LA English DT Article ID PUBLIC-HEALTH UTILITY; RISK-FACTORS; ECONOMIC COST; MORTALITY; POPULATION; AUSTRALIA; COUNTRIES; DEATH; LOST; METAANALYSIS AB Background Measuring disease and injury burden in populations requires a composite metric that captures both premature mortality and the prevalence and severity of ill-health. The 1990 Global Burden of Disease study proposed disability-adjusted life years (DALYs) to measure disease burden. No comprehensive update of disease burden worldwide incorporating a systematic reassessment of disease and injury-specific epidemiology has been done since the 1990 study. We aimed to calculate disease burden worldwide and for 21 regions for 1990, 2005, and 2010 with methods to enable meaningful comparisons over time. Methods We calculated DALYs as the sum of years of life lost (YLLs) and years lived with disability (YLDs). DALYs were calculated for 291 causes, 20 age groups, both sexes, and for 187 countries, and aggregated to regional and global estimates of disease burden for three points in time with strictly comparable definitions and methods. YLLs were calculated from age-sex-country-time-specific estimates of mortality by cause, with death by standardised lost life expectancy at each age. YLDs were calculated as prevalence of 1160 disabling sequelae, by age, sex, and cause, and weighted by new disability weights for each health state. Neither YLLs nor YLDs were age-weighted or discounted. Uncertainty around cause-specific DALYs was calculated incorporating uncertainty in levels of all-cause mortality, cause-specific mortality, prevalence, and disability weights. Findings Global DALYs remained stable from 1990 (2.503 billion) to 2010 (2.490 billion). Crude DALYs per 1000 decreased by 23% (472 per 1000 to 361 per 1000). An important shift has occurred in DALY composition with the contribution of deaths and disability among children (younger than 5 years of age) declining from 41% of global DALYs in 1990 to 25% in 2010. YLLs typically account for about half of disease burden in more developed regions (high-income Asia Pacific, western Europe, high-income North America, and Australasia), rising to over 80% of DALYs in sub-Saharan Africa. In 1990, 47% of DALYs worldwide were from communicable, maternal, neonatal, and nutritional disorders, 43% from non-communicable diseases, and 10% from injuries. By 2010, this had shifted to 35%, 54%, and 11%, respectively. Ischaemic heart disease was the leading cause of DALYs worldwide in 2010 (up from fourth rank in 1990, increasing by 29%), followed by lower respiratory infections (top rank in 1990; 44% decline in DALYs), stroke (fifth in 1990; 19% increase), diarrhoeal diseases (second in 1990; 51% decrease), and HIV/AIDS (33rd in 1990; 351% increase). Major depressive disorder increased from 15th to 11th rank (37% increase) and road injury from 12th to 10th rank (34% increase). Substantial heterogeneity exists in rankings of leading causes of disease burden among regions. Interpretation Global disease burden has continued to shift away from communicable to non-communicable diseases and from premature death to years lived with disability. In sub-Saharan Africa, however, many communicable, maternal, neonatal, and nutritional disorders remain the dominant causes of disease burden. The rising burden from mental and behavioural disorders, musculoskeletal disorders, and diabetes will impose new challenges on health systems. Regional heterogeneity highlights the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account. Because of improved definitions, methods, and data, these results for 1990 and 2010 supersede all previously published Global Burden of Disease results. C1 [Baxter, Amanda; Erskine, Holly; Ferrari, Alize; Khoo, Jon-Paul; Saha, Sukanta; Whiteford, Harvey] Univ Queensland, Queensland Ctr Mental Hlth Res, Brisbane, Qld, Australia. [Vos, Theo; Blore, Jed D.; Charlson, Fiona; Higashi, Hideki; Lee, Yong Yi; Norman, Rosana; Page, Andrew; Lopez, Alan D.] Univ Queensland, Sch Populat Hlth, Brisbane, Qld, Australia. 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[Cooper, Leslie T.] Loyola Univ, Sch Med, Chicago, IL 60611 USA. [Corriere, Matthew] Wake Forest Univ, Sch Publ Hlth Sci, Winston Salem, NC 27109 USA. [De Vaccaro, Karen Courville] Hosp Dr Gustavo N Collado, Puerto Chitre, Panama. [Cowie, Benjamin C.] Victorian Infect Dis Reference Lab, Melbourne, Vic, Australia. [Criqui, Michael H.; Denenberg, Julie] Univ Calif San Diego, San Diego, CA 92103 USA. [Dahodwala, Nabila; Margolis, David J.] Univ Penn, Philadelphia, PA 19104 USA. [Damsere-Derry, James] Bldg & Rd Res Inst, Kumasi, Ghana. [Davis, Adrian] MRC Hearing & Commun Grp, Manchester, Lancs, England. [Lalloo, Ratilal] Griffith Univ, Sch Dent & Oral Hlth, Brisbane, Qld 4111, Australia. [Lalloo, Ratilal] Griffith Univ, Populat & Social Hlth Res Program, Brisbane, Qld 4111, Australia. [Dellavalle, Robert] Denver VA Med Ctr, Denver, VA USA. [Derrett, Sarah; Grainger, Rebecca; Merriman, Tony R.; Taylor, William J.; Thomson, W. Murray] Univ Otago, Dunedin, New Zealand. [Des Jarlais, Don C.] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA. [Dharmaratne, Samath D.] Univ Peradeniya, Peradeniya, Sri Lanka. [Dherani, Mukesh] Univ Liverpool, Liverpool L69 3BX, Merseyside, England. [Diaz-Torne, Cesar] Hosp Santa Creu & Sant Pau, Barcelona, Spain. [Dolk, Helen; Loane, Maria] Univ Ulster, Ulster, Ireland. [Ali, Suad Eltahir] Fed Minist Hlth, Khartoum, Sudan. [Espindola, Patricia] Hosp Maciel, Montevideo, Uruguay. [Ewoigbokhan, Stalin E.] Emerald Publ Hlth Consulting Serv Ltd, Abuja, Nigeria. [Malekzadeh, Reza] Univ Tehran Med Sci, Digest Dis Res Ctr, Tehran, Iran. [Feigin, Valery] Auckland Tech Univ, Natl Inst Stroke & Appl Neurosci, Auckland, New Zealand. [Polanczyk, Guilherme V.] Univ Fed Sao Paulo, Sch Med, Sao Paulo, Brazil. [Flaxman, Seth] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. [Watt, Kerrianne] James Cook Univ, Townsville, Qld 4811, Australia. [Gillum, Richard F.] Howard Univ, Coll Med, Washington, DC USA. [Gmel, Gerhard] Addict Info Switzerland, Lausanne, Switzerland. [Nevitt, Michael C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Groeger, Justina] Suny Downstate Med Ctr, Coll Med, Brooklyn, NY 11203 USA. [Sleet, David A.] Ctr Dis Control & Prevent, Natl Ctr Injury Prevent & Control, Atlanta, GA USA. [Guillemin, Francis] Univ Lorraine, Nancy, France. [Gunnell, David] Univ Bristol, Bristol, Avon, England. [Hagan, Holly; Thurston, George D.] NYU, New York, NY USA. [Halasa, Yara A.; Shahraz, Saeid; Shepard, Donald S.; Undurraga, Eduardo A.] Brandeis Univ, Waltham, MA USA. [Maria Haro, Josep] Univ Barcelona, CIBERSAM, St Boi De Llobregat, Spain. [Havmoeller, Rasmus] Karolinska Univ Hosp, Stockholm, Sweden. [Hill, Catherine] Queen Elizabeth Hosp, Adelaide, SA, Australia. [Hoen, Bruno] Univ Franche Comte, F-25030 Besancon, France. [Hoen, Bruno] Ctr Hosp Reg Univ Besancon, Besancon, France. [Hoffman, Howard] NIDCD, NIH, Bethesda, MD USA. [Nelson, Robert G.] NIDDK, NIH, Bethesda, MD USA. [Hotez, Peter J.] Baylor Coll Med, Natl Sch Trop Med, Waco, TX USA. [Ibeanusi, Sydney E.] Univ Port Harcourt, Port Harcourt, Nigeria. [Jacobsen, Kathryn H.] George Mason Univ, Fairfax, VA 22030 USA. [Jonas, Jost B.] Heidelberg Univ, Med Fac Mannheim, Dept Ophthalmol, Heidelberg, Germany. [Karthikeyan, Ganesan] All India Inst Med Sci, New Delhi, India. [Keren, Andre] Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Cardiol, IL-91010 Jerusalem, Israel. [King, Charles H.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Kobusingye, Olive] Makerere Univ, Sch Publ Hlth, Kampala, Uganda. [Kobusingye, Olive] Univ S Africa, Johannesburg, South Africa. [Koranteng, Adofo] Kwame Nkrumah Univ Sci & Technol, Kumasi, Ghana. [Laslett, Laura L.] Univ Tasmania, Hobart, Tas 7001, Australia. [Leasher, Janet L.] Nova SE Univ, Ft Lauderdale, FL 33314 USA. [Levinson, Daphna] Minist Hlth, Jerusalem, Israel. [Lipshultz, Steven E.; Sacco, Ralph L.; Wilkinson, James D.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Lyons, Ronan] Swansea Univ, Swansea, W Glam, Wales. [Mabweijano, Jacqueline] Mulago Hosp, Kampala, Uganda. [Matsumori, Akira] Asian Pacific Soc Cardiol, Kyoto, Japan. [Matzopoulos, Richard] MRC, Tygerberg, South Africa. [Sliwa, Karen] Univ Cape Town, Hatter Inst, ZA-7925 Cape Town, South Africa. [Mensah, George A.] Univ Cape Town, Dept Med, ZA-7925 Cape Town, South Africa. [McAnulty, John H.] Legacy Hlth Syst, Portland, OR USA. [McDermott, Mary M.] Northwestern Univ, Feinberg Sch Med, Evanston, IL USA. [Elena Medina-Mora, Maria] Natl Inst Psychiat Ramon de la Fuente, Mexico City, DF, Mexico. [Meltzer, Michele] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Miller, Ted R.] Pacific Inst Res & Evaluat, Calverton, MD USA. [Mocumbi, Ana Olga] Natl Inst Hlth, Maputo, Mozambique. [Mocumbi, Ana Olga] Univ Eduardo Mondlane, Maputo, Mozambique. [Moffitt, Terrie E.] Duke Univ, Durham, NC USA. [Monasta, Lorenzo; Montico, Marcella; Ronfani, Luca; Tamburlini, Giorgio] IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy. [Weissman, Myrna M.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Morawska, Lidia] Queensland Univ Technol, Brisbane, Qld 4001, Australia. [Mori, Rintaro] Natl Ctr Child Hlth & Dev, Tokyo, Japan. [Murdoch, Michele E.] Watford Dist Gen Hosp, Watford, England. [Mwaniki, Michael K.] Kemri Wellcome Trust, Kilifi, Kenya. [Naidoo, Kovin] Univ KwaZulu Natal, AVRI, Durban, South Africa. [Naldi, Luigi] Ctr Studi GISED, Bergamo, Italy. [Nolte, Sandra] Charite, D-13353 Berlin, Germany. [O'Donnell, Martin] Natl Univ Ireland Galway, HRB Clin Res Facil, Galway, Ireland. [Osborne, Richard] Deakin Univ, Melbourne, Vic, Australia. [Pahari, Bishnu] BP Koirala Inst Hlth Sci, Dharan, Nepal. [Pandian, Jeyaraj Durai] Betty Cowan Res & Innovat Ctr, Ludhiana, Punjab, India. [Panozo Rivero, Andrea] Hosp Joan 23, La Paz, Bolivia. [Patten, Scott B.] Univ Calgary, Calgary, AB, Canada. [Perez Padilla, Rogelio] Inst Nacl Enfermedades Resp, Mexico City, DF, Mexico. [Perez-Ruiz, Fernando] Hosp Univ Cruces, Baracaldo, Spain. [Phillips, Michael R.] Shanghai Jiao Tong Univ, Shanghai Mental Hlth Ctr, Sch Med, Shanghai 200030, Peoples R China. [Zheng, Zhi-Jie] Shanghai Jiao Tong Univ, Sch Publ Hlth, Shanghai 200030, Peoples R China. [Pope, C. Arden, III] Brigham Young Univ, Provo, UT 84602 USA. [Popova, Svetlana; Rehm, Juergen T.] Ctr Addict & Mental Hlth, Toronto, ON, Canada. [Porrini, Esteban] Hosp Univ Canarias, Tenerif, Spain. [Pourmalek, Farshad] Univ British Columbia, Fac Med, Sch Populat & Publ Hlth, Vancouver, BC, Canada. [Ramaiah, Kapa D.] Vector Control Res Ctr, Pondicherry, India. [Razavi, Homie] Ctr Dis Anal, Louisville, CO USA. [Regan, Mathilda] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Rein, David B.] Univ Chicago, NORC, Chicago, IL 60637 USA. [Rodriguez De Leon, Felipe] Complejo Hosp Caja Seguro Social, Panama City, Panama. [Room, Robin] Turning Point Alcohol & Drug Ctr, Ctr Alcohol Policy Res, Fitzroy, SA, Australia. [Sampson, Uchechukwu] Vanderbilt Univ, Nashville, TN USA. [Schwebel, David C.; Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham, AL USA. [Segui-Gomez, Maria] Minist Interior, Madrid, Spain. [Shin, Hwashin] Hlth Canada, Ottawa, ON K1A 0L2, Canada. [Singh, David] Queens Med Ctr, Honolulu, HI USA. [Stovner, Lars Jacob] Norwegian Univ Sci & Technol, Dept Neurosci, N-7034 Trondheim, Norway. [Syed, Sana; Zaidi, Anita K. M.] Aga Khan Univ, Karachi, Pakistan. [Taylor, Jennifer A.] Drexel Univ, Sch Publ Hlth, Philadelphia, PA 19104 USA. [Tonelli, Marcello] Univ Alberta, Alberta Kidney Dis Network, Edmonton, AB, Canada. [Towbin, Jeff Rey A.] Cincinnati Childrens Hosp, Cincinnati, OH USA. [Truelsen, Thomas] Copenhagen Univ Hosp, Dept Neurol, Herlev, Denmark. [Tsilimbaris, Miltiadis K.] Univ Crete, Sch Med, Iraklion, Greece. [Ubeda, Clotilde] ANLIS, Inst Nacl Epidemiol, Malbran, Argentina. [van der Werf, Marieke J.] KNCV TB Fdn, The Hague, Netherlands. [van Os, Jim] Maastricht Univ, Med Ctr, Maastricht, Netherlands. [Venketasubramanian, N.] Natl Univ Singapore, Singapore 117548, Singapore. [Wang, Wenzhi] Capital Med Univ, Beijing Neurosurg Inst, Beijing, Peoples R China. [Weinstock, Martin A.] Brown Univ, Providence, RI 02912 USA. [Weintraub, Robert] Royal Childrens Hosp, Melbourne, Vic, Australia. [Weintraub, Robert] Murdoch Childrens Res Inst, Melbourne, Vic, Australia. [Williams, Hywel C.] Univ Nottingham, Nottingham NG7 2RD, England. [Williams, Sean R. M.] Hollywood Orthopaed Grp, Perth, WA, Australia. [Wolfe, Frederick] Arthrit Res, Wichita, KS USA. [Woolf, Anthony D.] Royal Cornwall Hosp, Truro, England. [Yeh, Pon-Hsiu] London Sch Econ, London WC2A 2AE, England. [Zonies, David] Landstuhl Reg Med Ctr, Landstuhl, Germany. RP Murray, CJL (reprint author), Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA. EM cjlm@uw.edu RI Research ID, CTBCC /O-3564-2014; Prince, Martin/A-9170-2010; Charlson, Fiona/F-5290-2011; Harrison, James/B-8958-2009; Whiteford, Harvey/A-4840-2009; Ferri, Cleusa/B-2922-2010; Tonelli, Marcello/B-3028-2009; Haro, Josep Maria/D-1423-2011; Carabin, Helene/B-7600-2016; Patten, Scott/B-4434-2011; Monasta, Lorenzo/B-1388-2012; Bolliger, Ian/C-4207-2016; Stovner, Lars/D-5025-2014; Moffitt, Terrie/D-5295-2011; Lopez, Alan/F-1487-2010; Laslett, Laura/G-3973-2011; Nolte, Sandra/B-7498-2008; Narayan, K.M. Venkat /J-9819-2012; Hall, Wayne/A-3283-2008; Ronfani, Luca/B-6668-2013; Bikbov, Boris/I-4594-2013; Lee, Yong Yi/C-1373-2015; Baxter, Amanda/E-5449-2011; Norman, Paul/C-5485-2013; Saha, Sukanta/K-3774-2012; Lathlean, Tim/K-3653-2013; McGrath, John/G-5493-2010; Montico, Marcella/B-5290-2013; Black, James/A-5917-2010; Erskine, Holly/K-5244-2012; NORMAN, ROSANA/F-2774-2010; Buchbinder, Rachelle/G-2952-2011; Carmona, Loreto/A-2748-2014; Polanczyk, Guilherme/C-2345-2012; Jarvis, Deborah/E-6494-2011; Degenhardt, Louisa/D-4515-2012; Undurraga, Eduardo/I-3739-2014; Higashi, Hideki/D-3797-2011; Boussinesq, Michel/J-7256-2016; Jacobsen, Kathryn/B-5857-2008; Naldi, Luigi/K-6343-2016; Lalloo, Ratilal/O-5624-2014; Scott, James/D-5900-2012; Salomon, Joshua/D-3898-2009; Dellavalle, Robert/L-2020-2013; OI Prince, Martin/0000-0003-1379-7146; Charlson, Fiona/0000-0003-2876-5040; Harrison, James/0000-0001-9893-8491; Whiteford, Harvey/0000-0003-4667-6623; Ferri, Cleusa/0000-0002-1815-7685; Haro, Josep Maria/0000-0002-3984-277X; Patten, Scott/0000-0001-9871-4041; Monasta, Lorenzo/0000-0001-7774-548X; Bolliger, Ian/0000-0001-8055-297X; Moffitt, Terrie/0000-0002-8589-6760; Lopez, Alan/0000-0001-5818-6512; Laslett, Laura/0000-0002-4336-0095; Nolte, Sandra/0000-0001-6185-9423; Narayan, K.M. Venkat /0000-0001-8621-5405; Hall, Wayne/0000-0003-1984-0096; Ronfani, Luca/0000-0001-5710-3914; Bikbov, Boris/0000-0002-1925-7506; Lee, Yong Yi/0000-0003-2359-6823; Baxter, Amanda/0000-0001-8198-9022; Norman, Paul/0000-0003-3406-0506; McGrath, John/0000-0002-4792-6068; Montico, Marcella/0000-0003-0377-8232; Black, James/0000-0002-2200-3179; NORMAN, ROSANA/0000-0002-9742-1957; Carmona, Loreto/0000-0002-4401-2551; Polanczyk, Guilherme/0000-0003-2311-3289; Degenhardt, Louisa/0000-0002-8513-2218; Moradi-Lakeh, Maziar/0000-0001-7381-5305; Taylor, Hugh/0000-0002-9437-784X; Merriman, Tony/0000-0003-0844-8726; Chen, Honglei/0000-0003-3446-7779; Perez-Ruiz, Fernando/0000-0002-5268-1894; Osborne, Richard/0000-0002-9081-2699; Bernabe, Eduardo/0000-0002-1858-3713; Benjamin, Emelia/0000-0003-4076-2336; Newton, Charles/0000-0002-6999-5507; Weissman, Myrna/0000-0003-3490-3075; Mitchell, Philip/0000-0002-7954-5235; Pourmalek, Farshad/0000-0002-2134-0771; Miller, Ted/0000-0002-0958-2639; Mayosi, Bongani/0000-0001-6641-8950; Gabbe, Belinda/0000-0001-7096-7688; Cella, Claudia/0000-0002-9210-0775; Loane, Maria/0000-0002-1206-3637; Undurraga, Eduardo/0000-0002-4425-1253; Cowie, Benjamin/0000-0002-7087-5895; O'Donnell, Martin/0000-0002-7347-7761; O'donnell, Colm/0000-0002-8004-450X; Malekzadeh, Reza/0000-0003-1043-3814; Aggarwal, Rakesh/0000-0001-9689-494X; Mensah, George/0000-0002-0387-5326; Higashi, Hideki/0000-0002-5534-0905; Boussinesq, Michel/0000-0001-6312-0681; Jacobsen, Kathryn/0000-0002-4198-6246; Naldi, Luigi/0000-0002-3160-2835; Lalloo, Ratilal/0000-0001-5822-1269; Scott, James/0000-0002-0744-0688; Salomon, Joshua/0000-0003-3929-5515; Dellavalle, Robert/0000-0001-8132-088X; Hotez, Peter/0000-0001-8770-1042; Ebel, Beth/0000-0001-9310-8325; Mock, Charles/0000-0002-0564-568X FU Berlin Heart Honoraria; Lundbeck; Medtronic; Prana Biotechnology; Safework Australia; Assurance-Maladie (CNAMTS) InVS; Inserm; CHU de Nancy; CHU de Nice; Conseil Regional de Lorraine; Societe Francaise de Negma-Lerads; Pfizer; Pierre Fabre Medicaments; Sanofi-Afentis France; Spanish Health Ministry; Hospital de Cruces Rheumatology Association; Novartis; National Council for Scientific and Technological Development (CNPq, Brazil); Takeda; Savient; Ardea; Regeneron; Allergan; URL pharmaceuticals; 36 companies; National Institutes of Arthritis, Musculoskeletal and Skin Diseases (NIAMS); National Institutes of Aging (NIA); National Cancer Institute (NCI); Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs); Wellcome Trust [098045, 085308]; Department of Health London for the National Health Service Information Centre; University of Leicester; Australian National Health and Medical Research Council (NHMRC); Monash University; Cabrini Health; BUPA Foundation; NIH; National Institute of Environmental Health Sciences; Africa Programme for Onchocerciasis Control (WHO/APOC); Victorian Infectious Diseases Reference Laboratory, Melbourne, Australia; NIH [K23 AG034236]; Parkinson Council; Australian NHMRC; US Department of Veterans Affairs; Health Research Council of New Zealand; University of Otago; National Institute for Stroke and Applied Neurosciences; AUT University; NHMRC; Swedish Research Council [2011-1071]; Bill and Melinda Gates Foundation; Australian National Health and Medical Research Council; World Health Organization; World Mental Health Japan (WMH-J); Japan Ministry of Health, Labour, and Welfare [H13-SHOGAI-023, H14-TOKUBETSU-026, H16-KOKORO-013]; Australian Government; National Health and Medical Research Council of Australia; Arthritis Foundation of Australia; Tasmanian Community Fund; Masonic Centenary Medical Research Foundation; Royal Hobart Hospital Research Foundation; University of Tasmania; Tehran University of Medical Sciences; South African Medical Research Council Burden of Disease Research Unit; University of Cape Town School of Public Health and Family Medicine; Brien Holden Vision Institute; National Drug and Alcohol Research Centre (UNSW, Australia); Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases; Biostatistics, Epidemiologic and Bioinformatic Training in Environmental Health Training Grant [ES015459]; Foundation for Alcohol Research and Education; Victorian Department of Health; Burke Global Health Fellowship; Harold Amos Medical Faculty Development Award of the Robert Wood Johnson Foundation; Vanderbilt Clinical and Translational Scholars Award; Spanish Society of Rheumatology (Sociedad Espanola de Reumatologia); European Center for Injury Prevention, Universidad de Navarra; Department of Health and Ageing; Commonwealth Government of Australia; Institute of Bone and Joint Research (IBJR); University of Sydney (USYD); National Institute of Environmental Health Sciences [ES00260]; Wellcome Trust UK; Medical Research Council UK; Anthony Cerami and Ann Dunne Research Trust FX C E Canter has worked as an Optum Health consultant, Blue Cross Blue Shield consultant, and received Berlin Heart Honoraria and travel fees. E R Dorsey has received payments for consulting services from Lundbeck and Medtronic and research support from Lundbeck and Prana Biotechnology. T Driscoll was supported in part by funding from the National Occupational Health and Safety Commission (now Safework Australia). M Ezzati chaired a session and gave a talk at the World Cardiology Congress (WCC), with travel cost reimbursed by the World Heart Federation. At the WCC, he also gave a talk at a session organised by PepsiCo with no financial or other remuneration. F Guillemin conducted a study on osteoarthritis epidemiology in an institution that received grants from public sources: Assurance-Maladie (CNAMTS) InVS, Inserm, CHU de Nancy, CHU de Nice, Conseil Regional de Lorraine, Societe Francaise de Negma-Lerads, Pfizer, Pierre Fabre Medicaments, Sanofi-Afentis France. H J Hoffman is a US Federal Government employee of the National Institutes of Health (NIH). P J Hotez reports holding several positions: Dean, National School of Tropical Medicine, Baylor College of Medicine; Director, Sabin Vaccine Institute Texas Children's Hospital Center for Vaccine Development; and President, Sabin Vaccine Institute. He also is an inventor on several patents: 5,527,937 "Hookworm Anticoagulant"; 5,753,787 "Nucleic Acids for Ancylostoma Secreted Proteins"; 7,303,752 B2 "Hookworm vaccine"; 12/492,734 "Human Hookworm Vaccine"; 61/077,256 "Multivalent Anthelminthic Vaccine"; and PCT-20100701/0.20.5.18 "Malaria Transmission blocking vaccine". G Mensah is a former employee of PepsiCo. F Perez-Ruiz was an advisor for Ardea, Menarini, Novartis, Metabolex; was a member of the Speaker's Bureau for Menarini, Novartis; an advisor for educational issues for Savient; led investigation grants for the Spanish Health Ministry, Hospital de Cruces Rheumatology Association; and was principal investigator in clinical trials for Ardea. G V Polanczyk has served as a speaker and/or consultant to Eli-Lily, Novartis, Janssen-Cilag, and Shire Pharmaceuticals, developed educational material for Janssen-Cilag, and received an independent investigator grant from Novartis and from the National Council for Scientific and Technological Development (CNPq, Brazil). L Rushton received honorarium for board membership of the European Centre for Ecotoxicology and Toxicology of Chemicals and received research grants to Imperial College London (as PI) from the European Chemical Industry Council (CEFIC) and CONCAWE (Conservation of Clean Air and Water Europe). J A Singh has received research grants from Takeda and Savient and consultant fees from Savient, Takeda, Ardea, Regeneron, Allergan, URL pharmaceuticals and Novartis. J A Singh is a member of the executive of OMERACT, an organisation that develops outcome measures in rheumatology and receives arms-length funding from 36 companies; a member of the American College of Rheumatology's Guidelines Subcommittee of the Quality of Care Committee; and a member of the Veterans Affairs Rheumatology Field Advisory Committee. J A Singh is supported by research grants from the National Institutes of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Aging (NIA), National Cancer Institute (NCI), and the Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs) and is also supported by the resources and the use of facilities at the VA Medical Center at Birmingham, AL, USA.; We would like to thank the countless individuals who have contributed to the Global Burden of Disease 2010 study in various capacities. We would like to specifically acknowledge the important contribution to this work from multiple staff members of the World Health Organization. We also wish to express our gratitude to the following organisations that hosted consultations during the final stages of the analytic process, providing valuable feedback about the results and the data to improve the study's findings overall: Pan American Health Organization; Eastern Mediterranean Regional Office of WHO; UNAIDS; Ministry of Health, Brazil; China Centers for Disease Control; and the University of Zambia. We would like to thank Lori M Newman, Jordis Ott, Poul Erik Petersen, Shekhar Saxena, and Gretchen A Stevens for their collaboration and input into the analyses and estimates. Finally, we would like to acknowledge the extensive support from all staff members at the Institute for Health Metrics and Evaluation and specifically thank: James Bullard, Andrew Ernst, and Serkan Yalcin for their tireless support of the computational infrastructure required to produce the results; Linda A Ettinger for her expert administrative support in order to facilitate communication and coordination amongst the authors; Peter Speyer, Abigail McLain, Katherine Leach-Kemon, and Eden Stork for their persistent and valuable work to gain access to and catalog as much data as possible to inform the estimates; and Erin C Mullany for her systematic efforts in organising drafts of papers, formatting correspondence with expert groups, and preparing the final manuscript. The following individuals would like to acknowledge various forms of institutional support. J P Abraham, B Bartels, and P Yeh recognise the support of the World Bank Global Road Safety Facility and Department of Global Health & Population, Harvard School of Public Health, and the World Health Organization Violence and Injury Prevention. B Bikbov acknowledges support from the Moscow State University of Medicine and Dentistry, Moscow, Russia; Academician V I Shumakov Federal Research Center of Transplantology and Artificial Organs, Moscow, Russia; International Society of Nephrology. R Bourne acknowledges the Vision & Eye Research Unit, Postgraduate Medical Institute, Anglia Ruskin University, Cambridge, UK. S Brooker is supported by a Wellcome Trust Senior Fellowship in Basic Biomedical Science (098045). T S Brugha received funding from the Department of Health London, for the National Health Service Information Centre, by the University of Leicester. R Buchbinder is partially funded by an Australian National Health and Medical Research Council (NHMRC) Practitioner Fellowship, Monash University, and Cabrini Health. P Burney and D Jarvis acknowledge the Chronic Respiratory Disease group received funding from the BUPA Foundation. They had no role in study design, data collection and analysis, interpretation of data, decision to publish, or preparation of the manuscript. C Cella, M Cortinovis, F Gaspari, V Miglioli, and N Perico, on behalf of the entire Genitourinary Expert Group, acknowledge the International Society of Nephrology (ISN). H Chen acknowledges that his participation in this study was in part supported by the intramural research program of the NIH, the National Institute of Environmental Health Sciences. L E Coffeng, and W A Stolk received financial support from the Africa Programme for Onchocerciasis Control (WHO/APOC) for their work on onchocerciasis.; B C Cowie received institutional support from the Victorian Infectious Diseases Reference Laboratory, Melbourne, Australia. M Cross and L March acknowledge the University of Sydney (USYD); Institute of Bone and Joint Research, University of Sydney, Department of Rheumatology, Royal North Shore Hospital, St Leonards NSW 2065 Australia. N Dahodwala was supported by NIH grant K23 AG034236 and the Parkinson Council while working on this project. L Degenhardt is supported by an Australian NHMRC Senior Research Fellowship and funding to support her work for illicit drug dependence was provided by the Australian National Drug and Alcohol Research Centre of the University of New South Wales, Australia. R Dellavalle was supported by the US Department of Veterans Affairs while contributing to this study. S Derrett acknowledges the Health Research Council of New Zealand and the University of Otago for their support. V Feigin and R Krishnamurthi were supported by the National Institute for Stroke and Applied Neurosciences, AUT University. E Fevre acknowledges the Wellcome Trust for grant 085308. W Hall was supported by an NHMRC Australia Fellowship. R Havmoeller was supported by a grant from the Swedish Research Council (#2011-1071). D Hoy was supported by the Bill and Melinda Gates Foundation and the Australian National Health and Medical Research Council. K H Jacobsen was supported by the World Health Organization for her work on hepatitis A. N Kawakami notes that the collection of data ultimately used in this study was supported by the following grants: The World Mental Health Japan (WMH-J) is supported by the Grant for Research on Psychiatric and Neurological Diseases and Mental Health (H13-SHOGAI-023, H14-TOKUBETSU-026, H16-KOKORO-013) from the Japan Ministry of Health, Labour, and Welfare. He would like to thank staff members, field coordinators, and interviewers of the WMH Japan 2002-2004 Survey. L L Laslett is supported by an Australian Government Australian Postgraduate Award. She also notes that the TasOAC study, the results of which were used in this research, was supported by the National Health and Medical Research Council of Australia; Arthritis Foundation of Australia; Tasmanian Community Fund; Masonic Centenary Medical Research Foundation, Royal Hobart Hospital Research Foundation, and University of Tasmania Institutional Research Grants Scheme. R Malekzadeh received funding from a research grant of Tehran University of Medical Sciences to do the related studies. R Matzopoulos acknowledges the two institutions that support his research work: South African Medical Research Council Burden of Disease Research Unit; and the University of Cape Town School of Public Health and Family Medicine. T Merriman acknowledges the Health Research Council of New Zealand. K Naidoo was supported by the Brien Holden Vision Institute. P Nelson was supported by the National Drug and Alcohol Research Centre (UNSW, Australia). R G Nelson acknowledges his research was supported in part by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. C Olives was funded in part by the Biostatistics, Epidemiologic and Bioinformatic Training in Environmental Health Training Grant (ES015459). D Ozgediz acknowledges the staff and collaborators at the Mulago Hospital and Makerere University in Kampala, Uganda. K Pesudovs received institutional support from Flinders University.; R Room's position at the University of Melbourne and Turning Point Alcohol and Drug Centre is funded by the Foundation for Alcohol Research and Education and the Victorian Department of Health. J A Salomon received support from the Burke Global Health Fellowship while working on this study. U Sampson received funding support from the Harold Amos Medical Faculty Development Award of the Robert Wood Johnson Foundation and the Vanderbilt Clinical and Translational Scholars Award. L Sanchez-Riera acknowledges the Spanish Society of Rheumatology (Sociedad Espanola de Reumatologia). M Segui-Gomez's participation was partly supported by funds from the European Center for Injury Prevention, Universidad de Navarra. E Smith acknowledges the Department of Health and Ageing, Commonwealth Government of Australia, Institute of Bone and Joint Research (IBJR), University of Sydney (USYD). G D Thurston was supported in part by Center grant ES00260 from the National Institute of Environmental Health Sciences. D J Weatherall was supported by the Wellcome Trust UK, the Medical Research Council UK and the Anthony Cerami and Ann Dunne Research Trust. NR 112 TC 2073 Z9 2153 U1 92 U2 717 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 DEC 15 PY 2012 VL 380 IS 9859 BP 2197 EP 2223 PG 27 WC Medicine, General & Internal SC General & Internal Medicine GA 055AL UT WOS:000312387000016 PM 23245608 ER PT J AU Smith, MJ Walker, JA Shen, YP Stemmer-Rachamimov, A Gusella, JF Plotkin, SR AF Smith, Miriam J. Walker, James A. Shen, Yiping Stemmer-Rachamimov, Anat Gusella, James F. Plotkin, Scott R. TI Expression of SMARCB1 (INI1) mutations in familial schwannomatosis SO HUMAN MOLECULAR GENETICS LA English DT Article ID RHABDOID TUMORS; NF2; GENE; INI1/SMARCB1; HSNF5/INI1 AB Genetic changes in the SMARCB1 tumor suppressor gene have recently been reported in tumors and blood from families with schwannomatosis. Exon scanning of all nine SMARCB1 exons in genomic DNA from our cohort of families meeting the criteria for odefinite' or opresumptive' schwannomatosis previously revealed constitutional alterations in 13 of 19 families (68). Screening of four new familial schwannomatosis probands identified one additional constitutional alteration. We confirmed the presence of mRNA transcripts for two missense alterations, four mutations of conserved splice motifs and two additional mutations, in less conserved sequences, which also affect splicing. Furthermore, we found that transcripts for a rare 3-untranslated region (c.82C T) alteration shared by four unrelated families did not produce splice variants but did show unequal allelic expression, suggesting that the alteration is either causative itself or linked to an unidentified causative mutation. Overexpression studies in cells lacking SMARCB1 suggest that mutant SMARCB1 proteins, like wild-type SMARCB1 protein, retain the ability to suppress cyclin D1 activity. These data, together with the expression of SMARCB1 protein in a proportion of cells from schwannomatosis-related schwannomas, suggest that these tumors develop through a mechanism that is distinct from that of rhabdoid tumors in which SMARCB1 protein is completely absent in tumor cells. C1 [Smith, Miriam J.; Walker, James A.; Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Walker, James A.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Walker, James A.; Shen, Yiping; Gusella, James F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Div Neuropathol, Boston, MA 02114 USA. [Plotkin, Scott R.] Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Boston, MA 02114 USA. RP Plotkin, SR (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM splotkin@partners.org FU NINDS [NS24279]; Harvard Medical School Center for Neurofibromatosis and Allied Disorders; DOD [W81XWH-09-1-0487]; Children's Tumor Foundation; Association for International Cancer Research FX This work was supported in part by NINDS grant NS24279 and by the Harvard Medical School Center for Neurofibromatosis and Allied Disorders. J.A.W. is supported by the DOD (W81XWH-09-1-0487). M.J.S. is currently supported by the Children's Tumor Foundation and the Association for International Cancer Research. NR 17 TC 21 Z9 23 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC 15 PY 2012 VL 21 IS 24 BP 5239 EP 5245 DI 10.1093/hmg/dds370 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 049ES UT WOS:000311965600001 PM 22949514 ER PT J AU Siddiq, A Couch, FJ Chen, GK Lindstrom, S Eccles, D Millikan, RC Michailidou, K Stram, DO Beckmann, L Rhie, SK Ambrosone, CB Aittomaki, K Amiano, P Apicella, C Baglietto, L Bandera, EV Beckmann, MW Berg, CD Bernstein, L Blomqvist, C Brauch, H Brinton, L Bui, QM Buring, JE Buys, SS Campa, D Carpenter, JE Chasman, DI Chang-Claude, J Chen, C Clavel-Chapelon, F Cox, A Cross, SS Czene, K Deming, SL Diasio, RB Diver, WR Dunning, AM Durcan, L Ekici, AB Fasching, PA Feigelson, HS Fejerman, L Figueroa, JD Fletcher, O Flesch-Janys, D Gaudet, MM Gerty, SM Rodriguez-Gil, JL Giles, GG van Gils, CH Godwin, AK Graham, N Greco, D Hall, P Hankinson, SE Hartmann, A Hein, R Heinz, J Hoover, RN Hopper, JL Hu, JJ Huntsman, S Ingles, SA Irwanto, A Isaacs, C Jacobs, KB John, EM Justenhoven, C Kaaks, R Kolonel, LN Coetzee, GA Lathrop, M Marchand, L Lee, AM Lee, IM Lesnick, T Lichtner, P Liu, JJ Lund, E Makalic, E Martin, NG McLean, CA Meijers-Heijboer, H Meindl, A Miron, P Monroe, KR Montgomery, GW Muller-Myhsok, B Nickels, S Nyante, SJ Olswold, C Overvad, K Palli, D Park, DJ Palmer, JR Pathak, H Peto, J Pharoah, P Rahman, N Rivadeneira, F Schmidt, DF Schmutzler, RK Slager, S Southey, MC Stevens, KN Sinn, HP Press, MF Ross, E Riboli, E Ridker, PM Schumacher, FR Severi, G Silva, ID Stone, J Sund, M Tapper, WJ Thun, MJ Travis, RC Turnbull, C Uitterlinden, AG Waisfisz, Q Wang, XS Wang, ZM Weaver, J Schulz-Wendtland, R Wilkens, LR Van Den Berg, D Zheng, W Ziegler, RG Ziv, E Nevanlinna, H Easton, DF Hunter, DJ Henderson, BE Chanock, SJ Garcia-Closas, M Kraft, P Haiman, CA Vachon, CM AF Siddiq, Afshan Couch, Fergus J. Chen, Gary K. Lindstrom, Sara Eccles, Diana Millikan, Robert C. Michailidou, Kyriaki Stram, Daniel O. Beckmann, Lars Rhie, Suhn Kyong Ambrosone, Christine B. Aittomaki, Kristiina Amiano, Pilar Apicella, Carmel Baglietto, Laura Bandera, Elisa V. Beckmann, Matthias W. Berg, Christine D. Bernstein, Leslie Blomqvist, Carl Brauch, Hiltrud Brinton, Louise Bui, Quang M. Buring, Julie E. Buys, Saundra S. Campa, Daniele Carpenter, Jane E. Chasman, Daniel I. Chang-Claude, Jenny Chen, Constance Clavel-Chapelon, Francoise Cox, Angela Cross, Simon S. Czene, Kamila Deming, Sandra L. Diasio, Robert B. Diver, W. Ryan Dunning, Alison M. Durcan, Lorraine Ekici, Arif B. Fasching, Peter A. Feigelson, Heather Spencer Fejerman, Laura Figueroa, Jonine D. Fletcher, Olivia Flesch-Janys, Dieter Gaudet, Mia M. Gerty, Susan M. Rodriguez-Gil, Jorge L. Giles, Graham G. van Gils, Carla H. Godwin, Andrew K. Graham, Nikki Greco, Dario Hall, Per Hankinson, Susan E. Hartmann, Arndt Hein, Rebecca Heinz, Judith Hoover, Robert N. Hopper, John L. Hu, Jennifer J. Huntsman, Scott Ingles, Sue A. Irwanto, Astrid Isaacs, Claudine Jacobs, Kevin B. John, Esther M. Justenhoven, Christina Kaaks, Rudolf Kolonel, Laurence N. Coetzee, Gerhard A. Lathrop, Mark Le Marchand, Loic Lee, Adam M. Lee, I-Min Lesnick, Timothy Lichtner, Peter Liu, Jianjun Lund, Eiliv Makalic, Enes Martin, Nicholas G. McLean, Catriona A. Meijers-Heijboer, Hanne Meindl, Alfons Miron, Penelope Monroe, Kristine R. Montgomery, Grant W. Mueller-Myhsok, Bertram Nickels, Stefan Nyante, Sarah J. Olswold, Curtis Overvad, Kim Palli, Domenico Park, Daniel J. Palmer, Julie R. Pathak, Harsh Peto, Julian Pharoah, Paul Rahman, Nazneen Rivadeneira, Fernando Schmidt, Daniel F. Schmutzler, Rita K. Slager, Susan Southey, Melissa C. Stevens, Kristen N. Sinn, Hans-Peter Press, Michael F. Ross, Eric Riboli, Elio Ridker, Paul M. Schumacher, Fredrick R. Severi, Gianluca Silva, Isabel dos Santos Stone, Jennifer Sund, Malin Tapper, William J. Thun, Michael J. Travis, Ruth C. Turnbull, Clare Uitterlinden, Andre G. Waisfisz, Quinten Wang, Xianshu Wang, Zhaoming Weaver, JoEllen Schulz-Wendtland, Ruediger Wilkens, Lynne R. Van Den Berg, David Zheng, Wei Ziegler, Regina G. Ziv, Elad Nevanlinna, Heli Easton, Douglas F. Hunter, David J. Henderson, Brian E. Chanock, Stephen J. Garcia-Closas, Montserrat Kraft, Peter Haiman, Christopher A. Vachon, Celine M. CA Australian Breast Canc Tissue Bank Familial Breast Canc Study GENICA Consortium TI A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11 SO HUMAN MOLECULAR GENETICS LA English DT Article ID BRCA1 MUTATION CARRIERS; TUMOR SUBTYPES; RISK; POPULATION; CONSORTIUM; MELANOMA AB Genome-wide association studies (GWAS) of breast cancer defined by hormone receptor status have revealed loci contributing to susceptibility of estrogen receptor (ER)-negative subtypes. To identify additional genetic variants for ER-negative breast cancer, we conducted the largest meta-analysis of ER-negative disease to date, comprising 4754 ER-negative cases and 31 663 controls from three GWAS: NCI Breast and Prostate Cancer Cohort Consortium (BPC3) (2188 ER-negative cases; 25 519 controls of European ancestry), Triple Negative Breast Cancer Consortium (TNBCC) (1562 triple negative cases; 3399 controls of European ancestry) and African American Breast Cancer Consortium (AABC) (1004 ER-negative cases; 2745 controls). We performed in silico replication of 86 SNPs at P 1 10(-5) in an additional 11 209 breast cancer cases (946 with ER-negative disease) and 16 057 controls of Japanese, Latino and European ancestry. We identified two novel loci for breast cancer at 20q11 and 6q14. SNP rs2284378 at 20q11 was associated with ER-negative breast cancer (combined two-stage OR 1.16; P 1.1 10(8)) but showed a weaker association with overall breast cancer (OR 1.08, P 1.3 10(6)) based on 17 869 cases and 43 745 controls and no association with ER-positive disease (OR 1.01, P 0.67) based on 9965 cases and 22 902 controls. Similarly, rs17530068 at 6q14 was associated with breast cancer (OR 1.12; P 1.1 10(9)), and with both ER-positive (OR 1.09; P 1.5 10(5)) and ER-negative (OR 1.16, P 2.5 10(7)) disease. We also confirmed three known loci associated with ER-negative (19p13) and both ER-negative and ER-positive breast cancer (6q25 and 12p11). Our results highlight the value of large-scale collaborative studies to identify novel breast cancer risk loci. C1 [Couch, Fergus J.; Lesnick, Timothy; Olswold, Curtis; Slager, Susan; Stevens, Kristen N.; Vachon, Celine M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Couch, Fergus J.; Wang, Xianshu] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Diasio, Robert B.; Lee, Adam M.] Mayo Clin, Dept Pharmacol, Rochester, MN 55905 USA. [Siddiq, Afshan; Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. [Siddiq, Afshan] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Genom Common Dis, London, England. [Chen, Gary K.; Stram, Daniel O.; Rhie, Suhn Kyong; Ingles, Sue A.; Coetzee, Gerhard A.; Monroe, Kristine R.; Schumacher, Fredrick R.; Van Den Berg, David; Henderson, Brian E.; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA. [Press, Michael F.] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Pathol, Los Angeles, CA 90033 USA. [Coetzee, Gerhard A.] Univ So Calif, Keck Sch Med, Dept Urol, Los Angeles, CA 90089 USA. [Lindstrom, Sara; Chen, Constance; Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Eccles, Diana; Durcan, Lorraine; Gerty, Susan M.; Graham, Nikki; Tapper, William J.] Univ Southampton, Fac Med, Southampton SO9 5NH, Hants, England. [Millikan, Robert C.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Millikan, Robert C.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Michailidou, Kyriaki] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. [Dunning, Alison M.; Pharoah, Paul; Easton, Douglas F.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England. [Beckmann, Lars] IQWiG, Inst Qual & Efficiency Hlth Care, Cologne, Germany. [Ambrosone, Christine B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [Aittomaki, Kristiina] Univ Helsinki, Dept Clin Genet, Helsinki, Finland. [Greco, Dario; Nevanlinna, Heli] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland. [Blomqvist, Carl] Helsinki Univ Cent Hosp, Dept Oncol, Helsinki, Finland. [Amiano, Pilar] Consortium Biomed Res Epidemiol & Publ Hlth CIBER, Madrid, Spain. [Apicella, Carmel; Baglietto, Laura; Bui, Quang M.; Giles, Graham G.; Hopper, John L.; Makalic, Enes; Schmidt, Daniel F.; Severi, Gianluca; Stone, Jennifer] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne Sch Populat Hlth, Melbourne, Vic 3010, Australia. [Park, Daniel J.; Southey, Melissa C.] Univ Melbourne, Genet Epidemiol Lab, Dept Pathol, Melbourne, Vic 3010, Australia. [Baglietto, Laura; Giles, Graham G.; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Australian Breast Canc Tissue Bank] Univ Sydney, ABCTB, Sydney, NSW 2006, Australia. [Carpenter, Jane E.] Univ Sydney, Westmead Millennium Inst, Australian Breast Canc Tissue Bank, Sydney, NSW 2006, Australia. [Bandera, Elisa V.] Canc Inst New Jersey, New Brunswick, NJ USA. [Beckmann, Matthias W.; Fasching, Peter A.] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Univ Breast Ctr Franconia, Dept Gynecol & Obstet, Erlangen, Germany. [Hartmann, Arndt] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Inst Pathol, Erlangen, Germany. [Schulz-Wendtland, Ruediger] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Inst Diagnost Radiol, Erlangen, Germany. [Berg, Christine D.] NCI, Early Detect Res Grp, Canc Prevent Div, Rockville, MD USA. [Brinton, Louise; Figueroa, Jonine D.; Hoover, Robert N.; Jacobs, Kevin B.; Nyante, Sarah J.; Wang, Zhaoming; Ziegler, Regina G.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Bernstein, Leslie] Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, City Of Hope, CA USA. Univ Tubingen, Dr Margarete Fischer Bosch Inst Clin Pharmacol, Gene Environm Interact & Breast Canc Germany GENI, Stuttgart, Germany. [Chasman, Daniel I.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Buring, Julie E.; Chasman, Daniel I.; Hankinson, Susan E.; Lee, I-Min; Ridker, Paul M.] Harvard Univ, Sch Med, Boston, MA USA. [Buys, Saundra S.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Campa, Daniele] German Canc Res Ctr, Genom Epidemiol Grp, D-6900 Heidelberg, Germany. [Chang-Claude, Jenny; Hein, Rebecca; Kaaks, Rudolf; Nickels, Stefan] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany. Deutsch Krebsforschungszentrum DKFZ, Heidelberg, Germany. [Clavel-Chapelon, Francoise] Hop Paul Brousse, INSERM UMR 1018, Team Nutr Hormones & Sante Desfemmes 9, Ctr Rech Epidemiol & Sante Populat, Villejuif, France. [Cox, Angela] Univ Sheffield, Inst Canc Studies, Dept Oncol, Sheffield, S Yorkshire, England. [Cross, Simon S.] Univ Sheffield, Acad Unit Pathol, Dept Neurosci, Fac Med Dent & Hlth, Sheffield, S Yorkshire, England. [Czene, Kamila; Hall, Per] Karolinska Inst, S-17177 Stockholm, Sweden. [Deming, Sandra L.; Zheng, Wei] Vanderbilt Univ Sch Med, Vanderbilt Epidemiol Ctr, Div Epidemiol, Dept Med, Nashville, TN USA. [Deming, Sandra L.; Zheng, Wei] Vanderbilt Univ Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Diver, W. Ryan; Gaudet, Mia M.; Thun, Michael J.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany. [Fasching, Peter A.] Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Div Hematol & Oncol, Los Angeles, CA 90024 USA. [Rahman, Nazneen; Turnbull, Clare; Familial Breast Canc Study] Inst Canc Res, Sect Canc Genet, Sutton, Surrey, England. [Garcia-Closas, Montserrat] Inst Canc Res, Sect Epidemiol & Genet, Sutton, Surrey, England. [Feigelson, Heather Spencer; Huntsman, Scott] Kaiser Permanente, Inst Hlth Res, Denver, CO USA. [Fejerman, Laura; Ziv, Elad] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, Inst Human Genet, San Francisco, CA USA. [Fejerman, Laura; Ziv, Elad] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Fletcher, Olivia] Breakthrough Breast Canc Res Ctr, Inst Canc Res, London, England. [Flesch-Janys, Dieter; Heinz, Judith] UCCH, Dept Canc Epidemiol, Clin Canc Registry, Hamburg, Germany. [Flesch-Janys, Dieter; Heinz, Judith] Univ Med Ctr Hamburg Eppendorf, Dept Med Biometr & Epidemiol, Hamburg, Germany. Evangel Kliniken Bonn gGmbH, Dept Internal Med, Bonn, Germany. Univ Bonn, Fac Med, Inst Pathol, Bonn, Germany. German Social Accid Insurance IPA, Inst Prevent & Occupat Med, Bochum, Germany. Saarland Univ Med Ctr, Inst & Outpatient Clin Occupat Med, Homburg, Germany. [GENICA Consortium] Saarland Univ Fac Med, Homburg, Germany. [Rodriguez-Gil, Jorge L.; Hu, Jennifer J.] Univ Miami Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL USA. [Rodriguez-Gil, Jorge L.; Hu, Jennifer J.] Univ Miami Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL USA. [van Gils, Carla H.] Univ Med Ctr, Julius Ctr, Utrecht, Netherlands. [Godwin, Andrew K.; Pathak, Harsh] Kansas Univ Med Ctr, Dept Pathol & Lab Med, Kansas City, KS USA. [Hein, Rebecca] Univ Cologne, PMV Res Grp, Dept Child & Adolescent Psychiat & Psychotherapy, D-50931 Cologne, Germany. [Schmutzler, Rita K.] Univ Cologne, Div Mol Gynaecooncol, Dept Obstet & Gynaecol, D-50931 Cologne, Germany. [Irwanto, Astrid; Liu, Jianjun] Genome Inst Singapore, Div Human Genet, Singapore, Singapore. [Isaacs, Claudine] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Jacobs, Kevin B.; Wang, Zhaoming] NCI Frederick, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD USA. [Jacobs, Kevin B.] Bioinformed Consulting Serv, Gaithersburg, MD USA. [John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA. [John, Esther M.] Stanford Univ Sch Med, Stanford Canc Inst, Stanford, CA USA. [Kolonel, Laurence N.; Le Marchand, Loic; Wilkens, Lynne R.] Univ Hawaii Canc Ctr, Program Epidemiol, Honolulu, HI USA. [Lathrop, Mark] Ctr Natl Genotypage, Evry, France. [Lathrop, Mark] Fdn Jean Dausset, CEPH, Paris, France. [Lichtner, Peter] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany. [Lund, Eiliv] Univ Tromso, Inst Community Med, Tromso, Norway. [Martin, Nicholas G.; Montgomery, Grant W.] Queensland Inst Med Res, QIMR GWAS Collect, Brisbane, Qld 4006, Australia. [McLean, Catriona A.] Alfred Hosp, Melbourne, Vic, Australia. [Meijers-Heijboer, Hanne; Waisfisz, Quinten] Vrije Univ Amsterdam Med Ctr, Sect Oncogenet, Dept Clin Genet, Amsterdam, Netherlands. [Meindl, Alfons] Tech Univ Munich, Div Gynaecol Tumor Genet, Clin Gynaecol & Obstet, Munich, Germany. [Miron, Penelope] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mueller-Myhsok, Bertram] Max Planck Inst Psychiat, D-8000 Munich, Germany. [Overvad, Kim] Aarhus Univ Hosp, Aalborg Hosp, Ctr Cardiovasc Res, Dept Cardiol, Aalborg, Denmark. [Palli, Domenico] ISPO, Canc Res & Prevent Inst, Mol & Nutr Epidemiol Unit, Florence, Italy. [Palmer, Julie R.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. [Peto, Julian; Silva, Isabel dos Santos] London Sch Hyg & Trop Med, Noncommunicable Dis Epidemiol Dept, London WC1, England. [Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med & Epidemiol, Rotterdam, Netherlands. [Sinn, Hans-Peter] Univ Heidelberg Hosp, Dept Pathol, Heidelberg, Germany. [Ross, Eric] Fox Chase Canc Ctr, Dept Biostat, Philadelphia, PA 19111 USA. [Sund, Malin] Umea Univ, Dept Surg, Umea, Sweden. [Travis, Ruth C.] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England. RP Vachon, CM (reprint author), Mayo Clin, Dept Hlth Sci Res, 200 1st St SW,Charlton 6-239, Rochester, MN 55905 USA. EM christopher.haiman@med.usc.edu; vachon.celine@mayo.edu RI Ziv, Elad/L-5396-2014; Bandera, Elisa/M-4169-2014; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; Montgomery, Grant/B-7148-2008; Campa, Daniele/K-1617-2016; Rahman, Nazneen/D-2802-2013; Muller-Myhsok, Bertram/A-3289-2013; Ekici, Arif/C-3971-2013; Clavel-Chapelon, Francoise/G-6733-2014; Berg , Christine/K-1047-2014; OI Giles, Graham/0000-0003-4946-9099; Martin, Nicholas/0000-0003-4069-8020; Czene, Kamila/0000-0002-3233-5695; Palmer, Julie/0000-0002-6534-335X; Sund, Malin/0000-0002-7516-9543; Cross, Simon/0000-0003-2044-1754; Fejerman, Laura/0000-0003-3179-1151; Dunning, Alison Margaret/0000-0001-6651-7166; Rivadeneira, Fernando/0000-0001-9435-9441; Nevanlinna, Heli/0000-0002-0916-2976; Cox, Angela/0000-0002-5138-1099; PALLI, Domenico/0000-0002-5558-2437; Park, Daniel/0000-0002-6354-0931; Bandera, Elisa/0000-0002-8789-2755; Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Montgomery, Grant/0000-0002-4140-8139; Campa, Daniele/0000-0003-3220-9944; Rahman, Nazneen/0000-0003-4376-0440; Greco, Dario/0000-0001-9195-9003 FU Department of Defense [W81XWH-08-1-0383]; Norris Foundation; MEC (National Institutes of Health) [R01-CA63464, R37-CA54281]; CARE (National Institute for Child Health and Development) [NO1-HD-3-3175]; WCHS (U.S. Army Medical Research and Material Command (USAMRMC) [DAMD-17-01-0-0334]; National Institutes of Health [R01-CA100598, CA 65725, CA87969, CA49449, CA67262, CA50385, 5UO1CA098233, CA109147, CA132839, CA54281, CA63464, CA120120]; Breast Cancer Research Foundation; SFBCS (National Institutes of Health) [R01-CA77305]; SFBCS (United States Army Medical Research Program) [DAMD17-96-6071]; NC-BCFR (National Institutes of Health) [U01-CA69417]; CBCS (National Institutes of Health Specialized Program of Research Excellence in Breast Cancer [P50-CA58223]; Center for Environmental Health and Susceptibility, National Institute of Environmental Health Sciences, National Institutes of Health [P30-ES10126]; PLCO (Intramural Research Program, National Cancer Institute, National Institutes of Health); NBHS (National Institutes of Health) [R01-CA100374]; WFBC (National Institutes of Health) [R01-CA73629]; National Cancer Institute, National Institutes of Health [RFA CA-06-503]; MCBCS (National Institutes of Health) [CA122340]; Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]; Breast Cancer Research Foundation (BCRF); MARIE (Deutsche Krebshilfe e.V.) [70-2892-BR I]; Hamburg Cancer Society; German Cancer Research Center (DKFZ); Federal Ministry of Education and Research (BMBF) Germany [01KH0402]; GENICA (Federal Ministry of Education and Research (BMBF) Germany [01KW9975/5, 01KW9976/8, 01KW9977/0, 01KW0114]; Robert Bosch Foundation Stuttgart, Germany; MCCS (Australian NHMRC) [209057, 251553, 504711]; SBCS [Breast Cancer Campaign) [2004Nov49]; Yorkshire Cancer Research; DFCI (DFCI Breast Cancer SPORE NIH) [P50 CA089393]; POSH (Cancer Research UK); DEMOKRITOS [Hellenic Cooperative Oncology Group] [HR R_BG/04]; Greek General Secretary for Research and Technology (GSRT) Program; European Union; BBCC (Dr Mildred Scheel Stiftung of the Deutsche Krebshilfe e.V.); BBCS (Cancer Research UK); Breakthrough Breast Cancer; NHS; National Cancer Research Network (NCRN); LMBC (European Union) [LSHC-CT-2003-503297]; Stichting tegen Kanker [232-2008]; OBCS (Finnish Cancer Foundation); Sigrid Juselius Foundation; University of Finland; Oulu University Hospital; HEBCS (Helsinki University Central Hospital Research Fund); Academy of Finland [132473]; Finnish Cancer Society; Nordic Cancer Union; FCCC [U01CA69631, 5U01CA113916]; University of Kansas Cancer Center; Kansas Bioscience Authority Eminent Scholar Program; RPCI (RPCI DataBank and BioRepository (DBBR); Cancer Center Support Grant Shared Resource [P30 CA016056-32]; SKKDKFZS (Deutsches Krebsforschungszentrum); BIGGS (National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre; Guy's & St. Thomas' NHS Foundation Trust; King's College London and King's College Hospital NHS Foundation Trust; ABCTB (National Health and Medical Research Council of Australia); Cancer Institute NSW; National Breast Cancer Foundation; ABCS (Dutch Cancer Society [2009-4363]; KARBAC (The Stockholm Cancer Society); US National Institutes of Health, National Cancer Institute [U01-CA98233, U01-CA98710, U01-CA98216, U01-CA98758]; NIH/National Cancer Institute, Division of Cancer Epidemiology and Genetics (PLCO); National Heart, Lung, and Blood Institute [HL043851, HL080467]; National Cancer Institute [CA 047988]; Donald W. Reynolds Foundation; Fondation Leducq; Amgen; Wellcome Trust; Cancer Research UK; CR-UK [C1287/A10118, C1287/A12014]; European Community [223175 (HEALTH-F2-2009-223175)]; European Union [BM0606]; National Health and Medical Research Council of Australia; New South Wales Cancer Council; Victorian Health Promotion Foundation (Australia); Institut National de Cancer; Netherlands Organisation for Scientific Research (NWO) as part of a ZonMw/VIDI [91756341]; Deutsche Krebshilfe [107054]; Dietmar-Hopp Foundation; Helmholtz society; e German Cancer Research Centre (DKFZ); German Cancer Aid [107352]; Deutsche Krebshilfe e.V. [70-2892-BR I]; German Cancer Research Center; Agency for Science, Technology and Research of Singapore (A*STAR); US National Institute of Health (NIH); Susan G. Komen Breast Cancer Foundation; Helsinki University Central Hospital Research Fund; Nordic Center of Excellence in Disease Genetics FX AABC was supported by a Department of Defense Breast Cancer Research Program Era of Hope Scholar Award to C. A. H. (W81XWH-08-1-0383) and the Norris Foundation. Each of the participating AABC studies was supported by the following grants: MEC (National Institutes of Health grants R01-CA63464 and R37-CA54281); CARE (National Institute for Child Health and Development grant NO1-HD-3-3175), WCHS (U.S. Army Medical Research and Material Command (USAMRMC) grant DAMD-17-01-0-0334, the National Institutes of Health grant R01-CA100598 and the Breast Cancer Research Foundation, SFBCS (National Institutes of Health grant R01-CA77305 and United States Army Medical Research Program grant DAMD17-96-6071), NC-BCFR (National Institutes of Health grant U01-CA69417), CBCS (National Institutes of Health Specialized Program of Research Excellence in Breast Cancer, grant number P50-CA58223, and Center for Environmental Health and Susceptibility, National Institute of Environmental Health Sciences, National Institutes of Health, grant number P30-ES10126), PLCO (Intramural Research Program, National Cancer Institute, National Institutes of Health) and NBHS (National Institutes of Health grant R01-CA100374), WFBC (National Institutes of Health grant R01-CA73629). The NC-BCFR is one of six sites participating in The Breast Cancer Family Registry (BCFR) which was supported by the National Cancer Institute, National Institutes of Health under RFA CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry and Principal Investigators. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the BCFR, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government or the BCFR.; The TNBCC studies were supported by the following grants: MCBCS (National Institutes of Health Grants CA122340 and a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201) and the Breast Cancer Research Foundation (BCRF); MARIE (Deutsche Krebshilfe e.V., grant number 70-2892-BR I, the Hamburg Cancer Society, the German Cancer Research Center (DKFZ) and the Federal Ministry of Education and Research (BMBF) Germany grant 01KH0402); GENICA (Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0, 01KW0114, and the Robert Bosch Foundation Stuttgart, Germany; MCCS (Australian NHMRC grants 209057, 251553 and 504711 and infrastructure provided by the Cancer Council Victoria); SBCS [Breast Cancer Campaign (grant 2004Nov49 to A. C.), and by Yorkshire Cancer Research core funding]; DFCI (DFCI Breast Cancer SPORE NIH P50 CA089393); POSH (Cancer Research UK); DEMOKRITOS [Hellenic Cooperative Oncology Group research grant (HR R_BG/04) and the Greek General Secretary for Research and Technology (GSRT) Program, Research Excellence II, funded at 75% by the European Union]; BBCC (Dr Mildred Scheel Stiftung of the Deutsche Krebshilfe e.V.); BBCS (Cancer Research UK and Breakthrough Breast Cancer and NHS funding to the NIHR biomedical Research Centre and the National Cancer Research Network (NCRN); LMBC (European Union Framework Programme 6 Project LSHC-CT-2003-503297 (the Cancerdegradome) and by the 'Stichting tegen Kanker' (232-2008); OBCS (Finnish Cancer Foundation, the Sigrid Juselius Foundation, the Academy of Finland, the University of Finland, and Oulu University Hospital); HEBCS (Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society, The Nordic Cancer Union and the Sigrid Juselius Foundation); FCCC (U01CA69631, 5U01CA113916, the University of Kansas Cancer Center and the Kansas Bioscience Authority Eminent Scholar Program); RPCI (RPCI DataBank and BioRepository (DBBR), a Cancer Center Support Grant Shared Resource (P30 CA016056-32)); SKKDKFZS (Deutsches Krebsforschungszentrum); BIGGS (National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust); ABCTB (National Health and Medical Research Council of Australia, The Cancer Institute NSW and the National Breast Cancer Foundation); ABCS (Dutch Cancer Society grant number 2009-4363); KARBAC (The Stockholm Cancer Society).; BPC3 is supported by the US National Institutes of Health, National Cancer Institute under cooperative agreements U01-CA98233 (NHS, NHSII, WHS), U01-CA98710 (CPS2), U01-CA98216 (EPIC), U01-CA98758 (MEC) and Intramural Research Program of NIH/National Cancer Institute, Division of Cancer Epidemiology and Genetics (PLCO). The authors thank Drs Christine Berg and Philip Prorok, Division of Cancer Prevention, NCI, the screening center investigators and staff of the PLCO Cancer Screening Trial, Mr Thomas Riley and staff at Information Management Services, Inc., and Ms Barbara O'Brien and staff at Westat, Inc. for their contributions to the PLCO Cancer Screening Trial.; The WHS is supported by HL043851 and HL080467 from the National Heart, Lung, and Blood Institute and CA 047988 from the National Cancer Institute, the Donald W. Reynolds Foundation and the Fondation Leducq, with collaborative scientific support and funding for genotyping provided by Amgen.; The UK2 GWAS was funded by Wellcome Trust and Cancer Research UK. The WTCCC was funded by the Wellcome Trust. BCAC is funded by CR-UK (C1287/A10118, C1287/A12014) and by the European Community's Seventh Framework Programme under grant agreement no. 223175 (HEALTH-F2-2009-223175) (COGS). Meetings of the BCAC have been funded by the European Union COST programme (BM0606). The ABCFS study was supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the National Cancer Institute, National Institutes of Health under RFA-CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and the Principle Investigators. The University of Melbourne (U01 CA69638) contributed data to this study. The content of this manuscript does not necessarily reflect the views or the policies of the National Cancer Institute or any of the collaborating centers in the BCFR, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government or the BCFR. We extend our thanks to the many women and their families that generously participated in the Australian Breast Cancer Family Study and consented to us accessing their pathology material. J.L.H. is a National Health and Medical Research Council Australia Fellow. M. C. S. is a National Health and Medical Research Council Senior Research Fellow. J.L.H. and M. C. S. are both group leaders of the Victoria Breast Cancer Research Consortium. The BBCS is funded by Cancer Research UK and Breakthrough Breast Cancer and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). The BBCS GWAS received funding from The Institut National de Cancer. The DFBBCS GWAS was funded by The Netherlands Organisation for Scientific Research (NWO) as part of a ZonMw/VIDI grant number 91756341. We thank Muriel Adank for selecting the samples and Margreet Ausems, Christi van Asperen, Senno Verhoef and Rogier van Oldenburg for providing samples from their Clinical Genetic centers. The GC-HBOC was supported by Deutsche Krebshilfe (107054), the Dietmar-Hopp Foundation, the Helmholtz society and the German Cancer Research Centre (DKFZ). The GC-HBOC GWAS was supported by the German Cancer Aid (grant no. 107352). The MARIE study was supported by the Deutsche Krebshilfe e.V. (70-2892-BR I), the Hamburg Cancer Society, the German Cancer Research Center and the genotype work in part by the Federal Ministry of Education and Research (BMBF) Germany (01KH0402). MARIE would like to thank Tracy Slanger and Elke Mutschelknauss for their valuable contributions, and S. Behrens, R. Birr, M. Celik, U. Eilber, B. Kaspereit, N. Knese and K. Smit for their excellent technical assistance. The SASBAC study was supported by funding from the Agency for Science, Technology and Research of Singapore (A*STAR), the US National Institute of Health (NIH) and the Susan G. Komen Breast Cancer Foundation. CGEMS. The Nurses' Health Studies are supported by NIH grants CA 65725, CA87969, CA49449, CA67262, CA50385 and 5UO1CA098233. The HEBCS study has been financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society, The Nordic Cancer Union and the Sigrid Juselius Foundation.; The population allele and genotype frequencies were obtained from the data source funded by the Nordic Center of Excellence in Disease Genetics based on samples regionally selected from Finland, Sweden and Denmark. We thank Drs Kirsimari Aaltonen, Paivi Heikkila and Tuomas Heikkinen and RN Hanna Jantti and Irja Erkkila for their help with the HEBCS data and samples.; The biofeature analysis was supported by NIH grant CA109147.; The breast cancer GWAS in Japanese and Latinos in the MEC (MEC-LAT and MEC-JPT) were supported by NIH grants CA132839, CA54281 and CA63464. Genotyping of the Latino breast cancer cases and controls from SFBCS and NC-BCFR was supported by NIH grant CA120120. NR 28 TC 82 Z9 82 U1 1 U2 41 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC 15 PY 2012 VL 21 IS 24 BP 5373 EP 5384 DI 10.1093/hmg/dds381 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 049ES UT WOS:000311965600012 PM 22976474 ER PT J AU Li, HW Sachs, J Pichardo, C Bronson, R Zhao, GL Sykes, M AF Li, Hao Wei Sachs, Jessica Pichardo, Clarimel Bronson, Roderick Zhao, Guiling Sykes, Megan TI Nonalloreactive T Cells Prevent Donor Lymphocyte Infusion Induced Graft-versus-Host Disease by Controlling Microbial Stimuli SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; KERATINOCYTE GROWTH-FACTOR; REFRACTORY HEMATOLOGIC MALIGNANCIES; ANTIGEN-PRESENTING CELLS; HOMEOSTATIC PROLIFERATION; MURINE CYTOMEGALOVIRUS; IMMUNE RECONSTITUTION; GASTROINTESTINAL-TRACT; CONDITIONING REGIMEN; ALLOGENEIC CHIMERAS AB In mice, graft-versus-host reactions, associated with powerful graft-versus-tumor effects, can be achieved without graft-versus-host disease (GVHD) by delayed administration of donor lymphocyte infusions (DLI) to established mixed chimeras. However, GVHD sometimes occurs after DLI in established mixed chimeric patients. In contrast to mice, in which T cell recovery from the thymus occurs prior to DLI administration, human T cell reconstitution following T cell depleted hematopoietic cell transplantation is slow, resulting in lymphopenia at the time of DLI. We demonstrate in this study that T cell lymphopenia is an independent risk factor for GVHD following DLI in the absence of known inflammatory stimuli. DLI-induced GVHD was prevented in lymphopenic recipients by prior administration of a small number of nonalloreactive polyclonal T cells, insufficient to prevent lymphopenia-associated expansion of subsequently administered T cells, through a regulatory T cell independent mechanism. GVHD was not inhibited by T cells with irrelevant specificity. Moreover, administration of antibiotics reduced the severity of GVHD in lymphopenic hosts. Accumulation of DLI-derived effector T cells and host hematopoietic cell elimination were markedly diminished by regulatory T cell depleted, nonalloreactive T cells. Finally, thymectomized mixed chimeras showed increased GVHD following delayed DLI. Collectively, our data demonstrate that in the absence of known conditioning-induced inflammatory stimuli, T cell lymphopenia is a risk factor for GVHD in mixed chimeras receiving delayed DLI. Our data suggest that the predisposition to GVHD can at least in part be explained by the presence of occult inflammatory stimuli due to the absence of T cells to control microbial infections. The Journal of Immunology, 2012, 189: 5572-5581. C1 [Li, Hao Wei; Zhao, Guiling; Sykes, Megan] Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, New York, NY 10032 USA. [Li, Hao Wei; Sachs, Jessica; Pichardo, Clarimel; Zhao, Guiling; Sykes, Megan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. [Bronson, Roderick] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Sykes, M (reprint author), Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, 650 W 168th St,BB 1502, New York, NY 10032 USA. EM Megan.Sykes@columbia.edu FU National Cancer Institute [P01 CA111519] FX This work was supported by National Cancer Institute Grant P01 CA111519. NR 74 TC 4 Z9 4 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2012 VL 189 IS 12 BP 5572 EP 5581 DI 10.4049/jimmunol.1200045 PG 10 WC Immunology SC Immunology GA 049PM UT WOS:000311995800013 PM 23136200 ER PT J AU Shlipak, MG Scherzer, R Abraham, A Tien, PC Grunfeld, C Peralta, CA Devarajan, P Bennett, M Butch, AW Anastos, K Cohen, MH Nowicki, M Sharma, A Young, MA Sarnak, MJ Parikh, CR AF Shlipak, Michael G. Scherzer, Rebecca Abraham, Alison Tien, Phyllis C. Grunfeld, Carl Peralta, Carmen A. Devarajan, Prasad Bennett, Michael Butch, Anthony W. Anastos, Kathryn Cohen, Mardge H. Nowicki, Marek Sharma, Anjali Young, Mary A. Sarnak, Mark J. Parikh, Chirag R. TI Urinary Markers of Kidney Injury and Kidney Function Decline in HIV-Infected Women SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; KIM-1; NGAL; IL-18; albumin-to-creatinine ratio; cystatin C; kidney injury ID GELATINASE-ASSOCIATED LIPOCALIN; STAGE RENAL-DISEASE; SERUM CYSTATIN-C; ANTIRETROVIRAL THERAPY; CARDIOVASCULAR EVENTS; MOLECULE-1 KIM-1; CARDIAC-SURGERY; INTERAGENCY HIV; ESTIMATING GFR; ALL-CAUSE AB Objective: HIV-infected persons have substantially higher risk of kidney failure than persons without HIV, but serum creatinine levels are insensitive for detecting declining kidney function. We hypothesized that urine markers of kidney injury would be associated with declining kidney function among HIV-infected women. Methods: In the Women's Interagency HIV Study, we measured concentrations of albumin-to-creatinine ratio, interleukin-18 (IL-18), kidney injury marker-1 (KIM-1), and neutrophil gelatinase-associated lipocalin from stored urine among 908 HIV-infected and 289 HIV-uninfected participants. Primary analyses used cystatin C-based estimated glomerular filtration rate (CKD-EPI eGFRcys) as the outcome, measured at baseline and 2 follow-up visits over 8 years; secondary analyses used creatinine (CKD-EPI eGFRcr). Each urine biomarker was categorized into tertiles, and kidney decline was modeled with both continuous and dichotomized outcomes. Results: Compared with the lowest tertiles, the highest tertiles of albumin-to-creatinine ratio (-0.15 mL/min per 1.73 m(2), P < 0.0001), IL-18 (-0.09 mL/min per 1.73 m(2), P < 0.0001) and KIM-1 (-0.06 mL/ min per 1.73 m(2), P < 0.001) were independently associated with faster eGFRcys decline after multivariate adjustment including all 3 biomarkers among HIV-infected women. Among these biomarkers, only IL-18 was associated with each dichotomized eGFRcys outcome: >= 3% (relative risk = 1.40; 95% confidence interval: 1.04 to 1.89); >= 5% (1.88; 1.30 to 2.71); and >= 10% (2.16; 1.20 to 3.88) for the highest versus lowest tertile. In alternative models using eGFRcr, the high tertile of KIM-1 had independent associations with 5% (1.71; 1.25 to 2.33) and 10% (1.78; 1.07 to 2.96) decline, and the high IL-18 tertile with 10% decline (1.97; 1.00 to 3.87). Conclusions: Among HIV-infected women in the Women's Interagency HIV Study cohort, novel urine markers of kidney injury detect risk for subsequent declines in kidney function. C1 [Shlipak, Michael G.; Scherzer, Rebecca; Tien, Phyllis C.; Grunfeld, Carl; Peralta, Carmen A.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94121 USA. [Shlipak, Michael G.; Scherzer, Rebecca; Tien, Phyllis C.; Grunfeld, Carl; Peralta, Carmen A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Abraham, Alison] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Devarajan, Prasad; Bennett, Michael] Cincinnati Childrens Hosp Med Ctr, Div Nephrol & Hypertens, Cincinnati, OH USA. [Butch, Anthony W.] Univ Calif Los Angeles, Dept Pathol & Lab Med, Clin Immunol Res Lab, Los Angeles, CA USA. [Anastos, Kathryn] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Anastos, Kathryn] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Cohen, Mardge H.] Stroger Hosp, Dept Med, Chicago, IL USA. [Cohen, Mardge H.] Rush Univ, Chicago, IL 60612 USA. [Nowicki, Marek] Univ So Calif, Dept Med, Los Angeles, CA USA. [Sharma, Anjali] Suny Downstate Med Ctr, Dept Med, Div Infect Dis, Brooklyn, NY 11203 USA. [Young, Mary A.] Georgetown Univ, Med Ctr, Div Infect Dis, Washington, DC 20007 USA. [Sarnak, Mark J.] Tufts Med Ctr, Div Nephrol, Boston, MA USA. [Parikh, Chirag R.] Yale Univ, Dept Med, Nephrol Sect, New Haven, CT 06520 USA. [Parikh, Chirag R.] Yale Univ, Program Appl Translat Res, New Haven, CT USA. RP Shlipak, MG (reprint author), San Francisco VA Med Ctr, Dept Med, 4150 Clement St,Box 111A1, San Francisco, CA 94121 USA. EM michael.shlipak@ucsf.edu FU Women's Interagency HIV Study (WIHS) Kidney Aging Study [1R01AG034853-01A2]; National Institute of Allergy and Infectious Diseases [UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources (UCSF-CTSI) [UL1 RR024131] FX Supported by the Women's Interagency HIV Study (WIHS) Kidney Aging Study Grant 1R01AG034853-01A2 (principal investigator, M. G. Shlipak), which was administered by the Northern California Institute for Research and Education, and with resources of the Veterans Affairs Medical Center, San Francisco, CA. Data in this manuscript were collected by the WIHS Collaborative Study Group with centers (Principal Investigators) at New York City/Bronx Consortium (K. Anastos); Brooklyn, NY (H. Minkoff); Washington DC Metropolitan Consortium (M. A. Young); The Connie Wofsy Study Consortium of Northern California (R. Greenblatt); Los Angeles County/Southern California Consortium (A. Levine); Chicago Consortium (M. H. Cohen); Data Coordinating Center (S. Gange). The WIHS is funded by the National Institute of Allergy and Infectious Diseases Grants UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590 and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Grant UO1-HD-32632. The study is cofunded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI Grant UL1 RR024131). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. NR 42 TC 21 Z9 21 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD DEC 15 PY 2012 VL 61 IS 5 BP 565 EP 573 DI 10.1097/QAI.0b013e3182737706 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 046UQ UT WOS:000311790300011 PM 23023103 ER PT J AU Donnell-Fink, LA Arbelaez, C Collins, JE Novais, A Case, A Pisculli, ML Reichmann, WM Katz, JN Losina, E Walensky, RP AF Donnell-Fink, Laurel A. Arbelaez, Christian Collins, Jamie E. Novais, Anna Case, Amy Pisculli, Mary L. Reichmann, William M. Katz, Jeffrey N. Losina, Elena Walensky, Rochelle P. TI Acceptability of Fingerstick Versus Oral Fluid Rapid HIV Testing: Results From the Universal Screening for HIV Infection in the Emergency Room (USHER Phase II) Randomized Controlled Trial SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV screening; randomized trial; OraQuick; emergency department ID SEVERITY INDEX; WHOLE-BLOOD; PREFERENCES; EXPERIENCE; SETTINGS; PROGRAM; ROUTINE; CITY AB Background: Oral rapid HIV testing has been reported to have a lower sensitivity and specificity than rapid HIV testing with whole blood and has been associated with clusters of false-positive results. Patient preference for oral rapid HIV testing compared with more invasive whole blood fingerstick may influence the acceptance of rapid HIV testing. Objective: To compare HIV test acceptance rates among patients routinely offered fingerstick compared with those routinely offered oral fluid screening in an urban hospital emergency department. Methods: The Universal Screening for HIV Infection in the Emergency Room Phase II was a single-center, prospective, randomized controlled trial that randomized subjects to either fingerstick or oral rapid HIV screening in an urban academic emergency department. From May 5, 2009, to January 4, 2010, eligible patients aged 18-75 years were invited to participate in the trial. The primary outcome measure was HIV test acceptance rate. Results: 2012 eligible patients were approached, of whom 1651 (82%) consented to trial participation and enrolled. Among those enrolled, 830 and 821 were randomized to the fingerstick and oral fluid arms, respectively. Acceptance of rapid HIV testing was similar in both arms; 67% (553 of 830) of subjects accepted fingerstick testing compared with 69% (565 of 821) who accepted oral (P = 0.34). Conclusions: Although fingerstick rapid HIV testing is more invasive than oral fluid testing, test acceptance rates did not differ. Given the option, preference should therefore be given to fingerstick testing because of its slightly superior test characteristics. System factors such as ease of staff use, necessary Clinical Laboratory Improvement Amendments waivers, laboratory capacity, and HIV prevalence should also be considered. C1 [Donnell-Fink, Laurel A.; Collins, Jamie E.; Reichmann, William M.; Katz, Jeffrey N.; Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Pisculli, Mary L.; Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Dept Med, Boston, MA 02115 USA. [Arbelaez, Christian; Novais, Anna; Case, Amy] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Arbelaez, Christian; Katz, Jeffrey N.; Losina, Elena; Walensky, Rochelle P.] Harvard Univ, Sch Med, Boston, MA USA. [Collins, Jamie E.; Reichmann, William M.; Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Katz, Jeffrey N.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Walensky, Rochelle P.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis & Gen Med, Boston, MA 02114 USA. RP Donnell-Fink, LA (reprint author), Brigham & Womens Hosp, Dept Orthoped Surg, 75 Francis St,BC 4-016, Boston, MA 02115 USA. EM ldonnell-fink@partners.org FU National Institute of Mental Health [R01 MH073445, R01 MH65869]; Doris Duke Charitable Foundation FX This research was funded by the National Institute of Mental Health (R01 MH073445, R01 MH65869) and the Doris Duke Charitable Foundation, Clinical Scientist Development Award to Rochelle P. Walensky. NR 24 TC 5 Z9 5 U1 4 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD DEC 15 PY 2012 VL 61 IS 5 BP 588 EP 592 DI 10.1097/QAI.0b013e31826a6d67 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 046UQ UT WOS:000311790300014 PM 23183149 ER PT J AU Baselga, J Campone, M Cortes, J Iwata, H de Laurentiis, M Jonat, W Di Tomaso, E Hachemi, S Goteti, S Germa, C Massacesi, C Arteaga, C AF Baselga, J. Campone, M. Cortes, J. Iwata, H. de laurentiis, M. Jonat, W. Di Tomaso, E. Hachemi, S. Goteti, S. Germa, C. Massacesi, C. Arteaga, C. TI Phase Ill randomized study of the oral pan-PI3K inhibitor BKM120 with fulvestrant in postmenopausal women with HR+/HER2-locally advanced or metastatic breast cancer resistant to aromatase inhibitor - BELLE-2 SO CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Ctr Rene Gauducheau, F-44035 Nantes, France. Vall dHebron Inst Oncol, Barcelona, Spain. Aichi Canc Ctr Hosp, Nagoya, Aichi 464, Japan. Univ Naples Federico II, Naples, Italy. Univ Kiel, Kiel, Germany. Novartis Inst BioMed Res Inc, Cambridge, MA USA. Novartis Oncol, Paris, France. Novartis Pharmaceut, E Hanover, NJ USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA OT2-3-09 DI 10.1158/0008-5472.5ABCS12-OT2-3-09 PG 2 WC Oncology SC Oncology GA V43TY UT WOS:000209704901090 ER PT J AU Baselga, J Cortes, J Im, SA Clark, E Kiermaier, A Ross, G Swain, SM AF Baselga, J. Cortes, J. Im, S-A Clark, E. Kiermaier, A. Ross, G. Swain, S. M. TI Biomarker analyses in CLEOPATRA: A phase Ill, placebo-controlled study of pertuzumab in HER2-positive, first -line metastatic breast cancer (MBC) SO CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Vall dHebron Univ Hosp, Barcelona, Spain. Seoul Natl Univ, Coll Med, Seoul, South Korea. Roche Prod Ltd, Welwyn Garden City, Herts, England. F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland. MedStar Washington Hosp Ctr, Washington, DC USA. NR 0 TC 12 Z9 12 U1 0 U2 0 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 DEC 15 PY 2012 VL 72 SU 24 MA S5-1 DI 10.1158/0008-5472.SABCS12-S5-1 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704900021 ER PT J AU Bluethmann, SM Allen, JD Hernandez, C Opdyke, KM Gates-Ferris, K Hurlbert, M Harden, E AF Bluethmann, S. M. Allen, J. D. Hernandez, C. Opdyke, K. M. Gates-Ferris, K. Hurlbert, M. Harden, E. TI Women's responses to changes in US Preventive Services Task Force mammography screening guidelines: results from focus groups among ethnically diverse women SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Texas Sch Publ Hlth, Houston, TX USA. Dana Farber Canc Inst, Boston, MA USA. Avon Fdn Breast Canc Crusade, New York, NY USA. Cicatelli & Associates, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P5-14-02 DI 10.1158/0008-5472.SABCS12-P5-14-02 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704901197 ER PT J AU Bradbury, AR Patrick-Miller, L Egleston, B Schwartz, L Tuchman, L Moore, C Rauch, P Sands, C Shorter, R Rowan, B Malhotra, S van Decker, S Schmidheiser, H Sicilia, P Bealin, L Daly, M AF Bradbury, A. R. Patrick-Miller, L. Egleston, B. Schwartz, L. Tuchman, L. Moore, C. Rauch, P. Sands, C. Shorter, R. Rowan, B. Malhotra, S. van Decker, S. Schmidheiser, H. Sicilia, P. Bealin, L. Daly, M. TI Perceptions of breast cancer risk, psychological adjustment and behaviors in adolescent girls at high-risk and population-risk for breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. Univ Chicago, Chicago, IL 60637 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P6-08-01 DI 10.1158/0008-5472.SABCS12-P6-08-01 PG 2 WC Oncology SC Oncology GA V43TY UT WOS:000209704901456 ER PT J AU Breslin, T Hwang, S Mamet, R Hughes, M Otteson, R Edge, S Moy, B Rugo, H Wong, YN Wilson, J Laronga, C Weeks, J Silver, S Marcom, P AF Breslin, T. Hwang, S. Mamet, R. Hughes, M. Otteson, R. Edge, S. Moy, B. Rugo, H. Wong, Y-N Wilson, J. Laronga, C. Weeks, J. Silver, S. Marcom, P. TI Patterns of definitive axillary management in the era prior to reporting ACOSOG Z0011: comparison between NCCN Centers and hospitals in Michigan SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Michigan, Ann Arbor, MI 48109 USA. Duke Univ, Durham, NC 27706 USA. City Hope Natl Med Ctr, Daphne, AL 36526 USA. Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. Roswell Pk Canc Inst, Buffalo, NY USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Fox Chase Canc Ctr, Philadelphia, PA USA. Ohio State Univ, Columbus, OH 43210 USA. H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P1-01-13 PG 2 WC Oncology SC Oncology GA V43TY UT WOS:000209704902099 ER PT J AU Carp, SA Wanyo, CM Specht, M Schapira, L Moy, B Finkelstein, DM Boas, DA Isakoff, SJ AF Carp, S. A. Wanyo, C. M. Specht, M. Schapira, L. Moy, B. Finkelstein, D. M. Boas, D. A. Isakoff, S. J. TI Dynamic tomographic optical breast imaging (TOBI) to monitor response to neoadjuvant therapy in breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P3-06-27 DI 10.1158/0008-5472.SABCS12-P3-06-27 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704900435 ER PT J AU De Nicolo, A Pathania, S Parisini, E Joukov, V AF De Nicolo, A. Pathania, S. Parisini, E. Joukov, V. TI Edgetic perturbation of BRCT-mediated interactions caused by the BRCA1 H1686Q sequence variant SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Italian Inst Technol, Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P4-10-01 DI 10.1158/0008-5472.SABCS12-P4-10-01 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704901038 ER PT J AU Desmedt, C Metzger Fumagalli, D Brown, D Singhal, S Vincent, D Adnet, PY Smeets, D Berthed, F Galant, C Salgado, R Veys, I Saini, K Pruneri, G Krop, I Winer, E Michiels, S Piccart, M Lambrechts, D Larsimont, D Viale, G Sotiriou, C AF Desmedt, C. Metzger Fumagalli, D. Brown, D. Singhal, S. Vincent, D. Adnet, P-Y Smeets, D. Berthed, F. Galant, C. Salgado, R. Veys, I. Saini, K. Pruneri, G. Krop, I. Winer, E. Michiels, S. Piccart, M. Lambrechts, D. Larsimont, D. Viale, G. Sotiriou, C. TI Characterization of PIK3CA mutations in lobular breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Inst Jules Bordet, B-1000 Brussels, Belgium. Dana Farber Canc Inst, Boston, MA 02115 USA. VIB, Vesalius Res Ctr, Leuven, Belgium. Inst J Paoli I Calmettes, F-13009 Marseille, France. Catholic Univ Louvain, B-1200 Brussels, Belgium. Univ Milan, European Inst Oncol, Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P3-05-03 DI 10.1158/0008-5472.SABCS12-P3-05-03 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704900461 ER PT J AU Dienstmann, R Vidal, L Dees, EC Chia, S Mayer, EL Porter, D Baney, T Dhuria, S Sen, SK Firestone, B Papoutsakis, D Cameron, S Infante, JR AF Dienstmann, R. Vidal, L. Dees, E. C. Chia, S. Mayer, E. L. Porter, D. Baney, T. Dhuria, S. Sen, S. K. Firestone, B. Papoutsakis, D. Cameron, S. Infante, J. R. TI A phase lb study of LCL161, an oral inhibitor of apoptosis (IAP) antagonist, in combination with weekly paclitaxel in patients with advanced solid tumors SO CANCER RESEARCH LA English DT Meeting Abstract C1 Vail dHebron Univ Hosp, Barcelona, Spain. Hosp Clin Barcelona, Barcelona, Spain. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ British Columbia, British Columbia Canc Agcy, Vancouver, BC V5Z 1M9, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. Novartis Pharmaceut, Cambridge, MA USA. Novartis Pharmaceut, Florham Pk, NJ USA. Sarah Canon Res Inst, Nashville, TN USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P6-11-06 DI 10.1158/0008-5472.SABCS12-P6-11-06 PG 2 WC Oncology SC Oncology GA V43TY UT WOS:000209704902001 ER PT J AU Dieras, V Harbeck, N Budd, GT Greenson, JK Guardino, E Samant, M Chernyukhin, N Smitt, M Krop, IE AF Dieras, V. Harbeck, N. Budd, G. T. Greenson, J. K. Guardino, E. Samant, M. Chernyukhin, N. Smitt, M. Krop, I. E. TI Trastuzumab emtansine in HER2-positive metastatic breast cancer: pooled safety analysis from seven studies SO CANCER RESEARCH LA English DT Meeting Abstract C1 Inst Curie, F-75231 Paris, France. Univ Munich, Breast Ctr, D-81377 Munich, Germany. Cleveland Clin, Lerner Coll Med, Cleveland, OH USA. Univ Michigan, Ann Arbor, MI 48109 USA. Genentech Inc, San Francisco, CA USA. Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P5-18-06 DI 10.1158/0008-5472,SABCS12-P5-18-06 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704901211 ER PT J AU Dowton, AA Meyer, ME Ruddy, KJ Yeh, ED Partridge, AH AF Dowton, A. A. Meyer, M. E. Ruddy, K. J. Yeh, E. D. Partridge, A. H. TI Screening breast magnetic resonance imaging (MRI) in early-stage breast cancer survivors SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P4-01-09 DI 10.1158/0008-5472.SABCS12-P4-01-09 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704900477 ER PT J AU Freedman, RA Pitcher, B Keating, NL Barry, WT Balman, KV Kornblith, A Mandelblatt, J Kimmick, GG Hurria, A Winer, EP Hudis, CA Cohen, HJ Muss, HB AF Freedman, R. A. Pitcher, B. Keating, N. L. Barry, W. T. Balman, K. V. Kornblith, A. Mandelblatt, J. Kimmick, G. G. Hurria, A. Winer, E. P. Hudis, C. A. Cohen, H. J. Muss, H. B. TI Changes in Cognitive Function in Older Women With Breast Cancer Treated with Standard Chemotherapy and Capecitabine within CALGB 49907 SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Med Ctr, Durham, NC USA. Harvard Univ, Sch Med, Boston, MA USA. Mayo Clin, Rochester, MN USA. Georgetown Univ, Washington, DC USA. City Hope Natl Med Ctr, Duarte, CA USA. Mem Sloan Kettering, New York, NY USA. Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P6-08-05 DI 10.1158/0008-5472.SABCS12-P6-08-05 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704901461 ER PT J AU Freedman, RA Gelman, RS Wefel, JS Krop, IE Melisko, ME Ly, A Agar, NYR Connolly, RM Blackwell, KL Nabell, LM Ingle, JN Van Poznak, CH Puhalla, SL Niravath, PA Ryabin, N Wolff, AC Winer, EP Lin, N AF Freedman, R. A. Gelman, R. S. Wefel, J. S. Krop, I. E. Melisko, M. E. Ly, A. Agar, N. Y. R. Connolly, R. M. Blackwell, K. L. Nabell, L. M. Ingle, J. N. Van Poznak, C. H. Puhalla, S. L. Niravath, P. A. Ryabin, N. Wolff, A. C. Winer, E. P. Lin, N. TI TBCRC 022: Phase II Trial of Neratinib for Patients with Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast cancer and Brain Metastases SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Johns Hopkins Univ, Baltimore, MD USA. Duke Univ, Durham, NC USA. Univ Alabama Birmingham, Birmingham, AL USA. Mayo Clin, Rochester, MN USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Pittsburgh, Pittsburgh, PA USA. Baylor, Houston, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA OT1-1-11 DI 10.1158/0008-5472.SABCS12-OT1-1-11 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704900086 ER PT J AU Georgoulia, NE Iliopoulos, D Mitchison, TJ AF Georgoulia, N. E. Iliopoulos, D. Mitchison, T. J. TI Characterization of an exosome-associated apoptosis-inducing activity produced by triple negative breast cancer cells. SO CANCER RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P6-06-02 PG 2 WC Oncology SC Oncology GA V43TY UT WOS:000209704902083 ER PT J AU Goldhirsch, A Piccart-Gebhart, MJ Procter, M de Azambuja, E Weber, HA Untch, M Smith, I Gianni, L Jackisch, C Cameron, D Bell, R Dowsett, M Gelber, RD Leyland-Jones, B Baselga, J AF Goldhirsch, A. Piccart-Gebhart, M. J. Procter, M. de Azambuja, E. Weber, H. A. Untch, M. Smith, I. Gianni, L. Jackisch, C. Cameron, D. Bell, R. Dowsett, M. Gelber, R. D. Leyland-Jones, B. Baselga, J. CA HERA Study Team TI HERA TRIAL: 2 years versus 1 year of trastuzumab after adjuvant chemotherapy in women with HER2-positive early breast cancer at 8 years of median follow up SO CANCER RESEARCH LA English DT Meeting Abstract C1 European Inst Oncol, Milan, Italy. Univ Libre Bruxelles, BrEAST Data Ctr, Inst Jules Bordet, Brussels, Belgium. Frontier Sci Scotland Ltd, Kincraig, Kingussie, Scotland. F Hoffmann La Roche, Basel, Switzerland. Charite, Helios Klinikum Berlin Buch, Akad LK, D-13353 Berlin, Germany. Royal Marsden Hosp, London SW3 6JJ, England. Inst Canc Res, London SW3 6JB, England. Ist Sci San Raffaele, I-20132 Milan, Italy. Klinikum Offenbach, Offenbach, Germany. Univ Edinburgh, Western Gen Hosp, Edinburgh, Midlothian, Scotland. Geelong Hosp, Geelong, Vic, Australia. Royal Marsden NHS Trust, London, England. Dana Farber Canc Inst, Boston, MA 02115 USA. Sanford Res, Sioux Falls, SD USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 4 Z9 4 U1 3 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA S5-2 DI 10.1158/0008-5472.SABCS12-S5-2 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704900022 ER PT J AU Goss, PE Barrios, CH Chan, A Finkelstein, DM Iwata, H Martin, M Braun, A Ke, C Maniar, T Coleman, RE AF Goss, P. E. Barrios, C. H. Chan, A. Finkelstein, D. M. Iwata, H. Martin, M. Braun, A. Ke, C. Maniar, T. Coleman, R. E. TI Denosumab versus placebo as adjuvant treatment for women with early-stage breast cancer at high risk of disease recurrence (D-CARE): An international, randomized, double-blind, placebo-controlled phase 3 clinical trial SO CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. PUCRS Sch Med, Porto Alegre, RS, Brazil. Breast Canc Res Ctr, Perth, WA, Australia. Aichi Canc Ctr, Chikusa Ku, Nagoya, Aichi 464, Japan. Hosp Gregorio Maranon, Madrid, Spain. Amgen Inc, Thousand Oaks, CA 91320 USA. CR UK YCR Sheffield Canc Res Ctr, Sheffield, S Yorkshire, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA OT2-3-03 DI 10.1158/0008-5472.SABCS12-OT2-3-03 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704901084 ER PT J AU Higgins, MJ Chapman, JAW Ingle, JN Sledge, G Budd, GT Ellis, MJ Pritchard, KI Clemons, M Badovinac, CT Han, L Gelmon, K Rabaglio, M Elliott, C Shepherd, LE Goss, PE AF Higgins, M. J. Chapman, J-A W. Ingle, J. N. Sledge, G. Budd, G. T. Ellis, M. J. Pritchard, K. I. Clemons, M. Badovinac, Crnjevic T. Han, L. Gelmon, K. Rabaglio, M. Elliott, C. Shepherd, L. E. Goss, P. E. TI Effect of aspirin (ASP) or celecoxib (CC) use on outcomes in postmenopausal breast cancer patients randomized to adjuvant exemestane or anastrozole: NCIC CTG MA.27 SO CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada. Mayo Clin, Rochester, MN USA. Ottawa Hosp, Ottawa, ON, Canada. Univ Ottawa, Fac Med, Ottawa, ON K1N 6N5, Canada. BCCA, Vancouver Ctr, Vancouver, BC, Canada. Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Cayman Isl, London, England. Indiana Univ, Indianapolis, IN 46204 USA. Cleveland Clin, Cleveland, OH 44106 USA. Washington Univ, St Louis, MO USA. Univ Hosp Bern, Bern, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P2-13-02 DI 10.1158/0008-5472.SABCS12-P2-13-02 PG 2 WC Oncology SC Oncology GA V43TY UT WOS:000209704900261 ER PT J AU Howe, R Omer, Z Hanoch, Y Miron-Shatz, T Thorsen, C Ozanne, EM AF Howe, R. Omer, Z. Hanoch, Y. Miron-Shatz, T. Thorsen, C. Ozanne, E. M. TI Single nucleotide polymorphism testing for breast cancer risk assessment: patient trust and willingness to pay SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Plymouth, Plymouth PL4 8AA, Devon, England. Ono Acad Coll, Kiryat Ono, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P4-11-03 DI 10.1158/0008-5472.SABCS12-P4-11-03 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704901033 ER PT J AU Isakoff, SJ Pulhalla, S Shepherd, SP Falotico, N Kaufman, B Friedlander, M Robson, M Domchek, S Garber, J McKeegan, E Chyla, B Qian, J Giranda, VL AF Isakoff, S. J. Pulhalla, S. Shepherd, S. P. Falotico, N. Kaufman, B. Friedlander, M. Robson, M. Domchek, S. Garber, J. McKeegan, E. Chyla, B. Qian, J. Giranda, V. L. TI A randomized, phase 2 study of the poly (ADP-ribose) polymerase (PARP) inhibitor veliparib (ABT-888) in combination with temozolomide (TMZ) or in combination with carboplatin (C) and paclitaxel (P) versus placebo plus C/P in subjects with BRCA1 or BRACA2 mutation and metastatic breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Abbott Labs, Abbott Pk, IL 60064 USA. Chaim Sheba Med Ctr, Tel Hashomer, Israel. Prince Wales Hosp, Sydney, NSW, Australia. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Penn, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA OT2-3-07 DI 10.1158/0008-5472.SABCS12-OT2-3-07 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704901088 ER PT J AU Isakoff, SJ Goss, PE Mayer, EL Traina, T Carey, LA Krag, KJ Liu, MC Rugo, H Stearns, V Come, S Finkelstein, D Hartman, AR Garber, JE Ryan, PD Winer, EP Ellisen, LW AF Isakoff, S. J. Goss, P. E. Mayer, E. L. Traina, T. Carey, L. A. Krag, K. J. Liu, M. C. Rugo, H. Stearns, V. Come, S. Finkelstein, D. Hartman, A-R Garber, J. E. Ryan, P. D. Winer, E. P. Ellisen, L. W. TI Impact of BRCA1/2 Mutation Status in TBCRC009: A multicenter phase II study of cisplatin or carboplatin for metastatic triple negative breast cancer. SO CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Mass Gen North Shore Canc Ctr, Danvers, MA USA. Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Myriad Genet, Salt Lake City, UT USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA PD09-03 DI 10.1158/0008-5472.SABCS12-PD09-03 PG 2 WC Oncology SC Oncology GA V43TY UT WOS:000209704901420 ER PT J AU Jacene, H DiPiro, P Belion, J Nakhlis, F Hirshfield-Bartek, J Yeh, E Overmoyer, B AF Jacene, H. DiPiro, P. Belion, J. Nakhlis, F. Hirshfield-Bartek, J. Yeh, E. Overmoyer, B. TI Discrepancy between CT and FDG-PET/CT in the staging of patients with inflammatory breast cancer: Implications for radiation therapy treatment planning SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Jacene, H.; DiPiro, P.; Belion, J.; Nakhlis, F.; Hirshfield-Bartek, J.; Yeh, E.; Overmoyer, B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P5-02-01 DI 10.1158/0008-5472.SABCS12-P5-02-01 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704901162 ER PT J AU Jeselsohn, RM Regan, MM Werner, L Fatima, A He, HH Brown, M Iglehart, JD Richardson, AL Come, S AF Jeselsohn, R. M. Regan, M. M. Werner, L. Fatima, A. He, H. H. Brown, M. Iglehart, J. D. Richardson, A. L. Come, S. TI Inflammatory gene expression variations in the interval between core needle biopsy and excisional biopsy in early breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P1-07-07 DI 10.1158/0008-5472.SABCS12-P1-07-07 PG 2 WC Oncology SC Oncology GA V43TY UT WOS:000209704902139 ER PT J AU Juric, D Argiles, G Burns, HA Gonzalez-Angulo, AM Saura, C Quadt, C Douglas, M Demanse, D De Buck, S Baselga, J AF Juric, D. Argiles, G. Burns, H. A. Gonzalez-Angulo, A. M. Saura, C. Quadt, C. Douglas, M. Demanse, D. De Buck, S. Baselga, J. TI Phase I study of BYL719, an alpha-specific PI3K inhibitor, in patients with PIK3CA mutant advanced solid tumors: preliminary efficacy and safety in patients with PIK3CA mutant ER -positive (ER plus ) metastatic breast cancer (MBC) SO CANCER RESEARCH LA English DT Meeting Abstract C1 Massachussetts Gen Hosp, Ctr Canc, Boston, MA USA. Vall dHebron Univ Hosp, Barcelona, Spain. Sarah Cannon Res Inst, Nashville, TN USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Novartis Pharma Corp, E Hanover, NJ USA. Novartis Pharma AG, Basel, Switzerland. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P8-10-07 DI 10.1158/0008-5472.SABCS12-P8-10-07 PG 2 WC Oncology SC Oncology GA V43TY UT WOS:000209704902018 ER PT J AU Karp, JE Blackford, A Visvanathan, K Rugo, HS Moy, B Goldstein, LJ Stockerl-Goldstein, K Neumayer, L Langbaum, TS Hughes, ME Weeks, JC Wolff, AC AF Karp, J. E. Blackford, A. Visvanathan, K. Rugo, H. S. Moy, B. Goldstein, L. J. Stockerl-Goldstein, K. Neumayer, L. Langbaum, T. S. Hughes, M. E. Weeks, J. C. Wolff, A. C. TI Myelodysplatic syndrome and/or acute myelogenous leukemia (MDS and/or AML) after a breast cancer diagnosis: the National Comprehensive Cancer Network (NCCN) experience. SO CANCER RESEARCH LA English DT Meeting Abstract C1 Johns Hopkins Kimmel Canc Ctr, Baltimore, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Washington Univ, Sch Med, St Louis, MO 63130 USA. Univ Utah, Sch Med, Salt Lake City, UT 84112 USA. Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 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 DEC 15 PY 2012 VL 72 SU 24 MA S3-5 DI 10.1158/0008-5472.SABCS12-S3-5 PG 2 WC Oncology SC Oncology GA V43TY UT WOS:000209704900010 ER PT J AU Kodack, DP Chung, E Yamashita, H Incio, J Peters, A Song, Y Ager, E Huang, Y Farrar, C Lussiez, A Goel, S Snuderl, M Kamoun, W Hiddingh, L Tannous, BA Fukumura, D Engelman, JA Jain, RK AF Kodack, D. P. Chung, E. Yamashita, H. Incio, J. Peters, A. Song, Y. Ager, E. Huang, Y. Farrar, C. Lussiez, A. Goel, S. Snuderl, M. Kamoun, W. Hiddingh, L. Tannous, B. A. Fukumura, D. Engelman, J. A. Jain, R. K. TI Combined targeting of HER2 and VEGFR2 for effective treatment of HER2-amplified breast cancer brain metastases. SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Kodack, D. P.; Chung, E.; Yamashita, H.; Incio, J.; Peters, A.; Song, Y.; Ager, E.; Huang, Y.; Farrar, C.; Lussiez, A.; Goel, S.; Snuderl, M.; Kamoun, W.; Hiddingh, L.; Tannous, B. A.; Fukumura, D.; Engelman, J. A.; Jain, R. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P3-12-03 DI 10.1158/0008-5472.SABCS12-P3-12-03 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704900418 ER PT J AU Kvale, EA Azuero, CB Azuero, A Fisch, M Ritchie, C AF Kvale, E. A. Azuero, C. B. Azuero, A. Fisch, M. Ritchie, C. TI Use of the MD Anderson Symptom Inventory to Screen for Depression in Breast Cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Birmingham VA Med Ctr, Birmingham, AL USA. Univ Alabama Birmingham, Birmingham, AL USA. Univ Alabama, Tuscaloosa, AL USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P2-12-14 DI 10.1158/0008-5472.SABCS12-P2-12-14 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704900239 ER PT J AU Lim, E He, HH Chi, D Yeung, TY Schnitt, S Liu, SX Garber, J Richardson, A Brown, M AF Lim, E. He, H. H. Chi, D. Yeung, T. Y. Schnitt, S. Liu, S. X. Garber, J. Richardson, A. Brown, M. TI Differences in estrogen receptor signaling in non-malignant primary ER-positive breast epithelial cells and breast cancer. SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA PD01-08 DI 10.1158/0008-5472.SABCS12-PD01-08 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704901356 ER PT J AU Lin, N Danso, MA David, AK Muscato, J Rayson, D Houck, WA Ellis, C DeSilvio, M Garofalo, A Nagarwala, Y Winer, E AF Lin, N. Danso, M. A. David, A. K. Muscato, J. Rayson, D. Houck, W. A., III Ellis, C. DeSilvio, M. Garofalo, A. Nagarwala, Y. Winer, E. TI Human epidermal growth factor receptor 2 (HER2) suppression with the addition of lapatinib to trastuzumab in HER2-positive metastatic breast cancer (LTP112515) SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Virginia Oncol Associates, Norfolk, VA USA. Augusta Oncol Associates, Augusta, GA USA. Missouri Canc Associates, Columbia, MO USA. QEII Hlth Sci Ctr, Halifax, NS, Canada. Virginia Canc Specialists PC, Winchester, VA USA. GlaxoSmithKline Oncol, Collegeville, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA OT1-1-07 DI 10.1158/0008-5472.SABCS12-OT1-1-07 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704900082 ER PT J AU Lin, NU Schwartzberg, LS Kesari, S Yardley, DA Verma, S Anders, CK Shih, T Shen, Y Miller, K AF Lin, N. U. Schwartzberg, L. S. Kesari, S. Yardley, D. A. Verma, S. Anders, C. K. Shih, T. Shen, Y. Miller, K. TI A phase 2, multi-center, open label study evaluating the efficacy and safety of GRN1005 alone or in combination with trastuzumab in patients with brain metastases from breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Calif San Diego, La Jolla, CA USA. Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. West Clin, Memphis, TN USA. Geron, Menlo Pk, CA USA. Univ N Carolina, Chapel Hill, NC USA. Sarah Cannon Res Inst, Nashville, TN USA. Tennessee Oncol PLLC, Nashville, TN USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P3-12-04 DI 10.1158/0008-5472.SABCS12-P3-12-04 PG 2 WC Oncology SC Oncology GA V43TY UT WOS:000209704900419 ER PT J AU Liu, MC Pitcher, BN Mardis, ER Davies, SR Snider, JE Vickery, T Reed, JP DeSchryver, K Singh, B Friedman, PN Gradishar, WJ Perez, EA Martino, S Citron, ML Norton, L Winer, EP Hudis, CA Perou, CM Ellis, MJ Barry, WT AF Liu, M. C. Pitcher, B. N. Mardis, E. R. Davies, S. R. Snider, J. E. Vickery, T. Reed, J. P. DeSchryver, K. Singh, B. Friedman, P. N. Gradishar, W. J. Perez, E. A. Martino, S. Citron, M. L. Norton, L. Winer, E. P. Hudis, C. A. Perou, C. M. Ellis, M. J. Barry, W. T. TI PAM50 gene signature is prognostic for breast cancer patients treated with adjuvant anthracycline and taxane based chemotherapy SO CANCER RESEARCH LA English DT Meeting Abstract C1 Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. Duke Univ, Med Ctr, Durham, NC USA. Washington Univ, St Louis, MO USA. Washington Univ, Sch Med, St Louis, MO USA. NYU, Med Ctr, New York, NY 10016 USA. Univ Chicago, Chicago, IL 60637 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Feinberg Sch Med, Chicago, IL 60611 USA. Mayo Clin, Jacksonville, FL 32224 USA. Angeles Clin & Res Inst, Santa Monica, CA USA. ProHLTH Care Associates, Hofstra North Shore LIJ Sch Med, Lake Success, NY USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P2-10-01 DI 10.1158/0008-5472.SABCS12-P2-10-01 PG 2 WC Oncology SC Oncology GA V43TY UT WOS:000209704900204 ER PT J AU Mayer, EL Miller, K O'Shaughnessy, J Dickler, M Vogel, C Leyland-Jones, B Steelman, L Robinson, M Kuriyama, N Agarwal, S AF Mayer, E. L. Miller, K. O'Shaughnessy, J. Dickler, M. Vogel, C. Leyland-Jones, B. Steelman, L. Robinson, M. Kuriyama, N. Agarwal, S. TI Tivozanib in combination with paclitaxel vs placebo with paclitaxel in patients with locally advanced or metastatic triple-negative breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA 02115 USA. Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. Texas Oncol, Baylor A Charles Sammons Canc Ctr, Dallas, TX USA. US Oncol, Dallas, TX USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Sylvester Comprehens Canc Ctr, Miami, FL USA. Sanford Res USD, Sioux Falls, SD USA. AVEO Oncol, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA OT2-3-11 DI 10.1158/0008-5472.5ABCS12-OT2-3-11 PG 2 WC Oncology SC Oncology GA V43TY UT WOS:000209704901092 ER PT J AU Mayer, IA Abramson, VG Balko, JM Isakoff, SJ Forero, A Kuba, MG Sanders, ME Li, Y Winer, E Arteaga, CL AF Mayer, I. A. Abramson, V. G. Balko, J. M. Isakoff, S. J. Forero, A. Kuba, M. G. Sanders, M. E. Li, Y. Winer, E. Arteaga, C. L. TI P6-10-05: SU2C Phase 1 b Trial of Dual mTOR Inhibitor BEZ235 with Letrozole in ER+/HER2-Metastatic Breast Cancer (MBC) SO CANCER RESEARCH LA English DT Meeting Abstract C1 Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Massachussets Gen Hosp, Boston, MD USA. Univ Alabama Birmingham, Birmingham, AL USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 DI 10.1158/0008-5472.SABCS12-P6-10-05 PG 2 WC Oncology SC Oncology GA V43TY UT WOS:000209704902015 ER PT J AU Miles, D Baselga, J Amadori, D Sunpaweravong, P Semiglazov, V Knott, A Clark, E Ross, G Swain, SM AF Miles, D. Baselga, J. Amadori, D. Sunpaweravong, P. Semiglazov, V. Knott, A. Clark, E. Ross, G. Swain, S. M. TI Pertuzumab (P) in combination with trastuzumab (T) and docetaxel (D) in elderly patients with HER2-positive metastatic breast cancer in the CLEOPATRA study SO CANCER RESEARCH LA English DT Meeting Abstract C1 Mt Vernon Canc Ctr, Northwood, Middx, England. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Ist Sci Romagnolo Studio & Cura Tumori IRST, Meldola, Italy. Prince Songkla Univ, Songklanagarind Hosp, Hat Yai, Thailand. NN Petrov Res Inst Oncol, St Petersburg, Russia. Roche Prod Ltd, Welwyn Garden City, England. MedStar Washington Hosp Ctr, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P5-18-01 DI 10.1158/0008-5472.SABCS12-P5-18-01 PG 2 WC Oncology SC Oncology GA V43TY UT WOS:000209704901241 ER PT J AU Miller, KD O'Neill, A Dang, C Northfelt, D Gradishar, W Sledge, GW AF Miller, K. D. O'Neill, A. Dang, C. Northfelt, D. Gradishar, W. Sledge, G. W. TI Bevacizumab (B) in the adjuvant treatment of breast cancer - first toxicity results from Eastern Cooperative Oncology Group trial E5103. SO CANCER RESEARCH LA English DT Meeting Abstract C1 Indiana Univ, Melvin & Bren Simon Canc Ctr, Bloomington, IN 47405 USA. Dana Farber Canc Inst, Boston, MA USA. Mem Sloan Kettering Canc Ctr, New York, NY USA. Mayo Clin, Rochester, MN USA. Northwestern Univ, Evanston, IL 60208 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P5-17-01 DI 10.1158/0008-5472.SABCS12-P5-17-01 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704901200 ER PT J AU Overmoyer, BA Almendro, V Shu, S Peluffo, G Park, SY Nakhlis, F Bellon, JR Yeh, ED Jacene, HA Hirshfield-Bartek, J Polyak, K AF Overmoyer, B. A. Almendro, V. Shu, S. Peluffo, G. Park, S. Y. Nakhlis, F. Bellon, J. R. Yeh, E. D. Jacene, H. A. Hirshfield-Bartek, J. Polyak, K. TI JAK2/STAT3 activity in inflammatory breast cancer supports the investigation of JAK2 therapeutic targeting SO CANCER RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Seoul Natl Univ, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P4-06-01 DI 10.1158/0008-5472.SABCS12-P4-06-01 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704901182 ER PT J AU Perez, EA Eckel-Passow, JE Balman, KV Anderson, SK Thompson, EA Asmann, YW Jen, J Dueck, AC Lingle, WL Sledge, GW Winer, EP Gralow, J Jenkins, RB Reinholz, MM AF Perez, E. A. Eckel-Passow, J. E. Balman, K. V. Anderson, S. K. Thompson, E. A. Asmann, Y. W. Jen, J. Dueck, A. C. Lingle, W. L. Sledge, G. W. Winer, E. P. Gralow, J. Jenkins, R. B. Reinholz, M. M. TI Predictive genomic markers to chemotherapy and adjuvant trastuzumab via whole genome expression DASL profiling in the N9831 adjuvant study SO CANCER RESEARCH LA English DT Meeting Abstract C1 Mayo Clin, Jacksonville, FL 32224 USA. Mayo Clin, Rochester, MN USA. Mayo Clin, Scottsdale, AZ USA. Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Seattle Canc Care Alliance, Seattle, WA USA. Ventana Med Syst Inc, Tucson, AZ USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA PD10-04 DI 10.1158/0008-5472.SABCS12-PD10-04 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704901431 ER PT J AU Piccart, M Baselga, J Noguchi, S Burris, H Gnant, M Hortobagyi, G Mukhopadhyay, P Taran, T Sahmoud, T Rugo, H AF Piccart, M. Baselga, J. Noguchi, S. Burris, H. Gnant, M. Hortobagyi, G. Mukhopadhyay, P. Taran, T. Sahmoud, T. Rugo, H. TI Final progression-free survival analysis of BOLERO-2: a phase Ill trial of everolimus for postmenopausal women with advanced breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Libre Bruxelles, Inst Jules Bordet, Brussels, Belgium. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Osaka Univ, Osaka, Japan. Sarah Cannon Res Inst, Nashville, TN USA. Med Univ Vienna, Ctr Comprehens Canc, Vienna, Austria. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Novartis Pharmaceut, E Hanover, NJ USA. Univ Calif San Francisco, San Francisco Helen Diller Family Comprehens Canc, San Francisco, CA 94143 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P6-04-02 DI 10.1158/0008-5472.SABCS12-126-04-02 PG 2 WC Oncology SC Oncology GA V43TY UT WOS:000209704902068 ER PT J AU Regan, MM Dafni, U Karlis, D Goldhirsch, A Untch, M Smith, I Gianni, L Jackisch, C de Azambuja, E Heinzmann, D Cameron, D Bell, R Dowsett, M Baselga, J Leyland-Jones, B Piccart-Gebhart, MJ Gelber, RD AF Regan, M. M. Dafni, U. Karlis, D. Goldhirsch, A. Untch, M. Smith, I. Gianni, L. Jackisch, C. de Azambuja, E. Heinzmann, D. Cameron, D. Bell, R. Dowsett, M. Baselga, J. Leyland-Jones, B. Piccart-Gebhart, M. J. Gelber, R. D. CA HERA Study Team TI Selective Crossover in Randomized Trials of Adjuvant Trastuzumab for Breast Cancer: Coping with Success SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Athens, Athens, Greece. Frontier Sci Fdn Hellas, Athens, Greece. Univ Libre Bruxelles, Inst Jules Bordet, Brussels, Belgium. Helios Klinikum Berlun Buch, Berlin, Germany. Royal Marsden Hosp, London SW3 6JJ, England. Inst Canc Res, London SW3 6JB, England. San Raffaele Inst, Milan, Italy. Western Gen Hosp, Edinburgh, Midlothian, Scotland. Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland. Royal Marsden NHS Trust, London, England. European Inst Oncol, Milan, Italy. Athens Univ Econ, Athens, Greece. Massachusetts Gen Hosp, Boston, MA 02114 USA. F Hoffmann La Roche, Basel, Switzerland. Sanford Res, Sioux Falls, SD USA. Geelong Hosp, Andrew Love Canc Ctr, Geelong, Vic, Australia. Klinikum Offenbach, Offenbach, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P5-18-02 DI 10.1158/0008-5472.SABCS12-P5-18-02 PG 2 WC Oncology SC Oncology GA V43TY UT WOS:000209704901242 ER PT J AU Romond, E Suman, VJ Jeong, JH Sledge, GW Geyer, CE Martino, S Rastogi, P Gralow, J Swain, SM Winer, E Colon-Otero, G Hudis, C Paik, S Davidson, N Mamounas, EP Zujewski, JA Wolmark, N Perez, EA AF Romond, E. Suman, V. J. Jeong, J-H Sledge, G. W., Jr. Geyer, C. E., Jr. Martino, S. Rastogi, P. Gralow, J. Swain, S. M. Winer, E. Colon-Otero, G. Hudis, C. Paik, S. Davidson, N. Mamounas, E. P. Zujewski, J. A. Wolmark, N. Perez, E. A. CA Natl Surg Adjuvant Breast Bowel Pr TI Trastuzumab plus adjuvant chemotherapy for HER2-positive breast cancer: Final planned joint analysis of overall survival (OS) from NSABP B-31 and NCCTG N9831 SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Kentucky, Lexington, KY 40506 USA. Mayo Clin, Rochester, MN USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. IU Simon Canc Ctr, Indianapolis, IN USA. Univ Texas Southwestern Med Ctr, Dallas, TX USA. Angeles Clin & Res Inst, Santa Monica, CA USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA. Univ Washington, Seattle, WA 98195 USA. Medstar Washington Hosp Ctr, Washington, DC USA. Dana Farber Canc Inst, Boston, MA USA. Mem Sloan Kettering Canc Ctr, New York, NY USA. Aultman Hosp, Canton, OH USA. NCI, Canc Therapy Evaluat Program, NIH, DHHS, Bethesda, MD 20892 USA. Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 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 DEC 15 PY 2012 VL 72 SU 24 MA S5-5 DI 10.1158/0008-5472.SABCS12-S5-5 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704900026 ER PT J AU Rye, IH Helland, A Saetersdal, A Naume, B Almendro, V Polyak, K Boressen-Dale, AL Russnes, HG AF Rye, I. H. Helland, A. Saetersdal, A. Naume, B. Almendro, V. Polyak, K. Boressen-Dale, A-L Russnes, H. G. TI Intra-tumor heterogeneity as a predictor of therapy response in HER2 positive breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Inst Canc Res, Oslo, Norway. Oslo Univ Hosp, Oslo, Norway. Univ Oslo, Oslo, Norway. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Hosp Clin Barcelona, Barcelona, Spain. NR 0 TC 1 Z9 1 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P3-05-04 DI 10.1158/0008-5472.SABCS12-P3-05-04 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704900462 ER PT J AU Saura, C Lin, N Ciruelos, E Maurer, M Lluch, A Gavila, J Winer, E Baselga, J Rodon, J AF Saura, C. Lin, N. Ciruelos, E. Maurer, M. Lluch, A. Gavila, J. Winer, E. Baselga, J. Rodon, J. TI A phase II, non-randomized, multicenter, exploratory trial of single agent BKM120 in patients with triple negative metastatic breast cancer. SO CANCER RESEARCH LA English DT Meeting Abstract C1 Vall dHebron Univ Hosp, Barcelona, Spain. Dana Farber Canc Inst, Boston, MA 02115 USA. Hosp 12 Octubre, E-28041 Madrid, Spain. Columbia Univ, Med Ctr, New York, NY USA. Hosp Clin Valencia, Valencia, Spain. Inst Valenciano Oncol, Valencia, Spain. Massachusetts Gen Hosp, Boston, MA 02114 USA. SOLTI Breast Canc Res Grp, Barcelona, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA OT2-3-06 DI 10.1158/0008-5472.5ABCS12-OT2-3-06 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704901087 ER PT J AU Seah, DS Lin, NU Curley, C Winer, E Partridge, A AF Seah, D. S. Lin, N. U. Curley, C. Winer, E. Partridge, A. TI Informational needs and psychosocial assessment of patients in their first year after metastatic breast cancer diagnosis SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Seah, D. S.; Lin, N. U.; Curley, C.; Winer, E.; Partridge, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P6-08-03 DI 10.1158/0008-5472.SABCS12-P6-08-03 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704901458 ER PT J AU Seah, DS Scott, SM Najita, J Openshaw, T Krag, KJ Frank, E Sohl, J Stadler, ZK Garrett, M Winer, EP Come, S Lin, NU AF Seah, D. S. Scott, S. M. Najita, J. Openshaw, T. Krag, K. J. Frank, E. Sohl, J. Stadler, Z. K. Garrett, M. Winer, E. P. Come, S. Lin, N. U. TI Attitudes of metastatic breast cancer patients towards research biopsies SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Isreal Deaconness Med Ctr, Boston, MA USA. Canc Care Maine, Brewer, ME USA. Mass Gen North Shore Canc Ctr, Danvers, MA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P2-16-04 DI 10.1158/0008-5472.SABCS12-P2-16-04 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704900285 ER PT J AU Sgroi, DC Sestak, I Zhang, Y Erlander, MG Schnabel, CA Goss, PE Cuzick, J Dowsett, M AF Sgroi, D. C. Sestak, I. Zhang, Y. Erlander, M. G. Schnabel, C. A. Goss, P. E. Cuzick, J. Dowsett, M. TI Evaluation of Prognostic and Predictive Performance of Breast Cancer Index and Its Components in Hormonal Receptor-Positive Breast Cancer Patients: A TransATAC Study SO CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Queen Mary Univ, London, England. BioTheranostics Inc, San Diego, CA USA. Royal Marsden Hosp, London SW3 6JJ, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P2-10-15 DI 10.1158/0008-5472.SABCS12-P2-10-15 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704900219 ER PT J AU Sgroi, DC Sestak, I Cuzick, J Zhang, Y Schnabel, CA Erlander, MG Goss, PE Dowsett, M AF Sgroi, D. C. Sestak, I. Cuzick, J. Zhang, Y. Schnabel, C. A. Erlander, M. G. Goss, P. E. Dowsett, M. TI Comparative Performance of Breast Cancer Index (BCI) vs. Oncotype Dx and IHC4 in the Prediction of Late Recurrence in Hormonal Receptor-Positive Lymph Node-Negative Breast Cancer Patients: A TransATAC Study SO CANCER RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Queen Mary Univ, Ctr Canc Prevent, London, England. BioTheranostics Inc, San Diego, CA USA. Royal Marsden Hosp, Breakthrough Breast Canc Ctr, London SW3 6JJ, England. NR 0 TC 8 Z9 8 U1 0 U2 0 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 DEC 15 PY 2012 VL 72 SU 24 MA S1-9 DI 10.1158/0008-5472.SABCS12-S1-9 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704900068 ER PT J AU Skolny, MN Miller, CL Shenouda, M Jammallo, LS O'Toole, J Niemierko, A Taghian, AG AF Skolny, M. N. Miller, C. L. Shenouda, M. Jammallo, L. S. O'Toole, J. Niemierko, A. Taghian, A. G. TI The Association of Low Level Arm Volume Increases with Lymphedema Symptoms Following Treatment for Breast Cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Skolny, M. N.; Miller, C. L.; Shenouda, M.; Jammallo, L. S.; O'Toole, J.; Niemierko, A.; Taghian, A. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P6-09-04 DI 10.1158/0008-5472.SABCS12-P6-09-04 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704901471 ER PT J AU Sninsky, J Wang, A Gray, K Lagier, R Christopherson, C Rowland, C Chang, M Kammler, R Viale, G Kwok, S Regan, M Leyland-Jones, B AF Sninsky, J. Wang, A. Gray, K. Lagier, R. Christopherson, C. Rowland, C. Chang, M. Kammler, R. Viale, G. Kwok, S. Regan, M. Leyland-Jones, B. TI Predictive value of a proliferation score (MS) in postmenopausal women with endocrine-responsive breast cancer: results from International Breast Cancer Study Group (IBCSG) Trial IX SO CANCER RESEARCH LA English DT Meeting Abstract C1 Celera, Alameda, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. IBCSG Coordinating Ctr, Bern, Switzerland. European Inst Oncol, Milan, Italy. Sanford Res, Sioux Falls, SD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA PD10-03 DI 10.1158/0008-5472.SABCS12-PD10-03 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704901430 ER PT J AU Swain, SM Kim, SB Cortes, J Ro, J Semiglazov, V Campone, M Ciruelos, E Ferrero, JM Schneeweiss, A Knott, A Clark, E Ross, G Benyunes, MC Baselga, J AF Swain, S. M. Kim, S-B Cortes, J. Ro, J. Semiglazov, V. Campone, M. Ciruelos, E. Ferrero, J-M Schneeweiss, A. Knott, A. Clark, E. Ross, G. Benyunes, M. C. Baselga, J. TI Confirmatory overall survival (OS) analysis of CLEOPATRA: a randomized, double-blind, placebo-controlled Phase Ill study with pertuzumab (P), trastuzumab (T), and docetaxel (D) in patients (pts) with HER2-positive first-line (1L) metastatic breast cancer (MBC) SO CANCER RESEARCH LA English DT Meeting Abstract C1 MedStar Washington Hosp Ctr, Washington, DC USA. Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea. Vall dHebron Univ Hosp, Barcelona, Spain. Natl Canc Ctr, Goyang, South Korea. NN Petrov Res Inst Oncol, St Petersburg, Russia. Ctr Rene Gauducheau, F-44035 Nantes, France. Hosp 12 Octubre, E-28041 Madrid, Spain. Ctr Antoine Lacassagne, F-06054 Nice, France. Univ Heidelberg Hosp, Heidelberg, Germany. Roche Prod Ltd, Welwyn Garden City, England. Genentech Inc, San Francisco, CA 94080 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 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 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P5-18-26 DI 10.1158/0008-5472.SABCS12-P5-18-26 PG 2 WC Oncology SC Oncology GA V43TY UT WOS:000209704901233 ER PT J AU Taghian, AG Skolny, MN O'Toole, J Miller, CL Jammallo, LS Specht, MC AF Taghian, A. G. Skolny, M. N. O'Toole, J. Miller, C. L. Jammallo, L. S. Specht, M. C. TI The PREDICT Study (Prospective, Randomized Early Detection and Intervention after Breast Cancer-Treatment, for women at risk of lymphedema) SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Taghian, A. G.; Skolny, M. N.; O'Toole, J.; Miller, C. L.; Jammallo, L. S.; Specht, M. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC 15 PY 2012 VL 72 SU 24 MA OT3-2-02 DI 10.1158/0008-5472.SABCS12-OT3-2-02 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704901347 ER PT J AU Tao, J Ip, P Auricchio, N Juric, D Yu, M Shyamala, M Kim, P Singh, S Hazra, S Haber, D Scaltriti, M Baselga, J AF Tao, J. Ip, P. Auricchio, N. Juric, D. Yu, M. Shyamala, M. Kim, P. Singh, S. Hazra, S. Haber, D. Scaltriti, M. Baselga, J. TI Combined Blockade of PI3K/AKT and EGFR/HER3 Enhances Anti-Tumor Activity in Triple Negative Breast Cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA S5-7 DI 10.1158/0008-5472.SABCS12-S5-7 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704900028 ER PT J AU Vandergrift, JL Breslin, TM Niland, JC Edge, SB Wolff, AC Marcom, PK Rugo, HS Moy, B Wilson, JL Ottesen, RA Weeks, JC Wong, YN AF Vandergrift, J. L. Breslin, T. M. Niland, J. C. Edge, S. B. Wolff, A. C. Marcom, P. K. Rugo, H. S. Moy, B. Wilson, J. L. Ottesen, R. A. Weeks, J. C. Wong, Y-N TI The association between timing in adjuvant chemotherapy administration and overall survival for women with breast cancer within the National Comprehensive Cancer Network (NCCN) SO CANCER RESEARCH LA English DT Meeting Abstract C1 Natl Comprehens Canc Network, Ft Washington, MD USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. City Hope Natl Med Ctr, Ctr Comprehens Canc, Duarte, CA USA. Dana Farber Brigham Womens Canc Ctr, Boston, MA USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Duke Canc Inst, Durham, NC USA. UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. James Canc Hosp, Columbus, OH USA. Solove Res Inst, Columbus, OH USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P1-13-05 DI 10.1158/0008-5472.SABCS12-P1-13-05 PG 2 WC Oncology SC Oncology GA V43TY UT WOS:000209704902151 ER PT J AU Vaz-Luis, I Seah, D Olson, E Metzger, O Wagle, N Sohl, J Litsas, G Burstein, H Krop, I Winer, E Lin, NU AF Vaz-Luis, I. Seah, D. Olson, E. Metzger, O. Wagle, N. Sohl, J. Litsas, G. Burstein, H. Krop, I. Winer, E. Lin, N. U. TI Clinicopathological features among patients with HER2-positive breast cancer with prolonged response to trastuzumab based therapy SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Ohio State Univ, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P5-18-03 DI 10.1158/0008-5472.SABCS12-P5-18-03 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704901243 ER PT J AU Warren, LE Regan, MM Nakhlis, F Yeh, ED Jacene, HA Hirshfield-Bartek, J Overmoyer, BA Belton, JR AF Warren, L. E. Regan, M. M. Nakhlis, F. Yeh, E. D. Jacene, H. A. Hirshfield-Bartek, J. Overmoyer, B. A. Belton, J. R. TI Patterns of failure in patients with inflammatory breast cancer: the case for aggressive local/regional treatment SO CANCER RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P3-10-06 DI 10.1158/0008-5472.SABCS12-P3-10-06 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704900437 ER PT J AU Yu, M Bardia, A Wittner, BS Stott, SL Smas, ME Ting, DT Isakoff, SJ Ciciliano, JC Wells, MN Shah, AM Concannon, KF Sequist, LV Brachtel, E Sgroi, D Baselga, J Ramaswamy, S Toner, M Haber, DA Maheswaran, S AF Yu, M. Bardia, A. Wittner, B. S. Stott, S. L. Smas, M. E. Ting, D. T. Isakoff, S. J. Ciciliano, J. C. Wells, M. N. Shah, A. M. Concannon, K. F. Sequist, L. V. Brachtel, E. Sgroi, D. Baselga, J. Ramaswamy, S. Toner, M. Haber, D. A. Maheswaran, S. TI circulating tumor cells in breast cancer exhibit dynamic changes in epithelial and mesenchymal cell composition SO CANCER RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. Howard Hughes Med Inst, Chevy Chase, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2012 VL 72 SU 24 MA P2-01-14 DI 10.1158/0008-5472.SABCS12-P2-01-14 PG 1 WC Oncology SC Oncology GA V43TY UT WOS:000209704900201 ER PT J AU Bartzokis, G Lu, PH Heydari, P Couvrette, A Lee, GJ Kalashyan, G Freeman, F Grinstead, JW Villablanca, P Finn, JP Mintz, J Alger, JR Altshuler, LL AF Bartzokis, George Lu, Po H. Heydari, Panthea Couvrette, Alexander Lee, Grace J. Kalashyan, Greta Freeman, Frank Grinstead, John W. Villablanca, Pablo Finn, J. Paul Mintz, Jim Alger, Jeffry R. Altshuler, Lori L. TI Multimodal Magnetic Resonance Imaging Assessment of White Matter Aging Trajectories Over the Lifespan of Healthy Individuals SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Aging; Alzheimer; axial diffusivity; cognition; degeneration; diffusion tensor imaging (DTI); development; fractional anisotropy; magnetic resonance imaging (MRI); myelin; oligodendrocytes; radial diffusivity; relaxation rate (R-2); white matter (WM) ID MYELINATED NERVE-FIBERS; PRIMARY VISUAL-CORTEX; T2 RELAXATION-TIME; ALZHEIMERS-DISEASE; RHESUS-MONKEY; STRUCTURAL INTEGRITY; RADIAL DIFFUSIVITY; COGNITIVE FUNCTION; BRAIN MATURATION; PROCESSING SPEED AB Background: Postmortem and volumetric imaging data suggest that brain myelination is a dynamic lifelong process that, in vulnerable late-myelinating regions, peaks in middle age. We examined whether known regional differences in axon size and age at myelination influence the timing and rates of development and degeneration/repair trajectories of white matter (WM) microstructure biomarkers. Methods: Healthy subjects (n = 171) 14-93 years of age were examined with transverse relaxation rate (R-2) and four diffusion tensor imaging measures (fractional anisotropy [FA] and radial, axial, and mean diffusivity [RD, AxD, MD, respectively]) of frontal lobe, genu, and splenium of the corpus callosum WM (FWM, GWM, and SWM, respectively). Results: Only R-2 reflected known levels of myelin content with high values in late-myelinating FWM and GWM regions and low ones in early-myelinating SWM. In FWM and GWM, all metrics except FA had significant quadratic components that peaked at different ages (R-2 < RD < MD < AxD), with FWM peaking later than GWM. Factor analysis revealed that, although they defined different factors, R-2 and RD were the metrics most closely associated with each other and differed from AxD, which entered into a third factor. Conclusions: The R-2 and RD trajectories were most dynamic in late-myelinating regions and reflect age-related differences in myelination, whereas AxD reflects axonal size and extra-axonal space. The FA and MD had limited specificity. The data suggest that the healthy adult brain undergoes continual change driven by development and repair processes devoted to creating and maintaining synchronous function among neural networks on which optimal cognition and behavior depend. C1 [Bartzokis, George; Heydari, Panthea; Couvrette, Alexander; Kalashyan, Greta; Freeman, Frank; Altshuler, Lori L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90095 USA. [Bartzokis, George] Univ Calif Los Angeles, David Geffen Sch Med, Lab Neuroimaging, Los Angeles, CA 90095 USA. [Lu, Po H.; Lee, Grace J.; Alger, Jeffry R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Villablanca, Pablo; Finn, J. Paul] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol, Los Angeles, CA 90095 USA. [Bartzokis, George] Greater Los Angeles Vet Adm Healthcare Syst, Los Angeles, CA USA. [Grinstead, John W.] Siemens Healthcare, Portland, OR USA. [Mintz, Jim] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. RP Bartzokis, G (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, 300 UCLA Med Plaza, Los Angeles, CA 90095 USA. EM gbar@ucla.edu RI Bartzokis, George/K-2409-2013 FU National Institutes of Health [MH0266029, AG027342, K23-AG028727]; Risk Control Strategies Inc. Alzheimer's Foundation; Department of Veterans Affairs FX This work was supported in part by National Institutes of Health Grants MH0266029, AG027342, and K23-AG028727; Risk Control Strategies Inc. Alzheimer's Foundation; and the Department of Veterans Affairs. These funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, and approval of the manuscript. George Bartzokis, Po H. Lu, and Jim Mintz had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. NR 68 TC 57 Z9 57 U1 0 U2 26 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 2012 VL 72 IS 12 BP 1026 EP 1034 DI 10.1016/j.biopsych.2012.07.010 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 037AS UT WOS:000311074000009 PM 23017471 ER PT J AU Egeland, JA Endicott, J Hostetter, AM Allen, CR Pauls, DL Shaw, JA AF Egeland, Janice A. Endicott, Jean Hostetter, Abram M. Allen, Cleona R. Pauls, David L. Shaw, Jon A. TI A 16-Year Prospective Study of Prodromal Features Prior to BPI Onset in Well Amish Children SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Longitudinal study; Children "at-risk" for BPI; Natural history; Genetic and cultural factors ID OLD-ORDER AMISH; BIPOLAR DISORDER; HIGH-RISK; PARENTS; RELIABILITY; PSYCHOPATHOLOGY; CRITERIA; YOUTH; MANIA AB Background: Longitudinal research of well Amish children over 16 years to identify the pattern and frequency of prodromal symptoms/behaviors associated with onset of BPI disorder during childhood or adolescence. Methods: Parental informants were interviewed annually using structured and semi-structured interviews to record medical, developmental and behavioral/symptomatic data for their children in two samples. The bipolar sample had 115 children with a BPI parent. The control sample had 106 children of well parents, with and without a positive family history for mood disorders. A panel of clinicians assigned risk ratings independently and blind to family relations. Results: Eight children, age 13 or older, onset with BPI in the bipolar sample compared with one in the control sub-sample (well parent of a BPI sibling). The specific "pre-school" behaviors/symptoms that most identified children with BPI from well children in control samples were: sensitivity, crying, hyper-alertness, anxiety/worry and somatic complaints. During school years, parents reported mood (sad) and energy changes (low not high) decreased sleep and fearfulness as key symptoms. Limitations: The sample of 9 BPI onsets is small. However, a variable age of onset means many children remain at risk. Although not statistically significant, 34.6% of the bipolar sample youngsters carry risk ratings compared to 15.2% among controls. Conclusions: The miniclusters of prodromal features that emerged pre-school (ages 1-6), were "episodic" through childhood (7-12) and appeared to mimic adult recurrent illness. Prepubertal onset with mania did not occur. The pattern of prodromal symptoms has clinical relevance for its potential predictive value for onset with BPI disorder and early intervention. (c) 2012 Elsevier B.V. All rights reserved. C1 [Egeland, Janice A.; Hostetter, Abram M.; Allen, Cleona R.; Shaw, Jon A.] Univ Miami, Sch Med, Dept Psychiat & Behav Sci, Miami, FL USA. [Endicott, Jean] Columbia Univ, Coll Phys & Surg, New York, NY 10027 USA. [Endicott, Jean] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Pauls, David L.] Harvard Univ, Sch Med, Boston, MA USA. [Pauls, David L.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat Neurodev Genet Unit, Boston, MA 02114 USA. RP Egeland, JA (reprint author), Univ Miami, Sch Med, Dept Psychiat & Behav Sci, Miami, FL USA. EM ooamish@aol.com FU Eli LILLY Foundation; New York State Department of Mental Health; U.S. National Institute of Mental Health; Cyberonics; Pfizer; Stanley Medical Research Institute; University of Miami Miller School of Medicine; Eli Lilly and Company FX During the past three years, Dr. J.A. Egeland received support from the Eli LILLY Foundation to cover costs for summer field work and CARE workshops. This support presented no conflict of interest nor influenced in any manner the analyses and interpretation of data for this paper.; In the past two years, Dr. J. Endicott has received support from the New York State Department of Mental Health, the U.S. National Institute of Mental Health, Cyberonics and Pfizer. She has served as a consultant or advisory board member to AstraZeneca, Bayer Schering, Cyberonics, Otsuka, Pfizer and Wyeth-Ayerst. None of the above affiliations should result in a conflict of interest related to the subject of the manuscript being submitted.; The CARE (Child and Adolescent Research and Evaluation) program was supported in part by the Stanley Medical Research Institute (1994-2001) with funding from the University of Miami Miller School of Medicine (2001-2005) and Eli Lilly and Company (2006-2011). NR 30 TC 33 Z9 34 U1 6 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD DEC 15 PY 2012 VL 142 IS 1-3 BP 186 EP 192 DI 10.1016/j.jad.2012.04.023 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 030JB UT WOS:000310565900028 PM 22771141 ER PT J AU Farabaugh, A Alpert, J Wisniewski, SR Otto, MW Fava, M Baer, L Perlis, R Friedman, E Nyer, M Bitran, S Balasubramani, GK Inamori, A Trivedi, M Thase, ME AF Farabaugh, Amy Alpert, Jonathan Wisniewski, Stephen R. Otto, Michael W. Fava, Maurizio Baer, Lee Perlis, Roy Friedman, Ed Nyer, Maren Bitran, Stella Balasubramani, G. K. Inamori, Aya Trivedi, Madhukar Thase, Michael E. TI Cognitive therapy for anxious depression in STAR*D: What have we learned? SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Anxious depression; MDD; CT; Psychosocial interventions; STAR*D ID NATIONAL COMORBIDITY SURVEY; MAJOR DEPRESSION; TREATMENT OUTCOMES; ANXIETY DISORDERS; PANIC DISORDER; OUTPATIENTS; FEATURES; IMPACT; METAANALYSIS; FLUOXETINE AB Background: Anxious depression, defined as MDD with high levels of anxiety symptoms, has been associated with lower rates of antidepressant response and remission as well as greater chronicity, suicidality and antidepressant side-effect burden. The primary aim of this study was to assess the effectiveness of cognitive therapy (CT) alone or in combination with medications for anxious versus non-anxious depression. Methods: We assessed the STAR*D study participants who were partial or non-responders to citalopram. Subjects were then either switched (n=696) to a new antidepressant or to CT alone, or they were kept on citalopram and augmented (n=577) with another antidepressant or CT. We compared response and remission rates, across treatment conditions, between those who met criteria for anxious depression and those who did not. Results: Those with anxious depression had significantly lower remission rates based on the QIDS, whether assigned to switch or augmentation, compared to those with non-anxious depression. Those with anxious depression, compared to those without, had significantly lower response rates based on the QIDS only in the switch group. There was no significant interaction between anxious depression and treatment assignment. Limitations: Limitations include the use of citalopram as the only Level 1 pharmacotherapy and medication augmentation option, the relatively small size of the CT arms, use of depression-focused CT rather than anxiety-focused CT, and focus on acute treatment outcomes. Conclusions: Individuals with anxious depression appear to experience higher risk of poorer outcome following pharmacotherapy and/or CT after an initial course of citalopram and continued efforts to target this challenging form of depression are needed. (C) 2012 Elsevier BY. All rights reserved. C1 [Farabaugh, Amy; Alpert, Jonathan; Fava, Maurizio; Baer, Lee; Nyer, Maren; Bitran, Stella; Inamori, Aya] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Wisniewski, Stephen R.; Balasubramani, G. K.] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA 15260 USA. [Otto, Michael W.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Perlis, Roy] Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA. [Friedman, Ed; Thase, Michael E.] Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA 15260 USA. [Thase, Michael E.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Farabaugh, A (reprint author), 1 Bowdoin Square,6th Floor, Boston, MA 02114 USA. EM afarabaugh@partners.org RI Trivedi, Madhukar/A-9029-2013; OI Wisniewski, Stephen/0000-0002-3877-9860; Alpert, Jonathan/0000-0002-4332-908X; Goundappa K, Balasubramani/0000-0001-7221-1825 FU NIMH [N01 MH-90003] FX The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study was supported by the NIMH through the N01 MH-90003 contract. NR 32 TC 15 Z9 15 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD DEC 15 PY 2012 VL 142 IS 1-3 BP 213 EP 218 DI 10.1016/j.jad.2012.04.029 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 030JB UT WOS:000310565900032 PM 22877961 ER PT J AU Rong, PJ Fang, JL Wang, LP Meng, H Liu, J Ma, YG Ben, H Li, L Liu, RP Huang, ZX Zhao, YF Li, X Zhu, B Kong, J AF Rong, Pei-Jing Fang, Ji-Liang Wang, Li-Ping Meng, Hong Liu, Jun Ma, Ying-ge Ben, Hui Li, Liang Liu, Ru-Peng Huang, Zhan-Xia Zhao, Yu-Feng Li, Xia Zhu, Bing Kong, Jian TI Transcutaneous vagus nerve stimulation for the treatment of depression: a study protocol for a double blinded randomized clinical trial SO BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Article DE Major depression disorder; Vagus nerve stimulation; Transcutanecous vagus nerve stimulation ID TREATMENT-RESISTANT DEPRESSION; BLOOD-FLOW; PARTIAL EPILEPSY; PLACEBO; ACUPUNCTURE; PERFORMANCE; MECHANISMS; THERAPY; VNS AB Background: Depressive disorders are the most common form of mental disorders in community and health care settings. Unfortunately, the treatment of Major Depressive Disorder (MDD) is far from satisfactory. Vagus nerve stimulation (VNS) is a relatively new and promising physical treatment for depressive disorders. One particularly appealing element of VNS is the long-term benefit in mood regulation. However, because this intervention involves surgery, perioperative risks, and potentially significant side effects, this treatment has been limited to those patients with treatment-resistant depression who have failed medication trials and exhausted established somatic treatments for major depression, due to intolerance or lack of response. This double-blinded randomized clinical trial aims to overcome these limitations by introducing a novel method of stimulating superficial branches of the vagus nerve on the ear to treat MDD. The rationale is that direct stimulation of the afferent nerve fibers on the ear area with afferent vagus nerve distribution should produce a similar effect as classic VNS in reducing depressive symptoms without the burden of surgical intervention. Design: One hundred twenty cases (60 males) of volunteer patients with mild and moderate depression will be randomly divided into transcutaneous vagus nerve stimulation group (tVNS) and sham tVNS group. The treatment period lasts 4 months and all clinical and physiological measurements are acquired at the beginning and the end of the treatment period. Discussion: This study has the potential to significantly extend the application of VNS treatment for MDD and other disorders (including epilepsy, bipolar disorder, and morbid obesity), resulting in direct benefit to the patients suffering from these highly prevalent disorders. In addition, the results of this double-blinded clinical trial will shed new light on our understanding of acupuncture point specificity, and development of methodologies in clinical trials of acupuncture treatment. C1 [Rong, Pei-Jing; Fang, Ji-Liang; Meng, Hong; Ben, Hui; Li, Liang; Liu, Ru-Peng; Zhu, Bing] China Acad Chinese Med Sci, Inst Acupuncture & Moxibust, Beijing 100700, Peoples R China. [Kong, Jian] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Fang, Ji-Liang; Liu, Jun] China Acad Chinese Med Sci, Guang An Men Hosp, Beijing 100053, Peoples R China. [Wang, Li-Ping] Beijing Univ TCM, Huguosi TCM Hosp, Beijing, Peoples R China. [Ma, Ying-ge; Huang, Zhan-Xia; Li, Xia] Beijing Univ Chinese Med, Beijing 100029, Peoples R China. [Zhao, Yu-Feng] China Acad Chinese Med Sci, Clin Evaluat Ctr, Beijing 100700, Peoples R China. RP Rong, PJ (reprint author), China Acad Chinese Med Sci, Inst Acupuncture & Moxibust, Beijing 100700, Peoples R China. EM rongpj@hotmail.com; zhubing@mail.cintcm.ac.cn FU National twelfth five-year science and technology support program [2012BAF14B10]; Natural Science Foundation of Beijing China [711117] FX This scientific work was supported byNational twelfth five-year science and technology support program (2012BAF14B10) and a Natural Science Foundation of Beijing China (No. 711117) Grant to PJ. Rong. We thank for, Rupeng Liu who providing the consent for his ear on the publication. NR 26 TC 19 Z9 19 U1 2 U2 27 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6882 J9 BMC COMPLEM ALTERN M JI BMC Complement. Altern. Med. PD DEC 14 PY 2012 VL 12 AR 255 DI 10.1186/1472-6882-12-255 PG 6 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 067EM UT WOS:000313276800001 PM 23241431 ER PT J AU Sebastian, C Satterstrom, FK Haigis, MC Mostoslavsky, R AF Sebastian, Carlos Satterstrom, F. Kyle Haigis, Marcia C. Mostoslavsky, Raul TI From Sirtuin Biology to Human Diseases: An Update SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID FATTY-ACID OXIDATION; MITOCHONDRIAL PROTEIN HYPERACETYLATION; HISTONE DEACETYLASE SIRT6; DEPENDENT GENE-EXPRESSION; INDUCIBLE FACTOR 1-ALPHA; LIFE-SPAN; CALORIE RESTRICTION; SACCHAROMYCES-CEREVISIAE; CELL-DIFFERENTIATION; CARDIAC-HYPERTROPHY AB Originally rising to notoriety for their role in the regulation of aging, sirtuins are a family of NAD(+)-dependent enzymes that have been connected to a steadily growing set of biological processes. In addition to regulating aging, sirtuins play key roles in the maintenance of organismal metabolic homeostasis. These enzymes also have primarily protective functions in the development of many age-related diseases, including cancer, neurodegeneration, and cardiovascular disease. In this minireview, we provide an update on the known roles for each of the seven mammalian sirtuins in these areas. C1 [Satterstrom, F. Kyle; Haigis, Marcia C.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Sebastian, Carlos; Mostoslavsky, Raul] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. [Satterstrom, F. Kyle] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. RP Haigis, MC (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM marcia_haigis@hms.harvard.edu; rmostoslavsky@mgh.harvard.edu FU National Institutes of Health [AG032375, DK088190, GM093072, T32 DK007260]; Beatriu de Pinos postdoctoral fellowship; Paul F. Glenn Foundation for Medical Research FX This work was supported, in whole or in part, by National Institutes of Health Grant AG032375 (to M. C. H.), Grants DK088190 and GM093072 (to R. M.), and Training Grant T32 DK007260 (to F. K. S.). This is the fourth article in the Thematic Minireview Series on Sirtuins: From Biochemistry to Health and Disease.; Recipient of a Beatriu de Pinos postdoctoral fellowship.; Supported by the Paul F. Glenn Foundation for Medical Research. To whom correspondence may be addressed. E-mail: marcia_haigis@hms.harvard.edu. NR 105 TC 73 Z9 76 U1 0 U2 33 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 14 PY 2012 VL 287 IS 51 BP 42444 EP 42452 DI 10.1074/jbc.R112.402768 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 056OX UT WOS:000312501600005 PM 23086954 ER PT J AU Rauen, T Grammatikos, AP Hedrich, CM Floege, J Tenbrock, K Ohl, K Kyttaris, VC Tsokos, GC AF Rauen, Thomas Grammatikos, Alexandros P. Hedrich, Christian M. Floege, Juergen Tenbrock, Klaus Ohl, Kim Kyttaris, Vasileios C. Tsokos, George C. TI cAMP-responsive Element Modulator alpha (CREM alpha) Contributes to Decreased Notch-1 Expression in T Cells from Patients with Active Systemic Lupus Erythematosus (SLE) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNALING PATHWAY; IL-2 PRODUCTION; AUTOIMMUNE; DISEASE; GENE; METHYLATION; LYMPHOCYTES; BINDING; DIFFERENTIATION; MECHANISMS AB Notch signaling constitutes an evolutionarily conserved pathway that transduces signals between neighboring cells and determines major decisions in cell proliferation, survival, and differentiation. Notch signaling has been shown to play a pivotal role during T cell lineage determination. T lymphocytes from patients with systemic lupus erythematosus (SLE) display a severely altered phenotype with several molecular and functional aberrations, including defective capacities to up-regulate Notch-1 receptor expression upon T cell receptor activation. Here, we demonstrate that basal Notch-1 expression is decreased in T cells from active SLE patients at the mRNA and protein levels in various T cell subpopulations. Notch-1 transcript numbers inversely correlate with disease activity in SLE patients. We provide evidence that both enhanced histone H3 methylation and CpG DNA methylation of the human Notch-1 promoter contribute to decreased Notch-1 expression in SLE T cells. Previous data from our group identified cAMP-responsive element modulator alpha (CREM alpha), which is up-regulated in SLE T cells, as a key regulator of epigenetic patterns and gene transcription, e. g. that of IL2 and IL17 genes. In this study, we observed increased CREM alpha binding to the Notch-1 promoter, which eventually resulted in significantly reduced Notch-1 promoter activity and gene transcription. Notably, decreased Notch-1 levels were associated with elevated IL-17A levels. Our data suggest a role for Notch-1 in SLE immunopathogenesis, and for the first time, we present molecular mechanisms that mediate dysregulated Notch-1 expression in SLE T cells. C1 [Rauen, Thomas; Grammatikos, Alexandros P.; Hedrich, Christian M.; Kyttaris, Vasileios C.; Tsokos, George C.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Rheumatol,Dept Med, Boston, MA 02115 USA. [Rauen, Thomas; Floege, Juergen] Rhein Westfal TH Aachen, Dept Nephrol & Clin Immunol, D-52074 Aachen, Germany. [Tenbrock, Klaus; Ohl, Kim] Rhein Westfal TH Aachen, Dept Pediat, Div Allergol & Immunol, D-52074 Aachen, Germany. RP Tsokos, GC (reprint author), Beth Israel Deaconess Med Ctr CLS 937, Div Rheumatol, Dept Med, 330 Brookline Ave, Boston, MA 02115 USA. EM gtsokos@bidmc.harvard.edu FU National Institutes of Health [R01 AI42269, R01 AI49954, R01 AI85567]; Deutsche Forschungsgemeinschaft [RA1927-1/1]; START Grant for Young Researchers of the Medical Faculty of RWTH University of Aachen; Interdisziplinares Zentrum fur Klinische Forschung (IZKF) Aachen [E6-6] FX This work was supported, in whole or in part, by National Institutes of Health Grants R01 AI42269, R01 AI49954, and R01 AI85567 (to G. C. T.). This work was also supported by Deutsche Forschungsgemeinschaft Grant RA1927-1/1 and a START Grant for Young Researchers of the Medical Faculty of RWTH University of Aachen (to T. R.) and Interdisziplinares Zentrum fur Klinische Forschung (IZKF) Aachen Grant E6-6 (to K. T.). NR 40 TC 14 Z9 15 U1 1 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 14 PY 2012 VL 287 IS 51 BP 42525 EP 42532 DI 10.1074/jbc.M112.425371 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 056OX UT WOS:000312501600014 PM 23124208 ER PT J AU Gibbs, VC AF Gibbs, Verna C. TI Thinking in three's: Changing surgical patient safety practices in the complex modern operating room SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Complex adaptive systems; Wrong site surgery; Retained surgical items; Retained foreign objects; Retained foreign bodies; Surgical patient safety; Surgical fires; Safety checklist ID NEVER EVENTS; SITE SURGERY; HEALTH-CARE; PREVENTION; MANAGEMENT; FIRES AB The three surgical patient safety events, wrong site surgery, retained surgical items (RSI) and surgical fires are rare occurrences and thus their effects on the complex modern operating room (OR) are difficult to study. The likelihood of occurrence and the magnitude of risk for each of these surgical safety events are undefined. Many providers may never have a personal experience with one of these events and training and education on these topics are sparse. These circumstances lead to faulty thinking that a provider won't ever have an event or if one does occur the provider will intuitively know what to do. Surgeons are not preoccupied with failure and tend to usually consider good outcomes, which leads them to ignore or diminish the importance of implementing and following simple safety practices. These circumstances contribute to the persistent low level occurrence of these three events and to the difficulty in generating sufficient interest to resource solutions. Individual facilities rarely have the time or talent to understand these events and develop lasting solutions. More often than not, even the most well meaning internal review results in a new line to a policy and some rigorous enforcement mandate. This approach routinely fails and is another reason why these problems are so persistent. Vigilance actions alone have been unsuccessful so hospitals now have to take a systematic approach to implementing safer processes and providing the resources for surgeons and other stakeholders to optimize the OR environment. This article discusses standardized processes of care for mitigation of injury or outright prevention of wrong site surgery, RSI and surgical fires in an action-oriented framework illustrating the strategic elements important in each event and focusing on the responsibilities for each of the three major OR agents-anesthesiologists, surgeons and nurses. A Surgical Patient Safety Checklist Is discussed that incorporates the necessary elements to bring these team members together and influence the emergence of a safer OR. (C) 2012 Baishideng. All rights reserved. C1 San Francisco VA Med Ctr, Dept Surg, San Francisco, CA 94121 USA. RP Gibbs, VC (reprint author), San Francisco VA Med Ctr, Dept Surg, SFVAMC 112,4150 Clement Str, San Francisco, CA 94121 USA. EM verna.gibbs@va.gov NR 28 TC 6 Z9 6 U1 0 U2 18 PU BAISHIDENG PUBL GRP CO LTD PI WANCHAI PA ROOM 1701, 17-F, HENAN BUILDING, NO. 90, JAFFE RD, WANCHAI, HONG KONG 100025, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD DEC 14 PY 2012 VL 18 IS 46 BP 6712 EP 6719 DI 10.3748/wjg.v18.i46.6712 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 063AE UT WOS:000312966000004 PM 23239908 ER PT J AU Schuster, M Glauben, R Plaza-Sirvent, C Schreiber, L Annemann, M Floess, S Kuhl, AA Clayton, LK Sparwasser, T Schulze-Osthoff, K Pfeffer, K Huehn, J Siegmund, B Schmitz, I AF Schuster, Marc Glauben, Rainer Plaza-Sirvent, Carlos Schreiber, Lisa Annemann, Michaela Floess, Stefan Kuehl, Anja A. Clayton, Linda K. Sparwasser, Tim Schulze-Osthoff, Klaus Pfeffer, Klaus Huehn, Jochen Siegmund, Britta Schmitz, Ingo TI I kappa B-NS Protein Mediates Regulatory T Cell Development via Induction of the Foxp3 Transcription Factor SO IMMUNITY LA English DT Article ID C-REL; THYMIC DEVELOPMENT; EXPRESSION; GENE; ACTIVATION; RECEPTOR; CARMA1; SELF; INFLAMMATION; DISRUPTION AB Forkhead box P3 positive (Foxp3(+)) regulatory T (Treg) cells suppress immune responses and regulate peripheral tolerance. Here we show that the atypical inhibitor of NF kappa B (I kappa B) I kappa B-NS drives Foxp3 expression via association with the promoter and the conserved noncoding sequence 3 (CNS3) of the Foxp3 locus. Consequently, I kappa B-NS deficiency leads to a substantial reduction of Foxp3+ Treg cells in vivo and impaired Foxp3 induction upon transforming growth factor-beta (TGF-13) treatment in vitro. Moreover, fewer Foxp3+ Treg cells developed from I kappa B-NS-deficient CD25(-)CD4(+) T cells adoptively transferred into immunodeficient recipients. Importantly, I kappa B-NS was required for the transition of immature GITR(+)CD25(+) Foxp3(-) thymic Treg cell precursors into Foxp3(+) cells. In contrast to mice lacking c-Rel or Carmal, I kappa B-NS-deficient mice do not show reduced Treg precursor cells. Our results demonstrate that IkBNs critically regulates Treg cell development in the thymus and during gut inflammation, indicating that strategies targeting IkBNs could modulate the Treg cell compartment. C1 [Schreiber, Lisa; Floess, Stefan; Huehn, Jochen; Schmitz, Ingo] Helmholtz Ctr Infect Res, Det Expt Immunol, D-38124 Braunschweig, Germany. [Schuster, Marc; Plaza-Sirvent, Carlos; Annemann, Michaela; Schmitz, Ingo] Univ Magdeburg, Inst Mol & Clin Immunol, D-39120 Magdeburg, Germany. [Kuehl, Anja A.] Charite, Inst Pathol, D-12203 Berlin, Germany. [Glauben, Rainer; Siegmund, Britta] Charite, Med Klin 1, D-12203 Berlin, Germany. [Clayton, Linda K.] Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02215 USA. [Clayton, Linda K.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Sparwasser, Tim] TWINCORE, Inst Infect Immunol, D-30625 Hannover, Germany. [Schulze-Osthoff, Klaus] Univ Tubingen, Interfac Inst Biochem, D-72076 Tubingen, Germany. [Pfeffer, Klaus] Univ Dusseldorf, Inst Med Microbiol, D-40225 Dusseldorf, Germany. [Pfeffer, Klaus] Univ Dusseldorf, Hosp Hyg, D-40225 Dusseldorf, Germany. RP Schmitz, I (reprint author), Helmholtz Ctr Infect Res, Det Expt Immunol, D-38124 Braunschweig, Germany. EM ingo.schmitz@helmholtz-hzi.de RI Schmitz, Ingo/G-2093-2013; Schulze-Osthoff, Klaus/N-9025-2013 OI Schmitz, Ingo/0000-0002-5360-0419; Schulze-Osthoff, Klaus/0000-0003-1443-2720 FU Deutsche Forschungsgemeinschaft [SI 749/5-3]; SFB [738/C-6, 685/B-7] FX We thank Sabrina Schumann, Dominique Gollasch, Stephanie Grosch, and Inka Freise for their excellent technical assistance, Ralf Hocker for help with apoptosis experiments, and Alisha Walker for critically reading the manuscript. We are grateful to David Dettbarn and colleagues for excellent mouse husbandry. Rag1-/- mice were a kind gift from Thomas Blankenstein and Charite Berlin. DNA methylation experiments were developed and performed by Udo Baron and Sven Olek at Epiontis GmbH. We thank the Forschungs-kommission of the Heinrich-Heine University Dusseldorf for initial funding. Further support was provided by the Deutsche Forschungsgemeinschaft (SI 749/5-3) and the SFB 738/C-6 and SFB 685/B-7. NR 42 TC 25 Z9 25 U1 0 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC 14 PY 2012 VL 37 IS 6 BP 998 EP 1008 DI 10.1016/j.immuni.2012.08.023 PG 11 WC Immunology SC Immunology GA 057PH UT WOS:000312575000009 PM 23200824 ER PT J AU Sakai, J Li, JY Subramanian, KK Mondal, S Bajrami, B Hattori, H Jia, YH Dickinson, BC Zhong, J Ye, KQ Chang, CJ Ho, YS Zhou, J Luo, HBR AF Sakai, Jiro Li, Jingyu Subramanian, Kulandayan K. Mondal, Subhanjan Bajrami, Besnik Hattori, Hidenori Jia, Yonghui Dickinson, Bryan C. Zhong, Jia Ye, Keqiang Chang, Christopher J. Ho, Ye-Shih Zhou, Jun Luo, Hongbo R. TI Reactive Oxygen Species-Induced Actin Glutathionylation Controls Actin Dynamics in Neutrophils SO IMMUNITY LA English DT Article ID BETA-ACTIN; S-GLUTATHIONYLATION; SIGNAL-TRANSDUCTION; LUNG INFLAMMATION; HYDROGEN-PEROXIDE; REDOX; GLUTAREDOXIN; PROTEINS; MOLECULE; STRESS AB The regulation of actin dynamics is pivotal for cellular processes such as cell adhesion, migration, and phagocytosis and thus is crucial for neutrophils to fulfill their roles in innate immunity. Many factors have been implicated in signal-induced actin polymerization, but the essential nature of the potential negative modulators are still poorly understood. Here we report that NADPH oxidase-dependent physiologically generated reactive oxygen species (ROS) negatively regulate actin polymerization in stimulated neutrophils via driving reversible actin glutathionylation. Disruption of glutaredoxin 1 (Grx1), an enzyme that catalyzes actin deglutathionylation, increased actin glutathionylation, attenuated actin polymerization, and consequently impaired neutrophil polarization, chemotaxis, adhesion, and phagocytosis. Consistently, Grx1-deficient murine neutrophils showed impaired in vivo recruitment to sites of inflammation and reduced bactericidal capability. Together, these results present a physiological role for glutaredoxin and ROS- induced reversible actin glutathionylation in regulation of actin dynamics in neutrophils. C1 [Sakai, Jiro; Li, Jingyu; Subramanian, Kulandayan K.; Mondal, Subhanjan; Bajrami, Besnik; Hattori, Hidenori; Jia, Yonghui; Zhong, Jia; Luo, Hongbo R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Sakai, Jiro; Li, Jingyu; Subramanian, Kulandayan K.; Mondal, Subhanjan; Bajrami, Besnik; Hattori, Hidenori; Jia, Yonghui; Zhong, Jia; Luo, Hongbo R.] Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. [Sakai, Jiro; Li, Jingyu; Subramanian, Kulandayan K.; Mondal, Subhanjan; Bajrami, Besnik; Hattori, Hidenori; Jia, Yonghui; Zhong, Jia; Luo, Hongbo R.] Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA. [Li, Jingyu; Zhou, Jun] Nankai Univ, Tianjin Key Lab Prot Sci, Dept Genet & Cell Biol, Coll Life Sci, Tianjin 300071, Peoples R China. [Dickinson, Bryan C.; Chang, Christopher J.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA. [Dickinson, Bryan C.; Chang, Christopher J.] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA. [Ye, Keqiang] Emory Univ, Dept Pathol & Lab Med, Sch Med, Atlanta, GA 30307 USA. [Ho, Ye-Shih] Wayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48202 USA. [Ho, Ye-Shih] Wayne State Univ, Dept Biochem & Mol Biol, Detroit, MI 48202 USA. RP Luo, HBR (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM hongbo.luo@childrens.harvard.edu RI Zhou, Jun/D-4654-2017; OI Zhou, Jun/0000-0001-7858-8260; Sakai, Jiro/0000-0002-2526-2766 FU NIH [HL085100, GM076084, GM 79465] FX The authors thank L. Silberstein, J. Manis, and L. Chai for helpful discussions and Y. Janssen-Heininger (The University of Vermont) for preparing and sending Grx1-/- mice. H.R.L. is supported by NIH grants HL085100 and GM076084. C.J.C. is supported by NIH GM 79465 and is an investigator with the Howard Hughes Medical Institute. J.S., J.L., and K.K.S. designed and carried out experiments, analyzed data, and prepared the manuscript. B.B., S.M., H.H., Y.J., KY., and J.Z. helped with designing experiments, analyzing data, and evaluating the manuscript. J.Z. bred mice. B.C.D. and C.J.C. synthesized and provided PF6-AM and Y.-S.H. provided Grx1-/- mice. H.R.L. designed experiments, analyzed data, and wrote the paper. NR 33 TC 56 Z9 57 U1 4 U2 21 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC 14 PY 2012 VL 37 IS 6 BP 1037 EP 1049 DI 10.1016/j.immuni.2012.08.017 PG 13 WC Immunology SC Immunology GA 057PH UT WOS:000312575000012 PM 23159440 ER PT J AU Groom, JR Richmond, J Murooka, TT Sorensen, EW Sung, JH Bankert, K von Andrian, UH Moon, JJ Mempel, TR Luster, AD AF Groom, Joanna R. Richmond, Jillian Murooka, Thomas T. Sorensen, Elizabeth W. Sung, Jung Hwan Bankert, Katherine von Andrian, Ulrich H. Moon, James J. Mempel, Thorsten R. Luster, Andrew D. TI CXCR3 Chemokine Receptor-Ligand Interactions in the Lymph Node Optimize CD4(+) T Helper 1 Cell Differentiation SO IMMUNITY LA English DT Article ID T-CELLS; DENDRITIC CELLS; IFN-GAMMA; CLASS-II; IN-VIVO; EXPRESSION; EFFECTOR; INFECTION; LYMPHOCYTES; ANTIGEN AB Differentiation of naive CD4(+) T cells into T helper (Th) cells is a defining event in adaptive immunity. The cytokines and transcription factors that control Th cell differentiation are understood, but it is not known how this process is orchestrated within lymph nodes (LNs). Here we have shown that the CXCR3 chemokine receptor was required for optimal generation of interferon-gamma (IFN-gamma)-secreting Th1 cells in vivo. By using a CXCR3 ligand reporter mouse, we found that stromal cells predominately expressed the chemokine ligand CXCL9 whereas hematopoietic cells expressed CXCL10 in LNs. Dendritic cell (DC)derived CXCL10 facilitated T cell-DC interactions in LNs during T cell priming while both chemokines guided intranodal positioning of CD4(+) T cells to interfollicular and medullary zones. Thus, different chemokines acting on the same receptor can function locally to facilitate DC-T cell interactions and globally to influence intranodal positioning, and both functions contribute to Th1 cell differentiation. C1 [Groom, Joanna R.; Richmond, Jillian; Murooka, Thomas T.; Sorensen, Elizabeth W.; Bankert, Katherine; Moon, James J.; Mempel, Thorsten R.; Luster, Andrew D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA 02114 USA. [Sung, Jung Hwan; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Sung, Jung Hwan; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA. RP Luster, AD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA 02114 USA. EM aluster@mgh.harvard.edu RI von Andrian, Ulrich/A-5775-2008 FU NIH [CA069212, A1078897]; NHMRC, Australia [516791]; Samsung Scholarship FX Work was supported by the NIH grants CA069212 (to A.D.L.) and A1078897 (to U.H.v.A.). J.R.G. was supported by the NH&MRC, Australia (Fellowship 516791). J.H.S. was supported by a Samsung Scholarship. We thank D. Alvarez for assistance with LCMV infections, J. Farber for the Cxcl9-/- breeding breeding pair, and C. Gerard for the Cxcr3-/- breeding pair. NR 35 TC 97 Z9 99 U1 0 U2 16 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC 14 PY 2012 VL 37 IS 6 BP 1091 EP 1103 DI 10.1016/j.immuni.2012.08.016 PG 13 WC Immunology SC Immunology GA 057PH UT WOS:000312575000016 PM 23123063 ER PT J AU Xu, Y Ayrapetov, MK Xu, C Gursoy-Yuzugullu, O Hu, YD Price, BD AF Xu, Ye Ayrapetov, Marina K. Xu, Chang Gursoy-Yuzugullu, Ozge Hu, Yiduo Price, Brendan D. TI Histone H2A.Z Controls a Critical Chromatin Remodeling Step Required for DNA Double-Strand Break Repair SO MOLECULAR CELL LA English DT Article ID SACCHAROMYCES-CEREVISIAE; NUCLEOSOME STABILITY; GENOME INTEGRITY; DAMAGE RESPONSE; ACETYLATION; VARIANT; GENE; RESECTION; PROTEINS; TIP60 AB Chromatin remodeling during DNA double-strand break (DSB) repair is required to facilitate access to and repair of DSBs. This remodeling requires increased acetylation of histones and a shift in nucleosome organization to create open, relaxed chromatin domains. However, the underlying mechanism driving changes in nucleosome structure at DSBs is poorly defined. Here, we demonstrate that histone H2A.Z is exchanged onto nucleosomes at DSBs by the p400 remodeling ATPase. H2A.Z exchange at DSBs shifts the chromatin to an open conformation and is required for acetylation and ubiquitination of histones and for loading of the brca1 complex. H2A.Z exchange also restricts single-stranded DNA production by nucleases and is required for loading of the Ku70/Ku80 DSB repair protein. H2A.Z exchange therefore promotes specific patterns of histone modification and reorganization of the chromatin architecture, leading to the assembly of a chromatin template that is an efficient substrate for the DSB repair machinery. C1 [Xu, Ye; Ayrapetov, Marina K.; Xu, Chang; Gursoy-Yuzugullu, Ozge; Price, Brendan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Genome Stabil & DNA Repair,Dept Radiat Oncol, Boston, MA 02215 USA. [Hu, Yiduo; Price, Brendan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. RP Price, BD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Genome Stabil & DNA Repair,Dept Radiat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM brendan_price@dfci.harvard.edu FU NCI [CA64585, CA93602]; DOD Breast Cancer Program FX We thank J. Stark for altNHEJ cells, F. Urnov and J.-S. Kim for ZFNs. R. Baer for CtIP antibody, and J. Gaudreau for shRNA vectors to H2A.Z. We thank Haico Van Attikum for helpful discussions. This work was supported by grants from NCI (CA64585 and CA93602) and the DOD Breast Cancer Program to B.D.P. B.D.P. and Y.X. conceived the research, wrote the paper, and carried out data analysis. Y.X. carried out the majority of the experiments, participated in data analysis, and planned experiments. M.K.A. and Y.H. carried out laser-striping experiments and contributed to data analysis. C.X. and O.G.-Y. carried out some of the ChIP experiments and contributed to protocol development. All authors discussed the results and commented on the manuscript. NR 54 TC 85 Z9 90 U1 1 U2 28 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD DEC 14 PY 2012 VL 48 IS 5 BP 723 EP 733 DI 10.1016/j.molcel.2012.09.026 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 055RH UT WOS:000312433900008 PM 23122415 ER PT J AU Lee, JT AF Lee, Jeannie T. TI Epigenetic Regulation by Long Noncoding RNAs SO SCIENCE LA English DT Review ID X-CHROMOSOME INACTIVATION; NATURAL ANTISENSE TRANSCRIPTS; XIST RNA; CHROMATIN-STRUCTURE; GENE-EXPRESSION; MALE DROSOPHILA; CODING GENE; HUMAN-CELLS; PLURIPOTENCY; STABILITY AB Recent studies show that transcription of the mammalian genome is not only pervasive but also enormously complex. It is estimated that an average of 10 transcription units, the vast majority of which make long noncoding RNAs (lncRNAs), may overlap each traditional coding gene. These lncRNAs include not only antisense, intronic, and intergenic transcripts but also pseudogenes and retrotransposons. Do they universally have function, or are they merely transcriptional by-products of conventional coding genes? A glimpse into the molecular biology of multiple emerging lncRNA systems reveals the "Wild West" landscape of their functions and mechanisms and the key problems to solve in the years ahead toward understanding these intriguing macromolecules. C1 [Lee, Jeannie T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst HHMI,Dept Mol Biol, Boston, MA 02138 USA. [Lee, Jeannie T.] Harvard Univ, Dept Genet, Sch Med, Boston, MA 02138 USA. RP Lee, JT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst HHMI,Dept Mol Biol, Boston, MA 02138 USA. EM lee@molbio.mgh.harvard.edu FU Howard Hughes Medical Institute; NIGMS NIH HHS [R01 GM058839, R37 GM058839] NR 79 TC 371 Z9 401 U1 48 U2 404 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD DEC 14 PY 2012 VL 338 IS 6113 BP 1435 EP 1439 DI 10.1126/science.1231776 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 053DN UT WOS:000312250800039 PM 23239728 ER PT J AU Xu, KX Wu, ZJ Groner, AC He, HSHS Cai, CM Lis, RT Wu, XQ Stack, EC Loda, M Liu, T Xu, H Cato, L Thornton, JE Gregory, RI Morrissey, C Vessella, RL Montironi, R Magi-Galluzzi, C Kantoff, PW Balk, SP Liu, XS Brown, M AF Xu, Kexin Wu, Zhenhua Jeremy Groner, Anna C. He, Housheng Hansen Cai, Changmeng Lis, Rosina T. Wu, Xiaoqiu Stack, Edward C. Loda, Massimo Liu, Tao Xu, Han Cato, Laura Thornton, James E. Gregory, Richard I. Morrissey, Colm Vessella, Robert L. Montironi, Rodolfo Magi-Galluzzi, Cristina Kantoff, Philip W. Balk, Steven P. Liu, X. Shirley Brown, Myles TI EZH2 Oncogenic Activity in Castration-Resistant Prostate Cancer Cells Is Polycomb-Independent SO SCIENCE LA English DT Article ID GENE-EXPRESSION; HISTONE METHYLTRANSFERASE; SUPPRESSES METHYLATION; PHOSPHORYLATION; PROGRESSION; LYSINE-27; PROTEIN; H3; COMPLEX; AKT AB Epigenetic regulators represent a promising new class of therapeutic targets for cancer. Enhancer of zeste homolog 2 (EZH2), a subunit of Polycomb repressive complex 2 (PRC2), silences gene expression via its histone methyltransferase activity. We found that the oncogenic function of EZH2 in cells of castration-resistant prostate cancer is independent of its role as a transcriptional repressor. Instead, it involves the ability of EZH2 to act as a coactivator for critical transcription factors including the androgen receptor. This functional switch is dependent on phosphorylation of EZH2 and requires an intact methyltransferase domain. Hence, targeting the non-PRC2 function of EZH2 may have therapeutic efficacy for treating metastatic, hormone-refractory prostate cancer. C1 [Xu, Kexin; Wu, Zhenhua Jeremy; Groner, Anna C.; He, Housheng Hansen; Liu, Tao; Xu, Han; Cato, Laura; Liu, X. Shirley; Brown, Myles] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. [Xu, Kexin; Groner, Anna C.; He, Housheng Hansen; Lis, Rosina T.; Wu, Xiaoqiu; Stack, Edward C.; Loda, Massimo; Cato, Laura; Kantoff, Philip W.; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Xu, Kexin; Groner, Anna C.; He, Housheng Hansen; Cai, Changmeng; Lis, Rosina T.; Wu, Xiaoqiu; Stack, Edward C.; Loda, Massimo; Cato, Laura; Kantoff, Philip W.; Balk, Steven P.; Brown, Myles] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Wu, Zhenhua Jeremy; He, Housheng Hansen; Liu, Tao; Xu, Han; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Wu, Zhenhua Jeremy; He, Housheng Hansen; Liu, Tao; Xu, Han; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Cai, Changmeng; Balk, Steven P.] Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Boston, MA 02215 USA. [Lis, Rosina T.; Wu, Xiaoqiu; Stack, Edward C.; Loda, Massimo] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Lis, Rosina T.; Stack, Edward C.; Loda, Massimo] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Loda, Massimo] Kings Coll London, Div Canc Studies, London SE1 8UB, England. [Thornton, James E.; Gregory, Richard I.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Thornton, James E.; Gregory, Richard I.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Morrissey, Colm; Vessella, Robert L.] Univ Washington, Med Ctr, Dept Urol, Seattle, WA 98195 USA. [Vessella, Robert L.] Puget Sound VA Hlth Care Syst, Seattle, WA 98108 USA. [Montironi, Rodolfo] Polytech Univ Marche Reg, United Hosp, Sect Pathol Anat, I-60126 Ancona, Italy. [Magi-Galluzzi, Cristina] Cleveland Clin, Pathol & Lab Med Inst, Glickman Urol & Kidney Inst, Dept Canc Biol,Taussig Canc Inst, Cleveland, OH 44195 USA. RP Liu, XS (reprint author), Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. EM xsliu@jimmy.harvard.edu; myles_brown@dfci.harvard.edu RI Liu, Tao/G-3585-2010; OI Liu, Tao/0000-0002-8818-8313; Brown, Myles/0000-0002-8213-1658; Liu, Tao/0000-0003-0446-9001; Cai, Changmeng/0000-0002-8701-2586 FU Prostate Cancer Foundation (PCF); Swiss National Science Foundation; NSF; A. David Mazzone Project Development Award; PCF Challenge Awards; U.S. Department of Defense Idea Development Award [PC100950]; National Cancer Institute [CA131945, CA89021, CA90381]; NIH [CA166507, CA111803, CA090381, GM99409, CA85859, CA097186] FX We thank H. Huang, A. Chinnaiyan, Y. Shang, and D. Reinberg for sharing their reagents, and Y. Qiu, X. Yang, J. Xu, and M. Ni for technical support and advice. Supported by a Prostate Cancer Foundation (PCF) Young Investigator Award (K. X.); a Swiss National Science Foundation prospective researcher fellowship (A. C. G.); a NSF graduate research fellowship (J. E. T.); an A. David Mazzone Project Development Award (M. B.); PCF Challenge Awards (S. P. B. and M. B.); U.S. Department of Defense Idea Development Award PC100950 (S. P. B.); National Cancer Institute grants CA131945, CA89021, and CA90381 (M. L.); and NIH grants CA166507 (C. C.), CA111803 (S. P. B.), CA090381 (M. B., S. P. B., P. W. K.), GM99409 (X. S. L.), and CA85859 and CA097186 (C. M., R. L. V.). All data sets have been deposited in the Gene Expression Omnibus database (GSE39461). M. B. serves as a consultant to Novartis Pharmaceuticals. NR 22 TC 222 Z9 232 U1 2 U2 53 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD DEC 14 PY 2012 VL 338 IS 6113 BP 1465 EP 1469 DI 10.1126/science.1227604 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 053DN UT WOS:000312250800047 PM 23239736 ER PT J AU Birmann, BM Neuhouser, ML Rosner, B Albanes, D Buring, JE Giles, GG Lan, Q Lee, IM Purdue, MP Rothman, N Severi, G Yuan, JM Anderson, KC Pollak, M Rifai, N Hartge, P Landgren, O Lessin, L Virtamo, J Wallace, RB Manson, JE Colditz, GA AF Birmann, Brenda M. Neuhouser, Marian L. Rosner, Bernard Albanes, Demetrius Buring, Julie E. Giles, Graham G. Lan, Qing Lee, I-Min Purdue, Mark P. Rothman, Nathaniel Severi, Gianluca Yuan, Jian-Min Anderson, Kenneth C. Pollak, Michael Rifai, Nader Hartge, Patricia Landgren, Ola Lessin, Lawrence Virtamo, Jarmo Wallace, Robert B. Manson, Joann E. Colditz, Graham A. TI Prediagnosis biomarkers of insulin-like growth factor-1, insulin, and interleukin-6 dysregulation and multiple myeloma risk in the Multiple Myeloma Cohort Consortium SO BLOOD LA English DT Article ID UNDETERMINED SIGNIFICANCE MGUS; SINGAPORE CHINESE HEALTH; BODY-MASS INDEX; MONOCLONAL GAMMOPATHY; CANCER-RISK; WOMENS HEALTH; BREAST-CANCER; CELL-GROWTH; DISEASE; MEN AB Insulin-like growth factor-1 (IGF-1), insulin, and IL-6 are dysregulated in multiple myeloma pathogenesis and may also contribute to multiple myeloma etiology. To examine their etiologic role, we prospectively analyzed concentrations of serologic markers in 493 multiple myeloma cases and 978 controls from 8 cohorts in the Multiple Myeloma Cohort Consortium. We computed odds ratios (ORs) and 95% confidence intervals (CIs) for multiple myeloma per 1-SD increase in biomarker concentration using conditional logistic regression. We examined heterogeneity by time since blood collection (<= 3, 4- <= 6, and > 6 years) in stratified models. Fasting IGF binding protein-1 concentration was associated with multiple myeloma risk within 3 years (OR, 95% CI per 1-SD increase: 2.3, 1.4-3.8, P = .001) and soluble IL-6 receptor level was associated within 6 years after blood draw (OR (<= 3 years), 95% CI, 1.4, 1.1-1.9, P = .01; OR4- (<= 6 years), 95% CI, 1.4, 1.1-1.7, P = .002). No biomarker was associated with longer-term multiple myeloma risk (ie, > 6 years). Interactions with time were statistically significant (IGF binding protein-1, P-heterogeneity = .0016; sIL6R, P-heterogeneity = .016). The time-restricted associations probably reflect the bioactivity of tumor and microenvironment cells in transformation from monoclonal gammopathy of undetermined significance or smoldering multiple myeloma to clinically manifest multiple myeloma. (Blood. 2012; 120(25): 4929-4937) C1 [Birmann, Brenda M.; Rosner, Bernard] Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA 02115 USA. [Birmann, Brenda M.; Rosner, Bernard; Buring, Julie E.; Lee, I-Min; Rifai, Nader; Manson, Joann E.] Harvard Univ, Sch Med, Boston, MA USA. [Neuhouser, Marian L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Neuhouser, Marian L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Neuhouser, Marian L.] Univ Washington, Grad Program Nutr Sci, Seattle, WA 98195 USA. [Albanes, Demetrius; Lan, Qing; Purdue, Mark P.; Rothman, Nathaniel; Hartge, Patricia; Landgren, Ola] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Buring, Julie E.; Lee, I-Min; Manson, Joann E.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Buring, Julie E.; Lee, I-Min; Manson, Joann E.; Colditz, Graham A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giles, Graham G.; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Australia. [Giles, Graham G.; Severi, Gianluca] Univ Melbourne, Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Parkville, Vic 3052, Australia. [Giles, Graham G.] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia. [Yuan, Jian-Min] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [Yuan, Jian-Min] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Yuan, Jian-Min] Univ Pittsburgh, Inst Canc, Div Canc Control & Populat Sci, Pittsburgh, PA USA. [Yuan, Jian-Min] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Anderson, Kenneth C.] Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Pollak, Michael] McGill Univ, Jewish Gen Hosp, Lady Davis Res Inst, Dept Oncol, Montreal, PQ H3T 1E2, Canada. [Rifai, Nader] Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. [Landgren, Ola] NCI, Multiple Myeloma Sect, Metab Branch,Ctr Canc Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Lessin, Lawrence] Howard Univ, MedStar Res Inst, Washington, DC 20059 USA. [Lessin, Lawrence] Washington Hosp Ctr, Washington Canc Inst, Dept Med Oncol & Hematol, Washington, DC 20010 USA. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Wallace, Robert B.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. [Colditz, Graham A.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Colditz, Graham A.] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA. [Colditz, Graham A.] Barnes Jewish Hosp, St Louis, MO 63110 USA. RP Birmann, BM (reprint author), Brigham & Womens Hosp, Channing Div Network Med, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM brenda.birmann@channing.harvard.edu RI Albanes, Demetrius/B-9749-2015; Purdue, Mark/C-9228-2016; Colditz, Graham/A-3963-2009; OI Purdue, Mark/0000-0003-1177-3108; Colditz, Graham/0000-0002-7307-0291; Giles, Graham/0000-0003-4946-9099 FU National Institutes of Health [R01 CA127435, K07 CA115687, P01 CA87969, R01 CA49449, P01 CA055075, P50 CA100707, CA047988, HL043851, HL080467, R01CA080205, R01CA144034]; National Cancer Institute Division of Cancer Epidemiology and Genetics; National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221] FX This work was supported by the National Institutes of Health (R01 CA127435, K07 CA115687, B.M.B.; P01 CA87969, R01 CA49449, P01 CA055075, P50 CA100707, CA047988, HL043851, HL080467, R01CA080205, and R01CA144034) and the National Cancer Institute Division of Cancer Epidemiology and Genetics (intramural funds). The WHI program is supported by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services (contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221). NR 50 TC 17 Z9 17 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 13 PY 2012 VL 120 IS 25 BP 4929 EP 4937 DI 10.1182/blood-2012-03-417253 PG 9 WC Hematology SC Hematology GA 065BR UT WOS:000313122800009 PM 23074271 ER PT J AU Blotta, S Jakubikova, J Calimeri, T Roccaro, AM Amodio, N Azab, AK Foresta, U Mitsiades, CS Rossi, M Todoerti, K Molica, S Morabito, F Neri, A Tagliaferri, P Tassone, P Anderson, KC Munshi, NC AF Blotta, Simona Jakubikova, Jana Calimeri, Teresa Roccaro, Aldo M. Amodio, Nicola Azab, Abdel Kareem Foresta, Umberto Mitsiades, Constantine S. Rossi, Marco Todoerti, Katia Molica, Stefano Morabito, Fortunato Neri, Antonino Tagliaferri, Piersandro Tassone, Pierfrancesco Anderson, Kenneth C. Munshi, Nikhil C. TI Canonical and noncanonical Hedgehog pathway in the pathogenesis of multiple myeloma SO BLOOD LA English DT Article ID STEM-CELL FUNCTION; SONIC HEDGEHOG; SIGNALING PATHWAY; DRUG-RESISTANCE; DENDRITIC CELLS; LEUKEMIA CELLS; CANCER; ACTIVATION; MEDULLOBLASTOMA; PROLIFERATION AB The Hedgehog (Hh) pathway is required for cell-fate determination during the embryonic life, as well as cell growth and differentiation in the adult organism, where the inappropriate activation has been implicated in several cancers. Here we demonstrate that Hh signaling plays a significant role in growth and survival of multiple myeloma (MM) cells. We observed that CD138(+) MM cells express Hh genes and confirmed Smoothened (Smo)-dependent Hh signaling in MM using a novel synthetic Smo inhibitor, NVP-LDE225 (Novartis), which decreased MM cell viability by inducing specific downregulation of Gli1 and Ptch1, hallmarks of Hh activity. In addition, we detected a nuclear localization of Gli1 in MM cells, which is completely abrogated by Forskolin, a Gli1-modulating compound, confirming Smo-independent mechanisms leading to Hh activation in MM. Finally, we identified that bone marrow stromal cells are a source of the Shh ligand, although they are resistant to the Hh inhibitor because of defective Smo expression and Ptch1 up-regulation. Further in vitro as well as in vivo studies showed antitumor efficacy of NVP-LDE225 in combination with bortezomib. Altogether, our data demonstrate activation of both canonical and noncanonical Hh pathway in MM, thus providing the rationale for testing Hh inhibitors in clinical trials to improve MM patient outcome. (Blood. 2012; 120(25): 5002-5013) C1 [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Blotta, Simona; Calimeri, Teresa; Munshi, Nikhil C.] Harvard Univ, Sch Med, Vet Adm Boston Healthcare Syst, Boston, MA USA. [Blotta, Simona; Calimeri, Teresa; Amodio, Nicola; Foresta, Umberto; Rossi, Marco; Tagliaferri, Piersandro; Tassone, Pierfrancesco] Magna Graecia Univ Catanzaro, Catanzaro, Italy. [Blotta, Simona; Calimeri, Teresa; Amodio, Nicola; Foresta, Umberto; Rossi, Marco; Tagliaferri, Piersandro; Tassone, Pierfrancesco] Ctr Canc, Catanzaro, Italy. [Blotta, Simona] Pugliese Ciaccio Hosp, Dept Hematol & Oncol, Catanzaro, Italy. [Jakubikova, Jana] Dept Tumor Immunol, Bratislava, Slovakia. [Jakubikova, Jana] VVCE CeXignal, Bratislava, Slovakia. [Todoerti, Katia; Neri, Antonino] Univ Milano Ematol 1, Fdn IRCCS Osped Policlin Milano, Dipartimento Sci Med, Milan, Italy. [Morabito, Fortunato] Cosenza Hosp, Hematol Unit, Cosenza, Italy. RP Munshi, NC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,M1B28, Boston, MA 02115 USA. EM nikhil_munshi@dfci.harvard.edu RI Amodio, Nicola/K-7335-2016; OI Amodio, Nicola/0000-0002-1345-4410; Todoerti, Katia/0000-0001-6687-6871; neri, antonino/0000-0001-9047-5912; Roccaro, Aldo/0000-0002-1872-5128; ROSSI, Marco/0000-0002-7258-475X FU National Institutes of Health [P50CA-100707, RO1-124929, PO1-155258, P50-100007, PO1-78378, RO1-50947]; Department of Veterans Affairs [I01-BX001584]; Italian Association for Cancer Research [9980]; Amgen; AVEO Pharma; OSI; EMD Serono; Sunesis; Genzyme; Johnson Johnson FX This work was supported by the Specialized Program of Research Excellence in Myeloma-National Institutes of Health (Career Development Award grant P50CA-100707, S.B.), Department of Veterans Affairs (Merit Review Award I01-BX001584), National Institutes of Health (grants RO1-124929 and PO1-155258, N.C.M.; grants P50-100007 and PO1-78378, N.C.M. and K.C.A.; and grant RO1-50947 to K.C.A. and C.S.M.), the American Cancer Society Clinical Research Professor (K.C.A.), and the Italian Association for Cancer Research (grant 9980, P.T.).; Conflict-of-interest disclosure: K.C.A. is on the advisory board of Celgene, Millennium, Onyx, and Bristol-Myers Squibb and is Scientific Founder of Acetylon and Oncopep. N.C.M. is on the advisory board of Celgene, Millennium, Onyx, and Merck and is Scientific Founder of Oncopep. C.S.M. received consultant honoraria from Millennium, Celgene, Novartis, Bristol-Myers Squibb, Merck & Co, Centocor, and Arno Therapeutics; he received research funding from Amgen, AVEO Pharma, OSI, EMD Serono, Sunesis, Genzyme, and Johnson & Johnson; and he has an uncompensated role as scientific advisor for Axios Biosciences. The remaining authors declare no competing financial interests. NR 49 TC 40 Z9 45 U1 0 U2 15 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 13 PY 2012 VL 120 IS 25 BP 5002 EP 5013 DI 10.1182/blood-2011-07-368142 PG 12 WC Hematology SC Hematology GA 065BR UT WOS:000313122800017 PM 22821765 ER PT J AU Huett, A Heath, RJ Begun, J Sassi, SO Baxt, LA Vyas, JM Goldberg, MB Xavier, RJ AF Huett, Alan Heath, Robert J. Begun, Jakob Sassi, Slim O. Baxt, Leigh A. Vyas, Jatin M. Goldberg, Marcia B. Xavier, Ramnik J. TI The LRR and RING Domain Protein LRSAM1 Is an E3 Ligase Crucial for Ubiquitin-Dependent Autophagy of Intracellular Salmonella Typhimurium SO CELL HOST & MICROBE LA English DT Article ID LEUCINE-RICH REPEAT; INTERACTION NETWORK; CONTAINING VACUOLE; IMPAIRED AUTOPHAGY; CELLS; BACTERIA; DISEASE; P62/SQSTM1; INFECTION; ATG16L1 AB Several species of pathogenic bacteria replicate within an intracellular vacuolar niche. Bacteria that escape into the cytosol are captured by the autophagic pathway and targeted for lysosomal degradation, representing a defense against bacterial exploitation of the host cytosol. Autophagic capture of Salmonella Typhimurium occurs predominantly via generation of a polyubiquitin signal around cytosolic bacteria, binding of adaptor proteins, and recruitment of autophagic machinery. However, the components mediating bacterial target selection and ubiquitination remain obscure. We identify LRSAM1 as the E3 ligase responsible for anti-Salmonella autophagy-associated ubiquitination. LRSAM1 localizes to several intracellular bacterial pathogens and generates the bacteria-associated ubiquitin signal; these functions require LRSAM1's leucine-rich repeat and RING domains, respectively. Using cells from LRSAM1 -deficient individuals, we confirm that LRSAM1 is required for ubiquitination associated with intracellular bacteria but dispensable for ubiquitination of aggregated proteins. LRSAM1 is therefore a bacterial recognition protein and ubiquitin ligase that defends the cytoplasm from invasive pathogens. C1 [Huett, Alan; Heath, Robert J.; Begun, Jakob; Sassi, Slim O.; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Huett, Alan; Heath, Robert J.; Begun, Jakob; Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Huett, Alan; Heath, Robert J.; Begun, Jakob; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Heath, Robert J.; Xavier, Ramnik J.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Sassi, Slim O.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Baxt, Leigh A.; Vyas, Jatin M.; Goldberg, Marcia B.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Cambridge, MA 02139 USA. RP Xavier, RJ (reprint author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. EM xavier@molbio.mgh.harvard.edu RI Begun, Jakob/J-6793-2014; Vyas, Jatin/Q-1627-2016 OI Begun, Jakob/0000-0001-5256-7672; Vyas, Jatin/0000-0002-9985-9565 FU National Institutes of Health [R01 DK083756, R01 DK060049, U01 DK062432, P30 DK043351]; Helmsley Trust; Crohn's and Colitis Foundation of America; Faculty of Medicine and Health Sciences, University of Nottingham FX The authors thank Karen Bedard, Felix Randow, and Conrad Weihl for the supply of reagents; Agnes Gardet, Skip Virgin, Mihai Netea, Joseph Avruch, and Felix Randow for discussions of the manuscript; Jenny Tam for microscopy advice; Lynda Stuart for assistance with deconvolution software; and Natalia Nedelsky for editorial assistance. NDP52 construction mutants were a gift from Felix Randow. R.J.X., A.H., J.B., and R.J.H. are funded by grants from the National Institutes of Health (R01 DK083756, R01 DK060049, U01 DK062432, and P30 DK043351 to R.J.X.), as well as grants from the Helmsley Trust and the Crohn's and Colitis Foundation of America. Additional funding was provided to A.H. by the Faculty of Medicine and Health Sciences, University of Nottingham. NR 34 TC 74 Z9 75 U1 1 U2 13 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 J9 CELL HOST MICROBE JI Cell Host Microbe PD DEC 13 PY 2012 VL 12 IS 6 BP 778 EP 790 DI 10.1016/j.chom.2012.10.019 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 069AF UT WOS:000313406600008 PM 23245322 ER PT J AU Schonbach, C Tongsima, S Chan, J Brusic, V Tan, TW Ranagathan, S AF Schoenbach, Christian Tongsima, Sissades Chan, Jonathan Brusic, Vladimir Tan, Tin Wee Ranagathan, Shoba TI InCoB2012 Conference: from biological data to knowledge to technological breakthroughs SO BMC BIOINFORMATICS LA English DT Editorial Material ID INTERNATIONAL-CONFERENCE; JOINT CONFERENCE; ASIA-PACIFIC; BIOINFORMATICS; IMMUNOLOGY; PREDICTION; PEPTIDES; DECADE AB Ten years ago when Asia-Pacific Bioinformatics Network held the first International Conference on Bioinformatics (InCoB) in Bangkok its theme was North-South Networking. At that time InCoB aimed to provide biologists and bioinformatics researchers in the Asia-Pacific region a forum to meet, interact with, and disseminate knowledge about the burgeoning field of bioinformatics. Meanwhile InCoB has evolved into a major regional bioinformatics conference that attracts not only talented and established scientists from the region but increasingly also from East Asia, North America and Europe. Since 2006 InCoB yielded 114 articles in BMC Bioinformatics supplement issues that have been cited nearly 1,000 times to date. In part, these developments reflect the success of bioinformatics education and continuous efforts to integrate and utilize bioinformatics in biotechnology and biosciences in the Asia-Pacific region. A cross-section of research leading from biological data to knowledge and to technological applications, the InCoB2012 theme, is introduced in this editorial. Other highlights included sessions organized by the Pan-Asian Pacific Genome Initiative and a Machine Learning in Immunology competition. InCoB2013 is scheduled for September 18-21, 2013 at Suzhou, China. C1 [Schoenbach, Christian] Kyushu Inst Technol, Dept Biosci & Bioinformat, Fukuoka 8208502, Japan. [Schoenbach, Christian] Kyushu Inst Technol, Biomed Informat Res & Dev Ctr, Fukuoka 8208502, Japan. [Tongsima, Sissades] Natl Sci & Technol Dev Agcy, Natl Ctr Genet Engn & Biotechnol BIOTEC, Pathum Thani 12120, Thailand. [Chan, Jonathan] King Mongkuts Univ Technol Thonburi, Sch Informat Technol, Bangkok 10140, Thailand. [Brusic, Vladimir] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Tan, Tin Wee; Ranagathan, Shoba] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore 117597, Singapore. [Tan, Tin Wee] ASTAR, Computat Resource Ctr A CRC, Singapore 138632, Singapore. [Ranagathan, Shoba] Macquarie Univ, Dept Chem & Biomol Sci, Sydney, NSW 2109, Australia. [Ranagathan, Shoba] Macquarie Univ, ARC Ctr Excellence, Sydney, NSW 2109, Australia. RP Schonbach, C (reprint author), Kyushu Inst Technol, Dept Biosci & Bioinformat, Fukuoka 8208502, Japan. EM schoen@bio.kyutech.ac.jp; shoba.ranganathan@mq.edu.au RI Tan, Tin Wee/B-8963-2009; Schonbach, Christian/B-1998-2009; OI Tan, Tin Wee/0000-0002-4062-2854; Schonbach, Christian/0000-0002-0693-7617; Ranganathan, Shoba/0000-0002-8290-813X NR 40 TC 2 Z9 2 U1 1 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD DEC 13 PY 2012 VL 13 SU 17 AR S1 DI 10.1186/1471-2105-13-S17-S1 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 063GV UT WOS:000312985100001 PM 23281929 ER PT J AU Zhuang, K Finzi, A Toma, J Frantzell, A Huang, W Sodroski, J Cheng-Mayer, C AF Zhuang, Ke Finzi, Andres Toma, Jonathan Frantzell, Arne Huang, Wei Sodroski, Joseph Cheng-Mayer, Cecilia TI Identification of interdependent variables that influence coreceptor switch in R5 SHIVSF162P3N-infected macaques SO RETROVIROLOGY LA English DT Article DE R5 SHIV; Coreceptor switch; CD4 binding; Macrophage infection ID HUMAN-IMMUNODEFICIENCY-VIRUS; TREATMENT-EXPERIENCED PATIENTS; SYNCYTIUM-INDUCING PHENOTYPE; INCREASED NEUTRALIZATION SENSITIVITY; MONOCYTE-DERIVED MACROPHAGES; ENVELOPE V3 LOOP; CD4(+) T-CELLS; SOLUBLE CD4; INFECTED MACAQUES; TYPE-1 INFECTION AB Background: We previously reported that adoption of an "open" envelope glycoprotein (Env) to expose the CD4 binding site for efficient receptor binding and infection of cell targets such as macrophages that express low levels of the receptor represents an early event in the process of coreceptor switch in two rapidly progressing (RP) R5 SHIVSF162P3N-infected rhesus macaques, releasing or reducing Env structural constraints that have been suggested to limit the pathways available for a change in coreceptor preference. Here we extended these studies to two additional RP monkeys with coreceptor switch and three without to confirm and identify additional factors that facilitated the process of phenotypic conversion. Results: We found that regardless of coreceptor switching, R5 viruses in SHIVSF162P3N-infected RP macaques evolved over time to infect macrophages more efficiently; this was accompanied by increased sCD4 sensitivity, with structural changes in the CD4 binding site, the V3 loop and/or the fusion domain of their Envs that are suggestive of better CD4 contact, CCR5 usage and/or virus fusion. However, sCD4-sensitive variants with improved CD4 binding were observed only in RPs with coreceptor switch. Furthermore, cumulative viral load was higher in RPs with than in those without phenotypic switch, with the latter maintaining a longer period of seroconversion. Conclusions: Our data suggest that the increased virus replication in the RPs with R5-to-X4 conversion increased the rate of virus evolution and reduction in the availability of target cells with optimal CD4 expression heightened the competition for binding to the receptor. In the absence of immunological restrictions, variants that adopt an "open" Env to expose the CD4 binding site for better CD4 use are selected, allowing structural changes that confer CXCR4-use to be manifested. Viral load, change in target cell population during the course of infection and host immune response therefore are interdependent variables that influence R5 virus evolution and coreceptor switch in SHIVSF162P3N-infected rhesus macaques. Because an "open" Env conformation also renders the virus more susceptible to antibody neutralization, our findings help to explain the infrequent and late appearance of X4 virus in HIV-1 infection when the immune system deteriorates. C1 [Zhuang, Ke; Cheng-Mayer, Cecilia] Aaron Diamond AIDS Res Ctr, New York, NY USA. [Finzi, Andres] Univ Montreal, Ctr Rech, CHUM, Montreal, PQ, Canada. [Toma, Jonathan; Frantzell, Arne; Huang, Wei] Monogram Biosci Inc, San Francisco, CA USA. [Sodroski, Joseph] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cheng-Mayer, C (reprint author), Aaron Diamond AIDS Res Ctr, New York, NY USA. EM cmayer@adarc.org FU National Institutes of Health [RO1AI084765] FX We thank William Olsen for PRO542, Oliver Hartley for PSC-RANTES, Dennis Burton and Susan Zolla-Pazner for the IgGb12 and 447-52D antibody, respectively, Shibo Jiang for T20, and Hiroshi Mohri for help with statistical analysis. TZM-bl cells (catalog no. 8129 from John C Kappes, Xiaoyun Wu and Tranzyme, Inc.) were obtained through the NIH AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH. This work was supported by the National Institutes of Health grants RO1AI084765. NR 89 TC 7 Z9 7 U1 0 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD DEC 13 PY 2012 VL 9 AR 106 DI 10.1186/1742-4690-9-106 PG 14 WC Virology SC Virology GA 057RX UT WOS:000312582800001 PM 23237529 ER PT J AU Adachi, LNS Caumo, W Laste, G Medeiros, LF Rozisky, JR de Souza, A Fregni, F Torres, ILS AF Spezia Adachi, Lauren Naomi Caumo, Wolnei Laste, Gabriela Medeiros, Liciane Fernandes Rozisky, Joanna Ripoll de Souza, Andressa Fregni, Felipe Torres, Iraci L. S. TI Reversal of chronic stress-induced pain by transcranial direct current stimulation (tDCS) in an animal model SO BRAIN RESEARCH LA English DT Article DE Chronic restraint stress; Hyperalgesia; Allodynia; Transcranial direct current stimulation (tDCS); Neuromodulation; TNF alpha ID HUMAN MOTOR CORTEX; NONINVASIVE BRAIN-STIMULATION; REPEATED RESTRAINT STRESS; DC-STIMULATION; INDUCED ANTINOCICEPTION; CORTICAL EXCITABILITY; FIBROMYALGIA SYNDROME; ALTERNATING-CURRENT; HEALTHY-SUBJECTS; SPINAL-CORD AB Transcranial direct current stimulation (tDCS) has been suggested as a therapeutic tool for pain syndromes. Although initial results in human subjects are encouraging, it still remains unclear whether the effects of tDCS can reverse maladaptive plasticity associated with chronic pain. To investigate this question, we tested whether tDCS can reverse the specific behavioral effects of chronic stress in the pain system, and also those indexed by corticosterone and interleukin-1 beta levels in serum and TNF alpha levels in the hippocampus, in a well-controlled rat model of chronic restraint stress (CRS). Forty-one adult male Wistar rats were divided into two groups control and stress. The stress group was exposed to CRS for 11 weeks for the establishment of hyperalgesia and mechanical allodynia as shown by the hot plate and von Frey tests, respectively. Rats were then divided into four groups control, stress, stress+sham tDCS and stress+tDCS. Anodal or sham tDCS was applied for 20 min/day over 8 days and the tests were repeated. Then, the animals were killed, blood collected and hippocampus removed for ELISA testing. This model of CRS proved effective to induce chronic pain, as the animals exhibited hyperalgesia and mechanical allodynia. The hot plate test showed an analgesic effect, and the von Frey test, an anti-allodynic effect after the last tDCS session, and there was a significant decrease in hippocampal TNF alpha levels. These results support the notion that tDCS reverses the detrimental effects of chronic stress on the pain system and decreases TNF alpha levels in the hippocampus. (c) 2012 Elsevier B.V. All rights reserved. C1 [Torres, Iraci L. S.] Univ Fed Rio Grande do Sul, Dept Farmacol, ICBS, Pain Pharmacol & Neuromodulat Anim Models Lab, BR-90050170 Porto Alegre, RS, Brazil. [Spezia Adachi, Lauren Naomi; Caumo, Wolnei; Laste, Gabriela; Rozisky, Joanna Ripoll; de Souza, Andressa; Torres, Iraci L. S.] Univ Fed Rio Grande do Sul, Grad Program Med Sci, BR-90035003 Porto Alegre, RS, Brazil. [Spezia Adachi, Lauren Naomi; Laste, Gabriela; Medeiros, Liciane Fernandes; Rozisky, Joanna Ripoll; de Souza, Andressa; Torres, Iraci L. S.] Hosp Clin Porto Alegre, Anim Experimentat Unit, BR-90035003 Porto Alegre, RS, Brazil. [Spezia Adachi, Lauren Naomi; Laste, Gabriela; Medeiros, Liciane Fernandes; Rozisky, Joanna Ripoll; de Souza, Andressa; Torres, Iraci L. S.] Hosp Clin Porto Alegre, Grad Res Grp, BR-90035003 Porto Alegre, RS, Brazil. [Fregni, Felipe] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Lab Neuromodulat, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Noninvas Brain Stimulat, Boston, MA 02215 USA. RP Torres, ILS (reprint author), Univ Fed Rio Grande do Sul, Dept Farmacol, ICBS, Pain Pharmacol & Neuromodulat Anim Models Lab, Rua Sarmento Leite,500 Sala 202, BR-90050170 Porto Alegre, RS, Brazil. EM lauren_adachi@hotmail.com; caumo@cpovo.net; gabrielalaste@gmail.com; licimedeiros@hotmail.com; joannarozisky@gmail.com; andressasz@gmail.com; fregni.felipe@mgh.harvard.edu; iracitorres@gmail.com RI Laste, Gabriela/A-3033-2014; Medeiros, Liciane/A-3626-2014; Torres, iraci/G-6693-2012; Rozisky, Joanna/F-6584-2015 OI Torres, iraci/0000-0002-3081-115X; FU National Council for Scientific and Technological Development-CNPq; Committee for the Development of Higher Education Personnel-CAPES; Graduate Research Group (GPPG) of Hospital de Clinicas de Porto Alegre-HCPA [100381] FX This research was supported by the following Brazilian funding agencies: National Council for Scientific and Technological Development-CNPq (I.L.S. Torres, W. Caumo); Committee for the Development of Higher Education Personnel-CAPES (J.R. Rozisky, A. Souza, G. Laste, L.N.S. Adachi, L.F. Medeiros); Graduate Research Group (GPPG) of Hospital de Clinicas de Porto Alegre-HCPA (I.L.S. Torres - Grant 100381). Our acknowledgments to engineering from the HCPA for have developed the tDCS stimulator. NR 75 TC 11 Z9 12 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD DEC 13 PY 2012 VL 1489 BP 17 EP 26 DI 10.1016/j.brainres.2012.10.009 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 054PZ UT WOS:000312357000003 ER PT J AU Bart, BA Goldsmith, SR Lee, KL Givertz, MM O'Connor, CM Bull, DA Redfield, MM Deswal, A Rouleau, JL LeWinter, MM Ofili, EO Stevenson, LW Semigran, MJ Felker, GM Chen, HH Hernandez, AF Anstrom, KJ McNulty, SE Velazquez, EJ Ibarra, JC Mascette, AM Braunwald, E AF Bart, Bradley A. Goldsmith, Steven R. Lee, Kerry L. Givertz, Michael M. O'Connor, Christopher M. Bull, David A. Redfield, Margaret M. Deswal, Anita Rouleau, Jean L. LeWinter, Martin M. Ofili, Elizabeth O. Stevenson, Lynne W. Semigran, Marc J. Felker, G. Michael Chen, Horng H. Hernandez, Adrian F. Anstrom, Kevin J. McNulty, Steven E. Velazquez, Eric J. Ibarra, Jenny C. Mascette, Alice M. Braunwald, Eugene CA Heart Failure Clinical Res Network TI Ultrafiltration in Decompensated Heart Failure with Cardiorenal Syndrome SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID WORSENING RENAL-FUNCTION; HOSPITALIZED-PATIENTS; DIURETICS; CONGESTION; OVERLOAD AB BACKGROUND Ultrafiltration is an alternative strategy to diuretic therapy for the treatment of patients with acute decompensated heart failure. Little is known about the efficacy and safety of ultrafiltration in patients with acute decompensated heart failure complicated by persistent congestion and worsened renal function. METHODS We randomly assigned a total of 188 patients with acute decompensated heart failure, worsened renal function, and persistent congestion to a strategy of stepped pharmacologic therapy (94 patients) or ultrafiltration (94 patients). The primary end point was the bivariate change from baseline in the serum creatinine level and body weight, as assessed 96 hours after random assignment. Patients were followed for 60 days. RESULTS Ultrafiltration was inferior to pharmacologic therapy with respect to the bivariate end point of the change in the serum creatinine level and body weight 96 hours after enrollment (P = 0.003), owing primarily to an increase in the creatinine level in the ultrafiltration group. At 96 hours, the mean change in the creatinine level was -0.04 +/- 0.53 mg per deciliter (-3.5 +/- 46.9 mu mol per liter) in the pharmacologictherapy group, as compared with +0.23 +/- 0.70 mg per deciliter (20.3 +/- 61.9 mu mol per liter) in the ultrafiltration group (P = 0.003). There was no significant difference in weight loss 96 hours after enrollment between patients in the pharmacologic-therapy group and those in the ultrafiltration group (a loss of 5.5 +/- 5.1 kg [12.1 +/- 11.3 lb] and 5.7 +/- 3.9 kg [12.6 +/- 8.5 lb], respectively; P = 0.58). A higher percentage of patients in the ultrafiltration group than in the pharmacologic-therapy group had a serious adverse event (72% vs. 57%, P = 0.03). CONCLUSIONS In a randomized trial involving patients hospitalized for acute decompensated heart failure, worsened renal function, and persistent congestion, the use of a stepped pharmacologic-therapy algorithm was superior to a strategy of ultrafiltration for the preservation of renal function at 96 hours, with a similar amount of weight loss with the two approaches. Ultrafiltration was associated with a higher rate of adverse events. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00608491.) C1 [Bart, Bradley A.; Goldsmith, Steven R.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. [Redfield, Margaret M.; Chen, Horng H.] Mayo Clin, Rochester, MN USA. [Lee, Kerry L.; Hernandez, Adrian F.; Anstrom, Kevin J.; McNulty, Steven E.; Velazquez, Eric J.; Ibarra, Jenny C.] Duke Clin Res Inst, Durham, NC USA. [O'Connor, Christopher M.; Felker, G. Michael] Duke Univ, Med Ctr, Durham, NC USA. [O'Connor, Christopher M.; Felker, G. Michael] Duke Univ, Med Ctr, Duke Heart Ctr, Durham, NC 27710 USA. [Givertz, Michael M.; Stevenson, Lynne W.; Braunwald, Eugene] Brigham & Womens Hosp, Boston, MA 02115 USA. [Semigran, Marc J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bull, David A.] Univ Utah, Salt Lake City, UT USA. [Deswal, Anita] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Deswal, Anita] Baylor Coll Med, Houston, TX 77030 USA. [Rouleau, Jean L.] Univ Montreal, Montreal, PQ, Canada. [Rouleau, Jean L.] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [LeWinter, Martin M.] Univ Vermont, Burlington, VT 05405 USA. [Ofili, Elizabeth O.] Morehouse Sch Med, Atlanta, GA 30310 USA. [Mascette, Alice M.] NHLBI, Bethesda, MD 20892 USA. RP Bart, BA (reprint author), O5 HCMC,701 Pk Ave S, Minneapolis, MN 55410 USA. EM bartx006@umn.edu RI Hernandez, Adrian F./A-7818-2016 OI Hernandez, Adrian F./0000-0003-3387-9616 FU National Heart, Lung, and Blood Institute [U10HL084904, U10HL084861, U10HL084875, U10HL084877, U10HL084889, U10HL084890, U10HL084891, U10HL084899, U10HL084907, U10HL084931] FX Supported by grants from the National Heart, Lung, and Blood Institute (U10HL084904 [for the data coordinating center], U10HL084861, U10HL084875, U10HL084877, U10HL084889, U10HL084890, U10HL084891, U10HL084899, U10HL084907, and U10HL084931 [for the clinical centers]). NR 24 TC 233 Z9 256 U1 3 U2 24 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 13 PY 2012 VL 367 IS 24 BP 2296 EP 2304 DI 10.1056/NEJMoa1210357 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 052HF UT WOS:000312187700003 PM 23131078 ER PT J AU Stone, JH Patel, VI Oliveira, GR Stone, JR AF Stone, John H. Patel, Virendra I. Oliveira, George R. Stone, James R. TI Case 38-2012: A 60-Year-Old Man with Abdominal Pain and Aortic Aneurysms SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID IGG4-RELATED SYSTEMIC-DISEASE; SURGICAL PATHOLOGY; LYMPHOPLASMACYTIC AORTITIS; RELAPSING POLYCHONDRITIS; ANKYLOSING-SPONDYLITIS; CONSENSUS STATEMENT; INFLAMED CARTILAGE; SCLEROSING DISEASE; ASCENDING AORTA; BEHCETS-DISEASE C1 [Stone, John H.] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Patel, Virendra I.] Massachusetts Gen Hosp, Dept Surg, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. [Oliveira, George R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Stone, James R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Stone, John H.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Patel, Virendra I.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Oliveira, George R.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Stone, James R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. FU Genentech; GlaxoSmithKline; Merck FX Dr. John H. Stone reports receiving grant support from Genentech, and Dr. James R. Stone receiving consulting fees from GlaxoSmithKline and Merck and providing paid expert testimony for GlaxoSmithKline regarding rosiglitazone. No other potential conflict of interest relevant to this article was reported. NR 49 TC 12 Z9 13 U1 0 U2 9 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 13 PY 2012 VL 367 IS 24 BP 2335 EP 2346 DI 10.1056/NEJMcpc1209330 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 052HF UT WOS:000312187700009 PM 23234517 ER PT J AU Schwartzman, WA AF Schwartzman, William A. TI Mycobacterium chelonae Illnesses Associated with Tattoo Ink SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID OUTBREAK C1 Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Schwartzman, WA (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. EM william.schwartzman@va.gov NR 2 TC 2 Z9 2 U1 0 U2 6 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 13 PY 2012 VL 367 IS 24 BP 2356 EP 2357 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 052HF UT WOS:000312187700021 PM 23234523 ER PT J AU Grenon, SM Saary, J Gray, G Vanderploeg, JM Hughes-Fulford, M AF Grenon, S. Marlene Saary, Joan Gray, Gary Vanderploeg, James M. Hughes-Fulford, Millie TI Can I take a space flight? Considerations for doctors SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID HUMAN SPACEFLIGHT AB Commercial investment is bringing space tourism closer to reality. Marlene Grenon and colleagues outline what doctors will need to know Although perhaps unfamiliar with the specific physiological changes associated with commercial air travel, most physicians will have travelled by plane and many will have attended a passenger in need of medical assistance while on a commercial flight. They are, however, unlikely to have experience of space travel. Numerous commercial enterprises exist that will eventually provide competitively priced access to spaceflight experiences for paying customers. With spaceports construction under way, bookings are already taking place. Physicians can in future expect patients to ask questions and request clearance processes (such as fitness to fly certificates) for space travel as they do for commercial airplane flights today. Here, we provide some background to the field of space medicine for non-experts and point to resources for clinicians when a patient presents with requests related to space travel. C1 [Grenon, S. Marlene] Univ Calif San Francisco, Div Vasc & Endovasc Surg, San Francisco, CA 94121 USA. [Grenon, S. Marlene] San Francisco VA Med Ctr, Dept Surg, San Francisco, CA USA. [Saary, Joan] Univ Toronto, Dept Occupat Med, Toronto, ON, Canada. [Saary, Joan] Canadian Forces Environm Med Estab, Toronto, ON, Canada. [Gray, Gary] Canadian Space Agcy, Montreal, PQ, Canada. [Vanderploeg, James M.] Univ Texas Med Branch, Dept Prevent Med & Community Hlth, Aerosp Med Program, Galveston, TX USA. [Hughes-Fulford, Millie] Vet Affairs Med Ctr, Hughes Fulford Lab, San Francisco, CA 94121 USA. [Hughes-Fulford, Millie] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. RP Grenon, SM (reprint author), Univ Calif San Francisco, Div Vasc & Endovasc Surg, San Francisco, CA 94121 USA. EM marlene.grenon@ucsfmedctr.org FU NCRR NIH HHS [KL2RR024130]; NIA NIH HHS [UH3 AG037628] NR 22 TC 7 Z9 7 U1 3 U2 9 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BRIT MED J JI Br. Med. J. PD DEC 13 PY 2012 VL 345 AR e8124 DI 10.1136/bmj.e8124 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 056MZ UT WOS:000312495700005 PM 23241271 ER PT J AU Chen, X Threlkeld, SW Cummings, EE Juan, I Makeyev, O Besio, WG Gaitanis, J Banks, WA Sadowska, GB Stonestreet, BS AF Chen, X. Threlkeld, S. W. Cummings, E. E. Juan, I. Makeyev, O. Besio, W. G. Gaitanis, J. Banks, W. A. Sadowska, G. B. Stonestreet, B. S. TI ISCHEMIA-REPERFUSION IMPAIRS BLOOD-BRAIN BARRIER FUNCTION AND ALTERS TIGHT JUNCTION PROTEIN EXPRESSION IN THE OVINE FETUS SO NEUROSCIENCE LA English DT Article DE blood-brain barrier; brain; fetus; ischemia-reperfusion; ovine; tight junction proteins ID CEREBRAL-ARTERY OCCLUSION; NEWBORN PIGLETS; FOCAL ISCHEMIA; PERMEABILITY; INJURY; RATS; LAMBS; DISRUPTION; TRANSPORT; CORTEX AB The blood-brain barrier is a restrictive interface between the brain parenchyma and the intravascular compartment. Tight junctions contribute to the integrity of the blood-brain barrier. Hypoxic-ischemic damage to the blood-brain barrier could be an important component of fetal brain injury. We hypothesized that increases in blood-brain barrier permeability after ischemia depend upon the duration of reperfusion and that decreases in tight junction proteins are associated with the ischemia-related impairment in blood-brain barrier function in the fetus. Blood-brain barrier function was quantified with the blood-to-brain transfer constant (K-i) and tight junction proteins by Western immunoblot in fetal sheep at 127 days of gestation without ischemia, and 4, 24, or 48 h after ischemia. The largest increase in K-i (P < 0.05) was 4 h after ischemia. Occludin and claudin-5 expressions decreased at 4 h, but returned toward control levels 24 and 48 h after ischemia. Zonula occludens-1 and -2 decreased after ischemia. Inverse correlations between Ki and tight junction proteins suggest that the decreases in tight junction proteins contribute to impaired blood-brain barrier function after ischemia. We conclude that impaired blood-brain barrier function is an important component of hypoxic-ischemic brain injury in the fetus, and that increases in quantitatively measured barrier permeability (K-i) change as a function of the duration of reperfusion after ischemia. The largest increase in permeability occurs 4 h after ischemia and blood-brain barrier function improves early after injury because the blood-brain barrier is less permeable 24 and 48 than 4 h after ischemia. Changes in the tight junction molecular composition are associated with increases in blood-brain barrier permeability after ischemia. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Chen, X.; Threlkeld, S. W.; Cummings, E. E.; Juan, I.; Sadowska, G. B.; Stonestreet, B. S.] Brown Univ, Alpert Med Sch, Dept Pediat, Women & Infants Hosp Rhode Isl, Providence, RI 02905 USA. [Makeyev, O.; Besio, W. G.] Univ Rhode Isl, Dept Elect Comp & Biomed Engn, Kingston, RI 02881 USA. [Gaitanis, J.] Brown Univ, Rhode Isl Hosp, Alpert Med Sch, Dept Neurol, Providence, RI 02903 USA. [Banks, W. A.] Univ Washington, Dept Internal Med, Geriatr Res Educ & Clin Ctr, Vet Affairs Puget Sound Hlth Care Syst,Div Geront, Seattle, WA 98108 USA. RP Stonestreet, BS (reprint author), Brown Univ, Alpert Med Sch, Dept Pediat, Women & Infants Hosp Rhode Isl, 101 Dudley St, Providence, RI 02905 USA. EM bstonestreet@wihri.org RI Chen, Xiaodi/C-9969-2013 FU NCRR NIH HHS [P20 RR016457, P20RR016457-11]; NICHD NIH HHS [1R01-HD-057100, R01 HD057100] NR 47 TC 18 Z9 18 U1 1 U2 21 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD DEC 13 PY 2012 VL 226 BP 89 EP 100 DI 10.1016/j.neuroscience.2012.08.043 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 047TT UT WOS:000311865100010 PM 22986172 ER PT J AU Narayan, N Lee, IH Borenstein, R Sun, JH Wong, R Tong, G Fergusson, MM Liu, J Rovira, II Cheng, HL Wang, GH Gucek, M Lombard, D Alt, FW Sack, MN Murphy, E Cao, L Finkel, T AF Narayan, Nisha Lee, In Hye Borenstein, Ronen Sun, Junhui Wong, Renee Tong, Guang Fergusson, Maria M. Liu, Jie Rovira, Ilsa I. Cheng, Hwei-Ling Wang, Guanghui Gucek, Marjan Lombard, David Alt, Fredrick W. Sack, Michael N. Murphy, Elizabeth Cao, Liu Finkel, Toren TI The NAD-dependent deacetylase SIRT2 is required for programmed necrosis (Retracted article. See vol. 506, pg. 516, 2014) SO NATURE LA English DT Article; Retracted Publication ID INDUCED CELL-DEATH; RIP1; APOPTOSIS; AUTOPHAGY; PHOSPHORYLATION; IDENTIFICATION; NECROPTOSIS; ACTIVATION; MECHANISMS; REGULATOR AB Although initially viewed as unregulated, increasing evidence suggests that cellular necrosis often proceeds through a specific molecular program. In particular, death ligands such as tumour necrosis factor (TNF)-alpha activate necrosis by stimulating the formation of a complex containing receptor-interacting protein 1 (RIP1) and receptor-interacting protein 3 (RIP3). Relatively little is known regarding how this complex formation is regulated. Here, we show that the NAD-dependent deacetylase SIRT2 binds constitutively to RIP3 and that deletion or knockdown of SIRT2 prevents formation of the RIP1-RIP3 complex in mice. Furthermore, genetic or pharmacological inhibition of SIRT2 blocks cellular necrosis induced by TNF-alpha. We further demonstrate that RIP1 is a critical target of SIRT2-dependent deacetylation. Using gain- and loss-of-function mutants, we demonstrate that acetylation of RIP1 lysine 530 modulates RIP1-RIP3 complex formation and TNF-alpha-stimulated necrosis. In the setting of ischaemia-reperfusion injury, RIP1 is deacetylated in a SIRT2-dependent fashion. Furthermore, the hearts of Sirt2(-/-) mice, or wild-type mice treated with a specific pharmacological inhibitor of SIRT2, show marked protection from ischaemic injury. Taken together, these results implicate SIRT2 as an important regulator of programmed necrosis and indicate that inhibitors of this deacetylase may constitute a novel approach to protect against necrotic injuries, including ischaemic stroke and myocardial infarction. C1 [Narayan, Nisha; Lee, In Hye; Borenstein, Ronen; Fergusson, Maria M.; Liu, Jie; Rovira, Ilsa I.; Sack, Michael N.; Finkel, Toren] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA. [Sun, Junhui; Wong, Renee; Tong, Guang; Murphy, Elizabeth] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. [Tong, Guang] Fourth Mil Med Univ, Xijing Hosp, Dept Cardiovasc Surg, Xian 710032, Peoples R China. [Cheng, Hwei-Ling; Alt, Fredrick W.] Childrens Hosp, Howard Hughes Med Inst, Program Cellular & Mol Med, Boston, MA 02115 USA. [Cheng, Hwei-Ling; Alt, Fredrick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Cheng, Hwei-Ling; Alt, Fredrick W.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Wang, Guanghui; Gucek, Marjan] NHLBI, Prote Core, NIH, Bethesda, MD 20892 USA. [Lombard, David] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Lombard, David] Univ Michigan, Inst Gerontol, Ann Arbor, MI 48109 USA. [Cao, Liu] China Med Univ, Key Lab Med Cell Biol, Shenyang 110001, Peoples R China. RP Finkel, T (reprint author), NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA. EM finkelt@nih.gov FU NIH FX We are grateful to M. Lenardo for providing the RIP1-deficient Jurkat cell line, X. Wang for the Flag-tagged RIP3 plasmid and Y. Zhao for helpful discussions. This work was supported by NIH Intramural funds. F.W.A. is an Investigator of the Howard Hughes Medical Institute. NR 32 TC 81 Z9 85 U1 3 U2 86 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD DEC 13 PY 2012 VL 492 IS 7428 BP 199 EP + DI 10.1038/nature11700 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 053GM UT WOS:000312259300031 PM 23201684 ER PT J AU Holmes, AJ Lee, PH Hollinshead, MO Bakst, L Roffman, JL Smoller, JW Buckner, RL AF Holmes, Avram J. Lee, Phil H. Hollinshead, Marisa O. Bakst, Leah Roffman, Joshua L. Smoller, Jordan W. Buckner, Randy L. TI Individual Differences in Amygdala-Medial Prefrontal Anatomy Link Negative Affect, Impaired Social Functioning, and Polygenic Depression Risk SO JOURNAL OF NEUROSCIENCE LA English DT Article ID ANTERIOR CINGULATE CORTEX; GENOME-WIDE ASSOCIATION; HUMAN CEREBRAL-CORTEX; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; GENDER-DIFFERENCES; MAJOR DEPRESSION; GENETIC-VARIATION; MOOD DISORDERS; BEHAVIORAL-INHIBITION; SEROTONIN TRANSPORTER AB Individual differences in affective and social processes may arise from variability in amygdala-medial prefrontal (mPFC) circuitry and related genetic heterogeneity. To explore this possibility in humans, we examined the structural correlates of trait negative affect in a sample of 1050 healthy young adults with no history of psychiatric illness. Analyses revealed that heightened negative affect was associated with increased amygdala volume and reduced thickness in a left mPFC region encompassing the subgenual and rostral anterior cingulate cortex. The most extreme individuals displayed an inverse correlation between amygdala volume and mPFC thickness, suggesting that imbalance between these structures is linked to negative affect in the general population. Subgroups of participants were further evaluated on social (n = 206) and emotional (n = 533) functions. Individuals with decreased mPFC thickness exhibited the poorest social cognition and were least able to correctly identify facial emotion. Given prior links between disrupted amygdala-mPFC circuitry and the presence of major depressive disorder (MDD), we explored whether the individual differences in anatomy observed here in healthy young adults were associated with polygenic risk for MDD (n = 438) using risk scores derived from a large genome-wide association analysis (n = 18,759). Analyses revealed associations between increasing polygenic burden for MDD and reduced cortical thickness in the left mPFC. These collective findings suggest that, within the healthy population, there is significant variability in amygdala-mPFC circuitry that is associated with poor functioning across affective and social domains. Individual differences in this circuitry may arise, in part, from common genetic variability that contributes to risk for MDD. C1 [Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Richard B Simches Res Ctr, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Holmes, Avram J.; Hollinshead, Marisa O.; Bakst, Leah; Buckner, Randy L.] Harvard Univ, Dept Psychol, Ctr Brain Sci, Cambridge, MA 02138 USA. [Holmes, Avram J.; Hollinshead, Marisa O.; Buckner, Randy L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Lee, Phil H.; Roffman, Joshua L.; Smoller, Jordan W.; Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Lee, Phil H.; Roffman, Joshua L.; Smoller, Jordan W.; Buckner, Randy L.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hollinshead, Marisa O.; Buckner, Randy L.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. RP Smoller, JW (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Richard B Simches Res Ctr, Psychiat & Neurodev Genet Unit, 185 Cambridge St, Boston, MA 02114 USA. EM jsmoller@hms.harvard.edu; randy_buckner@harvard.edu FU Simons Foundation; Howard Hughes Medical Institute; NIMH [R01-MH079799, K24MH094614]; NIMH grant [U01 MH085520] FX This work was supported by funding from the Simons Foundation (R.L.B.), the Howard Hughes Medical Institute (R.L.B.), and NIMH Grants R01-MH079799 (J.W.S.) and K24MH094614 (J.W.S.). The PGC analyses were supported by NIMH grant U01 MH085520 and polygene score data were obtained from http://www.broadinstitute.org/mpg/ricopili/. We are grateful to the Psychiatric Genomics Consortium, Wellcome Trust Case-Control Consortium, and DIAGRAM Consortium for sharing their genetic data analysis results. We thank Justin Baker, Eun Young Choi, Amitai Shenhav, and B. T. Thomas Yeo for their feedback on early versions of this manuscript; Timothy O'Keefe, Victor Petrov, and Gabriele Fariello for neuroinformatics; and the Harvard Center for Brain Science and the Athinoula A. Martinos Center for Biomedical Imaging for imaging support. The data were collected as part of the Brain Genomics Superstruct Project. NR 105 TC 62 Z9 65 U1 5 U2 28 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 12 PY 2012 VL 32 IS 50 BP 18087 EP 18100 DI 10.1523/JNEUROSCI.2531-12.2012 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 055GY UT WOS:000312404700016 PM 23238724 ER PT J AU Hall, DE Prochazka, AV Fink, AS AF Hall, Daniel E. Prochazka, Allan V. Fink, Aaron S. TI Perspectives on consent response SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Letter C1 [Hall, Daniel E.] Univ Pittsburgh, Ctr Hlth Equity Res & Promot, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. [Hall, Daniel E.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Prochazka, Allan V.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Prochazka, Allan V.] Univ Colorado, Sch Med, Dept Med, Aurora, CO USA. [Fink, Aaron S.] Vet Affairs Med Ctr Atlanta, Surg Serv, Decatur, GA USA. [Fink, Aaron S.] Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA. RP Hall, DE (reprint author), Univ Pittsburgh, Ctr Hlth Equity Res & Promot, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. RI Hall, Daniel/H-4843-2013; OI Hall, Daniel/0000-0001-6382-0522 NR 4 TC 0 Z9 0 U1 0 U2 0 PU CMA-CANADIAN MEDICAL ASSOC PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 5W8, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD DEC 11 PY 2012 VL 184 IS 18 BP 2019 EP 2019 DI 10.1503/cmaj.112-2091 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 077SW UT WOS:000314049200054 ER PT J AU Jones, CN Dalli, J Dimisko, L Wong, E Serhan, CN Irimia, D AF Jones, Caroline N. Dalli, Jesmond Dimisko, Laurie Wong, Elisabeth Serhan, Charles N. Irimia, Daniel TI Microfluidic chambers for monitoring leukocyte trafficking and humanized nano-proresolving medicines interactions SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE lipid mediators; therapeutics; metabolomics; chemical gradients; chemotaxis ID LIPID MEDIATORS; NEUTROPHIL MIGRATION; CUTTING EDGE; LIPOXIN A(4); INFLAMMATION; RESOLUTION; MONOCYTES; ATHEROSCLEROSIS; CHEMOTAXIS; GRADIENTS AB Leukocyte trafficking plays a critical role in determining the progress and resolution of inflammation. Although significant progress has been made in understanding the role of leukocyte activation in inflammation, dissecting the interactions between different leukocyte subpopulations during trafficking is hampered by the complexity of in vivo conditions and the lack of detail of current in vitro assays. To measure the effects of the interactions between neutrophils and monocytes migrating in response to various chemoattractants, at single-cell resolution, we developed a microfluidic platform that replicates critical features of focal inflammation sites. We integrated an elastase assay into the focal chemotactic chambers (FCCs) of our device that enabled us to distinguish between phlogistic and nonphlogistic cell recruitment. We found that lipoxin A(4) and resolvin D1, in solution or incorporated into nano-proresolving medicines, reduced neutrophil and monocyte trafficking toward leukotriene B-4. Lipoxin A(4) also reduced the elastase release from homogenous and heterogenous mixtures of neutrophils and monocytes. Surprisingly, the effect of resolvin D1 on heterogenous mixtures was antisynergistic, resulting in a transient spike in elastase activity, which was quickly terminated, and the degraded elastin removed by the leukocytes inside the FCCs. Therefore, the microfluidic assay provides a robust platform for measuring the effect of leukocyte interactions during trafficking and for characterizing the effects of inflammation mediators. C1 [Jones, Caroline N.; Dimisko, Laurie; Wong, Elisabeth; Irimia, Daniel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Shriners Hosp Children, Boston, MA 02114 USA. [Dalli, Jesmond; Serhan, Charles N.] Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Med, Harvard Inst Med, Boston, MA 02115 USA. [Dalli, Jesmond; Serhan, Charles N.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Irimia, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Shriners Hosp Children, Boston, MA 02114 USA. EM dirimia@hms.harvard.edu OI Irimia, Daniel/0000-0001-7347-2082 FU National Institutes of Health [DE19938, GM038765] FX This work was supported, in part, by National Institutes of Health Grants DE19938 (to C.N.S. and D.I.) and GM038765 (to C.N.S.). NR 32 TC 28 Z9 28 U1 1 U2 24 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 11 PY 2012 VL 109 IS 50 BP 20560 EP 20565 DI 10.1073/pnas.1210269109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 058AF UT WOS:000312605600086 PM 23185003 ER PT J AU Tu, DQ Graziano, BR Park, E Zheng, W Li, YQ Goode, BL Eck, MJ AF Tu, Daqi Graziano, Brian R. Park, Eunyoung Zheng, Wei Li, Yiqun Goode, Bruce L. Eck, Michael J. TI Structure of the formin-interaction domain of the actin nucleation-promoting factor Bud6 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ARP2/3 COMPLEX; FILAMENT NUCLEATION; MICROTUBULE ORGANIZATION; ELONGATION-FACTORS; HOMOLOGY-2 DOMAIN; C-TERMINUS; PROTEIN; MECHANISM; YEAST; WASP AB Formin proteins and their associated factors cooperate to assemble unbranched actin filaments in diverse cellular structures. The Saccharomyces cerevisiae formin Bni1 and its associated nucleation-promoting factor (NPF) Bud6 generate actin cables and mediate polarized cell growth. Bud6 binds to both the tail of the formin and G-actin, thereby recruiting monomeric actin to the formin to create a nucleation seed. Here, we structurally and functionally dissect the nucleation-promoting C-terminal region of Bud6 into a Bni1-binding "core" domain and a G-actin binding "flank" domain. The similar to 2-angstrom resolution crystal structure of the Bud6 core domain reveals an elongated dimeric rod with a unique fold resembling a triple-helical coiled-coil. Binding and actin-assembly assays show that conserved residues on the surface of this domain mediate binding to Bni1 and are required for NPF activity. We find that the Bni1 dimer binds two Bud6 dimers and that the Bud6 flank binds a single G-actin molecule. These findings suggest a model in which a Bni1/Bud6 complex with a 2:4 subunit stoichiometry assembles a nucleation seed with Bud6 coordinating up to four actin subunits. C1 [Graziano, Brian R.; Goode, Bruce L.] Brandeis Univ, Dept Biol, Waltham, MA 02454 USA. [Tu, Daqi; Park, Eunyoung; Zheng, Wei; Eck, Michael J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Tu, Daqi; Park, Eunyoung; Zheng, Wei; Li, Yiqun; Eck, Michael J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Graziano, Brian R.; Goode, Bruce L.] Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Waltham, MA 02454 USA. RP Goode, BL (reprint author), Brandeis Univ, Dept Biol, Waltham, MA 02454 USA. EM goode@brandeis.edu; eck@red.dfci.harvard.edu OI Graziano, Brian/0000-0003-1081-908X FU National Institutes of Health (NIH) [GM071834, GM083137]; National Center for Research Resources at the NIH [RR-15301] FX We thank the beamline staff at the Northeastern Collaborative Access Team at the Advanced Photon Source, Argonne National Laboratory, for assistance with data collection. This work was supported, in part, by National Institutes of Health (NIH) Grants GM071834 (to M.J.E.) and GM083137 (to B.L.G.). The Northeastern Collaborative Access Team beamlines are supported by Award RR-15301 from the National Center for Research Resources at the NIH. NR 63 TC 13 Z9 13 U1 1 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 11 PY 2012 VL 109 IS 50 BP E3424 EP E3433 DI 10.1073/pnas.1203035109 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 058AF UT WOS:000312605600010 PM 23161908 ER PT J AU Lin, XM Cook, TJ Zabetian, CP Leverenz, JB Peskind, ER Hu, SC Cain, KC Pan, C Edgar, JS Goodlett, DR Racette, BA Checkoway, H Montine, TJ Shi, M Zhang, J AF Lin, Xiangmin Cook, Travis J. Zabetian, Cyrus P. Leverenz, James B. Peskind, Elaine R. Hu, Shu-Ching Cain, Kevin C. Pan, Catherine Edgar, John Scott Goodlett, David R. Racette, Brad A. Checkoway, Harvey Montine, Thomas J. Shi, Min Zhang, Jing TI DJ-1 isoforms in whole blood as potential biomarkers of Parkinson disease SO SCIENTIFIC REPORTS LA English DT Article ID 2-DIMENSIONAL ELECTROPHORESIS PATTERN; ALPHA-SYNUCLEIN; PROTEIN DJ-1; ALZHEIMERS-DISEASE; PROTEOMIC ANALYSIS; OXIDIZED DJ-1; CELL-DEATH; LEWY BODY; DIAGNOSIS; PHOSPHORYLATION AB DJ-1 is a multifunctional protein that plays an important role in oxidative stress, cell death, and synucleinopathies, including Parkinson disease. Previous studies have demonstrated that total DJ-1 levels decrease in the cerebrospinal fluid, but do not change significantly in human plasma from patients with Parkinson disease when compared with controls. In this study, we measured total DJ-1 and its isoforms in whole blood of patients with Parkinson disease at various stages, Alzheimer disease, and healthy controls to identify potential peripheral biomarkers of PD. In an initial discovery study of 119 subjects, 7 DJ-1 isoforms were reliably detected, and blood levels of those with 4-hydroxy-2-nonenal modifications were discovered to be altered in late-stage Parkinson disease. This result was further confirmed in a validation study of another 114 participants, suggesting that, unlike total DJ-1 levels, post-translationally modified isoforms of DJ-1 from whole blood are candidate biomarkers of late-stage Parkinson disease. C1 [Lin, Xiangmin; Pan, Catherine; Montine, Thomas J.; Shi, Min; Zhang, Jing] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. [Lin, Xiangmin] Fujian Agr & Forestry Univ, Sch Life Sci, Fuzhou 35002, Peoples R China. [Cook, Travis J.; Checkoway, Harvey] Univ Washington, Sch Publ Hlth, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. [Zabetian, Cyrus P.; Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA. [Zabetian, Cyrus P.; Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Zabetian, Cyrus P.; Leverenz, James B.; Hu, Shu-Ching] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Leverenz, James B.; Peskind, Elaine R.] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [Peskind, Elaine R.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Cain, Kevin C.] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. [Edgar, John Scott; Goodlett, David R.] Univ Washington, Sch Pharm, Dept Med Chem, Seattle, WA 98195 USA. [Racette, Brad A.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. RP Zhang, J (reprint author), Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. EM zhangj@uw.edu RI Shi, Min/G-6165-2012; OI Shi, Min/0000-0002-6901-2558; , xiangmin/0000-0001-9128-689X; Zabetian, Cyrus/0000-0002-7739-4306; Lin, Xiangmin/0000-0003-2216-0198 FU National Institutes of Health [NS057567, NS065070, P50NS062684, NS060252, AG025327, AG033398, ES004696, ES016873, ES019277, P30ES007033, ES015459-02]; Department of Veterans Affairs [1I01BX000531]; Shaw endowment FX The authors deeply appreciate all participants' donation of time and blood for making our study possible. We would also like to thank John D. Chapman for providing technical expertise and assistance in LTQ-Orbitrap MS proteomic processing of our samples. This work was supported by the National Institutes of Health [grant numbers NS057567, NS065070, P50NS062684, NS060252, AG025327, AG033398, ES004696, ES016873, ES019277, P30ES007033, ES015459-02]; Department of Veterans Affairs [grant number 1I01BX000531]; and Shaw endowment. NR 42 TC 27 Z9 29 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD DEC 11 PY 2012 VL 2 AR 954 DI 10.1038/srep00954 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 053MD UT WOS:000312274900003 PM 23233873 ER PT J AU Fontan, L Yang, CH Kabaleeswaran, V Volpon, L Osborne, MJ Beltran, E Garcia, M Cerchietti, L Shaknovich, R Yang, SN Fang, F Gascoyne, RD Martinez-Climent, JA Glickman, JF Borden, K Wu, H Melnick, A AF Fontan, Lorena Yang, Chenghua Kabaleeswaran, Venkataraman Volpon, Laurent Osborne, Michael J. Beltran, Elena Garcia, Monica Cerchietti, Leandro Shaknovich, Rita Yang, Shao Ning Fang, Fang Gascoyne, Randy D. Angel Martinez-Climent, Jose Glickman, J. Fraser Borden, Katherine Wu, Hao Melnick, Ari TI MALT1 Small Molecule Inhibitors Specifically Suppress ABC-DLBCL In Vitro and In Vivo SO CANCER CELL LA English DT Article ID B-CELL LYMPHOMA; NF-KAPPA-B; KINASE-C INHIBITOR; T-CELL; CHROMOSOMAL TRANSLOCATION; PARACASPASE MALT1; CRYSTAL-STRUCTURE; PROTEASE ACTIVITY; HODGKIN-LYMPHOMA; TISSUE LYMPHOMA AB MALT1 cleavage activity is linked to the pathogenesis of activated B cell-like diffuse large B cell lymphoma (ABC-DLBCL), a chemoresistant form of DLBCL. We developed a MALT1 activity assay and identified chemically diverse MALT1 inhibitors. A selected lead compound, MI-2, featured direct binding to MALT1 and suppression of its protease function. MI-2 concentrated within human ABC-DLBCL cells and irreversibly inhibited cleavage of MALT1 substrates. This was accompanied by NE-kappa B reporter activity suppression, c-REL nuclear localization inhibition, and NF-kappa B target gene downregulation. Most notably, MI-2 was nontoxic to mice, and displayed selective activity against ABC-DLBCL cell lines in vitro and xenotransplanted ABC-DLBCL tumors in vivo. The compound was also effective against primary human non-germinal center B cell-like DLBCLs ex vivo. C1 [Yang, Chenghua; Kabaleeswaran, Venkataraman; Wu, Hao] Weill Cornell Med Coll, Dept Biochem, New York, NY 10021 USA. [Fontan, Lorena; Garcia, Monica; Cerchietti, Leandro; Shaknovich, Rita; Yang, Shao Ning; Fang, Fang; Melnick, Ari] Weill Cornell Med Coll, Div Hematol & Med Oncol, New York, NY 10021 USA. [Fontan, Lorena; Garcia, Monica; Fang, Fang; Melnick, Ari] Weill Cornell Med Coll, Dept Pharmacol, New York, NY 10021 USA. [Shaknovich, Rita] Weill Cornell Med Coll, Dept Pathol, Div Immunopathol, New York, NY 10021 USA. [Fontan, Lorena; Beltran, Elena; Angel Martinez-Climent, Jose] Univ Navarra, Ctr Appl Med Res, Div Oncol, Navarra 31008, Spain. [Kabaleeswaran, Venkataraman; Wu, Hao] Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA. [Kabaleeswaran, Venkataraman; Wu, Hao] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Volpon, Laurent; Osborne, Michael J.; Borden, Katherine] Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada. [Gascoyne, Randy D.] BC Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 1L3, Canada. [Glickman, J. Fraser] Rockefeller Univ, High Throughput Screening Resource Ctr, New York, NY 10065 USA. RP Wu, H (reprint author), Weill Cornell Med Coll, Dept Biochem, New York, NY 10021 USA. EM hao.wu@childrens.harvard.edu; amm2014@med.cornell.edu RI Glickman, Joseph/H-3021-2013; Beltran, Elena/K-8785-2014; Martinez-Climent, Jose/I-9199-2012; OI Glickman, Joseph/0000-0002-6706-4039; Martinez-Climent, Jose/0000-0002-7938-3950; Cerchietti, Leandro/0000-0003-0608-1350 FU Spanish Ministry of Science Fellowship "Sara Borrell"; Irvington Institute Postdoctoral Fellowship Program of the Cancer Research Institute; Leukemia and Lymphoma Society Translational Research Program [6210-12]; Chemotherapy Foundation; Beverly and Raymond Sackler Center for Physical and Biomedical Sciences FX We thank Paulus Erbel, Martin Renatus, and Nicola Hughes (Novartis Institutes for BioMedical Research, Basel, Switzerland) for mass spectrometry, NMR experiments, and advice; Beatriz Bellosillo (H. del Mar, Barcelona, Spain) and Miguel A. Pins (Hospital Marques de Valdecillas, Santander, Spain) for providing lymphoma samples; and Ermelinda Damko, Liwei Wang, Qi Qiao, and Jennifer Ishii for technical assistance. L.F. is supported by the Spanish Ministry of Science Fellowship "Sara Borrell." C.Y. was supported by the Irvington Institute Postdoctoral Fellowship Program of the Cancer Research Institute. H.W. and A.M. are supported by Leukemia and Lymphoma Society Translational Research Program 6210-12. A.M. is a Burroughs Wellcome Clinical Translational Scientist and is supported by the Chemotherapy Foundation and the Beverly and Raymond Sackler Center for Physical and Biomedical Sciences. NR 47 TC 68 Z9 68 U1 2 U2 26 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD DEC 11 PY 2012 VL 22 IS 6 BP 812 EP 824 DI 10.1016/j.ccr.2012.11.003 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 056CW UT WOS:000312467000012 PM 23238016 ER PT J AU Rienstra, M Lubitz, SA Mahida, S Sinner, MF Ellinor, PT Van Gelder, IC Magnani, JW Fontes, JD Benjamin, EJ AF Rienstra, Michiel Lubitz, Steven A. Mahida, Saagar Sinner, Moritz F. Ellinor, Patrick T. Van Gelder, Isabelle C. Magnani, Jared W. Fontes, Joao D. Benjamin, Emelia J. TI Response to Letter Regarding Article, "Symptoms and Functional Status of Patients With Atrial Fibrillation: State of the Art and Future Research Opportunities" SO CIRCULATION LA English DT Letter ID VENTRICULAR DIASTOLIC DYSFUNCTION C1 [Rienstra, Michiel; Lubitz, Steven A.; Mahida, Saagar; Sinner, Moritz F.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. [Van Gelder, Isabelle C.] Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Groningen, Netherlands. [Magnani, Jared W.; Fontes, Joao D.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA. [Magnani, Jared W.; Fontes, Joao D.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA. RP Rienstra, M (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. OI Benjamin, Emelia/0000-0003-4076-2336; Rienstra, Michiel/0000-0002-2581-070X NR 5 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 11 PY 2012 VL 126 IS 24 BP E350 EP E350 DI 10.1161/CIRCULATIONAHA.112.145185 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 053MK UT WOS:000312275600004 ER PT J AU Li, ZZ Gilbert, JA Zhang, YY Zhang, MS Qiu, Q Ramanujan, K Shavlakadze, T Eash, JK Scaramozza, A Goddeeris, MM Kirsch, DG Campbell, KP Brack, AS Glass, DJ AF Li, Zhizhong Gilbert, Jason A. Zhang, Yunyu Zhang, Minsi Qiu, Qiong Ramanujan, Krishnan Shavlakadze, Tea Eash, John K. Scaramozza, Annarita Goddeeris, Matthew M. Kirsch, David G. Campbell, Kevin P. Brack, Andrew S. Glass, David J. TI An HMGA2-IGF2BP2 Axis Regulates Myoblast Proliferation and Myogenesis SO DEVELOPMENTAL CELL LA English DT Article ID MUSCLE SATELLITE CELLS; MUSCULAR-DYSTROPHY MDX; GROWTH-FACTOR RECEPTOR; GROUP PROTEIN HMGA2; IN-VIVO MODULATION; SKELETAL-MUSCLE; SELF-RENEWAL; PROGENITOR CELLS; STEM-CELLS; DIFFERENTIATION AB A group of genes that are highly and specifically expressed in proliferating skeletal myoblasts during myogenesis was identified. Expression of one of these genes, Hmga2, increases coincident with satellite cell activation, and later its expression significantly declines correlating with fusion of myoblasts into myotubes. Hmga2 knockout mice exhibit impaired muscle development and reduced myoblast proliferation, while overexpression of HMGA2 promotes myoblast growth. This perturbation in proliferation can be explained by the finding that HMGA2 directly regulates the RNA-binding protein IGF2BP2. Add-back of IGF2BP2 rescues the phenotype. IGF2BP2 in turn binds to and controls the translation of a set of mRNAs, including c-myc, Sp1, and lgf1r. These data demonstrate that the HMGA2-IGF2BP2 axis functions as a key regulator of satellite cell activation and therefore skeletal muscle development. C1 [Li, Zhizhong; Gilbert, Jason A.; Zhang, Yunyu; Ramanujan, Krishnan; Shavlakadze, Tea; Eash, John K.; Glass, David J.] Novartis Inst Biomed Res, Cambridge, MA 02139 USA. [Zhang, Minsi; Kirsch, David G.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. [Qiu, Qiong; Kirsch, David G.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA. [Scaramozza, Annarita; Brack, Andrew S.] Harvard Univ, Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Scaramozza, Annarita; Brack, Andrew S.] Harvard Univ, Harvard Stem Cell Inst, Boston, MA 02114 USA. [Goddeeris, Matthew M.; Campbell, Kevin P.] Univ Iowa, Roy J & Lucille A Carver Coll Med, Senator Paul D Wellstone Muscular Dystrophy Coope, Howard Hughes Med Inst,Dept Neurol,Dept Mol Physi, Iowa City, IA 52242 USA. [Goddeeris, Matthew M.; Campbell, Kevin P.] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Internal Med, Iowa City, IA 52242 USA. RP Glass, DJ (reprint author), Novartis Inst Biomed Res, Cambridge, MA 02139 USA. EM david.glass@novartis.com FU Novartis Institutes for Biomedical Research; [R01 CA138265]; [U54 NS053672] FX We thank Mark Fishman and Brian Richardson for their support and David Sabatini, Carson Thoreen, Amy Titelbaum, John Halupowski, Laura Le, and Robin Ge for excellent advice and assistance. Thanks to Chen-Ming Fan for the kind gift of the Pax7 antibody. Z.L is supported by the Presidential Postdoctoral Fellow program at the Novartis Institutes for Biomedical Research. This work was supported in part by R01 CA138265 (to D.G.K.) and in part by U54 NS053672 (to K.P.C.). K.P.C. is an investigator of the Howard Hughes Medical Institute. NR 40 TC 41 Z9 42 U1 2 U2 20 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD DEC 11 PY 2012 VL 23 IS 6 BP 1176 EP 1188 DI 10.1016/j.devcel.2012.10.019 PG 13 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 055PP UT WOS:000312429200014 PM 23177649 ER PT J AU Wang, GY Zhang, JW Liu, LY Sharma, S Dong, QH AF Wang, Guanyu Zhang, Jiawei Liu, Luying Sharma, Sherven Dong, Qinghua TI Quercetin Potentiates Doxorubicin Mediated Antitumor Effects against Liver Cancer through p53/Bcl-xl SO PLOS ONE LA English DT Article ID INDUCED APOPTOSIS; P-GLYCOPROTEIN; IN-VITRO; HEPATOCELLULAR-CARCINOMA; INDUCED CARDIOTOXICITY; CELL LINES; RAT-LIVER; EXPRESSION; FLAVONOIDS; P53 AB Background: The dose-dependent toxicities of doxorubicin (DOX) limit its clinical applications, particularly in drug-resistant cancers, such as liver cancer. In this study, we investigated the role of quercetin on the antitumor effects of DOX on liver cancer cells and its ability to provide protection against DOX-mediated liver damage in mice. Methodology and Results: The MTT and Annexin V/PI staining assay demonstrated that quercetin selectively sensitized DOX-induced cytotoxicity against liver cancer cells while protecting normal liver cells. The increase in DOX-mediated apoptosis in hepatoma cells by quercetin was p53-dependent and occurred by downregulating Bcl-xl expression. Z-VAD-fmk (caspase inhibitor), pifithrin-alpha (p53 inhibitor), or overexpressed Bcl-xl decreased the effects of quercetin on DOX-mediated apoptosis. The combined treatment of quercetin and DOX significantly reduced the growth of liver cancer xenografts in mice. Moreover, quercetin decreased the serum levels of alanine aminotransferase and aspartate aminotransferase that were increased in DOX-treated mice. Quercetin also reversed the DOX-induced pathological changes in mice livers. Conclusion and Significance: These results indicate that quercetin potentiated the antitumor effects of DOX on liver cancer cells while protecting normal liver cells. Therefore, the development of quercetin may be beneficial in a combined treatment with DOX for increased therapeutic efficacy against liver cancer. C1 [Dong, Qinghua] Zhejiang Univ, Sch Med, Biomed Res Ctr, Sir Run Run Shaw Hosp, Hangzhou 310003, Zhejiang, Peoples R China. [Wang, Guanyu] Zhejiang Univ, Sch Med, Dept Gen Surg, Sir Run Run Shaw Hosp, Hangzhou 310003, Zhejiang, Peoples R China. [Zhang, Jiawei] Zhejiang Univ, Inst Canc, Affiliated Hosp 2, Hangzhou 310003, Zhejiang, Peoples R China. [Liu, Luying] Zhejiang Canc Hosp, Dept Radiotherapy, Hangzhou, Zhejiang, Peoples R China. [Sharma, Sherven] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Sharma, Sherven] W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. [Dong, Qinghua] China Natl Minist Educ, Key Lab Canc Prevent & Intervent, Key Lab Canc Biotherapy Zhejiang Prov, Hangzhou, Zhejiang, Peoples R China. RP Dong, QH (reprint author), Zhejiang Univ, Sch Med, Biomed Res Ctr, Sir Run Run Shaw Hosp, Hangzhou 310003, Zhejiang, Peoples R China. EM dongqinghua@zju.edu.cn FU National Natural Science Foundation of China [30400521]; Science Technology Department of Zhejiang Province [2012R10047, 2012C33116]; Education Department of Zhejiang Province [Y201224108] FX This work was supported by the National Natural Science Foundation of China (No.: 30400521), the Science Technology Department of Zhejiang Province (No.: 2012R10047 to QD and No.: 2012C33116 to GW) and the Education Department of Zhejiang Province (No.: Y201224108). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 12 Z9 13 U1 0 U2 40 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 11 PY 2012 VL 7 IS 12 AR e51764 DI 10.1371/journal.pone.0051764 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 053RN UT WOS:000312290800097 PM 23240061 ER PT J AU Tsao, CW Preis, SR Peloso, GM Hwang, SJ Kathiresan, S Fox, CS Cupples, LA Hoffmann, U O'Donnell, CJ AF Tsao, Connie W. Preis, Sarah Rosner Peloso, Gina M. Hwang, Shih-Jen Kathiresan, Sekar Fox, Caroline S. Cupples, L. Adrienne Hoffmann, Udo O'Donnell, Christopher J. TI Relations of Long-Term and Contemporary Lipid Levels and Lipid Genetic Risk Scores With Coronary Artery Calcium in the Framingham Heart Study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE coronary artery calcium; genetic risk score; lipids ID GENOME-WIDE ASSOCIATION; LOW-DENSITY-LIPOPROTEIN; CARDIOVASCULAR RISK; COMPUTED-TOMOGRAPHY; YOUNG-ADULTS; DISEASE; CALCIFICATION; ATHEROSCLEROSIS; PREDICTION; LOCI AB Objectives This study evaluated the association of timing of lipid levels and lipid genetic risk score (GRS) with subclinical atherosclerosis. Background Atherosclerosis is a slowly progressive disorder influenced by suboptimal lipid levels. Long-term versus contemporary lipid levels may more strongly impact the development of coronary artery calcium (CAC). Methods Framingham Heart Study (FHS) Offspring Cohort participants (n = 1,156, 44% male, 63 +/- 9 years) underwent serial fasting lipids (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein, and triglycerides), Exam 1 (1971 to 1975) to Exam 7 (1998 to 2001). FHS Third Generation Cohort participants (n = 1,954, 55% male, 45 +/- 6 years) had fasting lipid profiles assessed, 2002 to 2005. Computed tomography (2002 to 2005) measured CAC. Lipid GRSs were computed from significantly associated single-nucleotide polymorphisms. The association between early, long-term average, and contemporary lipids, and lipid GRS with elevated CAC was assessed using logistic regression. Results In FHS Offspring, Exam 1 and long-term average as compared with Exam 7 lipid measurements, including untreated lipid levels, were strongly associated with elevated CAC. In the FHS Third Generation, contemporary lipids were associated with CAC. The LDL-C GRS was associated with CAC (age-/sex-adjusted odds ratio: 1.14, 95% confidence interval: 1.00 to 1.29, p = 0.04). However, addition of the GRS to the lipid models did not result in a significant increase in the odds ratio or C-statistic for any lipid measure. Conclusions Early and long-term average lipid levels, as compared with contemporary measures, are more strongly associated with elevated CAC. Lipid GRS was associated with lipid levels but did not predict elevated CAC. Adult early and long-term average lipid levels provide important information when assessing subclinical atherosclerosis and cardiovascular risk. (J Am Coll Cardiol 2012;60:2364-71) (C) 2012 by the American College of Cardiology Foundation C1 [Tsao, Connie W.; Preis, Sarah Rosner; Peloso, Gina M.; Hwang, Shih-Jen; Fox, Caroline S.; Cupples, L. Adrienne; O'Donnell, Christopher J.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [Tsao, Connie W.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Cardiovasc, Dept Med,Sch Med, Boston, MA 02215 USA. [Preis, Sarah Rosner; Peloso, Gina M.; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Kathiresan, Sekar; O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA USA. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Div Endocrinol & Metab, Sch Med, Boston, MA 02115 USA. [Hoffmann, Udo] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Tsao, CW (reprint author), Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. OI Preis, Sarah/0000-0002-9360-4166; Cupples, L. Adrienne/0000-0003-0273-7965 FU National Heart, Lung, and Blood Institute [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; ACCF; Merck; Pfizer FX The Framingham Heart Study (FHS) is supported by the National Heart, Lung, and Blood Institute (contract N01-HC-25195). This work was partially supported by the National Heart, Lung, and Blood Institute's contract with Affymetrix, Inc, for genotyping services (contract N02-HL-6-4278). Analyses are partially based on resources from Framingham Heart Study investigators in the SNP Health Association Resource project. Dr. Tsao is partially supported by an award from the ACCF. Dr. Kathiresan is a member of the Scientific Advisory Board for Merck; and has received research grants from Merck and Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Tsao and Preis contributed equally to this work. NR 32 TC 8 Z9 8 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 11 PY 2012 VL 60 IS 23 BP 2364 EP 2371 DI 10.1016/j.jacc.2012.09.007 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 048ZS UT WOS:000311952400004 PM 23141485 ER PT J AU Gaziano, JM AF Gaziano, J. Michael TI Should We Fast Before We Measure Our Lipids? SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material ID NONFASTING TRIGLYCERIDES; HEART-DISEASE; WOMEN; RISK C1 [Gaziano, J. Michael] Brigham & Womens Hosp, Div Aging, Dept Med, VA Boston Healthcare Syst, Boston, MA 02120 USA. [Gaziano, J. Michael] Harvard Univ, Sch Med, Boston, MA USA. RP Gaziano, JM (reprint author), Brigham & Womens Hosp, Div Aging, Dept Med, VA Boston Healthcare Syst, 1620 Tremont St, Boston, MA 02120 USA. EM jmgaziano@partners.org NR 8 TC 12 Z9 12 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD DEC 10 PY 2012 VL 172 IS 22 BP 1705 EP 1706 DI 10.1001/jamainternmed.2013.1771 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 052LE UT WOS:000312198300002 PM 23401886 ER PT J AU Kangovi, S Long, JA Emanuel, E AF Kangovi, Shreya Long, Judith A. Emanuel, Ezekiel TI Community Health Workers Combat Readmission SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material ID GENERAL MEDICINE PATIENTS C1 [Kangovi, Shreya; Long, Judith A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Kangovi, Shreya; Long, Judith A.] Univ Penn, Div Gen Internal Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Emanuel, Ezekiel] Univ Penn, Dept Med Eth & Hlth Policy, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kangovi, Shreya; Long, Judith A.] Univ Penn, Robert Wood Johnson Clin Scholars Program, Philadelphia, PA 19104 USA. [Emanuel, Ezekiel] Univ Penn, Off Provost, Philadelphia, PA 19104 USA. [Emanuel, Ezekiel] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. RP Kangovi, S (reprint author), 423 Guardian Dr,Blockley Hall,13th Floor, Philadelphia, PA 19104 USA. EM kangovi@mail.med.upenn.edu NR 12 TC 12 Z9 12 U1 2 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD DEC 10 PY 2012 VL 172 IS 22 BP 1756 EP 1757 DI 10.1001/2013.jamainternmed.82 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 052LE UT WOS:000312198300015 PM 23128914 ER PT J AU Ganem, NJ Pellman, D AF Ganem, Neil J. Pellman, David TI Linking abnormal mitosis to the acquisition of DNA damage SO JOURNAL OF CELL BIOLOGY LA English DT Review ID MEROTELIC KINETOCHORE ORIENTATION; MAMMALIAN TISSUE-CELLS; PREMATURELY CONDENSED CHROMOSOMES; SPINDLE-ASSEMBLY CHECKPOINT; DOUBLE-STRAND BREAKS; MITOTIC ARREST; CANCER-CELLS; EXTRA CENTROSOMES; ANAPHASE BRIDGES; ULTRASTRUCTURAL ORGANIZATION AB Cellular defects that impair the fidelity of mitosis promote chromosome missegregation and aneuploidy. Increasing evidence reveals that errors in mitosis can also promote the direct and indirect acquisition of DNA damage and chromosome breaks. Consequently, deregulated cell division can devastate the integrity of the normal genome and unleash a variety of oncogenic stimuli that may promote transformation. Recent work has shed light on the mechanisms that link abnormal mitosis with the development of DNA damage, how cells respond to such affronts, and the potential impact on tumorigenesis. C1 [Ganem, Neil J.; Pellman, David] Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Cell Biol, Howard Hughes Med Inst,Dept Pediat Oncol,Children, Boston, MA 02115 USA. RP Ganem, NJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Cell Biol, Howard Hughes Med Inst,Dept Pediat Oncol,Children, 44 Binney St, Boston, MA 02115 USA. EM neil_ganem@dfci.harvard.edu FU National Cancer Institute [K99CA154531-01]; Howard Hughes Medical Institute; National Institutes of Health FX N. Ganem is supported by a K99 award (K99CA154531-01) from the National Cancer Institute. D. Pellman is supported by the Howard Hughes Medical Institute and awards from the National Institutes of Health. NR 139 TC 72 Z9 73 U1 1 U2 46 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 10 PY 2012 VL 199 IS 6 BP 871 EP 881 DI 10.1083/jcb.201210040 PG 11 WC Cell Biology SC Cell Biology GA 053DP UT WOS:000312251000003 PM 23229895 ER PT J AU Chin, JY Hong, TS Ryan, DP AF Chin, Joanna Y. Hong, Theodore S. Ryan, David P. TI Mitomycin in Anal Cancer: Still the Standard of Care SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; RADIATION-THERAPY; RANDOMIZED-TRIAL; PHASE-II; RADIOTHERAPY; CHEMOTHERAPY; 5-FLUOROURACIL; FLUOROURACIL; CISPLATIN AB A 52-year-old woman presents with a 2-month history of bright red blood per rectum. Her bleeding is associated with bowel movements and a sense of incomplete evacuation. She denies fecal incontinence or change in stool caliber. On digital rectal examination, the tumor is palpated approximately 3 cm from the anal verge, posterior and slightly to the right, positioned at the top of the anal canal and extending into the rectum, measuring approximately 2.5 cm. Additionally, a firm 1.5-cm left-sided inguinal node is palpated. The patient is then referred for colonoscopy, which reveals a mass in the anal canal; biopsy of the mass shows squamous cell carcinoma. Positron emission tomography-computed tomography (PET-CT) demonstrates thickening in the low rectum with [F-18] fluorodeoxyglucose (FDG) avidity (Figs 1A, 1B). The left inguinal node is visualized, as is a perirectal lymph node with associated FDG avidity (Figs 1C, 1D). The patient is staged as having T2N3 squamous cell carcinoma of the anal canal (Table 1). Her medical history is otherwise unremarkable, including for HIV, prior abnormal Papanicolaou smears, and other risk factors for human papillomavirus (HPV) exposure. C1 [Chin, Joanna Y.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Chin, JY (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 14 TC 4 Z9 4 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 10 PY 2012 VL 30 IS 35 BP 4297 EP 4301 DI 10.1200/JCO.2012.44.8878 PG 5 WC Oncology SC Oncology GA 052KG UT WOS:000312195900009 PM 23150704 ER PT J AU Weischer, M Nordestgaard, BG Pharoah, P Bolla, MK Nevanlinna, H van't Veer, LJ Garcia-Closas, M Hopper, JL Hall, P Andrulis, IL Devilee, P Fasching, PA Anton-Culver, H Lambrechts, D Hooning, M Cox, A Giles, GG Burwinkel, B Lindblom, A Couch, FJ Mannermaa, A Alnaes, GG John, EM Dork, T Flyger, H Dunning, AM Wang, Q Muranen, TA van Hien, R Figueroa, J Southey, MC Czene, K Knight, JA Tollenaar, RAEM Beckmann, MW Ziogas, A Christiaens, MR Collee, JM Reed, MWR Severi, G Marme, F Margolin, S Olson, JE Kosma, VM Kristensen, VN Miron, A Bogdanova, N Shah, M Blomqvist, C Broeks, A Sherman, M Phillips, KA Li, JM Liu, JJ Glendon, G Seynaeve, C Ekici, AB Leunen, K Kriege, M Cross, SS Baglietto, L Sohn, C Wang, XS Kataja, V Borresen-Dale, AL Meyer, A Easton, DF Schmidt, MK Bojesen, SE AF Weischer, Maren Nordestgaard, Borge G. Pharoah, Paul Bolla, Manjeet K. Nevanlinna, Heli van't Veer, Laura J. Garcia-Closas, Montserrat Hopper, John L. Hall, Per Andrulis, Irene L. Devilee, Peter Fasching, Peter A. Anton-Culver, Hoda Lambrechts, Diether Hooning, Maartje Cox, Angela Giles, Graham G. Burwinkel, Barbara Lindblom, Annika Couch, Fergus J. Mannermaa, Arto Alnaes, Grethe Grenaker John, Esther M. Doerk, Thilo Flyger, Henrik Dunning, Alison M. Wang, Qin Muranen, Taru A. van Hien, Richard Figueroa, Jonine Southey, Melissa C. Czene, Kamila Knight, Julia A. Tollenaar, Rob A. E. M. Beckmann, Matthias W. Ziogas, Argyrios Christiaens, Marie-Rose Collee, Johanna Margriet Reed, Malcolm W. R. Severi, Gianluca Marme, Frederik Margolin, Sara Olson, Janet E. Kosma, Veli-Matti Kristensen, Vessela N. Miron, Alexander Bogdanova, Natalia Shah, Mitul Blomqvist, Carl Broeks, Annegien Sherman, Mark Phillips, Kelly-Anne Li, Jingmei Liu, Jianjun Glendon, Gord Seynaeve, Caroline Ekici, Arif B. Leunen, Karin Kriege, Mieke Cross, Simon S. Baglietto, Laura Sohn, Christof Wang, Xianshu Kataja, Vesa Borresen-Dale, Anne-Lise Meyer, Andreas Easton, Douglas F. Schmidt, Marjanka K. Bojesen, Stig E. TI CHEK2*1100delC Heterozygosity in Women With Breast Cancer Associated With Early Death, Breast Cancer-Specific Death, and Increased Risk of a Second Breast Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TUMOR CHARACTERISTICS; MENDELIAN RANDOMIZATION; GERMLINE MUTATION; CHEK2; SUSCEPTIBILITY; PROGNOSIS; SURVIVAL; VARIANT; GENE AB Purpose We tested the hypotheses that CHEK2*1100delC heterozygosity is associated with increased risk of early death, breast cancer-specific death, and risk of a second breast cancer in women with a first breast cancer. Patients and Methods From 22 studies participating in the Breast Cancer Association Consortium, 25,571 white women with invasive breast cancer were genotyped for CHEK2*1100delC and observed for up to 20 years (median, 6.6 years). We examined risk of early death and breast cancer-specific death by estrogen receptor status and risk of a second breast cancer after a first breast cancer in prospective studies. Results CHEK2*1100delC heterozygosity was found in 459 patients (1.8%). In women with estrogen receptor-positive breast cancer, multifactorially adjusted hazard ratios for heterozygotes versus noncarriers were 1.43 (95% CI, 1.12 to 1.82; log-rank P = .004) for early death and 1.63 (95% CI, 1.24 to 2.15; log-rank P < .001) for breast cancer-specific death. In all women, hazard ratio for a second breast cancer was 2.77 (95% CI, 2.00 to 3.83; log-rank P < .001) increasing to 3.52 (95% CI, 2.35 to 5.27; log-rank P < .001) in women with estrogen receptor-positive first breast cancer only. Conclusion Among women with estrogen receptor-positive breast cancer, CHEK2*1100delC heterozygosity was associated with a 1.4-fold risk of early death, a 1.6-fold risk of breast cancer-specific death, and a 3.5-fold risk of a second breast cancer. This is one of the few examples of a genetic factor that influences long-term prognosis being documented in an extensive series of women with breast cancer. J Clin Oncol 30: 4308-4316. (C) 2012 by American Society of Clinical Oncology C1 [Weischer, Maren; Nordestgaard, Borge G.; Flyger, Henrik; Bojesen, Stig E.] Univ Copenhagen, Copenhagen, Denmark. [Pharoah, Paul; Bolla, Manjeet K.; Dunning, Alison M.; Wang, Qin; Shah, Mitul; Easton, Douglas F.] Univ Cambridge, Cambridge, England. [Garcia-Closas, Montserrat] Inst Canc Res, London SW3 6JB, England. [Cox, Angela; Reed, Malcolm W. R.; Cross, Simon S.] Univ Sheffield, Sheffield, S Yorkshire, England. [Nevanlinna, Heli; Muranen, Taru A.; Blomqvist, Carl] Univ Helsinki, Helsinki, Finland. [Nevanlinna, Heli; Muranen, Taru A.; Blomqvist, Carl] Univ Helsinki, Cent Hosp, Helsinki, Finland. [Mannermaa, Arto; Kosma, Veli-Matti; Kataja, Vesa] Univ Eastern Finland, Kuopio, Finland. [Mannermaa, Arto; Kosma, Veli-Matti; Kataja, Vesa] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [van't Veer, Laura J.; van Hien, Richard; Broeks, Annegien; Schmidt, Marjanka K.] Netherlands Canc Inst, Amsterdam, Netherlands. [Devilee, Peter; Tollenaar, Rob A. E. M.] Leiden Univ, Med Ctr, Leiden, Netherlands. [Hooning, Maartje; Collee, Johanna Margriet; Kriege, Mieke] Erasmus Univ, Med Ctr, Rotterdam, Netherlands. [Seynaeve, Caroline] Erasmus MC, Daniel den Hoed Canc Ctr, Rotterdam, Netherlands. [Hopper, John L.; Giles, Graham G.; Southey, Melissa C.; Severi, Gianluca; Baglietto, Laura] Univ Melbourne, Melbourne, Vic, Australia. [Giles, Graham G.; Severi, Gianluca; Baglietto, Laura] Canc Council Victoria, Melbourne, Vic, Australia. [Phillips, Kelly-Anne] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Phillips, Kelly-Anne] Univ Melbourne, Melbourne, Vic, Australia. [Hall, Per; Lindblom, Annika; Czene, Kamila; Margolin, Sara] Karolinska Inst, Stockholm, Sweden. [Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Fasching, Peter A.; Beckmann, Matthias W.; Ekici, Arif B.] Univ Erlangen Nurnberg, D-91054 Erlangen, Germany. [Fasching, Peter A.; Beckmann, Matthias W.] Comprehens Canc Ctr Erlangen Nuremberg, Erlangen, Germany. [Burwinkel, Barbara; Marme, Frederik; Sohn, Christof] Univ Heidelberg, Heidelberg, Germany. [Burwinkel, Barbara] German Canc Res Ctr, D-6900 Heidelberg, Germany. [Doerk, Thilo; Bogdanova, Natalia; Meyer, Andreas] Hannover Med Sch, D-3000 Hannover, Germany. [Fasching, Peter A.] Univ Calif Los Angeles, Los Angeles, CA USA. [Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Irvine, CA USA. [John, Esther M.; Kristensen, Vessela N.] Canc Prevent Inst Calif, Fremont, CA USA. [Lambrechts, Diether] VIB, Vesalius Res Ctr, Louvain, Belgium. [Christiaens, Marie-Rose; Leunen, Karin] Katholieke Univ Leuven, Univ Hosp Leuven, Louvain, Belgium. [Couch, Fergus J.; Olson, Janet E.; Wang, Xianshu] Mayo Clin, Rochester, MN USA. [Alnaes, Grethe Grenaker; Borresen-Dale, Anne-Lise] Univ Oslo, Norwegian Radium Hosp, Oslo Univ Hosp, Oslo, Norway. [Figueroa, Jonine; Sherman, Mark] NCI, Bethesda, MD 20892 USA. [Miron, Alexander] Dana Farber Canc Inst, Boston, MA 02115 USA. [Li, Jingmei; Liu, Jianjun] Genome Inst Singapore, Singapore, Singapore. RP Bojesen, SE (reprint author), Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Herlev Ringvej 75, DK-2730 Herlev, Denmark. EM stig.egil.bojesen@regionh.dk RI Verdrengh, Evelien/H-4571-2012; Li, Jingmei/I-2904-2012; Ekici, Arif/C-3971-2013; Andrulis, Irene/E-7267-2013; Knight, Julia/A-6843-2012; Dork, Thilo/J-8620-2012; Garcia-Closas, Montserrat /F-3871-2015; OI Muranen, Taru/0000-0002-5895-1808; Nevanlinna, Heli/0000-0002-0916-2976; Cox, Angela/0000-0002-5138-1099; Dunning, Alison Margaret/0000-0001-6651-7166; Giles, Graham/0000-0003-4946-9099; Li, Jingmei/0000-0001-8587-7511; Garcia-Closas, Montserrat /0000-0003-1033-2650; Czene, Kamila/0000-0002-3233-5695; Cross, Simon/0000-0003-2044-1754; Phillips, Kelly-Anne/0000-0002-0475-1771 FU Cancer Research UK [10118, 10119, 10124]; NCI NIH HHS [P50 CA116201, R01 CA122340] NR 20 TC 39 Z9 39 U1 0 U2 10 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 10 PY 2012 VL 30 IS 35 BP 4308 EP 4316 DI 10.1200/JCO.2012.42.7336 PG 9 WC Oncology SC Oncology GA 052KG UT WOS:000312195900011 PM 23109706 ER PT J AU Gunderson, LL Winter, KA Ajani, JA Pedersen, JE Moughan, J Benson, AB Thomas, CR Mayer, RJ Haddock, MG Rich, TA Willett, CG AF Gunderson, Leonard L. Winter, Kathryn A. Ajani, Jaffer A. Pedersen, John E. Moughan, Jennifer Benson, Al B., III Thomas, Charles R., Jr. Mayer, Robert J. Haddock, Michael G. Rich, Tyvin A. Willett, Christopher G. TI Long-Term Update of US GI Intergroup RTOG 98-11 Phase III Trial for Anal Carcinoma: Survival, Relapse, and Colostomy Failure With Concurrent Chemoradiation Involving Fluorouracil/Mitomycin Versus Fluorouracil/Cisplatin SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RANDOMIZED-TRIAL; MAMMALIAN-CELLS; LOCAL-CONTROL; MITOMYCIN-C; CANCER; RADIATION; RADIOTHERAPY; CHEMOTHERAPY; THERAPY; 5-FLUOROURACIL AB Purpose On initial publication of GI Intergroup Radiation Therapy Oncology Group (RTOG) 98-11 [A Phase III Randomized Study of 5-Fluorouracil (5-FU), Mitomycin, and Radiotherapy Versus 5-Fluorouracil, Cisplatin and Radiotherapy in Carcinoma of the Anal Canal], concurrent chemoradiation (CCR) with fluorouracil (FU) plus mitomycin (MMC) decreased colostomy failure (CF) when compared with induction plus concurrent FU plus cisplatin (CDDP), but did not significantly impact disease-free survival (DFS) or overall survival (OS) for anal canal carcinoma. The intent of the updated analysis was to determine the long-term impact of treatment on survival (DFS, OS, colostomy-free survival [CFS]), CF, and relapse (locoregional failure [LRF], distant metastasis) in this patient group. Patients and Methods Stratification factors included sex, clinical node status, and primary size. DFS and OS were estimated univariately by the Kaplan-Meier method, and treatment arms were compared by log-rank test. Time to relapse and CF were estimated by the cumulative incidence method and treatment arms were compared by using Gray's test. Multivariate analyses used Cox proportional hazard models to test for treatment differences after adjusting for stratification factors. Results Of 682 patients accrued, 649 were analyzable for outcomes. DFS and OS were statistically better for RT + FU/MMC versus RT + FU/CDDP (5-year DFS, 67.8% v 57.8%; P = .006; 5-year OS, 78.3% v 70.7%; P = .026). There was a trend toward statistical significance for CFS (P = .05), LRF (P = .087), and CF (P = .074). Multivariate analysis was statistically significant for treatment and clinical node status for both DFS and OS, for tumor diameter for DFS, and for sex for OS. Conclusion CCR with FU/MMC has a statistically significant, clinically meaningful impact on DFS and OS versus induction plus concurrent FU/CDDP, and it has borderline significance for CFS, CF, and LRF. Therefore, RT + FU/MMC remains the preferred standard of care. J Clin Oncol 30: 4344-4351. (C) 2012 by American Society of Clinical Oncology C1 [Gunderson, Leonard L.] Mayo Clin Arizona, Scottsdale, AZ 85259 USA. [Winter, Kathryn A.; Moughan, Jennifer] Ctr Stat, Radiat Therapy Oncol Grp, Philadelphia, PA USA. [Ajani, Jaffer A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Pedersen, John E.] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. [Benson, Al B., III] Northwestern Univ, Chicago, IL 60611 USA. [Thomas, Charles R., Jr.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Mayer, Robert J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Haddock, Michael G.] Mayo Clin, Rochester, MN USA. [Rich, Tyvin A.] Univ Virginia, Charlottesville, VA USA. [Willett, Christopher G.] Duke Univ, Durham, NC USA. RP Gunderson, LL (reprint author), Mayo Clin Arizona, 13400 E Shea Blvd, Scottsdale, AZ 85259 USA. EM llg.scottsdale@cox.net FU National Cancer Institute [RTOG U10 CA21661, CCOP U10 CA37422] FX Supported by Grants No. RTOG U10 CA21661 and CCOP U10 CA37422 from the National Cancer Institute. NR 28 TC 105 Z9 106 U1 0 U2 11 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 10 PY 2012 VL 30 IS 35 BP 4344 EP 4351 DI 10.1200/JCO.2012.43.8085 PG 8 WC Oncology SC Oncology GA 052KG UT WOS:000312195900016 PM 23150707 ER PT J AU Mack, JW Cronin, A Keating, NL Taback, N Huskamp, HA Malin, JL Earle, CC Weeks, JC AF Mack, Jennifer W. Cronin, Angel Keating, Nancy L. Taback, Nathan Huskamp, Haiden A. Malin, Jennifer L. Earle, Craig C. Weeks, Jane C. TI Associations Between End-of-Life Discussion Characteristics and Care Received Near Death: A Prospective Cohort Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID METASTATIC COLORECTAL-CANCER; PALLIATIVE CARE; OUTCOMES RESEARCH; MENTAL-HEALTH; DISCUSSIONS; SURVEILLANCE; CHEMOTHERAPY; AGGRESSIVENESS; PREFERENCES; PREDICTORS AB Purpose National guidelines recommend that discussions about end-of-life (EOL) care planning happen early for patients with incurable cancer. We do not know whether earlier EOL discussions lead to less aggressive care near death. We sought to evaluate the extent to which EOL discussion characteristics, such as timing, involved providers, and location, are associated with the aggressiveness of care received near death. Patients and Methods We studied 1,231 patients with stage IV lung or colorectal cancer in the Cancer Care Outcomes Research and Surveillance Consortium, a population-and health system-based prospective cohort study, who died during the 15-month study period but survived at least 1 month. Our main outcome measure was the aggressiveness of EOL care received. Results Nearly half of patients received at least one marker of aggressive EOL care, including chemotherapy in the last 14 days of life (16%), intensive care unit care in the last 30 days of life (9%), and acute hospital-based care in the last 30 days of life (40%). Patients who had EOL discussions with their physicians before the last 30 days of life were less likely to receive aggressive measures at EOL, including chemotherapy (P = .003), acute care (P < .001), or any aggressive care (P < .001). Such patients were also more likely to receive hospice care (P < .001) and to have hospice initiated earlier (P < .001). Conclusion Early EOL discussions are prospectively associated with less aggressive care and greater use of hospice at EOL. J Clin Oncol 30: 4387-4395. (C) 2012 by American Society of Clinical Oncology C1 [Mack, Jennifer W.; Cronin, Angel; Taback, Nathan; Weeks, Jane C.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Mack, Jennifer W.] Boston Childrens Hosp, Boston, MA USA. [Keating, Nancy L.; Huskamp, Haiden A.] Harvard Univ, Sch Med, Boston, MA USA. [Keating, Nancy L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Malin, Jennifer L.] Greater Los Angeles Vet Adm Hlth Care Syst, Los Angeles, CA USA. [Malin, Jennifer L.] Univ Calif Los Angeles, Los Angeles, CA USA. [Earle, Craig C.] Ontario Inst Canc Res, Toronto, ON, Canada. RP Mack, JW (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM jennifer_mack@dfci.harvard.edu FU National Cancer Institute (NCI) [U01 CA093344, U01 CA093332, U01 CA093324, U01 CA093348, U01 CA093329, U01 CA093339, U01 CA093326]; Department of Veterans Affairs (VA) [CRS 02-164]; American Cancer Society; National Palliative Care Research Center FX Supported by grants from the National Cancer Institute (NCI) to the Statistical Coordinating Center (U01 CA093344) and to the NCI-supported Primary Data Collection and Research Centers (Dana-Farber Cancer Institute/Cancer Research Network [U01 CA093332], Harvard Medical School/Northern California Cancer Center [U01 CA093324], RAND/University of California at Los Angeles [U01 CA093348], University of Alabama at Birmingham [U01 CA093329], University of Iowa [U01 CA093339], and University of North Carolina [U01 CA093326]); by a Department of Veterans Affairs (VA) grant to the Durham VA Medical Center (CRS 02-164); and by an American Cancer Society Mentored Research Scholar Grant and the National Palliative Care Research Center (J.W.M.). NR 34 TC 109 Z9 109 U1 5 U2 28 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 10 PY 2012 VL 30 IS 35 BP 4387 EP 4395 DI 10.1200/JCO.2012.43.6055 PG 9 WC Oncology SC Oncology GA 052KG UT WOS:000312195900022 PM 23150700 ER PT J AU Seng, S Liu, ZY Chiu, SK Proverbs-Singh, T Sonpavde, G Choueiri, TK Tsao, CK Yu, MG Hahn, NM Oh, WK Galsky, MD AF Seng, Sonia Liu, Ziyue Chiu, Sophia K. Proverbs-Singh, Tracy Sonpavde, Guru Choueiri, Toni K. Tsao, Che-Kai Yu, Menggang Hahn, Noah M. Oh, William K. Galsky, Matthew D. TI Risk of Venous Thromboembolism in Patients With Cancer Treated With Cisplatin: A Systematic Review and Meta-Analysis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CELL LUNG-CANCER; RANDOMIZED PHASE-II; COOPERATIVE-ONCOLOGY-GROUP; ADVANCED GASTRIC-CANCER; DOCETAXEL PLUS CISPLATIN; CLINICAL-TRIALS GROUP; OF-THE-LITERATURE; COMBINATION CHEMOTHERAPY; 1ST-LINE TREATMENT; BREAST-CANCER AB Purpose Several reports suggest that cisplatin is associated with an increased risk of thromboembolism. However, because the excess risk of venous thromboembolic events (VTEs) with cisplatin-based chemotherapy has not been well described, we conducted a systemic review and meta-analysis of randomized controlled trials evaluating the incidence and risk of VTEs associated with cisplatin-based chemotherapy. Methods PubMed was searched for articles published from January 1, 1990, to December 31, 2010. Eligible studies included prospective randomized phase II and III trials evaluating cisplatin-based versus non-cisplatin-based chemotherapy in patients with solid tumors. Data on all-grade VTEs were extracted. Study quality was calculated using Jadad scores. Incidence rates, relative risks (RRs), and 95% CIs were calculated using a random effects model. Results A total of 8,216 patients with various advanced solid tumors from 38 randomized controlled trials were included. The incidence of VTEs was 1.92% (95% CI, 1.07 to 2.76) in patients treated with cisplatin-based chemotherapy and 0.79% (95% CI, 0.45 to 1.13) in patients treated with non-cisplatin-based regimens. Patients receiving cisplatin-based chemotherapy had a significantly increased risk of VTEs (RR, 1.67; 95% CI, 1.25 to 2.23; P = .01). Exploratory subgroup analysis revealed the highest RR of VTEs in patients receiving a weekly equivalent cisplatin dose > 30 mg/m(2) (2.71; 95% CI, 1.17 to 6.30; P = .02) and in trials reported during 2000 to 2010 (1.72; 95% CI, 1.27 to 2.34; P = .01). Conclusion Cisplatin is associated with a significant increase in the risk of VTEs in patients with advanced solid tumors when compared with non-cisplatin-based chemotherapy. J Clin Oncol 30:4416-4426. (c) 2012 by American Society of Clinical Oncology C1 [Galsky, Matthew D.] Mt Sinai Med Ctr, Mt Sinai Sch Med, Tisch Canc Inst, New York, NY 10029 USA. [Choueiri, Toni K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Liu, Ziyue; Hahn, Noah M.] Indiana Univ Sch Med, Indianapolis, IN USA. [Sonpavde, Guru] Baylor Coll Med, Houston, TX 77030 USA. [Yu, Menggang] Univ Wisconsin, Sch Med, Madison, WI USA. RP Galsky, MD (reprint author), Mt Sinai Med Ctr, Mt Sinai Sch Med, Tisch Canc Inst, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM matthew.galsky@mssm.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 FU Bellicum Pharmaceuticals; Bristol-Myers Squibb; Celgene; Cephalon; Novartis; Pfizer; Dendreon; Genentech; Exelixis; Merck; Millennium Pharmaceuticals; sanofi-aventis FX Research Funding: Guru Sonpavde, Bellicum Pharmaceuticals, Bristol-Myers Squibb, Celgene, Cephalon, Novartis, Pfizer; Noah M. Hahn, Bristol-Myers Squibb, Celgene, Dendreon, Genentech, Exelixis, Merck, Millennium Pharmaceuticals, Novartis, sanofi-aventis NR 76 TC 52 Z9 54 U1 2 U2 12 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 DEC 10 PY 2012 VL 30 IS 35 BP 4416 EP 4426 DI 10.1200/JCO.2012.42.4358 PG 11 WC Oncology SC Oncology GA 052KG UT WOS:000312195900026 PM 23150697 ER PT J AU Burstein, HJ Piccart-Gebhart, MJ Perez, EA Hortobagyi, GN Wolmark, N Albain, KS Norton, L Winer, EP Hudis, CA AF Burstein, Harold J. Piccart-Gebhart, Martine J. Perez, Edith A. Hortobagyi, Gabriel N. Wolmark, Norman Albain, Kathy S. Norton, Larry Winer, Eric P. Hudis, Clifford A. TI Ongoing Debate: Anthracyclines and Adjuvant Treatment of Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 [Burstein, Harold J.; Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Piccart-Gebhart, Martine J.] Inst Jules Bordet, B-1000 Brussels, Belgium. [Perez, Edith A.] Mayo Clin, Jacksonville, FL 32224 USA. [Hortobagyi, Gabriel N.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Wolmark, Norman] Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. [Wolmark, Norman] Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. [Albain, Kathy S.] Loyola Univ Chicago Stritch Sch Med, Maywood, IL USA. [Norton, Larry; Hudis, Clifford A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Burstein, HJ (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. OI Norton, Larry/0000-0003-3701-9250 NR 2 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 10 PY 2012 VL 30 IS 35 BP 4446 EP 4446 DI 10.1200/JCO.2012.45.9677 PG 1 WC Oncology SC Oncology GA 052KG UT WOS:000312195900032 ER PT J AU Tung, N Garber, JE Lincoln, A Domchek, SM AF Tung, Nadine Garber, Judy E. Lincoln, Anne Domchek, Susan M. TI Frequency of Triple-Negative Breast Cancer in BRCA1 Mutation Carriers: Comparison Between Common Ashkenazi Jewish and Other Mutations SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID ESTROGEN C1 [Tung, Nadine; Lincoln, Anne] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Garber, Judy E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Domchek, Susan M.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Tung, Nadine; Garber, Judy E.] Harvard Univ, Sch Med, Boston, MA USA. RP Tung, N (reprint author), Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 9 TC 3 Z9 3 U1 1 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 10 PY 2012 VL 30 IS 35 BP 4447 EP 4448 DI 10.1200/JCO.2012.44.5635 PG 2 WC Oncology SC Oncology GA 052KG UT WOS:000312195900033 PM 23091104 ER PT J AU Bydlon, TM Barry, WT Kennedy, SA Brown, JQ Gallagher, JE Wilke, LG Geradts, J Ramanujam, N AF Bydlon, Torre M. Barry, William T. Kennedy, Stephanie A. Brown, J. Quincy Gallagher, Jennifer E. Wilke, Lee G. Geradts, Joseph Ramanujam, Nimmi TI Advancing Optical Imaging for Breast Margin Assessment: An Analysis of Excisional Time, Cautery, and Patent Blue Dye on Underlying Sources of Contrast SO PLOS ONE LA English DT Article ID FROZEN-SECTION ANALYSIS; DIFFUSE-REFLECTANCE SPECTROSCOPY; TOUCH PREPARATION CYTOLOGY; CONSERVING SURGERY; COHERENCE TOMOGRAPHY; CONSERVATION SURGERY; LUMPECTOMY MARGINS; RAMAN-SPECTROSCOPY; SURGICAL MARGINS; LOCAL RECURRENCE AB Breast conserving surgery (BCS) is a recommended treatment for breast cancer patients where the goal is to remove the tumor and a surrounding rim of normal tissue. Unfortunately, a high percentage of patients return for additional surgeries to remove all of the cancer. Post-operative pathology is the gold standard for evaluating BCS margins but is limited due to the amount of tissue that can be sampled. Frozen section analysis and touch-preparation cytology have been proposed to address the surgical needs but also have sampling limitations. These issues represent an unmet clinical need for guidance in resecting malignant tissue intra-operatively and for pathological sampling. We have developed a quantitative spectral imaging device to examine margins intra-operatively. The context in which this technology is applied (intra-operative or post-operative setting) is influenced by time after excision and surgical factors including cautery and the presence of patent blue dye (specifically Lymphazurin(TM), used for sentinel lymph node mapping). Optical endpoints of hemoglobin ([THb]), fat ([beta-carotene]), and fibroglandular content via light scattering () measurements were quantified from diffuse reflectance spectra of lumpectomy and mastectomy specimens using a Monte Carlo model. A linear longitudinal mixed-effects model was used to fit the optical endpoints for the cautery and kinetics studies. Monte Carlo simulations and tissue mimicking phantoms were used for the patent blue dye experiments. [THb], [beta-carotene], and were affected by < 3.3% error with < 80 mu M of patent blue dye. The percent change in [beta-carotene], , and [beta-carotene]/. was < 14% in 30 minutes, while percent change in [THb] was > 40%. [beta-carotene] and [beta-carotene]/. were the only parameters not affected by cautery. This work demonstrates the importance of understanding the post-excision kinetics of ex-vivo tissue and the presence of cautery and patent blue dye for breast tumor margin assessment, to accurately interpret data and exploit underling sources of contrast. C1 [Bydlon, Torre M.; Kennedy, Stephanie A.; Brown, J. Quincy; Ramanujam, Nimmi] Duke Univ, Dept Biomed Engn, Durham, NC 27706 USA. [Barry, William T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Brown, J. Quincy; Ramanujam, Nimmi] Zenalux, Res Triangle Pk, NC USA. [Gallagher, Jennifer E.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Wilke, Lee G.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI USA. [Geradts, Joseph] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27706 USA. RP Ramanujam, N (reprint author), Duke Univ, Dept Biomed Engn, Durham, NC 27706 USA. EM nimmi@duke.edu RI Brown, J. Quincy/F-6090-2012 FU Department of Defense Breast Cancer Predoctoral Traineeship [W81XWH-04-1-0340]; Department of Defense [W81XWH-05-1-036]; National Institute of Health [1R41CA128160-01]; Duke University's CTSA from NCRR/NIH [1 UL1 RR024128-01] FX This work was supported by the following grants: the Department of Defense Breast Cancer Predoctoral Traineeship W81XWH-04-1-0340, the Department of Defense award W81XWH-05-1-036, National Institute of Health award 1R41CA128160-01, and was supported in part by Duke University's CTSA grant 1 UL1 RR024128-01 from NCRR/NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 65 TC 14 Z9 14 U1 1 U2 32 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 10 PY 2012 VL 7 IS 12 AR e51418 DI 10.1371/journal.pone.0051418 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 052ML UT WOS:000312201900084 PM 23251526 ER PT J AU Mischoulon, D Brill, CD Ameral, VE Fava, M Yeung, AS AF Mischoulon, David Brill, Charlotte D. Ameral, Victoria E. Fava, Maurizio Yeung, Albert S. TI A pilot study of acupuncture monotherapy in patients with major depressive disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Acupuncture; Antidepressant; Monotherapy; Depression ID RANDOMIZED-CONTROLLED-TRIAL; STAR-ASTERISK-D; OUTCOMES AB Background: We have previously shown that a standardized acupuncture augmentation was effective for antidepressant partial responders with major depressive disorder (MDD). This pilot study examines the efficacy and safety of this protocol as monotherapy for MDD. Methods: Thirty outpatients (73% female, mean age 47 +/- 12 yrs) with SCID-diagnosed MDD were recruited and received 8 weeks of standardized 30-minute open acupuncture treatment using 5 specific body points on the arms and legs bilaterally, with manual stimulation every 10 min, and concurrent electroacupuncture (2 Hz current) at two points along the midline of the head. Subjects were assigned to once-weekly (n=21) or twice-weekly (n=9) treatment, depending on preference. Change in Hamilton-D-17 score was the primary outcome measure, and positive response to treatment (defined as >= 50% improvement in HAM-D-17 scores compared to baseline) was the secondary outcome measure. Results: HAM-D-17 scores decreased from 19.1 +/- 4.4 to 9.9 +/- 6.3 (p<0.001) in the once-weekly acupuncture group, and from 21.9 +/- 5.3 to 14.3 +/- 6.1 (p=0.012) in the twice-weekly acupuncture group. Improvement did not differ significantly between treatment arms. Response rates were 62% for the once-weekly acupuncture group and 22% for the twice-weekly acupuncture group (NS). Twenty patients (14 in weekly treatment group and 6 in twice-weekly treatment group) completed the study. The most common side effects included mild soreness/pain (n=13), and mild bleeding (n=16) at the needle site. Limitations: Open design and small sample. Conclusions: Standardized acupuncture treatment was safe, well-tolerated and effective, suggesting good feasibility in outpatient settings. Replication in controlled trials is warranted. (C) 2012 Elsevier B. V. All rights reserved. C1 [Mischoulon, David; Brill, Charlotte D.; Ameral, Victoria E.; Fava, Maurizio; Yeung, Albert S.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Yeung, AS (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM ayeung@partners.org FU MGH; Abbott Laboratories; Alkermes; Aspect Medical Systems; Astra-Zeneca; BioResearch; BrainCells, Inc.; Bristol-Myers Squibb Company; Cephalon; Clinical Trial Solutions,LLC; Eli Lilly Company; EnVivo Pharmaceuticals, Inc.; Forest Pharmaceuticals Inc.; Ganeden; GlaxoSmithKline; J & J Pharmaceuticals; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; NARSAD; NCCAM; NIDA; NIMH; Novartis; Organon Inc.; PamLab, LLC; Pfizer Inc; Pharmavite; Roche; Sanofi-Aventis; Shire; Solvay Pharmaceuticals, Inc.; Synthelabo; Wyeth-Ayerst Laboratories; Nordic Naturals FX This study was supported by the MGH Depression Clinical and Research Program's clinical practice revenues. Only the authors of the manuscript were involved in the study design, collection, analysis and interpretation of data, writing of the report, and the decision to submit the paper for publication.; Dr. Fava has received research support from Abbott Laboratories, Alkermes, Aspect Medical Systems, Astra-Zeneca, BioResearch, BrainCells, Inc., Bristol-Myers Squibb Company, Cephalon, Clinical Trial Solutions,LLC, Eli Lilly & Company, EnVivo Pharmaceuticals, Inc., Forest Pharmaceuticals Inc., Ganeden, GlaxoSmithKline, J & J Pharmaceuticals, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, NARSAD, NCCAM, NIDA, NIMH, Novartis, Organon Inc., PamLab, LLC, Pfizer Inc, Pharmavite, Roche, Sanofi-Aventis, Shire, Solvay Pharmaceuticals, Inc., Synthelabo, and Wyeth-Ayerst Laboratories. He has served as an advisor and consultant to Abbott Laboratories, Affectis Pharmaceuticals AG, Amarin, Aspect Medical Systems, Astra-Zeneca, Auspex Pharmaceuticals, Bayer AG, Best Practice Project Management, Inc, BioMarin Pharmaceuticals, Inc., Biovail Pharmaceuticals, Inc., BrainCells, Inc, Bristol-Myers Squibb Company, Cephalon, Clinical Trials Solutions, LLC, CNS Response, Compellis, Cypress Pharmaceuticals, Dov Pharmaceuticals, Eisai, Inc., Eli Lilly & Company, EPIX Pharmaceuticals, Euthymics Bioscience, Inc., Fabre-Kramer, Pharmaceuticals, Inc., Forest Pharmaceuticals Inc., GlaxoSmithKline, Grunenthal GmBH, Janssen Pharmaceutica, Jazz Pharmaceuticals, J & J Pharmaceuticals, Knoll Pharmaceutical Company, Labopharm, Lorex Pharmaceuticals, Lundbeck, MedAvante Inc., Merck, Methylation Sciences, Neuronetics, Novartis, Nutrition 21, Organon Inc., PamLab, LLC, Pfizer Inc, PharmaStar, Pharmavite, Precision Human Bio-laboratory, Prexa Pharmaceuticals, Inc., PsychoGenics, Psylin Neurosciences, Inc., Ridge Diagnostics, Inc., Roche, Sanofi-Aventis, Sepracor, Schering-Plough, Solvay Pharmaceuticals, Inc., Somaxon, Somerset Pharmaceuticals, Synthelabo, Takeda, Tetragenex, TransForm Pharmaceuticals, Inc., Transcept Pharmaceuticals, Vanda Pharmaceuticals Inc, Wyeth-Ayerst Laboratories. He has received speaking and publishing honoraria from Adamed, Co., Advanced Meeting Partners, American Psychiatric Association, American Society of Clinical Psychopharmacology, Astra-Zeneca, Belvoir, Boehringer-Ingelheim, Bristol-Myers Squibb Company, Cephalon, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithKline, Imedex, Novartis, Organon Inc., Pfizer Inc, PharmaStar, MGH Psychiatry Academy/Primedia, MGH Psychiatry Academy/Reed-Elsevier, UBC, and Wyeth-Ayerst Laboratories. He holds equity in Compellis. He currently holds a patent for SPCD and a patent application for a combination of azapirones and bupropion in MDD, and has received copyright royalties for the MGH CPFQ, SFI, ATRQ, DESS, and SAFER diagnostic instruments.; Dr. Mischoulon has received research support from Nordic Naturals and Ganeden. He has served as a consultant to Bristol-Meyers-Squibb Company. He has received writing honoraria from Pamlab and Nordic Naturals and speaking honoraria from Nordic Naturals. He has received royalties from Back Bay Scientific for PMS Escape, and royalties from Lippincott Williams & Wilkins, for textbook "Natural Medications for Psychiatric Disorders: Considering the Alternatives" (David Mischoulon and Jerrold F Rosenbaum, Eds.). He has received honoraria from Reed Medical Education (a company working as a logistics collaborator for the MGH Psychiatry Academy). The education programs conducted by the MGH Psychiatry Academy were supported through Independent Medical Education (IME) grants from pharmaceutical companies co-supporting programs along with participant tuition. Commercial entities currently supporting the MGH Psychiatry Academy are listed on the Academy's website www.mghcme.org. NR 23 TC 10 Z9 12 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD DEC 10 PY 2012 VL 141 IS 2-3 BP 469 EP 473 DI 10.1016/j.jad.2012.03.023 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 039IF UT WOS:000311237700045 PM 22521855 ER PT J AU Efstathiou, JA AF Efstathiou, Jason A. TI Postoperative radiation for prostate cancer SO LANCET LA English DT Editorial Material ID RADICAL PROSTATECTOMY; ADJUVANT RADIOTHERAPY; SALVAGE RADIOTHERAPY; THERAPY; METASTASES; TRIAL C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Efstathiou, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. EM jefstathiou@partners.org NR 13 TC 3 Z9 3 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD DEC 8 PY 2012 VL 380 IS 9858 BP 1974 EP 1976 DI 10.1016/S0140-6736(12)61608-0 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 051KI UT WOS:000312124900007 PM 23084480 ER PT J AU Voight, BF Kathiresan, S AF Voight, Benjamin F. Kathiresan, Sekar TI Plasma HDL cholesterol and risk of myocardial infarction reply SO LANCET LA English DT Letter C1 [Voight, Benjamin F.; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Dis Prevent Ctr, Boston, MA 02114 USA. RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Cardiovasc Dis Prevent Ctr, Boston, MA 02114 USA. EM skathiresan@partners.org NR 5 TC 0 Z9 0 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD DEC 8 PY 2012 VL 380 IS 9858 BP 1991 EP 1991 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 051KI UT WOS:000312124900020 ER PT J AU Giugliano, RP Desai, NR Kohli, P Rogers, WJ Somaratne, R Huang, F Liu, T Mohanavelu, S Hoffman, EB McDonald, ST Abrahamsen, TE Wasserman, SM Scott, R Sabatine, MS AF Giugliano, Robert P. Desai, Nihar R. Kohli, Payal Rogers, William J. Somaratne, Ransi Huang, Fannie Liu, Thomas Mohanavelu, Satishkumar Hoffman, Elaine B. McDonald, Shannon T. Abrahamsen, Timothy E. Wasserman, Scott M. Scott, Robert Sabatine, Marc S. CA LAPLACE-TIMI 57 Investigators TI Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, phase 2 study SO LANCET LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; CORONARY-HEART-DISEASE; FAMILIAL HYPERCHOLESTEROLEMIA; LDL CHOLESTEROL; PCSK9; THERAPY; GUIDELINES; TRIAL AB Background LDL cholesterol (LDL-C) is a well established risk factor for cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds LDL receptors, targeting them for degradation. We therefore assessed the efficacy, safety, and tolerability of AMG 145, a human monoclonal IgG2 antibody against PCSK9, in stable patients with hypercholesterolemia on a statin. Methods In a phase 2, dose-ranging study done in 78 centres in the USA, Canada, Denmark, Hungary, and Czech Republic, patients (aged 18-80 years) with LDL-C greater than 2.2 mmol/L on a stable dose of statin (with or without ezetimibe), were randomly assigned equally, through an interactive voice response system, to subcutaneous injections of AMG 145 70 mg, 105 mg, or 140 mg, or matching placebo every 2 weeks; or subcutaneous injections of AMG 145 280 mg, 350 mg, or 420 mg, or matching placebo every 4 weeks. Everyone was masked to treatment assignment within the every 2 weeks and every 4 weeks schedules. The primary endpoint was the percentage change in LDL-C concentration from baseline after 12 weeks. Analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01380730. Findings 631 patients with hypercholesterolaemia were randomly assigned to AMG 145 70 mg (n=79), 105 mg (n=79), or 140 mg (n=78), or matching placebo (n=78) every 2 weeks; or AMG 145 280 mg (n=79), 350 mg (n=79), and 420 mg (n=80), and matching placebo (n=79) every 4 weeks. At the end of the dosing interval at week 12, the mean LDL-C concentrations were reduced generally dose dependently by AMG 145 every 2 weeks (ranging from 41.8% to 66.1%; p<0.0001 for each dose vs placebo) and AMG 145 every 4 weeks (ranging from 41.8% to 50.3%; p<0.0001). No treatment-related serious adverse events occurred. The frequencies of treatment-related adverse events were similar in the AMG 145 and placebo groups (39 [8%] of 474 vs 11 [7%] of 155); none of these events were severe or life-threatening. Interpretation The results suggest that PCSK9 inhibition could be a new model in lipid management. Inhibition of PCSK9 warrants assessment in phase 3 clinical trials. C1 [Giugliano, Robert P.; Desai, Nihar R.; Kohli, Payal; Mohanavelu, Satishkumar; Hoffman, Elaine B.; McDonald, Shannon T.; Abrahamsen, Timothy E.; Sabatine, Marc S.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Rogers, William J.] Univ Alabama Birmingham, Birmingham, AL USA. [Somaratne, Ransi; Huang, Fannie; Liu, Thomas; Wasserman, Scott M.; Scott, Robert] Amgen Inc, Thousand Oaks, CA USA. RP Giugliano, RP (reprint author), Brigham & Womens Hosp, TIMI Study Grp, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM rgiugliano@partners.org FU Amgen; Amgen through Brigham and Women's Hospital; AstraZeneca throught Brigham and Women's Hospital; AstraZeneca/Bristol-Myers Squibb Alliance; Bristol-Myers Squibb/Sanofi-Aventis Joint Venture; Daiichi-Sankyo; Genzyme; Sanofi-Aventis; Sanofi-Aventis, Merck; Pfizer; Amgen, Thousand Oaks, CA FX Amgen.; RPG, NRD, PK, SM, EBH, STM, TEA, and MSS received research grant support through Brigham and Women's Hospital for this trial from Amgen. RPG and MSS also have served as consultants for Amgen. WJR received research grant support for participation in this trial from Amgen. RSo, FH, TL, SMW, and RSc are employees of Amgen and own Amgen stock. MSS also received research grant support through Brigham and Women's Hospital from AstraZeneca, AstraZeneca/Bristol-Myers Squibb Alliance, Bristol-Myers Squibb/Sanofi-Aventis Joint Venture, Daiichi-Sankyo, Genzyme, Sanofi-Aventis, Merck, and Pfizer, and received honoraria for consulting from Aegerion, Sanofi-Aventis, GlazoSmithKline, Merck, and Pfizer.; LAPLACE-TIMI 57 was supported by a research grant from Amgen, Thousand Oaks, CA. We thank all the investigators, Data Monitoring and Clinical Endpoint Committee members, and Meera Kodukulla, Amgen, for her editorial support in formatting the report. NR 17 TC 213 Z9 228 U1 5 U2 28 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD DEC 8 PY 2012 VL 380 IS 9858 BP 2007 EP 2017 DI 10.1016/S0140-6736(12)61770-X PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 051KI UT WOS:000312124900031 PM 23141813 ER PT J AU Centurion, VP Huang, F Naureckas, ET Camargo, CA Charbeneau, J Joo, MJ Press, VG Krishnan, JA AF Centurion, Valentin Prieto Huang, Frank Naureckas, Edward T. Camargo, Carlos A., Jr. Charbeneau, Jeffrey Joo, Min J. Press, Valerie G. Krishnan, Jerry A. TI Confirmatory spirometry for adults hospitalized with a diagnosis of asthma or chronic obstructive pulmonary disease exacerbation SO BMC PULMONARY MEDICINE LA English DT Article DE Asthma; COPD; Exacerbation; Hospitalization; Spirometry; Quality improvement ID UNITED-STATES; LUNG-FUNCTION; PRIMARY-CARE; MORTALITY; COPD; PREDICTORS; ACCURACY; QUALITY AB Background: Objective measurement of airflow obstruction by spirometry is an essential part of the diagnosis of asthma or COPD. During exacerbations, the feasibility and utility of spirometry to confirm the diagnosis of asthma or chronic obstructive pulmonary disease (COPD) are unclear. Addressing these gaps in knowledge may help define the need for confirmatory testing in clinical care and quality improvement efforts. This study was designed to determine the feasibility of spirometry and to determine its utility to confirm the diagnosis in patients hospitalized with a physician diagnosis of asthma or COPD exacerbation. Methods: Multi-center study of four academic healthcare institutions. Spirometry was performed in 113 adults admitted to general medicine wards with a physician diagnosis of asthma or COPD exacerbation. Two board-certified pulmonologists evaluated the spirometry tracings to determine the proportion of patients able to produce adequate quality spirometry data. Findings were interpreted to evaluate the utility of spirometry to confirm the presence of obstructive lung disease, according to the 2005 European Respiratory Society/American Thoracic Society recommendations. Results: There was an almost perfect agreement for acceptability (K = 0.92) and reproducibility (K = 0.93) of spirometry tracings. Three-quarters (73%) of the tests were interpreted by both pulmonologists as being of adequate quality. Of these adequate quality tests, 22% did not present objective evidence of obstructive lung disease. Obese patients (BMI >= 30 kg/m(2)) were more likely to produce spirometry tracings with no evidence of obstructive lung disease, compared to non-obese patients (33% vs. 8%, p = 0.007). Conclusions: Adequate quality spirometry can be obtained in most hospitalized adults with a physician diagnosis of asthma or COPD exacerbation. Confirmatory spirometry could be a useful tool to help reduce overdiagnosis of obstructive lung disease, especially among obese patients. C1 [Centurion, Valentin Prieto; Charbeneau, Jeffrey; Joo, Min J.; Krishnan, Jerry A.] Univ Illinois, Chicago, IL 60607 USA. [Huang, Frank; Naureckas, Edward T.; Press, Valerie G.] Univ Chicago Med, Chicago, IL USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Krishnan, Jerry A.] Univ Illinois Hosp & Hlth Sci Syst, Chicago, IL 60612 USA. RP Krishnan, JA (reprint author), Univ Illinois, Chicago, IL 60607 USA. EM jakris@uic.edu FU Agency for Healthcare Research and Quality [R13 HS017894]; National Heart, Lung, and Blood Institute [HL1011618] FX Funding for this study was received from the Agency for Healthcare Research and Quality (R13 HS017894) and National Heart, Lung, and Blood Institute (HL1011618). The sponsors had no role in the design of the study, collection and analysis of the data, or in the preparation of the manuscript. NR 28 TC 6 Z9 6 U1 1 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2466 J9 BMC PULM MED JI BMC Pulm. Med. PD DEC 7 PY 2012 VL 12 AR 73 DI 10.1186/1471-2466-12-73 PG 7 WC Respiratory System SC Respiratory System GA 067GI UT WOS:000313281800001 ER PT J AU Shen, KZ Johnson, SW AF Shen, Ke-Zhong Johnson, Steven W. TI Chronic dopamine depletion augments the functional expression of K-ATP channels in the rat subthalamic nucleus SO NEUROSCIENCE LETTERS LA English DT Article DE ATP-sensitive K+ channel; Subthalamic nucleus; N-Methyl-D-aspartate; Sulfonylurea; Tolbutamide; Brain slice ID SENSITIVE POTASSIUM CHANNELS; NEURONS IN-VITRO; PARKINSONS-DISEASE; BASAL GANGLIA; BRAIN; 6-HYDROXYDOPAMINE; RESPONSES; PALLIDUM; PATHWAY; GABA AB Symptoms of Parkinson's disease caused by dopamine depletion are associated with burst firing in the subthalamic nucleus (STN). Moreover, regularization or suppression of STN neuronal activity is thought to improve symptoms of Parkinson's disease. We reported recently that N-methyl-D-aspartate (NMDA) receptor stimulation of rat STN neurons evokes ATP-sensitive K+ (K-ATP) current via a Ca2+-and nitric oxide-dependent mechanism. The present studies were done to determine whether or not K-ATP channel function in STN neurons is altered in a model of chronic dopamine depletion. Brain slices were prepared from rats with unilateral dopamine depletion caused by intracerebral 6-hydroxydopamine (6-OHDA) injections. Whole-cell patch-clamp recordings showed that NMDA evoked more outward current at -70 mV and greater positive slope conductance in STN neurons located ipsilateral to 6-OHDA treatment compared to neurons located contralateral. Moreover, extracellular, loose-patch recordings showed that NMDA increased spontaneous firing rate in STN neurons in slices from normal rats, whereas NMDA produced a tolbutamide-sensitive inhibition of firing rate in STN neurons located ipsilateral to 6-OHDA treatment. These results show that K-ATP channel function in STN neurons is up-regulated by chronic dopamine deficiency. We suggest that K-ATP channel activation in the STN might benefit symptoms of Parkinson's disease. Published by Elsevier Ireland Ltd. C1 [Shen, Ke-Zhong; Johnson, Steven W.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Johnson, Steven W.] Portland VA Med Ctr, Portland, OR 97207 USA. RP Johnson, SW (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. EM johnsost@ohsu.edu FU USPHS [NS38715]; Portland Veterans Affairs Parkinson's Disease Research, Education, and Clinical Center FX This work was supported by USPHS grant NS38715 and by the Portland Veterans Affairs Parkinson's Disease Research, Education, and Clinical Center. NR 25 TC 3 Z9 3 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD DEC 7 PY 2012 VL 531 IS 2 BP 104 EP 108 DI 10.1016/j.neulet.2012.10.030 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 058CX UT WOS:000312612800009 PM 23127848 ER EF