FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Lachin, JM Orchard, TJ Nathan, DM AF Lachin, John M. Orchard, Trevor J. Nathan, David M. CA DCCT EDIC Res Grp TI Update on Cardiovascular Outcomes at 30 Years of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study SO DIABETES CARE LA English DT Article ID INTIMA-MEDIA THICKNESS; GLUCOSE CONTROL; TYPE-1; DISEASE; MELLITUS; THERAPY; RISK; NEPHROPATHY; PROGRESSION; TRIAL AB OBJECTIVETo describe the beneficial long-term effects of an average of 6.5 years of intensive diabetes therapy (INT) in type 1 diabetes on measures of atherosclerosis, cardiac structure and function, and clinical cardiovascular events observed in the Diabetes Control and Complications Trial (DCCT) and the Epidemiology of Diabetes Interventions and Complications (EDIC) study.RESEARCH DESIGN AND METHODSThe DCCT was a randomized clinical trial of 1,441 participants assigned to receive INT or conventional therapy (CON). It was conducted between 1983-1993 with an average follow-up of 6.5 years. EDIC (1994-present) is an observational follow-up of the DCCT cohort. Cardiovascular events have been recorded throughout. During EDIC common carotid intima-media thickness (IMT) was measured with ultrasound, coronary artery calcification with computed tomography, and cardiac structure and function with cardiac magnetic resonance imaging.RESULTSDCCT INT and lower levels of HbA(1c) during DCCT/EDIC were associated with thinner carotid IMT, less coronary calcification, and a lower incidence of clinical cardiovascular events including myocardial infarction, stroke, and cardiac death. While there were no significant differences in cardiac structure and function between the former INT and CON groups, they were significantly associated with higher HbA(1c) during DCCT/EDIC.CONCLUSIONSDCCT INT and the attendant 6.5 years of lower HbA(1c) had long-term salutary effects on the development and progression of atherosclerosis and cardiovascular disease during the subsequent follow-up during EDIC. C1 [Lachin, John M.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Orchard, Trevor J.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Nathan, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Diabet, Boston, MA USA. [Nathan, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Lachin, JM (reprint author), George Washington Univ, Ctr Biostat, Rockville, MD USA. EM jml@bsc.gwu.edu OI orchard, trevor/0000-0001-9552-3215; Lachin, John/0000-0001-9838-2841 FU Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases [U01-DK-094176, U01-DK-094157]; National Eye Institute; National Institute of Neurological Disorders and Stroke; Genetic Clinical Research Centers Program; Clinical and Translational Science Center Program, Bethesda, MD FX The DCCT/EDIC has been supported by U01 Cooperative Agreement grants (1982-1993, 2011-2016) and contracts (1982-2011) with the Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases (current grant numbers U01-DK-094176 and U01-DK-094157) and through support of the National Eye Institute, the National Institute of Neurological Disorders and Stroke, the Genetic Clinical Research Centers Program (1993-2007), and Clinical and Translational Science Center Program (2006-present), Bethesda, MD. NR 19 TC 55 Z9 57 U1 0 U2 8 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2014 VL 37 IS 1 BP 39 EP 43 DI 10.2337/dc13-2116 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 275KV UT WOS:000328676000019 PM 24356596 ER PT J AU Silva, PS Cavallerano, JD Tolls, D Omar, A Thakore, K Patel, B Sehizadeh, M Tolson, AM Sun, JK Aiello, LM Aiello, LP AF Silva, Paolo S. Cavallerano, Jerry D. Tolls, Dorothy Omar, Ahmed Thakore, Komal Patel, Bina Sehizadeh, Mina Tolson, Ann M. Sun, Jennifer K. Aiello, Lloyd M. Aiello, Lloyd Paul TI Potential Efficiency Benefits of Nonmydriatic Ultrawide Field Retinal Imaging in an Ocular Telehealth Diabetic Retinopathy Program SO DIABETES CARE LA English DT Article ID JOSLIN VISION NETWORK; PHOTOGRAPHY AB OBJECTIVETo compare efficiency of nonmydriatic ultrawide field retinal imaging (UWFI) and nonmydriatic fundus photography (NMFP) in a diabetic retinopathy (DR) ocular telehealth program.RESEARCH DESIGN AND METHODSPatients in this retrospective, comparative cohort study underwent NMFP and UWFI between 1 November 2011 and 1 November 2012. Images were evaluated for DR and diabetic macular edema (DME) by certified graders using a standard protocol at a centralized reading center. Identification of DR, image evaluation time, and rate of ungradable eyes were compared.RESULTSNMFP and UWFI were performed in 1,633 and 2,170 consecutive patients, respectively. No statistically significant differences were found between groups regarding age, diabetes duration, sex, ethnicity, or insulin use. The ungradable rate per patient for DR (2.9 vs. 9.9%, P < 0.0001) and DME (3.8 vs. 8.8%, P < 0.0001) was lower with UWFI than with NMFP. With UWFI, the median image evaluation time per patient was reduced from 12.8 to 9.2 min (P < 0.0001). The identification of patients with DR (38.4 vs. 33.8%) and vision-threatening DR (14.5 vs. 11.9%) was increased with UWFI versus NMFP. In a consecutive subgroup of 502 eyes of 301 patients with DR, the distribution of peripheral retinal lesions outside Early Treatment Diabetic Retinopathy Study fields suggested a more severe DR level in 9.0% (45 eyes).CONCLUSIONSIn a standardized DR ocular telehealth program, nonmydriatic UWFI reduced the ungradable rate by 71% (to <3%) and reduced image evaluation time by 28%. DR was identified 17% more frequently after UWFI, and DR peripheral lesions suggested a more severe DR level in 9%. These data suggest that UWFI may improve efficiency of ocular telehealth programs evaluating DR and DME. C1 [Silva, Paolo S.; Cavallerano, Jerry D.; Sun, Jennifer K.; Aiello, Lloyd M.; Aiello, Lloyd Paul] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Silva, Paolo S.; Cavallerano, Jerry D.; Tolls, Dorothy; Omar, Ahmed; Thakore, Komal; Patel, Bina; Sehizadeh, Mina; Tolson, Ann M.; Sun, Jennifer K.; Aiello, Lloyd M.; Aiello, Lloyd Paul] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. [Omar, Ahmed] Assiut Univ, Fac Med, Dept Ophthalmol, Assiut, Egypt. [Patel, Bina] New England Coll Optometry, Boston, MA USA. RP Silva, PS (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. EM paoloantonio.silva@joslin.harvard.edu FU Amelia Peabody Charitable Fund FX This work was supported in part by grant funding from the Amelia Peabody Charitable Fund to the Joslin Diabetes Center. One of the two Optos P200MA instruments used in this study was provided by Optos (Fife, U.K.) to the Joslin Diabetes Center on temporary loan. No additional outside funding was received for the performance of the research presented in this report. The JVN technology was developed at the Joslin Diabetes Center. All the authors are employees of the Joslin Diabetes Center. NR 14 TC 20 Z9 21 U1 0 U2 8 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2014 VL 37 IS 1 BP 50 EP 55 DI 10.2337/dc13-1292 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 275KV UT WOS:000328676000021 PM 23939541 ER PT J AU Krolewski, AS Niewczas, MA Skupien, J Gohda, T Smiles, A Eckfeldt, JH Doria, A Warram, JH AF Krolewski, Andrzej S. Niewczas, Monika A. Skupien, Jan Gohda, Tomhito Smiles, Adam Eckfeldt, Jon H. Doria, Alessandro Warram, James H. TI Early Progressive Renal Decline Precedes the Onset of Microalbuminuria and Its Progression to Macroalbuminuria SO DIABETES CARE LA English DT Article ID GLOMERULAR-FILTRATION-RATE; TNF RECEPTORS 1; URIC-ACID; CYSTATIN-C; BLOOD-PRESSURE; FOLLOW-UP; DISEASE; RISK; NEPHROPATHY AB OBJECTIVEProgressive decrease in the glomerular filtration rate (GFR), or renal decline, in type 1 diabetes (T1D) is observed in patients with macroalbuminuria. However, it is unknown whether this decline begins during microalbuminuria (MA) or normoalbuminuria (NA).RESEARCH DESIGN AND METHODSThe study group (second Joslin Kidney Study) comprises patients with T1D and NA (n = 286) or MA (n = 248) who were followed for 4-10 years (median 8 years). Serial measurements (median 6, range 3-16) of serum creatinine and cystatin C were used jointly to estimate GFR (eGFRcr-cys) and assess its trajectories during follow-up.RESULTSRenal decline (progressive eGFRcr-cys loss of at least 3.3% per year) occurred in 10% of the NA and 35% of the MA (P < 0.001). In both groups, the strongest determinants of renal decline were baseline serum concentrations of uric acid (P < 0.001) and tumor necrosis factor receptor 1 or 2 (TNFR-1 or -2, P < 0.001). Other significant risk factors included baseline HbA(1c), age/diabetes duration, and systolic blood pressure. Relative impacts of these determinants were similar in NA and MA. Renal decline was not associated with sex or baseline serum concentration of TNF-, IL-6, IL-8, IP-10, MCP-1, VCAM, ICAM, Fas, or FasL.CONCLUSIONSRenal decline in T1D begins during NA and it is determined by multiple factors, similar to MA. Thus, this early decline is the primary disease process leading to impaired renal function in T1D. Changes in albumin excretion rate, such as the onset of MA or its progression to macroalbuminuria, are either caused by or develop in parallel to the early renal decline. C1 [Krolewski, Andrzej S.; Niewczas, Monika A.; Skupien, Jan; Gohda, Tomhito; Smiles, Adam; Doria, Alessandro; Warram, James H.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Krolewski, Andrzej S.; Niewczas, Monika A.; Skupien, Jan; Gohda, Tomhito; Doria, Alessandro] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Skupien, Jan] Jagiellonian Univ, Coll Med, Dept Metab Dis, Krakow, Poland. [Gohda, Tomhito] Juntendo Univ, Sch Med, Dept Internal Med, Div Nephrol, Tokyo 113, Japan. [Eckfeldt, Jon H.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM andrzej.krolewski@joslin.harvard.edu FU National Institutes of Health [DK-41526] FX This study was supported by National Institutes of Health Grant DK-41526. NR 27 TC 50 Z9 50 U1 0 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2014 VL 37 IS 1 BP 226 EP 234 DI 10.2337/dc13-0985 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 275KV UT WOS:000328676000044 PM 23939543 ER PT J AU Ritholz, MD Beste, M Edwards, SS Beverly, EA Atakov-Castillo, A Wolpert, HA AF Ritholz, M. D. Beste, M. Edwards, S. S. Beverly, E. A. Atakov-Castillo, A. Wolpert, H. A. TI Impact of continuous glucose monitoring on diabetes management and marital relationships of adults with Type 1 diabetes and their spouses: a qualitative study SO DIABETIC MEDICINE LA English DT Article ID INSULIN PUMP THERAPY; PREDICTORS; CHILDREN; BENEFIT; FAMILY AB AimsTo examine the impact of continuous glucose monitoring on diabetes management and marital relationships of adults with Type1 diabetes and their spouses. MethodsNine younger (30-49years) and 11 older (50-70years) patients with Type1 diabetes and 14 spouses participated in eight focus groups specific to age and role (patient or spouse). Audio-recorded data were transcribed, coded and analysed using thematic analysis and aided by NVivo software. ResultsQualitative analysis revealed participants perceived continuous glucose monitoring as positively influencing hypoglycaemia management by decreasing spouses' anxiety, vigilance and negative experiences. Participants also described continuous glucose monitoring as promoting collaborative diabetes management and increasing spousal understanding of diabetes, especially when planning and managing pregnancy. Couples' conflicts occurred when (1) patients assumed sole responsibility for continuous glucose monitoring and/or did not respond to night-time glucose alarms and (2) spouses did not understand alarms and felt frustrated and helpless to assist patients. ConclusionsOur findings suggest that continuous glucose monitoring may positively impact collaborative diabetes management and marital relationships of patients with Type1 diabetes and their spouses. However, reluctance to collaborate and lack of understanding may contribute to couples' conflicts around continuous glucose monitoring. Our findings have important implications for clinical care and point to the need for interventions that include spouses in continuous glucose monitoring training to increase their understanding of continuous glucose monitoring, minimize risk for spousal conflict and enhance collaborative diabetes management. Further studies are needed to explore these issues in more detail and depth with larger and more diverse populations. C1 [Ritholz, M. D.; Beste, M.; Edwards, S. S.; Beverly, E. A.; Atakov-Castillo, A.; Wolpert, H. A.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Ritholz, M. D.; Beverly, E. A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Ritholz, M. D.] Boston Childrens Hosp, Dept Psychiat, Boston, MA USA. [Beverly, E. A.] Ohio Univ, Heritage Coll Osteopath Med, Dept Social Med, Boston, MA USA. [Wolpert, H. A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Ritholz, MD (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM marilyn.ritholz@joslin.harvard.edu FU Abbott Diabetes Care FX HAW has been paid for consulting services to Animas and Becton & Dickinson and received grant support from Abbott Diabetes Care. All other authors have nothing to declare. NR 21 TC 0 Z9 0 U1 2 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0742-3071 EI 1464-5491 J9 DIABETIC MED JI Diabetic Med. PD JAN PY 2014 VL 31 IS 1 BP 47 EP 54 DI 10.1111/dme.12276 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 268ZS UT WOS:000328210100010 PM 23819557 ER PT J AU Faustman, DL AF Faustman, Denise L. TI Why were we wrong for so long? The pancreas of type 1 diabetic patients commonly functions for decades SO DIABETOLOGIA LA English DT Editorial Material DE Autoimmunity; Bacillus Calmette-Guerin; C-peptide; Insulin; Islets of Langerhans; Long-term diabetes; Regeneration; Type 1 diabetes ID ISLET REGENERATION; MELLITUS; REVERSAL AB The type 1 diabetes field has held firm to the dogma that the pancreas is no longer viable, and thus incapable of producing insulin, within 1 to 2 years of diagnosis for the majority of patients. A new study in this issue of Diabetologia (DOI: 10.1007/s00125-013-3067-x), based on a hypersensitive assay, has found detectable C-peptide, a marker of insulin production, in individuals with long-standing type 1 diabetes. This new study confirms and expands a decades-long track record of research finding intact pancreatic islet cells in advanced disease. Because the evidence, stemming back to 1902, was largely histological in nature, it was dismissed as lacking functional corroboration. This new study in patients with long-term diabetes shows appropriate functioning of pancreatic islet cells after exposure to a mixed-meal stimulus. The weight of evidence now makes it clear that a large fraction of patients with long-standing diabetes have low level, but persistent functioning of pancreatic islet cells enduring more than a decade after disease onset. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Immunobiol Lab, Boston, MA 02129 USA. RP Faustman, DL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Immunobiol Lab, Bldg 149,13th St,Room 3602, Boston, MA 02129 USA. EM Faustman@helix.mgh.harvard.edu NR 18 TC 4 Z9 4 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD JAN PY 2014 VL 57 IS 1 BP 1 EP 3 DI 10.1007/s00125-013-3104-9 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 270QG UT WOS:000328332900001 PM 24190583 ER PT J AU Soulimane, S Simon, D Herman, WH Lange, C Lee, CMY Colagiuri, S Shaw, JE Zimmet, PZ Magliano, D Ferreira, SRG Dong, YH Zhang, L Jorgensen, T Tuomilehto, J Mohan, V Christensen, DL Kaduka, L Dekker, JM Nijpels, G Stehouwer, CDA Lantieri, O Fujimoto, WY Leonetti, DL McNeely, MJ Borch-Johnsen, K Boyko, EJ Vistisen, D Balkau, B AF Soulimane, Soraya Simon, Dominique Herman, William H. Lange, Celine Lee, Crystal M. Y. Colagiuri, Stephen Shaw, Jonathan E. Zimmet, Paul Z. Magliano, Dianna Ferreira, Sandra R. G. Dong, Yanghu Zhang, Lei Jorgensen, Torben Tuomilehto, Jaakko Mohan, Viswanathan Christensen, Dirk L. Kaduka, Lydia Dekker, Jacqueline M. Nijpels, Giel Stehouwer, Coen D. A. Lantieri, Olivier Fujimoto, Wilfred Y. Leonetti, Donna L. McNeely, Marguerite J. Borch-Johnsen, Knut Boyko, Edward J. Vistisen, Dorte Balkau, Beverley CA DETECT-2 Study Grp DESIR Study Grp TI HbA(1c), fasting and 2 h plasma glucose in current, ex- and never-smokers: a meta-analysis SO DIABETOLOGIA LA English DT Article DE FPG; HbA(1c); 2H-PG; Meta-analysis; Smoking ID CIGARETTE-SMOKING; INSULIN-RESISTANCE; DIABETES-MELLITUS; METABOLIC SYNDROME; HEMOGLOBIN A(1C); RISK-FACTORS; POPULATION; PREVALENCE; TOLERANCE; AUSDIAB AB Aims/Hypothesis The relationships between smoking and glycaemic variables have not been well explored. We compared HbA(1c), fasting plasma glucose (FPG) and 2 h plasma glucose (2H-PG) in current, ex-and never-smokers. Methods This meta-analysis used individual data from 16,886 men and 18,539 women without known diabetes in 12 DETECT-2 consortium studies and in the French Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) and Telecom studies. Means of three glycaemic variables in current, ex-and never-smokers were modelled by linear regression, with study as a random factor. The I 2 statistic was used to evaluate heterogeneity among studies. Results HbA(1c) was 0.10% (95% CI 0.08, 0.12) (1.1 mmol/mol [0.9, 1.3]) higher in current smokers and 0.03% (0.01, 0.05) (0.3 mmol/mol [0.1, 0.5]) higher in ex-smokers, compared with never-smokers. For FPG, there was no significant difference between current and never-smokers (-0.004 mmol/l [-0.03, 0.02]) but FPG was higher in ex-smokers (0.12 mmol/l [ 0.09, 0.14]). In comparison with never-smokers, 2H-PG was lower (-0.44 mmol/l [-0.52, -0.37]) in current smokers, with no difference for ex-smokers (0.02 mmol/l [-0.06, 0.09]). There was a large and unexplained heterogeneity among studies, with I-2 always above 50%; I-2 was little changed after stratification by sex and adjustment for age and BMI. In this study population, current smokers had a prevalence of diabetes that was 1.30% higher as screened by HbA(1c) and 0.52% lower as screened by 2H-PG, in comparison with never-smokers. Conclusion/interpretation Across this heterogeneous group of studies, current smokers had a higher HbA1c and lower 2H-PG than never-smokers. This will affect the chances of smokers being diagnosed with diabetes. C1 [Soulimane, Soraya; Simon, Dominique; Lange, Celine; Balkau, Beverley] INSERM, CESP U1018, F-94807 Villejuif, France. [Soulimane, Soraya; Lange, Celine; Balkau, Beverley] Univ Paris 11, UMRS 1018, Villejuif, France. [Simon, Dominique] Grp Hosp Pitie Salpetriere, Dept Diabet, F-75634 Paris, France. [Simon, Dominique] Univ Paris 06, Paris, France. [Herman, William H.] Univ Michigan, Ann Arbor, MI 48109 USA. [Lee, Crystal M. Y.; Colagiuri, Stephen; DETECT-2 Study Grp] Univ Sydney, Boden Inst Obes Nutr Exercise & Eating Disorders, Sydney, NSW 2006, Australia. [Shaw, Jonathan E.; Zimmet, Paul Z.; Magliano, Dianna] Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia. [Ferreira, Sandra R. G.] Univ Sao Paulo, Sch Publ Hlth, Dept Nutr, Sao Paulo, Brazil. [Dong, Yanghu; Zhang, Lei] Qingdao Endocrine & Diabet Hosp, Dept Endocrinol & Metab, Qingdao, Peoples R China. [Dong, Yanghu; Zhang, Lei] Weifang Med Univ, Weifang, Peoples R China. [Jorgensen, Torben] Capital Reg Denmark, Res Ctr Prevent & Hlth, Glostrup, Denmark. [Tuomilehto, Jaakko] Danube Univ Krems, Krems, Austria. [Tuomilehto, Jaakko] Hosp Univ La Paz, Ctr Vasc Prevent Red RECAVA Grp, Madrid, Spain. [Tuomilehto, Jaakko] King Abdulaziz Univ, Jeddah 21413, Saudi Arabia. [Mohan, Viswanathan] Dr Mohans Diabet Special Ctr, Madras, Tamil Nadu, India. [Mohan, Viswanathan] Madras Diabet Res Fdn, Madras, Tamil Nadu, India. [Christensen, Dirk L.] Univ Copenhagen, Unit Int Hlth, Copenhagen, Denmark. [Kaduka, Lydia] KEMRI, Ctr Publ Hlth Res, Nairobi, Kenya. [Dekker, Jacqueline M.] Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands. [Dekker, Jacqueline M.; Nijpels, Giel] Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands. [Nijpels, Giel] Vrije Univ Amsterdam Med Ctr, Dept Gen Practice & Elderly Care Med, Amsterdam, Netherlands. [Stehouwer, Coen D. A.] Maastricht Univ Med Ctr, Dept Internal Med, Maastricht, Netherlands. [Stehouwer, Coen D. A.] Maastricht Univ Med Ctr, Cardiovasc Res Inst Maastricht CARIM, Maastricht, Netherlands. [Lantieri, Olivier; DESIR Study Grp] IRSA, La Riche, France. [Fujimoto, Wilfred Y.; McNeely, Marguerite J.; Boyko, Edward J.] Univ Washington, Dept Med, Seattle, WA USA. [Leonetti, Donna L.] Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. [Borch-Johnsen, Knut] Holbaek Cent Hosp, Holbaek, Denmark. [Boyko, Edward J.] VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Vistisen, Dorte] Steno Diabet Ctr AS, Gentofte, Denmark. RP Balkau, B (reprint author), INSERM, CESP U1018, 16 Ave Paul Vaillant Couturier, F-94807 Villejuif, France. EM beverley.balkau@inserm.fr RI Shaw, Jonathan/E-7388-2010; OI Shaw, Jonathan/0000-0002-6187-2203; Jorgensen, Torben/0000-0001-9453-2830 FU Australian National Health and Medical Research Council Training Fellowship; Paris-Sud University, France; Australian National Health and Medical Research Council Senior Research Fellowship; DANIDA; Cluster of International Health, University of Copenhagen FX The DETECT-2 project was undertaken on the initiative of the World Health Organization and the International Diabetes Federation. DETECT-2: Task Group. Stephen Colagiuri and Crystal M. Y. Lee (Australia), Knut Borch-Johnsen and Dorte Vistisen (Denmark), Beverley Balkau (France), Jacqueline M. Dekker (the Netherlands). Crystal M. Y. Lee was supported by an Australian National Health and Medical Research Council Training Fellowship. Soraya Soulimane was supported by a PhD grant from Paris-Sud University, France. Jonathan E. Shaw was supported by an Australian National Health and Medical Research Council Senior Research Fellowship. Dirk L. Christensen was supported by a DANIDA grant and by a grant from the Cluster of International Health, University of Copenhagen. NR 42 TC 15 Z9 16 U1 0 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD JAN PY 2014 VL 57 IS 1 BP 30 EP 39 DI 10.1007/s00125-013-3058-y PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 270QG UT WOS:000328332900004 PM 24065153 ER PT J AU Brouwers, O Niessen, PMG Miyata, T Ostergaard, JA Flyvbjerg, A Peutz-Kootstra, CJ Sieber, J Mundel, PH Brownlee, M Janssen, BJA De Mey, JGR Stehouwer, CDA Schalkwijk, CG AF Brouwers, Olaf Niessen, Petra M. G. Miyata, Toshio Ostergaard, Jakob A. Flyvbjerg, Allan Peutz-Kootstra, Carine J. Sieber, Jonas Mundel, Peter H. Brownlee, Michael Janssen, Ben J. A. De Mey, Jo G. R. Stehouwer, Coen D. A. Schalkwijk, Casper G. TI Glyoxalase-1 overexpression reduces endothelial dysfunction and attenuates early renal impairment in a rat model of diabetes SO DIABETOLOGIA LA English DT Article DE Endothelial dysfunction; Glycation; Glyoxalase-1; Methylglyoxal; Renal impairment ID GLYCATION END-PRODUCTS; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; ADHESION MOLECULE; PLASMA-LEVELS; FOLLOW-UP; NEPHROPATHY; COMPLICATIONS; METHYLGLYOXAL; MELLITUS AB Aims/hypothesis In diabetes, advanced glycation end-products (AGEs) and the AGE precursor methylglyoxal (MGO) are associated with endothelial dysfunction and the development of microvascular complications. In this study we used a rat model of diabetes, in which rats transgenically overexpressed the MGO-detoxifying enzyme glyoxalase-I (GLO-I), to determine the impact of intracellular glycation on vascular function and the development of early renal changes in diabetes. Methods Wild-type and Glo1-overexpressing rats were rendered diabetic for a period of 24 weeks by intravenous injection of streptozotocin. Mesenteric arteries were isolated to study ex vivo vascular reactivity with a wire myograph and kidneys were processed for histological examination. Glycation was determined by mass spectrometry and immunohistochemistry. Markers for inflammation, endothelium dysfunction and renal dysfunction were measured with ELISA-based techniques. Results Diabetes-induced formation of AGEs in mesenteric arteries and endothelial dysfunction were reduced by Glo1 overexpression. Despite the absence of advanced nephrotic lesions, early markers of renal dysfunction (i.e. increased glomerular volume, decreased podocyte number and diabetes-induced elevation of urinary markers albumin, osteopontin, kidney-inflammation-molecule-1 and nephrin) were attenuated by Glo1 overexpression. In line with this, downregulation of Glo1 in cultured endothelial cells resulted in increased expression of inflammation and endothelium dysfunction markers. In fully differentiated cultured podocytes incubation with MGO resulted in apoptosis. Conclusions/interpretation This study shows that effective regulation of the GLO-I enzyme is important in the prevention of vascular intracellular glycation, endothelial dysfunction and early renal impairment in experimental diabetes. Modulating the GLO-I pathway therefore may provide a novel approach to prevent vascular complications in diabetes. C1 [Brouwers, Olaf; Niessen, Petra M. G.; Stehouwer, Coen D. A.; Schalkwijk, Casper G.] Maastricht Univ Med Ctr, Dept Internal Med, Div Gen Internal Med, Lab Metab & Vasc Med, NL-6200 MD Maastricht, Netherlands. [Miyata, Toshio] Tohoku Univ, Ctr Translat & Adv Res, Sendai, Miyagi 980, Japan. [Ostergaard, Jakob A.; Flyvbjerg, Allan] Aarhus Univ, Dept Clin Med, Med Res Labs, Aarhus, Denmark. [Ostergaard, Jakob A.; Flyvbjerg, Allan] Aarhus Univ Hosp, Dept Endocrinol & Internal Med, DK-8000 Aarhus, Denmark. [Ostergaard, Jakob A.] Danish Diabet Acad, Aarhus, Denmark. [Peutz-Kootstra, Carine J.] Maastricht Univ Med Ctr, Dept Pathol, NL-6200 MD Maastricht, Netherlands. [Sieber, Jonas; Mundel, Peter H.] Harvard Univ, Sch Med, Boston, MA USA. [Sieber, Jonas; Mundel, Peter H.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Brownlee, Michael] Albert Einstein Coll Med, Int Ctr Diabet Complicat Res, New York, NY USA. [Janssen, Ben J. A.; De Mey, Jo G. R.] Maastricht Univ Med Ctr, Dept Pharmacol, NL-6200 MD Maastricht, Netherlands. [Brouwers, Olaf; Niessen, Petra M. G.; Janssen, Ben J. A.; De Mey, Jo G. R.; Stehouwer, Coen D. A.; Schalkwijk, Casper G.] Maastricht Univ, Cardiovasc Res Inst Maastricht CARIM, Maastricht, Netherlands. RP Brouwers, O (reprint author), Maastricht Univ Med Ctr, Dept Internal Med, Div Gen Internal Med, Lab Metab & Vasc Med, Univ Singel 50,POB 616,Box 14, NL-6200 MD Maastricht, Netherlands. EM olaf.brouwers@maastrichtuniversity.nl RI Miyata, Toshio/A-4872-2010; OI De Mey, Jo G. R./0000-0001-6274-8071 FU Dutch Diabetes Foundation [2005.11.013]; Swiss National Science Foundation [PBBSP3-144160]; National Institutes Health [DK62472, DK57683]; Novo Nordisk Foundation FX This study was partially supported by the Dutch Diabetes Foundation (Grant number 2005.11.013) and further supported by the Swiss National Science Foundation Fellowship PBBSP3-144160 (JS), National Institutes Health Grants DK62472 and DK57683 (PM) and the Danish Diabetes Academy supported by the Novo Nordisk Foundation (JAO). NR 45 TC 33 Z9 34 U1 1 U2 17 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD JAN PY 2014 VL 57 IS 1 BP 224 EP 235 DI 10.1007/s00125-013-3088-5 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 270QG UT WOS:000328332900026 PM 24162587 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Birth-cohort patterns in Crohn's disease and ulcerative colitis SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Article DE birth-cohort study; death rates; environmental risk factors; inflammatory bowel disease; time trends ID INFLAMMATORY-BOWEL-DISEASE; TIME TRENDS; PEPTIC-ULCER; MORTALITY; PERIOD; RATES; AGE AB AimTo test the long-term time trends of mortality from inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), for the presence of birth-cohort phenomena.MethodsWe analyzed mortality data from the national statistical offices of Canada, England and Wales, Italy, the Netherlands, Switzerland, and the USA for the past 60-80 years. Age-specific rates of death were plotted against the period of death, as period-age contours, and against the period of birth, as cohort-age contours.ResultsIn all six countries alike, the general time trends of IBD have been shaped by an underlying birth-cohort pattern. This pattern was also observed in the data of CD and UC analyzed separately. UC mortality increased in all generations born during the 19th century. It peaked among generations born shortly before the turn of the century and then decreased in all subsequent generations born throughout the 20th century. Compared with UC, the birth-cohort pattern of CD was delayed by 30-50 years.ConclusionIn addition to one risk factor responsible for the general occurrence of IBD and possibly UC alone, there exists at least one additional risk factor responsible for CD. Exposure to both separate risk factors must occur during early life. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Div Gastroenterol, Portland VA Med Ctr, Portland, OR 97239 USA. RP Sonnenberg, A (reprint author), Oregon Hlth & Sci Univ, Div Gastroenterol, Portland VA Med Ctr GI P3, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 12 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-691X EI 1473-5687 J9 EUR J GASTROEN HEPAT JI Eur. J. Gastroenterol. Hepatol. PD JAN PY 2014 VL 26 IS 1 BP 19 EP 25 DI 10.1097/01.meg.0000435547.11908.97 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 262UR UT WOS:000327763900004 PM 24216571 ER PT J AU Kozel, BA Danback, JR Waxler, JL Knutsen, RH de las Fuentes, L Reusz, GS Kis, E Bhatt, AB Pober, BR AF Kozel, Beth A. Danback, Joshua R. Waxler, Jessica L. Knutsen, Russell H. de las Fuentes, Lisa Reusz, Gyorgy S. Kis, Eva Bhatt, Ami B. Pober, Barbara R. TI Williams Syndrome Predisposes to Vascular Stiffness Modified by Antihypertensive Use and Copy Number Changes in NCF1 SO HYPERTENSION LA English DT Article DE elastin; NADPH oxidase; pulse wave analysis; vascular stiffness; Williams syndrome ID SUPRAVALVULAR AORTIC-STENOSIS; PULSE-WAVE VELOCITY; CHRONIC GRANULOMATOUS-DISEASE; INCREASED ARTERIAL STIFFNESS; BLOOD-PRESSURE; BEUREN-SYNDROME; ELASTIN GENE; CARDIOVASCULAR-DISEASE; REFERENCE VALUES; SUDDEN-DEATH AB Williams syndrome is caused by the deletion of 26 to 28 genes, including elastin, on human chromosome 7. Elastin insufficiency leads to the cardiovascular hallmarks of this condition, namely focal stenosis and hypertension. Extrapolation from the Eln(+/-) mouse suggests that affected people may also have stiff vasculature, a risk factor for stroke, myocardial infarction, and cardiac death. NCF1, one of the variably deleted Williams genes, is a component of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex and is involved in the generation of oxidative stress, making it an interesting candidate modifier for vascular stiffness. Using a case-control design, vascular stiffness was evaluated by pulse wave velocity in 77 Williams cases and matched controls. Cases had stiffer conducting vessels than controls (P<0.001), with increased stiffness observed in even the youngest children with Williams syndrome. Pulse wave velocity increased with age at comparable rates in cases and controls, and although the degree of vascular stiffness varied, it was seen in both hypertensive and normotensive Williams participants. Use of antihypertensive medication and extension of the Williams deletion to include NCF1 were associated with protection from vascular stiffness. These findings demonstrate that vascular stiffness is a primary vascular phenotype in Williams syndrome and that treatment with antihypertensives or agents inhibiting oxidative stress may be important in managing patients with this condition, potentially even those who are not overtly hypertensive. C1 [Kozel, Beth A.; Danback, Joshua R.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. [Knutsen, Russell H.] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. [de las Fuentes, Lisa] Washington Univ, Sch Med, Cardiovasc Imaging & Clin Res Core Lab, Cardiovasc Div,Dept Internal Med, St Louis, MO 63110 USA. [Pober, Barbara R.] Quinnipiac Univ, Netter Sch Med, Dept Med Sci, Hamden, CT USA. [Waxler, Jessica L.; Pober, Barbara R.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Reusz, Gyorgy S.; Kis, Eva] Semmelweis Univ, Dept Pediat 1, H-1085 Budapest, Hungary. [Bhatt, Ami B.] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. [Pober, Barbara R.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Kozel, BA (reprint author), Washington Univ, Sch Med, 660 S Euclid,Campus Box 8208, St Louis, MO 63110 USA. EM Kozel_b@kids.wustl.edu OI de las Fuentes, Lisa/0000-0002-4689-325X FU Children's Discovery Institute of Washington University; St. Louis Children's Hospital; Child Health Research Center in Developmental Biology (National Institutes of Health [NIH] [K12-HD01487]; Genetic Basis of Inflammatory Airway Disease [NIH K12-HL089968]; Hungarian National Research Fund [OTKA 100909] FX Funding was provided to Dr Kozel by the Children's Discovery Institute of Washington University and St. Louis Children's Hospital. In addition, Dr Kozel received funding for the study through her appointment as a scholar of the Child Health Research Center in Developmental Biology (National Institutes of Health [NIH] K12-HD01487) and the Genetic Basis of Inflammatory Airway Disease (NIH K12-HL089968). Original pediatric control studies were supported by the Hungarian National Research Fund, OTKA 100909. NR 35 TC 5 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD JAN PY 2014 VL 63 IS 1 BP 74 EP 79 DI 10.1161/HYPERTENSIONAHA.113.02087 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 268YM UT WOS:000328206800019 PM 24126171 ER PT J AU Al Hazzouri, AZ Haan, MN Deng, YZ Neuhaus, J Yaffe, K AF Al Hazzouri, Adina Zeki Haan, Mary N. Deng, Yingzi Neuhaus, John Yaffe, Kristine TI Reduced Heart Rate Variability Is Associated With Worse Cognitive Performance in Elderly Mexican Americans SO HYPERTENSION LA English DT Article DE aging; autonomic nervous system diseases; cognition; epidemiology ID BLOOD-PRESSURE VARIABILITY; CARDIAC AUTONOMIC CONTROL; CARDIOVASCULAR RISK-FACTORS; SACRAMENTO-AREA-LATINO; MIDDLE-AGED MEN; MYOCARDIAL-INFARCTION; DIABETES-MELLITUS; ENGLISH-SPEAKING; NHANES-III; DISEASE AB Reduced heart rate variability is a strong predictor of cardiovascular risk factors, cardiovascular events, and mortality and thus may be associated with cognitive neurodegeneration. Yet, this has been relatively unexplored, particularly in minority populations with high cardiovascular burden. We used data from the Sacramento Area Latino Study on Aging to examine the cross-sectional association of reduced heart rate variability with cognitive function among elderly Mexican Americans. A total of 869 participants (mean age, 75 years; 59% women) had their 6-minute heart rate variability measured using an ECG monitor and respiration pacer in response to deep breathing. We used the mean circular resultant, known as R bar, as a measure of heart rate variability and categorized it into quartiles (Q1 to Q4 of R bar: reduced to high heart rate variability). Cognitive function was assessed using the modified Mini-Mental State Examination, a 100-point test of global cognitive function, and the Spanish and English verbal learning test, a 15-point test of verbal memory recall. In fully adjusted linear regression models, participants in quartile 1 had a 4-point lower modified Mini-Mental State Examination score (P<0.01), those in quartile 2 had a 2-point lower score (P=0.04), and those in quartile 3 had a 1-point lower score (P=0.35) compared with those in the highest quartile of R bar. Reduced R bar was not associated with verbal memory. Our results suggest that reduced heart rate variability is associated with worse performance on the test of global cognitive function, above and beyond traditional cardiovascular risk factors. C1 [Al Hazzouri, Adina Zeki; Haan, Mary N.; Neuhaus, John; Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94107 USA. [Al Hazzouri, Adina Zeki; Haan, Mary N.; Neuhaus, John; Yaffe, Kristine] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94107 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94107 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94107 USA. [Deng, Yingzi] Univ Med & Dent New Jersey, Cardiovasc Inst, Newark, NJ 07103 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. RP Al Hazzouri, AZ (reprint author), Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, 185 Berry St,Lobby 5,Suite 5700, San Francisco, CA 94107 USA. EM Adina.zekialhazzouri@ucsf.edu FU National Institute on Aging [AG12975, AG033751]; National Institute of Diabetes and Digestive and Kidney Diseases [DK60753]; American Heart Association/American Stroke Association/American Brain Foundation FX This work is supported by grants from the National Institute on Aging (AG12975, AG033751) and National Institute of Diabetes and Digestive and Kidney Diseases (DK60753). Dr Zeki Al Hazzouri is supported by the American Heart Association/American Stroke Association/American Brain Foundation Lawrence M. Brass, MD, Stroke Research Postdoctoral Fellowship. NR 44 TC 8 Z9 9 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD JAN PY 2014 VL 63 IS 1 BP 181 EP 187 DI 10.1161/HYPERTENSIONAHA.113.01888 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 268YM UT WOS:000328206800033 ER PT J AU Lamas, DJ Lederer, DJ AF Lamas, Daniela J. Lederer, David J. BE Meyer, KC Nathan, SD TI Lung Transplantation for Idiopathic Pulmonary Fibrosis SO IDIOPATHIC PULMONARY FIBROSIS: A COMPREHENSIVE CLINICAL GUIDE SE Respiratory Medicine Series LA English DT Article; Book Chapter DE Lung transplantation; Idiopathic pulmonary fibrosis; Lung allocation score; Transplant candidate selection; Deceased donor organ allocation ID BRONCHIOLITIS-OBLITERANS-SYNDROME; INTERNATIONAL GUIDELINES; ALLOGRAFT DYSFUNCTION; SURVIVAL BENEFIT; ALLOCATION SCORE; CANDIDATES; RECIPIENTS; SINGLE; DIAGNOSIS; SELECTION AB Despite advances in the development of novel pharmaceutical agents to treat idiopathic pulmonary fibrosis (IPF), there are no medical therapies known to resolve fibrosis or improve lung function in IPF. Therefore, lung transplantation remains the only life-saving therapy available to treat patients with IPF. However, a shortage of suitable donor organs limits the number of affected individuals who can undergo this procedure, and this shortage highlights the need to allocate donor lungs to those who are in the greatest need of a life-saving therapy yet ensure that those who undergo transplantation will have a reasonable expectation of long-term survival. Still, outcomes remain relatively poor for many patients after lung transplantation, although a sizable minority of patients can enjoy long-term survival after lung transplantation. C1 [Lamas, Daniela J.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Lederer, David J.] Columbia Univ, Med Ctr, Lung Transplantat Program, New York, NY 10027 USA. [Lederer, David J.] Columbia Univ, Med Ctr, Interstitial Lung Dis Program, New York, NY USA. [Lederer, David J.] Columbia Univ, Med Ctr, Div Pulm Allergy & Crit Care Med, New York, NY USA. RP Lederer, DJ (reprint author), Columbia Univ, Med Ctr, Lung Transplantat Program, New York, NY 10027 USA. EM dl427@columbia.edu NR 35 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-62703-681-8 J9 RESPIR MED SER PY 2014 VL 9 BP 363 EP 377 DI 10.1007/978-1-62703-682-5_18 D2 10.1007/978-1-62703-682-5 PG 15 WC Respiratory System SC Respiratory System GA BJH02 UT WOS:000328150500019 ER PT J AU Horning, SM Melrose, R Sultzer, D AF Horning, Sheena M. Melrose, Rebecca Sultzer, David TI Insight in Alzheimer's disease and its relation to psychiatric and behavioral disturbances SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE insight; Alzheimer's disease; dementia; apathy; depression ID NEUROBEHAVIORAL RATING-SCALE; NURSING-HOME PLACEMENT; IMPAIRED INSIGHT; DEPRESSIVE SYMPTOMS; COGNITIVE DEFICITS; APATHY; DEMENTIA; ANOSOGNOSIA; AWARENESS; RELIABILITY AB ObjectiveIndividuals suffering from Alzheimer's disease (AD) often have impaired awareness or a lack of insight into their cognitive deficits and functional abilities, especially in the later stages of the disease. Previous research has documented a relationship between depression and insight in AD, such that greater awareness of one's disease has been associated with a higher degree of depression. However, little is known about the relationship between insight, cognitive decline, and other psychiatric or behavioral problems associated with AD. MethodsThis study included 107 outpatients who met criteria for probable AD. Instruments included the Neurobehavioral Rating Scale, the Apathy Evaluation Scale, and the mini mental state exam. A series of hierarchical regression analyses were conducted to determine the relationship between insight and depressed mood, anxiety, psychosis, apathy, agitation, and behavioral retardation in AD patients after controlling for cognitive skills. ResultsInsight was found to significantly predict depressed mood, anxiety, and apathy even after controlling for global cognition. Greater insight was found to be associated with depressed mood and anxiety. However, impaired insight was associated with higher levels of apathy. ConclusionInsight may be differentially related to mood symptoms and apathy within AD, such that patients with intact insight are more depressed, whereas patients with impaired insight are more apathetic. This suggests that assessment of insight in AD may complement the clinical evaluation of depression and apathy in AD and help guide the most appropriate interventions. Published 2013. This article is a U.S. Government work and is in the public domain in the USA. C1 [Horning, Sheena M.; Melrose, Rebecca; Sultzer, David] VA Greater Los Angeles Healthcare Syst, Brain Behav & Aging Res Ctr, Los Angeles, CA USA. [Melrose, Rebecca; Sultzer, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. RP Horning, SM (reprint author), VA Greater Los Angeles Healthcare Syst, Brain Behav & Aging Res Ctr, Los Angeles, CA USA. EM Sheena.Horning@va.gov OI Horning, Sheena/0000-0002-9704-0070 FU Department of Veterans Affairs (Office of Academic Affiliation); National Institute of Mental Health [MH56031] FX This project was supported in part by the Department of Veterans Affairs (Office of Academic Affiliation, Psychology Postdoctoral Training Program to Dr. Horning, Research Career Development Award to Dr. Melrose, and Merit Review Award to Dr. Sultzer) and the National Institute of Mental Health (#MH56031). NR 43 TC 11 Z9 13 U1 1 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-6230 EI 1099-1166 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD JAN PY 2014 VL 29 IS 1 BP 77 EP 84 DI 10.1002/gps.3972 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 263QP UT WOS:000327823400008 PM 23671016 ER PT J AU Friedman, ES Calabrese, JR Ketter, TA Leon, AC Thase, ME Bowden, CL Sylvia, LG Ostracher, MJ Severe, J Iosifescu, DV Nierenberg, AA Reilly-Harrington, NA AF Friedman, E. S. Calabrese, J. R. Ketter, T. A. Leon, A. C. Thase, M. E. Bowden, C. L. Sylvia, L. G. Ostracher, M. J. Severe, J. Iosifescu, D. V. Nierenberg, A. A. Reilly-Harrington, N. A. TI Using comparative effectiveness design to improve the generalizability of bipolar treatment trials data: Contrasting LiTMUS baseline data with pre-existing placebo controlled trials SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Comparative effectiveness; Bipolar; Baseline characteristics; Generalizability ID PSYCHOTROPIC-DRUG PRESCRIPTION; LITHIUM MAINTENANCE TREATMENT; CONTROLLED 18-MONTH TRIAL; I-DISORDER; DOUBLE-BLIND; MOOD STABILIZER; ACUTE MANIA; DEPRESSION; EFFICACY; LAMOTRIGINE AB Background: Efficacy-based double-blind placebo controlled trials were conducted to establish efficacy and safety for FDA approval. Such designs allowed and encouraged the use of exclusion criteria to improve assay sensitivity and internal validity. The LiTMUS trial increased the representation of real-world individuals with bipolar disorder despite the acknowledgment that this compromises assay sensitivity. Method: To maximize generalizability, LiTMUS used broad inclusion and narrow exclusion criteria: participants experiencing mood symptoms of sufficient intensity (at least with a CGI-BP >= 3) that would warrant a change in treatment, and that lithium treatment would be a reasonable therapeutic option if they were randomized to it. At baseline demographic, illness, clinical, and treatment characteristics were collected. The LiTMUS study design and baseline sociodemographic data were compared to previous efficacy studies. Results: As compared to the previous bipolar disorder efficacy studies. LiTMUS participants were of similar age, gender, weight and illness severity; however LiTMUS participants were more racially and ethnically representative of the general population, had a greater number of mood episodes in the past 12 months, more Axis I/II comorbidity, a greater number of prior suicide attempts, and higher functional capacity. Conclusions: LiTMUS was a comparative effectiveness trial that had broad inclusion and minimal exclusion criteria that produced a more representative sample comprised of real-world participants. This design enables the results of the LiTMUS study to be a more representative of real world pharmacotherapuetic outcomes. Limitations: Limitations include possible selection bias, paucity of sociodemographic data in efficacy trials, and lack of a placebo. (C) 2013 Published by Elsevier B.V. C1 [Friedman, E. S.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Calabrese, J. R.] Case Western Reserve Univ, Univ Hosp, Case Med Ctr, Cleveland, OH 44106 USA. [Ketter, T. A.; Ostracher, M. J.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Leon, A. C.] Weill Cornell Med Coll, New York, NY USA. [Thase, M. E.] Univ Penn, Philadelphia, PA 19104 USA. [Bowden, C. L.] Univ Texas Hlth Sci, San Antonio, TX USA. [Sylvia, L. G.; Nierenberg, A. A.; Reilly-Harrington, N. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Severe, J.] NIMH, Bethesda, MD 20892 USA. [Iosifescu, D. V.] Mt Sinai Sch Med, New York, NY 10029 USA. RP Friedman, ES (reprint author), Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA. EM FriedmanE@upmc.edu OI Ostacher, Michael/0000-0003-0353-7535 FU National Institute of Mental Health [NO1MH80001] FX This study was support by a grant from the National Institute of Mental Health, Contract # NO1MH80001. NR 36 TC 2 Z9 3 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JAN PY 2014 VL 152 BP 97 EP 104 DI 10.1016/j.jad.2013.05.052 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 262UP UT WOS:000327763600013 PM 23845385 ER PT J AU Dunn, EC Solovieff, N Lowe, SR Gallagher, PJ Chaponis, J Rosand, J Koenen, KC Waters, MC Rhodes, JE Smoller, JW AF Dunn, Erin C. Solovieff, Nadia Lowe, Sarah R. Gallagher, Patience J. Chaponis, Jonathan Rosand, Jonathan Koenen, Karestan C. Waters, Mary C. Rhodes, Jean E. Smoller, Jordan W. TI Interaction between genetic variants and exposure to Hurricane Katrina on post-traumatic stress and post-traumatic growth: A prospective analysis of low income adults SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Genes; Adversity; Hurricane; Post-traumatic stress; Post-traumatic growth; Resilience ID OXYTOCIN RECEPTOR GENE; SOCIAL SUPPORT; ENVIRONMENT INTERACTION; PSYCHOLOGICAL DISTRESS; BIPOLAR DISORDER; MENTAL-ILLNESS; BDNF FUNCTION; LIFE EVENTS; DEPRESSION; RISK AB Background: There is considerable variation in psychological reactions to natural disasters, with responses ranging from relatively mild and transitory symptoms to severe and persistent posttraumatic stress (PTS). Some survivors also report post traumatic growth (PTG), or positive psychological changes due to the experience and processing of the disaster and its aftermath. Gene environment interaction (GxE) studies could offer new insight into the factors underlying variability in post disaster psychological responses. However, few studies have explored GxE in a disaster context. Methods: We examined whether Len common variants in seven genes (BDNF, CACNA1C, CRHR1, FKBP5, OXTR, RGS2, SLC6A4) modified associations between Hurricane Katrina exposure and PTS and PTG. Data were from a prospective study of 205 low-income non Hispanic Black parents residing in New Orleans prior to and following Hurricane Katrina. Results: We found a significant association (after correction) between RGS2 (rs4606; p=0.0044) and PIG, which was mainly driven by a cross over GxE=0.006), rather than a main genetic effect (p=0.071). The G (minor allele) was associated with lower PIG scores for low levels of Hurricane exposure and higher PIG scores for moderate and high levels of exposure. We also found a nominally significant association between variation in FKBP5 (rs1306780, p=0.0113) and PUG, though this result did not survive correction for multiple testing. Limitations: Although the inclusion of low-income non-Hispanic Black parents allowed us to examine GxE among a highly vulnerable group, our findings may not generalize to other populations or groups experiencing other natural disasters. Moreover, not all participants invited to participate in the genetic study provided saliva. Conclusions: To our knowledge, this is the first study to identify GxE in the context of post-traumatic growth. Future studies are needed to clarify the role of GxE in PUS and PUG and post-disaster psychological responses, especially among vulnerable populations. Published by Elsevier B.V. C1 [Dunn, Erin C.; Solovieff, Nadia; Gallagher, Patience J.; Chaponis, Jonathan; Rosand, Jonathan; Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Dunn, Erin C.; Solovieff, Nadia; Smoller, Jordan W.] Harvard Univ, Dept Psychiat, Sch Med, Cambridge, MA 02138 USA. [Lowe, Sarah R.; Koenen, Karestan C.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY 10027 USA. [Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Waters, Mary C.] Harvard Univ, Dept Sociol, Cambridge, MA 02138 USA. [Rhodes, Jean E.] Univ Massachusetts Boston, Dept Psychol, Boston, MA USA. [Smoller, Jordan W.] Harvard Univ, Ctr Dev Child, Cambridge, MA 02138 USA. RP Dunn, EC (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, 185 Cambridge St,Simches Res Bldg 6th Floor, Boston, MA 02114 USA. EM erindunn@pngu.mgh.harvard.edu RI Koenen, Karestan/K-5402-2014 OI Koenen, Karestan/0000-0003-3293-4281 FU National Center for Research Resources, National Institutes of Health [8UL1TR000170-05]; Harvard University; NIH [R01HD046162]; National Science Foundation; MacArthur Foundation; Center for Economic Policy Studies at Princeton University; Robert Wood Johnson Health and Society Program; Center on the Developing Child at Harvard University; NIMH [T32MH013043, K24MH094614]; Harvard Catalyst \ The Harvard Clinical and Translational Science Center; National Center for Advancing Translational Sciences, National Institutes of Health [8UL1TR000170-05] FX This work was conducted with support from Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 8UL1TR000170-05 and financial contributions from Harvard University and its affiliated academic health care centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Halyard Catalyst, Harvard University and its affiliated academic health care centers, or the National Institutes of Health. The larger Opening Doors Study was funded by NIH grant R01HD046162, and the National Science Foundation, the MacArthur Foundation, the Center for Economic Policy Studies at Princeton University, and the Robert Wood Johnson Health and Society Program.; Dr. Dunn was supported in part by funding from the Center on the Developing Child at Harvard University. Dr. Lowe was supported by NIMH grant T32MH013043. Dr. Smoller was funded in part by NIMH grant K24MH094614. NR 69 TC 11 Z9 11 U1 7 U2 32 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JAN PY 2014 VL 152 BP 243 EP 249 DI 10.1016/j.jad.2013.09.018 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 262UP UT WOS:000327763600032 PM 24161451 ER PT J AU Biederman, J Wozniak, J Tarko, L Serra, G Hernandez, M McDermott, K Woodsworth, KY Uchida, M Faraone, SV AF Biederman, Joseph Wozniak, Janet Tarko, Laura Serra, Giulia Hernandez, Mariely McDermott, Katie Woodsworth, K. Yvonne Uchida, Mai Faraone, Stephen V. TI Re-examining the risk for switch from unipolar to bipolar major depressive disorder in youth with ADHD: A long term prospective longitudinal controlled study SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Pediatric bipolar disorder; ADHD; Risk factors; Switch ID ATTENTION-DEFICIT HYPERACTIVITY; CHILD-BEHAVIOR CHECKLIST; FOLLOW-UP; CBCL; ADOLESCENTS; DIAGNOSIS; MANIA; PREVALENCE; PREDICTS; PARENT AB Background: Recent studies have identified subthreshold forms of bipolar (BP)-I disorder and deficits in emotional regulation as risk factors for bipolar disorder in youth. The primary aim of this study was to investigate whether emotional dysregulation and subthreshold forms of BP-I disorder increase the risk for BP switches in ADHD youth with non-bipolar MDD. Methods: We used data from two large controlled longitudinal family studies of boys and girls with and without ADHD. Subjects (N=522) were followed prospectively and blindly over an average follow up period of 11.4 years. Comparisons were made between ADHD youth with unipolar major depression (MDD) who did (N=24) and did not (N=79) switch to BP-I disorder at follow-up. Results: The rate of conversion to BP-I disorder at follow up was higher in MDD subjects with subthreshold BP-I disorder at baseline compared to those without (57% vs. 21%; OR-9.57, 95% Cl= 1.62 - 56.56, p=0.013) and in MDD subjects with deficient emotional self-regulation (OR =3.54, 95% Cl= 1.08 - 11.60, p=0.037). Limitations: The sample was largely Caucasian, so these results may not generalize to minority groups. The sample of youth with SED was small, which limited the statistical power for some analyses. Conclusions: Switches from unipolar MUD to BP-I disorder in children with ADHD and MUD were predicted by baseline subthreshold BP-I disorder symptoms and baseline deficits in emotional regulation. More work is needed to assess whether these risk factors are operant outside the context of ADHD. (C) 2013 Elsevier B.V. All rights reserved. C1 [Biederman, Joseph; Wozniak, Janet; Tarko, Laura; Serra, Giulia; Hernandez, Mariely; McDermott, Katie; Woodsworth, K. Yvonne; Uchida, Mai] Massachusetts Gen Hosp, Clin Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Biederman, Joseph; Wozniak, Janet; Tarko, Laura; Serra, Giulia; Hernandez, Mariely; McDermott, Katie; Woodsworth, K. Yvonne; Uchida, Mai] Massachusetts Gen Hosp, Clin Res Program Adult ADHD, Boston, MA 02114 USA. [Biederman, Joseph; Wozniak, Janet; Uchida, Mai] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Serra, Giulia] Univ Roma La Sapienza, NESMOS Dept, Sch Med & Psychol, St Andrea Hosp, Rome, Italy. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Clin Res Program Pediat Psychopharmacol, 55 Fruit St,YAW 6A, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NIH [R01MH050657, R01HD036317] FX This work was supported by NIH Grants R01MH050657 and R01HD036317 to Dr. Biederman. This work was also supported members of the MGH Pediatric Psychopharmacology Council. NR 29 TC 13 Z9 13 U1 2 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JAN PY 2014 VL 152 BP 347 EP 351 DI 10.1016/j.jad.2013.09.036 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 262UP UT WOS:000327763600048 PM 24144583 ER PT J AU Chen, Z Gomperts, SN Yamamoto, J Wilson, MA AF Chen, Zhe Gomperts, Stephen N. Yamamoto, Jun Wilson, Matthew A. TI Neural Representation of Spatial Topology in the Rodent Hippocampus SO NEURAL COMPUTATION LA English DT Article ID PROBABILISTIC POPULATION CODES; HIDDEN MARKOV-MODELS; PLACE CELLS; RETROSPLENIAL CORTEX; DORSAL HIPPOCAMPUS; AWAKE STATE; MEMORY; SPACE; SEQUENCES; RAT AB Pyramidal cells in the rodent hippocampus often exhibit clear spatial tuning in navigation. Although it has been long suggested that pyramidal cell activity may underlie a topological code rather than a topographic code, it remains unclear whether an abstract spatial topology can be encoded in the ensemble spiking activity of hippocampal place cells. Using a statistical approach developed previously, we investigate this question and related issues in greater detail. We recorded ensembles of hippocampal neurons as rodents freely foraged in one- and two-dimensional spatial environments and used a decode-to-uncover strategy to examine the temporally structured patterns embedded in the ensemble spiking activity in the absence of observed spatial correlates during periods of rodent navigation or awake immobility. Specifically, the spatial environment was represented by a finite discrete state space. Trajectories across spatial locations (states) were associated with consistent hippocampal ensemble spiking patterns, which were characterized by a state transition matrix. From this state transition matrix, we inferred a topology graph that defined the connectivity in the state space. In both one- and two-dimensional environments, the extracted behavior patterns from the rodent hippocampal population codes were compared against randomly shuffled spike data. In contrast to a topographic code, our results support the efficiency of topological coding in the presence of sparse sample size and fuzzy space mapping. This computational approach allows us to quantify the variability of ensemble spiking activity, examine hippocampal population codes during off-line states, and quantify the topological complexity of the environment. C1 [Chen, Zhe; Yamamoto, Jun; Wilson, Matthew A.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Chen, Zhe; Gomperts, Stephen N.; Yamamoto, Jun; Wilson, Matthew A.] MIT, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. [Gomperts, Stephen N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02116 USA. RP Chen, Z (reprint author), MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. EM zhechen@mit.edu; sgomperts@partners.org; yamajun@mit.edu; mwilson@mit.edu OI Chen, Zhe/0000-0002-6483-6056 FU NIMH NIH HHS [K08 MH081027, K08-MH081027, R01 MH061976, R01-MH061976] NR 74 TC 18 Z9 18 U1 1 U2 10 PU MIT PRESS PI CAMBRIDGE PA ONE ROGERS ST, CAMBRIDGE, MA 02142-1209 USA SN 0899-7667 EI 1530-888X J9 NEURAL COMPUT JI Neural Comput. PD JAN PY 2014 VL 26 IS 1 BP 1 EP 39 DI 10.1162/NECO_a_00538 PG 39 WC Computer Science, Artificial Intelligence; Neurosciences SC Computer Science; Neurosciences & Neurology GA 266YW UT WOS:000328061400001 PM 24102128 ER PT J AU Nomura, Y Lambertini, L Rialdi, A Lee, M Mystal, EY Grabie, M Manaster, I Huynh, N Finik, J Davey, M Davey, K Ly, J Stone, J Loudon, H Eglinton, G Hurd, Y Newcorn, JH Chen, J AF Nomura, Yoko Lambertini, Luca Rialdi, Alexander Lee, MenJean Mystal, Elana Ying Grabie, Mordy Manaster, Isaac Huynh, Nancy Finik, Jackie Davey, Mia Davey, Kei Ly, Jenny Stone, Joanne Loudon, Holly Eglinton, Gary Hurd, Yasmin Newcorn, Jeffrey H. Chen, Jia TI Global Methylation in the Placenta and Umbilical Cord Blood From Pregnancies With Maternal Gestational Diabetes, Preeclampsia, and Obesity SO REPRODUCTIVE SCIENCES LA English DT Article DE global methylation; fetal programming; placenta; umbilical cord blood; gestational diabetes mellitus; preeclampsia; obesity; birth outcomes ID DNA METHYLATION; DEVELOPMENTAL ORIGINS; IN-UTERO; MELLITUS; EXPOSURE; MOTHERS; RISK; CHILDREN; MAMMALS; DISEASE AB Emerging evidence indicates that maternal medical risk during pregnancy, such as gestational diabetes mellitus (GDM), preeclampsia, and obesity, predisposes the offspring to suboptimal development. However, the underlying biological/epigenetic mechanism in utero is still unknown. The current pilot study (N = 50) compared the levels of global methylation in the placenta and umbilical cord blood among women with and without each risk condition (GDM, preeclampsia, and obesity) and explored whether the levels of global methylation were associated with fetal/infant growth. Results show that global methylation levels in the placenta were lower in patients with gestational diabetes (P = .003) and preeclampsia (P = .05) but higher with obesity (P = .01). Suggestive negative associations were found between global methylation level in the placenta and infant body length and head circumference. While preliminary, it is possible that the placenta tissue, but not umbilical cord blood, may be epigenetically programmed by maternal GDM, preeclampsia, and obesity to carry out its own specific functions that influence fetal growth. C1 [Nomura, Yoko; Mystal, Elana Ying; Grabie, Mordy; Huynh, Nancy; Finik, Jackie; Ly, Jenny] CUNY, Queens Coll, Dept Psychol, Flushing, NY 11376 USA. [Nomura, Yoko; Mystal, Elana Ying; Grabie, Mordy; Manaster, Isaac; Huynh, Nancy; Finik, Jackie; Davey, Mia; Davey, Kei; Ly, Jenny; Hurd, Yasmin; Newcorn, Jeffrey H.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Lambertini, Luca; Rialdi, Alexander; Chen, Jia] Mt Sinai Sch Med, Dept Prevent Med, New York, NY USA. [Lambertini, Luca; Lee, MenJean] Indiana Univ, Dept Obstet & Gynecol, Indianapolis, IN 46204 USA. [Stone, Joanne; Loudon, Holly] Mt Sinai Sch Med, Dept Obstet Gynecol & Reprod Sci, New York, NY USA. [Eglinton, Gary] Cornell Univ, Weill Med Coll, Dept Obstet & Gynecol, Flushing, NY USA. [Hurd, Yasmin] James J Peters VA Med Ctr, Bronx, NY USA. [Newcorn, Jeffrey H.; Chen, Jia] Mt Sinai Sch Med, Dept Pediat, New York, NY USA. [Chen, Jia] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY USA. RP Nomura, Y (reprint author), CUNY, Queens Coll, Dept Psychol, 65-30 Kissena Blvd, Flushing, NY 11376 USA. EM Yoko.Nomura@qc.cuny.edu OI Newcorn, Jeffrey /0000-0001-8993-9337 FU National Institutes of Health (NIH) from NIMH [K01 MH080062]; NCRR [P20 RR018728]; Queens College; CUNY Research Enhancement Grant; Venture Capital Research Funding Program of the Mount Sinai Children's Environmental Health Center FX The author(s) disclosed receipt of the following financial support for the research and/or authorship of this article: the National Institutes of Health (NIH) grants from the NIMH (K01 MH080062), the NCRR (P20 RR018728), Queens College, CUNY Research Enhancement Grant, and the Venture Capital Research Funding Program of the Mount Sinai Children's Environmental Health Center. NR 33 TC 23 Z9 27 U1 1 U2 13 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD JAN PY 2014 VL 21 IS 1 BP 131 EP 137 DI 10.1177/1933719113492206 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 265CL UT WOS:000327927200014 PM 23765376 ER PT S AU Gonzalez-Otero, DM Garcia, RG Valenza, G Reyes, LM Barbieri, R AF Gonzalez-Otero, Digna M. Garcia, Ronald G. Valenza, Gaetano Reyes, Laura M. Barbieri, Riccardo BE Murray, A TI Point Process Heartbeat Dynamics Assessment of Neurocardiogenic Syncope in Children SO 2014 COMPUTING IN CARDIOLOGY CONFERENCE (CINC), VOL 41 SE Computing in Cardiology Conference LA English DT Proceedings Paper CT 41st Computing in Cardiology Conference (CinC) CY SEP 07-10, 2014 CL Cambridge, MA SP Massachusetts Inst Technol, European Soc Cardiol, IEEE EMBS, Mortara, PhysioNet, Philips, Mindray, IBM, Zoll, Mitsubishi Elect, lOP Publishing, IMES, CSAIL, Medtronic, Boston Sci, Samsung, GE ID NEURALLY-MEDIATED SYNCOPE; RATE-VARIABILITY; VASOVAGAL SYNCOPE; DOMAIN ANALYSES; TIME; SIGNALS; TILT AB The underlying mechanisms that lead to syncope are still unclear, especially in children. In this work, we applied a novel point-process model to study time-varying heartbeat dynamics and to characterize autonomic changes that occur prior to a syncopal event. Twenty-six children with history compatible with neurocardiogenic syncope (NCS) and a positive head up tilt table test (HUT) were included in the study. ECG and blood pressure signals were recorded during rest and the diagnostic HUT. Using self-developed software, a decrease of > 3 0 % of the median systolic blood pressure during HUT compared to rest was selected as the onset of the syncopal event. After ECG peak detection and correction of ectopic beats, we modeled the time between R-wave events as a history dependent inverse Gaussian (IG) and applied the point-process framework to compute several measures related with HRV. We tested for significant changes in these measures for three consecutive two-minute time intervals previous to the syncopal event. Of all measures, only the mean of the heart rate probability density function, mu(HR), and the scale parameter of the IG probability density function, xi(0)(t), presented a statistically significant increase prior to syncope, providing novel features associated with the statistical properties of heartbeat generation that could be critical to predict and explain the occurrence of syncope. C1 [Gonzalez-Otero, Digna M.; Garcia, Ronald G.; Valenza, Gaetano; Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Gonzalez-Otero, Digna M.] Univ Basque Country UPV EHU, Bilbao, Spain. [Garcia, Ronald G.] Univ Santander UDES, Sch Med, Bucaramanga, Colombia. [Valenza, Gaetano] Univ Pisa, Pisa, Italy. [Reyes, Laura M.] Univ Alberta, Edmonton, AB, Canada. RP Gonzalez-Otero, DM (reprint author), Univ Basque Country UPV EHU, Dept Commun Engn, Alameda Urquijo S-N, Bilbao 48013, Spain. EM dignamaria_gonzalez@ehu.es OI Barbieri, Riccardo/0000-0001-9381-3833; Garcia, Ronald Gerardo/0000-0002-8325-9944; Valenza, Gaetano/0000-0001-6574-1879 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 2325-887X BN 978-1-4799-4346-3 J9 COMPUT CARDIOL CONF PY 2014 VL 41 BP 77 EP 80 PG 4 WC Cardiac & Cardiovascular Systems; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology SC Cardiovascular System & Cardiology; Computer Science; Mathematical & Computational Biology GA BE2TW UT WOS:000370068300021 ER PT S AU Barbieri, R Valenza, G Citi, L Guerrisi, M Orsolini, S Tessa, C Diciotti, S Toschi, N AF Barbieri, Riccardo Valenza, Gaetano Citi, Luca Guerrisi, Maria Orsolini, Stefano Tessa, Carlo Diciotti, Stefano Toschi, Nicola BE Murray, A TI Lower Instantaneous Entropy of Heartbeat Dynamics Characterizes Cognitive Impairment in Parkinson's Disease SO 2014 COMPUTING IN CARDIOLOGY CONFERENCE (CINC), VOL 41 SE Computing in Cardiology Conference LA English DT Proceedings Paper CT 41st Computing in Cardiology Conference (CinC) CY SEP 07-10, 2014 CL Cambridge, MA SP Massachusetts Inst Technol, European Soc Cardiol, IEEE EMBS, Mortara, PhysioNet, Philips, Mindray, IBM, Zoll, Mitsubishi Elect, lOP Publishing, IMES, CSAIL, Medtronic, Boston Sci, Samsung, GE AB It has been estimated that the incidence of cognitive deficits in Parkinson's disease (PD), ranging from Mild Cognitive Impairment (MCI) to frank dementia, is six-fold compared to that in the general population. Also, PD involves postganglionic sympathetic failure and, in 25% of patients, autonomic failure. PD patients commonly present a range of ANS-dysfunction related symptoms. Since cognitive impairment has been previously linked with cardiovascular dysautonomia in PD, in this paper we investigate whether a link exists between autonomic complexity and MCI in PD. To this end, we employ our recently developed instantaneous measures of complexity, which have been explicitly designed for stochastic time series with binary events that occur in continuous time: the inhomogeneous point-process approximate and sample entropy (ipApEn and ipSampEn, respectively). Experimental results obtained by comparing 8 cognitively preserved (PD-NC) to 8 PD-MCI subjects during resting state demonstrate that grand average values of ipSampEn are able to differentiate the two groups. This suggests that a significant loss of time-varying cardiovascular complexity is associated with MCI in PD. Importantly, no other heart rate variability (HRV) measures differed significantly between groups, possibly pointing toward subtle autonomic changes (not detectable through conventional HRV analysis) which accompany the initial stage of cognitive impairment in PD. C1 [Barbieri, Riccardo; Valenza, Gaetano; Citi, Luca; Toschi, Nicola] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Valenza, Gaetano] Univ Pisa, Pisa, Italy. [Citi, Luca] Univ Essex, Colchester CO4 3SQ, Essex, England. [Guerrisi, Maria; Toschi, Nicola] Univ Roma Tor Vergata, Rome, Italy. [Orsolini, Stefano] Univ Florence, Florence, Italy. [Tessa, Carlo] Versilia Hosp, Viareggio, Italy. [Diciotti, Stefano] Univ Bologna, Alma Mater Studiorum, Cesena, 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; Barbieri, Riccardo/0000-0001-9381-3833; Diciotti, Stefano/0000-0001-8778-7819; GUERRISI, MARIA GIOVANNA/0000-0002-7456-4349; Valenza, Gaetano/0000-0001-6574-1879 NR 14 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2325-887X BN 978-1-4799-4346-3 J9 COMPUT CARDIOL CONF PY 2014 VL 41 BP 81 EP 84 PG 4 WC Cardiac & Cardiovascular Systems; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology SC Cardiovascular System & Cardiology; Computer Science; Mathematical & Computational Biology GA BE2TW UT WOS:000370068300022 ER PT S AU Randles, A Draeger, E Michor, F AF Randles, Amanda Draeger, Erik Michor, Franziska BE Murray, A TI Analysis of Pressure Gradient Across Aortic Stenosis with Massively Parallel Computational Simulations SO 2014 COMPUTING IN CARDIOLOGY CONFERENCE (CINC), VOL 41 SE Computing in Cardiology Conference LA English DT Proceedings Paper CT 41st Computing in Cardiology Conference (CinC) CY SEP 07-10, 2014 CL Cambridge, MA SP Massachusetts Inst Technol, European Soc Cardiol, IEEE EMBS, Mortara, PhysioNet, Philips, Mindray, IBM, Zoll, Mitsubishi Elect, lOP Publishing, IMES, CSAIL, Medtronic, Boston Sci, Samsung, GE AB Coarctation of the aorta (CoA) is one of the most common congenital heart defects in the United States, and despite treatment, patients have a decrease in life expectancy. Computational fluid dynamics simulations can provide the physician with a non-invasive method to measure the pressure gradient. With HARVEY, a massively parallel hemodynamics application, patient specific simulations can be conducted of large regions of the vasculature. The pressure across the stenosis is impacted by flow from nearby vessels. The purpose of this study was to study the impact of including these distal vessels in the simulation on the resulting pressure measurements. Computational fluid dynamic simulations were conducted in three subsets of one patient's vasculature. We demonstrate up to a 29% difference in calculated pressure gradient based on the number of vessels included in the simulation. These initial results are positive but need to be substantiated with further patient studies. C1 [Randles, Amanda; Draeger, Erik] Lawrence Livermore Natl Lab, Livermore, CA USA. [Randles, Amanda; Michor, Franziska] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Randles, A (reprint author), 7000 East Ave, Livermore, CA 94550 USA. EM randles2@llnl.gov NR 14 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2325-887X BN 978-1-4799-4346-3 J9 COMPUT CARDIOL CONF PY 2014 VL 41 BP 217 EP 220 PG 4 WC Cardiac & Cardiovascular Systems; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology SC Cardiovascular System & Cardiology; Computer Science; Mathematical & Computational Biology GA BE2TW UT WOS:000370068300056 ER PT S AU Valenza, G Citi, L Scilingo, EP Barbieri, R AF Valenza, Gaetano Citi, Luca Scilingo, Enzo Pasquale Barbieri, Riccardo BE Murray, A TI Assessment of Dynamic Autonomic Changes with Posture using Instantaneous Entropy Measures SO 2014 COMPUTING IN CARDIOLOGY CONFERENCE (CINC), VOL 41 SE Computing in Cardiology Conference LA English DT Proceedings Paper CT 41st Computing in Cardiology Conference (CinC) CY SEP 07-10, 2014 CL Cambridge, MA SP Massachusetts Inst Technol, European Soc Cardiol, IEEE EMBS, Mortara, PhysioNet, Philips, Mindray, IBM, Zoll, Mitsubishi Elect, lOP Publishing, IMES, CSAIL, Medtronic, Boston Sci, Samsung, GE ID HEART-RATE-VARIABILITY; APPROXIMATE ENTROPY; COMPLEXITY AB Dynamic analysis provides a poweiful methodological framework for characterizing physiological systems. In particular, complex heartbeat dynamics related to autonomic control mechanisms are known to change at each moment in time, and complexity measures have been proven to have prognostic value in both health and disease. Nevertheless, an instantaneous measure of complexity for cardiovascular time series (or any other series of stochastic physiological "events") is still missing. In this study we introduce a mathematical framework serving instantaneous complex estimates of heartbeat dynamics to characterize different activities, tasks, and/or pathological states. In particular we propose new definitions of inhomogeneous point-process approximate and sample entropy where the discrete events are modeled by probability density functions characterizing and predicting the time until the next event occurs as a function of past history. These definitions are built on our previous work employing Laguerre expansions of the Wiener-Volterra autoregressive terms to account for long-term memory. We demonstrate an exemplary study on heartbeat data gathered from healthy subjects undergoing postural changes such as stand-up, slow tilt, and fast tilt. Results show that instantaneous complexity is able to effectively track the complex autonomic changes as they are affected by different postural changes. C1 [Valenza, Gaetano; Citi, Luca; Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Valenza, Gaetano; Citi, Luca; Barbieri, Riccardo] MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Valenza, Gaetano; Scilingo, Enzo Pasquale] Univ Pisa, Res Ctr E Piaggio, I-56122 Pisa, Italy. [Citi, Luca] Univ Essex, Sch Comp Sci & Elect Engn, Colchester CO4 3SQ, Essex, England. RP Valenza, G (reprint author), Univ Pisa, Res Ctr E Piaggio, Dept Informat Engn, Via G Caruso 16, I-56122 Pisa, Italy. EM g.valenza@ieee.org OI Barbieri, Riccardo/0000-0001-9381-3833; Valenza, Gaetano/0000-0001-6574-1879 NR 16 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 978-1-4799-4346-3 J9 COMPUT CARDIOL CONF PY 2014 VL 41 BP 489 EP 492 PG 4 WC Cardiac & Cardiovascular Systems; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology SC Cardiovascular System & Cardiology; Computer Science; Mathematical & Computational Biology GA BE2TW UT WOS:000370068300124 ER PT S AU Oh, JE Cho, YW Scarcelli, G Kim, YH AF Oh, Joo-Eon Cho, Young-Wook Scarcelli, Giuliano Kim, Yoon-Ho GP IEEE TI Sub-Rayleigh Imaging via Speckle Illumination and Correlation Measurement SO 2014 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 08-13, 2014 CL San Jose, CA AB We demonstrate a sub-Rayleigh imaging technique based on speckle illumination and the second-order correlation measurement. The image resolution is related to the speckle size or the lateral coherence length of the pseudothermal light. (C) 2014 Optical Society of America C1 [Oh, Joo-Eon; Cho, Young-Wook; Kim, Yoon-Ho] Pohang Univ Sci & Technol POSTECH, Dept Phys, Pohang 790784, South Korea. [Scarcelli, Giuliano] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Scarcelli, Giuliano] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Oh, JE (reprint author), Pohang Univ Sci & Technol POSTECH, Dept Phys, Pohang 790784, South Korea. EM jooeonoh@gmail.com NR 5 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 J9 CONF LASER ELECTR PY 2014 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BE2RC UT WOS:000369908601405 ER PT S AU Sakadzic, S Mandeville, ET Gagnon, L Musacchia, JJ Yaseen, MA Yucel, MA Lefebvre, J Lesage, F Dale, AM Eikermann-Haerter, K Ayata, C Srinivasan, VJ Lo, EH Devor, A Boas, DA AF Sakadzic, Sava Mandeville, Emiri T. Gagnon, Louis Musacchia, Joseph J. Yaseen, Mohammad A. Yucel, Meryem A. Lefebvre, Joel Lesage, Frederic Dale, Anders M. Eikermann-Haerter, Katharina Ayata, Cenk Srinivasan, Vivek J. Lo, Eng H. Devor, Anna Boas, David A. GP IEEE TI High-Resolution Optical Microscopy Imaging of Cortical Oxygen Delivery and Consumption SO 2014 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 08-13, 2014 CL San Jose, CA ID BLOOD-FLOW; TISSUE; TRANSPORT; MICROCIRCULATION; VESSELS AB We applied multimodal microscopic imaging of intravascular partial pressure of O-2 (PO2) and blood flow complemented by numerical modeling to reveal the properties of the cortical microvascular oxygenation that allow uninterrupted oxygen delivery to all tissue regions in a very dynamic and energetically demanding brain. Our measurements show that at the baseline level of neuronal activity small arterioles are responsible for a significant oxygen extraction, while the most of the remaining oxygen release is taking place at the level of the first few capillary branches after precapillary arterioles. The majority of capillaries (i.e. high branching order capillaries) release little O-2 at rest and our measurements and modeling show that they act as a dynamic O-2 reserve that is recruited on demand to ensure adequate tissue oxygenation during increased neuronal activity or decrease in blood flow. These findings have potential to overturn our textbook knowledge of the capillary oxygen delivery, impact our understanding of progression of diseases that affect cerebral microcirculation, and help improving the quantitative interpretation of brain imaging modalities. C1 [Sakadzic, Sava; Gagnon, Louis; Musacchia, Joseph J.; Yaseen, Mohammad A.; Yucel, Meryem A.; Srinivasan, Vivek J.; Devor, Anna; Boas, David A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Radiol,Opt Div, MHG MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. [Mandeville, Emiri T.; Lo, Eng H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA 02129 USA. [Mandeville, Emiri T.; Lo, Eng H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Neurol, Charlestown, MA 02129 USA. [Lefebvre, Joel; Lesage, Frederic] Ecole Polytech, Dept Genie Elect, Montreal, PQ H3C 3A7, Canada. [Dale, Anders M.; Devor, Anna] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Dale, Anders M.; Devor, Anna] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Eikermann-Haerter, Katharina; Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurovasc Res Lab,Dept Radiol, Charlestown, MA 02129 USA. [Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke Serv,Dept Neurol, Charlestown, MA 02129 USA. [Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Intens Care Unit,Dept Neurol, Charlestown, MA 02129 USA. RP Sakadzic, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Radiol,Opt Div, MHG MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. EM sava@nmr.mgh.harvard.edu NR 19 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 J9 CONF LASER ELECTR PY 2014 PG 3 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BE2RC UT WOS:000369908600020 ER PT S AU Suter, MJ Hariri, LP Miller, AJ Adams, D Lanuti, M Mino-Kenudson, M AF Suter, Melissa J. Hariri, Lida P. Miller, Alyssa J. Adams, David Lanuti, Michael Mino-Kenudson, Mari GP IEEE TI Increasing the Diagnostic Yield and Accuracy of Bronchial Biopsy for the Assessment of Lung Cancer SO 2014 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 08-13, 2014 CL San Jose, CA AB Low-risk bronchoscopy techniques for retrieving biopsy samples for the diagnosis of lung cancer are hampered by low diagnostic yields, and trans-thoracic and surgical approaches carry higher intrinsic risk of complications. We are investigating the use of optical coherence tomography to increase the diagnostic yield and accuracy of bronchial biopsy. C1 [Suter, Melissa J.; Miller, Alyssa J.; Adams, David; Lanuti, Michael] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, 55 Fruit St, Boston, MA 02114 USA. [Suter, Melissa J.; Hariri, Lida P.; Miller, Alyssa J.; Adams, David] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hariri, Lida P.; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Suter, Melissa J.; Hariri, Lida P.; Lanuti, Michael; Mino-Kenudson, Mari] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Suter, MJ (reprint author), Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, 55 Fruit St, Boston, MA 02114 USA. EM msuter@partners.org NR 3 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 J9 CONF LASER ELECTR PY 2014 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BE2RC UT WOS:000369908600082 ER PT S AU Tozburun, S Siddiqui, M Vakoc, BJ AF Tozburun, Serhat Siddiqui, Meena Vakoc, Benjamin J. GP IEEE TI A 15-MHz wavelength-stepped laser based on intracavity pulse stretching and compression for optical coherence tomography SO 2014 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 08-13, 2014 CL San Jose, CA AB We introduce a wavelength-stepped laser that uses dispersive fibers in combination with a lithium-niobate modulator and a fixed Fabry-Perot etalon to achieve wavelength selection for optical-domain subsampled OCT. A 15 MHz A-scan rate is demonstrated. C1 [Tozburun, Serhat; Vakoc, Benjamin J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Tozburun, Serhat; Vakoc, Benjamin J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Siddiqui, Meena; Vakoc, Benjamin J.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Tozburun, S (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM tozburun.serhat@mgh.harvard.edu NR 5 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 J9 CONF LASER ELECTR PY 2014 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BE2RC UT WOS:000369908600103 ER PT S AU Nazem-Zadeh, MR Schwalb, JM Bagher-Ebadian, H Jafari-Khouzani, K Elisevich, KV Soltanian-Zadeh, H AF Nazem-Zadeh, Mohammad-Reza Schwalb, Jason M. Bagher-Ebadian, Hassan Jafari-Khouzani, Kourosh Elisevich, Kost V. Soltanian-Zadeh, Hamid GP IEEE TI A BAYESIAN AVERAGED RESPONSE-DRIVEN MULTINOMIAL MODEL FOR LATERALIZATION OF TEMPORAL LOBE EPILEPSY SO 2014 IEEE 11th International Symposium on Biomedical Imaging (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT 11th IEEE International Symposium on Biomedical Imaging (ISBI) CY APR 29-MAY 02, 2014 CL Beijing, PEOPLES R CHINA SP IEEE, IEEE Engn Med & Biol Soc, IEEE Signal Proc Soc, EGI, GE, Kitware DE Response-driven Lateralization Model; Temporal Lobe Epilepsy; MRI; Hippocampal volumetrics; FLAIR intensity; Bayesian model averaging ID SELECTION; SURGERY AB Purpose: To develop a Bayesian averaged multinomial model for lateralization of epileptogenicity in temporal lobe epilepsy (TLE) patients based upon features extracted from preoperative T1-weighted and FLAIR imaging. Methods: A retrospective cohort of seventy-six TLE patients with surgical outcome of Engel class I was quantitatively analyzed to extract hippocampi volumetrics and FLAIR intensity. Using multinomial logistic regression, single response-driven models were estimated. Based on Bayesian model averaging (BMA), a model was developed and its performance was compared with the single response models. Results: The Bayesian averaged model achieved a lateralization rate of 84.2% for TLE patients that was higher than any single response model. Out of the thirty-four patients who underwent phase II intracranial monitoring, the epileptogenic side was correctly lateralized in nineteen cases. Conclusion: The proposed response-driven model can improve the decision-making for surgical resection and may reduce the need for implantation of intracranial monitoring electrodes. C1 [Nazem-Zadeh, Mohammad-Reza; Bagher-Ebadian, Hassan; Jafari-Khouzani, Kourosh; Soltanian-Zadeh, Hamid] Henry Ford Hosp, Radiol & Res Adm, Detroit, MI 48202 USA. [Schwalb, Jason M.] Henry Ford Hosp, Dept Neurosurg, Detroit, MI 48202 USA. [Bagher-Ebadian, Hassan] Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA. [Jafari-Khouzani, Kourosh] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Elisevich, Kost V.] Spectrum Hlth Med Grp, Dept Clin Neurosci, Grand Rapids, MI 49503 USA. [Soltanian-Zadeh, Hamid] Univ Tehran, Sch Elect & Comp Engn, CIPCE, Tehran, Iran. RP Soltanian-Zadeh, H (reprint author), Henry Ford Hosp, Radiol & Res Adm, Detroit, MI 48202 USA. EM hamids@rad.hfh.edu FU NIH [R01EB013227] FX Special thanks to Hajar Hamidian, Abdelrahman Hassane, Oltion Meci, Harrini Vijay, and Mohammad Emari for their invaluable helps in data processing. This work was supported in part by NIH grant R01EB013227. NR 12 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4673-1961-4 J9 I S BIOMED IMAGING PY 2014 BP 197 EP 200 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BG8WQ UT WOS:000392750900050 ER PT S AU Kim, K Ye, JC Cheng, L Ying, K El Fakhri, G Li, QZ AF Kim, Kyungsang Ye, Jong Chal Cheng, Li Ying, Kui El Fakhri, Georges Li, Quanzheng GP IEEE TI TOF-PET ORDERED SUBSET RECONSTRUCTION USING NON-UNIFORM SEPARABLE QUADRATIC SURROGATES ALGORITHM SO 2014 IEEE 11th International Symposium on Biomedical Imaging (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT 11th IEEE International Symposium on Biomedical Imaging (ISBI) CY APR 29-MAY 02, 2014 CL Beijing, PEOPLES R CHINA SP IEEE, IEEE Engn Med & Biol Soc, IEEE Signal Proc Soc, EGI, GE, Kitware DE non-uniform update; separable quadratic surrogates (SQS); time of flight ID IMAGE-RECONSTRUCTION; TOMOGRAPHY AB Time of fight (TOF) PET reconstruction provides statistically improved images and converges fast. However, the convergence rates of large and small regions are often different due to the measured counts for those regions are different. In particular, signal to noise ratio (SNR) for a small region is lower than that of a large region. This results in problems that can degrade the image quality during the TOF-PET reconstruction. To address this issue, the uniform convergence is necessary to improve the quality of the reconstructed image. In this paper, we propose a TOF-PET reconstruction algorithm exploiting an ordered subset non-uniform separable quadratic surrogates (OS-NU-SQS) algorithm. Although the OS-NU-SQS algorithm has been proposed for the transmission reconstruction, each step of the OS-NU-SQS can be easily extended to the emission reconstruction. In computer simulations, we confirm that the proposed method provides more accurate images and converges uniformly compared to the TOF-based conventional ordered subset expectation maximization (OSEM). C1 [Kim, Kyungsang; El Fakhri, Georges; Li, Quanzheng] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kim, Kyungsang; El Fakhri, Georges; Li, Quanzheng] Harvard Med Sch, Boston, MA USA. [Kim, Kyungsang; Ye, Jong Chal] Korea Adv Inst Sci & Technol, Dept Bio & Brain Engn, Bio Imaging & Signal Proc Lab, Daejeon, South Korea. [Cheng, Li; Ying, Kui] Tsinghua Univ, Dept Engn Phys, Beijing, Peoples R China. RP Li, QZ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4673-1961-4 J9 I S BIOMED IMAGING PY 2014 BP 963 EP 966 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BG8WQ UT WOS:000392750900239 ER PT S AU Lee, JW Boas, DA AF Lee, Jonghwan Boas, David A. GP IEEE TI MICROSCOPIC IMAGING OF CEREBRAL BLOOD FLOW WITH OPTICAL COHERENCE TOMOGRAPHY SO 2014 IEEE 11th International Symposium on Biomedical Imaging (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT 11th IEEE International Symposium on Biomedical Imaging (ISBI) CY APR 29-MAY 02, 2014 CL Beijing, PEOPLES R CHINA SP IEEE, IEEE Engn Med & Biol Soc, IEEE Signal Proc Soc, EGI, GE, Kitware DE Optical coherence tomography; dynamic light scattering; cerebral blood flow; red blood cell; capillary flow ID VELOCITY AB This presentation will introduce three techniques that we have recently developed for microscopic imaging of cerebral blood flow (CBF) in both large vessels and capillaries. The techniques are based on optical coherence tomography (OCT). First, we integrated OCT with dynamic light scattering analysis, enabling us to measure both axial and transverse velocities at every voxel of OCT. Meanwhile, as red blood cells (RBCs) flow one by one in capillaries, the traditional decorrelation-based methods may not be suitable for quantifying the RBC flow properties of capillaries. Here, we developed another technique based on the finding that individual RBC passage can be captured in the OCT intensity signal time course. This technique enabled volumetric estimation of capillary RBC speed, flux, and density. Finally, we developed the third technique for rapid volumetric imaging of RBC flux over a capillary network, with a high temporal resolution of similar to 1 s that is essential for tracing fast hemodynamic responses. C1 [Lee, Jonghwan; Boas, David A.] Harvard Med Sch, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02115 USA. RP Lee, JW (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02115 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4673-1961-4 J9 I S BIOMED IMAGING PY 2014 BP 1401 EP 1404 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BG8WQ UT WOS:000392750900347 ER PT B AU Goldstein, AD AF Goldstein, Anatoly D. BE Joshi, J Bertino, E Thuraisingham, B Liu, L TI Reuse and Integration of Healthcare Information for Subjects in a Clinical Trial for Treatment of Recurrent Respiratory Papillomatosis SO 2014 IEEE 15TH INTERNATIONAL CONFERENCE ON INFORMATION REUSE AND INTEGRATION (IRI) LA English DT Proceedings Paper CT 15th IEEE International Conference on Information Reuse and Integration (IEEE IRI) / IRI-HI / FMI / DIM / EM-RITE / WICSOC / SocialSec / IICPC / NatSec CY AUG 13-15, 2014 CL San Francisco, CA SP IEEE Comp Soc, IEEE Syst, Man Cybernet Soc, Soc Informat Reuse Integrat, Virginia Mil Inst, Univ Pittsburgh, Sch Informat Sci DE Clinical Trial; Database for Voice Disorders; Data Integrity; Drug Trial; Healthcare Database Integration; Healthcare Data Reuse; Healthcare Information Integration; Healthcare Information Reuse AB This paper describes healthcare information reuse and integration in the clinical trial of a drug (Avastin) involving 20 research subjects diagnosed with recurrent respiratory papillomatosis (RRP) of the vocal cords and treated at Massachusetts General Hospital (MGH) Voice Center. The client/server application designed and developed by the author assisted in clinical trial data entry, storage in a relational database, retrieval, and reporting. The developed clinical trial software included data auditing to satisfy FDA requirements. Auxiliary import/export jobs were employed, which allowed to reuse standard MGH outpatient and surgical schedules and increased the efficiency of the clinical trial data management by avoiding data entry duplication. This clinical data processing design allowed the author to preserve integrity of the healthcare data used in the clinical trial. The clinical data integration allowed doctors to track the overall dynamics of the treatment process covering pre-trial, in-trial and post-trial examinations of the research subjects. C1 [Goldstein, Anatoly D.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. RP Goldstein, AD (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. EM anatoly.goldstein@mgh.harvard.edu 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 BN 978-1-4799-5879-5; 978-1-4799-5880-1 PY 2014 BP 874 EP 879 PG 6 WC Computer Science, Information Systems SC Computer Science GA BF2AL UT WOS:000380450500121 ER PT J AU Lin, TY Shah, AH AF Lin, Tsau-Young Shah, Asmi H. GP IEEE BE Lin, J Hu, XH Chang, W Nambiar, R Aggarwal, C Cercone, N Honavar, V Huan, J Mobasher, B Pyne, S TI Stochastic Finite Automata for the Translation of DNA to Protein SO 2014 IEEE INTERNATIONAL CONFERENCE ON BIG DATA (BIG DATA) LA English DT Proceedings Paper CT IEEE International Conference on Big Data CY OCT 27-30, 2014 CL Washington, DC SP IEEE, IEEE Comp Soc, ELSEVIER, Natl Sci Fdn, CISCO, CCF DE DNA; pattern; stochastic finite automata; machine learning; proteins; bigdata ID SEQUENCES AB The use of Statistical Finite Automata (SFA) has been explored in the field of understanding the DNA sequences; many focus on local patterns, namely partial representations of DNA sequences. In this paper, we focus on global and complete representations to understand the patterns in whole DNA sequences. Obviously, DNA sequences are not random. Based on Kolmogorov complexity theory, there should be some simple Turing machines that write out such sequences; here simple means the complexity of the Turing machine is simpler than the data. The primary goal of this paper is to approximate such simple Turing machines by SFA. We use SFA, via ALERGIA algorithm (in the light granular computing), to capture and analyze the translation process (DNA to protein) based on amino acids' chemical property viz., polarity. This, in turn, enables the understanding of interspecies DNA comparisons and the creation of phylogeny - the 'tree of life'. C1 [Lin, Tsau-Young; Shah, Asmi H.] San Jose State Univ, San Jose, CA 95192 USA. [Shah, Asmi H.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Shah, Asmi H.] Lets Nurture Inc, Ahmadabad, Gujarat, India. RP Lin, TY (reprint author), San Jose State Univ, San Jose, CA 95192 USA. EM tylin@cs.sjsu.edu; asmi.capri@gmail.com NR 33 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4799-5666-1 PY 2014 BP 1060 EP 1067 PG 8 WC Computer Science, Information Systems; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BF2FK UT WOS:000380462900137 ER PT J AU Bian, JG Sharp, GC Park, YK Bortfeld, T Fakhri, G AF Bian, Junguo Sharp, Gregory C. Park, Yang-kyun Bortfeld, Thomas El Fakhri, Georges GP IEEE TI Preliminary Investigation of CBCT Imaging Optimization for Image-guided Radiation Therapy SO 2014 IEEE NUCLEAR SCIENCE SYMPOSIUM AND MEDICAL IMAGING CONFERENCE (NSS/MIC) LA English DT Proceedings Paper CT IEEE Nuclear Science Symposium / Medical Imaging Conference (NSS/MIC) CY NOV 08-15, 2014 CL Seattle, WA SP IEEE ID BEAM COMPUTED-TOMOGRAPHY; PROSTATE-CANCER; PROJECTION DATA; RECONSTRUCTION; CT; RADIOTHERAPY; ALGORITHM AB Flat-panel-based cone-beam CT (CBCT) has become an important tool for Image-guided radiation therapy (IGRT). However, repeated use of CBCT imaging can result in a high accumulated radiation dose, which poses a health concern to patients. Current CBCT for IGRT also suffers from poor image quality. Thus it is important to reduce patient dose, and improve image quality of current CBCT used in IGRT. In recent years, a great deal of effort has been devoted to the development of optimization-based (i.e. iterative) image reconstruction algorithms for the purpose of reducing CBCT imaging dose or improving CBCT image quality. It has been shown that iterative reconstruction techniques may yield images of improved quality over standard analytic-based algorithms from both low-dose diagnostic CBCT data and sparse-view flat-panel-based CBCT data. However, CBCT image quality is related with both the exposure level per view and number of views at which projections are collected. It is important to explore the trade-off between the view number and exposure level for optimization-based algorithms for the purpose of both dose reduction and image quality improvement purposes. In this work, we performed a preliminary study of optimizing the CBCT imaging quality for IGRT with optimization-based reconstruction algorithms. The preliminary results show that the image quality of ASD-POCS is relatively stable across a wide range of views and exposure levels and seems to indicate that view sampling around one view per degree is more optimal than a higher sampling density with the same total exposure. C1 [Bian, Junguo; Sharp, Gregory C.; Park, Yang-kyun; Bortfeld, Thomas; El Fakhri, Georges] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Bian, Junguo; Sharp, Gregory C.; Park, Yang-kyun; Bortfeld, Thomas; El Fakhri, Georges] Harvard Med Sch, Boston, MA USA. RP Bian, JG (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4799-6097-2 PY 2014 PG 4 WC Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA BG9AN UT WOS:000392917500127 ER PT J AU Dutta, J Chelala, M Shao, XF Lorsakul, A Li, QZ El Fakhri, G AF Dutta, Joyita Chelala, Marc Shao, Xingfeng Lorsakul, Auranuch Li, Quanzheng El Fakhri, Georges GP IEEE TI Accuracy of Respiratory Motion Compensated Image Reconstruction Using 4DPET-Derived Deformation Fields SO 2014 IEEE NUCLEAR SCIENCE SYMPOSIUM AND MEDICAL IMAGING CONFERENCE (NSS/MIC) LA English DT Proceedings Paper CT IEEE Nuclear Science Symposium / Medical Imaging Conference (NSS/MIC) CY NOV 08-15, 2014 CL Seattle, WA SP IEEE ID 4-DIMENSIONAL PET AB PET quantitation in the thorax and upper abdomen is confounded by artifacts introduced by breathing motion. This has led to the emergence of a variety of techniques for motion compensated image reconstruction, many of which rely on motion information computed from a series of respiratory-gated anatomical images synchronized with the PET gates. A simpler alternative to this approach is to derive deformation fields directly from non-attenuation-corrected gated 4DPET images. The goal of this paper is to assess the accuracy of motion compensated image reconstruction based on PET-derived motion information using the ground truth and anatomically derived motion information as references. We used the Monte Carlo simulation software GATE to generate realistic PET images of the XCAT phantom with pulmonary lesions. Deformation fields were derived from 4DPET images in two passes. In the first pass, the fields were estimated from 4D non-attenuation-corrected PET images. In the second pass, 4D attenuation maps were generated using the first-pass motion estimates and then used to reconstruct 4D attenuation-corrected PET images. A second set of deformation fields were then computed from the 4D attenuation-corrected PET images. The PET-derived deformation fields were compared with the true XCAT deformations. For more realistic validation, gated pseudo-MR images were generated from the XCAT phantom. We then compared MR-derived deformation fields with the true deformations. Finally, motion compensated PET images were reconstructed using the different motion estimates, and error estimates were computed for individual organs and lesions. C1 [Dutta, Joyita; Lorsakul, Auranuch; Li, Quanzheng; El Fakhri, Georges] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. [Chelala, Marc] McGill Univ, Dept Mech Engn, Montreal, PQ H3A 0G4, Canada. [Shao, Xingfeng] Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA 90095 USA. RP Dutta, J (reprint author), Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. EM Dutta.Joyita@mgh.harvard.edu; marcchelala@gmail.com; evanshaoxf@gmail.com; lorsakul@pet.mgh.harvard.edu; Li.Quanzheng@mgh.harvard.edu; elfakhri@pet.mgh.harvard.edu FU American Lung Association Senior Research Training Fellowship; Society of Nuclear Medicine and Molecular Imaging Mitzi and William Blahd, MD, Pilot Research Grant; National Institutes of Health (NIH) [1R01EB013293, 1R01CA165221, 1R01HL110241] FX This work was supported in part by the American Lung Association Senior Research Training Fellowship, the Society of Nuclear Medicine and Molecular Imaging Mitzi and William Blahd, MD, Pilot Research Grant, and the National Institutes of Health (NIH) grants 1R01EB013293, 1R01CA165221, and 1R01HL110241. NR 9 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4799-6097-2 PY 2014 PG 4 WC Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA BG9AN UT WOS:000392917500180 ER PT J AU Lorsakul, A El Fakhri, G Ouyang, J Worstell, W Rakvongthai, Y Laine, A Li, QZ AF Lorsakul, Auranuch El Fakhri, Georges Ouyang, Jinsong Worstell, William Rakvongthai, Yothin Laine, Andrew Li, Quanzheng GP IEEE TI Numerical Observer for Objective Assessment on Carotid Plaque Using Spectral CT SO 2014 IEEE NUCLEAR SCIENCE SYMPOSIUM AND MEDICAL IMAGING CONFERENCE (NSS/MIC) LA English DT Proceedings Paper CT IEEE Nuclear Science Symposium / Medical Imaging Conference (NSS/MIC) CY NOV 08-15, 2014 CL Seattle, WA SP IEEE AB We developed a novel numerical observer with signal variability to assess feature discrimination and compare the classification performance of carotid plaque using multi-energy, dual-energy, and conventional CT images. Our numerical observer was performed in two processing steps. First, a preprocessing step accounted for each spectral image bin using Channelized Hotelling Observer with a set of Laguerre-Gaussian channels, localized prewhitening, and localized matched filtering. The intermediate score of test statistics was obtained for each spectral image bin. The scores of all the CHOs were formed as a vector. Second, in an integration step, the test statistic vectors were used to make the classification decision of plaque features using the one-dimensional Hotelling Observer with additional prewhitening and matched filtering, yielding the figure-of-merit computation. To mimic a scenario in the clinical classification task, the known statistical distribution of signal variability was included. The validation of distinguishing two different plaque features in a known background was performed on simulated images using a digital anthropomorphic phantom with known compositions of inserted carotid plaques. The comparison of the performance for the calcified-plaque and fatty-mixed-plaque identification task showed that multi-energy CT outperformed dual-energy and conventional CT systems by 153.4%-174.3% (all p < 0.01). For the differentiation task of the calcified plaque in the presence of iodinated blood, multi-energy CT yielded superior performance to the other CT systems by 158.1%-173.8% (all p < 0.01). This proposed numerical observer with signal variability is an appropriate approach for the classification performance and can be extended to other clinical tasks such as kidney or urinary stone identification applications. C1 [Lorsakul, Auranuch; El Fakhri, Georges; Ouyang, Jinsong; Rakvongthai, Yothin; Li, Quanzheng] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. [Lorsakul, Auranuch; Laine, Andrew] Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA. [El Fakhri, Georges; Ouyang, Jinsong; Li, Quanzheng] Harvard Med Sch, Dept Radiol, Boston, MA 02115 USA. [Worstell, William] PhotoDiagnost Syst Inc, Boxboro, MA 01719 USA. [Rakvongthai, Yothin] Chulalongkorn Univ, Dept Radiol, Fac Med, Bangkok 10330, Thailand. RP Lorsakul, A (reprint author), Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. EM lorsakul@pet.mgh.harvard.edu; elfakhri@pet.mgh.harvard.edu; ouyang@pet.mgh.harvard.edu; worstell@photodiagnostic.com; yothin.r@chula.ac.th; laine@columbia.edu; li.quanzheng@mgh.harvard.edu FU [R01HL110241]; [R01CA165221]; [R01EB013293] FX This work was supported in part by Grant Nos. R01HL110241, R01CA165221, and R01EB013293. NR 12 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4799-6097-2 PY 2014 PG 4 WC Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA BG9AN UT WOS:000392917500162 ER PT J AU Sabet, H El-Fakhri, G AF Sabet, Hamid El-Fakhri, Georges GP IEEE TI Novel cost-effective and high-performance modular detectors for emission tomography systems SO 2014 IEEE NUCLEAR SCIENCE SYMPOSIUM AND MEDICAL IMAGING CONFERENCE (NSS/MIC) LA English DT Proceedings Paper CT IEEE Nuclear Science Symposium / Medical Imaging Conference (NSS/MIC) CY NOV 08-15, 2014 CL Seattle, WA SP IEEE DE Cost-Effective; CsI:Tl; LYSO; High-Resolution; pixelated scintillator; laser processing; LIOB AB A major limitation of the currently available small animal PET and SPECT imaging is their relatively low sensitivity to the incident gamma rays. While providing high spatial resolution utilizing finely pitched scintillator arrays has been explored, the cost of array fabrication has been an issue. Moreover, high sensitivity has been traded off for high spatial resolution since fabrication of scintillator arrays with small pixel cross-section and large thickness can be challenging and cost-prohibitive. The currently used mechanical pixelation of scintillators results in relatively large inter-pixel gaps and hence low packing fraction and sensitivity. We control the light spread in scintillators using a novel technique called Laser-Induced Optical Barriers (LIOB). In this work we are reporting on manipulation of scintillation light spread and hence improving pixel separation in LYSO:Ce arrays fabricated by LIOB technique as well as pixelation of CsI:Tl to 0.625x0.625x5 mm(3) and 1x1x10 mm(3) pixels with 100% process yield. C1 [Sabet, Hamid; El-Fakhri, Georges] Massachusetts Gen Hosp, Harvard Med Sch, Ctr Adv Med Imaging Sci, Boston, MA 02129 USA. RP Sabet, H (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Ctr Adv Med Imaging Sci, Boston, MA 02129 USA. EM HSabet@MGH.Harvard.edu NR 2 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4799-6097-2 PY 2014 PG 3 WC Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA BG9AN UT WOS:000392917500011 ER PT J AU Verleker, AP Fang, QQ Choi, MR Clare, S Stantz, KM AF Verleker, Akshay Prabhu Fang, Qianqian Choi, Mi-Ran Clare, Susan Stantz, Keith M. GP IEEE TI An Optical Therapeutic Protocol to treat brain metastasis by mapping NIR activated drug release: A Pilot Study SO 2014 IEEE NUCLEAR SCIENCE SYMPOSIUM AND MEDICAL IMAGING CONFERENCE (NSS/MIC) LA English DT Proceedings Paper CT IEEE Nuclear Science Symposium / Medical Imaging Conference (NSS/MIC) CY NOV 08-15, 2014 CL Seattle, WA SP IEEE AB Treatment of Central Nervous System (CNS) metastasis poses a critical clinical challenge due to limitations in drug uptake across the blood brain barrier and blood-cerebrospinal fluid barrier. Recent research has shown the efficacy of using macrophages as drug carriers to target metastatic sites in the brain, which can then be activated by illuminating with near infrared radiation. The goal of this research is to develop an optically targeted therapeutic treatment of metastasis, specifically for metastatic breast cancer of the brain. As a first step towards accomplishing this, we developed a 3D Monte Carlo photon transport code capable of simulating phantoms with optical properties of brain and tumor; and validated the Monte Carlo simulated photon fluence within brain phantoms using an optical dosimetry probe. The phantom studies showed good correlation (correlation coefficient R=0.977) between the probe measurements and the Monte Carlo simulation in a white matter phantom (reduced scattering coefficient mu(1)(s) = 8.25mm(-1), absorption coefficient mu(a)=0.005 mm(-1)). Our future steps will be to implement the Monte Carlo to map out photon energy distribution in the brain, and subsequent drug release, by segmenting & translating head CT image volumes to corresponding optical properties of brain tissues. To access the therapeutic response, changes in the vascular physiology of the brain due to Her2 inhibition will be measured using dynamic contrast-enhanced imaging (e.g. DCE-CT), and with Monte Carlo based optical fluence maps. An optical treatment plan, using fast Monte Carlo software, optimized with CT segmented image volumes, would significantly reduce the treatment time and allow targeted drug activation while sparing healthy tissues. C1 [Verleker, Akshay Prabhu; Stantz, Keith M.] Purdue Univ, Sch Hlth Sci, W Lafayette, IN 47907 USA. [Fang, Qianqian] Harvard Med Sch, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Choi, Mi-Ran; Clare, Susan] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. RP Verleker, AP (reprint author), Purdue Univ, Sch Hlth Sci, W Lafayette, IN 47907 USA. EM aprabhuv@purdue.edu; fangq@nmr.mgh.harvard.edu; mi.choi@northwestern.edu; susan.clare@northwestern.edu; kstantz@purdue.edu FU DoD/BCRP Grant, "Delivery of Nano-Tethered Therapies to Brain Metastases of Primary Breast Cancer Using a Cellular Trojan Horse" FX This work was supported in part by the DoD/BCRP Grant (PI: Dr. Clare; Northwestern University), "Delivery of Nano-Tethered Therapies to Brain Metastases of Primary Breast Cancer Using a Cellular Trojan Horse". NR 17 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4799-6097-2 PY 2014 PG 3 WC Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA BG9AN UT WOS:000392917500274 ER PT J AU Wang, MD Hu, GS Guo, N El Fakhri, G Zhang, H Li, QZ AF Wang, Mengdie Hu, Guangshu Guo, Ning El Fakhri, George Zhang, Hui Li, Quanzheng GP IEEE TI A Novel Approach to the Assessment of Treatment Response Based on Gaussian Random Field SO 2014 IEEE NUCLEAR SCIENCE SYMPOSIUM AND MEDICAL IMAGING CONFERENCE (NSS/MIC) LA English DT Proceedings Paper CT IEEE Nuclear Science Symposium / Medical Imaging Conference (NSS/MIC) CY NOV 08-15, 2014 CL Seattle, WA SP IEEE ID TUMOR RESPONSE; SOLID TUMORS; PET AB Early assessment of therapeutic response is essential for clinical oncology. Many studies on therapy response involve interpretation of differences between two Positron emission tomography (PET) images, usually in terms of standardized uptake values (SUVs). However, quantitative accuracy of this measurement is limited. In this study, we propose a statistically robust way to perform therapy response evaluation based on Gaussian random field (GRF). An analytical method based on the approximate expressions of the Fisher information matrix was used to predict the variance of individual pixels of reconstructed images. Under a null hypothesis, a zero mean unit variance GRF was obtained by normalizing each pixel of the post-therapy image with the mean and standard deviation of the pre-therapy image. The receiver operating characteristic (ROC) curves and areas under the curve were computed for both the proposed method and the traditional methods using percentage change of SUVs in multiple scenarios. Results showed that the performance of therapy response assessment was significantly improved by the introduction of variance with a higher area under the curve (97.3%) than SUVmean (91.4%) and SUVmax (82.0%). C1 [Wang, Mengdie; Hu, Guangshu; Zhang, Hui] Tsinghua Univ, Dept Biomed Engn, Beijing, Peoples R China. [Guo, Ning; El Fakhri, George; Li, Quanzheng] Harvard Med Sch, Massachusetts Gen Hosp, Radiol, CAMIS, Boston, MA USA. RP Wang, MD (reprint author), Tsinghua Univ, Dept Biomed Engn, Beijing, Peoples R China. FU China Scholarship Council (CSC) [201306210270]; NIBIB [R01EB013293] FX This work was supported in part by the scholarship from China Scholarship Council (CSC, No. 201306210270) and NIBIB R01EB013293. 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 BN 978-1-4799-6097-2 PY 2014 PG 4 WC Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA BG9AN UT WOS:000392917500288 ER PT J AU Zhuang, XD Rozgic, V Crystal, M Marx, BP AF Zhuang, Xiaodan Rozgic, Viktor Crystal, Michael Marx, Brian P. GP IEEE TI IMPROVING SPEECH-BASED PTSD DETECTION VIA MULTI-VIEW LEARNING SO 2014 IEEE WORKSHOP ON SPOKEN LANGUAGE TECHNOLOGY SLT 2014 LA English DT Proceedings Paper CT IEEE Workshop on Spoken Language Technology (SLT 2014) CY DEC 07-10, 2014 CL south lake, NV SP IEEE, IEEE Signal Proc Soc DE PTSD screening; speech recognition; text classification; audio analysis; EEG signal processing; multi-view learning AB We demonstrate that by applying multi-view learning algorithms one can usefully leverage highly informative, high-cost, psychophysiological data collected in a laboratory setting, to improve PTSD screening in the field, where only less-informative, low-cost, speech data are available. Cost metrics reflect resource requirements as well as subject receptivity to data collection. The speech-based representation involves distress indicator extraction from automatic speech recognition output, and a compact holistic audio representation based on the i-vector method. A prototype PTSD screening system was developed that benefits from highly informative EEG data yet, in the field, only relies on subjects' spoken commentary in response to open ended questions. Such a system can deliver screening with significantly increased engagement, to a broader population, leading to earlier intervention and improved outcomes. Using a recent dataset collected for multi-modal computer-aided diagnosis of PTSD, we demonstrate that the proposed method significantly improves speech-based PTSD detection, without requiring costly and aversive procedures at deployment. C1 [Zhuang, Xiaodan; Rozgic, Viktor; Crystal, Michael] Raytheon BBN Technol, Speech Language & Multimedia Business Unit, Cambridge, MA 02138 USA. [Marx, Brian P.] Boston Univ, Natl Ctr PTSD, VA Boston Healthcare Syst, Sch Med, Boston, MA 02215 USA. RP Zhuang, XD (reprint author), Raytheon BBN Technol, Speech Language & Multimedia Business Unit, Cambridge, MA 02138 USA. EM xzhuang@bbn.com; vrozgic@bbn.com; mcrystal@bbn.com; brian.marx@va.gov NR 30 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4799-7129-9 PY 2014 BP 260 EP 265 PG 6 WC Computer Science, Artificial Intelligence SC Computer Science GA BF1DA UT WOS:000380375100044 ER PT J AU Iwaki, S Bonmassar, G Belliveau, JW AF Iwaki, Sunao Bonmassar, Giorgio Belliveau, John W. GP IEEE TI Visualization of human cognitive processing by MEG SO 2014 XXXITH URSI GENERAL ASSEMBLY AND SCIENTIFIC SYMPOSIUM (URSI GASS) LA English DT Proceedings Paper CT 29th URSI General Assembly and Scientific Symposium (URSI GASS) CY AUG 16-23, 2014 CL Beijing, PEOPLES R CHINA SP URSI ID CORTICAL ACTIVITY; SURFACE RECONSTRUCTION; MOTION; FMRI; PERCEPTION; DEPTH AB Each non-invasive neuroimaging technique has its own inherent limitations resulting from temporal and special inaccuracies due to the nature of information that can be measured. While functional magnetic resonance imaging (fMRI) provides excellent spatial localization of the brain activity up to sub-millimeter resolution, its temporal resolution is limited by the hemodynamic time constant. Conversely, magnetoencephalography (MEG), which measure temporal changes in neural current directly, has temporal resolution of a few milliseconds; however, its spatial accuracy is limited by the non-uniqueness of the biomagnetic inverse problem in which the spatial distribution of neural currents is estimated from the MEG field distributions outside of the head. In this paper, recent developments in multimodal neuroimaging are introduced to allow for the reconstruction of human brain dynamics with high spatial accuracy without compromising temporal resolution. Specifically, we describe a technique to combine data from MEG, MRI and fMRI to visualize human higher order visual processing while perceiving a three-dimensional (3-D) shape from two-dimensional (2-D) motion. C1 [Iwaki, Sunao] Natl Inst Adv Ind Sci & Technol, Human Technol Res Inst, Tsukuba, Ibaraki 3058566, Japan. [Bonmassar, Giorgio; Belliveau, John W.] Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. RP Iwaki, S (reprint author), Natl Inst Adv Ind Sci & Technol, Human Technol Res Inst, AIST Tsukuba Cent 6,1-1-1 Higashi, Tsukuba, Ibaraki 3058566, Japan. EM s.iwaki@aist.go.jp RI Iwaki, Sunao/B-1079-2011 OI Iwaki, Sunao/0000-0002-7123-7203 NR 16 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4673-5225-3 PY 2014 PG 4 WC Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Physics GA BE0QU UT WOS:000366628703299 ER PT J AU Cerulli, C Bossarte, RM Dichter, ME AF Cerulli, Catherine Bossarte, Robert M. Dichter, Melissa E. TI Exploring Intimate Partner Violence Status Among Male Veterans and Associated Health Outcomes SO AMERICAN JOURNAL OF MENS HEALTH LA English DT Article DE intimate partner violence; veterans; mental health; physical health ID DOMESTIC VIOLENCE; MEN; PREVALENCE; EMERGENCY; COMPUTER; VICTIMS; WOMEN AB The World Health Organization has identified intimate partner violence (IPV) as a public health issue affecting both men and women, though significantly more information is available regarding female victimization. This study examines IPV through the lens of male victimization, focusing on a comparison of physical and mental health consequences among men who are and are not military veterans. Results from a secondary analysis of data from the Behavior Risk Factor Survey taken by 13,765 males indicated that all males, regardless of veteran status, should be screened for IPV victimization given the prevalence reported in this sample (9.5% to 12.5%). Furthermore, it was found that veteran status did affect prevalence of particular health consequences, such as depression, smoking, and binge drinking. Based on the specific comparisons examined in this study, implications for Veteran's Administration Health Services are discussed, as is the need for more research on IPV victimization rates for men and the particular health consequences that they suffer. C1 [Cerulli, Catherine; Bossarte, Robert M.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Bossarte, Robert M.] Canandaigua VA Med Ctr, Canandaigua, NY USA. [Dichter, Melissa E.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Cerulli, C (reprint author), Univ Rochester, Med Ctr, Dept Psychiat, 300 Crittenden Blvd, Rochester, NY 14642 USA. EM catherine_cerulli@urmc.rochester.edu NR 25 TC 5 Z9 5 U1 3 U2 15 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1557-9883 EI 1557-9891 J9 AM J MENS HEALTH JI Am. J. Mens Health PD JAN PY 2014 VL 8 IS 1 BP 66 EP 73 DI 10.1177/1557988313492558 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 266AB UT WOS:000327992900008 PM 23832953 ER PT J AU Abedi, A Velez, MI Echevarria, KL Restrepo, MI Anzueto, A Adams, SG AF Abedi, A. Velez, M. I. Echevarria, K. L. Restrepo, M. I. Anzueto, A. Adams, S. G. TI Severe Acute Respiratory Distress Syndrome (ards) Secondary To Sirolimus-Induced Pneumonitis In A Non-Transplant Patient SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Abedi, A.; Velez, M. I.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Echevarria, K. L.; Restrepo, M. I.; Anzueto, A.; Adams, S. G.] 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 2014 VL 189 MA A2285 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838201444 ER PT J AU Ahasic, AM Tejera, P Wei, Y Su, L Mantzoros, C Thompson, BT Christiani, DC AF Ahasic, A. M. Tejera, P. Wei, Y. Su, L. Mantzoros, C. Thompson, B. T. Christiani, D. C. TI Polymorphisms In The Insulin Growth Factor Pathway, And Circulating Insulin-Like Growth Factor-1 And Insulin-Like Growth Factor Binding Protein-3 In Medical Critical Illness SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 108th International Congress of the American-Thoracic-Society CY MAY 16-21, 2014 CL San Diego, CA SP Amer Thorac Soc C1 [Ahasic, A. M.] Yale Med Sch, New Haven, CT USA. [Tejera, P.; Wei, Y.; Su, L.; Christiani, D. C.] Harvard Sch Publ Hlth, Boston, MA USA. [Mantzoros, C.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Thompson, B. T.; Christiani, D. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM amy.ahasic@yale.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 2014 VL 189 MA A1640 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838200628 ER PT J AU Ahasic, AM Su, L Mantzoros, C Thompson, BT Christiani, DC AF Ahasic, A. M. Su, L. Mantzoros, C. Thompson, B. T. Christiani, D. C. TI Predictors Of Circulating Insulin-Like Growth Factor-1 And Insulin-Like Growth Factor Binding Protein-3 In Medical Critical Illness SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 108th International Congress of the American-Thoracic-Society CY MAY 16-21, 2014 CL San Diego, CA SP Amer Thorac Soc C1 [Ahasic, A. M.] Yale Med Sch, New Haven, CT USA. [Su, L.; Christiani, D. C.] Harvard Sch Publ Hlth, Boston, MA USA. [Mantzoros, C.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Thompson, B. T.; Christiani, D. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM amy.ahasic@yale.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 2014 VL 189 MA A1641 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838200629 ER PT J AU Ahluwalia, N Lagares, D Tager, AM AF Ahluwalia, N. Lagares, D. Tager, A. M. TI Potent Fibroblast Invasion-Inducing Activity In Bleomycin-Injured Mice Is Partially Attributable To Pdgf And Partially Dependent On Fak SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Ahluwalia, N.; Lagares, D.; Tager, A. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM nahluwalia1@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 2014 VL 189 MA A1993 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838201153 ER PT J AU Akgun, KM Tate, J Pisani, MA Butt, AA Gibert, CL Fried, T Huang, L Rodriguez-Barradas, MC Rimland, D Justice, AC Crothers, KA AF Akgun, K. M. Tate, J. Pisani, M. A. Butt, A. A. Gibert, C. L. Fried, T. Huang, L. Rodriguez-Barradas, M. C. Rimland, D. Justice, A. C. Crothers, K. A. TI Hospital Readmission And Incident Skilled Nursing Facility Placement In MICU Survivors From A Nationally Representative Cohort Of Hiv-Infected And Uninfected Veterans: 1996-2010 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Akgun, K. M.; Tate, J.; Fried, T.; Justice, A. C.] Yale Univ, VA Connecticut West Haven, West Haven, CT USA. [Pisani, M. A.] Yale Univ, Sch Med, New Haven, CT USA. [Butt, A. A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Butt, A. A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Butt, A. A.] Sheikh Khalifa Med City, Abu Dhabi, U Arab Emirates. [Gibert, C. L.] VAMC, Washington, DC USA. [Gibert, C. L.] George Washington Univ, Washington, DC USA. [Huang, L.] UCSF, Div Pulm & Crit Care Med, San Francisco, CA USA. [Rodriguez-Barradas, M. C.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Rodriguez-Barradas, M. C.] Baylor Coll Med, Houston, TX 77030 USA. [Rimland, D.] Atlanta VA, Decatur, GA USA. [Rimland, D.] Emory Univ, Decatur, GA USA. [Crothers, K. A.] Univ Washington, Sch Med, Seattle, WA USA. EM kathleen.akgun@yale.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 2014 VL 189 MA A4518 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838204012 ER PT J AU Atwood, CW Kuna, ST Little, KC Hin, S Gupta, R Gurubhagavatula, I Glick, H AF Atwood, C. W. Kuna, S. T. Little, K. C. Hin, S. Gupta, R. Gurubhagavatula, I. Glick, H. TI Cost-Effectiveness Of Home Management Of Obstructive Sleep Apnea: The Veterans Sleep Apnea Treatment Trial SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Atwood, C. W.; Little, K. C.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Kuna, S. T.; Hin, S.; Gupta, R.; Gurubhagavatula, I.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Glick, H.] Univ Penn, Philadelphia, PA 19104 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 2014 VL 189 MA A3672 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838203044 ER PT J AU Beitler, JR Shaefi, S Montesi, SB Devlin, A Loring, SH Talmor, DS Malhotra, A AF Beitler, J. R. Shaefi, S. Montesi, S. B. Devlin, A. Loring, S. H. Talmor, D. S. Malhotra, A. TI Prone Positioning Reduces Mortality From Ards In The Low Tidal Volume Era: A Meta-Analysis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Beitler, J. R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Shaefi, S.; Devlin, A.; Loring, S. H.; Talmor, D. S.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Montesi, S. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Malhotra, A.] Univ Calif San Diego, La Jolla, CA 92093 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 2014 VL 189 MA A5092 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838204576 ER PT J AU Betancourt, J Kafi, A Bonet, A Shapiro, S Oh, SS Zeidler, MR AF Betancourt, J. Kafi, A. Bonet, A. Shapiro, S. Oh, S. S. Zeidler, M. R. TI Resolution Of A Mobile Right Atrial Thrombus Complicating Acute Pulmonary Embolism With Low-Dose Tissue Plasminogen Activator In A Patient With Recent Craniotomy SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Betancourt, J.; Kafi, A.; Bonet, A.; Shapiro, S.; Oh, S. S.; Zeidler, M. R.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Betancourt, J.; Kafi, A.; Bonet, A.; Shapiro, S.; Oh, S. S.; Zeidler, M. R.] West Los Angeles VA Med Ctr, Los Angeles, CA USA. EM jaimebetancourt@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 2014 VL 189 MA A6462 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838206261 ER PT J AU Birket, SE Chu, KK Fernandez, CM Tearney, GJ Rowe, SM AF Birket, S. E. Chu, K. K. Fernandez, C. M. Tearney, G. J. Rowe, S. M. TI The Relationship Between Ciliary Dynamics And Mucus Transport SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Birket, S. E.; Fernandez, C. M.; Rowe, S. M.] Univ Alabama Birmingham, Birmingham, AL USA. [Chu, K. K.; Tearney, G. 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 2014 VL 189 MA A2053 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838201213 ER PT J AU Cahalin, LP Forman, DE Manning, K Allsup, K AF Cahalin, L. P. Forman, D. E. Manning, K. Allsup, K. TI Inspiratory Muscle Testing And Training In A Patient With Heart Failure Preserved Ejection Fraction And Acute Cardiovascular Decompensation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Cahalin, L. P.] Univ Miami, Coral Gables, FL 33124 USA. [Forman, D. E.; Manning, K.; Allsup, K.] VA Boston Hlth Care Syst, Boston, MA USA. EM L.Cahalin@miami.edu 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 2014 VL 189 MA A6453 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838206252 ER PT J AU Calfee, CS Delucchi, K Parsons, PE Thompson, BT Ware, LB Matthay, MA AF Calfee, C. S. Delucchi, K. Parsons, P. E. Thompson, B. T. Ware, L. B. Matthay, M. A. CA NHLBI ARDS Network TI Latent Class Models Identify Two Endophenotypes In Ards With Differential Response To Positive End-Expiratory Pressure SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Calfee, C. S.; Delucchi, K.; Matthay, M. A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Parsons, P. E.] Univ Vermont, Burlington, VT USA. [Thompson, B. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ware, L. B.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. EM carolyn.calfee@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 2014 VL 189 MA A5090 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838204574 ER PT J AU Campbell, JD Luo, L Liu, G Juan-Guardela, B Tedrow, JR Yang, IV Correll, M Geraci, MW Quackenbush, J Sciurba, FC Schwartz, DA Kaminski, N Zhu, J Lenburg, M Beane, J Spira, A AF Campbell, J. D. Luo, L. Liu, G. Juan-Guardela, B. Tedrow, J. R. Yang, I. V. Correll, M. Geraci, M. W. Quackenbush, J. Sciurba, F. C. Schwartz, D. A. Kaminski, N. Zhu, J. Lenburg, M. Beane, J. Spira, A. TI Integrative Genetic And Gene Expression Networks Reveal Potential Roles For Microrna Isoforms In COPD And Ild SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Campbell, J. D.; Liu, G.; Lenburg, M.; Beane, J.; Spira, A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Luo, L.] Boston Univ, Med Ctr, Boston, MA USA. [Juan-Guardela, B.] Univ Pittsburgh, Pittsburgh, PA USA. [Tedrow, J. R.] Univ Pittsburgh, Simmons Ctr Interstitial Lung Dis, Pittsburgh, PA USA. [Yang, I. V.] Natl Jewish Hlth Ctr Genes Environm & Hlth, Denver, CO 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 Denver, Aurora, CO USA. [Sciurba, F. C.; Kaminski, N.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Schwartz, D. A.] Univ Colorado, Aurora, CO USA. [Zhu, J.] Icahn Sch Med Mt Sinai, New York, NY 10029 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 2014 VL 189 MA A3990 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838203344 ER PT J AU Carroll, B Dudzinski, DM Channick, RN Kabrhel, C Rosenfield, K Jaff, MR AF Carroll, B. Dudzinski, D. M. Channick, R. N. Kabrhel, C. Rosenfield, K. Jaff, M. R. TI Diagnosis Of Right Ventricular Strain In Patients With Pulmonary Embolism Is More Effective When Assessed By Echocardiography Compared To Computed Tomography SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Carroll, B.; Dudzinski, D. M.; Channick, R. N.; Kabrhel, C.; Rosenfield, K.; Jaff, M. R.] 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 2014 VL 189 MA A1861 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838201021 ER PT J AU Carroll, B Kabrhel, C Channick, RN Dudzinski, DM Jaff, MR Rosenfield, K Baker, J AF Carroll, B. Kabrhel, C. Channick, R. N. Dudzinski, D. M. Jaff, M. R. Rosenfield, K. Baker, J. TI Survival In A 45 Year Old Male With Massive Pulmonary Embolism And Cardiac Arrest With Treatment Utilizing Novel Technology After Activation Of A Multi-Disciplinary Pulmonary Embolism Response Team (pert) SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Carroll, B.; Kabrhel, C.; Channick, R. N.; Dudzinski, D. M.; Jaff, M. R.; Rosenfield, K.; Baker, 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 2014 VL 189 MA A4861 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838204353 ER PT J AU Carroll, B Kabrhel, C Baker, J Dudzinski, DM Jaff, MR McClintic, J Rosovsky, R Rosenfield, K Sundt, T Weinberg, I Channick, RN AF Carroll, B. Kabrhel, C. Baker, J. Dudzinski, D. M. Jaff, M. R. McClintic, J. Rosovsky, R. Rosenfield, K. Sundt, T. Weinberg, I. Channick, R. N. TI A Multi-Disciplinary Pulmonary Embolism Response Team (pert) For The Management Of Pulmonary Emboli: Initial Experience SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Carroll, B.; Kabrhel, C.; Baker, J.; Dudzinski, D. M.; Jaff, M. R.; McClintic, J.; Rosovsky, R.; Rosenfield, K.; Sundt, T.; Weinberg, I.; Channick, R. N.] 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 2014 VL 189 MA A1862 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838201022 ER PT J AU Causton, B Ramadas, RA Jones, K Medoff, BD AF Causton, B. Ramadas, R. A. Jones, K. Medoff, B. D. TI Carma3 Links The Innate And Adaptive Immune Response In Allergic Asthma SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Causton, B.; Ramadas, R. A.; Jones, K.; Medoff, B. D.] Harvard Med Sch, Massachusetts Gen Hosp, Charlestown, MA USA. EM bcauston@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 2014 VL 189 MA A4181 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838203535 ER PT J AU Channick, RN Delcroix, M Galie, N Ghofrani, HA Jansa, P Le Brun, FO Mehta, S 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. Jansa, P. Le Brun, F. O. Mehta, S. Perchenet, L. Pulido, T. Sastry, B. Sitbon, O. Souza, R. Torbicki, A. Rubin, L. J. Simonneau, G. TI The Effect Of Macitentan On Long-Term Outcomes In Patients With Pulmonary Arterial Hypertension By Who Functional Class: Data From The Randomized Controlled Seraphin Study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Channick, R. N.] Massachsetts Gen Hosp, Boston, MA USA. [Delcroix, M.] Univ Hosp Gasthuisberg, Leuven, Belgium. [Galie, N.] Univ Bologna, Bologna, Italy. [Ghofrani, H. A.] Univers Hosp Giessen & Marburg, German Ctr Lung Res, Giessen, Germany. [Ghofrani, H. A.] Imperial Coll London, Giessen, Germany. [Jansa, P.] Charles Univ Prague, Prague, Czech Republic. [Le Brun, F. O.; Perchenet, L.] Actel Pharmaceut Ltd, Allschwil, Switzerland. [Mehta, S.] Western Univ, London Hlth Sci Ctr, Victoria Hosp, 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 Bicetre, Le Kremlin Bicetre, France. [Souza, R.] Univ Sao Paulo, Inst Heart, Sao Paulo, Brazil. [Torbicki, A.] ECZ Otwock, Ctr Postgrad Med Educ, Otwock, Poland. [Rubin, L. J.] Univ Calif San Diego, La Jolla, CA 92093 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 2014 VL 189 MA A4783 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838204275 ER PT J AU Chen, CY Barnett, I Bajwa, E Wei, Y Wang, Z Sul, L Christiani, DC AF Chen, C. -Y. Barnett, I. Bajwa, E. Wei, Y. Wang, Z. Sul, L. Christiani, D. C. TI Genetic Regulation Of Soluble Suppression Of Tumorigenicity-2 Expression In Acute Respiratory Distress Syndrome SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Chen, C. -Y.; Barnett, I.; Wei, Y.; Wang, Z.; Sul, L.] Harvard Sch Publ Helath, Boston, MA USA. [Bajwa, E.; Christiani, D. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Christiani, D. C.] Harvard Sch Publ Hlth, Boston, MA USA. EM david.chengyu@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 2014 VL 189 MA A2781 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838202059 ER PT J AU Chen, Z Fan, V Belza, B Lee, J Borson, S Adams, SG Herting, J Kohen, R Matute-Bello, G Nguyen, HQ AF Chen, Z. Fan, V. Belza, B. Lee, J. Borson, S. Adams, S. G. Herting, J. Kohen, R. Matute-Bello, G. Nguyen, H. Q. TI Association Between Social Support And Physical Activity In Patients With COPD SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Chen, Z.; Belza, B.; Lee, J.; Borson, S.; Herting, J.; Kohen, R.] Univ Washington, Seatlle, WA USA. [Fan, V.; Matute-Bello, G.] VA Puget Sound Hlth Care Syst, HSR&D, Seattle, WA USA. [Chen, Z.; Fan, V.; Matute-Bello, G.] Univ Washington, Seattle, WA 98195 USA. [Adams, S. G.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Nguyen, H. Q.] Kaiser Permanente Southern Calif, Pasadena, CA USA. EM Huong.Q2.Nguyen@kp.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 2014 VL 189 MA A2451 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838201610 ER PT J AU Cheng, GZ Zhang, Z Ghassemi, M Silva, I Ainslie, P Celi, LA AF Cheng, G. Z. Zhang, Z. Ghassemi, M. Silva, I. Ainslie, P. Celi, L. A. TI Modeling Circadian Rhythm Variations During Sepsis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Cheng, G. Z.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zhang, Z.; Ghassemi, M.; Silva, I.; Celi, L. A.] MIT, Cambridge, MA 02139 USA. [Ainslie, P.] Univ British Columbia Okanagan, Kelowna, BC, Canada. 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 2014 VL 189 MA A3795 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838203167 ER PT J AU Cheng, GZ Townsend, K Rinehart, EM Lichtman, AH Dharmadhikari, A Divo, M Fuhlbrigge, A Goldberg, HJ AF Cheng, G. Z. Townsend, K. Rinehart, E. M. Lichtman, A. H. Dharmadhikari, A. Divo, M. Fuhlbrigge, A. Goldberg, H. J. TI A Case Of Fatal Alemtuzumab Related Diffuse Alveolar Hemorrhage SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Cheng, G. Z.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Townsend, K.; Rinehart, E. M.; Lichtman, A. H.; Dharmadhikari, A.; Divo, M.; Fuhlbrigge, A.; Goldberg, H. J.] Brigham & Women Hosp, Boston, MA USA. NR 2 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 2014 VL 189 MA A1586 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838200574 ER PT J AU Clain, J Hummel, A Specks, U Stone, J AF Clain, J. Hummel, A. Specks, U. Stone, J. CA WGET & RAVE-ITN Study Grp TI The Clinical Significance Of Antineutrophil Cytoplasmic Antibodies Of The Igm Isotype SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Clain, J.; Hummel, A.; Specks, U.] Mayo Clin, Rochester, MN USA. [Stone, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM clain.jeremy@mayo.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 2014 VL 189 MA A1468 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838200456 ER PT J AU Clark, BJ Ho, PJM Au, DH Bradley, KA Burnham, EL Moss, M AF Clark, B. J. Ho, P. -J. M. Au, D. H. Bradley, K. A. Burnham, E. L. Moss, M. CA NIH NHLBI ARDS Network TI Brief Versus Full Alcohol Use Disorders Identification Test For The Identification Of Alcohol Misuse In Critical Illness SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Clark, B. J.; Burnham, E. L.; Moss, M.] Univ Colorado Denver, Aurora, CO USA. [Ho, P. -J. M.] Denver VA Med Ctr, Denver, CO USA. [Au, D. H.] Univ Washington, VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98195 USA. [Bradley, K. A.] Grp Hlth Res Inst, Seattle, WA USA. EM brendan.clark@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 2014 VL 189 MA A5144 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838204628 ER PT J AU Clark, BJ Rubinsky, AD Ho, P Au, DH Moss, M Bradley, KA AF Clark, B. J. Rubinsky, A. D. Ho, P. Au, D. H. Moss, M. Bradley, K. A. TI Alcohol Screening Scores And Risk Of Intensive Care Unit Admission In The Veterans Affairs Health System SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Clark, B. J.; Moss, M.] Univ Colorado Denver, Aurora, CO USA. [Rubinsky, A. D.] Hlth Serv Res Dev Northwest Ctr Exellence, Seattle, WA USA. [Ho, P.] Denver VA Med Ctr, Denver, CO USA. [Au, D. H.] VA Puget Sound Hlth Care Syst, HSR&D, Seattle, WA USA. [Au, D. H.] Univ Washington, Seattle, WA 98195 USA. [Bradley, K. A.] Grp Hlth Res Inst, Seattle, WA USA. EM brendan.clark@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 2014 VL 189 MA A2179 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838201338 ER PT J AU Cloonan, SM Glass, K Bhashyam, AR Cervo, M Quackenbusch, J Mahmood, A Silverman, EK Choi, AMK AF Cloonan, S. M. Glass, K. Bhashyam, A. R. Cervo, M. Quackenbusch, J. Mahmood, A. Silverman, E. K. Choi, A. M. K. TI The COPD Susceptibility Gene Ireb2 Regulates Mitochondrial Responses To Cigarette Smoke SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Cloonan, S. M.; Choi, A. M. K.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA. [Cloonan, S. M.; Glass, K.; Quackenbusch, J.] Harvard Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA USA. [Bhashyam, A. R.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA. [Cervo, M.; Mahmood, A.; Silverman, E. K.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Cervo, M.; Mahmood, A.] Harvard Med Sch, Boston, MA USA. EM scloonan1@rics.bwh.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 2014 VL 189 MA A2994 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838202271 ER PT J AU Collins, BF Feemster, LC Uman, J Au, DH AF Collins, B. F. Feemster, L. C. Uman, J. Au, D. H. TI Obesity And Smoking Status: COPD Patient Ratings Of Quality Of Care SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Collins, B. F.; Feemster, L. C.; Uman, J.; Au, D. H.] Univ Washington, Div Pulm & Crit Care, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Uman, J.] VA Puget Sound Hlth Care Syst, Seattle, WA 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 2014 VL 189 MA A1085 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838200077 ER PT J AU Cook, AL Roche, M Ramadas, R Cho, JL Medoff, BD AF Cook, A. L. Roche, M. Ramadas, R. Cho, J. L. Medoff, B. D. TI The Role Of Carma1 In Th1 And Th2 Polarization Of T Lymphocytes SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Cook, A. L.; Roche, M.; Ramadas, R.; Cho, J. L.; Medoff, B. D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cook, A. L.] Harvard Med Sch, Boston, MA USA. NR 0 TC 0 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 2014 VL 189 MA A4182 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838203536 ER PT J AU Dada, L Sun, H Deiss-Yehiely, N Tokhtaeva, E Angulo, M Ardila, NG Garty, H Sznajder, JI Vagin, O AF Dada, L. Sun, H. Deiss-Yehiely, N. Tokhtaeva, E. Angulo, M. Ardila, N. Gabrieli Garty, H. Sznajder, J. I. Vagin, O. TI Fxyd5 Impairs Epithelial Barrier Function By Disrupting The Intercellular Interaction Between The Na,k-Atpase beta 1 Subunits SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Dada, L.; Sun, H.; Deiss-Yehiely, N.; Angulo, M.; Ardila, N. Gabrieli; Sznajder, J. I.] Northwestern Univ, Chicago, IL 60611 USA. [Tokhtaeva, E.; Vagin, O.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Dada, L.; Tokhtaeva, E.; Vagin, O.] Vet Adm Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. [Garty, H.] Weizmann Inst Sci, Rehovo, Israel. EM lauradada@northwestern.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 2014 VL 189 MA A3438 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838202714 ER PT J AU De Cruz, SJ Dzierzewski, J Martin, JL Zeidler, MR AF De Cruz, S. J. Dzierzewski, J. Martin, J. L. Zeidler, M. R. TI Improved Continuous Positive Airway Pressure Adherence Following Cognitive Behavioral Therapy SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [De Cruz, S. J.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Dzierzewski, J.; Martin, J. L.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, North Hills, CA USA. [Zeidler, M. R.] Univ Calif Los Angeles, WLA VA, Los Angeles, 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 2014 VL 189 MA A5620 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838205240 ER PT J AU DuBrock, HM LeVarge, BL Rodriguez-Lopez, JM Channick, RN AF DuBrock, H. M. LeVarge, B. L. Rodriguez-Lopez, J. M. Channick, R. N. TI An Unusual Cause Of Pulmonary Hypertension In A Young Man SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [DuBrock, H. M.; LeVarge, B. L.] Harvard Combined Program, Boston, MA USA. [Rodriguez-Lopez, J. M.; Channick, R. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM hwomble@bidmc.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 2014 VL 189 MA A4848 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838204340 ER PT J AU Fredberg, JJ Cohen, I Adam, O Yip, WK Shiner, R Peles, Z Israeli, C Calverley, PM Dagan, Y LaPrad, AS Brown, R Solway, J AF Fredberg, J. J. Cohen, I. Adam, O. Yip, W. -K. Shiner, R. Peles, Z. Israeli, C. Calverley, P. M. Dagan, Y. LaPrad, A. S. Brown, R. Solway, J. TI Determination Of Total Lung Capacity (tlc) Without Body Plethysmography SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Fredberg, J. J.; Yip, W. -K.] Harvard Sch Publ Hlth, Boston, MA USA. [Cohen, I.; Adam, O.; Peles, Z.; Israeli, C.; Dagan, Y.; LaPrad, A. S.] PulmOne Adv Med Devices Ltd, Raanana, Israel. [Shiner, R.] Imperial Coll, London, England. [Calverley, P. M.] Univ Liverpool, Liverpool, Merseyside, England. [Brown, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Solway, J.] Univ Chicago, Chicago, IL 60637 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 2014 VL 189 MA A2933 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838202210 ER PT J AU Garshick, E Hart, JE Morse, LR DeVivo, I AF Garshick, E. Hart, J. E. Morse, L. R. DeVivo, I. TI Predictors Of Telomere Length In Chronic Spinal Cord Injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Garshick, E.] VA Boston Healthcare Syst, West Roxbury, MA USA. [Hart, J. E.; DeVivo, I.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Morse, L. R.] Spaulding Rehabil Hosp, Boston, MA USA. EM eric.garshick@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 2014 VL 189 MA A3886 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838203258 ER PT J AU Gazourian, L Spring, LM Meserve, EK Jagannathan, JP Bhatt, AS Weinhouse, GL Pinto-Plata, VM Soiffer, RJ Antin, JH Ho, VT Baron, RM Sholl, LM Washko, GR AF Gazourian, L. Spring, L. M. Meserve, E. K. Jagannathan, J. P. Bhatt, A. S. Weinhouse, G. L. Pinto-Plata, V. M. Soiffer, R. J. Antin, J. H. Ho, V. T. Baron, R. M. Sholl, L. M. Washko, G. R. TI Pulmonary Clinicopathological Correlation In Long Term Survivors Following Allogeneic Hematopoietic Stem Cell Transplantation: An Autopsy Series SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Gazourian, L.; Spring, L. M.; Meserve, E. K.; Weinhouse, G. L.; Pinto-Plata, V. M.; Baron, R. M.; Sholl, L. M.; Washko, G. R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Jagannathan, J. P.; Bhatt, A. S.; Soiffer, R. J.; Antin, J. H.; Ho, V. T.] Dana Farber Canc Inst, Boston, MA 02115 USA. EM lgazourian@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 2014 VL 189 MA A3263 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838202539 ER PT J AU Gilpin, SE Ren, X Wu, T Guyette, JP Mathisen, DJ Vacanti, JP Ott, H AF Gilpin, S. E. Ren, X. Wu, T. Guyette, J. P. Mathisen, D. J. Vacanti, J. P. Ott, H. TI Whole Organ Culture And Re-Seeding Of Decellularized Human Lungs SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Gilpin, S. E.; Ren, X.; Wu, T.; Guyette, J. P.; Mathisen, D. J.; Vacanti, J. P.; Ott, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM sgilpin@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 2014 VL 189 MA A2656 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838201814 ER PT J AU Gladysheva, E Kelly, VJ Kone, M Venegas, JG Melo, MFV Musch, G Winkler, T Greenblatt, EE Hibbert, KA Kohli, P Rodriguez-Lopez, J Channick, RN Harris, RS AF Gladysheva, E. Kelly, V. J. Kone, M. Venegas, J. G. Melo, M. F. Vidal Musch, G. Winkler, T. Greenblatt, E. E. Hibbert, K. A. Kohli, P. Rodriguez-Lopez, J. Channick, R. N. Harris, R. S. TI Evaluation Of Pulmonary Perfusion Heterogeneity And Vascular Compliance In Patients With Pulmonary Arterial Hypertension Using Functional Pet Imaging SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Gladysheva, E.; Kelly, V. J.; Kone, M.; Venegas, J. G.; Melo, M. F. Vidal; Musch, G.; Winkler, T.; Greenblatt, E. E.; Hibbert, K. A.; Kohli, P.; Rodriguez-Lopez, J.; Channick, R. N.; Harris, R. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Venegas, J. G.; Melo, M. F. Vidal; Musch, G.; Harris, R. S.] Harvard Med Sch, Boston, MA USA. [Winkler, T.; Greenblatt, E. E.] MIT, 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 2014 VL 189 MA A4725 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838204217 ER PT J AU Golnabi, AH Harris, RS Venegas, JG Winkler, T AF Golnabi, A. H. Harris, R. S. Venegas, J. G. Winkler, T. TI Can High Tidal Volumes Prevent Severe Bronchoconstriction And Ventilation Defects? SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Golnabi, A. H.; Harris, R. S.; Venegas, J. G.; Winkler, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Golnabi, A. H.; Harris, R. S.; Venegas, J. G.; Winkler, T.] 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 2014 VL 189 MA A2686 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838201844 ER PT J AU Greenblatt, EE Alcoforado, L De Andrade, AD Venegas, JG AF Greenblatt, E. E. Alcoforado, L. Dornelas De Andrade, A. Venegas, J. G. TI Using Average Anatomical Information To Analyze Scintigraphy Images Of Aerosol Deposition SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Greenblatt, E. E.; Venegas, J. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Greenblatt, E. E.] MIT, Boston, MA USA. [Alcoforado, L.; Dornelas De Andrade, A.] Univ Fed Pernambuco, Recife, PE, Brazil. [Venegas, J. G.] Harvard Med Sch, Boston, MA USA. 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 2014 VL 189 MA A4978 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838204470 ER PT J AU Greenblatt, EE Venegas, JG AF Greenblatt, E. E. Venegas, J. G. TI Estimating Ventilation From Injected Nn13 With Delayed Tracer Arrival SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Greenblatt, E. E.; Venegas, J. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Greenblatt, E. E.] MIT, Boston, MA USA. [Greenblatt, E. E.; Venegas, J. G.] Harvard Med Sch, Boston, MA USA. 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 2014 VL 189 MA A4315 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838203669 ER PT J AU Gupta, P Tang, X Gossett, JM Gall, CM Lauer, C Rice, TB Carroll, CL Kacmarek, R Wetzel, RC AF Gupta, P. Tang, X. Gossett, J. M. Gall, C. M. Lauer, C. Rice, T. B. Carroll, C. L. Kacmarek, R. Wetzel, R. C. TI Association Of Center Volume With Outcomes In Critically Ill Children With Acute Asthma: A Multicenter Analysis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Gupta, P.; Tang, X.; Gossett, J. M.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Gall, C. M.; Lauer, C.; Rice, T. B.] VPS LLC, Brookfield, WI USA. [Carroll, C. L.] Connecticut Childrens Med Ctr, Hartford, CT USA. [Kacmarek, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wetzel, R. C.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. EM pgupta2@uams.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 2014 VL 189 MA A2300 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838201459 ER PT J AU Hardin, CC Dang, Q Manomohan, G Tian, X Dubrovskyi, O Tambe, DT Butler, JP Birukov, KG Fredberg, JJ Krishnan, R AF Hardin, C. C. Dang, Q. Manomohan, G. Tian, X. Dubrovskyi, O. Tambe, D. T. Butler, J. P. Birukov, K. G. Fredberg, J. J. Krishnan, R. TI Stress Redistribution Within Endothelial Monolayers During Thrombin-Induced Gap Formation 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. [Dang, Q.; Manomohan, G.; Krishnan, R.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Tian, X.; Dubrovskyi, O.; Birukov, K. G.] Univ Chicago, Chicago, IL 60637 USA. [Tambe, D. T.; Butler, J. P.; Fredberg, J. J.] Harvard Sch Publ Hlth, Boston, MA USA. EM chardin@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 2014 VL 189 MA A5326 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838204810 ER PT J AU Hariri, LP Mino-Kenudson, M Lanuti, M Miller, AJ Suter, MJ AF Hariri, L. P. Mino-Kenudson, M. Lanuti, M. Miller, A. J. Suter, M. J. TI Diagnosis Of Primary Lung Carcinomas Using Optical Coherence Tomography SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Hariri, L. P.; Mino-Kenudson, M.; Lanuti, M.; Miller, A. J.; Suter, M. 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 2014 VL 189 MA A3576 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838202851 ER PT J AU Hibbert, KA Winkler, T Kelly, VJ Melo, MFV Harris, RS Wellman, TJ Falcao, LR Szabari, MV Venegas, JG Musch, G AF Hibbert, K. A. Winkler, T. Kelly, V. J. Melo, M. F. Vidal Harris, R. S. Wellman, T. J. Falcao, L. R. Szabari, M. V. Venegas, J. G. Musch, G. TI V/q And Ventilation Heterogeneity In A Sheep Model Of Ards SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Hibbert, K. A.; Winkler, T.; Kelly, V. J.; Melo, M. F. Vidal; Harris, R. S.; Falcao, L. R.; Szabari, M. V.; Venegas, J. G.; Musch, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hibbert, K. A.; Winkler, T.; Kelly, V. J.; Melo, M. F. Vidal; Harris, R. S.; Falcao, L. R.; Szabari, M. V.; 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 2014 VL 189 MA A5019 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838204511 ER PT J AU Joo, MJ Au, DH Fitzgibbon, M Bunyan, A Vinicky, M Lee, TA AF Joo, M. J. Au, D. H. Fitzgibbon, M. Bunyan, A. Vinicky, M. Lee, T. A. TI Comparative Effectiveness Of A COPD Assessment And Management Bundle Versus Usual Care: Baseline Characteristics SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Joo, M. J.; Fitzgibbon, M.; Bunyan, A.; Vinicky, M.; Lee, T. A.] Univ Illinois, Chicago, IL USA. [Au, D. H.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. EM joo@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 2014 VL 189 MA A3030 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838202307 ER PT J AU Kelly, VJ Winkler, T Kone, M Hamilos, DL Greenblatt, EE Hibbert, KA Gladysheva, ES Costa, LD Venegas, JG Harris, RS AF Kelly, V. J. Winkler, T. Kone, M. Hamilos, D. L. Greenblatt, E. E. Hibbert, K. A. Gladysheva, E. S. Costa, L. Degani Venegas, J. G. Harris, R. S. TI Who Moved My Perfusion? The Early And Late Phase Pulmonary Response To Whole Lung Allergen Challenge SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Kelly, V. J.; Winkler, T.; Kone, M.; Hamilos, D. L.; Greenblatt, E. E.; Hibbert, K. A.; Gladysheva, E. S.; Costa, L. Degani; Venegas, J. G.; Harris, R. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kelly, V. J.; Winkler, T.; Hamilos, D. L.; Hibbert, K. A.; Gladysheva, E. S.; Costa, L. Degani; Venegas, J. G.; Harris, R. S.] Harvard Med Sch, Boston, MA USA. [Greenblatt, E. E.] MIT, Boston, MA USA. EM vjkelly@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 2014 VL 189 MA A2685 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838201843 ER PT J AU Keriwala, R Wheeler, A Thompson, BT Rice, TW AF Keriwala, R. Wheeler, A. Thompson, B. T. Rice, T. W. CA NIH NHLBI ARDS Network TI Vasopressor Utilization In Acute Respiratory Distress Syndrome (ards) Network Studies SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 108th International Congress of the American-Thoracic-Society CY MAY 16-21, 2014 CL San Diego, CA SP Amer Thorac Soc C1 [Keriwala, R.; Wheeler, A.; Rice, T. W.] Vanderbilt Univ, Nashville, TN 37235 USA. [Thompson, B. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM raj.keriwala@vanderbilt.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 2014 VL 189 MA A1630 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838200618 ER PT J AU Knipe, RS Liao, JK Tager, AM AF Knipe, R. S. Liao, J. K. Tager, A. M. TI Both Rock Isoforms, Rock1 And Rock2, Are Independently Required For The Development Of Pulmonary Fibrosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Knipe, R. S.; Tager, A. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Liao, J. K.] Univ Chicago, Chicago, IL 60637 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 2014 VL 189 MA A1951 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838201111 ER PT J AU Kohli, P Neilan, T Natarajan, P Kwong, R Malhotra, A Celli, BR Harris, RS AF Kohli, P. Neilan, T. Natarajan, P. Kwong, R. Malhotra, A. Celli, B. R. Harris, R. S. TI Hyperinflation: A Potential Effect Modifier Of Cardiovascular Performance In Individuals With COPD And Heart Disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Kohli, P.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Neilan, T.] Massachusetts Gen Hosp, Dept Med, Div Radiol, Div Cardiol,Cardiac MR PET CT Program, Boston, MA 02114 USA. [Natarajan, P.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Kwong, R.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Malhotra, A.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Celli, B. R.] Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA. EM pkohli@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 2014 VL 189 MA A1125 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838200116 ER PT J AU Kradin, RL Channick, RN Kovach, A Wright, C AF Kradin, R. L. Channick, R. N. Kovach, A. Wright, C. TI Thromboendarterectomy In The Treatment Of Chronic Thromboemebolic Disorder: A Clinicopathological Study Of 42 Patients At The Massachusetts General Hospital From 2010-2013 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Kradin, R. L.; Channick, R. N.; Kovach, A.; Wright, 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 2014 VL 189 MA A1841 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838201001 ER PT J AU Lagares, D Ghassemi-Kakroodi, P Tremblay, C Baron, M Blati, M Zhan, Y Pelletier, JP Martel-Pelletier, J Tager, AM Kapoor, M AF Lagares, D. Ghassemi-Kakroodi, P. Tremblay, C. Baron, M. Blati, M. Zhan, Y. Pelletier, J-Pierre Martel-Pelletier, J. Tager, A. M. Kapoor, M. TI Fibroblast-Derived Ephrin-B2 Regulates Lung Fibrosis In Vivo By Promoting Fibroblast Recruitment And Myofibroblast Differentiation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Lagares, D.; Tager, A. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ghassemi-Kakroodi, P.; Tremblay, C.; Baron, M.; Blati, M.; Zhan, Y.; Pelletier, J-Pierre; Martel-Pelletier, J.; Kapoor, M.] Univ Montreal, Dept Med, Montreal, PQ, Canada. EM dlagares@mgh.harvard.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 2014 VL 189 MA A1242 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838200232 ER PT J AU Lai, PS Hang, JQ Zhang, FY Zheng, BY Valeri, L Eisen, EA Christiani, DC AF Lai, P. S. Hang, J. -Q. Zhang, F. -Y. Zheng, B. -Y. Valeri, L. Eisen, E. A. Christiani, D. C. TI Function Improvement Is Sustained After Work Cessation 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 02114 USA. [Hang, J. -Q.; Zhang, F. -Y.; Zheng, B. -Y.] Shanghai Putuo Peoples Hosp, Shanghai, Peoples R China. [Valeri, L.] Harvard Sch Publ Hlth, Boston, MA USA. [Eisen, E. A.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Christiani, D. C.] Harvard Sch Publ Hlth, Boston, MA USA. 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 2014 VL 189 MA A6502 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838206301 ER PT J AU Lai, PS Hang, JQ Zhang, FY Sun, J Zheng, BY Washko, GR Christiani, DC AF Lai, P. S. Hang, J. -Q. Zhang, F. -Y. Sun, J. Zheng, B. -Y. Washko, G. R. Christiani, D. C. TI Gender Differences In Body Composition Associated With Occupational Endotoxin Exposure SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Lai, P. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hang, J. -Q.; Zhang, F. -Y.; Sun, J.; Zheng, B. -Y.] Shanghai Putuo Peoples Hosp, Shanghai, Peoples R China. [Washko, G. R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Christiani, D. C.] Harvard Sch Publ Hlth, Boston, MA USA. 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 2014 VL 189 MA A5223 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838204707 ER PT J AU Lai, PS Sheehan, WJ Petty, CR Coull, B Christiani, DC Gold, DR Phipatanakul, W AF Lai, P. S. Sheehan, W. J. Petty, C. R. Coull, B. Christiani, D. C. Gold, D. R. Phipatanakul, W. TI School Endotoxin Exposure Is Associated With Increased Asthma Morbidity SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Lai, P. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sheehan, W. J.; Petty, C. R.; Phipatanakul, W.] Childrens Hosp Boston, Boston, MA USA. [Coull, B.; Christiani, D. C.; Gold, D. R.] Harvard Sch Publ Hlth, Boston, MA USA. 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 2014 VL 189 MA A2288 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838201447 ER PT J AU Lai, PS Hang, JQ Zhang, FY Sun, J Zheng, BY Washko, GR Christiani, DC AF Lai, P. S. Hang, J. -Q. Zhang, F. -Y. Sun, J. Zheng, B. -Y. Washko, G. R. Christiani, D. C. TI Cotton Textile Work Is Associated With Persistent Changes In Lung Density On Quantitative CT Scans SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Lai, P. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hang, J. -Q.; Zhang, F. -Y.; Sun, J.; Zheng, B. -Y.] Shanghai Putuo Peoples Hosp, Shanghai, Peoples R China. [Washko, G. R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Christiani, D. C.] Harvard Sch Publ Hlth, Boston, MA USA. EM plai@partners.org 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 2014 VL 189 MA A5104 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838204588 ER PT J AU Lim, SR Ruhrmund, DW Arfsten, AE Dolim, K Qin, X Buckman, BO Shea, BS Tager, AM Seiwert, SD Kossen, K AF Lim, S. R. Ruhrmund, D. W. Arfsten, A. E. Dolim, K. Qin, X. Buckman, B. O. Shea, B. S. Tager, A. M. Seiwert, S. D. Kossen, K. TI Impact Of Lpa And Lpa1 Receptor Antagonists On Gene And Protein Expression In Human Primary Cells SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Lim, S. R.; Ruhrmund, D. W.; Arfsten, A. E.; Dolim, K.; Qin, X.; Buckman, B. O.; Seiwert, S. D.; Kossen, K.] InterMune Inc, Brisbane, CA USA. [Shea, B. S.; Tager, A. M.] 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 2014 VL 189 MA A2016 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838201176 ER PT J AU Lv, N Xiao, L Camargo, CA Wilson, SR Strub, P Buist, S Nadeau, KC Lavori, P Ma, J AF Lv, N. Xiao, L. Camargo, C. A. Wilson, S. R. Strub, P. Buist, S. Nadeau, K. C. Lavori, P. Ma, J. TI Abdominal And General Obesity, Sleep Disturbance, And Level Of Control In Adults With Uncontrolled Asthma SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Lv, N.; Xiao, L.; Wilson, S. R.; Ma, J.] Palo Alto Med Fdn, Res Inst, Palo Alto, CA 94301 USA. [Camargo, C. A.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Strub, P.] San Francisco Med Ctr, Permanente Med Grp, San Francisco, CA USA. [Buist, S.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Nadeau, K. C.] Stanford Univ, Stanford, CA 94305 USA. [Lavori, P.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. EM lvn@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 2014 VL 189 MA A5380 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838205007 ER PT J AU Mansell, DM Iqbal, S Teach, SJ Camargo, CA Wang, Z Pillai, DK Gordish-Dressman, H Maltz, L Wiles, A Payne, AS Prosper, D Nwachukwu, F Tsegaye, Y Certner, N Lazaroff, R Mubeen, H Jiggetts, J Behniwal, S Dave, R Marwah, R Mejia, M Freishtat, RJ AF Mansell, D. M. Iqbal, S. Teach, S. J. Camargo, C. A. Wang, Z. Pillai, D. K. Gordish-Dressman, H. Maltz, L. Wiles, A. Payne, A. S. Prosper, D. Nwachukwu, F. Tsegaye, Y. Certner, N. Lazaroff, R. Mubeen, H. Jiggetts, J. Behniwal, S. Dave, R. Marwah, R. Mejia, M. Freishtat, R. J. TI Vitamin D And Glucocorticoids Interact To Reduce Ubiquitin C In Asthmatic Epithelium SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Mansell, D. M.] Howard Univ, Washington, DC 20059 USA. [Iqbal, S.; Teach, S. J.; Wang, Z.; Pillai, D. K.; Gordish-Dressman, H.; Maltz, L.; Wiles, A.; Payne, A. S.; Prosper, D.; Nwachukwu, F.; Tsegaye, Y.; Certner, N.; Lazaroff, R.; Mubeen, H.; Jiggetts, J.; Behniwal, S.; Dave, R.; Marwah, R.; Mejia, M.; Freishtat, R. J.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Camargo, C. A.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. EM douglas.m.mansell@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 2014 VL 189 MA A4880 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838204372 ER PT J AU Martinez, CH Moy, ML Nguyen, HQ Cohen, MD Kadri, R Roman, P Holleman, RG Kim, HM Goodrich, DE Giardino, ND Richardson, CR AF Martinez, C. H. Moy, M. L. Nguyen, H. Q. Cohen, M. D. Kadri, R. Roman, P. Holleman, R. G. Kim, H. M. Goodrich, D. E. Giardino, N. D. Richardson, C. R. TI Internet-Mediated Recruitment Of Rural Veterans In A Randomized Controlled Trial Of A Walking Program For COPD SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Martinez, C. H.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Moy, M. L.] Harvard Med Sch, VA Boston Healthcare Syst, Boston, MA USA. [Nguyen, H. Q.] Kaiser Permanente Southern Calif, Pasadena, CA USA. [Cohen, M. D.] VA New York Harbor Hlth Care Serv, Brooklyn, NY USA. [Kadri, R.; Roman, P.; Holleman, R. G.; Goodrich, D. E.] VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Kim, H. M.; Giardino, N. D.; Richardson, C. R.] Univ Michigan, Ann Arbor, MI 48109 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 2014 VL 189 MA A5362 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838204846 ER PT J AU Martinez, CH Moy, ML Nguyen, HQ Cohen, M Kadri, R Roman, P Holleman, RG Kim, HM Goodrich, DE Giardino, ND Richardson, CR AF Martinez, C. H. Moy, M. L. Nguyen, H. Q. Cohen, M. Kadri, R. Roman, P. Holleman, R. G. Kim, H. M. Goodrich, D. E. Giardino, N. D. Richardson, C. R. TI Beliefs About Disease Controllability Are Related With Baseline Physical Activity And With Longitudinal Change On Physical Activity Among COPD Patients SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Martinez, C. H.; Richardson, C. R.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Martinez, C. H.; Moy, M. L.] Harvard Med Sch, VA Boston Healthcare Syst, Boston, MA USA. [Nguyen, H. Q.] Kaiser Permanente Southern Calif, Pasadena, CA USA. [Cohen, M.] VA New York Harbor, Brooklyn, NY USA. [Kadri, R.; Roman, P.; Holleman, R. G.; Goodrich, D. E.] VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Kim, H. M.; Giardino, N. D.] Univ Michigan, Ann Arbor, MI 48109 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 2014 VL 189 MA A4026 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838203380 ER PT J AU Martires, JS Girgis, GM Chen, J Hoo, GWS AF Martires, J. S. Girgis, G. M. Chen, J. Hoo, G. W. Soo TI Mycobacterium Xenopi Pleural Infection: Role Of Fdg-Pet Scan In Diagnosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 108th International Congress of the American-Thoracic-Society CY MAY 16-21, 2014 CL San Diego, CA SP Amer Thorac Soc C1 [Martires, J. S.; Girgis, G. M.; Chen, J.; Hoo, G. W. Soo] VA Greater Los Angeles Healthcare Syst, West Los Angeles Vet Affairs Med Ctr, Los Angeles, 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 2014 VL 189 MA A1742 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838200730 ER PT J AU Matura, L McDonough, A Hanlon, AL Carroll, DL AF Matura, L. McDonough, A. Hanlon, A. L. Carroll, D. L. TI Measuring Symptom Severity In Pulmonary Arterial Hypertension SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Matura, L.; Hanlon, A. L.] Univ Penn, Philadelphia, PA 19104 USA. [McDonough, A.] Univ Massachusetts, Boston, MA 02125 USA. [Carroll, D. L.] 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 2014 VL 189 MA A2454 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838201613 ER PT J AU Matura, L McDonough, A Hanlon, AL Carroll, DL AF Matura, L. McDonough, A. Hanlon, A. L. Carroll, D. L. TI Validity And Reliability Of The Pulmonary Arterial Hypertension Symptom Burden Scale SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 108th International Congress of the American-Thoracic-Society CY MAY 16-21, 2014 CL San Diego, CA SP Amer Thorac Soc C1 [Matura, L.; Hanlon, A. L.] Univ Penn, Philadelphia, PA 19104 USA. [McDonough, A.] Univ Massachusetts, Lowell, MA USA. [Carroll, D. L.] 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 2014 VL 189 MA A1790 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838200778 ER PT J AU McCarthy, CM Blum, L Cobb, JP Camargo, CA Quraishi, SA AF McCarthy, C. M. Blum, L. Cobb, J. P. Camargo, C. A. Quraishi, S. A. TI 25-Hydroxyvitamin D Levels At Initiation Of Critical Care Are Associated With Duration Of Mechanical Ventilation In Critically Ill Surgical Patients SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [McCarthy, C. M.; Blum, L.; Cobb, J. P.; Camargo, C. A.; Quraishi, S. A.] 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 2014 VL 189 MA A1191 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838200181 ER PT J AU Mehta, S Delcroix, M Galie, N Ghofrani, HA Jansa, P Le Brun, FO Perchenet, L Pulido, T Rubin, LJ Sastry, B Simonneau, G Sitbon, O Souza, R Torbicki, A Channick, RN AF Mehta, S. Delcroix, M. Galie, N. Ghofrani, H. A. Jansa, P. Le Brun, F. O. Perchenet, L. Pulido, T. Rubin, L. J. Sastry, B. Simonneau, G. Sitbon, O. Souza, R. Torbicki, A. Channick, R. N. TI Macitentan Reduced All-Cause Hospitalizations In Patients With Pulmonary Arterial Hypertension: Data 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. [Delcroix, M.] Univ Hosp Gasthuisberg, Leuven, Belgium. [Galie, N.] Univ Bologna, Bologna, Italy. [Ghofrani, H. A.] Univ Hosp Giessen & Marburg, Giessen, Germany. [Ghofrani, H. A.] German Ctr Lung Res, Giessen, Germany. [Ghofrani, H. A.] Imperial Coll London, Giessen, Germany. [Jansa, P.] Charles Univ Prague, Prague, Czech Republic. [Le Brun, F. O.; Perchenet, L.] Actel Pharmaceut Ltd, Allschwil, Switzerland. [Pulido, T.] Natl Inst Cardiol, Mexico City, DF, Mexico. [Rubin, L. J.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Sastry, B.] CARE Hosp, Hyderabad, Andhra Pradesh, India. [Simonneau, G.; Sitbon, O.] Univ Paris Sud, Hop Bicetre, Le Kremlin Bicetre, France. [Souza, R.] Univ Sao Paulo, Sao Paulo, Brazil. [Torbicki, A.] ECZ Otwock, Ctr Postgrad Med Educ, Otwock, Poland. [Channick, R. N.] 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 2014 VL 189 MA A2458 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838201617 ER PT J AU Melzer, AC Uman, J Au, DH AF Melzer, A. C. Uman, J. Au, D. H. TI Predictors Of Decreased Medication Adherence For Hypertensive Patients SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Uman, J.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Au, D. H.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. EM acmelzer@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 2014 VL 189 MA A1410 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838200399 ER PT J AU Montesi, SB Mathai, SK Brenner, LN Gorshkova, I Berdyshev, E Tager, AM Shea, BS AF Montesi, S. B. Mathai, S. K. Brenner, L. N. Gorshkova, I. Berdyshev, E. Tager, A. M. Shea, B. S. TI Docosatetraenyl Lysophosphatidic Acid (lpa) Is Elevated In Exhaled Breath Condensate In Idiopathic Pulmonary Fibrosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Montesi, S. B.; Brenner, L. N.; Tager, A. M.; Shea, B. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mathai, S. K.] Univ Colorado, Aurora, CO USA. [Gorshkova, I.; Berdyshev, E.] Univ Illinois, Chicago, IL USA. EM sbmontesi@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 2014 VL 189 MA A1523 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838200511 ER PT J AU Mortensen, EM Murphy, J Bollinger, M Anzueto, A Fine, M AF Mortensen, E. M. Murphy, J. Bollinger, M. Anzueto, A. Fine, M. TI Electronic Medical Record Based Intervention To Reduce Length Of Stay For Veterans Hospitalized With Pneumonia SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Mortensen, E. M.] Univ Texas Southwestern Med Ctr Dallas, Dallas, TX 75390 USA. [Murphy, J.; Bollinger, M.; Anzueto, A.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Anzueto, A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Fine, M.] VA Pittsburgh Healthcare Syst 151 C, Pittsburgh, PA 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 2014 VL 189 MA A6237 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838206036 ER PT J AU Moschovis, PP Addo-Yobo, E Banajeh, S Chisaka, N Jeena, P MacLeod, WB Mino, G Patel, A Saha, S Santosham, M Christiani, DC Thea, D Qazi, S Hibberd, PL AF Moschovis, P. P. Addo-Yobo, E. Banajeh, S. Chisaka, N. Jeena, P. MacLeod, W. B. Mino, G. Patel, A. Saha, S. Santosham, M. Christiani, D. C. Thea, D. Qazi, S. Hibberd, P. L. TI Stunting Predicts Poor Outcome In Children With Severe Pneumonia SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Moschovis, P. P.; Christiani, D. C.; Hibberd, P. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Addo-Yobo, E.] Kwame Nkrumah Univ Sci & Technol, Kumasi, Ghana. [Banajeh, S.] Sanaa Univ, Sanaa, Yemen. [Chisaka, N.] World Bank, Washington, DC 20433 USA. [Jeena, P.] Univ KwaZulu Natal, Durban, South Africa. [MacLeod, W. B.; Thea, D.] Boston Univ, Boston, MA 02215 USA. [Mino, G.] Childrens Hosp Dr Francisco de Ycaza Bustamante, Guayaquil, Ecuador. [Patel, A.] Indira Gandhi Govt Med Coll, Nagpur, Maharashtra, India. [Saha, S.] Dhaka Shishu Hosp, Dhaka, Bangladesh. [Santosham, M.] Johns Hopkins Univ, Baltimore, MD USA. [Christiani, D. C.] Harvard Sch Publ Hlth, Boston, MA USA. [Qazi, S.] WHO, Geneva, Switzerland. EM petrosm@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 2014 VL 189 MA A1237 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838200227 ER PT J AU Moseson, EM Slatore, CG Golden, SE AF Moseson, E. M. Slatore, C. G. Golden, S. E. TI Adherence To Fleischner Society Guidelines Among Veterans With Pulmonary Nodules In A Clinical Registry SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Moseson, E. M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Moseson, E. M.; Slatore, C. G.; Golden, S. E.] Portland VA Med Ctr, Portland, OR USA. EM emoseson@stanfordalumni.org 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 2014 VL 189 MA A2251 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838201410 ER PT J AU Nguyen, HQ Lee, J Chen, Z Borson, S Adams, SG Herting, J Kohen, R Matute-Bello, G Fan, V AF Nguyen, H. Q. Lee, J. Chen, Z. Borson, S. Adams, S. G. Herting, J. Kohen, R. Matute-Bello, G. Fan, V. TI Associations Between Cognitive Functioning And Functional Status In 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. [Lee, J.; Chen, Z.; Borson, S.; Herting, J.; Kohen, R.; Matute-Bello, G.] Univ Washington, Seattle, WA 98195 USA. [Adams, S. G.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Fan, V.] Univ Washington, VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98195 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 2014 VL 189 MA A2447 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838201606 ER PT J AU Nicholas, JB Huang, JX Hooi, L Pan, L Huang, Y Yap, S Ramesha, H Kossen, K Emayan, K Misialek, S Rajagopalan, R Dolim, K Kim, S Zhen, C Henshilwood, J Radhakrishnan, R Sastry, SV Hu, M Tager, AM Castelino, FV Schaefer, CJ Seiwert, SD Buckman, BO AF Nicholas, J. B. Huang, J. -X. Hooi, L. Pan, L. Huang, Y. Yap, S. Ramesha, H. Kossen, K. Emayan, K. Misialek, S. Rajagopalan, R. Dolim, K. Kim, S. Zhen, C. Henshilwood, J. Radhakrishnan, R. Sastry, S. V. Hu, M. Tager, A. M. Castelino, F. V. Schaefer, C. J. Seiwert, S. D. Buckman, B. O. TI Discovery And Anti-Fibrotic Activity Of Novel Antagonists Of Lysophosphatidic Acid Receptor 1 (lpar1) SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Nicholas, J. B.; Huang, J. -X.; Hooi, L.; Pan, L.; Huang, Y.; Yap, S.; Ramesha, H.; Kossen, K.; Emayan, K.; Misialek, S.; Rajagopalan, R.; Dolim, K.; Kim, S.; Zhen, C.; Henshilwood, J.; Radhakrishnan, R.; Sastry, S. V.; Hu, M.; Schaefer, C. J.; Seiwert, S. D.; Buckman, B. O.] InterMune Inc, Brisbane, CA USA. [Tager, A. M.; Castelino, F. V.] Massachusetts Gen Hosp, Charlestown, MA USA. EM bbuckman@intermune.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 2014 VL 189 MA A2018 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838201178 ER PT J AU Nygaard, UC Hew, KM Nadeau, K Xiao, L Lv, N Camargo, CA Buist, AS Wilson, SR Strub, P Lavori, P Ma, J AF Nygaard, U. C. Hew, K. M. Nadeau, K. Xiao, L. Lv, N. Camargo, C. A. Buist, A. S. Wilson, S. R. Strub, P. Lavori, P. Ma, J. TI Inflammatory Th1, Th17 And Innate Immunity Serum Biomarkers Are Associated With Level Of Control Among Adults With Uncontrolled Asthma SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Nygaard, U. C.; Hew, K. M.; Lavori, P.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Nygaard, U. C.] Norwegian Inst Publ Hlth, Stanford, CA USA. [Nadeau, K.] Stanford Med Sch, Stanford, CA USA. [Nadeau, K.] Lucile Packard Childrens Hosp, Stanford, CA USA. [Xiao, L.; Lv, N.; Wilson, S. R.; Ma, J.] Palo Alto Med Fdn Res Inst, Palo Alto, CA USA. [Camargo, C. A.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Buist, A. S.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Strub, P.] Kaiser Permanente, San Francisco, CA USA. [Ma, J.] Stanford Prevent Res Ctr, Palo Alto, CA USA. EM unygaard@stanford.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 2014 VL 189 MA A4250 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838203604 ER PT J AU Oudiz, RJ Langer, A Rubin, L Channick, RN Tapson, VF Tan, MK Patni, R Spindler, CN Mclaughlin, V AF Oudiz, R. J. Langer, A. Rubin, L. Channick, R. N. Tapson, V. F. Tan, M. K. Patni, R. Spindler, C. N. Mclaughlin, V. TI The Pulmonary Arterial Hypertension Quality Enhancement Research Initiative (pah-Queri-X Registry): Differences Between Incident And Prevalent Pah SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Oudiz, R. J.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Langer, A.; Tan, M. K.; Spindler, C. N.] Canadian Heart Res Ctr, Toronto, ON, Canada. [Rubin, L.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Channick, R. N.] Massachsetts Gen Hosp, Boston, MA USA. [Tapson, V. F.] Duke Univ, Med Ctr, Durham, NC USA. [Patni, R.] Actel Pharmaceut US Inc, San Francisco, CA USA. [Mclaughlin, V.] Univ Michigan, Ann Arbor, MI 48109 USA. EM goudiz@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 2014 VL 189 MA A4740 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838204232 ER PT J AU Polverino, E Torres, A Sibila, O Ferrer, M Menendez, R Mensa, J Gabarrus, A Sellares, J Restrepo, MI Anzueto, A Niederman, M Agusti, C AF Polverino, E. Torres, A. Sibila, O. Ferrer, M. Menendez, R. Mensa, J. Gabarrus, A. Sellares, J. Restrepo, M. I. Anzueto, A. Niederman, M. Agusti, C. TI Corticosteroids In Severe Community-Acquired Pneumonia: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Polverino, E.; Torres, A.; Ferrer, M.; Gabarrus, A.; Sellares, J.; Agusti, C.] CIBERES, Hosp Clin IDIBAPS, Barcelona, Spain. [Sibila, O.] Hosp Santa Creu & Sant Pau, Barcelona, Spain. [Menendez, R.] CIBERES, Hosp Univ Politecn La Fe, Valencia, Spain. [Mensa, J.] Hosp Clin Barcelona, Barcelona, Spain. [Restrepo, M. I.] Univ Texas Hlth Sci Ctr San Antonio, STVHCS, San Antonio, TX 78229 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. Winthrop Univ Hosp, Mineola, NY 11501 USA. EM epolveri@clinic.ub.es 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 2014 VL 189 MA A5226 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838204710 ER PT J AU Raby, BA Toledo, D Yonker, LM Henske, E Kinane, TB AF Raby, B. A. Toledo, D. Yonker, L. M. Henske, E. Kinane, T. B. TI A Multidisciplinary Approach To The Evaluation And Care Of Patients With Inherited Lung Disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Raby, B. A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Raby, B. A.] Harvard Med Sch, Boston, MA USA. [Toledo, D.; Henske, E.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA. [Yonker, L. M.; Kinane, T. B.] Massachusetts Gen Hosp, Boston, MA 02114 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 2014 VL 189 MA A2774 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838202052 ER PT J AU Rahaghi, FN Estepar, RS Gladysheva, E Ross, J Winkler, T Harris, RS Washko, GR AF Rahaghi, F. N. Estepar, R. San Jose Gladysheva, E. Ross, J. Winkler, T. Harris, R. S. Washko, G. R. TI CT Based Imaging As A Potential Tool For Assessing Pulmonary Vascular Response To Pharmaceuticals SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Rahaghi, F. N.; Estepar, R. San Jose; Ross, J.; Washko, G. R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Gladysheva, E.; Winkler, T.; Harris, R. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gladysheva, E.; Winkler, T.; Harris, R. S.] Harvard Med Sch, Boston, MA USA. EM frahaghi@partners.org NR 1 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 2014 VL 189 MA A6710 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838206508 ER PT J AU Rinne, ST Collins, BF Perkins, M Au, DH Liu, CF AF Rinne, S. T. Collins, B. F. Perkins, M. Au, D. H. Liu, C-F TI Weekend Discharges After COPD Hospitalizations Are Not Associated With A Higher Risk Of Readmission SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Rinne, S. T.; Au, D. H.] Univ Washington, Seattle, WA 98195 USA. [Rinne, S. T.; Collins, B. F.; Perkins, M.; Liu, C-F] VA Puget Sound Hlth Care Syst, 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 2014 VL 189 MA A3717 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838203089 ER PT J AU Semler, MW Wheeler, AP Bernard, GR Thompson, BT Rice, TW AF Semler, M. W. Wheeler, A. P. Bernard, G. R. Thompson, B. T. Rice, T. W. TI Conservative Fluid Management Decreases Mortality In Acute Respiratory Distress Syndrome Patients With Low Central Venous Pressure SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Semler, M. W.; Wheeler, A. P.; Bernard, G. R.; Rice, T. W.] Vanderbilt Univ, Nashville, TN 37235 USA. [Thompson, B. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM matthew.semler@gmail.com 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 2014 VL 189 MA A5094 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838204578 ER PT J AU Shahrir, S Rimlamd, D Brown, S Akgun, KM Wongtrakool, C Rodgriguez-Barradas, M Hoo, GS Sharafkhaneh, A Crothers, KA AF Shahrir, S. Rimlamd, D. Brown, S. Akgun, K. M. Wongtrakool, C. Rodgriguez-Barradas, M. Hoo, G. Soo Sharafkhaneh, A. Crothers, K. A. TI Abnormal Pulmonary Findings On CT Scan And Subsequent Smoking Behavior SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Shahrir, S.; Crothers, K. A.] Univ Washington, Seattle, WA 98195 USA. [Rimlamd, D.; Wongtrakool, C.] Atlanta VA Med Ctr, Atlanta, GA USA. [Brown, S.] James J Peters VA Med Ctr, New York, NY USA. [Akgun, K. M.] Yale Univ, VA Connecticut West Haven, West Haven, CT USA. [Wongtrakool, C.] Emory Univ, Atlanta, GA 30322 USA. [Rodgriguez-Barradas, M.; Sharafkhaneh, A.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Hoo, G. Soo] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Sharafkhaneh, A.] Baylor Coll Med, Houston, TX 77030 USA. EM sshahrir@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 2014 VL 189 MA A1078 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838200070 ER PT J AU Sheth, CT Hoo, GS AF Sheth, C. T. Hoo, G. Soo TI Catheter Related Bloodstream Infections: Differences Between Central Line And Picc Line Infections SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Sheth, C. T.; Hoo, G. Soo] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. NR 1 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 2014 VL 189 MA A3119 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838202396 ER PT J AU Slatore, CG Au, DH Golden, SE Ganzini, L AF Slatore, C. G. Au, D. H. Golden, S. E. Ganzini, L. TI Pulmonary Nodule Detection: Association Of Patient-Clinician Communication With Distress SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Slatore, C. G.; Au, D. H.; Golden, S. E.; Ganzini, L.] Portland VA Med Ctr, Portland, OR USA. EM christopher.slatore@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 2014 VL 189 MA A1088 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838200080 ER PT J AU Sulemanji, DS Oto, J Herrmann, J Kaczka, DW Melo, MFV AF Sulemanji, D. S. Oto, J. Herrmann, J. Kaczka, D. W. Melo, M. F. Vidal TI High Peep During Major Abdominal Surgery Improves Intraoperative Elastance And Reduces Lung Derecruitment SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Sulemanji, D. S.; Oto, J.; Melo, M. F. Vidal] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Herrmann, J.] Boston Univ, Boston, MA 02215 USA. [Kaczka, D. W.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 5 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 2014 VL 189 MA A1179 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838200169 ER PT J AU Sullivan, DR Pappas, M Humphrey, LL Slatore, CG AF Sullivan, D. R. Pappas, M. Humphrey, L. L. Slatore, C. G. TI Populations And Individuals: A Systematic Review Of The Psychosocial Impact Of Lung Cancer Screening With Computed Tomography On Patients 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. [Pappas, M.; Humphrey, L. L.] Pacific Northwest Evidence Based Practice Ctr, Portland, OR USA. [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 2014 VL 189 MA A6309 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838206108 ER PT J AU Suter, MJ Adams, DC Villiger, M Miller, AJ Hariri, LP Luster, AD Bouma, BE Medoff, BD AF Suter, M. J. Adams, D. C. Villiger, M. Miller, A. J. Hariri, L. P. Luster, A. D. Bouma, B. E. Medoff, B. D. TI Endobronchial Birefringence Microscopy Of Airway Smooth Muscle In Vivo SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Suter, M. J.; Adams, D. C.; Villiger, M.; Miller, A. J.; Hariri, L. P.; Luster, A. D.; Bouma, B. E.; Medoff, B. D.] Harvard Med Sch, Boston, MA USA. [Suter, M. J.; Adams, D. C.; Villiger, M.; Miller, A. J.; Hariri, L. P.; Luster, A. D.; Bouma, B. E.; Medoff, B. D.] Massachusetts Gen Hosp, Boston, MA 02114 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 2014 VL 189 MA A1044 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838200036 ER PT J AU Szabari, MV Falcao, LR Musch, G AF Szabari, M. V. Falcao, L. R. Musch, G. TI Long-Term Clinically Relevant Ventilator-Induced Lung Injury In Mice SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Szabari, M. V.; Falcao, L. R.; Musch, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Szabari, M. V.; Falcao, L. R.; Musch, G.] Harvard Med Sch, Boston, MA USA. EM mszabari@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 2014 VL 189 MA A1182 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838200172 ER PT J AU Tejera, P O'Mahony, DS Owen, CA Wei, Y Wang, Z Gupta, K Su, L Wurfel, MM Christiani, DC AF Tejera, P. O'Mahony, D. S. Owen, C. A. Wei, Y. Wang, Z. Gupta, K. Su, L. Wurfel, M. M. Christiani, D. C. TI Functional Characterization Of Polymorphisms In The Pi3 (pre-Elafin) Gene And Validation Of Their Contribution To Risk Of Ards SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Tejera, P.; Wei, Y.; Wang, Z.; Su, L.; Christiani, D. C.] HSPH, Boston, MA USA. [O'Mahony, D. S.] Univ Washington, Seattle, WA 98195 USA. [Owen, C. A.; Gupta, K.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA. [Wurfel, M. M.] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. [Christiani, D. C.] Massachusetts Gen Hosp, Boston, MA 02114 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 2014 VL 189 MA A4996 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838204488 ER PT J AU Trivedi, M Sharma, S Rifas-Shiman, S Camargo, CA Weiss, ST Gillman, M Gold, D Demeo, DL Litonjua, AA AF Trivedi, M. Sharma, S. Rifas-Shiman, S. Camargo, C. A. Weiss, S. T. Gillman, M. Gold, D. Demeo, D. L. Litonjua, A. A. TI Maternal Intake Of Dietary Methyl Donors In Pregnancy And Childhood Asthma At 7 Years SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Trivedi, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sharma, S.] Channing Labs, Boston, MA USA. [Rifas-Shiman, S.; Gillman, M.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Camargo, C. A.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Weiss, S. T.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Gold, D.] Harvard Sch Publ Hlth, Boston, MA USA. [Demeo, D. L.; Litonjua, A. A.] Brigham & Womens Hosp, Boston, MA 02115 USA. EM remtr@channing.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 2014 VL 189 MA A5118 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838204602 ER PT J AU Truwit, JD Bernard, GR Steingrub, J Matthay, MA Liu, K Albertson, TE Brower, RG Shanholtz, C Rock, P Douglas, IS DeBoisblanc, BP Hough, CL Hite, RD Thompson, BT AF Truwit, J. D. Bernard, G. R. Steingrub, J. Matthay, M. A. Liu, K. Albertson, T. E. Brower, R. G. Shanholtz, C. Rock, P. Douglas, I. S. DeBoisblanc, B. P. Hough, C. L. Hite, R. D. Thompson, B. T. CA ARDSNet TI Sails: Statins For Acutely Injured Lungs (ards) From Sepsis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Truwit, J. D.] Univ Virginia, Charlottesville, VA USA. [Bernard, G. R.] Vanderbilt Univ, Ctr Lung Res, Nashville, TN 37232 USA. [Steingrub, J.] Tufts Sch Med, Springfield, MA USA. [Matthay, M. A.; Liu, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Albertson, T. E.] Univ Calif Davis, Sacramento, CA 95817 USA. [Brower, R. G.] Johns Hopkins Univ, Baltimore, MD USA. [Shanholtz, C.; Rock, P.] Univ Maryland, Baltimore, MD 21201 USA. [Douglas, I. S.] Univ Colorado Denver, Denver, CO USA. [Douglas, I. S.] Denver Hlth Med Ctr, Denver, CO USA. [DeBoisblanc, B. P.] LSU, Heatlh Sci Ctr, New Orleans, LA USA. [Hough, C. L.] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. [Hite, R. D.] Wake Forest Sch Med, Winston Salem, NC USA. [Thompson, B. T.] 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 2014 VL 189 MA A5088 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838204572 ER PT J AU Voscopoulos, C MacNabb, CM Freeman, JE George, E AF Voscopoulos, C. MacNabb, C. M. Freeman, J. E. George, E. TI Identification Of Patients At Risk For Post-Operative Apnea And Opioid-Induced Respiratory Depression Using Non-Invasive Respiratory Volume Monitoring In The Post-Anesthesia Care Unit Versus Using Pre-Operative Diagnosis Of Obstructive Sleep Apnea SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Voscopoulos, C.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA. [MacNabb, C. M.; Freeman, J. E.] Resp Mot Inc, Waltham, MA USA. [George, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jenny.freeman@respiratorymotion.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 2014 VL 189 MA A5122 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838204606 ER PT J AU Wiener, RS Slatore, CG Bolton, R Koppelman, E Au, DH Clark, JA AF Wiener, R. S. Slatore, C. G. Bolton, R. Koppelman, E. Au, D. H. Clark, J. A. TI Attitudes Of Va Pulmonologists Towards Implementation Of Low Dose CT Screening For Lung Cancer: Results Of A National Survey SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Wiener, R. S.; Bolton, R.; Koppelman, E.; Clark, J. A.] Edith Nourse Rogers Mem VA Hosp, Bedford, MA USA. [Wiener, R. S.; Slatore, C. G.] Portland VA Med Ctr, Portland, OR USA. [Au, D. H.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. EM rwiener@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 2014 VL 189 MA A2254 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838201413 ER PT J AU Winkler, T Golnabi, AH Greenblatt, EE Harris, RS Venegas, JG AF Winkler, T. Golnabi, A. H. Greenblatt, E. E. Harris, R. S. Venegas, J. G. TI Can Variability In Tidal Volume Explain Fluctuations In Respiratory Resistance? SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Winkler, T.; Golnabi, A. H.; Greenblatt, E. E.; Harris, R. S.; Venegas, J. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Winkler, T.; Golnabi, A. H.; Harris, R. S.; Venegas, J. G.] Harvard Med Sch, Boston, MA USA. [Winkler, T.; Greenblatt, E. E.] MIT, 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 2014 VL 189 MA A2672 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838201830 ER PT J AU Wright, LS Permaul, P Petty, C Fu, C Gold, DR Phipatanakul, W AF Wright, L. S. Permaul, P. Petty, C. Fu, C. Gold, D. R. Phipatanakul, W. TI Snoring, Sleep And Tv Time In A School-Aged Cohort Of Inner-City Asthmatics SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Wright, L. S.] Harvard Med Sch, Brigham & Womens Hosital, Boston, MA USA. [Permaul, P.] MassGen Hosp Children, Boston, MA USA. [Petty, C.; Phipatanakul, W.] Boston Childrens Hosp, Boston, MA USA. [Fu, C.; Gold, D. R.] Brigham & Womens Hosp, Boston, MA 02115 USA. EM lwright8@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 2014 VL 189 MA A1333 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838200323 ER PT J AU Wu, AC Butler, M Li, L Fung, V Kharbanda, E Vollmer, WM Miroshnik, I Lieu, T Soumerai, S AF Wu, A. C. Butler, M. Li, L. Fung, V. Kharbanda, E. Vollmer, W. M. Miroshnik, I. Lieu, T. Soumerai, S. TI Adherence To Controller Medications For Asthma Is Poor SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Wu, A. C.] Harvard Med Sch, Lexington, MA USA. [Wu, A. C.] Harvard Pilgrim Hlth Care, Lexington, MA USA. [Wu, A. C.; Butler, M.] Kaiser Permanente Georgia, Atlanta, GA USA. [Li, L.; Miroshnik, I.; Soumerai, S.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Fung, V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kharbanda, E.] HealthPartners Inst Educ & Res, Minneapolis, MN USA. [Vollmer, W. M.] Ctr Hlth Res, Portland, MA USA. [Lieu, T.] Kaiser Permanente Northern Calif, Oakland, 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 2014 VL 189 MA A4041 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838203395 ER PT J AU Yu, S Christiani, DC Thompson, T Gong, MN AF Yu, S. Christiani, D. C. Thompson, T. Gong, M. N. TI Insulin And Development Of Acute Respiratory Distress Syndrome: A Propensity Score Analysis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Yu, S.; Gong, M. N.] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. [Christiani, D. C.] Harvard Sch Publ Hlth, Boston, MA USA. [Thompson, T.; Gong, M. N.] 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 2014 VL 189 MA A1159 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V45TF UT WOS:000209838200149 ER PT J AU Amri, R Bordeianou, LG Sylla, P Berger, DL AF Amri, Ramzi Bordeianou, Liliana G. Sylla, Patricia Berger, David L. TI Obesity, outcomes and quality of care: body mass index increases the risk of wound-related complications in colon cancer surgery SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Colon cancer; Obesity; Body mass index; Postoperative complications; Perioperative outcomes ID SHORT-TERM OUTCOMES; IMPROVEMENT PROGRAM; US ADULTS; COLECTOMY; PREVENTION; FEASIBILITY; INFECTION; HOSPITALS; MORTALITY; IMPACT AB BACKGROUND: Obese patients may face higher complication rates during surgical treatment of colon cancer. The aim of this study was to measure this effect at a high-volume tertiary care center. METHODS: All patients with colon cancer treated surgically at a single center from 2004 through 2011 were reviewed. Multivariate regression assessed relationships of complications and stay outcomes with body mass index (BMI) controlling for age, gender, comorbidity score, surgical approach, and history of smoking. RESULTS: In 1,048 included patients, BMI was a predictor of several complications in both laparoscopic and open procedures. For every increase of BMI by one World Health Organization category, the odds ratios were 1.61 (P < .001) for wound infection and 1.54 (P < .001) for slow healing. Additionally, right colectomies had an odds ratio of 3.23 (P = .017) for wound dehiscence. No further associations with BMI were found. CONCLUSIONS: BMI was incrementally associated with wound-related complications, illustrating how the proliferation of obesity relates to a growing risk for surgical complications. As the surgical community strives to improve the quality of care, patient-controllable factors will play an increasingly important role in cost containment and quality improvement. (C) 2014 Elsevier Inc. All rights reserved. C1 [Berger, David L.] Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Berger, DL (reprint author), Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. EM berger.david@mgh.harvard.edu OI Amri, Ramzi/0000-0001-7416-6650 FU National Center for Advancing Translational Sciences, National Institutes of Health [8UL1TR000170-05]; Harvard University; Dutch Cancer Society; Dutch Digestive Society; Amsterdam University Funds; Royal Netherlands Academy of Arts and Sciences; Fulbright Foundation FX This work was conducted with support from Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 8UL1TR000170-05 and financial contributions from Harvard University and its affiliated academic health care centers).; This work was also supported in part by the Dutch Cancer Society, the Dutch Digestive Society, the Amsterdam University Funds, the Royal Netherlands Academy of Arts and Sciences and the Fulbright Foundation. The authors declare no conflicts of interest. NR 25 TC 20 Z9 20 U1 2 U2 6 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 EI 1879-1883 J9 AM J SURG JI Am. J. Surg. PD JAN PY 2014 VL 207 IS 1 BP 17 EP 23 DI 10.1016/j.amjsurg.2013.05.016 PG 7 WC Surgery SC Surgery GA 268VG UT WOS:000328198100003 PM 24139555 ER PT J AU Waldrop, AE Cohen, BE AF Waldrop, Angela E. Cohen, Beth E. TI Trauma Exposure Predicts Alcohol, Nicotine, and Drug Problems Beyond the Contribution of PTSD and Depression in Patients with Cardiovascular Disease: Data from the Heart and Soul Study SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; SUBSTANCE USE DISORDERS; RISK-FACTORS; PSYCHOLOGICAL TRAUMA; YOUNG-ADULTS; HEALTH; ABUSE; COMORBIDITY; PREVALENCE; VETERANS AB Background and ObjectivesThis study examined the role of lifetime trauma exposure in a longitudinal study of adults with cardiovascular disease to determine the unique contribution of trauma exposure to risk for drug and alcohol problems and smoking. MethodsData were drawn from the Heart and Soul Study, a prospective cohort study designed to determine the mechanisms of associations between psychological factors and increased risk of cardiovascular events in high-risk patients (n=1,022). ResultsLifetime exposure to a higher number of trauma types predicted substance use outcomes beyond risk explained by PTSD and depression. In addition, across trauma types, interpersonal traumas were most strongly associated with substance use problems. ConclusionsOur results suggest that, though PTSD and depression play a role in the association between trauma exposure and substance use, many other factors also contribute; therefore focusing on these psychological comorbidities alone is not sufficient. Scientific SignificanceThe integration of mental health care and/or case management support with primary and specialty medical care may improve detection and treatment for patients with substance use and comorbid mental and physical health problems. Screening for trauma exposure is an important part of good clinical care. (Am J Addict 2014;23:53-61) C1 [Waldrop, Angela E.; Cohen, Beth E.] San Francisco VA Med Ctr, San Francisco, CA USA. [Waldrop, Angela E.; Cohen, Beth E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Waldrop, AE (reprint author), 4150 Clement St,116P, San Francisco, CA 94121 USA. EM angela.waldrop@ucsf.edu FU NHLBI NIH HHS [K23 HL 094765‐01, K23 HL094765, L30 HL104707, R01 HL079235]; NIDA NIH HHS [5K23DA018718‐05, K23 DA018718] NR 32 TC 3 Z9 3 U1 3 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD JAN PY 2014 VL 23 IS 1 BP 53 EP 61 DI 10.1111/j.1521-0391.2013.12053.x PG 9 WC Substance Abuse SC Substance Abuse GA 264RC UT WOS:000327897000009 PM 24313242 ER PT J AU Lee, JH Zheng, Y von Bornstadt, D Wei, Y Balcioglu, A Daneshmand, A Yalcin, N Yu, E Herisson, F Atalay, YB Kim, MH Ahn, YJ Balkaya, M Sweetnam, P Schueller, O Poyurovsky, MV Kim, HH Lo, EH Furie, KL Ayata, C AF Lee, Jeong Hyun Zheng, Yi von Bornstadt, Daniel Wei, Ying Balcioglu, Aygul Daneshmand, Ali Yalcin, Nilufer Yu, Esther Herisson, Fanny Atalay, Yahya B. Kim, Maya H. Ahn, Yong-Joo Balkaya, Mustafa Sweetnam, Paul Schueller, Olivier Poyurovsky, Masha V. Kim, Hyung-Hwan Lo, Eng H. Furie, Karen L. Ayata, Cenk TI Selective ROCK2 inhibition in focal cerebral ischemia SO ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY LA English DT Article AB Objective: Rho-associated kinase (ROCK) is a key regulator of numerous processes in multiple cell types relevant in stroke pathophysiology. ROCK inhibitors have improved outcome in experimental models of acute ischemic or hemorrhagic stroke. However, the relevant ROCK isoform (ROCK1 or ROCK2) in acute stroke is not known. Methods: We characterized the pharmacodynamic and pharmacokinetic profile, and tested the efficacy and safety of a novel selective ROCK2 inhibitor KD025 (formerly SLx-2119) in focal cerebral ischemia models in mice. Results: KD025 dose-dependently reduced infarct volume after transient middle cerebral artery occlusion. The therapeutic window was at least 3 h from stroke onset, and the efficacy was sustained for at least 4 weeks. KD025 was at least as efficacious in aged, diabetic or female mice, as in normal adult males. Concurrent treatment with atorvastatin was safe, but not additive or synergistic. KD025 was also safe in a permanent ischemia model, albeit with diminished efficacy. As one mechanism of protection, KD025 improved cortical perfusion in a distal middle cerebral artery occlusion model, implicating enhanced collateral flow. Unlike isoform-nonselective ROCK inhibitors, KD025 did not cause significant hypotension, a dose-limiting side effect in acute ischemic stroke. Interpretation: Altogether, these data show that KD025 is efficacious and safe in acute focal cerebral ischemia in mice, implicating ROCK2 as the relevant isoform in acute ischemic stroke. Data suggest that selective ROCK2 inhibition has a favorable safety profile to facilitate clinical translation. C1 [Lee, Jeong Hyun; Zheng, Yi; von Bornstadt, Daniel; Wei, Ying; Balcioglu, Aygul; Daneshmand, Ali; Yalcin, Nilufer; Yu, Esther; Herisson, Fanny; Atalay, Yahya B.; Kim, Maya H.; Ahn, Yong-Joo; Balkaya, Mustafa; Kim, Hyung-Hwan; Ayata, Cenk] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Neurovasc Res Lab, Charlestown, MA 02129 USA. [Sweetnam, Paul; Schueller, Olivier] Surface Logix Inc, Brighton, MA 02135 USA. [Poyurovsky, Masha V.] Kadmon Res Inst, New York, NY 10016 USA. [Lo, Eng H.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. [Furie, Karen L.] Rhode Isl Hosp, Dept Neurol, Providence, RI 02903 USA. [Ayata, Cenk] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. [Ayata, Cenk] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Neurosci Intens Care Unit, Boston, MA 02114 USA. RP Ayata, C (reprint author), Massachusetts Gen Hosp, Neurovasc Res Lab, 149 13th St,Room 6403, Charlestown, MA 02129 USA. EM cayata@partners.org OI Lee, Jeong Hyun/0000-0003-0504-0119 FU NINDS NIH HHS [P50 NS051343, R01 NS061505] NR 48 TC 18 Z9 18 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2328-9503 J9 ANN CLIN TRANSL NEUR JI Ann. Clin. Transl. Neurol. PD JAN PY 2014 VL 1 IS 1 BP 2 EP 14 DI 10.1002/acn3.19 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V45KC UT WOS:000209814500002 PM 24466563 ER PT J AU Ciolino, JB Stefanescu, CF Ross, AE Salvador-Culla, B Cortez, P Ford, EM Wymbs, KA Sprague, SL Mascoop, DR Rudina, SS Trauger, SA Cade, F Kohane, DS AF Ciolino, Joseph B. Stefanescu, Cristina F. Ross, Amy E. Salvador-Culla, Borja Cortez, Priscila Ford, Eden M. Wymbs, Kate A. Sprague, Sarah L. Mascoop, Daniel R. Rudina, Shireen S. Trauger, Sunia A. Cade, Fabiano Kohane, Daniel S. TI In vivo performance of a drug-eluting contact lens to treat glaucoma for a month SO BIOMATERIALS LA English DT Article DE Drug delivery; Contact lens; Sustained release; Latanoprost; Glaucoma; Ocular release ID OPEN-ANGLE GLAUCOMA; MEDICATION ADHERENCE; LATANOPROST; DELIVERY; PHARMACOKINETICS; SYSTEMS; RABBIT; EYE AB For nearly half a century, contact lenses have been proposed as a means of ocular drug delivery, but achieving controlled drug release has been a significant challenge. We have developed a drug-eluting contact lens designed for prolonged delivery of latanoprost for the treatment of glaucoma, the leading cause of irreversible blindness worldwide. Latanoprost-eluting contact lenses were created by encapsulating latanoprost-poly(lactic-co-glycolic acid) films in methafilcon by ultraviolet light polymerization. In vitro and in vivo studies showed an early burst of drug release followed by sustained release for one month. Contact lenses containing thicker drug-polymer films demonstrated released a greater amount of drug after the initial burst. In vivo, single contact lenses were able to achieve, for at least one month, latanoprost concentrations in the aqueous humor that were comparable to those achieved with topical latanoprost solution, the current first-line treatment for glaucoma. The lenses appeared safe in cell culture and animal studies. This contact lens design can potentially be used as a treatment for glaucoma and as a platform for other ocular drug delivery applications. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Ciolino, Joseph B.; Stefanescu, Cristina F.; Ross, Amy E.; Salvador-Culla, Borja; Cade, Fabiano] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Ciolino, Joseph B.; Stefanescu, Cristina F.; Ross, Amy E.; Salvador-Culla, Borja; Cortez, Priscila; Ford, Eden M.; Wymbs, Kate A.; Sprague, Sarah L.; Mascoop, Daniel R.; Rudina, Shireen S.; Kohane, Daniel S.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Ciolino, Joseph B.; Stefanescu, Cristina F.; Ross, Amy E.; Salvador-Culla, Borja; Cortez, Priscila; Ford, Eden M.; Wymbs, Kate A.; Sprague, Sarah L.; Mascoop, Daniel R.; Rudina, Shireen S.; Kohane, Daniel S.] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Anesthesiol,Div Crit Care Med,Lab Biomat & D, Boston, MA 02115 USA. [Trauger, Sunia A.] Harvard Univ, Ctr Syst Biol, Cambridge, MA 02138 USA. RP Kohane, DS (reprint author), Childrens Hosp, Dept Anesthesiol, 300 Longwood Ave, Boston, MA 02115 USA. EM daniel.kohane@childrens.harvard.edu FU NEI [1K08EY019686-01]; Massachusetts Lions Eye Research Fund; New England Cornea Transplant Fund; NIGMS [GM073626]; Eleanor and Miles Shore Foundation; Research to Prevent Blindness, Inc., NY, NY FX The authors wish to thank Professor Stephen L. Buchwald for use of gas chromatograph equipment and Pedro L. Arrechea for assistance with gas chromatography experiments. This research was funded by NEI 1K08EY019686-01 (JBC), Massachusetts Lions Eye Research Fund (JBC), New England Cornea Transplant Fund (JBC), NIGMS GM073626 (DSK), Eleanor and Miles Shore Foundation (JBC), and by a Career Development Award from Research to Prevent Blindness, Inc., NY, NY (JBC). NR 34 TC 24 Z9 24 U1 12 U2 61 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 EI 1878-5905 J9 BIOMATERIALS JI Biomaterials PD JAN PY 2014 VL 35 IS 1 BP 432 EP 439 DI 10.1016/j.biomaterials.2013.09.032 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 266EL UT WOS:000328006100043 PM 24094935 ER PT J AU Charidimou, A Imaizumi, T Biffi, A Kang, DW Peeters, A Baron, JC Hernandez, M Montaner, J Kim, JS Naka, H Smith, EE Vandermeeren, Y Viswanathan, A Greenberg, MS Werring, DJ Burnell, M Yakushiji, Y Laloux, P Jager, HR AF Charidimou, A. Imaizumi, T. Biffi, A. Kang, D. W. Peeters, A. Baron, J-C. Hernandez, M. Montaner, J. Kim, J. S. Naka, H. Smith, E. E. Vandermeeren, Y. Viswanathan, A. Greenberg, M. S. Werring, D. J. Burnell, M. Yakushiji, Y. Laloux, P. Jager, H. R. TI Cerebral microbleeds, MRI-defined microangiopathy subtype and recurrent spontaneous intracerebral haemorrhage risk: systematic review and meta-analysis SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Charidimou, A.] UCL Inst Neurol, Stroke Res Grp, London, England. [Charidimou, A.; Werring, D. J.] Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England. [Imaizumi, T.] Kushiro City Gen Hosp, Dept Neurosurg, Kushiro, Hokkaido, Japan. [Biffi, A.; Viswanathan, A.; Greenberg, M. S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hemorrhag Stroke Res Program,Stroke Res Ctr, Boston, MA USA. [Kang, D. W.; Kim, J. S.] Univ Ulsan, Coll Med, Asian Med Ctr, Dept Neurol, Seoul, South Korea. [Peeters, A.] Clin Univ UCL St Luc, Dept Neurol, Brussels, Belgium. [Baron, J-C.] Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 2QQ, England. [Hernandez, M.; Montaner, J.] Univ Autonoma Barcelona, Neurovasc Res Lab, E-08193 Barcelona, Spain. [Hernandez, M.; Montaner, J.] Univ Autonoma Barcelona, Neurovasc Unit, Dept Neurol, E-08193 Barcelona, Spain. [Hernandez, M.; Montaner, J.] Univ Autonoma Barcelona, Dept Med, E-08193 Barcelona, Spain. [Naka, H.] Hiroshima Univ, Suiseikai Kajikawa Hosp, Grad Sch Biomed Sci, Dept Neurol, Hiroshima, Japan. [Smith, E. E.] Univ Calgary, Dept Clin Neurosci, Calgary Stroke Program, Calgary, AB, Canada. [Vandermeeren, Y.] Catholic Univ Louvain, CHU Mt Godinne, Dept Neurol, B-1200 Brussels, Belgium. [Werring, D. J.] UCL Inst Neurol, Stroke Res Grp, Dept Brain Repair & Rehabil, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2014 VL 37 SU 1 BP 28 EP 28 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA V43ZE UT WOS:000209718500032 ER PT J AU Shoamanesh, A Ayres, A Schwab, K Rosand, J Gurol, ME Viswanathan, A Greenberg, SM AF Shoamanesh, A. Ayres, A. Schwab, K. Rosand, J. Gurol, M. E. Viswanathan, A. Greenberg, S. M. TI The Yin and Yang of Superficial Siderosis and Microbleeds in Cerebral Amyloid Angiopathy SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Shoamanesh, A.; Ayres, A.; Schwab, K.; Rosand, J.; Gurol, M. E.; Viswanathan, A.; Greenberg, S. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2014 VL 37 SU 1 BP 116 EP 116 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA V43ZE UT WOS:000209718500168 ER PT J AU Rannikmaae, K Davies, G Thomson, P Devan, W Bevan, S Traylor, M Falcone, GJ Anderson, C Rost, N Woo, D Markus, H Seshadri, S Rosand, J Van Agtmael, T Sudlow, CLM AF Rannikmaae, K. Davies, G. Thomson, P. Devan, W. Bevan, S. Traylor, M. Falcone, G. J. Anderson, C. Rost, N. Woo, D. Markus, H. Seshadri, S. Rosand, J. Van Agtmael, T. Sudlow, C. L. M. CA METASTROKE Consortium CHARGE Consortium ISGC TI The contribution of variants in collagen IV genes to common cerebrovascular phenotypes SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Rannikmaae, K.; Sudlow, C. L. M.] Univ Edinburgh, Div Clin Neurosci, Edinburgh, Midlothian, Scotland. [Davies, G.] Univ Edinburgh, Dept Psychol, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland. [Thomson, P.; Sudlow, C. L. M.] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland. [Devan, W.; Falcone, G. J.; Anderson, C.; Rost, N.; Rosand, J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Bevan, S.; Markus, H.] Univ Cambridge, Clin Neurosci, Cambridge, England. [Traylor, M.] St Georges Univ London, Stroke & Dementia Res Ctr, London, England. [Woo, D.] Univ Cincinnati, Dept Neurol & Rehabil Med, Cincinnati, OH USA. [Seshadri, S.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Van Agtmael, T.] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2014 VL 37 SU 1 BP 136 EP 137 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA V43ZE UT WOS:000209718501025 ER PT J AU Falcone, GJ Woo, D Brown, WM Tirschwell, DL Selim, M Brown, DL Silliman, SL Worrall, BB Meschia, JF Montaner, J Lindgren, A Slowik, A Langefeld, CD Rosand, J AF Falcone, G. J. Woo, D. Brown, W. M. Tirschwell, D. L. Selim, M. Brown, D. L. Silliman, S. L. Worrall, B. B. Meschia, J. F. Montaner, J. Lindgren, A. Slowik, A. Langefeld, C. D. Rosand, J. CA Int Stroke Genetics Consortium TI Meta-Analysis of Genome-Wide Association Studies Identifies 1q22 as a Novel Susceptibility Locus for Intracerebral Hemorrhage SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Falcone, G. J.; Rosand, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Woo, D.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Brown, W. M.; Langefeld, C. D.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Tirschwell, D. L.] Univ Washington, Seattle, WA 98195 USA. [Selim, M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Brown, D. L.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Silliman, S. L.] Univ Florida, Coll Med, Jacksonville, FL USA. [Worrall, B. B.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Meschia, J. F.] Mayo Clin, Jacksonville, FL 32224 USA. [Montaner, J.] Univ Autonoma Barcelona, E-08193 Barcelona, Spain. [Lindgren, A.] Lund Univ, Lund, Sweden. [Slowik, A.] Jagiellonian Univ, Coll Med, Krakow, Poland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2014 VL 37 SU 1 BP 144 EP 144 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA V43ZE UT WOS:000209718501036 ER PT J AU Shoamanesh, A Ayres, A Schwab, K Rosand, J Gurol, ME Greenberg, SM Viswanathan, A AF Shoamanesh, A. Ayres, A. Schwab, K. Rosand, J. Gurol, M. E. Greenberg, S. M. Viswanathan, A. TI Depression and Apathy Are Related to Burden of Microvascular Lesions in Cerebral Amyloid Angiopathy SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Shoamanesh, A.; Ayres, A.; Schwab, K.; Rosand, J.; Gurol, M. E.; Greenberg, S. M.; Viswanathan, A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2014 VL 37 SU 1 BP 184 EP 184 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA V43ZE UT WOS:000209718501095 ER PT J AU Berkhemer, OA Majoie, CBLM Yoo, AJ Dippel, DW AF Berkhemer, O. A. Majoie, C. B. L. M. Yoo, A. J. Dippel, D. W. TI Safety and Effectiveness of Stent Retriever usage in Acute lschemic Stroke: A systematic review and meta-analysis SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Berkhemer, O. A.; Majoie, C. B. L. M.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. [Yoo, A. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dippel, D. W.] Univ Med Ctr, Erasmus MC, Rotterdam, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2014 VL 37 SU 1 MA R0401 BP 258 EP 258 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA V43ZE UT WOS:000209718502029 ER PT J AU Lindgren, A Bevan, S Fernandez-Cadenas, I Jern, C Jimenez-Conde, J Lee, JM Lenmens, R Maguire, JM Rost, N Rothwell, PM Strbian, D Sudlow, CLM Woo, D Worrall, BB AF Lindgren, A. Bevan, S. Fernandez-Cadenas, I. Jern, C. Jimenez-Conde, J. Lee, J. -M. Lenmens, R. Maguire, J. M. Rost, N. Rothwell, P. M. Strbian, D. Sudlow, C. L. M. Woo, D. Worrall, B. B. CA ISGC-Int Stroke Genetics Giscome-Genetics Ischaemic Stroke TI GISCOME - Genetics of Ischaemic Stroke Outcome study SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Lindgren, A.] Skane Univ Hosp, Dept Neurol, Lund, Sweden. [Lindgren, A.] Lund Univ, Lund, Sweden. [Bevan, S.] Univ Cambridge, Dept Neurol, Cambridge, England. [Fernandez-Cadenas, I.] Fundacio Docencia & Recerca Mutuaterrassa, Stroke Pharmacogen & Genet, Terrassa, Barcelona, Spain. [Jern, C.] Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Inst Biomed, Gothenburg, Sweden. [Jimenez-Conde, J.] Univ Autonoma Barcelona, IMIM Pare Salut Mar, E-08193 Barcelona, Spain. [Lee, J. -M.] Washington Univ, Sch Med, St Louis, MO USA. [Lenmens, R.] Katholieke Univ Leuven, Leuven, Belgium. [Maguire, J. M.] Univ Newcastle, Fac Hlth & Med, Newcastle, NSW 2300, Australia. [Rost, N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rothwell, P. M.] Univ Oxford, Dept Clin Neurol, Oxford, England. [Strbian, D.] Univ Helsinki, Cent Hosp, Helsinki, Finland. [Sudlow, C. L. M.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Woo, D.] Univ Cincinnati, Dept Neurol & Rehabil Med, Cincinnati, OH USA. [Worrall, B. B.] Univ Virginia Hlth Syst, Charlottesville, VA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2014 VL 37 SU 1 MA R0537 BP 285 EP 285 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA V43ZE UT WOS:000209718502079 ER PT J AU Bouts, MJ McIntosh, E Bezerra, R Diwan, I Mocking, SJ Garg, P Kimberly, WT Arsava, EM Copen, WA Schaefer, PW Ay, H Singhal, AB Rosen, BR Dijkhuizen, RM Wu, O AF Bouts, M. J. McIntosh, E. Bezerra, R. Diwan, I. Mocking, S. J. Garg, P. Kimberly, W. T. Arsava, E. M. Copen, W. A. Schaefer, P. W. Ay, H. Singhal, A. B. Rosen, B. R. Dijkhuizen, R. M. Wu, O. TI Effect of patient population size on the accuracy of tissue outcome prediction using MR imaging-based predictive algorithms SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Bouts, M. J.; McIntosh, E.; Bezerra, R.; Diwan, I.; Mocking, S. J.; Garg, P.; Kimberly, W. T.; Arsava, E. M.; Ay, H.; Rosen, B. R.; Wu, O.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Copen, W. A.; Schaefer, P. W.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Singhal, A. B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Dijkhuizen, R. M.] Univ Med Ctr Utrecht, Image Sci Inst, Biomed MR Imaging & Spect Grp, Utrecht, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2014 VL 37 SU 1 MA B1910 BP 496 EP 496 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA V43ZE UT WOS:000209718504010 ER PT J AU Brouwers, HB Battey, TWK Ciura, VA Falcone, GJ Ayres, AM Vashkevich, A Schwab, K Anderson, CD Greenberg, SM Pomerantz, SR Ortiz, CJ Goldstein, JN Gonzalez, RG Rosand, J Romero, JM AF Brouwers, H. B. Battey, T. W. K. Ciura, V. A. Falcone, G. J. Ayres, A. M. Vashkevich, A. Schwab, K. Anderson, C. D. Greenberg, S. M. Pomerantz, S. R. Ortiz, C. J. Goldstein, J. N. Gonzalez, R. G. Rosand, J. Romero, J. M. TI Rate of Contrast Extravasation on CT Angiography Predicts Hematoma Expansion and Mortality in Primary Intracerebral Hemorrhage SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Brouwers, H. B.; Battey, T. W. K.; Ciura, V. A.; Falcone, G. J.; Ayres, A. M.; Vashkevich, A.; Schwab, K.; Anderson, C. D.; Greenberg, S. M.; Pomerantz, S. R.; Ortiz, C. J.; Goldstein, J. N.; Gonzalez, R. G.; Rosand, J.; Romero, J. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Brouwers, H. B.] Univ Utrecht, Univ Med Ctr Utrecht, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2014 VL 37 SU 1 MA B2107 BP 533 EP 533 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA V43ZE UT WOS:000209718504076 ER PT J AU Catanese, L Shoamanesh, A Lau, H Romero, JR Babikian, V Kase, KS Pikula, A AF Catanese, L. Shoamanesh, A. Lau, H. Romero, J. R. Babikian, V. Kase, K. S. Pikula, A. TI Predictors of Hypertensive Changes on MRI in a Young Stroke Population SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Catanese, L.] Boston Univ, Med Ctr, Boston, MA USA. [Shoamanesh, A.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Lau, H.; Romero, J. R.; Babikian, V.; Kase, K. S.; Pikula, A.] Boston Univ, Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2014 VL 37 SU 1 MA B2536 BP 625 EP 625 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA V43ZE UT WOS:000209718505026 ER PT J AU Pandian, JD Sylaja, PN Kaul, S Khurana, D Padma, MV Thankachan, T Arora, D Titus, P Singhal, A AF Pandian, J. D. Sylaja, P. N. Kaul, S. Khurana, D. Padma, M. V. Thankachan, T. Arora, D. Titus, P. Singhal, A. TI Intravenous and Intra-arterial Thrombolysis In India: The Indo-US Stroke Project SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Pandian, J. D.] Christian Med Coll & Hosp, Ludhiana, Punjab, India. [Sylaja, P. N.] Sree Chitra Tirunal Inst Med Sci & Technol, Thiruvananthapuram, Kerala, India. [Kaul, S.] Nizam Inst Med Sci, Hyderabad, Andhra Pradesh, India. [Khurana, D.] Postgrad Inst Med Educ & Res, Chandigarh 160012, India. [Padma, M. V.] All India Inst Med Sci, New Delhi, India. [Thankachan, T.; Singhal, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Arora, D.; Titus, P.] Christian Med Coll Ludhiana, Ludhiana, Punjab, India. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2014 VL 37 SU 1 MA B2915 BP 687 EP 687 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA V43ZE UT WOS:000209718505135 ER PT J AU Mehan, MR Williams, SA Siegfried, JM Bigbee, WL Weissfeld, JL Wilson, DO Pass, HI Rom, WN Muley, T Meister, M Franklin, W Miller, YE Brody, EN Ostroff, RM AF Mehan, Michael R. Williams, Stephen A. Siegfried, Jill M. Bigbee, William L. Weissfeld, Joel L. Wilson, David O. Pass, Harvey I. Rom, William N. Muley, Thomas Meister, Michael Franklin, Wilbur Miller, York E. Brody, Edward N. Ostroff, Rachel M. TI Validation of a blood protein signature for non-small cell lung cancer SO CLINICAL PROTEOMICS LA English DT Article DE Lung cancer; Biomarker; SOMAmer; Proteomic; Squamous cell carcinoma; Diagnosis; Preanalytic variability; Sample bias AB Background: CT screening for lung cancer is effective in reducing mortality, but there are areas of concern, including a positive predictive value of 4% and development of interval cancers. A blood test that could manage these limitations would be useful, but development of such tests has been impaired by variations in blood collection that may lead to poor reproducibility across populations. Results: Blood-based proteomic profiles were generated with SOMAscan technology, which measured 1033 proteins. First, preanalytic variability was evaluated with Sample Mapping Vectors (SMV), which are panels of proteins that detect confounders in protein levels related to sample collection. A subset of well collected serum samples not influenced by preanalytic variability was selected for discovery of lung cancer biomarkers. The impact of sample collection variation on these candidate markers was tested in the subset of samples with higher SMV scores so that the most robust markers could be used to create disease classifiers. The discovery sample set (n = 363) was from a multi-center study of 94 non-small cell lung cancer (NSCLC) cases and 269 long-term smokers and benign pulmonary nodule controls. The analysis resulted in a 7-marker panel with an AUC of 0.85 for all cases (68% adenocarcinoma, 32% squamous) and an AUC of 0.93 for squamous cell carcinoma in particular. This panel was validated by making blinded predictions in two independent cohorts (n = 138 in the first validation and n = 135 in the second). The model was recalibrated for a panel format prior to unblinding the second cohort. The AUCs overall were 0.81 and 0.77, and for squamous cell tumors alone were 0.89 and 0.87. The estimated negative predictive value for a 15% disease prevalence was 93% overall and 99% for squamous lung tumors. The proteins in the classifier function in destruction of the extracellular matrix, metabolic homeostasis and inflammation. Conclusions: Selecting biomarkers resistant to sample processing variation led to robust lung cancer biomarkers that performed consistently in independent validations. They form a sensitive signature for detection of lung cancer, especially squamous cell histology. This non-invasive test could be used to improve the positive predictive value of CT screening, with the potential to avoid invasive evaluation of nonmalignant pulmonary nodules. C1 [Mehan, Michael R.; Williams, Stephen A.; Brody, Edward N.; Ostroff, Rachel M.] SomaLogic Inc, Boulder, CO USA. [Siegfried, Jill M.] Univ Pittsburgh, Sch Med, Inst Canc, Pittsburgh, PA USA. [Weissfeld, Joel L.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Pass, Harvey I.] NYU, Sch Med, Langone Med Ctr, New York, NY USA. [Pass, Harvey I.] NYU, Sch Med, Ctr Canc, New York, NY USA. [Rom, William N.] NYU, Sch Med, New York, NY USA. [Muley, Thomas; Meister, Michael] Univ Heidelberg Hosp, Thoraxklin, Heidelberg, Germany. [Muley, Thomas; Meister, Michael] TLRC H, Heidelberg, Germany. [Franklin, Wilbur; Miller, York E.] Univ Colorado, Sch Med, Ctr Canc, Aurora, CO USA. [Miller, York E.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Ostroff, RM (reprint author), SomaLogic Inc, Boulder, CO USA. EM rostroff@somalogic.com FU SPORE in Lung Cancer [P50 090440, U01CA86137, U01CA84968]; NCI Cancer Center Support Grant [5P30CA016056, 5P30CA047904, P30 CA46934]; NCI SPORE in Lung Cancer [P50 CA58187]; LUNGevity Foundation; SomaLogic FX SPORE in Lung Cancer P50 090440 (JMS, JWL, DOW, WLB), U01CA86137 (WR, HP), U01CA84968 (WLB), NCI Cancer Center Support Grant 5P30CA016056 (RPCI), and 5P30CA047904 (PITT), NCI SPORE in Lung Cancer P50 CA58187 (WF and YEM), NCI Cancer Center Support Grant, P30 CA46934 (WF and YEM) and an Early Detection Award from the LUNGevity Foundation (YEM).; SomaLogic funded the proteomic analysis. NR 54 TC 20 Z9 20 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1542-6416 EI 1559-0275 J9 CLIN PROTEOM JI Clin. Proteom. PY 2014 VL 11 AR 32 DI 10.1186/1559-0275-11-32 PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA V42YR UT WOS:000209649600026 PM 25114662 ER PT J AU Gbabe, OF Okwundu, CI Dedicoat, M Freeman, EE AF Gbabe, Oluwatoyin F. Okwundu, Charles I. Dedicoat, Martin Freeman, Esther E. TI Treatment of severe or progressive Kaposi's sarcoma in HIV-infected adults SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review DE Antineoplastic Agents [therapeutic use]; Doxorubicin [therapeutic use]; HIV Infections [complications]; Liposomes; Randomized Controlled Trials as Topic; Sarcoma, Kaposi [therapy; virology]; Skin Neoplasms [therapy]; Tretinoin [therapeutic use]; Humans ID ACTIVE ANTIRETROVIRAL THERAPY; PEGYLATED-LIPOSOMAL DOXORUBICIN; PROSPECTIVE RANDOMIZED-TRIAL; AIDS MALIGNANCY CONSORTIUM; NON-HODGKINS-LYMPHOMA; QUALITY-OF-LIFE; PHASE-III TRIAL; CLINICAL-TRIAL; COMBINATION CHEMOTHERAPY; IMMUNE RECONSTITUTION AB Background Kaposi's sarcoma remains the most common cancer in Sub-Saharan Africa and the second most common cancer in HIV-infected patients worldwide. Since the introduction of highly active antiretroviral therapy (HAART), there has been a decline in its incidence. However, Kaposi's sarcoma continues to be diagnosed in HIV-infected patients. Objectives To assess the added advantage of chemotherapy plus HAART compared to HAART alone; and the advantages of different chemotherapy regimens in HAART and HAART naive HIV infected adults with severe or progressive Kaposi's sarcoma. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and, GATEWAY, the WHO Clinical Trials Registry Platform and the US National Institutes of Health's ClinicalTrials.gov for ongoing trials and the Aegis archive of HIV/AIDS for conference abstracts. An updated search was conducted in July 2014. Selection criteria Randomised trials and observational studies evaluating the effects of any chemotherapeutic regimen in combination with HAART compared to HAART alone, chemotherapy versus HAART, and comparisons between different chemotherapy regimens. Data collection and analysis Two review authors assessed the studies independently and extracted outcome data. We used the risk ratio (RR) with a 95% confidence interval (CI) as the measure of effect. We did not conduct meta-analysis as none of the included trials assessed identical chemotherapy regimens. Main results We included six randomised trials and three observational studies involving 792 HIV-infected adults with severe Kaposi's sarcoma. Seven studies included patients with a mix of mild to moderate (T0) and severe (T1) Kaposi's sarcoma. However, this review was restricted to the subset of participants with severe Kaposi's sarcoma disease. Studies comparing HAART plus chemotherapy to HAART alone showed the following: one trial comparing HAART plus doxorubicin, bleomycin and vincristine (ABV) to HAART alone showed a significant reduction in disease progression in the HAART plus ABV group (RR 0.10; 95% CI 0.01 to 0.75, 100 participants); there was no statistically significant reduction in mortality and no difference in adverse events. A cohort study comparing liposomal anthracyclines plus HAART to HAART alone showed a non-statistically significant reduction in Kaposi's sarcoma immune reconstitution inflammatory syndrome in patients that received HAART plus liposomal anthracyclines (RR 0.49; 95% CI 0.16 to 1.55, 129 participants). Studies comparing HAART plus chemotherapy to HAART plus a different chemotherapy regimen showed the following: one trial involving 49 participants and comparing paclitaxel versus pegylated liposomal doxorubicin in patients on HAART showed no difference in disease progression. Another trial involving 46 patients and comparing pegylated liposomal doxorubicin versus liposomal daunorubicin showed no participants with progressive Kaposi's sarcoma disease in either group. Studies comparing different chemotherapy regimens in patients from the pre-HAART era showed the following: in the single RCT comparing liposomal daunorubicin to ABV, there was no significant difference with the use of liposomal daunorubicin compared to ABV in disease progression (RR 0.78; 95% CI 0.34 to 1.82, 227 participants) and overall response rate. Another trial involving 178 participants and comparing oral etoposide versus ABV demonstrated no difference in mortality in either group. A non-randomised trial comparing bleomycin alone to ABV demonstrated a higher median survival time in the ABV group; there was also a non-statistically significant reduction in adverse events and disease progression in the ABV group (RR 11; 95% CI 0.67 to 179.29, 24 participants). An additional non-randomised study showed a non-statistically significant overall mortality benefit from liposomal doxorubicin as compared to conservative management consisting of either bleomycin plus vinblastine, vincristine or single-agent antiretroviral therapy alone (RR 0.93; 95% CI 0.75 to 1.15, 29 participants). The overall quality of evidence can be described as moderate quality. The quality of evidence was downgraded due to the small size of many of the included studies and small number of events. Authors' conclusions The findings from this review suggest that HAART plus chemotherapy may be beneficial in reducing disease progression compared to HAART alone in patients with severe or progressive Kaposi's sarcoma. For patients on HAART, when choosing from different chemotherapy regimens, there was no observed difference between liposomal doxorubicin, liposomal daunorubicin and paclitaxel. C1 [Gbabe, Oluwatoyin F.] Univ Stellenbosch, Fac Med & Hlth Sci, Community Hlth Div, ZA-7505 Cape Town, South Africa. [Okwundu, Charles I.] Univ Stellenbosch, Fac Med & Hlth Sci, Ctr Evidence Based Hlth Care, ZA-7505 Cape Town, South Africa. [Okwundu, Charles I.] South African Med Res Council, South African Cochrane Ctr, Tygerberg, South Africa. [Dedicoat, Martin] Birmingham Heartlands Hosp, Dept Infect, Birmingham B9 5ST, W Midlands, England. [Freeman, Esther E.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Freeman, Esther E.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Gbabe, OF (reprint author), Univ Stellenbosch, Fac Med & Hlth Sci, Community Hlth Div, Francie van Zijl Dr, ZA-7505 Cape Town, South Africa. EM gbabetoyin@yahoo.com FU Centre for Evidence-based Health Care, Stellenbosch University, South Africa; Harry Crossley Foundation, South Africa; World Health Organization, Switzerland; National Institutes of Health, USA FX Internal sources; Centre for Evidence-based Health Care, Stellenbosch University, South Africa.; External sources; Harry Crossley Foundation, South Africa.; World Health Organization, Switzerland.; National Institutes of Health, USA. NR 78 TC 8 Z9 8 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X EI 1361-6137 J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2014 IS 9 AR CD003256 DI 10.1002/14651858.CD003256.pub2 PG 76 WC Medicine, General & Internal SC General & Internal Medicine GA AY5YT UT WOS:000347645800016 PM 25221796 ER PT J AU Moazzami, K Moazzami, B Roohi, A Nedjat, S Dolmatova, E AF Moazzami, Kasra Moazzami, Bobak Roohi, Aria Nedjat, Saharnaz Dolmatova, Elena TI Local intramuscular transplantation of autologous mononuclear cells for critical lower limb ischaemia SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review DE Alprostadil [administration & dosage]; Amputation [utilization]; Ankle Brachial Index; BoneMarrow Transplantation [methods]; Granulocyte Colony-Stimulating Factor [administration & dosage]; Injections, Intramuscular; Ischemia [etiology; therapy]; Leg [blood supply]; Leukocytes, Mononuclear [transplantation]; Pain Measurement; Peripheral Vascular Diseases [complications]; Randomized Controlled Trials as Topic; Transplantation, Autologous; Vasodilator Agents [administration & dosage]; Adult; Humans AB Background Peripheral arterial disease is a major health problem, and in about 1% to 2% of patients the disease progresses to critical limb ischaemia (CLI). In a substantial number of patients with CLI, no effective treatment option other than amputation is available and around a quarter of these patients will require a major amputation during the following year. This is an update of the review first published in 2011. Objectives To determine the effectiveness and safety of local intramuscular transplantation of autologous adult bone marrow mononuclear cells (BMMNCs) as a treatment for critical limb ischaemia (CLI). Search methods For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched February 2014) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 1). Selection criteria We included all randomised controlled trials of CLI in which participants were randomly allocated to intramuscular administration of autologous adult BMMNCs or control (either no intervention or conventional conservative therapy). We excluded studies on patients with intermittent claudication. Data collection and analysis Two authors independently selected trials, assessed trials for eligibility and methodological quality, and extracted data. Disagreements were resolved by consensus or by the third author. Main results Only two small studies, with a combined total of 57 participants, met our inclusion criteria and were finally included. They were classified as having a moderate risk of bias with unclear issues regarding their methods, and according to the GRADE approach, the overall quality of the evidence would be considered as moderate. In one study the effects of intramuscular injections of BMMNCs in the ischaemic lower limbs of patients with CLI were compared with control (standard conservative treatment). No deaths were reported and no significant difference was observed between the two groups for either pain (P = 0.37) or the ankle brachial index (ABI) parameter. However, the treatment group showed a significantly smaller proportion of participants undergoing amputation compared with the control group (P = 0.026). In the other study, following subcutaneous injections of granulocyte colony-stimulating factor (G-CSF) for five days, peripheral blood derived mononuclear cells were collected and then transplanted by intramuscular injections into ischaemic lower limbs. The effects were compared with daily intravenous prostaglandin E1 injections (control group). No deaths were reported. Pain reduction was greater in the treatment group than in the control group (P < 0.001) as was increase in ABI (mean increase 0.13 versus 0.02, P < 0.01). The treatment group experienced a statistically significant increase in pain-free walking distance (PFWD) compared with the control group (mean increase 306.4 m versus 78.6 m, P = 0.007). A smaller proportion of participants underwent amputation in the treatment group compared with the control group (0% versus 36%, P = 0.007). Authors' conclusions The data from the published trials suggest that there is insufficient evidence to support this treatment. These results were based on only two trials which had a very small number of participants. Therefore evidence from larger randomised controlled trials is needed in order to provide adequate statistical power to assess the role of intramuscular mononuclear cell implantation in patients with CLI. C1 [Moazzami, Kasra; Dolmatova, Elena] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr CVRC, 149 St, Charlestown, MA USA. [Moazzami, Bobak; Roohi, Aria] Babol Univ Med Sci, Student Res Comm, Babol Sar, Iran. [Nedjat, Saharnaz] Univ Tehran Med Sci, Sch Publ Hlth, Dept Epidemiol & Biostat, Tehran, Iran. [Nedjat, Saharnaz] Tehran Univ Med Sci, KURC, Tehran, Iran. RP Moazzami, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr CVRC, 149 St, Charlestown, MA USA. EM moazzami.kasra@mgh.harvard.edu FU Chief Scientist Office, Scottish Government Health Directorates, The Scottish Government, UK; Chief Scientist Office FX External sources; Chief Scientist Office, Scottish Government Health Directorates, The Scottish Government, UK.; The PVD Group editorial base is supported by the Chief Scientist Office. NR 71 TC 4 Z9 4 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X EI 1361-6137 J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2014 IS 12 AR CD008347 DI 10.1002/14651858.CD008347.pub3 PG 28 WC Medicine, General & Internal SC General & Internal Medicine GA V43SL UT WOS:000209701000016 PM 25525690 ER PT J AU Hoggatt, KJ Greenland, S AF Hoggatt, Katherine J. Greenland, Sander TI Extending Organizational Schema for Causal Effects SO EPIDEMIOLOGY LA English DT Editorial Material ID MARGINAL STRUCTURAL MODELS; LOGISTIC-REGRESSION; INFERENCE; INTERFERENCE; COLLAPSIBILITY; LOST; BIAS; TOOL C1 [Hoggatt, Katherine J.] VA Greater Los Angeles Hlth Serv Res & Dev, Ctr Excellence, Sepulveda, CA USA. [Hoggatt, Katherine J.; Greenland, Sander] UCLA Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA USA. [Greenland, Sander] UCLA Coll Letters & Sci, Dept Stat, Los Angeles, CA USA. RP Hoggatt, KJ (reprint author), VA HSR&D Ctr Excellence Study Healthcare Provider, 16111 Plummer St 152, Sepulveda, CA 91343 USA. EM khoggatt@ucla.edu NR 42 TC 6 Z9 6 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1044-3983 EI 1531-5487 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 2014 VL 25 IS 1 BP 98 EP 102 DI 10.1097/EDE.0000000000000023 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 268XW UT WOS:000328205200016 PM 24296927 ER PT J AU Gray, KE Schiff, MA Fitzpatrick, AL Kimura, M Aviv, A Starr, JR AF Gray, Kristen E. Schiff, Melissa A. Fitzpatrick, Annette L. Kimura, Masayuki Aviv, Abraham Starr, Jacqueline R. TI Leukocyte Telomere Length and Age at Menopause SO EPIDEMIOLOGY LA English DT Article ID MINI-MENTAL STATE; CARDIOVASCULAR HEALTH; CANCER-RISK; WOMEN; LIFE; ADULTS; ASSOCIATIONS; DISEASE; TISSUES; HUMANS AB Background: Telomere length is a marker of cellular aging that varies with the individual, is inherited, and is highly correlated across somatic cell types within persons. Interindividual variability of telomere length may partly explain differences in reproductive aging rates. We examined whether leukocyte telomere length was associated with menopausal age. Methods: We evaluated the relationship between leukocyte telomere length and age at natural menopause in 486 white women 65 years of age. We fit linear regression models adjusted for age, income, education, body mass index, physical activity, smoking, and alcohol intake. We repeated the analysis in women with surgical menopause. We also performed sensitivity analyses excluding women (1) with unilateral oophorectomy, (2) who were nulliparous, or (3) reporting menopausal age <40 years, among other exclusions. Results: For every 1-kb increase in leukocyte telomere length, average age at natural menopause increased by 10.2 months (95% confidence interval = 1.3 to 19.0). There was no association among 179 women reporting surgical menopause. In all but one sensitivity analysis, the association between leukocyte telomere length and age at menopause became stronger. However, when excluding women with menopausal age <40 years, the association decreased to 7.5 months (-0.4 to 15.5). Conclusions: Women with the longest leukocyte telomere length underwent menopause 3 years later than those with the shortest leukocyte telomere length. If an artifact, an association would likely also have been observed in women with surgical menopause. If these results are replicated, leukocyte telomere length may prove to be a useful predictor of age at menopause. C1 [Gray, Kristen E.; Schiff, Melissa A.; Fitzpatrick, Annette L.; Starr, Jacqueline R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Kimura, Masayuki; Aviv, Abraham] Univ Med & Dent New Jersey, New Jersey Med Sch, Ctr Human Dev & Aging, Newark, NJ 07103 USA. [Starr, Jacqueline R.] Forsyth Inst, Ctr Clin & Translat Res, Cambridge, MA 02142 USA. [Starr, Jacqueline R.] Harvard Univ, Sch Dent Med, Dept Oral Hlth Policy & Epidemiol, Boston, MA 02115 USA. RP Starr, JR (reprint author), Forsyth Inst, Ctr Clin & Translat Res, 245 1st St, Cambridge, MA 02142 USA. EM jstarr@forsyth.org FU NICHD [T32 HD052462]; NHLBI [1 R01 HL80698-01, HHSN268201200036C, N01-HC-85239, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, HL080295]; NIA [AG-023629, AG-15928, AG-20098, AG-027058] FX This publication was made possible by grant number T32 HD052462 from NICHD and grant 1 R01 HL80698-01 from NHLBI. This research was also supported by contracts HHSN268201200036C, N01-HC-85239, N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, and grant HL080295 from NHLBI, with additional contribution from NINDS. Additional support was provided through AG-023629, AG-15928, AG-20098, and AG-027058 from the NIA. NR 43 TC 13 Z9 13 U1 2 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 EI 1531-5487 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 2014 VL 25 IS 1 BP 139 EP 146 DI 10.1097/EDE.0000000000000017 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 268XW UT WOS:000328205200023 PM 24213145 ER PT J AU Bergman, J Litwin, MS AF Bergman, Jonathan Litwin, Mark S. TI The Henderson-Hasselbalch Equation for Urologists SO EUROPEAN UROLOGY LA English DT Editorial Material ID QUALITY-OF-LIFE; RADICAL PROSTATECTOMY; FOLLOW-UP; MORTALITY; TRIAL C1 [Bergman, Jonathan; Litwin, Mark S.] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA 90095 USA. [Bergman, Jonathan] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Bergman, Jonathan] Univ Calif Los Angeles, Robert Wood Johnson Fdn Clin Scholars Program, Los Angeles, CA 90095 USA. [Litwin, Mark S.] Univ Calif Los Angeles, Dept Hlth Serv, Los Angeles, CA 90095 USA. [Litwin, Mark S.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. RP Litwin, MS (reprint author), Univ Calif Los Angeles, Dept Urol, Box 951738, Los Angeles, CA 90095 USA. EM mlitwin@mednet.ucla.edu NR 10 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD JAN PY 2014 VL 65 IS 1 BP 48 EP 49 DI 10.1016/j.eururo.2012.12.021 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 262VR UT WOS:000327766500015 PM 23291297 ER PT J AU Nanda, A Chen, MH Moran, BJ Braccioforte, MH Dosoretz, D Salenius, S Katin, M Ross, R D'Amico, AV AF Nanda, Akash Chen, Ming-Hui Moran, Brian J. Braccioforte, Michelle H. Dosoretz, Daniel Salenius, Sharon Katin, Michael Ross, Rudi D'Amico, Anthony V. TI Neoadjuvant Hormonal Therapy Use and the Risk of Death in Men with Prostate Cancer Treated with Brachytherapy Who Have No or at Least a Single Risk Factor for Coronary Artery Disease SO EUROPEAN UROLOGY LA English DT Article DE Prostate cancer; Neoadjuvant hormonal therapy; Brachytherapy; Risk factors; Coronary artery disease; Diabetes mellitus; Hypercholesterolemia; Hypertension ID ANDROGEN-DEPRIVATION THERAPY; RANDOMIZED CONTROLLED-TRIAL; ORAL-CONTRACEPTIVE USE; MYOCARDIAL-INFARCTION; RADIATION-ONCOLOGY; HEART-DISEASE; RADIOTHERAPY; SUPPRESSION; MORTALITY AB Background: Neoadjuvant hormone therapy (NHT) use is associated with an increased risk of all-cause mortality (ACM) in men with a history of coronary artery disease (CAD)induced congestive heart failure (CHF) or myocardial infarction (MI). However, its effect in men with no or at least a single risk factor for CAD stratified by prostate cancer (PCa) aggressiveness is unknown. Objective: To assess whether NHT use affects the risk of ACM in men with low-, intermediate-, and high-risk PCa treated with brachytherapy who have no or at least a single risk factor for CAD. Design, setting, and participants: This retrospective study cohort consisted of 5411 men with low-risk PCa (prostate-specific antigen [PSA] <10 ng/ml, Gleason score 6, and clinical stage T1-T2a); 4365 men with intermediate-risk PCa (PSA 10-20 ng/ml or Gleason score <8 or clinical stage = 80 years) are disproportionally affected by acute ischemic stroke. They account for a third of hospital stroke admissions, but two-thirds of overall stroke-related morbidity and mortality. There is some evidence of clinical benefit in treating selected very elderly patients with intravenous thrombolysis (IVT). For very elderly patients ineligible or non-responsive to IVT, intra-arterial therapy (IAT) may have promise in improving clinical outcome. However, its unequivocal efficacy in the general population remains to be proven in randomized trials. Small cohort studies reveal that the rate of good clinical outcome for very elderly patients after IAT is highly variable, ranging from 0 to 28%. In addition, they experience higher rates of futile reperfusion than younger patients. Thus, it is imperative to understand the factors that impact on clinical outcome in very elderly patients after IAT. The aim of this review is to examine the factors that may be responsible for the heterogeneous clinical response of the very elderly to IAT. This will allow the reader to integrate the current available evidence to individualize intra-arterial stroke therapy in very elderly patients. Placing emphasis on pre-stroke independent living, smaller infarct core size, short procedure times, and avoiding general anesthesia where feasible, will help improve rates of good clinical outcome. C1 [Chandra, Ronil V.] Monash Univ, Monash Hlth, Diagnost & Intervent Neuroradiol, Clayton Rd, Melbourne, Vic 3168, Australia. [Leslie-Mazwi, Thabele M.; Mehta, Brijesh P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendovasc & Neurol Crit Care, Boston, MA USA. [Yoo, Albert J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendovasc & Neuroradiol, Boston, MA USA. [Simonsen, Claus Z.] Aarhus Univ Hosp, Dept Neurol, DK-8000 Aarhus, Denmark. RP Chandra, RV (reprint author), Monash Univ, Monash Hlth, Diagnost & Intervent Neuroradiol, Clayton Rd, Melbourne, Vic 3168, Australia. EM ronil.chandra@monashhealth.org NR 60 TC 2 Z9 2 U1 1 U2 1 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 2014 VL 5 AR 60 DI 10.3389/fneur.2014.00060 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V42QW UT WOS:000209629300060 PM 24808887 ER PT J AU Egyhazi, R Fregni, F Bravo, GL Trinh, NHT Ryan, CM Schneider, JC AF Egyhazi, Rachel Fregni, Felipe Bravo, Gabriela L. Trinh, Nhi-Ha T. Ryan, Colleen M. Schneider, Jeffrey C. TI Chronic pain following physical and emotional trauma: The Station nightclub fire SO FRONTIERS IN NEUROLOGY LA English DT Article DE fire; burn; graft; pain; depression AB Objective: The purpose of this study was to evaluate factors associated with chronic pain in survivors of a large fire, including those with and without burn injury. Methods:This study employed a survey-based cross-sectional design to evaluate data from survivors of The Station nightclub fire. The primary outcome measure was the presence and severity of pain. Multiple linear regressions with a stepwise approach were used to examine relationships among variables. Variables considered included age, gender, marital status, burn injury, total body surface area, skin graft, pre-morbid employment, time off work, return to same employment, depression (Beck depression inventory, BDI), and post-traumatic stress (impact of event scale - revised). Results: Of 104 fire survivors, 27% reported pain at least 28 months after the event. Multiple factors associated with pain were assessed in the univariate analysis but only age (p = 0.012), graft (p = 0.009), and BDI score (p < 0.001) were significantly associated with pain in the multiple regression model. Discussion: A significant number of fire survivors with and without burn injuries experienced chronic pain. Depth of burn and depression were significantly associated with pain outcome. Pain management should address both physical and emotional risk factors in this population. C1 [Egyhazi, Rachel; Fregni, Felipe; Schneider, Jeffrey C.] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02115 USA. [Fregni, Felipe; Bravo, Gabriela L.] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Neuromodulat Ctr, Boston, MA 02115 USA. [Trinh, Nhi-Ha T.] Massachusetts Gen Hosp, Dept Psychiat, Depress & Clin Res Program, Boston, MA 02114 USA. [Ryan, Colleen M.] Massachusetts Gen Hosp, Sumner Redstone Burn Ctr, Dept Surg, Boston, MA 02114 USA. [Ryan, Colleen M.; Schneider, Jeffrey C.] Shriners Hosp Children, Boston, MA USA. RP Fregni, F (reprint author), Spaulding Rehabil Hosp, Neuromodulat Ctr, Dept Phys Med & Rehabil, 300 1st Ave, Charlestown, MA 02129 USA. EM ffregni@partners.org FU Department of Education, NIDRR [H133A120034] FX Funding sources: the content of this manuscript was developed under a grant from the Department of Education, NIDRR grant number H133A120034. However, this content does not necessarily represent the policy of the Department of Education, and endorsement by the Federal Government should not be assumed. NR 50 TC 0 Z9 0 U1 3 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 2014 VL 5 DI 10.3389/fneur.2014.00086 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V42QW UT WOS:000209629300085 ER PT J AU Elder, GA Stone, JR Ahlers, ST AF Elder, Gregory A. Stone, James R. Ahlers, Stephen T. TI Effects of low-level east exposure on the nervous system: is there really a controversy? SO FRONTIERS IN NEUROLOGY LA English DT Review DE animal models; blast; human studies; post-traumatic stress disorder; traumatic brain injury AB High-pressure blast waves can cause extensive CNS injury in human beings. However, in combat settings, such as Iraq and Afghanistan, lower level exposures associated with mild traumatic brain injury (mTBI) or subclinical exposure have been much more common. Yet controversy exists concerning what traits can be attributed to low-level blast, in large part due to the difficulty of distinguishing blast-related mTBI from post-traumatic stress disorder (PTSD). We describe how TBI is defined in human beings and the problems posed in using current definitions to recognize blast-related mTBI. We next consider the problem of applying definitions of human mTBI to animal models, in particular that TBI severity in human beings is defined in relation to alteration of consciousness at the time of injury, which typically cannot be assessed in animals. However, based on outcome assessments, a condition of "low-level" blast exposure can be defined in animals that likely approximates human mTBI or subclinical exposure. We review blast injury modeling in animals noting that inconsistencies in experimental approach have contributed to uncertainty over the effects of low-level blast. Yet, animal studies show that low-level blast pressure waves are transmitted to the brain. In brain, low-level blast exposures cause behavioral, biochemical, pathological, and physiological effects on the nervous system including the induction of PTSD-related behavioral traits in the absence of a psychological stressor. We review the relationship of blast exposure to chronic neurodegenerative diseases noting the paradoxical lowering of Abeta by blast, which along with other observations suggest that blast-related TBI is pathophysiologically distinct from non-blast TBI. Human neuroimaging studies show that blast-related mTBI is associated with a variety of chronic effects that are unlikely to be explained by co-morbid PTSD. We conclude that abundant evidence supports low-level blast as having long-term effects on the nervous system. C1 [Elder, Gregory A.] James J Peters Dept Vet Affairs Med Ctr, Neurol Serv, Bronx, NY 10468 USA. [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. [Elder, Gregory A.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. [Stone, James R.] Univ Virginia, Dept Radiol, Charlottesville, VA USA. [Stone, James R.] Univ Virginia, Dept Neurosurg, Charlottesville, VA USA. [Ahlers, Stephen T.] Naval Med Res Ctr, Dept Neurotrauma, Operat & Undersea Med Directorate, Silver Spring, MD USA. RP Elder, GA (reprint author), James J Peters Dept Vet Affairs Med Ctr, Neurol Serv 3E16, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM gregory.elder@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service [1I01RX000179-01, 1I01RX000996-01] FX The authors have received research support from the Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service Awards 1I01RX000179-01 and 1I01RX000996-01. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the U.S. Government. Stephen T. Ahlers: I am a military service member (or employee of the U.S. Government). This work was prepared as part of my official duties. Title 17 U.S.C. 105 provides that copyright protection under this title is not available for any work of the United States Government. Title 17 U.S.C. 101 defines a U.S. Government work as a work prepared by a military service member or employee of the U.S. Government as part of that person's official duties. NR 212 TC 15 Z9 15 U1 0 U2 2 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 2014 VL 5 AR 269 DI 10.3389/fneur.2014.00269 PG 22 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V42QW UT WOS:000209629300252 PM 25566175 ER PT J AU Gokbayrak, NS Piryatinsky, I Gavett, RA Ahmed, OJ AF Goekbayrak, N. Simay Piryatinsky, Irene Gavett, Rebecca A. Ahmed, Omar J. TI Mixed effects of deep brain stimulation on depressive symptomatology in Parkinson's disease: a review of randomized clinical trials SO FRONTIERS IN NEUROLOGY LA English DT Review DE Parkinson's disease; deep brain stimulation; depression; DBS; randomized clinical trial AB Although similar to 50% of patients with Parkinson's disease (PD) experience depression, treatment for this important and debilitating comorbidity is relatively understudied. Deep brain stimulation (DBS) has been increasingly utilized for the management of tremors in progressive PD. Several preliminary studies have shown the potential benefit of DBS for non-motor PD symptoms such as depression. Here, we critically evaluate seven recent randomized clinical trials of the effectiveness of DBS in reducing depressive symptomatology among individuals with PD. Findings are mixed for the effectiveness of DBS as a treatment for depression in PD. Our review suggests that this is due, in large part, to the anatomical and methodological variation across the DBS studies. We provide a comprehensive discussion of these variations and highlight the need to conduct larger, more controlled studies aimed specifically at evaluating the treatment of depression in PD patients. C1 [Goekbayrak, N. Simay] Univ Rhode Isl, Dept Psychol, Kingston, RI 02881 USA. [Piryatinsky, Irene; Gavett, Rebecca A.] Brown Univ, Warren Alpert Med Sch, Butler Hosp, Memory & Aging Program, Providence, RI 02912 USA. [Ahmed, Omar J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. RP Gokbayrak, NS (reprint author), 10 Chafee Rd,Chafee Hall, Kingston, RI 02881 USA. EM simaygokbayrak@gmail.com NR 62 TC 1 Z9 1 U1 0 U2 2 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 2014 VL 5 AR 154 DI 10.3389/fneur.2014.00154 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V42QW UT WOS:000209629300147 PM 25157240 ER PT J AU King, S Wang, J Priesol, AJ Lewis, RF AF King, Susan Wang, Joanne Priesol, Adrian J. Lewis, Richard F. TI Central integration of canal and otolith signals is abnormal in vestibular migraine SO FRONTIERS IN NEUROLOGY LA English DT Article DE vestibular; migraine; cerebellum; perception; oculomotor AB Vestibular migraine (VM), a common cause of vestibular symptoms within the general population, is a disabling and poorly understood form of dizziness. We sought to examine the underlying pathophysiology of VM with three studies, which involved the central synthesis of canal and otolith cues, and present preliminary results from each of these studies: (1) VM patients appear to have reduced motion perception thresholds when canal and otolith signals are modulated in a co-planar manner during roll tilt; (2) percepts of roll tilt appear to develop more slowly in VM patients than in control groups during a centrifugation paradigm that presents conflicting, orthogonal canal and otolith cues; and (3) eye movement responses appear to be different in VM patients when studied with a post-rotational tilt paradigm, which also presents a canal otolith conflict, as the shift of the eye's rotational axis was larger in VM and the relationship between the axis shift and tilt suppression of the vestibulo-ocular reflex differed in VM patients relative to control groups. Based on these preliminary perceptual and eye movement results obtained with three different motion paradigms, we present a hypothesis that the integration of canal and otolith signals by the brain is abnormal in VM and that this abnormality could be cerebellar in origin. We provide potential mechanisms that could underlie these observations, and speculate that one of more of these mechanisms contributes to the vestibular symptoms and motion intolerance that are characteristic of the VM syndrome. C1 [King, Susan] Boston Univ, Boston, MA 02215 USA. [King, Susan; Lewis, Richard F.] Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. [Wang, Joanne] Brown Univ, Sch Med, Providence, RI 02912 USA. [Priesol, Adrian J.; Lewis, Richard F.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Lewis, Richard F.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Lewis, RF (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM richard_lewis@meei.harvard.edu FU NIDCD NIH HHS [R01 DC012528] NR 44 TC 10 Z9 10 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 2014 VL 5 AR 233 DI 10.3389/fneur.2014.00233 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V42QW UT WOS:000209629300219 PM 25426098 ER PT J AU Stapleton-Kotloski, JR Kotloski, RJ Boggs, JA Popli, G O'Donovan, CA Couture, DE Cornell, C Godwin, DW AF Stapleton-Kotloski, Jennifer R. Kotloski, Robert J. Boggs, Jane A. Popli, Gautam O'Donovan, Cormac A. Couture, Daniel E. Cornell, Cassandra Godwin, Dwayne W. TI Localization of interictal epileptiorm activity using magnetoencephalography with synthetic aperture magnetometry in patients with a vagus nerve stimulator SO FRONTIERS IN NEUROLOGY LA English DT Article DE magnetoencephalography; synthetic aperture magnetometry; vagus nerve stimulator; epilepsy; epilepsy surgical evaluation AB Magnetoencephalography (MEG) provides useful and non-redundant information in the evaluation of patients with epilepsy, and in particular, during the pre-surgical evaluation of pharmaco-resistant epilepsy. Vagus nerve stimulation (VNS) is a common treatment for pharmaco-resistant epilepsy. However, interpretation of MEG recordings from patients with a VNS is challenging due to the severe magnetic artifacts produced by the VNS. We used synthetic aperture magnetometry (g2) [SAM(g2)], an adaptive beamformer that maps the excessive kurtosis, to map interictal spikes to the coregistered MRI image, despite the presence of contaminating VNS artifact. We present a series of eight patients with a VNS who underwent MEG recording. Localization of interictal epileptiform activity by SAM(g2) is compared to invasive electrophysiologic monitoring and other localizing approaches. While the raw MEG recordings were uninterpretable, analysis of the recordings with SAM(g2) identified foci of peak kurtosis and source signal activity that was unaffected by the VNS artifact. SAM(g2) analysis of MEG recordings in patients with a VNS produces interpretable results and expands the use of MEG for the pre-surgical evaluation of epilepsy. C1 [Stapleton-Kotloski, Jennifer R.; Boggs, Jane A.; Popli, Gautam; O'Donovan, Cormac A.; Cornell, Cassandra; Godwin, Dwayne W.] Wake Forest Univ, Bowman Gray Sch Med, Dept Neurol, 1 Med Ctr Blvd, Winston Salem, NC 27103 USA. [Kotloski, Robert J.] William S Middleton Mem Vet Adm Med Ctr, Dept Neurol, Madison, WI USA. [Kotloski, Robert J.] Univ Wisconsin, Dept Neurol, Sch Med & Publ Hlth, Madison, WI USA. [Couture, Daniel E.] Wake Forest Univ, Sch Med, Dept Neurosurg, Winston Salem, NC USA. [Godwin, Dwayne W.] Wake Forest Univ, Sch Med, Dept Neurobiol & Anat, Winston Salem, NC USA. RP Stapleton-Kotloski, JR (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Neurol, 1 Med Ctr Blvd, Winston Salem, NC 27103 USA. EM jstaplet@wakehealth.edu FU NIAAA [T32 AA-007565, RO1AA016852]; Wake Forest University School of Medicine Translational Science Institute Salisbury Veterans Administration Joint Pilot Award FX We would like to thank Valerie Woodard, Tanya Lassila, Scott Kuhn, Melissa Brown, and Sandra Griffin for their help and assistance. We would also like to thank the Epilepsy Center of Excellence for their support of this project. This work was funded by NIAAA T32 AA-007565 (Jennifer Rebecca Stapleton-Kotloski), Wake Forest University School of Medicine Translational Science Institute Salisbury Veterans Administration Joint Pilot Award (Jennifer Rebecca Stapleton-Kotloski, Dwayne W. Godwin), and NIAAA RO1AA016852 (Dwayne W. Godwin). NR 53 TC 0 Z9 0 U1 1 U2 1 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 2014 VL 5 AR 244 DI 10.3389/fneur.2014.00244 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V42QW UT WOS:000209629300230 PM 25505894 ER PT J AU Guizzetti, M Zhang, XL Goeke, C Gavin, DP AF Guizzetti, Marina Zhang, Xiaolu Goeke, Calla Gavin, David P. TI Glia and neurodevelopment: focus on fetal alcohol spectrum disorders SO FRONTIERS IN PEDIATRICS LA English DT Review DE glia; astrocytes; oligodendrocytes; microglia; fetal alcohol spectrum disorders; neurodevelopment AB During the last 20 years, new and exciting roles for glial cells in brain development have been described. Moreover, several recent studies implicated glial cells in the pathogenesis of neurodevelopmental disorders including Down syndrome, Fragile X syndrome, Rett Syndrome, Autism Spectrum Disorders, and Fetal Alcohol Spectrum Disorders (FASD). Abnormalities in glial cell development and proliferation and increased glial cell apoptosis contribute to the adverse effects of ethanol on the developing brain and it is becoming apparent that the effects of fetal alcohol are due, at least in part, to effects on glial cells affecting their ability to modulate neuronal development and function. The three major classes of glial cells, astrocytes, oligodendrocytes, and microglia as well as their precursors are affected by ethanol during brain development. Alterations in glial cell functions by ethanol dramatically affect neuronal development, survival, and function and ultimately impair the development of the proper brain architecture and connectivity. For instance, ethanol inhibits astrocyte-mediated neuritogenesis and oligodendrocyte development, survival and myelination; furthermore, ethanol induces microglia activation and oxidative stress leading to the exacerbation of ethanol-induced neuronal cell death. This review article describes the most significant recent findings pertaining the effects of ethanol on glial cells and their significance in the pathophysiology of FASD and other neurodevelopmental disorders. C1 [Guizzetti, Marina; Zhang, Xiaolu; Goeke, Calla; Gavin, David P.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. [Guizzetti, Marina; Zhang, Xiaolu; Goeke, Calla; Gavin, David P.] US Dept Vet Affairs, Jesse Brown VA Med Ctr, Chicago, IL USA. [Guizzetti, Marina] Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. RP Guizzetti, M (reprint author), Jesse Brown VA Med Ctr, Res & Dev Sect, M-C 151,820 South Damen Ave, Chicago, IL 60612 USA. EM mguizzetti@psych.uic.edu FU National Institute of Alcoholism and Alcohol Abuse [AA021876] FX This study was supported in part by grant AA021876 from the National Institute of Alcoholism and Alcohol Abuse. The authors are extremely grateful to Mr. Jeff Frkonja for the graphic design of Figures 1, 3, and 4. NR 171 TC 19 Z9 20 U1 0 U2 1 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 2014 VL 2 AR 123 DI 10.3389/fped.2014.00123 PG 12 WC Pediatrics SC Pediatrics GA V46PX UT WOS:000209897200122 PM 25426477 ER PT J AU Ingelfinger, JR AF Ingelfinger, Julie R. TI A remembrance of Mary Ellen Avery, M.D. SO FRONTIERS IN PEDIATRICS LA English DT Biographical-Item DE mentors; mentoring; pediatrics; leadership; commentary C1 [Ingelfinger, Julie R.] Massachusetts Gen Hosp, MassGen Hosp Children, Pediat Nephrol, Boston, MA 02114 USA. [Ingelfinger, Julie R.] Harvard Med Sch, Dept Pediat, Boston, MA USA. RP Ingelfinger, JR (reprint author), Massachusetts Gen Hosp, MassGen Hosp Children, Pediat Nephrol, Boston, MA 02114 USA. EM jingelfinger@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 2296-2360 J9 FRONT PEDIATR JI Front. Pediatr. PY 2014 VL 2 AR 19 DI 10.3389/fped.2014.00019 PG 2 WC Pediatrics SC Pediatrics GA V46PX UT WOS:000209897200019 PM 24795869 ER PT J AU Nott, CR Neptune, RR Kautz, SA AF Nott, C. R. Neptune, R. R. Kautz, S. A. TI Relationships between frontal-plane angular momentum and clinical balance measures during post-stroke hemiparetic walking SO GAIT & POSTURE LA English DT Article DE Stability; Gait; Dynamic balance; Hemiparesis; Clinical measures ID DYNAMIC GAIT INDEX; ASSESSMENT TOOLS; OLDER-ADULTS; COMMUNITY; STROKE; INDIVIDUALS; FALLS; RELIABILITY; TREADMILL; VALIDITY AB Stroke has significant impact on dynamic balance during locomotion, with a 73% incidence rate for falls post-stroke. Current clinical assessments often rely on tasks and/or questionnaires that relate to the statistical probability of falls and provide little insight into the mechanisms that impair dynamic balance. Current quantitative measures that assess medial-lateral balance performance do not consider the angular motion of the body, which can be particularly impaired after stroke. Current control methods in bipedal robotics rely on the regulation of angular momentum (H) to maintain dynamic balance during locomotion. This study tests whether frontal-plane H is significantly correlated to clinical balance tests that could be used to provide a detailed assessment of medial-lateral balance impairments in hemiparetic gait. H was measured in post-stroke (n = 48) and control (n = 20) subjects. Post-stroke there were significant negative relationships between the change in frontal-plane H during paretic single-leg stance and two clinical tests: the Dynamic Gait Index (DGI) (r = -0.57, p < 0.001) and the Berg Balance Scale (BBS) (r = -0.54, p < 0.001). Control subjects showed timely regulation of frontal-plane H during the first half of single-leg stance, with the level of regulation depending on the initial magnitude. In contrast, the post-stroke subjects who made poorer adjustments to frontal-plane H during initial paretic leg single stance exhibited lower DGI and BBS scores (r = 0.45, p = 0.003). We conclude that H is a promising balance indicator during steady-state hemiparetic walking and that paretic single-leg stance is a period with higher instability for stroke patients. Published by Elsevier B.V. C1 [Nott, C. R.; Kautz, S. A.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29403 USA. [Neptune, R. R.] Univ Texas Austin, Dept Mech Engn, Austin, TX 78712 USA. [Kautz, S. A.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Kautz, SA (reprint author), Med Univ S Carolina, Dept Hlth Sci & Res, 77 President St, Charleston, SC 29403 USA. EM kautz@musc.edu OI Kautz, Steven/0000-0003-3151-8235 FU NIH [R01 HD46820] FX Supported by NIH Grant R01 HD46820. NR 32 TC 10 Z9 10 U1 5 U2 18 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0966-6362 EI 1879-2219 J9 GAIT POSTURE JI Gait Posture PD JAN PY 2014 VL 39 IS 1 BP 129 EP 134 DI 10.1016/j.gaitpost.2013.06.008 PG 6 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA 259QS UT WOS:000327542000023 PM 23820449 ER PT J AU Cameron, M Mazumder, R Murchison, C King, L AF Cameron, Michelle Mazumder, Rajarshi Murchison, Charles King, Laurie TI Mini Balance Evaluation Systems Test in people with multiple sclerosis: Reflects imbalance but may not predict falls SO GAIT & POSTURE LA English DT Letter C1 [Cameron, Michelle] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Cameron, Michelle] Portland VA Med Ctr, Portland, OR USA. [Cameron, Michelle; Mazumder, Rajarshi; Murchison, Charles; King, Laurie] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Cameron, M (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd,L226, Portland, OR 97201 USA. EM cameromi@ohsu.edu NR 2 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0966-6362 EI 1879-2219 J9 GAIT POSTURE JI Gait Posture PD JAN PY 2014 VL 39 IS 1 BP 669 EP 669 DI 10.1016/j.gaitpost.2013.08.009 PG 1 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA 259QS UT WOS:000327542000120 PM 24184138 ER PT S AU Florez, JC Barroso, I AF Florez, Jose C. Barroso, Ines BE Gloyn, AL McCarthy, MI TI Genome-Wide Association Studies of Glycaemic Traits: A MAGICal Journey SO GENETICS IN DIABETES: TYPE 2 DIABETES AND RELATED TRAITS SE Frontiers in Diabetes LA English DT Article; Book Chapter ID CORONARY HEART-DISEASE; PROINSULIN LEVELS; COMMON VARIANTS; HBA(1C) LEVELS; GENETIC-LOCI; TCF7L2; HEMOGLOBIN; INSULIN; RISK; POLYMORPHISMS AB Genome-wide association studies (GWAS) of patients with type 2 diabetes (T2D) and unaffected controls (case-control studies) have been hugely successful in identifying T2D risk loci. In the first 2 years of GWAS, over 13 loci were found to associate with T2D risk, 4-fold more than those identified from previous decades of work. As the first wave of disease-focused GWAS came to an end, and large international meta-analysis consortia began to form, our MAGICal journey began. In 2008, the MAGIC (Meta-Analysis of Glucose and Insulin-related traits Consortium) was established to facilitate meta-analysis of GWAS data of continuous glycaemic traits from persons without diabetes. Our aims were 3-fold: (a) to identify loci influencing glycaemic traits as a way to understand the similarities and differences between loci influencing glucose regulation within the normal physiological range and those affecting pathophysiological states; (b) to identify new loci impacting T2D risk, and (c) to use glycaemic traits to begin to elucidate disease mechanism, i. e. how loci impact biological pathways to promote disease. Here, we describe the approaches used, what we have learned during this journey about the genetic architecture of glycaemic traits and T2D itself, and how we see the future unfolding. (C) 2014 S. Karger AG, Basel C1 [Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Florez, Jose C.] Harvard Med Sch, Dept Med, Boston, MA USA. [Barroso, Ines] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton CB10 1SA, England. [Barroso, Ines] NIHR Cambridge Biomed Res Ctr, Cambridge, England. [Barroso, Ines] Univ Cambridge, Metab Res Labs, Inst Metab Sci, Addenbrookes Hosp, Cambridge, England. RP Barroso, I (reprint author), Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton CB10 1SA, England. EM ib1@sanger.ac.uk NR 22 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0251-5342 BN 978-3-318-02700-6; 978-3-318-02699-3 J9 FRONT DIABETES JI Front.Diabetes PY 2014 VL 23 BP 42 EP 57 DI 10.1159/000362466 D2 10.1159/isbn.978-3-318-02700-6 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BG2UO UT WOS:000387711300005 ER PT S AU Pearson, ER Florez, JC AF Pearson, Ewan R. Florez, Jose C. BE Gloyn, AL McCarthy, MI TI Genetics of Drug Response in Diabetes SO GENETICS IN DIABETES: TYPE 2 DIABETES AND RELATED TRAITS SE Frontiers in Diabetes LA English DT Article; Book Chapter ID CHANNEL SUBUNIT KIR6.2; CATION TRANSPORTER 1; THERAPEUTIC RESPONSE; ACTIVATING MUTATIONS; METFORMIN TREATMENT; PREVENTION PROGRAM; SECONDARY FAILURE; GLYCEMIC CONTROL; INCREASED RISK; COMMON SNPS AB Patients with diabetes differ in how their diabetes responds to treatment. Some individuals can have a marked glycaemic response; others have a poor response. Some have adverse drug reactions (e.g. hypoglycaemia with sulphonylureas, or diarrhoea with metformin), others do not. Diabetes is one of the few disease areas (outside of cancer therapy) where pharmacogenetics is impacting on our understanding of drug mechanism, and on direct clinical care. In this review, we address the complexities of studying drug response in diabetes, and highlight key recent advances both within monogenic diabetes and common type 2 diabetes. (C) 2014 S. Karger AG, Basel C1 [Pearson, Ewan R.] Univ Dundee, Med Res Inst, Div Cardiovasc & Diabet Med, Dundee DD2 9SY, Scotland. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Florez, Jose C.] Harvard Med Sch, Dept Med, Boston, MA USA. [Florez, Jose C.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. RP Pearson, ER (reprint author), Univ Dundee, Med Res Inst, Div Cardiovasc & Diabet Med, Dundee DD2 9SY, Scotland. EM e.z.pearson@dundee.ac.uk NR 48 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0251-5342 BN 978-3-318-02700-6; 978-3-318-02699-3 J9 FRONT DIABETES JI Front.Diabetes PY 2014 VL 23 BP 158 EP 172 DI 10.1159/000362475 D2 10.1159/isbn.978-3-318-02700-6 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BG2UO UT WOS:000387711300014 ER PT J AU Bauer, M Demyttenaere, K El-Khalili, N Thase, ME Papakostas, GI Szamosi, J Earley, WR Eriksson, H AF Bauer, Michael Demyttenaere, Koen El-Khalili, Nizar Thase, Michael E. Papakostas, George I. Szamosi, Johan Earley, Willie R. Eriksson, Hans TI Pooled analysis of adjunct extended-release quetiapine fumarate in patients with major depressive disorder according to ongoing SSRI or SNRI treatment SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE adjunct therapy; antidepressant; augmentation; extended-release quetiapine fumarate; major depressive disorder; second-generation antipsychotic; serotonin-norepinephrine reuptake inhibitor; selective serotonin reuptake inhibitor ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; MAINTENANCE TREATMENT; XR MONOTHERAPY; TERM OUTCOMES; LONG-TERM; ANTIDEPRESSANT; AUGMENTATION; COMBINATION; TOLERABILITY AB This pooled analysis evaluated the efficacy of extended-release quetiapine fumarate (quetiapine XR) adjunct to selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) in patients with major depressive disorder (MDD). Pooled data were analyzed from two 6-week, double-blind, randomized, placebo-controlled trials of adjunct quetiapine XR (150 and 300 mg/day) in patients with MDD and inadequate response to initial antidepressant monotherapy. This post-hoc analysis included evaluation of change from randomization at week 6 in Montgomery angstrom sberg Depression Rating Scale (MADRS) total scores (primary endpoint), and week 6 MADRS response and remission rates for quetiapine XR as an adjunct to ongoing SSRI or SNRI. In total, 189, 178, and 202 patients received quetiapine XR 150 mg/day+SSRI, 300 mg/day+SSRI, and placebo+SSRI, respectively, whereas 82, 90, and 76 patients, respectively, received quetiapine XR 150 mg/day+SNRI, 300 mg/day+SNRI, and placebo+SNRI. At week 6, quetiapine XR 150 mg/day+SSRI and 300 mg/day+SSRI reduced the MADRS total score from randomization versus placebo+SSRI [least squares mean (LSM) change, -14.70 (P<0.05) -14.72 (P<0.05) vs. -12.59, respectively]. Quetiapine XR 150 mg/day+SNRI (LSM change, -14.68, P<0.01) and 300 mg/day+SNRI (LSM change, -14.99, P<0.01) also reduced the MADRS total score from randomization at week 6 versus placebo+SNRI (-10.77). In conclusion, in patients with MDD and inadequate response to ongoing antidepressant, adjunct quetiapine XR (150 and 300 mg/day) was effective in both SSRI and SNRI subgroups. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Bauer, Michael] Univ Hosp Carl Gustav Carus, Dept Psychiat & Psychotherapy, D-01307 Dresden, Germany. [Demyttenaere, Koen] Univ Hosp Gasthuisberg, Dept Psychiat, B-3000 Louvain, Belgium. [El-Khalili, Nizar] Alpine Clin, Lafayette, IL USA. [Thase, Michael E.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Papakostas, George I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Szamosi, Johan; Eriksson, Hans] AstraZeneca R&D, Sodertalje, Sweden. [Earley, Willie R.] AstraZeneca, Wilmington, DE USA. RP Bauer, M (reprint author), Univ Hosp Carl Gustav Carus, Dept Psychiat & Psychotherapy, D-01307 Dresden, Germany. EM michael.bauer@uniklinikum-dresden.de FU AstraZeneca Pharmaceuticals [D1448C00006, D1448C00007]; AstraZeneca FX These studies [D1448C00006 (Pearl) and D1448C00007 (Onyx)] were funded by AstraZeneca Pharmaceuticals. Both the studies were registered at ClinicalTrials.gov (D1448C00006 study identifier number NCT00326105; D1448C00007 study identifier number NCT00351910). The authors thank Jocelyn Woodcock, MPhil, from Complete Medical Communications, who provided medical writing support funded by AstraZeneca. The investigators involved in the two studies have been listed previously (Bauer et al., 2009; El-Khalili et al., 2010). NR 30 TC 3 Z9 3 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-1315 EI 1473-5857 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD JAN PY 2014 VL 29 IS 1 BP 16 EP 25 DI 10.1097/YIC.0000000000000011 PG 10 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 269FT UT WOS:000328227700002 PM 24108148 ER PT S AU Sahai, I Garganta, CL Bailey, J James, P Levy, HL Martin, M Neilan, E Phornphutkul, C Sweetser, DA Zytkovicz, TH Eaton, RB AF Sahai, I. Garganta, C. L. Bailey, J. James, P. Levy, H. L. Martin, M. Neilan, E. Phornphutkul, C. Sweetser, D. A. Zytkovicz, T. H. Eaton, R. B. BE Zschocke, J Gibson, KM Brown, G Morava, E Peters, V TI Newborn Screening for Glutaric Aciduria-II: The New England Experience SO JIMD REPORTS, VOL 13 SE JIMD Reports LA English DT Article; Book Chapter ID COA DEHYDROGENATION DEFICIENCY; ELECTRON-TRANSFER FLAVOPROTEIN; ACIDEMIA TYPE-II; UBIQUINONE OXIDOREDUCTASE; DISORDERS; MUTATIONS; ONSET AB Newborn screening (NBS) using tandem mass spectrometry (MS/MS) permits detection of neonates with Glutaric Aciduria-Type II (GA-II). We report follow-up of positive GA-II screens by the New England Newborn Screening Program. Methods: 1.5 million infants were screened for GA-II (Feb 1999-Dec 2012). Specialist consult was suggested for infants with two or more acylcarnitine elevations suggestive of GA-II. Results: 82 neonates screened positive for GA-II, 21 weighing > 1.5 kg and 61 weighing <= 1.5 kg. Seven (one weighing < 1.5 kg), were confirmed with GA-II. Four of these had the severe form (died < 1 week). The other three have a milder form and were identified because of newborn screening. Two (ages > 5 years) have a G-Tube in place, had multiple hospitalizations and are slightly hypotonic. The third infant remains asymptomatic (9 months old). Two GA-II carriers were also identified. The remaining positive screens were classified as false positives (FP). Six infants (> 1.5 kg) classified as FP had limited diagnostic work-up. Characteristics and outcomes of all specimens and neonates with a positive screen were reviewed, and marker profiles of the cases and FP were compared to identify characteristic profiles. Conclusion: In addition to the severe form of GA-II, milder forms of GA-II and some GA-II carriers are identified by newborn screening. Some positive screens classified as FP may be affected with a milder form of the disorder. Characteristic GA-II profiles, quantified as GA-II indexes, may be utilized to predict probability of disorder and direct urgency of intervention for positive screens. C1 [Sahai, I.; Bailey, J.; Zytkovicz, T. H.; Eaton, R. B.] Univ Massachusetts, Sch Med, New England Newborn Screening Program, Jamaica Plain, MA USA. [Sahai, I.; Martin, M.; Zytkovicz, T. H.; Eaton, R. B.] Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA USA. [Sahai, I.; Sweetser, D. A.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Sahai, I.; James, P.; Levy, H. L.; Neilan, E.; Sweetser, D. A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Garganta, C. L.] Tufts Med Ctr, Dept Pathol & Lab Med, Boston, MA USA. [James, P.; Levy, H. L.; Neilan, E.] Boston Childrens Hosp, Dept Med, Boston, MA USA. [Martin, M.] Univ Massachusetts, Med Ctr, Dept Pediat, Worcester, MA USA. [Phornphutkul, C.] Brown Univ, Rhode Isl Hosp, Dept Pediat, Providence, RI 02903 USA. RP Sahai, I (reprint author), 305 South St, Jamaica Plain, NY 02130 USA. EM inderneel.sahai@umassmed.edu NR 19 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 2192-8304 BN 978-3-642-54149-0; 978-3-642-54148-3 J9 JIMD REP PY 2014 VL 13 BP 1 EP 14 DI 10.1007/8904_2013_262 D2 10.1007/978-3-642-54149-0 PG 14 WC Endocrinology & Metabolism; Genetics & Heredity SC Endocrinology & Metabolism; Genetics & Heredity GA BE8SE UT WOS:000376976000001 PM 24190796 ER PT S AU Falk, MJ Li, D Gai, XW McCormick, E Place, E Lasorsa, FM Otieno, FG Hou, CP Kim, CE Abdel-Magid, N Vazquez, L Mentch, FD Chiavacci, R Liang, JL Liu, XZ Jiang, H Giannuzzi, G Marsh, ED Yiran, G Tian, LF Palmieri, F Hakonarson, H AF Falk, Marni J. Li, Dong Gai, Xiaowu McCormick, Elizabeth Place, Emily Lasorsa, Francesco M. Otieno, Frederick G. Hou, Cuiping Kim, Cecilia E. Abdel-Magid, Nada Vazquez, Lyam Mentch, Frank D. Chiavacci, Rosetta Liang, Jinlong Liu, Xuanzhu Jiang, Hui Giannuzzi, Giulia Marsh, Eric D. Yiran, Guo Tian, Lifeng Palmieri, Ferdinando Hakonarson, Hakon BE Zschocke, J Gibson, KM Brown, G Morava, E Peters, V TI AGC1 Deficiency Causes Infantile Epilepsy, Abnormal Myelination, and Reduced N-Acetylaspartate SO JIMD REPORTS, VOL 14 SE JIMD Reports LA English DT Article; Book Chapter ID TRANSPORTER FAMILY SLC25; MITOCHONDRIAL TRANSPORTER; CEREBRAL HYPOMYELINATION; DISEASE; CITRIN AB Background: Whole exome sequencing (WES) offers a powerful diagnostic tool to rapidly and efficiently sequence all coding genes in individuals presenting for consideration of phenotypically and genetically heterogeneous disorders such as suspected mitochondrial disease. Here, we report results of WES and functional validation in a consanguineous Indian kindred where two siblings presented with profound developmental delay, congenital hypotonia, refractory epilepsy, abnormal myelination, fluctuating basal ganglia changes, cerebral atrophy, and reduced N-acetylaspartate (NAA). Methods: Whole blood DNA from one affected and one unaffected sibling was captured by Agilent SureSelect Human All Exon kit and sequenced on the Illumina HiSeq2000. Mutations were validated by Sanger sequencing in all family members. Protein from wild-type and mutant fibroblasts was isolated to assess mutation effects on protein expression and enzyme activity. Results: A novel SLC25A12 homozygous missense mutation, c.1058G>A; p.Arg353Gln, segregated with disease in this kindred. SLC25A12 encodes the neuronal aspartate-glutamate carrier 1 (AGC1) protein, an essential component of the neuronal malate/aspartate shuttle that transfers NADH and H+ reducing equivalents from the cytosol to mitochondria. AGC1 activity enables neuronal export of aspartate, the glial substrate necessary for proper neuronal myelination. Recombinant mutant p.Arg353Gln AGC1 activity was reduced to 15% of wild type. One prior reported SLC25A12 mutation caused complete loss of AGC1 activity in a child with epilepsy, hypotonia, hypomyelination, and reduced brain NAA. Conclusions: These data strongly suggest that SLC25A12 disease impairs neuronal AGC1 activity. SLC25A12 sequencing should be considered in children with infantile epilepsy, congenital hypotonia, global delay, abnormal myelination, and reduced brain NAA. C1 [Falk, Marni J.; McCormick, Elizabeth; Place, Emily; Hakonarson, Hakon] Childrens Hosp Philadelphia, Div Human Genet, Dept Pediat, Philadelphia, PA 19104 USA. [Falk, Marni J.; McCormick, Elizabeth; Place, Emily] Childrens Hosp Philadelphia, Dept Pediat, Div Metab Dis, Philadelphia, PA 19104 USA. [Falk, Marni J.; McCormick, Elizabeth; Place, Emily; Marsh, Eric D.] Perelman Sch Med, Philadelphia, PA 19104 USA. [Li, Dong; Otieno, Frederick G.; Hou, Cuiping; Kim, Cecilia E.; Abdel-Magid, Nada; Vazquez, Lyam; Mentch, Frank D.; Chiavacci, Rosetta; Yiran, Guo; Tian, Lifeng; Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Abramson Res Ctr, Philadelphia, PA 19104 USA. [Gai, Xiaowu] Loyola Univ, Stritch Sch Med, Dept Mol Pharmacol & Therapeut, Maywood, IL 60153 USA. [Lasorsa, Francesco M.; Palmieri, Ferdinando] CNR, Inst Biomembranes & Bioenerget, I-70125 Bari, Italy. [Liang, Jinlong; Liu, Xuanzhu; Jiang, Hui] BGI Shenzhen, Shenzhen 518083, Peoples R China. [Giannuzzi, Giulia; Palmieri, Ferdinando] Univ Bari, Dept Biosci Biotechnol & Biopharmaceut, I-70125 Bari, Italy. [Marsh, Eric D.] Childrens Hosp Philadelphia, Div Pediat Neurol, Dept Pediat, Philadelphia, PA 19104 USA. [Marsh, Eric D.] Childrens Hosp Philadelphia, Div Pediat Neurol, Dept Neurol, Philadelphia, PA 19104 USA. [Hakonarson, Hakon] Childrens Hosp Philadelphia, Div Pulm Med, Philadelphia, PA 19104 USA. [Place, Emily] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Ocular Genom Inst, Boston, MA USA. RP Hakonarson, H (reprint author), Childrens Hosp Philadelphia, Div Pulm Med, Philadelphia, PA 19104 USA. EM falkm@email.chop.edu; Ferdinando.palmieri@uniba.it; Ferdinando.palmieri@uniba.it; hakonarson@email.chop.edu RI lasorsa, francesco massimo/B-7931-2008; Guo, Yiran/H-4120-2011 OI lasorsa, francesco massimo/0000-0001-8418-5222; Guo, Yiran/0000-0002-6549-8589 FU NCRR NIH HHS [UL1 RR024134]; NIDDK NIH HHS [R03 DK082521]; NINDS NIH HHS [K02 NS065975] NR 21 TC 10 Z9 10 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 2192-8304 BN 978-3-662-43748-3; 978-3-662-43747-6 J9 JIMD REP PY 2014 VL 14 BP 77 EP 85 DI 10.1007/8904_2013_287 D2 10.1007/978-3-662-43748-3 PG 9 WC Endocrinology & Metabolism; Genetics & Heredity SC Endocrinology & Metabolism; Genetics & Heredity GA BE8SF UT WOS:000376977100012 PM 24515575 ER PT S AU Falk, MJ Li, D Gai, XW McCormick, E Place, E Lasorsa, FM Otieno, FG Hou, CP Kim, CE Abdel-Magid, N Vazquez, L Mentch, FD Chiavacci, R Liang, JL Liu, XZ Jiang, H Giannuzzi, G Marsh, ED Guo, Y Tian, LF Palmieri, F Hakonarson, H AF Falk, Marni J. Li, Dong Gai, Xiaowu McCormick, Elizabeth Place, Emily Lasorsa, Francesco M. Otieno, Frederick G. Hou, Cuiping Kim, Cecilia E. Abdel-Magid, Nada Vazquez, Lyam Mentch, Frank D. Chiavacci, Rosetta Liang, Jinlong Liu, Xuanzhu Jiang, Hui Giannuzzi, Giulia Marsh, Eric D. Guo, Y. Tian, Lifeng Palmieri, Ferdinando Hakonarson, Hakon BE Zschocke, J Gibson, KM Brown, G Morava, E Peters, V TI AGC1 Deficiency Causes Infantile Epilepsy, Abnormal Myelination, and Reduced N-Acetylaspartate (vol 14, pg 77, 2014) SO JIMD REPORTS, VOL 14 SE JIMD Reports LA English DT Correction; Book Chapter C1 [Falk, Marni J.; McCormick, Elizabeth; Place, Emily; Hakonarson, Hakon] Childrens Hosp Philadelphia, Div Human Genet, Dept Pediat, Philadelphia, PA 19104 USA. [Falk, Marni J.; McCormick, Elizabeth; Place, Emily; Marsh, Eric D.; Hakonarson, Hakon] Perelman Sch Med, Philadelphia, PA 19104 USA. [Falk, Marni J.; McCormick, Elizabeth; Place, Emily] Childrens Hosp Philadelphia, Div Metab Dis, Dept Pediat, Philadelphia, PA 19104 USA. [Li, Dong; Otieno, Frederick G.; Hou, Cuiping; Kim, Cecilia E.; Abdel-Magid, Nada; Vazquez, Lyam; Mentch, Frank D.; Chiavacci, Rosetta; Guo, Y.; Tian, Lifeng; Hakonarson, Hakon] Childrens Hosp Philadelphia, Abramson Res Ctr, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Gai, Xiaowu] Loyola Univ, Stritch Sch Med, Dept Mol Pharmacol & Therapeut, Maywood, IL 60153 USA. [Lasorsa, Francesco M.; Palmieri, Ferdinando] CNR, Inst Biomembranes & Bioenerget, I-70125 Bari, Italy. [Liang, Jinlong; Liu, Xuanzhu; Jiang, Hui] BGI Shenzhen, Shenzhen 518083, Peoples R China. [Giannuzzi, Giulia; Palmieri, Ferdinando] Univ Bari, Dept Biosci Biotechnol & Biopharmaceut, I-70125 Bari, Italy. [Marsh, Eric D.] Childrens Hosp Philadelphia, Dept Pediat, Div Pediat Neurol, Philadelphia, PA 19104 USA. [Marsh, Eric D.] Childrens Hosp Philadelphia, Dept Neurol, Div Pediat Neurol, Philadelphia, PA 19104 USA. [Hakonarson, Hakon] Childrens Hosp Philadelphia, Div Pulm Med, Philadelphia, PA 19104 USA. [Place, Emily] Harvard Univ, Sch Med, Dept Ophthalmol, Ocular Genom Inst,Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Hakonarson, H (reprint author), Childrens Hosp Philadelphia, Div Pulm Med, Philadelphia, PA 19104 USA. EM falkm@email.chop.edu; Ferdinando.palmieri@uniba.it; hakonarson@email.chop.edu RI lasorsa, francesco massimo/B-7931-2008; Guo, Yiran/H-4120-2011 OI lasorsa, francesco massimo/0000-0001-8418-5222; Guo, Yiran/0000-0002-6549-8589 NR 1 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 2192-8304 BN 978-3-662-43748-3; 978-3-662-43747-6 J9 JIMD REP PY 2014 VL 14 BP 119 EP 119 DI 10.1007/8904_2014_314 D2 10.1007/978-3-662-43748-3 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity SC Endocrinology & Metabolism; Genetics & Heredity GA BE8SF UT WOS:000376977100016 PM 24973975 ER PT J AU Valderrabano, M Greenberg, S Razavi, H More, R Ryu, K Heist, EK AF Valderrabano, Miguel Greenberg, Steven Razavi, Hedi More, Rohan Ryu, Kyungmoo Heist, E. Kevin TI 3D Cardiovascular Navigation System: Accuracy and Reduction in Radiation Exposure in Left Ventricular Lead Implant SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE cardiac resynchronization therapy; electromagnetic navigation; LV lead; MediGuide; radiation exposure ID CARDIAC-RESYNCHRONIZATION THERAPY; HEART-FAILURE; INTERVENTIONAL CARDIOLOGISTS; ABLATION; TIME; TRACKING; INSIGHTS; REGISTRY; DEVICES; TRIAL AB Accurate 3D Navigation System for LV Lead Implant Introduction Cardiac resynchronization therapy implants entail significant radiation exposure for patients and physicians. A novel 3D electromagnetic cardiovascular navigation system (MediGuide (TM)) was designed to superimpose the real-time location of sensors embedded in delivery tools on prerecorded coronary sinus (CS) venograms while adjusting for patient movement and variations in heart rate under different C-arm angulations. We studied the accuracy and efficacy of MediGuide (TM) in reducing radiation exposure during LV lead implants. Methods and Results Fluoroscopy durations and radiation exposures were measured in 6 canines undergoing both conventional and MediGuide (TM)-guided LV lead implants. The in vivo accuracy of MediGuide (TM) was evaluated by obtaining CS venograms at 3 different C-arm angulations at 3 different heart rates and measuring the separation between the projected sensor icon of a MediGuide (TM) sensor-enabled guidewire and the encompassing branch on prerecorded venograms. Results Mediguide (TM)-guided implants resulted in significant reductions in fluoroscopy time (52 +/- 120 [median 6] vs 129 +/- 118 [median 90] sec, P < 0.001) and radiation exposure (13.8 +/- 32.4 [median 1.7] vs 49.2 +/- 45.3 [median 27.2] mu Gym(2), P = 0.03) compared to conventional implants. LV lead delivery time was not significantly different between the 2 implant techniques (P = 0.27). The mean separation between the projected guidewire sensor icon and its encompassing branch was 0.48 +/- 0.94 (median 0.00) mm. System accuracy was not affected by variations in heart rate or C-arm angulations. Conclusion The novel 3D cardiovascular navigation system enabled accurate and reliable tracking of sensor-enabled tools at varying heart rates and C-arm angulations with minimal need for fluoroscopy guidance, significantly reducing fluoroscopy time and radiation exposure. C1 [Valderrabano, Miguel] Methodist Hosp Syst, Houston, TX USA. [Greenberg, Steven] St Francis Hosp, Roslyn, NY USA. [Razavi, Hedi; More, Rohan; Ryu, Kyungmoo] St Jude Med, Sylmar, CA USA. [Heist, E. Kevin] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Valderrabano, M (reprint author), Cornell Univ, Weill Coll Med, 6560 Fannin St,Suite 1144, Houston, TX 77030 USA. EM MValderrabano@tmhs.org NR 31 TC 7 Z9 7 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-3873 EI 1540-8167 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD JAN PY 2014 VL 25 IS 1 BP 87 EP 93 DI 10.1111/jce.12290 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AF2BE UT WOS:000334516800004 ER PT J AU Ovretveit, J Hempel, S Magnabosco, JL Mittman, BS Rubenstein, LV Ganz, DA AF Ovretveit, John Hempel, Susanne Magnabosco, Jennifer L. Mittman, Brian S. Rubenstein, Lisa V. Ganz, David A. TI Guidance for research-practice partnerships (R-PPs) and collaborative research SO JOURNAL OF HEALTH ORGANIZATION AND MANAGEMENT LA English DT Article DE Knowledge sharing; Action research; Evidence-based practice; Research methods; Implementation; Research methodology AB Purpose - The purpose of this paper is to provide evidence based guidance to researchers and practice personnel about forming and carrying out effective research partnerships. Design/methodology/approach - A review of the literature, interviews and discussions with colleagues in both research and practice roles, and a review of the authors' personal experiences as researchers in partnership research. Findings - Partnership research is, in some respects, a distinct "approach" to research, but there are many different versions. An analysis of research publications and of their research experience led the authors to develop a framework for planning and assessing the partnership research process, which includes defining expected outcomes for the partners, their roles, and steps in the research process. Practical implications - This review and analysis provides guidance that may reduce commonly-reported misunderstandings and help to plan more successful partnerships and projects. It also identifies future research which is needed to define more precisely the questions and purposes for which partnership research is most appropriate, and methods and designs for specific types of partnership research. Originality/value - As more research moves towards increased participation of practitioners and patients in the research process, more precise and differentiated understanding of the different partnership approaches is required, and when each is most suitable. This article describes research approaches that have the potential to reduce "the research-practice gap". It gives evidence- and experience-based guidance for choosing and establishing a partnership research process, so as to improve partnership relationship-building and more actionable research. C1 [Ovretveit, John] Karolinska Inst, MMC, Stockholm, Sweden. [Hempel, Susanne; Rubenstein, Lisa V.; Ganz, David A.] RAND Corp, Santa Monica, CA USA. [Magnabosco, Jennifer L.] VA QUERI Calif Mental Hlth Serv Author, Los Angeles, CA USA. [Magnabosco, Jennifer L.] Yo San Univ Tradit Chinese Med, Los Angeles, CA USA. [Mittman, Brian S.; Rubenstein, Lisa V.; Ganz, David A.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Mittman, Brian S.; Rubenstein, Lisa V.] VA QUERI Ctr Implementat Practice & Res Support, Sepulveda, CA USA. [Mittman, Brian S.] Kaiser Permanente Southern Calif Dept Res & Evalu, Oakland, CA USA. [Rubenstein, Lisa V.; Ganz, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Ovretveit, J (reprint author), Karolinska Inst, MMC, Stockholm, Sweden. EM jovret@aol.com FU US Department of Veterans Affairs, Veterans Health Administration Quality Enhancement Research Initiative [TRA 08-379]; US Department of Veterans Affairs, Health Services Research and Development (HSRD) Service [VA CD2 08-012-1] FX This project was funded by the US Department of Veterans Affairs, Veterans Health Administration Quality Enhancement Research Initiative through core funding to the Center for Implementation Practice and Research Support (Project # TRA 08-379). Additional support for investigator time and visiting professorship was provided from the Medical Management Center, Karolinska Institutet, Stockholm, and by a Career Development Award to David Ganz from the US Department of Veterans Affairs, Health Services Research and Development (HSR&D) Service (Project #VA CD2 08-012-1). NR 34 TC 8 Z9 8 U1 0 U2 0 PU EMERALD GROUP PUBLISHING LTD PI BINGLEY PA HOWARD HOUSE, WAGON LANE, BINGLEY BD16 1WA, W YORKSHIRE, ENGLAND SN 1477-7266 EI 1758-7247 J9 J HEALTH ORGAN MANAG JI J. Health Organ. Manag. PY 2014 VL 28 IS 1 BP 115 EP 126 DI 10.1108/JHOM-08-2013-0164 PG 12 WC Health Policy & Services SC Health Care Sciences & Services GA V46NN UT WOS:000209891000007 PM 24783669 ER PT J AU Wang, MP Wang, X Viswanath, K Wan, A Lam, TH Chan, SS AF Wang, Man Ping Wang, Xin Viswanath, Kasisomayajula Wan, Alice Tai Hing Lam Chan, Sophia S. TI Digital Inequalities of Family Life Information Seeking and Family Well-Being Among Chinese Adults in Hong Kong: A Population Survey SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE socioeconomic factors; information seeking behavior; family health AB Background: Inequalities in Internet use and health information seeking are well documented, but less is known about information for family life activities. Objective: We investigated the social determinants of online family life information seeking behaviors and its associations with family well-being among Chinese adults in Hong Kong. Methods: A probability-based telephone survey was conducted in 2012 to record family life information seeking behaviors, including frequency of seeking and paying attention to family life information, levels of trust, and perceived usefulness of family life information. Family well-being was assessed using 3 single items on perceived family harmony, happiness, and health, with higher scores indicating greater well-being. Adjusted odds ratios for family life information seeking behaviors by socioeconomic characteristics and lifestyle behaviors, and adjusted beta coefficients for family well-being by family life information seeking behaviors were calculated. Results: Of 1537 respondents, 57.57% (855/1537) had ever and 26.45% (407/1537) sought monthly family life information through the Internet. Lower educational attainment and household income, smoking, and physical inactivity were associated with less frequent seeking and paying attention (all P<.05). Greater perceived family health was associated with more frequent attention (adjusted beta=.32, 95% CI.11-.52), greater levels of trust (adjusted beta=.28, 95% CI.07-.48), and perceived usefulness (adjusted beta=.23, 95% CI.01-.45) of family life information. Frequent attention and higher level of trust were also associated with greater family harmony (adjusted beta=.22, 95% CI.002-.41) and happiness (adjusted beta=.23, 95% CI.003-. 42), respectively. Conclusions: This is the first study investigating family life information seeking behaviors and suggested inequalities of online family life information seeking behaviors. The association between family life information seeking behavior and family well-being needs to be confirmed in prospective studies. C1 [Wang, Man Ping; Chan, Sophia S.] Univ Hong Kong, Sch Nursing, Hong Kong, Hong Kong, Peoples R China. [Wang, Xin; Wan, Alice; Tai Hing Lam] Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China. [Viswanath, Kasisomayajula] Harvard Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA USA. [Viswanath, Kasisomayajula] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP Lam, TH (reprint author), Univ Hong Kong, Sch Publ Hlth, 5-F WMMW Block 23 Sassoon Rd, Pokfulam, Hong Kong, Peoples R China. EM hrmrlth@hku.hk FU Hong Kong Jockey Club Charities Trust FX The project was funded by the Hong Kong Jockey Club Charities Trust. We would like to thank the participants who participated in the telephone surveys and Public Opinion Programme (HKU) for conducting the surveys. NR 36 TC 3 Z9 3 U1 2 U2 9 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PY 2014 VL 16 IS 10 BP 275 EP 285 AR e227 DI 10.2196/jmir.3386 PG 11 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA V46LH UT WOS:000209885200022 PM 25281831 ER PT J AU Cope, L Naiman, DQ Parmigiani, G AF Cope, Leslie Naiman, Daniel Q. Parmigiani, Giovanni TI Integrative correlation: Properties and relation to canonical correlations SO JOURNAL OF MULTIVARIATE ANALYSIS LA English DT Article DE Statistics; Bioinformatics; Gene expression; Correlation; Cross-study validation; Reproducibility ID DIFFERENTIALLY EXPRESSED GENES; MICROARRAY EXPERIMENTS; METAANALYSIS METHODS; DRUG DISCOVERY; BREAST-CANCER; LUNG-CANCER; CHEMOSENSITIVITY; PREDICTORS; SUBTYPES AB The integrative correlation coefficient was developed to facilitate the validation of expression microarray results in public datasets, by identifying genes that are reproducibly measured across studies and even across microarray platforms. In the current study, we develop a number of interesting and important mathematical and statistical properties of the integrative correlation coefficient, including a unique permutation-based null distribution with the unusual property that the variance does not shrink as the sample size increases, discussing how these findings impact its use and interpretation, and what they have to say about any method for identifying reproducible genes in a meta-analysis. (C) 2013 Elsevier Inc. All rights reserved. C1 [Cope, Leslie] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21218 USA. [Naiman, Daniel Q.] Johns Hopkins Univ, Whiting Sch Engn, Dept Appl Math & Stat, Baltimore, MD 21218 USA. [Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA USA. [Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. RP Cope, L (reprint author), Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21218 USA. EM cope@jhu.edu; daniel.naiman@jhu.edu; gp@jimmy.harvard.edu FU NSF [NSF034211] FX Work supported by NSF Grant: NSF034211. NR 30 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0047-259X J9 J MULTIVARIATE ANAL JI J. Multivar. Anal. PD JAN PY 2014 VL 123 BP 270 EP 280 DI 10.1016/j.jmva.2013.09.011 PG 11 WC Statistics & Probability SC Mathematics GA 264VD UT WOS:000327908200018 PM 26028790 ER PT J AU Galon, J Mlecnik, B Bindea, G Angell, HK Berger, A Lagorce, C Lugli, A Zlobec, I Hartmann, A Bifulco, C Nagtegaal, ID Palmqvist, R Masucci, GV Botti, G Tatangelo, F Delrio, P Maio, M Laghi, L Grizzi, F Asslaber, M D'Arrigo, C Vidal-Vanaclocha, F Zavadova, E Chouchane, L Ohashi, PS Hafezi-Bakhtiari, S Wouters, BG Roehrl, M Nguyen, L Kawakami, Y Hazama, S Okuno, K Ogino, S Gibbs, P Waring, P Sato, N Torigoe, T Itoh, K Patel, PS Shukla, SN Wang, YL Kopetz, S Sinicrope, FA Scripcariu, V Ascierto, PA Marincola, FM Fox, BA Pages, F AF Galon, Jerome Mlecnik, Bernhard Bindea, Gabriela Angell, Helen K. Berger, Anne Lagorce, Christine Lugli, Alessandro Zlobec, Inti Hartmann, Arndt Bifulco, Carlo Nagtegaal, Iris D. Palmqvist, Richard Masucci, Giuseppe V. Botti, Gerardo Tatangelo, Fabiana Delrio, Paolo Maio, Michele Laghi, Luigi Grizzi, Fabio Asslaber, Martin D'Arrigo, Corrado Vidal-Vanaclocha, Fernando Zavadova, Eva Chouchane, Lotfi Ohashi, Pamela S. Hafezi-Bakhtiari, Sara Wouters, Bradly G. Roehrl, Michael Nguyen, Linh Kawakami, Yutaka Hazama, Shoichi Okuno, Kiyotaka Ogino, Shuji Gibbs, Peter Waring, Paul Sato, Noriyuki Torigoe, Toshihiko Itoh, Kyogo Patel, Prabhu S. Shukla, Shilin N. Wang, Yili Kopetz, Scott Sinicrope, Frank A. Scripcariu, Viorel Ascierto, Paolo A. Marincola, Francesco M. Fox, Bernard A. Pages, Franck TI Towards the introduction of the 'Immunoscore' in the classification of malignant tumours SO JOURNAL OF PATHOLOGY LA English DT Review DE Immunoscore; colorectal cancer; colon carcinoma; tumour microenvironment; immune response; classification; prognostic markers; predictive markers; T cells ID ISLAND METHYLATOR PHENOTYPE; POPULATION-BASED SAMPLE; T-CELL SUBSETS; COLORECTAL-CANCER; MICROSATELLITE INSTABILITY; COLON-CANCER; INFILTRATING LYMPHOCYTES; IMMUNE CELLS; PROGNOSTIC-FACTOR; CLINICAL IMPACT AB The American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) TNM staging system provides the most reliable guidelines for the routine prognostication and treatment of colorectal carcinoma. This traditional tumour staging summarizes data on tumour burden (T), the presence of cancer cells in draining and regional lymph nodes (N) and evidence for distant metastases (M). However, it is now recognized that the clinical outcome can vary significantly among patients within the same stage. The current classification provides limited prognostic information and does not predict response to therapy. Multiple ways to classify cancer and to distinguish different subtypes of colorectal cancer have been proposed, including morphology, cell origin, molecular pathways, mutation status and gene expression-based stratification. These parameters rely on tumour-cell characteristics. Extensive literature has investigated the host immune response against cancer and demonstrated the prognostic impact of the in situ immune cell infiltrate in tumours. A methodology named Immunoscore' has been defined to quantify the in situ immune infiltrate. In colorectal cancer, the Immunoscore may add to the significance of the current AJCC/UICC TNM classification, since it has been demonstrated to be a prognostic factor superior to the AJCC/UICC TNM classification. An international consortium has been initiated to validate and promote the Immunoscore in routine clinical settings. The results of this international consortium may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune). (c) 2013 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. C1 [Galon, Jerome; Mlecnik, Bernhard; Bindea, Gabriela; Angell, Helen K.; Pages, Franck] INSERM, Lab Integrat Canc Immunol, U872, F-75006 Paris, France. [Galon, Jerome; Mlecnik, Bernhard; Bindea, Gabriela; Angell, Helen K.; Pages, Franck] Univ Paris 05, Paris, France. [Galon, Jerome; Mlecnik, Bernhard; Bindea, Gabriela; Angell, Helen K.; Pages, Franck] Univ Paris 06, Ctr Rech Cordeliers, F-75252 Paris 05, France. [Berger, Anne] Georges Pompidou European Hosp, Dept Digest Surg, Paris, France. [Lagorce, Christine] Avicenne Hosp, Dept Pathol, Bobigny, France. [Lugli, Alessandro; Zlobec, Inti] Univ Bern, Inst Pathol, CH-3012 Bern, Switzerland. [Hartmann, Arndt] Univ Erlangen Nurnberg, Dept Pathol, Erlangen, Germany. [Bifulco, Carlo] Providence Portland Med Ctr, Dept Pathol, Portland, OR USA. [Nagtegaal, Iris D.] Radboud Univ Nijmegen, Med Ctr, Dept Pathol, NL-6525 ED Nijmegen, Netherlands. [Palmqvist, Richard] Umea Univ, Dept Med Biosci, S-90187 Umea, Sweden. [Masucci, Giuseppe V.] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden. [Botti, Gerardo; Tatangelo, Fabiana] Fdn G Pascale, Ist Nazl Studio & Cura Tumouri, Dept Pathol, Naples, Italy. [Delrio, Paolo] Fdn G Pascale, Ist Nazl Studio & Cura Tumouri, Dept Colorectal Surg, Naples, Italy. [Maio, Michele] Univ Hosp Siena, Ist Toscano Tumouri, Div Med Oncol & Immunotherapy, Siena, Italy. [Laghi, Luigi; Grizzi, Fabio] Humanitas Clin & Res Ctr, Milan, Italy. [Laghi, Luigi; Grizzi, Fabio] Humanitas Clin & Res Ctr, Dept Gastroenterol, Milan, Italy. [Asslaber, Martin] Med Univ Graz, Inst Pathol, Graz, Austria. [D'Arrigo, Corrado] Dorset Cty Hosp, Dept Histopathol, Dorchester, England. [Vidal-Vanaclocha, Fernando] CEU San Pablo Univ, Sch Med, Madrid, Spain. [Vidal-Vanaclocha, Fernando] HM Hosp, Madrid Sci Fdn, Inst Appl Mol Med IMMA, Madrid, Spain. [Zavadova, Eva] Charles Univ Prague, Dept Oncol, Fac Med 1, Prague, Czech Republic. [Zavadova, Eva] Gen Hosp, Prague, Czech Republic. [Chouchane, Lotfi] Weill Cornell Med Coll, Doha, Qatar. [Ohashi, Pamela S.] Princess Margaret Hosp, Ontario Canc Inst, Univ Hlth Network, Toronto, ON M4X 1K9, Canada. [Ohashi, Pamela S.] Princess Margaret Hosp, Campbell Family Inst Canc Res, Univ Hlth Network, Toronto, ON M4X 1K9, Canada. [Hafezi-Bakhtiari, Sara; Wouters, Bradly G.] Univ Hlth Network, Dept Pathol & Lab Med, Toronto, ON, Canada. [Roehrl, Michael] Univ Hlth Network, UHN Program BioSpecimen Sci, Toronto, ON, Canada. [Nguyen, Linh] Univ Hlth Network, Princess Margaret Canc Ctr, Campbell Family Inst Breast Canc Res, Toronto, ON, Canada. [Kawakami, Yutaka] Keio Univ, Sch Med, Inst Adv Med Res, Div Cellular Signalling, Tokyo, Japan. [Hazama, Shoichi] Yamaguchi Univ, Grad Sch Med, Dept Digest Surg & Surg Oncol, Yamaguchi, Japan. [Okuno, Kiyotaka] Kinki Univ, Sch Med, Dept Surg, Osaka 589, Japan. [Ogino, Shuji] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Gibbs, Peter] Royal Melbourne Hosp, Dept Med Oncol, Melbourne, Vic, Australia. [Waring, Paul] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. [Sato, Noriyuki] Sapporo Med Univ, Sch Med, Dept Pathol, Sapporo, Hokkaido, Japan. [Itoh, Kyogo] Kurume Univ, Sch Med, Dept Immunol & Immunotherapy, Kurume, Fukuoka, Japan. [Patel, Prabhu S.; Shukla, Shilin N.] Gujarat Canc Res Inst, Ahmadabad, Gujarat, India. [Wang, Yili] Xi An Jiao Tong Univ, Ctr Translat Med, Inst Canc Res, Xian 710049, Peoples R China. [Kopetz, Scott] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Sinicrope, Frank A.] Mayo Clin, Rochester, MN 55905 USA. [Sinicrope, Frank A.] Mayo Coll Med, Rochester, MN 55905 USA. [Scripcariu, Viorel] Univ Med & Pharm Gr T Popa, Dept Surg Oncol, Reg Inst Oncol, Dept Surg, Iasi, Romania. [Ascierto, Paolo A.] Fdn G Pascale, Ist Nazl Studio & Cura Tumouri, Med Oncol & Innovat Therapies Unit, Naples, Italy. [Marincola, Francesco M.] Sidra Med & Res Ctr, Res Branch, Doha, Qatar. [Fox, Bernard A.] Providence Portland Med Ctr, Robert W Franz Canc Ctr, Earle A Chiles Res Inst, Lab Mol & Tumour Immunol, Portland, OR USA. [Fox, Bernard A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. [Pages, Franck] Georges Pompidou European Hosp, Immunol Lab, Paris, France. RP Galon, J (reprint author), INSERM, Lab Integrat Canc Immunol, Cordeliers Res Ctr, U872, 15 Rue Ecole Med, F-75006 Paris, France. EM jerome.galon@crc.jussieu.fr RI Nagtegaal, Iris/A-2448-2014; Kawakami, Yutaka /E-7429-2013; OI Nagtegaal, Iris/0000-0003-0887-4127; Kawakami, Yutaka /0000-0003-4836-2855; Gibbs, Peter/0000-0003-1423-4484; Masucci, Giuseppe/0000-0002-9583-2306; coral, sandra/0000-0002-1308-3082 FU Institut National du Cancer, France (INCa); Assistance Publique-Hopitaux de Paris; national PHRC programme IMMUCOL; Canceropole Ile de France; INSERM; MedImmune; Qatar National Research Fund under its National Priorities Research Programme [NPRP09-1174-3-291]; European Commission [202230]; Cancer Research for Personalized Medicine (CARPEM); LabEx Immuno-oncology FX We acknowledge all the scientists who made contributions to the area of research reviewed here that were not cited due to space constraints. The work performed in the Laboratory of Integrative Cancer Immunology and the immunomonitoring platform of the HEGP hospital was supported by grants from the Institut National du Cancer, France (INCa), Assistance Publique-Hopitaux de Paris, the national PHRC programme IMMUCOL, the Canceropole Ile de France, INSERM, MedImmune, Qatar National Research Fund under its National Priorities Research Programme (Award No. NPRP09-1174-3-291), the European Commission (7FP, Geninca Consortium; Grant No. 202230), Cancer Research for Personalized Medicine (CARPEM) and the LabEx Immuno-oncology. The authors wish to acknowledge the following organizations for supporting the Immunoscore following the WIC meeting: Society for Immunotherapy of Cancer (SITC); the European Academy of Tumour Immunology (EATI); La Fondazione Melanoma Onlus; National Cancer Institute, USA (NCI); Biotherapy Development Association (BDA); Canadian Cancer Immunotherapy Consortium (CCIC); Cancer Immunotherapy Consortium (CIC); Cancer Research Institute (CRI); Association for Cancer Immunotherapy (CIMT); Committee for Tumour Immunology and Biotherapy (TIBT); European Society for Cancer Immunology and Immunotherapy (ESCII); Italian Network for Tumour Biotherapy (NIBIT); Japanese Association of Cancer Immunology (JACI); Nordic Centre for Development of Antitumour Vaccines (NCV-Network); Progress in Vaccination Against Cancer (PIVAC); Adoptive engineered T cell Targeting to Activate Cancer Killing (ATTACK); Tumour Vaccine and Cell Therapy Working Group (TVACT); and Institut National du Cancer, France (INCa). NR 70 TC 206 Z9 208 U1 19 U2 72 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3417 EI 1096-9896 J9 J PATHOL JI J. Pathol. PD JAN PY 2014 VL 232 IS 2 BP 199 EP 209 DI 10.1002/path.4287 PG 11 WC Oncology; Pathology SC Oncology; Pathology GA 269DI UT WOS:000328220600012 PM 24122236 ER PT J AU Wang, H Shun, MC Li, X Di Nunzio, F Hare, S Cherepanov, P Engelman, A AF Wang, Hao Shun, Ming-Chieh Li, Xiang Di Nunzio, Francesca Hare, Stephen Cherepanov, Peter Engelman, Alan TI Efficient transduction of LEDGF/p75 mutant cells by complementary gain-of-function HIV-1 integrase mutant viruses SO MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT LA English DT Article AB Controlling the specificity of retroviral DNA integration could improve the safety of gene therapy vectors, and fusions of heterologous chromatin binding modules to the integrase (IN)-binding domain from the lentiviral integration host cofactor lens epithelium-derived growth factor (LEDGF)/p75 are a promising retargeting strategy. We previously proposed the utility of IN mutant lentiviral vectors that are selectively activated by complementary LEDGF/p75 variants, and our initial modifications in human immunodeficiency virus type 1 IN and LEDGF/p75 supported about 13% of wild-type vector transduction activity. Here we describe the selection and characterization of the K42E gain-of-function mutation in IN, which greatly improves the efficiency of this system. Both K42E and initial reverse-charge mutations in IN negatively affected reverse transcription and integration, yet when combined together boosted viral transduction efficiency to similar to 75% of the wild-type vector in a manner dependent on a complementary LEDGF/p75 variant. Although the K42E mutation conferred functional gains to IN mutant viral reverse transcription and integration, only the integration boost depended on the engineered LEDGF/p75 mutant. We conclude that the specificity of lentiviral retargeting strategies based on heterologous LEDGF/p75 fusion proteins will benefit from our optimized system that utilizes the unique complementation properties of reverse-charge IN mutant viral and LEDGF/p75 host proteins. C1 [Wang, Hao; Shun, Ming-Chieh; Li, Xiang; Di Nunzio, Francesca; Engelman, Alan] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Wang, Hao; Shun, Ming-Chieh; Li, Xiang; Di Nunzio, Francesca; Engelman, Alan] Harvard Med Sch, Dept Med, Boston, MA USA. [Hare, Stephen; Cherepanov, Peter] Imperial Coll London, Div Infect Dis, London, England. [Cherepanov, Peter] Canc Res UK, London Res Inst, Clare Hall Labs, Potters Bar, Herts, England. RP Engelman, A (reprint author), Harvard Med Sch, Dept Med, Boston, MA USA. EM alan_engelman@dfci.harvard.edu FU US National Institutes of Health [AI039394, AI060354] FX We thank Eric Poeschla (Mayo Clinic, Rochester, MN) for the generous contribution of TL3 cells. This work was supported by grants AI039394 (to A.E.) and AI060354 (to the Harvard University Center for AIDS Research) from the US National Institutes of Health. NR 50 TC 1 Z9 2 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2329-0501 J9 MOL THER-METH CLIN D JI Mol.Ther.-Methods Clin. Dev. PY 2014 VL 1 AR UNSP 2 DI 10.1038/mtm.2013.2 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA V46YD UT WOS:000209918600002 ER PT J AU Lo, ASY Xu, C Murakami, A Marasco, WA AF Lo, Agnes Shuk-Yee Xu, Chen Murakami, Akikazu Marasco, Wayne A. TI Regression of established renal cell carcinoma in nude mice using lentivirus-transduced human T cells expressing a human anti-CAIX chimeric antigen receptor SO MOLECULAR THERAPY-ONCOLYTICS LA English DT Article AB Carbonic anhydrase IX (CAIX) is a tumor-associated antigen and marker of hypoxia that is overexpressed on > 90% of clear-cell type renal cell carcinoma (RCC) but not on neighboring normal kidney tissue. Here, we report on the construction of two chimeric antigen receptors (CARs) that utilize a carbonic anhydrase (CA) domain mapped, human single chain antibody (scFv G36) as a targeting moiety but differ in their capacity to provide costimulatory signaling for optimal T cell proliferation and tumor cell killing. The resulting antiCAIX CARs were expressed on human primary T cells via lentivirus transduction. CAR-transduced T cells (CART cells) expressing secondgeneration G36-CD28-TCR zeta exhibited more potent in vitro antitumor effects on CAIX(+)RCC cells than first--generation G36-CD8-TCR. including cytotoxicity, cytokine secretion, proliferation, and clonal expansion. Adoptive G36-CD28-TCR zeta CART cell therapy combined with high-dose interleukin (IL)-2 injection also lead to superior regression of established RCC in nude mice with evidence of tumor cell apoptosis and tissue necrosis. These results suggest that the fully human G36-CD28-TCR zeta. CARs should provide substantial improvements over first-generation mouse anti-CAIX CARs in clinical use through reduced human anti-mouse antibody responses against the targeting scFv and administration of lower doses of T cells during CART cell therapy of CAIX(+)RCC. C1 [Lo, Agnes Shuk-Yee; Xu, Chen; Murakami, Akikazu; Marasco, Wayne A.] Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA. [Lo, Agnes Shuk-Yee; Xu, Chen; Murakami, Akikazu; Marasco, Wayne A.] Dana Farber Canc Inst, AIDS, Boston, MA 02115 USA. [Lo, Agnes Shuk-Yee; Xu, Chen; Murakami, Akikazu; Marasco, Wayne A.] Harvard Med Sch, Dept Med, Boston, MA USA. [Lo, Agnes Shuk-Yee] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Xu, Chen] Beijing Triprime Genet Engn Co Ltd, Beijing, Peoples R China. [Murakami, Akikazu] Univ Ryukyus, Grad Sch Med, Dept Parasitol & Immunopathoetiol, Okinawa, Japan. RP Marasco, WA (reprint author), Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA. EM wayne_marasco@dfci.harvard.edu FU NIH [R21DK072282] FX We thank Zeng Qing for technical assistance, XiaoYin Xu for assisting with the animal studies, Aimee Tallarico for assisting with DNA analysis of vectors used in this paper and for help with the final draft of the manuscript. We also thank De-Kuan Chang for immunohistochemical analysis of the tissue samples and Quan Karen Zhu for her overall support in the project. We are also grateful to David Cook for reviewing the manuscript. We thank Gerd Ritter, Department of Human Cancer Immunology, Ludwig Institute for Cancer Research for providing the RCC cell lines (sk-rc-52, sk-rc-44 and sk-rc-59), Richard Mulligan, Harvard Gene Therapy Initiative, Harvard Medical School for providing the pHAGE lentiviral vector, and Andrew Kung, Department of Pediatric Oncology, Dana-Farber Cancer Institute, for offering the retroviral supernatant expressing firefly luciferase. We thank Aimee St. Clair Tallarico for her assistance in graphic design. A.S.-Y.L. and W.A.M. designed research and wrote the paper; C.X. provided anti-CAIX scFvs; A.M. provided CAIX cDNA. This work was supported by NIH grant R21DK072282 to W.A.M. NR 50 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2372-7705 J9 Mol Ther-Oncolytics JI Mol. Ther.-Oncolytics PY 2014 VL 1 AR UNSP 14003 DI 10.1038/mto.2014.3 PG 12 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA V45LF UT WOS:000209817400003 PM 27119093 ER PT B AU Humphrey, PA Young, RH AF Humphrey, Peter A. Young, Robert H. BA Humphrey, PA Manivel, JC Young, RH BF Humphrey, PA Manivel, JC Young, RH TI Pseudoneoplastic Lesions of the Urinary Tract SO NEOPLASTIC MIMICS IN GENITOURINARY PATHOLOGY SE Pathology of Neoplastic Mimics Series LA English DT Article; Book Chapter C1 [Humphrey, Peter A.] Washington Univ, Sch Med, Barnes Jewish Hosp, Pathol & Immunol, St Louis, MO USA. [Humphrey, Peter A.] Washington Univ, Sch Med, Barnes Jewish Hosp, Div Anat & Mol Pathol, St Louis, MO USA. [Young, Robert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pathol, Boston, MA USA. [Young, Robert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gynecol & Urol Pathol, Boston, MA USA. RP Humphrey, PA (reprint author), Washington Univ, Sch Med, Barnes Jewish Hosp, Pathol & Immunol, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-020-4 J9 PATHOL NEOPLAST MIM PY 2014 BP 33 EP 92 PG 60 WC Pathology; Urology & Nephrology SC Pathology; Urology & Nephrology GA BE3YK UT WOS:000371361400003 ER PT B AU Humphrey, PA Young, RH AF Humphrey, Peter A. Young, Robert H. BA Humphrey, PA Manivel, JC Young, RH BF Humphrey, PA Manivel, JC Young, RH TI Pseudoneoplastic Lesions of the Prostate SO NEOPLASTIC MIMICS IN GENITOURINARY PATHOLOGY SE Pathology of Neoplastic Mimics Series LA English DT Article; Book Chapter C1 [Humphrey, Peter A.] Washington Univ, Sch Med, Barnes Jewish Hosp, Pathol & Immunol, St Louis, MO USA. [Humphrey, Peter A.] Washington Univ, Sch Med, Barnes Jewish Hosp, Div Anat & Mol Pathol, St Louis, MO USA. [Young, Robert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pathol, Boston, MA USA. [Young, Robert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gynecol & Urol Pathol, Boston, MA USA. RP Humphrey, PA (reprint author), Washington Univ, Sch Med, Barnes Jewish Hosp, Pathol & Immunol, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-020-4 J9 PATHOL NEOPLAST MIM PY 2014 BP 93 EP 155 PG 63 WC Pathology; Urology & Nephrology SC Pathology; Urology & Nephrology GA BE3YK UT WOS:000371361400004 ER PT S AU Gray, NS Fabbro, D AF Gray, Nathanael S. Fabbro, Doriano BE Shokat, KM TI Discovery of Allosteric Bcr-Abl Inhibitors from Phenotypic Screen to Clinical Candidate SO PROTEIN KINASE INHIBITORS IN RESEARCH AND MEDICINE SE Methods in Enzymology LA English DT Review; Book Chapter ID CHRONIC MYELOID-LEUKEMIA; BINDING-SITE; C-ABL; TYROSINE KINASE; IN-VITRO; IMATINIB; SKI-606; POTENT; CELLS; BMS-354825 AB The development of imatinib, an ATP-competitive inhibitor of the BCR-ABL oncoprotein, has revolutionized the treatment of chronic myelogenous leukemia (CML). Unfortunately, the leukemia eventually becomes resistant imatinib as a result of emergence of cells expressing drug insensitive BCR-ABL mutant proteins. This has motivated the development of several next-generation ATP-competitive drugs. This chapter describes the discovery and development of a complementary strategy involving inhibiting BCR-ABL by targeting an allosteric binding site. Compounds that bind to the myristate-binding pocket of BCR-ABL are able to induce formation of an "inactive" state and are able to overcome resistance mutations located in the ATP-binding pocket including the recalcitrant T315I "gatekeeper" mutation. Myristate-pocket inhibitors are also able to function synergistically with ATP-competitive inhibitors in cellular and murine models of CML and this dual inhibitory strategy is currently being investigated in the clinic. C1 [Gray, Nathanael S.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Fabbro, Doriano] PIQUR Therapeut AG, Basel, Switzerland. RP Gray, NS (reprint author), Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. EM nsgray01@gmail.com NR 30 TC 5 Z9 5 U1 2 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-397918-6 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2014 VL 548 BP 173 EP 188 DI 10.1016/B978-0-12-397918-6.00007-0 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BF4XO UT WOS:000381759100008 PM 25399646 ER PT J AU Vukovic, IS Jovanovic, N Kolaric, B Vidovic, V Mollica, RF AF Vukovic, Iris Sarajlic Jovanovic, Nikolina Kolaric, Branko Vidovic, Vesna Mollica, Richard Francis TI PSYCHOLOGICAL AND SOMATIC HEALTH PROBLEMS IN BOSNIAN REFUGEES: A THREE YEAR FOLLOW-UP SO PSYCHIATRIA DANUBINA LA English DT Article DE posttraumatic stress disorders; depression; medical illnesses; refugee; longitudinal study AB Background: Aim of this study was to explore association between psychiatric disorders (PTSD and depression) and chronic medical illnesses in a group of Bosnian refugees followed up for three years (1996-1999). Subjects and methods: Study was conducted in refugee camps in Varazdin, Nbaseline=534, Nendpoint=376 (70.4%). The interviews were conducted in Bosnian, data on depression and PTSD were collected using the Hopkins Symptom Checklist-25 and Harvard Trauma Questionnaire, respectively. Medical conditions were self-reported. Results: Most important findings: 1) Half of the sample at both study points reported no psychiatric problems (N=294, 55% vs. N=225, 59%), others suffered from depression (N=99, 18.5% at both times), PTSD (N=30, 5.6% vs. N=15, 4%), and depression + PTSD (N=129, 24.2% vs. N=114, 30.3%); 2) A total of 15 medical conditions were identified, and most frequently present were high blood pressure (N=201, 37.6%) and heart disease (N=167, 31.3%); 3) Occurrence of medical conditions was related to the clinical group - they were more frequent in subjects diagnosed with depression and depression + PTSD, than in those who were asymptomatic or suffering from PTSD only. Conclusions: Our data indicate the persistence of both psychological and somatic health problems in Bosnian refugees involved in this study over time. Holistic approach and avoiding of mind-body dualism might be beneficial for the care and long-term prognosis of these people. C1 [Vukovic, Iris Sarajlic] Andrija Stampar Teaching Inst Publ Hlth, Dept Mental Hlth & Addict Prevent, Mirogojska Cesta 16, HR-10000 Zagreb, Croatia. [Jovanovic, Nikolina] Clin Hosp Ctr Zagreb, Dept Psychiat, Zagreb, Croatia. [Jovanovic, Nikolina] Univ Zagreb, Sch Med, Dept Psychiat, Zagreb 41000, Croatia. [Kolaric, Branko] Univ Rijeka, Sch Med, Dept Epidemiol & Social Med, Zagreb, Croatia. [Kolaric, Branko] Zagreb Cty Inst Publ Hlth, Publ Hlth Social Med & Gerontol Serv, Zagreb, Croatia. [Vidovic, Vesna] Clin Hosp Ctr Zagreb, Dept Psychol Med, Zagreb, Croatia. [Mollica, Richard Francis] Massachusetts Gen Hosp, Dept Psychiat, Harvard Program Refugee Trauma, Boston, MA 02114 USA. RP Vukovic, IS (reprint author), Andrija Stampar Teaching Inst Publ Hlth, Dept Mental Hlth & Addict Prevent, Mirogojska Cesta 16, HR-10000 Zagreb, Croatia. EM isarajlic26@gmail.com FU National Instiute of Mental Health, Bethesda, Md [MH57806-02] FX Source(s) of research support: This study was supported by grant MH57806-02 from the National Instiute of Mental Health, Bethesda, Md. We are thankful to all participants for sharing their most intimate experiences with us. We acknowledge interviewers, many themselves at that time refugees, who made the data collection possible. NR 50 TC 2 Z9 2 U1 5 U2 5 PU MEDICINSKA NAKLADA PI ZAGREB PA VLASKA 69, HR-10000 ZAGREB, CROATIA SN 0353-5053 J9 PSYCHIAT DANUB JI Psychiatr. Danub. PY 2014 VL 26 SU 3 BP 442 EP 449 PG 8 WC Psychiatry SC Psychiatry GA V44KR UT WOS:000209748400006 PM 25536996 ER PT J AU Bar, M AF Bar, Moshe BE Kveraga, K Bar, M TI The Current Scene SO SCENE VISION: MAKING SENSE OF WHAT WE SEE LA English DT Article; Book Chapter C1 [Bar, Moshe] Bar Ilan Univ, Gonda Multidisciplinary Brain Res Ctr, IL-52100 Ramat Gan, Israel. [Bar, Moshe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Cambridge, MA 02138 USA. RP Bar, M (reprint author), Bar Ilan Univ, Gonda Multidisciplinary Brain Res Ctr, IL-52100 Ramat Gan, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-02785-4 PY 2014 BP 1 EP 3 D2 10.7551/mitpress/9780262027854.001.0001 PG 3 WC Psychology; Psychology, Experimental SC Psychology GA BE5BA UT WOS:000372468300001 ER PT J AU Rajimehr, R Nasr, S Tootell, R AF Rajimehr, Reza Nasr, Shahin Tootell, Roger BE Kveraga, K Bar, M TI Deconstructing Scene Selectivity in Visual Cortex SO SCENE VISION: MAKING SENSE OF WHAT WE SEE LA English DT Article; Book Chapter ID INFERIOR TEMPORAL NEURONS; LATERAL OCCIPITAL CORTEX; MACAQUE CEREBRAL-CORTEX; HUMAN OBJECT AREAS; INFEROTEMPORAL CORTEX; OCCIPITOTEMPORAL CORTEX; PLACE AREA; FIELD MAPS; ORIENTATION; RESPONSES C1 [Rajimehr, Reza] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Nasr, Shahin; Tootell, Roger] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Rajimehr, R (reprint author), MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. NR 68 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-02785-4 PY 2014 BP 73 EP 84 D2 10.7551/mitpress/9780262027854.001.0001 PG 12 WC Psychology; Psychology, Experimental SC Psychology GA BE5BA UT WOS:000372468300005 ER PT J AU Kveraga, K AF Kveraga, Kestutis BE Kveraga, K Bar, M TI Threat Perception in Visual Scenes: Dimensions, Action, and Neural Dynamics SO SCENE VISION: MAKING SENSE OF WHAT WE SEE LA English DT Article; Book Chapter ID MIDBRAIN PERIAQUEDUCTAL GRAY; TOP-DOWN FACILITATION; ORBITOFRONTAL CORTEX; CONTEXTUAL ASSOCIATIONS; PARAHIPPOCAMPAL CORTEX; ALPHA-OSCILLATIONS; PREFRONTAL CORTEX; RHESUS-MONKEY; PATHWAYS; AMYGDALA C1 [Kveraga, Kestutis] Harvard Univ, Dept Radiol, Sch Med, Cambridge, MA 02138 USA. [Kveraga, Kestutis] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Kveraga, K (reprint author), Harvard Univ, Dept Radiol, Sch Med, Cambridge, MA 02138 USA. NR 58 TC 0 Z9 0 U1 1 U2 1 PU MIT PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-02785-4 PY 2014 BP 291 EP 306 D2 10.7551/mitpress/9780262027854.001.0001 PG 16 WC Psychology; Psychology, Experimental SC Psychology GA BE5BA UT WOS:000372468300015 ER PT J AU Cowley, GS Weir, BA Vazquez, F Tamayo, P Scott, JA Rusin, S East-Seletsky, A Ali, LD Gerath, WFJ Pantel, SE Lizotte, PH Jiang, GZ Hsiao, J Tsherniak, A Dwinell, E Aoyama, S Okamoto, M Harrington, W Gelfand, E Green, TM Tomko, MJ Gopal, S Wong, TC Li, HB Howell, S Stransky, N Liefeld, T Pang, D Bistline, J Meyers, BH Armstrong, SA Anderson, KC Stegmaier, K Reich, M Pellman, D Boehm, JS Mesirov, JP Golub, TR Root, DE Hahn, WC AF Cowley, Glenn S. Weir, Barbara A. Vazquez, Francisca Tamayo, Pablo Scott, Justine A. Rusin, Scott East-Seletsky, Alexandra Ali, Levi D. Gerath, William F. J. Pantel, Sarah E. Lizotte, Patrick H. Jiang, Guozhi Hsiao, Jessica Tsherniak, Aviad Dwinell, Elizabeth Aoyama, Simon Okamoto, Michael Harrington, William Gelfand, Ellen Green, Thomas M. Tomko, Mark J. Gopal, Shuba Wong, Terence C. Li, Hubo Howell, Sara Stransky, Nicolas Liefeld, Ted Pang, Dongkeun Bistline, Jonathan Meyers, Barbara Hill Armstrong, Scott A. Anderson, Ken C. Stegmaier, Kimberly Reich, Michael Pellman, David Boehm, Jesse S. Mesirov, Jill P. Golub, Todd R. Root, David E. Hahn, William C. TI Parallel genome-scale loss of function screens in 216 cancer cell lines for the identification of context-specific genetic dependencies SO SCIENTIFIC DATA LA English DT Article AB Using a genome-scale, lentivirally delivered shRNA library, we performed massively parallel pooled shRNA screens in 216 cancer cell lines to identify genes that are required for cell proliferation and/or viability. Cell line dependencies on 11,000 genes were interrogated by 5 shRNAs per gene. The proliferation effect of each shRNA in each cell line was assessed by transducing a population of 11M cells with one shRNA-virus per cell and determining the relative enrichment or depletion of each of the 54,000 shRNAs after 16 population doublings using Next Generation Sequencing. All the cell lines were screened using standardized conditions to best assess differential genetic dependencies across cell lines. When combined with genomic characterization of these cell lines, this dataset facilitates the linkage of genetic dependencies with specific cellular contexts (e.g., gene mutations or cell lineage). To enable such comparisons, we developed and provided a bioinformatics tool to identify linear and nonlinear correlations between these features. C1 [Cowley, Glenn S.; Weir, Barbara A.; Vazquez, Francisca; Tamayo, Pablo; Scott, Justine A.; Rusin, Scott; East-Seletsky, Alexandra; Ali, Levi D.; Gerath, William F. J.; Pantel, Sarah E.; Lizotte, Patrick H.; Jiang, Guozhi; Hsiao, Jessica; Tsherniak, Aviad; Dwinell, Elizabeth; Aoyama, Simon; Okamoto, Michael; Harrington, William; Gelfand, Ellen; Green, Thomas M.; Tomko, Mark J.; Gopal, Shuba; Wong, Terence C.; Howell, Sara; Liefeld, Ted; Pang, Dongkeun; Bistline, Jonathan; Meyers, Barbara Hill; Stegmaier, Kimberly; Reich, Michael; Boehm, Jesse S.; Mesirov, Jill P.; Golub, Todd R.; Root, David E.; Hahn, William C.] Broad Inst Harvard & MIT, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Weir, Barbara A.; Vazquez, Francisca; Anderson, Ken C.; Hahn, William C.] Dana Farber Canc Inst, Dept Med, Boston, MA 02215 USA. [Li, Hubo; Stegmaier, Kimberly; Pellman, David] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Hahn, William C.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02215 USA. [Hahn, William C.] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Stransky, Nicolas] Blueprint Med Inc, Cambridge, MA 02142 USA. [Armstrong, Scott A.] Mem Sloan Kettering, New York, NY 10065 USA. RP Root, DE (reprint author), Broad Inst Harvard & MIT, Cambridge Ctr 7, Cambridge, MA 02142 USA. EM droot@broadinstitute.org; William_Hahn@dfci.harvard.edu FU National Institute Health [U01 CA176058, U54 CA112962]; Achilles consortium FX This work was supported by National Institute Health Grants U01 CA176058 and U54 CA112962 and by the Achilles consortium. NR 25 TC 63 Z9 64 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2052-4463 J9 SCI DATA JI Sci. Data PY 2014 VL 1 AR 140035 DI 10.1038/sdata.2014.35 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V45VG UT WOS:000209843500029 ER PT J AU Sher, DJ Punglia, RS AF Sher, David J. Punglia, Rinaa S. TI Decision Analysis and Cost-Effectiveness Analysis for Comparative Effectiveness Research-A Primer SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID PAINFUL BONE METASTASES; RADIATION-THERAPY; BREAST-CANCER; PROSTATE; HEALTH; RADIOTHERAPY; WOMEN; CARE AB Although the analysis of real-world data is the foundation of comparative effectiveness analysis, not all clinical questions are easily approached with patient-derived information. Decision analysis is a set of modeling and analytic tools that simulate treatment and disease processes, including the incorporation of patient preferences, thus generating optimal treatment strategies for varying patient, disease, and treatment conditions. Although decision analysis is informed by evidence-derived outcomes, its ability to test treatment strategies under different conditions that are realistic but not necessarily reported in the literature makes it a useful and complementary technique to more standard data analysis. Similarly, cost-effectiveness analysis is a discipline in which the relative costs and benefits of treatment alternatives are rigorously compared. With the well-recognized increase in highly technical, costly radiation therapy technologies, the cost-effectiveness of these different treatments would come under progressively more scrutiny. In this review, we discuss the theoretical and practical aspects of decision analysis and cost-effectiveness analysis, providing examples that highlight their methodology and utility. (C) 2014 Elsevier Inc. All rights reserved. C1 [Sher, David J.] Rush Univ, Med Ctr, Dept Radiat Oncol, Chicago, IL 60612 USA. [Punglia, Rinaa S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Sher, DJ (reprint author), Rush Univ, Med Ctr, Dept Radiat Oncol, Chicago, IL 60612 USA. EM david_sher@rush.edu NR 25 TC 4 Z9 4 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 2014 VL 24 IS 1 BP 14 EP 24 DI 10.1016/j.semradonc.2013.08.002 PG 11 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 268PI UT WOS:000328182600003 PM 24314338 ER PT J AU Chen, AB AF Chen, Aileen B. TI Comparative Effectiveness Research in Radiation Oncology: Assessing Technology SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID CELL LUNG-CANCER; INTENSITY-MODULATED RADIOTHERAPY; LOCALIZED PROSTATE-CANCER; PALLIATIVE THORACIC RADIOTHERAPY; RANDOMIZED CONTROLLED-TRIAL; PROTON THERAPY; CONFORMAL RADIOTHERAPY; PLANNING COMPLEXITY; INITIAL TREATMENT; DOSE-ESCALATION AB Technological advances are a major contributor to rising costs in health care, including radiation oncology. Despite the large amount spent on new technologies, technology assessment remains inadequate, leading to potentially costly and unnecessary use of new technologies. Comparative effectiveness studies have an important role to play in evaluating the benefits and harms of new technologies compared with older technologies and have been identified as a priority area for research by the Radiation Oncology Institute. This article outlines the elements of effective technology assessment, identifies key challenges to comparative effectiveness studies of new radiation oncology technologies, and reviews several examples of comparative effectiveness studies in radiation oncology, including studies on conformal radiation, IMRT, proton therapy, and other concurrent new technologies. (C) 2014 Elsevier Inc. All rights reserved. C1 [Chen, Aileen B.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. [Chen, Aileen B.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. RP Chen, AB (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,D1111, Boston, MA 02215 USA. EM achen7@partners.org OI Chen, Aileen/0000-0002-5385-3360 NR 74 TC 12 Z9 12 U1 0 U2 15 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1053-4296 EI 1532-9461 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD JAN PY 2014 VL 24 IS 1 BP 25 EP 34 DI 10.1016/j.semradonc.2013.08.003 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 268PI UT WOS:000328182600004 PM 24314339 ER PT S AU Fu, YF Reyon, D Joung, JK AF Fu, Yanfang Reyon, Deepak Joung, J. Keith BE Doudna, JA Sontheimer, EJ TI Targeted Genome Editing in Human Cells Using CRISPR/Cas Nucleases and Truncated Guide RNAs SO USE OF CRISPR/CAS9, ZFNS, AND TALENS IN GENERATING SITE-SPECIFIC GENOME ALTERATIONS SE Methods in Enzymology LA English DT Review; Book Chapter ID CONDITIONAL ALLELES; CAS9; SPECIFICITY; SYSTEMS; ZEBRAFISH; ENDONUCLEASE AB CRISPR RNA-guided nucleases have recently emerged as a robust genome-editing platform that functions in a wide range of organisms. To reduce off-target effects of these nucleases, we developed and validated a modified system that uses truncated guide RNAs (tru-gRNAs). The use of tru-gRNAs leads to decreases in off-target effects and does not generally compromise the on-target efficiencies of these genome-editing nucleases. In this chapter, we describe guidelines for identifying potential tru-gRNA target sites and protocols for measuring the on-target efficiencies of CRISPR RNA-guided nucleases in human cells. C1 [Fu, Yanfang; Reyon, Deepak; Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Ctr Computat & Integrat Biol, Charlestown, MA 02129 USA. [Fu, Yanfang; Reyon, Deepak; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. [Fu, Yanfang; Reyon, Deepak; Joung, J. Keith] Harvard Med Sch, Dept Pathol, Boston, MA USA. RP Joung, JK (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Ctr Computat & Integrat Biol, Charlestown, MA 02129 USA. EM jjoung@mgh.harvard.edu NR 36 TC 9 Z9 10 U1 1 U2 6 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-801185-0 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2014 VL 546 BP 21 EP 45 DI 10.1016/B978-0-12-801185-0.00002-7 PG 25 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell & Tissue Engineering SC Biochemistry & Molecular Biology; Cell Biology GA BF5HW UT WOS:000382008600003 PM 25398334 ER PT S AU Pattanayak, V Guilinger, JP Liu, DR AF Pattanayak, Vikram Guilinger, John P. Liu, David R. BE Doudna, JA Sontheimer, EJ TI Determining the Specificities of TALENs, Cas9, and Other Genome-Editing Enzymes SO USE OF CRISPR/CAS9, ZFNS, AND TALENS IN GENERATING SITE-SPECIFIC GENOME ALTERATIONS SE Methods in Enzymology LA English DT Review; Book Chapter ID ZINC-FINGER NUCLEASES; DNA-BINDING SPECIFICITIES; ARTIFICIAL TRANSCRIPTION FACTORS; CONTROLLING GENE-EXPRESSION; DOUBLE-STRAND BREAKS; ENDONUCLEASE I-SCEL; OFF-TARGET SITES; EFFECTOR NUCLEASES; HUMAN-CELLS; DIRECTED EVOLUTION AB The rapid development of programmable site-specific endonucleases has led to a dramatic increase in genome engineering activities for research and therapeutic purposes. Specific loci of interest in the genomes of a wide range of organisms including mammals can now bemodified using zinc-finger nucleases, transcription activator-like effectornucleases, and CRISPR-associated Cas9 endonucleases in a site-specific manner, in some cases requiring relatively modest effort for endonuclease design, construction, and application. While these technologies have made genome engineering widely accessible, the ability of programmable nucleases to cleave off-target sequences can limit their applicability and raise concerns about therapeutic safety. In this chapter, we review methods to evaluate and improve the DNA cleavage activity of programmable site-specific endonucleases and describe a procedure for a comprehensive off-target profiling method based on the in vitro selection of very large (similar to 10(12)-membered) libraries of potential nuclease substrates. C1 [Pattanayak, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Guilinger, John P.; Liu, David R.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Guilinger, John P.; Liu, David R.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. RP Liu, DR (reprint author), Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. EM drliu@fas.harvard.edu FU Howard Hughes Medical Institute; NIGMS NIH HHS [R01 GM095501, T32 GM007753, T32GM007753] NR 103 TC 16 Z9 20 U1 6 U2 13 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-801185-0 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2014 VL 546 BP 47 EP 78 DI 10.1016/B978-0-12-801185-0.00003-9 PG 32 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell & Tissue Engineering SC Biochemistry & Molecular Biology; Cell Biology GA BF5HW UT WOS:000382008600004 PM 25398335 ER PT S AU Meissner, TB Mandal, PK Ferreira, LMR Rossi, DJ Cowan, CA AF Meissner, Torsten B. Mandal, Pankaj K. Ferreira, Leonardo M. R. Rossi, Derrick J. Cowan, Chad A. BE Doudna, JA Sontheimer, EJ TI Genome Editing for Human Gene Therapy SO USE OF CRISPR/CAS9, ZFNS, AND TALENS IN GENERATING SITE-SPECIFIC GENOME ALTERATIONS SE Methods in Enzymology LA English DT Review; Book Chapter ID HEMATOPOIETIC STEM-CELLS; ZINC-FINGER NUCLEASES; T-CELLS; MESSENGER-RNA; IN-VIVO; BETA-2-MICROGLOBULIN; HIV-1; CCR5; CRISPR-CAS9; MICE AB The rapid advancement of genome-editing techniques holds much promise for the field of human gene therapy. From bacteria to model organisms and human cells, genome editing tools such as zinc-finger nucleases (ZNFs), TALENs, and CRISPR/Cas9 have been successfully used to manipulate the respective genomes with unprecedented precision. With regard to human gene therapy, it is of great interest to test the feasibility of genome editing in primary human hematopoietic cells that could potentially be used to treat a variety of human genetic disorders such as hemoglobinopathies, primary immunodeficiencies, and cancer. In this chapter, we explore the use of the CRISPR/Cas9 system for the efficient ablation of genes in two clinically relevant primary human cell types, CD4+ T cells and CD34+ hematopoietic stem and progenitor cells. By using two guide RNAs directed at a single locus, we achieve highly efficient and predictable deletions that ablate gene function. The use of a Cas9-2A-GFP fusion protein allows FACS-based enrichment of the transfected cells. The ease of designing, constructing, and testing guide RNAs makes this dual guide strategy an attractive approach for the efficient deletion of clinically relevant genes in primary human hematopoietic stem and effector cells and enables the use of CRISPR/Cas9 for gene therapy. C1 [Meissner, Torsten B.; Mandal, Pankaj K.; Ferreira, Leonardo M. R.; Rossi, Derrick J.; Cowan, Chad A.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Mandal, Pankaj K.; Rossi, Derrick J.] Boston Childrens Hosp, Div Hematol Oncol, Program Cellular & Mol Med, Boston, MA USA. [Rossi, Derrick J.] Harvard Med Sch, Dept Pediat, Boston, MA USA. [Rossi, Derrick J.; Cowan, Chad A.] Sherman Fairchild Biochem, Harvard Stem Cell Inst, Cambridge, MA USA. [Cowan, Chad A.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. RP Cowan, CA (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. EM chad_cowan@harvard.edu OI Ferreira, Leonardo/0000-0003-2491-9866 NR 41 TC 7 Z9 8 U1 3 U2 10 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-801185-0 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2014 VL 546 BP 273 EP 295 DI 10.1016/B978-0-12-801185-0.00013-1 PG 23 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell & Tissue Engineering SC Biochemistry & Molecular Biology; Cell Biology GA BF5HW UT WOS:000382008600014 PM 25398345 ER PT S AU Gonzales, APW Yeh, JRJ AF Gonzales, Andrew P. W. Yeh, Jing-Ruey Joanna BE Doudna, JA Sontheimer, EJ TI Cas9-Based Genome Editing in Zebrafish SO USE OF CRISPR/CAS9, ZFNS, AND TALENS IN GENERATING SITE-SPECIFIC GENOME ALTERATIONS SE Methods in Enzymology LA English DT Review; Book Chapter ID ZINC-FINGER NUCLEASES; CRISPR-CAS SYSTEMS; RNA-GUIDED ENDONUCLEASES; PROVIDES ACQUIRED-RESISTANCE; ONE-STEP GENERATION; HUMAN-CELLS; ADAPTIVE IMMUNITY; HOMOLOGOUS RECOMBINATION; HUMAN-DISEASE; STREPTOCOCCUS-THERMOPHILUS AB Genome editing using the Cas9 endonuclease of Streptococcus pyogenes has demonstrated unprecedented efficacy and facility in a wide variety of biological systems. In zebrafish, specifically, studies have shown that Cas9 can be directed to user-defined genomic target sites via synthetic guide RNAs, enabling random or homology-directed sequence alterations, long-range chromosomal deletions, simultaneous disruption of multiple genes, and targeted integration of several kilobases of DNA. Altogether, these methods are opening new doors for the engineering of knock-outs, conditional alleles, tagged proteins, reporter lines, and disease models. In addition, the ease and high efficiency of generating Cas9-mediated gene knock-outs provides great promise for high-throughput functional genomics studies in zebrafish. In this chapter, we briefly review the origin of CRISPR/Cas technology and discuss current Cas9-based genome-editing applications in zebrafish with particular emphasis on their designs and implementations. C1 [Gonzales, Andrew P. W.; Yeh, Jing-Ruey Joanna] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. [Gonzales, Andrew P. W.; Yeh, Jing-Ruey Joanna] Harvard Med Sch, Dept Med, Boston, MA USA. RP Yeh, JRJ (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. EM jyeh1@mgh.harvard.edu FU NCI NIH HHS [R01 CA140188]; NIGMS NIH HHS [R01 GM088040] NR 136 TC 12 Z9 14 U1 4 U2 10 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-801185-0 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2014 VL 546 BP 377 EP 413 DI 10.1016/B978-0-12-801185-0.00018-0 PG 37 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell & Tissue Engineering SC Biochemistry & Molecular Biology; Cell Biology GA BF5HW UT WOS:000382008600019 PM 25398350 ER PT S AU Li, JF Zhang, DD Sheen, J AF Li, Jian-Feng Zhang, Dandan Sheen, Jen BE Doudna, JA Sontheimer, EJ TI Cas9-Based Genome Editing in Arabidopsis and Tobacco SO USE OF CRISPR/CAS9, ZFNS, AND TALENS IN GENERATING SITE-SPECIFIC GENOME ALTERATIONS SE Methods in Enzymology LA English DT Review; Book Chapter ID TARGETED MUTAGENESIS; GENE-EXPRESSION; GUIDE RNA; PLANTS; CAS9; ENDONUCLEASE; MULTIPLEX; SYSTEM; ZFN AB Targeted modification of plant genome is key to elucidating and manipulating gene functions in plant research and biotechnology. The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) technology is emerging as a powerful genome-editing method in diverse plants that traditionally lacked facile and versatile tools for targeted genetic engineering. This technology utilizes easily reprogrammable guide RNAs (sgRNAs) to direct Streptococcus pyogenes Cas9 endonuclease to generate DNA double-stranded breaks in targeted genome sequences, which facilitates efficient mutagenesis by error-prone nonhomologous end-joining (NHEJ) or sequence replacement by homology-directed repair (HDR). In this chapter, we describe the procedure to design and evaluate dual sgRNAs for plant codon-optimized Cas9-mediated genome editing using mesophyll protoplasts as model cell systems in Arabidopsis thaliana and Nicotiana benthamiana. We also discuss future directions in sgRNA/Cas9 applications for generating targeted genome modifications and gene regulations in plants. C1 [Li, Jian-Feng; Zhang, Dandan; Sheen, Jen] Massachusetts Gen Hosp, Dept Mol Biol, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Li, Jian-Feng; Zhang, Dandan; Sheen, Jen] Harvard Med Sch, Dept Genet, Boston, MA USA. RP Li, JF (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. EM lijfeng3@mail.sysu.edu.cn FU NIGMS NIH HHS [R01 GM60493, R01 GM70567] NR 22 TC 9 Z9 12 U1 11 U2 21 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-801185-0 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2014 VL 546 BP 459 EP 472 DI 10.1016/B978-0-12-801185-0.00022-2 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell & Tissue Engineering SC Biochemistry & Molecular Biology; Cell Biology GA BF5HW UT WOS:000382008600022 PM 25398353 ER PT J AU Sedaghat, AR Cunningham, MJ Busaba, NY AF Sedaghat, Ahmad R. Cunningham, Michael J. Busaba, Nicholas Y. TI Connexin 32 and 43 mutations: Do they play a role in chronic rhinosinusitis? SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article ID NASAL EPITHELIAL-CELLS; HEARING IMPAIRMENT; INNATE IMMUNITY; DISEASE; GAP; PATHOGENESIS; DIAGNOSIS; JUNCTIONS AB Objective: Dysfunction of the sinonasal epithelium may contribute to the pathogenesis of chronic rhinosinusitis (CRS) including recurrent acute rhinosinusitis (RARS). Mutations in connexin 32 and 43 proteins have been associated with a number of human diseases. The objective of this study is to investigate the role of mutations in connexin 32 or connexin 43 genes in CRS and RARS. Methods: Prospective case series of 19 patients with CRS and /or BARS. Clinical and demographic factors were noted and buccal swabs were collected for DNA sequencing of connexin 32 and connexin 43 genes. Results: One patient was found to have a conservative V193I mutation in the connexin 32 gene. Connexin 43 mutations were found in two patients - a silent R239R mutation and an AAA insertion after the stop codon in the 3' UTR. None of these mutations are associated with any known diseases or predicted to lead to protein dysfunction. Conclusion: Mutations in connexin 32 or 43 genes in patients with CRS, including BARS, appear to be rare. The etiologic role of connexin mutations in chromic rhinosinusitis is suspect, and routine sequencing for connexin mutations in patients with BARS or CRS is not cost effective. Published by Elsevier Inc. C1 [Sedaghat, Ahmad R.; Busaba, Nicholas Y.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Cunningham, Michael J.] Childrens Hosp, Dept Otolaryngol & Commun Enhancement, Boston, MA 02115 USA. [Busaba, Nicholas Y.] VA Boston HealthCare Syst, Div Otolaryngol, Boston, MA USA. [Sedaghat, Ahmad R.; Cunningham, Michael J.; Busaba, Nicholas Y.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Busaba, NY (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM nicolas_busaba@meei.harvard.edu NR 24 TC 1 Z9 1 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0196-0709 EI 1532-818X J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD JAN-FEB PY 2014 VL 35 IS 1 BP 33 EP 36 DI 10.1016/j.amjoto.2013.08.008 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 266FD UT WOS:000328007900006 PM 24119489 ER PT J AU Dzierzewski, JM AF Dzierzewski, Joseph M. TI Diversity in Late Life: Definitions, Implications, and Considerations INTRODUCTION SO CLINICAL GERONTOLOGIST LA English DT Editorial Material ID PSYCHOLOGY C1 [Dzierzewski, Joseph M.] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. [Dzierzewski, Joseph M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Dzierzewski, JM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, 16111 Plummer St 11E, North Hills, CA 91343 USA. EM Joseph.Dzierzewski@va.gov NR 4 TC 0 Z9 0 U1 0 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0731-7115 EI 1545-2301 J9 CLIN GERONTOLOGIST JI Clin. Gerontol. PD JAN 1 PY 2014 VL 37 IS 1 SI SI BP 1 EP 3 DI 10.1080/07317115.2014.847308 PG 3 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 259FK UT WOS:000327512600001 ER PT J AU Ren, Y Lin, WL Sanchez, L Ceballos, C Polydoro, M Spires-Jones, TL Hyman, BT Dickson, DW Sahara, N AF Ren, Yan Lin, Wen-Lang Sanchez, Laura Ceballos, Carolina Polydoro, Manuela Spires-Jones, Tara L. Hyman, Bradley T. Dickson, Dennis W. Sahara, Naruhiko TI Endogenous Tau Aggregates in Oligodendrocytes of rTg4510 Mice Induced by Human P301L Tau SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Antibody; mouse tau; oligodendrocytes; tau protein; tauopathy; transgenic mice ID PAIRED HELICAL FILAMENTS; TRANSGENIC MOUSE MODELS; ALZHEIMERS-DISEASE; NEURONAL LOSS; TAUOPATHY; PATHOLOGY; BRAIN; PROPAGATION; PROTEIN; MEMORY AB Tau belongs to the microtubule-associated family of proteins that maintain cytoskeletal structure by regulating microtubule dynamics. In certain neurodegenerative diseases termed tauopathies, tau is abnormally phosphorylated and accumulates as filamentous inclusions. Transgenic mouse models that overexpress human tau have been widely used to investigate tau pathogenesis. Although many studies have attempted to elucidate the pathological function of transgenic human tau, it remains unknown whether endogenous mouse tau is involved in disease progression. Here we generated an mTau antibody that selectively recognizes mouse and rat tau, but not human tau. In rTg4510 tau transgenic mice, we identified a higher molecular weight mouse tau (similar to 60-kDa) in sarkosyl-insoluble fractions. mTau antibody started to recognize intracellular aggregates and thread-like structures in 4- to 6-month-old rTg4510 mice. Tau inclusions appeared earlier, being detected in 2.5-month-old rTg4510 mice with MC1 antibody. Immunoelectron microscopy confirmed the presence of filamentous aggregates of mouse tau, which were abundant in oligodendrocytes but rare in neurons. Mouse tau inclusions in oligodendrocytes were confirmed by double-labeling with an oligodendrocyte marker. Our data indicate that mouse tau has potential aggregation properties in neurons and non-neurons. The mTau antibody will be useful for investigating the role of mouse tau in mouse models of tauopathy. C1 [Ren, Yan; Ceballos, Carolina; Sahara, Naruhiko] Univ Florida, Dept Neurosci, Ctr Translat Res Neurodegenerat Dis, Gainesville, FL 32610 USA. [Lin, Wen-Lang; Dickson, Dennis W.] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. [Sanchez, Laura; Polydoro, Manuela; Spires-Jones, Tara L.; Hyman, Bradley T.] Harvard Univ, MassGen Inst Neurodegenerat Dis, Dept Neurol,Alzheimers Dis Res Lab, Massachusetts Gen Hosp,Med Sch, Charlestown, MA USA. RP Sahara, N (reprint author), Univ Florida, Dept Neurosci, Ctr Translat Res Neurodegenerat Dis, Gainesville, FL 32610 USA. EM nsahara@nirs.go.jp OI Dickson, Dennis W/0000-0001-7189-7917 FU National Institutes of Health/National Institute of Neurological Diseases and Stroke [R21 NS067127]; University of Florida FX The authors thank Dr. Lester I. Binder (Northwestern University Medical School) for providing the monoclonal anti-tau antibodies Tau5 and Tau12; Dr. Peter Davies (Albert Einstein University) for the monoclonal anti-tau antibodies CP13, MC1 and PHF1; Dr. Shu-Hui Yen (Mayo Clinic Jacksonville) for the polyclonal anti-human tau antibody E1; Linda Rousseau (Mayo Clinic) and Virginia Phillips (Mayo Clinic) for histologic support; and Monica Castanedes-Casey (Mayo Clinic) for immunohistochemistry support. The authors also thank Dr. Jada Lewis (University of Florida) for helpful discussions. This research was supported by Grant R21 NS067127 from the National Institutes of Health/National Institute of Neurological Diseases and Stroke (N.S.) and the Thomas H. Maren Junior Investigator Fund from the University of Florida (N.S.). NR 46 TC 1 Z9 1 U1 1 U2 8 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2014 VL 38 IS 3 BP 589 EP 600 DI 10.3233/JAD-130986 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 260MH UT WOS:000327598500012 PM 24028867 ER PT J AU Razlighi, QR Stallard, E Brandt, J Blacker, D Albert, M Scarmeas, N Kinosian, B Yashin, AI Stern, Y AF Razlighi, Qolamreza R. Stallard, Eric Brandt, Jason Blacker, Deborah Albert, Marilyn Scarmeas, Nikolaos Kinosian, Bruce Yashin, Anatoliy I. Stern, Yaakov TI A New Algorithm for Predicting Time to Disease Endpoints in Alzheimer's Disease Patients SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; full-time care; grade of membership model; nursing home; prediction algorithm; time to death ID PROGRESSION; MODEL; CARE AB Background: The ability to predict the length of time to death and institutionalization has strong implications for Alzheimer's disease patients and caregivers, health policy, economics, and the design of intervention studies. Objective: To develop and validate a prediction algorithm that uses data from a single visit to estimate time to important disease endpoints for individual Alzheimer's disease patients. Method: Two separate study cohorts (Predictors 1, N=252; Predictors 2, N=254), all initially with mild Alzheimer's disease, were followed for 10 years at three research centers with semiannual assessments that included cognition, functional capacity, and medical, psychiatric, and neurologic information. The prediction algorithm was based on a longitudinal Grade of Membership model developed using the complete series of semiannually-collected Predictors 1 data. The algorithm was validated on the Predictors 2 data using data only from the initial assessment to predict separate survival curves for three outcomes. Results: For each of the three outcome measures, the predicted survival curves fell well within the 95% confidence intervals of the observed survival curves. Patients were also divided into quintiles for each endpoint to assess the calibration of the algorithm for extreme patient profiles. In all cases, the actual and predicted survival curves were statistically equivalent. Predictive accuracy was maintained even when key baseline variables were excluded, demonstrating the high resilience of the algorithm to missing data. Conclusion: The new prediction algorithm accurately predicts time to death, institutionalization, and need for full-time care in individual Alzheimer's disease patients; it can be readily adapted to predict other important disease endpoints. The algorithm will serve an unmet clinical, research, and public health need. C1 [Razlighi, Qolamreza R.; Scarmeas, Nikolaos; Stern, Yaakov] Columbia Univ Coll Phys & Surg, Dept Neurol, Cognit Neurosci Div, New York, NY 10032 USA. [Stallard, Eric; Yashin, Anatoliy I.] Duke Univ, Social Sci Res Inst, Durham, NC USA. [Stallard, Eric; Yashin, Anatoliy I.] Duke Univ, Ctr Populat Hlth & Aging, Durham, NC USA. [Brandt, Jason; Albert, Marilyn] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Brandt, Jason; Albert, Marilyn] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Brandt, Jason] Copper Ridge Inst, Sykesville, MD USA. [Blacker, Deborah] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Dept Psychiat,Massachusetts Gen Hosp,Harvard Med, Boston, MA 02115 USA. [Kinosian, Bruce] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Stern, Y (reprint author), 630W 168th St,P&S Box 16, New York, NY 10032 USA. EM ys11@columbia.edu OI Brandt, Jason/0000-0001-7381-6244 FU National Institute on Aging [R01-AG07370] FX The Predictors Study is supported by a grant to Dr. Stern from the National Institute on Aging, grant R01-AG07370. Doctors Stern and Razlighi 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 17 TC 3 Z9 3 U1 0 U2 9 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2014 VL 38 IS 3 BP 661 EP 668 DI 10.3233/JAD-131142 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 260MH UT WOS:000327598500018 PM 24064468 ER PT J AU Castro, CM Ghazani, AA Chung, J Shao, HL Issadore, D Yoon, TJ Weissleder, R Lee, H AF Castro, Cesar M. Ghazani, Arezou A. Chung, Jaehoon Shao, Huilin Issadore, David Yoon, Tae-Jong Weissleder, Ralph Lee, Hakho TI Miniaturized nuclear magnetic resonance platform for detection and profiling of circulating tumor cells SO LAB ON A CHIP LA English DT Review ID METASTATIC BREAST-CANCER; CORE-SHELL NANOPARTICLES; BIOORTHOGONAL CHEMISTRY; RAPID DETECTION; LUNG-CANCER; RELAXATION; PARTICLES; BACTERIA; SYSTEM; NMR AB Accurate detection and profiling of circulating tumor cells (CTCs) is a highly sought after technology to improve cancer management. Such "liquid biopsies" could offer a non-invasive, repeatable window into each patient's tumor, facilitating early cancer diagnosis and treatment monitoring. The rarity of CTCs, approximated at 1 CTC for every billion peripheral blood cells, however, poses significant challenges to sensitive and reliable detection. We have recently developed a new micro-nuclear magnetic resonance (mu NMR) platform for biosensing. Through the synergistic integration of microfabrication, nanosensors, and novel chemistries, the mu NMR platform offers high detection sensitivity and point-of-care operation, overcoming technical barriers in CTC research. We herein review the mu NMR technology with emphasis on its application to CTC detection. Recent advances in the sensing technology will be summarized, followed by the description of the dynamic interplay between our preclinical and clinical CTC studies. C1 [Castro, Cesar M.; Ghazani, Arezou A.; Chung, Jaehoon; Shao, Huilin; Issadore, David; Yoon, Tae-Jong; Weissleder, Ralph; Lee, Hakho] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Castro, Cesar M.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Dept Syst Biol, Sch Med, Boston, MA 02114 USA. RP Castro, CM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. EM Castro.Cesar@mgh.harvard.edu; hlee@mgh.harvard.edu RI Issadore, David/L-8451-2014 FU B.S.-Ph.D. National Science Scholarship; Agency for Science, Technology and Research, Singapore; NIH [R01EB004626, R01EB010011, HHSN268201000044C, R01HL113156, U54-CA119349, K12CA087723-10, T32-CA79443] FX The authors thank N. Sergeyev for providing dextran-coated iron oxide nanoparticles; Y. Fisher-Jeffes for reviewing the manuscript; R. M. Westervelt (Harvard) for helpful discussion; Ham group (Harvard) for implementing CMOS ICs. H. Shao acknowledges financial support from the B.S.-Ph.D. National Science Scholarship awarded by the Agency for Science, Technology and Research, Singapore. This work was supported in part by NIH Grants (R01EB004626, R01EB010011, HHSN268201000044C, R01HL113156, U54-CA119349, K12CA087723-10, and T32-CA79443). NR 51 TC 19 Z9 20 U1 7 U2 102 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 EI 1473-0189 J9 LAB CHIP JI Lab Chip PY 2014 VL 14 IS 1 BP 14 EP 23 DI 10.1039/c3lc50621e PG 10 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 261MK UT WOS:000327669000002 PM 23835814 ER PT J AU Mueller-Pfeiffer, C Zeffiro, T O'Gorman, R Michels, L Baumann, P Wood, N Spring, J Rufer, M Pitman, RK Orr, SP AF Mueller-Pfeiffer, Christoph Zeffiro, Thomas O'Gorman, Ruth Michels, Lars Baumann, Peter Wood, Nellie Spring, Justin Rufer, Michael Pitman, Roger K. Orr, Scott P. TI Cortical and cerebellar modulation of autonomic responses to loud sounds SO PSYCHOPHYSIOLOGY LA English DT Article DE Functional magnetic resonance imaging; Unconditioned response; Heart rate; Skin conductance; Saliency; Autonomic nervous system ID POSTTRAUMATIC-STRESS-DISORDER; CHILDHOOD SEXUAL-ABUSE; SKIN-CONDUCTANCE RESPONSES; ANTERIOR CINGULATE CORTEX; SCRIPT-DRIVEN IMAGERY; CEREBRAL-BLOOD-FLOW; PHYSIOLOGICAL-RESPONSES; STARTLING TONES; INSULAR CORTEX; HUMAN BRAIN AB Detecting unexpected environmental change causes modulation of autonomic activity essential for survival. Understanding the neural mechanisms associated with responses to loud sounds may provide insights into the pathophysiology of posttraumatic stress disorder (PTSD), since individuals with PTSD exhibit heightened autonomic responses to unexpected loud sounds. We combined fMRI with autonomic psychophysiological assessment to investigate central and peripheral reactivity to loud tones in 20 healthy participants. Activity in anterior insula, pregenual anterior cingulate cortex, anterior midcingulate cortex, supplementary motor area, supramarginal gyrus, and cerebellar lobules VIII-IX was associated with both tones and concomitant skin conductance responses. Since regions signaling unexpected external events modulate autonomic activity, heightened loud tone autonomic responses in PTSD may reflect sensitization of this salience network. C1 [Mueller-Pfeiffer, Christoph; Baumann, Peter; Rufer, Michael] Univ Zurich Hosp, Dept Psychiat & Psychotherapy, CH-8091 Zurich, Switzerland. [Mueller-Pfeiffer, Christoph] Ctr Educ & Res COEUR, Psychiat Serv Cty St Gallen North, Wil, Switzerland. [Mueller-Pfeiffer, Christoph; Wood, Nellie; Spring, Justin; Pitman, Roger K.; Orr, Scott P.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Mueller-Pfeiffer, Christoph; Wood, Nellie; Spring, Justin; Pitman, Roger K.; Orr, Scott P.] Harvard Univ, Sch Med, Boston, MA USA. [Zeffiro, Thomas] Massachusetts Gen Hosp, Neural Syst Grp, Boston, MA 02114 USA. [O'Gorman, Ruth] Univ Childrens Hosp Zurich, Ctr MR Res, Zurich, Switzerland. [Michels, Lars] Univ Zurich Hosp, Inst Neuroradiol, CH-8091 Zurich, 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 OI Rufer, Michael/0000-0003-4964-4213; O'Gorman, Ruth/0000-0001-5932-7786 FU Fonds fur wissenschaftliche Zwecke im Interesse der Heilung von Geisteskrankheiten," Zurich; Department of Psychiatry and Psychotherapy, University Hospital Zurich, Zurich, Switzerland FX The study was funded by the "Fonds fur wissenschaftliche Zwecke im Interesse der Heilung von Geisteskrankheiten," Zurich, and the Department of Psychiatry and Psychotherapy, University Hospital Zurich, Zurich, Switzerland. NR 72 TC 3 Z9 3 U1 7 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD JAN PY 2014 VL 51 IS 1 BP 60 EP 69 DI 10.1111/psyp.12142 PG 10 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 267BX UT WOS:000328071500006 PM 24016238 ER PT J AU Martin, MY Fouad, MN Oster, RA Schrag, D Urmie, J Sanders, S Pisu, M AF Martin, Michelle Y. Fouad, Mona N. Oster, Robert A. Schrag, Deborah Urmie, Julie Sanders, Sara Pisu, Maria TI What do cancer patients worry about when making decisions about treatment? Variation across racial/ethnic groups SO SUPPORTIVE CARE IN CANCER LA English DT Article DE Cancer; Worry; Supportive; Care ID CARE OUTCOMES RESEARCH; BREAST-CANCER; OLDER-ADULTS; COLORECTAL-CANCER; HEALTH; SURVIVORS; TRANSPORTATION; PERSPECTIVE; NAVIGATION; AGE AB The aim of this study was to determine the issues patients worry about when making decisions about cancer treatment. A total of 5,044 colorectal and lung cancer patients from the Cancer Care Outcomes Research and Surveillance Consortium reported their level of worry about (1) treatment side effects, (2) treatment costs, (3) time away from family, (4) time away from work, and (5) transportation to treatment sites. Using multivariable logistic regression, we evaluated the association of sociodemographic, clinical, and psychosocial variables with worry. Overall, 75 % of patients worried about side effects of treatments; 40 %, the cost of treatment; 50 %, time away from family; 52 %, time away from work; and 22 %, about transportation. In multivariable analyses, across all worry domains, older patients had lower odds of reporting worry (p values < 0.001). Patients who perceived less than excellent quality of care, self-assessed their health as less than excellent, and those with a higher cancer stage were more likely to report worry. Asian patients were more likely to report worry than Whites about the cost of treatment and transportation, and relative to Whites, Hispanics were more likely to report worry about transportation (p values < 0.05). Black patients were less likely to report worry about time away from work. Patients worry about issues beyond treatment side effects when making treatment decisions. The pattern of worry varies along sociodemographic, clinical, and psychosocial factors, including race and ethnicity. Understanding the source of patient worry and identifying interventions to alleviate worry are important to delivering patient-centered cancer care. C1 [Martin, Michelle Y.; Fouad, Mona N.; Oster, Robert A.; Pisu, Maria] Univ Alabama Birmingham, Dept Med, Div Prevent Med, Birmingham, AL 35205 USA. [Schrag, Deborah] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Urmie, Julie] Univ Iowa, Dept Pharm Practice & Sci, Div Hlth Serv Res, Iowa City, IA 52242 USA. [Sanders, Sara] Univ Iowa, Sch Social Work, Iowa City, IA 52242 USA. RP Martin, MY (reprint author), Univ Alabama Birmingham, Dept Med, Div Prevent Med, 1717 11th Ave South,MT 617, Birmingham, AL 35205 USA. EM mymartin@uab.edu FU National Cancer Institute (NCI) [U01 CA093344]; NCI; Dana-Farber Cancer Institute/Cancer Research Network [U01 CA093332]; Harvard Medical School/Northern California Cancer Center [U01 CA093324, RAND/UCLA U01 CA093348]; University of Alabama at Birmingham [U01 CA093329, P30 AG031054]; University of Iowa [U01 CA. 093339]; University of North Carolina [U01 CA 093326]; Department of Veterans Affairs grant [CRS 02-164]; Morehouse School of Medicine/Tuskegee University/University of Alabama Cancer Center Partnership [U54CA118948] FX The CanCORS consortium was supported by grants from the National Cancer Institute (NCI) to the Statistical Coordinating Center (U01 CA093344) and the NCI-supported Primary Data Collection and Research Centers (Dana-Farber Cancer Institute/Cancer Research Network U01 CA093332, Harvard Medical School/Northern California Cancer Center U01 CA093324, RAND/UCLA U01 CA093348,University of Alabama at Birmingham U01 CA093329, University of Iowa U01 CA. 093339, University of North Carolina U01 CA 093326) and by a Department of Veterans Affairs grant to the Durham VA Medical Center CRS 02-164. Morehouse School of Medicine/Tuskegee University/University of Alabama Cancer Center Partnership U54CA118948, University of Alabama at Birmingham P30 AG031054. NR 28 TC 9 Z9 9 U1 2 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0941-4355 EI 1433-7339 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD JAN PY 2014 VL 22 IS 1 BP 233 EP 244 DI 10.1007/s00520-013-1958-5 PG 12 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA 264QL UT WOS:000327895000029 PM 24037412 ER PT J AU Tai, YT Anderson, KC AF Tai, Yu-Tzu Anderson, Kenneth C. BE Schey, SA Yong, KL Marcus, R Anderson, KC TI Principles of pathway directed therapy SO MYELOMA: PATHOLOGY, DIAGNOSIS, AND TREATMENT LA English DT Article; Book Chapter ID MULTIPLE-MYELOMA CELLS; SHOCK-PROTEIN 90; MEK1/2 INHIBITOR; ANTITUMOR-ACTIVITY; NUCLEAR EXPORT; BREAST-CANCER; BONE-MARROW; OPEN-LABEL; PHASE-II; IN-VITRO C1 [Tai, Yu-Tzu] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Boston, MA USA. [Anderson, Kenneth C.] Dana Farber Canc Inst, Kraft Family Blood Donor Ctr, Boston, MA 02115 USA. RP Tai, YT (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. NR 52 TC 1 Z9 1 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-1-107-01057-4 PY 2014 BP 110 EP 120 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA BIB06 UT WOS:000327193500009 ER PT J AU Streetly, MJ Laubach, J Richardson, P Schey, SA AF Streetly, Matthew J. Laubach, Jacob Richardson, Paul Schey, Stephen A. BE Schey, SA Yong, KL Marcus, R Anderson, KC TI Treatment of relapsed/refractory myeloma SO MYELOMA: PATHOLOGY, DIAGNOSIS, AND TREATMENT LA English DT Article; Book Chapter ID REFRACTORY MULTIPLE-MYELOMA; STEM-CELL TRANSPLANTATION; PEGYLATED LIPOSOMAL DOXORUBICIN; LENALIDOMIDE PLUS DEXAMETHASONE; LOW-DOSE THALIDOMIDE; PROTEASOME INHIBITOR PS-341; PREVIOUSLY TREATED PATIENTS; SINGLE-AGENT THALIDOMIDE; PHASE-I TRIAL; COOPERATIVE-ONCOLOGY-GROUP C1 [Streetly, Matthew J.] Guys & St Thomas NHS Fdn Trust, Dept Haematol, London, England. [Laubach, Jacob; Richardson, Paul] Dana Faber Canc Inst, Hematol Malignancies Ctr, Boston, MA USA. [Schey, Stephen A.] Kings Coll London, Dept Haematol, London, England. [Schey, Stephen A.] Kings Coll Hosp NHS Fdn Trust, London, England. RP Streetly, MJ (reprint author), Guys & St Thomas NHS Fdn Trust, Dept Haematol, London, England. NR 182 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 978-1-107-01057-4 PY 2014 BP 144 EP 166 PG 23 WC Oncology; Hematology SC Oncology; Hematology GA BIB06 UT WOS:000327193500012 ER PT J AU Treon, SP Merlini, G AF Treon, Steven P. Merlini, Giampaolo BE Schey, SA Yong, KL Marcus, R Anderson, KC TI Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma SO MYELOMA: PATHOLOGY, DIAGNOSIS, AND TREATMENT LA English DT Article; Book Chapter ID CONSENSUS PANEL RECOMMENDATIONS; 2ND INTERNATIONAL WORKSHOP; IGM MONOCLONAL GAMMOPATHY; ANTIBODY-MEDIATED IMMUNOTHERAPY; COLD-REACTING AUTOANTIBODIES; COOPERATIVE-ONCOLOGY-GROUP; STEM-CELL TRANSPLANTATION; HIGH-DOSE THERAPY; PHASE-II TRIAL; PERIPHERAL NEUROPATHY C1 [Treon, Steven P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. [Merlini, Giampaolo] Univ Pavia, Dept Biochem, I-27100 Pavia, Italy. [Merlini, Giampaolo] Univ Hosp Policlin San Matteo, Biotechnol Res Labs, Pavia, Italy. RP Treon, SP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, 44 Binney St, Boston, MA 02115 USA. NR 192 TC 0 Z9 0 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-1-107-01057-4 PY 2014 BP 190 EP 215 PG 26 WC Oncology; Hematology SC Oncology; Hematology GA BIB06 UT WOS:000327193500015 ER PT B AU Anthony, RM AF Anthony, Robert M. BA Ackerman, ME Nimmerjahn, F BF Ackerman, ME Nimmerjahn, F TI Fc gamma Receptors as Therapeutic Targets SO ANTIBODY FC: LINKING ADAPTIVE AND INNATE IMMUNITY LA English DT Article; Book Chapter ID IDIOPATHIC THROMBOCYTOPENIC PURPURA; HELICOBACTER-PYLORI INFECTION; DEPENDENT CELLULAR CYTOTOXICITY; ANTI-CD20 MONOCLONAL-ANTIBODY; SYSTEMIC-LUPUS-ERYTHEMATOSUS; NON-HODGKINS-LYMPHOMA; IMMUNOGLOBULIN-G; IGG FC; ANTIINFLAMMATORY ACTIVITY; LINKED OLIGOSACCHARIDES C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA 02115 USA. RP Anthony, RM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA 02115 USA. NR 98 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-394818-2; 978-0-12-394802-1 PY 2014 BP 283 EP 296 PG 14 WC Immunology SC Immunology GA BHU43 UT WOS:000326685100016 ER PT J AU Yazinski, S Gomez, G AF Yazinski, Stepahnie Gomez, George TI Time Course of Structural and Functional Maturation of Human Olfactory Epithelial Cells In Vitro SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE neuronal cell culture; neurogenesis; intracellular calcium; odorant sensitivity; olfactory marker protein ID GENE DELETION CAUSES; ADULT HUMAN; SENSORY NEURONS; RECEPTOR-CELLS; SODIUM/CALCIUM EXCHANGER; ENSHEATHING CELLS; ODORANT DETECTION; CA2+ EXTRUSION; STEM-CELLS; NEUROGENESIS AB The unique ability of olfactory neurons to regenerate in vitro has allowed their use for the study of olfactory function, regeneration, and neurodegenerative disorders; thus, characterization of their properties is important. This present study attempts to establish the timeline of structural (protein expression) and functional (odorant sensitivity) maturation of human olfactory epithelial cells (hOE) in vitro using biopsy-derived cultured tissue. Cells were grown for 7 days; on each day, cells were tested for odorant sensitivity using calcium imaging techniques and then protein expression of each cell was tested using immunocytochemistry for proteins typically used for characterizing olfactory cells. Previous studies have shown that mature olfactory neurons in vitro attain a unique phase-bright morphology and express the olfactory marker protein (OMP). By day 3 in vitro, a variety of cells were odorant-sensitive, including both phase-bright and phase-dark cells that have previously been considered glial-like cells. The functional maturation of these hOEs appears to take place within 4 days. Interestingly, the emergence of an odorant sensitivity profile of both phase-bright and phase-dark cells preceded the expression of marker protein expression for OMP (which is expressed only by mature neurons in vivo). This structural maturation took 5 days, suggesting that the development of odorant sensitivity is not coincident with the expression of marker molecules that are hallmarks of structural maturation. These results have important implications for the use of hOEs as in vitro models of olfactory and neuronal function. (c) 2013 Wiley Periodicals, Inc. C1 [Yazinski, Stepahnie] Massachusetts Gen Hosp, Dept Med, Charlestown, MA USA. [Gomez, George] Univ Scranton, Dept Biol, Scranton, PA 18510 USA. RP Gomez, G (reprint author), Univ Scranton Biol LSC 395, 204 Monroe Ave, Scranton, PA 18510 USA. EM george.gomez@scranton.edu FU NIH/NIDCD [RO3DC004954-01A2] FX Contract grant sponsor: NIH/NIDCD; Contract grant number: RO3DC004954-01A2. NR 45 TC 0 Z9 0 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0360-4012 EI 1097-4547 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JAN PY 2014 VL 92 IS 1 BP 64 EP 73 DI 10.1002/jnr.23296 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 254LK UT WOS:000327167000007 PM 24123277 ER PT J AU Treon, SP Merlini, G AF Treon, Steven P. Merlini, Giampaolo BE Marcus, R Sweetenham, JW Williams, ME TI Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma SO LYMPHOMA: PATHOLOGY, DIAGNOSIS, AND TREATMENT, 2ND EDITION LA English DT Article; Book Chapter ID CONSENSUS PANEL RECOMMENDATIONS; 2ND INTERNATIONAL WORKSHOP; PHASE-II TRIAL; PROGNOSTIC-FACTORS; SOMATIC MUTATION; MONOCLONAL GAMMOPATHIES; RITUXIMAB THERAPY; SCORING SYSTEM; CLINICAL-TRIAL; 6Q DELETION C1 [Treon, Steven P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. [Merlini, Giampaolo] Univ Pavia, Dept Biochem, I-27100 Pavia, Italy. [Merlini, Giampaolo] Univ Hosp Policlin San Matteo, Biotechnol Res Labs, Pavia, Italy. RP Treon, SP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, 44 Binney St, Boston, MA 02115 USA. NR 85 TC 0 Z9 0 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-1-107-01059-8 PY 2014 BP 138 EP 154 PG 17 WC Oncology; Hematology SC Oncology; Hematology GA BIA08 UT WOS:000327127000011 ER PT J AU Davids, MS Brown, JR AF Davids, Matthew S. Brown, Jennifer R. BE Marcus, R Sweetenham, JW Williams, ME TI Atypical lymphoproliferative, histiocytic, and dendritic cell disorders SO LYMPHOMA: PATHOLOGY, DIAGNOSIS, AND TREATMENT, 2ND EDITION LA English DT Article; Book Chapter ID MULTICENTRIC CASTLEMANS-DISEASE; ROSAI-DORFMAN-DISEASE; LYMPH-NODE HYPERPLASIA; HUMAN-IMMUNODEFICIENCY-VIRUS; ERDHEIM-CHESTER-DISEASE; MASSIVE LYMPHADENOPATHY; LYMPHOMATOID GRANULOMATOSIS; SINUS HISTIOCYTOSIS; KAPOSIS-SARCOMA; HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS C1 [Davids, Matthew S.; Brown, Jennifer R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Davids, MS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 69 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 978-1-107-01059-8 PY 2014 BP 286 EP 298 PG 13 WC Oncology; Hematology SC Oncology; Hematology GA BIA08 UT WOS:000327127000019 ER PT J AU Green, DM Nolan, VG Goodman, PJ Whitton, JA Srivastava, D Leisenring, WM Neglia, JP Sklar, CA Kaste, SC Hudson, MM Diller, LR Stovall, M Donaldson, SS Robison, LL AF Green, Daniel M. Nolan, Vikki G. Goodman, Pamela J. Whitton, John A. Srivastava, DeoKumar Leisenring, Wendy M. Neglia, Joseph P. Sklar, Charles A. Kaste, Sue C. Hudson, Melissa M. Diller, Lisa R. Stovall, Marilyn Donaldson, Sarah S. Robison, Leslie L. TI The Cyclophosphamide Equivalent Dose as an Approach for Quantifying Alkylating Agent Exposure: A Report From the Childhood Cancer Survivor Study SO PEDIATRIC BLOOD & CANCER LA English DT Article DE alkylating agent; Alkylating Agent Dose score; chemotherapy; cyclophosphamide; late effects of cancer treatment; long-term survival ID ADVANCED HODGKINS-DISEASE; PROSPECTIVE RANDOMIZED-TRIAL; 2ND MALIGNANT NEOPLASMS; LEUKEMIA-GROUP-B; COMBINATION CHEMOTHERAPY; 5-YEAR SURVIVORS; ONCOLOGY-GROUP; PROMACE-MOPP; PROCARBAZINE; PREDNISONE AB BackgroundEstimation of the risk of adverse long-term outcomes such as second malignant neoplasms and infertility often requires reproducible quantification of exposures. The method for quantification should be easily utilized and valid across different study populations. The widely used Alkylating Agent Dose (AAD) score is derived from the drug dose distribution of the study population and thus cannot be used for comparisons across populations as each will have a unique distribution of drug doses. MethodsWe compared the performance of the Cyclophosphamide Equivalent Dose (CED), a unit for quantifying alkylating agent exposure independent of study population, to the AAD. Comparisons included associations from three Childhood Cancer Survivor Study (CCSS) outcome analyses, receiver operator characteristic (ROC) curves and goodness of fit based on the Akaike's Information Criterion (AIC). ResultsThe CED and AAD performed essentially identically in analyses of risk for pregnancy among the partners of male CCSS participants, risk for adverse dental outcomes among all CCSS participants and risk for premature menopause among female CCSS participants, based on similar associations, lack of statistically significant differences between the areas under the ROC curves and similar model fit values for the AIC between models including the two measures of exposure. ConclusionThe CED is easily calculated, facilitating its use for patient counseling. It is independent of the drug dose distribution of a particular patient population, a characteristic that will allow direct comparisons of outcomes among epidemiological cohorts. We recommend the use of the CED in future research assessing cumulative alkylating agent exposure. Pediatr Blood Cancer 2014;61:53-67. (c) 2013 Wiley Periodicals, Inc. C1 [Green, Daniel M.; Hudson, Melissa M.; Robison, Leslie L.] St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA. [Nolan, Vikki G.] Univ Memphis, Dept Epidemiol & Biostat, Memphis, TN 38152 USA. [Goodman, Pamela J.; Whitton, John A.; Leisenring, Wendy M.] Fred Hutchinson Canc Res Ctr, Clin Stat Program, Seattle, WA 98104 USA. [Goodman, Pamela J.; Whitton, John A.; Leisenring, Wendy M.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. [Srivastava, DeoKumar] St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38105 USA. [Neglia, Joseph P.] Univ Minnesota, Sch Med, Dept Pediat, Minneapolis, MN 55455 USA. [Sklar, Charles A.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. [Kaste, Sue C.] St Jude Childrens Res Hosp, Dept Radiol Sci, Memphis, TN 38105 USA. [Kaste, Sue C.; Hudson, Melissa M.] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA. [Kaste, Sue C.] Univ Tennessee, Sch Hlth Sci, Dept Radiol, Memphis, TN USA. [Diller, Lisa R.] Dana Farber Canc Ctr, Dept Pediat Oncol, Boston, MA USA. [Stovall, Marilyn] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. [Donaldson, Sarah S.] Stanford Univ, Med Ctr, Dept Radiat Oncol, Stanford, CA 94305 USA. RP Green, DM (reprint author), St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, 262 Danny Thomas Pl,Mail Stop 735, Memphis, TN 38105 USA. EM daniel.green@stjude.org FU United States Public Health Service [CA-55727, CA-21765]; St. Jude Children's Research Hospital by the American Lebanese Syrian Associated Charities (ALSAC) FX Grant sponsor: United States Public Health Service; Grant numbers: CA-55727; CA-21765; Grant sponsor: St. Jude Children's Research Hospital by the American Lebanese Syrian Associated Charities (ALSAC) NR 52 TC 31 Z9 31 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JAN PY 2014 VL 61 IS 1 BP 53 EP 67 DI 10.1002/pbc.24679 PG 15 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 249GG UT WOS:000326765100011 PM 23940101 ER PT J AU Hebert, EA Dugas, MJ Tulloch, TG Holowka, DW AF Hebert, Elizabeth A. Dugas, Michel J. Tulloch, Tyler G. Holowka, Darren W. TI Positive beliefs about worry: A psychometric evaluation of the Why Worry-II SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article DE Generalized anxiety disorder; Worry; Positive beliefs about worry; Confirmatory factor analysis; Psychometrics ID GENERALIZED ANXIETY DISORDER; COGNITIVE MODEL; QUESTIONNAIRE; INVENTORY AB Positive beliefs about worry are theorized to maintain excessive and uncontrollable worry, the hallmark of generalized anxiety disorder (GAD; American Psychiatric Association, 2013). The Why Worry-II (WW-II) is a 25-item revised questionnaire designed to measure five positive beliefs about worry. These five beliefs are that worry: (1) facilitates problem solving; (2) enhances motivation; (3) protects against negative emotions; (4) prevents negative outcomes; and (5) reflects a positive personality trait. The main goal of this study was to assess the WW-II's psychometric properties, including its factor structure. Undergraduate participants (N = 309) completed the WW-II, and measures of worry, depression, anxiety, and positive and negative beliefs about worry. Overall, the results suggest that the five-factor model is a good fit to the data. The WW-II demonstrated excellent internal consistency, good test-retest reliability at six weeks, and evidence of convergent and divergent validity. The WW-II also uniquely predicted worry severity. Overall, our findings suggest that the WW-II has a five-factor structure congruent with theoretical predictions, sound psychometric properties, and a unique relationship to excessive worry. The theoretical and clinical implications of these findings are discussed. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Hebert, Elizabeth A.; Dugas, Michel J.] Concordia Univ, Dept Psychol, Montreal, PQ, Canada. [Dugas, Michel J.] Hop Sacre Coeur Montreal, Clin Troubles Anxieux, Montreal, PQ, Canada. [Tulloch, Tyler G.] Ryerson Univ, Dept Psychol, Toronto, ON, Canada. [Holowka, Darren W.] US Dept Vet Affairs, Natl Ctr PTSD, Washington, DC USA. [Holowka, Darren W.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. RP Dugas, MJ (reprint author), Univ Quebec Outaouais, Dept Psychoeduc & Psychol, POB 1250,Stn Hull, Gatineau, PQ J8X 3X7, Canada. EM michel.dugas@uqo.ca OI Dugas, Michel/0000-0003-2615-1782 NR 29 TC 4 Z9 4 U1 1 U2 21 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0191-8869 J9 PERS INDIV DIFFER JI Pers. Individ. Differ. PD JAN PY 2014 VL 56 BP 3 EP 8 DI 10.1016/j.paid.2013.08.009 PG 6 WC Psychology, Social SC Psychology GA 244VV UT WOS:000326419200001 ER PT S AU Kolodziej, AF Zhang, ZD Overoye-Chan, K Jacques, V Caravan, P AF Kolodziej, Andrew F. Zhang, Zhaoda Overoye-Chan, Kirsten Jacques, Vincent Caravan, Peter BE Nixon, AE TI Peptide Optimization and Conjugation Strategies in the Development of Molecularly Targeted Magnetic Resonance Imaging Contrast Agents SO THERAPEUTIC PEPTIDES: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Magnetic resonance imaging; Targeted contrast agent; Peptide conjugation; Peptide optimization ID PHAGE DISPLAY; SOLID-PHASE; GADOLINIUM; ULTRASOUND; CHEMISTRY; LIBRARIES; THROMBUS; EP-2104R; DELIVERY; ACID AB Peptides are highly selective, high-affinity ligands for a diverse array of disease targets, but suitably derivatizing them for application as diagnostic or therapeutic agents often presents a significant challenge. Covalent modification with metal chelates frequently results in decreased binding affinity, so a variety of strategies must be explored to find suitable locations for modification and facile peptide conjugation chemistries that maintain or enhance binding affinity. In this chapter, we present a paradigm for systematically optimizing peptide binding and determining the favorable sites and methods for peptide conjugation. This strategy is illustrated by two case studies of peptide-based targeted gadolinium contrast agents: EP-2104R for diagnosis of thrombosis and EP-3533 for diagnosis of cardiac perfusion and fibrosis. Two different architectures for the peptide-metal complex conjugation were designed: EP-2104R contains a total of four gadolinium (Gd) chelates linked at the N- and C-termini, whereas EP-3533 is derivatized with three Gd chelates, two on the N-terminus and one on a lysine side chain. Detailed protocols are provided for two Gd chelate conjugation methods. C1 [Kolodziej, Andrew F.; Zhang, Zhaoda; Overoye-Chan, Kirsten; Jacques, Vincent] EPIX Pharmaceut, Lexington, MA USA. [Caravan, Peter] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Caravan, Peter] Harvard Univ, Sch Med, Charlestown, MA USA. RP Kolodziej, AF (reprint author), EPIX Pharmaceut, Lexington, MA USA. NR 34 TC 8 Z9 8 U1 1 U2 14 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-62703-673-3; 978-1-62703-672-6 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2014 VL 1088 BP 185 EP 211 DI 10.1007/978-1-62703-673-3_13 D2 10.1007/978-1-62703-673-3 PG 27 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA BHR83 UT WOS:000326509500014 PM 24146405 ER PT B AU Pillion, JP Santos, F Vernick, DM Shapiro, J AF Pillion, Joseph P. Santos, Felipe Vernick, David M. Shapiro, Jay BE Shapiro, JR TI Hearing Loss in Osteogenesis Imperfecta SO OSTEOGENESIS IMPERFECTA: A TRANSLATIONAL APPROACH TO BRITTLE BONE DISEASE LA English DT Article; Book Chapter ID TEMPORAL BONE; COCHLEAR IMPLANTATION; AUDIOLOGICAL PHENOTYPE; OTOSCLEROSIS; MUTATIONS; CHILDREN; TERM; ASSOCIATION; STAPEDOTOMY; DENSITY C1 [Pillion, Joseph P.; Shapiro, Jay] Kennedy Krieger Inst, Dept Audiol, Baltimore, MD USA. [Shapiro, Jay] Kennedy Krieger Inst, Johns Hopkins Sch Med, Bone & Osteogenesis Imperfecta Dept, Baltimore, MD USA. [Shapiro, Jay] Kennedy Krieger Inst, Johns Hopkins Sch Med, Dept Phys Med & Rehabil, Baltimore, MD USA. [Pillion, Joseph P.; Shapiro, Jay] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Santos, Felipe] Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. [Vernick, David M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Pillion, JP (reprint author), Kennedy Krieger Inst, Dept Audiol, Baltimore, MD USA. NR 58 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-397789-2; 978-0-12-397165-4 PY 2014 BP 305 EP 312 DI 10.1016/B978-0-12-397165-4.00032-0 PG 8 WC Orthopedics SC Orthopedics GA BHP54 UT WOS:000326245700034 ER PT B AU McNamee, S AF McNamee, Shane BE Murphy, D TI History of Amputation: From the Past to the Present SO FUNDAMENTALS OF AMPUTATION CARE AND PROSTHETICS LA English DT Article; Book Chapter C1 [McNamee, Shane] US Dept Vet Affairs, Hunter Holmes McGuire VA Med Ctr, Dept Phys Med & Rehabil, Richmond, VA USA. [McNamee, Shane] Virginia Commonwealth Univ, Dept Phys Med & Rehabil, Richmond, VA USA. RP McNamee, S (reprint author), US Dept Vet Affairs, Hunter Holmes McGuire VA Med Ctr, Dept Phys Med & Rehabil, Richmond, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-9362-8770-3 PY 2014 BP 1 EP 6 PG 6 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA BGT29 UT WOS:000324075500001 ER PT B AU McNamee, S AF McNamee, Shane BE Murphy, D TI Physical Exam SO FUNDAMENTALS OF AMPUTATION CARE AND PROSTHETICS LA English DT Article; Book Chapter C1 [McNamee, Shane] US Dept Vet Affairs, Hunter Holmes McGuire VA Med Ctr, Dept Phys Med & Rehabil, Richmond, VA USA. [McNamee, Shane] Virginia Commonwealth Univ, Dept Phys Med & Rehabil, Richmond, VA USA. RP McNamee, S (reprint author), US Dept Vet Affairs, Hunter Holmes McGuire VA Med Ctr, Dept Phys Med & Rehabil, Richmond, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-9362-8770-3 PY 2014 BP 7 EP 14 PG 8 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA BGT29 UT WOS:000324075500002 ER PT J AU Olsen, LR Kudahl, UJ Simon, C Sun, J Schonbach, C Reinherz, EL Zhang, GL Brusic, V AF Olsen, Lars Ronn Kudahl, Ulrich Johan Simon, Christian Sun, Jing Schoenbach, Christian Reinherz, Ellis L. Zhang, Guang Lan Brusic, Vladimir TI BlockLogo: Visualization of peptide and sequence motif conservation SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE T-cell epitope; B-cell epitope; Protein-protein interaction; Block entropy; Sequence variability and conservation ID BINDING PREDICTION SERVERS; MHC CLASS-II; CONSENSUS SEQUENCES; VACCINE RESEARCH; LOGOS; TOOL; RNA; ALIGNMENTS; REPRESENTATION; PROTEINS AB BlockLogo is a web-server application for the visualization of protein and nucleotide fragments, continuous protein sequence motifs, and discontinuous sequence motifs using calculation of block entropy from multiple sequence alignments. The user input consists of a multiple sequence alignment, selection of motif positions, type of sequence, and output format definition. The output has BlockLogo along with the sequence logo, and a table of motif frequencies. We deployed BlockLogo as an online application and have demonstrated its utility through examples that show visualization of T-cell epitopes and B-cell epitopes (both continuous and discontinuous). Our additional example shows a visualization and analysis of structural motifs that determine the specificity of peptide binding to HLA-DR molecules. The BlockLogo server also employs selected experimentally validated prediction algorithms to enable on-the-fly prediction of MHC binding affinity to 15 common HLA class land class II alleles as well as visual analysis of discontinuous epitopes from multiple sequence alignments. It enables the visualization and analysis of structural and functional motifs that are usually described as regular expressions. It provides a compact view of discontinuous motifs composed of distant positions within biological sequences. BlockLogo is available at: http://research4.dfci.harvard.edu/cvc/blocklogo/ and http://met-hilab.bu.edu/blocklogo/. (C) 2013 Elsevier B.V. All rights reserved. C1 [Olsen, Lars Ronn; Kudahl, Ulrich Johan; Simon, Christian; Sun, Jing; Reinherz, Ellis L.; Zhang, Guang Lan; Brusic, Vladimir] Harvard Univ, Sch Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Olsen, Lars Ronn] Univ Copenhagen, Bioinformat Ctr, Dept Biol, Copenhagen, Denmark. [Kudahl, Ulrich Johan; Simon, Christian] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Sun, Jing; Reinherz, Ellis L.; Zhang, Guang Lan; Brusic, Vladimir] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Schoenbach, Christian] Kyushu Inst Technol, Grad Sch Comp Sci & Syst Engn, Dept Biosci & Bioinformat, Fukuoka, Japan. [Schoenbach, Christian] Nazarbayev Univ, Sch Sci & Technol, Dept Biol & Chem, Astana 010000, Kazakhstan. [Reinherz, Ellis L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. [Reinherz, Ellis L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Zhang, Guang Lan; Brusic, Vladimir] Boston Univ, Dept Comp Sci, Metropolitan Coll, Boston, MA 02215 USA. RP Brusic, V (reprint author), Dana Farber Canc Inst, Canc Vaccine Ctr, HIM 418,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM vladimir_brusic@dfci.harvard.edu RI Schonbach, Christian/B-1998-2009; OI Schonbach, Christian/0000-0002-0693-7617; Olsen, Lars Ronn/0000-0002-6725-7850; Simon, Christian/0000-0002-5866-5967 FU Novo Nordisk Foundation; Oticon Foundation; Novo Scholarship Programme; NIH [U01 AI 90043] FX LRO was funded by the Novo Nordisk Foundation; UJK was funded by the Oticon Foundation; C. Simon was funded by the Novo Scholarship Programme; and GLZ, JS, VB, and ELR acknowledge funding from NIH grant U01 AI 90043. NR 35 TC 9 Z9 9 U1 0 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 EI 1872-7905 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD DEC 31 PY 2013 VL 400 SI SI BP 37 EP 44 DI 10.1016/j.jim.2013.08.014 PG 8 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 287JS UT WOS:000329538700006 PM 24001880 ER PT J AU Li, WY Sun, S Chen, Y Yu, HQ Chen, ZY Li, HW AF Li, Wenyan Sun, Shan Chen, Yan Yu, Huiqian Chen, Zheng-Yi Li, Huawei TI Disrupting the Interaction between Retinoblastoma Protein and Raf-1 Leads to Defects in Progenitor Cell Proliferation and Survival during Early Inner Ear Development SO PLOS ONE LA English DT Article ID RB-RAF-1 INTERACTION; SENSORY EPITHELIA; POCKET PROTEINS; CYCLE CONTROL; HAIR-CELLS; STEM-CELLS; IN-VIVO; CANCER; ANGIOGENESIS; INACTIVATION AB The retinoblastoma protein (pRb) is required for cell-cycle exit of embryonic mammalian hair cells but is not required for hair cell fate determination and early differentiation, and this provides a strategy for hair cell regeneration by manipulating the pRb pathway. To reveal the mechanism of pRb functional modification in the inner ear, we compared the effects of attenuated pRb phosphorylation by an inhibitor of the Mitogen-Activated Protein (MAP) kinase pathway and an inhibitor of the Rb-Raf-1 interaction on cultured chicken otocysts. We demonstrated that the activity of pRb is correlated with its phosphorylation state, which is regulated by a newly established cell cycle-independent pathway mediated by the physical interaction between Raf-1 and pRb. The phosphorylation of pRb plays an important role during the early stage of inner ear development, and attenuated phosphorylation in progenitor cells leads to cell cycle arrest and increased apoptosis along with a global down-regulation of the genes involved in cell cycle progression. Our study provides novel routes to modulate pRb function for hair cell regeneration. C1 [Li, Wenyan; Yu, Huiqian] Fudan Univ, Dept Otorhinolaryngol, Affiliated Eye & ENT Hosp, Shanghai 200433, Peoples R China. [Sun, Shan; Chen, Yan] Fudan Univ, Res Ctr, Affiliated Eye & ENT Hosp, Shanghai 200433, Peoples R China. [Li, Huawei] Fudan Univ, Inst Stem Cell & Regenerat Med, Inst Biomed Sci, Shanghai 200433, Peoples R China. [Li, Huawei] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. [Li, Wenyan; Chen, Zheng-Yi] Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02115 USA. [Li, Wenyan; Chen, Zheng-Yi] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Li, Wenyan; Chen, Zheng-Yi] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Li, HW (reprint author), Fudan Univ, Inst Stem Cell & Regenerat Med, Inst Biomed Sci, Shanghai 200433, Peoples R China. EM lihuawei63@gmail.com FU Major State Basic Research Development Program of China (973 Program) [2011CB504506, 2010CB945503]; National Natural Science Foundation of China [81230019, 81070793, 30901668]; Program for Changjiang Scholars and Innovative Research Team in Universities [IRT1010]; Medical Guiding Fund of the Science and Technology Commission of Shanghai Municipality [10411962100]; Program of Outstanding Shanghai Academic Leaders [11XD1401300]; Specialized Research Fund for the Doctor Program of Higher Education [20120071110077]; Shanghai Rising-Star Program [12QA1400500]; Program of Leading Medical Personnel in Shanghai FX This work was supported by grants from the Major State Basic Research Development Program of China (973 Program) (2011CB504506, 2010CB945503), the National Natural Science Foundation of China (No. 81230019, 81070793, 30901668), the Program for Changjiang Scholars and Innovative Research Team in Universities (IRT1010), the Medical Guiding Fund of the Science and Technology Commission of Shanghai Municipality (10411962100), the Program of Outstanding Shanghai Academic Leaders (11XD1401300), the Specialized Research Fund for the Doctor Program of Higher Education (20120071110077), the Shanghai Rising-Star Program (12QA1400500) and the Program of Leading Medical Personnel in Shanghai. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 TC 4 Z9 4 U1 1 U2 14 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 2013 VL 8 IS 12 AR e83726 DI 10.1371/journal.pone.0083726 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 284NF UT WOS:000329325200112 PM 24391814 ER PT J AU Wong, EB Akilimali, NA Govender, P Sullivan, ZA Cosgrove, C Pillay, M Lewinsohn, DM Bishai, WR Walker, BD Ndung'u, T Klenerman, P Kasprowicz, VO AF Wong, Emily B. Akilimali, Ngomu Akeem Govender, Pamla Sullivan, Zuri A. Cosgrove, Cormac Pillay, Mona Lewinsohn, David M. Bishai, William R. Walker, Bruce D. Ndung'u, Thumbi Klenerman, Paul Kasprowicz, Victoria O. TI Low Levels of Peripheral CD161++CD8+Mucosal Associated Invariant T (MAIT) Cells Are Found in HIV and HIV/TB Co-Infection SO PLOS ONE LA English DT Article ID TUBERCULOSIS CHALLENGE; CD161 EXPRESSION; VIRUS-INFECTION; POPULATION; ACTIVATION; RESPONSES; PATHWAY; DISEASE; DEFINES; HEALTH AB Background: High expression of CD161 on CD8+ T cells is associated with a population of cells thought to play a role in mucosal immunity. We wished to investigate this subset in an HIV and Mycobacterium tuberculosis (MTB) endemic African setting. Methods: A flow cytometric approach was used to assess the frequency and phenotype of CD161++CD8+ T cells. 80 individuals were recruited for cross-sectional analysis: controls (n = 18), latent MTB infection (LTBI) only (n = 16), pulmonary tuberculosis (TB) only (n = 8), HIV only (n = 13), HIV and LTBI co-infection (n = 15) and HIV and TB co-infection (n = 10). The impact of acute HIV infection was assessed in 5 individuals recruited within 3 weeks of infection. The frequency of CD161++CD8+ T cells was assessed prior to and during antiretroviral therapy (ART) in 14 HIV-positive patients. Results: CD161++CD8+ T cells expressed high levels of the HIV co-receptor CCR5, the tissue-homing marker CCR6, and the Mucosal-Associated Invariant T (MAIT) cell TCR V alpha 7.2. Acute and chronic HIV were associated with lower frequencies of CD161++CD8+ T cells, which did not correlate with CD4 count or HIV viral load. ART was not associated with an increase in CD161++CD8+ T cell frequency. There was a trend towards lower levels of CD161++CD8+ T cells in HIV-negative individuals with active and latent TB. In those co-infected with HIV and TB, CD161++CD8+T cells were found at low levels similar to those seen in HIV mono-infection. Conclusions: The frequencies and phenotype of CD161++CD8+ T cells in this South African cohort are comparable to those published in European and US cohorts. Low-levels of this population were associated with acute and chronic HIV infection. Lower levels of the tissue-trophic CD161++CD8+ T cell population may contribute to weakened mucosal immune defense, making HIV-infected subjects more susceptible to pulmonary and gastrointestinal infections and detrimentally impacting on host defense against TB. C1 [Wong, Emily B.; Akilimali, Ngomu Akeem; Govender, Pamla; Sullivan, Zuri A.; Bishai, William R.; Ndung'u, Thumbi; Kasprowicz, Victoria O.] KwaZulu Natal Res Inst TB & HIV, Durban, South Africa. [Wong, Emily B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Akilimali, Ngomu Akeem; Govender, Pamla; Pillay, Mona; Walker, Bruce D.; Ndung'u, Thumbi; Kasprowicz, Victoria O.] Univ KwaZulu Natal, HIV Pathogenesis Programme, Durban, South Africa. [Sullivan, Zuri A.; Bishai, William R.] Johns Hopkins Sch Med, Div Infect Dis, Baltimore, MD USA. [Cosgrove, Cormac; Klenerman, Paul] Univ Oxford, Oxford, England. [Lewinsohn, David M.] Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland, OR 97201 USA. [Lewinsohn, David M.] Portland VA Med Ctr, Portland, OR USA. [Walker, Bruce D.; Ndung'u, Thumbi; Kasprowicz, Victoria O.] Harvard Univ, Sch Med, Ragon Inst MGH Massachusetts Inst Technol & Harva, Cambridge, MA 02138 USA. [Ndung'u, Thumbi] Max Planck Inst Infekt Biol, D-10117 Berlin, Germany. RP Wong, EB (reprint author), KwaZulu Natal Res Inst TB & HIV, Durban, South Africa. EM emilybethwong@gmail.com RI Lewinsohn, David/I-4936-2013; OI Lewinsohn, David/0000-0001-9906-9494; Ndung'u, Thumbi/0000-0003-2962-3992 FU Howard Hughes Medical Institute (HHMI); KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH); Harvard University CFAR [P30 AI060354]; NIH [AI 097138, AI 007387]; Wellcome Trust [WT019663MA]; Oxford Martin School; NIAID U19 Bio-defense Program [NIH NIAID 1U19AI082630-01]; NIHR Biomedical Research Centre, Oxford FX The authors would like to thank the following funders: the Howard Hughes Medical Institute (HHMI), the KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), the Harvard University CFAR grant (P30 AI060354), the NIH (grant AI 097138 and AI 007387), the Wellcome Trust (WT019663MA), the Oxford Martin School, the NIAID U19 Bio-defense Program (NIH NIAID 1U19AI082630-01), and the NIHR Biomedical Research Centre, Oxford. PK is an NIHR Senior Investigator. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 33 TC 28 Z9 28 U1 6 U2 21 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 2013 VL 8 IS 12 AR e83474 DI 10.1371/journal.pone.0083474 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 284NF UT WOS:000329325200070 PM 24391773 ER PT J AU Nag, A Savova, V Fung, HL Miron, A Yuan, GC Zhang, K Gimelbrant, AA AF Nag, Anwesha Savova, Virginia Fung, Ho-Lim Miron, Alexander Yuan, Guo-Cheng Zhang, Kun Gimelbrant, Alexander A. TI Chromatin signature of widespread monoallelic expression SO ELIFE LA English DT Article ID HUMAN GENOME; GENE-EXPRESSION; READ ALIGNMENT; IMPRINTED GENE; BREAST-CANCER; STEM-CELLS; CHROMOSOME; DATABASE; MOUSE; STATE AB In mammals, numerous autosomal genes are subject to mitotically stable monoallelic expression (MAE), including genes that play critical roles in a variety of human diseases. Due to challenges posed by the clonal nature of MAE, very little is known about its regulation; in particular, no molecular features have been specifically linked to MAE. In this study, we report an approach that distinguishes MAE genes in human cells with great accuracy: a chromatin signature consisting of chromatin marks associated with active transcription (H3K36me3) and silencing (H3K27me3) simultaneously occurring in the gene body. The MAE signature is present in similar to 20% of ubiquitously expressed genes and over 30% of tissue-specific genes across cell types. Notably, it is enriched among key developmental genes that have bivalent chromatin structure in pluripotent cells. Our results open a new approach to the study of MAE that is independent of polymorphisms, and suggest that MAE is linked to cell differentiation. C1 [Nag, Anwesha; Savova, Virginia; Miron, Alexander; Gimelbrant, Alexander A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Nag, Anwesha; Savova, Virginia; Gimelbrant, Alexander A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Fung, Ho-Lim; Zhang, Kun] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. [Yuan, Guo-Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Gimelbrant, AA (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM alexander_gimelbrant@dfci.harvard.edu FU Claudia Adams Barr Foundation; Susan F Smith Center for Women's Cancers; National Institutes of Health [R01GM097253]; Pew Scholars Program FX Claudia Adams Barr Foundation Alexander A Gimelbrant; Susan F Smith Center for Women's Cancers Alexander A Gimelbrant; National Institutes of Health R01GM097253 Kun Zhang; Pew Scholars Program Alexander A Gimelbrant NR 55 TC 24 Z9 24 U1 0 U2 7 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD DEC 31 PY 2013 VL 2 AR e01256 DI 10.7554/eLife.01256 PG 19 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 282ME UT WOS:000329175100003 PM 24381246 ER PT J AU Kim, B Kang, ES Fava, M Mischoulon, D Soskin, D Yu, BH Lee, D Lee, DY Park, HD Jeon, HJ AF Kim, Bora Kang, Eun-Suk Fava, Maurizio Mischoulon, David Soskin, David Yu, Bum-Hee Lee, Dongsoo Lee, Dong-Yun Park, Hyung-Doo Jeon, Hong Jin TI Follicle-stimulating hormone (FSH), current suicidal ideation and attempt in female patients with major depressive disorder SO PSYCHIATRY RESEARCH LA English DT Article DE Major depressive disorder; Suicide; FSH; Hormone ID PITUITARY-GONADAL AXIS; ANTIDEPRESSANT TREATMENTS; SEROTONIN TRANSPORTER; POSTMENOPAUSAL WOMEN; MENTAL-DISORDERS; SEX-DIFFERENCES; RISK-FACTORS; ESTRADIOL; BEHAVIOR; PREMENOPAUSAL AB Current suicidal ideation and attempts are more commonly found in female patients with major depressive disorder (MDD) than in males. However, little is known about the relationship between activity of female reproductive hormones and suicide. The study population consisted of 490 female MDD patients of age >= 18. They were assessed by the Mini-International Neuropsychiatric Interview. At the same visit, we measured blood Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), estradiol, progesterone, Adrenocorticotropic Hormone (ACTH), cortisol, thyroid hormones, and prolactin. Blood FSH showed a significant difference among female MDD patients with suicide attempt, those with ideation, and those without within the previous month. Post-hoc analysis also showed that FSH was significantly lower in MDD patients with suicide attempt and ideation than those without, whereas other hormones showed no differences between those with and without attempt. FSH was negatively associated with current suicidality scores after adjustment for age and education years in all age groups. FSH was significantly lower in those with current suicide ideation or attempt than those without in age 45 years or under, but not in other age groups. In conclusion, blood FSH is significantly lower in female MOD patients with current suicide attempt or ideation than those without, especially in age 45 years or under. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Kim, Bora; Yu, Bum-Hee; Lee, Dongsoo; Jeon, Hong Jin] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Psychiat,Depress Ctr, Seoul 135710, South Korea. [Kang, Eun-Suk; Park, Hyung-Doo] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Lab Med, Seoul 135710, South Korea. [Fava, Maurizio; Mischoulon, David; Soskin, David; Jeon, Hong Jin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. [Lee, Dong-Yun] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Obstet & Gynecol, Seoul 135710, South Korea. RP Jeon, HJ (reprint author), Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Psychiat,Depress Ctr, 50 Irwon Dong, Seoul 135710, South Korea. EM jeonhj@skku.edu FU National Research Foundation of Korea (NRF); Ministry of Education, Science and Technology [2011-0013064]; Samsung Biomedical Research Institute [C-B1-311] FX This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (No. 2011-0013064). This research was also supported by the Samsung Biomedical Research Institute Grant (SBRI) (C-B1-311). NR 48 TC 8 Z9 8 U1 4 U2 21 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 2013 VL 210 IS 3 BP 951 EP 956 DI 10.1016/j.psychres.2013.08.057 PG 6 WC Psychiatry SC Psychiatry GA 285TI UT WOS:000329417500045 PM 24080256 ER PT J AU Hartmann, AS Thomas, JJ Wilson, AC Wilhelm, S AF Hartmann, Andrea S. Thomas, Jennifer J. Wilson, Anne C. Wilhelm, Sabine TI Insight impairment in body image disorders: Delusionality and overvalued ideas in anorexia nervosa versus body dysmorphic disorder SO PSYCHIATRY RESEARCH LA English DT Article DE Insight; Delusionality; Ideas/delusions of reference; Overvalued ideas; Anorexia nervosa; Body dysmorphic disorder ID OBSESSIVE-COMPULSIVE DISORDER; EATING-DISORDERS; CLINICAL-FEATURES; DOUBLE-BLIND; DSM-V; OLANZAPINE; PLACEBO; RELIABILITY; AUGMENTATION; BELIEFS AB The two body image disorders anorexia nervosa (AN) and body dysmorphic disorder (BDD) share many similarities. Delusionality in BDD has recently gained increased attention, as the new DSM-5 criteria for BDD include an insight specifier. However, delusionalilty in AN has rarely been examined. We evaluated the delusionality of appearance-related beliefs in AN (n=19) vs. BDD (n=22) via structured interview. Participants also completed measures of disorder-specific psychopathology and body image. Compared to those with AN, individuals with BDD exhibited significantly greater delusionality on a dimensional scale (p=0.0014, d=1.07), and were more likely to meet dichotomous criteria for delusional beliefs (p=0.021, V=0.36). In AN, delusionality was associated specifically with shape concerns and drive for thinness; in BDD, delusionality was related to the severity of BDD symptoms (all p <0.05). Delusionality of appearance beliefs is present in individuals with AN, but is less pronounced than in BDD. Nevertheless, as high delusionality might predict poor treatment outcome in AN, treatment strategies that were originally developed to address delusionality in BDD might be modified for AN. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Hartmann, Andrea S.] Univ Osnabruck, Dept Human Sci, Inst Psychol, D-49069 Osnabruck, Germany. [Hartmann, Andrea S.; Thomas, Jennifer J.; Wilson, Anne C.; Wilhelm, Sabine] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Hartmann, Andrea S.; Thomas, Jennifer J.; Wilson, Anne C.; Wilhelm, Sabine] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Hartmann, AS (reprint author), Univ Osnabruck, Dept Human Sci, Inst Psychol, Knollstr 15, D-49069 Osnabruck, Germany. EM andrea.hartmann@uni-osnabrueck.de FU Swiss National Science Foundation [PBSKP1_134330/1, PBSKP1_140040]; Hilda and Preston Davis Foundation FX The present study was supported by a post-doctoral fellowship awarded to Andrea S. Hartmann by the Swiss National Science Foundation (PBSKP1_134330/1 and PBSKP1_140040), and a Hilda and Preston Davis Foundation grant to Jennifer J. Thomas and Kamryn T. Eddy. NR 63 TC 12 Z9 12 U1 4 U2 36 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 2013 VL 210 IS 3 BP 1129 EP 1135 DI 10.1016/j.psychres.2013.08.010 PG 7 WC Psychiatry SC Psychiatry GA 285TI UT WOS:000329417500071 PM 23992792 ER PT J AU McGuire, JF Nyirabahizi, E Kircanski, K Piacentini, J Peterson, AL Woods, DW Wilhelm, S Walkup, JT Scahill, L AF McGuire, Joseph F. Nyirabahizi, Epiphanie Kircanski, Katharina Piacentini, John Peterson, Alan L. Woods, Douglas W. Wilhelm, Sabine Walkup, John T. Scahill, Lawrence TI A cluster analysis of tic symptoms in children and adults with Tourette syndrome: Clinical correlates and treatment outcome SO PSYCHIATRY RESEARCH LA English DT Article DE Habit reversal training; Comprehensive behavioral intervention for tics; Tic symptom profiles; Chronic tic disorders; Treatment outcome; Cluster analysis ID OBSESSIVE COMPULSIVE SCALE; BEHAVIOR-THERAPY; FUNCTIONAL IMPAIRMENT; SEVERITY-SCALE; RELIABILITY; DISORDERS; PREVALENCE; VALIDITY; COMORBIDITY; PARENT AB Cluster analytic methods have examined the symptom presentation of chronic tic disorders (CTDs), with limited agreement across studies. The present study investigated patterns, clinical correlates, and treatment outcome of tic symptoms. 239 youth and adults with CTDs completed a battery of assessments at baseline to determine diagnoses, tic severity, and clinical characteristics. Participants were randomly assigned to receive either a comprehensive behavioral intervention for tics (CBIT) or psychoeducation and supportive therapy (PST). A cluster analysis was conducted on the baseline Yale Global Tic Severity Scale (YGTSS) symptom checklist to identify the constellations of tic symptoms. Four tic clusters were identified: Impulse Control and Complex Phonic Tics; Complex Motor Tics; Simple Head Motor/Vocal Tics; and Primarily Simple Motor Tics. Frequencies of tic symptoms showed few differences across youth and adults. Tic clusters had small associations with clinical characteristics and showed no associations to the presence of coexisting psychiatric conditions. Cluster membership scores did not predict treatment response to CBIT or tic severity reductions. Tic symptoms distinctly cluster with little difference across youth and adults, or coexisting conditions. This study, which is the first to examine tic clusters and response to treatment, suggested that tic symptom profiles respond equally well to CBIT. Clinical trials. gov. identifiers: NCT00218777; NCT00231985. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [McGuire, Joseph F.] Univ S Florida, Dept Psychol, Tampa, FL 33620 USA. [Nyirabahizi, Epiphanie] Yale Univ, Dept Epidemiol, New Haven, CT USA. [Nyirabahizi, Epiphanie] Yale Univ, Dept Publ Hlth, New Haven, CT USA. [Kircanski, Katharina] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. [Piacentini, John] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Peterson, Alan L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Woods, Douglas W.] Univ Wisconsin, Dept Psychol, Milwaukee, WI 53201 USA. [Wilhelm, Sabine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wilhelm, Sabine] Harvard Univ, Sch Med, Boston, MA USA. [Walkup, John T.] Cornell Univ, Weil Cornell Med Coll, Ithaca, NY USA. [Scahill, Lawrence] Emory Univ, Sch Med, Marcus Ctr, Atlanta, GA 30329 USA. RP Scahill, L (reprint author), Emory Univ, Sch Med, Marcus Ctr, 1920 Briarcliff Rd, Atlanta, GA 30329 USA. EM Lawrence.Scahill@emory.edu OI Scahill, Lawrence/0000-0001-5073-1707 FU NIMH from the National Institute of Mental Health [R01MH070802, 5R01MH069877, R01MH069874, RO1MH069875] FX This research was supported by NIMH Grants R01MH070802 (Dr. Piacentini), 5R01MH069877 (Dr. Wilhelm), R01MH069874 (Dr. Scahill), and RO1MH069875 (Dr. Petersen) from the National Institute of Mental Health with subcontracts to Drs. Piacentini and Woods. Dr. Walkup consulted on this grant. NR 39 TC 20 Z9 20 U1 4 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 2013 VL 210 IS 3 BP 1198 EP 1204 DI 10.1016/j.psychres.2013.09.021 PG 7 WC Psychiatry SC Psychiatry GA 285TI UT WOS:000329417500080 PM 24144615 ER PT J AU Storage, S Mandelkern, MA Phuong, J Kozman, M Neary, MK Brody, AL AF Storage, Steven Mandelkern, Mark A. Phuong, Jonathan Kozman, Maggie Neary, Meaghan K. Brody, Arthur L. TI A positive relationship between harm avoidance and brain nicotinic acetylcholine receptor availability SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Harm avoidance; Temperament and Character Inventory; Tobacco; Nicotine dependence; Positron emission tomography; Nicotinic acetylcholine receptor ID POSITRON-EMISSION-TOMOGRAPHY; INDUCED DOPAMINE RELEASE; ANXIETY-LIKE BEHAVIOR; PERSONALITY-TRAITS; (S)-3-METHYL-5-(1-METHYL-2-PYRROLIDINYL)ISOXAZOLE ABT-418; PSYCHOBIOLOGICAL APPROACH; ANXIOLYTIC ACTIVITIES; CHARACTER INVENTORY; DORSAL HIPPOCAMPUS; CHOLINERGIC LIGAND AB Prior research indicates that disturbance of cholinergic neurotransmission reduces anxiety, leading to the hypothesis that people with heightened cholinergic function have a greater tendency toward anxiety-like and/or harm-avoidant behavior. We sought to determine if people with elevated levels of harm avoidance (HA), a dimension of temperament from the Temperament and Character Inventory (TCI), have high alpha 4 beta 2* nicotinic acetylcholine receptor (nAChR) availability. Healthy adults (n = 10 5; 47 non-smokers and 58 smokers) underwent bolus-plus-continuous infusion positron emission tomography (PET) scanning using the radiotracer 2-[8F]fluoro-3-(2(S)azetidinylmethoxy) pyridine (abbreviated as 2-FA). During the uptake period of 2-FA, participants completed the TCI The central study analysis revealed a significant association between total HA and mean nAChR availability, with higher total HA scores being linked with greater nAChR availability. In examining HA subscales, both 'Fear of Uncertainty' and 'Fatigability' were significant, based on higher levels of these characteristics being associated with greater nAChR availabilities. This study adds to a growing body of knowledge concerning the biological basis of personality and may prove useful in understanding the pathophysiology of psychiatric disorders (such as anxiety disorders) that have similar characteristics to HA. Study findings may indicate that heightened cholinergic neurotransmission is associated with increased anxiety-like traits. Published by Elsevier Ireland Ltd. C1 [Storage, Steven; Brody, Arthur L.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA. [Storage, Steven; Mandelkern, Mark A.; Phuong, Jonathan; Kozman, Maggie; Neary, Meaghan K.; Brody, Arthur L.] VA Greater Los Angeles Healthcare Syst, Dept Res, Los Angeles, CA USA. [Mandelkern, Mark A.] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. [Brody, Arthur L.] VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. RP Brody, AL (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, 300 UCLA Med Plaza,Suite 2200, Los Angeles, CA 90095 USA. EM abrody@ucla.edu FU Tobacco Related Disease Research Program [19XT-0135]; National Institute on Drug Abuse [R01 DA20872]; Department of Veterans Affairs FX This study was supported by the Tobacco Related Disease Research Program (ALB. [19XT-0135]), the National Institute on Drug Abuse (A.L.B. [R01 DA20872]), and the Department of Veterans Affairs (Merit Review Award [A.L.B.I]). The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. The authors report no biomedical financial disclosures or potential conflicts of interest. NR 88 TC 4 Z9 4 U1 2 U2 81 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 EI 1872-7506 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD DEC 30 PY 2013 VL 214 IS 3 BP 415 EP 421 DI 10.1016/j.pscychresns.2013.07.010 PG 7 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 259MS UT WOS:000327531600031 PM 24148908 ER PT J AU Pena-Cruz, V Etemad, B Chatziandreou, N Nyein, PH Stock, S Reynolds, SJ Laeyendecker, O Gray, RH Serwadda, D Lee, SJ Quinn, TC Sagar, M AF Pena-Cruz, Victor Etemad, Behzad Chatziandreou, Nikolaos Phyu Hninn Nyein Stock, Shannon Reynolds, Steven J. Laeyendecker, Oliver Gray, Ronald H. Serwadda, David Lee, Sandra J. Quinn, Thomas C. Sagar, Manish TI HIV-1 envelope replication and alpha 4 beta 7 utilization among newly infected subjects and their corresponding heterosexual partners SO RETROVIROLOGY LA English DT Article DE HIV-1; Envelope; Transmission; Receptor; Replication; Alpha4 beta7; Dendritic cells; Langerhans cells; Selection ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN LANGERHANS CELLS; FUSION INHIBITOR T-20; DENDRITIC CELLS; T-CELLS; CORECEPTOR USAGE; TRANS-INFECTION; GENITAL-TRACT; NEUTRALIZATION SENSITIVITY; INTEGRIN ALPHA(4)BETA(7) AB Background: Previous studies suggest that active selection limits the number of HIV-1 variants acquired by a newly infected individual from the diverse variants circulating in the transmitting partner. We compared HIV-1 envelopes from 9 newly infected subjects and their linked transmitting partner to explore potential mechanisms for selection. Results: Recipient virus envelopes had significant genotypic differences compared to those present in the transmitting partner. Recombinant viruses incorporating pools of recipient and transmitter envelopes showed no significant difference in their sensitivity to receptor and fusion inhibitors, suggesting they had relatively similar entry capacity in the presence of low CD4 and CCR5 levels. Aggregate results in primary cells from up to 4 different blood or skin donors showed that viruses with envelopes from the transmitting partner as compared to recipient envelopes replicated more efficiently in CD4+ T cells, monocyte derived dendritic cell (MDDC) - CD4+ T cell co-cultures, Langerhans cells (LCs) - CD4+ T cell co-cultures and CD4+ T cells expressing high levels of the gut homing receptor, alpha 4 beta 7, and demonstrated greater binding to alpha 4 beta 7 high / CD8+ T cells. These transmitter versus recipient envelope virus phenotypic differences, however, were not always consistent among the primary cells from all the different blood or skin donation volunteers. Conclusion: Although genotypically unique variants are present in newly infected individuals compared to the diverse swarm circulating in the chronically infected transmitting partner, replication in potential early target cells and receptor utilization either do not completely dictate this genetic selection, or these potential transmission phenotypes are lost very soon after HIV-1 acquisition. C1 [Pena-Cruz, Victor; Etemad, Behzad; Chatziandreou, Nikolaos; Phyu Hninn Nyein; Sagar, Manish] Boston Univ, Dept Med, Div Infect Dis, Boston, MA 02215 USA. [Stock, Shannon] Coll Holy Cross, Dept Math & Comp Sci, Worcester, MA 01610 USA. [Reynolds, Steven J.; Laeyendecker, Oliver; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Reynolds, Steven J.; Laeyendecker, Oliver; Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Gray, Ronald H.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda. [Lee, Sandra J.] Dana Farber Canc Ctr, Dept Biostat, Boston, MA USA. [Lee, Sandra J.] Dana Farber Canc Ctr, Dept Computat Biol, Boston, MA USA. [Sagar, Manish] Boston Univ, Boston, MA 02118 USA. RP Sagar, M (reprint author), Boston Univ, Dept Med, Div Infect Dis, Boston, MA 02215 USA. EM msagar@bu.edu OI Laeyendecker, Oliver/0000-0002-6429-4760 FU NIH [AI077473]; Division of Intramural Research, NIAID, NIH FX We thank all the subjects who have contributed samples for these studies as part of the Rakai Health Sciences Program. We thank Drs. Andrew Redd, James Arthos, and Suryaram Gummuluru for insightful comments on the manuscript. This study was supported by NIH grants AI077473 (MS) and by the Division of Intramural Research, NIAID, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 112 TC 10 Z9 10 U1 2 U2 5 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 26 PY 2013 VL 10 AR 162 DI 10.1186/1742-4690-10-162 PG 16 WC Virology SC Virology GA AB3OC UT WOS:000331699100001 PM 24369910 ER PT J AU Takahashi, K Moyo, P Chigweshe, L Chang, WC White, MR Hartshorn, KL AF Takahashi, Kazue Moyo, Patience Chigweshe, Lorencia Chang, Wei-Chuan White, Mitchel R. Hartshorn, Kevan L. TI Efficacy of recombinant chimeric lectins, consisting of mannose binding lectin and L-ficolin, against influenza A viral infection in mouse model study SO VIRUS RESEARCH LA English DT Article DE Influenza A virus; Inflammation Innate immunity; Mannose-binding lectin; Ficolin; Host response ID HEPATOCYTE GROWTH-FACTOR; VIRUS-INFECTION; INCREASES SUSCEPTIBILITY; SURFACTANT PROTEIN; EBOLA-VIRUS; II CELLS; IMMUNITY; CONGLUTININ; CONTRIBUTES; PNEUMONIA AB Influenza A virus infection could result in fatal complications. Although immunization is the most effective prevention it is not effective to pandemic infection and is less effective or not approved for certain age groups. Some influenza virus strains have developed resistance to antiviral agents. Thus, new therapeutic agents are urgently needed. We focused on innate immune molecules, including mannose-binding lectin (MBL). In order to optimize its antiviral activities, we have previously generated three recombinant chimeric lectins (RCL), by introducing portions of L-ficolin, another innate immune lectin. Our in vitro characterizations previously selected RCL2 and RCL3 for further investigations against viruses, including influenza viruses. Here, we examined efficacy of these lectins against infection with PR8 (Hi NI) influenza A virus using mouse model studies and a human tracheal epithelial cell system. Our results provide in vivo evidence that RCL3 is effective agent against influenza virus infection. The therapeutic mechanisms are in part by providing host protective responses mediated by cytokines. We conclude that RCL3 is a potential new innate immune anti-influenza virus therapeutic agent. (C) 2013 Elsevier B.V. All rights reserved. C1 [Takahashi, Kazue; Moyo, Patience; Chigweshe, Lorencia; Chang, Wei-Chuan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Dev Immunol,Dept Pediat, Boston, MA 02115 USA. [White, Mitchel R.; Hartshorn, Kevan L.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. RP Takahashi, K (reprint author), 55 Fruit St,GRJ1402, Boston, MA 02114 USA. EM ktakahashi1@partners.org FU National Institutes of Health National Institute of Allergy and Infectious Diseases [U01 A1074503] FX The work was supported by the National Institutes of Health National Institute of Allergy and Infectious Diseases [U01 A1074503]. We thank Enzon Pharmaceutical for providing a recombinant MBL. NR 31 TC 4 Z9 5 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 EI 1872-7492 J9 VIRUS RES JI Virus Res. PD DEC 26 PY 2013 VL 178 IS 2 BP 495 EP 501 DI 10.1016/j.virusres.2013.10.001 PG 7 WC Virology SC Virology GA 283SC UT WOS:000329266300037 PM 24140629 ER PT J AU Maki, T Liang, AC Miyamoto, N Lo, EH Arai, K AF Maki, Takakuni Liang, Anna C. Miyamoto, Nobukazu Lo, Eng H. Arai, Ken TI Mechanisms of oligodendrocyte regeneration from ventricular-subventricular zone-derived progenitor cells in white matter diseases SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Review DE oligodendrogenesis; oligodendrocyte precursor cells; vascular dementia; multiple sclerosis; demyelination; subventricular zone; neural stem/progenitor cells ID NEURAL STEM-CELLS; CHRONIC CEREBRAL HYPOPERFUSION; CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; ADULT OLFACTORY-BULB; BLOOD-VESSELS FORM; MULTIPLE-SCLEROSIS; PRECURSOR CELLS; GROWTH-FACTOR; TRANSCRIPTION FACTORS AB White matter dysfunction is an important part of many CNS disorders including multiple sclerosis (MS) and vascular dementia. Within injured areas, myelin loss and oligodendrocyte death may trigger endogenous attempts at regeneration. However, during disease progression, remyelination failure may eventually occur due to impaired survival/proliferation, migration/recruitment, and differentiation of oligodendrocyte precursor cells (OPCs). The ventricular-subventricular zone (V-SVZ) and the subgranular zone (SGZ) are the main sources of neural stem/progenitor cells (NSPCs), which can give rise to neurons as well as OPCs. Under normal conditions in the adult brain, the V-SVZ progenitors generate a large number of neurons with a small number of oligodendrocyte lineage cells. However, after demyelination, the fate of V-SVZ-derived progenitor cells shifts from neurons to OPCs, and these newly generated OPCs migrate to the demyelinating lesions to ease white matter damage. In this mini-review, we will summarize the recent studies on extrinsic (e.g., vasculature, extracellular matrix (ECM), cerebrospinal fluid (CSF)) and intrinsic (e.g., transcription factors, epigenetic modifiers) factors, which mediate oligodendrocyte generation from the V-SVZ progenitor cells. A deeper understanding of the mechanisms that regulate the fate of V-SVZ progenitor cells may lead to new therapeutic approaches for ameliorating white matter dysfunction and damage in CNS disorders. C1 [Arai, Ken] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Arai, K (reprint author), Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, MGH East 149-2401, Charlestown, MA 02129 USA. EM karai@partners.org FU National Institutes of Health FX Funding Sources: Supported in part by National Institutes of Health. NR 116 TC 21 Z9 22 U1 1 U2 19 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5102 J9 FRONT CELL NEUROSCI JI Front. Cell. Neurosci. PD DEC 26 PY 2013 VL 7 AR 275 DI 10.3389/fncel.2013.00275 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 282NQ UT WOS:000329179000001 PM 24421755 ER PT J AU Ikrar, T Guo, N He, KW Besnard, A Levinson, S Hill, A Lee, HK Hen, R Xu, XM Sahay, A AF Ikrar, Taruna Guo, Nannan He, Kaiwen Besnard, Antoine Levinson, Sally Hill, Alexis Lee, Hey-Kyoung Hen, Rene Xu, Xiangmin Sahay, Amar TI Adult neurogenesis modifies excitability of the dentate gyrus SO FRONTIERS IN NEURAL CIRCUITS LA English DT Article DE adult neurogenesis; dentate gyrus; pattern separation; dentate granule neurons; encoding; inhibition; excitability ID ENHANCED SYNAPTIC PLASTICITY; NEWLY GENERATED NEURONS; PATTERN SEPARATION; GRANULE CELLS; HIPPOCAMPAL NEUROGENESIS; IN-VITRO; BORN; RAT; INHIBITION; SYNAPSES AB Adult-born dentate granule neurons contribute to memory encoding functions of the dentate gyrus (DG) such as pattern separation. However, local circuit-mechanisms by which adult-born neurons partake in this process are poorly understood. Computational, neuroanatomical and electrophysiological studies suggest that sparseness of activation in the granule cell layer (GCL) is conducive for pattern separation. A sparse coding scheme is thought to facilitate the distribution of similar entorhinal inputs across the GCL to decorrelate overlapping representations and minimize interference. Here we used fast voltage-sensitive dye (VSD) imaging combined with laser photostimulation and electrical stimulation to examine how selectively increasing adult DG neurogenesis influences local circuit activity and excitability. We show that DG of mice with more adult-born neurons exhibits decreased strength of neuronal activation and more restricted excitation spread in GCL while maintaining effective output to CA3c. Conversely, blockade of adult hippocampal neurogenesis changed excitability of the DG in the opposite direction. Analysis of GABAergic inhibition onto mature dentate granule neurons in the DG of mice with more adult-born neurons shows a modest readjustment of perisomatic inhibitory synaptic gain without changes in overall inhibitory tone, presynaptic properties or GABAergic innervation pattern. Retroviral labeling of connectivity in mice with more adult-born neurons showed increased number of excitatory synaptic contacts of adult-born neurons onto hilar interneurons. Together, these studies demonstrate that adult hippocampal neurogenesis modifies excitability of mature dentate granule neurons and that this non-cell autonomous effect may be mediated by local circuit mechanisms such as excitatory drive onto hilar interneurons. Modulation of DG excitability by adult-born dentate granule neurons may enhance sparse coding in the GCL to influence pattern separation. C1 [Ikrar, Taruna; Xu, Xiangmin] Univ Calif Irvine, Sch Med, Dept Anat & Neurobiol, Irvine, CA 92697 USA. [Guo, Nannan; Besnard, Antoine; Levinson, Sally; Sahay, Amar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA USA. [He, Kaiwen; Lee, Hey-Kyoung] Univ Maryland, Dept Biol, College Pk, MD 20742 USA. [He, Kaiwen; Lee, Hey-Kyoung] Johns Hopkins Univ, Zanvyl Krieger Mind Brain Inst, Solomon H Snyder Dept Neurosci, Baltimore, MD USA. [Hill, Alexis; Hen, Rene] Columbia Univ, Dept Pharmacol, Dept Neurosci, Div Integrat Neurosci, New York, NY 10027 USA. [Hill, Alexis; Hen, Rene] Columbia Univ, Dept Pharmacol, Dept Psychiat, Div Integrat Neurosci, New York, NY 10027 USA. [Xu, Xiangmin] Univ Calif Irvine, Dept Biomed Engn, Irvine, CA USA. [Sahay, Amar] Harvard Univ, Harvard Stem Cell Inst, Boston, MA 02115 USA. [Sahay, Amar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. RP Xu, XM (reprint author), Univ Calif Irvine, Sch Med, Dept Anat & Neurobiol, Irvine, CA 92697 USA. EM xiangmix@uci.edu; sahay.amar@mgh.harvard.edu RI Ikrar, Taruna/I-3357-2014; OI Lee, Hey-Kyoung/0000-0002-5554-983X FU US National Institute of Health [R01-EY014882, R01 MH068542, R01-NS078434, 4R00MH086615-03]; Bettencourt Schueller Foundation and Philippe Foundation; NARSAD; New York Stem cell Initiative; Hope for Depression Research Foundation grants; NARSAD Young Investigator Award; Ellison Medical Foundation New Scholar in Aging; Whitehall Foundation grant FX The authors are supported by US National Institute of Health grant R01-EY014882 (Hey-Kyoung Lee); Bettencourt Schueller Foundation and Philippe Foundation (Antonie Besnard), NARSAD, the New York Stem cell Initiative, US National Institutes of Health grant R01 MH068542, and Hope for Depression Research Foundation grants (Rene Hen); US National Institutes of Health grant R01-NS078434 and a NARSAD Young Investigator Award (Xiangmin Xu); US National Institutes of Health grant 4R00MH086615-03, the Ellison Medical Foundation New Scholar in Aging and a Whitehall Foundation grant (Amar Sahay). Rene Hen is a consultant for Roche, Lundbeck and Servier Companies. Amar Sahay is a consultant for PsyBrain LLc. We are grateful to D. Chichung Lie, Alejandro Schinder and Shaouyu Ge for retroviral constructs, reagents and protocols for virus preparation. We would like to thank Raymand Kelleher, Helen Scharfman and members of our laboratories for their comments on the manuscript. NR 69 TC 26 Z9 26 U1 2 U2 17 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5110 J9 FRONT NEURAL CIRCUIT JI Front. Neural Circuits PD DEC 26 PY 2013 VL 7 AR UNSP 204 DI 10.3389/fncir.2013.00204 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 279KF UT WOS:000328958200001 PM 24421758 ER PT J AU Payer, B Rosenberg, M Yamaji, M Yabuta, Y Koyanagi-Aoi, M Hayashi, K Yamanaka, S Saitou, M Lee, JT AF Payer, Bernhard Rosenberg, Michael Yamaji, Masashi Yabuta, Yukihiro Koyanagi-Aoi, Michiyo Hayashi, Katsuhiko Yamanaka, Shinya Saitou, Mitinori Lee, Jeannie T. TI Tsix RNA and the Germline Factor, PRDM14, Link X Reactivation and Stem Cell Reprogramming SO MOLECULAR CELL LA English DT Article ID CHROMOSOME INACTIVATION; NAIVE PLURIPOTENCY; XIST REPRESSION; IN-VITRO; MOUSE; MICE; MECHANISMS; GENERATION; GENE; TRANSCRIPTION AB Transitions between pluripotent and differentiated states are marked by dramatic epigenetic changes. Cellular differentiation is tightly linked to X chromosome inactivation (XCI), whereas reprogramming to induced pluripotent stem cells (iPSCs) is associated with X chromosome reactivation (XCR). XCR reverses the silent state of the inactive X, occurring in mouse blastocysts and germ cells. In spite of its importance, little is known about underlying mechanisms. Here, we examine the role of the long noncoding Tsix RNA and the germline factor, PRDM14. In blastocysts, XCR is perturbed by mutation of either Tsix or Prdm14. In iPSCs, XCR is disrupted only by PRDM14 deficiency, which also affects iPSC derivation and maintenance. We show that Tsix and PRDM14 directly link XCR to pluripotency: first, PRDM14 represses Rnf12 by recruiting polycomb repressive complex 2; second, Tsix enables PRDM14 to bind Xist. Thus, our study provides functional and mechanistic links between cellular and X chromosome reprogramming. C1 [Payer, Bernhard; Rosenberg, Michael; Lee, Jeannie T.] Howard Hughes Med Inst, Boston, MA 02114 USA. [Payer, Bernhard; Rosenberg, Michael; Lee, Jeannie T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Payer, Bernhard; Rosenberg, Michael; Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Yamaji, Masashi; Yabuta, Yukihiro; Hayashi, Katsuhiko; Saitou, Mitinori] Kyoto Univ, Grad Sch Med, Dept Anat & Cell Biol, Sakyo Ku, Kyoto 6068501, Japan. [Yamaji, Masashi; Yabuta, Yukihiro; Saitou, Mitinori] JST, ERATO, Sakyo Ku, Kyoto 6068501, Japan. [Koyanagi-Aoi, Michiyo; Hayashi, Katsuhiko; Yamanaka, Shinya; Saitou, Mitinori] Kyoto Univ, Ctr iPS Cell Res & Applicat, Sakyo Ku, Kyoto 6068507, Japan. [Hayashi, Katsuhiko] JST, PRESTO, Sakyo Ku, Kyoto 6068501, Japan. [Yamanaka, Shinya] Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA. [Saitou, Mitinori] Kyoto Univ, Inst Integrated Cell Mat Sci, Sakyo Ku, Kyoto 6068501, Japan. RP Lee, JT (reprint author), Howard Hughes Med Inst, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu RI Payer, Bernhard/F-7353-2010 OI Payer, Bernhard/0000-0002-4694-2082 FU Human Frontier Science Program; Charles A. King Trust, Bank of America, Co-Trustee; NIH [R37-GM58839] FX We are grateful to all members of the Lee Lab for valuable discussions and suggestions. We would like to thank M. Stadtfeld, J. Polo, N. Maherali, E. Apostolou, M. Anguera, and K. Hochedlinger for critical advice on iPSC reprogramming; L. Prickett-Rice, S. Lahiri, M. Weglarz, and K. Folz-Donahue for cell sorting; H. Sunwoo for Xist-LNA probe; and Y. Ogawa for Xist-DNA probe. B.P. was funded by postdoctoral awards from the Human Frontier Science Program and the Charles A. King Trust, Bank of America, Co-Trustee. J.T.L. is supported by the NIH (R37-GM58839). J.T.L. is an Investigator of the Howard Hughes Medical Institute. S.Y. is a member without salary of the scientific advisory boards of iPierian, iPS Academia Japan, Megakaryon Corporation, and HEALIOS K. K. Japan. NR 56 TC 31 Z9 32 U1 1 U2 18 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 26 PY 2013 VL 52 IS 6 BP 805 EP 818 DI 10.1016/j.molcel.2013.10.023 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 282CT UT WOS:000329148600005 PM 24268575 ER PT J AU Pavlin, JA Burkom, HS Elbert, Y Lucero-Obusan, C Winston, CA Cox, KL Oda, G Lombardo, JS Holodniy, M AF Pavlin, Julie A. Burkom, Howard S. Elbert, Yevgeniy Lucero-Obusan, Cynthia Winston, Carla A. Cox, Kenneth L. Oda, Gina Lombardo, Joseph S. Holodniy, Mark TI Combining Surveillance Systems: Effective Merging of US Veteran and Military Health Data SO PLOS ONE LA English DT Article ID INFLUENZA AB Background: The U. S. Department of Veterans Affairs (VA) and Department of Defense (DoD) had more than 18 million healthcare beneficiaries in 2011. Both Departments conduct individual surveillance for disease events and health threats. Methods: We performed joint and separate analyses of VA and DoD outpatient visit data from October 2006 through September 2010 to demonstrate geographic and demographic coverage, timeliness of influenza epidemic awareness, and impact on spatial cluster detection achieved from a joint VA and DoD biosurveillance platform. Results: Although VA coverage is greater, DoD visit volume is comparable or greater. Detection of outbreaks was better in DoD data for 58% and 75% of geographic areas surveyed for seasonal and pandemic influenza, respectively, and better in VA data for 34% and 15%. The VA system tended to alert earlier with a typical H3N2 seasonal influenza affecting older patients, and the DoD performed better during the H1N1 pandemic which affected younger patients more than normal influenza seasons. Retrospective analysis of known outbreaks demonstrated clustering evidence found in separate DoD and VA runs, which persisted with combined data sets. Conclusion: The analyses demonstrate two complementary surveillance systems with evident benefits for the national health picture. Relative timeliness of reporting could be improved in 92% of geographic areas with access to both systems, and more information provided in areas where only one type of facility exists. Combining DoD and VA data enhances geographic cluster detection capability without loss of sensitivity to events isolated in either population and has a manageable effect on customary alert rates. C1 [Pavlin, Julie A.] US Dept Def, Armed Forces Hlth Surveillance Ctr, Silver Spring, MD 20910 USA. [Burkom, Howard S.; Elbert, Yevgeniy; Lombardo, Joseph S.] Johns Hopkins Univ, Appl Phys Lab, Laurel, MD USA. [Lucero-Obusan, Cynthia; Winston, Carla A.; Oda, Gina] US Dept Vet Affairs, Off Publ Hlth, Washington, DC USA. [Cox, Kenneth L.] US Dept Def, US Army Inst Publ Hlth, Aberdeen Proving Ground, MD USA. RP Pavlin, JA (reprint author), US Dept Def, Armed Forces Hlth Surveillance Ctr, Silver Spring, MD 20910 USA. EM julie.a.pavlin.civ@mail.mil OI burkom, howard/0000-0003-0667-9467 FU Department of Veterans Affairs; Department of Defense FX This work was financially supported by intramural funding from the Departments of Veterans Affairs and Defense through the Joint Incentive Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 12 TC 5 Z9 5 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 26 PY 2013 VL 8 IS 12 AR e84077 DI 10.1371/journal.pone.0084077 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 281QS UT WOS:000329116700096 PM 24386335 ER PT J AU Slight, SP Seger, DL Nanji, KC Cho, I Maniam, N Dykes, PC Bates, DW AF Slight, Sarah P. Seger, Diane L. Nanji, Karen C. Cho, Insook Maniam, Nivethietha Dykes, Patricia C. Bates, David W. TI Are We Heeding the Warning Signs? Examining Providers' Overrides of Computerized Drug-Drug Interaction Alerts in Primary Care SO PLOS ONE LA English DT Article ID PHYSICIAN ORDER ENTRY; CLINICAL DECISION-SUPPORT; HUMAN-FACTORS PRINCIPLES; MEDICATION SAFETY; AMBULATORY-CARE; SYSTEMS; IMPLEMENTATION; ACCEPTANCE AB Background: Health IT can play a major role in improving patient safety. Computerized physician order entry with decision support can alert providers to potential prescribing errors. However, too many alerts can result in providers ignoring and overriding clinically important ones. Objective: To evaluate the appropriateness of providers' drug-drug interaction (DDI) alert overrides, the reasons why they chose to override these alerts, and what actions they took as a consequence of the alert. Design: A cross-sectional, observational study of DDI alerts generated over a three-year period between January 1st, 2009, and December 31st, 2011. Setting: Primary care practices affiliated with two Harvard teaching hospitals. The DDI alerts were screened to minimize the number of clinically unimportant warnings. Participants: A total of 24,849 DDI alerts were generated in the study period, with 40% accepted. The top 62 providers with the highest override rate were identified and eight overrides randomly selected for each (a total of 496 alert overrides for 438 patients, 3.3% of the sample). Results: Overall, 68.2% (338/496) of the DDI alert overrides were considered appropriate. Among inappropriate overrides, the therapeutic combinations put patients at increased risk of several specific conditions including: serotonin syndrome (21.5%, n=34), cardiotoxicity (16.5%, n=26), or sharp falls in blood pressure or significant hypotension (28.5%, n=45). A small number of drugs and DDIs accounted for a disproportionate share of alert overrides. Of the 121 appropriate alert overrides where the provider indicated they would "monitor as recommended", a detailed chart review revealed that only 35.5% (n=43) actually did. Providers sometimes reported that patients had already taken interacting medications together (15.7%, n=78), despite no evidence to confirm this. Conclusions and Relevance: We found that providers continue to override important and useful alerts that are likely to cause serious patient injuries, even when relatively few false positive alerts are displayed. C1 [Slight, Sarah P.; Cho, Insook; Dykes, Patricia C.; Bates, David W.] Brigham & Womens Hosp, Div Gen Internal Med, Ctr Patient Safety Res & Practice, Boston, MA 02115 USA. [Slight, Sarah P.] Univ Durham, Sch Med Pharm & Hlth, Durham, England. [Slight, Sarah P.; Nanji, Karen C.; Cho, Insook; Bates, David W.] Harvard Univ, Sch Med, Boston, MA USA. [Seger, Diane L.; Maniam, Nivethietha; Dykes, Patricia C.; Bates, David W.] Partners Healthcare Syst Inc, Boston, MA USA. [Nanji, Karen C.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Cho, Insook] Inha Univ, Dept Nursing, Inchon, South Korea. RP Slight, SP (reprint author), Brigham & Womens Hosp, Div Gen Internal Med, Ctr Patient Safety Res & Practice, 75 Francis St, Boston, MA 02115 USA. EM sslight@partners.org FU Agency for Healthcare Research and Quality (AHRQ) FX This study was funded by a grant from the Agency for Healthcare Research and Quality (AHRQ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 18 TC 18 Z9 19 U1 3 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 26 PY 2013 VL 8 IS 12 AR e85071 DI 10.1371/journal.pone.0085071 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 281QS UT WOS:000329116700130 PM 24386447 ER PT J AU Smith, AK Lo, B Aronson, L AF Smith, Alexander K. Lo, Bernard Aronson, Louise TI Elder Self-Neglect - How Can a Physician Help? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ABUSE; RISK AB Clinicians often expend considerable effort caring for elderly patients who neglect their own needs. But there are some practical approaches to the clinical care of self-neglecting patients. Mr. L. is a 96-year-old widower with critical aortic stenosis and mild cognitive impairment who had become increasingly short of breath and exhausted over the course of several weeks and needed 3 hours to get dressed on the day of admission. A concerned neighbor brought him to the hospital. He is not a candidate for aortic-valve replacement owing to poor functional status and coexisting conditions, and after several days of gentle diuresis, he can barely walk across the room. At the request of the primary care physician, Mr. L.'s son flies in for a family meeting to discuss discharge options. ... C1 [Smith, Alexander K.; Aronson, Louise] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94143 USA. [Smith, Alexander K.] San Francisco VA Med Ctr, San Francisco, CA USA. [Lo, Bernard] Greenwall Fdn Bioeth, New York, NY USA. RP Smith, AK (reprint author), Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94143 USA. FU NIA NIH HHS [P30 AG044281, K23 AG040772] NR 10 TC 3 Z9 3 U1 0 U2 5 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 26 PY 2013 VL 369 IS 26 BP 2476 EP 2479 DI 10.1056/NEJMp1310684 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 278BT UT WOS:000328863700005 PM 24369074 ER PT J AU Benzer, TI Nejad, SH Flood, JG AF Benzer, Theodore I. Nejad, Shamim H. Flood, James G. TI Case 40-2013: A 36-Year-Old Man with Agitation and Paranoia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID LIQUID-CHROMATOGRAPHY; TOXICOLOGY; DRUGS C1 [Benzer, Theodore I.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Nejad, Shamim H.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Flood, James G.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Benzer, Theodore I.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Nejad, Shamim H.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Flood, James G.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Benzer, TI (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. NR 12 TC 4 Z9 4 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 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 26 PY 2013 VL 369 IS 26 BP 2536 EP 2545 DI 10.1056/NEJMcpc1304051 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 278BT UT WOS:000328863700012 PM 24369079 ER PT J AU Jena, AB Sun, EC Romley, JA AF Jena, Anupam B. Sun, Eric C. Romley, John A. TI Mortality Among High-Risk Patients With Acute Myocardial Infarction Admitted to US Teaching-Intensive Hospitals in July A Retrospective Observational Study SO CIRCULATION LA English DT Article DE mortality; myocardial infarction ID DUTY HOUR REFORM; ACADEMIC CYCLE; EFFECT IMPACT; CARE; OUTCOMES; END; SURGERY; COHORT AB Background-Studies of whether inpatient mortality in US teaching hospitals rises in July as a result of organizational disruption and relative inexperience of new physicians (July effect) find small and mixed results, perhaps because study populations primarily include low-risk inpatients whose mortality outcomes are unlikely to exhibit a July effect. Methods and Results-Using the US Nationwide Inpatient sample, we estimated difference-in-difference models of mortality, percutaneous coronary intervention rates, and bleeding complication rates, for high-and low-risk patients with acute myocardial infarction admitted to 98 teaching-intensive and 1353 non-teaching-intensive hospitals during May and July 2002 to 2008. Among patients in the top quartile of predicted acute myocardial infarction mortality (high risk), adjusted mortality was lower in May than July in teaching-intensive hospitals (18.8% in May, 22.7% in July, P<0.01), but similar in non-teaching-intensive hospitals (22.5% in May, 22.8% in July, P=0.70). Among patients in the lowest three quartiles of predicted acute myocardial infarction mortality (low risk), adjusted mortality was similar in May and July in both teaching-intensive hospitals (2.1% in May, 1.9% in July, P=0.45) and non-teaching-intensive hospitals (2.7% in May, 2.8% in July, P=0.21). Differences in percutaneous coronary intervention and bleeding complication rates could not explain the observed July mortality effect among high risk patients. Conclusions-High-risk acute myocardial infarction patients experience similar mortality in teaching-and non-teaching-intensive hospitals in July, but lower mortality in teaching-intensive hospitals in May. Low-risk patients experience no such July effect in teaching-intensive hospitals. C1 [Jena, Anupam B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Hlth Care Policy,Dept Med, Cambridge, MA 02138 USA. [Jena, Anupam B.] Natl Bur Econ Res, Cambridge, MA 02138 USA. [Sun, Eric C.] Stanford Univ Hosp, Dept Anesthesia, Stanford, CA 94305 USA. [Romley, John A.] Univ So Calif, Leonard D Schaeffer Ctr Hlth Policy & Econ, Los Angeles, CA USA. [Romley, John A.] RAND Corp, Santa Monica, CA USA. RP Jena, AB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM jena@hcp.med.harvard.edu FU Office of the Director, National Institutes of Health [1DP5OD017897-01]; National Institute on Aging [1R03AG031990-A1]; Leonard Schaeffer Center for Health Policy and Economics at the University of Southern California FX Support was provided by the Office of the Director, National Institutes of Health (1DP5OD017897-01, to Dr Jena), by the National Institute on Aging (1R03AG031990-A1, to Dr Romley), and the Leonard Schaeffer Center for Health Policy and Economics at the University of Southern California (to Dr Romley). NR 24 TC 16 Z9 16 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 24 PY 2013 VL 128 IS 25 BP 2754 EP + DI 10.1161/CIRCULATIONAHA.113.004074 PG 13 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 298TT UT WOS:000330348100013 PM 24152859 ER PT J AU Kim, NH Delcroix, M Jenkins, DP Channick, R Dartevelle, P Jansa, P Lang, I Madani, MM Ogino, H Pengo, V Mayer, E AF Kim, Nick H. Delcroix, Marion Jenkins, David P. Channick, Richard Dartevelle, Philippe Jansa, Pavel Lang, Irene Madani, Michael M. Ogino, Hitoshi Pengo, Vittorio Mayer, Eckhard TI Chronic Thromboembolic Pulmonary Hypertension SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review DE chronic thromboembolic pulmonary hypertension; pulmonary endarterectomy; ventilation/perfusion scan; pulmonary angiogram ID EXTRACORPOREAL MEMBRANE-OXYGENATION; INTERNATIONAL PROSPECTIVE REGISTRY; SINGLE-CENTER EXPERIENCE; ART IMAGING TECHNIQUES; LONG-TERM TREATMENT; ARTERIAL-HYPERTENSION; COMPUTED-TOMOGRAPHY; CIRCULATORY ARREST; BOSENTAN THERAPY; LUNG PERFUSION AB Since the last World Symposium on Pulmonary Hypertension in 2008, we have witnessed numerous and exciting developments in chronic thromboembolic pulmonary hypertension (CTEPH). Emerging clinical data and advances in technology have led to reinforcing and updated guidance on diagnostic approaches to pulmonary hypertension, guidelines that we hope will lead to better recognition and more timely diagnosis of CTEPH. We have new data on treatment practices across international boundaries as well as long-term outcomes for CTEPH patients treated with or without pulmonary endarterectomy. Furthermore, we have expanded data on alternative treatment options for select CTEPH patients, including data from multiple clinical trials of medical therapy, including 1 recent pivotal trial, and compelling case series of percutaneous pulmonary angioplasty. Lastly, we have garnered more experience, and on a larger international scale, with pulmonary endarterectomy, which is the treatment of choice for operable CTEPH. This report overviews and highlights these important interval developments as deliberated among our task force of CTEPH experts and presented at the 2013 World Symposium on Pulmonary Hypertension in Nice, France. (C) 2013 by the American College of Cardiology Foundation C1 [Kim, Nick H.; Madani, Michael M.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Delcroix, Marion] Katholieke Univ Leuven Hosp, Cardiothorac Surg, Louvain, Belgium. [Jenkins, David P.] Papworth Hosp, Cambridge CB3 8RE, England. [Channick, Richard] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dartevelle, Philippe] Univ Paris 11, Le Plessis Robinson, France. [Jansa, Pavel] Charles Univ Prague, Prague, Czech Republic. [Lang, Irene] Med Univ Vienna, Vienna, Austria. [Ogino, Hitoshi] Tokyo Med Univ, Tokyo 1608402, Japan. [Pengo, Vittorio] Univ Padua, Padua, Italy. [Mayer, Eckhard] Max Planck Inst Physiol & Clin Res, Kerckhoff Klin, Bad Nauheim, Germany. RP Kim, NH (reprint author), Univ Calif San Diego, Div Pulm & Crit Care Med, 9300 Campus Point Dr,MC 7381, La Jolla, CA 92037 USA. EM h33kim@ucsd.edu OI Pengo, Vittorio/0000-0003-2064-6071 FU Actelion; Bayer; GlaxoSmithKline; Novartis; Pfizer; United Therapeutics; Actelion Pharmaceuticals; Gilead; AOP Orphan Pharmaceuticals; Bayer AG; Roche Diagnostics FX Dr. Delcroix has received fees for serving as investigator, speaker, consultant, or steering committee member from Actelion, Bayer, GlaxoSmithKline, Novartis, Pfizer, and United Therapeutics; educational grants from Actelion, GlaxoSmithKline, and Pfizer; research grants from Actelion, Pfizer, and GlaxoSmithKline; and she is also holder of the Actelion Chair for Pulmonary Hypertension and of the GlaxoSmithKline chair for research and education in pulmonary vascular pathology at the KU Leuven. Dr. Jenkins has received fees for lecturing and/or serving as a trial adjudicator and steering committee member from Actelion, Bayer, GlaxoSmithKline, and Pfizer. Dr. Channick has received research grants from and/ or consulted for companies that have treatments for pulmonary hypertension, including Actelion Pharmaceuticals, Bayer, United Therapeutics, and Gilead. Dr. Jansa has received fees for serving as investigator, consultant, and speaker from Actelion, Bayer, United Therapeutics, AOP Orphan Pharmaceuticals, Pfizer, and GlaxoSmithKline. Dr. Lang has received fees for serving as investigator, speaker, consultant, or steering committee member from Actelion, Bayer, GlaxoSmithKline, Novartis, Pfizer, AOP Orphan Pharmaceuticals, and United Therapeutics; educational grants from Actelion; and research grants from Actelion, AOP Orphan Pharmaceuticals, Bayer, and United Therapeutics. Dr. Madani has served as consultant for Bayer and GlaxoSmithKline; and received fees as speaker for Bayer. Dr. Pengo is on the advisory board of DaiichiSankyo; and has received lecture fees from Bayer AG and Roche Diagnostics. Dr. Mayer received fees for serving as speaker, consultant, or steering or adjudication committee member from Actelion, Bayer, GlaxoSmithKline, Pfizer, and AOP Orphan Pharmaceuticals. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 65 TC 145 Z9 149 U1 4 U2 22 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 24 PY 2013 VL 62 IS 25 SU S BP D92 EP D99 DI 10.1016/j.jacc.2013.10.024 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 286HW UT WOS:000329459400011 PM 24355646 ER PT J AU Seeger, W Adir, Y Barbera, JA Champion, H Coghlan, JG Cottin, V De Marco, T Galie, N Ghio, S Gibbs, S Martinez, FJ Semigran, MJ Simonneau, G Wells, AU Vachiery, JL AF Seeger, Werner Adir, Yochai Albert Barbera, Joan Champion, Hunter Coghlan, John Gerard Cottin, Vincent De Marco, Teresa Galie, Nazzareno Ghio, Stefano Gibbs, Simon Martinez, Fernando J. Semigran, Marc J. Simonneau, Gerald Wells, Athol U. Vachiery, Jean-Luc TI Pulmonary Hypertension in Chronic Lung Diseases SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review DE combined pulmonary fibrosis and emphysema; COPD; exhausted circulatory reserve; exhausted ventilatory reserve; lung fibrosis; pulmonary hypertension in chronic lung disease ID BRAIN NATRIURETIC PEPTIDE; INHALED NITRIC-OXIDE; TERM OXYGEN-THERAPY; ARTERIAL-HYPERTENSION; CONTROLLED-TRIAL; CLINICAL CHARACTERISTICS; EXERCISE CAPACITY; GAS-EXCHANGE; FIBROSIS; SARCOIDOSIS AB Chronic obstructive lung disease (COPD) and diffuse parenchymal lung diseases (DPLD), including idiopathic pulmonary fibrosis (IPF) and sarcoidosis, are associated with a high incidence of pulmonary hypertension (PH), which is linked with exercise limitation and a worse prognosis. Patients with combined pulmonary fibrosis and emphysema (CPFE) are particularly prone to the development of PH. Echocardiography and right heart catheterization are the principal modalities for the diagnosis of COPD and DPLD. For discrimination between group 1 PH patients with concomitant respiratory abnormalities and group 3 PH patients (PH caused by lung disease), patients should be transferred to a center with expertise in both PH and lung diseases for comprehensive evaluation. The task force encompassing the authors of this article provided criteria for this discrimination and suggested using the following definitions for group 3 patients, as exemplified for COPD, IPF, and CPFE: COPD/IPF/CPFE without PH (mean pulmonary artery pressure [mPAP] <25 mmHg); COPD/IPF/CPFE with PH (mPAP >= 25 mm Hg); PH-COPD, PH-IPF, and PH-CPFE); COPD/IPF/CPFE with severe PH (mPAP >= 35 mm Hg or mPAP >= 25 mm Hg with low cardiac index [CI<2.0 l/min/m(2)]; severe PH-COPD, severe PH-IPF, and severe PH-CPFE). The "severe PH group" includes only a minority of chronic lung disease patients who are suspected of having strong general vascular abnormalities (remodeling) accompanying the parenchymal disease and with evidence of an exhausted circulatory reserve rather than an exhausted ventilatory reserve underlying the limitation of exercise capacity. Exertional dyspnea disproportionate to pulmonary function tests, low carbon monoxide diffusion capacity, and rapid decline of arterial oxygenation upon exercise are typical clinical features of this subgroup with poor prognosis. Studies evaluating the effect of pulmonary arterial hypertension drugs currently not approved for group 3 PH patients should focus on this severe PH group, and for the time being, these patients should be transferred to expert centers for individualized patient care. (C) 2013 by the American College of Cardiology Foundation C1 [Seeger, Werner] Univ Giessen, D-35444 Giessen, Germany. [Seeger, Werner] Marburg Lung Ctr UGMLC, Marburg, Germany. [Adir, Yochai] Technion Israel Inst Technol, Fac Med, Lady Davis Carmel Med Ctr, Pulm Div, Haifa, Israel. [Albert Barbera, Joan] Univ Barcelona, Hosp Clin IDIBAPS, Network Ctr Biomed Res Resp Dis, Barcelona, Spain. [Champion, Hunter] UPMC Montefiore Hosp, Pittsburgh, PA USA. [Coghlan, John Gerard] Royal Free Hosp, Dept Cardiol, London NW3 2QG, England. [Cottin, Vincent] Univ Lyon 1, Natl Reference Ctr Rare Pulm Dis,INRA, Reg Competence Ctr Severe Pulm Arterial Hypertens, Hosp Civils Lyon,Louis Pradel Hosp,Dept Resp Dis, F-69365 Lyon, France. [De Marco, Teresa] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Galie, Nazzareno] Bologna Univ Hosp, DIMES, Dept Expt Diagnost & Specialty Med, Bologna, Italy. [Ghio, Stefano] Fdn IRCCS Policlin San Matteo, Div Cardiol, Pavia, Italy. [Gibbs, Simon] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. [Gibbs, Simon] Hammersmith Hosp, Natl Pulm Hypertens Serv, Dept Cardiol, London, England. [Martinez, Fernando J.] Univ Michigan, Med Ctr, Div Pulm & Crit Care, Ann Arbor, MI USA. [Semigran, Marc J.] Massachusetts Gen Hosp, Heart Failure & Cardiac Transplantat Ctr, Boston, MA 02114 USA. [Simonneau, Gerald] Univ Paris 11, Hop Antoine Beclere, Ctr Natl Reference Malad Vasc Pulm, Clamart, France. [Wells, Athol U.] Royal Brompton & Harefield NHS Fdn Trust, London, England. [Vachiery, Jean-Luc] Univ Libre Brussels, Hop Erasme, Dept Cardiol, Brussels, Belgium. RP Seeger, W (reprint author), Univ Giessen, Klin Str 33, D-35444 Giessen, Germany. EM Werner.Seeger@UGMLC.de OI Barbera, Joan Albert/0000-0003-1469-4990; Galie, Nazzareno/0000-0003-4271-8670 FU Pfizer; Bayer HealthCare; Bayer Pharma AG; Actelion; Bayer; GlaxoSmithKline; Novartis; Aires Pharmaceuticals; United Therapeutics; Gilead FX Dr. Seeger has received speaker fees from Pfizer and Bayer HealthCare; and consultant fees from Bayer Pharma AG. Dr. Barbera has received honoraria and consultancy fees from Actelion, Bayer, GlaxoSmithKline, and Pfizer; and his institution has received research grants from Actelion, Bayer, GlaxoSmithKline, Novartis, and Pfizer. Dr. Champion has served as a consultant to Bayer, Gilead, and Pfizer; and has received research funding from Aires Pharmaceuticals. Dr. Coghlan has received consultancy and lecture fees and honoraria from Actelion, GlaxoSmithKline, Bayer, and United Therapeutics; and equipment support from Actelion. Dr. Cottin has received speaker's fees, funding for meetings, a grant to his institution for participation in trials, and fees as an advisory board member and consultant from Actelion, GlaxoSmithKline, and Pfizer. Dr. De Marco has received honoraria and consultancy fees from Actelion and Gilead; and has received research grants from United Therapeutics and Novartis. Dr. Galic has served on advisory boards of Eli Lilly, Actelion, Pfizer, Bayer-Schering, GlaxoSmithKline, and Novartis; has received speaker's fees from Eli Lilly, Pfizer, Bayer-Schering, and GlaxoSmithKline; and his institution has received grants from Actelion, Pfizer, Bayer-Schering, GlaxoSmithKline, and Novartis. Dr. Ghio has consulted for Actelion andPfizer. Dr. Gibbs has consulted for Gilead, Novartis, and Actelion; has served as an advisory board member with and received speaker's fees from Actelion, Bayer, GlaxoSmithKline, Pfizer, and United Therapeutics; and has received research funding from United Therapeutics. Dr. Martinez has served on advisory boards of Amgen, Boehringer Ingelheim, Carden Jennings, Forest Pharmaceuticals, GlaxoSmithKline, Ikaria, Jannsens, MedImmune, Merck, Nycomed/Takeda, Pfizer, and Vertex; has participated on steering committees or data and safety monitoring boards of Centocor, Forest, Gilead, GlaxoSmithKline, Jannsens, Nycomed/Takeda, and Stromedix; has participated in advisory teleconferences with American Institute for Research, Axon, Grey Healthcare, and Sudler and Hennessey; has served as a speaker for Bayer, Forest, GlaxoSmithKline, Nycomed and Takeda; has consulted in continuing medical education programs for Incite, Foundation for Improving Patient Care, Inova Health System, MedScape/WebMD, NACE, NCME, Peer Voice, Projects in Knowledge, St. John's Hospital, St. Mary's Hospital, University of Illinois/Chicago, University of Texas Southwestern, UpToDate, and Wayne State University; and has received royalties from Informa. Dr. Simonneau has financial relationships with Actelion, Bayer, Eli Lilly, Novartis, Pfizer, and GlaxoSmithKline; and has received consultancy and lecture fees from Actelion. Dr. Vahiery has received lecture fees from and served as an advisory board member for Actelion Pharmaceuticals, Bayer Schering Eli Lilly, GlaxoSmithKline, and Pfizer; and has received consultancy fees from Actelion Pharmaceuticals, Merck, Bayer Schering, GlaxoSmithKline, and Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 82 TC 105 Z9 108 U1 3 U2 32 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 24 PY 2013 VL 62 IS 25 SU S BP D109 EP D116 DI 10.1016/j.jacc.2013.10.036 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 286HW UT WOS:000329459400013 PM 24355635 ER PT J AU Vachiery, JL Adir, Y Barbera, JA Champion, H Coghlan, JG Cottin, V De Marco, T Galie, N Ghio, S Gibbs, JSR Martinez, F Semigran, M Simonneau, G Wells, A Seeger, W AF Vachiery, Jean-Luc Adir, Yochai Albert Barbera, Joan Champion, Hunter Coghlan, John Gerard Cottin, Vincent De Marco, Teresa Galie, Nazzareno Ghio, Stefano Gibbs, J. Simon R. Martinez, Fernando Semigran, Marc Simonneau, Gerald Wells, Athol Seeger, Werner TI Pulmonary Hypertension Due to Left Heart Diseases SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review DE clinical trials; heart failure; pulmonary hypertension; pulmonary vascular disease ID PRESERVED EJECTION FRACTION; PHOSPHODIESTERASE-5 INHIBITION; ARTERIAL-HYPERTENSION; EXERCISE HEMODYNAMICS; PRESSURE-GRADIENT; PROGNOSTIC VALUE; CONTROLLED TRIAL; CLINICAL-TRIAL; OXYGEN-UPTAKE; DOUBLE-BLIND AB Pulmonary hypertension (PH), a common complication of left heart diseases (LHD), negatively impacts symptoms, exercise capacity, and outcome. Although the true prevalence of PH-LHD is unknown, a subset of patients might present significant PH that cannot be explained by a passive increase in left-sided filling pressures. The term "out-of-proportion" PH has been used to identify that population without a clear definition, which has been found less than ideal and created confusion. We propose a change in terminology and a new definition of PH due to LHD. We suggest to abandon "out-of-proportion" PH and to distinguish "isolated post-capillary PH" from "post-capillary PH with a pre-capillary component" on the basis of the pressure difference between diastolic pulmonary artery pressure and pulmonary artery wedge pressure. Although there is no validated treatment for PH-LHD, we provide insights into management and discuss completed and randomized trials in this condition. Finally, we provide recommendations for future clinical trials to establish safety and efficacy of novel compounds to target this area of unmet medical need. (C) 2013 by the American College of Cardiology Foundation C1 [Vachiery, Jean-Luc] Univ Libre Brussels, Hop Erasme, Dept Cardiol, Brussels, Belgium. [Adir, Yochai] Technion Israel Inst Technol, Fac Med, Lady Davis Carmel Med Ctr, Div Pulm, Haifa, Israel. [Albert Barbera, Joan] Univ Barcelona, Network Ctr Biomed Res Resp Dis CIBERES, Hosp Clin IDIBAPS, Barcelona, Spain. [Champion, Hunter] Univ Pittsburgh, Montefiore Hosp, Med Ctr, Pittsburgh, PA 15213 USA. [Coghlan, John Gerard] Royal Free Hosp, Dept Cardiol, London NW3 2QG, England. [Cottin, Vincent] Univ Lyon 1, Reg Competence Ctr Severe Pulm Arterial Hypertens, Natl Reference Ctr Rare Pulm Dis, Louis Pradel Hosp,Dept Resp Dis,Hosp Civils Lyon, F-69365 Lyon, France. [De Marco, Teresa] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Galie, Nazzareno] Bologna Univ Hosp, Dept Expt Diagnost & Specialty Med DIMES, Bologna, Italy. [Ghio, Stefano] Fdn IRCCS Policlin San Matteo, Div Cardiol, Pavia, Italy. [Gibbs, J. Simon R.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. [Gibbs, J. Simon R.] Hammersmith Hosp, Natl Pulm Hypertens Serv, Dept Cardiol, London, England. [Martinez, Fernando] Univ Michigan, Med Ctr, Div Pulm & Crit Care, Ann Arbor, MI USA. [Semigran, Marc] Massachusetts Gen Hosp, MGH Heart Failure & Cardiac Transplantat Ctr, Boston, MA 02114 USA. [Simonneau, Gerald] Univ Paris 11, Hop Univ Bicetre, AP HP, Serv Pneumol,Lab Excellence Rech Medicament & Inn, Le Kremlin Bicetre, France. [Simonneau, Gerald] INSERM, F-94275 Le Kremlin Bicetre, France. [Wells, Athol] Royal Brompton & Harefield NHS Fdn Trust, London, England. [Seeger, Werner] UGMLC, Giessen, Germany. RP Vachiery, JL (reprint author), Erasme Univ Hosp, Dept Cardiol, 808 Route Lennick, B-1070 Brussels, Belgium. EM jvachier@ulb.ac.be OI Galie, Nazzareno/0000-0003-4271-8670; Barbera, Joan Albert/0000-0003-1469-4990 FU Actelion; Bayer Schering; GlaxoSmithKline; Bayer; Pfizer; Novartis; Aires Pharmaceuticals; GenenTech; United Therapeutics; Eli Lilly and Company; Bayer-Schering FX Dr. Vachiery is a consultant for Actelion Pharmaceuticals, BayerSchering, Eli Lilly, Merck, and GlaxoSmithKline; has received speaker fees from Actelion, Bayer Schering, and GlaxoSmithKline; and has received a research grant from Actelion. Dr. Barbera has received honoraria and consultancy fees from Actelion, Bayer, GlaxoSmithKline, and Pfizer; his institution has received research grants from Actelion, Bayer, GlaxoSmithKline, Novartis, and Pfizer. Dr. Champion has served as a consultant to Bayer, Gilead, and Pfizer; and has received research funding from Aires Pharmaceuticals. Dr. Coghlan has received consultancy fees, lecture fees, and honoraria from Actelion, GlaxoSmithKline, Bayer, GenenTech, and United Therapeutics; and equipment support from Actelion. Dr. Cottin has received fees from Actelion, GlaxoSmithKline, and Pfizer for speaking, advisory boards, meetings, and clinical trials. Dr. De Marco has received honoraria and consultancy fees from Actelion and Gilead; and has received research grants from United Therapeutics, Novartis, and Pfizer. Dr. Galie has served on the advisory boards of Eli Lilly, Actelion, Pfizer, Bayer-Schering, GlaxoSmithKline, and Novartis; has received speaker fees from Eli Lilly and Company, Pfizer, Bayer-Schering, and GlaxoSmithKline; and has received institutional grant support from Actelion, Pfizer, Bayer-Schering, GlaxoSmithKline, and Novartis. Dr. Ghio has consultancies with Actelion and Pfizer. Dr. Gibbs has received consultancy fees from Gilead, Novartis, and Actelion; has served on the advisory board and received speaker fees from Actelion, Bayer, GlaxoSmithKline, Pfizer, and United Therapeutics; and research funding from United Therapeutics. Dr. Martinez has served on the advisory boards of Amgen, Boehringer Ingelheim, Carden Jennings, Forest Pharmaceuticals, GlaxoSmithKline, Ikaria, Jannsens, MedImmune, Merck, Nycomed/Takeda, Pfizer, and Vertex; has served on steering committees or data and safety monitoring boards of Centocor, Forest, Gilead, GlaxoSmithKline, Jannsens, Nycomed/Takeda, and Stromedix; has served on teleconferences of American Institute for Research, Axon, Grey Healthcare, and Sudler and Hennessey; has received speaking fees from Bayer, Forest, GlaxoSmithKline, Nycomed/Takeda CME programs for CME Incite, Foundation for Improving Patient Care, Inova Health System, MedScape/WebMD, National Association of Colleges and Employers, National Conference on Medical Education, Peer Voice, Projects in Knowledge, St. John's Hospital, St. Mary's Hospital, University of Illinois/Chicago, University of Texas Southwestern, UpToDate, and Wayne State University; and has received royalties from Informa. Dr. Simonneau has relationships with Eli Lilly, Actelion, Bayer, Novartis, Pfizer, and GlaxoSmithKline. Dr. Wells has received consultancy fees and fees for delivering lectures from Actelion. Dr. Seeger has received speaker fees from Pfizer and Bayer HealthCare; and is a consultant for Bayer Pharma AG. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 52 TC 137 Z9 143 U1 7 U2 23 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 24 PY 2013 VL 62 IS 25 SU S BP D100 EP D108 DI 10.1016/j.jacc.2013.10.033 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 286HW UT WOS:000329459400012 PM 24355634 ER PT J AU Subramanian, S Emami, H Vucic, E Singh, P Vijayakumar, J Fifer, KM Alon, A Shankar, SS Farkouh, M Rudd, JHF Fayad, ZA Van Dyke, TE Tawakol, A AF Subramanian, Sharath Emami, Hamed Vucic, Esad Singh, Parmanand Vijayakumar, Jayanthi Fifer, Kenneth M. Alon, Achilles Shankar, Sudha S. Farkouh, Michael Rudd, James H. F. Fayad, Zahi A. Van Dyke, Thomas E. Tawakol, Ahmed TI High-Dose Atorvastatin Reduces Periodontal Inflammation A Novel Pleiotropic Effect of Statins SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE statins; atherosclerosis; imaging; nuclear medicine; inflammation ID POSITRON-EMISSION-TOMOGRAPHY; C-REACTIVE PROTEIN; ATHEROSCLEROTIC PLAQUE INFLAMMATION; RHEUMATOID-ARTHRITIS; CARDIOVASCULAR-DISEASE; IN-VIVO; ENDOTHELIAL DYSFUNCTION; CAROTID ATHEROSCLEROSIS; CONTROLLED-TRIAL; TOOTH LOSS AB Objectives The purpose of this study was to test whether high-dose statin treatment would result in a reduction in periodontal inflammation as assessed by F-18-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT). Background Periodontal disease (PD) is an independent risk factor for atherosclerosis. Methods Eighty-three adults with risk factors or with established atherosclerosis and who were not taking high-dose statins were randomized to atorvastatin 80 mg vs. 10 mg in a multicenter, double-blind trial to evaluate the impact of atorvastatin on arterial inflammation. Subjects were evaluated using FDG-PET/CT at baseline and at 4 and 12 weeks. Arterial and periodontal tracer activity was assessed while blinded to treatment allocation, clinical characteristics, and temporal sequence. Periodontal bone loss (an index of PD severity) was evaluated using contrast-enhanced CT images while blinded to clinical and imaging data. Results Seventy-one subjects completed the study, and 59 provided periodontal images for analysis. At baseline, areas of severe PD had higher target-to-background ratio (TBR) compared with areas without severe PD (mean TBR: 3.83 [95% confidence interval (CI): 3.36 to 4.30] vs. 3.18 [95% CI: 2.91 to 3.44], p = 0.004). After 12 weeks, there was a significant reduction in periodontal inflammation in patients randomized to atorvastatin 80 mg vs. 10 mg (Delta TBR 80 mg vs. 10 mg group: mean -0.43 [95% CI: -0.83 to -0.02], p = 0.04). Between-group differences were greater in patients with higher periodontal inflammation at baseline (mean -0.74 [95% CI: -1.29 to -0.19], p = 0.01) and in patients with severe bone loss at baseline (-0.61 [95% CI: -1.16 to -0.054], p = 0.03). Furthermore, the changes in periodontal inflammation correlated with changes in carotid inflammation (R = 0.61, p < 0.001). Conclusions High-dose atorvastatin reduces periodontal inflammation, suggesting a newly recognized effect of statins. Given the concomitant changes observed in periodontal and arterial inflammation, these data raise the possibility that a portion of that beneficial impact of statins on atherosclerosis relate to reductions in extra-arterial inflammation, for example, periodontitis. (Evaluate the Utility of 18FDG-PET as a Tool to Quantify Atherosclerotic Plaque; NCT00703261) (C) 2013 by the American College of Cardiology Foundation C1 [Subramanian, Sharath; Emami, Hamed; Vucic, Esad; Singh, Parmanand; Vijayakumar, Jayanthi; Fifer, Kenneth M.; Tawakol, Ahmed] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Subramanian, Sharath; Emami, Hamed; Vucic, Esad; Singh, Parmanand; Vijayakumar, Jayanthi; Fifer, Kenneth M.; Tawakol, Ahmed] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Alon, Achilles; Shankar, Sudha S.] Merck Sharp & Dohme Corp, Whitehouse Stn, NJ USA. [Farkouh, Michael] Univ Toronto, Peter Munk Cardiac Ctr, Toronto, ON, Canada. [Farkouh, Michael] Univ Toronto, Heart & Stroke Richard Lewar Ctr Excellence, Toronto, ON, Canada. [Rudd, James H. F.] Univ Cambridge, Div Cardiovasc Med, Cambridge, England. [Fayad, Zahi A.] Icahn Sch Med Mt Sinai, Translat & Mol Imaging Inst, New York, NY USA. [Van Dyke, Thomas E.] Forsyth Inst, Cambridge, MA USA. RP Tawakol, A (reprint author), Massachusetts Gen Hosp, Div Cardiol, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM atawakol@partners.org OI Rudd, James/0000-0003-2243-3117 FU Merck Co., Inc.; National Center for Advancing Translational Sciences (NIH) [8UL1TR000170-05]; Merck Sharp Dohme Corp; NIHR Cambridge Biomedical Research Center; Roche FX Merck & Co., Inc. provided funding for the study. The statistical analysis was conducted with consult from Harvard Catalyst which is supported by National Center for Research Resources and the National Center for Advancing Translational Sciences (NIH Award 8UL1TR000170-05). Drs. Alon and Shankar are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. Dr. Alon owns stock in Merck Sharp & Dohme Corp. Dr. Farkouh's institution received grants from Merck Sharp & Dohme Corp. Dr. Rudd is supported by the NIHR Cambridge Biomedical Research Center. Drs. Fayad and Tawakol received consulting fees and their institutions received grants from Roche and Merck Sharp & Dohme Corp. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Subramanian and Emami contributed equally to this work. Drs. Van Dyke and Tawakol also contributed equally to this work. NR 49 TC 37 Z9 37 U1 1 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 24 PY 2013 VL 62 IS 25 BP 2382 EP 2391 DI 10.1016/j.jacc.2013.08.1627 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 278QD UT WOS:000328903900006 PM 24070911 ER PT J AU Prentice-Mott, HV Chang, CH Mahadevan, L Mitchison, TJ Irimia, D Shah, JV AF Prentice-Mott, Harrison V. Chang, Chi-Han Mahadevan, L. Mitchison, Timothy J. Irimia, Daniel Shah, Jagesh V. TI Biased migration of confined neutrophil-like cells in asymmetric hydraulic environments SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cell migration; microfluidics; physical forces; cell confinement; photocaged chemoattractant ID EUKARYOTIC CHEMOTAXIS; MOTILITY; ADHESIONS; LEUKOCYTE; POLARITY; LINE AB Cells integrate multiple measurement modalities to navigate their environment. Soluble and substrate-bound chemical gradients and physical cues have all been shown to influence cell orientation and migration. Here we investigate the role of asymmetric hydraulic pressure in directional sensing. Cells confined in microchannels identified and chose a path of lower hydraulic resistance in the absence of chemical cues. In a bifurcating channel with asymmetric hydraulic resistances, this choice was preceded by the elaboration of two leading edges with a faster extension rate along the lower resistance channel. Retraction of the "losing" edge appeared to precipitate a final choice of direction. The pressure differences altering leading edge protrusion rates were small, suggesting weak force generation by leading edges. The response to the physical asymmetry was able to override a dynamically generated chemical cue. Motile cells may use this bias as a result of hydraulic resistance, or "barotaxis," in concert with chemotaxis to navigate complex environments. C1 [Prentice-Mott, Harrison V.; Chang, Chi-Han; Mitchison, Timothy J.; Shah, Jagesh V.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Prentice-Mott, Harrison V.; Chang, Chi-Han; Shah, Jagesh V.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. [Prentice-Mott, Harrison V.; Chang, Chi-Han; Shah, Jagesh V.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Prentice-Mott, Harrison V.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Chang, Chi-Han] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Mahadevan, L.] Harvard Univ, Dept Phys & Organism & Evolutionary Biol, Cambridge, MA 02138 USA. [Irimia, Daniel] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Irimia, Daniel] Shriners Hosp Children, Boston, MA 02114 USA. RP Shah, JV (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. EM jagesh@hms.harvard.edu OI Irimia, Daniel/0000-0001-7347-2082 FU National Institutes of Health [P41 EB002503]; Natural Sciences and Engineering Research Council of Canada (NSERC); Beckman Laser Institute Foundation; Brigham and Women's Hospital FX We thank members of the laboratory of J.V.S., especially Yinghua Guan and Mikhail Sergeev; Guillaume Charras (University College London), Tony Yu-Chen Tsai (Stanford University), and Gaudenz Danuser (Harvard Medical School) for helpful discussions and constructive comments; Lew Cantley (Harvard Medical School), Guillaume Charras (University College London), Paul Wiseman (McGill University), and Orion Wiener (University of California, San Francisco) for generously sharing reagents and software. All microfabrication was carried out in the National Institutes of Health-funded facility (Grant P41 EB002503) at the Charlestown Navy Yard at Massachusetts General Hospital. This work was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) (C.-H. C.). Work in the laboratory of J.V.S. is supported by a grant from the Beckman Laser Institute Foundation and funds from Brigham and Women's Hospital. NR 27 TC 20 Z9 20 U1 2 U2 20 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 24 PY 2013 VL 110 IS 52 BP 21006 EP 21011 DI 10.1073/pnas.1317441110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 277ZW UT WOS:000328858800045 PM 24324148 ER PT J AU Holderried, TAW Lang, PA Kim, HJ Cantor, H AF Holderried, Tobias A. W. Lang, Philipp A. Kim, Hye-Jung Cantor, Harvey TI Genetic disruption of CD8(+) Treg activity enhances the immune response to viral infection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE T-cell exhaustion; killer cell Ig-like receptor; immune regulation ID REGULATORY T-CELLS; LYMPHOCYTIC CHORIOMENINGITIS VIRUS; NATURAL-KILLER-CELLS; NK CELLS; MICE; PERSISTENCE; HEPATITIS; RECEPTOR; LCMV; IMMUNOLOGY AB The immunological interactions that regulate the T-cell response to chronic viral infection are insufficiently understood. Here we study a cellular interaction that may enhance the antiviral immune response and constrain immunopathology. We analyze the contribution of Qa-1-restricted CD8(+) regulatory T cells (Treg cells) to antiviral immunity after infection by lymphocytic choriomeningitis virus. These CD8(+) Treg cells recognize and eliminate target cells through an interaction with the murine class Ib MHC molecule Qa-1 (HLA-E in humans). Using Qa-1 mutant mice (B6.Qa-1-D227K [B6-DK]) that harbor a single mutation that abrogates binding of Qa-1 peptide to the CD8-TCR (T-cell receptor) complex, we show that disruption of immune suppression mediated by CD8(+) Treg cells results in robust antiviral immune responses in both acute and chronic viral infection. Enhanced antiviral responses of B6-DK mice were accompanied by increased control of virus, reduced tissue inflammation in the acute phase, and dramatic alleviation of disease in the chronic phase. In addition, CD8(+) effector T cells in B6-DK mice displayed a less exhausted phenotype characterized by decreased expression of programmed cell death 1 (PD-1), LAG3 (CD223), and 2B4 (CD244) and increased expression of NKG2D (CD314) and killer cell lectin-like receptor subfamily G member 1 (KLRG1). Enhanced antiviral immunity in B6-DK mice reflected, in part, reduced inhibition of CD8(+) effector cells by CD8(+) Treg cells. These findings indicate that direct inhibition of effector CD8(+) T cells by Qa-1-restricted CD8(+) Treg cells results in increased disease severity and delayed recovery. These data suggest that depletion or inactivation of CD8(+) Treg cells represents a potentially effective strategy to enhance protective immunity to chronic viral infection. C1 [Holderried, Tobias A. W.; Kim, Hye-Jung; Cantor, Harvey] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Holderried, Tobias A. W.; Kim, Hye-Jung; Cantor, Harvey] Harvard Univ, Sch Med, Div Immunol, Dept Microbiol & Immunol, Boston, MA 02215 USA. [Holderried, Tobias A. W.; Lang, Philipp A.] Univ Dusseldorf, Dept Gastroenterol Hepatol & Infect Dis, D-40025 Dusseldorf, Germany. RP Kim, HJ (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. EM Hye-Jung_Kim@dfci.harvard.edu; harvey_cantor@dfci.harvard.edu FU National Institutes of Health [AI 037562]; Alexander von Humboldt Foundation [SKA2010]; National Research Service Award Fellowship [T32CA070083]; LeRoy Schecter Research Foundation FX We thank U. von Andrian for LCMV Armstrong and clone 13; R. Bronson (Dana-Farber/Harvard Cancer Center Rodent Histopathology Core) for histology analysis; J. Daley, S. Lazo-Kallanian, and R. Smith for cytometry support; and A. Angel for manuscript and figure preparation. This work was supported in part by National Institutes of Health Research Grant (AI 037562) and a gift from the LeRoy Schecter Research Foundation (to H. C.), the Alexander von Humboldt Foundation (SKA2010; to P. A. L.), and National Research Service Award Fellowship (T32CA070083; to H.-J.K.). NR 36 TC 12 Z9 12 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 24 PY 2013 VL 110 IS 52 BP 21089 EP 21094 DI 10.1073/pnas.1320999110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 277ZW UT WOS:000328858800059 PM 24324159 ER PT J AU Ebi, H Costa, C Faber, AC Nishtala, M Kotani, H Juric, D Della Pelle, P Song, Y Yano, S Mino-Kenudson, M Benes, CH Engelman, JA AF Ebi, Hiromichi Costa, Carlotta Faber, Anthony C. Nishtala, Madhuri Kotani, Hiroshi Juric, Dejan Della Pelle, Patricia Song, Youngchul Yano, Seiji Mino-Kenudson, Mari Benes, Cyril H. Engelman, Jeffrey A. TI PI3K regulates MEK/ERK signaling in breast cancer via the Rac-GEF, P-Rex1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PATHWAY ACTIVATION; TYROSINE KINASES; IN-VIVO; INHIBITION; CELLS; MEK; APOPTOSIS; PI3K/MTOR; AKT; IDENTIFICATION AB The PI3K pathway is genetically altered in excess of 70% of breast cancers, largely through PIK3CA mutation and HER2 amplification. Preclinical studies have suggested that these subsets of breast cancers are particularly sensitive to PI3K inhibitors; however, the reasons for this heightened sensitivity are mainly unknown. We investigated the signaling effects of PI3K inhibition in PIK3CA mutant and HER2 amplified breast cancers using PI3K inhibitors currently in clinical trials. Unexpectedly, we found that in PIK3CA mutant and HER2 amplified breast cancers sensitive to PI3K inhibitors, PI3K inhibition led to a rapid suppression of Rac1/p21-activated kinase (PAK)/protein kinase C-RAF (C-RAF)/protein kinase MEK (MEK)/ERK signaling that did not involve RAS. Furthermore, PI3K inhibition led to an ERK-dependent up-regulation of the proapoptotic protein, BIM, followed by induction of apoptosis. Expression of a constitutively active form of Rac1 in these breast cancer models blocked PI3Ki-induced down-regulation of ERK phosphorylation, apoptosis, and mitigated PI3K inhibitor sensitivity in vivo. In contrast, protein kinase AKT inhibitors failed to block MEK/ERK signaling, did not up-regulate BIM, and failed to induce apoptosis. Finally, we identified phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 (P-Rex1) as the PI(3,4,5)P3-dependent guanine exchange factor for Rac1 responsible for regulation of the Rac1/C-RAF/MEK/ERK pathway in these cells. The expression level of P-Rex1 correlates with sensitivity to PI3K inhibitors in these breast cancer cell lines. Thus, PI3K inhibitors have enhanced activity in PIK3CA mutant and HER2 amplified breast cancers in which PI3K inhibition down-regulates both the AKT and Rac1/ERK pathways. In addition, P-Rex1 may serve as a biomarker to predict response to single-agent PI3K inhibitors within this subset of breast cancers. C1 [Ebi, Hiromichi; Costa, Carlotta; Faber, Anthony C.; Nishtala, Madhuri; Juric, Dejan; Della Pelle, Patricia; Song, Youngchul; Mino-Kenudson, Mari; Benes, Cyril H.; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Ebi, Hiromichi; Costa, Carlotta; Faber, Anthony C.; Nishtala, Madhuri; Juric, Dejan; Della Pelle, Patricia; Song, Youngchul; Mino-Kenudson, Mari; Benes, Cyril H.; Engelman, Jeffrey A.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Ebi, Hiromichi; Kotani, Hiroshi; Yano, Seiji] Kanazawa Univ, Canc Res Inst, Div Med Oncol, Kanazawa, Ishikawa 9200934, Japan. RP Engelman, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM jengelman@partners.org OI Ebi, Hiromichi/0000-0003-3155-7576 FU National Institutes of Health [R01CA137008, R01CA140594] FX We thank Matthew Niederst for careful reading of the manuscript, and the Targeting PI3K in Women's Cancers Stand Up to Cancer Dream Team for supplying GDC-0941. This study is supported by National Institutes of Health Grants R01CA137008 and R01CA140594 (to J.A.E.). NR 39 TC 52 Z9 54 U1 1 U2 26 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 24 PY 2013 VL 110 IS 52 BP 21124 EP 21129 DI 10.1073/pnas.1314124110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 277ZW UT WOS:000328858800065 PM 24327733 ER PT J AU Kim, MS Yamamoto, Y Kim, K Kamei, N Shimada, T Liu, L Moore, K Woo, JR Shoelson, SE Lee, J AF Kim, Myung-Sunny Yamamoto, Yasuhiko Kim, Kyungjin Kamei, Nozomu Shimada, Takeshi Liu, Libin Moore, Kristin Woo, Ju Rang Shoelson, Steven E. Lee, Jongsoon TI Regulation of Diet-Induced Adipose Tissue and Systemic Inflammation by Salicylates and Pioglitazone SO PLOS ONE LA English DT Article ID INDUCED INSULIN-RESISTANCE; BLOOD-CELL COUNT; DIABETES-MELLITUS; RANDOMIZED-TRIAL; IKK-BETA; OBESITY; MONOCYTES; MACROPHAGES; SALSALATE; DISEASE AB It is increasingly accepted that chronic inflammation participates in obesity-induced insulin resistance and type 2 diabetes (T2D). Salicylates and thiazolidinediones (TZDs) both have anti-inflammatory and anti-hyperglycemic properties. The present study compared the effects of these drugs on obesity-induced inflammation in adipose tissue (AT) and AT macrophages (ATMs), as well as the metabolic and immunological phenotypes of the animal models. Both drugs improved high fat diet (HFD)-induced insulin resistance. However, salicylates did not affect AT and ATM inflammation, whereas Pioglitazone improved these parameters. Interestingly, HFD and the drug treatments all modulated systemic inflammation as assessed by changes in circulating immune cell numbers and activation states. HFD increased the numbers of circulating white blood cells, neutrophils, and a pro-inflammatory monocyte subpopulation (Ly6C(hi)), whereas salicylates and Pioglitazone normalized these cell numbers. The drug treatments also decreased circulating lymphocyte numbers. These data suggest that obesity induces systemic inflammation by regulating circulating immune cell phenotypes and that antidiabetic interventions suppress systemic inflammation by normalizing circulating immune phenotypes. C1 [Kim, Myung-Sunny; Yamamoto, Yasuhiko; Kim, Kyungjin; Kamei, Nozomu; Shimada, Takeshi; Liu, Libin; Moore, Kristin; Woo, Ju Rang; Shoelson, Steven E.; Lee, Jongsoon] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Kim, Myung-Sunny; Yamamoto, Yasuhiko; Kim, Kyungjin; Kamei, Nozomu; Shimada, Takeshi; Liu, Libin; Moore, Kristin; Woo, Ju Rang; Shoelson, Steven E.; Lee, Jongsoon] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Kim, Myung-Sunny] Korea Food Res Inst, Songnam, South Korea. [Yamamoto, Yasuhiko] Kanazawa Univ, Grad Sch Med Sci, Kanazawa, Ishikawa, Japan. RP Shoelson, SE (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. EM steven.shoelson@joslin.harvard.edu; jongsoon.lee@joslin.harvard.edu FU National Institutes of Health (NIH) [R21 DK80380, P30 DK046200]; American Diabetes Association [RA 110BS97]; NIH [R01 DK45943, R37 DK51729, R01 DK73547, P30 DK36836]; Helen and Morton Adler Chair FX These studies were supported by National Institutes of Health (NIH) R21 DK80380 and P30 DK046200 (Pilot and Feasibility awards from the Boston Obesity Nutrition Research Center) and the American Diabetes Association grant RA 110BS97 to J.L.; NIH R01 DK45943, R37 DK51729, and R01 DK73547 to S.E.S.; NIH P30 DK36836 (Joslin Diabetes Research Center), and the Helen and Morton Adler Chair (S.E.S.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 30 TC 6 Z9 7 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 23 PY 2013 VL 8 IS 12 AR e82847 DI 10.1371/journal.pone.0082847 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AM5FG UT WOS:000339881300001 PM 24376593 ER PT J AU Elagib, KE Rubinstein, JD Delehanty, LL Ngoh, VS Greer, PA Li, SR Lee, JK Li, Z Orkin, SH Mihaylov, IS Goldfarb, AN AF Elagib, Kamaleldin E. Rubinstein, Jeremy D. Delehanty, Lorrie L. Ngoh, Valerie S. Greer, Peter A. Li, Shuran Lee, Jae K. Li, Zhe Orkin, Stuart H. Mihaylov, Ivailo S. Goldfarb, Adam N. TI Calpain 2 Activation of P-TEFb Drives Megakaryocyte Morphogenesis and Is Disrupted by Leukemogenic GATA1 Mutation SO DEVELOPMENTAL CELL LA English DT Article ID ELONGATION-FACTOR-B; GENE-EXPRESSION; TRANSCRIPTION ELONGATION; 7SK SNRNA; ALPHA-ACTININ; DIFFERENTIATION; HYPERTROPHY; MATURATION; HEXIM1; MOUSE AB Megakaryocyte morphogenesis employs a "hypertrophy-like" developmental program that is dependent on P-TEFb kinase activation and cytoskeletal remodeling. P-TEFb activation classically occurs by a feedback-regulated process of signal-induced, reversible release of active Cdk9-cyclin T modules from large, inactive 7SK small nuclear ribonucleoprotein particle (snRNP) complexes. Here, we have identified an alternative pathway of irreversible P-TEFb activation in megakaryopoiesis that is mediated by dissolution of the 7SK snRNP complex. In this pathway, calpain 2 cleavage of the core 7SK snRNP component MePCE promoted P-TEFb release and consequent upregulation of a cohort of cytoskeleton remodeling factors, including alpha-actinin-1. In a subset of human megakaryocytic leukemias, the transcription factor GATA1 undergoes truncating mutation (GATA1s). Here, we linked the GATA1s mutation to defects in megakaryocytic upregulation of calpain 2 and of P-TEFb-dependent cytoskeletal remodeling factors. Restoring calpain 2 expression in GATA1s mutant megakaryocytes rescued normal development, implicating this morphogenetic pathway as a target in human leukemogenesis. C1 [Elagib, Kamaleldin E.; Rubinstein, Jeremy D.; Delehanty, Lorrie L.; Ngoh, Valerie S.; Mihaylov, Ivailo S.; Goldfarb, Adam N.] Univ Virginia, Sch Med, Dept Pathol, Charlottesville, VA 22908 USA. [Greer, Peter A.] Queens Univ, Dept Pathol & Mol Med, Kingston, ON K7L 3N6, Canada. [Li, Shuran; Lee, Jae K.] Univ Virginia, Sch Med, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA. [Li, Zhe; Orkin, Stuart H.] Harvard Univ, Sch Med, Div Hematol Oncol, Childrens Hosp Boston,Harvard Stem Cell Inst, Boston, MA 02115 USA. [Li, Zhe; Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol,Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Goldfarb, AN (reprint author), Univ Virginia, Sch Med, Dept Pathol, Charlottesville, VA 22908 USA. EM ang3x@virginia.edu FU National Institutes of Health [CA100057, DK079924, DK090926] FX This paper is dedicated to the memory of Marcia Finberg. We thank Dr. Matjaz Barboric for the FLAG-MePCE expression construct, Dr. Leif Carlsson for HPC7 cells, Dr. Didier Trono for lentiviral plasmids, and Daniel Matson for generous assistance with glycerol gradient analysis. For helpful discussions and advice, we thank Drs. B. Matija Peterlin, David Price, Prabu Reddi, and Vijay Sankaran. This work was supported by grants from the National Institutes of Health (CA100057, DK079924, and DK090926). NR 54 TC 7 Z9 7 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 EI 1878-1551 J9 DEV CELL JI Dev. Cell PD DEC 23 PY 2013 VL 27 IS 6 BP 607 EP 620 DI 10.1016/j.devcel.2013.11.013 PG 14 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 281RB UT WOS:000329117600004 PM 24369834 ER PT J AU Meir, JU Robinson, PW Vilchis, LI Kooyman, GL Costa, DP Ponganis, PJ AF Meir, Jessica U. Robinson, Patrick W. Vilchis, L. Ignacio Kooyman, Gerald L. Costa, Daniel P. Ponganis, Paul J. TI Blood Oxygen Depletion Is Independent of Dive Function in a Deep Diving Vertebrate, the Northern Elephant Seal SO PLOS ONE LA English DT Article ID BOTTLE-NOSED DOLPHINS; EMPEROR PENGUINS; TURSIOPS-TRUNCATUS; MARINE PREDATOR; BEHAVIOR; THERMOREGULATION; PATTERNS; WHALES; COST AB Although energetics is fundamental to animal ecology, traditional methods of determining metabolic rate are neither direct nor instantaneous. Recently, continuous blood oxygen (O-2) measurements were used to assess energy expenditure in diving elephant seals (Mirounga angustirostris), demonstrating that an exceptional hypoxemic tolerance and exquisite management of blood O-2 stores underlie the extraordinary diving capability of this consummate diver. As the detailed relationship of energy expenditure and dive behavior remains unknown, we integrated behavior, ecology, and physiology to characterize the costs of different types of dives of elephant seals. Elephant seal dive profiles were analyzed and O-2 utilization was classified according to dive type (overall function of dive: transit, foraging, food processing/rest). This is the first account linking behavior at this level with in vivo blood O-2 measurements in an animal freely diving at sea, allowing us to assess patterns of O-2 utilization and energy expenditure between various behaviors and activities in an animal in the wild. In routine dives of elephant seals, the blood O-2 store was significantly depleted to a similar range irrespective of dive function, suggesting that all dive types have equal costs in terms of blood O-2 depletion. Here, we present the first physiological evidence that all dive types have similarly high blood O-2 demands, supporting an energy balance strategy achieved by devoting one major task to a given dive, thereby separating dive functions into distinct dive types. This strategy may optimize O-2 store utilization and recovery, consequently maximizing time underwater and allowing these animals to take full advantage of their underwater resources. This approach may be important to optimizing energy expenditure throughout a dive bout or at-sea foraging trip and is well suited to the lifestyle of an elephant seal, which spends >90% of its time at sea submerged making diving its most "natural" state. C1 [Meir, Jessica U.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. [Robinson, Patrick W.; Costa, Daniel P.] Univ Calif Santa Cruz, Dept Ecol & Evolutionary Biol, Santa Cruz, CA 95064 USA. [Vilchis, L. Ignacio; Kooyman, Gerald L.; Ponganis, Paul J.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA. RP Meir, JU (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. EM jmeir@mgh.harvard.edu FU National Science Foundation Integrative Organismal Systems (IOS) [0641801]; Office of Naval Research [N00014-08-1-1195] FX Funding was provided by National Science Foundation Integrative Organismal Systems (IOS) Grant # 0641801, Office of Naval Research grant # N00014-08-1-1195. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 35 TC 4 Z9 4 U1 1 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 23 PY 2013 VL 8 IS 12 AR e83248 DI 10.1371/journal.pone.0083248 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 278IG UT WOS:000328882000075 PM 24376671 ER PT J AU Meynard, D Sun, CC Wu, QF Chen, WJ Chen, SZ Nelson, CN Waters, MJ Babitt, JL Lin, HY AF Meynard, Delphine Sun, Chia Chi Wu, Qifang Chen, Wenjie Chen, Shanzhuo Nelson, Caroline N. Waters, Michael J. Babitt, Jodie L. Lin, Herbert Y. TI Inflammation Regulates TMPRSS6 Expression via STAT5 SO PLOS ONE LA English DT Article ID IRON-DEFICIENCY ANEMIA; MATRIPTASE-2 TMPRSS6; HEPCIDIN EXPRESSION; CHRONIC DISEASE; BINDING; CELLS; MICE; FERROPORTIN; HEMOJUVELIN; PROTEINS AB TMPRSS6 is a regulated gene, with a crucial role in the regulation of iron homeostasis by inhibiting hepcidin expression. The main regulator of iron homeostasis, the antimicrobial peptide hepcidin, which also has a role in immunity, is directly upregulated by inflammation. In this study, we analyzed whether inflammation is also a modulator of TMPRSS6 expression in vitro and in vivo and we determined the mechanism of this regulation A Human Hepatoma cell line was treated with interleukin-6 and mice were injected with lipopolysaccharide and TMPRSS6 expression and the regulatory mechanism were addressed. In this study, we demonstrate that inflammation downregulates TMPRSS6 expression in vitro and in vivo. The downregulation of Tmprss6 by inflammation in mice is not dependent on the Bmp-Smad pathway but occurs through a decrease in Stat5 phosphorylation. Moreover, Stat5 positively regulates Tmprss6 expression directly by binding to a Stat5 element located on the Tmprss6 promoter. Importantly, our results highlight the functional role of inflammatory modulation of TMPRSS6 expression in the regulation of hepcidin. TMPRSS6 inhibition via decreased STAT5 phosphorylation may be an additional mechanism by which inflammation stimulates hepcidin expression to regulate iron homeostasis and immunity. C1 [Meynard, Delphine; Sun, Chia Chi; Wu, Qifang; Chen, Wenjie; Chen, Shanzhuo; Babitt, Jodie L.; Lin, Herbert Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Program Membrane Biol, Program Anemia Signaling Res,Div Nephrol,Ctr Syst, Boston, MA 02115 USA. [Nelson, Caroline N.; Waters, Michael J.] Univ Queensland, Inst Mol Biosci, St Lucia, Qld, Australia. RP Meynard, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Program Membrane Biol, Program Anemia Signaling Res,Div Nephrol,Ctr Syst, Boston, MA 02115 USA. EM meynard-sautet.delphine@mgh.harvard.edu; Lin.Herbert@mgh.harvard.edu RI meynard, delphine/B-4236-2014; waters, michael/C-9582-2014 FU MGH Fund for Medical Discovery; National Institutes of Health (NIH) [RO1 DK087727]; Massachusetts General Hospital; NIH [RO1 DK-069533, RO1 DK-071837] FX DM was supported by a Postdoctoral Fellowship Award from the MGH Fund for Medical Discovery, JLB was supported in part by National Institutes of Health (NIH) grant RO1 DK087727, and by Claflin Distinguished Scholar and Howard Goodman Fellowship Awards from the Massachusetts General Hospital. HYL was supported in part by NIH grants RO1 DK-069533 and RO1 DK-071837. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 27 TC 4 Z9 4 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 23 PY 2013 VL 8 IS 12 AR e82127 DI 10.1371/journal.pone.0082127 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 278IG UT WOS:000328882000007 PM 24376517 ER PT J AU Chirieac, LR Barletta, JA Yeap, BY Richards, WG Tilleman, T Bueno, R Baldini, EH Godleski, J Sugarbaker, DJ AF Chirieac, Lucian R. Barletta, Justine A. Yeap, Beow Y. Richards, William G. Tilleman, Tamara Bueno, Raphael Baldini, Elizabeth H. Godleski, John Sugarbaker, David J. TI Clinicopathologic Characteristics of Malignant Mesotheliomas Arising in Patients With a History of Radiation for Hodgkin and Non-Hodgkin Lymphoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PLEURAL MESOTHELIOMA; ASBESTOS; SURVIVAL; THERAPY AB Purpose Studies have reported an association between pleural diffuse malignant mesothelioma (PDMM) and chest radiation for lymphoma. The clinicopathologic characteristics of malignant mesotheliomas arising in these patients have not been established. Patients and Methods We studied 1,618 consecutive patients diagnosed with pleural PDMM from July 1993 to February 2008 and identified patients with a history of radiation for Hodgkin and non-Hodgkin lymphoma. We evaluated the histology in the surgical resection specimens and compared clinicopathologic features with overall survival. Results We identified 22 patients who developed PDMM after chest radiation as part of their treatment for lymphoma (mean latency time, 21.4 years; 95% CI, 17.0 to 25.8 years). Asbestos bodies in lymphoma-associated PDMM were lower than in asbestos-associated PDMM (median count, 15 v 325 bodies, respectively; P < .001) and similar to an unexposed control group (median count, 15 v 10 bodies, respectively; P = .6). Seventeen lymphoma-associated PDMMs (77%) were epithelioid and five (23%) were biphasic. Seven PDMMs (32%) had unusual histologies (pleomorphic, myxoid, clear cell, and signet ring cell). Patients with lymphoma-associated PDMM were younger than patients with asbestos-associated PDMM (median age, 45 v 64 years, respectively; P < .001) and had a significantly longer overall survival time (median, 32.5 v 12.7 months, respectively; P = .018). In multivariate analysis, independent favorable predictors for overall survival were history of prior radiation (P = .022), female sex (P < .001), age 65 years (P = .005), cytoreductive surgery (P < .001), and epithelioid histology (P < .001). Conclusion Patients with lymphoma-associated PDMM are likely to have unusual histologic features, are significantly younger, and seem to have a longer overall survival compared with patients with asbestos-associated PDMM. C1 [Chirieac, Lucian R.; Barletta, Justine A.; Richards, William G.; Tilleman, Tamara; Bueno, Raphael; Baldini, Elizabeth H.; Godleski, John; Sugarbaker, David J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Yeap, Beow Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Richards, William G.; Tilleman, Tamara; Bueno, Raphael; Baldini, Elizabeth H.; Sugarbaker, David J.] Harvard Univ, Sch Med, Boston, MA USA. RP Chirieac, LR (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM lchirieac@partners.org FU International Mesothelioma Program FX Supported by the International Mesothelioma Program. NR 26 TC 8 Z9 8 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 20 PY 2013 VL 31 IS 36 BP 4544 EP + DI 10.1200/JCO.2013.49.9616 PG 8 WC Oncology SC Oncology GA 282QG UT WOS:000329186700011 PM 24248693 ER PT J AU Frank, DA AF Frank, David A. TI Transcription Factor STAT3 As a Prognostic Marker and Therapeutic Target in Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SIGNAL TRANSDUCER; BREAST-CANCER; HUMAN TUMORS; ACTIVATOR; PROTEINS; PATHWAY; PHOSPHORYLATION; IDENTIFICATION; BCR/ABL; GROWTH C1 [Frank, David A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Frank, David A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Frank, David A.] Harvard Univ, Sch Med, Boston, MA USA. RP Frank, DA (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM david_frank@dfci.harvard.edu NR 24 TC 10 Z9 10 U1 1 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 20 PY 2013 VL 31 IS 36 BP 4560 EP 4561 DI 10.1200/JCO.2013.52.8414 PG 2 WC Oncology SC Oncology GA 282QG UT WOS:000329186700013 PM 24220556 ER PT J AU Hughes, KS Schnaper, LA Bellon, JR Cirrincione, CT Berry, DA McCormick, B Muss, HB Smith, BL Hudis, CA Winer, EP Wood, WC AF Hughes, Kevin S. Schnaper, Lauren A. Bellon, Jennifer R. Cirrincione, Constance T. Berry, Donald A. McCormick, Beryl Muss, Hyman B. Smith, Barbara L. Hudis, Clifford A. Winer, Eric P. Wood, William C. TI Radiotherapy for Elderly Patients With Breast Cancer Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID RANDOMIZED-TRIALS C1 [Hughes, Kevin S.; Smith, Barbara L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Schnaper, Lauren A.] Greater Baltimore Med Ctr, Baltimore, MD USA. [Bellon, Jennifer R.; Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cirrincione, Constance T.] Duke Univ, Alliance Canc & Leukemia Grp B, Stat & Data Ctr, Durham, NC USA. [Berry, Donald A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [McCormick, Beryl; Hudis, Clifford A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Muss, Hyman B.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Wood, William C.] Emory Univ, Sch Med, Atlanta, GA USA. RP Hughes, KS (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. OI Hughes, Kevin/0000-0003-4084-6484 NR 7 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 20 PY 2013 VL 31 IS 36 BP 4571 EP 4573 DI 10.1200/JCO.2013.52.8943 PG 3 WC Oncology SC Oncology GA 282QG UT WOS:000329186700018 PM 24190113 ER PT J AU Vafai, SB Mootha, VK AF Vafai, Scott B. Mootha, Vamsi K. TI A Common Pathway for a Rare Disease? SO SCIENCE LA English DT Editorial Material C1 [Vafai, Scott B.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. [Vafai, Scott B.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Med, Howard Hughes Med Inst, Boston, MA 02114 USA. [Vafai, Scott B.; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Vafai, Scott B.; Mootha, Vamsi K.] Broad Inst, Boston, MA 02141 USA. RP Vafai, SB (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. EM vamsi@hms.harvard.edu FU Howard Hughes Medical Institute NR 11 TC 10 Z9 10 U1 1 U2 10 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD DEC 20 PY 2013 VL 342 IS 6165 BP 1453 EP 1454 DI 10.1126/science.1248449 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 274ZI UT WOS:000328644300037 PM 24357304 ER PT J AU Julien, JP Cupo, A Sok, D Stanfield, RL Lyumkis, D Deller, MC Klasse, PJ Burton, DR Sanders, RW Moore, JP Ward, AB Wilson, IA AF Julien, Jean-Philippe Cupo, Albert Sok, Devin Stanfield, Robyn L. Lyumkis, Dmitry Deller, Marc C. Klasse, Per-Johan Burton, Dennis R. Sanders, Rogier W. Moore, John P. Ward, Andrew B. Wilson, Ian A. TI Crystal Structure of a Soluble Cleaved HIV-1 Envelope Trimer SO SCIENCE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NEUTRALIZING ANTIBODY PG9; N-GLYCAN RECOGNITION; GLYCOPROTEIN TRIMER; VARIABLE LOOPS; MOLECULAR ARCHITECTURE; POTENT NEUTRALIZATION; MEMBRANE-FUSION; GP120 CORE; V3 LOOP AB HIV-1 entry into CD4(+) target cells is mediated by cleaved envelope glycoprotein (Env) trimers that have been challenging to characterize structurally. Here, we describe the crystal structure at 4.7 angstroms of a soluble, cleaved Env trimer that is stabilized and antigenically near-native (termed the BG505 SOSIP. 664 gp140 trimer) in complex with a potent broadly neutralizing antibody, PGT122. The structure shows a prefusion state of gp41, the interaction between the component gp120 and gp41 subunits, and how a close association between the gp120 V1/V2/V3 loops stabilizes the trimer apex around the threefold axis. The complete epitope of PGT122 on the trimer involves gp120 V1, V3, and several surrounding glycans. This trimer structure advances our understanding of how Env functions and is presented to the immune system, and provides a blueprint for structure-based vaccine design. C1 [Julien, Jean-Philippe; Stanfield, Robyn L.; Lyumkis, Dmitry; Ward, Andrew B.; Wilson, Ian A.] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA. [Julien, Jean-Philippe; Sok, Devin; Stanfield, Robyn L.; Burton, Dennis R.; Ward, Andrew B.; Wilson, Ian A.] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA. [Julien, Jean-Philippe; Sok, Devin; Stanfield, Robyn L.; Burton, Dennis R.; Ward, Andrew B.; Wilson, Ian A.] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA. [Cupo, Albert; Klasse, Per-Johan; Sanders, Rogier W.; Moore, John P.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Sok, Devin; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Lyumkis, Dmitry] Scripps Res Inst, Natl Resource Automated Mol Microscopy, La Jolla, CA 92037 USA. [Deller, Marc C.; Wilson, Ian A.] Scripps Res Inst, Joint Ctr Struct Genom, La Jolla, CA 92037 USA. [Burton, Dennis R.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA 02129 USA. [Sanders, Rogier W.] Univ Amsterdam, Acad Med Ctr, Dept Med Microbiol, NL-1105 AZ Amsterdam, Netherlands. [Wilson, Ian A.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. RP Moore, JP (reprint author), Cornell Univ, Weill Med Coll, New York, NY 10021 USA. EM jpm2003@med.cornell.edu; abward@scripps.edu; wilson@scripps.edu RI Ward, Andrew/F-9203-2014 OI Ward, Andrew/0000-0001-7153-3769 FU NIH [P01 AI82362, R01 AI084817, R37 AI36082, R01 AI33292]; International AIDS Vaccine Initiative Neutralizing Antibody Consortium and Center; CHAVI-ID [UM1 AI100663]; Netherlands Organization for Scientific Research; European Research Council; Canadian Institutes of Health Research fellowship; Ragon Institute; U.S. NIH National Institute of General Medical Sciences (NIGMS) Biomedical Technology Research Center program [GM103310]; NIH NIGMS via a Protein Structure Initiative [U54 GM094586]; U.S. Department of Energy (DOE), Basic Energy Sciences, Office of Science [DE-AC02-06CH11357]; National Cancer Institute (NCI) [Y1-CO-1020]; NIGMS [Y1-GM-1104]; DOE Office of Biological and Environmental Research; NIH's National Center for Research Resources, Biomedical Technology Program [P41RR001209]; NIGMS; Natural Sciences and Engineering Research Council of Canada; National Research Council Canada; Canadian Institutes of Health Research; Province of Saskatchewan; Western Economic Diversification Canada; University of Saskatchewan FX We thank Y. Hua, L. Kong, P. S. Lee, X. Zhu, R. Pejchal, H. Tien, T. Clayton, K. Saye, and J. Korzun, for technical assistance, previous contributions to the Env trimer project, and insightful discussions and C. R. King and W. Koff for support and encouragement. This work was supported by NIH grant P01 AI82362 (J. P. M., I. A. W.), as well as the International AIDS Vaccine Initiative Neutralizing Antibody Consortium and Center (D. R. B., I. A. W., J. P. M., A. B. W.), CHAVI-ID UM1 AI100663 (D. R. B., I. A. W., AB. W.), NIH grant R01 AI084817 (I. A. W.), NIH grant R37 AI36082 (J. P. M.), NIH grant R01 AI33292 (D. R. B.), a Vidi grant from the Netherlands Organization for Scientific Research (R. W. S.), a Starting Investigator Grant from the European Research Council (R. W. S.), Canadian Institutes of Health Research fellowship (J.-P.J.), and the Ragon Institute. D. L. is supported by the U.S. NIH National Institute of General Medical Sciences (NIGMS) Biomedical Technology Research Center program (grant GM103310). The Joint Center of Structural Genomics is supported by NIH NIGMS via a Protein Structure Initiative grant U54 GM094586 (I. A. W.). Use of the Advanced Photon Source for data collection was supported by the U.S. Department of Energy (DOE), Basic Energy Sciences, Office of Science, under contract no. DE-AC02-06CH11357. GM/CA CAT has been funded in whole or in part with federal funds from the National Cancer Institute (NCI) (grant Y1-CO-1020) and NIGMS (grant Y1-GM-1104). Extensive crystal screening was also carried out at the Stanford Synchrotron Radiation Lightsource (SSRL) and at the Canadian Light Source (CLS). SSRL, a Directorate of the SLAC National Accelerator Laboratory and an Office of Science User Facility, is operated for the U.S. DOE Office of Science by Stanford University. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research; NIH's National Center for Research Resources, Biomedical Technology Program (P41RR001209); and the NIGMS. CLS is supported by the Natural Sciences and Engineering Research Council of Canada, the National Research Council Canada, the Canadian Institutes of Health Research, the Province of Saskatchewan, Western Economic Diversification Canada, and the University of Saskatchewan. The content is the responsibility of the authors and does not necessarily reflect the official views of the NIGMS, NCI, or NIH. Coordinates and structure factors have been deposited with the Protein Data Bank under accession code 4NCO. The International AIDS Vaccine Initiative has previously filed a patent relating to the BG505 SOSIP. 664 trimer: U.S. Provisional Application no. 61/772,739, titled "HIV-1 envelope glycoprotein," with inventors M. Caulfield, A. C., H. Dean, S. Hoffenberg, C. R. King, P. J. K., A. Marozsan, J. P. M., R. S., A. B. W., I. A. W., J.-P. J., but no patents have been filed on any work described here. Materials and information will be provided under a Materials Transfer Agreement. This is manuscript 25054 from The Scripps Research Institute. NR 56 TC 333 Z9 335 U1 18 U2 95 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD DEC 20 PY 2013 VL 342 IS 6165 BP 1477 EP 1483 DI 10.1126/science.1245625 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 274ZI UT WOS:000328644300050 PM 24179159 ER PT J AU Bhushan, A Senutovitch, N Bale, SS McCarty, WJ Hegde, M Jindal, R Golberg, I Usta, OB Yarmush, ML Vernetti, L Gough, A Bakan, A Shun, TY DeBiasio, R Taylor, DL AF Bhushan, Abhinav Senutovitch, Nina Bale, Shyam S. McCarty, William J. Hegde, Manjunath Jindal, Rohit Golberg, Inna Usta, O. Berk Yarmush, Martin L. Vernetti, Lawrence Gough, Albert Bakan, Ahmet Shun, Tong Ying DeBiasio, Richard Taylor, D. Lansing TI Towards a three-dimensional microfluidic liver platform for predicting drug efficacy and toxicity in humans SO STEM CELL RESEARCH & THERAPY LA English DT Review ID ENDOTHELIAL-CELLS; HEPATOCYTE; INJURY; MECHANISMS; COCULTURES; HEPATOTOXICITY; BIOSENSORS; ANIMALS; CULTURE; VEGF AB Although the process of drug development requires efficacy and toxicity testing in animals prior to human testing, animal models have limited ability to accurately predict human responses to xenobiotics and other insults. Societal pressures are also focusing on reduction of and, ultimately, replacement of animal testing. However, a variety of in vitro models, explored over the last decade, have not been powerful enough to replace animal models. New initiatives sponsored by several US federal agencies seek to address this problem by funding the development of physiologically relevant human organ models on microscopic chips. The eventual goal is to simulate a human-on-a-chip, by interconnecting the organ models, thereby replacing animal testing in drug discovery and development. As part of this initiative, we aim to build a three-dimensional human liver chip that mimics the acinus, the smallest functional unit of the liver, including its oxygen gradient. Our liver-on-a-chip platform will deliver a microfluidic three-dimensional co-culture environment with stable synthetic and enzymatic function for at least 4 weeks. Sentinel cells that contain fluorescent biosensors will be integrated into the chip to provide multiplexed, real-time readouts of key liver functions and pathology. We are also developing a database to manage experimental data and harness external information to interpret the multimodal data and create a predictive platform. C1 [Bhushan, Abhinav; Senutovitch, Nina; Bale, Shyam S.; McCarty, William J.; Hegde, Manjunath; Jindal, Rohit; Golberg, Inna; Usta, O. Berk; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Shriners Hosp Children Boston,Ctr Engn Med, Boston, MA 02114 USA. [Senutovitch, Nina; Vernetti, Lawrence; Gough, Albert; Shun, Tong Ying; DeBiasio, Richard; Taylor, D. Lansing] Univ Pittsburgh, Drug Discovery Inst, Pittsburgh, PA 15260 USA. [Senutovitch, Nina; Vernetti, Lawrence; Gough, Albert; Bakan, Ahmet; Taylor, D. Lansing] Univ Pittsburgh, Dept Computat & Syst Biol, Pittsburgh, PA 15260 USA. RP Senutovitch, N (reprint author), Univ Pittsburgh, Drug Discovery Inst, 10040 Biomed Sci Tower 3,3501 5th Ave, Pittsburgh, PA 15260 USA. EM ninas@pitt.edu RI Hegde, Manjunath/M-3038-2014; USTA, O. Berk/A-5818-2008; OI Hegde, Manjunath/0000-0002-5396-2241; USTA, O. Berk/0000-0001-9328-568X; Gough, Albert/0000-0001-6456-0195; McCarty, William/0000-0002-3671-0616 FU National Institutes of Health Common Fund [1UH2TR000503]; National Institutes of Health, National Center for Advancing Translations Science [5UH2TR000503-02] FX This work was supported in part by the National Institutes of Health Common Fund 1UH2TR000503 (to DLT and MLY, co-principal investigators). Publication costs are funded by the National Institutes of Health, National Center for Advancing Translations Science under grant 5UH2TR000503-02 to DLT. NR 33 TC 14 Z9 16 U1 4 U2 50 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1757-6512 J9 STEM CELL RES THER JI Stem Cell Res. Ther. PD DEC 20 PY 2013 VL 4 SU 1 AR S16 DI 10.1186/scrt377 PG 6 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 286DG UT WOS:000329444700017 PM 24565476 ER PT J AU Wheeler, SE Borenstein, JT Clark, AM Ebrahimkhani, M Fox, IJ Griffith, L Inman, W Lauffenburger, D Nguyen, T Pillai, VC Prantil-Baun, R Stolz, DB Taylor, D Ulrich, T Venkataramanan, R Wells, A Young, C AF Wheeler, Sarah E. Borenstein, Jeffrey T. Clark, Amanda M. Ebrahimkhani, Mohammed Fox, Ira J. Griffith, Linda Inman, Walker Lauffenburger, Douglas Transon Nguyen Pillai, Venkateswaran C. Prantil-Baun, Rachelle Stolz, Donna B. Taylor, Donald Ulrich, Theresa Venkataramanan, Raman Wells, Alan Young, Carissa TI All-human microphysical model of metastasis therapy SO STEM CELL RESEARCH & THERAPY LA English DT Review DE liver; mammary carcinoma; microenvironment; tumor dissemination ID SYSTEMS BIOLOGY; CIRCADIAN CLOCK; DORMANCY; CANCER; MORPHOGENESIS; INEFFICIENCY; PROGRESSION; SURVIVAL; CULTURES; RHYTHMS AB The vast majority of cancer mortalities result from distant metastases. The metastatic microenvironment provides unique protection to ectopic tumors as the primary tumors often respond to specific agents. Although significant interventional progress has been made on primary tumors, the lack of relevant accessible model in vitro systems in which to study metastases has plagued metastatic therapeutic development - particularly among micrometastases. A real-time, all-human model of metastatic seeding and cancer cells that recapitulate metastatic growth and can be probed in real time by a variety of measures and challenges would provide a critical window into the pathophysiology of metastasis and pharmacology of metastatic tumor resistance. To achieve this we are advancing our microscale bioreactor that incorporates human hepatocytes, human nonparenchymal liver cells, and human breast cancer cells to mimic the hepatic niche in three dimensions with functional tissue. This bioreactor is instrumented with oxygen sensors, micropumps capable of generating diurnally varying profiles of nutrients and hormones, while enabling real-time sampling. Since the liver is a major metastatic site for a wide variety of carcinomas and other tumors, this bioreactor uniquely allows us to more accurately recreate the human metastatic microenvironment and probe the paracrine effects between the liver parenchyma and metastatic cells. Further, as the liver is the principal site of xenobiotic metabolism, this reactor will help us investigate the chemotherapeutic response within a metabolically challenged liver microenvironment. This model is anticipated to yield markers of metastatic behavior and pharmacologic metabolism that will enable better clinical monitoring, and will guide the design of clinical studies to understand drug efficacy and safety in cancer therapeutics. This highly instrumented bioreactor format, hosting a growing tumor within a microenvironment and monitoring its responses, is readily transferable to other organs, giving this work impact beyond the liver. C1 [Wheeler, Sarah E.; Clark, Amanda M.; Taylor, Donald; Wells, Alan] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15261 USA. [Borenstein, Jeffrey T.; Transon Nguyen; Prantil-Baun, Rachelle] Charles Stark Draper Lab, Cambridge, MA 02139 USA. [Ebrahimkhani, Mohammed; Griffith, Linda; Inman, Walker; Lauffenburger, Douglas; Ulrich, Theresa; Young, Carissa] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Fox, Ira J.; Wells, Alan] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA 15203 USA. [Pillai, Venkateswaran C.; Venkataramanan, Raman] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. [Stolz, Donna B.] Univ Pittsburgh, Dept Surg, Dept Cell Biol, Pittsburgh, PA 15261 USA. [Taylor, Donald; Wells, Alan] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15219 USA. [Wells, Alan] VA Pittsburgh Healthcare Syst, Pittsburg VA Med Ctr, Pittsburgh, PA 15240 USA. RP Wells, A (reprint author), Univ Pittsburgh, Dept Pathol, 3550 Terrace St,S713 Scaife Hall, Pittsburgh, PA 15261 USA. EM wellsa@upmc.edu OI Clark, Amanda/0000-0003-1590-2560; Wells, Alan/0000-0002-1637-8150 FU NIH [1UH2TR000496-01, DARPA-BAA-11-73] FX Funding for publication of this article came from grants NIH 1UH2TR000496-01 (All-human Microphysical Model of Metastasis Therapy) and DARPA-BAA-11-73 (Microphysiological Systems: W911NF-12-2-0039 Barrier-Immune-Organ: Microphysiology, Microenvironment Engineered Tissue Construct Systems (BIO-MIMETICS)). NR 30 TC 10 Z9 10 U1 3 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1757-6512 J9 STEM CELL RES THER JI Stem Cell Res. Ther. PD DEC 20 PY 2013 VL 4 SU 1 AR S11 DI 10.1186/scrt372 PG 5 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 286DG UT WOS:000329444700012 PM 24565274 ER PT J AU Ranayhossaini, DJ Rodriguez, AI Sahoo, S Chen, BB Mallampalli, RK Kelley, EE Csanyi, G Gladwin, MT Romero, G Pagano, PJ AF Ranayhossaini, Daniel J. Rodriguez, Andres I. Sahoo, Sanghamitra Chen, Beibei B. Mallampalli, Rama K. Kelley, Eric E. Csanyi, Gabor Gladwin, Mark T. Romero, Guillermo Pagano, Patrick J. TI Selective Recapitulation of Conserved and Nonconserved Regions of Putative NOXA1 Protein Activation Domain Confers Isoform-specific Inhibition of Nox1 Oxidase and Attenuation of Endothelial Cell Migration SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Enzyme Inhibitors; Enzyme Mechanisms; NADPH Oxidase; Peptides; Reactive Oxygen Species (ROS); Nox1 ID NADPH OXIDASE; HYDROGEN-PEROXIDE; SUPEROXIDE GENERATION; NITRIC-OXIDE; OXYGEN; PEPTIDE; PEROXYNITRITE; HYPERTENSION; P67(PHOX); DIPHENYLENEIODONIUM AB Background: Nox1, an oxidant source in colon carcinoma and vascular disease, is activated by NOXA1. Results: A NOXA1 peptide blocked NOXA1-Nox1 binding and inhibited colon carcinoma and endothelial oxidants and migration. Conclusion: The findings identify a NOXA1-activating domain and an isoform-specific Nox1 inhibitor. Significance: The data provide insight into Nox1 regulation and present a potential therapy for suppressing oxidative stress-related disease. Excessive vascular and colon epithelial reactive oxygen species production by NADPH oxidase isoform 1 (Nox1) has been implicated in a number of disease states, including hypertension, atherosclerosis, and neoplasia. A peptide that mimics a putative activation domain of the Nox1 activator subunit NOXA1 (NOXA1 docking sequence, also known as NoxA1ds) potently inhibited Nox1-derived superoxide anion (O-radical anion) production in a reconstituted Nox1 cell-free system, with no effect on Nox2-, Nox4-, Nox5-, or xanthine oxidase-derived reactive oxygen species production as measured by cytochrome c reduction, Amplex Red fluorescence, and electron paramagnetic resonance. The ability of NoxA1ds to cross the plasma membrane was tested by confocal microscopy in a human colon cancer cell line exclusively expressing Nox1 (HT-29) using FITC-labeled NoxA1ds. NoxA1ds significantly inhibited whole HT-29 carcinoma cell-derived O-radical anion generation. ELISA and fluorescence recovery after photobleaching experiments indicate that NoxA1ds, but not its scrambled control, binds Nox1. FRET experiments conducted using Nox1-YFP and NOXA1-CFP illustrate that NoxA1ds disrupts the binding interaction between Nox1 and NOXA1, whereas a control peptide did not. Moreover, hypoxia-induced human pulmonary artery endothelial cell O-radical anion production was completely inhibited by NoxA1ds. Human pulmonary artery endothelial cell migration under hypoxic conditions was also reduced by pretreatment with NoxA1ds. Our data indicate that a peptide recapitulating a putative activation subdomain of NOXA1 (NoxA1ds) is a highly efficacious and selective inhibitor of Nox1 activity and establishes a critical interaction site for Nox1-NOXA1 binding required for enzyme activation. C1 [Ranayhossaini, Daniel J.; Rodriguez, Andres I.; Kelley, Eric E.; Csanyi, Gabor; Gladwin, Mark T.; Pagano, Patrick J.] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA 15261 USA. [Ranayhossaini, Daniel J.; Rodriguez, Andres I.; Sahoo, Sanghamitra; Kelley, Eric E.; Csanyi, Gabor; Romero, Guillermo; Pagano, Patrick J.] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15261 USA. [Chen, Beibei B.; Mallampalli, Rama K.; Gladwin, Mark T.] Univ Pittsburgh, Dept Pulm Allergy & Crit Care Med, Pittsburgh, PA 15261 USA. [Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA 15240 USA. RP Pagano, PJ (reprint author), Univ Pittsburgh, BST E1247,200 Lothrop St, Pittsburgh, PA 15261 USA. EM pagano@pitt.edu FU National Institutes of Health [HL079207, HL096376, HL097376, HL098174, HL116472]; United States Department of Veterans Affairs FX This work was supported, in whole or in part, by National Institutes of Health Grant HL079207; Grants HL096376, HL097376, and HL098174 (to R. K. M.); and Grant HL116472 (to B. B. C.). This work was also supported by a merit review award from the United States Department of Veterans Affairs. This work is the subject of a pending United States patent application No. 61/560,075 titled "Novel Inhibitors of Nox1," on which D. J. R. and P. J. P. are listed as inventors. NR 57 TC 14 Z9 15 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 20 PY 2013 VL 288 IS 51 BP 36437 EP 36450 DI 10.1074/jbc.M113.521344 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 278IQ UT WOS:000328883400025 PM 24187133 ER PT J AU Troeger, A Chae, HD Senturk, M Wood, J Williams, DA AF Troeger, Anja Chae, Hee-Don Senturk, Mumine Wood, Jenna Williams, David A. TI A Unique Carboxyl-terminal Insert Domain in the Hematopoietic-specific, GTPase-deficient Rho GTPase RhoH Regulates Post-translational Processing SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Autophagy; Protein Degradation; Protein Stability; Rho GTPases; T Cell; Atypical Rho GTPases; B-Cell Malignancies; RhoH; Carboxyl Terminus; Chaperone-mediated Autophagy ID ABERRANT SOMATIC HYPERMUTATION; CHRONIC LYMPHOCYTIC-LEUKEMIA; T-CELL-RECEPTOR; PROTEIN-DEGRADATION; PROGENITOR CELLS; BINDING PROTEIN; GENE-TRANSFER; AUTOPHAGY; UBIQUITIN; EXPRESSION AB Background: RhoH is required for T cell development and non-coding RhoH mutations are found in B-cell lymphoma. Results: The C-terminal insert domain regulates RhoH protein stability via chaperone-mediated autophagy. Conclusion: Although the insert domain is required for lysosomal uptake, it is dispensable for T cell development. Significance: Targeting the insert domain may permit alteration of RhoH protein levels without impairing vital protein functions. RhoH is a hematopoietic-specific, GTPase-deficient member of the Rho GTPase family that was first identified as a hypermutable gene in human B lineage lymphomas. RhoH remains in a constitutively active state and thus its effects are regulated by expression levels or post-translational modifications. Similar to other small GTPases, intracellular localization of RhoH is dependent upon the conserved CAAX box and surrounding sequences within the carboxyl (C) terminus. However, RhoH also contains a unique C-terminal insert domain of yet undetermined function. RhoH serves as adaptor molecule in T cell receptor signaling and RhoH expression correlates with the unfavorable prognostic marker ZAP70 in human chronic lymphocytic leukemia. Disease progression is attenuated in a Rhoh(-/-) mouse model of chronic lymphocytic leukemia and treatment of primary human chronic lymphocytic leukemia cells with Lenalidomide results in reduced RhoH protein levels. Thus, RhoH is a potential therapeutic target in B cell malignancies. In the current studies, we demonstrate that deletion of the insert domain (LFSINE) results in significant cytoplasmic protein accumulation. Using inhibitors of degradation pathways, we show that LFSINE regulates lysosomal RhoH uptake and degradation via chaperone-mediated autophagy. Whereas the C-terminal prenylation site is critical for ZAP70 interaction, subcellular localization and rescue of the Rhoh(-/-) T cell defect in vivo, the insert domain appears dispensable for these functions. Taken together, our findings suggest that the insert domain regulates protein stability and activity without otherwise affecting RhoH function. C1 [Troeger, Anja; Wood, Jenna; Williams, David A.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Troeger, Anja; Wood, Jenna; Williams, David A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chae, Hee-Don] Stanford Univ, Sch Med, Div Hematol Oncol, Dept Pediat,CSCR 1210, Stanford, CA 94305 USA. [Senturk, Mumine] Baylor Coll Med, Dept Dev Biol, Houston, TX 77030 USA. [Troeger, Anja] Univ Dusseldorf, Clin Pediat Oncol Hematol & Clin Immunol, D-40225 Dusseldorf, Germany. RP Williams, DA (reprint author), Karp Family Res Labs 08125 3, 300 Longwood Ave, Boston, MA 02115 USA. EM DAWilliams@childrens.harvard.edu RI Chae, Hee-Don/D-2620-2011 FU National Institutes of Health [CA113969]; Deutsche Forschungsgemeinschaft [TR 1005/1-1] FX This work was supported, in whole or in part, by National Institutes of Health Grant CA113969 (to D. A. W.) and Deutsche Forschungsgemeinschaft Grant TR 1005/1-1 (to A. T.). NR 57 TC 2 Z9 2 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 20 PY 2013 VL 288 IS 51 BP 36451 EP 36462 DI 10.1074/jbc.M113.505727 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 278IQ UT WOS:000328883400026 PM 24189071 ER PT J AU Kistler, AD Singh, G Altintas, MM Yu, H Fernandez, IC Gu, CK Wilson, C Srivastava, SK Dietrich, A Walz, K Kerjaschki, D Ruiz, P Dryer, S Sever, S Dinda, AK Faul, C Reiser, J AF Kistler, Andreas D. Singh, Geetika Altintas, Mehmet M. Yu, Hao Fernandez, Isabel C. Gu, Changkyu Wilson, Cory Srivastava, Sandeep Kumar Dietrich, Alexander Walz, Katherina Kerjaschki, Dontscho Ruiz, Phillip Dryer, Stuart Sever, Sanja Dinda, Amit K. Faul, Christian Reiser, Jochen TI Transient Receptor Potential Channel 6 (TRPC6) Protects Podocytes during Complement-mediated Glomerular Disease SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Calcium Signaling; CaMKII; Complement; Kidney; Podocytes; TRP Channels; TRPC6; Membranous Nephropathy; Nephrotoxic Serum Nephritis ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; NEPHROTOXIC SERUM NEPHRITIS; DECAY-ACCELERATING FACTOR; MEMBRANOUS NEPHROPATHY; ACTIN CYTOSKELETON; EPITHELIAL-CELLS; SLIT DIAPHRAGM; INJURY; MICE; DIACYLGLYCEROL AB Background: Activating mutations of the calcium channel TRPC6 lead to adult onset genetic kidney disease. Results: In acquired kidney diseases, increased TRPC6 expression protects kidney podocytes against complement-mediated injury. Conclusion: The effect, protective or nocuous, of TRPC6 in podocytes is context dependent. Significance: Pharmacologic inhibition of TRPC6 in acquired kidney disease may be detrimental. Gain-of-function mutations in the calcium channel TRPC6 lead to autosomal dominant focal segmental glomerulosclerosis and podocyte expression of TRPC6 is increased in some acquired human glomerular diseases, particularly in membranous nephropathy. These observations led to the hypothesis that TRPC6 overactivation is deleterious to podocytes through pathological calcium signaling, both in genetic and acquired diseases. Here, we show that the effects of TRPC6 on podocyte function are context-dependent. Overexpression of TRPC6 alone did not directly affect podocyte morphology and cytoskeletal structure. Unexpectedly, however, overexpression of TRPC6 protected podocytes from complement-mediated injury, whereas genetic or pharmacological TRPC6 inactivation increased podocyte susceptibility to complement. Mechanistically, this effect was mediated by Ca2+/calmodulin-dependent protein kinase II (CaMKII) activation. Podocyte-specific TRPC6 transgenic mice showed stronger CaMKII activation, reduced podocyte foot process effacement and reduced levels of proteinuria during nephrotoxic serum nephritis, whereas TRPC6 null mice exhibited reduced CaMKII activation and higher levels of proteinuria compared with wild type littermates. Human membranous nephropathy biopsy samples showed podocyte staining for active CaMKII, which correlated with the degree of TRPC6 expression. Together, these data suggest a dual and context dependent role of TRPC6 in podocytes where acute activation protects from complement-mediated damage, but chronic overactivation leads to focal segmental glomerulosclerosis. C1 [Kistler, Andreas D.; Yu, Hao; Faul, Christian] Univ Miami, Dept Med, Div Nephrol & Hypertens, Miller Sch Med, Miami, FL 33136 USA. [Kistler, Andreas D.] Univ Zurich Hosp, Div Nephrol, CH-8091 Zurich, Switzerland. [Singh, Geetika; Srivastava, Sandeep Kumar; Dinda, Amit K.] All India Inst Med Sci, Dept Pathol, New Delhi 110029, DL, India. [Altintas, Mehmet M.; Fernandez, Isabel C.; Reiser, Jochen] Rush Univ, Dept Med, Ctr Med, Chicago, IL 60612 USA. [Gu, Changkyu; Sever, Sanja] Harvard Univ, Sch Med, Dept Med, Nephrol Div, Charlestown, MA 02129 USA. [Gu, Changkyu; Sever, Sanja] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Wilson, Cory; Dryer, Stuart] Univ Houston, Dept Biol & Biochem, Houston, TX 77004 USA. [Dietrich, Alexander] Univ Munich, Walther Straub Inst Pharmacol & Toxicol, D-80336 Munich, Germany. [Walz, Katherina] Univ Miami, John P Hussman Inst Human Genom, Miller Sch Med, Miami, FL 33136 USA. [Kerjaschki, Dontscho] Med Univ Vienna, Clin Inst Pathol, A-1090 Vienna, Austria. [Ruiz, Phillip] Univ Miami, Dept Surg, Miami, FL 33136 USA. RP Kistler, AD (reprint author), Rush Univ, Dept Med, Ctr Med, 1735 W Harrison St,Cohn Res Bldg,Ste 724, Chicago, IL 60612 USA. EM jochen_reiser@rush.edu OI Wilson, Cory/0000-0003-3948-3831; Dietrich, Alexander/0000-0002-1168-8707; Altintas, Mehmet/0000-0002-1871-6985 FU National Institutes of Health [DK073495, DK089394, DK101350]; Swiss National Science Foundation; Swiss Society for Medical and Biological Scholarships; Amgen-FROMO scholarship FX This work was supported in part by Grants DK073495, DK089394, and DK101350 from the National Institutes of Health (to J. R.).; Supported by a grant from the Swiss National Science Foundation, a grant from the Swiss Society for Medical and Biological Scholarships, and an Amgen-FROMO scholarship. To whom correspondence may be addressed: University Hospital Zurich, Ramistrasse 100, 8091 Zurich, Switzerland. Tel.: 41-44-255-13-89; Fax: 41-44-255-45-93. NR 51 TC 14 Z9 14 U1 0 U2 12 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 20 PY 2013 VL 288 IS 51 BP 36598 EP 36609 DI 10.1074/jbc.M113.488122 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 278IQ UT WOS:000328883400040 PM 24194522 ER PT J AU Gkotzamanidou, M Christoulas, D Souliotis, VL Papatheodorou, A Dimopoulos, MA Terpos, E AF Gkotzamanidou, Maria Christoulas, Dimitrios Souliotis, Vassilis L. Papatheodorou, Athanasios Dimopoulos, Meletios A. Terpos, Evangelos TI Angiogenic cytokines profile in smoldering multiple myeloma: No difference compared to MGUS but altered compared to symptomatic myeloma SO MEDICAL SCIENCE MONITOR LA English DT Article DE multiple myeloma; angiopoietins; angiogenin; VEGF; smoldering myeloma; angiogenesis ID BONE-MARROW ANGIOGENESIS; ENDOTHELIAL GROWTH-FACTOR; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; PROGNOSTIC-FACTOR; EXPRESSION; PROGRESSION; RECEPTORS; CELLS; ANGIOPOIETIN-2 AB Background: Symptomatic multiple myeloma (MM) evolves from an asymptomatic precursor state termed monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM). Angiogenesis plays a key role in the pathogenesis of MM but there are very limited data for angiogenesis in SMM. Material/Methods: We measured the circulating levels of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), and angiogenin in 54 patients with SMM. The results were compared with those of 27 MGUS patients, 55 MM patients, and 22 healthy controls. The expression of VEGF-A gene was also evaluated in 10 patients with SMM, 10 with symptomatic MM, and 10 with MGUS. Results: The ratio of circulating Ang-1/Ang-2 was reduced in MM patients with symptomatic disease due to a dramatic increase of Ang-2 (p<0.001), but not in patients with SMM or MGUS, in whom it did not differ compared to controls. VEGF and angiogenin were increased in all patients compared to controls. However, circulating VEGF was higher in symptomatic MM compared to SMM and MGUS, while angiogenin was reduced. There were no differences in the expression of VEGF-A among the 3 patients categories. Conclusions: SMM has a circulating angiogenic cytokine profile similar to that of MGUS, but has altered profile compared to symptomatic MM. Thus, in the progression of MGUS to SMM, circulating angiogenic cytokines seem to be the same. On the contrary, in symptomatic myeloma, the alterations of angiopoietins along with VEGF contribute to myeloma cell growth, supporting the target of these molecules for the development of novel anti-myeloma agents. C1 [Gkotzamanidou, Maria; Christoulas, Dimitrios; Dimopoulos, Meletios A.; Terpos, Evangelos] Univ Athens, Sch Med, Dept Clin Therapeut, Athens 11528, Greece. [Gkotzamanidou, Maria] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Souliotis, Vassilis L.] Natl Hellen Res Fdn, Inst Biol Med Chem & Biotechnol, Athens, Greece. [Papatheodorou, Athanasios] 21 Gen Air Force Hosp, Dept Med Res, Athens, Greece. RP Terpos, E (reprint author), Univ Athens, Sch Med, Dept Clin Therapeut, Athens 11528, Greece. EM eterpos@med.uoa.gr NR 29 TC 0 Z9 0 U1 0 U2 2 PU INT SCIENTIFIC LITERATURE, INC PI SMITHTOWN PA 361 FOREST LANE, SMITHTOWN, NY 11787 USA SN 1643-3750 J9 MED SCI MONITOR JI Med. Sci. Monitor PD DEC 20 PY 2013 VL 19 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 279HP UT WOS:000328951300001 ER PT J AU Mittal, S Wong, IY Yanik, AA Deen, WM Toner, M AF Mittal, Sukant Wong, Ian Y. Yanik, Ahmet Ali Deen, William M. Toner, Mehmet TI Discontinuous Nanoporous Membranes Reduce Non-Specific Fouling for Immunoaffinity Cell Capture SO SMALL LA English DT Article DE microfluidics; biosensors; nanoporous membranes; cell capture; non-specific adsorption ID CIRCULATING TUMOR-CELLS; ON-A-CHIP; MICROFLUIDIC DEVICES; EFFICIENT CAPTURE; FLOW; ADHESION; SYSTEMS; BLOOD; IMMOBILIZATION; ENRICHMENT AB The microfluidic isolation of target cells using adhesion-based surface capture has been widely explored for biology and medicine. However, high-throughput processing can be challenging due to interfacial limitations such as transport, reaction, and non-specific fouling. Here, it is shown that antibody-functionalized capture surfaces with discontinuous permeability enable efficient target cell capture at high flow rates by decreasing fouling. Experimental characterization and theoretical modeling reveal that wall effects affect cell-surface interactions and promote excess surface accumulation. These issues are partially circumvented by reducing the transport and deposition of cells near the channel walls. Optimized microfluidic devices can be operated at higher cell concentrations with significant improvements in throughput. C1 [Mittal, Sukant; Wong, Ian Y.; Yanik, Ahmet Ali; Toner, Mehmet] Massachusetts Gen Hosp, BioMEMS Resource Ctr, Ctr Engn Med, Charlestown, MA 02129 USA. [Mittal, Sukant; Wong, Ian Y.; Yanik, Ahmet Ali; Toner, Mehmet] Massachusetts Gen Hosp, Dept Surg, Charlestown, MA 02129 USA. [Mittal, Sukant; Wong, Ian Y.; Yanik, Ahmet Ali; Toner, Mehmet] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Deen, William M.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Mittal, Sukant; Toner, Mehmet] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Toner, M (reprint author), Massachusetts Gen Hosp, BioMEMS Resource Ctr, Ctr Engn Med, 114 16th St, Charlestown, MA 02129 USA. EM mehmet_toner@hms.harvard.edu RI Wong, Ian/G-1611-2012 OI Wong, Ian/0000-0002-9439-2548 FU National Institute of Biomedical Imaging and Bioengineering [P41-EB002503] FX S. Mittal and I. Y. Wong contributed equally to this work. We thank F. Fachin, O. Hurtado, E. Ozkumur and S. Stott for assistance with experiments and fabrication, as well as G. Chen, J. Martel and J. Voldman for insightful comments on the manuscript. This work was supported by the National Institute of Biomedical Imaging and Bioengineering under grant P41-EB002503 (BioMEMS Resource Center). I.Y.W. is the Merck Fellow of the Damon Runyon Cancer Research Foundation (DRG-2065-10). NR 47 TC 5 Z9 5 U1 6 U2 43 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1613-6810 EI 1613-6829 J9 SMALL JI Small PD DEC 20 PY 2013 VL 9 IS 24 BP 4207 EP 4214 DI 10.1002/smll.201300977 PG 8 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 272II UT WOS:000328453300015 PM 23766297 ER PT J AU Gilbert, GE AF Gilbert, Gary E. TI Factor VIII inhibitor epitopes and an enigma SO BLOOD LA English DT Editorial Material ID MEMBRANE-BINDING; C2 DOMAIN C1 [Gilbert, Gary E.] VA Boston Healthcare Syst, Boston, MA USA. [Gilbert, Gary E.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Gilbert, GE (reprint author), VA Boston Healthcare Syst, Boston, MA USA. NR 7 TC 2 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 19 PY 2013 VL 122 IS 26 BP 4160 EP 4161 DI 10.1182/blood-2013-10-531822 PG 4 WC Hematology SC Hematology GA 290FX UT WOS:000329741000007 PM 24357711 ER PT J AU Keo, HH Duval, S Baumgartner, I Oldenburg, NC Jaff, MR Goldman, J Peacock, JM Tretinyak, AS Henry, TD Luepker, RV Hirsch, AT AF Keo, Hong H. Duval, Sue Baumgartner, Iris Oldenburg, Niki C. Jaff, Michael R. Goldman, JoAnne Peacock, James M. Tretinyak, Alexander S. Henry, Timothy D. Luepker, Russell V. Hirsch, Alan T. TI The FReedom from Ischemic Events - New Dimensions for Survival (FRIENDS) registry: design of a prospective cohort study of patients with advanced peripheral artery disease SO BMC CARDIOVASCULAR DISORDERS LA English DT Article DE Peripheral artery disease; Amputation; Atherosclerosis; Health service research; Outcomes research ID LOWER-EXTREMITY; HEART-ASSOCIATION; VASCULAR-SURGERY; AMERICAN-COLLEGE; RANDOMIZED-TRIAL; MANAGEMENT; MULTICENTER; POPULATION; PREVENTION; GUIDELINES AB Background: Advanced lower extremity peripheral artery disease (PAD), whether presenting as acute limb ischemia (ALI) or chronic critical limb ischemia (CLI), is associated with high rates of cardiovascular ischemic events, amputation, and death. Past research has focused on strategies of revascularization, but few data are available that prospectively evaluate the impact of key process of care factors (spanning pre-admission, acute hospitalization, and post-discharge) that might contribute to improving short and long-term health outcomes. Methods/Design: The FRIENDS registry is designed to prospectively evaluate a range of patient and health system care delivery factors that might serve as future targets for efforts to improve limb and systemic outcomes for patients with ALI or CLI. This hypothesis-driven registry was designed to evaluate the contributions of: (i) pre-hospital limb ischemia symptom duration, (ii) use of leg revascularization strategies, and (iii) use of risk-reduction pharmacotherapies, as pre-specified factors that may affect amputation-free survival. Sequential patients would be included at an index "vascular specialist-defined" ALI or CLI episode, and patients excluded only for non-vascular etiologies of limb threat. Data including baseline demographics, functional status, co-morbidities, pre-hospital time segments, and use of medical therapies; hospital-based use of revascularization strategies, time segments, and pharmacotherapies; and rates of systemic ischemic events (e. g., myocardial infarction, stroke, hospitalization, and death) and limb ischemic events (e. g., hospitalization for revascularization or amputation) will be recorded during a minimum of one year follow-up. Discussion: The FRIENDS registry is designed to evaluate the potential impact of key factors that may contribute to adverse outcomes for patients with ALI or CLI. Definition of new "health system-based" therapeutic targets could then become the focus of future interventional clinical trials for individuals with advanced PAD. C1 [Keo, Hong H.] Kantonsspital Aarau AG, Div Angiol, Aarau, Switzerland. [Duval, Sue; Oldenburg, Niki C.; Hirsch, Alan T.] Univ Minnesota, Sch Med, Lillehei Heart Inst, Vasc Med Program, Minneapolis, MN 55455 USA. [Duval, Sue; Oldenburg, Niki C.; Hirsch, Alan T.] Univ Minnesota, Sch Med, Div Cardiovasc, Minneapolis, MN 55455 USA. [Baumgartner, Iris] Univ Hosp Bern, Div Angiol, Swiss Cardiovasc Ctr, CH-3010 Bern, Switzerland. [Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jaff, Michael R.] Harvard Univ, Sch Med, Boston, MA USA. [Goldman, JoAnne; Tretinyak, Alexander S.; Henry, Timothy D.] Abbott NW Hosp, Minneapolis Heart Inst Fdn, Minneapolis, MN 55407 USA. [Peacock, James M.] Minnesota Dept Hlth, Heart Dis & Stroke Prevent Unit, St Paul, MN USA. [Luepker, Russell V.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA. RP Hirsch, AT (reprint author), Univ Minnesota, Sch Med, Lillehei Heart Inst, Vasc Med Program, Minneapolis, MN 55455 USA. EM hirsc005@umn.edu FU Swiss National Science Foundation [PBBEB-121067]; Abbott Vascular, Switzerland; Abbott Vascular, USA FX Dr. Keo received a grant (PBBEB-121067) from the Swiss National Science Foundation and a research grant from Abbott Vascular, Switzerland. Dr. Hirsch received a grant from Abbott Vascular, USA, to support registry development. NR 33 TC 2 Z9 2 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2261 J9 BMC CARDIOVASC DISOR JI BMC Cardiovasc. Disord. PD DEC 19 PY 2013 VL 13 AR 120 DI 10.1186/1471-2261-13-120 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 292WN UT WOS:000329933500001 PM 24354507 ER PT J AU Dulcey, CE Dekimpe, V Fauvelle, DA Milot, S Groleau, MC Doucet, N Rahme, LG Lepine, F Deziel, E AF Dulcey, Carlos Eduardo Dekimpe, Valerie Fauvelle, David-Alexandre Milot, Sylvain Groleau, Marie-Christine Doucet, Nicolas Rahme, Laurence G. Lepine, Francois Deziel, Eric TI The End of an Old Hypothesis: The Pseudomonas Signaling Molecules 4-Hydroxy-2-Alkylquinolines Derive from Fatty Acids, Not 3-Ketofatty Acids SO CHEMISTRY & BIOLOGY LA English DT Article ID L-HOMOSERINE LACTONES; QUINOLONE SIGNAL; AERUGINOSA VIRULENCE; BIOSYNTHESIS; PATHOGENICITY; INTERFERENCE; PATHOGENESIS; GENES; 2,4-DIHYDROXYQUINOLINE; 2-AMINOACETOPHENONE AB Groups of pathogenic bacteria use diffusible signals to regulate their virulence in a concerted manner. Pseudomonas aeruginosa uses 4-hydroxy-2-alkylquinolines (HAQs), including 4-hydroxy-2-heptylquinoline (HHQ) and 3,4-dihydroxy-2-heptylquinoline (PQS), as unique signals. We demonstrate that octanoic acid is directly incorporated into HHQ. This finding rules out the long-standing hypothesis that 3-ketofatty acids are the precursors of HAQs. We found that HAQ biosynthesis, which requires the PqsABCD enzymes, proceeds by a two-step pathway: (1) PqsD mediates the synthesis of 2aminobenzoylacetate (2-ABA) from anthraniloylcoenzyme A (CoA) and malonyl-CoA, then (2) the decarboxylating coupling of 2-ABA to an octanoate group linked to PqsC produces HHQ, the direct precursor of PQS. PqsB is tightly associated with PqsC and required for the second step. This finding uncovers promising targets for the development of specific antivirulence drugs to combat this opportunistic pathogen. C1 [Dulcey, Carlos Eduardo; Dekimpe, Valerie; Fauvelle, David-Alexandre; Milot, Sylvain; Groleau, Marie-Christine; Doucet, Nicolas; Lepine, Francois; Deziel, Eric] Univ Quebec, INRS Inst Armand Frappier, Laval, PQ H7V 1B7, Canada. [Rahme, Laurence G.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lepine, F (reprint author), Univ Quebec, INRS Inst Armand Frappier, 531 Blvd Prairies, Laval, PQ H7V 1B7, Canada. EM francois.lepine@iaf.inrs.ca; eric.deziel@iaf.inrs.ca RI Deziel, Eric/A-7678-2008; OI Deziel, Eric/0000-0002-4609-0115; Groleau, Marie-Christine/0000-0003-4810-1030 FU Canadian Institutes of Health [MOP-97888]; National Sciences and Engineering Research Council of Canada; National Institutes of Health [2R56A1063433-06A1]; Fondation Armand-Frappier; Chercheur-boursier Junior 2 of the Fonds de la Recherche en Sante du Quebec and holds a Canada Research Chair in Sociomicrobiology FX Thanks to Melissa Starkey for providing plasmid pMSR1. This study was supported by Canadian Institutes of Health Research operating grant MOP-97888 to E.D., a National Sciences and Engineering Research Council of Canada Discovery grant to FL., and National Institutes of Health grant 2R56A1063433-06A1 to L.G.R. Respectively, C.E.D. and V.D. were recipients of an MSc and a PhD scholarship from the Fondation Armand-Frappier. E.D. was a Chercheur-boursier Junior 2 of the Fonds de la Recherche en Sante du Quebec and holds a Canada Research Chair in Sociomicrobiology. NR 49 TC 33 Z9 33 U1 0 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-5521 EI 1879-1301 J9 CHEM BIOL JI Chem. Biol. PD DEC 19 PY 2013 VL 20 IS 12 BP 1481 EP 1491 DI 10.1016/j.chembiol.2013.09.021 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 283TQ UT WOS:000329270300007 PM 24239007 ER PT J AU Licata, SC Shinday, NM Huizenga, MN Darnell, SB Sangrey, GR Rudolph, U Rowlett, JK Sadri-Vakili, G AF Licata, Stephanie C. Shinday, Nina M. Huizenga, Megan N. Darnell, Shayna B. Sangrey, Gavin R. Rudolph, Uwe Rowlett, James K. Sadri-Vakili, Ghazaleh TI Alterations in Brain-Derived Neurotrophic Factor in the Mouse Hippocampus Following Acute but Not Repeated Benzodiazepine Treatment SO PLOS ONE LA English DT Article ID LONG-TERM POTENTIATION; GAMMA-AMINOBUTYRIC-ACID; C-FOS EXPRESSION; PITUITARY-ADRENOCORTICAL AXIS; RAT BDNF-GENE; GABA(A) RECEPTORS; MESSENGER-RNA; IMMUNOCYTOCHEMICAL DISTRIBUTION; HISTONE ACETYLATION; HUNTINGTONS-DISEASE AB Benzodiazepines (BZs) are safe drugs for treating anxiety, sleep, and seizure disorders, but their use also results in unwanted effects including memory impairment, abuse, and dependence. The present study aimed to reveal the molecular mechanisms that may contribute to the effects of BZs in the hippocampus (HIP), an area involved in drug-related plasticity, by investigating the regulation of immediate early genes following BZ administration. Previous studies have demonstrated that both brain derived neurotrophic factor (BDNF) and c-Fos contribute to memory-and abuse-related processes that occur within the HIP, and their expression is altered in response to BZ exposure. In the current study, mice received acute or repeated administration of BZs and HIP tissue was analyzed for alterations in BDNF and c-Fos expression. Although no significant changes in BDNF or c-Fos were observed in response to twice-daily intraperitoneal (i.p.) injections of diazepam (10 mg/kg + 5 mg/kg) or zolpidem (ZP; 2.5 mg/kg + 2.5 mg/kg), acute i.p. administration of both triazolam (0.03 mg/kg) and ZP (1.0 mg/kg) decreased BDNF protein levels within the HIP relative to vehicle, without any effect on c-Fos. ZP specifically reduced exon IV-containing BDNF transcripts with a concomitant increase in the association of methyl-CpG binding protein 2 (MeCP2) with BDNF promoter IV, suggesting that MeCP2 activity at this promoter may represent a ZP-specific mechanism for reducing BDNF expression. ZP also increased the association of phosphorylated cAMP response element binding protein (pCREB) with BDNF promoter I. Future work should examine the interaction between ZP and DNA as the cause for altered gene expression in the HIP, given that BZs can enter the nucleus and intercalate into DNA directly. C1 [Licata, Stephanie C.; Rudolph, Uwe] McLean Hosp, Belmont, MA 02178 USA. [Shinday, Nina M.; Rowlett, James K.] New England Reg Primate Res Ctr, Southborough, MA 01772 USA. [Huizenga, Megan N.; Darnell, Shayna B.; Sangrey, Gavin R.; Sadri-Vakili, Ghazaleh] Massachusetts Gen Hosp, Charlestown, MA 02114 USA. [Licata, Stephanie C.; Shinday, Nina M.; Huizenga, Megan N.; Darnell, Shayna B.; Sangrey, Gavin R.; Rudolph, Uwe; Rowlett, James K.; Sadri-Vakili, Ghazaleh] Harvard Univ, Sch Med, Boston, MA USA. RP Sadri-Vakili, G (reprint author), Massachusetts Gen Hosp, Charlestown, MA 02114 USA. EM gsadrivakili@partners.org FU National Institutes of Health [DA011792, AG035361, RR000168/OD011103, DA015036, DA033795] FX This study was funded collectively by the National Institutes of Health (http://www.nih.gov/) grants DA011792, AG035361, RR000168/OD011103, DA015036, and DA033795. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 82 TC 11 Z9 13 U1 2 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 19 PY 2013 VL 8 IS 12 AR UNSP e84806 DI 10.1371/journal.pone.0084806 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 276HY UT WOS:000328741900069 PM 24367698 ER PT J AU Que, YA Hazan, R Strobel, B Maura, D He, JX Kesarwani, M Panopoulos, P Tsurumi, A Giddey, M Wilhelmy, J Mindrinos, MN Rahme, LG AF Que, Yok-Ai Hazan, Ronen Strobel, Benjamin Maura, Damien He, Jianxin Kesarwani, Meenu Panopoulos, Panagiotis Tsurumi, Amy Giddey, Marlyse Wilhelmy, Julie Mindrinos, Michael N. Rahme, Laurence G. TI A Quorum Sensing Small Volatile Molecule Promotes Antibiotic Tolerance in Bacteria SO PLOS ONE LA English DT Article ID CYSTIC-FIBROSIS LUNG; PSEUDOMONAS-AERUGINOSA; PERSISTER CELLS; ESCHERICHIA-COLI; MULTIDRUG TOLERANCE; MECHANISM; GENE; MVFR; 2-AMINOACETOPHENONE; IDENTIFICATION AB Bacteria can be refractory to antibiotics due to a sub-population of dormant cells, called persisters that are highly tolerant to antibiotic exposure. The low frequency and transience of the antibiotic tolerant "persister" trait has complicated elucidation of the mechanism that controls antibiotic tolerance. In this study, we show that 2' Aminoacetophenone (2-AA), a poorly studied but diagnostically important small, volatile molecule produced by the recalcitrant gram-negative human pathogen Pseudomonas aeruginosa, promotes antibiotic tolerance in response to quorum-sensing (QS) signaling. Our results show that 2-AA mediated persister cell accumulation occurs via alteration of the expression of genes involved in the translational capacity of the cell, including almost all ribosomal protein genes and other translation-related factors. That 2-AA promotes persisters formation also in other emerging multi-drug resistant pathogens, including the non 2-AA producer Acinetobacter baumannii implies that 2-AA may play an important role in the ability of gram-negative bacteria to tolerate antibiotic treatments in polymicrobial infections. Given that the synthesis, excretion and uptake of QS small molecules is a common hallmark of prokaryotes, together with the fact that the translational machinery is highly conserved, we posit that modulation of the translational capacity of the cell via QS molecules, may be a general, widely distributed mechanism that promotes antibiotic tolerance among prokaryotes. C1 [Que, Yok-Ai; Hazan, Ronen; Strobel, Benjamin; Maura, Damien; He, Jianxin; Kesarwani, Meenu; Panopoulos, Panagiotis; Tsurumi, Amy; Rahme, Laurence G.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Que, Yok-Ai; Hazan, Ronen; Strobel, Benjamin; Maura, Damien; He, Jianxin; Kesarwani, Meenu; Panopoulos, Panagiotis; Tsurumi, Amy; Rahme, Laurence G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Que, Yok-Ai; Hazan, Ronen; Strobel, Benjamin; Maura, Damien; He, Jianxin; Kesarwani, Meenu; Panopoulos, Panagiotis; Tsurumi, Amy; Rahme, Laurence G.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Que, Yok-Ai; Hazan, Ronen; Strobel, Benjamin; Maura, Damien; He, Jianxin; Kesarwani, Meenu; Panopoulos, Panagiotis; Tsurumi, Amy; Rahme, Laurence G.] Shriners Hosp Children, Boston, MA USA. [Wilhelmy, Julie; Mindrinos, Michael N.] Stanford Univ, Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA. [Hazan, Ronen] Hebrew Univ Jerusalem, Inst Dent Sci, Jerusalem, Israel. [Hazan, Ronen] Hebrew Univ Jerusalem, Sch Dent Med, Jerusalem, Israel. [Giddey, Marlyse] Univ Lausanne, Dept Fundamental Microbiol, Lausanne, Switzerland. RP Rahme, LG (reprint author), Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. EM rahme@molbio.mgh.harvard.edu FU NIH [AI105902, R56AI063433]; Swiss National Science Foundation/Swiss Medical Association (FMH) [PASMP3-123226]; SICPA Foundation; Shriners' Hospitals Research Fellowship [8494]; [8770] FX This work was supported by the Shriners' research grant #8770, and NIH grants AI105902 and R56AI063433 to LGR. YAQ was supported by a Swiss National Science Foundation/Swiss Medical Association (FMH) grant #PASMP3-123226 and a grant from the SICPA Foundation. RH was supported by Shriners' Hospitals Research Fellowship #8494. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 55 TC 20 Z9 21 U1 4 U2 24 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 19 PY 2013 VL 8 IS 12 AR UNSP e80140 DI 10.1371/journal.pone.0080140 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 276HY UT WOS:000328741900001 PM 24367477 ER PT J AU Kieffer-Kwon, KR Tang, ZH Mathe, E Qian, JS Sung, MH Li, GL Resch, W Baek, S Pruett, N Grontved, L Vian, L Nelson, S Zare, H Hakim, O Reyon, D Yamane, A Nakahashi, H Kovalchuk, AL Zou, JZ Joung, JK Sartorelli, V Wei, CL Ruan, XA Hager, GL Ruan, YJ Casellas, R AF Kieffer-Kwon, Kyong-Rim Tang, Zhonghui Mathe, Ewy Qian, Jason Sung, Myong-Hee Li, Guoliang Resch, Wolfgang Baek, Songjoon Pruett, Nathanael Grontved, Lars Vian, Laura Nelson, Steevenson Zare, Hossein Hakim, Ofir Reyon, Deepak Yamane, Arito Nakahashi, Hirotaka Kovalchuk, Alexander L. Zou, Jizhong Joung, J. Keith Sartorelli, Vittorio Wei, Chia-Lin Ruan, Xiaoan Hager, Gordon L. Ruan, Yijun Casellas, Rafael TI Interactome Maps of Mouse Gene Regulatory Domains Reveal Basic Principles of Transcriptional Regulation SO CELL LA English DT Article ID ACTIVATION-INDUCED DEAMINASE; EMBRYONIC STEM-CELLS; LONG NONCODING RNAS; HUMAN GENOME; CHROMATIN INTERACTIONS; AID EXPRESSION; ENHANCERS; LYMPHOCYTES; ELEMENTS; RECOMBINATION AB A key finding of the ENCODE project is that the enhancer landscape of mammalian cells undergoes marked alterations during ontogeny. However, the nature and extent of these changes are unclear. As part of the NIH Mouse Regulome Project, we here combined DNaseI hypersensitivity, ChIP-seq, and ChIA-PET technologies to map the promoter-enhancer interactomes of pluripotent ES cells and differentiated B lymphocytes. We confirm that enhancer usage varies widely across tissues. Unexpectedly, we find that this feature extends to broadly transcribed genes, including Myc and Pim1 cell-cycle regulators, which associate with an entirely different set of enhancers in ES and B cells. By means of high-resolution CpG methylomes, genome editing, and digital footprinting, we show that these enhancers recruit lineage-determining factors. Furthermore, we demonstrate that the turning on and off of enhancers during development correlates with promoter activity. We propose that organisms rely on a dynamic enhancer landscape to control basic cellular functions in a tissue-specific manner. C1 [Kieffer-Kwon, Kyong-Rim; Mathe, Ewy; Qian, Jason; Resch, Wolfgang; Pruett, Nathanael; Vian, Laura; Nelson, Steevenson; Yamane, Arito; Nakahashi, Hirotaka; Casellas, Rafael] NIAMS, NIH, Bethesda, MD 20892 USA. [Tang, Zhonghui; Li, Guoliang; Ruan, Xiaoan; Ruan, Yijun] Univ Connecticut, Jackson Lab Genom Med, Farmington, CT 06030 USA. [Tang, Zhonghui; Li, Guoliang; Ruan, Xiaoan; Ruan, Yijun] Univ Connecticut, Dept Genet & Dev Biol, Farmington, CT 06030 USA. [Sung, Myong-Hee; Baek, Songjoon; Grontved, Lars; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. [Zare, Hossein; Sartorelli, Vittorio] NIAMS, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA. [Hakim, Ofir] Bar Ilan Univ, IL-5290002 Ramat Gan, Israel. [Reyon, Deepak; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Mol Pathol Unit, Charlestown, MA 02129 USA. [Reyon, Deepak; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. [Reyon, Deepak; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Kovalchuk, Alexander L.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Zou, Jizhong] NIAMS, Lab Stem Cell Biol, NIH, Bethesda, MD 20892 USA. [Wei, Chia-Lin] DOE Joint Genome Inst, Walnut Creek, CA 94598 USA. [Casellas, Rafael] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Casellas, R (reprint author), NIAMS, NIH, Bethesda, MD 20892 USA. EM rafael.casellas@nih.gov RI Li, Guoliang/I-1494-2015; OI Li, Guoliang/0000-0003-1601-6640; Grontved, Lars/0000-0002-6735-8483 FU Intramural Research Program of NIAMS; NCI; internal Jackson Laboratory fund [JAX19020120]; NIH [DP1 GM105378, P50 HG005550]; Defense Advanced Research Projects Agency [W911NF-11-2-0056]; Jim and Ann Orr Massachusetts General Hospital Research Scholar Award; NIH UGSP program FX We thank Kefei Yu for CH12 cells and protocols; J. Simone and J. Lay for cell sorting; G. Gutierrez for technical assistance with Illumina analyzer. This work was supported by the Intramural Research Program of NIAMS and NCI, and internal Jackson Laboratory fund JAX19020120 to Y.R. J.K.J. was supported by NIH grants DP1 GM105378 and P50 HG005550, the Defense Advanced Research Projects Agency grant W911NF-11-2-0056 and The Jim and Ann Orr Massachusetts General Hospital Research Scholar Award. J. Q. was supported by the NIH UGSP program. All animal experiments were performed according to NIH guidelines. High-performance computation was performed using NIH Helix Systems (http://helix.nih.gov). J. K. J. has a financial interest in Transposagen Biopharmaceuticals. J.K.J.'s interests were reviewed and are managed by Massachusetts General Hospital and Partners HealthCare in accordance with their conflict of interest policies. NR 49 TC 116 Z9 120 U1 3 U2 44 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD DEC 19 PY 2013 VL 155 IS 7 BP 1507 EP 1520 DI 10.1016/j.cell.2013.11.039 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 275QW UT WOS:000328693300008 PM 24360274 ER PT J AU Gomes, AP Price, NL Ling, AJY Moslehi, JJ Montgomery, MK Rajman, L White, JP Teodor, JS Wrann, CD Hubbard, BP Mercken, EM Palmeira, CM de Cabo, R Rolo, AP Turner, N Bell, EL Sinclair, DA AF Gomes, Ana P. Price, Nathan L. Ling, Alvin J. Y. Moslehi, Javid J. Montgomery, Magdalene K. Rajman, Luis White, James P. Teodor, Joao S. Wrann, Christiane D. Hubbard, Basil P. Mercken, Evi M. Palmeira, Carlos M. de Cabo, Rafael Rolo, Anabela P. Turner, Nigel Bell, Eric L. Sinclair, David A. TI Declining NAD(+) Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging SO CELL LA English DT Article ID INDUCIBLE FACTOR 1-ALPHA; CANCER-CELL METABOLISM; FATTY-ACID OXIDATION; GLUCOSE-HOMEOSTASIS; LIFE-SPAN; C-MYC; NICOTINAMIDE MONONUCLEOTIDE; CALORIE RESTRICTION; ENERGY-EXPENDITURE; SIRT1 DEACETYLASE AB Ever since eukaryotes subsumed the bacterial ancestor of mitochondria, the nuclear and mitochondrial genomes have had to closely coordinate their activities, as each encode different subunits of the oxidative phosphorylation (OXPHOS) system. Mitochondrial dysfunction is a hallmark of aging, but its causes are debated. We show that, during aging, there is a specific loss of mitochondrial, but not nuclear, encoded OXPHOS subunits. We trace the cause to an alternate PGC-1 alpha/beta-independent pathway of nuclear-mitochondrial communication that is induced by a decline in nuclear NAD(+) and the accumulation of HIF-1 alpha under normoxic conditions, with parallels to Warburg reprogramming. Deleting SIRT1 accelerates this process, whereas raising NAD(+) levels in old mice restores mitochondrial function to that of a young mouse in a SIRT1-dependent manner. Thus, a pseudohypoxic state that disrupts PGC-1 alpha/beta-independent nuclear-mitochondrial communication contributes to the decline in mitochondrial function with age, a process that is apparently reversible. C1 [Gomes, Ana P.; Price, Nathan L.; Ling, Alvin J. Y.; Rajman, Luis; Hubbard, Basil P.; Sinclair, David A.] Harvard Univ, Sch Med, Dept Genet, Glenn Labs Biol Mech Aging, Boston, MA 02115 USA. [Gomes, Ana P.; Teodor, Joao S.; Palmeira, Carlos M.; Rolo, Anabela P.] Ctr Neurosci & Cell Biol, P-3004517 Coimbra, Portugal. [Gomes, Ana P.; Teodor, Joao S.; Palmeira, Carlos M.] Univ Coimbra, Fac Sci & Technol, Dept Life Sci, P-3004517 Coimbra, Portugal. [Moslehi, Javid J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med Oncol, Boston, MA 02115 USA. [Moslehi, Javid J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Moslehi, Javid J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med,Dept Med, Boston, MA 02115 USA. [Montgomery, Magdalene K.; Turner, Nigel; Sinclair, David A.] Univ New S Wales, Sch Med Sci, Dept Pharmacol, Sydney, NSW 2052, Australia. [White, James P.; Wrann, Christiane D.] Harvard Univ, Sch Med, Dept Cell Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Mercken, Evi M.; de Cabo, Rafael] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. [Rolo, Anabela P.] Univ Aveiro, Dept Biol, P-3810193 Aveiro, Portugal. [Bell, Eric L.] MIT, Dept Biol, Paul F Glenn Lab Sci Aging, Cambridge, MA 02139 USA. RP Sinclair, DA (reprint author), Harvard Univ, Sch Med, Dept Genet, Glenn Labs Biol Mech Aging, Boston, MA 02115 USA. EM david_sinclair@hms.harvard.edu RI Teodoro, Joao/F-5432-2011; de Cabo, Rafael/J-5230-2016; Turner, Nigel/H-7176-2013; OI Teodoro, Joao/0000-0002-1244-275X; de Cabo, Rafael/0000-0002-3354-2442; Turner, Nigel/0000-0002-0119-9328; Sinclair, David/0000-0002-9936-436X; , rafael/0000-0003-2830-5693 FU NIH/NIA; Glenn Foundation for Medical Research; United Mitochondrial Disease Foundation; Juvenile Diabetes Research Foundation; Portuguese Foundation for Science and Technology [SFRH/BD/44674/2008]; NSERC PGS-D fellowship; Australian Research Council Future Fellowship FX The Sinclair lab is supported by the NIH/NIA, the Glenn Foundation for Medical Research, the United Mitochondrial Disease Foundation, the Juvenile Diabetes Research Foundation, and a gift from the Schulak family. A. P. G. was supported by the Portuguese Foundation for Science and Technology (SFRH/BD/44674/2008) and B. P. H. by an NSERC PGS-D fellowship. N.T. is supported by an Australian Research Council Future Fellowship. We are grateful to Michael Bonkowski, Carlos Daniel de Magalhaes Filho, Meghan Rego, Nikolina Dioufa, and David Zhang for technical advice and experimental assistance; William Kaelin Jr. for kindly providing the EglN1 KO mice; Daniel Kelly, John Rumsay, and Teresa Leone for unpublished PGC-1 alpha/beta KO myoblasts and advice; Bruce Spiegelman for PGC-1 alpha null myoblasts and advice; and Pere Puigserver and Zachary Gerhart-Hines for a SIRT1 adenovirus. D. A. S. is a consultant to Cohbar, OvaScience, HorizonScience, Segterra, MetroBiotech, and GlaxoSmithKline. Cohbar, MetroBiotech, and GlaxoSmithKline work on mitochondrially derived peptides, NAD+, and sirtuin modulation, respectively. NR 55 TC 253 Z9 258 U1 11 U2 96 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD DEC 19 PY 2013 VL 155 IS 7 BP 1624 EP 1638 DI 10.1016/j.cell.2013.11.037 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 275QW UT WOS:000328693300017 PM 24360282 ER PT J AU Wong, CA Davis, JC Asch, DA Shugerman, RP AF Wong, Charlene A. Davis, Jeremiah C. Asch, David A. Shugerman, Richard P. TI Political Tug-of-War and Pediatric Residency Funding SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID GRADUATE MEDICAL-EDUCATION AB The recent government shutdown led to effective defunding of the Children's Hospitals Graduate Medical Education (CHGME) Payment Program. The funding lapse highlights the danger of subjecting GME funding to a politicized process. On October 1, 2013, without a continuing resolution in place to support its budget, the U.S. federal government partially closed. One of many effects of the government shutdown was the defunding of the Children's Hospitals Graduate Medical Education (CHGME) Payment Program. Fifty-five freestanding children's hospitals currently receive CHGME funds. These hospitals train almost 30% of the general pediatricians, 44% of the pediatric medical and surgical subspecialists, and the majority of the pediatric physician-researchers in the United States.(1),(2) Capable of providing highly specialized care for pediatric patients with complex and acute conditions, freestanding children's hospitals are at the apex of ... C1 [Wong, Charlene A.; Asch, David A.] Univ Penn, Robert Wood Johnson Fdn, Clin Scholars Program, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Davis, Jeremiah C.; Shugerman, Richard P.] Seattle Childrens Hosp, Pediat Residency Program, Seattle, WA USA. [Davis, Jeremiah C.; Shugerman, Richard P.] Univ Washington, Sch Med, Seattle, WA USA. RP Wong, CA (reprint author), Univ Penn, Robert Wood Johnson Fdn, Clin Scholars Program, Philadelphia, PA 19104 USA. OI Asch, David/0000-0002-7970-286X NR 5 TC 1 Z9 1 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 19 PY 2013 VL 369 IS 25 BP 2372 EP 2374 DI 10.1056/NEJMp1312898 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 274DQ UT WOS:000328586000004 PM 24171507 ER PT J AU Yu, CC Fornoni, A Weins, A Hakroush, S Maiguel, D Sageshima, J Chen, L Ciancio, G Faridi, MH Behr, D Campbell, KN Chang, JM Chen, HC Oh, J Faul, C Arnaout, MA Fiorina, P Gupta, V Greka, A Burke, GW Mundel, P AF Yu, Chih-Chuan Fornoni, Alessia Weins, Astrid Hakroush, Samy Maiguel, Dony Sageshima, Junichiro Chen, Linda Ciancio, Gaetano Faridi, Mohd Hafeez Behr, Daniel Campbell, Kirk N. Chang, Jer-Ming Chen, Hung-Chun Oh, Jun Faul, Christian Arnaout, M. Amin Fiorina, Paolo Gupta, Vineet Greka, Anna Burke, George W., III Mundel, Peter TI Abatacept in B7-1-Positive Proteinuric Kidney Disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RHEUMATOID-ARTHRITIS; INTEGRIN ACTIVATION; PODOCYTES; TALIN AB Abatacept (cytotoxic T-lymphocyte-associated antigen 4-immunoglobulin fusion protein [CTLA-4-Ig]) is a costimulatory inhibitor that targets B7-1 (CD80). The present report describes five patients who had focal segmental glomerulosclerosis (FSGS) (four with recurrent FSGS after transplantation and one with primary FSGS) and proteinuria with B7-1 immunostaining of podocytes in kidney-biopsy specimens. Abatacept induced partial or complete remissions of proteinuria in these patients, suggesting that B7-1 may be a useful biomarker for the treatment of some glomerulopathies. Our data indicate that abatacept may stabilize 1-integrin activation in podocytes and reduce proteinuria in patients with B7-1-positive glomerular disease. C1 [Yu, Chih-Chuan; Weins, Astrid; Hakroush, Samy; Maiguel, Dony; Arnaout, M. Amin; Greka, Anna; Mundel, Peter] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Yu, Chih-Chuan; Weins, Astrid; Hakroush, Samy; Behr, Daniel; Arnaout, M. Amin; Greka, Anna; Mundel, Peter] Harvard Univ, Sch Med, Boston, MA USA. [Weins, Astrid] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Fiorina, Paolo] Childrens Hosp, Div Nephrol, Boston, MA 02115 USA. [Yu, Chih-Chuan] Kaohsiung Med Univ, Coll Med, Grad Inst Med, Kaohsiung, Taiwan. [Chang, Jer-Ming; Chen, Hung-Chun] Kaohsiung Med Univ, Coll Med, Dept Internal Med, Kaohsiung, Taiwan. [Fornoni, Alessia; Maiguel, Dony; Faridi, Mohd Hafeez; Faul, Christian; Gupta, Vineet] Univ Miami, Miller Sch Med, Div Nephrol & Hypertens, Miami, FL 33136 USA. [Sageshima, Junichiro; Chen, Linda; Ciancio, Gaetano; Burke, George W., III] Univ Miami, Miller Sch Med, Lilian Jean Kaplan Div Kidney Pancreas Transplant, Miami Transplant Inst,Dept Surg, Miami, FL 33136 USA. [Campbell, Kirk N.] Mt Sinai Sch Med, Div Nephrol, New York, NY USA. [Oh, Jun] Univ Med Ctr Hamburg Eppendorf, Childrens Hosp, Hamburg, Germany. RP Mundel, P (reprint author), Massachusetts Gen Hosp, Div Nephrol, 149 13th St, Charlestown, MA 02129 USA. EM mundel.peter@mgh.harvard.edu FU National Institutes of Health [DK57683, DK062472, DK093783, DK068253, HL109582, DK0903616, DK090316, DK083511, DK093746]; Boston Area Diabetes Endocrinology Research Center; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK057521]; Deutsche Forschungsgemeinschaft [HA 6334/1-1]; NephCure Foundation; Transplant Foundation of South Florida; American Society of Nephrology; NephCure Young Investigator Award FX Supported by grants from the National Institutes of Health (DK57683 and DK062472, to Dr. Mundel; DK093783, to Dr. Weins; DK068253 and HL109582, to Dr. Gupta; DK0903616, to Drs. Fornoni and Burke; and DK090316, DK083511, and DK093746, to Dr. Greka), the Boston Area Diabetes Endocrinology Research Center and the National Institute of Diabetes and Digestive and Kidney Diseases (P30DK057521, to Dr. Greka), Deutsche Forschungsgemeinschaft (HA 6334/1-1, to Dr. Hakroush), and the NephCure Foundation and Transplant Foundation of South Florida (to Drs. Fornoni and Burke), and by an American Society of Nephrology Gottschalk Career Development Award and a NephCure Young Investigator Award (to Dr. Greka). NR 15 TC 112 Z9 121 U1 1 U2 11 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 19 PY 2013 VL 369 IS 25 BP 2416 EP 2423 DI 10.1056/NEJMoa1304572 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 274DQ UT WOS:000328586000009 PM 24206430 ER PT J AU Roh, EK Vleugels, RA Hoang, MP AF Roh, Ellen K. Vleugels, Ruth Ann Hoang, Mai P. TI Case 39-2013: A 57-Year-Old Woman with Painful Bullous Skin Lesions SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PEMPHIGUS ERYTHEMATOSUS; CLINICAL-FEATURES; DIAGNOSIS; FOLIACEUS; VULGARIS AB A 57-year-old woman was admitted to the hospital because of a 19-month history of recurrent painful bullous and erosive skin lesions. Multiple skin-biopsy specimens had yielded diverse diagnoses. A diagnostic procedure was performed. Presentation of CaseDr. Amir Aboutalebi (Dermatology): A 57-year-old woman was admitted to this hospital because of recurrent painful bullous and erosive skin lesions. Approximately 19 months before admission, 1 week after the patient had begun taking citalopram, the development of oral erosions, tongue swelling, and urticarial lesions, approximately 1 cm in diameter, on her torso occurred. These symptoms were followed during the next several weeks by joint pain and swelling in her hands, fatigue, and low-grade fevers. Citalopram was stopped, and antihistamines were prescribed, which the patient reported that she did not take for religious reasons; during the next ... C1 [Roh, Ellen K.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Hoang, Mai P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Vleugels, Ruth Ann] Harvard Univ, Brigham & Womens Hosp, Dept Dermatol, Sch Med, Boston, MA 02115 USA. [Roh, Ellen K.; Vleugels, Ruth Ann] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hoang, Mai P.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Roh, EK (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. FU WorldCare Clinical FX Dr. Roh reports receiving consulting fees from WorldCare Clinical. No other potential conflict of interest relevant to this article was reported. NR 18 TC 3 Z9 3 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 19 PY 2013 VL 369 IS 25 BP 2438 EP 2449 DI 10.1056/NEJMcpc1215967 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 274DQ UT WOS:000328586000012 PM 24350953 ER PT J AU Finkelstein, JS Yu, EW Burnett-Bowie, SAM AF Finkelstein, Joel S. Yu, Elaine W. Burnett-Bowie, Sherri-Ann M. TI Gonadal Steroids and Body Composition, Strength, and Sexual Function in Men SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID TYPE-1 DIABETES-MELLITUS; SERUM CYSTATIN-C; RISK; HYPERGLYCEMIA; DISEASE AB To the Editor: The meta-analysis by Shlipak et al. (Sept. 5 issue)(1) shows that a cystatin C-based estimated glomerular filtration rate (eGFR) offers improvements in predicting risks of death and end-stage renal disease across diverse populations. In their editorial, Ingelfinger and Marsden(2) caution that results cannot be applied to Asian and Hispanic patients except by extrapolation. Also, diabetes was underrepresented in the sample of patients with chronic kidney disease; it was present in only 9% of participants. Further, more information is still needed about the use of cystatin C in pregnant women, patients who have undergone renal transplantation, and children. ... C1 [Finkelstein, Joel S.; Yu, Elaine W.; Burnett-Bowie, Sherri-Ann M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Finkelstein, JS (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jfinkelstein@partners.org NR 13 TC 21 Z9 21 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 19 PY 2013 VL 369 IS 25 BP 2457 EP 2457 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 274DQ UT WOS:000328586000019 PM 24350954 ER PT J AU Shlipak, MG Coresh, J Gansevoort, RT AF Shlipak, Michael G. Coresh, Josef Gansevoort, Ron T. TI Cystatin C versus Creatinine for Kidney Function-Based Risk SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Shlipak, Michael G.] San Francisco VA Med Ctr, San Francisco, CA USA. [Coresh, Josef] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Gansevoort, Ron T.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. RP Shlipak, MG (reprint author), San Francisco VA Med Ctr, San Francisco, CA USA. EM ckdpc@jhmi.edu NR 0 TC 9 Z9 9 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 19 PY 2013 VL 369 IS 25 BP 2459 EP 2459 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 274DQ UT WOS:000328586000023 PM 24350959 ER PT J AU Haibe-Kains, B El-Hachem, N Birkbak, NJ Jin, AC Beck, AH Aerts, HJWL Quackenbush, J AF Haibe-Kains, Benjamin El-Hachem, Nehme Birkbak, Nicolai Juul Jin, Andrew C. Beck, Andrew H. Aerts, Hugo J. W. L. Quackenbush, John TI Inconsistency in large pharmacogenomic studies SO NATURE LA English DT Article ID ANTICANCER DRUG-SENSITIVITY; EXPRESSION PROFILES; CANCER; GENE; RESPONSES; SET AB Two large-scale pharmacogenomic studies were published recently in this journal. Genomic data are well correlated between studies; however, the measured drug response data are highly discordant. Although the source of inconsistencies remains uncertain, it has potential implications for using these outcome measures to assess gene-drug associations or select potential anticancer drugs on the basis of their reported results. C1 [Haibe-Kains, Benjamin; El-Hachem, Nehme] Univ Montreal, Inst Rech Clin Montreal, Montreal, PQ, Canada. [Haibe-Kains, Benjamin] Univ Hlth Network, Princess Margaret Canc Ctr, Ontario Canc Inst, Toronto, ON M5G 2M9, Canada. [Birkbak, Nicolai Juul] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Jin, Andrew C.; Beck, Andrew H.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Jin, Andrew C.; Beck, Andrew H.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Aerts, Hugo J. W. L.; Quackenbush, John] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Aerts, Hugo J. W. L.; Quackenbush, John] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02215 USA. [Aerts, Hugo J. W. L.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol & Radiol,Med Sch, Boston, MA 02215 USA. [Aerts, Hugo J. W. L.] Maastricht Univ, Dept Radiat Oncol, NL-6200 MD Maastricht, Netherlands. [Quackenbush, John] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. RP Haibe-Kains, B (reprint author), Univ Montreal, Inst Rech Clin Montreal, Montreal, PQ, Canada. EM bhaibeka@uhnresearch.ca RI Haibe-Kains, Benjamin/D-3702-2011; Aerts, Hugo/P-6350-2015 OI Haibe-Kains, Benjamin/0000-0002-7684-0079; Aerts, Hugo/0000-0002-2122-2003 FU IRCM; Klarman Family Foundation; NIH [CA087969]; Villum Kann Rasmussen Foundation; Dr Miriam and Sheldon G. Adelson Medical Research Foundation; NCI GAME-ON Cancer Post-GWAS initiative [U19 CA148065-01] FX We thank J. Archambault for his insightful comments on the comparative study between experimental protocols used in the large pharmacogenomic studies investigated in this work. The authors would like to thank the investigators of the Cancer Genome Project, the Cancer Cell Line Encyclopedia and the GlaxoSmithKline cell line study who have made their invaluable data available to the scientific community. N.E.-H. was supported by an IRCM doctoral fellowship. A. H. B. was supported by an award from the Klarman Family Foundation and by support from NIH grant CA087969. N.J.B. was funded The Villum Kann Rasmussen Foundation. J. Q. was supported grants from the Dr Miriam and Sheldon G. Adelson Medical Research Foundation and from the NCI GAME-ON Cancer Post-GWAS initiative (U19 CA148065-01). NR 18 TC 125 Z9 126 U1 4 U2 34 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 19 PY 2013 VL 504 IS 7480 BP 389 EP + DI 10.1038/nature12831 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 273ZR UT WOS:000328575300042 PM 24284626 ER PT J AU Erdmann, J Stark, K Esslinger, UB Rumpf, PM Koesling, D de Wit, C Kaiser, FJ Braunholz, D Medack, A Fischer, M Zimmermann, ME Tennstedt, S Graf, E Eck, S Aherrahrou, Z Nahrstaedt, J Willenborg, C Bruse, P Braenne, I Nothen, MM Hofmann, P Braund, PS Mergia, E Reinhard, W Burgdorf, C Schreiber, S Balmforth, AJ Hall, AS Bertram, L Steinhagen-Thiessen, E Li, SC Marz, W Reilly, M Kathiresan, S McPherson, R Walter, U Ott, J Samani, NJ Strom, TM Meitinger, T Hengstenberg, C Schunkert, H AF Erdmann, Jeanette Stark, Klaus Esslinger, Ulrike B. Rumpf, Philipp Moritz Koesling, Doris de Wit, Cor Kaiser, Frank J. Braunholz, Diana Medack, Anja Fischer, Marcus Zimmermann, Martina E. Tennstedt, Stephanie Graf, Elisabeth Eck, Sebastian Aherrahrou, Zouhair Nahrstaedt, Janja Willenborg, Christina Bruse, Petra Braenne, Ingrid Noethen, Markus M. Hofmann, Per Braund, Peter S. Mergia, Evanthia Reinhard, Wibke Burgdorf, Christof Schreiber, Stefan Balmforth, Anthony J. Hall, Alistair S. Bertram, Lars Steinhagen-Thiessen, Elisabeth Li, Shu-Chen Maerz, Winfried Reilly, Muredach Kathiresan, Sekar McPherson, Ruth Walter, Ulrich Ott, Jurg Samani, Nilesh J. Strom, Tim M. Meitinger, Thomas Hengstenberg, Christian Schunkert, Heribert CA CARDIoGRAM TI Dysfunctional nitric oxide signalling increases risk of myocardial infarction SO NATURE LA English DT Article ID CORONARY-ARTERY-DISEASE; SOLUBLE GUANYLATE-CYCLASE; GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; ADULTS AB Myocardial infarction, a leading cause of death intheWesternworld(1), usually occurs when the fibrous cap overlying an atherosclerotic plaque in a coronary artery ruptures. The resulting exposure of blood to the atherosclerotic material then triggers thrombus formation, which occludes the artery(2). The importance of genetic predisposition to coronary artery disease and myocardial infarction is best documented by the predictive value of a positive family history(3). Nextgeneration sequencing in families with several affected individuals has revolutionized mutation identification(4). Here we report the segregation of two private, heterozygous mutations in two functionally relatedgenes, GUCY1A3 (p.Leu163Phefs*24) andCCT7 (p.Ser525Leu), in an extended myocardial infarction family. GUCY1A3 encodes the alpha 1 subunit of soluble guanylyl cyclase (alpha 1-sGC)(5), and CCT7 encodes CCT eta, a member of the tailless complex polypeptide 1 ring complex(6), which, among other functions, stabilizes soluble guanylyl cyclase. After stimulation with nitric oxide, soluble guanylyl cyclase generates cGMP, which induces vasodilation and inhibits platelet activation(7). Wedemonstratein vitro that mutations inbothGUCY1A3 and CCT7 severely reduce alpha 1-sGC as well as beta 1-sGC protein content, and impair soluble guanylyl cyclase activity. Moreover, platelets from digenic mutation carriers contained less soluble guanylyl cyclase protein and consequently displayed reduced nitric-oxideinduced cGMP formation. Mice deficient in alpha 1-sGC protein displayed accelerated thrombus formation in themicrocirculation after local trauma. Starting with a severely affected family, we have identified a link between impaired soluble-guanylyl-cyclase-dependent nitric oxide signalling and myocardial infarction risk, possibly through accelerated thrombus formation. Reversing this defect may provide a new therapeutic target for reducing the risk of myocardial infarction. C1 [Erdmann, Jeanette; Medack, Anja; Tennstedt, Stephanie; Aherrahrou, Zouhair; Nahrstaedt, Janja; Willenborg, Christina; Bruse, Petra; Braenne, Ingrid] Med Univ Lubeck, Inst Integrat & Expt Genom, D-23562 Lubeck, Germany. [Erdmann, Jeanette; de Wit, Cor; Kaiser, Frank J.; Aherrahrou, Zouhair; Willenborg, Christina] German Ctr Cardiovasc Res DZHK, D-23562 Lubeck, Germany. [Stark, Klaus; Esslinger, Ulrike B.; Fischer, Marcus; Zimmermann, Martina E.] Univ Klinikum Regensburg, Klin & Poliklin Innere Med 2, D-93053 Regensburg, Germany. [Stark, Klaus] Univ Regensburg, Dept Genet Epidemiol, D-93053 Regensburg, Germany. [Esslinger, Ulrike B.] INSERM, UMR S937, Paris, France. [Rumpf, Philipp Moritz; Reinhard, Wibke; Burgdorf, Christof; Meitinger, Thomas; Hengstenberg, Christian; Schunkert, Heribert] Deutsch Herzzentrum Munich, D-80636 Munich, Germany. [Rumpf, Philipp Moritz; Reinhard, Wibke; Burgdorf, Christof; Meitinger, Thomas; Hengstenberg, Christian; Schunkert, Heribert] Tech Univ Munich, Klinikum Rechts Isar, Med Klin 1, D-80636 Munich, Germany. [Rumpf, Philipp Moritz; Reinhard, Wibke; Hengstenberg, Christian; Schunkert, Heribert] German Ctr Cardiovasc Res DZHK, D-80636 Munich, Germany. [Koesling, Doris; Mergia, Evanthia] Ruhr Univ Bochum, Dept Pharmacol & Toxicol, D-44801 Bochum, Germany. [de Wit, Cor] Med Univ Lubeck, Inst Physiol, D-23562 Lubeck, Germany. [Kaiser, Frank J.; Braunholz, Diana] Med Univ Lubeck, Inst Humangenet, D-23562 Lubeck, Germany. [Graf, Elisabeth; Eck, Sebastian; Strom, Tim M.; Meitinger, Thomas] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, D-85764 Neuherberg, Germany. [Graf, Elisabeth; Eck, Sebastian; Strom, Tim M.; Meitinger, Thomas] Tech Univ Munich, Inst Human Genet, D-81675 Munich, Germany. [Noethen, Markus M.; Hofmann, Per] Univ Bonn, Inst Human Genet, D-53127 Bonn, Germany. [Noethen, Markus M.] Univ Bonn, Res Ctr Life & Brain, Dept Genom, D-53127 Bonn, Germany. [Hofmann, Per] Univ Basel Hosp, Div Med Genet, CH-4003 Basel, Switzerland. [Hofmann, Per] Univ Basel, Dept Biomed, CH-4003 Basel, Switzerland. [Braund, Peter S.; Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester LE1 7RH, Leics, England. [Braund, Peter S.; Samani, Nilesh J.] Glenfield Gen Hosp, Leicester Natl Inst Hlth Res Biomed Res Unit Card, Leicester LE1 7RH, Leics, England. [Schreiber, Stefan] Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany. [Balmforth, Anthony J.] Univ Leeds, Leeds Inst Genet Hlth & Therapeut, Multidisciplinary Cardiovasc Res Ctr, Div Cardiovasc & Diabet Res, Leeds LS2 9JT, W Yorkshire, England. [Hall, Alistair S.] Univ Leeds, Leeds Inst Genet Hlth & Therapeut, Multidisciplinary Cardiovasc Res Ctr, Div Cardiovasc & Neuronal Remodelling, Leeds LS2 9JT, W Yorkshire, England. [Bertram, Lars] Max Planck Inst Mol Genet, Dept Vertebrate Genom, D-14195 Berlin, Germany. [Steinhagen-Thiessen, Elisabeth] Charite, Charite Res Grp Geriatr, D-10117 Berlin, Germany. [Li, Shu-Chen] Max Planck Inst Human Dev, Ctr Lifespan Psychol, D-14195 Berlin, Germany. [Li, Shu-Chen] Tech Univ Dresden, Dept Psychol, D-01062 Dresden, Germany. [Maerz, Winfried] Synlab Serv GmbH, Synlab Acad, D-68165 Mannheim, Germany. [Maerz, Winfried] Synlab Serv GmbH, Business Dev, D-68165 Mannheim, Germany. [Maerz, Winfried] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, A-8036 Graz, Austria. [Maerz, Winfried] Heidelberg Univ, Med Fac Mannheim, Med Clin 5, D-68167 Mannheim, Germany. [Reilly, Muredach] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02215 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02215 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02215 USA. [Kathiresan, Sekar] Broad Inst Harvard & Massachusetts Inst Technol M, Program Med & Populat Genet, Cambridge, MA 02215 USA. [McPherson, Ruth] Univ Ottawa, Inst Heart, Ottawa, ON K1Y 4W7, Canada. [Walter, Ulrich] Univ Med Mainz, CTH, D-55131 Mainz, Germany. [Walter, Ulrich] German Ctr Cardiovasc Res DZHK, D-55131 Mainz, Germany. [Ott, Jurg] Chinese Acad Sci, Inst Psychol, Beijing 100864, Peoples R China. [Ott, Jurg] Rockefeller Univ, Lab Stat Genet, New York, NY 10065 USA. RP Hengstenberg, C (reprint author), Deutsch Herzzentrum Munich, D-80636 Munich, Germany. EM jeanette.erdmann@iieg.uni-luebeck.de; hengstenberg@dhm.mhn.de RI de Wit, Cor/A-5560-2009; Schreiber, Stefan/B-6748-2008; Altshuler, David/A-4476-2009; Willenborg, Christina/D-2668-2012; Boehm, Bernhard/F-8750-2015; Gudnason, Vilmundur/K-6885-2015; Meitinger, Thomas/O-1318-2015; Bertram, Lars/K-3889-2015; Li, Shu-Chen/K-7838-2012; Erdmann, Jeanette/P-7513-2014 OI Assimes, Themistocles/0000-0003-2349-0009; Kleber, Marcus/0000-0003-0663-7275; Nothen, Markus/0000-0002-8770-2464; de Wit, Cor/0000-0003-4621-0399; Schreiber, Stefan/0000-0003-2254-7771; Altshuler, David/0000-0002-7250-4107; Willenborg, Christina/0000-0001-5217-6882; Gudnason, Vilmundur/0000-0001-5696-0084; Bertram, Lars/0000-0002-0108-124X; Li, Shu-Chen/0000-0002-5520-5789; Erdmann, Jeanette/0000-0002-4486-6231 FU Deutsche Forschungsgemeinschaft; German Federal Ministry of Education and Research (BMBF) [01GS0417, 01GS0832]; EU [LSHM-CT-2006-037593]; ENGAGE [201413]; GEUVADIS [261123]; binational BMBF/ANR funded project CARDomics [01KU0908A]; Universitat zu Lubeck; University Hospital of Regensburg, Germany; The German Federal Ministry for Education and Research [16SV5538]; NSFC from Chinese Government [30730057]; British Heart Foundation; Leicester NIHR Biomedical Research Unit in Cardiovascular Disease; BMBF [01EO1003]; DFG FX We thank all the family members who participated in this research. Without the continuous support of these patients over more than 15 years, the present work would not have been possible. We would like to thank S. Wrobel, S. Stark, A. Liebers, K. Franke, J. Stegmann-Frehse, M. Behrensen, M. Schmid, J. Eckhold, D. Wollner, U. Krabbe and J. Simon for technical assistance. Furthermore, we would like to thank M. Becker, N. Buchholz, I. Demuth, R. Eckardt, H. Heekeren, U. Lindenberger, M. Lovden, L. Muller, W. Nietfeld, G. Pawelec, F. Schmiedeck, T. Siedler and G. G. Wagner for their contributions to BASE-II. We also would like to thank S. Herterich and S. Gambaryan for advice, and B. Mayer, U. Hubauer, K.-H. Ameln and A. Grosshennig for help with GerMIFS. We thank WTCCC+ and the WTCCC-CAD2 investigators for access to their data. The study is supported by the Deutsche Forschungsgemeinschaft and the German Federal Ministry of Education and Research (BMBF) in the context of the German National Genome Research Network (NGFN-2 (01GS0417) and NGFN-plus (01GS0832)), the FP6 and FP7 EU-funded integrated projects Cardiogenics (LSHM-CT-2006-037593), ENGAGE (201413), and GEUVADIS (261123), the binational BMBF/ANR funded project CARDomics (01KU0908A), the local focus programs 'Kardiovaskulare Genomforschung' and 'Medizinische Genetik' of the Universitat zu Lubeck, and the University Hospital of Regensburg, Germany. The German Federal Ministry for Education and Research provided funding for BASE-II (BMBF; grant no. 16SV5538). Support by NSFC grant 30730057 from the Chinese Government (to J.O.) is gratefully acknowledged. N. J. S. holds a Chair funded by the British Heart Foundation, and is supported by the Leicester NIHR Biomedical Research Unit in Cardiovascular Disease. U. W. is supported by the BMBF(01EO1003). M. M. N. is a member of the DFG-funded Excellence Cluster ImmunoSensation. NR 28 TC 71 Z9 71 U1 3 U2 55 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD DEC 19 PY 2013 VL 504 IS 7480 BP 432 EP + DI 10.1038/nature12722 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 273ZR UT WOS:000328575300051 PM 24213632 ER PT J AU Yamaguchi, S Shen, L Liu, YT Sendler, D Zhang, Y AF Yamaguchi, Shinpei Shen, Li Liu, Yuting Sendler, Damian Zhang, Yi TI Role of Tet1 in erasure of genomic imprinting SO NATURE LA English DT Article ID PRIMORDIAL GERM-CELLS; DNA METHYLATION; POSTNATAL-DEVELOPMENT; GENE; 5-HYDROXYMETHYLCYTOSINE; DEMETHYLATION; DYNAMICS; 5-METHYLCYTOSINE; DEFICIENCY; EXPRESSION AB Genomic imprinting is an allele-specific gene expression system that is important for mammalian development and function(1). The molecular basis of genomic imprinting is allele-specific DNA methylation(1,2). Although it is well known that the de novo DNA methyltransferases Dnmt3a and Dnmt3b are responsible for the establishment of genomic imprinting(3), how the methylation mark is erased during primordial germ cell (PGC) reprogramming remains unclear. Tet1 is one of the ten-eleven translocation family proteins, which have the capacity to oxidize 5-methylcytosine (5mC)(4-6), specifically expressed in reprogramming PGCs(7). Here we report that Tet1 has a critical role in the erasure of genomic imprinting. We show that despite their identical genotype, progenies derived from mating between Tet1 knockout males and wild-type females exhibit a number of variable phenotypes including placental, fetal and postnatal growth defects, and early embryonic lethality. These defects are, at least in part, caused by the dysregulation of imprinted genes, such as Peg10 and Peg3, which exhibit aberrant hypermethylation in the paternal allele of differential methylated regions (DMRs). RNA-seq reveals extensive dysregulation of imprinted genes in the next generation due to paternal loss of Tet1 function. Genome-wide DNA methylation analysis of embryonic day 13.5 PGCs and sperm of Tet1 knockout mice revealed hypermethylation of DMRs of imprinted genes in sperm, which can be traced back to PGCs. Analysis of the DNA methylation dynamics in reprogramming PGCs indicates that Tet1 functions to wipe out remaining methylation, including imprinted genes, at the late reprogramming stage. Furthermore, we provide evidence supporting the role of Tet1 in the erasure of paternal imprints in the female germ line. Thus, our study establishes a critical function of Tet1 in the erasure of genomic imprinting. C1 [Yamaguchi, Shinpei; Shen, Li; Liu, Yuting; Sendler, Damian; Zhang, Yi] Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Yamaguchi, Shinpei; Liu, Yuting; Zhang, Yi] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Yamaguchi, Shinpei; Liu, Yuting; Zhang, Yi] Boston Childrens Hosp, Dept Pediat, Div Hematol Oncol, Boston, MA 02115 USA. [Zhang, Yi] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Zhang, Yi] Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Zhang, Y (reprint author), Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. EM yzhang@genetics.med.harvard.edu OI Yamaguchi, Shinpei/0000-0002-9377-4835 FU NIH [U01DK089565]; Japan Society for the Promotion of Science (JSPS) FX We thank W. Jiang for help with FACS sorting of PGCs; A. Inoue, S. Matoba and D. Cai for critical reading of the manuscript. This project is supported by NIH U01DK089565 (to Y.Z.). S.Y. is supported by a postdoctoral fellowship from the Japan Society for the Promotion of Science (JSPS). Y.Z. is an investigator of the Howard Hughes Medical Institute. NR 30 TC 67 Z9 71 U1 3 U2 65 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 19 PY 2013 VL 504 IS 7480 BP 460 EP + DI 10.1038/nature12805 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 273ZR UT WOS:000328575300057 PM 24291790 ER PT J AU Simon, MD Pinter, SF Fang, R Sarma, K Rutenberg-Schoenberg, M Bowman, SK Kesner, BA Maier, VK Kingston, RE Lee, JT AF Simon, Matthew D. Pinter, Stefan F. Fang, Rui Sarma, Kavitha Rutenberg-Schoenberg, Michael Bowman, Sarah K. Kesner, Barry A. Maier, Verena K. Kingston, Robert E. Lee, Jeannie T. TI High-resolution Xist binding maps reveal two-step spreading during X-chromosome inactivation SO NATURE LA English DT Article ID FACULTATIVE HETEROCHROMATIN; RNA; GENE; CHROMATIN; PROTEINS; LOCALIZATION; ANNOTATION; NUCLEUS; DOMAINS; DESIGN AB TheXist long noncodingRNA(lncRNA) is essential for X-chromosome inactivation (XCI), the process by which mammals compensate for unequal numbers of sex chromosomes(1-3). During XCI, Xist coats the future inactiveXchromosome(Xi)(4) and recruitsPolycomb repressive complex 2 (PRC2) to the X-inactivation centre (Xic)(5). How Xist spreads silencing on a 150-megabases scale is unclear. Here we generate high-resolution maps of Xist binding on the X chromosome across a developmental time course using CHART-seq. In female cells undergoing XCI de novo, Xist follows a two-step mechanism, initially targeting gene-rich islands before spreading to intervening gene-poor domains. Xist is depleted from genes that escape XCI but may concentrate near escapee boundaries. Xist binding is linearly proportional to PRC2 density and H3 lysine 27 trimethylation (H3K27me3), indicating co-migration of Xist and PRC2. Interestingly, when Xist is acutely stripped off from the Xi in post-XCI cells, Xist recovers quickly within both gene-rich and gene-poor domains on a timescale of hours instead of days, indicating a previously primed Xi chromatin state. We conclude that Xist spreading takes distinct stage-specific forms. During initial establishment, Xist follows a two-step mechanism, but during maintenance, Xist spreads rapidly to both gene-rich and gene-poor regions. C1 [Simon, Matthew D.; Pinter, Stefan F.; Sarma, Kavitha; Bowman, Sarah K.; Kesner, Barry A.; Maier, Verena K.; Kingston, Robert E.; Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Simon, Matthew D.; Pinter, Stefan F.; Sarma, Kavitha; Bowman, Sarah K.; Kesner, Barry A.; Maier, Verena K.; Kingston, Robert E.; Lee, Jeannie T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Simon, Matthew D.; Fang, Rui; Rutenberg-Schoenberg, Michael] Yale Univ, Dept Mol Biophys & Biochem, West Haven, CT 06516 USA. [Simon, Matthew D.; Fang, Rui; Rutenberg-Schoenberg, Michael] Yale Univ, Inst Chem Biol, West Haven, CT 06516 USA. [Pinter, Stefan F.; Sarma, Kavitha; Kesner, Barry A.; Maier, Verena K.; Lee, Jeannie T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Simon, MD (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM matthew.simon@yale.edu; kingston@molbio.mgh.harvard.edu; lee@molbio.mgh.harvard.edu OI Pinter, Stefan/0000-0003-4750-1403 FU Yale University; Deutsche Forschungsgemeinschaft; MGH Fund for Medical Discovery; National Institutes of Health [F32-GM090765, RO1-GM043901, RO1-GM090278] FX We thank J. Overton, I. Tikhonova and A. Lopez, and the MGH Bioinformatics Core. We also acknowledge funding from Yale University start-up funds to M. D. S., the Deutsche Forschungsgemeinschaft to S. F. P. and V. K. M., the MGH Fund for Medical Discovery to S. F. P., and the National Institutes of Health (grant F32-GM090765 to K. S., RO1-GM043901 to R. E. K., and RO1-GM090278 to J. T. L.). J. T. L. is an Investigator of the Howard Hughes Medical Institute. NR 43 TC 107 Z9 113 U1 3 U2 52 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 19 PY 2013 VL 504 IS 7480 BP 465 EP + DI 10.1038/nature12719 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 273ZR UT WOS:000328575300058 PM 24162848 ER PT J AU Kostin, A McGinty, D Szymusiak, R Alam, MN AF Kostin, A. McGinty, D. Szymusiak, R. Alam, M. N. TI SLEEP-WAKE AND DIURNAL MODULATION OF NITRIC OXIDE IN THE PERIFORNICAL-LATERAL HYPOTHALAMIC AREA: REAL-TIME DETECTION IN FREELY BEHAVING RATS SO NEUROSCIENCE LA English DT Article DE perifornical-lateral hypothalamus; nitric oxide; sleep-wakefulness; sleep deprivation; NO sensor; Nafion (R)-modified Platinum electrode ID EYE-MOVEMENT SLEEP; MEDIAL PREFRONTAL CORTEX; BASAL FOREBRAIN NEURONS; EXTRACELLULAR LEVELS; S-NITROSYLATION; CEREBRAL-CORTEX; NERVOUS-SYSTEM; OREXIN NEURONS; MOVING RATS; CYCLE AB Nitric oxide (NO) has been implicated in the regulation of sleep. The perifornical-lateral hypothalamic area (PF-LHA) is a key wake-promoting region and contains neurons that are active during behavioral or cortical activation. Recently, we found higher levels of NO metabolites (NO.), an indirect measure of NO levels, in the PF-LHA during prolonged waking (SD). However, NO is highly reactive and diffuses rapidly and the NO assay is not sensitive enough to detect rapid-changes in NO levels across spontaneous sleep-waking states. We used a novel Nafion -modified Platinum (NF-PT) electrode for real-time detection of NO levels in the PF-LHA across sleep-wake cycles, dark-light phases, and during SD. Sprague-Dawley male rats were surgically prepared for chronic sleep-wake recording and implantation of NF-PT electrode into the PF-LHA. Electroencephalogram (EEG), electromyogram (EMG), and electrochemical current generated by NF-PT electrode were continuously acquired for 5-7 days including one day with 3 h of SD. In the PF-LHA, NO levels exhibited -. waking > rapid eye movement (REM) > non-rapid eye movement (nonREM) sleep pattern (0.56 0.03 AM > 0.47 0.02 j.i.M 0.02 ELM; p < 0.01). NO levels were also higher during the darkas compared to the light-phase (0.53 0.03 RM vs. 0.44 0.02 p.M; p < 0.01). NO levels increased during 3 h of SD as compared to undisturbed control (0.58 0.04 ELM vs. 0.47 0.01 p.M; p < 0.05). The findings indicate that in the PF-LHA, NO is produced during behavioral or cortical activation. Since elevated levels of NO inhibits most of the PF-LHA neurons that are active during cortical activation, these findings support a hypothesis that NO produced in conjunction with the activation of PF-LHA neurons during waking/SD, inhibits the same neuronal population to promote sleep. Published by Elsevier Ltd. on behalf of IBRO. C1 [Kostin, A.; McGinty, D.; Szymusiak, R.; Alam, M. N.] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Sepulveda, CA 91343 USA. [McGinty, D.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Szymusiak, R.; Alam, M. N.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. RP Alam, MN (reprint author), VAGLAHS, Res Serv 151A3, 16111 Plummer St, North Hills, CA 91343 USA. EM noor@ucla.edu FU Medical Research Service; US Department of Veterans Affairs FX This work was supported by the Medical Research Service, US Department of Veterans Affairs. NR 60 TC 2 Z9 2 U1 0 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD DEC 19 PY 2013 VL 254 BP 275 EP 284 DI 10.1016/j.neuroscience.2013.09.022 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 255ZN UT WOS:000327279400024 PM 24056193 ER PT J AU Yazdanpanah, Y Perelman, J DiLorenzo, MA Alves, J Barros, H Mateus, C Pereira, J Mansinho, K Robine, M Park, JE Ross, EL Losina, E Walensky, RP Noubary, F Freedberg, KA Paltiel, AD AF Yazdanpanah, Yazdan Perelman, Julian DiLorenzo, Madeline A. Alves, Joana Barros, Henrique Mateus, Ceu Pereira, Joao Mansinho, Kamal Robine, Marion Park, Ji-Eun Ross, Eric L. Losina, Elena Walensky, Rochelle P. Noubary, Farzad Freedberg, Kenneth A. Paltiel, A. David TI Routine HIV Screening in Portugal: Clinical Impact and Cost-Effectiveness SO PLOS ONE LA English DT Article ID MULTIPLE VIROLOGICAL FAILURES; ACTIVE ANTIRETROVIRAL THERAPY; MODEL PARAMETER-ESTIMATION; OPPORTUNISTIC INFECTIONS; UNITED-STATES; SOUTH-AFRICA; VIRUS; TRANSMISSION; LOPINAVIR/RITONAVIR; UNCERTAINTY AB Objective: To compare the clinical outcomes and cost-effectiveness of routine HIV screening in Portugal to the current practice of targeted and on-demand screening. Design: We used Portuguese national clinical and economic data to conduct a model-based assessment. Methods: We compared current HIV detection practices to strategies of increasingly frequent routine HIV screening in Portuguese adults aged 18-69. We considered several subpopulations and geographic regions with varying levels of undetected HIV prevalence and incidence. Baseline inputs for the national case included undiagnosed HIV prevalence 0.16%, annual incidence 0.03%, mean population age 43 years, mean CD4 count at care initiation 292 cells/mu L, 63% HIV test acceptance, 78% linkage to care, and HIV rapid test cost (sic)6 under the proposed routine screening program. Outcomes included quality-adjusted survival, secondary HIV transmission, cost, and incremental cost-effectiveness. Results: One-time national HIV screening increased HIV-infected survival from 164.09 quality-adjusted life months (QALMs) to 166.83 QALMs compared to current practice and had an incremental cost-effectiveness ratio (ICER) of (sic)28,000 per quality-adjusted life year (QALY). Screening more frequently in higher-risk groups was cost-effective: for example screening annually in men who have sex with men or screening every three years in regions with higher incidence and prevalence produced ICERs of (sic)21,000/QALY and (sic)34,000/QALY, respectively. Conclusions: One-time HIV screening in the Portuguese national population will increase survival and is cost-effective by international standards. More frequent screening in higher-risk regions and subpopulations is also justified. Given Portugal's challenging economic priorities, we recommend prioritizing screening in higher-risk populations and geographic settings. C1 [Yazdanpanah, Yazdan] Univ Paris Diderot, Hop Bichat, Paris, France. [Yazdanpanah, Yazdan] Univ Paris 07, INSERM, U1137, ATIP Avenir Inserm Modelisat Aide Decis & Cout Ef, Paris, France. [Perelman, Julian; Alves, Joana; Mateus, Ceu; Pereira, Joao] Univ Nova Lisboa, Escola Nacl Saude Publ, P-1200 Lisbon, Portugal. [Barros, Henrique] Univ Porto, Inst Saude Publ, P-4100 Oporto, Portugal. [Mansinho, Kamal] Ctr Hosp Lisboa Ocidental, Lisbon, Portugal. [Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Losina, Elena; Walensky, Rochelle P.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Boston, MA USA. [DiLorenzo, Madeline A.; Robine, Marion; Park, Ji-Eun; Ross, Eric L.; Losina, Elena; Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [DiLorenzo, Madeline A.; Robine, Marion; Park, Ji-Eun; Ross, Eric L.; Losina, Elena; Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Losina, Elena; Walensky, Rochelle P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Losina, Elena; Walensky, Rochelle P.; Freedberg, Kenneth A.] Harvard Ctr AIDS Res, Boston, MA USA. [Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Noubary, Farzad] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA. [Noubary, Farzad] Tufts Univ, Tufts Clin & Translat Sci Inst, Boston, MA 02111 USA. [Paltiel, A. David] Yale Univ, Dept Hlth Policy & Management, Sch Publ Hlth, New Haven, CT USA. RP Yazdanpanah, Y (reprint author), Univ Paris Diderot, Hop Bichat, Paris, France. EM yazdan.yazdanpanah@bch.aphp.fr RI Pereira, Joao/A-8935-2010; Perelman, Julian/B-4350-2013; Mateus, Ceu/J-2554-2012; OI Pereira, Joao/0000-0002-7390-9755; Perelman, Julian/0000-0001-6634-9000; Mateus, Ceu/0000-0001-6219-219X; Walensky, Rochelle P./0000-0002-8795-379X; Barros, Henrique/0000-0003-4699-6571; Alves, Joana/0000-0002-5736-6519 FU Coordenacao Nacional para Infeccao VIH/SIDA; Agence Nationale de Recherches sur le SIDA et les hepatites virales (ANRS); National Institute of Allergy and Infectious Diseases [R37 AI42006]; National Institute of Mental Health [R01 MH065869]; National Institute on Drug Abuse [R01 DA015612] FX Sources of funding: Coordenacao Nacional para Infeccao VIH/SIDA, Agence Nationale de Recherches sur le SIDA et les hepatites virales (ANRS), National Institute of Allergy and Infectious Diseases (R37 AI42006), National Institute of Mental Health (R01 MH065869), and the National Institute on Drug Abuse (R01 DA015612). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 52 TC 8 Z9 8 U1 0 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 18 PY 2013 VL 8 IS 12 AR UNSP e84173 DI 10.1371/journal.pone.0084173 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 276HL UT WOS:000328740300131 PM 24367639 ER PT J AU Yasuda, H Park, E Yun, CH Sng, NJ Lucena-Araujo, AR Yeo, WL Huberman, MS Cohen, DW Nakayama, S Ishioka, K Yamaguchi, N Hanna, M Oxnard, GR Lathan, CS Moran, T Sequist, LV Chaft, JE Riely, GJ Arcila, ME Soo, RA Meyerson, M Eck, MJ Kobayashi, SS Costa, DB AF Yasuda, Hiroyuki Park, Eunyoung Yun, Cai-Hong Sng, Natasha J. Lucena-Araujo, Antonio R. Yeo, Wee-Lee Huberman, Mark S. Cohen, David W. Nakayama, Sohei Ishioka, Kota Yamaguchi, Norihiro Hanna, Megan Oxnard, Geoffrey R. Lathan, Christopher S. Moran, Teresa Sequist, Lecia V. Chaft, Jamie E. Riely, Gregory J. Arcila, Maria E. Soo, Ross A. Meyerson, Matthew Eck, Michael J. Kobayashi, Susumu S. Costa, Daniel B. TI Structural, Biochemical, and Clinical Characterization of Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion Mutations in Lung Cancer SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID TYROSINE KINASE INHIBITOR; PHASE-I; INCREASED SENSITIVITY; GENE-MUTATIONS; GEFITINIB; RESISTANCE; ERLOTINIB; MUTANTS; DOMAIN; ADENOCARCINOMAS AB Epidermal growth factor receptor (EGFR) gene mutations (G719X, exon 19 deletions/insertions, L858R, and L861Q) predict favorable responses to EGFR tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC). However, EGFR exon 20 insertion mutations (similar to 10% of all EGFR mutations) are generally associated with insensitivity to available TKIs (gefitinib, erlotinib, and afatinib). The basis of this primary resistance is poorly understood. We studied a broad subset of exon 20 insertion mutations, comparing in vitro TKI sensitivity with responses to gefitinib and erlotinib in NSCLC patients, and found that most are resistant to EGFR TKIs. The crystal structure of a representative TKI-insensitive mutant (D770_N771insNPG) reveals an unaltered adenosine triphosphate-binding pocket, and the inserted residues form a wedge at the end of the C helix that promotes the active kinase conformation. Unlike EGFR-L858R, D770_N771insNPG activates EGFR without increasing its affinity for EGFR TKIs. Unexpectedly, we find that EGFR-A763_Y764insFQEA is highly sensitive to EGFR TKIs in vitro, and patients whose NSCLCs harbor this mutation respond to erlotinib. Analysis of the A763_Y764insFQEA mutant indicates that the inserted residues shift the register of the C helix in the N-terminal direction, altering the structure in the region that is also affected by the TKI-sensitive EGFR-L858R. Our studies reveal intricate differences between EGFR mutations, their biology, and their response to EGFR TKIs. C1 [Yasuda, Hiroyuki; Sng, Natasha J.; Lucena-Araujo, Antonio R.; Yeo, Wee-Lee; Huberman, Mark S.; Cohen, David W.; Nakayama, Sohei; Yamaguchi, Norihiro; Kobayashi, Susumu S.; Costa, Daniel B.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Yasuda, Hiroyuki; Ishioka, Kota] Keio Univ, Sch Med, Tokyo 1608582, Japan. [Park, Eunyoung; Hanna, Megan; Oxnard, Geoffrey R.; Lathan, Christopher S.; Meyerson, Matthew; Eck, Michael J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Yun, Cai-Hong] Peking Univ, Hlth Sci Ctr, Beijing 100191, Peoples R China. [Hanna, Megan; Meyerson, Matthew] MIT, Broad Inst, Boston, MA 02142 USA. [Hanna, Megan; Meyerson, Matthew] Harvard Univ, Sch Med, Boston, MA 02142 USA. [Oxnard, Geoffrey R.; Lathan, Christopher S.; Meyerson, Matthew] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02215 USA. [Moran, Teresa; Sequist, Lecia V.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chaft, Jamie E.; Riely, Gregory J.; Arcila, Maria E.] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Soo, Ross A.] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117599, Singapore. [Soo, Ross A.] Natl Univ Singapore, Natl Univ Canc Inst, Singapore 117599, Singapore. RP Costa, DB (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. EM eck@red.dfci.harvard.edu; skobayas@bidmc.harvard.edu; dbcosta@bidmc.harvard.edu OI Chaft, Jamie/0000-0002-5838-9982; Costa, Daniel/0000-0002-0689-395X FU American Society of Clinical Oncology Conquer Cancer Foundation; Lung Cancer Foundation of America-International Association; American Cancer Society; American Lung Association; Uniting Against Lung Cancer grant; Saunders Family research fund; National Natural Science Foundation of China [31270769]; NIH [CA090578, CA116020, CA154303, CA126026, CA169259] FX This work was funded in part through fellowships from the American Society of Clinical Oncology Conquer Cancer Foundation (D. B. C.), a Lung Cancer Foundation of America-International Association for the Study of Lung Cancer grant (D. B. C.), American Cancer Society grant RSG 11-186 (D. B. C.), an American Lung Association grant (M. M.), a Uniting Against Lung Cancer grant (M. M.), a Saunders Family research fund (M. M.), National Natural Science Foundation of China grant 31270769 (C.-H.Y.), and NIH grants CA090578 (D. B. C., S. S. K., and M. M.), CA116020 (M.J.E. and M. M.), CA154303 (M.J.E.), CA126026 (S. S. K.), and CA169259 (S.S.K.). NR 70 TC 56 Z9 58 U1 1 U2 16 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD DEC 18 PY 2013 VL 5 IS 216 AR 216ra177 DI 10.1126/scitranslmed.3007205 PG 10 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 278MN UT WOS:000328894500004 PM 24353160 ER PT J AU Feres, F Costa, RA Abizaid, A Leon, MB Marin-Neto, JA Botelho, RV King, SB Negoita, M Liu, ML de Paula, JET Mangione, JA Meireles, GX Castello, HJ Nicolela, EL Perin, MA Devito, FS Labrunie, A Salvadori, D Gusmao, M Staico, R Costa, JR de Castro, JP Abizaid, AS Bhatt, DL AF Feres, Fausto Costa, Ricardo A. Abizaid, Alexandre Leon, Martin B. Marin-Neto, J. Antonio Botelho, Roberto V. King, Spencer B., III Negoita, Manuela Liu, Minglei de Paula, J. Eduardo T. Mangione, Jose A. Meireles, George X. Castello, Helio J., Jr. Nicolela, Eduardo L., Jr. Perin, Marco A. Devito, Fernando S. Labrunie, Andre Salvadori, Decio, Jr. Gusmao, Marcos Staico, Rodolfo Costa, J. Ribamar de Castro, Juliana P. Abizaid, Andrea S. Bhatt, Deepak L. CA OPTIMIZE Trial Investigators TI Three vs Twelve Months of Dual Antiplatelet Therapy After Zotarolimus-Eluting Stents The OPTIMIZE Randomized Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PERCUTANEOUS CORONARY INTERVENTION; OPTICAL COHERENCE TOMOGRAPHY; TERM CLINICAL-OUTCOMES; BARE-METAL STENT; CLOPIDOGREL THERAPY; NONCARDIAC SURGERY; DOUBLE-BLIND; FOLLOW-UP; IMPLANTATION; SAFETY AB IMPORTANCE The current recommendation is for at least 12 months of dual antiplatelet therapy after implantation of a drug-eluting stent. However, the optimal duration of dual antiplatelet therapy with specific types of drug-eluting stents remains unknown. OBJECTIVE To assess the clinical noninferiority of 3 months (short-term) vs 12 months (long-term) of dual antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI) with zotarolimus-eluting stents. DESIGN, SETTING, AND PATIENTS The OPTIMIZE trial was an open-label, active-controlled, 1:1 randomized noninferiority study including 3119 patients in 33 sites in Brazil between April 2010 and March 2012. Clinical follow-up was performed at 1, 3, 6, and 12 months. Eligible patients were those with stable coronary artery disease or history of low-risk acute coronary syndrome (ACS) undergoing PCI with zotarolimus-eluting stents. INTERVENTIONS After PCI with zotarolimus-eluting stents, patients were prescribed aspirin (100-200 mg daily) and clopidogrel (75 mg daily) for 3 months (n = 1563) or 12 months (n = 1556), unless contraindicated because of occurrence of an end point. MAIN OUTCOMES AND MEASURES The primary end point was net adverse clinical and cerebral events (NACCE; a composite of all-cause death, myocardial infarction [MI], stroke, or major bleeding); the expected event rate at 1 year was 9%, with a noninferiority margin of 2.7%. Secondary end points were major adverse cardiac events (MACE; a composite of all-cause death, MI, emergent coronary artery bypass graft surgery, or target lesion revascularization) and Academic Research Consortium definite or probable stent thrombosis. RESULTS NACCE occurred in 93 patients receiving short-term and 90 patients receiving long-term therapy (6.0% vs 5.8%, respectively; risk difference, 0.17 [95% CI, -1.52 to 1.86]; P = .002 for noninferiority). Kaplan-Meier estimates demonstrated MACE rates at 1 year of 8.3%(128) in the short-term group and 7.4%(114) in the long-term group (HR, 1.12 [95% CI, 0.87-1.45]). Between 91 and 360 days, no statistically significant association was observed for NACCE (39 [2.6%] vs 38 [2.6%] for the short-and long-term groups, respectively; HR, 1.03 [95% CI, 0.66-1.60]), MACE (78 [5.3%] vs 64 [4.3%]; HR, 1.22 [95% CI, 0.88-1.70]), or stent thrombosis (4 [0.3%] vs 1 [0.1%]; HR, 3.97 [95% CI, 0.44-35.49]). CONCLUSIONS AND RELEVANCE In patients with stable coronary artery disease or low-risk ACS treated with zotarolimus-eluting stents, 3 months of dual antiplatelet therapy was noninferior to 12 months for NACCE, without significantly increasing the risk of stent thrombosis. C1 [Feres, Fausto; Costa, Ricardo A.; Abizaid, Alexandre; Staico, Rodolfo; Costa, J. Ribamar] Inst Dante Pazzanese Cardiol, BR-04012180 Sao Paulo, Brazil. [Leon, Martin B.] Columbia Univ, Med Ctr, New York Presbyterian Med Ctr, New York, NY USA. [Leon, Martin B.] Cardiovasc Res Fdn, New York, NY USA. [Marin-Neto, J. Antonio] Univ Sao Paulo, Sao Paulo, Brazil. [Botelho, Roberto V.] Inst Coracao Triangulo Mineiro, Uberlandia, MG, Brazil. [King, Spencer B., III] St Josephs Med Grp, Atlanta, GA USA. [Negoita, Manuela; Liu, Minglei] Medtron CardioVasc, Santa Rosa, CA USA. [de Paula, J. Eduardo T.] Unicor Linhares, Linhares, Espirito Santo, Brazil. [Mangione, Jose A.; Salvadori, Decio, Jr.] Hosp Beneficencia Portuguesa Sao Paulo, Sao Paulo, Brazil. [Meireles, George X.] Hosp Publ Estadual Sao Paulo, Sao Paulo, Brazil. [Castello, Helio J., Jr.] Hosp Bandeirantes, Sao Paulo, Brazil. [Nicolela, Eduardo L., Jr.] Emcor Emergencias Coracao, Sao Paulo, Brazil. [Perin, Marco A.] Hosp Santa Marcelina, Sao Paulo, Brazil. [Devito, Fernando S.] Hosp Padre Albino FIPA, Sao Paulo, Brazil. [Labrunie, Andre] Santa Casa Misericordia Marilia, Sao Paulo, Brazil. [Gusmao, Marcos] Hosp Agamenon Magalhaes, Recife, PE, Brazil. [de Castro, Juliana P.; Abizaid, Andrea S.] Cardiovasc Res Ctr, Sao Paulo, Brazil. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA USA. [Bhatt, Deepak L.] Harvard Med Sch, Boston, MA USA. RP Feres, F (reprint author), Inst Dante Pazzanese Cardiol, Ave Dante Pazzanense 500, BR-04012180 Sao Paulo, Brazil. EM fferes@lee.dante.br RI Janella, Bruno/N-3148-2014; Perin, Marco/O-2309-2014 OI Janella, Bruno/0000-0003-1230-4653; FU independent clinical research organization-Cardiovascular Research Center, SA, Sao Paulo, Sao Paulo, Brazil; Medtronic Comercial Ltda, Sao Paulo, Sao Paulo, Brazil; Medtronic Comercial Ltda FX The OPTIMIZE trial was a physician-initiated trial cosponsored by an independent clinical research organization-Cardiovascular Research Center, SA, Sao Paulo, Sao Paulo, Brazil, and Medtronic Comercial Ltda, Sao Paulo, Sao Paulo, Brazil. The study was funded by Medtronic Comercial Ltda. NR 44 TC 217 Z9 228 U1 3 U2 24 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 18 PY 2013 VL 310 IS 23 BP 2510 EP 2522 DI 10.1001/jama.2013.282183 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 272ZZ UT WOS:000328503600021 PM 24177257 ER PT J AU Chen, HH Anstrom, KJ Givertz, MM Stevenson, LW Semigran, MJ Goldsmith, SR Bart, BA Bull, DA Stehlik, J LeWinter, MM Konstam, MA Huggins, GS Rouleau, JL O'Meara, E Tang, WHW Starling, RC Butler, J Deswal, A Felker, GM O'Connor, CM Bonita, RE Margulies, KB Cappola, TP Ofili, EO Mann, DL Davila-Roman, VG McNulty, SE Borlaug, BA Velazquez, EJ Lee, KL Shah, MR Hernandez, AF Braunwald, E Redfield, MM AF Chen, Horng H. Anstrom, Kevin J. Givertz, Michael M. Stevenson, Lynne W. Semigran, Marc J. Goldsmith, Steven R. Bart, Bradley A. Bull, David A. Stehlik, Josef LeWinter, Martin M. Konstam, Marvin A. Huggins, Gordon S. Rouleau, Jean L. O'Meara, Eileen Tang, W. H. Wilson Starling, Randall C. Butler, Javed Deswal, Anita Felker, G. Michael O'Connor, Christopher M. Bonita, Raphael E. Margulies, Kenneth B. Cappola, Thomas P. Ofili, Elizabeth O. Mann, Douglas L. Davila-Roman, Victor G. McNulty, Steven E. Borlaug, Barry A. Velazquez, Eric J. Lee, Kerry L. Shah, Monica R. Hernandez, Adrian F. Braunwald, Eugene Redfield, Margaret M. CA NHLBI Heart Failure Clin Res Netwo TI Low-Dose Dopamine or Low-Dose Nesiritide in Acute Heart Failure With Renal Dysfunction The ROSE Acute Heart Failure Randomized Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RELAX-AHF; SERELAXIN AB IMPORTANCE Small studies suggest that low-dose dopamine or low-dose nesiritide may enhance decongestion and preserve renal function in patients with acute heart failure and renal dysfunction; however, neither strategy has been rigorously tested. OBJECTIVE To test the 2 independent hypotheses that, compared with placebo, addition of low-dose dopamine (2 mu g/kg/min) or low-dose nesiritide (0.005 mu g/kg/min without bolus) to diuretic therapy will enhance decongestion and preserve renal function in patients with acute heart failure and renal dysfunction. DESIGN, SETTING, AND PARTICIPANTS Multicenter, double-blind, placebo-controlled clinical trial (Renal Optimization Strategies Evaluation [ROSE]) of 360 hospitalized patients with acute heart failure and renal dysfunction (estimated glomerular filtration rate of 15-60 mL/min/1.73 m(2)), randomized within 24 hours of admission. Enrollment occurred from September 2010 to March 2013 across 26 sites in North America. INTERVENTIONS Participants were randomized in an open, 1:1 allocation ratio to the dopamine or nesiritide strategy. Within each strategy, participants were randomized in a double-blind, 2:1 ratio to active treatment or placebo. The dopamine (n = 122) and nesiritide (n = 119) groups were independently compared with the pooled placebo group (n = 119). MAIN OUTCOMES AND MEASURES Coprimary end points included 72-hour cumulative urine volume (decongestion end point) and the change in serum cystatin C from enrollment to 72 hours (renal function end point). RESULTS Compared with placebo, low-dose dopamine had no significant effect on 72-hour cumulative urine volume (dopamine, 8524 mL; 95% CI, 7917-9131 vs placebo, 8296 mL; 95% CI, 7762-8830; difference, 229 mL; 95% CI, -714 to 1171 mL; P = .59) or on the change in cystatin C level (dopamine, 0.12 mg/L; 95% CI, 0.06-0.18 vs placebo, 0.11 mg/L; 95% CI, 0.06-0.16; difference, 0.01; 95% CI, -0.08 to 0.10; P = .72). Similarly, low-dose nesiritide had no significant effect on 72-hour cumulative urine volume (nesiritide, 8574 mL; 95% CI, 8014-9134 vs placebo, 8296 mL; 95% CI, 7762-8830; difference, 279 mL; 95% CI, -618 to 1176 mL; P = .49) or on the change in cystatin C level (nesiritide, 0.07 mg/L; 95% CI, 0.01-0.13 vs placebo, 0.11 mg/L; 95% CI, 0.06-0.16; difference, -0.04; 95% CI, -0.13 to 0.05; P = .36). Compared with placebo, there was no effect of low-dose dopamine or nesiritide on secondary end points reflective of decongestion, renal function, or clinical outcomes. CONCLUSION AND RELEVANCE In participants with acute heart failure and renal dysfunction, neither low-dose dopamine nor low-dose nesiritide enhanced decongestion or improved renal function when added to diuretic therapy. C1 [Chen, Horng H.; Borlaug, Barry A.; Redfield, Margaret M.] Mayo Clin, Rochester, MN 55905 USA. [Anstrom, Kevin J.; McNulty, Steven E.; Lee, Kerry L.; Hernandez, Adrian F.] Duke Clin Res Inst, Durham, NC 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. [Goldsmith, Steven R.; Bart, Bradley A.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. [Bull, David A.; Stehlik, Josef] Univ Utah, Salt Lake City, UT USA. [LeWinter, Martin M.] Univ Vermont, Burlington, VT 05405 USA. [Konstam, Marvin A.; Huggins, Gordon S.] Tufts Med Ctr, Boston, MA USA. [Rouleau, Jean L.; O'Meara, Eileen] Univ Montreal, Montreal, PQ, Canada. [Rouleau, Jean L.; O'Meara, Eileen] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Tang, W. H. Wilson; Starling, Randall C.] Cleveland Clin, Cleveland, OH 44106 USA. [Butler, Javed] Emory Univ, Atlanta, GA 30322 USA. [Deswal, Anita] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Deswal, Anita] Baylor Coll Med, Houston, TX USA. [Felker, G. Michael; O'Connor, Christopher M.; Velazquez, Eric J.] Duke Univ, Med Ctr, Durham, NC USA. [Felker, G. Michael; O'Connor, Christopher M.; Velazquez, Eric J.] Duke Heart Ctr, Durham, NC USA. [Bonita, Raphael E.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Margulies, Kenneth B.; Cappola, Thomas P.] Univ Penn, Philadelphia, PA 19104 USA. [Ofili, Elizabeth O.] Morehouse Sch Med, Atlanta, GA 30310 USA. [Mann, Douglas L.; Davila-Roman, Victor G.] Washington Univ, Sch Med, St Louis, MO USA. [Shah, Monica R.] NHLBI, Bethesda, MD 20892 USA. RP Chen, HH (reprint author), Mayo Clin Cardiovasc Res, Guggenheim 9,Mayo Clin,200 1st St SW, Rochester, MN 55905 USA. EM chen.horng@mayo.edu RI Hernandez, Adrian F./A-7818-2016; OI Patel, Ayan/0000-0003-1984-1400; Hernandez, Adrian F./0000-0003-3387-9616; Mann, Douglas /0000-0002-2516-0145 FU National Heart, Lung, and Blood Institute (NHLBI) [U10 HL084904, U01 HL084861, U10 HL110312, U109 HL110337, U01 HL084889, U01 HL084890, U01 HL084891, U10 HL110342, U10 HL110262, U01 HL084931, U10 HL110297, U10 HL110302, U10 HL110309, U10 HL110336, U10 HL110338]; National Center for Advancing Translational Sciences [UL1TR000454, UL1TR000135, UL1RR025008, UL1TR000439]; National Institute on Minority Health and Health Disparities [8 U54 MD007588] FX This work was supported by grants from the National Heart, Lung, and Blood Institute (NHLBI) (coordinating center: U10 HL084904; regional clinical centers: U01 HL084861, U10 HL110312, U109 HL110337, U01 HL084889, U01 HL084890, U01 HL084891, U10 HL110342, U10 HL110262, U01 HL084931, U10 HL110297, U10 HL110302, U10 HL110309, U10 HL110336, U10 HL110338). This work is also supported by the National Center for Advancing Translational Sciences (UL1TR000454, UL1TR000135, UL1RR025008, UL1TR000439) and the National Institute on Minority Health and Health Disparities (8 U54 MD007588). NR 26 TC 117 Z9 121 U1 2 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 18 PY 2013 VL 310 IS 23 BP 2533 EP 2543 DI 10.1001/jama.2013.282190 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 272ZZ UT WOS:000328503600023 PM 24247300 ER PT J AU Hoge, CW LeardMann, CA Boyko, EJ AF Hoge, Charles W. LeardMann, Cynthia A. Boyko, Edward J. TI Suicides Among Military Personnel Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID MILLENNIUM COHORT; US; COMBAT C1 [Hoge, Charles W.] Walter Reed Army Inst Res, Silver Spring, MD USA. [LeardMann, Cynthia A.] Naval Hlth Res Ctr, Deployment Hlth Res Dept, San Diego, CA 92106 USA. [Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. RP LeardMann, CA (reprint author), Naval Hlth Res Ctr, 140 Sylvester Rd, San Diego, CA 92106 USA. EM cynthia.leardmann@med.navy.mil NR 6 TC 2 Z9 2 U1 0 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 18 PY 2013 VL 310 IS 23 BP 2565 EP 2566 DI 10.1001/jama.2013.282701 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 272ZZ UT WOS:000328503600031 PM 24346997 ER PT J AU Schwab, JH Springfield, DS Raskin, KA Mankin, HJ Hornicek, FJ AF Schwab, Joseph H. Springfield, Dempsey S. Raskin, Kevin A. Mankin, Henry J. Hornicek, Francis J. TI What's New in Primary Malignant Musculoskeletal Tumors SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID SOFT-TISSUE SARCOMA; RADIATION-THERAPY; NEOADJUVANT CHEMOTHERAPY; EWING SARCOMA; BONE-TUMORS; OSTEOSARCOMA; SURVIVAL; CHONDROSARCOMA; EXTREMITY; CHORDOMA RP Schwab, JH (reprint author), Massachusetts Gen Hosp, Orthopaed Oncol Serv, 55 Fruit St, Boston, MA 02114 USA. EM jhschwab@partners.org NR 45 TC 1 Z9 1 U1 0 U2 3 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 EI 1535-1386 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD DEC 18 PY 2013 VL 95A IS 24 BP 2240 EP 2246 DI 10.2106/JBJS.M.01226 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 273IG UT WOS:000328527900016 PM 24352776 ER PT J AU Velazquez, ER Parmar, C Jermoumi, M Mak, RH van Baardwijk, A Fennessy, FM Lewis, JH De Ruysscher, D Kikinis, R Lambin, P Aerts, HJWL AF Velazquez, Emmanuel Rios Parmar, Chintan Jermoumi, Mohammed Mak, Raymond H. van Baardwijk, Angela Fennessy, Fiona M. Lewis, John H. De Ruysscher, Dirk Kikinis, Ron Lambin, Philippe Aerts, Hugo J. W. L. TI Volumetric CT-based segmentation of NSCLC using 3D-Slicer SO SCIENTIFIC REPORTS LA English DT Article ID CELL LUNG-CANCER; GROSS TUMOR VOLUME; OBSERVER VARIATION; INTEROBSERVER VARIABILITY; ENSEMBLE SEGMENTATION; PET-CT; DELINEATION; RADIOTHERAPY; DEFINITION; TISSUE AB Accurate volumetric assessment in non-small cell lung cancer (NSCLC) is critical for adequately informing treatments. In this study we assessed the clinical relevance of a semiautomatic computed tomography (CT)-based segmentation method using the competitive region-growing based algorithm, implemented in the free and public available 3D-Slicer software platform. We compared the 3D-Slicer segmented volumes by three independent observers, who segmented the primary tumour of 20 NSCLC patients twice, to manual slice-by-slice delineations of five physicians. Furthermore, we compared all tumour contours to the macroscopic diameter of the tumour in pathology, considered as the "gold standard". The 3D-Slicer segmented volumes demonstrated high agreement (overlap fractions > 0.90), lower volume variability (p = 0.0003) and smaller uncertainty areas (p = 0.0002), compared to manual slice-by-slice delineations. Furthermore, 3D-Slicer segmentations showed a strong correlation to pathology (r = 0.89, 95% CI, 0.81-0.94). Our results show that semiautomatic 3D-Slicer segmentations can be used for accurate contouring and are more stable than manual delineations. Therefore, 3D-Slicer can be employed as a starting point for treatment decisions or for high-throughput data mining research, such as Radiomics, where manual delineating often represent a time-consuming bottleneck. C1 [Velazquez, Emmanuel Rios; Parmar, Chintan; Jermoumi, Mohammed; Mak, Raymond H.; Lewis, John H.; Aerts, Hugo J. W. L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. [Velazquez, Emmanuel Rios; Parmar, Chintan; van Baardwijk, Angela; Lambin, Philippe; Aerts, Hugo J. W. L.] Maastricht Univ, GROW Res Inst, Dept Radiat Oncol MAASTRO, Maastricht, Netherlands. [Jermoumi, Mohammed] Univ Massachusetts, Lowell, MA USA. [De Ruysscher, Dirk] Katholieke Univ Leuven, Univ Hosp Leuven, Louvain, Belgium. [Fennessy, Fiona M.; Kikinis, Ron] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Velazquez, ER (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. EM Emmanuel_Rios@dfci.harvard.edu; Hugo_Aerts@dfci.harvard.edu RI Aerts, Hugo/P-6350-2015 OI Aerts, Hugo/0000-0002-2122-2003 FU National Institute of Health (NIH-USA) [U01 CA 143062-01]; CTMM framework (AIRFORCE project) [030-103]; EU; euroCAT (IVA Interreg); Kankeronderzoekfonds Limburg from the Health Foundation Limburg; Dutch Cancer Society [KWF UM 2011-5020, KWF UM 2009-4454]; QuIC-ConCePT project [115151] FX Authors acknowledge financial support from the National Institute of Health (NIH-USA U01 CA 143062-01, Radiomics of NSCLC), the CTMM framework (AIRFORCE project, grant 030-103), EU 6th and 7th framework program (METOXIA, EURECA, ARTFORCE), euroCAT (IVA Interreg - www.eurocat.info), Kankeronderzoekfonds Limburg from the Health Foundation Limburg and the Dutch Cancer Society (KWF UM 2011-5020, KWF UM 2009-4454). Authors also acknowledge financial support from the QuIC-ConCePT project (Grant Agreement No. 115151). NR 29 TC 21 Z9 26 U1 3 U2 29 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 18 PY 2013 VL 3 AR 3529 DI 10.1038/srep03529 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 273YH UT WOS:000328571700003 PM 24346241 ER PT J AU Brack, AS Hochedlinger, K AF Brack, Andrew S. Hochedlinger, Konrad TI ISSCR 2013: Back to Bean Town SO STEM CELL REPORTS LA English DT Article ID PLURIPOTENT STEM-CELLS; SUPER-ENHANCERS; EXPRESSION; LINEAGE; NEURONS; NICHES; NANOG C1 [Brack, Andrew S.; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Brack, Andrew S.; Hochedlinger, Konrad] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Brack, Andrew S.; Hochedlinger, Konrad] Harvard Stem Cell Inst, Cambridge, MA 02138 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. RP Brack, AS (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02114 USA. EM abrack@partners.org; khochedlinger@partners.org FU NIH [R01 AR060868, R01 AR061002, R01 HD058013, R01 DK96034] FX We thank Justine Zahowski and all highlight scientists for proofreading. This work was supported with grants from the NIH (R01 AR060868 and R01 AR061002 to A.S.B. and R01 HD058013 and R01 DK96034 to K.H). NR 18 TC 0 Z9 0 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2213-6711 J9 STEM CELL REP JI Stem Cell Rep. PD DEC 17 PY 2013 VL 1 IS 6 BP 479 EP 485 DI 10.1016/j.stemcr.2013.12.004 PG 7 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA AI1WY UT WOS:000336647100001 PM 25847520 ER PT J AU Nissenbaum, J Bar-Nur, O Ben-David, E Benvenisty, N AF Nissenbaum, Jonathan Bar-Nur, Ori Ben-David, Eyal Benvenisty, Nissim TI Global Indiscriminate Methylation in Cell-Specific Gene Promoters following Reprogramming into Human Induced Pluripotent Stem Cells SO STEM CELL REPORTS LA English DT Article ID DNA METHYLATION; EPIGENETIC MEMORY; DIFFERENTIATION; GENOME; FIBROBLASTS AB Molecular reprogramming of somatic cells into human induced pluripotent stem cells (iPSCs) is accompanied by extensive changes in gene expression patterns and epigenetic marks. To better understand the link between gene expression and DNA methylation, we have profiled human somatic cells from different embryonic cell types (endoderm, mesoderm, and parthenogenetic germ cells) and the iPSCs generated from them. We show that reprogramming is accompanied by extensive DNA methylation in CpG-poor promoters, sparing CpG-rich promoters. Intriguingly, methylation in CpG-poor promoters occurred not only in downregulated genes, but also in genes that are not expressed in the parental somatic cells or their respective iPSCs. These genes are predominantly tissue-specific genes of other cell types from different lineages. Our results suggest a role of DNA methylation in the silencing of the somatic cell identity by global nonspecific methylation of tissue-specific genes from all lineages, regardless of their expression in the parental somatic cells. C1 [Nissenbaum, Jonathan; Bar-Nur, Ori; Benvenisty, Nissim] Hebrew Univ Jerusalem, Inst Life Sci, Stem Cell Unit, IL-91905 Jerusalem, Israel. [Nissenbaum, Jonathan; Bar-Nur, Ori; Ben-David, Eyal; Benvenisty, Nissim] Hebrew Univ Jerusalem, Inst Life Sci, Dept Genet, IL-91905 Jerusalem, Israel. [Bar-Nur, Ori] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Bar-Nur, Ori] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. RP Benvenisty, N (reprint author), Hebrew Univ Jerusalem, Inst Life Sci, Stem Cell Unit, IL-91905 Jerusalem, Israel. EM nissimb@cc.huji.ac.il FU Legacy Heritage Biomedical Science Partnership Program of the Israel Science Foundation [269/12]; Juvenile Diabetes Research Foundation [1-2011-555]; Innovative Medicines Initiative [115439]; European Union; EFPIA FX The authors thank Uri Ben-david, Yonatan Stelzer, Daniel Ronen, Tomer Halevy, and Uri Weissbein for critically reading this manuscript and Tamar Golan-Lev for her assistance with the graphical design of the figures. We thank Yonatan Stelzer for his assistance with this work. N.B. is the Herbert Cohn Chair in Cancer Research. This research was partially supported by the Legacy Heritage Biomedical Science Partnership Program of the Israel Science Foundation (grant 269/12) and the Juvenile Diabetes Research Foundation (grant 1-2011-555). The research leading to these results has also received partial funding from the Innovative Medicines Initiative Joint Undertaking under grant agreement number 115439 (StemBANCC), resources of which are composed of financial contributions from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution. This publication reflects only the author's views and neither the IMI JU nor EFPIA nor the European Commission are liable for any use that may be made of the information contained therein. For more information, go to http://www.stembancc.org/. NR 27 TC 7 Z9 7 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2213-6711 J9 STEM CELL REP JI Stem Cell Rep. PD DEC 17 PY 2013 VL 1 IS 6 BP 509 EP 517 DI 10.1016/j.stemcr.2013.11.007 PG 9 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA AI1WY UT WOS:000336647100005 PM 24371806 ER PT J AU Wylie, KP Tanabe, J Martin, LF Wongngamnit, N Tregellas, JR AF Wylie, Korey P. Tanabe, Jody Martin, Laura F. Wongngamnit, Narin Tregellas, Jason R. TI Nicotine Increases Cerebellar Activity during Finger Tapping SO PLOS ONE LA English DT Article ID ACETYLCHOLINE-RECEPTOR; SCHIZOPHRENIC-PATIENTS; NONSMOKERS; ATTENTION; BRAIN; ACTIVATION; FMRI; METAANALYSIS; MOVEMENTS; SLICES AB Nicotine improves performance on several cognitive and sensorimotor tasks. The neuronal mechanisms associated with these changes in performance are, however, largely unknown. Functional magnetic resonance imaging (fMRI) was used to examine the effect of nicotine on neuronal response in nineteen healthy subjects while they performed an auditory-paced finger tapping task. Subjects performed the task, after receiving either a nicotine patch or placebo treatment, in a single blind, crossover design. Compared to placebo, nicotine treatment increased response in the cerebellar vermis. Increased vermal activity, in the absence of changes in other task-related regions suggests specificity in nicotine's effects. C1 [Wylie, Korey P.; Tanabe, Jody; Martin, Laura F.; Wongngamnit, Narin; Tregellas, Jason R.] Univ Colorado, Dept Psychiat, Aurora, CO 80309 USA. [Tanabe, Jody] Univ Colorado, Dept Radiol, Aurora, CO 80309 USA. [Tregellas, Jason R.] Denver Vet Affairs Med Ctr, Eastern Colorado Hlth Syst, Res Serv, Res Serv 151, Denver, CO USA. RP Tregellas, JR (reprint author), Univ Colorado, Dept Psychiat, Anschutz Med Campus, Aurora, CO 80309 USA. EM Jason.Tregellas@UCDenver.edu RI Tregellas, Jason/J-3637-2015 FU Veterans Administration Biomedical Laboratory and Clinical Science Research and Development Service; National Institutes of Mental Health [MH-086383]; Brain and Behavior Research Foundation; Blowitz-Ridgeway Foundation FX This work was supported by the Veterans Administration Biomedical Laboratory and Clinical Science Research and Development Service, the National Institutes of Mental Health grant MH-086383, the Brain and Behavior Research Foundation, and the Blowitz-Ridgeway Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 31 TC 3 Z9 5 U1 0 U2 13 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 2013 VL 8 IS 12 AR e84581 DI 10.1371/journal.pone.0084581 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 276GT UT WOS:000328737700102 PM 24358367 ER PT J AU Chen, HH Borlaug, BA Anstrom, KJ Felker, GM Givertz, MM Deswal, A Bart, BA Stevenson, LW Rouleau, JL O'Meara, E LeWinter, MM Bull, DA Stehlik, J Semigran, MJ Goldsmith, SR Ofili, EO O'Connor, CM Tang, WHW Starling, RC Butler, J Whellan, DJ Margulies, KB Cappola, TP Konstam, MA Mann, DL Davila-Roman, V McNulty, SE Velazquez, EJ Lee, KL Shah, MR Hernandez, AF Braunwald, E Redfield, MM AF Chen, Horng H. Borlaug, Barry A. Anstrom, Kevin J. Felker, G. M. Givertz, Michael M. Deswal, Anita Bart, Bradley A. Stevenson, Lynne W. Rouleau, Jean L. O'Meara, Eileen LeWinter, Martin M. Bull, David A. Stehlik, Josef Semigran, Marc J. Goldsmith, Steven R. Ofili, Elizabeth O. O'Connor, Christopher M. Tang, W. H. Wilson Starling, Randall C. Butler, Javed Whellan, David J. Margulies, Kenneth B. Cappola, Thomas P. Konstam, Marvin A. Mann, Douglas L. Davila-Roman, Victor McNulty, Steven E. Velazquez, Eric J. Lee, Kerry L. Shah, Monica R. Hernandez, Adrian F. Braunwald, Eugene Redfield, Magaret M. TI Renal Optimization Strategies Evaluation in Acute Heart Failure (ROSE AHF) Trial SO CIRCULATION LA English DT Meeting Abstract DE Acute heart failure; Renal function; Cardiovascular therapeutics; Catecholamines; Natriuretic peptide C1 [Chen, Horng H.; Borlaug, Barry A.; Redfield, Magaret M.] Mayo Clin, Rochester, MN USA. [Anstrom, Kevin J.; McNulty, Steven E.; Lee, Kerry L.; Hernandez, Adrian F.] Duke Clin Rsch Inst, Durham, NC USA. [Felker, G. M.] Duke Univ, Sch Med, Duke Heart Cntr, Durham, NC USA. [Givertz, Michael M.; Stevenson, Lynne W.; Braunwald, Eugene] Brigham & Womens Hosp, Boston, MA 02115 USA. [Deswal, Anita] Baylor Coll Med, Houston, TX 77030 USA. [Deswal, Anita] Baylor Clin, Houston, TX 77030 USA. [Bart, Bradley A.; Goldsmith, Steven R.] Univ Minnesota, Minneapolis, MN USA. [Rouleau, Jean L.; O'Meara, Eileen] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada. [LeWinter, Martin M.] Univ Vermont, Burlington, VT USA. [Bull, David A.; Stehlik, Josef] Univ Utah, Hlth Sci Cntr, Salt Lake City, UT USA. [Semigran, Marc J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ofili, Elizabeth O.] Morehouse Sch Med, Atlanta, GA 30310 USA. [O'Connor, Christopher M.; Velazquez, Eric J.] Duke Univ, Sch Med, Durham, NC USA. [O'Connor, Christopher M.; Velazquez, Eric J.] Duke Heart Cntr, Durham, NC USA. [Tang, W. H. Wilson; Starling, Randall C.] Cleveland Clin, Cleveland, OH 44106 USA. [Butler, Javed] Emory Univ, Atlanta, GA 30322 USA. [Whellan, David J.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Margulies, Kenneth B.; Cappola, Thomas P.] Univ Penn, Philadelphia, PA 19104 USA. [Konstam, Marvin A.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Mann, Douglas L.; Davila-Roman, Victor] Washington Univ, St Louis, MO USA. [Shah, Monica R.] NHLBI, Bethesda, MD 20892 USA. NR 0 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 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 17 PY 2013 VL 128 IS 24 BP 2707 EP 2708 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 271SB UT WOS:000328410800031 ER PT J AU Acker, MA Parides, MK Perrault, LP Moskowitz, AJ Voisine, P Smith, PK Gelijns, AC Hung, JW Blackstone, E Puskas, J Argenziano, M Gammie, JS Mack, M Ascheim, DD Bagiella, E Ferguson, TB Horvath, K Geller, NL Miller, MA Woo, JY D'Alessandro, DA Ailawadi, G Dagenais, F Gardner, TJ O'Gara, PT Michler, R Kron, IL AF Acker, Michael A. Parides, Michael K. Perrault, Louis P. Moskowitz, Alan J. Voisine, Pierre Smith, Peter K. Gelijns, Annetine C. Hung, Judy W. Blackstone, Eugene Puskas, John Argenziano, Michael Gammie, James S. Mack, Michael Ascheim, Deborah D. Bagiella, Emilia Ferguson, T. Bruce Horvath, Keith Geller, Nancy L. Miller, Marissa A. Woo, Joseph Y. D'Alessandro, David A. Ailawadi, Gorav Dagenais, Franois Gardner, Timothy J. O'Gara, Patrick T. Michler, Robert Kron, Irving L. TI Severe Ischemic Mitral Regurgitation: Is it Better to Repair or Replace the Valve? SO CIRCULATION LA English DT Meeting Abstract C1 [Acker, Michael A.] Hosp Univ Penn, Div Cardiovasc Surg, Philadelphia, PA 19104 USA. [Parides, Michael K.; Moskowitz, Alan J.; Gelijns, Annetine C.; Ascheim, Deborah D.; Bagiella, Emilia] Icahn Sch Med Mt Sinai, New York, NY USA. [Perrault, Louis P.] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Voisine, Pierre] Inst Univ Cardiol Quebec, Div Cardiac Surg, Quebec City, PQ, Canada. [Smith, Peter K.] Duke Univ, Durham, NC USA. [Hung, Judy W.] Massachusetts Gen Hosp, Echocardiog Core Lab, Boston, MA 02114 USA. [Blackstone, Eugene; Ailawadi, Gorav] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Puskas, John] Emory Univ Hosp Midtown, Atlanta, GA USA. [Argenziano, Michael] Columbia Univ, Med Cntr, New York, NY USA. [Gammie, James S.] Univ Maryland, Div Cardiac Surg, Baltimore, MD 21201 USA. [Mack, Michael] Baylor Res Inst, Plano, TX USA. [Ferguson, T. Bruce] ECU, East Carolina Heart Inst, Greenville, NC USA. [Horvath, Keith] NIH, Heart Cntr, Suburban Hosp, Bethesda, MD 20892 USA. [Geller, Nancy L.; Miller, Marissa A.] NHLBI, NIH, Bethesda, MD 20892 USA. [Woo, Joseph Y.] Hosp Univ Penn, Div Cardiothorac Surg, Philadelphia, PA 19104 USA. [D'Alessandro, David A.; Michler, Robert] Montefiore Einstein Heart Cntr, Bronx, NY USA. [Ailawadi, Gorav; Kron, Irving L.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Dagenais, Franois] Inst Univ Cardiol Quebec, Dept Cardiol, Quebec City, PQ, Canada. [Gardner, Timothy J.] Christiana Care Hlth Syst, Cardiovasc Med, Newark, DE USA. [O'Gara, Patrick T.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 17 PY 2013 VL 128 IS 24 BP 2708 EP 2708 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 271SB UT WOS:000328410800032 ER PT J AU Cooper, CJ Murphy, TP Cutlip, DE D'Agostino, R Jamerson, K Matsumoto, AH Jaff, MR Michael, S Solomon, S Cohen, D Tuttle, KR Rundback, JH Shapiro, JI Reid, D Henrich, W Dworklin, L AF Cooper, Christopher J. Murphy, Timothy P. Cutlip, Donald E. D'Agostino, Ralph Jamerson, Kenneth Matsumoto, Alan H. Jaff, Michael R. Michael, Steffes Solomon, Scott Cohen, David Tuttle, Katherine R. Rundback, John H. Shapiro, Joseph I. Reid, Diane Henrich, William Dworklin, Lance TI A Randomized Multicenter Clinical Trial of Renal Artery Stenting in Preventing Cardiovascular and Renal Events: Results of the CORAL Study SO CIRCULATION LA English DT Meeting Abstract DE Renal circulation; Stent; Clinical trials C1 [Cooper, Christopher J.] Univ Toledo, Toledo, OH 43606 USA. [Murphy, Timothy P.; Dworklin, Lance] Brown Univ, Rhode Isl Hosp, Sch Med, Providence, RI 02903 USA. [Cutlip, Donald E.] Harvard Univ, Sch Med, Beth Israel Deaconess Hosp, Boston, MA 02215 USA. [D'Agostino, Ralph] Boston Univ, Boston, MA 02215 USA. [Jamerson, Kenneth] Univ Michigan, Med Cntr, Ann Arbor, MI 48109 USA. [Matsumoto, Alan H.] Univ Virginia, Charlottesville, VA USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Michael, Steffes] Univ Minnesota, Minneapolis, MN USA. [Solomon, Scott] Brigham & Womens Hosp, Noninvas Cardiac Lab, Boston, MA 02115 USA. [Cohen, David] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Tuttle, Katherine R.] Providence Med Rsch Cntr, Spokane, WA USA. [Rundback, John H.] Inst Clin Rsch, Intervent Inst, Teaneck, NJ USA. [Shapiro, Joseph I.] Marshall Univ, Huntington, WV USA. [Reid, Diane] NHLBI, Div Heart & Vasc Dis, Bethesda, MD 20892 USA. [Henrich, William] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 17 PY 2013 VL 128 IS 24 BP 2710 EP 2710 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 271SB UT WOS:000328410800037 ER PT J AU Arora, P Harrell, F Carney, E Guanaga, D Wolf, M Sabatine, M Song, YN Russell, JY Karol, C Torre, M Cheng, SS Zaleski, A Panza, G Azzahir, A Strachan, SM Jones, R Jones, S Reinstein, A O'Neill, DC Swales, H Plotnikoff, G Dusek, J Newton-Cheh, C Wang, TJ AF Arora, Pankaj Harrell, Frank Carney, Erin Guanaga, Derek Wolf, Myles Sabatine, Marc Song, Yanna Russell, Joseph Y. Karol, Courtney Torre, Michael Cheng, Susan Zaleski, Amanda Panza, Gregory Azzahir, Atum Strachan, Semerit M. Jones, Robert Jones, Sarah Reinstein, Adam O'Neill, Dillon C. Swales, Heather Plotnikoff, Gregory Dusek, Jeffery Newton-Cheh, Christopher Wang, Thomas J. TI Daylight: Vitamin D Therapy in Individuals at High Risk of Hypertension SO CIRCULATION LA English DT Meeting Abstract DE Blood pressure; Vitamins; Hypertension; Clinical trials; Population science C1 [Arora, Pankaj] Univ Alabama Birmingham, Cardiol Div, Birmingham, AL USA. [Harrell, Frank; Song, Yanna] Vanderbilt Univ, Nashville, TN 37235 USA. [Carney, Erin; Guanaga, Derek; Russell, Joseph Y.; Karol, Courtney; Torre, Michael; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiol Div, Boston, MA 02114 USA. [Wolf, Myles] Univ Miami Miller Sch Med, Div Nephrol & Hypertens, Miami, FL USA. [Sabatine, Marc; Cheng, Susan] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. [Zaleski, Amanda; Panza, Gregory; Swales, Heather] Hartford Hosp, Cardiol Div, Hartford, CT 06115 USA. [Azzahir, Atum] Cultural Wellness Cntr, Cardiol Div, Minneapolis, MN USA. [Strachan, Semerit M.] Cultural Wellness Cntr, Integrat Hlth Rsch Cntr, Minneapolis, MN USA. [Jones, Robert; Jones, Sarah; Reinstein, Adam; Plotnikoff, Gregory; Dusek, Jeffery] Abbott NW Hosp, Integrat Hlth Rsch Cntr, Minneapolis, MN 55407 USA. [O'Neill, Dillon C.; Wang, Thomas J.] Vanderbilt Univ, Div Cardiol, Nashville, TN 37232 USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 17 PY 2013 VL 128 IS 24 BP 2716 EP 2717 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 271SB UT WOS:000328410800052 ER PT J AU Koren, MJ Giugliano, RP Raal, F Sullivan, D Bolognese, M Langslet, G Civeira, F Scott, R Somaratne, R Nelson, P Liu, T Wasserman, SM Sabatine, MS AF Koren, Michael J. Giugliano, Robert P. Raal, Frederick Sullivan, David Bolognese, Michael Langslet, Gisle Civeira, Fernando Scott, Rob Somaratne, Ransi Nelson, Patric Liu, Thomas Wasserman, Scott M. Sabatine, Marc S. TI Randomized Comparison of the Safety, Tolerability, and Efficacy of Long-term Administration of AMG 145 versus Standard of Care in 1104 Patients: 52-week Results from the OSLER Study SO CIRCULATION LA English DT Meeting Abstract DE Hyperlipidemia; Clinical trials; Monoclonal antibodies; Outcomes; Transesophageal echocardiography C1 [Koren, Michael J.] Jacksonville Cntr Clin Rsch, Jacksonville, FL USA. [Giugliano, Robert P.; Sabatine, Marc S.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Raal, Frederick] Univ Witwatersrand Med Sch, Dept Med, Johannesburg, South Africa. [Sullivan, David] Royal Prince Alfred Hosp, Dept Clin Biochem, Camperdown, NSW 2050, Australia. [Bolognese, Michael] Bethesda Hlth Rsch Cntr, Bethesda, MD USA. [Langslet, Gisle] Oslo Univ Hosp, Lipid Clin, Oslo, Norway. [Civeira, Fernando] Hosp Univ Miguel Servet, Lipid Clin, Zaragoza, Spain. [Scott, Rob; Somaratne, Ransi; Nelson, Patric; Wasserman, Scott M.] Amgen Inc, Global Dev, Thousand Oaks, CA 91320 USA. [Liu, Thomas] Amgen Inc, Biostat, Thousand Oaks, CA 91320 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 17 PY 2013 VL 128 IS 24 BP 2717 EP 2718 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 271SB UT WOS:000328410800054 ER PT J AU Iwataki, M Kim, YJ Sun, BJ Jang, JY Takeuchi, M Kuwaki, H Otani, K Haruki, N Yoshitani, H Levine, RA Song, JK Otsuji, Y AF Iwataki, Mai Kim, Yun-Jeong Sun, Byung-Joo Jang, Jeong-Yoon Takeuchi, Masaaki Kuwaki, Hiroshi Otani, Kyoko Haruki, Nobuhiko Yoshitani, Hidetoshi Levine, Robert A. Song, Jae-Kwan Otsuji, Yutaka TI Different Characteristics of Chronic Heart Failure due to Pump Failure and Bradyarrythmia SO CIRCULATION LA English DT Meeting Abstract DE Echocardiography C1 [Iwataki, Mai; Takeuchi, Masaaki; Kuwaki, Hiroshi; Otani, Kyoko; Haruki, Nobuhiko; Yoshitani, Hidetoshi; Otsuji, Yutaka] Univ Occupat & Environm Hlth, Kitakyushu, Fukuoka 807, Japan. [Kim, Yun-Jeong; Sun, Byung-Joo; Jang, Jeong-Yoon; Song, Jae-Kwan] Asan Med Ctr, Seoul, South Korea. [Levine, Robert A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 17 PY 2013 VL 128 IS 24 BP 2720 EP 2721 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 271SB UT WOS:000328410800063 ER PT J AU Nallamothu, BK Spertus, JA Lansky, AJ Cohen, DJ Jones, PG Kureshi, F Dehmer, GJ Drozda, JP Walsh, MN Brush, JE Koenig, GC Waites, TF Gantt, DS Kichura, G Chazal, RA O'Brien, PK Valentine, CM Rumsfeld, JS Reiber, JHC Elmore, JG Krumholz, RA Weaver, WD Krumholz, HM AF Nallamothu, Brahmajee K. Spertus, John A. Lansky, Alexandra J. Cohen, David J. Jones, Philip G. Kureshi, Faraz Dehmer, Gregory J. Drozda, Joseph P., Jr. Walsh, Mary Norine Brush, John E., Jr. Koenig, Gerald C. Waites, Thad F. Gantt, D. Scott Kichura, George Chazal, Richard A. O'Brien, Peter K. Valentine, C. Michael Rumsfeld, John S. Reiber, Johan H. C. Elmore, Joann G. Krumholz, Richard A. Weaver, W. Douglas Krumholz, Harlan M. TI Response to Letters Regarding Article, "Comparison of Clinical Interpretation With Visual Assessment and Quantitative Coronary Angiography in Patients Undergoing Percutaneous Coronary Intervention in Contemporary Practice: The Assessing Angiography (A2) Project" SO CIRCULATION LA English DT Letter ID FLOW RESERVE C1 [Nallamothu, Brahmajee K.] Ann Arbor VA Ctr Clin Management & Res, Ann Arbor, MI USA. [Spertus, John A.; Cohen, David J.; Jones, Philip G.; Kureshi, Faraz] St Lukes Mid Amer Heart Inst, Kansas City, MO USA. [Lansky, Alexandra J.] Yale Univ, Sch Med, New Haven, CT USA. [Dehmer, Gregory J.; Gantt, D. Scott] Texas A&M Univ, Coll Med, Hlth Sci Ctr, Temple, TX 76508 USA. [Drozda, Joseph P., Jr.] Mercy Hlth, St Louis, MO USA. [Walsh, Mary Norine] St Vincent Heart Ctr Indiana, Indianapolis, IN USA. [Brush, John E., Jr.] Sentara Cardiovasc Res Inst, Norfolk, VA USA. [Koenig, Gerald C.; Weaver, W. Douglas] Henry Ford Hlth Syst, Detroit, MI USA. [Waites, Thad F.] Forrest Gen, Hattiesburg, MS USA. [Kichura, George] Mercy Hlth Syst, St Louis, MO USA. [Chazal, Richard A.] Lee Mem Hlth Syst, Ft Myers, FL USA. [O'Brien, Peter K.; Valentine, C. Michael] Centra Lynchburg Gen Hosp, Lynchburg, VA USA. [Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA. [Reiber, Johan H. C.] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands. [Elmore, Joann G.] Univ Washington, Dept Med, Seattle, WA USA. [Krumholz, Richard A.] ImageCor, Bradenton, FL USA. [Krumholz, Harlan M.] Ctr Outcomes Res & Evaluat, New Haven, CT USA. RP Nallamothu, BK (reprint author), Ann Arbor VA Ctr Clin Management & Res, Ann Arbor, MI USA. NR 5 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 17 PY 2013 VL 128 IS 24 BP E463 EP E464 DI 10.1161/CIRCULATIONAHA.113.005507 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 271SB UT WOS:000328410800008 PM 24344070 ER PT J AU Chan, PS Rao, SV Bhatt, DL Rumsfeld, JS Gurm, HS Nallamothu, BK Cavender, MA Kennedy, KF Spertus, JA AF Chan, Paul S. Rao, Sunil V. Bhatt, Deepak L. Rumsfeld, John S. Gurm, Hitinder S. Nallamothu, Brahmajee K. Cavender, Matthew A. Kennedy, Kevin F. Spertus, John A. TI Patient and Hospital Characteristics Associated With Inappropriate Percutaneous Coronary Interventions SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE disparities; overuse; PCI; quality of care ID APPROPRIATENESS; REVASCULARIZATION AB Objectives This study sought to examine whether rates of inappropriate percutaneous coronary intervention (PCI) differ by demographic characteristics and insurance status. Background Prior studies have found that blacks, women, and those who have public or no health insurance are less likely to undergo PCI. Whether this reflects potential overuse in whites, men, and privately insured patients, in addition to underuse in disadvantaged populations, is unknown. Methods Within the National Cardiovascular Data Registry CathPCI Registry, we identified 221,254 nonacute PCIs performed between July 2009 and March 2011. The appropriateness of PCI was determined using the Appropriate Use Criteria for coronary revascularization. Multivariable hierarchical regression was used to evaluate the association between patient demographics and insurance status and inappropriate PCI, as defined by the Appropriate Use Criteria. Results Of 211,254 nonacute PCIs, 25,749 (12.2%) were classified as inappropriate. After multivariable adjustment, men (adjusted odd ratio [OR]: 1.08 [95% CI: 1.05 to 1.11]; p < 0.001) and whites (adjusted OR: 1.09 [95% CI: 1.05 to 1.14]; p < 0.001) were more likely to undergo an inappropriate PCI in comparison with women and nonwhites. Compared with privately insured patients, those who had Medicare (adjusted OR: 0.85 [95% CI: 0.83 to 0.88]), other public insurance (adjusted OR: 0.78 [95% CI: 0.73 to 0.83]), and no insurance (adjusted OR: 0.56 [95% CI: 0.50 to 0.61]) were less likely to undergo an inappropriate PCI (p < 0.001). In addition, compared with urban hospitals, those admitted at rural hospitals were less likely to undergo inappropriate PCI, whereas those at suburban hospitals were more likely. Conclusions For nonacute indications, PCIs categorized as inappropriate were more commonly performed in men, whites, and those who had private insurance. Higher rates of PCI in these patient populations may, in part, be due to procedural overuse. (C) 2013 by the American College of Cardiology Foundation C1 [Chan, Paul S.; Kennedy, Kevin F.; Spertus, John A.] St Lukes Mid Amer Heart Inst, Kansas City, MO USA. [Chan, Paul S.; Spertus, John A.] Univ Missouri, Kansas City, MO 64110 USA. [Rao, Sunil V.] Duke Clin Res Inst, Durham, NC USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. [Bhatt, Deepak L.; Cavender, Matthew A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bhatt, Deepak L.; Cavender, Matthew A.] Harvard Univ, Sch Med, Boston, MA USA. [Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA. [Gurm, Hitinder S.; Nallamothu, Brahmajee K.] Univ Michigan, Ann Arbor, MI 48109 USA. [Nallamothu, Brahmajee K.] VA Ann Arbor Healthcare Syst, VA Hlth Serv Res & Dev Ctr Excellence, Ann Arbor, MI USA. [Nallamothu, Brahmajee K.] Ctr Healthcare Outcomes & Policy, Ann Arbor, MI USA. RP Chan, PS (reprint author), Mid Amer Heart Inst, 4401 Wornall Rd,5th Floor, Kansas City, MO 64111 USA. EM pchan@cc-pc.com OI Gurm, Hitinder/0000-0002-1646-0218 FU U.S. National Institute of Health; American College of Cardiology Foundation's National Cardiovascular Data Registry; National Heart, Lung, and Blood Institute [K23HL102224]; Amarin; AstraZeneca; Bristol-Myers Squibb; Eisai; Ethicon; Medtronic; Sanofi Aventis; Medicines Company; FlowCo; PLx Pharma; Takeda; Brigham and Women's Hospital from AstraZeneca; American College of Cardiology Foundation; National Heart, Lung, and Blood Institute; American Heart Association; Gilead; Lilly; Amorcyte; EvaHeart FX The underlying research reported in the article was funded by the U.S. National Institute of Health and by the American College of Cardiology Foundation's National Cardiovascular Data Registry. The views expressed in this manuscript represent those of the authors, and do not necessarily represent the official views of the NCDR or its associated professional societies identified at www.ncdr.com/. Dr. Chan has received a Career Development Grant Award (K23HL102224) from the National Heart, Lung, and Blood Institute, has an industry relationship with the American Heart Association and Optum Rx as a consultant, and is on the steering committee of Johnson and Johnson. Dr. Bhatt is a member of the Advisory Board of Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; is a member of the Board of Directors of the Boston VA Research Institute and the Society of Chest Pain Centers; is Chair of the American Heart Association Get With The Guidelines Science Subcommittee; has received honoraria from the American College of Cardiology (as Editor of Clinical Trials, Cardiosource), Belvoir Publications (as Editor in Chief of Harvard Heart Letter), Duke Clinical Research Institute (on the clinical trial steering and data monitoring committees), Population Health Research Institute (on the clinical trial steering committee), Slack Publications (as Chief Medical Editor of Cardiology Today Intervention), and WebMD (on the CME steering committees), is Senior Associate Editor of the Journal of Invasive Cardiology; has received research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, and The Medicines Company; and has received unfunded research from FlowCo, PLx Pharma, and Takeda. Dr. Cavender has received research grants through Brigham and Women's Hospital from AstraZeneca and Bristol-Myers Squibb. Dr. Spertus is the principal investigator of a contract from the American College of Cardiology Foundation to analyze the National Cardiovascular Data Registry (NCDR) databases; serves on the Scientific Advisory Board for United Healthcare, and has consulted for Gilead, Genentech, Amgen, and St. Jude; has received research grants from National Heart, Lung, and Blood Institute, American Heart Association, Gilead, Lilly, Amorcyte, and EvaHeart; has an equity position in Health Outcomes Sciences; and owns the copyright to the Seattle Angina Questionnaire, Kansas City Cardiomyopathy Questionnaire, and the Peripheral Artery Questionnaire. Dr. Rumsfeld is Chief Science Officer for the NCDR. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 18 TC 11 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 17 PY 2013 VL 62 IS 24 BP 2274 EP 2281 DI 10.1016/j.jacc.2013.07.086 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 267CG UT WOS:000328073300003 PM 24055743 ER PT J AU Joynt, KE AF Joynt, Karen E. TI Trade-Offs in Appropriateness of Percutaneous Coronary Intervention SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE appropriateness; PCI; predictors ID ACUTE MYOCARDIAL-INFARCTION; CARDIAC REVASCULARIZATION; RACIAL-DIFFERENCES; GENDER; RATES; CARE; DISPARITIES; HOSPITALS; MORTALITY; OUTCOMES C1 [Joynt, Karen E.] Brigham & Womens Hosp, Div Cardiovasc Med, Dept Internal Med, Boston, MA 02115 USA. [Joynt, Karen E.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Joynt, Karen E.] VA Boston Healthcare Syst, Cardiol Div, Boston, MA USA. RP Joynt, KE (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM kjoynt@partners.org NR 16 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 17 PY 2013 VL 62 IS 24 BP 2282 EP 2283 DI 10.1016/j.jacc.2013.08.1618 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 267CG UT WOS:000328073300004 PM 24055745 ER PT J AU Liu, Y Shoji-Kawata, S Sumpter, RM Wei, YJ Ginet, V Zhang, LY Posner, B Tran, KA Green, DR Xavier, RJ Shaw, SY Clarke, PGH Puyal, J Levine, B AF Liu, Yang Shoji-Kawata, Sanae Sumpter, Rhea M., Jr. Wei, Yongjie Ginet, Vanessa Zhang, Liying Posner, Bruce Tran, Khoa A. Green, Douglas R. Xavier, Ramnik J. Shaw, Stanley Y. Clarke, Peter G. H. Puyal, Julien Levine, Beth TI Autosis is a Na+,K+-ATPase-regulated form of cell death triggered by autophagy-inducing peptides, starvation, and hypoxia-ischemia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CARDIAC-GLYCOSIDES; ISCHEMIA/REPERFUSION INJURY; BECLIN 1; MECHANISMS; NEUROPROTECTION; APOPTOSIS; DISEASE; PROTEIN; STROKE; ATPASE AB A long-standing controversy is whether autophagy is a bona fide cause of mammalian cell death. We used a cell-penetrating autophagy- inducing peptide, Tat-Beclin 1, derived from the autophagy protein Beclin 1, to investigate whether high levels of autophagy result in cell death by autophagy. Here we show that Tat-Beclin 1 induces dose-dependent death that is blocked by pharmacological or genetic inhibition of autophagy, but not of apoptosis or necroptosis. This death, termed "autosis," has unique morphological features, including increased autophagosomes/autolysosomes and nuclear convolution at early stages, and focal swelling of the perinuclear space at late stages. We also observed autotic death in cells during stress conditions, including in a subpopulation of nutrient-starved cells in vitro and in hippocampal neurons of neonatal rats subjected to cerebral hypoxia-ischemia in vivo. A chemical screen of similar to 5,000 known bioactive compounds revealed that cardiac glycosides, antagonists of Na+, K+-ATPase, inhibit autotic cell death in vitro and in vivo. Furthermore, genetic knockdown of the Na+, K+-ATPase alpha 1 subunit blocks peptide and starvation-induced autosis in vitro. Thus, we have identified a unique form of autophagy-dependent cell death, a Food and Drug Administration-approved class of compounds that inhibit such death, and a crucial role for Na+, K+-ATPase in its regulation. These findings have implications for understanding how cells die during certain stress conditions and how such cell death might be prevented. C1 [Liu, Yang; Shoji-Kawata, Sanae; Sumpter, Rhea M., Jr.; Wei, Yongjie; Levine, Beth] Univ Texas SW Med Ctr Dallas, Ctr Autophagy Res, Dallas, TX 75390 USA. [Liu, Yang; Shoji-Kawata, Sanae; Sumpter, Rhea M., Jr.; Wei, Yongjie; Levine, Beth] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Zhang, Liying; Posner, Bruce] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA. [Levine, Beth] Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA. [Wei, Yongjie; Levine, Beth] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA. [Ginet, Vanessa; Clarke, Peter G. H.; Puyal, Julien] Univ Lausanne, Dept Fundamental Neurosci, CH-1005 Lausanne, Switzerland. [Tran, Khoa A.; Shaw, Stanley Y.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Xavier, Ramnik J.; Shaw, Stanley Y.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Green, Douglas R.] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA. RP Puyal, J (reprint author), Univ Lausanne, Dept Fundamental Neurosci, CH-1005 Lausanne, Switzerland. EM JulienPierre.Puyal@unil.ch; beth.levine@utsouthwestern.edu RI Zhang, Liying/A-3163-2014 FU National Institutes of Health [U54 AI057156, RO1 CA109618, RO1 A140646, HHSN268201000044C, PO1 CA95471, P30 CA142543]; Swiss National Science Foundation [310030-130769] FX We thank Noboru Mizushima, Qiong Shi, Herbert Virgin, Xiaodong Wang, Qing Zhong, and Sandra Zinkel for providing critical reagents; Shuguang Wei for assistance with high-throughput screening; Beatriz Fontoura for helpful discussions; Zhongju Zou for technical support; Haley Harrington for assistance with manuscript preparation; the University of Texas (UT) Southwestern Live Cell Imaging Facility; and the Electron Microscopy Facility of the University of Lausanne. This work was supported by National Institutes of Health Grants U54 AI057156 and RO1 CA109618 (to B. L.), RO1 A140646 (to D. R. G.); Contract HHSN268201000044C (to S. Y. S.), PO1 CA95471 (to Dr. Steven McKnight, UT Southwestern Medical Center), and P30 CA142543 (to the UT Southwestern Simmons Cancer Center); and by the Swiss National Science Foundation Grant 310030-130769 (to J. P.). NR 35 TC 95 Z9 97 U1 0 U2 30 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 17 PY 2013 VL 110 IS 51 BP 20364 EP 20371 DI 10.1073/pnas.1319661110 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 273PR UT WOS:000328548600021 PM 24277826 ER PT J AU Kulkarni, S Qi, Y O'hUigin, C Pereyra, F Ramsuran, V McLaren, P Fellay, J Nelson, G Chen, HY Liao, W Bass, S Apps, R Gao, XJ Yuki, Y Lied, A Ganesan, A Hunt, PW Deeks, SG Wolinsky, S Walker, BD Carrington, M AF Kulkarni, Smita Qi, Ying O'hUigin, Colm Pereyra, Florencia Ramsuran, Veron McLaren, Paul Fellay, Jacques Nelson, George Chen, Haoyan Liao, Wilson Bass, Sara Apps, Richard Gao, Xiaojiang Yuki, Yuko Lied, Alexandra Ganesan, Anuradha Hunt, Peter W. Deeks, Steven G. Wolinsky, Steven Walker, Bruce D. Carrington, Mary TI Genetic interplay between HLA-C and MIR148A in HIV control and Crohn disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GENOME-WIDE ASSOCIATION; CELL-SURFACE EXPRESSION; HEAVY-CHAIN; DETERMINANTS; RNA; POLYMORPHISM; INFECTION; COHORT; NEF AB Variation in the 3' untranslated region (3'UTR) of the HLA-C locus determines binding of the microRNA Hsa-miR-148a, resulting in lower cell surface expression of alleles that bind miR-148a relative to those alleles that escape its binding. The HLA-C 3'UTR variant was shown to associate with HIV control, but like the vast majority of disease associations in a region dense with causal candidates, a direct effect of HLA-C expression level on HIV control was not proven. We demonstrate that a MIR148A insertion/deletion polymorphism associates with its own expression levels, affecting the extent to which HLA-C is down-regulated, the level of HIV control, and the risk of Crohn disease only among those carrying an intact miR-148a binding site in the HLA-C 3'UTR. These data illustrate a direct effect of HLA-C expression level on HIV control that cannot be attributed to other HLA loci in linkage disequilibrium with HLA-C and highlight the rich complexity of genetic interactions in human disease. C1 [Kulkarni, Smita; Qi, Ying; O'hUigin, Colm; Bass, Sara; Apps, Richard; Gao, Xiaojiang; Yuki, Yuko; Carrington, Mary] Frederick Natl Lab Canc Res, Sci Applicat Int Corp Frederick Inc, Ctr Canc Res Genet Core, Canc & Inflammat Program,Lab Expt Immunol, Frederick, MD 21702 USA. [Nelson, George] Frederick Natl Lab Canc Res, Sci Applicat Int Corp Frederick Inc, Ctr Canc Res Genet Core, Basic Res Program, Frederick, MD 21702 USA. [Kulkarni, Smita; Qi, Ying; Pereyra, Florencia; Ramsuran, Veron; Apps, Richard; Gao, Xiaojiang; Yuki, Yuko; Lied, Alexandra; Walker, Bruce D.; Carrington, Mary] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA 02139 USA. [McLaren, Paul; Fellay, Jacques] Univ Lausanne, Ecole Polytech Fed Lausanne, Sch Life Sci, CH-1011 Lausanne, Switzerland. [McLaren, Paul; Fellay, Jacques] Univ Lausanne, Inst Microbiol, CH-1011 Lausanne, Switzerland. [Chen, Haoyan; Liao, Wilson] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94115 USA. [Chen, Haoyan] Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Digest Dis, Dept Gastroenterol,Ren Ji Hosp, Shanghai 200001, Peoples R China. [Ganesan, Anuradha] Uniformed Serv Univ Hlth Sci, Infect Dis Clin Res Program, Bethesda, MD 20817 USA. [Hunt, Peter W.; Deeks, Steven G.] Univ Calif San Francisco, San Francisco Gen Hosp, AIDS Div, San Francisco, CA 94110 USA. [Wolinsky, Steven] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60611 USA. RP Carrington, M (reprint author), Frederick Natl Lab Canc Res, Sci Applicat Int Corp Frederick Inc, Ctr Canc Res Genet Core, Canc & Inflammat Program,Lab Expt Immunol, Frederick, MD 21702 USA. EM carringm@mail.nih.gov RI SHCS, int. coll. A/G-4083-2011; Fellay, Jacques/A-6681-2009; SHCS, all/G-4072-2011; OI Fellay, Jacques/0000-0002-8240-939X; Wolinsky, Steven/0000-0002-9625-6697 FU Swiss National Science Foundation [33CSC0-108787]; National Institute of Allergy and Infectious Diseases (NIAID); National Cancer Institute (NCI); National Heart, Lung and Blood Institute (NHLBI) [UO1-AI-35042, 5-MO1-RR-00722]; National Heart, Lung and Blood Institute (NHLBI) ([General Clinical Research Center]) [UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, UO1-AI-35041]; IHCS; Bill and Melinda Gates Foundation; AIDS Healthcare Foundation; Harvard University Center for AIDS Research; National Institutes of Health (NIH) [P30 AI060354]; NIH, NIAID; NIH, NCI; NIH, National Institute of Child Health and Human Development; NIH, NHLBI; NIH, National Institute on Drug Abuse; NIH, National Institute of Mental Health; NIH, National Institute on Aging; NIH, Fogarty International Center; NIH, Office of AIDS Research; NCI, NIH [HHSN261200800001E, N02-CP-55504, R01-DA04334, R01-DA12568]; Mark and Lisa Schwartz Foundation; Ragon Institute; NIH NIAID Center for HIV/AIDS Vaccine Immunology [U01-AI-067854]; [RO1 AI087145]; [K24AI069994]; [P30 AI027763]; [UL1 RR024131]; [P30 MH62246]; [R24 AI067039] FX We thank Drs. David Goldstein and Paul de Bakker for helpful discussions and review of the manuscript. We also thank the patients and investigators contributing to samples studied in the Study of the Consequences of the Protease Inhibitor Era (SCOPE), International HIV Controllers Study (IHCS), Swiss HIV Cohort Study (SHCS), and US Military HIV Natural History Study (NHS). SHCS (supported by Swiss National Science Foundation Grant 33CSC0-108787), SCOPE (supported by Grants RO1 AI087145, K24AI069994, P30 AI027763, UL1 RR024131, P30 MH62246, and R24 AI067039), and Multicenter AIDS Cohort Study (MACS) cohorts [funded by the National Institute of Allergy and Infectious Diseases (NIAID), with supplemental funding from the National Cancer Institute (NCI) and the National Heart, Lung and Blood Institute (NHLBI) (Grants UO1-AI-35042, 5-MO1-RR-00722 [General Clinical Research Center], UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613 and UO1-AI-35041)] and the Infectious disease clinical research program HIV Working group for the NHS samples. This publication resulted in part from research supported by the IHCS, funded by the Bill and Melinda Gates Foundation, the AIDS Healthcare Foundation, and the Harvard University Center for AIDS Research, a program funded by National Institutes of Health (NIH) Grant P30 AI060354, which is supported by the following NIH Co-Funding and Participating Institutes and centers: NIAID, NCI, National Institute of Child Health and Human Development, NHLBI, National Institute on Drug Abuse, National Institute of Mental Health, National Institute on Aging, Fogarty International Center, and Office of AIDS Research. This project has been funded in part with federal funds from the NCI, NIH, under Contracts HHSN261200800001E, N02-CP-55504, R01-DA04334, and R01-DA12568. This research was supported in part by a grant from the Bill and Melinda Gates Foundation as part of the Collaboration for AIDS Vaccine Discovery, the Mark and Lisa Schwartz Foundation, the Ragon Institute, and the NIH NIAID Center for HIV/AIDS Vaccine Immunology (Grant U01-AI-067854). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services or the Department of Defense, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 29 TC 27 Z9 27 U1 0 U2 8 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 17 PY 2013 VL 110 IS 51 BP 20705 EP 20710 DI 10.1073/pnas.1312237110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 273PR UT WOS:000328548600078 PM 24248364 ER PT J AU Peterson, VM Castro, CM Chung, J Miller, NC Ullal, AV Castano, MD Penson, RT Lee, H Birrer, MJ Weissleder, R AF Peterson, Vanessa M. Castro, Cesar M. Chung, Jaehoon Miller, Nathan C. Ullal, Adeeti V. Castano, Maria D. Penson, Richard T. Lee, Hakho Birrer, Michael J. Weissleder, Ralph TI Ascites analysis by a microfluidic chip allows tumor-cell profiling SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE biomarkers; molecular profiling; personalized medicine ID FOLLICLE-STIMULATING-HORMONE; EPITHELIAL OVARIAN CARCINOMAS; SEROUS PAPILLARY CARCINOMA; PERITONEAL MESOTHELIOMAS; PROGNOSTIC-SIGNIFICANCE; ADHESION-MOLECULE; GROWTH PROMOTION; GENE-EXPRESSION; CANCER; RECEPTOR AB Ascites tumor cells (ATCs) represent a potentially valuable source of cells for monitoring treatment of ovarian cancer as it would obviate the need for more invasive surgical biopsies. The ability to perform longitudinal testing of ascites in a point-of-care setting could significantly impact clinical trials, drug development, and clinical care. Here, we developed a microfluidic chip platform to enrich ATCs from highly heterogeneous peritoneal fluid and then perform molecular analyses on these cells. We evaluated 85 putative ovarian cancer protein markers and found that nearly two-thirds were either nonspecific for malignant disease or had low abundance. Using four of the most promising markers, we prospectively studied 47 patients (33 ovarian cancer and 14 control). We show that a marker set (ATC(dx)) can sensitively and specifically map ATC numbers and, through its reliable enrichment, facilitate additional treatment-response measurements related to proliferation, protein translation, or pathway inhibition. C1 [Peterson, Vanessa M.; Castro, Cesar M.; Chung, Jaehoon; Miller, Nathan C.; Ullal, Adeeti V.; Castano, Maria D.; Lee, Hakho; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Castro, Cesar M.; Penson, Richard T.; Birrer, Michael J.; Weissleder, Ralph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Peterson, Vanessa M.; Miller, Nathan C.; Ullal, Adeeti V.] MIT, Cambridge, MA 02139 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu FU DOD [W81XWH-11-1-0706]; Merck Educational Assistance Fellowship; [P50CA086355]; [R01EB004626]; [R01EB010011]; [P01-CA139980]; [U54-CA151884]; [K12CA087723-11A1] FX We thank M. Pectasides and S. McDermott for sample collection; C. Krasner, L. Sullivan, and S. McIlvenna for patient referral; V. Vathipadiekal and P. Waterman for help growing cell lines; H. Saya (IAMR, Keio University) for CD44v9 antibody, L. Lizotte (REMS media services) for microchip pictures, A. Zaltsman for imaging, and Y. Fisher-Jeffes for review of the manuscript. This work was funded in part by Grants P50CA086355, R01EB004626, R01EB010011, P01-CA139980, U54-CA151884, K12CA087723-11A1, and DOD W81XWH-11-1-0706. V. M. P. was supported in part by a Merck Educational Assistance Fellowship. NR 62 TC 7 Z9 7 U1 2 U2 26 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 17 PY 2013 VL 110 IS 51 BP E4978 EP E4986 DI 10.1073/pnas.1315370110 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 273PR UT WOS:000328548600009 PM 24297935 ER PT J AU Chow, MJ Choi, M Yun, SH Zhang, YH AF Chow, Ming-Jay Choi, Myunghwan Yun, Seok Hyun Zhang, Yanhang TI The Effect of Static Stretch on Elastin Degradation in Arteries SO PLOS ONE LA English DT Article ID VASCULAR EXTRACELLULAR-MATRIX; BINDING-SITE AVAILABILITY; MECHANICAL-PROPERTIES; COLLAGEN; PROTEOGLYCANS; TISSUE; DIGESTION; ANEURYSMS; STRESS; MODEL AB Previously we have shown that gradual changes in the structure of elastin during an elastase treatment can lead to important transition stages in the mechanical behavior of arteries [1]. However, in vivo arteries are constantly being loaded due to systolic and diastolic pressures and so understanding the effects of loading on the enzymatic degradation of elastin in arteries is important. With biaxial tensile testing, we measured the mechanical behavior of porcine thoracic aortas digested with a mild solution of purified elastase (5 U/mL) in the presence of a static stretch. Arterial mechanical properties and biochemical composition were analyzed to assess the effects of mechanical stretch on elastin degradation. As elastin is being removed, the dimensions of the artery increase by more than 20% in both the longitude and circumference directions. Elastin assays indicate a faster rate of degradation when stretch was present during the digestion. A simple exponential decay fitting confirms the time constant for digestion with stretch (0.11 +/- 0.04 h(-1)) is almost twice that of digestion without stretch (0.069 +/- 0.028 h(-1)). The transition from J-shaped to S-shaped stress vs. strain behavior in the longitudinal direction generally occurs when elastin content is reduced by about 60%. Multiphoton image analysis confirms the removal/fragmentation of elastin and also shows that the collagen fibers are closely intertwined with the elastin lamellae in the medial layer. After removal of elastin, the collagen fibers are no longer constrained and become disordered. Release of amorphous elastin during the fragmentation of the lamellae layers is observed and provides insights into the process of elastin degradation. Overall this study reveals several interesting microstructural changes in the extracellular matrix that could explain the resulting mechanical behavior of arteries with elastin degradation. C1 [Chow, Ming-Jay; Zhang, Yanhang] Boston Univ, Dept Mech Engn, Boston, MA 02215 USA. [Zhang, Yanhang] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Choi, Myunghwan; Yun, Seok Hyun] Harvard Univ, Wellman Ctr Photomed, Cambridge, MA 02138 USA. [Choi, Myunghwan; Yun, Seok Hyun] Massachusetts Gen Hosp, Cambridge, MA USA. [Choi, Myunghwan] Korea Adv Inst Sci & Technol, Grad Sch Nanosci & Technol WCU, Taejon 305701, South Korea. RP Zhang, YH (reprint author), Boston Univ, Dept Mech Engn, Boston, MA 02215 USA. EM yanhang@bu.edu OI Choi, Myunghwan/0000-0002-4235-7003 FU NIH [HL098028] FX This work was supported by a grant from the NIH (HL098028) that was provided to Dr. Zhang. The imaging work was made possible through access to Dr. Yun's lab at Wellman Center for Photomedicine, P41EB015903. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 43 TC 3 Z9 3 U1 1 U2 11 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 16 PY 2013 VL 8 IS 12 AR e81951 DI 10.1371/journal.pone.0081951 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 276GD UT WOS:000328735700029 PM 24358135 ER PT J AU Dasgupta, SK Le, A Haudek, SB Entman, ML Rumbaut, RE Thiagarajan, P AF Dasgupta, Swapan K. Anhquyen Le Haudek, Sandra B. Entman, Mark L. Rumbaut, Rolando E. Thiagarajan, Perumal TI Rho Associated Coiled-Coil Kinase-1 Regulates Collagen-Induced Phosphatidylserine Exposure in Platelets SO PLOS ONE LA English DT Article ID BCL-X(L)-INHIBITORY BH3 MIMETICS; ACTIN STRESS FIBERS; PROTEIN-KINASE; SHAPE CHANGE; PROCOAGULANT RESPONSE; SIGNALING PATHWAYS; THROMBUS FORMATION; ROCK-II; PHOSPHORYLATION; CYTOSKELETON AB Background: The transbilayer movement of phosphatidylserine mediates the platelet procoagulant activity during collagen stimulation. The Rho-associated coiled-coil kinase (ROCK) inhibitor Y-27632 inhibits senescence induced but not activation induced phosphatidylserine exposure. To investigate further the specific mechanisms, we now utilized mice with genetic deletion of the ROCK1 isoform. Methods and Results: ROCK1-deficient mouse platelets expose significantly more phosphatidylserine and generate more thrombin upon activation with collagen compared to wild-type platelets. There were no significant defects in platelet shape change, aggregation, or calcium response compared to wild-type platelets. Collagen-stimulated ROCK1-deficient platelets also displayed decreased phosphorylation levels of Lim Kinase-1 and cofilin-1. However, there was no reduction in phosphorylation levels of myosin phosphatase subunit-1 (MYPT1) or myosin light chain (MLC). In an in vivo light/dye-induced endothelial injury/thrombosis model, ROCK1-deficient mice presented a shorter occlusion time in cremasteric venules when compared to wild-type littermates (3.16 +/- 1.33 min versus 6.6 +/- 2.6 min; p = 0.01). Conclusions: These studies define ROCK1 as a new regulator for collagen-induced phosphatidylserine exposure in platelets with functional consequences on thrombosis. This effect was downstream of calcium signaling and was mediated by Lim Kinase-1 / cofilin-1-induced cytoskeletal changes. C1 [Dasgupta, Swapan K.; Anhquyen Le; Rumbaut, Rolando E.; Thiagarajan, Perumal] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Ctr Translat Res Inflammatory Dis, Houston, TX 77030 USA. [Dasgupta, Swapan K.; Anhquyen Le; Thiagarajan, Perumal] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. [Haudek, Sandra B.; Entman, Mark L.; Rumbaut, Rolando E.; Thiagarajan, Perumal] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Rumbaut, Rolando E.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. RP Dasgupta, SK (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Ctr Translat Res Inflammatory Dis, Houston, TX 77030 USA. EM swapand@bcm.edu OI Thiagarajan, Perumal/0000-0003-2186-7036 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development; National Institutes of Health [HL116524, HL089792]; National Blood Foundation FX This study was supported by grants from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development (to PT and RR), grants from National Institutes of Health (HL116524 to RR and PT; HL089792 to MLE and SBH) and by a grant from the National Blood Foundation (to SKD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 2 Z9 2 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 16 PY 2013 VL 8 IS 12 AR e84649 DI 10.1371/journal.pone.0084649 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 276GD UT WOS:000328735700164 PM 24358370 ER PT J AU Tecilazich, F Dinh, T Pradhan-Nabzdyk, L Leal, E Tellechea, A Kafanas, A Gnardellis, C Magargee, ML Dejam, A Toxavidis, V Tigges, JC Carvalho, E Lyons, TE Veves, A AF Tecilazich, Francesco Thanh Dinh Pradhan-Nabzdyk, Leena Leal, Ermelindo Tellechea, Ana Kafanas, Antonios Gnardellis, Charalambos Magargee, Mary L. Dejam, Andre Toxavidis, Vasilis Tigges, John C. Carvalho, Eugenia Lyons, Thomas E. Veves, Aristidis TI Role of Endothelial Progenitor Cells and Inflammatory Cytokines in Healing of Diabetic Foot Ulcers SO PLOS ONE LA English DT Article ID BONE-MARROW; MOBILIZATION; ULCERATION; ISCHEMIA; OUTCOMES; EXPRESSION; MELLITUS; NUMBERS; MARKERS; BLOOD AB Background: To evaluate changes in endothelial progenitor cells (EPCs) and cytokines in patients with diabetic foot ulceration (DFU) in association with wound healing. Methods: We studied healthy subjects, diabetic patients not at risk of DFU, at risk of DFU and with active DFU. We prospectively followed the DFU patients over a 12-week period. We also investigated similar changes in diabetic rabbit and mouse models of wound healing. Results: All EPC phenotypes except the kinase insert domain receptor (KDR)(+)CD133(+) were reduced in the at risk and the DFU groups compared to the controls. There were no major EPC differences between the control and not at risk group, and between the at risk and DFU groups. Serum stromal-cell derived factor-1 (SDF-1) and stem cell factor (SCF) were increased in DFU patients. DFU patients who healed their ulcers had lower CD34(+)KDR(+) count at visits 3 and 4, serum c-reactive protein (CRP) and granulocyte-macrophage colony-stimulating factor (GM-CSF) at visit 1, interleukin-1 (IL-1) at visits 1 and 4. EPCs tended to be higher in both diabetic animal models when compared to their non-diabetic counterparts both before and ten days after wounding. Conclusions: Uncomplicated diabetes does not affect EPCs. EPCs are reduced in patients at risk or with DFU while complete wound healing is associated with CD34(+)KDR(+) reduction, suggesting possible increased homing. Low baseline CRP, IL-1 alpha and GM-CSF serum levels were associated with complete wound healing and may potentially serve as prognostic markers of DFU healing. No animal model alone is representative of the human condition, indicating the need for multiple experimental models. C1 [Tecilazich, Francesco; Thanh Dinh; Pradhan-Nabzdyk, Leena; Leal, Ermelindo; Tellechea, Ana; Kafanas, Antonios; Magargee, Mary L.; Carvalho, Eugenia; Lyons, Thomas E.; Veves, Aristidis] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Microcirculat Lab, Boston, MA 02215 USA. [Tecilazich, Francesco; Thanh Dinh; Pradhan-Nabzdyk, Leena; Leal, Ermelindo; Tellechea, Ana; Kafanas, Antonios; Magargee, Mary L.; Carvalho, Eugenia; Lyons, Thomas E.; Veves, Aristidis] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Joslin Beth Israel Deaconess Foot Ctr, Boston, MA 02215 USA. [Tellechea, Ana] Univ Coimbra, Ctr Neurosci & Cell Biol, Coimbra, Portugal. [Gnardellis, Charalambos] Technol Educ Inst Messolonghi, Mesolongion, Greece. [Dejam, Andre] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Cardiol, Boston, MA 02215 USA. [Toxavidis, Vasilis; Tigges, John C.] Beth Israel Deaconess Med Ctr, Flow Cytometry Core Facil, Boston, MA 02215 USA. [Toxavidis, Vasilis; Tigges, John C.] Harvard Stem Cell Inst, Boston, MA USA. RP Veves, A (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Microcirculat Lab, Boston, MA 02215 USA. EM aveves@bidmc.harvard.edu OI Carvalho, Eugenia/0000-0001-6264-3632; Tellechea, Ana/0000-0001-9387-7706 FU National Institutes of Health [R01-DK076937, R21-DK082987, R01 NS066205]; FCT [SFRH/BPD/46341/2008, SFRH/BD/48624/2008] FX This work was supported by National Institutes of Health Grants R01-DK076937, R21-DK082987 and R01 NS066205 to AV, as well as FCT fellowships SFRH/BPD/46341/2008 (EL) and SFRH/BD/48624/2008 (AT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 13 Z9 14 U1 1 U2 11 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 16 PY 2013 VL 8 IS 12 AR UNSP e83314 DI 10.1371/journal.pone.0083314 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 276GD UT WOS:000328735700118 PM 24358275 ER PT J AU Fard, AM Vacas-Jacques, P Hamidi, E Wang, H Carruth, RW Gardecki, JA Tearney, GJ AF Fard, Ali M. Vacas-Jacques, Paulino Hamidi, Ehsan Wang, Hao Carruth, Robert W. Gardecki, Joseph A. Tearney, Guillermo J. TI Optical coherence tomography - near infrared spectroscopy system and catheter for intravascular imaging SO OPTICS EXPRESS LA English DT Article ID IN-VIVO; FLUORESCENCE SPECTROSCOPY; PHOTON MIGRATION; PLAQUE; MICROSCOPY; DEPTH; FIBER; PERFORMANCE; ENDOSCOPY; LASER AB Owing to its superior resolution, intravascular optical coherence tomography (IVOCT) is a promising tool for imaging the microstructure of coronary artery walls. However, IVOCT does not identify chemicals and molecules in the tissue, which is required for a more complete understanding and accurate diagnosis of coronary disease. Here we present a dual-modality imaging system and catheter that uniquely combines IVOCT with diffuse near-infrared spectroscopy (NIRS) in a single dual-modality imaging device for simultaneous acquisition of microstructural and compositional information. As a proof-of-concept demonstration, the device has been used to visualize co-incident microstructural and spectroscopic information obtained from a diseased cadaver human coronary artery. (C) 2013 Optical Society of America C1 [Fard, Ali M.; Vacas-Jacques, Paulino; Hamidi, Ehsan; Wang, Hao; Carruth, Robert W.; Gardecki, Joseph A.; Tearney, Guillermo J.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Fard, Ali M.; Vacas-Jacques, Paulino; Hamidi, Ehsan; Wang, Hao; Carruth, Robert W.; Gardecki, Joseph A.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wang, Hao] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Tearney, Guillermo J.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Tearney, Guillermo J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Tearney, GJ (reprint author), Harvard Univ, Sch Med, Wellman Ctr Photomed, 55 Fruit St, Boston, MA 02114 USA. EM gtearney@partners.org FU National Institute of Health [R01HL76398, R01HL093717] FX This work was financially supported by National Institute of Health under grant number R01HL76398 and R01HL093717. Massachusetts General Hospital has a licensing arrangement with Terumo Corporation regarding OFDI technology. Dr. Tearney has the rights to receive royalties as a result of this licensing arrangement. NR 41 TC 14 Z9 16 U1 1 U2 11 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD DEC 16 PY 2013 VL 21 IS 25 BP 30849 EP 30858 DI 10.1364/OE.21.030849 PG 10 WC Optics SC Optics GA 273ZV UT WOS:000328575700067 PM 24514658 ER PT J AU Hajrasouliha, AR Sadrai, Z Lee, HK Chauhan, SK Dana, R AF Hajrasouliha, Amir R. Sadrai, Zahra Lee, Hyung K. Chauhan, Sunil K. Dana, Reza TI Expression of the chemokine decoy receptor D6 mediates dendritic cell function and promotes corneal allograft rejection SO MOLECULAR VISION LA English DT Article ID INFLAMMATORY CC CHEMOKINES; CUTTING EDGE; COLON-CANCER; TRANSPLANTATION; MICE; RESPONSES AB Purpose: To identify the role of chemokine receptor 6 (D6) expression by dendritic cells (DCs) and its role in corneal transplant immunity. Methods: Flow cytometry analysis was used to assess the expression level of the D6 chemokine receptor in different leukocyte populations and DC maturation following lipopolysaccharides (LPS) stimulation of bone marrow-derived DCs isolated from wild-type (WT) or D6(-/-) mice (C57BL/6 background). Mixed-lymphocyte reactions and delayed-type hypersensitivity assays were performed with bone marrow-derived DCs from WT or D6(-/-) mice to evaluate T-cell alloreactivity. Adoptive transfer experiments with T cells from WT or D6(-/-) hosts with BALB/c corneal allografts were performed. Graft opacity was assessed over an 8-week period, and graft survival was plotted using Kaplan-Meier survival curves. Results: Expression of the D6 chemokine receptor was significantly higher in DCs compared to other leukocyte subpopulations, including neutrophils, lymphocytes, and monocytes/macrophages. LPS challenge of D6(-/-) bone marrow-derived DCs elicited significantly lower levels of major histocompatibility complex II and costimulatory molecules (CD40, CD80, and CD86) compared to WT bone marrow-derived DCs, indicating the role of the D6 chemokine receptor in DC maturation. Further, DCs isolated from D6(-/-) mice induced less T-cell proliferation (p=0.001) and interferon-gamma production in T cells of draining lymph nodes compared to WT mice following corneal transplantation (p=0.001). Moreover, adoptively transferred T cells from D6(-/-) corneal transplanted mice to WT mice led to impaired graft rejection, compared to the hosts that received T cells from the WT transplanted mice. Conclusions: We demonstrated D6 chemokine receptor expression by DCs and identified its critical function in multiple aspects of DC biology, including maturation and consequent elicitation of alloreactive T-cell responses that are responsible for corneal allograft rejection. C1 [Hajrasouliha, Amir R.; Sadrai, Zahra; Lee, Hyung K.; Chauhan, Sunil K.; Dana, Reza] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. RP Dana, R (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM reza_dana@meei.harvard.edu FU NIH [RO1EY12963]; Eye Bank Association of America FX We thank Dr. Donald N. Cook from National Institute of Environmental Science for providing us with D6-deficient mice and Dr. Daniel Saban of Duke University for helpful scientific discussions. This work was supported by the NIH RO1EY12963 and the Eye Bank Association of America. NR 24 TC 5 Z9 6 U1 0 U2 1 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD DEC 16 PY 2013 VL 19 BP 2517 EP 2525 PG 9 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 272RI UT WOS:000328477500001 PM 24357920 ER PT J AU Wilson, IB Bangsberg, DR Shen, J Simoni, JM Reynolds, NR Goggin, K Gross, R Arnsten, JH Remien, RH Erlen, JA Liu, HH AF Wilson, Ira B. Bangsberg, David R. Shen, Jie Simoni, Jane M. Reynolds, Nancy R. Goggin, Kathy Gross, Robert Arnsten, Julia H. Remien, Robert H. Erlen, Judith A. Liu, Honghu CA Multisite Adherence Collaboration TI Heterogeneity Among Studies in Rates of Decline of Antiretroviral Therapy Adherence Over Time: Results From the Multisite Adherence Collaboration on HIV 14 Study SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; antiretroviral therapy; medication adherence; longitudinal studies; pooled analysis ID ART ADHERENCE; RISK-FACTORS; COHORT; POPULATION; PATTERNS; PREDICTORS; OUTCOMES; HAART; RACE/ETHNICITY; NONADHERENCE AB Objective: To use electronic drug monitoring to determine if adherence to HIV antiretroviral therapy (ART) changes over time, whether changes are linear, and how the declines vary by study. Design: We conducted a longitudinal study of pooled data from 11 different studies of HIV-infected adults using ART. The main outcome was ART adherence (percent of prescribed doses taken) measured by electronic drug monitoring. We modeled and compared changes in adherence over time using repeated measures linear mixed effects models and generalized additive mixed models (GAMMs). Indicator variables were used to examine the impact of individual studies, and the variation across studies was evaluated using study-specific parameter estimates calculated by using interaction terms of study and time. Results: The mean age of the subjects was 41 years, 35% were female, most had high school education or less, and 46% were African American. In GAMMs, adherence declined over time. The GAMMs further suggested that the decline was nonlinear, and in both sets of models, there was considerable study-to-study variability in how adherence changed over time. Limitations: Findings may not be generalizable to non-US populations or to patients not in clinical studies. Conclusions: Although overall ART adherence declined with time, not all studies showed declines, and a number of patterns of change were seen. Studies that identify clinical and organizational factors associated with these different patterns are needed. Models of changes in adherence with time should take account of possible nonlinear effects. C1 [Wilson, Ira B.; Liu, Honghu] Brown Univ, Sch Publ Hlth, Dept Hlth Serv Policy & Practice, Providence, RI 02912 USA. [Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Bangsberg, David R.] Ragon Inst MGH MIT & Harvard, Boston, MA USA. [Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. [Shen, Jie] Univ Calif Los Angeles, Sch Dent, Div Publ Hlth & Community Dent, Los Angeles, CA 90024 USA. [Simoni, Jane M.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. [Reynolds, Nancy R.] Yale Univ, Sch Nursing, New Haven, CT 06536 USA. [Goggin, Kathy] Univ Missouri, Childrens Mercy Hosp, Div Hlth Serv & Outcomes Res, Kansas City, MO 64108 USA. [Gross, Robert] Univ Penn, Ctr Clin Epidemiol & Biostat, Dept Med Infect Dis, Perelman Sch Med, Philadelphia, PA 19104 USA. [Arnsten, Julia H.] Montifiore Hosp, Albert Einstein Coll Med, Dept Med, Bronx, NY USA. [Remien, Robert H.] Columbia Univ, Dept Psychiat, New York, NY USA. [Erlen, Judith A.] Univ Pittsburgh, Sch Nursing, Dept Hlth & Community Syst, Pittsburgh, PA 15261 USA. RP Wilson, IB (reprint author), Brown Univ, Sch Publ Hlth, Dept Hlth Serv Policy & Practice, G-121-7,121 South Main St, Providence, RI 02912 USA. EM ira_wilson@brown.edu RI Wilson, Ira/F-9190-2016 OI Wilson, Ira/0000-0002-0246-738X FU Multisite Adherence Collaboration in HIV (MACH14) from the National Institute of Mental Health, Office on AIDS [R01MH078773]; National Institute of Mental Health [P01 MH49548, MH58986, RO1MH61695, CC99-SD-003, CC02-SD-003, R01DA015679]; [R01DA11869]; [MH54907]; [2R01NR04749]; [R01NR04749]; [R01MH068197]; [R01 DA13826]; [K23MH01862]; [MH01584]; [R01 AI41413]; [R01 MH61173]; [NIH/NIAID AI38858]; [AI069419]; [K02 DA017277]; [R01DA15215] FX Supported by the Multisite Adherence Collaboration in HIV (MACH14) grant R01MH078773 from the National Institute of Mental Health, Office on AIDS. The original grants of individual participating studies are R01DA11869, MH54907, 2R01NR04749, R01NR04749, R01MH068197, R01 DA13826, K23MH01862, MH01584, R01 AI41413, R01 MH61173, NIH/NIAID AI38858, AI069419, K02 DA017277, R01DA15215, National Institute of Mental Health P01 MH49548, MH58986, RO1MH61695, CC99-SD-003, CC02-SD-003, and R01DA015679. The content of the paper is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 35 TC 15 Z9 15 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD DEC 15 PY 2013 VL 64 IS 5 BP 448 EP 454 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 300HX UT WOS:000330456100004 PM 24225904 ER PT J AU Cetrulo, CL Torabi, R Scalea, JR Shimizu, A Barone, AAL Gillon, BC Tasaki, M Leonard, DA Cormack, TA Villani, V Randolph, MA Sachs, DH Yamada, K AF Cetrulo, Curtis L., Jr. Torabi, Radbeh Scalea, Joseph R. Shimizu, Akira Barone, Angelo A. Leto Gillon, Bradford C. Tasaki, Masayuki Leonard, David A. Cormack, Taylor A. Villani, Vincenzo Randolph, Mark A. Sachs, David H. Yamada, Kazuhiko TI Vascularized Composite Allograft Transplant Survival in Miniature Swine: Is MHC Tolerance Sufficient for Acceptance of Epidermis? SO TRANSPLANTATION LA English DT Article DE Massachusetts General Hospital miniature swine; Vascularized composite allograft; Skin-specific antigens; Vascularized skin ID MAJOR HISTOCOMPATIBILITY COMPLEX; MISMATCHED RENAL-ALLOGRAFTS; COST-EFFECTIVENESS; LUNG TRANSPLANTATION; INDUCTION; THYMUS; MODEL; COTRANSPLANTATION; VASCULOPATHY; RECIPIENTS AB Background. We have previously reported that Massachusetts General Hospital miniature swine, which had accepted class I-mismatched kidneys long-term after 12 days of high-dose cyclosporine A, uniformly accepted donor-major histocompatibility complex (MHC)-matched kidneys without immunosuppression but rejected donor MHC matched split-thickness skin grafts by day 25, without changes in renal graft function or antidonor in vitro responses. We have now tested whether this "split tolerance" would also be observed for the primarily vascularized skin of vascularized composite allografts (VCAs). Methods. Group 1 animals (n=3) received donor MHC-matched VCAs less than 70 days after primary kidney transplant (KTx). Group 2 animals (n=3) received a second donor-matched kidney transplant followed by a donor-matched VCA more than 200 days after primary KTx. Results. Animals in Group 1 lost the epidermis on days 28, 30, and 40, with all other components of the VCAs remaining viable. Histology showed cellular infiltration localized to dermal-epidermal junction. One of three recipients of VCAs in Group 2, accepted all components of the VCA, including epidermis (9200 days). The other two recipients lost only the epidermis on days 45 and 85, with survival of the remainder of the VCA long-term. Conclusions. All tissues of a VCA are accepted long-term on animals tolerant of class I-mismatched kidneys, with the exception of epidermis, the survival of which is markedly prolonged compared with split-thickness skin grafts but not indefinite. Exposure of tolerant animals to second donor-matched kidneys before VCA increases the longevity of the VCA epidermis, suggesting an increase in the immunomodulatory mechanisms associated with tolerance of the kidney. C1 [Cetrulo, Curtis L., Jr.; Torabi, Radbeh; Scalea, Joseph R.; Shimizu, Akira; Barone, Angelo A. Leto; Gillon, Bradford C.; Tasaki, Masayuki; Leonard, David A.; Cormack, Taylor A.; Villani, Vincenzo; Randolph, Mark A.; Sachs, David H.; Yamada, Kazuhiko] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. [Cetrulo, Curtis L., Jr.; Torabi, Radbeh; Barone, Angelo A. Leto; Leonard, David A.; Randolph, Mark A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg, Boston, MA 02129 USA. RP Yamada, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH East,Bldg 149-9014,13th St, Boston, MA 02129 USA. EM kaz.yamada@tbrc.mgh.harvard.edu OI Villani, Vincenzo/0000-0002-6078-9766 FU Massachusetts General Hospital Swine Facility grant [C06 RR020135-01] FX This research was partially supported by the Massachusetts General Hospital Swine Facility grant C06 RR020135-01. NR 31 TC 3 Z9 3 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD DEC 15 PY 2013 VL 96 IS 11 BP 966 EP 974 DI 10.1097/TP.0b013e3182a579d0 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 299ZY UT WOS:000330435400011 PM 24056624 ER PT J AU Limaye, SA Haddad, RI Cilli, F Sonis, ST Colevas, AD Brennan, MT Hu, KS Murphy, BA AF Limaye, Sewanti Atul Haddad, Robert I. Cilli, Fiona Sonis, Stephen T. Colevas, A. Dimitrios Brennan, Michael T. Hu, Kenneth S. Murphy, Barbara A. TI Phase 1b, Multicenter, Single Blinded, Placebo-Controlled, Sequential Dose Escalation Study to Assess the Safety and Tolerability of Topically Applied AG013 in Subjects With Locally Advanced Head and Neck Cancer Receiving Induction Chemotherapy SO CANCER LA English DT Article DE head and neck cancer; induction chemotherapy; oral mucositis; mouth rinse; safety and tolerability ID FLUOROURACIL-BASED CHEMOTHERAPY; MODIFIED LACTOCOCCUS-LACTIS; INTESTINAL TREFOIL FACTOR; COLORECTAL-CANCER; ORAL MUCOSITIS; INTERLEUKIN-10; RADIOTHERAPY; PREVENTION; CISPLATIN; DOCETAXEL AB BACKGROUND: Oral mucositis (OM) is a significant toxicity of induction chemotherapy for locally advanced head and neck cancer (LAHNC). The safety and tolerability of AG013, an oral rinse containing recombinant Lactococcus lactis secreting mucosal protectant human trefoil factor 1 (hTFF1), was evaluated in a phase 1b study in LAHNC subjects who received induction with cisplatin, 5-fluorouracil, with or without docetaxel. Preliminary efficacy data were also obtained. METHODSA total of 25 of 52 LAHNC subjects who were followed during induction cycle 1 developed ulcerative oral mucositis (UOM; World Health Organization grade>2) and were randomized to AG013:placebo (5:2 ratio) for cycle 2. Dosing schedules of 1, 3, or 6 times daily were evaluated (2 x 10(11), 6 x 10(11), and 1.2 x 10(12) colony forming units per day, respectively). OM was evaluated daily from cycle 2, day 1 through 14, using World Health Organization criteria. Pharmacokinetic assessment was also conducted. RESULTSAG013 bacteria were not detected in blood. Oral live AG013 bacterial and hTFF1 levels in saliva and oral mucosa were equivalent among treatment groups. The most frequently occurring adverse events were nausea, oral pain, fatigue, diarrhea, and mucosal inflammation. Only 12% (3 of 25 adverse events), mainly nausea, were attributed to the investigational medicinal product: AG013 or placebo. Efficacy analysis showed a 35% reduction in percentage of days with UOM in AG013-subjects versus placebo. All placebo subjects experienced2 days of UOM, whereas 29% of AG013 subjects had UOM for 0 or 1 day. AG013 use resulted in fewer unscheduled office and emergency room visits. No differences were noted in mouth and throat soreness, opioid use, or gastrostomy tube placement. CONCLUSIONSAG013 was safe and well tolerated. Preliminary efficacy data support further study. Cancer 2013;119:4268-4276. (c) 2013 American Cancer Society. C1 [Limaye, Sewanti Atul; Haddad, Robert I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Cilli, Fiona] ActoGeniX NV, Zwijnaarde, Belgium. [Sonis, Stephen T.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Sonis, Stephen T.] Biomodels LLC, Watertown, MA USA. [Colevas, A. Dimitrios] Stanford Univ, Stanford, CA 94305 USA. [Brennan, Michael T.] Carolinas Med Ctr, Charlotte, NC 28203 USA. [Hu, Kenneth S.] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA. [Murphy, Barbara A.] Vanderbilt Univ, Ctr Med, Nashville, TN 37232 USA. RP Limaye, SA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM sewantia_limaye@dfci.harvard.edu FU ActoGeniX NV FX Research support has been provided by ActoGeniX NV. NR 18 TC 19 Z9 19 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD DEC 15 PY 2013 VL 119 IS 24 BP 4268 EP 4276 DI 10.1002/cncr.28365 PG 9 WC Oncology SC Oncology GA 295BP UT WOS:000330091900010 PM 24114811 ER PT J AU Fuchs, CS Fakih, M Schwartzberg, L Cohn, AL Yee, L Dreisbach, L Kozloff, MF Hei, YJ Galimi, F Pan, Y Haddad, V Hsu, CP Sabin, A Saltz, L AF Fuchs, Charles S. Fakih, Marwan Schwartzberg, Lee Cohn, Allen L. Yee, Lorrin Dreisbach, Luke Kozloff, Mark F. Hei, Yong-jiang Galimi, Francesco Pan, Yang Haddad, Vincent Hsu, Cheng-Pang Sabin, Antony Saltz, Leonard TI TRAIL Receptor Agonist Conatumumab With Modified FOLFOX6 Plus Bevacizumab for First-Line Treatment of Metastatic Colorectal Cancer SO CANCER LA English DT Article DE AMG 655; bevacizumab; death receptor 5 agonist; FOLFOX; conatumumab; metastatic colorectal cancer ID CELL LUNG-CANCER; ADVANCED SOLID MALIGNANCIES; MONOCLONAL-ANTIBODY; PHASE-I; MAPATUMUMAB; TUMORS; CARBOPLATIN; COMBINATION; PACLITAXEL; APOPTOSIS AB BACKGROUND: In patients with previously untreated metastatic colorectal cancer (mCRC), we conducted a phase 1b/randomized phase 2 trial to define the safety, tolerability, and efficacy of mFOLFOX6 plus bevacizumab (mFOLFOX6/bev) with conatumumab, an investigational, fully human monoclonal IgG1 antibody that specifically activates death receptor 5 (DR5). METHODSTwelve patients were enrolled in a phase 1b open-label dose-escalation trial of conatumumab with mFOLFOX6/bev; thereafter, 190 patients were randomized 1:1:1 to receive mFOLFOX6/bev in combination with 2 mg/kg conatumumab, 10 mg/kg conatumumab, or placebo. Therapy cycles were repeated every 2 weeks until disease progression or the occurrence of unacceptable toxicity. RESULTSIn phase 1b, conatumumab with mFOLFOX6/bev was tolerated without apparent added toxicity over mFOLFOX6/bev alone. In phase 2, conatumumab with mFOLFOX6/bev did not confer a benefit in progression-free survival when compared with placebo with mFOLFOX6/bev. Toxicity was similar in all treatment arms. Following treatment, similar increases in circulating caspase-3 levels were observed in all arms. CONCLUSIONSConatumumab with mFOLFOX6/bev did not offer improved efficacy over the same chemotherapy with placebo in first-line treatment of patients with mCRC. These data do not support further development of conatumumab in advanced CRC. Cancer 2013;119:4290-4298. (c) 2013 American Cancer Society. C1 [Fuchs, Charles S.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Fakih, Marwan] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Schwartzberg, Lee] West Clin, Memphis, TN USA. [Cohn, Allen L.] Rocky Mt Canc Ctr, Denver, CO USA. [Yee, Lorrin] PLLC, NW Med Specialties, Tacoma, WA USA. [Dreisbach, Luke] Desert Hematol Oncol Med Grp Inc, Rancho Mirage, CA USA. [Kozloff, Mark F.] Univ Chicago, Chicago, IL 60637 USA. [Hei, Yong-jiang; Hsu, Cheng-Pang] Amgen Inc, Thousand Oaks, CA 91320 USA. [Galimi, Francesco] Amgen Inc, San Francisco, CA USA. [Pan, Yang] Amgen Inc, Seattle, WA USA. [Haddad, Vincent; Sabin, Antony] Amgen Ltd, Cambridge, England. [Saltz, Leonard] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Fuchs, CS (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM cfuchs@partners.org FU Amgen Inc FX This study was funded by Amgen Inc (Clinicaltrials.gov number NCT00625651). NR 29 TC 22 Z9 23 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD DEC 15 PY 2013 VL 119 IS 24 BP 4290 EP 4298 DI 10.1002/cncr.28353 PG 9 WC Oncology SC Oncology GA 295BP UT WOS:000330091900013 PM 24122767 ER PT J AU Vega, RBM Kim, J Bussiere, M Hattangadi, J Hollander, A Michalski, J Tarbell, NJ Yock, T MacDonald, SM AF Vega, Raymond B. Mailhot Kim, Jane Bussiere, Marc Hattangadi, Jona Hollander, Abby Michalski, Jeff Tarbell, Nancy J. Yock, Torunn MacDonald, Shannon M. TI Cost Effectiveness of Proton Therapy Compared With Photon Therapy in the Management of Pediatric Medulloblastoma SO CANCER LA English DT Article DE medulloblastoma; cost effectiveness; comparative effectiveness; proton; Monte Carlo ID RADIATION-THERAPY; CHILDHOOD MEDULLOBLASTOMA; FOCUSED UPDATE; POTENTIAL ROLE; UNITED-STATES; BEAM THERAPY; BRAIN-TUMORS; CANCER; RADIOTHERAPY; HEALTH AB BACKGROUND: Proton therapy has been a hotly contested issue in both scientific publications and lay media. Proponents cite the modality's ability to spare healthy tissue, but critics claim the benefit gained from its use does not validate its cost compared with photon therapy. The objective of this study was to evaluate the cost effectiveness of proton therapy versus photon therapy in the management of pediatric medulloblastoma. METHODSA cost-effective analysis was performed from the societal perspective using a Monte Carlo simulation model. A population of pediatric medulloblastoma survivors aged 18 years was studied who had received treatment at age 5 years and who were at risk of developing 10 adverse events, such as growth hormone deficiency, coronary artery disease, ototoxicity, secondary malignant neoplasm, and death. Costing data included the cost of investment and the costs of diagnosis and management of adverse health states from institutional and Medicare data. Longitudinal outcomes data and recent modeling studies informed risk parameters for the model. Incremental cost-effectiveness ratios were used to measure outcomes. RESULTSResults from the base case demonstrated that proton therapy was associated with higher quality-adjusted life years and lower costs; therefore, it dominated photon therapy. In 1-way sensitivity analyses, proton therapy remained the more attractive strategy, either dominating photon therapy or having a very low cost per quality-adjust life year gained. Probabilistic sensitivity analysis illustrated the domination of proton therapy over photon therapy in 96.4% of simulations. CONCLUSIONSBy using current risk estimates and data on required capital investments, the current study indicated that proton therapy is a cost-effective strategy for the management of pediatric patients with medulloblastoma compared with standard of care photon therapy. Cancer 2013;119:4299-4307. (c) 2013 American Cancer Society. C1 [Vega, Raymond B. Mailhot; Michalski, Jeff] Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO USA. [Kim, Jane] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Bussiere, Marc; Tarbell, Nancy J.; Yock, Torunn; MacDonald, Shannon M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Hattangadi, Jona] Univ Calif San Diego, Dept Radiat Oncol, San Diego, CA 92103 USA. [Hollander, Abby] Washington Univ, Sch Med, Dept Pediat Endocrinol, St Louis, MO USA. RP MacDonald, SM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 100 Blossom St, Boston, MA 02114 USA. EM smacdonald@partners.org FU American Society for Therapeutic Radiology and Oncology; Massachusetts General Hospital, Proton Therapy Research and Treatment Center [C06 CA059267] FX Dr. Mailhot Vega was supported by a medical student fellowship from the American Society for Therapeutic Radiology and Oncology. The project was in part supported by the Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center. NR 44 TC 21 Z9 22 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD DEC 15 PY 2013 VL 119 IS 24 BP 4299 EP 4307 DI 10.1002/cncr.28322 PG 9 WC Oncology SC Oncology GA 295BP UT WOS:000330091900014 ER PT J AU Cleeland, CS Zhao, FM Chang, VT Sloan, JA O'Mara, AM Gilman, PB Weiss, M Mendoza, TR Lee, JW Fisch, MJ AF Cleeland, Charles S. Zhao, Fengmin Chang, Victor T. Sloan, Jeff A. O'Mara, Ann M. Gilman, Paul B. Weiss, Matthias Mendoza, Tito R. Lee, Ju-Whei Fisch, Michael J. TI The Symptom Burden of Cancer: Evidence for a Core Set of Cancer-Related and Treatment-Related Symptoms From the Eastern Cooperative Oncology Group Symptom Outcomes and Practice Patterns Study SO CANCER LA English DT Article DE symptoms; symptom assessment; cancer; symptom management; M. D. Anderson Symptom Inventory; MDASI ID MULTIPLE SYMPTOMS; METASTATIC CANCER; PAIN; SEVERITY; MODERATE; MILD; RECOMMENDATIONS; INTERFERENCE; OUTPATIENTS; PREVALENCE AB BACKGROUND: A set of common cancer-related and treatment-related symptoms has been proposed for quality of care assessment and clinical research. Using data from a large, multicenter, prospective study, the authors assessed the effects of disease site and stage on the percentages of patients rating these proposed symptoms as moderate to severe. METHODSThe severity of 13 symptoms proposed to represent core oncology symptoms was rated by 3106 ambulatory patients with cancer of the breast, prostate, colon/rectum, or lung, regardless of disease stage or phase of care; 2801 patients (90%) repeated the assessment 4 to 5 weeks later. RESULTSAt the time of the initial assessment, approximately 33% of the patients reported3 symptoms in the moderate-to-severe range; 11 of the 13 symptoms were rated as moderate to severe by at least 10% of all patients and 6 were rated as moderate to severe by at least 20% of those receiving active treatment. Fatigue/tiredness was the most severe symptom, followed by disturbed sleep, pain, dry mouth, and numbness/tingling. More patients with lung cancer and patients receiving active treatment reported moderate to severe symptoms. Percentages of symptomatic patients increased by disease stage, less adequate response to therapy, and declining Eastern Cooperative Oncology Group performance status. The percentages of patients reporting moderate to severe symptoms were stable across both assessments. CONCLUSIONSThe results of the current study support a core set of moderate to severe symptoms that are common across outpatients with solid tumors, that can guide consideration of progression-free survival as a trial outcome, and that should be considered in clinical care and in assessments of quality of care and treatment benefit. Cancer 2013;119:4333-4340. (c) 2013 American Cancer Society. C1 [Cleeland, Charles S.] Univ Texas MD Anderson Canc Ctr, Dept Symptom Res, Houston, TX 77030 USA. [Zhao, Fengmin] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Chang, Victor T.] Rutgers Univ Med & Dent New Jersey, Vet Affairs New Jersey Hlth Care Syst, E Orange, NJ USA. [Sloan, Jeff A.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. [O'Mara, Ann M.] NCI, Community Oncol & Prevent Trials Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. [Gilman, Paul B.] Main Line Hematol Oncol Associates, Lankenau Canc Ctr, Wynnewood, PA USA. [Weiss, Matthias] Marshfield Clin Fdn Med Res & Educ, Dept Hematol Oncol Northern Div, Marshfield, WI USA. [Fisch, Michael J.] Univ Texas MD Anderson Canc Ctr, Dept Gen Oncol, Houston, TX 77030 USA. RP Cleeland, CS (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Symptom Res, 1515 Holcombe Blvd,Unit 1450, Houston, TX 77030 USA. EM ccleeland@mdanderson.org FU National Cancer Institute/National Institutes of Health [CA37403, CA15488, CA13650, CA35412, CA063847]; MD Anderson Cancer Center Support Grant [P30 CA016672]; [R01 CA026582] FX Supported by grants from the National Cancer Institute/National Institutes of Health, including U10 grants CA37403, CA15488, CA13650, CA35412, and CA063847 to the Eastern Cooperative Oncology Group; R01 CA026582 to Dr. Cleeland; and MD Anderson Cancer Center Support Grant P30 CA016672. Neither the National Cancer Institute nor the National Institutes of Health had any role in the study design, data collection, analysis, interpretation, or preparation of this article. NR 20 TC 39 Z9 39 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD DEC 15 PY 2013 VL 119 IS 24 BP 4333 EP 4340 DI 10.1002/cncr.28376 PG 8 WC Oncology SC Oncology GA 295BP UT WOS:000330091900018 PM 24114037 ER PT J AU Kluenemann, HH Nutt, JG Davis, MY Thomas, D AF Kluenemann, Hans H. Nutt, John G. Davis, Marie Y. Bird, Thomas D. TI Parkinsonism syndrome in heterozygotes for Niemann-Pick C1 SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE Parkinson disease; Niemann-Pick C disease; Parkinsonism; Genetics; Lysosomal storage; Gaucher disease ID DISEASE; GENE AB Niemann-Pick C (NPC) disease is a rare autosomal recessive lipid storage disorder. We report here the unique occurrence of three adult heterozygous carriers of mutations in the NPC1 gene who also have a parkinsonism syndrome. This suggests the possibility that mutations in NPC1 could be a risk factor for Parkinson's disease similar to the phenomenon that is now recognized with Gaucher disease and the glucocerebrosidase (GBA) gene. This report should be a stimulus for larger more detailed epidemiological studies. (c) 2013 Elsevier B.V. All rights reserved. C1 [Kluenemann, Hans H.] Univ Regensburg, Dept Psychiat, D-93053 Regensburg, Germany. [Nutt, John G.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Davis, Marie Y.; Bird, Thomas D.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Bird, Thomas D.] VA Puget Sound Hlth Care Syst, GRECC, Seattle, WA USA. RP Thomas, D (reprint author), 1660 S Columbian Way,S-182-GRECC, Seattle, WA 98108 USA. EM tomnroz@uw.edu FU Veterans Affairs research and fellowship funds; National Parkinson Foundation; NIH; Michael J. Fox Foundation; Ceregene FX The authors acknowledge Veterans Affairs research and fellowship funds, National Parkinson Foundation, NIH, Michael J. Fox Foundation, and Ceregene. NR 7 TC 9 Z9 9 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X EI 1878-5883 J9 J NEUROL SCI JI J. Neurol. Sci. PD DEC 15 PY 2013 VL 335 IS 1-2 BP 219 EP 220 DI 10.1016/j.jns.2013.08.033 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 274HH UT WOS:000328596900040 PM 24035292 ER PT J AU Peraino, JS Schenk, M Li, GY Zhang, HP Farkash, EA Sachs, DH Huang, CA Duran-Struuck, R Wang, ZR AF Peraino, Jaclyn Stromp Schenk, Marian Li, Guoying Zhang, Huiping Farkash, Evan A. Sachs, David H. Huang, Christene A. Duran-Struuck, Raimon Wang, Zhirui TI Development of a diphtheria toxin-based recombinant porcine IL-2 fusion toxin for depleting porcine CD25(+) cells SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE Porcine IL-2; Fusion toxin; Diphtheria toxin; Regulatory T cell; Pichia pastoris expression ID REGULATORY T-CELLS; PICHIA-PASTORIS; IMMUNOTOXIN; EXPRESSION AB Regulatory T cells (Tregs) have been widely recognized as crucial players in controlling immune responses. Because their major role is to ensure that the immune system is not over reactive, Tregs have been the focus of multiple research studies including those investigating transplantation tolerance, autoimmunity and cancer treatment. On their surface Tregs constitutively express CD25, a high affinity receptor for the cytokine interleukin-2 (IL-2). The reagents constructed in this study were generated by genetically linking porcine IL-2 to the truncated diphtheria toxin (DT390). This reagent functions by first binding to the cell surface via the porcine IL-2/porcine CD25 interaction then the DT390 domain facilitates internalization followed by inhibition of protein synthesis resulting in cell death. Four versions of the porcine IL-2 fusion toxin were designed in an interest to find the most effective isoform: 1) monovalent glycosylated porcine IL-2 fusion toxin (Gly); 2) monovalent non-N-glycosylated porcine IL-2 fusion toxin (NonGly); 3) bivalent glycosylated porcine IL-2 fusion toxin (Bi-Gly); 4) bivalent non-N-glycosylated porcine IL-2 fusion toxin (Bi-NonGly). Using a porcine CD25(+) B cell lymphoma cell line (LCL13271) in vitro analysis of the fusion toxins' ability to inhibit protein synthesis demonstrated that the Bi-NonGly fusion toxin is the most efficient reagent. These in vitro results are consistent with binding affinity as the Bi-NonGly fusion toxin binds strongest to CD25 on the same LCL13271 cells. The Bi-Gly fusion toxin significantly prolonged the survival (p = 0.028) of tumor-bearing NOD/SCID IL-2 receptor gamma(-/-) mice injected with LCL13271 cells compared with untreated controls. This recombinant protein has great potential to function as a useful tool for in vivo depletion of porcine CD25(+) cells for studying immune regulation. (C) 2013 Elsevier B.V. All rights reserved. C1 [Peraino, Jaclyn Stromp; Schenk, Marian; Li, Guoying; Zhang, Huiping; Farkash, Evan A.; Sachs, David H.; Huang, Christene A.; Duran-Struuck, Raimon; Wang, Zhirui] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. [Peraino, Jaclyn Stromp; Schenk, Marian; Li, Guoying; Zhang, Huiping; Farkash, Evan A.; Sachs, David H.; Huang, Christene A.; Duran-Struuck, Raimon; Wang, Zhirui] Harvard Univ, Sch Med, Boston, MA USA. [Peraino, Jaclyn Stromp; Li, Guoying; Zhang, Huiping; Sachs, David H.; Huang, Christene A.; Wang, Zhirui] DF HCC MGH Recombinant Prot Express & Purificat C, Boston, MA USA. [Farkash, Evan A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02129 USA. RP Wang, ZR (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bldg 149-6113,13th St, Boston, MA 02129 USA. EM zhirui.wang@tbrc.mgh.harvard.edu FU Dana Farber/Harvard Cancer Center Core development grant; NIH [R01AI084657] FX The work was supported in part by Dana Farber/Harvard Cancer Center Core development grant and by NIH grant R01AI084657 (CAH). We would like to thank Angimmune LLC for kindly providing the diphtheria toxin resistant yeast P. pastoris strain and the codon-optimized DT390 DNA. We would like to thank Drs. Lucia Madariaga and Sabastian Michel for intensive manuscript review. NR 13 TC 2 Z9 2 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 EI 1872-7905 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD DEC 15 PY 2013 VL 398 BP 33 EP 43 DI 10.1016/j.jim.2013.09.006 PG 11 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 280EM UT WOS:000329011500004 PM 24055128 ER PT J AU Gourdain, P Boucau, J Kourjian, G Lai, NY Duong, E Le Gall, S AF Gourdain, Pauline Boucau, Julie Kourjian, Georgio Lai, Nicole Y. Duong, Ellen Le Gall, Sylvie TI A real-time killing assay to follow viral epitope presentation to CD8 T cells SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE HIV; Antigen processing; CD8 T cells; Real-time killing assay; Cytotoxicity; Kinetics ID IMMUNODEFICIENCY-VIRUS TYPE-1; FLOW-CYTOMETRIC ASSAY; MEDIATED CYTOTOXICITY; HIV-1 INFECTION; LYSISPOT ASSAY; IMMUNE ESCAPE; TARGET-CELLS; RESPONSES; GLUCOSE-6-PHOSPHATE-DEHYDROGENASE; QUANTIFICATION AB The ability of cytotoxic T lymphocytes (CTL) to clear virus-infected cells requires the presentation of viral peptides intracellularly processed and displayed by major histocompatibility complex class I. Assays to measure CTL-mediated killing often use peptides exogenously added onto target cells - which does not account for epitope processing - or follow killing of infected cells at a single time point. In this study we established a real-time fluorogenic cytotoxic assay that measures the release of the Glucose-6-phosphate-dehydrogenase by dying target cells every 5 min after addition of CTL. It has comparable sensitivity to (51)chromium-based killing assay with the additional advantage of incorporating the kinetics of epitope presentation. We showed that HIV infection of immortalized or primary CD4 T cells leads to asynchronous killing by two CTL clones specific for epitopes located in different proteins. Real-time monitoring of killing of virus-infected cells will enable identification of immune responses efficiently preventing virus dissemination. (C) 2013 Elsevier B.V. All rights reserved. C1 [Le Gall, Sylvie] MIT, Ragon Inst MGH, Cambridge, MA 02139 USA. [Le Gall, Sylvie] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Le Gall, S (reprint author), MIT, Ragon Inst MGH, 400 Technol Sq, Cambridge, MA 02139 USA. EM sylvie_legall@hms.harvard.edu FU NIAID [A1084753, A1084106] FX This study was supported by grants A1084753 and A1084106 from NIAID. NR 44 TC 3 Z9 3 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 EI 1872-7905 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD DEC 15 PY 2013 VL 398 BP 60 EP 67 DI 10.1016/j.jim.2013.09.009 PG 8 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 280EM UT WOS:000329011500007 PM 24060536 ER PT J AU Harrison, DC Ibrahim, MA Weyman, AE Kuller, LH Blot, WJ Miller, DE AF Harrison, Donald C. Ibrahim, Michel A. Weyman, Arthur E. Kuller, Lewis H. Blot, William J. Miller, David E. TI The Bjork-Shiley Convexo-Concave Heart Valve Experience from the Perspective of the Supervisory Panel SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID OUTLET STRUT FRACTURE; TILTING DISK VALVE; FOLLOW-UP; RADIOGRAPHIC DETECTION; LEG SEPARATIONS; MITRAL-VALVES; REOPERATION; COHORT; RISK; REPLACEMENT AB The 20-year activities of a medical supervisory panel appointed under the terms of a settlement agreement of the Bowling v. Pfizer class action suit involving the Bjork-Shiley convexo-concave (BSCC) heart valve are detailed. Of approximately 86,000 valves implanted, catastrophic failure of the valve was reported in 663 patients from 1978 to 2012. In 1994, a 7-member medical panel consisting of cardiologists, cardiovascular surgeons, epidemiologists, and a nontechnical chairman was appointed by the federal court. The panel collected clinical and manufacturing data, supported epidemiologic studies assessing risk factors for valve fracture, and developed guidelines for payment for explanting potentially defective valves in patients. Three sets of guidelines, based on comparisons of estimated risks of valve fracture versus risks of valve replacement surgery, were issued by the panel to help guide patients and their physicians in decisions about explanting valves. In addition, the panel supported research directed at identifying valves at risk for outlet strut fracture. The primary techniques evaluated included analyzing acoustic signals from the valves, imaging valves for potential cracks in the struts, and structural analyses of Bjork-Shiley convexo-concave valves, but none proved applicable for large-scale surveillance of the patient population. The panel also became a patient advocate and acted as an intermediary between the manufacturer and the attorneys initiating the legal settlement. The panel's experiences may help inform future strategies for guideline development for other medical devices or procedures involving risk-benefit comparisons. (C) 2013 Elsevier Inc. C1 [Harrison, Donald C.] Univ Cincinnati, Acad Hlth Ctr, Dept Med, Cincinnati, OH 45221 USA. [Ibrahim, Michel A.] Johns Hopkins Bloomberg Sch Publ Hlth, Div Epidemiol, Baltimore, MD USA. [Weyman, Arthur E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Kuller, Lewis H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Blot, William J.] Vanderbilt Univ, Med Ctr, Dept Med, Ingram Canc Ctr, Nashville, TN USA. [Miller, David E.] Bowling Pfizer Settlement Fund, Cincinnati, OH USA. RP Harrison, DC (reprint author), Univ Cincinnati, Acad Hlth Ctr, Dept Med, Cincinnati, OH 45221 USA. EM don@clsvc.com NR 33 TC 3 Z9 3 U1 2 U2 7 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 15 PY 2013 VL 112 IS 12 BP 1921 EP 1931 DI 10.1016/j.amjcard.2013.08.020 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 277DN UT WOS:000328799200013 PM 24063829 ER PT J AU Burk, M Moore, V Glassman, P Good, CB Emmendorfer, T Leadholm, TC Cunningham, F AF Burk, Muriel Moore, Von Glassman, Peter Good, Chester B. Emmendorfer, Thomas Leadholm, Thomas C. Cunningham, Francesca TI Medication-use evaluation with a Web application SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article ID DRUG-USE EVALUATION; INTERVENTIONS; SYSTEM; TRIAL AB Purpose. A Web-based application for coordinating medication-use evaluation (MUE) initiatives within the Veterans Affairs (VA) health care system is described. Summary. The MUE Tracker (MUET) software program was created to improve VA's ability to conduct national medication-related interventions throughout its network of 147 medical centers. MUET initiatives are centrally coordinated by the VA Center for Medication Safety (VAMedSAFE), which monitors the agency's integrated databases for indications of suboptimal prescribing or drug therapy monitoring and adverse treatment outcomes. When a pharmacovigilance signal is detected,. VAMedSAFE identifies "trigger groups" of at-risk veterans and uploads patient lists to the secure MUET application, where locally designated personnel (typically pharmacists) can access and use the data to target risk-reduction efforts. Local data on patient-specific interventions are stored in a centralized database and regularly updated to enable tracking and reporting for surveillance and quality-improvement purposes; aggregated data can be further analyzed for provider education and benchmarking. In a three-year pilot project, the MUET program was found effective in promoting improved prescribing of erythropoiesis-stimulating agents (ESAs) and enhanced laboratory monitoring of ESA-treated patients in all specified trigger groups. The MUET initiative has since been expanded to target other high-risk drugs, and efforts are underway to refine the tool for broader utility. Conclusion. The MUET application has enabled the increased standardization of medication safety initiatives across the VA system and may serve as a useful model for the development of pharmacovigilance tools by other large integrated health care systems. C1 [Burk, Muriel; Cunningham, Francesca] VA Ctr Medicat Safety, Hines, IL 60141 USA. [Moore, Von] VA Northern Indiana Hlth Care Syst, VA Ctr Medicat Safety, Marion, IN USA. [Glassman, Peter] VA Greater Los Angeles Healthcare Syst, Div Gen Internal Med, VA Ctr Medicat Safety, West Los Angeles, CA USA. [Good, Chester B.] VA Pittsburgh Healthcare Syst, Div Gen Internal Med, VA Ctr Medicat Safety, Pittsburgh, PA USA. [Emmendorfer, Thomas] VA Pharm Benefits Management Serv, Hines, IL USA. [Leadholm, Thomas C.] VA Ctr Medicat Safety, VA Consolidated Mail Outpatient Pharm, Dexter, MI USA. RP Burk, M (reprint author), VA Ctr Medicat Safety, 1st Ave 1 Block North Cermak Rd,Bldg 37,Room 139, Hines, IL 60141 USA. EM muriel.burk@va.gov NR 16 TC 1 Z9 2 U1 0 U2 5 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 EI 1535-2900 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD DEC 15 PY 2013 VL 70 IS 24 BP 2226 EP 2234 DI 10.2146/ajhp130252 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 274ER UT WOS:000328589500011 PM 24296845 ER PT J AU Fischer, SEJ Pan, Q Breen, PC Qi, Y Shi, Z Zhang, C Ruvkun, G AF Fischer, Sylvia E. J. Pan, Qi Breen, Peter C. Qi, Yan Shi, Zhen Zhang, Chi Ruvkun, Gary TI Multiple small RNA pathways regulate the silencing of repeated and foreign genes in C. elegans SO GENES & DEVELOPMENT LA English DT Article DE RNA silencing; transgene; siRNA; RNAi; C. elegans ID CAENORHABDITIS-ELEGANS; BINDING PROTEINS; INTERFERENCE; GERMLINE; EXPRESSION; SIRNA; AMPLIFICATION; BIOGENESIS; REVEALS; DSRNA AB Gene segments from other organisms, such as viruses, are detected as foreign and targeted for silencing by RNAi pathways. A deep-sequencing map of the small RNA response to repeated transgenes introduced to Caenorhabditis elegans revealed that specific segments are targeted by siRNAs. Silencing of the foreign gene segments depends on an antiviral response that involves changes in active and silent chromatin modifications and altered levels of antisense siRNAs. Distinct Argonaute proteins target foreign genes for silencing or protection against silencing. We used a repeated transgene in a genome-wide screen to identify gene disruptions that enhance silencing of foreign genetic elements and identified 69 genes. These genes cluster in four groups based on overlapping sets of coexpressed genes, including a group of germline-expressed genes that are likely coregulated by the E2F transcription factor. Many of the gene inactivations enhance exogenous RNAi. About half of the 69 genes have roles in endogenous RNAi pathways that regulate diverse processes, including silencing of duplicated genes and transposons and chromosome segregation. Of these newly identified genes, several are required for siRNA biogenesis or stability in the oocyte-specific ERGO-1 pathway, including eri-12, encoding an interactor of the RNAi-defective protein RDE-10, and ntl-9/CNOT9, one of several CCR4/NOT complex genes that we identified. The conserved ARF-like small GTPase ARL-8 is required specifically for primary siRNA biogenesis or stability in the sperm-specific ALG-3/4 endogenous RNAi pathway. C1 [Fischer, Sylvia E. J.; Pan, Qi; Breen, Peter C.; Qi, Yan; Shi, Zhen; Zhang, Chi; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Fischer, Sylvia E. J.; Pan, Qi; Breen, Peter C.; Qi, Yan; Shi, Zhen; Zhang, Chi; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu FU National Institutes of Health [GM44619]; Leukemia and Lymphoma Society Career Development Post-doctoral Fellowship [5560-05]; EMBO Long-Term Fellowship [ALTF 929-2003]; Massachusetts General Hospital Executive Committee of Research Fund for Medical Discovery fellowship awards FX We thank Shohei Mitani and the National Bioresource Project (Japan) for deletion strains, and the Caenorhabditis Genetics Center for strains. We thank Dennis Kim, Yuval Tabach, and Xiaoyun Wu for advice and discussions, and Tai Montgomery for reagents. This work was supported by National Institutes of Health grant GM44619 (to G. R.), Leukemia and Lymphoma Society Career Development Post-doctoral Fellowship 5560-05 (to S.E.J.F.), EMBO Long-Term Fellowship ALTF 929-2003 (to S.E.J.F.), and Massachusetts General Hospital Executive Committee of Research Fund for Medical Discovery fellowship awards (to C.Z. and S.E.J.F). S.E.J.F. and G. R. conceived and designed the experiments. S.E.J.F., Q. P., P. C. B., and C.Z. performed the experiments. S.E.J.F. analyzed the data. Y.Q. and Z.S. provided scripts for data analysis. S.E.J.F. and G. R. wrote the paper. NR 71 TC 5 Z9 5 U1 3 U2 15 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 EI 1549-5477 J9 GENE DEV JI Genes Dev. PD DEC 15 PY 2013 VL 27 IS 24 BP 2678 EP 2695 DI 10.1101/gad.233254.113 PG 18 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 278LW UT WOS:000328892800006 PM 24352423 ER PT J AU Nillni, YI Rohan, KJ Mahon, JN Pineles, SL Zvolensky, MJ AF Nillni, Yael I. Rohan, Kelly J. Mahon, Jennifer N. Pineles, Suzanne L. Zvolensky, Michael J. TI The role of anxiety sensitivity in the experience of menstrual-related symptoms reported via daily diary SO PSYCHIATRY RESEARCH LA English DT Article DE Anxiety sensitivity; Menstrual symptoms; Menstrual cycle; Premenstrual symptoms ID PREMENSTRUAL DYSPHORIC DISORDER; CYCLE PHASE; PANIC DISORDER; DISTRESS; REACTIVITY; BURDEN; ADULTS; IMPAIRMENT; EFFICACY; HORMONES AB The current study examined the interactive effects of Anxiety Sensitivity (AS) and menstrual cycle phase in the experience of menstrual-related symptoms. Participants were 55 community women who completed prospective tracking of menstrual-related symptoms across at least one full menstrual cycle using the Daily Record of Severity of Problems (DRSP) and completed the Menstrual Distress Questionnaire (MDQ) once in their premenstrual and follicular cycle phases. Results revealed that women with higher levels of AS reported greater menstrual-related symptoms, regardless of cycle phase, as compared to women with lower levels of AS. These findings suggest that AS may be an important psychological factor involved in the experience of psychological and somatic symptoms across the menstrual cycle. Results are consistent with previous literature documenting the role of AS in menstrual-related symptoms as well as in other physical health conditions. Published by Elsevier Ireland Ltd. C1 [Nillni, Yael I.; Rohan, Kelly J.; Mahon, Jennifer N.] Univ Vermont, Burlington, VT USA. [Nillni, Yael I.; Pineles, Suzanne L.] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA USA. [Nillni, Yael I.; Pineles, Suzanne L.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Zvolensky, Michael J.] Univ Houston, Houston, TX USA. [Zvolensky, Michael J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Nillni, YI (reprint author), Vet Affairs Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, 150 South Huntington Ave 116B-3, Boston, MA 02130 USA. EM yael.nillni2@va.gov FU National Institute of Mental Health Dissertation grant [1R36MH086170]; VA Career Development Award, Department of Veterans Affairs FX This work is based on the doctoral dissertation of the first author and was supported by a National Institute of Mental Health Dissertation grant awarded to Yael I. Nillni (1R36MH086170). Additional support also was provided to Suzanne Pineles, Ph.D., through a VA Career Development Award, Department of Veterans Affairs. NR 36 TC 4 Z9 5 U1 0 U2 4 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 15 PY 2013 VL 210 IS 2 BP 564 EP 569 DI 10.1016/j.psychres.2013.07.016 PG 6 WC Psychiatry SC Psychiatry GA 273EU UT WOS:000328518600031 PM 23910240 ER PT J AU Schumacher, S Schnyder, U Furrer, M Mueller-Pfeiffer, C Wilhelm, FH Moergeli, H Oe, M Martin-Soelch, C AF Schumacher, Sonja Schnyder, Ulrich Furrer, Michael Mueller-Pfeiffer, Christoph Wilhelm, Frank H. Moergeli, Hanspeter Oe, Misari Martin-Soelch, Chantal TI Startle reactivity in the long-term after severe accidental injury: Preliminary data SO PSYCHIATRY RESEARCH LA English DT Article DE Startle; Trauma; Post-traumatic stress disorder (PTSD); Psychophysiology ID POSTTRAUMATIC-STRESS-DISORDER; MOTOR-VEHICLE ACCIDENTS; ADMINISTERED PTSD SCALE; PHYSIOLOGICAL-RESPONSES; VIETNAM VETERANS; LOUD TONES; TRAUMA SURVIVORS; ACOUSTIC STARTLE; VICTIMS; REFLEX AB An exaggerated startle response is one of the core hyperarousal symptoms of posttraumatic stress disorder (PTSD). Heightened startle eye-blink magnitude and reduced habituation of this response in PTSD patients have been reported in several studies. However, it is unclear whether this is an enduring characteristic of individuals vulnerable for PTSD or to which degree trauma-exposed individuals who do not develop PTSD also show exaggerated startle. Thirteen accident survivors with remitted PTSD, 12 trauma controls, and 16 non-trauma controls were examined. Four measures of startle reactivity were analyzed in response to 15 bursts of white noise (95 dB, 50 ms): eye-blink magnitude, eye-blink onset latency, skin conductance response, and heart rate response. The eye-blink reflex was measured over the left musculus orbicularis oculi. Reactivity and habituation were analyzed using linear mixed models. Remitted PTSD subjects did not differ from non-trauma controls regarding any of the startle reactivity or habituation measures. Unexpectedly, trauma controls showed larger eye-blink magnitude than non. trauma controls. These results suggest that the exaggerated startle response disappears after remission from PTSD. Further, they suggest that psychologically resilient trauma survivors might show a PTSD-like pattern of exaggerated physiological startle even many years after a traumatic event. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Schumacher, Sonja; Schnyder, Ulrich; Furrer, Michael; Mueller-Pfeiffer, Christoph; Moergeli, Hanspeter; Oe, Misari; Martin-Soelch, Chantal] Univ Zurich Hosp, Dept Psychiat & Psychotherapy, CH-8091 Zurich, Switzerland. [Furrer, Michael] Psychiat Hosp Konigsfelden, Brugg, Switzerland. [Mueller-Pfeiffer, Christoph] Psychiat Serv Cty St Gallen North, Ctr Educ & Res COEUR, Wil, Switzerland. [Mueller-Pfeiffer, Christoph] Massachusetts Gen Hosp, Div Psychiat, Dept Psychol, Boston, MA 02114 USA. [Mueller-Pfeiffer, Christoph] Harvard Univ, Sch Med, Boston, MA USA. [Wilhelm, Frank H.] Salzburg Univ, Dept Psychol, Div Clin Psychol Psychotherapy & Hlth Psychol, A-5020 Salzburg, Austria. [Oe, Misari] Kurume Univ, Dept Neuropsychiat, Sch Med, Fukuoka, Japan. [Martin-Soelch, Chantal] Univ Fribourg, Dept Psychol, Div Clin & Hlth Psychol, CH-1700 Fribourg, Switzerland. RP Schumacher, S (reprint author), Univ Zurich Hosp, Dept Psychiat & Psychotherapy, Haldenbachstr 18, CH-8091 Zurich, Switzerland. EM sonja.schumacher@usz.ch NR 36 TC 4 Z9 4 U1 9 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 15 PY 2013 VL 210 IS 2 BP 570 EP 574 DI 10.1016/j.psychres.2013.06.034 PG 5 WC Psychiatry SC Psychiatry GA 273EU UT WOS:000328518600032 PM 23870491 ER PT J AU Seo, YJ Muench, L Reid, A Chen, JZ Kang, YN Hooker, JM Volkow, ND Fowler, JS Kim, SW AF Seo, Young Jun Muench, Lisa Reid, Alicia Chen, Jinzhu Kang, Yeona Hooker, Jacob M. Volkow, Nora D. Fowler, Joanna S. Kim, Sung Won TI Radionuclide labeling and evaluation of candidate radioligands for PET imaging of histone deacetylase in the brain SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Carbon-11; Positron emission tomography; SAHA; Brain; Epigenetics; Brain permeability ID TRICHOSTATIN-A; INHIBITORS; POTENT; RADIOSYNTHESIS; MECHANISMS; DISORDERS; EFFICIENT; ESTERS; MS-275 AB Histone deacetylases (HDACs) regulate gene expression by inducing conformational changes in chromatin. Ever since the discovery of a naturally occurring HDAC inhibitor, trichostatin A (TSA) stimulated the recent development of suberoylanilide (SAHA, Zolinza (R)), HDAC has become an important molecular target for drug development. This has created the need to develop specific in vivo radioligands to study epigenetic regulation and HDAC engagement for drug development for diseases including cancer and disorders. 6-([F-18]Fluoroacetamido)-1-hexanoicanilide ([F-18]FAHA) was recently developed as a HDAC substrate and shows moderate blood-brain barrier (BBB) permeability and specific signal (by metabolic trapping/or deacetylation) but rapid metabolism. Here, we report the radiosynthesis of two carbon-11 labeled candidate radiotracers (substrate-and inhibitor-based radioligand) for HDAC and their evaluation in non-human primate brain. PET studies showed very low brain uptake and rapid metabolism of both labeled compounds but revealed a surprising enhancement of brain penetration by F for H substitution when comparing one of these to [F-18]FAHA. Further structural refinement is needed for the development of brain-penetrant, metabolically stable HDAC radiotracers and to understand the role of fluorine substitution on brain penetration. Published by Elsevier Ltd. C1 [Seo, Young Jun; Chen, Jinzhu; Kang, Yeona; Fowler, Joanna S.] Brookhaven Natl Lab, Dept Biosci, Upton, NY 11973 USA. [Seo, Young Jun] Chonbuk Natl Univ, Dept Chem, Jeonju 561756, South Korea. [Muench, Lisa; Volkow, Nora D.; Kim, Sung Won] NIAAA, Lab Neuroimaging, Bethesda, MD 20892 USA. [Reid, Alicia] CUNY Medgar Evers Coll, Dept Phys Environm & Comp Sci, Brooklyn, NY 11225 USA. [Hooker, Jacob M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. [Volkow, Nora D.] NIDA, Rockville, MD 20852 USA. RP Hooker, JM (reprint author), NIAAA, 10 Ctr Dr,Rm B2L304, Bethesda, MD 20892 USA. EM hooker@nmr.mgh.harvard.edu; sunny.kim@nih.gov OI Hooker, Jacob/0000-0002-9394-7708 FU DOE [BR KP1503010]; NIH [1R01DA030321]; U.S. Department of Energy [DEAC02-98CH10886]; National Institute on Alcohol Abuse and Alcoholism FX This work was supported by DOE grant B&R KP1503010 and NIH grant 1R01DA030321. In addition, the work at Brookhaven National Laboratory was performed under contract DEAC02-98CH10886 with the U.S. Department of Energy, and with infrastructure support from its Office of Biological and Environmental Research. Salary support for SWK and LM was provided by the intramural program of the National Institute on Alcohol Abuse and Alcoholism. We are grateful to the PET radiotracer and imaging team at BNL (Dr. Michael Schueller, David Alexoff, Colleen Shea, Youwen Xu, Pauline Carter, Payton King, Barbara Hubbard and Don Warner) for carrying out primate imaging experiments. We used two computational chemistry programs available in the Center for Molecular Modeling (http://cmm.cit.nih.gov) and the Helix Systems (http://helix.nih.gov) at the National Institutes of Health, Bethesda, MD. NR 30 TC 10 Z9 10 U1 3 U2 18 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X EI 1464-3405 J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD DEC 15 PY 2013 VL 23 IS 24 BP 6700 EP 6705 DI 10.1016/j.bmcl.2013.10.038 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 263DU UT WOS:000327787700033 PM 24210501 ER PT J AU Magill, SS Klompas, M Balk, R Burns, SM Deutschman, CS Diekema, D Fridkin, S Greene, L Guh, A Gutterman, D Hammer, B Henderson, D Hess, D Hill, NS Horan, T Kollef, M Levy, M Septimus, E VanAntwerpen, C Wright, D Lipsett, P AF Magill, Shelley S. Klompas, Michael Balk, Robert Burns, Suzanne M. Deutschman, Clifford S. Diekema, Daniel Fridkin, Scott Greene, Linda Guh, Alice Gutterman, David Hammer, Beth Henderson, David Hess, Dean Hill, Nicholas S. Horan, Teresa Kollef, Marin Levy, Mitchell Septimus, Edward VanAntwerpen, Carole Wright, Don Lipsett, Pamela TI Developing a New, National Approach to Surveillance for Ventilator-Associated Events: Executive Summary SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material DE ventilator-associated pneumonia; intensive care unit; epidemiology; public health; critical care; mechanical ventilation C1 [Magill, Shelley S.; Fridkin, Scott; Guh, Alice; Horan, Teresa] Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Atlanta, GA 30329 USA. [Klompas, Michael] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Klompas, Michael] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Klompas, Michael] Brigham & Womens Hosp, Infect Control Dept, Boston, MA 02115 USA. [Klompas, Michael] Soc Healthcare Epidemiol Amer, Arlington, VA USA. [Balk, Robert] Rush Univ, Sch Med, Div Pulm & Crit Care Med, Chicago, IL 60612 USA. [Balk, Robert; Burns, Suzanne M.; Deutschman, Clifford S.; Gutterman, David; Hammer, Beth; Hill, Nicholas S.; Kollef, Marin; Levy, Mitchell; Lipsett, Pamela] Crit Care Soc Collaborat Amer Assoc Crit Care Nur, Charlottesville, VA USA. [Burns, Suzanne M.] Univ Virginia, Sch Nursing Crit & Acute Care, Charlottesville, VA USA. [Deutschman, Clifford S.] Univ Penn, Perelman Sch Med, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA. [Diekema, Daniel] Univ Iowa, Carver Coll Med, Div Infect Dis, Iowa City, IA USA. [Diekema, Daniel] Healthcare Infect Control Practices Advisory Comm, Atlanta, GA USA. [Greene, Linda] Rochester Gen Hlth Syst, Infect Prevent & Control Dept, Rochester, NY USA. [Greene, Linda] Assoc Profess Infect Control & Epidemiol, Washington, DC USA. [Gutterman, David] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Hammer, Beth] Zablocki VA Med Ctr, Dept Cardiol, Milwaukee, WI USA. [Henderson, David] NIH, Hosp Epidemiol & Qual Improvement, Ctr Clin, Bethesda, MD 20892 USA. [Hess, Dean] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Hess, Dean] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. [Hess, Dean] Amer Assoc Resp Care, Irving, TX USA. [Hill, Nicholas S.] Tufts Med Ctr, Div Pulm & Crit Care Med, Boston, MA USA. [Kollef, Marin] Washington Univ, Div Pulm & Crit Care Med, St Louis, MO USA. [Levy, Mitchell] Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Div Pulm Crit Care & Sleep, Providence, RI 02903 USA. [Septimus, Edward] Texas A&M Hlth Sci Ctr, Dept Internal Med, College Stn, TX USA. [Septimus, Edward] Infect Dis Soc Amer, Arlington, VA USA. [VanAntwerpen, Carole] New York State Dept Hlth, Bur Healthcare Associated Infect, Albany, NY USA. [VanAntwerpen, Carole] Council State & Terr Epidemiologists, Atlanta, GA USA. [Wright, Don] US Dept HHS, Off Dis Prevent & Hlth Promot, Washington, DC 20201 USA. [Lipsett, Pamela] Johns Hopkins Univ, Sch Med, Dept Surg Anesthesiol & Crit Care Med, Baltimore, MD USA. RP Magill, SS (reprint author), Ctr Dis Control & Prevent, Div Healthcare Qual Promot, 1600 Clifton Rd,MS A-24, Atlanta, GA 30329 USA. EM smagill@cdc.gov NR 2 TC 12 Z9 13 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2013 VL 57 IS 12 BP 1742 EP 1746 DI 10.1093/cid/cit577 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 262FT UT WOS:000327720400013 PM 24280662 ER PT J AU Ruf, V Holzem, C Peyman, T Walz, G Blackwell, TK Neumann-Haefelin, E AF Ruf, Vanessa Holzem, Christina Peyman, Tobias Walz, Gerd Blackwell, T. Keith Neumann-Haefelin, Elke TI TORC2 signaling antagonizes SKN-1 to induce C. elegans mesendodermal embryonic development SO DEVELOPMENTAL BIOLOGY LA English DT Article DE TOR signaling; RICTOR; SGK-1; SKN-1; Development; C. elegans ID RESTRICTION-INDUCED LONGEVITY; BOX FACTOR TBX-35; COMPLEX 2 TORC2; CAENORHABDITIS-ELEGANS; GATA-FACTOR; LIFE-SPAN; GENE-EXPRESSION; MTOR COMPLEX; KINASE; GROWTH AB The evolutionarily conserved target of rapamycin (TOR) kinase controls fundamental metabolic processes to support cell and tissue growth. TOR functions within the context of two distinct complexes, TORC1 and TORC2. TORC2, with its specific component Rictor, has been recently implicated in aging and regulation of growth and metabolism. Here, we identify rict-1/Rictor as a regulator of embryonic development in C. elegans. The transcription factor skn-1 establishes development of the mesendoderm in embryos, and is required for cellular homeostasis and longevity in adults. Loss of maternal skn-1 function leads to mis-specification of the mesendodermal precursor and failure to form intestine and pharynx. We found that genetic inactivation of rict-1 suppressed skn-1-associated lethality by restoring mesendodermal specification in skn-1 deficient embryos. Inactivation of other TORC2 but not TORC1 components also partially rescued skn-1 embryonic lethality. The SGK-1 kinase mediated these functions downstream of rict-1/TORC2, as a sgk-1 gain-of-function mutant suppressed the rict-1 mutant phenotype. These data indicate that TORC2 and SGK-1 antagonize SKN-1 during embryonic development. (C) 2013 Elsevier Inc. All rights reserved. C1 [Ruf, Vanessa; Holzem, Christina; Peyman, Tobias; Walz, Gerd; Neumann-Haefelin, Elke] Univ Hosp Freiburg, Div Renal, Dept Med, D-79106 Freiburg, Germany. [Walz, Gerd] Univ Freiburg, Ctr Biol Signaling Studies Bioss, D-79104 Freiburg, Germany. [Blackwell, T. Keith] Harvard Stem Cell Inst, Joslin Diabet Ctr, Boston, MA 02215 USA. [Blackwell, T. Keith] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02215 USA. RP Blackwell, TK (reprint author), Harvard Stem Cell Inst, Joslin Diabet Ctr, Boston, MA 02215 USA. EM keith.blackwell@joslin.harvard.edu; elke.neumann-haefelin@uniklinik-freiburg.de FU DFG [KFO 201]; European Social fund; Ministry of Science, Research, and Arts Baden-Wurttemberg; NIH [GM062891]; Ellison Medical Foundation; BMBF [01ES0708] FX This study was supported by grants from the DFG (KFO 201), the European Social fund and the Ministry of Science, Research, and Arts Baden-Wurttemberg to ENH, and by grant GM062891 from the NIH and an Ellison Medical Foundation Senior Scholar Award to TKB. GW was funded by BMBF (01ES0708). NR 74 TC 4 Z9 9 U1 1 U2 16 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 EI 1095-564X J9 DEV BIOL JI Dev. Biol. PD DEC 15 PY 2013 VL 384 IS 2 BP 214 EP 227 DI 10.1016/j.ydbio.2013.08.011 PG 14 WC Developmental Biology SC Developmental Biology GA 261OE UT WOS:000327673700006 PM 23973804 ER PT J AU Yu, CE Cudaback, E Foraker, J Thomson, Z Leong, L Lutz, F Gill, JA Saxton, A Kraemer, B Navas, P Keene, CD Montine, T Bekris, LM AF Yu, Chang-En Cudaback, Eiron Foraker, Jessica Thomson, Zachary Leong, Lesley Lutz, Franziska Gill, James Anthony Saxton, Aleen Kraemer, Brian Navas, Patrick Keene, C. Dirk Montine, Thomas Bekris, Lynn M. TI Epigenetic signature and enhancer activity of the human APOE gene SO HUMAN MOLECULAR GENETICS LA English DT Article ID ONSET ALZHEIMERS-DISEASE; HUMAN APOLIPOPROTEIN-E; CENTRAL-NERVOUS-SYSTEM; DNA METHYLATION; CPG-ISLANDS; COMPREHENSIVE ANALYSIS; TARGETED REPLACEMENT; TRANSGENIC MICE; E POLYMORPHISM; BRAIN AB The human apolipoprotein E (APOE) gene plays an important role in lipid metabolism. It has three common genetic variants, alleles epsilon 2/epsilon 3/epsilon 4, which translate into three protein isoforms of apoE2, E3 and epsilon 4. These isoforms can differentially influence total serum cholesterol levels; therefore, APOE has been linked with cardiovascular disease. Additionally, its 14 allele is strongly associated with the risk of Alzheimer's disease (AD), whereas the 12 allele appears to have a modest protective effect for AD. Despite decades of research having illuminated multiple functional differences among the three apoE isoforms, the precise mechanisms through which different APOE alleles modify diseases risk remain incompletely understood. In this study, we examined the genomic structure of APOE in search for properties that may contribute novel biological consequences to the risk of disease. We identify one such element in the epsilon 2/epsilon 3/epsilon 4 allele-carrying 3'-exon of APOE. We show that this exon is imbedded in a well-defined CpG island (CGI) that is highly methylated in the human postmortem brain. We demonstrate that this APOE CGI exhibits transcriptional enhancer/silencer activity. We provide evidence that this APOE CGI differentially modulates expression of genes at the APOE locus in a cell type-, DNA methylation-and epsilon 2/epsilon 3/epsilon 4 allele-specific manner. These findings implicate a novel functional role for a 3'-exon CGI and support a modified mechanism of action for APOE in disease risk, involving not only the protein isoforms but also an epigenetically regulated transcriptional program at the APOE locus driven by the APOE CGI. C1 [Yu, Chang-En; Foraker, Jessica; Thomson, Zachary; Leong, Lesley; Gill, James Anthony; Saxton, Aleen; Kraemer, Brian; Bekris, Lynn M.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Yu, Chang-En; Foraker, Jessica; Lutz, Franziska; Kraemer, Brian; Bekris, Lynn M.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. [Navas, Patrick] Univ Washington, Div Med Genet, Seattle, WA 98195 USA. [Cudaback, Eiron; Keene, C. Dirk; Montine, Thomas] Univ Washington, Dept Pathol, Div Neuropathol, Seattle, WA 98195 USA. RP Yu, CE (reprint author), VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. EM changeyu@uw.edu RI Keene, Christopher/N-1806-2015 FU US Department of Veterans Affairs Office of Research and Development Biomedical Laboratory Research Program; National Institute of Health/NIH [P50 AG05136, K99 AG34214, T32 AG000258]; Nancy and Buster Alvord Endowment FX This work was supported in part by the US Department of Veterans Affairs Office of Research and Development Biomedical Laboratory Research Program; the National Institute of Health/NIH grants (P50 AG05136, K99 AG34214, T32 AG000258); and the Nancy and Buster Alvord Endowment. NR 70 TC 21 Z9 22 U1 0 U2 18 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC 15 PY 2013 VL 22 IS 24 BP 5036 EP 5047 DI 10.1093/hmg/ddt354 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 259QY UT WOS:000327542600014 PM 23892237 ER PT J AU Kim, AY Page, K AF Kim, Arthur Y. Page, Kimberly TI Hepatitis C Virus Serosorting in People Who Inject Drugs: Sorting Out the Details SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material DE injection drugs; testing; nucleic acid test ID YOUNG-ADULTS; INFECTION; USERS; RISK; SYRINGES; UPDATE C1 [Kim, Arthur Y.] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. [Kim, Arthur Y.] Harvard Univ, Sch Med, Boston, MA USA. [Page, Kimberly] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Kim, AY (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, Cox 5,55 Fruit St, Boston, MA 02114 USA. EM akim1@partners.org OI Page, Kimberly/0000-0002-7120-1673 FU NIAID NIH HHS [U19 AI066345]; NIDA NIH HHS [R01 DA016017, R01 DA 033541, R01 DA031056, R01 DA033541, R01DA016017, R01 DA031059, R01 DA 031059, R01 DA 031056]; NIDDK NIH HHS [P30 DK026743] NR 18 TC 1 Z9 1 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2013 VL 208 IS 12 BP 1929 EP 1931 DI 10.1093/infdis/jit526 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 259RS UT WOS:000327544600001 PM 24136791 ER PT J AU Amiri-Kordestani, L Mena, E Lindenberg, ML Kurdziel, K Choyke, P Patronas, N Frye, R Lin, N Bala, S Fojo, T Bates, S AF Amiri-Kordestani, L. Mena, E. Lindenberg, M. L. Kurdziel, K. Choyke, P. Patronas, N. Frye, R. Lin, N. Bala, S. Fojo, T. Bates, S. TI 18F-FLT-PET/CT for the prediction of response to ANG-1005 therapy in patients with brain metastases from breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 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 2013 VL 73 SU 24 MA P4-01-09 DI 10.1158/0008-5472.SABCS13-P4-01-09 PG 1 WC Oncology SC Oncology GA V40RY UT WOS:000209496901265 ER PT J AU Balko, JM Giltnane, JM Schwarz, LJ Sanders, ME Wang, K Harris, LN Lin, NU Miller, VA Stephens, PJ Yelensky, R Pinto, JA Gomez, H Arteaga, CL AF Balko, J. M. Giltnane, J. M. Schwarz, L. J. Sanders, M. E. Wang, K. Harris, L. N. Lin, N. U. Miller, V. A. Stephens, P. J. Yelensky, R. Pinto, J. A. Gomez, H. Arteaga, C. L. TI JAK2 amplifications are enriched in triple negative breast cancers (TNBCs) after neoadjuvant chemotherapy and predict poor prognosis SO CANCER RESEARCH LA English DT Meeting Abstract C1 Vanderbilt Univ, Nashville, TN 37235 USA. Fdn Med, Cambridge, MA USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Oncosalud, Lima, Peru. Inst Nacl Enfermedades Neoplas, Lima, Peru. 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 2013 VL 73 SU 24 MA S6-01 DI 10.1158/0008-5472.SABCS13-S6-01 PG 1 WC Oncology SC Oncology GA V40RY UT WOS:000209496903136 ER PT J AU Baselga, J Morales, SM Awada, A Blum, JL Tan, AR Ewertz, M Cortes, J Moy, B Ruddy, KJ Haddad, T Ciruelos, EM Vuylsteke, P Ebbinghaus, S Im, E Eaton, L Prathiraja, K Gause, C Mauro, D Rugo, HS AF Baselga, J. Morales, S. M. Awada, A. Blum, J. L. Tan, A. R. Ewertz, M. Cortes, J. Moy, B. Ruddy, K. J. Haddad, T. Ciruelos, E. M. Vuylsteke, P. Ebbinghaus, S. Im, E. Eaton, L. Prathiraja, K. Gause, C. Mauro, D. Rugo, H. S. TI A phase 2 study of ridaforolimus (RIDA) and dalotuzumab (DALO) in estrogen receptor positive (ER plus ) breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Mem Sloan Kettering, New York, NY USA. H de Lleida Arnau de Vilanova, Lerida, Spain. Inst Jules Bordet, B-1000 Brussels, Belgium. US Oncol, Texas Oncol, Baylor Sammons Canc Ctr, Dallas, TX USA. Canc Inst New Jersey, New Brunswick, NJ USA. Odense Univ Hosp, DK-5000 Odense, Denmark. Vall dHebron Univ Hosp, Barcelona, Spain. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Minnesota, Mason Clin Canc Ctr, Minneapolis, MN USA. Hosp 12 Octubre, E-28041 Madrid, Spain. Clin St Elizabeth, Namur, Belgium. Merck Res Labs, N Wales, PA USA. UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 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 2013 VL 73 SU 24 MA P2-16-04 DI 10.1158/0008-5472.SABCS13-P2-16-04 PG 1 WC Oncology SC Oncology GA V40RY UT WOS:000209496901053 ER PT J AU Burstein, HJ AF Burstein, H. J. TI Update on management of ER positive metastatic breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Burstein, H. J.] 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 2013 VL 73 SU 24 MA ES09-1 DI 10.1158/0008-5472.SABCS13-ES09-1 PG 2 WC Oncology SC Oncology GA V40RY UT WOS:000209496900026 ER PT J AU Dienstmann, R Adamo, B Vidal, L Dees, EC Chia, S Mayer, EL Baney, TS Dhuria, S Sen, SK Papoutsakis, D Cameron, S Infante, JR AF Dienstmann, R. Adamo, B. Vidal, L. Dees, E. C. Chia, S. Mayer, E. L. Baney, T. S. Dhuria, S. Sen, S. K. Papoutsakis, D. Cameron, S. Infante, J. R. TI Phase Ib study of LCL161, an oral antagonist of inhibitor of apoptosis proteins, in combination with weekly paclitaxel in patients with advanced solid tumors: Safety and efficacy results, including breast cancer cohort SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Autonoma Barcelona, Vail dHebron Univ Hosp, E-08193 Barcelona, Spain. Hosp Clin Barcelona, Barcelona, Spain. Univ Policlin Modena, Azienda Osped, Modena, Italy. 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 Faber Canc Inst, Boston, MA USA. Novartis Pharmaceut, E Hanover, NJ USA. Novartis Pharmaceut, Cambridge, MA USA. Tennessee Oncol PLLC, Sarah Cannon Res Inst, 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 2013 VL 73 SU 24 MA PD5-7 DI 10.1158/0008-5472.SABCS13-PD5-7 PG 1 WC Oncology SC Oncology GA V40RY UT WOS:000209496903087 ER PT J AU Dieras, V Yardley, D Romieu, G Valero, V Isakoff, S Koeppen, H Thurm, H Teng, M Campone, M Mocci, S AF Dieras, V. Yardley, D. Romieu, G. Valero, V. Isakoff, S. Koeppen, H. Thurm, H. Teng, M. Campone, M. Mocci, S. TI A randomized, phase II, multicenter, double-blind, placebo-controlled trial evaluating onartuzumab with or without bevacizumab in combination with weekly paclitaxel in locally recurrent or metastatic triple-negative breast cancer (TNBC) SO CANCER RESEARCH LA English DT Meeting Abstract C1 Inst Curie, Paris, France. SCRI Tennessee Oncol PLLC, Nashville, TN USA. ICM Inst Canc Montpellier, Montpellier, France. UT MD Anderson Canc Ctr, Houston, TX USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Genentech Inc, San Francisco, CA 94080 USA. Inst Cancerol Ouest, St Herbalin Nantes, France. 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 2013 VL 73 SU 24 MA P2-16-01 DI 10.1158/0008-5472.SABCS13-P2-16-01 PG 1 WC Oncology SC Oncology GA V40RY UT WOS:000209496901050 ER PT J AU Elias, A Modi, S Krop, IE Pegram, M Ipe, D Guardino, EA Althaus, B LoRusso, PL AF Elias, A. Modi, S. Krop, I. E. Pegram, M. Ipe, D. Guardino, E. A. Althaus, B. LoRusso, P. L. TI Results from a phase 2a study of trastuzumab emtansine, paclitaxel, and pertuzumab in patients with HER2-positive metastatic breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Colorado Hosp, Auriora, CO USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Stanford Canc Inst, Palo Alto, CA USA. Genentech Inc, San Francisco, CA 94080 USA. Karmanos Canc Inst, Detroit, MI 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 2013 VL 73 SU 24 MA P4-12-09 DI 10.1158/0008-5472.SABCS13-P4-12-09 PG 2 WC Oncology SC Oncology GA V40RY UT WOS:000209496902016 ER PT J AU Frank, ES Price, KN Colten, ME Fax, RG Levine, MA Matyka, C Dowton, AA Barry, W Winer, EP Partridge, AH AF Frank, E. S. Price, K. N. Colten, M. E. Fax, R. G. Levine, M. A. Matyka, C. Dowton, A. A. Barry, W. T. Winer, E. P. Partridge, A. H. TI Sharing clinical trial results with patient participants: A project of the Dana Farber/Harvard Cancer Center (DF/HCC) breast cancer research advocacy group SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Breast Canc Advocacy Grp, DF HCC Breast Canc Program, Boston, 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 2013 VL 73 SU 24 MA P4-18-01 DI 10.1158/0008-5472.SABCS13-P4-18-01 PG 2 WC Oncology SC Oncology GA V40RY UT WOS:000209496902071 ER PT J AU Golshan, M Weingart, SN Losk, K Hirshfield-Bartek, J Cutone, L Abeita, J Kadish, S Bunnell, C AF Golshan, M. Weingart, S. N. Losk, K. Hirshfield-Bartek, J. Cutone, L. Abeita, J. Kadish, S. Bunnell, C. TI Process-of-care: Elucidating delays in surgical treatment of breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Golshan, M.; Weingart, S. N.; Losk, K.; Hirshfield-Bartek, J.; Cutone, L.; Abeita, J.; Kadish, S.; Bunnell, C.] Dana Farber Brigham & Womens Canc Ctr, Boston, 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 2013 VL 73 SU 24 MA P5-13-15 DI 10.1158/0008-5472.SABCS13-P5-13-15 PG 2 WC Oncology SC Oncology GA V40RY UT WOS:000209496902201 ER PT J AU Gucalp, A Morris, PG Zhou, XK Giri, DD Lyengar, NM Heckman-Stoddard, BM Dunn, B Garber, JE Crew, KD Hershman, DL Nangia, JR Cook, ED Brown, PH Dannenberg, AJ Hudis, CA AF Gucalp, A. Morris, P. G. Zhou, X. K. Giri, D. D. Lyengar, N. M. Heckman-Stoddard, B. M. Dunn, B. Garber, J. E. Crew, K. D. Hershman, D. L. Nangia, J. R. Cook, E. D. Brown, P. H. Dannenberg, A. J. Hudis, C. A. TI A multicenter phase II study of docosahexaenoic acid (DHA) in triple negative breast cancer (TNBC) survivors SO CANCER RESEARCH LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Columbia Univ, Med Ctr, New York, NY USA. Baylor Coll Med, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Weill Cornell Med Coll, New York, NY USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. EM gucalpa@mskcc.org 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 2013 VL 73 SU 24 MA OT3-3-01 DI 10.1158/0008-5472.SABCS13-OT3-3-01 PG 2 WC Oncology SC Oncology GA V40RY UT WOS:000209496900100 ER PT J AU Horton, JK Blitzblau, RC Yoo, S Georgiade, GS Geradts, J Baker, JA Chang, Z Broadwater, G Barry, W Duffy, EA Hwang, ES AF Horton, J. K. Blitzblau, R. C. Yoo, S. Georgiade, G. S. Geradts, J. Baker, J. A. Chang, Z. Broadwater, G. Barry, W. Duffy, E. A. Hwang, E. S. TI Preoperative single-fraction partial breast radiotherapy - Initial results from a novel phase I dose-escalation protocol with exploration of radiation response biomarkers SO CANCER RESEARCH LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Durham, NC 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 2013 VL 73 SU 24 MA P5-14-04 DI 10.1158/0008-5472.SABCS13-P5-14-04 PG 2 WC Oncology SC Oncology GA V40RY UT WOS:000209496902205 ER PT J AU Isakoff, SJ Cruz, C Garber, J Lluch, A Fidalgo, JAP Tung, N Fernandez, C Kahatt, C Szyldergemajn, S Matos-Pita, AS Baselga, J Balmana, J AF Isakoff, S. J. Cruz, C. Garber, J. Lluch, A. Perez Fidalgo, J. A. Tung, N. Fernandez, C. Kahatt, C. Szyldergemajn, S. Soto Matos-Pita, A. Baselga, J. Balmana, J. TI Multicenter phase II trial of the novel compound PM01183 (P) in BRCA1/2-associated or unselected metastatic breast cancer (MBC) SO CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Hosp Valle De Hebron, Barcelona, Spain. Dana Farber Canc Inst, Boston, MA 02115 USA. Hosp Clin Valencia, Valencia, Spain. Beth Israel Deaconesse Med Ctr, Boston, MA USA. PharmaMar, Madrid, Spain. Mem Sloan Kettering Canc Ctr, New York, NY USA. NR 0 TC 0 Z9 0 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 2013 VL 73 SU 24 MA OT1-4-01 DI 10.1158/0008-5472.SABCS13-OT1-4-01 PG 2 WC Oncology SC Oncology GA V40RY UT WOS:000209496900051 ER PT J AU Juric, D Saura, C Cervantes, A Kurkjian, C Patel, MR Sachdev, J Mayer, I Krop, IE Oliveira, M Sanabria, S Cheeti, S Lin, RS Graham, RA Wilson, TR Parmar, H Hsu, JY Von Hoff, DD Baselga, J AF Juric, D. Saura, C. Cervantes, A. Kurkjian, C. Patel, M. R. Sachdev, J. Mayer, I. Krop, I. E. Oliveira, M. Sanabria, S. Cheeti, S. Lin, R. S. Graham, R. A. Wilson, T. R. Parmar, H. Hsu, J. Y. Von Hoff, D. D. Baselga, J. TI Ph1b study of the PI3K inhibitor GDC-0032 in combination with fulvestrant in patients with hormone receptor-positive advanced breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Vall dHebron Univ Hosp, Vall dHebron Inst Oncol, Barcelona, Spain. Univ Valencia, Inst Hlth Res INCLIVA, Valencia, Spain. Univ Oklahoma, Oklahoma City, OK USA. Florida Canc Specialists, Sarah Cannon Res Inst, Sarasota, FL USA. TGen, Virginia G Piper Canc Ctr, Scottsdale, AZ USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Genentech Inc, San Francisco, CA 94080 USA. 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 2013 VL 73 SU 24 MA PD1-3 DI 10.1158/0008-5472.SABCS13-PD1-3 PG 1 WC Oncology SC Oncology GA V40RY UT WOS:000209496903052 ER PT J AU Juric, D Gonzalez-Angulo, AM Burris, HA Schuler, M Schellens, J Berlin, J Gupta, A Seggewiss-Bernhardt, R Adamo, B Gil-Martin, M Bootle, D Boehm, M De Buck, S Demanse, D Quadt, C Baselga, J AF Juric, D. Gonzalez-Angulo, A. M. Burris, H. A. Schuler, M. Schellens, J. Berlin, J. Gupta, A. Seggewiss-Bernhardt, R. Adamo, B. Gil-Martin, M. Bootle, D. Boehm, M. De Buck, S. Demanse, D. Quadt, C. Baselga, J. TI Preliminary safety, pharmacokinetics and anti-tumor activity of BYL719, an alpha-specific P13K inhibitor in combination with fulvestrant: Results from a phase I study SO CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Sarah Cannon Res Inst, Nashville, TN USA. Univ Hosp Essen, Essen, Germany. Netherlands Canc Inst, Amsterdam, Netherlands. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Oxford Univ Hosp NHS Trust, Oxford, England. Univ Hosp Wurzburg, CCC MF, Wurzburg, Germany. Vall dHebron Univ Hosp, Barcelona, Spain. Catalan Inst Oncol, Barcelona, Spain. Novartis Pharma AG, Basel, Switzerland. Novartis Pharmaceut, E Hanover, NJ USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 2 Z9 2 U1 3 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2013 VL 73 SU 24 MA P2-16-14 DI 10.1158/0008-5472.SABCS13-P2-16-14 PG 1 WC Oncology SC Oncology GA V40RY UT WOS:000209496901063 ER PT J AU Krop, I Lin, N Blackwell, K Guardino, E Huober, J Lu, M Miles, D Samant, M Welslau, M Dieras, V AF Krop, I. Lin, N. Blackwell, K. Guardino, E. Huober, J. Lu, M. Miles, D. Samant, M. Welslau, M. Dieras, V. TI Efficacy and safety of trastuzumab emtansine (T-DM1) vs lapatinib plus capecitabine (XL) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) and central nervous system (CNS) metastases: Results from a retrospective exploratory analysis of EMILIA SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Genentech Inc, San Francisco, CA USA. Breast Ctr, St Gallen, Switzerland. Mt Vernon Canc Ctr, Northwood, Middx, England. Inst Curie, F-75231 Paris, France. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2013 VL 73 SU 24 MA P4-12-27 DI 10.1158/0008-5472.SABCS13-P4-12-27 PG 2 WC Oncology SC Oncology GA V40RY UT WOS:000209496902033 ER PT J AU Krop, IE Suter, TM Dirix, L Romieu, G Zamagni, C Citron, ML Campone, M Dang, CT Xu, N Smitt, M Gianni, L AF Krop, I. E. Suter, T. M. Dirix, L. Romieu, G. Zamagni, C. Citron, M. L. Campone, M. Dang, C. T. Xu, N. Smitt, M. Gianni, L. TI Cardiac safety of trastuzumab emtansine (T-DM1) following anthracycline-based chemotherapy as (neo) adjuvant therapy for human epidermal growth factor receptor 2-positive (HER2+) early-stage breast cancer (EBC): Final data from TDM4874g SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Hosp Bern, Swiss Cardiovasc Ctr, CH-3010 Bern, Switzerland. Sint Augustinus Hosp, Antwerp, Belgium. ICM Val dAurelle, Montpellier, France. Policlin S Orsola Malpighi Hosp, Bologna, Italy. Hofstra North Shore LIJ Sch Med, Hyde Pk, NY USA. Inst Cancerol Ouest Rene Gauducheau, St Herblain, France. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Genentech Inc, San Francisco, CA 94080 USA. Hosp San Raffaele, I-20132 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 2013 VL 73 SU 24 MA P2-15-03 DI 10.1158/0008-5472.SABCS13-P2-15-03 PG 2 WC Oncology SC Oncology GA V40RY UT WOS:000209496901048 ER PT J AU Lin, NU Whitesell, L Gelman, R Mayer, E Krop, IE Santagata, S Lowe, A Proia, D Farooq, S Brown, M Lannone, M Lindquist, S Winer, EP AF Lin, N. U. Whitesell, L. Gelman, R. Mayer, E. Krop, I. E. Santagata, S. Lowe, A. Proia, D. Farooq, S. Brown, M. Lannone, M. Lindquist, S. Winer, E. P. TI Randomized phase II study of fulvestrant with or without ganetespib in patients (pts) with hormone receptor (HR)-positive metastatic breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Whitehead Inst, Cambridge, MA 02142 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Synta Pharmaceut, Lexington, MA USA. EM nlin@partners.org 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 2013 VL 73 SU 24 MA OT3-2-05 DI 10.1158/0008-5472.SABCS13-OT3-2-05 PG 2 WC Oncology SC Oncology GA V40RY UT WOS:000209496900093 ER PT J AU Lluch-Hernandez, A Simon, AR Huang, CS Castan, JC Ruiz-Borrego, M Telli, M Ismail-Khan, R Parton, M Tseng, LM Chen, SC Schmid, P Mayer, I Hurvitz, S Garcia-Estevez, L Atienza, R Wu, M Cameron, S Beck, JT Bardia, A AF Lluch-Hernandez, A. Ruiz Simon, A. Huang, C-S Cortes Castan, J. Ruiz-Borrego, M. Telli, M. Ismail-Khan, R. Parton, M. Tseng, L-M Chen, S-C Schmid, P. Mayer, I. Hurvitz, S. Garcia-Estevez, L. Atienza, R. Wu, M. Cameron, S. Beck, J. T. Bardia, A. TI A phase II randomized, open-label, neoadjuvant study of LCL161, an oral antagonist of inhibitor of apoptosis proteins, in combination with paclitaxel in patients with triple-negative breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Hosp Clin Univ Valencia, Valencia, Spain. Inst Valenciano Oncol, Valencia, Spain. Natl Taiwan Univ Hosp, Taipei, Taiwan. Vall dHebron Univ Hosp, Barcelona, Spain. Hosp Virgen del Rocio, Seville, Spain. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Royal Marsden Hosp, London SW3 6JJ, England. Inst Canc Res, London SW3 6JB, England. Taipei Vet Gen Hosp, Taipei, Taiwan. Chang Gung Mem Hosp, Taipei 10591, Taiwan. Royal Sussex Cty Hosp, Brighton, E Sussex, England. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. Hosp Sanchinarro, Madrid, Spain. Novartis Pharmaceut, E Hanover, NJ USA. Nova Pharmaceut Corp, Cambridge, MA USA. Highlands Oncol Grp, Fayetteville, AR USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 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 2013 VL 73 SU 24 MA OT1-4-04 DI 10.1158/0008-5472.SABCS13-OT1-4-04 PG 2 WC Oncology SC Oncology GA V40RY UT WOS:000209496900054 ER PT J AU Matulonis, UA Wulf, G Cantley, L Mills, G Lasonde, B Atkinson, T Whalen, C Isakoff, SJ Westin, S Bell-McGuinn, K Winer, E AF Matulonis, U. A. Wulf, G. Cantley, L. Mills, G. Lasonde, B. Atkinson, T. Whalen, C. Isakoff, S. J. Westin, S. Bell-McGuinn, K. Winer, E. TI Phase I study of the combination of BKM120 and olaparib for the treatment of high grade serous ovarian cancer (HGSC) and triple negative breast cancer (TNBC) SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. Weill Cornell Med Coll, New York, NY USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. EM umatulonis@partners.org 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 2013 VL 73 SU 24 MA OT1-4-02 DI 10.1158/0008-5472.SABCS13-OT1-4-02 PG 2 WC Oncology SC Oncology GA V40RY UT WOS:000209496900052 ER PT J AU Mayer, IA Bardia, A Dickler, MN Manning, HC Mahmood, U Ulaner, GA Hager, JH Rix, P Zack, N Maneval, EC Chen, I Baselga, J Arteaga, CL AF Mayer, I. A. Bardia, A. Dickler, M. N. Manning, H. C. Mahmood, U. Ulaner, G. A. Hager, J. H. Rix, P. Zack, N. Maneval, E. C. Chen, I. Baselga, J. Arteaga, C. L. TI Phase I study of ARN-810, a novel selective estrogen receptor degrader, in post-menopausal women with locally advanced or metastatic estrogen receptor positive breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Aragon Pharmaceut, San Diego, CA 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 2013 VL 73 SU 24 MA OT3-2-07 DI 10.1158/0008-5472.SABCS13-OT3-2-07 PG 2 WC Oncology SC Oncology GA V40RY UT WOS:000209496900095 ER PT J AU Mayer, IA Jovanovic, B Abramson, VG Mayer, EL Sanders, ME Bardia, A Dillon, PM Kuba, MG Carpenter, JT Chang, JC Lehmann, BD Meszoely, IM Grau, A Shyr, Y Arteaga, CL Chen, X Pietenpol, JA AF Mayer, I. A. Jovanovic, B. Abramson, V. G. Mayer, E. L. Sanders, M. E. Bardia, A. Dillon, P. M. Kuba, M. G. Carpenter, J. T. Chang, J. C. Lehmann, B. D. Meszoely, I. M. Grau, A. Shyr, Y. Arteaga, C. L. Chen, X. (S) Pietenpol, J. A. TI A randomized phase II neoadjuvant study of cisplatin, paclitaxel with or without everolimus (an mTOR inhibitor) in patients with stage II/III triple-negative breast cancer (TNBC) SO CANCER RESEARCH LA English DT Meeting Abstract C1 Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Dana Farber Canc Inst, Boston, MD USA. Univ Virginia, Hlth Sci Ctr, Charlottesville, VA USA. Univ Alabama Birmingham, Birmingham, AL USA. Methodist Hosp, Res Inst, Houston, TX 77030 USA. Massachusetts Gen Hosp, Boston, MD USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2013 VL 73 SU 24 MA PD1-6 DI 10.1158/0008-5472.SABCS13-PD1-6 PG 2 WC Oncology SC Oncology GA V40RY UT WOS:000209496903055 ER PT J AU Meier, CA Vaz-Luis, I Seah, D Macrae, EM Burstein, HJ Sohl, J Arvold, ND Winer, EP Lin, NU AF Meier, C. A. Vaz-Luis, I. Seah, D. Macrae, E. M. Burstein, H. J. Sohl, J. Arvold, N. D. Winer, E. P. Lin, N. U. TI Impact of tumor subtype on clinical features, treatment, and clinical outcomes among breast cancer patients with central nervous system disease SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA USA. Arthur G James Canc Hosp, Columbus, OH USA. Richard J Solove Res Inst, Columbus, OH 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 2013 VL 73 SU 24 MA P6-11-09 DI 10.1158/0008-5472.SABCS13-P6-11-09 PG 1 WC Oncology SC Oncology GA V40RY UT WOS:000209496903031 ER PT J AU Metzger, O Procter, M de Azambuja, E Krieguer, M Gelber, RD Piccart, M AF Metzger Filho, O. Procter, M. de Azambuja, E. Krieguer, M. Gelber, R. D. Piccart, M. TI Trastuzumab re-treatment following adjuvant trastuzumab and the importance of distant disease-free interval: The HERA trial experience SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA USA. Inst Jules Bordet, Frontier Sci, Brussels, Belgium. 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 2013 VL 73 SU 24 MA P2-15-04 DI 10.1158/0008-5472.SABCS13-P2-15-04 PG 1 WC Oncology SC Oncology GA V40RY UT WOS:000209496901049 ER PT J AU Moody, SE Schinzel, AC Singh, S Izzo, F Strickland, MR Luo, LY Thomas, SR Boehm, JS Kim, SY Wang, ZC Hahn, WC AF Moody, S. E. Schinzel, A. C. Singh, S. Izzo, F. Strickland, M. R. Luo, L. Y. Thomas, S. R. Boehm, J. S. Kim, S. Y. Wang, Z. C. Hahn, W. C. TI Systematic interrogation of resistance to HER2-directed therapy identifies a survival pathway activated by PRKACA and PIM1 SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Broad Inst, Cambridge, MA USA. Duke Univ, Durham, NC USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, 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 2013 VL 73 SU 24 MA P5-08-01 DI 10.1158/0008-5472.SABCS13-P5-08-01 PG 2 WC Oncology SC Oncology GA V40RY UT WOS:000209496902136 ER PT J AU Munster, P Krop, IE Miller, K Dhindsa, N Niyijiza, C Nielsen, U Odueyungbo, A Rajarethinam, A Marande, M Campbell, K Geretti, E Reynolds, JG Hendriks, BS Wickham, T Moyo, V LoRusso, P AF Munster, P. Krop, I. E. Miller, K. Dhindsa, N. Niyijiza, C. Nielsen, U. Odueyungbo, A. Rajarethinam, A. Marande, M. Campbell, K. Geretti, E. Reynolds, J. G. Hendriks, B. S. Wickham, T. Moyo, V. LoRusso, P. TI Assessment of safety and activity in an expanded phase 1 study of MM-302, a HER2-targeted liposomal doxorubicin, in patients with advanced HER2-positive (HER2+) breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 UCSF, Helen Diller Family Compreshens Canc Ctr, San Francisco, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. Merrimack Pharmaceut Inc, Cambridge, MA USA. Karmanos Canc Inst, Detroit, MI 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 2013 VL 73 SU 24 MA P4-12-29 DI 10.1158/0008-5472.SABCS13-P4-12-29 PG 2 WC Oncology SC Oncology GA V40RY UT WOS:000209496902035 ER PT J AU Nakhlis, F Regan, MM Warren, LE Bellon, JR Yeh, ED Jacene, HA Golshan, M Duggan, MM Dominici, LS Hirshfield-Bartek, J Mullaney, EE Overmoyer, BA AF Nakhlis, F. Regan, M. M. Warren, L. E. Bellon, J. R. Yeh, E. D. Jacene, H. A. Golshan, M. Duggan, M. M. Dominici, L. S. Hirshfield-Bartek, J. Mullaney, E. E. Overmoyer, B. A. TI The impact of residual disease after preoperative systemic therapy on clinical outcomes in patients with inflammatory breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Nakhlis, F.; Regan, M. M.; Warren, L. E.; Bellon, J. R.; Yeh, E. D.; Jacene, H. A.; Golshan, M.; Duggan, M. M.; Dominici, L. S.; Hirshfield-Bartek, J.; Mullaney, E. E.; Overmoyer, B. A.] Dana Farber Brigham & Womens Canc Ctr, Boston, 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 2013 VL 73 SU 24 MA P6-12-05 DI 10.1158/0008-5472.SABCS13-P6-12-05 PG 1 WC Oncology SC Oncology GA V40RY UT WOS:000209496903039 ER PT J AU O'Sullivan, CC Holmes, E Spielmann, M Perez, EA Joensuu, H Costantino, JP Delaloge, S Rastogi, P Zardavas, D Ballman, KV de Azambuja, E Piccart-Gebhart, M Zujewski, JA Gelber, RD AF O'Sullivan, C. C. Holmes, E. Spielmann, M. Perez, E. A. Joensuu, H. Costantino, J. P. Delaloge, S. Rastogi, P. Zardavas, D. Ballman, K. V. de Azambuja, E. Piccart-Gebhart, M. Zujewski, J. A. Gelber, R. D. TI The prognosis of small HER2+breast cancers: A meta-analysis of the randomized trastuzumab trials SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. Frontier Sci Scotland, Kincraig, Inverness, Scotland. Inst Gustave Roussy, Villejuif, France. Inst Jules Bordet, B-1000 Brussels, Belgium. Mayo Clin, Jacksonville, FL 32224 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Helsinki, Cent Hosp, FIN-00014 Helsinki, Finland. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Rochester, MN 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 2013 VL 73 SU 24 MA S6-03 DI 10.1158/0008-5472.SABCS13-S6-03 PG 1 WC Oncology SC Oncology GA V40RY UT WOS:000209496903138 ER PT J AU Overmoyer, BA Regan, M Brugge, J Perou, CM Nakhlis, F Jennifer, B Heather, J Eren, YD Judith, HB Winer, E AF Overmoyer, B. A. Regan, M. Brugge, J. Perou, C. M. Nakhlis, F. Jennifer, B. Heather, J. Eren, Y. D. Judith, H-B Winer, E. TI Phase II trial of paclitaxel combined with trastuzumab and pertuzumab as preoperative therapy for HER2 positive inflammatory breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 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 2013 VL 73 SU 24 MA OT1-1-07 DI 10.1158/0008-5472.SABCS13-OT1-1-07 PG 2 WC Oncology SC Oncology GA V40RY UT WOS:000209496900038 ER PT J AU Palmer, SC Stricker, CT Panzer, SL Syrjala, KL Baker, KS McCabe, MS Rosenstein, DL Partridge, AH Arvey, SR Jacobs, LA AF Palmer, S. C. Stricker, C. T. Panzer, S. L. Syrjala, K. L. Baker, K. S. McCabe, M. S. Rosenstein, D. L. Partridge, A. H. Arvey, S. R. Jacobs, L. A. TI Survivorship care planning - When is intervention most effective? SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. LIVESTRONG Fdn, Austin, TX 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 2013 VL 73 SU 24 MA P3-08-07 DI 10.1158/0008-5472.SABCS13-P3-08-07 PG 1 WC Oncology SC Oncology GA V40RY UT WOS:000209496901172 ER PT J AU Paoletti, C Li, Y Muniz, MC Kidwell, KM Aung, K Thomas, DG Brown, ME Abramson, V Irvin, WJ Lin, NU Liu, M Nanda, R Nangia, J Storniolo, AM Traina, TA Vaklavas, C Van Poznak, CH Wolff, AC Forero, A Hayes, DF AF Paoletti, C. Li, Y. Muniz, M. C. Kidwell, K. M. Aung, K. Thomas, D. G. Brown, M. E. Abramson, V. Irvin, W. J., Jr. Lin, N. U. Liu, M. Nanda, R. Nangia, J. Storniolo, A. M. Traina, T. A. Vaklavas, C. Van Poznak, C. H. Wolff, A. C. Forero, A. Hayes, D. F. TI Significance of circulating tumor cells in metastatic triple negative breast cancer: Results of an open label, randomized, phase II trial of nanoparticle albumin-bound paclitaxel with or without the anti-death receptor 5 tigatuzumab (TBCRC 019) SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Univ Alabama Birmingham, Birmingham, AL USA. Vanderbilt Breast Canc Ctr, Nashville, TN USA. Bon Secours Canc Inst, Midlothian, VA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. Univ Chicago, Chicago, IL 60637 USA. Baylor Coll Med, Houston, TX 77030 USA. Indiana Univ, Melvin & Bran Simon Canc Ctr, Indianapolis, IN 46204 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Baltimore, 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 2013 VL 73 SU 24 MA P1-04-01 DI 10.1158/0008-5472.SABCS13-P1-04-01 PG 2 WC Oncology SC Oncology GA V40RY UT WOS:000209496900139 ER PT J AU Partridge, AH Ruddy, KJ Barry, WT Greaney, M Sprunck-Harrild, K Meyer, ME Baker, EL Ligibel, J Emmons, KM AF Partridge, A. H. Ruddy, K. J. Barry, W. T. Greaney, M. Sprunck-Harrild, K. Meyer, M. E. Baker, E. L. Ligibel, J. Emmons, K. M. TI Young and strong: A randomized trial to evaluate a program for young women with breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, 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 2013 VL 73 SU 24 MA OT2-4-02 DI 10.1158/0008-5472.SABCS13-OT2-4-02 PG 2 WC Oncology SC Oncology GA V40RY UT WOS:000209496900063 ER PT J AU Piccart-Gebhart, M Holmes, AP de Azambuja, E Di Cosimo, S Swaby, R Untch, M Jackisch, C Lang, I Smith, I Boyle, F Xu, B Barrios, C Gelber, R Eidtmann, H Baselga, J AF Piccart-Gebhart, M. Holmes, A. P. de Azambuja, E. Di Cosimo, S. Swaby, R. Untch, M. Jackisch, C. Lang, I. Smith, I. Boyle, F. Xu, B. Barrios, C. Gelber, R. Eidtmann, H. Baselga, J. TI The association between event-free survival and pathological complete response to neoadjuvant lapatinib, trastuzumab or their combination in HER2-positive breast cancer. Survival follow-up analysis of the NeoALTTO study (BIG 1-06) SO CANCER RESEARCH LA English DT Meeting Abstract C1 Inst Jules Bordet, B-1000 Brussels, Belgium. Frontier Sci Scotland Ltd, Kincraig, Kingussie, Scotland. Fdn IRCCS Ist Nazl Tumori, Milan, Italy. GlaxoSmithKline, Munich, Germany. Univ Charite, Acad Hosp, Berlin, Germany. Klinikum Offenbach, Offenbach, Germany. Natl Inst Oncol, Budapest, Hungary. Royal Marsden Hosp, London, U Arab Emirates. Inst Canc Res, London, U Arab Emirates. Mater Hosp North Sydney, Patricia Ritchie Ctr Canc Care & Res, Sydney, NSW, Australia. Univ Sydney, Sydney, NSW 2006, Australia. Chinese Acad Med Sci, Canc Hosp, Beijing 100730, Peoples R China. PUCRS Sch Med, Porto Alegre, Belgium. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Hosp Kiel, Kiel, Germany. 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 2013 VL 73 SU 24 MA S1-01 DI 10.1158/0008-5472.SABCS13-S1-01 PG 1 WC Oncology SC Oncology GA V40RY UT WOS:000209496903100 ER PT J AU Reynolds, KL Sasmit, S Moy, B Elena, B Amy, C Atul, B Aditya, B AF Reynolds, K. L. Sasmit, S. Moy, B. Elena, B. Amy, C. Atul, B. Aditya, B. TI High HER2 gene amplification and clinical outcomes in localized HER2-positive breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Reynolds, K. L.; Sasmit, S.; Moy, B.; Elena, B.; Amy, C.; Atul, B.; Aditya, B.] 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 2013 VL 73 SU 24 MA P4-12-02 DI 10.1158/0008-5472.SABCS13-P4-12-02 PG 2 WC Oncology SC Oncology GA V40RY UT WOS:000209496902010 ER PT J AU Ruddy, KJ Tolaney, SM Guo, H Dang, CT Yardley, DA Moy, B Marcom, PK Albain, KS Rugo, HS Ellis, MJ Shapira, I Wolff, AC Carey, LA Overmoyer, BA Hudis, C Krop, IE Burstein, HJ Winer, EP Partridge, AH AF Ruddy, K. J. Tolaney, S. M. Guo, H. Dang, C. T. Yardley, D. A. Moy, B. Marcom, P. K. Albain, K. S. Rugo, H. S. Ellis, M. J. Shapira, I. Wolff, A. C. Carey, L. A. Overmoyer, B. A. Hudis, C. Krop, I. E. Burstein, H. J. Winer, E. P. Partridge, A. H. TI Chemotherapy-related amenorrhea on adjuvant paclitaxel-trastuzumab (APT trial) SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Sarah Cannon Res Inst, Nashville, TN USA. Duke Univ, Med Ctr, Durham, NC USA. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Washington Univ, St Louis, MO USA. North Shore LIJ Hofstra Med Sch, Manhasset, NY USA. Johns Hopkins Kimmel Canc Ctr, Baltimore, MD 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 2013 VL 73 SU 24 MA P3-08-05 DI 10.1158/0008-5472.SABCS13-P3-08-05 PG 1 WC Oncology SC Oncology GA V40RY UT WOS:000209496901170 ER PT J AU Ruddy, KJ Baker, EL Guo, H Goldstein, MJ Winer, EP Shulman, LN Partridge, AH AF Ruddy, K. J. Baker, E. L. Guo, H. Goldstein, M. J. Winer, E. P. Shulman, L. N. Partridge, A. H. TI Randomized trial evaluating a coordinated survivorship care program for early stage breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. EM katieruddy@gmail.com 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 DEC 15 PY 2013 VL 73 SU 24 MA OT2-5-02 DI 10.1158/0008-5472.SABCS13-OT2-5-02 PG 2 WC Oncology SC Oncology GA V40RY UT WOS:000209496900065 ER PT J AU Sajjadi, AY Wanyo, CM Specht, M Schapira, L Moy, B Bardia, A Finkelstein, DM Boas, DA Carp, SA Isakoff, SJ AF Sajjadi, A. Y. Wanyo, C. M. Specht, M. Schapira, L. Moy, B. Bardia, A. Finkelstein, D. M. Boas, D. A. Carp, S. A. Isakoff, S. J. TI Normalization of compression-induced hemodynamics in patients responding to neoadjuvant chemotherapy using dynamic tomographic optical breast imaging (TOBI) 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 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 2013 VL 73 SU 24 MA P4-02-01 DI 10.1158/0008-5472.SABCS13-P4-02-01 PG 1 WC Oncology SC Oncology GA V40RY UT WOS:000209496901279 ER PT J AU Schmidt, EV Blackman, S Iannone, R Senderak, ET Railkar, RA Evelhoch, JL Mozley, PD Perez, EA McDonough, M Rimawi, M Tolaney, S Kim, SB Chung, HC AF Schmidt, E. V. Blackman, S. Iannone, R. Senderak, E. T. Railkar, R. A. Evelhoch, J. L. Mozley, P. D. Perez, E. A. McDonough, M. Rimawi, M. Tolaney, S. Kim, S-B Chung, H-C TI Limits of [18F]-FLT PET as a clinical biomarker of proliferation in breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Merck Res Labs, Whitehouse Stn, NJ USA. Seattle Genet, Seattle, WA USA. Cornell Univ Med Coll, New York, NY USA. Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. Baylor Coll Med, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Asan Med Ctr, Seoul, Song Pa, South Korea. Yonsei Univ, Seoul 120749, Seodaemun Gu, South Korea. NR 1 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 2013 VL 73 SU 24 MA P4-01-11 DI 10.1158/0008-5472.SABCS13-P4-01-11 PG 2 WC Oncology SC Oncology GA V40RY UT WOS:000209496901267 ER PT J AU Seah, DSE Scott, SM Guo, H Najita, J Lederman, R Frank, E Sohl, J Kronwitz, C Stadler, ZK Silverman, SG Peppercorn, J Winer, EP Come, SE Lin, NU AF Seah, D. S. E. Scott, S. M. Guo, H. Najita, J. Lederman, R. Frank, E. Sohl, J. Kronwitz, C. Stadler, Z. K. Silverman, S. G. Peppercorn, J. Winer, E. P. Come, S. E. Lin, N. U. TI Attitudes of medical oncologists towards research biopsies SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deconess Med Ctr, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Duke Univ, Sch Med, Durham, NC 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 2013 VL 73 SU 24 MA P4-19-01 DI 10.1158/0008-5472.SABCS13-P4-19-01 PG 2 WC Oncology SC Oncology GA V40RY UT WOS:000209496902072 ER PT J AU Shapiro, GI AF Shapiro, G. I. TI Targeting homologous recombination: Translational studies of CDK and PARP inhibitors SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Shapiro, G. I.] 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 2013 VL 73 SU 24 MA ES01-3 DI 10.1158/0008-5472.SABCS13-ES01-3 PG 2 WC Oncology SC Oncology GA V40RY UT WOS:000209496900013 ER PT J AU Sieuwerts, AM Burns, M Look, MP Meijer-Van Gelder, ME Schlicker, A Heidemann, MR Jacobs, H Wessels, L Willis, S Leyland-Jones, B Gray, K Foekens, JA Harris, RS Martens, JW AF Sieuwerts, A. M. Burns, M. Look, M. P. Meijer-Van Gelder, M. E. Schlicker, A. Heidemann, M. R. Jacobs, H. Wessels, L. Willis, S. Leyland-Jones, B. Gray, K. Foekens, J. A. Harris, R. S. Martens, J. W. TI High levels of APOBEC3B, a DNA deaminase and an enzymatic source of C-to-T transitions, are a validated marker of poor outcome in estrogen receptor-positive breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Erasmus Univ, Med Ctr, Canc Genom Netherlands, Erasmus MC Canc Inst, Rotterdam, Netherlands. Univ Minnesota, Minneapolis, MN USA. Netherlands Canc Inst, Amsterdam, Netherlands. Sanford Hlth & Res, Sioux Falls, SD 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 2013 VL 73 SU 24 MA S6-05 DI 10.1158/0008-5472.SABCS13-S6-05 PG 2 WC Oncology SC Oncology GA V40RY UT WOS:000209496903140 ER PT J AU Sikov, WM Berry, DA Perou, CM Singh, B Cirrincione, C Tolaney, S Kuzma, CS Pluard, TJ Somlo, G Port, E Golshan, M Bellon, JR Collyar, D Hahn, OM Carey, LA Hudis, C Winer, EP AF Sikov, W. M. Berry, D. A. Perou, C. M. Singh, B. Cirrincione, C. Tolaney, S. Kuzma, C. S. Pluard, T. J. Somlo, G. Port, E. Golshan, M. Bellon, J. R. Collyar, D. Hahn, O. M. Carey, L. A. Hudis, C. Winer, E. P. TI Impact of the addition of carboplatin (Cb) and/or bevacizumab (B) to neoadjuvant weekly paclitaxel (P) followed by dose-dense AC on pathologic complete response (pCR) rates in triple-negative breast cancer (TNBC): CALGB 40603 (Alliance) SO CANCER RESEARCH LA English DT Meeting Abstract C1 Miriam Hosp, Providence, RI 02906 USA. Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. NYU, Med Ctr, New York, NY 10016 USA. Alliance Stat Ctr, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Southeast Canc Control Consortium, Winston Salem, NC USA. Washington Univ, St Louis Med Ctr, St Louis, MO USA. City Hope Comprehens Canc Ctr, Duarte, CA USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Patient Advocates Res, Danville, CA USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 7 Z9 7 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 2013 VL 73 SU 24 MA S5-01 DI 10.1158/0008-5472.SABCS13-S5-01 PG 2 WC Oncology SC Oncology GA V40RY UT WOS:000209496903129 ER PT J AU Smerage, JB Barlow, WE Hayes, DF Winer, EP Leyland-Jones, B Srkalovic, G Tejwani, S Schott, AF O'Rourke, MA Lew, DL Gralow, JR Livingston, RB Hortobagyi, GN AF Smerage, J. B. Barlow, W. E. Hayes, D. F. Winer, E. P. Leyland-Jones, B. Srkalovic, G. Tejwani, S. Schott, A. F. O'Rourke, M. A. Lew, D. L. Gralow, J. R. Livingston, R. B. Hortobagyi, G. N. TI SWOG S0500-A randomized phase III trial to test the strategy of changing therapy versus maintaining therapy for metastatic breast cancer patients who have elevated circulating tumor cell (CTC) levels at first follow-up assessment SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Michigan, Ann Arbor, MI 48109 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Sanford Canc Ctr, Sioux Falls, SD USA. Sparrow Hlth Syst, Lansing, MI USA. Greenville Hlth Syst Canc Inst, Greenville, SC USA. Henry Ford Hosp, Detroit, MI 48202 USA. Univ Arizona, Ctr Canc, Tucson, AZ USA. Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. SWOG Stat Ctr, Seattle, WA USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2013 VL 73 SU 24 MA S5-07 DI 10.1158/0008-5472.SABCS13-S5-07 PG 1 WC Oncology SC Oncology GA V40RY UT WOS:000209496903134 ER PT J AU Stricker, CT Palmer, SC Panzer, SL Syrjala, KL Baker, KS McCabe, MS Rosenstein, DL Partridge, AH Arvey, SR Jacobs, LA AF Stricker, C. T. Palmer, S. C. Panzer, S. L. Syrjala, K. L. Baker, K. S. McCabe, M. S. Rosenstein, D. L. Partridge, A. H. Arvey, S. R. Jacobs, L. A. TI Breast cancer survivors' outcomes and satisfaction following delivery of a survivorship care plan: Results of a multicenter trial SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. LIVESTRONG Fdn, Austin, TX 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 2013 VL 73 SU 24 MA P3-08-02 DI 10.1158/0008-5472.SABCS13-P3-08-02 PG 1 WC Oncology SC Oncology GA V40RY UT WOS:000209496901167 ER PT J AU Taghian, AG Skolny, MN O'Toole, J Miller, CL Jammallo, LS Horick, N Elliott, K Specht, MC AF Taghian, A. G. Skolny, M. N. O'Toole, J. Miller, C. L. Jammallo, L. S. Horick, N. Elliott, K. 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.; Horick, N.; Elliott, K.; Specht, M. C.] Massachusetts Gen Hosp, Boston, MA 02114 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 2013 VL 73 SU 24 MA OT2-5-01 DI 10.1158/0008-5472.SABCS13-OT2-5-01 PG 2 WC Oncology SC Oncology GA V40RY UT WOS:000209496900064 ER PT J AU Tolaney, SM Barry, WT Dang, CT Yardley, DA Moy, B Marcom, PK Albain, KS Rugo, HS Ellis, M Shapira, I Wolff, AC Carey, LA Overmoyer, BA Partridge, AH Guo, H Hudis, CA Krop, IE Burstein, HJ Winer, EP AF Tolaney, S. M. Barry, W. T. Dang, C. T. Yardley, D. A. Moy, B. Marcom, P. K. Albain, K. S. Rugo, H. S. Ellis, M. Shapira, I. Wolff, A. C. Carey, L. A. Overmoyer, B. A. Partridge, A. H. Guo, H. Hudis, C. A. Krop, I. E. Burstein, H. J. Winer, E. P. TI A phase II study of adjuvant paclitaxel (T) and trastuzumab (H) (APT trial) for node-negative, HER2-positive breast cancer (BC) SO CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Sarah Cannon Res Inst, Nashville, TN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Duke Univ, Durham, NC USA. Loyola Univ, Maywood, IL 60153 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Washington Univ, St Louis, MO USA. Long Isl Jewish Med Ctr, New Hyde Pk, NY 11042 USA. Johns Hopkins Univ, Baltimore, MD USA. Univ N Carolina, Chaprl Hill, NC USA. NR 0 TC 5 Z9 5 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 DEC 15 PY 2013 VL 73 SU 24 MA S1-04 DI 10.1158/0008-5472.SABCS13-S1-04 PG 1 WC Oncology SC Oncology GA V40RY UT WOS:000209496903103 ER PT J AU Winer, EP AF Winer, E. P. TI HER2+breast cancer: Unresolved challenges SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Winer, E. P.] 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 2013 VL 73 SU 24 MA MS02-1 DI 10.1158/0008-5472.SABCS13-MS02-1 PG 2 WC Oncology SC Oncology GA V40RY UT WOS:000209496900031 ER PT J AU Yardley, DA Awada, A Cortes, J Burris, HA Peterson, A Bhattacharya, S Gianni, L Miller, K Winer, E AF Yardley, D. A. Awada, A. Cortes, J. Burris, H. A. Peterson, A. Bhattacharya, S. Gianni, L. Miller, K. Winer, E. TI A phase 2 randomized, double-blind, placebo-controlled multicenter trial evaluating the efficacy and safety of enzalutamide in combination with exemestane in estrogen or progesterone receptor-positive and HER2 non-amplified advanced breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 Sarah Cannon Res Inst, Nashville, TN USA. Tennessee Oncol, Nashville, TN USA. Univ Libre Bruxelles, Inst Jules Bordet, Brussels, Belgium. Univ Hosp Vall Hebron, Barcelona, Spain. Medivation Inc, San Francisco, CA USA. Hosp San Raffaele, I-20132 Milan, Italy. Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. EM amy.peterson@medivation.com 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 2013 VL 73 SU 24 MA OT3-2-01 DI 10.1158/0008-5472.SABCS13-OT3-2-01 PG 2 WC Oncology SC Oncology GA V40RY UT WOS:000209496900089 ER PT J AU Zardavas, D Fumagalli, D Borwn, DN Desmedt, C Metzger, O Piccart, M Sotiriou, C Michieles, S Loi, S AF Zardavas, D. Fumagalli, D. Borwn, D. N. Desmedt, C. Metzger-Filho, O. Piccart, M. Sotiriou, C. Michieles, S. Loi, S. TI Understanding the biology and prognosis of PIK3CA gene mutations in primary breast cancer using gene expression profiling: A pooled analysis SO CANCER RESEARCH LA English DT Meeting Abstract C1 Inst Jules Bordet, B-1000 Brussels, Belgium. Inst Jules Bordet, Canc Translat Res Lab JC Heuson, B-1000 Brussels, Belgium. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Paris 11, Gustave Roussy, Villejuif, France. Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. RI Loi, Sherene/H-1979-2016 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 2013 VL 73 SU 24 MA P2-11-02 DI 10.1158/0008-5472.SABCS13-P2-11-02 PG 1 WC Oncology SC Oncology GA V40RY UT WOS:000209496901010 ER PT J AU Lane, JM Tare, A Cade, BE Chen, TH Punjabi, NM Gottlieb, DJ Scheer, FAJL Redline, S Saxena, R AF Lane, Jacqueline M. Tare, Archana Cade, Brian E. Chen, Ting-hsu Punjabi, Naresh M. Gottlieb, Daniel J. Scheer, Frank A. J. L. Redline, Susan Saxena, Richa TI Common Variants in CLOCK Are Not Associated with Measures of Sleep Duration in People of European Ancestry from the Sleep Heart Health Study SO BIOLOGICAL PSYCHIATRY LA English DT Letter ID BODY-MASS INDEX; TWINS; DESIGN C1 [Lane, Jacqueline M.; Tare, Archana; Saxena, Richa] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Lane, Jacqueline M.; Tare, Archana; Saxena, Richa] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Lane, Jacqueline M.; Tare, Archana; Cade, Brian E.; Gottlieb, Daniel J.; Scheer, Frank A. J. L.; Redline, Susan; Saxena, Richa] Harvard Univ, Sch Med, Boston, MA USA. [Lane, Jacqueline M.; Tare, Archana; Saxena, Richa] Broad Inst, Program Med & Populat Genet, Cambridge, England. [Cade, Brian E.; Gottlieb, Daniel J.; Scheer, Frank A. J. L.; Redline, Susan] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. [Chen, Ting-hsu] Boston Univ, Sch Med, Dept Med, Ctr Pulm, Boston, MA 02118 USA. [Chen, Ting-hsu; Gottlieb, Daniel J.] Vet Affairs Boston Healthcare Syst, Boston, MA USA. [Punjabi, Naresh M.] Johns Hopkins Univ, Div Pulm & Crit Med, Baltimore, MD USA. RP Saxena, R (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM saxena@chgr.mgh.harvard.edu RI Scheer, Frank/C-2795-2012 FU NHLBI NIH HHS [U01HL53941, U01 HL053941, U01 HL053937, U01HL 63463, U01 HL053916, U01HL53934, U01 HL063429, U01 HL053934, U01HL 53937, U01HL63429, U01HL53916, U01 HL063463]; NIDDK NIH HHS [R21 DK089378] NR 23 TC 2 Z9 2 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 2013 VL 74 IS 12 BP E33 EP E35 DI 10.1016/j.biopsych.2013.06.006 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 252DC UT WOS:000326983900001 PM 23871470 ER PT J AU MacIntyre, CR Heywood, AE Kovoor, P Ridda, I Seale, H Tan, T Gao, ZH Katelaris, AL Siu, HWD Lo, V Lindley, R Dwyer, DE AF MacIntyre, C. Raina Heywood, Anita E. Kovoor, Pramesh Ridda, Iman Seale, Holly Tan, Timothy Gao, Zhanhai Katelaris, Anthea L. Siu, Ho Wai Derrick Lo, Vincent Lindley, Richard Dwyer, Dominic E. TI Ischaemic heart disease, influenza and influenza vaccination: a prospective case control study SO HEART LA English DT Article DE Coronary Artery Disease; Infection ID ACUTE MYOCARDIAL-INFARCTION; ACUTE CORONARY SYNDROMES; FLU VACCINATION; ELDERLY PERSONS; RISK-FACTORS; PREVENTION; INFECTION; ENGLAND; STROKE; WALES AB Background Abundant, indirect epidemiological evidence indicates that influenza contributes to all-cause mortality and cardiovascular hospitalisations with studies showing increases in acute myocardial infarction (AMI) and death during the influenza season. Objective To investigate whether influenza is a significant and unrecognised underlying precipitant of AMI. Design Case-control study. Setting Tertiary referral hospital in Sydney, Australia, during 2008 to 2010. Patients Cases were inpatients with AMI and controls were outpatients without AMI at a hospital in Sydney, Australia. Main outcome measures Primary outcome was laboratory evidence of influenza. Secondary outcome was baseline self-reported acute respiratory tract infection. Results Of 559 participants, 34/275 (12.4%) cases and 19/284 (6.7%) controls had influenza (OR 1.97, 95% CI 1.09 to 3.54); half were vaccinated. None were recognised as having influenza during their clinical encounter. After adjustment, influenza infection was no longer a significant predictor of recent AMI. However, influenza vaccination was significantly protective (OR 0.55, 95% CI 0.35 to 0.85), with a vaccine effectivenessof 45% (95% CI 15% to 65%). Conclusions Recent influenza infection was an unrecognised comorbidity in almost 10% of hospital patients. Influenza did not predict AMI, but vaccination was significantly protective but underused. The potential population health impact of influenza vaccination, particularly in the age group 50-64years, who are at risk for AMI but not targeted for vaccination, should be further explored. Our data should inform vaccination policy and cardiologists should be aware of missed opportunities to vaccinate individuals with ischaemic heart disease against influenza. C1 [MacIntyre, C. Raina; Heywood, Anita E.; Ridda, Iman; Seale, Holly; Gao, Zhanhai] Univ New S Wales, UNSW Med, Sch Publ Hlth & Community Med, Sydney, NSW 2052, Australia. [MacIntyre, C. Raina; Ridda, Iman] Childrens Hosp, NCIRS, Westmead, NSW, Australia. [Kovoor, Pramesh; Tan, Timothy; Lindley, Richard; Dwyer, Dominic E.] Univ Sydney, Westmead Hosp, Sydney Med Sch, Westmead, NSW 2145, Australia. [Tan, Timothy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Katelaris, Anthea L.; Siu, Ho Wai Derrick; Lo, Vincent] Univ New S Wales, Fac Med, Sydney, NSW, Australia. [Dwyer, Dominic E.] Westmead Hosp, Inst Clin Pathol & Microbiol ICPMR, Ctr Infect Dis & Microbiol Lab Serv, Sydney, NSW, Australia. RP Heywood, AE (reprint author), Univ New S Wales, UNSW Med, Sch Publ Hlth & Community Med, Level 2,Samuels Bldg, Sydney, NSW 2052, Australia. EM a.heywood@unsw.edu.au RI Lindley, Richard/B-8148-2013 OI Lindley, Richard/0000-0002-0104-5679 FU GlaxoSmithKline (GSK), Belgium; Australian National Health and Medical Research Council (NHMRC) FX This work was supported by a grant from GlaxoSmithKline (GSK), Belgium. Dr Iman Ridda and Dr Holly Seale are supported by Australian National Health and Medical Research Council (NHMRC) Training Fellowships. NR 33 TC 15 Z9 17 U1 0 U2 19 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 EI 1468-201X J9 HEART JI Heart PD DEC 15 PY 2013 VL 99 IS 24 BP 1843 EP 1848 DI 10.1136/heartjnl-2013-304320 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 255ON UT WOS:000327249800010 PM 23966030 ER PT J AU Augustinack, JC van der Kouwe, AJW Fischl, B AF Augustinack, Jean C. van der Kouwe, Andre J. W. Fischl, Bruce TI Medial Temporal Cortices in Ex Vivo Magnetic Resonance Imaging SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Review DE cortical localization; entorhinal cortex; verrucae; perirhinal cortex; perforant pathway ID HUMAN CEREBRAL-CORTEX; HIGH-RESOLUTION MRI; MILD COGNITIVE IMPAIRMENT; SUPERIOR PARIETAL CORTEX; HUMAN PERIRHINAL CORTEX; ENTORHINAL AREA 28; ALZHEIMERS-DISEASE; IN-VIVO; HUMAN-BRAIN; PARAHIPPOCAMPAL GYRUS AB This review focuses on the ex vivo magnetic resonance imaging (MRI) modeling of medial temporal cortices and associated structures, the entorhinal verrucae and the perforant pathway. Typical in vivo MRI has limited resolution due to constraints on scan times and does not show laminae in the medial temporal lobe. Recent studies using ex vivo MRI have demonstrated lamina in the entorhinal, perirhinal, and hippocampal cortices. These studies have enabled probabilistic brain mapping that is based on the ex vivo MRI contrast, validated to histology, and subsequently mapped onto an in vivo spherically warped surface model. Probabilistic maps are applicable to other in vivo studies. J. Comp. Neurol. 521:4177-4188, 2013. (c) 2013 Wiley Periodicals, Inc. C1 [Augustinack, Jean C.; van der Kouwe, Andre J. W.; Fischl, Bruce] MGH, Dept Radiol, Athinoula A Martinos Ctr, Charlestown, MA 02129 USA. [Fischl, Bruce] MIT, Comp Sci & AI Lab, Cambridge, MA 02139 USA. RP Augustinack, JC (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Bldg 149,13th St, Boston, MA 02129 USA. EM jean@nmr.mgh.harvard.edu FU National Center for Research Resources [P41-RR14075]; NCRR BIRN Morphometric Project [BIRN002, U24 RR021382]; National Institute for Biomedical Imaging and Bioengineering [R01EB006758]; National Institute on Aging [AG28521, AG022381, 5R01AG008122-22]; National Center for Alternative Medicine [RC1 AT005728-01]; National Institute for Neurological Disorders and Stroke [R01 NS052585-01, 1R21NS072652-01, 1R01NS070963]; Shared Instrumentation [1S10RR023401, 1S10RR019307, 1S10RR023043]; Autism & Dyslexia Project; Ellison Medical Foundation; NIH Blueprint for Neuroscience Research part of the multi-institutional Human Connectome Project [5U01-MH093765] FX Grant sponsor: National Center for Research Resources; Grant numbers: P41-RR14075 and the The NCRR BIRN Morphometric Project BIRN002, U24 RR021382; Grant sponsor: National Institute for Biomedical Imaging and Bioengineering; Grant number: R01EB006758; Grant sponsor: National Institute on Aging; Grant numbers: AG28521, AG022381, 5R01AG008122-22; Grant sponsor: National Center for Alternative Medicine; Grant number: RC1 AT005728-01; Grant sponsor: National Institute for Neurological Disorders and Stroke; Grant numbers: R01 NS052585-01, 1R21NS072652-01, 1R01NS070963; Grant sponsor: Resources provided by Shared Instrumentation; Grant numbers: 1S10RR023401, 1S10RR019307, 1S10RR023043; Grant sponsor: Autism & Dyslexia Project funded by the Ellison Medical Foundation; Grant sponsor: NIH Blueprint for Neuroscience Research part of the multi-institutional Human Connectome Project; Grant number: 5U01-MH093765. NR 107 TC 5 Z9 5 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9967 EI 1096-9861 J9 J COMP NEUROL JI J. Comp. Neurol. PD DEC 15 PY 2013 VL 521 IS 18 BP 4177 EP 4188 DI 10.1002/cne.23432 PG 12 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 240RI UT WOS:000326114300008 PM 23881818 ER PT J AU Pooler, AM Polydoro, M Wegmann, SK Pitstick, R Kay, KR Sanchez, L Carlson, GA Gomez-Isla, T Albers, MW Spires-Jones, TL Hyman, BT AF Pooler, Amy M. Polydoro, Manuela Wegmann, Susanne K. Pitstick, Rose Kay, Kevin R. Sanchez, Laura Carlson, George A. Gomez-Isla, Teresa Albers, Mark W. Spires-Jones, Tara L. Hyman, Bradley T. TI Tau-Amyloid Interactions in the rTgTauEC Model of Early Alzheimer's Disease Suggest Amyloid-Induced Disruption of Axonal Projections and Exacerbated Axonal Pathology SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE Van Hoesen; Alzheimer's disease; perforant pathway ID PERFORANT PATHWAY ZONE; ENTORHINAL AREA 28; A-BETA; RHESUS-MONKEY; TRANSGENIC MICE; NEUROFIBRILLARY TANGLES; MOLECULAR EPIDEMIOLOGY; HIPPOCAMPAL-FORMATION; CEREBRAL-CORTEX; DENTATE GYRUS AB Early observations of the patterns of neurofibrillary tangles and amyloid plaques in Alzheimer's disease suggested a hierarchical vulnerability of neurons for tangles, and a widespread nonspecific pattern of plaques that nonetheless seemed to correlate with the terminal zone of tangle-bearing neurons in some instances. The first neurofibrillary cortical lesions in Alzheimer's disease occur in the entorhinal cortex, thereby disrupting the origin of the perforant pathway projection to the hippocampus, and amyloid deposits are often found in the molecular layer of the dentate gyrus, which is the terminal zone of the entorhinal cortex. We modeled these anatomical changes in a transgenic mouse model that overexpresses both P301L tau (uniquely in the medial entorhinal cortex) and mutant APP/PS1 (in a widespread distribution) to examine the anatomical consequences of early tangles, plaques, or the combination. We find that tau uniformly occupies the terminal zone of the perforant pathway in tau-expressing mice. By contrast, the addition of amyloid deposits in this area leads to disruption of the perforant pathway terminal zone and apparent aberrant distribution of tau-containing axons. Moreover, human P301L tau-containing axons appear to increase the extent of dystrophic axons around plaques. Thus, the presence of amyloid deposits in the axonal terminal zone of pathological tau-containing neurons profoundly impacts their normal connectivity. J. Comp. Neurol. 521:4236-4248, 2013. (c) 2013 Wiley Periodicals, Inc. C1 [Pooler, Amy M.] Kings Coll London, Inst Psychiat, Dept Neurosci, London SE5 8AF, England. [Pooler, Amy M.; Polydoro, Manuela; Wegmann, Susanne K.; Kay, Kevin R.; Sanchez, Laura; Gomez-Isla, Teresa; Albers, Mark W.; Spires-Jones, Tara L.; Hyman, Bradley T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. [Pitstick, Rose; Carlson, George A.] McLaughlin Res Inst, Great Falls, MT USA. RP Hyman, BT (reprint author), Mass Gen Inst Neurodegenerat, 114 16th St, Boston, MA 02129 USA. EM bhyman@partners.org FU National Institutes of Health (NIH) [R00AG033670, R01AG026249-07]; American Health Assistance Foundation; Alzheimer's Research UK FX Grant sponsor: National Institutes of Health (NIH); Grant numbers: R00AG033670; R01AG026249-07; Grant sponsor: American Health Assistance Foundation; Grant sponsor: Alzheimer's Research UK. NR 54 TC 5 Z9 5 U1 0 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9967 EI 1096-9861 J9 J COMP NEUROL JI J. Comp. Neurol. PD DEC 15 PY 2013 VL 521 IS 18 BP 4236 EP 4248 DI 10.1002/cne.23411 PG 13 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 240RI UT WOS:000326114300011 PM 23839581 ER PT J AU Perez, SE Raghanti, MA Hof, PR Kramer, L Ikonomovic, MD Lacor, PN Erwin, JM Sherwood, CC Mufson, EJ AF Perez, Sylvia E. Raghanti, Mary Ann Hof, Patrick R. Kramer, Lynn Ikonomovic, Milos D. Lacor, Pascale N. Erwin, Joseph M. Sherwood, Chet C. Mufson, Elliott J. TI Alzheimer's Disease Pathology in the Neocortex and Hippocampus of the Western Lowland Gorilla (Gorilla gorilla gorilla) SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE aging; amyloid; brain; evolution; great ape; mammals; pathology; tau ID CEREBRAL AMYLOID ANGIOPATHY; AGED SQUIRREL-MONKEYS; PROGRESSIVE SUPRANUCLEAR PALSY; MILD COGNITIVE IMPAIRMENT; PAIRED HELICAL FILAMENTS; CENTRAL-NERVOUS-SYSTEM; SENILE PLAQUES; NEUROFIBRILLARY TANGLES; A-BETA; BASAL FOREBRAIN AB The two major histopathologic hallmarks of Alzheimer's disease (AD) are amyloid beta protein (A) plaques and neurofibrillary tangles (NFT). A pathology is a common feature in the aged nonhuman primate brain, whereas NFT are found almost exclusively in humans. Few studies have examined AD-related pathology in great apes, which are the closest phylogenetic relatives of humans. In the present study, we examined A and tau-like lesions in the neocortex and hippocampus of aged male and female western lowland gorillas using immunohistochemistry and histochemistry. Analysis revealed an age-related increase in A-immunoreactive plaques and vasculature in the gorilla brain. A plaques were more abundant in the neocortex and hippocampus of females, whereas A-positive blood vessels were more widespread in male gorillas. Plaques were also A40-, A42-, and A oligomer-immunoreactive, but only weakly thioflavine S- or 6-CN-PiB-positive in both sexes, indicative of the less fibrillar (diffuse) nature of A plaques in gorillas. Although phosphorylated neurofilament immunostaining revealed a few dystrophic neurites and neurons, choline acetyltransferase-immunoreactive fibers were not dystrophic. Neurons stained for the tau marker Alz50 were found in the neocortex and hippocampus of gorillas at all ages. Occasional Alz50-, MC1-, and AT8-immunoreactive astrocyte and oligodendrocyte coiled bodies and neuritic clusters were seen in the neocortex and hippocampus of the oldest gorillas. This study demonstrates the spontaneous presence of both A plaques and tau-like lesions in the neocortex and hippocampus in old male and female western lowland gorillas, placing this species at relevance in the context of AD research. J. Comp. Neurol. 521:4318-4338, 2013. (c) 2013 Wiley Periodicals, Inc. C1 [Perez, Sylvia E.; Mufson, Elliott J.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Raghanti, Mary Ann] Kent State Univ, Dept Anthropol, Kent, OH 44242 USA. [Raghanti, Mary Ann] Kent State Univ, Sch Biomed Sci, Kent, OH 44242 USA. [Raghanti, Mary Ann] Cleveland Metroparks Zoo, Cleveland, OH 44109 USA. [Hof, Patrick R.] Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, New York, NY 10029 USA. [Hof, Patrick R.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. [Kramer, Lynn] Dallas Zoo Management, Dallas, TX 75203 USA. [Ikonomovic, Milos D.] Carnegie Mellon Univ, VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15213 USA. [Ikonomovic, Milos D.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. [Ikonomovic, Milos D.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. [Lacor, Pascale N.] Northwestern Univ, Dept Neurobiol, Evanston, IL 60208 USA. [Lacor, Pascale N.] Northwestern Univ, Cognit Neurol & Alzheimers Dis Ctr, Evanston, IL 60208 USA. [Erwin, Joseph M.; Sherwood, Chet C.] George Washington Univ, Dept Anthropol, Washington, DC 20052 USA. RP Mufson, EJ (reprint author), Rush Univ, Med Ctr, Chicago, IL 60612 USA. EM emufson@rush.edu FU National Science Foundation [BCS-0921079, BCS-0827531]; James S. McDonnell Foundation [22002078, 22002029]; National Institute of Aging [AG14308] FX Grant sponsor: National Science Foundation; Grant numbers: BCS-0921079 (to M. A. R.) and BCS-0827531 (to C. C. S.); Grant sponsor: James S. McDonnell Foundation; Grant numbers: 22002078 (to C. C. S., P. R. H) and 22002029 (to C. C. S.); Grant sponsor: National Institute of Aging; Grant number: AG14308 (to J.M.E.). NR 117 TC 17 Z9 17 U1 0 U2 31 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9967 EI 1096-9861 J9 J COMP NEUROL JI J. Comp. Neurol. PD DEC 15 PY 2013 VL 521 IS 18 BP 4318 EP 4338 DI 10.1002/cne.23428 PG 21 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 240RI UT WOS:000326114300016 PM 23881733 ER PT J AU Takebayashi, S Lei, I Ryba, T Sasaki, T Dileep, V Battaglia, D Gao, XL Fang, P Fan, Y Esteban, MA Tang, J Crabtree, GR Wang, Z Gilbert, DM AF Takebayashi, Shin-ichiro Lei, Ienglam Ryba, Tyrone Sasaki, Takayo Dileep, Vishnu Battaglia, Dana Gao, Xiaolin Fang, Peng Fan, Yong Esteban, Miguel A. Tang, Jiong Crabtree, Gerald R. Wang, Zhong Gilbert, David M. TI Murine esBAF chromatin remodeling complex subunits BAF250a and Brg1 are necessary to maintain and reprogram pluripotency-specific replication timing of select replication domains SO EPIGENETICS & CHROMATIN LA English DT Article DE Replication domains; Replication timing; esBAF complex; Chromosome; Developmental regulation ID EMBRYONIC STEM-CELLS; NEURAL DEVELOPMENT; COMPONENT BAF250A; SELF-RENEWAL; HUMAN GENOME; MOUSE; SWI/SNF; TRANSCRIPTION; GENES; RIF1 AB Background: Cellular differentiation and reprogramming are accompanied by changes in replication timing and 3D organization of large-scale (400 to 800 Kb) chromosomal domains ('replication domains'), but few gene products have been identified whose disruption affects these properties. Results: Here we show that deletion of esBAF chromatin-remodeling complex components BAF250a and Brg1, but not BAF53a, disrupts replication timing at specific replication domains. Also, BAF250a-deficient fibroblasts reprogrammed to a pluripotency-like state failed to reprogram replication timing in many of these same domains. About half of the replication domains affected by Brg1 loss were also affected by BAF250a loss, but a much larger set of domains was affected by BAF250a loss. esBAF binding in the affected replication domains was dependent upon BAF250a but, most affected domains did not contain genes whose transcription was affected by loss of esBAF. Conclusions: Loss of specific esBAF complex subunits alters replication timing of select replication domains in pluripotent cells. C1 [Takebayashi, Shin-ichiro; Ryba, Tyrone; Sasaki, Takayo; Dileep, Vishnu; Battaglia, Dana; Gilbert, David M.] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA. [Lei, Ienglam; Gao, Xiaolin; Fang, Peng; Fan, Yong; Wang, Zhong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Richard Simches Res Ctr,Cardiovasc Res Ctr, Boston, MA USA. [Lei, Ienglam; Gao, Xiaolin; Fang, Peng; Fan, Yong; Wang, Zhong] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Lei, Ienglam; Wang, Zhong] Univ Michigan, Sch Med, Cardiovasc Res Ctr, Dept Cardiac Surg, Ann Arbor, MI 48109 USA. [Esteban, Miguel A.] Chinese Acad Sci, Guangzhou Inst Biomed, South China Inst Stem Cell Biol & Regenerat Med, Stem Cell & Canc Biol Grp,Key Lab Regenerat Biol, Guangzhou 510530, Guangdong, Peoples R China. [Esteban, Miguel A.] Chinese Acad Sci, Guangzhou Inst Hlth, South China Inst Stem Cell Biol & Regenerat Med, Stem Cell & Canc Biol Grp,Key Lab Regenerat Biol, Guangzhou 510530, Guangdong, Peoples R China. [Tang, Jiong; Crabtree, Gerald R.] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA. RP Gilbert, DM (reprint author), Florida State Univ, Dept Biol Sci, 319 Stadium Dr, Tallahassee, FL 32306 USA. EM gilbert@bio.fsu.edu FU NIH [GM085354, HL109054]; American Heart Association Predoctoral Fellowship [13PRE17060020]; Harvard Stem Cell Institute; Uehara Memorial Foundation FX We thank Ruth Didier for sorting BrdU-labeled cells and Ichiro Hiratani for advice on the data analyses. This work was supported by NIH grant GM085354 (D.M.G.), American Heart Association Predoctoral Fellowship award 13PRE17060020 (V.D.), a Seed Grant from Harvard Stem Cell Institute (Z.W.), NIH Grant HL109054 (Z.W.), and a post-doctoral fellowship from the Uehara Memorial Foundation (S.T.). NR 43 TC 5 Z9 5 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-8935 J9 EPIGENET CHROMATIN JI Epigenetics Chromatin PD DEC 13 PY 2013 VL 6 AR 42 DI 10.1186/1756-8935-6-42 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 294TW UT WOS:000330071200001 PM 24330833 ER PT J AU Wu, XW Qi, J Bradner, JE Xiao, GT Chen, LF AF Wu, Xuewei Qi, Jun Bradner, James E. Xiao, Gutian Chen, Lin-Feng TI Bromodomain and Extraterminal (BET) Protein Inhibition Suppresses Human T Cell Leukemia Virus 1 (HTLV-1) Tax Protein-mediated Tumorigenesis by Inhibiting Nuclear Factor kappa B (NF-kappa B) Signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Cancer; Leukemia; NF-B; Signaling; Transcription; Brd4; HTLV-1; JQ1; TAX; Acetylation ID LYMPHOTROPIC VIRUS; GENE-EXPRESSION; RAT FIBROBLASTS; DOWN-REGULATION; C-MYC; TRANSFORMATION; ACETYLATION; ACTIVATION; BRD4; LEUKEMIA/LYMPHOMA AB Background: The HTLV-1 oncoprotein Tax induces sustained NF-B activation for cell survival and proliferation gene expression. Results: Recruitment of Brd4 to acetylated RelA is essential for Tax-mediated NF-B target gene expression and cell proliferation. Conclusion: Blocking the binding of Brd4 to acetylated RelA by JQ1 suppresses Tax-mediated NF-B activation and tumorigenesis. Significance: Inhibiting Brd4 could be a potential therapeutic strategy for diseases associated with HTLV-1 infection. The etiology of human T cell leukemia virus 1 (HTLV-1)-mediated adult T cell leukemia is associated with the ability of viral oncoprotein Tax to induce sustained NF-B activation and the expression of many NF-B target genes. Acetylation of the RelA subunit of NF-B and the subsequent recruitment of bromodomain-containing factor Brd4 are important for the expression of NF-B target genes in response to various stimuli. However, their contributions to Tax-mediated NF-B target gene expression and tumorigenesis remain unclear. Here we report that Tax induced the acetylation of lysine 310 of RelA and the binding of Brd4 to acetylated RelA to facilitate Tax-mediated transcriptional activation of NF-B. Depletion of Brd4 down-regulated Tax-mediated NF-B target gene expression and cell proliferation. Inhibiting the interaction of Brd4 and acetylated RelA with the bromodomain extraterminal protein inhibitor JQ1 suppressed the proliferation of Tax-expressing rat fibroblasts and Tax-positive HTLV-1-infected cells and Tax-mediated cell transformation and tumorigenesis. Moreover, JQ1 attenuated the Tax-mediated transcriptional activation of NF-B, triggering the polyubiquitination and proteasome-mediated degradation of constitutively active nuclear RelA. Our results identify Brd4 as a key regulator for Tax-mediated NF-B gene expression and suggest that targeting epigenetic regulators such as Brd4 with the bromodomain extraterminal protein inhibitor might be a potential therapeutic strategy for cancers and other diseases associated with HTLV-1 infection. C1 [Wu, Xuewei; Chen, Lin-Feng] Univ Illinois, Dept Biochem, Urbana, IL 61801 USA. [Chen, Lin-Feng] Univ Illinois, Coll Med, Urbana, IL 61801 USA. [Qi, Jun; Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Xiao, Gutian] Univ Pittsburgh, Med Ctr, Inst Canc, Pittsburgh, PA 15213 USA. RP Chen, LF (reprint author), Univ Illinois, Coll Med, Dept Biochem, MC 714, Urbana, IL 61801 USA. EM lfchen@life.illinois.edu FU National Institutes of Health [DK-085158, DK-093865, CA116616]; University of Illinois at Urbana-Champaign FX This work is supported, in whole or in part, by National Institutes of Health Grants DK-085158, DK-093865 (to L. F. C.), and CA116616 (to G. T. X.). This work was also supported by funds provided by the University of Illinois at Urbana-Champaign (to L. F. C.). NR 53 TC 13 Z9 13 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 13 PY 2013 VL 288 IS 50 BP 36094 EP 36105 DI 10.1074/jbc.M113.485029 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 291FZ UT WOS:000329814700044 PM 24189064 ER PT J AU Manchikanti, L Falco, FJE Diwan, S Hirsch, JA Smith, HS AF Manchikanti, Laxmaiah Falco, Frank J. E. Diwan, Sudhir Hirsch, Joshua A. Smith, Howard S. TI Cervical Radicular Pain: The Role of Interlaminar and Transforaminal Epidural Injections SO CURRENT PAIN AND HEADACHE REPORTS LA English DT Review DE Cervical radicular pain; Cervical interlaminar epidural injections; Cervical transforaminal epidural injections; Particulate steroids; Local anesthetic ID NERVE ROOT BLOCK; MANAGING CHRONIC PAIN; ACTIVE CONTROL TRIAL; SPINAL-CORD DAMAGE; STEROID INJECTIONS; MEDICARE POPULATION; INTERVERTEBRAL FORAMINA; NONSURGICAL TREATMENT; LIGAMENTUM-FLAVUM; DOUBLE-BLIND AB Chronic neck pain and cervical radicular pain are relatively common in the adult population. Treatment for chronic radicular pain recalcitrant to conservative management includes surgical management as well as interventional techniques with epidural injections utilizing either an interlaminar approach or transforaminal approach. Although there have been multiple systematic reviews and randomized clinical trials of cervical interlaminar epidural injections, the literature is sparse in reference to cervical transforaminal epidural injections. Overall, there is good evidence for the effectiveness of cervical interlaminar epidural injections in managing cervical disc herniation and fair evidence in managing central spinal stenosis and postsurgery syndrome. The evidence is poor, however, for cervical transforaminal epidural injections. Complications with cervical interlaminar epidural injections are rare, but more commonly occur with transforaminal epidural injections and can be fatal. Emerging concepts in pain include further randomized trials; proper placebo design; focus on control design (either active control or placebo control); and appropriate methodologic quality assessment and evidence synthesis. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY 42003 USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Falco, Frank J. E.] Mid Atlantic Spine & Pain Phys, Newark, DE USA. [Falco, Frank J. E.] Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. [Diwan, Sudhir] Manhattan Spine & Pain Med, New York, NY USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. [Smith, Howard S.] Albany Med Coll, Albany, NY 12208 USA. RP Manchikanti, L (reprint author), Pain Management Ctr Paducah, 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 120 TC 14 Z9 16 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1531-3433 EI 1534-3081 J9 CURR PAIN HEADACHE R JI Curr. Pain Headache Rep. PD DEC 13 PY 2013 VL 18 IS 1 AR 389 DI 10.1007/s11916-013-0389-9 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA 290MB UT WOS:000329760900001 PM 24338702 ER PT J AU Ciaranello, AL Morris, BL Walensky, RP Weinstein, MC Ayaya, S Doherty, K Leroy, V Hou, TG Desmonde, S Lu, ZG Noubary, F Patel, K Ramirez-Avila, L Losina, E Seage, GR Freedberg, KA AF Ciaranello, Andrea L. Morris, Bethany L. Walensky, Rochelle P. Weinstein, Milton C. Ayaya, Samuel Doherty, Kathleen Leroy, Valeriane Hou, Taige Desmonde, Sophie Lu, Zhigang Noubary, Farzad Patel, Kunjal Ramirez-Avila, Lynn Losina, Elena Seage, George R., III Freedberg, Kenneth A. TI Validation and Calibration of a Computer Simulation Model of Pediatric HIV Infection SO PLOS ONE LA English DT Article ID RESOURCE-LIMITED SETTINGS; TO-CHILD TRANSMISSION; COST-EFFECTIVENESS ANALYSIS; ANTIRETROVIRAL THERAPY; COTE-DIVOIRE; COTRIMOXAZOLE PROPHYLAXIS; DISEASE PROGRESSION; ECONOMIC-EVALUATION; AFRICAN INFANTS; VIRUS-INFECTION AB Background: Computer simulation models can project long-term patient outcomes and inform health policy. We internally validated and then calibrated a model of HIV disease in children before initiation of antiretroviral therapy to provide a framework against which to compare the impact of pediatric HIV treatment strategies. Methods: We developed a patient-level (Monte Carlo) model of HIV progression among untreated children <5 years of age, using the Cost-Effectiveness of Preventing AIDS Complications model framework: the CEPAC-Pediatric model. We populated the model with data on opportunistic infection and mortality risks from the International Epidemiologic Database to Evaluate AIDS (IeDEA), with mean CD4% at birth (42%) and mean CD4% decline (1.4%/month) from the Women and Infants' Transmission Study (WITS). We internally validated the model by varying WITS-derived CD4% data, comparing the corresponding model-generated survival curves to empirical survival curves from IeDEA, and identifying best-fitting parameter sets as those with a root-mean square error (RMSE) <0.01. We then calibrated the model to other African settings by systematically varying immunologic and HIV mortality-related input parameters. Model-generated survival curves for children aged 0-60 months were compared, again using RMSE, to UNAIDS data from >1,300 untreated, HIV-infected African children. Results: In internal validation analyses, model-generated survival curves fit IeDEA data well; modeled and observed survival at 16 months of age were 91.2% and 91.1%, respectively. RMSE varied widely with variations in CD4% parameters; the best fitting parameter set (RMSE = 0.00423) resulted when CD4% was 45% at birth and declined by 6%/month (ages 0-3 months) and 0.3%/month (ages > 3 months). In calibration analyses, increases in IeDEA-derived mortality risks were necessary to fit UNAIDS survival data. Conclusions: The CEPAC-Pediatric model performed well in internal validation analyses. Increases in modeled mortality risks required to match UNAIDS data highlight the importance of pre-enrollment mortality in many pediatric cohort studies. C1 [Ciaranello, Andrea L.; Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Morris, Bethany L.; Walensky, Rochelle P.; Doherty, Kathleen; Hou, Taige; Lu, Zhigang; Noubary, Farzad; Losina, Elena; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Ciaranello, Andrea L.; Walensky, Rochelle P.; Ramirez-Avila, Lynn; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Ciaranello, Andrea L.; Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Losina, Elena] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Walensky, Rochelle P.; Losina, Elena; Freedberg, Kenneth A.] Harvard Univ, Ctr AIDS Res, Boston, MA 02115 USA. [Weinstein, Milton C.; Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Patel, Kunjal; Seage, George R., III] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Ayaya, Samuel] Moi Univ, Dept Child Hlth & Pediat, Eldoret, Kenya. [Leroy, Valeriane; Desmonde, Sophie] Univ Bordeaux 2, Inst Sante Publ & Dev, INSERM, U897, F-33076 Bordeaux, France. [Ramirez-Avila, Lynn] Childrens Hosp, Boston, MA 02115 USA. [Ramirez-Avila, Lynn] Univ Calif Los Angeles, Dept Pediat, Div Pediat Infect Dis, Los Angeles, CA 90024 USA. [Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Ciaranello, AL (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM aciaranello@partners.org RI Leroy, Valeriane/F-8129-2013 OI Leroy, Valeriane/0000-0003-3542-8616 FU National Institutes of Health (International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT); National Institute of Allergy and Infectious Diseases [K01 AI078754, K24 AI062476, R01 AI058736, R01 AI093269, U01 AI069911, U01AI09919]; Harvard Center for AIDS Research; Elizabeth Glaser Pediatric AIDS Foundation; March of Dimes Foundation; Massachusetts General Hospital Executive Committee on Research; National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI068632]; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Mental Health (NIMH) [AI068632]; Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases [5 U01 AI41110, 1 U01 AI068616]; National Institute of Allergy and Infectious Diseases (NIAID); NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network; NICHD [N01-DK-9-001/HHSN267200800001C] FX This work was supported by the National Institutes of Health (International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT); National Institute of Allergy and Infectious Diseases, through K01 AI078754, K24 AI062476, R01 AI058736, R01 AI093269 (RPW), U01 AI069911, U01AI09919 (IeDEA West Africa); the Harvard Center for AIDS Research); the Elizabeth Glaser Pediatric AIDS Foundation, the March of Dimes Foundation, and the Massachusetts General Hospital Executive Committee on Research. Overall support for IMPAACT was provided by the National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI068632], the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Mental Health (NIMH) [AI068632]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This work was supported by the Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases cooperative agreement #5 U01 AI41110 with the Pediatric AIDS Clinical Trials Group (PACTG) and #1 U01 AI068616 with the IMPAACT Group. Support of the sites was provided by the National Institute of Allergy and Infectious Diseases (NIAID) and the NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network funded by NICHD (contract number N01-DK-9-001/HHSN267200800001C). Sophie Desmonde is a fellow of the Ecole des Hautes Etudes en Sante Publique (EHESP), Rennes, France. The funders had no role in study design, data analysis, interpretation of results, or decision to publish. NR 58 TC 3 Z9 3 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 13 PY 2013 VL 8 IS 12 AR UNSP e83389 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 276FP UT WOS:000328734200082 PM 24349503 ER PT J AU Liu, Y Yang, XS Utheim, TP Guo, CY Xiao, MC Liu, Y Yin, ZQ Ma, J AF Liu, Yong Yang, Xuesen Utheim, Tor Paaaske Guo, Chenying Xiao, Mingchun Liu, Yan Yin, Zhengqin Ma, Jie TI Correlation of Cytokine Levels and Microglial Cell Infiltration during Retinal Degeneration in RCS Rats SO PLOS ONE LA English DT Article ID POSTNATAL-DEVELOPMENT; NERVOUS-SYSTEM; DYSTROPHY; PHAGOCYTOSIS; MIGRATION; LIGHT; INFLAMMATION; ACTIVATION; DETACHMENT; RECEPTORS AB Microglial cells, which are immunocompetent cells, are involved in all diseases of the central nervous system. During their activation in various diseases, a variety of soluble factors are released. In the present study, the correlation between cytokine levels and microglial cell migration in the course of retinal degeneration of Royal College of Surgeons (RCS) rats was evaluated. MFG-E8 and CD11b were used to confirm the microglial cells. In the retina of RCS rats, the mRNA expression of seven genes (MFG-E8 and its integrins alpha upsilon and beta 5, CD11b and the cytokines TNF-alpha, IL-1 beta, and MCP-1) formed almost similar bimodal peak distributions, which were centred at P7 and P45 to P60. In contrast, in rdy rats, which comprised the control group, a unimodal peak distribution centred at P14 was observed. The gene expression accompanied the activation and migration of microglial cells from the inner to the outer layer of the retina during the process of degeneration. Principal component analysis and discriminant function analysis revealed that the expression of these seven genes, especially TNF-alpha and CD11b, positively correlated with retinal degeneration and microglial activity during retinal degeneration in RCS rats, but not in the control rats. Furthermore, linear regression analysis demonstrated a significant correlation between the expression of these genes and the activation of microglial cells in the dystrophic retina. Our findings suggest that the suppression of microglial cells and the blockade of their cytotoxic effects may constitute a novel therapeutic strategy for treating photoreceptor death in various retinal disorders. C1 [Liu, Yong; Yin, Zhengqin] Third Mil Med Univ, Key Lab Visual Damage & Repair Chongqing, Southwest Eye Hosp, Southwest Hosp, Chongqing, Peoples R China. [Yang, Xuesen; Liu, Yan] Third Mil Med Univ, Inst Trop Med, Chongqing, Peoples R China. [Utheim, Tor Paaaske; Guo, Chenying; Ma, Jie] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA USA. [Utheim, Tor Paaaske] Oslo Univ Hosp, Dept Med Biochem, Oslo, Norway. [Xiao, Mingchun] Southwest Univ, Coll Life Sci, Chongqing, Peoples R China. RP Liu, Y (reprint author), Third Mil Med Univ, Key Lab Visual Damage & Repair Chongqing, Southwest Eye Hosp, Southwest Hosp, Chongqing, Peoples R China. EM liu_yong2012@yahoo.com FU National Basic Research Program of China (973 Program) [2013CB967002]; National Natural Science Foundation of China [81130017, 30700931, 30970672] FX This study was supported by the the National Basic Research Program of China (973 Program, 2013CB967002) and National Natural Science Foundation of China (numbers 81130017, 30700931 and 30970672). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 38 TC 7 Z9 7 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 13 PY 2013 VL 8 IS 12 AR e82061 DI 10.1371/journal.pone.0082061 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 276FP UT WOS:000328734200023 PM 24349184 ER PT J AU Sitek, KR Mathalon, DH Roach, BJ Houde, JF Niziolek, CA Ford, JM AF Sitek, Kevin R. Mathalon, Daniel H. Roach, Brian J. Houde, John F. Niziolek, Caroline A. Ford, Judith M. TI Auditory Cortex Processes Variation in Our Own Speech SO PLOS ONE LA English DT Article ID EVENT-RELATED POTENTIALS; COROLLARY DISCHARGE DYSFUNCTION; FEEDBACK-CONTROL; SENSORIMOTOR ADAPTATION; EVOKED-POTENTIALS; VOICE; PITCH; SCHIZOPHRENIA; RESPONSES; MANIPULATION AB As we talk, we unconsciously adjust our speech to ensure it sounds the way we intend it to sound. However, because speech production involves complex motor planning and execution, no two utterances of the same sound will be exactly the same. Here, we show that auditory cortex is sensitive to natural variations in self-produced speech from utterance to utterance. We recorded event-related potentials (ERPs) from ninety-nine subjects while they uttered "ah'' and while they listened to those speech sounds played back. Subjects' utterances were sorted based on their formant deviations from the previous utterance. Typically, the N1 ERP component is suppressed during talking compared to listening. By comparing ERPs to the least and most variable utterances, we found that N1 was less suppressed to utterances that differed greatly from their preceding neighbors. In contrast, an utterance's difference from the median formant values did not affect N1. Trial-to-trial pitch (f0) deviation and pitch difference from the median similarly did not affect N1. We discuss mechanisms that may underlie the change in N1 suppression resulting from trial-to-trial formant change. Deviant utterances require additional auditory cortical processing, suggesting that speaking-induced suppression mechanisms are optimally tuned for a specific production. C1 [Sitek, Kevin R.; Mathalon, Daniel H.; Roach, Brian J.; Ford, Judith M.] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA USA. [Mathalon, Daniel H.; Niziolek, Caroline A.; Ford, Judith M.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Houde, John F.; Niziolek, Caroline A.] Univ Calif San Francisco, Dept Otolaryngol, San Francisco, CA 94143 USA. RP Sitek, KR (reprint author), Harvard Univ, Program Speech & Hearing Biosci & Technol, Div Med Sci, Boston, MA 02115 USA. EM sitek@fas.harvard.edu OI Roach, Brian/0000-0002-3264-1465; Niziolek, Caroline/0000-0002-6085-1371 FU University of California, San Francisco's Resource Allocation Program; Department of Veterans Affairs; National Institute of Mental Health [MH-58262, MH-076989]; National Institute on Deafness and Other Communication Disorders [R01-DC010145]; National Science Foundation [BCS-0926196]; National Institutes of Health [NRSA 1F32DC011249]; National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI [UL1 TR000004] FX This work was supported by a grant from the University of California, San Francisco's Resource Allocation Program, the Department of Veterans Affairs (Merit Review, Research Career Scientist: JF), the National Institute of Mental Health (MH-58262: JF, BR, DM, KS; MH-076989: JF, BR, DM, KS), the National Institute on Deafness and Other Communication Disorders (R01-DC010145: JH, CN), the National Science Foundation (BCS-0926196: JH, CN), the National Institutes of Health (NRSA 1F32DC011249: CN), and the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant Number UL1 TR000004 (JF, DM). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 51 TC 9 Z9 9 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 13 PY 2013 VL 8 IS 12 AR e82925 DI 10.1371/journal.pone.0082925 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 276FP UT WOS:000328734200060 PM 24349399 ER PT J AU Wang, MP Wang, X Lam, TH Viswanath, K Chan, SS AF Wang, Man Ping Wang, Xin Lam, Tai Hing Viswanath, Kasisomayajula Chan, Sophia S. TI Health Information Seeking Partially Mediated the Association between Socioeconomic Status and Self-Rated Health among Hong Kong Chinese SO PLOS ONE LA English DT Article ID COMMUNICATION; INEQUALITIES; DISPARITIES; BEHAVIORS; MORTALITY; RISK AB Background: Poor self-rated health (SRH) is socially patterned with health communication inequalities, arguably, serving as one mechanisms. This study investigated the effects of health information seeking on SRH, and its mediation effects on disparities in SRH. Methods: We conducted probability-based telephone surveys administered over telephone in 2009, 2010/11 and 2012 to monitor health information use among 4553 Chinese adults in Hong Kong. Frequency of information seeking from television, radio, newspapers/magazines and Internet was dichotomised as < 1 time/month and >= 1 time/month. Adjusted odds ratios (aOR) for poor SRH were calculated for health information seeking from different sources and socioeconomic status (education and income). Mediation effects of health information seeking on the association between SES and poor SRH was estimated. Results: Poor SRH was associated with lower socioeconomic status (P for trend < 0.001), and less than monthly health information seeking from newspapers/magazines (aOR = 1.23, 95% CI 1.07-1.42) and Internet (aOR = 1.13, 95% CI 0.98-1.31). Increasing combined frequency of health information seeking from newspapers/magazines and Internet was linearly associated with better SRH (P for trend < 0.01). Health information seeking from these two sources contributed 9.2% and 7.9% of the total mediation effects of education and household income on poor SRH, respectively. Conclusions: Poor SRH was associated with lower socioeconomic status, and infrequent health information seeking from newspapers/magazines and Internet among Hong Kong Chinese. Disparities in SRH may be partially mediated by health information seeking from newspapers/magazines and Internet. C1 [Wang, Man Ping; Wang, Xin; Lam, Tai Hing] Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China. [Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Ctr Community Based Res,Dept Social & Behav Sci, Boston, MA 02115 USA. [Chan, Sophia S.] Univ Hong Kong, Sch Nursing, Hong Kong, Hong Kong, Peoples R China. RP Lam, TH (reprint author), Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China. EM hrmrlth@hku.hk FU Hong Kong Jockey Club Charities Trust FX This study was a part of the project "FAMILY: A Jockey Club Initiative for a Harmonious Society,'' which was funded by The Hong Kong Jockey Club Charities Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 35 TC 3 Z9 3 U1 1 U2 14 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 13 PY 2013 VL 8 IS 12 AR e82720 DI 10.1371/journal.pone.0082720 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 276FP UT WOS:000328734200052 PM 24349347 ER PT J AU Sancak, Y Markhard, AL Kitami, T Kovacs-Bogdan, E Kamer, KJ Udeshi, ND Carr, SA Chaudhuri, D Clapham, DE Li, AA Calvo, SE Goldberger, O Mootha, VK AF Sancak, Yasemin Markhard, Andrew L. Kitami, Toshimori Kovacs-Bogdan, Erika Kamer, Kimberli J. Udeshi, Namrata D. Carr, Steven A. Chaudhuri, Dipayan Clapham, David E. Li, Andrew A. Calvo, Sarah E. Goldberger, Olga Mootha, Vamsi K. TI EMRE Is an Essential Component of the Mitochondrial Calcium Uniporter Complex SO SCIENCE LA English DT Article ID CA2+ UPTAKE; PROTEIN; MICU1; MCU AB The mitochondrial uniporter is a highly selective calcium channel in the organelle's inner membrane. Its molecular components include the EF-hand-containing calcium-binding proteins mitochondrial calcium uptake 1 (MICU1) and MICU2 and the pore-forming subunit mitochondrial calcium uniporter (MCU). We sought to achieve a full molecular characterization of the uniporter holocomplex (uniplex). Quantitative mass spectrometry of affinity-purified uniplex recovered MICU1 and MICU2, MCU and its paralog MCUb, and essential MCU regulator (EMRE), a previously uncharacterized protein. EMRE is a 10-kilodalton, metazoan-specific protein with a single transmembrane domain. In its absence, uniporter channel activity was lost despite intact MCU expression and oligomerization. EMRE was required for the interaction of MCU with MICU1 and MICU2. Hence, EMRE is essential for in vivo uniporter current and additionally bridges the calcium-sensing role of MICU1 and MICU2 with the calcium-conducting role of MCU. C1 [Sancak, Yasemin; Markhard, Andrew L.; Kitami, Toshimori; Kovacs-Bogdan, Erika; Kamer, Kimberli J.; Li, Andrew A.; Calvo, Sarah E.; Goldberger, Olga; Mootha, Vamsi K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol,Dept Syst Biol, Boston, MA 02115 USA. [Sancak, Yasemin; Kitami, Toshimori; Udeshi, Namrata D.; Carr, Steven A.; Calvo, Sarah E.; Mootha, Vamsi K.] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA USA. [Chaudhuri, Dipayan; Clapham, David E.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Cardiol,Childrens Hosp, Boston, MA 02115 USA. [Chaudhuri, Dipayan; Clapham, David E.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Chaudhuri, Dipayan] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Mootha, VK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol,Dept Syst Biol, Boston, MA 02115 USA. EM vamsi@hms.harvard.edu FU Helen Hay Whitney Foundation; NIH [F32HL107021, DK080261] FX We thank Z. Grabarek and D. M. Shechner for helpful discussions. Y.S. received support from the Helen Hay Whitney Foundation. D. C. received support from NIH F32HL107021. D. E. C. is an Investigator of the Howard Hughes Medical Institute. This work was supported by grants to V. K. M from NIH DK080261 and a gift from W. Dan and Pat Wright. NR 20 TC 124 Z9 131 U1 6 U2 38 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD DEC 13 PY 2013 VL 342 IS 6164 BP 1379 EP 1382 DI 10.1126/science.1242993 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 268UL UT WOS:000328196000053 PM 24231807 ER PT J AU Valentim, CLL Cioli, D Chevalier, FD Cao, XH Taylor, AB Holloway, SP Pica-Mattoccia, L Guidi, A Basso, A Tsai, IJ Berriman, M Carvalho-Queiroz, C Almeida, M Aguilar, H Frantz, DE Hart, PJ LoVerde, PT Anderson, TJC AF Valentim, Claudia L. L. Cioli, Donato Chevalier, Frederic D. Cao, Xiaohang Taylor, Alexander B. Holloway, Stephen P. Pica-Mattoccia, Livia Guidi, Alessandra Basso, Annalisa Tsai, Isheng J. Berriman, Matthew Carvalho-Queiroz, Claudia Almeida, Marcio Aguilar, Hector Frantz, Doug E. Hart, P. John LoVerde, Philip T. Anderson, Timothy J. C. TI Genetic and Molecular Basis of Drug Resistance and Species-Specific Drug Action in Schistosome Parasites SO SCIENCE LA English DT Article ID HYCANTHONE RESISTANCE; PLASMODIUM-FALCIPARUM; MANSONI; OXAMNIQUINE; SULFOTRANSFERASE; MECHANISMS; LINKAGE; GENOME AB Oxamniquine resistance evolved in the human blood fluke (Schistosoma mansoni) in Brazil in the 1970s. We crossed parental parasites differing similar to 500-fold in drug response, determined drug sensitivity and marker segregation in clonally derived second-generation progeny, and identified a single quantitative trait locus (logarithm of odds = 31) on chromosome 6. A sulfotransferase was identified as the causative gene by using RNA interference knockdown and biochemical complementation assays, and we subsequently demonstrated independent origins of loss-of-function mutations in field-derived and laboratory-selected resistant parasites. These results demonstrate the utility of linkage mapping in a human helminth parasite, while crystallographic analyses of protein-drug interactions illuminate the mode of drug action and provide a framework for rational design of oxamniquine derivatives that kill both S. mansoni and S. haematobium, the two species responsible for >99% of schistosomiasis cases worldwide. C1 [Valentim, Claudia L. L.; Cao, Xiaohang; Taylor, Alexander B.; Holloway, Stephen P.; Carvalho-Queiroz, Claudia; Hart, P. John; LoVerde, Philip T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Valentim, Claudia L. L.; Cao, Xiaohang; Taylor, Alexander B.; Holloway, Stephen P.; Carvalho-Queiroz, Claudia; Hart, P. John; Anderson, Timothy J. C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Valentim, Claudia L. L.; Chevalier, Frederic D.; Almeida, Marcio; Anderson, Timothy J. C.] Texas Biomed Res Inst, San Antonio, TX 78245 USA. [Cioli, Donato; Pica-Mattoccia, Livia; Guidi, Alessandra; Basso, Annalisa] CNR, Inst Cell Biol & Neurobiol, Rome, Italy. [Tsai, Isheng J.; Berriman, Matthew] Wellcome Trust Sanger Inst, Hinxton, England. [Aguilar, Hector; Frantz, Doug E.] Univ Texas San Antonio, Dept Chem, San Antonio, TX 78249 USA. [Hart, P. John] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX 78229 USA. RP Hart, PJ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. EM pjhart@biochem.uthscsa.edu; loverde@uthscsa.edu; tanderso@txbiomedgenetics.org RI CHEVALIER, Frederic/E-6852-2010; Tsai, Isheng/H-6606-2014; OI CHEVALIER, Frederic/0000-0003-2611-8106; Tsai, Isheng Jason/0000-0002-2123-5058 FU NIH [5R21-AI096277, 5R21-AI072704, R01-AI097576]; World Health Organization [HQNTD1206356]; Research Facilities Improvement Program Grant from National Center for Research Resources (NIH) [C06 RR013556]; Wellcome Trust [098051]; Robert A. Welch Foundation [AQ-1399]; NIH-National Institute of Allergy and Infectious Diseases [HHSN272201000005I]; University of Texas Health Science Center, San Antonio, Office of the Vice President for Research FX Funded by NIH (5R21-AI096277, 5R21-AI072704, R01-AI097576) and World Health Organization (HQNTD1206356) in facilities constructed with support from Research Facilities Improvement Program Grant (C06 RR013556) from National Center for Research Resources (NIH). Work at Wellcome Trust Sanger Institute was supported by the Wellcome Trust (grant 098051). P.J.H. was funded by the Robert A. Welch Foundation (AQ-1399). B. glabrata snails were supplied by Fred Lewis (Biomedical Research Institute, Rockville, MD) under NIH-National Institute of Allergy and Infectious Diseases contract no. HHSN272201000005I. We thank W. Le Clec'h and C. Valle (capillary sequencing), Z. Lai (RNA sequencing), N. Holroyd (coordinated genome sequencing), Q. Bickle (RNAi support), and G. Anderson (movie compilation). The X-ray Crystallography Core Laboratory is supported by the University of Texas Health Science Center, San Antonio, Office of the Vice President for Research. The authors declare no competing financial interests. Data deposition: Illumina sequence reads (www.ebi.ac.uk/ena/accession#ERP000160); GenBank accessions (KF733459-61), RNAseq data (www.ncbi.nlm.nih.gov/geo/, GSE51847), structural data (www.wwpdb.org/, accession 4MUA, 4MUB) NR 30 TC 30 Z9 31 U1 1 U2 42 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD DEC 13 PY 2013 VL 342 IS 6164 BP 1385 EP 1389 DI 10.1126/science.1243106 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 268UL UT WOS:000328196000055 PM 24263136 ER PT J AU Clark, KB AF Clark, Kevin B. TI Biotic activity of Ca2+-modulating non-traditional antimicrobial and -viral agents SO FRONTIERS IN MICROBIOLOGY LA English DT Editorial Material DE antiifective; bacteria; calcium channel blockers; drug design and development; pathogen toxins; probiotic; protozoa; viruses ID IMMUNODEFICIENCY-VIRUS TYPE-1; POLYAMINE-SENSITIVE-SITE; D-ASPARTATE RECEPTOR; TRYPANOSOMA-CRUZI; X-PROTEIN; ESCHERICHIA-COLI; REQUIRE FUNCTION; MAMMALIAN-CELLS; INFECTED-CELLS; CA2+ C1 [Clark, Kevin B.] Vet Affairs Greater Los Angeles Healthcare Syst, Res & Dev Serv, Los Angeles, CA USA. RP Clark, KB (reprint author), 4229 SE Harney St, Portland, OR USA. EM kbclarkphd@yahoo.com NR 51 TC 3 Z9 3 U1 2 U2 3 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-302X J9 FRONT MICROBIOL JI Front. Microbiol. PD DEC 12 PY 2013 VL 4 AR 381 DI 10.3389/fmicb.2013.00381 PG 4 WC Microbiology SC Microbiology GA AB1KO UT WOS:000331550600001 PM 24376441 ER PT J AU Allen, JD Bluethmann, SM Sheets, M Opdyke, KM Gates-Ferris, K Hurlbert, M Harden, E AF Allen, Jennifer D. Bluethmann, Shirley Morrison Sheets, Margaret Opdyke, Kelly Morrison Gates-Ferris, Kathryn Hurlbert, Marc Harden, Elizabeth TI Women's responses to changes in US preventive task force's mammography screening guidelines: results of focus groups with ethnically diverse women SO BMC PUBLIC HEALTH LA English DT Article DE Mammography; Screening guidelines; Health communication ID SOCIAL NETWORK CHARACTERISTICS; BREAST-CANCER; DECISION AIDS; UNITED-STATES; HEALTH-CARE; RECOMMENDATIONS; SERVICES; ATTITUDES; BENEFITS; IMPACT AB Background: The 2009 U.S. Preventive Services Task Force (USPSTF) changed mammography guidelines to recommend routine biennial screening starting at age 50. This study describes women's awareness of, attitudes toward, and intention to comply with these new guidelines. Methods: Women ages 40-50 years old were recruited from the Boston area to participate in focus groups (k = 8; n = 77). Groups were segmented by race/ethnicity (Caucasian = 39%; African American = 35%; Latina = 26%), audio-taped, and transcribed. Thematic content analysis was used. Results: Participants were largely unaware of the revised guidelines and suspicious that it was a cost-savings measure by insurers and/or providers. Most did not intend to comply with the change, viewing screening as obligatory. Few felt prepared to participate in shared decision-making or advocate for their preferences with respect to screening. Conclusions: Communication about the rationale for mammography guideline changes has left many women unconvinced about potential disadvantages or limitations of screening. Since further guideline changes are likely to occur with advances in technology and science, it is important to help women become informed consumers of health information and active participants in shared decision-making with providers. Additional research is needed to determine the impact of the USPSTF change on women's screening behaviors and on breast cancer outcomes. C1 [Allen, Jennifer D.; Sheets, Margaret; Harden, Elizabeth] Dana Farber Canc Inst, Boston, MA 02215 USA. [Allen, Jennifer D.] Harvard Univ, Sch Med, Boston, MA USA. [Bluethmann, Shirley Morrison] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. [Opdyke, Kelly Morrison; Gates-Ferris, Kathryn] Cicatelli Associates Inc, New York, NY USA. [Hurlbert, Marc] Avon Fdn Women, New York, NY USA. RP Allen, JD (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM jennifer_allen@dfci.harvard.edu RI Allen, Jennifer/M-2113-2015; OI Hurlbert, Marc/0000-0003-3301-3572 FU Avon Foundation for Women/CAI Global; Centers for Disease Control and Prevention [U48DP001946, U48DP001949-02]; Susan G. Komen Foundation [KG111378]; Cancer Education and Career Development Program at the School of Public Health, University of Texas Health Science Center at Houston; National Cancer Institute [R25T 2R25CA57712] FX This work was supported by a grant from the Avon Foundation for Women/CAI Global, and by Cooperative Agreement Numbers U48DP001946 and U48DP001949-02 from the Centers for Disease Control and Prevention. Ms. Bluethmann is supported by the Susan G. Komen Foundation (KG111378) and the Cancer Education and Career Development Program at the School of Public Health, University of Texas Health Science Center at Houston, funded by the National Cancer Institute (R25T 2R25CA57712). The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Susan G. Komen Foundation, the Avon Foundation for Women, CAI Global, the Centers for Disease Control and Prevention or the National Cancer Institute. We also thank the following for their participation, assistance and support: Josh Gagne; Athene Wilson-Glover; Hannah Mills; Dana Mars; Patricia Dolan Mullen; Laura Tom. In addition, we thank the local Avon-funded community organizations, especially local YWCA chapters, without whose assistance the focus groups would not have been possible. NR 72 TC 16 Z9 16 U1 2 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD DEC 12 PY 2013 VL 13 AR 1169 DI 10.1186/1471-2458-13-1169 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AA7MK UT WOS:000331281300001 PM 24330527 ER PT J AU Alt, F Reth, M AF Alt, Frederick Reth, Michael TI Michael Neuberger (1953-2013) Obituary SO IMMUNITY LA English DT Biographical-Item C1 [Alt, Frederick] Harvard Univ, Sch Med, Howard Hughes Med Inst,Dept Genet, Program Cellular & Mol Med,Boston Childrens Hosp, Boston, MA 02115 USA. [Reth, Michael] Univ Freiburg, BIOSS Ctr Biol Signalling Studies, D-79106 Freiburg, Germany. RP Alt, F (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst,Dept Genet, Program Cellular & Mol Med,Boston Childrens Hosp, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu; michael.reth@bioss.uni-freiburg.de FU Howard Hughes Medical Institute NR 0 TC 0 Z9 0 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD DEC 12 PY 2013 VL 39 IS 6 BP 987 EP 988 DI 10.1016/j.immuni.2013.11.004 PG 2 WC Immunology SC Immunology GA AA2UZ UT WOS:000330951000001 PM 24479157 ER PT J AU Lavender, KJ Pang, WW Messer, RJ Duley, AK Race, B Phillips, K Scott, D Peterson, KE Chan, CK Dittmer, U Dudek, T Allen, TM Weissman, IL Hasenkrug, KJ AF Lavender, Kerry J. Pang, Wendy W. Messer, Ronald J. Duley, Amanda K. Race, Brent Phillips, Katie Scott, Dana Peterson, Karin E. Chan, Charles K. Dittmer, Ulf Dudek, Timothy Allen, Todd M. Weissman, Irving L. Hasenkrug, Kim J. TI BLT-humanized C57BL/6 Rag2(-/-)gamma(-/-)(c)CD47(-/-) mice are resistant to GVHD and develop B- and T-cell immunity to HIV infection SO BLOOD LA English DT Article ID HEMATOPOIETIC STEM-CELLS; SCID-HU MOUSE; REGULATORY PROTEIN ALPHA; RECEPTOR-GAMMA CHAIN; IN-VIVO; CORD BLOOD; ENGRAFTMENT; MODEL; IMMUNODEFICIENCY; RESPONSES AB The use of C57BL/6 Rag2(-/-)gamma(-/-)(c) mice as recipients for xenotransplantation with human immune systems (humanization) has been problematic because C57BL/6 SIRP alpha does not recognize human CD47, and such recognition is required to suppress macrophage-mediated phagocytosis of transplanted human hematopoietic stem cells (HSCs). We show that genetic inactivation of CD47 on the C57BL/6 Rag2(-/-)gamma(-/-)(c) background negates the requirement for CD47-signal recognition protein alpha (SIRP alpha) signaling and induces tolerance to transplanted human HSCs. These triple-knockout, bone marrow, liver, thymus (TKO-BLT) humanized mice develop organized lymphoid tissues including mesenteric lymph nodes, splenic follicles and gut-associated lymphoid tissue that demonstrate high levels of multilineage hematopoiesis. Importantly, these mice have an intact complement system and showed no signs of graft-versus-host disease (GVHD) out to 29 weeks after transplantation. Sustained, high-level HIV-1 infection was observed via either intrarectal or intraperitoneal inoculation. TKO-BLT mice exhibited hallmarks of human HIV infection including CD4(+) T-cell depletion, immune activation, and development of HIV-specific B-and T-cell responses. The lack of GVHD makes the TKO-BLT mouse a significantly improved model for long-term studies of pathogenesis, immune responses, therapeutics, and vaccines to human pathogens. C1 [Lavender, Kerry J.; Messer, Ronald J.; Duley, Amanda K.; Race, Brent; Phillips, Katie; Peterson, Karin E.; Hasenkrug, Kim J.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. [Pang, Wendy W.; Chan, Charles K.; Weissman, Irving L.] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA. [Pang, Wendy W.; Chan, Charles K.; Weissman, Irving L.] Stanford Univ, Sch Med, Ludwig Ctr Canc Cell Res, Stanford, CA 94305 USA. [Scott, Dana] NIAID, Rocky Mt Vet Branch, Rocky Mt Labs, NIH, Hamilton, MT USA. [Dittmer, Ulf] Univ Duisburg Essen, Univ Hosp Essen, Inst Virol, Essen, Germany. [Dudek, Timothy; Allen, Todd M.] Ragon Inst Massachusetts Gen Hosp MIT & Harvard, Cambridge, MA USA. RP Hasenkrug, KJ (reprint author), Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59875 USA. EM kerry.lavender@nih.gov; khasenkrug@nih.gov RI Allen, Todd/F-5473-2011 FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health HIVRAD grant [P01 AI104715]; Intramural Research Program of the Medical Faculty of the University Duisburg-Essen; Ludwig Foundation FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health HIVRAD grant P01 AI104715 (to T. M. A.), the Intramural Research Program of the Medical Faculty of the University Duisburg-Essen, and funding from the Ludwig Foundation. NR 38 TC 26 Z9 28 U1 0 U2 6 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 12 PY 2013 VL 122 IS 25 BP 4013 EP 4020 DI 10.1182/blood-2013-06-506949 PG 8 WC Hematology SC Hematology GA 290FH UT WOS:000329739100009 PM 24021673 ER PT J AU Kleiman, LB Krebs, AM Kim, SY Hong, TS Haigis, KM AF Kleiman, Laura B. Krebs, Angela M. Kim, Stephen Y. Hong, Theodore S. Haigis, Kevin M. TI Comparative Analysis of Radiosensitizers for K-RAS Mutant Rectal Cancers SO PLOS ONE LA English DT Article ID CHECKPOINT KINASE 1; DEPENDENT PROTEIN-KINASE; GROWTH-FACTOR RECEPTOR; MITOTIC CATASTROPHE; MEDIATES RADIORESISTANCE; RADIATION-RESISTANCE; GENOMIC INSTABILITY; SELECTIVE INHIBITOR; LOCAL RECURRENCE; CHK1 INHIBITION AB Approximately 40% of rectal cancers harbor activating K-RAS mutations, and these mutations are associated with poor clinical response to chemoradiotherapy. We aimed to identify small molecule inhibitors (SMIs) that synergize with ionizing radiation (IR) ("radiosensitizers") that could be incorporated into current treatment strategies for locally advanced rectal cancers (LARCs) expressing mutant K-RAS. We first optimized a high-throughput assay for measuring individual and combined effects of SMIs and IR that produces similar results to the gold standard colony formation assay. Using this screening platform and K-RAS mutant rectal cancer cell lines, we tested SMIs targeting diverse signaling pathways for radiosensitizing activity and then evaluated our top hits in follow-up experiments. The two most potent radiosensitizers were the Chk1/2 inhibitor AZD7762 and the PI3K/mTOR inhibitor BEZ235. The chemotherapeutic agent 5-fluorouracil (5-FU), which is used to treat LARC, synergized with AZD7762 and enhanced radiosensitization by AZD7762. This study is the first to compare different SMIs in combination with IR for the treatment of K-RAS mutant rectal cancer, and our findings suggest that Chk1/2 inhibitors should be evaluated in new clinical trials for LARC. C1 [Kleiman, Laura B.; Krebs, Angela M.; Kim, Stephen Y.; Haigis, Kevin M.] Massachusetts Gen Hosp, Mol Pathol Unit, Ctr Canc Res, Charlestown, MA 02129 USA. [Kleiman, Laura B.; Krebs, Angela M.; Kim, Stephen Y.; Haigis, Kevin M.] Massachusetts Gen Hosp, Ctr Syst Biol, Charlestown, MA USA. [Krebs, Angela M.] Univ Freiburg, Inst Mol Med & Cell Res, Freiburg, Germany. [Hong, Theodore S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Haigis, KM (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Ctr Canc Res, Charlestown, MA 02129 USA. EM KHAIGIS@PARTNERS.ORG FU American Cancer Society [MGO-114877, PF-11-260-01]; pilot project grant from the Proton Beam Federal Share program FX This work was funded by the American Cancer Society (MGO-114877 to K.M.H. and PF-11-260-01 to L.B.K.) and by a pilot project grant from the Proton Beam Federal Share program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 55 TC 6 Z9 6 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 12 PY 2013 VL 8 IS 12 AR UNSP e82982 DI 10.1371/journal.pone.0082982 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 276EU UT WOS:000328731800086 PM 24349411 ER PT J AU Ray, A Muse, VV Boyer, DF AF Ray, Alaka Muse, Victorine V. Boyer, Daniel F. TI Case 38-2013: A 30-Year-Old Man with Fever and Lymphadenopathy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID KIKUCHI-FUJIMOTO-DISEASE; HISTIOCYTIC NECROTIZING LYMPHADENITIS; FAMILY-PRACTICE; DIAGNOSIS; BIOPSY; MANAGEMENT; CELLS C1 [Ray, Alaka] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Muse, Victorine V.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Boyer, Daniel F.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Ray, Alaka] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Muse, Victorine V.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Boyer, Daniel F.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Ray, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. NR 27 TC 2 Z9 2 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 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 12 PY 2013 VL 369 IS 24 BP 2333 EP 2343 DI 10.1056/NEJMcpc1310002 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 268FV UT WOS:000328156300012 PM 24328468 ER PT J AU Parikh, RB Kirch, RA Smith, TJ Temel, JS AF Parikh, Ravi B. Kirch, Rebecca A. Smith, Thomas J. Temel, Jennifer S. TI Early Specialty Palliative Care-Translating Data in Oncology into Practice SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CELL LUNG-CANCER; RANDOMIZED CONTROLLED-TRIAL; IMPROVE; OPPORTUNITIES; CHEMOTHERAPY; PERCEPTIONS; ACCESS; IMPACT; MODEL; LIFE C1 [Parikh, Ravi B.] Harvard Univ, Sch Med, Boston, MA USA. [Temel, Jennifer S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kirch, Rebecca A.] Amer Canc Soc, Washington, DC USA. [Smith, Thomas J.] Johns Hopkins Univ, Baltimore, MD USA. RP Temel, JS (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA. EM jtemel@partners.org FU NCI NIH HHS [P30 CA006973] NR 33 TC 67 Z9 70 U1 1 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 12 PY 2013 VL 369 IS 24 BP 2347 EP 2351 DI 10.1056/NEJMsb1305469 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 268FV UT WOS:000328156300014 PM 24328469 ER PT J AU Nishihara, R Ogino, S Chan, AT AF Nishihara, Reiko Ogino, Shuji Chan, Andrew T. TI Colorectal-Cancer Incidence and Mortality after Screening REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID LESIONS C1 [Nishihara, Reiko; Ogino, Shuji] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Nishihara, R (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM achan@partners.org NR 4 TC 6 Z9 6 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 12 PY 2013 VL 369 IS 24 BP 2355 EP 2355 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 268FV UT WOS:000328156300019 PM 24350357 ER PT J AU Kashiwagi, S Yuan, JP Forbes, B Hibert, ML Lee, ELQ Whicher, L Goudie, C Yang, Y Chen, T Edelblute, B Collette, B Edington, L Trussler, J Nezivar, J Leblanc, P Bronson, R Tsukada, K Suematsu, M Dover, J Brauns, T Gelfand, J Poznansky, MC AF Kashiwagi, Satoshi Yuan, Jianping Forbes, Benjamin Hibert, Mathew L. Lee, Eugene L. Q. Whicher, Laura Goudie, Calum Yang, Yuan Chen, Tao Edelblute, Beth Collette, Brian Edington, Laurel Trussler, James Nezivar, Jean Leblanc, Pierre Bronson, Roderick Tsukada, Kosuke Suematsu, Makoto Dover, Jeffrey Brauns, Timothy Gelfand, Jeffrey Poznansky, Mark C. TI Near-Infrared Laser Adjuvant for Influenza Vaccine SO PLOS ONE LA English DT Article ID DENDRITIC CELL-MIGRATION; INTRADERMAL VACCINE; MF59-ADJUVANTED INFLUENZA; PROTECTIVE IMMUNITY; VIRUS VACCINE; IN-VIVO; MICE; IMMUNIZATION; MUCOSAL; IMMUNOGENICITY AB Safe and effective immunologic adjuvants are often essential for vaccines. However, the choice of adjuvant for licensed vaccines is limited, especially for those that are administered intradermally. We show that non-tissue damaging, near-infrared (NIR) laser light given in short exposures to small areas of skin, without the use of additional chemical or biological agents, significantly increases immune responses to intradermal influenza vaccination without augmenting IgE. The NIR laser-adjuvanted vaccine confers increased protection in a murine influenza lethal challenge model as compared to unadjuvanted vaccine. We show that NIR laser treatment induces the expression of specific chemokines in the skin resulting in recruitment and activation of dendritic cells and is safe to use in both mice and humans. The NIR laser adjuvant technology provides a novel, safe, low-cost, simple-to-use, potentially broadly applicable and clinically feasible approach to enhancing vaccine efficacy as an alternative to chemical and biological adjuvants. C1 [Kashiwagi, Satoshi; Yuan, Jianping; Forbes, Benjamin; Hibert, Mathew L.; Lee, Eugene L. Q.; Whicher, Laura; Goudie, Calum; Yang, Yuan; Chen, Tao; Edelblute, Beth; Collette, Brian; Edington, Laurel; Trussler, James; Nezivar, Jean; Leblanc, Pierre; Brauns, Timothy; Gelfand, Jeffrey; Poznansky, Mark C.] Massachusetts Gen Hosp, Dept Med, Vaccine & Immunotherapy Ctr, Div Infect Dis, Charlestown, MA 02129 USA. [Bronson, Roderick] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Tsukada, Kosuke] Keio Univ, Fac Sci & Technol, Dept Appl Phys & Physicoinformat, Kohoku Ku, Yokohama, Kanagawa 223, Japan. [Suematsu, Makoto] Keio Univ, Sch Med, Dept Biochem, Shinjuku Ku, Tokyo, Japan. [Dover, Jeffrey] SkinCare Phys Chestnut Hill, Chestnut Hill, MA USA. RP Kashiwagi, S (reprint author), Massachusetts Gen Hosp, Dept Med, Vaccine & Immunotherapy Ctr, Div Infect Dis, Charlestown, MA 02129 USA. EM skashiwagi@partners.org; mpoznansky@partners.org RI Tsukada, Kosuke/C-9986-2014; Suematsu, Makoto/I-8135-2013; OI Suematsu, Makoto/0000-0002-7165-6336; Collette, Brian/0000-0002-9993-8423; Lee, Eugene Li Qun/0000-0003-4725-4959 FU National Institute of Allergy and Infectious Diseases grant [R01AI105131]; Bill & Melinda Gates Foundation (Grand Challenges Explorations) [OPP1046276]; Defense Advanced Research Projects Agency [DARPA-BAA-09-31]; Edmund C. Lynch, Jr. Cancer Research Fund; Friends of VIC FX This work was supported by National Institute of Allergy and Infectious Diseases grant (R01AI105131), the Bill & Melinda Gates Foundation (Grand Challenges Explorations OPP1046276), the Defense Advanced Research Projects Agency (DARPA-BAA-09-31), the Edmund C. Lynch, Jr. Cancer Research Fund and the Friends of VIC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 67 TC 10 Z9 10 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 11 PY 2013 VL 8 IS 12 AR e82899 DI 10.1371/journal.pone.0082899 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 276EG UT WOS:000328730300112 ER PT J AU Weinberger, B Schirmer, M Gothe, RM Siebert, U Fuchs, D Grubeck-Loebenstein, B AF Weinberger, Birgit Schirmer, Michael Gothe, Raffaella Matteucci Siebert, Uwe Fuchs, Dietmar Grubeck-Loebenstein, Beatrix TI Recall Responses to Tetanus and Diphtheria Vaccination Are Frequently Insufficient in Elderly Persons SO PLOS ONE LA English DT Article ID CONJUGATED PNEUMOCOCCAL VACCINE; AGED 60 YEARS; CYTOMEGALOVIRUS-INFECTION; HUMORAL IMMUNITY; OLDER-ADULTS; ASSOCIATION; IMMUNOSENESCENCE; FRAILTY; LIFE; IMMUNOGENICITY AB Demographic changes and a more active life-style in older age have contributed to an increasing public awareness of the need for lifelong vaccination. Currently many older persons have been vaccinated against selected pathogens during childhood but lack regular booster immunizations. The impact of regular vaccinations when started late in life was analyzed in an open, explorative trial by evaluating the immune response against tetanus and diphtheria in healthy older individuals. 252 persons aged above 60 years received a booster vaccination against tetanus, diphtheria, pertussis and polio and a subcohort (n=87) was recruited to receive a second booster vaccination against tetanus, diphtheria and pertussis 5 years later. The percentage of unprotected individuals at the time of enrollment differed substantially for tetanus (12%) and diphtheria (65%). Despite protective antibody concentrations 4 weeks after the first vaccination in almost all vaccinees, antibodies had again dropped below protective levels in 10% (tetanus) and 45% (diphtheria) of the cohort after 5 years. Protection was restored in almost all vaccinees after the second vaccination. No correlation between tetanus-and diphtheria-specific responses was observed, and antibody concentrations were not associated with age-related changes in the T cell repertoire, inflammatory parameters, or CMV-seropositivity suggesting that there was no general biological "non-responder type." Post-vaccination antibody concentrations depended on pre-existing plasma cells and B cell memory as indicated by a strong positive relationship between post-vaccination antibodies and pre-vaccination antibodies as well as antibody-secreting cells. In contrast, antigen-specific T cell responses were not or only weakly associated with antibody concentrations. In conclusion, our findings demonstrate that single shot vaccinations against tetanus and/or diphtheria do not lead to long-lasting immunity in many elderly persons despite administration at relatively short intervals. Sufficient antigen-specific B cell memory B generated by adequate priming and consecutive booster vaccinations and/or exposure is a prerequisite for long-term protection. C1 [Weinberger, Birgit; Grubeck-Loebenstein, Beatrix] Univ Innsbruck, Inst Biomed Aging Res, A-6020 Innsbruck, Austria. [Schirmer, Michael] Med Univ Innsbruck, Dept Internal Med 4, A-6020 Innsbruck, Austria. [Gothe, Raffaella Matteucci; Siebert, Uwe] UMIT Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth & Hlth Technol Assessment, Hall In Tirol, Austria. [Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. [Siebert, Uwe] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Fuchs, Dietmar] Med Univ Innsbruck, Div Biol Chem, Bioctr, A-6020 Innsbruck, Austria. RP Grubeck-Loebenstein, B (reprint author), Univ Innsbruck, Inst Biomed Aging Res, A-6020 Innsbruck, Austria. EM beatrix.grubeck@uibk.ac.at RI Schirmer, Michael/B-1893-2012; OI Schirmer, Michael/0000-0001-9208-7809; Weinberger, Birgit/0000-0002-7084-946X FU Oesterreichische Nationalbank (Anniversery Fund) [13524]; Austrian Green Cross; European Union [280873 ADITEC] FX This work was supported by funds of the Oesterreichische Nationalbank (Anniversery Fund, project number 13524; www.oenb.at/de) and the Austrian Green Cross (www.grueneskreuz.org). The research leading to these results has received funding from the European Union's Seventh Framework Programme [FP7/2007-2013] under Grant Agreement No: 280873 ADITEC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 41 TC 10 Z9 10 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 11 PY 2013 VL 8 IS 12 AR e82967 DI 10.1371/journal.pone.0082967 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 276EG UT WOS:000328730300116 PM 24349407 ER PT J AU Zhi, H Luptak, I Alreja, G Shi, JR Guan, J Metes-Kosik, N Joseph, J AF Zhi, Hui Luptak, Ivan Alreja, Gaurav Shi, Jianru Guan, Jian Metes-Kosik, Nicole Joseph, Jacob TI Effects of Direct Renin Inhibition on Myocardial Fibrosis and Cardiac Fibroblast Function SO PLOS ONE LA English DT Article ID PRESERVED EJECTION FRACTION; MUSCLE-CELL PROLIFERATION; CHRONIC HEART-FAILURE; ANGIOTENSIN-II; HYPERTENSIVE-RATS; INDUCED HYPERHOMOCYSTEINEMIA; ENDOTHELIAL DYSFUNCTION; MESANGIAL CELLS; BLOOD-PRESSURE; HOMOCYSTEINE AB Myocardial fibrosis, a major pathophysiologic substrate of heart failure with preserved ejection fraction (HFPEF), is modulated by multiple pathways including the renin-angiotensin system. Direct renin inhibition is a promising anti-fibrotic therapy since it attenuates the pro-fibrotic effects of renin in addition to that of other effectors of the renin-angiotensin cascade. Here we show that the oral renin inhibitor aliskiren has direct effects on collagen metabolism in cardiac fibroblasts and prevented myocardial collagen deposition in a non-hypertrophic mouse model of myocardial fibrosis. Adult mice were fed hyperhomocysteinemia-inducing diet to induce myocardial fibrosis and treated concomitantly with either vehicle or aliskiren for 12 weeks. Blood pressure and plasma angiotensin II levels were normal in control and hyperhomocysteinemic mice and reduced to levels lower than observed in the control group in the groups treated with aliskiren. Homocysteine-induced myocardial matrix gene expression and fibrosis were also prevented by aliskiren. In vitro studies using adult rat cardiac fibroblasts also showed that aliskiren attenuated the pro-fibrotic pattern of matrix gene and protein expression induced by D, L, homocysteine. Both in vivo and in vitro studies demonstrated that the Akt pathway was activated by homocysteine, and that treatment with aliskiren attenuated Akt activation. In conclusion, aliskiren as mono-therapy has potent and direct effects on myocardial matrix turnover and beneficial effects on diastolic function. C1 [Metes-Kosik, Nicole; Joseph, Jacob] VA Boston Healthcare Syst, West Roxbury, MA USA. [Luptak, Ivan; Alreja, Gaurav; Joseph, Jacob] Boston Univ, Sch Med, Boston, MA 02118 USA. [Zhi, Hui; Shi, Jianru; Guan, Jian; Joseph, Jacob] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Joseph, J (reprint author), VA Boston Healthcare Syst, West Roxbury, MA USA. EM jjoseph16@partners.org OI Luptak, Ivan/0000-0001-7498-7694 FU Novartis Pharmaceuticals FX The work was supported by a resarch grant from Novartis Pharmaceuticals. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 6 Z9 6 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 11 PY 2013 VL 8 IS 12 AR e81612 DI 10.1371/journal.pone.0081612 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 276EG UT WOS:000328730300039 PM 24349097 ER PT J AU Korn, D Carlat, D AF Korn, David Carlat, Daniel TI Conflicts of Interest in Medical Education Recommendations From the Pew Task Force on Medical Conflicts of Interest SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID INDUSTRY C1 [Korn, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Carlat, Daniel] Pew Charitable Trusts, Washington, DC 20004 USA. RP Carlat, D (reprint author), Pew Charitable Trusts, 901 E St NW, Washington, DC 20004 USA. EM dcarlat@pewtrusts.org NR 10 TC 11 Z9 11 U1 1 U2 6 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 11 PY 2013 VL 310 IS 22 BP 2397 EP 2398 DI 10.1001/jama.2013.280889 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 266NN UT WOS:000328030900016 PM 24327035 ER PT J AU Najavits, LM AF Najavits, Lisa M. TI Therapy for Posttraumatic Stress and Alcohol Dependence SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID RANDOMIZED CONTROLLED-TRIAL; SUBSTANCE USE DISORDER; PTSD C1 VA Boston Healthcare Syst, Boston, MA 02130 USA. RP Najavits, LM (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave, Boston, MA 02130 USA. EM lisa.najavits@va.gov NR 5 TC 3 Z9 3 U1 1 U2 8 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 11 PY 2013 VL 310 IS 22 BP 2457 EP 2458 DI 10.1001/jama.2013.282141 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 266NN UT WOS:000328030900030 PM 24327041 ER PT J AU Gale, EM Zhu, J Caravan, P AF Gale, Eric M. Zhu, Jiang Caravan, Peter TI Direct Measurement of the Mn(II) Hydration State in Metal Complexes and Metalloproteins through O-17 NMR Line Widths SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID MRI CONTRAST AGENT; MANGANESE SUPEROXIDE-DISMUTASE; HUMAN SERUM-ALBUMIN; NEPHROGENIC SYSTEMIC FIBROSIS; ELECTRON-SPIN RELAXATION; SPHERE WATER-MOLECULES; MAGNETIC-RESONANCE; X-RAY; LANTHANIDE(III) COMPLEXES; AQUEOUS-SOLUTIONS AB Here we describe a simple method to estimate the inner-sphere hydration state of the Mn(II) ion in coordination complexes and metalloproteins. The line width of bulk (H2O)-O-17 is measured in the presence and absence of Mn(11) as a function of temperature, and transverse O-17 relaxivities are calculated. It is demonstrated that the maximum O-17 relaxivity is directly proportional to the number of inner-sphere water ligands (q). Using a combination of literature data and experimental data for 12 Mn(II) complexes, we show that this method provides accurate estimates of q with an uncertainty of +/- 0.2 water molecules. The method can be implemented on commercial NMR spectrometers working at fields of 7 T and higher. The hydration number can be obtained for micromolar Mn(II) concentrations. We show that the technique can be extended to metalloproteins or complex:protein interactions. For example, Mn(II) binds to the multimetal binding site A on human serum albumin with two inner-sphere water ligands that undergo rapid exchange (1.06 x 10(8) s(-1) at 37 degrees C). The possibility of extending this technique to other metal ions such as Gd(III) is discussed. C1 [Gale, Eric M.; Zhu, Jiang; Caravan, Peter] Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Massachusetts Gen Hosp,Med Sch, Charlestown, MA 02129 USA. RP Caravan, P (reprint author), Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Massachusetts Gen Hosp,Med Sch, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM caravan@nmr.mgh.harvard.edu FU National Cancer Institute [CA161221, CA009502]; National Center for Research Resources [RR023385]; China Scholarship Council [201208510160] FX This work was supported by grants from the National Cancer Institute (CA161221 to P.C. and a T32 postdoctoral fellowship to E.M.G., CA009502), and an instrument grant (RR023385) from National Center for Research Resources. J.Z. (North Sichuan Medical College) is supported by the China Scholarship Council (File No. 201208510160). We would like to thank Prof. Jack Szostak for access to a 9.4 T NMR spectrometer. NR 100 TC 18 Z9 18 U1 4 U2 34 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 11 PY 2013 VL 135 IS 49 BP 18600 EP 18608 DI 10.1021/ja4094132 PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA 272CU UT WOS:000328438700055 PM 24088013 ER PT J AU Lim, MM Elkind, J Xiong, GX Galante, R Zhu, JX Zhang, L Lian, J Rodin, J Kuzma, NN Pack, AI Cohen, AS AF Lim, Miranda M. Elkind, Jaclynn Xiong, Guoxiang Galante, Ray Zhu, Jingxu Zhang, Lin Lian, Jie Rodin, Julianna Kuzma, Nicholas N. Pack, Allan I. Cohen, Akiva S. TI Dietary Therapy Mitigates Persistent Wake Deficits Caused by Mild Traumatic Brain Injury SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID CHAIN AMINO-ACIDS; FLUID-PERCUSSION MODEL; SLEEP-DEPRIVATION; SUSTAINED ATTENTION; ALZHEIMERS-DISEASE; RATS; MICE; METABOLISM; WAKEFULNESS; PREVALENCE AB Sleep disorders are highly prevalent in patients with traumatic brain injury (TBI) and can significantly impair cognitive rehabilitation. No proven therapies exist to mitigate the neurocognitive consequences of TBI. We show that mild brain injury in mice causes a persistent inability to maintain wakefulness and decreases orexin neuron activation during wakefulness. We gave mice a dietary supplement of branched-chain amino acids (BCAAs), precursors for de novo glutamate synthesis in the brain. BCAA therapy reinstated activation of orexin neurons and improved wake deficits in mice with mild brain injury. Our data suggest that dietary BCAA intervention, acting in part through orexin, can ameliorate injury-induced sleep disturbances and may facilitate cognitive rehabilitation after brain injury. C1 [Lim, Miranda M.; Pack, Allan I.] Univ Penn, Perelman Sch Med, Dept Med, Div Sleep Med, Philadelphia, PA 19104 USA. [Lim, Miranda M.] Univ Penn, Perelman Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. [Lim, Miranda M.; Galante, Ray; Zhu, Jingxu; Zhang, Lin; Lian, Jie; Rodin, Julianna; Pack, Allan I.] Univ Penn, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USA. [Elkind, Jaclynn; Xiong, Guoxiang; Cohen, Akiva S.] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. [Kuzma, Nicholas N.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Cohen, Akiva S.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Lim, MM (reprint author), Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Div Hosp & Specialty Med, Sleep Disorders Lab, Portland, OR 92739 USA. EM lmir@ohsu.edu FU NIH [T32 HL007713, R01HL111725-01A1, R01NS069629, R01HD059288]; University of Pennsylvania Department of Medicine/Measey Research Fellowship FX Supported by NIH T32 HL007713 and University of Pennsylvania Department of Medicine/Measey Research Fellowship to M. M. L., NIH R01HL111725-01A1 to A.I P., and NIH R01NS069629 and R01HD059288 to A.S.C. NR 51 TC 15 Z9 15 U1 2 U2 12 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD DEC 11 PY 2013 VL 5 IS 215 AR 215ra173 DI 10.1126/scitranslmed.3007092 PG 12 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 275OA UT WOS:000328685500004 PM 24337480 ER PT J AU Lawson, KA Teteak, CJ Gao, JD Li, N Hacquebord, J Ghatan, A Zielinska-Kwiatkowska, A Song, GC Chansky, HA Yang, L AF Lawson, Kevin A. Teteak, Colin J. Gao, Jidi Li, Ning Hacquebord, Jacques Ghatan, Andrew Zielinska-Kwiatkowska, Anna Song, Guangchun Chansky, Howard A. Yang, Liu TI ESET histone methyltransferase regulates osteoblastic differentiation of mesenchymal stem cells during postnatal bone development SO FEBS LETTERS LA English DT Article DE Epigenetic regulation; Osteoblast differentiation; Mesenchymal stem cell; Bone development ID GROWTH-PLATE; INTERACTS; CHONDROCYTES; EXPRESSION; MATURATION; H3-K9; RUNX2 AB To investigate the effects of histone methyltransferase ESET (also known as SETDB1) on bone metabolism, we analyzed osteoblasts and osteoclasts in ESET knockout animals, and performed osteogenesis assays using ESET-null mesenchymal stem cells. We found that ESET deletion severely impairs osteoblast differentiation but has no effect on osteoclastogenesis, that co-transfection of ESET represses Runx2-mediated luciferase reporter while siRNA knockdown of ESET activates the luciferase reporter in mesenchymal cells, and that ESET is required for postnatal expression of Indian hedgehog protein in the growth plate. As the bone phenotype in ESET-null mice is 100% penetrant, these results support ESET as a critical regulator of osteoblast differentiation during bone development. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 [Lawson, Kevin A.; Teteak, Colin J.; Gao, Jidi; Hacquebord, Jacques; Ghatan, Andrew; Zielinska-Kwiatkowska, Anna; Chansky, Howard A.; Yang, Liu] Univ Washington, Dept Orthoped & Sports Med, Seattle, WA 98195 USA. [Li, Ning; Chansky, Howard A.; Yang, Liu] VA Puget Sound Hlth Care Syst, Res & Dev, Seattle, WA 98108 USA. [Song, Guangchun] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. RP Yang, L (reprint author), Univ Washington, Dept Orthoped & Sports Med, 1660 S Columbian Way,GMR 151, Seattle, WA 98108 USA. EM lyang@u.washington.edu FU NIH [RO1 AR051455]; VA Merit Review Award from the U.S. Department of Veterans Affairs, Office of Research and Development Biomedical Laboratory Research Program FX We thank Dr. Y. Shinkai for frozen mouse embryos harboring (exon 15 & 16)-floxed ESET allele, Dr. J.J. Westendorf for pOG2-Luc, Dr. G. Karsenty for pCMV-HA-Runx2 plasmid, S.L. Carey for assistance in mouse breeding, and Dr. Roberto Nicosia's lab for assistance in image acquisition. This work is supported in part by NIH grant RO1 AR051455 (to L.Y.), and by a VA Merit Review Award from the U.S. Department of Veterans Affairs, Office of Research and Development Biomedical Laboratory Research Program (to H.A.C.). NR 17 TC 10 Z9 10 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 EI 1873-3468 J9 FEBS LETT JI FEBS Lett. PD DEC 11 PY 2013 VL 587 IS 24 BP 3961 EP 3967 DI 10.1016/j.febslet.2013.10.028 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 257QI UT WOS:000327400100012 PM 24188826 ER PT J AU Mateen, FJ Post, WS Sacktor, N Abraham, AG Becker, JT Smith, BR Detels, R Martin, E Phair, JP Shinohara, RT AF Mateen, Farrah J. Post, Wendy S. Sacktor, Ned Abraham, Alison G. Becker, James T. Smith, Bryan R. Detels, Roger Martin, Eileen Phair, John P. Shinohara, Russell T. CA Multictr AIDS Cohort Study MACS TI Long-term predictive value of the Framingham Risk Score for Stroke in HIV-positive vs HIV-negative men SO NEUROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS-INFECTION; ACTIVE ANTIRETROVIRAL THERAPY; MULTICENTER AIDS COHORT; CEREBROVASCULAR-DISEASE; ISCHEMIC-STROKE; UNITED-STATES; SOUTH-AFRICA; EVENTS; YOUNG AB Objective: To test the predictive accuracy of the Framingham Risk Score for Stroke (FRS-S) in HIV-infected (HIV+) vs HIV-uninfected (HIV-) men. Methods: The Multicenter AIDS Cohort Study (MACS) is an ongoing prospective study of HIV+ and HIV- men who have sex with men (MSM) enrolled in 4 US cities. We ascertained all reported stroke events during a recent 15-year timeframe (July 1, 1996 to June 30, 2011) among 3,945 participants (1,776 HIV+ and 2,169 HIV-). For those with strokes, FRS-S were calculated 10 years before the stroke event and assessed according to HIV status. Results: A total of 114 stroke events occurred, including 57 HIV+ and 37 HIV- participants with first-ever strokes and 19 fatal strokes. The incidence of first-ever stroke was 1.7/1,000 person-years among HIV- and 3.3/1,000 person-years among HIV+ participants. Among those with strokes, HIV +/- participants were younger than HIV+participants (median age 51.3 vs 61.8 years, p < 0.0001). For these men with stroke, the average 10-year risk of stroke was higher for HIV+ MSM (6.6% [range 3%-26%] vs 4.9% for HIV- MSM [range 0%-15%], p < 0.04). Traditional risk factors for stroke were similar among the Framingham cohort and the MACS HIV+ and HIV- participants. Conclusions: FRS-S prediction was systematically different in HIV+ vs HIV- men with stroke events. The FRS-S underestimates the long-term risk of stroke in HIV+ men. C1 [Mateen, Farrah J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Mateen, Farrah J.; Sacktor, Ned] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. [Post, Wendy S.; Abraham, Alison G.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Post, Wendy S.] Johns Hopkins Univ, Dept Med, Div Cardiol, Baltimore, MD USA. [Sacktor, Ned; Smith, Bryan R.] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA. [Becker, James T.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Becker, James T.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. [Becker, James T.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. [Detels, Roger] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. [Detels, Roger] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Martin, Eileen] Rush Univ, Dept Psychiat, Med Ctr, Chicago, IL 60612 USA. [Phair, John P.] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60611 USA. [Shinohara, Russell T.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. RP Mateen, FJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM fmateen@partners.org FU Canadian Institutes of Health Research; National Institute of Allergy and Infectious Diseases; National Cancer Institute [UO1-AI-35042, UL1-RR025005 (GCRC), UO1-AI-35043, UO1-AI-35039, UO1-AI-35040, UO1-AI-35041] FX F.J.M. is supported by an HIV/AIDS priority fellowship grant from the Canadian Institutes of Health Research. The MACS is funded by the National Institute of Allergy and Infectious Diseases, with additional supplemental funding from the National Cancer Institute: UO1-AI-35042, UL1-RR025005 (GCRC), UO1-AI-35043, UO1-AI-35039, UO1-AI-35040, and UO1-AI-35041. NR 34 TC 17 Z9 17 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD DEC 10 PY 2013 VL 81 IS 24 BP 2094 EP 2102 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA AA0FZ UT WOS:000330772300011 PM 24212385 ER PT J AU Miller, RG Brooks, BR Swain-Eng, RJ Basner, RC Carter, GT Casey, P Cohen, AB Dubinsky, R Forshew, D Jackson, CE Kasarskis, E Procaccini, NJ Sanjak, M Tolin, FP AF Miller, Robert G. Brooks, Benjamin Rix Swain-Eng, Rebecca J. Basner, Robert C. Carter, Gregory T. Casey, Patricia Cohen, Adam B. Dubinsky, Richard Forshew, Dallas Jackson, Carlayne E. Kasarskis, Ed Procaccini, Nicholas J. Sanjak, Mohammed Tolin, Fredrik P. TI Quality improvement in neurology: Amyotrophic lateral sclerosis quality measures Report of the Quality Measurement and Reporting Subcommittee of the American Academy of Neurology SO NEUROLOGY LA English DT Article ID PRACTICE PARAMETER UPDATE; STANDARDS SUBCOMMITTEE; MULTIDISCIPLINARY CARE; OF-LIFE; MANAGEMENT; PATIENT; DISEASE; ALS; SURVIVAL C1 [Miller, Robert G.; Forshew, Dallas] Calif Pacific Med Ctr, Forbes Norris MDA ALS Res Ctr, San Francisco, CA 94114 USA. Carolinas HealthCare Syst, Carolinas Neuromuscular ALS MDA Ctr, Charlotte, NC USA. [Brooks, Benjamin Rix; Sanjak, Mohammed] Univ N Carolina, Sch Med, Dept Neurol, Charlotte, NC 28223 USA. [Sanjak, Mohammed] Univ N Carolina, Sch Med, Dept Kinesiol, Carolinas Med Ctr, Charlotte, NC 28223 USA. [Swain-Eng, Rebecca J.] Amer Acad Neurol, Minneapolis, MN USA. [Basner, Robert C.] Columbia Univ Coll Phys & Surg, Div Pulm Med, New York, NY 10032 USA. [Carter, Gregory T.] St Lukes Rehabil Inst, Spokane, WA USA. [Casey, Patricia] Northwestern Med Fac Fdn, Dept Neurol, Chicago, IL USA. [Cohen, Adam B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cohen, Adam B.] Harvard Univ, Sch Med, Boston, MA USA. [Dubinsky, Richard] Univ Kansas, Dept Neurol, Kansas City, KS USA. [Jackson, Carlayne E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Neurol, San Antonio, TX 78229 USA. [Kasarskis, Ed] Univ Kentucky, Dept Neurol, Lexington, KY 40536 USA. [Procaccini, Nicholas J.] Swedish Med Ctr, Seattle, WA USA. [Procaccini, Nicholas J.] Univ Washington, Seattle, WA 98195 USA. [Tolin, Fredrik P.] Humana, Chicago, IL USA. RP Miller, RG (reprint author), Calif Pacific Med Ctr, Forbes Norris MDA ALS Res Ctr, San Francisco, CA 94114 USA. FU Muscular Dystrophy Association; AB Science; Acorda; ALS Therapy Alliance; Asubio; Avanir; Biogen Idec; Bristol-Myers Squibb; Cytokinetics; GlaxoSmithKline; Knopp Bioscience; Neuraltus; National Institute of Neurological Disorders and Stroke Clinical Research Consortium; NHLBI/NIH [R01HL103676-01A1 NIH/NHLBI, R01HL093081 NIH/NHLBI]; Knopp Pharmaceuticals; ATSDR FX R. Miller has received research support from the Muscular Dystrophy Association and is a consultant for Cytokinetics and Asubio Pharmaceuticals. B. Brooks has received funding and/or research grants from AB Science, Acorda, ALS Therapy Alliance, Asubio, Avanir, Biogen Idec, Bristol-Myers Squibb, Cytokinetics, GlaxoSmithKline, Knopp Bioscience, Muscular Dystrophy Association, Neuraltus, National Institute of Neurological Disorders and Stroke Clinical Research Consortium, Quest-Cor, and Teva. R. Swain-Eng is a full-time employee of the American Academy of Neurology. R. Basner is principal investigator of a Muscular Dystrophy Association grant, Opto-Electronic Plethysmography (OEP): A novel non-invasive quantitative assessment of lower rib cage paradox and use of accessory muscles in patients with amyotrophic lateral sclerosis; Site Investigator and Sleep Protocol Subcommittee member of an NHLBI/NIH grant, Sleep-Disordered Breathing During Pregnancy and Risks to Cardiovascular Health; and coinvestigator of the following: R01HL103676-01A1 NIH/NHLBI, Subclinical Interstitial Lung Disease in MESA; R01HL093081 NIH/NHLBI, Pulmonary Vascular Changes in Early COPD; and InterMune PIPF-016, a randomized, double-blind, placebo- controlled, phase 3 study of the efficacy and safety of Pirfenidone in patients with Idiopathic Pulmonary Fibrosis (IPF). G. Carter reports no disclosures. P. Casey is a full-time employee of Northwestern Medical Faculty Foundation, Department of Neurology. A. Cohen reports no disclosures. R. Dubinsky reports disclosures for relationships with Allergan Pharmaceuticals, NIH, and AHRQ. D. Forshew is a consultant for Questcor and Asubio Pharmaceuticals. C. Jackson has received research support from Knopp Pharmaceuticals, Biogen Idec, and Cytokinetics. E. Kasarskis is a consultant for Asubio Pharmaceuticals and ATSDR. N. Procaccini reports no disclosures. M. Sanjak reports no disclosures. F. Tolin reports no disclosures. Go to Neurology.org for full disclosures. NR 31 TC 16 Z9 17 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD DEC 10 PY 2013 VL 81 IS 24 BP 2136 EP 2140 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA AA0FZ UT WOS:000330772300018 PM 24271651 ER PT J AU Kim, JI Stott, RT Soohoo, J Lee, KM Zhao, GP Yeh, H Deng, SP Markmann, JF AF Kim, James I. Stott, Ryan T. Soohoo, Julie Lee, Kang Mi Zhao, Gaoping Yeh, Heidi Deng, Shaoping Markmann, James F. TI Elevated Levels of Interferon-gamma Production by Memory T Cells Do Not Promote Transplant Tolerance Resistance in Aged Recipients SO PLOS ONE LA English DT Article ID IFN-GAMMA; CYTOKINE PRODUCTION; THYMIC INVOLUTION; IN-VIVO; ALLOGRAFT-REJECTION; HETEROLOGOUS IMMUNITY; PERIPHERAL TOLERANCE; ALLOIMMUNE RESPONSES; TYPE-2 CYTOKINES; EFFECTOR-CELLS AB Immunosenescence predisposes the elderly to infectious and autoimmune diseases and impairs the response to vaccination. We recently demonstrated that ageing also impedes development of transplantation tolerance. Unlike their young counterparts (8-12 weeks of age) aged male recipients (greater than 12 months of age) transplanted with a full MHC-mismatched heart are resistant to tolerance mediated by anti-CD45RB antibody. Surprisingly, either chemical or surgical castration restored tolerance induction to levels observed using young recipients. Based on the strong impact of endocrine modulation on transplant tolerance, we explored the impact of ageing and castration on the immune system. Here we report a significant increase in the percentage of T cells that produce interferon-gamma (IFN gamma) in aged male versus young male animals and that the overall increase in IFN-gamma production was due to an expansion of IFN-gamma-producing memory T cells in aged animals. In contrast to IFN-gamma production, we did not observe differences in IL-10 expression in young versus old male mice. We hypothesized that endocrine modulation would diminish the elevated levels of IFN-gamma production in aged recipients, however, we observed no significant reduction in the percentage of IFN-gamma+ T cells upon castration. Furthermore, we neutralized interferon-gamma by antibody and did not observe an effect on graft survival. We conclude that while elevated levels of interferon-gamma serves as a marker of tolerance resistance in aged mice, other as yet to be identified factors are responsible for its cause. Defining these factors may be relevant to design of tolerogenic strategies for aged recipients. C1 [Kim, James I.; Stott, Ryan T.; Soohoo, Julie; Lee, Kang Mi; Zhao, Gaoping; Yeh, Heidi; Deng, Shaoping; Markmann, James F.] Harvard Univ, Sch Med, Dept Surg, Transplantat Unit,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Zhao, Gaoping; Deng, Shaoping] Sichuan Prov Peoples Hosp, Dept Surg, Chengdu, Sichuan Provinc, Peoples R China. [Zhao, Gaoping; Deng, Shaoping] Sichuan Acad Med Sci, Chengdu, Sichuan Provinc, Peoples R China. RP Markmann, JF (reprint author), Harvard Univ, Sch Med, Dept Surg, Transplantat Unit,Massachusetts Gen Hosp, Boston, MA 02115 USA. EM jmarkmann@partners.org FU National Institutes of Health (NIH) [RO1AI057851-05, NIH K08-DK094965, NIH 5T32AI7529] FX Funding provided by National Institutes of Health (NIH) RO1AI057851-05 (JFM), NIH K08-DK094965 (HY), and NIH 5T32AI7529 (KML). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 66 TC 1 Z9 1 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 10 PY 2013 VL 8 IS 12 AR e82856 DI 10.1371/journal.pone.0082856 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 275VW UT WOS:000328707400099 PM 24340063 ER PT J AU Oh, H Kim, H Chung, KH Hong, NH Shin, B Park, WJ Jun, Y Rhee, S Song, WK AF Oh, Hyejin Kim, Hwan Chung, Kyung-Hwun Hong, Nan Hyung Shin, Baehyun Park, Woo Jin Jun, Youngsoo Rhee, Sangmyung Song, Woo Keun TI SPIN90 Knockdown Attenuates the Formation and Movement of Endosomal Vesicles in the Early Stages of Epidermal Growth Factor Receptor Endocytosis SO PLOS ONE LA English DT Article ID 2 DISTINCT PHASES; SIGNAL-TRANSDUCTION; CELL-PROLIFERATION; DOWN-REGULATION; ERBB RECEPTORS; EGF RECEPTOR; CYCLIN D1; IN-VIVO; MIGRATION; PATHWAY AB The finding that SPIN90 colocalizes with epidermal growth factor (EGF) in EEA1-positive endosomes prompted us to investigate the role of SPIN90 in endocytosis of the EGF receptor (EGFR). In the present study, we demonstrated that SPIN90 participates in the early stages of endocytosis, including vesicle formation and trafficking. Stable HeLa cells with knockdown of SPIN90 displayed significantly higher levels of surface EGFR than control cells. Analysis of the abundance and cellular distribution of EGFR via electron microscopy revealed that SPIN90 knockdown cells contain residual EGFR at cell membranes and fewer EGFR-containing endosomes, both features that reflect reduced endosome formation. The delayed early endosomal targeting capacity of SPIN90 knockdown cells led to increased EGFR stability, consistent with the observed accumulation of EGFR at the membrane. Small endosome sizes and reduced endosome formation in SPIN90 knockdown cells, observed using fluorescent confocal microscopy, strongly supported the involvement of SPIN90 in endocytosis of EGFR. Overexpression of SPIN90 variants, particularly the SH3, PRD, and CC (positions 643 - 722) domains, resulted in aberrant morphology of Rab5-positive endosomes (detected as small spots located near the cell membrane) and defects in endosomal movement. These findings clearly suggest that SPIN90 participates in the formation and movement of endosomes. Consistent with this, SPIN90 knockdown enhanced cell proliferation. The delay in EGFR endocytosis effectively increased the levels of endosomal EGFR, which triggered activation of ERK1/2 and cell proliferation via upregulation of cyclin D1. Collectively, our findings suggest that SPIN90 contributes to the formation and movement of endosomal vesicles, and modulates the stability of EGFR protein, which affects cell cycle progression via regulation of the activities of downstream proteins, such as ERK1/2, after EGF stimulation. C1 [Oh, Hyejin; Kim, Hwan; Chung, Kyung-Hwun; Song, Woo Keun] GIST, Sch Life Sci, Bio Imaging & Cell Dynam Res Ctr, Gwangju Metrocity, South Korea. [Park, Woo Jin] GIST, Sch Life Sci, Bio Remodeling & Gene Therapy Lab, Gwangju Metrocity, South Korea. [Jun, Youngsoo] GIST, Sch Life Sci, Cell Biol & Membrane Biochem Lab, Gwangju Metrocity, South Korea. [Hong, Nan Hyung] Vanderbilt Univ, Med Ctr, Dept Canc Biol, Nashville, TN 37235 USA. [Rhee, Sangmyung] Chung Ang Univ, Dept Life Sci, Seoul 156756, South Korea. [Shin, Baehyun] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. RP Song, WK (reprint author), GIST, Sch Life Sci, Bio Imaging & Cell Dynam Res Ctr, Cheomdan Gwagi Ro 261, Gwangju Metrocity, South Korea. EM wksong@gist.ac.kr OI Jun, Youngsoo/0000-0002-2387-032X FU Bio Imaging and Cell Dynamics Research Center through the National Research Foundation of Korea (NRF) [2007-0056492]; Converging Research Center Program through the National Research Foundation of Korea (NRF) [2013K000381]; Basic Science Research Program through the National Research Foundation of Korea (NRF) [2010-0024096]; Ministry of Education, Science and Technology FX This research was supported by the Bio Imaging and Cell Dynamics Research Center (2007-0056492), the Converging Research Center Program (2013K000381), and Basic Science Research Program through the National Research Foundation of Korea (NRF, Sangmyung Rhee: 2010-0024096) funded by the Ministry of Education, Science and Technology. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 49 TC 2 Z9 2 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 10 PY 2013 VL 8 IS 12 AR e82610 DI 10.1371/journal.pone.0082610 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 275VW UT WOS:000328707400089 PM 24340049 ER PT J AU Tsai, AC Scott, JA Hung, KJ Zhu, JQ Matthews, LT Psaros, C Tomlinson, M AF Tsai, Alexander C. Scott, Jennifer A. Hung, Kristin J. Zhu, Jennifer Q. Matthews, Lynn T. Psaros, Christina Tomlinson, Mark TI Reliability and Validity of Instruments for Assessing Perinatal Depression in African Settings: Systematic Review and Meta-Analysis SO PLOS ONE LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; COMMON MENTAL-DISORDERS; COMMUNITY-HEALTH WORKERS; MIDDLE-INCOME COUNTRIES; POSTNATAL-DEPRESSION; PRIMARY-CARE; NIGERIAN WOMEN; POSTPARTUM DEPRESSION; GLOBAL BURDEN; SOUTH-AFRICA AB Background: A major barrier to improving perinatal mental health in Africa is the lack of locally validated tools for identifying probable cases of perinatal depression or for measuring changes in depression symptom severity. We systematically reviewed the evidence on the reliability and validity of instruments to assess perinatal depression in African settings. Methods and Findings: Of 1,027 records identified through searching 7 electronic databases, we reviewed 126 full-text reports. We included 25 unique studies, which were disseminated in 26 journal articles and 1 doctoral dissertation. These enrolled 12,544 women living in nine different North and sub-Saharan African countries. Only three studies (12%) used instruments developed specifically for use in a given cultural setting. Most studies provided evidence of criterion-related validity (20 [80%]) or reliability (15 [60%]), while fewer studies provided evidence of construct validity, content validity, or internal structure. The Edinburgh postnatal depression scale (EPDS), assessed in 16 studies (64%), was the most frequently used instrument in our sample. Ten studies estimated the internal consistency of the EPDS (median estimated coefficient alpha, 0.84; interquartile range, 0.71-0.87). For the 14 studies that estimated sensitivity and specificity for the EPDS, we constructed 2 x 2 tables for each cut-off score. Using a bivariate random-effects model, we estimated a pooled sensitivity of 0.94 (95% confidence interval [CI], 0.68-0.99) and a pooled specificity of 0.77 (95% CI, 0.59-0.88) at a cut-off score of >= 9, with higher cut-off scores yielding greater specificity at the cost of lower sensitivity. Conclusions: The EPDS can reliably and validly measure perinatal depression symptom severity or screen for probable postnatal depression in African countries, but more validation studies on other instruments are needed. In addition, more qualitative research is needed to adequately characterize local understandings of perinatal depression-like syndromes in different African contexts. C1 [Tsai, Alexander C.; Matthews, Lynn T.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Tsai, Alexander C.; Psaros, Christina] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Tsai, Alexander C.; Scott, Jennifer A.; Matthews, Lynn T.; Psaros, Christina] Harvard Univ, Sch Med, Boston, MA USA. [Scott, Jennifer A.; Hung, Kristin J.] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02215 USA. [Scott, Jennifer A.] Brigham & Womens Hosp, Div Womens Hlth, Boston, MA 02115 USA. [Scott, Jennifer A.] Harvard Humanitarian Initiat, Cambridge, MA USA. [Zhu, Jennifer Q.] Harvard Univ, Cambridge, MA USA. [Matthews, Lynn T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Matthews, Lynn T.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. [Tomlinson, Mark] Univ Stellenbosch, Dept Psychol, Ctr Publ Mental Hlth, ZA-7600 Stellenbosch, South Africa. RP Tsai, AC (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. EM actsai@partners.org OI Tsai, Alexander/0000-0001-6397-7917 FU U.S. National Institutes of Health (NIH) [K23 MH-096620, NIH K23 MH-095655, NIH K23 MH-096651]; National Research Foundation (South Africa); Department for International Development FX The authors received no specific funding to conduct this study but acknowledge the following sources of salary support: U.S. National Institutes of Health (NIH) K23 MH-096620 (ACT), NIH K23 MH-095655 (LTM), NIH K23 MH-096651 (CP), and the National Research Foundation (South Africa) and the Department for International Development (MT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 98 TC 21 Z9 21 U1 1 U2 11 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 2013 VL 8 IS 12 AR UNSP e82521 DI 10.1371/journal.pone.0082521 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 275VW UT WOS:000328707400078 PM 24340036 ER PT J AU Pastor-Perez, FJ Manzano-Fernandez, S Goya-Esteban, R Pascual-Figal, DA Bravo, IPG Barquero-Perez, O Rojo-Alvarez, JL Januzzi, JL Chavarri, MV Garcia-Alberola, A AF Pastor-Perez, Francisco J. Manzano-Fernandez, Sergio Goya-Esteban, Rebeca Pascual-Figal, Domingo A. Garrido Bravo, Iris P. Barquero-Perez, Oscar Luis Rojo-Alvarez, Jose Januzzi, James L. Valdes Chavarri, Mariano Garcia-Alberola, Arcadio TI Heart rate control in chronic heart failure: Resting versus mean heart rate with prolonged ambulatory ECG recording SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Letter DE Heart failure; Heart rate; Holter monitoring ID CORONARY-ARTERY-DISEASE; EUROPEAN-SOCIETY; TASK-FORCE; COLLABORATION; ASSOCIATION; GUIDELINES; DIAGNOSIS; ESC; HFA C1 [Pastor-Perez, Francisco J.; Manzano-Fernandez, Sergio; Pascual-Figal, Domingo A.; Garrido Bravo, Iris P.; Valdes Chavarri, Mariano; Garcia-Alberola, Arcadio] Univ Hosp Virgen Arrixaca, Dept Cardiol, Murcia 30120, Spain. [Goya-Esteban, Rebeca; Barquero-Perez, Oscar; Luis Rojo-Alvarez, Jose] Univ Rey Juan Carlos, Dept Signal Theory & Commun, Madrid, Spain. [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Pastor-Perez, FJ (reprint author), Univ Hosp Virgen Arrixaca, Dept Cardiol, Ctra Madrid Cartagena S-N, Murcia 30120, Spain. EM franpastor79@hotmail.com RI Goya-Esteban, Rebeca/C-6409-2013; Barquero-Perez, Oscar/C-6425-2013; OI Pascual Figal, Domingo A./0000-0002-4993-9540 NR 7 TC 2 Z9 3 U1 0 U2 12 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD DEC 10 PY 2013 VL 170 IS 2 BP E45 EP E47 DI 10.1016/j.ijcard.2013.10.071 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 264OU UT WOS:000327889200011 PM 24210421 ER PT J AU Naumann, RW Coleman, RL Burger, RA Sausville, EA Kutarska, E Ghamande, SA Gabrail, NY DePasquale, SE Nowara, E Gilbert, L Gersh, RH Teneriello, MG Harb, WA Konstantinopoulos, PA Penson, RT Symanowski, JT Lovejoy, CD Leaman, CP Morgenstern, DE Messmann, RA AF Naumann, R. Wendel Coleman, Robert L. Burger, Robert A. Sausville, Edward A. Kutarska, Elzbieta Ghamande, Sharad A. Gabrail, Nashat Y. DePasquale, Stephen E. Nowara, Elzbieta Gilbert, Lucy Gersh, Robert H. Teneriello, Michael G. Harb, Wael A. Konstantinopoulos, Panagiotis A. Penson, Richard T. Symanowski, James T. Lovejoy, Chandra D. Leaman, Christopher P. Morgenstern, David E. Messmann, Richard A. TI PRECEDENT: A Randomized Phase II Trial Comparing Vintafolide (EC145) and Pegylated Liposomal Doxorubicin (PLD) in Combination Versus PLD Alone in Patients With Platinum-Resistant Ovarian Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SOLID TUMORS; FOLATE; CONJUGATE; STRATEGIES AB Purpose Vintafolide (EC145) is a folic acid-desacetylvinblastine conjugate that binds to the folate receptor (FR), which is expressed on the majority of epithelial ovarian cancers. This randomized phase II trial evaluated vintafolide combined with pegylated liposomal doxorubicin (PLD) compared with PLD alone. The utility of an FR-targeted imaging agent, Tc-99m-etarfolatide (EC20), in selecting patients likely to benefit from vintafolide was also examined. Patients and Methods Women with recurrent platinum-resistant ovarian cancer who had undergone two prior cytotoxic regimens were randomly assigned at a 2:1 ratio to PLD (50 mg/m(2) intravenously [IV] once every 28 days) with or without vintafolide (2.5 mg IV three times per week during weeks 1 and 3). Etarfolatide scanning was optional. The primary objective was to compare progression-free survival (PFS) between the groups. Results The intent-to-treat population comprised 149 patients. Median PFS was 5.0 and 2.7 months for the vintafolide plus PLD and PLD-alone arms, respectively (hazard ratio [HR], 0.63; 95% CI, 0.41 to 0.96; P = .031). The greatest benefit was observed in patients with 100% of lesions positive for FR, with median PFS of 5.5 compared with 1.5 months for PLD alone (HR, 0.38; 95% CI, 0.17 to 0.85; P = .013). The group of patients with FR-positive disease (10% to 90%) experienced some PFS improvement (HR, 0.873), whereas patients with disease that did not express FR experienced no PFS benefit (HR, 1.806). Conclusion Vintafolide plus PLD is the first combination to demonstrate an improvement over standard therapy in a randomized trial of patients with platinum-resistant ovarian cancer. Etarfolatide can identify patients likely to benefit from vintafolide. C1 [Naumann, R. Wendel; Symanowski, James T.] Carolinas Med Ctr, Levine Canc Inst, Charlotte, NC 28204 USA. [Coleman, Robert L.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Teneriello, Michael G.] Texas Oncol, Austin, TX USA. [Burger, Robert A.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Sausville, Edward A.] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Kutarska, Elzbieta] Ctr Onkol Ziemi Lubelskiej, Lubland, Poland. [Nowara, Elzbieta] Inst Marii Sklodowskiej Curie, Gliwice, Poland. [Ghamande, Sharad A.] Georgia Hlth Sci Univ, Augusta, GA USA. [Gabrail, Nashat Y.] Gabrail Canc Ctr, Canton, OH USA. [DePasquale, Stephen E.] Chattanoogas Program Womens Oncol, Chattanooga, TN USA. [Gilbert, Lucy] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Gersh, Robert H.] Canc Care Northwest, Spokane, WA USA. [Lovejoy, Chandra D.; Leaman, Christopher P.; Morgenstern, David E.; Messmann, Richard A.] Endocyte, W Lafayette, IN USA. [Konstantinopoulos, Panagiotis A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Penson, Richard T.] Massachusetts Gen Hosp, Dana Farber Canc Ctr, Boston, MA 02114 USA. RP Naumann, RW (reprint author), Carolinas Med Ctr, Levine Canc Inst, 1025 Morehead Med Dr,Suite 600, Charlotte, NC 28204 USA. EM wnaumann@mac.com OI Morgenstern, Dave/0000-0003-0554-3947 FU Endocyte (West Lafayette, IN); Ann Rife Cox Chair for Gynecology; Endocyte FX Supported by Endocyte (West Lafayette, IN) and in part by Ann Rife Cox Chair for Gynecology (R.L.C.); medical writing and editorial assistance was provided by TRM Oncology (the Hague, the Netherlands; supported by Endocyte). NR 17 TC 69 Z9 70 U1 1 U2 15 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 2013 VL 31 IS 35 BP 4400 EP + DI 10.1200/JCO.2013.49.7685 PG 9 WC Oncology SC Oncology GA 277KJ UT WOS:000328817400005 PM 24127448 ER PT J AU El-Jawahri, A Chen, YB AF El-Jawahri, Areej Chen, Yi-Bin TI Pleiotropic Approach to Graft-Versus-Host Disease SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HEMATOPOIETIC-CELL TRANSPLANTATION; COA REDUCTASE INHIBITORS; T-CELLS; AUTOIMMUNE-DISEASE; IL-10 PRODUCTION; STATINS; IMMUNOMODULATION; ATORVASTATIN; PRAVASTATIN; ACTIVATION C1 [El-Jawahri, Areej] Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP El-Jawahri, A (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 32 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 10 PY 2013 VL 31 IS 35 BP 4462 EP 4464 DI 10.1200/JCO.2013.52.8182 PG 3 WC Oncology SC Oncology GA 277KJ UT WOS:000328817400013 PM 24166516 ER PT J AU Meyerhardt, JA Mangu, PB Flynn, PJ Korde, L Loprinzi, CL Minsky, BD Petrelli, NJ Ryan, K Schrag, DH Wong, SL Benson, AB AF Meyerhardt, Jeffrey A. Mangu, Pamela B. Flynn, Patrick J. Korde, Larissa Loprinzi, Charles L. Minsky, Bruce D. Petrelli, Nicholas J. Ryan, Kim Schrag, Deborah H. Wong, Sandra L. Benson, Al B., III TI Follow-Up Care, Surveillance Protocol, and Secondary Prevention Measures for Survivors of Colorectal Cancer: American Society of Clinical Oncology Clinical Practice Guideline Endorsement SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RECTAL-CANCER; COLON; UPDATE; DIAGNOSIS; RISK AB Purpose The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for endorsing recent clinical practice guidelines that have been developed by other professional organizations. Methods The Cancer Care Ontario (CCO) Guideline on Follow-up Care, Surveillance Protocol, and Secondary Prevention Measures for Survivors of Colorectal Cancer was reviewed by ASCO for methodologic rigor and considered for endorsement. Results The ASCO Panel concurred with the CCO recommendations and recommended endorsement, with the addition of several qualifying statements. Conclusion Surveillance should be guided by presumed risk of recurrence and functional status of the patient (important within the first 2 to 4 years). Medical history, physical examination, and carcinoembryonic antigen testing should be performed every 3 to 6 months for 5 years. Patients at higher risk of recurrence should be considered for testing in the more frequent end of the range. A computed tomography scan (abdominal and chest) is recommended annually for 3 years, in most cases. Positron emission tomography scans should not be used for surveillance outside of a clinical trial. A surveillance colonoscopy should be performed 1 year after the initial surgery and then every 5 years, dictated by the findings of the previous one. If a colonoscopy was not preformed before diagnosis, it should be done after completion of adjuvant therapy (before 1 year). Secondary prevention (maintaining a healthy body weight and active lifestyle) is recommended. If a patient is not a candidate for surgery or systemic therapy because of severe comorbid conditions, surveillance tests should not be performed. A treatment plan from the specialist should have clear directions on appropriate follow-up by a nonspecialist. C1 [Meyerhardt, Jeffrey A.; Schrag, Deborah H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mangu, Pamela B.] Amer Soc Clin Oncol, Alexandria, VA 22314 USA. [Ryan, Kim] Fight Colorectal Canc, Alexandria, VA USA. [Flynn, Patrick J.] Minnesota Oncol, Minneapolis, MN USA. [Loprinzi, Charles L.] Mayo Clin, Rochester, MN USA. [Korde, Larissa] Univ Washington, Seattle, WA 98195 USA. [Minsky, Bruce D.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Petrelli, Nicholas J.] Helen Graham Canc Ctr, Newark, DE USA. [Wong, Sandra L.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Benson, Al B., III] Northwestern Univ, Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. RP Meyerhardt, JA (reprint author), Amer Soc Clin Oncol, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA. NR 20 TC 60 Z9 62 U1 0 U2 10 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 10 PY 2013 VL 31 IS 35 BP 4465 EP + DI 10.1200/JCO.2013.50.7442 PG 8 WC Oncology SC Oncology GA 277KJ UT WOS:000328817400014 PM 24220554 ER PT J AU Robinson, AI Oreskovic, NM AF Robinson, Alyssa I. Oreskovic, Nicolas M. TI Comparing self-identified and census-defined neighborhoods among adolescents using GPS and accelerometer SO INTERNATIONAL JOURNAL OF HEALTH GEOGRAPHICS LA English DT Article DE Neighborhood; Youth; Physical activity; GIS ID GLOBAL POSITIONING SYSTEM; BODY-MASS INDEX; PHYSICAL-ACTIVITY; BUILT ENVIRONMENT; HEALTH RESEARCH; CHILDREN; BEHAVIORS; OBESITY; ASSOCIATIONS; PERCEPTIONS AB Background: Numerous definitions of neighborhood exist, yet few studies have considered youth's perceptions of neighborhood boundaries. This study compared youth-identified neighborhood (YIN) boundaries to census-defined neighborhood (CDN) boundaries, and determined how the amount of time spent and moderate-to-vigorous physical activity (MVPA) levels compared within both boundary types. Methods: Adolescents aged 11-14 years were asked to identify their neighborhood boundaries using a map. Objective location and physical activity data collected using Global Positioning System (GPS) devices and accelerometers were used to calculate the amount of time spent and MVPA within youth-identified and census-defined neighborhood boundaries. Paired bivariate analyses compared mean area (meters squared), percent of total time, daily MVPA (minutes), time density (minutes/m(2)) and MVPA density (minutes/m(2)) for both boundary types. Results: Youth-identified neighborhoods (1,821,705 m(2)) and census-defined neighborhoods (1,277,181 m(2)) were not significantly different in area, p = 0.30. However, subjects spent more time in youth-identified neighborhoods (80.3%) than census-defined neighborhoods (58.4%), p < 0.0001, and engaged in more daily MVPA within youth-identified neighborhoods (14.7 minutes) than census-defined neighborhoods (9.5 minutes), p < 0.0001. After adjusting for boundary area, MVPA density (minutes of MVPA per squared meter of area) remained significantly greater for youth-identified neighborhoods (2.4 x 10(-4) minutes/m(2)) than census-defined neighborhoods (1.4 x 10(-4) minutes/m(2)), p = 0.02. Conclusions: Adolescents perceive their neighborhoods to be similar in size to census-defined neighborhoods. However, youth-identified neighborhoods better capture the locations in which adolescents spend time and engage in physical activity. Asking adolescents to identify their neighborhood boundaries is a feasible and valuable method for identifying the spaces that adolescents are exposed to and use to be physically active. C1 [Robinson, Alyssa I.; Oreskovic, Nicolas M.] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Res & Policy, Boston, MA 02114 USA. [Oreskovic, Nicolas M.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Oreskovic, Nicolas M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Oreskovic, Nicolas M.] Harvard Univ, Sch Med, Boston, MA USA. RP Oreskovic, NM (reprint author), Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Res & Policy, Boston, MA 02114 USA. EM noreskovic@partners.org OI Oreskovic, Nicolas/0000-0001-8702-8636 FU NHLBI NIH HHS [K23 HL103841] NR 52 TC 9 Z9 9 U1 5 U2 25 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-072X J9 INT J HEALTH GEOGR JI Int. J. Health Geogr. PD DEC 10 PY 2013 VL 12 AR 57 DI 10.1186/1476-072X-12-57 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 273VL UT WOS:000328564300001 PM 24325342 ER PT J AU Neilan, TG Shah, RV Abbasi, SA Farhad, H Groarke, JD Dodson, JA Coelho, O McMullan, CJ Heydari, B Michaud, GF John, RM van der Geest, R Steigner, ML Blankstein, R Jerosch-Herold, M Kwong, RY AF Neilan, Tomas G. Shah, Ravi V. Abbasi, Siddique A. Farhad, Hoshang Groarke, John D. Dodson, John A. Coelho-Filho, Otavio McMullan, Ciaran J. Heydari, Bobak Michaud, Gregory F. John, Roy M. van der Geest, Rob Steigner, Michael L. Blankstein, Ron Jerosch-Herold, Michael Kwong, Raymond Y. TI The Incidence, Pattern, and Prognostic Value of Left Ventricular Myocardial Scar by Late Gadolinium Enhancement in Patients With Atrial Fibrillation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE atrial fibrillation; cardiac magnetic resonance late; gadolinium enhancement ID CARDIAC MAGNETIC-RESONANCE; RADIOFREQUENCY CATHETER ABLATION; TOMOGRAPHY CORONARY-ANGIOGRAPHY; OF-CARDIOLOGY FOUNDATION; PULMONARY VEIN ISOLATION; COMPUTED-TOMOGRAPHY; HYPERTROPHIC CARDIOMYOPATHY; HEART-FAILURE; INTRACARDIAC ECHOCARDIOGRAPHY; EJECTION FRACTION AB Objectives This study sought to identify the frequency, pattern, and prognostic significance of left ventricular (LV) late gadolinium enhancement (LGE) in patients with atrial fibrillation (AF). Background There are limited data on the presence, pattern, and prognostic significance of LV myocardial fibrosis in patients with AF. LGE during cardiac magnetic resonance imaging is a marker for myocardial fibrosis. Methods A group of 664 consecutive patients without known prior myocardial infarction who were referred for radiofrequency ablation of AF were studied. Cardiac magnetic resonance imaging was requested to assess pulmonary venous anatomy. Results Overall, 73% were men, with a mean age of 56 years and a mean LV ejection fraction of 56 +/- 10%. LV LGE was found in 88 patients (13%). The endpoint was all-cause mortality, and in this cohort, 68 deaths were observed over a median follow-up period of 42 months. On univariate analysis, age (hazard ratio [HR]: 1.05; 95% confidence interval [CI]: 1.03 to 1.08; chi-square likelihood ratio [LR chi(2)]: 15.2; p = 0.0001), diabetes (HR: 2.39; 95% CI: 1.41 to 4.09; LR chi(2): 10.3; p = 0.001), a history of heart failure (HR: 1.78; 95% CI: 1.09 to 2.91; LR chi(2) 2: 5.37; p = 0.02), left atrial dimension (HR: 1.04; 95% CI: 1.01 to 1.08; LR chi(2) 2: 6.47; p = 0.01), presence of LGE (HR: 5.08; 95% CI: 3.08 to 8.36; LR chi(2):28.8; p < 0.0001), and LGE extent (HR: 1.15; 95% CI: 1.10 to 1.21; LR chi(2): 35.6; p < 0.0001) provided the strongest associations with mortality. The mortality rate was 8.1% per patient-year in patients with LGE compared with 2.3% patients without LGE. In the best overall multivariate model for mortality, age and the extent of LGE were independent predictors of mortality. Indeed, each 1% increase in the extent of LGE was associated with a 15% increased risk for death. Conclusions In patients with AF, LV LGE is a frequent finding and is a powerful predictor of mortality. (C) 2013 by the American College of Cardiology Foundation C1 [Neilan, Tomas G.; Shah, Ravi V.; Abbasi, Siddique A.; Farhad, Hoshang; Groarke, John D.; Coelho-Filho, Otavio; Heydari, Bobak; Michaud, Gregory F.; John, Roy M.; Blankstein, Ron; Kwong, Raymond Y.] Brigham & Womens Hosp, Cardiovasc Div, Boston, MA 02115 USA. [Neilan, Tomas G.; Shah, Ravi V.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Neilan, Tomas G.] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Dodson, John A.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Coelho-Filho, Otavio] Univ Estadual Campinas, Dept Internal Med, Campinas, Brazil. [McMullan, Ciaran J.] Brigham & Womens Hosp, Dept Med, Div Nephrol, Boston, MA 02115 USA. [van der Geest, Rob] Leiden Univ, Div Image Proc, Med Ctr, Dept Radiol, Leiden, Netherlands. [Steigner, Michael L.; Jerosch-Herold, Michael] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Kwong, RY (reprint author), Brigham & Womens Hosp, Dept Med, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA. EM rykwong@partners.org OI Abbasi, Siddique/0000-0002-9601-7565 FU American Heart Association Fellow to Faculty Grant [12FTF12060588]; NIH; National Institutes of Health [RO1HL090634, RO1HL091157] FX Dr. Neilan is supported by an American Heart Association Fellow to Faculty Grant (12FTF12060588). Dr. Abbassi has received NIH funding. Drs. Jerosch-Herold and Kwong are supported by research grants from the National Institutes of Health (RO1HL090634 and RO1HL091157, respectively). Dr. Shah has served as a consultant for Ventripoint. Dr. John has received a speaking honorarium from St. Jude Medical. Dr. van der Geest is a consultant for Medis Medical Imaging Systems. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 46 TC 25 Z9 25 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 10 PY 2013 VL 62 IS 23 BP 2205 EP 2214 DI 10.1016/j.jacc.2013.07.067 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 267CF UT WOS:000328073000010 PM 23994399 ER PT J AU Gilmore, MS Lebreton, F Van Tyne, D AF Gilmore, Michael S. Lebreton, Francois Van Tyne, Daria TI Dual defensin strategy for targeting Enterococcus faecalis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID SURFACE-PROTEINS; STREPTOCOCCUS-PYOGENES; STAPHYLOCOCCUS-AUREUS; CELL-WALL; ENDOCARDITIS; CONTRIBUTE; SECRETION; INFECTION; VIRULENCE; PEPTIDES C1 [Gilmore, Michael S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02114 USA. RP Gilmore, MS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. EM michael_gilmore@meei.harvard.edu FU NEI NIH HHS [T32 EY007145, EY007145]; NIAID NIH HHS [P01 AI083214, AI083214] NR 19 TC 1 Z9 1 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 10 PY 2013 VL 110 IS 50 BP 19980 EP 19981 DI 10.1073/pnas.1319939110 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 266YY UT WOS:000328061700021 PM 24284170 ER PT J AU Zheng, Y Stephan, MT Gai, SA Abraham, W Shearer, A Irvine, DJ AF Zheng, Yiran Stephan, Matthias T. Gai, S. Annie Abraham, Wuhbet Shearer, Adrianne Irvine, Darrell J. TI In vivo targeting of adoptively transferred T-cells with antibody- and cytokine-conjugated liposomes SO JOURNAL OF CONTROLLED RELEASE LA English DT Article DE Immunoliposomes; Interleukin-2 (IL-2); Cancer immunotherapy; Adoptive cell therapy; Targeted delivery; Melanoma ID METASTATIC MELANOMA; IMMUNOTHERAPY; CANCER; LYMPHOCYTES; THERAPY; IL-2; NANOPARTICLES; REACTIVITY; REGRESSION; RESPONSES AB In adoptive cell therapy (ACT), autologous tumor-specific T-cells isolated from cancer patients are activated and expanded ex vivo, then infused back into the individual to eliminate metastatic tumors. A major limitation of this promising approach is the rapid loss of ACT T-cell effector function in vivo due to the highly immunosuppressive environment in tumors. Protection of T-cells from immunosuppressive signals can be achieved by systemic administration of supporting adjuvant drugs such as interleukins, chemotherapy, and other immunomodulators, but these adjuvant treatments are often accompanied by serious toxicities and may still fail to optimally stimulate lymphocytes in all tumor and lymphoid compartments. Here we propose a novel strategy to repeatedly stimulate or track ACT T-cells, using cytokines or ACT-cell-specific antibodies as ligands to target PEGylated liposomes to transferred T-cells in vivo. Using F(ab')(2) fragments against a unique cell surface antigen on ACT cells (Thy1.1) or an engineered interleukin-2 (IL-2) molecule on an Fc framework as targeting ligands, we demonstrate that >95% of ACT cells can be conjugated with liposomes following a single injection in vivo. Further, we show that IL-2-conjugated liposomes both target ACT cells and are capable of inducing repeated waves of ACT T-cell proliferation in tumor-bearing mice. These results demonstrate the feasibility of repeated functional targeting of T-cells in vivo, which will enable delivery of imaging contrast agents, immunomodulators, or chemotherapy agents in adoptive cell therapy regimens. (C) 2013 The Authors. Published by Elsevier B.V. All rights reserved. C1 [Zheng, Yiran; Shearer, Adrianne; Irvine, Darrell J.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Zheng, Yiran; Stephan, Matthias T.; Gai, S. Annie; Abraham, Wuhbet; Irvine, Darrell J.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Stephan, Matthias T.; Irvine, Darrell J.] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. [Gai, S. Annie] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Irvine, Darrell J.] Ragon Inst Massachusetts Gen Hosp MIT & Harvard U, Boston, MA USA. [Irvine, Darrell J.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Irvine, DJ (reprint author), MIT Room 76-261,77 Massachusetts Ave, Cambridge, MA 02139 USA. EM djirvine@mit.edu FU NIH [CA140476, CA172164]; Dept. of Defense [W81XWH-10-1-0290]; National Cancer Institute [P30-CA14051] FX We thank Prof. K. Dane Wittrup for the gift of engineered IL-2-Fc. This work was supported in part by the NIH (CA140476 and CA172164), the Dept. of Defense (contract W81XWH-10-1-0290), and by the Koch Institute Support (core) Grant P30-CA14051 from the National Cancer Institute. DJI is an investigator of the Howard Hughes Medical Institute. The authors wish to dedicate this paper to the memory of Officer Sean Collier, for his caring service and sacrifice in protecting the MIT community. NR 32 TC 17 Z9 17 U1 1 U2 51 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 EI 1873-4995 J9 J CONTROL RELEASE JI J. Control. Release PD DEC 10 PY 2013 VL 172 IS 2 BP 426 EP 435 DI 10.1016/j.jconrel.2013.05.037 PG 10 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 260NN UT WOS:000327601700006 PM 23770010 ER PT J AU Sherwood, B Wang, L Zhou, XH AF Sherwood, Ben Wang, Lan Zhou, Xiao-Hua TI Weighted quantile regression for analyzing health care cost data with missing covariates SO STATISTICS IN MEDICINE LA English DT Article DE health care cost data; missing data; inverse probability weighting; quantile regression ID LONGITUDINAL DATA; MODELS; FIT AB Analysis of health care cost data is often complicated by a high level of skewness, heteroscedastic variances and the presence of missing data. Most of the existing literature on cost data analysis have been focused on modeling the conditional mean. In this paper, we study a weighted quantile regression approach for estimating the conditional quantiles health care cost data with missing covariates. The weighted quantile regression estimator is consistent, unlike the naive estimator, and asymptotically normal. Furthermore, we propose a modified BIC for variable selection in quantile regression when the covariates are missing at random. The quantile regression framework allows us to obtain a more complete picture of the effects of the covariates on the health care cost and is naturally adapted to the skewness and heterogeneity of the cost data. The method is semiparametric in the sense that it does not require to specify the likelihood function for the random error or the covariates. We investigate the weighted quantile regression procedure and the modified BIC via extensive simulations. We illustrate the application by analyzing a real data set from a health care cost study. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Sherwood, Ben; Wang, Lan] Univ Minnesota, Sch Stat, Minneapolis, MN 55455 USA. [Zhou, Xiao-Hua] VA Puget Sound Hlth Care Syst, HSR&D, Seattle, WA 98101 USA. [Zhou, Xiao-Hua] Univ Washington, Dept Biostat, HSB, Seattle, WA 98198 USA. [Zhou, Xiao-Hua] Renmin Univ China, Sch Stat, Beijing, Peoples R China. RP Zhou, XH (reprint author), Univ Washington, Dept Biostat, HSB, F600,Box 357232, Seattle, WA 98198 USA. EM azhou@u.washington.edu FU National Science Foundation [DMS-1007603]; US Department of Veterans Affairs, Veterans Affairs Health Administration, HSRD grants [RCS 05-196] FX The authors are grateful for the comments from the Associate Editor and the two referees, which help us significantly improve the paper. Wang and Zhou are joint correspondence authors for this paper. National Science Foundation grant DMS-1007603 supported the work of Sherwood and Wang. Xiao-Hua Zhou, PhD, is presently a Core Investigator and Biostatistics Unit Director at the Northwest HSR&D Center of Excellence, Department of Veterans Affairs Medical Center, Seattle, WA, USA. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. Dr. Zhou's work was supported in part by US Department of Veterans Affairs, Veterans Affairs Health Administration, HSR&D grants (RCS 05-196). NR 15 TC 10 Z9 12 U1 0 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD DEC 10 PY 2013 VL 32 IS 28 BP 4967 EP 4979 DI 10.1002/sim.5883 PG 13 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 248UH UT WOS:000326729100008 PM 23836597 ER PT J AU Walling, AM Tisnado, D Asch, SM Malin, JM Pantoja, P Dy, SM Ettner, SL Zisser, AP Schreibeis-Baum, H Lee, M Lorenz, KA AF Walling, Anne M. Tisnado, Diana Asch, Steven M. Malin, Jennifer M. Pantoja, Philip Dy, Sydney M. Ettner, Susan L. Zisser, Ann P. Schreibeis-Baum, Hannah Lee, Martin Lorenz, Karl A. TI The Quality of Supportive Cancer Care in the Veterans Affairs Health System and Targets for Improvement SO JAMA INTERNAL MEDICINE LA English DT Article ID OF-LIFE CARE; EVIDENCE-BASED RECOMMENDATIONS; PALLIATIVE CARE; SYMPTOM MANAGEMENT; MENTAL-HEALTH; END; INTERVENTIONS; DISCUSSIONS; FAMILIES; MEDICARE AB IMPORTANCE Characterizing the quality of supportive cancer care can guide quality improvement. OBJECTIVE To evaluate nonhospice supportive cancer care comprehensively in a national sample of veterans. DESIGN, SETTING, AND PARTICIPANTS Using a retrospective cohort study design, we measured evidence-based cancer care processes using previously validated indicators of care quality in patients with advanced cancer, addressing pain, nonpain symptoms, and information and care planning among 719 veterans with a 2008 Veterans Affairs Central Cancer Registry diagnosis of stage IV colorectal (37.0%), pancreatic (29.8%), or lung (33.2%) cancer. MAIN OUTCOMES AND MEASURES We abstracted medical records from diagnosis for 3 years or until death among eligible veterans (lived >= 30 days following diagnosis with >= 1 Veterans Affairs hospitalization or >= 2 Veterans Affairs outpatient visits). Each indicator identified a clinical scenario and an appropriate action. For each indicator for which a veteran was eligible, we determined whether appropriate care was provided. We also determined patient-level quality overall and by pain, nonpain symptoms, and information and care planning domains. RESULTS Most veterans were older (mean age, 66.2 years), male (97.2%), and white (74.3%). Eighty-five percent received both inpatient and outpatient care, and 92.5% died. Overall, the 719 veterans triggered a mean of 11.7 quality indicators (range, 1-22) and received a mean 49.5% of appropriate care. Notable gaps in care were that inpatient pain screening was common (96.5%) but lacking for outpatients (58.1%). With opioids, bowel prophylaxis occurred for only 52.2% of outpatients and 70.5% of inpatients. Few patients had a timely dyspnea evaluation (15.8%) or treatment (10.8%). Outpatient assessment of fatigue occurred for 31.3%. Of patients at high risk for diarrhea from chemotherapy, 24.2% were offered appropriate antidiarrheals. Only 17.7% of veterans had goals of care addressed in the month after a diagnosis of advanced cancer, and 63.7% had timely discussion of goals following intensive care unit admission. Most decedents (86.4%) were referred to palliative care or hospice before death. Single- vs multiple-fraction radiotherapy should have been considered in 28 veterans with bone metastasis, but none were offered this option. CONCLUSIONS AND RELEVANCE These care gaps reflect important targets for improving the patient and family experience of cancer care. C1 [Walling, Anne M.; Tisnado, Diana; Malin, Jennifer M.; Pantoja, Philip; Ettner, Susan L.; Zisser, Ann P.; Schreibeis-Baum, Hannah; Lee, Martin; Lorenz, Karl A.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Walling, Anne M.; Tisnado, Diana; Lorenz, Karl A.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Walling, Anne M.; Lorenz, Karl A.] RAND Hlth, Santa Monica, CA USA. [Asch, Steven M.] VA Palo Alto Healthcare Syst, Palo Alto, CA USA. [Asch, Steven M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Malin, Jennifer M.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Dy, Sydney M.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Ettner, Susan L.] Univ Calif Los Angeles, Jonathan & Karin Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA 90095 USA. RP Walling, AM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, 911 Broxton Ave, Los Angeles, CA 90095 USA. EM awalling@mednet.ucla.edu OI Schreibeis-Baum, Hannah/0000-0001-7798-9804 FU US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research & Development Service [IIR 09-097] FX This study is based on work supported by the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research & Development Service (project IIR 09-097). NR 44 TC 17 Z9 17 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD DEC 9 PY 2013 VL 173 IS 22 BP 2071 EP 2079 DI 10.1001/jamainternmed.2013.10797 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AA2WL UT WOS:000330954800015 PM 24126685 ER PT J AU Bandopadhayay, P Jabbour, AM Riffkin, C Salmanidis, M Gordon, L Popovski, D Rigby, L Ashley, DM Watkins, DN Thomas, DM Algar, E Ekert, PG AF Bandopadhayay, Pratiti Jabbour, Anissa M. Riffkin, Christopher Salmanidis, Marika Gordon, Lavinia Popovski, Dean Rigby, Lin Ashley, David M. Watkins, David N. Thomas, David M. Algar, Elizabeth Ekert, Paul G. TI The oncogenic properties of EWS/WT1 of desmoplastic small round cell tumors are unmasked by loss of p53 in murine embryonic fibroblasts SO BMC CANCER LA English DT Article ID EWS-WT1 GENE FUSION; LUNG-CANCER; COPY-NUMBER; MICROARRAY; EXPRESSION; IDENTIFICATION; TRANSCRIPTS; INDUCTION; VARIANTS; SURVIVAL AB Background: Desmoplastic small round cell tumor (DSRCT) is characterized by the presence of a fusion protein EWS/WT1, arising from the t (11; 22) (p13;q12) translocation. Here we examine the oncogenic properties of two splice variants of EWS/WT1, EWS/WT1-KTS and EWS/WT1 + KTS. Methods: We over-expressed both EWS/WT1 variants in murine embryonic fibroblasts (MEFs) of wild-type, p53(+/-) and p53(-/-) backgrounds and measured effects on cell-proliferation, anchorage-independent growth, clonogenicity after serum withdrawal, and sensitivity to cytotoxic drugs and gamma irradiation in comparison to control cells. We examined gene expression profiles in cells expressing EWS/WT1. Finally we validated our key findings in a small series of DSRCT. Results: Neither isoform of EWS/WT1 was sufficient to transform wild-type MEFs however the oncogenic potential of both was unmasked by p53 loss. Expression of EWS/WT1 in MEFs lacking at least one allele of p53 enhanced cell-proliferation, clonogenic survival and anchorage-independent growth. EWS/WT1 expression in wild-type MEFs conferred resistance to cell-cycle arrest after irradiation and daunorubicin induced apoptosis. We show DSRCT commonly have nuclear localization of p53, and copy-number amplification of MDM2/MDMX. Expression of either isoform of EWS/WT1 induced characteristic mRNA expression profiles. Gene-set enrichment analysis demonstrated enrichment of WNT pathway signatures in MEFs expressing EWS/WT1 + KTS. Wnt-activation was validated in cell lines with over-expression of EWS/WT1 and in DSRCT. Conclusion: In conclusion, we show both isoforms of EWS/WT1 have oncogenic potential in MEFs with loss of p53. In addition we provide the first link between EWS/WT1 and Wnt-pathway signaling. These data provide novel insights into the function of the EWS/WT1 fusion protein which characterize DSRCT. C1 [Bandopadhayay, Pratiti] Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. [Bandopadhayay, Pratiti] Boston Childrens Hosp, Boston, MA USA. [Jabbour, Anissa M.; Riffkin, Christopher; Salmanidis, Marika; Ekert, Paul G.] Univ Melbourne, Melbourne, Vic 3052, Australia. [Jabbour, Anissa M.; Riffkin, Christopher; Salmanidis, Marika; Ekert, Paul G.] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia. [Gordon, Lavinia; Popovski, Dean; Rigby, Lin; Ekert, Paul G.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia. [Ashley, David M.] Deakin Univ, Dept Med, Geelong, Vic 3220, Australia. [Watkins, David N.; Algar, Elizabeth] Monash Univ, Monash Inst Med Res, Clayton, Vic 3168, Australia. [Thomas, David M.] Univ Melbourne, Sir Peter MacCallum Dept Oncol, East Melbourne, Vic 3002, Australia. [Thomas, David M.] Peter MacCallum Canc Ctr, East Melbourne, Vic 3002, Australia. RP Ekert, PG (reprint author), Univ Melbourne, Melbourne, Vic 3052, Australia. EM Ekert@wehi.edu.au RI Ekert, Paul/Q-1842-2015; OI Ekert, Paul/0000-0002-2976-8617; Jabbour, Anissa/0000-0002-2540-0372 FU National Health and Medical Research Council (NHMRC) FX PB was supported by a National Health and Medical Research Council (NHMRC) Medical and Dental Postgraduate scholarship. NR 38 TC 4 Z9 4 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD DEC 9 PY 2013 VL 13 AR 585 DI 10.1186/1471-2407-13-585 PG 14 WC Oncology SC Oncology GA 280MQ UT WOS:000329034900002 PM 24321497 ER PT J AU Destaing, O Ferguson, SM Grichine, A Oddou, C De Camilli, P Albiges-Rizo, C Baron, R AF Destaing, Olivier Ferguson, Shawn M. Grichine, Alexei Oddou, Christiane De Camilli, Pietro Albiges-Rizo, Corinne Baron, Roland TI Essential Function of Dynamin in the Invasive Properties and Actin Architecture of v-Src Induced Podosomes/Invadosomes SO PLOS ONE LA English DT Article ID CLATHRIN-MEDIATED ENDOCYTOSIS; REGULATES PODOSOMES; FLUORESCENT PROTEIN; CRYSTAL-STRUCTURE; GTPASE ACTIVITY; BAR PROTEINS; SEALING ZONE; COATED PITS; N-WASP; CYTOSKELETON AB The large GTPase dynamin plays a key role in endocytosis but is also localized at numerous actin rich sites. We investigated dynamin functions at podosomes/invadosomes, actin-based cellular adhesion structures implicated in tissue invasion. Podosomes/invadosomes are constituted of long F-actin bundles perpendicular to the substratum (actin cores), connected to randomly arranged F-actin fibers parallel to the substratum (actin cloud). We show here that dynamin depletion in v-Src-transformed fibroblasts triggers a massive disorganization of podosomes/invadosomes (isolated or in rosettes), with a corresponding inhibition of their invasive properties. The action of dynamin at podosomes/invadosomes requires a functional full-length protein, suggesting that the effects of dynamin at these sites and in membrane remodelling during endocytosis are mediated by similar mechanisms. In order to determine direct effect of dynamin depletion on invadosome, an optogenetic approach based on the photosensitizer KillerRed was developed. Acute dynamin photo-inactivation leads to a very rapid disorganization of invadosome without affecting focal adhesions. Dynamin therefore is a key regulator of the architecture of actin in podosomes/invadosomes. C1 [Destaing, Olivier; Grichine, Alexei; Oddou, Christiane; Albiges-Rizo, Corinne] Univ Grenoble 1, Inst Albert Bonniot, Grenoble, France. [Destaing, Olivier; Ferguson, Shawn M.; De Camilli, Pietro] Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Cell Biol,Program Cellular Neurosci Neurodeg, New Haven, CT 06510 USA. [Baron, Roland] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Endocrine Unit, Boston, MA USA. [De Camilli, Pietro; Albiges-Rizo, Corinne; Baron, Roland] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Destaing, O (reprint author), Univ Grenoble 1, Inst Albert Bonniot, Univ Joseph Fourier Site Sante, Grenoble, France. EM olivier.destaing@ujf-grenoble.fr RI Albiges-Rizo, Corinne/M-2568-2013; destaing, olivier/M-3802-2013; Grichine, Alexei/M-3923-2013 FU National Institutes of Health [DE-04724, AR-42927, N536251, CA46128, DK45735, DA018343]; G. Harold and Leila Y. Mathers Charitable Foundation; Ligue Nationale Contre le Cancer (Equipe labellisee); fond d'intervention du Pole Chimie Sciences du Vivant; J. Fourier-Grenoble university; LLNC as "Equipe labellisee Ligue" FX The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This study was supported in part by National Institutes of Health grants DE-04724 and AR-42927 (to R B), by the G. Harold and Leila Y. Mathers Charitable Foundation, National Institutes of Health grants to P.D.C. (N536251, CA46128, DK45735, and DA018343), by the Ligue Nationale Contre le Cancer (Equipe labellisee-2010) and by the "fond d'intervention du Pole Chimie Sciences du Vivant", from J. Fourier-Grenoble university. The French team is supported by LLNC as "Equipe labellisee Ligue 2010". NR 67 TC 9 Z9 9 U1 0 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 9 PY 2013 VL 8 IS 12 AR e77956 DI 10.1371/journal.pone.0077956 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 275VD UT WOS:000328705200004 PM 24348990 ER PT J AU Gao, SL Li, AM Liu, FY Chen, FS Williams, M Zhang, CL Kelley, Z Wu, CL Luo, RC Xiao, H AF Gao, Shenglan Li, Aimin Liu, Feiye Chen, Fengsheng Williams, Mark Zhang, Chengliang Kelley, Zakiya Wu, Chin-Lee Luo, Rongcheng Xiao, Hua TI NCOA5 Haploinsufficiency Results in Glucose Intolerance and Subsequent Hepatocellular Carcinoma SO CANCER CELL LA English DT Article ID NF-KAPPA-B; INTERLEUKIN-6 GENE-EXPRESSION; INSULIN-RESISTANCE; ESTROGEN-RECEPTOR; DIABETES-MELLITUS; LIVER INFLAMMATION; ANDROGEN RECEPTOR; CANCER; CARCINOGENESIS; ASSOCIATION AB Type 2 diabetes (T2D) and male gender are associated with hepatocellular carcinoma (HCC) development. We demonstrate that heterozygous deletion of the Ncoa5 gene causes spontaneous development of HCC exclusively in male mice. Tumor development is preceded by increased interleukin-6 (IL-6) expression, early-onset glucose intolerance, and progressive steatosis and dysplasia in livers. Blockading IL-6 overexpression averts glucose intolerance and partially deters HCC development. Moreover, reduced NCOA5 expression is associated with a fraction of human HCCs and HCCs with comorbid T2D. These findings suggest that NCOA5 is a haploinsufficient tumor suppressor and that NCOA5 deficiency increases susceptibility to both glucose intolerance and HCC, partially by increasing IL-6 expression. Thus, our findings open additional avenues for developing therapeutic approaches to combat these diseases. C1 [Gao, Shenglan; Li, Aimin; Chen, Fengsheng; Williams, Mark; Zhang, Chengliang; Kelley, Zakiya; Xiao, Hua] Michigan State Univ, Dept Physiol, E Lansing, MI 48824 USA. [Gao, Shenglan] Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. [Williams, Mark] Michigan State Univ, Cell & Mol Biol Program, E Lansing, MI 48824 USA. [Li, Aimin; Liu, Feiye; Chen, Fengsheng; Luo, Rongcheng] Southern Med Univ, Nanfang Hosp, Ctr Canc, Guangzhou 510515, Guangdong, Peoples R China. [Wu, Chin-Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Luo, RC (reprint author), Southern Med Univ, Nanfang Hosp, Ctr Canc, Guangzhou 510515, Guangdong, Peoples R China. EM luorc01@163.com; xiaoh@msu.edu RI Zhang, Chengliang /E-6943-2016 OI Zhang, Chengliang /0000-0003-3798-4157 FU American Cancer Society Research Scholar Grant for Beginning Investigators [RSG0216501GMC]; National Cancer Institute grant [1R21CA158539] FX We thank Jill Pecha for the construction of Ncoa5 targeting vector, Chao Jiang for initial screening of targeted ES clones, Ying Qin for histological analysis of the sections, Karl Olson for helpful suggestions, and Irene Warner and Mingang Wang for technical support. This work was supported by American Cancer Society Research Scholar Grant for Beginning Investigators (RSG0216501GMC) and National Cancer Institute grant 1R21CA158539 (to H.X.). NR 53 TC 8 Z9 10 U1 2 U2 28 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD DEC 9 PY 2013 VL 24 IS 6 BP 725 EP 737 DI 10.1016/j.ccr.2013.11.005 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 272EN UT WOS:000328443200007 PM 24332041 ER PT J AU Li, LJ Shen, C Nakamura, E Ando, K Signoretti, S Beroukhim, R Cowley, GS Lizotte, P Liberzon, E Bair, S Root, DE Tamayo, P Tsherniak, A Cheng, SC Tabak, B Jacobsen, A Hakimi, AA Schultz, N Ciriello, G Sander, C Hsieh, JJ Kaelin, WG AF Li, Lianjie Shen, Chuan Nakamura, Eijiro Ando, Kiyohiro Signoretti, Sabina Beroukhim, Rameen Cowley, Glenn S. Lizotte, Patrick Liberzon, Ella Bair, Steven Root, David E. Tamayo, Pablo Tsherniak, Aviad Cheng, Su-Chun Tabak, Barbara Jacobsen, Anders Hakimi, A. Ari Schultz, Nikolaus Ciriello, Giovanni Sander, Chris Hsieh, James J. Kaelin, William G., Jr. TI SQSTM1 Is a Pathogenic Target of 5q Copy Number Gains in Kidney Cancer SO CANCER CELL LA English DT Article ID RENAL-CELL CARCINOMA; TUMOR-SUPPRESSOR PROTEIN; TRANSCRIPTION FACTOR NRF2; LINDAU GENE-PRODUCT; PROLYL HYDROXYLASE; P62/SEQUESTOSOME 1; OXIDATIVE STRESS; BETA-DOMAIN; P62; AUTOPHAGY AB Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer and is often linked to loss of chromosome 3p, which harbors the VHL tumor suppressor gene, loss of chromosome 14q, which includes HIF1A, and gain of chromosome 5q. The relevant target(s) on chromosome 5q is not known. Here, we show that 5q amplification leads to overexpression of the SQSTM1 oncogene in ccRCC lines and tumors. Overexpression of SQSTM1 in ccRCC lines promoted resistance to redox stress and increased soft agar growth, while downregulation of SQSTM1 decreased resistance to redox stress, impaired cellular fitness, and decreased tumor formation. Therefore, the selection pressure to amplify 5q in ccRCC is driven, at least partly, by SQSTM1. C1 [Li, Lianjie; Shen, Chuan; Nakamura, Eijiro; Ando, Kiyohiro; Signoretti, Sabina; Beroukhim, Rameen; Liberzon, Ella; Bair, Steven; Kaelin, William G., Jr.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Li, Lianjie; Shen, Chuan; Nakamura, Eijiro; Ando, Kiyohiro; Signoretti, Sabina; Beroukhim, Rameen; Liberzon, Ella; Bair, Steven; Tabak, Barbara; Kaelin, William G., Jr.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Beroukhim, Rameen; Tabak, Barbara] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Signoretti, Sabina] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Beroukhim, Rameen; Kaelin, William G., Jr.] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Beroukhim, Rameen; Cowley, Glenn S.; Lizotte, Patrick; Root, David E.; Tamayo, Pablo; Tsherniak, Aviad; Tabak, Barbara; Kaelin, William G., Jr.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Cheng, Su-Chun] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Jacobsen, Anders; Schultz, Nikolaus; Ciriello, Giovanni; Sander, Chris] Mem Sloan Kettering Canc Ctr, Dept Computat Biol, New York, NY USA. [Hakimi, A. Ari] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY USA. [Hsieh, James J.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY USA. [Hsieh, James J.] Mem Sloan Kettering Canc Ctr, Dept Human Oncol, New York, NY USA. [Hsieh, James J.] Mem Sloan Kettering Canc Ctr, Pathogenesis Program, New York, NY USA. [Liberzon, Ella; Kaelin, William G., Jr.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM william_kaelin@dfci.harvard.edu RI Jacobsen, Anders/K-1081-2013; OI Jacobsen, Anders/0000-0001-6847-4980; Schultz, Nikolaus/0000-0002-0131-4904; Lizotte, Patrick/0000-0001-9510-0036 FU National Institutes of Health FX We thank members of the W.G.K. laboratory for useful comments and Drs. Eileen White and David M. Sabatini for reagents. W.G.K. is a Howard Hughes Medical Institute investigator and supported by grants from the National Institutes of Health. NR 68 TC 30 Z9 30 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD DEC 9 PY 2013 VL 24 IS 6 BP 738 EP 750 DI 10.1016/j.ccr.2013.10.025 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 272EN UT WOS:000328443200008 PM 24332042 ER PT J AU Perets, R Wyant, GA Muto, KW Bijron, JG Poole, BB Chin, KT Chen, JYH Ohman, AW Stepule, CD Kwak, S Karst, AM Hirsch, MS Setlur, SR Crum, CP Dinulescu, DM Drapkin, R AF Perets, Ruth Wyant, Gregory A. Muto, Katherine W. Bijron, Jonathan G. Poole, Barish B. Chin, Kenneth T. Chen, Jin Yun H. Ohman, Anders W. Stepule, Corey D. Kwak, Soongu Karst, Alison M. Hirsch, Michelle S. Setlur, Sunita R. Crum, Christopher P. Dinulescu, Daniela M. Drapkin, Ronny TI Transformation of the Fallopian Tube Secretory Epithelium Leads to High-Grade Serous Ovarian Cancer in Brca;Tp53;Pten Models SO CANCER CELL LA English DT Article ID MOUSE-MODEL; CONDITIONAL INACTIVATION; SURFACE EPITHELIUM; CANDIDATE PRECURSOR; TUMOR-SUPPRESSOR; P53 MUTATIONS; CARCINOMA; BRCA1; PTEN; EXPRESSION AB High-grade serous ovarian carcinoma presents significant clinical and therapeutic challenges. Although the traditional model of carcinogenesis has focused on the ovary as a tumor initiation site, recent studies suggest that there may be additional sites of origin outside the ovary, namely the secretory cells of the fallopian tube. Our study demonstrates that high-grade serous tumors can originate in fallopian tubal secretory epithelial cells and also establishes serous tubal intraepithelial carcinoma as the precursor lesion to high-grade serous ovarian and peritoneal carcinomas in animal models targeting the Brca, Tp53, and Pten genes. These findings offer an avenue to address clinically important questions that are critical for cancer prevention and early detection in women carrying BRCA1 and BRCA2 mutations. C1 [Perets, Ruth; Kwak, Soongu; Karst, Alison M.; Drapkin, Ronny] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Wyant, Gregory A.; Muto, Katherine W.; Poole, Barish B.; Chin, Kenneth T.; Chen, Jin Yun H.; Ohman, Anders W.; Stepule, Corey D.; Setlur, Sunita R.; Dinulescu, Daniela M.] Harvard Univ, Sch Med, Dept Pathol, Eugene Braunwald Res Ctr, Boston, MA 02115 USA. [Bijron, Jonathan G.; Hirsch, Michelle S.; Crum, Christopher P.; Dinulescu, Daniela M.; Drapkin, Ronny] Harvard Univ, Sch Med, Dept Pathol, Div Womens & Perinatal Pathol,Brigham & Womens Ho, Boston, MA 02115 USA. RP Dinulescu, DM (reprint author), Harvard Univ, Sch Med, Dept Pathol, Eugene Braunwald Res Ctr, Boston, MA 02115 USA. EM ddinulescu@rics.bwh.harvard.edu; ronny_drapkin@dfci.harvard.edu RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 FU National Institutes of Health; SPORE [P50 CA105009]; EDRN [U01 CA152990, R21 CA156021]; DOD OCRP [W81XWH-10-1-0263]; American Cancer Society [RSG-13-083-01-TBG]; Ovarian Cycle and Ovarian Cancer Research Fund Liz Tilberis award; Burroughs-Wellcome Fund Career Award in the Biomedical Sciences [1005320.01]; V Foundation for Cancer Research Scholar Award; Marsha Rivkin Foundation for Ovarian Cancer Research; Mildred Moorman Ovarian Cancer Research Fund; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; Ovarian Cancer Research Fund Ann Schreiber award; National Ovarian Cancer Coalition; Mary Kay Foundation; Sandy Rollman Ovarian Cancer Foundation; Susan Smith Center for Women's Cancers at the Dana-Farber Cancer Institute; Debra and Robert First Fund; Gamel Family Fund; Eleanor and Miles Shore 50th Anniversary Fellowship Program for Scholars in Medicine Award FX The authors wish to thank Christine Lam, Mel Zheng, and Huiying Piao for excellent technical assistance and the members of the Dinulescu and Drapkin labs for helpful discussions. We thank Dr. Andrew Godwin (University of Kansas Medical Center) for the HIO cells. This work is supported by grants from the National Institutes of Health, SPORE P50 CA105009 (to R.D.), EDRN U01 CA152990 (to R.D.), R21 CA156021 (to RD.), DOD OCRP W81XWH-10-1-0263 award (to D.M.D.), American Cancer Society RSG-13-083-01-TBG award (to D.M.D.), Ovarian Cycle and Ovarian Cancer Research Fund Liz Tilberis award (to D.M.D.), Burroughs-Wellcome Fund Career Award in the Biomedical Sciences 1005320.01 (to D.M.D.), V Foundation for Cancer Research Scholar Award (to D.M.D.), Marsha Rivkin Foundation for Ovarian Cancer Research (to D.M.D.), the Mildred Moorman Ovarian Cancer Research Fund (to D.M.D.), the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to R.D.), Ovarian Cancer Research Fund Ann Schreiber award (to R.P.), the National Ovarian Cancer Coalition (to R.D. and R.P.), the Mary Kay Foundation (to R.D. and D.M.D.), Sandy Rollman Ovarian Cancer Foundation (to R.D.), the Susan Smith Center for Women's Cancers at the Dana-Farber Cancer Institute (to R.D. and D.M.D.), the Debra and Robert First Fund (to R.D.), the Gamel Family Fund (to RD.), and the Eleanor and Miles Shore 50th Anniversary Fellowship Program for Scholars in Medicine Award (to S.R.S.). NR 54 TC 117 Z9 118 U1 0 U2 19 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD DEC 9 PY 2013 VL 24 IS 6 BP 751 EP 765 DI 10.1016/j.ccr.2013.10.013 PG 15 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 272EN UT WOS:000328443200009 PM 24332043 ER PT J AU Chapuy, B McKeown, MR Lin, CY Monti, S Roemer, MGM Qi, J Rahl, PB Sun, HH Yeda, KT Doench, JG Reichert, E Kung, AL Rodig, SJ Young, RA Shipp, MA Bradner, JE AF Chapuy, Bjoern McKeown, Michael R. Lin, Charles Y. Monti, Stefano Roemer, Margaretha G. M. Qi, Jun Rahl, Peter B. Sun, Heather H. Yeda, Kelly T. Doench, John G. Reichert, Elaine Kung, Andrew L. Rodig, Scott J. Young, Richard A. Shipp, Margaret A. Bradner, James E. TI Discovery and Characterization of Super-Enhancer-Associated Dependencies in Diffuse Large B Cell Lymphoma SO CANCER CELL LA English DT Article ID BET BROMODOMAIN INHIBITION; OCA-B; SELECTIVE-INHIBITION; GENE-EXPRESSION; P-TEFB; C-MYC; TRANSCRIPTION; LEUKEMIA; BRD4; CHROMATIN AB Diffuse large B cell lymphoma (DLBCL) is a biologically heterogeneous and clinically aggressive disease. Here, we explore the role of bromodomain and extra-terminal domain (BET) proteins in DLBCL, using integrative chemical genetics and functional epigenomics. We observe highly asymmetric loading of bromodomain 4 (BRD4) at enhancers, with approximately 33% of all BRD4 localizing to enhancers at 1.6% of occupied genes. These super-enhancers prove particularly sensitive to bromodomain inhibition, explaining the selective effect of BET inhibitors on oncogenic and lineage-specific transcriptional circuits. Functional study of genes marked by super-enhancers identifies DLBCLs dependent on OCA-B and suggests a strategy for discovering unrecognized cancer dependencies. Translational studies performed on a comprehensive panel of DLBCLs establish a therapeutic rationale for evaluating BET inhibitors in this disease. C1 [Chapuy, Bjoern; McKeown, Michael R.; Lin, Charles Y.; Roemer, Margaretha G. M.; Qi, Jun; Yeda, Kelly T.; Reichert, Elaine; Shipp, Margaret A.; Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Monti, Stefano] Boston Univ, Sch Med, Sect Computat Biomed, Boston, MA 02118 USA. [Rahl, Peter B.; Young, Richard A.] MIT, Whitehead Inst Genome Res, Cambridge, MA 02142 USA. [Sun, Heather H.; Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Doench, John G.] Broad Inst, Cambridge, MA 02142 USA. [Kung, Andrew L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. RP Shipp, MA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM margaret_shipp@dfci.harvard.edu; james_bradner@dfci.harvard.edu OI Kung, Andrew/0000-0002-9091-488X; Doench, John/0000-0002-3707-9889 FU National Institutes of Health; Leukemia & Lymphoma Society; Damon-Runyon Cancer Research Foundation; Broad New Idea Award; William Lawrence and Blanche Hughes Foundation; American Society of Hematology; Department of Defense [CDMRP CA120184]; American Cancer Society [PF-11-042-01-DMC]; German Research Foundation [DFG Ch 735/1-1]; Syros Pharmaceuticals FX The authors acknowledge support from the National Institutes of Health and the Leukemia & Lymphoma Society (to M.A.S. and J.E.B.); the Damon-Runyon Cancer Research Foundation, the Broad New Idea Award, the William Lawrence and Blanche Hughes Foundation; and the American Society of Hematology (to J.E.B.); the Department of Defense (CDMRP CA120184 to C.Y.L.); the American Cancer Society (PF-11-042-01-DMC to P.B.R.); and the German Research Foundation (DFG Ch 735/1-1 to B.C.). Drug-like derivities of JQ1 have been licensed to Tensha Therapuetics for clinical development by DFCI. J.E.B. is a Scientific Founder of Tensha. J.E.B. and R.A.Y. are Scientific Founders of Syros Pharmacueticals. C.Y.L. and P.B.R. were paid consultants for Syros Pharmaceuticals. NR 51 TC 156 Z9 157 U1 6 U2 16 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD DEC 9 PY 2013 VL 24 IS 6 BP 777 EP 790 DI 10.1016/j.ccr.2013.11.003 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 272EN UT WOS:000328443200011 PM 24332044 ER PT J AU Shen, L Shah, BR Reyes, EM Thomas, L Wojdyla, D Diem, P Leiter, LA Charbonnel, B Mareev, V Horton, ES Haffner, SM Soska, V Holman, R Bethel, MA Schaper, F Sun, JL McMurray, JJV Califf, RM Krum, H AF Shen, Lan Shah, Bimal R. Reyes, Eric M. Thomas, Laine Wojdyla, Daniel Diem, Peter Leiter, Lawrence A. Charbonnel, Bernard Mareev, Viacheslav Horton, Edward S. Haffner, Steven M. Soska, Vladimir Holman, Rury Bethel, M. Angelyn Schaper, Frank Sun, Jie-Lena McMurray, John J. V. Califf, Robert M. Krum, Henry TI Role of diuretics, beta blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Article ID LIPID-LOWERING TREATMENT; ATTACK TRIAL ALLHAT; HIGH BLOOD-PRESSURE; CARDIOVASCULAR EVENTS; RANDOMIZED-TRIAL; ANTIHYPERTENSIVE DRUGS; PRIMARY PREVENTION; MELLITUS; THERAPY; HYPERTENSION AB Objective To examine the degree to which use of beta blockers, statins, and diuretics in patients with impaired glucose tolerance and other cardiovascular risk factors is associated with new onset diabetes. Design Reanalysis of data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial. Setting NAVIGATOR trial. Participants Patients who at baseline (enrolment) were treatment naive to beta blockers (n=5640), diuretics (n=6346), statins (n=6146), and calcium channel blockers (n=6294). Use of calcium channel blocker was used as a metabolically neutral control. Main outcome measures Development of new onset diabetes diagnosed by standard plasma glucose level in all participants and confirmed with glucose tolerance testing within 12 weeks after the increased glucose value was recorded. The relation between each treatment and new onset diabetes was evaluated using marginal structural models for causal inference, to account for time dependent confounding in treatment assignment. Results During the median five years of follow-up, beta blockers were started in 915 (16.2%) patients, diuretics in 1316 (20.7%), statins in 1353 (22.0%), and calcium channel blockers in 1171 (18.6%). After adjusting for baseline characteristics and time varying confounders, diuretics and statins were both associated with an increased risk of new onset diabetes (hazard ratio 1.23, 95% confidence interval 1.06 to 1.44, and 1.32, 1.14 to 1.48, respectively), whereas beta blockers and calcium channel blockers were not associated with new onset diabetes (1.10, 0.92 to 1.31, and 0.95, 0.79 to 1.13, respectively). Conclusions Among people with impaired glucose tolerance and other cardiovascular risk factors and with serial glucose measurements, diuretics and statins were associated with an increased risk of new onset diabetes, whereas the effect of beta blockers was non-significant. C1 [Shen, Lan; Shah, Bimal R.; Reyes, Eric M.; Thomas, Laine; Wojdyla, Daniel; Sun, Jie-Lena; Califf, Robert M.] Duke Clin Res Inst, Durham, NC USA. [Shen, Lan] Shanghai Jiao Tong Univ, Shanghai Renji Hosp, Dept Cardiol, Shanghai 200030, Peoples R China. [Diem, Peter] Univ Bern, Univ Hosp, Dept Endocrinol Diabet & Clin Nutr, CH-3012 Bern, Switzerland. [Leiter, Lawrence A.] St Michaels Hosp, Toronto, ON M5B 1W8, Canada. [Charbonnel, Bernard] Univ Hosp, Dept Endocrinol, Nantes, France. [Mareev, Viacheslav] Moscow MV Lomonosov State Univ, Moscow, Russia. [Horton, Edward S.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Haffner, Steven M.; Bethel, M. Angelyn] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Diabet Trials Unit, Oxford, England. [Soska, Vladimir] Masaryk Univ, Clin Internal Med 2, Brno, Czech Republic. [Soska, Vladimir] Masaryk Univ, Fac Med, Dept Biochem, Brno, Czech Republic. [Holman, Rury] Churchill Hosp, Oxford OX3 7LJ, England. [Schaper, Frank] Tech Univ Dresden, Ctr Clin Studies Metab & Endocrinol Knowledge & T, Dresden, Germany. [McMurray, John J. V.] Univ Glasgow, British Heart Fdn, Cardiovasc Res Ctr, Glasgow G12 8QQ, Lanark, Scotland. [Krum, Henry] Monash Univ, Alfred Hosp, Sch Publ Hlth & Prevent Med, Monash Ctr Cardiovasc Res & Educ Therapeut, Melbourne, Vic 3004, Australia. RP Krum, H (reprint author), Monash Univ, Alfred Hosp, Sch Publ Hlth & Prevent Med, Monash Ctr Cardiovasc Res & Educ Therapeut, Melbourne, Vic 3004, Australia. EM henry.krum@monash.edu OI Mareev, Vyacheslav Yurievich/0000-0002-7285-2048 NR 29 TC 21 Z9 25 U1 0 U2 16 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BMJ-BRIT MED J JI BMJ-British Medical Journal PD DEC 9 PY 2013 VL 347 AR f6745 DI 10.1136/bmj.f6745 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 273ZI UT WOS:000328574400002 PM 24322398 ER PT J AU Neophytou, AM Hart, JE Cavallari, JM Smith, TJ Dockery, DW Coull, BA Garshick, E Laden, F AF Neophytou, Andreas M. Hart, Jaime E. Cavallari, Jennifer M. Smith, Thomas J. Dockery, Douglas W. Coull, Brent A. Garshick, Eric Laden, Francine TI Traffic-related exposures and biomarkers of systemic inflammation, endothelial activation and oxidative stress: a panel study in the US trucking industry SO ENVIRONMENTAL HEALTH LA English DT Article DE Particulate matter; Elemental carbon; Organic carbon; ICAM-1; VCAM-1; IL-6; CRP; Inflammation; Endothelial activation; Trucking industry ID PARTICULATE AIR-POLLUTION; CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; SHORT-TERM EXPOSURE; MYOCARDIAL-INFARCTION; URINARY 8-HYDROXY-2'-DEOXYGUANOSINE; VENTRICULAR-ARRHYTHMIAS; CARDIOVASCULAR-DISEASE; OCCUPATIONAL-EXPOSURE; ADHESION MOLECULE-1 AB Background: Experimental evidence suggests that inhaled particles from vehicle exhaust have systemic effects on inflammation, endothelial activation and oxidative stress. In the present study we assess the relationships of short-term exposures with inflammatory endothelial activation and oxidative stress biomarker levels in a population of trucking industry workers. Methods: Blood and urine samples were collected pre and post-shift, at the beginning and end of a workweek from 67 male non-smoking US trucking industry workers. Concurrent measurements of microenvironment concentrations of elemental and organic carbon (EC & OC), and fine particulate matter (PM2.5) combined with time activity patterns allowed for calculation of individual exposures. Associations between daily and first and last-day average levels of exposures and repeated measures of intercellular and vascular cell adhesion molecule-1 (ICAM-1 & VCAM-1), interleukin 6 (IL-6) and C-reactive protein (CRP) blood levels and urinary 8-Hydroxy-2'-Deoxyguanosine (8-OHdG) were assessed using linear mixed effects models for repeated measures. Results: There was a statistically significant association between first and last-day average PM2.5 and 8-OHdG (21% increase, 95% CI: 2, 42%) and first and last-day average OC and IL-6 levels (18% increase 95% CI: 1, 37%) per IQR in exposure. There were no significant findings associated with EC or associations suggesting acute cross-shift effects. Conclusion: Our findings suggest associations between weekly average exposures of PM2.5 on markers of oxidative stress and OC on IL-6 levels. C1 [Neophytou, Andreas M.; Hart, Jaime E.; Cavallari, Jennifer M.; Smith, Thomas J.; Dockery, Douglas W.; Laden, Francine] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program, Boston, MA 02115 USA. [Hart, Jaime E.; Garshick, Eric; Laden, Francine] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Hart, Jaime E.; Garshick, Eric; Laden, Francine] Harvard Univ, Sch Med, Boston, MA USA. [Cavallari, Jennifer M.] Univ Connecticut, Ctr Hlth, Div Occupat & Environm Med, Farmington, CT USA. [Coull, Brent A.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Garshick, Eric] VA Boston Healthcare Syst, West Roxbury, MA USA. RP Neophytou, AM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program, 665 Huntington Ave, Boston, MA 02115 USA. EM aneophyt@hsph.harvard.edu FU National Institute of Health/National Institute of Environmental Health Sciences [R01 ES016284, ES000002] FX We thank Junfeng (Jim) Zhang, Marina J. Canner, Miguel Craig, Monica Zigman and William Roache for their contributions in the study. The study was supported by the National Institute of Health/National Institute of Environmental Health Sciences grants R01 ES016284 and ES000002. NR 51 TC 15 Z9 15 U1 5 U2 25 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 7 PY 2013 VL 12 AR 105 DI 10.1186/1476-069X-12-105 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 297VV UT WOS:000330284100001 PM 24314116 ER PT J AU Gohil, VM Zhu, L Baker, CD Cracan, V Yaseen, A Jain, M Clish, CB Brookes, PS Bakovic, M Mootha, VK AF Gohil, Vishal M. Zhu, Lin Baker, Charli D. Cracan, Valentin Yaseen, Abbas Jain, Mohit Clish, Clary B. Brookes, Paul S. Bakovic, Marica Mootha, Vamsi K. TI Meclizine Inhibits Mitochondria! Respiration through Direct Targeting of Cytosolic Phosphoethanolamine Metabolism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Energy Metabolism; Metabolomics; Mitochondria; Phosphatidylethanolamine; Respiration; Meclizine; Phosphoethanolamine ID PHOSPHATIDYLETHANOLAMINE; ETHANOLAMINE; PHOSPHATIDYLSERINE; CARDIOLIPIN; DISEASE; CTP; PURIFICATION; PATHWAY; CELLS; ASSAY AB We recently identified meclizine, an over-the-counter drug, as an inhibitor of mitochondrial respiration. Curiously, meclizine blunted respiration in intact cells but not in isolated mitochondria, suggesting an unorthodox mechanism. Using a metabolic profiling approach, we now show that treatment with meclizine leads to a sharp elevation of cellular phosphoethanolamine, an intermediate in the ethanolamine branch of the Kennedy pathway of phosphatidylethanolamine biosynthesis. Metabolic labeling and in vitro enzyme assays confirmed direct inhibition of the cytosolic enzyme CTP:phosphoethanolamine cytidylyltransferase (PCYT2). Inhibition of PCYT2 by meclizine led to rapid accumulation of its substrate, phosphoethanolamine, which is itself an inhibitor of mitochondrial respiration. Our work identifies the first pharmacologic inhibitor of the Kennedy pathway, demonstrates that its biosynthetic intermediate is an endogenous inhibitor of respiration, and provides key mechanistic insights that may facilitate repurposing meclizine for disorders of energy metabolism. C1 [Gohil, Vishal M.; Cracan, Valentin; Yaseen, Abbas; Jain, Mohit; Mootha, Vamsi K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Mol Biol, Boston, MA 02114 USA. [Gohil, Vishal M.; Cracan, Valentin; Yaseen, Abbas; Jain, Mohit; Mootha, Vamsi K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Med, Boston, MA 02114 USA. [Gohil, Vishal M.; Cracan, Valentin; Jain, Mohit; Clish, Clary B.; Mootha, Vamsi K.] Broad Inst, Cambridge, MA 02142 USA. [Gohil, Vishal M.; Cracan, Valentin; Jain, Mohit; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Gohil, Vishal M.; Baker, Charli D.] Texas A&M Univ, Dept Biochem & Biophys, College Stn, TX 77843 USA. [Zhu, Lin; Bakovic, Marica] Univ Guelph, Dept Human Hlth & Nutr Sci, Guelph, ON N1G 2W1, Canada. [Brookes, Paul S.] Univ Rochester, Med Ctr, Dept Anesthesiol, Rochester, NY 14642 USA. RP Gohil, VM (reprint author), Texas A&M Univ, Dept Biochem & Biophys, ILSB Rm 2146A,301 Old Main Dr, College Stn, TX 77843 USA. EM vgohil@tamu.edu FU National Institutes of Health [5K08HL107451]; American Diabetes Association/Smith Family Foundation; Welch Foundation [A-1810]; Canadian Institutes of Health Research; Ontario President Research Excellence Award; Texas AM University FX This work was supported, in whole or in part, by National Institutes of Health Grant 5K08HL107451 (to M. J.). This work was also supported by a grant from the American Diabetes Association/Smith Family Foundation (to V. K. M.). V. K. M. and V. M. G. are listed as inventors on a patent application filed by the Massachusetts General Hospital.; Supported by Welch Foundation Grant A-1810 and discretionary funds from Texas A&M University.; Supported by grants from the Canadian Institutes of Health Research and Ontario President Research Excellence Award. NR 36 TC 8 Z9 8 U1 2 U2 12 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 6 PY 2013 VL 288 IS 49 BP 35387 EP 35395 DI 10.1074/jbc.M113.489237 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 291YA UT WOS:000329867600035 PM 24142790 ER PT J AU Dichgans, M Malik, R Konig, IR Rosand, J Clarke, R Gretarsdottir, S Mitchell, BD Erdmann, J Kathiresan, S McPherson, R Sudlow, C Reilly, MP Thompson, JR Sharma, P Chambers, JC Watkins, H Rothwell, PM Roberts, R Markus, HS Samani, NJ Farrall, M Schunkert, H AF Dichgans, Martin Malik, Rainer Koenig, Inke R. Rosand, Jonathan Clarke, Robert Gretarsdottir, Solveig Mitchell, Braxton D. Erdmann, Jeanette Kathiresan, Sekar McPherson, Ruth Sudlow, Cathie Reilly, Muredach P. Thompson, John R. Sharma, Pankaj Chambers, John C. Watkins, Hugh Rothwell, Peter M. Roberts, Robert Markus, Hugh S. Samani, Nilesh J. Farrall, Martin Schunkert, Heribert TI Evidence for a shared genetic determination of Ischemic Stroke And Coronary Artery Disease - a genome-wide analysis SO CIRCULATION RESEARCH LA English DT Meeting Abstract CT Scientific Sessions of the American-Heart-Association CY NOV 16-20, 2013 CL Dallas, TX SP Amer Heart Assoc DE Genome-wide association studies (GWAS); Coronary artery disease; Stroke; Risk factors; Genetics C1 [Dichgans, Martin; Malik, Rainer] Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Rsch, Munich, Germany. [Koenig, Inke R.] Med Univ Lubeck, Inst Med Biometrie & Stat, D-23538 Lubeck, Germany. [Koenig, Inke R.] Univ Klinikum Schleswig Holstein, D-23538 Lubeck, Germany. [Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Rosand, Jonathan; Kathiresan, Sekar] Massachusetts Gen Hosp, Cntr Human Genet Rsch, Boston, MA 02114 USA. [Clarke, Robert] Univ Oxford, Clin Trial Serv Unit, Oxford, England. [Clarke, Robert] Univ Oxford, Epidemiol Studies Unit, Oxford, England. [Gretarsdottir, Solveig] DeCODE Genet, Reykjavik, Iceland. [Mitchell, Braxton D.] Univ Maryland, Sch Med, Dept Med, Rockville, MD USA. [Erdmann, Jeanette] Med Univ Lubeck, Inst Integrat & Expt Genom, D-23538 Lubeck, Germany. [McPherson, Ruth] Univ Ottawa, Inst Heart, Div Cardiol, Ottawa, ON, Canada. [Sudlow, Cathie] Univ Edinburgh, Div Clin Neurosci, Edinburgh, Midlothian, Scotland. [Reilly, Muredach P.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Thompson, John R.] Glenfield Hosp, Leicester NIHR Biomed Rsch Unit Cardiovasc Dis, Leicester, Leics, England. [Sharma, Pankaj] Univ London Imperial Coll Sci Technol & Med, London, England. [Sharma, Pankaj] Hammersmith Hosps, London, England. [Chambers, John C.] Univ London Imperial Coll Sci Technol & Med, Sch Med, London, England. [Watkins, Hugh] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA 02115 USA. [Rothwell, Peter M.] Univ Dept Clin Neurol, Radcliffe Infirm, Stroke Prevent Rsch Unit, Oxford, England. [Roberts, Robert] Univ Ottawa, John & Jennifer Ruddy Canadian Cardiovasc Genet C, Ottawa, ON, Canada. [Markus, Hugh S.] Kings Coll London, Sch Med & Dent, Dept Neurol, London, England. [Samani, Nilesh J.] Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England. [Farrall, Martin] Univ Oxford, Wellcome Trust Cntr Human Genet, Oxford, Egypt. [Schunkert, Heribert] German Heart Cntr Munich, Dept Cardiol, Munich, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 EI 1524-4571 J9 CIRC RES JI Circ.Res. PD DEC 6 PY 2013 VL 113 IS 12 BP E160 EP E161 PG 2 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 298VY UT WOS:000330353800020 ER PT J AU Fukaya, M Tamura, Y Chiba, Y Tanioka, T Mao, J Inoue, Y Yamada, M Waeber, C Ido-Kitamura, Y Kitamura, T Kaneki, M AF Fukaya, Makiko Tamura, Yoshiaki Chiba, Yuko Tanioka, Toshihiro Mao, Ji Inoue, Yoko Yamada, Marina Waeber, Christian Ido-Kitamura, Yukari Kitamura, Tadahiro Kaneki, Masao TI Protective effects of a nicotinamide derivative, isonicotinamide, against streptozotocin-induced beta-cell damage and diabetes in mice SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Pancreatic beta-cells; Diabetes; Isonicotinamide; Streptozotocin ID INTERVENTION TRIAL ENDIT; INSULIN-SECRETION; NOD MOUSE; SIRT1; ONSET; RESISTANCE; RISK; IDDM; PROGRESSION; INHIBITION AB Objective: Nicotinamide rescues beta-cell damage and diabetes in rodents, but a large-scale clinical trial failed to show the benefit of nicotinamide in the prevention of type 1 diabetes. Recent studies have shown that Sirt1 deacetylase, a putative protector of beta-cells, is inhibited by nicotinamide. We investigated the effects of isonicotinamide, which is a derivative of nicotinamide and does not inhibit Sirt1, on streptozotocin (STZ)-induced diabetes in mice. Research design and methods: Male C57BL/6 mice were administered with three different doses of STZ (65, 75, and 100 mg/kg BW) alone or in combination with subsequent high-fat feeding. The mice were treated with isonicotinamide (250 mg/kg BW/day) or phosphate-buffered saline for 10 days. The effects of isonicotinamide on STZ-induced diabetes were assessed by blood glucose levels, glucose tolerance test, and immunohistochemistry. Results: Isonicotinamide effectively prevented hyperglycemia induced by higher doses of STZ (75 and 100 mg/kg BW) alone and low-dose STZ (65 mg/kg BW) followed by 6-week high-fat diet in mice. The protective effects of isonicotinamide were associated with decreased apoptosis of beta-cells and reductions in both insulin content and insulin-positive area in the pancreas of STZ-administered mice. In addition, isonicotinamide inhibited STZ-induced apoptosis in cultured isolated islets. Conclusions: These data clearly demonstrate that isonicotinamide exerts anti-diabetogenic effects by preventing beta-cell damage after STZ administration. These findings warrant further investigations on the protective effects of isonicotinamide and related compounds against beta-cell damage in diabetes. (C) 2013 Elsevier Inc. All rights reserved. C1 [Fukaya, Makiko; Tamura, Yoshiaki; Chiba, Yuko; Tanioka, Toshihiro; Mao, Ji; Inoue, Yoko; Yamada, Marina; Kaneki, Masao] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med,Shriners Hos, Charlestown, MA 02129 USA. [Waeber, Christian] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. [Ido-Kitamura, Yukari; Kitamura, Tadahiro] Gunma Univ, Inst Mol & Cellular Regulat, Metab Signal Res Ctr, Gunma 3718512, Japan. RP Kaneki, M (reprint author), 149 13th St,Rm 6604, Charlestown, MA 02129 USA. EM mkaneki@helix.mgh.harvard.edu RI Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 FU National Institutes of Health [R01 DK05827, P30NS045776]; American Diabetes Association [7-08-RA-77] FX We thank Mr. M. Kobayashi and Ms. C. Osawa (Gunma University) for their superb technical assistance. This work was supported by research Grants to M.K. from the National Institutes of Health (R01 DK05827) and American Diabetes Association (7-08-RA-77), and to the Microscopy and Image Analysis Core of Massachusetts General Hospital (P30NS045776) from the National Institutes of Health. NR 35 TC 7 Z9 7 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 6 PY 2013 VL 442 IS 1-2 BP 92 EP 98 DI 10.1016/j.bbrc.2013.11.024 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 282CB UT WOS:000329146800016 PM 24246675 ER PT J AU Mishra, RK Dubin, RF AF Mishra, Rakesh K. Dubin, Ruth F. TI The Effects of Frequent Hemodialysis on Left Ventricular Mass, Volumes, and Geometry SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID STAGE RENAL-DISEASE; BLOOD-PRESSURE; NOCTURNAL HEMODIALYSIS; HYPERTROPHY; SURVIVAL; DIALYSIS; DETERMINANTS; REDUCTION; MECHANICS; FAILURE C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. [Mishra, Rakesh K.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Mishra, RK (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Box 111C, San Francisco, CA 94121 USA. EM rakesh.mishra@ucsf.edu FU NIDDK NIH HHS [T32 DK007219, K23 DK092354] NR 28 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD DEC 6 PY 2013 VL 8 IS 12 BP 2025 EP 2027 DI 10.2215/CJN.10611013 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 265KT UT WOS:000327951100001 PM 24235288 ER PT J AU Alge, JL Karakala, N Neely, BA Janech, MG Tumlin, JA Chawla, LS Shaw, AD Arthur, JM AF Alge, Joseph L. Karakala, Nithin Neely, Benjamin A. Janech, Michael G. Tumlin, James A. Chawla, Lakhmir S. Shaw, Andrew D. Arthur, John M. CA SAKInet Investigator TI Association of Elevated Urinary Concentration of Renin-Angiotensin System Components and Severe AKI SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE KIDNEY INJURY; ACUTE-RENAL-FAILURE; GELATINASE-ASSOCIATED LIPOCALIN; FACTOR-KAPPA-B; CARDIAC-SURGERY; HOSPITALIZED-PATIENTS; AT(2) RECEPTORS; RIFLE CRITERIA; BIOMARKER; RISK AB BackgroundPrognostic biomarkers that predict the severity of AKI at an early time point are needed. Urinary angiotensinogen was recently identified as a prognostic AKI biomarker. The study hypothesis is that urinary renin could also predict AKI severity and that in combination angiotensinogen and renin would be a strong predictor of prognosis at the time of AKI diagnosis.Design, setting, participants, & measurementsIn this multicenter, retrospective cohort study, urine was obtained from 204 patients who developed AKI after cardiac surgery from August 2008 to June 1, 2012. All patients were classified as having Acute Kidney Injury Network (AKIN) stage 1 disease by serum creatinine criteria at the time of sample collection. Urine output was not used for staging. Urinary angiotensinogen and renin were measured, and the area under the receiver-operating characteristic curve (AUC) was used to test for prediction of progression to AKIN stage 3 or in-hospital 30-day mortality. These biomarkers were added stepwise to a clinical model, and improvement in prognostic predictive performance was evaluated by category free net reclassification improvement (cfNRI) and chi-squared automatic interaction detection (CHAID).ResultsBoth the urinary angiotensinogen-to-creatinine ratio (uAnCR; AUC, 0.75; 95% confidence interval [CI], 0.65 to 0.85) and the urinary renin-to-creatinine ratio (uRenCR; AUC, 0.70; 95% CI, 0.57 to 0.83) predicted AKIN stage 3 or death. Addition of uAnCR to a clinical model substantially improved prediction of the outcome (AUC, 0.85; cfNRI, 0.673), augmenting sensitivity and specificity. Further addition of uRenCR increased the sensitivity of the model (cfNRI(events), 0.44). CHAID produced a highly accurate model (AUC, 0.91) and identified the combination of uAnCR >337.89 ng/mg and uRenCR >893.41 pg/mg as the strongest predictors (positive predictive value, 80.4%; negative predictive value, 90.7%; accuracy, 90.2%).ConclusionThe combination of urinary angiotensinogen and renin predicts progression to very severe disease in patients with early AKI after cardiac surgery. C1 [Alge, Joseph L.; Karakala, Nithin; Neely, Benjamin A.; Janech, Michael G.; Arthur, John M.] Med Univ S Carolina, Charleston, SC 29425 USA. [Tumlin, James A.] Univ Tennessee, Coll Med Chattanooga, Chattanooga, TN USA. [Chawla, Lakhmir S.] George Washington Univ, Washington, DC USA. [Shaw, Andrew D.] Duke Univ, Durham, NC USA. [Shaw, Andrew D.] Durham Vet Affairs Med Ctr, Durham, NC USA. [Arthur, John M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Arthur, JM (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, 96 Jonathan Lucas St,POB 250623, Charleston, SC 29425 USA. EM arthurj@musc.edu RI Velez, Juan Carlos/N-3782-2016; OI Neely, Benjamin/0000-0001-6120-7695; Alge, Joseph/0000-0002-2491-1066; Janech, Michael/0000-0002-3202-4811 FU National Institutes of Health [R01 DK080234]; Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs FX This study was supported by National Institutes of Health grant R01 DK080234 and by a Merit Review award from the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs. The contents do not necessarily represent the views of the Department of Veterans Affairs or the United States government. NR 39 TC 12 Z9 13 U1 0 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD DEC 6 PY 2013 VL 8 IS 12 BP 2043 EP 2052 DI 10.2215/CJN.03510413 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 265KT UT WOS:000327951100005 PM 24009222 ER PT J AU Vardi, M Yeh, RW Herzog, CA Winkelmayer, WC Setoguchi, S Charytan, DM AF Vardi, Moshe Yeh, Robert W. Herzog, Charles A. Winkelmayer, Wolfgang C. Setoguchi, Soko Charytan, David M. TI Strategies for Postmarketing Surveillance of Drugs and Devices in Patients with ESRD Undergoing Dialysis SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CLUSTER RANDOMIZED-TRIALS; MEDICAL-PRODUCT-SAFETY; HEMODIALYSIS-PATIENTS; CLINICAL-TRIALS; PRIMARY-CARE; MORTALITY; DISEASE; MULTICENTER; VALIDATION; PACLITAXEL AB The lack of evidence on the effectiveness and safety of interventions in chronic dialysis patients has been a subject of continuing criticism. New technologies are often introduced into the market without having specifically studied or even included patients with advanced kidney disease. Therefore, the need to generate valid effectiveness and safety data in this vulnerable subpopulation is of utmost importance. The US Food and Drug Administration has recently placed an increased focus on safety surveillance, and sponsors must now meet this additional postmarketing commitment. In patients with ESRD, the unique data collection environment in the United States allows for creative and efficient study designs to meet the needs of patients, providers, and sponsors. The purpose of this manuscript is to review the methodological and practical aspects of the different options for postmarketing study design in this field, with critical appraisal of their advantages and disadvantages. C1 [Vardi, Moshe; Yeh, Robert W.; Charytan, David M.] Harvard Clin Res Inst, Boston, MA USA. [Yeh, Robert W.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Herzog, Charles A.] Univ Minnesota, Hennepin Cty Med Ctr, Dept Internal Med, Div Cardiol, Minneapolis, MN 55415 USA. [Winkelmayer, Wolfgang C.] Stanford Univ, Sch Med, Div Nephrol, Palo Alto, CA 94304 USA. [Setoguchi, Soko] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Charytan, David M.] Brigham & Womens Hosp, Div Renal, Boston, MA 02120 USA. [Charytan, David M.] Brigham & Womens Hosp, Boston, MA 02120 USA. RP Charytan, DM (reprint author), Brigham & Womens Hosp, Div Renal, 1620 Tremont St,3rd Floor, Boston, MA 02120 USA. EM dcharytan@partners.org FU Affymax; Amgen; Zoll; National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases; Johnson Johnson FX The authors consulted for the Harvard Clinical Research Institute and/or the Chronic Disease Research Group on the design of a postmarketing study for Affymax (Palo Alto, CA). In addition, the following individual disclosures are listed. M. V. and R.W.Y. have no disclosures. C. A. H. has consulted for Abbott, Affymax, Amgen, Fibrogen, Johnson & Johnson, Medtronic, and Merck; provided research support for Affymax, Amgen, and Zoll; received royalties from UpToDate; had equity interest Boston Scientific, Cambridge Heart, Johnson & Johnson, and Merck; served on the safety advisory board for Keryx; was a member of the Board of Trustees for Roche Foundation for Anemia Research; and provided research support for the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases. W. C. W. reports having served as a scientific advisor or member of adverse event adjudication committees for Amgen, Bayer, GlaxoSmithKline, Keryx, and Medtronic. S. S. reports receiving research support from Johnson & Johnson and honoraria for consulting from Affymax and Novartis. D. M. C has consulted for or contributed clinical trial design to Medtronic, Tengion, Keryx, and Affymax and has been on clinical events committees for PLC Medical. NR 50 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD DEC 6 PY 2013 VL 8 IS 12 BP 2213 EP 2220 DI 10.2215/CJN.05130513 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 265KT UT WOS:000327951100025 PM 23970129 ER PT J AU Bester, J Buys, AV Lipinski, B Kell, DB Pretorius, E AF Bester, Janette Buys, Antoinette V. Lipinski, Boguslaw Kell, Douglas B. Pretorius, Etheresia TI High ferritin levels have major effects on the morphology of erythrocytes in Alzheimer's disease SO FRONTIERS IN AGING NEUROSCIENCE LA English DT Article DE Alzheimer's disease; erythrocytes; iron; scanning electron microscopy; atomic force microscopy ID SCANNING-ELECTRON-MICROSCOPY; ATOMIC-FORCE MICROSCOPE; HEREDITARY HEMOCHROMATOSIS; IRON-OVERLOAD; OXIDATIVE STRESS; SERUM FERRITIN; CARDIOVASCULAR-DISEASE; COGNITIVE IMPAIRMENT; ASYMPTOMATIC SUBJECTS; SEDIMENTATION-RATE AB Introduction: Unliganded iron both contributes to the pathology of Alzheimer's disease (AD) and also changes the morphology of erythrocytes (RBCs). We tested the hypothesis that these two facts might be linked, i.e., that the RBCs of AD individuals have a variant morphology, that might have diagnostic or prognostic value. Methods: We included a literature survey of AD and its relationships to the vascular system, followed by a laboratory study. Four different microscopy techniques were used and results statistically compared to analyze trends between high and normal serum ferritin (SF) AD individuals. Results: Light and scanning electron microscopies showed little difference between the morphologies of RBCs taken from healthy individuals and from normal SF AD individuals. By contrast, there were substantial changes in the morphology of RBCs taken from high SF AD individuals. These differences were also observed using confocal microscopy and as a significantly greater membrane stiffness (measured using force-distance curves). Conclusion: We argue that high ferritin levels may contribute to an accelerated pathology in AD. Our findings reinforce the importance of (unliganded) iron in AD, and suggest the possibility both of an early diagnosis and some means of treating or slowing down the progress of this disease. C1 [Bester, Janette; Pretorius, Etheresia] Univ Pretoria, Fac Hlth Sci, Dept Physiol, ZA-0007 Arcadia, South Africa. [Buys, Antoinette V.] Univ Pretoria, Microscopy & Microanal Unit, Arcadia, South Africa. [Lipinski, Boguslaw] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Kell, Douglas B.] Univ Manchester, Sch Chem, Manchester M1 7DN, Lancs, England. [Kell, Douglas B.] Univ Manchester, Manchester Inst Biotechnol, Manchester M1 7DN, Lancs, England. RP Kell, DB (reprint author), Univ Manchester, Sch Chem, 131 Princess St, Manchester M1 7DN, Lancs, England. EM dbk@manchester.ac.uk; resia.pretorius@up.ac.za OI Pretorius, Etheresia/0000-0002-9108-2384; Kell, Douglas/0000-0001-5838-7963 FU The National Research Foundation of South Africa (NRF) FX Funding body: The National Research Foundation of South Africa (NRF): E Pretorius. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 124 TC 16 Z9 16 U1 7 U2 29 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1663-4365 J9 FRONT AGING NEUROSCI JI Front. Aging Neurosci. PD DEC 6 PY 2013 VL 5 AR UNSP 88 DI 10.3389/fnagi.2013.00088 PG 14 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 269TF UT WOS:000328264100002 PM 24367334 ER PT J AU Carreras, I Mckee, AC Choi, JK Aytan, N Kowall, NW Jenkins, BG Dedeoglu, A AF Carreras, Isabel McKee, Ann C. Choi, Ji-Kyung Aytan, Nurgul Kowall, Neil W. Jenkins, Bruce G. Dedeoglu, Alpaslan TI R-flurbiprofen improves tau, but not A beta pathology in a triple transgenic model of Alzheimer's disease SO BRAIN RESEARCH LA English DT Article DE R-flurbiprofen; Hyperphosphorylated tau; A beta; 3xTg-AD mice; Magnetic resonance spectroscopy ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; MAGNETIC-RESONANCE-SPECTROSCOPY; GAMMA-SECRETASE MODULATORS; IMPAIR SYNAPTIC PLASTICITY; IN-VIVO; MOUSE MODELS; ANIMAL-MODEL; HUNTINGTONS-DISEASE; AMYLOID DEPOSITION; MICE AB We have previously reported that chronic ibuprofen treatment improves cognition and decreases intracellular A beta and phosphorylated-tau levels in 3xTg-AD mice. Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) that independently of its anti-inflammatory effects has anti-amyloidogenic activity as a gamma-secretase modulator (GSM) and both activities have the potential to decrease A beta pathology. To further understand the effects of NSAIDs in 3xTg-AD mice, we treated 3xTg-AD mice with R-flurbiprofen, an enantiomer of the NSAID flurbiprofen that maintains the GSM activity but has greatly reduced anti-inflammatory activity, and analyzed its effect on cognition, A beta, tau, and the neurochemical profile of the hippocampus. Treatment with R-flurbiprofen from 5 to 7 months of age resulted in improved cognition on the radial arm water maze (RAWM) test and decreased the level of hyperphosphorylated tau immunostained with AT8 and PHF-1 antibodies. No significant changes in the level of A beta (using 6E10 and NU-1 antibodies) were detected. Using magnetic resonance spectroscopy (MRS) we found that R-flurbiprofen treatment decreased the elevated level of glutamine in 3xTg-AD mice down to the level detected in non-transgenic mice. Glutamine levels correlated with PHF-1 immunostained hyperphosphorylated tau. We also found an inverse correlation between the concentration of glutamate and learning across all the mice in the study. Glutamine and glutamate, neurochemicals that shuttles between neurons and astrocytes to maintain glutamate homeostasis in the synapses, deserve further attention as MR markers of cognitive function. Published by Elsevier B.V. C1 [Carreras, Isabel; McKee, Ann C.; Aytan, Nurgul; Kowall, Neil W.; Dedeoglu, Alpaslan] VA Boston Healthcare Syst, Res GRECC, Boston, MA 02130 USA. [Carreras, Isabel] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. [McKee, Ann C.; Aytan, Nurgul; Kowall, Neil W.; Dedeoglu, Alpaslan] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [McKee, Ann C.; Kowall, Neil W.] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. [Choi, Ji-Kyung; Jenkins, Bruce G.; Dedeoglu, Alpaslan] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Dept Radiol, Boston, MA 02114 USA. [Choi, Ji-Kyung; Jenkins, Bruce G.; Dedeoglu, Alpaslan] Harvard Univ, Sch Med, Boston, MA USA. RP Dedeoglu, A (reprint author), VA Boston Healthcare Syst, Res & Dev Serv, 150 S Huntington Ave,Bldg 1A-112, Boston, MA 02130 USA. EM dedeoglu@bu.edu RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 FU NIA [R01AG031896]; Department of Veteran Affairs; [CDA-2] FX This research is supported by Grants from NIA (R01AG031896) to A. Dedeoglu, the Department of Veteran Affairs (Merit Award) to A. Dedeoglu and CDA-2 to I. Carreras. There is no conflict of interest. The authors thank Dr. Peter Davies for the generous gift of the antibodies used in these studies, Dr. Frank LaFerla for providing the 3xTg-AD mice, Carol A. Kubilus for her technical help in immunohistochemistry, Lokman Hossain for animal husbandry, and Dr. Kenton H. Zavitz for providing the R-flurbiprofen (tarenflurbil) and measuring R-flurbiprofen in plasma and brain. NR 80 TC 8 Z9 10 U1 0 U2 11 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 6 PY 2013 VL 1541 BP 115 EP 127 DI 10.1016/j.brainres.2013.10.025 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 266GZ UT WOS:000328013400012 PM 24161403 ER PT J AU Bredeson, C LeRademacher, J Kato, K DiPersio, JF Agura, E Devine, SM Appelbaum, FR Tomblyn, MR Laport, GG Zhu, XC McCarthy, PL Ho, VT Cooke, KR Armstrong, E Smith, A Rizzo, JD Burkart, JM Pasquini, MC AF Bredeson, Christopher LeRademacher, Jennifer Kato, Kazunobu DiPersio, John F. Agura, Edward Devine, Steven M. Appelbaum, Frederick R. Tomblyn, Marcie R. Laport, Ginna G. Zhu, Xiaochun McCarthy, Philip L. Ho, Vincent T. Cooke, Kenneth R. Armstrong, Elizabeth Smith, Angela Rizzo, J. Douglas Burkart, Jeanne M. Pasquini, Marcelo C. TI Prospective cohort study comparing intravenous busulfan to total body irradiation in hematopoietic cell transplantation SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; DAILY IV-BUSULFAN; TERM-FOLLOW-UP; PLUS CYCLOPHOSPHAMIDE; RANDOMIZED-TRIAL; CONDITIONING THERAPY; PREPARATIVE REGIMEN; 100-DAY MORTALITY; GRAFT-REJECTION AB We conducted a prospective cohort study testing the noninferiority of survival of ablative intravenous busulfan (IV-BU) vs ablative total body irradiation (TBI)-based regimens in myeloid malignancies. A total of 1483 patients undergoing transplantation for myeloid malignancies (IV-BU, N = 1025; TBI, N = 458) were enrolled. Cohorts were similar with respect to age, gender, race, performance score, disease, and disease stage at transplantation. Most patients had acute myeloid leukemia (68% IV-BU, 78% TBI). Grafts were primarily peripheral blood (77%) from HLA-matched siblings (40%) or well-matched unrelated donors (48%). Two-year probabilities of survival (95% confidence interval [CI]), were 56% (95% CI, 53%-60%) and 48% (95% CI, 43%-54%, P = .019) for IV-BU (relative risk, 0.82; 95% CI, 0.68-0.98, P = .03) and TBI, respectively. Corresponding incidences of transplant-related mortality (TRM) were 18% (95% CI, 16%-21%) and 19% (95% CI, 15%-23%, P = .75) and disease progression were 34% (95% CI, 31%-37%) and 39% (95% CI, 34%-44%, P = .08). The incidence of hepatic veno-occlusive disease (VOD) was 5% for IV-BU and 1% with TBI (P < .001). There were no differences in progression-free survival and graft-versus-host disease. Compared with TBI, IV-BU resulted in superior survival with no increased risk for relapse or TRM. These results support the use of myeloablative IV-BU vs TBI-based conditioning regimens for treatment of myeloid malignancies. (Blood. 2013;122(24):3871-3878) C1 [Bredeson, Christopher] Univ Ottawa, Res Inst, Ottawa Hosp, Ottawa, ON, Canada. [LeRademacher, Jennifer; Zhu, Xiaochun; Rizzo, J. Douglas; Burkart, Jeanne M.; Pasquini, Marcelo C.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Kato, Kazunobu; Armstrong, Elizabeth; Smith, Angela] Otsuka Pharmaceut Dev & Commercializat Inc, Princeton, NJ USA. [DiPersio, John F.] Washington Univ, Sch Med, Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Agura, Edward] Baylor Univ, Med Ctr, Dallas, TX USA. [Devine, Steven M.] Ohio State Univ, Med Ctr, James Canc Ctr, Columbus, OH 43210 USA. [Appelbaum, Frederick R.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Tomblyn, Marcie R.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Laport, Ginna G.] Stanford Univ, Med Ctr, Div Blood & Marrow Transplantat, Stanford, CA 94305 USA. [McCarthy, Philip L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Ho, Vincent T.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Cooke, Kenneth R.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Pediat BMT Program, Baltimore, MD USA. RP Bredeson, C (reprint author), Blood Dis Ctr, L2265b,501 Smyth Rd, Ottawa, ON K1H 8L6, Canada. EM cbredeson@ohri.ca FU Otsuka Pharmaceutical Development and Commercialization, Inc; National Institutes of Health National Cancer Institute (NCI) [U24 CA076518]; National Heart, Lung, and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases; NHLBI [U10 HL069294]; NCI; Health Resources and Services Administration/US Department of Health and Human Services [HHSH250201200016C]; Office of Naval Research [N00014-12-1-0142, N00014-13-1-0039]; Allos Therapeutics, Inc; Amgen, Inc; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Celgene Corporation; Fresenius-Biotech North America, Inc; Gamida Cell Teva Joint Venture Ltd; Genentech, Inc; Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Histo-Genetics, Inc; Kiadis Pharma; Leukemia & Lymphoma Society; Medical College of Wisconsin; Merck Co, Inc; Millennium: The Takeda Oncology Co; Milliman USA, Inc; Miltenyi Biotec, Inc; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc; Osiris Therapeutics, Inc; Otsuka America Pharmaceutical, Inc; Remedy Informatics; Sanofi US; Seattle Genetics; Sigma-tau Pharmaceuticals; Soligenix, Inc; StemCyte, A Global Cord Blood Therapeutics Co; Stemsoft Software, Inc; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; TerumoBCT; Teva Neuroscience, Inc; THERAKOS, Inc; Wellpoint, Inc. FX The authors are thankful for the support by Otsuka Pharmaceutical Development and Commercialization, Inc, and for the participation of 120 centers in North and South America.; The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24 CA076518 from the National Institutes of Health National Cancer Institute (NCI); the National Heart, Lung, and Blood Institute (NHLBI); and the National Institute of Allergy and Infectious Diseases; Grant/Cooperative Agreement U10 HL069294 from NHLBI and NCI; contract HHSH250201200016C with the Health Resources and Services Administration/US Department of Health and Human Services; grants N00014-12-1-0142 and N00014-13-1-0039 from the Office of Naval Research; and grants from Allos Therapeutics, Inc; Amgen, Inc; Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Celgene Corporation; Fresenius-Biotech North America, Inc; Gamida Cell Teva Joint Venture Ltd; Genentech, Inc; Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Histo-Genetics, Inc; Kiadis Pharma; The Leukemia & Lymphoma Society; The Medical College of Wisconsin; Merck & Co, Inc; Millennium: The Takeda Oncology Co; Milliman USA, Inc; Miltenyi Biotec, Inc; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc; Osiris Therapeutics, Inc; Otsuka America Pharmaceutical, Inc; Remedy Informatics; Sanofi US; Seattle Genetics; Sigma-tau Pharmaceuticals; Soligenix, Inc; StemCyte, A Global Cord Blood Therapeutics Co; Stemsoft Software, Inc; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; TerumoBCT; Teva Neuroscience, Inc; THERAKOS, Inc; and Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the Department of Defense, or any other agency of the US Government. NR 26 TC 36 Z9 36 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 5 PY 2013 VL 122 IS 24 BP 3871 EP 3878 DI 10.1182/blood-2013-08-519009 PG 8 WC Hematology SC Hematology GA 290EV UT WOS:000329737600010 PM 24081656 ER PT J AU Stachura, DL Svoboda, O Campbell, CA Espin-Palazon, R Lau, RP Zon, LI Bartunek, P Traver, D AF Stachura, David L. Svoboda, Ondrej Campbell, Clyde A. Espin-Palazon, Raquel Lau, Ryan P. Zon, Leonard I. Bartunek, Petr Traver, David TI The zebrafish granulocyte colony-stimulating factors (Gcsfs): 2 paralogous cytokines and their roles in hematopoietic development and maintenance SO BLOOD LA English DT Article ID IN-VITRO DIFFERENTIATION; FACTOR-RECEPTOR; G-CSF; STEM-CELLS; PROGENITOR CELLS; GM-CSF; DEFINITIVE HEMATOPOIESIS; GROWTH-FACTOR; FACTOR GENES; EXPRESSION AB Granulocyte colony-stimulating factor (Gcsf) drives the proliferation and differentiation of granulocytes, monocytes, and macrophages (mws) from hematopoietic stem and progenitor cells (HSPCs). Analysis of the zebrafish genome indicates the presence of 2 Gcsf ligands, likely resulting from a duplication event in teleost evolution. Although Gcsfa and Gcsfb share low sequence conservation, they share significant similarity in their predicted ligand/receptor interaction sites and structure. Each ligand displays differential temporal expression patterns during embryogenesis and spatial expression patterns in adult animals. To determine the functions of each ligand, we performed loss-and gain-of-function experiments. Both ligands signal through the Gcsf receptor to expand primitive neutrophils and m phi s, as well as definitive granulocytes. To further address their functions, we generated recombinant versions and tested them in clonal progenitor assays. These sensitive in vitro techniques indicated similar functional attributes in supporting HSPC growth and differentiation. Finally, in addition to supporting myeloid differentiation, zebrafish Gcsf is required for the specification and proliferation of hematopoietic stem cells, suggesting that Gcsf represents an ancestral cytokine responsible for the broad support of HSPCs. These findings may inform how hematopoietic cytokines evolved following the diversification of teleosts and mammals from a common ancestor. (Blood. 2013;122(24):3918-3928) C1 [Stachura, David L.; Campbell, Clyde A.; Espin-Palazon, Raquel; Lau, Ryan P.; Traver, David] Univ Calif San Diego, Dept Cellular & Mol Med, Sch Med, La Jolla, CA 92093 USA. [Svoboda, Ondrej; Bartunek, Petr] Acad Sci Czech Republic, Inst Mol Genet, Vvi, Prague, Czech Republic. [Zon, Leonard I.; Bartunek, Petr] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Zon, Leonard I.; Bartunek, Petr] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Zon, Leonard I.; Bartunek, Petr] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst,Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Traver, D (reprint author), Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. EM dtraver@ucsd.edu RI Bartunek, Petr/J-3897-2014 OI Bartunek, Petr/0000-0002-6202-7650 FU National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases [K01-DK087814-01A1, R01-DK074482]; Fullbright Scholars award [305/10/0953]; California Institute of Regenerative Medicine New Faculty Award [1-00575-1]; American Heart Association Innovative Science Award [12PILT12860010] FX This work was supported by grants from the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (K01-DK087814-01A1) (D.L.S.), 305/10/0953 projects and Fullbright Scholars award (P.B.), California Institute of Regenerative Medicine New Faculty Award (1-00575-1), American Heart Association Innovative Science Award (#12PILT12860010), and National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK074482) (D.T.). NR 48 TC 22 Z9 23 U1 1 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD DEC 5 PY 2013 VL 122 IS 24 BP 3918 EP 3928 DI 10.1182/blood-2012-12-475392 PG 11 WC Hematology SC Hematology GA 290EV UT WOS:000329737600016 PM 24128862 ER PT J AU Ramanadhan, S Mendez, SR Rao, M Viswanath, K AF Ramanadhan, Shoba Mendez, Samuel R. Rao, Megan Viswanath, Kasisomayajula TI Social media use by community-based organizations conducting health promotion: a content analysis SO BMC PUBLIC HEALTH LA English DT Article DE Community-based organizations; Social media; Health promotion; Content analysis ID NONPROFIT ORGANIZATIONS; PUBLIC-HEALTH; CANCER CONTROL; NETWORKING; INEQUALITIES; ADOPTION; FACEBOOK; OUTCOMES AB Background: Community-based organizations (CBOs) are critical channels for the delivery of health promotion programs. Much of their influence comes from the relationships they have with community members and other key stakeholders and they may be able to harness the power of social media tools to develop and maintain these relationships. There are limited data describing if and how CBOs are using social media. This study assesses the extent to which CBOs engaged in health promotion use popular social media channels, the types of content typically shared, and the extent to which the interactive aspects of social media tools are utilized. Methods: We assessed the social media presence and patterns of usage of CBOs engaged in health promotion in Boston, Lawrence, and Worcester, Massachusetts. We coded content on three popular channels: Facebook, Twitter, and YouTube. We used content analysis techniques to quantitatively summarize posts, tweets, and videos on these channels, respectively. For each organization, we coded all content put forth by the CBO on the three channels in a 30-day window. Two coders were trained and conducted the coding. Data were collected between November 2011 and January 2012. Results: A total of 166 organizations were included in our census. We found that 42% of organizations used at least one of the channels of interest. Across the three channels, organization promotion was the most common theme for content (66% of posts, 63% of tweets, and 93% of videos included this content). Most organizations updated Facebook and Twitter content at rates close to recommended frequencies. We found limited interaction/engagement with audience members. Conclusions: Much of the use of social media tools appeared to be uni-directional, a flow of information from the organization to the audience. By better leveraging opportunities for interaction and user engagement, these organizations can reap greater benefits from the non-trivial investment required to use social media well. Future research should assess links between use patterns and organizational characteristics, staff perspectives, and audience engagement. C1 [Ramanadhan, Shoba; Mendez, Samuel R.; Viswanath, Kasisomayajula] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02215 USA. [Rao, Megan] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. RP Ramanadhan, S (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 450 Brookline Ave,LW 703, Boston, MA 02215 USA. EM Shoba_ramanadhan@dfci.harvard.edu FU National Cancer Institute [5 R01 CA132651] FX This work was funded by the National Cancer Institute (5 R01 CA132651, PI: Viswanath). The authors would also like to acknowledge the PLANET MassCONECT C-PAC, which includes the following members: Community Partners: Clara Savage, EdD (Common Pathways); Ediss Gandelman, MBA, MEd (Beth Israel Deaconness Medical Center); Erline Achille (Boston Public Health Commission); Nashira Baril, MPH (Boston Public Health Commission); and Vilma Lora (YWCA of Greater Lawrence/City of Lawrence Mayor's Health Task Force). Investigators: K. 'Vish' Viswanath, PhD (Harvard School of Public Health/Dana-Farber Cancer Institute); Karen Emmons, PhD, (Harvard School of Public Health/Dana-Farber Cancer Institute); Elaine Puleo, PhD (University of Massachusetts) and Glorian Sorensen, PhD, MPH (Harvard School of Public Health/Dana-Farber Cancer Institute). PLANET MassCONECT Study Team: Jaclyn Alexander-Molloy, MS, Cassandra Andersen, Carmenza Bruff, Josephine Crisostomo, MPH, Lisa Lowery, Sara Minsky, MPH, Shoba Ramanadhan, ScD, MPH (Dana-Farber Cancer Institute). Finally, we would like to thank Rebekah Nagler, PhD, for her guidance on codebook creation and assessing inter-coder reliability. NR 46 TC 10 Z9 10 U1 4 U2 53 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD DEC 5 PY 2013 VL 13 AR 1129 DI 10.1186/1471-2458-13-1129 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 284HA UT WOS:000329305500002 PM 24313999 ER PT J AU Morgan, BA AF Morgan, Bruce A. TI The "Skinny" on Wnt Signaling in Stem Cells SO CELL STEM CELL LA English DT Editorial Material ID EPIDERMIS; FOLLICLE C1 [Morgan, Bruce A.] Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. [Morgan, Bruce A.] Mass Gen Hosp, Boston, MA 02129 USA. RP Morgan, BA (reprint author), Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. EM bmorgan@mgh.harvard.edu NR 10 TC 2 Z9 2 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD DEC 5 PY 2013 VL 13 IS 6 BP 638 EP 640 DI 10.1016/j.stem.2013.11.012 PG 4 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 287VZ UT WOS:000329571700003 PM 24315435 ER PT J AU Wang, L Miao, YL Zheng, XF Lackford, B Zhou, BY Han, L Yao, CG Ward, JM Burkholder, A Lipchina, I Fargo, DC Hochedlinger, K Shi, YS Williams, CJ Hu, G AF Wang, Li Miao, Yi-Liang Zheng, Xiaofeng Lackford, Brad Zhou, Bingying Han, Leng Yao, Chengguo Ward, James M. Burkholder, Adam Lipchina, Inna Fargo, David C. Hochedlinger, Konrad Shi, Yongsheng Williams, Carmen J. Hu, Guang TI The THO Complex Regulates Pluripotency Gene mRNA Export and Controls Embryonic Stem Cell Self-Renewal and Somatic Cell Reprogramming SO CELL STEM CELL LA English DT Article ID GENOME-WIDE ANALYSIS; HUMAN TREX COMPLEX; TRANSCRIPTIONAL NETWORK; MRNP BIOGENESIS; MOUSE; DIFFERENTIATION; EXPRESSION; CIRCUITRY; PROTEIN; NANOG AB Embryonic stem cell (ESC) self-renewal and differentiation are governed by a broad-ranging regulatory network. Although the transcriptional regulatory mechanisms involved have been investigated extensively, posttranscriptional regulation is still poorly understood. Here we describe a critical role of the THO complex in ESC self-renewal and differentiation. We show that THO preferentially interacts with pluripotency gene transcripts through Thoc5 and is required for self-renewal at least in part by regulating their export and expression. During differentiation, THO loses its interaction with those transcripts due to reduced Thoc5 expression, leading to decreased expression of pluripotency proteins that facilitates exit from self-renewal. THO is also important for the establishment of pluripotency, because its depletion inhibits somatic cell reprogramming and blastocyst development. Together, our data indicate that THO regulates pluripotency gene mRNA export to control ESC self-renewal and differentiation, and therefore uncover a role for this aspect of posttranscriptional regulation in stem cell fate specification. C1 [Wang, Li; Zheng, Xiaofeng; Lackford, Brad; Hu, Guang] NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. [Miao, Yi-Liang; Williams, Carmen J.] NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. [Zhou, Bingying] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. [Zhou, Bingying] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Han, Leng] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA. [Yao, Chengguo; Shi, Yongsheng] Univ Calif Irvine, Dept Microbiol & Mol Genet, Sch Med, Irvine, CA 92697 USA. [Ward, James M.; Burkholder, Adam; Fargo, David C.] NIEHS, Res Triangle Pk, NC 27709 USA. [Lipchina, Inna; Hochedlinger, Konrad] Massachusetts Gen Hosp, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, Boston, MA 02114 USA. RP Hu, G (reprint author), NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. EM hug4@niehs.nih.gov RI Williams, Carmen/E-2170-2013; Hu, Guang/E-7474-2016 OI Williams, Carmen/0000-0001-6440-7086; Hu, Guang/0000-0003-0437-4723 FU NIH, National Institute of Environmental Health Sciences [1ZIAES102745, 1ZIAES102985]; NIH [R01GM090056, R01HD058013]; American Cancer Society [RSG-12-186] FX We thank Drs. Karen Adelman, Perry Blackshear, Traci Hall, Raja Jothi, and Paul Wade for critically reading the manuscript. This study was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences 1ZIAES102745 (to L. W., X.Z., B. L., and G. H.) and 1ZIAES102985 (to Y.M. and C. W.), NIH R01GM090056 and American Cancer Society Grant RSG-12-186 (to C.Y. and Y.S.), and NIH R01HD058013 (to I. L. and K.H.). NR 68 TC 23 Z9 24 U1 2 U2 16 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD DEC 5 PY 2013 VL 13 IS 6 BP 676 EP 690 DI 10.1016/j.stem.2013.10.008 PG 15 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 287VZ UT WOS:000329571700011 PM 24315442 ER PT J AU Miller, JD Ganat, YM Kishinevsky, S Bowman, RL Liu, B Tu, EY Mandal, PK Vera, E Shim, JW Kriks, S Taldone, T Fusaki, N Tomishima, MJ Krainc, D Milner, TA Rossi, DJ Studer, L AF Miller, Justine D. Ganat, Yosif M. Kishinevsky, Sarah Bowman, Robert L. Liu, Becky Tu, Edmund Y. Mandal, Pankaj K. Vera, Elsa Shim, Jae-won Kriks, Sonja Taldone, Tony Fusaki, Noemi Tomishima, Mark J. Krainc, Dimitri Milner, Teresa A. Rossi, Derrick J. Studer, Lorenz TI Human iPSC-Based Modeling of Late-Onset Disease via Progerin-Induced Aging SO CELL STEM CELL LA English DT Article ID PLURIPOTENT STEM-CELLS; MODIFIED MESSENGER-RNA; LAMIN-A/C EXPRESSION; PARKINSONS-DISEASE; NEURONAL LOSS; RAT-BRAIN; MOUSE; DIFFERENTIATION; DEGENERATION; GENOME AB Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) resets their identity back to an embryonic age and, thus, presents a significant hurdle for modeling late-onset disorders. In this study, we describe a strategy for inducing aging-related features in human iPSC-derived lineages and apply it to the modeling of Parkinson's disease (PD). Our approach involves expression of progerin, a truncated form of lamin A associated with premature aging. We found that expression of progerin in iPSC-derived fibroblasts and neurons induces multiple aging-related markers and characteristics, including dopamine-specific phenotypes such as neuromelanin accumulation. Induced aging in PD iPSC-derived dopamine neurons revealed disease phenotypes that require both aging and genetic susceptibility, such as pronounced dendrite degeneration, progressive loss of tyrosine hydroxylase (TH) expression, and enlarged mitochondria or Lewy-body-precursor inclusions. Thus, our study suggests that progerin-induced aging can be used to reveal late-onset age-related disease features in hiPSC-based disease models. C1 [Miller, Justine D.; Ganat, Yosif M.; Kishinevsky, Sarah; Liu, Becky; Tu, Edmund Y.; Vera, Elsa; Shim, Jae-won; Kriks, Sonja; Tomishima, Mark J.; Studer, Lorenz] Sloan Kettering Inst Canc Res, Ctr Stem Cell Biol, New York, NY 10065 USA. [Miller, Justine D.; Ganat, Yosif M.; Kishinevsky, Sarah; Liu, Becky; Tu, Edmund Y.; Vera, Elsa; Shim, Jae-won; Kriks, Sonja; Tomishima, Mark J.; Studer, Lorenz] Sloan Kettering Inst Canc Res, Dev Biol Program, New York, NY 10065 USA. [Miller, Justine D.; Bowman, Robert L.] Sloan Kettering Inst Canc Res, Gerstner Sloan Kettering Grad Sch, New York, NY 10065 USA. [Bowman, Robert L.] Sloan Kettering Inst Canc Res, Canc Biol & Genet Program, New York, NY 10065 USA. [Taldone, Tony] Sloan Kettering Inst Canc Res, New York, NY 10065 USA. [Mandal, Pankaj K.; Rossi, Derrick J.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Mandal, Pankaj K.; Rossi, Derrick J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Fusaki, Noemi] DNAVEC Corp, Tsukuba, Ibaraki 3002611, Japan. [Fusaki, Noemi] Keio Univ, Sch Med, Dept Ophthalmol, Shinjuku Ku, Tokyo 1608582, Japan. [Krainc, Dimitri] Harvard Univ, Massachusetts Gen Inst Neurodegenerat Dis, Sch Med, Dept Neurol,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Milner, Teresa A.] Weill Cornell Med Coll, Brain & Mind Res Inst, New York, NY 10065 USA. [Milner, Teresa A.] Rockefeller Univ, Harold & Margaret Milliken Hatch Lab Neuroendocri, New York, NY 10065 USA. RP Studer, L (reprint author), Sloan Kettering Inst Canc Res, Ctr Stem Cell Biol, 1275 York Ave, New York, NY 10065 USA. EM studerl@mskcc.org RI mandal, pankaj/B-4885-2016 FU Phil and Marcia Rothblum foundation by NINDS [NS078338]; Tri-Institutional Stem Cell Initiative (Starr Foundation); NIH [DA08259, HL098351, NS076054]; NSF FX We thank the K. Eggan lab for retroviral-derived control iPSCs, Philip Manos for modified-RNA technical advice, C. Klein for PD fibroblasts, Yvonne Mica and Elizabeth Calder for general technical advice and data interpretation, Andreina Gonzalez, Tracey Van Kempen, and Vladimir Mudragel for help in preparing electron microscopy samples, the MSKCC genomics core laboratory for RNA-seq, MSKCC Molecular Cytology Core facility for histology slices, and MSKCC Cytogenetics core facility for karyotyping. D.J.R. is a New York Stem Cell Foundation Robertson Investigator. The work was supported in part by Phil and Marcia Rothblum foundation by NINDS contract NS078338 and by a grant from the Tri-Institutional Stem Cell Initiative (Starr Foundation) to L. S., and NIH grants DA08259 and HL098351 to T. A. M. and NS076054 to D. K. J.D.M was supported by an NSF fellowship. NR 56 TC 135 Z9 138 U1 4 U2 34 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD DEC 5 PY 2013 VL 13 IS 6 BP 691 EP 705 DI 10.1016/j.stem.2013.11.006 PG 15 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 287VZ UT WOS:000329571700012 PM 24315443 ER PT J AU Bera, A Zhao, SJ Cao, L Chiao, PJ Freeman, JW AF Bera, Alakesh Zhao, Shujie Cao, Lin Chiao, Paul J. Freeman, James W. TI Oncogenic K-Ras and Loss of Smad4 Mediate Invasion by Activating an EGFR/NF-kappa B Axis That Induces Expression of MMP9 and uPA in Human Pancreas Progenitor Cells SO PLOS ONE LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; UROKINASE PLASMINOGEN-ACTIVATOR; FACTOR RECEPTOR; BREAST-CANCER; MATRIX METALLOPROTEINASES; NUCLEAR TRANSLOCATION; TRANSCRIPTION FACTOR; SIGNALING PATHWAY; PROSTATE-CANCER; OVARIAN-CANCER AB Activating K-Ras mutations and inactivating mutations of Smad4 are two common genetic alterations that occur in the development and progression of pancreatic ductal adenocarcinomas (PDAC). To further study the individual and combinatorial roles of these two mutations in the pathogenesis of PDAC, immortalized human pancreas nestin postive cells (HPNE) were genetically modified by either expressing oncogenic K-Ras (HPNE/K-Ras), by shRNA knock down of Smad4 (HPNE/ShSmad4) or by creating both alterations in the same cell line (HPNE/K-Ras/ShSmad4). We previously found that expression of oncogenic K-Ras caused an increase in expression of EGFR and loss of Smad4 further enhanced the up regulation in expression of EGFR and that this increase in EGFR was sufficient to induce invasion. Here we further investigated the mechanism that links mutational alterations and EGFR expression with invasion. The increase in EGFR signaling was associated with up regulation of MMP9 and uPA protein and activity. Moreover, the increase in EGFR signaling promoted a nuclear translocation and binding of RelA (p65), a subunit of NF-kappa B, to the promoters of both MMP-9 and uPA. Treatment of HPNE/K-Ras/ShSmad4 cells with an inhibitor of EGFR reduced EGF-mediated NF-kappa B nuclear translocation and inhibitors of either EGFR or NF-kappa B reduced the increase in MMP-9 or uPA expression. In conclusion, this study provides the mechanism of how a combination of oncogenic K-Ras and loss of Smad4 causes invasion and provides the basis for new strategies to inhibit metastases. C1 [Bera, Alakesh; Zhao, Shujie; Cao, Lin; Freeman, James W.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Med Oncol, San Antonio, TX 78229 USA. [Freeman, James W.] Canc Therapy & Res Ctr S Texas, Expt & Dev Therapeut Program, San Antonio, TX 78229 USA. [Freeman, James W.] Audie L Murphy Mem Vet Adm Med Ctr, Res & Dev, San Antonio, TX USA. [Chiao, Paul J.] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA. RP Freeman, JW (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Med Oncol, San Antonio, TX 78229 USA. EM freemanjw@uthscsa.edu FU VA merit award; Cancer Center; CPRIT; [NIH-RO1CA069122]; [NIH-P30CA054174] FX This work was supported by Grants to JWF, VA merit award, and NIH-RO1CA069122, and Cancer Center Grant to CTRC, NIH-P30CA054174 provided support for the use of Flow Cytometry Core Facility, UTHSCSA and the Optical Imaging Core, UTHSCSA. The work was also supported by CPRIT postdoctoral fellowship to Dr. AB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 63 TC 13 Z9 14 U1 0 U2 11 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 5 PY 2013 VL 8 IS 12 AR e82282 DI 10.1371/journal.pone.0082282 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 273WD UT WOS:000328566100095 PM 24340014 ER PT J AU Duna, J Leahy, RM Li, QZ AF Duna, Joyita Leahy, Richard M. Li, Quanzheng TI Non-Local Means Denoising of Dynamic PET Images SO PLOS ONE LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; BRAIN TRANSFER CONSTANTS; TIME UPTAKE DATA; GRAPHICAL EVALUATION; PARAMETRIC IMAGES; LESION DETECTION; NOISE PROPERTIES; KINETIC-ANALYSIS; RECONSTRUCTION; MODEL AB Objective: Dynamic positron emission tomography (PET), which reveals information about both the spatial distribution and temporal kinetics of a radiotracer, enables quantitative interpretation of PET data. Model-based interpretation of dynamic PET images by means of parametric fitting, however, is often a challenging task due to high levels of noise, thus necessitating a denoising step. The objective of this paper is to develop and characterize a denoising framework for dynamic PET based on non-local means (NLM). Theory: NLM denoising computes weighted averages of voxel intensities assigning larger weights to voxels that are similar to a given voxel in terms of their local neighborhoods or patches. We introduce three key modifications to tailor the original NLM framework to dynamic PET. Firstly, we derive similarities from less noisy later time points in a typical PET acquisition to denoise the entire time series. Secondly, we use spatiotemporal patches for robust similarity computation. Finally, we use a spatially varying smoothing parameter based on a local variance approximation over each spatiotemporal patch. Methods: To assess the performance of our denoising technique, we performed a realistic simulation on a dynamic digital phantom based on the Digimouse atlas. For experimental validation, we denoised [F-18]FDG PET images from a mouse study and a hepatocellular carcinoma patient study. We compared the performance of NLM denoising with four other denoising approaches - Gaussian filtering, PCA, HYPR, and conventional NLM based on spatial patches. Results: The simulation study revealed significant improvement in bias-variance performance achieved using our NLM technique relative to all the other methods. The experimental data analysis revealed that our technique leads to clear improvement in contrast-to-noise ratio in Patlak parametric images generated from denoised preclinical and clinical dynamic images, indicating its ability to preserve image contrast and high intensity details while lowering the background noise variance. C1 [Duna, Joyita; Li, Quanzheng] Massachusetts Gen Hosp, Dept Radiol, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. [Leahy, Richard M.] Univ So Calif, Dept Elect Engn Syst, Inst Signal & Image Proc, Los Angeles, CA 90089 USA. RP Li, QZ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. EM Li.Quanzheng@mgh.harvard.edu FU National Institutes of Health [R21CA149587, R01EB013293, R21EB012326, R01CA165221] FX This work was funded in part by National Institutes of Health R21CA149587, R01EB013293, R21EB012326, and R01CA165221. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 69 TC 0 Z9 0 U1 3 U2 18 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 5 PY 2013 VL 8 IS 12 AR e81390 DI 10.1371/journal.pone.0081390 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 273WD UT WOS:000328566100051 ER PT J AU Mealer, M Kittelson, J Thompson, BT Wheeler, AP Magee, JC Sokol, RJ Moss, M Kahn, MG AF Mealer, Meredith Kittelson, John Thompson, B. Taylor Wheeler, Arthur P. Magee, John C. Sokol, Ronald J. Moss, Marc Kahn, Michael G. TI Remote Source Document Verification in Two National Clinical Trials Networks: A Pilot Study SO PLOS ONE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; ELECTRONIC DATA CAPTURE; DATA QUALITY; VALIDITY; BARRIERS AB Objective: Barriers to executing large-scale randomized controlled trials include costs, complexity, and regulatory requirements. We hypothesized that source document verification (SDV) via remote electronic monitoring is feasible. Methods: Five hospitals from two NIH sponsored networks provided remote electronic access to study monitors. We evaluated pre-visit remote SDV compared to traditional on-site SDV using a randomized convenience sample of all study subjects due for a monitoring visit. The number of data values verified and the time to perform remote and on-site SDV was collected. Results: Thirty-two study subjects were randomized to either remote SDV (N=16) or traditional on-site SDV (N=16). Technical capabilities, remote access policies and regulatory requirements varied widely across sites. In the adult network, only 14 of 2965 data values (0.47%) could not be located remotely. In the traditional on-site SDV arm, 3 of 2608 data values (0.12%) required coordinator help. In the pediatric network, all 198 data values in the remote SDV arm and all 183 data values in the on-site SDV arm were located. Although not statistically significant there was a consistent trend for more time consumed per data value (minutes +/- SD): Adult 0.50 +/- 0.17 min vs. 0.39 +/- 0.10 min (two-tailed t-test p=0.11); Pediatric 0.99 +/- 1.07 min vs. 0.56 +/- 0.61 min (p=0.37) and time per case report form: Adult: 4.60 +/- 1.42 min vs. 3.60 +/- 0.96 min (p=0.10); Pediatric: 11.64 +/- 7.54 min vs. 6.07 +/- 3.18 min (p=0.10) using remote SDV. Conclusions: Because each site had different policies, requirements, and technologies, a common approach to assimilating monitors into the access management system could not be implemented. Despite substantial technology differences, more than 99% of data values were successfully monitored remotely. This pilot study demonstrates the feasibility of remote monitoring and the need to develop consistent access policies for remote study monitoring. C1 [Mealer, Meredith; Moss, Marc] Univ Colorado, Sch Med, Div Pulm Sci & Crit Care Med, Dept Med, Aurora, CO 80045 USA. [Kittelson, John] Colorado Sch Publ Hlth, Dept Biostat & Informat, Aurora, CO USA. [Kittelson, John; Sokol, Ronald J.; Moss, Marc; Kahn, Michael G.] Univ Colorado, Anschutz Med Ctr, Colorado Clin & Translat Sci Inst, Aurora, CO USA. [Thompson, B. Taylor] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Wheeler, Arthur P.] Vanderbilt Univ, Med Ctr, Sch Med, Nashville, TN 37232 USA. [Magee, John C.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Sokol, Ronald J.; Kahn, Michael G.] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO USA. RP Mealer, M (reprint author), Univ Colorado, Sch Med, Div Pulm Sci & Crit Care Med, Dept Med, Aurora, CO 80045 USA. EM Meredith.Mealer@ucdenver.edu FU NIH/NCATS Colorado CTSI Grant [UL1 TR000154]; University of Colorado [HHSN268200536-179C, N01-56167, 2U01DK06243-08]; University of Michigan [CCC: 5U01DK062456-11] FX This work was supported by NIH/NCATS Colorado CTSI Grant Number UL1 TR000154. The ARDS network was supported by HHSN268200536-179C (MGH) and N01-56167 (University of Colorado). The ChilDREN network is supported by CCC: 5U01DK062456-11 (University of Michigan) and 2U01DK06243-08 (University of Colorado). Contents are the authors' sole responsibility and do not necessarily represent official NIH views. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 17 TC 2 Z9 2 U1 2 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 5 PY 2013 VL 8 IS 12 AR e81890 DI 10.1371/journal.pone.0081890 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 273WD UT WOS:000328566100074 PM 24349149 ER PT J AU Scaiewicz, V Nahmias, A Chung, RT Mueller, T Tirosh, B Shibolet, O AF Scaiewicz, Viviana Nahmias, Avital Chung, Raymond T. Mueller, Tobias Tirosh, Boaz Shibolet, Oren TI CCAAT/Enhancer-Binding Protein Homologous (CHOP) Protein Promotes Carcinogenesis in the DEN-Induced Hepatocellular Carcinoma Model SO PLOS ONE LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; INDUCED APOPTOSIS; N-NITROSODIETHYLAMINE; GENE-EXPRESSION; LIVER; HEPATOCARCINOGENESIS; CANCER; CELLS; ATF6; MICE AB Background and Aims: C/EBP homologous protein (CHOP) plays pro-apoptotic roles in the integrated stress response. Recently, a tumor suppressive role for CHOP was demonstrated in lung cancer via regulation of tumor metabolism. To explore the role of CHOP in hepatocarcinogenesis, we induced hepatocellular carcinoma (HCC) in wild type (wt) and CHOP knockout (KO) mice using the carcinogen N-diethylnitrosamine (DEN). Results: Analysis of tumor development showed reduced tumor load, with markedly smaller tumor nodules in the CHOP KO animals, suggesting oncogenic roles of CHOP in carcinogen-induced HCC. In wt tumors, CHOP was exclusively expressed in tumor tissue, with minimal expression in normal parenchyma. Analysis of human adenocarcinomas of various origins demonstrated scattered expression of CHOP in the tumors, pointing to relevance in human pathology. Characterization of pathways that may contribute to preferential expression of CHOP in the tumor identified ATF6 as a potential candidate. ATF6, a key member of the endoplasmic reticulum stress signaling machinery, exhibited a similar pattern of expression as CHOP and strong activation in wt but not CHOP KO tumors. Because HCC is induced by chronic inflammation, we assessed whether CHOP deficiency affects tumor-immune system crosstalk. We found that the number of macrophages and levels of IFN gamma and CCL4 mRNA were markedly reduced in tumors from CHOP KO relative to wt mice, suggesting a role for CHOP in modulating tumor microenvironment and macrophage recruitment to the tumor. Conclusion: Our data highlights a role for CHOP as a positive regulator of carcinogen-induced HCC progression through a complex mechanism that involves the immune system and modulation of stress signaling pathways. C1 [Scaiewicz, Viviana; Tirosh, Boaz] Hebrew Univ Jerusalem, Sch Med, Fac Med, Inst Drug Res, IL-91010 Jerusalem, Israel. [Nahmias, Avital] Hadassah Hebrew Univ Med Ctr, Liver Unit, Div Med, Jerusalem, Israel. [Chung, Raymond T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chung, Raymond T.] Harvard Univ, Sch Med, Boston, MA USA. [Mueller, Tobias] Univ Hosp Leipzig, Sect Hepatol, Dept Gastroenterol & Rheumatol, Leipzig, Germany. [Shibolet, Oren] Tel Aviv Med Ctr & Sch Med, Dept Gastroenterol, Liver Unit, Tel Aviv, Israel. [Shibolet, Oren] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. RP Tirosh, B (reprint author), Hebrew Univ Jerusalem, Sch Med, Fac Med, Inst Drug Res, IL-91010 Jerusalem, Israel. EM boazt@ekmd.huji.ac.il; orensh@tasmc.health.gov.il FU Israel Science Foundation [1668/08, 78/09]; BSF [2007083]; Israel Cancer Association [20110061] FX This research was supported by the Morasha Program of Israel Science Foundation (grant No. 1668/08) to O.S, by the BSF (grant No. 2007083) to O.S and the Israel Cancer Association (20110061) to O.S, and by the Israel Science Foundation (grant 78/09) to BT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 9 Z9 10 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 5 PY 2013 VL 8 IS 12 AR e81065 DI 10.1371/journal.pone.0081065 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 273WD UT WOS:000328566100032 PM 24339898 ER PT J AU Williams, WW Pollak, MR AF Williams, Winfred W. Pollak, Martin R. TI Health Disparities in Kidney Disease - Emerging Data from the Human Genome SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID STAGE RENAL-DISEASE; AFRICAN-AMERICANS; APOL1; RISK; MYH9; GENE AB Racial disparity in end-stage renal disease in the United States is well documented; hypertensive kidney disease has long been considered to be a leading cause of this disorder among black patients. The overall incidence of end-stage renal disease is 3.5 to 5 times as high among black patients as among white patients.(1) Overall, nondiabetic chronic kidney disease afflicts black patients disproportionately. In one study, the rate of nephropathy associated with human immunodeficiency virus infection among black patients was 50 times that among white patients.(2) Research into health disparities has focused on the basis of these differences for more than 20 ... C1 [Williams, Winfred W.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Pollak, Martin R.] Beth Israel Deaconess Med Ctr, Div Nephrol, Boston, MA 02215 USA. [Williams, Winfred W.; Pollak, Martin R.] Harvard Univ, Sch Med, Div Nephrol, Boston, MA USA. [Williams, Winfred W.; Pollak, Martin R.] Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA USA. RP Williams, WW (reprint author), Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. NR 11 TC 6 Z9 6 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 5 PY 2013 VL 369 IS 23 BP 2260 EP 2261 DI 10.1056/NEJMe1312797 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 263II UT WOS:000327801100013 PM 24206461 ER PT J AU Catic, A Suh, CY Hill, CT Daheron, L Henkel, T Orford, KW Dombkowski, DM Liu, T Liu, XS Scadden, DT AF Catic, Andre Suh, Carol Y. Hill, Cedric T. Daheron, Laurence Henkel, Theresa Orford, Keith W. Dombkowski, David M. Liu, Tao Liu, X. Shirley Scadden, David T. TI Genome-wide Map of Nuclear Protein Degradation Shows NCoR1 Turnover as a Key to Mitochondrial Gene Regulation SO CELL LA English DT Article ID TRANSCRIPTIONAL ACTIVATION; LIGASE SIAH2; CREB; PROTEOLYSIS; REPRESSION; HYPOXIA; ADIPOGENESIS; EXPRESSION; RECEPTORS; CHROMATIN AB Transcription factor activity and turnover are functionally linked, but the global patterns by which DNA-bound regulators are eliminated remain poorly understood. We established an assay to define the chromosomal location of DNA-associated proteins that are slated for degradation by the ubiquitin-proteasome system. The genome-wide map described here ties proteolysis in mammalian cells to active enhancers and to promoters of specific gene families. Nuclear-encoded mitochondrial genes in particular correlate with protein elimination, which positively affects their transcription. We show that the nuclear receptor corepressor NCoR1 is a key target of proteolysis and physically interacts with the transcription factor CREB. Proteasome inhibition stabilizes NCoR1 in a site-specific manner and restrains mitochondrial activity by repressing CREB-sensitive genes. In conclusion, this functional map of nuclear proteolysis links chromatin architecture with local protein stability and identifies proteolytic derepression as highly dynamic in regulating the transcription of genes involved in energy metabolism. C1 [Catic, Andre; Suh, Carol Y.; Hill, Cedric T.; Henkel, Theresa; Orford, Keith W.; Dombkowski, David M.; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Catic, Andre; Suh, Carol Y.; Hill, Cedric T.; Daheron, Laurence; Henkel, Theresa; Orford, Keith W.; Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Catic, Andre; Daheron, Laurence; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Henkel, Theresa] Austrian Acad Sci, IMBA, Inst Mol Biotechnol, A-1030 Vienna, Austria. [Dombkowski, David M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Liu, Tao; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Liu, Tao; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Liu, Tao; Liu, X. Shirley] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. RP Catic, A (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. EM catic@post.harvard.edu; david_scadden@harvard.edu RI Liu, Tao/G-3585-2010; OI Liu, Tao/0000-0002-8818-8313; Liu, Tao/0000-0003-0446-9001 FU Margaret Dammann Eisner Foundation; National Institute on Aging [K01-AG036744]; NIH [DK050234] FX We thank Carlota Dao, Laura Prickett-Rice, Kat Folz-Donahue, Meredith Weglarz, Katherine Kulig, Christa Buecker, Hsu-Hsin Chen, Mark Borowsky, Caroline Woo, Youn-Kyoung Lee, Alison Brown, and Vance Morgan for support. T.H. is a fellow of the German National Academic Foundation. A.C. appreciates mentorship by Daniel Finley, Robert Kingston, Derrick Rossi, and Ron Kohanski (NIH/NIA). A.C. is an Irvington Fellow of the Cancer Research Institute and is supported by the Margaret Dammann Eisner Foundation and by National Institute on Aging grant K01-AG036744. D.T.S. is supported by NIH grant DK050234. We thank the reviewers for constructive suggestions and apologize for references we could not include. NR 38 TC 16 Z9 16 U1 1 U2 16 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD DEC 5 PY 2013 VL 155 IS 6 BP 1380 EP 1395 DI 10.1016/j.cell.2013.11.016 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 269VS UT WOS:000328271100020 PM 24315104 ER PT J AU Schwartz, S Agarwala, SD Mumbach, MR Jovanovic, M Mertins, P Shishkin, A Tabach, Y Mikkelsen, TS Satija, R Ruvkun, G Carr, SA Lander, ES Fink, GR Regev, A AF Schwartz, Schraga Agarwala, Sudeep D. Mumbach, Maxwell R. Jovanovic, Marko Mertins, Philipp Shishkin, Alexander Tabach, Yuval Mikkelsen, Tarjei S. Satija, Rahul Ruvkun, Gary Carr, Steven A. Lander, Eric S. Fink, Gerald R. Regev, Aviv TI High-Resolution Mapping Reveals a Conserved, Widespread, Dynamic mRNA Methylation Program in Yeast Meiosis SO CELL LA English DT Article ID SACCHAROMYCES-CEREVISIAE; NUCLEAR-RNA; N-6-METHYLADENOSINE; TRANSCRIPTION; IME4; DIVERGENCE; M(6)A-SEQ; SEQUENCES; RESIDUES; PATHWAY AB N-6-methyladenosine (m(6)A) is the most ubiquitous mRNA base modification, but little is known about its precise location, temporal dynamics, and regulation. Here, we generated genomic maps of m(6)A sites in meiotic yeast transcripts at nearly single-nucleotide resolution, identifying 1,308 putatively methylated sites within 1,183 transcripts. We validated eight out of eight methylation sites in different genes with direct genetic analysis, demonstrated that methylated sites are significantly conserved in a related species, and built a model that predicts methylated sites directly from sequence. Sites vary in their methylation profiles along a dense meiotic time course and are regulated both locally, via predictable methylatability of each site, and globally, through the core meiotic circuitry. The methyltransferase complex components localize to the yeast nucleolus, and this localization is essential for mRNA methylation. Our data illuminate a conserved, dynamically regulated methylation program in yeast meiosis and provide an important resource for studying the function of this epitranscriptomic modification. C1 [Schwartz, Schraga; Mumbach, Maxwell R.; Jovanovic, Marko; Mertins, Philipp; Shishkin, Alexander; Mikkelsen, Tarjei S.; Satija, Rahul; Carr, Steven A.; Lander, Eric S.; Fink, Gerald R.; Regev, Aviv] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Agarwala, Sudeep D.; Fink, Gerald R.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Tabach, Yuval; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Tabach, Yuval; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Lander, Eric S.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Lander, Eric S.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02114 USA. [Regev, Aviv] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA. RP Fink, GR (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. EM gfink@wi.mit.edu; aregev@broadinstitute.org RI Mikkelsen, Tarjei/A-1306-2007; OI Mikkelsen, Tarjei/0000-0002-8133-3135; Schwartz, Schraga/0000-0002-3671-9709 FU National Institutes of Health [GM035010, U54 HG003067]; Broad Institute Funds; NHGRI Pioneer Award; HHMI; HFSP fellowship FX The authors would like to thank Lindsey Dollard and Anna Symbor-Nagrabska for expert technical assistance; Hannah Blitzblau, Mitchell Guttman, and Dmitry Ter-Ovanesyan for fruitful discussions and technical advice; and Leslie Gaffney for making the figures beautiful. The anti-Fob1 antibody was kindly provided by Dr. Stephen Bell. G.R.F. is an American Cancer Society Professor of Genetics. This work was supported by National Institutes of Health Grants GM035010 (G.R.F) and U54 HG003067 (E.S.L.) and Broad Institute Funds. A.R. was supported by an NHGRI Pioneer Award and HHMI. S.S. was supported by an HFSP fellowship. NR 35 TC 114 Z9 122 U1 4 U2 42 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD DEC 5 PY 2013 VL 155 IS 6 BP 1409 EP 1421 DI 10.1016/j.cell.2013.10.047 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 269VS UT WOS:000328271100022 PM 24269006 ER PT J AU Johannessen, CM Johnson, LA Piccioni, F Townes, A Frederick, DT Donahue, MK Narayan, R Flaherty, KT Wargo, JA Root, DE Garraway, LA AF Johannessen, Cory M. Johnson, Laura A. Piccioni, Federica Townes, Aisha Frederick, Dennie T. Donahue, Melanie K. Narayan, Rajiv Flaherty, Keith T. Wargo, Jennifer A. Root, David E. Garraway, Levi A. TI A melanocyte lineage program confers resistance to MAP kinase pathway inhibition SO NATURE LA English DT Article ID MEK INHIBITION; IMPROVED SURVIVAL; BRAF INHIBITION; PROTEIN-KINASE; EXPRESSION; MUTATIONS; MICROPHTHALMIA; TRANSCRIPTION; ONCOGENE; REVEALS AB Malignant melanomas harbouring point mutations (Val600Glu) in the serine/threonine-protein kinase BRAF (BRAF(V600E)) depend on RAF-MEK-ERK signalling for tumour cell growth(1). RAF and MEK inhibitors show remarkable clinical efficacy in BRAF(V600E) melanoma(2,3); however, resistance to these agents remains a formidable challenge(2,4). Global characterization of resistance mechanisms may inform the development of more effective therapeutic combinations. Here we carried out systematic gain-of-function resistance studies by expressing more than 15,500 genes individually in a BRAF(V600E) melanoma cell line treated with RAF, MEK, ERK or combined RAF-MEK inhibitors. These studies revealed a cyclic-AMP-dependent melanocytic signalling network not previously associated with drug resistance, including G-protein-coupled receptors, adenyl cyclase, protein kinase A and cAMP response element binding protein(CREB). Preliminary analysis of biopsies from BRAF (V600E) melanoma patients revealed that phosphorylated (active) CREB was suppressed by RAF-MEK inhibition but restored in relapsing tumours. Expression of transcription factors activated downstream of MAP kinase and cAMP pathways also conferred resistance, including c-FOS, NR4A1, NR4A2 and MITF. Combined treatment with MAPK-pathway and histone-deacetylase inhibitors suppressed MITF expression and cAMP-mediated resistance. Collectively, these data suggest that oncogenic dysregulation of a melanocyte lineage dependency can cause resistance to RAF-MEK-ERK inhibition, which may be overcome by combining signalling-and chromatin-directed therapeutics. C1 [Johannessen, Cory M.; Johnson, Laura A.; Piccioni, Federica; Townes, Aisha; Donahue, Melanie K.; Narayan, Rajiv; Root, David E.; Garraway, Levi A.] Broad Inst Harvard Univ & Massachusetts Inst Tech, Cambridge, MA 02142 USA. [Johannessen, Cory M.; Johnson, Laura A.; Garraway, Levi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Johannessen, Cory M.; Garraway, Levi A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Frederick, Dennie T.; Flaherty, Keith T.; Wargo, Jennifer A.] Massachusetts Gen Hosp, Dept Surg Oncol Med Oncol & Dermatol, Boston, MA 02114 USA. RP Garraway, LA (reprint author), Broad Inst Harvard Univ & Massachusetts Inst Tech, 7 Cambridge Ctr, Cambridge, MA 02142 USA. EM Levi_Garraway@dfci.harvard.edu FU National Institutes of Health (NIH) [DP2 OD002750]; Melanoma Research Alliance; Starr Cancer Consortium; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; NCI Skin Cancer SPORE [P50CA93683]; LINCS Program [U54 HG006093] FX This work was supported by the National Institutes of Health (NIH) Director's New Innovator Award (DP2 OD002750, L. A. G.), Melanoma Research Alliance (L. A. G.), Starr Cancer Consortium (L. A. G.), Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (L. A. G.), the NCI Skin Cancer SPORE (P50CA93683, L. A. G.) and the LINCS Program (U54 HG006093). NR 27 TC 122 Z9 123 U1 2 U2 38 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 5 PY 2013 VL 504 IS 7478 BP 138 EP + DI 10.1038/nature12688 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 264BK UT WOS:000327851700047 PM 24185007 ER PT J AU Neculai, D Schwake, M Ravichandran, M Zunke, F Collins, RF Peters, J Neculai, M Plumb, J Loppnau, P Pizarro, JC Seitova, A Trimble, WS Saftig, P Grinstein, S Dhe-Paganon, S AF Neculai, Dante Schwake, Michael Ravichandran, Mani Zunke, Friederike Collins, Richard F. Peters, Judith Neculai, Mirela Plumb, Jonathan Loppnau, Peter Pizarro, Juan Carlos Seitova, Alma Trimble, William S. Saftig, Paul Grinstein, Sergio Dhe-Paganon, Sirano TI Structure of LIMP-2 provides functional insights with implications for SR-BI and CD36 SO NATURE LA English DT Article ID HIGH-DENSITY-LIPOPROTEIN; RECEPTOR CLASS-B; LIGAND BETA-GLUCOCEREBROSIDASE; SCAVENGER RECEPTOR; BINDING; PHOSPHOLIPIDS; INHIBITORS; PROTEIN; EFFLUX; LIPIDS AB Members of the CD36 superfamily of scavenger receptor proteins are important regulators of lipid metabolism and innate immunity. They recognize normal and modified lipoproteins, as well as pathogen-associated molecular patterns. The family consists of three members: SR-BI (which delivers cholesterol to the liver and steroidogenic organs and is a co-receptor for hepatitis C virus), LIMP-2/LGP85 (which mediates lysosomal delivery of beta-glucocerebrosidase and serves as a receptor for enterovirus 71 and coxsackieviruses) and CD36 (a fatty-acid transporter and receptor for phagocytosis of effete cells and Plasmodium-infected erythrocytes). Notably, CD36 is also a receptor for modified lipoproteins and beta-amyloid, and has been implicated in the pathogenesis of atherosclerosis and of Alzheimer's disease(1). Despite their prominent roles in health and disease, understanding the function and abnormalities of the CD36 family members has been hampered by the paucity of information about their structure. Here we determine the crystal structure of LIMP-2 and infer, by homology modelling, the structure of SR-BI and CD36. LIMP-2 shows a helical bundle where beta-glucocerebrosidase binds, and where ligands are most likely to bind to SR-BI and CD36. Remarkably, the crystal structure also shows the existence of a large cavity that traverses the entire length of the molecule. Mutagenesis of SR-BI indicates that the cavity serves as a tunnel through which cholesterol(esters) are delivered from the bound lipoprotein to the outer leaflet of the plasma membrane. We provide evidence supporting a model(2) whereby lipidic constituents of the ligands attached to the receptor surface are handed off to the membrane through the tunnel, accounting for the selective lipid transfer characteristic of SR-BI and CD36. C1 [Neculai, Dante; Collins, Richard F.; Plumb, Jonathan; Trimble, William S.; Grinstein, Sergio] Hosp Sick Children, Cell Biol Program, Toronto, ON M5G 1X8, Canada. [Schwake, Michael; Zunke, Friederike; Peters, Judith; Saftig, Paul] Univ Kiel, Inst Biochem, D-24118 Kiel, Germany. [Schwake, Michael] Univ Bielefeld, Fak Chem, D-33615 Bielefeld, Germany. [Ravichandran, Mani; Neculai, Mirela; Loppnau, Peter; Pizarro, Juan Carlos; Seitova, Alma; Dhe-Paganon, Sirano] Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L7, Canada. [Pizarro, Juan Carlos] Tulane Univ, Dept Trop Med, New Orleans, LA 70118 USA. [Trimble, William S.; Grinstein, Sergio] Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada. [Grinstein, Sergio] St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, Toronto, ON M5C 1N8, Canada. [Dhe-Paganon, Sirano] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. RP Grinstein, S (reprint author), Hosp Sick Children, Cell Biol Program, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM sergio.grinstein@sickkids.ca RI Saftig, Paul/A-7966-2010; Neculai, Dante/A-9923-2011 FU Canadian Institutes for Health Research [MOP-102474, MOP-126069]; Deutsche Forschungsgemeinschaft [GRK1459, SFB877]; Bohringer Ingelheim Fonds; Canada Research Chair in Molecular Cell Biology; Canadian Institutes for Health Research; Canada Foundation for Innovation; Genome Canada through the Ontario Genomics Institute; GlaxoSmithKline; Karolinska Institutet; Knut and Alice Wallenberg Foundation; Ontario Innovation Trust; Ontario Ministry for Research and Innovation; Merck Co.; Novartis Research Foundation; Swedish Agency for Innovation Systems; Swedish Foundation for Strategic Research; Wellcome Trust FX We thank W. Temple, D. Cossar, S. Graslund, C. Arrowsmith, R. Stahelin, L. Andresen, J. Groth, M. Langer and J. Scott for assistance and discussions. This study was supported by the Canadian Institutes for Health Research (grants MOP-102474 and MOP-126069) and the Deutsche Forschungsgemeinschaft (grants GRK1459 to M. S. and SFB877). F.Z. is supported through the Bohringer Ingelheim Fonds. W. S. T. is the recipient of a Canada Research Chair in Molecular Cell Biology. The Structural Genomics Consortium is a registered charity (number 1097737) that receives funds from the Canadian Institutes for Health Research, the Canada Foundation for Innovation, Genome Canada through the Ontario Genomics Institute, GlaxoSmithKline, Karolinska Institutet, the Knut and Alice Wallenberg Foundation, the Ontario Innovation Trust, the Ontario Ministry for Research and Innovation, Merck & Co., the Novartis Research Foundation, the Swedish Agency for Innovation Systems, the Swedish Foundation for Strategic Research, and the Wellcome Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 21 TC 59 Z9 66 U1 5 U2 38 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 5 PY 2013 VL 504 IS 7478 BP 172 EP 176 DI 10.1038/nature12684 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 264BK UT WOS:000327851700054 PM 24162852 ER PT J AU Ogawa, Y Kim, SK Dana, R Clayton, J Jain, S Rosenblatt, MI Perez, VL Shikari, H Riemens, A Tsubota, K AF Ogawa, Yoko Kim, Stella K. Dana, Reza Clayton, Janine Jain, Sandeep Rosenblatt, Mark I. Perez, Victor L. Shikari, Hasanain Riemens, Anjo Tsubota, Kazuo TI International Chronic Ocular Graft-vs-Host-Disease (GVHD) Consensus Group: Proposed Diagnostic Criteria for Chronic GVHD (Part I) SO SCIENTIFIC REPORTS LA English DT Article ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; DRY EYE DISEASE; MANIFESTATIONS; SEVERITY; SURFACE; COMPLICATIONS; DEFINITION; DIFFERENCE; SCALES AB The International Chronic Ocular GVHD Consensus Group held 4 working meetings to define new diagnostic metrics for chronic ocular graft-versus-host disease (GVHD). After considering the factors currently used to diagnose chronic ocular GVHD, the Consensus Group identified 4 subjective and objective variables to measure in patients following allogeneic hematopoietic stem cell transplantation (HSCT): OSDI, Schirmer's score without anesthesia, corneal staining, and conjunctival injection. Each variable was scored 0-2 or 0-3, with a maximum composite score of 11. Consideration was also given to the presence or the absence of systemic GVHD. On the basis of their composite score and the presence or absence of systemic GVHD, patients were assigned to one of three diagnostic categories: NO, PROBABLE, or DEFINITE ocular GVHD. New diagnostic criteria for chronic ocular GVHD are presented by the Consensus Group. Validation studies are needed to identify the best combination of the proposed metrics to maximize diagnostic sensitivity and specificity. C1 [Ogawa, Yoko; Tsubota, Kazuo] Keio Univ, Sch Med, Dept Ophthalmol, Tokyo, Japan. [Kim, Stella K.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Dana, Reza; Shikari, Hasanain] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Clayton, Janine] NIH, Bethesda, MD 20892 USA. [Jain, Sandeep] Univ Illinois, Corneal Neurobiol Lab, Chicago, IL USA. [Rosenblatt, Mark I.] Weill Cornell Med Coll, New York, NY USA. [Perez, Victor L.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA. [Riemens, Anjo] Univ Med Ctr Utrecht, Utrecht, Netherlands. RP Ogawa, Y (reprint author), Keio Univ, Sch Med, Dept Ophthalmol, Tokyo, Japan. EM yoko@z7.keio.jp FU Global Clinical Research Center Program for Keio University from Japanese Ministry of Health, Labor, and Welfare FX We thank Mizuka Kamoi, Miki Uchino, Yukako Tatematsu, Yumiko Ban, Saori Yaguchi, Isami Hayashi and Catherine Oshima from Department of Ophthalmology, Keio University, Japan; Samantha Herretes from Bascom Palmer Eye Institute, Miami for supporting this collaborative study. This work was supported by the grant for Global Clinical Research Center Program for Keio University from Japanese Ministry of Health, Labor, and Welfare 2011. NR 49 TC 25 Z9 25 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD DEC 5 PY 2013 VL 3 AR 3419 DI 10.1038/srep03419 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 264MB UT WOS:000327880600001 PM 24305504 ER PT J AU Christensen, CP Bedair, H Della Valle, CJ Parvizi, J Schurko, B Jacobs, CA AF Christensen, Christian P. Bedair, Hany Della Valle, Craig J. Parvizi, Javad Schurko, Brian Jacobs, Cale A. TI The Natural Progression of Synovial Fluid White Blood-Cell Counts and the Percentage of Polymorphonuclear Cells After Primary Total Knee Arthroplasty A Multicenter Study SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID INFECTION; DIAGNOSIS AB Background: Assessments of the synovial fluid white blood-cell (WBC) count and percentage of polymorphonuclear cells (PMNs) have been reported to be useful in the diagnosis of periprosthetic joint infection. The purpose of this multicenter retrospective study was to evaluate the natural progression of the synovial fluid WBC count, PMN percentage, and total neutrophil count in patients who underwent knee aspiration during the first two years after primary total knee arthroplasty and had no evidence of periprosthetic joint infection. Methods: From April 1999 to March 2012, 571 patients who presented within the first two years after primary total knee arthroplasty underwent knee aspiration as part of an evaluation for periprosthetic joint infection. Patients were categorized into four groups on the basis of the number of days between surgery and arthrocentesis. The synovial fluid WBC count, PMN percentage, and total neutrophil count were compared among the four time periods with use of separate one-way analyses of variance and Tamhane post-hoc analyses. Results: Four hundred and fifty-two samples not associated with a periprosthetic joint infection were adequate for analysis. The synovial fluid WBC count, PMN percentage, and total neutrophil count all decreased after the first ninety postoperative days. The synovial fluid WBC count showed an earlier return to a level similar to the two-year time point than the PMN percentage did. The mean total neutrophil count decreased from 2533.2 cells/mu L during the first forty-five days to 649.0 cells/mu L from forty-six to ninety days, 269.5 cells/mu L from three months to one year, and 240.8 cells/mu L from one to two years. Conclusions: The synovial fluid WBC count and PMN percentage changed at different rates over the first two years after total knee arthroplasty, with the WBC count exhibiting an initially more rapid decrease and the PMN percentage demonstrating a more linear decrease. Hence, the total neutrophil count, which combines these two parameters, may provide a better method to identify patients with a periprosthetic joint infection. Values for the synovial fluid WBC count, PMN percentage, and total neutrophil count were all significantly elevated in the early postoperative period, and the use of standard cutoff values for the diagnosis of periprosthetic joint infection can lead to false-positive results. C1 [Christensen, Christian P.] Lexington Clin, Lexington, KY 40504 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Rush Univ, Med Ctr, Chicago, IL 60612 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. RP Christensen, CP (reprint author), Lexington Clin, 1221 South Broadway Dr, Lexington, KY 40504 USA. EM calejacobs@hotmail.com NR 7 TC 6 Z9 6 U1 0 U2 5 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 EI 1535-1386 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD DEC 4 PY 2013 VL 95A IS 23 BP 2081 EP 2087 DI 10.2106/JBJS.L.01646 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 266FV UT WOS:000328009700001 PM 24306694 ER PT J AU Sherrill, KR Erdem, UM Ross, RS Brown, TI Hasselmo, ME Stern, CE AF Sherrill, Katherine R. Erdem, Ugur M. Ross, Robert S. Brown, Thackery I. Hasselmo, Michael E. Stern, Chantal E. TI Hippocampus and Retrosplenial Cortex Combine Path Integration Signals for Successful Navigation SO JOURNAL OF NEUROSCIENCE LA English DT Article DE navigation; time; memory; parahippocampal cortex; posterior parietal cortex; optic flow ID HUMAN SPATIAL NAVIGATION; PARIETAL CORTEX; VENTRAL HIPPOCAMPUS; ENTORHINAL CORTEX; HUMAN BRAIN; MODEL; HUMANS; MEMORY; RAT; CELLS AB The current study used fMRI in humans to examine goal-directed navigation in an open field environment. We designed a task that required participants to encode survey-level spatial information and subsequently navigate to a goal location in either first person, third person, or survey perspectives. Critically, no distinguishing landmarks or goal location markers were present in the environment, thereby requiring participants to rely on path integration mechanisms for successful navigation. We focused our analysis on mechanisms related to navigation and mechanisms tracking linear distance to the goal location. Successful navigation required translation of encoded survey-level map information for orientation and implementation of a planned route to the goal. Our results demonstrate that successful first and third person navigation trials recruited the anterior hippocampus more than trials when the goal location was not successfully reached. When examining only successful trials, the retrosplenial and posterior parietal cortices were recruited for goal-directed navigation in both first person and third person perspectives. Unique to first person perspective navigation, the hippocampus was recruited to path integrate self-motion cues with location computations toward the goal location. Last, our results demonstrate that the hippocampus supports goal-directed navigation by actively tracking proximity to the goal throughout navigation. When using path integration mechanisms in first person and third person perspective navigation, the posterior hippocampus was more strongly recruited as participants approach the goal. These findings provide critical insight into the neural mechanisms by which we are able to use map-level representations of our environment to reach our navigational goals. C1 [Sherrill, Katherine R.; Erdem, Ugur M.; Ross, Robert S.; Brown, Thackery I.; Hasselmo, Michael E.; Stern, Chantal E.] Boston Univ, Ctr Memory & Brain, Boston, MA 02215 USA. [Sherrill, Katherine R.; Ross, Robert S.; Brown, Thackery I.; Stern, Chantal E.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Sherrill, KR (reprint author), Boston Univ, Ctr Memory & Brain, 2 Cummington Mall, Boston, MA 02215 USA. EM krmck@bu.edu OI Ross, Robert/0000-0002-3987-881X; Hasselmo, Michael/0000-0002-9925-6377 FU Office of Naval Research (ONR) Multidisciplinary University Research Initiative (MURI) [N00014-10-1-0936]; NCRR [P41RR14075] FX This work was conducted with the support of the Office of Naval Research (ONR) Multidisciplinary University Research Initiative (MURI) (N00014-10-1-0936). fMRI scanning was completed at the Athinoula A. Martinos Center for Biomedical Imaging (Charlestown, MA) which receives support from NCRR P41RR14075. We thank Henry Eve for assistance with analyzing statistical data, and Randall Newmark for assistance with fMRI data collection. NR 48 TC 37 Z9 37 U1 2 U2 14 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 4 PY 2013 VL 33 IS 49 BP 19304 EP 19313 DI 10.1523/JNEUROSCI.1825-13.2013 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 267PO UT WOS:000328110100026 PM 24305826 ER PT J AU Wei, B Dai, MJ Myhrvold, C Ke, YG Jungmann, R Yin, P AF Wei, Bryan Dai, Mingjie Myhrvold, Cameron Ke, Yonggang Jungmann, Ralf Yin, Peng TI Design Space for Complex DNA Structures SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID ATOMIC-FORCE MICROSCOPY; SINGLE-STRANDED-DNA; NANOSCALE SHAPES; FOLDING DNA; ORIGAMI; NANOSTRUCTURES; JUNCTIONS; RNA; NANOTUBES; MOLECULES AB Nucleic acids have emerged as effective materials for assembling complex nanoscale structures. To tailor the structures to function optimally for particular applications, a broad structural design space is desired. Despite the many discrete and extended structures demonstrated in the past few decades, the design space remains to be fully explored. In particular, the complex finite-sized structures produced to date have been typically based on a small number of structural motifs. Here, we perform a comprehensive study of the design space for complex DNA structures, using more than 30 distinct motifs derived from single-stranded tiles. These motifs self-assemble to form structures with diverse strand weaving patterns and specific geometric properties, such as curvature and twist. We performed a systematic study to control and characterize the curvature of the structures, and constructed a flat structure with a corrugated strand pattern. The work here reveals the broadness of the design space for complex DNA nanostructures. C1 [Wei, Bryan; Dai, Mingjie; Myhrvold, Cameron; Ke, Yonggang; Jungmann, Ralf; Yin, Peng] Harvard Univ, Sch Med, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Wei, Bryan; Myhrvold, Cameron; Jungmann, Ralf; Yin, Peng] Harvard Univ, Dept Syst Biol, Boston, MA 02115 USA. [Dai, Mingjie] Harvard Univ, Program Biophys, Boston, MA 02115 USA. [Ke, Yonggang] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Yin, P (reprint author), Harvard Univ, Sch Med, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. EM py@hms.harvard.edu RI Jungmann, Ralf/A-6357-2015; OI Jungmann, Ralf/0000-0003-4607-3312; Dai, Mingjie/0000-0002-8665-4966 FU Office of Naval Research (ONR) Young Investigator Program award [N000141110914]; ONR grant [N000141010827]; National Science Foundation (NSF) Faculty Early Career Development Award [1054898]; NSF grant [1162459]; National Institutes of Health Director's New Innovator Award [IDP2OD007292]; Wyss Institute Faculty Startup Fund; Howard Hughes Medical Institute; Fannie and John Hertz Foundation; Alexander von Humboldt Foundation FX We thank Wei Sun and Hoang Lu for technical assistance and David Zhang, Erik Winfree, William Sherman, and Robert Barish for discussion. DNA-PAINT data were collected at the Nikon Imaging Center at Harvard Medical School. This work was funded by Office of Naval Research (ONR) Young Investigator Program award N000141110914, ONR grant N000141010827, National Science Foundation (NSF) Faculty Early Career Development Award 1054898, NSF grant 1162459, National Institutes of Health Director's New Innovator Award IDP2OD007292, and a Wyss Institute Faculty Startup Fund to P.Y. M.D. acknowledges an international student research fellowship from the Howard Hughes Medical Institute. C.M. acknowledges a graduate research fellowship from the Fannie and John Hertz Foundation. R.J. acknowledges a postdoctoral fellowship from the Alexander von Humboldt Foundation. NR 51 TC 16 Z9 16 U1 7 U2 75 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 4 PY 2013 VL 135 IS 48 BP 18080 EP 18088 DI 10.1021/ja4062294 PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA 267LU UT WOS:000328100000017 PM 24256506 ER PT J AU Lim, S Kim, KM Kim, MJ Woo, SJ Choi, SH Park, KS Jang, HC Meigs, JB Wexler, DJ AF Lim, Soo Kim, Kyoung Min Kim, Min Joo Woo, Se Joon Choi, Sung Hee Park, Kyong Soo Jang, Hak Chul Meigs, James B. Wexler, Deborah J. TI The Association of Maximum Body Weight on the Development of Type 2 Diabetes and Microvascular Complications: MAXWEL Study SO PLOS ONE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; BETA-CELL FUNCTION; LIFE-STYLE; INSULIN ACTION; RISK-FACTORS; US ADULTS; OBESITY; OVERWEIGHT; DISEASE; MELLITUS AB Background: Obesity precedes the development of type 2 diabetes (T2D). However, the relationship between the magnitude and rate of weight gain to T2D development and complications, especially in non-White populations, has received less attention. Methods and Findings: We determined the association of rate and magnitude of weight gain to age at T2D diagnosis (Age(T2D)), HbA1c at T2D diagnosis (HbA1c(T2D)), microalbuminuria, and diabetic retinopathy after adjusting for sex, BMI at age 20 years, lifestyles, family history of T2D and/or blood pressure and lipids in 2164 Korean subjects aged >= 30 years and newly diagnosed with diabetes. Body weight at age 20 years (Wt(20y)) was obtained by recall or from participants' medical, school, or military records. Participants recalled their maximum weight (Wt(max)) prior to T2D diagnosis and age at maximum weight (Age(max_wt)). The rate of weight gain (Rate(max_wt)) was calculated from magnitude of weight gain (Delta Wt = Wt(max)-Wt(20y)) divided by Delta Time (Age(max_wt) -20 years). The mean Age(max_wt) and Age(T2D) were 41.5 +/- 10.9 years and 50.1 +/- 10.5 years, respectively. The Wt(20y) and Wt(max) were 59.9 +/- 10.5 kg and 72.9 +/- 11.4 kg, respectively. The Rate(max_wt) was 0.56 +/- 0.50 kg/year. After adjusting for risk factors, greater Delta Wt and higher Rate(max_wt) were significantly associated with earlier Age(T2D), higher HbA1c(T2D) after additional adjusting for Age(T2D), and microalbuminuria after further adjusting for HbA1c(T2D) and lipid profiles. Greater Delta Wt and higher Rate(max_wt) were also significantly associated with diabetic retinopathy. Conclusions: This finding supports public health recommendations to reduce the risk of T2D and its complications by preventing weight gain from early adulthood. C1 [Lim, Soo; Kim, Kyoung Min; Choi, Sung Hee; Jang, Hak Chul] Seoul Natl Univ, Coll Med, Dept Internal Med, Songnam, South Korea. [Lim, Soo; Kim, Kyoung Min; Woo, Se Joon; Choi, Sung Hee; Jang, Hak Chul] Seoul Natl Univ, Bundang Hosp, Songnam, South Korea. [Woo, Se Joon] Seoul Natl Univ, Coll Med, Dept Ophthalmol, Songnam, South Korea. [Kim, Min Joo] Korea Canc Ctr Hosp, Dept Internal Med, Seoul, South Korea. [Park, Kyong Soo] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea. [Lim, Soo; Meigs, James B.] Harvard Univ, Sch Med, Div Gen Med, Boston, MA USA. [Wexler, Deborah J.] Harvard Univ, Sch Med, Ctr Diabet, Boston, MA USA. [Lim, Soo; Meigs, James B.; Wexler, Deborah J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lim, Soo; Meigs, James B.; Wexler, Deborah J.] Harvard Univ, Sch Med, Boston, MA USA. RP Jang, HC (reprint author), Seoul Natl Univ, Coll Med, Dept Internal Med, Songnam, South Korea. EM janghak@snu.ac.kr RI Park, Kyong Soo/C-2265-2008; OI Park, Kyong Soo/0000-0003-3597-342X; CHOI, SUNG HEE/0000-0003-0740-8116 FU National Research Foundation; Korea government [2006-2005410]; Seoul National University Bundang Hospital; NIDDK [K23 DK 080228-05] FX This study was supported by the National Research Foundation grant funded by the Korea government (2006-2005410). SL receives support from Seoul National University Bundang Hospital. DJW is supported by an NIDDK Career Development Award (K23 DK 080228-05). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 33 TC 4 Z9 4 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 4 PY 2013 VL 8 IS 12 AR e80525 DI 10.1371/journal.pone.0080525 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 265KD UT WOS:000327949300027 PM 24324607 ER PT J AU Nyendak, MR Park, B Null, MD Baseke, J Swarbrick, G Mayanja-Kizza, H Nsereko, M Johnson, DF Gitta, P Okwera, A Goldberg, S Bozeman, L Johnson, JL Boom, WH Lewinsohn, DA Lewinsohn, DM AF Nyendak, Melissa R. Park, Byung Null, Megan D. Baseke, Joy Swarbrick, Gwendolyn Mayanja-Kizza, Harriet Nsereko, Mary Johnson, Denise F. Gitta, Phineas Okwera, Alphonse Goldberg, Stefan Bozeman, Lorna Johnson, John L. Boom, W. Henry Lewinsohn, Deborah A. Lewinsohn, David M. CA TB Res Unit TB Trials Consortium TI Mycobacterium tuberculosis Specific CD8(+) T Cells Rapidly Decline with Antituberculosis Treatment SO PLOS ONE LA English DT Article ID INTERFERON-GAMMA RESPONSES; PULMONARY TUBERCULOSIS; IFN-GAMMA; ANTIGEN; INFECTION; MALNUTRITION; INDIVIDUALS; BIOMARKERS; SIGNATURE; REVERSION AB Rationale: Biomarkers associated with response to therapy in tuberculosis could have broad clinical utility. We postulated that the frequency of Mycobacterium tuberculosis (Mtb) specific CD8(+) T cells, by virtue of detecting intracellular infection, could be a surrogate marker of response to therapy and would decrease during effective antituberculosis treatment. Objectives: We sought to determine the relationship of Mtb specific CD4(+) T cells and CD8(+) T cells with duration of antituberculosis treatment. Materials and Methods: We performed a prospective cohort study, enrolling between June 2008 and August 2010, of HIV-uninfected Ugandan adults (n = 50) with acid-fast bacillus smear-positive, culture confirmed pulmonary TB at the onset of antituberculosis treatment and the Mtb specific CD4(+) and CD8(+) T cell responses to ESAT-6 and CFP-10 were measured by IFN-gamma ELISPOT at enrollment, week 8 and 24. Results: There was a significant difference in the Mtb specific CD8(+) T response, but not the CD4(+) T cell response, over 24 weeks of antituberculosis treatment (p<0.0001), with an early difference observed at 8 weeks of therapy (p = 0.023). At 24 weeks, the estimated Mtb specific CD8(+) T cell response decreased by 58%. In contrast, there was no significant difference in the Mtb specific CD4(+) T cell during the treatment. The Mtb specific CD4(+) T cell response, but not the CD8(+) response, was negatively impacted by the body mass index. Conclusions: Our data provide evidence that the Mtb specific CD8(+) T cell response declines with antituberculosis treatment and could be a surrogate marker of response to therapy. Additional research is needed to determine if the Mtb specific CD8(+) T cell response can detect early treatment failure, relapse, or to predict disease progression. C1 [Nyendak, Melissa R.; Lewinsohn, David M.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Park, Byung] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Null, Megan D.; Lewinsohn, Deborah A.] Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97201 USA. [Baseke, Joy; Mayanja-Kizza, Harriet; Nsereko, Mary; Gitta, Phineas; Okwera, Alphonse; Johnson, John L.; Boom, W. Henry] Uganda Case Western Reserve Univ, Res Collaborat, Kampala, Uganda. [Swarbrick, Gwendolyn; Lewinsohn, David M.] Portland VA Med Ctr, Dept Med, Portland, OR USA. [Mayanja-Kizza, Harriet] Makerere Univ, Coll Hlth Sci, Dept Med, Kampala, Uganda. [Johnson, Denise F.; Johnson, John L.; Boom, W. Henry] Case Western Reserve Univ, TB Res Unit, Cleveland, OH 44106 USA. [Goldberg, Stefan; Bozeman, Lorna] Ctr Dis Control & Prevent, TB Trials Consortium, Natl Ctr HIV AIDS Viral Hepatitis & TB Prevent, Div TB Eliminat, Atlanta, GA USA. RP Nyendak, MR (reprint author), Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. EM nyendakm@ohsu.edu; lewinsod@ohsu.edu RI Lewinsohn, David/I-4936-2013 OI Mayanja-Kizza, Harriet/0000-0002-9297-6208; Lewinsohn, David/0000-0001-9906-9494 FU NIH [HHSN266200400081C, HHSN272200900053C]; National Center for Research Resources [KL2RR024141]; VA Merit Review Grant; Portland VA Medical Center; Tuberculosis Research Unit at Case Western Reserve University; United States National Institute of Allergy and Infectious Diseases, National Institutes of Health and Human Services [HHSN266200700022C/NO1-AI-70022]; US Government Division of Tuberculosis Elimination, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention (CDC) [200-2009-32598] FX This work was supported in part by the following agency and institutes: NIH grants HHSN266200400081C and HHSN272200900053C, The National Center for Research Resources KL2RR024141, VA Merit Review Grant and the Portland VA Medical Center. This work was also supported by the Tuberculosis Research Unit at Case Western Reserve University, established with funds from the United States National Institute of Allergy and Infectious Diseases, National Institutes of Health and Human Services, under contract number HHSN266200700022C/NO1-AI-70022 and the Tuberculosis Trials Consortium sponsored by the US Government Division of Tuberculosis Elimination, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention (CDC), contract number 200-2009-32598. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the CDC or the Agency for Toxic Substances and Disease Registry. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 44 TC 15 Z9 15 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 4 PY 2013 VL 8 IS 12 AR e81564 DI 10.1371/journal.pone.0081564 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 265KD UT WOS:000327949300095 PM 24324704 ER PT J AU Zurcher, NR Rogier, O Boshyan, J Hippolyte, L Russo, B Gillberg, N Helles, A Ruest, T Lemonnier, E Gillberg, C Hadjikhani, N AF Zuercher, Nicole R. Rogier, Ophelie Boshyan, Jasmine Hippolyte, Loyse Russo, Britt Gillberg, Nanna Helles, Adam Ruest, Torsten Lemonnier, Eric Gillberg, Christopher Hadjikhani, Nouchine TI Perception of Social Cues of Danger in Autism Spectrum Disorders SO PLOS ONE LA English DT Article ID PERCEIVED GAZE DIRECTION; HIGH-FUNCTIONING ADULTS; FACIAL EXPRESSION; ASPERGER-SYNDROME; EYE GAZE; NEURAL SYSTEMS; DIAGNOSTIC INTERVIEW; AMYGDALA RESPONSES; BRAIN MECHANISMS; FEARFUL FACES AB Intuitive grasping of the meaning of subtle social cues is particularly affected in autism spectrum disorders (ASD). Despite their relevance in social communication, the effect of averted gaze in fearful faces in conveying a signal of environmental threat has not been investigated using real face stimuli in adults with ASD. Here, using functional MRI, we show that briefly presented fearful faces with averted gaze, previously shown to be a strong communicative signal of environmental danger, produce different patterns of brain activation than fearful faces with direct gaze in a group of 26 normally intelligent adults with ASD compared with 26 matched controls. While implicit cue of threat produces brain activation in attention, emotion processing and mental state attribution networks in controls, this effect is absent in individuals with ASD. Instead, individuals with ASD show activation in the subcortical face-processing system in response to direct eye contact. An effect of differences in looking behavior was excluded in a separate eye tracking experiment. Our data suggest that individuals with ASD are more sensitive to direct eye contact than to social signals of danger conveyed by averted fearful gaze. C1 [Zuercher, Nicole R.; Rogier, Ophelie; Hippolyte, Loyse; Russo, Britt; Ruest, Torsten; Hadjikhani, Nouchine] Ecole Polytech Fed Lausanne, Brain Mind Inst, CH-1015 Lausanne, Switzerland. [Zuercher, Nicole R.; Boshyan, Jasmine; Hadjikhani, Nouchine] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Gillberg, Nanna; Helles, Adam; Gillberg, Christopher; Hadjikhani, Nouchine] Univ Gothenburg, Gillberg Centrum, Gothenburg, Sweden. [Lemonnier, Eric] Univ Brest, Neurosci Lab, Brest, France. RP Hadjikhani, N (reprint author), Ecole Polytech Fed Lausanne, Brain Mind Inst, CH-1015 Lausanne, Switzerland. EM nouchine@nmr.mgh.harvard.edu RI Centre d'imagerie Biomedicale, CIBM/B-5740-2012; OI Hadjikhani, Nouchine/0000-0003-4075-3106 FU Swiss National Science Foundation [PP00P3-130191]; Velux Stiftung; Centre d'Imagerie BioMedicale (CIBM) of the University of Lausanne (UNIL); Swiss Federal Institute of Technology Lausanne (EPFL); University of Geneva (UniGe); Centre Hospitalier Universitaire Vaudois (CHUV); Hopitaux Universitaires de Geneve (HUG); Leenaards Foundation; Jeantet Foundation FX This work was supported by the Swiss National Science Foundation PP00P3-130191 to NH and by the Velux Stiftung, by the Centre d'Imagerie BioMedicale (CIBM) of the University of Lausanne (UNIL), the Swiss Federal Institute of Technology Lausanne (EPFL), the University of Geneva (UniGe), the Centre Hospitalier Universitaire Vaudois (CHUV), the Hopitaux Universitaires de Geneve (HUG), and the Leenaards and the Jeantet Foundations. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 82 TC 2 Z9 2 U1 7 U2 22 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 4 PY 2013 VL 8 IS 12 AR e81206 DI 10.1371/journal.pone.0081206 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 265KD UT WOS:000327949300081 PM 24324679 ER PT J AU Dhaliwal, G Hauer, KE AF Dhaliwal, Gurpreet Hauer, Karen E. TI The Oral Patient Presentation in the Era of Night Float Admissions Credit and Critique SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Dhaliwal, Gurpreet; Hauer, Karen E.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, Med Serv, San Francisco, CA USA. RP Dhaliwal, G (reprint author), San Francisco VA Med Ctr, 4150 Clement St 111, San Francisco, CA 94121 USA. EM gurpreet.dhaliwal@ucsf.edu NR 5 TC 5 Z9 5 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 4 PY 2013 VL 310 IS 21 BP 2247 EP 2248 DI 10.1001/jama.2013.282322 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 262OV UT WOS:000327746300004 PM 24302082 ER PT J AU Curtis, JR Back, AL Ford, DW Downey, L Shannon, SE Doorenbos, AZ Kross, EK Reinke, LF Feemster, LC Edlund, B Arnold, RW O'Connor, K Engelberg, RA AF Curtis, J. Randall Back, Anthony L. Ford, Dee W. Downey, Lois Shannon, Sarah E. Doorenbos, Ardith Z. Kross, Erin K. Reinke, Lynn F. Feemster, Laura C. Edlund, Barbara Arnold, Richard W. O'Connor, Kim Engelberg, Ruth A. TI Effect of Communication Skills Training for Residents and Nurse Practitioners on Quality of Communication With Patients With Serious Illness A Randomized Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID OF-LIFE CARE; EARLY PALLIATIVE CARE; CELL LUNG-CANCER; DYING PATIENTS; PHYSICIAN COMMUNICATION; CHRONIC DISEASE; MENTAL-HEALTH; MEDICAL-CARE; END; PERSPECTIVES AB IMPORTANCE Communication about end-of-life care is a core clinical skill. Simulation-based training improves skill acquisition, but effects on patient-reported outcomes are unknown. OBJECTIVE To assess the effects of a communication skills intervention for internal medicine and nurse practitioner trainees on patient- and family-reported outcomes. DESIGN, SETTING, AND PARTICIPANTS Randomized trial conducted with 391 internal medicine and 81 nurse practitioner trainees between 2007 and 2013 at the University of Washington and Medical University of South Carolina. INTERVENTION Participants were randomized to an 8-session, simulation-based, communication skills intervention (N = 232) or usual education (N = 240). MAIN OUTCOMES AND MEASURES Primary outcome was patient- reported quality of communication (QOC; mean rating of 17 items rated from 0-10, with 0 = poor and 10 = perfect). Secondary outcomes were patient- reported quality of end-of-life care (QEOLC; mean rating of 26 items rated from 0-10) and depressive symptoms (assessed using the 8-item Personal Health Questionnaire [PHQ-8]; range, 0-24, higher scores worse) and family-reported QOC and QEOLC. Analyses were clustered by trainee. RESULTS There were 1866 patient ratings (44% response) and 936 family ratings (68% response). The intervention was not associated with significant changes in QOC or QEOLC. Mean values for postintervention patient QOC and QEOLC were 6.5 (95% CI, 6.2 to 6.8) and 8.3 (95% CI, 8.1 to 8.5) respectively, compared with 6.3 (95% CI, 6.2 to 6.5) and 8.3 (95% CI, 8.1 to 8.4) for control conditions. After adjustment, comparing intervention with control, there was no significant difference in the QOC score for patients (difference, 0.4 points [95% CI, -0.1 to 0.9]; P = .15) or families (difference, 0.1 [95% CI, -0.8 to 1.0]; P = .81). There was no significant difference in QEOLC score for patients (difference, 0.3 points [95% CI, -0.3 to 0.8]; P = .34) or families (difference, 0.1 [95% CI, -0.7 to 0.8]; P = .88). The intervention was associated with significantly increased depression scores among patients of postintervention trainees (mean score, 10.0 [95% CI, 9.1 to 10.8], compared with 8.8 [95% CI, 8.4 to 9.2]) for control conditions; adjusted model showed an intervention effect of 2.2 (95% CI, 0.6 to 3.8; P = .006). CONCLUSIONS AND RELEVANCE Among internal medicine and nurse practitioner trainees, simulation-based communication training compared with usual education did not improve quality of communication about end-of-life care or quality of end-of-life care but was associated with a small increase in patients' depressive symptoms. These findings raise questions about skills transfer from simulation training to actual patient care and the adequacy of communication skills assessment. C1 [Curtis, J. Randall; Downey, Lois; Kross, Erin K.; Feemster, Laura C.; Engelberg, Ruth A.] Univ Washington, Harborview Med Ctr, Div Pulm & Crit Care, Dept Med, Seattle, WA 98104 USA. [Curtis, J. Randall; Shannon, Sarah E.; Doorenbos, Ardith Z.; Reinke, Lynn F.] Univ Washington, Sch Nursing, Dept Biobehav Nursing & Hlth Syst, Seattle, WA 98104 USA. [Back, Anthony L.] Univ Washington, Dept Med, Div Med Oncol, Seattle Canc Care Alliance, Seattle, WA 98104 USA. [Back, Anthony L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Ford, Dee W.] Med Univ S Carolina, Dept Med, Div Pulm & Crit Care, Charleston, SC USA. [Reinke, Lynn F.; Feemster, Laura C.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Edlund, Barbara] Med Univ S Carolina, Coll Nursing, Charleston, SC USA. [Arnold, Richard W.; O'Connor, Kim] Univ Washington, Dept Med, Seattle, WA 98104 USA. RP Curtis, JR (reprint author), Univ Washington, Harborview Med Ctr, Div Pulm & Crit Care, Box 359762, Seattle, WA 98104 USA. EM jrc@u.washington.edu FU National Institute of Nursing Research of the National Institutes of Health [R01NR009987] FX This study was supported by the National Institute of Nursing Research of the National Institutes of Health (R01NR009987). NR 41 TC 88 Z9 88 U1 7 U2 48 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 4 PY 2013 VL 310 IS 21 BP 2271 EP 2281 DI 10.1001/jama.2013.282081 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 262OV UT WOS:000327746300012 PM 24302090 ER PT J AU Smith, MR AF Smith, Matthew R. TI Androgen Deprivation Therapy and Acute Kidney Injury SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID PROSTATE-CANCER; RADIOTHERAPY; GOSERELIN C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Yawkey 7030, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 4 PY 2013 VL 310 IS 21 BP 2313 EP 2313 DI 10.1001/jama.2013.281599 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 262OV UT WOS:000327746300020 PM 24302098 ER PT J AU Nation, DA Edland, SD Bondi, MW Salmon, DP Delano-Wood, L Peskind, ER Quinn, JF Galasko, DR AF Nation, Daniel A. Edland, Steven D. Bondi, Mark W. Salmon, David P. Delano-Wood, Lisa Peskind, Elaine R. Quinn, Joseph F. Galasko, Douglas R. TI Pulse pressure is associated with Alzheimer biomarkers in cognitively normal older adults SO NEUROLOGY LA English DT Article ID BLOOD-PRESSURE; DISEASE; AGE AB Objective: The current study examined the association between pulse pressure (PP) and CSF-based biomarkers for Alzheimer disease, including beta-amyloid 1-42 (A beta(1-42)) and phosphorylated tau (P-tau) protein, in cognitively normal older adults. Methods: One hundred seventy-seven cognitively normal, stroke-free older adult participants (aged 55-100 years) underwent blood pressure assessment for determination of PP (systolic - diastolic blood pressure) and lumbar puncture for measurement of CSF A beta(1-42) and P-tau. Pearson correlations and multiple linear regression, controlling for age, sex, APOE genotype, and body mass index, evaluated the relationship between PP and Alzheimer disease biomarkers. Results: PP elevation was associated with increased P-tau (r = 0.23, p = 0.002), reduced A beta(1-42) (r=-20.19, p = 0.01), and increased P-tau to A beta(1-42) ratio (r = 0.27, p < 0.001). After controlling for covariates, PP remained associated with P-tau (beta = 0.18, p = 0.0196) and P-tau to A beta(1-42) ratio (beta = 0.0016, p < 0.001) but was no longer associated with A beta(1-42) (beta = -0.1, p = 0.35). Post hoc multivariate analyses indicated that increased PP was associated with all biomarkers in younger participants (aged 55-70 years) (A beta(1-42): p = 0.050; P-tau: p = 0.003; P-tau to A beta ratio: p = 0.0007) but not older participants (aged 70-100 years). Conclusions: PP elevation is associated with increased CSF P-tau and decreased Ab1-42 in cognitively normal older adults, suggesting that pulsatile hemodynamics may be related to amyloidosis and tau-related neurodegeneration. The relationship between PP and CSF biomarkers is age-dependent and observed only in participants in the fifth and sixth decades of life. C1 [Nation, Daniel A.; Bondi, Mark W.; Delano-Wood, Lisa] Vet Affairs San Diego Healthcare Syst, San Diego, CA 92161 USA. [Edland, Steven D.; Salmon, David P.; Galasko, Douglas R.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Bondi, Mark W.; Delano-Wood, Lisa] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Peskind, Elaine R.] Mental Illness Res Educ & Clin Ctr, VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Peskind, Elaine R.] Univ Washington, Sch Med, Dept Psychiat, Seattle, WA USA. [Peskind, Elaine R.] Univ Washington, Sch Med, Dept Behav Sci, Seattle, WA USA. [Quinn, Joseph F.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Quinn, Joseph F.] Portland VA Med Ctr, Portland, OR USA. RP Nation, DA (reprint author), Vet Affairs San Diego Healthcare Syst, San Diego, CA 92161 USA. EM dnation@ucsd.edu FU Alzheimer's Association [IIRG 07-59343]; NIH [R01 AG012674, K24 AG026431, P50 AG05131, AG05131, AB005136, AG010129] FX The current study was supported by the Alzheimer's Association (grant IIRG 07-59343 to M. W. B.), and the NIH (grants R01 AG012674 to M. W. B., K24 AG026431 to M. W. B., and P50 AG05131). CSF sample collection was supported by NIH grants AG05131 (UCSD), AB005136 (University of Washington), and AG010129 (Oregon Health Sciences University). NR 10 TC 18 Z9 18 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD DEC 3 PY 2013 VL 81 IS 23 BP 2024 EP 2027 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA AA0FT UT WOS:000330771700013 PM 24225352 ER PT J AU McCauley, M Minsky, S Viswanath, K AF McCauley, Michael Minsky, Sara Viswanath, Kasisomayajula TI The H1N1 pandemic: media frames, stigmatization and coping SO BMC PUBLIC HEALTH LA English DT Article DE H1N1; Communication; Media frames; Latinos; Stigmatization; Stress and coping ID MENTAL-HEALTH STIGMA; INFLUENZA-A H1N1; PSYCHOLOGICAL FLEXIBILITY; COMMITMENT THERAPY; GLOBAL MORTALITY; ACCEPTANCE; IMPACT; ROLES; PERSPECTIVE; ETHNICITY AB Background: Throughout history, people have soothed their fear of disease outbreaks by searching for someone to blame. Such was the case with the April 2009 H1N1 flu outbreak. Mexicans and other Latinos living in the US were quickly stigmatized by non-Latinos as carriers of the virus, partly because of news reports on the outbreak's alleged origin in Mexican pig farms. Methods: In this exploratory study we examined the psychological processes of cue convergence and associative priming, through which many people likely conflated news of the H1N1 outbreak with pre-existing cognitive scripts that blamed Latino immigrants for a variety of social problems. We also used a transactional model of stress and coping to analyze the transcripts from five focus groups, in order to examine the ways in which a diverse collection of New England residents appraised the threat of H1N1, processed information about stereotypes and stigmas, and devised personal strategies to cope with these stressors. Results: Twelve themes emerged in the final wave of coding, with most of them appearing at distinctive points in the stress and coping trajectories of focus group participants. Primary and secondary appraisals were mostly stressful or negative, with participants born in the USA reporting more stressful responses than those who were not. Latino participants reported no stressful primary appraisals, but spoke much more often than Whites or Non-Hispanic Blacks about negative secondary appraisals. When interactions between participants dealt with stigmas regarding Latinos and H1N1, Latinos in our focus groups reported using far more negative coping strategies than Whites or Non-Hispanic Blacks. When discussions did not focus on stereotypes or stigmas, Latino participants spoke much more often about positive coping strategies compared to members of these same groups. Conclusions: Participants in all five focus groups went through a similar process of stress and coping in response to the threat of H1N1, though individual responses varied by race and ethnicity. Stigmatization has often been common during pandemics, and public health and emergency preparedness practitioners can help to mitigate its impacts by developing interventions to address the social stressors that occur during outbreaks in highly-localized geographic regions. C1 [McCauley, Michael] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Minsky, Sara; Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02215 USA. [Minsky, Sara; Viswanath, Kasisomayajula] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02215 USA. RP McCauley, M (reprint author), Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. EM mmccauley@mcw.edu RI McCauley, Michael/C-3642-2014 OI McCauley, Michael/0000-0003-3851-1765 FU Centers for Disease Control and Prevention (CDC) [1P01TP000307-01]; NIH/NCI Harvard Education Program in Cancer Prevention and Control [R25 CA057713]; Dana-Farber Farber/Harvard Cancer Center FX This study was conducted as part of the "Linking Assessment and Measurement to Performance in PHEP Systems" (LAMPS) project funded by the Centers for Disease Control and Prevention (CDC) [#1P01TP000307-01]. Additional support comes from the NIH/NCI Harvard Education Program in Cancer Prevention and Control [R25 CA057713] and the Dana-Farber Farber/Harvard Cancer Center. The authors also acknowledge Divya Ramamurthi, Emily Kontos, Michael Stoto, Elena Savoia and the Mayor's Health Task Force in Lawrence, MA for their contributions to our work. NR 71 TC 4 Z9 4 U1 4 U2 17 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD DEC 3 PY 2013 VL 13 AR 1116 DI 10.1186/1471-2458-13-1116 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 284GU UT WOS:000329304900001 PM 24299568 ER PT J AU Fenton-May, AE Dibben, O Emmerich, T Ding, HT Pfafferott, K Aasa-Chapman, MM Pellegrino, P Williams, I Cohen, MS Gao, F Shaw, GM Hahn, BH Ochsenbauer, C Kappes, JC Borrow, P AF Fenton-May, Angharad E. Dibben, Oliver Emmerich, Tanja Ding, Haitao Pfafferott, Katja Aasa-Chapman, Marlen M. Pellegrino, Pierre Williams, Ian Cohen, Myron S. Gao, Feng Shaw, George M. Hahn, Beatrice H. Ochsenbauer, Christina Kappes, John C. Borrow, Persephone TI Relative resistance of HIV-1 founder viruses to control by interferon-alpha SO RETROVIROLOGY LA English DT Article DE Human immunodeficiency virus type 1; Type 1 interferon; Viral inhibition; Founder virus; Acute infection ID SIMIAN IMMUNODEFICIENCY VIRUS; PERSISTENT LCMV INFECTION; I INTERFERON; GENE-EXPRESSION; REPLICATION CAPACITY; T-CELLS; MUCOSAL TRANSMISSION; REGULATORY FACTOR-3; DISEASE PROGRESSION; VIRAL REPLICATION AB Background: Following mucosal human immunodeficiency virus type 1 (HIV-1) transmission, type 1 interferons (IFNs) are rapidly induced at sites of initial virus replication in the mucosa and draining lymph nodes. However, the role played by IFN-stimulated antiviral activity in restricting HIV-1 replication during the initial stages of infection is not clear. We hypothesized that if type 1 IFNs exert selective pressure on HIV-1 replication in the earliest stages of infection, the founder viruses that succeed in establishing systemic infection would be more IFN-resistant than viruses replicating during chronic infection, when type 1 IFNs are produced at much lower levels. To address this hypothesis, the relative resistance of virus isolates derived from HIV-1-infected individuals during acute and chronic infection to control by type 1 IFNs was analysed. Results: The replication of plasma virus isolates generated from subjects acutely infected with HIV-1 and molecularly cloned founder HIV-1 strains could be reduced but not fully suppressed by type 1 IFNs in vitro. The mean IC50 value for IFNa2 (22 U/ml) was lower than that for IFN beta (346 U/ml), although at maximally-inhibitory concentrations both IFN subtypes inhibited virus replication to similar extents. Individual virus isolates exhibited differential susceptibility to inhibition by IFNa2 and IFN beta, likely reflecting variation in resistance to differentially up-regulated IFN-stimulated genes. Virus isolates from subjects acutely infected with HIV-1 were significantly more resistant to in vitro control by IFNa than virus isolates generated from the same individuals during chronic, asymptomatic infection. Viral IFN resistance declined rapidly after the acute phase of infection: in five subjects, viruses derived from six-month consensus molecular clones were significantly more sensitive to the antiviral effects of IFNs than the corresponding founder viruses. Conclusions: The establishment of systemic HIV-1 infection by relatively IFNa-resistant founder viruses lends strong support to the hypothesis that IFNa plays an important role in the control of HIV-1 replication during the earliest stages of infection, prior to systemic viral spread. These findings suggest that it may be possible to harness the antiviral activity of type 1 IFNs in prophylactic and potentially also therapeutic strategies to combat HIV-1 infection. C1 [Fenton-May, Angharad E.; Dibben, Oliver; Emmerich, Tanja; Pfafferott, Katja; Borrow, Persephone] Univ Oxford, Nuffield Dept Med, Oxford OX3 7FZ, England. [Ding, Haitao; Ochsenbauer, Christina; Kappes, John C.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Aasa-Chapman, Marlen M.] Fac Med, Div Infect & Immun, London, England. [Aasa-Chapman, Marlen M.] Ctr Sexual Hlth & HIV Res, London, England. [Pellegrino, Pierre; Williams, Ian] UCL, Mortimer Market Ctr, Ctr Sexual Hlth & HIV Res, London, England. [Cohen, Myron S.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Gao, Feng] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA. [Gao, Feng] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Shaw, George M.; Hahn, Beatrice H.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Shaw, George M.; Hahn, Beatrice H.] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kappes, John C.] Birmingham Vet Affairs Med Ctr, Res Serv, Birmingham, AL USA. RP Borrow, P (reprint author), Univ Oxford, Nuffield Dept Med, NDM Res Bldg,Old Rd Campus, Oxford OX3 7FZ, England. EM persephone.borrow@ndm.ox.ac.uk OI Fenton-May, Angharad/0000-0002-6267-1315 FU NIH NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI) [U19 AI067854]; NIH NIAID Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) [UM1 AI100645]; UAB CFAR [AI27767]; Edward Jenner Institute for Vaccine Research (PB); Senior Jenner Fellowship; Jenner Institute Investigator FX We are extremely grateful to the patients who provided samples for this study. We would also like to thank Julie Lewis and Elizabeth Marshall for expert technical assistance. This work was supported by funding from the NIH NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI) (U19 AI067854) (FG, GMS, BHH, JCK, PB); the NIH NIAID Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) (UM1 AI100645) (FG, GMS, BHH, JCK, PB); core facilities of the UAB CFAR (AI27767) (JCK); and core funding from The Edward Jenner Institute for Vaccine Research (PB). PB received salary support from a Senior Jenner Fellowship and is a Jenner Institute Investigator. NR 102 TC 66 Z9 67 U1 1 U2 6 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 3 PY 2013 VL 10 AR 146 DI 10.1186/1742-4690-10-146 PG 18 WC Virology SC Virology GA 280RH UT WOS:000329048000001 PM 24299076 ER PT J AU Kansagara, D Dyer, E Englander, H Fu, RW Freeman, M Kagen, D AF Kansagara, Devan Dyer, Edward Englander, Honora Fu, Rongwei Freeman, Michele Kagen, David TI Treatment of Anemia in Patients With Heart Disease A Systematic Review SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID PERCUTANEOUS CORONARY INTERVENTION; ACUTE MYOCARDIAL-INFARCTION; BLOOD-CELL TRANSFUSION; CHRONIC KIDNEY-DISEASE; INTRAVENOUS FERRIC CARBOXYMALTOSE; CLINICAL-PRACTICE GUIDELINE; IRON-DEFICIENCY ANEMIA; QUALITY-OF-LIFE; FAIR-HF TRIAL; DARBEPOETIN-ALPHA AB Background: The benefits of anemia treatment in patients with heart disease are uncertain. Purpose: To evaluate the benefits and harms of treatments for anemia in adults with heart disease. Data Sources: MEDLINE, EMBASE, and Cochrane databases; clinical trial registries; reference lists; and technical advisors. Study Selection: English-language trials of blood transfusions, iron, or erythropoiesis-stimulating agents in adults with anemia and congestive heart failure or coronary heart disease and observational studies of transfusion. Data Extraction: Data on study design, population characteristics, hemoglobin levels, and health outcomes were extracted. Trials were assessed for quality. Data Synthesis: Low-strength evidence from 6 trials and 26 observational studies suggests that liberal transfusion protocols do not improve short-term mortality rates compared with less aggressive protocols (combined relative risk among trials, 0.94 [95% CI, 0.61 to 1.42]; I-2 = 16.8%), although decreased mortality rates occurred in a small trial of patients with the acute coronary syndrome (1.8% vs. 13.0%; P = 0.032). Moderate-strength evidence from 3 trials of intravenous iron found improved short-term exercise tolerance and quality of life in patients with heart failure. Moderate- to high-strength evidence from 17 trials of erythropoiesis-stimulating agent therapy found they offered no consistent benefits, but their use may be associated with harms, such as venous thromboembolism. Limitations: Few trials have examined transfusions in patients with heart disease, and observational studies are potentially confounded by indication. Data supporting iron use come mainly from 1 large trial, and long-term effects are unknown. Conclusion: Higher transfusion thresholds do not consistently improve mortality rates, but large trials are needed. Intravenous iron may help to alleviate symptoms in patients with heart failure and iron deficiency and also warrants further study. Erythropoiesis-stimulating agents do not seem to benefit patients with mild to moderate anemia and heart disease and may be associated with serious harms. C1 [Kansagara, Devan] Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Kansagara, D (reprint author), Portland VA Med Ctr, Mailcode RD71,3710 Southwest US Vet Hosp Rd, Portland, OR 97239 USA. EM kansagar@ohsu.edu FU U.S. Department of Veterans Affairs FX U.S. Department of Veterans Affairs. NR 81 TC 18 Z9 18 U1 0 U2 4 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 3 PY 2013 VL 159 IS 11 BP 746 EP + DI 10.7326/0003-4819-159-11-201312030-00007 PG 18 WC Medicine, General & Internal SC General & Internal Medicine GA 276EN UT WOS:000328731000004 PM 24297191 ER PT J AU Qaseem, A Humphrey, LL Fitterman, N Starkey, M Shekelle, P AF Qaseem, Amir Humphrey, Linda L. Fitterman, Nick Starkey, Melissa Shekelle, Paul CA Amer Coll Phys TI Treatment of Anemia in Patients With Heart Disease: A Clinical Practice Guideline From the American College of Physicians SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID PERCUTANEOUS CORONARY INTERVENTION; ACUTE MYOCARDIAL-INFARCTION; BLOOD-CELL TRANSFUSIONS; DARBEPOETIN-ALPHA; INTRAVENOUS IRON; DOUBLE-BLIND; SUBCUTANEOUS ERYTHROPOIETIN; RESTRICTIVE TRANSFUSION; RENAL-INSUFFICIENCY; EXERCISE TOLERANCE AB Description: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the treatment of anemia and iron deficiency in adult patients with heart disease. Methods: This guideline is based on published literature in the English language on anemia and iron deficiency from 1947 to July 2012 that was identified using MEDLINE and the Cochrane Library. Literature was reassessed in April 2013, and additional studies were included. Outcomes evaluated for this guideline included mortality; hospitalization; exercise tolerance; quality of life; and cardiovascular events (defined as myocardial infarction, congestive heart failure exacerbation, arrhythmia, or cardiac death) and harms, including hypertension, venous thromboembolic events, and ischemic cerebrovascular events. The target audience for this guideline includes all clinicians, and the target patient population is anemic or iron-deficient adult patients with heart disease. This guideline grades the evidence and recommendations using the ACP's clinical practice guidelines grading system. Recommendation 1: ACP recommends using a restrictive red blood cell transfusion strategy (trigger hemoglobin threshold of 7 to 8 g/dL compared with higher hemoglobin levels) in hospitalized patients with coronary heart disease. (Grade: weak recommendation; low-quality evidence) Recommendation 2: ACP recommends against the use of erythropoiesis-stimulating agents in patients with mild to moderate anemia and congestive heart failure or coronary heart disease. (Grade: strong recommendation; moderate-quality evidence) C1 [Qaseem, Amir] Amer Coll Physicians, Philadelphia, PA 19106 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Huntington Hosp, Pasadena, CA USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Qaseem, A (reprint author), Amer Coll Physicians, 190 N Independence Mall West, Philadelphia, PA 19106 USA. EM aqaseem@acponline.org FU ACP FX Financial support for the development of this guideline comes exclusively from the ACP operating budget. NR 66 TC 29 Z9 30 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 3 PY 2013 VL 159 IS 11 BP 770 EP + DI 10.7326/0003-4819-159-11-201312030-00009 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 276EN UT WOS:000328731000006 PM 24297193 ER PT J AU Goodman, DFM Benichoux, V Brette, R AF Goodman, Dan F. M. Benichoux, Victor Brette, Romain TI Decoding neural responses to temporal cues for sound localization SO ELIFE LA English DT Article ID INTERAURAL TIME DIFFERENCES; OWL TYTO-ALBA; MEDIAL SUPERIOR OLIVE; LOW-FREQUENCY NEURONS; INFERIOR COLLICULUS; BARN OWL; SOURCE LOCATION; PRESSURE TRANSFORMATIONS; MERIONES-UNGUICULATUS; POSTNATAL-DEVELOPMENT AB The activity of sensory neural populations carries information about the environment. This may be extracted from neural activity using different strategies. In the auditory brainstem, a recent theory proposes that sound location in the horizontal plane is decoded from the relative summed activity of two populations in each hemisphere, whereas earlier theories hypothesized that the location was decoded from the identity of the most active cells. We tested the performance of various decoders of neural responses in increasingly complex acoustical situations, including spectrum variations, noise, and sound diffraction. We demonstrate that there is insufficient information in the pooled activity of each hemisphere to estimate sound direction in a reliable way consistent with behavior, whereas robust estimates can be obtained from neural activity by taking into account the heterogeneous tuning of cells. These estimates can still be obtained when only contralateral neural responses are used, consistently with unilateral lesion studies. C1 [Goodman, Dan F. M.; Benichoux, Victor; Brette, Romain] CNRS, Lab Psychol Percept, Paris, France. [Goodman, Dan F. M.; Benichoux, Victor; Brette, Romain] Univ Paris 05, Paris, France. [Goodman, Dan F. M.; Benichoux, Victor; Brette, Romain] Ecole Normale Super, Dept Etud Cognit, F-75231 Paris, France. RP Goodman, DFM (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. EM dan_goodman@meei.harvard.edu; romain.brette@ens.fr RI Brette, Romain/I-7120-2016; OI Brette, Romain/0000-0003-0110-1623 FU European Research Council [ERC StG 240132]; Agence Nationale de la Recherche [ANR-11-BSH2-0004, ANR-11-0001-02 PSL*, ANR-10-LABX-0087] FX European Research Council ERC StG 240132 Dan FM Goodman, Victor Benichoux, Romain Brette; Agence Nationale de la Recherche ANR-11-BSH2-0004, ANR-11-0001-02 PSL* and ANR-10-LABX-0087 Dan FM Goodman, Victor Benichoux, Romain Brette NR 68 TC 15 Z9 15 U1 0 U2 11 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD DEC 3 PY 2013 VL 2 AR e01312 DI 10.7554/eLife.01312 PG 21 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 274ZD UT WOS:000328643800004 PM 24302571 ER PT J AU Blacklow, SC AF Blacklow, Stephen C. TI Refining a Jagged Edge SO STRUCTURE LA English DT Editorial Material ID NOTCH; BINDING; PATHWAY C1 [Blacklow, Stephen C.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Blacklow, Stephen C.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Blacklow, Stephen C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Blacklow, SC (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 45 Shattuck St, Boston, MA 02115 USA. EM stephen_blacklow@hms.harvard.edu FU NCI NIH HHS [R01 CA092433, P01 CA119070] NR 10 TC 0 Z9 0 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 EI 1878-4186 J9 STRUCTURE JI Structure PD DEC 3 PY 2013 VL 21 IS 12 BP 2100 EP 2101 DI 10.1016/j.str.2013.11.001 PG 2 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 278UH UT WOS:000328914900003 PM 24315457 ER PT J AU Teo, AKK Wagers, AJ Kulkarni, RN AF Teo, Adrian Kee Keong Wagers, Amy J. Kulkarni, Rohit N. TI New Opportunities: Harnessing Induced Pluripotency for Discovery in Diabetes and Metabolism SO CELL METABOLISM LA English DT Review ID EMBRYONIC STEM-CELLS; HEPATOCYTE NUCLEAR FACTOR-1-ALPHA; TRANSCRIPTION FACTOR KLF11; EARLY-ONSET OBESITY; LONG-QT SYNDROME; MOUSE MODELS; BETA-CELLS; INSULIN-RESISTANCE; SELF-RENEWAL; GLUCOKINASE DEFICIENCY AB The landmark discovery of induced pluripotent stem cells (iPSCs) by Shinya Yamanaka has transformed regenerative biology. Previously, insights into the pathogenesis of chronic human diseases have been hindered by the inaccessibility of patient samples. However, scientists are now able to convert patient fibroblasts into iPSCs and differentiate them into disease-relevant cell types. This ability opens new avenues for investigating disease pathogenesis and designing novel treatments. In this review, we highlight the uses of human iPSCs to uncover the underlying causes and pathological consequences of diabetes and metabolic syndromes, multifactorial diseases whose etiologies have been difficult to unravel using traditional methodologies. C1 [Teo, Adrian Kee Keong; Wagers, Amy J.; Kulkarni, Rohit N.] Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02115 USA. [Teo, Adrian Kee Keong; Wagers, Amy J.; Kulkarni, Rohit N.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Wagers, Amy J.] Harvard Univ, Howard Hughes Med Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Wagers, Amy J.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Wagers, Amy J.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Kulkarni, RN (reprint author), Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, 75 Francis St, Boston, MA 02115 USA. EM rohit.kulkarni@joslin.harvard.edu RI Teo, Adrian/A-4009-2013 OI Teo, Adrian/0000-0001-5901-7075 FU Juvenile Diabetes Research Foundation Postdoctoral Fellowship; National Institute of Health [RO1 DK 67536, RO1 DK 055523]; Harvard Stem Cell Institute; JDRF/Sanofi Strategic Alliance Grant; Astra Zeneca; Diabetes Research Center grant [NIH P30DK036836] FX The authors would like to thank Julia Li for assistance with the graphics and apologize to all those whose work was not discussed and cited due to space constraints. A. K. K. T. is supported by a Juvenile Diabetes Research Foundation Postdoctoral Fellowship. R.N.K. is supported by National Institute of Health grants RO1 DK 67536 and RO1 DK 055523, the Harvard Stem Cell Institute, a JDRF/Sanofi Strategic Alliance Grant, and a grant from the Astra Zeneca. This work was also supported by a Diabetes Research Center grant (NIH P30DK036836) to the Joslin Diabetes Center. The authors declare no conflicts of interest. NR 169 TC 11 Z9 11 U1 1 U2 19 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD DEC 3 PY 2013 VL 18 IS 6 BP 775 EP 791 DI 10.1016/j.cmet.2013.08.010 PG 17 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 265HJ UT WOS:000327940800005 PM 24035588 ER PT J AU Greenblatt, MB Ritter, SY Wright, J Tsang, K Hu, D Glimcher, LH Aliprantis, AO AF Greenblatt, Matthew B. Ritter, Susan Y. Wright, John Tsang, Kelly Hu, Dorothy Glimcher, Laurie H. Aliprantis, Antonios O. TI NFATc1 and NFATc2 repress spontaneous osteoarthritis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRANSCRIPTION FACTOR; PATELLAR DISLOCATION; ARTICULAR-CARTILAGE; IN-VITRO; MOUSE; JOINT; MICE; DIFFERENTIATION; CHONDROCYTES; BONE AB Osteoarthritis (OA) was once viewed originally as a mechanical disease of "wear and tear," but advances made during the past two decades suggest that abnormal biomechanics contribute to active dysregulation of chondrocyte biology, leading to catabolism of the cartilage matrix. A number of signaling and transcriptional mechanisms have been studied in relation to the regulation of this catabolic program, but how they specifically regulate the initiation or progression of the disease is poorly understood. Here, we demonstrate that cartilage-specific ablation of Nuclear factor of activated T cells c1 (Nfatc1) in Nfatc2(-/-) mice leads to early onset, aggressive OA affecting multiple joints. This model recapitulates features of human OA, including loss of proteoglycans, collagen and aggrecan degradation, osteophyte formation, changes to subchondral bone architecture, and eventual progression to cartilage effacement and joint instability. Consistent with the notion that NFATC1 is an OA-suppressor gene, NFATC1 expression was significantly down-regulated in paired lesional vs. macroscopically normal cartilage samples from OA patients. The highly penetrant, early onset, and severe nature of this model make it an attractive platform for the preclinical development of treatments to alter the course of OA. Furthermore, these findings indicate that NFATs are key suppressors of OA, and regulating NFATs or their transcriptional targets in chondrocytes may lead to novel disease-modifying OA therapies. C1 [Greenblatt, Matthew B.] Brigham & Womens Hosp, Dept Pathol, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Ritter, Susan Y.; Tsang, Kelly; Aliprantis, Antonios O.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Wright, John] Brigham & Womens Hosp, Dept Orthoped, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hu, Dorothy] Massachusetts Gen Hosp, Div Endocrinol, Boston, MA 02114 USA. [Glimcher, Laurie H.] Weill Cornell Med Coll, New York, NY 10065 USA. RP Glimcher, LH (reprint author), Weill Cornell Med Coll, New York, NY 10065 USA. EM lglimche@med.cornell.edu; aaliprantis@partners.org FU Arthritis Foundation; Career Award for Medical Scientists from the Burroughs Wellcome Fund; National Institutes of Health [K08AR054859, R01AR060363-01] FX This work was supported by an Arthritis Foundation grant (to L.H.G.), a Career Award for Medical Scientists from the Burroughs Wellcome Fund (to A.O.A.), and by National Institutes of Health Grants K08AR054859 (to A.O.A) and R01AR060363-01 (to A.O.A.). NR 58 TC 19 Z9 20 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 3 PY 2013 VL 110 IS 49 BP 19914 EP 19919 DI 10.1073/pnas.1320036110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 262OJ UT WOS:000327744900061 PM 24248346 ER PT J AU Arbustini, E Narula, N Dec, GW Reddy, KS Greenberg, B Kushwaha, S Marwick, T Pinney, S Bellazzi, R Favalli, V Kramer, C Roberts, R Zoghbi, WA Bonow, R Tavazzi, L Fuster, V Narula, J AF Arbustini, Eloisa Narula, Navneet Dec, G. William Reddy, K. Srinath Greenberg, Barry Kushwaha, Sudhir Marwick, Thomas Pinney, Sean Bellazzi, Riccardo Favalli, Valentina Kramer, Christopher Roberts, Robert Zoghbi, William A. Bonow, Robert Tavazzi, Luigi Fuster, Valentin Narula, Jagat TI The MOGE(S) Classification for a Phenotype-Genotype Nomenclature of Cardiomyopathy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE cardiomyopathy; diastolic dysfunction; heart failure; heart muscle disease; myocardial hypertrophy; systolic dysfunction ventricular arrhythmias ID IDIOPATHIC DILATED CARDIOMYOPATHY; RIGHT-VENTRICULAR CARDIOMYOPATHY; BETA-GALACTOSIDASE DEFICIENCY; PRIMARY CARNITINE DEFICIENCY; CARDIOLOGY WORKING GROUP; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY; PERICARDIAL DISEASES; CARDIAC AMYLOIDOSIS; POSITION STATEMENT C1 [Arbustini, Eloisa; Favalli, Valentina] Ctr Inherited Cardiovasc Dis, Pavia, Italy. [Narula, Navneet] New York Presbyterian Hosp, Weill Cornell Med Coll, Dept Pathol, New York, NY USA. [Dec, G. William] Massachusetts Gen Hosp, Cardiol Div, Boston, MA 02114 USA. [Reddy, K. Srinath] Publ Hlth Fdn India, New Delhi, India. [Greenberg, Barry] Univ Calif San Diego, San Diego, CA 92103 USA. [Kushwaha, Sudhir] Mayo Clin, Coll Med, Rochester, MN USA. [Marwick, Thomas] Univ Queensland, Princess Alexandra Hosp, Brisbane, Qld 4072, Australia. [Pinney, Sean; Fuster, Valentin; Narula, Jagat] Mt Sinai Med Ctr, New York, NY 10029 USA. [Bellazzi, Riccardo] Univ Pavia, Dept Ind & Informat Engn, I-27100 Pavia, Italy. [Kramer, Christopher] Univ Virginia, Charlottesville, VA USA. [Roberts, Robert] Univ Ottawa, Inst Heart, John & Jennifer Ruddy Canadian Cardiovasc Res Ctr, Ottawa, ON, Canada. [Zoghbi, William A.] Methodist Hosp, Methodist DeBakey Heart & Vasc Ctr, Houston, TX 77030 USA. [Bonow, Robert] Ctr Cardiovasc Innovat, Chicago, IL USA. [Tavazzi, Luigi] Hlth Sci Fdn, ES, GVM Care & Res, Maria Cecilia Hosp, Cotignola, Italy. RP Narula, J (reprint author), Icahn Sch Med Mt Sinai, Zena & Michael A Weiner Cardiovasc Inst, 1 Gustave L Levy Pl,Box 1030, New York, NY 10029 USA. EM narula@mountsinai.org RI Fuster, Valentin/H-4319-2015; OI Fuster, Valentin/0000-0002-9043-9986; Favalli, Valentina/0000-0002-7058-6479 FU European Union INHERITANCE project [241924]; Italian Ministry of Health "Diagnosis and Treatment of Hypertrophic Cardiomyopathies" [RF-PSM-2008-1145809]; GE Healthcare and Phillips; Novartis; Siemens Healthcare FX Maria Cecilia Hospital, GVM Care & Research, E. S, Health Science Foundation, Cotignola, Italy. This study was supported by Grants European Union INHERITANCE project no 241924 and Italian Ministry of Health "Diagnosis and Treatment of Hypertrophic Cardiomyopathies" (no RF-PSM-2008-1145809) to EA, IRCCS Policlinico San Matteo, Pavia. Dr. Greenberg is a consultant for Zensun, Celladon, Mesoblast, Novartis, and Teva Pharmaceutical; and is on the Speakers' Bureaus of Otsuka and Boehringer Ingelheim. Dr. Kramer has received research support from Novartis (research funding) and Siemens Healthcare (equipment); and is a consultant for Synarc and St. Jude Medical. Dr. J. Narula has received research grants from GE Healthcare and Phillips. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 92 TC 34 Z9 37 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 3 PY 2013 VL 62 IS 22 BP 2046 EP 2072 DI 10.1016/j.jacc.2013.08.1644 PG 27 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 259NK UT WOS:000327533400003 PM 24263073 ER PT J AU Wimmer, NJ Resnic, FS Mauri, L Matheny, ME Yeh, RW AF Wimmer, Neil J. Resnic, Frederic S. Mauri, Laura Matheny, Michael E. Yeh, Robert W. TI Comparison of Transradial Versus Transfemoral Percutaneous Coronary Intervention in Routine Practice Evidence for the Importance of "Falsification Hypotheses" in Observational Studies of Comparative Effectiveness SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Letter ID CARDIOVASCULAR DATA REGISTRY C1 [Wimmer, Neil J.; Mauri, Laura] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Resnic, Frederic S.] Lahey Clin Fdn, Burlington, MA USA. [Matheny, Michael E.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Yeh, Robert W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Yeh, RW (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St GRB 800, Boston, MA 02114 USA. EM ryeh@partners.org OI Matheny, Michael/0000-0003-3217-4147 FU NHLBI NIH HHS [T32-HL00760] NR 5 TC 11 Z9 11 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 3 PY 2013 VL 62 IS 22 BP 2147 EP 2148 DI 10.1016/j.jacc.2013.07.036 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 259NK UT WOS:000327533400019 PM 23954334 ER PT J AU Ferguson, AL Falkowska, E Walker, LM Seaman, MS Burton, DR Chakraborty, AK AF Ferguson, Andrew L. Falkowska, Emilia Walker, Laura M. Seaman, Michael S. Burton, Dennis R. Chakraborty, Arup K. TI Computational Prediction of Broadly Neutralizing HIV-1 Antibody Epitopes from Neutralization Activity Data SO PLOS ONE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; B-CELL EPITOPES; GP120 ENVELOPE GLYCOPROTEIN; MONOCLONAL-ANTIBODIES; MUTUAL INFORMATION; BINDING-AFFINITY; PEPTIDE BINDING; IN-VITRO; VACCINE; PROTECTION AB Broadly neutralizing monoclonal antibodies effective against the majority of circulating isolates of HIV-1 have been isolated from a small number of infected individuals. Definition of the conformational epitopes on the HIV spike to which these antibodies bind is of great value in defining targets for vaccine and drug design. Drawing on techniques from compressed sensing and information theory, we developed a computational methodology to predict key residues constituting the conformational epitopes on the viral spike from cross-clade neutralization activity data. Our approach does not require the availability of structural information for either the antibody or antigen. Predictions of the conformational epitopes of ten broadly neutralizing HIV-1 antibodies are shown to be in good agreement with new and existing experimental data. Our findings suggest that our approach offers a means to accelerate epitope identification for diverse pathogenic antigens. C1 [Ferguson, Andrew L.] Univ Illinois, Dept Mat Sci & Engn, Urbana, IL USA. [Falkowska, Emilia; Burton, Dennis R.; Chakraborty, Arup K.] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. [Falkowska, Emilia; Burton, Dennis R.; Chakraborty, Arup K.] Harvard Univ, Boston, MA 02115 USA. [Falkowska, Emilia; Walker, Laura M.; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Falkowska, Emilia; Walker, Laura M.; Burton, Dennis R.] Scripps Res Inst, Int AIDS Vaccine Initiat, Neutralizing Antibody Ctr, La Jolla, CA 92037 USA. [Falkowska, Emilia; Walker, Laura M.; Burton, Dennis R.] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Design, La Jolla, CA 92037 USA. [Seaman, Michael S.] Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. [Chakraborty, Arup K.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Chakraborty, Arup K.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Chakraborty, Arup K.] MIT, Dept Phys, Cambridge, MA 02139 USA. [Chakraborty, Arup K.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. RP Chakraborty, AK (reprint author), MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. EM arupc@mit.edu OI Ferguson, Andrew/0000-0002-8829-9726 FU Ragon Institute; National Institutes of Health; Ragon Postdoctoral Fellowship FX Financial support for this work was provided by the Ragon Institute (A. K. C.; http://www.ragoninstitute.org), a National Institutes of Health Director's Pioneers Award (A. K. C.; https://commonfund.nih.gov/pioneer), and a Ragon Postdoctoral Fellowship (A. L. F.; http://www.ragoninstitute.org). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 79 TC 5 Z9 5 U1 0 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 2 PY 2013 VL 8 IS 12 AR e80562 DI 10.1371/journal.pone.0080562 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 265IN UT WOS:000327944500029 PM 24312481 ER PT J AU Liu, D Liu, CX Li, JQ Azadzoi, K Yang, Y Fei, Z Dou, KF Kowall, NW Choi, HP Vieira, F Yang, JH AF Liu, Dong Liu, Chaoxu Li, Junqiang Azadzoi, Kazem Yang, Yun Fei, Zhou Dou, Kefeng Kowall, Neil W. Choi, Han-Pil Vieira, Fernando Yang, Jing-Hua TI Proteomic Analysis Reveals Differentially Regulated Protein Acetylation in Human Amyotrophic Lateral Sclerosis Spinal Cord SO PLOS ONE LA English DT Article ID MOTOR-NEURON DEGENERATION; TRANSGENIC MOUSE MODEL; ALS-LINKED SOD1; AGGREGATE FORMATION; OXIDATIVE STRESS; DISEASE; NEURODEGENERATION; UBIQUITINATION; ASTROCYTES; DISMUTASE AB Amyotrophic lateral sclerosis (ALS) is a progressive fatal neurodegenerative disease that primarily affects motor neurons in the brain and spinal cord. Histone deacetylase (HDAC) inhibitors have neuroprotective effects potentially useful for the treatment of neurodegenerative diseases including ALS; however, the molecular mechanisms underlying their potential efficacy is not well understood. Here we report that protein acetylation in urea-soluble proteins is differently regulated in post-mortem ALS spinal cord. Two-dimensional electrophoresis (2-DE) analysis reveals several protein clusters with similar molecular weight but different charge status. Liquid chromatography and tandem mass spectrometry (LC-MS/MS) identifies glial fibrillary acidic protein (GFAP) as the dominant component in the protein clusters. Further analysis indicates six heavily acetylated lysine residues at positions 89, 153, 189, 218, 259 and 331 of GFAP. Immunoprecipitation followed by Western blotting confirms that the larger form of GFAP fragments are acetylated and upregulated in ALS spinal cord. Further studies demonstrate that acetylation of the proteins additional to GFAP is differently regulated, suggesting that acetylation and/or deacetylation play an important role in pathogenesis of ALS. C1 [Liu, Dong; Liu, Chaoxu; Azadzoi, Kazem; Yang, Yun; Kowall, Neil W.; Yang, Jing-Hua] VA Boston Healthcare Syst, Dept Surg, Dept Neurol, Boston, MA USA. [Liu, Dong; Liu, Chaoxu; Azadzoi, Kazem; Yang, Yun; Kowall, Neil W.; Yang, Jing-Hua] VA Boston Healthcare Syst, Dept Urol, Boston, MA USA. [Liu, Dong; Liu, Chaoxu; Azadzoi, Kazem; Yang, Yun; Kowall, Neil W.; Choi, Han-Pil; Yang, Jing-Hua] Boston Univ, Sch Med, Boston, MA 02118 USA. [Li, Junqiang; Yang, Jing-Hua] Shandong Univ, Sch Med, Canc Res Ctr, Jinan 250100, Shandong, Peoples R China. [Choi, Han-Pil; Yang, Jing-Hua] VA Boston Healthcare Syst, Prote Facil, Boston, MA USA. [Vieira, Fernando] ALS Therapy Dev Inst, Cambridge, MA USA. RP Yang, JH (reprint author), VA Boston Healthcare Syst, Dept Surg, Dept Neurol, Boston, MA USA. EM jyang@bu.edu RI Kowall, Neil/G-6364-2012; OI Kowall, Neil/0000-0002-6624-0213; Vieira, Fernando/0000-0003-2996-6418 FU National Institutes of Health [K02-AI-060701, AG013846]; Shandong University; Department of Veterans Affairs Biorepository FX The study is supported by grants from the National Institutes of Health to J.-H. Yang (K02-AI-060701) and N. Kowall (AG013846), and financial support from Shandong University to J.-H. Yang and the Department of Veterans Affairs Biorepository to N. Kowall and K. Azadzoi. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 6 Z9 6 U1 1 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 2 PY 2013 VL 8 IS 12 AR e80779 DI 10.1371/journal.pone.0080779 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 265IN UT WOS:000327944500042 PM 24312501 ER PT J AU Politi, MC Dizon, DS Frosch, DL Kuzemchak, MD Stiggelbout, AM AF Politi, Mary C. Dizon, Don S. Frosch, Dominick L. Kuzemchak, Marie D. Stiggelbout, Anne M. TI Importance of clarifying patients' desired role in shared decision making to match their level of engagement with their preferences SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID BREAST-CANCER; PHYSICIANS PERCEPTIONS; SUPPORT INTERVENTIONS; HEALTH-PROFESSIONALS; CLINICAL-PRACTICE; PATIENTS WANT; INVOLVEMENT; INFORMATION; PARTICIPATION; DIFFICULT C1 [Politi, Mary C.; Kuzemchak, Marie D.] Washington Univ, Sch Med, Div Publ Hlth Sci, Dept Surg, St Louis, MO 63112 USA. [Dizon, Don S.] Massachusetts Gen Hosp, Ctr Canc, Gillette Ctr Gynecol Oncol, Boston, MA USA. [Dizon, Don S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Frosch, Dominick L.] Gordon & Betty Moore Fdn, Patient Care Program, Palo Alto, CA USA. [Frosch, Dominick L.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Frosch, Dominick L.] Palo Alto Med Fdn, Res Inst, Palo Alto, CA 94301 USA. [Stiggelbout, Anne M.] Leiden Univ, Med Ctr, Dept Med Decis Making, Leiden, Netherlands. RP Politi, MC (reprint author), Washington Univ, Sch Med, Div Publ Hlth Sci, Dept Surg, 660 South Euclid Ave,Campus Box 8100, St Louis, MO 63112 USA. EM mpoliti@wustl.edu OI Politi, Mary/0000-0001-9103-6495 NR 38 TC 19 Z9 19 U1 2 U2 12 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BMJ-BRIT MED J JI BMJ-British Medical Journal PD DEC 2 PY 2013 VL 347 AR F7066 DI 10.1136/bmj.f7066 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 268CV UT WOS:000328146700003 PM 24297974 ER PT J AU Xie, ZC Xu, ZP AF Xie, Zhongcong Xu, Zhipeng TI General anesthetics and beta-amyloid protein SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE General anesthetics; beta-Amyloid protein; Neurotoxicity ID INSULIN-DEGRADING ENZYME; ISOFLURANE INDUCES APOPTOSIS; INDUCED CASPASE-3 ACTIVATION; GAMMA-SECRETASE ACTIVITY; ALZHEIMERS-DISEASE; PRECURSOR PROTEIN; RAT-BRAIN; VOLATILE ANESTHETICS; NEURONAL APOPTOSIS; COGNITIVE DECLINE AB With roughly 234 million people undergoing surgery with anesthesia each year worldwide, it is important to determine whether commonly used anesthetics can induce any neurotoxicity. Alzheimer's disease (AD) is the most common form of age-related dementia, and a rapidly growing health problem. Several studies suggest that anesthesia could be associated with the development of AD. Moreover, studies in cultured cells and animals show that commonly used inhalation anesthetics may induce changes consistent with AD neuropathogenesis, e.g., beta-amyloid protein accumulation. Therefore, in this mini review, we focus on the recent research investigating the effects of commonly used anesthetics including isoflurane, sevoflurane, desflurane, nitrous oxide, and propofol, on A beta accumulation in vitro and in vivo. We further discuss the future direction of the research determining the effects of anesthetics on beta-amyloid protein accumulation. (C) 2012 Elsevier Inc. All rights reserved. C1 [Xie, Zhongcong] Massachusetts Gen Hosp, Geriatr Anesthesia Res Unit, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA 02129 USA. [Xie, Zhongcong] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Xie, ZC (reprint author), Massachusetts Gen Hosp, Geriatr Anesthesia Res Unit, Dept Anesthesia Crit Care & Pain Med, 149 13th St,Room 4310, Charlestown, MA 02129 USA. EM zxie@partners.org FU National Institutes of Health, Bethesda, Maryland [R21AG029856, R21AG038994, R01 GM088801]; Cure Alzheimer's Fund, Wellesley, Massachusetts FX This research was supported by R21AG029856, R21AG038994 and R01 GM088801 from National Institutes of Health, Bethesda, Maryland, and from Cure Alzheimer's Fund, Wellesley, Massachusetts to Zhongcong Xie. NR 85 TC 12 Z9 15 U1 2 U2 25 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD DEC 2 PY 2013 VL 47 BP 140 EP 146 DI 10.1016/j.pnpbp.2012.08.002 PG 7 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 248FX UT WOS:000326682300023 PM 22918033 ER PT J AU Mannstadt, M Clarke, BL Vokes, T Brandi, ML Ranganath, L Fraser, WD Lakatos, P Bajnok, L Garceau, R Mosekilde, L Lagast, H Shoback, D Bilezikian, JP AF Mannstadt, Michael Clarke, Bart L. Vokes, Tamara Brandi, Maria Luisa Ranganath, Lakshminarayan Fraser, William D. Lakatos, Peter Bajnok, Laszlo Garceau, Roger Mosekilde, Leif Lagast, Hjalmar Shoback, Dolores Bilezikian, John P. TI Efficacy and safety of recombinant human parathyroid hormone (1-84) in hypoparathyroidism (REPLACE): a double-blind, placebo-controlled, randomised, phase 3 study SO LANCET DIABETES & ENDOCRINOLOGY LA English DT Article ID LONG-TERM TREATMENT; CROSSOVER TRIAL; THERAPY; PTH(1-84); CALCIUM; CALCITRIOL; PARATHYROID-HORMONE-1-34; CHILDREN AB Background Hypoparathyroidism results in impaired mineral homoeostasis, including hypocalcaemia and hyperphosphataemia. Treatment with high-dose oral calcium and active vitamin D does not provide adequate or consistent control of biochemical indices and can lead to serious long-term complications. We aimed to test the efficacy, safety, and tolerability of once-daily recombinant human parathyroid hormone 1-84 (rhPTH[1-84]) in adults with hypoparathyroidism. Methods In this double-blind, placebo-controlled, randomised phase 3 study (REPLACE), we recruited patients with hypoparathyroidism (>= 18 months duration) aged 18-85 years from 33 sites in eight countries. After an optimisation period, during which calcium and active vitamin D doses were adjusted to achieve consistent albumin-corrected serum calcium, patients were randomly assigned (2: 1) via an interactive voice response system to 50 mu g per day of rhPTH(1-84) or placebo for 24 weeks. Active vitamin D and calcium were progressively reduced, while rhPTH(1-84) could be titrated up from 50 mu g to 75 mu g and then 100 g (weeks 0-5). The primary endpoint was the proportion of patients at week 24 who achieved a 50% or greater reduction from baseline in their daily dose of oral calcium and active vitamin D while maintaining a serum calcium concentration greater than or the same as baseline concentrations and less than or equal to the upper limit of normal, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00732615. Findings Between June 23, 2009, and Feb 28, 2011, 134 eligible patients were recruited and randomly assigned to rhPTH(1-84) (n=90) or placebo (n=44). Six patients in the rhPTH(1-84) group and seven in the placebo group discontinued before study end. 48 (53%) patients in the rhPTH(1-84) group achieved the primary endpoint compared with one (2%) patient in the placebo group (percentage difference 51.1%, 95% CI 39.9-62.3; p<0.0001). The proportions of patients who had at least one adverse event were similar between groups (84 [93%] patients in the rhPTH[1-84] group vs 44 [100%] patients in the placebo group), with hypocalcaemia, muscle spasm, paraesthesias, headache, and nausea being the most common adverse events. The proportions of patients with serious adverse events were also similar between the rhPTH(1-84) group (ten [11%] patients) and the placebo group (four [9%] patients). Interpretation 50 mu g, 75 mu g, or 100 mu g per day of rhPTH(1-84), administered subcutaneously in the outpatient setting, is efficacious and well tolerated as a PTH replacement therapy for patients with hypoparathyroidism. C1 [Mannstadt, Michael] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA USA. [Clarke, Bart L.] Mayo Clin, Div Endocrinol Diabet Metab & Nutr, Rochester, MN USA. [Vokes, Tamara] Univ Chicago Med, Endocrinol Sect, Chicago, IL USA. [Brandi, Maria Luisa] Univ Florence, Dept Internal Med, Florence, Italy. [Ranganath, Lakshminarayan] Royal Liverpool Univ Hosp, Dept Clin Biochem & Metab Med, Liverpool, Merseyside, England. [Fraser, William D.] Univ E Anglia, Norwich Med Sch, Dept Med, Norwich NR4 7TJ, Norfolk, England. [Lakatos, Peter] Semmelweis Univ, Dept Internal Med 1, H-1085 Budapest, Hungary. [Bajnok, Laszlo] Univ Pecs, Sch Med, Dept Internal Med 1, Pecs, Hungary. [Garceau, Roger; Lagast, Hjalmar] NPS Pharmaceut, Bedminster, NJ USA. [Mosekilde, Leif] Aarhus Univ Hosp, Dept Endocrinol & Internal Med, DK-8000 Aarhus, Denmark. [Shoback, Dolores] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Endocrine Res Unit, San Francisco, CA 94143 USA. [Bilezikian, John P.] Columbia Univ, Coll Phys & Surg, Div Endocrinol, New York, NY USA. RP Mannstadt, M (reprint author), Massachusetts Gen Hosp, Endocrine Unit Thier 1051, Boston, MA 02114 USA. EM mmannstadt@partners.org FU NPS Pharmaceuticals FX NPS Pharmaceuticals. NR 22 TC 41 Z9 42 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2213-8587 J9 LANCET DIABETES ENDO JI Lancet Diabetes Endocrinol. PD DEC PY 2013 VL 1 IS 4 BP 275 EP 283 DI 10.1016/S2213-8587(13)70106-2 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP1AV UT WOS:000341799700012 PM 24622413 ER PT J AU Rigby, MR DiMeglio, LA Rendell, MS Felner, EI Dostou, JM Gitelman, SE Patel, CM Griffin, KJ Tsalikian, E Gottlieb, PA Greenbaum, CJ Sherry, NA Moore, WV Monzavi, R Willi, SM Raskin, P Moran, A Russell, WE Pinckney, A Keyes-Elstein, L Howell, M Aggarwal, S Lim, N Phippard, D Nepom, GT McNamara, J Ehlers, MR AF Rigby, Mark R. DiMeglio, Linda A. Rendell, Marc S. Felner, Eric I. Dostou, Jean M. Gitelman, Stephen E. Patel, Chetanbabu M. Griffin, Kurt J. Tsalikian, Eva Gottlieb, Peter A. Greenbaum, Carla J. Sherry, Nicole A. Moore, Wayne V. Monzavi, Roshanak Willi, Steven M. Raskin, Philip Moran, Antoinette Russell, William E. Pinckney, Ashley Keyes-Elstein, Lynette Howell, Michael Aggarwal, Sudeepta Lim, Noha Phippard, Deborah Nepom, Gerald T. McNamara, James Ehlers, Mario R. CA T1DAL Study Team TI Targeting of memory T cells with alefacept in new-onset type 1 diabetes (T1DAL study): 12 month results of a randomised, double-blind, placebo-controlled phase 2 trial SO LANCET DIABETES & ENDOCRINOLOGY LA English DT Article ID CHRONIC PLAQUE PSORIASIS; C-PEPTIDE; THERAPY; PRESERVATION; MULTICENTER; TEPLIZUMAB; RESPONSES AB Background Type 1 diabetes results from autoimmune targeting of the pancreatic beta cells, likely mediated by effector memory T (Tem) cells. CD2, a T cell surface protein highly expressed on Tem cells, is targeted by the fusion protein alefacept, depleting Tem cells and central memory T (Tcm) cells. We postulated that alefacept would arrest autoimmunity and preserve residual beta cells in patients newly diagnosed with type 1 diabetes. Methods The T1DAL study is a phase 2, double-blind, placebo-controlled trial in patients with type 1 diabetes, aged 12-35 years who, within 100 days of diagnosis, were enrolled at 14 US sites. Patients were randomly assigned (2: 1) to receive alefacept (two 12-week courses of 15 mg intramuscularly per week, separated by a 12-week pause) or a placebo. Randomisation was stratified by site, and was computer-generated with permuted blocks of three patients per block. All participants and site personnel were masked to treatment assignment. The primary endpoint was the change from baseline in mean 2 h C-peptide area under the curve (AUC) at 12 months. Secondary endpoints at 12 months were the change from baseline in the 4 h C-peptide AUC, insulin use, major hypoglycaemic events, and HbA(1c) concentrations. This trial is registered with ClinicalTrials.gov, number NCT00965458. Findings Of 73 patients assessed for eligibility, 33 were randomly assigned to receive alefacept and 16 to receive placebo. The mean 2 h C-peptide AUC at 12 months increased by 0.015 nmol/L (95% CI-0.080 to 0.110) in the alefacept group and decreased by 0 115 nmol/L (-0.278 to 0.047) in the placebo group, and the difference between groups was not significant (p=0.065). However, key secondary endpoints were met: the mean 4 h C-peptide AUC was significantly higher (mean increase of 0.015 nmol/L [95% CI-0.076 to 0.106] vs decrease of -0.156 nmol/L [-0.305 to -0.006]; p=0.019), and daily insulin use (0.48 units per kg per day for placebo vs 0.36 units per kg per day for alefacept; p= 0.02) and the rate of hypoglycaemic events (mean of 10.9 events per person per year for alefacept vs 17.3 events for placebo; p< 0.0001) was significantly lower at 12 months in the alefacept group than in the placebo group. Mean HbA(1c) concentrations at week 52 were not different between treatment groups (p=0.75). So far, no serious adverse events were reported and all patients had at least one adverse event. In the alefacept group, 29 (88%) participants had an adverse event related to study drug versus 15 (94%) participants in the placebo group. In the alefacept group, 14 (42%) participants had grade 3 or 4 adverse events compared with nine (56%) participants in the placebo group; no deaths occurred. Interpretation Although the primary outcome was not met, at 12 months, alefacept preserved the 4 h C-peptide AUC, lowered insulin use, and reduced hypoglycaemic events, suggesting efficacy. Safety and tolerability were similar in the alefacept and placebo groups. Alefacept could be useful to preserve beta-cell function in patients with new-onset type 1 diabetes. C1 [Rigby, Mark R.; DiMeglio, Linda A.] Indiana Univ, Indianapolis, IN 46204 USA. [Rigby, Mark R.; DiMeglio, Linda A.] Indiana Univ Hlth, Riley Hosp Children, Indianapolis, IN USA. [Rendell, Marc S.] Creighton Diabet Ctr, Omaha, NE USA. [Felner, Eric I.] Emory Univ, Atlanta, GA 30322 USA. [Dostou, Jean M.] Univ N Carolina, Durham, NC USA. [Gitelman, Stephen E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Patel, Chetanbabu M.; Griffin, Kurt J.] Univ Arizona, Tucson, AZ USA. [Tsalikian, Eva] Univ Iowa, Iowa City, IA USA. [Gottlieb, Peter A.] Univ Colorado, Barbara Davis Ctr, Aurora, CO USA. [Greenbaum, Carla J.; Nepom, Gerald T.] Benaroya Res Inst, Seattle, WA USA. [Sherry, Nicole A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Moore, Wayne V.] Childrens Mercy Hosp, Kansas City, MO 64108 USA. [Monzavi, Roshanak] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Willi, Steven M.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Raskin, Philip] Univ Texas Dallas, SW Med Ctr, Dallas, TX USA. [Moran, Antoinette] Univ Minnesota, Minneapolis, MN USA. [Russell, William E.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Pinckney, Ashley; Keyes-Elstein, Lynette] Fed Syst Div, Chapel Hill, NC USA. [Howell, Michael; Aggarwal, Sudeepta; Lim, Noha; Phippard, Deborah; Ehlers, Mario R.] Immune Tolerance Network, Bethesda, MD USA. [McNamara, James] NIAID, Bethesda, MD 20892 USA. RP Rigby, MR (reprint author), Indiana Hosp, 705 Riley Hosp Dr,ROC 4270, Indianapolis, IN 46202 USA. EM mrigby@iu.edu OI DiMeglio, Linda/0000-0002-8033-6078; Nepom, Gerald/0000-0002-8063-1464 FU US National Institutes of Health; Juvenile Diabetes Research Foundation FX US National Institutes of Health and the Juvenile Diabetes Research Foundation NR 29 TC 54 Z9 54 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2213-8587 J9 LANCET DIABETES ENDO JI Lancet Diabetes Endocrinol. PD DEC PY 2013 VL 1 IS 4 BP 284 EP 294 DI 10.1016/S2213-8587(13)70111-6 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP1AV UT WOS:000341799700013 PM 24622414 ER PT J AU Sandoval, GJ Graham, DB Gmyrek, GB Akilesh, HM Fujikawa, K Sammut, B Bhattacharya, D Srivatsan, S Kim, A Shaw, AS Yang-Iott, K Bassing, CH Duncavage, E Xavier, RJ Swat, W AF Sandoval, Gabriel J. Graham, Daniel B. Gmyrek, Grzegorz B. Akilesh, Holly M. Fujikawa, Keiko Sammut, Benedicte Bhattacharya, Deepta Srivatsan, Shuba Kim, Alfred Shaw, Andrey S. Yang-Iott, Katherine Bassing, Craig H. Duncavage, Eric Xavier, Ramnik J. Swat, Wojciech TI Novel Mechanism of Tumor Suppression by Polarity Gene Discs Large 1 (DLG1) Revealed in a Murine Model of Pediatric B-ALL SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; LIGHT-CHAIN RECOMBINATION; BRUTONS TYROSINE KINASE; DNA-BINDING ACTIVITY; T-CELL-RECEPTOR; LYMPHOCYTE DEVELOPMENT; PRO-B; SLP-65; PROTEINS; PTEN AB Drosophila melanogaster discs large (dlg) is an essential tumor suppressor gene (TSG) controlling epithelial cell growth and polarity of the fly imaginal discs in pupal development. A mammalian ortholog, Dlg1, is involved in embryonic urogenital morphogenesis, postsynaptic densities in neurons, and immune synapses in lymphocytes. However, a potential role for Dlg1 as a mammalian TSG is unknown. Here, we present evidence that loss of Dlg1 confers strong predisposition to the development of malignancies in a murine model of pediatric B-cell acute lymphoblastic leukemia (B-ALL). Using mice with conditionally deleted Dlg1 alleles, we identify a novel "preleukemic" stage of developmentally arrested early B-lineage cells marked by preeminent c-Myc expression. Mechanistically, we show that in B-lineage progenitors Dlg1 interacts with and stabilizes the PTEN protein, regulating its half-life and steady-state abundance. The loss of Dlg1 does not affect the level of PTEN mRNAs but results in a dramatic decrease in PTEN protein, leading to excessive phosphoinositide 3-kinase signaling and proliferation. Our data suggest a novel model of tumor suppression by a PDZ domain-containing polarity gene in hematopoietic cancers. (C) 2013 AACR. C1 [Sandoval, Gabriel J.; Graham, Daniel B.; Gmyrek, Grzegorz B.; Akilesh, Holly M.; Sammut, Benedicte; Bhattacharya, Deepta; Srivatsan, Shuba; Kim, Alfred; Shaw, Andrey S.; Duncavage, Eric; Swat, Wojciech] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Fujikawa, Keiko] Hokkaido Univ, Sch Med, Dept Pathol & Immunol, Sapporo, Hokkaido, Japan. [Yang-Iott, Katherine; Bassing, Craig H.] Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Dept Pathol & Lab Med, Philadelphia, PA USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Xavier, Ramnik J.] Broad Inst, Cambridge, MA USA. RP Swat, W (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, 660 S Euclid Ave, St Louis, MO 63110 USA. EM swat@wustl.edu OI Kim, Alfred/0000-0003-4074-0516 FU NIH [R01AI061077, R01AI073718, DK083756, DK043351, RO1DK058366, R37-AI57966, CA 125195, CA 136470]; Leukemia & Lymphoma Society Scholar Award; Leukemia & Lymphoma Society Special Fellowship Award; Howard Hughes Medical Institute FX This work was supported by NIH grants R01AI061077 and R01AI073718 (to W. Swat), DK083756 and DK043351 (to R.J. Xavier), RO1DK058366 and R37-AI57966 (to A.S. Shaw), CA 125195 and CA 136470 (to C.H. Bassing), the Leukemia & Lymphoma Society Scholar Award (to W. Swat), and Leukemia & Lymphoma Society Special Fellowship Award (to D.B. Graham), and the Howard Hughes Medical Institute (to A.S. Shaw). NR 54 TC 10 Z9 10 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD DEC PY 2013 VL 1 IS 6 BP 426 EP 437 DI 10.1158/2326-6066.CIR-13-0065 PG 12 WC Oncology; Immunology SC Oncology; Immunology GA AM7FP UT WOS:000340030600011 PM 24778134 ER PT J AU Niles, BL Vujanovic, AA Silberbogen, AK Seligowski, AV Potter, CM AF Niles, Barbara L. Vujanovic, Anka A. Silberbogen, Amy K. Seligowski, Antonia V. Potter, Carrie M. TI Changes in Mindfulness Following a Mindfulness Telehealth Intervention SO MINDFULNESS LA English DT Article DE Mindfulness intervention; Measures of mindfulness; Posttraumatic stress disorder; Telehealth; Veteran ID STRESS REDUCTION MBSR; MEDITATION; DEPRESSION; ATTENTION; DISORDER; BENEFITS; THERAPY; PROGRAM; ANXIETY; CANCER AB The goal of this pilot study was to examine changes in self-reported levels of mindfulness in the context of an 8-week mindfulness telehealth intervention for military veterans with combat-related posttraumatic stress disorder (PTSD). Participants were 24 male veterans with PTSD aged 23 to 66 (M=55.2). Participants were randomized to either a mindfulness telehealth intervention or a PTSD psychoeducation telehealth condition. Both interventions consisted of two in-person sessions and six telephone sessions. Measures were collected pre-and posttreatment and at 6-week follow-up and included the Mindful Attention Awareness Scale (MAAS), the White Bear Suppression Inventory (WBSI), and the Five Facets of Mindfulness Questionnaire (FFMQ). Conditions by time interaction effects were found in the expected direction for the MAAS, WBSI, FFMQ Observing, and FFMQ Describing facets, indicating gains in skills for the mindfulness group over the course of the study. Results also suggest that a brief telehealth intervention introducing mindfulness skills may be effective in increasing levels of mindfulness as measured by these instruments. Limitations include a small sample size and lack of intent-to-treat analyses. The present study represents one of the few published studies to use multiple measures of mindfulness to examine changes in mindfulness skills and the first known published study to examine changes in mindfulness following a brief telehealth intervention. C1 [Niles, Barbara L.; Vujanovic, Anka A.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Silberbogen, Amy K.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02130 USA. [Seligowski, Antonia V.; Potter, Carrie M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. RP Niles, BL (reprint author), Boston Univ, Sch Med, VA Boston Healthcare Syst, Natl Ctr PTSD, 150 South Huntington Ave 116B 2, Boston, MA 02130 USA. EM barbara.niles@va.gov NR 35 TC 3 Z9 3 U1 3 U2 17 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1868-8527 EI 1868-8535 J9 MINDFULNESS JI Mindfulness PD DEC PY 2013 VL 4 IS 4 BP 301 EP 310 DI 10.1007/s12671-012-0130-5 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AM1OR UT WOS:000339617300003 ER PT J AU Reber, CAS Boden, MT Mitragotri, N Alvarez, J Gross, JJ Bonn-Miller, MO AF Reber, Cecily A. S. Boden, Matthew Tyler Mitragotri, Neha Alvarez, Jennifer Gross, James J. Bonn-Miller, Marcel O. TI A Prospective Investigation of Mindfulness Skills and Changes in Emotion Regulation Among Military Veterans in Posttraumatic Stress Disorder Treatment SO MINDFULNESS LA English DT Article DE Mindfulness; Acceptance; Emotion regulation; Posttraumatic stress disorder ID COGNITIVE PROCESSING THERAPY; EXPERIENTIAL AVOIDANCE; EMPIRICAL LITERATURE; COMMITMENT THERAPY; SELF-REPORT; ACCEPTANCE; DYSREGULATION; DEPRESSION; ANXIETY; PTSD AB We prospectively investigated associations between mindfulness and changes in the use of expressive suppression and cognitive reappraisal occurring during a residential treatment program for posttraumatic stress disorder (PTSD). The sample consisted of 50 male veterans who were assessed with the Kentucky Inventory of Mindfulness Skills at treatment intake, and the Emotion Regulation Questionnaire (ERQ) and PTSD Checklist-Military Version at treatment intake and discharge. Hierarchical multiple regressions indicated that greater nonjudgmental acceptance at intake predicted greater reductions in expressive suppression (p<.05) and less improvement in cognitive reappraisal (p<.05) between treatment intake and discharge. Additionally, greater ability to observe thoughts, emotions, and sensations at intake was associated with less improvement in cognitive reappraisal between treatment intake and discharge (p<.05). Findings remained significant after statistically adjusting for treatment-related changes in PTSD symptoms. C1 [Reber, Cecily A. S.] VA Palo Alto Hlth Care Syst, PGSP Stanford Psy D Consortium, Menlo Pk, CA 94025 USA. [Boden, Matthew Tyler] VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA 94025 USA. [Bonn-Miller, Marcel O.] VA Palo Alto Hlth Care, Ctr Hlth Care Evaluat, Natl Ctr PTSD, Menlo Pk, CA USA. [Bonn-Miller, Marcel O.] Philadelphia VA Med Ctr, Ctr Excellence Subst Abuse Treatment & Educ, Philadelphia, PA USA. [Mitragotri, Neha; Alvarez, Jennifer] VA Palo Alto Hlth Care Syst, Menlo Pk, CA 94025 USA. [Gross, James J.] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. RP Boden, MT (reprint author), VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, 795 Willow Rd 152 MPD, Menlo Pk, CA 94025 USA. EM matthew.t.boden@gmail.com NR 34 TC 4 Z9 5 U1 6 U2 27 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1868-8527 EI 1868-8535 J9 MINDFULNESS JI Mindfulness PD DEC PY 2013 VL 4 IS 4 BP 311 EP 317 DI 10.1007/s12671-012-0131-4 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AM1OR UT WOS:000339617300004 ER PT J AU La Hoz, RM Baddley, JW AF La Hoz, Ricardo M. Baddley, John W. TI Infectious Complications of Immune Modulatory Agents SO CURRENT INFECTIOUS DISEASE REPORTS LA English DT Article DE Alemtuzumab; Belatacept; Rituximab; Solid organ transplant; Opportunistic infection ID KIDNEY-TRANSPLANT RECIPIENTS; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; CHRONIC LYMPHOCYTIC-LEUKEMIA; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDERS; DOSE MAINTENANCE IMMUNOSUPPRESSION; SOLID-ORGAN TRANSPLANTATION; RITUXIMAB INDUCTION THERAPY; ANTIBODY-MEDIATED REJECTION; B-CELL LYMPHOMA; PHASE-II TRIAL AB Immune modulatory agents used in solid organ transplantation and other disciplines have various mechanisms of action and differences in the duration and intensity of immunosuppression. While newer agents have improved patient outcomes, an important result of these immune modulatory agents is associated infections, caused by organisms such as cytomegalovirus, BK polyomavirus, Epstein-Barr virus and tuberculosis. Herein, we review the infectious complications of several newer immune modulatory drugs-belatacept, alemtuzumab, and rituximab-and focus on their use in solid organ transplantation. New immune modulatory agents can potentially modify the landscape of allograft rejection and noninfectious and infectious complications. Health-care practitioners should remain familiar with these agents and their potential infectious complications to help ensure optimal patient outcomes. C1 [La Hoz, Ricardo M.] Wake Forest Univ, Infect Dis Sect, Dept Med, Winston Salem, NC USA. [Baddley, John W.] Univ Alabama Birmingham, Div Infect Dis, Dept Med, Birmingham, AL 35294 USA. [Baddley, John W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Baddley, JW (reprint author), Univ Alabama Birmingham, Div Infect Dis, Dept Med, 1900 Univ Blvd,Tinsley Harrison Tower 229, Birmingham, AL 35294 USA. EM jbaddley@uab.edu FU BMS FX John Baddley has done consulting for Merck, Astellas and Pfizer and has a pending research grant from BMS. NR 86 TC 2 Z9 2 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3847 EI 1534-3146 J9 CURR INFECT DIS REP JI Curr. Infect. Dis. Rep. PD DEC PY 2013 VL 15 IS 6 BP 465 EP 471 DI 10.1007/s11908-013-0365-x PG 7 WC Infectious Diseases SC Infectious Diseases GA AK2YU UT WOS:000338287300004 PM 24072569 ER PT J AU Chin, JH Mateen, FJ AF Chin, Jerome H. Mateen, Farrah J. TI Central Nervous System Tuberculosis: Challenges and Advances in Diagnosis and Treatment SO CURRENT INFECTIOUS DISEASE REPORTS LA English DT Article DE Tuberculosis; Meningitis; Cerebrospinal; Tuberculoma; HIV; Africa; Xpert ID HIV-INFECTED PATIENTS; EXTRAPULMONARY TUBERCULOSIS; XPERT MTB/RIF; INTRACRANIAL TUBERCULOMAS; MENINGITIS; DEXAMETHASONE; PREDICTION AB Mycobacterium tuberculosis is one of the most prevalent human infections. Although the largest share of the burden of disease is in Africa and Asia, tuberculosis has a global footprint due to travel and migration. Resource constraints in many low- and middle-income countries are hampering efforts to control new infections and to prevent drug resistance. Infection of the central nervous system by Mycobacterium tuberculosis includes meningitis, tuberculoma, and abscess and carries a high morbidity and mortality. High clinical suspicion, combined with cerebrospinal fluid analysis and brain imaging studies, can improve the diagnostic certainty. The recent scale-up of nucleic acid amplification technology may allow earlier diagnosis of tuberculous meningitis in many regions of the world. Treatment of tuberculous infection of the central nervous system is usually empirical and follows conventional regimens for pulmonary tuberculosis. The optimal treatment regimen is still being elucidated and has been the subject of recent clinical trials. C1 [Chin, Jerome H.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Mateen, Farrah J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Chin, JH (reprint author), Univ Calif Berkeley, Sch Publ Hlth, 50 Univ Ave, Berkeley, CA 94720 USA. EM chinj@asapp.org; Farrah.Mateen@gmail.com OI Chin, Jerome/0000-0001-9781-0963 NR 33 TC 6 Z9 7 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3847 EI 1534-3146 J9 CURR INFECT DIS REP JI Curr. Infect. Dis. Rep. PD DEC PY 2013 VL 15 IS 6 BP 631 EP 635 DI 10.1007/s11908-013-0385-6 PG 5 WC Infectious Diseases SC Infectious Diseases GA AK2YU UT WOS:000338287300024 ER PT J AU Zator, ZA Chung, RT AF Zator, Zachary A. Chung, Raymond T. TI After the Cure: Management of HCV After Achievement of SVR SO CURRENT HIV/AIDS REPORTS LA English DT Article DE Hepatitis C, Chronic/drug therapy; Hepatitis C, Chronic/virology; Hepatitis C, Chronic/epidemiology; Humans; Coinfection/drug therapy; Treatment outcome; Elasticity imaging techniques; End stage liver disease/etiology; Liver cirrhosis/complications; Liver cirrhosis/mortality; Liver cirrhosis/physiopathology; Liver cirrhosis/virology; Liver diseases/prevention & control; Liver diseases/virology; Tissue elasticity imaging; Carcinoma, Hepatocellular; HIV infections ID CHRONIC HEPATITIS-C; SUSTAINED VIROLOGICAL RESPONSE; HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED PATIENTS; HEPATOCELLULAR-CARCINOMA; LIVER FIBROSIS; BIOCHEMICAL MARKERS; ESOPHAGEAL-VARICES; UNITED-STATES; GASTROESOPHAGEAL VARICES AB Co-infection with HIV and HCV is associated with accelerated progression of liver disease and increased complications compared with HCV infection alone. Treatment of HCV and achievement of a sustained virologic response (SVR) can improve outcomes in these patients. Even after clearance of the hepatitis C virus, however, patients remain at risk, albeit diminished, for the complications of chronic liver disease. As such, longitudinal monitoring of treated patients remains important for clinicians caring for this population. This article summarizes the benefits and persistent risks after attaining SVR. It reviews the natural history of fibrosis and addresses the monitoring and management of progressive liver disease. C1 [Zator, Zachary A.; Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Warren 1007, Boston, MA 02114 USA. EM zzator@partners.org; rtchung@partners.org NR 52 TC 6 Z9 6 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1548-3568 EI 1548-3576 J9 CURR HIV-AIDS REP JI Curr. Hiv/Aids Rep. PD DEC PY 2013 VL 10 IS 4 BP 428 EP 435 DI 10.1007/s11904-013-0181-9 PG 8 WC Infectious Diseases SC Infectious Diseases GA AJ7TU UT WOS:000337901400014 PM 24218111 ER PT J AU Klann, JG Anand, V Downs, SM AF Klann, Jeffrey G. Anand, Vibha Downs, Stephen M. TI Patient-tailored prioritization for a pediatric care decision support system through machine learning SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID CLINICAL PREVENTIVE SERVICES; CHICA SYSTEM; INFERENCE; ALGORITHM; QUALITY AB Objective Over 8 years, we have developed an innovative computer decision support system that improves appropriate delivery of pediatric screening and care. This system employs a guidelines evaluation engine using data from the electronic health record (EHR) and input from patients and caregivers. Because guideline recommendations typically exceed the scope of one visit, the engine uses a static prioritization scheme to select recommendations. Here we extend an earlier idea to create patient-tailored prioritization. Materials and methods We used Bayesian structure learning to build networks of association among previously collected data from our decision support system. Using area under the receiver-operating characteristic curve (AUC) as a measure of discriminability (a sine qua non for expected value calculations needed for prioritization), we performed a structural analysis of variables with high AUC on a test set. Our source data included 177 variables for 29 402 patients. Results The method produced a network model containing 78 screening questions and anticipatory guidance (107 variables total). Average AUC was 0.65, which is sufficient for prioritization depending on factors such as population prevalence. Structure analysis of seven highly predictive variables reveals both face-validity (related nodes are connected) and non-intuitive relationships. Discussion We demonstrate the ability of a Bayesian structure learning method to 'phenotype the population' seen in our primary care pediatric clinics. The resulting network can be used to produce patient-tailored posterior probabilities that can be used to prioritize content based on the patient's current circumstances. Conclusions This study demonstrates the feasibility of EHR-driven population phenotyping for patient-tailored prioritization of pediatric preventive care services. C1 [Klann, Jeffrey G.] Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. [Klann, Jeffrey G.] Harvard Univ, Sch Med, Boston, MA USA. [Klann, Jeffrey G.] Partners Healthcare Syst Inc, Res Comp, Charlestown, MA 02129 USA. [Anand, Vibha; Downs, Stephen M.] Indiana Univ Sch Med, Childrens Hlth Serv Res, Indianapolis, IN 46202 USA. [Anand, Vibha; Downs, Stephen M.] Regenstrief Inst Hlth Care, Indianapolis, IN 46202 USA. RP Klann, JG (reprint author), Partners Healthcare Syst Inc, Res Comp, Constitut Ctr 1, Charlestown, MA 02129 USA. EM jklann@partners.org FU National Library of Medicine [5T15 LM007117-14, R01LM010031]; Riley Children's Hospital Foundation; Agency for Healthcare Research and Quality [1R01HS018453, R01HS017939] FX This work was supported in part by grant 5T15 LM007117-14 from the National Library of Medicine and a Riley Children's Hospital Foundation grant. Funding for CHICA comes from grants 1R01HS018453 and R01HS017939 from the Agency for Healthcare Research and Quality, and R01LM010031 from the National Library of Medicine. NR 43 TC 4 Z9 4 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1067-5027 EI 1527-974X J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD DEC PY 2013 VL 20 IS E2 BP E267 EP E274 DI 10.1136/amiajnl-2013-001865 PG 8 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA AI0EA UT WOS:000336517800012 PM 23886921 ER PT J AU Sosenko, JM Skyler, JS Beam, CA Krischer, JP Greenbaum, CJ Mahon, J Rafkin, LE Matheson, D Herold, KC Palmer, JP AF Sosenko, Jay M. Skyler, Jay S. Beam, Craig A. Krischer, Jeffrey P. Greenbaum, Carla J. Mahon, Jeffrey Rafkin, Lisa E. Matheson, Della Herold, Kevan C. Palmer, Jerry P. CA Type 1 Diabet TrialNet Grp Diabet Prevention Trial-Type 1 Stu TI Acceleration of the Loss of the First-Phase Insulin Response During the Progression to Type 1 Diabetes in Diabetes Prevention Trial-Type 1 Participants SO DIABETES LA English DT Article ID RELATIVES; MELLITUS; SECRETION; MARKERS; ONSET AB We studied the change in the first-phase insulin response (FPIR) during the progression to type 1 diabetes (T1D). Seventy-four oral insulin trial progressors to T1D from the Diabetes Prevention Trial-Type 1 with at least one FPIR measurement after baseline and before diagnosis were studied. The FPIR was examined longitudinally in 26 progressors who had FPIR measurements during each of the 3 years before diagnosis. The association between the change from the baseline FPIR to the last FPIR and time to diagnosis was studied in the remainder (n = 48). The 74 progressors had lower baseline FPIR values than nonprogressors (n = 270), with adjustments made for age and BMI. In the longitudinal analysis of the 26 progressors, there was a greater decline in the FPIR from 1.5 to 0.5 years before diagnosis than from 2.5 to 1.5 years before diagnosis. This accelerated decline was also evident in a regression analysis of the 48 remaining progressors in whom the rate of decline became more marked with the approaching diagnosis. The patterns of decline were similar between the longitudinal and regression analyses. There is an acceleration of decline in the FPIR during the progression to T1D, which becomes especially marked between 1.5 and 0.5 years before diagnosis. C1 [Sosenko, Jay M.; Skyler, Jay S.; Rafkin, Lisa E.; Matheson, Della] Univ Miami, Div Endocrinol, Miami, FL 33136 USA. [Beam, Craig A.; Krischer, Jeffrey P.] Univ S Florida, Div Informat & Biostat, Tampa, FL USA. [Greenbaum, Carla J.] Virginia Mason, Benaroya Res Inst, Seattle, WA USA. [Mahon, Jeffrey] Univ Western Ontario, Dept Epidemiol & Biostat, London, ON, Canada. [Herold, Kevan C.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA. [Palmer, Jerry P.] Univ Washington, VA Puget Sound Hlth Care Syst, Div Endocrinol Metab & Nutr, Seattle, WA 98195 USA. RP Sosenko, JM (reprint author), Univ Miami, Div Endocrinol, Miami, FL 33136 USA. EM jsosenko@med.miami.edu RI Skyler, Jay/F-4211-2016; OI Gallagher, Mary/0000-0002-5844-2309 FU National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health through the National Institute of Allergy and Infectious Diseases; National Institutes of Health through the Eunice Kennedy Shriver National Institute of Child Health and Human Development [U01-DK-061010, U01-DK-061016, U01-DK-061034, U01-DK-061036, U01-DK-061040, U01-DK-061041, U01-DK-061042, U01-DK-061055, U01-DK-061058, U01-DK-084565, U01-DK-085453, U01-DK-085461, U01-DK-085463, U01-DK-085466, U01-DK-085499, U01-DK-085505, U01-DK-085509, HHSN267200800019C]; National Center for Research Resources through Clinical Translational Science Awards [UL1-RR-024131, UL1-RR-024139, UL1-RR-024153, UL1-RR-024975, UL1-RR-024982, UL1-RR-025744, UL1-RR-025761, UL1-RR-025780, UL1-RR-029890, UL1-RR-031986, P30-DK-017047]; General Clinical Research Center [M01-RR-00400]; JDRF; American Diabetes Association FX The sponsor of the trial was the Type 1 Diabetes TrialNet Study Group, which is a clinical trials network funded by the National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development through cooperative agreements U01-DK-061010, U01-DK-061016, U01-DK-061034, U01-DK-061036, U01-DK-061040, U01-DK-061041, U01-DK-061042, U01-DK-061055, U01-DK-061058, U01-DK-084565, U01-DK-085453, U01-DK-085461, U01-DK-085463, U01-DK-085466, U01-DK-085499, U01-DK-085505, and U01-DK-085509 and contract HHSN267200800019C; the National Center for Research Resources through Clinical Translational Science Awards UL1-RR-024131, UL1-RR-024139, UL1-RR-024153, UL1-RR-024975, UL1-RR-024982, UL1-RR-025744, UL1-RR-025761, UL1-RR-025780, UL1-RR-029890, UL1-RR-031986, and P30-DK-017047 and General Clinical Research Center Award M01-RR-00400; JDRF; and the American Diabetes Association. NR 15 TC 18 Z9 18 U1 0 U2 16 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD DEC PY 2013 VL 62 IS 12 BP 4179 EP 4183 DI 10.2337/db13-0656 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AE1OJ UT WOS:000333738500034 PM 23863814 ER PT J AU Zhang, W Liu, JR Tian, L Liu, QL Fu, YC Garvey, WT AF Zhang, Wei Liu, Jiarong Tian, Ling Liu, Qinglan Fu, Yuchang Garvey, W. Timothy TI TRIB3 Mediates Glucose-Induced Insulin Resistance via a Mechanism That Requires the Hexosamine Biosynthetic Pathway SO DIABETES LA English DT Article ID LINKED N-ACETYLGLUCOSAMINE; HUMAN SKELETAL-MUSCLE; II DIABETES-MELLITUS; O-GLCNAC; GLUTAMINE-FRUCTOSE-6-PHOSPHATE AMIDOTRANSFERASE; TRIBBLES HOMOLOG; TRANSPORT SYSTEM; NUCLEOCYTOPLASMIC PROTEINS; INDUCED DESENSITIZATION; BIOCHEMICAL PATHWAYS AB In the current study, we investigated the role of tribbles homolog 3 (TRIB3) in glucose-induced insulin resistance and whether the induction of TRIB3 by glucose is dependent on the nutrient-sensing hexosamine biosynthetic pathway (HBP) known to mediate glucose toxicity in diabetes. In diabetic rats, TRIB3 expression in skeletal muscle was increased after 10 days of hyperglycemia, and glycemia and muscle TRIB3 were both restored toward normal by insulin therapy. In L6 myocytes, the induction of TRIB3 by high glucose or glucosamine was reversible upon removal of these substrates. To assess the role of HBP in the induction of TRIB3, we demonstrated that the ability of high glucose to augment TRIB3 expression was prevented by azaserine, an inhibitor of glutamine: fructose-6-phosphate amidotransferase (GFAT), which is the rate-limiting enzyme in the HBP pathway. TRIB3 expression was also substantially stimulated by glucosamine, which bypasses GFAT, accompanied by a decrease in the insulin-stimulated glucose transport rate, and neither response was affected by azaserine. Further, knockdown of TRIB3 inhibited, and TRIB3 overexpression enhanced, the ability of both high glucose and glucosamine to induce insulin resistance. These data provide the mechanistic link between the HBP flux and insulin resistance and point to TRIB3 as a novel target for treatment of glucose-induced insulin resistance. C1 [Zhang, Wei; Tian, Ling; Fu, Yuchang; Garvey, W. Timothy] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. [Liu, Jiarong; Liu, Qinglan] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Garvey, W. Timothy] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Zhang, W (reprint author), Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. EM siweizh@uab.edu FU National Institutes of Health [DK-038765, DK-083562]; Merit Review program of the Department of Veterans Affairs; Amylin; Merck; Weight Watchers FX This work was supported by grants from the National Institutes of Health (DK-038765 and DK-083562) and by the Merit Review program of the Department of Veterans Affairs. We also acknowledge support from core facilities of the University of Alabama (UAB) Diabetes Research Center (P60 DK-079626).; W.T.G. has served on advisory boards for Novo Nordisk, Eisai, Daiichi Sankyo, Liposcience, Vivus, Janssen, Boehringer Ingelheim, and Bristol-Myers Squibb/AstraZeneca; speaker's list for Merck, Eisai, and Amylin; sponsored research funded by Amylin, Merck, and Weight Watchers. No other potential conflicts of interest relevant to this article were reported. NR 50 TC 10 Z9 10 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD DEC PY 2013 VL 62 IS 12 BP 4192 EP 4200 DI 10.2337/db13-0312 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AE1OJ UT WOS:000333738500036 PM 23990361 ER PT J AU Muscogiuri, G Salmon, AB Aguayo-Mazzucato, C Li, MY Balas, B Guardado-Mendoza, R Giaccari, A Reddick, RL Reyna, SM Weir, G DeFronzo, RA Van Remmen, H Musi, N AF Muscogiuri, Giovanna Salmon, Adam B. Aguayo-Mazzucato, Cristina Li, Mengyao Balas, Bogdan Guardado-Mendoza, Rodolfo Giaccari, Andrea Reddick, Robert L. Reyna, Sara M. Weir, Gordon DeFronzo, Ralph A. Van Remmen, Holly Musi, Nicolas TI Genetic Disruption of SOD1 Gene Causes Glucose Intolerance and Impairs beta- Cell Function SO DIABETES LA English DT Article ID OXIDATIVE STRESS; INSULIN-RESISTANCE; GLUTATHIONE-PEROXIDASE; LIPID-PEROXIDATION; ATHEROSCLEROSIS; EXPRESSION; TOXICITY; PATHWAY; MODEL; LEADS AB Oxidative stress has been associated with insulin resistance and type 2 diabetes. However, it is not clear whether oxidative damage is a cause or a consequence of the metabolic abnormalities present in diabetic subjects. The goal of this study was to determine whether inducing oxidative damage through genetic ablation of superoxide dismutase 1 (SOD1) leads to abnormalities in glucose homeostasis. We studied SOD1-null mice and wild-type (WT) littermates. Glucose tolerance was evaluated with intraperitoneal glucose tolerance tests. Peripheral and hepatic insulin sensitivity was quantitated with the euglycemic-hyperinsulinemic clamp. -Cell function was determined with the hyperglycemic clamp and morphometric analysis of pancreatic islets. Genetic ablation of SOD1 caused glucose intolerance, which was associated with reduced in vivo -cell insulin secretion and decreased -cell volume. Peripheral and hepatic insulin sensitivity were not significantly altered in SOD1-null mice. High-fat diet caused glucose intolerance in WT mice but did not further worsen the glucose intolerance observed in standard chow-fed SOD1-null mice. Our findings suggest that oxidative stress per se does not play a major role in the pathogenesis of insulin resistance and demonstrate that oxidative stress caused by SOD1 ablation leads to glucose intolerance secondary to -cell dysfunction. C1 [Muscogiuri, Giovanna; Li, Mengyao; Balas, Bogdan; Guardado-Mendoza, Rodolfo; Reyna, Sara M.; DeFronzo, Ralph A.; Musi, Nicolas] Univ Texas Hlth Sci Ctr San Antonio, Diabet Div, San Antonio, TX 78229 USA. [Salmon, Adam B.; Van Remmen, Holly; Musi, Nicolas] Barshop Inst Longev & Aging Studies, San Antonio, TX USA. [Salmon, Adam B.; Van Remmen, Holly; Musi, Nicolas] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. [Aguayo-Mazzucato, Cristina; Weir, Gordon] Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02215 USA. [Giaccari, Andrea] Univ Cattolica Sacro Cuore, Div Endocrinol & Metab Dis, Policlin A Gemelli, Rome, Italy. [Giaccari, Andrea] Fdn Don C Gnocchi, Milan, Italy. [Reddick, Robert L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. RP Musi, N (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Diabet Div, San Antonio, TX 78229 USA. EM musi@uthscsa.edu FU Fondazione Don Gnocchi; Italian Ministry of Education, University and Research [PRIN 2010JS3PMZ_011]; National Institutes of Health [R01DK66056, DK93909, P30DK36836]; JDRF; Diabetes Research and Wellness Foundation; National Institute on Aging [P01AG020591, K23AG030979]; American Federation for Aging Research; National Institute of Diabetes and Digestive and Kidney Diseases [RO1DK089229, R01DK089229]; American Diabetes Association; Universita Cattolica del Sacro Cuore (Fondi Ateneo Linea D.3.2 Sindrome Metabolica) FX A.G. was supported by grants from Fondazione Don Gnocchi, Universita Cattolica del Sacro Cuore (Fondi Ateneo Linea D.3.2 Sindrome Metabolica), and the Italian Ministry of Education, University and Research (PRIN 2010JS3PMZ_011). G.W. was supported by the National Institutes of Health (R01DK66056 and DK93909 and P30DK36836 [Joslin Diabetes Research Center]), JDRF, and Diabetes Research and Wellness Foundation. H.V.R. was supported by grant P01AG020591 from the National Institute on Aging. N.M. was supported by a Paul B. Beeson Award from the National Institute on Aging (K23AG030979) and the American Federation for Aging Research and grants from the National Institute of Diabetes and Digestive and Kidney Diseases (RO1DK089229 and R01DK089229) and the American Diabetes Association. NR 35 TC 11 Z9 11 U1 1 U2 39 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD DEC PY 2013 VL 62 IS 12 BP 4201 EP 4207 DI 10.2337/db13-0314 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AE1OJ UT WOS:000333738500037 PM 24009256 ER PT J AU Bray, JR AF Bray, Janice R. TI Genitourinary Trauma: A Battle Cry for Integrated Collaborative Veteran-Centric Care SO JOURNAL OF MENS HEALTH LA English DT Editorial Material ID SEXUAL DYSFUNCTION; COMBAT VETERANS; AFGHANISTAN; IRAQ C1 US Dept Vet Affairs, Temple Mental Hlth & Behav Med, Cent Texas Vet Hlth Care Syst, Temple, TX 76504 USA. RP Bray, JR (reprint author), US Dept Vet Affairs, Temple Mental Hlth & Behav Med, Cent Texas Vet Hlth Care Syst, 1901 Vet Mem Dr, Temple, TX 76504 USA. EM janice.bray@va.gov NR 20 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1875-6867 EI 1875-6859 J9 J MENS HEALTH JI J. Mens Health PD DEC PY 2013 VL 10 IS 4 BP 121 EP 123 DI 10.1089/jomh.2013.0028 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AD2AA UT WOS:000333033600002 ER PT J AU Bruner, B Nehra, A Rangel, L Bailey, C Bergstralh, E Blute, M Karnes, RJ AF Bruner, Bryan Nehra, Ajay Rangel, Laureano Bailey, Chris Bergstralh, Eric Blute, Michael Karnes, R. Jeffrey TI Association of Preoperative Testosterone Levels with Biochemical Failure in Men Undergoing Radical Prostatectomy SO JOURNAL OF MENS HEALTH LA English DT Article DE hypogonadism; prostate cancer; sexual medicine; urology ID LOW SERUM TESTOSTERONE; PATHOLOGICAL STAGE; CANCER; PREDICTOR AB Background: Low testosterone levels in men treated with radical prostatectomy (RP) for prostate cancer have been associated with worse pathological stage and outcomes. Long-term data correlating preoperative testosterone levels and RP outcomes are presented. Methods: A total of 177 patients were identified who had preoperative testosterone levels and were treated with RP with long-term follow-up. Associations of testosterone levels with tumor stage, Gleason score, and time to biochemical failure (BCF) were assessed using Pearson's chi-square test, Mantel-Haenszel test, Spearman rank correlation, and life-table methods (Kaplan-Meier curves, log-rank test, Cox proportional hazards model) as appropriate. Testosterone was analyzed both as a continuous factor and as low (< 300 ng/dl) versus normal testosterone levels. Results: The median testosterone level was 423 ng/dl, median age was 65 years, and median follow-up was approximately 15 years. A significant association between testosterone values below 300 ng/dl and positive surgical margin (p = 0.0389) as well as seminal vesicle invasion (p = 0.0182) was found. While patients with a testosterone level < 300 ng/dl also showed a higher percentage of BCF over time (45% vs. 29% at 15 years), the difference was not statistically significant (p = 0.076, log-rank test). When adjusted for known predictors of BCF (Gleason score, pre-RP prostate-specific antigen, seminal vesicle involvement, and positive surgical margin), the effect of testosterone as a continuous predictor was not statistically significant (p = 0.57). Conclusion: The longest follow-up to date (15 years) correlating preoperative testosterone levels and RP outcomes is presented. With this study, low testosterone levels were significantly associated with a positive surgical margin and seminal vesicle invasion, and slightly higher (p = 076) BCF rates. C1 [Bruner, Bryan] Baylor Grapevine, Urol Clin North Texas, Grapevine, TX USA. [Nehra, Ajay] Rush Univ, Med Ctr, Dept Urol, Chicago, IL 60612 USA. [Rangel, Laureano; Bergstralh, Eric] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Bailey, Chris; Karnes, R. Jeffrey] Mayo Clin, Dept Urol, Rochester, MN 55905 USA. [Blute, Michael] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Karnes, RJ (reprint author), Mayo Clin, Dept Urol, 200 1st St SW, Rochester, MN 55905 USA. EM karnes.r@mayo.edu NR 13 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1875-6867 EI 1875-6859 J9 J MENS HEALTH JI J. Mens Health PD DEC PY 2013 VL 10 IS 4 BP 129 EP 133 DI 10.1089/jomh.2013.0016 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AD2AA UT WOS:000333033600004 ER PT J AU Steensma, DP Gattermann, N AF Steensma, David P. Gattermann, Norbert TI When is iron overload deleterious, and when and how should iron chelation therapy be administered in myelodysplastic syndromes? SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY LA English DT Article DE iron; red blood cell transfusion [complications]; haemosiderosis; myelodysplastic syndromes; chelation therapy; deferasirox; deferoxamine; deferiprone ID STEM-CELL TRANSPLANTATION; TRANSFUSION-DEPENDENT PATIENTS; OXIDATIVE DNA-DAMAGE; BETA-THALASSEMIA MAJOR; LABILE PLASMA IRON; LONG-TERM THERAPY; SERUM FERRITIN; BONE-MARROW; DEFERASIROX TREATMENT; CARDIAC IRON AB Iron overload in MDS starts even before patients become red-blood cell transfusion dependent, because disease-associated ineffective erythropoiesis suppresses hepcidin production in the liver and thus causes unrestrained iron absorption in the duodenum. However, the main cause of iron overload is regular transfusion therapy, which in MDS is associated with a risk of unclear magnitude for iron-related complications. Iron deposition in tissues can now be detected with non-invasive techniques such as T2* MRI. Iron toxicity in MDS may not only depend on the degree of tissue iron accumulation but also on the extent of chronic exposure to non-transferrin-bound iron (NTBI), including labile plasma iron (LPI) and intracellular labile iron pools, which increase the level of oxidative stress. Iron chelation therapy (ICT) can rapidly lower NTBI and LPI and more slowly mobilizes tissue iron stores. Further studies, including the ongoing TELESTO controlled trial, will more clearly define the role of ICT in MDS, including any effect on specific morbidities or mortality in the MDS setting. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Steensma, David P.] Dana Farber Canc Inst, Boston, MA USA. [Steensma, David P.] Harvard Univ, Sch Med, Boston, MA USA. [Gattermann, Norbert] Univ Dusseldorf, Klin Hamatol Onkol & Klin Immunol, D-40225 Dusseldorf, Germany. RP Gattermann, N (reprint author), Univ Dusseldorf, Klin Hamatol Onkol & Klin Immunol, Moorenstr 5, D-40225 Dusseldorf, Germany. EM gattermann@med.uni-duesseldorf.de OI Steensma, David/0000-0001-5130-9284 NR 102 TC 12 Z9 12 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1521-6926 EI 1532-1924 J9 BEST PRACT RES CL HA JI Best Pract. Res. Clin. Haematol. PD DEC PY 2013 VL 26 IS 4 BP 431 EP 444 DI 10.1016/j.beha.2013.09.009 PG 14 WC Hematology SC Hematology GA AC0NB UT WOS:000332190900013 PM 24507819 ER PT J AU Allison, TA AF Allison, Theresa A. TI The Culture of AIDS in Africa: Hope and Healing Through Music and the Arts SO ETHNOMUSICOLOGY LA English DT Book Review ID TRANSMISSION C1 [Allison, Theresa A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Allison, Theresa A.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Allison, TA (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 8 TC 0 Z9 0 U1 0 U2 1 PU SOC ETHNOMUSICOLOGY INC PI BLOOMINGTON PA MORRISON HALL, ROOM 005 INDIANA UNIVERSITY, BLOOMINGTON, IN 47405 USA SN 0014-1836 EI 2156-7417 J9 ETHNOMUSICOLOGY JI Ethnomusicology PD WIN PY 2013 VL 57 IS 1 BP 138 EP 142 PG 5 WC Music SC Music GA AC0LT UT WOS:000332187500014 ER PT J AU Bauer, KA AF Bauer, Kenneth A. TI Pros and cons of new oral anticoagulants SO HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM LA English DT Article ID NONVALVULAR ATRIAL-FIBRILLATION; ACUTE VENOUS THROMBOEMBOLISM; TOTAL KNEE ARTHROPLASTY; FACTOR XA; PREVENT THROMBOEMBOLISM; HIP-ARTHROPLASTY; 1ST-LINE AGENTS; RISK-FACTORS; RIVAROXABAN; DABIGATRAN AB The availability of new ora anticoagulants (NOACs) targeting either thrombin (dabigatran etexilate) or factor Xa (rivaroxaban and apixaban) for the prevention and treatment of thrombosis has been highly anticipated NOACs have major pharmacologic advantages over vitamin K antagonists (eg, warfarin), including rapid onset/offset of action, few drug interactions, and predictable pharmacokinetics, eliminating the requirement for regular coagulation monitoring. Regulatory agencies have approved several NOACs for specific indications based on the results of clinical trials demonstrating efficacy and safety that are at least as good, if not better, than warfarin (for stroke prevention in atrial fibrillation and treatment and secondary prevention of venous thromboembolism) or low-molecular-weight heparin, which is injectable (for initial treatment of venous thromboembolism and thromboprophylaxis in patients undergoing hip or knee arthroplasty). However, the adoption of this new therapeutic class into clinical practice has been slower than expected due to several factors including concerns regarding medication adherence without laboratory monitoring, uncertainty about dosing in some patient populations (eg, renal dysfunction, marked extremes of body weight), and higher drug costs compared with warfarin. Other issues are the current absence of specific antidotes for NOACs and assays to measure drug levels at most centers. The indications for NOACs on the market will expand and at least one additional agent (edoxaban) will likely gain approval within the next 2 years. As practitioners gain familiarity with the drugs and healthcare systems adapt to their use, NOAC use will increase substantially over time, Warfarin, however, will continue to be an appropriate anticoagulant choice for many patients. C1 [Bauer, Kenneth A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Bauer, Kenneth A.] Harvard Univ, Sch Med, Dept Med, VA Boston Healthcare Syst, Boston, MA USA. RP Bauer, KA (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215 USA. EM kbauer@bidmc.harvard.edu NR 46 TC 45 Z9 46 U1 1 U2 13 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 1520-4391 EI 1520-4383 J9 HEMATOL-AM SOC HEMAT JI Hematol.-Am. Soc. Hematol. Educ. Program PD DEC PY 2013 BP 464 EP 470 PG 7 WC Education, Scientific Disciplines; Hematology SC Education & Educational Research; Hematology GA AB6LP UT WOS:000331900300067 ER PT J AU Viswanathan, AN Damato, AL Nguyen, PL AF Viswanathan, Akila N. Damato, Antonio L. Nguyen, Paul L. TI Novel Use of a Hydrogel Spacer Permits Reirradiation in Otherwise Incurable Recurrent Gynecologic Cancers SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID RADIATION-THERAPY; ONCOLOGY-GROUP; BRACHYTHERAPY; TRIAL; CARCINOMA C1 [Damato, Antonio L.; Nguyen, Paul L.] Brigham & Womens Hosp, Dana Farber Canc Inst, Harvard Med Sch, Boston, MA USA. RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Harvard Med Sch, Boston, MA USA. NR 11 TC 7 Z9 7 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 1 PY 2013 VL 31 IS 34 BP E446 EP E447 DI 10.1200/JCO.2012.47.9931 PG 2 WC Oncology SC Oncology GA 277KD UT WOS:000328816600028 PM 24145342 ER PT J AU Joseph, A Spector, L Wickham, K Janis, G Winickoff, J Lindgren, B Murphy, S AF Joseph, Anne Spector, Logan Wickham, Katherine Janis, Gregory Winickoff, Jonathan Lindgren, Bruce Murphy, Sharon TI Biomarker Evidence of Tobacco Smoke Exposure in Children Participating in Lead Screening SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID UNITED-STATES; US CHILDREN; SECONDHAND SMOKE; PASSIVE SMOKING; ADOLESCENTS; DETERMINANTS; COTININE; ADULTS; RISK AB Objectives. We assessed tobacco smoke exposure (TSE), defined according to detection of cotinine, in dried blood spots collected from children for lead screening. Methods. Dried blood spots collected from a national sample of 1541 Black and White children and submitted to a commercial laboratory for lead analysis were analyzed for cotinine. We used an anonymous administrative data set including information on children's characteristics to conduct univariate and multivariate analyses. Results. Cotinine was detected in 61% of dried blood spots; 17% of samples had cotinine levels above 3 nanograms per gram. Median cotinine levels were significantly higher among Black than White children (0.66 ng/g vs 0.30 ng/g) and among Medicaid recipients (0.94 ng/g vs < 0.3 ng/g). In multivariate analyses, significant increases in cotinine levels were associated with Black (vs White) race, older age, Medicaid coverage, higher state smoking rate, and higher average winter temperature. Detectable cotinine levels were significantly associated with higher lead levels. Conclusions. TSE is highly prevalent among children undergoing lead screening, and exposure levels are greater among Black children and children on Medicaid. TSE may contribute to lead exposure. Concurrent lead screening and biological screening for TSE may be a feasible approach to increasing childhood TSE detection. C1 [Joseph, Anne] Univ Minnesota, Masonic Canc Ctr, Dept Med, Minneapolis, MN 55414 USA. [Spector, Logan] Univ Minnesota, Masonic Canc Ctr, Dept Pediat, Minneapolis, MN 55414 USA. [Wickham, Katherine] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55414 USA. [Janis, Gregory] MEDTOX Labs, St Paul, MN USA. [Winickoff, Jonathan] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Res & Policy, Boston, MA 02114 USA. [Winickoff, Jonathan] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Winickoff, Jonathan] Harvard Univ, Sch Med, Boston, MA USA. [Lindgren, Bruce] Univ Minnesota, Biostat & Bioinformat Core, Minneapolis, MN 55414 USA. [Murphy, Sharon] Univ Minnesota, Masonic Canc Ctr, Dept Biochem Mol Biol & BioPhys, Minneapolis, MN 55414 USA. RP Joseph, A (reprint author), Univ Minnesota, 717 Delaware SE,Suite 166, Minneapolis, MN 55414 USA. EM amjoseph@umn.edu OI Spector, Logan/0000-0003-2516-0222 FU National Heart, Lung, and Blood Institute (NHLBI) [1RC2HL10140, P30 CA-77598] FX This work was supported by the National Heart, Lung, and Blood Institute (NHLBI; grant 1RC2HL10140). Liquid chromatography tandem mass spectrometry analyses were carried out in the analytical biochemistry shared resource facility of the Masonic Cancer Center and supported in part by NHLBI (grant P30 CA-77598). NR 29 TC 2 Z9 2 U1 0 U2 4 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2013 VL 103 IS 12 BP E54 EP E59 DI 10.2105/AJPH.2013.301315 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AA4CV UT WOS:000331043200013 PM 24134342 ER PT J AU Mikesell, L Bromley, E Khodyakov, D AF Mikesell, Lisa Bromley, Elizabeth Khodyakov, Dmitry TI Ethical Community-Engaged Research: A Literature Review SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Review ID PARTICIPATORY ACTION RESEARCH; HEALTH RESEARCH; INTERVENTION RESEARCH; CONDUCTING RESEARCH; GENETIC RESEARCH; NORTH-CAROLINA; PUBLIC-HEALTH; CHALLENGES; BOARD; PARTNERSHIP AB Health research has relied on ethical principles, such as those of the Belmont Report, to protect the rights and well-being of research participants. Community-based participatory research (CBPR), however, must also consider the rights and wellbeing of communities. This requires additional ethical considerations that have been extensively discussed but not synthesized in the CBPR literature. We conducted a comprehensive thematic literature review and summarized empirically grounded discussions of ethics in CBPR, with a focus on the value of the Belmont principles in CBPR, additional essential components of ethical CBPR, the ethical challenges CBPR practitioners face, and strategies to ensure that CBPR meets ethical standards. Our study provides a foundation for developing a working definition and a conceptual model of ethical CBPR. C1 [Mikesell, Lisa] Rutgers State Univ, Sch Commun & Informat, Dept Commun, New Brunswick, NJ 08901 USA. [Bromley, Elizabeth] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Semel Inst Ctr Hlth Serv & Soc, Los Angeles, CA 90024 USA. [Bromley, Elizabeth] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. [Khodyakov, Dmitry] RAND Corp, Santa Monica, CA USA. RP Mikesell, L (reprint author), Rutgers State Univ, Sch Commun & Informat, Dept Commun, 4 Huntington St, New Brunswick, NJ 08901 USA. EM lisa.mikesell@rutgers.edu FU Office of Research Integrity; National Institute of Environmental Health Sciences [R21ES022093] FX This research was supported by the Office of Research Integrity and the National Institute of Environmental Health Sciences (grant R21ES022093). NR 71 TC 25 Z9 25 U1 4 U2 25 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2013 VL 103 IS 12 BP E7 EP E14 DI 10.2105/AJPH.2013.301605 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AA4CV UT WOS:000331043200008 PM 24134352 ER PT J AU Bharel, M Lin, WC Zhang, JY O'Connell, E Taube, R Clark, RE AF Bharel, Monica Lin, Wen-Chieh Zhang, Jianying O'Connell, Elizabeth Taube, Robert Clark, Robin E. TI Health Care Utilization Patterns of Homeless Individuals in Boston: Preparing for Medicaid Expansion Under the Affordable Care Act SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID CASE-MANAGEMENT PROGRAM; HEPATITIS-C VIRUS; SERVICE USE; ADULTS; DISORDERS; COSTS; PREVALENCE; EMERGENCY; QUALITY; COHORT AB Objectives. We studied 6494 Boston Health Care for the Homeless Program (BHCHP) patients to understand the disease burden and health care utilization patterns for a group of insured homeless individuals. Methods. We studied merged BHCHP data and MassHealth eligibility, claims, and encounter data from 2010. MassHealth claims and encounter data provided a comprehensive history of health care utilization and expenditures, as well as associated diagnoses, in both general medical and behavioral health services sectors and across a broad range of health care settings. Results. The burden of disease was high, with the majority of patients experiencing mental illness, substance use disorders, and a number of medical diseases. Hospitalization and emergency room use were frequent and total expenditures were 3.8 times the rate of an average Medicaid recipient. Conclusions. The Affordable Care Act provides a framework for reforming the health care system to improve the coordination of care and outcomes for vulnerable populations. However, improved health care coverage alone may not be enough. Health care must be integrated with other resources to address the complex challenges presented by inadequate housing, hunger, and unsafe environments. C1 [Bharel, Monica; Taube, Robert] Boston Hlth Care Homeless Program, Boston, MA 02118 USA. [Bharel, Monica] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Bharel, Monica] Boston Med Ctr, Boston, MA USA. [Lin, Wen-Chieh; Zhang, Jianying; O'Connell, Elizabeth; Clark, Robin E.] Univ Massachusetts, Sch Med, Ctr Hlth Policy & Res, Boston, MA 02125 USA. [Lin, Wen-Chieh; Clark, Robin E.] Univ Massachusetts, Sch Med, Dept Family Med & Community Hlth, Boston, MA 02125 USA. RP Bharel, M (reprint author), Boston Hlth Care Homeless Program, 780 Albany St, Boston, MA 02118 USA. EM mbharel@bhchp.org NR 30 TC 20 Z9 20 U1 4 U2 15 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2013 VL 103 SU 2 BP S311 EP S317 DI 10.2105/AJPH.2013.301421 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AA4NP UT WOS:000331073100031 PM 24148046 ER PT J AU Casey, R Clark, C Smits, P Peters, R AF Casey, Roger Clark, Colleen Smits, Paul Peters, Roger TI Application of Implementation Science for Homeless Interventions SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID INTERACTIVE SYSTEMS FRAMEWORK C1 [Casey, Roger] US Dept Vet Affairs, Natl Ctr Homelessness Vet, Tampa, FL USA. [Clark, Colleen; Peters, Roger] Univ S Florida, Dept Mental Hlth, Law & Policy Inst, Tampa, FL USA. [Smits, Paul] Univ S Florida, Natl Ctr Homelessness Vet, Tampa, FL USA. RP Casey, R (reprint author), Natl Ctr Homelessness Vet, 8900 Grand Oak Circle 116H, Tampa, FL 33617 USA. EM roger.casey@va.gov NR 7 TC 1 Z9 1 U1 1 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2013 VL 103 SU 2 BP S183 EP S185 DI 10.2105/AJPH.2013.301729 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AA4NP UT WOS:000331073100007 PM 24148045 ER PT J AU Culhane, DP Kane, V Johnston, M AF Culhane, Dennis P. Kane, Vincent Johnston, Mark TI Homelessness Research: Shaping Policy and Practice, Now and Into the Future SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID MENTAL-ILLNESS C1 [Culhane, Dennis P.; Kane, Vincent] US Dept Vet Affairs, Natl Ctr Homelessness Vet, Washington, DC USA. [Culhane, Dennis P.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. [Johnston, Mark] US Dept Housing & Urban Dev, Off Community Planning & Dev, Washington, DC USA. RP Kane, V (reprint author), Vet Affiars Dept Homelessness, VA Ctr Homelessness Vet, 4100 Chester Ave, Philadelphia, PA 19106 USA. EM Vincent.kane@va.gov NR 9 TC 0 Z9 0 U1 3 U2 10 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2013 VL 103 SU 2 BP S181 EP S183 DI 10.2105/AJPH.2013.301728 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AA4NP UT WOS:000331073100006 PM 24148044 ER PT J AU Doran, KM Vashi, AA Platis, S Curry, LA Rowe, M Gang, M Vaca, FE AF Doran, Kelly M. Vashi, Anita A. Platis, Stephanie Curry, Leslie A. Rowe, Michael Gang, Maureen Vaca, Federico E. TI Navigating the Boundaries of Emergency Department Care: Addressing the Medical and Social Needs of Patients Who Are Homeless SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID HEALTH-SERVICES RESEARCH; SAFETY-NET EMERGENCY; NEW-YORK-CITY; PEOPLE; ADULTS; URBAN; INSTABILITY; POPULATION; PATTERNS; ALCOHOL AB Objectives. We sought to understand interpersonal and systems-level factors relevant to delivering health care to emergency department (ED) patients who are homeless. Methods. We conducted semistructured interviews with emergency medicine residents from 2 residency programs, 1 in New York City and 1 in a medium-sized northeastern city, from February to September 2012. A team of researchers reviewed transcripts independently and coded text segments using a grounded theory approach. They reconciled differences in code interpretations and generated themes inductively. Data collection and analysis occurred iteratively, and interviews continued until theoretical saturation was achieved. Results. From 23 interviews, 3 key themes emerged: (1) use of pattern recognition in identifying and treating patients who are homeless, (2) variations from standard ED care for patients who are homeless, and (3) tensions in navigating the boundaries of ED social care. Conclusions. Our study revealed practical and philosophical tensions in providing social care to patients in the ED who are homeless. Screening for homelessness in the ED and admission practices for patients who are homeless are important areas for future research and intervention with implications for health care costs and patient outcomes. C1 [Doran, Kelly M.; Vashi, Anita A.] Yale Univ, Sch Med, US Dept Vet Affairs, Robert Wood Johnson Fdn,Clin Scholars Program, New Haven, CT USA. [Doran, Kelly M.; Vashi, Anita A.; Vaca, Federico E.] Yale Univ, Sch Med, Dept Emergency Med, New Haven, CT USA. [Platis, Stephanie; Curry, Leslie A.] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Curry, Leslie A.] Yale Univ, Sch Med, Robert Wood Johnson Fdn, Clin Scholars Program, New Haven, CT USA. [Rowe, Michael] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Doran, Kelly M.; Gang, Maureen] NYU, Bellevue Hosp Ctr, Sch Med, Dept Emergency Med, New York, NY 10016 USA. RP Doran, KM (reprint author), NYU, Bellevue Hosp Ctr, Sch Med, Dept Emergency Med, First Ave & 27th St,Room A345, New York, NY 10016 USA. EM kelly.doran@nyumc.org OI Gang, Maureen/0000-0003-1747-2410 FU Robert Wood Johnson Foundation; US Department of Veterans Affairs through Clinical Scholars Program FX The study was funded by the Robert Wood Johnson Foundation and US Department of Veterans Affairs through the Clinical Scholars Program. NR 52 TC 9 Z9 9 U1 1 U2 7 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2013 VL 103 SU 2 BP S355 EP S360 DI 10.2105/AJPH.2013.301540 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AA4NP UT WOS:000331073100037 PM 24148054 ER PT J AU Fargo, JD Munley, EA Byrne, TH Montgomery, E Culhane, DP AF Fargo, Jamison D. Munley, Ellen A. Byrne, Thomas H. Montgomery, Elizabeth Culhane, Dennis P. TI Community-Level Characteristics Associated With Variation in Rates of Homelessness Among Families and Single Adults SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID NEW-YORK-CITY; RENT CONTROL; DETERMINANTS AB Objectives. We modeled rates of family and single-adult homelessness in the United States in metropolitan and nonmetropolitan regions and as a function of community-level demographic, behavioral, health, economic, and safety net characteristics. Methods. We entered community-level characteristics and US Department of Housing and Urban Development point-in-time counts for a single night in January 2009 into separate mixed-effects statistical analyses that modeled homelessness rates for 4 subpopulations: families and single adults inmetropolitan and nonmetropolitan regions. Results. Community-level factors accounted for 25% to 50% of the variance in homelessness rates across models. In metropolitan regions, alcohol consumption, social support, and several economic indicators were uniquely associated with family homelessness, and drug use and homicide were uniquely associated with single-adult homelessness. In nonmetropolitan regions, life expectancy, religious adherence, unemployment, and rent burden were uniquely associated with family homelessness, and health care access, crime, several economic indicators, and receipt of Supplemental Security Income were uniquely associated with single-adult homelessness. Conclusions. Considering homeless families and single adults separately enabled more precise modeling of associations between homelessness rates and community-level characteristics, indicating targets for interventions to reduce homelessness among these subpopulations. C1 [Fargo, Jamison D.; Munley, Ellen A.; Byrne, Thomas H.; Montgomery, Elizabeth; Culhane, Dennis P.] US Dept Vet Affairs, Natl Ctr Homelessness Among Vet, Philadelphia, PA USA. [Fargo, Jamison D.] Utah State Univ, Dept Psychol, Logan, UT 84322 USA. [Byrne, Thomas H.; Culhane, Dennis P.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. RP Fargo, JD (reprint author), Utah State Univ, Dept Psychol, 2810 Old Main Hill, Logan, UT 84322 USA. EM jamison.fargo@usu.edu FU US Department of Veterans Affairs FX We are grateful to the US Department of Veterans Affairs for the support provided to conduct this research. NR 38 TC 5 Z9 5 U1 1 U2 15 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2013 VL 103 SU 2 BP S340 EP S347 DI 10.2105/AJPH.2013.301619 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AA4NP UT WOS:000331073100035 PM 24148057 ER PT J AU Kertesz, SG Holt, CL Steward, JL Jones, RN Roth, DL Stringfellow, E Gordon, AJ Kim, TW Austin, EL Henry, SR Johnson, NK Granstaff, US O'Connell, JJ Golden, JF Young, AS Davis, LL Pollio, DE AF Kertesz, Stefan G. Holt, Cheryl L. Steward, Jocelyn L. Jones, Richard N. Roth, David L. Stringfellow, Erin Gordon, Adam J. Kim, Theresa W. Austin, Erika L. Henry, Stephen Randal Johnson, N. Kay Granstaff, U. Shanette O'Connell, James J. Golden, Joya F. Young, Alexander S. Davis, Lori L. Pollio, David E. TI Comparing Homeless Persons' Care Experiences in Tailored Versus Nontailored Primary Care Programs SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID HEALTH-CARE; PATIENT EXPERIENCE; PROSPECTIVE COHORT; LOS-ANGELES; QUALITY; PERCEPTIONS; VETERANS; PEOPLE; ADULTS; PREDICTORS AB Objectives. We compared homeless patients' experiences of care in health care organizations that differed in their degree of primary care design service tailoring. Methods. We surveyed homeless-experienced patients (either recently or currently homeless) at 3 Veterans Affairs (VA) mainstream primary care settings in Pennsylvania and Alabama, a homeless-tailored VA clinic in California, and a highly tailored non-VA Health Care for the Homeless Program in Massachusetts (January 2011-March 2012). We developed a survey, the "Primary Care Quality-Homeless Survey," to reflect the concerns and aspirations of homeless patients. Results. Mean scores at the tailored non-VA site were superior to those from the 3 mainstream VA sites (P < .001). Adjusting for patient characteristics, these differences remained significant for subscales assessing the patient-clinician relationship (P < .001) and perceptions of cooperation among providers (P = .004). There were 1.5- to 3-fold increased odds of an unfavorable experience in the domains of the patient-clinician relationship, cooperation, and access or coordination for the mainstream VA sites compared with the tailored non-VA site; the tailored VA site attained intermediate results. Conclusions. Tailored primary care service design was associated with a superior service experience for patients who experienced homelessness. C1 [Kertesz, Stefan G.; Austin, Erika L.; Johnson, N. Kay; Granstaff, U. Shanette] Birmingham VA Med Ctr, Birmingham, AL 35233 USA. [Holt, Cheryl L.] Univ Maryland, Baltimore, MD 21201 USA. [Steward, Jocelyn L.] Univ Alabama Birmingham, Birmingham, AL USA. [Jones, Richard N.] Brown Univ, Providence, RI 02912 USA. [Roth, David L.] Johns Hopkins Univ, Baltimore, MD USA. [Stringfellow, Erin] Washington Univ, St Louis, MO USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Kim, Theresa W.] Boston Med Ctr, Boston, MA USA. [Kim, Theresa W.; O'Connell, James J.] Boston Healthcare Homeless Program, Boston, MA USA. [Henry, Stephen Randal; Golden, Joya F.; Young, Alexander S.] VA Med Ctr, Los Angeles, CA USA. [Davis, Lori L.] Tuscaloosa VA Med Ctr, Tuscaloosa, AL USA. [Pollio, David E.] Univ Alabama, Tuscaloosa, AL USA. RP Kertesz, SG (reprint author), Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit, Stop Code 151,700 South 19th St, Birmingham, AL 35233 USA. EM Stefan.Kertesz@va.gov RI Jones, Richard/J-3488-2013; OI Jones, Richard/0000-0002-1049-218X; Kim, Theresa/0000-0001-6043-0721; Kertesz, Stefan/0000-0001-6101-8421 FU Department of Veterans Affairs, Health Services Research & Development Branch [IAA-07-069-2]; National Institute on Drug Abuse [T32DA01035] FX Research was funded by the Department of Veterans Affairs, Health Services Research & Development Branch (Grant IAA-07-069-2). E. Stringfellow received additional support from the National Institute on Drug Abuse (T32DA01035). NR 66 TC 7 Z9 7 U1 1 U2 13 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2013 VL 103 SU 2 BP S331 EP S339 DI 10.2105/AJPH.2013.301481 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AA4NP UT WOS:000331073100034 PM 24148052 ER PT J AU Metraux, S Clegg, LX Daigh, JD Culhane, DP Kane, V AF Metraux, Stephen Clegg, Limin X. Daigh, John D. Culhane, Dennis P. Kane, Vincent TI Risk Factors for Becoming Homeless Among a Cohort of Veterans Who Served in the Era of the Iraq and Afghanistan Conflicts SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID MENTAL-HEALTH PROBLEMS; PAST HOMELESSNESS; AFFAIRS; CARE; ASSOCIATION; DISORDERS; ATTRITION; SERVICES; ILLNESS; FEMALE AB Objectives. In this population-based cohort study, we assessed baseline risk factors for homelessness, including the role of service in the Iraq or Afghanistan conflicts, among a large cohort of recent veterans. Methods. Data for this study came from administrative records for 310 685 veterans who separated from active military duty from July 1, 2005, to September 30, 2006. We used survival analysis methods to determine incidence rates and risk factors for homelessness, based on baseline data for military factors, demographic characteristics, and diagnoses of behavioral health disorders and traumatic brain injury. Results. Service in Iraq or Afghanistan and, more specifically, posttraumatic stress disorder among veterans deployed there, were significant risk factors of modest magnitude for homelessness, and socioeconomic and behavioral health factors provided stronger indicators of risk. Gender was not a significant indicator of differential risk. Conclusions. Although service in Iraq and Afghanistan was significant, socioeconomic and behavioral health indicators show more promise in efforts to use administrative data to inform prevention efforts by identifying veterans who are at elevated risk for becoming homeless upon their return to civilian life. C1 [Metraux, Stephen; Culhane, Dennis P.; Kane, Vincent] US Dept Vet Affairs, Natl Ctr Homelessness Vet, Philadelphia, PA 19104 USA. [Metraux, Stephen] Univ Sci, Dept Hlth Policy & Publ Hlth, Philadelphia, PA USA. [Culhane, Dennis P.] Univ Penn, Sch Social Welf Policy & Practice, Philadelphia, PA 19104 USA. [Clegg, Limin X.; Daigh, John D.] US Dept Vet Affairs, Off Inspector Gen, Washington, DC USA. RP Metraux, S (reprint author), US Dept Vet Affairs, Ctr Homelessness Vet, 4200 Chester Ave,Suite 201, Philadelphia, PA 19104 USA. EM stephen.metraux@va.gov FU US Department of Veterans Affairs, National Center on Homelessness Among Veterans FX This project was funded by the US Department of Veterans Affairs, National Center on Homelessness Among Veterans. NR 36 TC 10 Z9 10 U1 2 U2 16 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2013 VL 103 SU 2 BP S255 EP S261 DI 10.2105/AJPH.2013.301432 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AA4NP UT WOS:000331073100023 PM 24148066 ER PT J AU Montgomery, AE Fargo, JD Byrne, TH Kane, V Culhane, DP AF Montgomery, Ann Elizabeth Fargo, Jamison D. Byrne, Thomas H. Kane, Vincent Culhane, Dennis P. TI Universal Screening for Homelessness and Risk for Homelessness in the Veterans Health Administration SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article AB We examined data for all veterans who completed the Veterans Health Administration's national homelessness screening instrument between October 1, 2012, and January 10, 2013. Among veterans who were not engaged with the US Department of Veterans Affairs homeless system and presented for primary care services, the prevalence of recent housing instability or homelessness was 0.9% and homelessness risk was 1.2%. Future research will refine out-reach strategies, targeting of prevention resources, and development of novel interventions. C1 [Montgomery, Ann Elizabeth; Fargo, Jamison D.; Byrne, Thomas H.; Kane, Vincent; Culhane, Dennis P.] US Dept Vet Affairs, Natl Ctr Homelessness Vet, Philadelphia, PA USA. [Fargo, Jamison D.] Utah State Univ, Dept Psychol, Logan, UT 84322 USA. [Byrne, Thomas H.; Culhane, Dennis P.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. RP Montgomery, AE (reprint author), 4100 Chester Ave,Suite 201, Philadelphia, PA 19104 USA. EM ann.montgomery2@va.gov FU US Department of Veterans Affairs, National Center on Homelessness Among Veterans FX This project was funded by the US Department of Veterans Affairs, National Center on Homelessness Among Veterans. NR 3 TC 8 Z9 8 U1 0 U2 6 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2013 VL 103 SU 2 BP S210 EP S211 DI 10.2105/AJPH.2013.301398 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AA4NP UT WOS:000331073100013 PM 24148032 ER PT J AU Russell, LM Devore, MD Barnes, SM Forster, JE Hostetter, TA Montgomery, AE Casey, R Kane, V Brenner, LA AF Russell, Leah M. Devore, Maria D. Barnes, Sean M. Forster, Jeri E. Hostetter, Trisha A. Montgomery, Ann Elizabeth Casey, Roger Kane, Vincent Brenner, Lisa A. TI Challenges Associated With Screening for Traumatic Brain Injury Among US Veterans Seeking Homeless Services SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID PREVALENCE; METAANALYSIS; HEALTH AB We identified the prevalence of traumatic brain injury (TBI) among homeless veterans and assessed the TBI-4, a screening tool created to identify TBI history. Between May 2010 and October 2011, 800 US veterans from 2 hospitals, one eastern (n = 122) and one western (n = 678) completed some or all measures. Findings suggested that 47% of veterans seeking homeless services had a probable history of TBI (data for prevalence obtained only at the western hospital). However, psychometric results from the screening measure suggested that this may be an underestimate and supported comprehensive assessment of TBI in this population. C1 [Russell, Leah M.; Devore, Maria D.; Barnes, Sean M.; Forster, Jeri E.; Hostetter, Trisha A.; Brenner, Lisa A.] 19 Mental Illness Res Educ & Clin Ctr MIRECC, VISN, Denver, CO USA. [Montgomery, Ann Elizabeth; Kane, Vincent] Vet Affairs Natl Ctr Homelessness Vet, Philadelphia, PA USA. [Casey, Roger] Vet Affairs Natl Ctr Homelessness Vet, Tampa, FL USA. RP Brenner, LA (reprint author), MIRECC, Denver VA Med Ctr, 1055 Clermont St, Denver, CO 80203 USA. EM lisa.brenner@va.gov FU National Center on Homelessness Among Veterans; VISN 19 MIRECC FX This project was funded by the National Center on Homelessness Among Veterans. Additional support was provided by the VISN 19 MIRECC. NR 12 TC 5 Z9 5 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2013 VL 103 SU 2 BP S211 EP S213 DI 10.2105/AJPH.2013.301485 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AA4NP UT WOS:000331073100014 PM 24148060 ER EF