FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Rajab, HA Baker, NL Hunt, KJ Klein, R Cleary, PA Lachin, J Virella, G Lopes-Virella, MF AF Rajab, Hussein A. Baker, Nathaniel L. Hunt, Kelly J. Klein, Richard Cleary, Patricia A. Lachin, John Virella, Gabriel Lopes-Virella, Maria F. CA DCCT EDIC Grp Investigators TI The predictive role of markers of Inflammation and endothelial dysfunction on the course of diabetic retinopathy in type 1 diabetes SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE Type I diabetes; Diabetes complications; Retinopathy; Biomarkers; E-selectin; Plasminogen activator inhibitor type 1 ID INTERVAL-CENSORED DATA; COMPLICATIONS TRIAL; ADHESION MOLECULE-1; RETINAL LEUKOSTASIS; INSULIN-RESISTANCE; PROGRESSION; COAGULATION; MELLITUS; COHORT; RISK AB Aims: This study was undertaken to determine whether levels of inflammation and endothelial dysfunction biomarkers in serum samples collected at baseline in the Diabetes Control and Complications Trial (DCCT) cohort could predict the development of retinopathy. Methods: Levels of clotting/fibrinolysis, inflammation and endothelial dysfunction biomarkers were measured in 1391 subjects with type I diabetes to determine whether their levels predicted increased risk to develop or accelerate progression of retinopathy during 16 years of follow-up. Results: Using regression models adjusted for DCCf treatment group, duration of diabetes, baseline retinopathy scores, HbA1c and albumin excretion rate, the baseline levels of sE-selectin and PAI-1 (active) were significantly associated with increased risk of a 3-step progression in retinopathy score in the primary prevention cohort (PPC). After adjusting for additional covariates ACE/ARE and statin therapy), this association persisted. Levels of active and total PAI-1 in the same group were also significantly associated, after similar adjustments, with the time to progress to severe non-proliferative retinopathy during the followup period (54 and 29%, respectively of increased risk). No associations were observed in the secondary intervention cohort for any of the outcomes. Conclusions: High levels of sE-selectin and PAI-1 are associated with the development of retinopathy in patients with uncomplicated type I diabetes. Published by Elsevier Inc. C1 [Rajab, Hussein A.; Klein, Richard; Lopes-Virella, Maria F.] Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. [Baker, Nathaniel L.; Hunt, Kelly J.] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. [Klein, Richard; Lopes-Virella, Maria F.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Cleary, Patricia A.; Lachin, John] George Washington Univ, Ctr Biostat, Washington, DC USA. [Virella, Gabriel] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. RP Lopes-Virella, MF (reprint author), 114 Doughty St, Charleston, SC 29425 USA. EM virellam@musc.edu OI Lachin, John/0000-0001-9838-2841 FU National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01-DK-081352]; Research Service of the Ralph H. Johnson Department of the Veterans Affairs Medical Center; Division of Diabetes, Endocrinology and Metabolic Diseases (NIDDK) of the National Institutes of Health; National Center for Research Resources; Genentech Inc.; NIDDK FX This work was supported by the grant R01-DK-081352 (M.F. L-V) funded by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and by the Research Service of the Ralph H. Johnson Department of the Veterans Affairs Medical Center. The DCCT/EDIC was sponsored through research contracts from the Division of Diabetes, Endocrinology and Metabolic Diseases (NIDDK) of the National Institutes of Health.; Additional support was provided by the National Center for Research Resources through the General Clinical Research Centers program and by Genentech Inc., through a Cooperative Research and Development Agreement with the NIDDK. NR 37 TC 5 Z9 5 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 EI 1873-460X J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD JAN-FEB PY 2015 VL 29 IS 1 BP 108 EP 114 DI 10.1016/j.jdiacomp.2014.08.004 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AZ5EY UT WOS:000348244400022 PM 25441222 ER PT J AU Wanner, M Houston, N Javorsky, E Yuan, MS Alora-Palli, M Kimball, AB AF Wanner, Molly Houston, Neil Javorsky, Emilia Yuan, Minsheng Alora-Palli, Maria Kimball, Alexa B. TI Single Blind, Randomized, Controlled Trial of a Lightening Product With and Without Iontophoresis Versus Tretinoin and Vehicle for Hyperpigmentation SO JOURNAL OF DRUGS IN DERMATOLOGY LA English DT Article ID PHOTODAMAGED FACIAL SKIN; PLACEBO-CONTROLLED TRIAL; TOPICAL TRETINOIN; RETINOIC ACID; EMOLLIENT CREAM; VITAMIN-C; MELASMA; PIGMENTATION; PEPTIDE; DAMAGE AB Background: Hyperpigmentation is a common concern and has many causes including lentigines and melasma. Currently available topical products for hyperpigmentation are limited by their potential for irritation, lack of demonstrated efficacy or regulatory concerns.. Objective: To compare the efficacy of a new skin lightening product with and without iontophoresis to a known effective product (tretinoin) and placebo on hyperpigmentation caused by lentigines and/or melasma. Secondary objectives included an assessment of the product's effects on the appearance of rhytides and roughness. Methods and Materials: Eighty subjects were randomized into one of four treatment groups: proprietary lightening product, proprietary lightening product with iontophoresis, tretinoin 0.05% cream, or vehicle control. Seventy-four subjects completed all study visits. Blinded assessments of subjects were performed at each visit under ambient and Wood's light. Results: The proprietary skin lightening product improved facial hyperpigmentation versus placebo under ambient light (P = 0.05) and Wood's lamp (P = 0.01) examination. Tretinoin also improved facial hyperpigmentation versus placebo under Wood's lamp (P = 0.01). The proprietary product was better tolerated than tretinoin, with fewer subject reported side effects. Conclusion: The investigational product was effective and may be better tolerated than tretinoin cream. C1 [Wanner, Molly; Yuan, Minsheng] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. [Houston, Neil] Massachusetts Gen Hosp, Dept Dermatol, Clin Unit Res Trials & Outcomes Skin CURTIS, Boston, MA 02114 USA. [Javorsky, Emilia] Univ Massachusetts, Sch Med, Worcester, MA USA. [Alora-Palli, Maria; Kimball, Alexa B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Unit Res Trials & Outcomes Skin CURTIS,Dept, Boston, MA USA. RP Wanner, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. EM mwanner@partners.org FU Nu Skin International, Inc. FX The study was funded by Nu Skin International, Inc. Dr. Kimball was a consultant for Nu Skin International, Inc at the time the study was performed. Dr. Wanner is a member of the Scientific Advisory Board and a consultant for Nu Skin International, Inc. NR 30 TC 0 Z9 0 U1 1 U2 2 PU JOURNAL OF DRUGS IN DERMATOLOGY PI NEW YORK PA 377 PARK AVE SOUTH, 6TH FLOOR, NEW YORK, NY 10016 USA SN 1545-9616 J9 J DRUGS DERMATOL JI J. Drugs Dermatol. PD JAN PY 2015 VL 14 IS 1 BP 13 EP 18 PG 6 WC Dermatology SC Dermatology GA AZ1PF UT WOS:000348009900003 PM 25607903 ER PT J AU Hindle, AG Otis, JP Epperson, LE Hornberger, TA Goodman, CA Carey, HV Martin, SL AF Hindle, Allyson G. Otis, Jessica P. Epperson, L. Elaine Hornberger, Troy A. Goodman, Craig A. Carey, Hannah V. Martin, Sandra L. TI Prioritization of skeletal muscle growth for emergence from hibernation SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE Spermophilus; Disuse atrophy; Muscle regeneration; SUnSET; Echo magnetic resonance imaging ID GROUND-SQUIRREL INTESTINE; SPERMOPHILUS-LATERALIS; PROTEIN-SYNTHESIS; MAMMALIAN HIBERNATION; LOW-TEMPERATURE; DISUSE ATROPHY; BLACK BEARS; EXPRESSION; MAINTENANCE; METABOLISM AB Mammalian hibernators provide an extreme example of naturally occurring challenges to muscle homeostasis. The annual hibernation cycle is characterized by shifts between summer euthermy with tissue anabolism and accumulation of body fat reserves, and winter heterothermy with fasting and tissue catabolism. The circannual patterns of skeletal muscle remodelling must accommodate extended inactivity during winter torpor, the motor requirements of transient winter active periods, and sustained activity following spring emergence. Muscle volume in thirteen-lined ground squirrels (Ictidomys tridecemlineatus) calculated from MRI upper hindlimb images (n=6 squirrels, n=10 serial scans) declined from hibernation onset, reaching a nadir in early February. Paradoxically, mean muscle volume rose sharply after February despite ongoing hibernation, and continued total body mass decline until April. Correspondingly, the ratio of muscle volume to body mass was steady during winter atrophy (October-February) but increased (+70%) from February to May, which significantly outpaced changes in liver or kidney examined by the same method. Generally stable myocyte cross-sectional area and density indicated that muscle remodelling is well regulated in this hibernator, despite vastly altered seasonal fuel and activity levels. Body composition analysis by echo MRI showed lean tissue preservation throughout hibernation amid declining fat mass by the end of winter. Muscle protein synthesis was 66% depressed in early but not late winter compared with a summer fasted baseline, while no significant changes were observed in the heart, liver or intestine, providing evidence that could support a transition in skeletal muscle regulation between early and late winter, prior to spring emergence and re-feeding. C1 [Hindle, Allyson G.; Epperson, L. Elaine; Martin, Sandra L.] Univ Colorado, Sch Med, Aurora, CO 80045 USA. [Otis, Jessica P.; Hornberger, Troy A.; Goodman, Craig A.; Carey, Hannah V.] Univ Wisconsin, Sch Vet Med, Madison, WI 53706 USA. RP Hindle, AG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM ahindle@mgh.harvard.edu OI Hornberger, Troy/0000-0002-2349-1899; Goodman, Craig/0000-0002-5874-7743 FU National Institutes of Health [R01HL-89049, R01 AR057347]; University of Wisconsin-Madison School of Veterinary Medicine; NIH [P30 CA046934, UL1 TR001082] FX This work was supported by the National Institutes of Health (R01HL-89049 to S.L.M., R01 AR057347 to T.A.H.) and the University of Wisconsin-Madison School of Veterinary Medicine (to H.V.C.). MRI images were collected in the Animal Imaging and Metabolomics Shared Resources Core facility, supported in part by NIH grants to the University of Colorado Cancer Center (P30 CA046934) and the Colorado Clinical and Translational Sciences Institute (UL1 TR001082). Quantitative magnetic resonance imaging was supported by the Colorado Nutrition and Obesity Research (NORC) NIH P30 DK048520. Deposited in PMC for release after 12 months. NR 50 TC 10 Z9 10 U1 1 U2 30 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0022-0949 EI 1477-9145 J9 J EXP BIOL JI J. Exp. Biol. PD JAN PY 2015 VL 218 IS 2 BP 276 EP 284 DI 10.1242/jeb.109512 PG 9 WC Biology SC Life Sciences & Biomedicine - Other Topics GA AZ5US UT WOS:000348286900022 PM 25452506 ER PT J AU Cerulli, C Trabold, N Kothari, CL Dichter, ME Raimondi, C Lucas, J Cobus, A Rhodes, KV AF Cerulli, Catherine Trabold, Nicole Kothari, Catherine L. Dichter, Melissa E. Raimondi, Christina Lucas, Janine Cobus, Alex Rhodes, Karin V. TI In Our Voice: Survivors' Recommendations for Change SO JOURNAL OF FAMILY VIOLENCE LA English DT Article DE Intimate partner violence; Reform court procedures; Socio-ecological model ID INTIMATE PARTNER VIOLENCE; COORDINATED COMMUNITY RESPONSES; DOMESTIC VIOLENCE; PROTECTION ORDERS; HEALTH-CARE; INTERVENTION; ARREST; BATTERERS; SERVICES; ASSAULT AB Seven focus groups with a diverse group of intimate partner violence (IPV) survivors (n = 39) explored how to improve survivor satisfaction, empowerment, and safety related to their court-based experiences. These occurred in three jurisdictions which all supported community coordinated responses to IPV. This paper contributes to the literature by asking survivors about existing service gaps and how helping professionals might enhance court operations. Analysis was conducted using a framework approach based on the socio-ecological model. Findings suggest four areas worthy of improvement: Logistics, Emotional Enhancements, Society's Perception of IPV, and Court Procedures. The recommendations for change are neither expensive nor complicated; rather, modest changes may result in greater victim satisfaction with the courts. C1 [Cerulli, Catherine; Raimondi, Christina] Univ Rochester, Med Ctr, Dept Psychiat, Rochester, NY 14642 USA. [Trabold, Nicole] Univ Rochester, Med Ctr, Sch Nursing, Rochester, NY 14642 USA. [Kothari, Catherine L.] Michigan State Univ, Kalamazoo Ctr Med Studies, E Lansing, MI 48824 USA. [Dichter, Melissa E.] Philadelphia VA Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA 19104 USA. [Lucas, Janine] Alternat Battered Women Inc, Rochester, NY USA. [Rhodes, Karin V.] Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 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 41 TC 1 Z9 1 U1 3 U2 12 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7482 EI 1573-2851 J9 J FAM VIOLENCE JI J. Fam. Violence PD JAN PY 2015 VL 30 IS 1 BP 75 EP 83 DI 10.1007/s10896-014-9657-7 PG 9 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA AZ2GC UT WOS:000348051500007 ER PT J AU Gutierrez, JC Terwiesch, C Pelak, M Pettit, AR Marcus, SC AF Gutierrez, Jennifer C. Terwiesch, Christian Pelak, Mary Pettit, Amy R. Marcus, Steven C. TI Characterizing Primary Care Visit Activities at Veterans Health Administration Clinics SO JOURNAL OF HEALTHCARE MANAGEMENT LA English DT Article ID PATIENT-CARE; OFFICE VISITS; TIME; PHYSICIANS; US AB Medical home models seek to increase efficiency and maximize the use of resources by ensuring that all care team members work at the top of their licenses. We sought to break down primary care office visits into measurable activities to better understand how primary care providers (PCPs) currently spend visit time and to provide insight into potential opportunities for revision or redistribution of healthcare tasks. We videotaped 27 PCPs during office visits with 121 patients at four Veterans Health Administration medical centers. Based on patterns emerging from the data, we identified a taxonomy of 12 provider activity categories that enabled us to quantify the frequency and duration of activities occurring during routine primary care visits. We conducted descriptive and multivariate analyses to examine associations between visit characteristics and provider and clinic characteristics. We found that PCPs spent the greatest percentage of their visit time discussing existing conditions (20%), discussing new conditions (18%), record keeping (13%), and examining patients (13%). Providers spent the smallest percentage of time on preventive care and coordination of care. Mean visit length was 22.9 minutes (range 7.9-58.0 minutes). Site-level ratings of medical home implementation were not associated with differences in how visit time was spent. These data provide a window into how PCPs are spending face-to-face time with patients. The methodology and taxonomy presented here may prove useful for future quality improvement and research endeavors, particularly those focused on opportunities to increase nonappointment care and to ensure that team members work at the top of their skill level. C1 [Gutierrez, Jennifer C.] Philadelphia Vet Affairs Med Ctr, CEPACT, Philadelphia, PA 19104 USA. [Terwiesch, Christian] Univ Penn, CEPACT, Philadelphia, PA 19104 USA. [Terwiesch, Christian] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [Terwiesch, Christian] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Marcus, Steven C.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. RP Gutierrez, JC (reprint author), Philadelphia Vet Affairs Med Ctr, CEPACT, Philadelphia, PA 19104 USA. EM jennifer.gutierrez@va.gov NR 23 TC 2 Z9 2 U1 2 U2 3 PU AMER COLL HEALTHCARE EXEC HEALTH ADMINISTRATION PRESS PI CHICAGO PA ONE NORTH FRANKLIN ST SUITE 1700, CHICAGO, IL 60606 USA SN 1096-9012 EI 1944-7396 J9 J HEALTHC MANAG JI J. Healthc. Manag. PD JAN-FEB PY 2015 VL 60 IS 1 BP 30 EP 42 PG 13 WC Health Policy & Services SC Health Care Sciences & Services GA AZ5KM UT WOS:000348260000007 PM 26529991 ER PT J AU Peev, MP Yeh, DD Quraishi, SA Osler, P Chang, YC Gillis, E Albano, CE Darak, S Velmahos, GC AF Peev, Miroslav P. Yeh, D. Dante Quraishi, Sadeq A. Osler, Polina Chang, Yuchiao Gillis, Erin Albano, Caitlin E. Darak, Sharon Velmahos, George C. TI Causes and Consequences of Interrupted Enteral Nutrition: A Prospective Observational Study in Critically Ill Surgical Patients SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Article DE malnutrition; caloric debt; ICU nutrition; critical illness ID INTENSIVE-CARE-UNIT; PROTEIN-ENERGY PROVISION; HOSPITAL STAY; PROTOCOL; IMPACT; MALNUTRITION; DELIVERY; THERAPY; LENGTH; ICU AB Background: Malnutrition and underfeeding are major challenges in caring for critically ill patients. Our goal was to characterize interruptions in enteral nutrition (EN) delivery and their impact on caloric debt in the surgical intensive care unit (ICU). Materials and Methods: We performed a prospective, observational study of adults admitted to surgical ICUs at a Boston teaching hospital (March-December 2012). We categorized EN interruptions as unavoidable vs avoidable and compared caloric deficit between patients with 1 EN interruption (group 1) vs those without interruptions (group 2). Multivariable logistic regression was used to investigate the association of EN interruption with the risk of underfeeding. Poisson regression was used to investigate the association of EN interruption with length of stay (LOS) and mortality. Results: Ninety-four patients comprised the analytic cohort. Twenty-six percent of interruptions were deemed avoidable. Group 1 (n = 64) had a significantly higher mean daily and cumulative caloric deficit vs group 2 (n = 30). Patients in group 1 were at a 3-fold increased risk of being underfed (adjusted odds ratio, 2.89; 95% confidence interval [CI], 1.03-8.11), had a 30% higher risk of prolonged ICU LOS (adjusted incident risk ratio [IRR], 1.27; 95% CI, 1.14-1.42), and had a 50% higher risk of prolonged hospital LOS (adjusted IRR, 1.53; 95% CI, 1.41-1.67) vs group 2. Conclusions: In our cohort of critically ill surgical patients, EN interruption was frequent, largely unavoidable, and associated with undesirable outcomes. Future efforts to optimize nutrition in the surgical ICU may benefit from considering strategies that maximize nutrient delivery before and after clinically appropriate EN interruptions. C1 [Peev, Miroslav P.; Yeh, D. Dante; Osler, Polina; Velmahos, George C.] Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Peev, Miroslav P.; Yeh, D. Dante; Velmahos, George C.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Quraishi, Sadeq A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Quraishi, Sadeq A.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Chang, Yuchiao] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Gillis, Erin; Albano, Caitlin E.; Darak, Sharon] Massachusetts Gen Hosp, Dept Nutr & Food Serv, Boston, MA 02114 USA. RP Yeh, DD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Surg, 165 Cambridge St,810, Boston, MA 02114 USA. EM dyeh2@partners.org FU NIH [5T32GM007592-33] FX S.A.Q. received support from NIH 5T32GM007592-33. NR 31 TC 11 Z9 11 U1 3 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0148-6071 EI 1941-2444 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD JAN PY 2015 VL 39 IS 1 BP 21 EP 27 DI 10.1177/0148607114526887 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AZ3GF UT WOS:000348114800002 PM 24714361 ER PT J AU Quraishi, SA Litonjua, AA Moromizato, T Gibbons, FK Camargo, CA Giovannucci, E Christopher, KB AF Quraishi, Sadeq A. Litonjua, Augusto A. Moromizato, Takuhiro Gibbons, Fiona K. Camargo, Carlos A., Jr. Giovannucci, Edward Christopher, Kenneth B. TI Association Between Prehospital Vitamin D Status and Hospital-Acquired Clostridium difficile Infections SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Article DE vitamin D; 25-hydroxyvitamin D; Clostridium difficile; hospital-acquired infection; nosocomial infection ID LOCALLY WEIGHTED REGRESSION; ANTIMICROBIAL PEPTIDES; D DEFICIENCY; CARE PATIENTS; DISEASE; MORTALITY; RISK; DIARRHEA; INSUFFICIENCY; COMORBIDITY AB Objective: To investigate whether preadmission 25-hydroxyvitamin D (25(OH)D) levels are associated with the risk of hospital-acquired Clostridium difficile infection (HACDI). Materials and Methods: Our retrospective cohort study focused on 568 adult patients from 2 Boston teaching hospitals between August 1993 and November 2006. All patients had 25(OH)D levels measured before hospitalization and were at risk for HACDI (defined as the presence of C difficile toxin A or B in stool samples obtained >48 hours after hospitalization). We performed multivariable regression analyses to test the association of prehospital 25(OH)D levels with HACDI while adjusting for clinically relevant covariates. Results: In these 568 patients, mean (SD) 25(OH)D level was 19 (12) ng/mL, and 11% of patients met criteria for incident HACDI. Following adjustment for age, sex, race (nonwhite vs white), patient type (medical vs surgical), and Deyo-Charlson index, patients with 25(OH)D levels <10 ng/mL had higher odds of HACDI (odds ratio [OR], 2.90; 95% confidence interval [CI], 1.01-8.34) compared with patients with 25(OH)D levels 30 ng/mL. When patients with HACDI were analyzed relative to a larger patient cohort without HACDI (n = 5047), those with 25(OH)D levels <10 ng/mL (OR, 4.96; 95% CI, 1.84-13.38) and 10-19.9 ng/mL (OR, 3.36; 95% CI, 1.28-8.85) had higher adjusted odds of HACDI compared with patients with 25(OH)D levels 30 ng/mL. Conclusions: In our cohort of adult patients, vitamin D status before hospital admission was inversely associated with the risk of developing HACDI. These data support the need for randomized, controlled trials to test the role of vitamin D supplementation to prevent HACDI. C1 [Quraishi, Sadeq A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Litonjua, Augusto A.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Litonjua, Augusto A.] Brigham & Womens Hosp, Dept Med, Pulm & Crit Care Div, Boston, MA 02115 USA. [Moromizato, Takuhiro; Christopher, Kenneth B.] Brigham & Womens Hosp, Dept Med, Div Renal, Nathan E Hellman Mem Lab, Boston, MA 02115 USA. [Gibbons, Fiona K.] Massachusetts Gen Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Christopher, KB (reprint author), Brigham & Womens Hosp, Dept Med, Div Renal, Nathan E Hellman Mem Lab, 75 Francis St,MRB 418, Boston, MA 02115 USA. EM kbchristopher@partners.org FU National Institutes of Health [5T32GM007592-33, UL1 RR025758, R01 AI093723, U01 AI087881, K08AI060881] FX This study was support by 5T32GM007592-33 and UL1 RR025758 (S.A.Q.), R01 AI093723 and U01 AI087881 (C.A.C.), and K08AI060881 (K.B.C.) from the National Institutes of Health. NR 56 TC 10 Z9 10 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0148-6071 EI 1941-2444 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD JAN PY 2015 VL 39 IS 1 BP 47 EP 55 DI 10.1177/0148607113511991 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AZ3GF UT WOS:000348114800005 PM 24492311 ER PT J AU Anderson, KS Cramer, DW Sibani, S Wallstrom, G Wong, J Park, J Qiu, J Vitonis, A LaBaer, J AF Anderson, Karen S. Cramer, Daniel W. Sibani, Sahar Wallstrom, Garrick Wong, Jessica Park, Jin Qiu, Ji Vitonis, Allison LaBaer, Joshua TI Autoantibody Signature for the Serologic Detection of Ovarian Cancer SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE Ovarian cancer; autoantibodies; biomarker; proteomics; protein microarrays ID TUMOR-ASSOCIATED ANTIGENS; PROTEIN MICROARRAYS; BREAST-CANCER; PROSTATE-CANCER; EXPRESSION; RECEPTOR; CELLS; GENE; BIOMARKERS; ARRAYS AB Sera from patients with ovarian cancer contain autoantibodies (AAb) to tumor-derived proteins that are potential biomarkers for early detection. To detect AAb, we probed high-density programmable protein microarrays (NAPPA) expressing 5177 candidate tumor antigens with sera from patients with serous ovarian cancer (n = 34 cases/30 controls) and measured bound IgG. Of these, 741 antigens were selected and probed with an independent set of ovarian cancer sera (n = 60 cases/60 controls). Twelve potential autoantigens were identified with sensitivities ranging from 13 to 22% at >93% specificity. These were retested using a Luminex bead array using 60 cases and 60 controls, with sensitivities ranging from 0 to 31.7% at 95% specificity. Three AAb (p53, PTPRA, and PTGFR) had area under the curve (AUC) levels >60% (p < 0.01), with the partial AUC (SPAUC) over 5 times greater than for a nondiscriminating test (p < 0.01). Using a panel of the top three AAb (p53, PTPRA, and PTGFR), if at least two AAb were positive, then the sensitivity was 23.3% at 98.3% specificity. AAb to at least one of these top three antigens were also detected in 7/20 sera (35%) of patients with low CA 125 levels and 0/15 controls. AAb to p53, PTPRA, and PTGFR are potential biomarkers for the early detection of ovarian cancer. C1 [Anderson, Karen S.; Wallstrom, Garrick; Park, Jin; Qiu, Ji; LaBaer, Joshua] Arizona State Univ, Biodesign Inst, Ctr Personalized Diagnost, Tempe, AZ 85287 USA. [Cramer, Daniel W.; Vitonis, Allison] Brigham & Womens Hosp, Dept Gynecol & Reprod Biol, Boston, MA 02115 USA. [Sibani, Sahar] Harvard Univ, Sch Med, Harvard Inst Prote, Boston, MA 02115 USA. [Wong, Jessica] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. RP Anderson, KS (reprint author), Arizona State Univ, Biodesign Inst, Ctr Personalized Diagnost, Tempe, AZ 85287 USA. EM karen.anderson.1@asu.edu FU Early Detection Research Network [U01 CA117374, UO1 CA086381] FX This study was supported by a research grant from the Early Detection Research Network U01 CA117374 (K.S.A. and J.L.) and UO1 CA086381 (D.W.C). NR 45 TC 16 Z9 16 U1 4 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 EI 1535-3907 J9 J PROTEOME RES JI J. Proteome Res. PD JAN PY 2015 VL 14 IS 1 BP 578 EP 586 DI 10.1021/pr500908n PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA AY3UA UT WOS:000347506600051 PM 25365139 ER PT J AU Liang, F Rudnicki, PA Prince, NH Lipsitz, S May, JW Guo, LF AF Liang, Fan Rudnicki, Pamela A. Prince, Noah H. Lipsitz, Stuart May, James W., Jr. Guo, Lifei TI An Evaluation of Plastic Surgery Resident Selection Factors SO JOURNAL OF SURGICAL EDUCATION LA English DT Article DE plastic surgery; residency application; surgical education ID MEDICAL-SCHOOL; PERFORMANCE; CRITERIA AB OBJECTIVE: Our purpose was to provide a metric by which evaluation criteria are prioritized during resident selection. In this study, we assessed which residency applicant qualities are deemed important by members of the American Association of Plastic Surgeons (AAPS). METHODS: A survey was distributed to all 580 AAPS members, and 295 responded to rate the importance of resident metrics, including measures of competency and personal characteristics. Demographic information, background training, and interaction with residents were also noted. Using SAS v9.2 (SAS Institute, Cary, NC), outcomes were analyzed across demographic groups with column trend exact (GTE) test for ordinal variables, Mantel-Haenszel trend test for interval variables, and Fisher exact test for discrete variables. RESULTS: Regarding competency metrics, letters of recommendation from known sources is the most important factor, whereas letters from unknown sources ranks the lowest. Character evaluations identified honesty as the most desirable trait; dishonesty was the most despised. Across demographic groups, academic surgeons and program directors value letters from known sources more than nonacademicians or nonprogram directors (GTE p = 0.005 and 0.002, respectively). Academicians and current program directors regard research more highly than their counterparts do (CTE p = 0.022 and 0.022, respectively). Currently, practicing surgeons, academicians, and program directors value hard work more than others (GTE p = 0.008, 0.033, and 0.029, respectively). Program directors emphasize maturity and patient commitment and are less tolerant of narcissism (GTE p = 0.002, 0.005, and 0.003, respectively). Lastly, academic surgeons and program directors look more favorably upon strong team players (GTE p < 0.00001 and p = 0.008, respectively), but less so over time (Mantel-Haenszel trend p = 0.006). CONCLUSIONS: We have examined applicant metrics that were deemed important by AAPS members and assessed their demographic interpretation. We hope this article provides a framework for plastic surgery resident selection and a guide for applicants to ascertain which qualities are highly regarded by programs. Although these attributes are highly desirable, future studies could identify if they are predictive of successful and productive plastic surgery residencies and careers. (C) 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved. C1 [Liang, Fan] Univ So Calif, Div Plast Surg, Los Angeles, CA USA. [Rudnicki, Pamela A.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Prince, Noah H.] Univ Florida, Div Plast Surg, Gainesville, FL USA. [Lipsitz, Stuart] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Biostat Serv, Boston, MA 02115 USA. [May, James W., Jr.] Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. [Guo, Lifei] Lahey Hosp & Med Ctr, Dept Plast Surg, Burlington, MA 01805 USA. RP Guo, LF (reprint author), Lahey Hosp & Med Ctr, Dept Plast Surg, 41 Mall Rd,6W, Burlington, MA 01805 USA. EM lifei.guo@lahey.org NR 10 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1931-7204 EI 1878-7452 J9 J SURG EDUC JI J. Surg. Educ. PD JAN-FEB PY 2015 VL 72 IS 1 BP 8 EP 15 DI 10.1016/j.jsurg.2014.07.013 PG 8 WC Education, Scientific Disciplines; Surgery SC Education & Educational Research; Surgery GA AZ5GS UT WOS:000348248900002 PM 25218369 ER PT J AU Pomposelli, T Hart, J Elliott, B Robison, J Brothers, T AF Pomposelli, Thomas Hart, Joseph Elliott, Bruce Robison, Jacob Brothers, Thomas TI Estimation of Mortality Risk for Vascular Operations by Trainees vs Attending Surgeons SO JOURNAL OF SURGICAL EDUCATION LA English DT Article DE vascular; surgery; education; mortality; training ID QUALITY IMPROVEMENT PROGRAM; SURGICAL QUALITY; POSTOPERATIVE MORBIDITY; ADJUSTMENT; RESIDENTS; FACULTY AB OBJECTIVE: The development of the ability to estimate patient mortality preoperatively in surgical trainees has not been well studied. DESIGN: Prospective comparative study in which the expected perioperative mortality risk and the maximum tolerable mortality at which operation would still be offered were estimated by the operating surgeons immediately before planned vascular procedures. SETTING: University vascular surgery teaching service. PARTICIPANTS: Predicted and maximum allowable mortality risks were compared between trainees and attending surgeons, with the mortality calculated using the Veterans Administration Surgical Quality Improvement Program (VASQIP) as a reference. RESULTS: Surveys were performed before 379 procedures over a 10-month period. The median expected mortality risk predicted by trainees (2%; interquartile range [IQR]: 1%-5%) was higher than the risk predicted by attending surgeons (1%; IQR: 0.8%-3%) (p < 0.01). The median expected mortality risk calculated by VASQIP (0.8%; IQR: 0.4%-1.7%) was less than that estimated by trainees by a median of 0.3% (IQR: 0.2%-3.2%) or and that by attending surgeons by 0.3% (IQR: 0.2-1.3%) (p < 0.01). The median maximum tolerable mortality risk predicted by trainees (10%; IQR: 5%-27.5%) was equal to the risk predicted by attending surgeons (10%; IQR: 5%-17.5%). The perioperative mortality calculated by VASQIP exceeded the maximum tolerable mortality offered by trainees or attending surgeons in 1% of cases each. Discrepancies between expected mortality and maximum tolerable mortality for trainees and attending surgeons were greater for younger (postgraduate year 1 or 2) trainees (0.8%; IQR: 0-3.0%) than for more senior (postgraduate year 4 or 5) trainees (0.4%; IQR: 0.1%-2.0%). CONCLUSION: Surgeons in training overestimated the perioperative mortality risk of operations and were willing to tolerate a greater mortality risk compared with attending surgeons. Both trainee and attending surgeons tended to overestimate the perioperative mortality risk compared with that calculated by VASQIP. (C) 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved. C1 [Pomposelli, Thomas; Hart, Joseph; Elliott, Bruce; Robison, Jacob; Brothers, Thomas] Med Univ S Carolina, Div Vasc Surg, Charleston, SC 29425 USA. [Brothers, Thomas] Ralph H Johnson VA Med Ctr, Dept Vet Affairs, Charleston, SC USA. RP Brothers, T (reprint author), 25 Courtenay Dr,Suite 7018, Charleston, SC 29425 USA. EM brothete@musc.edu NR 16 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1931-7204 EI 1878-7452 J9 J SURG EDUC JI J. Surg. Educ. PD JAN-FEB PY 2015 VL 72 IS 1 BP 68 EP 72 DI 10.1016/j.jsurg.2014.07.007 PG 5 WC Education, Scientific Disciplines; Surgery SC Education & Educational Research; Surgery GA AZ5GS UT WOS:000348248900011 PM 25498880 ER PT J AU Gray, WA Feiring, A Cioppi, M Hibbard, R Gray, B Khatib, Y Jessup, D Bachinsky, W Rivera, E Tauth, J Patarca, R Massaro, J Stoll, HP Jail, MR AF Gray, William A. Feiring, Andrew Cioppi, Marco Hibbard, Robert Gray, Bruce Khatib, Yazan Jessup, David Bachinsky, William Rivera, Ernesto Tauth, Jeffrey Patarca, Roberto Massaro, Joe Stoll, Hans-Peter Jail, Michael R. CA STROLL Study Investigators TI SMART Self-Expanding Nitinol Stent for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery (STROLL): 1-Year Outcomes SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; BALLOON ANGIOPLASTY; PROXIMAL POPLITEAL; OCCLUSIVE DISEASE; CLINICAL-TRIALS; ELUTING STENTS; IMPLANTATION; FRACTURES; LENGTH AB Purpose: To assess safety and efficacy of the S.M.A.R.T. Vascular Stent System (Cordis Corp, Fremont, California) in obstructive superficial femoral artery (SFA) disease. Materials and Methods: The single-arm, multicenter STROLL study (S.M.A.R.T. Nitinol Self-Expanding Stent in the Treatment of Obstructive Superficial Femoral Artery Disease) included 250 patients (250 lesions in SFA or proximal popliteal artery). The efficacy endpoint was primary patency defined by freedom from binary restenosis (peak systolic velocity ratio > 2.5) as derived by duplex ultrasound plus clinically driven target lesion revascularization (TLR) at 12 months. Results: Mean age of patients was 67.7 years +/- 10.3; 47.2% of patients had diabetes; distribution of Rutherford/Becker classes 2, 3, and 4 was 45.8%, 51.4%, and 2.8%. Mean lesion length and reference vessel diameter were 77.3 mm +/- 35.3 and 4.9 mm +/- 0.7, respectively (23.6% cases with total occlusions). The 30-day freedom from major adverse events (death, index limb amputation, clinically driven TIA) was 100%. The 1-year primary patency was 81.7% by Kaplan-Meier estimate. The presence of diabetes or total occlusion had no effect on primary patency. Ankle-brachial index was 0.4-0.8 in 84.6% of patients at baseline and improved to > 08 in 81.0% of patients at 12 months. The proportion of patients in Rutherford/Becker class 3-4 was reduced from 54.2% at baseline to 8.0% at 12 months. Four patients (2.0%) experienced single-stent strut fracture (type I) at 1 year, without associated loss of stent patency. Conclusions: The S.M.A.R.T. Vascular Stent System proved to be safe and effective for endovascular treatment of obstructive SFA and proximal popliteal artery disease, based on 1-year vessel patency and associated hemodynamic and clinical improvements. C1 [Gray, William A.] New York Presbyterian Hosp, Columbia Presbyterian Med Ctr, Dept Cardiol, New York, NY 10032 USA. [Feiring, Andrew] Columbia St Marys Hosp, Div Cardiac & Vasc Intervent, Milwaukee, WI USA. [Cioppi, Marco] Vasc Surg Associates, Dept Surg, Huntsville, AL USA. [Hibbard, Robert] Bryan LGH Heart Inst, Cardiac Catheterizat & Endovasc Labs, Lincoln, NE USA. [Gray, Bruce] Greenville Gen Hosp, Dept Surg, Greenville, SC USA. [Khatib, Yazan] First Coast Cardiovasc Inst, Dept Cardiol Endovasc, Jacksonville, FL USA. [Jessup, David] PeaceHealth St Joseph Med Ctr, Dept Cardiol, Bellingham, WA USA. [Bachinsky, William] PinnacleHealth CardioVasc Inst, Dept Cardiovasc Med, Moffitt Heart & Vasc Grp, Wormleysburg, PA USA. [Rivera, Ernesto] Amarillo Heart Clin Res Inst, Dept Cardiol, Amarillo, TX USA. [Tauth, Jeffrey] Tri Lakes Res, Dept Cardiol, Hot Springs, AZ USA. [Patarca, Roberto; Stoll, Hans-Peter] Cordis Clin Res, Dept Clin Res, Bridgewater, NJ USA. [Massaro, Joe] Harvard Clin Res Inst, Dept Biostat, Boston, MA USA. [Jail, Michael R.] Massachusetts Gen Hosp, Vasc Ultrasound Core Lab, Boston, MA 02114 USA. RP Gray, WA (reprint author), New York Presbyterian Hosp, Columbia Presbyterian Med Ctr, Dept Cardiol, 161 Ft Washington Ave, New York, NY 10032 USA. EM wg2131@cumc.columbia.edu FU Cordis FX D.J. is a paid consultant for Abbott, Cordis, Gore, and Angiosculpt. W.A.G. is a paid consultant for Cordis/J&J. Y.K. is on the endovascular advisory board at Bayer and is a speaker for Gore Medical. J.M. is an employee of HCRI who conducted the statistical analysis. R P and H.P.S. were employees of Cordis. M.R.J. is a noncompensated advisor to Abbott Vascular, Boston Scientific, Cordis Corporation, Covidien Vascular, and Medtronic Vascular, has an equity interest in PQ Bypass; and is a board member of VIVA Physicians, a 501 c 3 not-for-profit education and research organization. The STROLL study was funded by Cordis. None of the other authors have identified a conflict of interest NR 27 TC 8 Z9 8 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD JAN PY 2015 VL 26 IS 1 BP 21 EP 28 DI 10.1016/j.jvir.2014.09.018 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA AY7MM UT WOS:000347744200004 PM 25454735 ER PT J AU Nguyen, J Moteabbed, M Paganetti, H AF Nguyen, J. Moteabbed, M. Paganetti, H. TI Assessment of uncertainties in radiation-induced cancer risk predictions at clinically relevant doses SO MEDICAL PHYSICS LA English DT Article DE radiation induced cancer; risk modeling ID BREAST-CANCER; CHILDHOOD-CANCER; 2ND CANCERS; CONTRALATERAL BREAST; HODGKINS-DISEASE; CERVICAL-CANCER; PROTON THERAPY; NERVOUS-SYSTEM; THYROID-CANCER; SOLID TUMORS AB Purpose: Theoretical dose-response models offer the possibility to assess second cancer induction risks after external beam therapy. The parameters used in these models are determined with limited data from epidemiological studies. Risk estimations are thus associated with considerable uncertainties. This study aims at illustrating uncertainties when predicting the risk for organ-specific second cancers in the primary radiation field illustrated by choosing selected treatment plans for brain cancer patients. Methods: A widely used risk model was considered in this study. The uncertainties of the model parameters were estimated with reported data of second cancer incidences for various organs. Standard error propagation was then subsequently applied to assess the uncertainty in the risk model. Next, second cancer risks of five pediatric patients treated for cancer in the head and neck regions were calculated. For each case, treatment plans for proton and photon therapy were designed to estimate the uncertainties (a) in the lifetime attributable risk (LAR) for a given treatment modality and (b) when comparing risks of two different treatment modalities. Results: Uncertainties in excess of 100% of the risk were found for almost all organs considered. When applied to treatment plans, the calculated LAR values have uncertainties of the same magnitude. A comparison between cancer risks of different treatment modalities, however, does allow statistically significant conclusions. In the studied cases, the patient averaged LAR ratio of proton and photon treatments was 0.35, 0.56, and 0.59 for brain carcinoma, brain sarcoma, and bone sarcoma, respectively. Their corresponding uncertainties were estimated to be potentially below 5%, depending on uncertainties in dosimetry. Conclusions: The uncertainty in the dose-response curve in cancer risk models makes it currently impractical to predict the risk for an individual external beam treatment. On the other hand, the ratio of absolute risks between two modalities is less sensitive to the uncertainties in the risk model and can provide statistically significant estimates. (c) 2015 American Association of Physicists in Medicine. C1 [Nguyen, J.; Moteabbed, M.; Paganetti, H.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Nguyen, J.] Heidelberg Univ, Dept Phys, D-69117 Heidelberg, Germany. [Moteabbed, M.; Paganetti, H.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Paganetti, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM hpaganetti@mgh.harvard.edu FU Federal Share of program by Massachusetts General Hospital [C06 CA059267]; Proton Therapy Research, and Treatment Center FX The project was supported by the Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research, and Treatment Center. NR 49 TC 9 Z9 9 U1 1 U2 5 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JAN PY 2015 VL 42 IS 1 BP 81 EP 89 DI 10.1118/1.4903272 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AZ0TJ UT WOS:000347957200008 PM 25563249 ER PT J AU Moteabbed, M Sharp, GC Wang, Y Trofimov, A Efstathiou, JA Lu, HM AF Moteabbed, M. Sharp, G. C. Wang, Y. Trofimov, A. Efstathiou, J. A. Lu, H. -M. TI Validation of a deformable image registration technique for cone beam CT-based dose verification SO MEDICAL PHYSICS LA English DT Article DE deformable image registration; cone-beam CT; image-guided; prostate radiotherapy ID ADAPTIVE RADIATION-THERAPY; HEAD-AND-NECK; COMPUTED-TOMOGRAPHY CBCT; PROSTATE-CANCER; QUANTITATIVE-EVALUATION; CALCULATION ACCURACY; ELECTRON-DENSITY; PLANNING CT; RADIOTHERAPY; FEASIBILITY AB Purpose: As radiation therapy evolves toward more adaptive techniques, image guidance plays an increasingly important role, not only in patient setup but also in monitoring the delivered dose and adapting the treatment to patient changes. This study aimed to validate a method for evaluation of delivered intensity modulated radiotherapy (IMRT) dose based on multimodal deformable image registration (DIR) for prostate treatments. Methods: A pelvic phantom was scanned with CT and cone-beam computed tomography (CBCT). Both images were digitally deformed using two realistic patient-based deformation fields. The original CT was then registered to the deformed CBCT resulting in a secondary deformed CT. The registration quality was assessed as the ability of the DIR method to recover the artificially induced deformations. The primary and secondary deformed CT images as well as vector fields were compared to evaluate the efficacy of the registration method and it's suitability to be used for dose calculation PLASTIMATCH, a free and open source software was used for deformable image registration. A B-spline algorithm with optimized parameters was used to achieve the best registration quality. Geometric image evaluation was performed through voxel-based Hounsfield unit (HU) and vector field comparison. For dosimetric evaluation, IMRT treatment plans were created and optimized on the original CT image and recomputed on the two warped images to be compared. The dose volume histograms were compared for the warped structures that were identical in both warped images. This procedure was repeated for the phantom with full, half full, and empty bladder. Results: The results indicated mean HU differences of up to 120 between registered and ground-truth deformed CT images. However, when the CBCT intensities were calibrated using a region of interest (ROI)-based calibration curve, these differences were reduced by up to 60%. Similarly, the mean differences in average vector field lengths decreased from 10.1 to 2.5 mm when CBCT was calibrated prior to registration. The results showed no dependence on the level of bladder filling. In comparison with the dose calculated on the primary deformed CT, differences in mean dose averaged over all organs were 0.2% and 3.9% for dose calculated on the secondary deformed CT with and without CBCT calibration, respectively, and 0.5% for dose calculated directly on the calibrated CBCT, for the full-bladder scenario. Gamma analysis for the distance to agreement of 2 mm and 2% of prescribed dose indicated a pass rate of 100% for both cases involving calibrated CBCT and on average 86% without CBCT calibration. Conclusions: Using deformable registration on the planning CT images to evaluate the IMRT dose based on daily CBCTs was found feasible. The proposed method will provide an accurate dose distribution using planning CT and pretreatment CBCT data, avoiding the additional uncertainties introduced by CBCT inhomogeneity and artifacts. This is a necessary initial step toward future image-guided adaptive radiotherapy of the prostate. (c) 2015 American Association of Physicists in Medicine. C1 [Moteabbed, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Moteabbed, M (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM mmoteabbed@partners.org FU Federal Share of Program by Massachusetts General Hospital [C06 CA059267]; Proton Therapy Research and Treatment Center FX This project was supported by the Federal Share of Program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center. The authors report no conflicts of interest in conducting the research. NR 41 TC 7 Z9 7 U1 3 U2 19 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JAN PY 2015 VL 42 IS 1 BP 196 EP 205 DI 10.1118/1.4903292 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AZ0TJ UT WOS:000347957200019 PM 25563260 ER PT J AU Bernatowicz, K Keall, P Mishra, P Knopf, A Lomax, A Kipritidis, J AF Bernatowicz, K. Keall, P. Mishra, P. Knopf, A. Lomax, A. Kipritidis, J. TI Quantifying the impact of respiratory-gated 4D CT acquisition on thoracic image quality: A digital phantom study SO MEDICAL PHYSICS LA English DT Article DE respiratory-gated 4D CT; beam paused 4D CT; image quality assessment; XCAT phantom ID 4-DIMENSIONAL COMPUTED-TOMOGRAPHY; RADIOTHERAPY PATIENTS; TUMOR MOTION; XCAT PHANTOM; LUNG-CANCER; VENTILATION; SIMULATION; PARAMETERS; ARTIFACTS; PERFUSION AB Purpose: Prospective respiratory-gated 4D CT has been shown to reduce tumor image artifacts by up to 50% compared to conventional 4D CT. However, to date no studies have quantified the impact of gated 4D CT on normal lung tissue imaging, which is important in performing dose calculations based on accurate estimates of lung volume and structure. To determine the impact of gated 4D CT on thoracic image quality, the authors developed a novel simulation framework incorporating a realistic deformable digital phantom driven by patient tumor motion patterns. Based on this framework, the authors test the hypothesis that respiratory-gated 4D CT can significantly reduce lung imaging artifacts. Methods: Our simulation framework synchronizes the 4D extended cardiac torso (XCAT) phantom with tumor motion data in a quasi real-time fashion, allowing simulation of three 4D CT acquisition modes featuring different levels of respiratory feedback: (i) "conventional" 4D CT that uses a constant imaging and couch-shift frequency, (ii) "beam paused" 4D CT that interrupts imaging to avoid oversampling at a given couch position and respiratory phase, and (iii) "respiratory-gated" 4D CT that triggers acquisition only when the respiratory motion fulfills phase-specific displacement gating windows based on prescan breathing data. Our framework generates a set of ground truth comparators, representing the average XCAT anatomy during beam-on for each of ten respiratory phase bins. Based on this framework, the authors simulated conventional, beam-paused, and respiratory-gated 4D CT images using tumor motion patterns from seven lung cancer patients across 13 treatment fractions, with a simulated 5.5 cm(3) spherical lesion. Normal lung tissue image quality was quantified by comparing simulated and ground truth images in terms of overall mean square error (MSE) intensity difference, threshold-based lung volume error, and fractional false positive/false negative rates. Results: Averaged across all simulations and phase bins, respiratory-gating reduced overall thoracic MSE by 46% compared to conventional 4D CT (p similar to 10(-19)). Gating leads to small but significant (p < 0.02) reductions in lung volume errors (1.8%-1.4%), false positives (4.0%-2.6%), and false negatives (2.7%-1.3%). These percentage reductions correspond to gating reducing image artifacts by 24-90 cm(3) of lung tissue. Similar to earlier studies, gating reduced patient image dose by up to 22%, but with scan time increased by up to 135%. Beam paused 4D CT did not significantly impact normal lung tissue image quality, but did yield similar dose reductions as for respiratory-gating, without the added cost in scanning time. Conclusions: For a typical 6 L lung, respiratory-gated 4D CT can reduce image artifacts affecting up to 90 cm(3) of normal lung tissue compared to conventional acquisition. This image improvement could have important implications for dose calculations based on 4D CT. Where image quality is less critical, beam paused 4D CT is a simple strategy to reduce imaging dose without sacrificing acquisition time. (c) 2015 American Association of Physicists in Medicine. C1 [Bernatowicz, K.; Knopf, A.; Lomax, A.] Paul Scherrer Inst, Ctr Proton Therapy, CH-5232 Villigen, Switzerland. [Bernatowicz, K.; Knopf, A.; Lomax, A.] ETH, Dept Phys, CH-8092 Zurich, Switzerland. [Keall, P.; Kipritidis, J.] Univ Sydney, Sydney Med Sch, Radiat Phys Lab, Sydney, NSW 2006, Australia. [Mishra, P.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Mishra, P.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kipritidis, J (reprint author), Univ Sydney, Sydney Med Sch, Radiat Phys Lab, Sydney, NSW 2006, Australia. EM kingab@student.ethz.ch; john.kipritidis@sydney.edu.au FU NHMRC Australia; Cancer Institute NSW; Swiss National Fund (SNF) [320030_143942/1] FX The authors acknowledge the financial support of an NHMRC Australia Fellowship, Cancer Institute NSW Early Career Fellowship, and Swiss National Fund (SNF 320030_143942/1). Thanks to Yelin Suh for clarifying some questions on the Cyberknife Synchrony database. The authors want to state that no actual or potential conflicts of interest exist. NR 31 TC 3 Z9 3 U1 0 U2 5 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JAN PY 2015 VL 42 IS 1 BP 324 EP 334 DI 10.1118/1.4903936 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AZ0TJ UT WOS:000347957200031 PM 25563272 ER PT J AU Kopacz, MS McCarten, JM Vance, CG Connery, AL AF Kopacz, Marek S. McCarten, Janet M. Vance, C. Garland Connery, April L. TI A Preliminary Study for Exploring Different Sources of Guilt in a Sample of Veterans Who Sought Chaplaincy Services SO MILITARY PSYCHOLOGY LA English DT Article DE suicide; veterans; guilt ID POSTTRAUMATIC-STRESS-DISORDER; SUICIDAL IDEATION; COMBAT VETERANS; MOOD DISORDERS; RISK-FACTORS; SHAME; PREVALENCE; CARE; EXPOSURE; PLANS AB Limited research has suggested that experiencing guilt may contribute to the risk of suicidal behavior in some veteran populations. Using data collected by chaplains, this study compared the frequency with which 94 veterans with a history of suicide ideation experienced guilt relative to 670 veterans without a history of ideation. We then compared main sources of guilt reported by ideators and nonideators. Ideators reported experiencing guilt significantly more often than nonideators. No differences were noted for the source of guilt among those who reported frequently experiencing this emotion. Ideators with an infrequent experience of guilt significantly more often named life and the military as the main source of this emotion. Clinicians should be mindful of the need to appropriately assess for and address guilt among veterans at increased risk of suicide. A variety of sources, not limited only to military experiences, may contribute to a veteran's sense of guilt. C1 [Kopacz, Marek S.; McCarten, Janet M.] US Dept Vet Affairs, VISN Ctr Excellence Suicide Prevent 2, Canandaigua, NY 14424 USA. [Vance, C. Garland] US Dept Vet Affairs, Charles George VA Med Ctr, Asheville, NC USA. [Connery, April L.] US Dept Vet Affairs, Canandaigua VA Med Ctr, Canandaigua, NY 14424 USA. RP Kopacz, MS (reprint author), US Dept Vet Affairs, VISN Ctr Excellence Suicide Prevent 2, 400 Ft Hill Ave, Canandaigua, NY 14424 USA. EM marek.kopacz@va.gov NR 39 TC 3 Z9 3 U1 1 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0899-5605 EI 1532-7876 J9 MIL PSYCHOL JI Milit. Psychol. PD JAN PY 2015 VL 27 IS 1 BP 1 EP 8 DI 10.1037/mil0000061 PG 8 WC Psychology, Multidisciplinary SC Psychology GA AZ0DX UT WOS:000347917500001 ER PT J AU Lennerz, BS Vafai, SB Delaney, NF Clish, CB Deik, AA Pierce, KA Ludwig, DS Mootha, VK AF Lennerz, Belinda S. Vafai, Scott B. Delaney, Nigel F. Clish, Clary B. Deik, Amy A. Pierce, Kerry A. Ludwig, David S. Mootha, Vamsi K. TI Effects of sodium benzoate, a widely used food preservative, on glucose homeostasis and metabolic profiles in humans SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Benzoate; Diabetes; Hippurate; Preservative; Tryptophan ID ACIDS; CHALLENGE; INSULIN AB Sodium benzoate is a widely used preservative found in many foods and soft drinks. It is metabolized within mitochondria to produce hippurate, which is then cleared by the kidneys. We previously reported that ingestion of sodium benzoate at the generally regarded as safe (GRAS) dose leads to a robust excursion in the plasma hippurate level [1]. Since previous reports demonstrated adverse effects of benzoate and hippurate on glucose homeostasis in cells and in animal models, we hypothesized that benzoate might represent a widespread and underappreciated diabetogenic dietary exposure in humans. Here, we evaluated whether acute exposure to GRAS levels of sodium benzoate alters insulin and glucose homeostasis through a randomized, controlled, cross-over study of 14 overweight subjects. Serial blood samples were collected following an oral glucose challenge, in the presence or absence of sodium benzoate. Outcome measurements included glucose, insulin, glucagon, as well as temporal mass spectrometry-based metabolic profiles. We did not find a statistically significant effect of an acute oral exposure to sodium benzoate on glucose homeostasis. Of the 146 metabolites targeted, four changed significantly in response to benzoate, including the expected rise in benzoate and hippurate. In addition, anthranilic acid, a tryptophan metabolite, exhibited a robust rise, while acetylglycine dropped. Although our study shows that GRAS doses of benzoate do not have an acute, adverse effect on glucose homeostasis, future studies will be necessary to explore the metabolic impact of chronic benzoate exposure. (C) 2014 Elsevier Inc. All rights reserved. C1 [Lennerz, Belinda S.; Ludwig, David S.] Boston Childrens Hosp, Boston, MA 02115 USA. [Vafai, Scott B.; Delaney, Nigel F.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Vafai, Scott B.; Delaney, Nigel F.; Clish, Clary B.; Deik, Amy A.; Pierce, Kerry A.; Mootha, Vamsi K.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. RP Mootha, VK (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM belinda.lennerz@childrens.harvard.edu; vafai@molbio.mgh.harvard.edu; nigel.delaney@post.harvard.edu; clary@broadinstitute.org; adeik@broadinstitute.org; kpierce@broadinstitute.org; david.ludwig@childrens.harvard.edu; vamsi@hms.harvard.edu FU Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Research Resources, National Institutes of Health) [UL1 TR001102, UL1 RR025758]; Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [UL1 TR001102, UL1 RR025758]; Harvard University and its affiliated academic health care centers; Translational Research Program at Boston Children's Hospital [70096]; National Institute of Diabetes and Digestive and Kidney Diseases [K24DK082730]; New Balance Foundation; National Institutes of Health [R01DK081457] FX This work was supported by grants from the 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 UL1 TR001102, UL1 RR025758), financial contributions from Harvard University and its affiliated academic health care centers, as well as the Translational Research Program at Boston Children's Hospital (Grant # 70096). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, the National Center for Research Resources, or the National Institutes of Health. DSL is supported by a mid-career mentoring award (grant # K24DK082730) from the National Institute of Diabetes and Digestive and Kidney Diseases, and the New Balance Foundation. VKM is an Investigator of the Howard Hughes Medical Institute and is also supported by a grant from the National Institutes of Health (R01DK081457). We thank Dr. Henry Feldman for assistance with statistics, Dr. Rocco Anzaldi for beverage formulation, and Dr. Anupam Patigri for assistance with figure art. NR 19 TC 4 Z9 4 U1 4 U2 22 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JAN PY 2015 VL 114 IS 1 BP 73 EP 79 DI 10.1016/j.ymgme.2014.11.010 PG 7 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA AZ4GD UT WOS:000348178900013 PM 25497115 ER PT J AU Ligibel, JA Alfano, CM Courneya, KS Demark-Wahnefried, W Burger, RA Chlebowski, RT Fabian, CJ Gucalp, A Hershman, DL Hudson, MM Jones, LW Kakarala, M Ness, KK Merrill, JK Wollins, DS Hudis, CA AF Ligibel, Jennifer A. Alfano, Catherine M. Courneya, Kerry S. Demark-Wahnefried, Wendy Burger, Robert A. Chlebowski, Rowan T. Fabian, Carol J. Gucalp, Ayca Hershman, Dawn L. Hudson, Melissa M. Jones, Lee W. Kakarala, Madhuri Ness, Kirsten K. Merrill, Janette K. Wollins, Dana S. Hudis, Clifford A. TI American Society of Clinical Oncology Position Statement on Obesity and Cancer EDITORIAL COMMENT SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material C1 [Ligibel, Jennifer A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Alfano, Catherine M.] NCI, Bethesda, MD 20892 USA. [Courneya, Kerry S.] Univ Alberta, Edmonton, AB, Canada. [Demark-Wahnefried, Wendy] Univ Alabama Birmingham, Birmingham, AL USA. [Burger, Robert A.] Univ Penn, Philadelphia, PA 19104 USA. [Chlebowski, Rowan T.] Harbor Univ Calif Los Angeles Med Ctr, Torrance, CA USA. [Fabian, Carol J.] Univ Kansas, Med Ctr, Westwood, KS USA. [Gucalp, Ayca; Jones, Lee W.; Hudis, Clifford A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Hershman, Dawn L.] Columbia Univ, Med Ctr, New York, NY USA. [Hudson, Melissa M.; Ness, Kirsten K.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Kakarala, Madhuri] Van Andel Inst, Grand Rapids, MI USA. [Merrill, Janette K.; Wollins, Dana S.] Amer Soc Clin Oncol, Alexandria, VA USA. RP Ligibel, JA (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7828 EI 1533-9866 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD JAN PY 2015 VL 70 IS 1 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AZ3QI UT WOS:000348141400015 ER PT J AU Ginat, DT Freitag, SK AF Ginat, Daniel Thomas Freitag, Suzanne K. TI Orbital Emphysema Complicating Jones Tube Placement in a Patient Treated With Continuous Positive Airway Pressure SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Editorial Material C1 [Ginat, Daniel Thomas] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [Freitag, Suzanne K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Ginat, DT (reprint author), Univ Chicago, Dept Radiol, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM ginatd01@gmail.com NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0740-9303 EI 1537-2677 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD JAN-FEB PY 2015 VL 31 IS 1 BP E25 EP E25 DI 10.1097/IOP.0000000000000299 PG 1 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA AY7YP UT WOS:000347772000012 PM 25275788 ER PT J AU Schoenleber, M Sippel, LM Jakupcak, M Tull, MT AF Schoenleber, Michelle Sippel, Lauren M. Jakupcak, Matthew Tull, Matthew T. TI Role of Trait Shame in the Association Between Posttraumatic Stress and Aggression Among Men With a History of Interpersonal Trauma SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE posttraumatic stress; shame; guilt; aggression; interpersonal violence ID INTIMATE PARTNER VIOLENCE; COGNITIVE-PROCESSING THERAPY; EXPERIENTIAL AVOIDANCE; MILITARY VETERANS; DISORDER SYMPTOMS; PSYCHOMETRIC PROPERTIES; GUILT; PTSD; PERPETRATION; VICTIMS AB Given the theoretical and empirical associations among posttraumatic stress, shame, and interpersonal aggression, this study examined whether trait shame accounts for the associations between posttraumatic stress and aggressive behavior in a sample of 103 men with a history of interpersonal trauma. Results indicated that trait shame accounted for the associations of posttraumatic stress with the variety of both physically and psychologically aggressive behavior, as well as with the frequency of physical aggression. This study also examined trait guilt, given its conceptual relationship to both shame and posttraumatic stress; unlike trait shame, trait guilt did not account for the association between posttraumatic stress and the variety of physically aggressive acts. Additionally, although trait guilt reduced the association between posttraumatic stress and the frequency of physical aggression, the indirect path including guilt was nonsignificant. Taken together, the present study supports existing theories suggesting that shame, but not guilt, may contribute to aggressive behavior, especially among individuals with histories of traumatic exposure. C1 [Schoenleber, Michelle; Sippel, Lauren M.; Tull, Matthew T.] Univ Mississippi, Med Ctr, Dept Psychiat & Human Behav, Jackson, MS 39216 USA. [Jakupcak, Matthew] VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA USA. [Jakupcak, Matthew] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Schoenleber, M (reprint author), Univ Mississippi, Med Ctr, Div Psychol, Dept Psychiat & Human Behav, 2500 N State St, Jackson, MS 39216 USA. EM mschoenleber@umc.edu NR 61 TC 3 Z9 3 U1 6 U2 15 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 EI 1942-969X J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD JAN PY 2015 VL 7 IS 1 BP 43 EP 49 DI 10.1037/a0037434 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AZ3BA UT WOS:000348101500007 PM 25793592 ER PT J AU Hoerster, KD Jakupcak, M Stephenson, KR Fickel, JJ Simons, CE Hedeen, A Dwight-Johnson, M Whealin, JM Chaney, E Felker, BL AF Hoerster, Katherine D. Jakupcak, Matthew Stephenson, Kyle R. Fickel, Jacqueline J. Simons, Carol E. Hedeen, Ashley Dwight-Johnson, Megan Whealin, Julia M. Chaney, Edmund Felker, Bradford L. TI A Pilot Trial of Telephone-Based Collaborative Care Management for PTSD Among Iraq/Afghanistan War Veterans SO TELEMEDICINE AND E-HEALTH LA English DT Article DE primary care mental health; posttraumatic stress disorder; veterans; collaborative care ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH DIAGNOSES; RANDOMIZED CONTROLLED-TRIAL; AFGHANISTAN VETERANS; ANXIETY DISORDERS; DEPRESSION; SERVICES; IRAQ; PSYCHOTHERAPY; SYMPTOMS AB Background: Collaborative care and care management are cornerstones of Primary Care-Mental Health Integration (PC-MHI) and have been shown to reduce depressive symptoms. Historically, the standard of Veterans Affairs (VA) collaborative care was referring patients with posttraumatic stress disorder (PTSD) to specialty care. Although referral to evidence-based specialty care is ideal, many veterans with PTSD do not receive such care. To address this issue and reduce barriers to care, VA currently recommends veterans with PTSD be offered treatment within PC-MHI as an alternative. The current project outlines a pilot implementation of an established telephone-based collaborative care model-Translating Initiatives for Depression into Effective Solutions (TIDES)-adapted for Iraq/Afghanistan War veterans with PTSD symptoms (TIDES/PTSD) seen in a postdeployment primary care clinic. Materials and Methods: Structured medical record extraction and qualitative data collection procedures were used to evaluate acceptability, feasibility, and outcomes. Results: Most participants (n=17) were male (94.1%) and white (70.6%). Average age was 31.2 (standard deviation=6.4) years. TIDES/PTSD was successfully implemented within PC-MHI and was acceptable to patients and staff. Additionally, the total number of care manager calls was positively correlated with number of psychiatry visits (r=0.63, p<0.05) and amount of reduction in PTSD symptoms (r=0.66, p<0.05). Overall, participants in the pilot reported a significant reduction in PTSD symptoms over the course of the treatment (t=2.87, p=0.01). Conclusions: TIDES can be successfully adapted and implemented for use among Iraq/Afghanistan veterans with PTSD. Further work is needed to test the effectiveness and implementation of this model in other sites and among veterans of other eras. C1 [Hoerster, Katherine D.; Jakupcak, Matthew; Stephenson, Kyle R.; Felker, Bradford L.] VA Puget Sound Healthcare Syst, Seattle Div, Mental Hlth Serv, Seattle, WA 98108 USA. [Hoerster, Katherine D.; Jakupcak, Matthew; Chaney, Edmund; Felker, Bradford L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Stephenson, Kyle R.] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA. [Fickel, Jacqueline J.; Dwight-Johnson, Megan] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Simons, Carol E.; Hedeen, Ashley; Chaney, Edmund] VA Puget Sound Healthcare Syst, Seattle Div, Res & Dev Serv, Seattle, WA USA. [Whealin, Julia M.] Natl Ctr PTSD, Pacific Isl Div, Honolulu, HI USA. [Whealin, Julia M.] Natl Ctr PTSD, VA Pacific Isl Healthcare Syst, Honolulu, HI USA. [Whealin, Julia M.] Univ Hawaii, Sch Med, Dept Psychiat, Honolulu, HI 96822 USA. RP Hoerster, KD (reprint author), VA Puget Sound Healthcare Syst, Seattle Div, Mental Hlth Serv, 1660 South Columbian Way S-116, Seattle, WA 98108 USA. EM Katherine.Hoerster@va.gov FU Office of Research and Development, U.S. Department of Veterans Affairs [SHP08-184] FX This material is based on work supported by the Office of Research and Development, U.S. Department of Veterans Affairs (grant SHP08-184). NR 29 TC 2 Z9 2 U1 1 U2 6 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 EI 1556-3669 J9 TELEMED E-HEALTH JI Telemed. e-Health PD JAN 1 PY 2015 VL 21 IS 1 BP 42 EP 47 DI 10.1089/tmj.2013.0337 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AZ6BI UT WOS:000348302800007 PM 25405394 ER PT J AU Maguire, LH Song, MY Strate, LL Giovannucci, EL Chan, AT AF Maguire, Lillias H. Song, Mingyang Strate, Lisa L. Giovannucci, Edward L. Chan, Andrew T. TI RESIDENT'S FORUM Association of Geographic and Seasonal Variation With Diverticulitis Admissions SO JAMA SURGERY LA English DT Article ID VITAMIN-D STATUS; UNITED-STATES; REDUCED RISK; DISEASE; CANCER; COLON AB IMPORTANCE The incidence of diverticulitis has been associated with geographic and seasonal variation. Low levels of circulating vitamin D are associated with diverticulitis. We investigated the association between UV light and diverticulitis. OBSERVATIONS We identified nonelective diverticulitis admissions in the Nationwide Inpatient Sample and linked hospital locations to UV data. We examined UV exposure in relation to risk of admission for diverticulitis. We identified geographic and seasonal trends among 226 522 nonelective admissions for diverticulitis. Compared with high-UV areas, low-UV areas had a higher rate of diverticulitis (751.8 vs 668.1 per 100 000 admissions; P < .001), diverticular abscess (12.0% vs 9.7%; P < .001), and colectomy (13.5% vs 11.5%; P < .001). We also observed significant seasonal variation, with a lower rate of diverticulitis in the winter (645 per 100 000) compared with the summer (748 per 100 000) (P < .001). The summer increase was more evident in areas with the greatest UV fluctuation vs areas with the least UV fluctuation (120 vs 70 per 100 000; P = .01). CONCLUSIONS AND RELEVANCE Low UV light exposure is associated with an increased rate of diverticulitis admissions and greater seasonal variation. Because UV exposure largely determines vitamin D status, these findings support a role for vitamin D in the pathogenesis of diverticulitis. C1 [Maguire, Lillias H.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Song, Mingyang; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr & Epidemiol, Boston, MA 02115 USA. [Strate, Lisa L.] Univ Washington, Div Gastroenterol, Seattle, WA 98195 USA. [Giovannucci, Edward L.; Chan, Andrew T.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, 55 Fruit St,Gray Jackson 722, Boston, MA 02114 USA. EM achan@partners.org FU American College of Gastroenterology; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, US Department of Health and Human Services [K24 DK 098311] FX This work was supported by a Clinical Research Award from the American College of Gastroenterology (Dr Maguire) and grant K24 DK 098311 from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, US Department of Health and Human Services (Dr Chan). Dr Chan is a Damon Runyon Clinical Investigator. NR 23 TC 7 Z9 7 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD JAN PY 2015 VL 150 IS 1 BP 74 EP 77 DI 10.1001/jamasurg.2014.2049 PG 4 WC Surgery SC Surgery GA AZ5AO UT WOS:000348232900015 PM 25409019 ER PT J AU Ataer-Cansizoglu, E Kalpathy-Cramer, J You, S Keck, K Erdogmus, D Chiang, MF AF Ataer-Cansizoglu, E. Kalpathy-Cramer, J. You, S. Keck, K. Erdogmus, D. Chiang, M. F. TI Analysis of Underlying Causes of Inter-expert Disagreement in Retinopathy of Prematurity Diagnosis Application of Machine Learning Principles SO METHODS OF INFORMATION IN MEDICINE LA English DT Article DE Inter-expert disagreement; feature selection; retinopathy of prematurity; kernel density estimation ID PLUS DISEASE DIAGNOSIS; MUTUAL INFORMATION; IMAGE-ANALYSIS; AGREEMENT; CRYOTHERAPY; TORTUOSITY AB Objective: Inter-expert variability in image-based clinical diagnosis has been demonstrated in many diseases including retinopathy of prematurity (ROP), which is a disease affecting low birth weight infants and is a major cause of childhood blindness. In order to better understand the underlying causes of variability among experts, we propose a method to quantify the variability of expert decisions and analyze the relationship between expert diagnoses and features computed from the images. Identification of these features is relevant for development of computer-based decision support systems and educational systems in ROP, and these methods may be applicable to other diseases where inter-expert variability is observed. Methods: The experiments were carried out on a dataset of 34 retinal images, each with diagnoses provided independently by 22 experts. Analysis was performed using concepts of Mutual Information (MI) and Kernel Density Estimation. A large set of structural features (a total of 66) were extracted from retinal images. Feature selection was utilized to identify the most important features that correlated to actual clinical decisions by the 22 study experts. The best three features for each observer were selected by an exhaustive search on all possible feature subsets and considering joint MI as a relevance criterion. We also compared our results with the results of Cohen's Kappa [36] as an inter-rater reliability measure. Results: The results demonstrate that a group of observers (17 among 22) decide consistently with each other. Mean and second central moment of arteriolar tortuosity is among the reasons of disagreement between this group and the rest of the observers, meaning that the group of experts consider amount of tortuosity as well as the variation of tortuosity in the image. Conclusion: Given a set of image-based features, the proposed analysis method can identify critical image-based features that lead to expert agreement and disagreement in diagnosis of ROP. Although tree-based features and various statistics such as central moment are not popular in the literature, our results suggest that they are important for diagnosis. C1 [Ataer-Cansizoglu, E.; You, S.; Erdogmus, D.] Northeastern Univ, Cognit Syst Lab, Boston, MA 02115 USA. [Kalpathy-Cramer, J.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Keck, K.; Chiang, M. F.] Oregon Hlth & Sci Univ, Dept Ophthalmol & Med Informat & Clin Epidemiol, Portland, OR 97201 USA. RP Ataer-Cansizoglu, E (reprint author), Northeastern Univ, Dept Elect & Comp Engn, 409 Dana Res Ctr 360 Huntington Ave, Boston, MA 02115 USA. EM ataer@ece.neu.edu OI Kalpathy-Cramer, Jayashree/0000-0001-8906-9618 FU NIH [EY19474, 8P41GM103545-14]; NLM [4R00LM009889]; Research to Prevent Blindness FX This work is supported by grants NIH EY19474, NLM 4R00LM009889 and NIH 8P41GM103545-14. MFC also acknowledges unrestricted departmental funding from Research to Prevent Blindness. NR 37 TC 3 Z9 3 U1 1 U2 2 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PY 2015 VL 54 IS 1 BP 93 EP 102 DI 10.3414/ME13-01-0081 PG 10 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA AY9KH UT WOS:000347868300013 PM 25434784 ER PT J AU Shah, AA Seiffert-Sinha, K Sirois, D Werth, VP Rengarajan, B Zrnchik, W Attwood, K Sinha, AA AF Shah, Amit Aakash Seiffert-Sinha, Kristina Sirois, David Werth, Victoria P. Rengarajan, Badri Zrnchik, William Attwood, Kristopher Sinha, Animesh A. TI Development of a Disease Registry for Autoimmune Bullous Diseases: Initial Analysis of the Pemphigus Vulgaris Subset SO ACTA DERMATO-VENEREOLOGICA LA English DT Article DE autoimmune bullous disease; disease registry; epidemiology; pemphigus vulgaris ID GENDER-DIFFERENCES; EPIDEMIOLOGY; POPULATION; RISK AB Pemphigus vulgaris (PV) is a rare, potentially life threatening, autoimmune blistering skin disease. The International Pemphigus and Pemphigoid Foundation (IPPF) has recently developed a disease registry with the aim to enhance our understanding of autoimmune bulbous diseases with the long-term goal of acquiring information to improve patient care. Patients were recruited to the IPPF disease registry through direct mail, e-mail, advertisements, and articles in the IPPF-quarterly, -website, -Facebook webpage, and IPPF Peer Health Coaches to complete a 38-question survey. We present here the initial analysis of detailed clinical information collected on 393 PV patients. We report previously unrecognized gender differences in terms of lesion location, autoimmune comorbidity, and delay in diagnosis. The IPPF disease registry serves as a useful resource and guide for future clinical investigation. C1 [Shah, Amit Aakash; Seiffert-Sinha, Kristina; Sinha, Animesh A.] SUNY Buffalo, Dept Dermatol, Buffalo, NY 14203 USA. [Sirois, David] NYU, Coll Dent, Dept Oral Med, New York, NY USA. [Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Werth, Victoria P.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Rengarajan, Badri] Archimedes Inc, San Francisco, CA USA. [Zrnchik, William] Int Pemphigus & Pemphigoid Fdn, Sacramento, CA USA. [Attwood, Kristopher] Roswell Pk Canc Inst, Dept Biostat & Bioinformat, Buffalo, NY 14263 USA. RP Sinha, AA (reprint author), SUNY Buffalo, Dept Dermatol, Clin & Translat Res Ctr, Room 6078,875 Ellicott St, Buffalo, NY 14203 USA. EM aasinha@buffalo.edu NR 31 TC 2 Z9 2 U1 0 U2 0 PU ACTA DERMATO-VENEREOLOGICA PI UPPSALA PA TRADGARDSGATAN 14, UPPSALA, SE-753 09, SWEDEN SN 0001-5555 EI 1651-2057 J9 ACTA DERM-VENEREOL JI Acta Derm.-Venereol. PY 2015 VL 95 IS 1 BP 86 EP 90 DI 10.2340/00015555-1854 PG 5 WC Dermatology SC Dermatology GA AY7TR UT WOS:000347762200017 PM 24691863 ER PT J AU Zaky, A Zeliadt, SB Treggiari, MM AF Zaky, A. Zeliadt, S. B. Treggiari, M. M. TI Patient-level interventions to prevent the acquisition of resistant Gram-negative bacteria in critically ill patients: a systematic review SO ANAESTHESIA AND INTENSIVE CARE LA English DT Review DE decontamination; Gram-negative bacterial infections; infection control; intensive care units ID INTENSIVE-CARE-UNIT; VENTILATOR-ASSOCIATED PNEUMONIA; PLACEBO-CONTROLLED TRIAL; SEVERE ACUTE-PANCREATITIS; DIGESTIVE-TRACT; DOUBLE-BLIND; SELECTIVE DECONTAMINATION; ANTIMICROBIAL RESISTANCE; PROBIOTIC PROPHYLAXIS; DISEASES SOCIETY AB The rising incidence of multidrug-resistant Gram-negative bacterial (MDR-GNB) infections acquired in intensive care units has prompted a variety of patient-level infection control efforts. However, it is not known whether these measures are effective in reducing colonisation and infection. The purpose of this systematic review was to assess the efficacy of patient-level interventions for the prevention of colonisation with MDR-GNB and whether these interventions are associated with a reduction in the rate of infection due to MDR-GNB in the intensive care unit. Searches were conducted on Pub Med, Cochrane, EMBASE and World of Science databases to identify comparative interventional studies on patient-level interventions implemented in the intensive care unit. Literature published in English, Spanish or French from January 1, 2000, until April 30, 2013, was searched. A total of 631 reports were found and we included and analysed 13 comparative studies that reported outcomes for an intervention compared with a control group. There were ten randomised and three observational interventional trials evaluating seven interventions. Overall, there was a reduction in colonisation (odds ratio [OR] 0.75; 95% confidence interval [CI] 0.66 to 0.85) and infection (OR 0.66; 95% CI 0.59 to 0.75) with MDR-GNB. This trend persisted after restricting pooled analysis to randomised controlled trials (pooled OR 0.66; 95% CI 0.57 to 0.76 and pooled OR 0.62; 95% Cl 0.54 to 0.72, respectively). We identified a significant reduction in MDR-GNB colonisation and infection through the use of patient-level interventions. This effect was mostly accounted for by selective digestive decontamination. However, given the limitations of the analysed trials, adequately powered controlled studies are needed to further explore the effects of patient-level interventions on colonisation and infection with MDR-GNB. C1 [Zaky, A.; Zeliadt, S. B.] Univ Washington, Dept Hlth Serv, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Treggiari, M. M.] Univ Washington, Dept Epidemiol, Dept Anaesthesiol, Seattle, WA 98195 USA. RP Zaky, A (reprint author), Univ Washington, Dept Hlth Serv, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. EM azaky@uab.edu NR 37 TC 0 Z9 0 U1 0 U2 1 PU AUSTRALIAN SOC ANAESTHETISTS PI EDGECLIFF PA P O BOX 600, EDGECLIFF, NSW 2027, AUSTRALIA SN 0310-057X EI 1448-0271 J9 ANAESTH INTENS CARE JI Anaesth. Intensive Care PD JAN PY 2015 VL 43 IS 1 BP 23 EP 33 PG 11 WC Anesthesiology; Critical Care Medicine SC Anesthesiology; General & Internal Medicine GA AY7TZ UT WOS:000347762900005 PM 25579286 ER PT J AU King, VJ Fontaine, PL Atwood, LA Powers, E Leeman, L Ecker, JL Avery, MD Sakala, C Campos-Outcalt, D Jeffcott-Pera, M Schoof, B AF King, Valerie J. Fontaine, Patricia L. Atwood, Lesley A. Powers, Elizabeth Leeman, Lawrence Ecker, Jeffrey L. Avery, Melissa D. Sakala, Carol Campos-Outcalt, Doug Jeffcott-Pera, Michelle Schoof, Bellinda TI Clinical Practice Guideline Executive Summary: Labor After Cesarean/Planned Vaginal Birth After Cesarean SO ANNALS OF FAMILY MEDICINE LA English DT Editorial Material DE vaginal birth after Cesarean; Cesarean section; VBAC C1 [King, Valerie J.] Oregon Hlth & Sci Univ, Dept Family Med, Portland, OR 97201 USA. [Fontaine, Patricia L.] HealthPartners Inst Educ & Res, Bloomington, MN USA. [Atwood, Lesley A.] Univ Minnesota, Dept Family Med, Hastings, MN USA. [Powers, Elizabeth] Winding Waters Clin PC, Enterprise, OR USA. [Leeman, Lawrence] Univ New Mexico, Sch Med, Albuquerque, NM 87131 USA. [Ecker, Jeffrey L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. [Avery, Melissa D.] Univ Minnesota, Sch Nursing, Hastings, MN USA. [Sakala, Carol] Childbirth Connect, New York, NY USA. [Campos-Outcalt, Doug] Mercy Care Plan, Phoenix, AZ USA. [Jeffcott-Pera, Michelle; Schoof, Bellinda] Amer Acad Family Phys, Leawood, KS 66211 USA. RP Schoof, B (reprint author), Amer Acad Family Phys, 11400 Tomahawk Creek Pkwy, Leawood, KS 66211 USA. EM bschoof@aafp.org NR 0 TC 2 Z9 3 U1 1 U2 4 PU ANNALS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, LEAWOOD, KS 66211-2672 USA SN 1544-1709 EI 1544-1717 J9 ANN FAM MED JI Ann. Fam. Med. PD JAN-FEB PY 2015 VL 13 IS 1 BP 80 EP 81 DI 10.1370/afm.1738 PG 2 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA AZ0JJ UT WOS:000347931600016 PM 25583896 ER PT J AU Sun, Z Prat, A Cheang, MCU Gelber, RD Perou, CM AF Sun, Z. Prat, A. Cheang, M. C. U. Gelber, R. D. Perou, C. M. TI Chemotherapy benefit for 'ER-positive' breast cancer and contamination of Nonluminal subtypes-waiting for TAILORx and RxPONDER SO ANNALS OF ONCOLOGY LA English DT Article DE basal-like; ER-positive; Her2-enriched; luminal A; luminal B; PAM50; OncotypeDX Recurrence Score ID GENE-EXPRESSION; MOLECULAR PORTRAITS; MONOCLONAL-ANTIBODY; DISTANT RECURRENCE; ESTROGEN-RECEPTOR; ENDOCRINE THERAPY; PAM50 RISK; WOMEN; SURVIVAL; MODELS AB Retrospective analyses of NSABP B20 and SWOG 8814 showed a large benefit of chemotherapy in patients with ER-positive tumors and high OncotypeDX Recurrence Score (RSa parts per thousand yen31). However, it might be possible that both studies may be contaminated by non-luminal tumors, especially in high-risk RS group. We conducted simulations in order to obtain a better understanding of how the NSABP B20 and SWOG 8814 results would have been if non-luminal breast cancer would have been excluded. Simulations were done separately for the node-negative and node-positive cohorts. The results of the simulations suggest that the non-luminal tumors are augmenting the apparent benefit of chemotherapy, but do not appear to be responsible for the entire effect. These simulations could provide information about the potential influence of contamination by unexpected tumor subtypes on the future results of TAILORx and RxPONDER clinical trials. C1 [Sun, Z.; Gelber, R. D.] Dana Farber Canc Inst, IBCSG Stat Ctr, Boston, MA 02115 USA. [Sun, Z.; Gelber, R. D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Prat, A.] Vall DHebron Inst Oncol VHIO, Translat Genom Grp, Barcelona, Spain. [Prat, A.] Hosp Clin Barcelona, Dept Med Oncol, Barcelona, Spain. [Perou, C. M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Gelber, RD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, IBCSG Stat Ctr, Boston, MA 02115 USA. EM gelber@jimmy.harvard.edu; chuck_perou@med.unc.edu RI Prat, Aleix/P-8561-2014; OI Prat, Aleix/0000-0003-2377-540X; Perou, Charles/0000-0001-9827-2247 NR 26 TC 2 Z9 2 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JAN PY 2015 VL 26 IS 1 BP 70 EP 74 DI 10.1093/annonc/mdu493 PG 5 WC Oncology SC Oncology GA AY2JP UT WOS:000347416300011 PM 25355719 ER PT J AU Krop, IE Lin, NU Blackwell, K Guardino, E Huober, J Lu, M Miles, D Samant, M Welslau, M Dieras, V AF Krop, I. E. Lin, N. U. Blackwell, K. Guardino, E. Huober, J. Lu, M. Miles, D. Samant, M. Welslau, M. Dieras, V. TI Trastuzumab emtansine (T-DM1) versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer and central nervous system metastases: a retrospective, exploratory analysis in EMILIA SO ANNALS OF ONCOLOGY LA English DT Article DE ado-trastuzumab emtansine; T-DM1; metastatic breast cancer; central nervous system metastasis ID WHOLE-BRAIN RADIOTHERAPY; EXTRACRANIAL DISEASE; CNS METASTASES; SURVIVAL; OUTCOMES; ERA; RADIOSURGERY; THERAPY; TRIAL AB We characterized the incidence of central nervous system (CNS) metastases after treatment with trastuzumab emtansine (T-DM1) versus capecitabine-lapatinib (XL), and treatment efficacy among patients with pre-existing CNS metastases in the phase III EMILIA study. In EMILIA, patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer previously treated with trastuzumab and a taxane were randomized to T-DM1 or XL until disease progression. Patients with treated, asymptomatic CNS metastases at baseline and patients developing postbaseline CNS metastases were identified retrospectively by independent review; exploratory analyses were carried out. Among 991 randomized patients (T-DM1 = 495; XL = 496), 95 (T-DM1 = 45; XL = 50) had CNS metastases at baseline. CNS progression occurred in 9 of 450 (2.0%) and 3 of 446 (0.7%) patients without CNS metastases at baseline in the T-DM1 and XL arms, respectively, and in 10 of 45 (22.2%) and 8 of 50 (16.0%) patients with CNS metastases at baseline. Among patients with CNS metastases at baseline, a significant improvement in overall survival (OS) was observed in the T-DM1 arm compared with the XL arm [hazard ratio (HR) = 0.38; P = 0.008; median, 26.8 versus 12.9 months]. Progression-free survival by independent review was similar in the two treatment arms (HR = 1.00; P = 1.000; median, 5.9 versus 5.7 months). Multivariate analyses demonstrated similar results. Grade a parts per thousand yen3 adverse events were reported in 48.8% and 63.3% of patients with CNS metastases at baseline administered T-DM1 and XL, respectively; no new safety signals were observed. In this retrospective, exploratory analysis, the rate of CNS progression in patients with HER2-positive advanced breast cancer was similar for T-DM1 and for XL, and higher overall in patients with CNS metastases at baseline compared with those without CNS metastases at baseline. In patients with treated, asymptomatic CNS metastases at baseline, T-DM1 was associated with significantly improved OS compared with XL. C1 [Krop, I. E.; Lin, N. U.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Blackwell, K.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Guardino, E.; Lu, M.] Genentech Inc, Oncol, Prod Dev, San Francisco, CA 94080 USA. [Huober, J.] Cantonal Hosp, Dept Med Oncol, St Gallen, Switzerland. [Huober, J.] Cantonal Hosp, Breast Ctr, St Gallen, Switzerland. [Miles, D.] Mt Vernon Canc Ctr, Dept Med Oncol, Northwood, Middx, England. [Samant, M.] Genentech Inc, Biostat, San Francisco, CA 94080 USA. [Welslau, M.] Med Off, Aschaffenburg, Germany. [Dieras, V.] Inst Curie, Dept Med Oncol, Paris, France. RP Krop, IE (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Breast Oncol Ctr,Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM ikrop@partners.org FU Genentech, Inc. FX This work was supported by Genentech, Inc., a member of the Roche Group. The protocol was designed in collaboration with the steering committee by the sponsor. The sponsor managed the data and carried out statistical analyses. The authors had access to all data and were involved in data analysis and interpretation, manuscript writing, and final manuscript approval. The sponsor also reviewed the manuscript. NR 32 TC 38 Z9 40 U1 2 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JAN PY 2015 VL 26 IS 1 BP 113 EP 119 DI 10.1093/annonc/mdu486 PG 7 WC Oncology SC Oncology GA AY2JP UT WOS:000347416300017 PM 25355722 ER PT J AU Niesten, MEF Stieger, C Lee, DJ Merchant, JP Grolman, W Rosowski, JJ Nakajima, HH AF Niesten, Marlien E. F. Stieger, Christof Lee, Daniel J. Merchant, Julie P. Grolman, Wilko Rosowski, John J. Nakajima, Hideko Heidi TI Assessment of the Effects of Superior Canal Dehiscence Location and Size on Intracochlear Sound Pressures SO AUDIOLOGY AND NEURO-OTOLOGY LA English DT Article DE Superior semicircular canal dehiscence; Cochlear pressure; Scala vestibule; Scala tympani; Differential pressure ID CONDUCTIVE HEARING-LOSS; INNER-EAR MECHANICS; MIDDLE-EAR; VERTIGO AB Superior canal dehiscence (SCD) is a defect in the bony covering of the superior semicircular canal. Patients with SCD present with a wide range of symptoms, including hearing loss, yet it is unknown whether hearing is affected by parameters such as the location of the SCD. Our previous human cadaveric temporal bone study, utilizing intracochlear pressure measurements, generally showed that an increase in dehiscence size caused a low-frequency monotonic decrease in the cochlear drive across the partition, consistent with increased hearing loss. This previous study was limited to SCD sizes including and smaller than 2 mm long and 0.7 mm wide. However, the effects of larger SCDs (>2 mm long) were not studied, although larger SCDs are seen in many patients. Therefore, to answer the effect of parameters that have not been studied, this present study assessed the effect of SCD location and the effect of large-sized SCDs (>2 mm long) on intracochlear pressures. We used simultaneous measurements of sound pressures in the scala vestibuli and scala tympani at the base of the cochlea to determine the sound pressure difference across the cochlear partition - a measure of the cochlear drive in a temporal bone preparation - allowing for assessment of hearing loss. We measured the cochlear drive before and after SCDs were made at different locations (e.g. closer to the ampulla of the superior semicircular canal or closer to the common crus) and for different dehiscence sizes (including larger than 2 mm long and 0.7 mm wide). Our measurements suggest the following: (1) different SCD locations result in similar cochlear drive and (2) larger SCDs produce larger decreases in cochlear drive at low frequencies. However, the effect of SCD size seems to saturate as the size increases above 2-3 mm long and 0.7 mm wide. Although the monotonic effect was generally consistent across ears, the quantitative amount of change in cochlear drive due to dehiscence size varied across ears. Additionally, the size of the dehiscence above which the effect on hearing saturated varied across ears. These findings show that the location of the SCD does not generally influence the amount of hearing loss and that SCD size can help explain some of the variability of hearing loss in patients. (c) 2014 S. Karger AG, Basel C1 [Niesten, Marlien E. F.; Grolman, Wilko] Univ Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, Utrecht, Netherlands. [Niesten, Marlien E. F.; Grolman, Wilko] Rudolf Magnus Inst Neurosci, NL-3508 TA Utrecht, Netherlands. [Niesten, Marlien E. F.; Stieger, Christof; Lee, Daniel J.; Merchant, Julie P.; Rosowski, John J.; Nakajima, Hideko Heidi] Harvard Univ, Sch Med, Dept Otol & Laryngol, Eaton Peabody Lab,Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. [Rosowski, John J.; Nakajima, Hideko Heidi] MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. [Stieger, Christof] Univ Bern, Inselspital, ARTORG Ctr, Univ Dept ENT Head & Neck Surg, CH-3010 Bern, Switzerland. RP Nakajima, HH (reprint author), Massachusetts Eye & Ear Infirm, EPL, 243 Charles St, Boston, MA 02114 USA. EM heidi_nakajima@meei.harvard.edu OI Grolman, Wilko/0000-0002-3524-3526 FU NIH/NIDCD [R03DC011158-03] FX This study was funded by the NIH/NIDCD (grant R03DC011158-03). The authors wish to thank Diane Jones, Mike Ravicz and Melissa McKinnon. NR 21 TC 6 Z9 6 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-3030 EI 1421-9700 J9 AUDIOL NEURO-OTOL JI Audiol. Neuro-Otol. PY 2015 VL 20 IS 1 BP 62 EP 71 DI 10.1159/000366512 PG 10 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA AY8FR UT WOS:000347790400006 PM 25531117 ER PT J AU Kim, B Roy, J Shum, WWC Da Silva, N Breton, S AF Kim, Bongki Roy, Jeremy Shum, Winnie W. C. Da Silva, Nicolas Breton, Sylvie TI Role of Testicular Luminal Factors on Basal Cell Elongation and Proliferation in the Mouse Epididymis SO BIOLOGY OF REPRODUCTION LA English DT Article DE androgens; androgen receptor; apoptosis; epididymis; male reproductive tract ID EFFERENT DUCT LIGATION; REGION-SPECIFIC MANNER; RAT EPIDIDYMIS; EPITHELIAL-CELLS; STEM-CELLS; GENE-EXPRESSION; ANDROGEN RECEPTOR; SELF-RENEWAL; IN-VIVO; MICE AB A subset of basal cells (BCs) in the initial segment (IS) of the mouse epididymis has a slender body projection between adjacent epithelial cells. We show here that these projections occasionally cross the apical tight junctions and are in contact with the luminal environment. Luminal testicular factors are critical for the establishment of the IS epithelium, and we investigated their role in the regulation of this luminal sensing property. Efferent duct ligation (EDL) was performed to block luminal flow from the testis without affecting blood flow. Cytokeratin 5 (KRT5) labeling showed a time-dependent reduction of the percentage of BCs with intercellular projections from 1 to 5 days after EDL, compared to controls. Double labeling for caspase-3 and KRT5 showed that a subset of BCs undergoes apoptosis 1 day after EDL. Ki67/KRT5 double labeling showed a low rate of BC proliferation under basal conditions. However, EDL induced a marked increase in the proliferation rate of a subset of BCs 2 days after EDL. A 2-wk treatment with the androgen receptor antagonist flutamide did not affect the number of BCs with intercellular projections, but reduced BC proliferation. Flutamide treatment also reduced the increase in BC proliferation induced 2 days after EDL. We conclude that, in the adult mouse IS, 1) luminal testicular factors play an important role in the ability of BCs to extend their body projection towards the lumen, and are essential for the survival of a subset of BCs; 2) androgens play an important role in the proliferation of some of the BCs that survive the initial insult induced by EDL; and 3) the formation and elongation of BC intercellular projections do not depend on androgens. C1 Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Breton, S (reprint author), Massachusetts Gen Hosp, Simches Res Ctr, Div Nephrol, Program Membrane Biol, CPZN 8204,185 Cambridge St, Boston, MA 02114 USA. EM breton.sylvie@mgh.harvard.edu FU NIH [RO1HD040793, RO1DK097124, RO1HD069623]; Boston Area Diabetes and Endocrinology Research Center [DK57521]; Center for the Study of Inflammatory Bowel Disease [DK43351]; Charles and Ann Sanders Research Scholar Award at MGH FX Supported by NIH grants RO1HD040793 and RO1DK097124 (to S.B.). N.D.S is supported by NIH grant RO1HD069623. The Microscopy Core facility of the MGH Program in Membrane Biology receives support from the Boston Area Diabetes and Endocrinology Research Center (DK57521) and the Center for the Study of Inflammatory Bowel Disease (DK43351). S.B. is a recipient of the Charles and Ann Sanders Research Scholar Award at MGH. NR 61 TC 8 Z9 8 U1 0 U2 4 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 EI 1529-7268 J9 BIOL REPROD JI Biol. Reprod. PD JAN 1 PY 2015 VL 92 IS 1 AR 9 DI 10.1095/biolreprod.114.123943 PG 11 WC Reproductive Biology SC Reproductive Biology GA AZ0DI UT WOS:000347916100009 PM 25411392 ER PT J AU Xiao, YP Freeman, GJ AF Xiao, Yanping Freeman, Gordon J. TI The Microsatellite Instable Subset of Colorectal Cancer Is a Particularly Good Candidate for Checkpoint Blockade Immunotherapy SO CANCER DISCOVERY LA English DT Editorial Material ID BRAF MUTATION; INSTABILITY; FUSOBACTERIUM; CARCINOMA AB The microsatellite instable (MSI) subset of colorectal cancer exhibits an active Th1/CTL immune microenvironment, probably due to recognition of a high number of tumor neoantigens. However, the high expression of checkpoint molecules PD-1, PD-L1, CTLA-4, LAG-3, and IDO in MSI colorectal cancer distinguishes MSI from microsatellite stable colorectal cancer and creates an immunosuppressive microenvironment that may help MSI tumors evade immune destruction by the infiltrating immune cells. Though colorectal cancer does not have a good response rate to PD-1 pathway immunotherapy, these results suggest that the MSI subset of colorectal cancer is a particularly good candidate for checkpoint immunotherapy. (C) 2015 AACR. C1 [Xiao, Yanping; Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Freeman, GJ (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Gordon_Freeman@dfci.harvard.edu FU NIH [P01AI056299, U54CA163125, P50CA101942, HHSN272201100018C] FX This work was supported by NIH grants P01AI056299, U54CA163125, P50CA101942, and HHSN272201100018C (to G.J. Freeman). NR 10 TC 46 Z9 48 U1 2 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD JAN PY 2015 VL 5 IS 1 BP 16 EP 18 DI 10.1158/2159-8290.CD-14-1397 PG 3 WC Oncology SC Oncology GA AY9NK UT WOS:000347877500005 PM 25583798 ER PT J AU van Kruchten, M de Vries, EG Glaudemans, AW van Lanschot, MC van Faassen, M Kema, IP Brown, M Schroder, CP de Vries, EF Hospers, GA AF van Kruchten, Michel de Vries, Elisabeth G. Glaudemans, Andor W. van Lanschot, Meta C. van Faassen, Martijn Kema, Ido P. Brown, Myles Schroder, Carolien P. de Vries, Erik F. Hospers, Geke A. TI Measuring Residual Estrogen Receptor Availability during Fulvestrant Therapy in Patients with Metastatic Breast Cancer SO CANCER DISCOVERY LA English DT Article ID POSTMENOPAUSAL WOMEN; TAMOXIFEN; PET; DIAGNOSIS; TISSUE; TRIAL; MG AB It is unknown whether the current dose of fulvestrant, an estrogen receptor (ER) antagonist, is sufficient for maximal ER downregulation in patients with metastatic breast cancer. We performed a feasibility study to assess ER availability before and during fulvestrant. Sixteen patients with ER-positive metastatic breast cancer underwent positron emission tomography/computed tomography (PET/CT) at baseline (scan 1), day 28 (scan 2), and day 84 (scan 3) to monitor tumor [18 F] fluoroestradiol (FES) uptake. Incomplete reduction in ER availability was predefined as <75% decrease in median tumor FES uptake and a residual standardized uptake value (SUVmax) of >= 1.5. In total, 131 FES-positive lesions were identified (median SUVmax of 2.9; range, 1.7-6.5). The median change in patients during fulvestrant treatment was -85% at scan 2, but varied widely (-99% to +60%). Fulvestrant reduced tumor FES uptake incompletely at scan 2 in 6 (38%) of the 16 patients, which was associated with early progression. SIGNIFICANCE: Serial imaging of tumor estrogen uptake by FES-PET can give insight into the dose needed for ER antagonists to completely abolish ER. FES-PET showed significant residual ER availability in tumors during fulvestrant therapy in 38% of patients, which was associated with early progression. (C)2014 AACR. C1 [van Kruchten, Michel; de Vries, Elisabeth G.; van Lanschot, Meta C.; Hospers, Geke A.] Univ Groningen, Univ Med Ctr Groningen, Dept Med Oncol, NL-9700 AB Groningen, Netherlands. [Glaudemans, Andor W.; de Vries, Erik F.] Univ Groningen, Univ Med Ctr Groningen, Dept Nucl Med & Mol Imaging, NL-9700 AB Groningen, Netherlands. [van Faassen, Martijn; Kema, Ido P.; Schroder, Carolien P.] Univ Groningen, Univ Med Ctr Groningen, Dept Lab Med, NL-9700 AB Groningen, Netherlands. [Brown, Myles] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP de Vries, EF (reprint author), Univ Med Ctr Groningen, Dept Med Oncol, POB 30-001, NL-9700 RB Groningen, Netherlands. EM e.g.e.de.vries@umcg.nl OI Brown, Myles/0000-0002-8213-1658 FU Dutch Cancer Society [RUG 2009-4529]; AstraZeneca FX The research was supported by the Dutch Cancer Society (grant RUG 2009-4529) and a research grant to the UMCG provided by AstraZeneca. NR 30 TC 24 Z9 24 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD JAN PY 2015 VL 5 IS 1 BP 72 EP 81 DI 10.1158/2159-8290.CD-14-0697 PG 10 WC Oncology SC Oncology GA AY9NK UT WOS:000347877500013 PM 25380844 ER PT J AU Zhai, RH Wei, YY Su, L Liu, G Kulke, MH Wain, JC Christiani, DC AF Zhai, Rihong Wei, Yongyue Su, Li Liu, Geoffrey Kulke, Mathew H. Wain, John C. Christiani, David C. TI Whole-miRNome profiling identifies prognostic serum miRNAs in esophageal adenocarcinoma: the influence of Helicobacter pylori infection status SO CARCINOGENESIS LA English DT Article ID SQUAMOUS-CELL CARCINOMA; CIRCULATING MICRORNAS; CANCER-RISK; GASTROESOPHAGEAL JUNCTION; EXPRESSION; BIOMARKERS; ASSOCIATION; DIAGNOSIS; UTILITY; PLASMA AB The present study showed, for the first time, that aberrant cfmiRNAs may contribute to survival outcome of esophageal adenocarcinome (EA) and H. pylori infection status may modify the association between cfmiRNAs and EA survival.Cell free circulating microRNAs (cfmiRNAs) have been recognized as robust and stable biomarkers of cancers. However, little is known about the prognostic significance of cfmiRNAs in esophageal adenocarcinoma (EA). In this study, we explored whether specific cfmiRNA profiles could predict EA prognosis and whether Helicobacter pylori (HP) infection status could influence the association between cfmiRNAs and EA survival outcome. We profiled 1075 miRNAs in pooled serum samples from 30 EA patients and 30 healthy controls. The most relevant cfmiRNAs were then assessed for their associations with EA survival in an independent cohort of 82 patients, using Log-rank test and multivariate Cox regression models. Quantitative real-time PCR (qRT-PCR) was used for cfmiRNA profiling. HP infection status was determined by immunoblotting assay. We identified a panel of 18 cfmiRNAs that could distinguish EA patients from healthy subjects (P = 3.0E-12). In overall analysis and in HP-positive subtype patients, no cfmiRNA was significantly associated with EA prognosis. In HP-negative patients, however, 15 cfmiRNAs were significantly associated with overall survival (OS) (all P < 0.05). A combined 2-cfmiRNA (low miR-3935 and high miR-4286) risk score was constructed; that showed greater risk for worse OS (HR = 2.22, P = 0.0019) than individual cfmiRNA alone. Patients with high-risk score had > 10-fold increased risk of death than patients with low risk score (P = 0.0302; HR = 10.91; P = 0.0094). Our findings suggest that dysregulated cfmiRNAs may contribute to EA survival outcome and HP infection status may modify the association between cfmiRNAs and EA survival. C1 [Zhai, Rihong] Shenzhen Univ, Sch Med, Shenzhen Key Lab Translat Med Tumor, Shenzhen 518060, Peoples R China. [Wei, Yongyue; Su, Li] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Liu, Geoffrey; Christiani, David C.] Princess Margaret Hosp, Dept Med, Toronto, ON M5G 2C4, Canada. [Kulke, Mathew H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wain, John C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Christiani, David C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Zhai, RH (reprint author), Shenzhen Univ, Sch Med, Shenzhen Key Lab Translat Med Tumor, Shenzhen 518060, Peoples R China. EM rzhai@szu.edu.cn; dchris@hsph.harvard.edu RI Liu, Geoffrey/N-4421-2016 FU Harvard-NIEHS Center [ES000002]; National Institute of Health [CA92824, CA74386, CA90578, CA119650] FX Harvard-NIEHS Center (ES000002 to R.Z); National Institute of Health (CA92824, CA74386, CA90578, and CA119650 to D.C.C). NR 40 TC 5 Z9 5 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2015 VL 36 IS 1 BP 87 EP 93 DI 10.1093/carcin/bgu228 PG 7 WC Oncology SC Oncology GA AY9BM UT WOS:000347844700012 PM 25381453 ER PT J AU Chikarmane, SA Tirumani, SH Howard, SA Jagannathan, JP DiPiro, PJ AF Chikarmane, S. A. Tirumani, S. H. Howard, S. A. Jagannathan, J. P. DiPiro, P. J. TI Metastatic patterns of breast cancer subtypes: What radiologists should know in the era of personalized cancer medicine SO CLINICAL RADIOLOGY LA English DT Review ID NERVOUS-SYSTEM METASTASES; DISTANT RECURRENCE; ESTROGEN-RECEPTOR; BRAIN METASTASES; THORACIC MANIFESTATIONS; PROGESTERONE-RECEPTOR; MOLECULAR SUBTYPES; BONE-SCINTIGRAPHY; CLINICAL-OUTCOMES; LOCAL RECURRENCE AB There is accumulating evidence that molecular phenotyping of breast cancer determines the timing, pattern, and outcome of metastatic disease. The most clinically relevant subtypes are hormonal-positive [oestrogen and progesterone receptor (ER/PR) positive], HER2 expressing, and triple-negative breast cancers (TNBCs). ER/PR-positive breast cancers demonstrate the best prognosis; however, metastases, in particular osseous disease, may develop much later. HER2expressing breast cancers, although aggressive, have improved outcomes due to the advent of HER2-targeted therapies, with increased risk of central nervous system (CNS) relapses later. Finally, TNBCs present in younger women, BRCA1 mutations carriers, and carry the worst overall prognosis, with high incidence of CNS metastases, especially during the first 5 years of diagnosis. It is important for radiologists to understand the nuances of these breast cancer subtypes to predict metastatic behaviours and guide possible imaging surveillance. (C) 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. C1 [Chikarmane, S. A.; Tirumani, S. H.; Howard, S. A.; Jagannathan, J. P.; DiPiro, P. J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Chikarmane, S. A.; Tirumani, S. H.; Howard, S. A.; Jagannathan, J. P.; DiPiro, P. J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Chikarmane, SA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM SCHIKARMANE@partners.org NR 66 TC 9 Z9 9 U1 1 U2 10 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0009-9260 EI 1365-229X J9 CLIN RADIOL JI Clin. Radiol. PD JAN PY 2015 VL 70 IS 1 BP 1 EP 10 DI 10.1016/j.crad.2014.08.015 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AY9JX UT WOS:000347867300001 PM 25300558 ER PT J AU Brennan, TV Lunsford, KE Vagefi, PA Bostrom, A Ma, M Feng, SD AF Brennan, Todd V. Lunsford, Keri E. Vagefi, Parsia A. Bostrom, Alan Ma, Michael Feng, Sandy TI Renal outcomes of simultaneous liver-kidney transplantation compared to liver transplant alone for candidates with renal dysfunction SO CLINICAL TRANSPLANTATION LA English DT Article DE kidney; liver; outcomes; renal dysfunction; transplantation ID HEPATORENAL-SYNDROME; MELD ERA; DISEASE; CIRRHOSIS; SURVIVAL; RECOVERY; FAILURE; INSUFFICIENCY; PREDICTORS; RECIPIENTS AB It is unclear whether a concomitant kidney transplant grants survival benefit to liver transplant (LT) candidates with renal dysfunction (RD). We retrospectively studied LT candidates without RD (n=714) and LT candidates with RD who underwent either liver transplant alone (RD-LTA; n=103) or simultaneous liver-kidney transplant (RD-SLKT; n=68). RD was defined as renal replacement therapy (RRT) requirement or modification of diet in renal disease (MDRD)-glomerular filtration rate (GFR) <25mL/min/1.73m(2). RD-LTAs had worse one-yr post-transplant survival compared to RD-SLKTs (79.6% vs. 91.2%, p=0.05). However, RD-LTA recipients more often had hepatitis C (60.2% vs. 41.2%, p=0.004) and more severe liver disease (MELD 37.9 +/- 8.1 vs. 32.7 +/- 9.1, p=0.0001). Twenty RD-LTA recipients died in the first post-transplant year. Evaluation of the cause and timing of death relative to native renal recovery revealed that only four RD-LTA recipients might have derived survival benefit from RD-SLKT. Overall, 87% of RD-LTA patients recovered renal function within onemonth of transplant. Oneyr after RD-LTA or RD-SLKT, serum creatinine (1.5 +/- 1.2mg/dL vs. 1.4 +/- 0.5mg/dL, p=0.63) and prevalence of stage 4 or 5 chronic kidney disease (CKD; 5.9% vs. 6.8%, p=0.11) were comparable. Our series provides little evidence that RD-SLKT would have yielded substantial short-term survival benefit to RD-LTA recipients. C1 [Brennan, Todd V.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Lunsford, Keri E.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Vagefi, Parsia A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Bostrom, Alan] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Ma, Michael; Feng, Sandy] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. RP Brennan, TV (reprint author), Duke Univ, Med Ctr, DUMC 3512, Durham, NC 27710 USA. EM todd.brennan@duke.edu FU American Society of Transplantation; American Association for the Study of Liver Disease FX This work was supported by grants from the American Society of Transplantation (T.V.B.) and the American Association for the Study of Liver Disease (T.V.B.). NR 33 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0902-0063 EI 1399-0012 J9 CLIN TRANSPLANT JI Clin. Transplant. PD JAN PY 2015 VL 29 IS 1 BP 34 EP 43 DI 10.1111/ctr.12479 PG 10 WC Surgery; Transplantation SC Surgery; Transplantation GA AY8AY UT WOS:000347778000005 PM 25328090 ER PT J AU Hill, DE Vasdev, N Holland, JP AF Hill, David E. Vasdev, Neil Holland, Jason P. TI Evaluating the accuracy of density functional theory for calculating H-1 and C-13 NMR chemical shifts in drug molecules SO COMPUTATIONAL AND THEORETICAL CHEMISTRY LA English DT Article DE NMR; Shielding constants; Chemical shifts; Density functional theory; Ispinesib; Kinesin spindle protein inhibitors ID SPIN COUPLING-CONSTANTS; GENERALIZED GRADIENT APPROXIMATION; EXCHANGE-CORRELATION FUNCTIONALS; CORRELATION-ENERGY; SHIELDING CONSTANTS; BASIS-SET; ORGANIC-MOLECULES; DFT CALCULATIONS; PBE0 MODEL; COMPUTATION AB The accuracy of different DFT methodologies for calculating H-1 and C-13 NMR chemical shifts in (R)-ispinesib, a complex drug molecule with multiple chemical groups and one stereocentre, has been evaluated. The accuracy of 6 basis sets and 16 different XC functionals was tested. In addition, we present a detailed study on the role of geometry optimisation (in gas and solution phase using a chloroform polarisable continuum model) on the accuracy of the calculated NMR spectra. NMR calculations using the double-4 basis sets DGDZVP and 6-31++G(d,p) were found to be mire accurate (and computationally more efficient) than those using larger triple-4 basis sets. The 03INP/DGDZVP methodology in solution phase using a geometry optimised at the same level of theory was found to be the most accurate method with mean absolute errors (MAEs) for 1H and 13C chemical shifts of 0.174 ppm and 3.972 ppm, respectively. Irrespective of the choice of XC or basis set used, complete geometry optimisation in either gas or solvent phase was found to be essential for attaining the highest accuracy in both 1H and 13C calculated chemical shifts. Finally, the role of molecular conformation was examined by calculating the Boltzmann-weighted 1H and 13C chemical shifts. Overall, we demonstrate that DFF shows exceptional promise for use in calculating the NMR chemical shifts in complex drug molecules. In the future, DFF calculations of NMR parameters are set to play an increasingly important role in drug discovery and chemical optimisation. (C) 2014 Elsevier B.V. All rights reserved. C1 [Hill, David E.; Vasdev, Neil; Holland, Jason P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Hill, David E.] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA. RP Holland, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Nucl Med & Mol Imaging, 55 Fruit St,White 427, Boston, MA 02114 USA. EM holland.jason@mgh.harvard.edu OI Holland, Jason/0000-0002-0066-219X FU Australian National Science and Technology Organisation (ANSTO, Sydney) FX We thank Dr. Thomas Betzel for technical assistance. We thank Dr. Eliane Fischer and Dr. T. Lee Collier for support with statistical analyses. We are grateful to the staff at the Massachusetts Green High Performance Computing Center (MGHPCC, Holyoke, MA, USA) and the Northeastern University Information Technology Service and Research Computing (Boston, USA; http://www.northeastern.eduirc) for providing technical support and access to the Discovery Cluster. We are grateful to Dr. Rein U. Kirss (Northeastern University) for supporting access to the MGHPCC (DEH). We thank Dr. Ivan Greguric and the Australian National Science and Technology Organisation (ANSTO, Sydney) for providing financial support (JPH). NR 84 TC 4 Z9 4 U1 2 U2 23 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2210-271X EI 1872-7999 J9 COMPUT THEOR CHEM JI Comput. Theor. Chem. PD JAN 1 PY 2015 VL 1051 BP 161 EP 172 DI 10.1016/j.comptc.2014.11.007 PG 12 WC Chemistry, Physical SC Chemistry GA AY9HT UT WOS:000347862000020 ER PT J AU Keane, TM AF Keane, Terence M. TI TOWARD A GREATER UNDERSTANDING OF MENTAL HEALTH ISSUES IN TODAY'S MILITARY SO DEPRESSION AND ANXIETY LA English DT Editorial Material ID SERVICEMEMBERS ARMY STARRS; ASSESS RISK; RESILIENCE; VETERANS; PTSD C1 [Keane, Terence M.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder,Dept Vet Aff, Boston, MA 02118 USA. RP Keane, TM (reprint author), VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, 150 S Huntington Ave, Boston, MA 02130 USA. EM terry.keane@va.gov NR 6 TC 0 Z9 0 U1 3 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD JAN PY 2015 VL 32 IS 1 BP 1 EP 2 DI 10.1002/da.22324 PG 2 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA AY9MI UT WOS:000347874800001 PM 25339117 ER PT J AU Quinn, KP Golberg, A Broelsch, GF Khan, S Villiger, M Bouma, B Austen, WG Sheridan, RL Mihm, MC Yarmush, ML Georgakoudi, I AF Quinn, Kyle P. Golberg, Alexander Broelsch, G. Felix Khan, Saiqa Villiger, Martin Bouma, Brett Austen, William G., Jr. Sheridan, Robert L. Mihm, Martin C., Jr. Yarmush, Martin L. Georgakoudi, Irene TI An automated image processing method to quantify collagen fibre organization within cutaneous scar tissue SO EXPERIMENTAL DERMATOLOGY LA English DT Article DE burns; collagen; fibre alignment; image analysis; scar remodelling ID MICE AB Standard approaches to evaluate scar formation within histological sections rely on qualitative evaluations and scoring, which limits our understanding of the remodelling process. We have recently developed an image analysis technique for the rapid quantification of fibre alignment at each pixel location. The goal of this study was to evaluate its application for quantitatively mapping scar formation in histological sections of cutaneous burns. To this end, we utilized directional statistics to define maps of fibre density and directional variance from Masson's trichrome-stained sections for quantifying changes in collagen organization during scar remodelling. Significant increases in collagen fibre density are detectable soon after burn injury in a rat model. Decreased fibre directional variance in the scar was also detectable between 3weeks and 6months after injury, indicating increasing fibre alignment. This automated analysis of fibre organization can provide objective surrogate endpoints for evaluating cutaneous wound repair and regeneration. C1 [Quinn, Kyle P.; Georgakoudi, Irene] Tufts Univ, Dept Biomed Engn, Medford, MA 02155 USA. [Golberg, Alexander; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Dept Surg, Boston, MA USA. [Golberg, Alexander; Yarmush, Martin L.] Shriners Burns Hosp, Boston, MA USA. [Golberg, Alexander] Tel Aviv Univ, Porter Sch Environm Studies, IL-69978 Tel Aviv, Israel. [Broelsch, G. Felix; Khan, Saiqa; Austen, William G., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg, Boston, MA USA. [Villiger, Martin; Bouma, Brett] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Sheridan, Robert L.] Shriners Hosp Children, Sumner Redstone Burn Ctr, Boston, MA USA. [Mihm, Martin C., Jr.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA. RP Quinn, KP (reprint author), Tufts Univ, Dept Biomed Engn, 4 Colby St, Medford, MA 02155 USA. EM kyle@quinnlab.org FU NIH [F32AR061933, R01EB007542]; American Cancer Society [RSG-09-174-01-CCE]; Shriners Grant [85120-BOS] FX This study was supported by NIH grant F32AR061933 to KPQ, American Cancer Society grant RSG-09-174-01-CCE to IG, NIH grant R01EB007542 to IG and Shriners Grant #85120-BOS to AG and MY. NR 9 TC 6 Z9 6 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0906-6705 EI 1600-0625 J9 EXP DERMATOL JI Exp. Dermatol. PD JAN PY 2015 VL 24 IS 1 BP 78 EP 80 DI 10.1111/exd.12553 PG 3 WC Dermatology SC Dermatology GA AY6WP UT WOS:000347703900021 PM 25256009 ER PT J AU Chauhan, SK Jurkunas, U Funaki, T Dastjerdi, M Dana, R AF Chauhan, S. K. Jurkunas, U. Funaki, T. Dastjerdi, M. Dana, R. TI Quantification of allospecific and nonspecific corneal endothelial cell damage after corneal transplantation SO EYE LA English DT Article ID CONTACT-LENS WEAR; PENETRATING KERATOPLASTY; ALLOGRAFT-REJECTION; GRAFT-SURVIVAL; T-CELLS; APOPTOSIS; CD4(+); DENSITY AB Purpose To investigate the effect of host immunity (allospecific) and surgical manipulation (non-allospecific) on corneal endothelial cells (CECs) in corneal transplantation. Methods Draining lymph nodes and grafted C57BL/6 corneas were harvested from syngeneic recipients, allograft acceptors, and allograft rejectors (BALB/c) 1, 3, and 8 weeks after transplantation. We analyzed CEC apoptosis using an ex vivo cornea-in-the-cup assay, and visualized cell-to-cell junctions using immunohistochemical staining (ZO-1). Automatic cell analysis using Confoscan software was used to measure CEC density as well as changes in CEC morphology by quantifying the coefficient of variation in cell size (polymegethism) and shape (pleomorphism). Results The cornea-in-the-cup assay showed that allogeneic acceptor T cells and to an even greater extent rejector T cells (but not syngeneic T cells) induced CEC apoptosis. CEC density after corneal transplantation was significantly reduced in allogeneic acceptors compared with syngeneic grafts (P < 0.001), and CEC density was even further reduced in the allo-rejector group compared with the allo-acceptor group. Allogeneic grafts showed a greater increase in the coefficient of variation in cell size (polymegethism) when compared with syngeneic grafts 1 week after transplantation (P = P < 0.001). However, pleomorphism was not significantly different between syngeneic and allo-acceptor grafts, indicating that polymegethism (but not pleomorphism or cell density) is a sensitive indicator of the effect of alloimmunity on CECs. Conclusions Our data demonstrate that host alloimmunity rather than surgical manipulation alone is the major cause of CEC damage in corneal transplantation, and such morphologic changes of CECs can be detected before the clinically visible onset of allograft rejection. C1 [Chauhan, S. K.] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. [Chauhan, S. K.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Chauhan, SK (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM sunil_chauhan@meei.harvard.edu FU [NIH/NEI-EY12963] FX We thank Dr Susanne Eiglmeier, PhD, Schepens Eye Research Institute, Boston for assisting in editing and formatting this manuscript. This work was supported by NIH/NEI-EY12963 (to RD). NR 30 TC 2 Z9 2 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X EI 1476-5454 J9 EYE JI Eye PD JAN PY 2015 VL 29 IS 1 BP 136 EP 144 DI 10.1038/eye.2014.248 PG 9 WC Ophthalmology SC Ophthalmology GA AY8FJ UT WOS:000347789500013 PM 25323855 ER PT J AU Evron, Y Zimermann, B Ludwig, B Barkai, U Colton, CK Weir, GC Arieli, B Maimon, S Shalev, N Yavriyants, K Goldman, T Gendler, Z Eizen, L Vardi, P Bloch, K Barthel, A Bornstein, SR Rotem, A AF Evron, Y. Zimermann, B. Ludwig, B. Barkai, U. Colton, C. K. Weir, G. C. Arieli, B. Maimon, S. Shalev, N. Yavriyants, K. Goldman, T. Gendler, Z. Eizen, L. Vardi, P. Bloch, K. Barthel, A. Bornstein, S. R. Rotem, A. TI Oxygen Supply by Photosynthesis to an Implantable Islet Cell Device SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE type 1 diabetes; bioartificial pancreas; cyanobacteria ID RAT PANCREATIC-ISLETS; BIOARTIFICIAL PANCREAS; INSULIN-SECRETION; EDMONTON PROTOCOL; TRANSPLANTATION; LANGERHANS; HYPOXIA; GROWTH; TEMPERATURE; MORTALITY AB Transplantation of islet cells is an effective treatment for type 1 diabetes with critically labile metabolic control. However, during islet isolation, blood supply is disrupted, and the transport of nutrients/metabolites to and from the islet cells occurs entirely by diffusion. Adequate oxygen supply is essential for function/survival of islet cells and is the limiting factor for graft integrity. Recently, we developed an immunoisolated chamber system for transplantation of human islets without immunosuppression. This system depended on daily oxygen supply. To provide independence from this external source, we incorporated a novel approach based on photosynthetically-generated oxygen. The chamber system was packed sandwich-like with a slab of immobilized photosynthetically active microorganisms (Synechococcus lividus) on top of a flat light source (LEDs, red light at 660nm, intensity of 8E/m(2)/s). Islet cells immobilized in an alginate slab (500-1000 islet equivalents/cm(2)) were mounted on the photosynthetic slab separated by a gas permeable silicone rubber-Teflon membrane, and the complete module was sealed with a microporous polytetrafluorethylene (Teflon) membrane (pore size: 0.4m) to protect the contents from the host immune cells. Upon illumination, oxygen produced by photosynthesis diffused via the silicone Teflon membrane into the islet compartment. Oxygen production from implanted encapsulated microorganisms was stable for 1 month. After implantation of the device into diabetic rats, normoglycemia was achieved for 1 week. Upon retrieval of the device, blood glucose levels returned to the diabetic state. Our results demonstrate that an implanted photosynthetic bioreactor can supply oxygen to transplanted islets and thus maintain islet viability/functionality. C1 [Evron, Y.; Zimermann, B.; Ludwig, B.; Barkai, U.; Arieli, B.; Maimon, S.; Shalev, N.; Yavriyants, K.; Goldman, T.; Gendler, Z.; Eizen, L.; Rotem, A.] Beta O2 Technol Ltd, IL-480990 Rosh Haain, Afek Park, Israel. [Ludwig, B.; Barthel, A.; Bornstein, S. R.] Univ Hosp Carl Gustav Carus, Dept Med 3, Dresden, Germany. [Colton, C. K.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Weir, G. C.] Joslin Diabet Ctr, Div Res, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. [Vardi, P.; Bloch, K.] Tel Aviv Univ, Diabet & Obes Res Lab, Felsenstein Med Res Ctr, Sackler Fac Med, Petah Tiqwa, Israel. [Barthel, A.] Endokrinol Ruhr, Bochum, Germany. RP Rotem, A (reprint author), Beta O2 Technol Ltd, 11 Haamal St,POB 11793, IL-480990 Rosh Haain, Afek Park, Israel. EM avi@beta-o2.com NR 34 TC 3 Z9 3 U1 1 U2 9 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 EI 1439-4286 J9 HORM METAB RES JI Horm. Metab. Res. PD JAN PY 2015 VL 47 IS 1 BP 24 EP 30 DI 10.1055/s-0034-1394375 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AY8JY UT WOS:000347801000005 PM 25365509 ER PT J AU Gandaglia, G Karakiewicz, PI Briganti, A Trudeau, V Trinh, QD Kim, SP Montorsi, F Nguyen, PL Abdollah, F Sun, M AF Gandaglia, Giorgio Karakiewicz, Pierre I. Briganti, Alberto Trudeau, Vincent Quoc-Dien Trinh Kim, Simon P. Montorsi, Francesco Nguyen, Paul L. Abdollah, Firas Sun, Maxine TI Early radiotherapy after radical prostatectomy improves cancer-specific survival only in patients with highly aggressive prostate cancer: Validation of recently released criteria SO INTERNATIONAL JOURNAL OF UROLOGY LA English DT Article DE adjuvant radiotherapy; cancer-specific survival; competing-risks; early radiotherapy; prostate cancer; radical prostatectomy; risk score ID SALVAGE RADIATION-THERAPY; TERM-FOLLOW-UP; ADJUVANT RADIOTHERAPY; MULTIINSTITUTIONAL ANALYSIS; RISK; METASTASES; POPULATION; IMPACT; TRIAL AB ObjectivesTo test the effect of radiotherapy administered within 6 months after radical prostatectomy on cancer-specific mortality in prostate cancer patients after stratification according to a risk score. MethodsOverall, 7616 patients with pT3/4 N0/1 prostate cancer treated with radical prostatectomy between 1995 and 2009 within the Surveillance Epidemiology and End Results Medicare-linked database were included in the study. Competing-risks regression models were carried out to test the effect of early radiotherapy on cancer-specific mortality in the entire cohort, and after stratifying patients according to the risk score based on the number and nature of adverse pathological characteristics (Gleason score 8-10; pT3b/4, lymph node invasion). ResultsThe risk score was associated with increasing 5- and 10-year cancer-specific mortality rates (P<0.001). When considering only patients with a risk score 2, 5- and 10-year cancer-specific mortality rates were significantly lower for individuals undergoing early radiotherapy compared with their counterparts not receiving early radiotherapy (2.9 and 6.9 vs 5.7 and 16.2%, respectively; P=0.002). The corresponding number required to treat to prevent one death from prostate cancer at 10-year follow up was 10. Early radiotherapy was not associated with lower cancer-specific mortality rates overall and in patients with a risk score <2. This was confirmed in multivariable analyses, where early radiotherapy decreased the risk of cancer-specific mortality only in patients with a risk score 2 (P0.02). ConclusionsThe presence of two or more of the following pathological features might be used to identify patients who benefit from early radiotherapy: Gleason score 8-10, pT3b/4 and lymph node invasion. C1 [Gandaglia, Giorgio; Karakiewicz, Pierre I.; Trudeau, Vincent; Sun, Maxine] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ H2X 3J4, Canada. [Gandaglia, Giorgio; Briganti, Alberto; Montorsi, Francesco; Abdollah, Firas] Univ Vita Salute San Raffaele, Dept Urol, Milan, Italy. [Quoc-Dien Trinh; Nguyen, Paul L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg,Div Urol,Dana Farber Canc Inst, Boston, MA 02115 USA. [Kim, Simon P.] Yale Univ, Dept Urol, New Haven, CT USA. RP Gandaglia, G (reprint author), Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, 1058 Rue St Denis, Montreal, PQ H2X 3J4, Canada. EM giorgio.gandaglia@gmail.com FU University of Montreal Health Center Urology Specialists; Fonds de la Recherche en Sante du Quebec; University of Montreal Department of Surgery; University of Montreal Health Centre (CHUM) Foundation FX Pierre I Karakiewicz is partially supported by the University of Montreal Health Center Urology Specialists, Fonds de la Recherche en Sante du Quebec, the University of Montreal Department of Surgery and the University of Montreal Health Centre (CHUM) Foundation. NR 29 TC 7 Z9 7 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0919-8172 EI 1442-2042 J9 INT J UROL JI Int. J. Urol. PD JAN PY 2015 VL 22 IS 1 BP 89 EP 95 DI 10.1111/iju.12605 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA AY8QZ UT WOS:000347819700021 PM 25141965 ER PT J AU Eswara, JR Gervais, DA Mueller, PR Arellano, RS Cantwell, CP McGovern, FJ AF Eswara, Jairam R. Gervais, Debra A. Mueller, Peter R. Arellano, Ronald S. Cantwell, Colin P. McGovern, Francis J. TI Renal radiofrequency ablation with pyeloperfusion SO INTERNATIONAL JOURNAL OF UROLOGY LA English DT Editorial Material C1 [Eswara, Jairam R.; McGovern, Francis J.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Gervais, Debra A.; Mueller, Peter R.; Arellano, Ronald S.; Cantwell, Colin P.] Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP Eswara, JR (reprint author), Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. EM jeswara@partners.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0919-8172 EI 1442-2042 J9 INT J UROL JI Int. J. Urol. PD JAN PY 2015 VL 22 IS 1 BP 131 EP 132 DI 10.1111/iju.12625 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA AY8QZ UT WOS:000347819700032 PM 25236857 ER PT J AU Smith, KM Eyal, E Weintraub, D AF Smith, Kara M. Eyal, Eli Weintraub, Daniel CA ADAGIO Investigators TI Combined Rasagiline and Antidepressant Use in Parkinson Disease in the ADAGIO Study Effects on Nonmotor Symptoms and Tolerability SO JAMA NEUROLOGY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; MAJOR DEPRESSIVE DISORDER; DELAYED-START TRIAL; DOUBLE-BLIND; PRAMIPEXOLE; SCALE; AUGMENTATION; METAANALYSIS; SELEGILINE; INHIBITOR AB IMPORTANCE Depression, cognitive impairment, and other nonmotor symptoms (NMSs) are common early in Parkinson disease (PD) and may be in part due to disease-related dopamine deficiency. Many patients with PD are treated with antidepressants for NMSs, and the effect of the combination of PD medications that enhance dopamine neurotransmission and antidepressants on NMSs has not been studied. We report the effects of the addition of a monoamine oxidase B inhibitor, rasagiline, to antidepressant treatment in PD. OBJECTIVE To evaluate the effect of rasagiline on depression, cognition, and other PD NMSs in patients taking an antidepressant in the Attenuation of Disease Progression With Azilect Given Once Daily (ADAGIO) study. DESIGN, SETTING, AND PARTICIPANTS The ADAGIO study was a double-blind, placebo-controlled, delayed-start trial of rasagiline in de novo PD. In this exploratory post hoc analysis, we analyzed patients taking an antidepressant during the 36-week phase 1 period, in which patients were randomized to rasagiline (1 or 2mg/d) or placebo. MAIN OUTCOMES AND MEASURES We evaluated the change in NMSs in patients taking an antidepressant and rasagiline compared with those taking placebo. The NMSs were assessed by Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale Nonmotor Experiences of Daily Living, the original Unified Parkinson's Disease Rating Scale, and the Parkinson Fatigue Scale. RESULTS A total of 191 of the 1174 patients (16.3%) were treated with antidepressants during phase 1 and provided efficacy data. Depression and cognition scores revealed significantly less worsening in the rasagiline group compared with the placebo group (differences in Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale item-adjusted means [SEs], -0.19 [0.10], P = .048, and -0.20 [0.05], P < .001, respectively). Parkinson Fatigue Scale (mean [SE] difference, -0.42 [0.09], P < .001) and daytime sleepiness (mean [SE] difference, -0.24 [0.09], P = .006) scores also revealed significantly less worsening in the rasagiline group compared with placebo. There was a nonsignificant trend toward less worsening in apathy and no significant between-group differences in anxiety or sleep. The effect on depression remained significant after controlling for improvement in motor symptoms (mean [SE] difference, -0.23 [0.09], P = .009). There were no serious adverse events in the combined rasagiline-antidepressant group suggestive of serotonin syndrome. CONCLUSIONS AND RELEVANCE The combination of rasagiline and antidepressants in patients with de novo PD is associated with reduced worsening of a range of NMSs in preliminary analyses. Adverse effects appear uncommon with this combination. These findings suggest a role for dopamine-enhancing therapies in NMSs in early PD and encourage further study and confirmation. C1 [Smith, Kara M.; Weintraub, Daniel] Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19107 USA. [Eyal, Eli] Teva Pharmaceut Ind, Petah Tiqwa, Israel. [Weintraub, Daniel] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19107 USA. [Weintraub, Daniel] Philadelphia VA Med Ctr, Dept Vet Affairs, Philadelphia, PA USA. RP Smith, KM (reprint author), Univ Penn, Dept Neurol, Perelman Sch Med, 330 S Ninth St, Philadelphia, PA 19107 USA. EM kara.smith@uphs.upenn.edu RI Deuschl, Gunther/A-7986-2010; OI Schnitzler, Alfons/0000-0002-6414-7939; Calopa, Matilde/0000-0002-6943-3707 FU Teva Pharmaceuticals FX The ADAGIO study was funded by Teva Pharmaceuticals. NR 40 TC 19 Z9 21 U1 4 U2 19 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD JAN PY 2015 VL 72 IS 1 BP 88 EP 95 DI 10.1001/jamaneurol.2014.2472 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA AY8PI UT WOS:000347815300014 PM 25420207 ER PT J AU Christen, WG Glynn, RJ Gaziano, JM Darke, AK Crowley, JJ Goodman, PJ Lippman, SM Lad, TE Bearden, JD Goodman, GE Minasian, LM Thompson, IM Blanke, CD AF Christen, William G. Glynn, Robert J. Gaziano, J. Michael Darke, Amy K. Crowley, John J. Goodman, Phyllis J. Lippman, Scott M. Lad, Thomas E. Bearden, James D. Goodman, Gary E. Minasian, Lori M. Thompson, Ian M., Jr. Blanke, Charles D. TI Age-Related Cataract in Men in the Selenium and Vitamin E Cancer Prevention Trial Eye Endpoints Study A Randomized Clinical Trial SO JAMA OPHTHALMOLOGY LA English DT Article ID GLUTATHIONE-PEROXIDASE ACTIVITY; SENILE CATARACT; ANTIOXIDANT VITAMINS; PROSTATE-CANCER; PROTECTIVE ROLE; LENS OPACITIES; BETA-CAROTENE; FINNISH MEN; SUPPLEMENTATION; SELECT AB IMPORTANCE Observational studies suggest a role for dietary nutrients such as vitamin E and selenium in cataract prevention. However, the results of randomized clinical trials of vitamin E supplements and cataract have been disappointing and are not yet available for selenium. OBJECTIVE To test whether long-term supplementation with selenium and vitamin E affects the incidence of cataract in a large cohort of men. DESIGN, SETTING, AND PARTICIPANTS The Selenium and Vitamin E Cancer Prevention Trial (SELECT) Eye Endpoints Study was an ancillary study of the Southwest Oncology Group-coordinated SELECT, a randomized placebo-controlled 4-arm trial of selenium and vitamin E conducted among 35 533 men, 50 years and older for African American participants and 55 years and older for all other men, at 427 participating sites in the United States, Canada, and Puerto Rico. A total of 11 267 SELECT participants from 128 SELECT sites participated in the SELECT Eye Endpoints ancillary study. INTERVENTIONS Individual supplements of selenium (200 mu g per day from L-selenomethionine) and vitamin E (400 IU per day of all rac-a-tocopheryl acetate). MAIN OUTCOMES AND MEASURES Incident cataract was defined as a lens opacity, age related in origin, and responsible for a reduction in best-corrected visual acuity to 20/30 or worse based on self-reports confirmed by medical record review. Cataract extraction was defined as the surgical removal of an incident cataract. RESULTS During a mean (SD) of 5.6 (1.2) years of treatment and follow-up, 389 cases of cataract were documented. There were 185 cataracts in the selenium group and 204 in the no selenium group (hazard ratio, 0.91; 95% CI, 0.75-1.11; P =.37). For vitamin E, there were 197 cases in the treated group and 192 in the placebo group (hazard ratio, 1.02; 95% CI, 0.84-1.25; P =.81). Similar results were observed for cataract extraction. CONCLUSIONS AND RELEVANCE These data from a large cohort of apparently healthy men indicate that long-term daily supplementation with selenium and/or vitamin E is unlikely to have a large beneficial effect on age-related cataract. C1 [Christen, William G.; Glynn, Robert J.; Gaziano, J. Michael] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Prevent Med, Boston, MA 02215 USA. [Gaziano, J. Michael] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Aging, Boston, MA 02215 USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Darke, Amy K.; Crowley, John J.; Goodman, Phyllis J.] Fred Hutchinson Canc Res Ctr, Southwest Oncol Grp Stat Ctr, Seattle, WA 98104 USA. [Lippman, Scott M.] Univ Calif San Diego, Moores Canc Ctr, Off Director, San Diego, CA 92103 USA. [Lad, Thomas E.] Jesse Brown VA Med Ctr, Chicago, IL USA. [Bearden, James D.] Spartanburg Reg Med Ctr, Upstate Carolina Community Clin Oncol Program, Spartanburg, SC USA. [Goodman, Gary E.] Swedish Med Ctr, Washington, DC USA. [Minasian, Lori M.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Thompson, Ian M., Jr.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, Dept Urol, San Antonio, TX 78229 USA. [Blanke, Charles D.] Oregon Hlth & Sci Univ, Knight Canc Inst, Southwest Oncol Grp Chairs Off, Portland, OR 97201 USA. [Blanke, Charles D.] Cleveland Clin, Glickman Urol & Kidney Inst, Dept Urol, Cleveland, OH 44106 USA. RP Christen, WG (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. EM wchristen@rics.bwh.harvard.edu FU Public Health Service - National Cancer Institute, National Institutes of Health, Department of Health and Human Services [CA37429]; National Center for Complementary and Alternative Medicine; [EY014418] FX This work was supported by grant EY014418 and in part by grant CA37429 from the Public Health Service Cooperative Agreement awarded by the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, and the National Center for Complementary and Alternative Medicine. NR 43 TC 10 Z9 10 U1 0 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD JAN PY 2015 VL 133 IS 1 BP 17 EP 24 DI 10.1001/jamaophthalmol.2014.3478 PG 8 WC Ophthalmology SC Ophthalmology GA AZ1AJ UT WOS:000347972500003 PM 25232809 ER PT J AU Jakobiec, FA Rashid, A Lewis, K AF Jakobiec, Frederick A. Rashid, Alia Lewis, Kyle TI Massive Retinal Gliosis in Neurofibromatosis Type 1 SO JAMA OPHTHALMOLOGY LA English DT Letter ID MANIFESTATIONS C1 [Jakobiec, Frederick A.; Rashid, Alia] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, David G Cogan Lab Ophthalm Pathol, Boston, MA USA. [Lewis, Kyle] Univ Mississippi, Oculoplast Serv, Med Ctr, Jackson, MS USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, Lab Ophthalm Pathol, 243 Charles St, Boston, MA 02114 USA. EM fred_jakobiec@meei.harvard.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD JAN PY 2015 VL 133 IS 1 BP 100 EP 102 DI 10.1001/jamaophthalmol.2014.3958 PG 3 WC Ophthalmology SC Ophthalmology GA AZ1AJ UT WOS:000347972500018 PM 25317586 ER PT J AU Kozin, ED Cummings, BM Rogers, DJ Lin, B Sethi, R Noviski, N Hartnick, CJ AF Kozin, Elliott D. Cummings, Brian M. Rogers, Derek J. Lin, Brian Sethi, Rosh Noviski, Natan Hartnick, Christopher J. TI Systemwide Change of Sedation Wean Protocol Following Pediatric Laryngotracheal Reconstruction SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID INTENSIVE-CARE-UNIT; CRITICALLY-ILL CHILDREN; POSTOPERATIVE MANAGEMENT; SINUS SURGERY; CHECKLIST; IMPLEMENTATION; OTOLARYNGOLOGY; CONSEQUENCES; WITHDRAWAL; TOLERANCE AB IMPORTANCE Pediatric laryngotracheal reconstruction (LTR) remains the standard surgical technique for expanding a stenotic airway and necessitates a multidisciplinary team. Sedation wean following LTR is a critical component of perioperative care. We identified variation and communications deficiencies with our sedation wean practice and describe our experience implementing a standardized sedation wean protocol. OBJECTIVE To standardize and decrease length of sedation wean in pediatric patients undergoing LTR. DESIGN, SETTING, AND PARTICIPANTS Using Institute for Healthcare Improvement (IHI) methodology, we implemented systemwide change at a tertiary care center with the goal of improving care based on best practice guidelines. We created a standardized electronic sedation wean communication document and retrospectively examined our experience in 29 consecutive patients who underwent LTR before (n = 16, prewean group) and after (n = 13, postwean group) wean document implementation. INTERVENTIONS Implementation of a standardized sedation protocol. MAIN OUTCOMES AND MEASURES Presence of sedation wean document in the electronic medical record, length of sedation wean, and need for continued wean after discharge. RESULTS The sedation wean document was used in 92.3% patients in the postwean group. With the new process, the mean (SD) length of sedation wean was reduced from 16.19 (11.56) days in the prewean group to 8.92 (3.37) days in the postwean group (P = .045). Fewer patients in the postwean group required continued wean after discharge (81.3% vs 33.3%; P = .02). CONCLUSIONS AND RELEVANCE We implemented a systemwide process change with the goal of improving care based on best practice guidelines, which significantly decreased the time required for sedation wean following LTR. Our methodological approach may have implications for other heterogeneous patient populations requiring a sedation wean. C1 [Kozin, Elliott D.; Rogers, Derek J.; Lin, Brian; Sethi, Rosh; Hartnick, Christopher J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Kozin, Elliott D.; Rogers, Derek J.; Lin, Brian; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Cummings, Brian M.; Noviski, Natan] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Christopher_Hartnick@meei.harvard.edu RI Kozin, Elliott/J-1225-2014 OI Kozin, Elliott/0000-0002-0305-0682 FU NIDCD NIH HHS [T32 DC000020] NR 36 TC 2 Z9 2 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6181 EI 2168-619X J9 JAMA OTOLARYNGOL JI JAMA Otolaryngol-Head Neck Surg. PD JAN PY 2015 VL 141 IS 1 BP 27 EP 33 DI 10.1001/jamaoto.2014.2694 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA AZ1AQ UT WOS:000347973300004 PM 25356601 ER PT J AU Gandhi, PU Szymonifka, J Motiwala, SR Belcher, AM Januzzi, JL Gaggin, HK AF Gandhi, Parul U. Szymonifka, Jackie Motiwala, Shweta R. Belcher, Arianna M. Januzzi, James L., Jr. Gaggin, Hanna K. TI Characterization and Prediction of Adverse Events From Intensive Chronic Heart Failure Management and Effect on Quality of Life: Results From the Pro-B-Type Natriuretic Peptide Outpatient-Tailored Chronic Heart Failure Therapy (PROTECT) Study SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Heart failure; natriuretic peptides; medication ID BETA-BLOCKER THERAPY; DYSFUNCTION; SURVIVAL; PATIENT; TIME AB Background: Serious adverse events (SAEs) from heart failure (HF) therapy are frequent; however, techniques to identify at-risk patients are inadequate. Furthermore, the relationship between SAEs, quality of life (QOL), and cardiac structure are unknown. Methods and Results: 151 symptomatic patients with systolic HF were followed for a mean of 10 months. In this post hoc analysis, treatment-related SAEs included acute renal failure, dizziness, hypo/hyperkalemia, hypotension, and syncope. At 1 year, 21 treatment-related SAEs occurred. No difference in SAEs existed between the N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided arm and the standard of care arm (P = .20). At baseline, patients who suffered SAEs were less likely to be receiving beta-blockers (85.7% vs 97.7%; P = .009) and had worse functional class and lower chloride levels. Patients who experienced SAEs had less improvement in their Minnesota Living With Heart Failure Questionnaire scores and had a trend toward reduced echocardiographic reverse remodeling over the follow-up period. Univariable and multivariable analyses were conducted to develop a risk score for SAE prediction; patients in the highest risk quartile had the shortest time to first cardiovascular event (P = 0.01). Conclusions: NT-proBNP guided HF care is safe. Experiencing treatment-related SAEs is associated with worse QOL and potentially reduced reverse remodeling. A risk score to prospectively predict SAEs in aggressive HF management was developed. C1 [Gandhi, Parul U.; Szymonifka, Jackie; Belcher, Arianna M.; Januzzi, James L., Jr.; Gaggin, Hanna K.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Motiwala, Shweta R.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Gaggin, HK (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Yawkey 5B, Boston, MA 02114 USA. EM hgaggin@mgh.harvard.edu FU Roche Diagnostics; Dennis and Marilyn Barry Fellowship in Cardiology; Clark Fund for Cardiac Research Innovation; Roman W. DeSanctis Clinical Scholar Endowment FX This study was partially supported by Roche Diagnostics, which had no role in the analysis of data or preparation of this manuscript. Drs Gandhi and Motiwala are supported by the Dennis and Marilyn Barry Fellowship in Cardiology, Dr Gaggin in part by the Clark Fund for Cardiac Research Innovation, and Dr Januzzi in part by the Roman W. DeSanctis Clinical Scholar Endowment. NR 19 TC 2 Z9 3 U1 0 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 EI 1532-8414 J9 J CARD FAIL JI J. Card. Fail. PD JAN PY 2015 VL 21 IS 1 BP 9 EP 15 DI 10.1016/j.cardfail.2014.10.008 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AY9KR UT WOS:000347869300003 PM 25463415 ER PT J AU Collins, S Storrow, AB Albert, NM Butler, J Ezekowitz, J Felker, GM Fermann, GJ Fonarow, GC Givertz, MM Hiestand, B Hollander, JE Fonarow, GC Givertz, MM Hiestand, B Hollander, JE Lanfear, DE Levy, PD Pang, PS Peacock, WF Sawyer, DB Teerlink, JR Lenihan, DJ AF Collins, Sean Storrow, Alan B. Albert, Nancy M. Butler, Javed Ezekowitz, Justin Felker, G. Michael Fermann, Gregory J. Fonarow, Gregg C. Givertz, Michael M. Hiestand, Brian Hollander, Judd E. Fonarow, Gregg C. Givertz, Michael M. Hiestand, Brian Hollander, Judd E. Lanfear, David E. Levy, Phillip D. Pang, Peter S. Peacock, W. Frank Sawyer, Douglas B. Teerlink, John R. Lenihan, Daniel J. CA SAEM HFSA Acute Heart Failure TI Early Management of Patients With Acute Heart Failure: State of the Art and Future Directions. A Consensus Document From the Society for Academic Emergency Medicine/Heart Failure Society of America Acute Heart Failure Working Group SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Acute heart failure; emergency medicine; early management ID BRAIN NATRIURETIC PEPTIDE; RANDOMIZED CONTROLLED-TRIAL; IN-HOSPITAL MORTALITY; PULMONARY ARTERIAL-HYPERTENSION; RIGHT-VENTRICULAR DYSFUNCTION; PRESERVED SYSTOLIC FUNCTION; NATIONAL REGISTRY ADHERE; BEDSIDE ULTRASOUND INBU; END-DIASTOLIC PRESSURE; INTENSIVE-CARE-UNIT AB Heart failure (HF) afflicts nearly 6 million Americans, resulting in one million emergency department (ED) visits and over one million annual hospital discharges. An aging population and improved survival from cardiovascular diseases is expected to further increase I-IF prevalence. Emergency providers play a significant role in the management of patients with acute heart failure (AHF). It is crucial that emergency physicians and other providers involved in early management understand the latest developments in diagnostic testing, therapeutics and alternatives to hospitalization. Further, clinical trials must be conducted in the ED in order to improve the evidence base and drive optimal initial therapy for ARE Should ongoing and future studies suggest early phenotype-driven therapy improves in-hospital and post-discharge outcomes, ED treatment decisions will need to evolve accordingly. The potential impact of future studies which incorporate risk-stratification into ED disposition decisions cannot be underestimated. Predictive instruments that identify a cohort of patients safe for ED discharge, while simultaneously addressing barriers to successful outpatient management, have the potential to significantly impact quality of life and resource expenditures. C1 [Collins, Sean] Nashville Vet Affairs Med Ctr, Nashville, TN USA. [Collins, Sean; Storrow, Alan B.; Sawyer, Douglas B.; Lenihan, Daniel J.] Vanderbilt Univ, Nashville, TN 37232 USA. [Albert, Nancy M.] Cleveland Clin, Cleveland, OH 44106 USA. [Butler, Javed] Emory Univ, Atlanta, GA 30322 USA. [Ezekowitz, Justin] Univ Alberta, Edmonton, AB, Canada. [Felker, G. Michael] Duke Univ, Durham, NC USA. [Fermann, Gregory J.] Univ Cincinnati, Cincinnati, OH USA. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Los Angeles, CA USA. [Givertz, Michael M.] Harvard Univ, Sch Med, Boston, MA USA. [Hiestand, Brian] Wake Forest Univ, Winston Salem, NC 27109 USA. [Hollander, Judd E.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Lanfear, David E.] Henry Ford Hosp, Detroit, MI 48202 USA. [Levy, Phillip D.] Wayne State Univ, Detroit, MI USA. [Pang, Peter S.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Peacock, W. Frank] Baylor Coll Med, Houston, TX 77030 USA. [Teerlink, John R.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. RP Collins, S (reprint author), Vanderbilt Univ, Dept Emergency Med, 1313 21st Ave South, Nashville, TN 37232 USA. EM sean.collins@vanderbilt.edu RI Ezekowitz, Justin/C-4579-2013; OI Ezekowitz, Justin/0000-0002-2724-4086; Hollander, Judd/0000-0002-1318-2785 FU National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) [K23HL085387]; Medtronic; Cardiorentis; Abbott Point-of-Care; Novartis; Medicines Company; Astellas; Intersection Medical; Radiometer; Abbott Diagnostics; Centers for Medicaid and Medicare Services (CMS); NIH/NHLBI [K12HL1090]; National Center for Advancing Translational Sciences [UL1TR000445]; Roche Diagnostics; NIH [RO10HL105448, U-10HL110312]; European Union; Health Resources and Services Administration; Amgen; Trevena; Portola; Siemens; Insys; Mayday Fund Pfizer; NHLBI; Sanofi Aventis; Dyax; Novartis Pharmaceuticals; Trevena, Inc.; Mespere; BG Medicine; NIH/NIMHD [5 R01 MD005849-04]; Abbott; Alere; Banyan; Roche; Acorda Therapeutics; Cardio3 Bioscience; Cytokinetics; Sorbent Therapeutics; St Jude FX Sean Collins: research support: National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) (K23HL085387), Medtronic, Cardiorentis, Abbott Point-of-Care, Novartis, The Medicines Company, Astellas, Intersection Medical, Radiometer; consultant: Trevena, Novartis, Otsuka, Radiometer, The Medicines Company, Medtronic, Brahms, Insys, Intersection Medical, Cardioxyl. Alan B. Storrow: current or recent grant support: Abbott Diagnostics, Centers for Medicaid and Medicare Services (CMS), NIH/NHLBI (K12HL1090), National Center for, Advancing Translational Sciences (UL1TR000445), Roche Diagnostics; current consultant: Roche Diagnostics, Novartis Pharmaceuticals Corp USA, Alere Diagnostics, Trevena, Beckman Coulter. Nancy Albert: none. Javed Butler: research support: NIH, European Union, Health Resources and Services Administration; consultant: Amgen, Bayer, BG Medicine, Cardiocell, Celladon, Gambro, GE Healthcare, Medtronic, Novartis, Ono Pharma, Takeda, Trevena, Zensun. Justin A. Ezekowitz: conflicts available online at www.vigour.ualberta.ca. G. Michael Felker: consultant: Novartis, Amgen, Trevena, Roche Diagnostics, Singulex, Sorbent Therapeutics, BMS; research funding NIH (RO10HL105448, U-10HL110312), Novartis, Amgen, Roche Diagnostics. Gregory J. Fermann: research support: Novartis, Cardiorentis, Trevena, Portola, Radiometer, Medtronic, Siemens, Insys, The Mayday Fund Pfizer; advisory board: Intersection Medical, Janssen, Insys, The Medicines Company. Gregg C. Fonarow: consultant: Medtronic, Novartis, Johnson and Johnson. Michael M. Givertz: scientific advisory board: Merck, Janssen, Cardioxyl; grant support: NHLBI. Brian Hiestand: consultant: Motive Medical Intelligence, Insight PD, Intersection Medical; advisory board: Janssen Pharmaceuticals; research funding: The Medicines Company, Sanofi Aventis, Dyax, Radiometer, Cardiorentis, Novartis. Judd Hollander: Consultant: Novartis. David Lanfear: consultant: Bayer, Otsuka, Covis, Biocontrol, Janssen. Phillip D. Levy: consultant: Novartis Pharmaceuticals, Trevena, Intersection Medical, The Medicines Company, Ostuka, Janssen, Astellas, Astrazeneca, Beckman Coulter, research support: Novartis Pharmaceuticals; Cardiorentis, Trevena, Inc., Intersection Medical, Mespere, BG Medicine, NIH/NIMHD (5 R01 MD005849-04). Peter S. Pang: consultant: Janssen, Medtronic, Novartis, Trevena, Springleaftx, BG Medicine, Cornerstone Therapeutics; research support Abbott, Alere, NIH. W. Frank Peacock: research support: Abbott, Alere, Banyan, Cardiorentis, Portola, Roche, The Medicines Company; consultant: BG Medicine, Beckman, Boehringer-Ingelheim, Instrument Labs, The Medicines Company; consultant: Alere, Cardiorentis, Janssen; ownership interests: Comprehensive Research Associates, Emergencies in Medicine. Douglas B. Sawyer: grant support and consultant: Acorda Therapeutics. John R. Teerlink: consulting fees and research grants: Amgen, Cardio3 Bioscience, Cytokinetics, Novartis, Sorbent Therapeutics, St Jude, Trevena. Daniel J. Lenihan: none. NR 163 TC 15 Z9 15 U1 1 U2 10 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 EI 1532-8414 J9 J CARD FAIL JI J. Card. Fail. PD JAN PY 2015 VL 21 IS 1 BP 27 EP 43 DI 10.1016/j.cardfail.2014.07.003 PG 17 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AY9KR UT WOS:000347869300006 PM 25042620 ER PT J AU Pendergraft, WF Means, TK AF Pendergraft, William F., III Means, Terry K. TI AGS, SLE, and RNASEH2 mutations: translating insights into therapeutic advances SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; AUTOIMMUNE-DISEASES; UNITED-STATES AB Systemic lupus erythematosus (SLE) is a severe autoimmune disease characterized by the presence of nucleic acid- and-protein-targeting autoantibodies and an aberrant type I IFN expression signature. Aicardi-Goutieres syndrome (AGS) is an autosomal-recessive encephalopathy in children that is characterized by mutations in numerous nucleic acid repair enzymes and elevated IFN levels. Phenotypically, patients with AGS and SLE share many similarities. Ribonuclease H2 (RNase H2) is a nucleic acid repair enzyme that removes unwanted ribonucleotides from DNA. In this issue of the JCI, Gunther and colleagues provide an in-depth investigation of the mechanisms underlying the link between defective removal of ribonucleotides in AGS and SLE, and these findings will likely serve as a strong springboard to provide novel therapeutic inroads. C1 [Pendergraft, William F., III] Univ N Carolina, Sch Med, Dept Med, Kidney Ctr,Div Nephrol & Hypertens, Chapel Hill, NC USA. [Pendergraft, William F., III; Means, Terry K.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Means, Terry K.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. [Means, Terry K.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. [Means, Terry K.] Harvard Univ, Sch Med, Charlestown, MA USA. RP Means, TK (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, 149 13th St Room 8407, Charlestown, MA 02129 USA. EM means.terry@mgh.harvard.edu FU NIAID NIH HHS [R01-AI084884, R01 AI084884]; NIDDK NIH HHS [1UM1-DK100845-01, UM1 DK100845, P01 DK058335, P01-DK058335-14] NR 14 TC 0 Z9 0 U1 1 U2 5 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2015 VL 125 IS 1 BP 102 EP 104 DI 10.1172/JCI78533 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AY7NS UT WOS:000347747300015 PM 25500879 ER PT J AU Gerriets, VA Kishton, RJ Nichols, AG Macintyre, AN Inoue, M Ilkayeva, O Winter, PS Liu, XJ Priyadharshini, B Slawinska, ME Haeberli, L Huck, C Turka, LA Wood, KC Hale, LP Smith, PA Schneider, MA MacIver, NJ Locasale, JW Newgard, CB Shinohara, ML Rathmell, JC AF Gerriets, Valerie A. Kishton, Rigel J. Nichols, Amanda G. Macintyre, Andrew N. Inoue, Makoto Ilkayeva, Olga Winter, Peter S. Liu, Xiaojing Priyadharshini, Bhavana Slawinska, Marta E. Haeberli, Lea Huck, Catherine Turka, Laurence A. Wood, Kris C. Hale, Laura P. Smith, Paul A. Schneider, Martin A. MacIver, Nancie J. Locasale, Jason W. Newgard, Christopher B. Shinohara, Mari L. Rathmell, Jeffrey C. TI Metabolic programming and PDHK1 control CD4(+) T cell subsets and inflammation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PYRUVATE-DEHYDROGENASE; GLUCOSE-METABOLISM; AUTOIMMUNE ENCEPHALOMYELITIS; INSULIN-RESISTANCE; OXIDATIVE STRESS; DICHLOROACETATE; DIFFERENTIATION; ACTIVATION; PATHWAY; CANCER AB Activation of CD4(+) T cells results in rapid proliferation and differentiation into effector and regulatory subsets. CD4(+) effector T cell (Teff) (Th1 and Th17) and Treg subsets are metabolically distinct, yet the specific metabolic differences that modify T cell populations are uncertain. Here, we evaluated CD4(+) T cell populations in murine models and determined thatinflammatory Teffs maintain high expression of glycolytic genes and rely on high glycolytic rates, while Tregs are oxidative and require mitochondrial electron transport to proliferate, differentiate, and survive. Metabolic profiling revealed that pyruvate dehydrogenase (PDH) is a key bifurcation point between T cell glycolytic and oxidative metabolism. PDH function is inhibited by PDH kinases (PDHKs). PDHK1 was expressed in Th17 cells, but not Th1 cells, and at low levels in Tregs, and inhibition or knockdown of PDHK1 selectively suppressed Th17 cells and increased Tregs. This alteration in the CD4+ T cell populations was mediated in part through ROS, as N-acetyl cysteine (NAC) treatment restored Th17 cell generation. Moreover, inhibition of PDHK1 modulated immunity and protected animals against experimental autoimmune encephalomyelitis, decreasing Th17 cells and increasing Tregs. Together, these data show that CD4(+) subsets utilize and require distinct metabolic programs that can be targeted to control specific T cell populations in autoimmune and inflammatory diseases. C1 [Gerriets, Valerie A.; Kishton, Rigel J.; Nichols, Amanda G.; Macintyre, Andrew N.; Winter, Peter S.; Wood, Kris C.; Newgard, Christopher B.; Rathmell, Jeffrey C.] Duke Univ, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. [Nichols, Amanda G.; Macintyre, Andrew N.; Inoue, Makoto; Shinohara, Mari L.; Rathmell, Jeffrey C.] Duke Univ, Dept Immunol, Durham, NC 27710 USA. [Nichols, Amanda G.; Macintyre, Andrew N.; Ilkayeva, Olga; Newgard, Christopher B.; Rathmell, Jeffrey C.] Duke Univ, Duke Mol Physiol Inst, Durham, NC 27710 USA. [Liu, Xiaojing; Locasale, Jason W.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. [Priyadharshini, Bhavana; Turka, Laurence A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Priyadharshini, Bhavana; Turka, Laurence A.] Harvard Univ, Sch Med, Boston, MA USA. [Slawinska, Marta E.; Haeberli, Lea; Huck, Catherine; Smith, Paul A.; Schneider, Martin A.] Novartis Inst Biomed Res Autoimmun Transplantat &, Basel, Switzerland. [Hale, Laura P.] Duke Univ, Dept Pathol, Durham, NC 27710 USA. [MacIver, Nancie J.] Duke Univ, Dept Pediat, Durham, NC 27710 USA. RP Rathmell, JC (reprint author), Duke Univ, Med Ctr, DUMC Box 3813, Durham, NC 27710 USA. EM jeff.rathmell@duke.edu OI Macintyre, Andrew/0000-0002-5297-0207; Locasale, Jason/0000-0002-7766-3502 FU Kenneth Rainin Foundation; Leukemia and Lymphoma Society; Crohn's and Colitis Foundation of America [284879]; Alliance for Lupus Research; National Multiple Sclerosis Society [RG4536-A-1]; NIH [R01HL108006, R56AI102074, R00CA168997, R01AI110613] FX We would like to acknowledge members of the Rathmell lab for support and helpful discussions and Marshall Nichols for technical assistance. This work was supported by grants from the Kenneth Rainin Foundation (to J.C. Rathmell), the Leukemia and Lymphoma Society (to J.C. Rathmell), the Crohn's and Colitis Foundation of America (Senior Research Award to J.C. Rathmell; postdoctoral fellowship 284879 to A.N. Macintyre), the Alliance for Lupus Research (Target Identification in Lupus to J.C. Rathmell), and the National Multiple Sclerosis Society (RG4536-A-1 to M.L. Shinohara)and by NIH grants R01HL108006 (to J.C. Rathmell), R56AI102074 (to J.C. Rathmell), R00CA168997 (to J.W. Locasale), and R01AI110613 (to J.W. Locasale). NR 46 TC 58 Z9 58 U1 5 U2 20 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2015 VL 125 IS 1 BP 194 EP 207 DI 10.1172/JCI76012 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AY7NS UT WOS:000347747300024 PM 25437876 ER PT J AU Menon, MC Chuang, PY Li, ZZ Wei, CG Zhang, WJ Luan, Y Yi, ZZ Xiong, HB Woytovich, C Greene, I Overbey, J Rosales, I Bagiella, E Chen, R Ma, M Li, L Ding, W Djamali, A Saminego, M O'Connell, PJ Gallon, L Colvin, R Schroppel, B He, JC Murphy, B AF Menon, Madhav C. Chuang, Peter Y. Li, Zhengzhe Wei, Chengguo Zhang, Weijia Luan, Yi Yi, Zhengzi Xiong, Huabao Woytovich, Christopher Greene, Ilana Overbey, Jessica Rosales, Ivy Bagiella, Emilia Chen, Rong Ma, Meng Li, Li Ding, Wei Djamali, Arjang Saminego, Millagros O'Connell, Philip J. Gallon, Lorenzo Colvin, Robert Schroppel, Bernd He, John Cijiang Murphy, Barbara TI Intronic locus determines SHROOM3 expression and potentiates renal allograft fibrosis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; LONG TERMINAL REPEAT; UNITED-STATES; EPITHELIAL-CELLS; BETA-CATENIN; TGF-BETA; TRANSCRIPTION; NEPHROPATHY; REJECTION AB Fibrosis underlies the loss of renal function in patients with chronic kidney disease (CID) and in kidney transplant recipients with chronic allograft nephropathy (CAN). Here, we studied the effect of an intronic SNP in SHROOM3, which has previously been linked to CI(D, on the development of CAN in a prospective cohort of renal allograft recipients. The presence of the rs17319721 allele at the SHROOM3 locus in the donor correlated with increased SHROOM3 expression in the allograft. In vitro, we determined that the sequence containing the risk allele at rs17319721 is a transcription factor 7-like-2-dependent (TCF7L2-dependent) enhancer element that functions to increase SHROOM3 transcription. In renal tubular cells, TGF-beta 1 administration upregulated SHROOM3 expression in a beta-catenin/TCF7L2-mediated manner, while SHROOM3 in turn facilitated canonical TGF-beta 1 signaling and increased alpha l collagen (COL1A1) expression. Inducible and tubular cell-specific knockdown of Shroom3 markedly abrogated interstitial fibrosis in mice with unilateral ureteric obstruction. Moreover, SHROOM3 expression in allografts at 3 months after transplant and the presence of the SHROOM3 risk allele in the donor correlated with increased allograft fibrosis and with reduced estimated glomerular filtration rate at 12 months after transplant. Our findings suggest that rs17319721 functions as a cis-acting expression quantitative trait locus of SHROOM3 that facilitates TGF-beta 1 signaling and contributes to allograft injury. C1 [Menon, Madhav C.; Chuang, Peter Y.; Li, Zhengzhe; Wei, Chengguo; Zhang, Weijia; Luan, Yi; Yi, Zhengzi; Woytovich, Christopher; Greene, Ilana; Overbey, Jessica; Bagiella, Emilia; Schroppel, Bernd; He, John Cijiang; Murphy, Barbara] Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, New York, NY 10029 USA. [Xiong, Huabao] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Rosales, Ivy; Colvin, Robert] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Chen, Rong; Ma, Meng; Li, Li; Ding, Wei] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Djamali, Arjang] Univ Wisconsin, Madison, WI USA. [Saminego, Millagros] Univ Michigan, Ann Arbor, MI 48109 USA. [O'Connell, Philip J.] Univ Sydney, Westmead Hosp, Renal Unit, Sydney, NSW 2006, Australia. [Gallon, Lorenzo] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [He, John Cijiang] James J Peter Vet Affairs Med Ctr, Renal Sect, New York, NY USA. RP Murphy, B (reprint author), Icahn Sch Med Mt Sinai, Dept Med, One Gustave L Levy Pl, New York, NY 10029 USA. EM Barbara.murphy@mssm.edu FU NIH [1U01AI070107, 1R01DK098126, 1R01DK078897, 1R01DK088541]; ASN Research Fellowship FX We thank Jeffrey Hildebrand for the rabbit anti-SHROOM3 antibody, the Shared Microscopy resource facility at Icahn School of Medicine at Mount Sinai, and Peter Heeger (Icahn School of Medicine at Mount Sinai) for critical reading and feedback. This work was supported by NIH grant 1U01AI070107 (to B. Murphy), an ASN Research Fellowship (to M.C. Menon), NIH grant 1R01DK098126 (to P.Y. Chuang), and NIH grants 1R01DK078897 and 1R01DK088541 (to J.C. He). NR 49 TC 10 Z9 10 U1 2 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2015 VL 125 IS 1 BP 208 EP 221 DI 10.1172/JCI76902 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AY7NS UT WOS:000347747300025 PM 25437874 ER PT J AU Fong, ZV Peev, M Warshaw, AL Lillemoe, KD Fernandez-del Castillo, C Velmahos, GC Fagenholz, PJ AF Fong, Zhi Ven Peev, Miroslav Warshaw, Andrew L. Lillemoe, Keith D. Fernandez-del Castillo, Carlos Velmahos, George C. Fagenholz, Peter J. TI Single-Stage Cholecystectomy at the Time of Pancreatic Necrosectomy Is Safe and Prevents Future Biliary Complications: a 20-Year Single Institutional Experience with 217 Consecutive Patients SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE Pancreatic necrosectomy; Single-stage cholecystectomy; Cholecystitis; Gallstone pancreatitis ID PERIPANCREATIC FLUID COLLECTIONS; GALLSTONE PANCREATITIS; INTRAOPERATIVE CHOLANGIOGRAPHY; LAPAROSCOPIC CHOLECYSTECTOMY; NECROTIZING PANCREATITIS; UNITED-STATES; MODERATE; EPIDEMIOLOGY; MORTALITY; CT AB Introduction Current guidelines recommend cholecystectomy (CCY) during the index admission for mild to moderate biliary pancreatitis as delayed CCY is associated with a substantial risk of recurrent biliary events. Delayed CCY is recommended in severe pancreatitis. The optimal timing of CCY in necrotizing pancreatitis, however, has not been well studied. We sought to determine the safety of single-stage CCYperformed at the time of necrosectomy and its effectiveness in preventing subsequent biliary complications. Methods We retrospectively queried our institutional database of patients who underwent pancreatic necrosectomy for necrotizing pancreatitis from 1992 to 2012. Results We identified 217 consecutive patients who underwent pancreatic necrosectomy during the study period. The most common etiologies of pancreatitis were biliary (41 %) and alcoholic (24 %), with a median computed tomography (CT) severity index score of 6 +/- 1.6 and a 63.6 % incidence of infected necrosis. Ninety-eight patients had undergone CCY prior to necrosectomy. Seventy patients (59 % of those with gallbladders in situ) underwent CCYat the time of pancreatic necrosectomy. CCY was not performed in the remaining 49 due to a clear non-biliary etiology (35 %), technical difficulty (29 %), intraoperative hemodynamic instability (18 %), or surgeon preference (18 %). Postoperative morbidity and mortality was no different between the CCYand no CCY groups, with no bile duct injury or bile leaks in patients undergoing CCYat the time of necrosectomy. Of the patients undergoing CCY, 43 % of patients without cholelithiasis or biliary sludge on preoperative imaging had gallstones or sludge identified pathologically after single-stage CCY. Of those who did not receive a single-stage CCY, biliary complications developed in 17 (35 %) of patients (21 % cholecystitis, 14 % recurrent gallstone pancreatitis) at a median time to incidence of 10 months. Seventeen (35%) patients eventually received a postnecrosectomy cholecystectomy, of which 75% required an open procedure. Conclusion Single-stage CCY at the time of pancreatic necrosectomy is safe in selected patients and should be performed if technically feasible to prevent future biliary complications and reduce the need for a subsequent separate, often open, CCY. C1 [Fong, Zhi Ven; Peev, Miroslav; Warshaw, Andrew L.; Lillemoe, Keith D.; Fernandez-del Castillo, Carlos; Velmahos, George C.; Fagenholz, Peter J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02163 USA. RP Fagenholz, PJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02163 USA. EM pfagenholz@mgh.harvard.edu NR 24 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X EI 1873-4626 J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD JAN PY 2015 VL 19 IS 1 BP 32 EP 38 DI 10.1007/s11605-014-2650-x PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA AY6NZ UT WOS:000347684100005 PM 25270594 ER PT J AU Sudan, R Nguyen, NT Hutter, MM Brethauer, SA Ponce, J Morton, JM AF Sudan, Ranjan Nguyen, Ninh T. Hutter, Matthew M. Brethauer, Stacy A. Ponce, Jaime Morton, John M. TI Morbidity, Mortality, and Weight Loss Outcomes After Reoperative Bariatric Surgery in the USA SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE Bariatric surgery; Gastric band; Gastric bypass; Biliopancreatic diversion with duodenal switch; Sleeve gastrectomy; Revision; Reoperation; Conversion ID Y GASTRIC BYPASS; DUODENAL SWITCH; LEARNING-CURVE; OPERATION; OBESITY AB Background Obesity is successfully treated by bariatric operations, but some patients need reoperations. No large national studies are available to evaluate the safety and efficacy after reoperative bariatric surgery. Methods Data from June 2007 throughMarch 2012 from the Bariatric Outcomes Longitudinal Database were queried for safety and efficacy of reoperations and compared to those who had initial bariatric operations but did not undergo reoperations. Reoperations were subdivided into corrective operations and conversions. Results Out of 449,753 bariatric operations, 28,720 (6.3 %) underwent reoperations of which 19,970 (69.5 %) were corrective and 8,750 (30.5 %) were conversions. The conversion group compared to primary operations was older (47.63 +/- 10.8 vs. 45.5 +/- 11.8 years), had less males (13.5 vs. 21.3%), and had more African Americans (14.6 vs. 12 %). Comparing primary operations to corrective and conversions operations, respectively, the following were observed: length of stay (1.78 +/- 4.95 vs. 2.04 6.44 and 2.86 +/- 4.58 days), severe adverse events at 30 days (1.6 vs. 1.7 and 3.3 %), severe adverse events at 1 year (2.15 vs. 1.9 and 3.61 %), percent excess weight loss at 1 year (43.2 vs. 35.9 +/- 92.4 and 39.3 +/- 39.9 %), 30-day mortality rate (0.1 vs. 0.12 and 0.21 %), and 1-year mortality rate (0.17 vs. 0.24 and 0.31 %). Comorbidities were resolved after both primary operations and reoperations. Conclusions Most bariatric surgery patients do not need reoperations. Among those who do, the complication rate is low and outcomes are clinically comparable to primary procedures. C1 [Sudan, Ranjan] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Nguyen, Ninh T.] Univ Calif Irvine, Irvine Med Ctr, Orange, CA 92668 USA. [Hutter, Matthew M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Brethauer, Stacy A.] Cleveland Clin, Cleveland, OH 44106 USA. [Ponce, Jaime] Hamilton Med Ctr, Dalton, GA USA. [Morton, John M.] Stanford Med Ctr, Palo Alto, CA USA. RP Sudan, R (reprint author), Duke Univ, Med Ctr, Dept Surg, Box 2834, Durham, NC 27710 USA. EM ranjan.sudan@duke.edu NR 19 TC 6 Z9 6 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X EI 1873-4626 J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD JAN PY 2015 VL 19 IS 1 BP 171 EP 179 DI 10.1007/s11605-014-2639-5 PG 9 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA AY6NZ UT WOS:000347684100021 PM 25186073 ER PT J AU Pugh, MJV Orman, JA Jaramillo, CA Salinsky, MC Eapen, BC Towne, AR Amuan, ME Roman, G McNamee, SD Kent, TA McMillan, KK Hamid, H Grafman, JH AF Pugh, Mary Jo V. Orman, Jean A. Jaramillo, Carlos A. Salinsky, Martin C. Eapen, Blessen C. Towne, Alan R. Amuan, Megan E. Roman, Gustavo McNamee, Shane D. Kent, Thomas A. McMillan, Katharine K. Hamid, Hamada Grafman, Jordan H. TI The Prevalence of Epilepsy and Association With Traumatic Brain Injury in Veterans of the Afghanistan and Iraq Wars SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article DE epidemiology; epilepsy; traumatic brain injury; Veterans ID ONSET UNPROVOKED SEIZURES; PENETRATING HEAD-INJURY; POSTTRAUMATIC EPILEPSY; BIDIRECTIONAL RELATION; ADMINISTRATIVE DATA; ANTIEPILEPTIC DRUG; CHRONIC PAIN; DISORDERS; COMORBIDITY; HYPERTENSION AB Objective: To examine the association of epilepsy with traumatic brain injury (TBI) in Afghanistan and Iraq (Operation Enduring Freedom [OEF]/Operation Iraqi Freedom [OIF]) Veterans. Design: Cross-sectional observational study. Participants: A total 256 284 OEF/OIF Veterans who received inpatient and outpatient care in the Veterans Health Administration in fiscal years 2009-2010. Main Outcome Measures: We used algorithms developed for use with International Classification of Diseases, Ninth Revision, Clinical Modification, codes to identify epilepsy, TBI (penetrating TBI [pTBI]/other TBI), and other risk factors for epilepsy (eg, stroke). TBI and other risk factors were identified prior to the index date (first date of seizure or October 1, 2009) for primary analyses. Results: Epilepsy prevalence was 10.6 per 1000 (N = 2719) in fiscal year 2010; age-adjusted prevalence was 6.1. Of 37 718 individuals with a diagnosis of TBI, 29 297 Veterans had a diagnosis of TBI prior to the index date. Statistically significant associations were found between epilepsy and prior TBI diagnosis (pTBI: adjusted odds ratio = 18.77 [95% confidence interval, 9.21-38.23]; other TBI: adjusted odds ratio = 1.64 [1.43-1.89]). Conclusions: Among OEF/OIF Veterans, epilepsy was associated with previous TBI diagnosis, with pTBI having the strongest association. Because war-related epilepsy in Vietnam War Veterans with TBI continued 35 years postwar, a detailed, prospective study is needed to understand the relationship between epilepsy and TBI severity in OEF/OIF Veterans. C1 [Pugh, Mary Jo V.; McMillan, Katharine K.] South Texas Vet Hlth Care Syst VERDICT, San Antonio, TX USA. [Pugh, Mary Jo V.; Orman, Jean A.; McMillan, Katharine K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Pugh, Mary Jo V.] Texas A&M Univ, Dept Med, Sch Med, College Stn, TX 77843 USA. [Orman, Jean A.] US Army Inst Surg Res, Houston, TX USA. [Orman, Jean A.] Univ Texas San Antonio, Sch Publ Hlth, San Antonio, TX USA. [Jaramillo, Carlos A.; Eapen, Blessen C.] UT Hlth Sci Ctr San Antonio, Dept Rehabil Med, Polytrauma Rehabil Ctr South Texas Vet Hlth Care, San Antonio, TX USA. [Salinsky, Martin C.] Portland VA Med Ctr, Portland, OR USA. [Salinsky, Martin C.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Towne, Alan R.] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Towne, Alan R.] McGuire Vet Adm Hosp, Epilepsy Ctr Excellence, Richmond, VA USA. [Amuan, Megan E.] Edith Nourse Rogers Mem Hosp, CHQOER, Bedford, MA USA. [Roman, Gustavo] Methodist Neurol Inst, Nantz Natl Alzheimer Ctr, Houston, TX USA. [McNamee, Shane D.] Hunter Holmes McGuire Vet Adm Hosp, Phys Med & Rehabil Serv, Richmond, VA USA. [Kent, Thomas A.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Kent, Thomas A.] Baylor Coll Med, Houston, TX 77030 USA. [Hamid, Hamada] West Haven VA Med Ctr, West Haven, CT USA. [Grafman, Jordan H.] Rehabil Inst Chicago, Chicago, IL 60611 USA. RP Pugh, MJV (reprint author), South Texas Vet Hlth Care Syst ALMD, 7400 Merton Minter Blvd 11C6, San Antonio, TX 78229 USA. EM pughm@uthscsa.edu OI Kent, Thomas/0000-0002-9877-7584; Grafman, Jordan H./0000-0001-8645-4457 FU VA Health Services Research and Development [DHI 09-237] FX The study was funded by VA Health Services Research and Development (DHI 09-237). Administrative, technical, or material support was provided by Kathleen Franklin, South Texas Veterans Healthcare System. Data analysis was conducted by Ms Amuan. NR 51 TC 8 Z9 8 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-9701 EI 1550-509X J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD JAN-FEB PY 2015 VL 30 IS 1 BP 29 EP 37 DI 10.1097/HTR.0000000000000045 PG 9 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA AY8BW UT WOS:000347780400012 PM 24695268 ER PT J AU Fortier, CB Amick, MM Kenna, A Milberg, WP McGlinchey, RE AF Fortier, Catherine Brawn Amick, Melissa M. Kenna, Alexandra Milberg, William P. McGlinchey, Regina E. TI Correspondence of the Boston Assessment of Traumatic Brain Injury-Lifetime (BAT-L) Clinical Interview and the VA TBI Screen SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article DE TBI; screen; Veteran; OEF/OIF ID ADMINISTERED PTSD SCALE; VETERANS AB Objective: Mild traumatic brain injury is the signature injury of Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), and Operation New Dawn (OND), yet its identification and diagnosis is controversial and fraught with challenges. Setting: In 2007, the Department of Veterans Affairs (VA) implemented a policy requiring traumatic brain injury (TBI) screening on all individuals returning from deployment in the OEF/OIF/OND theaters of operation that lead to the rapid and widespread use of the VA TBI screen. The Boston Assessment of TBI-Lifetime (BAT-L) is the first validated, postcombat semistructured clinical interview to characterize head injuries and diagnose TBIs throughout the life span, including prior to, during, and post-military service. Participants: Community-dwelling convenience sample of 179 OEF/OIF/OND veterans. Main measures: BAT-L, VA TBI screen. Results: Based on BAT-L diagnosis of military TBI, the VA TBI screen demonstrated similar sensitivity (0.85) and specificity (0.82) when administered by research staff. When BAT-L diagnosis was compared with historical clinician-administered VA TBI screen in a subset of participants, sensitivity was reduced. Conclusions: The specificity of the research-administered VA TBI screen was more than adequate. The sensitivity of the VA TBI screen, although relatively high, suggests that it does not oversample or "catch all" possible military TBIs. Traumatic brain injuries identified by the BAT-L, but not identified by the VA TBI screen, were predominantly noncombat military injuries. There is potential concern regarding the validity and reliability of the clinician administered VA TBI screen, as we found poor correspondence between it and the BAT-L, as well as low interrater reliability between the clinician-administered and research-administered screen. C1 [Fortier, Catherine Brawn; Amick, Melissa M.; Kenna, Alexandra; Milberg, William P.; McGlinchey, Regina E.] VA Boston Healthcare Syst, Translat Res Ctr TBI & Stress Disorders TRACTS, Boston, MA 02130 USA. [Fortier, Catherine Brawn; Milberg, William P.; McGlinchey, Regina E.] VA Boston Healthcare Syst, GRECC, Boston, MA 02130 USA. [Fortier, Catherine Brawn; Milberg, William P.; McGlinchey, Regina E.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Amick, Melissa M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Fortier, CB (reprint author), VA Boston Healthcare Syst, Translat Res Ctr TBI & Stress Disorders, Geriatr Res Educ & Clin Ctr JP 182, 150 South Huntington Ave, Boston, MA 02130 USA. EM Catherine_Fortier@hms.harvard.edu RI McGlinchey, Regina/R-1971-2016 FU Translational Research Center for TBI and Stress Disorders (TRACTS); VA Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence [B6796-C]; NIH NIA [K23AG034258]; VA Merit Review Award FX This research was supported by the Translational Research Center for TBI and Stress Disorders (TRACTS), a VA Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (B6796-C), NIH NIA K23AG034258, and VA Merit Review Award to Regina McGlinchey. NR 9 TC 5 Z9 5 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-9701 EI 1550-509X J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD JAN-FEB PY 2015 VL 30 IS 1 BP E1 EP E7 DI 10.1097/HTR.0000000000000008 PG 7 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA AY8BW UT WOS:000347780400001 PM 24336147 ER PT J AU Kearns, WD Fozard, JL Schonfeld, L Scott, S Marshall, K AF Kearns, William D. Fozard, James L. Schonfeld, Lawrence Scott, Steven Marshall, Katharine TI Elevated Movement Path Tortuosity in Voluntary Outdoor Ambulation in Community-Dwelling Veterans With a History of Traumatic Brain Injury SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article DE global positioning systems; (GPS); movement path tortuosity; outdoor ambulation; traumatic brain injury; veterans ID REHABILITATION; IMPAIRMENT; GAIT; VARIABILITY; PATTERNS; OUTCOMES; PROFILE; WALKING AB Objective: In comparison to veterans without a history of traumatic brain injury (TBI), we hypothesized that veterans with past TBI would have slower walking speed and more path tortuosity, TBI symptoms, problems with spatial orientation, and poorer executive function. Setting: Community nonclinical. Participants: Seventeen males (mean age of 37.2 years) reporting prior TBI and 20 non-TBI (mean age of 42.9 years). The number of years separating date of discharge and testing was 10.8 and 15.4 for the TBI and non-TBI groups, respectively. Design: Small 2 groups without random assignment. Main Measures: Brief Traumatic Brain Injury Screen, Trail Making Test-B, Clock Drawing Test, walking speed, and distance and path tortuosity in 30 minutes of voluntary outdoor walking wearing a small Global Positioning Systems recorder. Results: Those with TBI reported 4 Brief Traumatic Brain Injury Screen symptoms versus 0.4 for controls (F = 49.1; df = 1,35; P < .001) but did not differ on Trail Making Test-B or the Clock Drawing Test. Veterans with TBI walked shorter distances, 2.33 km versus 2.84 km (F = 4.8; df = 1,35; P < .05), and had greater path tortuosity (fractal D of 1.22 vs 1.15; F = 3.5; df = 1,35; P < .05) but did not differ on travel speed or time spent walking. Conclusions: Traumatic brain injury has persistent symptomatic effects and significantly affects ambulation and spatial orientation years after the event. These findings corroborate and extend observations linking cognitive impairment and ambulation. C1 [Kearns, William D.; Marshall, Katharine] Univ S Florida, Dept Rehabil & Mental Hlth Counseling, Tampa, FL 33612 USA. [Fozard, James L.] Univ S Florida, Sch Aging Studies, Tampa, FL 33612 USA. [Schonfeld, Lawrence] Univ S Florida, Florida Mental Hlth Inst, Tampa, FL 33612 USA. [Scott, Steven] James A Haley Vet Adm Hosp, Phys Med & Rehabil Serv, US Dept Vet Affairs, Tampa, FL USA. RP Kearns, WD (reprint author), Univ S Florida, Coll Behav & Community Sci, Dept Rehabil & Mental Hlth Counseling, 13301 B Downs Blvd,MHC1601 Tampa, Tampa, FL 33612 USA. EM Kearns@usf.edu RI Kearns, William/F-9810-2015 OI Kearns, William/0000-0002-0241-814X FU US Department of Defense [W81XWH-11-1-0634] FX This research was supported by the US Department of Defense under award number W81XWH-11-1-0634 to Dr Paul Sanberg "Battlefield-Related Injury Translational Research, Post-Traumatic Disease, and Disability Veterans Re-Integration." The authors also acknowledge Mr Charles Dion for his assistance with the statistical analysis. NR 28 TC 4 Z9 4 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-9701 EI 1550-509X J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD JAN-FEB PY 2015 VL 30 IS 1 BP E8 EP E14 DI 10.1097/HTR.0000000000000021 PG 7 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA AY8BW UT WOS:000347780400002 PM 24590148 ER PT J AU Salinsky, M Storzbach, D Goy, E Evrard, C AF Salinsky, Martin Storzbach, Daniel Goy, Elizabeth Evrard, Collette TI Traumatic Brain Injury and Psychogenic Seizures in Veterans SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article DE epilepsy; psychogenic seizures; PTSD; TBI; Veterans ID POSTTRAUMATIC-STRESS-DISORDER; NONEPILEPTIC SEIZURES; VIDEO-EEG; EPILEPSY; HEALTH; IRAQ; COMORBIDITY; SYMPTOMS; SEQUELAE; OUTCOMES AB Objective: To evaluate a proposed seizure etiology of traumatic brain injury (TBI) as a risk factor for psychogenic nonepileptic seizures (PNESs), the effect of reported TBI severity on the diagnosis of PNES versus epileptic seizures (ESs), and the potential moderating role of posttraumatic stress disorder (PTSD). Participants, Setting: Veterans with a diagnosis of PNES or ES during epilepsy monitoring at a Veterans Affairs Medical Center. Design: Retrospective review of seizure type, proposed seizure etiology, TBI severity, and PTSD. Main Outcomes: Both PNES and ES groups were compared for TBI history and severity, and prior diagnosis of PTSD. Results: Traumatic brain injury was the proposed seizure etiology for 57% of 67 PNES patients versus 35% of 54 ES patients (P < .05). It was mild in 87% of PNES patients and 37% of ES patients (P < .001). Posttraumatic stress disorder increased the likelihood of diagnosing PNES versus ES in Veterans with mild TBI as the proposed seizure etiology. Conclusions: Veterans with PNES commonly cite a TBI as the cause for seizures. Mild TBI was strongly associated with PNES versus ES. Posttraumatic stress disorder may moderate the development of PNES in Veterans with a history of mild TBI. Clinicians caring for Veterans with seizures may use these results in selecting patients for early diagnostic evaluation. C1 [Salinsky, Martin; Storzbach, Daniel; Goy, Elizabeth; Evrard, Collette] Portland VA Med Ctr, Portland, OR USA. [Salinsky, Martin] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Salinsky, M (reprint author), Portland VAMC Epilepsy Ctr, 3710 SWUS Vet Hosp Rd P3ECOE, Portland, OR 97239 USA. EM Salinsky@ohsu.edu NR 38 TC 5 Z9 5 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-9701 EI 1550-509X J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD JAN-FEB PY 2015 VL 30 IS 1 BP E65 EP E70 DI 10.1097/HTR.0000000000000057 PG 6 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA AY8BW UT WOS:000347780400008 PM 24901325 ER PT J AU Kasckow, J Yeager, DE Magruder, K AF Kasckow, John Yeager, Derik E. Magruder, Kathryn TI Levels of Symptom Severity and Functioning in Four Different Definitions of Subthreshold Posttraumatic Stress Disorder in Primary Care Veterans SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Posttraumatic stress disorder; subthreshold; functioning; posttraumatic checklist score ID NATIONAL EPIDEMIOLOGIC SURVEY; SF-36 HEALTH SURVEY; IQOLA PROJECT; PTSD SYMPTOMS; WAVE 2; FULL; COMORBIDITY; PREVALENCE; PREDICTORS; VICTIMS AB Four definitions of subthreshold posttraumatic stress disorder (PTSD) were compared in 815 veterans seen in Veterans Affairs Medical Center primary care clinics. We compared PTSD Checklist (PCL) scores and Short Form 36 (SF-36) scores between participants meeting criteria for one of the subthreshold PTSD definitions (based on Schnurr, Marshall, Blanchard, or Stein) to those with and without PTSD. Using regression, thosemeeting subthreshold criteria by any of the four definitions had lower mental and physical health functioning and higher PCL scores relative to those without PTSD; they also had higher mental health functioning and lower PCL scores relative to those with PTSD. With SF-36 physical functioning scores, only those meeting the Stein definition differed from the group with PTSD. Thus, these definitions appear to distinguish individuals who are qualitatively different from individuals with no PTSD or with PTSD and are nearly equivalent in their ability to discriminate individuals. C1 [Kasckow, John] Vet Affairs Pittsburgh Hlth Care Syst, Pittsburgh, PA 15420 USA. [Kasckow, John] Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15260 USA. [Yeager, Derik E.; Magruder, Kathryn] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Yeager, Derik E.; Magruder, Kathryn] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA. RP Kasckow, J (reprint author), Vet Affairs Pittsburgh Hlth Care Syst, Univ Dr C, Pittsburgh, PA 15420 USA. EM kasckowjw@upmc.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development [VCR 99-010-2] FX This material is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development: VCR 99-010-2. NR 29 TC 3 Z9 3 U1 4 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JAN PY 2015 VL 203 IS 1 BP 43 EP 47 DI 10.1097/NMD.0000000000000233 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AY5TM UT WOS:000347634600009 PM 25503958 ER PT J AU Lu, L Saha, D Martuza, RL Rabkin, SD Wakimoto, H AF Lu, Lei Saha, Dipongkor Martuza, Robert L. Rabkin, Samuel D. Wakimoto, Hiroaki TI Single agent efficacy of the VEGFR kinase inhibitor axitinib in preclinical models of glioblastoma SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Glioblastoma; Axitinib; Anti-angiogenic therapy; Glioblastoma stem cells; Molecular targeted therapy ID NEWLY-DIAGNOSED GLIOBLASTOMA; BEVACIZUMAB PLUS IRINOTECAN; STEM-LIKE CELLS; PHASE-II; RECURRENT GLIOBLASTOMA; ADJUVANT TEMOZOLOMIDE; ANTITUMOR-ACTIVITY; RANDOMIZED-TRIAL; DENDRITIC CELLS; TUMOR-GROWTH AB Anti-angiogenic therapy is a promising therapeutic strategy for the highly vascular and malignant brain tumor, glioblastoma (GBM), although current clinical trials have failed to demonstrate an extension in overall survival. The small molecule tyrosine kinase inhibitor axitinib that targets vascular endothelial growth factor receptor, potently inhibits angiogenesis and has single-agent clinical activity in non-small cell lung, thyroid, and advanced renal cell cancer. Here we show that axitinib exerts direct cytotoxic activity against a number of patient-derived GBM stem cell (GSCs) and an endothelial cell line, and inhibits endothelial tube formation in vitro. Axitinib treatment of mice bearing hypervascular intracranial tumors generated from human U87 glioma cells, MGG4 GSCs and mouse 005 GSCs significantly extended survival that was associated with decreases in tumor-associated vascularity. We thus show for the first time the antiangiogenic effect and survival prolongation provided by systemic single agent treatment with axitinib in preclinical orthotopic GBM models including clinically relevant GSC models. These results support further investigation of axitinib as an anti-angiogenic agent for GBM. C1 [Lu, Lei; Saha, Dipongkor; Martuza, Robert L.; Rabkin, Samuel D.; Wakimoto, Hiroaki] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. [Lu, Lei] Fudan Univ, Dept Neurosurg, Huashan Hosp, Shanghai 200040, Peoples R China. RP Wakimoto, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. EM hwakimoto@mgh.harvard.edu OI rabkin, samuel/0000-0003-2344-2795 FU National Institute of Health [R01NS032677] FX We thank Pfizer for providing axitinib, Drs. Giulia Fulci, Brent J. Passer, and David J. Waxman for technical advice, and Melissa R. Marinelli, Andrea Murphy, Tooba Cheema, and Shinichi Esaki for their experimental help. This work was supported by a grant from the National Institute of Health (Grant number R01NS032677). NR 46 TC 7 Z9 8 U1 3 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD JAN PY 2015 VL 121 IS 1 BP 91 EP 100 DI 10.1007/s11060-014-1612-1 PG 10 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA AY9UE UT WOS:000347895100009 PM 25213669 ER PT J AU Tache, Y Million, M AF Tache, Yvette Million, Mulugeta TI Role of Corticotropin-releasing Factor Signaling in Stress-related Alterations of Colonic Motility and Hyperalgesia SO JOURNAL OF NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE Colonic motility; Corticotropin-releasing factor; Irritable bowel syndrome; Stress; Visceral pain ID IRRITABLE-BOWEL-SYNDROME; BRAIN-GUT AXIS; FACTOR CRF FAMILY; INDUCED VISCERAL HYPERALGESIA; RECEPTOR-MEDIATED MECHANISMS; WATER-AVOIDANCE STRESS; ENTERIC NERVOUS-SYSTEM; MUCOSAL BARRIER FUNCTION; LOCUS-COERULEUS NEURONS; HORMONE TYPE-1 RECEPTOR AB The corticotropin-releasing factor (CRF) signaling systems encompass CRF and the structurally related peptide urocortin (Ucn) 1, 2, and 3 along with 2 G-protein coupled receptors, CRF1 and CRF2. CRF binds with high and moderate affinity to CRF1 and CRF2 receptors, respectively while Ucn1 is a high-affinity agonist at both receptors, and Ucn2 and Ucn3 are selective CRF2 agonists. The CRF systems are expressed in both the brain and the colon at the gene and protein levels. Experimental studies established that the activation of CRF1 pathway in the brain or the colon recaptures cardinal features of diarrhea predominant irritable bowel syndrome (IBS) (stimulation of colonic motility, activation of mast cells and serotonin, defecation/watery diarrhea, and visceral hyperalgesia). Conversely, selective CRF1 antagonists or CRF1/CRF2 antagonists, abolished or reduced exogenous CRF and stress-induced stimulation of colonic motility, defecation, diarrhea and colonic mast cell activation and visceral hyperalgesia to colorectal distention. By contrast, the CRF2 signaling in the colon dampened the CRF1 mediated stimulation of colonic motor function and visceral hyperalgesia. These data provide a conceptual framework that sustained activation of the CRF1 system at central and/or peripheral sites may be one of the underlying basis of IBS-diarrhea symptoms. While targeting these mechanisms by CRF1 antagonists provided a relevant novel therapeutic venue, so far these promising preclinical data have not translated into therapeutic use of CRF1 antagonists. Whether the existing or newly developed CRF1 antagonists will progress to therapeutic benefits for stress-sensitive diseases including IBS for a subset of patients is still a work in progress. C1 Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Ctr Neurobiol Stress, Div Digest Dis, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Tache, Y (reprint author), VA Greater Los Angeles Healthcare Syst, Ctr Neurovisceral Sci & Womens Hlth, CURE Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU NIHDDK [R01 DK-33061, R01 DK-57236, R01 DK-078676, DK-41301, P50 AR-049550]; VA Merit and Senior Scientist Awards FX This work was supported by the NIHDDK grants R01 DK-33061 (YT), R01 DK-57236 (YT), R01 DK-078676 (MM), DK-41301 (Animal Models Core, YT, MM), P50 AR-049550 (YT, MM), and VA Merit and Senior Scientist Awards (YT). NR 210 TC 19 Z9 20 U1 2 U2 15 PU KOREAN SOC NEUROGASTROENTEROLOGY & MOTILITY PI GANGNAM-GU PA RM 305, LOTTE GOLD ROSE VILL II, 31 SEOLLEUNG-RO 86-GIL, GANGNAM-GU, SEOUL 135-839, SOUTH KOREA SN 2093-0879 EI 2093-0887 J9 J NEUROGASTROENTEROL JI J. Neurogastroenterol. Motil. PD JAN PY 2015 VL 21 IS 1 BP 8 EP 24 DI 10.5056/jnm14162 PG 17 WC Gastroenterology & Hepatology; Clinical Neurology SC Gastroenterology & Hepatology; Neurosciences & Neurology GA AY7JI UT WOS:000347736300003 PM 25611064 ER PT J AU Klawiter, EC Ceccarelli, A Arora, A Jackson, J Bakshi, S Kim, G Miller, J Tauhid, S von Gizycki, C Bakshi, R Neema, M AF Klawiter, Eric C. Ceccarelli, Antonia Arora, Ashish Jackson, Jonathan Bakshi, Sonya Kim, Gloria Miller, Jennifer Tauhid, Shahamat von Gizycki, Christian Bakshi, Rohit Neema, Mohit TI Corpus Callosum Atrophy Correlates with Gray Matter Atrophy in Patients with Multiple Sclerosis SO JOURNAL OF NEUROIMAGING LA English DT Article DE Multiple sclerosis; corpus callosum; atrophy ID BRAIN ATROPHY; DYSFUNCTION; IMPAIRMENT; MRI; 3T AB OBJECTIVE Atrophy of the corpus callosum is a recognized characteristic of multiple sclerosis (MS). We describe a new reliable method for measuring corpus callosum atrophy and correlate this with global cerebral atrophy measures. METHODS Whole brain 3T MRI was performed in 38 relapsing-remitting MS subjects and 21 healthy controls (HC). Brain global gray and white matter volumes were segmented with SPM8. The contour of the corpus callosum was outlined on the midline of 3-D T1-weighted images by a semiautomated edge-detection technique to determine the corpus callosum area (CCA). Normalized CCA was correlated with other brain atrophy measures in MS subjects. RESULTS CCA was disproportionately lower in MS subjects vs. HC (20.1% mean decrease; P < .001), with a large effect size (d = .62) when compared with global atrophy measures. In MS subjects, CCA correlated with brain parenchymal fraction (r = .55; P < .001) and gray matter fraction (r = .45; P = .005) but not white matter fraction (r = .18; P = .29). An inverse correlation with FLAIR hyperintense lesion volume (r = -.40; P = .01) was detected for CCA. CONCLUSION Measurement of atrophy of the corpus callosum can have sensitivity as a useful imaging biomarker in patients with MS, even in patients with low disability levels. Both gray and white matter involvement in MS contribute to corpus callosum atrophy. C1 [Klawiter, Eric C.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Ceccarelli, Antonia; Arora, Ashish; Jackson, Jonathan; Bakshi, Sonya; Kim, Gloria; Miller, Jennifer; Tauhid, Shahamat; von Gizycki, Christian; Bakshi, Rohit; Neema, Mohit] Harvard Univ, Sch Med, Dept Neurol, Brigham & Womens Hosp,Lab Neuroimaging Res,Partne, Boston, MA 02115 USA. RP Neema, M (reprint author), Brigham & Womens Hosp, Suite 602,1 Brookline, Brookline, MA 02445 USA. EM mneema@bwh.harvard.edu FU National Institutes of Health [1K23NS078044-01]; National Multiple Sclerosis Society [RG3798A2] FX Supported by grants from the National Institutes of Health (1K23NS078044-01 [ECK]) and the National Multiple Sclerosis Society (RG3798A2, RB). NR 32 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1051-2284 EI 1552-6569 J9 J NEUROIMAGING JI J. Neuroimaging PD JAN-FEB PY 2015 VL 25 IS 1 BP 62 EP 67 DI 10.1111/jon.12124 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AY6ZX UT WOS:000347712100006 PM 24816394 ER PT J AU Abujudeh, HH AF Abujudeh, Hani H. TI "Just Culture": Is Radiology Ready? SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Abujudeh, HH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St,Founders 213B, Boston, MA 02114 USA. EM habujudeh@partners.org NR 3 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JAN PY 2015 VL 12 IS 1 BP 4 EP 5 DI 10.1016/j.jacr.2014.02.010 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AY7NT UT WOS:000347747400003 PM 24731503 ER PT J AU Lam, DL McNeeley, MF Bhargava, P AF Lam, Diana L. McNeeley, Michael F. Bhargava, Puneet TI Lessons From the Happiest Place on Earth SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Lam, Diana L.; McNeeley, Michael F.] Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA. [Bhargava, Puneet] Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Diagnost Imaging Serv, Seattle, WA USA. [Bhargava, Puneet] Univ Washington, Seattle, WA 98108 USA. RP Lam, DL (reprint author), Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA. EM bhargp@uw.edu OI Bhargava, Puneet/0000-0002-3849-9666 NR 13 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JAN PY 2015 VL 12 IS 1 BP 6 EP 8 DI 10.1016/j.jacr.2014.02.014 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AY7NT UT WOS:000347747400004 PM 24713503 ER PT J AU Boland, GW Thrall, JH Duszak, R AF Boland, Giles W. Thrall, James H. Duszak, Richard, Jr. TI Business Intelligence, Data Mining, and Future Trends SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material ID HEALTH-CARE C1 [Boland, Giles W.; Thrall, James H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Duszak, Richard, Jr.] Emory Univ, Sch Med, Dept Radiol & Imaging Sci, Atlanta, GA 30322 USA. RP Boland, GW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. EM gboland@partners.org RI Duszak, Richard/L-1811-2016 OI Duszak, Richard/0000-0003-0425-3008 NR 6 TC 3 Z9 3 U1 1 U2 24 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JAN PY 2015 VL 12 IS 1 BP 9 EP 11 DI 10.1016/j.jacr.2014.10.003 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AY7NT UT WOS:000347747400005 PM 25557564 ER PT J AU Remedios, D Brink, J Holmberg, O Kawooya, M Med, M Mendelson, R Naidoo, A Reed, M Bettmann, M AF Remedios, Denis Brink, James Holmberg, Ola Kawooya, Michael Med, M. Mendelson, Richard Naidoo, Anusha Reed, Martin Bettmann, Michael CA Behalf Members IAEA Tech Meetings TI Clinical Imaging Guidelines Part 1: A Proposal for Uniform Methodology SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Imaging; guidelines; justification; appropriateness ID RECOMMENDATIONS; STRENGTH; QUALITY; GRADE AB Inappropriate imaging can lead to unnecessary medical radiologic exposures and cost and may not answer the clinical question. Imaging referral guidelines inform the justification of radiologic procedures and facilitate the choice of the best test first, but their acceptance by referrers, use, and value may be limited by shortcomings in the methodology of development. Focusing on common, essential elements of methodology will help guideline developers. In 2012 and 2013, the International Atomic Energy Agency hosted Technical Meetings on Radiation Protection of Patients Through the Development of Appropriateness Criteria in Diagnostic Imaging. Participants identified and agreed on issues concerning development of imaging referral guidelines. Items based on the Appraisal of Guidelines for Research and Evaluation II instrument were amended with additional items including development and consensus group composition. Consensus was sought on 28 items, 18 of which were agreed should be uniform, and 10 should allow for regional differences. Further work is required to encourage, provide, and identify higher quality evidence and to agree on a grading system for recommendations. Many key areas are common to guideline developers globally, opening the way for international collaboration to help demystify, simplify, and justify. C1 [Remedios, Denis] Northwick Pk Hosp & Clin Res Ctr, Dept Clin Radiol, Harrow HA1 3UJ, Middx, England. [Brink, James] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Holmberg, Ola] IAEA, Div Radiat, Div Radiat Transport & Waste Safety, A-1400 Vienna, Austria. [Med, M.] Mengo Hosp, Ernest Cook Ultrasound Res & Educ Inst, Dept Radiol, Kampala, Uganda. [Mendelson, Richard] Royal Perth Hosp, Dept Radiol, Perth, WA 6001, Australia. [Naidoo, Anusha] Future Med Imaging Grp, Melbourne, Vic, Australia. [Reed, Martin] Winnipeg Childrens Hosp, Dept Diagnost Imaging, Winnipeg, MB, Canada. [Bettmann, Michael] Wake Forest Univ, Dept Radiol, Winston Salem, NC 27109 USA. RP Remedios, D (reprint author), Northwick Pk Hosp & Clin Res Ctr, Dept Clin Radiol, Harrow HA1 3UJ, Middx, England. EM denis.remedios@imperial.ac.uk NR 18 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JAN PY 2015 VL 12 IS 1 BP 45 EP 50 DI 10.1016/j.jacr.2014.07.023 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AY7NT UT WOS:000347747400015 PM 25441484 ER PT J AU Liapi, E Mahesh, M Sahani, DV AF Liapi, Eleni Mahesh, Mahadevappa Sahani, Dushyant V. TI Is CT Perfusion Ready for Liver Cancer Treatment Evaluation? SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Liapi, Eleni; Mahesh, Mahadevappa] Johns Hopkins Univ, Sch Med, Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA. [Sahani, Dushyant V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mahesh, M (reprint author), Johns Hopkins Univ, 601 N Caroline St, Baltimore, MD 21287 USA. EM mmahesh@jhmi.edu NR 9 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JAN PY 2015 VL 12 IS 1 BP 111 EP 113 DI 10.1016/j.jacr.2014.10.007 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AY7NT UT WOS:000347747400028 PM 25557575 ER PT J AU Wood, DE Kazerooni, E Baum, SL Dransfield, MT Eapen, GA Ettinger, DS Hou, L Jackman, DM Klippenstein, D Kumar, R Lackner, RP Leard, LE Leung, ANC Makani, SS Massion, PP Meyers, BF Otterson, GA Peairs, K Pipavath, S Pratt-Pozo, C Reddy, C Reid, ME Rotter, AJ Sachs, PB Schabath, MB Sequist, LV Tong, BC Travis, WD Yang, SC Gregory, KM Hughes, M AF Wood, Douglas E. Kazerooni, Ella Baum, Scott L. Dransfield, Mark T. Eapen, George A. Ettinger, David S. Hou, Lifang Jackman, David M. Klippenstein, Donald Kumar, Rohit Lackner, Rudy P. Leard, Lorriana E. Leung, Ann N. C. Makani, Samir S. Massion, Pierre P. Meyers, Bryan F. Otterson, Gregory A. Peairs, Kimberly Pipavath, Sudhakar Pratt-Pozo, Christie Reddy, Chakravarthy Reid, Mary E. Rotter, Arnold J. Sachs, Peter B. Schabath, Matthew B. Sequist, Lecia V. Tong, Betty C. Travis, William D. Yang, Stephen C. Gregory, Kristina M. Hughes, Miranda TI Lung Cancer Screening, Version 1.2015 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID MAXIMUM INTENSITY PROJECTION; CLINICAL-PRACTICE GUIDELINES; COMPUTER-AIDED DETECTION; ED AMERICAN-COLLEGE; LOW-DOSE CT; GROUND-GLASS OPACITY; SOLITARY PULMONARY NODULE; POSITIVE TEST RESULT; SERVICES TASK-FORCE; UNITED-STATES AB The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Lung Cancer Screening provide recommendations for selecting individuals for lung cancer screening, and for evaluation and follow-up of nodules found during screening, and are intended to assist with clinical and shared decision-making. These NCCN Guidelines Insights focus on the major updates to the 2015 NCCN Guidelines for Lung Cancer Screening, which include a revision to the recommendation from category 2B to 2A for one of the high-risk groups eligible for lung cancer screening. For low-dose CT of the lung, the recommended slice width was revised in the table on "Low-Dose Computed Tomography Acquisition, Storage, Interpretation, and Nodule Reporting." C1 [Wood, Douglas E.; Hou, Lifang; Leung, Ann N. C.; Pipavath, Sudhakar; Hughes, Miranda] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Sequist, Lecia V.; Tong, Betty C.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Schabath, Matthew B.] Univ Tennessee, St Jude Childrens Res Hosp, Hlth Sci Ctr, Knoxville, TN 37996 USA. [Rotter, Arnold J.] Univ Alabama, Birmingham Comprehens Canc Ctr, Tuscaloosa, AL 35487 USA. [Reid, Mary E.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Reid, Mary E.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Pratt-Pozo, Christie] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Pratt-Pozo, Christie] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Peairs, Kimberly] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Otterson, Gregory A.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Meyers, Bryan F.] Nebraska Med Ctr, Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Massion, Pierre P.] UCSF, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Massion, Pierre P.] Stanford Comprehens Canc Ctr, Palo Alto, CA USA. [Makani, Samir S.] UC San Diego Moores Canc Ctr, San Diego, CA USA. [Leung, Ann N. C.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Leard, Lorriana E.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Lackner, Rudy P.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Kumar, Rohit] Ohio State Univ, James Canc Hosp, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Klippenstein, Donald] Solove Res Inst, Columbus, OH USA. [Hou, Lifang] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Eapen, George A.] Roswell Pk Canc Inst, Buffalo, NY USA. [Sachs, Peter B.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Schabath, Matthew B.] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Sequist, Lecia V.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Travis, William D.] Duke Canc Inst, Raleigh, NC USA. [Yang, Stephen C.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Yang, Stephen C.] Natl Comprehens Canc Network, Ft Washington, MD USA. RP Wood, DE (reprint author), Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. RI Schabath, Matthew/J-3763-2016 OI Schabath, Matthew/0000-0003-3241-3216 NR 124 TC 19 Z9 24 U1 1 U2 13 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JAN PY 2015 VL 13 IS 1 BP 23 EP 34 PG 12 WC Oncology SC Oncology GA AY8GU UT WOS:000347793200007 PM 25583767 ER PT J AU Aizer, AA Gu, X Chen, MH Choueiri, TK Martin, NE Efstathiou, JA Hyatt, AS Graham, PL Trinh, QD Hu, JC Nguyen, PL AF Aizer, Ayal A. Gu, Xiangmei Chen, Ming-Hui Choueiri, Toni K. Martin, Neil E. Efstathiou, Jason A. Hyatt, Andrew S. Graham, Powell L. Trinh, Quoc-Dien Hu, Jim C. Nguyen, Paul L. TI Cost Implications and Complications of Overtreatment of Low-Risk Prostate Cancer in the United States SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID ACTIVE SURVEILLANCE; RADICAL PROSTATECTOMY; RADIATION ONCOLOGY; ADMINISTRATIVE DATA; NEEDLE BIOPSIES; MEN; CARE; OUTCOMES; THERAPY; TECHNOLOGIES AB Background: Evidence-based consensus guidelines recommend only observation for men with low-risk prostate cancer and life expectancy less than 10 years. This report describes the incidence, drivers, cost, and morbidity of overtreatment of low-risk prostate cancer within the United States. Methods: The SEER-Medicare Program was used to identify 11,744 men aged 66 years or older diagnosed with low-risk prostate cancer in 2004 through 2007. Overtreatment of prostate cancer was defined as definitive treatment of a patient with a life expectancy of less than 10 years. Expected survival was estimated using NCCN methodology. Costs were the amount paid by Medicare in years after minus year before diagnosis. Toxicities were relevant Medicare diagnoses/interventions. P values are 2-sided. Results: Of 3001 men with low-risk prostate cancer and a life expectancy of less than 10 years, 2011 men (67%) were overtreated. On multivariable logistic regression, overtreated men were more likely to be married (odds ratio [OR], 1.29; 95% CI, 1.05-1.59; P=.02), reside in affluent regions (P<.001), and harbor more advanced disease at diagnosis (P<.001). Two-year toxicity was greater in overtreated patients (P<.001). Relative to active surveillance/watchful waiting/observation, the median additional cost per definitive treatment was $18,827 over 5 years; the cumulative annual cost attributable to overtreatment in the United States was $58.7 million. The ability to avoid treating the 80% of men with low-grade disease who will never die of prostate cancer would save $1.32 billion per year nationally. Conclusions: Overtreatment of low-risk prostate cancer is partially driven by sociodemographic factors and occurs frequently, with marked impact on patient quality of life and health-related costs. C1 [Aizer, Ayal A.] Harvard Radiat Oncol Program, Boston, MA USA. [Gu, Xiangmei] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Choueiri, Toni K.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Martin, Neil E.; Hyatt, Andrew S.; Graham, Powell L.; Nguyen, Paul L.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Efstathiou, Jason A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Trinh, Quoc-Dien] Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. [Hu, Jim C.] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA. RP Nguyen, PL (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM pnguyen@lroc.harvard.edu RI Martin, Neil/E-2193-2014 OI Martin, Neil/0000-0002-8164-8516 NR 49 TC 15 Z9 15 U1 0 U2 4 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JAN PY 2015 VL 13 IS 1 BP 61 EP 68 PG 8 WC Oncology SC Oncology GA AY8GU UT WOS:000347793200010 PM 25583770 ER PT J AU Kulke, MH Shah, MH Benson, AB Bergsland, E Berlin, JD Blaszkowsky, LS Emerson, L Engstrom, PF Fanta, P Giordano, T Goldner, WS Halfdanarson, TR Heslin, MJ Kandeel, F Kunz, PL Kuvshinoff, BV Lieu, C Moley, JF Munene, G Pillarisetty, VG Saltz, L Sosa, JA Strosberg, JR Vauthey, JN Wolfgang, C Yao, JC Burns, J Freedman-Cass, D AF Kulke, Matthew H. Shah, Manisha H. Benson, Al B., III Bergsland, Emily Berlin, Jordan D. Blaszkowsky, Lawrence S. Emerson, Lyska Engstrom, Paul F. Fanta, Paul Giordano, Thomas Goldner, Whitney S. Halfdanarson, Thorvardur R. Heslin, Martin J. Kandeel, Fouad Kunz, Pamela L. Kuvshinoff, Boris W., II Lieu, Christopher Moley, Jeffery F. Munene, Gitonga Pillarisetty, Venu G. Saltz, Leonard Sosa, Julie Ann Strosberg, Jonathan R. Vauthey, Jean-Nicolas Wolfgang, Christopher Yao, James C. Burns, Jennifer Freedman-Cass, Deborah TI Neuroendocrine Tumors, Version 1.2015 SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID RADIOLABELED SOMATOSTATIN ANALOG; PANCREATIC ENDOCRINE TUMORS; HEPATIC ARTERIAL CHEMOEMBOLIZATION; LAPAROSCOPIC THERMAL ABLATION; PROLONGED-RELEASE LANREOTIDE; MALIGNANT CARCINOID-SYNDROME; TREATMENT-RELATED MORTALITY; ISLET-CELL CARCINOMA; LONG-TERM SURVIVAL; LIVER-TRANSPLANTATION AB Neuroendocrine tumors (NETs) comprise a broad family of tumors that may or may not be associated with symptoms attributable to hormonal hypersecretion. The NCCN Clinical Practice Guidelines in Oncology for Neuroendocrine Tumors discuss the diagnosis and management of both sporadic and hereditary NETs. This selection from the guidelines focuses on sporadic NETs of the pancreas, gastrointestinal tract, lung, and thymus. C1 [Kulke, Matthew H.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02215 USA. [Shah, Manisha H.] Ohio State Univ, James Canc Hosp, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Shah, Manisha H.] Solove Res Inst, Columbus, OH USA. [Benson, Al B., III] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Bergsland, Emily] UCSF, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Berlin, Jordan D.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Blaszkowsky, Lawrence S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Emerson, Lyska] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Engstrom, Paul F.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Fanta, Paul] UC San Diego Moores Canc Ctr, San Diego, CA USA. [Giordano, Thomas] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Goldner, Whitney S.] Nebraska Med Ctr, Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Halfdanarson, Thorvardur R.] Mayo Clin, Ctr Canc, Rochester, MN USA. [Heslin, Martin J.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Kandeel, Fouad] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Kunz, Pamela L.] Stanford Canc Inst, Stanford, CA USA. [Kuvshinoff, Boris W., II] Roswell Pk Canc Inst, Buffalo, NY USA. [Lieu, Christopher] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Moley, Jeffery F.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Moley, Jeffery F.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Munene, Gitonga] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Pillarisetty, Venu G.] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Saltz, Leonard] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Sosa, Julie Ann] Duke Canc Inst, Raleigh, NC USA. [Strosberg, Jonathan R.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Vauthey, Jean-Nicolas; Yao, James C.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Wolfgang, Christopher] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. RP Kulke, MH (reprint author), Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02215 USA. OI Saltz, Leonard/0000-0001-8353-4670 NR 161 TC 57 Z9 63 U1 3 U2 18 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JAN PY 2015 VL 13 IS 1 BP 78 EP 108 PG 31 WC Oncology SC Oncology GA AY8GU UT WOS:000347793200012 PM 25583772 ER PT J AU Weisberg, E Nonami, A Chen, Z Liu, F Zhang, J Sattler, M Nelson, E Cowens, K Christie, AL Mitsiades, C Wong, KK Liu, Q Gray, N Griffin, JD AF Weisberg, E. Nonami, A. Chen, Z. Liu, F. Zhang, J. Sattler, M. Nelson, E. Cowens, K. Christie, A. L. Mitsiades, C. Wong, K-K Liu, Q. Gray, N. Griffin, J. D. TI Identification of Weel as a novel therapeutic target for mutant RAS-driven acute leukemia and other malignancies SO LEUKEMIA LA English DT Article ID ANTITUMOR-ACTIVITY; MITOTIC CATASTROPHE; PRIMARY RESISTANCE; INHIBITOR MK-1775; MAMMALIAN TARGET; KINASE INHIBITOR; CANCER-THERAPY; LUNG-CANCER; HUMAN-CELLS; K-RAS AB Direct targeting of rat sarcoma (RAS), which is frequently mutated, has proven to be challenging, and inhibition of individual downstream RAS mediators has resulted in limited clinical efficacy. We designed a chemical screen to identify compounds capable of potentiating mammalian target of rapamycin (mTOR) inhibition in mutant RAS-positive leukemia, and identified a Wee1 inhibitor. Synergy was observed in both mutant neuroblastoma RAS viral oncogene homolog (NRAS)- and mutant kirsten RAS viral oncogene homolog (KRAS)-positive acute myelogenous leukemia (AML) cell lines and primary patient samples. The observed synergy enhanced dephosphorylation of AKT, 4E-binding protein 1 and s6 kinase, and correlated with increased apoptosis. The specificity of Wee1 as the target of MK-1775 was validated by Wee1 knockdown, as well as partial reversal of drug combination-induced apoptosis by a cyclin-dependent kinase 1 (CDK1) inhibitor. Importantly, we also extended our findings to other mutant RAS-expressing malignancies, including mutant NRAS-positive melanoma, and mutant KRAS-positive colorectal cancer, pancreatic cancer and lung cancer. We observed favorable responses with combined Wee1/mTOR inhibition in human cancer cell lines from multiple malignancies, and inhibition of tumor growth in in vivo models of mutant KRAS lung cancer and leukemia. The present study introduces for the first time Wee1 inhibition combined with mTOR inhibition as a novel therapeutic strategy for the selective treatment of mutant RAS-positive leukemia and other mutant RAS-expressing malignancies. C1 [Weisberg, E.; Nonami, A.; Chen, Z.; Sattler, M.; Nelson, E.; Cowens, K.; Christie, A. L.; Mitsiades, C.; Wong, K-K; Griffin, J. D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Liu, F.; Liu, Q.] Chinese Acad Sci, High Magnet Field Lab, Hefei, Peoples R China. [Zhang, J.; Gray, N.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Weisberg, E (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM ellen_weisberg@dfci.harvard.edu; james_griffin@dfci.harvard.edu FU NIH LINCS grant [HG006097]; NIH [CA134660] FX We wish to acknowledge Catherine Sypher, Carmen Da Silva, Elsy Moreno, Lia Palazzolo and Daisy Moreno for their assistance with in vivo studies. NG is supported by NIH LINCS grant HG006097. MS is supported by NIH grant CA134660. NR 49 TC 15 Z9 15 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD JAN PY 2015 VL 29 IS 1 BP 27 EP 37 DI 10.1038/leu.2014.149 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA AY6JX UT WOS:000347673700004 PM 24791855 ER PT J AU Cao, Y Hunter, ZR Liu, X Xu, L Yang, G Chen, J Patterson, CJ Tsakmaklis, N Kanan, S Rodig, S Castillo, JJ Treon, SP AF Cao, Y. Hunter, Z. R. Liu, X. Xu, L. Yang, G. Chen, J. Patterson, C. J. Tsakmaklis, N. Kanan, S. Rodig, S. Castillo, J. J. Treon, S. P. TI The WHIM-like CXCR4(S338X) somatic mutation activates AKT and ERK, and promotes resistance to ibrutinib and other agents used in the treatment of Waldenstrom's Macroglobulinemia SO LEUKEMIA LA English DT Article ID BRUTON TYROSINE KINASE; MYD88 L265P; CXCR4; SURVIVAL; INHIBITION; MYELOMA AB CXCR4(WHIM) somatic mutations are common Waldenstrom's Macroglobulinemia (WM), and are associated with clinical resistance to ibrutinib. We engineered WM cells to express the most common WHIM (Warts, Hypogammaglobulinemia, Infections and Myelokathexis), CXCRS338X mutation in WM. Following SDF-1a stimulation, CXCR4(S338X) WM cells exhibited decreased receptor internalization, enhanced and sustained AKT kinase (AKT) and extracellular regulated kinase (ERK) signaling, decreased poly (ADP-ribose) polymerase and caspase 3 cleavage, and decreased Annexin V staining versus CXCR4 wild-type (WT) cells. CXCR4(S338X)-related signaling and survival effects were blocked by the CXCR4 inhibitor AMD3100. SDF-1a-treated CXCR4(S338X) WM cells showed sustained AKT and ERK activation and decreased apoptotic changes versus CXCR4(WT) cells following ibrutinib treatment, findings which were also reversed by AMD3100. AKT or ERK antagonists restored ibrutinib-triggered apoptotic changes in SDF-1a-treated CXCR4(S338X) WM cells demonstrating their role in SDF-1a-mediated ibrutinib resistance. Enhanced bone marrow pAKT staining was also evident in CXCR4(WHIM) versus CXCR4(WT) WM patients, and remained active despite ibrutinib therapy in CXCR4(WHIM) patients. Last, CXCR4(S338X) WM cells showed varying levels of resistance to other WM relevant therapeutics, including bendamustine, fludarabine, bortezomib and idelalisib in the presence of SDF-1a. These studies demonstrate a functional role for CXCR4(WHIM) mutations, and provide a framework for investigation of CXCR4 inhibitors in WM. C1 [Cao, Y.; Hunter, Z. R.; Liu, X.; Xu, L.; Yang, G.; Chen, J.; Patterson, C. J.; Tsakmaklis, N.; Kanan, S.; Castillo, J. J.; Treon, S. P.] Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. [Cao, Y.; Liu, X.; Yang, G.; Rodig, S.; Castillo, J. J.; Treon, S. P.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Hunter, Z. R.] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. [Rodig, S.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Treon, SP (reprint author), Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, M548,450 Brookline Ave, Boston, MA 02115 USA. EM steven_treon@dfci.harvard.edu OI Castillo, Jorge/0000-0001-9490-7532; Hunter, Zachary/0000-0002-1689-1691 FU Helen Bing Foundation; D'Amato Family Fund for Genomic Discovery; Edward and Linda Nelson Fund FX This work is dedicated in memory of Dr Nicole Muller-Berat Killman, Editor in Chief of Leukemia, whose personal and caring nature, exemplary scientific aptitude and advancement of knowledge to benefit cancer patients through judicious peer review will be missed. The authors also acknowledge the generous support of the Peter and Helen Bing Foundation, the D'Amato Family Fund for Genomic Discovery, the Edward and Linda Nelson Fund for WM Research and the WM patients who provided their samples in support of these studies. Findings of this study were presented at the annual meeting of the American Society for Hematology in 2012 and 2013. NR 25 TC 31 Z9 31 U1 2 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD JAN PY 2015 VL 29 IS 1 BP 169 EP 176 DI 10.1038/leu.2014.187 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA AY6JX UT WOS:000347673700018 PM 24912431 ER PT J AU Bae, J Prabhala, R Voskertchian, A Brown, A Maguire, C Richardson, P Dranoff, G Anderson, KC Munshi, NC AF Bae, J. Prabhala, R. Voskertchian, A. Brown, A. Maguire, C. Richardson, P. Dranoff, G. Anderson, K. C. Munshi, N. C. TI A multiepitope of XBP1, CD138 and CS1 peptides induces myeloma-specific cytotoxic T lymphocytes in T cells of smoldering myeloma patients SO LEUKEMIA LA English DT Article ID POTENTIAL THERAPEUTIC APPLICATION; COLONY-STIMULATING FACTOR; MULTIPLE-MYELOMA; DENDRITIC CELLS; MONOCLONAL GAMMOPATHY; UNDETERMINED SIGNIFICANCE; TRANSCRIPTION FACTOR; ANTITUMOR RESPONSES; COLORECTAL-CANCER; PLASMA-CELLS AB We evaluated a cocktail of HLA-A2-specific peptides including heteroclitic XBP1 US184-192 (YISPWILAV), heteroclitic XBP1 SP367-375 (YLFPQLISV), native CD138(260-268) (GLVGLIFAV) and native CS1(239-247) (SLFVLGLFL), for their ability to elicit multipeptide-specific cytotoxic T lymphocytes (MP-CTLs) using T cells from smoldering multiple myeloma (SMM) patients. Our results demonstrate that MP-CTLs generated from SMM patients' T cells show effective anti-MM responses including CD137 (4-1BB) upregulation, CTL proliferation, interferon-g production and degranulation (CD107a) in an HLA-A2-restricted and peptide-specific manner. Phenotypically, we observed increased total CD3_CD8_ T cells (480%) and cellular activation (CD69_) within the memory SMM MP-CTL (CD45RO_/CD3_CD8_) subset after repeated multipeptide stimulation. Importantly, SMM patients could be categorized into distinct groups by their level of MP-CTL expansion and antitumor activity. In high responders, the effector memory (CCR7 CD45RO_/CD3_CD8_) T-cell subset was enriched, whereas the remaining responders' CTL contained a higher frequency of the terminal effector (CCR7 CD45RO /CD3_CD8_) subset. These results suggest that this multipeptide cocktail has the potential to induce effective and durable memory MP-CTL in SMM patients. Therefore, our findings provide the rationale for clinical evaluation of a therapeutic vaccine to prevent or delay progression of SMM to active disease. C1 [Bae, J.; Prabhala, R.; Brown, A.; Richardson, P.; Dranoff, G.; Anderson, K. C.; Munshi, N. C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bae, J.; Prabhala, R.; Brown, A.; Richardson, P.; Dranoff, G.; Anderson, K. C.; Munshi, N. C.] Harvard Univ, Sch Med, Boston, MA USA. [Prabhala, R.; Munshi, N. C.] VA Boston Healthcare Syst, Boston, MA USA. [Voskertchian, A.] Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. [Maguire, C.] Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Bae, J (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM jooeun_bae@dfci.harvard.edu FU National Institutes of Health [RO1-124929, P50-100007] FX We acknowledge the generous gift of K562-A* 0201 cells from Dr P Cresswell (Yale University, New Haven, CT, USA). We also thank Mr J Daley and Ms S Lazo-Kallanian from the Flow Cytometry facility at Dana-Farber Cancer Institute for providing flow cytometry assistance. This work was supported in part by grants from the National Institutes of Health Grants RO1-124929 to Dr NC Munshi, P50-100007, PO1-78378 and PO1155258 to Drs KC Anderson and NC Munshi, and RO1-50947 to Dr KC Anderson. This research was also supported in part by a kind donation from Mr and Mrs Stewart Nagler. Dr KC Anderson is an American Cancer Society Clinical Research Professor. NR 49 TC 10 Z9 10 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD JAN PY 2015 VL 29 IS 1 BP 218 EP 229 DI 10.1038/leu.2014.159 PG 12 WC Oncology; Hematology SC Oncology; Hematology GA AY6JX UT WOS:000347673700023 PM 24935722 ER PT J AU Schatz, JH Horwitz, SM Teruya-Feldstein, J Lunning, MA Viale, A Huberman, K Socci, ND Lailler, N Heguy, A Dolgalev, I Migliacci, JC Pirun, M Palomba, ML Weinstock, DM Wendel, G AF Schatz, J. H. Horwitz, S. M. Teruya-Feldstein, J. Lunning, M. A. Viale, A. Huberman, K. Socci, N. D. Lailler, N. Heguy, A. Dolgalev, I. Migliacci, J. C. Pirun, M. Palomba, M. L. Weinstock, D. M. Wendel, G. TI Targeted mutational profiling of peripheral T-cell lymphoma not otherwise specified highlights new mechanisms in a heterogeneous pathogenesis SO LEUKEMIA LA English DT Letter ID P53 PROTEIN; EXPRESSION; KINASE; RHOA; SYK; ITK C1 [Schatz, J. H.] Univ Arizona, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA. [Horwitz, S. M.; Lunning, M. A.; Migliacci, J. C.; Palomba, M. L.] Dept Med, New York, NY USA. [Teruya-Feldstein, J.] Dept Pathol, New York, NY USA. [Viale, A.; Huberman, K.; Lailler, N.] Genom Core Lab, New York, NY USA. [Socci, N. D.; Pirun, M.] Bioinformat Core, New York, NY USA. [Heguy, A.; Dolgalev, I.] NYU, Langone Med Ctr, Genome Technol Ctr, New York, NY USA. [Weinstock, D. M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wendel, G.] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10021 USA. EM schatzj@email.arizona.edu; horwitzs@mskcc.org OI Dolgalev, Igor/0000-0003-4451-126X; Schatz, Jonathan/0000-0003-1842-228X FU NCATS NIH HHS [UL1 TR000457]; NCI NIH HHS [R01-CA142798-01, P30 CA008748, R01 CA142798] NR 15 TC 8 Z9 8 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD JAN PY 2015 VL 29 IS 1 BP 237 EP 241 DI 10.1038/leu.2014.261 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA AY6JX UT WOS:000347673700027 PM 25257991 ER PT J AU Pozdnyakova, O Rodig, S Bhandarkar, S Wu, K Thiele, J Hasserjian, R AF Pozdnyakova, O. Rodig, S. Bhandarkar, S. Wu, K. Thiele, J. Hasserjian, R. TI The importance of central pathology review in international trials: a comparison of local versus central bone marrow reticulin grading SO LEUKEMIA LA English DT Letter ID CHRONIC IDIOPATHIC MYELOFIBROSIS; EUROPEAN CONSENSUS; POLYCYTHEMIA-VERA; WORKING GROUP; FIBROSIS; DIAGNOSIS; CRITERIA C1 [Pozdnyakova, O.; Rodig, S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bhandarkar, S.; Wu, K.] Sanofi Oncol, Cambridge, MA USA. [Thiele, J.] Univ Cologne, D-50931 Cologne, Germany. [Hasserjian, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Pozdnyakova, O (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM rhasserjian@partners.org NR 16 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD JAN PY 2015 VL 29 IS 1 BP 241 EP 244 DI 10.1038/leu.2014.262 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA AY6JX UT WOS:000347673700028 PM 25183285 ER PT J AU Visconte, V Lindsley, RC Berlyne, D AF Visconte, Valeria Lindsley, R. Coleman Berlyne, Deborah TI Aplastic Anemia & MDS International Foundation (AA&MDSIF): Bone Marrow Failure Disease Scientific Symposium 2014 SO LEUKEMIA RESEARCH LA English DT Article DE Myelodysplastic syndromes; Aplastic anemia; Paroxysmal nocturnal hemoglobinuria; Genetics; Genomics; Immunobiology; Transplant and non transplant therapies ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; T-CELLS; MUTATIONS AB Bone marrow failure syndromes (BMFS) are characterized by a failure of the hematopoietic stem cells to produce adequate blood cells, resulting in either cytopenia (defect in one or more blood cell lineages) or pancytopenia (defect in all blood cell lineages). BMFS can be inherited or acquired. The pathogenesis of these diseases is very heterogeneous. Research efforts have been made all over the world to improve the basic knowledge of these diseases. The Aplastic Anemia and MDS International Foundation (AA&MDSIF) is an independent nonprofit organization whose mission is to help patients and family members cope with BMFS. Here, we summarize novel scientific discoveries in several BMFS that were presented at the 4th International Bone Marrow Failure Disease Scientific Symposium 2014 that AA&MDSIF sponsored on March 27-28, 2014, in Rockville, MD. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Visconte, Valeria] Cleveland Clin, Taussig Canc Inst, Dept Translat Hematol & Oncol Res, Cleveland, OH 44195 USA. [Lindsley, R. Coleman] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Berlyne, Deborah] Aplast Anemia & MDS Int Fdn, Rockville, MD 20850 USA. RP Visconte, V (reprint author), Cleveland Clin, Taussig Canc Inst, Dept Translat Hematol & Oncol Res, 9500 Euclid Ave R4-053, Cleveland, OH 44195 USA. EM visconv@ccf.org OI Lindsley, Coleman/0000-0001-9822-806X FU Aplastic Anemia 82 MDS International Foundation FX We are thankful to the Aplastic Anemia 82 MDS International Foundation for sponsoring the 4th International Bone Marrow Failure Disease Scientific Symposium 2014. The authors thank all speakers for sharing their clinical and basic research findings in bone marrow failure syndromes. We also thank all the attendees for participating in the meeting. NR 8 TC 3 Z9 4 U1 1 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD JAN PY 2015 VL 39 IS 1 BP 110 EP 113 DI 10.1016/j.leukres.2014.11.008 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA AX3SD UT WOS:000346858200017 PM 25435026 ER PT J AU Pal, SK He, ML Tong, T Wu, HQ Liu, XL Lau, C Wang, JH Warden, C Wu, XW Signoretti, S Choueiri, TK Karam, JA Jones, JO AF Pal, Sumanta K. He, Miaoling Tong, Tommy Wu, Huiqing Liu, Xueli Lau, Clayton Wang, Jin-Hui Warden, Charles Wu, Xiwei Signoretti, Sabina Choueiri, Toni K. Karam, Jose A. Jones, Jeremy O. TI RNA-seq Reveals Aurora Kinase-Driven mTOR Pathway Activation in Patients with Sarcomatoid Metastatic Renal Cell Carcinoma SO MOLECULAR CANCER RESEARCH LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; ENDOTHELIAL-CELLS; TARGETED THERAPY; EXPRESSION; GENE; TEMSIROLIMUS; CANCER; DIFFERENTIATION; IDENTIFICATION; TRANSFORMATION AB Sarcomatoid metastatic renal cell carcinoma (mRCC) is associated with a poor prognosis, and the biology of the disease has been inadequately characterized. RNA sequencing (RNA-seq) was performed on adjacent benign, clear cell, and sarcomatoid components from clinical specimens with sarcomatoid mRCC. M phase and cell-cycle pathways were enriched in sarcomatoid versus adjacent clear cell components, suggesting greater cell proliferation. The expression of aurora kinase A (AURKA) was increased as part of these pathways, and its increased expression was validated by quantitative PCR (qPCR). Immunohistochemical (IHC) analysis revealed that AURKA levels were increased in sarcomatoid tissue compared with their benign or clear cell parts. The increase in AURKA correlated with increased mTOR pathway activity, as evidenced by increased expression of phosphorylated mTOR (S2448) and ribosomal protein S6K (T389). When AURKA was stably expressed in a RCC cell line (Renca), it resulted in increased expression and activity of mTOR, suggesting that overexpression of AURKA can activate the mTOR pathway. These results warrant the analysis of a larger clinical cohort and suggest that targeting AURKA and/or mTOR in patients with sarcomatoid mRCC should be explored. (C) 2014 AACR. C1 [Pal, Sumanta K.] City Hope Comprehens Canc Ctr, Dept Med Oncol & Expt Therapeut, Duarte, CA 91010 USA. [He, Miaoling; Jones, Jeremy O.] City Hope Comprehens Canc Ctr, Dept Mol Pharmacol, Duarte, CA 91010 USA. [Tong, Tommy; Wu, Huiqing] City Hope Comprehens Canc Ctr, Dept Pathol, Duarte, CA 91010 USA. [Liu, Xueli] City Hope Comprehens Canc Ctr, Dept Biostat, Duarte, CA 91010 USA. [Lau, Clayton] City Hope Comprehens Canc Ctr, Dept Surg, Duarte, CA 91010 USA. [Wang, Jin-Hui; Warden, Charles; Wu, Xiwei] City Hope Comprehens Canc Ctr, Duarte, CA 91010 USA. [Signoretti, Sabina] Dana Farber Canc Ctr, Dept Pathol, Boston, MA USA. [Choueiri, Toni K.] Dana Farber Canc Ctr, Dept Med Oncol, Boston, MA USA. [Karam, Jose A.] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA. RP Jones, JO (reprint author), City Hope Comprehens Canc Ctr, Beckman Res Inst, 1500 E Duarte Rd, Duarte, CA 91010 USA. EM jjones@coh.org FU NIH [K12 2K12CA001727-16A1] FX This work was supported by NIH K12 2K12CA001727-16A1 (S. K. Pal). NR 49 TC 17 Z9 17 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD JAN PY 2015 VL 13 IS 1 BP 130 EP 137 DI 10.1158/1541-7786.MCR-14-0352 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AZ0LR UT WOS:000347937400013 PM 25183163 ER PT J AU Calles, A Kwiatkowski, N Cammarata, BK Ercan, D Gray, NS Janne, PA AF Calles, Antonio Kwiatkowski, Nicholas Cammarata, Bernard K. Ercan, Dalia Gray, Nathanael S. Jaenne, Pasi A. TI Tivantinib (ARQ 197) efficacy is independent of MET inhibition in non-small-cell lung cancer cell lines SO MOLECULAR ONCOLOGY LA English DT Article DE Tivantinib; ARQ 197; c-MET; Lung cancer; Crizotinib ID RANDOMIZED PHASE-II; C-MET; TYROSINE KINASE; CYTOTOXIC ACTIVITY; ANTITUMOR-ACTIVITY; PLUS ERLOTINIB; TARGETING MET; COPY NUMBER; EGFR T790M; AMPLIFICATION AB MET targeted therapies are under clinical evaluation for non-small-cell lung cancer (NSCLC) patients. Tyrosine kinase inhibitors (TKI) against MET have varying degrees of specificity. Tivantinib (ARQ 197) is reported to be a non-ATP competitive selective MET inhibitor. We aimed to compare the activity of tivantinib to established MET TKIs in a panel of NSCLC cell lines characterized by their MET dependency and by different relevant genotypes. A549, H3122, PC9 and HCC827, their respective resistant clones PC9 GR4 and HCC827 GR6 and the MET amplified cell lines H1993 and EBC-1 were treated in vitro with tivantinib, crizotinib or PHA-665752. Crizotinib and PHA-665752 showed growth inhibition restricted to MET dependent cell lines. The pattern of activity was related to MET inhibition and downstream signaling inhibition of AKT and ERK1/2, resulting in G(0)/G(1) cycle arrest and apoptosis. In contrast, tivantinib possessed more potent anti-proliferative activity that was not restricted to only MET dependent cell lines. Tivantinib did not inhibit cellular MET activity or phosphorylation of downstream signaling proteins AKT or ERK1/2 in either MET dependent or independent cell lines. Cell cycle analysis demonstrated that tivantinib induced a G(2)/M arrest and induced apoptosis. Tivantinib but not crizotinib effected microtubule dynamics, disrupting mitotic spindles by a mechanism consistent with it functioning as a microtubule depolymerizer. Tivantinib activity is independent of MET signaling in NSCLC and suggests alternative mechanisms of action that should be considered when interpreting the results from on-going clinical studies. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 [Calles, Antonio; Cammarata, Bernard K.; Ercan, Dalia; Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02215 USA. [Calles, Antonio; Cammarata, Bernard K.; Ercan, Dalia; Jaenne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Kwiatkowski, Nicholas; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Kwiatkowski, Nicholas; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Jaenne, Pasi A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Jaenne, Pasi A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, HIM223,450 Brookline Ave, Boston, MA 02115 USA. EM pasi_janne@dfci.harvard.edu OI Calles, Antonio/0000-0002-2547-1947 FU National Cancer Institute at the National Institutes of Health [R01CA135257]; Spanish Medical Oncology Society FX This work was supported in part by the National Cancer Institute at the National Institutes of Health by R01CA135257 (P.A. Janne). A. Calles is a grant recipient from the Spanish Medical Oncology Society. NR 39 TC 11 Z9 11 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1574-7891 EI 1878-0261 J9 MOL ONCOL JI Mol. Oncol. PD JAN PY 2015 VL 9 IS 1 BP 260 EP 269 DI 10.1016/j.molonc.2014.08.011 PG 10 WC Oncology SC Oncology GA AY9IL UT WOS:000347863700021 PM 25226813 ER PT J AU Kuffner, R Zach, N Norel, R Hawe, J Schoenfeld, D Wang, LX Li, G Fang, L Mackey, L Hardiman, O Cudkowicz, M Sherman, A Ertaylan, G Grosse-Wentrup, M Hothorn, T van Ligtenberg, J Macke, JH Meyer, T Scholkopf, B Tran, L Vaughan, R Stolovitzky, G Leitner, ML AF Kueffner, Robert Zach, Neta Norel, Raquel Hawe, Johann Schoenfeld, David Wang, Liuxia Li, Guang Fang, Lilly Mackey, Lester Hardiman, Orla Cudkowicz, Merit Sherman, Alexander Ertaylan, Gokhan Grosse-Wentrup, Moritz Hothorn, Torsten van Ligtenberg, Jules Macke, Jakob H. Meyer, Timm Schoelkopf, Bernhard Tran, Linh Vaughan, Rubio Stolovitzky, Gustavo Leitner, Melanie L. TI Crowdsourced analysis of clinical trial data to predict amyotrophic lateral sclerosis progression SO NATURE BIOTECHNOLOGY LA English DT Article ID URIC-ACID LEVELS; BODY-MASS INDEX; FUNCTIONAL RATING-SCALE; ALSFRS-R SCORE; DISEASE PROGRESSION; PROGNOSTIC-FACTORS; PARKINSON-DISEASE; BLOOD-PRESSURE; SURVIVAL; POPULATION AB Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with substantial heterogeneity in its clinical presentation. This makes diagnosis and effective treatment difficult, so better tools for estimating disease progression are needed. Here, we report results from the DREAM-Phil Bowen ALS Prediction Prize4Life challenge. In this crowdsourcing competition, competitors developed algorithms for the prediction of disease progression of 1,822 ALS patients from standardized, anonymized phase 2/3 clinical trials. The two best algorithms outperformed a method designed by the challenge organizers as well as predictions by ALS clinicians. We estimate that using both winning algorithms in future trial designs could reduce the required number of patients by at least 20%. The DREAM-Phil Bowen ALS Prediction Prize4Life challenge also identified several potential nonstandard predictors of disease progression including uric acid, creatinine and surprisingly, blood pressure, shedding light on ALS pathobiology. This analysis reveals the potential of a crowdsourcing competition that uses clinical trial data for accelerating ALS research and development. C1 [Kueffner, Robert] German Res Ctr Environm Hlth, Inst Bioinformat & Syst Biol, Munich, Germany. [Kueffner, Robert; Hawe, Johann] Univ Munich, Dept Informat, Munich, Germany. [Zach, Neta; Leitner, Melanie L.] Prize4Life, Tel Aviv, Israel. [Zach, Neta; Leitner, Melanie L.] Prize4Life, Cambridge, MA USA. [Norel, Raquel] IBM TJ Watson Res Ctr, Yorktown Hts, NY USA. [Schoenfeld, David] Massachusetts Gen Hosp, MGH Biostat Ctr, Boston, MA 02114 USA. [Schoenfeld, David] Harvard Univ, Sch Med, Charlestown, MA USA. [Wang, Liuxia; Li, Guang] Sentrana Inc, Washington, DC USA. [Fang, Lilly] Latham&Watkins LLP, Silicon Valley, CA USA. [Mackey, Lester] Stanford Univ, Dept Stat, Stanford, CA 94305 USA. [Hardiman, Orla] Beaumont Hosp, Dept Neurosci, Dublin 9, Ireland. [Hardiman, Orla] Trinity Coll Dublin, Dublin, Ireland. [Cudkowicz, Merit; Sherman, Alexander] Massachusetts Gen Hosp, Neurol Clin Res Inst, Charlestown, MA USA. [Ertaylan, Gokhan] Univ Luxembourg, Esch Alzette, Luxembourg Ctr Syst Biomed, Luxembourg, Luxembourg. [Grosse-Wentrup, Moritz; Meyer, Timm; Schoelkopf, Bernhard] Max Planck Inst Intelligent Syst, Tubingen, Germany. [Hothorn, Torsten] Univ Zurich, Inst Social & Prevent Med, Zurich, Switzerland. [van Ligtenberg, Jules; Vaughan, Rubio] Orca XL Problem Solvers, Amsterdam, Netherlands. [Macke, Jakob H.] Max Planck Inst Biol Cybernet, Tubingen, Germany. [Macke, Jakob H.] Bernstein Ctr Computat Neurosci, Tubingen, Germany. [Tran, Linh] Univ Calif Berkeley, Berkeley Sch Publ Hlth, Berkeley, CA USA. [Leitner, Melanie L.] Biogen Idec Inc, ALS Innovat Hub, Cambridge, MA USA. RP Kuffner, R (reprint author), German Res Ctr Environm Hlth, Inst Bioinformat & Syst Biol, Munich, Germany. EM robert.kueffner@helmholtz-muenchen.de; nzach@prize4life.org OI Norel, Raquel/0000-0001-7737-4172; Ertaylan, Gokhan/0000-0001-5602-6435; Hardiman, Orla/0000-0003-2610-1291 NR 49 TC 33 Z9 34 U1 2 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JAN PY 2015 VL 33 IS 1 BP 51 EP U292 DI 10.1038/nbt.3051 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA AY7AR UT WOS:000347714200027 PM 25362243 ER PT J AU Schlaeger, TM Daheron, L Brickler, TR Entwisle, S Chan, K Cianci, A DeVine, A Ettenger, A Fitzgerald, K Godfrey, M Gupta, D McPherson, J Malwadkar, P Gupta, M Bell, B Doi, A Jung, N Li, X Lynes, MS Brookes, E Cherry, ABC Demirbas, D Tsankov, AM Zon, LI Rubin, LL Feinberg, AP Meissner, A Cowan, CA Daley, GQ AF Schlaeger, Thorsten M. Daheron, Laurence Brickler, Thomas R. Entwisle, Samuel Chan, Karrie Cianci, Amelia DeVine, Alexander Ettenger, Andrew Fitzgerald, Kelly Godfrey, Michelle Gupta, Dipti McPherson, Jade Malwadkar, Prerana Gupta, Manav Bell, Blair Doi, Akiko Jung, Namyoung Li, Xin Lynes, Maureen S. Brookes, Emily Cherry, Anne B. C. Demirbas, Didem Tsankov, Alexander M. Zon, Leonard I. Rubin, Lee L. Feinberg, Andrew P. Meissner, Alexander Cowan, Chad A. Daley, George Q. TI A comparison of non-integrating reprogramming methods SO NATURE BIOTECHNOLOGY LA English DT Article ID PLURIPOTENT STEM-CELLS; HUMAN SOMATIC-CELLS; HUMAN IPS CELLS; HUMAN FIBROBLASTS; DEFINED FACTORS; MESSENGER-RNA; GENERATION; LINES; DIFFERENTIATION; DERIVATION AB Human induced pluripotent stem cells (hiPSCs(1-3)) are useful in disease modeling and drug discovery, and they promise to provide a new generation of cell-based therapeutics. To date there has been no systematic evaluation of the most widely used techniques for generating integration-free hiPSCs. Here we compare Sendai-viral (SeV)(4), episomal (Epi)(5) and mRNA transfection mRNA(6) methods using a number of criteria. All methods generated high-quality hiPSCs, but significant differences existed in aneuploidy rates, reprogramming efficiency, reliability and workload. We discuss the advantages and shortcomings of each approach, and present and review the results of a survey of a large number of human reprogramming laboratories on their independent experiences and preferences. Our analysis provides a valuable resource to inform the use of specific reprogramming methods for different laboratories and different applications, including clinical translation. C1 [Schlaeger, Thorsten M.; Chan, Karrie; Cianci, Amelia; DeVine, Alexander; Ettenger, Andrew; Fitzgerald, Kelly; Godfrey, Michelle; Gupta, Dipti; McPherson, Jade; Malwadkar, Prerana; Gupta, Manav; Bell, Blair; Brookes, Emily; Cherry, Anne B. C.; Zon, Leonard I.; Daley, George Q.] Boston Childrens Hosp, Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA USA. [Schlaeger, Thorsten M.; Daheron, Laurence; Brickler, Thomas R.; Entwisle, Samuel; Lynes, Maureen S.; Tsankov, Alexander M.; Zon, Leonard I.; Rubin, Lee L.; Meissner, Alexander; Cowan, Chad A.; Daley, George Q.] Harvard Stem Cell Inst, Cambridge, MA USA. [Doi, Akiko; Jung, Namyoung; Li, Xin; Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD USA. [Doi, Akiko; Jung, Namyoung; Li, Xin; Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD USA. [Doi, Akiko] MIT, Dept Biol, Cambridge, MA 02139 USA. [Cherry, Anne B. C.; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA USA. [Demirbas, Didem] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Div Genet & Genom, Boston, MA USA. [Tsankov, Alexander M.; Meissner, Alexander; Cowan, Chad A.] Broad Inst, Cambridge, MA USA. [Rubin, Lee L.; Cowan, Chad A.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA USA. [Cowan, Chad A.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Daley, George Q.] Childrens Hosp Boston, Howard Hughes Med Inst, Boston, MA USA. [Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Schlaeger, TM (reprint author), Boston Childrens Hosp, Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA USA. EM thorsten.schlaeger@childrens.harvard.edu; george.daley@childrens.harvard.edu OI Brookes, Emily/0000-0003-2175-4349; Ettenger, Andrew/0000-0003-2258-4329; Cianci, Antonio/0000-0003-2758-3413; Tzankov, Alexandar/0000-0002-1100-3819 FU National Heart, Lung, and Blood Institute (NHLBI) Progenitor Cell Biology Consortium [R01HL75737, U01HL107440, UO1-HL100001, U01HL87402, U01HL100408]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R24DK092760]; National Institute of Neurological Disorders and Stroke (NINDS) [PO1NS066888]; SMA Foundation; Jerome Le Jeune Foundation; EMBO postdoctoral fellowship; Harvard Stem Cell Institute FX We would like to thank B. Hamilton (Stemgent) for miRNA reprogramming agents and protocols, G. Mostoslavsky (Boston University) for human STEMCCA lentiviral plasmid constructs, M. Armant (Boston Children's Hospital) for MRC5 and hCD34+ cells, G. MacLean (Boston Children's Hospital) for advice on episomal blood reprogramming and S. D'Souza (Icahn School of Medicine at Mount Sinai) for a list of contacts for human cell reprogramming laboratories. This work was supported in part by grants R01HL75737, U01HL107440, UO1-HL100001, U01HL87402 and U01HL100408 (National Heart, Lung, and Blood Institute (NHLBI) Progenitor Cell Biology Consortium), R24DK092760 (the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)), PO1NS066888 (the National Institute of Neurological Disorders and Stroke (NINDS)), by the SMA Foundation, the Jerome Le Jeune Foundation, an EMBO postdoctoral fellowship (E. B.) and the Harvard Stem Cell Institute. NR 36 TC 63 Z9 68 U1 16 U2 63 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JAN PY 2015 VL 33 IS 1 BP 58 EP U230 DI 10.1038/nbt.3070 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA AY7AR UT WOS:000347714200028 PM 25437882 ER PT J AU Kim, J Li, WA Choi, Y Lewin, SA Verbeke, CS Dranoff, G Mooney, DJ AF Kim, Jaeyun Li, Weiwei Aileen Choi, Youngjin Lewin, Sarah A. Verbeke, Catia S. Dranoff, Glenn Mooney, David J. TI Injectable, spontaneously assembling, inorganic scaffolds modulate immune cells in vivo and increase vaccine efficacy SO NATURE BIOTECHNOLOGY LA English DT Article ID MESOPOROUS SILICA NANOPARTICLES; DENDRITIC CELLS; NALP3 INFLAMMASOME; DRUG-DELIVERY; T-FH; ANTIGEN; RESPONSES; INNATE; BIOMATERIALS; DEGRADATION AB Implanting materials in the body to program host immune cells is a promising alternative to transplantation of cells manipulated ex vivo to direct an immune response, but doing so requires a surgical procedure. Here we demonstrate that high-aspect-ratio, mesoporous silica rods (MSRs) injected with a needle spontaneously assemble in vivo to form macroporous structures that provide a 3D cellular microenvironment for host immune cells. In mice, substantial numbers of dendritic cells are recruited to the pores between the scaffold rods. The recruitment of dendritic cells and their subsequent homing to lymph nodes can be modulated by sustained release of inflammatory signals and adjuvants from the scaffold. Moreover, injection of an MSR-based vaccine formulation enhances systemic helper T cells T(H)1 and T(H)2 serum antibody and cytotoxic T-cell levels compared to bolus controls. These findings suggest that injectable MSRs may serve as a multifunctional vaccine platform to modulate host immune cell function and provoke adaptive immune responses. C1 [Kim, Jaeyun; Li, Weiwei Aileen; Verbeke, Catia S.; Mooney, David J.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Kim, Jaeyun; Li, Weiwei Aileen; Lewin, Sarah A.; Verbeke, Catia S.; Mooney, David J.] Harvard Univ, Wyss Inst Biologically Inspired Engn, Boston, MA 02115 USA. [Kim, Jaeyun; Choi, Youngjin] Sungkyunkwan Univ, Sch Chem Engn, Suwon, South Korea. [Dranoff, Glenn] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dranoff, Glenn] Harvard Univ, Sch Med, Boston, MA USA. RP Mooney, DJ (reprint author), Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. EM mooneyd@seas.harvard.edu FU National Institutes of Health (NIH) [1R01EB015498]; National Science Foundation (NSF) Graduate Research Fellowship Program (GRFP); Wyss Institute for Biologically Inspired Engineering at Harvard University; National Research Foundation (NRF) - National Research Foundation under the Ministry of Science, ICT & Future Planning, Korea [2012R1A1A1042735, 2010-0027955]; NIH [UL1 TR001102] FX This work was supported by the National Institutes of Health (NIH) (1R01EB015498), the National Science Foundation (NSF) Graduate Research Fellowship Program (GRFP), the Wyss Institute for Biologically Inspired Engineering at Harvard University, and National Research Foundation (NRF) grants (2012R1A1A1042735, 2010-0027955) funded by the National Research Foundation under the Ministry of Science, ICT & Future Planning, Korea. We also thank Dana-Farber/Harvard Cancer Center (DF/HCC) Research Pathology Core and R. Bronson for the examination of the histology slides and J. Weaver from the Wyss Institute of Biologically Inspired Engineering for his help with scanning electron microscopy (SEM). Lastly, we thank R. Betensky from the Department of Biostatistics, Harvard School of Public Health and the Harvard Catalyst for her help with statistical analysis; Harvard Catalyst is supported, in part, by the NIH (UL1 TR001102). NR 50 TC 53 Z9 53 U1 23 U2 104 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JAN PY 2015 VL 33 IS 1 BP 64 EP U241 DI 10.1038/nbt.3071 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA AY7AR UT WOS:000347714200029 PM 25485616 ER PT J AU Zuris, JA Thompson, DB Shu, Y Guilinger, JP Bessen, JL Hu, JH Maeder, ML Joung, JK Chen, ZY Liu, DR AF Zuris, John A. Thompson, David B. Shu, Yilai Guilinger, John P. Bessen, Jeffrey L. Hu, Johnny H. Maeder, Morgan L. Joung, J. Keith Chen, Zheng-Yi Liu, David R. TI Cationic lipid-mediated delivery of proteins enables efficient protein-based genome editing in vitro and in vivo SO NATURE BIOTECHNOLOGY LA English DT Article ID SUPERCHARGED PROTEINS; MAMMALIAN-CELLS; INTRACELLULAR DELIVERY; NUCLEASE SPECIFICITY; ENDOSOMAL ESCAPE; GENE-EXPRESSION; RNA; CAS9; CRISPR; SIRNA AB Efficient intracellular delivery of proteins is needed to fully realize the potential of protein therapeutics. Current methods of protein delivery commonly suffer from low tolerance for serum, poor endosomal escape and limited in vivo efficacy. Here we report that common cationic lipid nucleic acid transfection reagents can potently deliver proteins that are fused to negatively supercharged proteins, that contain natural anionic domains or that natively bind to anionic nucleic acids. This approach mediates the potent delivery of nM concentrations of Cre recombinase, TALE- and Cas9-based transcription activators, and Cas9:sgRNA nuclease complexes into cultured human cells in media containing 10% serum. Delivery of unmodified Cas9:sgRNA complexes resulted in up to 80% genome modification with substantially higher specificity compared to DNA transfection. This approach also mediated efficient delivery of Cre recombinase and Cas9:sgRNA complexes into the mouse inner ear in vivo, achieving 90% Cre-mediated recombination and 20% Cas9-mediated genome modification in hair cells. C1 [Zuris, John A.; Thompson, David B.; Guilinger, John P.; Bessen, Jeffrey L.; Hu, Johnny H.; Liu, David R.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Zuris, John A.; Thompson, David B.; Guilinger, John P.; Bessen, Jeffrey L.; Hu, Johnny H.; Liu, David R.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Shu, Yilai; Chen, Zheng-Yi] Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. [Shu, Yilai; Chen, Zheng-Yi] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Shu, Yilai] Fudan Univ, Eye Ear Nose & Throat Hosp, Shanghai Med Coll, Dept Otol & Skull Base Surg, Shanghai 200433, Peoples R China. [Shu, Yilai] Minist Hearing Med, Key Lab Hlth, Shanghai, Peoples R China. [Maeder, Morgan L.; Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Maeder, Morgan L.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Maeder, Morgan L.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA USA. [Maeder, Morgan L.; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, 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 Ruth L. Kirchstein National Research Service Award [F32 GM 106601-2]; US National Institutes of Health (NIH) [R01 GM095501, R01 DC006908]; Defense Advanced Research Projects Agency [HR0011-11-2-0003, N66001-12-C-4207]; Howard Hughes Medical Institute (HHMI); Bertarelli Foundation; David-Shulsky Foundation; Frederick and Ines Yeatts Hair Cell Regeneration grant; National Nature Science Foundation of China [NSFC81300824]; National Science Foundation Graduate Research Fellowship Program [DGE1144152]; NIH Director's Pioneer Award [DP1 GM105378] FX J.A.Z. is a Ruth L. Kirchstein National Research Service Awards Postdoctoral Fellow (F32 GM 106601-2) D.B.T., J.P.G. and J.L.B. were supported by US National Institutes of Health (NIH) R01 GM095501 (to D. R. L.), Defense Advanced Research Projects Agency HR0011-11-2-0003 (to D. R. L.) and N66001-12-C-4207 (to D. R. L.), and the Howard Hughes Medical Institute (HHMI). D.R.L. was supported as a HHMI Investigator. Z.-Y.C. was supported by US National Institutes of Health (R01 DC006908), the Bertarelli Foundation, and the David-Shulsky Foundation. Y.S. was supported by the Frederick and Ines Yeatts Hair Cell Regeneration grant and by The National Nature Science Foundation of China NSFC81300824. J.H.H. was supported by National Science Foundation Graduate Research Fellowship Program (DGE1144152). M.L.M. and J.K.J. were supported by an NIH Director's Pioneer Award (DP1 GM105378). We thank A. Lawson, M. Sonnett, R. Xiao, S. Wang and J. Gehrke for technical assistance. We thank A. Edge, Massachusetts Eye & Ear Infirmary, Boston, for mouse embryonic stem cell (ES) line Tau-GFP and J. Johnson, Southwestern Medical Center, University of Texas, for floxPtdTomato mice (The Jackson Laboratory). NR 46 TC 163 Z9 168 U1 30 U2 202 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JAN PY 2015 VL 33 IS 1 BP 73 EP 80 DI 10.1038/nbt.3081 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA AY7AR UT WOS:000347714200030 PM 25357182 ER PT J AU Lam, SS Martell, JD Kamer, KJ Deerinck, TJ Ellisman, MH Mootha, VK Ting, AY AF Lam, Stephanie S. Martell, Jeffrey D. Kamer, Kimberli J. Deerinck, Thomas J. Ellisman, Mark H. Mootha, Vamsi K. Ting, Alice Y. TI Directed evolution of APEX2 for electron microscopy and proximity labeling SO NATURE METHODS LA English DT Article ID MITOCHONDRIAL CALCIUM UNIPORTER; ASCORBATE PEROXIDASE; HORSERADISH-PEROXIDASE; HYDROGEN-PEROXIDE; CELL-SURVIVAL; CA2+ UPTAKE; MICU1; MEMBRANE; PROTEIN; INACTIVATION AB APEX is an engineered peroxidase that functions as an electron microscopy tag and a promiscuous labeling enzyme for live-cell proteomics. Because limited sensitivity precludes applications requiring low APEX expression, we used yeast-display evolution to improve its catalytic efficiency. APEX2 is far more active in cells, enabling the use of electron microscopy to resolve the submitochondrial localization of calcium uptake regulatory protein MICU1. APEX2 also permits superior enrichment of endogenous mitochondrial and endoplasmic reticulum membrane proteins. C1 [Lam, Stephanie S.; Martell, Jeffrey D.; Ting, Alice Y.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Kamer, Kimberli J.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Deerinck, Thomas J.; Ellisman, Mark H.] Univ Calif San Diego, Natl Ctr Microscopy & Imaging Res, La Jolla, CA 92093 USA. [Ellisman, Mark H.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP Ting, AY (reprint author), MIT, Dept Chem, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM ating@mit.edu FU US National Institutes of Health [Dp1 0D003961, P41 GM103412, R01GM086197, 5R01GM077465-08]; Howard Hughes Medical Institute; Howard Hughes Medical Institute Collaborative Initiative Award; US National Science Foundation; National Defense Science and Engineering Graduate Fellowships FX We acknowledge funding from the US National Institutes of Health (Dp1 0D003961 to A.Y.T.; P41 GM103412, R01GM086197 to M.H.E.; 5R01GM077465-08 to V.K.M.), the Howard Hughes Medical Institute (V.K.M.), and the Howard Hughes Medical Institute Collaborative Initiative Award (A.Y.T.). S.S.L. and J.D.M. were supported by US National Science Foundation Graduate Research Fellowships and National Defense Science and Engineering Graduate Fellowships. N. Watson acquired EM images of MICU1-APEX2. V. Hung provided APEX2-Stx17 and ATP5J-APEX2 EM images. K. Cox (Massachusetts Institute of Technology) provided some plasmids. FACS experiments were performed at the Koch Institute Swanson Biotechnology Center Flow Cytometry Facility. Color bright-field imaging was performed at the Koch Institute Microcopy Core Facility. We thank C. Drennan for use of her Cary300 spectrophotometer. D. McSwiggen assisted with enzyme purification. We thank T. Poulos, K. White, and the laboratory of D. Wittrup for advice. NR 26 TC 78 Z9 79 U1 12 U2 53 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 EI 1548-7105 J9 NAT METHODS JI Nat. Methods PD JAN PY 2015 VL 12 IS 1 BP 51 EP 54 PG 4 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA AY6HW UT WOS:000347668600017 PM 25419960 ER PT J AU Pivtoraiko, VN Abrahamson, EE Leurgans, SE DeKosky, ST Mufson, EJ Ikonomovic, MD AF Pivtoraiko, Violetta N. Abrahamson, Eric E. Leurgans, Sue E. DeKosky, Steven T. Mufson, Elliott J. Ikonomovic, Milos D. TI Cortical pyroglutamate amyloid-beta levels and cognitive decline in Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Article DE Pyroglutamate-modified A beta; Amyloid-beta; Alzheimer's disease; Posterior cingulate cortex; MCI; Episodic memory ID EPISODIC MEMORY RETRIEVAL; PROTEIN A-BETA; OLDER PERSONS; NEUROPATHOLOGIC ASSESSMENT; SENILE PLAQUES; ASSOCIATION GUIDELINES; SYNAPTIC PLASTICITY; NATIONAL INSTITUTE; GLUTAMINYL CYCLASE; PRECURSOR PROTEIN AB Posterior cingulate cortex (PCC) accumulates amyloid-beta (A beta) early in Alzheimer's disease (AD). The relative concentrations of full-length Ab and truncated, pyroglutamate-modified A beta (NpE3) forms, and their correlations to cognitive dysfunction in AD, are unknown. We quantified A beta NpE3-42, A beta NpE3-40, A beta 1-42, and A beta 1-40 concentrations in soluble (nonfibrillar) and insoluble (fibrillar) pools in PCC from subjects with an antemortem clinical diagnosis of no cognitive impairment, mild cognitive impairment, or mild-moderate AD. In clinical AD, increased PCC concentrations of Ab were observed for all A beta forms in the insoluble pool but only for A beta 1-42 in the soluble pool. Lower Mini-Mental State Exam and episodic memory scores correlated most strongly with higher concentrations of soluble and insoluble A beta 1-42. Greater neuropathology severity by Consortium to Establish a Registry for Alzheimer's Disease and National Institute on Aging-Reagan pathologic criteria was associated with higher concentrations of all measured Ab forms, except soluble A beta NpE3-40. Low concentrations of soluble pyroglutamate A beta across clinical groups likely reflect its rapid sequestration into plaques, thus, the conversion to fibrillar A beta may be a therapeutic target. Published by Elsevier Inc. C1 [Pivtoraiko, Violetta N.; Abrahamson, Eric E.; Ikonomovic, Milos D.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. [Abrahamson, Eric E.; Ikonomovic, Milos D.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Leurgans, Sue E.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [DeKosky, Steven T.] Univ Virginia, Sch Med, Dept Neurol, Charlottesville, VA 22908 USA. [Mufson, Elliott J.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Ikonomovic, Milos D.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. RP Ikonomovic, MD (reprint author), Univ Pittsburgh, Dept Neurol, 200 Lothrop St,BSTWR S 521, Pittsburgh, PA 15213 USA. EM ikonomovicmd@upmc.edu FU National Institute on Aging, National Institutes of Health [PO1AG014449, PO1AG025204, RO1AG043375, P30AG10161] FX This study was supported by grants PO1AG014449, PO1AG025204, RO1AG043375 and P30AG10161 from the National Institute on Aging, National Institutes of Health. The authors are indebted to the Catholic nuns, priests, and lay brothers who participated in the Rush Religious Orders Study. They are grateful to Dr Ana W. Capuano (Rush University Medical Center) for assistance with statistical analyses and to Mr. William Paljug for expert technical assistance. NR 58 TC 6 Z9 6 U1 2 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JAN PY 2015 VL 36 IS 1 BP 12 EP 19 DI 10.1016/j.neurobiolaging.2014.06.021 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA AY2HD UT WOS:000347408600003 PM 25048160 ER PT J AU Ward, AM Mormino, EC Huijbers, W Schultz, AP Hedden, T Sperling, RA AF Ward, Andrew M. Mormino, Elizabeth C. Huijbers, Willem Schultz, Aaron P. Hedden, Trey Sperling, Reisa A. TI Relationships between default-mode network connectivity, medial temporal lobe structure, and age-related memory deficits SO NEUROBIOLOGY OF AGING LA English DT Article DE Magnetic resonance imaging; Memory; Structural equation modeling; Aging; Cognitive aging ID INTRINSIC FUNCTIONAL CONNECTIVITY; NORMAL OLDER-ADULTS; MILD COGNITIVE IMPAIRMENT; EARLY ALZHEIMERS-DISEASE; WHITE-MATTER; AMYLOID DEPOSITION; RESTING-STATE; EPISODIC MEMORY; HUMAN BRAIN; CARDIORESPIRATORY FITNESS AB Advanced aging negatively impacts memory performance. Brain aging has been associated with shrinkage in medial temporal lobe structures essential for memoryd-including hippocampus and entorhinal cortex-and with deficits in default-mode network connectivity. Yet, whether and how these imaging markers are relevant to age-related memory deficits remains a topic of debate. Using a sample of 182 older (age 74.6 +/- 6.2 years) and 66 young (age 22.2 +/- 3.6 years) participants, this study examined relationships among memory performance, hippocampus volume, entorhinal cortex thickness, and default-mode network connectivity across aging. All imaging markers and memory were significantly different between young and older groups. Each imaging marker significantly mediated the relationship between age and memory performance and collectively accounted for most of the variance in age-related memory performance. Within older participants, default-mode connectivity and hippocampus volume were independently associated with memory. Structural equation modeling of cross-sectional data within older participants suggest that entorhinal thinning may occur before reduced default-mode connectivity and hippocampal volume loss, which in turn lead to deficits in memory performance. (C) 2015 Elsevier Inc. All rights reserved. C1 [Ward, Andrew M.; Huijbers, Willem; Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Ward, Andrew M.; Mormino, Elizabeth C.; Huijbers, Willem; Schultz, Aaron P.; Sperling, Reisa A.] Boston Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02118 USA. [Ward, Andrew M.; Huijbers, Willem; Schultz, Aaron P.; Hedden, Trey; Sperling, Reisa A.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Hedden, Trey] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Sperling, Reisa A.] Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. RP Sperling, RA (reprint author), Brigham & Womens Hosp, Dept Neurol, 221 Longwood Ave, Boston, MA 02115 USA. EM rsperling@rics.bwh.harvard.edu OI Ward, Andrew/0000-0001-6948-4814 FU National Institute on Aging [R01 AG027435, P01AG036694, P50AG005134, K24 AG035007, K01AG040197, F32 AG044054]; European Molecular Biology Organization [ALTF 318-2011]; National Institute of Biomedical Imaging and Bioengineering [P41EB015896, P41] FX This work was supported by National Institute on Aging R01 AG027435, P01AG036694, P50AG005134, K24 AG035007 (Reisa A. Sperling), K01AG040197 (Trey Hedden), F32 AG044054 (Elizabeth C. Mormino), and the European Molecular Biology Organization ALTF 318-2011 (Willem Huijbers). The authors gratefully acknowledge the collaborators and contributors to the Harvard Aging Brain Study (http://www.martinos. org/harvardagingbrain/Acknowledgements.html), the Martinos Center staff, including Mary Foley and Larry White, and the contributions of all of our research participants. This research was carried out in whole or in part at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41EB015896, a P41 Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bioengineering. NR 114 TC 12 Z9 13 U1 4 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JAN PY 2015 VL 36 IS 1 BP 265 EP 272 DI 10.1016/j.neurobiolaging.2014.06.028 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA AY2HD UT WOS:000347408600028 PM 25113793 ER PT J AU Chang, LH Yotsumoto, Y Salat, DH Andersen, GJ Watanabe, T Sasaki, Y AF Chang, Li-Hung Yotsumoto, Yuko Salat, David H. Andersen, George J. Watanabe, Takeo Sasaki, Yuka TI Reduction in the retinotopic early visual cortex with normal aging and magnitude of perceptual learning SO NEUROBIOLOGY OF AGING LA English DT Article DE Cortical surface size; Aging; Early visual area; Perceptual learning; Retinotopic mapping ID HUMAN CEREBRAL-CORTEX; SURFACE-BASED ANALYSIS; WHITE-MATTER; OLDER-ADULTS; GRAY-MATTER; IN-VIVO; DIFFERENTIAL VULNERABILITY; TEXTURE-DISCRIMINATION; PREFRONTAL GRAY; FUNCTIONAL MRI AB Although normal aging is known to reduce cortical structures globally, the effects of aging on local structures and functions of early visual cortex are less understood. Here, using standard retinotopic mapping and magnetic resonance imaging morphologic analyses, we investigated whether aging affects areal size of the early visual cortex, which were retinotopically localized, and whether those morphologic measures were associated with individual performance on visual perceptual learning. First, significant age-associated reduction was found in the areal size of V1, V2, and V3. Second, individual ability of visual perceptual learning was significantly correlated with areal size of V3 in older adults. These results demonstrate that aging changes local structures of the early visual cortex, and the degree of change may be associated with individual visual plasticity. (C) 2015 Elsevier Inc. All rights reserved. C1 [Chang, Li-Hung; Watanabe, Takeo; Sasaki, Yuka] Brown Univ, Dept Cognit Linguist & Psychol Sci, Providence, RI 02912 USA. [Chang, Li-Hung] Natl Yang Ming Univ, Sch Humanities & Social Sci, Educ Ctr Humanities & Social Sci, Taipei 112, Taiwan. [Yotsumoto, Yuko; Salat, David H.; Sasaki, Yuka] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Yotsumoto, Yuko] Keio Univ, Global Ctr Excellence Program, Ctr Adv Res Log & Sensibil, Minato Ku, Tokyo, Japan. [Salat, David H.; Sasaki, Yuka] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Andersen, George J.] Univ Calif Riverside, Dept Psychol, Riverside, CA 92521 USA. RP Sasaki, Y (reprint author), Brown Univ, Dept Cognit Linguist & Psychol Sci, 190 Thayer St, Providence, RI 02912 USA. EM yuka_sasaki@brown.edu FU National Institutes of Health [R01EY015980, R01EY019466, R01AG031941, R01MH091801]; National Center for Research Resources [P41RR14075, S10RR021110]; Japan Society for the Promotion of Science [23680028, 24330208]; Strategic Information and Communications R&D Promotion (SCOPE) [120800000480]; Harvard Cooperative Program on Aging; Massachusetts General Hospital; Athinoula A. Martinos Center for Biomedical Imaging FX Supported by funding from of National Institutes of Health (R01EY015980, R01EY019466, R01AG031941, and R01MH091801), National Center for Research Resources (P41RR14075 and S10RR021110), Japan Society for the Promotion of Science (23680028, 24330208), Strategic Information and Communications R&D Promotion (SCOPE), grant number: 120800000480, Harvard Cooperative Program on Aging, Massachusetts General Hospital, and the Athinoula A. Martinos Center for Biomedical Imaging. The authors also acknowledge the assistance and the facility support from Brookline Senior Center. NR 74 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JAN PY 2015 VL 36 IS 1 BP 315 EP 322 DI 10.1016/j.neurobiolaging.2014.08.025 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA AY2HD UT WOS:000347408600034 PM 25277041 ER PT J AU Swanson, GP Jones, WE Ha, CS Jenkins, CA Kumar, AP Basler, J AF Swanson, Gregory P. Jones, William E., III Ha, Chul S. Jenkins, Carol A. Kumar, Addanki Pratap Basler, Joseph TI Tolerance of Phellodendron amurense Bark Extract (Nexrutine (R)) in Patients with Human Prostate Cancer SO PHYTOTHERAPY RESEARCH LA English DT Article DE Nexrutine (R); Phellodendron amurense extract; prostate cancer; prostatectomy; radiation therapy; combined modality ID ANDROGEN-DEPRIVATION THERAPY; DEFINITIVE RADIOTHERAPY; ADJUVANT; INHIBITION; CARCINOMA; RISK; MEN AB Phellodendron amurense bark extract (Nexrutine (R)) has shown a favorable effect on prostate cancer in vivo and in vitro. We evaluated its tolerance in patients undergoing surgery or radiation for prostate cancer. Patients received Nexrutine (R) orally (500mg tid) either 1 to 2 months preoperatively or 1 to 2months prior to and with radiation therapy. Common Terminology Criteria for Adverse Events were used to measure tolerance. In total, 21 patients (9 surgery and 12 radiation) underwent treatment. During the Nexrutine (R) alone component, there were two transient grade 3 toxicities (hypokalemia and urinary incontinence). There was no grade 4 toxicity. For the combined Nexrutine (R) and radiation component, no additional patients suffered a grade 3 toxicity. All the toxicities were transient. By the end of the neoadjuvant treatment, 81% of the patients had a decline in prostate-specific antigen. This is the first report of patients with prostate cancer being treated with P. amurense bark extract, and it was very well tolerated. Toxicities were minimal and self-limited. This compound can be safely used in further evaluation of a treatment effect on cancer. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Swanson, Gregory P.; Jones, William E., III; Ha, Chul S.; Jenkins, Carol A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiat Oncol, San Antonio, TX 78229 USA. [Kumar, Addanki Pratap; Basler, Joseph] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [Kumar, Addanki Pratap] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Kumar, Addanki Pratap] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA. [Swanson, Gregory P.; Jones, William E., III; Kumar, Addanki Pratap; Basler, Joseph] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Swanson, GP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Radiat Oncol, 7979 Wurzbach Rd, San Antonio, TX 78229 USA. EM swansong@uthscsa.edu FU CTRC P30 Cancer Center Support Grant from the National Cancer Institute [CA054174]; VA-Merit Award [BX 000766]; National Center for Research Resources; National Center for Advancing Translational Sciences, National Institutes of Health [1UL TR001120] FX CTRC Clinical Trial Fund: CTRC P30 Cancer Center Support Grant from the National Cancer Institute (CA054174) and VA-Merit Award BX 000766 (APK).; The project described was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant 1UL TR001120. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 13 TC 4 Z9 4 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0951-418X EI 1099-1573 J9 PHYTOTHER RES JI Phytother. Res. PD JAN PY 2015 VL 29 IS 1 BP 40 EP 42 DI 10.1002/ptr.5221 PG 3 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AZ2JP UT WOS:000348060300006 PM 25205619 ER PT J AU Harrington, RA Arena, R Despres, JP Ciarochi, A Croll, E Bloch, KD AF Harrington, Robert A. Arena, Ross Despres, Jean-Pierre Ciarochi, Amy Croll, Elizabeth Bloch, Kenneth D. CA Comm Sci Sessions Programming Amer Heart Assoc Sci Sessions 2013 Global Congress Phys Activity TI More Than 10 Million Steps in the Right Direction: Results From the First American Heart Association Scientific Sessions Walking Challenge SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Review DE American Heart Association; Walking Challenge; Physical activity ID PHYSICAL INACTIVITY; DISEASE; EXERCISE; MEDICINE; HEALTH AB In 2013, the Global Congress theme at the American Heart Association (AHA) Annual Scientific Sessions was Physical Activity (PA). As a key component of the Congress, iHealth working in collaboration with AHA provided a Bluetooth-enabled wireless PA and sleep tracker to up to 2,000 Scientific Sessions attendees. Approximately 1850 Scientific Sessions attendees registered for, received a PA tracker and participated in the Walking Challenge. More than 10 million steps were walked by participants (10,703,504) during the 2.5 days of the Walking Challenge. This translates into almost 6000 miles walked (5976.3 miles) and 656,716 calories burned by participants during the Challenge. The Global Congress of PA held at Scientific Sessions 2013 not only extensively reviewed the science of PA as a powerful/independent and, most importantly, modifiable cardiovascular risk factor, but it also provided evidence from a fun and entertaining challenge that PA as a risk behavior can be assessed and targeted. We just took 10 million steps in the right direction. Join us and make your steps count! (C) 2014 Elsevier Inc. All rights reserved. C1 [Harrington, Robert A.] Stanford Univ, Dept Med, Stanford, CA 94028 USA. [Arena, Ross] Univ Illinois, Dept Phys Therapy, Coll Appl Hlth Sci, Chicago, IL USA. [Arena, Ross] Univ Illinois, Integrat Physiol Lab, Coll Appl Hlth Sci, Chicago, IL USA. [Ciarochi, Amy] Univ Laval, Quebec City, PQ, Canada. [Despres, Jean-Pierre] Quebec Heart & Lung Inst, Quebec City, PQ, Canada. [Ciarochi, Amy; Croll, Elizabeth] Amer Heart Assoc, Dallas, TX USA. [Bloch, Kenneth D.] Harvard Univ, Sch Med, Boston, MA USA. [Bloch, Kenneth D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Harrington, RA (reprint author), Stanford Univ, Dept Med, 300 Pasteur Dr,S-102, Stanford, CA 94028 USA. EM robert.harrington@stanford.edu RI Arena, Ross/A-3141-2008 OI Arena, Ross/0000-0002-6675-1996 NR 8 TC 3 Z9 3 U1 1 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-0620 EI 1873-1740 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD JAN-FEB PY 2015 VL 57 IS 4 BP 296 EP 298 DI 10.1016/j.pcad.2014.09.009 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AZ1MU UT WOS:000348003900002 PM 25269063 ER PT J AU Tong, A Kelly, S Nusbaum, R Graves, K Peshkin, BN Valdimarsdottir, HB Wood, M McKinnon, W Garber, J McCormick, SR Jandorf, L Schwartz, MD AF Tong, Angie Kelly, Scott Nusbaum, Rachel Graves, Kristi Peshkin, Beth N. Valdimarsdottir, Heiddis B. Wood, Marie McKinnon, Wendy Garber, Judy McCormick, Shelley R. Jandorf, Lina Schwartz, Marc D. TI Intentions for risk-reducing surgery among high-risk women referred for BRCA1/BRCA2 genetic counseling SO PSYCHO-ONCOLOGY LA English DT Article DE BRCA1; BRCA2; cancer; genetic counseling; risk-reducing mastectomy; risk-reducing oophorectomy; oncology ID BREAST-CANCER RISK; CONTRALATERAL PROPHYLACTIC MASTECTOMY; BRCA2 MUTATION CARRIERS; OVARIAN-CANCER; SALPINGO-OOPHORECTOMY; BILATERAL MASTECTOMY; DECISIONAL CONFLICT; HEREDITARY BREAST; RANDOMIZED-TRIAL; FAMILY-HISTORY AB ObjectiveGenetic testing for breast and ovarian cancer susceptibility is now part of routine clinical practice. Although rates of risk-reducing surgery following genetic testing have been increasing, little is known about attitudes toward risk-reducing surgery in women prior to genetic counseling and testing. This study examines correlates of patient intentions to undergo risk-reducing mastectomy (RRM) and risk-reducing oophorectomy (RRO). MethodsParticipants were 696 women, ages 21-85, who sought breast cancer gene 1 and 2 (BRCA1/2) genetic counseling and had at least a 10% risk of carrying a mutation. The sample included women who were affected with breast or ovarian cancer and unaffected women with a known familial BRCA1/2 mutation. Participants completed a precounseling telephone questionnaire. ResultsPrior to receiving genetic counseling, 23.3% of participants were considering RRM and 42.5% were considering RRO. Variables that were independently associated with RRM intentions were cancer-specific distress (OR=1.14, 95% CI=1.03-1.26), perceived risk of breast cancer (OR=1.16, 95% CI=1.05-1.28), education (OR=1.76, 95% CI=1.03-2.99), and age (OR=0.96, 95% CI=0.95-0.98). Predictors of RRO intentions were perceived risk for ovarian cancer (OR=1.25, 95% CI=1.14-1.37), perceived risk of carrying a BRCA1/2 mutation (OR=1.74, 95% CI=1.15-2.62), marital status (OR=1.92, 95% CI=1.34-2.76), and age (OR=1.02, 95% CI=1.00-1.03). ConclusionsBecause precounseling intentions predict subsequent risk-reducing surgery decisions, this study identified patient factors associated with surgical intentions. These factors reinforce the critical role for pretest genetic counseling in communicating accurate risk estimates and management options, and addressing psychosocial concerns, to facilitate informed decision making regarding RRM and RRO. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Tong, Angie; Kelly, Scott; Nusbaum, Rachel; Graves, Kristi; Peshkin, Beth N.; Schwartz, Marc D.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Valdimarsdottir, Heiddis B.; Jandorf, Lina] MSSM, New York, NY USA. [Wood, Marie; McKinnon, Wendy] Univ Vermont, Coll Med, Familial Canc Program, Vermont Canc Ctr, Burlington, VT USA. [Garber, Judy; McCormick, Shelley R.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Schwartz, MD (reprint author), Lombardi Comprehens Canc Ctr, 3300 Whitehaven St NW,Suite 4100, Washington, DC 20007 USA. EM schwartm@georgetown.edu FU National Cancer Institute [R01 CA108933, P30 CA051008]; Jess and Mildred Fisher Center for Familial Cancer Research FX Grant support was provided by the National Cancer Institute Grants R01 CA108933, P30 CA051008, and the Jess and Mildred Fisher Center for Familial Cancer Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 47 TC 2 Z9 2 U1 3 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JAN PY 2015 VL 24 IS 1 BP 33 EP 39 DI 10.1002/pon.3560 PG 7 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA AY9TY UT WOS:000347894500005 PM 24839250 ER PT J AU Molina, Y Ceballos, RM Dolan, ED Albano, D McGregor, BA AF Molina, Yamile Ceballos, Rachel M. Dolan, Emily D. Albano, Denise McGregor, Bonnie A. TI Perceived breast cancer risk and breast cancer worry among women with a family history of breast cancer: a new perspective on coping as a mediator SO PSYCHO-ONCOLOGY LA English DT Article DE coping; distress; family history; breast cancer; risk perception C1 [Molina, Yamile; Ceballos, Rachel M.; Albano, Denise; McGregor, Bonnie A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Molina, Yamile; Ceballos, Rachel M.; Albano, Denise; McGregor, Bonnie A.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Molina, Yamile] Univ Illinois, Sch Publ Hlth, Chicago, IL USA. [Dolan, Emily D.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP McGregor, BA (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N MP900,POB 19024, Seattle, WA 98109 USA. EM bmcgrego@fhcrc.org FU National Cancer Institute [K07CA107085, P50CA148143, R25CA92408, K01CA154938-01A1] FX Data collection was supported by the National Cancer Institute (K07CA107085, P50CA148143, R25CA92408, K01CA154938-01A1). The content does not necessarily represent the official views of the National Cancer Institute/National Institutes of Health. NR 10 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JAN PY 2015 VL 24 IS 1 BP 113 EP 116 DI 10.1002/pon.3587 PG 4 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA AY9TY UT WOS:000347894500015 PM 24986795 ER PT J AU Scott, JC Matt, GE Wrocklage, KM Crnich, C Jordan, J Southwick, SM Krystal, JH Schweinsburg, BC AF Scott, J. Cobb Matt, Georg E. Wrocklage, Kristen M. Crnich, Cassandra Jordan, Jessica Southwick, Steven M. Krystal, John H. Schweinsburg, Brian C. TI A Quantitative Meta-Analysis of Neurocognitive Functioning in Posttraumatic Stress Disorder SO PSYCHOLOGICAL BULLETIN LA English DT Article DE posttraumatic stress disorder; neuropsychology; meta-analysis; memory; attention ID TRAUMATIC BRAIN-INJURY; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; CONFIRMATORY FACTOR-ANALYSIS; TEST-RETEST RELIABILITY; MAJOR DEPRESSIVE DISORDER; VERBAL-LEARNING TEST; CARD SORTING TEST; DEFICIT HYPERACTIVITY DISORDER; NEAR-INFRARED SPECTROSCOPY; CHILDHOOD SEXUAL-ABUSE AB Posttraumatic stress disorder (PTSD) is associated with regional alterations in brain structure and function that are hypothesized to contribute to symptoms and cognitive deficits associated with the disorder. We present here the first systematic meta-analysis of neurocognitive outcomes associated with PTSD to examine a broad range of cognitive domains and describe the profile of cognitive deficits, as well as modifying clinical factors and study characteristics. This report is based on data from 60 studies totaling 4,108 participants, including 1,779 with PTSD, 1,446 trauma-exposed comparison participants, and 895 healthy comparison participants without trauma exposure. Effect-size estimates were calculated using a mixed-effects meta-analysis for 9 cognitive domains: attention/working memory, executive functions, verbal learning, verbal memory, visual learning, visual memory, language, speed of information processing, and visuospatial abilities. Analyses revealed significant neurocognitive effects associated with PTSD, although these ranged widely in magnitude, with the largest effect sizes in verbal learning (d = -.62), speed of information processing (d = -.59), attention/working memory (d = -.50), and verbal memory (d = -.46). Effect-size estimates were significantly larger in treatment-seeking than community samples and in studies that did not exclude participants with attention-deficit/hyperactivity disorder, and effect sizes were affected by between-group IQ discrepancies and the gender composition of the PTSD groups. Our findings indicate that consideration of neuropsychological functioning in attention, verbal memory, and speed of information processing may have important implications for the effective clinical management of persons with PTSD. Results are further discussed in the context of cognitive models of PTSD and the limitations of this literature. C1 [Scott, J. Cobb] Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr VISN4, Philadelphia, PA 19104 USA. [Scott, J. Cobb] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Matt, Georg E.] San Diego State Univ, Dept Psychol, San Diego, CA 92182 USA. [Wrocklage, Kristen M.; Crnich, Cassandra; Jordan, Jessica; Southwick, Steven M.; Krystal, John H.; Schweinsburg, Brian C.] VA Connecticut Healthcare Syst, Natl Ctr PTSD, West Haven, CT USA. [Southwick, Steven M.; Krystal, John H.; Schweinsburg, Brian C.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. [Krystal, John H.] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06520 USA. [Krystal, John H.] Yale New Haven Med Ctr, Psychiat Serv, New Haven, CT 06504 USA. RP Scott, JC (reprint author), Philadelphia VA Med Ctr, MIRECC 116,3900 Woodland Ave, Philadelphia, PA 19104 USA. EM scott1@upenn.edu FU Department of Veterans Affairs Career Development Awards [1IK2CX000772, MH070345]; Clinical Neurosciences Division of the National Center for Posttraumatic Stress Disorder; VA National Center for PTSD; National Institute on Alcohol Abuse and Alcoholism [P50 AA012870]; National Center for Advancing Translational Sciences via Yale Center for Clinical Investigation [UL1 RR024139] FX This work was supported by Department of Veterans Affairs Career Development Awards 1IK2CX000772 to J. Cobb Scott and MH070345 to Steven M. Southwick and by the Clinical Neurosciences Division of the National Center for Posttraumatic Stress Disorder. John H. Krystal's participation was supported by the VA National Center for PTSD, the National Institute on Alcohol Abuse and Alcoholism (P50 AA012870), and the National Center for Advancing Translational Sciences via its support for the Yale Center for Clinical Investigation (UL1 RR024139). We thank Henry Kranzler for his helpful feedback on the manuscript and Blake Buss for his assistance in data entry. J. Cobb Scott presented initial results of this meta-analysis at the February 2014 meeting of the International Neuropsychological Society in Seattle, Washington. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. NR 356 TC 28 Z9 29 U1 23 U2 76 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0033-2909 EI 1939-1455 J9 PSYCHOL BULL JI Psychol. Bull. PD JAN PY 2015 VL 141 IS 1 BP 105 EP 140 DI 10.1037/a0038039 PG 36 WC Psychology; Psychology, Multidisciplinary SC Psychology GA AY6SX UT WOS:000347696900005 PM 25365762 ER PT J AU Stieg, MR Sievers, C Farr, O Stalla, GK Mantzoros, CS AF Stieg, Mareike R. Sievers, Caroline Farr, Olivia Stalla, Guenter K. Mantzoros, Christos S. TI Leptin: A hormone linking activation of neuroendocrine axes with neuropathology SO PSYCHONEUROENDOCRINOLOGY LA English DT Review DE Leptin; Neuroendocrine axes; Neuropsychiatric aspects ID METHIONYL HUMAN LEPTIN; ACTIVE ANTIRETROVIRAL THERAPY; CLINICAL-PRACTICE GUIDELINE; PITUITARY-ADRENAL AXIS; ANOREXIA-NERVOSA; HYPOTHALAMIC AMENORRHEA; PLASMA LEPTIN; SERUM LEPTIN; WEIGHT-GAIN; IN-VIVO AB Leptin, a peptide hormone secreted by adipocytes, plays a central role in controlling appetite and weight in both rodents and humans. Basic science and clinical research suggest that this hormone not only affects the regulation of the neuroendocrine axes, but also exerts effects on the central nervous system with subsequent alterations in psychological functions. For instance, leptin suppresses cortisol secretion during stress-related activation of the adrenal axis. As psychiatric disorders like depression are associated with hypercortisolism, leptin is proposed to exert anti-depressant-like effects due to its inhibition of chronically overactive hypothalamo-pituitary-adrenal axis function. Moreover, leptin status of depressed patients could serve as a prognostic marker for therapy response. Besides its influence on neuroendocrine pathways leptin seems to have direct central effects on brain development and neuroplasticity. Low leptin levels have been shown to be associated with increased risk of developing dementia, supporting the idea of a pro-cognitive effect of leptin. These areas may have direct clinical implications and deserve to be studied further in the future. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Stieg, Mareike R.; Sievers, Caroline; Stalla, Guenter K.] Max Planck Inst Psychiat, D-80804 Munich, Germany. [Farr, Olivia; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Farr, Olivia; Mantzoros, Christos S.] Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA USA. RP Stieg, MR (reprint author), Max Planck Inst Psychiat, Kreapelinstr 2-10, D-80804 Munich, Germany. EM mareike_stieg@mpipsykl.mpg.de; cmantzor@bidmc.harvard.edu OI Farr, Olivia/0000-0002-5182-3432 NR 122 TC 15 Z9 15 U1 1 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD JAN PY 2015 VL 51 BP 47 EP 57 DI 10.1016/j.psyneuen.2014.09.004 PG 11 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA AY5BI UT WOS:000347588000005 PM 25290346 ER PT J AU Slopen, N Loucks, EB Appleton, AA Kawachi, I Kubzansky, LD Non, AL Buka, S Gilman, SE AF Slopen, Natalie Loucks, Eric B. Appleton, Allison A. Kawachi, Ichiro Kubzansky, Laura D. Non, Amy L. Buka, Stephen Gilman, Stephen E. TI Early origins of inflammation: An examination of prenatal and childhood social adversity in a prospective cohort study SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE C-reactive protein; Inflammation; Prenatal exposure; Childhood adversity; Adult; Stress; Cohort study; Longitudinal ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; PSYCHOSOCIAL STRESS; CARDIOVASCULAR-DISEASE; CYTOKINE PRODUCTION; YOUNG-ADULTS; LIFE-COURSE; HPA AXIS; RISK; HEALTH AB Background: Children exposed to social adversity carry a greater risk of poor physical and mental health into adulthood. This increased risk is thought to be due, in part, to inflammatory processes associated with early adversity that contribute to the etiology of many adult illnesses. The current study asks whether aspects of the prenatal social environment are associated with levels of inflammation in adulthood, and whether prenatal and childhood adversity both contribute to adult inflammation. Methods: We examined associations of prenatal and childhood adversity assessed through direct interviews of participants in the Collaborative Perinatal Project between 1959 and 1974 with blood levels of C-reactive protein in 355 offspring interviewed in adulthood (mean age = 42.2 years). Linear and quantile regression models were used to estimate the effects of prenatal adversity and childhood adversity on adult inflammation, adjusting for age, sex, and race and other potential confounders. Results: In separate linear regression models, high levels of prenatal and childhood adversity were associated with higher CRP in adulthood. When prenatal and childhood adversity were analyzed together, our results support the presence of an effect of prenatal adversity on (log) CRP level in adulthood (beta = 0.73, 95% CI: 0.26, 1.20) that is independent of childhood adversity and potential confounding factors including maternal health conditions reported during pregnancy. Supplemental analyses revealed similar findings using quantile regression models and logistic regression models that used a clinically-relevant CRP threshold (>3 mg/L). In a fully-adjusted model that included childhood adversity, high prenatal adversity was associated with a 3-fold elevated odds (95% CI: 1.15, 8.02) of having a CRP level in adulthood that indicates high risk of cardiovascular disease. Conclusions: Social adversity during the prenatal period is a risk factor for elevated inflammation in adulthood independent of adversities during childhood. This evidence is consistent with studies demonstrating that adverse exposures in the maternal environment during gestation have lasting effects on development of the immune system. If these results reflect causal associations, they suggest that interventions to improve the social and environmental conditions of pregnancy would promote health over the life course. It remains necessary to identify the mechanisms that link maternal conditions during pregnancy to the development of fetal immune and other systems involved in adaptation to environmental stressors. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Slopen, Natalie] Univ Maryland, Sch Publ Hlth, Dept Epidemiol & Biostat, College Pk, MD 20742 USA. [Loucks, Eric B.; Buka, Stephen] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA. [Appleton, Allison A.] SUNY Albany, Dept Epidemiol & Biostat, Sch Publ Hlth, Rensselaer, NY USA. [Kawachi, Ichiro; Kubzansky, Laura D.; Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Non, Amy L.] Vanderbilt Univ, Dept Anthropol, Nashville, TN 37235 USA. [Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Gilman, Stephen E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Slopen, N (reprint author), Univ Maryland, Sch Publ Hlth, Dept Epidemiol & Biostat, College Pk, MD 20742 USA. EM nslopen@umd.edu RI Gilman, Stephen/E-7632-2010 OI Gilman, Stephen/0000-0002-8331-6419 FU National Institutes of Health [MH087544, AG023397]; Robert Wood Johnson Foundation (RWJF) [67751]; W. K. Kellogg Foundation [P3022586] FX This research was supported by grants from the National Institutes of Health (MH087544, PI: Gilman; AG023397, PI: Buka), the Robert Wood Johnson Foundation (RWJF ID #67751), and the W. K. Kellogg Foundation (P3022586). We appreciate the contributions of Ms. Kathleen McGaffigan, our expert analyst and data manager. NR 56 TC 7 Z9 7 U1 5 U2 28 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD JAN PY 2015 VL 51 BP 403 EP 413 DI 10.1016/j.psyneuen.2014.10.016 PG 11 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA AY5BI UT WOS:000347588000037 PM 25462912 ER PT J AU Nievergelt, CM Maihofer, AX Mustapic, M Yurgil, KA Schork, NJ Miller, MW Logue, MW Geyer, MA Risbrough, VB O'Connor, DT Baker, DG AF Nievergelt, Caroline M. Maihofer, Adam X. Mustapic, Maja Yurgil, Kate A. Schork, Nicholas J. Miller, Mark W. Logue, Mark W. Geyer, Mark A. Risbrough, Victoria B. O'Connor, Daniel T. Baker, Dewleen G. TI Genomic predictors of combat stress vulnerability and resilience in US Marines: A genome-wide association study across multiple ancestries implicates PRTFDC1 as a potential PTSD gene SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE GWAS; Meta-analysis; PTSD; Ancestry; Polygenic risk score; Trauma; GxE; Bipolar disorder; Pleiotropy ID 2 INDEPENDENT SAMPLES; MULTILOCUS GENOTYPE DATA; ENVIRONMENT INTERACTION; PSYCHIATRIC-DISORDERS; MAJOR DEPRESSION; TRANSPORTER GENE; COMPLEX TRAITS; RISK; SYMPTOMS; POLYMORPHISMS AB Background: Research on the etiology of post-traumatic stress disorder (PTSD) has rapidly matured, moving from candidate gene studies to interrogation of the entire human genome in genome-wide association studies (GWAS). Here we present the results of a GWAS performed on samples from combat-exposed U.S. Marines and Sailors from the Marine Resiliency Study (MRS) scheduled for deployment to Iraq and/or Afghanistan. The MRS is a large, prospective study with longitudinal follow-up designed to identify risk and resiliency factors for combat-induced stress-related symptoms. Previously implicated PTSD risk loci from the literature and polygenic risk scores across psychiatric disorders were also evaluated in the MRS cohort. Methods: Participants (N=3494) were assessed using the Clinician-Administered PTSD Scale and diagnosed using the DSM-IV diagnostic criterion. Subjects with partial and/or full PTSD diagnosis were called cases, all other subjects were designated controls, and study-wide maximum CAPS scores were used for longitudinal assessments. Genomic DNA was genotyped on the It lumina HumanOmniExpressExome array. Individual genetic ancestry was determined by supervised cluster analysis for subjects of European, African, Hispanic/Native American, and other descent. To test for association of SNPs with PTSD, logistic regressions were performed within each ancestry group and results were combined in meta-analyses. Measures of childhood and adult trauma were included to test for gene-by-environment (GxE) interactions. Polygenic risk scores from the Psychiatric Genomic Consortium were used for major depressive disorder (MDD), bipolar disorder (BPD), and schizophrenia (SCZ). Results: The array produced >800 K directly genotyped and >21M imputed markers in 3494 unrelated, trauma-exposed males, of which 940 were diagnosed with partial or full PTSD. The GWAS meta-analysis identified the phosphoribosyl transferase domain containing 1 gene (PRTFDC1) as a genome-wide significant PTSD locus (rs6482463; OR = 1.47, SE = 0.06, p = 2.04 x 10(-9)), with a similar effect across ancestry groups. Association of PRTFDC1 with PTSD in an independent military cohort showed some evidence for replication. Loci with suggestive evidence of association (n = 25 genes, p < 5 x 10(-6)) further implicated genes related to immune response and the ubiquitin system, but these findings remain to be replicated in larger GWASs. A replication analysis of 25 putative PTSD genes from the literature found nominally significant SNPs for the majority of these genes, but associations did not remain significant after correction for multiple comparison. A cross-disorder analysis of polygenic risk scores from GWASs of BPD, MDD, and SCZ found that PTSD diagnosis was associated with risk sores of BPD, but not with MDD or SCZ. Conclusions: This first multi-ethnic/racial GWAS of PTSD highlights the potential to increase power through meta-analyses across ancestry groups. We found evidence for PRTFDC1 as a potential novel PTSD gene, a finding that awaits further replication. Our findings indicate that the genetic architecture of PTSD may be determined by many SNPs with small effects, and overlap with other neuropsychiatric disorders, consistent with current findings from large GWAS of other psychiatric disorders. (C) 2014 Published by Elsevier Ltd. C1 [Nievergelt, Caroline M.; Maihofer, Adam X.; Mustapic, Maja; Risbrough, Victoria B.; Baker, Dewleen G.] Univ Calif San Diego, Sch Med, Dept Psychiat, La Jolla, CA 92093 USA. [Mustapic, Maja; O'Connor, Daniel T.] Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 USA. [Schork, Nicholas J.] J Craig Venter Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. [Nievergelt, Caroline M.; Yurgil, Kate A.; Risbrough, Victoria B.; Baker, Dewleen G.] VA San Diego Healthcare Syst, VA Ctr Excellence Stress & Mental Hlth CESAMH, La Jolla, CA 92161 USA. [Miller, Mark W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Miller, Mark W.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Logue, Mark W.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Logue, Mark W.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. RP Nievergelt, CM (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM cnievergelt@ucsd.edu RI Miller, Mark/G-7322-2011; OI Miller, Mark/0000-0001-6393-8563; Nievergelt, Caroline/0000-0001-5766-8923 FU NIH [1 R01MH093500, 1 U01 MH092758, R01MH079806]; Marine Corps and Navy Bureau of Medicine and Surgery (BUMED); VA Health Services and Development (HSRD); Marine Corps; BUMED; VA [5I01CX000431-02] FX CMN is supported by NIH grants 1 R01MH093500, 1 U01 MH092758, and by the Marine Corps and Navy Bureau of Medicine and Surgery (BUMED). VA Health Services and Development (HSR&D), the Marine Corps, and BUMED provided funding for MRS-I and MRS-II (DGB, NJS, DTO, MAG, VBR, MRS Team). The VA dataset was supported by NIH grant R01MH079806 and VA grant 5I01CX000431-02 to MWM. NR 68 TC 29 Z9 29 U1 14 U2 31 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD JAN PY 2015 VL 51 BP 459 EP 471 DI 10.1016/j.psyneuen.2014.10.017 PG 13 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA AY5BI UT WOS:000347588000043 PM 25456346 ER PT J AU O'Donovan, A Chao, LL Paulson, J Samuelson, KW Shigenaga, JK Grunfeld, C Weiner, MW Neylan, TC AF O'Donovan, Aoife Chao, Linda L. Paulson, Jennifer Samuelson, Kristin W. Shigenaga, Judy K. Grunfeld, Cart Weiner, Mike W. Neylan, Thomas C. TI Altered inflammatory activity associated with reduced hippocampal volume and more severe posttraumatic stress symptoms in Gulf War veterans SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Hippocampus; Inflammation; Posttraumatic stress disorder; Structural magnetic resonance imaging; Trauma; Veterans ID C-REACTIVE PROTEIN; MAJOR DEPRESSIVE DISORDER; DECLARATIVE MEMORY; CHRONIC NEURODEGENERATION; ELEVATED INFLAMMATION; PSYCHOLOGICAL STRESS; CHILDHOOD TRAUMA; BRAIN; PTSD; INTERLEUKIN-6 AB Background: Inflammation may reduce hippocampal volume by blocking neurogenesis and promoting neurodegeneration. Posttraumatic stress disorder (PTSD) has been linked with both elevated inflammation and reduced hippocampal volume. However, few studies have examined associations between inflammatory markers and hippocampal volume, and none have examined these associations in the context of PTSD. Methods: We measured levels of the inflammatory markers interleukin-6 (IL-6) and soluble receptor II for tumor necrosis factor (sTNF-RII) as well as hippocampal volume in 246 Gulf War veterans with and without current and past PTSD as assessed with the Clinician Administered PTSD Scale (CAPS). Enzyme-linked immunosorbent assays were used to measure inflammatory markers, and 1.5 Testa magnetic resonance imaging (MRI) and Freesurfer version 4.5 were used to quantify hippocampal volume. Hierarchical linear regression and analysis of covariance models were used to examine if hippocampal volume and PTSD status would be associated with elevated levels of IL-6 and sTNF-RII. Results: Increased sTNF-RII, but not IL-6, was significantly associated with reduced hippocampal volume (beta = -0.14, p = 0.01). The relationship between sTNF-RII and hippocampal volume was independent of potential confounds and covariates, including PTSD status. Although we observed no PTSD diagnosis-related differences in either IL-6 or sTNF-RII, higher PTSD severity was associated with significantly increased sTNF-RII (beta = 0.24, p = 0.04) and reduced IL-6 levels (beta = 0.24, p = 0.04). Conclusions: Our results indicate that specific inflammatory proteins may be associated with brain structure and function as indexed by hippocampal volume and PTSD symptoms. (C) 2014 Published by Elsevier Ltd. C1 [O'Donovan, Aoife; Chao, Linda L.; Paulson, Jennifer; Shigenaga, Judy K.; Grunfeld, Cart; Weiner, Mike W.; Neylan, Thomas C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [O'Donovan, Aoife; Chao, Linda L.; Paulson, Jennifer; Samuelson, Kristin W.; Shigenaga, Judy K.; Grunfeld, Cart; Weiner, Mike W.; Neylan, Thomas C.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [O'Donovan, Aoife; Chao, Linda L.; Paulson, Jennifer; Samuelson, Kristin W.; Shigenaga, Judy K.; Grunfeld, Cart; Weiner, Mike W.; Neylan, Thomas C.] Northern Calif Inst Res & Educ, San Francisco, CA USA. [Paulson, Jennifer; Samuelson, Kristin W.] Alliant Int Univ, Calif Sch Profess Psychol, Alhambra, CA 91803 USA. RP O'Donovan, A (reprint author), San Francisco VA Med Ctr, 4150 Clement St,116-C1, San Francisco, CA 94121 USA. EM Aoife.ODonovan@ucsf.edu FU Lightfighter Foundation; US Army Military Operational Medicine Research Program, Department of Defense [W81XWH-11-2-0189]; Mental Illness Research and Education Clinical Center (MIRECC) of the U.S. Veterans Health Administration; National Institute on Aging [K24 AG031155]; National Center for Advancing Translational Sciences Career Development Award [KL2 TR000143]; Society in Science-Branco Weiss Fellowship FX This study was generously supported by grants from the Lightfighter Foundation, the US Army Military Operational Medicine Research Program, Department of Defense W81XWH-11-2-0189 entitled, "Investigation of Links Between PTSD and Dementia," awarded to the Northern California Institute for Research and the Mental Illness Research and Education Clinical Center (MIRECC) of the U.S. Veterans Health Administration and the National Institute on Aging (K24 AG031155) as well as by a National Center for Advancing Translational Sciences Career Development Award (KL2 TR000143) and a Society in Science-Branco Weiss Fellowship (to AOD). Resources and the use of facilities were provided by the Veterans Administration Medical Center, San Francisco, California. This manuscript's contents are solely the responsibility of the authors and do not necessarily represent the official views of any of the funding bodies. The authors thank Jennifer Hlavin, Mark Pacult, Natasha Sukerkar, and Kevin Kim for assistance with this study and manuscript. NR 65 TC 11 Z9 11 U1 7 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD JAN PY 2015 VL 51 BP 557 EP 566 DI 10.1016/j.psyneuen.2014.11.010 PG 10 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA AY5BI UT WOS:000347588000051 PM 25465168 ER PT J AU Bierer, LM Ivanov, I Carpenter, DM Wong, EW Golier, JA Tang, CY Yehuda, R AF Bierer, Linda M. Ivanov, Iliyan Carpenter, David M. Wong, Edmund W. Golier, Julia A. Tang, Cheuk Y. Yehuda, Rachel TI White matter abnormalities in Gulf War veterans with posttraumatic stress disorder: A pilot study SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE PTSD; DTI; Diffusion tensor imaging; White matter; Gulf War veterans; Connectivity; Cingulum bundle ID MEDIAL PREFRONTAL CORTEX; SCRIPT-DRIVEN IMAGERY; DIFFUSION TENSOR; ANTERIOR CINGULATE; ACTION-POTENTIALS; NEURAL-NETWORKS; BLOOD-FLOW; PTSD; INTEGRITY; AMYGDALA AB Background: Gulf War veterans were exposed to environmental toxins not present in other combat theaters resulting in a unique biological signature that only partially resembles that seen in other combat veterans with PTSD. Thus it is important to determine if brain abnormalities seen in non-Gulf War veterans with PTSD are also present in Gulf War veterans. In this pilot study, diffusion tensor imaging (DTI) tractography was used to assess the ultra-structural integrity of fronto-limbic white matter connections in Gulf War veterans with and without PTSD. The effects of chronic multisymptom illness on DTI measures was also evaluated. Methods: Subjects were 20 previously studied Gulf War veterans on whom MRIs had been obtained. Mean diffusivity (MD) and fractional anisotropy (FA) were determined for left and right cingulum bundle by DTI tractography and compared in separate analyses for 12 veterans with, and 8 without PTSD. The effect of chronic multisymptom illness and it's interaction with PTSD, were similarly investigated using multivariate ACOVA. Partial correlations were used to test the associations of both DTI indices with PTSD severity and plasma cortisol, controlling for whole brain volume. Results: Significantly lower MD was demonstrated in the right cingulum bundle among Gulf War veterans with PTSD. There were no significant differences in MD or FA in the left cingulum bundle. The presence of chronic multisymptom illness significantly attenuated the PTSD associated decrement in right cingulum MD. Clinician and self-rated PTSD symptom severity scores were significantly associated with reduced MD and increased FA in the right cingulum. Similar associations were observed for 8am plasma cortisol in a subset of participants. Conclusions: The preliminary findings indicate increased structural integrity supporting enhanced connectivity - between right amygdala and anterior cingulate cortex in PTSD. This effect was strongest among Gulf War veterans without chronic multisymptom illness. The association of both MD and FA in the right cingulum with PTSD severity, and with heightened glucocorticoid responsivity, suggests that these DTI findings are a reflection of current PTSD illness expression. Although based on a small sample, these microstructural observations are consistent with a functional model suggesting increased amygdala responsivity in association with anterior cingulate modulation in PTSD. (C) 2014 Published by Elsevier Ltd. C1 [Bierer, Linda M.; Ivanov, Iliyan; Golier, Julia A.; Yehuda, Rachel] Icahn Sch Med Mt Sinai, Dept Psychiat, Traumat Stress Studies Div, New York, NY 10029 USA. [Bierer, Linda M.; Ivanov, Iliyan; Golier, Julia A.; Yehuda, Rachel] James J Peters VA Med Ctr, Traumat Stress Studies Div, Bronx, NY 10468 USA. [Carpenter, David M.; Wong, Edmund W.; Tang, Cheuk Y.] Icahn Sch Med Mt Sinai, Dept Radiol, New York, NY 10029 USA. RP Bierer, LM (reprint author), James J Peters VAMC, OOMH, 116-A,130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM Linda.Bierer@va.gov FU VA MERIT entitled "Glucocorticoid Responsivity in Gulf War Veterans"; National Center for Research Resources, National Institutes of Health [5 MO1 RR00071] FX This work was supported principally by a VA MERIT entitled "Glucocorticoid Responsivity in Gulf War Veterans." In addition, partial support was obtained through a grant (5 MO1 RR00071) to the Mount Sinai General Clinical Research Center from the National Center for Research Resources, National Institutes of Health. NR 71 TC 2 Z9 3 U1 5 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD JAN PY 2015 VL 51 BP 567 EP 576 DI 10.1016/j.psyneuen.2014.11.007 PG 10 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA AY5BI UT WOS:000347588000052 PM 25465169 ER PT J AU Neumeister, A Seidel, J Ragen, BJ Pietrzak, RH AF Neumeister, Alexander Seidel, Jordan Ragen, Benjamin J. Pietrzak, Robert H. TI Translational evidence for a role of endocannabinoids in the etiology and treatment of posttraumatic stress disorder SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE PTSD; Endocannabinoids; 5-Factor PTSD model; Anxious arousal; Treatment ID VENLAFAXINE EXTENDED-RELEASE; CHRONIC UNPREDICTABLE STRESS; RANDOMIZED CONTROLLED-TRIAL; NATIONAL COMORBIDITY SURVEY; QUALITY-OF-LIFE; GENDER-DIFFERENCES; CANNABINOID RECEPTORS; HIPPOCAMPAL CB1; 5-FACTOR MODEL; PTSD SYMPTOMS AB Introduction: Posttraumatic stress disorder (PTSD) is a prevalent, chronic, and disabling anxiety disorder that may develop following exposure to a traumatic event. Despite the public health significance of PTSD, relatively little is known about the etiology or pathophysiology of this disorder, and pharmacotherapy development to date has been largely opportunistic instead of mechanism-based. Recently, an accumulating body of evidence has implicated the endocannabinoid system in the etiology of PTSD, and targets within this system are believed to be suitable for treatment development. Methods: Herein, we describe evidence from translational studies arguing for the relevance of the endocannabinoid system in the etiology of PTSD. We also show mechanisms relevant for treatment development. Results: There is convincing evidence from multiple studies for reduced endocannabinoid availability in PTSD. Brain imaging studies show molecular adaptations with elevated cannabinoid type 1 (CB1) receptor availability in PTSD which is linked to abnormal threat processing and anxious arousal symptoms. Conclusion: Of particular relevance is evidence showing reduced levels of the endocannabinoid anandamide and compensatory increase of CB1 receptor availability in PTSD, and an association between increased CB1 receptor availability in the amygdala and abnormal threat processing, as well as increased severity of hyperarousal, but not dysphoric symptomatology, in trauma survivors. Given that hyperarousal symptoms are the key drivers of more disabling aspects of PTSD such as emotional numbing or suicidality, novel, mechanism-based pharmacotherapies that target this particular symptom cluster in patients with PTSD may have utility in mitigating the chronicity and morbidity of the disorder. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Neumeister, Alexander; Seidel, Jordan; Ragen, Benjamin J.] NYU, Sch Med, Dept Psychiat, New York, NY 10016 USA. [Neumeister, Alexander] NYU, Sch Med, Dept Radiol, New York, NY 10016 USA. [Pietrzak, Robert H.] VA Connecticut Healthcare Syst, US Dept Vet Affairs, Natl Ctr Posttraumat Stress Disorder, Clin Neurosci Div, West Haven, CT USA. [Pietrzak, Robert H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. RP Neumeister, A (reprint author), NYU, Sch Med, Mol Imaging Program Anxiety & Mood Disorders, One Pk Ave,8th Floor,Room 225, New York, NY 10016 USA. EM alexander.neumeister@nyumc.org FU National Institutes of Health (NIH) [R21MH096105, R21MH085627, RO1MH096876, R01MH102566]; Office of the Assistant Secretary of Defense for Health Affairs [W81XWH-14-1-0084]; Pfizer, Inc.; Lilly, Inc. FX This project was supported by the National Institutes of Health (NIH) through the following awards: R21MH096105, R21MH085627, RO1MH096876 and R01MH102566; the Office of the Assistant Secretary of Defense for Health Affairs under Award No. W81XWH-14-1-0084. The Clinical Neurosciences Division of the United States Department of Veterans Affairs National Center for Posttraumatic Stress Disorder. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense, the NIH or VA.; Dr. Neumeister has received consulting fees from Pfizer, Inc. This activity is unrelated to the present publication. Dr. Neumeister has received grant support from Lilly, Inc. which is unrelated to the present publication. Dr. Pietrzak is a scientific consultant to Cogstate, Ltd. and this activity is unrelated to the present report. NR 84 TC 14 Z9 14 U1 4 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD JAN PY 2015 VL 51 BP 577 EP 584 DI 10.1016/j.psyneuen.2014.10.012 PG 8 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA AY5BI UT WOS:000347588000053 PM 25456347 ER PT J AU Yehuda, R Bierer, LM Pratchett, LC Lehrner, A Koch, EC Van Manen, JA Flory, JD Makotkine, I Hildebrandt, T AF Yehuda, Rachel Bierer, Linda M. Pratchett, Laura C. Lehrner, Amy Koch, Erin C. Van Manen, Jaklyn A. Flory, Janine D. Makotkine, Iouri Hildebrandt, Tom TI Cortisol augmentation of a psychological treatment for warfighters with posttraumatic stress disorder: Randomized trial showing improved treatment retention and outcome SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE PTSD; Prolonged exposure; Hydrocortisone; Pharmacological augmentation strategies; Psychotherapy; Glucocorticoid receptor; Veterans; Treatment outcome ID PROLONGED EXPOSURE THERAPY; BASOLATERAL AMYGDALA; CONDITIONED FEAR; GLUCOCORTICOID ENHANCEMENT; NORADRENERGIC ACTIVATION; MEMORY; RATS; PTSD; EXTINCTION; RETRIEVAL AB Background: Prolonged exposure (PE) therapy for post-traumatic stress disorder (PTSD) in military veterans has established efficacy, but is ineffective for a substantial number of patients. PE is also associated with high dropout rates. We hypothesized that hydrocortisone augmentation would enhance symptom improvement and reduce drop-out rates by diminishing the distressing effects of traumatic memories retrieved during imaginal exposure. We also hypothesized that in responders, hydrocortisone augmentation would be more effective in reversing glucocorticoid indices associated with PTSD than placebo augmentation. Method: Twenty-four veterans were randomized to receive either 30 mg oral hydrocortisone or placebo prior to PE sessions 3-10 in a double-blind protocol. Glucocorticoid receptor sensitivity was assessed in cultured peripheral blood mononuclear cells (PBMC) using the in vitro lysozyme inhibition test and was determined before and after treatment. Intent-to-treat analysis was performed using latent growth curve modeling of treatment effects on change in PTSD severity over time. Veterans who no longer met diagnostic criteria for PTSD at post-treatment were designated as responders. Results: Veterans randomized to hydrocortisone or placebo augmentation did not differ significantly in clinical severity or glucocorticoid sensitivity at pre-treatment. Hydrocortisone augmentation was associated with greater reduction in total PTSD symptoms compared to placebo, a finding that was explained by significantly greater patient retention in the hydrocortisone augmentation condition. A significant treatment condition by responder status interaction for glucocorticoid sensitivity indicated that responders to hydrocortisone augmentation had the highest pre-treatment glucocorticoid sensitivity (lowest lysozyme IC50-DEX) that diminished over the course of treatment. There was a significant association between decline in glucocorticoid responsiveness and improvement in PTSD symptoms among hydrocortisone recipients. Conclusions: The results of this pilot study suggest that hydrocortisone augmentation of PE may result in greater retention in treatment and thereby promote PTSD symptom improvement. Further, the results suggest that particularly elevated glucocorticoid responsiveness at pre-treatment may identify veterans likely to respond to PE combined with an intervention that targets glucocorticoid sensitivity. Confirmation of these findings will suggest that pharmacologic interventions that target PTSD-associated glucocorticoid dysregulation may be particularly helpful in promoting a positive clinical response to PTSD psychotherapy. Published by Elsevier Ltd. C1 [Yehuda, Rachel; Bierer, Linda M.; Pratchett, Laura C.; Lehrner, Amy; Koch, Erin C.; Van Manen, Jaklyn A.; Flory, Janine D.; Makotkine, Iouri] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Yehuda, Rachel; Bierer, Linda M.; Pratchett, Laura C.; Lehrner, Amy; Flory, Janine D.; Makotkine, Iouri; Hildebrandt, Tom] Icahn Sch Med Mt Sinai, Dept Psychiat, Traumat Stress Studies Div, New York, NY 10029 USA. RP Yehuda, R (reprint author), James J Peters VA Med Ctr, OOMH, 116-A,130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM Rachel.yehuda@va.gov OI Hildebrandt, Thomas/0000-0001-7054-9590 FU Lightfighters Trust Foundation [LFT2009-02-1]; Department of Defense (DOD) [W81XWH-10-2-0072] FX This work was supported by a grant from the Lightfighters Trust Foundation (LFT2009-02-1) entitled, 'Cortisol augmentation of a psychological treatment in warfighters with PTSD.'; Additional support received from a grant from the Department of Defense (DOD W81XWH-10-2-0072) entitled, 'Improving PTSD outcomes in OIF/OEF returnees: A randomized clinical trial of hydrocortisone augmentation of prolonged exposure therapy.' NR 48 TC 21 Z9 21 U1 3 U2 24 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD JAN PY 2015 VL 51 BP 589 EP 597 DI 10.1016/j.psyneuen.2014.08.004 PG 9 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA AY5BI UT WOS:000347588000055 PM 25212409 ER PT J AU Jussila, K Kuusikko-Gauffin, S Mattila, ML Loukusa, S Pollock-Wurman, R Joskitt, L Ebeling, H Moilanen, I Pauls, D Hurtig, T AF Jussila, Katja Kuusikko-Gauffin, Sanna Mattila, Marja-Leena Loukusa, Soile Pollock-Wurman, Rachel Joskitt, Leena Ebeling, Hanna Moilanen, Irma Pauls, David Hurtig, Tuula TI Cross-cultural differences in the Parent Rated Social Responsiveness Scale (SRS)? Evaluation of the Finnish version among high-functioning school aged males with and without autism spectrum disorder SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorder; Social reciprocity; Social Responsiveness Scale; Cross-cultural differences; Screening ID COMMUNICATION-SKILLS; TOTAL POPULATION; TRAITS; VALIDATION; VALIDITY; BEHAVIOR; CHILDREN; TWIN AB When importing screening questionnaires of ASD, it has been found that parental interpretation/reporting of autistic traits may be culturally influenced. In the current study, our aim was preliminary evaluation of the Finnish parent rated SRS in order to determine whether the measure would show promise as an aid in screening. The study sample consisted of high-functioning school aged male ASD outpatients of Oulu University Hospital (n = 44, age 11.4 +/- 2.3) and age-matched controls (n = 44, age 11.8 +/- 2.4 years). Internal consistency as well as convergent and discriminative validity was in line with previous research. However, the results indicated that the cut-off published in the SRS manual might be too high to be used in Finland. Our results emphasize the importance of determining the normative range and clinical cut-offs in various cultures when importing diagnostic screening questionnaires in order to avoid getting high percentages of false negatives in the screening phase, and thus risk leaving many children without adequate diagnostic evaluation and rehabilitation.(C) 2014 Elsevier Ltd. All rights reserved. C1 [Jussila, Katja; Kuusikko-Gauffin, Sanna; Mattila, Marja-Leena; Ebeling, Hanna; Moilanen, Irma; Hurtig, Tuula] Oulu Univ Hosp, Dept Child Psychiat, Oulu, Finland. [Jussila, Katja; Kuusikko-Gauffin, Sanna; Mattila, Marja-Leena; Ebeling, Hanna; Moilanen, Irma; Hurtig, Tuula] Univ Oulu, SF-90100 Oulu, Finland. [Loukusa, Soile] Univ Oulu, Child Language Res Ctr, Fac Humanities, SF-90100 Oulu, Finland. [Pollock-Wurman, Rachel] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. [Joskitt, Leena] Univ Hosp Oulu, Dept Child Psychiat, Oulu, Finland. [Pauls, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit,Ctr Human Genet, Cambridge, MA 02138 USA. [Hurtig, Tuula] Univ Oulu, Inst Hlth Sci, SF-90100 Oulu, Finland. [Hurtig, Tuula] Univ Oulu, Dept Psychiat, SF-90100 Oulu, Finland. RP Jussila, K (reprint author), Oulu Univ Hosp, Dept Child Psychiat, Oulu, Finland. EM katja.jussila@oulu.fi NR 29 TC 1 Z9 1 U1 5 U2 17 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1750-9467 EI 1878-0237 J9 RES AUTISM SPECT DIS JI Res. Autism Spectr. Disord. PD JAN PY 2015 VL 9 BP 38 EP 44 DI 10.1016/j.rasd.2014.09.008 PG 7 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AY5GS UT WOS:000347601500006 ER PT J AU Waye, C Wong, M Lee, S AF Waye, Courtney Wong, Mark Lee, Shuko TI Implementation of a CIWA-Ar Alcohol Withdrawal Protocol in a Veterans Hospital SO SOUTHERN MEDICAL JOURNAL LA English DT Article DE alcohol-withdrawal syndrome; alcohol detoxification; Clinical Institute Withdrawal Assessment for Alcohol Scale; fixed-dose benzodiazepine; revised; symptom-triggered benzodiazepine ID SCALE; MANAGEMENT AB Objectives The South Texas Veterans Health Care System (STVHCS) implemented a Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar)-based alcohol-withdrawal protocol in June 2013. The aim of this study was to determine the efficacy and safety of the new protocol. The primary objective was the evaluation of whether implementation of the CIWA-Ar alcohol-withdrawal protocol decreased the average length of hospital stay for patients admitted with alcohol withdrawal syndrome (AWS) as compared with treatment before the introduction of the protocol. Secondary endpoints evaluated benzodiazepine (BZD)-prescribing practices, use of adjunctive medications for AWS, and safety outcomes. Methods We reviewed 748 admissions with documented AWS or alcohol-related diagnoses during the study periods of July 2012 to December 2012 (preprotocol) and July 2013 to December 2013 (postprotocol). Patients in the preprotocol group needed to have a scheduled dose of a BZD in the electronic medical record, and those assigned to the postprotocol group needed to have at least one documented CIWA-Ar note in their electronic medical record. Exclusion criteria included prior conditions that interfered with accurate treatment of alcohol withdrawal. Results There were no statistical differences in baseline characteristics between groups. No difference was found in the primary endpoint of length of stay when comparing hospitalizations pre- and postprotocol implementation (3.84 2.31 days vs 3.82 +/- 2.7 days; P = 0.667). There was no statistical significance in total cumulative dose of BZD, daily dose of BZD, or duration of BZD use when compared pre- and postprotocol. No safety events requiring further intervention occurred. Conclusions Implementation of a CIWA-Ar protocol at our institution did not result in a decreased duration of hospital stay; however, a decline in prescribing fixed-schedule BZDs was documented. C1 South Texas Vet Hlth Care Syst, Serv Pharm, San Antonio, TX 78229 USA. Univ Texas Hlth Sci Ctr San Antonio, Pharmacotherapy Educ Res Ctr, San Antonio, TX 78229 USA. Univ Texas Austin, Pharmacotherapy Div, Coll Pharm, Austin, TX 78712 USA. South Texas Vet Hlth Care Syst, Res & Dev, San Antonio, TX 78229 USA. RP Waye, C (reprint author), South Texas Vet Hlth Care Syst, 7400 Merton Minter Blvd 119, San Antonio, TX 78229 USA. EM courtney.waye@va.gov NR 16 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0038-4348 EI 1541-8243 J9 SOUTH MED J JI South.Med.J. PD JAN PY 2015 VL 108 IS 1 BP 23 EP 28 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA AZ0QJ UT WOS:000347949500006 PM 25580753 ER PT J AU Hunt, DP AF Hunt, Daniel P. TI Commentary on "No to Greed'' SO SOUTHERN MEDICAL JOURNAL LA English DT Editorial Material ID HEPATITIS-C; INFECTION C1 [Hunt, Daniel P.] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Inpatient Clinician Educ Serv,Dept Med, Boston, MA USA. RP Hunt, DP (reprint author), Massachusetts Gen Hosp, Inpatient Clinician Educ Serv, 50 Staniford St,Suite 503B, Boston, MA 02114 USA. EM dphunt@partners.org NR 8 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0038-4348 EI 1541-8243 J9 SOUTH MED J JI South.Med.J. PD JAN PY 2015 VL 108 IS 1 BP 65 EP 66 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AZ0QJ UT WOS:000347949500015 PM 25580762 ER PT J AU Eikermann-Haerter, K Lee, JH Yalcin, N Yu, ES Daneshmand, A Wei, Y Zheng, Y Can, A Sengul, B Ferrari, MD van den Maagdenberg, AMJM Ayata, C AF Eikermann-Haerter, Katharina Lee, Jeong Hyun Yalcin, Nilufer Yu, Esther S. Daneshmand, Ali Wei, Ying Zheng, Yi Can, Anil Sengul, Buse Ferrari, Michel D. van den Maagdenberg, Arn M. J. M. Ayata, Cenk TI Migraine Prophylaxis, Ischemic Depolarizations, and Stroke Outcomes in Mice SO STROKE LA English DT Article DE cortical spreading depression; lamotrigine; middle cerebral artery occlusion; migraine; prophylaxis; stroke; topiramate ID CORTICAL SPREADING DEPRESSION; RANDOMIZED CONTROLLED-TRIAL; ANTIEPILEPTIC DRUGS; IN-VITRO; PERIINFARCT DEPOLARIZATIONS; BRAIN-INJURY; TOPIRAMATE; SUSCEPTIBILITY; LAMOTRIGINE; NEUROPROTECTION AB Background and Purpose-Migraine with aura is an established stroke risk factor, and excitatory mechanisms such as spreading depression (SD) are implicated in the pathogenesis of both migraine and stroke. Spontaneous SD waves originate within the peri-infarct tissue and exacerbate the metabolic mismatch during focal cerebral ischemia. Genetically enhanced SD susceptibility facilitates anoxic depolarizations and peri-infarct SDs and accelerates infarct growth, suggesting that susceptibility to SD is a critical determinant of vulnerability to ischemic injury. Because chronic treatment with migraine prophylactic drugs suppresses SD susceptibility, we tested whether migraine prophylaxis can also suppress ischemic depolarizations and improve stroke outcome. Methods-We measured the cortical susceptibility to SD and ischemic depolarizations, and determined tissue and neurological outcomes after middle cerebral artery occlusion in wild-type and familial hemiplegic migraine type 1 knock-in mice treated with vehicle, topiramate or lamotrigine daily for 7 weeks or as a single dose shortly before testing. Results-Chronic treatment with topiramate or lamotrigine reduced the susceptibility to KCl-induced or electric stimulation-induced SDs as well as ischemic depolarizations in both wild-type and familial hemiplegic migraine type 1 mutant mice. Consequently, both tissue and neurological outcomes were improved. Notably, treatment with a single dose of either drug was ineffective. Conclusions-These data underscore the importance of hyperexcitability as a mechanism for increased stroke risk in migraineurs, and suggest that migraine prophylaxis may not only prevent migraine attacks but also protect migraineurs against ischemic injury. C1 [Eikermann-Haerter, Katharina; Lee, Jeong Hyun; Yalcin, Nilufer; Yu, Esther S.; Daneshmand, Ali; Wei, Ying; Zheng, Yi; Can, Anil; Sengul, Buse; Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurovasc Res Lab,Dept Radiol, Charlestown, MA USA. [Ferrari, Michel D.; van den Maagdenberg, Arn M. J. M.] Leiden Univ, Med Ctr, Dept Neurol, NL-2300 RA Leiden, Netherlands. [van den Maagdenberg, Arn M. J. M.] Leiden Univ, Med Ctr, Dept Human Genet, NL-2300 RA Leiden, Netherlands. [Ayata, Cenk] Harvard Univ, Sch Med, Dept Neurol, Stroke Serv,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Ayata, Cenk] Harvard Univ, Sch Med, Dept Neurol, Neurosci Intens Care Unit,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Ayata, C (reprint author), Massachusetts Gen Hosp, Stroke & Neurovasc Regulat 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 [NS061505, NS055104, NS35611, P01 NS035611, P01 NS055104, R01 NS061505] NR 44 TC 12 Z9 12 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD JAN PY 2015 VL 46 IS 1 BP 229 EP 236 DI 10.1161/STROKEAHA.114.006982 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AX1XB UT WOS:000346735800050 PM 25424478 ER PT J AU Majersik, JJ Cole, JW Golledge, J Rost, NS Chan, YFY Gurol, ME Lindgren, AG Woo, D Fernandez-Cadenas, I Chen, DT Thijs, V Worrall, BB Kamal, A Bentley, P Wardlaw, JM Ruigrok, YM Battey, TWK Schmidt, R Montaner, J Giese, AK Roquer, J Jimenez-Conde, J Lee, C Ay, H Martin, JJ Rosand, J Maguire, J AF Majersik, Jennifer J. Cole, John W. Golledge, Jonathan Rost, Natalia S. Chan, Yu-Feng Yvonne Gurol, M. Edip Lindgren, Arne G. Woo, Daniel Fernandez-Cadenas, Israel Chen, Donna T. Thijs, Vincent Worrall, Bradford B. Kamal, Ayeesha Bentley, Paul Wardlaw, Joanna M. Ruigrok, Ynte M. Battey, Thomas W. K. Schmidt, Reinhold Montaner, Joan Giese, Anne-Katrin Roquer, Jaume Jimenez-Conde, Jordi Lee, Chaeyoung Ay, Hakan Jose Martin, Juan Rosand, Jonathan Maguire, Jane CA Int Stroke Genetics Consortium TI Recommendations From the International Stroke Genetics Consortium, Part 1 Standardized Phenotypic Data Collection SO STROKE LA English DT Article DE cooperative behavior; genetics; genetics, population; outcome studies; phenotype risk factors; stroke ID HEALTH-CARE PROFESSIONALS; ISCHEMIC-STROKE; INTRACEREBRAL HEMORRHAGE; COMMON VARIANTS; DISEASE; SCORE; ASSOCIATION; CLASSIFICATION; DEFINITION; PREDICTION C1 [Majersik, Jennifer J.] Univ Utah, Dept Neurol, Salt Lake City, UT 84132 USA. [Cole, John W.] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. [Cole, John W.] Vet Affairs Med Ctr, Baltimore, MD USA. [Golledge, Jonathan] James Cook Univ, Queensland Res Ctr Peripheral Vasc Dis, Dept Vasc & Endovasc Surg, Townsville, Qld 4811, Australia. [Golledge, Jonathan] Townsville Hosp, Townsville, Qld, Australia. [Rost, Natalia S.; Gurol, M. Edip; Ay, Hakan; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Rost, Natalia S.; Gurol, M. Edip; Ay, Hakan; Rosand, Jonathan] Harvard Univ, Sch Med, Boston, MA USA. [Chan, Yu-Feng Yvonne] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Lindgren, Arne G.] Lund Univ, Dept Clin Sci, Lund, Sweden. [Lindgren, Arne G.] Skane Univ Hosp, Dept Neurol & Rehabil Med, Lund, Sweden. [Woo, Daniel] Univ Cincinnati, Dept Neurol, Cincinnati, OH 45221 USA. [Fernandez-Cadenas, Israel] Hosp Mutua Terrassa, Neurosci Dept, Fundacio Docencia & Recerca MutuaTerrassa, Barcelona, Spain. [Chen, Donna T.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA. [Worrall, Bradford B.] Univ Virginia, Dept Neurol, Charlottesville, VA USA. [Thijs, Vincent] KU Leuven Univ Leuven, Dept Neurosci, Leuven, Belgium. [Thijs, Vincent] Univ Hosp Leuven, Dept Neurol, Leuven, Belgium. [Thijs, Vincent] VIB Vesalius Res Ctr, B-3000 Louvain, Belgium. [Kamal, Ayeesha] Aga Khan Univ, Neurol Sect, Dept Med, Stroke Serv, Karachi, Pakistan. [Bentley, Paul] Univ London Imperial Coll Sci Technol & Med, Div Brain Sci, Charing Cross Hosp, London, England. [Wardlaw, Joanna M.] Western Gen Hosp, Div Neuroimaging Sci, Ctr Clin Brain Sci, Edinburgh EH4 2XU, Midlothian, Scotland. [Ruigrok, Ynte M.] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Neurol & Neurosurg, Utrecht, Netherlands. [Battey, Thomas W. K.; Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Boston, MA USA. [Schmidt, Reinhold] Med Univ Graz, Univ Clin Neurol, Clin Div Neurogeriatr, Graz, Austria. [Montaner, Joan] Univ Autonoma Barcelona, Vall dHebron Hosp, E-08193 Barcelona, Spain. [Montaner, Joan] Univ Autonoma Barcelona, Res Inst, Dept Neurol, E-08193 Barcelona, Spain. [Giese, Anne-Katrin] Univ Rostock, Albrecht Kossel Inst Neuroregenerat, D-18055 Rostock, Germany. [Roquer, Jaume; Jimenez-Conde, Jordi] DCEXS Univ Pompeu Fabra, Univ Autonoma Barcelona, Inst Hosp del Mar Invest Med, Dept Neurol, Barcelona, Spain. [Lee, Chaeyoung] Soongsil Univ, Dept Bioinformat & Life Sci, Seoul, South Korea. [Jose Martin, Juan] Natl Univ Cordoba, Sch Med, Dept Biochem & Mol Biol, Cordoba, Argentina. [Maguire, Jane] Univ Newcastle, Sch Nursing & Midwifery, Fac Hlth & Med, Callaghan, NSW 2308, Australia. RP Majersik, JJ (reprint author), Univ Utah, Dept Neurol, Stroke Ctr, 175 N Med Ctr Dr, Salt Lake City, UT 84132 USA. EM Jennifer.majersik@hsc.utah.edu RI Lee, Chaeyoung/C-7929-2012; Thijs, Vincent/C-3647-2009; JIMENEZ-CONDE, JORDI/C-1941-2012; IBIS, NEUROVASCULAR/O-1855-2015; Montaner, Joan/D-3063-2015 OI Lee, Chaeyoung/0000-0002-2940-1778; Thijs, Vincent/0000-0002-6614-8417; FU Medical Research Council [MR/J006971/1]; NINDS NIH HHS [NS69208, 1U10NS-86606-01, K23 NS083711, NS36695, NS69763, R01 NS082285, R01NS059727, U-01 NS069208, U10 NS086606, K23 NS064052] NR 38 TC 7 Z9 7 U1 3 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD JAN PY 2015 VL 46 IS 1 BP 279 EP + DI 10.1161/STROKEAHA.114.006839 PG 13 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AX1XB UT WOS:000346735800062 PM 25492903 ER PT J AU Battey, TWK Valant, V Kassis, SB Kourkoulis, C Lee, C Anderson, CD Falcone, GJ Jimenez-Conde, J Fernandez-Cadenas, I Pare, G Rundek, T James, ML Lemmens, R Lee, TH Tatlisumak, T Md, SJK Lindgren, A Mateen, FJ Berkowitz, AL Holliday, EG Majersik, J Maguire, J Sudlow, C Rosand, J AF Battey, Thomas W. K. Valant, Valerie Kassis, Sylvia Baedorf Kourkoulis, Christina Lee, Chaeyoung Anderson, Christopher D. Falcone, Guido J. Jimenez-Conde, Jordi Fernandez-Cadenas, Israel Pare, Guillaume Rundek, Tatjana James, Michael L. Lemmens, Robin Lee, Tsong-Hai Tatlisumak, Turgut Kittner, Steven J. Lindgren, Arne Mateen, Farrah J. Berkowitz, Aaron L. Holliday, Elizabeth G. Majersik, Jennifer Maguire, Jane Sudlow, Cathie Rosand, Jonathan CA Int Stroke Genetics Consortium TI Recommendations From the International Stroke Genetics Consortium, Part 2 Biological Sample Collection and Storage SO STROKE LA English DT Article DE biobank; biorepository; collaboration; consortium; genetics; risk factors ID GENOME-WIDE ASSOCIATION; ISCHEMIC-STROKE; METAANALYSIS; SCHIZOPHRENIA; SUBTYPES; BURDEN; LOCUS C1 [Battey, Thomas W. K.; Valant, Valerie; Kassis, Sylvia Baedorf; Kourkoulis, Christina; Anderson, Christopher D.; Falcone, Guido J.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Battey, Thomas W. K.; Kourkoulis, Christina; Anderson, Christopher D.; Falcone, Guido J.; Rosand, Jonathan] Massachusetts Gen Hosp, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. [Mateen, Farrah J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Battey, Thomas W. K.; Kourkoulis, Christina; Anderson, Christopher D.; Falcone, Guido J.; Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Lee, Chaeyoung] Soongsil Univ, Sch Syst Biomed Sci, Seoul, South Korea. [Jimenez-Conde, Jordi] Univ Autonoma Barcelona, Dept Neurol, Inst Hosp del Mar Invest Med, E-08193 Barcelona, Spain. [Fernandez-Cadenas, Israel] Hosp Mutua Terrassa, Fundacio Docencia & Recerca MutuaTerrassa, Terrassa, Spain. [Pare, Guillaume] McMaster Univ, Dept Clin Epidemiol & Biostat, Dept Pathol & Mol Med, Hamilton, ON, Canada. [Rundek, Tatjana] Univ Miami, Miller Sch Med, Coral Gables, FL 33124 USA. [James, Michael L.] Duke Univ, Dept Anesthesiol, Durham, NC 27706 USA. [James, Michael L.] Duke Univ, Dept Neurol, Durham, NC 27706 USA. [Lemmens, Robin] Univ Leuven, KU Leuven, Neurobiol Lab, Dept Neurosci,VIB Vesalius Res Ctr, Leuven, Belgium. [Lemmens, Robin] Univ Hosp Leuven, Dept Neurol, Leuven, Belgium. [Lee, Tsong-Hai] Linkou Chang Gung Mem Hosp, Dept Neurol, Taoyuan, Taiwan. [Tatlisumak, Turgut] Helsinki Univ Cent Hosp, Dept Neurol, Helsinki, Finland. [Kittner, Steven J.] Vet Adm Med Ctr, Dept Neurol, Baltimore, MD 21218 USA. [Kittner, Steven J.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Lindgren, Arne] Lund Univ, Dept Clin Sci, Lund, Sweden. [Lindgren, Arne] Skane Univ Hosp, Dept Neurol & Rehabil Med, Lund, Sweden. [Berkowitz, Aaron L.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Holliday, Elizabeth G.] Univ Newcastle, Sch Med & Publ Hlth, Newcastle, NSW 2300, Australia. [Holliday, Elizabeth G.; Maguire, Jane] Hunter Med Res Inst, Newcastle, NSW, Australia. [Majersik, Jennifer] Univ Utah, Div Vasc Neurol, Dept Neurol, Salt Lake City, UT USA. [Maguire, Jane] Univ Newcastle, Sch Nursing & Midwifery, Newcastle, NSW 2300, Australia. [Sudlow, Cathie] Univ Edinburgh, Div Clin Neurosci, Edinburgh, Midlothian, Scotland. [Sudlow, Cathie] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland. RP Rosand, J (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 6818, Boston, MA 02114 USA. EM jrosand@partners.org RI Lee, Chaeyoung/C-7929-2012; JIMENEZ-CONDE, JORDI/C-1941-2012; Falcone, Guido/L-2287-2016; OI Lee, Chaeyoung/0000-0002-2940-1778; Falcone, Guido/0000-0002-6407-0302; Anderson, Christopher/0000-0002-0053-2002 FU NINDS NIH HHS [U01NS069208, U01 NS069208, R01 NS059727] NR 17 TC 3 Z9 3 U1 4 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD JAN PY 2015 VL 46 IS 1 BP 285 EP + DI 10.1161/STROKEAHA.114.006851 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AX1XB UT WOS:000346735800063 PM 25492904 ER PT J AU Kolodny, E Fellgiebel, A Hilz, MJ Sims, K Caruso, P Phan, TG Politei, J Manara, R Burlina, A AF Kolodny, Edwin Fellgiebel, Andreas Hilz, Max J. Sims, Katherine Caruso, Paul Phan, Thanh G. Politei, Juan Manara, Renzo Burlina, Alessandro TI Cerebrovascular Involvement in Fabry Disease Current Status of Knowledge SO STROKE LA English DT Review DE basilar artery; Fabry disease; neuroimaging; pulvinar; risk factors; stroke; white matter ID ENZYME REPLACEMENT THERAPY; CEREBRAL-BLOOD-FLOW; YOUNG STROKE PATIENTS; FACTOR-V-LEIDEN; CRYPTOGENIC ISCHEMIC-STROKE; NERVOUS-SYSTEM INVOLVEMENT; WHITE-MATTER DISEASE; ALPHA-GALACTOSIDASE; CLINICAL-MANIFESTATIONS; X-CHROMOSOME C1 [Kolodny, Edwin] NYU, Dept Neurol, Sch Med, New York, NY 10003 USA. [Fellgiebel, Andreas] Univ Med Ctr Mainz, Dept Psychiat & Psychotherapy, Mainz, Germany. [Hilz, Max J.] Univ Erlangen Nurnberg, Dept Neurol, Erlangen, Germany. [Sims, Katherine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Sims, Katherine] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Caruso, Paul] Harvard Univ, Sch Med, Dept Radiol, Div Neuroradiol,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Phan, Thanh G.] Monash Univ, Stroke Unit, Monash Hlth & Stroke & Aging Res Grp, Dept Neurosci,Dept Med, Clayton, Vic 3800, Australia. [Politei, Juan] Fdn Estudio Enfermedades Neurometabol FESEN, Dept Neurol, Buenos Aires, DF, Argentina. [Manara, Renzo] Univ Salerno, Dept Neuroradiol, I-84100 Salerno, Italy. [Burlina, Alessandro] St Bassiano Hosp, Dept Internal Med, Neurol Unit, I-36061 Bassano Del Grappa, Italy. RP Burlina, A (reprint author), St Bassiano Hosp, Dept Internal Med, Neurol Unit, Via Lotti 40, I-36061 Bassano Del Grappa, Italy. EM alessandro.burlina@aslbassano.it OI Manara, Renzo/0000-0002-5130-3971 NR 133 TC 15 Z9 16 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD JAN PY 2015 VL 46 IS 1 BP 302 EP 313 DI 10.1161/STROKEAHA.114.006283 PG 12 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AX1XB UT WOS:000346735800066 PM 25492902 ER PT J AU Reiner, MF Martinod, K Stivala, S Savarese, G Camici, GG Luscher, TF Wagner, DD Beer, JH AF Reiner, Martin F. Martinod, Kimberly Stivala, Simona Savarese, Gianluigi Camici, Giovanni G. Luescher, Thomas F. Wagner, Denisa D. Beer, Juerg H. TI Dietary omega-3 alpha-linolenic acid does not prevent venous thrombosis in mice SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE Alpha-linolenic acid; cardiovascular disease; deep vein thrombosis; omega-3 fatty acids; venous thromboembolism ID DEEP-VEIN THROMBOSIS; POLYUNSATURATED FATTY-ACIDS; TISSUE FACTOR; CARDIOVASCULAR-DISEASE; ENDOTHELIAL-CELLS; FISH CONSUMPTION; METAANALYSIS; RISK; THROMBOEMBOLISM; ASSOCIATION AB Venous thromboembolism (VIE) is a leading cause of cardiovascular death. Omega-3 fatty acids (n-3 FA) exhibit protective effects against cardiovascular disease. Others and our group have reported that the plant-derived n-3 FA alpha-linolenic acid (ALA) displays antiinflammatory, anticoagulant and antiplatelet effects, thereby reducing atherosclerosis and arterial thrombosis in mice fed a high ALA diet. Since procoagulant factors such as tissue factor and fibrin as well as platelets and leukocytes are crucially involved in the development of VIE, we investigated possible protective effects of dietary ALA on venous thrombus formation in a mouse model of stenosis- and furthermore, in a mouse model of endothelial injury-induced venous thrombosis. Four week old C57BL/6 mice underwent four weeks of high (7.3g%) or low ALA (0.03g%) treatment before being exposed to inferior vena cava (IVC) stenosis for 48 hours or laser injury of the endothelium of the internal jugular vein (IJV). Thrombus generation frequency, thrombus size and composition (IVC stenosis group) and time to thrombus formation (endothelial injury group) were assessed. In addition, plasma glycocalicin, a marker of platelet activation, platelet P-selectin and activated integrin expression as well as plasma thrombin generation was determined, but did not reveal any significant differences between the groups. Despite its protective properties against arterial thrombus formation, dietary ALA did not protect against venous thrombosis neither in the IVC stenosis nor the endothelial injury model, further indicating that the biological processes involved in arterial and venous thrombosis are different. C1 [Reiner, Martin F.; Stivala, Simona; Savarese, Gianluigi; Camici, Giovanni G.; Luescher, Thomas F.; Beer, Juerg H.] Univ Zurich, Ctr Mol Cardiol, Lab Platelet Res, Schlieren, Switzerland. [Reiner, Martin F.; Stivala, Simona; Beer, Juerg H.] Cantonal Hosp Baden, Dept Internal Med, CH-5404 Baden, Switzerland. [Martinod, Kimberly; Wagner, Denisa D.] Harvard Univ, Childrens Hosp, Sch Med, Program Cellular & Mol Med, Boston, MA 02115 USA. [Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pediat, Div Hematol Oncol, Boston, MA 02115 USA. [Luescher, Thomas F.] Univ Zurich Hosp, Univ Heart Ctr, Dept Cardiol, Zurich, Switzerland. RP Beer, JH (reprint author), Cantonal Hosp Baden, Dept Med, Ergel 1, CH-5404 Baden, Switzerland. EM hansjuerg.beer@ksb.ch RI Savarese, Gianluigi/K-6845-2016; OI Savarese, Gianluigi/0000-0001-7732-0887; Martinod, Kimberly/0000-0002-1026-6107; Stivala, Simona/0000-0003-1549-8932 FU Swiss National Science Foundation [310030_144152/1] FX This study has been supported by the Swiss National Science Foundation (310030_144152/1). NR 28 TC 3 Z9 3 U1 0 U2 4 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JAN PY 2015 VL 113 IS 1 BP 177 EP 184 DI 10.1160/TH14-03-0200 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AY9KF UT WOS:000347868100017 PM 25231375 ER PT J AU Chang, JE Turley, SJ AF Chang, Jonathan E. Turley, Shannon J. TI Stromal infrastructure of the lymph node and coordination of immunity SO TRENDS IN IMMUNOLOGY LA English DT Review ID FIBROBLASTIC RETICULAR CELLS; HIGH ENDOTHELIAL VENULES; LECTIN RECEPTOR CLEC-2; SUBCAPSULAR SINUS MACROPHAGES; FOLLICULAR DENDRITIC CELLS; B-CELLS; CHEMOKINE RECEPTOR; T-CELLS; SPLENIC ARCHITECTURE; IN-VIVO AB The initiation of adaptive immune responses depends upon the careful maneuvering of lymphocytes and antigen into and within strategically placed lymph nodes (LNs). Non-hematopoietic stromal cells form the cellular infrastructure that directs this process. Once regarded as merely structural features of lymphoid tissues, these cells are now appreciated as essential regulators of immune cell trafficking, fluid flow, and LN homeostasis. Recent advances in the identification and in vivo targeting of specific stromal populations have resulted in striking new insights to the function of stromal cells and reveal a level of complexity previously unrealized. We discuss here recent discoveries that highlight the pivotal role that stromal cells play in orchestrating immune cell homeostasis and adaptive immunity. C1 [Chang, Jonathan E.] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Chang, Jonathan E.] Harvard Univ, Sch Med, Div Med Sci, Boston, MA 02115 USA. [Turley, Shannon J.] Genentech Inc, Dept Canc Immunol, San Francisco, CA 94080 USA. RP Turley, SJ (reprint author), Genentech Inc, Dept Canc Immunol, San Francisco, CA 94080 USA. EM turley.shannon@gene.com FU Cancer Research Institute (CRI) predoctoral training grant FX This work was funded by a Cancer Research Institute (CRI) predoctoral training grant. NR 111 TC 18 Z9 18 U1 3 U2 17 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 EI 1471-4981 J9 TRENDS IMMUNOL JI Trends Immunol. PD JAN PY 2015 VL 36 IS 1 BP 30 EP 39 DI 10.1016/j.it.2014.11.003 PG 10 WC Immunology SC Immunology GA AY9HU UT WOS:000347862100005 PM 25499856 ER PT J AU Collins, SP Storrow, AB Levy, PD Albert, N Butler, J Ezekowitz, JA Felker, GM Fermann, GJ Fonarow, GC Givertz, MM Hiestand, B Hollander, JE Lanfear, DE Pang, PS Peacock, WF Sawyer, DB Teerlink, JR Lenihan, DJ AF Collins, Sean P. Storrow, Alan B. Levy, Phillip D. Albert, Nancy Butler, Javed Ezekowitz, Justin A. Felker, G. Michael Fermann, Gregory J. Fonarow, Gregg C. Givertz, Michael M. Hiestand, Brian Hollander, Judd E. Lanfear, David E. Pang, Peter S. Peacock, W. Frank Sawyer, Douglas B. Teerlink, John R. Lenihan, Daniel J. TI Early Management of Patients With Acute Heart Failure: State of the Art and Future Directions-A Consensus Document from the SAEM/HFSA Acute Heart Failure Working Group SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID BRAIN NATRIURETIC PEPTIDE; RANDOMIZED CONTROLLED-TRIAL; IN-HOSPITAL MORTALITY; PULMONARY ARTERIAL-HYPERTENSION; EMERGENCY-DEPARTMENT PATIENTS; RIGHT-VENTRICULAR DYSFUNCTION; PRESERVED SYSTOLIC FUNCTION; NATIONAL REGISTRY ADHERE; END-DIASTOLIC PRESSURE; RISK STRATIFICATION AB Heart failure (HF) afflicts nearly 6 million Americans, resulting in 1million emergency department (ED) visits and over 1million annual hospital discharges. The majority of inpatient admissions originate in the ED; thus, it is crucial that emergency physicians and other providers involved in early management understand the latest developments in diagnostic testing, therapeutics, and alternatives to hospitalization. This article discusses contemporary ED management as well as the necessary next steps for ED-based acute HF research. C1 [Collins, Sean P.; Storrow, Alan B.; Sawyer, Douglas B.] Vanderbilt Univ, Nashville Vet Affairs Med Ctr, Dept Emergency Med, Nashville, TN 37235 USA. [Levy, Phillip D.] Wayne State Univ, Dept Emergency Med, Detroit, MI USA. [Fermann, Gregory J.] Univ Cincinnati, Dept Emergency Med, Cincinnati, OH USA. [Givertz, Michael M.] Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA USA. [Hiestand, Brian] Wake Forest Univ, Dept Emergency Med, Winston Salem, NC 27109 USA. [Hollander, Judd E.] Thomas Jefferson Univ, Dept Emergency Med, Philadelphia, PA 19107 USA. [Pang, Peter S.] Northwestern Univ, Dept Emergency Med, Chicago, IL 60611 USA. [Peacock, W. Frank] Baylor Univ, Dept Emergency Med, Houston, TX 77030 USA. [Albert, Nancy] Cleveland Clin, Div Cardiol, Cleveland, OH 44106 USA. [Butler, Javed] Emory Univ, Div Cardiol, Atlanta, GA 30322 USA. [Ezekowitz, Justin A.] Univ Alberta, Div Cardiol, Edmonton, AB, Canada. [Felker, G. Michael] Duke Univ, Div Cardiol, Durham, NC USA. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Div Cardiol, Los Angeles, CA USA. [Lanfear, David E.] Wayne State Univ, Div Cardiol, Detroit, MI USA. [Teerlink, John R.] Univ Calif San Francisco, Div Cardiol, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. [Lenihan, Daniel J.] Vanderbilt Univ, Div Cardiol, Nashville Vet Affairs Med Ctr, Nashville, TN 37232 USA. RP Collins, SP (reprint author), Vanderbilt Univ, Nashville Vet Affairs Med Ctr, Dept Emergency Med, 221 Kirkland Hall, Nashville, TN 37235 USA. EM sean.collins@vanderbilt.edu RI Ezekowitz, Justin/C-4579-2013; OI Ezekowitz, Justin/0000-0002-2724-4086; Hollander, Judd/0000-0002-1318-2785 FU NIH/NHLBI [K12HL1090]; Medtronic; Cardiorentis; Abbott Point-of-Care; Novartis; Medicines Company; Astellas; Intersection Medical; Radiometer; Abbott Diagnostics; Centers for Medicaid and Medicare Services (CMS); National Center for Advancing Translational Sciences [UL1TR000445]; Roche Diagnostics; National Institutes of Health; European Union; Health Resources Service Administration; NIH; Amgen; Trevena; Portola; Siemens; Mayday Foundation; Pfizer; NHLBI; Sanofi Aventis; Dyax; Insys; Novartis Pharmaceuticals; Cardiorentis Inc.; Trevena Inc.; Mespere; BG Medicine; NIH/NIMHD [5 R01 MD005849-04]; Alere; Abbott; Acorda Therapeutics Inc.; Cardio3 Bioscience; Cytokinetics; Sorbent Therapeutics; St. Jude FX SC-Research support from NIH/NHLBI, Medtronic, Cardiorentis, Abbott Point-of-Care, Novartis, The Medicines Company, Astellas, Intersection Medical, and Radiometer; consultant for Trevena, Novartis, Otsuka, Radiometer, The Medicines Company, Medtronic, BRAHMS, Insys, Intersection Medical, and Cardioxyl.; ABS-Current or recent grant support from Abbott Diagnostics, Centers for Medicaid and Medicare Services (CMS), NIH/NHLBI (K12HL1090), UL1TR000445 National Center for Advancing Translational Sciences, and Roche Diagnostics; current consultant for Roche Diagnostics, Novartis Pharmaceuticals Corp., Alere Diagnostics, Trevena, and Beckman Coulter.; JB-Research support from the National Institutes of Health, European Union, and Health Resources Service Administration; consultant for Amgen, Bayer, BG Medicine, Cardiocell, Celladon, Gambro, GE Healthcare, Medtronic, Novartis, Ono Pharma, Takeda, Trevena, and Zensun.; GMF-Consultant for Novartis, Amgen, Trevena, Roche Diagnostics, Singulex, Sorbent Therapeutics, and BMS; research funding from NIH, Novartis, Amgen, and Roche Diagnostics.; GJF-Research support from Novartis, Cardiorentis, Trevena, Portola, Radiometer, Medtronic, Siemens, Insys, The Mayday Foundation, and Pfizer; advisory board for Intersection Medical, Janssen, Insys, and The Medicines Company.; MMG-Scientific advisory board for Merck, Janssen, and Cardioxyl; grant support from NHLBI.; BH-Consulting relationship with Motive Medical Intelligence, Insight PD, and Intersection Medical Inc.; advisory board for Janssen Pharmaceuticals; research funding from The Medicines Company, Sanofi Aventis, Dyax, Radiometer, Cardiorentis, and Novartis.; PDL-Consultant for Novartis Pharmaceuticals, Trevena Inc., Intersection Medical, The Medicines Company, Ostuka, Janssen, Astellas, AstraZeneca, Beckman Coulter; research grant/support from Novartis Pharmaceuticals, Cardiorentis Inc., Trevena Inc., Intersection Medical, Mespere, and BG Medicine; support from NIH/NIMHD 5 R01 MD005849-04.; PSP-Consultant for Janssen, Medtronic, Novartis, Trevena, SpringLeafTx, BG Medicine, and Cornerstone Therapeutics; research support from Abbott, Alere, and NIH.; DBS-Grant support and consultant for Acorda Therapeutics Inc.; JT-Consulting fees/research grants from Amgen, Cardio3 Bioscience, Cytokinetics, Novartis, Sorbent Therapeutics, St. Jude, and Trevena. NR 162 TC 6 Z9 6 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD JAN PY 2015 VL 22 IS 1 BP 94 EP 112 DI 10.1111/acem.12538 PG 19 WC Emergency Medicine SC Emergency Medicine GA AY2WW UT WOS:000347447900013 PM 25423908 ER PT J AU Bromley, E Mikesell, L Armstrong, NP Young, AS AF Bromley, Elizabeth Mikesell, Lisa Armstrong, Nikki Panasci Young, Alexander S. TI "You Might Lose Him Through the Cracks": Clinicians' Views on Discharge from Assertive Community Treatment SO ADMINISTRATION AND POLICY IN MENTAL HEALTH AND MENTAL HEALTH SERVICES RESEARCH LA English DT Article DE Assertive Community Treatment; Serious mental illness; Community mental health; Therapeutic alliance ID INTENSIVE CASE-MANAGEMENT; MENTAL-HEALTH-SERVICES; TREATMENT TEAMS; CRITICAL INGREDIENTS; TREATMENT PROGRAM; RANDOMIZED-TRIAL; ACT; ADHERENCE; RECOVERY; ILLNESS AB Assertive Community Treatment (ACT) teams are increasingly interested in improving access to ACT through discharge of improved clients to less intensive mental health care services. We report results from a process evaluation of three teams in the VA's ACT program, Mental Health Intensive Case Management (MHICM), that began to implement discharge. MHICM clinicians (n = 15) describe significant barriers to discharge. Clinicians support the concept of discharge but raise concerns about clients' future stability, clients' feelings about discharge, and other aspects of the discharge process. We propose strategies that can be used to support clinicians and clients in discharge decision-making. C1 [Bromley, Elizabeth; Young, Alexander S.] Greater Los Angeles Dept Vet Affairs Healthcare C, Desert Pacific VA Mental Illness Res,Educ & Clin, Los Angeles, CA USA. [Bromley, Elizabeth; Young, Alexander S.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, Ctr Hlth Serv & Soc, Los Angeles, CA 90024 USA. [Bromley, Elizabeth] UCLA Ctr Hlth Serv & Soc, West Los Angeles VA Healthcare Ctr, Los Angeles, CA 90024 USA. [Mikesell, Lisa] Rutgers State Univ, Sch Commun & Informat, New Brunswick, NJ 08903 USA. [Armstrong, Nikki Panasci] San Francisco VA Med Ctr, San Francisco, CA USA. RP Bromley, E (reprint author), UCLA Ctr Hlth Serv & Soc, West Los Angeles VA Healthcare Ctr, 10920 Wilshire Blvd,Suite 300, Los Angeles, CA 90024 USA. EM ebromley@mednet.ucla.edu; mikesell.lisa@gmail.com; nikki@hawaii.edu; ayoung@mednet.ucla.edu NR 46 TC 0 Z9 0 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-587X EI 1573-3289 J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD JAN PY 2015 VL 42 IS 1 BP 99 EP 110 DI 10.1007/s10488-014-0547-3 PG 12 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AY2EK UT WOS:000347401200011 PM 24692027 ER PT J AU Rasmussen, DD Kincaid, CL AF Rasmussen, Dennis D. Kincaid, Carrie L. TI Acoustic Startle in Alcohol-Na < ve Male Rats Predicts Subsequent Voluntary Alcohol Intake and Alcohol Preference SO ALCOHOL AND ALCOHOLISM LA English DT Article ID FEAR-POTENTIATED STARTLE; PREFERRING P RATS; ANXIETY DISORDERS; RECEPTOR ANTAGONIST; WISTAR RATS; ETHANOL; MODULATION; DRINKING; CONSUMPTION; WITHDRAWAL AB Aims: Acoustic startle response in rats is used to model sensorimotor reactivity. The aim of the study was to determine whether acoustic startle response in alcohol-na < ve rats predicts subsequent increased voluntary alcohol drinking or alcohol preference. Methods: Startle responses to 90, 95 and 100 decibel (dB) white noise stimuli presented in counterbalanced semi-randomized order were tested in alcohol-na < ve young adult male Wistar rats before voluntary alcohol intake was established with an intermittent alcohol access (IAA) model. Results: Startle amplitude in response to 95 or 100 dB stimuli was positively correlated with subsequent alcohol intake and alcohol preference following 3 months of IAA. Rats with high (median split) pre-IAA startle amplitude in response to 95 or 100 dB stimuli developed increased alcohol intake as well as increased alcohol preference following 3 months of IAA, relative to rats with low pre-IAA startle amplitude. Conclusion: Startle response to moderate acoustic stimuli can be a predictive index of vulnerability to developing increased alcohol drinking. C1 VA Puget Sound Hlth Care Syst, VISN Mental Illness Res Educ & Clin Ctr 20, Seattle, WA 98195 USA. Univ Washington, Seattle, WA 98195 USA. RP Rasmussen, DD (reprint author), VA Med Ctr, 116 MIRECC,1660 S Columbian Way, Seattle, WA 98108 USA. EM drasmuss@u.washington.edu FU US Army Medical Research Acquisition Activity CDMRP [W81XWH-13-1-0126]; National Institutes of Health [AA10567] FX This work was supported in part by resources from the VA Puget Sound Health Care System, Seattle, Washington; US Army Medical Research Acquisition Activity CDMRP (contract number W81XWH-13-1-0126); and National Institutes of Health (grant number AA10567). NR 32 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0735-0414 EI 1464-3502 J9 ALCOHOL ALCOHOLISM JI Alcohol Alcohol. PD JAN-FEB PY 2015 VL 50 IS 1 BP 56 EP 61 DI 10.1093/alcalc/agu065 PG 6 WC Substance Abuse SC Substance Abuse GA AY2JL UT WOS:000347415400009 PM 25305255 ER PT J AU Kumar, PS Medina-Lezama, J Morey-Vargas, O Zamani, P Bolanos-Salazar, JF Chirinos, DA Haines, P Khan, ZA Coacalla-Guerra, JC Davalos-Robles, ME Llerena-Dongo, GR Zapata-Ponze, M Chirinos, JA AF Kumar, Prithvi Shiva Medina-Lezama, Josefina Morey-Vargas, Oscar Zamani, Payman Bolanos-Salazar, Juan F. Chirinos, Diana A. Haines, Philip Khan, Zubair A. Coacalla-Guerra, Johanna C. Davalos-Robles, Maria E. Llerena-Dongo, Gladys R. Zapata-Ponze, Mardelangel Chirinos, Julio A. CA PREVENCION Investigators TI Prospective Risk Factors for Increased Central Augmentation Index in Men and Women SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE augmentation index; blood pressure; hypertension; prospective; gender differences; wave reflections ID ARTERIAL WAVE REFLECTIONS; PERUVIAN ANDEAN HISPANICS; CENTRAL PULSE PRESSURE; CARDIOVASCULAR RISK; LONGITUDINAL OBSERVATIONS; ENDOTHELIAL FUNCTION; METABOLIC SYNDROME; AORTIC IMPEDANCE; REFERENCE VALUES; AGE DEPENDENCY AB BACKGROUND Arterial wave reflections are important determinants of central pressure pulsatility and left ventricular afterload. The augmentation index (AIx) is the most widely used surrogate of arterial wave reflections. Despite multiple cross-sectional studies assessing the correlates of AIx, little prospective data exist regarding changes in AIx over time. We aimed to assess the predictors of changes in AIx over time in adults from the general population. METHODS We performed radial arterial tonometry assessments a median of 3.18 +/- 0.4 years apart on 143 nondiabetic adult participants in the population-based PREVENCION study. Central AIx was obtained using the generalized transfer function of the Sphygmocor device. RESULTS Predictors of the change in AIx over time were investigated. Among men (n = 67), the change in AIx was predicted by abdominal obesity (standardized beta for waist circumference = 0.34; P = 0.002), impaired fasting glucose (standardized beta = 0.24; P = 0.009), and the change in heart rate (standardized beta = -0.78; P < 0.001). Among women (n = 76), the change in AIx was predicted by non-high-density lipoprotein cholesterol (standardized beta = 0.33; P = 0.001), C-reactive protein levels (standardized beta = 0.24; P = 0.02), change in mean arterial pressure (standardized beta = 0.33; P = 0.001), and change in heart rate (standardized beta = -0.52; P < 0.001). CONCLUSIONS Metabolic and inflammatory factors predicted changes in AIx over time, with important sex differences. Metabolic factors, such as abdominal obesity and impaired fasting glucose, predicted changes in AIx in men, whereas C-reactive protein and non-high-density lipoprotein cholesterol levels predicted changes in women. Our findings highlight the impact of sex on arterial properties and may guide the design of interventions to favorably impact changes in late systolic pressure augmentation. C1 [Kumar, Prithvi Shiva; Zamani, Payman; Bolanos-Salazar, Juan F.; Haines, Philip; Khan, Zubair A.; Chirinos, Julio A.] Philadelphia VA Med Ctr, Div Cardiol, Philadelphia, PA 19104 USA. [Kumar, Prithvi Shiva; Zamani, Payman; Bolanos-Salazar, Juan F.; Haines, Philip; Khan, Zubair A.; Chirinos, Julio A.] Univ Penn, Philadelphia, PA 19104 USA. [Medina-Lezama, Josefina; Coacalla-Guerra, Johanna C.; Davalos-Robles, Maria E.; Llerena-Dongo, Gladys R.; Zapata-Ponze, Mardelangel] Santa Maria Catholic Univ, Dept Med, Arequipa, Peru. [Morey-Vargas, Oscar] Mayo Clin, Dept Med, Rochester, MN USA. [Chirinos, Diana A.] Univ Miami, Dept Psychol, Miami, FL USA. RP Kumar, PS (reprint author), Philadelphia VA Med Ctr, Div Cardiol, Philadelphia, PA 19104 USA. EM prithvisk@gmail.com OI Khan, Zubair/0000-0002-0451-9155 FU FOCUS Junior Faculty Investigator Award; Edna G. Kynett Memorial Foundation; Santa Maria Research Institute (Arequipa, Peru); [5-T32-HL007843-17]; [UL1RR024134] FX This work was supported through a FOCUS Junior Faculty Investigator Award for Research in Women's Cardiovascular Health supported by the Edna G. Kynett Memorial Foundation and the Santa Maria Research Institute (Arequipa, Peru). Payman Zamani received research and salary support from 5-T32-HL007843-17 and UL1RR024134. The abstract of this work was presented at the American College of Cardiology Scientific Annual Meeting 2013. NR 37 TC 2 Z9 2 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0895-7061 EI 1941-7225 J9 AM J HYPERTENS JI Am. J. Hypertens. PD JAN PY 2015 VL 28 IS 1 BP 121 EP 126 DI 10.1093/ajh/hpu093 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AY2JI UT WOS:000347415100016 ER PT J AU Mortensen, LJ Alt, C Turcotte, R Masek, M Liu, TM Cote, DC Xu, C Intini, G Lin, CP AF Mortensen, Luke J. Alt, Clemens Turcotte, Raphael Masek, Marissa Liu, Tzu-Ming Cote, Daniel C. Xu, Chris Intini, Giuseppe Lin, Charles P. TI Femtosecond laser bone ablation with a high repetition rate fiber laser source SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID STEM-CELLS; MICROSCOPY; PULSES; OSTEOTOMY; DAMAGE; TISSUES; REGENERATION; FLUORESCENCE; DIELECTRICS; BREAKDOWN AB Femtosecond laser pulses can be used to perform very precise cutting of material, including biological samples from subcellular organelles to large areas of bone, through plasma-mediated ablation. The use of a kilohertz regenerative amplifier is usually needed to obtain the pulse energy required for ablation. This work investigates a 5 megahertz compact fiber laser for near-video rate imaging and ablation in bone. After optimization of ablation efficiency and reduction in autofluorescence, the system is demonstrated for the in vivo study of bone regeneration. Image-guided creation of a bone defect and longitudinal evaluation of cellular injury response in the defect provides insight into the bone regeneration process. (C) 2014 Optical Society of America C1 [Mortensen, Luke J.; Intini, Giuseppe] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Mortensen, Luke J.; Alt, Clemens; Turcotte, Raphael; Masek, Marissa; Liu, Tzu-Ming; Lin, Charles P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Adv Microscopy Program,Ctr Syst Biol, Boston, MA USA. [Mortensen, Luke J.; Alt, Clemens; Turcotte, Raphael; Masek, Marissa; Liu, Tzu-Ming; Lin, Charles P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [Turcotte, Raphael] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Liu, Tzu-Ming] Natl Taiwan Univ, Inst Biomed Engn, Taipei 10764, Taiwan. [Cote, Daniel C.] Univ Laval, Ctr Rech Univ Laval Robert Giffard, Quebec City, PQ G1J 2G3, Canada. [Xu, Chris] Cornell Univ, Sch Appl & Engn Phys, Ithaca, NY USA. [Intini, Giuseppe; Lin, Charles P.] Harvard Stem Cell Inst, Cambridge, MA USA. RP Mortensen, LJ (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, 188 Longwood Ave, Boston, MA 02115 USA. EM Giuseppe_Intini@hsdm.harvard.edu; Charles_Lin@hms.harvard.edu RI Liu, Tzu-Ming/M-9331-2016; OI Mortensen, Luke/0000-0002-4331-4099 FU National Institutes of Health [NIH EB017274]; NIH/NIDCR [DE021069] FX This work was supported by grants from the National Institutes of Health- NIH EB017274 to C. P. Lin and NIH/NIDCR DE021069 to G. Intini. NR 50 TC 4 Z9 5 U1 4 U2 26 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD JAN 1 PY 2015 VL 6 IS 1 BP 32 EP 42 DI 10.1364/BOE.6.000032 PG 11 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA AY3HJ UT WOS:000347474800004 PM 25657872 ER PT J AU Wei, YY Tenzen, T Ji, HK AF Wei, Yingying Tenzen, Toyoaki Ji, Hongkai TI Joint analysis of differential gene expression in multiple studies using correlation motifs SO BIOSTATISTICS LA English DT Article DE Bayes hierarchical model; Correlation motif; EM algorithm; Microarray; Multiple datasets ID HEDGEHOG; TARGETS; PATHWAY; MODEL AB The standard methods for detecting differential gene expression are mostly designed for analyzing a single gene expression experiment. When data from multiple related gene expression studies are available, separately analyzing each study is not ideal as it may fail to detect important genes with consistent but relatively weak differential signals in multiple studies. Jointly modeling all data allows one to borrow information across studies to improve the analysis. However, a simple concordance model, in which each gene is assumed to be differential in either all studies or none of the studies, is incapable of handling genes with study-specific differential expression. In contrast, a model that naively enumerates and analyzes all possible differential patterns across studies can deal with study-specificity and allow information pooling, but the complexity of its parameter space grows exponentially as the number of studies increases. Here, we propose a correlation motif approach to address this dilemma. This approach searches for a small number of latent probability vectors called correlation motifs to capture the major correlation patterns among multiple studies. The motifs provide the basis for sharing information among studies and genes. The approach has flexibility to handle all possible study-specific differential patterns. It improves detection of differential expression and overcomes the barrier of exponential model complexity. C1 [Wei, Yingying; Ji, Hongkai] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Wei, Yingying] Chinese Univ Hong Kong, Dept Stat, Shatin, Hong Kong, Peoples R China. [Tenzen, Toyoaki] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Ctr Regenerat Med, Boston, MA 02114 USA. RP Ji, HK (reprint author), Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. EM hji@jhu.edu FU National Institutes of Health [R01HG006282]; National Institutes of Health grant [R01HG006282] FX The research is supported by the National Institutes of Health grant R01HG006282. Funding to pay the Open Access publication charges for this article was provided by the National Institutes of Health grant R01HG006282. NR 18 TC 5 Z9 5 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 EI 1468-4357 J9 BIOSTATISTICS JI Biostatistics PD JAN PY 2015 VL 16 IS 1 BP 31 EP 46 DI 10.1093/biostatistics/kxu038 PG 16 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA AY2JZ UT WOS:000347417500005 PM 25143368 ER PT J AU Kohno, M Ghahremani, DG Morales, AM Robertson, CL Ishibashi, K Morgan, AT Mandelkern, MA London, ED AF Kohno, Milky Ghahremani, Dara G. Morales, Angelica M. Robertson, Chelsea L. Ishibashi, Kenji Morgan, Andrew T. Mandelkern, Mark A. London, Edythe D. TI Risk-Taking Behavior: Dopamine D2/D3 Receptors, Feedback, and Frontolimbic Activity SO CEREBRAL CORTEX LA English DT Article DE decision-making; dopamine receptors; fMRI; pet; risk-taking; striatum ID NUCLEUS-ACCUMBENS DOPAMINE; EXCITATORY AMINO-ACIDS; REFERENCE TISSUE MODEL; DECISION-MAKING; PREFRONTAL CORTEX; SUBCORTICAL CIRCUITS; COGNITIVE CONTROL; WORKING-MEMORY; FRONTAL-CORTEX; HUMAN BRAIN AB Decision-making involves frontolimbic and dopaminergic brain regions, but how prior choice outcomes, dopamine neurotransmission, and frontostriatal activity are integrated to affect choices is unclear. We tested 60 healthy volunteers using the Balloon Analogue Risk Task (BART) during functional magnetic resonance imaging. In the BART, participants can pump virtual balloons to increase potential monetary reward or cash out to receive accumulated reward; each pump presents greater risk and potential reward (represented by the pump number). In a separate session, we measured striatal D2/D3 dopamine receptor binding potential (BPND) with positron emission tomography in 13 of the participants. Losses were followed by fewer risky choices than wins; and during risk-taking after loss, amygdala and hippocampal activation exhibited greater modulation by pump number than after a cash-out event. Striatal D2/D3 BPND was positively related to the modulation of ventral striatal activation when participants decided to cash out and negatively to the number of pumps in the subsequent trial; but negatively related to the modulation of prefrontal cortical activation by pump number when participants took risk, and to overall earnings. These findings provide in vivo evidence for a potential mechanism by which dopaminergic neurotransmission may modulate risk-taking behavior through an interactive system of frontal and striatal activity. C1 [Kohno, Milky; Ghahremani, Dara G.; Morales, Angelica M.; Ishibashi, Kenji; Morgan, Andrew T.; London, Edythe D.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Kohno, Milky; Morales, Angelica M.; London, Edythe D.] Univ Calif Los Angeles, Neurosci Interdept Program, Los Angeles, CA 90024 USA. [Robertson, Chelsea L.; London, Edythe D.] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90024 USA. [London, Edythe D.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. [London, Edythe D.] Univ Calif Los Angeles, Semel Inst, Los Angeles, CA 90024 USA. [Robertson, Chelsea L.; Ishibashi, Kenji; Morgan, Andrew T.; Mandelkern, Mark A.; London, Edythe D.] Univ Calif Irvine, Vet Adm Greater Los Angeles Healthcare Syst, Irvine, CA USA. [Mandelkern, Mark A.] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. RP London, ED (reprint author), Univ Calif Los Angeles, Semel Inst, 740 Westwood Plaza,C8-831, Los Angeles, CA 90024 USA. EM elondon@mednet.ucla.edu RI Morales, Angelica/P-4108-2015; OI Morgan, Andrew/0000-0001-6017-2179 FU NIH [P20 DA022539, R01 DA020726, F31 DA033120-02, F31 DA0331-17]; Philip Morris USA; [T32 DA 024635] FX The research described here was funded in part by NIH grants P20 DA022539 and R01 DA020726, a grant from Philip Morris USA, and endowments from the Thomas P. and Katherine K. Pike Chair in Addiction Studies, and the Marjorie M. Greene Trust. M. K., A. M. M., and C.L.R. were supported by training grant T32 DA 024635. M. K. and A. M. M. were also supported by NIH grants F31 DA033120-02 and F31 DA0331-17, respectively. None of the sponsors were involved with the design, collection, analysis or interpretation of data, writing the manuscript, or the decision to submit the manuscript for publications. NR 63 TC 21 Z9 21 U1 3 U2 13 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD JAN PY 2015 VL 25 IS 1 BP 236 EP 245 DI 10.1093/cercor/bht218 PG 10 WC Neurosciences SC Neurosciences & Neurology GA AY2KA UT WOS:000347417600022 PM 23966584 ER PT J AU Cardinal-Fernandez, P Esteban, A Thompson, BT Lorente, JA AF Cardinal-Fernandez, Pablo Esteban, Andres Thompson, B. Taylor Lorente, Jose A. TI ARDS Lessons Learned From the Heart SO CHEST LA English DT Editorial Material ID RESPIRATORY-DISTRESS-SYNDROME; DIFFUSE ALVEOLAR DAMAGE; BERLIN DEFINITION; INTERSTITIAL PNEUMONIA; AUTOPSY C1 [Cardinal-Fernandez, Pablo; Esteban, Andres] Hosp Univ Getafe, Serv Med Intens, Madrid 28905, Spain. [Cardinal-Fernandez, Pablo; Esteban, Andres; Lorente, Jose A.] CIBER Enfermedades Resp, Madrid, Spain. [Thompson, B. Taylor] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Lorente, Jose A.] Univ Europea, Madrid, Spain. RP Lorente, JA (reprint author), Hosp Univ Getafe, Serv Med Intens, Madrid 28905, Spain. EM joseangel.lorente@salud.madrid.org NR 14 TC 6 Z9 6 U1 0 U2 3 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 2015 VL 147 IS 1 BP 7 EP 8 DI 10.1378/chest.14-0874 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AY3AH UT WOS:000347456500013 PM 25560852 ER PT J AU Tapias, LF Mercier, O Ghigna, MR Lahon, B Lee, H Mathisen, DJ Dartevelle, P Lanuti, M AF Tapias, Luis F. Mercier, Olaf Ghigna, Maria R. Lahon, Benoit Lee, Hang Mathisen, Douglas J. Dartevelle, Philippe Lanuti, Michael TI Validation of a Scoring System to Predict Recurrence of Resected Solitary Fibrous Tumors of the Pleura SO CHEST LA English DT Article AB BACKGROUND: Solitary fibrous tumors of the pleura (SFTPs) are infrequent neoplasms with no standardized criteria to predict risk of recurrence after curative surgery. The aim of the present study is to validate a recently proposed recurrence score in a large European cohort of patients with SFTP. METHODS: Validation of a previously published scoring system was assessed in a population of 113 patients who underwent complete resection of SFTPs. Patients were scored according to the pleural origin, morphology, size, hypercellularity, presence of necrosis or hemorrhage, and number of mitoses in their SFTPs. Receiver operating characteristic curves were plotted for the score. Time to recurrence analysis was performed using the Kaplan-Meier and Cox proportional hazards methods. RESULTS: After a mean follow-up of 13.2 perpendicular to 7.3 years, there were nine recurrences (8.0%). Score performance to predict recurrence was as follows: sensitivity -78%, specificity -74%, positive likelihood ratio -3.0, and negative likelihood ratio -0.3. A cutoff of 3 points was used to classify 79 patients (69.9%) at low risk and 34 patients (30.1%) at high risk for recurrence. A high-risk classification was significantly associated with more recurrences during follow-up (P = .004), worse overall survival (P = .0008), more extensive lung resections (P = .001), and the use of adjuvant therapies (P = .009). The present score outperformed England's criteria (P = .049) and de Perrot classification (P < .001) when predicting SFTP recurrence. CONCLUSIONS: The proposed scoring system, which combines common clinical and histologic features of resected SFTPs, remains predictive of recurrence in a separate patient population. The simple score may guide the postoperative surveillance of this uncommon tumor. C1 [Tapias, Luis F.; Mathisen, Douglas J.; Lanuti, Michael] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Mercier, Olaf; Ghigna, Maria R.; Lahon, Benoit; Dartevelle, Philippe] Marie Lannelongue Hosp, Dept Thorac & Vasc Surg & Heart Lung Transplantat, Paris, France. RP Lanuti, M (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM mlanuti@mgh.harvard.edu FU Harvard Catalyst: The Harvard Clinical and Translational Science Center; National Center for Research Resources; National Center for Advancing Translational Sciences, National Institutes of Health [8UL1TR000170-05]; Harvard University; academic health-care centers FX The statistical analysis of this work was conducted with support from Harvard Catalyst: The Harvard Clinical and Translational Science Center, National Center for Research Resources, and the National Center for Advancing Translational Sciences, National Institutes of Health [Award 8UL1TR000170-05], and financial contributions from Harvard University and its affiliated academic health-care centers NR 10 TC 9 Z9 11 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 2015 VL 147 IS 1 BP 216 EP 223 DI 10.1378/chest.14-1180 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AY3AH UT WOS:000347456500041 PM 25103552 ER PT J AU Dewan, NA Nieto, FJ Somers, VK AF Dewan, Naresh A. Nieto, F. Javier Somers, Virend K. TI Intermittent Hypoxemia and OSA Implications for Comorbidities SO CHEST LA English DT Editorial Material ID OBSTRUCTIVE SLEEP-APNEA; POSITIVE AIRWAY PRESSURE; SYMPATHETIC-NERVE RESPONSES; HYPOXIA-INDUCIBLE FACTORS; LONG-TERM EFFICACY; BLOOD-PRESSURE; MOUSE MODEL; NEUROCOGNITIVE FUNCTION; CARDIOVASCULAR-DISEASE; ATRIAL-FIBRILLATION AB OSA is a common chronic disorder that is associated with significant morbidity and mortality including cardiovascular, metabolic, and neurocognitive disease and increased cancer-related deaths. OSA is characterized by recurrent episodes of apneas and hypopneas associated with repetitive episodes of intermittent hypoxemia, intrathoracic pressure changes, and arousals. Intermittent hypoxemia (IH) is now being recognized as a potential major factor contributing to the pathogenesis of OSA-related comorbidities. OSA-related high-frequency IH is characterized by cycles of hypoxemia with reoxygenation that is distinctly different than sustained low-frequency hypoxia and contributes to ischemia-reperfusion injury. Data from both animal and human studies support mechanistic links between IH and its adverse impact at the tissue level. IH promotes oxidative stress by increased production of reactive oxygen species and angiogenesis, increased sympathetic activation with BP elevation, and systemic and vascular inflammation with endothelial dysfunction that contributes to diverse multiorgan chronic morbidity and mortality affecting cardiovascular disease, metabolic dysfunction, cognitive decline, and progression of cancer. Data from observational studies in large population groups also support the role for hypoxia in the pathogenesis of OSA comorbidity. Treatment with CPAP to reverse OSA-related symptoms and comorbidities has been shown to provide variable benefit in some but not all patient groups. Early treatment with CPAP makes intuitive sense to promote maximal functional recovery and minimize residual injury. More studies are needed to determine the interacting effects of IH and obesity, differential effects of both short-term and long-term hypoxemia, and the effect of CPAP treatment. C1 [Dewan, Naresh A.] Creighton Univ, Dept Med, Div Pulm Crit Care & Sleep Med, Omaha, NE 68178 USA. US Dept Vet Affairs, Omaha VA Med Ctr, Pulm Sect, Omaha, NE USA. Univ Wisconsin, Sch Med & Publ Hlth, Board Regents Univ Wisconsin Syst, Madison, WI USA. Mayo Clin, Mayo Fdn Med Educ & Res, Coll Med, Sleep & Cardiovasc Clin Res Unit, Rochester, MN USA. RP Dewan, NA (reprint author), Creighton Univ, Dept Med, Div Pulm Crit Care & Sleep Med, Omaha, NE 68178 USA. FU National Institutes of Health (NIH) [R01HL062252-11]; University of Wisconsin; NIH [HL-65176] FX Dr Nieto's contributions were supported in part by the National Institutes of Health (NIH) [Grant R01HL062252-11] and by the University of Wisconsin Helfaer Endowed Chair of Public Health. Dr Somers' contribution to this work was supported by the NIH [Grant HL-65176]. NR 86 TC 45 Z9 52 U1 3 U2 28 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 2015 VL 147 IS 1 BP 266 EP 274 DI 10.1378/chest.14-0500 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AY3AH UT WOS:000347456500047 PM 25560865 ER PT J AU Anderson, KC Potash, J AF Anderson, Kenneth C. Potash, Jesse TI Clinical Cancer Research: The 20th Anniversary SO CLINICAL CANCER RESEARCH LA English DT Editorial Material C1 [Anderson, Kenneth C.; Potash, Jesse] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2015 VL 21 IS 1 BP 3 EP 3 DI 10.1158/1078-0432.CCR-14-2455 PG 1 WC Oncology SC Oncology GA AY3CQ UT WOS:000347462600001 PM 25564568 ER PT J AU Di Cosimo, S Sathyanarayanan, S Bendell, JC Cervantes, A Stein, MN Brana, I Roda, D Haines, BB Zhang, T Winter, CG Jha, S Xu, YY Frazier, J Klinghoffer, RA Leighton-Swayze, A Song, Y Ebbinghaus, S Baselga, J AF Di Cosimo, Serena Sathyanarayanan, Sriram Bendell, Johanna C. Cervantes, Andres Stein, Mark N. Brana, Irene Roda, Desamparados Haines, Brian B. Zhang, Theresa Winter, Christopher G. Jha, Sharda Xu, Youyuan Frazier, Jason Klinghoffer, Richard A. Leighton-Swayze, Ann Song, Yang Ebbinghaus, Scot Baselga, Jose TI Combination of the mTOR Inhibitor Ridaforolimus and the Anti-IGF1R Monoclonal Antibody Dalotuzumab: Preclinical Characterization and Phase I Clinical Trial SO CLINICAL CANCER RESEARCH LA English DT Article ID ADVANCED SOLID TUMORS; BREAST-CANCER; RECEPTOR PATHWAY; EVEROLIMUS; RESISTANCE; PROGNOSIS; PI3K; DEPENDENCE; TAMOXIFEN; 3-KINASE AB Purpose: Mammalian target of rapamycin (mTOR) inhibition activates compensatory insulin-like growth factor receptor (IGFR) signaling. We evaluated the ridaforolimus (mTOR inhibitor) and dalotuzumab (anti-IGF1R antibody) combination. Experimental Design: In vitro and in vivo models, and a phase I study in which patients with advanced cancer received ridaforolimus (10-40 mg/day every day x 5/week) and dalotuzumab (10 mg/kg/week or 7.5 mg/kg/every other week) were explored. Results: Preclinical studies demonstrated enhanced pathway inhibition with ridaforolimus and dalotuzumab. With 87 patients treated in the phase I study, main dose-limiting toxicities (DLT) of the combination were primarily mTOR-related stomatitis and asthenia at doses of ridaforolimus lower than expected, suggesting blockade of compensatory pathways in normal tissues. Six confirmed partial responses were reported (3 patients with breast cancer); 10 of 23 patients with breast cancer and 6 of 11 patients with ER+/high-proliferative breast cancer showed antitumor activity. Conclusions: Our study provides proof-of-concept that inhibiting the IGF1R compensatory response to mTOR inhibition is feasible with promising clinical activity in heavily pretreated advanced cancer, particularly in ER+/high-proliferative breast cancer. (C) 2014 AACR. C1 [Di Cosimo, Serena; Brana, Irene] Vall dHebron Univ Hosp, Barcelona, Spain. [Sathyanarayanan, Sriram; Haines, Brian B.; Zhang, Theresa; Winter, Christopher G.; Jha, Sharda; Xu, Youyuan; Frazier, Jason; Klinghoffer, Richard A.; Leighton-Swayze, Ann; Song, Yang; Ebbinghaus, Scot] Merck & Co Inc, Whitehouse Stn, NJ USA. [Bendell, Johanna C.] Sarah Cannon Res Inst, Nashville, TN USA. [Cervantes, Andres; Roda, Desamparados] Univ Valencia, Inst Hlth Res INCLIVA, Valencia, Spain. [Stein, Mark N.] Canc Inst New Jersey, Brunswick, ME USA. [Baselga, Jose] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Baselga, J (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave,Suite M2001, New York, NY 10065 USA. EM baselgaj@mskcc.org RI Serena, Di Cosimo/E-9418-2017 OI Serena, Di Cosimo/0000-0002-4666-8052 FU Merck & Co., Inc., Whitehouse Station, NJ, USA FX This study was funded by Merck & Co., Inc., Whitehouse Station, NJ, USA. NR 32 TC 18 Z9 18 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2015 VL 21 IS 1 BP 49 EP 59 DI 10.1158/1078-0432.CCR-14-0940 PG 11 WC Oncology SC Oncology GA AY3CQ UT WOS:000347462600009 PM 25320355 ER PT J AU Messersmith, WA Shapiro, GI Cleary, JM Jimeno, A Dasari, A Huang, B Shaik, MN Cesari, R Zheng, XX Reynolds, JM English, PA McLachlan, KR Kern, KA LoRusso, PM AF Messersmith, Wells A. Shapiro, Geoffrey I. Cleary, James M. Jimeno, Antonio Dasari, Arvind Huang, Bo Shaik, M. Naveed Cesari, Rossano Zheng, Xianxian Reynolds, Jennifer M. English, Patricia A. McLachlan, Karen R. Kern, Kenneth A. LoRusso, Patricia M. TI A Phase I, Dose-Finding Study in Patients with Advanced Solid Malignancies of the Oral gamma-Secretase Inhibitor PF-03084014 SO CLINICAL CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; NOTCH SIGNALING PATHWAY; BREAST-CANCER MODELS; TARGETING NOTCH; DESMOID TUMORS; STEM-CELLS; MUTATIONS; THERAPY; TRIAL; LEUKEMIA AB Purpose: To estimate the maximum tolerated dose (MTD) for continuous oral administration of the gamma-secretase inhibitor PF-03084014, determine the recommended phase II dose (RP2D), and evaluate safety and preliminary activity in patients with advanced solid tumors. Experimental Design: This open-label, phase I study consisted of a dose-finding portion based on a 3+3 design, followed by an expansion cohort. PF-03084014 was administered orally, twice daily (BID) for 21 continuous days. Tested doses ranged from 20 to 330 mg BID. In the expansion cohort, patients were to receive the estimated MTD or a lower dose of PF-03084014. Results: A total of 64 patients received treatment. The MTD was estimated to be 220 mg BID. The RP2D was determined to be 150 mg BID, based on the better safety profile versus the 220-mg BID dose, given comparable NOTCH-related target inhibition. The most common treatment-related adverse events were diarrhea, nausea, fatigue, hypophosphatemia, vomiting, rash, and decreased appetite, which were generally mild to moderate in severity. One patient with advanced thyroid cancer had a complete response, and five of seven response-evaluable patients with desmoid tumor achieved a partial response (71.4% objective response rate). Tumor responses were mostly durable, ranging from 1.74+ to 24+ months. PF-03084014 demonstrated a generally dose-dependent pharmacokinetic profile at doses ranging from 20 to 330 mg BID. Consistent downmodulation of NOTCH related HES4 gene expression was observed in peripheral blood from all evaluable patients. Conclusion: Further development of PF-03084014 for the treatment of patients with advanced solid tumors is warranted and currently under evaluation. (C) 2014 AACR. C1 [Messersmith, Wells A.; Jimeno, Antonio; Dasari, Arvind] Univ Colorado, Ctr Canc, Aurora, CO 80045 USA. [Shapiro, Geoffrey I.; Cleary, James M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Huang, Bo; Shaik, M. Naveed; Zheng, Xianxian; Reynolds, Jennifer M.; English, Patricia A.; McLachlan, Karen R.; Kern, Kenneth A.] Pfizer Oncol, San Diego, CA USA. [Huang, Bo; Shaik, M. Naveed; Zheng, Xianxian; Reynolds, Jennifer M.; English, Patricia A.; McLachlan, Karen R.; Kern, Kenneth A.] Pfizer Oncol, Groton, CT USA. [Cesari, Rossano] Pfizer Oncol, Milan, Italy. [LoRusso, Patricia M.] Karmanos Canc Inst, Detroit, MI USA. RP Messersmith, WA (reprint author), Univ Colorado, Ctr Canc, 12801 East 17th Ave L18-8121,MS8117, Aurora, CO 80045 USA. EM Wells.Messersmith@ucdenver.edu FU Pfizer Inc. FX This work was sponsored by Pfizer Inc. NR 30 TC 33 Z9 33 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2015 VL 21 IS 1 BP 60 EP 67 DI 10.1158/1078-0432.CCR-14-0607 PG 8 WC Oncology SC Oncology GA AY3CQ UT WOS:000347462600010 PM 25231399 ER PT J AU Shapiro, GI Kwak, E Dezube, BJ Yule, M Ayrton, J Lyons, J Mahadevan, D AF Shapiro, Geoffrey I. Kwak, Eunice Dezube, Bruce J. Yule, Murray Ayrton, John Lyons, John Mahadevan, Daruka TI First-in-Human Phase I Dose Escalation Study of a Second-Generation Non-Ansamycin HSP90 Inhibitor, AT13387, in Patients with Advanced Solid Tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID PROTEIN 90 INHIBITOR; CELL LUNG-CANCER; MOLECULAR CHAPERONE; GANETESPIB STA-9090; CLINICAL-TRIALS; MALIGNANCIES; IMATINIB; MODELS; GROWTH; VITRO AB Purpose: AT13387 is a potent second-generation, fragmentderived HSP90 inhibitor. This phase I study investigated the maximum tolerated dose (MTD)/recommended phase II dose (RP2D) and safety, pharmacokinetic, and pharmacodynamic profiles of two AT13387 regimens in a refractory solid tumor population. Experimental Design: Standard 3-3 dose escalation was used. MTD and RP2D determinations were based on the occurrence of dose-limiting toxicities (DLT) and overall toxicity, respectively. Pharmacokinetic parameters were measured after single and multiple doses. AT13387-mediated induction of HSP70 was evaluated in plasma, peripheral blood mononuclear cells, and paired tumor biopsies. Results: Sixty-two patients were treated with doses ranging from 10 to 120 mg/m(2) twice weekly and 150 to 310 mg/m(2) once weekly (both for 3 weeks every 28 days). One DLT of visual disturbance occurred at 120 mg/m(2), which was considered the MTD and RP2D for the twice-weekly regimen. No formal DLTs occurred in the once-weekly regimen, but multiple moderately severe toxicities, including diarrhea, nausea, vomiting, fatigue, and systemic infusion reactions, led to selection of 260 mg/m(2) as the RP2D. Exposures of AT13387 increased proportionally with dose. Target engagement as measured by HSP70 induction occurred in plasma and tumor biopsy samples. One patient with gastrointestinal stromal tumor (GIST) who had progressive disease on imatinib had a partial response and remained on treatment for 10 months. Twenty-one patients (34%) had stable disease, which lasted > 120 days in 7 patients. Conclusion: AT13387 administered once or twice weekly has an acceptable safety profile and demonstrated evidence of target engagement and preliminary antitumor activity. C1 [Shapiro, Geoffrey I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Shapiro, Geoffrey I.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Shapiro, Geoffrey I.; Kwak, Eunice; Dezube, Bruce J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Kwak, Eunice] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Dezube, Bruce J.] Beth Israel Deaconess Med Sch, Dept Med, Boston, MA USA. [Yule, Murray; Ayrton, John; Lyons, John] Astex Pharmaceut Inc, Dublin, CA USA. [Mahadevan, Daruka] Arizona Canc Ctr, Tucson, AZ USA. RP Shapiro, GI (reprint author), Dana Farber Canc Inst, Early Drug Dev Ctr, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM geoffrey_shapiro@dfciharvard.edu; dmahadevan@WESTCLINIC.com FU Astex Pharmaceuticals, Inc. FX This study was sponsored, monitored, and funded by Astex Pharmaceuticals, Inc. (formerly SuperGen, Inc.). NR 32 TC 14 Z9 15 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2015 VL 21 IS 1 BP 87 EP 97 DI 10.1158/1078-0432.CCR-14-0979 PG 11 WC Oncology SC Oncology GA AY3CQ UT WOS:000347462600013 PM 25336693 ER PT J AU Trabucco, SE Gerstein, RM Evens, AM Bradner, JE Shultz, LD Greiner, DL Zhang, H AF Trabucco, Sally E. Gerstein, Rachel M. Evens, Andrew M. Bradner, James E. Shultz, Leonard D. Greiner, Dale L. Zhang, Hong TI Inhibition of Bromodomain Proteins for the Treatment of Human Diffuse Large B- cell Lymphoma SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENE; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; NON-HODGKIN-LYMPHOMA; C-MYC; SELECTIVE-INHIBITION; SOMATIC MUTATIONS; BET BROMODOMAINS; EXPRESSION; BCL6 AB Purpose: Approximately 50% of patients with diffuse large Bcell lymphoma (DLBCL) enter long-term remission after standard chemotherapy. Patients with DLBCL who do not respond to chemotherapy have few treatment options. There remains a critical need to identify effective and targeted therapeutics for DLBCL. Experimental Design: Recent studies have highlighted the incidence of increased c-MYC protein in DLBCL and the correlation between high levels of c-MYC protein and poor survival prognosis of patients with DLBCL, suggesting that c-MYC is a compelling target for DLBCL therapy. The small molecule JQ1 suppresses c-MYC expression through inhibition of the bromodomain and extra-terminal (BET) family of bromodomain proteins. We investigated whether JQ1 can inhibit proliferation of DLBCL cells in culture and xenograft models in vivo. Results: We show that JQ1 at nanomolar concentrations efficiently inhibited proliferation of human DLBCL cells in a dosedependent manner regardless of their molecular subtypes, suggesting a broad effect of JQ1 in DLBCL. The initial G(1) arrest induced by JQ1 treatment in DLBCL cells was followed by either apoptosis or senescence. The expression of c-MYC was suppressed as a result of JQ1 treatment from the natural, chromosomally translocated, or amplified loci. Furthermore, JQ1 treatment significantly suppressed growth of DLBCL cells engrafted in mice and improved survival of engrafted mice. Conclusion: Our results demonstrate that inhibition of the BET family of bromodomain proteins by JQ1 has potential clinical use in the treatment of DLBCL. C1 [Trabucco, Sally E.; Zhang, Hong] Univ Massachusetts, Sch Med, Dept Cell & Dev Biol, Worcester, MA 01655 USA. [Gerstein, Rachel M.] Univ Massachusetts, Sch Med, Dept Microbiol & Physiol Syst, Worcester, MA 01655 USA. [Evens, Andrew M.] Tufts Med Ctr, Div Hematol & Oncol, Boston, MA USA. [Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Shultz, Leonard D.] Jackson Lab, Bar Harbor, ME 04609 USA. [Greiner, Dale L.] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01655 USA. RP Zhang, H (reprint author), Univ Massachusetts, Sch Med, Dept Cell & Dev Biol, Worcester, MA 01655 USA. EM hong.zhang@umassmed.edu FU NIH [AI046629, CA034196, CA131210] FX This work was supported by NIH research grants AI046629 (D.L. Greiner and L.D. Shultz), CA034196 (L.D. Shultz), and CA131210 (H. Zhang). NR 50 TC 38 Z9 39 U1 3 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2015 VL 21 IS 1 BP 113 EP 122 DI 10.1158/1078-0432.CCR-13-3346 PG 10 WC Oncology SC Oncology GA AY3CQ UT WOS:000347462600016 PM 25009295 ER PT J AU Katayama, R Kobayashi, Y Friboulet, L Lockerman, EL Koike, S Shaw, AT Engelman, JA Fujita, N AF Katayama, Ryohei Kobayashi, Yuka Friboulet, Luc Lockerman, Elizabeth L. Koike, Sumie Shaw, Alice T. Engelman, Jeffrey A. Fujita, Naoya TI Cabozantinib Overcomes Crizotinib Resistance in ROS1 Fusion-Positive Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; KINASE INHIBITOR; CONFER RESISTANCE; ALK INHIBITORS; MUTATIONS; FORETINIB; MUTAGENESIS; DASATINIB; CERITINIB; NILOTINIB AB Purpose: ROS1 rearrangement leads to constitutive ROS1 activation with potent transforming activity. In an ongoing phase I trial, the ALK tyrosine kinase inhibitor (TKI) crizotinib shows remarkable initial responses in patients with non-small cell lung cancer (NSCLC) harboring ROS1 fusions; however, cancers eventually develop crizotinib resistance due to acquired mutations such as G2032R in ROS1. Thus, understanding the crizotinib-resistance mechanisms in ROS1-rearranged NSCLC and identification of therapeutic strategies to overcome the resistance are required. Experimental Design: The sensitivity of CD74-ROS1-transformed Ba/F3 cells to multiple ALK inhibitors was examined. Acquired ROS1 inhibitor-resistant mutations in CD74-ROS1 fusion were screened by N-ethyl-N-nitrosourea mutagenesis with Ba/F3 cells. To overcome the resistance mutation, we performed high-throughput drug screening with small-molecular inhibitors and anticancer drugs used in clinical practice or being currently tested in clinical trials. The effect of the identified drug was assessed in the CD74-ROS1-mutant Ba/F3 cells and crizotinib-resistant patient-derived cancer cells (MGH047) harboring G2032R-mutated CD74-ROS1. Results: We identified multiple novel crizotinib-resistance mutations in the ROS1 kinase domain, including the G2032R mutation. As the result of high-throughput drug screening, we found that the cMET/RET/VEGFR inhibitor cabozantinib (XL184) effectively inhibited the survival of CD74-ROS1 wild-type (WT) and resistant mutants harboring Ba/F3 and MGH047 cells. Furthermore, cabozantinib could overcome all the resistance by all newly identified secondary mutations. Conclusions: We developed a comprehensive model of acquired resistance to ROS1 inhibitors in NSCLC with ROS1 rearrangement and identified cabozantinib as a therapeutic strategy to overcome the resistance. (C) 2014 AACR. C1 [Katayama, Ryohei; Kobayashi, Yuka; Koike, Sumie; Fujita, Naoya] Japanese Fdn Canc Res, Ctr Canc Chemotherapy, Div Expt Chemotherapy, Tokyo 1358550, Japan. [Kobayashi, Yuka; Fujita, Naoya] Univ Tokyo, Grad Sch Frontier Sci, Dept Med Genome Sci, Tokyo, Japan. [Friboulet, Luc; Lockerman, Elizabeth L.; Shaw, Alice T.; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Friboulet, Luc; Lockerman, Elizabeth L.; Shaw, Alice T.; Engelman, Jeffrey A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Fujita, N (reprint author), Japanese Fdn Canc Res, Ctr Canc Chemotherapy, Koto Ku, 3-8-31 Ariake, Tokyo 1358550, Japan. EM naoya.fujita@jfcr.or.jp RI friboulet, luc/N-7276-2015 OI friboulet, luc/0000-0002-1129-4978 FU Japan Society for the Promotion of Science (JSPS) KAKENHI [24300344, 22112008, 25710015]; NIH [R01CA164273]; Princess Takamatsu Cancer Research Fund FX The study was supported, in part, by Japan Society for the Promotion of Science (JSPS) KAKENHI grant numbers 24300344 and 22112008 (to N. Fujita) and 25710015 (to R. Katayama), by NIH grant R01CA164273 (to A.T. Shaw and J.A. Engelman), and by a research grant from the Princess Takamatsu Cancer Research Fund (to N. Fujita). NR 24 TC 24 Z9 26 U1 3 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2015 VL 21 IS 1 BP 166 EP 174 DI 10.1158/1078-0432.CCR-14-1385 PG 9 WC Oncology SC Oncology GA AY3CQ UT WOS:000347462600021 PM 25351743 ER PT J AU Weisman, JS Rodebaugh, TL Brown, PJ Mulligan, EA AF Weisman, Jaclyn S. Rodebaugh, Thomas L. Brown, Patrick J. Mulligan, Elizabeth A. TI Positive Affect and Social Anxiety Across the Lifespan: An Investigation of Age as a Moderator SO CLINICAL GERONTOLOGIST LA English DT Article DE social phobia; aging; positive affect; anxiety disorders; social anxiety ID NEGATIVE AFFECT; OLDER-ADULTS; GERIATRIC DEPRESSION; SUBSYNDROMAL DEPRESSION; PREVALENCE; VALIDATION; DISORDERS; SCALE; METAANALYSIS; INVENTORY AB Recent literature has supported a moderate, inverse relationship between social anxiety and positive affect. It has been proposed, but not clearly established, that the inverse relationship between the constructs may be stronger in younger adults than in adults who are older. We tested this hypothesis in two archival data sets of community participants. The expected age-related interaction was not found in Study 1, which used a measure capturing a conflation of valence and arousal known as activated positive affect. Conversely, the interaction was present in Study 2, in which the positive affect measure was primarily based on valence. We found only partial support for the hypothesis, and results highlight the need for a more comprehensive measure of positive affect. C1 [Weisman, Jaclyn S.; Rodebaugh, Thomas L.] Washington Univ, St Louis, MO 63130 USA. [Brown, Patrick J.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Brown, Patrick J.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Mulligan, Elizabeth A.] VA Boston Healthcare Syst, Brockton, MA USA. RP Weisman, JS (reprint author), Washington Univ, Dept Psychol, 1 Brookings Dr,Campus Box 1125,Psychol Bldg, St Louis, MO 63130 USA. EM weismanj@wustl.edu FU National Institute of Aging [5 T32AG0030]; National Institute of Mental Health [T32 MH20004]; Washington University FX This research was supported by grants from the National Institute of Aging (grant number 5 T32AG0030) and the National Institute of Mental Health (grant number T32 MH20004), as well as a Washington University dissertation fellowship. NR 54 TC 0 Z9 0 U1 3 U2 7 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 2015 VL 38 IS 1 BP 1 EP 18 DI 10.1080/07317115.2014.970317 PG 18 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA AY6ST UT WOS:000347696600001 PM 27642226 ER PT J AU Hesketh, RL Zhu, AX Oklu, R AF Hesketh, Richard L. Zhu, Andrew X. Oklu, Rahmi TI Radiomics and circulating tumor cells: personalized care in hepatocellular carcinoma? SO DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY LA English DT Review ID GENE-EXPRESSION PROGRAMS; RECURRENT MUTATIONS; RANDOMIZED-TRIALS; SOMATIC MUTATIONS; LIVER-CANCER; SERUM; SURVIVAL; HEPATOCARCINOGENESIS; SPECTROSCOPY; METAANALYSIS AB Personalized care in oncology is expected to significantly improve morbidity and mortality, facilitated by our increasing understanding of the molecular mechanisms driving tumors and the ability to target those drivers. Hepatocellular carcinoma has a very high mortality to incidence ratio despite localized disease being curable, emphasizing the importance of early diagnosis. Radiomics, the use of imaging technology to extrapolate molecular tumor data, and the detection of circulating tumor cells (CTCs) are two new technologies that could be incorporated into the clinical setting with relative ease. Here we discuss the molecular mechanisms leading to the development of hepatocellular carcinoma focusing on the latest developments in liver magnetic resonance imaging, CTC, and radiomic technology and their potential to improve diagnosis, staging, and therapy. C1 [Hesketh, Richard L.] West Middlesex Univ Hosp, London, England. [Zhu, Andrew X.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Hematol & Oncol, Boston, MA USA. [Oklu, Rahmi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Imaging & Intervent, Boston, MA 02130 USA. RP Oklu, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Imaging & Intervent, Boston, MA 02130 USA. EM roklu@mgh.harvard.edu FU NCI NIH HHS [R03 CA172738] NR 48 TC 0 Z9 0 U1 4 U2 21 PU AVES PI SISLI PA BUYUKDERE CAD 105-9, MECIDIYEKOY, SISLI, ISTANBUL 34394, TURKEY SN 1305-3825 EI 1305-3612 J9 DIAGN INTERV RADIOL JI Diagn. Interv. Radiol. PD JAN-FEB PY 2015 VL 21 IS 1 DI 10.5152/dir.2014.14237 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AY2IB UT WOS:000347411200013 PM 25430530 ER PT J AU Wang, J Vodovotz, Y Fan, LY Li, YH Liu, Z Namas, R Barclay, D Zamora, R Billiar, TR Wilson, MA Fan, J Jiang, Y AF Wang, Juan Vodovotz, Yoram Fan, Liyan Li, Yuehua Liu, Zheng Namas, Rami Barclay, Derek Zamora, Ruben Billiar, Timothy R. Wilson, Mark A. Fan, Jie Jiang, Yong TI Injury-induced MRP8/MRP14 stimulates IP-10/CXCL10 in monocytes/macrophages SO FASEB JOURNAL LA English DT Article DE IFN regulatory factor 3; myeloid-related protein; Toll-like receptor 4 ID NF-KAPPA-B; INDUCIBLE PROTEIN-10 PRODUCTION; DOUBLE-STRANDED-RNA; TOLL-LIKE RECEPTORS; REGULATORY T-CELLS; IFN-GAMMA; ENDOTHELIAL-CELLS; TNF-ALPHA; CPG OLIGODEOXYNUCLEOTIDES; NEUTROPHIL MIGRATION AB Trauma/hemorrhagic shock is associated with morbidity and mortality due to dysregulated inflammation, which is driven in part by monocytes/macrophages stimulated by injury-induced release of damage-associated molecular pattern (DAMP) molecules. MRP8/MRP14 is an endogenous DAMP involved in various inflammatory diseases, though its mechanism of action is unclear. Circulating MRP8/MRP14 levels in human blunt trauma nonsurvivors were significantly lower than those of survivors (P < 0.001). Human monocytic THP-1 cells stimulated with MRP8/MRP14 expressed the chemokine IFN-gamma inducible protein 10 (IP-10)/CXCL10. Circulating IP-10 levels in human blunt trauma patients were correlated positively with MRP8/MRP14 levels (r = 0.396, P < 0.001), and were significantly lower in trauma nonsurvivors than in survivors (P < 0.001). We therefore sought to determine the mechanisms by which MRP8/MRP14 stimulates IP-10 in monocytes/macrophages, and found that induction of IP-10 by MRP8/MRP14 required Toll-like receptor 4 and TRIF but not MyD88. Full induction of IP-10 by MRP8/MRP14 required synergy between the transcription factors NF-kappa B and IFN regulatory factor 3 (IRF3). The receptor for IP-10 is CXCR3, and MRP8/MRP14-induced chemotaxis of CXCR3(+) cells was dependent on the production of IP-10 in monocytes/macrophages. Furthermore, in vivo study with a mouse trauma/hemorrhagic shock model showed that administration of neutralizing antibody against MRP8 prevented activation of NF-kB and IRF3 as well as IP-10 production. Thus, the current study identified a novel signaling mechanism that controls IP-10 expression in monocytes/macrophages by MRP8/MRP14, which may play an important role in injury-induced inflammation. C1 [Wang, Juan; Liu, Zheng; Fan, Jie; Jiang, Yong] Southern Med Univ, State Key Lab Organ Failure Res, Key Lab Transcript & Prote, Minist Educ China,Key Lab Prote Guangdong Prov, Guangzhou 510515, Guangdong, Peoples R China. [Wang, Juan; Vodovotz, Yoram; Li, Yuehua; Namas, Rami; Barclay, Derek; Zamora, Ruben; Billiar, Timothy R.; Wilson, Mark A.; Fan, Jie] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA. [Wilson, Mark A.; Fan, Jie] Vet Affairs Pittsburgh Healthcare Syst, Res & Dev, Pittsburgh, PA USA. [Fan, Liyan] Univ Pittsburgh, Sch Arts & Sci, Pittsburgh, PA USA. [Vodovotz, Yoram; Billiar, Timothy R.; Fan, Jie] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA USA. RP Jiang, Y (reprint author), Southern Med Univ, Dept Pathophysiol, Guangzhou 510515, Guangdong, Peoples R China. EM jif7@pitt.edu; jiang48231@163.com OI Namas, Rami/0000-0002-8582-5321 FU BLRD VA [I01 BX002729]; NHLBI NIH HHS [R01 HL079669, R01-HL-079669]; NIGMS NIH HHS [P50 GM053789, P50-GM-53789] NR 60 TC 11 Z9 12 U1 0 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD JAN PY 2015 VL 29 IS 1 BP 250 EP 262 DI 10.1096/fj.14-255992 PG 13 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA AY1UX UT WOS:000347378600024 PM 25342131 ER PT J AU Markland, A Wang, L Jelovsek, JE Brubaker, L Tuteja, A Weidner, AC LoSavio, A Corton, M Meikle, S Richter, HE AF Markland, Alayne Wang, Lu Jelovsek, J. Eric Brubaker, Linda Tuteja, Ashook Weidner, Alison C. LoSavio, Andelka Corton, Marlene Meikle, Susan Richter, Holly E. TI Symptom Improvement in Women After Fecal Incontinence Treatments: A Multicenter Cohort Study of the Pelvic Floor Disorders Network SO FEMALE PELVIC MEDICINE AND RECONSTRUCTIVE SURGERY LA English DT Article DE fecal incontinence; cohort study; surgical treatment; nonsurgical treatment; quality of life ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; BIOFEEDBACK; QUESTIONNAIRE; EPIDEMIOLOGY; POPULATION; OUTCOMES; PATIENT; ADULTS AB Objectives: The study aims were to characterize women with fecal incontinence (FI) and measure changes in FI severity and quality of life 3 and 12 months after treatment. Methods: This study is a secondary analysis of a multicenter study measuring adaptive behaviors among women with FI. Women included had a primary complaint of at least monthly FI over 3 consecutive months and planned FI treatment. Demographic and medical history data were obtained at baseline. Data were collected at baseline, 3 months, and 12 months after clinically selected, nonstandardized treatment. Validated questionnaires were as follows: Fecal Incontinence Severity Index, Modified Manchester Health Questionnaire, Pelvic Floor Disorders Inventory's Colorectal and Anal Distress Inventory, Pelvic Floor Impact Questionnaire's Colorectal and Anal Impact Questionnaire, and Medical Outcomes Study Short Form. Questionnaire score changes from baseline were compared using paired t tests at 3 and 12 months after treatment. Results: Of the 133 women enrolled, 90 women had treatment data at 3 months and 77 at 12 months. Nonsurgical therapies were the most common (78%) with anal sphincter repair in 22%. Fecal Incontinence Severity Index scores and Modified Manchester Health Questionnaire scores significantly improved 3 months after nonsurgical and surgical treatments (-8.8 +/- 12.0 and -12.6 +/- 19.2, respectively, P < 0.001), as did Colorectal-Anal Distress Inventory and Colorectal-Anal Impact Questionnaire scores (-52.7 +/- 70.0 and -60.6 +/- 70.0, respectively, P < 0.001) and Medical Outcomes Study Short Form mental health scores (4.2 +/- 9.4, P = 0.001). Improvement persisted 12 months posttreatment. Conclusions: In women seeking care for FI, symptom severity and condition-specific quality of life significantly improve within the first 3 months after FI treatment and are maintained up to 12 months. C1 [Markland, Alayne] Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Wang, Lu] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Jelovsek, J. Eric] Cleveland Clin, Dept Obstet Gynecol, Cleveland, OH 44106 USA. [Jelovsek, J. Eric] Cleveland Clin, Womens Hlth Inst, Cleveland, OH 44106 USA. [Brubaker, Linda] Loyola Univ Chicago, Stritch Sch Med, Dept Obstet & Gynecol, Chicago, IL USA. [Tuteja, Ashook] Univ Utah, Salt Lake City Vet Affairs Med Ctr, Dept Med, Salt Lake City, UT USA. [Weidner, Alison C.] Duke Univ, Dept Obstet & Gynecol, Durham, NC USA. [LoSavio, Andelka] Loyola Univ Chicago, Stritch Sch Med, Dept Med, Chicago, IL USA. [Corton, Marlene] Univ Texas Southwestern, Dept Obstet & Gynecol, Dallas, TX USA. [Meikle, Susan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Richter, Holly E.] Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL USA. RP Markland, A (reprint author), Birmingham Vet Affairs Med Ctr, Dept Med, Div Gerontol Geriatr & Palliat Care, GRECC 11-G,Room 8220,700 South 19th St, Birmingham, AL 35233 USA. EM amarkland@uabmc.edu OI Markland, Alayne/0000-0002-6567-6744 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health Office of Research on Women's Health [U01 HD41249, U10 HD41250, U10 HD41261, U10 HD41267, U10 HD54136, U10 HD54214, U10 HD54215, U10 HD54241] FX Supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Research on Women's Health (U01 HD41249, U10 HD41250, U10 HD41261, U10 HD41267, U10 HD54136, U10 HD54214, U10 HD54215, and U10 HD54241). NR 29 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2151-8378 EI 2154-4212 J9 FEMALE PELVIC MED RE JI Female Pelvic Med. Reconstr. Surg. PD JAN-FEB PY 2015 VL 21 IS 1 BP 46 EP 52 DI 10.1097/SPV.0000000000000099 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AY3DN UT WOS:000347464800015 PM 25185613 ER PT J AU Yeo, NC O'Meara, CC Bonomo, JA Veth, KN Tomar, R Flister, MJ Drummond, IA Bowden, DW Freedman, BI Lazar, J Link, BA Jacob, HJ AF Yeo, Nan Cher O'Meara, Caitlin C. Bonomo, Jason A. Veth, Kerry N. Tomar, Ritu Flister, Michael J. Drummond, Iain A. Bowden, Donald W. Freedman, Barry I. Lazar, Jozef Link, Brian A. Jacob, Howard J. TI Shroom3 contributes to the maintenance of the glomerular filtration barrier integrity SO GENOME RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; CHRONIC KIDNEY-DISEASE; FAWN-HOODED RAT; RENAL-DISEASE; UNILATERAL NEPHRECTOMY; MODULATES PROTEINURIA; MISSING HERITABILITY; APICAL CONSTRICTION; COMPLEX DISEASES; ZEBRAFISH AB Genome-wide association studies (GWAS) identify regions of the genome correlated with disease risk but are restricted in their ability to identify the underlying causative mechanism(s). Thus, GWAS are useful "roadmaps" that require functional analysis to establish the genetic and mechanistic structure of a particular locus. Unfortunately, direct functional testing in humans is limited, demonstrating the need for complementary approaches. Here we used an integrated approach combining zebrafish, rat, and human data to interrogate the function of an established GWAS locus (SHROOM3) lacking prior functional support for chronic kidney disease (CKD). Congenic mapping and sequence analysis in rats suggested Shroom3 was a strong positional candidate gene. Transferring a 6.1-Mb region containing the wild-type Shroom3 gene significantly improved the kidney glomerular function in FHH (fawn-hooded hypertensive) rat. The wild-type Shroom3 allele, but not the FHH Shroom3 allele, rescued glomerular defects induced by knockdown of endogenous shroom3 in zebrafish, suggesting that the FHH Shroom3 allele is defective and likely contributes to renal injury in the FHH rat. We also show for the first time that variants disrupting the actin-binding domain of SHROOM3 may cause podocyte effacement and impairment of the glomerular filtration barrier. C1 [Yeo, Nan Cher; O'Meara, Caitlin C.; Flister, Michael J.; Lazar, Jozef; Jacob, Howard J.] Med Coll Wisconsin, Human & Mol Genet Ctr, Milwaukee, WI 53226 USA. [Yeo, Nan Cher; O'Meara, Caitlin C.; Flister, Michael J.; Jacob, Howard J.] Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA. [Bonomo, Jason A.] Wake Forest Univ, Bowman Gray Sch Med, Dept Mol Med & Translat Sci, Winston Salem, NC 27157 USA. [Bonomo, Jason A.; Bowden, Donald W.; Freedman, Barry I.] Wake Forest Univ, Bowman Gray Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC 27157 USA. [Veth, Kerry N.; Link, Brian A.] Med Coll Wisconsin, Dept Cell Biol Neurobiol & Anat, Milwaukee, WI 53226 USA. [Tomar, Ritu; Drummond, Iain A.] Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA 02129 USA. [Drummond, Iain A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Bowden, Donald W.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biochem, Winston Salem, NC 27157 USA. [Freedman, Barry I.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med Nephrol, Winston Salem, NC 27157 USA. [Lazar, Jozef] Med Coll Wisconsin, Dept Dermatol, Milwaukee, WI 53226 USA. [Jacob, Howard J.] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA. RP Jacob, HJ (reprint author), Med Coll Wisconsin, Human & Mol Genet Ctr, Milwaukee, WI 53226 USA. EM jacob@mcw.edu FU NIH [RO1HL069321, RO1-DK071041, RO1-DK53591, RO1-DK070941, RO1-DK071891]; [F30 DK098836] FX We thank M. Hoffman, C. Purman, M. Cliff, A. Buzzell, A. Lemke, J. Wendt-Andrae, and B. Schilling for excellent technical support; C. Wells for help with electron microscopic imaging; and NIH grant support RO1HL069321 (H.J.J.), RO1-DK071041 (I.A.D.), RO1-DK53591 (D.W.B.), RO1-DK070941 (B.I.F.), and RO1-DK071891 (B.I.F.). J.A.B. is supported by F30 DK098836. This project was conceived and directed by H.J.J. NR 49 TC 8 Z9 8 U1 1 U2 7 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD JAN PY 2015 VL 25 IS 1 BP 57 EP 65 DI 10.1101/gr.182881.114 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA AY1SW UT WOS:000347373200005 PM 25273069 ER PT J AU Michmizos, KP Frangou, P Stathis, P Sakas, D Nikita, KS AF Michmizos, Konstantinos P. Frangou, Polytimi Stathis, Pantelis Sakas, Damianos Nikita, Konstantina S. TI Beta-Band Frequency Peaks Inside the Subthalamic Nucleus as a Biomarker for Motor Improvement After Deep Brain Stimulation in Parkinson's Disease SO IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS LA English DT Article DE Beta-band oscillations; clinical biomarker; deep brain stimulation (DBS); neuromodulation; Parkinson's disease (PD) ID TECHNICAL APPROACH; GLOBUS-PALLIDUS; OSCILLATIONS; MODEL; RECORDINGS; SYNCHRONIZATION; IDENTIFICATION; IMPLANTATION; PREDICTS; SURGERY AB Deep brain stimulation (DBS) of the subthalamic nucleus (STN) remains an empirical, yet highly effective, surgical treatment for advanced Parkinson's disease (PD). DBS outcome depends on accurate stimulation of the STN sensorimotor area which is a trial-and-error procedure taking place during and after surgery. Pathologically enhanced beta-band (13-35 Hz) oscillatory activity across the cortico-basal ganglia pathways is a prominent neurophysiological phenomenon associated with PD. We hypothesized that weighing together beta-band frequency peaks from simultaneous microelectrode recordings in "off-state" PD patients could map the individual neuroanatomical variability and serve as a biomarker for the location of the STN sensorimotor neurons. We validated our hypothesis with 9 and 11 patients that, respectively, responded well and poorly to bilateral DBS, after at least two years of follow up. We categorized "good" and "poor" DBS responders based on their clinical assessment alongside a > 40% and < 30% change, respectively, in "off" unified PD rating scale motor scores. Good (poor) DBS responders had, in average, 1 mm (3.5 mm) vertical distance between the maximum beta-peak weighted across the parallel microelectrodes and the center of the stimulation area. The distances were statistically different in the two groups (p = 0.0025). Our biomarker could provide personalized intra-and postoperative support in stimulating the STN sensorimotor area associated with optimal long-term clinical benefits. C1 [Michmizos, Konstantinos P.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Michmizos, Konstantinos P.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Michmizos, Konstantinos P.] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Frangou, Polytimi] Univ Cambridge, Dept Psychol, Adapt Brain Lab, Cambridge CB2 1TN, England. [Stathis, Pantelis] Mediterraneo Hosp, Dept Neurol, Athens 16675, Greece. [Stathis, Pantelis; Sakas, Damianos] Univ Athens, Evangelismos Gen Hosp, Dept Neurosurg, Athens 11527, Greece. [Nikita, Konstantina S.] Natl Tech Univ Athens, Fac Elect & Comp Engn, Biomed Simulat & Imaging Lab, GR-10682 Athens, Greece. RP Michmizos, KP (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. EM konmic@mgh.harvard.edu; pf319@cam.ac.uk; stathis.pantelis@gmail.com; sakasde@med.uoa.gr; knikita@ece.ntua.gr NR 52 TC 3 Z9 3 U1 1 U2 12 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 2168-2194 J9 IEEE J BIOMED HEALTH JI IEEE J. Biomed. Health Inform. PD JAN PY 2015 VL 19 IS 1 BP 174 EP 180 DI 10.1109/JBHI.2014.2344102 PG 7 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Mathematical & Computational Biology; Medical Informatics GA AY1GP UT WOS:000347342300022 PM 25095273 ER PT J AU Valenza, G Citi, L Gentili, C Lanata, A Scilingo, EP Barbieri, R AF Valenza, Gaetano Citi, Luca Gentili, Claudio Lanata, Antonio Scilingo, Enzo Pasquale Barbieri, Riccardo TI Characterization of Depressive States in Bipolar Patients Using Wearable Textile Technology and Instantaneous Heart Rate Variability Assessment SO IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS LA English DT Article DE Bipolar disorder; bispectrum; heart rate variability (HRV); high-order statistics; mood recognition; nonlinear ID AUTONOMIC NERVOUS-SYSTEM; RATE CIRCADIAN-RHYTHM; MAJOR DEPRESSION; DISORDER; METAANALYSIS; RECOGNITION; BISPECTRUM; MARKER; STIMULATION; ASSOCIATION AB The analysis of cognitive and autonomic responses to emotionally relevant stimuli could provide a viable solution for the automatic recognition of different mood states, both in normal and pathological conditions. In this study, we present a methodological application describing a novel system based on wearable textile technology and instantaneous nonlinear heart rate variability assessment, able to characterize the autonomic status of bipolar patients by considering only electrocardiogram recordings. As a proof of this concept, our study presents results obtained fromeight bipolar patients during their normal daily activities and being elicited according to a specific emotional protocol through the presentation of emotionally relevant pictures. Linear and nonlinear features were computed using a novel point-process-based nonlinear autoregressive integrative model and compared with traditional algorithmic methods. The estimated indices were used as the input of a multilayer perceptron to discriminate the depressive from the euthymic status. Results show that our system achieves much higher accuracy than the traditional techniques. Moreover, the inclusion of instantaneous higher order spectra features significantly improves the accuracy in successfully recognizing depression from euthymia. C1 [Valenza, Gaetano; Lanata, Antonio; Scilingo, Enzo Pasquale] Univ Pisa, Res Ctr E Piaggio, I-56100 Pisa, Italy. [Valenza, Gaetano; Lanata, Antonio; Scilingo, Enzo Pasquale] Univ Pisa, Dept Informat Engn, I-56100 Pisa, Italy. [Valenza, Gaetano; Citi, Luca; Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. [Valenza, Gaetano; Citi, Luca; Barbieri, Riccardo] MIT, Cambridge, MA 02139 USA. [Citi, Luca] Univ Essex, Sch Comp Sci & Elect Engn, Colchester CO4 3SQ, Essex, England. [Gentili, Claudio] Univ Pisa, Psychol Sect, Dept Surg Med Mol & Crit Area Pathol, I-56100 Pisa, Italy. RP Valenza, G (reprint author), Univ Pisa, Res Ctr E Piaggio, I-56100 Pisa, Italy. EM g.valenza@ieee.org; lciti@neurostat.mit.edu; claudio.gentili@med.unipi.it; a.lanata@centropiaggio.unipi.it; e.scilingo@centropiaggio.unipi.it; barbieri@neurostat.mit.edu OI Barbieri, Riccardo/0000-0001-9381-3833; Gentili, Claudio/0000-0002-2579-8755; Lanata, Antonio/0000-0002-6540-5952; Scilingo, Enzo Pasquale/0000-0003-2588-4917 FU EU Commission [ICT-247777]; Department of Anesthesia, Critical Care & Pain Medicine, Massachusetts General Hospital; Harvard Medical School, Boston, MA, USA FX This work was supported in part by EU Commission under Contract ICT-247777 Psyche and by the Department of Anesthesia, Critical Care & Pain Medicine, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA. NR 78 TC 19 Z9 19 U1 2 U2 7 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 2168-2194 J9 IEEE J BIOMED HEALTH JI IEEE J. Biomed. Health Inform. PD JAN PY 2015 VL 19 IS 1 BP 263 EP 274 DI 10.1109/JBHI.2014.2307584 PG 12 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Mathematical & Computational Biology; Medical Informatics GA AY1GP UT WOS:000347342300032 PM 25561449 ER PT J AU Yip, M Jin, R Nakajima, HH Stankovic, KM Chandrakasan, AP AF Yip, Marcus Jin, Rui Nakajima, Hideko Heidi Stankovic, Konstantina M. Chandrakasan, Anantha P. TI A Fully-Implantable Cochlear Implant SoC With Piezoelectric Middle-Ear Sensor and Arbitrary Waveform Neural Stimulation SO IEEE JOURNAL OF SOLID-STATE CIRCUITS LA English DT Article; Proceedings Paper CT 1st IEEE International Solid-State Circuits Conference (ISSCC) CY FEB 09-13, 2014 CL San Francisco, CA SP IEEE DE Arbitrary waveform; cochlear implant; energy-efficient; hearing loss; implantable; low-voltage; microphone; middle ear; piezoelectric; reconfigurable; SoC; stimulation; ultra-low-power ID SPEECH RECOGNITION; TEMPORAL CUES; HEARING-LOSS; NUMBER; PERFORMANCE; PERCEPTION; ELECTRODES; RESOLUTION; PROCESSOR; CHANNELS AB A system-on-chip for an invisible, fully-implantable cochlear implant is presented. Implantable acoustic sensing is achieved by interfacing the SoC to a piezoelectric sensor that detects the sound-induced motion of the middle ear. Measurements from human cadaveric ears demonstrate that the sensor can detect sounds between 40 and 90 dB SPL over the speech bandwidth. A highly-reconfigurable digital sound processor enables system power scalability by reconfiguring the number of channels, and provides programmable features to enable a patient-specific fit. A mixed-signal arbitrary waveform neural stimulator enables energy-optimal stimulation pulses to be delivered to the auditory nerve. The energy-optimal waveform is validated with in-vivo measurements from four human subjects which show a 15% to 35% energy saving over the conventional rectangular waveform. Prototyped in a 0.18 mu m high-voltage CMOS technology, the SoC in 8-channel mode consumes 572 mu W of power including stimulation. The SoC integrates implantable acoustic sensing, sound processing, and neural stimulation on one chip to minimize the implant size, and proof-of-concept is demonstrated with measurements from a human cadaver ear. C1 [Yip, Marcus; Jin, Rui; Chandrakasan, Anantha P.] MIT, Microsyst Technol Labs, Cambridge, MA 02139 USA. [Nakajima, Hideko Heidi; Stankovic, Konstantina M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Nakajima, Hideko Heidi; Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Yip, M (reprint author), MIT, Microsyst Technol Labs, Cambridge, MA 02139 USA. EM anantha@mtl.mit.edu FU NSERC; Bertarelli Foundation FX This work was supported by NSERC and the Bertarelli Foundation. NR 24 TC 6 Z9 6 U1 3 U2 10 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9200 EI 1558-173X J9 IEEE J SOLID-ST CIRC JI IEEE J. Solid-State Circuit PD JAN PY 2015 VL 50 IS 1 SI SI BP 214 EP 229 DI 10.1109/JSSC.2014.2355822 PG 16 WC Engineering, Electrical & Electronic SC Engineering GA AX5NG UT WOS:000346972800019 PM 26251552 ER PT J AU Aronis, KN Moreno, M Polyzos, SA Moreno-Navarrete, JM Ricart, W Delgado, E de la Hera, J Sahin-Efe, A Chamberland, JP Berman, R Spiro, A Vokonas, P Fernandez-Real, JM Mantzoros, CS AF Aronis, K. N. Moreno, M. Polyzos, S. A. Moreno-Navarrete, J. M. Ricart, W. Delgado, E. de la Hera, J. Sahin-Efe, A. Chamberland, J. P. Berman, R. Spiro, A., III Vokonas, P. Fernandez-Real, J. M. Mantzoros, C. S. TI Circulating irisin levels and coronary heart disease: association with future acute coronary syndrome and major adverse cardiovascular events SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article ID MESSENGER-RNA EXPRESSION; FATTY LIVER-DISEASE; BODY-MASS INDEX; INSULIN-RESISTANCE; PRECURSOR FNDC5; ADIPOSE-TISSUE; RISK-FACTOR; HUMANS; EXERCISE; MUSCLE AB INTRODUCTION: Irisin is a newly discovered myokine, associated with 'browning' of the white adipose tissue, obesity, insulin resistance and metabolic syndrome. The purpose of this study is to evaluate circulating irisin as a predictor of acute coronary syndromes (ACSs) and major adverse cardiovascular events (MACE). METHODS: Sub-study 1: a case-control study, nested within the Veteran's Affairs Normative Ageing Study, evaluating circulating irisin levels in 88 ACS cases and 158 age-and sampling year-matched controls, as a predictor of ACS. Sub-study 2: a prospective cohort study, where 103 participants with established coronary artery disease were stratified by circulating irisin levels at the time they received percutaneous coronary interventions (PCIs) and were followed for the development of MACE. RESULTS: Study 1: there was no association between irisin levels and ACS in otherwise healthy individuals (odds ratio: 1.00 95% confidence interval: (0.99-1.00)). Study 2: the incidence of MACE was significantly lower in the first irisin tertile compared with the second and third (incidence rate 0 vs 0.92 (0.51-1.61) vs 0.57 (0.28-1.14) events per 1000 person-days; P<0.01). This was primarily driven by the lower incidence of unstable angina (incidence rate 0 vs 0.61 (0.31-1.22) vs 0.43 (0.19-0.96) per 1000 person-days; P = 0.01). CONCLUSION: This is the first study to date that demonstrates that, although circulating irisin levels do not predict the development of ACS in healthy individuals, increased irisin levels are associated with the development of MACE in patients with established coronary artery disease after PCI. C1 [Aronis, K. N.; Sahin-Efe, A.; Chamberland, J. P.; Berman, R.; Mantzoros, C. S.] Harvard Univ, Sch Med, Dept Med, VA Boston Healthcare Syst,Sect Endocrinol, Boston, MA USA. [Aronis, K. N.; Sahin-Efe, A.; Chamberland, J. P.; Berman, R.; Mantzoros, C. S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab,Dept Med, Boston, MA 02215 USA. [Aronis, K. N.] Boston Univ, Dept Med, Boston Med Ctr, Boston, MA 02215 USA. [Moreno, M.; Moreno-Navarrete, J. M.; Ricart, W.] CIBEROBN CB06 03 010, Inst Invest Biomed Girona IdIBGi, Dept Diabet Endocrinol & Nutr, Girona, Spain. [Polyzos, S. A.] Aristotle Univ Thessaloniki, Ippokration Gen Hosp, Med Clin 2, GR-54006 Thessaloniki, Greece. [Delgado, E.; de la Hera, J.; Fernandez-Real, J. M.] Cent Hosp Asturias, Oviedo, Spain. [Spiro, A., III; Vokonas, P.] VA Boston Healthcare Syst, Boston, MA USA. [Spiro, A., III] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Vokonas, P.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Fernandez-Real, JM (reprint author), Hosp Girona Dr Josep Trueta, Sect Diabet Endocrinol & Nutr, Carretera Franca S-N, Girona 17007, Spain. EM jmfreal@idibgi.org RI Delgado, Elias/B-2634-2013; Moreno-Navarrete, Jose Maria/H-9772-2015; Aronis, Konstantinos/F-3586-2012; OI Fernandez-Real, Jose Manuel/0000-0002-7442-9323; Delgado, Elias/0000-0001-6114-9712; Aronis, Konstantinos/0000-0001-7189-8434; Ricart, Wifredo/0000-0002-3452-9098 FU Clinical Science Research and Development Service of the VA Office of Research and Development [1I01CX000422-01A1]; Cooperative Studies Program/ERIC, US Department of Veterans Affairs and is a research component of the Massachusetts Veterans Epidemiology Research and Information Center; Research Career Scientist award from the Clinical Science Research and development service, US department of veterans' affairs; Spanish Ministry of Health [FIS 2011-00214]; CIBERobn Fisiopatologia de la Obesidad y la Nutricion (CIBERobn) FX The Mantzoros Laboratory is supported by Award Number 1I01CX000422-01A1 from the Clinical Science Research and Development Service of the VA Office of Research and Development. NAS is supported by Cooperative Studies Program/ERIC, US Department of Veterans Affairs and is a research component of the Massachusetts Veterans Epidemiology Research and Information Center. Dr Spiro is supported by a Research Career Scientist award from the Clinical Science Research and development service, US department of veterans' affairs. This study was also supported by the Spanish Ministry of Health (FIS 2011-00214) and CIBERobn Fisiopatologia de la Obesidad y la Nutricion (CIBERobn). The CIBER de la Fisiopatologia de la Obesidad y Nutricion (CIBERobn) is an initiative from the Instituto de Salud Carlos III (ISCIII). NR 34 TC 14 Z9 14 U1 3 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 EI 1476-5497 J9 INT J OBESITY JI Int. J. Obes. PD JAN PY 2015 VL 39 IS 1 BP 156 EP 161 DI 10.1038/ijo.2014.101 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA AY2BR UT WOS:000347394000023 PM 24916788 ER PT J AU Gellad, WF Zhao, XH Thorpe, CT Mor, MK Good, CB Fine, MJ AF Gellad, Walid F. Zhao, Xinhua Thorpe, Carolyn T. Mor, Maria K. Good, Chester B. Fine, Michael J. TI Dual Use of Department of Veterans Affairs and Medicare Benefits and Use of Test Strips in Veterans With Type 2 Diabetes Mellitus SO JAMA INTERNAL MEDICINE LA English DT Article ID HEALTH-CARE-SYSTEM; BLOOD-GLUCOSE; PATIENT DATA; INSULIN; QUALITY; VA; METAANALYSIS; ENROLLEES; OUTCOMES; ACCESS AB IMPORTANCE Self-monitoring of blood glucose is a costly component of care for diabetes mellitus, with unclear benefits for patients not taking insulin. Veterans with dual Department of Veterans Affairs (VA) and Medicare benefits have access to test strips through both systems, raising the potential for overuse. OBJECTIVES To examine the patterns of test strip receipt among older veterans with diabetes and determine whether receipt of strips from dual health care systems is associated with overuse. DESIGN, SETTING, AND PARTICIPANTS We performed a cross-sectional, retrospective cohort study using national VA administrative data linked to Medicare Parts A, B, and D claims for fiscal years 2008 and 2009. A total of 363 996 community-dwelling veterans 65 years or older with diabetes who used the VA health care system and received test strips in fiscal year 2009 were included in the study. EXPOSURES Receipt of test strips from the VA only, Medicare only, or both the VA and Medicare; covariates included sociodemographics, comorbidity, diabetes complications, and hemoglobin A(1c) level. MAIN OUTCOMES AND MEASURES Quantity of test strips dispensed and overuse of test strips, defined as more than 1 strip per day (>365 strips per year) among those taking no diabetes medications, oral diabetes medications alone, or long-acting insulin without short-acting insulin or more than 4 strips per day (>1460 strips per year) among those taking short-acting insulin. RESULTS Overall, 260 688 older veterans (71.6%) with diabetes received strips from the VA only, 82 826 (22.8%) from Medicare only, and 20 482 (5.6%) from the VA and Medicare. Veterans receiving strips from both the VA and Medicare received more strips (median, 600; interquartile range [IQR], 350-1000) than the Medicare only (median, 400; IQR, 200-700) and VA only (median, 200; IQR, 100-500) groups (P<.001) and had substantially greater odds of overuse than the VA only group (55.4% vs 15.8%) (adjusted odds ratio [OR], 16.3; 95% CI, 14.6-18.1 for no medications; 55.3% vs 6.0%; OR, 19.8; 95% CI, 18.9-20.8 for oral medications; 87.4% vs 65.5%; OR, 3.69; 95% CI, 3.30-4.14 for long-acting insulin; and 32.8% vs 13.5%; OR, 3.24; 95% CI, 3.05-3.45 for short-acting insulin). Patterns were similar when using more conservative thresholds of overuse. CONCLUSIONS AND RELEVANCE Veterans who receive glucose test strips through both the VA and Medicare use more strips and are more likely to potentially overuse strips. These results illustrate the profound importance of understanding dual VA and Medicare coverage and are emblematic of waste and inefficiency. C1 [Gellad, Walid F.; Zhao, Xinhua; Thorpe, Carolyn T.; Mor, Maria K.; Good, Chester B.; Fine, Michael J.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15240 USA. [Gellad, Walid F.; Good, Chester B.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Med, Pittsburgh, PA 15213 USA. [Thorpe, Carolyn T.; Good, Chester B.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. [Mor, Maria K.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. [Good, Chester B.] US Dept Vet Affairs, Pharm Benefits Management Serv, Hines, IL USA. RP Gellad, WF (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Univ Dr,Mail Code 151C, Pittsburgh, PA 15240 USA. EM walid.gellad@va.gov FU Veterans Affairs Health Services Research & Development Service [CDA 09-207]; Veterans Affairs Center for Health Equity Research and Promotion FX This study was supported by grant CDA 09-207 from the Veterans Affairs Health Services Research & Development Service and from pilot funding from the Veterans Affairs Center for Health Equity Research and Promotion (Dr Gellad). NR 45 TC 6 Z9 6 U1 2 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JAN PY 2015 VL 175 IS 1 BP 26 EP 34 DI 10.1001/jamainternmed.2014.5405 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AY1BM UT WOS:000347328500011 PM 25383920 ER PT J AU Okulicz, JF Le, TD Agan, BK Camargo, JF Landrum, ML Wright, E Dolan, MJ Ganesan, A Ferguson, TM Smith, DM Richman, DD Little, SJ Clark, RA He, WJ Ahuja, SK AF Okulicz, Jason F. Le, Tuan D. Agan, Brian K. Camargo, Jose F. Landrum, Michael L. Wright, Edwina Dolan, Matthew J. Ganesan, Anuradha Ferguson, Tomas M. Smith, Davey M. Richman, Douglas D. Little, Susan J. Clark, Robert A. He, Weijing Ahuja, Sunil K. TI Influence of the Timing of Antiretroviral Therapy on the Potential for Normalization of Immune Status in Human Immunodeficiency Virus 1-Infected Individuals SO JAMA INTERNAL MEDICINE LA English DT Article ID HIV-INFECTED PATIENTS; T-CELL COUNTS; CLINICAL-OUTCOMES; CD4 COUNT; AIDS; RESTORATION; RESERVOIRS; INITIATION; RECOVERY; HAART AB IMPORTANCE In individuals with human immunodeficiency virus 1 (HIV-1) infection who are receiving antiretroviral therapy (ART), factors that promote full immune recovery are not well characterized. OBJECTIVE To investigate the influence of the timing of ART relative to HIV-1 infection on normalization of CD4(+) T-cell counts, AIDS risk, and immune function. DESIGN, SETTING, AND PARTICIPANTS Participants in the observational US Military HIV Natural History Study with documented estimated dates of seroconversion (EDS) who achieved virologic suppression with ART were evaluated. Markers indicative of immune activation, dysfunction, and responsiveness were determined. Responses to hepatitis B virus (HBV) vaccine, an indicator of in vivo immune function, were also assessed. The timing of ART was indexed to the EDS and/or entry into the cohort. The CD4(+) counts in HIV-1-uninfected populations were surveyed. MAIN OUTCOMES AND MEASURES Normalization of CD4(+) counts to 900 cells/mu L or higher, AIDS development, HBV vaccine response, as well as T-cell activation, dysfunction, and responsiveness. RESULTS The median CD4(+) count in HIV-1-uninfected populations was approximately 900 cells/mu L. Among 1119 HIV-1-infected participants, CD4(+) normalization was achieved in 38.4% vs 28.3% of those initiating ART within 12 months vs after 12 months from the EDS (P=.001). Incrementally higher CD4(+) recovery (<500, 500-899, and >= 900 cells/mu L) was associated with stepwise decreases in AIDS risk and reversion of markers of immune activation, dysfunction, and responsiveness to levels approximating those found in HIV-1-uninfected persons. Participants with CD4(+) counts of 500 cells/mu L or higher at study entry (adjusted odds ratio [aOR], 2.00; 95% CI, 1.51-2.64; P<.001) or ART initiation (aOR, 4.08; 95% CI, 3.14-5.30; P<.001) had significantly increased CD4(+) normalization rates compared with other participants. However, even among individuals with a CD4(+) count of 500 cells/mu L or higher at both study entry and before ART, the odds of CD4(+) normalization were 80% lower in those initiating ART after 12 months from the EDS and study entry (aOR, 0.20; 95% CI, 0.07-0.53; P=001). Initiation of ART within 12 months of EDS vs later was associated with a significantly lower risk of AIDS (7.8% vs 15.3%; P=.002), reduced T-cell activation (percent CD4(+) HLA-DR+ effector memory T cells, 12.0% vs 15.6%; P=.03), and increased responsiveness to HBV vaccine (67.9% vs 50.9%; P=.07). CONCLUSIONS AND RELEVANCE Deferral of ART beyond 12 months of the EDS diminishes the likelihood of restoring immunologic health in HIV-1-infected individuals. C1 [Okulicz, Jason F.; Agan, Brian K.; Landrum, Michael L.; Ganesan, Anuradha; Ferguson, Tomas M.] Uniformed Serv Univ Hlth Sci, Infect Dis Clin Res Program, Bethesda, MD 20814 USA. [Okulicz, Jason F.] San Antonio Mil Med Ctr, Infect Dis Serv, Ft Sam Houston, TX USA. [Le, Tuan D.; Camargo, Jose F.; Clark, Robert A.; He, Weijing; Ahuja, Sunil K.] South Texas Vet Hlth Care Syst, Vet Affairs VA Res Ctr AIDS & HIV Infect 1, San Antonio, TX 78229 USA. [Le, Tuan D.; Camargo, Jose F.; Clark, Robert A.; He, Weijing; Ahuja, Sunil K.] South Texas Vet Hlth Care Syst, Vet Affairs Ctr Personalized Med, San Antonio, TX 78229 USA. [Le, Tuan D.; Camargo, Jose F.; Clark, Robert A.; He, Weijing; Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Agan, Brian K.] Henry M Jackson Fdn Adv Mil Med Inc, Bethesda, MD USA. [Landrum, Michael L.] Brooke Army Med Ctr, Infect Dis Serv, Ft Sam Houston, TX 78234 USA. [Wright, Edwina] Alfred Hosp, Dept Infect Dis, Melbourne, Vic, Australia. [Wright, Edwina] Burnet Inst, Melbourne, Vic, Australia. [Wright, Edwina] Monash Univ, Dept Infect Dis, Melbourne, Vic 3004, Australia. [Dolan, Matthew J.] Mil Med Inc, Henry M Jackson Fdn Adv, Lackland AFB, TX USA. [Ganesan, Anuradha] Walter Reed Natl Mil Med Ctr, Infect Dis Serv, Bethesda, MD USA. [Ferguson, Tomas M.] Tripler Army Med Ctr, Infect Dis Serv, Honolulu, HI 96859 USA. [Smith, Davey M.; Richman, Douglas D.; Little, Susan J.] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Smith, Davey M.; Richman, Douglas D.] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. [Richman, Douglas D.] Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA. [Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. RP Ahuja, SK (reprint author), South Texas Vet Hlth Care Syst, Vet Affairs VA Res Ctr AIDS & HIV Infect 1, 7400 Merton Minter Blvd,Room W200, San Antonio, TX 78229 USA. EM ahujas@uthscsa.edu OI Agan, Brian/0000-0002-5114-1669 FU Veterans Affairs (VA) Research Center [IP1 CX000875-01A1]; National Institutes of Health (NIH) [R37AI046326]; Doris Duke Distinguished Clinical Scientist Award; VA MERIT award; Elizabeth Glaser Pediatric AIDS Foundation; Burroughs Wellcome Clinical Scientist Award; Max and Minnie Tomerlin Voelcker Fund; NIH [UL1TR001120, DA034978, AI43638, AI69432, MH62512, AI74621, MH097520, AI077304, AI007384, AI080193, AI106039, AI096113]; VA Career Development Award-2; National Health and Medical Research Council of Australia; Infectious Disease Clinical Research Program (IDCRP); Uniformed Services University of the Health Sciences [IDCRP-000-03]; National Institute of Allergy and Infectious Diseases; International AIDS Vaccine Initiative [DMS0714991] FX The work was supported by the Veterans Affairs (VA) Research Center for AIDS and HIV Infection and VA Center for Personalized Medicine grant IP1 CX000875-01A1, National Institutes of Health (NIH) MERIT grant R37AI046326, and the Doris Duke Distinguished Clinical Scientist Award to Dr Ahuja. Dr Ahuja is also supported by a VA MERIT award, the Elizabeth Glaser Pediatric AIDS Foundation, the Burroughs Wellcome Clinical Scientist Award in Translational Research and the Senior Scholar Award from the Max and Minnie Tomerlin Voelcker Fund. This work was also supported by NIH grant UL1TR001120 (Clinical and Translational Science Award). Dr Le was supported by a VA Career Development Award-2. DrWright was supported by an Early Career Fellowship from the National Health and Medical Research Council of Australia. Support for this work was also provided in part by the Infectious Disease Clinical Research Program (IDCRP), a Department of Defense program executed through the Uniformed Services University of the Health Sciences (IDCRP-000-03). This project has been funded in part with federal funds from the National Institute of Allergy and Infectious Diseases, NIH, under Inter-Agency Agreement Y1-AI-5072. Drs Smith, Richman, and Little were supported by NIH grants DA034978, AI43638, AI69432, MH62512, AI74621, MH097520, AI077304, AI007384, AI080193, AI106039, and AI096113 and the International AIDS Vaccine Initiative grant DMS0714991. NR 34 TC 24 Z9 24 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JAN PY 2015 VL 175 IS 1 BP 88 EP 99 DI 10.1001/jamainternmed.2014.4010 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA AY1BM UT WOS:000347328500019 PM 25419650 ER PT J AU Japuntich, SJ Eilers, MA Shenhav, S Park, ER Winickoff, JP Benowitz, NL Rigotti, NA AF Japuntich, Sandra J. Eilers, Michelle A. Shenhav, Sharon Park, Elyse R. Winickoff, Jonathan P. Benowitz, Neal L. Rigotti, Nancy A. TI Secondhand Tobacco Smoke Exposure Among Hospitalized Nonsmokers With Coronary Heart Disease SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Japuntich, Sandra J.] Vet Affairs Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Boston, MA USA. [Eilers, Michelle A.; Park, Elyse R.; Winickoff, Jonathan P.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Dept Med, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Shenhav, Sharon] Univ Calif Irvine, Dept Psychol & Social Behav, Irvine, CA USA. [Benowitz, Neal L.] San Francisco Gen Hosp, Dept Med, Div Clin Pharmacol, San Francisco, CA 94110 USA. RP Rigotti, NA (reprint author), Massachusetts Gen Hosp, Dept Med, Tobacco Res & Treatment Ctr, 50 Staniford St,Ninth Floor, Boston, MA 02114 USA. EM nrigotti@partners.org NR 5 TC 4 Z9 4 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JAN PY 2015 VL 175 IS 1 BP 133 EP 136 DI 10.1001/jamainternmed.2014.5476 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA AY1BM UT WOS:000347328500029 PM 25383761 ER PT J AU Corapi, KM McMahon, G Wenger, JB Seifter, JL Bhan, I AF Corapi, Kristin M. McMahon, GearoidM. Wenger, Julia B. Seifter, Julian L. Bhan, Ishir TI Association of Loop Diuretic Use With Higher Parathyroid Hormone Levels in Patients With Normal Renal Function SO JAMA INTERNAL MEDICINE LA English DT Letter ID HYPERPARATHYROIDISM; INSUFFICIENCY C1 [Corapi, Kristin M.; Wenger, Julia B.; Bhan, Ishir] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [McMahon, GearoidM.; Seifter, Julian L.] Brigham & Womens Hosp, Div Nephrol, Boston, MA 02115 USA. RP Corapi, KM (reprint author), Massachusetts Gen Hosp, Div Nephrol, 165 Cambridge St,Ste 302, Boston, MA 02114 USA. EM kcorapi@partners.org OI McMahon, Gearoid/0000-0002-7723-2198 FU NIDDK NIH HHS [T32DK007540, T32 DK007540] NR 6 TC 4 Z9 4 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JAN PY 2015 VL 175 IS 1 BP 137 EP 138 DI 10.1001/jamainternmed.2014.5857 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AY1BM UT WOS:000347328500031 PM 25419564 ER PT J AU Hasegawa, K Sullivan, AF Tsugawa, Y Turner, SJ Massaro, S Clark, S Tsai, CL Camargo, CA AF Hasegawa, Kohei Sullivan, Ashley F. Tsugawa, Yusuke Turner, Stuart J. Massaro, Susan Clark, Sunday Tsai, Chu-Lin Camargo, Carlos A., Jr. CA MARC-36 Investigators TI Comparison of US emergency department acute asthma care quality: 1997-2001 and 2011-2012 SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Acute asthma; emergency department; guideline; concordance; quality of care; hospitalization; regional variation; time trend ID OF-CARE; OUTCOMES; ADULTS; EXACERBATION; PERFORMANCE; INDICATORS; HOSPITALS; CHILDREN; VISITS; TRENDS AB Background: It remains unclear whether the quality of acute asthma care in US emergency departments (EDs) has improved over time. Objectives: We investigated changes in concordance of ED asthma care with 2007 National Institutes of Health guidelines, identified ED characteristics predictive of concordance, and tested whether higher concordance was associated with lower risk of hospitalization. Methods: We performed chart reviews in ED patients aged 18 to 54 years with asthma exacerbations in 48 EDs during 2 time periods: 1997-2001 (2 prior studies) and2011-2012 (new study). Concordance with guideline recommendations was evaluated by using item-by-item quality measures and composite concordance scores at the patient and ED levels; these scores ranged from 0 to 100. Results: The analytic cohort comprised 4039 patients (2119 from 1997-2001 vs 1920 from 2011-2012). Over these 16 years, emergency asthma care became more concordant with level A recommendations at both the patient and ED levels (both P<.001). By contrast, concordance with non-level A recommendations (peak expiratory flow measurement and timeliness) decreased at both the patient (median score, 75 [interquartile range, 50-100] to 50 [interquartile range, 33-75], P<.001) and ED (mean score, 67 [SD, 7] to 50 [SD, 16], P<.001) levels. Multivariable analysis demonstrated ED concordance was lower in Southern and Western EDs compared with Midwestern EDs. After adjusting for severity, guideline-concordant care was associated with lower risk of hospitalization (odds ratio, 0.37; 95% CI, 0.26-0.53). Conclusions: Between 1997 and 2012, we observed changes in the quality of emergency asthma care that differed by level of guideline recommendation and substantial interhospital and geographic variations. Greater concordance with guideline-recommended management might reduce unnecessary hospitalizations. C1 [Hasegawa, Kohei; Sullivan, Ashley F.; Tsai, Chu-Lin; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Tsugawa, Yusuke] Harvard Interfac Initiat Hlth Policy, Cambridge, England. [Turner, Stuart J.; Massaro, Susan] Novartis Pharmaceut, E Hanover, NJ USA. [Clark, Sunday] Weill Cornell Med Coll, Dept Emergency Med, New York, NY USA. RP Hasegawa, K (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Suite 410,326 Cambridge St, Boston, MA 02114 USA. EM khasegawa1@partners.org RI Shapiro, Nathan/F-1718-2016; OI Pallin, Daniel/0000-0002-8517-9702; TSAI, CHU-LIN/0000-0003-4639-1513 FU Novartis Pharmaceuticals Corporation FX Supported by a grant from Novartis Pharmaceuticals Corporation to Massachusetts General Hospital (principal investigator: Camargo). The sponsor had no role in the conduct of the study, nor collection, management, or analysis of the data. NR 37 TC 4 Z9 4 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2015 VL 135 IS 1 BP 73 EP U522 DI 10.1016/j.jaci.2014.08.028 PG 15 WC Allergy; Immunology SC Allergy; Immunology GA AY0PG UT WOS:000347298200009 PM 25263233 ER PT J AU Charbonnier, LM Janssen, E Chou, J Ohsumi, TK Keles, S Hsu, JT Massaad, MJ Garcia-Lloret, M Hanna-Wakim, R Dbaibo, G Alangari, AA Alsultan, A Al-Zahrani, D Geha, RS Chatila, TA AF Charbonnier, Louis-Marie Janssen, Erin Chou, Janet Ohsumi, Toshiro K. Keles, Sevgi Hsu, Joyce T. Massaad, Michel J. Garcia-Lloret, Maria Hanna-Wakim, Rima Dbaibo, Ghassan Alangari, Abdullah A. Alsultan, Abdulrahman Al-Zahrani, Daifulah Geha, Raif S. Chatila, Talal A. TI Regulatory T-cell deficiency and immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like disorder caused by loss-of-function mutations in LRBA SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Autoantibodies; autoimmunity; forkhead box P3; immune dysregulation; polyendocrinopathy; enteropathy; X-linked syndrome; LPS-responsive beige-like anchor; mammalian target of rapamycin complex; T follicular helper cells; T follicular regulatory cells; regulatory T cells ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; FOXP3; AUTOIMMUNITY; EXPRESSION; DISEASE; PROTEIN; GENE; DIFFERENTIATION; ACCUMULATION; MECHANISMS AB Background: A number of heritable immune dysregulatory diseases result from defects affecting regulatory T (Treg) cell development, function, or both. They include immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, which is caused by mutations in forkhead box P3 (FOXP3), and IPEX-like disorders caused by mutations in IL-2 receptor a (IL2RA), signal transducer and activator of transcription 5b (STAT5b), and signal transducer and activator of transcription 1 (STAT1). However, the genetic defects underlying many cases of IPEX-like disorders remain unknown. Objective: We sought to identify the genetic abnormalities in patients with idiopathic IPEX-like disorders. Methods: We performed whole-exome and targeted gene sequencing and phenotypic and functional analyses of Treg cells. Results: A child who presented with an IPEX-like syndrome and severe Treg cell deficiency was found to harbor a nonsense mutation in the gene encoding LPS-responsive beige-like anchor (LRBA), which was previously implicated as a cause of common variable immunodeficiency with autoimmunity. Analysis of subjects with LRBA deficiency revealed marked Treg cell depletion; profoundly decreased expression of canonical Treg cell markers, including FOXP3, CD25, Helios, and cytotoxic T lymphocyte-associated antigen 4; and impaired Treg cellmediated suppression. There was skewing in favor of memory T cells and intense autoantibody production, with marked expansion of T follicular helper and contraction of T follicular regulatory cells. Whereas the frequency of recent thymic emigrants and the differentiation of induced Treg cells were normal, LRBA-deficient T cells exhibited increased apoptosis and reduced activities of the metabolic sensors mammalian target of rapamycin complexes 1 and 2. Conclusion: LRBA deficiency is a novel cause of IPEX-like syndrome and Treg cell deficiency associated with metabolic dysfunction and increased apoptosis of Treg cells. C1 [Charbonnier, Louis-Marie; Janssen, Erin; Chou, Janet; Keles, Sevgi; Hsu, Joyce T.; Massaad, Michel J.; Geha, Raif S.; Chatila, Talal A.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Immunol, Boston, MA USA. [Charbonnier, Louis-Marie; Janssen, Erin; Chou, Janet; Keles, Sevgi; Hsu, Joyce T.; Massaad, Michel J.; Geha, Raif S.; Chatila, Talal A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Ohsumi, Toshiro K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Garcia-Lloret, Maria] Univ Calif Los Angeles, Dept Pediat, Div Immunol, Los Angeles, CA 90024 USA. [Hanna-Wakim, Rima; Dbaibo, Ghassan] Amer Univ Beirut, Div Pediat Infect Dis, Beirut, Lebanon. [Alangari, Abdullah A.; Alsultan, Abdulrahman] King Saud Univ, Coll Med, Dept Pediat, Riyadh 11461, Saudi Arabia. [Al-Zahrani, Daifulah] King Abdul Aziz Med City, Immunol & Allergy Pediat Dept, Jeddah, Saudi Arabia. RP Chatila, TA (reprint author), Boston Childrens Hosp, Div Immunol, One Blackfan Circle, Boston, MA 02115 USA. EM talal.chatila@childrens.harvard.edu FU National Institutes of Health (NIH) [R01AI085090, 1R01AI100315]; Children's Health Research Centers Career Development Awards [5K12HD052896, 1K12HD052896-01A1]; Jeffrey Modell Foundation Translational Research Program Grant Award; Dubai-Harvard Foundation for Medical Research; Jeffrey Model Foundation; Scientific and Technological Research Council of Turkey [059B191300622] FX Supported by National Institutes of Health (NIH) grants R01AI085090 (to T. A.C.) and 1R01AI100315 (to R.S.G), Children's Health Research Centers Career Development Awards 5K12HD052896 and 1K12HD052896-01A1 (to E.J and J.C., respectively), a Jeffrey Modell Foundation Translational Research Program Grant Award (to J.C.), grants from the Dubai-Harvard Foundation for Medical Research and the Jeffrey Model Foundation (to R. S.G.) and a Scientific and Technological Research Council of Turkey grant 059B191300622 (to S.K.). NR 43 TC 39 Z9 44 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2015 VL 135 IS 1 BP 217 EP U336 DI 10.1016/j.jaci.2014.10.019 PG 20 WC Allergy; Immunology SC Allergy; Immunology GA AY0PG UT WOS:000347298200026 PM 25468195 ER PT J AU Walter, JE Lo, MS Kis-Toth, K Tirosh, I Frugoni, F Lee, YN Csomos, K Chen, K Pillai, S Dunham, J Tsokos, GC Prak, ETL Notarangelo, LD AF Walter, Jolan E. Lo, Mindy S. Kis-Toth, Katalin Tirosh, Irit Frugoni, Francesco Lee, Yu Nee Csomos, Krisztian Chen, Karin Pillai, Shiv Dunham, Jonathan Tsokos, George C. Prak, Eline T. Luning Notarangelo, Luigi D. TI Impaired receptor editing and heterozygous RAG2 mutation in a patient with systemic lupus erythematosus and erosive arthritis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID OMENN-SYNDROME; IMMUNODEFICIENCY; DEFECTS; DISEASE; CELLS C1 [Walter, Jolan E.; Lo, Mindy S.; Tirosh, Irit; Frugoni, Francesco; Lee, Yu Nee; Notarangelo, Luigi D.] Boston Childrens Hosp, Div Immunol, Boston, MA 02115 USA. [Walter, Jolan E.; Csomos, Krisztian] Massachusetts Gen Hosp Children, Div Pediat Allergy Immunol, Boston, MA USA. [Kis-Toth, Katalin] Beth Israel Deaconess Med Ctr, Div Rheumatol, Boston, MA 02215 USA. [Chen, Karin] Univ Utah, Sch Med, Dept Pediat, Div Rheumatol Allergy & Immunol, Salt Lake City, UT USA. [Pillai, Shiv] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Dunham, Jonathan] Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA. [Prak, Eline T. Luning] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Notarangelo, Luigi D.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA USA. [Notarangelo, Luigi D.] Harvard Stem Cell Inst, Boston, MA USA. RP Walter, JE (reprint author), Boston Childrens Hosp, Div Immunol, Boston, MA 02115 USA. EM jewalter@partners.org RI Notarangelo, Luigi/F-9718-2016; OI Notarangelo, Luigi/0000-0002-8335-0262; Frugoni, Francesco/0000-0002-1769-8121 FU NIAID NIH HHS [P01 AI076210, 5K08AI103035, 5P01AI076210-04, K08 AI103035, R01 AI042269, R01 AI42269, U54 AI082973, U54AI082973]; NIDDK NIH HHS [P30 DK040561] NR 11 TC 3 Z9 3 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2015 VL 135 IS 1 BP 272 EP 273 DI 10.1016/j.jaci.2014.07.063 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA AY0PG UT WOS:000347298200036 PM 25312763 ER PT J AU Long, A Rothman, K Chen, H Carrigan, G Szefler, S AF Long, Aidan Rothman, Kenneth Chen, Hubert Carrigan, Gillis Szefler, Stanley CA EXCELS Study Authors TI EXCELS study results do not rule out potential cancer risk with omalizumab Reply SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter C1 [Long, Aidan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Clin Immunol, Boston, MA 02114 USA. [Rothman, Kenneth] RTI Hlth Solut, Res Triangle Pk, NC USA. [Chen, Hubert; Carrigan, Gillis] Genentech Inc, San Francisco, CA 94080 USA. [Szefler, Stanley] Childrens Hosp Colorado, Denver, CO USA. [Szefler, Stanley] Univ Colorado, Sch Med, Denver, CO USA. RP Long, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Clin Immunol, Boston, MA 02114 USA. EM AALONG@mgh.harvard.edu NR 2 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2015 VL 135 IS 1 BP 289 EP 290 DI 10.1016/j.jaci.2014.09.018 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA AY0PG UT WOS:000347298200045 PM 25441293 ER PT J AU Hamilton, AB Chinman, M Cohen, AN Oberman, RS Young, AS AF Hamilton, Alison B. Chinman, Matthew Cohen, Amy N. Oberman, Rebecca Shoai Young, Alexander S. TI Implementation of Consumer Providers into Mental Health Intensive Case Management Teams SO JOURNAL OF BEHAVIORAL HEALTH SERVICES & RESEARCH LA English DT Article ID PEER SUPPORT; CONCEPTUAL-FRAMEWORK; STRATEGIES; PROGRAMS; FACILITATION; EXPERIENCES; AGENCIES; SERVICES; STAFF; VA AB In mental health care, consumer providers (CPs) are individuals with serious mental illness (SMI) who draw upon their lived experiences while providing services to others with SMI. Implementation of CPs has proven to be challenging in a variety of settings. The PEER project (Peers Enhancing Recovery) involved rolling out CPs using an implementation science model and evaluating implementation and impact in mental health treatment settings (three intervention, three control). In qualitative interviews, facilitators and challenges to implementation were described by the CPs, their team members, clients, and study researchers. Site preparation, external facilitation, and positive, reinforcing experiences with CPs facilitated implementation. Role definitions and deficiencies in CPs' technical knowledge posed challenges to implementation. Sustainability was not realized due to insufficient resources. However, implementation was positive overall, characterized by diffusion of innovation concepts of high relative advantage, strong trialability, compatibility with prevailing norms, compelling observability, and relatively low complexity. By preparing and working systematically with intervention sites to incorporate new services, implementation was strengthened and challenges were minimized. C1 [Hamilton, Alison B.; Cohen, Amy N.; Oberman, Rebecca Shoai; Young, Alexander S.] VA Greater Los Angeles Healthcare Syst, VA Desert Pacific MIRECC, Los Angeles, CA 90073 USA. [Chinman, Matthew] VA Pittsburgh Healthcare Syst, VISN MIRECC 4, Pittsburgh, PA USA. RP Hamilton, AB (reprint author), VA Greater Los Angeles Healthcare Syst, VA Desert Pacific MIRECC, 11301 Wilshire Blvd 210A, Los Angeles, CA 90073 USA. EM alisonh@ucla.edu; chinman@rand.org; amy.cohen@va.gov; rebecca.oberman@va.gov; ayoung@ucla.edu FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [IIR 06-227]; Mental Illness Research, Education, and Clinical Center of VISN 4; Mental Illness Research, Education, and Clinical Center of VISN 22; National Institute of Mental Health [R25 MH080916-01A2]; VA HSRD QUERI FX The research reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (IIR 06-227). Support was also provided by the Mental Illness Research, Education, and Clinical Centers of VISN 4 and VISN 22. At the time of the study, Dr. Hamilton was an investigator with the Implementation Research Institute (IRI), at the George Warren Brown School of Social Work, Washington University, St. Louis, through an award from the National Institute of Mental Health (R25 MH080916-01A2) and VA HSR&D QUERI. NR 20 TC 5 Z9 5 U1 2 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1094-3412 EI 1556-3308 J9 J BEHAV HEALTH SER R JI J. Behav. Health Serv. Res. PD JAN PY 2015 VL 42 IS 1 BP 100 EP 108 DI 10.1007/s11414-013-9365-8 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AY2KW UT WOS:000347420100010 PM 24091610 ER PT J AU Chinman, M Oberman, RS Hanusa, BH Cohen, AN Salyers, MP Twamley, EW Young, AS AF Chinman, Matthew Oberman, Rebecca S. Hanusa, Barbara H. Cohen, Amy N. Salyers, Michelle P. Twamley, Elizabeth W. Young, Alexander S. TI A Cluster Randomized Trial of Adding Peer Specialists to Intensive Case Management Teams in the Veterans Health Administration SO JOURNAL OF BEHAVIORAL HEALTH SERVICES & RESEARCH LA English DT Article ID ASSERTIVE COMMUNITY TREATMENT; PATIENT ACTIVATION MEASURE; SERIOUS MENTAL-ILLNESS; CONSUMER-PROVIDERS; SELF-MANAGEMENT; CLIENT OUTCOMES; RECOVERY; PROGRAM; SERVICES; SUPPORT AB Use of peer specialists (PSs)-individuals with serious mental illness who use their experiences to help others with serious mental illness-is increasing. However, their impact on patient outcomes has not been demonstrated definitively. This cluster randomized, controlled trial within the Veterans Health Administration compared patients served by three intensive case management teams that each deployed two PSs for 1 year, to the patients of three similar teams without PSs (Usual Care). All patients (PS group = 149, Usual Care = 133) had substantial psychiatric inpatient histories and a primary Axis 1 psychiatric disorder. Before and after the year PSs worked, patients were surveyed on their recovery, quality of life, activation (health self-management efficacy), interpersonal relations, and symptoms. Patients in the PS group improved significantly more (z = 2.00, df = 1, p = 0.05) than those receiving Usual Care on activation. There were no other significant differences. PSs helped patients become more active in treatment, which can promote recovery. C1 [Chinman, Matthew] VA Pittsburgh Healthcare, VISN 4, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA 15240 USA. [Chinman, Matthew] RAND Corp, VA Healthcare Syst, Pittsburgh, PA 15206 USA. [Oberman, Rebecca S.] West Los Angeles VA Healthcare Syst, VA Desert Pacific Mental Illness Res Educ & Clin, MIRECC, Los Angeles, CA 90073 USA. [Hanusa, Barbara H.] VA Pittsburgh Healthcare, Ctr Hlth Equ Res & Promot CHERP, Pittsburgh, PA 15206 USA. [Hanusa, Barbara H.] VA Pittsburgh Healthcare, MIRECC, Pittsburgh, PA 15206 USA. [Cohen, Amy N.] VA Desert Pacific Mental Illness Res Educ & Clin, Hlth Serv Unit, Los Angeles, CA USA. [Cohen, Amy N.] Univ Calif Los Angeles, MIRECC, West Los Angeles VA Healthcare Syst, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90073 USA. [Salyers, Michelle P.] Indiana Univ Purdue Univ, IUPUI Sch Sci LD, Dept Psychol, Indianapolis, IN 46202 USA. [Twamley, Elizabeth W.] VA San Diego Healthcare Syst, Ctr Excellence, Neuropsychol Unit, San Diego, CA USA. [Twamley, Elizabeth W.] Univ Calif San Diego, San Diego, CA 92103 USA. RP Chinman, M (reprint author), VA Pittsburgh Healthcare, VISN 4, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA 15240 USA. EM matthew_chinman@rand.org; Rebecca.Shoai@va.gov; barbara.hanusa@va.gov; Amy.cohen@va.gov; mpsalyer@iupui.edu; etwamley@ucsd.edu; Ayoung@ucla.edu RI Young, Alexander/A-1523-2009 OI Young, Alexander/0000-0002-9367-9213 FU Department of Veterans' Affairs Health Services Research and Development, PEers Enhancing Recovery (PEER) [IIR 06-227] FX Financial support for the paper was provided by a grant from the Department of Veterans' Affairs Health Services Research and Development, PEers Enhancing Recovery (PEER, IIR 06-227). All authors do not have any conflict of interests to report. The contents do not represent the views of the Department of Veterans Affairs or the US Government. Dr. Chinman had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. NR 71 TC 11 Z9 11 U1 3 U2 20 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1094-3412 EI 1556-3308 J9 J BEHAV HEALTH SER R JI J. Behav. Health Serv. Res. PD JAN PY 2015 VL 42 IS 1 BP 109 EP 121 DI 10.1007/s11414-013-9343-1 PG 13 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AY2KW UT WOS:000347420100011 PM 23657754 ER PT J AU Chinman, M Oberman, RS Hanusa, BH Cohen, AN Salyers, MP Twamley, EW Young, AS AF Chinman, Matthew Oberman, Rebecca S. Hanusa, Barbara H. Cohen, Amy N. Salyers, Michelle P. Twamley, Elizabeth W. Young, Alexander S. TI A Cluster Randomized Trial of Adding Peer Specialists to Intensive Case Management Teams in the Veterans Health Administration (vol 42, pg 109, 2015) SO JOURNAL OF BEHAVIORAL HEALTH SERVICES & RESEARCH LA English DT Correction C1 [Chinman, Matthew] VA Pittsburgh Healthcare, Mental Illness Res Educ & Clin Ctr, VISN 4, Pittsburgh, PA 15240 USA. [Chinman, Matthew] RAND Corp, VA Healthcare Syst, Pittsburgh, PA 15206 USA. RP Chinman, M (reprint author), VA Pittsburgh Healthcare, Mental Illness Res Educ & Clin Ctr, VISN 4, Pittsburgh, PA 15240 USA. EM matthew_chinman@rand.org NR 1 TC 0 Z9 0 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1094-3412 EI 1556-3308 J9 J BEHAV HEALTH SER R JI J. Behav. Health Serv. Res. PD JAN PY 2015 VL 42 IS 1 BP 122 EP 122 DI 10.1007/s11414-013-9377-4 PG 1 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AY2KW UT WOS:000347420100012 PM 24217992 ER PT J AU Ezura, Y Nagata, J Nagao, M Hemmi, H Hayata, T Rittling, S Denhardt, DT Noda, M AF Ezura, Yoichi Nagata, Junji Nagao, Masashi Hemmi, Hiroaki Hayata, Tadayoshi Rittling, Susan Denhardt, David T. Noda, Masaki TI Hindlimb-unloading suppresses B cell population in the bone marrow and peripheral circulation associated with OPN expression in circulating blood cells SO JOURNAL OF BONE AND MINERAL METABOLISM LA English DT Article DE Osteopontin; Tail-suspension; Hindlimb unloading; PBMC; Lymphocyte fraction ID SYMPATHETIC-NERVOUS-SYSTEM; STEM-CELLS; OSTEOPONTIN; STRESS; MECHANISMS; RESORPTION; ANTIBODY; ATROPHY; THYMUS; GENE AB Rodent hindlimb unloading (HU) by tail-suspension is a model to investigate disuse-induced bone loss in vivo. Previously, we have shown that osteopontin (OPN, also known as Spp1) is required for unloading-induced bone loss. However, how unloading affects OPN expression in the body is not fully understood. Here, we examined OPN expression in peripheral blood of mice subjected to HU. Real-time RT-PCR analysis indicated that OPN expression is increased in circulating peripheral blood cells. This HU-induced increase in OPN mRNA expression was specific in circulating peripheral blood cells, as OPN was not increased in the blood cells in bone marrow. HU-induced enhancement in OPN expression in peripheral blood cells was associated with an increase in the fraction of monocyte/macrophage lineage cells in the peripheral blood. In contrast, HU decreased the fraction size of B-lymphocytes in the peripheral blood. We further examined if B-lymphogenesis is affected in the mice deficient for osteopontin subjected to HU. In bone marrow, HU decreased the population of the B-lymphocyte lineage cells significantly, whereas it did not alter the population of monocyte/macrophage lineage cells. HU also increased the cells in T-lymphocyte lineage in bone marrow. Interestingly, these changes were observed similarly both in OPN-deficient and wild-type mice. These results indicate for the first time that HU increases OPN expression in circulating cells and suppresses bone marrow B-lymphogenesis. C1 [Ezura, Yoichi; Nagata, Junji; Nagao, Masashi; Hemmi, Hiroaki; Hayata, Tadayoshi; Noda, Masaki] Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Pharmacol, Bunkyo Ku, Tokyo 1138510, Japan. [Ezura, Yoichi; Noda, Masaki] TMDU, Hard Tissue Genome Res Ctr, Tokyo, Japan. [Hemmi, Hiroaki] TMDU, Med Top Track Fellow Program MTT, Tokyo, Japan. [Rittling, Susan] Forsyth Inst, Boston, MA 02115 USA. [Denhardt, David T.] Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ 08854 USA. [Noda, Masaki] Int Res Ctr Mol Sci Tooth & Bone Dis, Global Ctr Excellence GCOE Program, Tokyo, Japan. [Noda, Masaki] JSPS Core Core Program, Integrated Act Initiat, Tokyo, Japan. RP Ezura, Y (reprint author), Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Pharmacol, Bunkyo Ku, 5-45 Yushima 1 Chome, Tokyo 1138510, Japan. EM ezura.mph@mri.tmd.ac.jp RI Ezura, Yoichi/L-9485-2016 FU Japanese Ministry of Education, Global Center of Excellence (GCOE) Program, "International Research Center for Molecular Science in Tooth and Bone Diseases"; Japan Space forum, NASDA, Japan Society for Promotion of Science (JSPS Core to Core Program, "Research for the Future Program"); Japan Science and Technology Agency (JST) [3K019] FX This work was supported by a grant from the Japanese Ministry of Education, Global Center of Excellence (GCOE) Program, "International Research Center for Molecular Science in Tooth and Bone Diseases", and grants from the Japan Space forum, NASDA, Japan Society for Promotion of Science (JSPS Core to Core Program, "Research for the Future Program"), and Japan Science and Technology Agency (JST) 3K019. NR 19 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER JAPAN KK PI TOKYO PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065, JAPAN SN 0914-8779 EI 1435-5604 J9 J BONE MINER METAB JI J. Bone Miner. Metab. PD JAN PY 2015 VL 33 IS 1 BP 48 EP 54 DI 10.1007/s00774-014-0568-8 PG 7 WC Endocrinology & Metabolism; Medicine, Research & Experimental SC Endocrinology & Metabolism; Research & Experimental Medicine GA AY2GX UT WOS:000347407900007 PM 24831120 ER PT J AU Lynch, CP Gebregziabher, M Axon, RN Hunt, KE Payne, E Egede, LE AF Lynch, Cheryl P. Gebregziabher, Mulugeta Axon, R. Neal Hunt, Kelly E. Payne, Elizabeth Egede, Leonard E. TI Geographic and Racial/Ethnic Variations in Patterns of Multimorbidity Burden in Patients with Type 2 Diabetes SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE multimorbidity; racial/ethnic; rural residence; pattern; veterans ID MEDICATION NONADHERENCE; GENERAL-PRACTICE; HEALTH-STATUS; VETERANS; PREVALENCE; CARE; MANAGEMENT; MORTALITY; DISEASES; PROGRAM AB Multimorbidity presents a significant public health challenge, but regional, rural/urban, and racial/ethnic differences in patterns of multimorbidity in diabetes are poorly understood. To describe patterns of multimorbidity in medical and mental health by regional, rural/urban, and racial/ethnic variation in patients with type 2 diabetes mellitus. Retrospective cohort study from 2002 through 2006 A national cohort of 892,223 veterans with diabetes Multimorbidity was the main outcome defined as: the measure of multimorbidity and two categorical outcomes, with pattern of medical and mental health comorbidities combined and separately. Among patients, 52% had 2+ comorbidities, 33% had a single comorbidity, and 14% had no comorbidity; 13.9% had both medical and mental health comorbidities, 70.3% had medical only, and 1.5% had mental health only. The odds of having 3+ comorbidities were nearly fourfold greater in patients 75 years and older relative to patients younger than 50 years (OR=3.95 [95% CI: 3.84, 4.06]). Compared to non-Hispanic whites, the odds of 3+ comorbidities among non-Hispanic blacks were 1.67 times greater (95% CI: 1.63, 1.71). Hispanics were more likely to have a mental health comorbidity alone (OR=1.20 [95% CI: 1.13, 1.28]) than non-Hispanic whites. For patients living in rural areas, the odds were higher of having 3+ comorbidities (OR=1.21 [95% CI: 1.19, 1.23]) and of having both medical and mental health comorbidities (OR=1.15 [95% CI: 1.13, 1.17]) compared to urban dwellers. Among individuals with diabetes, traditionally disadvantaged groups, including non-Hispanic blacks and rural patients, appear to bear the greatest burden and risk of multimorbidity. Significantly greater odds with increasing number of comorbidities were seen by race/ethnicity, rural residence, and geographic region. C1 [Lynch, Cheryl P.; Gebregziabher, Mulugeta; Axon, R. Neal; Hunt, Kelly E.; Payne, Elizabeth; Egede, Leonard E.] Ralph H Johnson Dept Vet Affairs Med Ctr, Hlth Equ & Rural Outreach Innovat Ctr, Charleston, SC USA. [Lynch, Cheryl P.; Axon, R. Neal; Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Gebregziabher, Mulugeta; Hunt, Kelly E.; Payne, Elizabeth] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Div Gen Internal Med, Ctr Hlth Dispar Res, 135 Rutledge Ave,MSC 593, Charleston, SC 29425 USA. EM egedel@musc.edu OI Gebregziabher, Mulugeta/0000-0002-4826-481X FU NIDDK NIH HHS [K24 DK093699] NR 38 TC 6 Z9 6 U1 3 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2015 VL 30 IS 1 BP 25 EP 32 DI 10.1007/s11606-014-2990-y PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AY2JG UT WOS:000347414800007 PM 25127728 ER PT J AU Adepoju, O AF Adepoju, Omolola TI Capsule Commentary on Lynch et al., Geographic and Racial/Ethnic Variations in Patterns of Multimorbidity Burden in Patients with Type 2 Diabetes SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material C1 [Adepoju, Omolola] United Hlth Grp, Accountable Care Program, Sugar Land, TX USA. [Adepoju, Omolola] United Hlth Grp, Hlth Homes Program, Sugar Land, TX USA. RP Adepoju, O (reprint author), Baylor Coll Med, Sect Hlth Serv Res Vet Affairs Hlth Serv Res & De, Michael E DeBakey Vet Affairs Med Ctr, Ctr Innovat Qual Effectiveness & Safety, Houston, TX 77030 USA. EM omololaelizabeth.adepoju@va.gov NR 5 TC 1 Z9 1 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2015 VL 30 IS 1 BP 93 EP 93 DI 10.1007/s11606-014-3005-8 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AY2JG UT WOS:000347414800017 PM 25361684 ER PT J AU Agrawal, MD Thimmappa, ND Vasile, JV Levine, JL Allen, RJ Greenspun, DT Ahn, CY Chen, CM Hedgire, SS Prince, MR AF Agrawal, Mukta D. Thimmappa, Nanda Deepa Vasile, Julie V. Levine, Joshua L. Allen, Robert J. Greenspun, David T. Ahn, Christina Y. Chen, Constance M. Hedgire, Sandeep S. Prince, Martin R. TI Autologous Breast Reconstruction: Preoperative Magnetic Resonance Angiography for Perforator Flap Vessel Mapping SO JOURNAL OF RECONSTRUCTIVE MICROSURGERY LA English DT Article DE MRA; blood pool contrast agent; perforator flap artery imaging ID ABDOMINAL-WALL; GRACILIS MUSCLE; MR-ANGIOGRAPHY; VENOUS ANATOMY; CT ANGIOGRAPHY; SUPERIOR AB BackgroundSelection of a vascular pedicle for autologous breast reconstruction is time consuming and depends on visual evaluation during the surgery. Preoperative imaging of donor site for mapping the perforator artery anatomy greatly improves the efficiency of perforator selection and significantly reduces the operative time. In this article, we present our experience with magnetic resonance angiography (MRA) for perforator vessel mapping including MRA technique and interpretation. MethodsWe have performed over 400 MRA examinations from August 2008 to August 2013 at our institution for preoperative imaging of donor site for mapping the perforator vessel anatomy. Using our optimized imaging protocol with blood pool magnetic resonance imaging contrast agents, multiple donor sites can be imaged in a single MRA examination. Following imaging using the postprocessing and reporting tool, we estimated incidence of commonly used perforators for autologous breast reconstruction. ResultsIn our practice, anterior abdominal wall tissue is the most commonly used donor site for perforator flap breast reconstruction and deep inferior epigastric artery perforators are the most commonly used vascular pedicle. A thigh flap, based on the profunda femoral artery perforator has become the second most used flap at our institution. In addition, MRA imaging also showed evidence of metastatic disease in 4% of our patient subset. ConclusionOur MRA technique allows the surgeons to confidently assess multiple donor sites for the best perforator and flap design. In conclusion, a well-performed MRA with specific postprocessing provides an accurate method for mapping perforator vessel, at the same time avoiding ionizing radiation. C1 [Agrawal, Mukta D.; Hedgire, Sandeep S.] Massachusetts Gen Hosp Imaging, Dept Radiol, Arlington, MA 02476 USA. [Thimmappa, Nanda Deepa; Prince, Martin R.] Weill Cornell Imaging NewYork Presbyterian Hosp, Dept Radiol, New York, NY USA. [Vasile, Julie V.; Levine, Joshua L.; Allen, Robert J.; Greenspun, David T.] New York Eye & Ear Infirm, Dept Microsurg, New York, NY 10003 USA. [Vasile, Julie V.] Northern Westchester Hosp, Dept Plast Surg, New York, NY USA. [Ahn, Christina Y.] NYU Langone Med Ctr, Dept Plast Surg, New York, NY USA. [Chen, Constance M.] Columbia Univ, NewYork Presbyterian Hosp, New York, NY USA. RP Agrawal, MD (reprint author), Massachusetts Gen Hosp Imaging, Dept Radiol, 846 Massachusetts Ave,Apt 3D, Arlington, MA 02476 USA. EM mukta.dr@gmail.com RI Prince, Martin/S-6850-2016; OI Prince, Martin/0000-0002-9883-0584 NR 31 TC 5 Z9 6 U1 0 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0743-684X EI 1098-8947 J9 J RECONSTR MICROSURG JI J. Reconstr. Microsurg. PD JAN PY 2015 VL 31 IS 1 BP 1 EP 11 DI 10.1055/s-0034-1372475 PG 11 WC Surgery SC Surgery GA AY1TO UT WOS:000347375100001 PM 24875438 ER PT J AU Veillette, M Coutu, M Richard, J Batraville, LA Dagher, O Bernard, N Tremblay, C Kaufmann, DE Roger, M Finzi, A AF Veillette, Maxime Coutu, Mathieu Richard, Jonathan Batraville, Laurie-Anne Dagher, Olina Bernard, Nicole Tremblay, Crcile Kaufmann, Daniel E. Roger, Michel Finzi, Andres TI The HIV-1 gp120 CD4-Bound Conformation Is Preferentially Targeted by Antibody-Dependent Cellular Cytotoxicity-Mediating Antibodies in Sera from HIV-1-Infected Individuals SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; VACCINE EFFICACY TRIAL; DISEASE PROGRESSION; DENDRITIC CELLS; VPU PROTEIN; CD4; ADCC; INFECTION; RECEPTOR; C1 AB Recent studies have linked antibody Fc-mediated effector functions with protection or control of human immunodeficiency type 1 (HIV-1) and simian immunodeficiency (SIV) infections. Interestingly, the presence of antibodies with potent antibody-dependent cellular cytotoxicity (ADCC) activity in the Thai RV144 vaccine trial was suggested to correlate with decreased HIV-1 acquisition risk. These antibodies recently were found to recognize HIV envelope (Env) epitopes exposed upon Env-CD4 interaction. CD4 downregulation by Nef and Vpu, as well as Vpu-mediated BST-2 antagonism, were reported to modulate exposure of those CD4-induced HIV-1 Env epitopes and were proposed to play a role in reducing the susceptibility of infected cells to ADCC mediated by this class of antibodies. Here, we report the high prevalence of antibodies recognizing CD4-induced HIV-1 Env epitopes in sera from HIV-1-infected individuals, which correlated with their ability to mediate ADCC responses against HIV-1-infected cells, exposing these Env epitopes at the cell surface. Furthermore, our results indicate that Env variable regions V1, V2, V3, and V5 do not represent a major determinant for ADCC responses mediated by sera from HIV-1-infected individuals. Altogether, these findings suggest that HIV-1 tightly controls the exposure of certain Env epitopes at the surface of infected cells in order to prevent elimination by Fc-effector functions. IMPORTANCE Here, we identified a particular conformation of HIV-1 Env that is specifically targeted by ADCC-mediating antibodies present in sera from HIV-1-infected individuals. This observation suggests that HIV-1 developed sophisticated mechanisms to minimize the exposure of these epitopes at the surface of infected cells. C1 [Veillette, Maxime; Coutu, Mathieu; Richard, Jonathan; Batraville, Laurie-Anne; Dagher, Olina; Tremblay, Crcile; Kaufmann, Daniel E.; Roger, Michel; Finzi, Andres] Univ Montreal, Ctr Rech, CHUM, Montreal, PQ, Canada. [Veillette, Maxime; Coutu, Mathieu; Richard, Jonathan; Batraville, Laurie-Anne; Tremblay, Crcile; Kaufmann, Daniel E.; Roger, Michel; Finzi, Andres] Univ Montreal, Dept Microbiol Infectiol & Immunol, Montreal, PQ, Canada. [Bernard, Nicole] McGill Univ, Dept Expt Med, Montreal, PQ, Canada. [Kaufmann, Daniel E.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA USA. [Finzi, Andres] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ, Canada. RP Finzi, A (reprint author), Univ Montreal, Ctr Rech, CHUM, Montreal, PQ, Canada. EM andres.finzi@umontreal.ca FU Canada Foundation for Innovation; CIHR [119334, 134117, 126630, 291485, 135349]; FRQS [26702]; FRQS AIDS and Infectious Diseases Network FX This work was supported by a Canada Foundation for Innovation Program Leader grant, by CIHR operating grants 119334 and 134117, by FRQS Establishment of Young Scientist grant 26702 to A.F., by CIHR catalyst grant 126630 to A.F. and M.R., and by the FRQS AIDS and Infectious Diseases Network. A.F. is the recipient of a Canada Research Chair on Retroviral Entry. M.V. was supported by CIHR doctoral research award 291485, and J.R. is the recipient of CIHR fellowship award 135349. NR 45 TC 34 Z9 34 U1 0 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD JAN PY 2015 VL 89 IS 1 BP 545 EP 551 DI 10.1128/JVI.02868-14 PG 7 WC Virology SC Virology GA AX8RL UT WOS:000347176100046 PM 25339767 ER PT J AU Berrios, C Jung, J Primi, B Wang, M Pedamallu, C Duke, F Marcelus, C Cheng, JW Garcea, RL Meyerson, M DeCaprio, JA AF Berrios, Christian Jung, Joonil Primi, Blake Wang, Michael Pedamallu, Chandrasekhar Duke, Fujiko Marcelus, Christina Cheng, Jingwei Garcea, Robert L. Meyerson, Matthew DeCaprio, James A. CA TEDDY Study Grp TI Malawi Polyomavirus Is a Prevalent Human Virus That Interacts with Known Tumor Suppressors SO JOURNAL OF VIROLOGY LA English DT Article ID MERKEL CELL POLYOMAVIRUS; SMALL-T-ANTIGEN; AFRICAN-GREEN MONKEY; PROTEIN PHOSPHATASE-2A; GENOME; IDENTIFICATION; TRANSFORMATION; COMPLEXES; DISEASE; P53 AB Malawi polyomavirus (MWPyV) is a recently identified human polyomavirus. Serology for MWPyV VP1 indicates that infection frequently occurs in childhood and reaches a prevalence of 75% in adults. The MWPyV small T antigen (ST) binds protein phosphatase 2A (PP2A), and the large T antigen (LT) binds pRb, p107, p130, and p53. However, the MWPyV LT was less stable than the simian virus 40 (SV40) LT and was unable to promote the growth of normal cells. This report confirms that MWPyV is a widespread human virus expressing T antigens with low transforming potential. C1 [Berrios, Christian; Pedamallu, Chandrasekhar; Duke, Fujiko; Marcelus, Christina; Cheng, Jingwei; Meyerson, Matthew; DeCaprio, James A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Berrios, Christian; DeCaprio, James A.] Harvard Univ, Grad Sch Arts & Sci, Div Med Sci, Program Virol, Boston, MA 02115 USA. [Jung, Joonil; Pedamallu, Chandrasekhar; Duke, Fujiko; Meyerson, Matthew] Broad Inst MIT & Harvard, Cambridge, MA USA. [Primi, Blake; Garcea, Robert L.] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA. [Primi, Blake; Garcea, Robert L.] Univ Colorado, BioFrontiers Inst, Boulder, CO 80309 USA. [Wang, Michael] Univ Colorado, Sch Med, Dept Pediat, Denver, CO USA. [Cheng, Jingwei; DeCaprio, James A.] Brigham & Womens Hosp, Dept Med, Boston, MA USA. [Cheng, Jingwei; DeCaprio, James A.] Harvard Univ, Sch Med, Boston, MA USA. [Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP DeCaprio, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM james_decaprio@dfci.harvard.edu FU Public Health Service [P01CA050661, RO1CA93804, R01CA63113, R0137667, 5T32AI007245, F31CA177274]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [DK 63829, 63861, 63821, 63865, 63863, 63836, 63790, UC4DK095300, HHSN267200700014C]; National Institute of Allergy and Infectious Diseases (NIAID); National Institute of Child Health and Human Development (NICHD); National Institute of Environmental Health Sciences (NIEHS); Juvenile Diabetes Research Foundation (JDRF); Centers for Disease Control and Prevention (CDC) FX This work was supported in part by Public Health Service grants P01CA050661, RO1CA93804, and R01CA63113 to J.A.D. and R0137667 to R.L.G. and training grants 5T32AI007245 and F31CA177274 to C.B.; The work described in this article was funded by DK 63829, 63861, 63821, 63865, 63863, 63836, 63790, and UC4DK095300 and contract no. HHSN267200700014C from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute of Child Health and Human Development (NICHD), the National Institute of Environmental Health Sciences (NIEHS), the Juvenile Diabetes Research Foundation (JDRF), and the Centers for Disease Control and Prevention (CDC). NR 41 TC 9 Z9 9 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD JAN PY 2015 VL 89 IS 1 BP 857 EP 862 DI 10.1128/JVI.02328-14 PG 6 WC Virology SC Virology GA AX8RL UT WOS:000347176100072 PM 25320321 ER PT J AU Wilson, JG Liu, KD Zhuo, NJ Caballero, L McMillan, M Fang, XH Cosgrove, K Vojnik, R Calfee, CS Lee, JW Rogers, AJ Levitt, J Wiener-Kronish, J Bajwa, EK Leavitt, A McKenna, D Thompson, BT Matthay, MA AF Wilson, Jennifer G. Liu, Kathleen D. Zhuo, Nanjing Caballero, Lizette McMillan, Melanie Fang, Xiaohui Cosgrove, Katherine Vojnik, Rosemary Calfee, Carolyn S. Lee, Jae-Woo Rogers, Angela J. Levitt, Joseph Wiener-Kronish, Jeanine Bajwa, Ednan K. Leavitt, Andrew McKenna, David Thompson, B. Taylor Matthay, Michael A. TI Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial SO LANCET RESPIRATORY MEDICINE LA English DT Article ID ACUTE LUNG INJURY; RESPIRATORY-DISTRESS-SYNDROME; BACTERIAL CLEARANCE; SEPSIS; SURVIVAL; REDUCE; SCORE; INFLAMMATION; DEFINITION; PNEUMONIA AB Background No effective pharmacotherapy for acute respiratory distress syndrome (ARDS) exists, and mortality remains high. Preclinical studies support the efficacy of mesenchymal stem (stromal) cells (MSCs) in the treatment of lung injury. We aimed to test the safety of a single dose of allogeneic bone marrow-derived MSCs in patients with moderate-to-severe ARDS. Methods The STem cells for ARDS Treatment (START) trial was a multicentre, open-label, dose-escalation, phase 1 clinical trial. Patients were enrolled in the intensive care units at University of California, San Francisco, CA, USA, Stanford University, Stanford, CA, USA, and Massachusetts General Hospital, Boston, MA, USA, between July 8, 2013, and Jan 13, 2014. Patients were included if they had moderate-to-severe ARDS as defined by the acute onset of the need for positive pressure ventilation by an endotracheal or tracheal tube, a PaO2:FiO(2) less than 200 mm Hg with at least 8 cm H2O positive end-expiratory airway pressure (PEEP), and bilateral infiltrates consistent with pulmonary oedema on frontal chest radiograph. The first three patients were treated with low dose MSCs (1 million cells/kg predicted bodyvveight [PBW]), the next three patients received intermediate dose MSCs (5 million cells/kg PBW), and the final three patients received high dose MSCs (10 million cells/kg PBW). Primary outcomes included the incidence of prespecified infusion-associated events and serious adverse events. The trial is registered with ClinicalTrials.gov, number NCT01775774. Findings No prespecified infusion-associated events or treatment-related adverse events were reported in any of the nine patients. Serious adverse events were subsequently noted in three patients during the weeks after the infusion: one patient died on study day 9, one patient died on study day 31, and one patient was discovered to have multiple embolic infarcts of the spleen, kidneys, and brain that were age-indeterminate, but thought to have occurred before the MSC infusion based on MRI results. None of these severe adverse events were thought to be MSC-related. Interpretation A single intravenous infusion of allogeneic, bone marrow-derived human MSCs was well tolerated in nine patients with moderate to severe ARDS. Based on this phase 1 experience, we have proceeded to phase 2 testing of MSCs for moderate to severe ARDS with a primary focus on safety and secondary outcomes including respiratory, systemic, and biological endpoints. C1 [Wilson, Jennifer G.] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA. [Wilson, Jennifer G.; Liu, Kathleen D.; Calfee, Carolyn S.; Lee, Jae-Woo; Matthay, Michael A.] Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. [Liu, Kathleen D.; Calfee, Carolyn S.; Matthay, Michael A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Liu, Kathleen D.; Zhuo, Nanjing; Fang, Xiaohui; Calfee, Carolyn S.; Matthay, Michael A.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Caballero, Lizette; McMillan, Melanie] Univ Calif San Francisco, Clin Labs, Blood & MarrowTransplant Lab, San Francisco, CA 94143 USA. [Cosgrove, Katherine; Bajwa, Ednan K.; Thompson, B. Taylor] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Vojnik, Rosemary; Rogers, Angela J.; Levitt, Joseph] Stanford Univ, Dept Med, Div Pulm & Crit Care Med, Stanford, CA 94305 USA. [Wiener-Kronish, Jeanine] Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Cambridge, MA 02138 USA. [Leavitt, Andrew] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. [McKenna, David] Univ Minnesota, Dept Lab Med & Pathol, Div Transfus Med, Minneapolis, MN 55455 USA. RP Matthay, MA (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. EM michael.matthay@ucsf.edu FU NHLBI [U01 HL10871301]; NIH/NCRR UCSF-CTSI Grant [RR024131]; NIH-supported Production Assistance for Cellular Therapies group (Molecular and Cellular Therapeutics, University of Minnesota) [HHSN268201000008C] FX This trial was supported by NHLBI U01 HL10871301, an NIH/NCRR UCSF-CTSI Grant RR024131 (T1 Catalyst Award), and the NIH-supported Production Assistance for Cellular Therapies group (Molecular and Cellular Therapeutics, University of Minnesota), Contract # HHSN268201000008C. The authors also appreciate the support of the intensive care nursing at UCSF, Stanford Medical Center, and the Massachusetts General Hospital. We appreciate the work of Jason Abbott who did the biological measurements, and Brian Daniel, who assisted with adherence to the ARDS Network lung protective ventilation protocol. The authors also thank the Data Safety Monitoring Board (Gordon Bernard, Chair; Herbert Wiedemann, and Kevin Delucchi), and the Medical Monitor (Marc Moss). NR 35 TC 61 Z9 64 U1 4 U2 20 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-2600 J9 LANCET RESP MED JI Lancet Resp. Med. PD JAN PY 2015 VL 3 IS 1 BP 24 EP 32 DI 10.1016/52213-2600(14)70291-7 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AY1PZ UT WOS:000347365900018 PM 25529339 ER PT J AU Lochhead, P Chan, AT Nishihara, R Fuchs, CS Beck, AH Giovannucci, E Ogino, S AF Lochhead, Paul Chan, Andrew T. Nishihara, Reiko Fuchs, Charles S. Beck, Andrew H. Giovannucci, Edward Ogino, Shuji TI Etiologic field effect: reappraisal of the field effect concept in cancer predisposition and progression SO MODERN PATHOLOGY LA English DT Article ID ISLAND METHYLATOR PHENOTYPE; LIFE-STYLE FACTORS; MOLECULAR PATHOLOGICAL EPIDEMIOLOGY; ONE-CARBON METABOLISM; MICROSATELLITE INSTABILITY STATUS; MGMT PROMOTER METHYLATION; BODY-MASS INDEX; HELICOBACTER-PYLORI INFECTION; CONTRALATERAL BREAST-CANCER; SPORADIC COLORECTAL-CANCER AB The term 'field effect' (also known as field defect, field cancerization, or field carcinogenesis) has been used to describe a field of cellular and molecular alteration, which predisposes to the development of neoplasms within that territory. We explore an expanded, integrative concept, 'etiologic field effect', which asserts that various etiologic factors (the exposome including dietary, lifestyle, environmental, microbial, hormonal, and genetic factors) and their interactions (the interactome) contribute to a tissue microenvironmental milieu that constitutes a 'field of susceptibility' to neoplasia initiation, evolution, and progression. Importantly, etiological fields predate the acquisition of molecular aberrations commonly considered to indicate presence of filed effect. Inspired by molecular pathological epidemiology (MPE) research, which examines the influence of etiologic factors on cellular and molecular alterations during disease course, an etiologically focused approach to field effect can: (1) broaden the horizons of our inquiry into cancer susceptibility and progression at molecular, cellular, and environmental levels, during all stages of tumor evolution; (2) embrace host-environment-tumor interactions (including gene-environment interactions) occurring in the tumor microenvironment; and, (3) help explain intriguing observations, such as shared molecular features between bilateral primary breast carcinomas, and between synchronous colorectal cancers, where similar molecular changes are absent from intervening normal colon. MPE research has identified a number of endogenous and environmental exposures which can influence not only molecular signatures in the genome, epigenome, transcriptome, proteome, metabolome and interactome, but also host immunity and tumor behavior. We anticipate that future technological advances will allow the development of in vivo biosensors capable of detecting and quantifying 'etiologic field effect' as abnormal network pathology patterns of cellular and microenvironmental responses to endogenous and exogenous exposures. Through an 'etiologic field effect' paradigm, and holistic systems pathology (systems biology) approaches to cancer biology, we can improve personalized prevention and treatment strategies for precision medicine. C1 [Lochhead, Paul] Univ Aberdeen, Gastrointestinal Res Grp, Inst Med Sci, Aberdeen AB25 2ZD, Scotland. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.; Fuchs, Charles S.; Giovannucci, Edward] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med,Dept Med, Boston, MA 02115 USA. [Nishihara, Reiko; Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Nishihara, Reiko; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Beck, Andrew H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. [Giovannucci, Edward; Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Ogino, Shuji] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Lochhead, P (reprint author), Univ Aberdeen, Gastrointestinal Res Grp, Inst Med Sci, Foresterhill, Aberdeen AB25 2ZD, Scotland. EM paul.lochhead@abdn.ac.uk; shuji_ogino@dfci.harvard.edu FU USA National Institute of Health (NIH) [R01 CA151993, R01 CA137178, P50 CA127003]; Frank Knox Memorial Fellowship from Harvard University FX This work was supported by USA National Institute of Health (NIH) (R01 CA151993 (to SO), R01 CA137178 (to ATC), and P50 CA127003 (to CSF)). PL is a Scottish Government clinical academic fellow, and was supported by a Frank Knox Memorial Fellowship from Harvard University. ATC is a Damon Runyon Clinical Investigator. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH. Funding agencies did not have any role in the decision to submit the manuscript for publication, or the writing of the manuscript. The following standardized official symbols were used: HUGO (Human Genome Organization)-approved official symbols for genes and gene products, including BRAF, ERBB2, ESR1, FASN, KRAS, MGMT, MLH1, PGR, and PTGS2, all of which are described at www.genenames.org. NR 244 TC 22 Z9 22 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2015 VL 28 IS 1 BP 14 EP 29 DI 10.1038/modpathol.2014.81 PG 16 WC Pathology SC Pathology GA AY1XY UT WOS:000347384200002 PM 24925058 ER PT J AU Martinez-Quintanilla, J He, D Wakimoto, H Alemany, R Shah, K AF Martinez-Quintanilla, Jordi He, Derek Wakimoto, Hiroaki Alemany, Ramon Shah, Khalid TI Encapsulated Stem Cells Loaded With Hyaluronidase-expressing Oncolytic Virus for Brain Tumor Therapy SO MOLECULAR THERAPY LA English DT Article ID PHASE-I TRIAL; GENE-THERAPY; EXTRACELLULAR-MATRIX; HUMAN GLIOBLASTOMA; MALIGNANT GLIOMA; CANCER-THERAPY; VIRAL THERAPY; ADENOVIRUS; EFFICACY; VIROTHERAPY AB Despite the proven safety of oncolytic viruses (OV) in clinical trials for glioblastoma (GBM), their efficacy has been hindered by suboptimal spreading within the tumor. We show that hyaluronan or hyaluronic acid (HA), an important component of extracellular matrix (ECM), is highly expressed in a majority of tumor xenografts established from patient-derived GBM lines that present both invasive and nodular phenotypes. Intratumoral injection of a conditionally replicating adenovirus expressing soluble hyaluronidase (ICOVIR17) into nodular GBM, mediated HA degradation and enhanced viral spread, resulting in a significant antitumor effect and mice survival. In an effort to translate OV-based therapeutics into clinical settings, we encapsulated human adipose-derived mesenchymal stem cells (MSC) loaded with ICOVIR17 in biocompatible synthetic extracellular matrix (sECM) and tested their efficacy in a clinically relevant mouse model of GBM resection. Compared with direct injection of ICOVIR17, sECM-MSC loaded with ICOVIR17 resulted in a significant decrease in tumor regrowth and increased mice survival. This is the first report of its kind revealing the expression of HA in GBM and the role of OV-mediated HA targeting in clinically relevant mouse model of GBM resection and thus has clinical implications. C1 [Martinez-Quintanilla, Jordi; He, Derek; Wakimoto, Hiroaki; Shah, Khalid] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurotherapy & Imaging Lab, Boston, MA USA. [Martinez-Quintanilla, Jordi; He, Derek; Wakimoto, Hiroaki; Shah, Khalid] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wakimoto, Hiroaki] Harvard Univ, Sch Med, Dept Neurosurg, Massachusetts Gen Hosp, Boston, MA USA. [Alemany, Ramon] IDIBELL Inst Catala Oncol, Lab Recerca Traslac, Lhospitalet De Llobregat, Catalonia, Spain. [Shah, Khalid] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Shah, Khalid] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Shah, K (reprint author), Massachusetts Gen Hosp, Dept Radiol, 13th St,149 Bldg, Charlestown, MA 02129 USA. EM kshah@mgh.harvard.edu FU Ministerio de Educacion of Spain [RO1 CA138922, RO1 NS071197]; James McDonnell Foundation FX We thank Juan J. Rojas and Sonia Guedan for engineering ICOVIR15 and ICOVIR17, respectively, and Rafael Moreno, Cristina Puig, Alba Rodriguez, and Raul Gil for their help and advice in adenovirus techniques. We also acknowledge Manel Cascallo and VCN Biosciences for kindly allowing us to use ICOVIR17. This work was supported by Ministerio de Educacion of Spain (J.M.-Q.), RO1 CA138922 (K.S.), RO1 NS071197 (K.S.), and James McDonnell Foundation (K.S.). NR 50 TC 12 Z9 12 U1 1 U2 23 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD JAN PY 2015 VL 23 IS 1 BP 108 EP 118 DI 10.1038/mt.2014.204 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AY2ZG UT WOS:000347453900014 PM 25352242 ER PT J AU Ajroud-Driss, S Fecto, F Ajroud, K Lalani, I Calvo, SE Mootha, VK Deng, HX Siddique, N Tahmoush, AJ Heiman-Patterson, TD Siddique, T AF Ajroud-Driss, Senda Fecto, Faisal Ajroud, Kaouther Lalani, Irfan Calvo, Sarah E. Mootha, Vamsi K. Deng, Han-Xiang Siddique, Nailah Tahmoush, Albert J. Heiman-Patterson, Terry D. Siddique, Teepu TI Mutation in the novel nuclear-encoded mitochondrial protein CHCHD10 in a family with autosomal dominant mitochondrial myopathy SO NEUROGENETICS LA English DT Article DE Mitochondrial myopathy; Genetics; CHCHD10; Mitochondria ID DISEASE; GENOME AB Mitochondrial myopathies belong to a larger group of systemic diseases caused by morphological or biochemical abnormalities of mitochondria. Mitochondrial disorders can be caused by mutations in either the mitochondrial or nuclear genome. Only 5 % of all mitochondrial disorders are autosomal dominant. We analyzed DNA from members of the previously reported Puerto Rican kindred with an autosomal dominant mitochondrial myopathy (Heimann-Patterson et al. 1997). Linkage analysis suggested a putative locus on the pericentric region of the long arm of chromosome 22 (22q11). Using the tools of integrative genomics, we established chromosome 22 open reading frame 16 (C22orf16) (later designated as CHCHD10) as the only high-scoring mitochondrial candidate gene in our minimal candidate region. Sequence analysis revealed a double-missense mutation (R15S and G58R) in cis in CHCHD10 which encodes a coiled coil-helix-coiled coil-helix protein of unknown function. These two mutations completely co-segregated with the disease phenotype and were absent in 1,481 Caucasian and 80 Hispanic (including 32 Puerto Rican) controls. Expression profiling showed that CHCHD10 is enriched in skeletal muscle. Mitochondrial localization of the CHCHD10 protein was confirmed using immunofluorescence in cells expressing either wild-type or mutant CHCHD10. We found that the expression of the G58R, but not the R15S, mutation induced mitochondrial fragmentation. Our findings identify a novel gene causing mitochondrial myopathy, thereby expanding the spectrum of mitochondrial myopathies caused by nuclear genes. Our findings also suggest a role for CHCHD10 in the morphologic remodeling of the mitochondria. C1 [Ajroud-Driss, Senda; Fecto, Faisal; Ajroud, Kaouther; Lalani, Irfan; Deng, Han-Xiang; Siddique, Nailah; Siddique, Teepu] Northwestern Univ, Feinberg Sch Med, Ken & Ruth Davee Dept Neurol & Clin Neurosci, Div Neuromuscular Med, Chicago, IL 60611 USA. [Siddique, Teepu] Northwestern Univ, Interdepartmental Neurosci Program, Chicago, IL 60611 USA. [Siddique, Teepu] Northwestern Univ, Feinberg Sch Med, Dept Cell & Mol Biol, Chicago, IL 60611 USA. [Calvo, Sarah E.; Mootha, Vamsi K.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Calvo, Sarah E.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Calvo, Sarah E.; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Calvo, Sarah E.; Mootha, Vamsi K.] Broad Inst, Cambridge, MA USA. [Tahmoush, Albert J.; Heiman-Patterson, Terry D.] Thomas Jefferson Univ, Dept Neurol, Philadelphia, PA 19107 USA. RP Ajroud-Driss, S (reprint author), Northwestern Univ, Feinberg Sch Med, Ken & Ruth Davee Dept Neurol & Clin Neurosci, Div Neuromuscular Med, Chicago, IL 60611 USA. EM s-ajroud@northwestern.edu; t-siddique@northwestern.edu FU National Institute of Neurological Disorders and Stroke [NS050641]; Les Turner ALS Foundation/Herbert C. Wenske Foundation Professorship; David C. Asselin MD Memorial Fund; Vena E. Schaff ALS Research Fund; George Link, Jr. Foundation; Foglia Family Foundation; National Institutes of Health [R01GM097136]; NCI CCSG [P30 CA060553] FX We thank the patients and their family members for participating in this study. We also thank Kreshnik B. Ahmeti, LiJun Cheng, and Yi Yang for their technical assistance. This work was supported by the National Institute of Neurological Disorders and Stroke (NS050641); the Les Turner ALS Foundation/Herbert C. Wenske Foundation Professorship; the David C. Asselin MD Memorial Fund; the Vena E. Schaff ALS Research Fund; the George Link, Jr. Foundation; and the Foglia Family Foundation. This work was supported by a grant (R01GM097136) from the National Institutes of Health to VKM. Imaging work was performed at the Northwestern University Cell Imaging Facility generously supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center. NR 25 TC 21 Z9 22 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1364-6745 EI 1364-6753 J9 NEUROGENETICS JI Neurogenetics PD JAN PY 2015 VL 16 IS 1 BP 1 EP 9 DI 10.1007/s10048-014-0421-1 PG 9 WC Genetics & Heredity; Clinical Neurology SC Genetics & Heredity; Neurosciences & Neurology GA AY2HE UT WOS:000347408700001 PM 25193783 ER PT J AU Treister, R Eisenberg, E Demeter, N Pud, D AF Treister, Roi Eisenberg, Elon Demeter, Naor Pud, Dorit TI Alterations in Pain Response are Partially Reversed by Methylphenidate (Ritalin) in Adults with Attention Deficit Hyperactivity Disorder (ADHD) SO PAIN PRACTICE LA English DT Article DE attention deficit hyperactivity disorder; dopamine; experimental pain; pain threshold; pain tolerance; methylphenidate ID RESTLESS LEGS SYNDROME; DEFICIT/HYPERACTIVITY DISORDER; CLINICAL EFFECTIVENESS; PRESCHOOL-CHILDREN; RELIEVE PAIN; DOPAMINE; LEVODOPA; SYMPTOMS; EFFICACY; PET AB BackgroundAttention deficit hyperactivity disorder (ADHD) is characterized by dysregulation of sensory processing and neurobiology of dopamine. Although cumulative evidence suggests that dopamine is involved in pain processing, pain perception in ADHD subjects and the effect of dopamine agonists such as methylphenidate (MP, Ritalin) on it have rarely been studied. AimsThe aims of this study were to (1) psychophysically assess sensitivity to pain in ADHD subjects as compared to controls and (2) examine the effects of MP on pain response in ADHD subjects. MethodsThirty subjects with ADHD and 30 age- and gender-matched controls participated in a preliminary trial. Pain threshold, intensity, and tolerance in response to cold pain stimulation were measured for both groups (ADHD with no treatment). In addition, the ADHD group was reassessed following a single dose of MP treatment. ResultsThe ADHD subjects without MP in comparison with controls displayed significantly shorter cold pain threshold (2.82.1 vs. 5.8 +/- 2.5seconds, respectively, P<0.001) and cold tolerance (21.8 +/- 22.3 vs. 62.8 +/- 59.8seconds, respectively P<0.001). No differences in pain intensities between the groups were found. Following MP treatment, both cold threshold and tolerance in the ADHD subjects increased significantly compared to those with no treatment (3.6 +/- 2.5seconds, P=0.011, and 46.4 +/- 53.3seconds, P<0.001, respectively). ConclusionsThese results suggest that adults with ADHD are more sensitive to pain compared with controls and that MP may exert antinociceptive properties in these subjects. Randomized, controlled trials are warranted to verify these findings. C1 [Treister, Roi] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Eisenberg, Elon] Rambam Hlth Care Campus, Inst Pain Med, Haifa, Israel. [Eisenberg, Elon] Technion Israel Inst Technol, Rappaport Fac Med, Haifa, Israel. [Demeter, Naor; Pud, Dorit] Univ Haifa, Fac Social Welf & Hlth Sci, IL-31999 Haifa, Israel. RP Treister, R (reprint author), Massachusetts Gen Hosp, Nerve Injury Unit, Warren 310, Boston, MA 02114 USA. EM treister.roi@gmail.com NR 48 TC 7 Z9 7 U1 3 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1530-7085 EI 1533-2500 J9 PAIN PRACT JI Pain Pract. PD JAN PY 2015 VL 15 IS 1 BP 4 EP 11 DI 10.1111/papr.12129 PG 8 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA AY1XO UT WOS:000347383100006 PM 24134430 ER PT J AU Vassy, JL Christensen, KD Slashinski, MJ Lautenbach, DM Raghavan, S Robinson, JO Blumenthal-Barby, J Feuerman, LZ Lehmann, LS Murray, MF Green, RC McGuire, AL AF Vassy, Jason L. Christensen, Kurt D. Slashinski, Melody J. Lautenbach, Denise M. Raghavan, Sridharan Robinson, Jill Oliver Blumenthal-Barby, Jennifer Feuerman, Lindsay Zausmer Lehmann, Lisa Soleymani Murray, Michael F. Green, Robert C. McGuire, Amy L. TI 'Someday it will be the norm': physician perspectives on the utility of genome sequencing for patient care in the MedSeq Project SO PERSONALIZED MEDICINE LA English DT Article DE genomics; high-throughput nucleotide sequencing; pharmacogenetics; physician's practice patterns; qualitative research ID PERSONALIZED MEDICINE; CONSUMER GENOMICS; RANDOMIZED-TRIAL; CANCER-RISK; INFORMATION; POPULATION; PREVENTION; EXPERIENCE; GENETICS; DISEASES AB Aim: To describe practicing physicians' perceived clinical utility of genome sequencing. Materials & methods: We conducted a mixed-methods analysis of data from 18 primary care physicians and cardiologists in a study of the clinical integration of whole-genome sequencing. Physicians underwent brief genomics continuing medical education before completing surveys and semi-structured interviews. Results: Physicians described sequencing as currently lacking clinical utility because of its uncertain interpretation and limited impact on clinical decision-making, but they expressed the idea that its clinical integration was inevitable. Potential clinical uses for sequencing included complementing other clinical information, risk stratification, motivating patient behavior change and pharmacogenetics. Conclusion: Physicians given genomics continuing medical education use the language of both evidence-based and personalized medicine in describing the utility of genome-wide testing in patient care. C1 [Vassy, Jason L.] VA Boston Healthcare Syst, Gen Internal Med Sect, Boston, MA 02130 USA. [Vassy, Jason L.; Lehmann, Lisa Soleymani] Brigham & Womens Hosp, Dept Med, Div Gen Med & Primary Care, Boston, MA 02115 USA. [Vassy, Jason L.; Christensen, Kurt D.; Lautenbach, Denise M.; Raghavan, Sridharan; Lehmann, Lisa Soleymani; Green, Robert C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Christensen, Kurt D.; Lautenbach, Denise M.; Green, Robert C.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Slashinski, Melody J.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA. [Raghavan, Sridharan; Lehmann, Lisa Soleymani] Massachusetts Gen Hosp, Gen Med Div, Boston, MA 02114 USA. [Robinson, Jill Oliver; Blumenthal-Barby, Jennifer; Feuerman, Lindsay Zausmer; McGuire, Amy L.] Baylor Coll Med, Ctr Med Eth & Hlth Policy, Houston, TX 77030 USA. Harvard Univ, Sch Med, Ctr Bioeth, Boston, MA 02115 USA. [Murray, Michael F.] Geisinger Hlth Syst, Danville, PA 17822 USA. RP Vassy, JL (reprint author), VA Boston Healthcare Syst, Gen Internal Med Sect, Boston, MA 02130 USA. EM jvassy@partners.org FU US National Institutes of Health [U01-HG006500, U19-HD077671, L30-DK089597, F32-HG006993] FX This work was supported the US National Institutes of Health (U01-HG006500, U19-HD077671, L30-DK089597, F32-HG006993). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 53 TC 5 Z9 5 U1 2 U2 6 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 EI 1744-828X J9 PERS MED JI Pers. Med. PY 2015 VL 12 IS 1 BP 23 EP 32 DI 10.2217/PME.14.68 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AY3DD UT WOS:000347463800005 PM 25642274 ER PT J AU Choi, M Kwok, SJJ Yun, SH AF Choi, Myunghwan Kwok, Sheldon J. J. Yun, Seok Hyun TI In Vivo Fluorescence Microscopy: Lessons From Observing Cell Behavior in Their Native Environment SO PHYSIOLOGY LA English DT Review ID REAL-TIME; INTRAVITAL MICROSCOPY; HIGH-RESOLUTION; BLOOD-FLOW; STEM-CELL; IMAGING REVEALS; BONE-MARROW; SPINAL-CORD; NEUTROPHIL EXTRAVASATION; 2-PHOTON MICROSCOPY AB Microscopic imaging techniques to visualize cellular behaviors in their natural environment play a pivotal role in biomedical research. Here, we review how recent technical advances in intravital microscopy have enabled unprecedented access to cellular physiology in various organs of mice in normal and diseased states. C1 [Choi, Myunghwan; Kwok, Sheldon J. J.; Yun, Seok Hyun] Harvard Univ, Sch Med, Boston, MA 02163 USA. [Choi, Myunghwan; Kwok, Sheldon J. J.; Yun, Seok Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Kwok, Sheldon J. J.; Yun, Seok Hyun] Harvard MIT Hlth Sci & Technol, Cambridge, MA USA. RP Choi, M (reprint author), Harvard Univ, Sch Med, Boston, MA 02163 USA. EM syun@hms.harvard.edu OI Choi, Myunghwan/0000-0002-4235-7003 FU U.S. National Institutes of Health [U54 CA-143837, P41 EB-015903]; U.S. National Science of Foundation [ECS-1101947]; National Research Foundation of Korea [NRF-2013R1A6A3A03060958] FX This work was funded in part by the U.S. National Institutes of Health (U54 CA-143837, P41 EB-015903), the U.S. National Science of Foundation (ECS-1101947), and a postdoctoral fellowship from the National Research Foundation of Korea (NRF-2013R1A6A3A03060958). NR 118 TC 4 Z9 4 U1 4 U2 16 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1548-9213 EI 1548-9221 J9 PHYSIOLOGY JI Physiology PD JAN 1 PY 2015 VL 30 IS 1 BP 40 EP 49 DI 10.1152/physiol.00019.2014 PG 10 WC Physiology SC Physiology GA AY0SD UT WOS:000347306100007 PM 25559154 ER PT J AU Spiegel, BMR Reid, MW Bolus, R Whitman, CB Talley, J Dea, S Shahedi, K Karsan, H Teal, C Melmed, GY Cohen, E Fuller, G Yen, L Hodgkins, P Erder, MH AF Spiegel, Brennan M. R. Reid, Mark W. Bolus, Roger Whitman, Cynthia B. Talley, Jennifer Dea, Stanley Shahedi, Kamyar Karsan, Hetal Teal, Chassidy Melmed, Gil Y. Cohen, Erica Fuller, Garth Yen, Linnette Hodgkins, Paul Erder, M. Haim TI Development and validation of a disease-targeted quality of life instrument for chronic diverticular disease: the DV-QOL SO QUALITY OF LIFE RESEARCH LA English DT Article DE Patient-reported outcomes; Health-related quality of life; Diverticulosis; Diverticulitis ID IRRITABLE-BOWEL-SYNDROME; INFORMATION-SYSTEM PROMIS; UNITED-STATES; SIGMOID DIVERTICULITIS; PRACTICE PARAMETERS; COLON; DIAGNOSIS; FRAMEWORK; SYMPTOMS; PATTERNS AB Colonic diverticular disease is typically conceived as acute diverticulitis attacks surrounded by periods of clinical silence. However, evolving data indicate that many patients have persistent symptoms and diminished health-related quality of life (HRQOL) long after acute attacks. We developed a disease-targeted HRQOL measure for symptomatic uncomplicated diverticular disease (SUDD)-the diverticulitis quality of life (DV-QOL) instrument. We conducted a systematic literature review to craft a conceptual model of SUDD HRQOL. This was complemented by three focus groups including 45 SUDD patients. We developed items based on our literature search, focus groups, and cognitive debriefings. We administered the items to SUDD patients with persistent symptoms following a confirmed diverticulitis event. We created scales based on factor analysis and evaluated the scales for reliability and validity. Concept elicitation revealed a range of illness experiences attributed to SUDD. Coding of 20,490 transcribed words yielded a 52-code network with four primary, condition-related concepts: (1) physical symptoms (e.g., bloating); (2) behaviors (e.g., restrictions); (3) cognitions and concerns (e.g., fear); and (4) impact and consequences (e.g., absenteeism, anxiety). Based on patient language, we developed the 17-item DV-QOL instrument. In a cross-sectional validation sample of 197 patients, DV-QOL discriminated between patients with recent versus distant diverticulitis events and correlated highly with Short Form 36 and hospital anxiety and depression scores. Patients with SUDD attribute a wide range of negative psychological, social, and physical symptoms to their condition, both during and after acute attacks; DV-QOL captures these symptoms in a valid, reliable manner. C1 [Spiegel, Brennan M. R.; Reid, Mark W.; Talley, Jennifer; Cohen, Erica] VA Greater Los Angeles Healthcare Syst, Dept Gastroenterol, Los Angeles, CA 90073 USA. [Spiegel, Brennan M. R.; Bolus, Roger] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA. [Spiegel, Brennan M. R.; Fuller, Garth] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. [Spiegel, Brennan M. R.; Reid, Mark W.; Bolus, Roger; Whitman, Cynthia B.; Talley, Jennifer; Fuller, Garth] CS CORE, Los Angeles, CA USA. [Dea, Stanley; Shahedi, Kamyar] UCLA Olive View Med Ctr, Dept Gastroenterol, Los Angeles, CA USA. [Karsan, Hetal; Teal, Chassidy] Atlanta Gastroenterol Associates, Atlanta, GA USA. [Melmed, Gil Y.; Cohen, Erica] Cedars Sinai Med Ctr, Dept Gastroenterol, Los Angeles, CA 90048 USA. [Yen, Linnette; Hodgkins, Paul; Erder, M. Haim] Shire Dev LLC, Wayne, PA USA. RP Spiegel, BMR (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Gastroenterol, 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu FU Shire Development LLC; Amgen Pharmaceuticals; Ironwood Pharmaceuticals; Theravance Pharmaceuticals; Pfizer; Linnette Yen FX Brennan Spiegel has received research support from Amgen Pharmaceuticals, Ironwood Pharmaceuticals, Shire Development LLC, and Theravance Pharmaceuticals. Gil Melmed has consulted for Abbvie, Jannsen, Given Imaging, Celgene, and Luitpold. He has received research support from Pfizer, and been on the speaker's bureau for Abbott. Linnette Yen, deceased, was an employee of Shire and held stock/options in Shire. Paul Hodgkins and M. Haim Erder are Shire employees and own stock in the company. This study is supported by a research grant from Shire Development LLC. NR 43 TC 4 Z9 4 U1 0 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 EI 1573-2649 J9 QUAL LIFE RES JI Qual. Life Res. PD JAN PY 2015 VL 24 IS 1 BP 163 EP 179 DI 10.1007/s11136-014-0753-1 PG 17 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AY0OO UT WOS:000347296200016 PM 25059533 ER PT J AU Frank, MH Frank, NY AF Frank, Markus H. Frank, Natasha Y. TI Restoring the cornea from limbal stem cells SO REGENERATIVE MEDICINE LA English DT Editorial Material DE ABCB5; adult stem cell; cornea; corneal epithelial stem cells; knockout mouse; KRT12; limbal stem cells; limbal stem cell deficiency; limbus; PAX6; skin; stem cell therapy; transplantation ID EPITHELIUM; ABCB5 C1 [Frank, Markus H.] Boston Childrens Hosp, Transplant Res Program, Boston, MA 02115 USA. [Frank, Natasha Y.] Harvard Univ, Sch Med, Dept Med, VA Boston Healthcare Syst, Boston, MA 02132 USA. RP Frank, MH (reprint author), Boston Childrens Hosp, Transplant Res Program, 300 Longwood Ave, Boston, MA 02115 USA. EM markus.frank@childrens.harvard.edu; nfrank@partners.org FU BLRD VA [I01 BX000516]; NCI NIH HHS [R01 CA158467, R01CA113796, R01 CA113796, R01CA138231, R01CA158467, R01 CA138231]; RRD VA [I01 RX000989] NR 14 TC 6 Z9 6 U1 1 U2 7 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0751 EI 1746-076X J9 REGEN MED JI Regen. Med. PY 2015 VL 10 IS 1 BP 1 EP 4 DI 10.2217/RME.14.66 PG 4 WC Cell & Tissue Engineering; Engineering, Biomedical SC Cell Biology; Engineering GA AY3CI UT WOS:000347461700001 PM 25562345 ER PT J AU Miyabe, Y Miyabe, C Nanki, T AF Miyabe, Yoshishige Miyabe, Chie Nanki, Toshihiro TI Could retinoids be a potential treatment for rheumatic diseases? SO RHEUMATOLOGY INTERNATIONAL LA English DT Review DE Retinoid; T cells; B cells; Rheumatoid arthritis; Rheumatic diseases ID TUMOR-NECROSIS-FACTOR; VITAMIN-A; T-CELLS; DENDRITIC CELLS; SYNTHETIC RETINOIDS; ANTIBODY-PRODUCTION; COLLAGEN ARTHRITIS; SYSTEMIC-SCLEROSIS; ACID RECEPTORS; IN-VITRO AB Retinoid, a derivative of vitamin A, is a general term used to describe compounds that bind to and activate retinoic acid receptors [RARs (RAR alpha, RAR beta, and RAR gamma)] and/or retinoid X receptors [RXRs (RXR alpha, RXR beta, and RXR gamma)]. They have been shown to surpress the differentiation of Th1/Th17 cells and induce the development of Th1/regulatory T cells. They also affect the proliferation of B cells as both an inducer and suppressor. Furthermore, retinoids may induce the maturation of dendritic cells and production of interleukin-10 from monocytes/macrophages. We recently demonstrated that retinoids suppressed the production of reactive oxygen species, the release of elastase from neutrophils by inhibiting mitogen-activated protein kinase signals, and both the migration speed and chemotaxis directionality of neutrophils. Retinoids, such as all-trans retinoic acid and tamibarotene, were previously shown to have positive effects on animal models of several rheumatic diseases, including arthritis, myositis, and vasculitis in vivo. Moreover, retinoids have been used in a pilot study to effectively treat patients with lupus nephritis and systemic sclerosis. We herein reviewed the effects of retinoids on immune cells, animal models of rheumatic diseases, and rheumatic patients. C1 [Miyabe, Yoshishige; Miyabe, Chie] Harvard Univ, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis,Med Sch, Charlestown, MA 02129 USA. [Nanki, Toshihiro] Teikyo Univ, Dept Clin Res Med, Itabashi Ku, Tokyo 1738605, Japan. RP Nanki, T (reprint author), Teikyo Univ, Dept Clin Res Med, Itabashi Ku, 2-11-1 Kaga, Tokyo 1738605, Japan. EM nanki@med.teikyo-u.ac.jp FU Chugai Pharmaceutical Co., LTD.; Eisai Co., LTD.; Ono Pharmaceutical Co., LTD.; Mitsubishi Tanabe Pharma Corporation; Takeda Pharmaceutical Co., LTD; AbbVie Inc.; UCB Japan Co. Ltd.; Astellas Pharma Inc.; Pfizer Japan Inc.; Bristol-Myers Squibb; Santen Pharmaceutical Co., Ltd.; Taisho Toyama Pharmaceutical Co., Ltd.; Asahi Kasei Pharma Corporation FX Dr. Nanki reports grants and personal fees from Chugai Pharmaceutical Co., LTD., grants and personal fees from Eisai Co., LTD., grants from Ono Pharmaceutical Co., LTD., grants and personal fees from Mitsubishi Tanabe Pharma Corporation., grants and personal fees from Takeda Pharmaceutical Co., LTD, grants and personal fees from AbbVie Inc., personal fees from UCB Japan Co. Ltd., personal fees from Astellas Pharma Inc., grants from Pfizer Japan Inc., personal fees from Bristol-Myers Squibb, personal fees from Santen Pharmaceutical Co., Ltd., personal fees from Taisho Toyama Pharmaceutical Co., Ltd., and grants from Asahi Kasei Pharma Corporation outside the submitted work. NR 58 TC 3 Z9 3 U1 0 U2 6 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0172-8172 EI 1437-160X J9 RHEUMATOL INT JI Rheumatol. Int. PD JAN PY 2015 VL 35 IS 1 BP 35 EP 41 DI 10.1007/s00296-014-3067-2 PG 7 WC Rheumatology SC Rheumatology GA AX9WX UT WOS:000347251000004 PM 24939557 ER PT J AU Yeh, MW Bauer, AJ Bernet, VA Ferris, RL Loevner, LA Mandel, SJ Orloff, LA Randolph, GW Steward, DL AF Yeh, Michael W. Bauer, Andrew J. Bernet, Victor A. Ferris, Robert L. Loevner, Laurie A. Mandel, Susan J. Orloff, Lisa A. Randolph, Gregory W. Steward, David L. TI American Thyroid Association Statement on Preoperative Imaging for Thyroid Cancer Surgery SO THYROID LA English DT Article ID FINE-NEEDLE-ASPIRATION; POSITRON-EMISSION-TOMOGRAPHY; LYMPH-NODE METASTASES; COMPUTED-TOMOGRAPHY; ELEVATED THYROGLOBULIN; SURGICAL-MANAGEMENT; SERUM THYROGLOBULIN; CONTRAST AGENTS; FDG-PET/CT; CARCINOMA AB Background: The success of surgery for thyroid cancer hinges on thorough and accurate preoperative imaging, which enables complete clearance of the primary tumor and affected lymph node compartments. This working group was charged by the Surgical Affairs Committee of the American Thyroid Association to examine the available literature and to review the most appropriate imaging studies for the planning of initial and revision surgery for thyroid cancer. Summary: Ultrasound remains the most important imaging modality in the evaluation of thyroid cancer, and should be used routinely to assess both the primary tumor and all associated cervical lymph node basins preoperatively. Positive lymph nodes may be distinguished from normal nodes based upon size, shape, echogenicity, hypervascularity, loss of hilar architecture, and the presence of calcifications. Ultrasound-guided fine-needle aspiration of suspicious lymph nodes may be useful in guiding the extent of surgery. Cross-sectional imaging (computed tomography with contrast or magnetic resonance imaging) may be considered in select circumstances to better characterize tumor invasion and bulky, inferiorly located, or posteriorly located lymph nodes, or when ultrasound expertise is not available. The above recommendations are applicable to both initial and revision surgery. Functional imaging with positron emission tomography (PET) or PET-CT may be helpful in cases of recurrent cancer with positive tumor markers and negative anatomic imaging. C1 [Yeh, Michael W.] Univ Calif Los Angeles, David Geffen Sch Med, Sect Endocrine Surg, Los Angeles, CA 90095 USA. [Bauer, Andrew J.] Childrens Hosp Philadelphia, Div Endocrinol & Diabet, Thyroid Ctr, Philadelphia, PA 19104 USA. [Bernet, Victor A.] Mayo Clin & Mayo Grad Sch Med, Div Endocrinol, Jacksonville, FL USA. [Ferris, Robert L.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Loevner, Laurie A.; Mandel, Susan J.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Orloff, Lisa A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Randolph, Gregory W.] Massachusetts Gen Hosp, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Steward, David L.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. RP Yeh, MW (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Sect Endocrine Surg, 10833 Le Conte Ave 72-228 CHS, Los Angeles, CA 90095 USA. EM myeh@mednet.ucla.edu FU NCI NIH HHS [P50 CA097190] NR 61 TC 18 Z9 19 U1 1 U2 9 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD JAN 1 PY 2015 VL 25 IS 1 BP 3 EP 14 DI 10.1089/thy.2014.0096 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AY4GP UT WOS:000347536600002 PM 25188202 ER PT J AU Latif, R Ali, MR Ma, RS David, M Morshed, SA Ohlmeyer, M Felsenfeld, DP Lau, Z Mezei, M Davies, TF AF Latif, Rauf Ali, M. Rejwan Ma, Risheng David, Martine Morshed, Syed A. Ohlmeyer, Michael Felsenfeld, Dan P. Lau, Zerlina Mezei, Mihaly Davies, Terry F. TI New Small Molecule Agonists to the Thyrotropin Receptor SO THYROID LA English DT Article ID STIMULATING HORMONE-RECEPTOR; THROUGHPUT SCREENING ASSAYS; PROTEIN-COUPLED RECEPTOR; TSH RECEPTOR; SIGNAL-TRANSDUCTION; THYROID-FUNCTION; GRAVES-DISEASE; HINGE REGION; CRYSTAL-STRUCTURE; LIGAND-BINDING AB Background: Novel small molecular ligands (SMLs) to the thyrotropin receptor (TSHR) have potential as improved molecular probes and as therapeutic agents for the treatment of thyroid dysfunction and thyroid cancer. Methods: To identify novel SMLs to the TSHR, we developed a transcription-based luciferase-cAMP high-throughput screening system and we screened 48,224 compounds from a 100K library in duplicate. Results: We obtained 62 hits using the cut-off criteria of the mean +/- three standard deviations above the baseline. Twenty molecules with the greatest activity were rescreened against the parent CHO-luciferase cell for nonspecific activation, and we selected two molecules (MS437 and MS438) with the highest potency for further study. These lead molecules demonstrated no detectible cross-reactivity with homologous receptors when tested against luteinizing hormone (LH)/human chorionic gonadotropin receptor and follicle stimulating hormone receptor-expressing cells. Molecule MS437 had a TSHR-stimulating potency with an EC50 of 13x10(-8) M, and molecule MS438 had an EC50 of 5.3x10(-8) M. The ability of these small molecule agonists to bind to the transmembrane domain of the receptor and initiate signal transduction was suggested by their activation of a chimeric receptor consisting of an LHR ectodomain and a TSHR transmembrane. Molecular modeling demonstrated that these molecules bound to residues S505 and E506 for MS438 and T501 for MS437 in the intrahelical region of transmembrane helix 3. We also examined the G protein activating ability of these molecules using CHO cells co-expressing TSHRs transfected with luciferase reporter vectors in order to measure G(s alpha), G(beta gamma), G(alpha q), and G(alpha 12) activation quantitatively. The MS437 and MS438 molecules showed potent activation of G(s alpha), G(alpha q), and G(alpha 12) similar to TSH, but neither the small molecule agonists nor TSH showed activation of the G(beta gamma) pathway. The small molecules MS437 and MS438 also showed upregulation of thyroglobulin (Tg), sodium iodine symporter (NIS), and TSHR gene expression. Conclusions: Pharmacokinetic analysis of MS437 and MS438 indicated their pharmacotherapeutic potential, and their intraperitoneal administration to normal female mice resulted in significantly increased serum thyroxine levels, which could be maintained by repeated treatments. These molecules can therefore serve as lead molecules for further development of powerful TSH agonists. C1 [Latif, Rauf; Ali, M. Rejwan; Ma, Risheng; David, Martine; Morshed, Syed A.; Davies, Terry F.] Icahn Sch Med Mt Sinai, Dept Med, Thyroid Res Unit, New York, NY 10029 USA. [Latif, Rauf; Ali, M. Rejwan; Ma, Risheng; David, Martine; Morshed, Syed A.; Davies, Terry F.] James J Peters VAMC, New York, NY 10468 USA. [Ohlmeyer, Michael; Mezei, Mihaly] Icahn Sch Med Mt Sinai, Dept Struct & Chem Biol, New York, NY 10029 USA. [Felsenfeld, Dan P.; Lau, Zerlina] Icahn Sch Med Mt Sinai, Expt Therapeut Inst, Integrated Screening Core, New York, NY 10029 USA. RP Latif, R (reprint author), James J Peters VAMC, Room 2F-30,130 West Kingsbridge Rd, New York, NY 10468 USA. EM rauf.latif@mssm.edu FU NIH [DK069713, DK052464]; VA Merit Award program FX This work was supported in part by NIH grants DK069713, DK052464, and the VA Merit Award program (to T.F.D.). NR 58 TC 7 Z9 8 U1 0 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD JAN 1 PY 2015 VL 25 IS 1 BP 51 EP 62 DI 10.1089/thy.2014.0119 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AY4GP UT WOS:000347536600007 PM 25333622 ER PT J AU Sun, R Celli, A Crumrine, D Hupe, M Adame, LC Pennypacker, SD Park, K Uchida, Y Feingold, KR Elias, PM Ilic, D Mauro, TM AF Sun, Richard Celli, Anna Crumrine, Debra Hupe, Melanie Adame, Lillian C. Pennypacker, Sally D. Park, Kyungho Uchida, Yoshikazu Feingold, Kenneth R. Elias, Peter M. Ilic, Dusko Mauro, Theodora M. TI Lowered Humidity Produces Human Epidermal Equivalents with Enhanced Barrier Properties SO TISSUE ENGINEERING PART C-METHODS LA English DT Article ID RECONSTRUCTED HUMAN EPIDERMIS; HUMAN SKIN EQUIVALENTS; AIR-LIQUID INTERFACE; STRATUM-CORNEUM; PERMEABILITY BARRIER; HUMAN KERATINOCYTES; IN-VITRO; CALCIUM GRADIENT; ANTIMICROBIAL PEPTIDE; TIGHT JUNCTIONS AB Multilayered human keratinocyte cultures increasingly are used to model human epidermis. Until now, studies utilizing human epidermal equivalents (HEEs) have been limited because previous preparations do not establish a normal epidermal permeability barrier. In this report, we show that reducing environmental humidity to 50% relative humidity yields HEEs that closely match human postnatal epidermis and have enhanced repair of the permeability barrier. These cultures display low transepidermal water loss and possess a calcium and pH gradient that resembles those seen in human epidermis. These cultures upregulate glucosylceramide synthase and make normal-appearing lipid lamellar bilayers. The epidermal permeability barrier of these cultures can be perturbed, using the identical tools previously described for human skin, and recover in the same time course seen during in vivo barrier recovery. These cultures will be useful for basic and applied studies on epidermal barrier function. C1 [Sun, Richard; Celli, Anna; Crumrine, Debra; Hupe, Melanie; Adame, Lillian C.; Pennypacker, Sally D.; Park, Kyungho; Uchida, Yoshikazu; Elias, Peter M.; Mauro, Theodora M.] San Francisco Vet Adm Med Ctr, Dept Dermatol, San Francisco, CA 94158 USA. [Celli, Anna; Crumrine, Debra; Hupe, Melanie; Pennypacker, Sally D.; Uchida, Yoshikazu; Elias, Peter M.; Mauro, Theodora M.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Feingold, Kenneth R.] San Francisco Vet Adm Med Ctr, Metab Unit, San Francisco, CA 94158 USA. [Ilic, Dusko] Kings Coll London, Womens Hlth Acad Ctr, Div Womens Hlth, Stem Cell Lab,Assisted Concept Unit, London WC2R 2LS, England. RP Mauro, TM (reprint author), San Francisco Vet Adm Med Ctr, Dept Dermatol, 1700 Owens,Rm 338, San Francisco, CA 94158 USA. EM maurot@derm.ucsf.edu FU NIH [R21 ARO61583, R01 AR051930, AR062025]; Research Service, Department of Veterans Affairs FX The authors gratefully acknowledge the superb editorial assistance of Ms. Joan Wakefield, Ms. Jerelyn Magnusson, and Dr. Mathias Sulk. This work was supported by NIH grants R21 ARO61583 and R01 AR051930 (T.M.M.) and AR062025 (Y.U.) and the Research Service, Department of Veterans Affairs. NR 53 TC 8 Z9 9 U1 1 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3384 EI 1937-3392 J9 TISSUE ENG PART C-ME JI Tissue Eng. Part C-Methods PD JAN 1 PY 2015 VL 21 IS 1 BP 15 EP 22 DI 10.1089/ten.tec.2014.0065 PG 8 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA AY4HI UT WOS:000347538400002 PM 24803151 ER PT J AU Dempsey, J Regan, S Drehmer, JE Finch, S Hipple, B Klein, JD Murphy, S Nabi-Burza, E Ossip, D Woo, H Winickoff, JP AF Dempsey, Janelle Regan, Susan Drehmer, Jeremy E. Finch, Stacia Hipple, Bethany Klein, Jonathan D. Murphy, Sybil Nabi-Burza, Emara Ossip, Deborah Woo, Heide Winickoff, Jonathan P. TI Black Versus White Differences in Rates of Addressing Parental Tobacco Use in the Pediatric Setting SO ACADEMIC PEDIATRICS LA English DT Article DE pediatrics; racial differences; smoking cessation; tobacco control; tobacco smoke ID SMOKING-CESSATION INTERVENTIONS; HEALTH-CARE PROVIDERS; RACIAL/ETHNIC DISPARITIES; ETHNIC DISPARITIES; SECONDHAND SMOKE; PRENATAL-CARE; UNITED-STATES; ADVICE; CHILDREN; METAANALYSIS AB OBJECTIVE: To examine racial differences in rates of screening parents for cigarette smoking during pediatric outpatient visits and to determine if a parental tobacco control intervention mitigates racial variation in whether cigarette smoking is addressed. METHODS: As part of the Clinical Effort Against Secondhand Smoke Exposure (CEASE) randomized controlled trial, exit interviews were conducted with parents at 10 control and 10 intervention pediatric practices nationally. Parents were asked to report if during the visit did anyone ask if they smoke cigarettes. A generalized linear mixed model was used to estimate the effect of black vs white race on asking parents about cigarette smoking. RESULTS: Among 17,692 parents screened at the exit interview, the proportion of black parents who were current smokers (16%) was lower than the proportion of white parents who smoked (20%) (P < .001). In control group practices, black parents were more likely to be asked (adjusted risk ratio 1.23; 95% confidence interval 1.08, 1.40) about cigarette smoking by pediatricians than whites. In intervention group practices both black and white parents were more likely to be asked about smoking than those in control practices and there was no significant difference between black and white parents in the likelihood of being asked (adjusted risk ratio 1.01; 95% confidence interval 0.93, 1.09). CONCLUSIONS: Although a smaller proportion of black parents in control practices smoked than white, black parents were more likely to be asked by pediatricians about smoking. The CEASE intervention was associated with higher levels of screening for smoking for both black and white parents. C1 [Dempsey, Janelle; Drehmer, Jeremy E.; Hipple, Bethany; Murphy, Sybil; Nabi-Burza, Emara; Winickoff, Jonathan P.] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Res & Policy, Boston, MA 02114 USA. [Dempsey, Janelle; Drehmer, Jeremy E.; Hipple, Bethany; Murphy, Sybil; Nabi-Burza, Emara; Winickoff, Jonathan P.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Regan, Susan] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Finch, Stacia] Amer Acad Pediat, Pediat Res Off Settings, Elk Grove Village, IL USA. [Klein, Jonathan D.; Winickoff, Jonathan P.] Amer Acad Pediat, AAP Richmond Ctr Excellence, Elk Grove Village, IL USA. [Ossip, Deborah] Univ Rochester, Dept Publ Hlth Sci, Rochester, NY USA. [Woo, Heide] Univ Calif Los Angeles, West Los Angeles Off, Los Angeles, CA USA. RP Winickoff, JP (reprint author), Massachusetts Gen Hosp Children, Ctr Child & Adolescent Hlth Res & Policy, 100 Cambridge St,15th Floor,Suite 1542A, Boston, MA 02114 USA. EM jwinickoff@mgh.harvard.edu FU National Institutes of Health [R01-CA 127127]; National Institute on Drug Abuse; Agency for Healthcare Research and Quality; Flight Attendant Medical Research Institute; Pediatric Research in Office Settings (PROS) Network; HRSA MCHB [HRSA 5-UA6-10-001] FX This study was supported by the National Institutes of Health grant R01-CA 127127 (to Dr Winickoff), National Institute on Drug Abuse, and the Agency for Healthcare Research and Quality. This study was also partially supported by a grant from the Flight Attendant Medical Research Institute to the AAP Julius B. Richmond Center, and the Pediatric Research in Office Settings (PROS) Network, which receives core funding from the HRSA MCHB (HRSA 5-UA6-10-001) and the AAP. NR 43 TC 0 Z9 0 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 EI 1876-2867 J9 ACAD PEDIATR JI Acad. Pediatr. PD JAN-FEB PY 2015 VL 15 IS 1 BP 47 EP 53 PG 7 WC Pediatrics SC Pediatrics GA AY0BJ UT WOS:000347262600008 PM 25528125 ER PT J AU Macias, CG Mansbach, JM Fisher, ES Riederer, M Piedra, PA Sullivan, AF Espinola, JA Camargo, CA AF Macias, Charles G. Mansbach, Jonathan M. Fisher, Erin S. Riederer, Mark Piedra, Pedro A. Sullivan, Ashley F. Espinola, Janice A. Camargo, Carlos A., Jr. TI Variability in Inpatient Management of Children Hospitalized With Bronchiolitis SO ACADEMIC PEDIATRICS LA English DT Article DE bronchiolitis; intraclass correlation coefficient; hospitalization; quality of care; variation ID LENGTH-OF-STAY; PROSPECTIVE-MULTICENTER; EMERGENCY-DEPARTMENT; GUIDELINE IMPLEMENTATION; RESOURCE UTILIZATION; CLINICAL PATHWAY; UNITED-STATES; CARE; IMPACT; METAANALYSIS AB OBJECTIVE: To determine the variability between hospitals in diagnostic testing and management interventions for children with bronchiolitis admitted to inpatient wards and identify its association with patient characteristics. METHODS: A prospective, multicenter (16 hospitals), multi-year (2007-2010) observational study of children (age <2 years) hospitalized with bronchiolitis. Outcomes included variability in diagnostic testing (complete blood count, chest radiographs) and medications or interventions (bronchodilator, systemic corticosteroid, antibiotic, IV placement) by hospital. A modified Respiratory Distress Severity Score was utilized to assess severity of illness. For all outcomes, intraclass correlation coefficient (ICC) was calculated from a model to estimate the random effects of hospital without added covariates and compared to ICCs from a second model that adjusted for demographic and clinical patient characteristics. A second unadjusted and adjusted model was created for age >= 2 months. RESULTS: Of 2207 subjects, 1715 were identified as admitted to inpatient wards. We observed wide variations in the proportion of patients who received diagnostic testing (complete blood count 21-75%, chest radiograph 36-85%) and medications/interventions (bronchodilators 19-91%, systemic corticosteroids 8-44%, antibiotics 17-43%, IV placement 38-93%). Adjusting for demographic and clinical patient characteristics did not materially affect the proportion of variability attributable to hospitals (differences in ICCs with and without model adjustment <4%). CONCLUSIONS: Wide variations in diagnostic test utilization and management interventions seen among children with bronchiolitis treated on the inpatient wards at 16 US hospitals were not attributable to demographic or clinical patient characteristics. These results further support efforts to standardize care for bronchiolitis through active quality improvement strategies. C1 [Macias, Charles G.] Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, Sect Emergency Med, Houston, TX 77030 USA. [Macias, Charles G.] Texas Childrens Hosp, Baylor Coll Med, Ctr Clin Effectiveness, Houston, TX 77030 USA. [Mansbach, Jonathan M.] Harvard Univ, Sch Med, Dept Med, Childrens Hosp Boston, Boston, MA USA. [Fisher, Erin S.] Univ Calif San Diego, Dept Pediat, Rady Childrens Hosp, San Diego, CA 92103 USA. [Riederer, Mark] Childrens Hosp Colorado, Dept Pediat, Denver, CO USA. [Piedra, Pedro A.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Piedra, Pedro A.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Sullivan, Ashley F.; Espinola, Janice A.; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Macias, CG (reprint author), 6621 Fannin St,Suite A2210, Houston, TX 77030 USA. EM cgmacias@texaschildrens.org FU National Institutes of Health (Bethesda, MD) [U01 AI-67693, K23 AI-77801] FX This study was supported by the grants U01 AI-67693 and K23 AI-77801 from the National Institutes of Health (Bethesda, MD). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. We thank the Multicenter Airway Research Collaboration-30 investigators for their ongoing dedication to bronchiolitis research. No conflicts of interest regarding this work have been reported by any of the investigators. NR 37 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 EI 1876-2867 J9 ACAD PEDIATR JI Acad. Pediatr. PD JAN-FEB PY 2015 VL 15 IS 1 BP 69 EP 76 PG 8 WC Pediatrics SC Pediatrics GA AY0BJ UT WOS:000347262600011 PM 25444654 ER PT J AU Hasegawa, K Pate, BM Mansbach, JM Macias, CG Fisher, ES Piedra, PA Espinola, JA Sullivan, AF Camargo, CA AF Hasegawa, Kohei Pate, Brian M. Mansbach, Jonathan M. Macias, Charles G. Fisher, Erin S. Piedra, Pedro A. Espinola, Janice A. Sullivan, Ashley F. Camargo, Carlos A., Jr. TI Risk Factors for Requiring Intensive Care Among Children Admitted to Ward With Bronchiolitis SO ACADEMIC PEDIATRICS LA English DT Article DE bronchiolitis; hospitalization; intensive care unit; mechanical ventilation; risk factors ID REAL-TIME PCR; PROSPECTIVE MULTICENTER; MANAGEMENT; INFECTION; DIAGNOSIS; OUTCOMES; LEVEL AB OBJECTIVE: To examine risk factors for transfer of bronchiolitis patients from the ward to the intensive care unit (ICU) and/or initiation of critical care interventions. METHODS: We performed a 16-center, prospective cohort study of hospitalized children age <2 years with bronchiolitis. During the winters of 2007 to 2010, researchers collected clinical data and nasopharyngeal aspirates from study participants. The primary outcome was late intensive care use, defined as a transfer to the ICU and/or use of mechanical ventilation (regardless of location) after the child's first inpatient day. RESULTS: Among 2104 children hospitalized with bronchiolitis, 1762 (84%) were identified as initial ward patients, comprising the analysis cohort. The median age was 4 months (interquartile range, 2-9 months), and 1048 (59%) were boys. The most frequently detected pathogens were respiratory syncytial virus (72%) and rhinovirus (25%). After the first inpatient day, 47 (3%; 95% confidence interval, 2-4) were subsequently transferred to the ICU or required mechanical ventilation. In the multivariable logistic regression model predicting subsequent transfer to the ICU or mechanical ventilation use, the significant predictors were birth weight <5 pounds (odds ratio, 2.28; 95% confidence interval, 1.30-4.02; P = .004) and respiratory rate high of >= 70 breaths/min on the first inpatient day (odds ratio, 4.64; 95% confidence interval, 2.86-7.53; P < .001). CONCLUSIONS: In this multicenter study of children hospitalized with bronchiolitis, low birth weight and tachypnea were significantly associated with subsequent transfer to the ICU and/or use of mechanical ventilation. C1 [Hasegawa, Kohei; Espinola, Janice A.; Sullivan, Ashley F.; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Pate, Brian M.] Childrens Mercy Hosp, Dept Pediat, Kansas City, MO 64108 USA. [Mansbach, Jonathan M.] Harvard Univ, Sch Med, Dept Med, Boston Childrens Hosp, Boston, MA USA. [Macias, Charles G.] Texas Childrens Hosp, Baylor Coll Med, Sect Emergency Med, Dept Pediat, Houston, TX 77030 USA. [Fisher, Erin S.] Univ Calif San Diego, Dept Pediat, Rady Childrens Hosp, San Diego, CA 92103 USA. [Piedra, Pedro A.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Piedra, Pedro A.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. RP Hasegawa, K (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM khasegawa1@partners.org FU National Institutes of Health (Bethesda, Md) [U01 AI-67693, K23 AI-77801] FX This study was supported by grants U01 AI-67693 and K23 AI-77801 from the National Institutes of Health (Bethesda, Md). The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. We thank the MARC-30 investigators, listed below, for their ongoing dedication to bronchiolitis research. We also thank Ashley F. Sullivan, MPH, MS (Emergency Medicine Network, Massachusetts General Hospital, Boston, Mass), for her administrative and logistical support. NR 19 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 EI 1876-2867 J9 ACAD PEDIATR JI Acad. Pediatr. PD JAN-FEB PY 2015 VL 15 IS 1 BP 77 EP 81 DI 10.1016/j.acap.2014.06.008 PG 5 WC Pediatrics SC Pediatrics GA AY0BJ UT WOS:000347262600012 PM 25528126 ER PT J AU Lahav, A AF Lahav, Amir TI Questionable sound exposure outside of the womb: frequency analysis of environmental noise in the neonatal intensive care unit SO ACTA PAEDIATRICA LA English DT Article DE Environment; Frequency; NICU; Noise; Preterm infants ID PRETERM INFANTS; SPEECH; DISCRIMINATION; EXPERIENCE; SPACE; ICU AB Aim: Recent research raises concerns about the adverse effects of noise exposure on the developing preterm infant. However, current guidelines for NICU noise remain focused on loudness levels, leaving the problem of exposure to potentially harmful sound frequencies largely overlooked. This study examined the frequency spectra present in a level-II NICU. Methods: Noise measurements were taken in two level-II open-bay nurseries. Measurements were taken over 5 days for a period of 24 h each. Spectral analysis was focused on comparing sound frequencies in the range of human speech during daytime (7 AM-7 PM) vs. night-time (7 PM-7 AM). Results: On average, daytime noise levels (L-eq = 60.05 dBA) were higher than night-time (L-eq = 58.67 dBA). Spectral analysis of frequency bands (>50 dB) revealed that infants were exposed to frequencies <500 Hz 100% of the time and to frequencies >500 Hz 57% of the time. During daytime, infants were exposed to nearly 20% more sounds within the speech frequency range compared with night-time (p = 0.018). Conclusion: Measuring the frequency spectra of NICU sounds is necessary to attain a thorough understanding of both the noise levels and the type of sounds that preterm infants are exposed to throughout their hospital stay. The risk of high-frequency noise exposure in the preterm population is still unclear and warrants further investigation. C1 [Lahav, Amir] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pediat & Newborn Med, Boston, MA 02115 USA. [Lahav, Amir] Harvard Univ, Sch Med, Dept Pediat, MassGen Hosp Children, Boston, MA 02115 USA. RP Lahav, A (reprint author), Brigham & Womens Hosp, Dept Newborn Med, 75 Francis St, Boston, MA 02115 USA. EM amir_lahav@hms.harvard.edu FU Charles H. Hood Foundation; Peter and Elizabeth C. Tower Foundation; Gerber Foundation; Little Giraffe Foundation; Nexxspan Healthcare FX We thank Emily Zimmerman for assisting with the execution of the study and the preparation of this manuscript. We thank Brian Arnold for helping with data collection. This work was supported in part by the Charles H. Hood Foundation, Peter and Elizabeth C. Tower Foundation, Gerber Foundation, Little Giraffe Foundation and Nexxspan Healthcare. NR 30 TC 3 Z9 3 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0803-5253 EI 1651-2227 J9 ACTA PAEDIATR JI Acta Paediatr. PD JAN PY 2015 VL 104 IS 1 BP E14 EP E19 DI 10.1111/apa.12816 PG 6 WC Pediatrics SC Pediatrics GA AX5SJ UT WOS:000346987300003 PM 25264140 ER PT J AU Schackman, BR Leff, JA Barter, DM DiLorenzo, MA Feaster, DJ Metsch, LR Freedberg, KA Linas, BP AF Schackman, Bruce R. Leff, Jared A. Barter, Devra M. DiLorenzo, Madeline A. Feaster, Daniel J. Metsch, Lisa R. Freedberg, Kenneth A. Linas, Benjamin P. TI Cost-effectiveness of rapid hepatitis C virus (HCV) testing and simultaneous rapid HCV and HIV testing in substance abuse treatment programs SO ADDICTION LA English DT Review DE Computer simulation model; cost-effectiveness; economic evaluation; hepatitis C testing; rapid HIV testing; substance abuse treatment ID SUSTAINED VIROLOGICAL RESPONSE; QUALITY-OF-LIFE; INJECTION-DRUG USERS; INTERFERON-ALPHA-2B PLUS RIBAVIRIN; HEALTH-STATE UTILITIES; HIGH-RISK POPULATIONS; UNITED-STATES; RANDOMIZED-TRIAL; COINFECTED PATIENTS; FOLLOW-UP AB AimsTo evaluate the cost-effectiveness of rapid hepatitis C virus (HCV) and simultaneous HCV/HIV antibody testing in substance abuse treatment programs. DesignWe used a decision analytic model to compare the cost-effectiveness of no HCV testing referral or offer, off-site HCV testing referral, on-site rapid HCV testing offer and on-site rapid HCV and HIV testing offer. Base case inputs included 11% undetected chronic HCV, 0.4% undetected HIV, 35% HCV co-infection among HIV-infected, 53% linked to HCV care after testing antibody-positive and 67% linked to HIV care. Disease outcomes were estimated from established computer simulation models of HCV [Hepatitis C Cost-Effectiveness (HEP-CE)] and HIV [Cost-Effectiveness of Preventing AIDS Complications (CEPAC)]. Setting and participantsData on test acceptance and costs were from a national randomized trial of HIV testing strategies conducted at 12 substance abuse treatment programs in the United States. MeasurementsLifetime costs (2011 US$) and quality-adjusted life years (QALYs) discounted at 3% annually; incremental cost-effectiveness ratios (ICERs). FindingsOn-site rapid HCV testing had an ICER of $18300/QALY compared with no testing, and was more efficient than (dominated) off-site HCV testing referral. On-site rapid HCV and HIV testing had an ICER of $64500/QALY compared with on-site rapid HCV testing alone. In one- and two-way sensitivity analyses, the ICER of on-site rapid HCV and HIV testing remained <$100000/QALY, except when undetected HIV prevalence was <0.1% or when we assumed frequent HIV testing elsewhere. The ICER remained <$100000/QALY in 91% of probabilistic sensitivity analyses. ConclusionsOn-site rapid hepatitis C virus and HIV testing in substance abuse treatment programs is cost-effective at a <$100000/quality-adjusted life year threshold. C1 [Schackman, Bruce R.; Leff, Jared A.] Weill Cornell Med Coll, Dept Healthcare Policy & Res, New York, NY 10065 USA. [Barter, Devra M.; Linas, Benjamin P.] Boston Med Ctr, Infect Dis Sect, Dept Med, HIV Epidemiol & Outcomes Res Unit, Boston, MA USA. [DiLorenzo, Madeline A.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [DiLorenzo, Madeline A.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Feaster, Daniel J.; Metsch, Lisa R.] Univ Miami, Miller Sch Med, Dept Publ Hlth Sci, Miami, FL 33136 USA. [Metsch, Lisa R.] Columbia Univ, Mailman Sch Publ Hlth, Dept Sociomed Sci, New York, NY USA. [Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Freedberg, Kenneth A.; Linas, Benjamin P.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Schackman, BR (reprint author), Weill Cornell Med Coll, Dept Healthcare Policy & Res, 425 East 61st St,Suite 301, New York, NY 10065 USA. EM brs2006@med.cornell.edu OI Leff, Jared/0000-0001-6995-6009 FU National Institute on Drug Abuse [R01DA031059, R01DA027379]; National Institute of Allergy and Infectious Diseases [R37AI042006]; National Drug Abuse Treatment Clinical Trials Network (CTN) [U10 DA013720, U10DA13720-09S, U10 DA020036, U10DA15815, U10DA13034, U10DA013038, U10 DA013732, U10 DA13036, U10 DA13727, U10DA015833, HHSN271200522081C, HHSN271200522071C] FX The authors gratefully acknowledge Marion Robine, Melanie Gaynes and Jake Roberts Morgan for research assistance and the members of the Using Modeling to Inform Public Health (UMPH!) seminar at Yale University School of Medicine for their valuable comments on preliminary research findings. Parts of this paper were presented at the 35th Annual Meeting of the Society for Medical Decision Making in Baltimore, MD, 21-23 October 2013. This study was funded by the National Institute on Drug Abuse (R01DA031059, R01DA027379), the National Institute of Allergy and Infectious Diseases (R37AI042006) and the National Drug Abuse Treatment Clinical Trials Network (CTN) (U10 DA013720, U10DA13720-09S, U10 DA020036, U10DA15815, U10DA13034, U10DA013038, U10 DA013732, U10 DA13036, U10 DA13727, U10DA015833, HHSN271200522081C, HHSN271200522071C). The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies or the US government. NR 112 TC 10 Z9 10 U1 3 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0965-2140 EI 1360-0443 J9 ADDICTION JI Addiction PD JAN PY 2015 VL 110 IS 1 BP 129 EP 143 DI 10.1111/add.12754 PG 15 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AX1IA UT WOS:000346699700021 PM 25291977 ER PT J AU Jain, S Oldenburg, CE Mimiaga, MJ Mayer, KH AF Jain, Sachin Oldenburg, Catherine E. Mimiaga, Matthew J. Mayer, Kenneth H. TI Subsequent HIV Infection Among Men Who Have Sex with Men Who Used Non-Occupational Post-Exposure Prophylaxis at a Boston Community Health Center: 1997-2013 SO AIDS PATIENT CARE AND STDS LA English DT Article ID RISK BEHAVIOR; CONFOUNDER-SELECTION; HOMOSEXUAL-MEN; TENOFOVIR DF; LATINO MEN; EXPOSURE; SEROCONVERSION; EMTRICITABINE; EPIDEMIOLOGY; TRANSMISSION AB Non-occupational post-exposure prophylaxis (NPEP) has been recommended to prevent HIV acquisition for nearly 20 years. However, limited behavioral and clinical outcome data exist after men who have sex with men (MSM) present for NPEP. We reviewed the electronic medical records of HIV-uninfected adults who presented for NPEP at a large community health center in Boston between July, 1997 and August, 2013. Data from 894 patients were analyzed, 88.1% of whom were MSM. Consensual unprotected sex was the most common reason for NPEP visits among MSM (64.2%), followed by condom failure (30.6%). The HIV serostatus of the partner was unknown for 64.4% of the MSM, positive with unknown treatment status for 18.1%, positive and not on treatment for 4.1%, and positive and on treatment for 13.4%. Thirty-nine patients subsequently became HIV-infected (4.4%), all of whom were MSM. The MSM-specific HIV incidence after NPEP use was 2.2 cases per 100 person-years. Incident HIV infection was associated with younger age (AHR=0.94; p=0.003), being Latino (AHR=2.44; p=0.044), and/or being African American (AHR=3.43; p=0.046). Repeated NPEP use was not associated with incident HIV infection (AHR=0.67; p=0.26). Younger MSM of color who access NPEP, in particular, may benefit from early HIV risk-reduction and pre-exposure prophylaxis counseling. C1 [Jain, Sachin; Mayer, Kenneth H.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. [Jain, Sachin; Oldenburg, Catherine E.; Mimiaga, Matthew J.; Mayer, Kenneth H.] Fenway Inst, Boston, MA USA. [Oldenburg, Catherine E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Jain, Sachin; Mayer, Kenneth H.] Harvard Univ, Sch Med, Boston, MA USA. [Mimiaga, Matthew J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Jain, S (reprint author), AIDS Ctr, Montefiore Med Ctr, 3444 Kossuth Ave, Bronx, NY 10467 USA. EM sajain@montefiore.org FU Harvard University Center For AIDS Research (CFAR), an NIH [P30 AI060354]; National Institute of Allergy and Infectious Disease T32 NRSA grant [T32AI007535]; National Institute of Drug Abuse T32 NRSA grant [T32DA0131911] FX The Fenway Institute Data Team, including Chris Grasso MPH, Ken Levine, and Shayne Zaslow, screened eligible patients for this study, aided with construction of the data abstraction tool, and provided database support. The Harvard University Center For AIDS Research (CFAR), an NIH funded program (P30 AI060354; PI: Walker), provided statistical consultation and contributes to Mayer's funding. Oldenburg is supported by a National Institute of Allergy and Infectious Disease T32 NRSA grant (T32AI007535; PI: Seage) and a National Institute of Drug Abuse T32 NRSA grant (T32DA0131911; PI: Flanigan). NR 31 TC 9 Z9 9 U1 0 U2 8 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 EI 1557-7449 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD JAN 1 PY 2015 VL 29 IS 1 BP 20 EP 25 DI 10.1089/apc.2014.0154 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AY0MI UT WOS:000347290100004 PM 25369451 ER PT J AU Virani, SS Woodard, LD Ramsey, DJ Urech, TH Akeroyd, JM Shah, T Deswal, A Bozkurt, B Ballantyne, CM Petersen, LA AF Virani, Salim S. Woodard, LeChauncy D. Ramsey, David J. Urech, Tracy H. Akeroyd, Julia M. Shah, Tina Deswal, Anita Bozkurt, Biykem Ballantyne, Christie M. Petersen, Laura A. TI Gender Disparities in Evidence-Based Statin Therapy in Patients With Cardiovascular Disease SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID DENSITY-LIPOPROTEIN; PRIMARY PREVENTION; CHOLESTEROL LEVELS; CONTROLLED-TRIAL; GOAL ATTAINMENT; DIABETES CARE; SIMVASTATIN; WOMEN; ATORVASTATIN; METAANALYSIS AB Studies have shown gender disparities in cholesterol care in patients with cardiovascular disease (CVD), with women less likely than men to have low-density lipoprotein cholesterol levels <100 mg/dl. Whether this is related to a lower evidence-based statin or high-intensity statin use is not known. We used a national cohort of 972,532 patients with CVD (coronary heart disease, peripheral artery disease, and ischemic stroke) receiving care in 130 Veterans Health Administration facilities from October 1, 2010, to September 30, 2011, to identify the proportion of male and female patients with CVD receiving any statin and high-intensity statin. Women with CVD (n = 13,371) were less likely than men to receive statins (57.6% vs 64.8%, p <0.0001) or high-intensity statins (21.1% vs 23.6%, p <0.0001). Mean low-density lipoprotein cholesterol levels (99 vs 85 mg/dl) were higher in women compared with men (p <0.0001). In adjusted models, female gender was independently associated with a lower likelihood of receiving statins (odds ratio 0.68, 95% confidence interval 0.66 to 0.71) or high-intensity statins (odds ratio 0.76, 95% confidence interval 0.73 to 0.80). The median facility-level rate of statin and high-intensity statin use among female patients (57.3% [interquartile range = 8.93%] for statin, 20% [interquartile range = 7.7%] for high-intensity statin use) showed significant variation. In conclusion, women with CVD are less likely to receive evidence-based statin and high-intensity statins compared with men, although, their use remains low in both genders. There is a significant facility-level variation in evidence-based statin or high-intensity statin use in female patients with CVD. With the "statin dose-based approach" proposed by the recent cholesterol guidelines, these results highlight areas for quality improvement. Published by Elsevier Inc. C1 [Virani, Salim S.; Woodard, LeChauncy D.; Ramsey, David J.; Urech, Tracy H.; Akeroyd, Julia M.; Petersen, Laura A.] Hlth Serv Res & Dev Ctr Innovat, Michael E DeBakey Vet Affairs Med Ctr, Hlth Policy Qual & Informat Program, Houston, TX 77030 USA. [Virani, Salim S.; Shah, Tina; Deswal, Anita; Bozkurt, Biykem] Michael E DeBakey VA Med Ctr, Cardiol Sect, Houston, TX USA. [Virani, Salim S.; Shah, Tina; Deswal, Anita; Bozkurt, Biykem; Ballantyne, Christie M.] Baylor Coll Med, Dept Med, Cardiol Sect, Houston, TX 77030 USA. [Virani, Salim S.; Ballantyne, Christie M.] Methodist DeBakey Heart & Vasc Ctr, Ctr Cardiovasc Dis Prevent, Houston, TX USA. RP Virani, SS (reprint author), Hlth Serv Res & Dev Ctr Innovat, Michael E DeBakey Vet Affairs Med Ctr, Hlth Policy Qual & Informat Program, Houston, TX 77030 USA. EM virani@bcm.edu OI Virani, Salim/0000-0001-9541-6954 FU Houston Veterans Affairs Health Services Research and Development Center for Innovations grant [HFP 90-020] FX This work was also supported by the Houston Veterans Affairs Health Services Research and Development Center for Innovations grant (grant HFP 90-020). The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 19 TC 24 Z9 25 U1 0 U2 9 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 JAN 1 PY 2015 VL 115 IS 1 BP 21 EP 26 DI 10.1016/j.amjcard.2014.09.041 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AY0HP UT WOS:000347278300004 PM 25456865 ER PT J AU Ashburner, JM Go, AS Reynolds, K Chang, Y Fang, MC Fredman, L Applebaum, KM Singer, DE AF Ashburner, Jeffrey M. Go, Alan S. Reynolds, Kristi Chang, Yuchiao Fang, Margaret C. Fredman, Lisa Applebaum, Katie M. Singer, Daniel E. TI Comparison of Frequency and Outcome of Major Gastrointestinal Hemorrhage in Patients With Atrial Fibrillation on Versus Not Receiving Warfarin Therapy (from the ATRIA and ATRIA-CVRN Cohorts) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID NET CLINICAL BENEFIT; INTRACEREBRAL HEMORRHAGE; INTRACRANIAL HEMORRHAGE; ANTICOAGULATION THERAPY; ANTITHROMBOTIC THERAPY; RANDOMIZED-TRIALS; RISK-FACTORS; STROKE; THROMBOEMBOLISM; PRESCRIPTION AB To date, there have been few studies evaluating outcomes of patients with atrial fibrillation (AF) who have experienced gastrointestinal (GI) hemorrhages. We examined short- and long-term mortality of major GI hemorrhage in patients with AF on and off warfarin in recent clinical care. We evaluated this association in the large Anticoagulation and Risk Factors in Atrial fibrillation (ATRIA) and ATRIA-Cardiovascular Research Network (CVRN) California community-based cohorts of patients with AF (study years 1996 to 2003 and 2006 to 2009, respectively), where all events were clinician adjudicated. We used proportional hazards regression with propensity score adjustment to estimate the short- (30 days) and long-term (>30 days for 1 year) mortality rate ratio for patients using warfarin compared with those who were not using warfarin at the time of GI hemorrhage. In the 414 ATRIA participants with major GI hemorrhage, 54% were taking warfarin at the time of the hemorrhage; in the 361 ATRIA-CVRN participants with major GI hemorrhage, 58% were taking warfarin. Warfarin use at the time of GI hemorrhage was not associated with 30-day mortality in the ATRIA cohort but was associated with significantly reduced 30-day mortality in the ATRIA-CVRN cohort (adjusted mortality rate ratio [95% confidence interval], ATRIA 0.97 [0.54 to 1.74]; ATRIA-CVRN 0.38 [0.17 to 0.83]). There was a modest suggestion of lower mortality on warfarin after 30 days in both cohorts. In conclusion, our study demonstrates that GI hemorrhages on warfarin are certainly no worse and may be less life threatening than those occurring off warfarin. These findings are in stark contrast to the deleterious effect of warfarin on mortality from intracranial hemorrhage and add another factor favoring anticoagulation in clinical decision making for patients with AF. (C) 2015 Elsevier Inc. All rights reserved. C1 [Ashburner, Jeffrey M.; Chang, Yuchiao; Singer, Daniel E.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Ashburner, Jeffrey M.; Fredman, Lisa] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Go, Alan S.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Reynolds, Kristi] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA 91101 USA. [Fang, Margaret C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Applebaum, Katie M.] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Environm & Occupat Hlth, Washington, DC USA. [Applebaum, Katie M.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Ashburner, JM (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. EM jashburner@mgh.harvard.edu FU National Institute on Aging [R01 AG15478, K23 AG028978]; National Heart, Lung, and Blood Institute [U19 HL91179, RC2HL101589]; Eliot B. and Edith C. Shoolman fund of the Massachusetts General Hospital (Boston, MA) FX This study was supported by the National Institute on Aging (R01 AG15478 and K23 AG028978), the National Heart, Lung, and Blood Institute (U19 HL91179 and RC2HL101589), and the Eliot B. and Edith C. Shoolman fund of the Massachusetts General Hospital (Boston, MA). The funding sources had no role in study design, data collection, data analysis, data interpretation, or preparation of this article. Jeffrey Ashburner, MPH, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. NR 26 TC 3 Z9 3 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 1 PY 2015 VL 115 IS 1 BP 40 EP 46 DI 10.1016/j.amjcard.2014.10.006 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AY0HP UT WOS:000347278300007 PM 25456871 ER PT J AU Dashti, HS Follis, JL Smith, CE Tanaka, T Cade, BE Gottlieb, DJ Hruby, A Jacques, PF Lamon-Fava, S Richardson, K Saxena, R Scheer, FAJL Kovanen, L Bartz, TM Perala, MM Jonsson, A Frazier-Wood, AC Kalafati, IP Mikkila, V Partonen, T Lemaitre, RN Lahti, J Hernandez, DG Toft, U Johnson, WC Kanoni, S Raitakari, OT Perola, M Psaty, BM Ferrucci, L Grarup, N Highland, HM Rallidis, L Kahonen, M Havulinna, AS Siscovick, DS Raikkonen, K Jorgensen, T Rotter, JI Deloukas, P Viikari, JSA Mozaffarian, D Linneberg, A Seppala, I Hansen, T Salomaa, V Gharib, SA Eriksson, JG Bandinelli, S Pedersen, O Rich, SS Dedoussis, G Lehtimaki, T Ordovaas, JM AF Dashti, Hassan S. Follis, Jack L. Smith, Caren E. Tanaka, Toshiko Cade, Brian E. Gottlieb, Daniel J. Hruby, Adela Jacques, Paul F. Lamon-Fava, Stefania Richardson, Kris Saxena, Richa Scheer, Frank A. J. L. Kovanen, Leena Bartz, Traci M. Perala, Mia-Maria Jonsson, Anna Frazier-Wood, Alexis C. Kalafati, Ioanna-Panagiota Mikkila, Vera Partonen, Timo Lemaitre, Rozenn N. Lahti, Jari Hernandez, Dena G. Toft, Ulla Johnson, W. Craig Kanoni, Stavroula Raitakari, Olli T. Perola, Markus Psaty, Bruce M. Ferrucci, Luigi Grarup, Niels Highland, Heather M. Rallidis, Loukianos Kahonen, Mika Havulinna, Aki S. Siscovick, David S. Raikkonen, Katri Jorgensen, Torben Rotter, Jerome I. Deloukas, Panos Viikari, Jorma S. A. Mozaffarian, Dariush Linneberg, Allan Seppala, Ilkka Hansen, Torben Salomaa, Veikko Gharib, Sina A. Eriksson, Johan G. Bandinelli, Stefania Pedersen, Oluf Rich, Stephen S. Dedoussis, George Lehtimaki, Terho Ordovas, Jose M. TI Habitual sleep duration is associated with BMI and macronutrient intake and may be modified by CLOCK genetic variants SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE CLOCK; circadian rhythm; dietary intake; gene-environment interaction; sleep duration ID FOOD-FREQUENCY QUESTIONNAIRE; BODY-MASS INDEX; ENERGY-EXPENDITURE; METABOLIC SYNDROME; METAANALYSIS; ADULTS; OBESITY; SEX; CURTAILMENT; POPULATION AB Background: Short sleep duration has been associated with greater risks of obesity, hypertension, diabetes, and cardiovascular disease. Also, common genetic variants in the human Circadian Locomotor Output Cycles Kaput (CLOCK) show associations with ghrelin and total energy intake. Objectives: We examined associations between habitual sleep duration, body mass index (BM), and macronutrient intake and assessed whether CLOCK variants modify these associations. Design: We conducted inverse-variance weighted, fixed-effect meta-analyses of results of adjusted associations of sleep duration and BMI and macronutrient intake as percentages of total energy as well as interactions with CLOCK variants from 9 cohort studies including up to 14,906 participants of European descent from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Results: We observed a significant association between sleep duration and lower BMI (beta +/- SE = 0.16 +/- 0.04, P < 0.0001) in the overall sample; however, associations between sleep duration and relative macronutrient intake were evident in age- and sex-stratified analyses only. We observed a significant association between sleep duration and lower saturated fatty acid intake in younger (aged 20-64 y) adults (men: 0.11 +/- 0.06%, P = 0.03; women: 0.10 +/- 0.05%, P = 0.04) and with lower carbohydrate (-0.31 0.12%, P < 0.01), higher total fat (0.18 +/- 0.09%, P = 0.05), and higher PUFA (0.05 +/- 0.02%, P = 0.02) intakes in older (aged 65-80 y) women. In addition, the following 2 nominally significant interactions were observed: between sleep duration and rs12649507 on PUFA intake and between sleep duration and rs6858749 on protein intake. Conclusions: Our results indicate that longer habitual sleep duration is associated with lower BMI and age- and sex-specific favorable dietary behaviors. Differences in the relative intake of specific macronutrients associated with short sleep duration could, at least in part, explain previously reported associations between short sleep duration and chronic metabolic abnormalities. In addition, the influence of obesity-associated CLOCK variants on the association between sleep duration and macronutrient intake suggests that longer habitual sleep duration could ameliorate the genetic predisposition to obesity via a favorable dietary profile. C1 Tufts Univ, Jean Mayer USDA, Human Nutr Res Ctr Aging, Nutr & Genom Lab, Boston, MA 02111 USA. [Dashti, Hassan S.; Smith, Caren E.; Richardson, Kris; Ordovas, Jose M.] Tufts Univ, Jean Mayer USDA, Human Nutr Res Ctr Aging, Nutr & Genom Lab, Boston, MA 02111 USA. [Jacques, Paul F.] Tufts Univ, Jean Mayer USDA, Human Nutr Res Ctr Aging, Nutr Epidemiol Lab, Boston, MA 02111 USA. [Lamon-Fava, Stefania] Tufts Univ, Jean Mayer USDA, Human Nutr Res Ctr Aging, Cardiovasc Nutr Lab, Boston, MA 02111 USA. [Follis, Jack L.] Univ St Thomas, Dept Math Comp Sci & Cooperat Engn, Houston, TX 77006 USA. [Tanaka, Toshiko; Ferrucci, Luigi] NIH, Translat Gerontol Branch, Baltimore, MD USA. [Hernandez, Dena G.] NIH, Neurogenet Lab, Baltimore, MD USA. [Cade, Brian E.; Gottlieb, Daniel J.; Saxena, Richa; Scheer, Frank A. J. L.] Brigham & Womens Hosp, Div Sleep & Circadian Disorders, Boston, MA 02115 USA. [Mozaffarian, Dariush] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Mozaffarian, Dariush] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Cade, Brian E.; Gottlieb, Daniel J.; Scheer, Frank A. J. L.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. [Mozaffarian, Dariush] Harvard Univ, Sch Med, Div Cardiovasc Med, Boston, MA USA. [Mozaffarian, Dariush] Harvard Univ, Sch Med, Charming Div Network Med, Boston, MA USA. [Gottlieb, Daniel J.] VA Boston Healthcare Syst, Sleep Disorders Ctr, Boston, MA USA. [Hruby, Adela; Mozaffarian, Dariush] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Saxena, Richa] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Saxena, Richa] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Saxena, Richa] Harvard Univ, Sch Med, Boston, MA USA. [Kovanen, Leena; Partonen, Timo] Natl Inst Hlth & Welf, Dept Mental Hlth, Helsinki, Finland. [Kovanen, Leena; Partonen, Timo] Natl Inst Hlth & Welf, Dept Substance Abuse Serv, Helsinki, Finland. [Perala, Mia-Maria; Perola, Markus; Havulinna, Aki S.; Salomaa, Veikko; Eriksson, Johan G.] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Lehtimaki, Terho] Natl Inst Hlth & Welf, Helsinki, Finland. [Bartz, Traci M.; Lemaitre, Rozenn N.; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Bartz, Traci M.; Lemaitre, Rozenn N.; Psaty, Bruce M.; Gharib, Sina A.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Bartz, Traci M.; Johnson, W. Craig] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol & Hlth Serv, Seattle, WA 98195 USA. [Gharib, Sina A.] Univ Washington, Dept Computat Med, Seattle, WA 98195 USA. [Gharib, Sina A.] Univ Washington, Ctr Lung Biol, Seattle, WA 98195 USA. [Jonsson, Anna; Grarup, Niels; Hansen, Torben; Pedersen, Oluf] Univ Copenhagen, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark. [Linneberg, Allan] Univ Copenhagen, Dept Clin Med, Copenhagen, Denmark. Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark. [Frazier-Wood, Alexis C.] Baylor Coll Med, USDA ARS, Childrens Nutr Res Ctr, Dept Pediat, Houston, TX 77030 USA. [Kalafati, Ioanna-Panagiota; Dedoussis, George] Harokopio Univ, Dept Nutr & Dietet, Athens, Greece. [Mikkila, Vera] Univ Helsinki, Dept Food & Environm Sci, Div Nutr, Helsinki, Finland. [Lahti, Jari; Raikkonen, Katri] Univ Helsinki, Inst Behav Sci, Helsinki, Finland. [Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. [Lahti, Jari; Eriksson, Johan G.] Folkhalsan Res Ctr, Helsinki, Finland. [Toft, Ulla; Jorgensen, Torben] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark. [Linneberg, Allan] Glostrup Univ Hosp, Dept Clin Expt Res, Glostrup, Denmark. [Kanoni, Stavroula; Deloukas, Panos] William Harvey Res Inst, London, England. [Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Raitakari, Olli T.] Univ Turku, Dept Clin Physiol & Nucl Med, Turku, Finland. [Viikari, Jorma S. A.] Univ Turku, Dept Med, Turku, Finland. [Viikari, Jorma S. A.] Univ Turku, Div Med, Turku, Finland. [Viikari, Jorma S. A.] Turku Univ Hosp, FIN-20520 Turku, Finland. [Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth, Seattle, WA USA. [Highland, Heather M.] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Grad Sch Biomed Sci Houston, Sch Publ Hlth, Houston, TX 77030 USA. [Rallidis, Loukianos] Univ Gen Hosp, Dept Cardiol, Athens, Greece. [Kahonen, Mika] Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland. [Kahonen, Mika] Univ Tampere, FIN-33101 Tampere, Finland. [Siscovick, David S.] New York Acad Med, New York, NY USA. [Rotter, Jerome I.] Harbor Univ Calif, Los Angeles Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA USA. [Deloukas, Panos] King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah 21413, Saudi Arabia. [Seppala, Ilkka; Lehtimaki, Terho] Univ Tampere, Sch Med, Dept Clin Chem, Fimlab Labs, FIN-33101 Tampere, Finland. [Eriksson, Johan G.] Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland. [Eriksson, Johan G.] Vasa Cent Hosp, Vaasa, Finland. [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy. [Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Ordovas, Jose M.] Ctr Nacl Invest Cardiovasc, Dept Epidemiol, Madrid, Spain. [Ordovas, Jose M.] Inst Madrilefio Estudios Avanzados Alimentac, Madrid, Spain. RP Ordovaas, JM (reprint author), Tufts Univ, Jean Mayer USDA, Human Nutr Res Ctr Aging, Nutr & Genom Lab, 711 Washington St, Boston, MA 02111 USA. EM jose.ordovas@tufts.edu RI Grarup, Niels/K-2807-2015; Deloukas, Panos/B-2922-2013; Wood, Lekki/B-8053-2010; OI Grarup, Niels/0000-0001-5526-1070; Lahti, Jari/0000-0002-4310-5297; Deloukas, Panos/0000-0001-9251-070X; Wood, Lekki/0000-0001-7616-2119; Kovanen, Leena/0000-0002-3552-124X; Raikkonen, Katri/0000-0003-3124-3470; Linneberg, Allan/0000-0002-0994-0184; Partonen, Timo/0000-0003-1951-2455; Jorgensen, Torben/0000-0001-9453-2830; Eriksson, Johan/0000-0002-2516-2060 FU USDA [58-1950-0-014]; National Heart, Lung, and Blood Institute (NELBI) [BL105756]; NIH [R21 DK089378, RO1 HL094806]; Academy of Finland [136635, 139635]; Finnish Foundation for Cardiovascular Research; NHLBI [HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086]; NIMBI [HL080295, HL087652, HL105756, HL053916]; National Institute of Neurological Disorders and Stroke; National Institute on Aging [AG023629]; National Center for Advancing Translational Sciences; Clinical and Translational Science Institute (CTSI) [UL1TR000124]; National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center [DK063491]; NHLBI' s Framingham Heart Study [N01-HC-25195]; Affymetrix Inc. [NO2HL-6-4278]; Academy of Finland; Finnish Diabetes Research Society; Folkhalsan Research Foundation; [K08 HL112845-01] FX Supported by the USDA under agreement 58-1950-0-014. The Infrastructure for the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium is supported in part by National Heart, Lung, and Blood Institute (NELBI) grant BL105756. CES is supported by K08 HL112845-01. FAJLS was supported in part by NIH grants R21 DK089378 and RO1 HL094806. The Corogene Controls study was supported by the Academy of Finland (136635 and 139635) and the Finnish Foundation for Cardiovascular Research. CHS (Cardiovascular Health Study) research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086 and NIMBI grants HL080295, HL087652, HL105756, HL053916 with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided through AG023629 from the National Institute on Aging. The provision of genotyping data were supported in part by the National Center for Advancing Translational Sciences, Clinical and Translational Science Institute (CTSI) grant UL1TR000124, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center grant DK063491 to the Southern California Diabetes Endocrinology Research Center. The Framingham Offspring Study was conducted in part using data and resources from the Framingham Heart Study of the NIMBI of the NIH and Boston University School of Medicine. This work was partially supported by the NHLBI' s Framingham Heart Study (contract N01-HC-25195) and its contract with Affymetrix Inc. for genotyping services (contract NO2HL-6-4278). The Helsinki Birth Cohort Study has been supported by grants from the Academy of Finland, the Finnish Diabetes Research Society, the Folkhalsan Research Foundation, the Novo Nordisk Foundation, Finska Lalcaresallskapet, the Signe and Ane Gyllenberg Foundation, the University of Helsinki, the Ministry of Education, the Aliokas Foundation, and the Emil Aaltonen Foundation. The Invecchiare in Chianti (Aging in the Chianti Area) study baseline (1998-2000) was supported as a "targeted project" (ICS110.1/ RF97.71) by the Italian Ministry of Health and in part by the U.S. National Institute on Aging (contracts 263 MD 9164 and 263 MD 821336). The Inter99 was financially supported by research grants from the Danish Research Council, the Danish Centre for Health Technology Assessment, Novo Nordisk Inc., the Research Foundation of Copenhagen County, the Ministry of Internal Affairs and Health, the Danish Heart Foundation, the Danish Pharmaceutical Association, the Augustinus Foundation; the lb Henriksen Foundation, the Becket Foundation, and the Danish Diabetes Association. Genetic studies were supported by The Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention and Care (www.lucamp.org). The Novo Nordisk Foundation Center for Basic Metabolic Researeh is an independent Research Center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (www.metabol.ku.dk). The Multi-Ethnic Study of Atherosclerosis (MESA) is conducted and supported by contracts NO1HC-95159, N01-HC-95160, N01-HC-95161, NO1-HC-95162, N01-HC95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, NO1-HC-95169, and RR-024156 from the NHLBI. Funding for MESA SNP Health Association Resource (SHARe) genotyping was provided by NHLBI contract NO2-HL-6-4278.; For The Hellenic Study of Interactions between SNPs and Eating in Atherosclerosis Susceptibility study, PD is supported and funded by the National Institute for Health Research. The Cardiovascular.Risk in Young Finns Study has been financially supported by the Academy of Finland [grants 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117787 (Gendi), and 41071 (Slcidi)], the Social Insurance Institution of Finland, Kuopio, Tampere and Turku University Hospital Medical Funds (grant 9M048 for 9NO35 for TeLeht), the Juho Vainio Foundation, the Paavo Nurmi Foundation, the Finnish Foundation of Cardiovascular Research and Finnish Cultural Foundation, the Tampere Tuberculosis Foundation, and the Emil Aaltonen Foundation. NR 40 TC 21 Z9 21 U1 2 U2 36 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JAN PY 2015 VL 101 IS 1 BP 135 EP 143 DI 10.3945/ajcn.114.095026 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AX4ID UT WOS:000346895700016 PM 25527757 ER PT J AU Rautiainen, S Lee, IM Rist, PM Gaziano, JM Manson, JE Buring, JE Sesso, HD AF Rautiainen, Susanne Lee, I-Min Rist, Pamela M. Gaziano, J. Michael Manson, JoAnn E. Buring, Julie E. Sesso, Howard D. TI Multivitamin use and cardiovascular disease in a prospective study of women SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE multivitamin; cardiovascular disease; cohort; dietary supplements; epidemiology ID RANDOMIZED CONTROLLED-TRIAL; CORONARY-HEART-DISEASE; VITAMIN-E; MYOCARDIAL-INFARCTION; PRIMARY PREVENTION; PHYSICIANS HEALTH; BETA-CAROTENE; RISK; SUPPLEMENTS; MORTALITY AB Background: Although multivitamins are widely used, there are limited prospective studies investigating their association with both long- and short-term risk of cardiovascular disease (CVD). Objective: The objective was to investigate how multivitamin use is associated with the long- and short-term risk of CVD. Design: A prospective cohort study was conducted of 37,193 women from the Women's Health Study aged >= 45 y and free of CVD and cancer at baseline who were followed for an average of 16.2 y. At baseline, women self-reported a wide range of lifestyle, clinical, and dietary factors. Women were categorized into I) no current use and 2) current use of multivitamins. Duration and updated measures over the course of the follow-up to address short-term effects were also considered. Women were followed for major CVD events, including myocardial infarction (MI), stroke, and CVD death. Results: During the follow-up, 1493 incident cases of CVD [defined as myocardial infarction (MI), stroke, and CVD death] occurred. In multivariable analyses, multivitamin use compared with no use was not associated with major CVD events (HR: 1.01; 95% CI: 0.89, 1.15), MI (HR: 1.04; 95% CI: 0.84, 1.27), stroke (HR: 0.99; 95% CI: 0.83, 1.18), or CVD death (HR: 1.10; 95% CI: 0.84, 1.45). A nonsignificant inverse association was observed between baseline multivitamin use and major CVD events among women aged >= 70 y (P-interaction = 0.04) and those consuming <3 servings/d of fruit and vegetables (P-interaction = 0.01). When updating information on multivitamin use during the course of follow-up, no associations were observed for major CVD events (HR: 0.91; 95% CI: 0.82, 1.02), MI (HR: 0.89; 95% CI: 0.74, 1.06), stroke (HR: 0.91; 95% CI: 0.78, 1.06), and CVD death (HR: 0.91; 95% CI: 0.71, 1.16). Conclusions: In this study of middle-aged and elderly women, neither baseline nor time-varying multivitamin use was associated with the long-term risk of major CVD events, MI, stroke, cardiac revascularizations, or CVD death. Additional studies are needed to clarify the role of multivitamins on CVD. C1 [Rautiainen, Susanne] Karolinska Inst, Dept Inst Environm Med, Stockholm, Sweden. [Rautiainen, Susanne; Lee, I-Min; Rist, Pamela M.; Gaziano, J. Michael; Manson, JoAnn E.; Buring, Julie E.; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Gaziano, J. Michael; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. [Rist, Pamela M.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Lee, I-Min; Rist, Pamela M.; Manson, JoAnn E.; Buring, Julie E.; Sesso, Howard D.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Boston, MA USA. RP Rautiainen, S (reprint author), Brigham & Womens Hosp, Div Prevent Med, 900 Commonwealth Ave,3rd Floor, Boston, MA 02215 USA. EM susanne.rautiainen@ki.se FU NTH, Bethesda, MD [DK081141, CA047988, HL043851, HL080467, HL099355]; Swedish Council of Working Life and Social Research FX Supported by the NTH, Bethesda, MD (grants DK081141, CA047988, HL043851, HL080467, and HL099355) and the Swedish Council of Working Life and Social Research. NR 33 TC 5 Z9 5 U1 1 U2 12 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JAN PY 2015 VL 101 IS 1 BP 144 EP 152 DI 10.3945/ajcn.114.088310 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AX4ID UT WOS:000346895700017 PM 25527758 ER PT J AU Baron, JM Cheng, XXS Bazari, H Bhan, I Lofgren, C Jaromin, RT Lewandrowski, KB Dighe, AS AF Baron, Jason M. Cheng, Xingxing S. Bazari, Hasan Bhan, Ishir Lofgren, Christopher Jaromin, Rosemary T. Lewandrowski, Kent B. Dighe, Anand S. TI Enhanced Creatinine and Estimated Glomerular Filtration Rate Reporting to Facilitate Detection of Acute Kidney Injury SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Acute kidney injury (AKI); Creatinine; Estimated glomerular filtration rate (eGFR); Diagnostic error ID SERUM CREATININE; EQUATION AB Objectives: While acute kidney injury (AKI) can be diagnosed based on specified increases in a patient's plasma creatinine level, standard creatinine reporting methods typically only flag creatinine results as abnormal when outside the reference range and often fail to identify rising creatinine values indicative of AKI. Here, we evaluate the impact of this limitation in standard creatinine reporting and develop and implement an enhanced creatinine reporting algorithm. Methods: We evaluated 59,712 plasma creatinine results collected over approximately 3 months, using computational simulations and statistical analyses. Results: Our analyses demonstrated that 29% of creatinine results substantially increased over the patient's baseline and concerning for AKI remained within the normal reference range. These concerning results would not be flagged as abnormal using standard reporting. Likewise, we found that simple delta checks are also insensitive at AKI detection. To improve creatinine reporting, we developed and implemented an algorithm within our laboratory information system to alert clinicians to rising creatinine results, which we describe in this report. Conclusion: While both creatinine reference limits and simple delta checks are insensitive for AKI identification, a simple algorithm can be implemented within a common laboratory information system to enhance AKI identification. C1 [Baron, Jason M.; Lofgren, Christopher; Jaromin, Rosemary T.; Lewandrowski, Kent B.; Dighe, Anand S.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Baron, Jason M.; Cheng, Xingxing S.; Bazari, Hasan; Bhan, Ishir; Lewandrowski, Kent B.; Dighe, Anand S.] Harvard Univ, Sch Med, Boston, MA USA. [Cheng, Xingxing S.; Bazari, Hasan; Bhan, Ishir] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Bazari, Hasan; Bhan, Ishir] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. RP Dighe, AS (reprint author), Massachusetts Gen Hosp, Dept Pathol, Bigelow Bldg,Room 510A,55 Fruit St, Boston, MA 02114 USA. EM asdighe@partners.org NR 19 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 EI 1943-7722 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JAN PY 2015 VL 143 IS 1 BP 42 EP 49 DI 10.1309/AJCP05XBCQPHTLGQ PG 8 WC Pathology SC Pathology GA AX2FB UT WOS:000346757900008 PM 25511141 ER PT J AU Cohen, JM Nazarian, RM Ferry, JA Takvorian, RW Carter, JB AF Cohen, Jeffrey M. Nazarian, Rosalynn M. Ferry, Judith A. Takvorian, Ronald W. Carter, Joi B. TI Rare Presentation of Secondary Cutaneous Involvement by Splenic Marginal Zone Lymphoma: Report of a Case and Review of the Literature SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Review DE B-cell lymphoma; cutaneous lymphoma; splenic marginal zone lymphoma; chemotherapy ID B-CELL LYMPHOMA; CLASSIFICATION; RITUXIMAB; LEUKEMIA AB Cutaneous lymphomas encompass a broad spectrum of malignancies, including both primary and secondary cutaneous lymphomas. Determining the exact subtype of cutaneous lymphoma offers prognostic importance and directs therapeutic decisions. We describe the case of a 67-year-old woman with cutaneous involvement of splenic marginal zone lymphoma successfully treated with rituximab and bendamustine. We discuss the diagnostic work-up, including the histopathologic findings and treatment of this disease. C1 [Cohen, Jeffrey M.] Harvard Univ, Sch Med, Boston, MA USA. [Nazarian, Rosalynn M.; Ferry, Judith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Div Hematol Oncol, Boston, MA USA. [Takvorian, Ronald W.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Div Hematol Oncol, Boston, MA USA. [Carter, Joi B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. RP Carter, JB (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 2nd Floor,50 Staniford Sreet, Boston, MA 02114 USA. EM jcarter9@partners.org NR 18 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0193-1091 EI 1533-0311 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD JAN PY 2015 VL 37 IS 1 BP E1 EP E4 PG 4 WC Dermatology SC Dermatology GA AX6ZD UT WOS:000347065600001 PM 25238446 ER PT J AU Kelly, JF Wakeman, SE Saitz, R AF Kelly, John F. Wakeman, Sarah E. Saitz, Richard TI Stop Talking 'Dirty': Clinicians, Language, and Quality of Care for the Leading Cause of Preventable Death in the United States SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID STIGMA C1 [Kelly, John F.; Wakeman, Sarah E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kelly, John F.] Harvard Univ, Sch Med, Boston, MA USA. [Saitz, Richard] Boston Univ, Med Ctr, Boston, MA USA. RP Kelly, JF (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 6 TC 15 Z9 15 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD JAN PY 2015 VL 128 IS 1 BP 8 EP 9 DI 10.1016/j.amjmed.2014.07.043 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AX6KB UT WOS:000347030100017 PM 25193273 ER PT J AU Cheng, XXS Adusumalli, S Singh, H DePasse, JW Smith, RN Haupert, GT AF Cheng, Xingxing S. Adusumalli, Srinath Singh, Harshabad DePasse, Jacqueline W. Smith, R. Neal Haupert, Garner T. TI The Root of This Evil: Microangiopathic Hemolytic Anemia and Renal Failure SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID THROMBOTIC THROMBOCYTOPENIC PURPURA; UREMIC SYNDROME; MALIGNANT HYPERTENSION; TTP C1 [Haupert, Garner T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol, Boston, MA USA. [Cheng, Xingxing S.; Adusumalli, Srinath; Singh, Harshabad; DePasse, Jacqueline W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Med, Boston, MA USA. [Smith, R. Neal] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Haupert, GT (reprint author), Massachusetts Gen Hosp, Div Nephrol, 165 Cambridge St,Suite 302, Boston, MA 02114 USA. EM gthaupert@partners.org NR 8 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD JAN PY 2015 VL 128 IS 1 BP 21 EP 23 DI 10.1016/j.amjmed.2014.08.021 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AX6KB UT WOS:000347030100020 PM 25218936 ER PT J AU Avadhani, R Fowler, K Barbato, C Thomas, S Wong, W Paul, C Aksakal, M Hauser, TH Weinger, K Goldfine, AB AF Avadhani, Radhika Fowler, Kristen Barbato, Corinne Thomas, Sherine Wong, Winnie Paul, Camille Aksakal, Mehmet Hauser, Thomas H. Weinger, Katie Goldfine, Allison B. TI Glycemia and Cognitive Function in Metabolic Syndrome and Coronary Heart Disease SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Cardiovascular disease; Cognitive function; Glycemia; Hemoglobin A(1c) ID AMYLOID BETA-PROTEIN; DIABETES-MELLITUS; ALZHEIMERS-DISEASE; VASCULAR DEMENTIA; PERFORMANCE; ADULTS; IMPAIRMENT; RISK; AGE; HYPERGLYCEMIA AB OBJECTIVE: Higher hemoglobin A(1c) (HbA(1c)) is associated with lower cognitive function in type 2 diabetes. To determine whether associations persist at lower levels of dysglycemia in patients who have established cardiovascular disease, cognitive performance was assessed in the Targeting INflammation Using SAL-salate in CardioVascular Disease (TINSAL-CVD) trial. METHODS: The age-adjusted relationships between HbA(1c) and cognitive performance measured by the Mini-Mental State Examination, Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, Trail Making Test, and Categorical Verbal Fluency were assessed in 226 men with metabolic syndrome and established stable coronary artery disease. RESULTS: Of the participants, 61.5% had normoglycemia, 20.8% had impaired fasting glucose, and 17.7% had type 2 diabetes. HbA(1c) was associated with cognitive function tests of Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, Trail Making Test, and Categorical Verbal Fluency (all P < .02), but not the Mini-Mental State Examination. In an age-adjusted model, a 1% (11 mmol/mol) higher HbA(1c) value was associated with a 5.9 lower Digit Symbol Substitution Test score (95% confidence interval [CI], -9.58 to -2.21; P < .0001); a 2.44 lower Rey Auditory Verbal Learning Test score (95% CI, -4.00 to -0.87; P < .0001); a 15.6 higher Trail Making Test score (95% CI, 5.73 to 25.6; P < .0001); and a 3.71 lower Categorical Verbal Fluency score (95% CI, -6.41 to -1.01; P < .02). In a multivariate model adjusting for age, education, and cardiovascular covariates, HbA(1c) remained associated with cognitive function tests of Rey Auditory Verbal Learning Test (R-2 = 0.27, P < .0001), Trail Making Test (R-2 = 0.18, P < .0001), and Categorical Verbal Fluency (R-2 = 0.20, P < .0001), although association with the Digit Symbol Substitution Test was reduced. CONCLUSIONS: Higher HbA(1c) is associated with lower cognitive function performance scores across multiple domain tests in men with metabolic syndrome and coronary artery disease. Future studies may demonstrate whether glucose lowering within the normative range improves cognitive health. (c) 2015 Elsevier Inc. All rights reserved. C1 [Avadhani, Radhika; Fowler, Kristen; Barbato, Corinne; Thomas, Sherine; Wong, Winnie; Paul, Camille; Aksakal, Mehmet; Weinger, Katie; Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Hauser, Thomas H.; Goldfine, Allison B.] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Hauser, Thomas H.; Weinger, Katie; Goldfine, Allison B.] Harvard Univ, Sch Med, Boston, MA USA. RP Goldfine, AB (reprint author), Joslin Diabet Ctr, One Joslin Pl, Boston, MA 02215 USA. EM allison.goldfine@joslin.harvard.edu OI Fowler, Kristen/0000-0003-0196-5747 FU [P50HL083813]; [P30DK036836] FX P50HL083813 and P30DK036836. NR 40 TC 2 Z9 2 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD JAN PY 2015 VL 128 IS 1 BP 46 EP 55 DI 10.1016/j.amjmed.2014.08.025 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AX6KB UT WOS:000347030100025 PM 25220612 ER PT J AU Temtanakitpaisan, Y Kilari, S Damrongwatanasuk, R AF Temtanakitpaisan, Yutthapong Kilari, Sneha Damrongwatanasuk, Rongras TI Use of Digoxin in Chronic Systolic Heart Failure in Current Era SO AMERICAN JOURNAL OF MEDICINE LA English DT Letter C1 [Temtanakitpaisan, Yutthapong] VA Boston Healthcare Syst, Boston Med Ctr, Dept Med, Div Cardiol, W Roxbury, MA 02132 USA. [Kilari, Sneha] MetroWest Med Ctr, Dept Med, Framingham, MA USA. [Damrongwatanasuk, Rongras] Johns Hopkins Univ, Sinai Hosp Baltimore, Dept Med, Baltimore, MD USA. RP Temtanakitpaisan, Y (reprint author), VA Boston Healthcare Syst, Boston Med Ctr, Dept Med, Div Cardiol, W Roxbury, MA 02132 USA. NR 2 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD JAN PY 2015 VL 128 IS 1 BP E13 EP E13 DI 10.1016/j.amjmed.2014.03.030 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AX6KB UT WOS:000347030100009 PM 25553632 ER PT J AU Yu, DM Mathews, CA Scharf, JM Neale, BM Davis, LK Gamazon, ER Derks, EM Evans, P Edlund, CK Crane, J Osiecki, L Gallagher, P Gerber, G Haddad, S Illmann, C McGrath, LM Mayerfeld, C Arepalli, S Barlassina, C Barr, CL Bellodi, L Benarroch, F Berrio, GB Bienvenu, OJ Black, DW Bloch, MH Brentani, H Bruun, RD Budman, CL Camarena, B Campbell, DD Cappi, C Silgado, JCC Cavallini, MC Chavira, DA Chouinard, S Cook, EH Cookson, MR Coric, V Cullen, B Cusi, D Delorme, R Denys, D Dion, Y Eapen, V Egberts, K Falkai, P Fernandez, T Fournier, E Garrido, H Geller, D Gilbert, DL Girard, SL Grabe, HJ Grados, MA Greenberg, BD Gross-Tsur, V Grunblatt, E Hardy, J Heiman, GA Hemmings, SMJ Herrera, LD Hezel, DM Hoekstra, PJ Jankovic, J Kennedy, JL King, RA Konkashbaev, AI Kremeyer, B Kurlan, R Lanzagorta, N Leboyer, M Leckman, JF Lennertz, L Liu, CY Lochner, C Lowe, TL Lupoli, S Macciardi, F Maier, W Manunta, P Marconi, M McCracken, JT Restrepo, SCM Moessner, R Moorjani, P Morgan, J Muller, H Murphy, DL Naarden, AL Nurmi, E Ochoa, WC Ophoff, RA Pakstis, AJ Pato, MT Pato, CN Piacentini, J Pittenger, C Pollak, Y Rauch, SL Renner, T Reus, VI Richter, MA Riddle, MA Robertson, MM Romero, R Rosario, MC Rosenberg, D Ruhrmann, S Sabatti, C Salvi, E Sampaio, AS Samuels, J Sandor, P Service, SK Sheppard, B Singer, HS Smit, JH Stein, DJ Strengman, E Tischfield, JA Turiel, M Duarte, AVV Vallada, H Veenstra-VanderWeele, J Walitza, S Wang, Y Weale, M Weiss, R Wendland, JR Westenberg, HGM Shugart, YY Hounie, AG Miguel, EC Nicolini, H Wagner, M Ruiz-Linares, A Cath, DC McMahon, W Posthuma, D Oostra, BA Nestadt, G Routeau, GA Purcell, S Jenike, MA Heutink, P Hanna, GL Conti, DV Arnold, PD Freimer, NB Stewart, E Knowles, JA Cox, NJ Pauls, DL AF Yu, Dongmei Mathews, Carol A. Scharf, Jeremiah M. Neale, Benjamin M. Davis, Lea K. Gamazon, Eric R. Derks, Eske M. Evans, Patrick Edlund, Christopher K. Crane, Jacquelyn Osiecki, Lisa Gallagher, Patience Gerber, Gloria Haddad, Stephen Illmann, Cornelia McGrath, Lauren M. Mayerfeld, Catherine Arepalli, Sampath Barlassina, Cristina Barr, Cathy L. Bellodi, Laura Benarroch, Fortu Berrio, Gabriel Bedoya Bienvenu, O. Joseph Black, Donald W. Bloch, Michael H. Brentani, Helena Bruun, Ruth D. Budman, Cathy L. Camarena, Beatriz Campbell, Desmond D. Cappi, Carolina Silgado, Julio C. Cardona Cavallini, Maria C. Chavira, Denise A. Chouinard, Sylvain Cook, Edwin H. Cookson, M. R. Coric, Vladimir Cullen, Bernadette Cusi, Daniete Delorme, Richard Denys, Damiaan Dion, Yves Eapen, Valsama Egberts, Karin Falkai, Peter Fernandez, Thomas Fournier, Eduardo Garrido, Helena Geller, Daniel Gilbert, Donald L. Girard, Simon L. Grabe, Hans J. Grados, Marco A. Greenberg, Benjamin D. Gross-Tsur, Varda Gruenblatt, Edna Hardy, John Heiman, Gary A. Hemmings, Sian M. J. Herrera, Luis D. Hezel, Dianne M. Hoekstra, Pieter J. Jankovic, Joseph Kennedy, James L. King, Robert A. Konkashbaev, Anuar I. Kremeyer, Barbara Kurlan, Roger Lanzagorta, Nuria Leboyer, Marion Leckman, James F. Lennertz, Leonhard Liu, Chunyu Lochner, Christine Lowe, Thomas L. Lupoli, Sara Macciardi, Fabio Maier, Wolfgang Manunta, Paolo Marconi, Maurizio McCracken, James T. Restrepo, Sandra C. Mesa Moessner, Rainald Moorjani, Priya Morgan, Jubel Muller, Heike Murphy, Dennis L. Naarden, Allan L. Nurmi, Erika Ochoa, William Cornejo Ophoff, Roel A. Pakstis, Andrew J. Pato, Michele T. Pato, Carlo N. Piacentini, John Pittenger, Christopher Pollak, Yehuda Rauch, Scott L. Renner, Tobias Reus, Victor I. Richter, Margaret A. Riddle, Mark A. Robertson, Mary M. Romero, Roxana Rosario, Maria C. Rosenberg, David Ruhrmann, Stephan Sabatti, Chiara Salvi, Erika Sampaio, Aline S. Samuels, Jack Sandor, Paul Service, Susan K. Sheppard, Brooke Singer, Harvey S. Smit, Jan H. Stein, Dan J. Strengman, Eric Tischfield, Jay A. Turiel, Maurizio Duarte, Ana V. Valencia Vallada, Homero Veenstra-VanderWeele, Jeremy Walitza, Susanne Wang, Ying Weale, Mike Weiss, Robert Wendland, Jens R. Westenberg, Herman G. M. Shugart, Yin Yao Hounie, Ana G. Miguel, Euripedes C. Nicolini, Humberto Wagner, Michael Ruiz-Linares, Andres Cath, Danielle C. McMahon, William Posthuma, Danielle Oostra, Ben A. Nestadt, Gerald Routeau, Guy A. Purcell, Shaun Jenike, Michael A. Heutink, Peter Hanna, Gregory L. Conti, David V. Arnold, Paul D. Freimer, Nelson B. Stewart, Evelyn Knowles, James A. Cox, Nancy J. Pauls, David L. TI Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; ASSOCIATION SCANS; GENERALIST GENES; VARIANTS; TICS AB Objective: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD. Method: The authors conducted a GWAS in 2,723 cases (1,310 with OCD, 834 with Tourette's syndrome, 579 with OCD plus Tourette's syndrome/chronic tics), 5,667 ancestry-matched controls, and 290 OCD parent-child trios. GWAS summary statistics were examined for enrichment of functional variants associated with gene expression levels in brain regions. Polygenic score analyses were conducted to investigate the genetic architecture within and across the two disorders. Results: Although no individual single-nucleotide polymorphisms (SNPs) achieved genome-wide significance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels (expression quantitative loci, or eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders Polygenic score analyses identified a significant polygenic component for OCD (p=2x10(-4)), predicting 3.2% of the phenotypic variance in an independent data set. In contrast, Tourette's syndrome had a smaller, nonsignificant polygenic component, predicting only 0.6% of the phenotypic variance (p=0.06). No significant polygenic signal was detected across the two disorders, although the sample is likely underpowered to detect a modest shared signal. Furthermore, the OCD polygenic signal was significantly attenuated when cases with both OCD and co-occurring Tourette's syndrome/chronic tics were included in the analysis (p=0.01). Conclusions: Previous work has shown that Tourette's syndrome and OCD have some degree of shared genetic variation. However, the data from this study suggest that there are also distinct components to the genetic architectures of these two disorders. Furthermore, OCD with co-occurring burette's syndrome/chronic tics may have different underlying genetic susceptibility compared with OCD alone. C1 [Yu, Dongmei] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Dept Psychiat,Psychiat & Neur, Boston, MA 02138 USA. Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Cognit & Behav Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. Univ Chicago, Dept Med, Med Genet Sect, Chicago, IL 60637 USA. Univ Amsterdam, Acad Med Ctr, Dept Psychiat, NL-1105 AZ Amsterdam, Netherlands. Univ So Calif, Keck Sch Med, Dept Prevent Med, Div Biostat, Los Angeles, CA 90033 USA. NIA, Neurogenet Lab, Bethesda, MD 20892 USA. Filarete Fdn, Genom & Bioinformat Unit, Milan, Italy. Univ Milan, Dept Hlth Sci, Grad Sch Nephrol, Milan, Italy. Univ Hlth Network, Toronto Western Res Inst, Toronto, ON, Canada. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Univ Vita Salute San Raffaele, Milan, Italy. Hadassah Hebrew Univ, Med Ctr, Herman Dana Div Child & Adolescent Psychiat, Jerusalem, Israel. Univ Pontificia Bolivariana, Univ Antioquia, Medellin, Colombia. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Univ Iowa, Dept Psychiat, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA. Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. North Shore Long Isl Jewish Med Ctr, Manhasset, NY USA. North Shore Long Isl Jewish Hlth Syst, Manhasset, NY USA. NYU, Med Ctr, New York, NY 10016 USA. Hofstra Univ, Sch Med, Hempstead, NY 11550 USA. Inst Nacl Psiquiatria Ramon de la Fuente Muniz, Mexico City, DF, Mexico. UCL, London, England. Univ Hong Kong, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China. Univ Milan, Osped San Raffaele, I-20127 Milan, Italy. Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. Univ Illinois, Dept Psychiat, Inst Juvenile Res, Chicago, IL 60612 USA. Inst Pasteur, Paris, France. French Natl Sci Fdn, Fdn FondaMental, Creteil, France. Hop Robert Debre, AP HP, Dept Child & Adolescent Psychiat, F-75019 Paris, France. Royal Netherlands Acad Arts & Sci, Netherlands Inst Neurosci, Amsterdam, Netherlands. Univ Montreal, Dept Psychiat, Montreal, PQ H3C 3J7, Canada. Univ New S Wales, Sydney, NSW 2052, Australia. South West Sydney Local Hlth Dist AUCS, Acad Unit Child Psychiat, Sydney, NSW, Australia. Univ Tubingen, Dept Child & Adolescent Psychiat & Psychotherapy, Tubingen, Germany. Univ Wurzburg, Dept Child & Adolescent Psychiat Psychosomat & Ps, D-97070 Wurzburg, Germany. Univ Munich, Dept Psychiat & Psychotherapy, Munich, Germany. Hosp Nacl Ninos Dr Carlos Saenz Herrera, San Jose, Costa Rica. Clin Herrera Amighetti, San Jose, Costa Rica. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,OCD Program, Boston, MA USA. Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. Univ Cincinnati, Cincinnati, OH USA. Univ Med Greffswatd, Hellos Hosp Stralsund, Dept Psychiat & Psychotherapy, Greifswald, Germany. Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA. Shaare Zedek Med Ctr, Neuropediat Unit, Jerusalem, Israel. Univ Zurich, Univ Clin Child Psychiat, Zurich, Switzerland. Univ Zurich, Univ Clin Adolescent Psychiat, Zurich, Switzerland. Rutgers State Univ, Dept Genet, Human Genet Inst New Jersey, Piscataway, NJ USA. Univ Stellenbosch, Dept Psychiat, ZA-7600 Stellenbosch, South Africa. Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands. Baylor Coll Med, Dept Neurol, Parkinsons Dis Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurol, Movement Disorders Clin, Houston, TX 77030 USA. Ctr Addict & Mental Hlth, Neurogenet Sect, Toronto, ON, Canada. Univ Toronto, Dept Psychiat, Toronto, ON, Canada. Overlook Hosp, Atlantic Neurosci Inst, Summit, NJ USA. Carracci Med Grp, Mexico City, DF, Mexico. Inst Mondor Rech Biomed, Creteil, France. Univ Bonn, Dept Psychiat & Psychotherapy, Bonn, Germany. Univ Illinois, Dept Psychiat, Inst Human Genet, Chicago, IL 60612 USA. Univ Stellenbosch, Dept Psychiat, MRC Unit Anxiety & Stress Disorders, ZA-7600 Stellenbosch, South Africa. Univ Cape Town, ZA-7700 Rondebosch, South Africa. Univ Calif Irvine, Sch Med, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. Univ Vita Salute San Raffaele, Milan, Italy. IRCCS San Raffaele Sci Inst, Milan, Italy. Fdn IRCCS CaGranda Osped Maggiore Policlin, Ctr Transfus Med & Immunohematol, Milan, Italy. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. Columbia Univ, Dept Biol Sci, New York, NY 10027 USA. Univ Utah, Salt Lake City, UT USA. NIMH Intramural Res Program, Clin Sci Lab, Bethesda, MD USA. Med City Dallas Hosp, Dept Clin Res, Dallas, TX USA. Univ Med Ctr, Rudolf Magnus Inst Neurosci, Dept Psychiat, Utrecht, Netherlands. Univ Calif Los Angeles, Ctr Neurobehav Genet, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. Partners Psychiat, Boston, MA USA. McLean Hosp, Boston, MA USA. Sunnybrook Hlth Sci Ctr, Frederick W Thompson Anxiety Disorders Ctr, Toronto, ON M4N 3M5, Canada. St Georges Hosp & Med Sch, London, England. Univ Fed Sao Paulo, Dept Psychiat, Child & Adolescent Psychiat Unit, Sao Paulo, Brazil. Wayne State Univ, Dept Psychiat & Behav Neurosci, Detroit, MI 48207 USA. Detroit Med Ctr, Detroit, MI USA. Univ Cologne, Dept Psychiat & Psychotherapy, D-50931 Cologne, Germany. Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA. Univ Fed Bahia, Univ Hlth Care Serv SMURB, Salvador, BA, Brazil. Univ Toronto, Dept Psychiat, Toronto, ON, Canada. Univ Hlth Network, Toronto Western Res Inst, Toronto, ON, Canada. Youthdate Treatment Ctr, Toronto, ON, Canada. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands. Univ Cape Town, ZA-7925 Cape Town, South Africa. Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. Univ Milan, Dept Hlth Technol, Milan, Italy. Vanderbilt Univ, Dept Psychiat, Kennedy Ctr Res Human Dev, Nashville, TN 37235 USA. Vanderbilt Univ, Dept Pediat, Kennedy Ctr Res Human Dev, Nashville, TN USA. Vanderbilt Univ, Dept Pharmacol, Kennedy Ctr Res Human Dev, Nashville, TN USA. Vanderbilt Univ, Inst Brain, Nashville, TN USA. Univ Wurzburg, Dept Child & Adolescent Psychiat, D-97070 Wurzburg, Germany. Weill Cornell Med Ctr, Dept Psychiat, Div Child & Adolescent Psychiat, New York, NY USA. Kings Coll London, Dept Med & Mol Genet, London WC2R 2LS, England. Royal Netherlands Acad Arts & Sci, Acad Med Ctr, Dept Psychiat, Amsterdam, Netherlands. Royal Netherlands Acad Arts & Sci, Netherlands Inst Neurosci, Amsterdam, Netherlands. NIMH Intramural Res Program, Unit Stat Genom, Bethesda, MD USA. Carracci Med Grp, Natl Inst Genom Med SAP, Mexico City, DF, Mexico. Univ Utrecht, Dept Clin & Hlth Psychol, Utrecht, Netherlands. Univ Utah, Dept Psychiat, Salt Lake City, UT USA. Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Sect Med Genom, Amsterdam, Netherlands. Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Funct Genom, Amsterdam, Netherlands. Erasmus Univ, Med Ctr, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands. Erasmus Univ, Med Ctr, Dept Clin Genet, Rotterdam, Netherlands. Mt Sinai Med Ctr, New York, NY 10029 USA. German Ctr Neurodegenerat Dis, Tubingen, Germany. Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1X8, Canada. Univ British Columbia, British Columbia Mental Hlth & Addict Res Inst, Vancouver, BC V5Z 1M9, Canada. RP Yu, DM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Dept Psychiat,Psychiat & Neur, Boston, MA 02138 USA. EM dyu@pngu.mgh.harvard.edu; dpauls@pngu.mgh.harvard.edu; dpauls@pngu.mgh.harvard.edu RI Derks, Eske/A-1652-2017; Vallada, Homero/D-1333-2014; Hardy, John/C-2451-2009; Stein, Dan/A-1752-2008; Salvi, Erika/C-1033-2015; Weale, Michael/F-2587-2010; reus, victor/I-7923-2015; Renner, Tobias/I-2120-2013; Veenstra-VanderWeele, Jeremy/K-1935-2015; Grunblatt, Edna/A-6762-2016; Macciardi, Fabio/N-3768-2014; Wagner, Michael/E-2325-2011; Brentani, Helena/G-6839-2011 OI Derks, Eske/0000-0002-6292-6883; Campbell, Desmond/0000-0003-1085-714X; Barr, Cathy/0000-0003-0361-0106; Nicolini, Humberto/0000-0003-2494-0067; Hanna, Gregory/0000-0002-0742-6990; Walitza, Susanne/0000-0002-8161-8683; Hemmings, Sian/0000-0001-8461-1017; Lanzagorta, Nuria/0000-0001-6769-6813; Vallada, Homero/0000-0001-5123-8295; Stein, Dan/0000-0001-7218-7810; Salvi, Erika/0000-0002-2724-2291; Weale, Michael/0000-0003-4593-1186; reus, victor/0000-0002-8193-5697; Veenstra-VanderWeele, Jeremy/0000-0002-6349-1076; Grunblatt, Edna/0000-0001-8505-7265; Macciardi, Fabio/0000-0003-0537-4266; Wagner, Michael/0000-0003-2589-6440; Brentani, Helena/0000-0001-5192-4682 FU David Judah Fund; NIH [NS40024, NS16648, MH079489, MH073250, NS037484, MH085057, MH079494, MH71507]; Tourette Syndrome Association International Consortium for Genetics; Tourette Syndrome Association; OCD Collaborative Genetics Association Study; American Academy of Child and Adolescent Psychiatry Early Investigator Research Grant; Anxiety Disorders Association of America Junior Investigator Research Grant; University of British Columbia; Michael Smith Foundation Clinical Research Scholar Award; American Recovery and Reinvestment Act awards [NS40024-0751, NS16648-29S1]; UCLA Informatics Center for Neurogenetics and Neurogenomics [R01 MH090937, P50MH094267, P30NS062691]; New Jersey Center for Tourette Syndrome and Associated Disorders; NIMH [R01MH092293]; Medical Research Council of South Africa; NIH Genes, Environment, and Health Initiative [GEI] [U01 HG004422]; Gene Environment Association Studies (GENEVA) under GEL Assistance; GENEVA Coordinating Center [U01 HG004446]; Collaborative Study on the Genetics of Alcoholism [U10 AA008401]; Collaborative Genetic Study of Nicotine Dependence [P01 CA089392]; Family Study of Cocaine Dependence [R01 DA013423]; NIH GEI [U01HG004438]; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; NIH contract "High Throughput Genotyping for Studying the Genetic Contributions to Human Disease" [HHSN268200782096C]; European Union, HYPERGENES [FP7-HEALTH-2007-A-201550]; InterOmics [PB05]; Tourette Syndrome Association (TSA); Astra-Zeneca; Psyadon; AstraZeneca; Otsuka; U.S. national Tourette Syndrome Association; Medtronic; NIMH; Simons Foundation; Allison Foundation; German Research Foundation; Federal Ministry of Education, and Research Germany; NIH; Grifots; Klingenstein Third Generation Foundation; Pfizer Pharmaceuticals via the Duke University Clinical Research Institute; burette Syndrome Association; Pettit Family Foundation; Medtronic and Cyberonics; U.K. Tourette Syndrome Association; U.S. Tourette Syndrome Association; COST/ESSTS (the European Society for the Study of Tourette Syndrome); Roche; AMBRF; Biocodex; Cipla; Lundbeck; National Responsible Gambling Foundation; Novartis; Servier; SynapDx; Seaside Therapeutics; Forest; Pherin Pharmaceuticals; Transcept Pharmaceuticals; DNA Genotek; BioMarin FX Supported by a grant from the David Judah Fund; NIH grant NS40024 to Drs. Pauts and Scharf, the Tourette Syndrome Association International Consortium for Genetics; NIH grants NS16648, MH079489, and. MH073250 to Dr. Pauls; NIH grant NS037484 to Dr. Freimer; a grant from the Tourette Syndrome Association and NIH grant MH085057 to Dr. Scharf, grant MH079494 to Dr. Knowles, MH71507 to Dr. McCracken; the OCD Collaborative Genetics Association Study, which supported the imputation; an American Academy of Child and Adolescent Psychiatry Early Investigator Research Grant, an Anxiety Disorders Association of America Junior Investigator Research Grant, the University of British Columbia, and a Michael Smith Foundation Clinical Research Scholar Award to Dr. Stewart; American Recovery and Reinvestment Act awards NS40024-0751 to Drs: Pauls and Scharf and NS16648-29S1 to Dr. Pauls Additional support for analysis was provided by grants R01 MH090937 and P50MH094267 to Dr. Cox and by grant P30NS062691 from the UCLA Informatics Center for Neurogenetics and Neurogenomics to Dr. Freimer. Dr. Heiman and Dr. Tischfield received support from the New Jersey Center for Tourette Syndrome and Associated Disorders and NIMH grant R01MH092293. Dr. Stein and Dr. Lochner are supported by the Medical Research Council of South Africa. Funding support for the Study of Addiction: Genetics and Environment (SAGE),was provided through the NIH Genes, Environment, and Health Initiative [GEI] (grant U01 HG004422) SAGE is one of the genome-wide association studies funded as part of the Gene Environment Association Studies (GENEVA) under GEL Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (grant U01 HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information Support for collection of data sets and samples was provided by the Collaborative Study on the Genetics of Alcoholism (grant U10 AA008401), the Collaborative Genetic Study of Nicotine Dependence (grant P01 CA089392), and the Family Study of Cocaine Dependence (grant R01 DA013423). Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the NIH GEI (grant U01HG004438), the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, and the NIH contract "High Throughput Genotyping for Studying the Genetic Contributions to Human Disease" (grant HHSN268200782096C) The data sets used for the analyses in this study were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/projects/gap/cgibin/study.cgi?study_id-phs00 0092.v1.p1 through dbGaP accession number phs000092.v1.p. The European Union (grant FP7-HEALTH-2007-A-201550), HYPERGENES, and InterOmics (PB05 MIUR-CNR Italian Flagship Project) provided financial support for the genotyping of Italian controls.; Dr. Scharf has received research support and travel support from the Tourette Syndrome Association (TSA); he also serves on the TSA Scientific Advisory Board. Dr. Black receives research support from Astra-Zeneca and royalties from American Psychiatric Publishing, Oxford University Press, and UpToDate. Dr. Budman has received research grant support from Psyadon, AstraZeneca, and Otsuka, and has served as a speaker for the National Tourette Syndrome Association-CDC Partnership. Dr. Cook served as a consultant and was a site principal investigator for a Seaside Therapeutics clinical trial in autism spectrum disorder. Dr. Coric is an employee of Bristol-Myers Squibb and owns stock in the company; his regarding this study stems from his work at Yale University, and no financial or other support for this study was obtained from Bristol-Myers Squibb. Dr. Denys received a grant from the U.S. national Tourette Syndrome Association; he is a member of the advisory board of Lundbeck and he receives consultant fees from Medtronic for educational purposes. Dr. Fernandez has received research funding from NIMH, the Simons Foundation, the Allison Foundation, and Shire. Dr. Gilbert has served as a site investigator for clinical trials in Tourette's syndrome for Otsuka, Psyadon, and AstraZeneca. Dr. Grabe has received research support from the German Research Foundation, the Federal Ministry of Education, and Research Germany and has received speaking honoraria from Servier and Eli Lilly. Dr. Hardy has served as a consultant for Eisai and has been on speakers bureaus for Takeda, Eli Lilly, and Roche. Dr. Kennedy has received honoraria from Roche, Novartis, and Eli Lilly; he serves as an non-paid member of AssureRx Health Scientific Advisory Board. Dr. Leckman has received research support from NIH, the Tourette Syndrome Association, Grifots, and Klingenstein Third Generation Foundation, and royalties from John Wiley & Sons, McGraw-Hill, Oxford University Press. Dr. Piacentini has received research support from Pfizer Pharmaceuticals via the Duke University Clinical Research Institute and from the burette Syndrome Association; speaking/travel support from the Tourette Syndrome Association and the International OCD Foundation; financial support from the Pettit Family Foundation; and royalties from Oxford University Press and Guilford Press Dr Pittenger has served as a consultant for Roche Dr. Rauch has participated in research funded by Medtronic and Cyberonics. Dr. Richter has received speaking honoraria from Lundbeck. Dr. Robertson has received support from the U.K. Tourette Syndrome Association, the U.S. Tourette Syndrome Association, and COST/ESSTS (the European Society for the Study of Tourette Syndrome); speaking honoraria from Janssen-Cilag and Flynn Pharma; and royalties from Wiley-Blackwell, Oxford University Press, David Fulton/Granada/Taylor Francis, and Jessica Kingsley Publishers. Dr. Rosario has served on speakers bureaus for Novartis and Shire. Dr. Rosenberg has served as a consultant for Shire Dr Ruhrmann has received speaking honoraria from Roche, Otsuka, Lundbeck, and Johnson & Johnson and travel funds from Roche and Servier. Dr. Sandor has received research support from Otsuka and speaking honoraria from Purdue Pharma, Dr. Stein has received research grants from and/or served as a consultant to AMBRF, Biocodex, Cipla, Lundbeck, National Responsible Gambling Foundation, Novartis, Servier, and Sun. Dr. Veenstra-VanderWeele has served as a consultant for Novartis.; Roche, and SynapDx and received research funding from Novartis, Roche, SynapDx, Seaside Therapeutics, Forest, and Sunovion. Dr. Walitza has received speaking honoraria from Janssen Cilag, AstraZeneca, and Eli Lilly. Dr. Wend land is a former employee of Hoffmann-La Roche (2010-2012) and is now an employee of Pfizer (2012-present). Dr. Nicolini has received research funds from Pherin Pharmaceuticals, Transcept Pharmaceuticals, and En Vivo and speaking honoraria from MSD and Landsteiner Mexico. Dr. Arnold has received an unrestricted research grant from DNA Genotek. Dr. Knowles received a speaking honorarium from Illumina, Inc. Dr. McCracken has received research support from and/or served as a consultant to Roche, Seaside Therapeutics, and BioMarin. The other authors report no financial relationships with commercial interests. NR 35 TC 20 Z9 20 U1 10 U2 50 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 2015 VL 172 IS 1 BP 82 EP 93 DI 10.1176/appi.ajp.2014.13101306 PG 12 WC Psychiatry SC Psychiatry GA AX8FQ UT WOS:000347146000013 PM 25158072 ER PT J AU Oates, JC AF Oates, Jim C. TI Endothelial Dysfunction in Injury and Inflammation SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Editorial Material C1 [Oates, Jim C.] Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [Oates, Jim C.] Ralph H Johnson VA Med Ctr, Med Serv, Rheumatol Sect, Charleston, SC USA. [Oates, Jim C.] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC USA. RP Oates, JC (reprint author), Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, 96 Jonathan Lucas St,Suite 816,MSC 637, Charleston, SC 29425 USA. EM oatesjc@musc.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0002-9629 EI 1538-2990 J9 AM J MED SCI JI Am. J. Med. Sci. PD JAN PY 2015 VL 349 IS 1 BP 2 EP 2 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AX7CS UT WOS:000347075200003 PM 25535885 ER PT J AU Manian, FA Manian, CJ AF Manian, Farrin A. Manian, Cyrus J. TI Sleep Quality in Adult Hospitalized Patients With Infection: An Observational Study SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Sleep; Infection; Hospital; Pain; Staff disruption; Anxiety ID MEDICAL PATIENTS; PAIN-CONTROL; DEPRIVATION; ANXIETY; CARE; DOCUMENTATION; SATISFACTION; PERCEPTION; SYMPTOMS; WOMEN AB Background: Sleep deprivation may adversely affect host defenses against infection while infection may impact sleep. We studied sleep quality in hospitalized patients with infection-related diagnoses. Methods: This was an observational study in a 900-bed tertiary care community teaching hospital involving consecutive patients seen by an infectious disease consultant from June 26, 2008 to December 31, 2011. During routine part of their care, patients were enquired about their sleep quality, categorized into either "sound" or "unsound" sleep and the reason (s) for experiencing unsound sleep. Results: Of 1,238 unique patients (mean age, 59 years), 592 (47.8%) reported unsound sleep. Patients of 50 years or younger were more likely to report unsound sleep compared with those in the age groups of 50 to 79 years (57.1% versus 45.7%) and 80 years or older (57.1% versus 36.5%) (OR: 1.58 [95% CI: 1.23-2.0] and OR: 2.32 [95% CI: 1.59-3.38], respectively). Skin and soft tissue infections, central nervous system infections, osteomyelitis/diskitis and the head and neck infections were associated with >= 50% rates of unsound sleep. Staff disruptions, pain and anxiety were the most commonly cited reasons for unsound sleep (28.9%, 26.4% and 9.6%, respectively). Patients receiving sedating and/or hypnotic medications were no more likely to report sound sleep, compared with those not receiving such medications (50.7% versus 58.7%, respectively, OR: 0.71 [95% CI: 0.5-1.00]). Conclusions: Self-reported unsound sleep is common among hospitalized patients with an infection-related diagnosis, is associated with less advanced age and is often attributed to staff disruptions, pain and/or anxiety. Interventions at improving sleep quality in this patient population seem warranted. C1 [Manian, Farrin A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Manian, Cyrus J.] Univ Missouri, Dept Psychol, Kansas City, MO 64110 USA. RP Manian, FA (reprint author), Massachusetts Gen Hosp, Dept Med, 50 Staniford St,Suite 503B, Boston, MA 02114 USA. EM fmanian@mgh.harvard.edu NR 35 TC 3 Z9 3 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0002-9629 EI 1538-2990 J9 AM J MED SCI JI Am. J. Med. Sci. PD JAN PY 2015 VL 349 IS 1 BP 56 EP 60 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA AX7CS UT WOS:000347075200013 PM 25319438 ER PT J AU Almassi, GH Wagner, TH Carr, B Hattler, B Collins, JF Quin, JA Ebrahimi, R Grover, FL Bishawi, M Shroyer, ALW AF Almassi, G. Hossein Wagner, Todd H. Carr, Brendan Hattler, Brack Collins, Joseph F. Quin, Jacquelyn A. Ebrahimi, Ramin Grover, Frederick L. Bishawi, Muath Shroyer, A. Laurie W. CA VA 517 Randomized On Off Bypass RO TI Postoperative Atrial Fibrillation Impacts on Costs and One-Year Clinical Outcomes: The Veterans Affairs Randomized On/Off Bypass Trial SO ANNALS OF THORACIC SURGERY LA English DT Article ID QUALITY-OF-LIFE; CARDIAC-SURGERY; HOSPITAL STAY; HEALTH; MORTALITY; PREDICTORS; ABLATION; PUMP AB Background. New-onset postoperative atrial fibrillation (POAF) after coronary artery bypass graft surgery (CABG) is associated with worse in-hospital morbidity and mortality, extended hospital stays, and higher costs. Beyond the initial hospital discharge, the cost and outcomes of POAF have not been well studied. Methods. For CABG patients with and without new-onset POAF, a retrospective propensity-matched, multi-variable regression analysis was performed to compare 1-year outcomes (including health-related quality of life [HRQoL] scores and mortality rates) and costs (standardized to 2010 dollars). Regression models controlled for site and patient factors, with propensity matching used to adjust for differences in POAF versus no-POAF patients' risk profiles. Results. Using the existing CABG trial database, 2,096 patient records were analyzed, including POAF patients (n = 549) versus no-POAF patients (n = 1,547). For the index CABG hospitalization, POAF patients had longer postoperative length of stay (+/-3.9 days) and higher discharge costs (+$13,993) than no-POAF patients. At 1 year, POAF patients had more than twice the adjusted odds of dying (p < 0.01), with higher 1-year total cumulative costs. This 1-year cost difference (+$15,593) was largely attributable to hospital-based costs during the index surgery hospitalization. There was no difference in 1-year HRQoL scores (or HRQoL score changes) between POAF patients and no-POAF patients. Conclusions. Compared with no-POAF patients, POAF patients had higher discharge and 1-year costs along with higher 1-year mortality rates, but no differences were observed in 1-year HRQoL scores. Additional research appears warranted to improve the longer-term survival rates for POAF CABG patients, targeting future POAF-specific postdischarge interventions. (C) 2015 by The Society of Thoracic Surgeons C1 Zablocki Vet Affairs Med Ctr, Milwaukee, WI USA. [Almassi, G. Hossein] Med Coll Wisconsin, Milwaukee, WI 53226 USA. Vet Affairs Palo Alto Hlth Econ Resource Ctr, Menlo Pk, CA USA. Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA. Northport Vet Affair Med Ctr, Northport, NY USA. Eastern Colorado Hlth Care Syst, Dept Vet Affairs, Denver, CO USA. Univ Colorado, Sch Med, Anschutz Med Campus, Aurora, CO USA. Vet Affairs Med Ctr, Cooperat Studies Program Coordinating Ctr, Perry Point, MD USA. VA Boston Healthcare Syst, West Roxbury, MA USA. Greater Los Angeles VA Med Ctr, Los Angeles, CA USA. RP Almassi, GH (reprint author), Med Coll Wisconsin, 9200 Wisconsin Ave, Milwaukee, WI 53226 USA. EM halmassi@mcw.edu RI Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 FU Cooperative Studies Program of the Department of Veterans Affairs (CSP) [517]; Offices of Research and Development at the Zablocki VA Medical Center, Northport VA Medical Center; VA Eastern Colorado Healthcare System FX Special thanks are given to Ms Annette Wiseman and Ms Xiaoli (Shirley) Lu for their extraordinary assistance. This study was supported by the Cooperative Studies Program of the Department of Veterans Affairs (CSP #517) and by the Offices of Research and Development at the Zablocki VA Medical Center, Northport VA Medical Center, and the VA Eastern Colorado Healthcare System (Clinical Trials ID NCT00032630). NR 22 TC 3 Z9 5 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JAN PY 2015 VL 99 IS 1 BP 109 EP 114 DI 10.1016/j.athoracsur.2014.07.035 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AX6KI UT WOS:000347030800032 PM 25442992 ER PT J AU Stock, C Nathan, M Murray, R Rahbar, R Fynn-Thompson, F AF Stock, Cameron Nathan, Meena Murray, Ryan Rahbar, Reza Fynn-Thompson, Francis TI Modified End-to-End Anastomosis for the Treatment of Congenital Tracheal Stenosis With a Bridging Bronchus SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material ID RECONSTRUCTION; MANAGEMENT AB An infant with a ventricular septal defect; Vertebral anomalies, Anal atresia, Cardiac anomalies, Tracho Esophageal fistula (TEF), Renal anomalies, Limb anomalies syndrome; and tracheal stenosis with a bridging bronchus underwent repair of the ventricular septal defect and trachea-bronchial reconstruction at age 11 months. Herein we describe our surgical approach to resection of the bridging bronchus and a technique using a modified end-to-end tracheal anastomosis for the correction of this complex anomaly. (C) 2015 by The Society of Thoracic Surgeons C1 Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. [Fynn-Thompson, Francis] Boston Childrens Hosp, Dept Cardiac Surg, Boston, MA 02114 USA. Boston Childrens Hosp, Dept Otolaryngol & Commun Disorders, Boston, MA 02114 USA. RP Fynn-Thompson, F (reprint author), Boston Childrens Hosp, Dept Cardiac Surg, Boston, MA 02114 USA. EM fynn-thompson@cardio.chboston.org NR 6 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JAN PY 2015 VL 99 IS 1 BP 346 EP 348 DI 10.1016/j.athoracsur.2014.06.084 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AX6KI UT WOS:000347030800096 PM 25555968 ER PT J AU Fernandez, FG Falcoz, PE Kozower, BD Salati, M Wright, CD Brunelli, A AF Fernandez, Felix G. Falcoz, Pierre E. Kozower, Benjamin D. Salati, Michele Wright, Cameron D. Brunelli, Alessandro TI The Society of Thoracic Surgeons and The European Society of Thoracic Surgeons General Thoracic Surgery Databases: Joint Standardization of Variable Definitions and Terminology SO ANNALS OF THORACIC SURGERY LA English DT Article ID RISK-ADJUSTMENT MODEL; LUNG-CANCER; MAJOR MORBIDITY; STS DATABASE; PREDICTORS; MORTALITY; RESECTION; PERFORMANCE; LOBECTOMY; PROJECT AB The European Society of Thoracic Surgery (ESTS) and the Society of Thoracic Surgeons (STS) general thoracic surgery databases collect thoracic surgical data from Europe and North America, respectively. Their objectives are similar: to measure processes and outcomes so as to improve the quality of thoracic surgical care. Future collaboration between the two databases and their integration could generate significant new knowledge. However, important discrepancies exist in terminology and definitions between the two databases. The objective of this collaboration between the ESTS and STS is to identify important differences between databases and harmonize terminology and definitions to facilitate future endeavors. (C) 2015 by The Society of Thoracic Surgeons C1 Emory Univ, Atlanta, GA 30322 USA. Strasbourg Univ Hosp, Strasbourg, France. Univ Virginia, Charlottesville, VA USA. Osped Riuniti Ancona, Ancona, Italy. Massachusetts Gen Hosp, Boston, MA 02114 USA. St James Univ Hosp, Leeds LS9 7TF, W Yorkshire, England. RP Brunelli, A (reprint author), St James Univ Hosp, Dept Thorac Surg, Beckett St,Level 3, Leeds LS9 7TF, W Yorkshire, England. EM brunellialex@gmail.com RI falcoz, pierre-emmanuel/N-1239-2016; OI Brunelli, Alessandro/0000-0002-6505-1656 NR 19 TC 17 Z9 17 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JAN PY 2015 VL 99 IS 1 BP 368 EP 376 DI 10.1016/j.athoracsur.2014.05.104 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AX6KI UT WOS:000347030800100 PM 25555970 ER PT J AU Lusa, AL Amigues, I Kramer, HR Dam, TT Giles, JT AF Lusa, Amanda L. Amigues, Isabelle Kramer, Henry R. Dam, Thuy-Tien Giles, Jon T. TI Indicators of Walking Speed in Rheumatoid Arthritis: Relative Influence of Articular, Psychosocial, and Body Composition Characteristics SO ARTHRITIS CARE & RESEARCH LA English DT Article ID OLDER-ADULTS; KNEE ARTHROPLASTY; PHYSICAL-ACTIVITY; DISEASE-ACTIVITY; FOLLOW-UP; DISABILITY; ASSOCIATION; GAIT; WOMEN; MOBILITY AB Objective. To explore the contributions from and interactions between articular swelling and damage, psychosocial factors, and body composition characteristics on walking speed in rheumatoid arthritis (RA). Methods. RA patients underwent the timed 400-meter long-corridor walk. Demographics, self-reported levels of depressive symptoms and fatigue, RA characteristics, and body composition (using whole-body dual X-ray absorptiometry, and abdominal and thigh computed tomography) were assessed and their associations with walking speed explored. Results. A total of 132 RA patients had data for the 400-meter walk, among whom 107 (81%) completed the full 400 meters. Significant multivariable indicators of slower walking speed were older age, higher depression scores, higher reported pain and fatigue, higher swollen and replaced joint counts, higher cumulative prednisone exposure, nontreatment with disease-modifying antirheumatic drugs, and worse body composition. These features accounted for 60% of the modeled variability in walking speed. Among specific articular features, slower walking speed was primarily correlated with large/medium lower-extremity joint involvement. However, these articular features accounted for only 21% of the explainable variability in walking speed. Having any relevant articular characteristic was associated with a 20% lower walking speed among those with worse body composition (P < 0.001), compared with only a 6% lower speed among those with better body composition (P = 0.010 for interaction). Conclusion. Psychosocial factors and body composition are potentially reversible contributors to walking speed in RA. Relative to articular disease activity and damage, nonarticular indicators were collectively more potent indicators of an individual's mobility limitations. C1 [Lusa, Amanda L.; Amigues, Isabelle; Dam, Thuy-Tien; Giles, Jon T.] Columbia Univ, Coll Phys & Surg, New York, NY 10032 USA. [Kramer, Henry R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Giles, JT (reprint author), Columbia Univ, Coll Phys & Surg, Div Rheumatol, 630 West 168th St,Phys & Surg Bldg,Suite 10-445, New York, NY 10032 USA. EM jtg2122@columbia.edu FU NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases [AR-050026-01, 1K23-AR-054112-01]; Johns Hopkins Bayview Medical Center General Clinical Research Center [M01-RR-02719] FX Supported by the NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant AR-050026-01) and the Johns Hopkins Bayview Medical Center General Clinical Research Center (grant M01-RR-02719). Dr. Giles's work was supported by the NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant 1K23-AR-054112-01). NR 42 TC 3 Z9 3 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD JAN PY 2015 VL 67 IS 1 BP 21 EP 31 DI 10.1002/acr.22433 PG 11 WC Rheumatology SC Rheumatology GA AX4QS UT WOS:000346917200005 PM 25155859 ER PT J AU Baker, JF Long, J Ibrahim, S Leonard, MB Katz, P AF Baker, Joshua F. Long, Jin Ibrahim, Said Leonard, Mary B. Katz, Patricia TI Are Men at Greater Risk of Lean Mass Deficits in Rheumatoid Arthritis? SO ARTHRITIS CARE & RESEARCH LA English DT Article ID BODY-COMPOSITION; PHYSICAL-ACTIVITY; SEX-DIFFERENCES; DISEASE CHARACTERISTICS; REFERENCE VALUES; NECROSIS-FACTOR; SARCOPENIA; CACHEXIA; ASSOCIATION; OBESITY AB Objective. We aimed to determine if there were sex differences in lean body mass (LBM) in patients with rheumatoid arthritis (RA) when compared with sex-and race-specific National Health and Nutrition Examination Survey (NHANES) reference data, and to investigate the impact of sex differences in risk factors for LBM deficits. Methods. Dual x-ray absorptiometry measures of whole body LBM and appendicular LBM (arms and legs, appendicular lean mass [ALM]) were obtained on a total of 190 subjects from 2 independent cohorts (141 from San Francisco [SF], 49 from Philadelphia [PA]), expressed as indices adjusted for height (LBM index and ALM index, kg/m(2)), and converted to sex-and race-specific Z scores relative to age and based on NHANES data. Sarcopenia was defined using 4 different sex-specific definitions. Multivariable linear and logistic regression analyses adjusted for disease activity, disease duration, physical activity, anti-cyclic citrullinated peptide seropositivity, fat mass index, and glucocorticoid use. Results. While there were significant differences between the 2 cohorts, ALM index Z scores were significantly lower in men compared to women in both (SF: -1.43 versus -0.43, P < 0.0001; PA: -0.83 versus -0.06, P = 0.03). Observed sex differences were significant after adjustment in multivariable analyses within both cohorts. Odds of sarcopenia were 3 to 8 times greater in men in the SF cohort. Men in the PA cohort also had a higher, but nonsignificant, risk of sarcopenia. Conclusion. RA is associated with significant LBM deficits, with greater deficits observed in men. Future study may help elucidate the mechanisms driving greater deficits among men. C1 [Baker, Joshua F.; Ibrahim, Said] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Long, Jin; Leonard, Mary B.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Leonard, Mary B.] Univ Penn, Philadelphia, PA 19104 USA. [Katz, Patricia] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Katz, P (reprint author), Univ Calif San Francisco, 3333 Calif St,Suite 270, San Francisco, CA 94143 USA. EM patti.katz@ucsf.edu FU NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases [P60-AR-053308]; NIH/National Center for Research Resources [UL1-RR-024131]; Rosalind Russell Medical Research Center for Arthritis; University of Pennsylvania Clinical and Translational Research Center [UL1-RR-024134]; Veterans Affairs Clinical Science Research and Development Career Development Award [IK2 CX000955]; K24 Award from the NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases [K24-AR-055259, K24-DK-076808] FX Research at University of California, San Francisco was supported by the NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant P60-AR-053308), the NIH/National Center for Research Resources (grant UL1-RR-024131), and by the Rosalind Russell Medical Research Center for Arthritis. Research at University of Pennsylvania was supported by the University of Pennsylvania Clinical and Translational Research Center (UL1-RR-024134). Dr. Baker's work was supported by a Veterans Affairs Clinical Science Research and Development Career Development Award (IK2 CX000955). Drs. Ibrahim and Leonard's work was supported by a K24 Award (grants K24-AR-055259 and K24-DK-076808, respectively) from the NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases. NR 42 TC 6 Z9 6 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD JAN PY 2015 VL 67 IS 1 BP 112 EP 119 DI 10.1002/acr.22396 PG 8 WC Rheumatology SC Rheumatology GA AX4QS UT WOS:000346917200016 PM 25048740 ER PT J AU Forsythe, B Frank, RM Ahmed, M Verma, NN Cole, BJ Romeo, AA Provencher, MT Nho, SJ AF Forsythe, Brian Frank, Rachel M. Ahmed, Mohammed Verma, Nikhil N. Cole, Brian J. Romeo, Anthony A. Provencher, Matthew T. Nho, Shane J. TI Identification and Treatment of Existing Copathology in Anterior Shoulder Instability Repair SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article ID ROTATOR CUFF TEARS; ARTHROSCOPIC BANKART REPAIR; HILL-SACHS LESION; SUPERIOR LABRUM ANTERIOR; II SLAP LESIONS; GLENOHUMERAL INSTABILITY; MULTIDIRECTIONAL INSTABILITY; LONG HEAD; GLENOID LABRUM; POSTERIOR INSTABILITY AB Recurrent anterior instability is a common finding after traumatic glenohumeral dislocation in the young, athletic patient population. A variety of concomitant pathologies may be present in addition to the classic Bankart lesion, including glenoid bone loss; humeral head bone loss; rotator interval pathology; complex/large capsular injuries including humeral avulsions of the glenohumeral ligaments (HAGL lesions), SLAP tears, near circumferential labral tears, and anterior labral periosteal sleeve avulsions (ALPSA lesions); and rotator cuff tears. Normal anatomic variations masquerading as pathology also may be present. Recognition and treatment of these associated pathologies are necessary to improve function and symptoms of pain and to confer anterior shoulder stability. This review will focus on the history, physical examination findings, imaging findings, and recommended treatment options for common sources of copathology in anterior shoulder instability repair. C1 [Forsythe, Brian; Frank, Rachel M.; Ahmed, Mohammed; Verma, Nikhil N.; Cole, Brian J.; Romeo, Anthony A.; Nho, Shane J.] Rush Univ, Med Ctr, Dept Orthopaed Surg, Chicago, IL 60612 USA. [Provencher, Matthew T.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Forsythe, B (reprint author), Rush Univ, Med Ctr, Dept Orthopaed Surg, Midwest Orthopaed Rush, 1611 West Harrison St,Suite 400, Chicago, IL 60612 USA. EM brian.forsythe@rushortho.com OI Romeo, Anthony/0000-0003-4848-3411 FU Orthopaedic Research and Education Foundation; Pivot Medical; Stryker; Allosource FX The authors report the following potential conflict of interest or source of funding: B.F. receives support from Orthopaedic Research and Education Foundation. R.M.F., M.A., N.N.V., B.J.C., A.A.R., and M.T.P. receive support from Orthopaedic Research and Education Foundation. S.J.N. is a consultant and receives royalties from Pivot Medical, Stryker, and Ossur and receives research support from Pivot Medical, Stryker, and Allosource. NR 122 TC 9 Z9 9 U1 1 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-8063 EI 1526-3231 J9 ARTHROSCOPY JI Arthroscopy PD JAN PY 2015 VL 31 IS 1 BP 154 EP 166 DI 10.1016/j.arthro.2014.06.014 PG 13 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AX6KY UT WOS:000347032400029 PM 25200942 ER PT J AU Merseburger, AS Scher, HI Bellmunt, J Miller, K Mulders, PFA Stenzl, A Sternberg, CN Fizazi, K Hirmand, M Franks, B Haas, GP de Bono, J de Wit, R AF Merseburger, Axel S. Scher, Howard I. Bellmunt, Joaquim Miller, Kurt Mulders, Peter F. A. Stenzl, Arnulf Sternberg, Cora N. Fizazi, Karim Hirmand, Mohammad Franks, Billy Haas, Gabriel P. de Bono, Johann de Wit, Ronald TI Enzalutamide in European and North American men participating in the AFFIRM trial SO BJU INTERNATIONAL LA English DT Article DE androgen receptor inhibitor; enzalutamide; metastatic castration-resistant prostate cancer ID RESISTANT PROSTATE-CANCER; INCREASED SURVIVAL; MANAGEMENT; ASSOCIATION; ABIRATERONE; STRATEGIES; GUIDELINES; PATTERNS; OPTIONS AB Objective To explore any differences in efficacy and safety outcomes between European (EU) (n = 684) and North American (NA) (n = 395) patients in the AFFIRM trial (NCT00974311). Patients and Methods Phase III, double-blind, placebo-controlled, multinational AFFIRM trial in men with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel. Participants were randomly assigned in a 2: 1 ratio to receive oral enzalutamide 160 mg/day or placebo. The primary end point was overall survival (OS) in a post hoc analysis. Results Enzalutamide significantly improved OS compared with placebo in both EU and NA patients. The median OS in EU patients was longer than NA patients in both treatment groups. However, the relative treatment effect, expressed as hazard ratio and 95% confidence interval, was similar in both regions: 0.64 (0.50, 0.82) for EU and 0.63 (0.47, 0.83) for NA. Significant improvements in other end points further confirmed the benefit of enzalutamide over placebo in patients from both regions. The tolerability profile of enzalutamide was comparable between EU and NA patients, with fatigue and nausea the most common adverse events. Four EU patients (4/461 enzalutamide-treated, 0.87%) and one NA patient (1/263 enzalutamide-treated, 0.38%) had seizures. The difference in median OS was related in part to the timing of development of mCRPC and baseline demographics on study entry. Conclusion This post hoc exploratory analysis of the AFFIRM trial showed a consistent OS benefit for enzalutamide in men with mCRPC who had previously progressed on docetaxel in both NA- and EU-treated patients, although the median OS was higher in EU relative to NA patients. Efficacy benefits were consistent across end points, with a comparable safety profile in both regions. C1 [Merseburger, Axel S.] Hannover Med Sch, D-30623 Hannover, Germany. [Miller, Kurt] Charite, D-13353 Berlin, Germany. [Stenzl, Arnulf] Univ Klinikum Tubingen, Tubingen, Germany. [Scher, Howard I.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Bellmunt, Joaquim] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Hirmand, Mohammad] Medivation Inc, San Francisco, CA USA. [Franks, Billy; Haas, Gabriel P.] Astellas Sci & Med Affairs Inc, Northbrook, IL USA. [Mulders, Peter F. A.] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [de Wit, Ronald] Erasmus Univ, Med Ctr, Rotterdam, Netherlands. [Sternberg, Cora N.] San Camillo Forlanini Hosp, Rome, Italy. [Fizazi, Karim] Univ Paris Sud, Inst Gustave Roussy, Villejuif, France. [de Bono, Johann] Inst Canc Res, Sutton, Surrey, England. [de Bono, Johann] Royal Marsden NHS Fdn Trust, Sutton, Surrey, England. RP Merseburger, AS (reprint author), Hannover Med Sch MHH, Dept Urol & Urol Oncol, Carl Neuberg Str 1, D-30625 Hannover, Germany. EM merseburger.axel@mh-hannover.de RI Mulders, Peter/H-8076-2014 FU Astellas Pharma, Inc; Medivation, Inc. FX The authors had full access to the data and participated in reviewing and interpreting the data and paper. They would like to thank Karen Brayshaw, PhD, at Complete HealthVizion, for assistance with writing and revising the draft manuscript, based on detailed discussion and feedback from all authors. Writing assistance was funded by Astellas Pharma, Inc and Medivation, Inc. Primary responsibility for opinions, conclusions and interpretation of data lies with the authors. All authors read and approved the final version of this manuscript. NR 29 TC 3 Z9 3 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD JAN PY 2015 VL 115 IS 1 BP 41 EP 49 DI 10.1111/bju.12898 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA AX0OK UT WOS:000346651400012 PM 25123978 ER PT J AU Wecksler, AT Hwang, SH Liu, JY Wettersten, HI Morisseau, C Wu, J Weiss, RH Hammock, BD AF Wecksler, Aaron T. Hwang, Sung Hee Liu, Jun-Yan Wettersten, Hiromi I. Morisseau, Christophe Wu, Jian Weiss, Robert H. Hammock, Bruce D. TI Biological evaluation of a novel sorafenib analogue, t-CUPM SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Sorafenib analogue; Hepatoma cells; Kinase selectivity profile; Pharmacokinetics; Caspase-independent cell death; NCI-60 cell lines ID SOLUBLE EPOXIDE HYDROLASE; ADVANCED HEPATOCELLULAR-CARCINOMA; APOPTOSIS-INDUCING FACTOR; CELL-DEATH; MULTIKINASE INHIBITOR; EPOXYEICOSATRIENOIC ACIDS; RAF/MEK/ERK PATHWAY; GROWTH-FACTOR; CANCER-CELLS; ANGIOGENESIS AB Sorafenib (Nexavar(A (R))) is currently the only FDA-approved small molecule targeted therapy for advanced hepatocellular carcinoma. The use of structural analogues and derivatives of sorafenib has enabled the elucidation of critical targets and mechanism(s) of cell death for human cancer lines. We previously performed a structure-activity relationship study on a series of sorafenib analogues designed to investigate the inhibition overlap between the major targets of sorafenib Raf-1 kinase and VEGFR-2, and an enzyme shown to be a potent off-target of sorafenib, soluble epoxide hydrolase. In the current work, we present the biological data on our lead sorafenib analogue, t-CUPM, demonstrating that this analogue retains cytotoxicity similar to sorafenib in various human cancer cell lines and strongly inhibits growth in the NCI-60 cell line panel. Co-treatment with the pan-caspase inhibitor, Z-VAD-FMK, failed to rescue the cell viability responses of both sorafenib and t-CUPM, and immunofluorescence microscopy shows similar mitochondrial depolarization and apoptosis-inducing factor release for both compounds. These data suggest that both compounds induce a similar mechanism of caspase-independent apoptosis in hepatoma cells. In addition, t-CUPM displays anti-proliferative effects comparable to sorafenib as seen by a halt in G0/G1 in cell cycle progression. The structural difference between sorafenib and t-CUPM significantly reduces inhibitory spectrum of kinases by this analogue, and pharmacokinetic characterization demonstrates a 20-fold better oral bioavailability of t-CUPM than sorafenib in mice. Thus, t-CUPM may have the potential to reduce the adverse events observed from the multikinase inhibitory properties and the large dosing regimens of sorafenib. C1 [Wecksler, Aaron T.; Hwang, Sung Hee; Liu, Jun-Yan; Morisseau, Christophe; Hammock, Bruce D.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. [Wecksler, Aaron T.; Hwang, Sung Hee; Liu, Jun-Yan; Morisseau, Christophe; Wu, Jian; Weiss, Robert H.; Hammock, Bruce D.] Univ Calif Davis, Ctr Comprehens Canc, Sacramento, CA 95817 USA. [Wettersten, Hiromi I.; Weiss, Robert H.] Univ Calif Davis, Davis Med Ctr, Dept Internal Med, Div Nephrol, Sacramento, CA 95817 USA. [Wu, Jian] Univ Calif Davis, Davis Med Ctr, Dept Internal Med, Div Gastroenterol & Hepatol, Sacramento, CA 95817 USA. [Weiss, Robert H.] US Dept Vet Affairs, Med Ctr, Sacramento, CA 95655 USA. RP Hammock, BD (reprint author), Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. EM bdhammock@ucdavis.edu OI Wu, Jian/0000-0001-9933-7364 FU NIEHS [ES02710, P42 ES04699]; NIHLB [HL059699]; NIH [5UO1CA86402, 1R01CA135401-01A1, 1R01DK082690-01A1]; Medical Service of the US Department of Veterans' Affairs; National Institutes of Health [T32CA108459] FX We thank Dr. Michael Praddy of the MCB Imaging Facility for help with collecting and analyzing our immunohistochemical data on the Olympus FV100 laser point scanning microscope. Special thanks to Carol Oxford and the UCD Flow Cytometry Shared Resource facility for help with collecting and analyzing cell cycle data. This work was supported in part by NIEHS Grant ES02710, NIEHS Superfund Grant P42 ES04699, and NIHLB Grant HL059699 (all to B.D.H.). This work was also supported by NIH Grants 5UO1CA86402 (Early Detection Research Network), 1R01CA135401-01A1, and 1R01DK082690-01A1 (all to R.H.W.), and the Medical Service of the US Department of Veterans' Affairs (R.H.W.). A.T.W. was support by Award No. T32CA108459 from the National Institutes of Health. B.D.H. is a George and Judy Marcus senior fellow of the American Asthma Foundation. NR 39 TC 2 Z9 2 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 EI 1432-0843 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JAN PY 2015 VL 75 IS 1 BP 161 EP 171 DI 10.1007/s00280-014-2626-2 PG 11 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA AX8IL UT WOS:000347153200017 PM 25413440 ER PT J AU Schoenfeld, JD AF Schoenfeld, Jonathan D. TI Immunity in Head and Neck Cancer SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; EPSTEIN-BARR-VIRUS; TUMOR-INFILTRATING LYMPHOCYTES; CYTOTOXIC T-LYMPHOCYTES; HPV-ASSOCIATED HEAD; HUMAN-PAPILLOMAVIRUS; NASOPHARYNGEAL CARCINOMA; ADOPTIVE IMMUNOTHERAPY; TRANSPLANT RECIPIENTS; OROPHARYNGEAL CANCER AB Head and neck cancers are a diverse group of malignancies that includes an increasing number of virally mediated cancers in addition to tumors caused by tobacco and alcohol use. In both cases, tumor development is intimately related to the host immune system, and the status of an endogenous antitumor response is likely prognostic. Virally mediated cancers provide unique targets for preventive vaccines that generate immune responses directed against virus-associated antigens. Once head and neck tumors develop, they are commonly treated with surgery, radiotherapy, and/or chemotherapy. These treatments are associated with significant toxicities, and despite this, subgroups of patients respond poorly and are likely to relapse and die of their disease. Tumor immunotherapy may allow for improvements in both treatment-associated toxicity and outcome. In addition to providing specific targets for therapeutic vaccines and adoptive therapy, virally associated cancers may also be particularly dependent on immune checkpoints; therefore, immune checkpoint inhibitors are being actively tested for these diseases. Cancers that are not virally mediated may also respond to immunotherapies, and biomarkers that could predict response to immunotherapy irrespective of viral status are being evaluated. Multiple ongoing studies are testing benefits of immunotherapy in the management of metastatic squamous cell carcinoma of the head and neck. Early promising results pave the way for future studies that will expand testing to nonmetastatic diseases and other types of head and neck cancers. Prospects of combining various immunotherapies and more established treatments such as chemotherapy and radiotherapy are very intriguing and may provide synergistic benefits. (C) 2015 AACR. C1 [Schoenfeld, Jonathan D.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Schoenfeld, Jonathan D.] Dana Farber Canc Inst, Boston, MA 02114 USA. RP Schoenfeld, JD (reprint author), Dana Farber Canc Inst, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, 450 Brookline Ave,L2-57, Boston, MA 02114 USA. EM jdschoenfeld@partners.org FU Claudia Adams Barr Program for Innovative Cancer Research FX This study was supported by the Claudia Adams Barr Program for Innovative Cancer Research. NR 46 TC 15 Z9 15 U1 1 U2 6 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 JAN PY 2015 VL 3 IS 1 BP 12 EP 17 DI 10.1158/2326-6066.CIR-14-0205 PG 6 WC Oncology; Immunology SC Oncology; Immunology GA AY3AX UT WOS:000347458000002 PM 25568068 ER PT J AU Zhou, J Gupta, M Wu, XQ Yoon, C Giobbie-Hurder, A Hodi, FS AF Zhou, Jun Gupta, Meghna Wu, Xinqi Yoon, Charles Giobbie-Hurder, Anita Hodi, F. Stephen TI Immunity to the Vacuolar ATPase Complex Accessory Unit ATP6S1 in Patients with Malignant Melanoma SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID CD4(+) T-CELLS; METASTATIC MELANOMA; RESPONSES; CANCER; INHIBITOR; CD8(+); MEMORY AB The augmentation of high-titer antibodies to ATP6S1 is associated with favorable clinical outcomes in patients who received vaccination with autologous, irradiated tumor cells engineered to secrete GM-CSF and allogeneic bone marrow transplantation. Cellular immune responses to ATP6S1 are unknown. To define its role as an immune target, examination of cellular responses to ATP6S1 and immunity related to current therapies such as checkpoint blockade is needed. We used an overlapping peptide library representing the full-length ATP6S1 protein to screen for cellular responses from the peripheral blood of patients with stage III and IV melanoma. Reactive peptide pools were used to determine the individual peptide activity and epitopes. Recombinant ATP6S1 protein was used in an ELISA to assess potential correlation with humoral immune responses and changes in immunity related to CTLA-4 blockade with ipilimumab in these patients. We observed a broad array of CD4(+) and CD8(+) cellular responses against ATP6S1, including the identification of several MHC class I and II ATP6S1 epitopes. The generation of specific CD4(+) and cytotoxic T cells revealed potent functional capability elicited by ipilimumab treatment in patients with metastatic melanoma, which revealed potent functional capability, including cytokine production, proliferation responsiveness to melanoma cell lines, and tumor-cell killing. Furthermore, the augmented humoral immune responses to ATP6S1 as a function of ipilimumab treatment were associated with beneficial clinical outcomes. These results support the continued development of ATP6S1 as a biomarker and therapeutic target. (C) 2014 AACR. C1 [Zhou, Jun; Gupta, Meghna; Wu, Xinqi; Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Zhou, Jun; Gupta, Meghna; Wu, Xinqi; Yoon, Charles; Giobbie-Hurder, Anita; Hodi, F. Stephen] Harvard Univ, Sch Med, Boston, MA USA. [Zhou, Jun; Wu, Xinqi; Yoon, Charles; Giobbie-Hurder, Anita; Hodi, F. Stephen] Dana Farber Canc Inst, Melanoma Dis Ctr, Boston, MA 02115 USA. [Zhou, Jun; Giobbie-Hurder, Anita; Hodi, F. Stephen] Dana Farber Canc Inst, Ctr Immuno Oncol, Boston, MA 02115 USA. [Yoon, Charles] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Hodi, FS (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM stephen_hodi@dfci.harvard.edu FU Sharon Crowley Martin Memorial Fund for Melanoma Research at Dana-Farber Cancer Institute; Malcolm and Emily Mac Naught Fund for Melanoma Research at Dana-Farber Cancer Institute FX This work was supported in part by Sharon Crowley Martin Memorial Fund for Melanoma Research (to F.S. Hodi) and Malcolm and Emily Mac Naught Fund for Melanoma Research (to F.S. Hodi) at Dana-Farber Cancer Institute. NR 22 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 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD JAN PY 2015 VL 3 IS 1 BP 59 EP 67 DI 10.1158/2326-6066.CIR-14-0184 PG 9 WC Oncology; Immunology SC Oncology; Immunology GA AY3AX UT WOS:000347458000008 PM 25387894 ER PT J AU Behbod, B Sordillo, JE Hoffman, EB Datta, S Webb, TE Kwan, DL Kamel, JA Muilenberg, ML Scott, JA Chew, GL Platts-Mills, TAE Schwartz, J Coull, B Burge, H Gold, DR AF Behbod, B. Sordillo, J. E. Hoffman, E. B. Datta, S. Webb, T. E. Kwan, D. L. Kamel, J. A. Muilenberg, M. L. Scott, J. A. Chew, G. L. Platts-Mills, T. A. E. Schwartz, J. Coull, B. Burge, H. Gold, D. R. TI Asthma and allergy development: contrasting influences of yeasts and other fungal exposures SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Article DE allergy; asthma; children; damp; development; fungi; housing; indoor; infants; mould; outdoor; rhinitis; wheeze; yeast ID IN-HOUSE DUST; RESPIRATORY-TRACT ILLNESSES; DAY-CARE ATTENDANCE; EARLY-LIFE; CHILDHOOD ASTHMA; MOLD COMPONENTS; HOME CHARACTERISTICS; PARENTAL HISTORY; 1ST YEAR; CHILDREN AB BackgroundInfancy is a developmental stage with heightened susceptibility to environmental influences on the risk of chronic childhood disease. Few birth cohort studies have detailed measures of fungal diversity data in infants' bedrooms, limiting the potential to measure long-term associations of these complex exposures with development of asthma or allergy. ObjectiveWe evaluated the relation of home fungal levels in infancy to repeated measures of wheeze and development of asthma and rhinitis by age 13, and sensitization by age 12years. MethodsIn the Epidemiology of Home Allergens and Asthma prospective birth cohort study, we recruited 408 children with family history of allergic disease or asthma. When children were aged 2-3months, we measured culturable fungi in bedroom air and dust, and in outdoor air. Main outcomes included ascertainment of symptoms/disease onset by questionnaire from birth through age 13. We estimated hazard ratios and, for wheeze and sensitization, odds ratios for an interquartile increase in log-transformed fungal concentrations, adjusting for other outcome predictors and potential confounders. ResultsElevated levels of yeasts in bedroom floor dust were associated with reduced: i) wheeze at any age; ii) fungal sensitization; and iii) asthma development by age 13 (hazard ratio (HR)=0.86; 95% confidence interval (CI), [0.75 to 0.98]). Outdoor airborne Cladosporium and dustborne Aspergillus predicted increased rhinitis. Risk of fungal sensitization by age 12, in response to environmental Alternaria and Aspergillus, was elevated in children with a maternal history of fungal sensitization. Conclusions and Clinical RelevanceDespite the irritant and allergenic properties of fungi, early-life elevated dust yeast exposures or their components may be protective against allergy and asthma in children at risk for these outcomes. Ascertainment of fungal components associated with immunoprotective effects may have therapeutic relevance for asthma. C1 [Behbod, B.; Hoffman, E. B.; Schwartz, J.; Coull, B.; Burge, H.; Gold, D. R.] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Sordillo, J. E.; Datta, S.; Webb, T. E.; Kwan, D. L.; Kamel, J. A.; Gold, D. R.] Channing Labs, Boston, MA USA. [Hoffman, E. B.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Hoffman, E. B.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Muilenberg, M. L.] Univ Massachusetts, Amherst, MA 01003 USA. [Scott, J. A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Chew, G. L.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Platts-Mills, T. A. E.] Univ Virginia, Charlottesville, VA USA. RP Behbod, B (reprint author), Harvard Univ, Sch Publ Hlth, 401 Pk Dr West, Boston, MA 02215 USA. EM bbehbod@post.harvard.edu RI Scott, James/A-8598-2011 OI Scott, James/0000-0002-5073-0832 FU Harvard-Cyprus Endowment Scholarship; [R01 AI035786]; [EPA RD-83241601]; [AI-20565] FX The authors thank the families who have participated in this project. We also thank Professor Petros Koutrakis for his support as part of Behrooz Behbod's doctoral thesis committee. This manuscript has been supported by the following grants: R01 AI035786, EPA RD-83241601, and AI-20565. Dr Behbod's doctorate has been supported by the Harvard-Cyprus Endowment Scholarship. NR 60 TC 9 Z9 9 U1 0 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0954-7894 EI 1365-2222 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD JAN PY 2015 VL 45 IS 1 BP 154 EP 163 DI 10.1111/cea.12401 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA AX4OE UT WOS:000346910800018 PM 25200568 ER PT J AU Ring, DC AF Ring, David C. TI CORR Insights (R): What Is the Role of Mental Health in Primary Total Knee Arthroplasty? SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Editorial Material ID DEPRESSION; ATTRIBUTES; PAIN; TKA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ring, DC (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 9 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JAN PY 2015 VL 473 IS 1 BP 164 EP 165 DI 10.1007/s11999-014-3839-8 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AX4LA UT WOS:000346902900033 PM 25091228 ER PT J AU Overbeek, CL Nota, SPFT Jayakumar, P Hageman, MG Ring, D AF Overbeek, Celeste L. Nota, Sjoerd P. F. T. Jayakumar, Prakash Hageman, Michiel G. Ring, David TI The PROMIS Physical Function Correlates With the QuickDASH in Patients With Upper Extremity Illness SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID ITEM RESPONSE THEORY; REPORTED OUTCOMES; QUESTIONNAIRE LENGTH; HAND QUESTIONNAIRE; VALIDITY; PAIN; DEPRESSION; SHOULDER; DASH; ARM AB To assess disability more efficiently with less burden on the patient, the National Institutes of Health has developed the Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function-an instrument based on item response theory and using computer adaptive testing (CAT). Initially, upper and lower extremity disabilities were not separated and we were curious if the PROMIS Physical Function CAT could measure upper extremity disability and the Quick Disability of Arm, Shoulder and Hand (QuickDASH). We aimed to find correlation between the PROMIS Physical Function and the QuickDASH questionnaires in patients with upper extremity illness. Secondarily, we addressed whether the PROMIS Physical Function and QuickDASH correlate with the PROMIS Depression CAT and PROMIS Pain Interference CAT instruments. Finally, we assessed factors associated with QuickDASH and PROMIS Physical Function in multivariable analysis. A cohort of 93 outpatients with upper extremity illnesses completed the QuickDASH and three PROMIS CAT questionnaires: Physical Function, Pain Interference, and Depression. Pain intensity was measured with an 11-point ordinal measure (0-10 numeric rating scale). Correlation between PROMIS Physical Function and the QuickDASH was assessed. Factors that correlated with the PROMIS Physical Function and QuickDASH were assessed in multivariable regression analysis after initial bivariate analysis. There was a moderate correlation between the PROMIS Physical Function and the QuickDASH questionnaire (r = -0.55, p < 0.001). Greater disability as measured with the PROMIS and QuickDASH correlated most strongly with PROMIS Depression (r = -0.35, p < 0.001 and r = 0.34, p < 0.001 respectively) and Pain Interference (r = -0.51, p < 0.001 and r = 0.74, p < 0.001 respectively). The factors accounting for the variability in PROMIS scores are comparable to those for the QuickDASH except that the PROMIS Physical Function is influenced by other pain conditions while the QuickDASH is not. The PROMIS Physical Function instrument may be used as an upper extremity disability measure, as it correlates with the QuickDASH questionnaire, and both instruments are influenced most strongly by the degree to which pain interferes with achieving goals. Level III, diagnostic study. See the Instructions for Authors for a complete description of levels of evidence. C1 [Overbeek, Celeste L.; Nota, Sjoerd P. F. T.; Jayakumar, Prakash; Hageman, Michiel G.; Ring, David] Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Overbeek, Celeste L.; Nota, Sjoerd P. F. T.; Jayakumar, Prakash; Hageman, Michiel G.; Ring, David] Harvard Univ, Sch Med, Boston, MA USA. [Ring, David] Yawkey Ctr Outpatient Care, Orthopaed Associates, Boston, MA 02114 USA. RP Ring, D (reprint author), Yawkey Ctr Outpatient Care, Orthopaed Associates, Suite 2C,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org FU Anna Foundation\NOREF FX Anna Foundation vertical bar NOREF provided one of the authors (CLO) with financial support for her internship, which was not of influence on this research project. NR 42 TC 11 Z9 11 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JAN PY 2015 VL 473 IS 1 BP 311 EP 317 DI 10.1007/s11999-014-3840-2 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AX4LA UT WOS:000346902900057 PM 25099262 ER PT J AU Braden, A Overholser, J Fisher, L Ridley, J AF Braden, Abby Overholser, James Fisher, Lauren Ridley, Josephine TI Life Meaning Is Associated With Suicidal Ideation Among Depressed Veterans SO DEATH STUDIES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; POPULATION; HEALTH; RISK; PSYCHOTHERAPY; VALIDITY; SAMPLE; SCALE; SENSE AB Suicide is a major public health concern among U.S. veterans. Even when asked directly, veterans who die by suicide have been found to deny suicidal thoughts. Psychological assessment needs to go beyond the current risk factors and evaluate underlying factors that may increase suicide risk. In the present study, diagnostic interviews and self-report questionnaires were used to measure life meaning and suicidal ideation in a sample of 110 depressed veterans. Life meaning was significantly associated with suicidal ideation, even after accounting for depression and suicide history. Life meaning may be an important, previously ignored indicator of suicide risk. C1 [Braden, Abby] Univ Calif San Diego, Dept Pediat, San Diego, CA 92037 USA. [Overholser, James] Case Western Reserve Univ, Dept Psychol, Cleveland, OH 44106 USA. [Fisher, Lauren] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ridley, Josephine] Cleveland Wade Pk VA Med Ctr, Cleveland, OH USA. RP Braden, A (reprint author), Univ Calif San Diego, Ctr Hlth Eating & Act Res, Suite C-203, San Diego, CA 92037 USA. EM abraden@ucsd.edu NR 39 TC 1 Z9 1 U1 1 U2 13 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0748-1187 EI 1091-7683 J9 DEATH STUD JI Death Stud. PY 2015 VL 39 IS 1 BP 24 EP 29 DI 10.1080/07481187.2013.871604 PG 6 WC Psychology, Multidisciplinary; Social Issues; Social Sciences, Biomedical SC Psychology; Social Issues; Biomedical Social Sciences GA AX0OM UT WOS:000346651600004 PM 24932674 ER PT J AU Fisher, LB Overholser, JC Dieter, L AF Fisher, Lauren B. Overholser, James C. Dieter, Lesa TI Methods of Committing Suicide Among 2,347 People in Ohio SO DEATH STUDIES LA English DT Article ID DEATH REPORTING SYSTEM; COMPLETED SUICIDE; RISK-FACTORS; GENDER; PREVENTION; MORTALITY; PATTERNS AB The present study explored gender differences in suicidal methods, aiming to identify ways to improve our identification of individuals at risk for suicide. Preferred suicide methods vary by demographics; however, method-specific risk factors have not been consistently identified. All suicidal deaths (N=2,347) in a large urban county were identified over a 15-year period (1994-2008). The majority of men used shooting and hanging. In contrast, women relied on a variety of methods, including self-poisoning, shooting, hanging, and carbon monoxide poisoning. Significant demographic differences are evident among individuals who die by shooting and self-poisoning. C1 [Fisher, Lauren B.; Overholser, James C.; Dieter, Lesa] Case Western Reserve Univ, Dept Psychol, Cleveland, OH 44106 USA. RP Fisher, LB (reprint author), Massachusetts Gen Hosp, Dept Psychiat, One Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM lbfisher@partners.org FU NCRR NIH HHS [P20 RR017701]; NIGMS NIH HHS [P30 GM103328]; NIMH NIH HHS [MH67996, R01 MH067996] NR 25 TC 1 Z9 1 U1 1 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0748-1187 EI 1091-7683 J9 DEATH STUD JI Death Stud. PY 2015 VL 39 IS 1 BP 39 EP 43 DI 10.1080/07481187.2013.851130 PG 5 WC Psychology, Multidisciplinary; Social Issues; Social Sciences, Biomedical SC Psychology; Social Issues; Biomedical Social Sciences GA AX0OM UT WOS:000346651600006 PM 24932592 ER PT J AU Liang, P Xiong, JS Zhao, LW Xu, Y Zhao, JX Liu, Q AF Liang, Peng Xiong, Jinsheng Zhao, Liwei Xu, Ye Zhao, Jiaxin Liu, Qing TI Recombinant self-assembling 16-residue peptide nanofiber scaffolds for neuronal axonal outgrowth SO ENGINEERING IN LIFE SCIENCES LA English DT Article DE Axonal outgrowth; Neuron; Protein expression; Self-assembled nanofiber scaffold; Tissue engineering ID MARROW STROMAL CELLS; ESCHERICHIA-COLI; COMPLEMENTARY OLIGOPEPTIDE; NEURITE OUTGROWTH; IN-VITRO; REPAIR; REGENERATION; EXPRESSION; STRATEGIES; HYDROGELS AB Self-assembling peptides are considered a good biological scaffold for the repair of injured nervous system. In order to set up a stable system to produce the peptides at low cost, we used a gene recombinant expression method. The sequence of the peptide was devised to facilitate neural cell attachment and growth. The nucleotide sequence of the self-assembling peptide was designed, artificially synthesized, and inserted into the fusion protein vector pTYB2. After being transformed and expressed in Escherichia coli BL-21 (DE3) by means of the fusion protein, the soluble 16-residue peptide (named RAE16) was obtained by one-step chitin affinity chromatography. During cell culture, bone marrow stromal cells were fully embedded in the 3D environment of the peptide scaffolds. The MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) test indicated that bone marrow stromal cells cultured in RAE16 had the highest survival rate with the absorbance value of 0.7 at 7 days. Moreover, the cortical neural axons in the RAE16 group were longer (118.36 +/- 7.04 m) than in the other groups (p < 0.01). The recombinant peptide nanofiber scaffolds we designed provide a promising cell culture system for general molecular and cell biology studies and are useful as well for neural regeneration studies. C1 [Liang, Peng; Xiong, Jinsheng; Zhao, Liwei; Zhao, Jiaxin; Liu, Qing] Harbin Med Univ, Affiliated Tumor Hosp, Clin Coll 3, Dept Neurosurg, Harbin 150086, Peoples R China. [Xu, Ye] Harvard Med Univ, Dana Farber Canc Inst, Boston, MA USA. RP Liang, P (reprint author), Harbin Med Univ, Affiliated Tumor Hosp, Clin Coll 3, Dept Neurosurg, 150 Haping Rd, Harbin 150086, Peoples R China. EM liangpengd@yahoo.com NR 29 TC 2 Z9 2 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1618-0240 EI 1618-2863 J9 ENG LIFE SCI JI Eng. Life Sci. PD JAN PY 2015 VL 15 IS 1 BP 152 EP 158 DI 10.1002/elsc.201400116 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA AX9QF UT WOS:000347236300017 ER PT J AU Lincoln, AK Borg, R Delman, J AF Lincoln, Alisa K. Borg, Ryan Delman, Jonathan TI Developing a Community-Based Participatory Research Model to Engage Transition Age Youth Using Mental Health Service in Research SO FAMILY & COMMUNITY HEALTH LA English DT Article DE community-based participatory research; mental health services; transition age youth ID ADOLESCENTS; DELIVERY AB We present a model for the development and conduct of a community-based participatory research project with transition age youth (TAY) mental health service users. Community-based participatory research frameworks can facilitate equitable partnerships and meaningful inclusion but have not been fully drawn upon in mental health research. The model included TAY as trained research associates involved in every aspect of the research process. We describe the development of the project, creation of the research team, training, the design and conduct of the study, and challenges faced. The methods developed successfully provided support for the meaningful participation of TAY in the project. C1 [Lincoln, Alisa K.] Northeastern Univ, Boston, MA 02118 USA. [Borg, Ryan] Dana Farber Canc Inst, Boston, MA 02115 USA. [Delman, Jonathan] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. RP Lincoln, AK (reprint author), Northeastern Univ, 360 Huntington Ave,521 Holmes Hall, Boston, MA 02118 USA. EM al.lincoln@neu.edu FU NIMH NIH HHS [R21 MH083038, MH083038-01A1] NR 26 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0160-6379 EI 1550-5057 J9 FAM COMMUNITY HEALTH JI Fam. Community Health PD JAN-MAR PY 2015 VL 38 IS 1 BP 87 EP 97 DI 10.1097/FCH.0000000000000054 PG 11 WC Family Studies; Public, Environmental & Occupational Health SC Family Studies; Public, Environmental & Occupational Health GA AX1EY UT WOS:000346692000010 PM 25423247 ER PT J AU Karmon, AE Batsis, M Chavarro, JE Souter, I AF Karmon, Anatte E. Batsis, Maria Chavarro, Jorge E. Souter, Irene TI Preconceptional thyroid-stimulating hormone levels and outcomes of intrauterine insemination among euthyroid infertile women SO FERTILITY AND STERILITY LA English DT Article DE Thyroid-stimulating hormone; intrauterine insemination; infertility; spontaneous abortion; miscarriage ID IN-VITRO FERTILIZATION; REFERENCE INTERVALS; FEMALE REPRODUCTION; 1ST TRIMESTER; PREGNANCY; HYPOTHYROIDISM; DYSFUNCTION AB Objective: To evaluate differences in intrauterine insemination (IUI) outcomes among euthyroid women with preconceptional thyroid-stimulating hormone (TSH) values in the normal (0.4-2.4 mIU/L) and high-normal (2.5-4.9 mIU/L) ranges. Design: Cohort study. Setting: A single fertility center. Patient(s): A total of 1,477 women who underwent 4,064 IUI cycles between the years 2004 and 2012. Intervention(s): None. Main Outcome Measure(s): Live birth, clinical pregnancy, spontaneous abortion (SAB), and IUI cycle parameters. Result(s): Cycles were categorized into 4 groups based on preconceptional TSH values: 0.40-1.36 mIU/L; 1.37-1.86 mIU/L; 1.87-2.49 mIU/L; and 2.50-4.99 mIU/L. No statistically significant differences were found in IUI cycle parameters, clinical pregnancy rates, or live births per initiated cycle among the 4 TSH groups. However, preconceptional TSH was inversely related to SAB and positively related to live birth among women who achieved a clinical pregnancy. In this group of women, cycles with TSH values between 2.5 and 4.9 mIU/L were related to lower odds of SAB (odds ratio: 0.32; 95% confidence interval: 0.16-0.65) and higher odds of live birth (odds ratio: 2.80; 95% confidence interval: 1.43-5.48) compared with cycles among women in the lowest TSH group. Conclusion(s): Among euthyroid patients, preconceptional TSH values in the high-normal range (between 2.5 and 4.9 mIU/L) are not associated with adverse IUI outcomes. (C)2015 by American Society for Reproductive Medicine. C1 [Karmon, Anatte E.; Batsis, Maria; Souter, Irene] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Fertil Ctr,Dept Obstet & Gynecol,Reprod Endocrino, Boston, MA USA. [Chavarro, Jorge E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Karmon, AE (reprint author), Massachusetts Gen Hosp, Fertil Ctr, 55 Fruit St,Yawkey 10A, Boston, MA 02114 USA. EM akarmon@mgh.harvard.edu NR 22 TC 3 Z9 4 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD JAN PY 2015 VL 103 IS 1 BP 258 EP + DI 10.1016/j.fertnstert.2014.09.035 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA AX4OK UT WOS:000346911400043 PM 25439842 ER PT J AU Chang, C Goel, HL Gao, HJ Pursell, B Shultz, LD Greiner, DL Ingerpuu, S Patarroyo, M Cao, SL Lim, E Mao, JH Mckee, KK Yurchenco, PD Mercurio, AM AF Chang, Cheng Goel, Hira Lal Gao, Huijie Pursell, Bryan Shultz, Leonard D. Greiner, Dale L. Ingerpuu, Sulev Patarroyo, Manuel Cao, Shiliang Lim, Elgene Mao, Junhao Mckee, Karen Kulju Yurchenco, Peter D. Mercurio, Arthur M. TI A laminin 511 matrix is regulated by TAZ and functions as the ligand for the alpha 6B beta 1 integrin to sustain breast cancer stem cells SO GENES & DEVELOPMENT LA English DT Article DE TAZ; cancer stem cell; extracellular matrix; integrin; laminin ID PATHWAY; METASTASIS; YAP AB Understanding how the extracellular matrix impacts the function of cancer stem cells (CSCs) is a significant but poorly understood problem. We report that breast CSCs produce a laminin (LM) 511 matrix that promotes self-renewal and tumor initiation by engaging the alpha 6B beta 1 integrin and activating the Hippo transducer TAZ. Although TAZ is important for the function of breast CSCs, the mechanism is unknown. We observed that TAZ regulates the transcription of the alpha 5 subunit of LM511 and the formation of a LM511 matrix. These data establish a positive feedback loop involving TAZ and LM511 that contributes to stemness in breast cancer. C1 [Chang, Cheng; Goel, Hira Lal; Gao, Huijie; Pursell, Bryan; Mao, Junhao; Mercurio, Arthur M.] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA. [Shultz, Leonard D.] Jackson Lab, Bar Harbor, ME 04609 USA. [Greiner, Dale L.] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. [Ingerpuu, Sulev] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia. [Patarroyo, Manuel] Karolinska Inst, Dept Dent Med, SE-17177 Stockholm, Sweden. [Cao, Shiliang; Lim, Elgene] Dana Farber Canc Inst, Boston, MA 02284 USA. [Mckee, Karen Kulju; Yurchenco, Peter D.] Robert Wood Johnson Med Sch, Dept Pathol, Piscataway, NJ 08854 USA. RP Mercurio, AM (reprint author), Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA. EM hira.goel@umassmed.edu; arthur.mercurio@umassmed.edu OI Lim, Elgene/0000-0001-8065-8838 FU National Institutes of Health [CA168464]; Swedish Cancer Society FX National Institutes of Health grant CA168464 was the major support for this work. Support was also provided by a Swedish Cancer Society grant (to M.P.). NR 32 TC 18 Z9 20 U1 1 U2 9 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 JAN 1 PY 2015 VL 29 IS 1 BP 1 EP 6 DI 10.1101/gad.253682.114 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA AY1SK UT WOS:000347372100001 PM 25561492 ER PT J AU Blashill, AJ Williams, A Grogan, S Clark-Carter, D AF Blashill, Aaron J. Williams, Alison Grogan, Sarah Clark-Carter, David TI Negative Appearance Evaluation Is Associated With Skin Cancer Risk Behaviors Among American Men and Women SO HEALTH PSYCHOLOGY LA English DT Article DE skin cancer; appearance evaluation; UV exposure ID SUN PROTECTION INTENTIONS; BODY-IMAGE; SELF-ESTEEM; HEALTH; ADOLESCENTS; ATTITUDES AB Objective: The current study aimed to examine links between appearance evaluation and skin cancer risk behaviors in men and women. Method: Data (N = 1,535; men, n = 873; women, n = 662) were extracted from Wave 4 of the National Longitudinal Study of Adolescent Health, a nationally representative, longitudinal dataset of U.S. adolescents and young adults. Results: Skin cancer risk (i.e., number of hours spent outside for those with a history of severe sunburn and who were unlikely to use sunscreen) was significantly associated with participant gender, appearance evaluation, and their interaction. Both men and women who negatively evaluated their appearance were at significantly increased skin cancer risk, and this was particularly true for men. Conclusions: Negative appearance evaluation appears to be a correlate of engaging in behaviors that place individuals at risk of developing skin cancer. Future research may benefit from skin cancer prevention interventions that directly address appearance-based evaluations. C1 [Blashill, Aaron J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Blashill, Aaron J.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Williams, Alison; Clark-Carter, David] Staffordshire Univ, Dept Psychol Sport & Exercise, Stoke On Trent ST4 2DE, Staffs, England. [Grogan, Sarah] Manchester Metropolitan Univ, Dept Psychol, Manchester M15 6BH, Lancs, England. RP Blashill, AJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM ablashill@mgh.harvard.edu RI Grogan, Sarah/N-8664-2013 OI Grogan, Sarah/0000-0002-7510-765X FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [P01-HD31921]; National Institute of Mental Health of the National Institutes of Health [K23MH096647] FX This research uses data from Add Health, a program project directed by Kathleen Mullan Harris and designed by J. Richard Udry, Peter S. Bearman, and Kathleen Mullan Harris at the University of North Carolina at Chapel Hill, and funded by Grant P01-HD31921 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, with cooperative funding from 23 other federal agencies and foundations. Special acknowledgment is due Ronald R. Rindfuss and Barbara Entwisle for assistance in the original design. Information on how to obtain the Add Health data files is available on the Add Health website (http://www.cpc.unc.edu/addhealth). No direct support was received from Grant P01-HD31921 for this analysis. Research reported in this publication was supported by the National Institute of Mental Health of the National Institutes of Health under award number K23MH096647, awarded to Aaron Blashill. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 25 TC 4 Z9 4 U1 3 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 EI 1930-7810 J9 HEALTH PSYCHOL JI Health Psychol. PD JAN PY 2015 VL 34 IS 1 BP 93 EP 96 DI 10.1037/hea0000100 PG 4 WC Psychology, Clinical; Psychology SC Psychology GA AX4RY UT WOS:000346920200011 PM 25133823 ER PT J AU Parrinello, G Greene, SJ Torres, D Alderman, M Bonventre, JV Di Pasquale, P Gargani, L Nohria, A Fonarow, GC Vaduganathan, M Butler, J Paterna, S Stevenson, LW Gheorghiade, M AF Parrinello, Gaspare Greene, Stephen J. Torres, Daniele Alderman, Michael Bonventre, Joseph Vincent Di Pasquale, Pietro Gargani, Luna Nohria, Anju Fonarow, Gregg C. Vaduganathan, Muthiah Butler, Javed Paterna, Salvatore Stevenson, Lynne Warner Gheorghiade, Mihai TI Water and Sodium in Heart Failure: A Spotlight on Congestion SO HEART FAILURE REVIEWS LA English DT Article DE Heart failure; Congestion; Post-discharge; Fluid intake; Sodium diet; Management; Outcome ID RIGHT ATRIAL PRESSURE; INFERIOR VENA-CAVA; CARDIORENAL SYNDROME; RENAL-FUNCTION; EMERGENCY-DEPARTMENT; VENOUS CONGESTION; PROGNOSTIC VALUE; TUBULAR DAMAGE; KIDNEY INJURY; FOLLOW-UP AB Despite all available therapies, the rates of hospitalization and death from heart failure (HF) remain unacceptably high. The most common reasons for hospital admission are symptoms related to congestion. During hospitalization, most patients respond well to standard therapy and are discharged with significantly improved symptoms. Post-discharge, many patients receive diligent and frequent follow-up. However, rehospitalization rates remain high. One potential explanation is a persistent failure by clinicians to adequately manage congestion in the outpatient setting. The failure to successfully manage these patients post-discharge may represent an unmet need to improve the way congestion is both recognized and treated. A primary aim of future HF management may be to improve clinical surveillance to prevent and manage chronic fluid overload while simultaneously maximizing the use of evidence-based therapies with proven long-term benefit. Improvement in cardiac function is the ultimate goal and maintenance of a "dry" clinical profile is important to prevent hospital admission and improve prognosis. This paper focuses on methods for monitoring congestion, and strategies for water and sodium management in the context of the complex interplay between the cardiac and renal systems. A rationale for improving recognition and treatment of congestion is also proposed. C1 [Parrinello, Gaspare; Torres, Daniele; Paterna, Salvatore] Univ Palermo, Biomed Dept Internal & Specialty Med DiBiMIS, AOUP Paolo Giaccone, I-90127 Palermo, Italy. [Greene, Stephen J.; Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. [Alderman, Michael] Yeshiva Univ Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA. [Bonventre, Joseph Vincent] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Renal, Boston, MA 02115 USA. [Di Pasquale, Pietro] GF Ingrassia Hosp, Div Cardiol, Palermo, Italy. [Gargani, Luna] CNR, Inst Clin Physiol, Pisa, Italy. [Nohria, Anju; Stevenson, Lynne Warner] Harvard Univ, Brigham & Womens Hosp, Cardiovasc Div, Sch Med, Boston, MA 02115 USA. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Los Angeles, CA USA. [Vaduganathan, Muthiah] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. [Butler, Javed] Emory Univ, Div Cardiol, Atlanta, GA 30322 USA. RP Parrinello, G (reprint author), Univ Palermo, Biomed Dept Internal & Specialty Med DiBiMIS, AOUP Paolo Giaccone, Piazza Clin 2, I-90127 Palermo, Italy. EM gaspare.parrinello@unipa.it RI Gargani, Luna/C-6187-2015; OI Gargani, Luna/0000-0002-0716-453X; PARRINELLO, Gaspare/0000-0002-3594-7232 FU NIDDK NIH HHS [R37 DK039773] NR 61 TC 4 Z9 6 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1382-4147 EI 1573-7322 J9 HEART FAIL REV JI Heart Fail. Rev. PD JAN PY 2015 VL 20 IS 1 BP 13 EP 24 DI 10.1007/s10741-014-9438-7 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AY0JN UT WOS:000347283100002 PM 24942806 ER PT J AU McManus, DD Tanriverdi, K Lin, HH Esa, N Kinno, M Mandapati, D Tam, S Okike, ON Ellinor, PT Keaney, JF Donahue, JK Benjamin, EJ Freedman, JE AF McManus, David D. Tanriverdi, Kahraman Lin, Honghuang Esa, Nada Kinno, Menhel Mandapati, Divakar Tam, Stanley Okike, Okike N. Ellinor, Patrick T. Keaney, John F., Jr. Donahue, J. Kevin Benjamin, Emelia J. Freedman, Jane E. TI Plasma microRNAs are associated with atrial fibrillation and change after catheter ablation (the miRhythm study) SO HEART RHYTHM LA English DT Article DE Arial fibrillation; Epidemiology; Circulation; MicroRNA; Risk factor ID ACUTE MYOCARDIAL-INFARCTION; CIRCULATING MICRORNAS; HEART-FAILURE; POTENTIAL BIOMARKER; EXPRESSION; HYPERTROPHY; FIBROSIS; DISEASE; SIGNATURE AB BACKGROUND MicroRNAs (miRNAs) are associated with cardiovascular disease and control gene expression and are detectable in the circulation. OBJECTIVE The purpose of this study was to test the hypothesis that circulating miRNAs may be associated with atrial fibrillation (AF). METHODS Using aprospective study design powered to detect subtle differences in miRNAs, we quantified plasma expression of 86 miRNAs by high-throughput quantitative reverse transcriptase-polymerase chain reaction in 112 participants with AF and 99 without AF. To examine parallels between cardiac and plasma miRNA profiles, we quantified atrial tissue and plasma miRNA expression using quantitative reverse transcriptase-polymerase chain reaction in 31 participants undergoing surgery. We also explored the hypothesis that lower AF burden after ablation would be reflected in the circulating blood pool by examining change in plasma miRNAs after AF ablation (n = 47). RESULTS Mean age of the cohort was 59 years; 58% of participants were men. Plasma miRs-21 and 150 were 2-fold lower in participants with AF than in those without AF after adjustment (P <= .0006). Plasma levels of miRs-21 and 150 also were lower in participants with paroxysmal AF than in those with persistent AF (P < .05). Expression of miR-21, but not of miR-150, was lower in atrial tissue from patients with AF than in those without AF (P < .05). Plasma levels of miRs-21 and 150 increased 3-fold after AF ablation (P <= .0006). CONCLUSION Cardiac miRs-21 and 150 are known to regulate genes implicated in atrial remodeling. Our findings show associations between plasma miRs-21 and 150 and AF, suggesting that circulating miRNAs can provide in sights into cardiac gene regulation. C1 [McManus, David D.; Tanriverdi, Kahraman; Esa, Nada; Kinno, Menhel; Keaney, John F., Jr.; Donahue, J. Kevin; Freedman, Jane E.] Univ Massachusetts, Sch Med, Dept Med, Div Cardiol, Worcester, MA 01655 USA. [McManus, David D.; Lin, Honghuang; Benjamin, Emelia J.; Freedman, Jane E.] NHLBI, Framingham, MA USA. [McManus, David D.; Lin, Honghuang; Benjamin, Emelia J.; Freedman, Jane E.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [McManus, David D.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Div Epidemiol, Worcester, MA 01655 USA. [Lin, Honghuang] Boston Univ, Sch Med, Dept Med, Computat Biomed Sect, Boston, MA 02215 USA. [Mandapati, Divakar; Tam, Stanley; Okike, Okike N.] Univ Massachusetts, Sch Med, Dept Surg, Div Cardiothorac Surg, Worcester, MA 01655 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. RP McManus, DD (reprint author), Univ Massachusetts, Sch Med, 55 Lake Ave North, Worcester, MA 01655 USA. EM mcmanusd@ummhc.org OI Lin, Honghuang/0000-0003-3043-3942; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung, Blood Institute, National Institutes of Health [1U01HL105268-01, KL2RR031981, N01-HC 25195, 6R01-NS 17950, RFA-HL-12-008, 1R01 HL64753, R01 HL087201A, R01 HL076784, 1 R01 AG028321] FX This study was supported by Grants 1U01HL105268-01 and KL2RR031981 to Dr. McManus; N01-HC 25195, 6R01-NS 17950, RFA-HL-12-008, and 1R01 HL64753 to Dr. Freedman; R01 HL087201A to Drs. Freedman and Tanriverdi; and R01 HL076784 and 1 R01 AG028321 to Dr. Benjamin from the National Heart, Lung, Blood Institute, National Institutes of Health. NR 35 TC 16 Z9 19 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 EI 1556-3871 J9 HEART RHYTHM JI Heart Rhythm PD JAN PY 2015 VL 12 IS 1 BP 3 EP 10 DI 10.1016/j.hrthm.2014.09.050 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AX3RR UT WOS:000346857100007 PM 25257092 ER PT J AU Mattis, AN Song, GS Hitchner, K Kim, RY Lee, AY Sharma, AD Malato, Y McManus, MT Esau, CC Koller, E Koliwad, S Lim, LP Maher, JJ Raffai, RL Willenbring, H AF Mattis, Aras N. Song, Guisheng Hitchner, Kelly Kim, Roy Y. Lee, Andrew Y. Sharma, Amar D. Malato, Yann McManus, Michael T. Esau, Christine C. Koller, Erich Koliwad, Suneil Lim, Lee P. Maher, Jacquelyn J. Raffai, Robert L. Willenbring, Holger TI A Screen in Mice Uncovers Repression of Lipoprotein Lipase by MicroRNA-29a as a Mechanism for Lipid Distribution Away From the Liver SO HEPATOLOGY LA English DT Article ID FATTY LIVER; IN-VIVO; METABOLIC-DISORDERS; MOUSE-LIVER; EXPRESSION; HOMEOSTASIS; GENES; DISEASE; ATHEROSCLEROSIS; STEATOHEPATITIS AB Identification of microRNAs (miRNAs) that regulate lipid metabolism is important to advance the understanding and treatment of some of the most common human diseases. In the liver, a few key miRNAs have been reported that regulate lipid metabolism, but since many genes contribute to hepatic lipid metabolism, we hypothesized that other such miRNAs exist. To identify genes repressed by miRNAs in mature hepatocytes in vivo, we injected adult mice carrying floxed Dicer1 alleles with an adenoassociated viral vector expressing Cre recombinase specifically in hepatocytes. By inactivating Dicer in adult quiescent hepatocytes we avoided the hepatocyte injury and regeneration observed in previous mouse models of global miRNA deficiency in hepatocytes. Next, we combined gene and miRNA expression profiling to identify candidate gene/miRNA interactions involved in hepatic lipid metabolism and validated their function in vivo using antisense oligonucleotides. A candidate gene that emerged from our screen was lipoprotein lipase (Lpl), which encodes an enzyme that facilitates cellular uptake of lipids from the circulation. Unlike in energy-dependent cells like myocytes, LPL is normally repressed in adult hepatocytes. We identified miR-29a as the miRNA responsible for repressing LPL in hepatocytes, and found that decreasing hepatic miR-29a levels causes lipids to accumulate in mouse livers. Conclusion: Our screen suggests several new miRNAs are regulators of hepatic lipid metabolism. We show that one of these, miR-29a, contributes to physiological lipid distribution away from the liver and protects hepatocytes from steatosis. Our results, together with miR-29a's known antifibrotic effect, suggest miR-29a is a therapeutic target in fatty liver disease. (Hepatology 2015;61:141-152) C1 [Mattis, Aras N.; Song, Guisheng; Hitchner, Kelly; Lee, Andrew Y.; Sharma, Amar D.; Malato, Yann; Lim, Lee P.; Willenbring, Holger] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA. [Mattis, Aras N.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. [Mattis, Aras N.; Koliwad, Suneil; Maher, Jacquelyn J.; Willenbring, Holger] Univ Calif San Francisco, Ctr Liver, San Francisco, CA 94143 USA. [Kim, Roy Y.; Raffai, Robert L.] San Francisco VA Med Ctr, San Francisco, CA USA. [Malato, Yann; Willenbring, Holger] Univ Calif San Francisco, Dept Surg, Div Transplantat, San Francisco, CA 94143 USA. [McManus, Michael T.] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. [McManus, Michael T.; Koliwad, Suneil] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA. [Esau, Christine C.] Regulus Therapeut, San Diego, CA USA. [Koller, Erich] ISIS Pharmaceut, Carlsbad, CA 92008 USA. [Koliwad, Suneil] Univ Calif San Francisco, Dept Med, Div Endocrinol, San Francisco, CA 94143 USA. [Maher, Jacquelyn J.] Univ Calif San Francisco, Div Gastroenterol, Dept Med, San Francisco, CA 94143 USA. [Raffai, Robert L.] Univ Calif San Francisco, Div Vasc Surg, Dept Surg, San Francisco, CA 94143 USA. RP Willenbring, H (reprint author), Univ Calif San Francisco, 35 Med Ctr Way,Campus Box 0665, San Francisco, CA 94143 USA. EM willenbringh@stemcell.ucsf.edu RI Mattis, Aras/C-5558-2014 FU BLRD VA [I01 BX000532]; NHLBI NIH HHS [R01 HL089871]; NIDDK NIH HHS [L30 DK089949, P30 DK026743, DK063720, P30 DK063720, P30 DK26743, R01 DK068450, K08 DK098270]; NIGMS NIH HHS [R01 GM080783] NR 49 TC 13 Z9 13 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD JAN PY 2015 VL 61 IS 1 BP 141 EP 152 DI 10.1002/hep.27379 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AX6AF UT WOS:000347005100021 PM 25131933 ER PT J AU Maximos, M Bril, F Sanchez, PP Lomonaco, R Orsak, B Biernacki, D Suman, A Weber, M Cusi, K AF Maximos, Maryann Bril, Fernando Sanchez, Paola Portillo Lomonaco, Romina Orsak, Beverly Biernacki, Diane Suman, Amitabh Weber, Michelle Cusi, Kenneth TI The Role of Liver Fat and Insulin Resistance as Determinants of Plasma Aminotransferase Elevation in Nonalcoholic Fatty Liver Disease SO HEPATOLOGY LA English DT Article ID ALANINE-AMINOTRANSFERASE; CLINICAL-IMPLICATIONS; OBESE-PATIENTS; STEATOHEPATITIS; PREVALENCE; NAFLD; LIPOTOXICITY; METABOLISM; ETHNICITY; BIOPSIES AB Plasma aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) are usually increased in patients with nonalcoholic fatty liver disease (NAFLD). However, the factors behind their elevation remain unclear. The aim of this study was to assess the role of insulin resistance (IR) and liver triglyceride content in relation to histology in patients with NAFLD/nonalcoholic steatohepatitis (NASH) with normal or elevated ALT levels. To this end, we enrolled 440 patients, divided into three groups: no NAFLD (n=60); NAFLD with normal ALT (n=165); and NAFLD with elevated ALT (n=215). We measured: (1) liver fat by proton magnetic resonance spectroscopy (H-1-MRS); (2) severity of liver disease by biopsy (n=293); and (3) insulin sensitivity in liver, muscle, and adipose tissue by a euglycemic hyperinsulinemic clamp with 3-H-3-glucose. Patients with NAFLD and elevated ALT, even when well matched for body mass index to those with normal ALT, had worse adipose tissue insulin resistance (ATIR; P<0.0001), higher liver triglyceride content (P<0.0001), and lower plasma adiponectin (P<0.05), but no differences in hepatic insulin resistance. Similar results were found when only patients with NASH were compared: both ATIR (P<0.0001) and liver triglyceride content by H-1-MRS (P<0.0001) were worse in NASH with elevated ALT. Consistent with the H-1-MRS data, steatosis on liver biopsy was also significantly increased in patients with NASH and elevated ALT levels (P<0.0001). However, and most important, there were no differences in inflammation (P=0.62), ballooning (P=0.13), or fibrosis (P=0.12). Conclusion: In patients with NAFLD or NASH, ATIR (but not HIR) and liver triglyceride content are major factors in the elevation of plasma aminotransferase levels. Patients with normal versus elevated ALT had similar severity of NASH, suggesting that plasma aminotransferase levels are misleading parameters for guiding clinical management. (Hepatology 2015;61:153-160) C1 [Maximos, Maryann] Univ Florida, Div Pediat Gastroenterol Hepatol & Nutr, Gainesville, FL 32610 USA. [Maximos, Maryann; Bril, Fernando; Sanchez, Paola Portillo; Lomonaco, Romina; Biernacki, Diane; Suman, Amitabh; Weber, Michelle; Cusi, Kenneth] South Georgia Vet Hlth Syst, Malcom Randall VA Hosp North Florida, Gainesville, FL USA. [Bril, Fernando; Sanchez, Paola Portillo; Lomonaco, Romina; Biernacki, Diane; Cusi, Kenneth] Univ Florida, Div Endocrinol Diabet & Metab, Gainesville, FL 32610 USA. [Orsak, Beverly; Cusi, Kenneth] Univ Texas Hlth Sci Ctr San Antonio, Div Diabet, San Antonio, TX 78229 USA. [Orsak, Beverly; Cusi, Kenneth] Audie L Murphy Vet Adm Med Ctr, San Antonio, TX USA. RP Cusi, K (reprint author), Univ Florida, Div Endocrinol Diabet & Metab, 1600 Southwest Archer Rd,Room H-2, Gainesville, FL 32610 USA. EM Kenneth.Cusi@medicine.ufl.edu NR 26 TC 31 Z9 31 U1 2 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD JAN PY 2015 VL 61 IS 1 BP 153 EP 160 DI 10.1002/hep.27395 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AX6AF UT WOS:000347005100022 PM 25145475 ER PT J AU Bleier, BS Kocharyan, A Singleton, A Han, X AF Bleier, Benjamin S. Kocharyan, Armine Singleton, Amy Han, Xue TI Verapamil modulates interleukin-5 and interleukin-6 secretion in organotypic human sinonasal polyp explants SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE verapamil; calcium channel blocker; chronic rhinosinusitis; nasal polyps; explant ID CALCIUM-CHANNEL BLOCKERS; P-GLYCOPROTEIN; NASAL POLYPS; CHRONIC RHINOSINUSITIS; CYTOKINE PRODUCTION; INHIBITION; CELLS; ACTIVATION; PROTEIN AB BackgroundVerapamil is an L-type calcium channel blocker (CCB) that has been shown to have immunomodulatory properties in a variety of tissues. The goal of this study was determine whether verapamil is capable of regulating cytokine secretion in sinonasal polyps and to compare this effect to dexamethasone, an established immunosuppressive corticosteroid. MethodsThis was an institutional review board (IRB)-approved study in sinonasal polyp explants derived from 8 patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Polyps were incubated with dexamethasone or verapamil for 24 hours followed by an additional 24 hours with Staphylococcal enterotoxin B (SEB). Concentrations of secreted cytokines over each exposure period were determined by enzyme-linked immunosorbent assay (ELISA) and are expressed as a percent. Results were compared using a 2-tailed Student t test. ResultsThe percent of SEB-stimulated interleukin-5 (IL-5) secretion (mean standard deviation [SD], 339.94% +/- 315.48%) between the second and first treatment periods was significantly reduced following exposure to dexamethasone (74.08% +/- 26.77%, p < 0.05) and verapamil (119.99% +/- 69.32%, p < 0.05). The percent of SEB-stimulated IL-6 secretion (217.53% +/- 89.51%) was also significantly reduced following exposure to verapamil (148.82% +/- 79.15%, p < 0.05) but not dexamethasone (148.86% +/- 145.24%). Finally, the percent of SEB-stimulated thymic stromal lymphopoietin (TSLP) secretion (37.86% +/- 18.88%) demonstrated a nonsignificant trend toward reduction with both dexamethasone (31.15% +/- 35.28%) and verapamil (20.14% +/- 12.10%). ConclusionAlthough the mechanism has yet to be fully understood, L-type CCBs are capable of reducing inflammation in multiple tissues. Verapamil was specifically found to reduce airway goblet cell hyperplasia and eosinophilic infiltration in a murine asthma model. Our data support these findings suggesting that verapamil can modulate T-helper cell type 2 (Th2)-associated cytokine secretion in sinonasal polyp explants. This data points to a possible therapeutic role for CCBs in the management of CRSwNP. (C) 2014 ARS-AAOA, LLC. C1 [Bleier, Benjamin S.; Kocharyan, Armine] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Singleton, Amy; Han, Xue] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. RP Bleier, BS (reprint author), 243 Charles St, Boston, MA 02114 USA. EM benjamin_bleier@meei.harvard.edu NR 20 TC 8 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2042-6976 EI 2042-6984 J9 INT FORUM ALLERGY RH JI Int. Forum Allergy Rhinol. PD JAN PY 2015 VL 5 IS 1 BP 10 EP 13 DI 10.1002/alr.21436 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA AX9OK UT WOS:000347231600003 PM 25330767 ER PT J AU Ni, J Auriel, E Martinez-Ramirez, S Keil, B Reed, AK Fotiadis, P Gurol, EM Greenberg, SM Viswanathan, A AF Ni, Jun Auriel, Eithan Martinez-Ramirez, Sergi Keil, Boris Reed, Anne K. Fotiadis, Panagiotis Gurol, Edip Mahmut Greenberg, Steven M. Viswanathan, Anand TI Cortical Localization of Microbleeds in Cerebral Amyloid Angiopathy: An Ultra High-Field 7T MRI Study SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Cerebral amyloid angiopathy; cerebral microbleed; cortex; magnetic resonance imaging; ultra-high field ID BRAIN IMAGES; ROBUST; REGISTRATION; OPTIMIZATION; HEMORRHAGE; ACCURATE; BURDEN; FSL AB The extent of cortical involvement of cerebral amyloid angiopathy (CAA)-related microbleeds (CMBs) remains unclear. We examined five consecutive patients with probable CAA and three non-demented elderly subjects with ultra-high field 7T MRI, to identify the precise location of CAA-related CMBs. In five CAA patients, 169 of a total of 170 lobar CMBs were located in cortical areas on 7T MRI, while a precise cortical versus juxtacortical localization was unable to be determined for 50/76 CMBs observed by conventional MRI. 7T MRI demonstrates that nearly all lobar CMBs are located in cortex in CAA. C1 [Ni, Jun; Auriel, Eithan; Martinez-Ramirez, Sergi; Reed, Anne K.; Fotiadis, Panagiotis; Gurol, Edip Mahmut; Greenberg, Steven M.; Viswanathan, Anand] Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Dept Neurol, Boston, MA 02114 USA. [Ni, Jun; Auriel, Eithan; Martinez-Ramirez, Sergi; Reed, Anne K.; Fotiadis, Panagiotis; Gurol, Edip Mahmut; Greenberg, Steven M.; Viswanathan, Anand] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Ni, Jun] Beijing Union Med Coll Hosp, Dept Neurol, Beijing, Peoples R China. [Keil, Boris] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Viswanathan, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, J Kistler Stroke Res Ctr, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM aviswanathan1@partners.org RI Keil, Boris/P-1411-2014 FU NIH [K23AG028726-04, P50AG005134-30, 2R01 AG26484, 5R01AG026484-10, 5K23AG028726-05] FX All funding entities had no involvement in study design, data collection, analysis and interpretation, writing of the manuscript, and in the decision to submit for publication. The project described was supported by Grant Number: NIH grants K23AG028726-04, P50AG005134-30, 2R01 AG26484, 5R01AG026484-10, and 5K23AG028726-05. NR 21 TC 6 Z9 6 U1 2 U2 6 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 2015 VL 43 IS 4 BP 1325 EP 1330 DI 10.3233/JAD-140864 PG 6 WC Neurosciences SC Neurosciences & Neurology GA AX3RU UT WOS:000346857400021 PM 25171715 ER PT J AU Tsai, JN Uihlein, AV Burnett-Bowie, SAM Neer, RM Zhu, YL Derrico, N Lee, H Bouxsein, ML Leder, BZ AF Tsai, Joy N. Uihlein, Alexander V. Burnett-Bowie, Sherri-Ann M. Neer, Robert M. Zhu, Yuli Derrico, Nicholas Lee, Hang Bouxsein, Mary L. Leder, Benjamin Z. TI Comparative Effects of Teriparatide, Denosumab, and Combination Therapy on Peripheral Compartmental Bone Density, Microarchitecture, and Estimated Strength: the DATA-HRpQCT Study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE OSTEOPOROSIS; HIGH-RESOLUTION PERIPHERAL QUANTITATIVE COMPUTED TOMOGRAPHY; MICROARCHITECTURE; DENOSUMAB; TERIPARATIDE ID CORTICAL BONE; POSTMENOPAUSAL WOMEN; PARATHYROID-HORMONE; DISTAL RADIUS; HR-PQCT; INTRACORTICAL POROSITY; STRONTIUM RANELATE; ZOLEDRONIC ACID; TRABECULAR BONE; OSTEOPOROSIS AB Combined teriparatide and denosumab increases spine and hip bone mineral density more than either drug alone. The effect of this combination on skeletal microstructure and microarchitecture, however, is unknown. Because skeletal microstructure and microarchitecture are important components of skeletal integrity, we performed high-resolution peripheral quantitative computed tomography (HR-pQCT) assessments at the distal tibia and radius in postmenopausal osteoporotic women randomized to receive teriparatide 20 mu g daily (n=31), denosumab 60mg every 6 months (n=33), or both (n=30) for 12 months. In the teriparatide group, total volumetric bone mineral density (vBMD) did not change at either anatomic site but increased in both other groups at both sites. The increase in vBMD at the tibia was greater in the combination group (3.1 +/- 2.2%) than both the denosumab (2.2 +/- 1.9%) and teriparatide groups (-0.3 +/- 1.9%) (p<0.02 for both comparisons). Cortical vBMD decreased by 1.6 +/- 1.9% at the tibia and by 0.9 +/- 2.8% at the radius in the teriparatide group, whereas it increased in both other groups at both sites. Tibia cortical vBMD increased more in the combination group (1.5 +/- 1.5%) than both monotherapy groups (p<0.04 for both comparisons). Cortical thickness did not change in the teriparatide group but increased in both other groups. The increase in cortical thickness at the tibia was greater in the combination group (5.4 +/- 3.9%) than both monotherapy groups (p<0.01 for both comparisons). In the teriparatide group, radial cortical porosity increased by 20.9 +/- 37.6% and by 5.6 +/- 9.9% at the tibia but did not change in the other two groups. Bone stiffness and failure load, as estimated by finite element analysis, did not change in the teriparatide group but increased in the other two groups at both sites. Together, these findings suggest that the use of denosumab and teriparatide in combination improves HR-pQCT measures of bone quality more than either drug alone and may be of significant clinical benefit in the treatment of postmenopausal osteoporosis. (c) 2014 American Society for Bone and Mineral Research. C1 [Tsai, Joy N.; Uihlein, Alexander V.; Burnett-Bowie, Sherri-Ann M.; Neer, Robert M.; Zhu, Yuli; Derrico, Nicholas; Bouxsein, Mary L.; Leder, Benjamin Z.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Bouxsein, Mary L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Tsai, JN (reprint author), 50 Blossom St,Thier 1051, Boston, MA 02114 USA. EM jntsai@partners.org OI Burnett-Bowie, Sherri-Ann/0000-0002-0064-096X FU Harvard Clinical and Translational Science Center; National Center for Research Resources [1 UL1 RR025758-04]; Eli Lilly; Amgen FX We thank the study volunteers for their participation. This work is supported by the Harvard Clinical and Translational Science Center, the National Center for Research Resources (grant number 1 UL1 RR025758-04), Eli Lilly, and Amgen. NR 33 TC 27 Z9 28 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JAN PY 2015 VL 30 IS 1 BP 39 EP 45 DI 10.1002/jbmr.2315 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX4PR UT WOS:000346914600005 PM 25043459 ER PT J AU Fan, AP Govindarajan, ST Kinkel, RP Madigan, NK Nielsen, AS Benner, T Tinelli, E Rosen, BR Adalsteinsson, E Mainero, C AF Fan, Audrey P. Govindarajan, Sindhuja T. Kinkel, R. Philip Madigan, Nancy K. Nielsen, A. Scott Benner, Thomas Tinelli, Emanuele Rosen, Bruce R. Adalsteinsson, Elfar Mainero, Caterina TI Quantitative oxygen extraction fraction from 7-Tesla MRI phase: reproducibility and application in multiple sclerosis SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE brain imaging; energy metabolism; MRI; multiple sclerosis; neurodegeneration ID SURFACE-BASED ANALYSIS; CEREBRAL-BLOOD-FLOW; HUMAN-BRAIN; IN-VIVO; WHITE-MATTER; 7 T; METABOLISM; SUSCEPTIBILITY; SATURATION; LESIONS AB Quantitative oxygen extraction fraction (OEF) in cortical veins was studied in patients with multiple sclerosis (MS) and healthy subjects via magnetic resonance imaging (MRI) phase images at 7 Tesla (7 T). Flow-compensated, three-dimensional gradient-echo scans were acquired for absolute OEF quantification in 23 patients with MS and 14 age-matched controls. In patients, we collected T2*-weighted images for characterization of white matter, deep gray matter, and cortical lesions, and also assessed cognitive function. Variability of OEF across readers and scan sessions was evaluated in a subset of volunteers. OEF was averaged from 2 to 3 pial veins in the sensorimotor, parietal, and prefrontal cortical regions for each subject (total of similar to 10 vessels). We observed good reproducibility of mean OEF, with intraobserver coefficient of variation (COV) = 2.1%, interobserver COV = 5.2%, and scan-rescan COV = 5.9%. Patients exhibited a 3.4% reduction in cortical OEF relative to controls (P = 0.0025), which was not different across brain regions. Although oxygenation did not relate with measures of structural tissue damage, mean OEF correlated with a global measure of information processing speed. These findings suggest that cortical OEF from 7-T MRI phase is a reproducible metabolic biomarker that may be sensitive to different pathologic processes than structural MRI in patients with MS. C1 [Fan, Audrey P.; Rosen, Bruce R.; Adalsteinsson, Elfar] MIT, Cambridge, MA 02139 USA. [Fan, Audrey P.; Govindarajan, Sindhuja T.; Benner, Thomas; Rosen, Bruce R.; Adalsteinsson, Elfar; Mainero, Caterina] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Kinkel, R. Philip; Madigan, Nancy K.; Nielsen, A. Scott] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Kinkel, R. Philip; Madigan, Nancy K.; Rosen, Bruce R.; Mainero, Caterina] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Tinelli, Emanuele] Univ Roma La Sapienza, Dept Neurol & Psychiat, I-00185 Rome, Italy. RP Fan, AP (reprint author), Stanford Univ, Lucas Ctr Imaging, 1201 Welch Rd, Stanford, CA 94309 USA. EM auddie@stanford.edu FU National Science Foundation; Advanced Multimodal Neuroimaging Training Program; NIH [1R01-EB007942, 1R90-DA023427-01, 5R01-EB002066-18, 5P41-RR14075 08, 1U24-RR021382 04, T90-DA022759-01, P01-AT002048-05, 1UL1-RR02578-01, 1R01-EB006847, 2PO1-NS35611-11A1]; Biogen Idec; Harvard Medical School; NMSS [FP 1770A1, 4281-RG-A1]; Harvard Medical School SCSP [NH 1 KL2 RR025757-0]; Siemens Healthcare; Siemens-MIT Alliance FX APF receives research support from the National Science Foundation Graduate Research Fellowship, the Advanced Multimodal Neuroimaging Training Program, and the NIH (1R01-EB007942). STG has nothing to disclose. RPK is a scientific consultant for Biogen Idec, Teva, and Genzyme; serves as section editor of Neurology MedReviews; receives research support from Biogen Idec; receives partial salary support from Harvard Medical School; and receives support for his fellowship training program from the NMSS and support for research activities with the Accelerated Cure Project. NKM has nothing to disclose. ASN received fellowship training and financial support through the NMSS (FP 1770A1) and Harvard Medical School SCSP (NH 1 KL2 RR025757-0). TB served as a consultant for Siemens Medical Solutions and Bayer. ET has nothing to disclose. BRR has received honoraria for nonindustry sponsored activities and receives research support from the NIH (1R90-DA023427-01 (PI), 5R01-EB002066-18 (PI), 5P41-RR14075 08 (PI), 1U24-RR021382 04 (PI), T90-DA022759-01 (PI), P01-AT002048-05 (PI), and 1UL1-RR02578-01 (PI)). Dr Rosen is also affiliated with the Department of Meridian & Acupuncture, Collaborating Center for Traditional Medicine, East-West Medical Research Institute and School of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dondaemun-gu, Seoul 130-701, Republic of Korea. EA receives research support from Siemens Healthcare, the Siemens-MIT Alliance, and the NIH (1R01-EB007942 (PI) and 1R01-EB006847). CM served as a consultant for Biogen and receives research support from the NIH (2PO1-NS35611-11A1 (Investigator) and NMSS 4281-RG-A1 (PI)). NR 53 TC 5 Z9 5 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JAN PY 2015 VL 35 IS 1 BP 131 EP 139 DI 10.1038/jcbfm.2014.187 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA AY2AZ UT WOS:000347392200016 PM 25352043 ER PT J AU Mellish, JA Hindle, A Skinner, J Horning, M AF Mellish, Jo-Ann Hindle, Allyson Skinner, John Horning, Markus TI Heat loss in air of an Antarctic marine mammal, the Weddell seal SO JOURNAL OF COMPARATIVE PHYSIOLOGY B-BIOCHEMICAL SYSTEMIC AND ENVIRONMENTAL PHYSIOLOGY LA English DT Article DE Weddell seal; Surface temperature; Heat loss; Infrared imaging; Body condition ID LIONS EUMETOPIAS-JUBATUS; SURFACE-TEMPERATURE; PHOCA-VITULINA; MIROUNGA-ANGUSTIROSTRIS; HALICHOERUS-GRYPUS; SKIN TEMPERATURE; IR-THERMOGRAPHY; METABOLIC-RATE; BLUBBER DEPTH; MCMURDO SOUND AB The conflicting needs of homeostasis in air versus water complicate our understanding of thermoregulation in marine mammals. Large-scale modeling efforts directed at predicting the energetic impact of changing sea ice conditions on polar ecosystems require a better understanding of thermoregulation in air of free-ranging animals. We utilized infrared imaging as an indirect approach to determine surface temperatures of dry, hauled-out Weddell seals (Leptonychotes weddellii, n = 35) of varying age and body condition during the Antarctic summer. The study groups provided a fivefold range in body mass and a threefold range in blubber depth. Surface temperature (T (s)) did not vary by body region (head, shoulder, axilla, torso, hip, flippers). Average seal T (s) (mean 13.9 +/- A 11.2 A degrees C) was best described through a combination of the physical traits of body mass and environmental variables of ambient temperature T (air), and wind speed. Additional factors of ice temperature (T (ice)), relative humidity and cloud cover did not improve the model. Heat transfer model estimates suggested that radiation contributed 56.6 +/- A 7.7 % of total heat loss. Convection and conduction accounted for the remaining 15.7 +/- A 12.3 and 27.7 +/- A 9.3 %, respectively. Heat loss by radiation was primarily influenced by body mass and wind speed, whereas convective heat loss was influenced primarily by blubber depth and wind speed. Conductive heat loss was modeled largely as a function of physical traits of mass and blubber depth rather than any environmental covariates, and therefore was substantially higher in animals in leaner condition. C1 [Mellish, Jo-Ann] Univ Alaska Fairbanks, Sch Fisheries & Ocean Sci, Fairbanks, AK 99775 USA. [Mellish, Jo-Ann; Hindle, Allyson; Skinner, John] Alaska SeaLife Ctr, Seward, AK 99664 USA. [Hindle, Allyson] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA. [Horning, Markus] Oregon State Univ, Dept Fisheries & Wildlife, Newport, OR 97365 USA. [Horning, Markus] Oregon State Univ, Marine Mammal Inst, Newport, OR 97365 USA. RP Mellish, JA (reprint author), Alaska SeaLife Ctr, 301 Railway Ave,POB 1329, Seward, AK 99664 USA. EM joannm@alaskasealife.org OI Horning, Markus/0000-0001-6178-4935 FU National Science Foundation Office of Polar Programs Antarctic Organisms and Ecosystems [1043779] FX We would like to recognize the field efforts of R. Berngartt, R. Hill, H. Kaiser and M. Monnin, as well as the members of B-009 field team under J. Rotella and R. Garrott at the University of Montana. All work was conducted under Marine Mammal Protection Act 15748 and Antarctic Conservation Act 2012-003. This work was supported by the National Science Foundation Office of Polar Programs Antarctic Organisms and Ecosystems (Award 1043779). NR 36 TC 4 Z9 4 U1 6 U2 46 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0174-1578 EI 1432-136X J9 J COMP PHYSIOL B JI J. Comp. Physiol. B-Biochem. Syst. Environ. Physiol. PD JAN PY 2015 VL 185 IS 1 BP 143 EP 152 DI 10.1007/s00360-014-0868-2 PG 10 WC Physiology; Zoology SC Physiology; Zoology GA AX9WE UT WOS:000347249200013 PM 25378218 ER PT J AU Caccavale, LJ Nansel, TR Quick, V Lipsky, LM Laffel, LMB Mehta, SN AF Caccavale, Laura J. Nansel, Tonja R. Quick, Virginia Lipsky, Leah M. Laffel, Lori M. B. Mehta, Sanjeev N. TI Associations of Disordered Eating Behavior With the Family Diabetes Environment in Adolescents With Type 1 Diabetes SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE disordered eating; Type 1 diabetes; adolescents; family environment; diabetes management ID DIETARY-INTAKE; PREVALENCE; PATTERNS; GIRLS; ATTITUDES; MELLITUS; RISK AB Objective: To examine associations of disordered eating behaviors with aspects of the family eating and diabetes management environments among adolescents with Type 1 diabetes (T1D). Methods: Data were collected from 151 adolescents (mean age = 15.6 years) with T1D and their parents. Adolescents and parents completed self-report measures of the family eating environment (priority, atmosphere and structure/rules surrounding family meals, and the presence of restricted and special foods in the household) and diabetes family management environment (diabetes family conflict and responsibility sharing). Adolescents completed measures of parent modeling of healthy eating and disordered eating behaviors. Linear regression models were used to assess the relationship of disordered eating behaviors with aspects of the family eating and diabetes management environments. Results: In unadjusted models, adolescent, but not parent, report of aspects of the family eating environment was associated with adolescents' disordered eating behaviors. Both adolescent and parent report of diabetes family conflict were positively associated with disordered eating behaviors. The adjusted adolescent model including all family eating and diabetes management variables accounted for 20.8% of the variance in disordered eating behaviors (p < .001, R-2 = .208). Factors associated with greater risk of disordered eating included being female (beta = .168, p = .029), lower priority placed on family meals (beta = -.273, p = .003), less parental modeling of healthy eating (beta = -.197, p = .027), more food restrictions in the household beta = .223, (p = .005), and greater diabetes family conflict (beta = .195, p = .011). Conclusions: Findings suggest that aspects of the family eating environment and diabetes family conflict may represent important factors for disordered eating risk in adolescents with T1D. C1 [Caccavale, Laura J.] Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA. [Nansel, Tonja R.; Quick, Virginia; Lipsky, Leah M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, DHHS, Bethesda, MD USA. [Laffel, Lori M. B.; Mehta, Sanjeev N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect,Genet & Epid, Boston, MA 02115 USA. RP Caccavale, LJ (reprint author), Virginia Commonwealth Univ, Dept Psychol, Clin Psychol Program, 806 West Franklin St,POB 842018, Richmond, VA 23284 USA. EM caccavalelj@vcu.edu OI Nansel, Tonja/0000-0002-8298-7595 FU National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development [HHSN267200703434C] FX Supported by the intramural research program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, contract number HHSN267200703434C. NR 30 TC 0 Z9 0 U1 4 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0196-206X EI 1536-7312 J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD JAN PY 2015 VL 36 IS 1 BP 8 EP 13 PG 6 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA AX5SF UT WOS:000346986800002 PM 25493461 ER PT J AU Normandin, PA Sullivan, MM Goss, FR AF Normandin, Patricia A. Sullivan, Margaret M. Goss, Foster R. TI A 34-YEAR-OLD WOMAN WITH HEAVY VAGINAL BLEEDING SO JOURNAL OF EMERGENCY NURSING LA English DT Editorial Material C1 [Normandin, Patricia A.] Tufts Med Ctr, Boston, MA USA. [Normandin, Patricia A.] Northeastern Univ, Boston, MA USA. [Normandin, Patricia A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Normandin, Patricia A.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. [Normandin, Patricia A.] Boston Childrens Hosp, Boston, MA USA. [Sullivan, Margaret M.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Goss, Foster R.] Tufts Med Ctr, Dept Emergency Med, Boston, MA USA. RP Normandin, PA (reprint author), 7 Bowl Rd, Chelmsford, MA 01824 USA. EM pnormandinrn@aol.com NR 3 TC 0 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0099-1767 EI 1527-2966 J9 J EMERG NURS JI J. Emerg. Nurs. PD JAN PY 2015 VL 41 IS 1 BP 69 EP 70 DI 10.1016/j.jen.2014.10.003 PG 2 WC Emergency Medicine; Nursing SC Emergency Medicine; Nursing GA AX7PK UT WOS:000347107300022 PM 25459338 ER PT J AU Teunis, T Ring, D AF Teunis, Teun Ring, David TI Recovery From Distal Radius Fracture SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Letter ID REGIONAL PAIN SYNDROME; VITAMIN-C; WRIST FRACTURES; TRIAL C1 [Teunis, Teun; Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02138 USA. RP Teunis, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02138 USA. OI Ring, David/0000-0002-6506-4879 NR 6 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JAN PY 2015 VL 40 IS 1 BP 190 EP 190 DI 10.1016/j.jhsa.2014.10.049 PG 1 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AX8WI UT WOS:000347186000035 PM 25534842 ER PT J AU Carey, CD Gusenleitner, D Chapuy, B Kovach, AE Kluk, MJ Sun, HH Crossland, RE Bacon, CM Rand, V Dal Cin, P Le, LP Neuberg, D Sohani, AR Shipp, MA Monti, S Rodig, SJ AF Carey, Christopher D. Gusenleitner, Daniel Chapuy, Bjoern Kovach, Alexandra E. Kluk, Michael J. Sun, Heather H. Crossland, Rachel E. Bacon, Chris M. Rand, Vikki Dal Cin, Paola Le, Long P. Neuberg, Donna Sohani, Aliyah R. Shipp, Margaret A. Monti, Stefano Rodig, Scott J. TI Molecular Classification of MYC-Driven B-Cell Lymphomas by Targeted Gene Expression Profiling of Fixed Biopsy Specimens SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID RITUXIMAB PLUS CYCLOPHOSPHAMIDE; BURKITTS-LYMPHOMA; THERAPEUTIC TARGETS; PROTEIN EXPRESSION; TISSUE MICROARRAY; DISTINCT TYPES; MUTATIONS; BCL2; IDENTIFICATION; VINCRISTINE AB Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) are aggressive tumors of mature B cells that are distinguished by a combination of histomorphological, phenotypic, and genetic features. A subset of B-cell lymphomas, however, has one or more characteristics that overlap BL and DLBCL, and are categorized as B-cell lymphoma unclassifiable, with features intermediate between BL and DLBCL (BCL-U). Molecular analyses support the concept that there is a biological continuum between BL and DLBCL that includes variable activity of MYC, an oncoprotein once thought to be only associated with BL, but now recognized as a major predictor of survival among patients with DLBCL treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). We tested whether a targeted expression profiling panel could be used to categorize tumors as BL and DLBCL, resolve the molecular heterogeneity of BCL-U, and capture MYC activity using RNA from formalin-fixed, paraffin-embedded biopsy specimens. A diagnostic molecular classifier accurately predicted pathological diagnoses of BL and DLBCL, and provided more objective subclassification for a subset of BCL-U and genetic double-hit lymphomas as molecular BL or DLBCL. A molecular classifier of MYC activity correlated with MYC IHC and stratified patients with primary DLBCL treated with R-CHOP into high- and tow-risk groups. These results establish a framework for classifying and stratifying MYC-driven, aggressive, B-cell lymphomas on the basis of quantitative molecular profiting that is applicable to fixed biopsy specimens. C1 [Carey, Christopher D.; Kluk, Michael J.; Sun, Heather H.; Dal Cin, Paola; Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Carey, Christopher D.; Crossland, Rachel E.; Bacon, Chris M.; Rand, Vikki] Northern Inst Canc Res, Newcastle Upon Tyne, Tyne & Wear, England. [Gusenleitner, Daniel; Monti, Stefano] Boston Univ, Sch Med, Dept Computat Med, Boston, MA 02118 USA. [Chapuy, Bjoern; Shipp, Margaret A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Kovach, Alexandra E.; Le, Long P.; Sohani, Aliyah R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Rodig, SJ (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM srodig@partners.org OI Crossland, Rachel/0000-0001-6138-160X FU NCI NIH HHS [P01CA092625, P01 CA092625] NR 49 TC 6 Z9 6 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 EI 1943-7811 J9 J MOL DIAGN JI J. Mol. Diagn. PD JAN PY 2015 VL 17 IS 1 BP 19 EP 30 DI 10.1016/j.jmoldx.2014.08.006 PG 12 WC Pathology SC Pathology GA AX8EM UT WOS:000347143100005 PM 25468432 ER PT J AU Stapleton, CJ Walcott, BP Butler, WE Ogilvy, CS AF Stapleton, Christopher J. Walcott, Brian P. Butler, William E. Ogilvy, Christopher S. TI Neurological outcomes following intraprocedural rerupture during coil embolization of ruptured intracranial aneurysms SO JOURNAL OF NEUROSURGERY LA English DT Article DE aneurysm; coil embolization; endovascular neurosurgery; hydrocephalus; intraprocedural rupture; subarachnoid hemorrhage; vasospasm; vascular disorders ID SUBARACHNOID HEMORRHAGE; SYMPTOMATIC VASOSPASM; ENDOVASCULAR COILING; CEREBRAL ANEURYSMS; RANDOMIZED-TRIAL; BRAIN-INJURY; FISHER SCALE; HYDROCEPHALUS; MECHANISMS AB OBJECT Intraprocedural rerupture (IPR) of intracranial aneurysms during coil embolization is associated with significant periprocedural disability and death. However, whether this morbidity and mortality are secondary to an increased risk of vasospasm and hydrocephalus is unknown. The authors undertook this study to determine the in-hospitl and long-term neurological outcomes for patients with aneurysmal subarachnoid hemorrhage (SAH) treated with coil embolization who suffer aneurysm rerupture during treatment. METHODS The records of 156 patients admitted with SAH from previously untreated, ruptured, intracranial aneurysms and treated with endovascular coiling between January 2007 and January 2014 were retrospectively reviewed. Twelve patients (7.7%) experienced IPR during coil embolization. RESULTS Compared with the cohort of patients with uncomplicated coil embolization procedure, patients with aneurysm rerupture were more likely to require external ventricular drain (EVD) placement (91.7% vs 58.3%, p = 0.02) and postprocedural EVD placement (36.4% vs 7.1%, p = 0.01), to undergo permanent ventriculoperitoneal shunt placement (50.0% vs 18.8%, p = 0.02), to develop symptomatic vasospasm (50.0% vs 18.1%, p = 0.02), and to have longer lengths of hospital stay (median 21.5 days vs 15.0 days, p = 0.04). Admission Hunt and Hess, modified Fisher, and Barrow Neurological Institute grades did not differ between the 2 cohorts, nor did long-term functional neurological outcomes as assessed by the modified Rankin Scale. CONCLUSIONS Intraprocedural rerupture during coil embolization for ruptured intracranial aneurysms is associated with an increased risk of symptomatic vasospasm and need for temporary and permanent cerebrospinal fluid diversion for hydrocephalus. C1 [Stapleton, Christopher J.; Walcott, Brian P.; Butler, William E.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Stapleton, Christopher J.; Walcott, Brian P.; Butler, William E.; Ogilvy, Christopher S.] Harvard Univ, Sch Med, Boston, MA USA. [Ogilvy, Christopher S.] Beth Israel Deaconess Med Ctr, Dept Surg, Div Neurosurg, Boston, MA 02215 USA. [Ogilvy, Christopher S.] Beth Israel Deaconess Med Ctr, Brain Aneurysm Inst, Boston, MA 02215 USA. RP Stapleton, CJ (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White 502, Boston, MA 02114 USA. EM cstapleton@partners.org NR 24 TC 3 Z9 4 U1 0 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 EI 1933-0693 J9 J NEUROSURG JI J. Neurosurg. PD JAN PY 2015 VL 122 IS 1 BP 128 EP 135 DI 10.3171/2014.9.JNS14616 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA AX5DQ UT WOS:000346947600018 PM 25361491 ER PT J AU Jung, SY Je, Y Giovannucci, EL Rosner, B Ogino, S Cho, E AF Jung, Seungyoun Je, Youjin Giovannucci, Edward L. Rosner, Bernard Ogino, Shuji Cho, Eunyoung TI Derivation and Validation of Homocysteine Score in US Men and Women SO JOURNAL OF NUTRITION LA English DT Article DE homocysteine; one-carbon metabolism; diet; determinants; prediction; epidemiology ID PLASMA TOTAL HOMOCYSTEINE; ONE-CARBON METABOLISM; FOOD-FREQUENCY QUESTIONNAIRE; RENAL-CELL CANCER; LIFE-STYLE; HORDALAND HOMOCYSTEINE; CARDIOVASCULAR-DISEASE; BREAST-CANCER; PREMENOPAUSAL WOMEN; PHYSICAL-ACTIVITY AB Background: One-carbon metabolism, which is crucial in DNA synthesis and genomic stability, is an interrelated network of biochemical reactions involved in several dietary and lifestyle factors. The development of the homocysteine score using these factors may be useful to reflect the status of one-carbon metabolism in large epidemiologic studies without biologic samples to measure homocysteine directly. Objective: The aim of this study was to develop an homocysteine score that reflects one-carbon metabolism better than individual dietary or lifestyle factors. Methods: We divided 2023 participants with measured plasma total homocysteine data in the Nurses' Health Study and the Health Professionals Follow-Up Study into training (n = 1619) and testing (n = 404) subsets. Using multivariable linear regression, we selected lifestyle determinants of plasma homocysteine in the training set and derived the homocysteine score weighted by the 13 coefficient for each predictor. The validation of the homocysteine score was assessed using the plasma homocysteine in the independent samples of the training set. Results: In the training set, smoking, multivitamin use, and caffeine, alcohol, and dietary and supplemental folate intake were significant independent determinants of plasma homocysteine in multivariable linear regression (P <= 0.01) and were included in the derivation of the homocysteine score. The Pearson correlation of the homocysteine score with plasma homocysteine was 0.30 in the testing subset (P < 0.001). The homocysteine score was positively associated with the plasma homocysteine concentration in the testing subset and in an independent population of women; the mean difference of plasma homocysteine concentration between the extreme quintiles of homocysteine score ranged from 0.83 mu mol/L to 1.52 mu mol/L. Population misclassification either from the lowest quintile of plasma homocysteine into the highest quintile of the homocysteine score or from the highest quintile of plasma homocysteine into the lowest quintile of the homocysteine score was <= 12%. Conclusion: These data indicate that the homocysteine score may be used with relatively inexpensive and simple questionnaires to rank an individual's one-carbon metabolism status when homocysteine data are not available. C1 [Jung, Seungyoun; Rosner, Bernard; Cho, Eunyoung] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Jung, Seungyoun; Rosner, Bernard; Cho, Eunyoung] Harvard Univ, Sch Med, Boston, MA USA. [Je, Youjin] Kyung Hee Univ, Dept Food & Nutr, Seoul, South Korea. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward L.; Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Rosner, Bernard] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA USA. [Cho, Eunyoung] Brown Univ, Warren Alpert Med Sch, Dept Dermatol, Providence, RI 02912 USA. RP Cho, E (reprint author), Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. EM eunyoung.cho@channing.harvard.edu FU NIH [P01 CA87969, P01 CA55075, UM1 CA167552, R01 CA151993, R01 CA136950] FX Supported by NIH grants P01 CA87969 (to SE Hankinson), P01 CA55075 and UM1 CA167552 (to WC Willett), R01 CA151993 (to S Ogino), and R01 CA136950 (to E Cho) NR 61 TC 3 Z9 3 U1 1 U2 3 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 EI 1541-6100 J9 J NUTR JI J. Nutr. PD JAN PY 2015 VL 145 IS 1 BP 96 EP 104 DI 10.3945/jn.114.192716 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AY0BS UT WOS:000347263600014 PM 25527664 ER PT J AU Campbell, AP Rains, TM AF Campbell, Amy P. Rains, Tia M. TI Dietary Protein Is Important in the Practical Management of Prediabetes and Type 2 Diabetes SO JOURNAL OF NUTRITION LA English DT Article DE diabetes; prediabetes; protein; renal function; weight management ID IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE INTERVENTION; RANDOMIZED CONTROLLED-TRIAL; WEIGHT-LOSS; INSULIN-RESISTANCE; PREVENTION; MELLITUS; EXERCISE; PEOPLE; WOMEN AB Many misconceptions surround the role of dietary protein in the management of diabetes. Although dietary recommendations for managing diabetes have changed greatly over the centuries, recommended protein intake has remained relatively constant. Currently, recommendations for protein intake are based on individual assessment and the consideration of other health issues and implications, such as the extent of glycemic control, the presence of kidney disease, overweight and obesity, and the age of the patient. Two common misconceptions about dietary protein in diabetes management are that a certain amount of the protein consumed is converted into blood glucose and that consuming too much protein can lead to diabetic kidney disease. These misconceptions have been disproven. For many people with type 2 diabetes, aiming for 20-30% of total energy intake as protein is the goal. Exceptions may be for those individuals with impaired renal function. A protein intake of this amount can be beneficial by improving glycemic control, aiding in satiety and preservation of lean body mass during weight loss in those with both diabetes and prediabetes, and providing for the increased protein requirements of the older adult. Health care providers should discuss the role of dietary protein with their patients, reinforce sources of protein in the diet, and use simple but effective teaching tools, such as the plate method, to convey important nutrition messages. In addition, health care providers should recognize that persons with diabetes are attempting to manage many other aspects of their diabetes, including blood glucose monitoring, physical activity, taking of medication, risk reduction, and problem solving. C1 [Campbell, Amy P.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Rains, Tia M.] Egg Nutr Ctr, Park Ridge, IL USA. RP Campbell, AP (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM aepeterson@hotmail.com FU Egg Nutrition Center; American Egg Board FX Presented at the conference "Advances and Controversies in Clinical Nutrition," held in Washington, DC, 5-7 December 2013. The conference was sponsored by the Egg Nutrition Center and the American Egg Board The Supplement Coordinator for this supplement was Tia M Rains Supplement Coordinator disclosures: Tia M Rains is an employee of The Egg Nutrition Center/American Egg Board. The Session Chair was Mitch Kanter. This supplement is the responsibility of the Guest Editor to whom the Editor of The Journal of Nutrition has delegated supervision of both technical conformity to the published regulations of The Journal of Nutrition and general oversight of the scientific merit of each article. The Guest Editor for this supplement was Harry D Dawson. Guest Editor disclosure: no conflicts of interest. Publication costs for this supplement were defrayed in part by the payment of page charges. This publication must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact. The opinions expressed in this publication are those of the authors and are not attributable to the sponsors or the publisher, Editor, or Editorial Board of The Journal of Nutrition. NR 51 TC 3 Z9 3 U1 2 U2 22 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 EI 1541-6100 J9 J NUTR JI J. Nutr. PD JAN PY 2015 VL 145 IS 1 BP 164 EP 169 DI 10.3945/jn.114.194878 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AY0BS UT WOS:000347263600024 PM 25527675 ER PT J AU Johansen, KL Painter, P Delgado, C Doyle, J AF Johansen, Kirsten L. Painter, Patricia Delgado, Cynthia Doyle, Julie TI Characterization of Physical Activity and Sitting Time Among Patients on Hemodialysis Using a New Physical Activity Instrument SO JOURNAL OF RENAL NUTRITION LA English DT Article ID MORTALITY; ASSOCIATION; FRAILTY; COHORT; METAANALYSIS; SURVIVAL; DIALYSIS; DISEASE AB Objectives: Physical activity questionnaires usually focus on moderate to vigorous activities and may not accurately capture physical activity or variation in levels of activity among extremely inactive groups like dialysis patients. Design: Cross-sectional study. Setting: Three dialysis facilities in the San Francisco Bay Area. Subjects: Sixty-eight prevalent hemodialysis patients. Intervention: We administered a new physical activity questionnaire designed to capture activity in the lower end of the range, the Low Physical Activity Questionnaire (LoPAQ). Main Outcome Measure: Outcome measures were correlation with a validated physical activity questionnaire, the Minnesota Leisure Time Activity (LTA) questionnaire and with self-reported physical function (physical function score of the SF-36) and physical performance (gait speed, chair stand, balance, and short physical performance battery). We also determined whether patients who were frail or reported limitations in activities of daily living were less active on the LoPAQ. Results: Sixty-eight participants (mean age 59 +/- 14 years, 59% men) completed the study. Patients were inactive according to the LoPAQ, with a median (interquartile range) of 517 (204-1190) kcal/week of physical activity. Although activity from the LTA was lower than on the LoPAQ (411 [61-902] kcal/week), the difference was not statistically significant (P = .20), and results from the 2 instruments were strongly correlated (rho = 0.62, P < .001). In addition, higher physical activity measured by the LoPAQ was correlated with better self-reported functioning (rho = 0.64, P < .001), better performance on gait speed (rho = 0.32, P = .02), balance (rho = 0.45, P < .001), and chair rising (rho = -0.32, P = .03) tests and with higher short physical performance battery total score (rho = 0.51, P < .001). Frail patients and patients with activities of daily living limitations were less active than those who were not frail or limited. Conclusions: The LoPAQ performed similarly to the Minnesota LTA questionnaire in our cohort despite being shorter and easier to administer. (C) 2015 by the National Kidney Foundation, Inc. All rights reserved. C1 [Johansen, Kirsten L.; Delgado, Cynthia] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. [Johansen, Kirsten L.; Delgado, Cynthia] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Johansen, Kirsten L.; Doyle, Julie] Univ Calif San Francisco, US Renal Data Syst Nutr Special Studies Ctr, San Francisco, CA 94143 USA. [Painter, Patricia] Univ Utah, Dept Phys Therapy, Salt Lake City, UT USA. RP Johansen, KL (reprint author), San Francisco VA Med Ctr, Nephrol Sect, 111J,4150 Clement St, San Francisco, CA 94121 USA. EM kirsten.johansen@ucsf.edu FU National Institutes of Health [N01-DK-0005, K24 DK 085153] FX This work was supported by the National Institutes of Health (Contract N01-DK-0005 to K.L.J. and by K24 DK 085153 to K.L.J.). The interpretation and reporting of the data presented here are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the US government. NR 26 TC 4 Z9 4 U1 4 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1051-2276 EI 1532-8503 J9 J RENAL NUTR JI J. Renal Nutr. PD JAN PY 2015 VL 25 IS 1 BP 25 EP 30 DI 10.1053/j.jrn.2014.06.012 PG 6 WC Nutrition & Dietetics; Urology & Nephrology SC Nutrition & Dietetics; Urology & Nephrology GA AX4ON UT WOS:000346911700006 PM 25213326 ER PT J AU Koo, KH Nguyen, HV Andrasik, MP George, WH AF Koo, Kelly H. Nguyen, Hong V. Andrasik, Michele P. George, William H. TI The Cultural Context of Nondisclosure of Alcohol-Involved Acquaintance Rape Among Asian American College Women: A Qualitative Study SO JOURNAL OF SEX RESEARCH LA English DT Article ID SOCIAL SUPPORT; UNITED-STATES; HELP-SEEKING; STUDENTS; VICTIMS; SELF; ATTITUDES; SEXUALITY; IMMIGRANT; SEVERITY AB With high college enrollment and increasing alcohol use, Asian American (AA) college women may be at particular risk for experiencing alcohol-involved acquaintance rape. Although AA women have expressed the weakest intentions to report rape when compared to other ethnic groups, cultural factors influencing these intentions remain unexamined. Guided by grounded theory, 17 self-identified AA college women were interviewed about how the average AA college woman would respond to an alcohol-involved acquaintance rape. Despite awareness of benefits of disclosing rape, participants emphasized that nondisclosure would be the normative response. Three themes emerged from participants: institutional, sociocultural, and psychological contexts of nondisclosure. At an institutional level, nondisclosure referenced mental health and police services, which included Asian stereotypes and mistrust of police. Within a sociocultural context, rape nondisclosure focused on negative consequences on relationships with parents and, to a lesser extent, on friendships. Emotional avoidance and not labeling an acquaintance rape as rape were psychological strategies for rape nondisclosure. Participant's conceptualizations of mental and physical health concerns, specifically post-rape concerns, were framed within sociocultural/macrostructural contexts and may not match that of the more individualistic U.S. mainstream conceptualizations of health. Culturally sensitive rape education may be more effective in increasing rape prevention and support. C1 [Koo, Kelly H.; Nguyen, Hong V.; George, William H.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. [Andrasik, Michele P.] Univ Washington, Dept Psychiat, Fred Hutchinson Canc Res Ctr, HIV Vaccine Trials Network, Seattle, WA 98195 USA. RP Koo, KH (reprint author), San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. EM Kelly.Koo@va.gov FU NIAAA NIH HHS [1F31AA018237-01A1, 1R01AA016281-01A2] NR 47 TC 4 Z9 4 U1 3 U2 22 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0022-4499 EI 1559-8519 J9 J SEX RES JI J. Sex Res. PD JAN PY 2015 VL 52 IS 1 BP 55 EP 68 DI 10.1080/00224499.2013.826168 PG 14 WC Psychology, Clinical; Social Sciences, Interdisciplinary SC Psychology; Social Sciences - Other Topics GA AX0OL UT WOS:000346651500005 PM 24215167 ER PT J AU Lang, RM Badano, LP Mor-Avi, V Afilalo, J Armstrong, A Ernande, L Flachskampf, FA Foster, E Goldstein, SA Kuznetsova, T Lancellotti, P Muraru, D Picard, MH Rietzschel, ER Rudski, L Spencer, KT Tsang, W Voigt, JU AF Lang, Roberto M. Badano, Luigi P. Mor-Avi, Victor Afilalo, Jonathan Armstrong, Anderson Ernande, Laura Flachskampf, Frank A. Foster, Elyse Goldstein, Steven A. Kuznetsova, Tatiana Lancellotti, Patrizio Muraru, Denisa Picard, Michael H. Rietzschel, Ernst R. Rudski, Lawrence Spencer, Kirk T. Tsang, Wendy Voigt, Jens-Uwe TI Recommendations for Cardiac Chamber Quantification by Echocardiography in Adults: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Adult echocardiography; Transthoracic echocardiography; Ventricular function; Normal values ID LEFT ATRIAL VOLUME; AORTIC-VALVE IMPLANTATION; TIME 3-DIMENSIONAL ECHOCARDIOGRAPHY; LEFT-VENTRICULAR MASS; ACUTE MYOCARDIAL-INFARCTION; INFERIOR VENA-CAVA; MULTIDETECTOR COMPUTED-TOMOGRAPHY; GLOBAL LONGITUDINAL STRAIN; PATIENTS GREATER-THAN-OR-EQUAL-TO-65 YEARS; SPECKLE-TRACKING ECHOCARDIOGRAPHY AB The rapid technological developments of the past decade and the changes in echocardiographic practice brought about by these developments have resulted in the need for updated recommendations to the previously published guidelines for cardiac chamber quantification, which was the goal of the joint writing group assembled by the American Society of Echocardiography and the European Association of Cardiovascular Imaging. This document provides updated normal values for all four cardiac chambers, including three-dimensional echocardiography and myocardial deformation, when possible, on the basis of considerably larger numbers of normal subjects, compiled from multiple databases. In addition, this document attempts to eliminate several minor discrepancies that existed between previously published guidelines. C1 [Lang, Roberto M.; Mor-Avi, Victor; Spencer, Kirk T.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Badano, Luigi P.; Muraru, Denisa] Univ Padua, Padua, Italy. [Afilalo, Jonathan; Rudski, Lawrence] McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. [Armstrong, Anderson] Johns Hopkins Univ, Baltimore, MD USA. [Ernande, Laura] Hop Henri Mondor, INSERM, U955, F-94010 Creteil, France. [Ernande, Laura] Hop Henri Mondor, F-94010 Creteil, France. [Flachskampf, Frank A.] Uppsala Univ, Uppsala, Sweden. [Foster, Elyse] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Goldstein, Steven A.] Medstar Washington Hosp Ctr, Washington, DC USA. [Kuznetsova, Tatiana; Voigt, Jens-Uwe] Univ Hosp Leuven, Leuven, Belgium. [Lancellotti, Patrizio] Univ Liege Hosp, Liege, Belgium. [Picard, Michael H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Picard, Michael H.] Harvard Univ, Sch Med, Boston, MA USA. [Rietzschel, Ernst R.] Ghent Univ Hosp, Ghent, Belgium. [Tsang, Wendy] Univ Toronto, Toronto, ON, Canada. RP Lang, RM (reprint author), Amer Soc Echocardiog, 2100 Gateway Ctr Blvd,Suite 310, Morrisville, NC 27560 USA. EM ase@asecho.org OI Badano, Luigi/0000-0002-0379-3283; Armstrong, Anderson/0000-0003-3161-8922; Picard, Michael/0000-0002-9264-3243 FU GE Healthcare; Siemens; Esaote; Abbott Vascular Structural Heart FX The following authors reported relationships with one or more commercial interests: Luigi P. Badano, MD, PhD, FESC, received grants from GE Healthcare, Siemens, and Esaote and serves on the speakers' bureau for GE Healthcare. Elyse Foster, MD, FASE, received grant support from Abbott Vascular Structural Heart. Roberto M. Lang, MD, FASE, FESC, received grants from and serves on the speakers' bureau and advisory board for Philips Medical Systems. Denisa Muraru, MD, received research equipment from and served as a consultant for GE Healthcare. Lawrence Rudski, MD, FASE, holds stock in GE. NR 205 TC 695 Z9 722 U1 11 U2 31 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD JAN PY 2015 VL 28 IS 1 BP 1 EP U170 DI 10.1016/j.echo.2014.10.003 PG 53 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AX9WJ UT WOS:000347249700001 PM 25559473 ER PT J AU Porter, TR Shillcutt, SK Adams, MS Desjardins, G Glas, KE Olson, JJ Troughton, RW AF Porter, Thomas R. Shillcutt, Sasha K. Adams, Mark S. Desjardins, Georges Glas, Kathryn E. Olson, Joan J. Troughton, Richard W. TI Guidelines for the Use of Echocardiography as a Monitor for Therapeutic Intervention in Adults: A Report from the American Society of Echocardiography SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Echocardiography; Monitoring; Therapy; Doppler ID ORTHOTOPIC LIVER-TRANSPLANTATION; INTRAOPERATIVE TRANSESOPHAGEAL ECHOCARDIOGRAPHY; PULSED DOPPLER ECHOCARDIOGRAPHY; PERIOPERATIVE FLUID MANAGEMENT; PROSTHETIC VALVE THROMBOSIS; PULMONARY-ARTERY CATHETERS; VENTRICULAR ASSIST DEVICES; RANDOMIZED CLINICAL-TRIAL; AIR ASPIRATION CATHETER; TOTAL KNEE ARTHROPLASTY C1 [Porter, Thomas R.; Shillcutt, Sasha K.; Olson, Joan J.] Univ Nebraska, Med Ctr, Omaha, NE USA. [Adams, Mark S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Desjardins, Georges] Univ Utah, Salt Lake City, UT USA. [Glas, Kathryn E.] Emory Univ, Atlanta, GA 30322 USA. [Troughton, Richard W.] Univ Otago, Christchurch, New Zealand. RP Porter, TR (reprint author), Amer Soc Echocardiog, 2100 Gateway Ctr Blvd,Suite 310, Morrisville, NC 27560 USA. EM ase@asecho.org FU Philips Research North America; GE Healthcare; Astellas Pharma; Lantheus Medical Imaging; St. Jude Medical; Roche Diagnostics; Alere; Roche Pharmaceuticals FX The following authors reported relationships with one or more commercial interests: Thomas R. Porter, MD, FASE, has received research support from Philips Research North America, GE Healthcare, Astellas Pharma, and Lantheus Medical Imaging; Richard W. Troughton, MD, PhD, has served as a consultant for St. Jude Medical and received research support from St. Jude Medical, Roche Diagnostics, Alere, and Roche Pharmaceuticals. NR 95 TC 31 Z9 33 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD JAN PY 2015 VL 28 IS 1 BP 40 EP 56 DI 10.1016/j.echo.2014.09.009 PG 17 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AX9WJ UT WOS:000347249700002 PM 25559474 ER PT J AU Lilenbaum, R Samuels, M Wang, XF Kong, FM Janne, PA Masters, G Katragadda, S Hodgson, L Bogart, J Bradley, J Vokes, E AF Lilenbaum, Rogerio Samuels, Michael Wang, Xiaofei Kong, Feng Ming Jaenne, Pasi A. Masters, Gregory Katragadda, Sreedhar Hodgson, Lydia Bogart, Jeffrey Bradley, Jeffrey Vokes, Everett TI A Phase II Study of Induction Chemotherapy Followed by Thoracic Radiotherapy and Erlotinib in Poor-Risk Stage III Non-Small-Cell Lung Cancer Results of CALGB 30605 (Alliance)/RTOG 0972 (NRG) SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Poor risk; Stage III; NSCLC ID CHEMORADIOTHERAPY; TRIAL; GEFITINIB AB Introduction: Patients with stage III non-small-cell lung cancer and poor performance status and/or weight loss do not seem to benefit from standard therapy. Based on the preclinical interaction between epidermal growth factor receptor inhibitors and radiation, we designed a trial of induction chemotherapy followed by thoracic radiotherapy and concurrent erlotinib. Methods: Patients with poor-risk unresectable stage III non-smallcell lung cancer received two cycles of carboplatin at an AUC of 5 and nab-paclitaxel at 100 mg/m(2) on days 1 and 8 every 21 days, followed by erlotinib administered concurrently with thoracic radiotherapy. Maintenance was not permitted. Molecular analysis was performed in available specimens. Seventy-two eligible patients were required to test whether the 1-year survival rate was less than 50% or greater than or equal to 65% with approximately 90% power at a significance level of 0.10. Results: From March 2008 to October 2011, 78 patients were enrolled, three of whom were ineligible. The median age was 68 (range, 39-88) and 32% were aged greater than or equal to 75 years. Patients were evenly distributed between stages IIIA and IIIB and the majority had performance status 2. The overall response rate was 67% and the disease control rate was 93%. Treatment was well tolerated. The median PFS and OS were 11 and 17 months, respectively. The overall 12-month OS was 57%, which narrowly missed the pre-specified target for significance. Conclusions: Patients with poor-risk stage III non-small-cell lung cancer had better than expected outcomes with a regimen of induction carboplatin/nab-paclitaxel followed by thoracic radiotherapy and erlotinib. However, as per the statistical design, the 12-month OS was not sufficiently high to warrant further studies. C1 [Lilenbaum, Rogerio] Yale Canc Ctr, New Haven, CT 06519 USA. [Samuels, Michael] Univ Miami, Miami, FL USA. [Wang, Xiaofei; Hodgson, Lydia] Duke Univ, Alliance Stat & Data Ctr, Durham, NC USA. [Kong, Feng Ming] Univ Michigan, Ann Arbor, MI 48109 USA. [Jaenne, Pasi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Masters, Gregory] Christiana Care Hlth Syst, Wilmington, DE USA. [Katragadda, Sreedhar] Mem Hosp Martinsville, Martinsville, VA USA. [Bogart, Jeffrey] SUNY Upstate Univ, Syracuse, NY USA. [Bradley, Jeffrey] Washington Univ, Sch Med, St Louis, MO USA. [Vokes, Everett] Univ Chicago, Chicago, IL 60637 USA. RP Lilenbaum, R (reprint author), Yale Canc Ctr, 20 York St,NP 200, New Haven, CT 06519 USA. EM Rogerio.lilen-baum@yale.edu FU NCI NIH HHS [CA21060, U10 CA035421, CA59518, U10 CA180867, U10 CA045564, CA29165, CA47577, U10 CA041287, U10 CA059518, CA47559, CA33601, U10 CA021661, CA12046, U10 CA045808, CA03927, CA 37422, CA31946, CA45564, U10 CA045418, U10 CA047559, U10 CA003927, U10 CA077658, U10 CA032291, CA45418, CA35421, U10 CA037422, CA77658, U10 CA047577, CA41287, U10 CA033601, CA 21661, U10 CA031946, U10 CA180833, CA45808, U10 CA029511, U10 CA180882] NR 8 TC 11 Z9 13 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JAN PY 2015 VL 10 IS 1 BP 143 EP 147 DI 10.1097/JTO.0000000000000347 PG 5 WC Oncology; Respiratory System SC Oncology; Respiratory System GA AX5SC UT WOS:000346986500019 PM 25384173 ER PT J AU Morgensztern, D Campo, MJ Dahlberg, SE Doebele, RC Garon, E Gerber, DE Goldberg, SB Hammerman, PS Heist, RS Hensing, T Horn, L Ramalingam, SS Rudin, CM Salgia, R Sequist, LV Shaw, AT Simon, GR Somaiah, N Spigel, DR Wrangle, J Johnson, D Herbst, RS Bunn, P Govindan, R AF Morgensztern, Daniel Campo, Meghan J. Dahlberg, Suzanne E. Doebele, Robert C. Garon, Edward Gerber, David E. Goldberg, Sarah B. Hammerman, Peter S. Heist, Rebecca S. Hensing, Thomas Horn, Leora Ramalingam, Suresh S. Rudin, Charles M. Salgia, Ravi Sequist, Lecia V. Shaw, Alice T. Simon, George R. Somaiah, Neeta Spigel, David R. Wrangle, John Johnson, David Herbst, Roy S. Bunn, Paul Govindan, Ramaswamy TI Molecularly Targeted Therapies in Non-Small-Cell Lung Cancer Annual Update 2014 SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Non-small-cell lung cancer; Targeted therapies; Immunotherapy ID RECEPTOR TYROSINE KINASE; HEPATOCYTE GROWTH-FACTOR; CLINICAL-TRIAL DESIGN; PHASE-II TRIAL; RESISTANT GATEKEEPER MUTANT; ADVANCED SOLID MALIGNANCIES; HARBORING BRAF MUTATIONS; CHRONIC MYELOID-LEUKEMIA; ETV6-NTRK3 GENE FUSION; DNA-DAMAGING AGENTS AB There have been significant advances in the understanding of the biology and treatment of non-small-cell lung cancer (NSCLC) during the past few years. A number of molecularly targeted agents are in the clinic or in development for patients with advanced NSCLC. We are beginning to understand the mechanisms of acquired resistance after exposure to tyrosine kinase inhibitors in patients with oncogene addicted NSCLC. The advent of next-generation sequencing has enabled to study comprehensively genomic alterations in lung cancer. Finally, early results from immune checkpoint inhibitors are very encouraging. This review summarizes recent advances in the area of cancer genomics, targeted therapies, and immunotherapy. C1 [Morgensztern, Daniel; Govindan, Ramaswamy] Washington Univ, Sch Med, Dept Med Oncol, St Louis, MO 63110 USA. [Campo, Meghan J.; Hammerman, Peter S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Dahlberg, Suzanne E.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Doebele, Robert C.] Univ Colorado, Dept Med Oncol, Sch Med, Aurora, CO USA. [Doebele, Robert C.] Univ Colorado, Ctr Canc, Aurora, CO USA. [Garon, Edward] UCLA Santa Monica Hematol Oncol, Santa Monica, CA USA. [Gerber, David E.] Univ Texas SW Med Ctr Dallas, Harold C Simmons Canc Ctr, Div Hematol Oncol, Dallas, TX 75390 USA. [Goldberg, Sarah B.; Herbst, Roy S.] Yale Univ, Sch Med, Dept Med Oncol, New Haven, CT USA. [Goldberg, Sarah B.; Herbst, Roy S.] Ctr Canc, New Haven, CT USA. [Heist, Rebecca S.; Sequist, Lecia V.; Shaw, Alice T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Hensing, Thomas; Salgia, Ravi] Univ Chicago Med, Dept Oncol, Chicago, IL USA. [Horn, Leora] Vanderbilt Univ, Med Ctr, Div Hematol Oncol, Nashville, TN USA. [Ramalingam, Suresh S.] Emory Univ, Sch Med, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA USA. [Rudin, Charles M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Simon, George R.; Somaiah, Neeta] Med Univ S Carolina, Dept Hematol Oncol, Charleston, SC 29425 USA. [Spigel, David R.] Sarah Cannon Res Inst, Nashville, TN USA. [Wrangle, John] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Johnson, David] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Bunn, Paul] Univ Colorado, Sch Med, Div Med Oncol, Denver, CO USA. RP Govindan, R (reprint author), Washington Univ, Sch Med, Dept Med Oncol, St Louis, MO 63110 USA. EM rgovinda@dom.wustl.edu OI Rudin, Charles/0000-0001-5204-3465 FU NCATS NIH HHS [UL1 TR000142]; NCI NIH HHS [R21 CA170063, R01 CA182746, P30 CA006973, K12 CA167540, T32 CA009071, K23 CA149079] NR 328 TC 27 Z9 28 U1 3 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JAN PY 2015 VL 10 IS 1 SU 1 BP S1 EP S63 DI 10.1097/JTO.0000000000000405 PG 63 WC Oncology; Respiratory System SC Oncology; Respiratory System GA AX8JT UT WOS:000347156600001 PM 25535693 ER PT J AU Santry, HP Madore, JC Collins, CE Ayturk, MD Velmahos, GC Britt, LD Kiefe, CI AF Santry, Heena P. Madore, John C. Collins, Courtney E. Ayturk, M. Didem Velmahos, George C. Britt, L. D. Kiefe, Catarina I. TI Variations in the implementation of acute care surgery: Results from a national survey of university-affiliated hospitals SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Acute care surgery; emergency general surgery; practice variations; survey research ID GENERAL-SURGERY; EMERGENCY-SURGERY; TRAUMA-CENTER; SURGICAL EMERGENCIES; SERVICE; WORKFORCE; IMPACT; MODEL; APPENDICITIS; OUTCOMES AB BACKGROUND: To date, no studies have reported nationwide adoption of acute care surgery (ACS) or identified structural and/or process variations for the care of emergency general surgery (EGS) patients within such models. METHODS: We surveyed surgeons responsible for EGS coverage at University Health Systems Consortium hospitals using an eight-page postal/email questionnaire querying respondents on hospital and EGS structure/process measures. Survey responses were analyzed using descriptive statistics, univariate comparisons, and multivariable regression models. RESULTS: Of 319 potential respondents, 258 (81%) completed the surveys. A total of 81 hospitals (31%) had implemented ACS, while 134 (52%) had a traditional general surgeon on-call (GSOC) model. Thirty-eight hospitals (15%) had another model (hybrid). Larger-bed, university-based, teaching hospitals with Level 1 trauma center verification status located in urban areas were more likely to have adopted ACS. In multivariable modeling, hospital type, setting, and trauma center verification predicted ACS implementation. EGS processes of care varied, with 28% of the GSOC hospitals having block time versus 67% of the ACS hospitals (p < 0.0001), 45% of the GSOC hospitals providing ICU [intensive care unit] care to EGS patients in a surgical/trauma ICU versus 93% of the ACS hospitals (p < 0.0001), 5.7 +/- 3.2 surgeons sharing call at GSOC hospitals versus 7.9 +/- 2.3 surgeons at ACS hospitals (p < 0.0001), and 13% of the GSOC hospitals requiring in-house EGS call versus 75% of the ACS hospitals (p < 0.0001). Among ACS hospitals, there were variations in patient cohorting (EGS patients alone, 25%; EGS + trauma, 21%; EGS + elective, 17%; and EGS + trauma + elective, 30%), data collection (26% had prospective EGS registries), patient hand-offs (56% had attending surgeon presence), and call responsibilities (averaging 4.8 +/- 1.3 calls per month, with 60% providing extra call stipend and 40% with no postcall clinical duties). CONCLUSION: The potential of the ACS on the national crisis in access to EGS care is not fully met. Variations in EGS processes of care among adopters of ACS suggest that standardized criteria for ACS implementation, much like trauma center verification criteria, may be beneficial. Copyright (c) 2015 Wolters Kluwer Health, Inc. All rights reserved. C1 [Santry, Heena P.; Madore, John C.; Collins, Courtney E.; Ayturk, M. Didem] Univ Massachusetts, Sch Med, Dept Surg, Worcester, MA USA. [Santry, Heena P.; Kiefe, Catarina I.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Velmahos, George C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Britt, L. D.] Eastern Virginia Med Sch, Dept Surg, Norfolk, VA 23501 USA. RP Santry, HP (reprint author), Dept Surg, Room S3-731,55 Lake Ave North, Worcester, MA 01655 USA. EM Heena.Santry@umassmemorial.org FU National Institutes of Health [UL1RR031982, 1KL2RR031981-01 (02), 8KL2TR000160-03] FX H.P.S. receives partial salary support from a grant from the National Institutes of Health (UL1RR031982, 1KL2RR031981-01 (02), 8KL2TR000160-03). NR 40 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD JAN PY 2015 VL 78 IS 1 BP 60 EP 67 DI 10.1097/TA.0000000000000492 PG 8 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA AX3OB UT WOS:000346847500014 PM 25539204 ER PT J AU Fox, N Schwartz, D Salazar, JH Haut, ER Dahm, P Black, JH Brakenridge, SC Como, JJ Hendershot, K King, DR Maung, AA Moorman, ML Nagy, K Petrey, LB Tesoriero, R Scalea, TM Fabian, TC AF Fox, Nicole Schwartz, Diane Salazar, Jose H. Haut, Elliott R. Dahm, Philipp Black, James H. Brakenridge, Scott C. Como, John J. Hendershot, Kimberly King, David R. Maung, Adrian A. Moorman, Matthew L. Nagy, Kimberly Petrey, Laura B. Tesoriero, Ronald Scalea, Thomas M. Fabian, Timothy C. TI Evaluation and management of blunt traumatic aortic injury: A practice management guideline from the Eastern Association for the Surgery of Trauma SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Blunt aortic injury; traumatic aortic injury; blunt aortic trauma ID CHEST COMPUTED-TOMOGRAPHY; DESCENDING THORACIC AORTA; ENDOVASCULAR STENT-GRAFTS; SINGLE-CENTER EXPERIENCE; OPEN REPAIR; DELAYED REPAIR; AMERICAN-ASSOCIATION; CONTAINED RUPTURE; OPERATIVE REPAIR; SURGICAL REPAIR AB BACKGROUND: Blunt traumatic aortic injury (BTAI) is the second most common cause of death in trauma patients. Eighty percent of patients with BTAI will die before reaching a trauma center. The issues of how to diagnose, treat, and manage BTAI were first addressed by the Eastern Association for the Surgery of Trauma (EAST) in the practice management guidelines on this topic published in 2000. Since that time, there have been advances in the management of BTAI. As a result, the EAST guidelines committee decided to develop updated guidelines for this topic using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework recently adopted by EAST. METHODS: A systematic review of the MEDLINE database using PubMed was performed. The search retrieved English language articles regarding BTAI from 1998 to 2013. Letters to the editor, case reports, book chapters, and review articles were excluded. Topics of investigation included imaging to diagnose BTAI, type of operative repair, and timing of operative repair. RESULTS: Sixty articles were identified. Of these, 51 articles were selected to construct the guidelines. CONCLUSION: There have been changes in practice since the publication of the previous guidelines in 2000. Computed tomography of the chest with intravenous contrast is strongly recommended to diagnose clinically significant BTAI. Endovascular repair is strongly recommended for patients without contraindications. Delayed repair of BTAI is suggested, with the stipulation that effective blood pressure control must be used in these patients. Copyright (c) 2015 Wolters Kluwer Health, Inc. All rights reserved. C1 [Fox, Nicole] Rowan Univ, Cooper Univ Hosp, Cooper Med Sch, Dept Surg, Camden, NJ USA. [Schwartz, Diane] Johns Hopkins Bayview Med Ctr, Dept Surg, Baltimore, MD USA. [Haut, Elliott R.] Johns Hopkins Sch Med, Dept Surg, Baltimore, MD USA. [Black, James H.] Johns Hopkins Univ Hosp, Dept Vasc Surg & Endovasc Therapy, Baltimore, MD 21287 USA. [Black, James H.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Tesoriero, Ronald; Scalea, Thomas M.] Univ Maryland, Sch Med, R Adams Cowley Shock Trauma Ctr, Dept Surg, Baltimore, MD 21201 USA. [Dahm, Philipp] Univ Florida, Coll Med, Malcom Randall VAMC, Dept Urol, Gainesville, FL USA. [Brakenridge, Scott C.] Univ Florida, Hlth Sci Ctr, Dept Surg, UF Hlth Shands Hosp, Gainesville, FL USA. [Como, John J.] Metrohlth Med Ctr, Dept Surg, Cleveland, OH 44109 USA. [Moorman, Matthew L.] Cleveland Clin, Lerner Coll Med, Div Acute Care Surg, Cleveland, OH 44106 USA. Wright State Univ, Boonshoft Sch Med, Dept Surg, Dayton, OH 45435 USA. [King, David R.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Maung, Adrian A.] Yale Univ, Sch Med, Dept Surg, New Haven, CT 06510 USA. [Nagy, Kimberly] Stroger Hosp, Cook Cty Trauma Unit, Dept Surg, Chicago, IL USA. [Petrey, Laura B.] Baylor Univ, Med Ctr, Dept Surg, Dallas, TX 75246 USA. [Fabian, Timothy C.] Univ Tennessee, Ctr Hlth Sci, Dept Surg, Memphis, TN 38163 USA. RP Fox, N (reprint author), Cooper Univ Hosp, 1 Cooper Plaza, Camden, NJ 08103 USA. EM fox-nicole@cooperhealth.edu OI King, David/0000-0003-1028-1478; Brakenridge, Scott/0000-0002-7327-3718 NR 57 TC 17 Z9 17 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD JAN PY 2015 VL 78 IS 1 BP 136 EP 146 DI 10.1097/TA.0000000000000470 PG 11 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA AX3OB UT WOS:000346847500028 PM 25539215 ER PT J AU El-Hage, N Rodriguez, M Dever, SM Masvekar, RR Gewirtz, DA Shacka, JJ AF El-Hage, Nazira Rodriguez, Myosotys Dever, Seth M. Masvekar, Ruturaj R. Gewirtz, David A. Shacka, John J. TI HIV-1 and Morphine Regulation of Autophagy in Microglia: Limited Interactions in the Context of HIV-1 Infection and Opioid Abuse SO JOURNAL OF VIROLOGY LA English DT Article ID BECLIN 1-INDEPENDENT AUTOPHAGY; CELL-DEATH; T-CELLS; NEURONAL AUTOPHAGY; VIRUS TYPE-1; MECHANISM; GP120; TAT; MACROPHAGES; DEMENTIA AB Microglia are the predominant resident central nervous system (CNS) cell type productively infected by HIV-1, and play a key role in the progression of HIV-associated dementia (HAD). Moreover, neural dysfunction and progression to HAD are accelerated in opiate drug abusers. In the present study, we examined the role of the autophagy pathway in the neuropathogenesis of HIV-1 using primary human microglial cells and determined whether opiates converge at this point. Infection of microglia with the HIV-1(SF162) macrophage-tropic strain resulted in increased Beclin1 expression, accompanied by an increase of LC3 protein levels and accumulation of LC3 reporter RFP+ CFP+ (yellow) puncta, suggesting that HIV-1 infection triggers autophagosome formation without promoting protein degradation by the lysosome. Conversely, coexposure with HIV-1 and morphine significantly decreased virus-induced Beclin1 expression and autophagosome formation. Exploration of the possible mechanism(s) used by morphine to disrupt the autophagic process unveiled a significant increase in intracellular pH, which coincided with a reduction in the formation of acidic vesicular organelles and in autophagolysosome formation. Small interfering RNA targeting BECN1, a gene critical for autophagosome formation, significantly reduced viral replication and the virus-induced inflammatory responses. Conversely, morphine-enhanced viral replication and inflammatory responses were not affected by gene silencing with siBeclin1, suggesting that the interactive effect of morphine in HIV-1 pathogenesis is mediated through a Beclin1-independent mechanism. These novel findings may have important implications on the connections between autophagy and HIV-1 pathogenesis mediated by microglial cells in opioid-abusing individuals. IMPORTANCE About 50% of individuals infected with HIV-1 will develop some sort of neurocognitive impairment that cannot be prevented nor eradicated by antiretroviral therapy. The neuropathogenesis is mostly due to inflammatory responses by infected microglia, the resident immune cells of the brain. Cognitive disorders may also be associated with drugs of abuse. In fact, opioid drug users have an increased risk of developing neurocognitive disorders with increased progression to dementia. Although the mechanism(s) by which opioids exacerbate the neuropathogenesis of HIV-1 are not entirely known, it is well accepted that glia are critical to opiate responses. This study gives us new insight into possible autophagic mechanism(s) in microglia that control HIV-1 replication and virus-induced inflammation in the context of opioid abuse and should greatly improve our knowledge in the pathogenesis of HIV-1 resulting from substance abuse to provide a better understanding for the design of candidate antiviral therapies targeting drug-abusing individuals. C1 [El-Hage, Nazira; Dever, Seth M.; Gewirtz, David A.] Virginia Commonwealth Univ, Dept Pharmacol Toxicol, Richmond, VA 23284 USA. [Masvekar, Ruturaj R.] Virginia Commonwealth Univ, Dept Anat Neurobiol, Richmond, VA USA. [Rodriguez, Myosotys] Univ Cent Caribe, Dept Microbiol Immunol, Bayamon, PR USA. [Shacka, John J.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Shacka, John J.] Birmingham VA Med Ctr, Birmingham, AL USA. RP El-Hage, N (reprint author), Virginia Commonwealth Univ, Dept Pharmacol Toxicol, Med Coll Virginia Campus, Richmond, VA 23284 USA. EM nelhage@fiu.edu FU National Institutes of Health (NIH) [R01 DA036154, R03 DA026744, F32 DA033898]; NIH National Cancer Institute Cancer Center [P30 CA016059] FX This study was funded by National Institutes of Health (NIH) grants R01 DA036154 and R03 DA026744 (N.E.H.) and F32 DA033898 (S.M.D.). blow cytometry was supported, in part, by NIH National Cancer Institute Cancer Center support grant P30 CA016059. NR 74 TC 12 Z9 13 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD JAN PY 2015 VL 89 IS 2 BP 1024 EP 1035 DI 10.1128/JVI02022-14 PG 12 WC Virology SC Virology GA AX8SN UT WOS:000347178900012 PM 25355898 ER PT J AU Lorigan, P Ascierto, PA Dummer, R Eggermont, AM Flaherty, KT Garbe, C Gogas, H Hauschild, A Kefford, RF Kirkwood, JM Larkin, J Long, GV Maio, M McArthur, GA Ribas, A Robert, C Schadendorf, D Sondak, VK Wolchok, JD Hudson, AM AF Lorigan, Paul Ascierto, Paolo A. Dummer, Reinhard Eggermont, Alexander M. Flaherty, Keith T. Garbe, Claus Gogas, Helen Hauschild, Axel Kefford, Richard F. Kirkwood, John M. Larkin, James Long, Georgina V. Maio, Michele McArthur, Grant A. Ribas, Antoni Robert, Caroline Schadendorf, Dirk Sondak, Vernon K. Wolchok, Jedd D. Hudson, Andrew M. TI Expanded access programmes: patient interests versus clinical trial integrity SO LANCET ONCOLOGY LA English DT Editorial Material ID ADVANCED MELANOMA; TREMELIMUMAB; IPILIMUMAB; NIVOLUMAB; SURVIVAL C1 [Lorigan, Paul; Hudson, Andrew M.] Univ Manchester, Christie NHS Fdn Trust, Manchester, Lancs, England. [Ascierto, Paolo A.] Fdn Pascale, Ist Nazl Tumori, Naples, Italy. [Dummer, Reinhard] Univ Zurich, Zurich, Switzerland. [Flaherty, Keith T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Garbe, Claus] Univ Med Ctr Tubingen, Tubingen, Germany. [Gogas, Helen] Univ Athens, Dept Med, Athens, Greece. [Hauschild, Axel] Univ Hosp Schleswig Holstein, Kiel, Germany. [Kefford, Richard F.; Long, Georgina V.] Melanoma Inst Australia, Sydney, NSW, Australia. [Kefford, Richard F.; Long, Georgina V.] Univ Sydney, Sydney, NSW 2006, Australia. [Kefford, Richard F.] Macquarie Univ, Sydney, NSW 2109, Australia. [Maio, Michele] Univ Hosp Siena, Siena, Italy. [Kirkwood, John M.] Univ Pittsburgh, Melanoma Program, Inst Canc, Pittsburgh, PA USA. [Larkin, James] Royal Marsden Hosp NHS Fdn Trust, London, England. [McArthur, Grant A.] Peter MacCallum Canc Ctr, East Melbourne, Vic, Australia. [McArthur, Grant A.] Univ Melbourne, Parkville, Vic 3052, Australia. [Ribas, Antoni] Univ Calif Los Angeles, Los Angeles, CA USA. [Robert, Caroline] INSERM U981, Villejuif, France. [Sondak, Vernon K.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Wolchok, Jedd D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Lorigan, P (reprint author), Univ Manchester, Christie NHS Fdn Trust, Manchester, Lancs, England. EM paul.lorigan@christie.nhs.uk RI Lorigan, Paul/J-6898-2015; OI Lorigan, Paul/0000-0002-8875-2164; coral, sandra/0000-0002-1308-3082 FU NCI NIH HHS [P30 CA008748] NR 10 TC 2 Z9 2 U1 5 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD JAN PY 2015 VL 16 IS 1 BP 15 EP 17 PG 3 WC Oncology SC Oncology GA AX4OZ UT WOS:000346912800038 PM 25638540 ER PT J AU Garcia, JM Boccia, RV Graham, CD Yan, Y Duus, EM Allen, S Friend, J AF Garcia, Jose M. Boccia, Ralph V. Graham, Charles D. Yan, Ying Duus, Elizabeth Manning Allen, Suzan Friend, John TI Anamorelin for patients with cancer cachexia: an integrated analysis of two phase 2, randomised, placebo-controlled, double-blind trials SO LANCET ONCOLOGY LA English DT Article ID GROWTH-HORMONE SECRETAGOGUE; GHRELIN RECEPTOR AGONIST; HEALTHY-VOLUNTEERS; BODY-COMPOSITION; TUMOR-GROWTH; STRENGTH; ANOREXIA; MODEL; MASS; INTERLEUKIN-6 AB Background Cancer anorexia-cachexia syndrome is associated with increased morbidity and mortality. Anamorelin is an oral ghrelin-receptor agonist with appetite-enhancing and anabolic activity. We assessed the effects of anamorelin on body composition, strength, quality of life, biochemical markers, and safety in patients with cancer anorexia-cachexia. Methods Data were pooled, a priori, from two completed phase 2, multicentre, placebo-controlled, double-blind trials in patients with advanced or incurable cancer and weight loss of 5% or more. Patients were stratified by weight loss severity (5-15%, >15%) and randomly allocated (1: 1) with a computer-generated randomisation schedule to anamorelin hydrochloride 50 mg or placebo once-daily for 12 weeks. Primary outcome was lean body mass by dual-energy x-ray absorptiometry over the 12 week treatment period in eligible patients who had at least one dose of study drug and post-treatment efficacy assessment. We assessed safety in all patients who received at least one dose of study drug. The trials are registered with ClinicalTrials.gov, numbers NCT00219817 and NCT00267358. Findings Between June 29, 2005, and Oct 26, 2006, we enrolled 44 patients in the anamorelin group and 38 patients in the placebo group. 74 patients were eligible for the efficacy analyses. Over 12 weeks, lean body mass increased in 38 patients in the anamorelin group by a least-squares mean of 1.89 kg (95% CI 0.84 to 2.95) compared with a decrease of a least-squares mean of -0.20 kg (-1.23 to 0.83) for 36 patients in the placebo group (difference 2.09 kg [0.94-3.25]; p=0.0006). 42 (95%) of 44 patients treated with anamorelin and 33 (87%) of 38 patients treated with placebo had adverse events. The most common grade 3-4 adverse events (treatment-related or not) in the anamorelin group were fatigue, asthenia, atrial fibrillation, and dyspnoea (two [5%] each); in the placebo group, such events were pneumonia (three [8%]) and anaemia, thrombocytopenia, abdominal pain, anxiety, and dyspnoea (two [5%] each). Interpretation Anamorelin treatment for 12 weeks had a favourable clinical response profile in patients with cancer anorexia-cachexia syndrome. These findings support further investigation in this setting. C1 [Garcia, Jose M.] Michael E DeBakey VA Med Ctr, Ctr Translat Res Inflammatory Dis, Div Endocrinol Diabet & Metab, Houston, TX 77030 USA. [Boccia, Ralph V.] Georgetown Univ, Ctr Canc & Blood Disorders, Bethesda, MD USA. [Graham, Charles D.] Charleston Canc Ctr, Charleston, SC USA. [Yan, Ying; Duus, Elizabeth Manning; Allen, Suzan; Friend, John] Helsinn Therapeut, Bridgewater, NJ USA. RP Garcia, JM (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Div Endocrinol Diabet & Metab, 2002 Holcombe Blvd,Bldg 109,Room 210, Houston, TX 77030 USA. EM jgarcia1@bcm.edu FU Helsinn Therapeutics (US), Helsinn Healthcare SA FX Helsinn Therapeutics (US), Helsinn Healthcare SA. NR 36 TC 47 Z9 50 U1 3 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD JAN PY 2015 VL 16 IS 1 BP 108 EP 116 DI 10.1016/S1470-2045(14)71154-4 PG 9 WC Oncology SC Oncology GA AX4OZ UT WOS:000346912800050 PM 25524795 ER PT J AU Remenschneider, AK D'Amico, L Gray, ST Holbrook, EH Gliklich, RE Metson, R AF Remenschneider, Aaron K. D'Amico, Laura Gray, Stacey T. Holbrook, Eric H. Gliklich, Richard E. Metson, Ralph TI The EQ-5D: A New Tool for Studying Clinical Outcomes in Chronic Rhinosinusitis SO LARYNGOSCOPE LA English DT Article DE EQ-5D; quality of life; outcomes; assessment; chronic rhinosinusitis ID QUALITY-OF-LIFE; SINUS SURGERY; PROSPECTIVE COHORT; HEALTH SURVEY; UTILITY; IMPACT; SF-36; VALIDITY; INDEXES; SCORES AB Objectives/HypothesisTo describe the role and applicability of the EuroQol 5-Dimension, 5-Level (EQ-5D-5L) questionnaire for the assessment of general health-related quality of life in patients with chronic rhinosinusitis. Study DesignProspective cohort study. MethodsThe EQ-5D-5L was administered to 462 patients with refractory chronic rhinosinusitis before and 3 months after sinus surgery. Preoperative and postoperative scores across each of five health dimensions were analyzed and the results compared to those obtained from two widely used chronic rhinosinusitis outcomes instruments: the Chronic Sinusitis Survey (CSS) and SinoNasal Outcomes Test-22 (SNOT-22). ResultsThree hundred and fifty patients completed the five questions and visual analog scale (VAS) of the EQ-5D at baseline and at 3 months for a response rate of 75.8%. There were no incomplete questionnaires. The frequency of patients reporting problems in the EQ-5D domains of pain/discomfort, anxiety/depression, and usual activities decreased following sinus surgery (74.3% vs. 34.4%, 48.6% vs. 31.4%, and 30.6% vs. 19.4%, respectively; all P<0.001). The domains of mobility and self-care did not demonstrate statistically significant change. EQ-5D VAS (standard deviation) improved from 73.4 (16.9) before surgery to 82.0 (14.4) after surgery (P<0.001). Preoperative VAS correlated with SNOT-22 scores (Pearson coefficient of 0.50; P<0.01). Postoperative change in VAS and SNOT-22 scores demonstrated moderate correlation (Pearson coefficient of 0.36, P<0.01). ConclusionThe EQ-5D is a general health measure with sensitivity to clinical change in rhinosinusitis that support its use for monitoring patient outcomes. The limited response burden and ability to directly calculate health utility make it an attractive tool for rhinosinusitis outcomes research. Level of Evidence2c. Laryngoscope, 125:7-15, 2015 C1 [Remenschneider, Aaron K.; D'Amico, Laura; Gray, Stacey T.; Holbrook, Eric H.; Gliklich, Richard E.; Metson, Ralph] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Remenschneider, Aaron K.; Gray, Stacey T.; Holbrook, Eric H.; Gliklich, Richard E.; Metson, Ralph] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Remenschneider, AK (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Aaron_Remenschneider@meei.harvard.edu FU Committee on Quality of the Massachusetts Eye and Ear Infirmary, Boston, Massachusetts FX This work was supported by a funding grant from the Committee on Quality of the Massachusetts Eye and Ear Infirmary, Boston, Massachusetts. The authors have no other funding, financial relationships, or conflicts of interest to disclose. NR 37 TC 21 Z9 21 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD JAN PY 2015 VL 125 IS 1 BP 7 EP 15 DI 10.1002/lary.24715 PG 9 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA AX4NS UT WOS:000346909700005 PM 24729050 ER PT J AU Sethi, RKV Kozin, ED Remenschneider, AK Lee, DJ Gliklich, RE Shrime, MG Gray, ST AF Sethi, Rosh K. V. Kozin, Elliott D. Remenschneider, Aaron K. Lee, Daniel J. Gliklich, Richard E. Shrime, Mark G. Gray, Stacey T. TI Otolaryngology-Specific Emergency Room as a Model for Resident Training SO LARYNGOSCOPE LA English DT Article DE residency education; otolaryngology emergency room; otolaryngology procedures; Milestones project ID SIMULATION; IMPACT AB Objectives/HypothesisThere is a paucity of data on junior resident training in common otolaryngology procedures such as ear debridement, nasal and laryngeal endoscopy, epistaxis management, and peritonsillar abscess drainage. These common procedures represent a critical aspect of training and are necessary skills in general otolaryngology practice. We sought to determine how a dedicated otolaryngology emergency room (ER) staffed by junior residents and a supervising attending provides exposure to common otolaryngologic procedures. Study DesignRetrospective review. MethodsDiagnostic and procedural data for all patients examined in the Massachusetts Eye and Ear Infirmary ER between January 2011 and September 2013 were evaluated. ResultsA total of 12,234 patients were evaluated. A total of 5,673 patients (46.4%) underwent a procedure. Each second-year resident performed over 450 procedures, with the majority seen Monday through Friday (75%). The most common procedures in our study included diagnostic nasolaryngoscopy (52.0%), ear debridement (34.4%), and epistaxis control (7.0%) ConclusionsAn otolaryngology-specific ER provides junior residents with significant diagnostic and procedural volume in a concentrated period of time. This study demonstrates utility of a unique surgical education model and provides insight into new avenues of investigation for otolaryngology training. Level of Evidence4. Laryngoscope, 125:99-104, 2015 C1 [Sethi, Rosh K. V.; Lee, Daniel J.; Gliklich, Richard E.; Shrime, Mark G.; Gray, Stacey T.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Kozin, Elliott D.; Remenschneider, Aaron K.; Lee, Daniel J.; Gliklich, Richard E.; Shrime, Mark G.; Gray, Stacey T.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Shrime, Mark G.] Harvard Interfac Initiat Hlth Policy, Cambridge, MA USA. RP Gray, ST (reprint author), 243 Charles St, Boston, MA 02114 USA. EM stacey_gray@meei.harvard.edu RI Kozin, Elliott/J-1225-2014 OI Kozin, Elliott/0000-0002-0305-0682 FU NIDCD NIH HHS [T32 DC000020] NR 12 TC 3 Z9 3 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD JAN PY 2015 VL 125 IS 1 BP 99 EP 104 DI 10.1002/lary.24766 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA AX4NS UT WOS:000346909700025 PM 24912668 ER PT J AU Shin, JJ Caragacianu, D Randolph, GW AF Shin, Jennifer J. Caragacianu, Diana Randolph, Gregory W. TI Impact of Thyroid Nodule Size on Prevalence and Post-test Probability of Malignancy: A Systematic Review SO LARYNGOSCOPE LA English DT Article DE Thyroid nodule size; fine-needle aspiration biopsy; thyroid neoplasia; thyroid malignancy; systematic review ID FINE-NEEDLE-ASPIRATION; EVIDENCE-BASED MEDICINE; FALSE-NEGATIVE RATE; 4 CM; GREATER-THAN; INDEPENDENT PREDICTOR; DIAGNOSTIC-TESTS; BIOPSY; CARCINOMA; ACCURACY AB Objectives/HypothesisLarge thyroid nodules may be associated with higher risk of malignancy and less-accurate fine-needle aspiration (FNA) results, but there is currently no overarching consensus. We therefore tested two null hypotheses: 1) thyroid nodule size >3 to 4 cm is not associated with a higher baseline prevalence of malignancy (i.e., the associated pretest probability is the same, regardless of size), and 2) thyroid nodule size >3 to 4 cm is not associated with worse diagnostic accuracy (i.e., the associated sensitivity, false-negative rate, and post-test probability of malignancy is not affected by nodule diameter). Study DesignComputerized searches of PubMed, Embase, and The Cochrane Library through July 2013 were performed, supplemented with manual searches. MethodsA priori criteria were defined to determine inclusion and exclusion of studies. Searches and data extraction were performed by independent reviewers and focused on FNA histopathologic findings and their relationship to nodule size, study design, and potential confounders. ResultsCriterion-meeting studies (n=15) included a total of 13,180 participants. The preponderance of prospective comparative studies showed a statistically significantly higher prevalence of malignancy in large nodules. Although data are mixed, evidence from the best-reported studies suggests sensitivity, false-negative rates, and frequency of true negatives among benign FNA results are worse in large nodules. ConclusionsLarge nodules have a higher pretest probability of malignancy. Data from larger studies suggest reduced FNA diagnostic accuracy in nodules >3 to 4 cm in diameter. Surgery represents a reasonable clinical option for nodules >3 cm. Level of EvidenceNA Laryngoscope, 125:263-272, 2015 C1 [Shin, Jennifer J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Caragacianu, Diana] Massachusetts Eye & Ear Infirm, Div Thyroid & Parathyroid Surg, Boston, MA 02114 USA. [Randolph, Gregory W.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. Doctors Borders, Dept Monitoring & Evaluat, Johannesburg, South Africa. RP Shin, JJ (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM jennifer_shin@meei.harvard.edu NR 39 TC 8 Z9 8 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD JAN PY 2015 VL 125 IS 1 BP 263 EP 272 DI 10.1002/lary.24784 PG 10 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA AX4NS UT WOS:000346909700051 PM 24965892 ER PT J AU Graedel, NN Polimeni, JR Guerin, B Gagoski, B Wald, LL AF Graedel, Nadine N. Polimeni, Jonathan R. Guerin, Bastien Gagoski, Borjan Wald, Lawrence L. TI An Anatomically Realistic Temperature Phantom for Radiofrequency Heating Measurements SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE phantom; thermometry; MR safety; local SAR; parallel transmit; temperature estimation ID HUMAN HEAD; IN-VIVO; MR THERMOMETRY; ANTHROPOMORPHIC PHANTOMS; PARALLEL TRANSMISSION; DIELECTRIC-PROPERTIES; ABSORPTION RATE; SAR; RESONANCE; MODEL AB PurposeAn anthropomorphic phantom with realistic electrical properties allows for a more accurate reproduction of tissue current patterns during excitation. A temperature map can then probe the worst-case heating expected in the unperfused case. We describe an anatomically realistic human head phantom that allows rapid three-dimensional (3D) temperature mapping at 7T. MethodsThe phantom was based on hand-labeled anatomical imaging data and consists of four compartments matching the corresponding human tissues in geometry and electrical properties. The increases in temperature resulting from radiofrequency excitation were measured with MR thermometry using a temperature-sensitive contrast agent (TmDOTMA(-)) validated by direct fiber optic temperature measurements. ResultsAcquisition of 3D temperature maps of the full phantom with a temperature accuracy better than 0.1 degrees C was achieved with an isotropic resolution of 5 mm and acquisition times of 2-4 minutes. ConclusionOur results demonstrate the feasibility of constructing anatomically realistic phantoms with complex geometries incorporating the ability to measure accurate temperature maps in the phantom. The anthropomorphic temperature phantom is expected to provide a useful tool for the evaluation of the heating effects of both conventional and parallel transmit pulses and help validate electromagnetic and temperature simulations. Magn Reson Med 73:442-450, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [Graedel, Nadine N.; Polimeni, Jonathan R.; Guerin, Bastien; Wald, Lawrence L.] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Polimeni, Jonathan R.; Wald, Lawrence L.] Harvard Univ, Sch Med, Boston, MA USA. [Gagoski, Borjan] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Wald, Lawrence L.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. RP Wald, LL (reprint author), Bldg 75,Room 2-109, Charlestown, MA 02129 USA. EM wald@nmr.mgh.harvard.edu RI Polimeni, Jonathan/P-1395-2014; Wald, Lawrence/D-4151-2009 OI Polimeni, Jonathan/0000-0002-1348-1179; FU National Center for Research Resources [P41-RR14075]; National Institute of Biomedical Imaging and Bioengineering [R01-EB006847, K01-EB011498]; EPFL-WISH Foundation FX Grant sponsor: National Center for Research Resources; Grant number: P41-RR14075; Grant sponsor: National Institute of Biomedical Imaging and Bioengineering; Grant numbers: R01-EB006847; K01-EB011498; Grant sponsor: The EPFL-WISH Foundation. NR 44 TC 7 Z9 7 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD JAN PY 2015 VL 73 IS 1 BP 442 EP 450 DI 10.1002/mrm.25123 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AX4NJ UT WOS:000346908800042 PM 24549755 ER PT J AU Samuel, CA Zaslavsky, AM Landrum, MB Lorenz, K Keating, NL AF Samuel, Cleo A. Zaslavsky, Alan M. Landrum, Mary Beth Lorenz, Karl Keating, Nancy L. TI Developing and Evaluating Composite Measures of Cancer Care Quality SO MEDICAL CARE LA English DT Article DE cancer care; quality measurement; composites ID PROSTATE-CANCER; OF-CARE; MULTIPLE COMPARISONS; AMBULATORY-CARE; PERFORMANCE; RADIOTHERAPY; INDICATORS; CASTRATION; CARCINOMA; VETERANS AB Background:Composite measures are useful for distilling quality data into summary scores; yet, there has been limited use of composite measures for cancer care.Objective:Compare multiple approaches for generating cancer care composite measures and evaluate how well composite measures summarize dimensions of cancer care and predict survival.Study Design:We computed hospital-level rates for 13 colorectal, lung, and prostate cancer process measures in 59 Veterans Affairs hospitals. We computed 4 empirical-factor (based on an exploratory factor analysis), 3 cancer-specific (colorectal, lung, prostate care), and 3 care modality-specific (diagnosis/evaluation, surgical, nonsurgical treatments) composite measures. We assessed correlations among all composite measures and estimated all-cause survival for colon, rectal, non-small cell lung, and small cell lung cancers as a function of composite scores, adjusting for patient characteristics.Results:Four factors emerged from the factor analysis: nonsurgical treatment, surgical treatment, colorectal early diagnosis, and prostate treatment. We observed strong correlations (r) among composite measures comprised of similar process measures (r=0.58-1.00, P<0.0001), but not among composite measures reflecting different care dimensions. Composite measures were rarely associated with survival.Conclusions:The empirical-factor domains grouped measures variously by cancer type and care modality. The evidence did not support any single approach for generating cancer care composite measures. Weak associations across different care domains suggest that low-quality and high-quality cancer care delivery may coexist within Veterans Affairs hospitals. C1 [Samuel, Cleo A.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Policy & Management, Chapel Hill, NC USA. [Zaslavsky, Alan M.; Landrum, Mary Beth; Keating, Nancy L.] Harvard Univ, Dept Hlth Care Policy, Sch Med, Boston, MA 02115 USA. [Lorenz, Karl] Vet Adm Greater Los Angeles Healthcare Syst, Div Gen Internal Med, Los Angeles, CA USA. [Lorenz, Karl] Vet Adm Greater Los Angeles Healthcare Syst, Div Palliat Care, Los Angeles, CA USA. [Lorenz, Karl] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. RP Keating, NL (reprint author), Harvard Univ, Dept Hlth Care Policy, Sch Med, 180 Longwood Ave, Boston, MA 02115 USA. EM keating@hcp.med.harvard.edu FU Department of Veterans Affairs through the Office of Policy and Planning as part of an evaluation of oncology care; Ruth L. Kirschstein National Research Service Award; Harvard University Graduate Prize Fellowship FX Supported by the Department of Veterans Affairs through the Office of Policy and Planning as part of an evaluation of oncology care. C.A.S.'s effort was supported by the Ruth L. Kirschstein National Research Service Award and the Harvard University Graduate Prize Fellowship. NR 40 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD JAN PY 2015 VL 53 IS 1 BP 54 EP 64 DI 10.1097/MLR.0000000000000257 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AX0OE UT WOS:000346650700010 PM 25373407 ER PT J AU Aldridge, MD Canavan, M Cherlin, E Bradley, EH AF Aldridge, Melissa D. Canavan, Maureen Cherlin, Emily Bradley, Elizabeth H. TI Has Hospice Use Changed? 2000-2010 Utilization Patterns SO MEDICAL CARE LA English DT Article DE hospice; Medicare hospice benefit; health services research ID ENROLLMENT; CARE; CAREGIVERS; MEDICARE; DEPRESSION; LENGTH AB Background:Hospice use has increased substantially during the past decade by an increasingly diverse patient population; however, little is known about patterns of hospice use and how these patterns have changed during the past decade.Objective:To characterize Medicare hospice users in 2000 and 2010 and estimate the prevalence of (1) very short (1 wk) hospice enrollment; (2) very long (>6 mo) hospice enrollment; and (3) hospice disenrollment and how these utilization patterns have varied over time and by patient and hospice characteristics.Research Design:Cross-sectional analysis of Medicare hospice claims data from 2000 and 2010.Subjects:All US Medicare Hospice Benefit enrollees in 2000 (N=529,573) and 2010 (N=1,150,194).Results:As of 2010, more than half (53.4%) of all Medicare decedents who used hospice had either very short (1 wk, 32.4%) or very long (>6 mo, 13.9%) hospice enrollment or disenrolled from hospice before death (10.6%). This represents an increase of 4.9 percentage points from 2000. In multivariable analysis, patients with noncancer diagnoses, the fastest growing group of hospice users, were approximately twice as likely as those with cancer to have very short or long enrollment periods and to disenroll from hospice.Conclusion:The substantial proportion of hospice users with very short or long enrollment, or enrollments that end before death, underscores the potential for interventions to improve the timing and appropriateness of hospice referral so that the full benefits of hospice are received by patients and families. C1 [Aldridge, Melissa D.] Icahn Sch Med Mt Sinai, Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Aldridge, Melissa D.] James J Peters VA Med Ctr, Bronx, NY USA. [Canavan, Maureen; Cherlin, Emily; Bradley, Elizabeth H.] Yale Univ, Sch Publ Hlth, Dept Hlth Policy & Management, New Haven, CT USA. RP Aldridge, MD (reprint author), Icahn Sch Med Mt Sinai, Dept Geriatr & Palliat Med, One Gustave L Levy Pl,POB 1070, New York, NY 10029 USA. EM melissa.aldridge@mssm.edu FU National Institute of Nursing Research [5R01NR013499]; John D. Thompson Foundation FX Supported by the National Institute of Nursing Research 5R01NR013499 (M.D.A.); and the John D. Thompson Foundation (E.H.B.). NR 27 TC 14 Z9 14 U1 7 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD JAN PY 2015 VL 53 IS 1 BP 95 EP 101 DI 10.1097/MLR.0000000000000256 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AX0OE UT WOS:000346650700015 PM 25373406 ER PT J AU Petitjean, C Zuluaga, MA Bai, WJ Dacher, JN Grosgeorge, D Caudron, J Ruan, S Ben Ayed, I Cardoso, MJ Chen, HC Jimenez-Carretero, D Ledesma-Carbayo, MJ Davatzikos, C Doshi, J Erus, G Maier, OMO Nambakhsh, CMS Ou, YM Ourselin, S Peng, CW Peters, NS Peters, TM Rajchi, M Rueckert, D Santos, A Shi, WZ Wang, CW Wang, HY Yuan, J AF Petitjean, Caroline Zuluaga, Maria A. Bai, Wenjia Dacher, Jean-Nicolas Grosgeorge, Damien Caudron, Jerome Ruan, Su Ben Ayed, Ismail Cardoso, M. Jorge Chen, Hsiang-Chou Jimenez-Carretero, Daniel Ledesma-Carbayo, Maria J. Davatzikos, Christos Doshi, Jimit Erus, Guray Maier, Oskar M. O. Nambakhsh, Cyrus M. S. Ou, Yangming Ourselin, Sebastien Peng, Chun-Wei Peters, Nicholas S. Peters, Terry M. Rajchi, Martin Rueckert, Daniel Santos, Andres Shi, Wenzhe Wang, Ching-Wei Wang, Haiyan Yuan, Jing TI Right ventricle segmentation from cardiac MRI: A collation study SO MEDICAL IMAGE ANALYSIS LA English DT Article DE Cardiac MRI; Right ventricle segmentation; Segmentation method evaluation; Segmentation challenge; Collation study ID ACTIVE SHAPE MODELS; WHOLE HEART SEGMENTATION; CINE MRI; AUTOMATIC SEGMENTATION; SHORT-AXIS; IMAGES; REGISTRATION; QUANTIFICATION; VARIABILITY; PERFORMANCE AB Magnetic Resonance Imaging (MRI), a reference examination for cardiac morphology and function in humans, allows to image the cardiac right ventricle (RV) with high spatial resolution. The segmentation of the RV is a difficult task due to the variable shape of the RV and its ill-defined borders in these images. The aim of this paper is to evaluate several RV segmentation algorithms on common data. More precisely, we report here the results of the Right Ventricle Segmentation Challenge (RVSC), concretized during the MICCAI'12 Conference with an on-site competition. Seven automated and semi-automated methods have been considered, along them three atlas-based methods, two prior based methods, and two prior-free, image-driven methods that make use of cardiac motion. The obtained contours were compared against a manual tracing by an expert cardiac radiologist, taken as a reference, using Dice metric and Hausdorff distance. We herein describe the cardiac data composed of 48 patients, the evaluation protocol and the results. Best results show that an average 80% Dice accuracy and a 1 cm Hausdorff distance can be expected from semi-automated algorithms for this challenging task on the datasets, and that an automated algorithm can reach similar performance, at the expense of a high computational burden. Data are now publicly available and the website remains open for new submissions (http://www.litislab.eu/rvsc/). (C) 2014 Elsevier B.V. All rights reserved. C1 [Petitjean, Caroline; Grosgeorge, Damien; Ruan, Su] Univ Rouen, LITIS EA 4108, F-76801 St Etienne, France. [Zuluaga, Maria A.; Cardoso, M. Jorge; Ourselin, Sebastien] UCL, Ctr Med Image Comp, London, England. [Dacher, Jean-Nicolas; Caudron, Jerome] Univ Rouen, INSERM U1096, F-76031 Rouen, France. [Bai, Wenjia; Rueckert, Daniel; Shi, Wenzhe; Wang, Haiyan] Univ London Imperial Coll Sci Technol & Med, Dept Comp, Biomed Image Anal Grp, London SW7 2AZ, England. [Peters, Nicholas S.] Univ London Imperial Coll Sci Technol & Med, St Marys Hosp, Natl Heart & Lung Inst, London SW7 2AZ, England. [Jimenez-Carretero, Daniel; Ledesma-Carbayo, Maria J.; Maier, Oskar M. O.; Santos, Andres] Univ Politecn Madrid, E-28040 Madrid, Spain. [Jimenez-Carretero, Daniel; Ledesma-Carbayo, Maria J.; Maier, Oskar M. O.; Santos, Andres] CIBERBBN, Madrid, Spain. [Chen, Hsiang-Chou; Peng, Chun-Wei; Wang, Ching-Wei] Natl Taiwan Univ Sci & Technol, Grad Inst Biomed Engn, Taipei, Taiwan. [Ben Ayed, Ismail] GE Healthcare, London, ON, Canada. [Nambakhsh, Cyrus M. S.; Peters, Terry M.; Rajchi, Martin; Yuan, Jing] Univ Western Ontario, Robarts Res Inst, London, ON, Canada. [Davatzikos, Christos; Doshi, Jimit; Erus, Guray; Ou, Yangming] Univ Penn, Dept Radiol, Sect Biomed Image Anal, Philadelphia, PA 19104 USA. [Ou, Yangming] Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Biomed Imaging Ctr, Charlestown, MA USA. RP Petitjean, C (reprint author), Univ Rouen, LITIS EA 4108, F-76801 St Etienne, France. EM Caroline.Petitjean@univ-rouen.fr RI Santos, Andres/C-4012-2009; Peters, Terry/K-6853-2013; Yuan, Jing/E-8080-2015; Ledesma-Carbayo, Maria /D-5529-2009; Bai, Wenjia/B-3377-2017 OI Santos, Andres/0000-0001-7423-9135; Peters, Terry/0000-0003-1440-7488; Yuan, Jing/0000-0002-4312-7023; Ledesma-Carbayo, Maria /0000-0001-6846-3923; Bai, Wenjia/0000-0003-2943-7698 FU BHF [RG/10/11/28457]; NIHR Biomedical Research Centre; EPSRC [EP/H046410/1, EP/J020990/1, EP/K005278]; MRC [MR/J01107X/1]; EU-FP7 project VPH-DARE@IT [FP7-ICT-2011-9-601055]; NIHR Biomedical Research Unit (Dementia) at UCL; National Institute for Health Research University College London Hospitals Biomedical Research Centre (NIHR BRC UCLH/UCL High Impact Initiative); National Science Council of Taiwan [NSC101-2628-E-011-006-MY3]; Spanish Ministry of Science and Innovation through CDTI CENIT (AMIT); Comunidad de Madrid [ARTEMIS S2009/DPI-1802]; European Funds (FEDER); [TEC2010-21619-004-03]; [TEC2011-28972-C02-02]; [FP7-PEOPLE-2010-IRSES-269300 TAHITI] FX The anonymous reviewers are acknowledged for their detailed, qualified and constructive reviews. W. Bai is supported by the BHF Grant RG/10/11/28457 and NIHR Biomedical Research Centre funding. M.A. Zuluaga and M.J. Cardoso are funded by an EPSRC Grant (EP/H046410/1). S. Ourselin receives funding from the EPSRC (EP/H046410/1, EP/J020990/1, EP/K005278), the MRC (MR/J01107X/1), the EU-FP7 project VPH-DARE@IT (FP7-ICT-2011-9-601055), the NIHR Biomedical Research Unit (Dementia) at UCL and the National Institute for Health Research University College London Hospitals Biomedical Research Centre (NIHR BRC UCLH/UCL High Impact Initiative). H.-C. Chen and C.-W. Peng are supported by the National Science Council of Taiwan with the project number NSC101-2628-E-011-006-MY3. O.M.O. Maier, D. Jimenez-Carretero, A. Santos and M.J. Ledesma-Carbayo's work is partially funded by Spanish Ministry of Science and Innovation through CDTI CENIT (AMIT) and projects TEC2010-21619-004-03 and TEC2011-28972-C02-02; Comunidad de Madrid (ARTEMIS S2009/DPI-1802), and the European Funds (FEDER) and FP7-PEOPLE-2010-IRSES-269300 TAHITI. NR 53 TC 17 Z9 18 U1 5 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1361-8415 EI 1361-8423 J9 MED IMAGE ANAL JI Med. Image Anal. PD JAN PY 2015 VL 19 IS 1 BP 187 EP 202 DI 10.1016/j.media.2014.10.004 PG 16 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA AY0DO UT WOS:000347268200015 PM 25461337 ER PT J AU Friedman, JM Mantzoros, CS AF Friedman, Jeffrey M. Mantzoros, Christos S. TI 20 years of leptin: From the discovery of the leptin gene to leptin in our therapeutic armamentarium SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Editorial Material ID HYPOTHALAMIC AMENORRHEA; OBESE GENE; RECOMBINANT LEPTIN; ANOREXIA-NERVOSA; IN-VITRO; MICE; WEIGHT; MUTATION; RECEPTOR; PROTEIN C1 [Friedman, Jeffrey M.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Endocrinol Sect, VA Boston Healthcare Syst, Boston, MA USA. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Div Endocrinol, Beth Israel Deaconess Med Ctr, Boston, MA USA. RP Friedman, JM (reprint author), Rockefeller Univ, 1230 York Ave, New York, NY 10065 USA. NR 41 TC 20 Z9 20 U1 3 U2 20 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD JAN PY 2015 VL 64 IS 1 BP 1 EP 4 DI 10.1016/j.metabol.2014.10.023 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX1GC UT WOS:000346694900001 PM 25497341 ER PT J AU Tsoukas, MA Farr, OM Mantzoros, CS AF Tsoukas, Michael A. Farr, Olivia M. Mantzoros, Christos S. TI Leptin in congenital and HIV-associated lipodystrophy SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article DE Leptin; Congenital lipodystrophy; HIV-associated lipodystrophy; Metabolism ID ACTIVE ANTIRETROVIRAL THERAPY; PLACEBO-CONTROLLED TRIAL; HUMAN GROWTH-HORMONE; INHIBITOR-ASSOCIATED LIPODYSTROPHY; REVERSES INSULIN-RESISTANCE; RANDOMIZED CONTROLLED-TRIAL; ABDOMINAL FAT ACCUMULATION; RECOMBINANT HUMAN LEPTIN; MULTICENTER AIDS COHORT; LONG-TERM EFFICACY AB Leptin is a hormone secreted by adipocytes that regulates energy metabolism via peripheral action on glucose synthesis and utilization as well as through central regulation of food intake. Patients with decreased amounts of fat in their adipose tissue (lipoatrophy) will have low leptin levels, and hypoleptinemic states have been associated with a variety of metabolic dysfunctions. Pronounced complications of insulin resistance, dyslipidemia and fatty liver are observed in patients suffering from congenital or acquired generalized lipodystrophy while somewhat less pronounced abnormalities are associated with human immunodeficiency virus (HIV) and the use of highly active antiretroviral therapy, the so-called HIV-associated lipodystrophy. Previous uncontrolled open-label studies have demonstrated that physiological doses of leptin repletion have corrected many of the metabolic derangements observed in subjects with rare fat maldistribution syndromes such as generalized lipodystrophy. In the much more commonly encountered HIV-associated lipodystrophy, leptin replacement has been shown to decrease central fat mass and to improve insulin sensitivity, dyslipidemia, and glucose levels. The United States Food and Drug Administration has recently granted approval for recombinant leptin therapy for congenital and acquired generalized lipodystrophy, however large, well-designed, placebo-controlled studies are needed to assess long-term efficacy, safety and adverse effects of leptin replacement. In this review, we present the role of leptin in the metabolic complications of congenital and acquired lipodystrophy and discuss current and emerging clinical therapeutic uses of leptin in humans with lipodystrophy. (C) 2015 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Sect Endocrinol,Boston VA Healthcare Syst, Boston, MA 02215 USA. [Tsoukas, Michael A.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. RP Tsoukas, MA (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. EM mtsouka1@bidmc.harvard.edu OI Farr, Olivia/0000-0002-5182-3432 NR 144 TC 12 Z9 12 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 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD JAN PY 2015 VL 64 IS 1 BP 47 EP 59 DI 10.1016/j.metabol.2014.07.017 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX1GC UT WOS:000346694900006 PM 25267014 ER PT J AU Upadhyay, J Farr, OM Mantzoros, CS AF Upadhyay, Jagriti Farr, Olivia M. Mantzoros, Christos S. TI The role of leptin in regulating bone metabolism SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article DE Leptin; Bone; Osteoporosis ID GROWTH-FACTOR-I; OSTEOBLAST-ENRICHED CULTURES; SYMPATHETIC-NERVOUS-SYSTEM; FETAL-RAT BONE; ANOREXIA-NERVOSA; HYPOTHALAMIC AMENORRHEA; MINERAL DENSITY; PARATHYROID-HORMONE; MORBID-OBESITY; FAT MASS AB Leptin was initially best known for its role in energy homeostasis and regulation of energy expenditure. In the past few years we have realized that leptin also plays a major role in neuroendocrine regulation and bone metabolism. Here, we review the literature the indirect and direct pathways through which leptin acts to influence bone metabolism and discuss bone abnormalities related to leptin deficiency in both animal and human studies. The clinical utility of leptin in leptin deficient individuals and its potential to improve metabolic bone disease are also discussed. We are beginning to understand the critical role leptin plays in bone metabolism; future randomized studies are needed to fully assess the potential and risk-benefit of leptin's use in metabolic bone disease particularly in leptin deficient individuals. (C) 2015 Published by Elsevier Inc. C1 [Upadhyay, Jagriti; Farr, Olivia M.; Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Div Endocrinol, Boston, MA 02215 USA. RP Upadhyay, J (reprint author), VA Boston Healthcare Syst, Div Endocrinol 9-B,150S Huntington Ave, Boston, MA 02130 USA. EM upadhya@bidmc.harvard.edu OI Farr, Olivia/0000-0002-5182-3432 FU NIH [5T32HD052961] FX NIH 5T32HD052961. NR 103 TC 10 Z9 10 U1 0 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD JAN PY 2015 VL 64 IS 1 BP 105 EP 113 DI 10.1016/j.metabol.2014.10.021 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX1GC UT WOS:000346694900010 PM 25497343 ER PT J AU Farr, OM Tsoukas, MA Mantzoros, CS AF Farr, Olivia M. Tsoukas, Michael A. Mantzoros, Christos S. TI Leptin and the brain: Influences on brain development, cognitive functioning and psychiatric disorders SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article DE CNS; Leptin; fMRI; Schizophrenia; Depression ID HIPPOCAMPAL SYNAPTIC PLASTICITY; CENTRAL-NERVOUS-SYSTEM; REGULATES FOOD-INTAKE; DIET-INDUCED OBESITY; HYPOTHALAMIC ARCUATE NUCLEUS; ACTIVATED PROTEIN-KINASE; RECEPTOR MESSENGER-RNA; LONG-TERM POTENTIATION; INDUCED DIABETIC-RATS; BODY-WEIGHT GAIN AB Receptors of leptin, the prototypical adipokine, are expressed throughout the cortex and several other areas of the brain. Although typically studied for its role in energy intake and expenditure, leptin plays a critical role in many other neurocognitive processes and interacts with various other hormones and neurotransmitters to perform these functions. Here, we review the literature on how leptin influences brain development, neural degradation, Alzheimer's disease, psychiatric disorders, and more complicated cognitive functioning and feeding behaviors. We also discuss modulators of leptin and the leptin receptor as they relate to normal cognitive functioning and may mediate some of the actions of leptin in the brain. Although we are beginning to better understand the critical role leptin plays in normal cognitive functioning, there is much to be discovered. (C) 2015 Elsevier Inc. All rights reserved. C1 [Farr, Olivia M.; Tsoukas, Michael A.; Mantzoros, Christos S.] Harvard Univ, Sch Med, Div Endocrinol, Boston VA Healthcare Syst, Boston, MA 02215 USA. RP Farr, OM (reprint author), VA Boston Healthcare Syst, Div Endocrinol, Div Endocrinol 9-B,150 S,Huntington Ave, Boston, MA 02130 USA. EM Olivia.Farr@va.gov OI Farr, Olivia/0000-0002-5182-3432 NR 249 TC 20 Z9 20 U1 1 U2 18 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD JAN PY 2015 VL 64 IS 1 BP 114 EP 130 DI 10.1016/j.metabol.2014.07.004 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX1GC UT WOS:000346694900011 PM 25092133 ER PT J AU Lauwers, GY Fasano, A Brown, IS AF Lauwers, Gregory Y. Fasano, Alessio Brown, Ian S. TI Duodenal lymphocytosis with no or minimal enteropathy: much ado about nothing? SO MODERN PATHOLOGY LA English DT Article ID GLUTEN-SENSITIVE ENTEROPATHY; COMMON VARIABLE IMMUNODEFICIENCY; CELIAC-DISEASE; INTRAEPITHELIAL LYMPHOCYTES; VILLOUS ARCHITECTURE; TROPICAL-SPRUE; JEJUNAL MUCOSA; FOLLOW-UP; BIOPSY; DIAGNOSIS AB Duodenal lymphocytosis is a nonspecific finding that is being detected with heightened frequency. Although increased intraepithelial lymphocytosis with normal villous architecture classically corresponds to grade 1 of the Marsh classification, many other conditions have been reported to be associated with this histologic pattern. In this article, we offer a broad review of the associations of isolated increased intraepithelial lymphocytosis with celiac and nonceliac gluten sensitivity, as well as of the broadening nonceliac etiologies. C1 [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Boston, MA 02114 USA. [Fasano, Alessio] MassGeneral Hosp Children, Div Pediat Gastroenterol & Nutr, Boston, MA USA. [Brown, Ian S.] Envoi Pathol, Brisbane, Qld, Australia. RP Lauwers, GY (reprint author), Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, 55 Fruit St,WRN 219, Boston, MA 02114 USA. EM GLAUWERS@PARTNERS.ORG RI Brown, Ian/R-7763-2016 OI Brown, Ian/0000-0001-6329-2547 NR 54 TC 2 Z9 2 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2015 VL 28 SU 1 BP S22 EP S29 DI 10.1038/modpathol.2014.135 PG 8 WC Pathology SC Pathology GA AY1YD UT WOS:000347384700003 PM 25560597 ER PT J AU Misdraji, J AF Misdraji, Joseph TI Mucinous epithelial neoplasms of the appendix and pseudomyxoma peritonei SO MODERN PATHOLOGY LA English DT Article ID LONG-TERM SURVIVAL; SIGNET-RING CELLS; VERMIFORM APPENDIX; CLINICOPATHOLOGICAL ANALYSIS; PRIMARY ADENOCARCINOMA; INTRAPERITONEAL CHEMOTHERAPY; CYTOREDUCTIVE SURGERY; VILLOUS ADENOMA; INTESTINAL METAPLASIA; RIGHT HEMICOLECTOMY AB The classification of appendiceal mucinous neoplasms has been controversial, largely focused on a particular subset of low-grade mucinous tumors that, despite their innocuous appearance, can disseminate to the peritoneal cavity as pseudomyxoma peritonei (PMP). Recent WHO classification of these tumors as low-grade appendiceal mucinous neoplasms acknowledges their unique morphologic appearance and biologic behavior. Still, debate about the use of this term and its parameters continues to impede the adoption of consensus classification for appendiceal mucinous neoplasms. The classification of PMP has also been the subject of debate, with international authorities advocating for the use of malignant terminology to describe all grades of PMP, even though some authorities consider low-grade PMP to be dissemination of adenomatous epithelium in the peritoneum. Recent data also emphasize the importance of histologic grade of the peritoneal tumors in defining prognosis of these patients. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Misdraji, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, 55 Fruit St,Warren 831, Boston, MA 02114 USA. EM jmisdraji@partners.org NR 89 TC 13 Z9 14 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2015 VL 28 SU 1 BP S67 EP S79 DI 10.1038/modpathol.2014.129 PG 13 WC Pathology SC Pathology GA AY1YD UT WOS:000347384700006 PM 25560600 ER PT J AU Bao, LD Si, Q Jia, LZ Ren, XH Ma, RL Wang, Y AF Bao, Lidao Si, Qin Jia, Lizhou Ren, Xianhua Ma, Ruilian Wang, Yi TI Detection of human papillomavirus and expression of osteopontin in cervical cancer specimens SO MOLECULAR MEDICINE REPORTS LA English DT Article DE cervical cancer; human papillomavirus typing; osteopontin; expression ID HPV VACCINATION; GENE POLYMORPHISMS; INFECTION; WOMEN; RISK; SUSCEPTIBILITY; PREVALENCE; CYTOLOGY; TRIAGE; DNA AB To understand human papillomavirus (HPV) and expression of osteopontin (OPN) in cervical diseased tissues, HPV infection was detected in paraffin-embedded specimens of cervical lesions from 90 patients with cervical cancer. Three polymerase chain reaction (PCR) techniques were used to determine the detectable rate of HPV infection. Expression of HPV OPN protein was detected using immunohistochemical methods. When a pairwise comparison was made among the three PCR methods, (2) analysis indicated P>0.05 for detection through the methods of MY09/11 and GP5(+)/6(+), and P>0.05 through the methods of MY09/11 and Nested-PCR. This indicated that there was no statistically significant difference in the HPV infection detection sensitivity of these methods. However, (2) comparison of the methods of GP5(+)/6(+) and Nested-PCR indicated P<0.05, which demonstrated that there was a statistically significant difference. The rate of positive HPV DNA measured with Nested-PCR was significantly higher than that measured using the GP5(+)/6(+) PCR method. The HPV OPN protein is expressed in cervical cancer, and the HPV OPN polypeptide antibody has broad spectrum reaction capacity and significant multivalence for HPV infection. Immunohistochemical detection was performed on tissue specimens using the purified rabbit HPV OPN polypeptide antibody. Sixty-one cases exhibited a positive result and 29 a negative result. The total rate of positive detection was 67.78%. HPV OPN may therefore serve as a candidate target for tumor treatment, including targeted therapies and vaccine development. C1 [Bao, Lidao; Ren, Xianhua; Ma, Ruilian; Wang, Yi] Inner Mongolia Med Univ, Dept Pharm, Affiliated Hosp, Hohhot 010059, Inner Mongolia, Peoples R China. [Si, Qin; Jia, Lizhou] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02120 USA. RP Wang, Y (reprint author), Inner Mongolia Med Univ, Dept Pharm, Affiliated Hosp, 1 Tongdaobei St, Hohhot 010059, Inner Mongolia, Peoples R China. EM wang_yi237@163.com NR 37 TC 0 Z9 0 U1 0 U2 7 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1791-2997 EI 1791-3004 J9 MOL MED REP JI Mol. Med. Rep. PD JAN PY 2015 VL 11 IS 1 BP 447 EP 453 DI 10.3892/mmr.2014.2647 PG 7 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA AX0OH UT WOS:000346651100063 PM 25323451 ER PT J AU Muona, M Berkovic, SF Dibbens, LM Oliver, KL Maljevic, S Bayly, MA Joensuu, T Canafoglia, L Franceschetti, S Michelucci, R Markkinen, S Heron, SE Hildebrand, MS Andermann, E Andermann, F Gambardella, A Tinuper, P Licchetta, L Scheffer, IE Criscuolo, C Filla, A Ferlazzo, E Ahmad, J Ahmad, A Baykan, B Said, E Topcu, M Riguzzi, P King, MD Ozkara, C Andrade, DM Engelsen, BA Crespel, A Lindenau, M Lohmann, E Saletti, V Massano, J Privitera, M Espay, AJ Kauffmann, B Duchowny, M Moller, RS Straussberg, R Afawi, Z Ben-Zeev, B Samocha, KE Daly, MJ Petrou, S Lerche, H Palotie, A Lehesjoki, AE AF Muona, Mikko Berkovic, Samuel F. Dibbens, Leanne M. Oliver, Karen L. Maljevic, Snezana Bayly, Marta A. Joensuu, Tarja Canafoglia, Laura Franceschetti, Silvana Michelucci, Roberto Markkinen, Salla Heron, Sarah E. Hildebrand, Michael S. Andermann, Eva Andermann, Frederick Gambardella, Antonio Tinuper, Paolo Licchetta, Laura Scheffer, Ingrid E. Criscuolo, Chiara Filla, Alessandro Ferlazzo, Edoardo Ahmad, Jamil Ahmad, Adeel Baykan, Betul Said, Edith Topcu, Meral Riguzzi, Patrizia King, Mary D. Ozkara, Cigdem Andrade, Danielle M. Engelsen, Bernt A. Crespel, Arielle Lindenau, Matthias Lohmann, Ebba Saletti, Veronica Massano, Joao Privitera, Michael Espay, Alberto J. Kauffmann, Birgit Duchowny, Michael Moller, Rikke S. Straussberg, Rachel Afawi, Zaid Ben-Zeev, Bruria Samocha, Kaitlin E. Daly, Mark J. Petrou, Steven Lerche, Holger Palotie, Aarno Lehesjoki, Anna-Elina TI A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy SO NATURE GENETICS LA English DT Article ID SHAKER K+ CHANNEL; DNA-SEQUENCING DATA; ATAXIA TYPE 13; POTASSIUM CHANNEL; S4 SEGMENT; CYSTATIN-B; DISEASE; FREQUENCY; FRAMEWORK; ONSET AB Progressive myoclonus epilepsies (PMEs) are a group of rare, inherited disorders manifesting with action myoclonus, tonicclonic seizures and ataxia. We sequenced the exomes of 84 unrelated individuals with PME of unknown cause and molecularly solved 26 cases (31%). Remarkably, a recurrent de novo mutation, c. 959G>A (p.Arg320His), in KCNC1 was identified as a new major cause for PME. Eleven unrelated exome-sequenced (13%) and two affected individuals in a secondary cohort (7%) had this mutation. KCNC1 encodes K(V)3.1, a subunit of the K(V)3 voltage-gated potassium ion channels, which are major determinants of high-frequency neuronal firing. Functional analysis of the Arg320His mutant channel showed a dominant-negative loss-of-function effect. Ten cases had pathogenic mutations in known PME-associated genes (NEU1, NHLRC1, AFG3L2, EPM2A, CLN6 and SERPINI1). Identification of mutations in PRNP, SACS and TBC1D24 expand their phenotypic spectra to PME. These findings provide insights into the molecular genetic basis of PME and show the role of de novo mutations in this disease entity. C1 [Muona, Mikko; Palotie, Aarno] Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland. [Muona, Mikko; Joensuu, Tarja; Markkinen, Salla; Lehesjoki, Anna-Elina] Folkhalsan Inst Genet, Helsinki, Finland. [Muona, Mikko; Joensuu, Tarja; Markkinen, Salla; Lehesjoki, Anna-Elina] Univ Helsinki, Ctr Neurosci, Helsinki, Finland. [Muona, Mikko; Joensuu, Tarja; Markkinen, Salla; Lehesjoki, Anna-Elina] Univ Helsinki, Res Programs Unit, Helsinki, Finland. [Berkovic, Samuel F.; Oliver, Karen L.; Hildebrand, Michael S.; Scheffer, Ingrid E.] Univ Melbourne, Epilepsy Res Ctr, Dept Med, Austin Hlth, Heidelberg, Vic, Australia. [Dibbens, Leanne M.; Bayly, Marta A.; Heron, Sarah E.] Univ S Australia, Sch Pharm & Med Sci, Adelaide, SA 5001, Australia. [Maljevic, Snezana; Lerche, Holger] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurol & Epileptol, Tubingen, Germany. [Canafoglia, Laura; Franceschetti, Silvana] IRCCS, C Besta Fdn Neurol Inst, Dept Neurophysiopathol, Milan, Italy. [Michelucci, Roberto; Tinuper, Paolo; Licchetta, Laura; Riguzzi, Patrizia] IRCCS, Bellaria Hosp, Inst Neurol Sci Bologna, Neurol Unit, Bologna, Italy. [Andermann, Eva; Andermann, Frederick] McGill Univ, Montreal Neurol Inst, Quebec City, PQ, Canada. [Gambardella, Antonio] Magna Graecia Univ Catanzaro, Inst Neurol, Catanzaro, Italy. [Tinuper, Paolo; Licchetta, Laura] Univ Bologna, Dept Biomed & Neuromotor Sci, Bologna, Italy. [Scheffer, Ingrid E.; Petrou, Steven] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Melbourne, Vic, Australia. [Scheffer, Ingrid E.] Univ Melbourne, Royal Childrens Hosp, Dept Pediat, Melbourne, Vic, Australia. [Criscuolo, Chiara; Filla, Alessandro] Univ Naples Federico II, Dept Neurosci Reprod Sci & Odontostomatol, Naples, Italy. [Ferlazzo, Edoardo] Magna Graecia Univ Catanzaro, Dept Med & Surg Sci, Catanzaro, Italy. [Ferlazzo, Edoardo] Bianchi Melacrino Morelli Hosp, Reg Epilepsy Ctr, Reggio Di Calabria, Italy. [Ahmad, Jamil] Balochistan Univ Informat Technol Engn & Manageme, Dept Biotechnol & Informat, Quetta, Pakistan. [Ahmad, Adeel] Mayo Hosp, Dept Med, Lahore, Pakistan. [Baykan, Betul] Istanbul Univ, Istanbul Fac Med, Dept Neurol, Istanbul, Turkey. [Baykan, Betul] Istanbul Univ, Epilepsy Ctr EPIMER, Istanbul, Turkey. [Said, Edith] Univ Malta, Dept Anat & Cell Biol, Msida, Malta. [Said, Edith] Mater Hosp, Sect Med Genet, Msida, Malta. [Topcu, Meral] Hacettepe Univ, Fac Med, Dept Pediat, Div Pediat Neurol, TR-06100 Ankara, Turkey. [King, Mary D.] Temple St Childrens Univ Hosp, Dept Neurol, Dublin, Ireland. [King, Mary D.] Univ Coll Dublin, Sch Med & Med Sci, Acad Ctr Rare Dis, Dublin 2, Ireland. [Ozkara, Cigdem] Istanbul Univ, Cerrahpasa Med Fac, Dept Neurol, Istanbul, Turkey. [Andrade, Danielle M.] Univ Toronto, Toronto Western Hosp, Dept Med, Krembil Neurosci Program, Toronto, ON M5T 2S8, Canada. [Engelsen, Bernt A.] Univ Bergen, Dept Clin Med, Bergen, Norway. [Engelsen, Bernt A.] Haukeland Hosp, Dept Neurol, N-5021 Bergen, Norway. [Crespel, Arielle] Hop Gui de Chauliac, Epilepsy Unit, Montpellier, France. [Lindenau, Matthias] Epilepsy Ctr Hamburg Alsterdorf, Dept Neurol & Epileptol, Hamburg, Germany. [Lohmann, Ebba] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, Tubingen, Germany. [Lohmann, Ebba] German Ctr Neurodegenerat Dis DZNE, Tubingen, Germany. [Saletti, Veronica] IRCCS, C Besta Fdn Neurol Inst, Dev Neurol Unit, Milan, Italy. [Massano, Joao] Ctr Hosp Sao Joao, Dept Neurol, Oporto, Portugal. [Massano, Joao] Univ Porto, Fac Med, Dept Clin Neurosci & Mental Hlth, P-4100 Oporto, Portugal. [Privitera, Michael] Univ Cincinnati, Epilepsy Ctr, Inst Neurosci, Cincinnati, OH USA. [Espay, Alberto J.] Univ Cincinnati, Gardner Ctr Parkinson Dis & Movement Disorders, Cincinnati, OH USA. [Kauffmann, Birgit] Klinikum Links Weser, Bremen, Germany. [Duchowny, Michael] Miami Childrens Hosp, Inst Brain, Miami, FL USA. [Duchowny, Michael] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. [Moller, Rikke S.] Danish Epilepsy Ctr, Dianalund, Denmark. [Moller, Rikke S.] Univ Southern Denmark, Inst Reg Hlth Serv Res, Odense, Denmark. [Straussberg, Rachel] Schneider Childrens Med Ctr Israel, Child Neurol Inst, Neurogenet Clin, Petah Tiqvah, Israel. [Straussberg, Rachel; Afawi, Zaid; Ben-Zeev, Bruria] Tel Aviv Univ, Sackler Sch Med, Ramat Aviv, Israel. [Afawi, Zaid] Ben Gurion Univ Negev, Zlotowski Ctr Neurosci, IL-84105 Beer Sheva, Israel. [Ben-Zeev, Bruria] Edmond & Lilly Safra Childrens Hosp, Sheba Med Ctr, Pediatr Neurol Unit, Ramat Gan, Israel. [Samocha, Kaitlin E.; Daly, Mark J.; Palotie, Aarno] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Samocha, Kaitlin E.; Daly, Mark J.; Palotie, Aarno] Harvard Univ, Sch Med, Boston, MA USA. [Samocha, Kaitlin E.; Daly, Mark J.; Palotie, Aarno] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Samocha, Kaitlin E.; Daly, Mark J.; Palotie, Aarno] MIT, Cambridge, MA 02139 USA. [Samocha, Kaitlin E.; Daly, Mark J.; Palotie, Aarno] Broad Inst Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Samocha, Kaitlin E.] Harvard Univ, Sch Med, Program Genet & Genom Biol & Biomed Sci, Boston, MA USA. [Petrou, Steven] Univ Melbourne, Ctr Neural Engn, Melbourne, Vic, Australia. [Palotie, Aarno] Wellcome Trust Genome Campus, Wellcome Trust Sanger Inst, Hinxton, England. [Palotie, Aarno] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Palotie, Aarno] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Lehesjoki, AE (reprint author), Folkhalsan Inst Genet, Helsinki, Finland. EM anna-elina.lehesjoki@helsinki.fi RI Scheffer, Ingrid/G-1668-2013; Heron, Sarah/F-4222-2013; Canafoglia, Laura/K-4787-2016; OI Gambardella , Antonio/0000-0001-7384-3074; Massano, Joao/0000-0002-5791-7149; Scheffer, Ingrid/0000-0002-2311-2174; Heron, Sarah/0000-0001-8759-6748; Canafoglia, Laura/0000-0002-5385-761X; Oliver, Karen/0000-0001-5188-6153; Muona, Mikko/0000-0002-0949-6650; Michelucci, Roberto/0000-0002-9655-7940; Provini, Federica/0000-0001-9063-2658; Berkovic, Samuel/0000-0003-4580-841X; tinuper, paolo/0000-0002-0588-3063 FU Folkhalsan Research Foundation; Academy of Finland [251704, 263401, 141549]; Wellcome Trust [089062, 098051]; European Commission Framework Programme 7 (FP7) [201413, 242167, 261433, 261123]; Sigrid Juselius Foundation; US NIH [RFA-HL-12-007]; Emil Aaltonen Foundation; Epilepsiatutkimussaatio; University of Helsinki Funds; Doctoral Programme in Biomedicine; National Health and Medical Research Council (NHMRC) of Australia [628952]; NHMRC Career Development Fellowship [1032603]; NHMRC Early Career Fellowship [1016715]; German Network for Rare Diseases of the Federal Ministry of Education and Research (BMBF); IonNeurONet [01GM1105A]; EuroEPINOMICS program of the European Science Foundation; German Research Foundation (DFG) [Le1030/11-1]; NHMRC [400121]; NMHRC [1005050]; state of Victoria FX This study was supported by the Folkhalsan Research Foundation (A.-E.L.), Academy of Finland grant 141549 (A.-E.L.), Wellcome Trust grants 089062 and 098051 (A.P.), European Commission Framework Programme 7 (FP7) project 201413 ENGAGE (A.P.), project 242167 SynSys (A.P.), Health-2010 projects 261433 BioSHare (A.P.) and project 261123 gEUVADIS (A.P.), Academy of Finland grants 251704 and 263401 (A.P.), the Sigrid Juselius Foundation (A.P.), US NIH grant RFA-HL-12-007 (A.P.), the Emil Aaltonen Foundation (M.M.), Epilepsiatutkimussaatio (M.M.), University of Helsinki Funds (M.M.), the Doctoral Programme in Biomedicine (M.M.), National Health and Medical Research Council (NHMRC) of Australia program grant 628952 (S.F.B., L.M.D. and I.E.S.), NHMRC Career Development Fellowship 1032603 (L.M.D.), NHMRC Early Career Fellowship 1016715 (S.E.H.), the German Network for Rare Diseases of the Federal Ministry of Education and Research (BMBF), IonNeurONet 01GM1105A (S. Maljevic and H.L.), the EuroEPINOMICS program of the European Science Foundation, German Research Foundation (DFG) grant Le1030/11-1 (H.L. and S. Maljevic), NHMRC program grant 400121 (S.P.) and NMHRC fellowship 1005050 (S.P.). The Florey Institute of Neuroscience and Mental Health (S.P.) is supported by government infrastructure funds from the state of Victoria. NR 79 TC 45 Z9 46 U1 6 U2 32 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD JAN PY 2015 VL 47 IS 1 BP 39 EP + DI 10.1038/ng.3144 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA AX5TM UT WOS:000346990400009 PM 25401298 ER PT J AU Wainger, BJ Buttermore, ED Oliveira, JT Mellin, C Lee, S Saber, WA Wang, AJ Ichida, JK Chiu, IM Barrett, L Huebner, EA Bilgin, C Tsujimoto, N Brenneis, C Kapur, K Rubin, LL Eggan, K Woolf, CJ AF Wainger, Brian J. Buttermore, Elizabeth D. Oliveira, Julia T. Mellin, Cassidy Lee, Seungkyu Saber, Wardiya Afshar Wang, Amy J. Ichida, Justin K. Chiu, Isaac M. Barrett, Lee Huebner, Eric A. Bilgin, Canan Tsujimoto, Naomi Brenneis, Christian Kapur, Kush Rubin, Lee L. Eggan, Kevin Woolf, Clifford J. TI Modeling pain in vitro using nociceptor neurons reprogrammed from fibroblasts SO NATURE NEUROSCIENCE LA English DT Article ID ROOT GANGLION NEURONS; SENSORY NEURONS; FAMILIAL DYSAUTONOMIA; NEUROPATHIC PAIN; TRANSCRIPTION FACTORS; MEMBRANE-PROPERTIES; SODIUM-CHANNELS; NERVOUS-SYSTEM; DRG NEURONS; CELL FATES AB Reprogramming somatic cells from one cell fate to another can generate specific neurons suitable for disease modeling. To maximize the utility of patient-derived neurons, they must model not only disease-relevant cell classes, but also the diversity of neuronal subtypes found in vivo and the pathophysiological changes that underlie specific clinical diseases. We identified five transcription factors that reprogram mouse and human fibroblasts into noxious stimulus-detecting (nociceptor) neurons. These recapitulated the expression of quintessential nociceptor-specific functional receptors and channels found in adult mouse nociceptor neurons, as well as native subtype diversity. Moreover, the derived nociceptor neurons exhibited TrpV1 sensitization to the inflammatory mediator prostaglandin E2 and the chemotherapeutic drug oxaliplatin, modeling the inherent mechanisms underlying inflammatory pain hypersensitivity and painful chemotherapy-induced neuropathy. Using fibroblasts from patients with familial dysautonomia (hereditary sensory and autonomic neuropathy type III), we found that the technique was able to reveal previously unknown aspects of human disease phenotypes in vitro. C1 [Wainger, Brian J.; Buttermore, Elizabeth D.; Oliveira, Julia T.; Mellin, Cassidy; Lee, Seungkyu; Saber, Wardiya Afshar; Wang, Amy J.; Chiu, Isaac M.; Barrett, Lee; Huebner, Eric A.; Bilgin, Canan; Brenneis, Christian; Kapur, Kush; Woolf, Clifford J.] Boston Childrens Hosp, FM Kirby Neurobiol Ctr, Cambridge, MA 02142 USA. [Wainger, Brian J.; Buttermore, Elizabeth D.; Oliveira, Julia T.; Mellin, Cassidy; Lee, Seungkyu; Saber, Wardiya Afshar; Wang, Amy J.; Chiu, Isaac M.; Barrett, Lee; Huebner, Eric A.; Bilgin, Canan; Brenneis, Christian; Kapur, Kush; Woolf, Clifford J.] Harvard Stem Cell Inst, Cambridge, MA USA. [Wainger, Brian J.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Wainger, Brian J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Wainger, Brian J.; Buttermore, Elizabeth D.; Lee, Seungkyu; Chiu, Isaac M.; Huebner, Eric A.; Woolf, Clifford J.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Oliveira, Julia T.] Univ Fed Rio de Janeiro, Fac Med, Dept Patol, Lab Neurodegeneracao & Reparo, Rio De Janeiro, Brazil. [Ichida, Justin K.; Tsujimoto, Naomi; Rubin, Lee L.; Eggan, Kevin] Harvard Univ, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Ichida, Justin K.] Univ So Calif, Dept Stem Cell Biol & Regenerat Med, Eli & Edythe Broad, Los Angeles, CA USA. [Ichida, Justin K.] Univ So Calif, CIRM Ctr Regenerat Med, Stem Cell Res, Los Angeles, CA USA. [Eggan, Kevin] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. RP Woolf, CJ (reprint author), Boston Childrens Hosp, FM Kirby Neurobiol Ctr, Cambridge, MA 02142 USA. EM clifford.woolf@childrens.harvard.edu FU National Institute of General Medical Sciences [T32 GM07592]; National Institute of Neurological Disorders and Stroke [1K08-NS082364, NS038253]; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico; GlaxoSmithKline Regenerative Medicine DPU; Dr. Miriam and Sheldon G. Adelson Medical Foundation FX We thank M. Costigan for assistance with RT-PCR, A. Yekkirala and J. Sprague for help with calcium imaging, Q. Ma (Dana-Farber Cancer Institute) and E. Turner (Seattle Children's Research Institute) for constructs, J. Gardner and J. McNeish for helpful advice and support, and K. Wainger for assistance with figure preparation. We also thank the Boston Children's Hospital IDDRC Molecular Genetics Core Facility for RNA Bioanalyzer analyses and the Harvard Medical School ICCB Screening Facility for assistance with ImageXpress and MetaXpress analyses. This research was supported by the National Institute of General Medical Sciences (T32 GM07592) and National Institute of Neurological Disorders and Stroke (1K08-NS082364) to B.J.W. Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (J.T.O.), GlaxoSmithKline Regenerative Medicine DPU (C.J.W.), the National Institute of Neurological Disorders and Stroke (NS038253 to C.J.W.), and the Dr. Miriam and Sheldon G. Adelson Medical Foundation (C.J.W.). NR 59 TC 31 Z9 32 U1 4 U2 32 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 EI 1546-1726 J9 NAT NEUROSCI JI Nat. Neurosci. PD JAN PY 2015 VL 18 IS 1 BP 17 EP + DI 10.1038/nn.3886 PG 10 WC Neurosciences SC Neurosciences & Neurology GA AX5WH UT WOS:000346995000007 PM 25420066 ER PT J AU Jain, N Walker, WA AF Jain, Nitya Walker, W. Allan TI Diet and host-microbial crosstalk in postnatal intestinal immune homeostasis SO NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY LA English DT Review ID INFLAMMATORY-BOWEL-DISEASE; BREAST-FED INFANTS; INNATE LYMPHOID-CELLS; FORMULA-FED INFANTS; REGULATORY T-CELLS; SEGMENTED FILAMENTOUS BACTERIA; HUMAN GUT MICROBIOME; EARLY-LIFE; TIGHT JUNCTIONS; EPITHELIAL-CELLS AB Neonates face unique challenges in the period following birth. The postnatal immune system is in the early stages of development and has a range of functional capabilities that are distinct from the mature adult immune system. Bidirectional immune-microbial interactions regulate the development of mucosal immunity and alter the composition of the microbiota, which contributes to overall host well-being. In the past few years, nutrition has been highlighted as a third element in this interaction that governs host health by modulating microbial composition and the function of the immune system. Dietary changes and imbalances can disturb the immune-microbiota homeostasis, which might alter susceptibility to several autoimmune and metabolic diseases. Major changes in cultural traditions, socioeconomic status and agriculture are affecting the nutritional status of humans worldwide, which is altering core intestinal microbial communities. This phenomenon is especially relevant to the neonatal and paediatric populations, in which the microbiota and immune system are extremely sensitive to dietary influences. In this Review, we discuss the current state of knowledge regarding early-life nutrition, its effects on the microbiota and the consequences of diet-induced perturbation of the structure of the microbial community on mucosal immunity and disease susceptibility. C1 [Jain, Nitya] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Walker, W. Allan] Massachusetts Gen Hosp, Mucosal Immunol & Biol Res Ctr, Charlestown, MA 02129 USA. RP Jain, N (reprint author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, 185 Cambridge St, Boston, MA 02114 USA. EM njain@ccib.mgh.harvard.edu FU Charles King Trust/Charles Hood Foundation Postdoctoral Fellowship Award; [P30 DK040561]; [P01 DK33506]; [R01 HD012447]; [R01 HD059126] FX N.J. would like to acknowledge the support of the Charles King Trust/Charles Hood Foundation Postdoctoral Fellowship Award. W.A.W. would like to acknowledge the support of grants P30 DK040561, P01 DK33506, R01 HD012447 and R01 HD059126. NR 168 TC 14 Z9 14 U1 3 U2 55 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5045 EI 1759-5053 J9 NAT REV GASTRO HEPAT JI Nat. Rev. Gastroenterol. Hepatol. PD JAN PY 2015 VL 12 IS 1 BP 14 EP 25 DI 10.1038/nrgastro.2014.153 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AX5IE UT WOS:000346958900006 PM 25201040 ER PT J AU Tache, Y AF Tache, Y. TI Corticotrophin-releasing factor 1 activation in the central amygdale and visceral hyperalgesia SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Review DE central amygdala; CRF; CRF1; antagonists; noradrenaline; stress; visceral hyperalgesia ID IRRITABLE-BOWEL-SYNDROME; FACTOR-I RECEPTORS; STRESS-RELATED ALTERATIONS; CENTRAL NUCLEUS; COLONIC HYPERSENSITIVITY; COLORECTAL DISTENSION; FACTOR CRF; PSYCHOLOGICAL STRESS; MEDIATED MECHANISMS; RECTAL DISTENSION AB Corticotropin-releasing factor (CRF)-CRF1 receptor in the brain plays a key role in stress-related alterations of behavior including anxiety/depression, and autonomic and visceral functions. In particular, CRF1 signaling mediates hypersensitivity to colorectal distension (CRD) in various models (early life adverse events, repeated psychological stress, chronic high anxiety, postcolonic inflammation, or repeated nociceptive CRD). So far, knowledge of brain sites involved is limited. A recent article demonstrates in rats that CRF microinjected into the central amygdala (CeA) induces a hyperalgesic response to CRD and enhances the noradrenaline and dopamine levels at this site. The visceral and noradrenaline, unlike dopamine, responses were blocked by a CRF1 antagonist injected into the CeA. Here, we review the emerging role that CRF-CRF1 signaling plays in the CeA to induce visceral hypersensitivity. In the somatic pain field, CRF in the CeA was shown to induce pain sensitization. This is mediated by the activation of postsynaptic CRF1 receptors and protein kinase A signaling that increases N-methyl-d-aspartate receptor neurotransmission. In addition, the activation of tetraethylamonium-sensitive ion channels such as Kv3 accelerates repolarization and firing rate. Whether facilitation of pain transmission underlies CRF action in the CeA-induced visceral hypersensitivity will need to be delineated. CRF1 signaling in the CeA is also an important component of the neuronal circuitry inducing anxiety-like behavior and positioned at the interphase of the reciprocal relationship between pain and affective state. The hyperactivity of this system may represent the neuroanatomical and biochemical substrate contributing to the coexpression of hypersensitivity to CRD and mood disorders in subsets of irritable bowel syndrome patients. This review describes the role of CRF-CRF1 receptor signaling in experimental models of visceral hyperalgesia with a focus on brain sites and mechanisms of action in the central amygdala. C1 [Tache, Y.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurobiol Stress & Womens Hlth, Los Angeles, CA 90095 USA. [Tache, Y.] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA. [Tache, Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Tache, Y (reprint author), VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU Veterans Administration Research Career Scientist Award; [NIHDDK-41303]; [NIHDDK-57238] FX Supported by NIHDDK-41303 (Animal core), NIHDDK-57238, and Veterans Administration Research Career Scientist Award. NR 64 TC 6 Z9 6 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1350-1925 EI 1365-2982 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD JAN PY 2015 VL 27 IS 1 BP 1 EP 6 DI 10.1111/nmo.12495 PG 6 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA AX8NX UT WOS:000347167100001 PM 25557223 ER PT J AU Berkhemer, OA Fransen, PSS Beumer, D van den Berg, LA Lingsma, HF Yoo, AJ Schonewille, WJ Vos, JA Nederkoorn, PJ Wermer, MJH van Walderveen, MAA Staals, J Hofmeijer, J van Oostayen, JA Nijeholt, GJLA Boiten, J Brouwer, PA Emmer, BJ de Bruijn, SF van Dijk, LC Kappelle, LJ Lo, RH Van Dijk, EJ de Vries, J de Kort, PLM van Rooij, WJJ van den Berg, JSP van Hasselt, BAAM Aerden, LAM Dallinga, RJ Visser, MC Bot, JCJ Vroomen, PC Eshghi, O Schreuder, THCML Heijboer, RJJ Keizer, K Tielbeek, AV den Hertog, HM Gerrits, DG van den Berg-Vos, RM Karas, GB Steyerberg, EW Flach, HZ Marquering, HA Sprengers, MES Jenniskens, SFM Beenen, LFM van den Berg, R Koudstaal, PJ van Zwam, WH Roos, YBWEM van der Lugt, A van Oostenbrugge, RJ Majoie, CBLM Dippel, DWJ AF Berkhemer, O. A. Fransen, P. S. S. Beumer, D. van den Berg, L. A. Lingsma, H. F. Yoo, A. J. Schonewille, W. J. Vos, J. A. Nederkoorn, P. J. Wermer, M. J. H. van Walderveen, M. A. A. Staals, J. Hofmeijer, J. van Oostayen, J. A. Nijeholt, G. J. Lycklama A. Boiten, J. Brouwer, P. A. Emmer, B. J. de Bruijn, S. F. van Dijk, L. C. Kappelle, L. J. Lo, R. H. Van Dijk, E. J. de Vries, J. de Kort, P. L. M. van Rooij, W. J. J. van den Berg, J. S. P. van Hasselt, B. A. A. M. Aerden, L. A. M. Dallinga, R. J. Visser, M. C. Bot, J. C. J. Vroomen, P. C. Eshghi, O. Schreuder, T. H. C. M. L. Heijboer, R. J. J. Keizer, K. Tielbeek, A. V. den Hertog, H. M. Gerrits, D. G. van den Berg-Vos, R. M. Karas, G. B. Steyerberg, E. W. Flach, H. Z. Marquering, H. A. Sprengers, M. E. S. Jenniskens, S. F. M. Beenen, L. F. M. van den Berg, R. Koudstaal, P. J. van Zwam, W. H. Roos, Y. B. W. E. M. van der Lugt, A. van Oostenbrugge, R. J. Majoie, C. B. L. M. Dippel, D. W. J. CA MR CLEAN Investigators TI A Randomized Trial of Intraarterial Treatment for Acute Ischemic Stroke SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ENDOVASCULAR TREATMENT; CEREBRAL INFARCT; THERAPY; RECANALIZATION; OCCLUSIONS; SCORE AB BACKGROUND In patients with acute ischemic stroke caused by a proximal intracranial arterial occlusion, intraarterial treatment is highly effective for emergency revascularization. However, proof of a beneficial effect on functional outcome is lacking. METHODS We randomly assigned eligible patients to either intraarterial treatment plus usual care or usual care alone. Eligible patients had a proximal arterial occlusion in the anterior cerebral circulation that was confirmed on vessel imaging and that could be treated intraarterially within 6 hours after symptom onset. The primary outcome was the modified Rankin scale score at 90 days; this categorical scale measures functional outcome, with scores ranging from 0 (no symptoms) to 6 (death). The treatment effect was estimated with ordinal logistic regression as a common odds ratio, adjusted for prespecified prognostic factors. The adjusted common odds ratio measured the likelihood that intraarterial treatment would lead to lower modified Rankin scores, as compared with usual care alone (shift analysis). RESULTS We enrolled 500 patients at 16 medical centers in the Netherlands (233 assigned to intraarterial treatment and 267 to usual care alone). The mean age was 65 years (range, 23 to 96), and 445 patients (89.0%) were treated with intravenous alteplase before randomization. Retrievable stents were used in 190 of the 233 patients (81.5%) assigned to intraarterial treatment. The adjusted common odds ratio was 1.67 (95% confidence interval [CI], 1.21 to 2.30). There was an absolute difference of 13.5 percentage points (95% CI, 5.9 to 21.2) in the rate of functional independence (modified Rankin score, 0 to 2) in favor of the intervention (32.6% vs. 19.1%). There were no significant differences in mortality or the occurrence of symptomatic intracerebral hemorrhage. CONCLUSIONS In patients with acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation, intraarterial treatment administered within 6 hours after stroke onset was effective and safe. (Funded by the Dutch Heart Foundation and others; MR CLEAN Netherlands Trial Registry number, NTR1804, and Current Controlled Trials number, ISRCTN10888758.) C1 [Berkhemer, O. A.; Marquering, H. A.; Sprengers, M. E. S.; Beenen, L. F. M.; van den Berg, R.; Majoie, C. B. L. M.] Univ Amsterdam, Acad Med Ctr, Dept Radiol, NL-1105 AZ Amsterdam, Netherlands. [van den Berg, L. A.; Nederkoorn, P. J.; Roos, Y. B. W. E. M.] Univ Amsterdam, Acad Med Ctr, Dept Neurol, NL-1105 AZ Amsterdam, Netherlands. [Marquering, H. A.] Univ Amsterdam, Acad Med Ctr, Dept Biomed Engn & Phys, NL-1105 AZ Amsterdam, Netherlands. [Visser, M. C.] Vrije Univ Amsterdam Med Ctr, Dept Neurol, Amsterdam, Netherlands. [Bot, J. C. J.] Vrije Univ Amsterdam Med Ctr, Dept Radiol, Amsterdam, Netherlands. [van den Berg-Vos, R. M.] Sint Lucas Andreas Hosp, Dept Neurol, Amsterdam, Netherlands. [Karas, G. B.] Sint Lucas Andreas Hosp, Dept Radiol, Amsterdam, Netherlands. [Berkhemer, O. A.; Fransen, P. S. S.; Beumer, D.; Koudstaal, P. J.; Dippel, D. W. J.] Erasmus Univ, Med Ctr, Dept Neurol, Rotterdam, Netherlands. [Fransen, P. S. S.; Brouwer, P. A.; Emmer, B. J.; van der Lugt, A.] Erasmus Univ, Med Ctr, Dept Radiol, Rotterdam, Netherlands. [Lingsma, H. F.; Steyerberg, E. W.] Erasmus Univ, Med Ctr, Dept Publ Hlth, Rotterdam, Netherlands. [Beumer, D.; Staals, J.; van Oostenbrugge, R. J.] Maastricht Univ, Med Ctr, Dept Neurol, Maastricht, Netherlands. [Beumer, D.; Staals, J.; van Oostenbrugge, R. J.] Cardiovasc Res Inst Maastricht, Maastricht, Netherlands. [van Zwam, W. H.] Maastricht Univ, Med Ctr, Dept Radiol, Maastricht, Netherlands. [Schonewille, W. J.] St Antonius Hosp, Dept Neurol, Nieuwegein, Netherlands. [Vos, J. A.] St Antonius Hosp, Dept Radiol, Nieuwegein, Netherlands. [Wermer, M. J. H.] Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands. [van Walderveen, M. A. A.] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands. [Hofmeijer, J.] Rijnstate Hosp, Dept Neurol, Arnhem, Netherlands. [van Oostayen, J. A.] Rijnstate Hosp, Dept Radiol, Arnhem, Netherlands. [Nijeholt, G. J. Lycklama A.] MC Haaglanden, Dept Radiol, The Hague, Netherlands. [Boiten, J.] MC Haaglanden, Dept Neurol, The Hague, Netherlands. [de Bruijn, S. F.] HAGA Hosp, Dept Neurol, The Hague, Netherlands. [van Dijk, L. C.] HAGA Hosp, Dept Radiol, The Hague, Netherlands. [Kappelle, L. J.] Univ Med Ctr Utrecht, Dept Neurol, Utrecht, Netherlands. [Kappelle, L. J.] Univ Med Ctr Utrecht, Dept Neurol, Utrecht, Netherlands. [Lo, R. H.] Univ Med Ctr Utrecht, Dept Radiol, Utrecht, Netherlands. [Van Dijk, E. J.] Radboud Univ Nijmegen, Med Ctr, Dept Neurol, NL-6525 ED Nijmegen, Netherlands. [de Vries, J.] Radboud Univ Nijmegen, Med Ctr, Dept Neurosurg, NL-6525 ED Nijmegen, Netherlands. [Jenniskens, S. F. M.] Radboud Univ Nijmegen, Med Ctr, Dept Radiol, NL-6525 ED Nijmegen, Netherlands. [de Kort, P. L. M.] Sint Elisabeth Hosp, Dept Neurol, Tilburg, Netherlands. [van Rooij, W. J. J.] Sint Elisabeth Hosp, Dept Radiol, Tilburg, Netherlands. [van den Berg, J. S. P.] Isala Klin, Dept Neurol, Zwolle, Netherlands. [van Hasselt, B. A. A. M.; Flach, H. Z.] Isala Klin, Dept Radiol, Zwolle, Netherlands. [Aerden, L. A. M.] Reinier Graaf Gasthuis, Dept Neurol, Delft, Netherlands. [Dallinga, R. J.] Reinier Graaf Gasthuis, Dept Radiol, Delft, Netherlands. [Vroomen, P. C.] Univ Groningen, Univ Med Ctr Groningen, Dept Neurol, NL-9713 AV Groningen, Netherlands. [Eshghi, O.] Univ Groningen, Univ Med Ctr Groningen, Dept Radiol, NL-9713 AV Groningen, Netherlands. [Schreuder, T. H. C. M. L.] Atrium Med Ctr, Dept Neurol, Heerlen, Netherlands. [Heijboer, R. J. J.] Atrium Med Ctr, Dept Radiol, Heerlen, Netherlands. [Keizer, K.] Catharina Hosp, Dept Neurol, Eindhoven, Netherlands. [Tielbeek, A. V.] Catharina Hosp, Dept Radiol, Eindhoven, Netherlands. [den Hertog, H. M.] Med Spectrum Twente, Dept Neurol, Enschede, Netherlands. [Gerrits, D. G.] Med Spectrum Twente, Dept Radiol, Enschede, Netherlands. [Yoo, A. J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Dippel, DWJ (reprint author), Erasmus MC Univ Med Ctr, Dept Neurol H643, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM d.dippel@erasmusmc.nl RI van Dijk, Ewoud/J-7951-2012; Jenniskens, S.F.M./L-4415-2015; OI Santos, Emilie/0000-0003-2153-1938 FU Dutch Heart Foundation; AngioCare Covidien/ev3; Medac/Lamepro; Penumbra; Stryker; BALT; Toshiba; Codman/DePuy Synthes; Sequent Medical; Covidien/ev3 FX Supported by the Dutch Heart Foundation and by unrestricted grants from AngioCare Covidien/ev3, Medac/Lamepro, and Penumbra.; Dr. Yoo reports receiving grant support from Penumbra; Dr. Brouwer, lecture fees and fees for trial management from Stryker, lecture fees and fees for proctoring from BALT, lecture fees from Toshiba, teaching fees and fees for research and development from Codman/DePuy Synthes, and teaching fees from Sequent Medical; Dr. de Vries, consulting fees from Stryker and grant support from Covidien/ev3; and Dr. Ren van den Berg, consulting fees from Codman/DePuy Synthes. No other potential conflict of interest relevant to this article was reported. NR 29 TC 893 Z9 927 U1 32 U2 116 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 JAN 1 PY 2015 VL 372 IS 1 BP 11 EP 20 DI 10.1056/NEJMoa1411587 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AX7MU UT WOS:000347100800005 PM 25517348 ER PT J AU Robert, C Karaszewska, B Schachter, J Rutkowski, P Mackiewicz, A Stroiakovski, D Lichinitser, M Dummer, R Grange, F Mortier, L Chiarion-Sileni, V Drucis, K Krajsova, I Hauschild, A Lorigan, P Wolter, P Long, GV Flaherty, K Nathan, P Ribas, A Martin, AM Sun, P Crist, W Legos, J Rubin, SD Little, SM Schadendorf, D AF Robert, Caroline Karaszewska, Boguslawa Schachter, Jacob Rutkowski, Piotr Mackiewicz, Andrzej Stroiakovski, Daniil Lichinitser, Michael Dummer, Reinhard Grange, Florent Mortier, Laurent Chiarion-Sileni, Vanna Drucis, Kamil Krajsova, Ivana Hauschild, Axel Lorigan, Paul Wolter, Pascal Long, Georgina V. Flaherty, Keith Nathan, Paul Ribas, Antoni Martin, Anne-Marie Sun, Peng Crist, Wendy Legos, Jeff Rubin, Stephen D. Little, Shonda M. Schadendorf, Dirk TI Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BRAF-MUTATED MELANOMA; METASTATIC MELANOMA; ACQUIRED-RESISTANCE; MEK INHIBITION; RAF INHIBITION; V600E MUTATION; VEMURAFENIB; OVERCOME; CRITERIA; TUMORS AB BACKGROUND The BRAF inhibitors vemurafenib and dabrafenib have shown efficacy as mono-therapies in patients with previously untreated metastatic melanoma with BRAF V600E or V600K mutations. Combining dabrafenib and the MEK inhibitor trametinib, as compared with dabrafenib alone, enhanced antitumor activity in this population of patients. METHODS In this open-label, phase 3 trial, we randomly assigned 704 patients with metastatic melanoma with a BRAF V600 mutation to receive either a combination of dabrafenib (150 mg twice daily) and trametinib (2 mg once daily) or vemurafenib (960 mg twice daily) orally as first-line therapy. The primary end point was overall survival. RESULTS At the preplanned interim overall survival analysis, which was performed after 77% of the total number of expected events occurred, the overall survival rate at 12 months was 72% (95% confidence interval [CI], 67 to 77) in the combination-therapy group and 65% (95% CI, 59 to 70) in the vemurafenib group (hazard ratio for death in the combination-therapy group, 0.69; 95% CI, 0.53 to 0.89; P = 0.005). The prespecified interim stopping boundary was crossed, and the study was stopped for efficacy in July 2014. Median progression-free survival was 11.4 months in the combination-therapy group and 7.3 months in the vemurafenib group (hazard ratio, 0.56; 95% CI, 0.46 to 0.69; P< 0.001). The objective response rate was 64% in the combination-therapy group and 51% in the vemurafenib group (P< 0.001). Rates of severe adverse events and study-drug discontinuations were similar in the two groups. Cutaneous squamous-cell carcinoma and keratoacanthoma occurred in 1% of patients in the combination-therapy group and 18% of those in the vemurafenib group. CONCLUSIONS Dabrafenib plus trametinib, as compared with vemurafenib monotherapy, significantly improved overall survival in previously untreated patients with metastatic melanoma with BRAF V600E or V600K mutations, without increased overall toxicity. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT01597908.) C1 [Robert, Caroline] Gustave Roussy, Villejuif, France. [Robert, Caroline] INSERM, U981, Villejuif, France. [Grange, Florent] CHU Reims, Hop Robert Debre, Reims, France. [Mortier, Laurent] CHU Lille, Hop Claude Huriez, F-59037 Lille, France. [Karaszewska, Boguslawa] Przychodnia Lekarska Komed, Konin, Poland. [Rutkowski, Piotr] Maria Sklodowska Curie Mem Canc Ctr, Warsaw, Poland. [Rutkowski, Piotr] Inst Oncol, Warsaw, Poland. [Mackiewicz, Andrzej] Poznan Univ Med Sci, Med Polonia, Poznan, Poland. [Drucis, Kamil] Swissmed Ctr Zdrowia, Gdansk, Poland. [Drucis, Kamil] Med Univ Gdansk, Gdansk, Poland. [Schachter, Jacob] Chaim Sheba Med Ctr, Ramat, Israel. [Stroiakovski, Daniil] Moscow City Oncol Hosp 62, Moscow, Russia. [Lichinitser, Michael] Russian Acad Med Sci, Canc Res Ctr, Moscow, Russia. [Dummer, Reinhard] Univ Zurich, Zurich, Switzerland. [Chiarion-Sileni, Vanna] Ist Ricovero & Cura Carattere Sci, Ist Oncol Veneto, Padua, Italy. [Krajsova, Ivana] Gen Univ Hosp, Dermatooncol Dept, Prague, Czech Republic. [Hauschild, Axel] Univ Klinikum Schleswig Holstein, Kiel, Germany. [Stroiakovski, Daniil] Univ Hosp Essen, Essen, Germany. [Lorigan, Paul] Christie NHS Fdn Trust, Manchester, Lancs, England. [Nathan, Paul] Mt Vernon Canc Ctr, Northwood, Middx, England. [Wolter, Pascal] Univ Hosp Leuven, Leuven Canc Inst, Leuven, Belgium. [Long, Georgina V.] Univ Sydney, Melanoma Inst Australia, Mater Hosp, Sydney, NSW 2006, Australia. [Flaherty, Keith] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Ribas, Antoni] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Martin, Anne-Marie; Sun, Peng; Crist, Wendy; Legos, Jeff; Rubin, Stephen D.; Little, Shonda M.] GlaxoSmithKline Oncol Res & Dev, Collegeville, PA USA. RP Robert, C (reprint author), Gustave Roussy, Serv Dermatol, 114 Rue Edouard Vaillant, F-94805 Villejuif, France. EM caroline.robert@gustaveroussy.fr RI Lorigan, Paul/J-6898-2015; OI Lorigan, Paul/0000-0002-8875-2164; Drucis, Kamil/0000-0002-7251-3505; Rutkowski, Piotr/0000-0002-8920-5429 FU GlaxoSmithKline FX Supported by GlaxoSmithKline. NR 27 TC 420 Z9 425 U1 8 U2 41 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 JAN 1 PY 2015 VL 372 IS 1 BP 30 EP 39 DI 10.1056/NEJMoa1412690 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AX7MU UT WOS:000347100800007 PM 25399551 ER PT J AU Firth, PG AF Firth, Paul G. TI Health and Health Care in South Africa SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Firth, PG (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM pfirth@partners.org NR 2 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 1 PY 2015 VL 372 IS 1 BP 95 EP 95 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AX7MU UT WOS:000347100800026 PM 25551542 ER PT J AU Leffert, LR Clancy, CR Bateman, BT Bryant, AS Kuklina, EV AF Leffert, Lisa R. Clancy, Caitlin R. Bateman, Brian T. Bryant, Allison S. Kuklina, Elena V. TI Hypertensive Disorders and Pregnancy-Related Stroke Frequency, Trends, Risk Factors, and Outcomes SO OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the Society-for-Obstetric-Anesthesia-and-Perinatology CY MAY 14-18, 2014 CL Toronto, CANADA SP Soc Obstet Anesthesia & Perinatol ID HEALTH-CARE PROFESSIONALS; UNITED-STATES; INTRAVENOUS THROMBOLYSIS; MATERNAL MORBIDITY; HEMORRHAGIC STROKE; PREECLAMPSIA; HOSPITALIZATIONS; ASSOCIATION; PREVALENCE; ADULTS AB OBJECTIVE: To evaluate trends and associations of hypertensive disorders of pregnancy with stroke risk and test the hypothesis that hypertensive disorders of pregnancy-associated stroke results in higher rates of stroke-related complications than pregnancy-associated stroke without hypertensive disorders. METHODS: A cross-sectional study was performed using 81,983,216 pregnancy hospitalizations from the 1994-2011 Nationwide Inpatient Sample. Rates of stroke hospitalizations with and without these hypertensive disorders were reported per 10,000 pregnancy hospitalizations. Using logistic regression, adjusted odds ratios (OR) with 95% confidence intervals were obtained. RESULTS: Between 1994-1995 and 2010-2011, the nationwide rate of stroke with hypertensive disorders of pregnancy increased from 0.8 to 1.6 per 10,000 pregnancy hospitalizations (103%), whereas the rate without these disorders increased from 2.2 to 3.2 per 10,000 pregnancy hospitalizations (47%). Women with hypertensive disorders of pregnancy were 5.2 times more likely to have a stroke than those without. Having traditional stroke risk factors (eg, congenital heart disease, atrial fibrillation, sickle cell anemia, congenital coagulation defects) substantially increased the stroke risk among hypertensive disorders of pregnancy hospitalizations: from adjusted OR 2.68 for congenital coagulation defects to adjusted OR 13.1 for congenital heart disease. Stroke-related complications were increased in stroke with hypertensive disorders of pregnancy compared with without (from adjusted OR 1.23 for nonroutine discharge to adjusted OR 1.93 for mechanical ventilation). CONCLUSION: Having traditional stroke risk factors substantially increased the stroke risk among hypertensive disorders of pregnancy hospitalizations. Stroke with hypertensive disorders in pregnancy had two distinctive characteristics: a greater increase in frequency since themid-1990s and significantly higher stroke-related complication rates. C1 Massachusetts Gen Hosp, Dept Anesthesia, Obstet Anesthesia Div, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Reprod Hlth, Atlanta, GA USA. RP Leffert, LR (reprint author), Massachusetts Gen Hosp, Div Obstet Anesthesia, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM lleffert@partners.org FU Intramural CDC HHS [CC999999] NR 31 TC 14 Z9 15 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 EI 1873-233X J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JAN PY 2015 VL 125 IS 1 BP 124 EP 131 DI 10.1097/AOG.0000000000000590 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AX1WZ UT WOS:000346735600021 PM 25560114 ER PT J AU Cohen, SL Einarsson, JI Wang, KC Brown, D Boruta, D Scheib, SA Fader, AN Shibley, KA AF Cohen, Sarah L. Einarsson, Jon I. Wang, Karen C. Brown, Douglas Boruta, David Scheib, Stacey A. Fader, Amanda N. Shibley, K. A. TI Contained Power Morcellation Within an Insufflated Isolation Bag Reply SO OBSTETRICS AND GYNECOLOGY LA English DT Letter ID UTERINE LEIOMYOSARCOMA C1 [Cohen, Sarah L.; Einarsson, Jon I.; Wang, Karen C.] Brigham & Womens Hosp, Div Minimally Invas Gynecol Surg, Boston, MA 02115 USA. [Brown, Douglas; Boruta, David] Massachusetts Gen Hosp, Ctr Minimally Invas Gynecol Surg, Boston, MA 02114 USA. [Scheib, Stacey A.] Johns Hopkins Univ Hosp, Dept Gynecol & Obstet, Div Gynecol Specialties, Baltimore, MD 21287 USA. [Fader, Amanda N.; Shibley, K. A.] Johns Hopkins Univ Hosp, Dept Gynecol & Obstet, Kelly Gynecol Oncol Serv, Baltimore, MD 21287 USA. RP Cohen, SL (reprint author), Brigham & Womens Hosp, Div Minimally Invas Gynecol Surg, 75 Francis St, Boston, MA 02115 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 EI 1873-233X J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JAN PY 2015 VL 125 IS 1 BP 229 EP 230 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AX1WZ UT WOS:000346735600039 PM 25560132 ER PT J AU Walker, RJ Gebregziabher, M Martin-Harris, B Egede, LE AF Walker, Rebekah J. Gebregziabher, Mulugeta Martin-Harris, Bonnie Egede, Leonard E. TI Understanding the influence of psychological and socioeconomic factors on diabetes self-care using structured equation modeling SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Diabetes; Self-care; Psychosocial factors; Social determinants; Socioeconomic ID OF-THE-LITERATURE; PSYCHOMETRIC PROPERTIES; DEPRESSION; DISTRESS; VALIDITY; HEALTH; SCALE; METAANALYSIS; PERSPECTIVES; INSTRUMENT AB Objective: To develop and test latent variables of the social determinants of health that influence diabetes self-care. Methods: 615 adults with type 2 diabetes were recruited from two adult primary care clinics in the southeastern United States. Confirmatory factor analyses (CFA) identified the latent factors underlying socioeconomic determinants, psychosocial determinants, and self-care (diet, exercise, foot care, glucose testing, and medication adherence). Structured equation modeling (SEM) investigated the relationship between determinants and self-care. Results: Latent variables were created for diabetes self-care, psychological distress, self-efficacy, social support and social status. The initial model (chi2(254) = 388.04, p < 0.001, RMSEA = 0.03, CFI = 0.98) showed that lower psychological distress (r = -0.13, p = 0.019), higher social support (r = 0.15, p = 0.008), and higher self-efficacy (r = 0.47, p < 0.001) were significantly related to diabetes self-care. Social status was not significantly related to self-care (r = 0.003, p = 0.952). In the trimmed model (chi2(189) = 211.40, p = 0.126, RMSEA = 0.01, CFI = 0.99) lower psychological distress (r = -0.13, p = 0.016), higher social support (r = 0.15, p = 0.007), and higher self-efficacy (r = 0.47, p <0.001) remained significantly related to diabetes self-care. Conclusion: Based on theoretical relationships, three latent factors that measure social determinants of health (psychological distress, social support and self-efficacy) are strongly associated with diabetes self-care. Practice implications: This suggests that social determinants should be taken into account when developing patient self-care goals. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Walker, Rebekah J.; Gebregziabher, Mulugeta; Egede, Leonard E.] HEROIC, Charleston VA HSR&D COIN, Ralph H Johnson VAMC, Charleston, SC USA. [Walker, Rebekah J.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Walker, Rebekah J.; Martin-Harris, Bonnie] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Gebregziabher, Mulugeta] Med Univ S Carolina, Dept Med, Div Publ Hlth Sci, Charleston, SC 29425 USA. [Martin-Harris, Bonnie] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Egede, Leonard E.] Med Univ S Carolina, Dept Med, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280,POB 250593, Charleston, SC 29425 USA. EM egedel@musc.edu OI Gebregziabher, Mulugeta/0000-0002-4826-481X FU National Institute of Diabetes and Digestive and Kidney Disease [K24DK093699-01] FX This study was supported by Grant K24DK093699-01 from The National Institute of Diabetes and Digestive and Kidney Disease (PI: Leonard Egede). NR 47 TC 8 Z9 8 U1 0 U2 15 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD JAN PY 2015 VL 98 IS 1 BP 34 EP 40 DI 10.1016/j.pec.2014.10.002 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA AX5FO UT WOS:000346952400004 PM 25455793 ER PT J AU Fu, SS Roth, C Battaglia, CT Nelson, DB Farmer, MM Do, T Goldstein, MG Widome, R Hagedorn, H Zillich, AJ AF Fu, Steven S. Roth, Craig Battaglia, Catherine T. Nelson, David B. Farmer, Melissa M. Do, Tam Goldstein, Michael G. Widome, Rachel Hagedorn, Hildi Zillich, Alan J. TI Training primary care clinicians in motivational interviewing: A comparison of two models SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Motivational interviewing; Tobacco cessation; Primary care; Provider training ID TOBACCO CESSATION; RANDOMIZED-TRIAL; UNITED-STATES; COMPETENCE; STUDENTS; SMOKING; ADULTS; SCORES AB Objectives: To evaluate implementing two training models for motivational interviewing (MI) to address tobacco use with primary care clinicians. Methods: Clinicians were randomized to moderate or high intensity. Both training modalities included a single 1/2 day workshop facilitated by MI expert trainers. The high intensity (HI) training provided six booster sessions including telephone interactions with simulated patients and peer coaching by MI champions over 3 months. To assess performance of clinicians to deliver MI, an objective structured clinical evaluation (OSCE) was conducted before and 12 weeks after the workshop training. Results: Thirty-four clinicians were enrolled; 18 were randomly assigned to HI. Compared to the moderate intensity group, the HI group scored significantly higher during the OSCE for three of six global Motivational Interviewing Treatment Integrity scale scores. There was also significant improvement for three of the four measures of MI counseling knowledge, skills and confidence. Conclusions: Using champions and telephone interactions with simulated patients as enhancement strategies for MI training programs is feasible in the primary care setting and results in greater gains in MI proficiency. Practice implications: Results confirm and expand evidence for use of booster sessions to improve the proficiency of MI training programs for primary care clinicians. Published by Elsevier Ireland Ltd. C1 [Fu, Steven S.; Roth, Craig; Nelson, David B.; Do, Tam; Widome, Rachel; Hagedorn, Hildi] Minneapolis VA Healthcare Syst, Ctr Chron Dis Outcomes Res, Minneapolis, MN 55417 USA. [Fu, Steven S.; Roth, Craig; Nelson, David B.; Do, Tam; Widome, Rachel; Hagedorn, Hildi] Minneapolis VA Healthcare Syst, Gen Internal Med Sect, Minneapolis, MN 55417 USA. [Battaglia, Catherine T.] VA Eastern Colorado Hlth Care Syst, Denver Seattle Ctr Veteran Ctr & Value Driven Car, Denver, CO USA. [Battaglia, Catherine T.] Univ Colorado, Colorado Sch Publ Hlth, Denver, CO 80202 USA. [Farmer, Melissa M.] VA Greater Angeles Hlth Care Syst, Ctr Study Healthcare Innovat Implementat & Policy, Los Angeles, CA USA. [Goldstein, Michael G.] VHA Natl Ctr Hlth Promot & Dis, Durham, NH USA. [Zillich, Alan J.] Roudebush VA Med Ctr, Ctr Hlth Informat & Commun, Indianapolis, IN USA. [Zillich, Alan J.] Purdue Univ, Coll Pharm, W Lafayette, IN 47907 USA. RP Fu, SS (reprint author), Minneapolis VA Healthcare Syst, Ctr Chron Dis Outcomes Res, One Vet Dr 152, Minneapolis, MN 55417 USA. EM Steven.Fu@va.gov FU VA Health Services Research & Development (HSR&D) Rapid Response Project [11-019]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development and Health Services Research and Development; VA HSR&D Research Career Development Award [RCD 06-304-1, 09-012] FX This study was funded by the VA Health Services Research & Development (HSR&D) Rapid Response Project 11-019. The Center for Chronic Disease Outcomes Research is supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development and Health Services Research and Development. Dr. Zillich was supported by VA HSR&D Research Career Development Award (RCD 06-304-1). Dr. Widome was supported by a VA HSR&D Career Development Award #09-012. VA HSR&D had no role in the study design, data collection, analysis or interpretation, writing of the manuscript, and in the decision to submit the paper for publication. NR 27 TC 6 Z9 6 U1 1 U2 15 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD JAN PY 2015 VL 98 IS 1 BP 61 EP 68 DI 10.1016/j.pec.2014.10.007 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA AX5FO UT WOS:000346952400008 PM 25455795 ER PT J AU McMullen, CK Safford, MM Bosworth, HB Phansalkar, S Leong, A Fagan, MB Trontell, A Rumptz, M Vandermeer, ML Brinkman, WB Burkholder, R Frank, L Hommel, K Mathews, R Hornbrook, MC Seid, M Fordis, M Lambertt, B McElwee, N Singh, JA AF McMullen, Carmit K. Safford, Monika M. Bosworth, Hayden B. Phansalkar, Shobha Leong, Amye Fagan, Maureen B. Trontell, Anne Rumptz, Maureen Vandermeer, Meredith L. Brinkman, William B. Burkholder, Rebecca Frank, Lori Hommel, Kevin Mathews, Robin Hornbrook, Mark C. Seid, Michael Fordis, Michael Lambertt, Bruce McElwee, Newell Singh, Jasvinder A. CA CERTs PCMM Workshop Working Grp TI Patient-centered priorities for improving medication management and adherence SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Patient-centered research; Adherence; Chronic disease; Medication management; Stakeholder engagement ID OF-THE-LITERATURE; CARE; METAANALYSIS; INTERVENTIONS; STATEMENT; OUTCOMES; COST; RISK AB Objective: The Centers for Education and Research on Therapeutics convened a workshop to examine the scientific evidence on medication adherence interventions from the patient-centered perspective and to explore the potential of patient-centered medication management to improve chronic disease treatment. Methods: Patients, providers, researchers, and other stakeholders (N = 28) identified and prioritized ideas for future research and practice. We analyzed stakeholder voting on priorities and reviewed themes in workshop discussions. Results: Ten priority areas emerged. Three areas were highly rated by all stakeholder groups: creating tools and systems to facilitate and evaluate patient-centered medication management plans; developing training on patient-centered prescribing for providers; and increasing patients' knowledge about medication management. However, priorities differed across stakeholder groups. Notably, patients prioritized using peer support to improve medication management while researchers did not. Conclusion: Engaging multiple stakeholders in setting a patient-centered research agenda and broadening the scope of adherence interventions to include other aspects of medication management resulted in priorities outside the traditional scope of adherence research. Practice Implications: Workshop participants recognized the potential benefits of patient-centered medication management but also identified many challenges to implementation that require additional research and innovation. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [McMullen, Carmit K.; Rumptz, Maureen; Vandermeer, Meredith L.; Hornbrook, Mark C.] Kaiser Permanente Northwest, Ctr Hlth Res, Portland, OR 97227 USA. [Safford, Monika M.; Singh, Jasvinder A.] Univ Alabama Birmingham, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA. [Bosworth, Hayden B.; Mathews, Robin] Duke Univ, Durham, NC USA. [Phansalkar, Shobha] Partners Healthcare Syst Inc, Wellesley, MA USA. [Phansalkar, Shobha] Brigham & Womens Hosp, Boston, MA 02115 USA. [Phansalkar, Shobha; Fagan, Maureen B.] Harvard Univ, Sch Med, Boston, MA USA. [Leong, Amye] Healthy Motivat, Santa Barbara, CA USA. [Fagan, Maureen B.] Brigham & Womens Hosp, Ctr Patients & Families, Boston, MA 02115 USA. [Trontell, Anne] Agcy Hlth Care Res & Qual, Rockville, MD USA. [Brinkman, William B.; Hommel, Kevin; Seid, Michael] Cincinnati Childrens Hosp & Med Ctr, Cincinnati, OH USA. [Burkholder, Rebecca] Natl Consumers League, Washington, DC USA. [Frank, Lori] Patient Ctr Outcomes Res Inst, Washington, DC USA. [Fordis, Michael] Baylor Coll Med, Houston, TX 77030 USA. [Lambertt, Bruce] Northwestern Univ, Ctr Commun & Hlth, Chicago, IL 60611 USA. [McElwee, Newell] Merck & Co Inc, New York, NY USA. [Singh, Jasvinder A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP McMullen, CK (reprint author), Kaiser Permanente Northwest, Ctr Hlth Res, 3800N Interstate Ave, Portland, OR 97227 USA. EM Carmit.McMullen@kpchr.org FU Agency for Healthcare Research and Quality [U19HS021107] FX This project was supported by grant number U19HS021107 from the Agency for Healthcare Research and Quality. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality. We extend special acknowledgments to the late Jessie Gruman, who, as president and founder of the Center for Advancing Health provided a strong, articulate voice at the workshop. Her contributions as a patient representative brought focus and urgency to the issue of patient-centered medication management; she will be missed. NR 38 TC 4 Z9 4 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD JAN PY 2015 VL 98 IS 1 BP 102 EP 110 DI 10.1016/j.pec.2014.09.015 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA AX5FO UT WOS:000346952400014 PM 25448313 ER PT J AU Nguyen, KL Khan, SN Moriarty, JM Mohajer, K Renella, P Satou, G Ayad, I Patel, S Boechat, MI Finn, JP AF Nguyen, Kim-Lien Khan, Sarah N. Moriarty, John M. Mohajer, Kiyarash Renella, Pierangelo Satou, Gary Ayad, Ihab Patel, Swati Boechat, M. Ines Finn, J. Paul TI High-field MR imaging in pediatric congenital heart disease: Initial results SO PEDIATRIC RADIOLOGY LA English DT Article DE Magnetic resonance imaging; Magnetic resonance angiography; 3.0 Tesla; Congenital heart disease; Cardiovascular; Neonate; Children ID TO-NOISE RATIO; CARDIOVASCULAR MAGNETIC-RESONANCE; STATE FREE PRECESSION; CLINICAL-APPLICATIONS; TECHNICAL CONSIDERATIONS; SPATIAL-RESOLUTION; HIGH AGREEMENT; 3.0 TESLA; ANGIOGRAPHY; CHILDREN AB Comprehensive assessment of pediatric congenital heart disease (CHD) at any field strength mandates evaluation of both vascular and dynamic cardiac anatomy for which diagnostic quality contrast-enhanced magnetic resonance angiography (CEMRA) and cardiac cine are crucial. To determine whether high-resolution (HR) CEMRA and steady-state free precession (SSFP) cine can be performed reliably at 3.0 T in children with CHD and to compare the image quality to similar techniques performed at 1.5 T. Twenty-eight patients with a median age of 5 months and average weight 9.0 +/- 7.8 kg with suspected or known CHD were evaluated at 3.0 T. SSFP cine (n = 86 series) and HR-CEMRA (n = 414 named vascular segments) were performed and images were scored for image quality and artifacts. The findings were compared to those of 28 patients with CHD of similar weight who were evaluated at 1.5 T. Overall image quality on HR-CEMRA was rated as excellent or good in 96% (397/414) of vascular segments at 3.0 T (k = 0.49) and in 94% (349/371) of vascular segments at 1.5 T (k = 0.36). Overall image quality of SSFP was rated excellent or good in 91% (78/86) of cine series at 3.0 T (k = 0.55) and in 81% (87/108) at 1.5 T (k = 0.47). Off-resonance artifact was common at both field strengths, varied over the cardiac cycle and was more prevalent at 3.0 T. At 3.0 T, off-resonance dark band artifact on SSFP cine was absent in 3% (3/86), mild in 69% (59/86), moderate in 27% (23/86) and severe in 1% (1/86) of images; at 1.5 T, dark band artifact was absent in 16% (17/108), mild in 69% (75/108), moderate in 12% (13/108) and severe in 3% (3/108) of cine images. The signal-to-noise ratio and contrast-to-noise ratio of both SSFP cine and HR-CEMRA images were significantly higher at 3.0 T than at 1.5 T (P < 0.001). Signal-to-noise ratio and contrast-to-noise ratio of high-resolution contrast-enhanced magnetic resonance angiography and SSFP cine were higher at 3.0 T than at 1.5 T. Artifacts on SSFP cine were cardiac phase specific and more prevalent at 3.0 T such that frequency-tuning was required in one-third of exams. In neonates, high spatial resolution CEMRA was highly reliable in defining extracardiac vascular anatomy. C1 [Nguyen, Kim-Lien] Univ Calif Los Angeles, David Geffen Sch Med, Div Cardiol, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Khan, Sarah N.; Moriarty, John M.; Mohajer, Kiyarash; Renella, Pierangelo; Boechat, M. Ines; Finn, J. Paul] Univ Calif Los Angeles, Dept Radiol Sci, Los Angeles, CA 90095 USA. [Satou, Gary] Univ Calif Los Angeles, David Geffen Sch Med, Div Pediat Cardiol, Los Angeles, CA 90095 USA. [Ayad, Ihab; Patel, Swati] Univ Calif Los Angeles, David Geffen Sch Med, Dept Anesthesia, Los Angeles, CA 90095 USA. RP Finn, JP (reprint author), Univ Calif Los Angeles, Dept Radiol Sci, Peter V Ueberroth Bldg,Ste 3371,10945 Le Conte, Los Angeles, CA 90095 USA. EM pfinn@mednet.ucla.edu OI Nguyen, Kim-Lien/0000-0002-8854-2976 NR 42 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 EI 1432-1998 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD JAN PY 2015 VL 45 IS 1 BP 42 EP 54 DI 10.1007/s00247-014-3093-y PG 13 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA AX8NB UT WOS:000347165000009 PM 25086500 ER PT J AU Rogowski, W Payne, K Schnell-Inderst, P Manca, A Rochau, U Jahn, B Alagoz, O Leidl, R Siebert, U AF Rogowski, Wolf Payne, Katherine Schnell-Inderst, Petra Manca, Andrea Rochau, Ursula Jahn, Beate Alagoz, Oguzhan Leidl, Reiner Siebert, Uwe TI Concepts of 'Personalization' in Personalized Medicine: Implications for Economic Evaluation SO PHARMACOECONOMICS LA English DT Article ID DISCRETE-CHOICE EXPERIMENTS; ANALYSIS TASK-FORCE; COST-EFFECTIVENESS; HEALTH-CARE; INFORMATION ANALYSIS; COLORECTAL-CANCER; TECHNOLOGY; OUTCOMES; PREFERENCES; HETEROGENEITY AB This study assesses if, and how, existing methods for economic evaluation are applicable to the evaluation of personalized medicine (PM) and, if not, where extension to methods may be required. A structured workshop was held with a predefined group of experts (n = 47), and was run using a modified nominal group technique. Workshop findings were recorded using extensive note taking, and summarized using thematic data analysis. The workshop was complemented by structured literature searches. The key finding emerging from the workshop, using an economic perspective, was that two distinct, but linked, interpretations of the concept of PM exist (personalization by 'physiology' or 'preferences'). These interpretations involve specific challenges for the design and conduct of economic evaluations. Existing evaluative (extra-welfarist) frameworks were generally considered appropriate for evaluating PM. When 'personalization' is viewed as using physiological biomarkers, challenges include representing complex care pathways; representing spillover effects; meeting data requirements such as evidence on heterogeneity; and choosing appropriate time horizons for the value of further research in uncertainty analysis. When viewed as tailoring medicine to patient preferences, further work is needed regarding revealed preferences, e.g. treatment (non)adherence; stated preferences, e.g. risk interpretation and attitude; consideration of heterogeneity in preferences; and the appropriate framework (welfarism vs. extra-welfarism) to incorporate non-health benefits. Ideally, economic evaluations should take account of both interpretations of PM and consider physiology and preferences. It is important for decision makers to be cognizant of the issues involved with the economic evaluation of PM to appropriately interpret the evidence and target future research funding. C1 [Rogowski, Wolf; Leidl, Reiner] Helmholtz Zentrum Munchen, Inst Hlth Econ & Hlth Care Management, D-85764 Neuherberg, Germany. [Rogowski, Wolf] Univ Munich, Inst & Outpatient Clin Occupat Social & Environm, Munich, Germany. [Payne, Katherine] Univ Manchester, Inst Populat Hlth, Manchester Ctr Hlth Econ, Manchester, Lancs, England. [Schnell-Inderst, Petra; Rochau, Ursula; Jahn, Beate; Siebert, Uwe] UMIT Univ Hlth Sci Med Informat & Technol, Inst Publ Hlth Med Decis Making & Hlth Technol As, Dept Publ Hlth & Hlth Technol Assessment, Hall In Tirol, Austria. [Schnell-Inderst, Petra; Rochau, Ursula; Jahn, Beate; Siebert, Uwe] ONCOTYROL Ctr Personalized Canc Med, Div Hlth Technol Assessment & Bioinformat, Innsbruck, Austria. [Manca, Andrea] Univ York, Ctr Hlth Econ, York YO10 5DD, N Yorkshire, England. [Alagoz, Oguzhan] Univ Wisconsin, Dept Populat Hlth Sci, Dept Ind & Syst Engn, Madison, WI USA. [Leidl, Reiner] Univ Munich, Munich Ctr Hlth Sci, Munich, Germany. [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, Ctr Hlth Decis Sci, Boston, MA 02115 USA. RP Rogowski, W (reprint author), Univ Munich, Inst & Outpatient Clin Occupat Social & Environm, Munich, Germany. EM rogowski@helmholtz-muenchen.de RI Leidl, Reiner/B-7209-2009; OI Leidl, Reiner/0000-0002-7115-7510; Payne, Katherine/0000-0002-3938-4350 FU Uwe Siebert; Petra Schnell-Inderst, Beate Jahn; Ursula Rochau; COMET Center ONCOTYROL; Austrian Federal Ministries for Transport, Innovation and Technology, and for Economy, Family and Youth; Tiroler Zukunftsstiftung/Standortagentur Tirol (SAT); Individualized Health Care: Ethical, Economic and Legal Implications for the German Health Care System' of the German Federal Ministry of Education and Research (BMBF) [01GP1006B]; National Institute of Health Research (NIHR) [CDF-2009-02-21]; Oguzhan Alagoz [CMII-0844423]; National Science Foundation [UL1TR000427]; Clinical and Translational Science Award (CTSA) program; NIH National Center for Advancing Translational Sciences (NCATS) FX The workshop organization and funding, as well as the contribution by Uwe Siebert, Petra Schnell-Inderst, Beate Jahn, and Ursula Rochau, was supported by the COMET Center ONCOTYROL, which is funded by the Austrian Federal Ministries for Transport, Innovation and Technology, and for Economy, Family and Youth (via the Austrian Research Promotion Agency) and the Tiroler Zukunftsstiftung/Standortagentur Tirol (SAT).; The work of Wolf Rogowski in the preparation of this article was supported by the grant 'Individualized Health Care: Ethical, Economic and Legal Implications for the German Health Care System' of the German Federal Ministry of Education and Research (BMBF; grant number 01GP1006B).; The contribution from Andrea Manca was made under the terms of a career development research training fellowship issued by the National Institute of Health Research (NIHR; grant CDF-2009-02-21). Oguzhan Alagoz is funded by grant CMII-0844423 from the National Science Foundation, and grant UL1TR000427 from the Clinical and Translational Science Award (CTSA) program, through the NIH National Center for Advancing Translational Sciences (NCATS). All other authors have no relevant funding sources to declare. NR 62 TC 9 Z9 9 U1 3 U2 26 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 1170-7690 EI 1179-2027 J9 PHARMACOECONOMICS JI Pharmacoeconomics PD JAN PY 2015 VL 33 IS 1 BP 49 EP 59 DI 10.1007/s40273-014-0211-5 PG 11 WC Economics; Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Business & Economics; Health Care Sciences & Services; Pharmacology & Pharmacy GA AX8IG UT WOS:000347152700006 PM 25249200 ER PT J AU Belanger, AY Cameron, MH Michlovitz, SL Bellew, JW Freeman, L AF Belanger, Alain Yvan Cameron, Michelle H. Michlovitz, Susan L. Bellew, James W. Freeman, Lynn TI The American Physical Therapy Association's top five Choosing Wisely recommendations SO PHYSICAL THERAPY LA English DT Letter C1 [Belanger, Alain Yvan] Univ Laval, Fac Med, Rehabil Dept, Quebec City, PQ G1K 7P4, Canada. [Cameron, Michelle H.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Cameron, Michelle H.] Portland VA Med Ctr, Portland, OR USA. [Michlovitz, Susan L.] Cayuga Hand Therapy & PT, Ithaca, NY USA. [Michlovitz, Susan L.] Cayuga Hand Therapy & PT, Indianapolis, IN 46227 USA. [Bellew, James W.] Univ Indianapolis, Indianapolis, IN 46227 USA. RP Belanger, AY (reprint author), Univ Laval, Fac Med, Rehabil Dept, Quebec City, PQ G1K 7P4, Canada. EM alainybelanger@gmail.com NR 5 TC 3 Z9 3 U1 0 U2 1 PU AMER PHYSICAL THERAPY ASSOC PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 USA SN 0031-9023 EI 1538-6724 J9 PHYS THER JI Phys. Ther. PD JAN PY 2015 VL 95 IS 1 BP 142 EP 143 DI 10.2522/ptj.2015.95.1.142 PG 2 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA AX8FU UT WOS:000347146400014 PM 25554705 ER PT J AU Frederick, MJ Colwell, AS AF Frederick, Michael J. Colwell, Amy S. TI Acute Hypertensive Crisis Secondary to Pheochromocytoma during Elective Cosmetic Surgery SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Letter ID ANESTHESIA C1 [Frederick, Michael J.; Colwell, Amy S.] Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. RP Frederick, MJ (reprint author), MGH Plast Surg, 55 Fruit St, Boston, MA 02114 USA. EM mfrederick1@partners.org NR 5 TC 0 Z9 0 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JAN PY 2015 VL 135 IS 1 BP 238E EP 239E DI 10.1097/PRS.0000000000000784 PG 2 WC Surgery SC Surgery GA AX4OG UT WOS:000346911000040 PM 25539346 ER PT J AU Carbonaro, TM Eshleman, AJ Forster, MJ Cheng, KJ Rice, KC Gatch, MB AF Carbonaro, Theresa M. Eshleman, Amy J. Forster, Michael J. Cheng, Kejun Rice, Kenner C. Gatch, Michael B. TI The role of 5-HT2A, 5-HT2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice SO PSYCHOPHARMACOLOGY LA English DT Article DE N,N-diisopropyltryptamine; N,N-dimethyltryptamine; Hallucinogens; Drug discrimination; 5-HT2A; 5-HT2C; mGluR2; Rat ID DISCRIMINATIVE STIMULUS; DOSE-RESPONSE; DRUG DISCRIMINATION; BINDING; HUMANS; LSD; LOCALIZATION; AGONISTS AB Serotonin 5-HT2A and 5-HT2C receptors are thought to be the primary pharmacological mechanisms for serotonin-mediated hallucinogenic drugs, but recently there has been interest in metabotropic glutamate (mGluR2) receptors as contributors to the mechanism of hallucinogens. The present study assesses the role of these 5-HT and glutamate receptors as molecular targets for two tryptamine hallucinogens, N,N-dimethyltryptamine (DMT) and N,N-diisopropyltryptamine (DiPT). Drug discrimination, head twitch, and radioligand binding assays were used. A 5-HT2AR inverse agonist (MDL100907), 5-HT2CR antagonist (SB242084), and mGluR2/3 agonist (LY379268) were tested for their ability to attenuate the discriminative stimulus effects of DMT and DiPT; an mGluR2/3 antagonist (LY341495) was tested for potentiation. MDL100907 was used to attenuate head twitches induced by DMT and DiPT. Radioligand binding studies and inosital-1-phosphate (IP-1) accumulation were performed at the 5-HT2CR for DiPT. MDL100907 fully blocked the discriminative stimulus effects of DMT, but only partially blocked DiPT. SB242084 partially attenuated the discriminative stimulus effects of DiPT, but produced minimal attenuation of DMT's effects. LY379268 produced potent, but only partial blockade of the discriminative stimulus effects of DMT. LY341495 facilitated DMT- and DiPT-like effects. Both compounds elicited head twitches (DiPT > DMT) which were blocked by MDL1000907. DiPT was a low-potency full agonist at 5-HT2CR in vitro. The 5-HT2AR likely plays a major role in mediating the effects of both compounds. 5-HT2C and mGluR2 receptors likely modulate the discriminative stimulus effects of both compounds to some degree. C1 [Carbonaro, Theresa M.; Forster, Michael J.; Gatch, Michael B.] Univ North Texas Hlth Sci Ctr, Dept Pharmacol & Neurosci, Ft Worth, TX 76107 USA. [Eshleman, Amy J.] Portland VA Med Ctr, Res Serv, Portland, OR USA. [Eshleman, Amy J.] Oregon Hlth & Sci Univ, Dept Psychiat & Behav Neurosci, Portland, OR 97201 USA. [Cheng, Kejun; Rice, Kenner C.] NIDA, Chem Biol Res Branch, Bethesda, MD 20892 USA. [Cheng, Kejun; Rice, Kenner C.] NIAAA, Bethesda, MD 20892 USA. RP Gatch, MB (reprint author), Univ North Texas Hlth Sci Ctr, Dept Pharmacol & Neurosci, 3500 Camp Bowie Blvd, Ft Worth, TX 76107 USA. EM michael.gatch@unthsc.edu FU Addiction Treatment Discovery Program of the National Institute on Drug Abuse [NIH N01DA-7-8872]; National Institute on Drug Abuse; National Institute on Alcohol Abuse and Alcoholism; [T32 AG020494] FX Funding was provided by the Addiction Treatment Discovery Program of the National Institute on Drug Abuse (NIH N01DA-7-8872) and by T32 AG020494. A portion of this work was supported by the Intramural Research Programs of the National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism. There are no conflicts of interest. NR 33 TC 9 Z9 9 U1 5 U2 24 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JAN PY 2015 VL 232 IS 1 BP 275 EP 284 DI 10.1007/s00213-014-3658-3 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AX8NI UT WOS:000347165700023 PM 24985890 ER PT J AU Modjtahedi, BS Rong, A Bobinski, M McGahan, J Morse, LS AF Modjtahedi, Bobeck S. Rong, Andrew Bobinski, Mathew McGahan, John Morse, Lawrence S. TI IMAGING CHARACTERISTICS OF INTRAOCULAR FOREIGN BODIES A Comparative Study of Plain Film X-Ray, Computed Tomography, Ultrasound, and Magnetic Resonance Imaging SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE computed tomography; intraocular foreign body; magnetic resonance imaging; radiograph; retina; trauma; ultrasound; vitreous; x-ray ID IN-VITRO MODEL; CT; ORBIT; SIZE AB Purpose: To determine the imaging features of common intraocular foreign bodies (IOFBs) and the ability to differentiate types of IOFBs. Methods: Four-mm IOFBs were inserted via through pars plana approach into cadaveric lamb eyes. Six metallic (aluminum, brass, copper, silver, steel, and lead) and seven nonmetallic (plastic [CF6 spectacle plastic and polyvinyl chloride pipe], glass [bottle glass and windshield glass], wood [dry and wet poplar], and stone [slate]) IOFBs were imaged using plain film x-ray, computed tomography scan, ultrasound, and magnetic resonance imaging (T1, T2, and gradient echo sequences). Results: Plain film x-ray had limited ability to differentiate most IOFBs. Computed tomography findings can be divided into low attenuation objects (wood), moderate attenuation (CF6 spectacle plastic), high attenuation without surrounding artifact (polyvinyl chloride, slate, bottle glass, windshield glass, and aluminum), high attenuation with shadow artifact and minimal edge streak artifact (steel, brass, copper), and high attenuation with significant shadow artifact and prominent streak artifact (silver and lead). Density (in Hounsfield units) aided in differentiating the types of IOFBs. Gradient echo sequences on magnetic resonance imaging also held utility. Ultrasound images had considerable overlap in appearances. Conclusion: Imaging techniques can significantly aid in determining the IOFBs type, with computed tomography serving as the best initial modality. X-ray holds limited utility while ultrasound and magnetic resonance imaging are best reserved as adjunctive tests. C1 [Modjtahedi, Bobeck S.; Rong, Andrew; Morse, Lawrence S.] Univ Calif Davis, Dept Ophthalmol & Vis Sci, Sacramento, CA 95817 USA. [Modjtahedi, Bobeck S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Bobinski, Mathew; McGahan, John] Univ Calif Davis, Dept Radiol, Sacramento, CA 95817 USA. RP Modjtahedi, BS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM Bobeck_Modjtahedi@MEEI.Harvard.Edu OI Morse, Lawrence/0000-0002-1758-2348 FU Research to Prevent Blindness; Heed Ophthalmic Foundation FX Supported by an unrestricted grant from Research to Prevent Blindness. B. S. Modjtahedi receives research support from the Heed Ophthalmic Foundation. NR 11 TC 3 Z9 3 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0275-004X EI 1539-2864 J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD JAN PY 2015 VL 35 IS 1 BP 95 EP 104 PG 10 WC Ophthalmology SC Ophthalmology GA AX6WX UT WOS:000347060000021 PM 25090044 ER PT J AU Lupon, J Januzzi, JL de Antonio, M Vila, J Penafilel, J Bayes-Genis, A AF Lupon, Josep Januzzi, James L. de Antonio, Marta Vila, Joan Penafilel, Judith Bayes-Genis, Antoni TI Validation of the Barcelona Bio-Heart Failure Risk Calculator in a Cohort From Boston SO REVISTA ESPANOLA DE CARDIOLOGIA LA English DT Letter ID SURVIVAL; CARDIOLOGY C1 [Lupon, Josep; de Antonio, Marta; Bayes-Genis, Antoni] Hosp Badalona Germans Trias & Pujol, Unitat Insuficiencia Cardiaca, Badalona, Spain. [Lupon, Josep; de Antonio, Marta; Bayes-Genis, Antoni] Univ Autonoma Barcelona, Dept Med, E-08193 Barcelona, Spain. [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Vila, Joan; Penafilel, Judith] Hosp del Mar, Inst Recerca Med, Barcelona, Spain. RP Lupon, J (reprint author), Hosp Badalona Germans Trias & Pujol, Unitat Insuficiencia Cardiaca, Badalona, Spain. EM jlupon.germanstrias@gencat.cat RI Bayes-Genis, Antoni/C-4002-2015; OI Bayes-Genis, Antoni/0000-0002-3044-197X; Lupon, Josep/0000-0002-3981-3020; Lupon, Josep/0000-0002-5601-9611 NR 9 TC 1 Z9 1 U1 0 U2 3 PU EDICIONES DOYMA S A PI BARCELONA PA TRAV DE GRACIA 17-21, 08021 BARCELONA, SPAIN SN 0300-8932 EI 1579-2242 J9 REV ESP CARDIOL JI Rev. Esp. Cardiol. PD JAN PY 2015 VL 68 IS 1 BP 80 EP 81 DI 10.1016/j.rec.2014.08.009 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AX6LI UT WOS:000347033400017 PM 25440177 ER PT J AU Kubicki, M Shenton, ME AF Kubicki, Marek Shenton, Martha E. TI Editorial to Special Issue on "White Matter Pathology" SO SCHIZOPHRENIA RESEARCH LA English DT Editorial Material ID MAGNETIC-RESONANCE; SCHIZOPHRENIA C1 [Kubicki, Marek; Shenton, Martha E.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Kubicki, Marek; Shenton, Martha E.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Kubicki, Marek; Shenton, Martha E.] Harvard Univ, Sch Med, Boston, MA USA. [Kubicki, Marek; Shenton, Martha E.] Brigham & Womens Hosp, Psychiat Neuroimaging Lab, Boston, MA 02115 USA. [Kubicki, Marek] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shenton, Martha E.] VA Boston Healthcare Syst, Boston, MA USA. RP Kubicki, M (reprint author), Brigham & Womens Hosp, Dept Psychiat, 75 Francis St, Boston, MA 02115 USA. FU PHS HHS [R01 M074794] NR 6 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 2015 VL 161 IS 1 BP 1 EP 3 DI 10.1016/j.schres.2014.12.015 PG 3 WC Psychiatry SC Psychiatry GA AX1WG UT WOS:000346733400001 PM 25541300 ER PT J AU Kates, WR Olszewski, AK Gnirke, M Kikinis, Z Nelson, J Antshel, KM Fremont, W Radoeva, PD Middleton, FA Shenton, ME Coman, IL AF Kates, Wendy R. Olszewski, Amy K. Gnirke, MatthewH. Kikinis, Zora Nelson, Joshua Antshel, Kevin M. Fremont, Wanda Radoeva, Petya D. Middleton, Frank A. Shenton, Martha E. Coman, Ioana L. TI White matter microstructural abnormalities of the cingulum bundle in youths with 22q11.2 deletion syndrome: Associations with medication, neuropsychological function, and prodromal symptoms of psychosis SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Velo-cardio-facial syndrome; Diffusion tensor imaging (DTI); Cingulum bundle; Prodromal symptoms of psychosis; Schizophrenia; Antipsychotics/mood stabilizers ID CARDIO-FACIAL SYNDROME; ULTRA-HIGH-RISK; VELOCARDIOFACIAL SYNDROME; ANTIPSYCHOTIC TREATMENT; CHROMOSOME 22Q11.2; AXIAL DIFFUSIVITY; ATYPICAL ANTIPSYCHOTICS; RADIAL DIFFUSIVITY; LONGITUDINAL MRI; CORPUS-CALLOSUM AB Background: The 22q11.2 deletion syndrome (22q11.2DS) is regarded as an etiologically homogenous model for understanding neuroanatomic disruptions associated with a high risk for schizophrenia. This study utilized diffusion tensor imaging (DTI) to analyze white matter microstructure in individuals with 22q11.2DS. We focused on the cingulum bundle (CB), previously shown to be disrupted in patients with schizophrenia and associated with symptoms of psychosis. Methods: White matter microstructure was assessed in the anterior, superior, and posterior CB using the tractography algorithm in DTIStudio. Neuropsychological function, presence of prodromal symptoms of psychosis, and medication history were assessed in all participants. Results: Relative to controls, young adults with 22q11.2DS showed alterations in most DTI metrics of the CB. Alterations were associated with positive prodromal symptoms of psychosis. However, when individuals with 22q11.2DS were divided by usage of antipsychotics/mood stabilizers, the medicated and non-medicated groups differed significantly in axial diffusivity of the anterior CB and in fractional anisotropy of the superior CB. DTI metrics did not differ between the medicated group and the control group. Conclusions: Results suggest that the microstructure of the CB is altered in individuals with 22q11.2DS, and that those alterations may underlie positive prodromal symptoms of psychosis. Our findings further provide preliminary evidence that antipsychotic/mood stabilizer usage may have a reparative effect on white matter microstructure in prodromal 22q11.2DS, independent of the potential effects of psychosis. Future studies of white matter pathology in individuals with 22q11.2DS should test for potential effects of medication on white matter microstructure. (C) 2014 Elsevier B.V. All rights reserved. C1 [Kates, Wendy R.; Olszewski, Amy K.; Gnirke, MatthewH.; Nelson, Joshua; Antshel, Kevin M.; Fremont, Wanda; Radoeva, Petya D.; Middleton, Frank A.; Coman, Ioana L.] SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY 13210 USA. [Middleton, Frank A.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA. [Antshel, Kevin M.] Syracuse Univ, Dept Psychol, Syracuse, NY USA. [Kikinis, Zora; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Shenton, Martha E.] VA Boston Healthcare Syst, Brockton Div, Brockton, MA USA. RP Kates, WR (reprint author), SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, 750 East Adams St, Syracuse, NY 13210 USA. EM katesw@upstate.edu OI kikinis, zora/0000-0002-7203-1362 FU National Institutes of Health [MH064824] FX This work was supported by funding from the National Institutes of Health (MH064824) to WRK. NR 96 TC 11 Z9 11 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 2015 VL 161 IS 1 BP 76 EP 84 DI 10.1016/j.schres.2014.07.010 PG 9 WC Psychiatry SC Psychiatry GA AX1WG UT WOS:000346733400010 PM 25066496 ER PT J AU Mandl, RCW Pasternak, O Cahn, W Kubicki, M Kahn, RS Shenton, ME Pol, HEH AF Mandl, Rene C. W. Pasternak, Ofer Cahn, Wiepke Kubicki, Marek Kahn, Rene S. Shenton, Martha E. Pol, Hilleke E. Hulshoff TI Comparing free water imaging and magnetization transfer measurements in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Fiber based analysis; MTR; Free water imaging; Human brain; White matter; Schizophrenia ID WHITE-MATTER ABNORMALITIES; AUDITORY VERBAL HALLUCINATIONS; RECENT-ONSET SCHIZOPHRENIA; DIFFUSION-TENSOR MRI; LIVING HUMAN BRAIN; IN-VIVO; ARCUATE FASCICULUS; MTR ABNORMALITIES; CONNECTIVITY; 1ST-EPISODE AB Diffusion weighted imaging (DWI) has been extensively used to study the microarchitecture of white matter in schizophrenia. However, popular DWI-derived measures such as fractional anisotropy (FA) may be sensitive to many types of pathologies, and thus the interpretation of reported differences in these measures remains difficult. Combining DWI with magnetization transfer ratio (MTR) - a putative measure of white matter myelination - can help us reveal the underlying mechanisms. Previous findings hypothesized that MTR differences in schizophrenia are associated with free water concentrations, which also affect the DWIs. In this study we use a recently proposed DWI-derived method called free-water imaging to assess this hypothesis. We have reanalyzed data from a previous study by using a fiber-based analysis of free-water imaging, providing a free-water fraction, as well as mean diffusivity and FA corrected for free-water, in addition to MTR along twelve major white matter fiber bundles in 40 schizophrenia patients and 40 healthy controls. We tested for group differences in each fiber bundle and for each measure separately and computed correlations between the MTR and the DWI-derived measures separately for both groups. Significant higher average MTR values in patients were found for the right uncinate fasciculus, the right arcuate fasciculus and the right inferior-frontal occipital fasciculus. No significant results were found for the other measures. No significant differences in correlations were found between MTR and the DWI-derived measures. The results suggest that MTR and free-water imaging measures can be considered complementary, promoting the acquisition of MTR in addition to DWI to identify group differences, as well as to better understand the underlying mechanisms in schizophrenia. (C) 2014 Elsevier B.V. All rights reserved. C1 [Mandl, Rene C. W.; Cahn, Wiepke; Kahn, Rene S.; Pol, Hilleke E. Hulshoff] Univ Med Ctr Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, Utrecht, Netherlands. [Pasternak, Ofer; Kubicki, Marek; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Pasternak, Ofer; Kubicki, Marek; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Shenton, Martha E.] VA Boston Healthcare Syst, Brockton, MA USA. RP Mandl, RCW (reprint author), Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Psychiat, A01-126,Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands. EM r.mandl@umcutrecht.nl FU NIH [P41RR013218, P41EB015902, R01MH074794]; NARSAD (National Alliance for Research on Schizophrenia and Depression) Young Investigator grant from the Brain & Behavior Research Foundation FX This work was partially funded by grants from the NIH (nos. P41RR013218, P41EB015902, and R01MH074794). OP was partially supported by a NARSAD (National Alliance for Research on Schizophrenia and Depression) Young Investigator grant from the Brain & Behavior Research Foundation. NR 67 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 2015 VL 161 IS 1 BP 126 EP 132 DI 10.1016/j.schres.2014.09.046 PG 7 WC Psychiatry SC Psychiatry GA AX1WG UT WOS:000346733400016 PM 25454797 ER PT J AU Ensrud, KE Guthrie, KA Hohensee, C Caan, B Carpenter, JS Freeman, EW LaCroix, AZ Landis, CA Manson, J Newton, KM Otte, J Reed, SD Shifren, JL Sternfeld, B Woods, NF Joffe, H AF Ensrud, Kristine E. Guthrie, Katherine A. Hohensee, Chancellor Caan, Bette Carpenter, Janet S. Freeman, Ellen W. LaCroix, Andrea Z. Landis, Carol A. Manson, JoAnn Newton, Katherine M. Otte, Julie Reed, Susan D. Shifren, Jan L. Sternfeld, Barbara Woods, Nancy F. Joffe, Hadine TI Effects of Estradiol and Venlafaxine on Insomnia Symptoms and Sleep Quality in Women with Hot Flashes SO SLEEP LA English DT Article DE randomized trial; estradiol; venlafaxine; sleep; hot flashes; menopause ID RANDOMIZED CONTROLLED-TRIAL; MENOPAUSAL VASOMOTOR SYMPTOMS; ESTROGEN PLUS PROGESTIN; LOW-DOSE ESTRADIOL; POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; SEVERITY INDEX; CLINICAL-TRIAL; BREAST-CANCER; DOUBLE-BLIND AB Study Objectives: Determine effects of low-dose estradiol and low-dose venlafaxine on self-reported sleep measures in menopausal women with hot flashes. Design: 3-arm double-blind randomized trial. Participants assigned in a 2: 2: 3 ratio to 17 beta estradiol 0.5 mg/day (n = 97), venlafaxine XR 75 mg/day (n = 96), or placebo (n = 146) for 8 weeks. Setting: Academic research centers. Participants: 339 community-dwelling perimenopausal and postmenopausal women with = 2 bothersome hot flashes per day. Measurements and Results: Insomnia symptoms (Insomnia Severity Index [ISI]) and sleep quality (Pittsburgh Sleep Quality Index [PSQI]) at baseline, week 4 and 8; 325 women (96%) provided ISI data and 312 women (92%) provided PSQI data at baseline and follow-up. At baseline, mean (SD) hot flash frequency was 8.1/day (5.3), mean ISI was 11.1 (6.0), and mean PSQI was 7.5 (3.4). Mean (95% CI) change from baseline in ISI at week 8 was -4.1 points (-5.3 to -3.0) with estradiol, -5.0 points (-6.1 to -3.9) with venlafaxine, and -3.0 points (-3.8 to -2.3) with placebo (P overall treatment effect vs. placebo 0.09 for estradiol and 0.007 for venlafaxine). Mean (95% CI) change from baseline in PSQI at week 8 was -2.2 points (-2.8 to -1.6) with estradiol, -2.3 points (-2.9 to -1.6) with venlafaxine, and -1.2 points (-1.7 to -0.8) with placebo (P overall treatment effect vs. placebo 0.04 for estradiol and 0.06 for venlafaxine). Conclusions: Among perimenopausal and postmenopausal women with hot flashes, both low dose oral estradiol and low-dose venlafaxine compared with placebo modestly reduced insomnia symptoms and improved subjective sleep quality. C1 [Ensrud, Kristine E.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Ensrud, Kristine E.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Ensrud, Kristine E.] Minneapolis VA Hlth Care Syst, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Guthrie, Katherine A.; Hohensee, Chancellor; LaCroix, Andrea Z.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Caan, Bette; Sternfeld, Barbara] Kaiser Permanente, Div Res, Oakland, CA USA. [Carpenter, Janet S.; Otte, Julie] Indiana Univ, Sch Nursing, Indianapolis, IN 46204 USA. [Freeman, Ellen W.] Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Freeman, Ellen W.] Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA. [Landis, Carol A.; Woods, Nancy F.] Univ Washington, Dept Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA. [Manson, JoAnn] Harvard Univ, Brigham & Womens Hosp, Dept Med, Sch Med, Boston, MA 02115 USA. [Newton, Katherine M.] Grp Hlth Res Inst, Seattle, WA USA. [Reed, Susan D.] Univ Washington, Dept Med, Seattle, WA USA. [Shifren, Jan L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. [Joffe, Hadine] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Joffe, Hadine] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ensrud, KE (reprint author), One Vet Dr, Minneapolis, MN 55417 USA. EM ensru001@umn.edu FU National Institute of Aging (NIA); Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD); National Center for Complementary and Alternative Medicine (NCCAM); Office of Research on Women's Health (ORWH) [U01 AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, U01AG032700]; Cephalon/Teva FX This was not an industry supported study. The study was supported by a cooperative agreement issued by the National Institute of Aging (NIA), in collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD), the National Center for Complementary and Alternative Medicine (NCCAM), and the Office of Research on Women's Health (ORWH): # U01 AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, U01AG032700. Dr. Ensrud serves as a consultant on a Data Monitoring Committee for Merck Sharpe & Dohme. Dr. Otte reports consultant activities and honoraria from On Q Health, Inc. Dr. Shifren reports consultant activities for New England Research Institutes. Dr. Joffe reports research support from Cephalon/Teva; and consultant activities for Noven and Sunovion. The authors have indicated no financial conflicts of interest. NR 48 TC 7 Z9 7 U1 1 U2 2 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD JAN 1 PY 2015 VL 38 IS 1 BP 97 EP 108 DI 10.5665/sleep.4332 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AX8OT UT WOS:000347169300012 PM 25325454 ER PT J AU Fung, SJ Chase, MH AF Fung, Simon J. Chase, Michael H. TI Postsynaptic Inhibition of Hypoglossal Motoneurons Produces Atonia of the Genioglossal Muscle During Rapid Eye Movement Sleep SO SLEEP LA English DT Article DE atonia; hypoglossal; IPSP; motoneuron; OSA; postsynaptic inhibition; REM sleep ID ACTIVE SLEEP; MOTO-NEURONS; REM-SLEEP; RESPIRATORY MOTONEURONS; INTRACELLULAR ANALYSIS; NERVE-STIMULATION; XII-MOTONEURONS; SPINAL-CORD; CAT; RAT AB Study Objectives: Hypoglossal motoneurons were recorded intracellularly to determine whether postsynaptic inhibition or disfacilitation was responsible for atonia of the lingual muscles during rapid eye movement (REM) sleep. Design: Intracellular records were obtained of the action potentials and subthreshold membrane potential activity of antidromically identified hypoglossal motoneurons in cats during wakefulness, nonrapid eye movement (NREM) sleep, and REM sleep. A cuff electrode was placed around the hypoglossal nerve to antidromically activate hypoglossal motoneurons. The state-dependent changes in membrane potential, spontaneous discharge, postsynaptic potentials, and rheobase of hypoglossal motoneurons were determined. Analyses and Results: During quiet wakefulness and NREM sleep, hypoglossal motoneurons exhibited spontaneous repetitive discharge. In the transition from NREM sleep to REM sleep, repetitive discharge ceased and the membrane potential began to hyperpolarize; maximal hyperpolarization (10.5 mV) persisted throughout REM sleep. During REM sleep there was a significant increase in rheobase, which was accompanied by barrages of large-amplitude inhibitory postsynaptic potentials (IPSPs), which were reversed following the intracellular injection of chloride ions. The latter result indicates that they were mediated by glycine; IPSPs were not present during wakefulness or NREM sleep. Conclusions: We conclude that hypoglossal motoneurons are postsynaptically inhibited during naturally occurring REM sleep; no evidence of disfacilitation was observed. The data also indicate that glycine receptor-mediated postsynaptic inhibition of hypoglossal motoneurons is crucial in promoting atonia of the lingual muscles during REM sleep. C1 [Fung, Simon J.; Chase, Michael H.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Fung, Simon J.; Chase, Michael H.] WebSci Int, Los Angeles, CA 90024 USA. [Chase, Michael H.] Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90024 USA. RP Fung, SJ (reprint author), WebSci Int, 1251 Westwood Blvd, Los Angeles, CA 90024 USA. EM sfung@websciences.org FU [101BX00819]; [TGS-109219]; [1R01HL116845] FX This was not an industry supported study. This study was supported by grants 101BX00819, TGS-109219 and 1R01HL116845. The authors have indicated no financial conflicts of interest. NR 60 TC 5 Z9 5 U1 0 U2 2 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD JAN 1 PY 2015 VL 38 IS 1 BP 139 EP 146 DI 10.5665/sleep.4340 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AX8OT UT WOS:000347169300016 PM 25325470 ER PT J AU Dadras, SS Lin, RJ Razavi, G Kawakami, A Du, JY Feige, E Milner, DA Loda, MF Granter, SR Detmar, M Widlund, HR Horstmann, MA Fisher, DE AF Dadras, Soheil S. Lin, Richard J. Razavi, Gita Kawakami, Akinori Du, Jinyan Feige, Erez Milner, Daniel A. Loda, Massimo F. Granter, Scott R. Detmar, Michael Widlund, Hans R. Horstmann, Martin A. Fisher, David E. TI A Novel Role for Microphthalmia-Associated Transcription Factor-Regulated Pigment Epithelium-Derived Factor during Melanoma Progression SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID HUMAN-MALIGNANT MELANOMA; SENTINEL LYMPH-NODES; CUTANEOUS MELANOMA; TUMOR LYMPHANGIOGENESIS; LINEAGE SURVIVAL; HUMAN CANCER; METASTASIS; ANGIOGENESIS; GROWTH; MITF AB Microphthalmia-associated transcription factor (MITF) acts via pigment epithelium-derived factor (PEDF), an antiangiogenic protein, to regulate retinal pigment epithelium migration. PEDF expression and/or regulation during melanoma development have not been investigated previously. Using immunohistochemistry, we determined expression of PEDF in common and dysplastic melanocytic nevi, melanoma in situ, invasive melanoma, and metastatic melanoma (n = 102). PEDF expression was consistently decreased in invasive and metastatic melanoma, compared with nevi and melanoma in situ (P < 0.0001). PEDF was lost in thicker melanomas (P = 0.003), and correlated with depth of invasion (P = 0.003) and distant metastasis (P = 0.0331), but only marginally with mitotic index, AJCC stage, nodal metastasis, or blood vascular density (0.05 < P < 0.10). Quantitative real-time PCR and microarray analyses confirmed PEDF down-regulation at the mRNA level in several melanoma lines, compared with melanocytes. MITE positively correlated with PEDF expression in invasive melanomas (P = 0.0003). Searching for PEDF regulatory mechanisms revealed two occupied conserved E-boxes (DNA recognition elements) in the first intron of the human and mouse PEDF promoter regions, confirmed by binding assays. Dominant-negative and siRNA approaches in vivo demonstrated direct transcriptional influence of MITE on PEDF, establishing the PEDF gene (SERPINF1) as a MITF target in melanocytes and melanoma cells. These findings suggest that loss of PEDF expression promotes early invasive melanoma growth. C1 [Dadras, Soheil S.; Kawakami, Akinori; Detmar, Michael; Fisher, David E.] Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Dadras, Soheil S.; Kawakami, Akinori; Detmar, Michael; Fisher, David E.] Harvard Univ, Sch Med, Dept Dermatol, Charlestown, MA USA. [Lin, Richard J.; Feige, Erez; Milner, Daniel A.; Widlund, Hans R.; Fisher, David E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. [Lin, Richard J.; Feige, Erez; Milner, Daniel A.; Widlund, Hans R.; Fisher, David E.] Melanoma Program Med Oncol, Dept Pediat Hematol Oncol, Boston, MA USA. [Razavi, Gita] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. [Du, Jinyan] Merrimack Pharmaceut, Cambridge, MA USA. [Loda, Massimo F.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Granter, Scott R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Horstmann, Martin A.] Univ Med Ctr Hamburg Eppendoif, Res Inst, Hamburg, Germany. [Horstmann, Martin A.] Univ Med Ctr Hamburg Eppendoif, Clin Pediat Hematol & Oncol, Hamburg, Germany. RP Dadras, SS (reprint author), Univ Connecticut, Dept Dermatol, 21 South Rd, Farmington, CT 06030 USA. EM dadras@uchc.edu FU NIH [1-P01-CA163222, R01-AR043369-17]; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; American Cancer Society New England Division FX Supported by NIH grants 1-P01-CA163222 and R01-AR043369-17 (D.E.F.), the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (D.E.F.), and the American Cancer Society New England Division (R.J.L.). NR 47 TC 4 Z9 4 U1 3 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 2015 VL 185 IS 1 BP 252 EP 265 DI 10.1016/j.ajpath.2014.09.012 PG 14 WC Pathology SC Pathology GA AX4ES UT WOS:000346887200022 PM 25447045 ER PT J AU Shahid, M Mubeen, A Tse, J Kakar, S Bateman, AC Borger, D Rivera, MN Ting, DT Deshpande, V AF Shahid, Mohammad Mubeen, Aysha Tse, Julie Kakar, Sanjay Bateman, Adrian C. Borger, Darrell Rivera, Miguel N. Ting, David T. Deshpande, Vikram TI Branched Chain In Situ Hybridization for Albumin as a Marker of Hepatocellular Differentiation Evaluation of Manual and Automated In Situ Hybridization Platforms SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE in situ hybridization; albumin; hepatocellular carcinoma ID MESSENGER-RNA DETECTION; ALPHA-FETOPROTEIN; NORMAL LIVER; HEP PAR-1; CARCINOMA; ARGINASE-1; TUMORS; NEOPLASMS; HEPPAR-1; CHOLANGIOCARCINOMA AB Albumin, widely recognized as a highly sensitive and specific marker of hepatocellular carcinoma (HCC), is currently unavailable in the diagnostic laboratory because of the lack of a robust platform. In a prior study we detected albumin mRNA in the majority of intrahepatic cholangiocarcinomas using a novel branched chain RNA in situ hybridization (ISH) platform. We now explore the utility of albumin ISH as a marker of hepatocellular differentiation in HCCs, and compare its sensitivity with Hep Par 1 and Arginase-1. We evaluated 93 HCCs and its mimics including neuroendocrine tumors of the gastrointestinal tract (n=31), neuroendocrine tumors of the pancreas (n=163), melanoma (n=15), and gallbladder carcinoma (n=34). We performed ISH for albumin and immunohistochemistry for Hep Par 1 and Arginase-1. Five previously uncharacterized hepatic neoplasms from our files were also evaluated. Immunohistochemistry for Arginase-1 was performed on 59 intrahepatic cholangiocarcinomas. In addition, 43 HCCs evaluated on the manual platform were also examined on the automated instrument. Fifty-five percent of HCCs were moderately differentiated and 39% poorly differentiated. The sensitivity of ISH for albumin was 99%, with 92 of 93 HCCs staining positive for albumin. In contrast to ISH, the sensitivity of immunohistochemistry for Hep Par 1 and Arginase-1 was 84% and 83%, respectively. The sensitivity of albumin for poorly differentiated HCCs was 99%, whereas that for Arginase-1 and Hep Par 1 was 71% and 64%, respectively. Ninety-seven percent of the HCCs showed albumin positivity in >50% of tumor cells using the ISH platform, as compared with 76% and 70% for Hep Par 1 and Arginase-1 immunohistochemistry, respectively. Three of the 5 previously uncharacterized neoplasms were positive for albumin ISH. Automated albumin ISH platform performed equivalently to the manual format, with albumin reactivity in >50% of tumor cells in all 43 cases that were tested on both platforms. All non-HCCs were negative for albumin. All 59 intrahepatic cholangiocarcinomas were negative for Arginase-1. In conclusion, branched chain ISH performed on manual and automated mode is a robust assay for detecting albumin with sensitivity for poorly differentiated HCCs superior to Arginase-1 and Hep Par 1. When interpreted in conjunction with Arginase-1, albumin ISH offers a high level of sensitivity and specificity. C1 [Shahid, Mohammad; Mubeen, Aysha] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Tse, Julie; Borger, Darrell; Rivera, Miguel N.; Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ting, David T.] Massachusetts Gen Hosp, Dept Med, Div Oncol, Boston, MA 02114 USA. [Ting, David T.] Harvard Univ, Sch Med, Boston, MA USA. [Kakar, Sanjay] UCSF, San Francisco, CA USA. [Kakar, Sanjay] VA Med Ctr, San Francisco, CA USA. [Bateman, Adrian C.] Univ Hosp Southampton NHS Fdn Trust, Dept Cellular Pathol, Southampton, Hants, England. RP Deshpande, V (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2,55 Fruit St, Boston, MA 02114 USA. EM vikramdirdeshpande@gmail.com OI Ting, David/0000-0002-3261-2322 FU Howard Hughes Medical Institute; Burroughs Wellcome Trust; Affymetrix Inc.; [K12CA087723-11A1] FX Conflicts of Interest and Source of Funding: Supported by Howard Hughes Medical Institute (M.N.R.), the Burroughs Wellcome Trust (D.T.T., M.N.R.), K12CA087723-11A1 (D.T.T.), and Affymetrix Inc. (D.T.T., M.N.R., V.D.). The authors have disclosed that they have no significant financial interest in, any commercial companies pertaining to this article. NR 24 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 2015 VL 39 IS 1 BP 25 EP 34 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA AX2JE UT WOS:000346768600003 PM 25353287 ER PT J AU Agarwala, AV Firth, PG Albrecht, MA Warren, L Musch, G AF Agarwala, Aalok V. Firth, Paul G. Albrecht, Meredith A. Warren, Lisa Musch, Guido TI An Electronic Checklist Improves Transfer and Retention of Critical Information at Intraoperative Handoff of Care SO ANESTHESIA AND ANALGESIA LA English DT Article ID NEUROMUSCULAR BLOCKING-AGENTS; SIGN-OUT; PATIENT; COMMUNICATION; HANDOVERS; SURGERY; QUALITY; SAFETY; RISK AB BACKGROUND: Communication failures are a significant cause of preventable medical errors, and poor-quality handoffs are associated with adverse events. We developed and implemented a simple checklist to improve communication during intraoperative transfer of patient care. METHODS: A prospective observational assessment was performed to compare relay and retention of critical patient information between the outgoing and incoming anesthesiologist before and after introduction of an electronic handoff checklist. Secondary measurements included checklist usage and clinician satisfaction. RESULTS: Sixty-nine handoffs were observed (39 with and 30 without the checklist). Significant improvements in the frequency of information relay occurred with checklist use, most notably related to administration of vasopressors and antiemetics (85% vs 44%, P = 0.008; 46% vs 15%, P = 0.015, respectively); estimated blood loss and urine output (85% vs 57%, P = 0.014; 85% vs 52%, P = 0.006, respectively); communication about potential areas of concern (92% vs 57%, P = 0.001), postoperative planning (92% vs 43%, P < 0.001), and introduction of the relieving anesthesiologist to the operating team (51% vs 3%, P < 0.001). When queried after the handoff, relieving anesthesiologists more frequently knew the antibiotic (97% vs 75%, P = 0.020), muscle relaxant (97% vs 63%, P = 0.003), and amount of fluid administered (97% vs 72%, P = 0.008) when the checklist was used. Voluntary use of the checklist occurred in 60% of the handoffs by the end of the observation period (99% control limits: 58%-75%.). Clinicians who reported using the checklist in at least two-thirds of their handoffs reported higher satisfaction with quality of communication at handoff (P = 0.003). CONCLUSIONS: An electronic checklist improved relay and retention of critical patient information and clinician communication at intraoperative handoff of care. C1 [Musch, Guido] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Musch, G (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, GRJ 4-418,55 Fruit St, Boston, MA 02114 USA. EM gmusch@partners.org FU Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts FX Supported by the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts. NR 31 TC 4 Z9 4 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 EI 1526-7598 J9 ANESTH ANALG JI Anesth. Analg. PD JAN PY 2015 VL 120 IS 1 BP 96 EP 104 DI 10.1213/ANE.0000000000000506 PG 9 WC Anesthesiology SC Anesthesiology GA AW9TW UT WOS:000346601300017 PM 25625256 ER PT J AU Nutescu, EA Wittkowsky, AK Witt, DM Kaatz, S Ansell, J Burnett, A Garcia, D Lopes, RD Oertel, L Schnurr, T Streiff, M Wirth, D Crowther, M AF Nutescu, Edith A. Wittkowsky, Ann K. Witt, Daniel M. Kaatz, Scott Ansell, Jack Burnett, Allison Garcia, David Lopes, Renato D. Oertel, Lynn Schnurr, Terri Streiff, Michael Wirth, Diane Crowther, Mark TI Integrating Electronic Health Records in the Delivery of Optimized Anticoagulation Therapy SO ANNALS OF PHARMACOTHERAPY LA English DT Article ID CONSENSUS STATEMENT; FORUM AB Integration of accepted practice standards into electronic health record systems can facilitate standardization of anticoagulation care delivery and result in improved anticoagulation safety. However, the majority of commonly used electronic health record systems are lacking the specialized features necessary for optimal anticoagulation management. The Task Force on Electronic Health Records of the New York State Anticoagulation Coalition provides such a Consensus Statement in this issue of the journal. The Anticoagulation Forum endorses these recommendations and advises the electronic health record industry and health information technology programmers at the institutional level to adopt these recommendations in a comprehensive and timely manner. C1 [Nutescu, Edith A.] Univ Illinois, Chicago, IL 60612 USA. [Nutescu, Edith A.] Univ Illinois Hosp & Hlth Sci Syst, Chicago, IL USA. [Wittkowsky, Ann K.] Univ Washington Med Ctr, Seattle, WA USA. [Witt, Daniel M.] Kaiser Permanente, Aurora, CO USA. [Kaatz, Scott] Hurley Med Ctr, Flint Township, MI USA. [Ansell, Jack] Hofstra North Shore LIJ Sch Med, Hempstead, NY USA. [Burnett, Allison] Univ New Mexico Hlth Sci Ctr, Albuquerque, NM USA. [Garcia, David] Univ Washington Sch Med, Seattle, WA USA. [Lopes, Renato D.] Duke Univ Med Ctr, Durham, NC USA. [Oertel, Lynn] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Schnurr, Terri; Crowther, Mark] St Josephs Healthcare Hamilton, Hamilton, ON, Canada. [Streiff, Michael] Johns Hopkins Med Ctr, Baltimore, MD USA. [Wirth, Diane] Grady Hlth Syst, Atlanta, GA USA. [Crowther, Mark] McMaster Univ, Hamilton, ON, Canada. RP Nutescu, EA (reprint author), Univ Illinois, Dept Pharm Practice, Ctr Pharmacoepidemiol & Pharmacoecon Res, 833 S Wood St,MC 886,Rm 164, Chicago, IL 60612 USA. EM enutescu@uic.edu NR 5 TC 0 Z9 0 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1060-0280 EI 1542-6270 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD JAN PY 2015 VL 49 IS 1 BP 125 EP 126 DI 10.1177/1060028014548570 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AX0MS UT WOS:000346647000012 PM 25524928 ER PT J AU Kleffel, S Vergani, A Tezza, S Ben Nasr, M Niewczas, MA Wong, S Bassi, R D'Addio, F Schatton, T Abdi, R Atkinson, M Sayegh, MH Wen, L Wasserfall, CH O'Connor, KC Fiorina, P AF Kleffel, Sonja Vergani, Andrea Tezza, Sara Ben Nasr, Moufida Niewczas, Monika A. Wong, Susan Bassi, Roberto D'Addio, Francesca Schatton, Tobias Abdi, Reza Atkinson, Mark Sayegh, Mohamed H. Wen, Li Wasserfall, Clive H. O'Connor, Kevin C. Fiorina, Paolo TI Interleukin-10(+) Regulatory B Cells Arise Within Antigen-Experienced CD40(+) B Cells to Maintain Tolerance to Islet Autoantigens SO DIABETES LA English DT Article ID NONOBESE DIABETIC MICE; DRIVEN HUMORAL RESPONSE; B10 CELLS; LYMPHOCYTE DEPLETION; ANTIBODY PREVENTS; IMMUNE-RESPONSES; PRESENTING CELLS; NOD MOUSE; T-CELLS; IN-VIVO AB Impaired regulatory B cell (Breg) responses are associated with several autoimmune diseases in humans; however, the role of Bregs in type 1 diabetes (T1D) remains unclear. We hypothesized that naturally occurring, interleukin-10 (IL-10)-producing Bregs maintain tolerance to islet autoantigens, and that hyperglycemic nonobese diabetic (NOD) mice and T1D patients lack these potent negative regulators. IgV(H) transcriptome analysis revealed that islet-infiltrating B cells in long-term normoglycemic (Lnglc) NOD, which are naturally protected from diabetes, are more antigen-experienced and possess more diverse B-cell receptor repertoires compared to those of hyperglycemic (Hglc) mice. Importantly, increased levels of Breg-promoting CD40(+) B cells and IL-10-producing B cells were found within islets of Lnglc compared to Hglc NOD. Likewise, healthy individuals showed increased frequencies of both CD40(+) and IL-10(+) B cells compared to T1D patients. Rituximab-mediated B-cell depletion followed by adoptive transfer of B cells from Hglc mice induced hyperglycemia in Lnglc human CD20 transgenic NOD mouse models. Importantly, both murine and human IL-10(+) B cells significantly abrogated T-cell-mediated responses to self- or islet-specific peptides ex vivo. Together, our data suggest that antigen-matured Bregs may maintain tolerance to islet autoantigens by selectively suppressing autoreactive T-cell responses, and that HgIc mice and individuals with T1D lack this population of Bregs. C1 [Kleffel, Sonja; Vergani, Andrea; Tezza, Sara; Ben Nasr, Moufida; Bassi, Roberto; D'Addio, Francesca; Fiorina, Paolo] Harvard Univ, Sch Med, Boston Childrens Hosp, Nephrol Div, Boston, MA 02138 USA. [Vergani, Andrea; D'Addio, Francesca; Fiorina, Paolo] Univ Milan, Osped San Raffaele, Ist Ricovero & Cura Carattere Sci, I-20127 Milan, Italy. [Niewczas, Monika A.] Harvard Univ, Sch Med, Sect Genet & Epidemiol, Joslin Diabet Ctr,Res Div, Boston, MA USA. [Niewczas, Monika A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Wong, Susan] Cardiff Univ, Sch Med, Inst Mol & Expt Med, Cardiff, Wales. [Schatton, Tobias] Harvard Univ, Sch Med, Brigham & Womens Hosp, Harvard Skin Dis Res Ctr,Dep Dermatol, Boston, MA USA. [Schatton, Tobias; Sayegh, Mohamed H.] Harvard Univ, Sch Med, Boston Childrens Hosp, Transplant Res Program, Boston, MA USA. [Abdi, Reza] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Nephrol, Boston, MA USA. [Atkinson, Mark; Wasserfall, Clive H.] Univ Florida, Dept Pathol Immunol & Lab Med, Gainesville, FL USA. [Wen, Li] Yale Sch Med, Dept Immunol, New Haven, CT USA. [O'Connor, Kevin C.] Yale Sch Med, Dept Neurol, New Haven, CT USA. RP Fiorina, P (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Nephrol Div, Boston, MA 02138 USA. EM paolo.fiorina@childrens.harvard.edu RI wasserfall, clive/J-9078-2012; D'Addio, Francesca/F-3417-2017 OI wasserfall, clive/0000-0002-3522-8932; D'Addio, Francesca/0000-0002-0345-0694 FU JDRF Career Development Award; American Society of Nephrology Career Development Award; American Diabetes Association (ADA); American Heart Association (AHA); Boston Children's Hospital; Harvard Stem Cell Institute [DP-0123-12-00]; Italian Ministry of Health [RF-2010-2303119, RF-FSR-2008-1213704]; National Institutes of Health (NIH) [T32-DK-007726-28, RC1DK087699, DK088181]; ADA Mentor-based Fellowship; American Society of Transplantation/Genentech Clinical Science Fellowship grant; JDRF [4-2007-1059] FX P.F. received a JDRF Career Development Award, an American Society of Nephrology Career Development Award, an American Diabetes Association (ADA) Mentor-based Fellowship grant, and is supported by an American Heart Association (AHA) Grant-In-Aid, Translational Research Program (TRP) grant from Boston Children's Hospital, and Harvard Stem Cell Institute grant ("Diabetes Program" DP-0123-12-00). P.F. also received Italian Ministry of Health grants RF-2010-2303119 and "Staminali" RF-FSR-2008-1213704. A.V. has been supported by a National Institutes of Health (NIH) Research Training grant to Boston Children's Hospital in Pediatric Nephrology (T32-DK-007726-28). M.B.N. is supported by an ADA Mentor-based Fellowship grant to P.F. R.B. is supported by an American Society of Transplantation/Genentech Clinical Science Fellowship grant. L.W. is supported by JDRF (4-2007-1059) and NIH (RC1DK087699 and DK088181). NR 52 TC 10 Z9 12 U1 0 U2 9 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 JAN PY 2015 VL 64 IS 1 BP 158 EP 171 DI 10.2337/db13-1639 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX2IB UT WOS:000346765600017 PM 25187361 ER PT J AU Mitra, B Nash, JL Cameron, PA Fitzgerald, MC Moloney, J Velmahos, GC AF Mitra, Biswadev Nash, Jessica L. Cameron, Peter A. Fitzgerald, Mark C. Moloney, John Velmahos, George C. TI Potentially avoidable blood transfusion during trauma resuscitation SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE Wounds and injuries; Transfusion; Blood products; Resuscitation; Emergency; Avoidable; Red blood cells ID NORMOTENSIVE PATIENT UTILITY; PREHOSPITAL SHOCK INDEX; MASSIVE TRANSFUSION; IDENTIFYING RISK; CELL TRANSFUSION; CRITICAL-CARE; MAJOR TRAUMA; GUIDELINE; SEVERITY; TRIAL AB Introduction: Red blood cell (RBC) transfusion is often essential during trauma resuscitation but is associated with high cost and potential adverse outcomes. This study aimed to determine the incidence of potentially avoidable RBC transfusions (PAT) among adult major trauma patients. Materials and methods: A retrospective review of data collected by Registry on patients presenting between Jan 2006 and Dec 2011 was conducted. Eligible patients received at least 1 unit of RBC in the first 24 h following presentation to the Emergency Department (ED). Episodes of PAT were determined according to haemodynamic stability and post-transfusion haemoglobin levels. Results: There were 621 patients included, of whom 224 (36.1%; 95% CI: 32.3-40.0) received PAT. Of them, 132 (58.9%) were haemodynamically stable on arrival and did not require a surgical procedure. Patients with PAT had significantly lower injury severity scores (30 vs 34, p < 0.01), higher presenting systolic blood pressure (129 vs 112 mm Hg, p < 0.01) and a lower frequency of a shock index >= 1 (24.1 vs 65.0%, p < 0.01), compared to those without PAT. They also had a significantly lower mortality (13.4 vs 21.7%, p < 0.01). Conclusions: PAT after trauma was common and often delivered to haemodynamically stable patients who did not require surgical procedures. Clinical decision pathways for trauma resuscitation should aim to limit PAT. (C) 2014 Published by Elsevier Ltd. C1 [Mitra, Biswadev; Nash, Jessica L.; Cameron, Peter A.] Alfred Hosp, Emergency & Trauma Ctr, Melbourne, Vic 3004, Australia. [Mitra, Biswadev; Cameron, Peter A.] Monash Univ, Deparment Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia. [Mitra, Biswadev; Cameron, Peter A.] Hamad Med Corp, Emergency Med, Doha, Qatar. [Cameron, Peter A.; Fitzgerald, Mark C.] Alfred Hosp, Natl Trauma Res Inst, Melbourne, Vic 3004, Australia. [Fitzgerald, Mark C.] Alfred Hosp, Trauma Serv, Melbourne, Vic 3004, Australia. [Moloney, John] Alfred Hosp, Melbourne, Vic 3004, Australia. [Velmahos, George C.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Velmahos, George C.] Harvard Univ, Sch Med, Boston, MA USA. RP Mitra, B (reprint author), Alfred Hosp, Emergency & Trauma Ctr, Commercial Rd, Melbourne, Vic 3004, Australia. EM b.mitra@alfred.org.au OI Fitzgerald, Mark/0000-0003-0183-7761; Mitra, Biswadev/0000-0002-0508-2450 NR 24 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 EI 1879-0267 J9 INJURY JI Injury-Int. J. Care Inj. PD JAN PY 2015 VL 46 IS 1 BP 10 EP 14 DI 10.1016/j.injury.2014.08.050 PG 5 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA AX1YJ UT WOS:000346739600003 PM 25280387 ER PT J AU Morrissey, BE Delaney, RA Johnstone, AJ Petrovick, L Smith, RM AF Morrissey, Brian E. Delaney, Ruth A. Johnstone, Alan J. Petrovick, Laurie Smith, R. Malcolm TI Do trauma systems work? A comparison of major trauma outcomes between Aberdeen Royal Infirmary and Massachusetts General Hospital SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE Trauma systems; Trauma centres; Injury severity score; Penetrating injury; Trauma outcomes ID INJURED PATIENTS; CARE; MORTALITY; PATIENT; REGIONALIZATION; SURVIVAL AB Trauma is an important matter of public health and a major cause of mortality. Since the late 1980s trauma care provision in the United Kingdom is lacking when compared to the USA. This has been attributed to a lack of organisation of trauma care leading to the formation of trauma networks and Major Trauma Centres in England and Wales. The need for similar centres in Scotland is argued currently. We assessed the activity of two quite different trauma systems by obtaining access to comparative data from two hospitals, one in the USA and the other in Scotland. Aggregate data on 5604 patients at Aberdeen Royal Infirmary (ARI) from 1993 to 2002 was obtained from the Scottish Trauma Audit Group. A comparable data set of 16,178 patients from Massachusetts General Hospital (MGH). Direct comparison of patient demographics; injury type, mechanism and Injury Severity Score (ISS); mode of arrival; length of stay and mortality were made. Statistical analysis was carried out using Chi-squared and Cochran-Mantel-Haenszel. There were significant differences in the data sets. There was a higher proportion of penetrating injuries at MGH, (8.6% vs 2.6%) and more severely injured patients at MGH, patients with an ISS > 16 accounted for nearly 22.1% of MGH patients compared to 14.0% at ARI. ISS 8-15 made up 54.6% of ARI trauma with 29.6% at MGH. Falls accounted for 50.1% at ARI and 37.9% at MGH. Despite the higher proportion of severe injuries at MGH and crude mortality rates showing no difference (4.9% ARI vs 5.2% MGH), pooled odds ratio of mortality was 1.4 (95% confidence interval 1.2-1.6) showing worse mortality outcomes at ARI compared to MGH. In conclusion, there were some differences in case mix between both data sets making direct comparison of the outcomes difficult, but the effect of consolidating major trauma on the proportion and number of severely injured patients treated in the American Level 1 centre was clear with a significant improvement in mortality in all injury severity groups. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Morrissey, Brian E.] Univ Aberdeen, Sch Med & Dent, Aberdeen AB25 2ZD, Scotland. [Delaney, Ruth A.; Smith, R. Malcolm] Massachusetts Gen Hosp, Dept Orthopaed Surg, Trauma Serv, Boston, MA 02114 USA. [Johnstone, Alan J.] Aberdeen Royal Infirm, Trauma Orthopaed Unit, Aberdeen AB25 2ZD, Scotland. [Petrovick, Laurie] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. RP Morrissey, BE (reprint author), Univ Aberdeen, Sch Med & Dent, Foresterhill, Aberdeen AB25 2ZD, Scotland. EM brianmorrissey@nhs.net OI Morrissey, Brian/0000-0002-0137-7817 NR 28 TC 2 Z9 2 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 EI 1879-0267 J9 INJURY JI Injury-Int. J. Care Inj. PD JAN PY 2015 VL 46 IS 1 BP 150 EP 155 DI 10.1016/j.injury.2014.08.048 PG 6 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA AX1YJ UT WOS:000346739600028 PM 25270693 ER PT J AU Baxi, SM Liu, A Bacchetti, P Mutua, G Sanders, EJ Kibengo, FM Haberer, JE Rooney, J Hendrix, CW Anderson, PL Huang, Y Priddy, F Gandhi, M AF Baxi, Sanjiv M. Liu, Albert Bacchetti, Peter Mutua, Gaudensia Sanders, Eduard J. Kibengo, Freddie M. Haberer, Jessica E. Rooney, James Hendrix, Craig W. Anderson, Peter L. Huang, Yong Priddy, Frances Gandhi, Monica TI Comparing the Novel Method of Assessing PrEP Adherence/Exposure Using Hair Samples to Other Pharmacologic and Traditional Measures SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE tenofovir; pre-exposure prophylaxis (PrEP); hair; self-report; HIV; medication adherence ID DRIED BLOOD SPOTS; ANTIRETROVIRAL PREEXPOSURE PROPHYLAXIS; HIV PROTEASE INHIBITORS; NUCLEOSIDE-ANALOG; LC-MS/MS; TENOFOVIR; EMTRICITABINE; WOMEN; CHALLENGES; PLASMA AB Objective: The efficacy of pre-exposure prophylaxis (PrEP) in HIV will diminish with poor adherence; pharmacologic measures of drug exposure have proven critical to PrEP trial interpretation. We assessed drug exposure in hair against other pharmacologic and more routinely used measures to assess pill-taking. Design: Participants were randomized to placebo, daily PrEP, or intermittent PrEP to evaluate safety and tolerability of daily versus intermittent tenofovir/emtricitabine (TFV/FTC) in 2 phase II PrEP clinical trials conducted in Africa. Different measures of drug exposure, including self-report, medication event monitoring system (MEMS)-caps openings, and TFV/FTC levels in hair and other biomatrices were compared. Methods: At weeks 8 and 16, self-reported pill-taking, MEMS-caps openings, and TFV/FTC levels in hair, plasma, and peripheral blood mononuclear cells (PBMCs) were measured. Regression models evaluated predictors of TFV/FTC concentrations in the 3 biomatrices; correlation coefficients between pharmacologic and nonpharmacologic measures were calculated. Both trials were registered on ClinicalTrials. gov (NCT00931346/NCT00971230). Results: Hair collection was highly feasible and acceptable (100% in week 8; 96% in week 16). In multivariate analysis, strong associations were seen between pharmacologic measures and MEMS-caps openings (all P < 0.001); self-report was only weakly associated with pharmacologic measures. TFV/FTC hair concentrations were significantly correlated with levels in plasma and PBMCs (correlation coefficients, 0.41-0.86, all P < 0.001). Conclusions: Measuring TFV/FTC exposure in small hair samples in African PrEP trials was feasible and acceptable. Hair levels correlated strongly with PBMC, plasma concentrations, and MEMS-caps openings. As in other PrEP trials, self-report was the weakest measure of exposure. Further study of hair TFV/FTC levels in PrEP trials and demonstration projects to assess adherence/exposure is warranted. C1 [Baxi, Sanjiv M.; Gandhi, Monica] Univ Calif San Francisco, Div HIV AIDS, Dept Med, San Francisco, CA 94110 USA. [Baxi, Sanjiv M.; Gandhi, Monica] Univ Calif San Francisco, Div Infect Dis, Dept Med, San Francisco, CA 94110 USA. [Liu, Albert] San Francisco Dept Publ Hlth, San Francisco, CA USA. [Bacchetti, Peter] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94110 USA. [Mutua, Gaudensia] Kenya AIDS Vaccine Initiat, Nairobi, Kenya. [Sanders, Eduard J.] Kenya Govt Med Res Ctr, Ctr Geog Med Res Coast, Kilifi, Kenya. [Sanders, Eduard J.] Univ Oxford, Nuffield Dept Clin Med, Headington, England. [Kibengo, Freddie M.] MRC UVRI Uganda Res Unit AIDS, Entebbe, Uganda. [Haberer, Jessica E.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Rooney, James] Gilead Sci, Foster City, CA USA. [Hendrix, Craig W.] Johns Hopkins Univ, Sch Med, Dept Med, Div Clin Pharmacol, Baltimore, MD 21205 USA. [Anderson, Peter L.] Univ Colorado, Dept Pharmaceut Sci, Aurora, CO USA. [Huang, Yong] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94110 USA. [Priddy, Frances] Int AIDS Vaccine Initiat, New York, NY USA. RP Gandhi, M (reprint author), Univ Calif San Francisco, Div HIV AIDS, San Francisco Gen Hosp, 995 Potrero Ave,4th Floor, San Francisco, CA 94110 USA. EM monica.gandhi@ucsf.edu RI Hendrix, Craig/G-4182-2014 OI Hendrix, Craig/0000-0002-5696-8665 FU International AIDS Vaccine Initiative (IAVI); Bill & Melinda Gates Foundation; Ministry of Foreign Affairs of Denmark; Irish Aid; Ministry of Finance of Japan; Ministry of Foreign Affairs of the Netherlands; Norwegian Agency for Development Cooperation (NORAD); United Kingdom Department for International Development (DFID); United States Agency for International Development (USAID); Gilead Sciences; National Institute of Allergy and Infectious Diseases (NIAID)/National Institutes of Health (NIH) [R01 AI098472]; UCSF Traineeship in AIDS Prevention Studies (US National Institutes of Health (NIH)) [T32 MH-19105]; Wellcome Trust [077092] FX Supported and sponsored by the International AIDS Vaccine Initiative (IAVI). IAVI's work is made possible by generous support from many donors including: the Bill & Melinda Gates Foundation; the Ministry of Foreign Affairs of Denmark; Irish Aid; the Ministry of Finance of Japan; the Ministry of Foreign Affairs of the Netherlands; the Norwegian Agency for Development Cooperation (NORAD); the United Kingdom Department for International Development (DFID), and the United States Agency for International Development (USAID). The full list of IAVI donors is available at www.iavi.org. Support in the form of study medication was provided by Gilead Sciences. Funding for the hair assays and statistical analyses was provided by the National Institute of Allergy and Infectious Diseases (NIAID)/National Institutes of Health (NIH) (R01 AI098472 to M.G.). The Women's Interagency HIV Study (NIH U01AI034989) contributed to hair assay development. S.M.B. is supported by the UCSF Traineeship in AIDS Prevention Studies (US National Institutes of Health (NIH) T32 MH-19105). The KWTRP at the Centre for Geographical Medicine Research, Kilifi is supported by core funding from the Wellcome Trust (#077092). NR 57 TC 7 Z9 7 U1 3 U2 12 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 JAN 1 PY 2015 VL 68 IS 1 BP 13 EP 20 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AX0LL UT WOS:000346643800010 PM 25296098 ER PT J AU Jain, S Oldenburg, CE Mimiaga, MJ Mayer, KH AF Jain, Sachin Oldenburg, Catherine E. Mimiaga, Matthew J. Mayer, Kenneth H. TI Longitudinal Trends in HIV Nonoccupational Postexposure Prophylaxis Use at a Boston Community Health Center Between 1997 and 2013 SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE PEP; NPEP; postexposure prophylaxis; HIV; biomedical prevention ID SEXUAL EXPOSURE; RISK BEHAVIOR; ANTIRETROVIRAL PROPHYLAXIS; ZIDOVUDINE-LAMIVUDINE; MALE CIRCUMCISION; HOMOSEXUAL-MEN; TENOFOVIR DF; PREVENTION; INFECTION; TOLERABILITY AB Secular trends in nonoccupational postexposure prophylaxis (NPEP) use have not been well characterized. We performed a retrospective longitudinal study of 894 electronic medical records of NPEP users, mostly men who have sex with men, at a Boston community health center who presented between July 1997 and August 2013. NPEP use and condomless sexual exposures increased over time; 19.4% had multiple NPEP courses. Having an HIV-infected partner was associated with increased odds of regimen completion, and 3-drug regimens were associated with decreased odds of completion. Targeted adherence and risk-reduction counseling are warranted for select NPEP users at this center. C1 [Jain, Sachin; Mayer, Kenneth H.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. [Jain, Sachin; Oldenburg, Catherine E.; Mimiaga, Matthew J.; Mayer, Kenneth H.] Fenway Inst, Boston, MA USA. [Jain, Sachin; Mimiaga, Matthew J.; Mayer, Kenneth H.] Harvard Univ, Sch Med, Boston, MA USA. [Oldenburg, Catherine E.; Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Mimiaga, Matthew J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Jain, S (reprint author), Montefiore Med Ctr, AIDS Ctr, 3444 Kossuth Ave, Bronx, NY 10467 USA. EM sajain@montefiore.org FU National Institute of Allergy and Infectious Disease T32 NRSA grant [T32AI007535]; National Institute of Drug Abuse T32 NRSA grant [T32DA0131911]; Harvard University Center For AIDS Research (CFAR), an NIH [P30 AI060354] FX C.E.O. is supported by a National Institute of Allergy and Infectious Disease T32 NRSA grant (T32AI007535; PI: Seage) and a National Institute of Drug Abuse T32 NRSA grant (T32DA0131911; PI: Flanigan). K.H.M. receives funding from the Harvard University Center For AIDS Research (CFAR), an NIH funded program (P30 AI060354; PI: Walker). The remaining authors have no funding or conflicts of interest to disclose. NR 39 TC 7 Z9 7 U1 2 U2 6 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 JAN 1 PY 2015 VL 68 IS 1 BP 97 EP 101 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AX0LL UT WOS:000346643800021 PM 25321180 ER PT J AU Buchan, SL Manzo, T Flutter, B Rogel, A Edwards, N Zhang, L Sivakumaran, S Ghorashian, S Carpenter, B Bennett, CL Freeman, GJ Sykes, M Croft, M Al-Shamkhani, A Chakraverty, R AF Buchan, Sarah L. Manzo, Teresa Flutter, Barry Rogel, Anne Edwards, Noha Zhang, Lei Sivakumaran, Shivajanani Ghorashian, Sara Carpenter, Ben Bennett, Clare L. Freeman, Gordon J. Sykes, Megan Croft, Michael Al-Shamkhani, Aymen Chakraverty, Ronjon TI OX40-and CD27-Mediated Costimulation Synergizes with Anti-PD-L1 Blockade by Forcing Exhausted CD8(+) T Cells To Exit Quiescence SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHRONIC VIRAL-INFECTION; MOLECULAR SIGNATURE; DENDRITIC CELLS; CO-STIMULATION; EXPRESSION; RESPONSES; SURVIVAL; MEMORY; ACTIVATION; EXPANSION AB Exhaustion of chronically stimulated CD8(+) T cells is a significant obstacle to immune control of chronic infections or tumors. Although coinhibitory checkpoint blockade with anti-programmed death ligand 1 (PD-L1) Ab can restore functions to exhausted T cell populations, recovery is often incomplete and dependent upon the pool size of a quiescent T-bet(high) subset that expresses lower levels of PD-1. In a model in which unhelped, HY-specific CD8(+) T cells gradually lose function following transfer to male bone marrow transplantation recipients, we have explored the effect of shifting the balance away from coinhibition and toward costimulation by combining anti-PD-L1 with agonistic Abs to the TNFR superfamily members, OX40 and CD27. Several weeks following T cell transfer, both agonistic Abs, but especially anti-CD27, demonstrated synergy with anti-PD-L1 by enhancing CD8(+) T cell proliferation and effector cytokine generation. Anti-CD27 and anti-PD-L1 synergized by downregulating the expression of multiple quiescence-related genes concomitant with a reduced frequency of T-bet(high) cells within the exhausted population. However, in the presence of persistent Ag, the CD8(+) T cell response was not sustained and the overall size of the effector cytokine-producing pool eventually contracted to levels below that of controls. Thus, CD27-mediated costimulation can synergize with coinhibitory checkpoint blockade to switch off molecular programs for quiescence in exhausted T cell populations, but at the expense of losing precursor cells required to maintain a response. C1 [Buchan, Sarah L.; Rogel, Anne; Al-Shamkhani, Aymen] Univ Southampton, Canc Sci Unit, Fac Med, Southampton SO17 1BJ, Hants, England. [Manzo, Teresa; Flutter, Barry; Edwards, Noha; Zhang, Lei; Sivakumaran, Shivajanani; Ghorashian, Sara; Carpenter, Ben; Bennett, Clare L.; Chakraverty, Ronjon] UCL, Inst Canc, Transplantat Immunol Grp, London NW3 2PF, England. [Manzo, Teresa; Flutter, Barry; Edwards, Noha; Zhang, Lei; Sivakumaran, Shivajanani; Ghorashian, Sara; Carpenter, Ben; Bennett, Clare L.; Chakraverty, Ronjon] UCL, Inst Immun & Transplantat, London NW3 2PF, England. [Freeman, Gordon J.] Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Sch Med, Boston, MA 02115 USA. [Sykes, Megan] Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, New York, NY 10032 USA. [Croft, Michael] Inst Allergy & Immunol, La Jolla, CA 92037 USA. RP Chakraverty, R (reprint author), UCL, Inst Canc, Transplantat Immunol Grp, London NW3 2PF, England. EM r.chakraverty@ucl.ac.uk FU Leukaemia and Lymphoma Research; National Institutes of Health [P01 AI56299, R01 A1051559]; National Institutes of Health/National Cancer Institute [P01 CA111519] FX This work was supported by Leukaemia and Lymphoma Research (to R.C., A.A.-S., and S.L.B.), National Institutes of Health Grants P01 AI56299 and R01 A1051559 (to G.J.F.), and National Institutes of Health/National Cancer Institute Grant P01 CA111519 (to M.S.). NR 43 TC 18 Z9 18 U1 3 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2015 VL 194 IS 1 BP 125 EP 133 DI 10.4049/jimmunol.1401644 PG 9 WC Immunology SC Immunology GA AX1IH UT WOS:000346700500015 PM 25404365 ER PT J AU Dugan, J Griffiths, E Snow, P Rosenzweig, H Lee, E Brown, B Carr, DW Rose, C Rosenbaum, J Davey, MP AF Dugan, Jae Griffiths, Eric Snow, Paige Rosenzweig, Holly Lee, Ellen Brown, Brieanna Carr, Daniel W. Rose, Carlos Rosenbaum, James Davey, Michael P. TI Blau Syndrome-Associated Nod2 Mutation Alters Expression of Full-Length NOD2 and Limits Responses to Muramyl Dipeptide in Knock-in Mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NF-KAPPA-B; EARLY-ONSET SARCOIDOSIS; CROHNS-DISEASE; SIGNALING PATHWAYS; CARD15 MUTATIONS; MURINE MODEL; ACTIVATION; PROTEINS; SUSCEPTIBILITY; PEPTIDOGLYCAN AB The biochemical mechanism by which mutations in nucleotide-binding oligomerization domain containing 2 (NOD2) cause Blau syndrome is unknown. Several studies have examined the effect of mutations associated with Blau syndrome in vitro, but none has looked at the implication of the mutations in vivo. To test the hypothesis that mutated NOD2 causes alterations in signaling pathways downstream of NOD2, we created a Nod2 knock-in mouse carrying the most common mutation seen in Blau syndrome, R314Q (corresponding to R334Q in humans). The endogenous regulatory elements of mouse Nod2 were unaltered. R314Q mice showed reduced cytokine production in response to i.p. and intravitreal muramyl dipeptide (MDP). Macrophages from R314Q mice showed reduced NF-kappa B and IL-6 responses, blunted phosphorylation of MAPKs, and deficient ubiquitination of receptorinteracting protein 2 in response to MDP. R314Q mice expressed a truncated 80-kDa form of NOD2 that was most likely generated by a posttranslational event because there was no evidence for a stop codon or alternative splicing event. Human macrophages from two patients with Blau syndrome also showed a reduction of both cytokine production and phosphorylation of p38 in response to MDP, indicating that both R314Q mice and cells from patients with Blau syndrome show reduced responses to MDP. These data indicate that the R314Q mutation when studied with the Nod2 endogenous regulatory elements left intact is associated with marked structural and biochemical changes that are significantly different from those observed from studies of the mutation using overexpression, transient transfection systems. C1 [Dugan, Jae; Griffiths, Eric; Snow, Paige; Rosenzweig, Holly; Carr, Daniel W.; Davey, Michael P.] Portland VA Med Ctr, Portland, OR 97239 USA. [Dugan, Jae; Carr, Daniel W.; Rosenbaum, James; Davey, Michael P.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Rosenzweig, Holly; Lee, Ellen; Brown, Brieanna; Rosenbaum, James] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97239 USA. [Rosenzweig, Holly; Davey, Michael P.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. [Rose, Carlos] DuPont Hosp Children, Div Rheumatol, Wilmington, DE 19803 USA. [Rosenbaum, James] Legacy Devers Eye Inst, Portland, OR 97210 USA. RP Davey, MP (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM michael.davey@va.gov OI Snow, Paige/0000-0001-9836-7705 FU Department of Veterans Affairs Biomedical Laboratory Research and Development Service [5 IK2 BX001295, 5 I01 BX000229]; National Institutes of Health [5-T32-AI07472] FX This work was supported by Career Development (5 IK2 BX001295) and Merit Review (5 I01 BX000229) Awards from the Department of Veterans Affairs Biomedical Laboratory Research and Development Service as well as National Institutes of Health Training Grant 5-T32-AI07472. NR 52 TC 2 Z9 2 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2015 VL 194 IS 1 BP 349 EP 357 DI 10.4049/jimmunol.1402330 PG 9 WC Immunology SC Immunology GA AX1IH UT WOS:000346700500037 PM 25429073 ER PT J AU Cooley, ME Blonquist, TM Catalano, PJ Lobach, DF Halpenny, B McCorkle, R Johns, EB Braun, IM Rabin, MS Mataoui, FZ Finn, K Berry, DL Abrahm, JL AF Cooley, Mary E. Blonquist, Traci M. Catalano, Paul J. Lobach, David F. Halpenny, Barbara McCorkle, Ruth Johns, Ellis B. Braun, Ilana M. Rabin, Michael S. Mataoui, Fatma Zohra Finn, Kathleen Berry, Donna L. Abrahm, Janet L. TI Feasibility of Using Algorithm-Based Clinical Decision Support for Symptom Assessment and Management in Lung Cancer SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Palliative care; symptom management; lung cancer; clinical decision support; clinical practice guidelines ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; EVIDENCE-BASED RECOMMENDATIONS; EVIDENCE-BASED GUIDELINES; PALLIATIVE CARE; ONCOLOGY PRACTICE; PAIN MANAGEMENT; AMERICAN SOCIETY; CHRONIC DISEASE; DEPRESSION AB Context. Distressing symptoms interfere with the quality of life in patients with lung cancer. Algorithm-based clinical decision support (CDS) to improve evidence-based management of isolated symptoms seems promising, but no reports yet address multiple symptoms. Objectives. This study examined the feasibility of CDS for a Symptom Assessment and Management Intervention targeting common symptoms in patients with lung cancer (SAMI-L) in ambulatory oncology. The study objectives were to evaluate completion and delivery rates of the SAMI-L report and clinician adherence to the algorithm-based recommendations. Methods. Patients completed a web-based symptom assessment and SAMI-L created tailored recommendations for symptom management. Completion of assessments and delivery of reports were recorded. Medical record review assessed clinician adherence to recommendations. Feasibility was defined as 75% or higher report completion and delivery rates and 80% or higher clinician adherence to recommendations. Descriptive statistics and generalized estimating equations were used for data analyses. Results. Symptom assessment completion was 84% (95% CI = 81-87%). Delivery of completed reports was 90% (95% CI = 86-93%). Depression (36%), pain (30%), and fatigue (18%) occurred most frequently, followed by anxiety (11%) and dyspnea (6%). On average, overall recommendation adherence was 57% (95% CI = 52-62%) and was not dependent on the number of recommendations (P = 0.45). Adherence was higher for anxiety (66%; 95% CI = 55-77%), depression (64%; 95% CI = 56-71%), pain (62%; 95% CI = 52-72%), and dyspnea (51%; 95% CI = 38-64%) than for fatigue (38%; 95% CI = 28-47%). Conclusion. The CDS systems, such as SAMI-L, have the potential to fill a gap in promoting evidence-based care. (C) 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved. C1 [Cooley, Mary E.; Blonquist, Traci M.; Catalano, Paul J.; Halpenny, Barbara; Braun, Ilana M.; Rabin, Michael S.; Berry, Donna L.; Abrahm, Janet L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mataoui, Fatma Zohra] Univ Massachusetts, Boston, MA 02125 USA. [Finn, Kathleen] Boston Med Ctr, Boston, MA USA. [Lobach, David F.] Religent Hlth, Durham, NC USA. [McCorkle, Ruth] Yale Univ, New Haven, CT USA. [Johns, Ellis B.] Virginia Commonwealth Univ Shenandoah Valley, Front Royal, VA USA. RP Cooley, ME (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,LW-512, Boston, MA 02115 USA. EM mary_cooley@dfci.harvard.edu FU National Cancer Institute grant [R01 CA125256]; Mentored Career Development Award [R01 CA125256, 1 K07 CA92696] FX This study was supported by National Cancer Institute grant R01 CA125256 (PI: M. E. Cooley). The R01 CA125256 grant was prepared as part of a Mentored Career Development Award (1 K07 CA92696-M. E. Cooley), Karen M. Emmons, PhD and Bruce E. Johnson, MD, Mentors. The authors declare no conflicts of interest. NR 74 TC 5 Z9 5 U1 3 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD JAN PY 2015 VL 49 IS 1 BP 13 EP 26 DI 10.1016/j.jpainsymman.2014.05.003 PG 14 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA AX1ZI UT WOS:000346742500002 PM 24880002 ER PT J AU Rosenberg, AR Postier, A Osenga, K Kreicbergs, U Neville, B Dussel, V Wolfe, J AF Rosenberg, Abby R. Postier, Andrea Osenga, Kaci Kreicbergs, Ulrika Neville, Bridget Dussel, Veronica Wolfe, Joanne TI Long-Term Psychosocial Outcomes Among Bereaved Siblings of Children With Cancer SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Bereavement; siblings; pediatric cancer; psychological distress; resilience; psychosocial outcomes; survivorship ID POSTTRAUMATIC STRESS SYMPTOMS; CHILDHOOD-CANCER; PSYCHOLOGICAL DISTRESS; FOLLOW-UP; PARENTS; CARE; DEATH; POPULATION; NATIONWIDE; ADJUSTMENT AB Context.. The death of a child from cancer affects the entire family. Little is known about the long-term psychosocial outcomes of bereaved siblings. Objectives. To describe 1) the prevalence of risky health behaviors, psychological distress, and social support among bereaved siblings and 2) potentially modifiable factors associated with poor outcomes. Methods. Bereaved siblings were eligible for this dual-center, cross-sectional, survey-based study if they were 16 years or older and their parents had enrolled in one of three prior studies about caring for children with cancer at the end of life. Linear regression models identified associations between personal perspectives before, during, and after the family's cancer experience and outcomes (health behaviors, psychological distress, and social support). Results. Fifty-eight siblings completed surveys (62% response rate). They were approximately 12 years bereaved, with a mean age of 26 years at the time of the survey (SD 7.8). Anxiety, depression, and illicit substance use increased during the year after their brother/sister's death but then returned to baseline. Siblings who reported dissatisfaction with communication, poor preparation for death, missed opportunities to say goodbye, and/or a perceived negative impact of the cancer experience on relationships tended to have higher distress and lower social support scores (P < 0.001-0.031). Almost all siblings reported that their loss still affected them; half stated that the experience impacted current educational and career goals. Conclusion. How siblings experience the death of a child with cancer may impact their long-term psychosocial well-being. Sibling-directed communication and concurrent supportive care during the cancer experience and the year after the sibling death may mitigate poor long-term outcomes. (C) 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved. C1 [Rosenberg, Abby R.] Seattle Childrens Hosp, Seattle, WA USA. [Rosenberg, Abby R.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Rosenberg, Abby R.] Treuman Katz Ctr Pediat Bioeth, Seattle, WA USA. [Rosenberg, Abby R.] Univ Washington, Seattle, WA 98195 USA. [Postier, Andrea; Osenga, Kaci] Childrens Hosp & Clin Minnesota, Dept Pain Med Palliat Care & Integrat Med, Minneapolis, MN USA. [Kreicbergs, Ulrika] Karolinska Inst, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, Stockholm, Sweden. [Kreicbergs, Ulrika] Sophiahemmet Univ, Stockholm, Sweden. [Neville, Bridget; Wolfe, Joanne] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Dussel, Veronica; Wolfe, Joanne] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Dussel, Veronica] Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina. [Wolfe, Joanne] Boston Childrens Hosp, Dept Med, Boston, MA USA. RP Wolfe, J (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Psychosocial Oncol & Palliat Care, 450 Brookline Ave, Boston, MA 02215 USA. EM joanne_wolfe@dfci.harvard.edu FU NCI NIH HHS [L40 CA170049] NR 35 TC 10 Z9 10 U1 9 U2 41 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD JAN PY 2015 VL 49 IS 1 BP 56 EP 66 DI 10.1016/j.jpainsymman.2014.05.006 PG 11 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA AX1ZI UT WOS:000346742500006 PM 24880001 ER PT J AU Paudel, BD Ryan, KM Brown, MS Krakauer, EL Rajagopal, MR Maurer, MA Cleary, JF AF Paudel, Bishnu Dutta Ryan, Karen M. Brown, Mary Skemp Krakauer, Eric L. Rajagopal, M. R. Maurer, Martha A. Cleary, James F. TI Opioid Availability and Palliative Care in Nepal: Influence of an International Pain Policy Fellowship SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Morphine; Nepal; opioid availability; International Pain Policy Fellowship; Low- and middle-income countries ID MAPPING LEVELS AB Globally, cancer incidence and mortality are increasing, and most of the burden is shifting to low-and middle-income countries (LMICs), where patients often present with late-stage disease and severe pain. Unfortunately, LMICs also face a disproportionate lack of access to pain-relieving medicines such as morphine, despite the medical and scientific literature that shows morphine to be effective to treat moderate and severe cancer pain. In 2008, an oncologist from Nepal, one of the poorest countries in the world, was selected to participate in the International Pain Policy Fellowship, a program to assist LMICs, to improve patient access to pain medicines. Following the World Health Organization public health model for development of pain relief and palliative care, the Fellow, working with colleagues and mentors, has achieved initial successes: three forms of oral morphine (syrup, immediate-release tablets, and sustained-release tablets) are now manufactured in the country; health-care practitioners are receiving training in the use of opioids for pain relief; and a new national palliative care association has developed a palliative care training curriculum. However, long-term implementation efforts, funding, and technical assistance by governments, philanthropic organizations, and international partners are necessary to ensure that pain relief and palliative care become accessible by all in need in Nepal and other LMICs. (C) 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved. C1 [Paudel, Bishnu Dutta] Minist Hlth, Bir Hosp, Natl Acad Med Sci, Kathmandu, Nepal. [Ryan, Karen M.] Univ Wisconsin, Res & Sponsored Programs, Madison, WI USA. [Brown, Mary Skemp; Maurer, Martha A.; Cleary, James F.] Univ Wisconsin, Carbone Canc Ctr, World Hlth Org Collaborating Ctr Pain Policy Pall, Pain & Policy Studies Grp, Madison, WI USA. [Krakauer, Eric L.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. Massachusetts Gen Hosp, Palliat Care Unit, Boston, MA 02114 USA. [Rajagopal, M. R.] Pallium India World Hlth Org Collaborating Ctr Tr, Trivandrum Inst Palliat Care, Trivandrum, Kerala, India. RP Maurer, MA (reprint author), Pain & Policy Studies Grp, 1300 Univ Ave,6152 MSC, Madison, WI 53706 USA. EM mamaurer@uwcarbone.wisc.edu FU LIVESTRONG Foundation; Open Society Foundation; Purdue Pharma FX The authors acknowledge the contributions of Mr. David Joranson, the founder and former director of PPSG, for his work with Dr. Paudel and his review of the manuscript. The authors gratefully acknowledge funding for the IPPF from LIVESTRONG and the Open Society Foundations. Drs. Paudel, Krakauer and Rajagopal have no conflicts of interest to report.; The University of Wisconsin Carbone Cancer Center has received unrestricted educational grants from Purdue Pharma to support the work of the Pain & Policy Studies Group (PPSG); this relationship ended in 2010. (Drs. Maurer and Cleary and Mr. Skemp Brown are members of PPSG staff; Ms. Ryan was a member of PPSG staff until September 2012.) NR 24 TC 4 Z9 4 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD JAN PY 2015 VL 49 IS 1 BP 111 EP 117 DI 10.1016/j.jpainsymman.2014.02.011 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA AX1ZI UT WOS:000346742500011 PM 24768596 ER PT J AU Accordino, RE Walkup, JT AF Accordino, Robert E. Walkup, John T. TI The Medical and Psychiatric Evaluation of the Nonverbal Child SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material ID PAIN; AUTISM C1 [Accordino, Robert E.] Massachusetts Gen Hosp, Yawkey Outpatient Care Ctr, Child & Adolescent Psychiat Serv, Boston, MA 02114 USA. [Walkup, John T.] Weill Cornell Med Coll, Div Child & Adolescent Psychiat, New York, NY USA. [Walkup, John T.] New York Presbyterian Hosp, New York, NY USA. RP Accordino, RE (reprint author), Massachusetts Gen Hosp, Yawkey Outpatient Care Ctr, Yaw 6A,32 Fruit St, Boston, MA 02114 USA. EM raccordino@partners.org NR 5 TC 2 Z9 2 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 EI 1527-5418 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JAN PY 2015 VL 54 IS 1 BP 3 EP 5 DI 10.1016/j.jaac.2014.09.018 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA AX3DJ UT WOS:000346820400001 PM 25524783 ER PT J AU Li, XN Eichinger, JK Hartshorn, T Zhou, HB Matzkin, EG Warner, JP AF Li, Xinning Eichinger, Jogef K. Hartshorn, Timothy Zhou, Hanbing Matzkin, Elizabeth G. Warner, Jon P. TI A Comparison of the Lateral Decubitus and Beach-chair Positions for Shoulder Surgery: Advantages and Complications SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Review ID CEREBRAL OXYGEN DESATURATION; NEAR-INFRARED SPECTROSCOPY; SITTING POSITION; INTERSCALENE BLOCK; ARTHROSCOPY; DECOMPRESSION; ANESTHESIA; PATIENT; EVENTS; NERVE AB Arthroscopic or open shoulder surgery can be performed using the lateral decubitus or beach-chair position. Advantages of the lateral decubitus position include better visualization and instrument access for certain procedures and decreased risk for cerebral hypoperfusion. Complications associated with this position include traction injuries, resulting in neurapraxia, thromboembolic events, difficulty with airway management, and the potential need to convert to an anterior open approach. One advantage of the beach-chair position is easier setup from a supine to upright position, which allows the surgeon the option to convert to an open procedure if necessary. Although rare, patients in this position may experience cerebral hypoperfusion and complications that range from cranial nerve injury to infarction. Other complications related to this position include cervical traction neurapraxia, blindness, and cardiac and embolic events. The surgeon must be cognizant of the complications associated with both positions and take extra care in the initial patient setup and coordination with the anesthesiologist to minimize the risk of complications and morbidity. C1 [Li, Xinning] Boston Univ, Sch Med, Dept Orthopaed Surg, Boston, MA 02118 USA. [Matzkin, Elizabeth G.] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Warner, Jon P.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Eichinger, Jogef K.] Madigan Army Med Ctr, Orthopaed Surg Serv, Tacoma, WA 98431 USA. [Hartshorn, Timothy] Ventura Cty Med Ctr, Dept Orthopaed Surg, Ventura, CA USA. [Zhou, Hanbing] Univ Massachusetts, Med Ctr, Dept Orthoped & Phys Rehabil, Worcester, MA USA. RP Li, XN (reprint author), Boston Univ, Sch Med, Dept Orthopaed Surg, Boston, MA 02118 USA. FU ArthroCare; DJO Global; Arthrex; DePuy Mitek; Breg; Smith Nephew; Tornier FX Dr. Li or an immediate family member serves as a paid consultant to DePuy Mitek and Tornier. Dr. Warner or an immediate family member has received royalties from Tornier; has received nonincome support (such as equipment or services), commercially derived honoraria, or other non-research related funding (such as paid travel) from ArthroCare, DJO Global, Arthrex, DePuy Mitek, Breg, Smith & Nephew, and Tornier; and serves as a board member, owner, officer, or committee member of the American Shoulder and Elbow Surgeons and the San Diego Shoulder Institute. None of the following authors or any immediate family member has received anything of value from or has stock or stock options held in a commercial company or institution related directly or indirectly to the subject of this article: Dr. Eichinger, Dr. Hartshorn, Dr. Zhou, and Dr. Matzkin. NR 54 TC 7 Z9 7 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1067-151X EI 1940-5480 J9 J AM ACAD ORTHOP SUR JI J. Am. Acad. Orthop. Surg. PD JAN PY 2015 VL 23 IS 1 BP 18 EP 28 DI 10.5435/JAAOS-23-01-18 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AX4DF UT WOS:000346883400003 PM 25538127 ER PT J AU Robinson, WP Huang, W Rosen, A Schanzer, A Fang, H Anderson, FA Messina, LM AF Robinson, William P. Huang, Wei Rosen, Amy Schanzer, Andres Fang, Hua Anderson, Frederick A. Messina, Louis M. TI The Agency for Healthcare Research and Quality Inpatient Quality Indicator #11 overall mortality rate does not accurately assess mortality risk after abdominal aortic aneurysm repair SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID ENDOVASCULAR REPAIR; RUPTURE; PERFORMANCE; PREDICTION; VALIDATION; SCORE AB Objective: The Agency for Healthcare Research and Quality (AHRQ) Inpatient Quality Indicator (IQI) #11, abdominal aortic aneurysm (AAA) repair mortality rate, is a measure of hospital quality that is publically reported but has not been externally validated. Because the IQI #11 overall mortality rate includes both intact and ruptured aneurysms and open and endovascular repair, we hypothesized that IQI #11 overall mortality rate does not provide accurate assessment of mortality risk after AAA repair and that AAA mortality cannot be accurately assessed by a single quality measure. Methods: Using AHRQ IQI software version 4.2, we calculated observed (O) and expected (E) mortality rates for IQI #11 for all hospitals performing more than 10 AAA repairs per year in the Nationwide Inpatient Sample for the years 2007 to 2011. We used Spearman correlation coefficient to compare expected rates as determined by IQI #11 overall mortality rate risk adjustment methodology and observed rates for all AAA repairs in four cohorts stratified by aneurysm stability (ruptured vs intact) and method of repair (open vs endovascular). Results: Among 187,773 AAA repairs performed at 1268U.S. hospitals, hospitals' IQI #11 overall expected rates correlated poorly with their observed rates (E: 5.0% +/- 4.4% vsO: 6.0% +/- 9.8%; r=.49). For ruptured AAAs, IQI #11 overall mortality rate methodology underestimated the mortality risk of open repair (E: 34% +/- 7.2% vs O: 40.1% +/- 38.2%; r = 0.20) and endovascular repair (E: 24.8% 6 9% vs O: 27.3% 6 37.9%; r = 0.08). For intact AAA repair, IQI #11 overall mortality rate methodology underestimated the mortality risk of open repair (E: 4.3% +/- 2.4% vs O: 6.3% +/- 16.1%; r = .24) but overestimated the mortality risk of endovascular repair (E: 1.3% +/- 0.8% vs O: 1.1% +/- 3.7%; r = 0.25). Hospitals' observed mortality rates after intact AAA repair were not correlated with their mortality rates after ruptured AAA repair (r = 0.03). Conclusions: IQI #11 overall mortality rate fails to provide accurate assessment of inpatient mortality risk after AAA repair. Thus, it is inappropriate to use IQI #11 overall mortality rate for quality reporting. The accuracy of separate quality measures that assess mortality risk after repair of ruptured and intact AAAs, stratified by the use of open or endovascular repair, should be examined. C1 [Robinson, William P.; Schanzer, Andres; Messina, Louis M.] Univ Massachusetts, Sch Med, Div Vasc & Endovasc Surg, Worcester, MA 01655 USA. [Huang, Wei; Anderson, Frederick A.] Univ Massachusetts, Sch Med, Ctr Outcomes Res, Worcester, MA 01655 USA. [Rosen, Amy; Schanzer, Andres; Fang, Hua] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA 01655 USA. [Rosen, Amy] VA Boston Healthcare Syst, Boston, MA USA. RP Robinson, WP (reprint author), Univ Massachusetts, Sch Med, UMass Mem Med Ctr, Div Vasc & Endovasc Surg, 55 Lake Ave N, Worcester, MA 01655 USA. EM william.robinson@umassmemorial.org NR 20 TC 2 Z9 2 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JAN PY 2015 VL 61 IS 1 BP 45 EP 50 DI 10.1016/j.jvs.2014.06.106 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA AX0JB UT WOS:000346637600007 PM 25065583 ER PT J AU Nosova, EV Conte, MS Grenon, SM AF Nosova, Emily V. Conte, Michael S. Grenon, S. Marlene TI Advancing beyond the "heart-healthy diet" for peripheral arterial disease SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; POLYUNSATURATED FATTY-ACIDS; CARDIOVASCULAR-DISEASE; ENDOTHELIAL FUNCTION; RISK-FACTORS; VITAMIN-D; BLOOD-PRESSURE; UNITED-STATES; FOLIC-ACID; OMEGA-3-FATTY-ACID SUPPLEMENTATION AB Objective: Peripheral arterial disease (PAD) is a burdensome cardiovascular condition that results from chronic inflammatory insults to the arterial vasculature. Key risk factors include age, gender, type 2 diabetes mellitus, hypertension, hypercholesterolemia, hyperhomocysteinemia, smoking, lack of physical fitness, and poor diet, the latter three being modifiable in the development and progression of PAD. A growing body of evidence indicates that imbalanced nutrient intake may contribute to the development and progression of PAD. The purpose of this review is to summarize current knowledge about nutritional patterns among patients with PAD and to ascertain whether certain health-promoting foods and nutrients could benefit patients with this condition. Methods: We conducted a comprehensive literature review to examine primary source evidence for or against the nutrients that are commonly associated with PAD and their potential utility as therapies. Results: We summarized nine categories of nutrients, as well as four diets endorsed by the American Heart Association that may be prescribed to patients with or at risk for PAD. The nutrients reviewed included omega-3 polyunsaturated fatty acids (n-3 PUFAs), folate and B-series vitamins, and antioxidants. The diet plans described include the Dietary Approaches to Stop Hypertension (DASH) diet, Mediterranean diet, low-fat diet, low carbohydrate diet, Dr Dean Ornish's Spectrum Diet and Dr Andrew Weil's Anti-Inflammatory Diet. Conclusions: PAD is a chronic inflammatory condition that is associated with longstanding poor nutrition habits. We advocate for an intensified use of diet in PAD therapy, and we specifically recommend following eating patterns that are rich in nutrients with anti-inflammatory and antioxidant properties. C1 [Nosova, Emily V.; Conte, Michael S.; Grenon, S. Marlene] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Nosova, Emily V.; Grenon, S. Marlene] Univ Calif San Francisco, VIPERx Lab, San Francisco, CA 94143 USA. [Conte, Michael S.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Grenon, S. Marlene] San Francisco VA Med Ctr, Dept Surg, San Francisco, CA 94121 USA. RP Grenon, SM (reprint author), San Francisco VA Med Ctr, Mail Code 112G,4150 Clement St, San Francisco, CA 94121 USA. EM marlene.grenon@ucsfmedctr.org FU NHLBI NIH HHS [K23 HL122446] NR 86 TC 0 Z9 0 U1 4 U2 20 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JAN PY 2015 VL 61 IS 1 BP 265 EP 274 DI 10.1016/j.jvs.2014.10.022 PG 10 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA AX0JB UT WOS:000346637600043 PM 25534981 ER PT J AU Wani, WY Boyer-Guittaut, M Dodson, M Chatham, J Darley-Usmar, V Zhang, JH AF Wani, Willayat Yousuf Boyer-Guittaut, Michael Dodson, Matthew Chatham, John Darley-Usmar, Victor Zhang, Jianhua TI Regulation of autophagy by protein post-translational modification SO LABORATORY INVESTIGATION LA English DT Review ID PARKIN-MEDIATED MITOPHAGY; O-GLCNAC MODIFICATION; E3 UBIQUITIN LIGASE; LINKED N-ACETYLGLUCOSAMINE; TRANSCRIPTION FACTOR NRF2; BECLIN 1; SELECTIVE AUTOPHAGY; CROSS-TALK; MITOCHONDRIAL DEPOLARIZATION; DAMAGED MITOCHONDRIA AB Autophagy is a lysosome-mediated intracellular protein degradation process that involves about 38 autophagy-related genes as well as key signaling pathways that sense cellular metabolic and redox status, and has an important role in quality control of macromolecules and organelles. As with other major cellular pathways, autophagy proteins are subjected to regulatory post-translational modification. Phosphorylation is so far the most intensively studied post-translational modification in the autophagy process, followed by ubiquitination and acetylation. An interesting and new area is also now emerging, which appears to complement these more traditional mechanisms, and includes O-GlcNAcylation and redox regulation at thiol residues. Identification of the full spectrum of post-translational modifications of autophagy proteins, and determination of their impact on autophagy will be crucial for a better understanding of autophagy regulation, its deficits in diseases, and how to exploit this process for disease therapies. C1 [Wani, Willayat Yousuf; Dodson, Matthew; Chatham, John; Darley-Usmar, Victor; Zhang, Jianhua] Univ Alabama Birmingham, Ctr Free Radical Biol, Birmingham, AL 35294 USA. [Wani, Willayat Yousuf; Dodson, Matthew; Chatham, John; Darley-Usmar, Victor; Zhang, Jianhua] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Boyer-Guittaut, Michael] Univ Franche Comte, Lab Biochim, EA3922, SFR IBCT FED4234, F-25030 Besancon, France. [Zhang, Jianhua] Birmingham VA Med Ctr, Dept Vet Affairs, Birmingham, AL USA. RP Zhang, JH (reprint author), Univ Alabama Birmingham, Dept Pathol, Biomed Res Bldg 2,901 19th St South, Birmingham, AL 35294 USA. EM zhanja@uab.edu OI Zhang, Jianhua/0000-0002-2128-9574 FU [HL101192]; [HL-110366]; [NIHR01-NS064090] FX This work was supported by HL101192, HL-110366 (JC), and NIHR01-NS064090 (JZ). NR 129 TC 23 Z9 24 U1 3 U2 42 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2015 VL 95 IS 1 BP 14 EP 25 DI 10.1038/labinvest.2014.131 PG 12 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA AX5QA UT WOS:000346980700002 PM 25365205 ER PT J AU Angus, D Herd, C Stone, C Stout, J Wieler, M Reilmann, R Ritchie, CW Dorsey, ER Helles, K Kayson, E Oakes, D Rosas, HD Vaughan, C Panegyres, PK Ames, D Goh, A Agarwal, P Churchyard, A Murathodizic, M Chua, P Germaine, D Lim, L Mack, H Loy, C Griffith, J Mitchell, P Corey-Bloom, J Gluhm, S Goldstein, J Levi, L Margolis, R Yoritomo, N Janicki, S Marder, K Clouse, R Singer, C Moore, H Padron, N Kostyk, S Daley, A Segro, V Kumar, R Anderson, K Drazinic, C Hennig, B Nance, M Molho, E Criswell, S LeDoux, MS Guyot, S Iannaccone, A Jennings, B Leavitt, BR Feigin, A Evans, S Wray, S Casaceli, C Orme, C Gao, S Watts, A Baker, K Labuschagne, I El-Dairi, M Fekrat, S Hersch, S Moscovitch-Lopatin, M Tanzi, R Targum, S AF Angus, D. Herd, C. Stone, C. Stout, J. Wieler, M. Reilmann, R. Ritchie, C. W. Dorsey, E. R. Helles, K. Kayson, E. Oakes, D. Rosas, H. D. Vaughan, C. Panegyres, P. K. Ames, D. Goh, A. Agarwal, P. Churchyard, A. Murathodizic, M. Chua, P. Germaine, D. Lim, L. Mack, H. Loy, C. Griffith, J. Mitchell, P. Corey-Bloom, J. Gluhm, S. Goldstein, J. Levi, L. Margolis, R. Yoritomo, N. Janicki, S. Marder, K. Clouse, R. Singer, C. Moore, H. Padron, N. Kostyk, S. Daley, A. Segro, V. Kumar, R. Anderson, K. Drazinic, C. Hennig, B. Nance, M. Molho, E. Criswell, S. LeDoux, M. S. Guyot, S. Iannaccone, A. Jennings, B. Leavitt, B. R. Feigin, A. Evans, S. Wray, S. Casaceli, C. Orme, C. Gao, S. Watts, A. Baker, K. Labuschagne, I. El-Dairi, M. Fekrat, S. Hersch, S. Moscovitch-Lopatin, M. Tanzi, R. Targum, S. CA Huntington Study Grp Reach2HD Inve TI Safety, tolerability, and efficacy of PBT2 in Huntington's disease: a phase 2, randomised, double-blind, placebo-controlled trial SO LANCET NEUROLOGY LA English DT Article ID COGNITIVE ASSESSMENT; RATING-SCALE; A-BETA; HD; POLYGLUTAMINE; SUICIDE; LATREPIRDINE; CONSISTENCY; CLIOQUINOL; TOXICITY AB Background PBT2 is a metal protein-attenuating compound that might reduce metal-induced aggregation of mutant huntingtin and has prolonged survival in a mouse model of Huntington's disease. We aimed to assess the safety, tolerability, and efficacy of PBT2 in patients with Huntington's disease. Methods In this 26-week, randomised, double-blind, placebo-controlled trial, adults (>= 25 years old) with early-stage to mid-stage Huntington's disease were randomly assigned (1:1:1) by a centralised interactive response system to once daily PBT2 250 mg, PBT2 100 mg, or placebo. Randomisation was stratified by site with a block size of three. Participants, carers, the steering committee, site investigators, study staff, and the study sponsor were masked to treatment assignment. Primary endpoints were safety and tolerability. The safety population consisted of all participants who were randomly assigned and had at least one dose of study drug. The principal secondary endpoint was cognition, measured by the change from baseline to week 26 in the main composite Z score of five cognitive tests (Category Fluency Test, Trail Making Test Part B, Map Search, Symbol Digit Modalities Test, and Stroop Word Reading Test) and scores on eight individual cognitive tests (the five aforementioned plus the Trail Making Test Part A, Montreal Cognitive Assessment, and the Speeded Tapping Test). The intention-to-treat population comprised participants who were randomly assigned and had at least one efficacy assessment after administration of study drug. This trial is registered with ClinicalTrials.gov, NCT01590888. Findings Between April 18, 2012, and Dec 14, 2012, 109 participants were randomly assigned to PBT2 250 mg (n=36), PBT2 100 mg (n=38), or placebo (n=35) at 19 research centres in Australia and the USA. 32 (89%) individuals on PBT2 250 mg, 38 (100%) on PBT2 100 mg, and 34 (97%) on placebo completed the study. Six serious adverse events (acute coronary syndrome, major depression, pneumonia, suicide attempt, viral infection, and worsening of Huntington's disease) occurred in five participants in the PBT2 250 mg group, three (fall with subdural haematoma, suicide attempt, and hospital admission for stabilisation of Huntington's disease) occurred in two participants in the PBT2 100 mg group, and one (increasing aggression) occurred in a participant in the placebo group. The site investigators deemed all, except the worsening of Huntington's disease, as unrelated to study drug. 32 (89%) participants on PBT2 250 mg, 30 (79%) on PBT2 100 mg, and 28 (80%) on placebo had at least one adverse event. Compared with placebo, neither PBT2 100 mg (least-squares mean 0.02, 95% CI-0.10 to 0.14; p=0.772) nor PBT2 250 mg (0.07, -0.05 to 0. 20; p=0. 240) significantly improved the main composite cognition Z score between baseline and 26 weeks. Compared with placebo, the Trail Making Test Part B score was improved between baseline and 26 weeks in the PBT2 250 mg group (17.65 s, 0.65-34.65; p=0. 042) but not in the 100 mg group (0. 79 s improvement, -15.75 to 17.32; p=0.925); neither dose significantly improved cognition on the other tests. Interpretation PBT2 was generally safe and well tolerated in patients with Huntington's disease. The potential benefit on executive function will need to be confirmed in a larger study. C1 [Angus, D.; Herd, C.; Stone, C.] Prana Biotechnol, Parkville, Vic, Australia. [Stout, J.; Baker, K.; Labuschagne, I.] Monash Univ, Melbourne, Vic 3004, Australia. [Wieler, M.] Univ Alberta, Edmonton, AB, Canada. [Reilmann, R.] Univ Munster, D-48149 Munster, Germany. [Ritchie, C. W.] Univ London Imperial Coll Sci Technol & Med, London, England. [Dorsey, E. R.; Helles, K.; Kayson, E.; Oakes, D.; Gao, S.; Watts, A.] Univ Rochester, Rochester, NY USA. [Rosas, H. D.; Hersch, S.; Moscovitch-Lopatin, M.] Massachusetts Gen Hosp, Charlestown, MA USA. [Vaughan, C.] Med Univ S Carolina, Charleston, SC 29425 USA. [Panegyres, P. K.] Neurodegenerat Disorders Res, Perth, WA, Australia. [Ames, D.; Goh, A.] Univ Melbourne, Melbourne, Vic 3010, Australia. [Agarwal, P.] Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA. [Churchyard, A.; Murathodizic, M.] Monash Univ, Clayton, Vic, Australia. [Chua, P.; Germaine, D.; Lim, L.; Mack, H.] Royal Melbourne Hosp, Parkville, Vic 3050, Australia. [Loy, C.; Griffith, J.; Mitchell, P.] Westmead Hosp, Westmead, NSW 2145, Australia. [Corey-Bloom, J.; Gluhm, S.; Goldstein, J.; Levi, L.] Univ Calif San Diego, San Diego, CA 92103 USA. [Margolis, R.; Yoritomo, N.] Johns Hopkins Univ, Baltimore, MD USA. [Janicki, S.; Marder, K.; Clouse, R.] Columbia Univ, Med Ctr, New York, NY USA. [Singer, C.; Moore, H.; Padron, N.] Univ Miami, Miami, FL USA. [Kostyk, S.; Daley, A.] Ohio State Univ, Columbus, OH 43210 USA. [Segro, V.; Kumar, R.] Colorado Neurol Inst, Rocky Mt Movement Disorders Ctr, Englewood, CO USA. [Anderson, K.] Univ Maryland, Baltimore, MD 21201 USA. [Drazinic, C.; Hennig, B.] UConn Hlth, Farmington, CT USA. [Nance, M.] Struthers Parkinsons Ctr, Golden Valley, MN USA. [Molho, E.] Albany Med Coll, Albany, NY 12208 USA. [Criswell, S.] Washington Univ, St Louis, MO USA. [LeDoux, M. S.; Guyot, S.; Iannaccone, A.; Jennings, B.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Leavitt, B. R.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Feigin, A.] Feinstein Inst Med Res, Manhasset, NY USA. [Evans, S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Wray, S.] Massachusetts Gen Hosp, Charlestown, MA USA. [Casaceli, C.; Orme, C.] Univ Rochester, Clin Trials Coordinat Ctr, Rochester, NY USA. [El-Dairi, M.; Fekrat, S.] Duke Univ, Sch Med, Durham, NC USA. [Tanzi, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Targum, S.] Clintara, Boston, MA USA. RP Dorsey, ER (reprint author), Univ Rochester, Med Ctr, Rochester, NY 14642 USA. EM ray.dorsey@chet.rochester.edu RI Angus, Derek/E-9671-2012; OI Goh, Anita/0000-0003-0159-5926 FU Prana Biotechnology Limited FX Prana Biotechnology Limited. NR 32 TC 10 Z9 11 U1 6 U2 25 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 EI 1474-4465 J9 LANCET NEUROL JI Lancet Neurol. PD JAN PY 2015 VL 14 IS 1 BP 39 EP 47 DI 10.1016/S1474-4422(14)70262-5 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA AX4DZ UT WOS:000346885300024 ER PT J AU Ferrari, MD Klever, RR Terwindt, GM Ayata, C van den Maagdenberg, AMJM AF Ferrari, Michel D. Klever, Roselin R. Terwindt, Gisela M. Ayata, Cenk van den Maagdenberg, Arn M. J. M. TI Migraine pathophysiology: lessons from mouse models and human genetics SO LANCET NEUROLOGY LA English DT Review ID FAMILIAL HEMIPLEGIC MIGRAINE; CORTICAL SPREADING DEPRESSION; GENOME-WIDE ASSOCIATION; CA(V)2.1 CALCIUM-CHANNELS; PROTEIN-MEDIATED INHIBITION; DELAYED CEREBRAL EDEMA; TENSION-TYPE HEADACHE; SINGLE-FIBER EMG; KNOCK-IN MICE; MUTANT MICE AB Migraine is a common, disabling, and undertreated episodic brain disorder that is more common in women than in men. Unbiased genome-wide association studies have identified 13 migraine-associated variants pointing at genes that duster in pathways for glutamatergic neurotransmission, synaptic function, pain sensing, metalloproteinases, and the vasculature. The individual pathogenetic contribution of each gene variant is difficult to assess because of small effect sizes and complex interactions. Six genes with large effect sizes were identified in patients with rare monogenic migraine syndromes, in which hemiplegic migraine and non-hemiplegic migraine with or without aura are part of a wider clinical spectrum. Transgenic mouse models with human monogenic-migraine-syndrome gene mutations showed migraine-like features, increased glutamatergic neurotransmission, cerebral hyperexcitability, and enhanced susceptibility to cortical spreading depression, which is the electrophysiological correlate of aura and a putative trigger for migraine. Enhanced susceptibility to cortical spreading depression increased sensitivity to focal cerebral ischaemia, and blocking of cortical spreading depression improved stroke outcome in these mice. Changes in female hormone levels in these mice modulated cortical spreading depression susceptibility in much the same way that hormonal fluctuations affect migraine activity in patients. These findings confirm the multifactorial basis of migraine and might allow new prophylactic options to be developed, not only for migraine but potentially also for migraine-comorbid disorders such as epilepsy, depression, and stroke. C1 [Ferrari, Michel D.; Terwindt, Gisela M.; van den Maagdenberg, Arn M. J. M.] Leiden Univ, Med Ctr, Dept Neurol, NL-2300 RC Leiden, Netherlands. [Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Charlestown, MA USA. [Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Charlestown, MA USA. RP Ferrari, MD (reprint author), Leiden Univ, Med Ctr, Chair Leiden Ctr Translat Neurosci, Dept Neurol, Albinusdreef 2,POB 9600, NL-2300 RC Leiden, Netherlands. EM M.D.Ferrari@lumc.nl FU Netherlands Organisation for Scientific Research [918.56.602, 917.11.319]; European Community EUROHEADPAIN [602633]; NIMBL [241779]; BRAINPATH [612360]; Centre for Medical Systems Biology in the framework of the Netherlands Genomics Initiative FX Our work is supported by grants of the Netherlands Organisation for Scientific Research VICI (nr. 918.56.602 to MDF) and VIDI (nr. 917.11.319 to GMT); the European Community EUROHEADPAIN (nr. 602633) to MDF and AMJM vdM; NIMBL (nr. 241779) and BRAINPATH (nr. 612360) to AMJM vdM; and the Centre for Medical Systems Biology in the framework of the Netherlands Genomics Initiative) to AMJM vdM. This Review is dedicated to the memory of our PhD student and colleague Dr Esther Kors, who died on Jan 8, 2014. NR 161 TC 53 Z9 55 U1 12 U2 52 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 EI 1474-4465 J9 LANCET NEUROL JI Lancet Neurol. PD JAN PY 2015 VL 14 IS 1 BP 65 EP 80 PG 16 WC Clinical Neurology SC Neurosciences & Neurology GA AX4DZ UT WOS:000346885300027 PM 25496898 ER PT J AU Ahmadi, SF Baradaran, HR Ahmadi, E AF Ahmadi, Seyed-Foad Baradaran, Hamid R. Ahmadi, Emad TI Effectiveness of teaching evidence-based medicine to undergraduate medical students: A BEME systematic review SO MEDICAL TEACHER LA English DT Review ID RANDOMIZED-CONTROLLED-TRIAL; CRITICAL-APPRAISAL; CLINICAL QUESTIONS; SEARCHING SKILLS; EDUCATION; CURRICULUM; KNOWLEDGE; INSTRUCTION; COMPETENCE; INTERVENTION AB Background: Despite the widespread teaching of evidence-based medicine (EBM) to medical students, the relevant literature has not been synthesized appropriately as to its value and effectiveness. Aim: To systematically review the literature regarding the impact of teaching EBM to medical students on their EBM knowledge, attitudes, skills and behaviors. Methods: MEDLINE, SCOPUS, Web of science, ERIC, CINAHL and Current Controlled Trials up to May 2011 were searched; backward and forward reference checking of included and relevant studies was also carried out. Two investigators independently extracted data and assessed the quality of the studies. Results: 10,111 potential studies were initially found, of which 27 were included in the review. Six studies examined the effect of clinically integrated methods, of which five had a low quality and the other one used no validated assessment tool. Twelve studies evaluated the effects of seminars, workshops and short courses, of which 11 had a low quality and the other one lacked a validated assessment tool. Six studies examined e-learning, of which five having a high or acceptable quality reported e-learning to be as effective as traditional teaching in improving knowledge, attitudes and skills. One robust study found problem-based learning less effective compared to usual teaching. Two studies with high or moderate quality linked multicomponent interventions to improved knowledge and attitudes. No included study assessed the long-term effects of the teaching of EBM. Conclusions: Our findings indicated that some EBM teaching strategies have the potential to improve knowledge, attitudes and skills in undergraduate medical students, but the evidenced base does not demonstrate superiority of one method. There is no evidence demonstrating transfer to clinical practice. C1 [Ahmadi, Seyed-Foad; Baradaran, Hamid R.] Iran Univ Med Sci, Ctr Educ Res Med Sci, Tehran 1449614535, Iran. [Ahmadi, Seyed-Foad] Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA. [Ahmadi, Emad] Univ Tehran Med Sci, Digest Dis Res Inst, Tehran, Iran. [Ahmadi, Emad] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Baradaran, HR (reprint author), Iran Univ Med Sci, Ctr Educ Res Med Sci, Tehran 1449614535, Iran. EM baradaran.hr@iums.ac.ir RI Baradaran, Hamid Reza/C-1556-2017 OI Baradaran, Hamid Reza/0000-0002-5070-5864 NR 60 TC 3 Z9 3 U1 2 U2 25 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0142-159X EI 1466-187X J9 MED TEACH JI Med. Teach. PD JAN PY 2015 VL 37 IS 1 BP 21 EP 30 DI 10.3109/0142159X.2014.971724 PG 10 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA AX0LF UT WOS:000346643200003 PM 25401408 ER PT J AU Brown, DN AF Brown, Douglas N. TI Laparoscopic or vaginal hysterectomy? SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID UNITED-STATES; OUTCOMES; VOLUME C1 Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Ctr Minimally Invas Gynecol Surg, Boston, MA 02114 USA. RP Brown, DN (reprint author), Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Ctr Minimally Invas Gynecol Surg, Boston, MA 02114 USA. NR 19 TC 1 Z9 1 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JAN PY 2015 VL 22 IS 1 BP 9 EP 11 DI 10.1097/gme.0000000000000388 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AX2GC UT WOS:000346760500004 PM 25490114 ER PT J AU Pinkerton, JV Joffe, H Kazempour, K Mekonnen, H Bhaskar, S Lippman, J AF Pinkerton, JoAnn V. Joffe, Hadine Kazempour, Kazem Mekonnen, Hana Bhaskar, Sailaja Lippman, Joel TI Low-dose paroxetine (7.5 mg) improves sleep in women with vasomotor symptoms associated with menopause SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Hot flashes; Menopause; Nighttime awakening; Paroxetine 7.5 mg; Sleep duration; Vasomotor symptoms ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; HOT FLASHES; POSTMENOPAUSAL WOMEN; BREAST-CANCER; ANTIDEPRESSANT; DISTURBANCE; PERIMENOPAUSAL; GABAPENTIN; TRANSITION AB Objective: Sleep disturbances are common among women in midlife; prevalence increases among perimenopausal/postmenopausal women with vasomotor symptoms. Paroxetine 7.5 mg is the only nonhormonal treatment that has been approved in the United States for moderate to severe vasomotor symptoms associated with menopause. In two pivotal phase 3 studies evaluating its efficacy and safety, improvements in sleep disturbances were also prospectively evaluated. Methods: Postmenopausal women with moderate to severe vasomotor symptoms were randomly assigned to paroxetine 7.5 mg (n = 591) or placebo (n = 593) once daily for 12 weeks (both studies) or 24 weeks (24-wk study). Predefined assessments on weeks 4, 12, and 24 included number of nighttime awakenings attributed to vasomotor symptoms, sleep-onset latency, sleep duration, and sleep-related adverse events. The two studies' data for weeks 1 to 12 were pooled. Results: At baseline, participants reported a mean of 3.6 awakenings/night attributed to vasomotor symptoms. Nighttime awakenings attributed to vasomotor symptoms were significantly reduced within 4 weeks of initiating paroxetine 7.5 mg treatment (39% reduction vs 28% for placebo; P = 0.0049), and reductions were sustained through 12 or 24 weeks of treatment. Paroxetine 7.5 mg treatment also significantly increased nighttime sleep duration (week 4, + 31 vs + 16 min for placebo; P = 0.0075), but no significant between-group differences in sleep-onset latency or sleep-related adverse events such as sedation were observed. Conclusions: In postmenopausal women treated for menopausal vasomotor symptoms, paroxetine 7.5 mg significantly reduces the number of nighttime awakenings attributed to vasomotor symptoms and increases sleep duration without differentially affecting sleep-onset latency or sedation. C1 [Pinkerton, JoAnn V.] Univ Virginia, Div Midlife Hlth, Charlottesville, VA 22908 USA. [Joffe, Hadine] Brigham & Womens Hosp, Boston, MA 02115 USA. [Joffe, Hadine] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kazempour, Kazem; Mekonnen, Hana] Amarex Clin Res, Germantown, MD USA. [Bhaskar, Sailaja; Lippman, Joel] Noven Pharmaceut Inc, New York, NY USA. RP Pinkerton, JV (reprint author), Univ Virginia, Midlife Hlth Ctr, Box 801104, Charlottesville, VA 22908 USA. EM Jvp9u@virginia.edu NR 50 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JAN PY 2015 VL 22 IS 1 BP 50 EP 58 DI 10.1097/gme.0000000000000311 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AX2GC UT WOS:000346760500011 PM 25137243 ER PT J AU Moisan, A Lee, YK Zhang, JD Hudak, CS Meyer, CA Prummer, M Zoffmann, S Truong, HH Ebeling, M Kiialainen, A Gerard, R Xia, F Schinzel, RT Amrein, KE Cowan, CA AF Moisan, Annie Lee, Youn-Kyoung Zhang, Jitao David Hudak, Carolyn S. Meyer, Claas A. Prummer, Michael Zoffmann, Sannah Truong, Hoa Hue Ebeling, Martin Kiialainen, Anna Gerard, Regine Xia, Fang Schinzel, Robert T. Amrein, Kurt E. Cowan, Chad A. TI White-to-brown metabolic conversion of human adipocytes by JAK inhibition SO NATURE CELL BIOLOGY LA English DT Article ID UNCOUPLING PROTEIN GENE; ADIPOSE-TISSUE; THYROID-HORMONE; CELLULAR PLASTICITY; TYROSINE KINASE; FAT; ACTIVATION; DISCOVERY; OBESITY; MOUSE AB The rising incidence of obesity and related disorders such as diabetes and heart disease has focused considerable attention on the discovery of new therapeutics. One promising approach has been to increase the number or activity of brown-like adipocytes in white adipose depots, as this has been shown to prevent diet-induced obesity and reduce the incidence and severity of type 2 diabetes. Thus, the conversion of fat-storing cells into metabolically active thermogenic cells has become an appealing therapeutic strategy to combat obesity. Here, we report a screening platform for the identification of small molecules capable of promoting a white-to-brown metabolic conversion in human adipocytes. We identified two inhibitors of Janus kinase (JAK) activity with no precedent in adipose tissue biology that stably confer brown-like metabolic activity to white adipocytes. Importantly, these metabolically converted adipocytes exhibit elevated UCP1 expression and increased mitochondrial activity. We further found that repression of interferon signalling and activation of hedgehog signalling in JAK-inactivated adipocytes contributes to the metabolic conversion observed in these cells. Our findings highlight a previously unknown role for the JAK-STAT pathway in the control of adipocyte function and establish a platform to identify compounds for the treatment of obesity. C1 [Moisan, Annie; Zhang, Jitao David; Meyer, Claas A.; Prummer, Michael; Zoffmann, Sannah; Truong, Hoa Hue; Ebeling, Martin; Kiialainen, Anna; Gerard, Regine; Amrein, Kurt E.] Roche Innovat Ctr Basel, Roche Pharma Res & Early Dev, CH-4070 Basel, Switzerland. [Lee, Youn-Kyoung; Hudak, Carolyn S.; Xia, Fang; Schinzel, Robert T.; Cowan, Chad A.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Lee, Youn-Kyoung; Hudak, Carolyn S.; Xia, Fang; Schinzel, Robert T.; Cowan, Chad A.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Lee, Youn-Kyoung; Hudak, Carolyn S.; Xia, Fang; Schinzel, Robert T.; Cowan, Chad A.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. RP Moisan, A (reprint author), Roche Innovat Ctr Basel, Roche Pharma Res & Early Dev, 124 Grenzacherstr, CH-4070 Basel, Switzerland. EM annie.moisan@roche.com; chad_cowan@harvard.edu RI Prummer, Michael/G-6464-2011 OI Prummer, Michael/0000-0001-9896-3929 FU Roche Postdoctoral Fellowship (RPF) program; F.Hoffmann-La Roche; United States Institutes of Health (NIH) [R01DK095384, R01DK097768]; Harvard University FX The authors thank I. Clausen, M. Kapps, R. Schmucki and A. Schuler for technical support, K. Christensen and M. Graf for stem cell support, L. Badi for preliminary data analysis, C. Solier, A. Schell-Steven and T. Bergauer for experimental planning and M. Pawlak (Natural and Medical Sciences Institute at the University of Tubingen) for RPPA analyses. A.M. was supported by the Roche Postdoctoral Fellowship (RPF) program (2011-2013). This research was supported in part by F.Hoffmann-La Roche; grant R01DK095384 (C.A.C. and Y.K.L.) and R01DK097768 (C.A.C.) from the United States Institutes of Health (NIH); and Harvard University. NR 35 TC 34 Z9 39 U1 4 U2 33 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 EI 1476-4679 J9 NAT CELL BIOL JI Nat. Cell Biol. PD JAN PY 2015 VL 17 IS 1 BP 57 EP + DI 10.1038/ncb3075 PG 24 WC Cell Biology SC Cell Biology GA AX3ET UT WOS:000346823900008 PM 25487280 ER PT J AU Thorpe, LM Yuzugullu, H Zhao, JJ AF Thorpe, Lauren M. Yuzugullu, Haluk Zhao, Jean J. TI PI3K in cancer: divergent roles of isoforms, modes of activation and therapeutic targeting SO NATURE REVIEWS CANCER LA English DT Review ID G-BETA-GAMMA; PTEN TUMOR-SUPPRESSOR; PHOSPHOINOSITIDE 3-KINASE P110-DELTA; PROTEIN-COUPLED RECEPTORS; REGULATORY SUBUNIT P85-ALPHA; P110-BETA CATALYTIC SUBUNIT; MAMMARY EPITHELIAL-CELLS; NEGATIVE BREAST-CANCER; 4-PHOSPHATASE TYPE-II; PHOSPHATIDYLINOSITOL 3-KINASE AB Phosphatidylinositol 3-kinases (PI3Ks) are crucial coordinators of intracellular signalling in response to extracellular stimuli. Hyperactivation of PI3K signalling cascades is one of the most common events in human cancers. In this Review, we discuss recent advances in our knowledge of the roles of specific PI3K isoforms in normal and oncogenic signalling, the different ways in which PI3K can be upregulated, and the current state and future potential of targeting this pathway in the clinic. C1 [Thorpe, Lauren M.; Yuzugullu, Haluk; Zhao, Jean J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Thorpe, Lauren M.; Yuzugullu, Haluk; Zhao, Jean J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Thorpe, Lauren M.] Harvard Univ, Sch Med, Program Virol, Boston, MA 02115 USA. RP Zhao, JJ (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. EM jean_zhao@dfci.harvard.edu OI Thorpe, Lauren/0000-0002-5302-9136 FU US National Institutes of Health (NIH) [CA172461-01, P50 CA168504-01A1, P50 CA165962-01A1]; Stand Up to Cancer Dream Team Translational Research grant [SU2C-AACR-DT0209] FX The authors thank T. M. Roberts for critical reading of the manuscript, T. M. Roberts and L. C. Cantley for discussions, and N. Rosen and J. A. Engelman for sharing unpublished observations. They also thank the reviewers for their suggestions and apologize to the many colleagues whose work they were unable cite owing to space limitations. Research in the laboratory of J. J. Z. is supported by the US National Institutes of Health (NIH) grants CA172461-01, P50 CA168504-01A1, P50 CA165962-01A1 and the Stand Up to Cancer Dream Team Translational Research grant SU2C-AACR-DT0209. NR 204 TC 125 Z9 130 U1 18 U2 67 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X EI 1474-1768 J9 NAT REV CANCER JI Nat. Rev. Cancer PD JAN PY 2015 VL 15 IS 1 BP 7 EP 24 DI 10.1038/nrc3860 PG 18 WC Oncology SC Oncology GA AX3IL UT WOS:000346833100006 PM 25533673 ER PT J AU Dimopoulos, MA Richardson, PG Moreau, P Anderson, KC AF Dimopoulos, Meletios A. Richardson, Paul G. Moreau, Philippe Anderson, Kenneth C. TI Current treatment landscape for relapsed and/or refractory multiple myeloma SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Review ID SINGLE-AGENT CARFILZOMIB; LENALIDOMIDE PLUS DEXAMETHASONE; PEGYLATED LIPOSOMAL DOXORUBICIN; LOW-DOSE DEXAMETHASONE; STEM-CELL TRANSPLANTATION; PREVIOUSLY TREATED PATIENTS; HIGH-RISK CYTOGENETICS; OPEN-LABEL; SALVAGE THERAPY; HERPES-ZOSTER AB Recent developments in the treatment of multiple myeloma have led to improvements in response rates and to increased survival; however, relapse is inevitable in almost all patients. Recurrence of myeloma is typically more aggressive with each relapse, leading to the development of treatment-refractory disease, which is associated with a shorter survival. Several phase II and III trials have demonstrated the efficacy of recently approved agents in the setting of relapsed and/or refractory multiple myeloma, including immunomodulatory agents, such as lenalidomide and pomalidomide, and proteasome inhibitors, such as bortezomib and carfilzomib. Currently, however, there is no standard treatment for patients with relapsed and/or refractory disease. This Review discusses the current treatment landscape for patients with relapsed and/or refractory multiple myeloma and highlights disease-related and patient-related factors-such as pre-existing comorbidities or toxicities-that are important considerations for clinicians when selecting an appropriate treatment regimen. C1 [Dimopoulos, Meletios A.] Univ Athens, Sch Med, Dept Clin Therapeut, Athens 11528, Greece. [Richardson, Paul G.; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Moreau, Philippe] Univ Hosp Hotel Dieu, Dept Haematol, F-44093 Nantes 01, France. RP Dimopoulos, MA (reprint author), Univ Athens, Sch Med, Dept Clin Therapeut, 80 Vas Sofias Ave, Athens 11528, Greece. EM mdimop@med.uoa.gr RI richard, chrystelle/K-8595-2015 FU Onyx Pharmaceuticals, Inc. FX The authors gratefully acknowledge editorial assistance provided by BlueMomentum (a division of KnowledgePoint360 Group, San Bruno, CA, and funded by Onyx Pharmaceuticals, Inc.). The authors also gratefully acknowledge the support of Michelle Maglio, administrative assistant, of the Dana Farber Cancer Institute in the preparation of this manuscript. NR 128 TC 41 Z9 41 U1 5 U2 26 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 EI 1759-4782 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD JAN PY 2015 VL 12 IS 1 BP 42 EP 54 DI 10.1038/nrclinonc.2014.200 PG 13 WC Oncology SC Oncology GA AX3IW UT WOS:000346834100009 PM 25421279 ER PT J AU Kim, H Abla, AA Nelson, J McCulloch, CE Bervini, D Morgan, MK Stapleton, C Walcott, BP Ogilvy, CS Spetzler, RF Lawton, MT Alleyne, CH Zipfel, GJ Howard, BM Barrow, DL AF Kim, Helen Abla, Adib A. Nelson, Jeffrey McCulloch, Charles E. Bervini, David Morgan, Michael K. Stapleton, Christopher Walcott, Brian P. Ogilvy, Christopher S. Spetzler, Robert F. Lawton, Michael T. Alleyne, Cargill H., Jr. Zipfel, Gregory J. Howard, Brian M. Barrow, Daniel L. TI Validation of the Supplemented Spetzler-Martin Grading System for Brain Arteriovenous Malformations in a Multicenter Cohort of 1009 Surgical Patients SO NEUROSURGERY LA English DT Article DE Arteriovenous malformation; Microsurgery; Patient selection; Risk prediction; Spetzler-Martin grading system; Supplementary grading system ID SELECTING PATIENTS; SURGERY; CLASSIFICATION; SCALE; MODEL AB BACKGROUND: The supplementary grading system for brain arteriovenous malformations (AVMs) was introduced in 2010 as a tool for improving preoperative risk prediction and selecting surgical patients. OBJECTIVE: To demonstrate in this multicenter validation study that supplemented Spetzler-Martin (SM-Supp) grades have greater predictive accuracy than Spetzler-Martin (SM) grades alone. METHODS: Data collected from 1009 AVM patients who underwent AVM resection were used to compare the predictive powers of SM and SM-Supp grades. Patients included the original 300 University of California, San Francisco patients plus those treated thereafter (n = 117) and an additional 592 patients from 3 other centers. RESULTS: In the combined cohort, the SM-Supp system performed better than SM system alone: area under the receiver-operating characteristics curve (AUROC) = 0.75 (95% confidence interval, 0.71-0.78) for SM-Supp and AUROC = 0.69 (95% confidence interval, 0.65-0.73) for SM (P < .001). Stratified analysis fitting models within 3 different follow-up groupings (< 6 months, 6 months-2 years, and > 2 years) demonstrated that the SM-Supp system performed better than SM system for both medium (AUROC = 0.71 vs 0.62; P =.003) and long (AUROC = 0.69 vs 0.58; P = .001) follow-up. Patients with SM-Supp grades <= 6 had acceptably low surgical risks (0%-24%), with a significant increase in risk for grades >= 6 (39%-63%). CONCLUSION: This study validates the predictive accuracy of the SM-Supp system in a multicenter cohort. An SM-Supp grade of 6 is a cutoff or boundary for AVM operability. Supplemented grading is currently the best method of estimating neurological outcomes after AVM surgery, and we recommend it as a starting point in the evaluation of AVM operability. C1 [Kim, Helen; Nelson, Jeffrey; Lawton, Michael T.] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. [Kim, Helen; McCulloch, Charles E.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Kim, Helen; Nelson, Jeffrey; McCulloch, Charles E.; Lawton, Michael T.] Univ Calif San Francisco, Cerebrovasc Res Ctr, San Francisco, CA 94143 USA. [Lawton, Michael T.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Bervini, David; Morgan, Michael K.] Macquarie Univ, Dept Neurol Surg, Sydney, NSW 2109, Australia. [Stapleton, Christopher; Walcott, Brian P.; Ogilvy, Christopher S.] Massachusetts Gen Hosp, Dept Neurol Surg, Boston, MA 02114 USA. [Spetzler, Robert F.] Barrow Neurol Inst, Div Neurol Surg, Phoenix, AZ 85013 USA. RP Lawton, MT (reprint author), Univ Calif San Francisco, Dept Neurol Surg, 505 Parnassus Ave,M780,Box 0112, San Francisco, CA 94143 USA. EM lawtonm@neurosurg.ucsf.edu OI Morgan, Michael/0000-0002-9841-9461 FU National Institutes of Health [R01 NS034949] FX This work was funded in part by a grant from the National Institutes of Health (R01 NS034949; principal investigator, Dr Kim). The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. NR 19 TC 33 Z9 34 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X EI 1524-4040 J9 NEUROSURGERY JI Neurosurgery PD JAN PY 2015 VL 76 IS 1 BP 25 EP 33 DI 10.1227/NEU.0000000000000556 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA AW9UC UT WOS:000346602000010 PM 25251197 ER PT J AU Tanpowpong, P Broder-Fingert, S Katz, AJ Camargo, CA AF Tanpowpong, Pornthep Broder-Fingert, Sarabeth Katz, Aubrey J. Camargo, Carlos A., Jr. TI Predictors of dietary gluten avoidance in adults without a prior diagnosis of celiac disease SO NUTRITION LA English DT Article DE Lactose; Allergy; Diarrhea; Serology; Predictors ID CHILDREN; IMPLEMENTATION; POPULATION; PREVALENCE; NUTRITION; HEALTH AB Objective: Prior studies have shown that dietary gluten avoidance (DGA) is relatively common in children without previously diagnosed celiac disease (CD), and several clinical predictors of DGA have been found. However, available data on predictors of DGA in adults without diagnosed CD are limited. The aim of this study was to determine the independent predictors of DGA in this population. Methods: We performed a structured medical record review of 376 patients, ages >= 20 y, who had never been formally diagnosed with CD, presenting for an initial CD evaluation (ICD-9-CM 579.0) between January 2000 and December 2010 at two large Boston teaching hospitals. We collected data including demographic characteristics, medical history, history of CD serology before referral, and self-reported DGA. Predictors of DGA were determined using multivariable logistic regression. Results: Mean age was 47 (SD = 17) years. We found that 41 patients (10.9%; 95% confidence interval [CI], 7.9-14.5) had avoided gluten at some time in their lives. Most patients had subjective abdominal complaints or bowel movement changes. History of CD seropositivity before referral was noted in 14%. Independent predictors of DGA (P < 0.05) were lactose intolerance (odds ratio [OR], 2.8; 95% CI, 1.1-7.5), food allergy (OR, 3.8; 95% CI, 1.04-13.7), and history of positive serology of less-specific CD markers before the referral (OR, 3.2; 95% CI, 1.3-7.9). Conclusions: Gluten avoidance is common in a clinic population of adults without prior CD diagnosis. The recognized predictors suggest that DGA may associate with conditions presenting with nonspecific gastrointestinal complaints and perhaps with the perceived benefits of DGA among patients with prior history of positive CD serology. (C) 2015 Elsevier Inc. All rights reserved. C1 [Tanpowpong, Pornthep] Mahidol Univ, Ramathibodi Hosp, Fac Med, Div Gastroenterol,Dept Pediat, Bangkok 10400, Thailand. [Broder-Fingert, Sarabeth] Massachusetts Gen Hosp Children, Dept Pediat, Boston, MA USA. [Broder-Fingert, Sarabeth; Katz, Aubrey J.; Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Boston, MA USA. [Katz, Aubrey J.] Massachusetts Gen Hosp Children, Div Pediat Gastroenterol, Boston, MA USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Tanpowpong, P (reprint author), Mahidol Univ, Ramathibodi Hosp, Fac Med, Div Gastroenterol,Dept Pediat, Bangkok 10400, Thailand. EM Tuinoi1@gmail.com OI Broder-Fingert, Sarabeth/0000-0002-0932-4461 NR 15 TC 1 Z9 1 U1 2 U2 24 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-9007 EI 1873-1244 J9 NUTRITION JI Nutrition PD JAN PY 2015 VL 31 IS 1 BP 236 EP 238 DI 10.1016/j.nut.2014.07.001 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AX1CJ UT WOS:000346685600035 PM 25441597 ER PT J AU Sonneville, KR Long, MW Rifas-Shiman, SL Kleinman, K Gillman, MW Taveras, EM AF Sonneville, Kendrin R. Long, Michael W. Rifas-Shiman, Sheryl L. Kleinman, Ken Gillman, Matthew W. Taveras, Elsie M. TI Juice and Water Intake in Infancy and Later Beverage Intake and Adiposity: Could Juice be a Gateway Drink? SO OBESITY LA English DT Article ID SUGAR-SWEETENED BEVERAGES; PRESCHOOL-AGED CHILDREN; BODY-MASS INDEX; CHILDHOOD OBESITY; WEIGHT STATUS; FRUIT JUICE; RACIAL/ETHNIC DISPARITIES; VEGETABLE INTAKE; UNITED-STATES; ENERGY-INTAKE AB ObjectivesTo examine the tracking and significance of beverage consumption in infancy and childhood. MethodsAmong 1163 children in Project Viva, we examined associations of fruit juice and water intake at 1 year (0 oz, 1-7 oz [small], 8-15 oz [medium], and 16 oz [large]) with juice and sugar-sweetened beverage (SSB) intake and BMI z-score during early (median 3.1 years) and mid-childhood (median 7.7 years). ResultsIn covariate adjusted models, juice intake at 1 year was associated with greater juice and SSB intake during early and mid-childhood and also greater adiposity. Children who drank medium and large amounts of juice at 1 year had higher BMI z-scores during both early (medium: =0.16 [95% CI=0.01-0.32]; large: =0.28 [95% CI=0.01-0.56]) and mid-childhood (medium: =0.23 [95% CI=0.07-0.39]; large: =0.36 [95% CI=0.08-0.64]). After covariate adjustment, associations between water intake at 1 year and beverage intake and adiposity later in childhood were null. ConclusionsHigher juice intake at 1 year was associated with higher juice intake, SSB intake, and BMI z-score during early and mid-childhood. Assessing juice intake during infancy could provide clinicians with important data regarding future unhealthy beverage habits and excess adiposity during childhood. C1 [Sonneville, Kendrin R.] Boston Childrens Hosp, Div Adolescent Med, Boston, MA 02115 USA. [Sonneville, Kendrin R.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Sonneville, Kendrin R.] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. [Long, Michael W.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Rifas-Shiman, Sheryl L.; Kleinman, Ken; Gillman, Matthew W.; Taveras, Elsie M.] Harvard Univ, Sch Med, Dept Populat Med, Obes Prevent Program, Boston, MA USA. [Rifas-Shiman, Sheryl L.; Kleinman, Ken; Gillman, Matthew W.; Taveras, Elsie M.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Gillman, Matthew W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Taveras, Elsie M.] Massachusetts Gen Hosp, Div Gen Pediat, Boston, MA 02114 USA. RP Sonneville, KR (reprint author), Boston Childrens Hosp, Div Adolescent Med, Boston, MA 02115 USA. EM ksonnevi@umich.edu FU Centers for Disease Control and Prevention; U.S. National Institutes of Health [HD 34568, HL 64925, HL 68041]; Harvard Medical School; Harvard Pilgrim Health Care Foundation FX This research was supported by grants from the Centers for Disease Control and Prevention and U.S. National Institutes of Health (HD 34568, HL 64925, HL 68041) and by Harvard Medical School and the Harvard Pilgrim Health Care Foundation. NR 38 TC 8 Z9 8 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD JAN PY 2015 VL 23 IS 1 BP 170 EP 176 DI 10.1002/oby.20927 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA AX2JS UT WOS:000346770100028 PM 25328160 ER PT J AU Sayegh, RR Dohlman, CH Greenstein, SH Peli, E AF Sayegh, Rony R. Dohlman, Claes H. Greenstein, Scott H. Peli, Eli TI The Boston keratoprosthesis provides a wide depth of focus SO OPHTHALMIC AND PHYSIOLOGICAL OPTICS LA English DT Article DE depth of focus; keratoprosthesis; optics; refraction; through-focus ID VISUAL-ACUITY; HUMAN EYE; OF-FOCUS; DEFOCUS CURVES; ACCOMMODATION; PRESBYOPIA; DESIGN AB PurposeTo measure the through-focus curve for eyes implanted with a type 1 Boston keratoprosthesis (KPro) and compare it to that of pseudophakic controls with fixed pupil sizes. The results should assist in evaluating postoperative visual quality after surgery. They should also help to determine the necessary KPro inventories in terms of refractive power steps. MethodsAutorefraction and manifest refraction were performed on all eyes. The monocular through-focus acuity curve was plotted in reference to the best-corrected visual acuity by spectacle plane defocus ranging from +5.00 to -5.00dioptres in 0.50dioptre increments. These measurements were obtained on KPro-implanted eyes, pseudophakic eyes as controls, and on the same control eyes after fixing the pupil diameter to 3 and 2mm using black painted iris contact lenses. ResultsTen KPro eyes and five control eyes were included. Good agreement was noted between the subjective refractions and autorefraction in KPro eyes. The average through-focus curve for the control eyes was significantly steeper than that of the KPro curve, but became comparable after fixing the control pupil to 2 and 3mm. ConclusionThe KPro's wide depth-of-focus makes the visual acuity less dependent on an exact refractive correction at distance and explains the pseudoaccomodation' experienced by these patients. This is primarily due to the small pupil diameter of the KPro. The current manufacturing steps in 0.50 dioptre increments appears to be sufficient. C1 [Sayegh, Rony R.] Case Western Reserve Univ, Univ Hosp Eye Inst, Univ Hosp Case Med Ctr, Sch Med, Cleveland, OH 44106 USA. [Sayegh, Rony R.; Dohlman, Claes H.; Greenstein, Scott H.; Peli, Eli] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA 02163 USA. RP Peli, E (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA 02163 USA. EM eli_peli@meei.harvard.edu FU Keratoprosthesis Fund, Massachusetts Eye and Ear Infirmary; NIH [R01EY12890] FX The study was supported in part by the Keratoprosthesis Fund, Massachusetts Eye and Ear Infirmary and by NIH grant # R01EY12890 (EP). We thank P. Matthew Bronstad PhD for statistical help. NR 22 TC 0 Z9 0 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0275-5408 EI 1475-1313 J9 OPHTHAL PHYSL OPT JI Ophthalmic Physiol. Opt. PD JAN PY 2015 VL 35 IS 1 BP 39 EP 44 DI 10.1111/opo.12181 PG 6 WC Ophthalmology SC Ophthalmology GA AX2JO UT WOS:000346769700006 PM 25424372 ER PT J AU Farrell, MJ Shin, JI Smith, LJ Mauck, RL AF Farrell, M. J. Shin, J. I. Smith, L. J. Mauck, R. L. TI Functional consequences of glucose and oxygen deprivation on engineered mesenchymal stem cell-based cartilage constructs SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE Mesenchymal stem cells; Chondrogenesis; Three-dimensional culture; Mechanical properties; Glucose; Hypoxia ID BONE-MARROW; CHONDROGENIC DIFFERENTIATION; MECHANICAL-PROPERTIES; OSTEOGENIC DIFFERENTIATION; CLONAL HETEROGENEITY; ARTICULAR-CARTILAGE; STROMAL CELLS; AGAROSE GELS; HYPOXIA; CULTURE AB Objective: Tissue engineering approaches for cartilage repair have focused on the use of mesenchymal stem cells (MSCs). For clinical success, MSCs must survive and produce extracellular matrix in the physiological context of the synovial joint, where low nutrient conditions engendered by avascularity, nutrient utilization, and waste production prevail. This study sought to delineate the role of microenvironmental stressors on MSC viability and functional capacity in three dimensional (3D) culture. Design: We evaluated the impact of glucose and oxygen deprivation on the functional maturation of 3D MSC-laden agarose constructs. Since MSC isolation procedures result in a heterogeneous cell population, we also utilized micro-pellet culture to investigate whether clonal subpopulations respond to these microenvironmental stressors in a distinct fashion. Results: MSC health and the functional maturation of 3D constructs were compromised by both glucose and oxygen deprivation. Importantly, glucose deprivation severely limited viability, and so compromised the functional maturation of 3D constructs to the greatest extent. The observation that not all cells died suggested there exists heterogeneity in the response of MSC populations to metabolic stressors. Population heterogeneity was confirmed through a series of studies utilizing clonally derived subpopulations, with a spectrum of matrix production and cell survival observed under conditions of metabolic stress. Conclusions: Our findings show that glucose deprivation has a significant impact on functional maturation, and that some MSC subpopulations are more resilient to metabolic challenge than others. These findings suggest that pre-selection of subpopulations that are resilient to metabolic challenge may improve in vivo outcomes. (C) 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 [Farrell, M. J.; Shin, J. I.; Smith, L. J.; Mauck, R. L.] Univ Penn, McKay Orthopaed Res Lab, Dept Orthopaed Surg, Perelman Sch Med, Philadelphia, PA 19104 USA. [Farrell, M. J.; Mauck, R. L.] Univ Penn, Dept Bioengn, Sch Engn & Appl Sci, Philadelphia, PA 19104 USA. [Farrell, M. J.; Smith, L. J.; Mauck, R. L.] Philadelphia VA Med Ctr, Translat Musculoskeletal Res Ctr, Dept Vet Affairs, Philadelphia, PA 19104 USA. [Smith, L. J.] Univ Penn, Dept Neurosurg, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Mauck, RL (reprint author), Univ Penn, McKay Orthopaed Res Lab, 424 Stemmler Hall,36th St & Hamilton Walk, Philadelphia, PA 19104 USA. EM lemauck@mail.med.upenn.edu FU National Institutes of Health [R01 EB008722]; Department of Veterans' Affairs [I01 RX000700] FX This work was supported by the National Institutes of Health (R01 EB008722) and the Department of Veterans' Affairs (I01 RX000700). The authors would like to thank Joseph Chiaro and Deborah Gorth for technical assistance with hypoxic culture. The authors have no conflicts of interest to report that relate to this work. NR 50 TC 7 Z9 7 U1 2 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 EI 1522-9653 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD JAN PY 2015 VL 23 IS 1 BP 134 EP 142 DI 10.1016/j.joca.2014.09.012 PG 9 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA AX0OA UT WOS:000346650300018 PM 25241241 ER PT J AU Sanchez, A Rodriguez, D Cheng, JS McGovern, FJ Tabatabaei, S AF Sanchez, Alejandro Rodriguez, Dayron Cheng, Jed-Sian McGovern, Francis J. Tabatabaei, Shahin TI Prostato-symphyseal Fistula After Photoselective Vaporization of the Prostate: Case Series and Literature Review of a Rare Complication SO UROLOGY LA English DT Article ID GREENLIGHT LASER VAPORIZATION; TRANSURETHRAL RESECTION; OSTEITIS PUBIS; SINGLE-CENTER; HYPERPLASIA; THERAPY; EFFICACY; SAFETY; TRIAL; 180W AB OBJECTIVE To report our experience with the management of prostato-symphyseal fistula (PSF) after photoselective vaporization (PVP) or transurethral resection of the prostate (TURP) and review cases of this complication in published reports. MATERIALS AND METHODS We report the management of 3 patients with PSF after PVP at our institution. A total of 5 published cases of PSF after PVP or TURP were identified from the National Library of Medicine MEDLINE database. A total of 8 patients were reviewed. RESULTS Overall, the mean age was 71 years (range, 50-83 years), and average follow-up was 4.3 months (range, 1-7 months). Mean prostate volume was 32 mL (range, 16-38 mL). Five patients developed PSF after PVP and 3 patients after TURP. The most common postoperative symptoms included difficulty ambulating (100%) and pelvic, groin, and/or lower abdominal pain (85%). Associated diagnoses included osteitis pubis (38%) and urinoma (50%). Infectious complications were urinary tract infection (25%), osteomyelitis (38%), and infected urinoma (38%). Average time to diagnosis of PSF was 3.5 months (range, 0.5-11 months). Operative intervention was necessary in 75% of patients. CONCLUSION This is the first reported case series on the management of PSF after PVP or TURP. This complication can be difficult to diagnose, manage, and may cause significant patient morbidity. Management requires a multidisciplinary approach. Patients commonly present with non-urologic symptoms leading to a delay in diagnosis. Further studies are needed to assess the incidence and optimal management of this complication. (C) 2015 Elsevier Inc. C1 [Sanchez, Alejandro; Rodriguez, Dayron; Cheng, Jed-Sian; McGovern, Francis J.; Tabatabaei, Shahin] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Sanchez, A (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St,GRB 1102, Boston, MA 02114 USA. EM asanchez6@partners.org NR 16 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD JAN PY 2015 VL 85 IS 1 BP 172 EP 177 DI 10.1016/j.urology.2014.09.028 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA AX0NI UT WOS:000346648500042 PM 25444634 ER PT J AU Shrime, MG Sleemi, A Ravilla, TD AF Shrime, Mark G. Sleemi, Ambereen Ravilla, Thulasiraj D. TI Charitable Platforms in Global Surgery: A Systematic Review of their Effectiveness, Cost-Effectiveness, Sustainability, and Role Training SO WORLD JOURNAL OF SURGERY LA English DT Article ID MOBILE EAR SURGERY; INTRAMEDULLARY NAIL OPERATIONS; RESOURCE-LIMITED SETTINGS; INTRAOCULAR-LENS SURGERY; MIDDLE-INCOME COUNTRIES; CHRONIC OTITIS-MEDIA; RURAL EYE CAMP; UNITED-STATES; DEVELOPING-WORLD; CLEFT-LIP AB This study was designed to propose a classification scheme for platforms of surgical delivery in low- and middle-income countries (LMICs) and to review the literature documenting their effectiveness, cost-effectiveness, sustainability, and role in training. Approximately 28 % of the global burden of disease is surgical. In LMICs, much of this burden is borne by a rapidly growing international charitable sector, in fragmented platforms ranging from short-term trips to specialized hospitals. Systematic reviews of these platforms, across regions and across disease conditions, have not been performed. A systematic review of MEDLINE and EMBASE databases was performed from 1960 to 2013. Inclusion and exclusion criteria were defined a priori. Bibliographies of retrieved studies were searched by hand. Of the 8,854 publications retrieved, 104 were included. Surgery by international charitable organizations is delivered under two, specialized hospitals and temporary platforms. Among the latter, short-term surgical missions were the most common and appeared beneficial when no other option was available. Compared to other platforms, however, worse results and a lack of cost-effectiveness curtailed their role. Self-contained temporary platforms that did not rely on local infrastructure showed promise, based on very few studies. Specialized hospitals provided effective treatment and appeared sustainable; cost-effectiveness evidence was limited. Because the charitable sector delivers surgery in vastly divergent ways, systematic review of these platforms has been difficult. This paper provides a framework from which to study these platforms for surgery in LMICs. Given the available evidence, self-contained temporary platforms and specialized surgical centers appear to provide more effective and cost-effective care than short-term surgical mission trips, except when no other delivery platform exists. C1 [Shrime, Mark G.] Harvard Interfac Initiat Hlth Policy, Cambridge, MA 02138 USA. [Shrime, Mark G.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Shrime, Mark G.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. [Shrime, Mark G.] Childrens Hosp, Program Global Surg & Social Change, Boston, MA 02115 USA. [Sleemi, Ambereen] Maimonides Hosp, New York, NY USA. [Sleemi, Ambereen] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Ravilla, Thulasiraj D.] Lions Aravind Inst Community Ophthalmol, Madurai, Tamil Nadu, India. RP Shrime, MG (reprint author), Harvard Interfac Initiat Hlth Policy, 14 Story St,4th Floor, Cambridge, MA 02138 USA. EM shrime@gmail.com FU NCI NIH HHS [R25 CA092203] NR 123 TC 34 Z9 34 U1 3 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 EI 1432-2323 J9 WORLD J SURG JI World J.Surg. PD JAN PY 2015 VL 39 IS 1 BP 10 EP 20 DI 10.1007/s00268-014-2516-0 PG 11 WC Surgery SC Surgery GA AX2QQ UT WOS:000346789500002 PM 24682278 ER PT J AU Koo, CY Hyder, JA Wanderer, JP Eikermann, M Ramachandran, SK AF Koo, Chieh Yang Hyder, Joseph A. Wanderer, Jonathan P. Eikermann, Matthias Ramachandran, Satya Krishna TI A Meta-analysis of the Predictive Accuracy of Postoperative Mortality Using the American Society of Anesthesiologists' Physical Status Classification System SO WORLD JOURNAL OF SURGERY LA English DT Article ID DISEASE MELD SCORE; CARDIAC RISK INDEX; HIP FRACTURE; COLORECTAL-CANCER; HOSPITAL MORTALITY; HEPATOCELLULAR-CARCINOMA; PERIOPERATIVE MORTALITY; MULTIVARIATE-ANALYSIS; UROTHELIAL CARCINOMA; EMERGENCY LAPAROTOMY AB The American Society of Anesthesiologists' physical status (ASA) tool has been applied to determine compensation, risk adjustment and risk prediction, but little is known about the accuracy and generalizability of this tool for prediction of postoperative mortality. We systematically investigated prior published reports of associations between ASA physical status and mortality to test the hypothesis that ASA physical status will have varying accuracy in prediction of postoperative mortality across surgical populations with varying surgical risk of mortality. We used random effects models and metaregression to account for heterogeneity. Combining 77 studies with 165,705 patients, the ASA physical status tool demonstrated the following pooled performance (95 % confidence intervals)-sensitivity 0.74 (0.73, 0.74), specificity 0.67 (0.67, 0.67), and area under summary receiver operating curve 0.736 (0.725, 0.747). Metaregression revealed that study death rates and surgical specialty were significant factors. ASA physical status is a better predictor of postoperative mortality in settings with lower rather than higher death rates. C1 [Koo, Chieh Yang] Natl Univ Hlth Syst, Univ Med Cluster, Singapore 119074, Singapore. [Hyder, Joseph A.] Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. [Wanderer, Jonathan P.] Vanderbilt Univ, Dept Anesthesiol, Nashville, TN 37232 USA. [Eikermann, Matthias] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. [Eikermann, Matthias] Univ Klinikum Essen, Essen, Germany. [Ramachandran, Satya Krishna] Univ Michigan, Med Ctr Dr, Ann Arbor, MI 48109 USA. RP Eikermann, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesiol, Gray Bigelow 444,55 Fruit St, Boston, MA 02114 USA. EM meikermann@partners.org RI Ramachandran, Satya Krishna/P-6636-2016 OI Ramachandran, Satya Krishna/0000-0002-7176-6375 FU Merck; Sharpe and Dohme; Foundation for Anesthesia Education and Research (FAER) FX C.Y.K., J.A.H, J.P.W., and M.E. do not report any conflicts of interest. S.K.R. has worked as an ad-hoc paid consultant on the scientific advisory board of Galleon Pharmaceuticals, Horsham, PA, USA and Merck, Sharpe and Dohme in 2013. SKR has active research funding from Merck, Sharpe and Dohme in 2014. This funding is unrelated to this study. J.P.W. is funded, in part, by the Foundation for Anesthesia Education and Research (FAER) through a Health Services Research Mentored Research Training Grant. NR 103 TC 8 Z9 8 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 EI 1432-2323 J9 WORLD J SURG JI World J.Surg. PD JAN PY 2015 VL 39 IS 1 BP 88 EP 103 DI 10.1007/s00268-014-2783-9 PG 16 WC Surgery SC Surgery GA AX2QQ UT WOS:000346789500013 PM 25234196 ER PT J AU Auffermann, WF Chetlen, AL Colucci, AT DeQuesada, IM Grajo, JR Heller, MT Nowitzki, KM Sherry, SJ Tillack, AA AF Auffermann, William F. Chetlen, Alison L. Colucci, Andrew T. DeQuesada, Ivan M., II Grajo, Joseph R. Heller, Matthew T. Nowitzki, Kristina M. Sherry, Steven J. Tillack, Allison A. TI Online Social Networking for Radiology SO ACADEMIC RADIOLOGY LA English DT Article DE Social networking; radiology ID MEDIA; WEB AB Online social networking services have changed the way we interact as a society and offer many opportunities to improve the way we practice radiology and medicine in general. This article begins with an introduction to social networking. Next, the latest advances in online social networking are reviewed, and areas where radiologists and clinicians may benefit from these new tools are discussed. This article concludes with several steps that the interested reader can take to become more involved in online social networking. C1 [Auffermann, William F.; DeQuesada, Ivan M., II] Emory Univ, Sch Med, Dept Radiol & Imaging Sci, Atlanta, GA 30322 USA. [Chetlen, Alison L.] Penn State Milton S Hershey Med Ctr, Dept Radiol, Hershey, PA USA. [Colucci, Andrew T.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Grajo, Joseph R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Heller, Matthew T.] Univ Pittsburgh, Dept Radiol, Sch Med & Med Ctr, Pittsburgh, PA 15260 USA. [Nowitzki, Kristina M.] Univ Massachusetts, Dept Radiol, Worcester, MA USA. [Sherry, Steven J.] Univ Pittsburgh, Dept Radiol, Med Ctr, Pittsburgh, PA 15260 USA. [Tillack, Allison A.] Univ Washington, Med Ctr, Dept Radiol, Seattle, WA 98195 USA. RP Auffermann, WF (reprint author), Emory Univ, Sch Med, Dept Radiol & Imaging Sci, 1364 Clifton Rd NE, Atlanta, GA 30322 USA. EM wauffer@emory.edu OI Chetlen, Alison/0000-0001-5304-2392 NR 23 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 EI 1878-4046 J9 ACAD RADIOL JI Acad. Radiol. PD JAN PY 2015 VL 22 IS 1 BP 3 EP 13 DI 10.1016/j.acra.2014.07.021 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AX1FF UT WOS:000346692700002 PM 25262953 ER PT J AU Nishi, A Kawachi, I Koenen, KC Wu, K Nishihara, R Ogino, S AF Nishi, Akihiro Kawachi, Ichiro Koenen, Karestan C. Wu, Kana Nishihara, Reiko Ogino, Shuji TI Lifecourse Epidemiology and Molecular Pathological Epidemiology SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID LIFE-COURSE EPIDEMIOLOGY; COLORECTAL-CANCER; HEALTH; PREVENTION; PATHWAYS; SCIENCE; DISEASE C1 [Nishi, Akihiro] Yale Univ, Dept Sociol, New Haven, CT 06520 USA. [Nishi, Akihiro] Yale Univ, Yale Inst Network Sci, New Haven, CT 06520 USA. [Kawachi, Ichiro; Koenen, Karestan C.] Harvard Univ, Sch Med, Dept Social & Behav Sci, Cambridge, MA 02138 USA. [Wu, Kana; Nishihara, Reiko] Harvard Univ, Sch Med, Dept Nutr, Cambridge, MA 02138 USA. [Ogino, Shuji] Harvard Univ, Sch Med, Dept Epidemiol, Cambridge, MA 02138 USA. [Nishihara, Reiko; Ogino, Shuji] Harvard Univ, Sch Med, Sch Publ Hlth, Dept Med Oncol, Cambridge, MA 02138 USA. [Nishihara, Reiko; Ogino, Shuji] Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. [Ogino, Shuji] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Koenen, Karestan C.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. RP Nishi, A (reprint author), Yale Univ, Dept Sociol, 17 Hillhouse Ave, New Haven, CT 06520 USA. EM akihiro.nishi@yale.edu OI Nishi, Akihiro/0000-0003-1629-5985 FU Konosuke Matsushita Memorial Foundation; Japan Society for the Promotion of Science; NIH [R01 CA151993] FX This research was supported by a grant from The Konosuke Matsushita Memorial Foundation. AN was awarded by the Japan Society for the Promotion of Science for his research at Yale University. RN and SO were supported in part by NIH grant no. R01 CA151993 (to SO). NR 13 TC 7 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD JAN PY 2015 VL 48 IS 1 BP 116 EP 119 DI 10.1016/j.amepre.2014.09.031 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA AW7CQ UT WOS:000346422600015 PM 25528613 ER PT J AU Lillemoe, KD AF Lillemoe, Keith D. TI Changes at Annals of Surgery SO ANNALS OF SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Lillemoe, KD (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD JAN PY 2015 VL 261 IS 1 BP 1 EP 1 DI 10.1097/SLA.0000000000001028 PG 1 WC Surgery SC Surgery GA AW6XS UT WOS:000346409600032 PM 25599321 ER PT J AU Tsai, TC Orav, EJ Jha, AK AF Tsai, Thomas C. Orav, E. John Jha, Ashish K. TI Patient Satisfaction and Quality of Surgical Care in US Hospitals SO ANNALS OF SURGERY LA English DT Article DE efficiency; length of stay; Medicare; patient satisfaction; surgical quality ID UNITED-STATES; INPATIENT CARE; HCAHPS SURVEY; READMISSION; MORTALITY; OUTCOMES; SURGERY; RISK; EXPERIENCE; RATES AB Objective: The relationship between patient satisfaction and surgical quality is unclear for US hospitals. Using national data, we examined if hospitals with high patient satisfaction have lower levels of performance on accepted measures of the quality and efficiency of surgical care. Background: Federal policymakers have made patient satisfaction a core measure for the way hospitals are evaluated and paid through the value-based purchasing program. There is broad concern that performance on patient satisfaction may have little or even a negative correlation with the quality of surgical care, leading to potential trade-offs in efforts to improve patient experience with other surgical quality measures. Methods: We used the Hospital Consumer Assessment of Healthcare Providers and Systems survey data from 2010 and 2011 to assess performance on patient experience. We used national Medicare data on 6 common surgical procedures to calculate measures of surgical efficiency and quality: risk-adjusted length of stay, process score, risk-adjusted mortality rate, risk-adjusted readmission rate, and a composite z score across all 4 metrics. Multivariate models adjusting for hospital characteristics were used to assess the independent relationships between patient satisfaction and measures of surgical efficiency and quality. Results: Of the 2953 US hospitals that perform one of these 6 procedures, the median patient satisfaction score was 69.5% (interquartile range, 63% 75.5%). Length of stay was shorter in hospitals with the highest levels of patient satisfaction (7.1 days vs 7.7 days, P < 0.001). Adjusting for procedural volume and structural characteristics, institutions in the highest quartile of patient satisfaction had the higher process of care performance (96.5 vs 95.5, P < 0.001), lower readmission rates (12.3% vs 13.6%, P < 0.001), and lower mortality (3.1% vs 3.6%) than those in the lowest quartile. Hospitals with high patient satisfaction also had a higher composite score for quality across all measures (P < 0.001). Conclusions: Among US hospitals that perform major surgical procedures, hospitals with high patient satisfaction provided more efficient care and were associated with higher surgical quality. Our findings suggest there need not be a trade-off between good quality of care for surgical patients and ensuring a positive patient experience. C1 [Tsai, Thomas C.; Jha, Ashish K.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Tsai, Thomas C.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Orav, E. John] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Orav, E. John; Jha, Ashish K.] Brigham & Womens Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02115 USA. [Jha, Ashish K.] VA Boston Healthcare Syst, Boston, MA USA. RP Tsai, TC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA. EM ttsai@hsph.harvard.edu FU National Cancer Institute [R25CA92203] FX Supported by grant R25CA92203 (for Dr Tsai) from the National Cancer Institute. The authors declare no conflicts of interest. NR 28 TC 35 Z9 35 U1 3 U2 32 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD JAN PY 2015 VL 261 IS 1 BP 2 EP 8 DI 10.1097/SLA.0000000000000765 PG 7 WC Surgery SC Surgery GA AW6XS UT WOS:000346409600033 PM 24887985 ER PT J AU Ferrone, CR Marchegiani, G Hong, TS Ryan, DP Deshpande, V McDonnell, EI Sabbatino, F Santos, DD Allen, JN Blaszkowsky, LS Clark, JW Faris, JE Goyal, L Kwak, EL Murphy, JE Ting, DT Wo, JY Zhu, AX Warshaw, AL Lillemoe, KD Fernandez-del Castillo, C AF Ferrone, Cristina R. Marchegiani, Giovanni Hong, Theodore S. Ryan, David P. Deshpande, Vikram McDonnell, Erin I. Sabbatino, Francesco Santos, Daniela Dias Allen, Jill N. Blaszkowsky, Lawrence S. Clark, Jeffrey W. Faris, Jason E. Goyal, Lipika Kwak, Eunice L. Murphy, Janet E. Ting, David T. Wo, Jennifer Y. Zhu, Andrew X. Warshaw, Andrew L. Lillemoe, Keith D. Fernandez-del Castillo, Carlos TI Radiological and Surgical Implications of Neoadjuvant Treatment With FOLFIRINOX for Locally Advanced and Borderline Resectable Pancreatic Cancer SO ANNALS OF SURGERY LA English DT Article DE chemotherapy; downstaging; FOLFIRINOX; neoadjuvant therapy; pancreas cancer; pancreatic adenocarcinoma; PDAC; surgery ID LONG-TERM SURVIVAL; MINIMAL POSTOPERATIVE COMPLICATIONS; SINGLE-INSTITUTION EXPERIENCE; 1423 PANCREATICODUODENECTOMIES; SURGEONS CONTRIBUTION; PHASE-II; ADENOCARCINOMA; GEMCITABINE; RADIOTHERAPY; CHEMORADIATION AB Purpose: On the basis of the ACCORD trial, FOLFIRINOX is effective in metastatic pancreatic adenocarcinoma (PDAC), making it a rational choice for locally advanced PDAC (LA). Aims of this study are to evaluate the accuracy of imaging in determining the resectability of PDAC and to determine the surgical and clinicopathologic outcomes of pancreatic resections after neoadjuvant FOLFIRINOX therapy. Patients and Methods: Clinicopathologic data were retrospectively collected for surgical PDAC patients receiving neoadjuvant FOLFIRINOX or no neoadjuvant therapy between April 2011 and February 2014. Americas Hepato-Pancreato-Biliary Association/Society of Surgical Oncology/Society for Surgery of the Alimentary Tract consensus guidelines defined LA and borderline. Imaging was reviewed by a blinded senior pancreatic surgeon. Results: Of 188 patients undergoing resection for PDAC, 40 LA/borderline received FOLFIRINOX and 87 received no neoadjuvant therapy. FOLFIRINOX resulted in a significant decrease in tumor size, yet 19 patients were still classified as LA and 9 as borderline. Despite post-FOLFIRINOX imaging suggesting continued unresectability, 92% had an R0 resection. When compared with no neoadjuvant therapy, FOLFIRINOX resulted in significantly longer operative times (393 vs 300 minutes) and blood loss (600 vs 400 mL), but significantly lower operative morbidity (36% vs 63%) and no postoperative pancreatic fistulas. Length of stay (6 vs 7 days), readmissions (20% vs 30%), and mortality were equivalent (1% vs 0%). On final pathology, the FOLFIRINOX group had a significant decrease in lymph node positivity (35% vs 79%) and perineural invasion (72% vs 95%). Median follow-up was 11 months with a significant increase in overall survival with FOLFIRINOX. Conclusions: After neoadjuvant FOLFIRINOX imaging no longer predicts unresectability. Traditional pathologic predictors of survival are improved, and morbidity is decreased in comparison to patients with clearly resectable cancers at the time of presentation. C1 [Ferrone, Cristina R.; Marchegiani, Giovanni; Sabbatino, Francesco; Santos, Daniela Dias; Warshaw, Andrew L.; Lillemoe, Keith D.; Fernandez-del Castillo, Carlos] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02108 USA. [Hong, Theodore S.; Wo, Jennifer Y.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02108 USA. [Ryan, David P.; Deshpande, Vikram; McDonnell, Erin I.; Allen, Jill N.; Blaszkowsky, Lawrence S.; Clark, Jeffrey W.; Faris, Jason E.; Goyal, Lipika; Kwak, Eunice L.; Murphy, Janet E.; Ting, David T.; Zhu, Andrew X.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02108 USA. RP Ferrone, CR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, WANG 460,15 Parkman St, Boston, MA 02108 USA. EM cferrone@partners.org RI Sabbatino, Francesco/F-4992-2014; OI Sabbatino, Francesco/0000-0001-6431-8278; Ting, David/0000-0002-3261-2322 FU NCI NIH HHS [K12 CA087723, P50 CA127003] NR 24 TC 86 Z9 92 U1 3 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD JAN PY 2015 VL 261 IS 1 BP 12 EP 17 DI 10.1097/SLA.0000000000000867 PG 6 WC Surgery SC Surgery GA AW6XS UT WOS:000346409600035 PM 25599322 ER PT J AU Deng, L Huang, L Sun, Y Heath, JM Wu, H Chen, YB AF Deng, Liang Huang, Lu Sun, Yong Heath, Jack M. Wu, Hui Chen, Yabing TI Inhibition of FOXO1/3 Promotes Vascular Calcification SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE AKT; FOXO1/3; PTEN; Runx2; ubiquitination; vascular calcification ID SMOOTH-MUSCLE-CELLS; TUMOR-SUPPRESSOR GENE; OSTEOBLAST DIFFERENTIATION; TRANSCRIPTION FACTORS; NEOINTIMA FORMATION; PROSTATE-CANCER; PTEN; RUNX2; INACTIVATION; AKT AB Objective-Vascular calcification is a characteristic feature of atherosclerosis, diabetes mellitus, and end-stage renal disease. We have demonstrated that activation of protein kinase B (AKT) upregulates runt-related transcription factor 2 (Runx2), a key osteogenic transcription factor that is crucial for calcification of vascular smooth muscle cells (VSMC). Using mice with SMC-specific deletion of phosphatase and tensin homolog (PTEN), a major negative regulator of AKT, the present studies uncovered a novel molecular mechanism underlying PTEN/AKT/FOXO (forkhead box O)-mediated Runx2 upregulation and VSMC calcification. Approach and Results-SMC-specific PTEN deletion mice were generated by crossing PTEN floxed mice with SM22 alpha-Cre transgenic mice. The PTEN deletion resulted in sustained activation of AKT that upregulated Runx2 and promoted VSMC calcification in vitro and arterial calcification ex vivo. Runx2 knockdown did not affect proliferation but blocked calcification of the PTEN-deficient VSMC, suggesting that PTEN deletion promotes Runx2-depedent VSMC calcification that is independent of proliferation. At the molecular level, PTEN deficiency increased the amount of Runx2 post-transcriptionally by inhibiting Runx2 ubiquitination. AKT activation increased phosphorylation of FOXO1/3 that led to nuclear exclusion of FOXO1/3. FOXO1/3 knockdown in VSMC phenocopied the PTEN deficiency, demonstrating a novel function of FOXO1/3, as a downstream signaling of PTEN/AKT, in regulating Runx2 ubiquitination and VSMC calcification. Using heterozygous SMC-specific PTEN-deficient mice and atherogenic ApoE(-/-) mice, we further demonstrated AKT activation, FOXO phosphorylation, and Runx2 ubiquitination in vascular calcification in vivo. Conclusions-Our studies have determined a new causative effect of SMC-specific PTEN deficiency on vascular calcification and demonstrated that FOXO1/3 plays a crucial role in PTEN/AKT-modulated Runx2 ubiquitination and VSMC calcification. C1 [Deng, Liang; Huang, Lu; Sun, Yong; Heath, Jack M.; Chen, Yabing] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL USA. [Wu, Hui] Univ Alabama Birmingham, Dept Pediat Dent, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Chen, Yabing] Univ Alabama Birmingham, Dept Res Serv, Birmingham, AL USA. RP Chen, YB (reprint author), 1825 Univ Blvd,630 Shelby Biomed Res Bldg, Birmingham, AL 35294 USA. EM ybchen@uab.edu FU National Institutes of Health [HL092215, DK100847]; Veterans Administration [BX000369, BX001591]; American Heart Association [12PRE11840009] FX This work was supported in part by grants from the National Institutes of Health HL092215 and DK100847 and Veterans Administration BX000369 and BX001591 (project 2) to Y. Chen. J.M. Heath was supported by American Heart Association Grant 12PRE11840009. NR 49 TC 12 Z9 12 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JAN PY 2015 VL 35 IS 1 BP 175 EP 183 DI 10.1161/ATVBAHA.114.304786 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AW9EU UT WOS:000346561100025 PM 25378413 ER PT J AU Cui, J Kessinger, CW McCarthy, JR Sosnovik, DE Libby, P Thadhani, RI Jaffer, FA AF Cui, Jie Kessinger, Chase W. McCarthy, Jason R. Sosnovik, David E. Libby, Peter Thadhani, Ravi I. Jaffer, Farouc A. TI In Vivo Nanoparticle Assessment of Pathological Endothelium Predicts the Development of Inflow Stenosis in Murine Arteriovenous Fistula SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE arteriovenous fistula; endothelium; imaging; stenosis ID VASCULAR ACCESS MORBIDITY; HEMODIALYSIS-PATIENTS; MOUSE MODEL; ADHESION; GRAFTS; ATHEROSCLEROSIS; INFLAMMATION; DYSFUNCTION; ULTRASOUND; EXPRESSION AB Objective-In vivo assessment of pathological endothelium within arteriovenous fistula (AVF) could provide new insights into inflow stenosis, a common cause of AVF primary failure in end-stage renal disease patients. Here we developed nanoparticle-based imaging strategies to assess pathological endothelium in vivo and elucidate its relationship to neointimal hyperplasia formation in AVF. Approach and Results-Jugular-carotid AVFs were created in C57BL/6 mice (n=38). Pathological endothelium in the AVF was visualized and quantified in vivo using dextranated magnetofluorescent nanoparticles (CLIO-VT680 [cross-linked iron oxide-VivoTag680]). At day 14, CLIO-VT680 was deposited in AVF, but only minimally in sham-operated arteries. Transmission electron microscopy revealed that CLIO-VT680 resided within endothelial cells and in the intimal extracellular space. Endothelial cells of AVF, but not control arteries, expressed vascular cell adhesion molecule-1 and showed augmented endothelial permeability near the anastomosis. Intravital microscopy demonstrated that CLIO-VT680 deposited most intensely near the AVF anastomosis (P<0.0001). The day 14 intravital microscopy CLIO-VT680 signal predicted the subsequent site and magnitude of AVF neointimal hyperplasia at day 42 (r=0.58, P<0.05). CLIO-VT680 deposition in AVF was further visualized by ex vivo MRI. Conclusions-AVF develop a pathological endothelial response that can be assessed in vivo via nanoparticle-enhanced imaging. AVF endothelium is activated and exhibits augmented permeability, offering a targeting mechanism for nanoparticle deposition and retention in pathological endothelium. The in vivo AVF nanoparticle signal identified and predicted subsequent inflow neointimal hyperplasia. This approach could be used to test therapeutic interventions aiming to restore endothelial health and to decrease early AVF failure caused by inflow stenosis. C1 [Cui, Jie; Kessinger, Chase W.; Sosnovik, David E.; Jaffer, Farouc A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Libby, Peter] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Cui, Jie; Thadhani, Ravi I.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [McCarthy, Jason R.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Sosnovik, David E.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Jaffer, Farouc A.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Jaffer, FA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Simches Res Bldg Room 3206, Boston, MA 02114 USA. EM fjaffer@mgh.harvard.edu FU American Society of Nephrology; National Institutes of Health (NIH) [R01 HL108229, R01 HL080472]; American Heart Association [13GRNT17060040]; NIH [T32 HL076136, P41 E8015903-02S1]; Nephrology Division at Massachusetts General Hospital FX This study was supported by grants from the American Society of Nephrology Ben J. Lipps Research Fellowship (to J. Cui), National Institutes of Health (NIH) R01 HL108229 (F.A. Jaffer), R01 HL080472 (P. Libby), American Heart Association Grant-in-Aid No. 13GRNT17060040 (F.A. Jaffer), NIH T32 HL076136 (C.W. Kessinger), NIH P41 E8015903-02S1 (C.P. Lin) and the Nephrology Division at Massachusetts General Hospital. NR 37 TC 2 Z9 2 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JAN PY 2015 VL 35 IS 1 BP 189 EP 196 DI 10.1161/ATVBAHA.114.304483 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AW9EU UT WOS:000346561100027 PM 25395614 ER PT J AU Tung, N Battelli, C Allen, B Kaldate, R Bhatnagar, S Bowles, K Timms, K Garber, JE Herold, C Ellisen, L Krejdovsky, J DeLeonardis, K Sedgwick, K Soltis, K Roa, B Wenstrup, RJ Hartman, AR AF Tung, Nadine Battelli, Chiara Allen, Brian Kaldate, Rajesh Bhatnagar, Satish Bowles, Karla Timms, Kirsten Garber, Judy E. Herold, Christina Ellisen, Leif Krejdovsky, Jill DeLeonardis, Kim Sedgwick, Kristin Soltis, Kathleen Roa, Benjamin Wenstrup, Richard J. Hartman, Anne-Renee TI Frequency of Mutations in Individuals With Breast Cancer Referred for BRCA1 and BRCA2 Testing Using Next-Generation Sequencing With a 25-Gene Panel SO CANCER LA English DT Article DE high-throughput nucleotide sequencing; breast neoplasms; genetic testing; BRCA1; BRCA2 ID LI-FRAUMENI-SYNDROME; DIFFUSE GASTRIC-CANCER; OVARIAN-CANCER; GERMLINE MUTATIONS; SUSCEPTIBILITY GENE; CLINICAL CHARACTERISTICS; CONFER SUSCEPTIBILITY; COLORECTAL-CANCER; PANCREATIC-CANCER; BARD1 MUTATIONS AB BACKGROUNDNext-generation sequencing (NGS) allows for simultaneous sequencing of multiple cancer susceptibility genes and, for an individual, may be more efficient and less expensive than sequential testing. The authors assessed the frequency of deleterious germline mutations among individuals with breast cancer who were referred for BRCA1 and BRCA2 (BRCA1/2) gene testing using a panel of 25 genes associated with inherited cancer predisposition. METHODSThis was a cross-sectional study using NGS in 2158 individuals, including 1781 who were referred for commercial BRCA1/2 gene testing (cohort 1) and 377 who had detailed personal and family history and had previously tested negative for BRCA1/2 mutations (cohort 2). RESULTSMutations were identified in 16 genes, most frequently in BRCA1, BRCA2, CHEK2, ATM, and PALB2. Among the participants in cohort 1, 9.3% carried a BRCA1/2 mutation, 3.9% carried a mutation in another breast/ovarian cancer susceptibility gene, and 0.3% carried an incidental mutation in another cancer susceptibility gene unrelated to breast or ovarian cancer. In cohort 2, the frequency of mutations in breast/ovarian-associated genes other than BRCA1/2 was 2.9%, and an additional 0.8% had an incidental mutation. In cohort 1, Lynch syndrome-related mutations were identified in 7 individuals. In contrast to BRCA1/2 mutations, neither age at breast cancer diagnosis nor family history of ovarian or young breast cancer predicted for other mutations. The frequency of mutations in genes other than BRCA1/2 was lower in Ashkenazi Jews compared with non-Ashkenazi individuals (P=.026). CONCLUSIONSUsing an NGS 25-gene panel, the frequency of mutations in genes other than BRCA1/2 was 4.3%, and most mutations (3.9%) were identified in genes associated with breast/ovarian cancer. Cancer 2015;121:25-33. (c) 2014 American Cancer Society. Using a next-generation sequencing 25-gene panel, the frequency of mutations for patients with breast cancer in genes other than BRCA1/2 is 4.3%, and most of the mutations (3.9%) are in genes associated with breast/ovarian cancer. Approximately half of patients with mutations in genes other than BRCA1/2 are identified in moderate-penetrance genes for which the efficacy of medical management is less well defined. C1 [Tung, Nadine; Battelli, Chiara; Herold, Christina] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Tung, Nadine; Garber, Judy E.; Herold, Christina; Ellisen, Leif] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Allen, Brian; Kaldate, Rajesh; Hartman, Anne-Renee] Myriad Genet Labs Inc, Clin Affairs, Salt Lake City, UT USA. [Bhatnagar, Satish] Myriad Genet Inc, Tech & Prod Dev, Salt Lake City, UT USA. [Bowles, Karla; Roa, Benjamin] Myriad Genet Labs Inc, Diagnost Dev, Salt Lake City, UT USA. [Timms, Kirsten] Myriad Genet Inc, Res, Salt Lake City, UT USA. [Garber, Judy E.] Dana Farber Canc Inst, Div Populat Sci & Adult Oncol, Boston, MA 02115 USA. [Ellisen, Leif] Massachusetts Gen Hosp, Dept Hematol Oncol & Med, Boston, MA 02114 USA. [Krejdovsky, Jill; DeLeonardis, Kim; Sedgwick, Kristin; Soltis, Kathleen] Beth Israel Deaconess Med Ctr, Canc Genet & Prevent Program, Boston, MA 02215 USA. [Wenstrup, Richard J.] Myriad Genet Labs Inc, Med Serv, Salt Lake City, UT USA. RP Tung, N (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215 USA. EM ntung@bidmc.harvard.edu FU Breast Cancer Research Foundation FX This research was supported by grants from the Breast Cancer Research Foundation. NR 53 TC 80 Z9 83 U1 4 U2 40 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 JAN 1 PY 2015 VL 121 IS 1 BP 25 EP 33 DI 10.1002/cncr.29010 PG 9 WC Oncology SC Oncology GA AW8CF UT WOS:000346487500008 PM 25186627 ER PT J AU Braun, IM Rao, SR Meyer, FL Fedele, G AF Braun, Ilana M. Rao, Sowmya R. Meyer, Fremonta L. Fedele, Giuseppe TI Patterns of Psychiatric Medication Use Among Nationally Representative Long-Term Cancer Survivors and Controls SO CANCER LA English DT Article DE psychosocial oncology; epidemiology; cancer survivors; psychopharmacology; psychiatric diagnosis ID COMORBIDITY SURVEY REPLICATION; BREAST-CANCER; HEALTH; SYMPTOMS; DISTRESS; SAMPLE; CARE AB BACKGROUNDInvestigations of long-term cancer survivors (LTCS) indicate that this population is not appreciably different from cancer-naive peers with respect to several neuropsychiatric domains. The current study sought to determine whether differences in psychiatric medication use might help to explain the negative findings. METHODSIn a nationally representative sample, 5692 subjects were queried for cancer history, psychiatric diagnoses, and psychotropic medication use. The LTCS were defined as those individuals who were 5 years from diagnosis and whose cancer was in remission or cured. Odds ratios and 95% confidence intervals were obtained from multivariable logistic regression models evaluating the relationship between cancer status and use of psychiatric medications. The interaction between case/control status and psychiatric diagnoses was also tested in a logistic regression model to predict psychotropic medication use. RESULTSA total of 225 participants met the criteria for LTCS and 3953 met the criteria for cancer-naive controls (CNC). The LTCS were no more likely than CNC to carry a psychiatric diagnosis. Despite the LTCS reporting somewhat greater psychotropic medication use compared with the CNC (28.8% vs 22.3%), unadjusted and adjusted differences did not reach statistical significance, possibly due to sample size. The interaction between case/control status and carrying a psychiatric diagnosis was not found to be significantly associated with receiving a psychiatric medication. CONCLUSIONSLTCS and CNC demonstrated comparable rates of psychiatric prescription medication use. The relationship between taking a psychiatric medication and carrying a psychiatric diagnosis was not found to be significantly different between the case and control groups. These findings contribute to an emerging hypothesis that in general LTCS are not a particularly psychiatrically vulnerable group. Cancer 2015;121:132-138. (c) 2014 American Cancer Society. Long-term cancer survivors and cancer-naive controls demonstrate comparable rates of psychiatric prescription medication use. These findings contribute to an emerging hypothesis that, in general, long-term cancer survivors are not a particularly psychiatrically vulnerable group. C1 [Braun, Ilana M.; Meyer, Fremonta L.; Fedele, Giuseppe] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Adult Psychosocial Oncol, Boston, MA 02115 USA. [Rao, Sowmya R.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Rao, Sowmya R.] Vet Adm Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Fedele, Giuseppe] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. RP Braun, IM (reprint author), Dana Farber Canc Inst, Div Adult Psychosocial Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM ibraun@partners.org FU Harvard Medical School Shore Award FX This research was generously supported by a Harvard Medical School Shore Award. NR 19 TC 2 Z9 2 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 JAN 1 PY 2015 VL 121 IS 1 BP 132 EP 138 DI 10.1002/cncr.29014 PG 7 WC Oncology SC Oncology GA AW8CF UT WOS:000346487500020 PM 25208515 ER PT J AU Badr, H Smith, CB Goldstein, NE Gomez, JE Redd, WH AF Badr, Hoda Smith, Cardinale B. Goldstein, Nathan E. Gomez, Jorge E. Redd, William H. TI Dyadic Psychosocial Intervention for Advanced Lung Cancer Patients and Their Family Caregivers: Results of a Randomized Pilot Trial SO CANCER LA English DT Article DE caregivers; couples; lung cancer; palliative care; psychological distress; psychosocial intervention; supportive care ID OF-LIFE CARE; PALLIATIVE CARE; INFORMAL CAREGIVERS; DISTRESS; END; METAANALYSIS; BEREAVEMENT; GUIDELINES; MANAGEMENT; SYSTEM AB BACKGROUNDAdvanced lung cancer (LC) patients and their families have reported low self-efficacy for self-care/caregiving and high rates of distress, yet few programs exist to address their supportive care needs during treatment. This pilot study examined the feasibility, acceptability, and preliminary efficacy of a 6-session, telephone-based dyadic psychosocial intervention that was developed for advanced LC patients and their caregivers. The program was grounded in self-determination theory (SDT), which emphasizes the importance of competence (self-efficacy), autonomy (sense of choice/volition), and relatedness (sense of belonging/connection) for psychological functioning. The primary outcomes were patient and caregiver psychological functioning (depression/anxiety) and caregiver burden. The secondary outcomes were the SDT constructs of competence, autonomy, and relatedness. METHODSThirty-nine advanced LC patients who were within 1 month of treatment initiation (baseline) and their caregivers (51% spouses/partners) completed surveys and were randomized to the intervention or usual medical care. Eight weeks after baseline, they completed follow-up surveys. RESULTSSolid recruitment (60%) and low attrition rates demonstrated feasibility. Strong program evaluations (mean, 8.6/10) and homework completion rates (88%) supported acceptability. Participants receiving the intervention evidenced significant improvements (P<.0001) in depression, anxiety, and caregiver burden in comparison with usual medical care. Large effect sizes (d1.2) favoring the intervention were also found for patient and caregiver competence and relatedness and for caregiver autonomous motivation for providing care. CONCLUSIONThese findings support intervention feasibility, acceptability, and preliminary efficacy. By empowering families with the skills to coordinate care and meet the challenges of LC together, this intervention holds great promise for improving palliative/supportive care services in cancer. Cancer 2015;121:150-158. (c) 2014 American Cancer Society. Advanced lung cancer patients and their caregivers who receive an intervention show significant improvements in depression, anxiety, and caregiver burden in comparison with those receiving usual medical care. Large effect sizes (d>1.2) are also shown for patient and caregiver competence and relatedness and caregiver autonomous motivation for providing care. C1 [Badr, Hoda; Redd, William H.] Icahn Sch Med Mt Sinai, Dept Oncol Sci, New York, NY 10029 USA. [Smith, Cardinale B.] Icahn Sch Med Mt Sinai, Dept Med, Div Hematol & Med Oncol, New York, NY 10029 USA. [Smith, Cardinale B.; Goldstein, Nathan E.; Gomez, Jorge E.] Icahn Sch Med Mt Sinai, Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Goldstein, Nathan E.] James J Peters VA Med Ctr, Geriatr Res Educ & Clin Care Unit, Bronx, NY USA. RP Badr, H (reprint author), Icahn Sch Med Mt Sinai, Dept Oncol Sci, One Gustave L Levy Pl,Box 1130, New York, NY 10029 USA. EM hoda.badr@mssm.edu FU [P30 AG028741] FX This work was supported by a pilot grant awarded to Hoda Badr under P30 AG028741 (Albert Siu, MD, principal investigator). NR 34 TC 16 Z9 17 U1 6 U2 27 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 JAN 1 PY 2015 VL 121 IS 1 BP 150 EP 158 DI 10.1002/cncr.29009 PG 9 WC Oncology SC Oncology GA AW8CF UT WOS:000346487500022 PM 25209975 ER PT J AU Tremmel, JA Patel, RAG Bhatt, DL Cilingiroglu, M Pinto, DS Dean, LS Grines, CL AF Tremmel, Jennifer A. Patel, Rajan A. G. Bhatt, Deepak L. Cilingiroglu, Mehmet Pinto, Duane S. Dean, Larry S. Grines, Cindy L. TI Commentary on Highlighted Late Breaking Trials in Interventional Cardiology at ESC, VIVA, TCT, and AHA 2013 SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE stents; valvular heart disease; peripheral arterial disease; antithrombotics; myocardial infarction; review ID PERCUTANEOUS CORONARY INTERVENTION; FRACTIONAL FLOW RESERVE; ATHEROSCLEROTIC RENOVASCULAR DISEASE; NITINOL STENT IMPLANTATION; RANDOMIZED CLINICAL-TRIAL; MYOCARDIAL-INFARCTION; RESISTANT HYPERTENSION; BALLOON ANGIOPLASTY; RENAL DENERVATION; ARTERY STENOSIS AB With the plethora of clinical trials, it is difficult for busy interventional cardiologists to stay up to date. Therefore, the SCAI publications committee concisely summarizes and provides editorial commentary on the most important trials from recent, large international meetings. The intent is to provide this summary every six months to allow quick assimilation of trial results into interventional practice. (c) 2014 Wiley Periodicals, Inc. C1 [Tremmel, Jennifer A.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Patel, Rajan A. G.] Ochsner Med Ctr, John Ochsner Heart & Vasc Inst, New Orleans, LA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.; Pinto, Duane S.] Harvard Univ, Sch Med, Boston, MA USA. [Cilingiroglu, Mehmet] Univ Arkansas Med Sci, Arkansas Heart Hosp, Little Rock, AR 72205 USA. [Pinto, Duane S.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Dean, Larry S.] Univ Washington, Med Ctr, Seattle, WA 98195 USA. [Grines, Cindy L.] Detroit Med Ctr Cardiovasc Inst, Detroit, MI USA. RP Tremmel, JA (reprint author), 300 Pasteur Dr,Room H2103, Stanford, CA 94305 USA. EM jtremmel@stanford.edu NR 32 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 EI 1522-726X J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD JAN 1 PY 2015 VL 85 IS 1 BP 95 EP 103 DI 10.1002/ccd.25635 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AW7ZI UT WOS:000346479900025 PM 25115350 ER PT J AU Murphy, JM Blais, M Baer, L McCarthy, A Kamin, H Masek, B Jellinek, M AF Murphy, J. Michael Blais, Mark Baer, Lee McCarthy, Alyssa Kamin, Hayley Masek, Bruce Jellinek, Michael TI Measuring outcomes in outpatient child psychiatry: Reliable improvement, deterioration, and clinically significant improvement SO CLINICAL CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Child mental health; clinically significant improvement; outcomes measurement; reliable change; reliable deterioration ID PEDIATRIC SYMPTOM CHECKLIST; ASSESSMENT SCALE CGAS; MENTAL-HEALTH; PSYCHOSOCIAL PROBLEMS; PRIMARY-CARE; PSYCHOTHERAPY; SETTINGS; TREAT; METAANALYSIS; RELIABILITY AB Given the increasing interest in demonstrating effectiveness in psychiatric treatment, the current paper seeks to advance outcome measurement in child psychiatry by demonstrating how more informative analytic strategies can be used to evaluate treatment in a real world setting using a brief, standardized parent-report measure. Questionnaires were obtained at intake for 1294 patients. Of these, 695 patients entered treatment and 531 (74%) had complete forms at intake and follow-up. Using this sample, we analyzed the data to determine effect sizes, rates of reliable improvement and deterioration, and rates of clinically significant improvement. Findings highlighted the utility of these approaches for evaluating treatment outcomes. Further suggestions for improving outcome measurement and evaluation are provided. C1 [Murphy, J. Michael; Blais, Mark; Baer, Lee; McCarthy, Alyssa; Masek, Bruce] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Murphy, J. Michael; Blais, Mark; Baer, Lee; Masek, Bruce; Jellinek, Michael] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Kamin, Hayley] Univ Florida, Dept Psychol, Gainesville, FL 32611 USA. [Jellinek, Michael] Partners Healthcare, Boston, MA USA. RP Murphy, JM (reprint author), Massachusetts Gen Hosp, 55 Fruit St,YAW 6A, Boston, MA 02114 USA. EM mmurphy6@partners.org FU Fuss Family Fund FX This work was supported by the Fuss Family Fund (JMM; to Newton Wellesley Hospital). NR 49 TC 4 Z9 4 U1 3 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1359-1045 EI 1461-7021 J9 CLIN CHILD PSYCHOL P JI Clin. Child Psychol. Psychiatry PD JAN PY 2015 VL 20 IS 1 BP 39 EP 52 DI 10.1177/1359104513494872 PG 14 WC Psychology, Clinical; Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA AW8LM UT WOS:000346513500004 PM 23838693 ER PT J AU Mak, RH Hermann, G Lewis, JH Aerts, HJWL Baldini, EH Chen, AB Colson, YL Hacker, FH Kozono, D Wee, JO Chen, YH Catalano, PJ Wong, KK Sher, DJ AF Mak, Raymond H. Hermann, Gretchen Lewis, John H. Aerts, Hugo J. W. L. Baldini, Elizabeth H. Chen, Aileen B. Colson, Yolonda L. Hacker, Fred H. Kozono, David Wee, Jon O. Chen, Yu-Hui Catalano, Paul J. Wong, Kwok-Kin Sher, David J. TI Outcomes by Tumor Histology and KRAS Mutation Status After Lung Stereotactic Body Radiation Therapy for Early-Stage Non-Small-Cell Lung Cancer SO CLINICAL LUNG CANCER LA English DT Article DE Early stage; KRAS; Non-small-cell lung cancer; Stereotactic body radiotherapy ID GROWTH-FACTOR RECEPTOR; PROSPECTIVE PHASE-II; RAS MUTATIONS; CHEMOTHERAPY; ADENOCARCINOMA; TRIAL; EGFR; RADIOTHERAPY; GEFITINIB; CARCINOMA AB We analyzed outcomes after lung stereotactic body radiotherapy (SBRT) for early-stage non-small-cell lung carcinoma in patients by histology and KRAS mutation status. Histology was not associated with outcomes, but KRAS mutation was associated with lower freedom from recurrence on univariable analysis and decreased cancer-specific survival on multivariable analysis. Given the small sample sizes, these results are hypothesis generating, and further study of SBRT outcomes by tumor genotype in larger data sets is needed. Background: We analyzed outcomes after lung stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung-carcinoma (NSCLC) by histology and KRAS genotype. Patients and Methods: We included 75 patients with 79 peripheral tumors treated with SBRT (18 Gy x 3 or 10 to 12 Gy x 5) at our institution from 2009 to 2012. Genotyping for KRAS mutations was performed in 10 patients. Outcomes were analyzed by the Kaplan-Meier method/Cox regression, or cumulative incidence method/Fine-Gray analysis. Results: The median patient age was 74 (range, 46 to 93) years, and Eastern Cooperative Oncology Group performance status was 0 to 1 in 63%. Tumor histology included adenocarcinoma (44%), squamous cell carcinoma (25%), and NSCLC (18%). Most tumors were T1a (54%). Seven patients had KRAS-mutant tumors (9%). With a median follow-up of 18.8 months among survivors, the 1-year estimate of overall survival was 88%, cancer-specific survival (CSS) 92%, primary tumor control 94%, and freedom from recurrence (FFR) 67%. In patients with KRAS-mutant tumors, there was a significantly lower tumor control (67% vs. 96%; P = .04), FFR (48% vs. 69%; P = .03), and CSS (75% vs. 93%; P = .05). On multivariable analysis, histology was not associated with outcomes, but KRAS mutation (hazard ratio, 10.3; 95% confidence interval, 2.3-45.6; P = .0022) was associated with decreased CSS after adjusting for age. Conclusion: In this SBRT series, histology was not associated with outcomes, but KRAS mutation was associated with lower FFR on univariable analysis and decreased CSS on multivariable analysis. Because of the small sample size, these hypothesis-generating results need to be studied in larger data sets. C1 [Mak, Raymond H.; Hermann, Gretchen; Lewis, John H.; Aerts, Hugo J. W. L.; Baldini, Elizabeth H.; Chen, Aileen B.; Hacker, Fred H.; Kozono, David] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Mak, Raymond H.; Lewis, John H.; Aerts, Hugo J. W. L.; Baldini, Elizabeth H.; Chen, Aileen B.; Colson, Yolonda L.; Hacker, Fred H.; Kozono, David; Wee, Jon O.; Wong, Kwok-Kin] Harvard Univ, Sch Med, Boston, MA USA. [Aerts, Hugo J. W. L.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Colson, Yolonda L.; Wee, Jon O.] Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA. [Chen, Yu-Hui; Catalano, Paul J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Catalano, Paul J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Wong, Kwok-Kin] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Wong, Kwok-Kin] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA USA. [Sher, David J.] Rush Univ, Dept Radiat Oncol, Med Ctr, Chicago, IL 60612 USA. RP Mak, RH (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM rmak@lroc.harvard.edu RI Aerts, Hugo/P-6350-2015 OI Aerts, Hugo/0000-0002-2122-2003 FU American Cancer Society; American Society of Radiation Oncology; Varian Medical Systems; Boehringer-Ingelheim Inc; AstraZeneca; Takeda FX A.B.C. reports grant support from the American Cancer Society and American Society of Radiation Oncology, unrelated to the current study. J.H.L. reports grant support from Varian Medical Systems, unrelated to the current study. R.H.M. reports past consulting fees from Boehringer-Ingelheim Inc, unrelated to the current study. K.K.W. reports grant support from AstraZeneca and Takeda, unrelated to the current study. The other authors have no conflicts to report. NR 22 TC 13 Z9 13 U1 4 U2 15 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1525-7304 EI 1938-0690 J9 CLIN LUNG CANCER JI Clin. Lung Cancer PD JAN PY 2015 VL 16 IS 1 BP 24 EP 32 DI 10.1016/j.cllc.2014.09.005 PG 9 WC Oncology SC Oncology GA AW8CW UT WOS:000346489300004 PM 25450872 ER PT J AU Kuiper, JL Heideman, DAM Wurdinger, T Grunberg, K Groen, HJM Smit, EF AF Kuiper, Justine L. Heideman, Danielle A. M. Wurdinger, Tom Grunberg, Katrien Groen, Harry J. M. Smit, Egbert F. TI Rationale and Study Design of the IRENE-Trial (NVALT-16): A Phase II Trial to Evaluate Iressa Rechallenge in Advanced NSCLC Patients With an Activating EGFR Mutation Who Responded to an EGFR-TKI Used As First-Line or Previous Treatment SO CLINICAL LUNG CANCER LA English DT Editorial Material DE Drug holiday; EGFR; NSCLC; TKI; TKI-resistance ID CELL LUNG-CANCER; TYROSINE KINASE INHIBITORS; FACTOR RECEPTOR MUTATIONS; ACQUIRED-RESISTANCE; INITIAL GEFITINIB; OPEN-LABEL; RETROSPECTIVE ANALYSIS; RETREATMENT; CHEMOTHERAPY; ADENOCARCINOMA AB Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have shown improved progression-free survival (PFS) and overall survival (OS) over chemotherapy in a molecularly defined subgroup of advanced non-small-cell lung cancer (NSCLC) patients (ie, patients with an activating mutation in the EGFR gene). Nevertheless, all EGFR-mutated NSCLC patients develop TKI resistance eventually and there is no registered treatment or therapeutic strategy available for these patients. Several retrospective or small cohort studies have described patients who re-responded to EGFR-TKI treatment after a TKI-free interval ('drug holiday'). To date, no large prospective evaluation of the clinical effects of EGFR-TKI rechallenge in EGFR-mutated NSCLC patients has been performed. Patients and Methods: The IRENE (Iressa RE-challenge in advanced, EGFR-mutated NSCLC patients who responded to an EGFR-TKI used as first-line or previous treatment) (Dutch association for pulmonologists [NVALT]-16) trial is a multicenter, open-label, single-arm, single-stage, phase II study to evaluate gefitinib rechallenge in EGFR-mutated NSCLC patients who were previously treated with a TKI followed by a subsequent line of treatment (excluding EGFR-TKIs). The primary objective is disease control rate according to Response Evaluation Criteria in Solid Tumors criteria. Secondary objectives are objective response rate, PFS, OS, mutation characterization of sequential biopsies, VeriStrat correlation to PFS and OS, analysis of tumor-derived RNA in blood platelets and analysis of cell-free DNA in blood plasma. Results: The IRENE (NVALT-16) trial will evaluate the safety, efficacy, and feasibility of readministration of gefitinib after an EGFR-TKI-free interval in EGFR-mutated NSCLC patients. Conclusion: The study will evaluate gefitinib re-challenge in EGFR-mutated NSCLC patients. The study will also provide more insight into the dynamic development of molecular characteristics of EGFR-mutated NSCLC along the course of the disease. (C) 2015 Elsevier Inc. All rights reserved. C1 [Kuiper, Justine L.; Smit, Egbert F.] Vrije Univ Amsterdam, Med Ctr, Dept Pulm Dis, 4A48,POB 7057, NL-1007 MB Amsterdam, Netherlands. [Heideman, Danielle A. M.; Grunberg, Katrien] Vrije Univ Amsterdam, Med Ctr, Dept Pathol, NL-1007 MB Amsterdam, Netherlands. [Wurdinger, Tom] Vrije Univ Amsterdam, Med Ctr, Dept Neurosurg, NL-1007 MB Amsterdam, Netherlands. [Wurdinger, Tom] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Wurdinger, Tom] ThromboDX BV, Amsterdam, Netherlands. [Groen, Harry J. M.] Univ Groningen, Univ Med Ctr Groningen, Dept Pulm Dis, Groningen, Netherlands. RP Kuiper, JL (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Pulm Dis, 4A48,POB 7057, NL-1007 MB Amsterdam, Netherlands. EM jl.kuiper@vumc.nl RI Grunberg, Katrien/M-9715-2015 OI Grunberg, Katrien/0000-0003-1164-4365 NR 38 TC 4 Z9 4 U1 2 U2 5 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1525-7304 EI 1938-0690 J9 CLIN LUNG CANCER JI Clin. Lung Cancer PD JAN PY 2015 VL 16 IS 1 BP 60 EP 66 DI 10.1016/j.cllc.2014.07.008 PG 7 WC Oncology SC Oncology GA AW8CW UT WOS:000346489300010 PM 25242669 ER PT J AU Garshick, MK Kimball, AB AF Garshick, Marisa Kardos Kimball, Alexa Boer TI Psoriasis and the Life Cycle of Persistent Life Effects SO DERMATOLOGIC CLINICS LA English DT Article DE Psoriasis; Physical comorbidities; Psychological comorbidities; Stigma; Life effects ID QUALITY-OF-LIFE; POPULATION-BASED-COHORT; CHRONIC PLAQUE PSORIASIS; CORONARY-HEART-DISEASE; BODY-MASS INDEX; METABOLIC SYNDROME; FOLLOW-UP; RISK-FACTORS; MYOCARDIAL-INFARCTION; DIABETES-MELLITUS AB Psoriasis is associated with significant physical, social, and behavioral comorbidities that create a substantial burden. We outline herein that these comorbidities start early in life and persist for decades, ultimately impacting the entire life course of patients with psoriasis. By highlighting the ages that psoriasis patients are affected with physical, social, behavioral and emotional comorbidities, we demonstrate the age-appropriate considerations for psoriasis patients. C1 [Garshick, Marisa Kardos; Kimball, Alexa Boer] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 50 Staniford St,Suite 240, Boston, MA 02114 USA. EM akimball@mgh.harvard.edu FU Abbott; Centocor; Amgen FX Dr M.K. Garshick has no conflicts of interest to declare. Dr A.B. Kimball is an Investigator and Consultant and receives grants and honoraria from Abbott, Centocor, and Amgen. NR 155 TC 9 Z9 9 U1 0 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8635 EI 1558-0520 J9 DERMATOL CLIN JI Dermatol. Clin. PD JAN PY 2015 VL 33 IS 1 BP 25 EP + DI 10.1016/j.det.2014.09.003 PG 16 WC Dermatology SC Dermatology GA AW7QA UT WOS:000346458500004 PM 25412781 ER PT J AU Knowler, WC Edelstein, SL Goldberg, RB Ackermann, RT Crandall, JP Florez, JC Fowler, SE Herman, WH Horton, ES Kahn, SE Mather, KJ Nathan, DM AF Knowler, William C. Edelstein, Sharon L. Goldberg, Ronald B. Ackermann, Ronald T. Crandall, Jill P. Florez, Jose C. Fowler, Sarah E. Herman, William H. Horton, Edward S. Kahn, Steven E. Mather, Kieren J. Nathan, David M. CA Diabet Prevention Program Res Grp TI HbA(1c) as a Predictor of Diabetes and as an Outcome in the Diabetes Prevention Program: A Randomized Clinical Trial SO DIABETES CARE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE INTERVENTION; GLYCATED HEMOGLOBIN; EXPERT COMMITTEE; WEIGHT-LOSS; METFORMIN; RETINOPATHY; ADULTS; RISK; A1C AB OBJECTIVE Glycated hemoglobin (HbA(1c)), a standard measure of chronic glycemia for managing diabetes, has been proposed to diagnose diabetes and identify people at risk. The Diabetes Prevention Program (DPP) was a 3.2-year randomized clinical trial of preventing type 2 diabetes with a 10-year follow-up study, the DPP Outcomes Study (DPPOS). We evaluated baseline HbA(1c) as a predictor of diabetes and determined the effects of treatments on diabetes defined by an HbA(1c) >= 6.5% (48 mmol/mol). RESEARCH DESIGN AND METHODS We randomized 3,234 nondiabetic adults at high risk of diabetes to placebo, metformin, or intensive lifestyle intervention and followed them for the development of diabetes as diagnosed by fasting plasma glucose (FPG) and 2-h postload glucose (2hPG) concentrations (1997 American Diabetes Association [ADA] criteria). HbA(1c) was measured but not used for study eligibility or outcomes. We now evaluate treatment effects in the 2,765 participants who did not have diabetes at baseline according to FPG, 2hPG, or HbA(1c) (2010 ADA criteria). RESULTS Baseline HbA(1c) predicted incident diabetes in all treatment groups. Diabetes incidence defined by HbA(1c) >= 6.5% was reduced by 44% by metformin and 49% by lifestyle during the DPP and by 38% bymetformin and 29% by lifestyle throughout follow-up. Unlike the primary DPP and DPPOS findings based on glucose criteria, metformin and lifestyle were similarly effective in preventing diabetes defined by HbA(1c). CONCLUSIONS HbA(1c) predicted incident diabetes. In contrast to the superiority of the lifestyle intervention on glucose-defined diabetes, metformin and lifestyle interventions had similar effects in preventing HbA(1c)-defined diabetes. The long-term implications for other health outcomes remain to be determined. C1 [Knowler, William C.] NIDDK, Phoenix, AZ 85014 USA. [Edelstein, Sharon L.; Fowler, Sarah E.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Goldberg, Ronald B.] Univ Miami, Miami, FL USA. [Ackermann, Ronald T.] Northwestern Univ, Chicago, IL 60611 USA. [Crandall, Jill P.] Albert Einstein Coll Med, New York, NY USA. [Florez, Jose C.; Nathan, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Florez, Jose C.; Horton, Edward S.; Nathan, David M.] Harvard Univ, Sch Med, Boston, MA USA. [Herman, William H.] Univ Michigan, Ann Arbor, MI 48109 USA. [Horton, Edward S.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Mather, Kieren J.] Indiana Univ, Indianapolis, IN 46204 USA. RP Knowler, WC (reprint author), NIDDK, Phoenix, AZ 85014 USA. EM dppmail@bsc.gwu.edu OI Kahn, Steven/0000-0001-7307-9002 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health; NIDDK; Indian Health Service; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute on Aging; National Eye Institute; National Heart, Lung, and Blood Institute; Office of Research on Women's Health; National Institute on Minority Health and Health Disparities; Centers for Disease Control and Prevention; ADA FX During the DPPOS, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health provided funding to the clinical centers and the coordinating center for the design and conduct of the study and collection, management, analysis, and interpretation of the data. The Southwestern American Indian Centers were supported directly by the NIDDK, including its Intramural Research Program, and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources, supported data collection at many of the clinical centers. Funding was also provided by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the National Institute on Aging; the National Eye Institute; the National Heart, Lung, and Blood Institute; the Office of Research on Women's Health; the National Institute on Minority Health and Health Disparities; the Centers for Disease Control and Prevention; and the ADA. NR 30 TC 15 Z9 15 U1 2 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 2015 VL 38 IS 1 BP 51 EP 58 DI 10.2337/dc14-0886 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX2GT UT WOS:000346762300014 ER PT J AU Bjornstad, P Cree-Green, M Baumgartner, A Maahs, DM Cherney, DZ Pyle, L Regensteiner, JG Reusch, JE Nadeau, KJ AF Bjornstad, Petter Cree-Green, Melanie Baumgartner, Amy Maahs, David M. Cherney, David Z. Pyle, Laura Regensteiner, Judith G. Reusch, Jane E. Nadeau, Kristen J. TI Renal Function Is Associated With Peak Exercise Capacity in Adolescents With Type 1 Diabetes SO DIABETES CARE LA English DT Article ID CORONARY-ARTERY CALCIFICATION; GLOMERULAR-FILTRATION-RATE; EXCHANGE CLINIC REGISTRY; ALL-CAUSE MORTALITY; CARDIOVASCULAR-DISEASE; GENERAL-POPULATION; ENDOTHELIAL FUNCTION; INSULIN SENSITIVITY; RISK-FACTORS; HYPERFILTRATION AB OBJECTIVE Diabetic nephropathy and cardiovascular disease are strongly related in adults with type 1 diabetes, yet little is known about this relationship in adolescents prior to the onset of detectable clinical disease. We hypothesized that cardiopulmonary fitness would be directly associated with albumin-to-creatinine ratio (ACR) and inversely related to estimated glomerular filtration rate (eGFR) in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS Sixty-nine adolescents with type 1 diabetes and 13 nondiabetic control subjects of similar pubertal stage and BMI had insulin sensitivity (glucose infusion rate [GIR]), measured by hyperinsulinemic-euglycemic clamp, and lean body mass, measured by DEXA. Cardiopulmonary fitness was measured by cycle ergometry to obtain peak volume of oxygen (VO(2)peak), and renal function was measured by eGFR using the Bouvet equation (measuring creatinine and cystatin C levels) and ACR. RESULTS Adolescents (15.5 +/- 2.2 years of age) with type 1 diabetes (6.3 +/- 3.8 years diabetes duration) had reduced VO(2)peak (31.5 +/- 6.3 vs. 36.2 +/- 7.9 mL/kg . min, P = 0.046) and VO(2)peak/lean kg (43.7 +/- 7.0 vs. 51.068.6 mL/lean kg . min, P = 0.007) compared with nondiabetic control subjects. eGFR was inversely associated with VO(2)peak and VO(2)peak/lean kg after adjusting for sex, Tanner stage, GIR, HbA(1c\) level, systolic blood pressure, and LDL cholesterol level (beta +/- SE, VO(2)peak: 20.19 +/- 0.07, P = 0.02; VO(2)peak/lean kg: -0.19 +/- 0.09, P = 0.048). Moreover, participants in the highest tertile for eGFR had significantly lower sex-and Tanner-adjusted VO(2)peak and VO(2)peak/lean kg compared with participants in the lowest tertile. CONCLUSIONS Adolescents with type 1 diabetes had reduced exercise capacity, which was strongly associated with renal health, independent of insulin sensitivity. Future studies should examine the underlying interrelated pathophysiology in order to identify probable targets for treatment to reduce cardiovascular and renal complications. C1 [Bjornstad, Petter; Pyle, Laura] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO 80045 USA. [Cree-Green, Melanie; Baumgartner, Amy; Maahs, David M.; Nadeau, Kristen J.] Univ Colorado, Sch Med, Dept Pediat, Div Pediat Endocrinol, Aurora, CO USA. [Cree-Green, Melanie; Regensteiner, Judith G.; Reusch, Jane E.; Nadeau, Kristen J.] Univ Colorado, Sch Med, Ctr Womens Hlth Res, Aurora, CO USA. [Maahs, David M.] Univ Colorado, Sch Med, Barbara Davis Ctr Diabet, Aurora, CO USA. [Cherney, David Z.] Univ Toronto, Toronto Gen Hosp, Dept Med, Div Nephrol, Toronto, ON M5G 1L7, Canada. [Regensteiner, Judith G.] Univ Colorado, Sch Med, Dept Med, Div Internal Med, Aurora, CO USA. [Regensteiner, Judith G.] Univ Colorado, Sch Med, Div Cardiol, Aurora, CO USA. [Reusch, Jane E.] Denver VA Med Ctr, Dept Med, Div Internal Med, Denver, CO USA. RP Bjornstad, P (reprint author), Univ Colorado, Sch Med, Dept Pediat, Aurora, CO 80045 USA. EM petter.bjornstad@childrenscolorado.org OI Bjornstad, Petter/0000-0002-5160-2947 FU National Center for Research Resources [K23-RR-020038-01]; National Institutes of Health (NIH) [K12-5K12-HD-057022-04]; American Diabetes Association [7-11-CD-08, 1-11-JF-23]; JDRF [11-2010-343]; NIH-Department of Health and Human Services [R56-DK-088971]; NIH-National Center for Advancing Translational Sciences-Colorado Clinical and Translational Sciences Institute [UL1-TR-000154]; Center for Women's Health Research; U.S. Department of Veterans Affairs Merit Review Award FX Support for this study was provided by National Center for Research Resources grant K23-RR-020038-01, National Institutes of Health (NIH)-Building Interdisciplinary Research Careers in Women's Health grant K12-5K12-HD-057022-04, American Diabetes Association grants 7-11-CD-08 and 1-11-JF-23, JDRF Award 11-2010-343, NIH-Department of Health and Human Services grant R56-DK-088971, NIH-National Center for Advancing Translational Sciences-Colorado Clinical and Translational Sciences Institute grant UL1-TR-000154, the Center for Women's Health Research, and a U.S. Department of Veterans Affairs Merit Review Award. NR 40 TC 1 Z9 3 U1 1 U2 5 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 2015 VL 38 IS 1 BP 126 EP 131 DI 10.2337/dc14-1742 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX2GT UT WOS:000346762300024 PM 25414156 ER PT J AU Hsu, WC Araneta, MRG Kanaya, AM Chiang, JL Fujimoto, W AF Hsu, William C. Araneta, Maria Rosario G. Kanaya, Alka M. Chiang, Jane L. Fujimoto, Wilfred TI BMI Cut Points to Identify At-Risk Asian Americans for Type 2 Diabetes Screening SO DIABETES CARE LA English DT Article ID BODY-MASS INDEX; VISCERAL ADIPOSE-TISSUE; IMPAIRED GLUCOSE-TOLERANCE; NEW-YORK-CITY; JAPANESE-AMERICANS; PACIFIC ISLANDERS; WAIST CIRCUMFERENCE; METABOLIC SYNDROME; NATIVE HAWAIIANS; FAT DISTRIBUTION C1 [Hsu, William C.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Asian Amer Diabet Initiat, Boston, MA 02115 USA. [Araneta, Maria Rosario G.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Kanaya, Alka M.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. [Chiang, Jane L.] Amer Diabet Assoc, Alexandria, VA USA. [Fujimoto, Wilfred] Univ Washington, Dept Med, Seattle, WA USA. RP Hsu, WC (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Asian Amer Diabet Initiat, Boston, MA 02115 USA. EM william.hsu@joslin.harvard.edu FU NHLBI NIH HHS [K24 HL112827, R01 HL093009]; NIDDK NIH HHS [P30 DK063720] NR 47 TC 48 Z9 49 U1 0 U2 11 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 2015 VL 38 IS 1 BP 150 EP 158 DI 10.2337/dc14-2391 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX2GT UT WOS:000346762300027 PM 25538311 ER PT J AU Abrahamson, MJ AF Abrahamson, Martin J. TI Should Sulfonylureas Remain an Acceptable First-Line Add-on to Metformin Therapy in Patients With Type 2 Diabetes? Yes, They Continue to Serve Us Well! SO DIABETES CARE LA English DT Article ID GLUCOSE CONTROL; MELLITUS; COMPLICATIONS; HYPOGLYCEMIA; MANAGEMENT; SAFETY; METAANALYSIS; MONOTHERAPY; GLIMEPIRIDE; GLYBURIDE AB Since their introduction to clinical practice in the 1950s, sulfonylureas have been widely prescribed for use in patients with type 2 diabetes. Of all the other medications currently available for clinical use, only metformin has been used more frequently. However, several new drug classes have emerged that are reported to have equal glucose-lowering efficacy and greater safety when added to treatment of patients in whom metformin monotherapy is no longer sufficient. Moreover, current arguments also suggest that the alternative drugs may be superior to sulfonylureas with regard to the risk of cardiovascular complications. Thus, while there is universal agreement that metformin should remain the first-line pharmacologic therapy for those in whom lifestyle modification is insufficient to control hyperglycemia, there is no consensus as to which drug should be added to metformin. Therefore, given the current controversy, we provide a Point-Counterpoint on this issue. In the point narrative presented below, Dr. Abrahamson provides his argument suggesting that avoiding use of sulfonylureas as a class of medication as an add-on to metformin is not appropriate as there are many patients whose glycemic control would improve with use of these drugs with minimal risk of adverse events. In the following counterpoint narrative, Dr. Genuth suggests there is no longer a need for sulfonylureas to remain a first-line addition to metformin for those patients whose clinical characteristics are appropriate and whose health insurance and/or financial resources make an alternative drug affordable. -William T. Cefalu Editor in Chief, Diabetes Care C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Abrahamson, MJ (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. EM martin.abrahamson@joslin.harvard.edu NR 25 TC 8 Z9 9 U1 3 U2 12 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 2015 VL 38 IS 1 BP 166 EP 169 DI 10.2337/dc14-1945 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX2GT UT WOS:000346762300029 PM 25538313 ER PT J AU Fung, CH Igodan, U Alessi, C Martin, JL Dzierzewski, JM Josephson, K Kramer, BJ AF Fung, Constance H. Igodan, Uyi Alessi, Cathy Martin, Jennifer L. Dzierzewski, Joseph M. Josephson, Karen Kramer, B. Josea TI Human factors/usability barriers to home medical devices among individuals with disabling conditions: In-depth interviews with positive airway pressure device users SO DISABILITY AND HEALTH JOURNAL LA English DT Article DE Sleep apnea syndromes; Continuous positive airway pressure; Disabled persons; Equipment design ID SLEEP-APNEA SYNDROME; OLDER-ADULTS; EQUIPMENT AB Background: Evidence suggests that medical equipment often fails to accommodate the needs of individuals with disabling conditions. Few studies have focused on the accessibility of home medical devices such as positive airway pressure (PAP), which is a type of home medical equipment prescribed for long-term therapy. Objective: The purpose of this study was to explore in detail the types of difficulties experienced by patients with physical/sensory impairments who use PAP devices, as an initial step in designing a questionnaire to survey users about this topic. Methods: In this descriptive study, in-depth interviews were conducted with 19 participants (9 patients with physical/sensory impairment and 10 health care providers). Interviews were coded and analyzed for major topics. Results: Participants detailed the numerous ways in which current PAP devices fail to meet the needs of individuals with physical/sensory impairments (e.g., tremor, poor depth perception, paresis), by requiring patients to perform manually difficult tasks, such as inserting PAP parts through small apertures, attaching parts using a twisting motion, and lifting arms overhead to apply PAP headgear. These demands contributed to patients' frustration with and reduced usage of the home medical device. Conclusions: Our findings suggest that home medical devices such as PAP may not be currently designed to meet the needs of some users with physical/sensory impairments. Additional studies are needed to measure the prevalence and impact of impairment-related barriers on PAP adherence for this common medical equipment. Published by Elsevier Inc. C1 [Fung, Constance H.; Alessi, Cathy; Martin, Jennifer L.; Dzierzewski, Joseph M.; Kramer, B. Josea] Univ Calif Los Angeles, David Geffen Sch Med, North Hills, CA 91343 USA. [Fung, Constance H.; Igodan, Uyi; Alessi, Cathy; Martin, Jennifer L.; Dzierzewski, Joseph M.; Josephson, Karen; Kramer, B. Josea] VA Greater Los Angeles Healthcare Syst, Dept Vet Affairs, North Hills, CA 91343 USA. RP Fung, CH (reprint author), VA Greater Los Angeles Healthcare Syst, GRECC 11E,16111 Plummer St, North Hills, CA 91343 USA. EM Connie.Fung@va.gov FU American Sleep Medicine Foundation; Department of Veterans Affairs; Veterans Administration Greater Los Angeles Geriatric Research, Education and Clinical Center; American Federation for Aging Research; John A. Hartford Foundation FX Special thanks to Stella Jouldjian, MSW, MPH, for her data management support. This work was supported by the American Sleep Medicine Foundation Physician Scientist Training Award (to CHF), the Department of Veterans Affairs Advanced Geriatrics Fellowship Program (to CHF, JMD), Veterans Administration Greater Los Angeles Geriatric Research, Education and Clinical Center, American Federation for Aging Research (to CHF), the John A. Hartford Foundation (to CHF). NR 20 TC 2 Z9 2 U1 2 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-6574 EI 1876-7583 J9 DISABIL HEALTH J JI Disabil. Health J. PD JAN PY 2015 VL 8 IS 1 BP 86 EP 92 DI 10.1016/j.dhjo.2014.06.002 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health; Rehabilitation SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Rehabilitation GA AW2YZ UT WOS:000346153800012 PM 25126995 ER PT J AU Khawaja, RDA Singh, S Blake, M Harisinghani, M Choy, G Karosmangulu, A Padole, A Do, S Brown, K Thompson, R Morton, T Raihani, N Koehler, T Kalra, MK AF Khawaja, Ranish Deedar Ali Singh, Sarabjeet Blake, Michael Harisinghani, Mukesh Choy, Gary Karosmangulu, Ali Padole, Atul Do, Synho Brown, Kevin Thompson, Richard Morton, Thomas Raihani, Nilgoun Koehler, Thomas Kalra, Mannudeep K. TI Ultra-low dose abdominal MDCT: Using a knowledge-based Iterative Model Reconstruction technique for substantial dose reduction in a prospective clinical study SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE Radiation dose reduction; Abdominal MDCT; Iterative reconstruction technique ID FILTERED BACK-PROJECTION; CORONARY CT ANGIOGRAPHY; IMAGE-QUALITY; COMPUTED-TOMOGRAPHY; RADIATION-EXPOSURE; BODY CT; FEASIBILITY; SUMMIT AB Purpose: To assess lesion detection and image quality parameters of a knowledge-based Iterative Model Reconstruction (IMR) in reduced dose (RD) abdominal CT examinations. Materials and methods: This IRB-approved prospective study included 82 abdominal CT examinations performed for 41 consecutive patients (mean age, 62 +/- 12 years; F:M 28:13) who underwent a RD CT (SSDE, 1.5 mGy +/- 0.4 [similar to 0.9 mSv] at 120 kV with 17-20 mAs/slice) immediately after their standard dose (SD) CT exam (10 mGy +/- 3 [similar to 6 mSv] at 120 kV with automatic exposure control) on 256 MDCT (iCT, Philips Healthcare). SD data were reconstructed using filtered back projection (FBP). RD data were reconstructed with FBP and IMR. Four radiologists used a five-point scale (1 = image quality better than SD CT to 5 = image quality unacceptable) to assess both subjective image quality and artifacts. Lesions were first detected on RD FBP images. RD IMR and RD FBP images were then compared side-by-side to SD-FBP images in an independent, randomized and blinded fashion. Friedman's test and intraclass correlation coefficient were used for data analysis. Objective measurements included image noise and attenuation as well as noise spectral density (NSD) curves to assess the noise in frequency domain were obtained. In addition, a low-contrast phantom study was performed. Results: All true lesions (ranging from 32 to 55) on SD FBP images were detected on RD IMR images across all patients. RD FBP images were unacceptable for subjective image quality. Subjective ratings showed acceptable image quality for IMR for organ margins, soft-tissue structures, and retroperitoneal lymphadenopathy, compared to RD FBP in patients with a BMI <= 25 kg/m(2) (median-range, 2-3). Irrespective of patient BMI, subjective ratings for hepatic/renal cysts, stones and colonic diverticula were significantly better with RD IMR images (P< 0.01). Objective image noise for RD FBP was 57-66% higher, and for RD IMR was 8-56% lower than that for SD-FBP (P< 0.01). NSD showed significantly lower noise in the frequency domain with IMR in all patients compared to FBP. Conclusion: IMR considerably improved both objective and subjective image quality parameters of RD abdominal CT images compared to FBP in patients with BMI less than or equal to 25 kg/m(2). (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Khawaja, Ranish Deedar Ali; Singh, Sarabjeet; Blake, Michael; Harisinghani, Mukesh; Choy, Gary; Karosmangulu, Ali; Padole, Atul; Do, Synho; Kalra, Mannudeep K.] Massachusetts Gen Hosp, MGH Imaging, Boston, MA 02114 USA. [Khawaja, Ranish Deedar Ali; Singh, Sarabjeet; Blake, Michael; Harisinghani, Mukesh; Choy, Gary; Karosmangulu, Ali; Padole, Atul; Do, Synho; Kalra, Mannudeep K.] Harvard Univ, Sch Med, Boston, MA USA. [Brown, Kevin; Thompson, Richard; Morton, Thomas; Raihani, Nilgoun] Philips Healthcare, CT Res & Adv Dev, Cleveland, OH USA. [Koehler, Thomas] Philips Technol GmbH, Innovat Technol, Hamburg, Germany. RP Khawaja, RDA (reprint author), 25 New Chardon St,4th Floor, Boston, MA 02114 USA. EM rkhawaja@mgh.harvard.edu FU Radiological Society of North America (RSNA); GE Healthcare; Philips Healthcare; Toshiba America Systems FX Co-author Sarabjeet Singh M.D. received research funding from the Radiological Society of North America (RSNA), GE Healthcare, Philips Healthcare, and Toshiba America Systems. Coauthor Synho Do Ph.D. received research funding from Philips Healthcare. Coauthors Kevin Brown, Richard Thompson, Thomas Morton, Nilgoun Raihani and Thomas Koehler are employees of Philips Healthcare. The rest of the co-authors have no conflict of interests and financial disclosures. NR 31 TC 13 Z9 13 U1 0 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X EI 1872-7727 J9 EUR J RADIOL JI Eur. J. Radiol. PD JAN PY 2015 VL 84 IS 1 BP 2 EP 10 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AW6NL UT WOS:000346386100001 PM 25458225 ER PT J AU Ananthakrishnan, AN Hanauer, SB AF Ananthakrishnan, Ashwin N. Hanauer, Stephen B. TI The Holy Grail, or Only Half Way There? SO GASTROENTEROLOGY LA English DT Editorial Material ID CROHNS-DISEASE; SEVERITY; INDEX C1 [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.] Harvard Univ, Sch Med, Boston, MA USA. [Hanauer, Stephen B.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@mgh.harvard.edu FU NIDDK NIH HHS [K23 DK097142] NR 12 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2015 VL 148 IS 1 BP 8 EP 10 DI 10.1053/j.gastro.2014.11.022 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AW9LT UT WOS:000346579500008 PM 25451664 ER PT J AU Curry, MP Forns, X Chung, RT Terrault, NA Brown, R Fenkel, JM Gordon, F O'Leary, J Kuo, A Schiano, T Everson, G Schiff, E Befeler, A Gane, E Saab, S McHutchison, JG Subramanian, GM Symonds, WT Denning, J McNair, L Arterburn, S Svarovskaia, E Moonka, D Afdhal, N AF Curry, Michael P. Forns, Xavier Chung, Raymond T. Terrault, Norah A. Brown, Robert, Jr. Fenkel, Jonathan M. Gordon, Fredric O'Leary, Jacqueline Kuo, Alexander Schiano, Thomas Everson, Gregory Schiff, Eugene Befeler, Alex Gane, Edward Saab, Sammy McHutchison, John G. Subramanian, G. Mani Symonds, William T. Denning, Jill McNair, Lindsay Arterburn, Sarah Svarovskaia, Evguenia Moonka, Dilip Afdhal, Nezam TI Sofosbuvir and Ribavirin Prevent Recurrence of HCV Infection After Liver Transplantation: An Open-Label Study SO GASTROENTEROLOGY LA English DT Article DE Hepatitis C Virus; Liver Transplantation; HCV Recurrence; Direct-Acting Antiviral Agents ID TREATMENT-NAIVE PATIENTS; HEPATITIS-C INFECTION; ANTIVIRAL THERAPY; PHASE-2 TRIAL; KINETICS; TOLERABILITY; CIRRHOSIS; ALPHA-2A; FUTURE; CELLS AB BACKGROUND & AIMS: Patients with detectable hepatitis C virus (HCV) RNA at the time of liver transplantation universally experience recurrent HCV infection. Antiviral treatment before transplantation can prevent HCV recurrence, but existing interferon-based regimens are poorly tolerated and are either ineffective or contraindicated in most patients. We performed a trial to determine whether sofosbuvir and ribavirin treatment before liver transplantation could prevent HCV recurrence afterward. METHODS: In a phase 2, open-label study, 61 patients with HCV of any genotype and cirrhosis (Child-Turcotte-Pugh score, <= 7) who were on waitlists for liver transplantation for hepatocellular carcinoma, received up to 48 weeks of sofosbuvir (400 mg) and ribavirin before liver transplantation. The primary end point was the proportion of patients with HCV-RNA levels less than 25 IU/mL at 12 weeks after transplantation among patients with this HCV-RNA level at their last measurement before transplantation. RESULTS: Sixty-one patients received sofosbuvir and ribavirin, and 46 received transplanted livers. The per-protocol efficacy population consisted of 43 patients who had HCV-RNA level less than 25 IU/mL at the time of transplantation. Of these 43 patients, 30 (70%) had a post-transplantation virologic response at 12 weeks, 10 (23%) had recurrent infection, and 3 (7%) died (2 from non-function of the primary graft and 1 from complications of hepatic artery thrombosis). Of all 61 patients given sofosbuvir and ribavirin, 49% had a post-transplantation virologic response. Recurrence was related inversely to the number of consecutive days of undetectable HCV RNA before transplantation. The most frequently reported adverse events were fatigue (in 38% of patients), headache (23%), and anemia (21%). CONCLUSIONS: Administration of sofosbuvir and ribavirin before liver transplantation can prevent post-transplant HCV recurrence. ClinicalTrials.gov: NCT01559844. C1 [Curry, Michael P.; Afdhal, Nezam] Beth Israel Deaconess Med Ctr, Transplant Inst, Boston, MA 02215 USA. [Forns, Xavier] Inst Invest Biomed August Pi & Sunyer, Liver Unit, Hosp Clin, Barcelona, Spain. [Forns, Xavier] Ctr Invest Biomed Red Enfermedades Hepat & Digest, Barcelona, Spain. [Chung, Raymond T.] Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. [Terrault, Norah A.] Univ Calif San Francisco, Div Gastroenterol, San Francisco, CA 94143 USA. [Brown, Robert, Jr.] Columbia Univ, Ctr Liver Dis & Transplantat, New York, NY USA. [Fenkel, Jonathan M.] Thomas Jefferson Univ Hosp, Div Gastroenterol & Hepatol, Philadelphia, PA 19107 USA. [Gordon, Fredric] Lahey Clin Fdn, Burlington, MA USA. [O'Leary, Jacqueline] Baylor Univ, Med Ctr, Dallas, TX USA. [Kuo, Alexander] Univ Calif San Diego, La Jolla, CA 92093 USA. [Schiano, Thomas] Mt Sinai Sch Med, New York, NY USA. [Everson, Gregory] Univ Colorado, Sect Hepatol, Denver, CO 80202 USA. [Schiff, Eugene] Univ Miami, Ctr Liver Dis, Miami, FL USA. [Befeler, Alex] St Louis Univ, Div Gastroenterol & Hepatol, St Louis, MO 63103 USA. [Gane, Edward] Auckland City Hosp, New Zealand Liver Transplant Unit, Auckland, New Zealand. [Saab, Sammy] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [McHutchison, John G.; Subramanian, G. Mani; Symonds, William T.; Denning, Jill; McNair, Lindsay; Arterburn, Sarah; Svarovskaia, Evguenia] Gilead Sci Inc, Foster City, CA 94404 USA. [Moonka, Dilip] Henry Ford Hlth Syst, Gastroenterol, Detroit, MI USA. RP Curry, MP (reprint author), Beth Israel Deaconess Med Ctr, 110 Francis St,Suite 7, Boston, MA 02215 USA. EM mcurry@bidmc.harvard.edu OI Kuo, Alexander/0000-0002-9106-8865 FU Gilead Sciences FX Supported by Gilead Sciences. NR 30 TC 119 Z9 120 U1 3 U2 20 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2015 VL 148 IS 1 BP 100 EP U519 DI 10.1053/j.gastro.2014.09.023 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AW9LT UT WOS:000346579500023 PM 25261839 ER PT J AU Chen, P Torralba, M Tan, J Embree, M Zengler, K Starkel, P van Pijkeren, JP DePew, J Loomba, R Ho, SB Bajaj, JS Mutlu, EA Keshavarzian, A Tsukamoto, H Nelson, KE Fouts, DE Schnabl, B AF Chen, Peng Torralba, Manolito Tan, Justin Embree, Mallory Zengler, Karsten Starkel, Peter van Pijkeren, Jan-Peter DePew, Jessica Loomba, Rohit Ho, Samuel B. Bajaj, Jasmohan S. Mutlu, Ece A. Keshavarzian, Ali Tsukamoto, Hidekazu Nelson, Karen E. Fouts, Derrick E. Schnabl, Bernd TI Supplementation of Saturated Long-Chain Fatty Acids Maintains Intestinal Eubiosis and Reduces Ethanol-induced Liver Injury in Mice SO GASTROENTEROLOGY LA English DT Article DE Metagenomics; Metabolomics; Microbiome; Microbiota ID LACTOBACILLUS-RHAMNOSUS GG; PARACELLULAR PERMEABILITY; ALCOHOLIC STEATOHEPATITIS; POSSIBLE MECHANISM; RAT MODEL; DISEASE; GUT; INFLAMMATION; ENDOTOXEMIA; MICROBIOME AB BACKGROUND & AIMS: Alcoholic liver disease is a leading cause of mortality. Chronic alcohol consumption is accompanied by intestinal dysbiosis, and development of alcoholic liver disease requires gut-derived bacterial products. However, little is known about how alterations to the microbiome contribute to pathogenesis of alcoholic liver disease. METHODS: We used the Tsukamoto-French mouse model, which involves continuous intragastric feeding of isocaloric diet or alcohol for 3 weeks. Bacterial DNA from the cecum was extracted for deep metagenomic sequencing. Targeted metabolomics assessed concentrations of saturated fatty acids in cecal contents. To maintain intestinal metabolic homeostasis, diets of ethanol-fed and control mice were supplemented with saturated long-chain fatty acids (LCFA). Bacterial genes involved in fatty acid biosynthesis, amounts of lactobacilli, and saturated LCFA were measured in fecal samples of nonalcoholic individuals and patients with active alcohol abuse. RESULTS: Analyses of intestinal contents from mice revealed alcohol-associated changes to the intestinal metagenome and metabolome, characterized by reduced synthesis of saturated LCFA. Maintaining intestinal levels of saturated fatty acids in mice resulted in eubiosis, stabilized the intestinal gut barrier, and reduced ethanol-induced liver injury. Saturated LCFA are metabolized by commensal Lactobacillus and promote their growth. Proportions of bacterial genes involved in fatty acid biosynthesis were lower in feces from patients with active alcohol abuse than controls. Total levels of LCFA correlated with those of lactobacilli in fecal samples from patients with active alcohol abuse but not in controls. CONCLUSIONS: In humans and mice, alcohol causes intestinal dysbiosis, reducing the capacity of the microbiome to synthesize saturated LCFA and the proportion of Lactobacillus species. Dietary approaches to restore levels of saturated fatty acids in the intestine might reduce ethanolinduced liver injury in patients with alcoholic liver disease. C1 [Chen, Peng; Loomba, Rohit; Ho, Samuel B.; Schnabl, Bernd] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Torralba, Manolito; DePew, Jessica; Nelson, Karen E.; Fouts, Derrick E.] J Craig Venter Inst, Rockville, MD USA. [Tan, Justin; Embree, Mallory; Zengler, Karsten] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. [Starkel, Peter] Catholic Univ Louvain, St Luc Univ Hosp, B-1200 Brussels, Belgium. [van Pijkeren, Jan-Peter] Univ Wisconsin, Dept Food Sci, Madison, WI 53706 USA. [Ho, Samuel B.] VA San Diego Healthcare Syst, Dept Med, San Diego, CA USA. [Bajaj, Jasmohan S.] Virginia Commonwealth Univ, Div Gastroenterol Hepatol & Nutr, Richmond, VA USA. [Bajaj, Jasmohan S.] McGuire VA Med Ctr, Richmond, VA USA. [Mutlu, Ece A.; Keshavarzian, Ali] Rush Univ, Med Ctr, Dept Med, Chicago, IL 60612 USA. [Tsukamoto, Hidekazu] Univ So Calif, Greater Los Angeles VA Healthcare Syst, Southern Calif Res Ctr Alcohol Liver & Pancreat D, Dept Pathol,Keck Sch Med, Los Angeles, CA 90033 USA. RP Schnabl, B (reprint author), Univ Calif San Diego, Dept Med, MC0063,9500 Gilman Dr, La Jolla, CA 92093 USA. EM beschnabl@ucsd.edu OI Zengler, Karsten/0000-0002-8062-3296 FU National Institutes of Health (NIH) [K08 DK081830, R01 AA020703, U01 AA021856]; ABMRF/The Foundation for Alcohol Research; American Gastroenterological Association Foundation-Sucampo-ASP Designated Research Award in Geriatric Gastroenterology; T. Franklin Williams Scholarship Award; Atlantic Philanthropies, Inc; John A. Hartford Foundation; Association of Specialty Professors; NIH [R01AA020216, RC2AA019405, R01 AA020203, DK097153]; National Institute on Alcohol Abuse and Alcoholism [P50AA011999]; [K23-DK090303] FX This study was supported in part by National Institutes of Health (NIH) grants K08 DK081830, R01 AA020703, U01 AA021856 and by ABMRF/The Foundation for Alcohol Research (to Bernd Schnabl). Rohit Loomba is supported in part by the American Gastroenterological Association Foundation-Sucampo-ASP Designated Research Award in Geriatric Gastroenterology, a T. Franklin Williams Scholarship Award, Atlantic Philanthropies, Inc, the John A. Hartford Foundation, the Association of Specialty Professors, and grant K23-DK090303. Ali Keshavarzian received support from NIH grants R01AA020216 and RC2AA019405. Jasmohan S. Bajaj is supported by NIH grant R01 AA020203. Animal studies at the Animal Core facility, Southern California Research Center for Alcoholic Liver and Pancreatic Diseases and Cirrhosis, University of Southern California were funded by the National Institute on Alcohol Abuse and Alcoholism (P50AA011999). This work utilized Core Services supported by grant DK097153 of NIH to the University of Michigan. NR 57 TC 39 Z9 42 U1 10 U2 51 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2015 VL 148 IS 1 BP 203 EP U345 DI 10.1053/j.gastro.2014.09.014 PG 28 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AW9LT UT WOS:000346579500033 PM 25239591 ER PT J AU Reddy, KR Beavers, KL Hammond, SP Lim, JK Falck-Ytter, YT AF Reddy, K. Rajender Beavers, Kimberly L. Hammond, Sarah P. Lim, Joseph K. Falck-Ytter, Yngve T. TI American Gastroenterological Association Institute Guideline on the Prevention and Treatment of Hepatitis B Virus Reactivation During Immunosuppressive Drug Therapy SO GASTROENTEROLOGY LA English DT Article C1 [Reddy, K. Rajender] Univ Penn, Div Gastroenterol & Hepatol, Philadelphia, PA 19104 USA. [Beavers, Kimberly L.] Med Univ S Carolina, Div Gastroenterol & Hepatol, Charleston, SC 29425 USA. [Hammond, Sarah P.] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Infect Dis, Boston, MA 02115 USA. [Hammond, Sarah P.] Harvard Univ, Sch Med, Boston, MA USA. [Lim, Joseph K.] Yale Univ, Sch Med, Div Gastroenterol & Hepatol, New Haven, CT USA. [Falck-Ytter, Yngve T.] Case Western Reserve Univ, Dept Med, Div Gastroenterol & Hepatol, Case & VA Med Ctr, Cleveland, OH 44106 USA. RP Reddy, KR (reprint author), AGA Natl Off, Clin Practice & Qual Management Comm, 4930 Del Ray Ave, Bethesda, MD 20814 USA. EM msiedler@gastro.org RI Nguyen, Geoffrey/C-4614-2015 OI Nguyen, Geoffrey/0000-0001-7083-7429 NR 4 TC 56 Z9 59 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2015 VL 148 IS 1 BP 215 EP U351 DI 10.1053/j.gastro.2014.10.039 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AW9LT UT WOS:000346579500034 PM 25447850 ER PT J AU Sung, JJY Ng, SC Chan, FKL Chiu, HM Kim, HS Matsuda, T Ng, SSM Lau, JYW Zheng, S Adler, S Reddy, N Yeoh, KG Tsoi, KKF Ching, JYL Kuipers, EJ Rabeneck, L Young, GP Steele, RJ Lieberman, D Goh, KL AF Sung, J. J. Y. Ng, S. C. Chan, F. K. L. Chiu, H. M. Kim, H. S. Matsuda, T. Ng, S. S. M. Lau, J. Y. W. Zheng, S. Adler, S. Reddy, N. Yeoh, K. G. Tsoi, K. K. F. Ching, J. Y. L. Kuipers, E. J. Rabeneck, L. Young, G. P. Steele, R. J. Lieberman, D. Goh, K. L. TI An updated Asia Pacific Consensus Recommendations on colorectal cancer screening SO GUT LA English DT Article ID OCCULT BLOOD-TEST; RANDOMIZED-CONTROLLED-TRIAL; ADENOMA DETECTION RATE; SOCIETY-TASK-FORCE; FECAL IMMUNOCHEMICAL TEST; AVERAGE-RISK CHINESE; BODY-MASS INDEX; CT-COLONOGRAPHY; ADVANCED NEOPLASIA; FAMILY-HISTORY AB Objective Since the publication of the first Asia Pacific Consensus on Colorectal Cancer (CRC) in 2008, there are substantial advancements in the science and experience of implementing CRC screening. The Asia Pacific Working Group aimed to provide an updated set of consensus recommendations. Design Members from 14 Asian regions gathered to seek consensus using other national and international guidelines, and recent relevant literature published from 2008 to 2013. A modified Delphi process was adopted to develop the statements. Results Age range for CRC screening is defined as 5075 years. Advancing age, male, family history of CRC, smoking and obesity are confirmed risk factors for CRC and advanced neoplasia. A risk-stratified scoring system is recommended for selecting high-risk patients for colonoscopy. Quantitative faecal immunochemical test (FIT) instead of guaiac-based faecal occult blood test (gFOBT) is preferred for average-risk subjects. Ancillary methods in colonoscopy, with the exception of chromoendoscopy, have not proven to be superior to high-definition white light endoscopy in identifying adenoma. Quality of colonoscopy should be upheld and quality assurance programme should be in place to audit every aspects of CRC screening. Serrated adenoma is recognised as a risk for interval cancer. There is no consensus on the recruitment of trained endoscopy nurses for CRC screening. Conclusions Based on recent data on CRC screening, an updated list of recommendations on CRC screening is prepared. These consensus statements will further enhance the implementation of CRC screening in the Asia Pacific region. C1 [Sung, J. J. Y.; Ng, S. C.; Chan, F. K. L.] Chinese Univ Hong Kong, Inst Digest Dis, Shatin, Hong Kong, Peoples R China. [Ng, S. C.; Chan, F. K. L.; Ching, J. Y. L.] Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China. [Chiu, H. M.] Natl Taiwan Univ, Coll Med, Dept Internal Med, Taipei, Taiwan. [Kim, H. S.] Yonsei Univ, Wonju Coll Med, Dept Internal Med, Wonju, South Korea. [Matsuda, T.] Natl Canc Ctr, Endoscopy Div, Tokyo, Japan. [Ng, S. S. M.; Lau, J. Y. W.] Chinese Univ Hong Kong, Dept Surg, Hong Kong, Hong Kong, Peoples R China. [Zheng, S.] Zhejiang Univ, Canc Inst, Hanggzhou, Zhejiang, Peoples R China. [Adler, S.] Bikur Holim Hosp, Div Gastroenterol, Jerusalem, Israel. [Reddy, N.] Asian Healthcare Fdn, Asian Inst Gastroenterol, Hyderabad, Andhra Pradesh, India. [Yeoh, K. G.] Natl Univ Singapore, Asian Healthcare Fdn, Dept Med, Singapore 117548, Singapore. [Tsoi, K. K. F.] Chinese Univ Hong Kong, Sch Publ Hlth & Primary Care, Hong Kong, Hong Kong, Peoples R China. [Kuipers, E. J.] Erasmus Univ, Med Ctr, Dept Med & Therapeut, Rotterdam, Netherlands. [Rabeneck, L.] Univ Toronto, Inst Clin Evaluat Sci, Toronto, ON M5S 1A1, Canada. [Young, G. P.] Flinders Med Ctr, Dept Gastroenterol, Adelaide, SA, Australia. [Steele, R. J.] Univ Dundee, Dept Surg & Mol Oncol, Dundee, Scotland. [Lieberman, D.] Portland VA Med Ctr, Portland, OR USA. [Goh, K. L.] Univ Malaya, Dept Gastroenterol & Hepatol, Kuala Lumpur, Malaysia. RP Sung, JJY (reprint author), Chinese Univ Hong Kong, Inst Digest Dis, Shatin, Hong Kong, Peoples R China. EM jjysung@cuhk.edu.hk RI Goh, Khean-Lee/B-6404-2009; Ng, Siew Chien/N-4733-2015; Chan, Francis K. L./F-4851-2010; OI Ng, Siew Chien/0000-0002-6850-4454; Chan, Francis K. L./0000-0001-7388-2436; CHIU, HAN-MO/0000-0003-2786-8056 FU Olympus Medical System Corporation; Given Imaging FX An unrestricted education grant was received from Olympus Medical System Corporation and Given Imaging. In order to avoid conflict of interest, industrial partners were not allowed to provide input for the statements, add references in the literature search, participate in the discussion and vote in the consensus conference. None of the sponsors contributed towards the development of the consensus statements or in their voting. NR 123 TC 57 Z9 61 U1 4 U2 17 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD JAN PY 2015 VL 64 IS 1 BP 121 EP 132 DI 10.1136/gutjnl-2013-306503 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AW3EE UT WOS:000346167700017 PM 24647008 ER PT J AU Wu, BU Pandol, SJ Liu, ILA AF Wu, Bechien U. Pandol, Stephen J. Liu, In-Lu Amy TI Simvastatin is associated with reduced risk of acute pancreatitis: findings from a regional integrated healthcare system SO GUT LA English DT Article ID STATINS; THERAPY AB Objective To characterise the relationship between simvastatin and risk of acute pancreatitis (AP). Design We conducted a retrospective cohort study (2006-2012) on data from an integrated healthcare system in southern California. Exposure to simvastatin was calculated from time of initial dispensation until 60 days following prescription termination. AP cases were defined by ICD-9 CM 577.0 and serum lipase >= 3 times normal. Patients were censored at death, last follow-up, and onset of AP or end-of-study. Incidence rate of pancreatitis among simvastatin users was compared with the adult reference population. Robust Poisson regression was used to generate risk ratio (RR) estimates for simvastatin use adjusted for age, gender, race/ethnicity, gallstone-related disorders, hypertriglyceridaemia, smoking and alcohol dependence. Analysis was repeated for atorvastatin. Results Among 3 967 859 adult patients (median duration of follow-up of 3.4 years), 6399 developed an initial episode of AP. A total of 707 236 patients received simvastatin during the study period. Patients that received simvastatin were more likely to have gallstone-related disorders, alcohol dependence or hypertriglyceridaemia compared with the reference population. Nevertheless, risk of AP was significantly reduced with simvastatin use, crude incidence rate ratio 0.626 (95% CL 0.588, 0.668), p<0.0001. In multivariate analysis, simvastatin was independently associated with reduced risk of pancreatitis, adjusted RR 0.29 (95% CL 0.27, 0.31) after adjusting for age, gender, race/ethnicity, gallstone disorders, alcohol dependence, smoking and hypertriglyceridaemia. Similar results were noted with atorvastatin, adjusted RR 0.33 (0.29, 0.38). Conclusions Use of simvastatin was independently associated with reduced risk of AP in this integrated healthcare setting. Similar findings for atorvastatin suggest a possible class effect. C1 [Wu, Bechien U.] W Los Angeles Vet Affairs Med Ctr, Kaiser Permanente, So Calif Permanente Med Grp, Div Gastroenterol,Ctr Pancreat Care, Los Angeles, CA 90027 USA. [Pandol, Stephen J.] Cedars Sinai Med Ctr, Program Basic & Translat Pancreat Res, Los Angeles, CA 90048 USA. [Liu, In-Lu Amy] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA 91101 USA. RP Wu, BU (reprint author), W Los Angeles Vet Affairs Med Ctr, Kaiser Permanente, Div Gastroenterol, Ctr Pancreat Care, 1526 North Edgemont Ave, Los Angeles, CA 90027 USA. EM Bechien.u.wu@kp.org FU BLRD VA [I01 BX001484]; NCI NIH HHS [P01 CA163200]; NIAAA NIH HHS [P50 AA011999]; NIDDK NIH HHS [P01 DK098108] NR 16 TC 7 Z9 8 U1 1 U2 5 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD JAN PY 2015 VL 64 IS 1 BP 133 EP 138 DI 10.1136/gutjnl-2013-306564 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AW3EE UT WOS:000346167700018 PM 24742713 ER PT J AU Piantoni, G Van der Werf, YD Jensen, O Van Someren, EJW AF Piantoni, Giovanni Van der Werf, Ysbrand D. Jensen, Ole Van Someren, Eus J. W. TI Memory Traces of Long-Range Coordinated Oscillations in the Sleeping Human Brain SO HUMAN BRAIN MAPPING LA English DT Article DE learning; memory; plasticity; neuronal network reorganization; oscillations; reactivation; sleep; magnetoencephalography ID FUNCTIONAL NEUROIMAGING INSIGHTS; SLOW-WAVE SLEEP; PREFRONTAL CORTEX; NEURONAL SYNCHRONIZATION; DEPENDENT CHANGES; BETA-RHYTHMS; MU-RHYTHMS; REM-SLEEP; REACTIVATION; EEG AB Cognition involves coordinated activity across distributed neuronal networks. Neuronal activity during learning triggers cortical plasticity that allows for reorganization of the neuronal network and integration of new information. Animal studies have shown post-learning reactivation of learning-elicited neuronal network activity during subsequent sleep, supporting consolidation of the reorganization. However, no previous studies, to our knowledge, have demonstrated reactivation of specific learning-elicited long-range functional connectivity during sleep in humans. We here show reactivation of learning-induced long-range synchronization of magnetoencephalography power fluctuations in human sleep. Visuomotor learning elicited a specific profile of long-range cortico-cortical synchronization of slow (0.1 Hz) fluctuations in beta band (12-30 Hz) power. The parieto-occipital part of this synchronization profile reappeared in delta band (1-3.5 Hz) power fluctuations during subsequent sleep, but not during the intervening wakefulness period. Individual differences in the reactivated synchronization predicted postsleep performance improvement. The presleep resting-state synchronization profile was not reactivated during sleep. The findings demonstrate reactivation of long-range coordination of neuronal activity in humans, more specifically of reactivation of coupling of infra-slow fluctuations in oscillatory power. The spatiotemporal profile of delta power fluctuations during sleep may subserve memory consolidation by echoing coordinated activation elicited by prior learning. Hum Brain Mapp, 36:67-84, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [Piantoni, Giovanni; Van der Werf, Ysbrand D.; Van Someren, Eus J. W.] Netherlands Inst Neurosci, Dept Sleep & Cognit, NL-1105 BA Amsterdam, Netherlands. [Piantoni, Giovanni] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Van der Werf, Ysbrand D.] Vrije Univ Amsterdam, Med Ctr, Dept Anat & Neurosci, Amsterdam, Netherlands. [Jensen, Ole] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands. [Van Someren, Eus J. W.] Vrije Univ Amsterdam, CNCR, Dept Integrat Neurophysiol, Amsterdam, Netherlands. [Van Someren, Eus J. W.] Vrije Univ Amsterdam, Med Ctr, Dept Med Psychol, Amsterdam, Netherlands. RP Piantoni, G (reprint author), Netherlands Inst Neurosci, Dept Sleep & Cognit, Meibergdreef 47, NL-1105 BA Amsterdam, Netherlands. EM gio@gpiantoni.com OI Piantoni, Giovanni/0000-0002-5308-926X FU NWO Cognition Integrated Research Project [051.04.010]; VICI [453.07.001]; NWO VIDI [016.095.359] FX Contract grant sponsor: NWO Cognition Integrated Research Project (to E.J.W.V.S.); Contract grant number: 051.04.010; Contract grant sponsor: VICI (to E.J.W.V.S.); Contract grant number: 453.07.001; Contract grant sponsor: NWO VIDI (to Y.D.v.d.W); Contract grant number: 016.095.359. NR 89 TC 3 Z9 3 U1 0 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD JAN PY 2015 VL 36 IS 1 BP 67 EP 84 DI 10.1002/hbm.22613 PG 18 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AW3ML UT WOS:000346190800006 PM 25139521 ER PT J AU Taylor, PA Jacobson, SW van der Kouwe, A Molteno, CD Chen, G Wintermark, P Alhamud, A Jacobson, JL Meintjes, EM AF Taylor, Paul A. Jacobson, Sandra W. van der Kouwe, Andre Molteno, Christopher D. Chen, Gang Wintermark, Pia Alhamud, Alkathafi Jacobson, Joseph L. Meintjes, Ernesta M. TI A DTI-Based Tractography Study of Effects on Brain Structure Associated with Prenatal Alcohol Exposure in Newborns SO HUMAN BRAIN MAPPING LA English DT Article DE diffusion tensor imaging; tractography; prenatal alcohol exposure; newborns; white matter ID MYELIN BASIC-PROTEIN; WHITE-MATTER MICROSTRUCTURE; SPECTRUM DISORDERS; YOUNG-ADULTS; DIFFUSION; CHILDREN; MATURATION; CHILDHOOD; MRI; EXPRESSION AB Prenatal alcohol exposure (PAE) is known to have severe, long-term consequences for brain and behavioral development already detectable in infancy and childhood. Resulting features of fetal alcohol spectrum disorders include cognitive and behavioral effects, as well as facial anomalies and growth deficits. Diffusion tensor imaging (DTI) and tractography were used to analyze white matter (WM) development in 11 newborns (age since conception <45 weeks) whose mothers were recruited during pregnancy. Comparisons were made with nine age-matched controls born to abstainers or light drinkers from the same Cape Coloured (mixed ancestry) community near Cape Town, South Africa. DTI parameters, T1 relaxation time, proton density and volumes were used to quantify and investigate group differences in WM in the newborn brains. Probabilistic tractography was used to estimate and to delineate similar tract locations among the subjects for transcallosal pathways, cortico-spinal projection fibers, and cortico-cortical association fibers. In each of these WM networks, the axial diffusivity was the parameter that showed the strongest association with maternal drinking. The strongest relations were observed in medial and inferior WM, regions in which the myelination process typically begins. In contrast to studies of older individuals with PAE, fractional anisotropy did not exhibit a consistent and significant relation with alcohol exposure. To our knowledge, this is the first DTI-tractography study of prenatally alcohol exposed newborns. Hum Brain Mapp, 36:170-186, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [Taylor, Paul A.; Jacobson, Sandra W.; Alhamud, Alkathafi; Jacobson, Joseph L.; Meintjes, Ernesta M.] Univ Cape Town, Fac Hlth Sci, Dept Human Biol, ZA-7925 Cape Town, South Africa. [Taylor, Paul A.; Alhamud, Alkathafi; Meintjes, Ernesta M.] Univ Cape Town, Fac Hlth Sci, MRC UCT Med Imaging Res Unit, ZA-7925 Cape Town, South Africa. [Taylor, Paul A.] African Inst Math Sci, Muizenberg, Western Cape, South Africa. [Jacobson, Sandra W.; Jacobson, Joseph L.] Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI 48201 USA. [Jacobson, Sandra W.; Molteno, Christopher D.; Jacobson, Joseph L.] Univ Cape Town, Dept Psychiat & Mental Hlth, ZA-7925 Cape Town, South Africa. [van der Kouwe, Andre] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Chen, Gang] NIMH, Sci & Stat Comp Core, NIH, Bethesda, MD 20892 USA. [Wintermark, Pia] Montreal Childrens Hosp, Montreal, PQ H3H 1P3, Canada. RP Taylor, PA (reprint author), Univ Cape Town, Fac Hlth Sci, Dept Human Biol, ZA-7925 Cape Town, South Africa. EM neon.taylor@gmail.com; sandra.jacobson@wayne.edu FU National Institute on Alcohol Abuse and Alcoholism [R01-AA016781, R21-AA020037]; FIC; NIAAA Grant [R21-AA017410]; NIMH Grant [R21MH096559]; NRF/DST South African Research Chairs Initiative; South African Medical Research Council; State of Michigan FX Contract grant sponsor: National Institute on Alcohol Abuse and Alcoholism; Contract grant number: R01-AA016781 (to S.J.); Contract grant sponsor: National Institute on Alcohol Abuse and Alcoholism; Contract grant number: R21-AA020037 (to S.J., E.M., and A.v.d.K.); Contract grant sponsor: FIC; Contract grant sponsor: NIAAA Grant; Contract grant number: R21-AA017410 (to A.v.d.K. and E.M.); Contract grant sponsor: NIMH Grant; Contract grant number: R21MH096559 (to B. Laughton, E. M., and A.v.d.K.); Contract grant sponsor: NRF/DST South African Research Chairs Initiative (to E. M.); Contract grant sponsor: South African Medical Research Council; Contract grant sponsor: State of Michigan [Joseph Young, Sr., Fund (to S.W.J. and J.L.J.) NR 74 TC 13 Z9 13 U1 1 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD JAN PY 2015 VL 36 IS 1 BP 170 EP 186 DI 10.1002/hbm.22620 PG 17 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AW3ML UT WOS:000346190800013 PM 25182535 ER PT J AU Kwok, VPY Wang, TF Chen, SP Yakpo, K Zhu, LL Fox, PT Tan, LH AF Kwok, Veronica P. Y. Wang, Tianfu Chen, Siping Yakpo, Kofi Zhu, Linlin Fox, Peter T. Tan, Li Hai TI Neural Signatures of Lexical Tone Reading SO HUMAN BRAIN MAPPING LA English DT Article DE functional magnetic resonance imaging; language; pitch; prosody; temporal cortex; activation likelihood estimation ID HUMAN AUDITORY-CORTEX; CROSS-LINGUISTIC PET; LANGUAGE EXPERIENCE; SPEECH-PERCEPTION; BRAIN-DAMAGE; PITCH; CHINESE; CONNECTIVITY; ACTIVATION; PATTERNS AB Research on how lexical tone is neuroanatomically represented in the human brain is central to our understanding of cortical regions subserving language. Past studies have exclusively focused on tone perception of the spoken language, and little is known as to the lexical tone processing in reading visual words and its associated brain mechanisms. In this study, we performed two experiments to identify neural substrates in Chinese tone reading. First, we used a tone judgment paradigm to investigate tone processing of visually presented Chinese characters. We found that, relative to baseline, tone perception of printed Chinese characters were mediated by strong brain activation in bilateral frontal regions, left inferior parietal lobule, left posterior middle/medial temporal gyrus, left inferior temporal region, bilateral visual systems, and cerebellum. Surprisingly, no activation was found in superior temporal regions, brain sites well known for speech tone processing. In activation likelihood estimation (ALE) meta-analysis to combine results of relevant published studies, we attempted to elucidate whether the left temporal cortex activities identified in Experiment one is consistent with those found in previous studies of auditory lexical tone perception. ALE results showed that only the left superior temporal gyrus and putamen were critical in auditory lexical tone processing. These findings suggest that activation in the superior temporal cortex associated with lexical tone perception is modality-dependent. Hum Brain Mapp, 36:304-312, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [Kwok, Veronica P. Y.; Fox, Peter T.] Univ Hong Kong, State Key Lab Brain & Cognit Sci, Hong Kong, Hong Kong, Peoples R China. [Kwok, Veronica P. Y.; Yakpo, Kofi] Univ Hong Kong, Dept Linguist, Hong Kong, Hong Kong, Peoples R China. [Wang, Tianfu; Chen, Siping; Tan, Li Hai] Shenzhen Univ, Sch Med, Dept Biomed Engn, Shenzhen 518060, Peoples R China. [Wang, Tianfu; Chen, Siping; Tan, Li Hai] Guangdong Key Lab Biomed Informat Detect & Ultras, Shenzhen 518060, Peoples R China. [Zhu, Linlin] Beijing Inst Technol, Sch Comp Sci, Beijing 100081, Peoples R China. [Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Fox, Peter T.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Tan, LH (reprint author), Shenzhen Univ, Sch Med, Dept Biomed Engn, Neuroimaging Unit, Shenzhen 518060, Peoples R China. EM lihaitan@gmail.com FU National Strategic Basic Research Program ("973" Program) of the Ministry of Science and Technology of China [2012CB720701]; National Natural Science Foundation of China [61372006] FX Contract grant sponsor: National Strategic Basic Research Program ("973" Program) of the Ministry of Science and Technology of China; Contract grant number: 2012CB720701; Contract grant sponsor: National Natural Science Foundation of China; Contract grant number: 61372006. NR 41 TC 3 Z9 4 U1 2 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD JAN PY 2015 VL 36 IS 1 BP 304 EP 312 DI 10.1002/hbm.22629 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AW3ML UT WOS:000346190800021 PM 25196948 ER PT J AU Chen, GL Dudley, J Tseng, LH Smith, K Gurda, GT Gocke, CD Eshleman, JR Lin, MT AF Chen, Guoli Dudley, Jonathan Tseng, Li-Hui Smith, Kirstin Gurda, Grzegorz T. Gocke, Christopher D. Eshleman, James R. Lin, Ming-Tseh TI Lymph node metastases of melanoma: challenges for BRAF mutation detection SO HUMAN PATHOLOGY LA English DT Article DE Melanoma; BRAF; Lymph node; Tumor cellularity; Mutant allele-specific imbalance ID PAPILLARY THYROID-CANCER; CLINICOPATHOLOGICAL FEATURES; KRAS MUTATIONS; V600 MUTATIONS; OPEN-LABEL; VEMURAFENIB; SURVIVAL; ASSAY; GENE; PERCENTAGE AB Detection of B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutations is required to predict response to BRAF or mitogen-activated protein kinase kinase 1 and 2 inhibitors in metastatic melanoma. Lymph node (LN) specimens carrying melanoma cells intermingled with abundant lymphocytes often contain low tumor cellularity. This study is aimed to examine challenges in the clinical detection of BRAF mutations in LN specimens with metastatic melanoma and to illustrate characteristic features of p.V600E and non-p.V600E mutations. In this retrospective study for quality assessment of the pyrosequencing assay, we compared characteristics of 53 LN and 135 non-LN formalin-fixed, paraffin-embedded specimens with metastatic melanoma submitted for BRAF mutation detection over a 40-month period. LN specimens showed a significantly higher incidence of p.V600E mutations than non-LN specimens (49% versus 22%, P < .01) but a significantly lower tumor cellularity, particularly in the case of subcapsular or infiltrative metastases. Mutant allele-specific imbalance of the p.V600E mutation was predominantly present in specimens with distant organ metastases (79% versus 27% in LN metastases versus 13% in primary cutaneous tumors or adjacent soft tissue, P < .001). p.V600K was detected in 23% of men older than 60 years old, compared with 6% in women older than 60 years old and 2% in both men and women younger than 60 years old (P < .001). LN specimens with low tumor cellularity due to numerous adjacent lymphocytes may pose a challenge to clinical detection of BRAF mutations of melanoma. The higher incidence of p.V600E mutations in LNs may prompt further studies to elucidate if the p.V600E mutation in primary tumors is associated with a higher risk of LN metastasis. (C) 2014 Elsevier Inc. All rights reserved. C1 [Chen, Guoli; Dudley, Jonathan; Tseng, Li-Hui; Smith, Kirstin; Gurda, Grzegorz T.; Gocke, Christopher D.; Eshleman, James R.; Lin, Ming-Tseh] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA. [Chen, Guoli] Penn State Hershey Med Ctr, Dept Pathol, Hershey, PA 17033 USA. [Dudley, Jonathan] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Tseng, Li-Hui] Natl Taiwan Univ Hosp, Dept Med Genet, Taipei 100, Taiwan. [Gocke, Christopher D.; Eshleman, James R.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21287 USA. RP Lin, MT (reprint author), Dept Pathol, Pk SB202,600 North Wolfe St, Baltimore, MD 21287 USA. EM mlin36@jhmi.edu OI TSENG, LI-HUI/0000-0002-8308-6772 NR 35 TC 6 Z9 6 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 EI 1532-8392 J9 HUM PATHOL JI Hum. Pathol. PD JAN PY 2015 VL 46 IS 1 BP 113 EP 119 DI 10.1016/j.humpath.2014.09.014 PG 7 WC Pathology SC Pathology GA AW8WL UT WOS:000346540100014 PM 25456393 ER PT J AU Zamani, P Bluemke, DA Jacobs, DR Duprez, DA Kronmal, R Lilly, SM Ferrari, VA Townsend, RR Lima, JA Budoff, M Segers, P Hannan, P Chirinos, JA AF Zamani, Payman Bluemke, David A. Jacobs, David R., Jr. Duprez, Daniel A. Kronmal, Richard Lilly, Scott M. Ferrari, Victor A. Townsend, Raymond R. Lima, Joao A. Budoff, Matthew Segers, Patrick Hannan, Peter Chirinos, Julio A. TI Resistive and Pulsatile Arterial Load as Predictors of Left Ventricular Mass and Geometry The Multi-Ethnic Study of Atherosclerosis SO HYPERTENSION LA English DT Article DE hypertrophy, left ventricular; vascular resistance; ventricular remodeling ID PRESERVED EJECTION FRACTION; PRESSURE WAVE-FORM; CARDIOVASCULAR RISK-FACTORS; SEX-DIFFERENCES; HEART-FAILURE; DIASTOLIC FUNCTION; NONINVASIVE EVALUATION; UPPER-LIMB; BODY-SIZE; REFLECTION AB Arterial load is composed of resistive and various pulsatile components, but their relative contributions to left ventricular (LV) remodeling in the general population are unknown. We studied 4145 participants enrolled in the Multi-Ethnic Study of Atherosclerosis, who underwent cardiac MRI and radial arterial tonometry. We computed systemic vascular resistance (SVR=mean arterial pressure/cardiac output) and indices of pulsatile load including total arterial compliance (TAC, approximated as stroke volume/central pulse pressure), forward wave amplitude (P-f), and reflected wave amplitude (P-b). TAC and SVR were adjusted for body surface area to allow for appropriate sex comparisons. We performed allometric adjustment of LV mass for body size and sex and computed standardized regression coefficients (beta) for each measure of arterial load. In multivariable regression models that adjusted for multiple confounders, SVR (beta=0.08; P<0.001), TAC (beta=0.44; P<0.001), P-b (beta=0.73; P<0.001), and P-f (beta=-0.23; P=0.001) were significant independent predictors of LV mass. Conversely, TAC (beta=-0.43; P<0.001), SVR (beta=0.22; P<0.001), and P-f (beta=-0.18; P=0.004) were independently associated with the LV wall/LV cavity volume ratio. Women demonstrated greater pulsatile load than men, as evidenced by a lower indexed TAC (0.89 versus 1.04 mL/mm Hg per square meter; P<0.0001), whereas men demonstrated a higher indexed SVR (34.0 versus 32.8 Wood Unitsxm2; P<0.0001). In conclusion, various components of arterial load differentially associate with LV hypertrophy and concentric remodeling. Women demonstrated greater pulsatile load than men. For both LV mass and the LV wall/LV cavity volume ratio, the loading sequence (ie, early load versus late load) is an important determinant of LV response to arterial load. C1 [Zamani, Payman; Ferrari, Victor A.; Chirinos, Julio A.] Hosp Univ Penn, Div Cardiovasc Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Zamani, Payman; Ferrari, Victor A.; Chirinos, Julio A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. [Bluemke, David A.] Johns Hopkins Univ, Sch Med, Dept Med Radiol, Baltimore, MD USA. [Jacobs, David R., Jr.; Hannan, Peter] Univ Minnesota, Sch Med, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA. [Duprez, Daniel A.] Univ Minnesota, Sch Med, Div Cardiol, Minneapolis, MN 55455 USA. [Kronmal, Richard] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. [Lilly, Scott M.] Ohio State Univ, Heart & Vasc Ctr, Div Cardiovasc Med, Columbus, OH 43210 USA. [Townsend, Raymond R.] Univ Penn, Perelman Sch Med, Div Nephrol & Hypertens, Philadelphia, PA 19104 USA. [Lima, Joao A.] Johns Hopkins Univ Hosp, Div Cardiol, Baltimore, MD 21287 USA. [Budoff, Matthew] Las Angeles Biomed Res Inst, Torrance, CA USA. [Segers, Patrick] Univ Ghent, Minds Med IT, IBiTech, B-9000 Ghent, Belgium. RP Zamani, P (reprint author), Hosp Univ Penn, Div Cardiovasc Med, 3400 Spruce St,8 Gates, Philadelphia, PA 19104 USA. EM pzamani@upenn.edu RI Lilly, Scott/K-3620-2013; OI Lilly, Scott/0000-0002-2597-6806; Bluemke, David/0000-0002-8323-8086 FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169]; National Center for Research Resources [UL1-TR-000040, UL1-RR-025005, RR-024156]; National Institutes of Aging [1R21AG043802-01, R01 HL098382]; Institute for Translational Medicine and Therapeutics of the University of Pennsylvania from the National Center for Research Resources [5UL1TR000003-09]; [5-T32-HL007843-17] FX This research was supported by contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 from the National Heart, Lung, and Blood Institute, grants UL1-TR-000040, UL1-RR-025005, and RR-024156 from National Center for Research Resources, and National Institutes of Aging grant 1R21AG043802-01 (Dr Chirinos), and R01 HL098382 (Dr Jacobs). Dr Zamani is supported, in part, by the Institute for Translational Medicine and Therapeutics of the University of Pennsylvania (grant number: 5UL1TR000003-09 from the National Center for Research Resources) and by 5-T32-HL007843-17. NR 47 TC 12 Z9 12 U1 0 U2 5 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 2015 VL 65 IS 1 BP 85 EP + DI 10.1161/HYPERTENSIONAHA.114.04333 PG 12 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AW4KA UT WOS:000346248800020 PM 25287396 ER PT J AU Bledsoe, JR Christiani, DC Kradin, RL AF Bledsoe, Jacob R. Christiani, David C. Kradin, Richard L. TI Smoking-associated fibrosis and pulmonary asbestosis SO INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE LA English DT Article DE asbestos; smoking; pulmonary fibrosis ID OF-AMERICAN-PATHOLOGISTS; RESPIRATORY BRONCHIOLITIS; DIAGNOSTIC-CRITERIA; INITIAL MANAGEMENT; DISEASES; ABNORMALITIES; ATTRIBUTION; OPACITIES; COMMITTEE; WORKERS AB The diagnosis of pulmonary asbestosis is most often established based on clinical criteria and has both clinical and legal implications. Unfortunately, one of the confounding features in the diagnosis may be a history of cigarette abuse, which can produce interstitial opacities on chest imaging as well as diffusion defects on pulmonary function testing, criteria that are used in the diagnosis of pulmonary asbestosis. The objective of the present study was to evaluate the correlation of radiographically detected pulmonary fibrosis with fibrosis established histopathologically as attributable to asbestos, in a cohort referred for diagnosis of an asbestos-related malignancy in the context of litigation. We examined the slides of 186 cases with reported asbestos exposure, referred in consultation for asbestos-related malignancy and the presence of pulmonary fibrosis. Sixty-five cases had what was judged to be adequate tissue sampling for histopathologic evaluation of asbestosis as well as an existing radiologic assessment of pulmonary fibrosis by B-reader report. Of 24 cases judged to have asbestosis radiographically, which had sufficient tissue for pathologic examination, six showed asbestosis histopathologically. The remaining 18 cases (mean smoking history of 53 pack-years) showed interstitial fibrosis that was judged to be most consistent with smoking-associated pulmonary fibrosis. We conclude that the clinical diagnosis of mild asbestosis cannot be reliably distinguished from interstitial fibrosis in heavy smokers. C1 [Bledsoe, Jacob R.; Kradin, Richard L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Christiani, David C.; Kradin, Richard L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Kradin, RL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren Bldg 253,55 Fruit St, Boston, MA 02114 USA. EM rkradin@partners.org NR 20 TC 4 Z9 4 U1 1 U2 3 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-2005 J9 INT J CHRONIC OBSTR JI Int. J. Chronic Obstr. Pulm. Dis. PY 2015 VL 10 BP 31 EP 37 DI 10.2147/COPD.S74643 PG 7 WC Respiratory System SC Respiratory System GA AW9KL UT WOS:000346575900002 PM 25565798 ER PT J AU Lin, F Roiland, R Chen, DG Qiu, C AF Lin, Feng Roiland, Rachel Chen, Ding-Geng (Din) Qiu, Christina TI Linking cognition and frailty in middle and old age: metabolic syndrome matters SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE frailty; executive function; episodic memory; metabolic syndrome ID INSULIN-RESISTANCE; ASSOCIATION; ADULTS; PHENOTYPE; QUALITY; PROGRAM; DECLINE; HEALTH AB ObjectivesThis study examined whether metabolic syndrome (MetS) would moderate the association of cognition with frailty in middle and old age. MethodsA cross-sectional design was used. Six hundred and ninety participants (age50years) from an on-going national survey were included in the study. Confirmatory factor analysis was applied to determine latent variables of executive function (EF), episodic memory (EM), and MetS based on relevant measurements. Frailty was defined using a modified form of Fried's criteria. ResultsApplying structural equation modeling, having MetS significantly increased the likelihood of being frail. Better performance on EM tasks, but not EF, was significantly associated with lower likelihood of MetS. Worse performance on EF, but not EM, significantly increased the likelihood of being frail. There was a significant interacting effect between MetS and EF, but not EM, on frailty. Further contrast analysis indicated that having MetS strengthened the negative association between EF and frailty. ConclusionMetabolic syndrome moderates the relationship between EF and frailty. A prospecitve study is needed to validate such relationships before developing interventions targeting the prevention or treatment of EF and frailty in individuals with MetS. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Lin, Feng; Chen, Ding-Geng (Din); Qiu, Christina] Univ Rochester, Sch Nursing, Rochester, NY 14642 USA. [Lin, Feng] Univ Rochester, Sch Med & Dent, Dept Psychiat, Rochester, NY 14642 USA. [Roiland, Rachel] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Chen, Ding-Geng (Din)] Univ Rochester, Sch Med & Dent, Dept Biostat & Computat Sci, Rochester, NY USA. RP Lin, F (reprint author), Univ Rochester, Sch Nursing, Rochester, NY 14642 USA. EM vankee_lin@urmc.rochester.edu FU National Institute on Aging [P01-AG020166]; University of Rochester CTSA award from the National Center for Advancing Translational Sciences of the National Institutes of Health [KL2 TR000095] FX MIDUS II was supported by from the National Institute on Aging (P01-AG020166).; The manuscript development was supported by the University of Rochester CTSA award number KL2 TR000095 from the National Center for Advancing Translational Sciences of the National Institutes of Health to F. Lin. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 32 TC 5 Z9 5 U1 2 U2 5 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 2015 VL 30 IS 1 BP 64 EP 71 DI 10.1002/gps.4115 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA AW4WM UT WOS:000346278300007 PM 24733716 ER PT J AU Holliday, EB Yang, G Jagsi, R Hoffman, KE Bennett, KE Grace, C Zietman, AL AF Holliday, Emma B. Yang, George Jagsi, Reshma Hoffman, Karen E. Bennett, Katherine Egan Grace, Calley Zietman, Anthony L. TI Fate of Manuscripts Rejected From the Red Journal SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID ACADEMY-OF-DERMATOLOGY; OPEN ACCESS; RADIATION ONCOLOGY; PUBLICATION; NEURORADIOLOGY; AUTHORSHIP; MEDICINE; OUTCOMES; FACULTY AB Purpose: To evaluate characteristics associated with higher rates of acceptance for original manuscripts submitted for publication to the International Journal of Radiation Oncology circle Biology circle Physics (IJROBP) and describe the fate of rejected manuscripts. Methods and Materials: Manuscripts submitted to the IJROBP from May 1, 2010, to August 31, 2010, and May 1, 2012, to August 31, 2012, were evaluated for author demographics and acceptance status. A PubMed search was performed for each IJROBP-rejected manuscript to ascertain whether the manuscript was ultimately published elsewhere. The Impact Factor of the accepting journal and the number of citations of the published manuscript were also collected. Results: Of the 500 included manuscripts, 172 (34.4%) were accepted and 328 (65.6%) were rejected. There was no significant difference in acceptance rates according to gender or degree of the submitting author, but there were significant differences seen based on the submitting author's country, rank, and h-index. On multivariate analysis, earlier year submitted (P<.0001) and higher author h-index (P=.006) remained significantly associated with acceptance into the IJROBP. Two hundred thirty-five IJROBP-rejected manuscripts (71.7%) were ultimately published in a PubMed-listed journal as of July 2014. There were no significant differences in any submitting author characteristics. Journals accepting IJROBP-rejected manuscripts had a lower median [interquartile range] 2013 impact factor compared with the IJROBP (2.45 [1.53-3.71] vs 4.176). The IJROBP-rejected manuscripts ultimately published elsewhere had a lower median [interquartile range] number of citations (1 [0-4] vs 6 [2-11]; P<.001), which persisted on multivariate analysis. Conclusions: The acceptance rate for manuscripts submitted to the IJROBP is approximately one-third, and approximately 70% of rejected manuscripts are ultimately published in other PubMed-listed journals, but these ultimate-destination journals usually have a lower impact factor, leading to fewer citations and overall visibility. (C) 2015 Elsevier Inc. C1 [Holliday, Emma B.; Hoffman, Karen E.] Univ Texas MD Anderson Canc Ctr, Div Radiat Oncol, Houston, TX 78240 USA. [Yang, George] Univ S Florida, Morsani Coll Med, Tampa, FL USA. [Jagsi, Reshma] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. [Bennett, Katherine Egan; Grace, Calley] Amer Soc Radiat Oncol, Fairfax, VA USA. [Zietman, Anthony L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Holliday, EB (reprint author), Univ Texas MD Anderson Canc Ctr, Div Radiat Oncol, 1515 Holcombe Blvd, Houston, TX 78240 USA. EM emmaholliday@gmail.com OI Jagsi, Reshma/0000-0001-6562-1228 NR 25 TC 1 Z9 1 U1 1 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN 1 PY 2015 VL 91 IS 1 BP 3 EP 10 DI 10.1016/j.ijrobp.2014.10.003 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AW7AA UT WOS:000346415500002 PM 25835616 ER PT J AU Tseng, YD Chen, YH Catalano, PJ Ng, A AF Tseng, Yolanda D. Chen, Yu-Hui Catalano, Paul J. Ng, Andrea TI Rates and Durability of Response to Salvage Radiation Therapy Among Patients With Refractory or Relapsed Aggressive Non-Hodgkin Lymphoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID CHEMOTHERAPY; RADIOTHERAPY AB Purpose: To evaluate the response rate (RR) and time to local recurrence (TTLR) among patients who received salvage radiation therapy for relapsed or refractory aggressive non-Hodgkin lymphoma (NHL) and investigate whether RR and TTLR differed according to disease characteristics. Methods and Materials: A retrospective review was performed for all patients who completed a course of salvage radiation therapy between January 2001 and May 2011 at Brigham and Women's Hospital/Dana-Farber Cancer Institute. Separate analyses were conducted for patients treated with palliative and curative intent. Predictors of RR for each subgroup were assessed using a generalized estimating equation model. For patients treated with curative intent, local control (LC) and progression-free survival were estimated with the Kaplan-Meier method; predictors for TTLR were evaluated using a Cox proportional hazards regression model. Results: Salvage radiation therapy was used to treat 110 patients to 121 sites (76 curative, 45 palliative). Salvage radiation therapy was given as part of consolidation in 18% of patients treated with curative intent. Median dose was 37.8 Gy, with 58% and 36% of curative and palliative patients, respectively, receiving 39.6 Gy or higher. The RR was high (86% curative, 84% palliative). With a median follow-up of 4.8 years among living patients, 5-year LC and progression-free survival for curative patients were 66% and 34%, respectively. Refractory disease (hazard ratio 3.3; P=.024) and lack of response to initial chemotherapy (hazard ratio 4.3; P=.007) but not dose (P=.93) were associated with shorter TTLR. Despite doses of 39.6 Gy or higher, 2-year LC was only 61% for definitive patients with refractory disease or disease that did not respond to initial chemotherapy. Conclusions: Relapsed or refractory aggressive NHL is responsive to salvage radiation therapy, and durable LC can be achieved in some cases. However, refractory disease is associated with a shorter TTLR, suggesting that radiation dose escalation, addition of radiosensitizers, or a combination of both may be indicated in these patients. (C) 2015 Elsevier Inc. C1 [Tseng, Yolanda D.] Univ Washington, Dept Radiat Oncol, Seattle, WA 98195 USA. [Chen, Yu-Hui; Catalano, Paul J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Catalano, Paul J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Ng, Andrea] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. RP Tseng, YD (reprint author), Univ Washington, Dept Radiat Oncol, 1959 NE Pacific St,Box 356049, Seattle, WA 98195 USA. EM ydt2@uw.edu NR 12 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN 1 PY 2015 VL 91 IS 1 BP 223 EP 231 DI 10.1016/j.ijrobp.2014.09.041 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AW7AA UT WOS:000346415500030 PM 25835625 ER PT J AU Nwachukwu, BU McCormick, F Provencher, MT Roche, M Rubash, HE AF Nwachukwu, Benedict U. McCormick, Frank Provencher, Matthew T. Roche, Martin Rubash, Harry E. TI A Comprehensive Analysis of Medicare Trends in Utilization and Hospital Economics for Total Knee and Hip Arthroplasty From 2005 to 2011 SO JOURNAL OF ARTHROPLASTY LA English DT Article DE economics; utilization; total hip arthroplasty; total knee arthroplasty; medicare; United States ID UNITED-STATES; DEMAND AB The purpose of this study was to determine annual Medicare utilization and hospital reimbursement rates for total knee arthroplasty (TKA) and total hip arthroplasty (THA). A PearlDiver review of the entire Medicare database was conducted: 2,040,667 TKAs and 855, 899 THAs performed between 2005 and 2011 were identified. There was a +0.05% and +1.3% year over year growth in the utilization in hospital reimbursement for TKA and THA respectively. There has only been a modest increase in joint arthroplasty utilization for Medicare beneficiaries. Supply side issues, insurance mix and possible prior over-projection may explain this finding. Reimbursement trends suggest that joint arthroplasty may not be a major cost driver for the healthcare system. (C) 2014 Elsevier Inc. All rights reserved. C1 [Nwachukwu, Benedict U.; Roche, Martin] Hosp Special Surg, New York, NY 10021 USA. [McCormick, Frank] Holy Cross Orthoped Inst, Ft Lauderdale, FL USA. [Provencher, Matthew T.; Rubash, Harry E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP McCormick, F (reprint author), 5597 Dixie Hwy, Ft Lauderdale, FL USA. NR 19 TC 7 Z9 7 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 EI 1532-8406 J9 J ARTHROPLASTY JI J. Arthroplast. PD JAN PY 2015 VL 30 IS 1 BP 15 EP 18 DI 10.1016/j.arth.2014.08.025 PG 4 WC Orthopedics SC Orthopedics GA AW6OE UT WOS:000346387900004 PM 25267535 ER PT J AU Rychert, J Creely, D Mayo-Smith, LM Calderwood, SB Ivers, LC Ryan, ET Boncy, J Qadri, F Ahmed, D Ferraro, MJ Harris, JB AF Rychert, Jenna Creely, David Mayo-Smith, Leslie M. Calderwood, Stephen B. Ivers, Louise C. Ryan, Edward T. Boncy, Jacques Qadri, Firdausi Ahmed, Dilruba Ferraro, Mary Jane Harris, Jason B. TI Evaluation of Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry for Identification of Vibrio cholerae SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID FAMILY VIBRIONACEAE; MEMBERS AB We evaluated the use of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MS) for the identification of Vibrio cholerae. MS identified all 42 isolates of V. cholerae O1 and O139 and 7 of 9 non-O1/O139 isolates. MS correctly discriminated between all Aeromonas and V. cholerae isolates. Overall, MS performed as well as or better than biochemical methods. C1 [Rychert, Jenna; Ferraro, Mary Jane] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Rychert, Jenna; Calderwood, Stephen B.; Ryan, Edward T.; Ferraro, Mary Jane; Harris, Jason B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Rychert, Jenna; Mayo-Smith, Leslie M.; Calderwood, Stephen B.; Ryan, Edward T.; Harris, Jason B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Harris, Jason B.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Creely, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Creely, David] Harvard Univ, Sch Med, Boston, MA USA. [Creely, David] bioMerieux, Hazelwood, MO USA. [Ivers, Louise C.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Ivers, Louise C.] Partners Hlth, Boston, MA USA. [Boncy, Jacques] Natl Publ Hlth Lab, Port Au Prince, Haiti. [Qadri, Firdausi; Ahmed, Dilruba] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. RP Rychert, J (reprint author), ARUP Labs, Salt Lake City, UT 84108 USA. EM jbharris@partners.org FU National Institute of Allergy and Infectious Diseases [AI099243, AI103055, AI077883, AI058935, AI106878] FX This work was supported by grants from the National Institute of Allergy and Infectious Diseases (AI099243 to J.B.H. and L.C.I.; AI103055 to J.B.H.; and AI077883, AI058935, and AI106878 to E.T.R.). NR 9 TC 3 Z9 5 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 EI 1098-660X J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JAN PY 2015 VL 53 IS 1 BP 329 EP 331 DI 10.1128/JCM.02666-14 PG 3 WC Microbiology SC Microbiology GA AW8HM UT WOS:000346502200053 PM 25392355 ER PT J AU Li, XD Pezeshkpour, G Phan, RT AF Li, Xiaodong Pezeshkpour, G. Phan, Ryan T. TI KRAS mutation status impacts diagnosis and treatment decision in a patient with two colon tumours: a case report SO JOURNAL OF CLINICAL PATHOLOGY LA English DT Article ID METASTATIC COLORECTAL-CANCER; RAS MUTATIONS; HETEROGENEITY AB KRAS mutation status predicts response to anti-EGFR therapy in colorectal cancer patients. Here we report an interesting case of discordant KRAS mutation status in a patient with two separate tumour foci. Tumour A in sigmoid colon invaded through muscularis propria into the subserosal fat with metastatic disease in regional lymph nodes (pT3N2b). Tumour B in ascending colon had a relatively lower stage and no metastasis (pT2N0). Both tumours showed similar morphology, immunohistochemical staining and microsatellite instability pattern. KRAS mutation, however, was detected only in tumour A. These findings indicate distinct clonal nature of these two tumours. The discordance of KRAS mutation status also suggests that a combination of anti-epidermal growth factor receptor and chemotherapy is likely the best treatment option for this patient. This case exemplifies a notion that comprehensive pathological work-up comprising molecular testing is critical to guide the diagnosis and treatment decisions for colorectal cancer patients with multiple tumours. C1 [Li, Xiaodong; Pezeshkpour, G.; Phan, Ryan T.] Univ So Calif, Keck Sch Med, USC LAC Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90033 USA. [Pezeshkpour, G.; Phan, Ryan T.] VA Greater Los Angles Healthcare Syst, Dept Pathol & Lab Med, Los Angeles, CA 90073 USA. RP Phan, RT (reprint author), VA Greater Los Angles Healthcare Syst, Dept Pathol & Lab Med, 11301 Wilshire Blvd,Bldg 500,Room 1255, Los Angeles, CA 90073 USA. EM Ryan.Phan@va.gov NR 15 TC 3 Z9 3 U1 0 U2 7 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0021-9746 EI 1472-4146 J9 J CLIN PATHOL JI J. Clin. Pathol. PD JAN PY 2015 VL 68 IS 1 BP 83 EP 85 DI 10.1136/jclinpath-2014-202591 PG 3 WC Pathology SC Pathology GA AW5ZU UT WOS:000346350200016 PM 25313410 ER PT J AU Valentine, SE Bankoff, SM Poulin, RM Reidler, EB Pantalone, DW AF Valentine, Sarah E. Bankoff, Sarah M. Poulin, Renee M. Reidler, Esther B. Pantalone, David W. TI The Use of Dialectical Behavior Therapy Skills Training as Stand-Alone Treatment: A Systematic Review of the Treatment Outcome Literature SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE skills training; dialectical behavior therapy; DBT; review ID BORDERLINE PERSONALITY-DISORDER; BINGE-EATING DISORDER; RANDOMIZED CONTROLLED-TRIAL; CLINICAL-TRIAL; WOMEN; DBT; DEPRESSION; CRITERIA; EXPERTS AB ObjectiveDialectical behavior therapy (DBT) skills training is currently being administered as stand-alone treatment across a variety of clinical settings, serving diverse client populations. However, there is little empirical support for this use. MethodIn this systematic review, we identified 17 trials employing a treatment that included DBT skills training in the absence of the other DBT modalities. ResultsWhile the literature reviewed provides preliminary evidence of the utility of DBT skills training to address a range of mental health and behavioral problems, methodological limitations of published studies preclude us from drawing strong conclusions about the efficacy of skills training as a stand-alone treatment. ConclusionWe present an overview of the implementation of DBT skills training across clinical settings and populations. We found preliminary evidence supporting the use of DBT skills training as a method of addressing a range of behaviors. We provide recommendations for future research. C1 [Valentine, Sarah E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Chelsea, MA 02150 USA. [Valentine, Sarah E.; Poulin, Renee M.; Reidler, Esther B.] Suffolk Univ, Boston, MA 02108 USA. [Bankoff, Sarah M.] VA Boston Healthcare Syst, Boston, MA USA. [Pantalone, David W.] Univ Massachusetts Boston, Boston, MA USA. [Pantalone, David W.] Fenway Hlth, Fenway Inst, Boston, MA USA. RP Valentine, SE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Community Psychiat PRIDE, 70 Everett Ave,Suite 516, Chelsea, MA 02150 USA. EM sevalen-tine@mgh.harvard.edu NR 44 TC 10 Z9 10 U1 7 U2 59 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9762 EI 1097-4679 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD JAN PY 2015 VL 71 IS 1 BP 1 EP 20 DI 10.1002/jclp.22114 PG 20 WC Psychology, Clinical SC Psychology GA AW5YM UT WOS:000346346800001 PM 25042066 ER PT J AU Van Dyke, TE Hasturk, H Kantarci, A Freire, MO Nguyen, D Dalli, J Serhan, CN AF Van Dyke, T. E. Hasturk, H. Kantarci, A. Freire, M. O. Nguyen, D. Dalli, J. Serhan, C. N. TI Proresolving Nanomedicines Activate Bone Regeneration in Periodontitis SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE periodontal disease; cardiovascular disease; bacteremia; resolution of inflammation; lipoxins; resolvins ID LIPID MEDIATORS; RESOLVIN E1; INFLAMMATION; MICROPARTICLES; RESOLUTION; DIFFERENTIATION; LEUKOTRIENES; RESORPTION AB Therapies to reverse tissue damage from osteolytic inflammatory diseases are limited by the inability of current tissue-engineering procedures to restore lost hard and soft tissues. There is a critical need for new therapeutics in regeneration. In addition to scaffolds, cells, and soluble mediators necessary for tissue engineering, control of endogenous inflammation is an absolute requirement for success. Although significant progress has been made in understanding natural resolution of inflammation pathways to limit uncontrolled inflammation in disease, harnessing the biomimetic properties of proresolving lipid mediators has not been demonstrated. Here, we report the use of nano-proresolving medicines (NPRM) containing a novel lipoxin analog (benzo-lipoxin A(4), bLXA(4)) to promote regeneration of hard and soft tissues irreversibly lost to periodontitis in the Hanford miniature pig. In this proof-of-principle experiment, NPRM-bLXA(4) dramatically reduced inflammatory cell infiltrate into chronic periodontal disease sites treated surgically and dramatically increased new bone formation and regeneration of the periodontal organ. These findings indicate that NPRM-bLXA(4) is a mimetic of endogenous resolving mechanisms with potent bioactions that offers a new therapeutic tissue-engineering approach for the treatment of chronic osteolytic inflammatory diseases. C1 [Van Dyke, T. E.; Hasturk, H.; Kantarci, A.; Freire, M. O.; Nguyen, D.] Forsyth Inst, Dept Appl Oral Sci, Ctr Periodontol, Cambridge, MA USA. [Dalli, J.; Serhan, C. N.] Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Dalli, J.; Serhan, C. N.] Harvard Univ, Sch Med, Boston, MA USA. RP Van Dyke, TE (reprint author), Ctr Periodontol, Dept Appl Oral Sci, 245 First St, Cambridge, MA 02142 USA. EM tvandyke@forsyth.org OI Freire, Marcelo/0000-0003-4906-7698 FU USPHS National Institute of Dental and Craniofacial Research (NIDCR) [DE19938, DE15566, DE18917] FX The authors of this study thank the veterinary and technical personnel of the Forsyth Institute Animal Center and Pine Acre Research Farm for assistance during animal handling and experimental procedures and the Organic Synthesis Core of P50-DE016191 (to C.N.S.) for preparing NPRM and bLXA4. This study was partly supported by the USPHS National Institute of Dental and Craniofacial Research (NIDCR) grants (DE19938 and DE15566 to T.E. Van Dyke; DE18917 to H. Hasturk). The Forsyth Institute has filed patent applications. The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. NR 35 TC 13 Z9 13 U1 1 U2 13 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 EI 1544-0591 J9 J DENT RES JI J. Dent. Res. PD JAN PY 2015 VL 94 IS 1 BP 148 EP 156 DI 10.1177/0022034514557331 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AW8IW UT WOS:000346506200019 PM 25389003 ER PT J AU Simon, TG King, LY Zheng, H Chung, RT AF Simon, Tracey G. King, Lindsay Y. Zheng, Hui Chung, Raymond T. TI Statin use is associated with a reduced risk of fibrosis progression in chronic hepatitis C SO JOURNAL OF HEPATOLOGY LA English DT Article DE Cirrhosis; Hepatitis C virus; Lipid lowering agent ID LOVASTATIN-INDUCED APOPTOSIS; HEPATOCELLULAR-CARCINOMA; LIVER FIBROSIS; VIRUS-INFECTION; UNITED-STATES; CANCER; FLUVASTATIN; THERAPY; CELLS; PEGINTERFERON AB Background & Aims: Therapies that slow fibrosis progression in chronic liver disease are needed. Animal models have demonstrated that statins prevent the progression of hepatic fibrosis, but human data is lacking so far. We evaluated the association between statins and fibrosis progression in the HALT-C trial cohort. Methods: Subjects with chronic hepatitis C (CHC) and advanced hepatic fibrosis underwent serial liver biopsies over 3.5 years. The primary outcome was a >= 2-point increase in the Ishak fibrosis score on at least one of two serial biopsies. We used complementary log-log regression analysis to assess the association between statins and fibrosis progression among subjects without baseline cirrhosis. Results: Fibrosis progression occurred in 3/29 (10%) statin users and 145/514 (29%) non-users. The unadjusted hazard ratio (HR) for fibrosis progression among statin users compared to non-users was 0.32 (95% CI 0.10-0.99). This association remained significant after adjusting for established predictors of histological outcome, including body mass index, platelets and hepatic steatosis (adjusted HR 0.31; 95% CI 0.10-0.97). The mean change in Ishak fibrosis score over the 3.5 year study period was 0.34 (SE 0.18) for statin users compared to +0.42 (SE 0.07) for non-users (p = 0.006, after adjustment for baseline fibrosis score). Conclusions: Statin use is associated with a reduced risk of fibrosis progression in advanced CHC. Our findings suggest a potential role for statins in preventing liver disease progression. (C) 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 [Simon, Tracey G.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [King, Lindsay Y.; Chung, Raymond T.] Massachusetts Gen Hosp, Dept Med, Gastrointestinal Div, Ctr Liver, Boston, MA 02114 USA. [Zheng, Hui] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Simon, Tracey G.; King, Lindsay Y.; Zheng, Hui; Chung, Raymond T.] Harvard Univ, Sch Med, Boston, MA USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, 55 Fruit St,Warren 1007, Boston, MA 02114 USA. EM rtchung@partners.org FU [K24 DK078772]; [T32DK007191] FX This study was funded by grant K24 DK078772 to R.T. Chung and grant T32DK007191 to L.Y. King. NR 50 TC 23 Z9 25 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD JAN PY 2015 VL 62 IS 1 BP 18 EP 23 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AW6BM UT WOS:000346354500007 PM 25135867 ER PT J AU Aguilar, DD Kim, C Sweigard, H Connor, K AF Aguilar, Diaz D. Kim, C. Sweigard, H. Connor, K. TI CHARACTERIZING THE ROLE OF THE ALTERNATIVE COMPLEMENT PATHWAY IN VASCULAR REGRESSION IN A MOUSE MODEL OF RETINOPATHY SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 [Aguilar, Diaz D.] Univ Calif Los Angeles, Los Angeles, CA USA. [Kim, C.; Sweigard, H.; Connor, K.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Kim, C.; Sweigard, H.; Connor, K.] Harvard Univ, Sch Med, Boston, MA 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 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2015 VL 63 IS 1 MA 27 BP 94 EP 94 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AW9TQ UT WOS:000346600700043 ER PT J AU Noble, P Chan, G Young, M Weisbart, R Hansen, JE AF Noble, P. Chan, G. Young, M. Weisbart, R. Hansen, J. E. TI AN OPTIMIZED LUPUS AUTOANTIBODY FRAGMENT FOR TARGETED THERAPY OF DNA REPAIR-DEFICIENT MALIGNANCIES SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 [Noble, P.; Young, M.; Hansen, J. E.] Yale Univ, Sch Med, New Haven, CT USA. [Chan, G.; Weisbart, R.] Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda, CA 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 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2015 VL 63 IS 1 MA 101 BP 117 EP 117 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AW9TQ UT WOS:000346600700117 ER PT J AU Boyd, M Bream, HJ Banks, W AF Boyd, M. Bream, H. J. Banks, W. TI BLOOD BRAIN BARRIER DISRUPTION AFTER MILD TRAUMATIC BRAIN INJURY IN A CLOSED SKULL MODEL SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 [Boyd, M.; Bream, H. J.; Banks, W.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Boyd, M.; Bream, H. J.; Banks, W.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2015 VL 63 IS 1 MA 121 BP 122 EP 123 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AW9TQ UT WOS:000346600700137 ER PT J AU Bream, HJ Boyd, M Banks, W AF Bream, H. J. Boyd, M. Banks, W. TI DEVELOPMENT OF A CLOSED SKULL MODEL FOR MILD REPETITIVE TRAUMATIC BRAIN INJURY SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 [Bream, H. J.; Boyd, M.; Banks, W.] Univ Washington, Seattle, WA 98195 USA. [Bream, H. J.; Boyd, M.; Banks, W.] VA Puget Sound Hlth Care Syst, Seattle, WA 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 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2015 VL 63 IS 1 MA 122 BP 123 EP 123 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AW9TQ UT WOS:000346600700138 ER PT J AU Szkudlinska, MA von Frankenberg, AD Utzschneider, K AF Szkudlinska, M. A. von Frankenberg, A. D. Utzschneider, K. TI THE ANTIOXIDANT N-ACETYLCYSTEINE DOES NOT IMPROVE GLUCOSE TOLERANCE OR beta-CELL FUNCTION IN TYPE 2 DIABETES SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 [Szkudlinska, M. A.; von Frankenberg, A. D.; Utzschneider, K.] Univ Washington, Seattle, WA 98195 USA. [Utzschneider, K.] VA Puget Sound Hlth Care Syst, Seattle, WA 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 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2015 VL 63 IS 1 MA 188 BP 142 EP 142 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AW9TQ UT WOS:000346600700201 ER PT J AU Zhang, J Lin, A Jimenez, E Paholpak, P Teng, E Mendez, M AF Zhang, J. Lin, A. Jimenez, E. Paholpak, P. Teng, E. Mendez, M. TI PREVALENCE OF TRAUMATIC BRAIN INJURY IN EARLY VERSUS LATE-ONSET ALZHEIMER'S DISEASE SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 [Zhang, J.; Jimenez, E.; Paholpak, P.; Teng, E.; Mendez, M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Lin, A.; Jimenez, E.; Paholpak, P.; Teng, E.; Mendez, M.] VA Greater Healthcare Syst, Neurobehav Unit, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2015 VL 63 IS 1 MA 312 BP 180 EP 180 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AW9TQ UT WOS:000346600700325 ER PT J AU Ziemke, MK Malkoski, S AF Ziemke, M. K. Malkoski, S. TI FEASABLITY OF A RETROSPECTIVE ANALYSIS DETERMINING IF REDUCED SMAD4 EXPRESSION PREDICTS RESPONSIVENESS TO DNA TOPOISMOERASE INHIBITORS IN LUNG CANCER SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 [Ziemke, M. K.; Malkoski, S.] Univ Colorado, Sch Med, Aurora, CO USA. [Ziemke, M. K.; Malkoski, S.] Denver Vet Affairs Med Ctr, Denver, CO 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 1081-5589 EI 1708-8267 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2015 VL 63 IS 1 MA 388 BP 202 EP 202 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AW9TQ UT WOS:000346600700397 ER PT J AU Zhou, YX Yu, F Duong, TQ AF Zhou, Yongxia Yu, Fang Duong, Timothy Q. CA Alzheimer's Dis Neuroimaging Initi TI White Matter Lesion Load Is Associated With Resting State Functional MRI Activity and Amyloid PET but not FDG in Mild Cognitive Impairment and Early Alzheimer's Disease Patients SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE white matter lesion; amyloid; resting state-fMRI; Alzheimer disease; fractional amplitude at low frequency fluctuation; default mode network ID BRAIN; INDIVIDUALS; MULTICENTER; DEPOSITION; DECLINE; PATTERN; MEMORY AB PurposeTo quantify and investigate the interactions between multimodal MRI/positron emission tomography (PET) imaging metrics in elderly patients with early Alzheimer's disease (AD), mild cognitive impairment (MCI) and healthy controls. Materials and MethodsThirteen early AD, 17 MCI patients, and 14 age-matched healthy aging controls from the Alzheimer's Disease Neuroimaging Initiative database were selected based on availability of data. Default mode network (DMN) functional connectivity and fractional amplitude of low frequency fluctuation (fALFF) were obtained for resting state functional MRI (RS-fMRI). White matter lesion load (WMLL) was quantified from MRI T2-weighted FLAIR images. Amyloid deposition with PET [F-18]-Florbetapir tracer and metabolism of glucose by means of [F-18]-fluoro-2-deoxyglucose (FDG) images were quantified using ratio of standard uptake values (rSUV). ResultsWhole-brain WMLL and amyloid deposition were significantly higher (P<0.005) in MCI and AD patients compared with controls. RS-fMRI results showed significantly reduced (corrected P<0.05) DMN connectivity and altered fALFF activity in both MCI and AD groups. FDG uptake results showed hypometabolism in AD and MCI patients compared with controls. Correlations (P<0.05) were found between WMLL and amyloid load, FDG uptake and amyloid load, as well as between amyloid load (rSUV) and fALFF. ConclusionOur quantitative results of four MRI and PET imaging metrics (fALFF/DMN, WMLL, amyloid, and FDG rSUV values) agree with published values. Significant correlations between MRI metrics, including WMLL/functional activity and PET amyloid load suggest the potential of MRI and PET-based biomarkers for early detection of AD.J. Magn. Reson. Imaging 2013. (c) 2013 Wiley Periodicals, Inc. J. Magn. Reson. Imaging 2015;41:102-109. (c) 2013 Wiley Periodicals, Inc. C1 [Zhou, Yongxia] NYU, Sch Med, Radiol Ctr Biomed Imaging, New York, NY 10016 USA. [Zhou, Yongxia] Univ Penn, Philadelphia, PA 19104 USA. [Yu, Fang; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Ophthalmol, San Antonio, TX 78229 USA. [Yu, Fang; Duong, Timothy Q.] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. RP Zhou, YX (reprint author), NYU, Sch Med, Dept Radiol, Ctr Biomed Imaging, 660 First Ave,4th Floor, New York, NY 10016 USA. EM yongxia.zhou@yahoo.com OI Zhou, Yongxia (Sharon)/0000-0002-4931-2318 FU National Institutes of Health [U01 AG024904, P30 AG010129, K01 AG030514] FX Contract grant sponsor: National Institutes of Health; Contract grant numbers: U01 AG024904, P30 AG010129, K01 AG030514. NR 39 TC 10 Z9 11 U1 2 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-1807 EI 1522-2586 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD JAN PY 2015 VL 41 IS 1 BP 102 EP 109 DI 10.1002/jmri.24550 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AW7EP UT WOS:000346427800011 PM 24382798 ER PT J AU Nogueira, RG Gupta, R Jovin, TG Levy, EI Liebeskind, DS Zaidat, OO Rai, A Hirsch, JA Hsu, DP Rymer, MM Tayal, AH Lin, R Natarajan, SK Nanda, A Tian, M Hao, Q Kalia, JS Chen, M Abou-Chebl, A Nguyen, TN Yoo, AJ AF Nogueira, Raul G. Gupta, Rishi Jovin, Tudor G. Levy, Elad I. Liebeskind, David S. Zaidat, Osama O. Rai, Ansaar Hirsch, Joshua A. Hsu, Daniel P. Rymer, Marilyn M. Tayal, Ashis H. Lin, Ridwan Natarajan, Sabareesh K. Nanda, Ashish Tian, Melissa Hao, Qing Kalia, Junaid S. Chen, Michael Abou-Chebl, Alex Nguyen, Thanh N. Yoo, Albert J. TI Predictors and clinical relevance of hemorrhagic transformation after endovascular therapy for anterior circulation large vessel occlusion strokes: a multicenter retrospective analysis of 1122 patients SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article ID ACUTE ISCHEMIC-STROKE; SYMPTOMATIC INTRACEREBRAL HEMORRHAGE; TISSUE-PLASMINOGEN ACTIVATOR; INTRACRANIAL HEMORRHAGE; THROMBOLYSIS; ALTEPLASE; DEFINITIONS; REPERFUSION; INFARCTION; TRIAL AB Background and purpose Endovascular techniques are frequently employed to treat large artery occlusion in acute ischemic stroke (AIS). We sought to determine the predictors and clinical impact of intracranial hemorrhage (ICH) after endovascular therapy. Methods Retrospective analysis of consecutive patients presenting to 13 high volume stroke centers with AIS due to proximal occlusion in the anterior circulation who underwent endovascular treatment within 8 h from symptom onset. Logistic regression was performed to determine the variables associated with ICH, hemorrhagic infarction (HI), and parenchymal hematomas (PHs), as well as 90 day poor outcome (modified Rankin Scale score >= 3) and mortality. Results There were a total of 363 ICHs (overall rate 32.3%; HI=267, 24%; PH=96, 8.5%) among the 1122 study patients (mean age 67 +/- 15 years; median National Institutes of Health Stroke Scale score 17 (IQR 13-20)). Independent predictors for HI included diabetes mellitus (OR 2.27, 95% CI (1.58 to 3.26), p<0.0001), preprocedure IV tissue plasminogen activator (tPA) (1.43 (1.03 to 2.08), p<0.037), Merci thrombectomy (1.47 (1.02 to 2.12), p<0.032), and longer time to puncture (1.001 (1.00 to 1.002), p<0.026). Patients with atrial fibrillation (1.61 (1.01 to 2.55), p<0.045) had a higher risk of PH while the use of IA tPA (0.57 (0.35 to 0.90), p<0.008) was associated with lower chances of PH. Both the presence of HI (2.23 (1.53 to 3.25), p<0.0001) and PH (6.24 (3.06 to 12.75), p<0.0001) were associated with poor functional outcomes; however, only PH was associated with higher mortality (3.53 (2.19 to 5.68), p<0.0001). Conclusions Greater understanding about the predictors and consequences of ICH post endovascular stroke therapy is essential to improve risk assessment, patient selection/clinical outcomes, and early prognostication. Our data suggest that patients with atrial fibrillation are particularly prone to severe ICH and question the 'benign' nature of HI suggested by earlier studies. C1 [Nogueira, Raul G.; Gupta, Rishi] Emory Univ, Sch Med, Atlanta, GA 30303 USA. [Jovin, Tudor G.; Lin, Ridwan] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Levy, Elad I.; Natarajan, Sabareesh K.; Nanda, Ashish] SUNY Buffalo, Buffalo, NY 14260 USA. [Liebeskind, David S.; Hao, Qing] Univ Calif Los Angeles, Los Angeles, CA USA. [Zaidat, Osama O.; Kalia, Junaid S.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Rai, Ansaar] W Virginia Univ, Morgantown, VA USA. [Hirsch, Joshua A.; Yoo, Albert J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hsu, Daniel P.] Univ Hosp Cleveland, Cleveland, OH 44106 USA. [Rymer, Marilyn M.] St Lukes Stroke Inst, Kansas City, KS USA. [Tayal, Ashis H.; Tian, Melissa] Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. [Chen, Michael] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Abou-Chebl, Alex] Univ Louisville, Med Ctr, Louisville, KY 40292 USA. [Nguyen, Thanh N.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Gupta, R (reprint author), Emory Univ, Sch Med, 49 Jesse Hill Dr SE,Room 393, Atlanta, GA 30303 USA. EM rishi.gupta@emory.edu FU Penumbra Corp.; Boston Scientific Corp; Micrus Endovascular; Abbott Vascular; EV3; National Institutes of Health FX AJY has research support from Penumbra Corp. TGJ is on the consultant/scientific advisory boards for CoAxia Medical and Stryker Neurovascular/Concentric Medical and is a consultant for Covidien/EV3. EIL has received a research grant from Boston Scientific Corp; research support from Micrus Endovascular, Abbott Vascular, and EV3; has received honoraria from Intratech Medical Ltd; has an ownership interest in Mynx/Access Closure and TheraSyn Sensors, Inc; and is on the consultant/advisory boards for Cordis Neurovascular and Micrus Endovascular. MMR is a speaker for Stryker Neurovascular/Concentric Medical and a consultant for Genentech. AHT is a speaker for Genentech and Boehringer Ingelheim. DSL and RGN are consultants to, and on the advisory boards for, Stryker Neurovascular/Concentric Medical, Covidien/EV3, and CoAxia. OZ is on the consultant/scientific advisory board for Stryker Neurovascular. MC is a speaker for Stryker Neurovascular/Concentric Medical. RG is on the consultant/scientific advisory boards for Stryker Neurovascular/Concentric Medical and CoAxia. DSL has received significant research support from the National Institutes of Health. NR 25 TC 8 Z9 8 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 EI 1759-8486 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD JAN PY 2015 VL 7 IS 1 BP 16 EP 21 DI 10.1136/neurintsurg-2013-010743 PG 6 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA AW4HU UT WOS:000346242600008 PM 24401478 ER PT J AU Adams, JM Hill, KS AF Adams, Jeffrey M. Hill, Karen S. TI The Influence of Administrative Leadership An Interview With Dr Karen S. Hill SO JOURNAL OF NURSING ADMINISTRATION LA English DT Editorial Material C1 [Adams, Jeffrey M.] Ctr Innovat Care Delivery, Boston, MA USA. [Adams, Jeffrey M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Adams, Jeffrey M.] Robert Wood Johnson Fdn, Princeton, NJ 08540 USA. [Hill, Karen S.] Baptist Hlth, Lexington, KY USA. RP Adams, JM (reprint author), Massachusetts Gen Hosp, 275 Cambridge St,Profess Off Bldg 432, Boston, MA 02114 USA. EM jeff.adams@mgh.harvard.edu NR 2 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 EI 1539-0721 J9 J NURS ADMIN JI J. Nurs. Adm. PD JAN PY 2015 VL 45 IS 1 BP 4 EP 6 DI 10.1097/NNA.0000000000000148 PG 3 WC Nursing SC Nursing GA AX0HR UT WOS:000346634100002 ER PT J AU Obeng, EA Harney, KM Moniz, T Arnold, A Neufeld, EJ Trenor, CC AF Obeng, Esther A. Harney, Kathy M. Moniz, Thomas Arnold, Alana Neufeld, Ellis J. Trenor, Cameron C., III TI Pediatric Heparin-Induced Thrombocytopenia: Prevalence, Thrombotic Risk, and Application of the 4Ts Scoring System SO JOURNAL OF PEDIATRICS LA English DT Article ID PARTICLE GEL IMMUNOASSAY; OPTICAL-DENSITY VALUES; OF-THE-LITERATURE; CLINICAL-FEATURES; DANAPAROID SODIUM; DIAGNOSIS; ANTIBODIES; MANAGEMENT; PROBABILITY; CHILDREN AB Objective To characterize heparin-induced thrombocytopenia (HIT) at a single pediatric center including the prevalence and the accuracy of the 4Ts scoring system as a predictor of HIT. Study design In this retrospective cohort study, we identified 155 consecutive patients <21 years old with sufficient data for 4Ts scoring. The 4Ts scoring system is a validated pretest tool in adults that predicts the likelihood of HIT using clinical features. Hospital-wide exposure to unfractionated and low molecular weight heparin was determined by querying the hospital pharmacy database. Results The majority of patients with suspected HIT (61.2%) were on surgical services. Prediction of HIT risk using initial 4Ts scoring found 3 (2%) had high risk 4Ts scores, 114 (73%) had intermediate risk 4Ts scores, and the remaining 38 (25%) had low risk 4Ts scores. HIT was confirmed in 0/38 patients with low risk 4Ts scores, 2/114 patients with intermediate-risk 4Ts scores, and all 3 patients with high-risk 4Ts scores presented with HIT with thrombosis. Of 12 positive HIT screening tests, results were falsely positive in 66.6% of patients with intermediate risk 4Ts scores and 100% of patients with low risk 4Ts scores. The prevalence of HIT was 0.058% and HIT with thrombosis was 0.046% in pediatric patients on unfractionated heparin. Conclusions The prevalence of HIT appears significantly lower in pediatric patients compared with adults. Application of the 4Ts system as a pretest tool may reduce laboratory evaluation for HIT in heparin-exposed children with low risk 4Ts scores, decreasing unnecessary further testing, intervention, and cost. C1 [Obeng, Esther A.; Harney, Kathy M.; Neufeld, Ellis J.; Trenor, Cameron C., III] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Moniz, Thomas; Arnold, Alana] Boston Childrens Hosp, Dept Pharm, Boston, MA 02115 USA. [Obeng, Esther A.; Neufeld, Ellis J.; Trenor, Cameron C., III] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Obeng, Esther A.; Neufeld, Ellis J.; Trenor, Cameron C., III] Harvard Univ, Sch Med, Boston, MA USA. RP Trenor, CC (reprint author), Boston Childrens Hosp, Div Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. EM cameron.trenor@childrens.harvard.edu FU National Heart, Lung, and Blood Institute [HL089509, HL00418410, HL007574] FX Supported by the National Heart, Lung, and Blood Institute (HL089509 [to C.T.], HL00418410 [to E.N.], and HL007574 [to E.O.]). The authors declare no conflicts of interest. NR 38 TC 8 Z9 9 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JAN PY 2015 VL 166 IS 1 BP 144 EP + DI 10.1016/j.jpeds.2014.09.017 PG 8 WC Pediatrics SC Pediatrics GA AW9NI UT WOS:000346584000030 PM 25444534 ER PT J AU Tang, GL Weitz, K AF Tang, Gale L. Weitz, Kevin TI Impaired arteriogenesis in syndecan-1(-/-) mice SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Arteriogenesis; Syndecan-1; Mouse hindlimb ischemia; Angiogenesis ID FIBROBLAST-GROWTH-FACTOR; ANGIOGENESIS; ISCHEMIA; HINDLIMB; INHIBITOR; MODEL; MACROPHAGES; EXPRESSION; MONOCYTES; SYNSTATIN AB Background: Collateral artery development (arteriogenesis) is an important compensatory response to arterial occlusion caused by atherosclerosis. The heparan sulfate proteoglycan syndecan-1 (sdc1) has previously been shown to affect the response to arterial injury but has yet been studied in arteriogenesis. We tested the hypothesis that sdc1 knockout (sdc1(-/-)) mice would revascularize more poorly than wild type (wt) mice, and then used bone marrow transplantation experiments to determine whether sdc1' s effect on arteriogenesis was due to its presence in the local tissue environment or in bone marrow derived cells. Materials and methods: Hindlimb ischemia was induced by femoral artery ligation in wt and sdc1(-/-) female mice as well as in wt and sdc1(-/-) female mice transplanted with wt bone marrow or in wt mice transplanted with sdc1(-/-) bone marrow. Blood flow recovery was assessed by laser Doppler perfusion imaging. Arteriogenesis was assessed by measuring the diameter of the dominant collateral pathway after pressure perfusion fixation and intra-aortic contrast injection at 28 d. Immunohistochemistry was used to assess angiogenesis and peri-collateral macrophage infiltration at 7 d, postoperatively. Results: Sdc1(-/-) mice had impaired blood flow recovery in response to hindlimb ischemia. This impaired recovery was not secondary to a defect in capillary angiogenesis nor was it due to decreased peri-collateral macrophage infiltration. Wt bone marrow did not rescue the impaired recovery of sdc1(-/-) mice. Conclusions: Sdc1 affects arteriogenesis in response to hindlimb ischemia and is required in the local tissue environment for normal arteriogenesis. Published by Elsevier Inc. C1 [Tang, Gale L.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Tang, Gale L.; Weitz, Kevin] Univ Washington, Dept Surg, Div Vasc Surg, Seattle, WA 98108 USA. RP Tang, GL (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Surg Serv 112,1660 South Columbian Way, Seattle, WA 98108 USA. EM gtang@uw.edu NR 28 TC 1 Z9 1 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 EI 1095-8673 J9 J SURG RES JI J. Surg. Res. PD JAN PY 2015 VL 193 IS 1 BP 22 EP 27 DI 10.1016/j.jss.2014.08.002 PG 6 WC Surgery SC Surgery GA AW4HH UT WOS:000346241300004 PM 25194470 ER PT J AU Dowling, MB Smith, W Balogh, P Duggan, MJ MacIntire, IC Harris, E Mesar, T Raghavan, SR King, DR AF Dowling, Matthew B. Smith, William Balogh, Peter Duggan, Michael J. MacIntire, Ian C. Harris, Erica Mesar, Tomaz Raghavan, Srinivasa R. King, David R. TI Hydrophobically-modified chitosan foam: description and hemostatic efficacy SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Chitosan; Hemorrhage; Spray; Bleeding; Rat; Liver ID OPERATION-IRAQI-FREEDOM; FIBRIN SEALANT FOAM; HEMORRHAGE CONTROL; ENDURING-FREEDOM; GROIN INJURY; LETHAL MODEL; BLOOD-LOSS; SWINE; SURVIVAL; EPIDEMIOLOGY AB Background: Trauma represents a significant public health burden, and hemorrhage alone is responsible for 40% of deaths within the first 24 h after injury. Noncompressible hemorrhage accounts for the majority of hemorrhage-related deaths. Thus, materials which can arrest bleeding rapidly are necessary for improved clinical outcomes. This preliminary study evaluated several self-expanding hydrophobically modified chitosan (HM-CS) foams to determine their efficacy on a noncompressible severe liver injury under resuscitation. Methods: Six HM-CS foam formulations (HM-CS1, HM-CS2, HM-CS3, HM-CS4, HM-CS5, and HM-CS6) of different graft types and densities were synthesized, characterized, and packaged into spray canisters using dimethyl ether as the propellant. Expansion profiles of the foams were evaluated in bench testing. Foams were then evaluated in vitro, interaction with blood cells was determined via microscopy, and cytotoxicity was assessed via live-dead cell assay on MCF7 breast cancer cells. For in vivo evaluation, rats underwent a 14 +/- 3% hepatectomy. The animals were treated with either: (1) an HM-CS foam formulation, (2) CS foam, and (3) no treatment (NT). All animals were resuscitated with lactated Ringer solution. Survival, total blood loss, mean arterial pressures (MAP), and resuscitation volume were recorded for 60 min. Results: Microscopy showed blood cells immobilizing into colonies within tight groups of adjacent foam bubbles. HM-CS foam did not display any toxic effects in vitro on MCF7 cells over a 72 h period studied. Application of HM-CS foam after hepatectomy decreased total blood loss (29.3 +/- 7.8mL/kg in HM-CS5 group versus 90.9 +/- 20.3 mL/kg in the control group; P < 0.001) and improved survival from 0% in controls to 100% in the HM-CS5 group (P < 0.001). Conclusions: In this model of severe liver injury, spraying HM-CS foams directly on the injured liver surface decreased blood loss and increased survival. HM-CS formulations with the highest levels of hydrophobic modification (HM-CS4 and HM-CS5) resulted in the lowest total blood loss and highest survival rates. This pilot study suggests HM-CS foam may be useful as a hemostatic adjunct or solitary hemostatic intervention. (C) 2015 Elsevier Inc. All rights reserved. C1 [Dowling, Matthew B.; Harris, Erica; Raghavan, Srinivasa R.] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. [Smith, William; Balogh, Peter; Duggan, Michael J.; Mesar, Tomaz; King, David R.] Massachusetts Gen Hosp, Div Trauma Acute Care Surg & Surg Crit Care, Dept Surg, Boston, MA 08174 USA. [MacIntire, Ian C.; Raghavan, Srinivasa R.] Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20742 USA. RP King, DR (reprint author), Massachusetts Gen Hosp, Div Trauma Acute Care Surg & Surg Crit Care, Boston, MA 02114 USA. EM dking3@partners.org OI King, David/0000-0003-1028-1478 FU NSF SBIR Phase I program [IIP - 1142778] FX This work was funded by the NSF SBIR Phase I program (Award Number IIP - 1142778). The authors also acknowledge Dr Ian White (UMD, Fischell Department of Bioengineering) for the MCF7 cell line and cell culture facilities usage for live-dead cell assays. Furthermore, we acknowledge Samantha Gribben at American Spraytech for packaging the canisters. NR 29 TC 5 Z9 7 U1 7 U2 53 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 EI 1095-8673 J9 J SURG RES JI J. Surg. Res. PD JAN PY 2015 VL 193 IS 1 BP 316 EP 323 DI 10.1016/j.jss.2014.06.019 PG 8 WC Surgery SC Surgery GA AW4HH UT WOS:000346241300041 PM 25016441 ER PT J AU Lin, WM Luo, S Muzikansky, A Lobo, AZC Tanabe, KK Sober, AJ Cosimi, AB Tsao, HS Duncan, LM AF Lin, William M. Luo, Su Muzikansky, Alona Lobo, Alice Z. C. Tanabe, Kenneth K. Sober, Arthur J. Cosimi, A. Benedict Tsao, Hensin Duncan, Lyn M. TI Outcome of patients with de novo versus nevus-associated melanoma SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE dysplastic nevus; melanoma; nevus; overall survival; precursor; sentinel lymph node biopsy ID CUTANEOUS MALIGNANT-MELANOMA; MELANOCYTIC NEVI; HISTOLOGIC ASSOCIATION; LESIONS; HISTOGENESIS; PROGNOSIS; RISK; CLASSIFICATION; THICKNESS; MARKERS AB Background: Prior reports indicate a wide range of melanomas in histopathologic contiguity with a nevus, and an associated nevus has unclear prognostic implications in melanoma. Objective: We sought to investigate the relationship among nevus-associated melanomas, sentinel lymph node status, and overall survival. Methods: We conducted a retrospective analysis of 850 patients with cutaneous melanoma and sentinel lymph node removed at Massachusetts General Hospital from 1998 through 2008 and meta-analysis of the literature. Results: Nevus-associated melanomas represented 28% (235/850) of cases and were significantly correlated with younger age (P = .03), truncal site (P = .0005), superficial spreading type (P < .0001), and absent ulceration (P = .005). There was no association with sentinel lymph node status (P = .94) and no survival difference between nevus-associated versus de novo melanoma (P = .41). Meta-analysis of over 4000 cases revealed a similar percentage of associated nevi (32%). Limitations: This was a retrospective study. Conclusions: Approximately 30% of melanomas are associated with a nevus. The presence of a nevus associated with a melanoma has no prognostic implication in sentinel lymph node status or overall survival. C1 [Lin, William M.; Luo, Su; Sober, Arthur J.; Tsao, Hensin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Muzikansky, Alona] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Lobo, Alice Z. C.; Duncan, Lyn M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. [Lobo, Alice Z. C.; Duncan, Lyn M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dermatopathol Unit, Boston, MA 02114 USA. [Tanabe, Kenneth K.; Cosimi, A. Benedict] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. RP Duncan, LM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dermatopathol Unit, WRN 825,55 Fruit St, Boston, MA 02114 USA. EM duncan@helix.mgh.harvard.edu NR 29 TC 9 Z9 9 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JAN PY 2015 VL 72 IS 1 BP 54 EP 58 DI 10.1016/j.jaad.2014.09.028 PG 5 WC Dermatology SC Dermatology GA AW6UU UT WOS:000346404500030 PM 25440436 ER PT J AU Kimball, AB Rothman, KJ Kricorian, G Pariser, D Yamauchi, PS Menter, A Teller, CF Aras, G Accortt, NA Hooper, M Rice, KC Gelfand, JM AF Kimball, Alexa B. Rothman, Kenneth J. Kricorian, Gregory Pariser, David Yamauchi, Paul S. Menter, Alan Teller, Craig F. Aras, Girish Accortt, Neil A. Hooper, Michele Rice, Kara Creamer Gelfand, Joel M. TI OBSERVE-5: Observational postmarketing safety surveillance registry of etanercept for the treatment of psoriasis final 5-year results SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE adverse events; etanercept; infections; malignancy; plaque psoriasis; registry; safety; surveillance ID RISK AB Background: OBSERVE-5 was a 5-year Food and Drug Administration-mandated surveillance registry of patients with psoriasis. Objective: We sought to assess long-term etanercept safety and effectiveness. Methods: Patients with moderate to severe psoriasis enrolled; a single baseline dose of etanercept was required. Key outcome measures included serious adverse events, serious infectious events, events of medical interest, psoriasis-affected body surface area, physician global assessment score, and Dermatology Life Quality Index score. Safety outcomes were assessed relative to data from the MarketScan database. Results: For 2510 patients, 5-year cumulative incidence was 22.2% (95% confidence interval [CI] 20.3%-24.2%) for serious adverse events; 6.5% (95% CI 5.4%-7.7%) for serious infectious events; 3.2% (95% CI 2.3%-4.1%) for malignancies excluding nonmelanoma skin cancer; 3.6% (95% CI 2.7%-4.5%) for nonmelanoma skin cancer; 2.8% (95% CI 2.0%-3.6%) for coronary artery disease; 0.7% (95% CI 0.3%-1.2%) for psoriasis worsening; 0.2% (95% CI 0.0%-0.4%) for central nervous system demyelinating disorder; 0.1% (95% CI 0.0%-0.3%) for lymphoma and for tuberculosis; and 0.1% (95% CI 0.0%-0.2%) for opportunistic infection and for lupus; 55 fatal events were reported. Rates of malignancies, lymphomas, nonmelanoma skin cancer, and hospitalization-associated infections were not higher than expected relative to administrative claims data. The percentage of patients rated as clear/almost clear was 12% at baseline, which increased to 51% at month 6 and remained relatively stable throughout 5 years. Limitations: No internal comparator group was included; rare events may not have been detected. Conclusion: No new safety signals were observed with long-term, real-world etanercept use. C1 [Kimball, Alexa B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rothman, Kenneth J.] RTI Int, RTI Hlth Solut, Res Triangle Pk, NC USA. [Kricorian, Gregory; Aras, Girish; Accortt, Neil A.; Hooper, Michele; Rice, Kara Creamer] Amgen Inc, Thousand Oaks, CA 91320 USA. [Pariser, David] Eastern Virginia Med Sch, Norfolk, VA USA. [Pariser, David] Virginia Clin Res Inc, Norfolk, VA USA. [Yamauchi, Paul S.] Inst Dermatol, Santa Monica, CA USA. [Yamauchi, Paul S.] Skin Care Ctr, Santa Monica, CA USA. [Menter, Alan] Baylor Res Inst, Dallas, TX USA. [Gelfand, Joel M.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 50 Staniford St,240, Boston, MA 02114 USA. EM harvardskinstudies@partners.org FU Immunex; Amgen Inc; Wyeth FX Funded by Immunex, a wholly owned subsidiary of Amgen Inc, and by Wyeth, which was acquired by Pfizer Inc in October 2009. NR 13 TC 10 Z9 10 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JAN PY 2015 VL 72 IS 1 BP 115 EP 122 DI 10.1016/j.jaad.2014.08.050 PG 8 WC Dermatology SC Dermatology GA AW6UU UT WOS:000346404500039 PM 25264239 ER PT J AU Murrell, DF Marinovic, B Caux, F Prost, C Ahmed, R Wozniak, K Amagai, M Bauer, J Beissert, S Borradori, L Culton, D Fairley, JA Fivenson, D Jonkman, MF Marinkovich, MP Woodley, D Zone, J Aoki, V Bernard, P Bruckner-Tuderman, L Cianchini, G Venning, V Diaz, L Eming, R Grando, SA Hall, RP Hashimoto, T Herrero-Gonzalez, JE Hertl, M Joly, P Karpati, S Kim, J Kim, SC Korman, NJ Kowalewski, C Lee, SE Rubenstein, DR Sprecher, E Yancey, K Zambruno, G Zillikens, D Doan, S Daniel, BS Werth, VP AF Murrell, Dedee F. Marinovic, Branka Caux, Frederic Prost, Catherine Ahmed, Razzaque Wozniak, Katarzyna Amagai, Masayuki Bauer, Johann Beissert, Stefan Borradori, Luca Culton, Donna Fairley, Janet A. Fivenson, David Jonkman, Marcel F. Marinkovich, M. Peter Woodley, David Zone, John Aoki, Valeria Bernard, Philippe Bruckner-Tuderman, Leena Cianchini, Giuseppe Venning, Vanessa Diaz, Luis Eming, Rudiger Grando, Sergei A. Hall, Russell P. Hashimoto, Takashi Herrero-Gonzalez, Josep E. Hertl, Michael Joly, Pascal Karpati, Sarolta Kim, Jaehwan Kim, Soo Chan Korman, Neil J. Kowalewski, Cezary Lee, Sang Eun Rubenstein, David R. Sprecher, Eli Yancey, Kim Zambruno, Giovanna Zillikens, Detlef Doan, Serge Daniel, Benjamin S. Werth, Victoria P. TI Definitions and outcome measures for mucous membrane pemphigoid: Recommendations of an international panel of experts SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Review DE consensus; definitions; mucous membrane pemphigoid; outcome measures; severity score ID CONSENSUS; DISEASE AB Mucous membrane pemphigoid encompasses a group of autoimmune bullous diseases with a similar phenotype characterized by subepithelial blisters, erosions, and scarring of mucous membranes, skin, or both. Although knowledge about autoimmune bullous disease is increasing, there is often a lack of clear definitions of disease, outcome measures, and therapeutic end points. With clearer definitions and outcome measures, it is possible to directly compare the results and data from various studies using meta-analyses. This consensus statement provides accurate and reproducible definitions for disease extent, activity, outcome measures, end points, and therapeutic response for mucous membrane pemphigoid and proposes a disease extent score, the Mucous Membrane Pemphigoid Disease Area Index. C1 [Murrell, Dedee F.; Kim, Jaehwan; Daniel, Benjamin S.] Univ New S Wales, St George Hosp, Dept Dermatol, Sydney, NSW 2317, Australia. [Marinovic, Branka] Univ Zagreb, Dept Dermatol & Venereol, Hosp Ctr & Sch Med, Zagreb 41000, Croatia. [Caux, Frederic] Univ Paris 13, Dept Dermatol, Avicenne Hosp, Bobigny, France. [Prost, Catherine] Univ Paris 13, Dept Dermatol, Dept Histol, Reference Ctr Autoimmune Bullous Dis,Avicenne Hos, Bobigny, France. [Ahmed, Razzaque] Ctr Blistering Dis, Boston, MA USA. [Wozniak, Katarzyna; Kowalewski, Cezary] Med Univ Warsaw, Dept Dermatol & Immunodermatol, Warsaw, Poland. [Amagai, Masayuki] Keio Univ, Sch Med, Dept Dermatol, Tokyo, Japan. [Bauer, Johann] Paracelsus Med Univ Salzburg, Div Mol Dermatol, Dept Dermatol, Salzburg, Austria. [Beissert, Stefan] Univ Dresden, Dept Dermatol, Dresden, Germany. [Borradori, Luca] Univ Hosp Bern, Dept Dermatol, Bern, Switzerland. [Culton, Donna; Diaz, Luis; Rubenstein, David R.] Univ N Carolina, Dept Dermatol, Chapel Hill, NC 27515 USA. [Fairley, Janet A.] Univ Iowa, Dept Dermatol, Iowa City, IA 52242 USA. [Fairley, Janet A.] Dept Vet Affairs Med Ctr, Palo Alto, CA USA. [Fivenson, David] St Joseph Mercy Hlth Syst, Dept Dermatol, Ann Arbor, MI USA. [Jonkman, Marcel F.] Univ Groningen, Univ Med Ctr Groningen, NL-9700 AB Groningen, Netherlands. [Marinkovich, M. Peter] Stanford Univ, Dept Dermatol, Sch Med, Stanford, CA 94305 USA. [Marinkovich, M. Peter] Dept Vet Affairs Palo Alto Healthcare Syst, Ctr Clin Sci Res, Palo Alto, CA USA. [Marinkovich, M. Peter] Dept Vet Affairs Palo Alto Healthcare Syst, Div Dermatol, Palo Alto, CA USA. [Woodley, David] Univ So Calif, Keck Sch Med, Dept Dermatol, Los Angeles, CA 90033 USA. [Zone, John] Univ Utah, Dept Dermatol, Sch Med, Salt Lake City, UT 84112 USA. [Aoki, Valeria] Univ Sao Paulo, Dept Dermatol, BR-05508 Sao Paulo, Brazil. [Bernard, Philippe] Univ Champagne Ardenne, Reims Univ Hosp, Dept Dermatol, Reims, France. [Bruckner-Tuderman, Leena] Univ Freiburg, Med Ctr, Dept Dermatol, Freiburg, Germany. [Cianchini, Giuseppe; Zambruno, Giovanna] IRCCS, Ist Dermopat Immacolata, Dept Immunodermatol, Rome, Italy. [Cianchini, Giuseppe] IRCCS, Ist Dermopat Immacolata, Lab Mol & Cell Biol, Rome, Italy. [Venning, Vanessa] Churchill Hosp, Dept Dermatol, Oxford OX3 7LJ, England. [Eming, Rudiger] Univ Marburg, Dept Dermatol & Allergol, Univ Hosp, D-35032 Marburg, Germany. [Grando, Sergei A.] Univ Calif Irvine, Dept Dermatol, Irvine, CA 92717 USA. [Grando, Sergei A.] Univ Calif Irvine, Dept Biol Chem, Ctr Canc, Irvine, CA 92717 USA. [Grando, Sergei A.] Univ Calif Irvine, Inst Immunol, Res Inst, Irvine, CA 92717 USA. [Hall, Russell P.] Duke Med Ctr, Div Dermatol, Durham, NC USA. [Hashimoto, Takashi] Kurume Univ, Sch Med, Kurume, Fukuoka, Japan. [Herrero-Gonzalez, Josep E.] Inst Hosp Mar Invest Med, Hosp del Mar, Dept Dermatol, Barcelona, Spain. [Hertl, Michael] Univ Hosp, Dept Dermatol, Marburg, Germany. [Joly, Pascal] Rouen Univ Hosp, INSERM U905, INSERM, Dermatol Clin, Rouen, France. [Joly, Pascal] Univ Rouen, Dept Dermatol, Rouen Univ Hosp, F-76821 Mont St Aignan, France. [Karpati, Sarolta] Semmelweis Univ, Dept Dermatol Venereol & Dermatooncol, H-1085 Budapest, Hungary. [Kim, Jaehwan] Rockefeller Univ, Invest Dermatol Lab, New York, NY 10021 USA. [Kim, Soo Chan] Yonsei Univ, Coll Med, Gangnam Severance Hosp, Dept Dermatol, Seoul, South Korea. [Kim, Soo Chan] Yonsei Univ, Coll Med, Gangnam Severance Hosp, Cutaneous Biol Res Inst, Seoul, South Korea. [Korman, Neil J.] Univ Hosp Case Med Ctr, Dept Dermatol, Cleveland, OH USA. [Korman, Neil J.] Univ Hosp Case Med Ctr, Murdough Family Ctr Psoriasis, Cleveland, OH USA. [Lee, Sang Eun] CHA Univ, Dept Dermatol, CHA Bundang Med Ctr, Songnam, South Korea. [Sprecher, Eli] Tel Aviv Sourasky Med Ctr, Dept Dermatol, Tel Aviv, Israel. [Yancey, Kim] Univ Texas Southwestern Med Ctr, Dept Dermatol, Dallas, TX USA. [Zillikens, Detlef] Univ Lubeck, Dept Dermatol, Lubeck, Germany. [Doan, Serge] Hop Bichat Claude Bernard, Dept Ophthalmol, Paris, France. [Doan, Serge] Fdn Adolphe De Rothschild, Paris, France. [Werth, Victoria P.] Univ Penn, Philadelphia Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Werth, Victoria P.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. RP Murrell, DF (reprint author), Univ New S Wales, St George Hosp, Dept Dermatol, Gray St,N8W, Sydney, NSW 2317, Australia. EM d.murrell@unsw.edu.au RI Amagai, Masayuki/K-5325-2013; Zillikens, Detlef/C-8572-2011; Aoki, Valeria/H-1415-2012; OI Amagai, Masayuki/0000-0003-3314-7052; Marinovic, Branka/0000-0001-8441-5016; Hashimoto, Takashi/0000-0002-0144-3255 FU Department of Veterans Affairs (Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development); National Institutes of Health [NIH K24-AR 02207] FX The International Pemphigus and Pemphigoid Foundation generously supported hiring rooms at the Annual Meetings of the American Academy of Dermatology and European Academy of Dermatology and Venereology as well as audiovisual equipment and open access. The Korean World Congress Committee and the Society for Investigative Dermatology provided meeting rooms. This material is based on work supported by the Department of Veterans Affairs (Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development) and by the National Institutes of Health (NIH K24-AR 02207) to Dr Werth. NR 9 TC 14 Z9 14 U1 3 U2 10 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JAN PY 2015 VL 72 IS 1 BP 168 EP 174 DI 10.1016/j.jaad.2014.08.024 PG 7 WC Dermatology SC Dermatology GA AW6UU UT WOS:000346404500046 PM 25443626 ER PT J AU Nambudiri, VE Solus, JF Staszewski, R Winkfield, KM Duncan, LM Nazarian, RM Carter, JB AF Nambudiri, Vinod E. Solus, Jason F. Staszewski, Robert Winkfield, Karen M. Duncan, Lyn M. Nazarian, Rosalynn M. Carter, Joi B. TI Isolated nodule on the ear SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Editorial Material C1 [Nambudiri, Vinod E.; Staszewski, Robert; Carter, Joi B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Winkfield, Karen M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Solus, Jason F.; Duncan, Lyn M.; Nazarian, Rosalynn M.] Massachusetts Gen Hosp, Dermatopathol Unit, Pathol Serv, Boston, MA 02114 USA. [Nambudiri, Vinod E.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Staszewski, Robert] Boston Dermatol & Laser Ctr, Boston, MA USA. RP Nambudiri, VE (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM vnambudiri@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JAN PY 2015 VL 72 IS 1 BP E21 EP E22 DI 10.1016/j.jaad.2014.06.041 PG 2 WC Dermatology SC Dermatology GA AW6UU UT WOS:000346404500011 PM 25497940 ER PT J AU Bloom, MB Raza, S Bhakta, A Ewing, T Patel, M Ley, EJ Margulies, DR Salim, A Malinoski, D AF Bloom, Matthew B. Raza, Shariq Bhakta, Akash Ewing, Tyler Patel, Madhukar Ley, Eric J. Margulies, Daniel R. Salim, Ali Malinoski, Darren TI Impact of Deceased Organ Donor Demographics and Critical Care End Points on Liver Transplantation and Graft Survival Rates SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article; Proceedings Paper CT PROMMTT Symposium held at the 71st Annual Meeting of the American-Association-for-the-Surgery-of-Trauma (AAST) / Clinical Congress of Acute Care Surgery CY SEP 12-15, 2012 CL HI SP Amer Assoc Surg Trauma ID BODY-MASS INDEX; MANAGEMENT GOALS; SERUM SODIUM; RISK INDEX; CRITERIA; AGE; PATIENT; HYPERNATREMIA; NONFUNCTION; EXPERIENCE AB BACKGROUND: The criteria for organ acceptance remain inconsistent, which limits the ability to standardize critical care practices. We sought to examine predictors of liver graft use and survival to better guide the selection and management of potential organ donors. STUDY DESIGN: A prospective observational study of all donors managed by the 8 organ procurement organizations in United Network for Organ Sharing Region 5 was conducted from July 2008 to March 2011. Critical care end points that reflect the normal hemodynamic, acid-base, respiratory, endocrine, and renal status of the donor were collected at 3 time points. Critical care and demographic data associated with liver transplantation and graft survival rates were first determined using univariate analyses, and then logistic regression was used to identify independent predictors of these two outcomes. RESULTS: From 961 donors, 730 (76%) livers were transplanted and 694 (95%) were functioning after 74 +/- 73 days of follow-up. After regression analysis, donor BMI (odds ratio [OR] = 0.94), male sex (OR = 1.89), glucose < 150 mg/dL (OR = 1.97), lower dopamine dose (OR = 0.95), vasopressin use (OR = 1.95), and ejection fraction >50% (OR = 1.77) remained as independent predictors of liver use. Graft survival was associated with lower donor BMI (OR = 0.91) and sodium levels (OR = 0.95). CONCLUSIONS: After controlling for donor age, sex, and BMI, both hemodynamic and endocrine critical care end points were associated with increased liver graft use. Both donor BMI and lower sodium levels during the course of donor management were independently predictive of improved graft survival. These results may help guide the management and selection of potential organ donors after neurologic determination of death. ((C) 2015 by the American College of Surgeons) C1 [Bloom, Matthew B.; Ley, Eric J.; Margulies, Daniel R.] Cedars Sinai Med Ctr, Dept Surg, Los Angeles, CA 90048 USA. [Ewing, Tyler] Univ Calif Davis, Sch Med, Davis, CA 95616 USA. [Raza, Shariq] Temple Univ, Med Ctr, Dept Surg, Philadelphia, PA 19122 USA. [Bhakta, Akash] Midwestern Univ, Glendale, AZ USA. [Patel, Madhukar] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Salim, Ali] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Malinoski, Darren] Portland VA Med Ctr, Surg Crit Care Sect, Portland, OR USA. [Malinoski, Darren] Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97201 USA. RP Malinoski, D (reprint author), Portland VA Med Ctr, POB 1034-P3SURG, Portland, OR 97207 USA. EM Darren.malinoski@va.gov NR 37 TC 4 Z9 4 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JAN PY 2015 VL 220 IS 1 BP 38 EP 47 DI 10.1016/j.jamcollsurg.2014.09.020 PG 10 WC Surgery SC Surgery GA AW6ER UT WOS:000346362800006 PM 25458800 ER PT J AU Chen, BJ Zhou, XH Chan, G AF Chen, Baojiang Zhou, Xiao-Hua Chan, Gary TI Pseudoempirical-likelihood-based method using calibration for longitudinal data with dropout SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE Calibration; Dropout; Empirical likelihood; Longitudinal data ID GENERALIZED ESTIMATING EQUATIONS; IN-COVARIABLES MODELS; EMPIRICAL-LIKELIHOOD; REGRESSION-MODELS; LINEAR-MODELS; AUXILIARY INFORMATION; VALIDATION DATA; RESPONSE DATA; INFERENCE AB In observational studies, interest mainly lies in estimation of the population level relationship between the explanatory variables and dependent variables, and the estimation is often undertaken by using a sample of longitudinal data. In some situations, the longitudinal data sample features biases and loss of estimation efficiency due to non-random dropout. However, inclusion of population level information can increase estimation efficiency. We propose an empirical-likelihood-based method to incorporate population level information in a longitudinal study with dropout. The population level information is incorporated via constraints on functions of the parameters, and non-random dropout bias is corrected by using a weighted generalized estimating equations method. We provide a three-step estimation procedure that makes computation easier. Some commonly used methods are compared in simulation studies, which demonstrate that our proposed method can correct the non-random dropout bias and increase the estimation efficiency, especially for small sample sizes or when the missing proportion is high. In some situations, the improvement in efficiency is substantial. Finally, we apply the method to an Alzheimer's disease study. C1 [Chen, Baojiang] Univ Nebraska Med Ctr, Omaha, NE 68198 USA. [Zhou, Xiao-Hua; Chan, Gary] Univ Washington, Seattle, WA 98195 USA. [Zhou, Xiao-Hua] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Chen, BJ (reprint author), Univ Nebraska Med Ctr, Dept Biostat, Omaha, NE 68198 USA. EM baojiang.chen@unmc.edu FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Research Career Scientist award [RCS 05-196]; National Institute on Aging [U01AG016976] FX The authors thank the Joint Editor, Associate Editor and two referees for their constructive comments and suggestions. Dr Xiao-Hua Zhou is at present a Core Investigator and Biostatistics Unit Director at the Northwest Health Services Research and Development Center of Excellence, Department of Veterans Affairs Medical Center, Seattle. Dr Zhou was supported in part by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Research Career Scientist award RCS 05-196. Both Dr Zhou and Dr Chen were supported in part by National Institute on Aging grant U01AG016976. This paper presents the findings and conclusions of the authors. It does not necessarily represent those of the Veterans Affairs Health Services Research and Development Service. NR 27 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0035-9254 EI 1467-9876 J9 J R STAT SOC C-APPL JI J. R. Stat. Soc. Ser. C-Appl. Stat. PD JAN PY 2015 VL 64 IS 1 BP 157 EP 174 DI 10.1111/rssc.12063 PG 18 WC Statistics & Probability SC Mathematics GA AW8FO UT WOS:000346496700007 PM 25587200 ER PT J AU Aranyosi, AJ Wong, EA Irimia, D AF Aranyosi, Alexander J. Wong, Elisabeth A. Irimia, Daniel TI A neutrophil treadmill to decouple spatial and temporal signals during chemotaxis SO LAB ON A CHIP LA English DT Article ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; CHEMICAL GRADIENTS; MICROFLUIDIC CHANNELS; CELLULAR MEMORY; CHEMOATTRACTANT; MIGRATION; LEUKOTRIENE-B4; ORIENTATION; CONFINEMENT; ATTRACTANT AB After more than 50 years of debates, the role of spatial and temporal gradients during cell chemotaxis is still a contentious matter. One major challenge is that when cells move in response to a heterogeneous chemical environment they are exposed to both spatial and temporal concentration changes. Even in the presence of perfectly stable chemical gradients, moving cells experience temporal changes of concentration simply by moving between locations with different chemical concentrations in a heterogeneous environment. Thus, the effects of the spatial and temporal stimuli cannot be dissociated and studied independently, hampering progress towards understanding the mechanisms of cell chemotaxis. Here we employ microfluidic and other engineering tools to build a system that accomplishes a function analogous to a treadmill at the cellular scale, holding a moving cell at a specified, unchanging location in a chemical gradient. Using this system, we decouple the spatial and temporal gradients around moving human neutrophils and find that temporal gradients are necessary for the directional persistence of human neutrophils during chemotaxis. Our results suggest that temporal chemoattractant changes are important during neutrophil migration and should be taken into account when deciphering the signalling pathways of cell chemotaxis. C1 [Aranyosi, Alexander J.; Wong, Elisabeth A.; Irimia, Daniel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, BioMEMS Resource Ctr,Dept Surg, Charlestown, MA 02129 USA. RP Irimia, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, BioMEMS Resource Ctr,Dept Surg, Charlestown, MA 02129 USA. EM dirimia@hms.harvard.edu OI Aranyosi, Alexander/0000-0002-8133-5026; Irimia, Daniel/0000-0001-7347-2082 FU BioMEMS Resource Center (National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering grant) [EB002503]; National Institutes of Health (National Institute of General Medical Sciences) [GM092804]; National Institutes of Health (National Institute of Allergy and Infectious Diseases) [AI076760] FX All fabrication procedures were performed at the BioMEMS Resource Center (National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering grant EB002503). Funding was provided in part from National Institutes of Health (National Institute of General Medical Sciences - grant GM092804 and National Institute of Allergy and Infectious Diseases - grant AI076760). NR 46 TC 3 Z9 3 U1 1 U2 5 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 2015 VL 15 IS 2 BP 549 EP 556 DI 10.1039/c4lc00970c PG 8 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA AW7YL UT WOS:000346477500020 PM 25412288 ER PT J AU Orbai, AM Truedsson, L Sturfelt, G Nived, O Fang, H Alarcon, GS Gordon, C Merrill, JT Fortin, PR Bruce, IN Isenberg, DA Wallace, DJ Ramsey-Goldman, R Bae, SC Hanly, JG Sanchez-Guerrero, J Clarke, AE Aranow, CB Manzi, S Urowitz, MB Gladman, DD Kalunian, KC Costner, MI Werth, VP Zoma, A Bernatsky, S Ruiz-Irastorza, G Khamashta, MA Jacobsen, S Buyon, JP Maddison, P Dooley, MA Van Vollenhoven, RF Ginzler, E Stoll, T Peschken, C Jorizzo, JL Callen, JP Lim, SS Fessler, BJ Inanc, M Kamen, DL Rahman, A Steinsson, K Franks, AG Sigler, L Hameed, S Pham, N Brey, R Weisman, MH McGwin, G Magder, LS Petri, M AF Orbai, A-M Truedsson, L. Sturfelt, G. Nived, O. Fang, H. Alarcon, G. S. Gordon, C. Merrill, J. T. Fortin, P. R. Bruce, I. N. Isenberg, D. A. Wallace, D. J. Ramsey-Goldman, R. Bae, S-C Hanly, J. G. Sanchez-Guerrero, J. Clarke, A. E. Aranow, C. B. Manzi, S. Urowitz, M. B. Gladman, D. D. Kalunian, K. C. Costner, M. I. Werth, V. P. Zoma, A. Bernatsky, S. Ruiz-Irastorza, G. Khamashta, M. A. Jacobsen, S. Buyon, J. P. Maddison, P. Dooley, M. A. Van Vollenhoven, R. F. Ginzler, E. Stoll, T. Peschken, C. Jorizzo, J. L. Callen, J. P. Lim, S. S. Fessler, B. J. Inanc, M. Kamen, D. L. Rahman, A. Steinsson, K. Franks, A. G., Jr. Sigler, L. Hameed, S. Pham, N. Brey, R. Weisman, M. H. McGwin, G., Jr. Magder, L. S. Petri, M. TI Anti-C1q antibodies in systemic lupus erythematosus SO LUPUS LA English DT Article DE Anti-dsDNA antibodies; renal lupus; systemic lupus erythematosus ID RENAL-DISEASE ACTIVITY; COLLAGEN-LIKE REGION; AUTOIMMUNE-DISEASES; PREDICTIVE-VALUE; IMMUNE DEPOSITS; C1Q DEFICIENCY; NEPHRITIS; AUTOANTIBODIES; COMPLEMENT; SERA AB Objective Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs rheumatic disease controls) and the association with SLE manifestations in an international multicenter study. Methods Information and blood samples were obtained in a cross-sectional study from patients with SLE (n=308) and other rheumatologic diseases (n=389) from 25 clinical sites (84% female, 68% Caucasian, 17% African descent, 8% Asian, 7% other). IgG anti-C1q against the collagen-like region was measured by ELISA. Results Prevalence of anti-C1q was 28% (86/308) in patients with SLE and 13% (49/389) in controls (OR=2.7, 95% CI: 1.8-4, p<0.001). Anti-C1q was associated with proteinuria (OR=3.0, 95% CI: 1.7-5.1, p<0.001), red cell casts (OR=2.6, 95% CI: 1.2-5.4, p=0.015), anti-dsDNA (OR=3.4, 95% CI: 1.9-6.1, p<0.001) and anti-Smith (OR=2.8, 95% CI: 1.5-5.0, p=0.01). Anti-C1q was independently associated with renal involvement after adjustment for demographics, ANA, anti-dsDNA and low complement (OR=2.3, 95% CI: 1.3-4.2, p<0.01). Simultaneously positive anti-C1q, anti-dsDNA and low complement was strongly associated with renal involvement (OR=14.9, 95% CI: 5.8-38.4, p<0.01). Conclusions Anti-C1q was more common in patients with SLE and those of Asian race/ethnicity. We confirmed a significant association of anti-C1q with renal involvement, independent of demographics and other serologies. Anti-C1q in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis. C1 [Orbai, A-M; Fang, H.; Sigler, L.; Hameed, S.; Pham, N.; Petri, M.] Johns Hopkins Univ, Sch Med, Div Rheumatol, Baltimore, MD 21218 USA. [Truedsson, L.] Lund Univ, Dept Lab Med, Sect Microbiol Immunol & Glycobiol, Lund, Sweden. [Sturfelt, G.; Nived, O.] Skane Univ Hosp, Dept Rheumatol, Lund, Sweden. [Alarcon, G. S.; Fessler, B. J.; McGwin, G., Jr.] Univ Alabama Birmingham, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Gordon, C.] Univ Birmingham, Rheumatol Res Grp, Sch Immun & Infect, Coll Med & Dent Sci, Birmingham, W Midlands, England. [Merrill, J. T.] Oklahoma Med Res Fdn, Dept Clin Pharmacol, Oklahoma City, OK 73104 USA. [Fortin, P. R.] Univ Laval, Dept Med, Ctr Hosp Univ CHU Quebec Axe Malad Infect & Immun, Div Rheumatol,CRCHU Quebec, Quebec City, PQ G1K 7P4, Canada. [Bruce, I. N.] Univ Manchester, Manchester Acad Hlth Sci Ctr, Arthrit Res UK Ctr Epidemiol, Ctr Musculoskeletal Res,Inst Inflammat & Repair, Manchester, Lancs, England. [Bruce, I. N.; Rahman, A.] Cent Manchester Univ Hosp NHS Fdn Trust, NIHR Manchester Musculoskeletal Biomed Res Unit, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Isenberg, D. A.] Ctr Rheumatol, Div Med Res, London, England. [Wallace, D. J.] Univ Calif Los Angeles, David Geffen Sch Med, Cedars Sinai Med Ctr, Los Angeles, CA 90095 USA. [Ramsey-Goldman, R.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Bae, S-C] Hanyang Univ Hosp Rheumat Dis, Dept Rheumatol, Seoul, South Korea. [Hanly, J. G.] Capital Hlth, Dept Med, Div Rheumatol, Halifax, NS, Canada. [Hanly, J. G.] Capital Hlth, Dept Pathol, Div Rheumatol, Halifax, NS, Canada. [Hanly, J. G.] Dalhousie Univ, Halifax, NS, Canada. [Sanchez-Guerrero, J.] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Sanchez-Guerrero, J.] Univ Hlth Network, Toronto, ON, Canada. [Clarke, A. E.; Bernatsky, S.] McGill Univ, Ctr Hlth, Div Clin Epidemiol, Montreal, PQ, Canada. [Clarke, A. E.; Bernatsky, S.] McGill Univ, Ctr Hlth, Div Rheumatol, Montreal, PQ, Canada. [Aranow, C. B.] Feinstein Inst Med Res, Manhasset, NY USA. [Manzi, S.] Allegheny Gen Hosp, Allegheny Singer Res Inst, Div Rheumatol, Dept Med, Pittsburgh, PA 15212 USA. [Urowitz, M. B.; Gladman, D. D.] Toronto Western Hosp, Toronto, ON M5T 2S8, Canada. [Kalunian, K. C.] UCSD Sch Med, Div Rheumatol Allergy & Immunol, La Jolla, CA USA. [Costner, M. I.] North Dallas Dermatol Associates, Dallas, TX USA. [Werth, V. P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Werth, V. P.] Univ Penn, Philadelphia, PA 19104 USA. [Zoma, A.] Lanarkshire Ctr Rheumatol, E Kilbride, Lanark, Scotland. [Zoma, A.] Hairmyres Hosp, E Kilbride, Lanark, Scotland. [Ruiz-Irastorza, G.] Univ Basque Country, Hosp Univ Cruces, Autoimmune Dis Res Unit, Baracaldo, Spain. [Khamashta, M. A.] Rayne Inst, London, England. [Khamashta, M. A.] St Thomas Hosp London, London, England. [Jacobsen, S.] Copenhagen Univ Hosp, Rigshosp, Copenhagen, Denmark. [Buyon, J. P.; Franks, A. G., Jr.] NYU, New York, NY USA. [Maddison, P.] Ysbyty Gwynedd, Bangor, Gwynedd, Wales. [Dooley, M. A.] Univ N Carolina, Chapel Hill, NC USA. [Van Vollenhoven, R. F.] Karolinska Univ Hosp, Stockholm, Sweden. [Ginzler, E.] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. [Stoll, T.] Kantonsspital Schaffhausen, Schaffhausen, Switzerland. [Peschken, C.] Univ Manitoba Winnipeg, Winnipeg, MB, Canada. [Jorizzo, J. L.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Callen, J. P.] Univ Louisville, Louisville, KY 40292 USA. [Lim, S. S.] Emory Univ, Atlanta, GA 30322 USA. [Inanc, M.] Istanbul Univ, Istanbul Fac Med, Dept Internal Med, Div Rheumatol, Istanbul, Turkey. [Kamen, D. L.] Med Univ S Carolina, Charleston, SC 29425 USA. [Steinsson, K.] Landspitali Univ Hosp, Reykjavik, Iceland. [Brey, R.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Weisman, M. H.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Magder, L. S.] Univ Maryland, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. RP Petri, M (reprint author), Johns Hopkins Univ, Sch Med, Div Rheumatol, 1830 E Monument St,Suite 7500, Baltimore, MD 21218 USA. EM MPetri@jhmi.edu RI Ruiz-Irastorza, Guillermo/P-7058-2014; OI Ruiz-Irastorza, Guillermo/0000-0001-7788-1043; Peschken, Christine/0000-0002-4269-5213; Isenberg, David/0000-0001-9514-2455; Franks, Andrew/0000-0001-5427-6369 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); Lupus Foundation of America; Human Genome Sciences; National Institutes of Health (NIH) [T32 AR048522]; Greta and Johan Kock's Foundation; King Gustaf V's 80th Birthday Foundation; Swedish Rheumatism Association; Lupus UK; Canada Research Chair on Systemic Autoimmune Rheumatic Diseases; National Institute for Health Research University College London Hospitals Biomedical Research Centre; Korea Healthcare Technology R & D Project, Ministry for Health and Welfare, Republic of Korea [A120404]; Arthritis Research UK; Manchester Academic Health Science Centre; NIHR Manchester Musculoskeletal Biomedical Research Unit; NIHR Manchester Wellcome Trust Clinical Research Facility; Manchester Biomedical Research Centre FX This work was supported in the form of grants or industrial support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and Lupus Foundation of America, and an unrestricted research grant from Human Genome Sciences.; Dr Ana-Maria Orbai is supported by National Institutes of Health (NIH) grant T32 AR048522.; Dr Gunnar Sturfelt and Dr Lennart Truedsson are supported by grants from the Greta and Johan Kock's Foundation, King Gustaf V's 80th Birthday Foundation and the Swedish Rheumatism Association.; Dr Caroline Gordon is supported by Lupus UK.; Dr Paul R. Fortin is supported by a Canada Research Chair on Systemic Autoimmune Rheumatic Diseases.; Dr David A. Isenberg and Dr Anisur Rahman are supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre.; Dr Sang-Cheol Bae is supported by the Korea Healthcare Technology R & D Project, Ministry for Health and Welfare, Republic of Korea (A120404).; Professor I. Bruce is a National Institute for Health Research (NIHR) Senior Investigator and is supported by Arthritis Research UK, The Manchester Academic Health Science Centre, the NIHR Manchester Musculoskeletal Biomedical Research Unit, The NIHR Manchester Wellcome Trust Clinical Research Facility and the Manchester Biomedical Research Centre. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. NR 33 TC 22 Z9 22 U1 0 U2 14 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0961-2033 EI 1477-0962 J9 LUPUS JI Lupus PD JAN PY 2015 VL 24 IS 1 BP 42 EP 49 DI 10.1177/0961203314547791 PG 8 WC Rheumatology SC Rheumatology GA AW3HR UT WOS:000346177700006 PM 25124676 ER PT J AU Regensteiner, JG Bauer, TA Huebschmann, AG Herlache, L Weinberger, HD Wolfel, EE Reusch, JEB AF Regensteiner, Judith G. Bauer, Timothy A. Huebschmann, Amy G. Herlache, Leah Weinberger, Howard D. Wolfel, Eugene E. Reusch, Jane E. B. TI Sex Differences in the Effects of Type 2 Diabetes on Exercise Performance SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE OXYGEN CONSUMPTION; OXYGEN UPTAKE KINETICS; FUNCTIONAL IMPAIRMENT; CARDIOVASCULAR ID SOCIETY-OF-ECHOCARDIOGRAPHY; OXYGEN-UPTAKE; DOPPLER-ECHOCARDIOGRAPHY; CARDIOVASCULAR-DISEASE; FILLING PRESSURES; VASCULAR-DISEASE; RISK-FACTORS; MELLITUS; WOMEN; MEN AB Purpose People with uncomplicated type 2 diabetes (T2D) have impaired peak exercise performance compared with that of their nondiabetic counterparts. This impairment may represent the earliest indication of cardiovascular (CV) abnormalities in T2D. Women with T2D are known to have worse CV outcomes than those in men with T2D. We hypothesized that women with diabetes have a greater exercise impairment than that in men with diabetes compared with that in their nondiabetic counterparts. Methods We studied 15 women (premenopausal) and 14 men with T2D as well as their nondiabetic counterparts (22 women and 13 men). Exercise testing was performed. Additional outcomes included measurements of insulin sensitivity, endothelial function, blood flow, and resting cardiac function. Results Men and women with T2D but not controls had impaired insulin sensitivity. Women with T2D had a lower peak oxygen consumption (VO2peak) compared with that of nondiabetic women (24%, P < 0.05) than men with diabetes compared with that in nondiabetic men (16%, P < 0.05) (P value between groups < 0.05). The time constants (phase 2) of the VO2 kinetic response tended to be slower in men and women with T2D than those in nondiabetic controls (P = 0.08). There were no differences in resting ventricular function by Doppler echocardiography techniques between groups. Women with T2D had significantly lower flow-mediated dilation and blood flow responses to hyperemia than those in nondiabetic women (both P < 0.05), whereas men with T2D had lower flow-mediated dilation but not lower blood flow than those in nondiabetic men. Conclusions Although both men and women with uncomplicated T2D had a lower VO2peak, the abnormality in women with T2D compared with that in nondiabetic women was greater than that seen in men. Because VO2peak has a strong inverse correlation with mortality, sex disparities observed in exercise capacity among people with T2D suggest a possible rationale for the increased CV morbidity and mortality observed in women compared with those observed in men with uncomplicated T2D. C1 [Regensteiner, Judith G.; Bauer, Timothy A.; Huebschmann, Amy G.; Herlache, Leah] Univ Colorado, Div Internal Med, Sch Med, Dept Med, Aurora, CO USA. [Regensteiner, Judith G.; Weinberger, Howard D.; Wolfel, Eugene E.] Univ Colorado, Div Cardiol, Sch Med, Dept Med, Aurora, CO USA. [Regensteiner, Judith G.; Huebschmann, Amy G.; Reusch, Jane E. B.] Univ Colorado, Ctr Womens Hlth Res, Sch Med, Dept Med, Aurora, CO USA. [Reusch, Jane E. B.] Univ Colorado, Div Endocrinol, Sch Med, Aurora, CO USA. [Weinberger, Howard D.] Natl Jewish Hlth, Div Cardiol, Dept Med, Denver, CO USA. [Reusch, Jane E. B.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Regensteiner, JG (reprint author), Univ Colorado, Ctr Womens Hlth Res, Sch Med, Mail Stop B180,Bldg AO1,12631 East 17th Ave, Aurora, CO 80045 USA. EM judy.regensteiner@ucdenver.edu FU American Diabetes Association; National Institutes of Health/National Center for Research Resources Colorado CTSI [UL1 RR025780] FX This research was funded by a clinical research grant from the American Diabetes Association. The research was also supported by the National Institutes of Health/National Center for Research Resources Colorado CTSI grant number UL1 RR025780. The electrodes for the study were provided by Vermed. NR 42 TC 5 Z9 5 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD JAN PY 2015 VL 47 IS 1 BP 58 EP 65 DI 10.1249/MSS.0000000000000371 PG 8 WC Sport Sciences SC Sport Sciences GA AW6BP UT WOS:000346354800009 PM 24811327 ER PT J AU Roche, AM Richard, AL Rahkola, JT Janoff, EN Weiser, JN AF Roche, A. M. Richard, A. L. Rahkola, J. T. Janoff, E. N. Weiser, J. N. TI Antibody blocks acquisition of bacterial colonization through agglutination SO MUCOSAL IMMUNOLOGY LA English DT Article ID INFLUENZAE TYPE-B; INVASIVE PNEUMOCOCCAL DISEASE; STREPTOCOCCUS-PNEUMONIAE; CONJUGATE VACCINES; POLYSACCHARIDE; IMMUNOGLOBULIN; PROTECTION; INFECTION; IMMUNIZATION; PROTEINS AB Invasive infection often begins with asymptomatic colonization of mucosal surfaces. A murine model of bacterial colonization with Streptococcus pneumoniae was used to study the mechanism for mucosal protection by immunoglobulin. In previously colonized immune mice, bacteria were rapidly sequestered within large aggregates in the nasal lumen. To further examine the role of bacterial agglutination in protection by specific antibodies, mice were passively immunized with immunoglobulinG(IgG) purified from antipneumococcal sera or pneumococcal type-specific monoclonal human IgA (hIgA1 or hIgA2). Systemically delivered IgG accessed the mucosal surface and blocked acquisition of colonization and transmission between littermates. Optimal protection by IgG was independent of Fc fragment and complement and, therefore, did not involve an opsonophagocytic mechanism. Enzymatic digestion or reduction of IgG before administration showed that protection required divalent binding that maintained its agglutinating effect. Divalent hIgA1 is cleaved by the pneumococcal member of a family of bacterial proteases that generate monovalent Faba fragments. Thus, passive immunization with hIgA1 blocked colonization by an IgA1-protease-deficient mutant (agglutinated) but not the protease-producing wild-type parent (not agglutinated), whereas protease-resistant hIgA2 agglutinated and blocked colonization by both. Our findings highlight the importance of agglutinating antibodies in mucosal defense and reveal how successful pathogens evade this effect. C1 [Roche, A. M.; Richard, A. L.; Weiser, J. N.] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. [Rahkola, J. T.; Janoff, E. N.] Univ Colorado Denver, Div Infect Dis, Mucosal & Vaccine Res Program Colorado MAVRC, Aurora, CO USA. [Rahkola, J. T.; Janoff, E. N.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Weiser, JN (reprint author), Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. EM weiser@mail.med.upenn.edu FU US Public Health Service [AI38446, AI05168, AI092468, AI108479]; Robert Austrian Research Award in Pneumococcal Vaccinology; NIH/NIDDK Center for Molecular Studies in Digestive and Liver Diseases [P30-DK050306]; Molecular Pathology and Imaging core facilities; Mucosal and Vaccine Research Program Colorado (MAVRC) FX We thank Jan Erikson from The Wistar Institute for providing X31 Influenza virus. This work was supported by the US Public Health Service, grant number AI38446 and AI05168 (J.N.W.), AI092468 and AI108479 (E.N.J), and the Robert Austrian Research Award in Pneumococcal Vaccinology (A.M.R). Additional support was provided by the NIH/NIDDK Center for Molecular Studies in Digestive and Liver Diseases (P30-DK050306) and its Molecular Pathology and Imaging core facilities, and the Mucosal and Vaccine Research Program Colorado (MAVRC). NR 35 TC 18 Z9 18 U1 3 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 EI 1935-3456 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD JAN PY 2015 VL 8 IS 1 BP 176 EP 185 DI 10.1038/mi.2014.55 PG 10 WC Immunology SC Immunology GA AW5TB UT WOS:000346335600016 PM 24962092 ER PT J AU Malik, R Irodenko, V Zimmermann, L Green, A Layzer, R AF Malik, Rabia Irodenko, Viktoriya Zimmermann, Lara Green, Ari Layzer, Robert TI FOCAL AMYOTROPHY IN MULTIPLE SCLEROSIS SO MUSCLE & NERVE LA English DT Article DE amyotrophy; axonal; demyelination; multiple sclerosis; spinal cord ID CONGENITAL MUSCULAR-DYSTROPHY; CHOLINE KINASE BETA; MUTATIONS; MITOCHONDRIA; MYOPATHIES AB Introduction: The assumption that multiple sclerosis (MS) is purely a white matter disease has been challenged in recent years by observations of axonal damage and neuronal loss in gray matter of the cortex, subcortex, and spinal cord. Methods: We report the case of a 71-year-old man with primary progressive MS and longstanding right arm weakness who presented with intermittent right arm pain. Results: Neurological examination showed atrophy, weakness, and hyporeflexia, and electromyography (EMG) showed acute and chronic partial denervation in multiple segments of the right arm. Magnetic resonance imaging (MRI) demonstrated asymmetric volume loss and increased T2 signal in the right anterior spinal cord from C3 to C7, with no evidence of nerve root compression. Conclusions: Lower motor neuron involvement of his right arm was caused by MS with involvement of either the anterior horn cells or the intraspinal motor nerve roots. C1 [Malik, Rabia; Irodenko, Viktoriya; Zimmermann, Lara; Green, Ari; Layzer, Robert] Univ Calif San Francisco, Dept Neurol, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. RP Malik, R (reprint author), Univ Calif San Francisco, Dept Neurol, San Francisco VA Med Ctr, 505 Parnassus Ave,Box 0114,M-798, San Francisco, CA 94143 USA. EM rabia.mk@gmail.com NR 12 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0148-639X EI 1097-4598 J9 MUSCLE NERVE JI Muscle Nerve PD JAN PY 2015 VL 51 IS 1 BP 137 EP 143 DI 10.1002/mus.24439 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AW5UY UT WOS:000346340300021 PM 25186124 ER PT J AU Chen, XP Zhao, CY Li, XL Wang, T Li, YZ Cao, C Ding, YH Dong, MQ Finci, L Wang, JH Li, XY Liu, L AF Chen, Xinping Zhao, Chunyue Li, Xiaolong Wang, Tao Li, Yizhou Cao, Cheng Ding, Yuehe Dong, Mengqiu Finci, Lorenzo Wang, Jia-huai Li, Xiaoyu Liu, Lei TI Terazosin activates Pgk1 and Hsp90 to promote stress resistance SO NATURE CHEMICAL BIOLOGY LA English DT Article ID PROGRAMMED CELL-DEATH; PHOSPHOGLYCERATE KINASE; CECAL LIGATION; SEPTIC SHOCK; SEPSIS; APOPTOSIS; GENE; INHIBITORS; MICE; MACROPHAGES AB Drugs that can protect against organ damage are urgently needed, especially for diseases such as sepsis and brain stroke. We discovered that terazosin (TZ), a widely marketed. 1-adrenergic receptor antagonist, alleviated organ damage and improved survival in rodent models of stroke and sepsis. Through combined studies of enzymology and X-ray crystallography, we discovered that TZ binds a new target, phosphoglycerate kinase 1 (Pgk1), and activates its enzymatic activity, probably through 2,4-diamino-6,7-dimethoxyisoquinoline's ability to promote ATP release from Pgk1. Mechanistically, the ATP generated from Pgk1 may enhance the chaperone activity of Hsp90, an ATPase known to associate with Pgk1. Upon activation, Hsp90 promotes multistress resistance. Our studies demonstrate that TZ has a new protein target, Pgk1, and reveal its corresponding biological effect. As a clinical drug, TZ may be quickly translated into treatments for diseases including stroke and sepsis. C1 [Chen, Xinping; Zhao, Chunyue; Wang, Tao] Peking Univ, Sch Life Sci, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China. [Chen, Xinping; Zhao, Chunyue; Wang, Tao; Liu, Lei] Capital Med Univ, Beijing Inst Brain Disorder, Beijing, Peoples R China. [Chen, Xinping; Zhao, Chunyue; Wang, Tao; Liu, Lei] Capital Med Univ, Beijing Tiantan Hosp, Beijing, Peoples R China. [Li, Xiaolong; Wang, Jia-huai] Univ Sci & Technol China, Sch Life Sci, Hefei 230026, Peoples R China. [Li, Xiaolong; Finci, Lorenzo; Wang, Jia-huai] Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China. [Li, Yizhou; Cao, Cheng; Li, Xiaoyu] Peking Univ, Coll Chem & Mol Engn, Key Lab Bioorgan Chem & Mol Engn, Beijing 100871, Peoples R China. [Ding, Yuehe; Dong, Mengqiu] Natl Inst Biol Sci, Beijing, Peoples R China. [Wang, Jia-huai] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Li, Xiaoyu] Peking Univ, Sch Chem Biol & Biotechnol, Key Lab Chem Genom, Shenzhen Grad Sch, Shenzhen, Peoples R China. RP Wang, JH (reprint author), Univ Sci & Technol China, Sch Life Sci, Hefei 230026, Peoples R China. EM jwang@red.dfci.harvard.edu; xiaoyuli@pku.edu.cn; lei_liu_2005@yahoo.com RI Wang, Tao/K-3518-2016 FU Chinese Ministry of Science and Technology [2013CB530700]; National Natural Science Foundation of China [NSFC31171324]; Beijing Institute for Brain Disorder and Beijing Tiantan Hospital, Capital Medical University, China; Ministry of Education of China; US National Institutes of Health [HL48675]; Peking-Tsinghua Center for Life Sciences FX This work was supported by the Chinese Ministry of Science and Technology (2013CB530700), the National Natural Science Foundation of China (NSFC31171324) and the Beijing Institute for Brain Disorder and Beijing Tiantan Hospital, Capital Medical University, China to L.L. and by the Ministry of Education of China and US National Institutes of Health grant HL48675 and funds from the Peking-Tsinghua Center for Life Sciences to J.W. We also acknowledge the Ministry of Science and Technology Basic Research Program (2011CB809100), the National Natural Science Foundation of China (21272016) and the Doctoral Fund of Ministry of Education of China (20120001110083) to Xiaoyu Li. We thank. L. Lai (Peking University) for her generous support in the ITC experiments. We thank the staff members at the Shanghai Synchrotron Radiation Facility and KEK-PF for generous support. NR 49 TC 9 Z9 10 U1 3 U2 33 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 EI 1552-4469 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD JAN PY 2015 VL 11 IS 1 BP 19 EP + DI 10.1038/nchembio.1657 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AW7MR UT WOS:000346448600007 PM 25383758 ER PT J AU Astarita, JL Cremasco, V Fu, JX Darnell, MC Peck, JR Nieves-Bonilla, JM Song, K Kondo, Y Woodruff, MC Gogineni, A Onder, L Ludewig, B Weimer, RM Carroll, MC Mooney, DJ Xia, LJ Turley, SJ AF Astarita, Jillian L. Cremasco, Viviana Fu, Jianxin Darnell, Max C. Peck, James R. Nieves-Bonilla, Janice M. Song, Kai Kondo, Yuji Woodruff, Matthew C. Gogineni, Alvin Onder, Lucas Ludewig, Burkhard Weimer, Robby M. Carroll, Michael C. Mooney, David J. Xia, Lijun Turley, Shannon J. TI The CLEC-2-podoplanin axis controls the contractility of fibroblastic reticular cells and lymph node microarchitecture SO NATURE IMMUNOLOGY LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; DENDRITIC CELLS; RECEPTOR CLEC-2; TUMOR INVASION; T-CELLS; PODOPLANIN; GROWTH; HOMEOSTASIS; IMMUNITY; T1-ALPHA/PODOPLANIN AB In lymph nodes, fibroblastic reticular cells (FRCs) form a collagen-based reticular network that supports migratory dendritic cells (DCs) and T cells and transports lymph. A hallmark of FRCs is their propensity to contract collagen, yet this function is poorly understood. Here we demonstrate that podoplanin (PDPN) regulates actomyosin contractility in FRCs. Under resting conditions, when FRCs are unlikely to encounter mature DCs expressing the PDPN receptor CLEC-2, PDPN endowed FRCs with contractile function and exerted tension within the reticulum. Upon inflammation, CLEC-2 on mature DCs potently attenuated PDPN-mediated contractility, which resulted in FRC relaxation and reduced tissue stiffness. Disrupting PDPN function altered the homeostasis and spacing of FRCs and T cells, which resulted in an expanded reticular network and enhanced immunity. C1 [Astarita, Jillian L.; Woodruff, Matthew C.] Harvard Univ, Sch Med, Div Med Sci, Boston, MA USA. [Astarita, Jillian L.; Cremasco, Viviana; Peck, James R.; Nieves-Bonilla, Janice M.; Turley, Shannon J.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Fu, Jianxin; Song, Kai; Kondo, Yuji; Xia, Lijun] Oklahoma Med Res Fdn, Cardiovasc Biol Res Program, Oklahoma City, OK 73104 USA. [Fu, Jianxin; Song, Kai; Kondo, Yuji; Xia, Lijun] Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73190 USA. [Darnell, Max C.; Mooney, David J.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Darnell, Max C.; Mooney, David J.] Harvard Univ, Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA. [Woodruff, Matthew C.; Carroll, Michael C.] Harvard Univ, Childrens Hosp Boston, Sch Med, Program Cellular & Mol Med, Boston, MA USA. [Gogineni, Alvin; Weimer, Robby M.] Genentech Inc, Dept Biomed Imaging, San Francisco, CA USA. [Onder, Lucas; Ludewig, Burkhard] Kantonal Hosp, Inst Immunobiol, St Gallen, Switzerland. [Turley, Shannon J.] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA USA. [Turley, Shannon J.] Genentech Inc, Dept Canc Immunol, San Francisco, CA USA. RP Turley, SJ (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM turley.shannon@gene.com FU US National Institutes of Health [R0I DK074500, P01 AI045757, R21 CA182598, 5R01 AI039246, P01 HL085607, GM103441]; American Cancer Society; Claudia Adams Barr Program in Innovative Cancer Research; Cancer Research Institute; American Heart Association [SDG7410022]; National Science Foundation FX We thank L. Cameron for assistance at the Dana-Farber Cancer Institute confocal microscopy core, and R. Gelman for help with statistical analyses. Supported by the US National Institutes of Health (R0I DK074500, P01 AI045757 and R21 CA182598 to S.J.T.; 5R01 AI039246 to M.C.C.; and P01 HL085607 and GM103441 to L.X.), the American Cancer Society (S.J.T.), the Claudia Adams Barr Program in Innovative Cancer Research (S.J.T.), the Cancer Research Institute (to V.C.), the American Heart Association (SDG7410022 to J.F.) and the National Science Foundation (J.L.A.). NR 50 TC 38 Z9 44 U1 3 U2 19 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 EI 1529-2916 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2015 VL 16 IS 1 BP 75 EP + DI 10.1038/ni.3035 PG 12 WC Immunology SC Immunology GA AW8ET UT WOS:000346494200011 PM 25347465 ER PT J AU Leavenworth, JW Verbinnen, B Yin, J Huang, HC Cantor, H AF Leavenworth, Jianmei W. Verbinnen, Bert Yin, Jie Huang, Huicong Cantor, Harvey TI A p85 alpha-osteopontin axis couples the receptor ICOS to sustained Bcl-6 expression by follicular helper and regulatory T cells SO NATURE IMMUNOLOGY LA English DT Article ID COSTIMULATOR MESSENGER-RNA; PHOSPHOINOSITIDE 3-KINASE; DENDRITIC CELLS; B-CELL; SIGNALING PATHWAYS; WIDE PREDICTION; DIFFERENTIATION; OSTEOPONTIN; MECHANISMS; INDUCTION AB Follicular helper T cells (T-FH cells) and follicular regulatory T cells (T-FR cells) regulate the quantity and quality of humoral immunity. Although both cell types express the costimulatory receptor ICOS and require the transcription factor Bcl-6 for their differentiation, the ICOS-dependent pathways that coordinate their responses are not well understood. Here we report that activation of ICOS in CD4(+) T cells promoted interaction of the p85 alpha regulatory subunit of the signaling kinase PI(3)K and intracellular osteopontin (OPN-i), followed by translocation of OPN-i to the nucleus, its interaction with Bcl-6 and protection of Bcl-6 from ubiquitin-dependent proteasome degradation. Post-translational protection of Bcl-6 by OPN-i was essential for sustained responses of T-FH cells and T-FR cells and regulation of the germinal center B cell response to antigen. Thus, the p85 alpha-OPN-i axis represents a molecular bridge that couples activation of ICOS to Bcl-6-dependent functional differentiation of T-FH cells and T-FR cells; this suggests new therapeutic avenues to manipulate the responses of these cells. C1 [Leavenworth, Jianmei W.; Verbinnen, Bert; Yin, Jie; Huang, Huicong; Cantor, Harvey] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Leavenworth, Jianmei W.; Verbinnen, Bert; Cantor, Harvey] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA USA. [Yin, Jie] Tianjin Med Univ, Sch Basic Med Sci, Dept Cell Biol, Tianjin, Peoples R China. [Huang, Huicong] Wenzhou Med Coll, Dept Parasitol, Wenzhou, Peoples R China. RP Cantor, H (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM harvey_cantor@dfci.harvard.edu FU US National Institutes of Health [AI48125, T32 CA070083]; LeRoy Schecter Research Foundation; Benacerraf Society; Belgian-American Educational Foundation FX We thank H. von Boehmer (Dana-Farber Cancer Institute) for B6.Foxp3GFP mice; L. Cantley (Weill Cornell Medical College) for p85 alpha and Flag-p85 alpha plasmids; T. Dawson (Johns Hopkins University) for the HA-Ub plasmid; S. Yamanaka (Kyoto University) for the HA-p110 delta plasmid; J. Zhao (Dana-Farber Cancer Institute) for the HA-p110 alpha plasmid; K. Wucherpfennig for critical reading; L. Cameron for help with image preparation and analysis; Y. Shao for microarray analysis; and A. Angel for preparation of the manuscript and figures. Supported by the US National Institutes of Health (AI48125 to H.C.; and T32 CA070083 to J.W.L.), The LeRoy Schecter Research Foundation (H.C.), the Benacerraf Society (J.W.L.) and the Belgian-American Educational Foundation (B.V.). NR 52 TC 22 Z9 23 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 EI 1529-2916 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2015 VL 16 IS 1 BP 96 EP + DI 10.1038/ni.3050 PG 13 WC Immunology SC Immunology GA AW8ET UT WOS:000346494200013 PM 25436971 ER PT J AU Lookabaugh, S Kelly, HR Carter, MS Niesten, MEF McKenna, MJ Curtin, H Lee, DJ AF Lookabaugh, Sarah Kelly, Hillary R. Carter, Margaret S. Niesten, Marlien E. F. McKenna, Michael J. Curtin, Hugh Lee, Daniel J. TI Radio logic Classification of Superior Canal Dehiscence: Implications for Surgical Repair SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Arcuate eminence; Geniculate ganglion; Low tegmen; Near-dehiscence; Superior canal dehiscence; Superior petrosal sinus; Tegmen defects ID PRESSURE-INDUCED VERTIGO; GENICULATE GANGLION; BONE DEHISCENCE; ROUND WINDOW; OCCLUSION; TEGMEN; PREVALENCE; MANAGEMENT; DEFECT AB Objective: Surgical access to repair a superior canal dehiscence (SCD) is influenced by the location of the bony defect and its relationship to surrounding tegmen topography as seen on computed tomography. There are currently no agreed-upon methods of characterizing these radiologic findings. We propose a formal radiologic classification system of SCD based on dehiscence location and adjacent tegmen topography. Study Design: Retrospective case review Setting: Tertiary, neurotology referral center Patients: We identified 298 patients with superior canal dehiscence on CT from February 2001 to October 2013. Of these, 251 had symptomatic superior canal dehiscence syndrome and were included in the study. Intervention: Patients underwent high-resolution temporal bone CT scans with creation of axial, coronal, Poschl, and Stenver reformatted images to examine the superior semicircular canal. Two residents-in-training and a head and neck radiologist independently read the scans. Main Outcome Measures: CT scans were assessed for (1) superior canal dehiscence or "near" dehiscence, (2) defect location relative to the skull base, (3) surrounding tegmen defects, (4) geniculate ganglion dehiscence, (5) superior petrosal sinus-associated dehiscence (SPS), (6) low-lying tegmen, and (7) the distance between the outer table of the temporal bone and the arcuate eminence. C1 [Lookabaugh, Sarah; Carter, Margaret S.; McKenna, Michael J.; Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Lookabaugh, Sarah; Carter, Margaret S.; McKenna, Michael J.; Lee, Daniel J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Kelly, Hillary R.; Curtin, Hugh] Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. [Kelly, Hillary R.; Curtin, Hugh] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Kelly, Hillary R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Niesten, Marlien E. F.] Univ Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, Utrecht, Netherlands. [Niesten, Marlien E. F.] Brain Ctr Rudolf Magnus, Utrecht, Netherlands. RP Lee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM daniel_lee@meei.harvard.edu NR 26 TC 8 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD JAN PY 2015 VL 36 IS 1 BP 118 EP 125 PG 8 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA AW6GP UT WOS:000346368200025 PM 25122602 ER PT J AU Jung, DH Lookabaugh, SA Owoc, MS McKenna, MJ Lee, DJ AF Jung, David H. Lookabaugh, Sarah A. Owoc, Maryanna S. McKenna, Michael J. Lee, Daniel J. TI Dizziness is More Prevalent than Autophony Among Patients Who Have Undergone Repair of Superior Canal Dehiscence SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Autophony; Conductive hearing loss; Dizziness; Hearing handicap; Migraine; Quality of life; Superior canal dehiscence; Vertigo ID HANDICAP INVENTORY; HEARING HANDICAP; DISABILITY; OCCLUSION; SYMPTOMS; MIGRAINE; SURGERY; QUALITY AB Objective: Studies have reported high early success rates in rectifying dizziness and autophony after primary repair of superior canal dehiscence (SCD). We sought to identify the prevalence of dizziness and autophony at later time points in patients who had undergone SCD repair. We also assessed any problems with hearing in this population, along with prevalence of headaches and decreases in overall quality of life. Study Quality Design: Identification of patients via retrospective chart review, followed by administration of multiple validated surveys. Setting: Tertiary, hospital-based neurotology practice. Patients: All 62 patients who had undergone primary SCD repair at Massachusetts Eye and Ear Infirmary with follow-up time of at least 3 months were contacted, with 38 responses from 22 women and 16 men. The average follow-up was 34 months (range, 3-155 mo). Interventions: Patient surveys. Main Outcome Measures: Dizziness Handicap Inventory and Autophony Index, Secondary Outcome Measures: Hearing Handicap Survey, MIDAS headache survey, and Short Form-36 Quality of Life Survey. Results: Twenty patients reported low DHI scores, whereas 18 patients reported elevated DIU scores corresponding to moderate-to-severe dizziness. Autophony was less prevalent, as 3 patients experienced autophony in the operated ear, whereas 3 patients experienced "unmasking" of autophony in the contralateral ear. HHI scores were not significantly different between the low DIE and high Dill group. There were significantly more female subjects in the high DHI group, which was also characterized by significantly more severe MIDAS grades and significantly worse SF-36 scores. Conclusion: Dizziness is more prevalent than autophony among patients who have undergone SCD repair, although the majority of these patients are satisfied with their decision to undergo surgery. Female sex and migraine headaches are associated with dizziness in this patient population. Further work is necessary to determine causal relationships among these associations. C1 [Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Lee, DJ (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM daniel_lee@meei.harvard.edu NR 22 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD JAN PY 2015 VL 36 IS 1 BP 126 EP 132 PG 7 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA AW6GP UT WOS:000346368200026 PM 25122596 ER PT J AU Merchant, GR Roosli, C Niesten, MEF Hamade, MA Lee, DJ McKinnon, ML Ulku, CH Rosowski, JJ Merchant, SN Nakajima, HH AF Merchant, Gabrielle R. Roeoesli, Christof Niesten, Marlien E. F. Hamade, Mohamad A. Lee, Daniel J. McKinnon, Melissa L. Ulku, Cagatay H. Rosowski, John J. Merchant, Saumil N. Nakajima, Hideko Heidi TI Power Reflectance as a Screening Tool for the Diagnosis of Superior Semicircular Canal Dehiscence SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Admittance; Energy reflectance; Power reflectance; Reflectance; Superior canal dehiscence; Superior semicircular canal dehiscence; Wideband acoustic immittance ID EVOKED MYOGENIC POTENTIALS; CONDUCTIVE HEARING-LOSS; UMBO VELOCITY; BONE; VERTIGO AB Hypothesis: Power reflectance (PR) measurements in ears with superior canal dehiscence (SCD) have a characteristic pattern, the detection of which can assist in diagnosis. Background: The aim of this study was to determine whether PR coupled with a novel detection algorithm can perform well as a fast, noninvasive, and easy screening test for SCD. The screening test aimed to determine whether patients with various vestibular and/or auditory symptom(s) should be further considered for more expensive and invasive tests that better define the diagnosis of SCD (and other third-window lesions). Methods: Power reflectance was measured in patients diagnosed with SCD by high-resolution computed tomography. The study included 40 ears from 32 patients with varying symptoms (e.g., with and without conductive hearing loss, vestibular symptoms, and abnormal auditory sensations). Results: Power reflectance results were compared to previously published norms and showed that SCD is commonly associated with a PR notch near 1 kHz. An analysis algorithm was designed to detect such notches and to quantify their incidence in affected and normal ears. Various notch detection thresholds yielded sensitivities of 80% to 93%, specificities of 69% to 72%, negative predictive values of 84% to 93%, and a positive predictive value of 67%. Conclusion: This study shows evidence that PR measurements together with the proposed notch-detecting algorithm can be used to quickly and effectively screen patients for third-window lesions such as SCD in the early stages of a diagnostic work up. C1 [Merchant, Gabrielle R.; Roeoesli, Christof; Niesten, Marlien E. F.; Hamade, Mohamad A.; Lee, Daniel J.; McKinnon, Melissa L.; Ulku, Cagatay H.; Rosowski, John J.; Merchant, Saumil N.; Nakajima, Hideko Heidi] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Merchant, Gabrielle R.; Merchant, Saumil N.; Nakajima, Hideko Heidi] Harvard MIT Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Progrcun, Cambridge, MA USA. [Roeoesli, Christof; Niesten, Marlien E. F.; Hamade, Mohamad A.; Lee, Daniel J.; Ulku, Cagatay H.; Rosowski, John J.; Merchant, Saumil N.; Nakajima, Hideko Heidi] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Roeoesli, Christof] Univ Zurich Hosp, Dept Otorhinolaryngol Head & Neck Surg, CH-8091 Zurich, Switzerland. [Niesten, Marlien E. F.] Univ Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, Utrecht, Netherlands. [Ulku, Cagatay H.] Necmettin Erbakan Univ, Meram Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Konya, Turkey. RP Nakajima, HH (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM heidi_nakajima@meei.harvard.edu FU Nachwuchsforderungskredit of the University of Zurich; TUBITAK; National Institutes of Health/National Institute on Deafness and Other Communication Disorders [R01DC004790, R03DC011158] FX This study was made possible owing to support from the Nachwuchsforderungskredit of the University of Zurich (C. R.), TUBITAK (C. H. U.), and the National Institutes of Health/National Institute on Deafness and Other Communication Disorders (R01DC004790 to S. N. M. and R03DC011158 to H. H. N.). NR 21 TC 2 Z9 2 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD JAN PY 2015 VL 36 IS 1 BP 172 EP 177 PG 6 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA AW6GP UT WOS:000346368200033 PM 25076227 ER PT J AU Delahunt, B Hammond, E Egevad, L Samaratunga, H Srigley, JR Humphrey, PA Rubin, M Epstein, JI Lin, DW Gore, JL Nacey, JN Klotz, L Sandler, H Zietman, AL Holden, S Montironi, R Evans, AJ McKenney, JK Berney, D Wheeler, TM Chinnaiyan, AM True, L Knudsen, B Amin, MB AF Delahunt, Brett Hammond, Elizabeth Egevad, Lars Samaratunga, Hemamali Srigley, John R. Humphrey, Peter A. Rubin, Mark Epstein, Jonathan I. Lin, Daniel W. Gore, John L. Nacey, John N. Klotz, Laurence Sandler, Howard Zietman, Anthony L. Holden, Stuart Montironi, Rodolfo Evans, Andrew J. McKenney, Jesse K. Berney, Dan Wheeler, Thomas M. Chinnaiyan, Arul M. True, Lawrence Knudsen, Beatrice Amin, Mahul B. TI Active surveillance for prostate cancer: the role of the pathologist SO PATHOLOGY LA English DT Editorial Material ID INTERNATIONAL-SOCIETY; UROLOGICAL-PATHOLOGY; RADICAL PROSTATECTOMY; CARCINOMA; BIOPSY; TRENDS C1 [Delahunt, Brett] Univ Otago, Wellington Sch Med & Hlth Sci, Dept Pathol & Mol Med, Wellington, New Zealand. [Hammond, Elizabeth] Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA. [Egevad, Lars] Karolinska Univ Hosp, Dept Pathol & Oncol, Solna, Sweden. [Samaratunga, Hemamali] Aquesta Pathol, Brisbane, Qld, Australia. [Samaratunga, Hemamali] Univ Queensland, Brisbane, Qld, Australia. [Srigley, John R.] Trillium Hlth Partners, Mississauga, ON, Canada. [Srigley, John R.] McMaster Univ, Hamilton, ON, Canada. [Humphrey, Peter A.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. [Rubin, Mark] NYU, Weill Med Coll Cornell, Inst Precis Med, New York, NY USA. [Rubin, Mark] NYU, Weill Med Coll Cornell, Dept Pathol & Lab Med, New York, NY USA. [Rubin, Mark] New York Presbyterian Hosp, New York, NY USA. [Epstein, Jonathan I.] Johns Hopkins Sch Med, Dept Pathol Urol & Oncol, Baltimore, MA USA. [Lin, Daniel W.; Gore, John L.] Univ Washington, Dept Urol, Seattle, WA 98195 USA. [Nacey, John N.] Univ Otago, Wellington Sch Med & Hlth Sci, Dept Surg, Wellington, New Zealand. [Klotz, Laurence] Univ Toronto, Div Urol, Toronto, ON, Canada. [Sandler, Howard] Cedars Sinai Med Ctr, Dept Radiat Oncol, Los Angeles, CA 90048 USA. [Zietman, Anthony L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Holden, Stuart] Cedars Sinai Med Ctr, Dept Urol, Los Angeles, CA 90048 USA. [Montironi, Rodolfo] Univ Marche Reg Ancona, Polytech Univ, Dept Biomed Sci & Publ Hlth, Sect Pathol Anat, Ancona, Italy. [Evans, Andrew J.] Univ Toronto, Univ Hlth Network, Toronto, ON, Canada. [McKenney, Jesse K.] Cleveland Clin Fdn, Pathol & Lab Med Inst, Cleveland, OH 44195 USA. [Berney, Dan] Royal London Hosp, Dept Cellular Pathol, London E1 1BB, England. [Wheeler, Thomas M.] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Chinnaiyan, Arul M.] Univ Michigan, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA. [True, Lawrence] Univ Washington, Med Ctr, Dept Pathol, Seattle, CA USA. [Knudsen, Beatrice] Cedars Sinai Med Ctr, Dept Biomed Sci, Los Angeles, CA 90048 USA. [Knudsen, Beatrice; Amin, Mahul B.] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA. RP Delahunt, B (reprint author), Univ Otago, Wellington Sch Med & Hlth Sci, Dept Pathol & Mol Med, Wellington, New Zealand. EM brett.delahunt@otago.ac.nz RI Samaratunga, Hemamali/D-1559-2013; OI Samaratunga, Hemamali/0000-0001-5796-1791; Rubin, Mark/0000-0002-8321-9950; Berney, Daniel/0000-0001-5474-8696 NR 15 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0031-3025 EI 1465-3931 J9 PATHOLOGY JI Pathology PD JAN PY 2015 VL 47 IS 1 BP 1 EP 3 DI 10.1097/PAT.0000000000000186 PG 3 WC Pathology SC Pathology GA AW6DG UT WOS:000346359000001 PM 25474525 ER PT J AU Ramirez, MF Tran, P Cata, JP AF Ramirez, Maria F. Tran, Peter Cata, Juan P. TI The Effect of Clinically Therapeutic Plasma Concentrations of Lidocaine on Natural Killer Cell Cytotoxicity SO REGIONAL ANESTHESIA AND PAIN MEDICINE LA English DT Article ID LOCAL-ANESTHETICS; IMMUNE FUNCTION; RECEPTOR; NKG2D; ACTIVATION; MECHANISMS; PROPOFOL; PAIN AB Background: Natural killer (NK) cells can induce death in cancer cells. Previous studies suggest that lidocaine may decrease the function of NK cells. However, it is unknown whether lower concentrations of lidocaine, usually found in patients managed with continuous infusions, also impair the function of NK cells. We hypothesized that lidocaine at low concentrations preserves the function of NK cells. Methods: Cytotoxicity assays were performed to assess the function of NK cells treated with different concentrations of lidocaine (0.01-50 mu M) against K562, THP-1, and OCI-AML(3) cells. Similar experiments were repeated with neutralizing NK group 2, member D (NKG2D) receptor antibody or granzyme B inhibitor. The concentrations of interferon-gamma, perforin, and granzyme B and the expression of NKG2D receptor ligands (major histocompatibility I complex antigen and UL16-binding protein) were measured by enzyme-linked immunosorbent assay or Western blot. Values of P < 0.05 were considered statistically significant. Results: In vitro, lidocaine enhanced the NK cell cytotoxicity against K562 at 0.01 and 0.1 mu M (P = 0.001) and against THP-1 (P = 0.0013) and OCI-AML3 (P = 0.0043) cells at all tested concentrations. This observed effect was inhibited by the addition of a granzyme B inhibitor and NKG2D receptor blocker (THP-1, P = 0.0005 and P = 0.0001; and OCI-AML3, P = 0.0862 and P = 0.0133). Lidocaine did not induce major histocompatibility I complex antigen or UL16-binding protein. Conclusions: Our findings suggest that clinically relevant concentrations of lidocaine enhance the in vitro function of NK cells via the release of lytic granules. C1 [Ramirez, Maria F.] Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02115 USA. [Tran, Peter] Univ Texas MD Anderson Canc Ctr, Dept Canc Syst Imaging, Houston, TX 77030 USA. [Cata, Juan P.] Univ Texas MD Anderson Canc Ctr, Dept Anesthesiol & Perioperat Med, Houston, TX 77030 USA. RP Cata, JP (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Anesthesiol & Perioperat Med, Fac Ctr, Floor 13,FC13-2000,1400 Holcombe Blvd,Unit 409, Houston, TX 77030 USA. EM jcata@mdanderson.org NR 21 TC 4 Z9 4 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-7339 EI 1532-8651 J9 REGION ANESTH PAIN M JI Region. Anesth. Pain Med. PD JAN-FEB PY 2015 VL 40 IS 1 BP 43 EP 48 DI 10.1097/AAP.0000000000000191 PG 6 WC Anesthesiology SC Anesthesiology GA AW7ZW UT WOS:000346481400008 PM 25469757 ER PT J AU Abi-Ghanem, AS McGrath, MA Jacene, HA AF Abi-Ghanem, Alain S. McGrath, Mary A. Jacene, Heather A. TI Radionuclide Therapy for Osseous Metastases in Prostate Cancer SO SEMINARS IN NUCLEAR MEDICINE LA English DT Review ID PAINFUL BONE METASTASES; PHASE-II TRIAL; MITOXANTRONE PLUS PREDNISONE; DOUBLE-BLIND; SKELETAL METASTASES; RADIOPHARMACEUTICAL THERAPY; RADIUM-223 CHLORIDE; INCREASED SURVIVAL; TARGETED THERAPY; EMITTING RA-223 AB Bone metastases are associated with increased morbidity and poor prognosis in castration-resistant prostate cancer. Since 2010, 5 systemic therapies for metastatic castration-resistant prostate cancer have been approved by the US Food and Drug Administration based on an improvement in overall survival, offering alternatives to docetaxel, a chemotherapeutic agent with modest effect and significant toxicity. These systemic treatments belong to different classes of medication such as immunotherapy, hormonal therapy, chemotherapy, and radionuclide therapy. Radium-223 dichloride ((RaCl2)-Ra-223), approved in May 2013, is a novel aemitting radiopharmaceutical that targets areas of increased bone turnover in bone metastases, delivering densely ionizing radiation within a short tissue range and causing more severe chromosomal damage than beta-emitting radiopharmaceuticals. In this article, we review the clinical development of (RaCl2)-Ra-223, focusing on its effects on pain relief, skeletal events, biochemical markers, overall survival, quality of life, and safety. We also outline the differences between (RaCl2)-Ra-223 and the previously developed bone-seeking beta-emitters and briefly present new trials on the horizon involving (RaCl2)-Ra-223. (C) 2015 Elsevier Inc. All rights reserved. C1 [Abi-Ghanem, Alain S.] SUNY Upstate Med Univ, Dept Radiol, Syracuse, NY 13210 USA. [McGrath, Mary A.] SUNY Upstate Med Univ, Dept Radiol, Div Nucl Med, Syracuse, NY 13210 USA. [Jacene, Heather A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Nucl Med,Dept Imaging, Boston, MA 02115 USA. RP Abi-Ghanem, AS (reprint author), SUNY Upstate Med Univ, Dept Radiol, 750E Adams St,Room 3428, Syracuse, NY 13210 USA. EM abighana@upstate.edu NR 71 TC 9 Z9 9 U1 1 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0001-2998 EI 1558-4623 J9 SEMIN NUCL MED JI Semin. Nucl. Med. PD JAN PY 2015 VL 45 IS 1 BP 66 EP 80 DI 10.1053/j.semnuclmed.2014.07.006 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AX0DK UT WOS:000346623400008 PM 25475380 ER PT J AU Hobai, IA Edgecomb, J LaBarge, K Colucci, WS AF Hobai, Ion A. Edgecomb, Jessica LaBarge, Kara Colucci, Wilson S. TI DYSREGULATION OF INTRACELLULAR CALCIUM TRANSPORTERS IN ANIMAL MODELS OF SEPSIS-INDUCED CARDIOMYOPATHY SO SHOCK LA English DT Article DE L-type Ca2+ channel; SERCA; Na+; Ca2+ exchange; ryanodine receptor; myofilaments; AP action potential; Ca2+ calcium; Ca-SR sarcoplasmic reticulum calcium load; CLP cecal ligation and puncture; Cys(674)-S0(3)H sulfonylation of cysteine 674 of SERCA; Ca-i calcium transient amplitude; ECC excitation-contraction coupling; i; p; intraperitoneally; i; v; intravenously; LPS lipopolysaccharide; LTCC L-type Ca2+ channels; PKA phosphokinase A; PLB phospholamban; RONS radical oxygen; nitrogen species; ROS radical oxygen species; RyR ryanodine receptors; SERCA sarcoplasmic reticulum calcium pump; SR sarcoplasmic reticulum; SIC sepsis-induced cardiomyopathy; TnI troponin I ID CARDIAC SARCOPLASMIC-RETICULUM; INDUCED MYOCARDIAL DYSFUNCTION; NITRIC-OXIDE SYNTHASE; ADRENOMEDULLIN BINDING PROTEIN-1; RAT VENTRICULAR MYOCYTES; ENDOTOXEMIC GUINEA-PIGS; CANINE HEART-FAILURE; SEPTIC SHOCK; CELLULAR MECHANISMS; CONTRACTILE DYSFUNCTION AB Sepsis-induced cardiomyopathy (SIC) develops as the result of myocardial calcium (Ca2+) dysregulation. Here we reviewed all published studies that quantified the dysfunction of intracellular Ca2+ transporters and the myofilaments in animal models of SIC. Cardiomyocytes isolated from septic animals showed, invariably, a decreased twitch amplitude, which is frequently caused by a decrease in the amplitude of cellular Ca2+ transients (Ca-i) and sarcoplasmic reticulum (SR) Ca2+ load (Ca-SR). Underlying these deficits, the L-type Ca2+ channel is downregulated, through mechanisms that may involve adrenomedullin-mediated redox signaling. The SR Ca2+ pump is also inhibited, through oxidative modifications (sulfonylation) of one reactive thiol group (on Cys(674)) and/or modulation of phospholamban. Diastolic Ca2+ leak of ryanodine receptors is frequently increased. In contrast, Na+/Ca2+ exchange inhibition may play a partially compensatory role by increasing Ca-SR and Ca-i. The action potential is usually shortened. Myofilaments show a bidirectional regulation, with decreased Ca2+ sensitivity in milder forms of disease (due to troponin I hyperphosphorylation) and an increase (redox mediated) in more severe forms. Most deficits occurred similarly in two different disease models, induced by either intraperitoneal administration of bacterial lipopolysaccharide or cecal ligation and puncture. In conclusion, substantial cumulative evidence implicates various Ca2+ transporters and the myofilaments in SIC pathology. What is less clear, however, are the identity and interplay of the signaling pathways that are responsible for Ca2+ transporters dysfunction. With few exceptions, all studies we found used solely male animals. Identifying sex differences in Ca2+ dysregulation in SIC becomes, therefore, another priority. C1 [Hobai, Ion A.; Edgecomb, Jessica; LaBarge, Kara; Colucci, Wilson S.] Boston Univ, Med Ctr, Dept Med, Cardiovasc Med Sect, Boston, MA 02118 USA. [Hobai, Ion A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Hobai, IA (reprint author), Boston Univ, Med Ctr, Evans Basic Res Bldg,650 Albany St,X740, Boston, MA 02118 USA. EM ihobai@partners.org FU National Institute of General Medical Sciences [K08GM096082, T32GM007592]; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts FX I.A.H. acknowledges support from K08GM096082 and T32GM007592 (National Institute of General Medical Sciences) and the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts. NR 96 TC 7 Z9 7 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1073-2322 EI 1540-0514 J9 SHOCK JI Shock PD JAN PY 2015 VL 43 IS 1 BP 3 EP 15 DI 10.1097/SHK.0000000000000261 PG 13 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA AW7CR UT WOS:000346422700002 PM 25186837 ER PT J AU Suri, P Hunter, DJ Boyko, EJ Rainville, J Guermazi, A Katz, JN AF Suri, Pradeep Hunter, David J. Boyko, Edward J. Rainville, James Guermazi, Ali Katz, Jeffrey N. TI Physical activity and associations with computed tomography-detected lumbar zygapophyseal joint osteoarthritis SO SPINE JOURNAL LA English DT Article DE Facet; Lumbar; Arthritis; Rehabilitation; Computed tomography; Exercise ID MALE MONOZYGOTIC TWINS; 5-YEAR FOLLOW-UP; DISC DEGENERATION; CARDIOVASCULAR-DISEASE; CORONARY-ARTERY; FACET JOINTS; BACK-PAIN; PROGRESSION; SPINE; DETERMINANTS AB BACKGROUND CONTEXT: There are no previous epidemiologic studies examining associations between physical activity and imaging-detected lumbar zygapophyseal joint osteoarthritis (ZJO) in a community-based sample. PURPOSE: To determine whether physical activity is associated with prevalent lumbar ZJO on computed tomography (CT). STUDY DESIGN/SETTING: A community-based cross-sectional study. PATIENT SAMPLE: Four hundred twenty-four older adults from the Framingham Heart Study. OUTCOME MEASURES: Participants received standardized CT assessments of lumbar ZJO at the L2-S1 levels. Severe lumbar ZJO was defined according to the presence and/or degree of joint space narrowing, osteophytosis, articular process hypertrophy, articular erosions, subchondral cysts, and intra-articular vacuum phenomenon. This definition of lumbar ZJO was based entirely on CT imaging findings and did not include any clinical criteria such as low back pain. METHODS: Physical activity was measured using the Physical Activity Index, which estimate hours per day typically spent in these activity categories: sleeping, sitting, slight activity, moderate activity, and heavy activity. Participants reported on usual frequency of walking, running, swimming, and weightlifting. We used multivariable logistic regression to examine associations between self-reported activity and severe lumbar ZJO, while adjusting for key covariates including age, sex, height, and weight. RESULTS: In multivariable analyses, ordinal categories of heavy physical activity duration per day were significantly associated with severe lumbar ZJO (p for trend = .04), with the greatest risk observed for the category 3 or more hours per day, odds ratio 2.13 (95% confidence interval [CI] 0.97-4.67). When heavy activity was modeled as a continuous independent variable, each hour was independently associated with 1.19 times the odds of severe lumbar ZJO (95% CI 1.03-1.38, p = .02). Less vigorous types of physical activity and the type of exercise were not associated with severe lumbar ZJO. Older age, lesser height, and greater weight were independently and significantly associated with severe lumbar ZJO. In multivariable models predicting lumbar ZJO, neither model discrimination nor reclassification improved with the addition of physical activity variables, compared with a multivariable model including age, sex, height, and weight. CONCLUSIONS: Our findings demonstrate a statistically significant cross-sectional association between heavy physical activity and CT-detected severe lumbar ZJO. However, the additional discriminatory capability of heavy physical activity above and beyond that contributed by other factors was negligible. Published by Elsevier Inc. C1 [Suri, Pradeep; Boyko, Edward J.] VA Puget Sound Healthcare Syst, Seattle, WA 98108 USA. [Suri, Pradeep] Univ Washington, Sch Med, Dept Rehabil Med, Seattle, WA 98103 USA. [Hunter, David J.] Univ Sydney, Royal N Shore Hosp, Clin Adm 7C, Dept Rheumatol,Kolling Inst, St Leonards, NSW 2065, Australia. [Boyko, Edward J.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98103 USA. [Rainville, James] New England Baptist Hosp, Boston, MA 02120 USA. [Guermazi, Ali] Boston Univ, Sch Med, Dept Radiol, Boston, MA 02215 USA. [Katz, Jeffrey N.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy,Dept Med, Boston, MA 02446 USA. [Katz, Jeffrey N.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02446 USA. RP Suri, P (reprint author), VA Puget Sound Healthcare Syst, 1660 S Columbian Way,RCS 117, Seattle, WA 98108 USA. EM pradeep.suriyaarachchi@va.gov FU Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health; Boston University School of Medicine; National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; Rehabilitation Medicine Scientist Training Program; National Institutes of Health [K12 HD 01097]; New England Baptist Hospital Research Funding Award; Elizabeth Stent Fund; National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases [P60 AR 47782]; Australian Research Council Future Fellowship; VA Puget Sound FX From the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine. The National Heart, Lung, and Blood Institute's Framingham Heart Study contract (No. N01-HC-25195) supported the recruitment, enrollment, and examination of the Offspring and Third-Generation Cohorts and the computed tomography scans. Dr PS and this research were funded by the Rehabilitation Medicine Scientist Training Program and the National Institutes of Health (K12 HD 01097), with supplemental funding from the New England Baptist Hospital Research Funding Award and the Elizabeth Stent Fund. VA Puget Sound provided support for Dr PS's participation in this research. Dr JNK was funded in part by National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases P60 AR 47782. Dr DJH was funded by an Australian Research Council Future Fellowship. VA Puget Sound provided support for Dr EJB's participation in this research. There were no study-specific conflict of interest-associated biases. NR 31 TC 1 Z9 1 U1 3 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-9430 EI 1878-1632 J9 SPINE J JI Spine Journal PD JAN PY 2015 VL 15 IS 1 BP 42 EP 49 DI 10.1016/j.spinee.2014.06.022 PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA AW6OP UT WOS:000346389000008 PM 25011094 ER PT J AU Redjal, N Zhu, Y Shah, K AF Redjal, Navid Zhu, Yanni Shah, Khalid TI Combination of Systemic Chemotherapy with Local Stem Cell Delivered S-TRAIL in Resected Brain Tumors SO STEM CELLS LA English DT Article DE GBM; Primary-human-derived GBM; Stem cell therapy; TRAIL; Cisplatin; Resection ID APOPTOSIS-INDUCING LIGAND; PHASE-II; IN-VIVO; MALIGNANT GLIOMA; SYNERGISTIC CYTOTOXICITY; GLIOBLASTOMA CELLS; 1ST-LINE TREATMENT; CANCER; TEMOZOLOMIDE; RESISTANCE AB Despite advances in standard therapies, the survival of glioblastoma multiforme (GBM) patients has not improved. Limitations to successful translation of new therapies include poor delivery of systemic therapies and use of simplified preclinical models which fail to reflect the clinical complexity of GBMs. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis specifically in tumor cells and we have tested its efficacy by on-site delivery via engineered stem cells (SC) in mouse models of GBM that mimic the clinical scenario of tumor aggressiveness and resection. However, about half of tumor lines are resistant to TRAIL and overcoming TRAIL-resistance in GBM by combining therapeutic agents that are currently in clinical trials with SC-TRAIL and understanding the molecular dynamics of these combination therapies are critical to the broad use of TRAIL as a therapeutic agent in clinics. In this study, we screened clinically relevant chemotherapeutic agents for their ability to sensitize resistant GBM cell lines to TRAIL induced apoptosis. We show that low dose cisplatin increases surface receptor expression of death receptor 4/5 post G2 cycle arrest and sensitizes GBM cells to TRAIL induced apoptosis. In vivo, using an intracranial resection model of resistant primary human-derived GBM and real-time optical imaging, we show that a low dose of cisplatin in combination with synthetic extracellular matrix encapsulated SC-TRAIL significantly decreases tumor regrowth and increases survival in mice bearing GBM. This study has the potential to help expedite effective translation of local stem cell-based delivery of TRAIL into the clinical setting to target a broad spectrum of GBMs. C1 [Redjal, Navid; Zhu, Yanni; Shah, Khalid] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurotherapy & Imaging Lab, Boston, MA 02114 USA. [Zhu, Yanni; Shah, Khalid] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Redjal, Navid] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Shah, Khalid] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Shah, Khalid] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Shah, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Dept Neurol, Boston, MA 02114 USA. EM kshah@mgh.harvard.edu FU James McDonnell Foundation; [RO1 CA138922]; [R01 CA173077] FX We would like to thank Jordi Martinez-Quintanilla, Daniel Stuckey, and Deepak Bhere for their technical assistance. This work was supported by RO1 CA138922 (K.S.), R01 CA173077 (K.S.), and James McDonnell Foundation (K.S.). NR 44 TC 3 Z9 4 U1 1 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 EI 1549-4918 J9 STEM CELLS JI Stem Cells PD JAN PY 2015 VL 33 IS 1 BP 101 EP 110 DI 10.1002/stem.1834 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA AW8ES UT WOS:000346494100011 PM 25186100 ER PT J AU Teo, GSL Yang, ZJ Carman, CV Karp, JM Lin, CP AF Teo, Grace Sock Leng Yang, Zijiang Carman, Christopher V. Karp, Jeffrey M. Lin, Charles P. TI Intravital Imaging of Mesenchymal Stem Cell Trafficking and Association With Platelets and Neutrophils SO STEM CELLS LA English DT Article DE Mesenchymal stem cells; Trafficking; Inflammation; Platelets; Neutrophils; Intravital imaging ID VASCULAR-PERMEABILITY; EXTRACELLULAR TRAPS; ENDOTHELIAL-CELLS; TARGETED-DELIVERY; STROMAL CELLS; BONE-MARROW; IN-VITRO; LEUKOCYTE EXTRAVASATION; TUMOR-CELLS; LYMPH-NODES AB Early events of mesenchymal stem/stromal cell (MSC) adhesion to and transmigration through the vascular wall following systemic infusion are important for MSC trafficking to inflamed sites, yet are poorly characterized in vivo. Here, we used intravital confocal imaging to determine the acute extravasation kinetics and distribution of culture-expanded MSC (2-6 hours postinfusion) in a murine model of dermal inflammation. By 2 hours postinfusion, among the MSC that arrested within the inflamed ear dermis, 47.8% +/- 8.2% of MSC had either initiated or completed transmigration into the extravascular space. Arrested and transmigrating MSCs were equally distributed within both small capillaries and larger venules. This suggested existence of an active adhesion mechanism, since venule diameters were greater than those of the MSC. Heterotypic intravascular interactions between distinct blood cell types have been reported to facilitate the arrest and extravasation of leukocytes and circulating tumor cells. We found that 42.8% +/- 24.8% of intravascular MSC were in contact with neutrophil-platelet clusters. A role for platelets in MSC trafficking was confirmed by platelet depletion, which significantly reduced the preferential homing of MSC to the inflamed ear, although the total percentage of MSC in contact with neutrophils was maintained. Interestingly, although platelet depletion increased vascular permeability in the inflamed ear, there was decreased MSC accumulation. This suggests that increased vascular permeability is unnecessary for MSC trafficking to inflamed sites. These findings represent the first glimpse into MSC extravasation kinetics and microvascular distribution in vivo, and further clarify the roles of active adhesion, the intravascular cellular environment, and vascular permeability in MSC trafficking. C1 [Teo, Grace Sock Leng; Yang, Zijiang; Karp, Jeffrey M.] Harvard MIT Hlth Sci & Technol, Cambridge, MA USA. [Teo, Grace Sock Leng; Yang, Zijiang; Carman, Christopher V.; Karp, Jeffrey M.; Lin, Charles P.] Harvard Univ, Sch Med, Boston, MA USA. [Teo, Grace Sock Leng; Carman, Christopher V.] Beth Israel Deaconess Med Ctr, Ctr Vasc Biol, Boston, MA 02215 USA. [Teo, Grace Sock Leng; Yang, Zijiang; Karp, Jeffrey M.] Brigham & Womens Hosp, Dept Biomed Engn, Harvard Stem Cell Inst, Cambridge, MA USA. [Teo, Grace Sock Leng; Yang, Zijiang; Lin, Charles P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Yang, Zijiang] Shanghai Jiao Tong Univ, Adv Ind Technol Res Inst, Shanghai 200030, Peoples R China. RP Karp, JM (reprint author), 65 Landsdowne St, Cambridge, MA 02139 USA. EM jeffkarp.bwh@gmail.com; charles_lin@hms.harvard.edu RI Carman, Christopher/L-8108-2016 OI Carman, Christopher/0000-0001-7358-2548 FU NCRR of the NIH [P40RR017447]; National Institutes of Health (NIH) [HL104006]; NIH [HL095722, R01 EB017274, U01 HL100402, P41 EB015903-02S1]; Department of Defense [W81XWH-13-1-0305] FX Some of the materials used in this work were provided by the Texas A&M Health Science Center College of Medicine Institute for Regenerative Medicine at Scott & White through a grant from NCRR of the NIH, Grant no. P40RR017447. This work was also funded in part by the National Institutes of Health (NIH) R01 Grant HL104006 to C. V. C., the NIH Grant HL095722 to J. M. K., a Department of Defense Grant no. W81XWH-13-1-0305 to J. M. K., the Movember Prostate Cancer Foundation Challenge Award to J. M. K., and NIH Grants R01 EB017274, U01 HL100402, and P41 EB015903-02S1 to C. P. L. The authors would like to thank Luke Mortensen and Clemens Alt for their assistance with in vivo confocal microscopy and helpful discussions. Also, we thank Roberta Martinelli for helpful discussions about NETs, and Rens Zonnefeld, Traci Anderson, and Dylan Dupuis for their assistance with in vitro NET assays. Finally, we are grateful to Priya Misir and Caroline Chen for their help with image analysis. NR 70 TC 12 Z9 12 U1 2 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 EI 1549-4918 J9 STEM CELLS JI Stem Cells PD JAN PY 2015 VL 33 IS 1 BP 265 EP 277 DI 10.1002/stem.1848 PG 13 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA AW8ES UT WOS:000346494100025 PM 25263183 ER PT J AU Kaafarani, HMA Velmahos, GC AF Kaafarani, Haytham M. A. Velmahos, George C. TI Intraoperative adverse events: The neglected quality indicator of surgical care? SO SURGERY LA English DT Editorial Material ID IMPROVEMENT PROGRAM; MORTALITY CONFERENCE; AMERICAN-COLLEGE; PATIENT SAFETY; COMPLICATIONS; CLASSIFICATION; SURGERY; MORBIDITY C1 [Kaafarani, Haytham M. A.; Velmahos, George C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Kaafarani, HMA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hkaafarani@mgh.harvard.edu NR 13 TC 1 Z9 1 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD JAN PY 2015 VL 157 IS 1 BP 6 EP 7 DI 10.1016/j.surg.2014.10.001 PG 2 WC Surgery SC Surgery GA AX0BY UT WOS:000346619700002 PM 25482460 ER PT J AU Ray, LA Courtney, KE Ghahremani, DG Miotto, K Brody, A London, ED AF Ray, Lara A. Courtney, Kelly E. Ghahremani, Dara G. Miotto, Karen Brody, Arthur London, Edythe D. TI Varenicline, naltrexone, and their combination for heavy-drinking smokers: preliminary neuroimaging findings SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE Craving; fMRI; heavy drinker; naltrexone; smoker; varenicline ID RECEPTOR PARTIAL AGONIST; RANDOMIZED CONTROLLED-TRIAL; NICOTINE REPLACEMENT THERAPY; SMOKING-CESSATION TREATMENT; SUSTAINED-RELEASE BUPROPION; WEIGHT-GAIN; ALCOHOL DEPENDENCE; CUE REACTIVITY; BRAIN ACTIVITY; EFFICACY AB Rationale: Heavy drinking smokers constitute a sizeable and hard-to-treat subgroup of smokers, for whom tailored smoking cessation therapies are not yet available. Objective: The present study used a double-blind, randomized, 2 x 2 medication design, testing varenicline alone (VAR; 1 mg twice daily), naltrexone alone (NTX; 25mg once daily), varenicline plus naltrexone, and placebo for effects on neural activation to cigarette cues in a sample (n = 40) of heavy drinking daily smokers (>= 10 cigarettes/day). Methods: All participants were tested after a 10-12-day titration period designed to reach steady state on the target medication. Participants underwent functional neuroimaging (fMRI) for examination of brain responses to visual smoking-related (vs. neutral) cues. Results: Region of interest (ROI) analyses of brain responses to Cigarette vs. Neutral Cues indicated that the combination of VAR + NTX was associated with reduced activation of the bilateral anterior cingulate cortex as compared to placebo and to NTX alone. Exploratory whole-brain analyses also indicated significant differences in brain activation during cigarette cues in the active medications versus placebo condition. All medications suppressed left nucleus accumbens activation relative to placebo, suggesting the possibility that both medications, either alone or in combination, reduce neural signals associated with appetitive behavior. Conclusions: Although preliminary, these neuroimaging findings indicate that clinical studies of the combination of VAR + NTX for heavy drinkers trying to quit smoking may be warranted. C1 [Ray, Lara A.; Courtney, Kelly E.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Ray, Lara A.; Ghahremani, Dara G.; Miotto, Karen; Brody, Arthur; London, Edythe D.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Brody, Arthur] Univ Calif Los Angeles, VA Greater Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [London, Edythe D.] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. RP Ray, LA (reprint author), Univ Calif Los Angeles, Dept Psychol, 1285 Franz Hall,Box 951563, Los Angeles, CA 90095 USA. EM lararay@psych.ucla.edu RI Courtney, Kelly/L-6041-2016 OI Courtney, Kelly/0000-0002-9280-2435 FU California Tobacco Related Disease Research Program (TRDRP) [18KT-0020]; National Institute on Drug Abuse [DA030898]; UCLA Clinical and Translational Science Institute (CTSI) [UL1RR033176, UL1TR000124]; UCLA Training Program in Translational Neuroscience of Drug Abuse [T32 DA024635]; GSK FX This research was supported grants from the California Tobacco Related Disease Research Program (TRDRP 18KT-0020) and from the National Institute on Drug Abuse (DA030898) to LAR. Support for this study was also provided by a grant from the UCLA Clinical and Translational Science Institute (CTSI), grants UL1RR033176 and UL1TR000124. KEC was supported by the UCLA Training Program in Translational Neuroscience of Drug Abuse (T32 DA024635). LAR is a paid consultant for GSK. NR 64 TC 6 Z9 6 U1 0 U2 9 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0095-2990 EI 1097-9891 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PD JAN PY 2015 VL 41 IS 1 BP 35 EP 44 DI 10.3109/00952990.2014.927881 PG 10 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA AW1TQ UT WOS:000346073600005 PM 24949564 ER PT J AU McKinley, SK Petrusa, ER Dijk, CFV Mullen, JT Smink, DS Scott-Vernaglia, SE Kent, TS Black-Schaffer, WS Phitayakorn, R AF McKinley, Sophia K. Petrusa, Emil R. Dijk, Carina Fiedeldey-Van Mullen, John T. Smink, Douglas S. Scott-Vernaglia, Shannon E. Kent, Tara S. Black-Schaffer, W. Stephen Phitayakorn, Roy TI A multi-institutional study of the emotional intelligence of resident physicians SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Emotional intelligence; Surgical education; ACGME core competencies; Surgical residency; Graduate medical education ID MEDICAL-EDUCATION; QUESTIONNAIRE; PERFORMANCE; COMPETENCES; SELECTION; CORRELATE; VALIDITY AB BACKGROUND: Although emotional intelligence (EI) may have a role in the development of Accreditation Council for Graduate Medical Education core competencies, few studies have measured resident EI across specialties. This study aimed to describe the EI of resident physicians across multiple specialties. METHODS: Three hundred twenty five surgery, pediatric, and pathology residents at 3 large academic institutions were invited to complete the psychometrically validated Trait Emotional Intelligence Questionnaire. RESULTS: The response rate was 42.8% (n = 139). Global EI of all residents (101.0 +/- 8.1) was comparable with, but less variable than, the general population sample and was not statistically different between specialties. Compared with the norm sample, residents in the 3 specialty groups demonstrated unique combinations of areas of relative high and low development. CONCLUSIONS: There exist distinct strengths and opportunities for the development for surgery, pediatrics, and pathology residents. Future investigations could use EI profiling to create educational interventions to develop specific areas of EI and assess correlation with resident performance. (C) 2015 Elsevier Inc. All rights reserved. C1 [McKinley, Sophia K.; Petrusa, Emil R.; Mullen, John T.; Phitayakorn, Roy] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Dijk, Carina Fiedeldey-Van] EPsy Consultancy, Toronto, ON, Canada. [Smink, Douglas S.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Scott-Vernaglia, Shannon E.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Kent, Tara S.] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. [Black-Schaffer, W. Stephen] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP McKinley, SK (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. EM skmckinley@gmail.com OI Phitayakorn, Roy/0000-0002-8327-1484 NR 36 TC 6 Z9 6 U1 1 U2 12 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 2015 VL 209 IS 1 BP 26 EP 33 DI 10.1016/j.amjsurg.2014.09.015 PG 8 WC Surgery SC Surgery GA AW2MB UT WOS:000346121100005 PM 25454957 ER PT J AU Stefanidis, D Cochran, A Sevdalis, N Mellinger, J Phitayakorn, R Sullivan, M Barney, L AF Stefanidis, Dimitrios Cochran, Amalia Sevdalis, Nick Mellinger, John Phitayakorn, Roy Sullivan, Maura Barney, Linda CA Multiinst Educ Res Grp Assoc Surgi TI Research priorities for multi-institutional collaborative research in surgical education SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Delphi process; Surgical education; Multi-institutional collaborative research; Educational research; Research agenda; Association for surgical education ID MEDICAL-EDUCATION AB BACKGROUND: Research in surgical education has seen unprecedented growth but originates from single institutions and remains uncoordinated; this study aimed to generate a list of research priorities in surgical educational topics. METHODS: The membership of the Association for Surgical Education was asked to submit up to 5 research questions concerned with multi-institutional collaborative surgical education research and to identify challenges faced by surgical education researchers. A modified Delphi methodology was used to create the research agenda based on these responses. RESULTS: Surgical educators responded to 3 survey rounds. Categories of submitted questions included teaching methods and curriculum development; assessment and competency; simulation; medical student preparation and selection; impact of work hour restrictions; and faculty development. Participants cited institutional culture and practice variability and lack of institutional review board coordination as common barriers to collaborative research, while identifying extensive planning, frequent communication, and availability of dedicated research coordinators as the most important facilitators. CONCLUSIONS: Using a Delphi methodology, a prioritized agenda for multi-institutional surgical education research was developed that may help advance surgeon education. (C) 2015 Elsevier Inc. All rights reserved. C1 [Stefanidis, Dimitrios] Carolinas Healthcare Syst, Dept Surg, Charlotte, NC 28204 USA. [Cochran, Amalia] Univ Utah, Dept Surg, Salt Lake City, UT USA. [Sevdalis, Nick] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, London, England. [Mellinger, John] So Illinois Univ, Dept Surg, Springfield, IL USA. [Phitayakorn, Roy] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Sullivan, Maura] Univ So Calif, Dept Surg, Los Angeles, CA USA. [Barney, Linda] Wright State Univ, Dept Surg, Toledo, OH USA. RP Stefanidis, D (reprint author), Carolinas Healthcare Syst, Dept Surg, 1025 Morehead Med Dr, Charlotte, NC 28204 USA. EM dimitrios.stefanidis@carolinas.org OI Sevdalis, Nick/0000-0001-7560-8924; Phitayakorn, Roy/0000-0002-8327-1484 FU UK's National Institute for Health Research FX Dr Sevdalis is affiliated with the Imperial Patient Safety Translational Research Center (www.cpssq.org), which is funded by the UK's National Institute for Health Research. NR 15 TC 3 Z9 3 U1 0 U2 3 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 2015 VL 209 IS 1 BP 52 EP 58 DI 10.1016/j.amjsurg.2014.08.032 PG 7 WC Surgery SC Surgery GA AW2MB UT WOS:000346121100009 PM 25454954 ER PT J AU Glass, NE Kulaylat, AN Zheng, FB Glarner, CE Economopoulos, KP Hamed, OH Bittner, JG Sakran, JV Winfield, RD AF Glass, Nina E. Kulaylat, Afif N. Zheng, Feibi Glarner, Carly E. Economopoulos, Konstantinos P. Hamed, Osama H. Bittner, James G. Sakran, Joseph V. Winfield, Robert D. TI A national survey of educational resources utilized by the Resident and Associate Society of the American College of Surgeons membership SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Surgical education; Surgical residency training; Graduate medical education; Simulation; Barriers; SCORE ID VIRTUAL-REALITY SIMULATION; OPERATING-ROOM; SURGICAL EDUCATION; SKILLS CURRICULUM; PERFORMANCE; STUDENTS; PROGRAM AB BACKGROUND: Contemporary surgical education includes online resources, mobile platform applications, and simulation training. The aim of this study was to characterize educational tools used by surgical residents. METHODS: An anonymous web-based survey was distributed to 9,913 members of the Resident and Associate Society of the American College of Surgeons. RESULTS: We received 773 completed surveys. To prepare for examinations and expand fund of knowledge, most respondents used printed textbooks, online textbooks, and Surgical Council on Resident Education modules, respectively. Respondents used online textbooks and journal articles most often to investigate timely patient care issues. In contrast, mobile platform applications and online videos/lectures were used least. Fewer than half of respondents used simulators, limited by clinical duties, absence of feedback/supervision, and lack of working supplies. CONCLUSIONS: Traditional educational resources dominate trainee preferences, although utilization of the Surgical Council on Resident Education curriculum continues to grow. Simulators remain a required tool for laparoscopic training, and incorporation of structured feedback and improved supervision may improve utilization. (C) 2015 Elsevier Inc. All rights reserved. C1 [Glass, Nina E.] NYU, Dept Surg, Langone Med Ctr, New York, NY 10016 USA. [Kulaylat, Afif N.] Penn State Hershey Med Ctr, Dept Surg, Hershey, PA USA. [Zheng, Feibi] Houston Methodist Hosp, Dept Surg, Houston, TX USA. [Glarner, Carly E.] Univ Wisconsin, Dept Surg, Madison, WI USA. [Economopoulos, Konstantinos P.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Hamed, Osama H.] King Hussein Canc Ctr, Dept Surg, Amman, Jordan. [Bittner, James G.] Virginia Commonwealth Univ, Dept Surg, Div Bariatr & Gastrointestinal Surg, Richmond, VA USA. [Sakran, Joseph V.] Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA. [Winfield, Robert D.] Washington Univ, Dept Surg, St Louis, MO USA. RP Glass, NE (reprint author), NYU, Dept Surg, Langone Med Ctr, New York, NY 10016 USA. EM Nina.Glass.MD@gmail.com OI Economopoulos, Konstantinos/0000-0003-4856-0405; Glass, Nina/0000-0002-6821-4289; Kulaylat, Afif/0000-0001-6334-1791 NR 29 TC 7 Z9 7 U1 2 U2 5 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 2015 VL 209 IS 1 BP 59 EP 64 DI 10.1016/j.amjsurg.2014.09.016 PG 6 WC Surgery SC Surgery GA AW2MB UT WOS:000346121100010 PM 25454958 ER PT J AU Phitayakorn, R Minehart, RD Hemingway, MW Pian-Smith, MCM Petrusa, E AF Phitayakorn, Roy Minehart, Rebecca D. Hemingway, Maureen W. Pian-Smith, May C. M. Petrusa, Emil TI Relationship between physiologic and psychological measures of autonomic activation in operating room teams during a simulated airway emergency SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Galvanic skin response; Transprofessional/transdisciplinary operating room simulations; Nontechnical operating room performance; Operating room teamwork assessment tools; State-Trait Anxiety Inventory ID STRESS AB BACKGROUND: Emotional stability is important for individual and team performance during operating room (OR) emergencies. We compared physiologic and psychological anxiety assessments in OR teams during simulated events. METHODS: Twenty-two teams participated in a "cannot intubate/cannot ventilate'' simulation. Participants completed the State-Trait Anxiety Inventory and wore a galvanic skin response (GSR) sensor. Differences in State-Trait Anxiety Inventory scores and GSR levels were analyzed. Anxiety scores were correlated with GSR levels. RESULTS: Resident physicians had significantly higher trait anxiety than the nurses, certified registered nurse anesthetists, and surgical technicians (43.9 +/- 9.9 vs 38.3 +/- 9.3, P < .01). Senior practitioners had significantly higher trait anxiety than junior practitioners (43.7 +/- 9.6 vs 40.0 +/- 9.9, P = .03). All groups showed significant increases in GSR. Psychological and physiologic data did not correlate. CONCLUSIONS: Senior practitioners and residents have higher levels of baseline trait anxiety for unclear reasons. Also, OR team training results in physiological signs of anxiety that do not correlate to self-reported psychological measurements. (C) 2015 Elsevier Inc. All rights reserved. C1 [Phitayakorn, Roy; Petrusa, Emil] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02163 USA. [Phitayakorn, Roy; Minehart, Rebecca D.; Hemingway, Maureen W.; Pian-Smith, May C. M.; Petrusa, Emil] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH Learning Lab, Boston, MA USA. [Minehart, Rebecca D.; Pian-Smith, May C. M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Hemingway, Maureen W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Perioperat Serv, Boston, MA USA. RP Phitayakorn, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, 460 Wang ACC,15 Parkman St, Boston, MA 02163 USA. EM rphitayakorn@mgh.harvard.edu OI Phitayakorn, Roy/0000-0002-8327-1484 NR 12 TC 1 Z9 1 U1 3 U2 14 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 2015 VL 209 IS 1 BP 86 EP 92 DI 10.1016/j.amjsurg.2014.08.036 PG 7 WC Surgery SC Surgery GA AW2MB UT WOS:000346121100014 PM 25454964 ER PT J AU Phitayakorn, R Nick, MW Alseidi, A Lind, DS Sudan, R Isenberg, G Capella, J Hopkins, MA Petrusa, ER AF Phitayakorn, Roy Nick, Michael W. Alseidi, Adnan Lind, David Scott Sudan, Ranjan Isenberg, Gerald Capella, Jeannette Hopkins, Mary A. Petrusa, Emil R. TI WISE-MD usage among millennial medical students SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Multimedia learning; Millennial learners; WISE-MD; Internet-based learning ID EDUCATION; PERFORMANCE; TRIAL AB BACKGROUND: E-learning is increasingly common in undergraduate medical education. Internet-based multimedia materials should be designed with millennial learner utilization preferences in mind for maximal impact. METHODS: Medical students used all 20 Web Initiative for Surgical Education of Medical Doctors modules from July 1, 2013 to October 1, 2013. Data were analyzed for topic frequency, time and week day, and access to questions. RESULTS: Three thousand five hundred eighty-seven students completed 35,848 modules. Students accessed modules for average of 51 minutes. Most frequent use occurred on Sunday (23.1%), Saturday (15.4%), and Monday (14.3%). Friday had the least use (8.2%). A predominance of students accessed the modules between 7 and 10 PM (34.4%). About 80.4% of students accessed questions for at least one module. They completed an average of 40 +/- 30 of the questions. Only 827 students (2.3%) repeated the questions. CONCLUSIONS: Web Initiative for Surgical Education of Medical Doctors has peak usage during the weekend and evenings. Most frequently used modules reflect core surgical problems. Multiple factors influence the manner module questions are accessed. (C) 2015 Elsevier Inc. All rights reserved. C1 [Phitayakorn, Roy; Petrusa, Emil R.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Nick, Michael W.; Hopkins, Mary A.] NYU, Langone Med Ctr, New York, NY USA. [Alseidi, Adnan] Virginia Mason Med Ctr, Seattle, WA 98101 USA. [Lind, David Scott] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. [Sudan, Ranjan] Duke Univ, Sch Med, Durham, NC USA. [Isenberg, Gerald] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. [Capella, Jeannette] UPMC Altoona, Altoona, PA USA. RP Phitayakorn, R (reprint author), Massachusetts Gen Hosp, Dept Surg, 460 Wang ACC,15 Parkman St, Boston, MA 02114 USA. EM rphitayakorn@mgh.harvard.edu OI hopkins, mary ann/0000-0001-5037-0315; Phitayakorn, Roy/0000-0002-8327-1484 NR 23 TC 7 Z9 7 U1 0 U2 1 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 2015 VL 209 IS 1 BP 152 EP 157 DI 10.1016/j.amjsurg.2014.10.004 PG 6 WC Surgery SC Surgery GA AW2MB UT WOS:000346121100024 PM 25467305 ER PT J AU Toto, PE Skidmore, ER Terhorst, L Rosen, J Weiner, DK AF Toto, Pamela E. Skidmore, Elizabeth R. Terhorst, Lauren Rosen, Jules Weiner, Debra K. TI Goal Attainment Scaling (GAS) in geriatric primary care: A feasibility study SO ARCHIVES OF GERONTOLOGY AND GERIATRICS LA English DT Article DE GAS; Older adults; Primary care; Chronic conditions; Patient-centered care ID MONTREAL COGNITIVE ASSESSMENT; RANDOMIZED CONTROLLED-TRIAL; DECISION-MAKING; OLDER-ADULTS; CLINICAL UTILITY; OUTCOME MEASURE; MANAGEMENT; PARTICIPATE; PREFERENCES; PREVALENCE AB Objective: Evaluate the feasibility of generating patient-centered goals using GAS with older adults who have multiple chronic conditions, recruited through primary care. Method: Adults age 65+ (N = 27) were recruited from a geriatric primary care center. Participants were asked to identify 2-4 activity-based goals and set attainment levels using GAS. At 8 weeks, participants were asked to rate current level of their goal performance. Physician surveys were used to evaluate if goals were realistic and feasible, and patient surveys were implemented to evaluate satisfaction. GAS T-scores were used to quantify change in goal achievement. Results: Ninety-three percent (n = 25) of participants were able to establish a minimum of two goals using GAS. 100% of participants were able to rate goal performance at follow-up. Physician survey results identified 100% of goals realistic and 93% achievable and 100% of participants were either neutral or satisfied with the process. Significant improvement was reported in GAS change scores (t(24) = 6.54, p < 0.001). Conclusion: Findings support the feasibility of GAS for older adults with multiple chronic conditions in geriatric primary care as a strategy to facilitate patient-centered care and suggest that the process of personalized goal-setting itself may facilitate goal attainment. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Toto, Pamela E.; Skidmore, Elizabeth R.; Terhorst, Lauren] Univ Pittsburgh, Dept Occupat Therapy, Pittsburgh, PA 15260 USA. [Rosen, Jules] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Weiner, Debra K.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15261 USA. [Weiner, Debra K.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Weiner, Debra K.] Univ Pittsburgh, Clin & Translat Sci Inst, Pittsburgh, PA 15260 USA. RP Toto, PE (reprint author), Univ Pittsburgh, Dept Occupat Therapy, 5038 Forbes Tower, Pittsburgh, PA 15260 USA. EM pet3@pitt.edu FU Aging Institute of UPMC Senior Services; University of Pittsburgh FX This work was supported by a pilot seed grant from the Aging Institute of UPMC Senior Services and the University of Pittsburgh. NR 39 TC 3 Z9 3 U1 3 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-4943 EI 1872-6976 J9 ARCH GERONTOL GERIAT JI Arch. Gerontol. Geriatr. PD JAN-FEB PY 2015 VL 60 IS 1 BP 16 EP 21 DI 10.1016/j.archger.2014.10.022 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA AW1TH UT WOS:000346072400003 PM 25465505 ER PT J AU Moser, RS Schatz, P Glenn, M Kollias, KE Iverson, GL AF Moser, Rosemarie Scolaro Schatz, Philip Glenn, Megan Kollias, Kelly E. Iverson, Grant L. TI Examining prescribed rest as treatment for adolescents who are slow to recover from concussion SO BRAIN INJURY LA English DT Article DE Concussion; baseline testing; comprehensive rest; concussion management ID TRAUMATIC BRAIN-INJURY; NEUROCOGNITIVE PERFORMANCE; INTERNATIONAL-CONFERENCE; CONSENSUS STATEMENT; INTERPRETING CHANGE; VOLUNTARY EXERCISE; FOOTBALL PLAYERS; CLINICAL-SAMPLES; TEMPORAL WINDOW; UP-REGULATION AB Objective: Rest is a widely recommended treatment for concussion, but its utility is unclear following the acute stage of recovery. This study examined the effects of 1-week of prescribed rest in concussed adolescent athletes. Method: Participants were 13 adolescent athletes with persistent symptoms following a concussion. More than three-quarters (77%) had self-reported ADHD, learning disability or two prior concussions. All completed ImPACT (R) at another facility, but none completed a period of comprehensive rest prior to examination at a specialty practice. Three time points of test data were compared, to control for possible spontaneous recovery: Test 1 (external facility), Test 2 (before prescribed rest) and Test 3 (following prescribed rest). Results: Repeated measures ANOVAs revealed a significant effect of prescribed rest on all ImPACT (R) composite scores and the total symptom score. Post-hoc analyses revealed no significant differences between Time 1 and Time 2, whereas significant differences were present after prescribed rest. Following prescribed rest, having two or more reliably improved cognitive test scores or having improved symptoms was present in eight of the 13 patients (61.5%). Conclusions: A substantial percentage of adolescents with persistent symptoms following concussion showed improvement in symptoms and cognitive functioning following education, reassurance and 1-week of prescribed rest. C1 [Moser, Rosemarie Scolaro; Glenn, Megan; Kollias, Kelly E.] RSM Psychol Ctr LLC, Sports Concuss Ctr New Jersey, Lawrenceville, NJ USA. [Schatz, Philip] St Josephs Univ, Philadelphia, PA 19131 USA. [Iverson, Grant L.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Iverson, Grant L.] Spaulding Rehabil Hosp, Boston, MA USA. [Iverson, Grant L.] Massachusetts Gen Hosp, Sport Concuss Clin, Boston, MA 02114 USA. [Iverson, Grant L.] Red Sox Fdn, Boston, MA USA. [Iverson, Grant L.] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. RP Moser, RS (reprint author), Sports Concuss Ctr NJ, 3131 Princeton Pike,Bldg 5 Ste 110, Lawrenceville, NJ 08648 USA. EM rmoser@sportsconcussionnj.com RI Meijer, Anna/K-5118-2016 FU ImPACT Applications, Inc.; CNS Vital Signs; Psychological Assessment Resources (PAR, Inc.) FX Data were collected at the Sports Concussion Center of New Jersey (SCCNJ). Dr Rosemarie Moser is the owner of SCCNJ and some of the authors are employees or consultants at the Center. There were no other study sponsors. In the past, Dr Moser has served as a consultant to the International Brain Research Foundation, ImPACT Applications, Inc. and Pearson. These organizations had no role in the conceptualization or content of the current manuscript or the decision to submit for publication. In addition, she receives royalties from a book on youth concussion and special journal issue on mild traumatic brain injury. Philip Schatz, PhD, is a consultant to the Sports Concussion Center of New Jersey. He has also served as a consultant to the International Brain Research Foundation and to ImPACT Applications, Inc. to study the effects of concussion in high school and collegiate athletes. However, the latter two entities had no role in the conceptualization or content of the current manuscript or the decision to submit for publication. Grant Iverson, PhD has been reimbursed by the government, professional scientific bodies and commercial organizations for discussing or presenting research relating to mild TBI and sport-related concussion at meetings, scientific conferences and symposiums. He has a clinical and consulting practice in forensic neuropsychology involving individuals who have sustained mild TBIs (including professional athletes). He has received research funding from several test publishing companies, including ImPACT Applications, Inc., CNS Vital Signs and Psychological Assessment Resources (PAR, Inc.). He has not received research support from ImPACT Applications, Inc. in the past 3 years. He receives royalties from two books relating to neuropsychology and one test (WCST-64). NR 37 TC 7 Z9 7 U1 3 U2 15 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0269-9052 EI 1362-301X J9 BRAIN INJURY JI Brain Inj. PY 2015 VL 29 IS 1 BP 58 EP 63 DI 10.3109/02699052.2014.964771 PG 6 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA AW1WC UT WOS:000346078000008 PM 25279423 ER PT J AU Karol, SE Coustan-Smith, E Cao, XY Shurtleff, SA Raimondi, SC Choi, JK Ribeiro, RC Dahl, GV Bowman, WP Taub, JW Degar, B Leung, W Downing, JR Pui, CH Rubnitz, JE Campana, D Inaba, H AF Karol, Seth E. Coustan-Smith, Elaine Cao, Xueyuan Shurtleff, Sheila A. Raimondi, Susana C. Choi, John K. Ribeiro, Raul C. Dahl, Gary V. Bowman, William Paul Taub, Jeffrey W. Degar, Barbara Leung, Wing Downing, James R. Pui, Ching-Hon Rubnitz, Jeffrey E. Campana, Dario Inaba, Hiroto TI Prognostic factors in children with acute myeloid leukaemia and excellent response to remission induction therapy SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE acute myeloid leukaemia; minimal residual disease; paediatric; prognostic factor ID MINIMAL RESIDUAL DISEASE; ACUTE MEGAKARYOBLASTIC LEUKEMIA; STEM-CELL TRANSPLANTATION; AML02 MULTICENTER TRIAL; ONCOLOGY-GROUP; CLINICAL-SIGNIFICANCE; RANDOMIZED-TRIAL; FLOW-CYTOMETRY; RISK; RELAPSE AB Minimal residual disease (MRD) is a strong prognostic factor in children and adolescents with acute myeloid leukaemia (AML) but nearly one-quarter of patients who achieve MRD-negative status still relapse. The adverse prognostic factors among MRD-negative patients remain unknown. We analysed the AML02 study cohort to identify demographic and genetic prognostic factors. Among the presenting features, certain 11q23 abnormalities, such as t(6;11) and t(10;11), acute megakaryoblastic leukaemia without the t(1;22), and age 10years were associated with inferior outcome in patients who had MRD-negative status after either remission induction I or II. By contrast, those with rearrangement of CBF genes had superior outcome. Our study identifies patient populations for whom close post-remission MRD monitoring to detect and treat emerging relapse and adjustment in treatment intensity might be indicated. C1 [Karol, Seth E.; Ribeiro, Raul C.; Pui, Ching-Hon; Rubnitz, Jeffrey E.; Inaba, Hiroto] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA. [Coustan-Smith, Elaine; Campana, Dario] Natl Univ Singapore, Dept Paediat, Singapore 117548, Singapore. [Cao, Xueyuan] St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38105 USA. [Shurtleff, Sheila A.; Raimondi, Susana C.; Choi, John K.; Downing, James R.; Pui, Ching-Hon] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA. [Raimondi, Susana C.; Ribeiro, Raul C.; Pui, Ching-Hon; Rubnitz, Jeffrey E.; Inaba, Hiroto] Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Coll Med, Memphis, TN 38163 USA. [Dahl, Gary V.] Lucile Packard Childrens Hosp, Div Hematol Oncol, Palo Alto, CA USA. [Dahl, Gary V.] Stanford Canc Ctr, Palo Alto, CA USA. [Bowman, William Paul] Cook Childrens Med Ctr, Div Hematol Oncol, Ft Worth, TX USA. [Taub, Jeffrey W.] Childrens Hosp Michigan, Div Hematol Oncol, Detroit, MI 48201 USA. [Degar, Barbara] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Leung, Wing] St Jude Childrens Res Hosp, Dept Bone Marrow Transplantat & Cellular Therapy, Memphis, TN 38105 USA. RP Inaba, H (reprint author), St Jude Childrens Res Hosp, Dept Oncol, MS 260,262 Danny Thomas Pl, Memphis, TN 38105 USA. EM hiroto.inaba@stjude.org OI Karol, Seth/0000-0001-8113-8180 FU Cancer Center Core Grant from the National Institutes of Health [CA21765]; American Lebanese Syrian Associated Charities (ALSAC) FX This study was supported, in part, by Cancer Center Core Grant CA21765 from the National Institutes of Health and by the American Lebanese Syrian Associated Charities (ALSAC). Dr. Pui is an American Cancer Society Professor. The authors thank Soheil Meshinchi, MD, PhD (Fred Hutchinson Cancer Research Center, Seattle, WA) and Gladstone Airewele, MD (Texas Children's Cancer Center, Houston, TX) for entering patients in AML02 and Cherise Guess (St. Jude) for editorial assistance. NR 32 TC 5 Z9 6 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2015 VL 168 IS 1 BP 94 EP 101 DI 10.1111/bjh.13107 PG 8 WC Hematology SC Hematology GA AW2YD UT WOS:000346151600012 PM 25164427 ER PT J AU Boros, E Bowen, AM Josephson, L Vasdev, N Holland, JP AF Boros, Eszter Bowen, Alice M. Josephson, Lee Vasdev, Neil Holland, Jason P. TI Chelate-free metal ion binding and heat-induced radiolabeling of iron oxide nanoparticles SO CHEMICAL SCIENCE LA English DT Article ID MR CONTRAST AGENTS; IN-VIVO; CANCER-THERAPY; PHYSICOCHEMICAL PROPERTIES; MAGNETIC NANOPARTICLES; CARBON NANOTUBES; DELIVERY; DEXTRAN; DRUGS; ZR-89-TRANSFERRIN AB A novel reaction for chelate-free, heat-induced metal ion binding and radiolabeling of ultra-small paramagnetic iron oxide nanoparticles (USPIOs) has been established. Radiochemical and non-radioactive labeling studies demonstrated that the reaction has a wide chemical scope and is applicable to p-, d- and f-block metal ions with varying ionic sizes and formal oxidation states from 2+ to 4+. Radiolabeling studies found that Zr-89-Feraheme (Zr-89-FH or Zr-89-ferumoxytol) can be isolated in 93 +/- 3% radiochemical yield (RCY) and >98% radiochemical purity using size-exclusion chromatography. Zr-89-FH was found to be thermodynamically and kinetically stable in vitro using a series of ligand challenge and plasma stability tests, and in vivo using PET/CT imaging and biodistribution studies in mice. Remarkably, ICP-MS and radiochemistry experiments showed that the same reaction conditions used to produce Zr-89-FH can be employed with different radionuclides to yield Cu-64-FH (66 +/- 6% RCY) and In-111-FH (91 +/- 2% RCY). Electron magnetic resonance studies support a mechanism of binding involving metal ion association with the surface of the magnetite crystal core. Collectively, these data suggest that chelate-free labeling methods can be employed to facilitate clinical translation of a new class of multimodality PET/MRI radiotracers derived from metal-based nanoparticles. Further, this discovery is likely to have broader implications in drug delivery, metal separation science, ecotoxicology of nanoparticles and beyond. C1 [Boros, Eszter] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Boros, Eszter; Vasdev, Neil; Holland, Jason P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Bowen, Alice M.] Goethe Univ Frankfurt, Inst Phys & Theoret Chem, Ctr Biomol Magnet Resonance BMRZ, D-60438 Frankfurt, Germany. [Josephson, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Adv Mol Imaging Sci, Charlestown, MA 02129 USA. [Vasdev, Neil; Holland, Jason P.] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. RP Holland, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM holland.jason@mgh.harvard.edu OI Holland, Jason/0000-0002-0066-219X FU Australian National Science and Technology Organisation (ANSTO, Sydney, Australia); Swiss National Science Foundation; Goethe International Postdoc Programme Fellowship (EU project GO-IN) [291776] FX We thank Dr T. Lee Collier, Dr Cory Daignault and David Hill for helpful discussions, and Alicia Leece for technical advice regarding PET/CT. We thank Dr Ron Moore, Dr Jack A. Correia and David Lee and the Massachusetts General Hospital Cyclotron Core facility for target irradiations. We are indebted to Dr Bruce Wieland and Dr Matthew Stokely (BruceTech Targets) for design and production of the custom-made solid metal target for the GE PETtrace cyclotron. We thank Dr Peter Caravan for providing access to the ICP-MS instrumentation. We thank Prof. Thomas Prisner for access to EMR instrumentation. We are grateful to William J. Cupelo and Dr Jack Hoppin (inviCRO, LLC, Boston, MA) for generous support and access to the VivoQuant software. We thank Dr Ivan Greguric and the Australian National Science and Technology Organisation (ANSTO, Sydney, Australia) for providing financial support (JPH). We are grateful to the Swiss National Science Foundation for an advanced Postdoctoral mobility fellowship (EB). AMB gratefully acknowledges the support of a Goethe International Postdoc Programme Fellowship (EU project GO-IN, No. 291776 (COFUND) FP7 Marie Curie Action). NR 49 TC 22 Z9 22 U1 6 U2 37 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2041-6520 EI 2041-6539 J9 CHEM SCI JI Chem. Sci. PY 2015 VL 6 IS 1 BP 225 EP 236 DI 10.1039/c4sc02778g PG 12 WC Chemistry, Multidisciplinary SC Chemistry GA AU9HD UT WOS:000345901600022 ER PT J AU Wagner, FF Zhang, YL Fass, DM Joseph, N Gale, JP Weiwer, M McCarren, P Fisher, SL Kaya, T Zhao, WN Reis, SA Hennig, KM Thomas, M Lemercier, BC Lewis, MC Guan, JS Moyer, MP Scolnick, E Haggarty, SJ Tsai, LH Holson, EB AF Wagner, F. F. Zhang, Y. -L. Fass, D. M. Joseph, N. Gale, J. P. Weiwer, M. McCarren, P. Fisher, S. L. Kaya, T. Zhao, W. -N. Reis, S. A. Hennig, K. M. Thomas, M. Lemercier, B. C. Lewis, M. C. Guan, J. S. Moyer, M. P. Scolnick, E. Haggarty, S. J. Tsai, L. -H. Holson, E. B. TI Kinetically selective inhibitors of histone deacetylase 2 (HDAC2) as cognition enhancers SO CHEMICAL SCIENCE LA English DT Article ID SYNAPTIC PLASTICITY; MOUSE MODEL; MEMORY; BRAIN; NEURODEGENERATION; ACETYLATION; EXTINCTION; EXPRESSION; P25/CDK5; DEFICITS AB Aiming towards the development of novel nootropic therapeutics to address the cognitive impairment common to a range of brain disorders, we set out to develop highly selective small molecule inhibitors of HDAC2, a chromatin modifying histone deacetylase implicated in memory formation and synaptic plasticity. Novel ortho-aminoanilide inhibitors were designed and evaluated for their ability to selectively inhibit HDAC2 versus the other Class I HDACs. Kinetic and thermodynamic binding properties were essential elements of our design strategy and two novel classes of ortho-aminoanilides, that exhibit kinetic selectivity (biased residence time) for HDAC2 versus the highly homologous isoform HDAC1, were identified. These kinetically selective HDAC2 inhibitors (BRD6688 and BRD4884) increased H4K12 and H3K9 histone acetylation in primary mouse neuronal cell culture assays, in the hippocampus of CK-p25 mice, a model of neurodegenerative disease, and rescued the associated memory deficits of these mice in a cognition behavioural model. These studies demonstrate for the first time that selective pharmacological inhibition of HDAC2 is feasible and that inhibition of the catalytic activity of this enzyme may serve as a therapeutic approach towards enhancing the learning and memory processes that are affected in many neurological and psychiatric disorders. C1 [Wagner, F. F.; Zhang, Y. -L.; Fass, D. M.; Joseph, N.; Gale, J. P.; Weiwer, M.; McCarren, P.; Kaya, T.; Zhao, W. -N.; Reis, S. A.; Hennig, K. M.; Thomas, M.; Lemercier, B. C.; Lewis, M. C.; Guan, J. S.; Moyer, M. P.; Scolnick, E.; Haggarty, S. J.; Tsai, L. -H.; Holson, E. B.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Joseph, N.; Guan, J. S.; Tsai, L. -H.] MIT, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. [Fass, D. M.; Fisher, S. L.] SL Fisher Consulting LLC, Framingham, MA USA. [Zhao, W. -N.; Reis, S. A.; Hennig, K. M.; Haggarty, S. J.] Harvard Univ, Massachusetts Gen Hosp, Ctr Human Genet Res, Chem Neurobiol Lab,Dept Neurol & Psychiat,Med Sch, Boston, MA USA. RP Holson, EB (reprint author), Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, 415 Main St, Cambridge, MA 02142 USA. EM edholson@broadinstitute.org OI Guan, Ji-Song /0000-0001-5219-0289; Haggarty, Stephen J./0000-0002-7872-168X FU Stanley Medical Research Institute; JPB Foundation; NIH/NIDA [R01DA028301] FX This research was funded by the Stanley Medical Research Institute, the JPB Foundation (L.H.T.) and the NIH/NIDA (S.J.H., R01DA028301) NR 41 TC 17 Z9 18 U1 1 U2 24 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2041-6520 EI 2041-6539 J9 CHEM SCI JI Chem. Sci. PY 2015 VL 6 IS 1 BP 804 EP 815 DI 10.1039/c4sc02130d PG 12 WC Chemistry, Multidisciplinary SC Chemistry GA AU9HD UT WOS:000345901600098 PM 25642316 ER PT J AU Girard, MJA Dupps, WJ Baskaran, M Scarcelli, G Yun, SH Quigley, HA Sigal, IA Strouthidis, NG AF Girard, Michael J. A. Dupps, William J. Baskaran, Mani Scarcelli, Giuliano Yun, Seok H. Quigley, Harry A. Sigal, Ian A. Strouthidis, Nicholas G. TI Translating Ocular Biomechanics into Clinical Practice: Current State and Future Prospects SO CURRENT EYE RESEARCH LA English DT Review DE Brillouin microscopy; intraocular pressure; ocular biomechanics; optical coherence tomography; ophthalmic pathologies; personalised medicine; translational biomechanics ID OPTIC-NERVE HEAD; OPEN-ANGLE GLAUCOMA; FINITE-ELEMENT-ANALYSIS; COLLAGEN CROSS-LINKING; ELEVATED INTRAOCULAR-PRESSURE; LAMINA-CRIBROSA DISPLACEMENT; COHERENCE TOMOGRAPHY IMAGES; TRABECULAR MESHWORK CELLS; ACOUSTIC RADIATION FORCE; CORNEAL ELASTIC-MODULUS AB Biomechanics is the study of the relationship between forces and function in living organisms and is thought to play a critical role in a significant number of ophthalmic disorders. This is not surprising, as the eye is a pressure vessel that requires a delicate balance of forces to maintain its homeostasis. Over the past few decades, basic science research in ophthalmology mostly confirmed that ocular biomechanics could explain in part the mechanisms involved in almost all major ophthalmic disorders such as optic nerve head neuropathies, angle closure, ametropia, presbyopia, cataract, corneal pathologies, retinal detachment and macular degeneration. Translational biomechanics in ophthalmology, however, is still in its infancy. It is believed that its use could make significant advances in diagnosis and treatment. Several translational biomechanics strategies are already emerging, such as corneal stiffening for the treatment of keratoconus, and more are likely to follow. This review aims to cultivate the idea that biomechanics plays a major role in ophthalmology and that the clinical translation, lead by collaborative teams of clinicians and biomedical engineers, will benefit our patients. Specifically, recent advances and future prospects in corneal, iris, trabecular meshwork, crystalline lens, scleral and lamina cribrosa biomechanics are discussed. C1 [Girard, Michael J. A.] Natl Univ Singapore, Dept Biomed Engn, In Vivo Biomech Lab, Singapore 117576, Singapore. [Girard, Michael J. A.; Baskaran, Mani; Strouthidis, Nicholas G.] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore. [Dupps, William J.] Cleveland Clin, Dept Ophthalmol Biomed Engn & Transplant, Cole Eye Inst, Cleveland, OH 44106 USA. [Dupps, William J.] Cleveland Clin, Lerner Res Inst, Cleveland, OH 44106 USA. [Scarcelli, Giuliano; Yun, Seok H.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Scarcelli, Giuliano; Yun, Seok H.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Cambridge, MA USA. [Quigley, Harry A.] Johns Hopkins Univ, Sch Med, Wilmer Inst, Baltimore, MD 21205 USA. [Sigal, Ian A.] Univ Pittsburgh, Sch Med, Dept Ophthalmol,Ophthalmol & Visual Sci Res Ctr, UPMC Eye Ctr,Eye & Ear Inst, Pittsburgh, PA 15261 USA. [Sigal, Ian A.] Univ Pittsburgh, Swanson Sch Engn, Dept Bioengn, Pittsburgh, PA USA. [Strouthidis, Nicholas G.] Moorfields Eye Hosp NHS Fdn Trust, NIHR Biomed Res Ctr, London, England. [Strouthidis, Nicholas G.] UCL Inst Ophthalmol, London, England. RP Girard, MJA (reprint author), Natl Univ Singapore, Dept Biomed Engn, In Vivo Biomech Lab, 9 Engn Dr 1,Block EA 03-12, Singapore 117576, Singapore. EM mgirard@nus.edu.sg RI Girard, Michael/F-9323-2015; OI Girard, Michael/0000-0003-4408-5918; scarcelli, giuliano/0000-0002-1736-077X; Dupps, William/0000-0003-0761-8658 FU Singapore Ministry of Education, Academic Research Fund; NUS [NUSYIA_FY13_P03]; Department of Health through UK National Institute for Health Research; UCL Institute of Ophthalmology for a Biomedical Research Centre for Ophthalmology; National Institutes of Health [R01-EY023966, P30-EY008098]; NIH [P41-EB015903, R21EY023043, K25EB015885, R01 EY023381]; Harvard Clinical and Translational Science Center (NIH) [UL1-RR025758]; National Keratoconus Foundation/Discovery Eye Foundation; Research to Prevent Blindness; Cleveland Clinic Lerner College of Medicine of Case Western Reserve University; Avedro; Zeiss; Topcon FX MJAG acknowledges support from the Singapore Ministry of Education, Academic Research Fund, Tier 1 and from a NUS Young Investigator Award (NUSYIA_FY13_P03). Acknowledgment is also made to the donors of the NGR, a program of the Bright Focus Foundation (formerly American Health Assistance Foundation or AHAF). NGS acknowledges a proportion of his financial support from the Department of Health through the award made by the UK National Institute for Health Research to Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology for a Biomedical Research Centre for Ophthalmology. The views expressed in this publication are those of the authors and not necessarily those of the UK Department of Health. IAS acknowledges support from the National Institutes of Health grants R01-EY023966 and P30-EY008098. SHY and GS acknowledge support (in part) by NIH P41-EB015903, R21EY023043, K25EB015885, and the Harvard Clinical and Translational Science Center (NIH UL1-RR025758). WJD acknowledges support in part by NIH R01 EY023381, the National Keratoconus Foundation/Discovery Eye Foundation, Unrestricted and Challenge Grants from Research to Prevent Blindness to the Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University. WJD is a recipient of a Research to Prevent Blindness Career Development Award. SHY and GS are listed as inventors on intellectual property held by Massachusetts General Hospital related to biomechanical measurement. WJD is listed as an inventor on intellectual property held by Cleveland Clinic related to biomechanical measurement and modeling and has received research funding and royalties related to use of IP from Avedro, Zeiss and Topcon. WJD is a consultant to Ziemer. NR 207 TC 15 Z9 15 U1 3 U2 39 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0271-3683 EI 1460-2202 J9 CURR EYE RES JI Curr. Eye Res. PD JAN PY 2015 VL 40 IS 1 BP 1 EP 18 DI 10.3109/02713683.2014.914543 PG 18 WC Ophthalmology SC Ophthalmology GA AW0IA UT WOS:000345973700001 PM 24832392 ER PT J AU Paulus, GLC Xavier, RJ AF Paulus, Geraldine L. C. Xavier, Ramnik J. TI Autophagy and checkpoints for intracellular pathogen defense SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Review DE autophagy; interferon gamma-mediated pathogen elimination; LC3-associated phagocytosis; pathogen survival strategies; xenophagy ID INTESTINAL EPITHELIAL-CELLS; SELECTIVE AUTOPHAGY; INNATE IMMUNITY; CROHNS-DISEASE; ANTIBACTERIAL AUTOPHAGY; BACTERIAL PATHOGENS; TOXOPLASMA-GONDII; CARGO RECEPTORS; ATG PROTEINS; INFECTION AB Purpose of review Autophagy plays a crucial role in intracellular defense against various pathogens. Xenophagy is a form of selective autophagy that targets intracellular pathogens for degradation. In addition, several related, yet distinct, intracellular defense responses depend on autophagy-related genes. This review gives an overview of these processes, pathogen strategies to subvert them, and their crosstalk with various cell death programs. Recent findings The recruitment of autophagy-related proteins plays a key role in multiple intracellular defense programs, specifically xenophagy, microtubule-associated protein 1 light chain 3 alpha (LC3)-associated phagocytosis, and the interferon gamma-mediated elimination of pathogens, such as Toxoplasma gondii and murine norovirus. Recent progress has revealed methods employed by pathogens to resist these intracellular defense mechanisms and/or persist in spite of them. The intracellular pathogen load can tip the balance between cell survival and cell death. Further, it was recently observed that LC3-associated phagocytosis is indispensable for the efficient clearance of dying cells. Summary Autophagy-dependent and autophagy-related gene-dependent pathways are essential in intracellular defense against a broad range of pathogens. C1 [Paulus, Geraldine L. C.; Xavier, Ramnik J.] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. [Paulus, Geraldine L. C.; Xavier, Ramnik J.] MIT, Cambridge, MA 02139 USA. [Paulus, Geraldine L. C.; Xavier, Ramnik J.] Harvard Univ, Sch Med, Gastrointestinal Unit, Ctr Study Inflammatory Bowel Dis, Boston, MA USA. [Paulus, Geraldine L. C.; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA. RP Xavier, RJ (reprint author), Massachusetts Gen Hosp, Richard B Simches Res Ctr, Gastrointestinal Unit, 185 Cambridge St, Boston, MA 02114 USA. EM xavier@molbio.mgh.harvard.edu FU Crohn's and Colitis Foundation of America; Leona M. and Harry B. Helmsley Charitable Trust; NIH [DK097485, DK043351] FX This work was supported by funding from the Crohn's and Colitis Foundation of America, the Leona M. and Harry B. Helmsley Charitable Trust, and NIH grants DK097485 and DK043351 (to R.J.X.). NR 88 TC 8 Z9 8 U1 0 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 EI 1531-7056 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD JAN PY 2015 VL 31 IS 1 BP 14 EP 23 DI 10.1097/MOG.0000000000000134 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AW2MA UT WOS:000346121000003 PM 25394238 ER PT J AU Xi, YN Liu, SM Bettaieb, A Matsuo, K Matsuo, I Hosein, E Chahed, S Wiede, F Zhang, S Zhang, ZY Kulkarni, RN Tiganis, T Haj, FG AF Xi, Yannan Liu, Siming Bettaieb, Ahmed Matsuo, Kosuke Matsuo, Izumi Hosein, Ellen Chahed, Samah Wiede, Florian Zhang, Sheng Zhang, Zhong-Yin Kulkarni, Rohit N. Tiganis, Tony Haj, Fawaz G. TI Pancreatic T cell protein-tyrosine phosphatase deficiency affects beta cell function in mice SO DIABETOLOGIA LA English DT Article DE Insulin secretion; Ptpn2; STAT1; STAT3; Tcell protein-tyrosine phosphatase; Type 2 diabetes ID TRANSCRIPTION FACTOR STAT3; GLUCOSE-INTOLERANCE; INSULIN-RESISTANCE; SIGNAL TRANSDUCER; KNOCKOUT MICE; NEGATIVE REGULATOR; CANDIDATE GENE; RECEPTOR; MOUSE; SECRETION AB Aims/hypothesis T cell protein tyrosine phosphatase (TCPTP, encoded by PTPN2) regulates cytokine-induced pancreatic beta cell apoptosis and may contribute to the pathogenesis of type 1 diabetes. However, the role of TCPTP in pancreatic endocrine function and insulin secretion remains largely unknown. Methods To investigate the endocrine role of pancreatic TCPTP we generated mice with pancreas Ptpn2/TCPTP deletion (panc-TCPTP KO). Results When fed regular chow, panc-TCPTP KO and control mice exhibited comparable glucose tolerance. However, when challenged with prolonged high fat feeding panc-TCPTP KO mice exhibited impaired glucose tolerance and attenuated glucose-stimulated insulin secretion (GSIS). The defect in GSIS was recapitulated in primary islets ex vivo and after TCPTP pharmacological inhibition or lentiviral-mediated TCPTP knockdown in the glucose-responsive MIN6 beta cells, consistent with this being cell autonomous. Reconstitution of TCPTP in knockdown cells reversed the defect in GSIS demonstrating that the defect was a direct consequence of TCPTP deficiency. The reduced insulin secretion in TCPTP knockdown MIN6 beta cells was associated with decreased insulin content and glucose sensing. Furthermore, TCPTP deficiency led to enhanced tyrosyl phosphorylation of signal transducer and activator of transcription 1 and 3 (STAT 1/3), and substrate trapping studies in MIN6 beta cells identified STAT 1/3 as TCPTP substrates. STAT3 pharmacological inhibition and small interfering RNA-mediated STAT3 knockdown in TCPTP deficient cells restored GSIS to control levels, indicating that the effects of TCPTP deficiency were mediated, at least in part, through enhanced STAT3 phosphorylation and signalling. Conclusions/interpretation These studies identify a novel role for TCPTP in insulin secretion and uncover STAT3 as a physiologically relevant target for TCPTP in the endocrine pancreas. C1 [Xi, Yannan; Liu, Siming; Bettaieb, Ahmed; Matsuo, Kosuke; Matsuo, Izumi; Hosein, Ellen; Chahed, Samah; Haj, Fawaz G.] Univ Calif Davis, Dept Nutr, Davis, CA 95616 USA. [Wiede, Florian; Zhang, Sheng] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic, Australia. [Zhang, Sheng; Zhang, Zhong-Yin] Indiana Univ, Dept Biochem & Mol Biol, Indianapolis, IN 46204 USA. [Kulkarni, Rohit N.] Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. [Haj, Fawaz G.] Univ Calif Davis, Dept Internal Med, Div Endocrinol Diabet & Metab, Sacramento, CA 95817 USA. [Haj, Fawaz G.] Univ Calif Davis, Ctr Comprehens Canc, Sacramento, CA 95817 USA. RP Haj, FG (reprint author), Univ Calif Davis, Dept Nutr, 3135 Meyer Hall, Davis, CA 95616 USA. EM fghaj@ucdavis.edu FU Juvenile Diabetes Research Foundation [1-2009-337]; National Institutes of Health (NIH) [R56 DK084317, R01 DK090492, R01 DK095359, K99 DK100736]; NIH [R01 DK67536, R01 DK103215]; Zhang laboratory [R01 CA69202]; National Health and Medical Research Council (NHMRC) of Australia [APP1047055] FX This work was supported by a research grant from the Juvenile Diabetes Research Foundation (1-2009-337) and National Institutes of Health (NIH) grants R56 DK084317, R01 DK090492 and R01 DK095359 to FGH and K99 DK100736 to AB. Research in the Kulkarni laboratory is funded by NIH grants R01 DK67536 and R01 DK103215, Zhang laboratory by R01 CA69202 and the Tiganis laboratory by the National Health and Medical Research Council (NHMRC) of Australia (APP1047055). T. Tiganis is an NHMRC Principal Research Fellow (APP1002693). NR 50 TC 2 Z9 2 U1 1 U2 9 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 2015 VL 58 IS 1 BP 122 EP 131 DI 10.1007/s00125-014-3413-7 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AW1AI UT WOS:000346022300017 PM 25338551 ER PT J AU Barshop, K Kuo, B AF Barshop, Kenneth Kuo, Braden TI The investigational drug camicinal for the treatment of gastroparesis SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Article DE camicinal; gastroparesis; GSK962040; motility ID MOTILIN RECEPTOR AGONISTS; DOUBLE-BLIND; DIABETIC GASTROPARESIS; ORAL ERYTHROMYCIN; METOCLOPRAMIDE; MANAGEMENT; GSK962040; GHRELIN; STOMACH; AZITHROMYCIN AB Introduction: Gastroparesis is a syndrome of delayed gastric emptying in the absence of mechanical obstruction that presents with upper gastrointestinal symptoms. Despite its growing prevalence, there remains an unmet clinical need for more efficacious prokinetic treatment options. The current market includes prokinetic agents that reduce gastroparesis symptoms. However, adverse drug effects and tachyphylaxis with repeated dosing are among the factors that limit their use. Camicinal (GSK962040) is the most advanced, small-molecule, selective motilin receptor agonist with therapeutic potential to date. Areas covered: This article reviews the literature on the limitations of current prokinetic agents used in the treatment of gastroparesis. It also summarizes the current evidence and influential clinical trial results involving the investigational drug camicinal, and shares its preliminary findings from the literature. Expert opinion: Camicinal represents a new opportunity as a treatment in a clinical area in need of new agents. There is emerging literature to support how the drug addresses both gastroparesis symptoms and dysmotility with no significant adverse effects or tachyphylaxis reported to date. Challenges remain in getting a new compound approved for gastroparesis. However, careful design of future trials will help to continue the record of success camicinal trials have had thus far. C1 [Barshop, Kenneth] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. [Kuo, Braden] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. RP Kuo, B (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, 55 Fruit St, Boston, MA 02114 USA. EM braden.kuo@gmail.com NR 50 TC 3 Z9 3 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3784 EI 1744-7658 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD JAN PY 2015 VL 24 IS 1 BP 133 EP 140 DI 10.1517/13543784.2015.975792 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AW1WL UT WOS:000346079100011 ER PT J AU Kubinski, SN McQueen, CA Sittloh, KA Dean, JC AF Kubinski, Samantha N. McQueen, Christina A. Sittloh, Keir A. Dean, Jesse C. TI Walking with wider steps increases stance phase gluteus medius activity SO GAIT & POSTURE LA English DT Article DE Biomechanics; Gluteus medius; Hip abduction; Locomotion; Step width ID BALANCE; STABILIZATION; COORDINATION; INDICATORS; STABILITY; TREADMILL; STRATEGY; STROKE; ADULTS; SPEED AB Increases in step width have been reported for several clinical populations, including older adults and stroke survivors. These populations often also exhibit decreased hip abductor strength, suggesting that walking with wider steps may be an adaptive response in order to reduce the mechanical demands on the hip abductors. The purpose of this study was to quantify the relationship between step width and gluteus medius (GM) activity during walking. Fourteen young, uninjured adults walked on a treadmill at 1.25 m/s for four step width conditions (Normal, Narrow, Medium, and Wide) while step width and stance phase GM electromyographic (EMG) activity were quantified. We also measured hip abduction torque and GM activity during maximum voluntary isometric contractions (MVICs) at three hip angles (neutral, abducted 108, and abducted 20 degrees). During walking trials, GM activity was significantly (p < 0.0001) influenced by step width; compared to Normal walking, GM activity was 47% higher with Wide steps and 24% lower with Narrow steps. We also observed a weak positive correlation (r = 0.18 +/- 0.14) between step width and GM activity during Normal walking, as GM activity was higher with wider steps. These results cannot be attributed to changes in GM conformation under the recording electrode, as GM activity was not influenced by hip angle during MVICs. The increased GM activity with wider steps does not support the proposal that increasing step width would be a beneficial adaptation to weakened hip abductors. A likely alternative explanation is that increased step width is a response to decreased gait balance. Published by Elsevier B.V. C1 [Kubinski, Samantha N.; McQueen, Christina A.; Sittloh, Keir A.; Dean, Jesse C.] Med Univ S Carolina, Coll Hlth Profess, Div Phys Therapy, Charleston, SC 29425 USA. [Dean, Jesse C.] Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC 29403 USA. RP Dean, JC (reprint author), 77 President St,MSC700, Charleston, SC 29425 USA. EM deaje@musc.edu OI Dean, Jesse/0000-0003-2034-4217 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development Service [IK2 RX000750]; National Institutes of Health [R21 HD064964] FX This work was partially supported by grants from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development Service (IK2 RX000750) and the National Institutes of Health (R21 HD064964). The funding sources had no involvement in the study design; collection, analysis, and interpretation of data; writing of the manuscript; or decision to submit the manuscript for publication. The contents of this manuscript do not represent the views of the Department of Veterans Affairs or the United States Government. NR 30 TC 5 Z9 5 U1 0 U2 15 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 2015 VL 41 IS 1 BP 130 EP 135 DI 10.1016/j.gaitpost.2014.09.013 PG 6 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA AW2MQ UT WOS:000346122800023 PM 25300241 ER PT J AU Provost, SM Lanham, HJ Leykum, LK McDaniel, RR Pugh, J AF Provost, Shannon M. Lanham, Holly J. Leykum, Luci K. McDaniel, Reuben R., Jr. Pugh, Jacqueline TI Health care huddles: Managing complexity to achieve high reliability SO HEALTH CARE MANAGEMENT REVIEW LA English DT Article DE complex adaptive systems; conversation; health care huddles; high reliability organizations; relationships ID CULTURE; ORGANIZATIONS; HOSPITALS; DYNAMICS; SAFETY; SYSTEM AB Background: Health care huddles are increasingly employed in a range of formats but theoretical mechanisms underlying huddles remain relatively uncharted. Purpose: A complexity science view implies that essential managerial strategies for high-performing health care organizations include meaningful conversations, enhanced relationships, and a learning culture. These three dimensions informed our approach to studying huddles. We explore new theories for how and why huddles have been useful in health care organizations. Methods: We used a study design incorporating literature review, direct observation, and semistructured interviews. A complexity science framework guided data collection in three health care settings; we also incorporated theories on high-reliability organizations to analyze our observations and interpret huddle participants' perspectives. Findings: We identify theoretical paths that could link huddles to improvement in patient safety outcomes. Huddles create time and space for conversations, enhance relationships, and strengthen a culture of safety. Huddles can be of particular value to health care organizations seeking or sustaining high reliability. Practice Implications: Achieving high reliability, the organizational capacity to deliver what is intended to be delivered every time is difficult in complex systems. Managers have potential to create conditions from which huddle outcomes that support high reliability are more likely to emerge. Huddles support efforts to improve patient safety when they afford opportunities for heedful interactions to take place among individuals caring for patients and embed mindfulness into the organization. C1 [Provost, Shannon M.; Lanham, Holly J.] Univ Texas Austin, Dept Informat Risk & Operat Management, McCombs Sch Business, Austin, TX 78712 USA. [Lanham, Holly J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Leykum, Luci K.] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, Dept Med, San Antonio, TX 78229 USA. [McDaniel, Reuben R., Jr.] Univ Texas Austin, McCombs Sch Business, Austin, TX 78712 USA. [Pugh, Jacqueline] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Pugh, Jacqueline] South Texas Vet Hlth Care Syst, Res, San Antonio, TX USA. RP Provost, SM (reprint author), Univ Texas Austin, Dept Informat Risk & Operat Management, McCombs Sch Business, Austin, TX 78712 USA. EM shannon.provost@phd.mccombs.utexas.edu OI Pugh, Jacqueline/0000-0003-4933-141X NR 49 TC 5 Z9 5 U1 2 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0361-6274 EI 1550-5030 J9 HEALTH CARE MANAGE R JI Health Care Manage. Rev. PD JAN-MAR PY 2015 VL 40 IS 1 BP 2 EP 12 DI 10.1097/HMR.0000000000000009 PG 11 WC Health Policy & Services SC Health Care Sciences & Services GA AW2LW UT WOS:000346120400002 PM 24589926 ER PT J AU Mohajerani, P Tzoumas, S Rosenthal, A Ntziachristos, V AF Mohajerani, Pouyan Tzoumas, Stratis Rosenthal, Amir Ntziachristos, Vasilis TI Optical and Optoacoustic Model-Based Tomography [Theory and current challenges for deep tissue imaging of optical contrast] SO IEEE SIGNAL PROCESSING MAGAZINE LA English DT Article ID RAY COMPUTED-TOMOGRAPHY; PHOTOACOUSTIC TOMOGRAPHY; BORN RATIO; MOLECULAR TOMOGRAPHY; FLUORESCENCE; RECONSTRUCTION; REGULARIZATION; INVERSION; IMAGES; LIGHT C1 [Tzoumas, Stratis] Tech Univ Munich, Inst Biol & Med Imaging, D-80290 Munich, Germany. [Rosenthal, Amir] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Rosenthal, Amir] Harvard Univ, Sch Med, Boston, MA USA. [Ntziachristos, Vasilis] Harvard Univ, Boston, MA 02115 USA. [Ntziachristos, Vasilis] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ntziachristos, Vasilis] Helmholtz Zentrum Munchen, Inst Biol & Med Imaging, Munich, Germany. RP Mohajerani, P (reprint author), Helmholtz Zentrum Munchen, Inst Biol & Med Imaging, Munich, Germany. EM pouyan.mohajerani@gmail.com; strtzoumas@gmail.com; eeamir@gmail.com; v.ntziachristos@tum.de RI Magazine, Signal Processing/E-9947-2015 NR 55 TC 5 Z9 5 U1 1 U2 17 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1053-5888 EI 1558-0792 J9 IEEE SIGNAL PROC MAG JI IEEE Signal Process. Mag. PD JAN PY 2015 VL 32 IS 1 BP 88 EP 100 DI 10.1109/MSP.2014.2352672 PG 13 WC Engineering, Electrical & Electronic SC Engineering GA AW1IR UT WOS:000346043800015 ER PT J AU Winer, I Ahmed, QF Mert, I Bandyopadhyay, S Cote, M Munkarah, AR Hussein, Y Al-Wahab, Z Elshaikh, MA Alosh, B Schultz, DS Mahdi, H Nucci, MR Van de Vijver, KK Morris, RT Oliva, E Ali-Fehmi, R AF Winer, Ira Ahmed, Quratulain F. Mert, Ismail Bandyopadhyay, Sudeshna Cote, Michele Munkarah, Adnan R. Hussein, Yaser Al-Wahab, Zaid Elshaikh, Mohamed A. Alosh, Baraa Schultz, Daniel S. Mahdi, Haider Nucci, Marisa R. Van de Vijver, Koen K. Morris, Robert T. Oliva, Esther Ali-Fehmi, Rouba TI Significance of Lymphovascular Space Invasion in Uterine Serous Carcinoma: What Matters More; Extent or Presence? SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE Lymphovascular space invasion; Uterine serous carcinoma ID PATHOLOGICAL RISK-FACTORS; SQUAMOUS-CELL CARCINOMA; ENDOMETRIAL CANCER; PROGNOSTIC-SIGNIFICANCE; CERVICAL-CANCER; BREAST-CANCER; INVOLVEMENT; ADENOCARCINOMA; INTERMEDIATE; HYSTERECTOMY AB To analyze the clinical significance of the extent of lymphovascular space invasion (LVI) in patients with uterine serous carcinoma. After IRB approval, 232 patients with uterine serous carcinoma from the pathology databases of 4 large academic institutions were included. Patients were divided into 3 groups based on extent of LVI. Extensive LVI (E-LVI) was defined as >= 3 vessel involvement; low LVI (L-LVI) was defined <3 vessel involvement; and the third group consisted of tumors with no LVI (A-LVI). The association between LVI and myometrial invasion, cervical involvement, lower uterine segment involvement, positive peritoneal washings, lymph node involvement, stage, and survival were analyzed. Of 232 patients, 47 had E-LVI (20.3%), 83 had L-LVI (35.8%), and 102 had A-LVI (44%). A total of 9.8% of the patients with A-LVI had lymph node involvement as compared with 18.1% in the L-LVI group and 55.4% in the E-LVI group (P<0.0001). Fifty-nine percent of the patients in A-LVI, 85% in L-LVI, and 100% in the E-LVI group demonstrated myometrial invasion (P<0.0001). Cervical involvement was noted in 23%, 43%, 66% (P<0.0001) and lower uterine segment involvement involvement in 31%, 43%, and 42% of A-LVI, L-LVI, and E-LVI (P<0.0001), respectively. Stage III and IV disease were seen in 29%, 38%, and 79% of the patients with A-LVI, L-LVI, and E-LVI, respectively (P<0.0001). The median overall survival was 172, 95, and 39 mo for the A-LVI, L-LVI, and E-LVI groups, respectively (P<0.0001). The racial distribution was significant with African American patients demonstrating significantly more L-LVI (27.8%) and E-LVI (40.4%) when compared with A-LVI (19.6%) (P=0.040). In a subgroup analysis including patients with Stage I and II (n=123) revealed median survivals of 172, 169, and 38mo in the A-LVI, L-LVI, and E-LVI groups, respectively (P<0.0001). Fifty percent of these patients with E-LVI, 20% in L-LVI group, and 15% in A-LVI group had disease recurrence (P=0.040). The extent of LVI was associated with multiple pathologic factors and was found to be a negative prognostic factor for overall survival and disease recurrence. C1 [Winer, Ira; Ahmed, Quratulain F.; Mert, Ismail; Bandyopadhyay, Sudeshna; Cote, Michele; Al-Wahab, Zaid; Alosh, Baraa; Morris, Robert T.] Wayne State Univ, Detroit, MI 48202 USA. [Munkarah, Adnan R.; Elshaikh, Mohamed A.; Schultz, Daniel S.] Henry Ford Hosp, Detroit, MI USA. [Hussein, Yaser] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Mahdi, Haider] Cleveland Clin, Cleveland, OH USA. [Nucci, Marisa R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Van de Vijver, Koen K.; Oliva, Esther] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ali-Fehmi, Rouba] Harper Univ Hosp, Dept Pathol, Detroit, MI 48201 USA. RP Ali-Fehmi, R (reprint author), Harper Univ Hosp, Dept Pathol, 3990 John R, Detroit, MI 48201 USA. EM rali@med.wayne.edu NR 31 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 EI 1538-7151 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JAN PY 2015 VL 34 IS 1 BP 47 EP 56 DI 10.1097/PGP.0000000000000113 PG 10 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA AW2XP UT WOS:000346150300009 PM 25473753 ER PT J AU Wright, JR Wold, LE Carney, JA Young, RH AF Wright, James R., Jr. Wold, Lester E. Carney, J. Aidan Young, Robert H. TI History of Gynecologic Pathology. XXVI: Dr Malcolm B. Dockerty SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE Medical history; Gynecologic pathology; History of pathology; Mayo Clinic ID SARCOMA-LIKE PROLIFERATIONS; STEIN-LEVENTHAL SYNDROME; GRANULOSA-CELL TUMOR; PAPILLARY OVARIAN TUMORS; ENDOMETRIAL CARCINOMA; STROMAL ENDOMETRIOSIS; UTERINE CERVIX; MESONEPHRIC CARCINOMA; UNUSUAL COEXISTENCE; ADOLESCENT GIRLS C1 [Wright, James R., Jr.] Univ Calgary, Calgary Lab Serv, Dept Pathol & Lab Med, Calgary, AB T2L 2K8, Canada. [Wold, Lester E.; Carney, J. Aidan] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Young, Robert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA USA. RP Wright, JR (reprint author), Univ Calgary, Calgary Lab Serv, Dept Pathol & Lab Med, 9,3535 Res Rd NW, Calgary, AB T2L 2K8, Canada. EM jim.wright@cls.ab.ca NR 165 TC 1 Z9 1 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-1691 EI 1538-7151 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JAN PY 2015 VL 34 IS 1 BP 101 EP 110 DI 10.1097/PGP.0000000000000176 PG 10 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA AW2XP UT WOS:000346150300015 PM 25473759 ER PT J AU Jia, HG Phipps, M Bravata, D Castro, J Li, XL Ordin, D Myers, J Vogel, WB Williams, L Chumbler, N AF Jia, Huanguang Phipps, Michael Bravata, Dawn Castro, Jaime Li, Xinli Ordin, Diana Myers, Jennifer Vogel, W. Bruce Williams, Linda Chumbler, Neale TI Inpatient stroke care quality for veterans: are there differences between Veterans Affairs medical centers in the stroke belt and other areas? SO INTERNATIONAL JOURNAL OF STROKE LA English DT Article DE acute stroke therapy; acute; ischemic stroke; stroke; facilities; stroke units; treatment ID CLINICAL-PRACTICE GUIDELINE; AMERICAN-HEART-ASSOCIATION; ACADEMY-OF-NEUROLOGY; ISCHEMIC-STROKE; UNITED-STATES; REHABILITATION CARE; MORTALITY; MANAGEMENT; COUNCIL; PROFESSIONALS AB Background Stroke mortality has been found to be much higher among residents in the stroke belt region than in the rest of United States, but it is not known whether differences exist in the quality of stroke care provided in Department of Veterans Affairs medical centers in states inside and outside this region. Objective We compared mortality and inpatient stroke care quality between Veterans Affairs medical centers inside and outside the stroke belt region. Methods Study patients were veterans hospitalized for ischemic stroke at 129 Veterans Affairs medical centers. Inpatient stroke care quality was assessed by 14 quality indicators. Multivariable logistic regression models were fit to examine differences in quality between facilities inside and outside the stroke belt, adjusting for patient characteristics and Veterans Affairs medical centers clustering effect. Results Among the 3909 patients, 28.1% received inpatient ischemic stroke care in 28 stroke belt Veterans Affairs medical centers, and 71.9% obtained care in 101 non-stroke belt Veterans Affairs medical centers. Patients cared for in stroke belt Veterans Affairs medical centers were more likely to be younger, Black, married, have a higher stroke severity, and less likely to be ambulatory pre-stroke. We found no statistically significant differences in short-and long-term post-admission mortality and inpatient care quality indicators between the patients cared for in stroke belt and non-stroke belt Veterans Affairs medical centers after risk adjustment. Conclusions These data suggest that a stroke belt does not exist within the Veterans Affairs health care system in terms of either post-admission mortality or inpatient care quality. C1 [Jia, Huanguang; Castro, Jaime; Vogel, W. Bruce] US Dept Vet Affairs, North Florida South Georgia Vet Hlth Syst, Rehabil Outcomes Res Ctr, Gainesville, FL 32608 USA. [Phipps, Michael] Yale Univ, Robert Wood Johnson Fdn, Sch Med, Clin Scholars Program, New Haven, CT USA. [Phipps, Michael] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. [Phipps, Michael] VA Connecticut Healthcare Syst, West Haven, CT USA. [Bravata, Dawn; Myers, Jennifer; Williams, Linda; Chumbler, Neale] Vet Affairs VA Hlth Serv Res & Dev HSR&D, Ctr Excellence Implementing Evidence Based Practi, Indianapolis, IN USA. [Bravata, Dawn; Myers, Jennifer; Williams, Linda; Chumbler, Neale] VA HSR&D Stroke Qual Enhancement Res Initiat Stro, Indianapolis, IN USA. [Bravata, Dawn; Williams, Linda; Chumbler, Neale] Regenstrief Inst Hlth Care, Indianapolis, IN USA. [Li, Xinli] VA Natl Surg Off, Denver, CO USA. [Ordin, Diana] US Dept Vet Affairs, Vet Hlth Adm, Off Analyt & Business Intelligence, Washington, DC USA. [Williams, Linda] Indiana Univ Sch Med, Dept Neurol, Indianapolis, IN 46202 USA. [Chumbler, Neale] Indiana Univ Purdue Univ, Indiana Univ Sch Liberal Arts, Dept Sociol, Indianapolis, IN 46202 USA. RP Jia, HG (reprint author), US Dept Vet Affairs, North Florida South Georgia Vet Hlth Syst, Rehabil Outcomes Res Ctr, 1601 SW Archer Rd, Gainesville, FL 32608 USA. EM huanguang.jia@va.gov FU Department of Veterans Affairs Health Services Research and Development (VA HSR D Grant) [RRP 09-184] FX This research was supported through the Department of Veterans Affairs Health Services Research and Development (VA HSR& D Grant RRP 09-184). The views and opinions expressed in this manuscript reflect those of the authors and do not necessarily reflect those of the Department of Veterans Affairs. NR 24 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD JAN PY 2015 VL 10 IS 1 BP 67 EP 72 DI 10.1111/j.1747-4949.2012.00861.x PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AW3AA UT WOS:000346156500020 PM 22974516 ER PT J AU Campbell, SN Zhang, C Monte, L Roe, AD Rice, KC Tache, Y Masliah, E Rissman, RA AF Campbell, Shannon N. Zhang, Cheng Monte, Louise Roe, Allyson D. Rice, Kenner C. Tache, Yvette Masliah, Eliezer Rissman, Robert A. TI Increased Tau Phosphorylation and Aggregation in the Hippocampus of Mice Overexpressing Corticotropin-Releasing Factor SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; corticotropin-releasing factor (CRF); corticotropin-releasing factor receptor (CRFR); electron microscopy; hippocampus; immunohistochemistry; stress; tau phosphorylation (tau-P); western blot ID COLD-WATER STRESS; ALZHEIMERS-DISEASE; NEUROFIBRILLARY TANGLES; TRANSGENIC MICE; CRF RECEPTORS; MOUSE-BRAIN; MICROTUBULE-BINDING; PROTEIN-TAU; FETAL-TAU; HYPERPHOSPHORYLATION AB Clinical and basic science research suggests that stress and/or changes in central stress signaling intermediates may be involved in Alzheimer's disease (AD) pathogenesis. Although the links between stress and AD remain unsettled, data from our group and others have established that stress exposure in rodents may confer susceptibility to AD pathology by inducing hippocampal tau phosphorylation (tau-P). Work in our laboratory has shown that stress-induced tau-P requires activation of the type-1 corticotropin-releasing factor receptor (CRFR1). CRF overexpressing (CRF-OE) mice are a model of chronic stress that display cognitive impairment at 9-10 month of age. In this study we used 6-7 month old CRF-OE mice to examine whether sustained exposure to CRF and stress steroids would impact hippocampal tau-P and kinase activity in the presence or absence of the CRFR1-specific antagonist, R121919, given daily for 30 days. CRF-OE mice had significantly elevated tau-P compared to wild type (WT) mice at the AT8 (S-202/T-204), PHF-1 (S-396/404), S-262, and S-422 sites. Treating CRF-OE mice with R121919 blocked phosphorylation at the AT8 (S-202/T-204) and PHF-1 (S-396/404) sites, but not at the S-262 and S-422 sites and reduced phosphorylation of c-Jun N Terminal Kinase (JNK). Examination of hippocampal extracts from CRF-OE mice at the ultrastructural level revealed negatively stained round/globular aggregates that were positively labeled by PHF-1. These data suggest critical roles for CRF and CRFR1 in tau-P and aggregation and may have implications for the development of AD cognitive decline. C1 [Campbell, Shannon N.; Zhang, Cheng; Monte, Louise; Roe, Allyson D.; Masliah, Eliezer; Rissman, Robert A.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Masliah, Eliezer] Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA. [Rice, Kenner C.] Natl Inst Drug Abuse, Chem Biol Res Branch, NIH, Bethesda, MD USA. [Tache, Yvette] NIAAA, Chem Biol Res Branch, NIH, Bethesda, MD USA. [Tache, Yvette] Univ Calif Los Angeles, Dept Med, Ctr Neurobiol Stress & Womens Hlth, Los Angeles, CA 90024 USA. [Tache, Yvette] Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Los Angeles, CA 90024 USA. [Tache, Yvette] Univ Calif Los Angeles, Ctr Neurobiol Stress, Div Digest Dis, Los Angeles, CA 90024 USA. VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. RP Rissman, RA (reprint author), UCSD, Sch Med, Dept Neurosci, 9500 Gilman Dr,MTF 314 M-C 0624, La Jolla, CA 92037 USA. EM rrissman@ucsd.edu FU NIA [AG032755]; Alzheimer's Art Quilt Initiative (AAQI); Alzheimer's Association; Shiley-Marcos Alzheimer's Disease Research Center at UCSD [AG005131]; Intramural Research Programs of the National Institute on Drug Abuse; National Institute on Alcohol Abuse and Alcoholism; Veteran Administration FX This work was supported by grants to RAR from NIA AG032755, the Alzheimer's Art Quilt Initiative (AAQI), the Alzheimer's Association and the Shiley-Marcos Alzheimer's Disease Research Center at UCSD (AG005131). The authors thank Drs. P. E. Sawchenko (Salk Inst) and L. Wang (UCLA) for helpful discussions. We also thank Dr. P. Davies for antibody PHF-1. A portion of this work was supported by the Intramural Research Programs of the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism. YT is in receipt of the senior Career Scientist Award from Veteran Administration. NR 67 TC 8 Z9 8 U1 0 U2 5 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 2015 VL 43 IS 3 BP 967 EP 976 DI 10.3233/JAD-141281 PG 10 WC Neurosciences SC Neurosciences & Neurology GA AU8PG UT WOS:000345858000024 PM 25125464 ER PT J AU Scheff, SW Price, DA Ansari, MA Roberts, KN Schmitt, FA Ikonomovic, MD Mufson, EJ AF Scheff, Stephen W. Price, Douglas A. Ansari, Mubeen A. Roberts, Kelly N. Schmitt, Frederick A. Ikonomovic, Milos D. Mufson, Elliott J. TI Synaptic Change in the Posterior Cingulate Gyrus in the Progression of Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; dementia; memory; mild cognitive impairment; synapses ID MILD COGNITIVE IMPAIRMENT; MITOCHONDRIAL CASCADE HYPOTHESIS; POSITRON-EMISSION-TOMOGRAPHY; AMYLOID-BETA-PEPTIDE; OXIDATIVE STRESS; A-BETA; ELDERLY SUBJECTS; NEUROPATHOLOGIC ASSESSMENT; ASSOCIATION GUIDELINES; PRESYNAPTIC PROTEINS AB Mild cognitive impairment (MCI) is considered to be an early stage in the progression of Alzheimer's disease (AD) providing an opportunity to investigate brain pathogenesis prior to the onset of dementia. Neuroimaging studies have identified the posterior cingulate gyrus (PostC) as a cortical region affected early in the onset of AD. This association cortex is involved in a variety of different cognitive tasks and is intimately connected with the hippocampal/entorhinal cortex region, a component of the medial temporal memory circuit that displays early AD pathology. We quantified the total number of synapses in lamina 3 of the PostC using unbiased stereology coupled with electron microscopy from short postmortem autopsy tissue harvested from cases at different stage of AD progression. Individuals in the early stages of AD showed a significant decline in synaptic numbers compared to individuals with no cognitive impairment (NCI). Subjects with MCI exhibited synaptic numbers that were between the AD and NCI cohorts. Adjacent tissue was evaluated for changes in both pre and postsynaptic proteins levels. Individuals with MCI demonstrated a significant loss in presynaptic markers synapsin-1 and synaptophysin and postsynaptic markers PSD-95 and SAP-97. Levels of [H-3]PiB binding was significantly increased in MCI and AD and correlated strongly with levels of synaptic proteins. All synaptic markers showed a significant association with Mini-Mental Status Examination scores. These results support the idea that the PostC synaptic function is affected during the prodromal stage of the disease and may underlie some of the early clinical sequelae associated with AD. C1 [Scheff, Stephen W.; Price, Douglas A.; Ansari, Mubeen A.; Roberts, Kelly N.; Schmitt, Frederick A.] Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. [Ikonomovic, Milos D.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Ikonomovic, Milos D.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Mufson, Elliott J.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. RP Scheff, SW (reprint author), Univ Kentucky, Ctr Aging, 101 Sanders Brown, Lexington, KY 40536 USA. EM sscheff@email.uky.edu FU National Institute of Health [AG028383, PO1AG014449, AG027219, AG042475, AG025204, AG043375]; Mansbach Chair in Alzheimer's Disease FX This work was supported by the National Institute of Health grants: AG028383, PO1AG014449, AG027219, AG042475, AG025204, and AG043375, and the Mansbach Chair in Alzheimer's Disease. We are indebted to the altruism of the participants in the Sanders-Brown Center on Aging and the Religious Orders Study (P30AG10161). NR 140 TC 20 Z9 20 U1 1 U2 7 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 2015 VL 43 IS 3 BP 1073 EP 1090 DI 10.3233/JAD-141518 PG 18 WC Neurosciences SC Neurosciences & Neurology GA AU8PG UT WOS:000345858000032 PM 25147118 ER PT J AU Delaney, M Ballen, KK AF Delaney, Meghan Ballen, Karen K. TI Umbilical Cord Blood Transplantation: Review of Factors Affecting the Hospitalized Patient SO JOURNAL OF INTENSIVE CARE MEDICINE LA English DT Article DE cord blood; hematopoietic stem cell transplantation ID STEM-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; ACUTE LUNG INJURY; PROPHYLACTIC PLATELET TRANSFUSION; HEPATIC VENOOCCLUSIVE DISEASE; REVERSIBLE ENCEPHALOPATHY SYNDROME; UNRELATED DONOR; ACUTE-LEUKEMIA; PERIPHERAL-BLOOD AB The use of umbilical cord blood (UCB) as a stem cell donor source has dramatically increased over the last 2 decades. Patients undergoing UCB transplantation share medical management issues with patients receiving a hematopoietic stem cell transplantion using adult donor sources (peripheral blood stem cells or bone marrow stem cells) and may also have more complex medical issues that appear to be related to delayed immune recovery from UCB-derived stem cells. The interface with critical care providers is likely to occur in the transplant and posttransplant setting. Patients may experience UCB infusion reactions that range from mild to rarely severe. Following transplant, patients are transfusion dependent for long periods due to the prolonged engraftment of UCB cells. They are at high risk of infection, particularly viral. Once engrafted, UCB transplant patients have a lower rate of graft versus host disease compared to other donor sources. Some of the other complications that are seen in patients undergoing UCB transplant are posttransplant lymphoproliferative disease, diffuse alveolar hemorrhage, and posterior reversible encephalopathy will also be discussed. C1 [Delaney, Meghan] Puget Sound Blood Ctr, Seattle, WA 98104 USA. [Delaney, Meghan] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Ballen, Karen K.] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. RP Delaney, M (reprint author), Puget Sound Blood Ctr, 921 Terry Ave, Seattle, WA 98104 USA. EM meghand@psbc.org NR 106 TC 0 Z9 0 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0885-0666 EI 1525-1489 J9 J INTENSIVE CARE MED JI J. Intensive Care Med. PD JAN PY 2015 VL 30 IS 1 BP 13 EP 22 DI 10.1177/0885066613488730 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA AW3LD UT WOS:000346187300003 PM 23753249 ER PT J AU Solimeo, SL Ono, SS Lampman, MAM Paez, MBW Stewart, GL AF Solimeo, Samantha L. Ono, Sarah S. Lampman, Michelle A. M. Paez, Monica B. W. Stewart, Gregory L. TI The empowerment paradox as a central challenge to patient centered medical home implementation in the veteran's health administration SO JOURNAL OF INTERPROFESSIONAL CARE LA English DT Article DE Health and social care; interprofessional collaboration; mixed methods; patient centered practice; professional identity; team-based care ID PRIMARY-CARE; INTERPROFESSIONAL EDUCATION; ROLE-CONFLICT; ROLE STRESS; TEAMS; WORK; ANTECEDENTS; ENGAGEMENT; AMBIGUITY; BURNOUT AB In this paper we present results of a mixed methods study conducted to identify barriers to team function among staff implementing patient aligned care teams - the Department of Veterans Affairs' patient centered medical home (PCMH) model. Using a convergent mixed methods design, we administered a standardized survey measure (Team and Individual Role Perception Survey) to assess work role challenge and engagement; and conducted discussion groups to gather context pertaining to role change. We found that the role of primary care providers is highly challenging and did not become less difficult over the initial year of implementation. Unexpectedly over the course of the first year nurse care managers reported a decrease in their perceptions of empowerment and clerical associates reported less skill variety. Qualitative data suggest that more skilled team members fail to delegate and share tasks within their teams. We characterize this interprofessional knowledge factor as an empowerment paradox where team members find it difficult to share tasks in ways that are counter to traditionally structured hierarchical roles. Health care systems seeking to implement PCMH should dedicate resources to facilitating within-team role knowledge and negotiation. C1 [Solimeo, Samantha L.; Ono, Sarah S.; Lampman, Michelle A. M.; Paez, Monica B. W.; Stewart, Gregory L.] US Dept Vet Affairs, VISN Patient Aligned Care Team Demonstrat Lab 23, Iowa City, IA USA. [Solimeo, Samantha L.; Ono, Sarah S.; Paez, Monica B. W.] US Dept Vet Affairs, Ctr Comprehens Access & Delivery Res & Evaluat, Iowa City, IA USA. [Ono, Sarah S.] US Dept Vet Affairs, Off Rural Hlth Cent Reg, Iowa City, IA USA. [Stewart, Gregory L.] Univ Iowa, Henry B Tippie Coll Business, Iowa City, IA USA. RP Solimeo, SL (reprint author), Iowa City VA Hlth Care Syst, Dept Vet Affairs, VISN Patient Aligned Care Team Demonstrat Lab 23, 601 Highway 6 West, Iowa City, IA 52246 USA. EM Samantha.Solimeo@va.gov FU VISN 23 Patient Aligned Care Team Demonstration Lab - VA Office of Patient Care Services; Center for Comprehensive Access & Delivery Research and Evaluation - VA Health Services Research and Development Service FX The authors report no declarations of interest. The authors arc responsible for the writing and content of this paper. This study was supported by the VISN 23 Patient Aligned Care Team Demonstration Lab, funded by the VA Office of Patient Care Services. Additional support was provided by the Center for Comprehensive Access & Delivery Research and Evaluation, funded by the VA Health Services Research and Development Service. None of these sponsors had any role in the study design, methods, analyses, or interpretation or in the preparation of the manuscript and the decision to submit it for publication. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. NR 35 TC 5 Z9 5 U1 1 U2 17 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1356-1820 EI 1469-9567 J9 J INTERPROF CARE JI J. Interprofessional Care PD JAN PY 2015 VL 29 IS 1 BP 26 EP 33 DI 10.3109/13561820.2014.937480 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AW1WU UT WOS:000346080000006 PM 25052920 ER PT J AU Stein, BD Gordon, AJ Dick, AW Burns, RM Pacula, RL Farmer, CM Leslie, DL Sorbero, M AF Stein, Bradley D. Gordon, Adam J. Dick, Andrew W. Burns, Rachel M. Pacula, Rosalie Liccardo Farmer, Carrie M. Leslie, Douglas L. Sorbero, Mark TI Supply of buprenorphine waivered physicians: The influence of state policies SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE Opioid use disorder; Buprenorphine; Medication assisted treatment; Medicaid; State policy ID OFFICE-BASED TREATMENT; OPIOID ADDICTION TREATMENT; 1ST 3 YEARS; METHADONE-MAINTENANCE; COST-EFFECTIVENESS; HEROIN DEPENDENCE; OPIATE ADDICTION; RANDOMIZED-TRIAL; UNITED-STATES; CARE AB Buprenorphine, an effective opioid use disorder treatment, can be prescribed only by buprenorphine-waivered physicians. We calculated the number of buprenorphine-waivered physicians/100,000 county residents using 2008-11 Buprenorphine Waiver Notification System data, and used multivariate regression models to predict number of buprenorphine-waivered physicians/100,000 residents in a county as a function of county characteristics, state policies and efforts to promote buprenorphine use. In 2011, 43% of US counties had no buprenorphine-waivered physicians and 7% had 20 or more waivered physicians. Medicaid funding, opioid overdose deaths, and specific state guidance for office-based buprenorphine use were associated with more buprenorphine-waivered physicians, while encouraging methadone programs to promote buprenorphine use had no impact. Our findings provide important empirical information to individuals seeking to identify effective approaches to increase the number of physicians able to prescribe buprenorphine. (C) 2014 Elsevier Inc. All rights reserved. C1 [Stein, Bradley D.; Dick, Andrew W.; Burns, Rachel M.; Pacula, Rosalie Liccardo; Farmer, Carrie M.; Sorbero, Mark] RAND Corp, Pittsburgh, PA 15219 USA. [Stein, Bradley D.; Gordon, Adam J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15261 USA. [Leslie, Douglas L.] Penn State Coll Med, Hershey, PA 17033 USA. RP Stein, BD (reprint author), RAND Corp, 4570 Fifth Ave, Pittsburgh, PA 15219 USA. EM stein@rand.org FU NIDA NIH HHS [R01 DA032881, R01DA032881-01A1] NR 77 TC 19 Z9 19 U1 5 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD JAN PY 2015 VL 48 IS 1 SI SI BP 104 EP 111 DI 10.1016/j.jsat.2014.07.010 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA AW3ZL UT WOS:000346221400016 PM 25218919 ER PT J AU Rosell, DR Zaluda, LC McClure, MM Perez-Rodriguez, MM Strike, KS Barch, DM Harvey, PD Girgis, RR Hazlett, EA Mailman, RB Abi-Dargham, A Lieberman, JA Siever, LJ AF Rosell, Daniel R. Zaluda, Lauren C. McClure, Margaret M. Perez-Rodriguez, M. Mercedes Strike, K. Sloan Barch, Deanna M. Harvey, Philip D. Girgis, Ragy R. Hazlett, Erin A. Mailman, Richard B. Abi-Dargham, Anissa Lieberman, Jeffrey A. Siever, Larry J. TI Effects of the D-1 Dopamine Receptor Agonist Dihydrexidine (DAR-0100A) on Working Memory in Schizotypal Personality Disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Article ID FUNCTIONAL SELECTIVITY; SCHIZOPHRENIA SPECTRUM; NEUROPSYCHOLOGICAL PERFORMANCE; COGNITIVE PERFORMANCE; HIGH-POTENCY; D1; EFFICACY; AMPHETAMINE; RATS; SPECIFICITY AB Pharmacological enhancement of prefrontal D-1 dopamine receptor function remains a promising therapeutic approach to ameliorate schizophrenia-spectrum working memory deficits, but has yet to be rigorously evaluated clinically. This proof-of-principle study sought to determine whether the active enantiomer of the selective and full D-1 receptor agonist dihydrexidine (DAR-0100A) could attenuate working memory impairments in unmedicated patients with schizotypal personality disorder (SPD). We performed a randomized, double-blind, placebo-controlled trial of DAR-0100A (15 mg/150 ml of normal saline administered intravenously over 30 min) in medication-free patients with SPD (n = 16) who met the criteria for cognitive impairment (ie, scoring below the 25th percentile on tests of working memory). We employed two measures of verbal working memory that are salient to schizophrenia-spectrum cognitive deficits, and that clinical data implicate as being associated with prefrontal D-1 availability: (1) the Paced Auditory Serial Addition Test (PASAT); and (2) the N-back test (ratio of 2-back: 0-back scores). Study procedures occurred over four consecutive days, with working memory testing on Days 1 and 4, and DAR-0100A/placebo administration on Days 2-4. Treatment with DAR-0100A was associated with significantly improved PASAT performance relative to placebo, with a very large effect size (Cohen's d = 1.14). Performance on the N-back ratio was also significantly improved; however, this effect rested on both a non-significant enhancement and diminution of 2-back and 0-back performance, respectively; therefore interpretation of this finding is more complicated. DAR-0100A was generally well tolerated, with no serious medical or psychiatric adverse events; common side effects were mild to moderate and transient, consisting mainly of sedation, lightheadedness, tachycardia, and hypotension; however, we were able to minimize these effects, without altering the dose, with supportive measures, eg, co-administered normal saline. Although preliminary, these findings lend further clinical support to the potential of D-1 receptor agonists to treat schizophrenia-spectrum working memory impairments. These data suggest a need for further studies with larger group sizes, serum DAR-0100A levels, and a more comprehensive neuropsychological battery. C1 [Rosell, Daniel R.; Zaluda, Lauren C.; McClure, Margaret M.; Perez-Rodriguez, M. Mercedes; Strike, K. Sloan; Hazlett, Erin A.; Siever, Larry J.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Rosell, Daniel R.] James J Peters VA Med Ctr, Dept Outpatient Psychiat, Bronx, NY USA. [Zaluda, Lauren C.; McClure, Margaret M.; Perez-Rodriguez, M. Mercedes; Strike, K. Sloan; Hazlett, Erin A.; Siever, Larry J.] James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr MIRECC VISN 3, Bronx, NY USA. [Barch, Deanna M.] Washington Univ, Dept Psychol, St Louis, MO 63130 USA. [Harvey, Philip D.] Univ Miami, Miller Sch Med, Dept Psychiat, Miami, FL 33136 USA. [Harvey, Philip D.] Bruce W Carter VA Med Ctr, Res Serv, Miami, FL USA. [Girgis, Ragy R.; Abi-Dargham, Anissa; Lieberman, Jeffrey A.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Girgis, Ragy R.; Abi-Dargham, Anissa; Lieberman, Jeffrey A.] Columbia Univ, Dept Psychiat, Med Ctr, New York, NY USA. [Mailman, Richard B.] Penn State Univ, Dept Pharmacol, Coll Med, Hershey, PA USA. RP Siever, LJ (reprint author), Vet Affairs Med Ctr, James J Peters Dept, 130 West Kingsbridge Rd,Room 6A-44, Bronx, NY 10468 USA. EM larry.siever@va.gov RI Perez Rodriguez, Maria/B-9410-2013; Girgis, Ragy/N-3271-2016; OI Perez Rodriguez, Maria/0000-0001-5137-1993; Mailman, Richard/0000-0003-1353-2738 FU Veterans Affairs VISN3 Mental Illness Research, Education, and Clinical Center; Department of Veterans Affairs Office of Academic Affiliations Psychiatric Research/Neurosciences Advanced Fellowship; National Center for Research Resources (NCRR) [MO1-RR-00071]; National Institutes of Health (NIH) FX We thank Drs Luis Ripoll and Amir Garakani for medical assistance; Dr Katherine Burdick for statistical consultation; and Nabila Hoque for technical assistance. This work was supported by the Veterans Affairs VISN3 Mental Illness Research, Education, and Clinical Center. Writing of this manuscript was supported by The Department of Veterans Affairs Office of Academic Affiliations Psychiatric Research/Neurosciences Advanced Fellowship. This publication was made possible by Grant Number MO1-RR-00071 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). NR 48 TC 10 Z9 11 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2015 VL 40 IS 2 BP 446 EP 453 DI 10.1038/npp.2014.192 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AW2WQ UT WOS:000346147800021 PM 25074637 ER PT J AU Cravero, JP Cote, CJ AF Cravero, Joseph P. Cote, Charles J. TI Raising the bar for pediatric sedation studies and trials SO PEDIATRIC ANESTHESIA LA English DT Editorial Material ID ADVERSE EVENTS; CHILDREN; DEXMEDETOMIDINE; ANESTHESIA; MRI; PROPOFOL C1 [Cravero, Joseph P.] Boston Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Cote, Charles J.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Cravero, JP (reprint author), Boston Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. EM Joseph.cravero@childrens.harvard.edu NR 9 TC 3 Z9 3 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1155-5645 EI 1460-9592 J9 PEDIATR ANESTH JI Pediatr. Anesth. PD JAN PY 2015 VL 25 IS 1 SI SI BP 2 EP 4 DI 10.1111/pan.12532 PG 3 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA AW3BZ UT WOS:000346161800002 PM 25483270 ER PT J AU Patterson, BJ Solimeo, SL Stewart, KR Rosenthal, GE Kaboli, PJ Lund, BC AF Patterson, Brandon J. Solimeo, Samantha L. Stewart, Kenda R. Rosenthal, Gary E. Kaboli, Peter J. Lund, Brian C. TI Perceptions of pharmacists' integration into patient-centered medical home teams SO RESEARCH IN SOCIAL & ADMINISTRATIVE PHARMACY LA English DT Article DE Patient-centered medical home; Pharmacy services; Veteran affairs; Health care teams ID HEALTH-CARE TEAM; THERAPY MANAGEMENT; PHYSICIANS PERCEPTIONS; COMMUNITY PHARMACISTS; GENERAL-PRACTITIONERS; CLINICAL PHARMACISTS; QUALITATIVE-ANALYSIS; FAMILY-PRACTICE; SERVICES; EXPECTATIONS AB Background: Patient-centered medical homes (PCMHs) are a newer paradigm of health care service delivery. Team-based care that includes pharmacists has been implemented in several countries. Subsequently studies have successfully identified challenges and barriers with team-based care. Research on pharmacists' integration into PCMH is warranted to help bridge knowledge from earlier studies exploring team-based care. In 2010, the Department of Veteran Affairs (VA) began a national PCMH implementation, operationalized as "Patient-Aligned Care Teams" (PACTs). The VA's national PACT implementation presents an opportunity to describe other persistent barriers to effective coordination between primary care and pharmacy providers. Objective: To identify perceived barriers and facilitators to pharmacist integration into VA PACTs from the perspective of non-pharmacist team members. Methods: Semi-structured interviews were conducted as part of a formative evaluation of PCMH implementation. Participants were from VA medical centers and community-based outpatient clinics in the Midwestern United States and included physicians, nurses, associated health care professionals, and health system administrators. Results: In working toward pharmacy service integration, role clarity and work activities were influenced by team member attitudes toward and previous experiences with pharmacists. Interviewees reported that coordination with pharmacists was hindered if communication placed extra burdens on other team members. Interviewees reported collaboration was easier when pharmacists were onsite, but that technology helped facilitate off-site access to pharmacy services. Finally, some team members characterized pharmacist integration as essential while others failed to integrate pharmacists at all. Conclusion: Non-pharmacist members of PACT teams reported some reluctance in pharmacists' integration. They attributed this reluctance to knowledge deficits, limited participation in PACT training by pharmacists, an imbalance in effort expended for pharmacists' integration, and coordination or communication challenges. While there may be unique opportunities for pharmacists to improve patient care through participation in PCMHs, work remains to improve other health professionals' knowledge of and attitudes toward pharmacists' roles on health care teams. (C) 2015 Elsevier Inc. All rights reserved. C1 [Patterson, Brandon J.] Univ Sci, Philadelphia Coll Pharm, Philadelphia, PA 19104 USA. [Solimeo, Samantha L.; Stewart, Kenda R.; Rosenthal, Gary E.] US Dept Vet Affairs, VISN Patient Aligned Care Team 23, Demonstrat Lab, Iowa City, VA USA. [Stewart, Kenda R.; Rosenthal, Gary E.; Kaboli, Peter J.; Lund, Brian C.] US Dept Vet Affairs, Ctr Comprehens Access & Delivery Res & Evaluat, Iowa City, VA USA. [Solimeo, Samantha L.; Stewart, Kenda R.; Kaboli, Peter J.; Lund, Brian C.] US Dept Vet Affairs, Vet Rural Hlth Resource Ctr Cent Reg, Iowa City, IA 52246 USA. [Rosenthal, Gary E.; Kaboli, Peter J.] Univ Iowa, Coll Med, Iowa City, IA 52242 USA. [Rosenthal, Gary E.; Lund, Brian C.] Univ Iowa, Coll Publ Hlth, Iowa City, IA 52242 USA. RP Lund, BC (reprint author), Iowa City Vet Affairs Hlth Care Syst, Mailstop 152,601 Hwy 6 W, Iowa City, IA 52246 USA. EM brian.lund@va.gov NR 62 TC 7 Z9 7 U1 5 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7411 EI 1934-8150 J9 RES SOC ADMIN PHARM JI Res. Soc. Adm. Pharm. PD JAN-FEB PY 2015 VL 11 IS 1 BP 85 EP 95 DI 10.1016/j.sapharm.2014.05.005 PG 11 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AW1MB UT WOS:000346052400008 PM 24954185 ER PT J AU Gutnik, L Dieleman, J Dare, AJ Shrime, MG Yamey, G AF Gutnik, L. Dieleman, J. Dare, A. J. Shrime, Mark G. Yamey, Gavin TI Funding allocation to surgery in low and middle-income countries: a retrospective analysis of contributions from the USA (vol 5, e008780, 2015) SO BMJ OPEN LA English DT Correction C1 [Shrime, Mark G.] Massachusetts Eye & Ear Infirm, Off Global Surg, Boston, MA 02114 USA. [Shrime, Mark G.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Yamey, Gavin] Duke Univ, Duke Global Hlth Inst, Durham, NC USA. NR 1 TC 3 Z9 3 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2015 VL 5 IS 11 AR e008780 DI 10.1136/bmjopen-2015-008780corr1 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA DB9MK UT WOS:000368840100032 ER PT J AU Gutnik, L Dieleman, J Dare, AJ Ramos, MS Riviello, R Meara, JG Yamey, G Shrime, MG AF Gutnik, Lily Dieleman, Joseph Dare, Anna J. Ramos, Margarita S. Riviello, Robert Meara, John G. Yamey, Gavin Shrime, Mark G. TI Funding allocation to surgery in low and middle-income countries: a retrospective analysis of contributions from the USA SO BMJ OPEN LA English DT Article ID GLOBAL HEALTH; COST-EFFECTIVENESS; ANESTHESIA INFRASTRUCTURE; DEVELOPMENT ASSISTANCE; HOSPITALS; CAPACITY; DISEASE; BURDEN AB Objective: The funds available for global surgical delivery, capacity building and research are unknown and presumed to be low. Meanwhile, conditions amenable to surgery are estimated to account for nearly 30% of the global burden of disease. We describe funds given to these efforts from the USA, the world's largest donor nation. Design: Retrospective database review. US Agency for International Development (USAID), National Institute of Health (NIH), Foundation Center and registered US charitable organisations were searched for financial data on any organisation giving exclusively to surgical care in low and middle income countries (LMICs). For USAID, NIH and Foundation Center all available data for all years were included. The five recent years of financial data per charitable organisation were included. All nominal dollars were adjusted for inflation by converting to 2014 US dollars. Setting: USA. Participants: USAID, NIH, Foundation Center, Charitable Organisations. Primary and secondary outcome measures: Cumulative funds appropriated to global surgery. Results: 22 NIH funded projects (totalling $31.3 million) were identified, primarily related to injury and trauma. Six relevant USAID projects were identified-all obstetric fistula care totalling $438 million. A total of $105 million was given to universities and charitable organisations by US foundations for 12 different surgical specialties. 95 US charitable organisations representing 14 specialties totalled revenue of $2.67 billion and expenditure of $2.5 billion. Conclusions and relevance: Current funding flows to surgical care in LMICs are poorly understood. US funding predominantly comes from private charitable organisations, is often narrowly focused and does not always reflect local needs or support capacity building. Improving surgical care, and embedding it within national health systems in LMICs, will likely require greater financial investment. Tracking funds targeting surgery helps to quantify and clarify current investments and funding gaps, ensures resources materialise from promises and promotes transparency within global health financing. C1 [Gutnik, Lily] Montefiore Med Ctr, Dept Surg, 111 E 210th St, Bronx, NY 10467 USA. [Gutnik, Lily; Ramos, Margarita S.; Riviello, Robert] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Gutnik, Lily] UNC Project Malawi, Lilongwe, Malawi. [Dieleman, Joseph] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA. [Dare, Anna J.] Kings Hlth Partners, Kings Ctr Global Hlth, Dept Global Hlth, London, England. [Dare, Anna J.] Kings Coll London, London, England. [Riviello, Robert; Meara, John G.] Harvard Univ, Sch Med, Program Global Surg & Social Change, Boston, MA USA. [Meara, John G.] Boston Childrens Hosp, Boston, MA USA. [Yamey, Gavin] Duke Univ, Duke Global Hlth Inst, Durham, NC USA. [Shrime, Mark G.] Massachusetts Eye & Ear Infirm, Office Global Surg, Boston, MA 02114 USA. [Shrime, Mark G.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Gutnik, L (reprint author), Montefiore Med Ctr, Dept Surg, 111 E 210th St, Bronx, NY 10467 USA. EM Lily.gutnik@mail.harvard.edu NR 23 TC 3 Z9 3 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2015 VL 5 IS 11 DI 10.1136/bmjopen-2015-008780 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA DB9MK UT WOS:000368840100054 ER PT J AU Kotova, S Wong, RM Cameron, RB AF Kotova, Svetlana Wong, Raymond M. Cameron, Robert B. TI New and emerging therapeutic options for malignant pleural mesothelioma: review of early clinical trials SO CANCER MANAGEMENT AND RESEARCH LA English DT Review DE MPM; new targeted; systemic; local therapies AB Malignant pleural mesothelioma (MPM) is a rare tumor that is challenging to control. Despite some benefit from using the multimodality-approach (surgery, combination chemotherapy and radiation), survival remains poor. However, current research produced a list of potential therapies. Here, we summarize significant new preclinical and early clinical developments in treatment of MPM, which include mesothelin specific antibody and toxin therapies, interleukin-4 (IL-4) receptor toxins, dendritic cell vaccines, immune checkpoint inhibitors, and gene-based therapies. In addition, several local modalities such as photodynamic therapy, postoperative lavage using betadine, and cryotherapy for local recurrence, have also shown to be effective for local control of disease. C1 [Kotova, Svetlana; Wong, Raymond M.; Cameron, Robert B.] Vet Affairs Greater Los Angeles Healthcare Syst, Div Thorac Surg, Los Angeles, CA USA. [Kotova, Svetlana; Wong, Raymond M.; Cameron, Robert B.] Univ Calif Los Angeles, Div Thorac Surg, Los Angeles, CA USA. [Kotova, Svetlana; Wong, Raymond M.; Cameron, Robert B.] Comprehens Mesothelioma Program, Los Angeles, CA USA. [Wong, Raymond M.] Pacific Heart Lung & Blood Inst, Pacific Meso Ctr, Los Angeles, CA USA. RP Cameron, RB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Thorac Surg, Ctr Hlth Sci, 10833 Le Conte Ave,Room 64-128,POB 957313, Los Angeles, CA 90095 USA. EM skotova@mednet.ucla.edu; rcameron@mednet.ucla.edu NR 100 TC 9 Z9 9 U1 0 U2 4 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1179-1322 J9 CANCER MANAG RES JI Cancer Manag. Res. PY 2015 VL 7 BP 51 EP 63 DI 10.2147/CMAR.S72814 PG 13 WC Oncology SC Oncology GA V46LK UT WOS:000209885500006 PM 25670913 ER PT J AU Svensson, E Lash, TL Resick, PA Hansen, JG Gradus, JL AF Svensson, Elisabeth Lash, Timothy L. Resick, Patricia A. Hansen, Jens Georg Gradus, Jaimie L. TI Validity of reaction to severe stress and adjustment disorder diagnoses in the Danish Psychiatric Central Research Registry SO CLINICAL EPIDEMIOLOGY LA English DT Article DE validity (epidemiology); stress disorders; traumatic; Denmark AB Aims: To assess the validity of reaction to severe stress and adjustment disorder diagnoses registered in the Danish Psychiatric Central Research Register (DPCRR), to examine the documentation of stressful and traumatic events in the medical records, and to investigate the occurrence of stress diagnoses among persons not registered in the DPCRR. Methods: Among 101,633 patients diagnosed with International Classification of Diseases, 10th Edition (ICD-10) F43 diagnoses between 1995 and 2011, we selected 50 patients from two hospitals (100 total), comprising one above and one below median age for each diagnosis for five time periods, and reviewed their medical records. We calculated the positive predictive value, comparing registration in the DPCRR with the original medical records, and captured data on stressful life events. Two general practitioners were queried about 50 patients without a stress diagnosis in the DPCRR, regarding whether they had ever received a stress diagnosis. Results: The positive predictive value was 58% for acute stress reaction, 83% for posttraumatic stress disorder, 94% for adjustment disorder, 71% for other reactions to severe stress, and 68% for reaction to severe stress, unspecified. In 80% of the records, a stressful or traumatic event was noted. Of 100 patients without an F43 diagnosis in the DPCRR, seven had a stress diagnosis. Conclusion: The DPCRR represents a valid and comprehensive resource for research on reaction to severe stress and adjustment disorders, particularly for posttraumatic stress disorder and adjustment disorder. C1 [Svensson, Elisabeth; Lash, Timothy L.; Hansen, Jens Georg] Aarhus Univ Hosp, Inst Clin Med, Dept Clin Epidemiol, Aarhus, Denmark. [Lash, Timothy L.] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA. [Resick, Patricia A.] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. [Gradus, Jaimie L.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Gradus, Jaimie L.] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. [Gradus, Jaimie L.] Boston Univ, Dept Epidemiol, Boston, MA 02215 USA. RP Svensson, E (reprint author), Aarhus Univ Hosp, Dept Clin Epidemiol, Olof Palmes Alle 43-45, DK-8200 Aarhus N, Denmark. EM elisabeth.svensson@clin.au.dk OI Svensson, Elisabeth/0000-0001-6706-6336 FU National Institute of Mental Health [1R21MH094551-01A1] FX The authors acknowledge the assistance of medical secretaries at the two hospitals, and the two general practitioners for their thorough evaluation of records. This work was funded by a National Institute of Mental Health grant: "Constructing a Danish Reaction to Severe Stress Cohort" (1R21MH094551-01A1), Jaimie Gradus, Principal Investigator. NR 19 TC 7 Z9 7 U1 0 U2 4 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1179-1349 J9 CLIN EPIDEMIOL JI Clin. Epidemiol. PY 2015 VL 7 BP 235 EP 242 DI 10.2147/CLEP.S80514 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V46UY UT WOS:000209910300025 PM 25870515 ER PT J AU Guizzetti, M Zhang, X Goeke, C Gavin, DP AF Guizzetti, Marina Zhang, Xiaolu Goeke, Calla Gavin, David P. TI Gila and neurodevelopment. focus on fetal alcohol spectrum disorders (vol 2, 123, 2014) SO FRONTIERS IN PEDIATRICS LA English DT Correction DE fetal alcohol spectrum disorders; glia; astrocytes; microglia; oligodendrocytes 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), Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. EM guizzett@ohsu.edu FU National Institute of Alcoholism and Alcohol Abuse, Department of Veterans Affairs [AA021876, 101BX001819, IK2BX001650] FX This study was supported in part by grant AA021876 from the National Institute of Alcoholism and Alcohol Abuse, Department of Veterans Affairs Merit Review Awards #101BX001819 (MG) and Career Development Award (CDA-2) #IK2BX001650 (DG). The authors are extremely grateful to Mr. Jeff Frkonja for the graphic design of Figures 1, 3, and 4. 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 2015 VL 3 AR 27 DI 10.3389/fped.2015.00027 PG 1 WC Pediatrics SC Pediatrics GA V46PZ UT WOS:000209897400025 PM 25954735 ER PT J AU Valencia, CA Husami, A Holle, J Johnson, JA Qian, YP Mathur, A Wei, C Indugula, SR Zou, FG Meng, HY Wang, LJ Li, X Fisher, R Tan, T Begtrup, AH Collins, K Wusik, KA Neilson, D Burrow, T Schorry, E Hopkin, R Keddache, M Harley, JB Kaufman, KM Zhang, KJ AF Valencia, C. Alexander Husami, Ammar Holle, Jennifer Johnson, Judith A. Qian, Yaping Mathur, Abhinav Wei, Chao Indugula, Subba Rao Zou, Fanggeng Meng, Haiying Wang, Lijun Li, Xia Fisher, Rachel Tan, Tony Begtrup, Amber Hogart Collins, Kathleen Wusik, Katie A. Neilson, Derek Burrow, Thomas Schorry, Elizabeth Hopkin, Robert Keddache, Mehdi Harley, John Barker Kaufman, Kenneth M. Zhang, Kejian TI Clinical impact and cost-effectiveness of whole exome sequencing as a diagnostic tool: a pediatric center's experience SO FRONTIERS IN PEDIATRICS LA English DT Article DE whole exome sequencing; next generation sequencing; diagnosis; children; clinical utility; pediatrics AB Background: There are limited reports of the use of whole exome sequencing (WES) as a clinical diagnostic tool. Moreover, there are no reports addressing the cost burden associated with genetic tests performed prior to WES. Objective: We demonstrate the performance characteristics of WES in a pediatric setting by describing our patient cohort, calculating the diagnostic yield, and detailing the patients for whom clinical management was altered. Moreover, we examined the potential cost-effectiveness of WES by examining the cost burden of diagnostic workups. Methods: To determine the clinical utility of our hospital's clinical WES, we performed a retrospective review of the first 40 cases. We utilized dual bioinformatics analyses pipelines based on commercially available software and in-house tools. Results: Of the first 40 clinical cases, we identified genetic defects in 12 (30%) patients, of which 47% of the mutations were previously unreported in the literature. Among the 12 patients with positive findings, seven have autosomal dominant disease and five have autosomal recessive disease. Ninety percent of the cohort opted to receive secondary findings and of those, secondary medical actionable results were returned in three cases. Among these positive cases, there are a number of novel mutations that are being reported here. The diagnostic workup included a significant number of genetic tests with microarray and single-gene sequencing being the most popular tests. Significantly, genetic diagnosis from WES led to altered patient medical management in positive cases. Conclusion: We demonstrate the clinical utility of WES by establishing the clinical diagnostic rate and its impact on medical management in a large pediatric center. The cost-effectiveness of WES was demonstrated by ending the diagnostic odyssey in positive cases. Also, in some cases it may be most cost-effective to directly perform WES. WES provides a unique glimpse into the complexity of genetic disorders. C1 [Valencia, C. Alexander; Husami, Ammar; Holle, Jennifer; Johnson, Judith A.; Mathur, Abhinav; Wei, Chao; Indugula, Subba Rao; Zou, Fanggeng; Meng, Haiying; Wang, Lijun; Li, Xia; Fisher, Rachel; Tan, Tony; Begtrup, Amber Hogart; Collins, Kathleen; Wusik, Katie A.; Neilson, Derek; Burrow, Thomas; Schorry, Elizabeth; Hopkin, Robert; Keddache, Mehdi; Zhang, Kejian] Cincinnati Childrens Hosp Med Ctr, Div Human Genet, 3333 Burnet Ave,MLC7016, Cincinnati, OH 45229 USA. [Valencia, C. Alexander; Husami, Ammar; Holle, Jennifer; Johnson, Judith A.; Mathur, Abhinav; Wei, Chao; Indugula, Subba Rao; Zou, Fanggeng; Meng, Haiying; Wang, Lijun; Li, Xia; Fisher, Rachel; Tan, Tony; Begtrup, Amber Hogart; Collins, Kathleen; Wusik, Katie A.; Neilson, Derek; Burrow, Thomas; Schorry, Elizabeth; Hopkin, Robert; Keddache, Mehdi; Harley, John Barker; Kaufman, Kenneth M.; Zhang, Kejian] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA. [Qian, Yaping] Myriad Genet Labs Inc, Salt Lake City, UT USA. [Harley, John Barker; Kaufman, Kenneth M.] Cincinnati Childrens Hosp Med Ctr, CAGE, Cincinnati, OH 45229 USA. [Harley, John Barker; Kaufman, Kenneth M.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. RP Valencia, CA (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Human Genet, 3333 Burnet Ave,MLC7016, Cincinnati, OH 45229 USA. EM alexander.valencia@cchmc.org FU National Human Genome Research Institute [U01 HG006828] FX JH and KK are partially supported by the National Human Genome Research Institute (U01 HG006828). NR 55 TC 11 Z9 11 U1 1 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 2015 VL 3 AR 67 DI 10.3389/fped.2015.00067 PG 15 WC Pediatrics SC Pediatrics GA V46PZ UT WOS:000209897400065 PM 26284228 ER PT S AU Nappi, JJ Hironaka, T Regge, D Yoshida, H AF Naeppi, Janne J. Hironaka, Toru Regge, Daniele Yoshida, Hiroyuki BE Tourassi, GD Armato, SG TI Deep transfer learning of virtual endoluminal views for the detection of polyps in CT colonography SO MEDICAL IMAGING 2016: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Computer-Aided Diagnosis CY FEB 28-MAR 02, 2016 CL San Diego, CA SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, ImXPAD DE Deep learning; colon and other gastrointestinal tract; transfer learning; deep convolutional neural network; CT colonography; false-positive reduction; detection; computer-aided detection ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; COLORECTAL-CANCER; OPTICAL COLONOSCOPY; LOCALIZATION; SURVEILLANCE; NEOPLASIA; TIME AB Proper training of deep convolutional neural networks (DCNNs) requires large annotated image databases that are currently not available in CT colonography (CTC). In this study, we employed a deep transfer learning (DETALE) scheme to circumvent this problem in automated polyp detection for CTC. In our method, a DCNN that had been pre-trained with millions of non-medical images was adapted to identify polyps using virtual endoluminal images of the polyp candidates prompted by a computer-aided detection (CADe) system. For evaluation, 154 CTC cases with and without fecal tagging were divided randomly into a development set and an external validation set including 107 polyps >= 6 mm in size. A CADe system was trained to detect polyp candidates using the development set, and the virtual endoluminal images of the polyp candidates were labeled manually into true-positive and several false-positive (FP) categories for transfer learning of the DCNN. Next, the trained CADe system was used to detect polyp candidates from the external validation set, and the DCNN reviewed their images to determine the final detections. The detection sensitivity of the standalone CADe system was 93% at 6.4 FPs per patient on average, whereas the DCNN reduced the number of FPs to 2.0 per patient without reducing detection sensitivity. Most of the remaining FP detections were caused by untagged stool. In fecal-tagged CTC cases, the detection sensitivity was 94% at only 0.78 FPs per patient on average. These preliminary results indicate that DETALE can yield substantial improvement in the accuracy of automated polyp detection in CTC. C1 [Naeppi, Janne J.; Hironaka, Toru; Yoshida, Hiroyuki] Massachusetts Gen Hosp, 25 New Chardon St,Suite 4000, Boston, MA 02114 USA. [Naeppi, Janne J.; Hironaka, Toru; Yoshida, Hiroyuki] Harvard IJed Sch, 25 New Chardon St,Suite 4000, Boston, MA 02114 USA. [Regge, Daniele] Inst Canc Res & Treatment, Candiolo Str Prop 142, IT-10060 Turin, Italy. RP Nappi, JJ (reprint author), Massachusetts Gen Hosp, 25 New Chardon St,Suite 4000, Boston, MA 02114 USA.; Nappi, JJ (reprint author), Harvard IJed Sch, 25 New Chardon St,Suite 4000, Boston, MA 02114 USA. EM janne.nappi@mgh.harvard.edu; Yoshida.Hiro@mgh.harvard.edu NR 30 TC 0 Z9 0 U1 4 U2 4 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-5106-0020-1 J9 PROC SPIE PY 2015 VL 9785 AR UNSP 97852B DI 10.1117/12.2217260 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BG5QJ UT WOS:000389678800080 ER PT S AU Tachibana, R Kohlhase, N Naeppi, JJ Hironaka, T Ota, J Ishida, T Regge, D Yoshida, H AF Tachibana, Rie Kohlhase, Nadja Naeppi, Janne J. Hironaka, Toru Ota, Junko Ishida, Takayuki Regge, Daniele Yoshida, Hiroyuki BE Tourassi, GD Armato, SG TI Performance evaluation of multi-material electronic cleansing for ultra-low-dose dual-energy CT colonography SO MEDICAL IMAGING 2016: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Computer-Aided Diagnosis CY FEB 28-MAR 02, 2016 CL San Diego, CA SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, ImXPAD DE Colon; electronic cleansing; virtual cleansing; ultra-low-dose; dual-energy CT; virtual colonoscopy; random forest ID COMPUTED-TOMOGRAPHY AB Accurate electronic cleansing (EC) for CT colonography (CTC) enables the visualization of the entire colonic surface without residual materials. In this study, we evaluated the accuracy of a novel multi-material electronic cleansing (MUMA-EC) scheme for non-cathartic ultra-low-dose dual-energy CTC (DE-CTC). The MUMA-EC performs a water-iodine material decomposition of the DE-CTC images and calculates virtual monochromatic images at multiple energies, after which a random forest classifier is used to label the images into the regions of lumen air, soft tissue, fecal tagging, and two types of partial-volume boundaries based on image-based features. After the labeling, materials other than soft tissue are subtracted from the CTC images. For pilot evaluation, 384 volumes of interest (VOIs), which represented sources of subtraction artifacts observed in current EC schemes, were sampled from 32 ultra-low-dose DE-CTC scans. The voxels in the VOIs were labeled manually to serve as a reference standard. The metric for EC accuracy was the mean overlap ratio between the labels of the reference standard and the labels generated by the MUMA-EC, a dual-energy EC (DE-EC), and a single-energy EC (SE-EC) scheme. Statistically significant differences were observed between the performance of the MUMA/DE-EC and the SE-EC methods (p < 0.001). Visual assessment confirmed that the MUMA-EC generated less subtraction artifacts than did DE-EC and SE-EC. Our MUMA-EC scheme yielded superior performance over conventional SE-EC scheme in identifying and minimizing subtraction artifacts on non-cathartic ultra-low-dose DE-CTC images. C1 [Tachibana, Rie] Inst Natl Coll Technol, Dept Informat Sci & Technol, 1091-1 Komatsu Suo Oshima, Oshima 7422193, Japan. [Tachibana, Rie; Kohlhase, Nadja; Naeppi, Janne J.; Hironaka, Toru; Yoshida, Hiroyuki] Massachusetts Gen Hosp, Dept Radiol, Imaging Res 3D, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. [Tachibana, Rie; Kohlhase, Nadja; Naeppi, Janne J.; Hironaka, Toru; Yoshida, Hiroyuki] Harvard Med Sch, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. [Ota, Junko; Ishida, Takayuki] Osaka Univ, Dept Med Phys & Engn, 1-7 Yamadaoka, Suita, Osaka 5650871, Japan. [Regge, Daniele] Inst Canc Res & Treatment, Candiolo Str Prov 142, IT-10060 Turin, Italy. RP Tachibana, R (reprint author), Inst Natl Coll Technol, Dept Informat Sci & Technol, 1091-1 Komatsu Suo Oshima, Oshima 7422193, Japan.; Tachibana, R; Nappi, JJ; Yoshida, H (reprint author), Massachusetts Gen Hosp, Dept Radiol, Imaging Res 3D, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA.; Tachibana, R; Nappi, JJ; Yoshida, H (reprint author), Harvard Med Sch, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. EM tatibana@oshima-k.ac.jp; janne.nappi@mgh.harvard.edu; yoshida.hiro@mgh.harvard.edu NR 14 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-5106-0020-1 J9 PROC SPIE PY 2015 VL 9785 AR UNSP 978526 DI 10.1117/12.2217140 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BG5QJ UT WOS:000389678800076 ER PT S AU Tachibana, R Nappi, JJ Hironaka, T Kim, SH Yoshida, H AF Tachibana, Rie Nappi, Janne J. Hironaka, Tom Kim, Se Hyung Yoshida, Hiroyuki BE Tourassi, GD Armato, SG TI Deep learning for electronic cleansing in dual-energy CT colonography SO MEDICAL IMAGING 2016: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Computer-Aided Diagnosis CY FEB 28-MAR 02, 2016 CL San Diego, CA SP SPIE, Modus Med Devices Inc, Bruker, Poco Graphite, ImXPAD DE Deep learning; colon and other gastrointestinal tract; deep convolutional neural network; CT colonography; electronic cleansing; dual-energy CT AB The purpose of this study was to develop a novel deep-learning-based electronic cleansing (EC) method for dual-energy CT colonography (DE-CTC). In this method, an ensemble of deep convolutional neural networks (DCNNs) is used to classify each voxel of DE-CTC image volumes into one of five multi-material (MUMA) classes: luminal air, soft tissue, tagged fecal material, or a partial-volume boundary between air and tagging or that of soft tissue and tagging. Each DCNN acts as a voxel classifier. At each voxel, a region-of-interest (ROI) centered at the voxel is extracted. After mapping the pixels of the ROI to the input layer of a DCNN, a series of convolutional and max-pooling layers is used to extract features with increasing levels of abstraction. The output layer produces the probabilities at which the input voxel belongs to each of the five MUMA classes. To develop an ensemble of DCNNs, we trained multiple DCNNs based on multi-spectral image volumes derived from the DE-CTC images, including material decomposition images and virtual monochromatic images. The outputs of these DCNNs were then combined by means of a meta-classifier for precise classification of the voxels. Finally, the electronically cleansed CTC images were generated by removing regions that were classified as other than soft tissue, followed by colon surface reconstruction. Preliminary results based on 184,320 images sampled from 30 clinical CTC cases showed a higher accuracy in labeling these classes than that of our previous machine-learning methods, indicating that deep-learning-based multi-spectral EC can accurately remove residual fecal materials from CTC images without generating major EC artifacts. C1 [Tachibana, Rie] Inst Natl Coll Technol, Dept Informat Sci & Technol, 1091-1 Komatsu Suo Oshima, Oshima 7422193, Japan. [Tachibana, Rie; Nappi, Janne J.; Hironaka, Tom; Yoshida, Hiroyuki] Massachusetts Gen Hosp, Dept Radiol, Imaging Res 3D, Boston, MA 02114 USA. [Tachibana, Rie; Nappi, Janne J.; Hironaka, Tom; Yoshida, Hiroyuki] Harvard Med Sch, Boston, MA 02114 USA. [Kim, Se Hyung] Seoul Natl Univ Hosp, Seoul 110744, South Korea. RP Tachibana, R (reprint author), Inst Natl Coll Technol, Dept Informat Sci & Technol, 1091-1 Komatsu Suo Oshima, Oshima 7422193, Japan. EM tatibana@oshima-k.ac.jp; janne.nappi@mgh.harvard.edu; yoshida.hiro@mgh.harvard.edu NR 15 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-5106-0020-1 J9 PROC SPIE PY 2015 VL 9785 AR UNSP 97851M DI 10.1117/12.2216446 PG 7 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BG5QJ UT WOS:000389678800056 ER PT S AU Fenstermacher, SJ Pazyra-Murphy, MF Segal, RA AF Fenstermacher, Sara J. Pazyra-Murphy, Maria F. Segal, Rosalind A. BE Biffi, E TI Campenot Cultures and Microfluidics Provide Complementary Platforms for Spatial Study of Dorsal Root Ganglia Neurons SO MICROFLUIDIC AND COMPARTMENTALIZED PLATFORMS FOR NEUROBIOLOGICAL RESEARCH SE Neuromethods LA English DT Article; Book Chapter DE Neuroscience; Dorsal root ganglia (DRG) neurons; Campenot cultures; Microfluidics; Compartmented culture; Axonal RNA; Local protein synthesis; Neurotrophins ID RAT SYMPATHETIC NEURONS; NERVE GROWTH-FACTOR; NEWLY SYNTHESIZED PROTEINS; AXONAL MESSENGER-RNA; COMPARTMENTED CULTURES; LOCAL-CONTROL; NEURITE GROWTH; LIVING CELLS; TRKA; NEUROTROPHINS AB Dorsal root ganglia (DRG) neurons are a functionally diverse population of sensory neurons with specialized morphology to respond to external stimuli. These pseudo-unipolar neurons extend a single axon that bifurcates to innervate the periphery and spinal cord, allowing sensory information from the environment to be transferred rapidly to the central nervous system. During development, these DRG neurons rely on peripheral target-derived neurotrophins for survival. Due to their unique morphology, DRG neurons exhibit spatially complex signaling and regulated gene expression that are challenging to study in vivo or in conventional cultures. The development of compartmented culture systems has been invaluable to the study of neurotrophin signaling, mRNA transport and localization, and local protein synthesis in axons. Here we describe the setup and maintenance of rat DRG neurons in two different compartmented culture platforms: Campenot cultures and microfluidics chambers. These systems are highly complementary and so together can be used for biochemical analysis and for high resolution imaging of neuronal cell bodies and their extensive axons. C1 [Fenstermacher, Sara J.; Pazyra-Murphy, Maria F.; Segal, Rosalind A.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Fenstermacher, Sara J.; Pazyra-Murphy, Maria F.; Segal, Rosalind A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Fenstermacher, SJ (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. NR 35 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 0893-2336 BN 978-1-4939-2510-0; 978-1-4939-2509-4 J9 NEUROMETHODS JI Neuromethods PY 2015 VL 103 BP 105 EP 124 DI 10.1007/978-1-4939-2510-0_6 D2 10.1007/978-1-4939-2510-0 PG 20 WC Neurosciences SC Neurosciences & Neurology GA BE5AF UT WOS:000372458800008 ER PT J AU Arellano-Santoyo, H Stokasimov, E Su, X Pellman, DS AF Arellano-Santoyo, H. Stokasimov, E. Su, X. Pellman, D. S. TI Towards an understanding of the molecular mechanism of the unique biomechanical properties of the yeast kinesin-8 Kip3. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Arellano-Santoyo, H.; Stokasimov, E.; Pellman, D. S.] Harvard Med Sch, Cellular Biol, Boston, MA USA. [Arellano-Santoyo, H.; Stokasimov, E.; Su, X.; Pellman, D. S.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Arellano-Santoyo, H.; Stokasimov, E.; Pellman, D. S.] Dana Farber Canc Inst, Pediat Oncol, Boston, MA 02115 USA. [Su, X.] UCSF, Sch Med, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA M82 PG 2 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928400178 ER PT J AU Arellano-Santoyo, H Stokasimov, E Su, X Pellman, DS AF Arellano-Santoyo, H. Stokasimov, E. Su, X. Pellman, D. S. TI Towards an understanding of the molecular mechanism of the unique biomechanical properties of the yeast kinesin-8 Kip3 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Arellano-Santoyo, H.; Stokasimov, E.; Pellman, D. S.] Dana Farber Canc Inst, Pediat Oncol, Boston, MA 02115 USA. [Arellano-Santoyo, H.; Stokasimov, E.; Pellman, D. S.] Harvard Med Sch, Cellular Biol, Boston, MA USA. [Arellano-Santoyo, H.; Stokasimov, E.; Su, X.; Pellman, D. S.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Su, X.] UCSF, Sch Med, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P962 PG 2 WC Cell Biology SC Cell Biology GA V47BY UT WOS:000209928500151 ER PT J AU Baughman, E Tan, Y Ahmed, J Chatterjee, S Jackson, GR Ambegaokar, SS AF Baughman, E. Tan, Y. Ahmed, J. Chatterjee, S. Jackson, G. R. Ambegaokar, S. S. TI Negative feedback between miR-7 and its host gene hnRNP K/bancal by competitve binding to target mRNA, chico (insulin receptor substrate): implications for ERK, GSK-3beta and tau neurotoxicity SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Baughman, E.; Tan, Y.; Ahmed, J.; Ambegaokar, S. S.] Ohio Wesleyan Univ, Bot Microbiol, Delaware, OH 43015 USA. [Chatterjee, S.] Univ Texas Med Branch, Neurol, Galveston, TX 77555 USA. [Jackson, G. R.] DeBakey VA Med Ctr, Neurol, Houston, TX USA. [Jackson, G. R.] Baylor Coll Med, Neurol, Houston, TX 77030 USA. [Ambegaokar, S. S.] Ohio Wesleyan Univ, Neurosci, Delaware, OH 43015 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P1341 PG 1 WC Cell Biology SC Cell Biology GA V47BY UT WOS:000209928500527 ER PT J AU Gaudin, R Pasham, M Ma, M Kirchhausen, T AF Gaudin, R. Pasham, M. Ma, M. Kirchhausen, T. TI HIP1R AND THE COUPLING OF ACTIN TO ENDOCYTIC CLATHRIN-COATED PITS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Gaudin, R.; Kirchhausen, T.] Harvard Med Sch, Dept Cell Biol, Boston, MA USA. [Gaudin, R.; Pasham, M.; Ma, M.; Kirchhausen, T.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P1662 PG 1 WC Cell Biology SC Cell Biology GA V47BY UT WOS:000209928500856 ER PT J AU He, K Song, E Ma, M Gaudin, R Kirchhausen, T AF He, K. Song, E. Ma, M. Gaudin, R. Kirchhausen, T. TI Direct probing of dynamic phosphoinositide switches during clathrin-mediated endocytosis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [He, K.; Song, E.; Ma, M.; Gaudin, R.; Kirchhausen, T.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [He, K.; Song, E.; Ma, M.; Gaudin, R.; Kirchhausen, T.] Harvard Med Sch, Dept Cell Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA M36 PG 2 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928400083 ER PT J AU He, K Song, E Gaudin, R Ma, M Kirchhausen, T AF He, K. Song, E. Gaudin, R. Ma, M. Kirchhausen, T. TI The last five seconds in the life of a clathrin-coated vesicle SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [He, K.; Song, E.; Gaudin, R.; Ma, M.; Kirchhausen, T.] Harvard Med Sch, Dept Cell Biol, Boston, MA USA. [He, K.; Song, E.; Gaudin, R.; Ma, M.; Kirchhausen, T.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P1961 PG 2 WC Cell Biology SC Cell Biology GA V47BZ UT WOS:000209928600236 ER PT J AU Kardon, JR Yien, YY Huston, NC Branco, DS Hildick-Smith, GJ Moroco, JA Engen, JR Rhee, KY Paw, BH Baker, TA AF Kardon, J. R. Yien, Y. Y. Huston, N. C. Branco, D. S. Hildick-Smith, G. J. Moroco, J. A. Engen, J. R. Rhee, K. Y. Paw, B. H. Baker, T. A. TI Mitochondrial ClpX activates a key enzyme for heme biosynthesis and erythropoiesis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Kardon, J. R.; Baker, T. A.] MIT, Dept Biol, Cambridge, MA USA. [Yien, Y. Y.; Huston, N. C.; Branco, D. S.; Hildick-Smith, G. J.] Harvard Med Sch, Brigham & Womens Hosp, Div Hematol, Dept Med, Boston, MA USA. [Moroco, J. A.; Engen, J. R.] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA. [Rhee, K. Y.] Weill Cornell Med Coll, Div Infect Dis, Dept Med, New York, NY USA. [Rhee, K. Y.] Weill Cornell Med Coll, Dept Microbiol, New York, NY USA. [Paw, B. H.] Harvard Med Sch, Boston Childrens Hosp, Div Hematol Oncol, Dept Med, Boston, MA USA. [Paw, B. H.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Baker, T. A.] MIT, Howard Hughes Med Inst, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P2067 PG 2 WC Cell Biology SC Cell Biology GA V47BZ UT WOS:000209928600341 ER PT J AU Kvalvaag, AS Gaudin, R Villa, C Simm, R Sandvig, K Kirchhausen, T AF Kvalvaag, A. S. Gaudin, R. Villa, C. Simm, R. Sandvig, K. Kirchhausen, T. TI Shiga toxin 1 alters the dynamics of clathrin-mediated endocytosis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Kvalvaag, A. S.; Sandvig, K.] Norwegian Radium Hosp, Dept Mol Cell Biol, Oslo, Norway. [Kvalvaag, A. S.; Sandvig, K.] Univ Oslo, Dept Biosci, Oslo, Norway. [Kvalvaag, A. S.; Sandvig, K.] Univ Oslo, Ctr Canc Biomed, Oslo, Norway. [Gaudin, R.; Kirchhausen, T.] Harvard Med Sch, Dept Cell Biol, Boston, MA USA. [Gaudin, R.; Kirchhausen, T.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Villa, C.] European Inst Oncol, Program Mol Med, Milan, Italy. [Simm, R.] Norwegian Vet Inst, Oslo, Norway. [Kirchhausen, T.] Harvard Med Sch, Dept Pediat, Boston, MA USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P1975 PG 2 WC Cell Biology SC Cell Biology GA V47BZ UT WOS:000209928600249 ER PT J AU Liu, S Kwon, M Jackson, EK Spektor, A Pellman, DS AF Liu, S. Kwon, M. Jackson, E. K. Spektor, A. Pellman, D. S. TI Misregulation of nuclear envelope integrity in micronuclei leads to genome instability. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Liu, S.; Kwon, M.; Jackson, E. K.; Spektor, A.; Pellman, D. S.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Liu, S.; Kwon, M.; Jackson, E. K.; Pellman, D. S.] Harvard Med Sch, Dept Cell Biol, Boston, MA USA. [Jackson, E. K.; Pellman, D. S.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Spektor, A.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P336 PG 1 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928401363 ER PT J AU Loike, JD Jackson-Lewis, VR Behrman, B Fusman, L Graf, L Karaaslan, LE Levy, MY Miller, CS El Khoury, J Przedborski, S AF Loike, J. D. Jackson-Lewis, V. R. Behrman, B. Fusman, L. Graf, L. Karaaslan, L. E. Levy, M. Y. Miller, C. S. El Khoury, J. Przedborski, S. TI Role of Scavenger Receptors and beta-integrins in Microglial Interactions with Matrix-Bound Monomeric and Oligomeric Alpha-Synucleins. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Loike, J. D.; Behrman, B.; Fusman, L.; Graf, L.; Karaaslan, L. E.; Levy, M. Y.; Miller, C. S.] Columbia Univ, Physiol Cellular Biophys, New York, NY USA. [Jackson-Lewis, V. R.; Przedborski, S.] Columbia Univ, Pathol Cell Biol, New York, NY USA. [Behrman, B.; Miller, C. S.] Lander Coll Women, Biol, New York, NY USA. [Fusman, L.; Levy, M. Y.] Barnard Coll, Biol, New York, NY USA. [Graf, L.] Villanova Univ, Biol, Villanova, PA 19085 USA. [Karaaslan, L. E.] Columbia Coll, Biol, New York, NY USA. [El Khoury, J.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P2245 PG 1 WC Cell Biology SC Cell Biology GA V47BZ UT WOS:000209928600510 ER PT J AU Lopez, RAH Arellano-Santoyo, H Stokasimov, E Pellman, DS Leschziner, AE AF Lopez, R. A. Hernandez Arellano-Santoyo, H. Stokasimov, E. Pellman, D. S. Leschziner, A. E. TI Structural basis for processive motility and microtubule depolymerase activity by the yeast kinesin-8/Kip3 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Lopez, R. A. Hernandez; Leschziner, A. E.] Univ Calif San Diego, Dept Cellular & Mol Med, San Diego, CA 92103 USA. [Arellano-Santoyo, H.; Stokasimov, E.; Pellman, D. S.] Harvard Med Sch, Dept Cell Biol, Boston, MA USA. [Arellano-Santoyo, H.; Stokasimov, E.; Pellman, D. S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pellman, D. S.] Howard Hughes Med Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P929 PG 1 WC Cell Biology SC Cell Biology GA V47BY UT WOS:000209928500118 ER PT J AU Moore, TI Nordenfelt, P Mehta, S Lambert, T Swaminathan, V Mathew, JK Koga, N Baker, D Tani, T Mayor, S Waterman, CM Springer, TA AF Moore, T. I. Nordenfelt, P. Mehta, S. Lambert, T. Swaminathan, V. Mathew, J. K. Koga, N. Baker, D. Tani, T. Mayor, S. Waterman, C. M. Springer, T. A. TI Leukocyte integrin LFA-1 is aligned and oriented by actin flow during cell migration. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Moore, T. I.; Nordenfelt, P.; Springer, T. A.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Moore, T. I.; Nordenfelt, P.; Springer, T. A.] Harvard Med Sch, Biol Chem & Mol Pharmacol, Boston, MA USA. [Moore, T. I.; Nordenfelt, P.; Swaminathan, V.; Mathew, J. K.; Mayor, S.; Waterman, C. M.; Springer, T. A.] Marine Biol Lab, Whitman Ctr, Woods Hole, MA 02543 USA. [Nordenfelt, P.; Swaminathan, V.; Mathew, J. K.; Mayor, S.; Waterman, C. M.] Marine Biol Lab, Physiol Course, Woods Hole, MA 02543 USA. [Mehta, S.; Tani, T.] Marine Biol Lab, Eugene Bell Ctr, Woods Hole, MA 02543 USA. [Lambert, T.] Harvard Med Sch, Nikon Imaging Ctr, Boston, MA USA. [Swaminathan, V.; Waterman, C. M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. [Mathew, J. K.; Mayor, S.] Natl Ctr Biol Sci, TIFR, Bangalore, Karnataka, India. [Koga, N.; Baker, D.] Univ Washington, Biochem, Seattle, WA 98195 USA. [Baker, D.] Howard Hughes Med Inst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA E6 PG 2 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928400012 ER PT J AU Moore, TI Nordenfelt, P Mehta, S Lambert, T Swaminathan, V Mathew, JK Koga, N Baker, D Tani, T Mayor, S Waterman, CM Springer, TA AF Moore, T. I. Nordenfelt, P. Mehta, S. Lambert, T. Swaminathan, V. Mathew, J. K. Koga, N. Baker, D. Tani, T. Mayor, S. Waterman, C. M. Springer, T. A. TI Leukocyte integrin LFA-1 is aligned and oriented by actin flow during cell migration SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Moore, T. I.; Nordenfelt, P.; Springer, T. A.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Moore, T. I.; Nordenfelt, P.; Springer, T. A.] Harvard Med Sch, Biol Chem & Mol Pharmacol, Boston, MA USA. [Moore, T. I.; Nordenfelt, P.; Swaminathan, V.; Mathew, J. K.; Mayor, S.; Waterman, C. M.; Springer, T. A.] Marine Biol Lab, Whitman Ctr, Woods Hole, MA 02543 USA. [Nordenfelt, P.; Swaminathan, V.; Mathew, J. K.; Mayor, S.; Waterman, C. M.] Marine Biol Lab, Physiol Course, Woods Hole, MA 02543 USA. [Mehta, S.; Tani, T.] Marine Biol Lab, Eugene Bell Ctr, Woods Hole, MA 02543 USA. [Lambert, T.] Harvard Med Sch, Nikon Imaging Ctr, Boston, MA USA. [Swaminathan, V.; Waterman, C. M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. [Mathew, J. K.; Mayor, S.] Natl Ctr Biol Sci, TIFR, Bangalore, Karnataka, India. [Koga, N.; Baker, D.] Univ Washington, Biochem, Seattle, WA 98195 USA. [Koga, N.; Baker, D.] Howard Hughes Med Inst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P2153 PG 2 WC Cell Biology SC Cell Biology GA V47BZ UT WOS:000209928600427 ER PT J AU Saez, JC Cisterna, B Vargas, AA Cardozo, C AF Saez, J. C. Cisterna, B. Vargas, A. A. Cardozo, C. TI Acetylcholine prevents the expression of connexin hemichannels in denervated skeletal myofibers SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Saez, J. C.; Cisterna, B.; Vargas, A. A.] Pontificia Univ Catolica Chile, Dept Fisiol, Santiago, Chile. [Saez, J. C.; Cisterna, B.; Vargas, A. A.] Univ Valparaiso, Ctr Interdisciplinario Neurociencias Valparaiso, Milenio 4Inst, Valparaiso, Chile. [Cardozo, C.] James J Peters Vet Affairs Med Ctr, Excellence Med Consequences Spinal Cord 2Ctr, Bronx, NY USA. [Cardozo, C.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Cardozo, C.] Icahn Sch Med Mt Sinai, Dept Rehabil Med, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P2212 PG 2 WC Cell Biology SC Cell Biology GA V47BZ UT WOS:000209928600477 ER PT J AU Scarborough, EA Kudalkar, EM Umbreit, N Tien, J Asbury, CL Muller, E Davis, TN AF Scarborough, E. A. Kudalkar, E. M. Umbreit, N. Tien, J. Asbury, C. L. Muller, E. Davis, T. N. TI Regulation of Ndc80-based microtubule attachments by the central kinetochore Mis12/MIND complex suggests a folding-based molecular mechanism SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Scarborough, E. A.; Kudalkar, E. M.; Umbreit, N.; Tien, J.; Muller, E.; Davis, T. N.] Univ Washington, Biochem, Seattle, WA 98195 USA. [Kudalkar, E. M.] Partners Healthcare, Boston, MA USA. [Umbreit, N.] Dana Farber Canc Inst, Pediat, Boston, MA 02115 USA. [Tien, J.] BC Canc Agcy, Vancouver, BC, Canada. [Asbury, C. L.] Univ Washington, Physiol & Biophys, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P1839 PG 1 WC Cell Biology SC Cell Biology GA V47BZ UT WOS:000209928600114 ER PT J AU Spektor, A Cheng-Zhong, Z Umbreit, NT Cornils, H Francis, JM Jackson, EK Liu, S Meyerson, ML Pellman, DS AF Spektor, A. Cheng-Zhong, Z. Umbreit, N. T. Cornils, H. Francis, J. M. Jackson, E. K. Liu, S. Meyerson, M. L. Pellman, D. S. TI DNA damage and chromothripsis from chromosome segregation errors. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Spektor, A.] Dana Farber Canc Inst, Radiat Oncol, Boston, MA 02115 USA. [Spektor, A.; Cheng-Zhong, Z.; Umbreit, N. T.; Cornils, H.; Jackson, E. K.; Liu, S.; Pellman, D. S.] Dana Farber Canc Inst, Pediat Oncol, Boston, MA 02115 USA. [Spektor, A.; Cheng-Zhong, Z.; Umbreit, N. T.; Cornils, H.; Jackson, E. K.; Liu, S.; Pellman, D. S.] Harvard Med Sch, Cell Biol, Boston, MA USA. [Cheng-Zhong, Z.; Francis, J. M.; Meyerson, M. L.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Cheng-Zhong, Z.; Francis, J. M.; Meyerson, M. L.; Pellman, D. S.] Broad Inst Harvard & MIT, Boston, MA USA. [Jackson, E. K.; Pellman, D. S.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Meyerson, M. L.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Meyerson, M. L.] Harvard Med Sch, Pathol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA M27 PG 2 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928400074 ER PT J AU Umbreit, NT Spektor, A Cheng-Zhong, Z Leibowitz, M Francis, JM Meyerson, ML Pellman, DS AF Umbreit, N. T. Spektor, A. Cheng-Zhong, Z. Leibowitz, M. Francis, J. M. Meyerson, M. L. Pellman, D. S. TI A mechanism for chromosome bridge resolution based on nuclear envelope fragility and DNA damage SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Umbreit, N. T.; Spektor, A.; Cheng-Zhong, Z.; Leibowitz, M.; Pellman, D. S.] Dana Farber Canc Inst, Pediat Oncol, Boston, MA 02115 USA. [Umbreit, N. T.; Spektor, A.; Cheng-Zhong, Z.; Leibowitz, M.; Pellman, D. S.] Harvard Med Sch, Cell Biol, Boston, MA USA. [Spektor, A.] Dana Farber Canc Inst, Radiat Oncol, Boston, MA 02115 USA. [Cheng-Zhong, Z.; Francis, J. M.; Meyerson, M. L.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Cheng-Zhong, Z.; Francis, J. M.; Meyerson, M. L.; Pellman, D. S.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Meyerson, M. L.] Harvard Med Sch, Dept Pathol, Boston, MA USA. [Meyerson, M. L.] Dana Farber Canc Inst, Ctr Canc Genome, Boston, MA 02115 USA. [Pellman, D. S.] Howard Hughes Med Inst, Chevy Chase, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P1788 PG 2 WC Cell Biology SC Cell Biology GA V47BZ UT WOS:000209928600063 ER PT J AU VanDenHeuvel, KJ Jambhekar, A Shivas, JM Qin, L Olukoga, O Blower, MD Skop, AR AF VanDenHeuvel, K. J. Jambhekar, A. Shivas, J. M. Qin, L. Olukoga, O. Blower, M. D. Skop, A. R. TI Characterization of the mammalian midbody transcriptome reveals important factors necessary for cell fate determination SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [VanDenHeuvel, K. J.; Qin, L.; Olukoga, O.; Skop, A. R.] Univ Wisconsin Madison, Lab Genet & Med Genet, Madison, WI USA. [Jambhekar, A.; Blower, M. D.] Harvard Univ, Massachusetts Gen Hosp, Dept Mol Biol & Genet, Boston, MA USA. [Shivas, J. M.] Leica Microsyst, Allendale, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P1555 PG 2 WC Cell Biology SC Cell Biology GA V47BY UT WOS:000209928500740 ER PT J AU Wong, VC Chavali, AK Lee, RE Mothes, W Gaudet, S Miller-Jensen, K AF Wong, V. C. Chavali, A. K. Lee, R. E. Mothes, W. Gaudet, S. Miller-Jensen, K. TI Chromatin modifies the transmission of TNF-induced NF-kappa B signals in single cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Wong, V. C.; Miller-Jensen, K.] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT USA. [Chavali, A. K.; Miller-Jensen, K.] Yale Univ, Dept Biomed Engn, New Haven, CT USA. [Lee, R. E.] Univ Pittsburgh, Dept Computat & Syst Biol, Sch Med, Pittsburgh, PA USA. [Lee, R. E.; Gaudet, S.] Harvard Med Sch, Dept Genet, Boston, MA USA. [Lee, R. E.; Gaudet, S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Lee, R. E.; Gaudet, S.] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Mothes, W.] Yale Univ, Dept Microbial Pathogenesis, Sch Med, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P293 PG 1 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928401320 ER PT J AU Wong, VC Chavali, AK Lee, RE Mothes, W Gaudet, S Miller-Jensen, K AF Wong, V. C. Chavali, A. K. Lee, R. E. Mothes, W. Gaudet, S. Miller-Jensen, K. TI Chromatin modifies the transmission of TNF-induced NF-kappa B signals in single cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Wong, V. C.; Miller-Jensen, K.] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT USA. [Chavali, A. K.; Miller-Jensen, K.] Yale Univ, Dept Biomed Engn, New Haven, CT USA. [Lee, R. E.] Univ Pittsburgh, Sch Med, Dept Computat & Syst Biol, Pittsburgh, PA USA. [Lee, R. E.; Gaudet, S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Lee, R. E.; Gaudet, S.] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Lee, R. E.; Gaudet, S.] Harvard Med Sch, Dept Genet, Boston, MA USA. [Mothes, W.] Yale Univ, Sch Med, Dept Microbial Pathogenesis, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA M190 PG 1 WC Cell Biology SC Cell Biology GA V47BX UT WOS:000209928400345 ER PT J AU Zalli, D Neff, L Takeyama, K Nagano, K Gori, F Witke, W Baron, RE AF Zalli, D. Neff, L. Takeyama, K. Nagano, K. Gori, F. Witke, W. Baron, R. E. TI The actin-binding protein Cofilin and its interaction with cortactin are required for podosome patterning in osteoclasts and bone resorption in vivo and in vitro SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Zalli, D.; Neff, L.; Takeyama, K.; Nagano, K.; Gori, F.; Baron, R. E.] Harvard Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA USA. [Witke, W.] Univ Bonn, Endocrine Unit, Inst Genet, Bonn, Germany. [Baron, R. E.] Harvard Med Sch, Dept Med, Boston, MA USA. [Baron, R. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2015 VL 26 MA P1731 PG 2 WC Cell Biology SC Cell Biology GA V47BZ UT WOS:000209928600006 ER PT J AU Holmes, AJ Hollinshead, MO O'Keefe, TM Petrov, VI Fariello, GR Wald, LL Fischl, B Rosen, BR Mair, RW Roffman, JL Smoller, JW Buckner, RL AF Holmes, Avram J. Hollinshead, Marisa O. O'Keefe, Timothy M. Petrov, Victor I. Fariello, Gabriele R. Wald, Lawrence L. Fischl, Bruce Rosen, Bruce R. Mair, Ross W. Roffman, Joshua L. Smoller, Jordan W. Buckner, Randy L. TI Brain Genomics Superstruct Project initial data release with structural, functional, and behavioral measures SO SCIENTIFIC DATA LA English DT Article AB The goal of the Brain Genomics Superstruct Project (GSP) is to enable large-scale exploration of the links between brain function, behavior, and ultimately genetic variation. To provide the broader scientific community data to probe these associations, a repository of structural and functional magnetic resonance imaging (MRI) scans linked to genetic information was constructed from a sample of healthy individuals. The initial release, detailed in the present manuscript, encompasses quality screened cross-sectional data from 1,570 participants ages 18 to 35 years who were scanned with MRI and completed demographic and health questionnaires. Personality and cognitive measures were obtained on a subset of participants. Each dataset contains a T1-weighted structural MRI scan and either one (n = 1,570) or two (n = 1,139) resting state functional MRI scans. Test-retest reliability datasets are included from 69 participants scanned within six months of their initial visit. For the majority of participants self-report behavioral and cognitive measures are included (n = 926 and n = 892 respectively). Analyses of data quality, structure, function, personality, and cognition are presented to demonstrate the dataset's utility. C1 [Holmes, Avram J.; Hollinshead, Marisa O.; O'Keefe, Timothy M.; Petrov, Victor I.; Fariello, Gabriele R.; Mair, Ross W.; Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Holmes, Avram J.; Hollinshead, Marisa O.; Buckner, Randy L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Holmes, Avram J.; Fariello, Gabriele R.; Roffman, Joshua L.; Smoller, Jordan W.; Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Holmes, Avram J.; Fariello, Gabriele R.; Roffman, Joshua L.; Smoller, Jordan W.; Buckner, Randy L.] Harvard Med Sch, Boston, MA 02114 USA. [Holmes, Avram J.; Hollinshead, Marisa O.; Wald, Lawrence L.; Fischl, Bruce; Rosen, Bruce R.; Mair, Ross W.; Roffman, Joshua L.; Buckner, Randy L.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Res, Charlestown, MA 02129 USA. [Holmes, Avram J.; Hollinshead, Marisa O.; Wald, Lawrence L.; Fischl, Bruce; Rosen, Bruce R.; Mair, Ross W.; Roffman, Joshua L.; Buckner, Randy L.] Harvard Med Sch, Charlestown, MA 02129 USA. RP Roffman, JL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM jroffman@partners.org; jsmoller@hms.harvard.edu; randy_buckner@harvard.edu FU Shared Instrumentation [1S10RR023043, 1S10RR023401]; Simons Foundation; Howard Hughes Medical Institute; NIMH [R01-MH079799, K24MH094614, K01MH099232]; Massachusetts General Hospital-University of Southern California Human Connectome Project [U54MH091665] FX AJH is presently affiliated with the Yale University Department of Psychology. GRF is presently affiliated with the Harvard University School of Engineering and Applied Sciences. We thank Jamie Plenge, Elizabeth Hemphill, Katherine Powers, Renee Poulin, Glenn Hoffman, Leah Bakst, David Brohawn, Sara Rubenstein, Emily Shire, Susanna Crowell, Michelle Zad, Michelle Drews, and Elizabeth Beam for their dedication to the project, including intensive data collection and extensive quality control. We thank the Harvard Center for Brain Science, Harvard FAS Research Computing, and the Athinoula A. Martinos Center for Biomedical Imaging for imaging and computational support, and the Center for Human Genetic Research and the Stanley Center for Psychiatric Research for genetics support. Thomas Benner and Gregory Sorensen assisted in developing the initial fast imaging protocol. Hesheng Liu, Danhong Wang, Jessica Tandi, and BT Thomas Yeo provided feedback and support on the paper figures. Abid Qureshi and Mark Eldaief assisted with data quality control. Xi-Nian Zuo provided feedback on aspects of the fALFF analyses. Lisa-Feldman Barrett, Joshua Greene, Trey Hedden, Daphne Holt, Jian Kong, Moh Milad, Jason Mitchell, Diego Pizzagalli, and Daniel Schacter generously contributed data to the present release. The Institute for Quantitative Social Science at Harvard University is supporting data distribution through the Dataverse Network Project. Additional data distribution is supported through the Laboratory of Neuroimaging (LONI) at the Keck School of Medicine of the University of Southern California in conjunction with the MGH-USC Human Connectome Project. This work was made possible by the resources provided through Shared Instrumentation Grants 1S10RR023043 and 1S10RR023401 and was supported by funding from the Simons Foundation (RLB), the Howard Hughes Medical Institute (RLB), NIMH grants R01-MH079799 (JWS), K24MH094614 (JWS), K01MH099232 (AJH), and the Massachusetts General Hospital-University of Southern California Human Connectome Project (U54MH091665). NR 79 TC 7 Z9 7 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2052-4463 J9 SCI DATA JI Sci. Data PY 2015 VL 2 AR 150031 DI 10.1038/sdata.2015.31 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V45VM UT WOS:000209844100028 PM 26175908 ER PT J AU Kulaga-Yoskovitz, J Bernhardt, BC Hong, SJ Mansi, T Liang, KE van der Kouwe, AJW Smallwood, J Bernasconi, A Bernasconi, N AF Kulaga-Yoskovitz, Jessie Bernhardt, Boris C. Hong, Seok-Jun Mansi, Tommaso Liang, Kevin E. van der Kouwe, Andre J. W. Smallwood, Jonathan Bernasconi, Andrea Bernasconi, Neda TI Multi-contrast submillimetric 3Tesla hippocampal subfield segmentation protocol and dataset SO SCIENTIFIC DATA LA English DT Article AB The hippocampus is composed of distinct anatomical subregions that participate in multiple cognitive processes and are differentially affected in prevalent neurological and psychiatric conditions. Advances in high-field MRI allow for the non-invasive identification of hippocampal substructure. These approaches, however, demand time-consuming manual segmentation that relies heavily on anatomical expertise. Here, we share manual labels and associated high-resolution MRI data (MNI-HISUB25; submillimetric T1- and T-2-weighted images, detailed sequence information, and stereotaxic probabilistic anatomical maps) based on 25 healthy subjects. Data were acquired on a widely available 3 Tesla MRI system using a 32 phased-array head coil. The protocol divided the hippocampal formation into three subregions: subicular complex, merged Cornu Ammonis 1, 2 and 3 (CA(1-3)) subfields, and CA(4)-dentate gyrus (CA4-DG). Segmentation was guided by consistent intensity and morphology characteristics of the densely myelinated molecular layer together with few geometry-based boundaries flexible to overall mesiotemporal anatomy, and achieved excellent intra-/inter-rater reliability (Dice index >= 90/87%). The dataset can inform neuroimaging assessments of the mesiotemporal lobe and help to develop segmentation algorithms relevant for basic and clinical neurosciences. C1 [Kulaga-Yoskovitz, Jessie; Bernhardt, Boris C.; Hong, Seok-Jun; Liang, Kevin E.; Bernasconi, Andrea; Bernasconi, Neda] McGill Univ, Dept Neurol & Neurosurg, Neuroimaging Epilepsy Lab, Montreal, PQ H3A 2B4, Canada. [Kulaga-Yoskovitz, Jessie; Bernhardt, Boris C.; Hong, Seok-Jun; Liang, Kevin E.; Bernasconi, Andrea; Bernasconi, Neda] McGill Univ, McConnell Brain Imaging Ctr, Montreal, PQ H3A 2B4, Canada. [Bernhardt, Boris C.] Max Planck Inst Human Cognit & Brain Sci, Dept Social Neurosci, D-04303 Leipzig, Germany. [Mansi, Tommaso] Siemens Med Solut USA Inc, Med Imaging Technol, Healthcare Technol Ctr, Princeton, NJ 08540 USA. [van der Kouwe, Andre J. W.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Smallwood, Jonathan] York Univ, Dept Psychol, York YO10 5DD, N Yorkshire, England. RP Bernasconi, N (reprint author), McGill Univ, Dept Neurol & Neurosurg, Neuroimaging Epilepsy Lab, Montreal, PQ H3A 2B4, Canada.; Bernasconi, N (reprint author), McGill Univ, McConnell Brain Imaging Ctr, Montreal, PQ H3A 2B4, Canada. EM neda@bic.mni.mcgill.ca FU Canadian Institutes of Health Research [CIHR MOP-57840, CIHR MOP-123520] FX This work was supported by the Canadian Institutes of Health Research (CIHR MOP-57840 and CIHR MOP-123520). NR 34 TC 0 Z9 0 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 2015 VL 2 AR 150059 DI 10.1038/sdata.2015.59 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V45VM UT WOS:000209844100059 ER PT J AU Bressler, SB Edwards, AR Andreoli, CM Edwards, PA Glassman, AR Jaffe, GJ Melia, M Sun, JK AF Bressler, Susan B. Edwards, Allison R. Andreoli, Christopher M. Edwards, Paul Andrew Glassman, Adam R. Jaffe, Glenn J. Melia, Michele Sun, Jennifer K. CA Diabetic Retinopathy Clinical Res TI Reproducibility of Optovue RTVue Optical Coherence Tomography Retinal Thickness Measurements and Conversion to Equivalent Zeiss Stratus Metrics in Diabetic Macular Edema SO TRANSLATIONAL VISION SCIENCE & TECHNOLOGY LA English DT Article DE diabetic macular edema; optical coherence tomography; retinal thickness measurements ID EYES; OCT AB Purpose: To evaluate the reproducibility of central subfield thickness (CST) and volume measurements from optical coherence tomography (OCT) images obtained with Zeiss Stratus and Optovue RTVue, and formulate equations to convert these measurements from RTVue to ` equivalent' Stratus values. Methods: Cross-sectional observational study from 309 eyes of 167 participants with diabetes and at least one eye with central-involved diabetic macular edema (DME; Stratus CST >= 250 mu m) that underwent two replicate Stratus scans followed by two replicate RTVue scans centered on the fovea. Results: The Bland-Altman coefficient of repeatability for relative change in CST (the degree of change that could be expected from measurement variability) was not significantly different on Stratus and RTVue scans (10% and 16%, respectively). The replicate Stratus CST was within 10% of the initial Stratus measurement 93% of the time; the CST conversion equation predicted a Stratus value calculated from the observed RTVue value within 10% of the observed Stratus thickness 91% of the time. Bland-Altman limit of agreement for relative change in CST between measurements observed on different machines was 23%, comparing predicted versus actual Stratus measurement. Conclusions: RTVue thickness reproducibility appears similar to Stratus. Conversion equations to transform RTVue measurements to Stratus-equivalent values within 10% of the observed Stratus RT are feasible. CST changes greater than 10% when using the same machine or 20% when switching from Stratus to RTVue, after conversion to Stratus equivalents, are likely due to a true change beyond measurement error. C1 [Bressler, Susan B.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. [Edwards, Allison R.; Glassman, Adam R.; Melia, Michele] Jaeb Ctr Hlth Res, Tampa, FL USA. [Andreoli, Christopher M.] Harvard Med Sch, Dept Ophthalmol, Harvard Vanguard Med Associates, Boston, MA USA. [Edwards, Paul Andrew] Henry Ford Hlth Syst, Dept Ophthalmol, Detroit, MI USA. [Edwards, Paul Andrew] Henry Ford Hlth Syst, Eye Care Serv, Detroit, MI USA. [Jaffe, Glenn J.] Duke Univ, Dept Ophthalmol, Durham, NC USA. [Sun, Jennifer K.] Harvard Univ, Dept Ophthalmol, Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02115 USA. RP Edwards, AR (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Suite 350, Tampa, FL 33647 USA. EM drcrstat1@jaeb.org FU National Eye Institute, National Institutes of Health, US Department of Health and Human Services [EY14231, EY018817]; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, US Department of Health and Human Services [EY14231, EY018817] FX Supported by grants through a cooperative agreement from the National Eye Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, US Department of Health and Human Services (Grants EY14231 and EY018817). NR 13 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 2164-2591 J9 TRANSL VIS SCI TECHN JI Transl. Vis. Sci. Technol. PD JAN PY 2015 VL 4 IS 1 AR 5 DI 10.1167/tvst.4.1.5 PG 11 WC Ophthalmology SC Ophthalmology GA ED0WE UT WOS:000388562500005 PM 25635237 ER PT J AU Carruthers, MN Khosroshahi, A Augustin, T Deshpande, V Stone, JH AF Carruthers, Mollie N. Khosroshahi, Arezou Augustin, Tamara Deshpande, Vikram Stone, John H. TI The diagnostic utility of serum IgG4 concentrations in IgG4-related disease SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID AUTOIMMUNE PANCREATITIS AB Objectives We evaluated the sensitivity, specificity and positive and negative predictive values of elevated serum IgG4 concentrations for the diagnosis of IgG4-RD. Methods Between 2001 and 2011, 190 unique patients had elevated serum IgG4 measurements. We reviewed electronic medical records to determine the indication for IgG4 measurement and underlying clinical diagnosis. Additionally, we reviewed the records of 190 other randomly selected patients from a pool of 3360 with normal results, to evaluate test characteristics of the IgG4 measurement. Results Among 380 patients analysed, 72 had either probable or definite IgG4-RD. Sixty-five of the 72 IgG4-RD patients had elevated serum IgG4 concentrations (mean: 405 mg/dL; range 140-2000 mg/dL), for a sensitivity of 90%. Among the 308 subjects without IgG4-RD, 125 had elevated IgG4 (mean: 234 mg/dL; range 135-1180 mg/dL) and 183 had normal IgG4 concentrations, for a specificity of 60%. The negative predictive value of a serum IgG4 assay was 96%, but the positive predictive value only 34%. Analysis of the serum IgG4/total IgG ratio did not improve these test characteristics. Doubling the cutoff for IgG4 improved specificity (91%) but decreased sensitivity to 35%. Discussion Multiple non-IgG4-RD conditions are associated with elevated serum IgG4, leading to poor specificity and low positive predictive value for this test. A substantial subset of patients with biopsy-proven IgG4-RD do not have elevated serum IgG4. Neither doubling the cutoff for serum IgG4 nor examining the serum IgG4/IgG ratio improves the overall test characteristics for the diagnosis of IgG4-RD. C1 [Carruthers, Mollie N.; Stone, John H.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Dept Med, Rheumatol Unit, Boston, MA 02114 USA. [Carruthers, Mollie N.; Stone, John H.] Harvard Univ, Sch Med, Boston, MA USA. [Khosroshahi, Arezou] Emory Univ, Sch Med, Dept Med, Div Rheumatol, Atlanta, GA USA. [Augustin, Tamara] North Shore Hosp, Dept Med, Salem, MA USA. [Deshpande, Vikram] MGH, Dept Pathol, Boston, MA USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, 55 Fruit St, Boston, MA 02114 USA. EM jhstone@partners.org NR 14 TC 73 Z9 79 U1 2 U2 10 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JAN PY 2015 VL 74 IS 1 BP 14 EP 18 DI 10.1136/annrheumdis-2013-204907 PG 5 WC Rheumatology SC Rheumatology GA AU9XT UT WOS:000345945700014 PM 24651618 ER PT J AU Wallace, ZS Mattoo, H Carruthers, M Mahajan, VS Della Torre, E Lee, H Kulikova, M Deshpande, V Pillai, S Stone, JH AF Wallace, Zachary S. Mattoo, Hamid Carruthers, Mollie Mahajan, Vinay S. Della Torre, Emanuel Lee, Hang Kulikova, Maria Deshpande, Vikram Pillai, Shiv Stone, John H. TI Plasmablasts as a biomarker for IgG4-related disease, independent of serum IgG4 concentrations SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; B-LYMPHOCYTE HOMEOSTASIS; ULCERATIVE-COLITIS; PERIPHERAL-BLOOD; CELLS; EXPRESSION; RITUXIMAB; FIBROSIS AB Objectives We examined the utility of circulating total and IgG4+ plasmablasts as biomarkers of diagnosis and disease activity in IgG4-related disease (IgG4-RD). Materials methods We evaluated patients with active, untreated, biopsy-proven IgG4-RD affecting various organs. Flow cytometry was used to measure total plasmablast and IgG4+ plasmablast counts by gating peripheral blood for CD19lowCD38+CD20-CD27 + cells and CD19lowCD38+CD20-CD27+IgG4+ cells. Serum IgG4 concentrations were measured by nephelometry. We compared 37 IgG4-RD patients to 35 controls, including healthy individuals (n=14) and patients with other inflammatory diseases before treatment (n=21). Results The IgG4-RD patients' mean age was 59, and 68% were male. Fourteen patients (38%) had three or more organs involved. The IgG4-RD patients had substantially elevated total plasmablast counts (median 4698/mL, range 610-79524/mL) compared to both untreated disease controls (median 592/mL, range 19-4294/mL; p < 0.001) and healthy controls (median 94/mL, range 1-653/mL; p < 0.001). Thirteen IgG4-RD patients (36%) had normal serum IgG4 concentrations (mean 60 mg/dL, range 5-123 mg/dL, normal < 135 mg/dL). However, the median plasmablast count was not significantly lower in that subset with normal serum IgG4 concentrations (3784/mL) compared to those with elevated serum IgG4 (5155/mL) (p = 0.242). Among the 12 rituximab (RTX)-treated patients, the median plasmablast level during disease flare was 6356/mL (range 112341589/mL), declining to 1419/mL (range 386/mL-4150/mL) during remission (p < 0.01). Conclusions Circulating plasmablasts are elevated in active IgG4-RD, even in patients with normal serum IgG4 concentrations. Plasmablast counts are a potentially useful biomarker for diagnosis, assessing response to treatment, and determining the appropriate time for re-treatment. C1 [Wallace, Zachary S.; Carruthers, Mollie; Stone, John H.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Mattoo, Hamid; Mahajan, Vinay S.; Della Torre, Emanuel; Kulikova, Maria; Pillai, Shiv] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Lee, Hang] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Clin Yawkey 2, 55 Fruit St, Boston, MA 02114 USA. EM jhstone@partners.org OI Della Torre, Emanuel/0000-0002-9192-4270 FU National Institutes of Health [AI 064930, AI 076505]; Harvard Institute of Translational Immunology - Helmsley Foundation FX This study was funded by grants AI 064930 and AI 076505 from the National Institutes of Health and a pilot grant from the Harvard Institute of Translational Immunology supported by the Helmsley Foundation. NR 37 TC 80 Z9 82 U1 3 U2 10 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JAN PY 2015 VL 74 IS 1 BP 190 EP 195 DI 10.1136/annrheumdis-2014-205233 PG 6 WC Rheumatology SC Rheumatology GA AU9XT UT WOS:000345945700039 PM 24817416 ER PT B AU Yang, EY Nambi, V AF Yang, Eric Y. Nambi, Vijay BE Wong, ND Amsterdam, EA Blumenthal, RS TI Role of Carotid Intima-Media Thickness Assessment in Preventative Cardiology SO ASPC MANUAL OF PREVENTIVE CARDIOLOGY LA English DT Article; Book Chapter ID CORONARY-HEART-DISEASE; SERVICES TASK-FORCE; ATHEROSCLEROSIS RISK; CARDIOVASCULAR-DISEASE; WALL THICKNESS; 3-DIMENSIONAL ULTRASOUND; VASCULAR MEDICINE; AMERICAN SOCIETY; ARTERY-DISEASE; PLAQUE C1 [Yang, Eric Y.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Nambi, Vijay] Baylor Coll Med, Dept Med, Michael E DeBakey Vet Affairs Med Ctr,Sect Cardio, Ctr Cardiovasc Prevent,Methodist DeBakey Heart &, Houston, TX 77030 USA. RP Yang, EY (reprint author), Baylor Coll Med, Dept Med, Houston, TX 77030 USA. NR 46 TC 0 Z9 0 U1 0 U2 1 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-86-4 PY 2015 BP 118 EP 129 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BB5RG UT WOS:000344034500014 ER PT J AU Jakobiec, FA Roh, M Stagner, AM Yoon, MK AF Jakobiec, Frederick A. Roh, Miin Stagner, Anna M. Yoon, Michael K. TI Caruncular Dacryops SO CORNEA LA English DT Article DE conjunctival cyst; dacryops; caruncle; cytokeratin; immunohistochemistry ID LESIONS; GLAND AB Purpose: To report a case of caruncular dacryops in a 58-year-old man that was excised in its entirety and to offer an immunohistopathologic analysis. Methods: Sections stained with hematoxylin and eosin, periodic acid-Schiff, and Grocott methenamine silver (the latter 2 for identification of mucus) were evaluated, and immunohistochemical investigations were performed using cytokeratin (CK) 7, CK14, CK17, and smooth muscle actin. Results: Histopathologic examination revealed a cystic dilation of the lacrimal gland ducts containing secretory globules. The ducts were composed of double-layered cuboidal epithelium with rare scattered goblet cells and interspersed prominent lobules of lacrimal gland tissue, diagnostic of dacryops. Immunohistochemistry of cystic ducts demonstrated a CK profile identical to that of the conjunctiva including the absence of a myoepithelium. Conclusions: This is the first case of an intact caruncular lacrimal ductal cyst (dacryops). A previous report documented a spontaneously collapsed cyst with extrusion of secretory globoid bodies into extracellular space that elicited a foreign body giant cell response. C1 [Jakobiec, Frederick A.; Roh, Miin; Stagner, Anna M.; Yoon, Michael K.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Jakobiec, Frederick A.; Stagner, Anna M.] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Yoon, Michael K.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Suite 328,243 Charles St, Boston, MA 02114 USA. EM fred_jakobiec@meei.harvard.edu NR 10 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 EI 1536-4798 J9 CORNEA JI Cornea PD JAN PY 2015 VL 34 IS 1 BP 107 EP 109 PG 3 WC Ophthalmology SC Ophthalmology GA AU9OR UT WOS:000345924700027 PM 25357082 ER PT J AU Wallace, ZS Stone, JH AF Wallace, Zachary S. Stone, John H. TI An update on IgG4-related disease SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE fibrosis; IgG4; IgG4-related disease; plasmablast; pseudotumour ID PRIMARY SCLEROSING CHOLANGITIS; SERUM IGG4 CONCENTRATIONS; LABIAL SALIVARY-GLANDS; AUTOIMMUNE PANCREATITIS; IMMUNOGLOBULIN G4; SYSTEMIC-DISEASE; DIAGNOSTIC UTILITY; MIKULICZS-DISEASE; FREQUENCY; MANIFESTATIONS AB Purpose of reviewIgG4-related disease (IgG4-RD) is a recently described fibroinflammatory condition that can affect nearly any organ. Our knowledge of this condition - its manifestations, diagnosis, pathogenesis and treatment - is expanding rapidly.Recent findingsThis review highlights the most recent developments in the field. Particular highlights include new manifestations of the disease, studies on the test characteristics of serum IgG4 concentrations in the diagnosis of IgG4-RD, descriptions of the lack of specificity of IgG4+ plasma cells in histopathological samples and preliminary research on unique B and T lymphocyte populations in the disease.SummaryFuture studies might focus on identifying biomarkers to assist with noninvasive diagnosis of IgG4-RD and conducting trials of novel treatments that might supplant glucocorticoids as the treatment of choice. C1 [Wallace, Zachary S.; Stone, John H.] Massachusetts Gen Hosp, Boston, MA USA. [Stone, John H.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, Yawkey 2,55 Fruit St, Boston, MA 02114 USA. EM jhstone@mgh.harvard.edu NR 68 TC 10 Z9 11 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 EI 1531-6963 J9 CURR OPIN RHEUMATOL JI Curr. Opin. Rheumatol. PD JAN PY 2015 VL 27 IS 1 BP 83 EP 90 DI 10.1097/BOR.0000000000000133 PG 8 WC Rheumatology SC Rheumatology GA AU7DE UT WOS:000345760000012 PM 25415530 ER PT J AU Tabatabaei, S Zangi, M AF Tabatabaei, Shahin Zangi, Mahdi TI Outpatient surgery for lower urinary tract symptoms/benign prostatic hyperplasia: truth or myth? SO CURRENT OPINION IN UROLOGY LA English DT Review DE ambulatory surgical procedures; benign prostatic hyperplasia; bipolar plasma vaporization; laser therapy; microwaves ID PROSTATECTOMY; VAPORIZATION; TERM; MEN AB Purpose of review Worldwide, lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) is a common medical problem for aging men. Of patients who seek help with their symptoms, almost one-third do not respond to the medical therapy. These patients need a procedure that is safe, efficient, and durable, and at the same time carries minimal risk of side-effects. Many new technologies are introduced to our medical practice with the promise of being the ideal office-based procedure. In this review, we intend to review and discuss the role of three surgical procedures in an office setting. These include thermotherapy, 532-nm laser photo-selective vaporization of prostate, and bipolar plasma vaporization of prostate. Recent findings There are a few recent thermotherapy studies regarding the outcome of thermotherapy in LUTS/BPH patients. Data regarding the use of 532-ng laser photo-selective vaporization of prostate are scant but promising. The use of bipolar plasma vaporization is not well studied in an office setting. Summary In a select group of patients, thermotherapy and laser prostate surgery could be safely used to treat LUTS/BPH patients. Bipolar plasma vaporization is a promising technology, but its use in an office setting has not been completely evaluated yet. C1 [Tabatabaei, Shahin; Zangi, Mahdi] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Tabatabaei, S (reprint author), Massachusetts Gen Hosp, Dept Urol, GRB 1102,55 Fruit St, Boston, MA 02114 USA. EM stabatabaei@partners.org NR 15 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0963-0643 EI 1473-6586 J9 CURR OPIN UROL JI Curr. Opin. Urol. PD JAN PY 2015 VL 25 IS 1 BP 27 EP 31 DI 10.1097/MOU.0000000000000127 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA AU5EE UT WOS:000345629200005 PM 25393275 ER PT J AU Hsiao, JJ Lu, PH Grill, JD Teng, E AF Hsiao, Julia J. Lu, Po H. Grill, Joshua D. Teng, Edmond TI Longitudinal Declines in Instrumental Activities of Daily Living in Stable and Progressive Mild Cognitive Impairment SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Mild cognitive impairment; Dementia; Diagnosis; Activities of daily living; Functional abilities; Assessment measures ID ALZHEIMERS ASSOCIATION WORKGROUPS; VASCULAR RISK-FACTORS; DIAGNOSTIC GUIDELINES; FUNCTIONAL-ACTIVITIES; NATIONAL INSTITUTE; EVERYDAY FUNCTION; SYDNEY MEMORY; OLDER-ADULTS; DISEASE; DEMENTIA AB Background: Previous cross-sectional studies suggest that assessments of instrumental activities of daily living (IADLs) may be useful for operationalizing the differences in functional deficits seen in mild cognitive impairment (MCI) and dementia. However, their utility for longitudinal changes in IADLs in the transition between MCI and dementia remains unclear. Methods: We analyzed longitudinal IADL data with the Functional Activities Questionnaire (FAQ) in stable (MCI-S; n = 1,318) or progressive (MCI-P; n = 1,108) MCI patients. Results: Larger increases in FAQ scores were seen in the MCI-P group across a 14.5-month interval, but overlapping distributions in the two groups yielded poorer discriminatory power than prior cross-sectional reports. Conclusion: Our findings emphasize the difficulties in operationalizing the criterion of 'essentially intact' IADLs in MCI, which may complicate the interpretation of disease progression in MCI treatment trials. (C) 2014 S. Karger AG, Basel C1 [Hsiao, Julia J.; Lu, Po H.; Grill, Joshua D.; Teng, Edmond] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Hsiao, Julia J.; Teng, Edmond] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Teng, E (reprint author), West Los Angeles VA Healthcare Ctr, Neurobehav Serv, 116AF,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM eteng@ucla.edu FU National Institute on Aging (NIA, AFAR, the John A. Haratford Foundation, the Atlantic Philanthropies, the Starr Foundation) [P50 AG16570, K23 AG028727, K08 AG34628]; Alzheimer's Disease Research Centers of California; Sidell-Kagan Foundation; NIA [U01 AG016976] FX Support from the National Institute on Aging [P50 AG16570, K23 AG028727 to P.H.L. and K08 AG34628 to E.T. (jointly sponsored by NIA, AFAR, the John A. Haratford Foundation, the Atlantic Philanthropies, the Starr Foundation, and an anonymous donor)], the Alzheimer's Disease Research Centers of California, and the Sidell-Kagan Foundation is acknowledged. The NACC database is funded by NIA (U01 AG016976). NR 50 TC 1 Z9 1 U1 1 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 EI 1421-9824 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2015 VL 39 IS 1-2 BP 12 EP 24 DI 10.1159/000365587 PG 13 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA AU5LZ UT WOS:000345649800002 PM 25300404 ER PT J AU Schultz, HY Dutz, JP Furukawa, F Goodfield, MJ Kuhn, A Lee, LA Nyberg, F Szepietowski, JC Sontheimer, RD Werth, VP AF Schultz, Heather Y. Dutz, Jan P. Furukawa, Fukumi Goodfield, Mark J. Kuhn, Annegret Lee, Lela A. Nyberg, Filippa Szepietowski, Jacek C. Sontheimer, Richard D. Werth, Victoria P. TI From Pathogenesis, Epidemiology, and Genetics to Definitions, Diagnosis, and Treatments of Cutaneous Lupus Erythematosus and Dermatomyositis: A Report from the 3rd International Conference on Cutaneous Lupus Erythematosus (ICCLE) 2013 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID QUALITY-OF-LIFE; REGENERATING MUSCLE; EUROPEAN-SOCIETY; CONTROLLED-TRIAL; MURINE MODEL; POLYMYOSITIS; MULTICENTER; EXPRESSION; HYDROXYCHLOROQUINE; ASSOCIATION C1 [Dutz, Jan P.] Univ British Columbia, Dept Dermatol & Skin Sci, Vancouver, BC V5Z 1M9, Canada. [Furukawa, Fukumi] Wakayama Med Univ, Dept Dermatol, Wakayama, Japan. [Goodfield, Mark J.] Leeds Gen Infirm, Dept Dermatol, Leeds, W Yorkshire, England. [Kuhn, Annegret] Univ Munster, Dept Dermatol, D-48149 Munster, Germany. [Lee, Lela A.] Univ Colorado, Dept Dermatol, Denver, CO 80202 USA. [Nyberg, Filippa] Danderyd Hosp, Karolinska Inst, Stockholm, Sweden. [Szepietowski, Jacek C.] Med Univ, Dept Dermatol Venereol & Allergol, Wroclaw, Poland. [Sontheimer, Richard D.] Univ Utah, Dept Dermatol, Salt Lake City, UT USA. [Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Werth, Victoria P.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Werth, VP (reprint author), Perelman Ctr Adv Med, Dept Dermatol, Suite 1-330A,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU Department of Veterans Affairs Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development; National Institutes of Health [NIH K24-AR 02207] FX We thank Sean Wood for great secretarial assistance and Advancing Innovation in Dermatology, Biogen, Celgene, Genzyme, Pfizer, Rigel, and Stiefel for supporting this meeting. Funds were used in part to support the work of HYS who summarized the meeting and wrote the initial draft of this communication. Support was also provided by the Department of Veterans Affairs Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development, and by the National Institutes of Health (NIH K24-AR 02207) to VPW. NR 36 TC 4 Z9 5 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2015 VL 135 IS 1 BP 7 EP 12 DI 10.1038/jid.2014.316 PG 6 WC Dermatology SC Dermatology GA AW4AX UT WOS:000346225000002 PM 25501376 ER PT J AU Jung, Y Tam, J Jalian, HR Anderson, RR Evans, CL AF Jung, Yookyung Tam, Joshua Jalian, H. Ray Anderson, R. Rox Evans, Conor L. TI Longitudinal, 3D In Vivo Imaging of Sebaceous Glands by Coherent Anti-Stokes Raman Scattering Microscopy: Normal Function and Response to Cryotherapy SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID PRACTICAL GUIDE; CARS MICROSCOPY; THERAPY FACTS; ACNE-VULGARIS; LABEL-FREE; CONTROVERSIES; SENSITIVITY; TISSUE; BRAIN; SKIN AB Sebaceous glands perform complex functions, and they are centrally involved in the pathogenesis of acne vulgaris. Current techniques for studying sebaceous glands are mostly static in nature, whereas the gland's main function excretion of sebum via the holocrine mechanism can only be evaluated over time. We present a longitudinal, real-time alternative-the in vivo, label-free imaging of sebaceous glands using Coherent Anti-Stokes Raman Scattering (CARS) microscopy, which is used to selectively visualize lipids. In mouse ears, CARS microscopy revealed dynamic changes in sebaceous glands during the holocrine secretion process, as well as in response to damage to the glands caused by cooling. Detailed gland structure, plus the active migration of individual sebocytes and cohorts of sebocytes, were measured. Cooling produced characteristic changes in sebocyte structure and migration. This study demonstrates that CARS microscopy is a promising tool for studying the sebaceous gland and its associated disorders in three dimensions in vivo. C1 [Jung, Yookyung; Tam, Joshua; Jalian, H. Ray; Anderson, R. Rox; Evans, Conor L.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Jung, Yookyung; Tam, Joshua; Anderson, R. Rox; Evans, Conor L.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Jalian, H. Ray] Univ Calif Los Angeles, Div Dermatol, Los Angeles, CA 90024 USA. RP Evans, CL (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM Evans.Conor@mgh.harvard.edu FU [R21CA53335]; [DP2 00007096] FX We thank Sunny Xie and Dan Fu of Harvard University for allowing the use of the Raman microscope. This study was funded, in part, by R21CA53335 (CLE) and a New Innovator Award (DP2 00007096, CLE). Information on the New Innovator Award Program is at http://nihroadmap.nih.gov/newinnovator/. NR 27 TC 7 Z9 7 U1 3 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2015 VL 135 IS 1 BP 39 EP 44 DI 10.1038/jid.2014.293 PG 6 WC Dermatology SC Dermatology GA AW4AX UT WOS:000346225000009 PM 25026458 ER PT J AU Hageman, MGJS Jayakumar, P King, JD Guitton, TG Doornberg, JN Ring, D AF Hageman, Michiel G. J. S. Jayakumar, Prakash King, John D. Guitton, Thierry G. Doornberg, Job N. Ring, David CA Sci Variation Grp TI The factors influencing the decision making of operative treatment for proximal humeral fractures SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Proximal humeral fractures; factors; decision-making; operative versus nonoperative treatment ID INTEROBSERVER RELIABILITY; CLASSIFICATION; AGREEMENT AB Background: The factors influencing the decision making of operative treatment for fractures of the proximal humerus are debated. We hypothesized that there is no difference in treatment recommendations between surgeons shown radiographs alone and those shown radiographs and patient information. Secondarily, we addressed (1) factors associated with a recommendation for operative treatment, (2) factors associated with recommendation for arthroplasty, (3) concordance with the recommendations of the treating surgeons, and (4) factors affecting the inter-rater reliability of treatment recommendations. Methods: A total of 238 surgeons of the Science of Variation Group rated 40 radiographs of patients with proximal humerus fractures. Participants were randomized to receive information about the patient and mechanism of injury. The response variables included the choice of treatment (operative vs nonoperative) and the percentage of matches with the actual treatment. Results: Participants who received patient information recommended operative treatment less than those who received no information. The patient information that had the greatest influence on treatment recommendations included age (55%) and fracture mechanism (32%). The only other factor associated with a recommendation for operative treatment was region of practice. There was no significant difference between participants who were and were not provided with information regarding agreement with the actual treatment (operative vs nonoperative) provided by the treating surgeon. Conclusion: Patient informatio-older age in particular-is associated with a higher likelihood of recommending nonoperative treatment than radiographs alone. Clinical information did not improve agreement of the Science of Variation Group with the actual treatment or the generally poor interobserver agreement on treatment recommendations. (C) 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. C1 [Hageman, Michiel G. J. S.; Jayakumar, Prakash; King, John D.] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Guitton, Thierry G.; Doornberg, Job N.] Acad Med Ctr Amsterdam, Amsterdam, Netherlands. [Ring, David] Massachusetts Gen Hosp, Yawkey Ctr, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Chief Orthopaed Hand Serv, Ste 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Guitton, Thierry/0000-0002-2599-1985; Ring, David/0000-0002-6506-4879; Soong, Maximillian/0000-0003-0333-8181 FU Marti-Keunig Eckhart Stichting; Anna Foundation; Spinoza Foundation FX Michiel G.J.S. Hageman is supported by Dutch research grants from Marti-Keunig Eckhart Stichting, Anna Foundation, and Spinoza Foundation. NR 13 TC 3 Z9 3 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD JAN PY 2015 VL 24 IS 1 BP E21 EP E26 DI 10.1016/j.jse.2014.05.013 PG 6 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA AU5MN UT WOS:000345651300004 PM 25168346 ER PT J AU Hyams, ES Monga, M Pearle, MS Antonelli, JA Semins, MJ Assimos, DG Lingeman, JE Pais, VM Preminger, GM Lipkin, ME Eisner, BH Shah, O Sur, RL Mufarrij, PW Matlagak, BR AF Hyams, Elias S. Monga, Manoj Pearle, Margaret S. Antonelli, Jodi A. Semins, Michelle J. Assimos, Dean G. Lingeman, James E. Pais, Vernon M., Jr. Preminger, Glenn M. Lipkin, Michael E. Eisner, Brian H. Shah, Ojas Sur, Roger L. Mufarrij, Patrick W. Matlagak, Brian R. TI A Prospective, Multi-Institutional Study of Flexible Ureteroscopy for Proximal Ureteral Stones Smaller than 2 cm SO JOURNAL OF UROLOGY LA English DT Article DE ureter; kidney; calculi; ureteroscopy; diagnostic imaging ID SHOCK-WAVE LITHOTRIPSY; URINARY-TRACT CALCULI; MANAGEMENT; TOMOGRAPHY AB Purpose: Flexible ureteroscopy is rapidly becoming a first line therapy for many patients with renal and ureteral stones. However, current understanding of treatment outcomes in patients with isolated proximal ureteral stones is limited. Therefore, we performed a prospective, multi-institutional study of ureteroscopic management of proximal ureteral stones smaller than 2 cm to better define clinical outcomes associated with this approach. Materials and Methods: Adult patients with proximal ureteral calculi smaller than 2 cm were prospectively identified. Patients with concomitant ipsilateral renal calculi or prior ureteral stenting were excluded from study. Flexible ureteroscopy, holmium laser lithotripsy and ureteral stent placement was performed. Ureteral access sheath use, laser settings and other details of perioperative and postoperative management were based on individual surgeon preference. Stone clearance was determined by the results of renal ultrasound and plain x-ray of the kidneys, ureters and bladder 4 to 6 weeks postoperatively. Results: Of 71 patients 44 (62%) were male and 27 (38%) were female. Mean age was 48.2 years. ASA (R) score was 1 in 12 cases (16%), 2 in 41 (58%), 3 in 16 (23%) and 4 in 2 (3%). Mean body mass index was 31.8 kg/m(2), mean stone size was 7.4 mm (range 5 to 15) and mean operative time was 60.3 minutes (range 15 to 148). Intraoperative complications occurred in 2 patients (2.8%), including mild ureteral trauma. Postoperative complications developed in 6 patients (8.7%), including urinary tract infection in 3, urinary retention in 2 and flash pulmonary edema in 1. The stone-free rate was 95% and for stones smaller than 1 cm it was 100%. Conclusions: Flexible ureteroscopy is associated with excellent clinical outcomes and acceptable morbidity when applied to patients with proximal ureteral stones smaller than 2 cm. C1 [Hyams, Elias S.; Pais, Vernon M., Jr.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Monga, Manoj] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Pearle, Margaret S.; Antonelli, Jodi A.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Semins, Michelle J.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Assimos, Dean G.] Univ Alabama Birmingham, Birmingham, AL USA. [Lingeman, James E.] Indiana Univ Hlth, Indianapolis, IN USA. [Preminger, Glenn M.; Lipkin, Michael E.] Duke Univ, Med Ctr, Durham, NC USA. [Eisner, Brian H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shah, Ojas] NYU, Langone Med Ctr, New York, NY USA. [Sur, Roger L.] Univ Calif San Diego, San Diego, CA 92103 USA. [Mufarrij, Patrick W.] George Washington Univ, Med Ctr, Washington, DC 20037 USA. [Matlagak, Brian R.] Johns Hopkins Med Inst, Baltimore, MD 21287 USA. RP Matlagak, BR (reprint author), Johns Hopkins Med Inst, 600 North Wolfe St,Pk 221, Baltimore, MD 21287 USA. EM bmatlaga@jhmi.edu FU NIDDK NIH HHS [P01 DK043881, P01 DK056788] NR 18 TC 19 Z9 20 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD JAN PY 2015 VL 193 IS 1 BP 165 EP 169 DI 10.1016/j.juro.2014.07.002 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA AW3FL UT WOS:000346171500042 PM 25014576 ER PT J AU Nasser, NJ Na'amad, M Weinberg, I Gabizon, AA AF Nasser, Nicola J. Na'amad, Mira Weinberg, Ido Gabizon, Alberto A. TI Pharmacokinetics of low molecular weight heparin in patients with malignant tumors SO ANTI-CANCER DRUGS LA English DT Article DE cancer; coagulation; enoxaparin; heparanase; heparin; pharmacokinetics ID CELL LUNG-CANCER; VENOUS THROMBOEMBOLISM; MAMMALIAN HEPARANASE; SPLICE VARIANT; GENE CLONING; EXPRESSION; METASTASIS; SURVIVAL; SULFATE; ANTICOAGULATION AB Cancer patients have an increased risk for venous thromboembolism (VTE). Low molecular weight heparin (LMWH) is the mainstay of VTE treatment in these patients. Heparanase, which degrades heparin and LMWH, is an enzyme secreted from a variety of malignant tumors. The objective of this study was to elucidate the pharmacokinetics of LMWH in patients with locally advanced or metastatic cancer. A total of 10 cancer patients with VTE treated with the LMWH enoxaparin at a standard dose of 1 mg/kg every 12 h were enrolled. Blood samples were obtained before the injection of LMWH and at 1, 2, 3, 4, 6, and 8 h after LMWH administration, and they were tested for anti-factor Xa activity and heparanase levels. Peak anti-Xa activity was achieved 2-8 h after subcutaneous administration of LMWH. Six patients did not reach a therapeutic anti-Xa activity target (0.6-1.2 IU/ml) at 4 h after LMWH administration. Four patients did not reach anti-factor Xa values of 0.6 IU/ml throughout the trial. The median anti-Xa activity before LMWH injection was 0.24 IU/ml (range 0.07-0.7 IU/ml), as opposed to 0.52 IU/ml in historical controls. The median anti-Xa activity 4 h after LMWH injection was 0.58 IU/ml (range 0.22-1.23 IU/ml), as opposed to 1.2 IU/ml in historical controls. The blood level of heparanase in patients with malignancy and VTE was 6.24 +/- 4.3 ng/ml, compared with 2.67 +/- 1.09 ng/ml in cancer-free, age-matched, normal controls. In this pilot study, a substantial proportion of cancer patients suffering from VTE and treated with LMWH had subtherapeutic anti-Xa activity. Anti-Cancer Drugs 26:106-111 (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Nasser, Nicola J.] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10065 USA. [Weinberg, Ido] Massachusetts Gen Hosp, Inst Heart Vasc & Stroke Care, Boston, MA 02114 USA. [Na'amad, Mira] Shaare Zedek Med Ctr, Blood Bank, Jerusalem, Israel. [Na'amad, Mira] Shaare Zedek Med Ctr, Hematol Lab, Jerusalem, Israel. [Gabizon, Alberto A.] Shaare Zedek Med Ctr, Dept Oncol, Jerusalem, Israel. [Gabizon, Alberto A.] Shaare Zedek Med Ctr, Dept Hematol, Jerusalem, Israel. [Gabizon, Alberto A.] Hebrew Univ Jerusalem, Hadassah Med Sch, Fac Med, IL-91010 Jerusalem, Israel. RP Nasser, NJ (reprint author), Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, 1275 York Ave, New York, NY 10065 USA. EM nassern@mskcc.org FU Israeli Cancer Association FX The study was funded by a research grant from the Israeli Cancer Association (grant to N.J.N.). NR 33 TC 1 Z9 1 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4973 EI 1473-5741 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD JAN PY 2015 VL 26 IS 1 BP 106 EP 111 DI 10.1097/CAD.0000000000000176 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA AU4HS UT WOS:000345572000012 PM 25280062 ER PT J AU Goral, M Campanelli, L Spiro, A AF Goral, Mira Campanelli, Luca Spiro, Avron, III TI Language dominance and inhibition abilities in bilingual older adults SO BILINGUALISM-LANGUAGE AND COGNITION LA English DT Article DE bilingual; dominant; aging; inhibition ID AGE-RELATED DECLINE; EXECUTIVE CONTROL; SENTENCE COMPREHENSION; COGNITIVE CONTROL; WORKING-MEMORY; LEXICAL ACCESS; SIMON TASK; ADVANTAGE; ATTENTION; INTERFERENCE AB This study aimed to examine the so-called bilingual advantage in older adults' performance in three cognitive domains and to identify whether language use and bilingual type (dominant vs. balanced) predicted performance. The participants were 106 Spanish-English bilinguals ranging in age from 50 years to 84 years. Three cognitive domains were examined (each by a single test): inhibition (the Simon task), alternating attention (the Trail Making test), and working memory (Month Ordering). The data revealed that age was negatively correlated to performance in each domain. Bilingual type - balanced vs. dominant - predicted performance and interacted with age only on the inhibition measure (the Simon task). Balanced bilinguals showed age-related inhibition decline (i.e., greater Simon effect with increasing age); in contrast, dominant bilinguals showed little or no age-related change. The findings suggest that bilingualism may offer cognitive advantage in older age only for a subset of bilinguals. C1 [Goral, Mira] CUNY Herbert H Lehman Coll, Bronx, NY 10468 USA. [Goral, Mira; Campanelli, Luca] CUNY, Grad Ctr, New York, NY USA. [Spiro, Avron, III] VA Boston Healthcare Syst, Boston, MA USA. [Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Spiro, Avron, III] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Goral, M (reprint author), CUNY Herbert H Lehman Coll, Speech Bldg,Room 227,250 Bedford Pk Blvd, Bronx, NY 10468 USA. EM mira.goral@lehman.cuny.edu OI Campanelli, Luca/0000-0001-6035-0545 FU NIA NIH HHS [R01 AG014345, R03 AG027532]; NIDCD NIH HHS [SC1 DC009792] NR 59 TC 5 Z9 5 U1 2 U2 15 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1366-7289 EI 1469-1841 J9 BILING-LANG COGN JI Biling.-Lang. Cogn. PD JAN PY 2015 VL 18 IS 1 BP 79 EP 89 DI 10.1017/S1366728913000126 PG 11 WC Linguistics; Psychology, Experimental SC Linguistics; Psychology GA AU4KY UT WOS:000345581000016 PM 27531968 ER PT J AU Agarwala, A Jones, P Nambi, V AF Agarwala, Anandita Jones, Peter Nambi, Vijay TI The Role of Antisense Oligonucleotide Therapy in Patients with Familial Hypercholesterolemia: Risks, Benefits, and Management Recommendations SO CURRENT ATHEROSCLEROSIS REPORTS LA English DT Article DE Familial hypercholesterolemia; LDL cholesterol; ASO; Antisense oligonucleotide therapy; Mipomersen ID DENSITY-LIPOPROTEIN CHOLESTEROL; ASSOCIATION EXPERT PANEL; PLACEBO-CONTROLLED TRIAL; CORONARY-HEART-DISEASE; B SYNTHESIS INHIBITION; APOLIPOPROTEIN-B; ANDROGEN RECEPTOR; LDL CHOLESTEROL; PROSTATE-CANCER; MIPOMERSEN AB Antisense oligonucleotide therapy is a promising approach for the treatment of a broad variety of medical conditions. It functions at the cellular level by interfering with RNA function, often leading to degradation of specifically targeted abnormal gene products implicated in the disease process. Mipomersen is a novel antisense oligonucleotide directed at apolipoprotein (apoB)-100, the primary apolipoprotein associated with low-density lipoprotein cholesterol (LDL-C), which has recently been approved for the treatment of familial hypercholesterolemia. A number of clinical studies have demonstrated its efficacy in lowering LDL-C and apoB levels in patients with elevated LDL-C despite maximal medical therapy using conventional lipid-lowering agents. This review outlines the risks and benefits of therapy and provides recommendations on the use of mipomersen. C1 [Agarwala, Anandita] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. [Jones, Peter; Nambi, Vijay] Baylor Coll Med, Methodist DeBakey Heart & Vasc Ctr, Ctr Cardiovasc Dis Prevent, Dept Med, Houston, TX 77030 USA. RP Nambi, V (reprint author), Baylor Coll Med, Methodist DeBakey Heart & Vasc Ctr, Ctr Cardiovasc Dis Prevent, Dept Med, 6565 Fannin St,STE B 160, Houston, TX 77030 USA. EM anandita.kulkarni@bcm.edu; jones@bcm.edu; vnambi@bcm.edu FU Sanofi; Gillson Longenbaugh Foundation; Gulf Coast Regional Foundation; Methodist Hospital Research institute; NIH/ NHLBI K23 FX Vijay Nambi has a provisional patent on the use of biomarkers in heart failure with Roche; research collaboration with GE; received personal fees from Sanofi for serving on the regional advisory board; received grants from Gillson Longenbaugh Foundation, Gulf Coast Regional Foundation, Methodist Hospital Research institute, and NIH/ NHLBI K23; national monitor for Anthera and research collaboration with Tomtec. NR 45 TC 5 Z9 5 U1 0 U2 5 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1523-3804 EI 1534-6242 J9 CURR ATHEROSCLER REP JI Curr. Atheroscleros. Rep. PD JAN PY 2015 VL 17 IS 1 AR 467 DI 10.1007/s11883-014-0467-4 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AU0NZ UT WOS:000345321300003 PM 25398643 ER PT J AU Hanson, AJ Craft, S Banks, WA AF Hanson, Angela J. Craft, Suzanne Banks, William A. TI The APOE Genotype: Modification of Therapeutic Responses in Alzheimer's Disease SO CURRENT PHARMACEUTICAL DESIGN LA English DT Article DE Alzheimer's disease; treatments; APOE genotype ID APOLIPOPROTEIN-E GENOTYPE; MILD COGNITIVE IMPAIRMENT; AMYLOID-BETA; INTRANASAL INSULIN; LOWERING TREATMENT; EPSILON-4 ALLELE; OLDER-ADULTS; DOUBLE-BLIND; VITAMIN-E; DEMENTIA AB The translation of promising preclinical treatments into effective drugs for Alzheimer's disease (AD) has been challenging. One of the most potent risk factors for sporadic AD is carrier status of the epsilon 4 allele of the apolipoprotein E gene (E4). E4 carriers show a differential response to several therapies which are being investigated as AD treatments, including acetylcholinesterase inhibitors and therapeutics with vascular and metabolic targets. The differential treatment responses of E4 carriers may partially explain why some treatments show a null effect in clinical trials. Understanding the reasons behind these responses is not only important for clinical practice, but may also help us elucidate mechanisms for this neurodegenerative disease. C1 [Hanson, Angela J.; Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Hanson, Angela J.; Banks, William A.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Craft, Suzanne] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA. RP Hanson, AJ (reprint author), 325 9th Ave,Box 359755, Seattle, WA 98104 USA. EM hansonaj@uw.edu NR 73 TC 6 Z9 6 U1 3 U2 20 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2015 VL 21 IS 1 BP 114 EP 120 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AU2GM UT WOS:000345434600011 PM 25330331 ER PT J AU Fossati, N Trinh, QD Sammon, J Sood, A Larcher, A Sun, M Karakiewicz, P Guazzoni, G Montorsi, F Briganti, A Menon, M Abdollah, F AF Fossati, Nicola Quoc-Dien Trinh Sammon, Jesse Sood, Akshay Larcher, Alessandro Sun, Maxine Karakiewicz, Pierre Guazzoni, Giorgio Montorsi, Francesco Briganti, Alberto Menon, Mani Abdollah, Firas TI Identifying Optimal Candidates for Local Treatment of the Primary Tumor Among Patients Diagnosed with Metastatic Prostate Cancer: A SEER-based Study SO EUROPEAN UROLOGY LA English DT Article DE Prostate cancer; Metastasis; Primary tumor treatment; Radical prostatectomy; Radiation therapy; Cancer-specific survival ID NICHE AB A recent study observed a survival benefit in men diagnosed with metastatic prostate cancer (mPCa) and managed with local treatment of the primary tumor (LT; either radical prostatectomy plus pelvic lymph node dissection or radiation therapy). We tested the hypothesis that only specific mPCa patients would benefit from LT and that the potential benefit would vary based on primary tumor characteristics. A total of 8197 mPCa patients at diagnosis(M1a, M1b, and M1c) were identified using the Surveillance Epidemiology and End Results database (2004-2011) and were divided according to treatment type: LT versus nonlocal treatment of the primary tumor (NLT; either androgen deprivation therapy or observation). Multivariable Cox regression analysis was used to predict cancer-specific mortality (CSM) in patients that received NLT. To assess whether the benefit of LT was different by baseline risk, we tested an interaction with CSM risk and LT. At multivariable analysis, all predictors were significantly associated with CSM, and the interaction test was statistically significant (p < 0.0001). Local treatment of the primary tumor, compared with NLT, conferred a higher CSM-free survival rate in patients with a predicted CSM risk <40%. The number needed to treat according to the predicted CSM risk at 3 yr after diagnosis remained substantially constant from 10% to 30%, whereas it exponentially increased for predicted CSM risk >40%. These results should serve as a foundation for future prospective trials. Patient summary: Among metastatic prostate cancer patients, the potential benefit of local treatment to the primary tumor depends greatly on tumor characteristics, and patient selection is essential to avoid either over-or undertreatment. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Fossati, Nicola] Mem Sloan Kettering Canc Ctr, Dept Biostat & Epidemiol, New York, NY 10021 USA. [Fossati, Nicola; Larcher, Alessandro; Guazzoni, Giorgio; Montorsi, Francesco; Briganti, Alberto] Osped San Raffaele, IRCCS, URI, Div Oncol,Unit Urol, Milan, Italy. [Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Sammon, Jesse; Sood, Akshay; Menon, Mani; Abdollah, Firas] Henry Ford Hosp, Vattikuti Urol Inst, Detroit, MI 48202 USA. [Sammon, Jesse; Sood, Akshay; Menon, Mani; Abdollah, Firas] Henry Ford Hosp, VUI Ctr Outcomes Res Analyt & Evaluat, Detroit, MI 48202 USA. [Larcher, Alessandro; Sun, Maxine; Karakiewicz, Pierre] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada. RP Abdollah, F (reprint author), Henry Ford Hosp, Vattikuti Urol Inst, Ctr Outcomes Res Analyt & Evaluat, 2799 W Grand Blvd, Detroit, MI 48202 USA. EM firas.abdollah@gmail.com OI Guazzoni, Giorgio Ferruccio/0000-0002-5713-8313; Fossati, Nicola/0000-0002-6816-3725; Larcher, Alessandro/0000-0002-5005-589X NR 9 TC 26 Z9 27 U1 3 U2 7 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 2015 VL 67 IS 1 BP 3 EP 6 DI 10.1016/j.eururo.2014.08.056 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA AU4YY UT WOS:000345615400003 PM 25217422 ER PT J AU Orsola, A Bellmunt, J AF Orsola, Anna Bellmunt, Joaquim TI The "Artificial'' Docetaxel Space: The Evolving Treatment Paradigm of Metastatic Castration-Resistant Prostate Cancer SO EUROPEAN UROLOGY LA English DT Editorial Material ID ENZALUTAMIDE C1 [Orsola, Anna] Bladder Canc Ctr DFCI, Boston, MA USA. [Bellmunt, Joaquim] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Bellmunt, Joaquim] Univ Hosp Del Mar IMIM, Barcelona, Spain. RP Bellmunt, J (reprint author), Dana Farber Brigham & Womens Canc Ctr, Bladder Canc Ctr, 450 Brookline Ave, Boston, MA 02215 USA. EM joaquim_bellmunt@dfci.harvard.edu NR 9 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD JAN PY 2015 VL 67 IS 1 BP 30 EP 32 DI 10.1016/j.eururo.2014.07.030 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA AU4YY UT WOS:000345615400010 PM 25108578 ER PT J AU Albiges, L Choueiri, T Escudier, B Galsky, M George, D Hofmann, F Lam, T Motzer, R Mulders, P Porta, C Powles, T Sternberg, C Bex, A AF Albiges, Laurence Choueiri, Toni Escudier, Bernard Galsky, Matthew George, Dan Hofmann, Fabian Lam, Thomas Motzer, Robert Mulders, Peter Porta, Camillo Powles, Thomas Sternberg, Cora Bex, Axel TI A Systematic Review of Sequencing and Combinations of Systemic Therapy in Metastatic Renal Cancer SO EUROPEAN UROLOGY LA English DT Review DE Renal cell carcinoma; Tyrosine kinase inhibitor; Sequence of systemic therapies; Combination of systemic therapies ID PHASE-III TRIAL; RANDOMIZED DISCONTINUATION TRIAL; CELL CARCINOMA PATIENTS; VEGF-TARGETED THERAPY; INTERFERON-ALPHA; DOUBLE-BLIND; SORAFENIB; BEVACIZUMAB; TEMSIROLIMUS; SUNITINIB AB Context: The introduction of novel molecular-targeted agents has revolutionised the management of patients with metastatic renal cell carcinoma (mRCC). However, uncertainties remain over sequential or simultaneous combination therapies. Objective: To systematically review relevant literature comparing the clinical effectiveness and harms of different sequencing and combinations of systemic targeted therapies for mRCC. Evidence acquisition: Relevant databases (including Medline, Cochrane Library, trial registries, and conference proceedings) were searched (January 2000 to September 2013) including only randomised controlled trials (RCTs). Risk of bias assessment was performed. A qualitative and quantitative synthesis of the evidence was presented. Evidence synthesis: The literature search identified 5149 articles. A total of 24 studies reporting on 9589 patients were eligible for inclusion; data from four studies were included for meta-analysis. There were generally low risks of bias across studies; however, clinical and methodological heterogeneity prevented pooling of data for most studies. Overall, the data showed several targeted therapies were associated with an improvement in progression-free survival in patients with mRCC. There were limited data from RCTs regarding the issue of sequencing; studies on combination therapies have been hampered by difficulties with tolerability and safety. Conclusions: Although the role of vascular endothelial growth factor/vascular endothelial growth factor receptor targeting therapies and mammalian target of rapamycin inhibition in the management of mRCC is now established, limited reliable data are available regarding sequencing and combination therapies. Although data from retrospective cohort studies suggest a potential benefit for sequencing systemic therapies, significant uncertainties remain. Presently, mRCC systemic treatment should follow international guidelines (such as the European Society for Medical Oncology, National Comprehensive Cancer Network, and European Association of Urology) for patients fit to receive several lines of systemic therapies. Patient summary: We thoroughly examined the literature on the benefits and harms of combining drugs for the treatment of kidney cancer that has spread and on the sequence in which the drugs should be given. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Albiges, Laurence; Escudier, Bernard] Inst Gustave Roussy, F-94805 Villejuif, France. [Choueiri, Toni] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Galsky, Matthew] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA. [George, Dan] Duke Univ, Med Ctr, Durham, NC USA. [Hofmann, Fabian] Sunderby Hosp, Dept Urol, Sunderby, Sweden. [Lam, Thomas] Univ Aberdeen, Acad Urol Unit, Aberdeen, Scotland. [Motzer, Robert] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Mulders, Peter] Radboud Univ Nijmegen, Dept Urol, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Porta, Camillo] IRCCS San Matteo Univ Hosp Fdn, Pavia, Italy. [Powles, Thomas] Barts Canc Inst, London, England. [Sternberg, Cora] San Camillo & Forlanini Hosp Padiglione Flajani, Dept Med Oncol, Rome, Italy. [Bex, Axel] Netherlands Canc Inst, Div Surg Oncol, Dept Urol, Amsterdam, Netherlands. RP Albiges, L (reprint author), Inst Gustave Roussy, 114 Rue Edouard Vaillant, F-94805 Villejuif, France. EM laurence.albiges@gustaveroussy.fr RI Mulders, Peter/H-8076-2014; OI Porta, Camillo/0000-0003-2412-1563 FU Pfizer; Novartis; Bayer; GlaxoSmithKline FX Laurence Albiges certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Laurence Albiges received research grants from Pfizer and Novartis, and she has participated on the advisory boards at Novartis, Pfizer, Amgen, and Sanofi. She has received honoraria from Novartis and Pfizer. Toni Choueiri received a research grant from Pfizer and has participated on the advisory boards at Pfizer, GSK, Bayer, Aveo, and Novartis. Bernard Escudier has had a consultant or advisory board role with Bayer Pharma, Pfizer, and Novartis; he has received honoraria from Bayer, Roche, Pfizer, Genentech, Novartis, Aveo, and GSK. Matthew Galsky received research funding from Novartis; he has participated on the advisory boards at Janssen, Astellas/Medivation, and Dendreon; he has equity in Dual Therapeutics LLC. Dan George has had a consultancy role with and/or received honoraria or research funding from Bayer, Novartis, and Pfizer. Fabian Hofmann has no conflicts of interest to disclose. Thomas Lam has no conflicts of interest to disclose. Robert J. Motzer has received research funding from Novartis, Pfizer, and GlaxoSmithKline, has consulted for Bayer and Pfizer, and has provided paid expert testimony for Pfizer. Peter Mulders has participated on the advisory boards at Bayer, GSK, Pfizer, and Novartis. Camillo Porta has participated on the advisor boards and/or had a speaker role at Pfizer, GSK, Bayer-Schering, Novartis, Astellas, Aveo, and Boehringer-Ingelheim; he has received research grants from Pfizer. Thomas Powles has received research funding and participated on the speakers' bureau for Pfizer, GSK, Novartis, and Bayer. Cora N. Sternberg has received honoraria from Novartis, Pfizer, and GlaxoSmithKline. Axel Bex has participated on the advisory boards at Pfizer, Bayer, GSK, and Novartis. He is the principal investigator of the EORTC SURTIME trial, supported in part by an educational grant from Pfizer. NR 54 TC 40 Z9 41 U1 4 U2 19 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 2015 VL 67 IS 1 BP 100 EP 110 DI 10.1016/j.eururo.2014.04.006 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA AU4YY UT WOS:000345615400024 PM 24841777 ER PT J AU Campbell, SL Robel, S Cuddapah, VA Robert, S Buckingham, SC Kahle, KT Sontheimer, H AF Campbell, Susan L. Robel, Stefanie Cuddapah, Vishnu A. Robert, Stephanie Buckingham, Susan C. Kahle, Kristopher T. Sontheimer, Harald TI GABAergic Disinhibition and Impaired KCC2 Cotransporter Activity Underlie Tumor-Associated Epilepsy SO GLIA LA English DT Article DE glioma; GABA; peritumoral epilepsy; KCC2 ID PRIMARY BRAIN-TUMORS; TEMPORAL-LOBE EPILEPSY; HUMAN GLIOMA-CELLS; GABA(A) RECEPTOR; MALIGNANT GLIOMAS; GLUTAMATE RELEASE; SEIZURES; HIPPOCAMPUS; NEURONS; CORTEX AB Seizures frequently accompany gliomas and often escalate to peritumoral epilepsy. Previous work revealed the importance of tumor-derived excitatory glutamate (Glu) release mediated by the cystine-glutamate transporter (SXC) in epileptogenesis. We now show a novel contribution of GABAergic disinhibition to disease pathophysiology. In a validated mouse glioma model, we found that peritumoral parvalbumin-positive GABAergic inhibitory interneurons are significantly reduced, corresponding with deficits in spontaneous and evoked inhibitory neurotransmission. Most remaining peritumoral neurons exhibit elevated intracellular Cl- concentration ([Cl-](i)) and consequently depolarizing, excitatory gamma-aminobutyric acid (GABA) responses. In these neurons, the plasmalemmal expression of KCC2, which establishes the low [Cl-](i) required for GABA(A)R-mediated inhibition, is significantly decreased. Interestingly, reductions in inhibition are independent of Glu release, but the presence of both decreased inhibition and decreased SXC expression is required for epileptogenesis. We suggest GABAergic disinhibition renders peritumoral neuronal networks hyper-excitable and susceptible to seizures triggered by excitatory stimuli, and propose KCC2 as a therapeutic target. GLIA 2015;63:23-36 Main Points In a mouse model of glioma peritumoral epilepsy, we show that peritumoral cortex contained fewer PV-positive GABAergic interneurons and elevated [Cl-](i) leading to depolarizing GABA responses and reduced inhibition in peritumoral neurons. C1 [Campbell, Susan L.; Robel, Stefanie; Cuddapah, Vishnu A.; Robert, Stephanie; Buckingham, Susan C.; Sontheimer, Harald] Univ Alabama Birmingham, Dept Neurobiol, Ctr Glial Biol Med, Birmingham, AL 35294 USA. [Kahle, Kristopher T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Cambridge, MA 02138 USA. [Kahle, Kristopher T.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA USA. RP Sontheimer, H (reprint author), Univ Alabama Birmingham, Dept Neurobiol, 1719 6th Ave S,CIRC 425, Birmingham, AL 35294 USA. EM sontheimer@uab.edu OI Sontheimer, Harald/0000-0002-5843-9871 FU NIH [2R01-NS052634, 5R01-NS036692, 5T32NS048039-03] FX Grant sponsor: NIH; Grant numbers: 2R01-NS052634; 5R01-NS036692; 5T32NS048039-03. NR 49 TC 19 Z9 19 U1 0 U2 23 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-1491 EI 1098-1136 J9 GLIA JI Glia PD JAN PY 2015 VL 63 IS 1 BP 23 EP 36 DI 10.1002/glia.22730 PG 14 WC Neurosciences SC Neurosciences & Neurology GA AU0XC UT WOS:000345344500002 PM 25066727 ER PT J AU Wang, X Lopez, OL Sweet, RA Becker, JT DeKosky, ST Barmada, MM Demirci, FY Kamboh, MI AF Wang, Xingbin Lopez, Oscar L. Sweet, Robert A. Becker, James T. DeKosky, Steven T. Barmada, Mahmud M. Demirci, F. Yesim Kamboh, M. Ilyas TI Genetic Determinants of Disease Progression in Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease progression; genome-wide association studies; late-onset Alzheimer's disease; Mini-Mental State Examination ID GENOME-WIDE ASSOCIATION; SYNDROME TYPE-I; IDENTIFIES VARIANTS; COMMON VARIANTS; BRAIN ATROPHY; PAX3; POPULATION; MUTATIONS; CD2AP; EPHA1 AB There is a strong genetic basis for late-onset Alzheimer's disease (LOAD); thus far 22 genes/loci have been identified that affect the risk of LOAD. However, the relationships among the genetic variations at these loci and clinical progression of the disease have not been fully explored. In the present study, we examined the relationships of 22 known LOAD genes to the progression of AD in 680 AD patients recruited from the University of Pittsburgh Alzheimer's Disease Research Center. Patients were classified as "rapid progressors" if the Mini-Mental State Examination (MMSE) changed >= 3 points in 12 months and "slow progressors" if the MMSE changed <= 2 points. We also performed a genome-wide association study in this cohort in an effort to identify new loci for AD progression. Association analysis between single nucleotide polymorphisms (SNPs) and the progression status of the AD cases was performed using logistic regression model controlled for age, gender, dementia medication use, psychosis, and hypertension. While no significant association was observed with either APOE*4 (p = 0.94) or APOE*2 (p = 0.33) with AD progression, we found multiple nominally significant associations (p < 0.05) either within or adjacent to seven known LOAD genes (INPP5D, MEF2C, TREM2, EPHA1, PTK2B, FERMT2, and CASS4) that harbor both risk and protective SNPs. Genome-wide association analyses identified four suggestive loci (PAX3, CCRN4L, PIGQ, and ADAM19) at p < 1E-05. Our data suggest that short-term clinical disease progression in AD has a genetic basis. Better understanding of these genetic factors could help to improve clinical trial design and potentially affect the development of disease modifying therapies. C1 [Wang, Xingbin; Barmada, Mahmud M.; Demirci, F. Yesim; Kamboh, M. Ilyas] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15261 USA. [Wang, Xingbin] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. [Lopez, Oscar L.; Sweet, Robert A.; Becker, James T.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15261 USA. [Lopez, Oscar L.; Sweet, Robert A.; Becker, James T.; Kamboh, M. Ilyas] Univ Pittsburgh, Alzheimers Dis Res Ctr, Pittsburgh, PA 15261 USA. [Sweet, Robert A.; Kamboh, M. Ilyas] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15261 USA. [DeKosky, Steven T.] Univ Virginia, Sch Med, Dept Neurol, Charlottesville, VA 22908 USA. [Sweet, Robert A.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 4, Pittsburgh, PA USA. RP Kamboh, MI (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. EM kamboh@pitt.edu OI Demirci, F. Yesim/0000-0001-6907-9843; Kamboh, M. Ilyas/0000-0002-3453-1438; Barmada, M Michael/0000-0002-3604-6460 FU National Institutes of Health [AG030653, AG041718, AG005133, AG027224] FX This study was supported by the National Institutes of Health grants AG030653, AG041718, AG005133, and AG027224. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs, the National Institutes of Health, or the United States Government. NR 37 TC 9 Z9 10 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 2015 VL 43 IS 2 BP 649 EP 655 DI 10.3233/JAD-140729 PG 7 WC Neurosciences SC Neurosciences & Neurology GA AU2NM UT WOS:000345455300027 PM 25114068 ER PT J AU Kieran, MW AF Kieran, Mark W. TI Time to Rethink the Unthinkable: Upfront Biopsy of Children With Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG) SO PEDIATRIC BLOOD & CANCER LA English DT Article ID ACTIVATING ACVR1 MUTATIONS C1 [Kieran, Mark W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Kieran, Mark W.] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA 02215 USA. RP Kieran, MW (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave,Rm D-3154, Boston, MA 02215 USA. EM mark_kieran@dfci.harvard.edu OI Kieran, Mark/0000-0003-2184-7692 NR 9 TC 11 Z9 11 U1 0 U2 2 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 2015 VL 62 IS 1 BP 3 EP 4 DI 10.1002/pbc.25266 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA AU0NG UT WOS:000345319300002 PM 25284709 ER PT J AU Voss, SD Glade-Bender, J Spunt, SL DuBois, SG Widemann, BC Park, JR Leary, SES Nelson, MD Adamson, PC Blaney, SM Weigel, B AF Voss, Stephan D. Glade-Bender, Julia Spunt, Sheri L. DuBois, Steven G. Widemann, Brigitte C. Park, Julie R. Leary, Sarah E. S. Nelson, Marvin D. Adamson, Peter C. Blaney, Susan M. Weigel, Brenda TI Growth Plate Abnormalities in Pediatric Cancer Patients Undergoing Phase 1 Anti-Angiogenic Therapy: A Report From the Children's Oncology Group Phase I Consortium SO PEDIATRIC BLOOD & CANCER LA English DT Article DE anti-angiogenic therapy; developing growth plate; physeal toxicity ID REFRACTORY SOLID TUMORS; SKELETAL RADIOGRAPHIC CHANGES; SAFETY EVALUATION; TRIAL; VEGF; BEVACIZUMAB; NEUROBLASTOMA; RECEPTORS; SUNITINIB; ADOLESCENTS AB BackgroundPre-clinical studies suggest that anti-angiogenic agents may be toxic to the developing growth plate. The purpose of this study was to evaluate the incidence of growth plate abnormalities in children with refractory cancer undergoing anti-angiogenic therapy. ProcedureTargeted radiographic studies from 53 subjects enrolled on six separate Children's Oncology Group Phase 1 and Pilot Consortium clinical trials evaluating new anti-cancer agents interfering with angiogenesis were reviewed. Subjects received tyrosine kinase inhibitors with anti-angiogenic effects (n=35), monoclonal antibodies targeting vascular endothelial growth factor (VEGF) (n=13), or angiopoietin (n=5). Radiographs of their distal femur/proximal tibia were obtained at baseline. Follow-up radiographs were obtained after odd-numbered treatment cycles in patients with open growth plates who did not experience disease progression prior to cycle 3. ResultsBaseline and follow-up growth plate radiographs were acquired in 48/53 (90%) of patients. Five patients (9.4%), all of whom received a specific VEGF/VEGFR blocking agent (sunitinib [n=1] or pazopanib [n=4]), had growth plate abnormalities. Four patients had growth plate widening that was apparent on at least two successive radiographs, but was not confirmed by MRI. The fifth patient had progressive growth plate widening and evidence of physeal cartilage hypertrophy on MRI. Subsequent off treatment radiographs showed that the growth plate changes were reversible. ConclusionGrowth plate abnormalities occur in a small, but relevant number of patients undergoing anti-angiogenic therapy. These results support the need for growth plate monitoring in children with open growth plates who are receiving anti-angiogenic therapy, and for improved methods to assess toxicity of anti-angiogenic agents to the developing skeleton. Pediatr Blood Cancer 2015;62:45-51. (c) 2014 Wiley Periodicals, Inc. C1 [Voss, Stephan D.] Boston Childrens Hosp, Dept Radiol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Glade-Bender, Julia] Columbia Univ, Med Ctr, Dept Pediat Oncol, New York, NY USA. [Spunt, Sheri L.] Stanford Univ, Dept Pediat Hematol Oncol, Lucile Packard Childrens Hosp, Palo Alto, CA 94304 USA. [DuBois, Steven G.] UCSF Med Ctr Parnassus, Dept Pediat Hematol Oncol, San Francisco, CA USA. [Widemann, Brigitte C.] NCI, Dept Pharmacol & Expt Therapeut, Pediat Oncol Branch, CCR,Mark O Hatfield Warren Grant Magnuson Clin Ct, Bethesda, MD 20892 USA. [Park, Julie R.; Leary, Sarah E. S.] Seattle Childrens Hosp, Dept Hematol Oncol, Seattle, WA USA. [Nelson, Marvin D.] Childrens Hosp Los Angeles, Dept Radiol, Los Angeles, CA 90027 USA. [Adamson, Peter C.] Childrens Hosp Philadelphia, Abramson Res Ctr, Philadelphia, PA 19104 USA. [Blaney, Susan M.] Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. [Weigel, Brenda] Univ Minnesota, Amplatz Childrens Hosp, Div Hematol & Oncol, Minneapolis, MN USA. RP Voss, SD (reprint author), Boston Childrens Hosp, Dept Radiol, Dana Farber Canc Inst, 300 Longwood Ave, Boston, MA 02115 USA. EM stephan.voss@childrens.harvard.edu OI Leary, Sarah/0000-0003-0225-6184 FU NCI NIH HHS [UM1 CA097452, 5UM1 CA097452-12] NR 39 TC 4 Z9 4 U1 0 U2 6 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 2015 VL 62 IS 1 BP 45 EP 51 DI 10.1002/pbc.25229 PG 7 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA AU0NG UT WOS:000345319300010 PM 25257751 ER PT J AU Trippett, TM Schwartz, CL Guillerman, RP Gamis, AS Gardner, S Hogan, S London, WB Chen, L de Alarcon, P AF Trippett, Tanya M. Schwartz, Cindy L. Guillerman, R. Paul Gamis, Alan S. Gardner, Sharon Hogan, Shirley London, Wendy B. Chen, Lu de Alarcon, Pedro TI Ifosfamide and Vinorelbine Is an Effective Reinduction Regimen in Children With Refractory/Relapsed Hodgkin Lymphoma, AHOD00P1: A Children's Oncology Group Report SO PEDIATRIC BLOOD & CANCER LA English DT Article DE hodgkin lymphoma; ifosfamide; re-induction; relapse; vinorelbine ID MALIGNANT SOLID TUMORS; GROUP PHASE-II; SALVAGE THERAPY; DISEASE; ETOPOSIDE; RECURRENT; CHEMOTHERAPY; CARBOPLATIN; TRANSPLANTATION; CHILDHOOD AB BackgroundWe assessed the safety and efficacy of ifosfamide and vinorelbine (IV) as a less toxic and effective reinduction regimen for pediatric patients with relapsed or refractory Hodgkin Lymphoma. ProcedureThis multi-center Children's Oncology Group phase II pilot study enrolled patients <30 years of age with biopsy-proven Hodgkin Lymphoma in relapse or refractory disease after front-line therapy. Treatment consisted of ifosfamide 3,000mg/m(2) intravenous infusion over 24 hr on Days 1-4 and vinorelbine 25mg/m(2)/dose intravenous push on Days 1 and 5 of each 21 day cycle with cytokine support. The study endpoints included estimation of key toxicities (cardiac, hepatic, or renal toxicity or toxic death), the rate of successful peripheral stem cell harvesting, and response after two cycles of therapy. ResultsSixty-six patients received a median of two cycles of IV. Sixty-four of 66 were heavily pretreated, 4 had refractory disease, 55% were male and 79% had nodular sclerosis HL. The primary toxicities were hematologic. Harvested peripheral stem cells were sufficient for autologous transplantation in 46 of 54 patients for whom stem cell collection was attempted. The overall response rate (72%; 95% CI 59-83%) permitted the majority of patients to undergo subsequent stem cell transplantation. ConclusionsIV is a safe and effective re-induction regimen for salvage of pediatric patients with relapsed or refractory Hodgkin Lymphoma with an excellent response rate and success of post chemotherapy stem cell harvest. It avoids the use of etoposide, an agent associated with secondary malignancy after stem cell transplantation. Pediatr Blood Cancer 2015;62:60-64. (c) 2014 Wiley Periodicals, Inc. C1 [Trippett, Tanya M.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Schwartz, Cindy L.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Guillerman, R. Paul] Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. [Gamis, Alan S.] Childrens Mercy Hosp & Clin, Kansas City, MO USA. [Gardner, Sharon] New York Univ Hosp, New York, NY USA. [Hogan, Shirley] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [London, Wendy B.] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA. [Chen, Lu] Stat & Data Ctr, Childrens Oncol Grp, Arcadia, CA USA. [de Alarcon, Pedro] Univ Illinois, Coll Med, Peoria, IL 61656 USA. RP Trippett, TM (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA. EM trippet1@mskcc.org RI Guillerman, Robert/R-1531-2016; OI Guillerman, Robert/0000-0001-8149-613X; gardner, sharon/0000-0002-8857-5487 FU NCI NIH HHS [U10 CA 180886, U10 CA-180899, U10 CA-98413, U10 CA029511, U10 CA098413, U10 CA098543, U10 CA180886, U10 CA180899, U10 CA98543] NR 26 TC 4 Z9 4 U1 0 U2 5 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 2015 VL 62 IS 1 BP 60 EP 64 DI 10.1002/pbc.25205 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA AU0NG UT WOS:000345319300012 PM 25308760 ER PT J AU Park, LG Howie-Esquivel, J Dracup, K AF Park, Linda G. Howie-Esquivel, Jill Dracup, Kathleen TI Electronic Measurement of Medication Adherence SO WESTERN JOURNAL OF NURSING RESEARCH LA English DT Article DE medication; medication adherence; measurement; electronic monitoring device ID DIABETES PATIENTS; DRUG ADHERENCE; THERAPY; DISEASE; DEVICE; TRIAL; INTERVENTIONS; PREVENTION; MANAGEMENT; CORONARY AB The measurement of medication adherence is important in both clinical practice and research settings to offer effective medical therapy, improve clinical outcomes, and determine the efficacy of therapy. The aims of this article are to (a) present an overview of current and developing electronic methods of medication measurement, (b) explore the advantages and disadvantages to each approach, and (c) discuss the implications of using electronic monitoring devices for clinical practice and research. A comprehensive review of electronic forms of medication measurement was performed. A description of each method is presented including oral medication monitors, personal electronic devices, electronic blisters, wirelessly observed therapy, inhaled medication monitors, mobile phones, video/photo-assisted observation, and electronic health records. Familiarity with using electronic devices and advances in technology will continue to develop and influence the measurement of medication adherence. C1 [Park, Linda G.] San Francisco VA Med Ctr, San Francisco, CA USA. [Park, Linda G.; Howie-Esquivel, Jill; Dracup, Kathleen] Univ Calif San Francisco, San Francisco, CA 94121 USA. RP Park, LG (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Div Geriatr, 4150 Clement St 181G, San Francisco, CA 94121 USA. EM linda.park@ucsf.edu RI Emchi, Karma/Q-1952-2016 NR 47 TC 4 Z9 4 U1 3 U2 14 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0193-9459 EI 1552-8456 J9 WESTERN J NURS RES JI West. J. Nurs. Res. PD JAN PY 2015 VL 37 IS 1 BP 28 EP 49 DI 10.1177/0193945914524492 PG 22 WC Nursing SC Nursing GA AU4NU UT WOS:000345589200003 PM 24577868 ER PT J AU Paintlia, MK Singh, I Singh, AK AF Paintlia, Manjeet K. Singh, Inderjit Singh, Avtar K. TI Effect of Vitamin D3 Intake on the Onset of Disease in a Murine Model of Human Krabbe Disease SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE Krabbe disease; twitcher mouse; demyelinating disease; oligodendrocyte; psychosine ID GLOBOID-CELL LEUKODYSTROPHY; BONE-MARROW-TRANSPLANTATION; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CENTRAL NERVOUS-SYSTEM; TANDEM MASS-SPECTROMETRY; TWITCHER MOUSE; MULTIPLE-SCLEROSIS; 1,25-DIHYDROXYVITAMIN D-3; GENE-THERAPY; OXIDATIVE STRESS AB Low vitamin D level is a risk factor for various late-onset CNS demyelinating disorders. We investigated whether vitamin D deficiency influences disease in twitcher mice (GALC(twi/twi); twi), a murine model of Krabbe disease (KD), an inherited disorder caused by galactocerebrosidase (GALC) deficiency that leads to psychosine accumulation, oligodendrocyte (OL) loss, and CNS demyelination. We found that the in situ 1,25-dihydroxyvitamin D3 level was reduced, with a parallel increase in the expression of inflammatory cytokines and vitamin D-catabolizing enzymes in the brains of KD and twi mice compared with age-matched controls. Pups maintained on milk from lactating heterozygous (GALC(twi/+)) mothers that were fed a vitamin D3-supplemented diet until weaning and then fed a vitamin D3-supplemented diet demonstrated delayed body weight loss and development of disease in twi mice. This delayed the onset of tremors and locomotor disabilities that eventually impacted the life span of twi mice (502 days). Accordingly, the expression of antioxidant enzymes was increased with delayed psychosine accumulation, lipid peroxidation, and inflammatory response that eventually protected CNS myelin and axonal integrity in twi mice. In vitro studies revealed that 1,25-dihydroxyvitamin D3 enhances antioxidant defenses in OLs deficient for GALC or incubated with psychosine. Together these data provide the first evidence that vitamin D deficiency affects disease development in twi mice and that vitamin D3 supplementation has the potential to improve the efficacy of KD therapeutics. (c) 2014 Wiley Periodicals, Inc. C1 [Paintlia, Manjeet K.; Singh, Inderjit; Singh, Avtar K.] Med Univ S Carolina, Dept Pediat, Darby Childrens Res Inst, Charleston, SC 29425 USA. [Singh, Avtar K.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Singh, Avtar K.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Singh, AK (reprint author), Med Univ S Carolina, Dept Pediat, 173 Ashley Ave, Charleston, SC 29425 USA. EM singhi@musc.edu FU National Institutes of Health [NS064195, NS072511] FX Contract grant sponsor: National Institutes of Health; Contract grant number: NS064195; Contract grant number: NS072511. NR 69 TC 4 Z9 4 U1 0 U2 7 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 2015 VL 93 IS 1 BP 28 EP 42 DI 10.1002/jnr.23476 PG 15 WC Neurosciences SC Neurosciences & Neurology GA AU0IR UT WOS:000345307200003 PM 25236689 ER PT J AU Martin, JT Collins, CM Ikuta, K Mauck, RL Elliott, DM Zhang, Y Anderson, DG Vaccaro, AR Albert, TJ Arlet, V Smith, HE AF Martin, John T. Collins, Christopher M. Ikuta, Kensuke Mauck, Robert L. Elliott, Dawn M. Zhang, Yeija Anderson, D. Greg Vaccaro, Alexander R. Albert, Todd J. Arlet, Vincent Smith, Harvey E. TI Population Average T2 MRI Maps Reveal Quantitative Regional Transformations in the Degenerating Rabbit Intervertebral Disc That Vary by Lumbar Level SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE intervertebral disc; degeneration; rabbit; MRI; T2 mapping ID LOW-BACK-PAIN; RELAXATION-TIMES; NEEDLE PUNCTURE; ANIMAL-MODEL; CARTILAGE; SPINE; INJURY; AGE; REPAIR; MOUSE AB Magnetic resonance imaging (MRI) with T2-weighting is routinely performed to assess intervertebral disc degeneration. Standard clinical evaluations of MR images are qualitative, however, and do not focus on region-specific alterations in the disc. Utilizing a rabbit needle puncture model, T2 mapping was performed on injured discs to develop a quantitative description of the degenerative process following puncture. To do so, an 18G needle was inserted into four discs per rabbit (L3/L4 to L6/L7) and T2 maps were generated pre- and 4 weeks post-injury. Individual T2 maps were normalized to a disc-specific coordinate system and then averaged for pre- and post-injury population composite T2 maps. We also developed a method to automatically segment the nucleus pulposus by fitting the NP region of the T2 maps with modified 2-D and 3-D Gaussian distribution functions. Puncture injury produced alterations in MR signal intensity in a region-specific manner mirroring human degeneration. Population average T2 maps provided a quantitative representation of the injury response, and identified deviations of individual degenerate discs from the pre-injury population. We found that the response to standardized injury was modest at lower lumbar levels, likely as a result of increased disc dimensions. These tools will be valuable for the quantitative characterization of disc degeneration in future clinical and pre-clinical studies. (c) 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:140-148, 2015. C1 [Martin, John T.; Ikuta, Kensuke; Mauck, Robert L.; Zhang, Yeija; Smith, Harvey E.] Philadelphia VA Med Ctr, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA. [Martin, John T.; Ikuta, Kensuke; Mauck, Robert L.; Zhang, Yeija; Arlet, Vincent; Smith, Harvey E.] Univ Penn, Dept Orthopaed Surg, Philadelphia, PA 19104 USA. [Martin, John T.; Mauck, Robert L.] Univ Penn, Dept Mech Engn & Appl Mech, Philadelphia, PA 19104 USA. [Collins, Christopher M.] NYU, Dept Radiol, New York, NY 10016 USA. [Mauck, Robert L.] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. [Elliott, Dawn M.] Univ Delaware, Dept Biomed Engn, Newark, DE USA. [Vaccaro, Alexander R.] Univ Penn, Dept Phys Med & Rehabil, Philadelphia, PA 19104 USA. [Anderson, D. Greg; Vaccaro, Alexander R.; Albert, Todd J.] Thomas Jefferson Univ, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. RP Smith, HE (reprint author), Philadelphia VA Med Ctr, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA. EM harvey.smith@uphs.upenn.edu FU NIAMS NIH HHS [P30 AR050950]; NIBIB NIH HHS [P41 EB017183, R01 EB000454]; NICHD NIH HHS [5K08HD049598, K08 HD049598]; RRD VA [IK2 RX001476] NR 49 TC 4 Z9 4 U1 7 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-0266 EI 1554-527X J9 J ORTHOP RES JI J. Orthop. Res. PD JAN PY 2015 VL 33 IS 1 BP 140 EP 148 DI 10.1002/jor.22737 PG 9 WC Orthopedics SC Orthopedics GA AU0WT UT WOS:000345343600019 PM 25273831 ER PT J AU Knipe, RS Tager, AM Liao, JK AF Knipe, Rachel S. Tager, Andrew M. Liao, James K. TI The Rho Kinases: Critical Mediators of Multiple Profibrotic Processes and Rational Targets for New Therapies for Pulmonary Fibrosis SO PHARMACOLOGICAL REVIEWS LA English DT Review ID GROWTH-FACTOR-BETA; EMBRYONIC STEM-CELLS; INDUCED LUNG INJURY; ANEURYSMAL SUBARACHNOID HEMORRHAGE; UNILATERAL URETERAL OBSTRUCTION; ENDOTHELIAL BARRIER DYSFUNCTION; ACTIVATES LATENT TGF-BETA-1; MUSCLE MYOSIN PHOSPHATASE; ROCK INHIBITOR Y-27632; PROTEIN-KINASE AB Idiopathic pulmonary fibrosis (IPF) is characterized by progressive lung scarring, short median survival, and limited therapeutic options, creating great need for new pharmacologic therapies. IPF is thought to result from repetitive environmental injury to the lung epithelium, in the context of aberrant host wound healing responses. Tissue responses to injury fundamentally involve reorganization of the actin cytoskeleton of participating cells, including epithelial cells, fibroblasts, endothelial cells, and macrophages. Actin filament assembly and actomyosin contraction are directed by the Rho-associated coiled-coil forming protein kinase (ROCK) family of serine/threonine kinases (ROCK1 and ROCK2). As would therefore be expected, lung ROCK activation has been demonstrated in humans with IPF and in animal models of this disease. ROCK inhibitors can prevent fibrosis in these models, and more importantly, induce the regression of already established fibrosis. Here we review ROCK structure and function, upstream activators and downstream targets of ROCKs in pulmonary fibrosis, contributions of ROCKs to profibrotic cellular responses to lung injury, ROCK inhibitors and their efficacy in animal models of pulmonary fibrosis, and potential toxicities of ROCK inhibitors in humans, as well as involvement of ROCKs in fibrosis in other organs. As we discuss, ROCK activation is required for multiple profibrotic responses, in the lung and multiple other organs, suggesting ROCK participation in fundamental pathways that contribute to the pathogenesis of a broad array of fibrotic diseases. Multiple lines of evidence therefore indicate that ROCK inhibition has great potential to be a powerful therapeutic tool in the treatment of fibrosis, both in the lung and beyond. C1 [Knipe, Rachel S.; Tager, Andrew M.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Knipe, Rachel S.; Tager, Andrew M.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Knipe, Rachel S.; Tager, Andrew M.] Harvard Univ, Sch Med, Boston, MA USA. [Liao, James K.] Univ Chicago, Dept Med, Cardiol Sect, Chicago, IL 60637 USA. RP Liao, JK (reprint author), Univ Chicago, Dept Med, Cardiol Sect, 5841 S Maryland Ave MC 6080, Chicago, IL 60637 USA. EM jliao@medicine.bsd.uchicago.edu FU National Institutes of Health National Heart, Lung, and Blood Institute [T32-HL116275, R01-HL095732, R01-HL108975, R01-HL052233, R01-HL091933]; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [R01-DK085006]; National Institutes of Health National Institute of Neurological Disorders and Stroke [R01-NS070001]; Nirenberg Center for Advanced Lung Disease; Scleroderma Research Foundation FX This research was supported by the National Institutes of Health National Heart, Lung, and Blood Institute [Grants T32-HL116275 (to R.S.K.), R01-HL095732 and R01-HL108975 (to A.M.T.), and R01-HL052233 and R01-HL091933 (to J.K.L.)]; the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grant R01-DK085006 (to J.K.L.)]; the National Institutes of Health National Institute of Neurological Disorders and Stroke [Grant R01-NS070001 (to J.K.L.)]; and the Nirenberg Center for Advanced Lung Disease and the Scleroderma Research Foundation [(to A.M.T.)]. NR 148 TC 20 Z9 22 U1 2 U2 31 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0031-6997 EI 1521-0081 J9 PHARMACOL REV JI Pharmacol. Rev. PD JAN PY 2015 VL 67 IS 1 BP 103 EP 117 DI 10.1124/pr.114.009381 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AT7LW UT WOS:000345119500004 PM 25395505 ER PT J AU Liu, Y Sun, ZS Sun, SF Duan, YX Shi, JF Qi, ZF Meng, R Sun, YX Zeng, XW Chui, DH Ji, XM AF Liu, Yi Sun, Zhishan Sun, Shufeng Duan, Yunxia Shi, Jingfei Qi, Zhifeng Meng, Ran Sun, Yongxin Zeng, Xianwei Chui, Dehua Ji, Xunming TI Effects of Hypoxic Preconditioning on Synaptic Ultrastructure in Mice SO SYNAPSE LA English DT Article DE hypoxic preconditioning; synaptic curvature; presynaptic mitochondria ID LONG-TERM POTENTIATION; CEREBRAL-ISCHEMIA; DENTATE GYRUS; PLASTICITY; MORPHOLOGY; SYNAPSES; INJURY AB Hypoxic preconditioning (HPC) elicits resistance to more drastic subsequent insults, which potentially provide neuroprotective therapeutic strategy, but the underlying mechanisms remain to be fully elucidated. Here, we examined the effects of HPC on synaptic ultrastructure in olfactory bulb of mice. Mice underwent up to five cycles of repeated HPC treatments, and hypoxic tolerance was assessed with a standard gasp reflex assay. As expected, HPC induced an increase in tolerance time. To assess synaptic responses, Western blots were used to quantify protein levels of representative markers for glia, neuron, and synapse, and transmission electron microscopy was used to examine synaptic ultrastructure and mitochondrial density. HPC did not significantly alter the protein levels of astroglial marker (GFAP), neuron-specific markers (GAP43, Tuj-1, and OMP), synaptic number markers (synaptophysin and SNAP25) or the percentage of excitatory synapses versus inhibitory synapses. However, HPC significantly affected synaptic curvature and the percentage of synapses with presynaptic mitochondria, which showed concomitant change pattern. These findings demonstrate that HPC is associated with changes in synaptic ultrastructure. (C) 2014 Wiley Periodicals, Inc. C1 [Liu, Yi; Sun, Zhishan; Duan, Yunxia; Shi, Jingfei; Qi, Zhifeng; Meng, Ran; Sun, Yongxin; Ji, Xunming] Capital Med Univ, Xuanwu Hosp, CAJIN, Beijing 100053, Peoples R China. [Liu, Yi] Harvard Univ, Sch Med, Dept Radiol, Neuroprotect Res Lab,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Liu, Yi] Harvard Univ, Sch Med, Dept Neurol, Neuroprotect Res Lab,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Sun, Zhishan; Zeng, Xianwei] Weifang Med Coll, Affiliated Hosp, Dept Neurosurg, Weifang, Peoples R China. [Sun, Shufeng] Chinese Acad Sci, Inst Biophys, Ctr Biol Electron Microscopy, Beijing 100101, Peoples R China. [Chui, Dehua] Peking Univ, Hlth Sci Ctr, Neurosci Res Inst, Beijing 100191, Peoples R China. [Chui, Dehua] Peking Univ, Hlth Sci Ctr, Minist Publ Hlth, Dept Neurobiol,Key Lab Neurosci,Minist Educ, Beijing 100191, Peoples R China. RP Ji, XM (reprint author), Capital Med Univ, Xuanwu Hosp, 45 Changchun St, Beijing 100053, Peoples R China. EM jixm@ccmu.edu.cn FU National Natural Science Foundation of China [81200915] FX Contract grant sponsor: National Natural Science Foundation of China; Contract grant number: 81200915. NR 20 TC 2 Z9 2 U1 0 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0887-4476 EI 1098-2396 J9 SYNAPSE JI Synapse PD JAN PY 2015 VL 69 IS 1 BP 7 EP 14 DI 10.1002/syn.21777 PG 8 WC Neurosciences SC Neurosciences & Neurology GA AT9UG UT WOS:000345271100002 PM 25155519 ER PT J AU Businelle, MS Poonawalla, IB Kendzor, DE Rios, DM Cuate, EL Savoy, EJ Ma, P Baggett, TP Reingle, J Reitzel, LR AF Businelle, Michael S. Poonawalla, Insiya B. Kendzor, Darla E. Rios, Debra M. Cuate, Erica L. Savoy, Elaine J. Ma, Ping Baggett, Travis P. Reingle, Jennifer Reitzel, Lorraine R. TI Smoking policy change at a homeless shelter: Attitudes and effects SO ADDICTIVE BEHAVIORS LA English DT Article DE Homelessness; Tobacco; Smoking ban; Policy ID CIGARETTE-SMOKING; ADULTS; CESSATION; MORTALITY; EMPLOYEE; IMPACT AB Homeless adults are exposed to more smokers and smoke in response to environmental tobacco cues more than other socioeconomically disadvantaged groups. Addressing the culture of smoking in homeless shelters through policy initiatives may support cessation and improve health in this vulnerable and understudied population. This study examined support for and expected/actual effects of a smoking ban at a homeless shelter. A 2-wave cross-sectional study with an embedded cohort was conducted in the summer of 2013 two weeks before (wave 1) and two months after (wave 2) a partial outdoor smoking ban was implemented. A total of 394 homeless adults were surveyed (i.e., wave 1 [n = 155]; wave 2 [n = 150]; and 89 additional participants completed both waves). On average, participants were 43 years old, primarily African American (63%), male (72%), and had been homeless for the previous 12 months (median). Most participants were smokers (76%) smoking 12 cigarettes per day on average. Most participants supported the creation of a large smoke-free zone on the shelter campus, but there was less support for a shelter-wide smoking ban. Average cigarettes smoked per day did not differ between study waves. However, participants who completed both study waves experienced a reduction in expired carbon monoxide at wave 2 (W1 = 18.2 vs. W2 = 15.8 parts per million, p =.02). Expected effects of the partial ban were similar to actual effects. Partial outdoor smoking bans may be well supported by homeless shelter residents and may have a positive impact on shelter resident health. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Businelle, Michael S.; Poonawalla, Insiya B.; Kendzor, Darla E.; Rios, Debra M.; Cuate, Erica L.; Ma, Ping; Reingle, Jennifer] Univ Texas Dallas, Sch Publ Hlth, Dept Hlth Promot & Behav Sci, Dallas, TX 75390 USA. [Businelle, Michael S.; Kendzor, Darla E.; Ma, Ping] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Savoy, Elaine J.] Univ Houston, Dept Clin Psychol, Houston, TX USA. [Baggett, Travis P.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Reitzel, Lorraine R.] Univ Houston, Dept Educ Psychol, Houston, TX USA. RP Businelle, MS (reprint author), Univ Texas Dallas, Sch Publ Hlth, 6011 Harry Hines Blvd,V8-112, Dallas, TX 75390 USA. EM michael.businelle@utsouthwestern.edu OI Kendzor, Darla/0000-0002-7273-1916; Businelle, Michael/0000-0002-9038-2238 FU University of Texas Health Science Center, School of Public Health; University of Texas MD Anderson Cancer Center; American Cancer Society [MRSGT-10-104-01-CPHPS, MRSGT-12-114-01-CPPB] FX This work was supported by institutional funding provided by the University of Texas Health Science Center, School of Public Health (to MSB) and the University of Texas MD Anderson Cancer Center (to LRR). Data analysis and manuscript preparation were additionally supported through grant MRSGT-10-104-01-CPHPS (to Kendzor) and MRSGT-12-114-01-CPPB (to Businelle) awarded by the American Cancer Society. The funding sources had no further role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 24 TC 7 Z9 7 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 EI 1873-6327 J9 ADDICT BEHAV JI Addict. Behav. PD JAN PY 2015 VL 40 BP 51 EP 56 DI 10.1016/j.addbeh.2014.08.013 PG 6 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA AT3GO UT WOS:000344824100009 PM 25222848 ER PT B AU Rapoza, PA AF Rapoza, Peter A. BE Henderson, BA Yoo, SH TI WHAT CAUSES A Z-SYNDROME? HOW DO YOU DIAGNOSE AND MANAGE IT? SO CURBSIDE CONSULTATION IN REFRACTIVE AND LENS-BASED SURGERY LA English DT Article; Book Chapter C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02138 USA. RP Rapoza, PA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02138 USA. NR 4 TC 0 Z9 0 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-083-2 PY 2015 BP 195 EP 198 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BB5DE UT WOS:000343683200048 ER PT J AU Gifford, KA Liu, DD Carmona, H Lu, ZQ Romano, R Tripodis, Y Martin, B Kowall, N Jefferson, AL AF Gifford, Katherine A. Liu, Dandan Carmona, Hugo Lu, Zengqi Romano, Raymond Tripodis, Yorghos Martin, Brett Kowall, Neil Jefferson, Angela L. TI Inclusion of an Informant Yields Strong Associations between Cognitive Complaint and Longitudinal Cognitive Outcomes in Non-Demented Elders SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Mild cognitive impairment; cognitive complaint; dementia; cognition; Alzheimer's disease ID SUBJECTIVE MEMORY IMPAIRMENT; UNIFORM DATA SET; PRECLINICAL ALZHEIMERS-DISEASE; OLDER-ADULTS; AMNESTIC MCI; DEMENTIA; DECLINE; PREDICTION; INDIVIDUALS; DIAGNOSIS AB Background: The relation between the source of cognitive complaint and objective cognitive performance is not well understood. Objective: Examine self and informant cognitive complaint as predictors of objective cognitive and functional trajectory in non-demented elders. Methods: Participants from the National Alzheimer's Coordinating Center had a baseline diagnosis of normal cognition (NC; n = 6133, 72 +/- 8 years, 68% female) or mild cognitive impairment (MCI; n = 3010, 74 +/- 8 years, 55% female). Four independent groups defined cognitive complaint: no complaint, self-only complaint, informant-only complaint, or mutual complaint (both self and informant complaint). Linear mixed model regression analyses related complaint status (referent was no complaint) to cognitive and functional trajectories, adjusting for age, sex, race, education, and follow-up period. Results: Among NC participants, mutual complaint related to faster decline in global cognition (p < 0.0001), language (all p-values < 0.0001), processing speed (p = 0.0002), and executive functioning (p = 0.0006). Informant-only complaint related to faster decline in global cognition (p = 0.0001) and processing speed (p = 0.0001). Self-only complaint related to greater decline in immediate (p < 0.0001) and delayed (p = 0.0005) episodic memory. In MCI, mutual complaint related to faster decline in global cognition (p < 0.0001), verbal episodic memory (all p-values <0.0001), language (all p-values <0.0001), and processing speed (all p-values <0.0006). Informant-only or self-only complaint associations with cognitive trajectory did not survive correction factor for multiple comparisons. Conclusion: Cognitive complaint appears to have clinical significance, as it is related to declines in objective cognitive performance over time. Mutual complaint was associated with the worst cognitive trajectory in both NC and MCI elders, highlighting the importance of incorporating an informant into evaluation of elders whenever feasible. C1 [Gifford, Katherine A.; Romano, Raymond; Jefferson, Angela L.] Vanderbilt Univ, Med Ctr, Dept Neurol, Vanderbilt Memory & Alzheimers Ctr, Nashville, TN 37203 USA. [Liu, Dandan; Lu, Zengqi] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37203 USA. [Carmona, Hugo] Boston Univ, Sch Med, Boston, MA 02118 USA. [Tripodis, Yorghos; Martin, Brett; Kowall, Neil] Boston Univ, Sch Med, Alzheimers Dis Ctr, Boston, MA 02118 USA. [Tripodis, Yorghos] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Martin, Brett] Data Coordinating Ctr, Boston, MA USA. [Kowall, Neil] VA Boston Healthcare Syst, Boston, MA USA. RP Jefferson, AL (reprint author), Vanderbilt Univ, Med Ctr, Dept Neurol, 2525 West End Ave,12th,Floor,Suite 1200, Nashville, TN 37203 USA. EM angela.jefferson@vanderbilt.edu RI Kowall, Neil/G-6364-2012; OI Kowall, Neil/0000-0002-6624-0213; Tripodis, Yorghos/0000-0003-2190-7608 FU National Alzheimer's Coordinating Center [U01-AG016976]; Alzheimer's Association [NIRG-13-283276, IIRG-08-88733]; NACC Junior Investigator Award [2011-JI-08]; Paul B. Beeson Career Development Award in Aging [K23-AG030962]; Boston University Alzheimer's Disease Core Center [P30-AG013846]; General Clinical Research Centers Program of the National Center for Research Resources, NIH [M01-RR00533]; [T32-AG036697]; [K24-AG046373]; [R01-AG034962] FX U01-AG016976 (National Alzheimer's Coordinating Center); Alzheimer's Association NIRG-13-283276 (KAG); NACC Junior Investigator Award #2011-JI-08 (KAG); T32-AG036697 (KAG); K23-AG030962 (Paul B. Beeson Career Development Award in Aging; ALJ); K24-AG046373 (ALJ); Alzheimer's Association IIRG-08-88733 (ALJ); R01-AG034962 (ALJ); P30-AG013846 (Boston University Alzheimer's Disease Core Center); M01-RR00533 (General Clinical Research Centers Program of the National Center for Research Resources, NIH) NR 46 TC 9 Z9 9 U1 3 U2 10 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 2015 VL 43 IS 1 BP 121 EP 132 DI 10.3233/JAD-131925 PG 12 WC Neurosciences SC Neurosciences & Neurology GA AS8WM UT WOS:000344525900012 PM 25061054 ER PT J AU Radwan, FFY Hossain, A God, JM Leaphart, N Elvington, M Nagarkatti, M Tomlinson, S Haque, A AF Radwan, Faisal F. Y. Hossain, Azim God, Jason M. Leaphart, Nathan Elvington, Michelle Nagarkatti, Mitzi Tomlinson, Stephen Haque, Azizul TI Reduction of Myeloid-Derived Suppressor Cells and Lymphoma Growth by a Natural Triterpenoid SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE TRITERPENOID; LYMPHOMA; MITOCHONDRIA; CASPASES; APOPTOSIS; T CELLS; HLA CLASS II PROTEINS; MYELOID-DERIVED SUPPRESSOR CELLS; STAT3 ID II ANTIGEN PRESENTATION; BREAST-CANCER CELLS; LYSOSOMAL THIOL REDUCTASE; BH3-ONLY PROTEIN BIM; GANODERMA-LUCIDUM; ANTITUMOR IMMUNITY; SIGNALING PATHWAY; RECOGNITION; APOPTOSIS; ACID AB Lymphoma is a potentially life threatening disease. The goal of this study was to investigate the therapeutic potential of a natural triterpenoid, Ganoderic acid A (GA-A) in controlling lymphoma growth both in vitro and in vivo. Here, we show that GA-A treatment induces caspase-dependent apoptotic cell death characterized by a dose-dependent increase in active caspases 9 and 3, up-regulation of pro-apoptotic BIM and BAX proteins, and a subsequent loss of mitochondrial membrane potential with release of cytochrome c. In addition to GA-A's anti-growth activity, we show that lower doses of GA-A enhance HLA class II-mediated antigen (Ag) presentation and CD4+ T cell recognition of lymphoma cells in vitro. The therapeutic relevance of GA-A treatment was also tested in vivo using the EL4 syngeneic mouse model of metastatic lymphoma. GA-A-treatment significantly prolonged survival of EL4 challenged mice and decreased tumor metastasis to the liver, an outcome accompanied by a marked down-regulation of STAT3 phosphorylation, reduction myeloid-derived suppressor cells (MDSCs), and enhancement of cytotoxic CD8+ T cells in the host. Thus, GA-A not only selectively induces apoptosis in lymphoma cells, but also enhances cell-mediated immune responses by attenuating MDSCs, and elevating Ag presentation and T cell recognition. The demonstrated therapeutic benefit indicates that GA-A is a candidate for future drug design for the treatment of lymphoma. J. Cell. Biochem. 116: 102-114, 2015. (c) 2014 Wiley Periodicals, Inc. C1 [Radwan, Faisal F. Y.; Hossain, Azim; God, Jason M.; Leaphart, Nathan; Elvington, Michelle; Tomlinson, Stephen; Haque, Azizul] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Radwan, Faisal F. Y.; Hossain, Azim; God, Jason M.; Leaphart, Nathan; Elvington, Michelle; Tomlinson, Stephen; Haque, Azizul] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. [Radwan, Faisal F. Y.; Hossain, Azim; God, Jason M.; Leaphart, Nathan; Elvington, Michelle; Tomlinson, Stephen; Haque, Azizul] Med Univ S Carolina, Childrens Res Inst, Charleston, SC 29425 USA. [Nagarkatti, Mitzi] Univ S Carolina, Sch Med, Dept Pathol Microbiol & Immunol, Columbia, SC 29208 USA. [Tomlinson, Stephen] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Haque, A (reprint author), Med Univ S Carolina, Dept Microbiol & Immunol, 173 Ashley Ave,BS 208, Charleston, SC 29425 USA. EM haque@musc.edu OI Nagarkatti, Mitzi/0000-0002-5977-5615 FU National Institutes of Health [R01 CA129560, R01 CA129560-S1, R01 CA158179]; Cancer Center Support Grant [P30 CA138313] FX Grant sponsor: National Institutes of Health; Grant numbers: R01 CA129560, R01 CA129560-S1, R01 CA158179; Grant sponsor: Cancer Center Support Grant; Grant number: P30 CA138313. NR 59 TC 7 Z9 8 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0730-2312 EI 1097-4644 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN PY 2015 VL 116 IS 1 BP 102 EP 114 DI 10.1002/jcb.24946 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AT2YB UT WOS:000344799200011 PM 25142864 ER PT J AU Zetumer, S Young, I Shear, MK Skritskaya, N Lebowitz, B Simon, N Reynolds, C Mauro, C Zisook, S AF Zetumer, Samuel Young, Ilanit Shear, M. Katherine Skritskaya, Natalia Lebowitz, Barry Simon, Naomi Reynolds, Charles Mauro, Christine Zisook, Sidney TI The impact of losing a child on the clinical presentation of complicated grief SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Complicated grief; Prolonged grief; Persistent complex bereavement disorder; Child loss; Bereavement; Grief ID GLOBAL IMPRESSION SCALE; TRAUMATIC GRIEF; EMPIRICAL-TEST; VIOLENT DEATH; BEREAVEMENT; DEPRESSION; PARENTS; SUICIDALITY; VALIDATION; PREDICTORS AB Background: It is unclear whether bereaved parents with Complicated Grief (CG) struggle with their grief differently than others with CG. This study addressed this question by comparing CG severity, CC-related symptoms, thoughts and behaviors, and comorbid psychiatric diagnoses of bereaved parents with CG to the diagnoses and symptoms of others with CG. Methods: Baseline data from 345 participants enrolled in the Healing Emotions After Loss (HEAL) study, a multi-site CG treatment study, were used to compare parents with CG (n=75) to others with CG (n=275). Data from the parent group was then used to compare parents with CG who had lost a younger child (n=24) to parents with CG who had lost an older child (n=34). Demographic and loss-related data were also gathered and used to control for confounders between groups. Results: Parents with CG demonstrated slightly higher levels of CG (p=0.025), caregiver self-blame (p=0.007), and suicidality (p=0.025) than non-parents with CG. Parents who had lost younger children were more likely to have had a wish to be dead since the loss than parents who had lost older children (p=0.041). Limitations: All data were gathered from a treatment research study, limiting the generalizability of these results. No corrections were made for multiple comparisons. The comparison of parents who lost younger children to parents who lost older children was limited by a small sample size. Conclusions: Even in the context of CG, the relationship to the deceased may have a bearing on the degree and severity of grief symptoms and associated features. Bereaved parents with CG reported more intense CG, self-blame, and suicidality than other bereaved groups with CG, though this finding requires confirmation. The heightened levels of suicidal ideation experienced by parents with CG, especially after losing a younger child, suggest the value of routinely screening for suicidal thoughts and behaviors in this group. Published by Elsevier B.V. C1 [Zetumer, Samuel; Young, Ilanit; Lebowitz, Barry; Zisook, Sidney] Vet Affairs San Diego Healthcare Syst, La Jolla, CA USA. [Zetumer, Samuel; Young, Ilanit; Lebowitz, Barry; Zisook, Sidney] Vet Med & Res Fdn, La Jolla, CA USA. [Young, Ilanit; Zisook, Sidney] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92161 USA. [Shear, M. Katherine; Lebowitz, Barry] Columbia Univ, Sch Social Work, Complicated Grief Treatment Res Program, New York, NY 10027 USA. [Shear, M. Katherine] Univ Coll Phys & Surg, New York, NY USA. [Skritskaya, Natalia] Columbia Univ, Dept Biostat & Psychiat, New York, NY USA. [Simon, Naomi] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. [Simon, Naomi] Massachusetts Gen Hosp, Complicated Grief Program, Boston, MA 02114 USA. [Reynolds, Charles] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Reynolds, Charles] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Community & Behav Hlth Sci, Western Psychiat Inst & Clin, Pittsburgh, PA USA. RP Zisook, S (reprint author), Univ Calif San Diego, Dept Psychiat, 3350 La Jolla Village Dr, La Jolla, CA 92161 USA. EM szisook@ucsd.edu FU National Institute of Mental Health [NIMH R01 MH085207]; American Foundation for Suicide Prevention; John Majda Foundation FX Funding for the HEAL study was provided by the National Institute of Mental Health (NIMH R01 MH085207), the American Foundation for Suicide Prevention, and the John Majda Foundation. They had no further role in this manuscript's study design, in the analysis and interpretation of data, in the writing of the report, or in the decision to submit the paper. NR 45 TC 9 Z9 9 U1 2 U2 23 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 1 PY 2015 VL 170 BP 15 EP 21 DI 10.1016/j.jad.2014.08.021 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AS4ET UT WOS:000344226700003 PM 25217759 ER PT J AU Bui, E Horenstein, A Shah, R Skritskaya, NA Mauro, C Wang, YJ Duan, N Reynolds, CF Zisook, S Shear, MK Simon, NM AF Bui, Eric Horenstein, Arielle Shah, Riva Skritskaya, Natalia A. Mauro, Christine Wang, Yuanjia Duan, Naihua Reynolds, Charles F., III Zisook, Sidney Shear, M. Katherine Simon, Naomi M. TI Grief-related panic symptoms in Complicated Grief SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Grief; Bereavement; Grief-Related Panic; Panic Disorder; Functional Impairment ID EXPERIENTIAL AVOIDANCE; ANXIETY SENSITIVITY; IMPAIRMENT; SCALE; PREVALENCE; DISORDER; ATTACKS AB Background: Although Complicated Grief (CG) has been associated with comorbid Panic Disorder (PD), little is known about panic attacks in CG, and whether panic symptoms may be grief-related. The present study examines the presence and impact of grief-related panic symptoms in CG. Methods: Individuals with CG (n=146, 78% women, mean (SD) age=52.4(15.0)) were assessed for CG, DSM-IV diagnoses, work and social impairment, and with the Panic Disorder Severity Scale modified to assess symptoms "related to or triggered by reminders of your loss" and anticipatory worry. Results: Overall, 39.7% reported at least one full or limited-symptom grief-related panic attack over the past week, and 32.2% reported some level of anticipatory worry about grief-related panic. Of interest, 17% met DSM criteria for PD. Among those without PD, 34.7% reported at least one full or limited-symptom grief-related panic attack over the past week, and this was associated with higher CG symptom severity (t = -2.23, p < 0.05), and functional impairment (t = -3.31, p < 0.01). Among the full sample, controlling for CG symptom severity and current PD, the presence of at least one full or limited-symptom grief-related panic attack was independently associated with increased functional impairment (B(SE)=4.86(1.7), p < 0.01). Limitations: Limitations include a lack of assessment of non-grief-related panic symptoms and examination of a sample of individuals seeking treatment for CG. Conclusions: Grief-related panic symptoms may be prevalent among individuals with CG and independently contribute to distress and functional impairment. (C) 2014 Elsevier RV. All rights reserved. C1 [Bui, Eric; Horenstein, Arielle; Shah, Riva; Simon, Naomi M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Bui, Eric; Simon, Naomi M.] Harvard Univ, Sch Med, Boston, MA USA. [Skritskaya, Natalia A.; Shear, M. Katherine] Columbia Sch Social Work, New York, NY USA. [Mauro, Christine; Wang, Yuanjia] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA. [Duan, Naihua] Columbia Univ, Dept Psychiat, Div Biostat, New York, NY USA. [Reynolds, Charles F., III] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Zisook, Sidney] Univ Calif San Diego, San Diego, CA 92103 USA. [Zisook, Sidney] VA San Diego Healthcare Syst, San Diego, CA USA. [Shear, M. Katherine] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. RP Bui, E (reprint author), Massachusetts Gen Hosp, One Bowdoin Sq,Suite 650, Boston, MA 02114 USA. EM tebui@mgh.harvard.edu RI Bui, Eric/J-8347-2015 OI Bui, Eric/0000-0002-1413-6473 FU National Institute of Health, United States [P30 MH90333, R01 MH085288, R01 MH060783, R01 MH085308, R01 MH085297] FX This study was supported by Grants P30 MH90333, R01 MH085288, R01 MH060783, R01 MH085308, and R01 MH085297, from the National Institute of Health, United States. The funding source had no role in study design; data collection, analysis, or interpretation; or in writing of the manuscript and submission process. NR 18 TC 1 Z9 1 U1 3 U2 15 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 1 PY 2015 VL 170 BP 213 EP 216 DI 10.1016/j.jad.2014.08.028 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AS4ET UT WOS:000344226700033 PM 25254619 ER PT S AU Nishida, A Lau, CW Mizoguchi, A AF Nishida, Atsushi Lau, Cindy W. Mizoguchi, Atsushi BE Stowell, SR Cummings, RD TI Examination of the Role of Galectins in Intestinal Inflammation SO GALECTINS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Colitis; Epithelial cell isolation; Galectins; Inflammatory Bowel Disease; Lamina propria cell isolation; Mouse models ID DEXTRAN SULFATE SODIUM; CD4(+) T-CELLS; BOWEL-DISEASE; EXPERIMENTAL COLITIS; ULCERATIVE-COLITIS; MICE; MODELS; PATHOGENESIS; LYMPHOCYTES; TEMPERATURE AB The intestine, which provides the first line of defense against over trillion of enteric microorganisms, suffers from broad range of inflammatory conditions caused by infectious, autoimmune, allergic, neurological, and ischemic mechanisms. Recent data have suggested dual roles (protective versus deleterious) for galectins in the pathogenesis of some intestinal inflammations, highlighting the importance of this area of research. A potential problem with the research of intestinal inflammation may be the requirement of some unique techniques. Therefore, we herein describe how to induce intestinal inflammation and how to isolate lymphocyte, myeloid cell, follicular cell, and epithelial cell populations separately from the intestine for the study of intestinal inflammations. C1 [Nishida, Atsushi] Massachusetts Gen Hosp, Mol Pathol Unit, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Nishida, Atsushi] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Lau, Cindy W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Pathol Unit, Boston, MA USA. [Lau, Cindy W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA USA. [Mizoguchi, Atsushi] Kurume Univ, Sch Med, Dept Immunol, Kurume, Fukuoka 830, Japan. RP Nishida, A (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. FU NIAID NIH HHS [R01AI081807]; NIDDK NIH HHS [R01DK091247, R01DK064351] NR 33 TC 1 Z9 1 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1396-1; 978-1-4939-1395-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1207 BP 231 EP 248 DI 10.1007/978-1-4939-1396-1_15 D2 10.1007/978-1-4939-1396-1 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BB4NH UT WOS:000343241200016 PM 25253144 ER PT S AU Ribeiro, SM Gimenez-Cassina, A Danial, NN AF Ribeiro, Sofia M. Gimenez-Cassina, Alfredo Danial, Nika N. BE Palmeira, CM Rolo, AP TI Measurement of Mitochondrial Oxygen Consumption Rates in Mouse Primary Neurons and Astrocytes SO MITOCHONDRIAL REGULATION: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Oxygen consumption rate; Neurons; Astrocytes; Bioenergetics; Extracellular flux ID BIOENERGETICS; DYSFUNCTION AB The introduction of microplate-based assays that measure extracellular fluxes in intact, living cells has revolutionized the field of cellular bioenergetics. Here, we describe a method for real time assessment of mitochondrial oxygen consumption rates in primary mouse cortical neurons and astrocytes. This method requires the Extracellular Flux Analyzer Instrument (XF24, Seahorse Biosciences), which uses fluorescent oxygen sensors in a microplate assay format. C1 [Ribeiro, Sofia M.; Gimenez-Cassina, Alfredo; Danial, Nika N.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Ribeiro, Sofia M.] Univ Coimbra, PhD Programme Expt Biol & Biomed PDBEB, CNC Ctr Neurosci & Cell Biol, Coimbra, Portugal. [Ribeiro, Sofia M.] Inst Interdisciplinary Res IIIUC, Coimbra, Portugal. [Gimenez-Cassina, Alfredo; Danial, Nika N.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. RP Ribeiro, SM (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. OI Gimenez-Cassina, Alfredo/0000-0002-2768-2350 FU NINDS NIH HHS [R56 NS072142] NR 12 TC 5 Z9 5 U1 0 U2 9 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-1875-1; 978-1-4939-1874-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1241 BP 59 EP 69 DI 10.1007/978-1-4939-1875-1_6 D2 10.1007/978-1-4939-1875-1 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BB4SR UT WOS:000343314000007 PM 25308488 ER PT J AU Manchikanti, L Hirsch, JA AF Manchikanti, Laxmaiah Hirsch, Joshua A. TI Comment on the Paper Entitled 'Haemostasis and Safety Measures before Lumbar Puncture at the Haematology Ward: The Danish Routines' SO ACTA HAEMATOLOGICA LA English DT Editorial Material ID RISK C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY 42003 USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Endovasc Neurosurg & Neuroendovasc Program, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Manchikanti, L (reprint author), Pain Management Ctr Paducah, 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 6 TC 0 Z9 0 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5792 EI 1421-9662 J9 ACTA HAEMATOL-BASEL JI Acta Haematol. PY 2015 VL 133 IS 1 BP 106 EP 107 DI 10.1159/000363563 PG 2 WC Hematology SC Hematology GA AQ4CJ UT WOS:000342739500021 PM 25248051 ER PT B AU Boulter, DJ Mukundan, G Schaefer, PW AF Boulter, Daniel J. Mukundan, Govind Schaefer, Pamela W. BE Stein, J Harvey, RL Winstein, CJ Zorowitz, RD Wittenberg, GF TI Neuroimaging of Acute Stroke SO STROKE RECOVERY AND REHABILITATION, SECOND EDITION LA English DT Article; Book Chapter ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN-ACTIVATOR; MIDDLE CEREBRAL-ARTERY; DIFFUSION-WEIGHTED MR; BRAIN-BARRIER PERMEABILITY; ANGIOGRAPHY SOURCE IMAGES; ACUTE HEMISPHERIC STROKE; POSITRON-EMISSION-TOMOGRAPHY; PERFUSION CT ASSESSMENT; HEMORRHAGIC TRANSFORMATION C1 [Boulter, Daniel J.; Schaefer, Pamela W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02163 USA. [Mukundan, Govind] Sutter Med Grp, Sutter Imaging, Neuroradiol Sect, Sacramento, CA USA. RP Boulter, DJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02163 USA. NR 120 TC 0 Z9 0 U1 0 U2 3 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-006-8 PY 2015 BP 56 EP 81 PG 26 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BB2VG UT WOS:000342391500004 ER PT B AU Greenberg, SM Reijmer, YD AF Greenberg, Steven M. Reijmer, Yael D. BE Stein, J Harvey, RL Winstein, CJ Zorowitz, RD Wittenberg, GF TI Memory, Executive Function, and Dementia SO STROKE RECOVERY AND REHABILITATION, SECOND EDITION LA English DT Article; Book Chapter ID VASCULAR COGNITIVE IMPAIRMENT; ASSOCIATION/AMERICAN STROKE ASSOCIATION; APOLIPOPROTEIN-E EPSILON-4; WHITE-MATTER LESIONS; MINI-MENTAL-STATE; ALZHEIMERS-DISEASE; ISCHEMIC-STROKE; BLOOD-PRESSURE; POSTSTROKE DEMENTIA; RISK-FACTORS C1 [Greenberg, Steven M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hemorrhag Stroke Res Program, Boston, MA 02163 USA. [Reijmer, Yael D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Stroke Res, Boston, MA USA. RP Greenberg, SM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hemorrhag Stroke Res Program, Boston, MA 02163 USA. NR 117 TC 0 Z9 0 U1 0 U2 2 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-006-8 PY 2015 BP 241 EP 248 PG 8 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BB2VG UT WOS:000342391500016 ER PT B AU Mulroy, SJ Kautz, SA Sullivan, KJ AF Mulroy, Sara J. Kautz, Steven A. Sullivan, Katherine J. BE Stein, J Harvey, RL Winstein, CJ Zorowitz, RD Wittenberg, GF TI Walking Recovery and Rehabilitation After Stroke SO STROKE RECOVERY AND REHABILITATION, SECOND EDITION LA English DT Article; Book Chapter ID RANDOMIZED CONTROLLED-TRIAL; FUNCTIONAL ELECTRICAL-STIMULATION; WEIGHT-SUPPORTED TREADMILL; CORTICOSPINAL TRACT INTEGRITY; ABNORMAL SYNERGY PATTERNS; PERONEAL NERVE STIMULATOR; IMPROVES MUSCLE STRENGTH; GROUND REACTION FORCES; GAIT FOLLOWING STROKE; POSTSTROKE HEMIPARESIS C1 [Mulroy, Sara J.] Rancho Los Amigos Natl Rehabil Ctr, Pathokinesiol Lab, Downey, CA 90242 USA. [Mulroy, Sara J.] Univ So Calif, Herman Ostrow Sch Dent, Div Biokinesiol & Phys Therapy, Los Angeles, CA USA. [Kautz, Steven A.] Med Univ S Carolina, Coll Hlth Profess, Charleston, SC 29425 USA. [Kautz, Steven A.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Sullivan, Katherine J.] MetroHlth Stn Jefferson Pk BTL Hlth Inc, Los Angeles, CA USA. RP Mulroy, SJ (reprint author), Rancho Los Amigos Natl Rehabil Ctr, Pathokinesiol Lab, Downey, CA 90242 USA. NR 165 TC 0 Z9 0 U1 2 U2 8 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-62070-006-8 PY 2015 BP 384 EP 406 PG 23 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BB2VG UT WOS:000342391500024 ER PT B AU Cooper, RA Cooper, R Hill, K Karg, P Karmarkar, A Lane, AK Little, R Pelleschi, TL AF Cooper, Rory A. Cooper, Rosemarie Hill, Katya Karg, Patricia Karmarkar, Amol Lane, Amy Karas Little, Roger Pelleschi, Tamara L. BE Stein, J Harvey, RL Winstein, CJ Zorowitz, RD Wittenberg, GF TI Seating, Assistive Technology, and Equipment SO STROKE RECOVERY AND REHABILITATION, SECOND EDITION LA English DT Article; Book Chapter ID UNILATERAL NEGLECT; WHEELCHAIR; STROKE; LANGUAGE C1 [Cooper, Rory A.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15260 USA. [Cooper, Rory A.; Cooper, Rosemarie; Karg, Patricia; Lane, Amy Karas; Little, Roger] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Hill, Katya] AAC Inst, Pittsburgh, PA USA. [Karmarkar, Amol] Univ Texas Med Branch, Div Rehabil Sci, Galveston, TX 77555 USA. [Pelleschi, Tamara L.] Univ Pittsburgh, Hiram G Andrews Ctr, Johnstown, PA 15902 USA. RP Cooper, RA (reprint author), Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15260 USA. NR 42 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 978-1-62070-006-8 PY 2015 BP 623 EP 643 PG 21 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BB2VG UT WOS:000342391500038 ER PT B AU Shah, MV Hillinger, MG AF Shah, Monika V. Hillinger, Marni G. BE Stein, J Harvey, RL Winstein, CJ Zorowitz, RD Wittenberg, GF TI Sexuality After Stroke SO STROKE RECOVERY AND REHABILITATION, SECOND EDITION LA English DT Article; Book Chapter ID BILATERAL THALAMIC INFARCTION; URINARY-TRACT SYMPTOMS; TEMPORAL-LOBE EPILEPSY; POSTSTROKE DEPRESSION; ERECTILE DYSFUNCTION; DIABETIC MEN; DOUBLE-BLIND; HYPERTENSIVE MEN; BOTULINUM-TOXIN; BRAIN-LESIONS C1 [Shah, Monika V.] Mem Hermann Hosp, Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. [Shah, Monika V.] Mem Hermann Hosp, Brain Injury & Stroke Program, Inst Rehabil Res, Houston, TX USA. [Hillinger, Marni G.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Shah, MV (reprint author), Mem Hermann Hosp, Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. NR 95 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 978-1-62070-006-8 PY 2015 BP 819 EP 830 PG 12 WC Primary Health Care; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BB2VG UT WOS:000342391500050 ER PT B AU Handler, G Boninger, ML AF Handler, Grace Boninger, Michael L. BE Hammond, FM Malec, JF Nick, TG Buschbacher, RM TI Special Issues in Randomized Controlled Trials SO HANDBOOK FOR CLINICAL RESEARCH: DESIGN, STATISTICS, AND IMPLEMENTATION LA English DT Article; Book Chapter C1 [Handler, Grace] UPMC, UPMC Rehabil Inst, Pittsburgh, PA 15213 USA. [Boninger, Michael L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Boninger, Michael L.] VA Ctr Excellence Wheelchairs & Related Mobil, VA Pittsburgh Hlth Care Syst, Dept Vet Affairs, Pittsburgh, PA USA. RP Handler, G (reprint author), UPMC, UPMC Rehabil Inst, Pittsburgh, PA 15213 USA. NR 2 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 978-1-936287-54-3 PY 2015 BP 43 EP 45 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BB1YS UT WOS:000341461600012 ER PT B AU Qureshi, AA Walls, AC AF Qureshi, Abrar A. Walls, Andrew C. BE Rubin, DT Friedman, S Farrsye, FA TI MY PATIENT ON TUMOR NECROSIS FACTOR ALPHA THERAPY HAS A RASH. WHAT SHOULD I Do? SO CURBSIDE CONSULTATION IN IBD, SECOND EDITION SE Curbside Consultation in Gastroenterology LA English DT Article; Book Chapter C1 [Qureshi, Abrar A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Walls, Andrew C.] Boston Childrens Hosp, Massachusetts Gen Hosp, Harvard Combined Dermatol Residency Training Prog, Brigham & Womens Hosp,Beth Israel Hosp, Boston, MA USA. RP Qureshi, AA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 3 TC 0 Z9 0 U1 0 U2 3 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-034-4 J9 CURB CONSULT GASTROE PY 2015 BP 33 EP 38 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BB0KI UT WOS:000340342700008 ER PT B AU Bordeianou, L Hodin, R AF Bordeianou, Liliana Hodin, Richard BE Rubin, DT Friedman, S Farrsye, FA TI HOW DOES PERIOPERATIVE IMMUNE SUPPRESSION AFFECT SURGICAL OUTCOMES IN INFLAMMATORY BOWEL DISEASE? SO CURBSIDE CONSULTATION IN IBD, SECOND EDITION SE Curbside Consultation in Gastroenterology LA English DT Article; Book Chapter ID POSTOPERATIVE COMPLICATIONS; ULCERATIVE-COLITIS; CROHNS-DISEASE; INFLIXIMAB; RESECTION; INCREASE; THERAPY C1 [Bordeianou, Liliana; Hodin, Richard] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Bordeianou, L (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-034-4 J9 CURB CONSULT GASTROE PY 2015 BP 169 EP 172 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BB0KI UT WOS:000340342700037 ER PT J AU Kuchenbaecker, KB Neuhausen, SL Robson, M Barrowdale, D McGuffog, L Mulligan, AM Andrulis, IL Spurdle, AB Schmidt, MK Schmutzler, RK Engel, C Wappenschmidt, B Nevanlinna, H Thomassen, M Southey, M Radice, P Ramus, SJ Domchek, SM Nathanson, KL Lee, A Healey, S Nussbaum, RL Rebbeck, TR Arun, BK James, P Karlan, BY Lester, J Cass, I Terry, MB Daly, MB Goldgar, DE Buys, SS Janavicius, R Tihomirova, L Tung, N Dorfling, CM van Rensburg, EJ Steele, L Hansen, TVO Ejlertsen, B Gerdes, AM Nielsen, FC Dennis, J Cunningham, J Hart, S Slager, S Osorio, A Benitez, J Duran, M Weitzel, JN Tafur, I Hander, M Peterlongo, P Manoukian, S Peissel, B Roversi, G Scuvera, G Bonanni, B Mariani, P Volorio, S Dolcetti, R Varesco, L Papi, L Tibiletti, MG Giannini, G Fostira, F Konstantopoulou, I Garber, J Hamann, U Donaldson, A Brewer, C Foo, C Evans, DG Frost, D Eccles, D Douglas, F Brady, A Cook, J Tischkowitz, M Adlard, J Barwell, J Ong, KR Walker, L Izatt, L Side, LE Kennedy, MJ Rogers, MT Porteous, ME Morrison, PJ Platte, R Eeles, R Davidson, R Hodgson, S Ellis, S Godwin, AK Rhiem, K Meindl, A Ditsch, N Arnold, N Plendl, H Niederacher, D Sutter, C Steinemann, D Bogdanova-Markov, N Kast, K Varon-Mateeva, R Wang-Gohrke, S Gehrig, A Markiefka, B Buecher, B Lefol, C Stoppa-Lyonnet, D Rouleau, E Prieur, F Damiola, F Barjhoux, L Faivre, L Longy, M Sevenet, N Sinilnikova, OM Mazoyer, S Bonadona, V Caux-Moncoutier, V Isaacs, C Van Maerken, T Claes, K Piedmonte, M Andrews, L Hays, J Rodriguez, GC Caldes, T de la Hoya, M Khan, S Hogervorst, FBL Aalfs, CM de Lange, JL Meijers-Heijboer, HEJ van der Hout, AH Wijnen, JT van Roozendaal, KEP Mensenkamp, AR van den Ouweland, AMW van Deurzen, CHM van der Luijt, RB Olah, E Diez, O Lazaro, C Blanco, I Teule, A Menendez, M Jakubowska, A Lubinski, J Cybulski, C Gronwald, J Jaworska-Bieniek, K Durda, K Arason, A Maugard, C Soucy, P Montagna, M Agata, S Teixeira, MR Olswold, C Lindor, N Pankratz, VS Hallberg, E Wang, XS Szabo, CI Vijai, J Jacobs, L Corines, M Lincoln, A Berger, A Fink-Retter, A Singer, CF Rappaport, C Kaulich, DG Pfeiler, G Tea, MK Phelan, CM Mai, PL Greene, MH Rennert, G Imyanitov, EN Glendon, G Toland, AE Bojesen, A Pedersen, IS Jensen, UB Caligo, MA Friedman, E Berger, R Laitman, Y Rantala, J Arver, B Loman, N Borg, A Ehrencrona, H Olopade, OI Simard, J Easton, DF Chenevix-Trench, G Offit, K Couch, FJ Antoniou, AC AF Kuchenbaecker, Karoline B. Neuhausen, Susan L. Robson, Mark Barrowdale, Daniel McGuffog, Lesley Mulligan, Anna Marie Andrulis, Irene L. Spurdle, Amanda B. Schmidt, Marjanka K. Schmutzler, Rita K. Engel, Christoph Wappenschmidt, Barbara Nevanlinna, Heli Thomassen, Mads Southey, Melissa Radice, Paolo Ramus, Susan J. Domchek, Susan M. Nathanson, Katherine L. Lee, Andrew Healey, Sue Nussbaum, Robert L. Rebbeck, Timothy R. Arun, Banu K. James, Paul Karlan, Beth Y. Lester, Jenny Cass, Ilana Terry, Mary Beth Daly, Mary B. Goldgar, David E. Buys, Saundra S. Janavicius, Ramunas Tihomirova, Laima Tung, Nadine Dorfling, Cecilia M. van Rensburg, Elizabeth J. Steele, Linda Hansen, Thomas V. O. Ejlertsen, Bent Gerdes, Anne-Marie Nielsen, Finn C. Dennis, Joe Cunningham, Julie Hart, Steven Slager, Susan Osorio, Ana Benitez, Javier Duran, Mercedes Weitzel, Jeffrey N. Tafur, Isaac Hander, Mary Peterlongo, Paolo Manoukian, Siranoush Peissel, Bernard Roversi, Gaia Scuvera, Giulietta Bonanni, Bernardo Mariani, Paolo Volorio, Sara Dolcetti, Riccardo Varesco, Liliana Papi, Laura Tibiletti, Maria Grazia Giannini, Giuseppe Fostira, Florentia Konstantopoulou, Irene Garber, Judy Hamann, Ute Donaldson, Alan Brewer, Carole Foo, Claire Evans, D. Gareth Frost, Debra Eccles, Diana Douglas, Fiona Brady, Angela Cook, Jackie Tischkowitz, Marc Adlard, Julian Barwell, Julian Ong, Kai-ren Walker, Lisa Izatt, Louise Side, Lucy E. Kennedy, M. John Rogers, Mark T. Porteous, Mary E. Morrison, Patrick J. Platte, Radka Eeles, Ros Davidson, Rosemarie Hodgson, Shirley Ellis, Steve Godwin, Andrew K. Rhiem, Kerstin Meindl, Alfons Ditsch, Nina Arnold, Norbert Plendl, Hansjoerg Niederacher, Dieter Sutter, Christian Steinemann, Doris Bogdanova-Markov, Nadja Kast, Karin Varon-Mateeva, Raymonda Wang-Gohrke, Shan Gehrig, Andrea Markiefka, Birgid Buecher, Bruno Lefol, Cedrick Stoppa-Lyonnet, Dominique Rouleau, Etienne Prieur, Fabienne Damiola, Francesca Barjhoux, Laure Faivre, Laurence Longy, Michel Sevenet, Nicolas Sinilnikova, Olga M. Mazoyer, Sylvie Bonadona, Valerie Caux-Moncoutier, Virginie Isaacs, Claudine Van Maerken, Tom Claes, Kathleen Piedmonte, Marion Andrews, Lesley Hays, John Rodriguez, Gustavo C. Caldes, Trinidad de la Hoya, Miguel Khan, Sofia Hogervorst, Frans B. L. Aalfs, Cora M. de lange, J. L. Meijers-Heijboer, Hanne E. J. van der Hout, Annemarie H. Wijnen, Juul T. van Roozendaal, K. E. P. Mensenkamp, Arjen R. van den Ouweland, Ans M. W. van Deurzen, Carolien H. M. van der Luijt, Rob B. Olah, Edith Diez, Orland Lazaro, Conxi Blanco, Ignacio Teule, Alex Menendez, Mireia Jakubowska, Anna Lubinski, Jan Cybulski, Cezary Gronwald, Jacek Jaworska-Bieniek, Katarzyna Durda, Katarzyna Arason, Adalgeir Maugard, Christine Soucy, Penny Montagna, Marco Agata, Simona Teixeira, Manuel R. Olswold, Curtis Lindor, Noralane Pankratz, Vernon S. Hallberg, Emily Wang, Xianshu Szabo, Csilla I. Vijai, Joseph Jacobs, Lauren Corines, Marina Lincoln, Anne Berger, Andreas Fink-Retter, Anneliese Singer, Christian F. Rappaport, Christine Kaulich, Daphne Gschwantler Pfeiler, Georg Tea, Muy-Kheng Phelan, Catherine M. Mai, Phuong L. Greene, Mark H. Rennert, Gad Imyanitov, Evgeny N. Glendon, Gord Toland, Amanda Ewart Bojesen, Anders Pedersen, Inge Sokilde Jensen, Uffe Birk Caligo, Maria A. Friedman, Eitan Berger, Raanan Laitman, Yael Rantala, Johanna Arver, Brita Loman, Niklas Borg, Ake Ehrencrona, Hans Olopade, Olufunmilayo I. Simard, Jacques Easton, Douglas F. Chenevix-Trench, Georgia Offit, Kenneth Couch, Fergus J. Antoniou, Antonis C. CA Breast Canc Family Registry EMBRACE Study GEMO Study Collaborators HEBON KConFab Investigators CIMBA TI Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers SO BREAST CANCER RESEARCH LA English DT Article AB Introduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative-(TN) status; morphologic subtypes; histological grade; and nodal involvement. Results: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive associations in the general population (intraclass correlation (ICC) = 0.61, 95% confidence interval (CI): 0.45 to 0.74), and the same was true when considering ER-negative associations in both groups (ICC = 0.59, 95% CI: 0.42 to 0.72). Similarly, there was strong correlation between the ER-positive associations for BRCA1 and BRCA2 carriers (ICC = 0.67, 95% CI: 0.52 to 0.78), whereas ER-positive associations in any one of the groups were generally inconsistent with ER-negative associations in any of the others. After stratifying by ER status in mutation carriers, additional significant associations were observed. Several previously unreported variants exhibited associations at P < 10-6 in the analyses by PR status, HER2 status, TN phenotype, morphologic subtypes, histological grade and nodal involvement. Conclusions: Differences in associations of common BC susceptibility alleles between BRCA1 and BRCA2 carriers and the general population are explained to a large extent by differences in the prevalence of ER-positive and ER-negative tumors. 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[Diez, Orland] Univ Autonoma Barcelona, Barcelona, Spain. [Lazaro, Conxi; Menendez, Mireia] IDIBELL Catalan Inst Oncol, Hereditary Canc Program, Mol Diagnost Unit, Barcelona, Spain. [Blanco, Ignacio; Teule, Alex] IDIBELL Catalan Inst Oncol, Hereditary Canc Program, Genet Counseling Unit, Barcelona, Spain. [Jakubowska, Anna; Lubinski, Jan; Cybulski, Cezary; Gronwald, Jacek; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland. [Arason, Adalgeir] Univ Iceland, Landspitali Univ Hosp, Dept Pathol, Fac Med, Reykjavik, Iceland. [Arason, Adalgeir] Univ Iceland, BMC, Fac Med, Reykjavik, Iceland. [Maugard, Christine] Hop Univ Strasbourg, CHRU Nouvel Hop Civil, Lab Diagnost Genet, Strasbourg, France. [Maugard, Christine] Hop Univ Strasbourg, CHRU Nouvel Hop Civil, Serv Oncohematol, Strasbourg, France. [Soucy, Penny; Simard, Jacques] Ctr Hosp Univ Quebec, Res Ctr, Quebec City, PQ, Canada. [Soucy, Penny; Simard, Jacques] Univ Laval, Quebec City, PQ, Canada. [Montagna, Marco; Agata, Simona] IRCCS, Ist Oncol Veneto, Immunol & Mol Oncol Unit, Padua, Italy. [Teixeira, Manuel R.] Portuguese Oncol Inst, Dept Genet, Oporto, Portugal. [KConFab Investigators] Peter MacCallum Canc Ctr, kConFab Kathleen Cuningham Consortium Res Familia, Melbourne, Vic, Australia. [Lindor, Noralane] Mayo Clin, Hlth Sci Res, Scottsdale, AZ USA. [Wang, Xianshu] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Szabo, Csilla I.] NHGRI, NIH, Bethesda, MD 20892 USA. [Jacobs, Lauren; Corines, Marina; Lincoln, Anne] Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, New York, NY 10021 USA. [Berger, Andreas; Fink-Retter, Anneliese; Rappaport, Christine; Kaulich, Daphne Gschwantler; Pfeiler, Georg; Tea, Muy-Kheng] Med Univ Vienna, Dept Obstet & Gynecol, Vienna, Austria. [Berger, Andreas; Fink-Retter, Anneliese; Singer, Christian F.; Rappaport, Christine; Kaulich, Daphne Gschwantler; Pfeiler, Georg; Tea, Muy-Kheng] Med Univ Vienna, Ctr Comprehens Canc, Vienna, Austria. [Phelan, Catherine M.] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA. [Mai, Phuong L.; Greene, Mark H.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Rennert, Gad] Clalit Natl Israeli Canc Control Ctr, Haifa, Israel. [Rennert, Gad] Carmel Hosp, Dept Community Med & Epidemiol, Haifa, Israel. [Rennert, Gad] B Rappaport Fac Med, Haifa, Israel. [Imyanitov, Evgeny N.] NN Petrov Inst Oncol, St Petersburg, Russia. [Glendon, Gord] Mt Sinai Hosp, Canc Care Ontario, Ontario Canc Genet Network, Samuel Lunenfeld Res Inst, Toronto, ON, Canada. [Toland, Amanda Ewart] Ohio State Univ, Ctr Comprehens Canc, Div Human Canc Genet, Dept Internal Med & Mol Virol, Columbus, OH 43210 USA. [Toland, Amanda Ewart] Ohio State Univ, Ctr Comprehens Canc, Dept Immunol & Med Genet, Columbus, OH 43210 USA. [Bojesen, Anders] Vejle Hosp, Dept Clin Genet, Vejle, Denmark. [Pedersen, Inge Sokilde] Aalborg Univ Hosp, Dept Biochem, Sect Mol Diagnost, Aalborg, Denmark. [Jensen, Uffe Birk] Aarhus Univ Hosp, Dept Clin Genet, Aarhus N, Denmark. [Caligo, Maria A.] Univ Pisa, Dept Lab Med, Sect Genet Oncol, Pisa, Italy. [Caligo, Maria A.] Univ Hosp Pisa, Pisa, Italy. [Friedman, Eitan; Berger, Raanan; Laitman, Yael] Sheba Med Ctr, Tel Aviv, Israel. [Rantala, Johanna] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden. [Arver, Brita] Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden. [Loman, Niklas] Univ Lund Hosp, Dept Oncol, Lund, Sweden. [Borg, Ake] Lund Univ, Dept Oncol, Lund, Sweden. Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden. Univ Lund Hosp, Dept Clin Genet, Lund, Sweden. [Ehrencrona, Hans] Univ Chicago, Med Ctr, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA. [Ehrencrona, Hans] Univ Lund Hosp, Dept Clin Genet, Lund, Sweden. RP Kuchenbaecker, KB (reprint author), Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. EM kbk21@medschl.cam.ac.uk RI Giannini, Giuseppe/B-5672-2013; montagna, marco/E-2225-2012; Mensenkamp, A.R./L-4520-2015; Jansen van Rensburg, Elizabeth (Lizette)/B-9104-2011; Gronwald, Jacek/A-4576-2017; manoukian, siranoush/E-7132-2017; Peissel, Bernard/E-8187-2017; Spurdle, Amanda/A-4978-2011; Menendez Vila, Mireia/H-9981-2015; OI Giannini, Giuseppe/0000-0003-0299-4056; Blanco, Ignacio/0000-0002-7414-7481; Ramus, Susan/0000-0003-0005-7798; montagna, marco/0000-0002-4929-2150; Gronwald, Jacek/0000-0002-3643-2871; manoukian, siranoush/0000-0002-6034-7562; Peissel, Bernard/0000-0001-9233-3571; Eeles, Rosalind/0000-0002-3698-6241; Spurdle, Amanda/0000-0003-1337-7897; Barrowdale, Daniel/0000-0003-1661-3939; Dolcetti, Riccardo/0000-0003-1625-9853; Papi, Laura/0000-0003-4552-9517; Menendez Vila, Mireia/0000-0001-8050-0803; Ehrencrona, Hans/0000-0002-5589-3622; Khan, Sofia/0000-0003-4185-8882; Evans, Gareth/0000-0002-8482-5784 FU Cancer Research UK grant [C12292/A11174]; European Community's Seventh Framework Programme (COGS) [223175 (HEALTH-F2-2009-223175)]; Cancer Research UK [C12292/A11174, C1287/A10118, C1287/A 10710, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692]; National Institutes of Health [CA128978, 5U01 CA113916, R01 CA140323]; Post-Cancer GWAS initiative (Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative) [1U19 CA148537, 1U19 CA148065, 1U19 CA148112]; US Department of Defense [W81XWH-10-1-0341]; Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer; Komen Foundation for the Cure; Breast Cancer Research Foundation; Ovarian Cancer Research Fund; National Cancer Institute [UM1 CA164920, RC4CA153828, CA 27469, CA 37517, CA 101165]; Lithuania (BFBOCC-LT): Research Council of Lithuania [LIG-07/2012]; LSC grant [10.0010.08]; ESF [2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016]; Liepaja's municipal council; Cancer Association of South Africa (CANSA); Morris and Horowitz Families Endowed Professorship; NEYE Foundation; Spanish Association against Cancer [AECC08]; RTICC [06/0020/1060, FISPI12/00070]; Mutua Madrilena Foundation (FMMA); Office of the Director, National Institutes of Health; Fondazione IRCCS Istituto Nazionale Tumori; IRCCS AOU San Martino; IST Istituto Nazionale per la Ricerca sul Cancro; Italian Association for Cancer Research (AIRC); Associazione CAOS-Varese; NHMRC Program Grant; European Union (European Social Fund (ESF)); Greek national funds through Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF); Research Funding Program of the General Secretariat for Research & Technology: ARISTEIA; DKFZ; Cancer Research UK grants [C1287/A10118, C1287/A16563, C1287/A17523, C5047/A8385]; NIHR grant; University of Kansas Cancer Center [P30 CA168524]; Kansas Bioscience Authority Eminent Scholar Program; Chancellors Distinguished Chair in Biomedical Sciences Professorship; German Cancer Aid [109076]; Center for Molecular Medicine Cologne (CMMC); Ligue National Contre le Cancer; Association "Le cancer du sein, parlons-en!" Award; Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program; National Cancer Institute; NCI Intramural Research Program; ISCIII (Spain) [RD12/00369/0006, 12/00539]; European Regional Development FEDER funds; Helsinki University Central Hospital Research Fund, Academy of Finland [266528]; Finnish Cancer Society; Sigrid Juselius Foundation; Dutch Cancer Society grants [NKI1998-1854, NKI2004-3088, NKI2007-3756]; Netherlands Organization of Scientific Research grant [NWO 91109024]; Pink Ribbon grant [110005]; BBMRI grant [NWO 184.021.007/CP46]; Hong Kong Hereditary Breast Cancer Family Registry; Dr Ellen Li Charitable Foundation, Hong Kong; Hungarian Research Grants [KTIA-OTKA CK-80745, OTKA K-112228]; Asociacion Espanola Contra el Cancer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia; ISCIIIRETIC [RD06/0020/1051, RD12/0036/008, PI10/01422, PI10/00748, PI13/00285, 2009SGR290]; Icelandic Association "Walking for Breast Cancer Research"; Landspitali University Hospital Research Fund; Canadian Breast Cancer Research Alliance grant [019511]; Ministry of Economic Development, Innovation and Export Trade grant [PSR-SIIRI-701]; Ministero della Salute; "5 x 1000" Istituto Oncologico Veneto grant; Liga Portuguesa Contra o Cancro; National Breast Cancer Foundation; National Health and Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer Councils of New South Wales, Victoria, Tasmania and South Australia; Cancer Foundation of Western Australia; NHMRC Research Fellowship scheme; National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea [1020350]; NIH grant [CA128978]; NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201, CA125183, R01 CA142996, 1U01 CA161032]; US Department of Defense Ovarian Cancer Idea award [W81XWH-10-1-0341]; MH CZ - DRO (MMCI) [00209805]; European Regional Development Fund; State Budget of the Czech Republic (RECAMO) [CZ. 1.05/2.1.00/03.0101]; Charles University in Prague project [UNCE204024]; Robert and Kate Niehaus Clinical Cancer Genetics Initiative [1R01 CA149429-01]; Intramural Research Program of the US National Cancer Institute, NIH; Westat (Rockville, MD, USA) [N02-CP-11019-50, N02-CP-65504]; Clalit Health Services in Israel; Israel Cancer Association; Breast Cancer Research Foundation (BCRF), New York; Russian Foundation for Basic Research [13-04-92613]; Ohio State University Comprehensive Cancer Center; ITT (Istituto Toscano Tumori) grants [2011-2013]; Ministry of Science, Technology and Innovation, Ministry of Higher Education [UM.C/HlR/MOHE/06]; Cancer Research Initiatives Foundation; Israeli Inherited breast cancer consortium; Swedish Cancer Society; Ralph and Marion Falk Medical Research Trust; Entertainment Industry Fund National Women's Cancer Research Alliance; CRUK; American Cancer Society Early Detection Professorship [SIOP-06-258-01-COUN]; [PBZ_KBN_122/P05/2004] FX The CIMBA data management and analysis are funded through Cancer Research UK grant C12292/A11174. ACA is a Senior Cancer Research UK Research Fellow. Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112: the Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative), the US Department of Defense (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. This work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US government or the BCFR. This work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this article does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US government or the BCFR. This work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US government or the BCFR. BFBOCC is partly supported by: Lithuania (BFBOCC-LT): Research Council of Lithuania grant LIG-07/2012; Latvia (BFBOCC-LV) is partly supported by LSC grant 10.0010.08 and in part by a grant from the ESF 2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016 and Liepaja's municipal council.; BIDMC is supported by the Breast Cancer Research Foundation. BRCA-gene mutations and breast cancer in South African women (BMBSA) was supported by grants from the Cancer Association of South Africa (CANSA) to Elizabeth J van Rensburg. SLN was partially supported by the Morris and Horowitz Families Endowed Professorship. This work was supported by the NEYE Foundation. The CNIO study was supported by Spanish Association against Cancer (AECC08), RTICC 06/0020/1060 and FISPI12/00070 and Mutua Madrilena Foundation (FMMA). City of Hope Clinical Cancer Genetics Community Network and the Hereditary Cancer Research Registry, supported in part by Award Number RC4CA153828 (Principal Investigator: J Weitzel) from the National Cancer Institute and the Office of the Director, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funds from Italian citizens who allocated the "5 x 1000" share of their tax payment, according to Italian laws, in support of the Fondazione IRCCS Istituto Nazionale Tumori (to SM), and of IRCCS AOU San Martino, IST Istituto Nazionale per la Ricerca sul Cancro (to LV); Italian Association for Cancer Research (AIRC) to GG; Associazione CAOS-Varese (to MGT). SH is supported by an NHMRC Program Grant (to GCT). GCT is an NHMRC Senior Principal Research Fellow. This research has been cofinanced by the European Union (European Social Fund (ESF)) and Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF), Research Funding Program of the General Secretariat for Research & Technology: ARISTEIA, investing in knowledge society through the European Social Fund. The DKFZ study was supported by the DKFZ. EMBRACE is supported by Cancer Research UK grants C1287/A10118, C1287/A16563 and C1287/A17523. D Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester. The investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft are supported by Cancer Research UK grant C5047/A8385. The authors acknowledge support from The University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program. AKG was funded by grants 5U01 CA113916, R01 CA140323 from the National Institutes of Health and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship. The German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC) is supported by the German Cancer Aid (grant no 109076, Rita K Schmutzler) and by the Center for Molecular Medicine Cologne (CMMC). The study was supported by the Ligue National Contre le Cancer; the Association "Le cancer du sein, parlons-en!" Award; and the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program. Tom Van Maerken is senior clinical investigator of FWO. This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office and Tissue Bank (CA 27469), the GOG Statistical and Data Center (CA 37517), and GOG's Cancer Prevention and Control Committee (CA 101165). Drs Greene, Mai and Savage were supported by funding from the NCI Intramural Research Program.; HCSC was supported by a grant RD12/00369/0006 and 12/00539 from ISCIII (Spain), partially supported by European Regional Development FEDER funds. The HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society and the Sigrid Juselius Foundation. The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organization of Scientific Research grant NWO 91109024, the Pink Ribbon grant 110005 and the BBMRI grant NWO 184.021.007/CP46. HEBON thanks the registration teams of the Comprehensive Cancer Centre Netherlands and Comprehensive Centre South (together the Netherlands Cancer Registry) and PALGA (Dutch Pathology Registry) for part of the data collection. HRBCP is supported by The Hong Kong Hereditary Breast Cancer Family Registry and the Dr Ellen Li Charitable Foundation, Hong Kong.; The Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research Grants KTIA-OTKA CK-80745 and OTKA K-112228. ICO: Contract grant sponsor: Asociacion Espanola Contra el Cancer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia. Contract grants ISCIIIRETIC RD06/0020/1051, RD12/0036/008, PI10/01422, PI10/00748, PI13/00285 and 2009SGR290. The IHCC was supported by Grant PBZ_KBN_122/P05/2004. The ILUH group was supported by the Icelandic Association "Walking for Breast Cancer Research" and by the Landspitali University Hospital Research Fund. This work was supported by the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program, Canadian Breast Cancer Research Alliance grant 019511 and Ministry of Economic Development, Innovation and Export Trade grant PSR-SIIRI-701. IOVHBOCS is supported by Ministero della Salute and "5 x 1000" Istituto Oncologico Veneto grant. This study was in part supported by Liga Portuguesa Contra o Cancro. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. GCT and ABS are supported by the NHMRC Research Fellowship scheme. KOHBRA is supported by a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea (1020350). MAYO is supported by NIH grant CA128978, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a US Department of Defense Ovarian Cancer Idea award (W81XWH-10-1-0341) and a grant from the Breast Cancer Research Foundation. Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation and Export Trade. MODSQUAD was supported by MH CZ - DRO (MMCI, 00209805) and by the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ. 1.05/2.1.00/03.0101) (to LF), and by Charles University in Prague project UNCE204024 (MZ). MSKCC is supported by grants from the Breast Cancer Research Foundation and Robert and Kate Niehaus Clinical Cancer Genetics Initiative 1R01 CA149429-01. The research of MH Greene and PL Mai was supported by the Intramural Research Program of the US National Cancer Institute, NIH, and by support services contracts N02-CP-11019-50 and N02-CP-65504 with Westat (Rockville, MD, USA). NICCC is supported by Clalit Health Services in Israel. Some of its activities are supported by the Israel Cancer Association and the Breast Cancer Research Foundation (BCRF), New York. This work has been supported by the Russian Foundation for Basic Research (grant 13-04-92613).; This work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US government or the BCFR. OSUCCG is supported by The Ohio State University Comprehensive Cancer Center. This work was supported by the ITT (Istituto Toscano Tumori) grants 2011-2013; the Ministry of Science, Technology and Innovation, Ministry of Higher Education (UM.C/HlR/MOHE/06); and the Cancer Research Initiatives Foundation. This project was partially funded through a grant by the Israel cancer association and the funding for the Israeli Inherited breast cancer consortium.; SWE-BRCA collaborators are supported by the Swedish Cancer Society. UCHICAGO is supported by NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996, 1U01 CA161032 and by the Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women's Cancer Research Alliance and the Breast Cancer Research Foundation. OIO is an ACS Clinical Research Professor. Jonsson Comprehensive Cancer Center Foundation; Breast Cancer Research Foundation. UCSF Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center. UKFOCR was supported by a project grant from CRUK to Paul Pharoah. National Institutes of Health (NIH) (R01 CA102776 and R01 CA083855; Breast Cancer Research Foundation; Susan G Komen Foundation for the cure, Basser Research Center for BRCA. Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation. The Women's Cancer Program (WCP) at the Samuel Oschin Comprehensive Cancer Institute is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN). NR 26 TC 4 Z9 4 U1 10 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PD DEC 31 PY 2014 VL 16 AR 3416 DI 10.1186/s13058-014-0492-9 PG 27 WC Oncology SC Oncology GA V44TY UT WOS:000209772500001 PM 25919761 ER PT J AU Sharifnia, T Rusu, V Piccioni, F Bagul, M Imielinski, M Cherniack, AD Pedamallu, CS Wong, B Wilson, FH Garraway, LA Altshuler, D Golub, TR Root, DE Subramanian, A Meyerson, M AF Sharifnia, Tanaz Rusu, Victor Piccioni, Federica Bagul, Mukta Imielinski, Marcin Cherniack, Andrew D. Pedamallu, Chandra Sekhar Wong, Bang Wilson, Frederick H. Garraway, Levi A. Altshuler, David Golub, Todd R. Root, David E. Subramanian, Aravind Meyerson, Matthew TI Genetic modifiers of EGFR dependence in non-small cell lung cancer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE epidermal growth factor receptor; non-small cell lung cancer; ORF ID GROWTH-FACTOR RECEPTOR; ACQUIRED-RESISTANCE; C-SRC; ERLOTINIB RESISTANCE; KINASE INHIBITORS; TYROSINE KINASES; TARGETED THERAPY; WILD-TYPE; GEFITINIB; MUTATIONS AB Lung adenocarcinomas harboring activating mutations in the epidermal growth factor receptor (EGFR) represent a common molecular subset of non-small cell lung cancer (NSCLC) cases. EGFR mutations predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs) and thus represent a dependency in NSCLCs harboring these alterations, but the genetic basis of EGFR dependence is not fully understood. Here, we applied an unbiased, ORF-based screen to identify genetic modifiers of EGFR dependence in EGFR-mutant NSCLC cells. This approach identified 18 kinase and kinase-related genes whose overexpression can substitute for EGFR in EGFR-dependent PC9 cells, and these genes include seven of nine Src family kinase genes, FGFR1, FGFR2, ITK, NTRK1, NTRK2, MOS, MST1R, and RAF1. A subset of these genes can complement loss of EGFR activity across multiple EGFR-dependent models. Unbiased gene-expression profiling of cells overexpressing EGFR bypass genes, together with targeted validation studies, reveals EGFR-independent activation of the MEK-ERK and phosphoinositide 3-kinase (PI3K)-AKT pathways. Combined inhibition of PI3K-mTOR and MEK restores EGFR dependence in cells expressing each of the 18 EGFR bypass genes. Together, these data uncover a broad spectrum of kinases capable of overcoming dependence on EGFR and underscore their convergence on the PI3K-AKT and MEK-ERK signaling axes in sustaining EGFR-independent survival. C1 [Sharifnia, Tanaz; Rusu, Victor; Piccioni, Federica; Bagul, Mukta; Imielinski, Marcin; Cherniack, Andrew D.; Pedamallu, Chandra Sekhar; Wong, Bang; Wilson, Frederick H.; Garraway, Levi A.; Altshuler, David; Golub, Todd R.; Root, David E.; Subramanian, Aravind; Meyerson, Matthew] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Sharifnia, Tanaz; Imielinski, Marcin; Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Rusu, Victor; Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Sharifnia, Tanaz; Imielinski, Marcin; Pedamallu, Chandra Sekhar; Wilson, Frederick H.; Garraway, Levi A.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Altshuler, David] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. RP Meyerson, M (reprint author), Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. EM matthew_meyerson@dfci.harvard.edu FU National Cancer Institute [R01CA116020, R01CA109038, P50CA090578]; National Institutes of Health [5U54HG006093] FX We thank the Broad Genetic Perturbation Platform for generation of the ORF library; the Broad Connectivity Map team for generation of the Library of Integrated Network- Based Cellular Signatures (LINCS) dataset and technical assistance; V. Dancik for LINCS compound identification; and J. Chmielecki, H. Greulich, E. Stover, Z. Tothova, and X. Wu for helpful discussions. Support for this work was provided by National Cancer Institute Grants R01CA116020, R01CA109038, and P50CA090578 (to M.M.) and National Institutes of Health Common Fund Grant 5U54HG006093 (to T.R.G.). NR 36 TC 11 Z9 12 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 30 PY 2014 VL 111 IS 52 BP 18661 EP 18666 DI 10.1073/pnas.1412228112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY2UL UT WOS:000347444400063 PM 25512530 ER PT J AU Garzon, R Volinia, S Papaioannou, D Nicolet, D Kohlschmidt, J Yan, PS Mrozek, K Bucci, D Carroll, AJ Baer, MR Wetzler, M Carter, TH Powell, BL Kolitz, JE Moore, JO Eisfeld, AK Blachly, JS Blum, W Caligiuria, MA Stone, RM Marcucci, G Croce, CM Byrd, JC Bloomfield, CD AF Garzon, Ramiro Volinia, Stefano Papaioannou, Dimitrios Nicolet, Deedra Kohlschmidt, Jessica Yan, Pearlly S. Mrozek, Krzysztof Bucci, Donna Carroll, Andrew J. Baer, Maria R. Wetzler, Meir Carter, Thomas H. Powell, Bayard L. Kolitz, Jonathan E. Moore, Joseph O. Eisfeld, Ann-Kathrin Blachly, James S. Blum, William Caligiuria, Michael A. Stone, Richard M. Marcucci, Guido Croce, Carlo M. Byrd, John C. Bloomfield, Clara D. TI Expression and prognostic impact of lncRNAs in acute myeloid leukemia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE lncRNAs; acute myeloid leukemia; outcome ID NONCODING RNA HOTAIR; OLDER PATIENTS; MICRORNA-EXPRESSION; GROUP-B; COLORECTAL CANCERS; POOR-PROGNOSIS; RETINOIC ACID; DISTINCT GENE; MUTATIONS; CYTOGENETICS AB Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides, located within the intergenic stretches or overlapping antisense transcripts of protein coding genes. LncRNAs are involved in numerous biological roles including imprinting, epigenetic regulation, apoptosis, and cell cycle. To determine whether lncRNAs are associated with clinical features and recurrent mutations in older patients (aged >= 60 y) with cytogenetically normal (CN) acute myeloid leukemia (AML), we evaluated lncRNA expression in 148 untreated older CN-AML cases using a custom microarray platform. An independent set of 71 untreated older patients with CN-AML was used to validate the outcome scores using RNA sequencing. Distinctive lncRNA profiles were found associated with selected mutations, such as internal tandem duplications in the FLT3 gene (FLT3-ITD) and mutations in the NPM1, CEBPA, IDH2, ASXL1, and RUNX1 genes. Using the lncRNAs most associated with event-free survival in a training cohort of 148 older patients with CN-AML, we derived a lncRNA score composed of 48 lncRNAs. Patients with an unfavorable compared with favorable lncRNA score had a lower complete response (CR) rate [P < 0.001, odds ratio = 0.14, 54% vs. 89%], shorter disease-free survival (DFS) [P < 0.001, hazard ratio (HR) = 2.88] and overall survival (OS) (P < 0.001, HR = 2.95). The validation set analyses confirmed these results (CR, P = 0.03; DFS, P = 0.009; OS, P = 0.009). Multivariable analyses for CR, DFS, and OS identified the lncRNA score as an independent marker for outcome. In conclusion, lncRNA expression in AML is closely associated with recurrent mutations. A small subset of lncRNAs is correlated strongly with treatment response and survival. C1 [Garzon, Ramiro; Papaioannou, Dimitrios; Nicolet, Deedra; Kohlschmidt, Jessica; Yan, Pearlly S.; Mrozek, Krzysztof; Bucci, Donna; Eisfeld, Ann-Kathrin; Blachly, James S.; Blum, William; Caligiuria, Michael A.; Marcucci, Guido; Croce, Carlo M.; Byrd, John C.; Bloomfield, Clara D.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Volinia, Stefano] Univ Ferrara, Dept Morphol Surg & Expt Med, I-44121 Ferrara, FE, Italy. [Nicolet, Deedra; Kohlschmidt, Jessica] Mayo Clin, Oncol Stat & Data Ctr, Alliance Clin Trials, Rochester, MN 55905 USA. [Carroll, Andrew J.] Univ Alabama Birmingham, Dept Genet, Birmingham, AL 35294 USA. [Baer, Maria R.] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Wetzler, Meir] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Carter, Thomas H.] Univ Iowa, Holden Comprehens Canc Ctr, Iowa City, IA 52242 USA. [Powell, Bayard L.] Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27157 USA. [Kolitz, Jonathan E.] North Shore Canc Inst, Lake Success, NY 11042 USA. [Moore, Joseph O.] Duke Univ, Dept Med, Div Hematol Oncol, Durham, NC 27701 USA. [Moore, Joseph O.] Durham VA Med Ctr, Durham, NC 27701 USA. [Stone, Richard M.] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Garzon, R (reprint author), Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. EM ramiro.garzon@osumc.edu; carlo.croce@osumc.edu; clara.bloomfield@osumc.edu RI Garzon, Ramiro/E-3104-2011; Mrozek, Krzysztof/A-3142-2008; Yan, Pearlly/E-4339-2011; OI Yan, Pearlly/0000-0003-1965-4920; Blachly, James/0000-0002-4275-5562; Volinia, Stefano/0000-0003-0910-3893 FU National Cancer Institute [P50-CA140158-05, CA101140, CA180861]; Brigham and Women's Hospital [BWH 108415, 110414]; Coleman Leukemia Research Foundation; Pelotonia Fellowship Program; Associazione Italiana Ricerca sul Cancro [IG 13585]; Ministero della Istruzione Universita e Ricerca FX This work was supported in part by the National Cancer Institute Grants P50-CA140158-05 (to R.G., W.B., G.M., J.C.B., and C.D.B.), CA101140 (to G.M., C.D.B., and M.A.C.), CA180861 (to G.M., and C.D.B.), Brigham and Women's Hospital BWH 108415 and 110414 (to M.A.C. and G.M.), the Coleman Leukemia Research Foundation, and the Pelotonia Fellowship Program (A.-K.E.). S.V. was supported by Associazione Italiana Ricerca sul Cancro (IG 13585), and Ministero della Istruzione Universita e Ricerca (PRIN 2010). NR 49 TC 49 Z9 51 U1 3 U2 17 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 30 PY 2014 VL 111 IS 52 BP 18679 EP 18684 DI 10.1073/pnas.1422050112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY2UL UT WOS:000347444400066 PM 25512507 ER PT J AU Li, YC Hadden, C Singh, P Mercado, CP Murphy, P Dajani, NK Lowery, CL Roberts, DJ Maroteaux, L Kilic, F AF Li, Yicong Hadden, Coedy Singh, Preeti Mercado, Charles P. Murphy, Pamela Dajani, Nafisa K. Lowery, Curtis L. Roberts, Drucilla J. Maroteaux, Luc Kilic, Fusun TI GDM-associated insulin deficiency hinders the dissociation of SERT from ERp44 and down-regulates placental 5-HT uptake SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE serotonin; ERp44; insulin; serotonin transporter; gestational diabetes mellitus ID GESTATIONAL-DIABETES-MELLITUS; BRAIN-SEROTONIN TRANSPORTER; MEDIATED PROTEIN RETENTION; VILLOUS TROPHOBLAST CELLS; HUMAN TERM PLACENTAE; ENDOPLASMIC-RETICULUM; SIALIC-ACID; CARBOHYDRATE-METABOLISM; DOPAMINE TRANSPORTER; PLASMA SEROTONIN AB Serotonin (5-HT) transporter (SERT) regulates the level of 5-HT in placenta. Initially, we found that in gestational diabetes mellitus (GDM), whereas free plasma 5-HT levels were elevated, the 5-HT uptake rates of trophoblast were significantly down-regulated, due to impairment in the translocation of SERT molecules to the cell surface. We sought to determine the factors mediating the down-regulation of SERT in GDM trophoblast. We previously reported that an endoplasmic reticulum chaperone, ERp44, binds to Cys200 and Cys209 residues of SERT to build a disulfide bond. Following this posttranslational modification, before trafficking to the plasma membrane, SERT must be dissociated from ERp44; and this process is facilitated by insulin signaling and reversed by the insulin receptor blocker AGL2263. However, the GDM-associated defect in insulin signaling hampers the dissociation of ERp44 from SERT. Furthermore, whereas ERp44 constitutively occupies Cys200/Cys209 residues, one of the SERT glycosylation sites, Asp208 located between the two Cys residues, cannot undergo proper glycosylation, which plays an important role in the uptake efficiency of SERT. Herein, we show that the decrease in 5-HT uptake rates of GDM trophoblast is the consequence of defective insulin signaling, which entraps SERT with ERp44 and impairs its glycosylation. In this regard, restoring the normal expression of SERT on the trophoblast surface may represent a novel approach to alleviating some GDM-associated complications. C1 [Li, Yicong; Hadden, Coedy; Singh, Preeti; Mercado, Charles P.; Kilic, Fusun] Univ Arkansas Med Sci, Coll Med, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. [Murphy, Pamela; Dajani, Nafisa K.; Lowery, Curtis L.] Univ Arkansas Med Sci, Coll Med, Dept Obstet & Gynecol, Little Rock, AR 72205 USA. [Roberts, Drucilla J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Maroteaux, Luc] Inst Fer A Moulin, INSERM, UMR S 839, F-75005 Paris, France. RP Kilic, F (reprint author), Univ Arkansas Med Sci, Coll Med, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. EM kilicfusun@UAMS.edu; kilicfusun@UAMS.edu OI Maroteaux, Luc/0000-0002-9499-8603 FU Centre National de la Recherche Scientifique; Institut National de la Sante et de la Recherche Medicale; Universite Pierre et Marie Curie; Fondation de France; Fondation pour la Recherche Medicale [FRM DEQ2014039529]; French Ministry of Research (Agence Nationale pour la Recherche) [ANR-12-BSV1-0015-01]; ANR [ANR-11-IDEX-0004-02]; NIH Child Health and Human Development [HD058697, HD053477]; Heart Lung and Blood Institute Grant [HL091196]; American Heart Association [13GRNT17240014]; Minnie Merrill Sturgis Diabetes Research Fund; Sturgis Charitable Trust; AHA predoctoral fellowship [14PRE20500039] FX We gratefully acknowledge the UAMS Flow Cytometry Core and thank Ms. Amber Ward for assistance in obtaining consents from subjects and providing us the samples. L.M.'s work was supported by funds from the Centre National de la Recherche Scientifique, the Institut National de la Sante et de la Recherche Medicale, the Universite Pierre et Marie Curie, and by grants from the Fondation de France, the Fondation pour la Recherche Medicale "Equipe FRM DEQ2014039529", the French Ministry of Research (Agence Nationale pour la Recherche) ANR-12-BSV1-0015-01, and the Investissements d'Avenir program managed by the ANR under reference ANR-11-IDEX-0004-02. This work was supported by NIH Child Health and Human Development Grants HD058697 and HD053477, Heart Lung and Blood Institute Grant HL091196, American Heart Association [13GRNT17240014], the Minnie Merrill Sturgis Diabetes Research Fund, and the Sturgis Charitable Trust (F.K.). Y.L. is supported by AHA predoctoral fellowship 14PRE20500039. NR 77 TC 7 Z9 7 U1 2 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 30 PY 2014 VL 111 IS 52 BP E5697 EP E5705 DI 10.1073/pnas.1416675112 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY2UL UT WOS:000347444400015 PM 25512553 ER PT J AU Marco, E Karp, RL Guo, GJ Robson, P Hart, AH Trippa, L Yuan, GC AF Marco, Eugenio Karp, Robert L. Guo, Guoji Robson, Paul Hart, Adam H. Trippa, Lorenzo Yuan, Guo-Cheng TI Bifurcation analysis of single-cell gene expression data reveals epigenetic landscape SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE single cell; gene expression; bifurcation; differentiation ID EMBRYONIC STEM-CELLS; RNA-SEQ; LINEAGE-COMMITMENT; PROGENITOR CELLS; FATE DECISIONS; IN-SITU; MOUSE; CANCER; DIFFERENTIATION; PLURIPOTENCY AB We present single-cell clustering using bifurcation analysis (SCUBA), a novel computational method for extracting lineage relationships from single-cell gene expression data and modeling the dynamic changes associated with cell differentiation. SCUBA draws techniques from nonlinear dynamics and stochastic differential equation theories, providing a systematic framework for modeling complex processes involving multilineage specifications. By applying SCUBA to analyze two complementary, publicly available datasets we successfully reconstructed the cellular hierarchy during early development of mouse embryos, modeled the dynamic changes in gene expression patterns, and predicted the effects of perturbing key transcriptional regulators on inducing lineage biases. The results were robust with respect to experimental platform differences between RT-PCR and RNA sequencing. We selectively tested our predictions in Nanog mutants and found good agreement between SCUBA predictions and the experimental data. We further extended the utility of SCUBA by developing a method to reconstruct missing temporal-order information from a typical single-cell dataset. Analysis of a hematopoietic dataset suggests that our method is effective for reconstructing gene expression dynamics during human B-cell development. In summary, SCUBA provides a useful single-cell data analysis tool that is well-suited for the investigation of developmental processes. C1 [Marco, Eugenio; Trippa, Lorenzo; Yuan, Guo-Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Marco, Eugenio; Trippa, Lorenzo; Yuan, Guo-Cheng] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Karp, Robert L.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Guo, Guoji] Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Guo, Guoji] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. [Robson, Paul] Natl Univ Singapore, Dept Biol Sci, Singapore 138672, Singapore. [Robson, Paul] Genome Inst Singapore, Singapore 138672, Singapore. [Hart, Adam H.] La Trobe Univ, Dept Genet, Melbourne, Vic 3086, Australia. RP Yuan, GC (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. EM gcyuan@jimmy.harvard.edu RI Robson, Paul/A-3464-2009; Hart, Adam/C-1196-2011 OI Robson, Paul/0000-0002-0191-3958; Hart, Adam/0000-0001-8129-3877 FU National Institutes of Health [R21HG006778]; Harvard Stem Cell Institute; Army Research Office FX We thank Drs. Kimberly Glass, Sidinh Luc, and Junhyong Kim for helpful discussions. G.-C.Y.'s research was supported by National Institutes of Health Grant R21HG006778 and grants from Harvard Stem Cell Institute and the Army Research Office. NR 60 TC 29 Z9 30 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 30 PY 2014 VL 111 IS 52 BP E5643 EP E5650 DI 10.1073/pnas.1408993111 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AY2UL UT WOS:000347444400009 PM 25512504 ER PT J AU Michaels, TM Horan, WP Ginger, EJ Martinovich, Z Pinkham, AE Smith, MJ AF Michaels, Tania M. Horan, William P. Ginger, Emily J. Martinovich, Zoran Pinkham, Amy E. Smith, Matthew J. TI Cognitive empathy contributes to poor social functioning in schizophrenia: Evidence from a new self-report measure of cognitive and affective empathy SO PSYCHIATRY RESEARCH LA English DT Article DE Schizophrenia; Empathy; Social functioning; Social cognition; QCAE ID EMOTION REGULATION; PSYCHOSIS; DEFICITS; METAANALYSIS; NEUROSCIENCE; SUPPRESSION; PERCEPTION; MECHANISMS; ABILITIES; ACCURACY AB Cognitive empathy impairments have been linked to poor social functioning in schizophrenia. However, prior studies primarily used self-reported empathy measures developed decades ago that are not well-aligned with contemporary models of empathy. We evaluated empathy and its relationship to social functioning in schizophrenia using the recently developed Questionnaire of Cognitive and Affective Empathy (QCAE). Schizophrenia (n=52) and healthy comparison (n=37) subjects completed the QCAE, Interpersonal Reactivity Index (IRI), and measures of neurocognition, symptoms, and social functioning. Between-group differences on the QCAE, and relationships between QCAE and IRI subscales, neurocognition, symptoms, and social functioning were examined. The schizophrenia group reported significantly lower cognitive empathy than comparison subjects, which was driven by low online simulation scores. Cognitive empathy explained significant variance in social functioning after accounting for neurocognition and symptoms. Group differences for affective empathy were variable; the schizophrenia group reported similar proximal responsivity, but elevated emotion contagion relative to comparison subjects. These findings bolster support for the presence and functional significance of impaired cognitive empathy in schizophrenia using a contemporary measure of empathy. Emerging evidence that some aspects of affective empathy may be unimpaired or hyper-responsive in schizophrenia and implications for the assessment and treatment of empathy in schizophrenia are discussed. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Michaels, Tania M.; Ginger, Emily J.; Martinovich, Zoran; Smith, Matthew J.] Northwestern Univ, Dept Psychiat & Behav Sci, Feinberg Sch Med, Chicago, IL 60611 USA. [Horan, William P.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Horan, William P.] VA Greater Los Angeles Healthcare Syst, VISN22, MIRECC, Los Angeles, CA USA. [Pinkham, Amy E.] Univ Texas Dallas, Sch Behav & Brain Sci, Richardson, TX 75083 USA. [Smith, Matthew J.] Northwestern Univ, Warren Wright Adolescent Ctr, Feinberg Sch Med, Chicago, IL 60611 USA. RP Smith, MJ (reprint author), Northwestern Univ, Dept Psychiat & Behav Sci, Feinberg Sch Med, Abbott Hall 13th Floor, Chicago, IL 60611 USA. EM matthewsmith@northwestem.edu OI Smith, Matthew/0000-0002-0079-1477 FU Department of Psychiatry and Behavioral Sciences at Northwestern University Feinberg School of Medicine; Warren Wright Adolescent Center at Northwestern Medicine's Stone Institute of Psychiatry FX We would like to acknowledge the research staff at the Northwestern University Schizophrenia Research Group-for study coordination and data collection, and our participants for volunteering their time. This work was funded by the Department of Psychiatry and Behavioral Sciences at Northwestern University Feinberg School of Medicine. Additional support for this study was provided by Warren Wright Adolescent Center at Northwestern Medicine's Stone Institute of Psychiatry. NR 68 TC 10 Z9 10 U1 5 U2 26 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 2014 VL 220 IS 3 BP 803 EP 810 DI 10.1016/j.psychres.2014.08.054 PG 8 WC Psychiatry SC Psychiatry GA AY1OD UT WOS:000347361300011 PM 25632418 ER PT J AU Bokman, CL Pasquale, LR Parrish, RK Lee, RK AF L. Bokman, Christine Pasquale, Louis R. Parrish, Richard K., II Lee, Richard K. TI Glaucoma Screening in the Haitian Afro-Caribbean Population of South Florida SO PLOS ONE LA English DT Article ID OPEN-ANGLE GLAUCOMA; DIABETES-MELLITUS; BARBADOS EYE; RISK-FACTORS; INTRAOCULAR-PRESSURE; UNITED-STATES; PREVALENCE; HYPERTENSION; VARIANTS; DISEASE AB Objective: To evaluate the presence of clinical signs consistent with suspected glaucoma in Haitian Afro-Caribbean individuals residing in South Florida who do not receive regular eye examinations. Design: Retrospective, cross-sectional study. Methods: SETTING: Community health center in the Little Haiti district of Miami, Florida. PATIENT POPULATION: We reviewed medical records and screening forms from five health screenings between October 2011 to October 2013 of 939 Afro-Caribbean individuals older than 18 years, who were never diagnosed with glaucoma or had an eye examination within the last ten years. PROCEDURES: Measurements of distance visual acuity (VA), intraocular eye pressure (IOP), central corneal thickness (CCT), cup-to-disc ratio (CDR), frequency doubling technology (FDT) perimeter visual field (VF). Main Outcome Measures: Proportion of glaucoma suspects, based on IOP greater than or equal to 24 mm Hg or CDR greater than or equal to 0.7 in either eye, and determinants of CDR and IOP. Results: One hundred ninety-one (25.5%) of 750 patients were identified as glaucoma suspects. Glaucoma suspects were common in both the youngest and oldest age groups (<40 years, 20.9%; 95% confidence interval [CI], 17.9-23.9; >70 years, 25.0%; 95% CI, 21.8-28.2) and higher in men than women less than 70 years; the reverse was true after 70 years. Among all patients, mean IOP was 19.2 +/- 4.5 mmHg, mean CDR was 0.37 +/- 0.17, and mean CCT was 532 +/- 37.1 mu m. In multiple linear stepwise regression analysis, determinates of increased CDR included increasing age (P = 0.004), lack of insurance (P = 0.019), and higher IOP (P<0.001), while increasing CDR (P<0.001) and thicker CCT (P<0.001) were associated with higher IOP. Conclusions: This first glaucoma survey in a U.S. Haitian Afro-Caribbean population indicates glaucoma suspect status is high across all age groups, and suggests glaucoma monitoring in people less than 40 years of age is indicated in this population. C1 [L. Bokman, Christine; Parrish, Richard K., II; Lee, Richard K.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA. [Pasquale, Louis R.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. [Pasquale, Louis R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. RP Lee, RK (reprint author), Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA. EM rlee@med.miami.edu FU Friends of the Congressional Glaucoma Caucus FX The authors received no specific funding for this work, although some of the vision screenings were funded by non-profit foundation the Friends of the Congressional Glaucoma Caucus (which is no longer active). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 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 30 PY 2014 VL 9 IS 12 AR e115942 DI 10.1371/journal.pone.0115942 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AX6YH UT WOS:000347063500041 PM 25549331 ER PT J AU Grayburn, PA Carabello, B Hung, J Gillam, LD Liang, D Mack, MJ McCarthy, PM Miller, DC Trento, A Siegel, RJ AF Grayburn, Paul A. Carabello, Blase Hung, Judy Gillam, Linda D. Liang, David Mack, Michael J. McCarthy, Patrick M. Miller, D. Craig Trento, Alfredo Siegel, Robert J. TI Defining "Severe" Secondary Mitral Regurgitation Emphasizing an Integrated Approach SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review DE echocardiography; guidelines; hemodynamics; mitral valve; mitral valve insufficiency ID VENTRICULAR SYSTOLIC DYSFUNCTION; CARDIAC RESYNCHRONIZATION THERAPY; VENA CONTRACTA AREA; HEART-FAILURE; VALVE REPAIR; DOPPLER-ECHOCARDIOGRAPHY; DILATED CARDIOMYOPATHY; 3D ECHOCARDIOGRAPHY; MAGNETIC-RESONANCE; SURGICAL-TREATMENT AB Secondary mitral regurgitation (MR) is associated with poor outcomes, but its correction does not reverse the underlying left ventricular (LV) pathology or improve the prognosis. The recently published American Heart Association/American College of Cardiology guidelines on valvular heart disease generated considerable controversy by revising the definition of severe secondary MR from an effective regurgitant orifice area (EROA) of 0.4 to 0.2 cm(2), and from a regurgitant volume (RVol) of 60 to 30 ml. This paper reviews hydrodynamic determinants of MR severity, showing that EROA and RVol values associated with severe MR depend on LV volume. This explains disparities in the evidence associating a lower EROA threshold with suboptimal survival. Redefining MR severity purely on EROA or RVol may cause significant clinical problems. As the guidelines emphasize, defining severe MR requires careful integration of all echocardiographic and clinical data, as measurement of EROA is imprecise and poorly reproducible. (C) 2014 by the American College of Cardiology Foundation. C1 [Grayburn, Paul A.] Baylor Heart & Vasc Inst, Dallas, TX 75226 USA. [Grayburn, Paul A.] Heart Hosp Baylor Plano, Dept Internal Med, Plano, TX USA. [Carabello, Blase] Mt Sinai Sch Med, Dept Internal Med, New York, NY USA. [Hung, Judy] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Gillam, Linda D.] Morristown Med Ctr, Morristown, NJ USA. [Liang, David] Stanford Univ, Sch Med, Dept Internal Med, Stanford, CA 94305 USA. [Mack, Michael J.] Heart Hosp Baylor Plano, Dept Cardiothorac Surg, Plano, TX USA. [McCarthy, Patrick M.] Northwestern Univ, Feinberg Sch Med, Bluhm Cardiovasc Inst, Chicago, IL 60611 USA. [Miller, D. Craig] Stanford Univ, Sch Med, Dept Cardiovasc Surg, Stanford, CA 94305 USA. [Trento, Alfredo; Siegel, Robert J.] Cedars Sinai Heart Inst, Los Angeles, CA USA. RP Grayburn, PA (reprint author), Baylor Heart & Vasc Inst, 621 North Hall St,Suite H030, Dallas, TX 75226 USA. EM paulgr@baylorhealth.edu FU Abbott Vascular; Philips Healthcare; Medtronic FX Dr. Grayburn has received grant support from Abbott Vascular and Medtronic; has served as a consultant for Abbott Vascular, Tendyne, and Bracco Diagnostics; and has had Echo Core Lab contracts for ValTech Cardio, Guided Delivery Systems, and Tendyne. Dr. Gillam has had Core Lab Research contracts for Edwards Lifesciences and Medtronic. Dr. Liang serves on the medical advisory board for and has received research support from Philips Healthcare. Dr. McCarthy has served as a consultant for Edwards Lifesciences; and is an inventor of IMR ETlogix. Dr. Miller has served on the PARTNER Executive Committee for Edwards Lifesciences; has served as a consultant for Medtronic CardioVascular Division and Abbott Vascular Structural Heart (MitraClip); has served on the scientific advisory board for GenTAC. Dr. Siegel has served as a speaker for Philips and Abbott Vascular. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Gerald Maurer, MD, served as Guest Editor for this paper. NR 47 TC 27 Z9 27 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 30 PY 2014 VL 64 IS 25 BP 2792 EP 2801 DI 10.1016/j.jacc.2014.10.016 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AX1WT UT WOS:000346734900012 PM 25541133 ER PT J AU Lindqvist, D Mueller, S Mellon, SH Su, YL Epel, ES Reus, VI Rosser, R Mahan, L Mackin, RS Yang, TT Wolkowitz, OM AF Lindqvist, Daniel Mueller, Susanne Mellon, Synthia H. Su, Yali Epel, Elissa S. Reus, Victor I. Rosser, Rebecca Mahan, Laura Mackin, R. Scott Yang, Tony T. Wolkowitz, Owen M. TI Peripheral antioxidant markers are associated with total hippocampal and CA3/dentate gyrus volume in MDD and healthy controls-preliminary findings SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Oxidative Stress; Glutathione; Vitamin C; Hippocampus; Subfields; Aging ID MAJOR DEPRESSIVE DISORDER; OXIDATIVE STRESS; PSYCHIATRIC-DISORDERS; ALZHEIMERS-DISEASE; ASCORBIC-ACID; GLUTATHIONE; BRAIN; NEURONS; IMPAIRMENT; DEFICIENCY AB Several psychiatric disorders, including major depressive disorder (MDD), are associated with increased blood markers of oxidative stress. The relevance of this to the oxidation-sensitive hippocampus (DC) is unknown. We investigated the relationship between peripheral oxidative stress markers and HC volume in unmedicated individuals with MDD (n = 16) and healthy controls (n = 19). To conserve power, our primary analysis was carried out in the combined group of subjects, and secondary analyses examined each group separately. Oxidative stress markers (oxidized glutathione (GSSG)) and antioxidants (reduced glutathione (GSH), glutathione peroxidase (Gpx), and Vitamin C) were assessed, and a "total net antioxidant score" was calculated. 4-T MRI estimated total HC volume and HC subfield (CA1, CAl-CA2 transition zone, subiculum and CA3/dentate gyms [CA3&DG]) volumes. Across groups, the antioxidant score was significantly and positively correlated with total HC volume and CA3&DG subfield volume (normalized to total intracranial volume), adjusting for age and sex. Similar relationships were observed in each individual group but missed statistical significance, likely due to type II errors, with the exception of a significant correlation between the antioxidant score and CA3&DG volume in the MDD group. These preliminary data are consistent with oxidative stress being associated with smaller total HC and CA3&DG subfield volumes. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Lindqvist, Daniel; Epel, Elissa S.; Reus, Victor I.; Rosser, Rebecca; Mahan, Laura; Mackin, R. Scott; Yang, Tony T.; Wolkowitz, Owen M.] Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94143 USA. [Lindqvist, Daniel] Lund Univ, Dept Clin Sci, Sect Psychiat, SE-22185 Lund, Sweden. [Mueller, Susanne] Univ Calif San Francisco, Sch Med, Dept Radiol, San Francisco, CA 94143 USA. [Mueller, Susanne; Mackin, R. Scott] San Francisco Vet Adm Med Ctr, San Francisco, CA USA. [Mellon, Synthia H.] Univ Calif San Francisco, Sch Med, Dept OB GYN & Reprod Sci, San Francisco, CA 94143 USA. [Su, Yali] Silver Creek Technol, Gilbert, AZ USA. RP Lindqvist, D (reprint author), Lund Univ, Dept Clin Sci, Sect Psychiat, Baravagen 1, SE-22185 Lund, Sweden. EM Daniel.Lindqvist@med.lu.se RI reus, victor/I-7923-2015 OI reus, victor/0000-0002-8193-5697 FU NIMH [RO1 MH083784]; Swedish Society of Medicine [SLS-244821]; Sjobring Foundation; OM Persson Foundation; province of Scania (Sweden) state grants (ALF); National Center for Research Resources; National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI [UL1 RR024131]; O'Shaughnessy Foundation; Tinberg family; [R01-NS31966]; [K08 (MH081065)]; [R01 (0977669)] FX This project was funded by NIMH Grant 1 RO1 MH083784 (co-Pl's: OMW, SHM and ESE), and by donations from the O'Shaughnessy Foundation and the Tinberg family. DL received post-doctoral grants from the Swedish Society of Medicine (SLS-244821), the Sjobring Foundation, the OM Persson Foundation and the province of Scania (Sweden) state grants (ALF).; SM has the following funding: R01-NS31966.; RSM has the following funding: K08 (MH081065) and R01 (0977669).; This project was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant Number UL1 RR024131. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. NR 39 TC 6 Z9 6 U1 0 U2 11 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 2014 VL 224 IS 3 BP 168 EP 174 DI 10.1016/j.pscychresns.2014.09.002 PG 7 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AU3QG UT WOS:000345527900004 PM 25266915 ER PT J AU Deckersbach, T Chou, T Britton, JC Carlson, LE Reese, HE Siev, J Scahill, L Piacentini, JC Woods, DW Walkup, JT Peterson, AL Dougherty, DD Wilhelm, S AF Deckersbach, Thilo Chou, Tina Britton, Jennifer C. Carlson, Lindsay E. Reese, Hannah E. Siev, Jedidiah Scahill, Lawrence Piacentini, John C. Woods, Douglas W. Walkup, John T. Peterson, Alan L. Dougherty, Darin D. Wilhelm, Sabine TI Neural correlates of behavior therapy for Tourette's disorder SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Behavior therapy; Habit reversal; Tourette's disorder; Neuroimaging ID OBSESSIVE-COMPULSIVE DISORDER; RANDOMIZED CONTROLLED-TRIAL; FUNCTIONAL MRI; HABIT REVERSAL; SUPPORTIVE PSYCHOTHERAPY; PREFRONTAL CORTEX; MOTOR INHIBITION; TIC DISORDERS; SCALE; ACTIVATION AB Tourette's disorder, also called Tourette syndrome (TS), is characterized by motor and vocal tics that can cause significant impairment in daily functioning. Tics are believed to be due to failed inhibition of both associative and motor cortico-striato-thalamo-cortical pathways. Comprehensive Behavioral Intervention for Tics (CBIT), which is an extension of Habit Reversal Therapy (HRT), teaches patients to become more aware of sensations that reliably precede tics (premonitory urges) and to initiate competing movements that inhibit the occurrence of tics. In this study, we used functional magnetic resonance imaging (MARI) to investigate the neural changes associated with CBIT treatment in subjects with TS. Eight subjects with TS were matched with eight healthy controls in gender, education, age, and handedness. Subjects completed the Visuospatial Priming (VSP) task, a measure of response inhibition, during fMRI scanning before and after CBIT treatment (or waiting period for controls). For TS subjects, we found a significant decrease in striatal (putamen) activation from pre- to post-treatment. Change in VSP task-related activation from pre- to post-treatment in Broclmann's area 47 (the inferior frontal gyrus) was negatively correlated with changes in tic severity. CBIT may promote normalization of aberrant cortico-striato-thalamo-cortical associative and motor pathways in individuals with TS.(C)2014 Elsevier Ireland Ltd. All rights reserved. C1 [Deckersbach, Thilo; Chou, Tina; Carlson, Lindsay E.; Reese, Hannah E.; Dougherty, Darin D.; Wilhelm, Sabine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Deckersbach, Thilo; Chou, Tina; Carlson, Lindsay E.; Reese, Hannah E.; Dougherty, Darin D.; Wilhelm, Sabine] Harvard Univ, Sch Med, Boston, MA USA. [Chou, Tina] Harvard Univ, Cambridge, MA 02138 USA. [Britton, Jennifer C.] Univ Miami, Coral Gables, FL 33124 USA. [Siev, Jedidiah] Nova Southeastern Univ, Ft Lauderdale, FL USA. [Scahill, Lawrence] Emory Univ, Atlanta, GA 30322 USA. [Piacentini, John C.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Woods, Douglas W.] Texas A&M Univ, College Stn, TX USA. [Walkup, John T.] Weill Cornell Med Coll, New York, NY USA. [Walkup, John T.] New York Presbyterian Hosp, New York, NY USA. [Peterson, Alan L.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Deckersbach, T (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM tdeckersbach@partners.org FU Tourette Syndrome Association; Intramural Research Program of the National Institute of Mental Health [ROO MH091183] FX The research reported in this manuscript was funded by a Tourette Syndrome Association grant to Dr, T. Deckersbach. This research was supported in part by the Intramural Research Program of the National Institute of Mental Health to Dr. J. Britton (Grant number ROO MH091183), NR 35 TC 7 Z9 8 U1 3 U2 23 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 2014 VL 224 IS 3 BP 269 EP 274 DI 10.1016/j.pscycliresiis.2014.09.003 PG 6 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AU3QG UT WOS:000345527900017 PM 25444535 ER PT J AU Michels, L Schulte-Vels, T Schick, M O'Gorman, RL Zeffiro, T Hasler, G Mueller-Pfeiffer, C AF Michels, Lars Schulte-Vels, Thomas Schick, Matthis O'Gorman, Ruth L. Zeffiro, Thomas Hasler, Gregor Mueller-Pfeiffer, Christoph TI Prefrontal GABA and glutathione imbalance in posttraumatic stress disorder: Preliminary findings SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Proton magnetic resonance spectroscopy; Anterior cingulatc cortex; Dorsolateral prefrontal cortex; Gamma-amino-butyric acid (GABA); N-acetyl aspartate (NAA) ID BENZODIAZEPINE-RECEPTORS; IN-VIVO; OXIDATIVE STRESS; MEGA-PRESS; ANXIETY; CORTEX; VALIDATION; GLUTAMATE; PTSD; RAT AB Although posttraurnatic stress disorder (PTSD) is associated with a variety of structural and functional brain changes, the molecular pathophysiological mechanisms underlying these macroscopic alterations are unknown. Recent studies support the existence of an altered excitation inhibition balance in PTSD. Further, there is preliminary evidence from blood sample studies suggesting heightened oxidative stress in PTSD, potentially leading to neural damage through excessive brain levels of free radicals. In this study we investigated PTSD (n=12) and non-PTSD participants (n=17) using single-voxel proton magnetic resonance spectroscopy (MRS) in dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). We found significantly higher levels of y-amino butyric acid (GABA) (a primary inhibitory neurotransmitter) and glutathione (a marker for neuronal oxidative stress) in PTSD participants. Atypically high prefrontal inhibition as well as oxidative stress may be involved in the pathogenesis of PTSD. (C)2014 Elsevier Ireland Ltd. All rights reserved. C1 [Michels, Lars] Univ Zurich Hosp, Inst Neuroradiol, CH-8091 Zurich, Switzerland. [Schulte-Vels, Thomas; Schick, Matthis; Mueller-Pfeiffer, Christoph] Univ Zurich Hosp, Dept Psychiat & Psychotherapy, CH-8091 Zurich, Switzerland. [O'Gorman, Ruth L.] Univ Zurich Hosp, Ctr MR Res, CH-8091 Zurich, Switzerland. [Zeffiro, Thomas] Massachusetts Gen Hosp, Neural Syst Grp, Boston, MA 02114 USA. [Hasler, Gregor] Univ Bern, Psychiat Univ Hosp, Bern, Switzerland. [Mueller-Pfeiffer, Christoph] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Mueller-Pfeiffer, Christoph] Harvard Univ, Sch Med, Boston, MA USA. [Mueller-Pfeiffer, Christoph] Psychiat Serv County St Gallen North, Ctr Educ & Res COEUR, Wil, Switzerland. RP Michels, L (reprint author), Univ Zurich Hosp, Inst Neuroradiol, CH-8091 Zurich, Switzerland. EM lars.michels@usz.ch RI Hasler, Gregor/E-4845-2012; OI Hasler, Gregor/0000-0002-8311-0138; O'Gorman, Ruth/0000-0001-5932-7786 NR 55 TC 13 Z9 14 U1 3 U2 13 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 2014 VL 224 IS 3 BP 288 EP 295 DI 10.1016/j.pscychresns.2014.09.007 PG 8 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AU3QG UT WOS:000345527900020 PM 25448399 ER PT J AU Ho, HP Rathod, P Louis, M Tada, CK Rahaman, S Mark, KJ Leng, J Dana, D Kumar, S Lichterfeld, M Chang, EJ AF Ho, Hsin-Pin Rathod, Pratikkumar Louis, Marissa Tada, Christine K. Rahaman, Sherida Mark, Kevin J. Leng, Jin Dana, Dibyendu Kumar, Sanjai Lichterfeld, Mathias Chang, Emmanuel J. TI Studies on quantitative phosphopeptide analysis bymatrix-assisted laser desorption/ionization mass spectrometry without label, chromatography or calibration curves SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID CYCLIN-DEPENDENT KINASES; PROTEIN-KINASE; PROTEOMICS; INHIBITORS; QUANTIFICATION; BIOMARKERS; DISCOVERY; MALDI; SILAC; MS AB RATIONALEMatrix-assisted laser desorption/ionization (MALDI) mass spectrometry combined with isotope labeling methods are effective for protein and peptide quantification, but limited in their multiplexing capacity, cost-effectiveness and dynamic range. This study investigates MALDI-MS-based quantification of peptide phosphorylation without labeling, and aims to overcome the shot-to-shot variability of MALDI using a mathematical transformation and extended data acquisition times. METHODSA linear relationship between the reciprocal of phosphopeptide mole fraction and the reciprocal of phosphorylated-to-unphosphorylated signal ratio is derived, and evaluated experimentally using three separate phosphopeptide systems containing phosphorylated serine, threonine and tyrosine residues: mixtures of phosphopeptide and its des-phospho-analog with known stoichiometry measured by vacuum MALDI-linear ion trap mass spectrometry and fit to the linear model. The model is validated for quantifying in vitro phosphorylation assays with inhibition studies on Cdk2/cyclinA. RESULTSDynamic range of picomoles to femtomoles, good accuracy (deviations of 1.5-3.0% from expected values) and reproducibility (relative standard deviation (RSD)=4.3-6.3%) are achieved. Inhibition of cyclin-dependent kinase phosphorylation by the classical inhibitors olomoucine and r-roscovitine was evaluated and IC50 values found to be in agreement with reported literature values. These results, achieved with single-point calibration, without isotope or chromatography, compare favorably to those arrived at using isotope dilution (p >0.5 for accuracy). CONCLUSIONSThe mathematical relationship derived here can be applied to a method that we term Double Reciprocal Isotope-free Phosphopeptide Quantification (DRIP-Q), as a strategy for quantification of in vitro phosphorylation assays, the first MALDI-based, isotope- and calibration curve-free method of its type. These results also pave the way for further systematic studies investigating the effect of peptide composition and experimental conditions on quantitative, label-free MALDI. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Ho, Hsin-Pin; Rathod, Pratikkumar; Kumar, Sanjai; Chang, Emmanuel J.] CUNY, Grad Ctr, Dept Chem, New York, NY USA. [Ho, Hsin-Pin; Rathod, Pratikkumar; Louis, Marissa; Tada, Christine K.; Rahaman, Sherida; Mark, Kevin J.; Chang, Emmanuel J.] CUNY York Coll, Jamaica, NY 11451 USA. [Mark, Kevin J.] CUNY, Dept Nat Sci, LaGuardia Community Coll, Long Isl City, NY USA. [Leng, Jin; Lichterfeld, Mathias] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. [Leng, Jin; Lichterfeld, Mathias] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Dana, Dibyendu; Kumar, Sanjai] CUNY Queens Coll, Dept Chem & Biochem, Queens, NY USA. [Kumar, Sanjai; Chang, Emmanuel J.] CUNY, Grad Ctr, Dept Biochem, New York, NY USA. RP Chang, EJ (reprint author), CUNY York Coll, 94-20 Guy R Brewer Blvd, Jamaica, NY 11451 USA. EM echang@york.cuny.edu FU National Institutes of Health [AI093203, AI098487, SC2GM086343]; Clinical Scientist Development Award from the Doris Duke Charitable Foundation [2009034]; American Foundation for AIDS Research [108302-51-RGRL]; Professional Staff Congress - City University of New York FX The authors gratefully acknowledge Rinku Prithiani for technical assistance and the University of Utah DNA/peptide facility for peptide synthesis. ML is supported by the National Institutes of Health (AI093203 and AI098487), Clinical Scientist Development Award from the Doris Duke Charitable Foundation (grant 2009034), and American Foundation for AIDS Research (grant 108302-51-RGRL). EJC is supported by the National Institutes of Health (SC2GM086343) and Professional Staff Congress - City University of New York. NR 31 TC 4 Z9 4 U1 1 U2 42 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0951-4198 EI 1097-0231 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PD DEC 30 PY 2014 VL 28 IS 24 BP 2681 EP 2689 DI 10.1002/rcm.7063 PG 9 WC Biochemical Research Methods; Chemistry, Analytical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA AU0PL UT WOS:000345325700001 PM 25380489 ER PT J AU Yetisen, AK Montelongo, Y Farandos, NM Naydenova, I Lowe, CR Yun, SH AF Yetisen, Ali K. Montelongo, Yunuen Farandos, Nicholas M. Naydenova, Izabela Lowe, Christopher R. Yun, Seok Hyun TI Mechanism of multiple grating formation in high-energy recording of holographic sensors SO APPLIED PHYSICS LETTERS LA English DT Article ID NANOSTRUCTURES; POLYMER; DEVICES; SURFACE AB We report numerical analyses of Bragg diffraction by Denisyuk reflection holograms recorded by a high-energy pulsed laser. An intensity threshold must be passed to pattern a multilayer reflection and transmission hologram, which exhibits a nonlinear fringe structure. Numerical evaluations are provided for the laser light intensity, readout diffraction offset angle, transmission of the layer, and thickness of the polymer matrix during hologram recording. A non-sinusoidal surface pattern is formed at the top of the multilayer structure, and its effect on the diffraction properties of the structure becomes significant when the recording tilt angle is increased. Experimental results show that the angle of the diffracted light increases nonlinearly according to the tilt geometry in grating formation. (C) 2014 AIP Publishing LLC. C1 [Yetisen, Ali K.; Yun, Seok Hyun] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Yetisen, Ali K.; Yun, Seok Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Montelongo, Yunuen] Univ Cambridge, Elect Engn Div, Dept Engn, Cambridge CB3 0FA, England. [Farandos, Nicholas M.] Univ London Imperial Coll Sci Technol & Med, Dept Chem Engn, London SW7 2AZ, England. [Naydenova, Izabela] Dublin Inst Technol, Ctr Ind & Engn Opt, Sch Phys, Coll Sci & Hlth, Dublin 8, Ireland. [Lowe, Christopher R.] Univ Cambridge, Dept Chem Engn & Biotechnol, Cambridge CB2 1QT, England. RP Yetisen, AK (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM ay283@cam.ac.uk RI Montelongo, Yunuen/H-4955-2012 OI Montelongo, Yunuen/0000-0002-1266-183X NR 31 TC 14 Z9 14 U1 5 U2 17 PU AMER INST PHYSICS PI MELVILLE PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA SN 0003-6951 EI 1077-3118 J9 APPL PHYS LETT JI Appl. Phys. Lett. PD DEC 29 PY 2014 VL 105 IS 26 AR 261106 DI 10.1063/1.4905352 PG 5 WC Physics, Applied SC Physics GA AX8PO UT WOS:000347171300006 ER EF